Heterocyclic Chemistry Vol 2

Heterocyclic Chemistry
Volume 2
A Specialist Periodical Report
Volume 2
A Review of the Literature Abstracted

between July 1979 and June 1980
Senior Reporters
H. Suschitzky and 0. Meth-Cohn Department of Chemistry and
Applied Chemistry, University of Salford
Reporters
G. V. Boyd Chelsea College, London
G. M . Brooke University of Durham
G.P. Ellis UWIST, Cardiff
S. Carter Queen Elizabeth College, London
G. W. H. Cheeseman Queen Elizabeth College, London
S. Gronowitz University of Lund, Sweden
P. A. Lowe University of Salford
T. J. Mason Lanchester Polytechnic, Coventry
J. M . Mellor University of Southampton
J. T. Sharp University of Edinburgh
R. C. Storr University of Liverpool
The Royal Society of Chemistry

Burlington House, London W I V OBN
British Library Cataloguing in Publication Data
Heterocyclic chemistry. - Vol. 2 . -

( A Specialist periodical report)
1. Heterocyclic compounds - Periodicals
I. Royal Society of Chemistry
547’.58’05 QD339
ISBN 0-85186-813-4
ISSN 0144-8773
Copyright @ 1981
The Royal Society of Chemistry
All Rights Reserved

No part of this book muy be reproduced or transmitted in any form
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In trod uc tion
Volume 2 of ‘Heterocyclic Chemistry’ covcrs original material abstracted from

Volumes 91 and 92 (i.e. July 1979 to June 1980) of Chemical Abstracts; i.e.,
material essentially published in 1978-9. The arrangement of the Chapters
follows the scheme adopted in Volume 1, and thus provides continuity and
hopefully facilitates searching by virtue of an extensive ‘Table of Contents‘. For
reasons of economy, our contributors had to keep their reviews within a strictly
defined number of pages and were, therefore, obliged to select only the more
significant advances in the field. We hope readers will agree that comprehen-
sibility has in no way suffered. The policy to illustrate as many reactions as
possible by formulae has been maintained, since we feel this to be essential for a
rapid understanding of the subject and for enabling the hard-pressed organic
chemist to browse through the book with least effort.
Our thanks go to authors for delivering manuscripts in good time for the earliest
possible publication and to the editorial staff of the Royal Society of Chemistry for
their invaluable help and advice.
H. SUSCHITZKY& 0. METH-COHN
Con tents
Chapter 1 Three-Membered Ring Systems 1

B y T. J. Mason
1 Oxirans 1
Preparation 1
Catalytic Oxidation of Alkenes, using Oxygen or
Oxygen-containing Gases 1
Oxidation of Alkenes by Peroxy-acids 3
Oxidation of Alkenes, using Peroxides 5
Halohydrin Cyclizations and Related Reactions 7
Synthesis tlia Attack of a Carbanion on the Carbonyl
Group of Aldehydes and Ketones 8
Synthesis of Chiral Oxirans 9
Synthesis and Reactivities of Aromatic Oxides 11
Miscellaneous Syntheses 12
Spectra and Theoretical Chemistry 14
Reactions with Electrophiles 15
Ring-opening 15
Cyclization 16
Nucleophilic Ring-opening Reactions 18
With Oxygen and Nitrogen Nucleophiles 18
With Carbanions 20
Reduction and Elimination Reactions 21
Photochemical and Thermal Reactions 23
Reactions with Organometallic Compounds 25
Miscellaneous Reactions 26
2 Oxirens 27
3 Aziridines 27
Preparation 28
Direct Insertion 28
Cyclization 29
Ring Contraction 30
vii
... Heterocyclic Chemistry
Vlll
Chiral Aziridines 31
Spectroscopic Studies 32
Reactions 33
Photochemical and Thermal 33
With Retention of the Aziridine Ring 34
Ring-opening to Acyclic Compounds 35
Formation of Other Ring Systems 36
4 Azirines 37
Preparation 38
Reactions 39
5 Thiirans 41
Preparation 42
Reactions 42
Chemistry of Thiiranium Ions 43
6 Thiirens 44
7 Diaziridines 45
8 Diazirines 46
9 Oxaziridines 47
Chapter 2 Four-Membered Ring Systems 51

By R. C.Storr
1 Reviews 51
2 Systems containing One Nitrogen Atom 51
Azetidines and Azetines 51
Azetidinones 5 3
3 Systems containing Two Nitrogen Atoms or One Nitrogen
and a Second Heteroatom 60
4 Systems containing One Oxygen Atom 61
Oxetans 61
2 Oxetanones (p-Lactones) 63
5 Systems containing Two Oxygen Atoms 66
Dioxetans 66
6 Systems containing Sulphur 69
7 Miscellaneous Four-Membered Rings 71
Contents ix
Chapter 3 Five-Membered Ring Systems 73

By G. V. Boyd, P. A. Lowe, and S . Gronowitz
Part 1 Thiophens and their Selenium and Tellurium Analogues 73

By S. Gronowitz
1 General 73
2 Monocyclic Thiophens 73
Synthesis by Ring-closure Reactions 73
Synthesis from Other Rings 75
Physical Properties 76
Electrophilic Substitution Reactions 77
Nucleophilic Substitution Reactions 79
Organometallic Derivatives 81
Photochemistry 84
The Structure and Reactions of Hydroxy-, Mercapto-, and
Amino-thiophens 84
Various Reactions 86
Reactivities of Side-chains 87
Benzylic Reactivity 87
Reactions of Thiophen Aldehydes and Ketones 87
Reactions of Carboxy- and Cyano-thiophens 88
Various Reactions of the Side-chain 88
Reaction at Sulphur: Thiophen Dioxides 89
Di- and Tetra-hydrothiophens 90
Bi- and Poly-heterocycles 92
Naturally occurring Thiophens 92
Thiophen Analogues of Steroids 93
Thiophens of Pharmacological Interest 93
3 Benzothiophens and their Benzo-fused Systems 95
Synthesis of Benzo[b]thiophens 95
Substitution Reactions 96
Reactions of the Side-chain 96
Benzo[b]thiophen S-Oxides 97
Benzo[c]thiophens 97
D ibenzo t hiop hens 9 8
Pharmacologically Active Compounds 98
4 Thiophen Analogues of Polycyclic Aromatic Hydrocarbons 98
Analogues of Anthracene and Phenanthrene 98
Various Carbocyclic Fused Systems 98
X Heterocyclic Chemistry
5 Thiophens Fused to Five-Membered Heteroaromatic Rings 99

Thiophen- and Pyrrole-fused Thiophens
and Related Compounds 99
Pyrazole, Thiazole-, and Isothiazole-fused Thiophens
and Related Systems 99
6 Thiophens Fused to Six-Membered Heteroaromatic Rings 101
Analogues of Quinoline 101
Analogues of Isoquinoline 102
Pyrimidine-fused Systems 102
Miscellaneous Fused Systems 102
7 Selenophens and Tellurophens 103
Monocyclic Selenophens 103
Condensed Selenophens 103
Tellurophens 104
Part Ii Systems containing Nitrogen and Sulphur, Selenium,

or Tel Iu ri u m 104
By P. A. Lowe
1 Introduction and Reviews 104

2 Isothiazoles 105
Synthesis 105
From 1,2-Dithiolans (Type C) 105
From 0-Aminocrotonates (Type C) 105
From Benzothiazolyldithioazetidinone (Type C) 105
From y-Amino-alkyl Thioethers (Type C ) 106
From Thione S-Imides (Type D) 106
From 0-Aryl-oximes and Alkanethiols (Type E) 106
Reactions 106
Photolytic 106
Ring-expansion 106
Ring-opening 107
3 1,2-Benzisothiazoles 107
Synthesis 107
Reactions 107
4 1,2-Benzisoselenazoles 108
5 2,l-Benzisothiazoles 109
6 Other Condensed Ring Systems incorporating Isothiazole 109
Heteropentalenes 109
Contents xi
Isothiazolo[5,4-b]pyridines 1 10
Isothiazolo[3,4-c]pyridazines 110
Isothiazolo[3,4-d]pyridines 110
7 Thiazoles 110
Synthesis 110
Type A (S-C-N + C-C) 110
Type C (C-C-N-C + S) 110
Type F (C-N-C-S + C) 111
Type K (C-C-N-C-S) 111
Synthesis of Meso-ionic Thiazoles 111
Chemical Properties 112
Reactions of 2-Amino-thiazoles 112
Reactions of Thiazolium Salts 112
Reactions of Meso-ionic Thiazoles 11 3
8 A2-Thiazolines 114
Synthesis 114
Type K (C-C-N-C-S) 114
9 A3-Thiazolines 115
10 A*-Thiazolines 116
11 Thiazolidines 116
Synthesis 116
Type B (C-C-N + C-S) 117
Type D (C-C-S + C-N) 117
Type E (N-C-C-S + C) 117
Miscellaneous 117
Rhodanine and Isorhodanine 119
12 Selenazoles 119
13 Benzothiazoles 119
Synthesis 119
From o-Amino-benzenethiols (Type A; S-C,H,-N + C) 119
Type B (C,H,-N-C-S) 120
Type D (S-C,H,-N-C) 121
Type G (C,H,-S-C-N) 121
x11 Heterocyclic Chemistry

Substitution Reactions 122
Alkylation Reactions 123
Reactions of Benzothiazolium Salts 123
Rearrangements 124
14 Condensed Ring Systems incorporating Thiazole 124
Structures comprising Two Five-Membered Rings ( 5 , 5 ) 124
Thiazolo[3,2-d]tetrazoles [CN4-C3NS] 124
Thiazolo[2,3-c]thiazoles [C2N3-C3NS] 125
Thiazolo[2,3 -b]- 1,3,4-thiadiazoles [C2N2S-C,NS] 125
Thiazolo-[2,3-b]- and - [5,4 -dl -thiazoles
[C,NS-C,NS] 125
Imidazo[2,1 -b]thiazoles [C3NS-C3N2] 125
Pyrrolo[2,3 - dlthiazoles [C,NS-C,N] 126
Structures comprising One Five-Membered and One
Six-Membered Ring (5,6) 126
Thiazolo[3,2-c][1,2,4,6]thiatriazine [C3NS-C2N3S] 126
Thiazolo-[3,2-b]- and -[3,2-c]-[ 1,2,4]triazines
[C,NS-C 3N3] 126
Thiazolo[5,4-~]pyridazines[C3NS-C4N2] 127
Thiazolo[3,2-~]pyrirnidines[C3NS-C4N2] 127
Thiazolo-[4,5-4- and -[5,4 -d]-pyrimidines
[C,NS-C4N2] 127
Thiazolo[4,5 -e]oxazines [C,NS-C4NO] 127
Thiazolo[3,2-~]pyridines[C,NS-C,N] 127
Thiazolo[4,5 -b]pyridines [C3NS-C,N] 128
Thiazolo[4,5-d]pyrans [C3NS-C50] 129
Structures comprising One Five-Membered Ring and One
Seven-Membered Ring (5,7) 129
Thiazolo-[3,2-a]- and -[4,5 -el-diazepines [C,NS-CsN2] 129
Structures comprising Two Five-Membered Rings and One
Six-Membered Ring (5,5,6) 129
1,2,4-Triazolo[ 3,4 - b]benzot hiazole [C2N3-C3NS-c6] 129
Benzo[2,3-d:5,6-d’]bisthiazoles[C3NS-C3NS-C6] 129
Thiazolo[3,2-a]benzimidazoles [C3NS-C3N,-C6] 129
Imidazo[2,1-b]benzothiazoles[C3NS-C3N2-C6] 130
Thiazolo[3,2-u]indoles [C3NS-C4N-C6] 130
Pyrrolo[2,l-b]benzothiazoles[C3NS-C4N-C,] 130
Structures comprising Two Five-Membered Rings and
One Seven-Membered Ring (5,5,7) 131
Azuleno[2,1-d]thiazoles [C,NS-C,-C,] 131
4-Aza-azuleno[2,3-d]thiazoles[C,NS-C,N-C,] 131
...
Conten ts Xlll
Structures comprising one Five-Membered Ring and Two

Six-Membered Rings (5,6,6) 131
1,3,5-Triazino[2,1-b]benzothiazole [C,NS-C,N,-CJ 131
8-Thia-l,4-diazacyc1[3.3.2]azines [C?NS-C4N2-C4N2] 131
Thiazolo[5,4-b]naphthyridines [C3NS-CSN-CSN] 132
Pyrimido[2,1 -h]benzothiazoles [C3NS-C,N2-C6] 1 32
Thiazolo-[2,3 -h]-, -[3,2-a]-, and -[3,2-c]-quinazolines
[C?NS-C4N,-C,] 132
Pyrido[2,l-b]benzothiazoles [C3NS-CsN-C6] 133
Thiazolo[3,2-~]quinolines[C,NS-CsN-C6] 133
Thiazolo[2,3-a]isoquinolines [C,NS-CsN-C6] 133
Other Condensed Systems incorporating Thiazole 133
15 Thiadiazoles and Selenadiazoles 134

1,2,3-Thiadiazoles 134
Synthesis 134
1,2,3-Selenadiazoles 135
Synthesis 135
Properties 136
Synthesis 137
Properties 138
Condensed 1,3,4-Thiadiazoles 138
Synthesis 140
Reactions 140
2,1,3-Benzothiadiazoles 140
Condensed 1,2,5-Thiadiazoles 140
2,1,3-Benzoselenadiazoles 141
16 Dithiazoles and Diselenazoles 141

1,2,3-Dithiazoles 141
1,2,4-Diselenazoles 143
17 Oxathiazoles 143
1,2,3-Oxathiazoles 143
1,3,5 -0xa thiazoles 144
18 Miscellaneous Ring Systems 144

1,2,4-Thiatellurazoles 144
1,2,3,4-Thiatriazoles 144
xiv Heterocyclic Chemistry
1,2,3,5-Thiatriazoles 144
1,2,3,5-Dithiadiazoles 145
1,3,2,4-Dithiadiazoles 145
1,3,4,2-Thiadiazaphospholes 145
Part Ill Other Five-Membered Ring Systems 145

B y G . V. Boyd
1 Introduction 145
2 Reviews 146
3 Systems with One Heteroatom, and their Benzo-
analogues 146
Furans 146
Formation 146
Reactions 148
Benzofurans and Other Anrielated Furans 152
Pyrroles 156
Formation 156
Reactions 157
Indoles 160
Formation 160
Reactions 164
Isoindoles 168
4 Systems containing Two Identical Heteroatoms 168
Dioxoles 168
1,2-Dithioles 169
1,3-Dithioles 170
Tetrathiafulvalenes 172
Pyrazoles 173
Formation 173
Reactions 175
Indazoles 180
Imidazoles 180
Formation 180
Reactions 182
Benzimidazoles 183
5 Systems containing Two Different Heteroatoms 184
Oxathioles and Oxaselenoles 184
Isoxazoles 186
Formation 186
Reactions 188
2,l -Benzisoxazoles 190
Contents xv
Oxazoles 191
Formation 191
Reactions 192
Benzoxazoles 193
Other Systems 193
6 Systems containing Three Identical Heteroatoms 194
1,2,3-Triazoles and Benzotriazoles 194
Formation 194
Reactions 194
1,2,4-Triazoles 196
7 Other Systems containing Three Heteroatoms 197
Oxadiazoles 197
1,2,3-Oxadiazoles 197
Phosphorus Compounds 200
Miscellaneous Other Compounds 202
8 Systems containing Four Heteroatoms 203
Tetrazoles 203
Oxatriazoles and a Triazaphosphole 204
9 Compounds containing Two Fused Five-Membered
Rings ( 5 3 ) 204
Hypervalent Sulphur Compounds and their Selenium and
Tellurium Analogues 204
Nitrogen Systems 205
Monoaza-compounds 205
Diaza-compounds 206
Triaza-compounds 207
Tetra- and Hexa-aza-compounds 207
Mixed Oxygen-Nitrogen Systems 208
A Phosphorus System 210
10 Compounds containing Fused Five- and Six-Membered

Rings (5,6) 210
Nitrogen Systems 210
Monoaza-compounds 2 10
Diaza-compounds 2 12
Triaza-compounds 214
Tetra-aza-compounds 2 14
Penta- and Hexa-aza-compounds 215
Mixed Oxygen-Nitrogen Systems 216
xvi Heterocyclic Chemistry
11 Compounds containing Fused Five- and Seven-Membered Rings

and Five- and Eight-Membered Rings [(5,7) and (5,S)l 218
12 Compounds containing Three or Four Fused Heterocyclic

Rings [(5,5,5), (5,5,6), (5,5,7), (5,6,7), and (5,5,5,6)1 220
Chapter 4 Six-Membered Ring Systems 223

By S. D. Carter, G. W. H. Cheeseman, and G. P. Ellis
Part I Systems containing Nitrogen 223

By S. D. Carter and G. W. H. Cheeseman
1 Introduction 223
2 Reviews 223
3 Azines and their Hydro- and Benzo-derivatives 224
Pyridines 224
Synthesis 224
Reactions 228
Reduced Pyridines 234
Quinoline, Isoquinoline, and their Benzo-
and Hydro-derivatives 240
4 Diazines and their Reduced and Fused Derivatives 250
1,2-Diazines 250
1,3-Diazines 253
1,4-Diazines 259
5 Triazines and Tetrazines 263
6 Fused Systems containing One Five- and One
Six-Membered Ring: (5,6) 266
7 Fused Systems containing Two Six-Membered Rings (6,6) 270
8 Oxazines, Thiazines, and their Fused Derivatives 272
Oxazines and their Fused Derivatives 272
Thiazines and their Fused Derivatives 276
9 Other Oxygen- and Sulphur-containing Systems 279
Part II Other Six-Membered Ring Systems 283

By G. P. Ellis
1 Books and Reviews 283
Con tents xvii
2 Heterocycles containing One Oxygen Atom 283

Reduced Pyrans 283
Pyrans 285
2-Pyrones 286
3-Pyrones 287
4-Pyrones 287
Pyrylium Salts 289
3 Heterocycles containing One Sulphur Atom 290

Reduced Thiopyrans 290
Thiopyrans 292
4 Fused Heterocycles containing One Oxygen or Sulphur Atom 293

Chromans 293
2 H- C h ro m e n es 2 96
4 H-C h rom e n es 2 97
Isochromenes 298
3-Chromanones 298
4-Chromanones 298
Chromones 300
Th ioch ro m an s and T h iochr om o n es 302
Flavans 303
Isoflavans and Isoflavylium Salts 303
Flavanones 304
Isoflavanones 306
Flavones 306
Isoflavones 309
Thioflavans and Thioflavones 3 10
Dihydroisocoumarins 3 10
Coumarins 3 11
Isocoumarins and Related Compounds 315
Xanthenes 315
Xanthones 317
Thioxanthenes 3 19
5 Heterocycles containing One Oxygen and One Sulphur Atom 320
6 Heterocycles containing Two Oxygen Atoms 321

1,3-Dioxans 321
1,3-Benzodioxins 322
1,4-Dioxans and 1,4-Benzodioxins 323
7 Heterocycles containing Two Sulphur Atoms 323

1,3-Dithians and 1,4-Dithians 323
xviii Heterocyclic Chemistry
8 Heterocycles containing an Oxygen Atom

in each of Two Rings 324
Synthesis 324
Properties and Reactions 326
Naturally Occurring Compounds 326
9 Heterocycles containing Oxygen and/or Sulphur Atoms
in each of Two or Three Rings 327
10 Oxygen-containing Spirans 329
11 Heterocycles containing Phosphorus (with or
without Oxygen) 329
12 Heterocycles containing Other Atoms 330
Chapter 5 Seven-Membered Ring Systems 33 1

B y J. T. Sharp
1 Introduction 331
2 Reviews 331
3 Azepines and Diazepines 331
Monocyclic Azepines 33 1
Formation 331
Reactions 333
Fused Azepines 334
Formation 334
Reactions 336
1,2-Diazepines 336
Formation 336
Reactions 339
1,3-Diazepines 341
1,4-Diazepines 342
Formation 342
Reactions and Properties 344
4 Oxepins and Dioxepins 346
Oxepins 346
Formation 346
Properties and Reactions 348
Dioxepins 349
5 Thiepins and Dithiepins 350
Thiepins 350
Dithiepins 352
Contents xix
6 Systems containing Two Different Heteroatoms 353
Oxazepines and Thiazepines 353
Other Systems 355
7 Systems containing Three Heteroatoms 356
Chapter 6 Eight-Membered and Larger Ring Systems 359

By G. M. Brooke
1 Eight-Membered Rings 359
One Heteroatom 359
Two Heteroatoms 359
2 Nine- and Ten-Membered Heterocycles 360
3 Macrocycles 362
Systems containing Nitrogen as the only Heteroatom 362
One Nitrogen Atom 362
Four Nitrogen Atoms 363
Systems containing Nitrogen and Other Heteroatoms 364
Systems containing Heteroatoms Other than Nitrogen 364
Crown Ethers and Related Compounds 367
Synthesis 367
Effects on Chemical Reactions 368
Reactions of the Macrocyclic Rings of Crown Ethers
and Related Compounds 371
Formation of Host-Guest Complexes 372
Chapter 7 Bridged Systems 381

By J. M. Mellor
1 Introduction 381
2 Reviews 381
3 Physical Methods 382
X-Ray and Neutron Diffraction 382
Photoelectron Spectroscopy and Related Electro-
chemical Studies 384
Nuclear Magnetic Resonance Spectroscopy 384
Miscellaneous Methods 385
4 Systems containing Nitrogen 386
Synthesis 386
Cycloadditions 386
Cyclizations with Nucleophilic Nitrogen 392
xx Heterocyclic Chemistry
Other Cyclizations 394
Reactions 397
Bridged Azoalkanes 399
5 Systems containing Oxygen 401
Synthesis 401
Cycloadditions 401
Miscellaneous Syntheses 402
Bridged Peroxides 406
6 Systems containing Sulphur 407

Synthesis by Cycloaddition 407
Miscellaneous Syntheses and Reactions 407
7 Systems containing Other Heteroatoms 408
Author Index 41 1
Three-Membered Ring Systems
BY T. J. MASON
1 Oxirans
The interest of Eastern European chemists in oxirans has been evident for many
years, and from such sources have come a number of reviews on the production of
these important raw materials. While concentrating mainly on ethene and
propene one review deals more specifically with the types of hetero-
. ~ latest edition of the Kirk-
geneous catalysts employed in the p r o c e ~ s e s The
Othmer Encyclopedia contains an entry on epoxidation.'
An extensive article on the importance of chalcone oxides in flavonoid chem-
istry contains 346 references6 Other specialised reviews have appeared on the
chemistry of juvenile hormones (up to 1974),7 epoxy-sulphones,x and epoxy-
derivatives of dicyclopentadiene.'
'The important safety aspects of the use of oxiran in high-pressure bench-scale
experiments have been considered.'"
Preparation.-Catalytic Oxidation of Alkenes to Oxirans, using Oxygen or O x y -
gen-containing Gases. The mechanism for the conversion of the phenol (1)into
the epoxy-quinol (4) by molecular oxygen in Bu'OK-Bu'OH has been investi-
gated (Scheme l)." The first step is the formation of hydroperoxide ( 2 ) ,which is
converted into hydroperoxide (3) via a r-complex intermediate; the yield of (4)
increases with temperature.
' R. P. Kayumov and T. G . Khaimova, Neftepewrab. Neftekhim (Moscow),1979, 37 and 39 (Chem.

Abstr., 1979, 91, 157 519, 91 072).
W. Swodenk and H. Waldmann, Chem. UnsererZeit, 1978,12,65 (Chem. Abstr., 1979,91,74 385).
E. J. Mistrik, Petrochemia, 1979, 19, 35 (Chem. Abstr., 1979, 91, 9 1 414).
E. A. Mamedav, I. I. Sidorchuk, V. M. Negurenko, N. K. Kholodova, and L. V. Oleinikova,
Deposited Document, 1978, VINITI 2099 (Chem. Abslr., 1979,91,210 819).
' J . T. Lutz, Jr., in 'Kirk-Othmer Encyclopedia of Chemistry and Technology', 3rd edn., ed. M.
Grayson and D . Eckroth, Wiley, New York, 1980, Vol. 9, p. 251.
G . Litkei, Recent Dev. Chem. Nat. Carbon Compd., 1979,9, 293.
W. Sobotka and R. Sterzycki, Pr. Nauk. Inst. Chem. O r g . Fiz. Politech. Wroclaw., 1979, 14,5 (Chem.
Abstr. 1979, 91, 175 084).
T. Durst, in 'Topics in Organic Sulphur Chemistry' (Plenary Lecture at the 8th International
Symposium) ed. M. Tisler, University Press, Ljubljana, Yugoslavia, 1978, p. 29.
E. M. Savrasova and V. N. Orekhov, Vestn. Khar'k. Politekh. Inst., 1977, 135, 15 (Chem. Abstr.,
1979, 91, 157 523).
lo G . A. Pogany, Chrm. Ind. (London), 1979, 16.
" A. Nishinaga, T. Shimizu, and T. Matsuura, J. Org. Chem., 1979, 44, 2983.
1
2 Heterocyclic Chemistry
(1) (2) (3)

Reagents: i, 0, bubbled through Bu'OK in Bu'OH-hexane
Scheme 1
Photo-oxygenation of cyclohepta-3,5-dienone that is sensitized with tetra-

phenylporphyrin leads initially to the 3,6-endoperoxide; this, on reduction with
di-imide, gives ( S ) , from which (6) and (7)were obtained, uia photolysis at 300 nm
in CDCI, and subsequent deoxygenation with PPh, in CH2CI2,at 0 "C, respect-
ively." Photo-oxidation of 3-methylfuran in CH,C12 at 0 "C, with methylene blue
as the sensitizer, led directly to the epoxy-ketones (8) and (9),together with some
diepoxide.l 3
0 0
Dye-sensitized oxygenation of vinylsilanes yields p -silylated allylic alcohols uia

epoxysilane intermediates and provides a new synthesis of allylic alcohols from
saturated ketones (Scheme 2).14Thevinylsilanes (10; R = H) and (10; R = Me),
prepared from the corresponding cyclohexanone benzenesulphonylhydrazone,
react with singlet O2 to give the intermediates (11) (not isolated); these open
regiospecifically to (12), from which (13) may be obtained on reaction with
p-j]
Bun4" F-. Calculations indicate the possible role of silicon in directing the
opening of the oxiran ring.
SiMe, SiMe, SiMe,
JRf -3
I ----*
II y J 0 H --* R O O ,
(10) (11) (12) (13)

Reagents: i, singlet 0,; ii, NaBH,; iii, Bu",N' F -
Scheme 2
The kinetics of oxidation of ethene at 490-620 K, using Ag catalysts suppor-

ted on pumice, have been r e p ~ r t e d . Total
'~ oxidation to CO, and H,O accom-
panies formation of oxiran, apparently with similar activation energies. Ethene
W. Adam and I. Erden, Tetrahedron Lett., 1979, 1975.
" W. Grimminger and W. Kraus, Liehigs Ann. Chem., 1979, 1571.
W. E. Fristad and T. R. Bailey, J. A m . Chem. SOC.,1979,101, 4420.
'* H. R. Dettwiler, A. Baiker, and W. Richarz, Helu. Chim.Acfa, 1979, 62, 1689.
Three-Membered Ring Systems 3
has also been oxidized, using complex catalysts derived from silver carboxylates
and heterocyclic compounds, 78.5 n/' selectivity being obtained using the catalyst
from silver acetate and 2-rnethyl-2-0xazoline.~~ Epichlorohydrin may, however,
be obtained directly from ally1 chloride in the liquid phase, using simply silver
nitrate in dimethyl phthalate."
The epoxy-alcohol (15) (76"/0)was obtained from (14), using the cyclo-
pentadienyl-vanadium catalyst [(C,H,)V(CO),] in solution at 50 OC.I8 Under
similar reaction conditions, a catalyst prepared by exchange of V4+and Cu" with
an Na-X-zeolite resin furnished a mixture of (15) and (16)in 46% and 40% yields
respectively. l 9
The 1 : 1 complex formed between ZnC12 and tetramethyl-2-tetrazene reacts

with cyclo-octene and oxygen to give solely the oxiran, whereas with styrene the
reaction goes further, the intermediate oxiran ring being opened regiospecifically
to produce the amino-alcohol PhCH(OH)CH2NMe2.2"
Oxidation of A lkenes to Oxirans by Peroxy-acids. The mechanism of the reaction
of rn -chloroperbenzoic acid with double bonds has been investigated through a
study of the epoxidation of a series of cycloalkenes (of ring sizes 5 , 6 , 7 , 8 , and 12)
and substituted cyclohexenes.21 The second-order rate constants were deter-
mined in CHCI, at O-3O0C, and the data support a 1,3-dipolar cycloaddition
reaction.
Factors that affect the stereoselectivity of epoxidations with peroxy-acids have
been probed. A remarkable change in selectivity has been observed when a
p-carbonyl group is introduced into the lanost-9(1l)-ene skeleton.'* While (17;
R = H) yields only a-epoxide on treatment with 3-C1C6H4CO3H,the presence
of the carbonyl group in (17; R2 = 0)produces a ratio of 0- : a-epoxides of 3 : 1
in CHCI,, which falls to 1 : 1 in more polar solvents. Undoubtedly there must be
considerable steric influence in this reaction, but it is thought that the carbonyl
group acts largely through a polar effect, reducing the rate of epoxidation of (17;
R = H) by a factor of 300. Mono-epoxidation of the substituted cyclohexa-1,4-
dienes (18; R' = Me, R2 = C 0 2 M e or C H 2 0 H ) and (18; R' = H, R2 =
C02Me).with 3-CIC6H4C0,H demonstrates a predominant steric control of
epoxidation23rather than, as previously suggested, a cis-directing effect by allylic
methoxycarbonyl groups.24 The diene (18; R' = Me, R2 = C02Me) gave a
l6 J. M. Cognion and J. Kervennal, Eur. Pat. Appl. 5388 (Chern. Abstr., 1980, 92, 163 829).
Sh. K. Kyazimov, A. S. Rzaeva, G. Z. Ponomareva, and F. M. Alieva, Neftekhimiya, 1979,19,458
(Chem. Abstr., 1979, 91, 91 417).
l 8 J. E. Lyons, Can. P. 1 060 032 (Chern. Abstr., 1980, 92,22 371).
l9 J. E. Lyons, U.S. P. 4 182 722 (Chem. Abstr., 1980,92, 198 248).
'"C. J. Michejda, D. H . Campbell, and D. Sieh, Colloq. Inf. C.N.R.S.,1977 (publ. 19781,278, (Radicaux
Libres Org.), 521 (Chern. Abstr., 1979, 91, 174 428).
'' R. R . Cetina and C. H. Solis, Reu. Latinoam. Quim., 1979,10, 140 (Chem. Abstr., 1980,92,75445).
22 Z. Paryzek, J. Chem. Soc., Perkin Trans. 1, 1978, 329.
'' T. Mah, H. M. Sirat, and E. J. Thomas, J. Chem. SOC., Perkin Trans. I, 1979, 2255.
24 S. A. Cerefice and E. K. Fields, J: Org. Chem., 1976, 41, 3 5 5 .
55 : 45 mixture of epoxides, with the predominant isomer having the oxiran ring
cis to the methoxycarbonyl group. The product distribution reflects the slightly
smaller bulk of this group compared with methyl. The steric argument is re-
inforced with the observation that monoepoxidation of (18; R' = H, R' =
C0,Me) yields a 35 : 65 ratio of products in favour of oxiran trans to the more
bulky C0,Me group. High stereoselectivity was obtained from the epoxidation of
(19)to a 9 : 1 ratio of epoxides in which (20) predominated.
The presence of base in the oxidizing media dramatically affects the distribution
of epoxide products. In the oxidation of cholesterol acetate with the new reagent
pentafluoroperbenzoic acid, a 65 : 35 mixture of a- : /3-epoxides was obtained
(almost quantitative yield) in CH2CI2at 25 "C; this changed to a quantitative yield
of solely the a-epoxide when Na2C0, was added to the reaction mixture.2sThe
sesquiterpene lactone (21; R'R2 = a bond) gave the cyclized product (22) on
oxidation with 3-CIC6H4C0,H in CH2CI2,but when the same reaction was run
under biphasic conditions, using CH2CI2 and aqueous NaHCO,, it gave the
epoxide (21 ; R'R' = 0)that is the precursor to (22).2h
RZ R3
-Me
A biphasic system has also been used for the generation of the new reagent
0-ethylperoxycarbonic acid (23).27 Ethyl chloroformate in CH2CI2 that is in
contact with an aqueous phase containing 30% H 2 0 2 generates (23) at the
interface. The reaction has the advantages that the conditions may be maintained
by buffering within the pH ranges 6.8-4.5 (Na,HPO,) and 9.5-8.8 (Na,PO,)
and also yields high-purity products. Cyclo-octene oxide is formed in 85% yield
from the cycloalkene.
25 U. M. Dzhemilev, N. S. Vostrikov, A. M. Moiseenkov, a n d G. A. Tolstikov, Izu. Akud. Nuuk SSSR,

Ser. Khim., 1979, 913 (Chew.Abstr., 1979, 91, 108 141).
26
T. Shimizu, Y . Fujimoto, and T . Tatsuno, Chem. Phurm. B i ~ l l .1979,
, 27,934.
*' R. D. Bach, M. W. Klein, R. A. Ryntz, a n d J . W. Holubka, J Org. Chem., 1979, 44, 2569.
Three-Membered Ring Systerits 5
Interest has been shown in the oxides of dicyclopentadiene, as noted earlier,'

with reports of epoxidations using permaleic,2xp e r p h t h a l i ~ ,and
~ ~ peracetic3'
acids. The mechanism of oxidation of trans- stilbene by peroxomonophosphoric
acid (H,PO,) in a number of solvents has been investigated.3' A report on the
epoxidation of a number of methoxy- and hydroxy-substituted cinnamaldehydes
(24; R ' = R2 = R' = H, MeO, or OH) concludes with the suggestion that the
most effective oxidant is 3-ClC6H4C03Hin CHCl,."
Oxidation of Alkenes to Oxirans, using Peroxides. Two reviews in this area have
been published, one dealing with new methods for the catalytic epoxidation of
alkenes using hydrogen peroxide3, and the other with selective oxidation of
alkenes and alkynes with t-butyl h y d r ~ p e r o x i d e . ~ ~
The direct oxidation of alkenes to oxirans by hydrogen peroxide is, of course,
only possible when a catalyst is used. In the past the main choice of catalyst has
been oxides of the metals of Groups 5a, 5b, 6a, or 6b. In 1978, however, Sharpless
put the use of arylseleninic acids as catalysts on a firm practical footing.35Using
the nitrophenylseleninic acids ( 2 5 ; R' = H, R2 = NO2) and ( 2 5 ; R' = R2 =
NOz)? 95% preparative yields of cyclo-octene oxide were obtained from the
alkene in CH2C12with 30% H 2 0 2 .
R ' O iR2e O H OH H 0
A new and more selective catalyst is (26; R = OH); this is a stable oxidizing
agent in its own right, which may be stored for stoicheiometric use or else used
catalytically with H 2 0 2for inexpensive, large-scale epoxidations.36 The reagent,
after oxidizing an alkene, forms hexafluoroacetone hydrate (26; R = H), which
readily regenerates (26; R = OH) under the reaction conditions. The efficiency
of the system is demonstrated by the 90% conversion of cyclohexene into its
epoxide in 15 minutes at 0 "C, while its selectivity in the oxidation of (27) to (28)
(90%) in 12 h at room temperature contrasts sharply with the mixtures of
products obtained using other epoxidation techniques.
Another new group of catalyst systems for direct epoxidations by hydrogen
peroxide is the arsonated polystyrene^.^' Using a triphasic system of CHC13, 30%
HzOz,and the catalyst (in the form of beads), slow but selective epoxidations of
20 V . N . Orekhov and B. M. Rudenko, I Z P . Vysslz. Uchebn. Zaued., Khim. Khitn. Tekhnol., 1Y79, 22,
727 (Chem. Ahstr., 1979, 91, 157 524).
29 M. F. Sorokin, E. L. Gershanova, and Yu. V. Stukalov, Deposited Document, 1978, VINITI 3841
(Chem. Ahsrr., 1980,92, 180 873).
30 C.-T. Huang and H.-T. Han, Hua Hsueh Hsueh Paa, 1979, 37, 2 I (Chem. Abstr., 1979, 91, 56 870).
31 Y. Ogata, K . Tomizawa, and T. Ikeda, J. Org. Chem., 1979,44,2362.
32 R. Olstein and E. F. M. Stephenson, Aust. J. Chem., 1979, 32, 1595.
33
M. Pralus, J . C. Lecoq, and J. P. Schirmann, Fundam. Res. Hornogeneous Card., 1979, 3, 327.
34 K. R. Sharpless and T. R. Verhoeven, Aldrichimica Acta, 1979, 12,63.
35 T. Hori and K. B. Sharpless, J. Org. Cltem., 1978, 43, 1689.
36 R. P. Heggs and B. Ganem, J. A m . Chem. Soc., 1979, 101,2484.
37 S. E. Jacobson, F. Mares, and P. M. Zambri, J. A m . Chem. Soc., 1979, 101, 6946.
R
I
(29)
simple alkenes have been achieved (e.g.90% of cyclo-octene oxide after 2 days at
7 0 "C). The catalyst is removed from the system by straightforward filtration, and
may be recycled.
On treating ethyl orthoformate or acetone dimethyl ketal with 90% H 2 0 2 ,
LY -hydroperoxy-ethers (29) are generated.38 With structural similarities to
peroxo-acids, these compounds are capable of oxygen transfer, and comprise a

new class of epoxidation reagents. The simple experimental procedure of dis-
solving cyclopentene in ethyl orthoformate and adding 90% HzO, results in a
95% yield of the epoxidc.
'The kinetics and mechanism of the epoxidation of allyl chloride by H 2 0 2 in
ethanol, using molybdate catalysts, have been in~estigated.'~''~) The reaction has
been found to be of first order in both allyl chloride and the catalytic species
H,MoO, and of zero order in H 2 0 2 .Supported molybdenum catalysts, prepared
by precipitating MoO(OH), onto silica. were also effective in the epoxidation of
the same substrate with cumyl peroxide."
A group of Russian workers has produced a series of technical reports,
currently to number 11,42that deal with the epoxidation of cyclohexene by
ethylbenzene hydroperoxide, using molbydenum catalysts. The reports explore
the effects of modifications of thc catalyst o n reaction efficiency. The use of
molybdenum catalysts in the oxidation of cyclohexene by cumyl peroxide has
been studied, using i.r. and e.s.r, spectroscopy.'' E.s.r. spectroscopy has also been
used to investigate the decomposition of ethylbenzene hydroperoxide in the
presence of molybdenum n a ~ h t h e n a t e . ' ~
Whitham has reported the stereochemical aspects of the epoxidation of cis- and
trans-5-t-butylcyclohex-2-en- 1-01 when catalysed by [VO(acac),] (Scheme 3).45
Scheme 3
'' J . Rebek, Jr., and R. MeCready, Tetrahedron Le!t., 1979. 1001.
3y I. Ahmad and C. M. Ashraf, Indiun J. Chem., Sect. A , 1979, 17, 302.
4" I. Ahmad and C. M. Ashraf, J. Prakt. Chem., 1979, 321,345.
" J. Sobczak and J . .I. Ziolkowski, React. Kinet. C m l . Lett., 1979, 11, 359.
47
V. N. Sapunov, I. Yu. Litvintsev, T. T. Avakyan, I-. P. Karpenko, V. M . Smagin, B. R. Serebryakov,
and N . N.Lebedev, Deposited Document 1978, VINITI 472 (Cliem. Ahslr., 1979, 91, 157 329).
43
J. Sobczak and J . J . Z,iolkowski, Proc. Cnnf. Coord. Chem. 7th, 1978, 221.
44
L. Sumegi. I. Nemes, I . P. Hajdu, and D. Gal, Oxirl. Cnmnrioi., 1979, 1, 23.
" K. B. Dehnel and G. 14. Witharn. J. Clieni. Snc., Perkiu Trnns. I , 1979, 953.
The trans-alcohol was found to be oxidized 34 times faster than the cis-alcohol,
the enone (32) being the major product from the latter reaction. These results
provide a justification for the proposed intermediate complex (30),since the steric
demands of the transition state that leads to the epoxide (31) would be better
satisfied for the axial alcohol.
Synthesis of Oxirans by Halohydrin Cyclizations and Related Reactions. The
synthesis of precocene 1-epoxide (33; R’R’ = 0) has been achieved via the
bromohydrin cyclization route.46 Several previous attempts at this preparation
had failed, probably owing to the ready cleavage of the oxiran ring; this is to some
extent borne out by the fact that the bromohydrin (33; R’ = OH, R2 = Br) gave
a ring-opened methoxy-alcohol on treatment with anhydrous K2C0, in MeOH.
The required oxiran (33; R’R’ = 0)was isolated in 88% yield from cyclization of
the bromohydrin, using NaH in T H F at room temperature. A convenient one-pot
preparation of a-halogeno-epoxides (35; R = C1 or Br) from (34),avoiding the
need to isolate the intermediate halohydrin, involves the treatment of (34) in
ether sequentially with NaOH in aqueous methanol and then NaBH4.47A yield of
59% for the chloro-oxiran (35; R = C1) was obtained by using this procedure.
Treatment of steroidal bromohydrins with ‘Ag,O’ tends to give ring-contracted

nor-aldehydes when the bromine is equatorial but epoxides or ketones if the
bromine is axial.4R5 P - B r o m o c h o l e s t a n e - 3 ~ , 6-diol(36)
~ has both the 19-methyl
and 6-hydroxyl groups trans, and coplanar with the bromine, and thus in
competition for its displacement. Treatment of this bromchydrin with Ag,O gave
80% of the expected P-epoxide (37) together with 8% of (381, which is the
product of a Westphalen rearrangement. The epoxyphosphorane oxides (39;
R’ = Me, Ph, or OMe; R2, R3 = H or Me) have been prepared from the parent
m
alkene via its chlorohydrin almost q~antitatively.‘~
I\
HO
(37)
(38)
46 R. C. Jennings and P. A. Otteridge, J. Chern. SOC.,Chem. Cornmutt., 1979, 920.
47 J . Gralak and J . Y . Valnot, Org. Prep. Proced. Int., 1979,11, 107.
H . R. Nace and G. A. Crosby, J. Org. Chern., 1979, 44, 3105.
49 F. Cavagna, IJ.-H. Felcht, and E. F. Paulus, A n g e w . Chrm., Inr. Ed. EngI., 1980. 19, 132.
Industrial interest has been shown in the generation of oxirans from vicinal
hydroxy-acetates (by elimination of acetic acid at temperatures of around
400 0C)5".51or from vicinal diols (through conversion into hydroxy-esters in situ
and subsequent cyclization) . 5 2 - s 3
Synthesis of Oxirans via Attack of a Carbanion on the Carbonyl Group of
Aldehydes and Ketones. In the past, this section has been entitled 'Darzens and
Related Reactiyns'; however, with the advent of the now commonly used sulphur
ylides, e.g. Me2S-CH, (Corey's reagent), the new title was necessary. Corey has
shown the sulphur ylide reagents to be of use in the synthesis of relatively unstable
oxirans such as (421,which is air- and acid-sensitive and which is stored at -78 "C
' ~ material has been synthesized froT (40;
in frozen benzene, under a r g ~ n . This
X = OH) in 35% yield, uia the reaction of (40; X = SMe2)
with aldehyde (41). The last stage in+the synthesis of the trichothecatriene
derivative (43) involves the use of Me2S-CH, on its exo-methylene precursor,
the yield being l8'/0.~'
Alternative sulphur reagents that may be used to cause epoxidation are the
N-(p-tolylsu1phonyl)sulphilimines (44; X = H); they are produced (by a phase-
transfer-catalysed process) from the trihydrate of Chloramine-T (the sodium salt
of N-chlorotoluene-p-sulphonamide)with a solution of PhSCH2R in CH,C12.s6
The lithiated materials (44: X = Li, R = H) or (44; X = Li, R = Ph) react with
PhCHO to give quantitative yields of styrene and stilbene respectively.
A Darzens-type condensation has been employed in the synthesis of (46)by the
reaction of 9-chlorofluorene anion (45) with PhCH0.'7 A two-phase system was
used to prepare (E)-(47;R = H, C1, or NO,) almost exclusively, uia a Darzens
reaction of the substituted benzaldehyde with PhCOCH2Br in the presence of a
quaternary ammonium salt as
'O M. B. Sherwin and M. E. Frank, Eur. Pat. Appl. 2561 (Chem. Abstr., 1980, 92, 58 593).
H. Nagai and H. Yokoyama, Jpn. Kokai Tokkyo Koho 79 144 304 (Chem.Absrr., 1980,92,163 830).
52 M. Constantini and M. Michel, Fr. Demande 2 384 764 (Chem. Absrr., 1979, 91, 175 170).
53 H. R. Ansari and R. Clark, Br. P. 1 555 121 (Chem. Absrr., 1980,92, 215 253).
54 E. J . Corey, Y. Arai, and C. Mioskowsky, J. Am. Chem. SOC., 1979, 101, 6748.
" W. K. Anderson and G. E. Lee, J. Org. Chem., 1980,45, 531.
''
57
C. R. Johnson, K . Mori, and A . Nakanishi, J. Org. Chem., 1979, 44, 2065.
M. Jawdosiuk, A. Jonczyk, A. Kwast, M . Makosza, I. Kmiotek-Skarzynska, and K.
Wojciechowski, Pol. J. Chem., 1979, 53, 191 (Chem. Ahstr., 1979, 91, 30 181).
R . Annunziata. Synth. Commun.. 1979. 9, 171.
Two methods have been suggested for the synthesis of vinyl-oxirans, both
involving the attack of allylic carbanions on aldehydes or ketones. Cyclization of
R ' R 2 C 0 with (48) gives tri- or tetra-substituted epoxides (49; R' = R' =
various alkyl groups) (31--87'/0).'~ Treatment of 2-allyloxy-benzimidazoles with
BuLi, followed by Cd12, generates the metallated allylic ethers, which give
adducts with aldehydes that can be converted into the trans-disubstituted vinyl-
oxirans, e.g. (50; R = Me or H) (82-95%) by NaH."'
CI RZ Me
)=CHCH,Li + RIRZCO -+ R i v ~ H = ~ ~ ,
0
Me (48) (49) (50)
Synthesis of Chiral Oxirans. This section has been restricted to syntheses in which
an enantiomeric excess (e.e.) of one isomer is obtained directly (i.e. it excludes
syntheses that rely on the resolution of racemic epoxides).
A method for the production of chiral oxirans from simple unfunctionalized
alkenes employs the molybdenum peroxo-complex ( 5 l), which has a pentagonal-
bipyramidal structure." The oxidations of propene, but-1 -ene, and but-2-ene
yield e.e.'s of around 30% [all of ( R ) configuration] in PhNO, at 20 "C.
The dioxolan (R)- ( 5 2 ; X = tosyloxy), obtained from di-isopropylidene-
mannitol, undergoes substitution reactions with CuI plus XLi (X = Me or Bu)
to yield ( S ) - ( S 2 ; X = Me) and ( S ) - ( 5 2 ; X = B u ) . ~
Sequential
~ treatment of
this dioxolan with HBr and HOAc (to form the bromoacetate) and then
Me(CH2)40K and Me(CH,),OH gave samples of the 6)-alkyl-oxirans (53;
R' = H, R2 = CH,Me) and (53; R' = H, R' = CH2Bu)with high optical purity.
Racemic halohydrins, on treatment with an insufficient amount of (-)-quinine,
underwent dehydrobromination to give the corresponding epoxide with an e.e. of
rfCHzX Ph
O X 0
R'
kf
R2 'CH-CH
I I
/Ph
Me Me 0 OH Br
'' B. Mauze, J. Organomet. Chem., 1 9 7 9 , 1 7 0 , 265.

6o M. Yamaguchi and T. Mukaiyama, Chem. Lett., 1979, 1279.
61 H. B. Kagan, H . Mimoun, C. Mark, and V. Schurig, Angew. Chem., Znf. Ed. Engl., 1979, 18, 485.
62 U. Schmidt, J . Talbiersky, F. Bartkowiak, and J . Wild,,Angew. Chem., Znt. Ed. Engl., 1 9 8 0 , 1 9 , 198.
12--35%." A distinct advantage of this technique is that the easily recovered

unreacted halohydrin mixture is enriched with the less reactive isomer; this, on
elimination of HRr, gives an e.e. of the other epoxide epimer. Thus racemic
[ ( l S , 2 R ) -and (lR,2S)-]erythro-(S4)reacts with (-)-quinine in benzene to give
trans-(53; R' = R2 = Ph) with (R,R) prevailing configuration, and the bromo-
hydrin that is recovered yields rrans-(53; R' = R2 = Ph) with ( S , S ) prevailing
configuration on treatment with excess Et,N in benzene. An optically active
[Co"(salenj]-type catalyst has been used to generate chiral methyloxiran by
elimination of HCl from racemic propene c h l ~ r o h y d r i n sThe. ~ ~ highest optical
purity obtained was 35% of (S)-methyloxiran from 2-chloropropan- 1-01 and
K2C03,for which the (R)-chlorohydrin isomer was the more reactive. In the case
of racemic 1-chloropropan-2-01, however, the ( S ) -chlorohydrin isomer was more
reactive, giving rise to (R)-methyloxiran.
The synthesis of optically active cyclohex-2-enone oxide (55) from cyclohex-2-
enone has been reported.65 The epoxidizing medium contained a chiral catalyst
(quininiurn benzyl chloride) with Bu'OOH and a small amount of solid NaOH in
toluene. This heterogeneous mixture avoided the use of the strongly alkaline
aqueous phase which may have been responsible for the failure of earlier attempts
at direct, chiral synthesis of ( 5 5 ) . Chemical yields of 60'10 were obtained, with an
*
e.e. of 20 3%.
The displacement of the leaving group X from the compounds ( S ) - ( 5 6 ;
X = CI), ( S ) - ( 5 6 ;X = OMS),and (S)-(56;X = OTf) by the phenoxide nucleo-
philes 4-RC6H40H (R = H, CN, or OMe) might be expected to yield ( S ) - ( 5 7 ;
Nu = 4-RC6H40)by normal nucleophilic displacement.h6An alternative path-
way via nucleophilic ring-opening to (58) yields the enantiomeric epoxide
( R ) - ( 5 7 (Scheme
) 4). By suitable choices of reaction conditions, pure ( R ) -or
( S ) - ( 5 6 )may give aryloxymethyl-oxirans (57) with from 5% to 98% retention of
configuration.
Scheme 4
Oxiran (59) and its enantiomer are synthetically useful intermediates that may
be prepared from the readily available enantiomeric forms of tartaric
Similarly, (60) and its enantiomer have been synthesized. The absolute
configuration of (-)-trans- (61) has been chemically established as (2R,3S).68
What could be a most useful technique for the estimation of enantio-
meric mixtures of oxirans is complexation gas c h r ~ m a t o g r a p h y .Separations
~~'~~
63 V. Calo, L. Lopez, V. Fiandanese, F. Naso, and L. Ronzini, Tetrahedron Lett., 1978,4963.
64 T. Takeichi, M. Ishimori, and T. Tsuruta, Bull. Chem. Soc. Jpn., 1979, 52, 2614.
65 H . Wynberg and B. Marsman, J. Org. Chem., 1980, 45, 153.
66 D. E. McClure, B. H. Arison, and J. J. Baldwin, J. A m . Chem. Soc., 1979, 101, 3666.
67 E. Hungerbuehler, D. Seebac , and D. Wasmuth, Angew. Chem., Int. Ed. Engl., 1979,16, 958.
B. Marsman and H. Wynberg, J. Org. Chem., 1979, 44, 2312.
69 V. Schurig, B. Koppenhoefer, and W. Buerkle, Angew. Chem., Int. Ed. Engl., 1978, 17,937.
70 V. Schurig, B. Koppenhoefer, and W. Buerkle. J. Org. Chem., 1980, 45, 538.
have been achieved for the propene and butene oxides, using the optically
active complexing agent nickel(II)-bis[(R )-heptafluorobutanylcamphorate] in
squalene.
Synthesis and Reactivities of Aromatic Oxides. Much of the work in this area is
generated from an interest in the carcinogenicity of many of the fused-ring
aromatic oxides. Some syntheses of arene oxides” and the chemistry of diol
epoxides7*have been reviewed.
In a study of the fungal biogenesis of gliotoxin, the ring-opening of an arene
oxide by internal nucleophilic attack by the NH2 of a P-arninoethyl group was
. ~ ~benzene oxide (63) was synthesized from lactone (62), but the
i n ~ e s t i g a t e dThe
amino-group did not function as an internal nucleophile. This lack of reactivity
H
(62) CHlCHzNH2
Rd--
was attributed to the low ‘nucleophilic susceptibility’ of the arene oxide.
R\
(64) R = H
/
(63) ( 6 5 ) R-R = (CH)4
The first examples of the preparation of optically pure arene oxides have been
reported with the syntheses of (64) and its benzo-derivative (65).74Starting from
trans-2-bromo-1 -hydroxy-1,2,3,4-tetrahydro-naphthalene and -anthracene, the
diastereoisomeric menthyloxyacetal derivatives were prepared and resolved.
This was followed by sequential deacylation, acetylation, bromination, and ring
closure/dehydrobromination to yield (64) ([a], +149”) and (65) ([a],, +214”).
The reactivities of bay-region and non-bay-region tetrahydro-epoxides of
phenanthrene, i.e. (66) and (67) respectively, towards a number of oxiran-
opening reactions have been ~ o m p a r e d . ~Despite
’ the proven greater carcino-
genicity of bay-region isomers of polycyclic epoxides, this study has shown no
significant difference between the reactivity of isomers in the systems studied.
71 Anon, Nachr. Chem., Tech. Lab., 1979, 27, 94 (Chem. Abstr., 1979, 91,20 350).
72 R. G. Harvey and P. P. Fu, in ‘Polycyclic Hydrocarbons and Cancer’, ed. H. V. Gelboin and P. 0. P.
Ts’o, Academic Press, New York, 1978, Vol. 1, p. 133.
” W. H. Rastetter and L. J. Nummy, Tetrahedron Lett., 1979, 2217.
74 M. S. Naseem, D. R. Boyd, and J. G. Hamilton, J. Chem. SOC.,Perkin Trans. I, 1979, 2437.
’’ D. Z. Rogers and T. C. Bruice, J. Am. Chem. Soc., 1979, 101,4713.

The K-region phenanthrene oxide (68)undergoes photochemical ring-enlarge-

ment to (69) via the singlet excited A similar photochemical re-
arrangement for the K-region 3,4-epoxy-3,4-dihydropyrenewas also reported.
The isomeric diol epoxides (70; R'R' = 0) and (71; R ' R 2 = 0) have been
synthesized from chrysene by epoxidation of the corresponding 1,2- and 3,4-
trans-dihydro-diols (70; R'R' = a bond) and (71; R'R2 = a bond).77 The
syntheses of the chrysene dihydro-diols were accomplished in only seven steps
from chrysene. Epoxidation of (70; R'R2 = a bond) with 3-ClC6H,C0,H affords
the anti-diol epoxide (70; R'R' = 0) stereospecifically, whereas similar reaction
of (71; R'R' = a bond) gives the corresponding anti- and syn-diol epoxides in a
ratio of 5 : 3. The synthesis and isolation of the first examples of conformationally
rigid diastereoisomeric pairs of diol epoxides from trans- dihydro-diols has been
in the benzo[e]pyrene and triphenylene ~ysterns.~' Epoxidation of the dihydro-
diol (72; R'R' = a bond) with 3-CIC,H4C0,H gave a 1 : 1 mixture of the two
possible diol epoxides (72;R'R2 = 0)(with the oxiran ring cis or trans to
benzylic OH) in which the O H groups are held in quasi-axial conformations. A
similar mixture was obtained on oxidation of (73; R'R' = a bond). The highly
mutagenic diol epoxides of the dibenzo-[a,i]- and -[a,h]-pyrenes (74) and (75)
have also been prepared from their respective dihydro-diols."
(70) (71) (72) R'R? = CH=CH

( 7 3 ) R' = H
(74) (75)
Miscellaneous Syntheses of Oxirans. Vitamin K , and a model compound, 2,3-

dimethyl-l,4-naphthoquinone,have been oxidized at room temperature by KO,
in the presence of 18-crown-6 in benzene under a stream of 0, to yield (76;
R = phytyl) and (76; R = Me) in 16% and 7% yields, respectively.8'' The
76 M. Itoh, K. Murata, K. Tokumura, K. Shudo, and N. Miyata, Tetrahedron, 1979, 35, 1059.
77 P. P. Fu and R. G. Harvey, J. Org. Chem., 1979,44, 3778.
78 H. Yagi, D. R. Thakker, R. E. Lehr, and D. M. Jerina, J. Org. Chern., 1979,44, 3439.
79 R. E. Lehr, S. Kumar, P. T. Cohenour, and D. M. Jerina, Tetrahedron Lett., 1979, 3819.
I. Saito, T. Otsuki, and T. Matsuura, Tetrahedron Lett., 1979, 1693.
mechanism of the reaction is thought to involve the superoxide ion (023.A

similar epoxidizing system, using MeCN as solvent, oxidized chromanol (77) to
diepoxide (78) in 23% yield.81
The first isolable dichloro-oxirans have been produced by the cycloaddition of

dichlorocarbene to the carbonyl group of 7,7-dimethylbicyclo[3.2.0]hept-2-
en-6-one under phase-transfer conditions. Both (79) and (80)were isolated from
the product mixture."
Me Me
(79) (80)
The first successful trapping and isolation of epoxy-diols as products from the
oxidation of a steroidal diene with K M n 0 4 was achieved when cholesta-5,7-diene
3P-acetate (81)was oxidized predominantly to (82).8' The reaction appears to be
a generally useful one of steroidal 5,7-dienes.
A new method for the synthesis of perfluorinated epoxy-alkanes involves the

treatment of RCF=CFCF3 with M(OX), (M = Na, K, Ba, or Ca; X = C1 or Br;
n = 1 or 2 ) to give the compounds (83; R = CF3, C2F5or C3H7)(69-94'/0).'~
Thallium(rI1)salts have been used for epoxidation of alkenes.8s Oct-1 -ene with
T1Cl3 in THF-H20 gave only octan-2-one (60% selectivity) whereas T1(O2CEt),
in THF-H,O-EtC0,H showed selectivities to formation of oxiran and of ketone
of 80 and 13 ' / o , respectively.
81
M. Matsuo, S. Matsumoto, Y. Iitaka, A. Hanaki, and T. Osawa, J. Chem. SOC., Chem. Commun.,
1979, 105.
82
H. Greuter, T. Winkler, and D. Bellus, Helu. Chim. Acta, 1979, 62, 1275.
83
M. Anastasia, A. Fiecchi, and A. Scala, Tetrahedron Lett., 1979, 3 3 2 3 .
84
I. P. Kolenko, T. I . Filyakova, A . Ya. Sapevalov, and E. P. Lurle, Izu. Akad. Nauk SSSR, Ser. Khim.,
1979,2509 (Chem. Abstr., 1980, 92, 94 148).
85
J. Dahlrnann and B. Klose, 2. Chem., 1 9 7 9 , 1 9 , 3 7 1 .
Spectra and Theoretical Chemistry of 0xirans.-Electrophilic additions to a

series of norcarene derivatives to yield the oxirans (84; R' = H, R2 = Me), (84;
R' = Me, R2 = H), and (85) have been described.8h Proton n.m.r. spectra and
X-ray structures for these oxirans are given, and their conformations have been
established. The chemical shifts and coupling constants for the ' H and I3C n.m.r.
spectra of a series of cis- and trans-epoxystilbenes have been r e p ~ r t e d . ' ~
/-\An R2 R'
The 13C n.m.r. spectra of the monoepoxide and the diepoxide (86) of cyclo-
octa-1,5-diene were studied at -10 to -180 0C.88The former was found to exist
in a twist-boat conformation, rapidly pseudorotating even at - 180 OC, whereas
(86) exists in the chair (major) and twist-boat (minor) conformations. The I3C
n.m.r. spectra of five glycidic esters (87; R',R2,R3 = H or Me) were compared
with those of the alkenes from which they were formed." The line separations
from geminal and vicinal C-H couplings in the esters are within narrow ranges,
and allow the assignment of carbon resonances and configurations of epoxide
rings.
Natural-abundance 1 7 0 n.m.r. spectra have been recorded for 21 oxirans,
including those derived from the norbornene and benzonorbornene
The "0 chemical shifts cover a range of 100 p.p.m. and have been interpreted in
terms of the paramagnetic p- and diamagnetic y-effects.
The conformations of oxirans may be determined by studying dipole moments.
For a number of substituted epoxy-styrenes, conjugation between the aromatic
and oxiran rings is unimportant and, in the absence of steric or electrostatic
~ ' one conformer is observed for (88;
hindrance, internal rotation is p o ~ s i b l e .Only
R = Me) and for (88; R = Ph); the carbonyl group is rotated some 40" out of the
plane of the oxiran ring, with the oxygen atoms facing away from each
Two conformations of (89) have been revealed by microwave s p e c t r o s ~ o p y . ~ ~
One form has the CI cis to the 0 in the ring and the second (gauche-2) has the C1
trans to the oxygen atom.
The ionization and excitation energies of an isoelectronic series of three-
membered rings, including oxiran, have been calculated by the semi-empirical
H A M / 3 method and compared with experimental values.94
86
L. A . Paquette, W. E. Fristad, C. A. Schurnan, M. A . Beno, and G . G. Christoph, J. A m . Chem. SOC.,
1979,101,4645.
M. Irnuta and H. Ziffer, J. Org. Chem., 1979, 44, 2505.
88
F. A . L. Anet, N . R. Easton Jr., and I. Yavari, Org. Magn. Reson., 1979, 12, 299.
89
U. Sequin, Tetrahedron Lett., 1979, 1833.
90
H. Iwamura, T. Sugawara, Y. Kawada, K. Tori, R. Muneyuki, and R. Noyori, Tetrahedron Lett., 1979,
3449.
91
S . Sorriso, Z. Naturforsch., Teil. B., 1979, 34, 1298.
92 B. A . Arbuzov, A . N. Vereshchagin, and A . I. Donskova, Izv. A k a d . Nauk SSSR, Ser. Khim., 1979,
1257 (Chem. Abstr., 1979,91, 123 306).
93 M. A. Mohammadai and W. V. F. Brooks, J. Mol. Spectrosc., 1979, 7 8 , 89.
94 C. Fridh, J. Chern. SOC.,Faraday Trans. 2, 1979, 7 5 , 993.
(88) (89) (90)

The reaction of oxiran with H F to yield C H 2 F C H 2 0 Hwas chosen as the model
for the ring-opening of epoxides that is caused by halogen acids, and theoretical
ab initio calculations for the reaction were p e r f ~ r m e d . ' ~For the gas-phase
reaction, the preferred mechanism leads to retention of configuration at the
carbon atoms of the ring. An alternative pathway via preliminary formation of
the conjugate acid of the oxiran was found to fit a borderline A2 mechanism.
Calculations show that hydrogen-bonding does not possess an intrinsic capacity
for weakening C - 0 bonds of ~ x i r a n s . 'This
~ result therefore argues against the
effectiveness of hydrogen-bonding in catalysing ring cleavage.
A detailed study of eleven possible isomers of C2H40" has been carried out
with the aid of ab initio M.O. Results indicate that (90) is relatively
stable, with a calculated energy that is in reasonable agreement with
thermochemical data.
Reactions of Oxirans with E1ectrophiles.-Ring-opening Reactions. Oxiran
undergoes a Friedel-Crafts reaction with toluene in the presence of AlCI, at
-5 "C to give a mixture of 2-tolylethanols (75%).'* On warming to 3 5 - 4 0 "C,
however, further reactions occur, giving 1,2-ditolylethanes. A Friedel-Crafts
reaction of t-butyloxiran with anisole gave products derived from the re-
arrangement of the oxiran to 2,3-dimethyl- l-hydroxybutan-2-yl carbo-cation in
the presence of the Lewis acid catalyst.99
The novel fragmentation reaction of (91) [ ( 3 R ) -and (3s)-isomers] to give
acetone and (94; R = H ) (go0/,) occurs in 1 minute at room temperature in the
presence of BF3*Et20,'00A similar reaction of (92) gave (94; R = 'H); both
reactions are believed to proceed via the intermediate oxetan (93), as shown in
Scheme 5.
Me
Me (91)
(92) Scheme 5
9s G. Alagona, E. Scrocco, and J. Tomasi, Theor. Chim. Acra, 1979, 51, 11.
96
P. Politzer and V. M. Estes, Jerusalem Symp. Quantum Chem. Biochem., 1979, 12, (Catal.
Chem. Biochem. Theory Exp.) 305 (Chem. Ahstr. 1980,92, 163 440).
'' W. J. Bouma, J. K. MacLeod, and L. Radom, J. A m . Chem. SOC.,1979,101, 5540.
98 J. Joers and H. Urbel, Zh. Org. Khim., 1979, 15, 790 (Chem. Abstr., 1979, 91, 74 268).
q9 M. Inoue, M. Harada, N. Urnaki, and K. Ichikawa, Bull. Chem. SOC. Jpn., 1979, 52, 1873.
loo I. Morelli, S. Catalano, V. Scartoni, M. Ferretti, and A. Marsili, J. Chem. SOC..Perkin Trans. I , 1979,
1665.
Two papers describe the effects of BF,.Et,O-catalysed rearrangement of

epoxylanostanone (95). Using A c 2 0 as solvent, a mixture of products was formed
from which cucurbitane (96) was isolated (51-58°/~).*(" In MeNO,, however, no
migration of a methyl group occurred, and the diketone (97) (80%) was
forrned.'O2 Carbon-13 n.m.r. spectral data for a number of compounds related to
(95) are given in the latter paper.
For the 9a,lla-epoxypregn-4-en-3-one [98; R' = OH, R2 =
CH(OAc)CH,OAc], treatment with BF,.Et20 leads to the steroid (99), in which
ring c is aromatic.'"'
Cyclization Reactions of Oxiruns. By suitable choice of substituent and reaction

conditions, the epoxycyclohexenone (100) may be converted into bi- and tri-
carbocyclic ring Thus (101), (102), and (103) were synthesized uiu
(100; R = CH2CH2CH=CH2), (100;R = CH2CH2CH=CMe2)and (100; R =
3-MeOC6H4CH2CH2), respectively.
w
Me
0 OH
The (2)-styryloxirans (104; R' = R2 = C02Me, R3 = R4 = H),(104; R' =

C02Me, R2 = R4 = H, R' = Ph), and [104; R ' = Ph, R2R4 = (CH,),, R' = HI
underwent cyclization involving phenyl participation, o n thermolysis at 370 "C, to
give benzoxepins (105).'(''
lo' Z. Paryzek, J. Chem. SOC.,Perkin Trans. 1, 1979, 1222.
lo2 G. V. Baddeley, J. H. Samaan, J . J. H. Simes, a n d H. A. T u , J. Chem. SOC.,Perkin Trans. 1, 1979, 7 .
103
H. T. A. Cheung, R. G. McQueen, A. Vadasz, and T. R. Watson, J . Chem. Soc., Perkin Trans. I,
1979, 1048.
Io4 J . K. Sutherland, I n t . Congr. Ser. - Excerpta Mrd., 1979, 457 (Stereosel. Synth. Nat. Prod.) 142.
lo' W. Eberbach, B. Burchardt, and U. Trostmann, Tetrahedron Lett., 1979, 4049.
A biomimetic synthesis of (*)-pallescensin A (107; R = H) has been achieved

through the concerted BF3.Et20-inducedcyclization of epoxide (106) to yield
crystalline (107; R = OH) (25%), followed by subsequent deoxygenation.'"6 The
cyclization of the parent diene with BF3-Et20gave (107; R = H) directly (84%)
as an almost pure oil.
( 104) (10 5 ) ( 106) ( 107)

The reaction of the ene-allenes (108; R = H or Me) with monoperphthalic acid
in CH2Cl, plus E t 2 0 gave (109) via an intermediate epoxide, which cyclized
under the reaction conditions employed.'"' Compounds such as (109) are key
intermediates in the synthesis of macrocyclic ketones such as exaltone and
muscone.
CHMe,
( 109) (110)
Treatment of epoxygermacrene D (110) with 80% aqueous AcOH at 0 "C for 1
hour gave a mixture of products from which were isolated selinane-type
compounds (112; R = H or Ac) (21'/0) and oppositol-type compounds (113;
R' = OAc or OH, R2 = H) and (113; R' = H, R2 = OAc or OH) (29°/~),10R The
oppositol products are thought to arise via ring contraction of the intermediate
carbo-cation (111). Oppositol compounds were also produced when (110)
reacted with AICI, in E t 2 0 . The germacrone 4,5-epoxide (114) underwent
AIC1,-catalysed cyclization to the epimeric caulolactones A and B (115; R = a -
H) and (115; R = P-H) respectively.""
CHZ
CHMe,
HzC OR
CHMe, @.
H ZC
(113)
'CHR 'CMe, R2
'06 D. Nasipura and G . Das, J. Chem. Soc., Perkin Trans. 1, 1979, 2776.
'07 M. Bertrand, J . P. Dulcere, G. Gil, and M. L. Roumestant, Tetrahedron Lett., 1979, 1845.
'08 M. Niwa. M. Ieuchi. and S. Yamamura. Tetrahedron Lett., 1978,4043.
A new synthesis of the hydroazulenone (119) has been reported, from the
bicyclic dione (116) (Scheme 6)."() tnitial conversion of (116) into the spiro-
oxiran (117) by Corey's reagent (Me2S-CH2) is followed by BF3.Et20-catalysed
rearrangement via the carbo-cation (118) to the azulene derivative (1 19).
Nucleophilic Ring-opening Reactions of 0xirans.-Reactions with Oxygen and

Nitrogen Nucleophiles. A series of papers have appeared that deal with the
reactions of lower aliphatic alcohols ( R 2 0 H )with (120; R' = Me) to yield (121;
R' = Me) and (122)."' An S,2 mechanism has been confirmed by kinetic
studies, which showed that the ratio of products (121; R' = Me) to (122)
decreases as the temperature of the reaction is raised but increases with complex-
ity of alkyl group R'. A mathematical model for the reaction was developed.
R' 0 HO R20
R' Me
The kinetics of the ring-opening reaction of (120; R' = H) with variously

substituted phenols in the presence of PhCH2NEt, + CI- to give (121 ; R' = Me,
R2 = substituted phenyl) have been reported.Il2 A Hammett p-u plot revealed
two mechanisms for the reaction: ( a ) for electron-donating substituents, the
rate-determining step is the reaction of phenoxide ion with the carbon atom of the
oxiran and ( b ) for electron-withdrawing substituents, proton transfer from the
phenol to the oxygen atom of oxiran is rate-determining. A study of the rates of
opening of ethene oxide by various monosubstituted phenols to 2-
phenoxyethanols, in PhN02, produced a p value of - 0.3.'13
The effect of temperature on the stereochemistry of the acid-catalysed
ethanolysis of trans-stilbene oxide has revealed two reaction mechanisms,
operating c~ncurrently.''~ The oxiran ring may open either ( a ) by nucleophilic
110
P. Geetha, K. Narasimhan, and S. Swaminathan, Tetrahedron Lett., 1979, 565.
111
J . Svoboda and V. Macho, Chem. Zvesti, 1979,33,252,259,270 (Chem. Abstr., 1979,91,210 843,
156 943, 156 944).
112
Yu. 0.Golubok, K . A. V'yunov, 0.A. Podzolkova, A. I. Ginak, and E. G . Sochilin, Zh. Org. Khim.,
1979, 15. 2106 (Chem. Absrr., 1980. 92, 75 458).
I13
P.Sallay, J. Morgos, L. Farklas, B. Bartha, and I. Rusznak, Period. Polytech., Chem. Eng., 1979,23,
29 (Chem. Abstr., 1979, 91, 73 885).
114
M. Inoue, Y. Taguchi, T. Sugita, and K . Ichikawa, Bull. Chem. SOC.Jpn., 1979, 52, 1743.
attack on the carbon atom of the conjugate acid, leading to inversion, o r ( b )via an
intermediate that is of carbo-cation nature, giving retention. The latter
mechanism becomes more important as the reaction temperature is raised.
Phenols (ArOH) react stereospecifically with threo- (123 ; R' = H, R2 = Me)
and erythro-(123; R' = Me, R2 = H) under basic conditions to yield cis-(124;
R' = H, R2 = Me) and trans-(124; R' = Me, R2 = H) re~pectively."~The
proposed mechanism parallels that shown in Scheme 4, in which the oxiran is
opened to an alkoxide by nucleophilic attack and then re-cyclizes by elimination
of Br- .66 The (phenoxymethy1)oxirans thus formed may be converted into threo-
and erythro-1-aryloxy-3-(alkylamino)butan-2-ols by heating under reflux with
aqueous solutions of alkyl-amines.
R1*
Br
-v
H
' 6 H 2 0 A r
(123)
R
R2
( 124)
QH
(125)
& (126)
With internal nucleophilic ring-opening, cyclization may occur; thus the epox-
idation of (125)by 3-CIC,H4C0,H produces an epoxide which cyclizes and, after
oxidation in situ, gives (126j.l'' Reduction of (127; R' = H or Me, R2 = H or
OMe, R3 = H or OMe) with LiAlH4 and AIC13 (1 : 7) leads, uia cyclization, to
(128) in 15-20% yields."'
Treatment of (129) with phenylhydrazine in ethanol at reflux gives (130) via

initial formation of the phenylhydrazone and subsequent cy~lization."~The
condensation of chloral hydrate, CC13CH(OH)2, with ethene oxide in the
presence of a phase-transfer catalyst (dialkylmorpholinium bromide) gave (131)
(90Y0)."~
H. Tucker, J. Org. Chem., 1979.44, 2943.

G . B. Bennett, U.S. P. 4 170599 (Chern. Abstr., 1980, 9 2 , 4 1 764).
'I7 D. D. Berge and M. M. Bokadia, Indian J. Chem., Sect. B, 1979, 18, 77.
T. I. Akimova, M. N . Tilichenko, and T. V. Khaidukova, Zh. Org. Khim., 1979, 15, 516 (Chem.
Abstr., 1979, 91, 39 413).
'I9 M. M. Movsumzade, A, L. Shabanov, and G. Kh. Mamedov, Izv. Vyssh. Uchebn. Zaved., Khim.
Khirn. Tekhnol., 1979, 22, 758 (Chern. Abstr., 1979,91, 157 711).
Nz~leophilicRing-opening Reactions with Carbanions. The anion of methyl

3-oxobutanoate, generated by adding NaOH in MeOH, reacts with ethene oxide
to yield a -acetyl-y-butanolactone ( 132).12'
Trimethylsilylacetonitrile (133) is prepared in high yield (81%) from the
reaction of BrCH2CN with Me,SiCI and zinc in benzene--THF.l2l On treatment
with LiAIH, in Et,O, the anion of (133) is formed; this readily opens propene and
but-1-ene oxides to (134; R = Me) and (134; R = Et), respectively.
\ CH2CN RPC
OSiMe,
A H o d C H , R A.
(135) (136) R = (CH2)20H (138)
(137) R = H
The 2-methyleneallyl dianion (135) reacts smoothly with ethene oxide to give
(136) (80%) and (137) (5'/0).l~~The latter can be prepared in 72% yield by the
reaction of oxiran with the monoanion ( 1 38).
The reaction of the epoxide (139) in T H F with BuLi at -78 "C leads to the
macrocyclic terpenoid ( 140).123
The butadienyl Grignard reagent (141) reacts with oxirans to yield normal
ring-opened products (142) and the rearranged allenic products ( 1 43) (Scheme
7).12, Steric factors greatly influence the product distribution, from 100% of (142;
R' = H, R2 = Me) to product ratios for (142) to (143) of 91 : 9 [R'R2 = (CH,),]
and 6 0 . 4 0 (R' = R2 = Me). The presence of A1CI3 also caused a remarkable
R' R2 HZc=C-7
v 0
R'(-Rz
(143) O H
Scheme 7
I2O R . Costescu, M. Iulian, A . Maza, I . P. Ambrus, M. Ionescu, V. Tamas, H. Aftalion, P. Dimofte, M.
Lidia, and R. Sirnionovici, Rom. P. 63 127 (Chem. Abstr., 1980, 92, 2 2 0 7 4 ) .
12' I. Matsuda, S. Murata, and Y. Ishii, J. Chem. SOC.,Perkin Trans. I, 1979, 26.
'22 R. B. Bates, W. A. Beavers, B. Gordon, and N. S . Mills, J. O r g . Chem., 1979, 44, 3800.
12' M. Y. Kodama, K . Shimada, S. Yokoo, a n d S . Ito, Int. Congr. Essent. Oils, ( P a p . ) ,7th 1977, 7 , 306.
'24 S. Nunomoto and Y. Yarnashita, J. O r g . Chem., 1979, 44, 4788.
change in the product ratio, i.e. to 60 : 40 for (142; R' = H, R2 = Me) and 48 : 52
for [142; R'R2 = (CHJ4].
The catalysis of the reaction of Grignard reagents with cyclohexene oxide by
Cu21, to yield truns-alcohols under mild conditions has been quantified.'25 In
THF, at 0"C, for 2 hours, the yield of alcohols is increased from 3 to 82%
(PhMgBr) and from 6 to 58% (Bu"MgRr). Mixed cyanocuprates RCuCN- Lit
have been found to cause regioselective 1,4-addition of the alkyl group (R) to the
monoepoxides of cyclohexa- and cyclohepta-diene, i.e. (144; n = 1 and 2), to
yield the corresponding allylic alcohols (145; n = 1) and (145; n = 2).Iz6
OH
(144j (145)
Reduction and Elimination Reactions of 0xirans.-New and simple methods for

the deoxygenation of epoxides to alkenes have been r e ~ 0 r t e d . Treatment
I~~ of
epoxides [146; R ' = octyl, H, decyl, or Me; R2 = H, octyl, or Me; R3 = octyl,
tridecyl, or MeO(CH&; or R2R3 = (CH2),",R4 = H or Me] with P214,PI3, or
MeSiI affords a conversion into alkenes that is 100% stereoselective. P214 has
also been used in the deoxygenation of (146; R' = heptyl, R2 = R3 = R4 = H)
and (146; R' = R' = Ph, R3 = R4 = H), in 92% and 70% yields, to their
respective alkenes. The stereochemistry of each epoxide appears to be retained
in the alkene products.
The zerovalent titanium bis(benzene) complex (147) has been found to deoxy-
genate propene oxide efficiently in THF, at 8O"C, to propene (100%) in 2
hours.
truns-Stilbene oxide (148) is reduced to 1,2-diphenylethane (149) (100%) with
Et,SiH and BF3 in CH2C12 at 20 "C with a reaction half-life of 24 h.I3' This
apparently simple reduction has been examined by both 'H n.m.r. spectrometry
and chemical methods and been shown to involve multiple phenyl migrations
(Scheme 8). The reduction of cyclohexene oxide to cyclohexane was very slow
under these conditions.
12s
C. Huynh, F. Derguini-Boumechal, and G. Linstrumelle, Tetrahedron Leu., 1979, 1 503.
'26 J. P. Marino and D. M. Floyd, Tetrahedron Lett., 1979, 675.
12' J. N. Denis, R. Magnane, M. Van Eenoo, and A. Krief, Nouu. J . Chim., 1979, 3, 705.
12' H. Suzuki, T. Fuchita, A. Iwasa, and T. Mishina, Synthesi.7, 1978, 905.
I29
H. Ledon, I. Tkatchenko, and D. Young, Tetrahedron Lett., 1979, 173.
I3O J. L. Fry and T. J . Mraz, Tetrahedron Letf., 1979, 849.
Ph
___* Ph&(H I1 P h H H
p h 0, 4 h M Ph p . H __*
fast fast H O-BF2 SIOW H H
PhCH ,CH,Ph
Reagents: i, BF,; ii, Et,SiH
(149)
Scheme 8
Brown has reported the exclusive Markovnikov reductions of epoxides to

alcohols with lithium triethylborohydride (LiEt,BH) in THF.l3' The reducing
agent seems more powerful than LiAIH4 and is claimed to be the most powerful
nucleophile available to organic chemists. The only reported minor exception to
the total exclusivity of Markovnikov reduction is the opening of styrene oxide
(150) to (151) (97%) and (152) (3%).In contrast to this, the reagent NaBH3CN in
THF containing BF3 regioselectively opens epoxides in an anti-Markovnikov
sense, reversing, for example, the proportions of alcohols obtained from (150) to
3% of (151) and 97% of (152).13*
Ph Ph CH, Ph
I7 YOH L C H ,
I
0 OH
(150) (151) (152)
The reduction of py-epoxy-sulphones has been used as a new synthesis of

a -methylene-~arbinols.'~~ The epoxy-sulphone (153), prepared from 1-cyclo-
hexenylmethanol, was reductively eliminated by Na(Hg) in THF-MeOH to
methylenecyclohexanol ( 154). The same reduction/elimination procedure
comprises part of that for a general synthetic sequence of allylic alcohols (156;
R',R2,R3 = H or Me, R4 = hexyl), uia fly-epoxy-sulphones (1551, in 60-90%
l ~ ~ group R4 may be introduced by alkylation of (155; R4 = H).
~ i e 1 d s .Any
Epoxy-methylsulphonates (158) have been used as intermediates in a

stereoselective 1,3-transportation reaction of the allylic alcohols geraniol (157;
R = H) and farnesol (157; R = Me2C=CHCH2) to linalool and nerolidol,
respectively (Scheme 9).13'
A preliminary report on asymmetric induction in the formation of cyclohex-2-
enol from cyclohexene oxide has appeared.'36 Using chiral lith um amide bases,
13' H . C . Brown, S. C. Kim, and S. Krishnamurthy, J. Org. Chem., 1980,45, 1 .
"* R . 0. Hutchins, Ventron Alembic, 1977, 2 (Chem. Abstr.. 1979, 91, 4688).
133 P. J. Kocienski and J . Tideswell, S y n f h . Cornmiin., 1979, 9, 411.
P. J . Kocienski, Tetrahedron Lett.. 1979. 441.
135
A. Yasuda, H . Yamamoto, and H . Nozaki, Bull. C h e m . SOC.Jpn., 1979, 52, (7.57.
13' J. K. Whitesell and S. W . Felman, J. Org. Chem., 1980, 45, 755.
(157)
R
OH
(-0
(158)
R
OS0,Me
(159)
ii, MeS0,CI
Reagents: i, Me,CO,H, oxobis-[2,4-pentanedionato-(O,O')]vanadium~1~);
R
Scheme 9
Me Me
Li
(160)
e.g. (160), e.e.'s of up to 31% have been generated. This is claimed to be the first
example of enantioselective deprotonation.
Photochemical and Thermal Reactions of 0xirans.-The photolysis of the @ -
ionone-type compound (161) uia n-v* excitation (A 2 347 nm) gave (162)
(75%) in pentane; in MeOH, however, (163) was the favoured product.13' The
($d
CH2 CH,
(3cH
photochemistry of this system appears to be governed by photoinduced C-C bond
fission of the oxiran.
MeOCMe
(161) (162) (163)
Triplet T -+ v * excitation of a@-epoxy-ketones (164) at 366nm may be

localized at either end of the molecule, depending upon the aromatic groups
For (164; Ar' = 4-MeOC6H4,Ar2 = Ph), localization occurs at the
carbonyl end, and (165; Ar' = 4-MeOC6H4, Ar2 = Ph) is the major product
(64%), together with a trace of benzaldehyde, presumably from fragmentation of
an ylide intermediate. For (164; Ar' = Ph, Ar2 = 1-naphthyl), however, the
triplet excitation is localized at the other end, and 1-naphthaldehyde is the major
product (75%),with minor amounts (8%)of (166; Ar' = Ph, Ar2 = 1-naphthyl).
That the aldehydes arise from ylide intermediates has been shown by irradiation
of (164; Ar' = Ph, Ar2 = 1-naphthyl) in the presence of maleic anhydride.l3'
The isolation of adduct (167) (33%) effectively proved the intermediacy of an
ylide.
X-Ray structure determinations have proved unequivocally that it is the
em-isomer of epoxynaphthoquinone, i.e. (168), which undergoes rearrangement
B. Frei, H. R. Wolf, and 0. Jeger, Helu. Chim. Acta, 1979,62,1645
13' P. Hallett, J . Muzart, and J. P. Pete, Tetrahedron Lett., 1979,2723.
P. Hallett, J . Muzart, and J . P. Pete, Tetrahedron Lett., 1979, 2727.
to (169) in s~n1ight.l~"
The endo-epoxide is inert under these conditions. A
number of photochemical hydrogen-abstraction reactions of epoxy-
naphthoquinones in the presence of xanthene have been d e ~ c r i b e d . ' ~In' ben-
zene, irradiation of (170) gave (171; @-OH), (171; P-OH), (172; R = 9-
xanthenyl) and (172; R = H).
a; GH
\
0
Me
&Me
\
OH
COMe
\
0
Me
(170) 1171) (172)

The diastereoisomeric py-epoxy-ketones (173) and (174) show no stereo-
ax..a
electronic control during photochemical ring-opening, in benzene (A > 280 nm),
since both ketones yield the same products (175) and (176) at the same rate.'42It
has been suggested that a resonance-stabilized intermediate (177) is common to
these reactions.
9.
Y' (175)
(173) X = CH2, Y = 0
(174) X = 0 , Y = CH2
140 R. G . Giles, I. R. Green, R. K. Peter, C. L. Raston, and A. H. White, J. Chem. Soc., Perkin Trans. 1 ,
1979,719.
14' K. Maruyama, S. Arakawa, A. Osuka, and H. Hitomi, Kagaku Toronkai Koen Yoshishu, 1979, 24
(Chem. Abstr., 1980, 92, 197 663).
142 S. Ayral-Kaloustian and W. G . Agosta, J. A m . Chem. Soc., 1980. 102, 314.
The vinyl spiro-oxirans cis- and trans-(178; n = 2 or 4,R = CN; and n = 3,

R = C0,Me or CN) underwent stereoselective cyclizations above 180 "C to give
mixtures (56-68%) containing predominantly !runs- and cis- isomers of the
dihydrofuran (179).14? In a similar reaction, the oxiran (180), on heating to
170°C, gave (181) in 66% yield at 30% conversion.144
.Ph 0
-'
,y H
'CN
Reactions of Oxirans with Organometallic Compounds.-Interest has been

shown in the synthesis of cyclic carbonates (182; R',R2 = various alkyl sub-
stituents or H) by the direct reaction of CO, with oxirans. The reaction may be
achieved using Et4NBr,I4' but the majority of methods reported use organo-
metallic catalysts. Propene carbonate (182; R' = H, R2 = Me) was obtained by
treating CO, with tetraphenylporphinatoaluminium methoxide and l-methyl-
imidazole, followed by propene 0 ~ i d e . I ~Using
' a mixed catalyst of MoCI, and
Ph3P (1:6) and CO, (1 atm), (182; R' = H, R2 = Me) (90-100°/~) was obtained
in 7 High yields of ethene carbonate have been obtained by using either
organotin halides R,SnX,-,, (R = alkyl or aryl, X = Br or C1, n = 2 or 1)148 or
quinquevalent antimony complexes, e.g. Ph,Sb or Ph3SbC12,149 to catalyse the
reaction of ethene and C 0 2 at 60-120 "C.
Two methods for the conversion of cyclic and acyclic oxirans into silyl ether
derivatives of allylic alcohols via organosilicon reagents have been reported.
Using CF,SO,SiMe, and 1,5-diazabicyclo[5.4.0] undec-5-ene (1 : l), in benzene
or toluene, the cyclic oxirans (183; n = 1, 2, or 3) were converted into (184;
R = SiMe,; n = 1, 2, or 3) in 59, 88, and 100% yields;"' (183; n = 4)
underwent transannular ring-closure to (185) (100%) under these conditions. An
alternative for such conversions is ISiMe2Bu' with 1,5-diazabicyclo[4.3.0]non-5-
ene, which gives (184; R = SiMe,Bu'; n = 1, 2, 3, or 4) (68-90%), with no
transannular cyclization products.1S1This is claimed to be the more general
technique, being applicable to both mono- and di-substituted oxirans, which are
systems which give poor yields with the former reagents. Highly stereospecific
ring-opening to allylic alcohols has been achieved, using organoaluminium
amides;"* rrans-(183; n = 8) could be converted quantitatively into (E)-(184;
R = H, n = 8), using dimethylaluminium 2,2,6,6-tetramethylpiperidide,
whereas the cis-isomer gave only an 8% yield.
143 W. Eberbach and W. Seiler, Terrahedron Lett., 1978, 4875.
144 W. Eberbach, J. Brokatzky, and H . Fritz, Angew. Chem., I n [ . Ed. Engl., 1980, 19, 47.
14' C. H. McMullen, J. R. Nelson, B . C. Ream, and J . A. Sims, Ger. Offen. 2 855 232 (Chern. Abstr.,
1979, 91, 140 363).
I46
N. Takeda and S . Inoue, Bull. Chem. SOC.J p n . , 1978, 51, 3564.
14' M. Ratzenhofer a n d H . Kisch, Angew. Chem., Int. Ed. Engl., 1980, 19, 302.
'41 H. Matsuda, A. Ninagawa, R. Nomura, and T . Tsuchida, Chern. Left., 1979, 573.
149 H. Matsuda, A. Ninagawa, and R. Nomura, Chem. Letr., 1979, 1261.
150 S. Murata, M. Suzuki, and R. Noyori, J. A m . Chem. Soc., 1979, 101,2738.
15' M. R. Detty, J. Org. Chern., 1980, 45, 924.
15* A . Yasuda, H. Yamamoto, and H . Nozaki, Bid/. Chem. SOC.Jpri., 1979, 52, 1705.
Rj=-t2 ( C P ( C U O R zI (J-'"."''
O K
0 0
(183) (184)
(182) (185)
A novel ring-opening reaction of oxirans, catalysed by copper and pyridine,
generates cis-diols under mild condition^.'^^ The bicyclic epoxides (186; n = 1
or 2) yield (187; n = 1) (95%) and (187; n = 2) (85%) in neutral, phosphate-
buffered, solution. This type of reaction may have some relevance to the
metabolic pathways for fused aromatic compounds, which are thought to proceed
via arene oxides and diol epoxides. The catalyst system may be used to add OH-,
C1-, or MeO- regiospecifically to the benzylic centre of indene oxide, with proton
addition to the oxygen atom of oxiran.
R
(186) R R = 0
(187) R = OH
Miscellaneous Reactions of 0xirans.-The first successful enzymatic cyclization

of a non-natural squalene has been (18Z)-Oxidosqualene (188),
which does not possess the naturally occurring all-trans stereochemistry, was
caused to cyclize, in the presence of 2,3-epoxysqualene sterol cyclase, to (20s)-
epinorlanosterol (189). The polyene oxide (190) underwent an uncommon
tricyclization in CH,Cl, containing BF,.OEt, to form the cis-fused A/B-ring
18-nor-steroid (191) (~S'/O);''' this compound was found to be identical with a
material derived by treatment of a naturally occurring steroid with BF3.
153 M. Imuta and H . Ziffer, J. Am. Chem. Soc., 1979, 101, 3990.
Is4 M. Herin, P. Sandra, and A. Krief, Tetrahedron Lett., 1979, 3103.
E. E. Van Tamelen and D. G . Loughhead, J. Am. Chem. Soc., 1980,102,869.
Nucleophilic ring-opening reactions of (192; R ' = R' = H), (192; R ' = Br,
R2 = Me), and (192; R' = Me, R2 = Br) take place by attack at C-7.'sh.'57Thus
(192; R ' = Br, R2 = Me), with HI, gives the corresponding iodohydrin, which
could be acetylated and dehydrohalogenated with Et,N or with KOAc plus
18-crown-6 to yield a-methylene-lactones (193; R' = H, R2 = OAc) and (193;
R' = OAc, R2 = H) that are of potential cytotoxic interest.
*
(192) (193)
Two high-yield three-step syntheses of (195) from anthraquinone have been

developed uia the bis-epoxide (194) (67% and 89% Compound (195)
was obtained from (194) either by conversion into lO-hydroxymethyl-9-
anthraldehyde with LiBr, followed by oxidation, or by conversion into 9,lO-
dihydroanthracene-9,lO-dicarboxaldehyde with BF,, followed by dehydrogena-
tion.
\ / @\ / o
+
J-
Br
0 CHO
(194) (195) (196)
Oxirans may be converted into a-chloro- or a - bromo-ketones o n reaction with
Me2iX X- (X = , C l or B I - ) . ' Sequential
~~ treatment of (183; n = 1 , 2 , or 3) in
CH2CI2with Me2SBr Br- and NEt, gave (196; n = 1 , 2 , or 3) in 80,74, and 68%
yields, respectively.
2 Oxirens
The isomerization of the a -oxo-carbenes (197) and (199) via the oxiren (198) has
been investigated, using labelled diazocarbonyl compounds as carbene sources
(Scheme The distribution of the labelled carbon in the products showed
that the Wolff rearrangement proceeds in both cases, but mainly from (199).
3 Aziridines
The chemistry of aziridines, e.g. their short C-C bond length, their low basicity,
and the high energy barriers to conformational inversion around the nitrogen
156 S. M. Ali, N. M. Crossland, T. V. Lee, S. M. Roberts, and R. F. Newton, J. Chem. SOC.,Perkin

Trans. 1, 1979, 122.
lS7 S. M. Ali, C. B. Chapleo, and S. M. Roberts, J. Chern. Soc., Perkin Trans. 1 , 1979, 126.
Y.-I. Lin, S. A. Lang, C. M. Seifert, R. G. Child, G. 0. Morton, and P. F. Fabio, J. Org. Chem., 1979,
44, 4701.
lS9 G. A. Olah, Y. D. Vankar, and M. Arvanaghi, Tetrahedron Lert., 1979, 3 6 5 3 .
Ih" K. P . Zeller, Liebigs A m . Chon., 1979, 2036.
Me-C-C-H
I1
0
*
II
N*
hv
+
Me-C-c-H
0
II
*
Me-c-C-H
0
*
II - Me-C-C-H
II
N* 0
*
II
Me
\*
J Me
,C=C=O 0
H (198) H
I,
-4 li
M&H,C -OCH2Ph MeCH,?-OCH,Ph
II I\
0 0
Reagents: i, PhCH,OH
Scheme 10
atom, have been briefly reviewed,16' as has the solid-state photochemistry of

aziridines and oxirans.'62
Preparation.-Direct Insertion. The oxidation of 2,4-dinitrobenzenesuIphen-
amide with [Pb(OAc),] in CH2C12generates a nitrene which, in the presence of
alkenes, gives aziridines.lh3 With trans-1 -phenylpropene, [200; R = 2,4-
(NO,),C,H,] (64%) was formed, which could be reduced with NaBH, to (200;
R = H) (56%). Nitrenes produced by the oxidation of N-aminophthalimide
or 3-amino-2-methyl-4-quinazoline with [Pb(OAc),] yield 6-azabicyclo[3.1 .O]-
hexanes, e.g. (20 l),'" in the presence of variously substituted cyclopentenes.
The aziridinopregnene (202) was formed, in 15o/' yield, from the reaction of
photogenerated carbethoxynitrene with the parent steroidal diene.'"
dN-ND &co2Et COMe
Me
N
R \
0 AcO
(200) (201) (202)
Decomposition of the sodium salt of the tosylhydrazone (203) in refluxing CCI,

produces a diazomethane intermediate which undergoes an internal insertion
reaction to form (204) (73%).16' The normal reaction of diazomethane-type
intermediates with double bonds would be 1,3-cycloaddition; the reaction
16' Y. Hata, Kagaku ( K y o t o ) , 1979, 34, 695 (Chem. Abstr., 1980, 92, 198 170).
16' A . M. Trozzolo, A. S. Sarpotdar, T. M. Leslie, R. L. Hartless, a n d T. Dominh, Mol. Crysf.Liq. Cryst.,
1979, 50, 201 (Chem. Abstr., 1979, 91, 192 006).
163 R. S. Atkinson and B. D. Judkins, J. Ctiem. Soc., Chem. Commun., 1979, 832.
lb4 G. R. Meyer, C. A. Kellert, and R. W. Ebert, J . Hetcmcpcl. Chem., 1979, 16, 461.
165 A . V. Karnernitskii, Z . 1. Istomina, E. P. Serebryakov,andA. M.Turuta, Zzu. Aknd. NorrkSSSR, Ser.
Khim., 1979, 186 (Chem. Absrr., 1979, 91, 20 886).
Y. Nishizawa. T. Miyashi, and T. Mukai, J. A m . Chem. Soc., 1980, 102, 1176.
CI
described above represents the first report of a nitrene- type 1,l -cycloaddition
reaction of such a species.
Addition of dichlorocarbene to the imines of the respective ketones gives
the spiro-aziridines (205; X = a bond or CH,CH,; R = H, 4-MeC&, or 1-
napht h yl) .16'
Preparation of Aziridines by Cyclization. A most useful general method for the
high-yield syntheses of a variety of 0 or N heterocyclic systems from the
cyclization of diols or amino-alcohols, respectively, has been reported.'68
Treatment of diols with a mixture of Et02CN=NC0,Et and PPh3 causes
cyclization to three- or seven-membered rings. In the case of 2-amino-2-methyl-
propane (206), a quantitative yield of 2,2-dimethylaziridine (208) is obtained via
the intermediate (207) (Scheme 11). It has been suggested that intermediates of
this type are general for such cyclizations.
H N : dY HN
y+ Ph,PO
NH, '1' I
; rnnL
rn3
(206) EtO . EtO2CNHNHCO2Et
I
NHC0,Et
(207)
Scheme 11
A rather older procedure for the cyclization of p -amino-alcohols under mild

conditions involves the simultaneous action of PPh3, CC14, and Et3N.lh9This
method was used for the conversion of (209) into (210) as part of a preliminary
investigation into the synthesis of mitornycin~.~'~)
YMe
M. A. Abou-Gharbia a n d P. H. Doukas, Heterocycles, 1979, 12, 631.
"* J. T. Carlock and M. P. Mack, Tetrahedron Lett., 1978, 5153.
I69
R. Appel and R. Kleinstuck, Chern. Ber., 1974, 107, 5 .
170
T. Kametani, Y . Kigawa, and M . Ihara, Terrahedron, 1979, 35, 313.
S-Ethenyl-sulphoximine derivatives have found use in the synthesis of aziri-

dines (2l3).I7’ The salts (211; R’ = R’ = H, Me, or Ph) and (211; R’ = H,
R2 = Ph) act as ethene-transfer reagents when treated with R3NH2( R 3 = Me,
But, Me,CCH2Ph, or 4-MeC6H4)in THF. The suggested mechanism (Scheme 12)
involves initial Michael attack on the salt to give (212),followed by cyclization to
form (213).
J - )
o+S +
H
Ph” ‘NMe,
R2
BF4-
+ R”NH2 + o+g
Ph’
cc-:l’
S+
‘NMe,
R2 --*
0
II
PhSNMe,
R3
N
+ *“I
R2
(212) (213)
Scheme 12
The Ritter reaction of 3P-chloro-5,6a -epoxy-Sa -cholestane (214) with

MeCN in the presence of RF,.0Et2 gave a mixture of ring-opened products from
which the 5-hydroxy-6~-acetamido-compound was ~ b t a i n e d . ’ ~Cyclization
’ of
this material in refluxing EtOH containing NaOH gave the 5,6@-aziridino-
cholestane (215). Similarly, the 5,6P-epoxide could be converted into the cor-
responding 5,6a -aziridine.
Preparation of’Aziridines via Ring Contraction. The aziridines (217; R’ = Me;

R2 = Me, 4-MeC6H4,Et, Pr’, or Ph,CH) and (217; R’ = Et, R2 = Et or Pr’) are
not easily obtained, but have now been synthesized from the 0-alkyl oxime
ethers of (CO,R’),CO.”’ Addition of diazomethane to the oxime ether gave
(216), which decomposed to (217) either with acid or else on thermolysis or
primary photolysis. Triazolines (2 18) also underwent thermolysis to produce
aziridines (219; R’ = Ph or PhCH2, R2 = CN or C02Me , R3 = C02Me).174
17’ C. R. Johnson, J. P. Lockard, and E. R. Kennedy, J. Org. Chem., 1980, 45, 264.
G. M. A. Shafiullah, Synth. Cornmiin., 1979, 9, 677.
’73 R. G. Kostyanovskii, A. V. Prosyanik, A. I. Mishchenko, G. V. Shustov, I. I. Chervin, N . L.
Zaichenko, A. P. Pleshkova, P. N. Belov, and V. I. Markov, Izv. Akud. Nuuk SSSR, Scr. Khim.,
1979, 1780 ( C h e m . Absfr., 1980, 92, 6323).
!7 4
M . S. Ouali. M. Vaultier, and Ii. Carrie, Bull. SOC.Chim. Fr., Purr 2, 1979, 633.
When refluxed in T H F with a molar quantity of LiAlH4, (220) gave the

zwitterionic aziridine (221) (55'/0).'~'Prolonged reaction time (3.5 h), however,
resulted in increased yields of the ring-opened products (222; X = H, or 0)
(85%). C N D 0 / 2 calculations were reported for the ring-contraction, which is
thought to proceed uia a concerted[ 1,3]-sigmatropic migration of the nitrogen to
a carbon of the enolate anion that is formed when a bond ruptures.
Chiral Aziridines.-The optically active aziridines [224; R = H, Me, Ph, 4-
MeOC6H4,or 3,4-(Me0)2C6H3] were prepared by heating (223) with N ~ O E L ' ~ ~
Each asymmetric carbon was of S configuration, and 'H n.m.r. spectra indicated
that compounds (224) exist predominantly as the trans-conformers.
/CH2R
0
MeC,
1 C0,Et
R'Cot
N
N H
u.
'CHPhOH
I1
NH
The reaction of R'COCH=CHR2 (R' = Ph or Me, R2 = Ph or COPh) with

(+)-(225) in MeOH gave chiral 2-acyl-aziridines (226).'77Thus trans- 1-benzoyl-
2-phenylethene, after reaction with (+)-(225)in MeOH at room temperature for
6 days, gave (-)-(2R,3R)-trans-(226; R ' = R2 = Ph) (55%)with 30.4"/0 optical
yield.
Studies of the circular dichroism of (S)-pyrazinoyl-aziridines (227; R = H, Me,
Pr', or PhCH2) revealed similar spectra, and indicated that all have similar
conformational e q ~ i l i b r i a .These
' ~ ~ equilibria are associated with rapid inversion
of nitrogen and rapid rotation around the N-CO bond, this being supported by
' H n.m.r. studies.
(227) (228)
"' G. Chidichimo, G. Cum, F. Lelj, G. Sindona, and N. Uccella, J. A m . Chem. Soc., 1980, 102, 1372.
'76 K. Weinges and G. Brune, Chem. Ber., 1980, 113, 722.
'71 S. Oae, N. Furukawa, T. Yoshimura, and T. Akasaka, Jpn. Kokai Tokkyo Koho 79 39 067 (Cliem.
Abstr., 1979, 91, 91 486).
17' M. M. El-Abadelah, S. S. Sabri, A. A. Jarrar, and M. H. A. Zarga, J. Ciietn. SOC.,
Perkin Trans. I,
1979, 2881.
The invertomers of (228) have been separated by gas chromatography on a

column coated with optically active nickel(I1) bis-3-heptafluorobutanyl-( 1R)-
camphorate in ~ q u a 1 e n e . The
l ~ ~ chiral invertomers gave two distinct peaks, of
intensity 1 : 1.
Spectroscopic Studies of Aziridines.-A review of stereostructural investigations
of trans- and cis-l-alkyl-2-aryl(alkyl)-2-carboaziridines by 'H and "C n.m.r.
spectroscopy has been published.'80
The distribution of invertomers and the thermodynamic parameters for con-
formational inversion of C-unsubstituted aziridines have been determined by
250 MHz 'H n.m.r. spectroscopy.'" The steric hindrance of the aromatic group in
C-aryl-aziridines with other ring substituents was found to be consistent with
some form of conjugation between the aromatic system and the aziridine ring.
The 'sN-'3C spin-spin coupling constants for cis- and trans-1 -cyclohexyl-2-
phenyl-3-benzoylaziridines (229)18* are in good agreement with theoretical
predictions.'83 Determined endocyclic 'J(15N,13C)values average out at 7.1 Hz,
compared with the predicted value of 7.9 Hz, suggesting that the N-C bonds of
the ring have high p character. The mass spectrum for this system has been
reported to involve initial ionization followed by ring-opening and loss of HO to
form a stable ion that has the 4-phenylisoquinilinium ~ t r u c t u r e . ' ~ ~
Ph
v C O P h R4
Y w+
0
(229) (230) (231 )
N
H
(232)
The '5N-31Pcouplings for a series of cyclic phosphoramidates (230; R' = R2 =

R3 = R4 = H or Me) ranged from 10.6 Hz for (230; R' = R' = H, R2 = R" =
Me) to a1 Hz for (230; R' = R2 = R' = R4 = Me).IX5A significant rise in the
coupling was noted as the ring size of the heterocycle was increased to (231;
n = 1) (20.9 Hz) and (231; n = 2-6) (-40 Hz). This increase may be attrib-
uted to the change from pyramidal (sp3) nitrogen in aziridines to trigonal (sp')
nitrogen in the larger ring compounds.
Collision-induced dissociations have indicated that the M+ radical cation
species that is formed in the mass spectrum of aziridine has structure (232).IXh
Gaseous stable aziridinium ions have been formed from the 2-
phenoxyethanamine molecular ions.'87
V. Schurig, W. Buerkle, A. Zlatkis, and C. F. Poole, Nuturwissenschuften, 1979, 66, 423 (Chem.
Absrr., 1979, 91, 192 690).
180
P. Tarburton, C. A. Kingsbury, and N. H. Cromwell, Stud. Org. Chem. (Amsterdam), 1979,3 (New
Trends Heterocycl. Chem.) 112.
"' A. Lopez, M. M. Gauthier, R. Martino, and A. Lattes, Org. Mugn. Reson., 1979, 12, 418.
182 P. Tarburton, J . P. Edasery, C. A . Kingsbury, A. E. Sopchik, and N. H. Cromwell, J. Org. Chem.,
1979 , 442041.
R. E. Wasylishen, Can. J. Chem., 1976, 54, 833.
184
P. Tarburton, T. Sung, N. H. Cromwell, and M. L. Gross, Org. M a w Spectrom., 1979, 14, 564.
G. A. Gray, G . W. Buchanan, and F. G. Morin, J . Org. Chem., 1979, 44, 1768.
A. Maquestiau, Y. Van Haverbeke, R. Flammang, and A. Menu, Bull. Soc. Chim. Belg., 1979, 88,
53.
"' C. C. Van de Sande, Z. S. Ahmad, F. Borchers, and K. Levson, Org. Muss Spectrom., 1978,13,666.
The populations of N invertomers for a number of unsymmetrically substituted

aziridines were determined by a quantitative analysis of N--H or N --D overtone
bands in their i.r. spectra.18' Thermodynamic parameters were also determined
for cis- 2,3-dimethylaziridine, the syn-anti equilibrium yielding AH =
2.7 kJ mol-' and AGe = 4.7 kJ mol-'.
Reactions of Aziridines.-Photochemical and Thermal. The solid-state photo-
chemistry of aziridines (and oxirans) has been reviewed, both systems yielding
highly coloured ylide intermediates.lR9 A theoretical ub initio SCF-CI approach
has been used in an investigation of the photochemical behaviour of a z i r i d i n e ~ . ~ ~ ~ )
It has been suggested that, in the gas phase, fission of C-N bonds is favoured
whereas C-C bond fission competes in protic solvents.
Aziridinyl-imines may be considered to be masked diazo-compounds; they are
cleaved thermally without the addition of external base, and thus have an
advantage over tosylhydrazones as precursors of d i a z ~ a l k a n e sThermolysis
.~~~ of
the tosylhydrazone salt of (233) at 120 "C gave a high yield of (235), and it was
proposed that (234) was the intermediate.192This pathway was confirmed by the
thermolysis of (236) at 80 OC, which gave (234) (75%).
CH=NX
(233) X = NHTs (234) (235)

Ph
(236) X = Nf
'Ph
A number of tricyclic aziridines (237; R = H, Me02C, or CN) underwent
thermolysis to (239) at temperatures between 80 and 18OoC, the higher
temperature being required for electron-withdrawing ~ u b s t i t u e n t s . ' ~
The
~
reaction is thought to proceed through the intermediate (238). endo- Aziridines
did not undergo this rearrangement under these reaction conditions.
R I
S02Ph
(237)
(239)
The rose-bengal-sensitized photo-oxygenation of aziridines (240) in MeOH
gave phthalimide (242) (51%) as the only isolable The mechanism
la' F. Imberlin, A. Lopez, R. Martino, A. Lattes, and R. Mathis, Spectruchim. Acta, Purr A, 1979, 35,
1033.
A. M. Trozzolo, T. M. Leslie, A. S. Sarpotdar, R. D. Small, G. J. Ferraudi, M . T. Do, and R. L.
Hartless, Pure A p p l . Chem., 1979, 51, 261.
'91 R . Bigot, A. Devaquet, and A. Sevin, J. Org. Chem., 1980, 45, 97.
lgl D. Felix, R. K. Muller, U. Horn, R. Joos, J . Schreiber, and A. Eschenmoser, Helu. Chim. A d a , 1972,
55, 1276.
'91 A . Padwa and H. Ku, Tetrahedron Lett., 1979, 4425.
193 K. Umano, H. Taniguchi, H. Inoue, and E. Imoto, Tetrahedron Lett., 1979, 247.
194 V. Bhat and M. V. George, J. Org. Chem., 1979, 45, 3288.
Ph
hv 0 2
L
7
H
C6H 1 1
o J
0 N H
\
(242) 1
Scheme 13
proposed (Scheme 13) shows the addition of singlet oxygen as a dipolarophile to

(241), and had been suggested previously, when 0, and acetylenic dipolarophiles
were found to add to irradiated (240).'95
Reactions with Retention of the Aziridine Ring. 2-Cyanoaziridine (243; R' = CN,
R2 = H) is stable to H 2 0 at room temperature, but gave the carboxamide (243;
R' = CONH2, R2 = H) o n addition of cyclohexanone, uia the intermediate
(244).196In the absence of water, (245) was formed, but refluxing (243; R' =
CONH2, R2 = H ) with cyclohexanone gave (246).
Treatment of (243; R' = CN, R2 = H) with CIC0,Ph gave (243; R' = CN,
R2 = C0,Ph) (67%); this, with NH3, gave (243; R' = CN, R2 = CONH2).197
The reaction of the acetylenic aldehydes (247; R' = R2 = Me) or [247;
R'R' = (CH,),] with aziridine gave (248), which isomerized to (249).'98
CN NC
b wCONH, Mem
4 0 8 OH
5H
*R'
RI 2
N
(243) (244) (245) (246)
O N
R' OH
R'qC-C--CHO R2.+cd---N3 RR&L=JH 0 OH
OH OH
(247) (248) (249)
A. Padwa and E. Vega, J. Org. Chew., 1975,40, 175.
K . Jaehnisch, E. Schmitz, and E. Gruendemann, J. Prakt. Chew., 1979, 321,712.
19' E. Bosies, R. Heerdt, R. Gall, U. Bicker, and A. E. Ziegler, G e r . Offen 2 656 323 (Chem. Absrr.,
1979,91, 39 299).
'91 A. V. Eremeev, D. A. Tikhomirov, and Yu. V. Shubina, Khim. Geterotsikl. Soedin., 1979, 334
(Chew. Abstr., 1979, 91, 5051).
Three-Me mhered Ring S y ste rns 35
Ring-opening of Aziridirtes to Acyclic Compoi4rads. Nucleophilic ring-opening

with organometallic compounds has been i n ~ e s t i g a t e d .The
' ~ ~ N-substituted
aziridines (250; R = C 0 2 E t ,Ts, or Me) were allowed to react with a selection of
organometallic compounds to determine the best reagents for ring cleavage; for
(250; R = Me), decomposition was the predominant reaction. Of the methyl-
ating reagents, MeLi was unsatisfactory for ring-opening, giving 2-phenyi-
aziridine ( 8 5 % ) from (250; R = C 0 2 E t ) and decomposition with the other
substrates. Ring-opening to (251; R = C0,Me) (48010)and (252; R = Ts) (46%)
was achieved by using MeMgBr and the appropriate aziridine, although a
four-fold excess of the Grignard reagent was necessary in the latter case. The most
efficient reagent was Me2CuLi, which opened (250; R = C02Me) regioselect-
ively to (251; R = C0,Me) (98%) but gave a mixture of (251; R = Ts) (23%)
and (252; R = Ts) (46%)from (250; R = Ts).
Ph R
-Y7
N HNR
R Me
The nucleophilic opening of aziridines has also proved useful in peptide

synthesis. A number of N-tosyl-aziridines (253; R = H, Me, Pr', or Ph) were
opened with phenol or phenate ion in an attempt to introduce the P-phenoxy-
group to amino-acids, such groupings being known to be present in cyclopeptide
alkaloids.200In the case of (253; R = Ph) the ring was regioselectively cleaved to
(254) (100%).
R TrNHqCONHPh
VCONHPh
N
Ts 4-MeC6H,O
(253) (254)
Aziridine peptides (255; Z = PhCH202C)have been used in a novel synthesis

of threonine 0-peptide derivatives (256) by reaction with R-X-OH [R =
PhCH,O,C; X = Gly, Ser, or MeVal: R = Bu'02C; X = Leu, Pro, Phe, Met(O),
Glu(OCH,Ph), Leu-Leu, or ProNMeCH2CO], in 74-97'10 yields, without
racemization.20'The same substrate may also be used in a convenient synthesis of
phosphopeptides via opening with HOP(O)(OCH,Ph),, to give (257; R =
CH2Ph), or with phosphonic acid, to yield (257; R = H).2"2The reactions of
aziridines of this type with primary amines have also been
The reaction of liquid HF with the aziridines (258; R' = H, Me, Et, or Ph; R2,
R3 = H, Me, or Ph) was regio- and stereo-selective, yielding the corresponding
fluoro-amines (259).*04Thus cis- and trans- 1,2-diphenylaziridine gave (259;
'99 A. P. Kozikowski, H. Ishida, and K. Isobe, J. Org. Chem., 1979, 44, 2788.
F. Frappier, F. Rocchiccioli, F.-X. Jarreau, and M. Pais, Tetrahedron, 1978, 34, 291 1.
201
T. Tanaka, K. Nakajima, T. Maeda, A. Nakamura, N. Hayashi, and K . Okawa, BiiII. Chem. SOC.Jpn.,
1979,52, 3579.
202 K. Okawa, M. Yuki, and T. Tanaka, Chern. Lett., 1979, 1085.
203
K . Nakajima, T. Tanaka, K. Morita, and K. Okawa, Bull. Chem. SOC.Jpn., 1980, 53,283.
'04 G . Alvernhe, E. Kozlowska-Gramz, S. Lacombe-Bar, and A. Laurent, Tetrahedron Left.,1978,
5203.
36 He teroc y clic Chemistry
Z-Gly -Thr-Gly -OCH,Ph

I Ph% ,R2 Ph NH,
X
I
R R 1?R3
H
R17-tRJ R2
(256) (258) (259)

R' = R3 = H , R2 = Ph) (95%) and (259; R' = R2 = H,R' = Ph) (100%),
respectively.
The compounds (260; R = H, Me, or Et) (70--85%) are generated photo-
The reaction of
chemically from the corresponding berberinephenolbetaine~.~~)~
(260; R = H) with ClC0,Et in hot benzene gave the spirobenzylisoquinoline
(261; R' = Me, R2 = Cl) (70%),but (260; R = Me) and (260; R = Et) gave the
exocyclic alkenes (261; R'R2 = CH,) and (261; R'R2 = CHMe) quantitatively.
OMe
Formation of Other Ring Systems from Aziridines. The aziridines (262; R' = Ph,
4-C1C6H4, or 4-MeC6H4) reacted with R2NC (R2 = Pr', Ph, But, or
Bu'CH2CMe,) in CH2C12to give the azetidines (263; R' = phthalimido) (40-
4 9 ' / 0 ) . ~The
~ ~ azetidines subsequently yielded acyclic imines after rearrangement.
NRL CONHR CONHR

(263) (264) (265)
An improved synthesis of the pyrrolidinones (265; R = Ph, 4-C1C6H4, 3,4-

CI2C6H3, 1-naphthyl, or Et) from (264) involves their reaction with excess
NaCH(CO,Et), in the absence of
205 M. Hanaoka, S. Yasuda, K . Nagami, K. Okajima, and T. Imanishi, Tetrahedron Lett., 1979, 3749
206 J. Charner, H. Person, and A. Foucaud, Tetrahedron Lett., 1979, 1381.
207 H . Stamm and J . Rudny, ChPrn.-Zrg, 1979, 103, 156 (Chem. Ahsrr., 1979, 91, 74 400).
Three-Membered Ring S y s t e m 37
{u:I> Me
Me
\
C=NNHCO,Et
(267)
N H N HCO Et
'C=NNHCO,E~
{U::p H
(268)
The aziridine ring in (266) is stereospecifically cleaved in AcOH containing
Et02CNHNH2,to produce the oxazolidinones (267) and (268).20s
The iodide-catalysed ring-opening of (269; R = H) gave a quantitative yield of
(270; R' = R2 = H).*09For (269; R = Me) the cyclization produced both (270;
R' = H, R2 = Me) and (270; R' = Me, R2 = H), whereas only (270; R' = H,
R2 = Me) was formed in the reaction in H2S04.
The reaction of (271; R' = H, R2 = H or Me) with ethyl propynoate pro-
ceeded uia Michael addition, to form (271; R' = CH=CHCO,Et), and
subsequent rearrangement to the dihydronaphthalene (272).21n2-Benzoyl-
aziridine (273) and RCH2C0,Et (R = H or Ph) react in the presence of NaH to
provide a novel synthesis of pyridinones (275).2"The original objective of this
study was the synthesis of the azabicyclo[3.1 .O]hexane (274),which was formed as
an intermediate but not isolated from the reaction.
(272) (274) (275)
4 Azirines
The chemistry of azirines and diazirines has been reported as part of a general
review of three-, four-, and seven-membered aza-heterocycles.212Recent aspects
208 Z. I. Istomina and A. M. Turuta, I z v . A k a d . Nauk SSSR, Ser. Khim.. 1979, 2318 (Chem. Abstr.,
1980,92, 147 038).
209 N. P. Peet and P. R . Anzeveno, J. Heterocycl. Chem., 1979,16, 877.
'lo M. Attia, Y. Gelas-Mialhe, and R . Vessiere, Chem. Lett., 1979, 1095.
211 R. Bartnik, A. Laurent, and S. Lesniak, C . R . Hehd. Seances Acad. Sci., Spy. C, 1979, 288, 505.
*I2 R. K. Smalley, Compr. Org. Chem., 1979, 4, 565.
of azirine chernistry2l3 and the reactions of 3-amin0-2H-azirines~'~

have been
surveyed.
Preparation.-A new general synthetic route to the azirines (278; R = Ph,
4-C1C6H4,4-BrC6H4,4MeC6H,, or Me) from the CY -bromo-ketoximes (276) has
been described (Scheme 14)."' A practical advantage of the method is that the
preparation of the oxazaphospholines (277) is accomplished in one pot, with
yields >7O0/0. Isolation and pyrolysis of (277) provides good yields of (278). Using
this method, a number of new (or previously difficult to obtain) azirines have been
prepared, e.g. (278; R = But), (278; R = Me), and ring-deuteriated compounds.
R
(278) (277)
Reagents: i, H i ; ii, PPh,; i i i , H30+;
iv, Et,N; v, heslt
Scheme 14
The photochemically induced isomerization of isoxazole (279) to oxazole (281)

is known to proceed uiu the intermediate keto-azirine (280). An M.O. study of
the isomerization reactions of the azirine that are involved has been reported.*"
Irradiation of (280) at >300 nm gives n + T * excitation of the CO chromophore
to S , , intersystem crossing to T 1 ,and then C-N bond rupture, to form (279).
Irradiation at 254 nm, however, gives n + T * excitation of the C=N chromo-
phore to S 2 , intersystem crossing to T I ,and then C-C bond rupture, to form
(281).Such an isomerization reaction resulted in the photochemical conversion of
isoxazolophane (282) into (283) (40%).2'7Irradiation of (283) at 254 nm
produced a quantitative yield of the expected oxazolophane. A new rearrange-
ment was found, however, on irradiation of (283) at >300nm, when the
acyl-ketenimine (284) was formed, which could be converted into (285) by acid
hydrolysis.
2'3 A. Hassner and V. Alexanian, Stud. Org. Chem. (Amsterdam), 1979, 3 (New Trends Heterocycl.
Chem.), 178.
*I4 H. Heimgartner, Chimici, 1979, 33, 1t1.
2's A. Hassner and V. Alexanian, J. Org. Chem., 1979, 44, 3861.
'Ih H. Tanaka, T. Matsushita, Y. Osamura, and K. Nishimoto, Kokugaku Toronkai Koen Yoshishu,
1979, 176 (Chern. Ahstr., 1980, 92, 197 664).
'I7 S. Albanesi, A . Marchesini, and B. Gloia, Tetrahedron Leu., 1979, 1875.
Reactions of Azirines.-Two groups of workers have investigated the prep-

aration of 2H-pyrroles by the reaction of carbanions with azirines. Laurent et al.
obtained azirines from the action of base on methiodides of NN-dimethyl-
hydrazones; the azirines could be used, without isolation, to provide overall yields
of 65-70% of pyrroles, based on the quaternized hydrazones.21R The azirine
(286; R' = R2 = Me, R3 = Ph) reacted with (287; R4 = H or Me, R5 = H) in
NaH plus DMSO to give (288) (75-80%); a mechanism for this reaction is shown
in Scheme 15. Initial attack of the enolate anion is followed by proton transfer,
ring opening, and cyclization. Padwa et af. have studied the reaction of aceto-
phenone anion, (287; R4 = R' = H), generated in NaH plus DMSO, with
allyl-azirines, e.g. (286; R' = Me, R2 = CH2CH=CH,, R3 = Ph), to yield (288)
R4 R3
Ph 'NH
Ph
(290) 1
I
Scheme 15
*IH A. Laurent, P. Mison, A. Nafti, and N . Pellissier, Tetrahedron Lett., 1978, 4511,
and the subsequent thermolysis of (288) at 175 "C to produce (289; R2 = Me,
R3 = Ph, R4 = CH2CH=CH2).,l9 In a subsequent investigation by the French
group it was found that (286; R' = H, R2 = Me, R' = Ph) reacted with benzyl
ketones (287; R4 = H or Me, Rs = Ph) to give predominantly the amides
(291).220The proposed mechanism starts with the same attack by a carbanion but
is followed by an intramolecular cyclization, to form the l-azabicyclo-
[2.1.O]pentane intermediate (290), and subsequent ring-opening.
A number of reactions of the azirine (292) have been reported (Scheme 16).
With (293; R' = Ph or 4-MeC6H4),the amidines (294) are formed; these readily
rearrange to imidazolinones (295).22' Addition of phenyl isocyanate or
diphenylketen to (292) gave (296) and (297) respectively.222The reaction of (292)
with the meso-ionic oxazoles (298) or the dithiole (299) gave ( E l - and (Zb(300)
or (301),respectively.223
R'SO,
I
NMe,
(294)
- poMe,N
-N
I
(295) R'0,SNCO
NMe, (293)
I
5
R
(297)R = Ph
Me,C -C=NPh
PhNvNPh
I
II
Ph
0-
N Ph Ph
z>
0.-
'S
(299)
Ph
0
(300) R = NMeCOPh
(296)
(301) R = SCSPh
Reagents: i, (293); ii, PhNCO; iii, Ph,C=C=O; iv, (298); v, (299)
Scheme 16
Heterocycles may also be formed by the opening of azirines with amines; thus
(302), with NH3, is cyclized to (303) (72%), although only the ring-opened
product (304) was obtained by using MeNH2.224With amino-acid esters
RCH(NH2)C0,Me (R = H, Me, Pr', PhCH2, CH2C02Me,CH2CH2C02Me,or
3-indolyl), the azirine (302) gave pyrazinones (305) (35-75'/0).~~' The reaction
of (302) and MeO2CC_CCO2Me in the presence of [Mo(CO),] gave (306)
(28%); without the alkyne, pyrazines were formed.22h
A novel method for the synthesis of aliphatic PP-difluoro-a- amino-acid esters
(308; R' = Me, R2 = Et) and (308; R' = Ph, R2 = Me) ( 3 2 4 3 % ) involves
219 A. Padwa and Y . Kulkarni, Tetrahedron Lett., 1979, 107.

220 A . Laurent, P. Mison, A . Nafti, and N. Pellissier, Tetrahedron Lett., 1979, 3955.
*" E. Schaumann and S . Grabley, Chem. Ber., 1980,113, 934.
222 G. Mukherjee-Mueller, H. Heimgartner, and H. Schmid, Helu. Chim. Acta, 1979, 62, 1429.
223 J . Lukac and H. Heimgartner, Helv. Chim. Acta, 1979,62, 1236.
224 A. V. Eremeev, R. S. El'kinson, M. Magi, and E. Liepins, Khim. Geterotsikl. Soedin., 1979, 1352
(Chem. Ahsrr., 1980, 92, 94 346).
225 A. V. Eremeev, R. S. El'kinson, and V. Imuns, Khim. Geterotsikl. Soedrn., 1979,988 (Chem. Ahstr.,
1979, 91, 157 689).
226 A. Inada. H. Heimgartner, and H. Schmidt, Telrahedron Lett., 1979, 2983.
(302) R = Me
N
(309) RR = (CH,),
R
Ph
H2N
phq z"w"
I:->;'" I3
(303) (304)
NH2 Ph N
(305)
R 'CF2CHCO R
R&co2Rz
N i
PhCOCFRz
cleavage of the azirinecarboxylate (307) with H F in ~ y r i d i n e . ~Good

~ ' yields of
a-fluoro-ketones (310; R = Me) and [310; RR = (CH2)5]have been obtained
on treating (309) with Olah's reagent and subsequent
The azirine (311; R3 = Me) has been shown to react with the Reformatskii
reagents (312; R' = R2 = H or Me; or R' = H, R2 = Me) to give the aziridines
(313) (65--81°/0).228 However, (311; R3 = H) gave only 31-59% of the cor-
responding aziridine, together with the diazepinones (314) (2-22%).
Ph Me R
R' OEt
Ph )-+
RZ / O
R'xW.R, N R2
Ph
N ZnBr Et0,C R2 H 0 H Me
Treatment of the 2-aryl-azirines (315; R' = H, Br, Me, or MeO; R3 = H) and

(315; R' = Me, R2 = H) with [Rh(CO),CI], and CO (1 alm) at room tempera-
ture or 5 "C gave good yields of the highly reactive vinyl isocyanates (316).229
5 Thiirans
A book on the chemistry of thiirans has been published230and two reviews on
thiiranium ions have
227
T. N. Wade and R. Guedj, Tetrahedron Lett., 1979, 3953.
228
B. Kryczka, A. Laurent, and B. Marquet, Tetrahedron, 1978, 34, 3291.
229
T. Sakakibara and H. Aiper, J. Chem. SOC.,Chem. Commun., 1979,458.
230
A. V. Fokin and A. F. Kolomiets, 'Chemistry of Thiiranes', Nauka, Moscow, 1978 (Chem. Abstr.,
1979,91, 140 705).
23 1
V. N. Gogte and H . M. Modak, Stud. Org. Chem. (Amsterdam), 1979, 3 (New Trends Heterocycl.
Chem.), 142.
232
V. A. Smit, N. S. Zefirov, I . V. Bodrikov, and M. Z. Krimer, Acc. Chem. Res., 1979,12,282.
Preparation.-Flash vacuum pyrolysis of 1,3-oxathiolan-5-ones causes loss of

C 0 2 with the concomitant formation of the corresponding thiirans in nearly
quantitative The reaction is stereospecific, and proceeds with inversion
of configuration; thus (317) in which the cis : truns ratio is 62 :38 is converted into
(319) (91%) in which the cis: truns ratio is 35 : 65. Thiocarbonyl ylides, e.g. (318),
are intermediates in this process.
0
heat
,l,f:A -, S
Ph T'ph[='[Ph
(317) s
(318) P j (319)
'c1
(320)
A new method for the preparation of thiirans from alkenes employs suc-
cinimide- or phthalimide-N-sulphenyl chlorides to form addition compounds,
e.g. (320; n = 1, 2, or 4), which, on treatment with LiAlH, at -78 "C, give the
corresponding cycloalkene sulphides (58-97 The method has also been
successfully applied to the preparation of thiirans from styrene, methylene-
cyclohexane, and norbornene.
The first preparations of optically active thiirancarboxylic acids have been
Treatment of the cysteine esters (R)-(321; R = Me) with NaNO,
and HCl causes deaminative cyclization to chiral (S)-(322; R = Me). For the
parent acid (R)-(321;R = H), optical yieldsof (S)-(322;R = H) of 53 and 60%
*&&
were obtained in dilute HCI or MeC02H, respectively.
I SH
C
CH,
R 0 2 C t 7 S
H,N(A'CO,R
s N=N N==N
(321) (322) (323) (324) (325)
Tetrasubstituted thiirans (324; R' = H, R2 = H, Me, But, CO,Et, or Ph) and

(324; R' = R2 = Me) (74-100%) have been synthesized by the reaction of
pyrazolinethione (323) with the corresponding diazo-compound R'R2CN2.23h
Elemental sulphur has been found to react with polycyclic alkenes to give
1,2,3-trithiolans, but in the particular reaction of sulphur with bicyclohepta-2,5-
diene the exo-sulphide (325) (10%)has been obtained for the first time.237
Reactions of Thiirans.-A synthesis of thiazines [327; R' = alkyl; R2 = H,
R3 = Me or CH(OEt),, or R2R3 = (CH2),] involves nucleophilic ring-opening of
the thiiran (326) by a lithio-isocyanide (LiCHR'NC) to produce the correspond-
ing acyclic thiol and subsequent closure to (327), using Cu2O in benzene.238
*" T. B. Cameron and H. W. Pinnick, J. A m . Chem. Soc., 1980, 102, 744.
234 M. U. Bombala and S. V. Ley, J. Chem. SOC.,Perkin Trans. 1, 1979, 3013.
"' C. D. Maycock and R. J. Stoodley, J. Chern. SOC.,Perkin Trans. 1, 1979, 1852.
236 R. J. Bushby and M. D. Pollard, J. Chem. SOC.,Perkin Trans. 1, 1979, 2401.
237 J. Emsley, D. W. Griffiths, and G . J . J . Jayne, J. Chem. Soc., Perkin Trans. I, 1979, 228.
238 U . Schoellkopf, R. Jentsch, and K. Madawinata, Liebigs A n n . Chem., 1979, 45 1 .
R2 R i q R '
S R2 Et02C C0,Et
(326) (327) (328)
Styrene was obtained when (326; R2 = H, R3 = Ph) was treated with lithio-
isocyanides, and (328) was obtained from the reaction of LiCH(NC)CO,Et with
(326; R2 = H, R' = Me).
Three possible modes of cycloaddition can be envisaged for the reactions of
(329). These are ( a ) initial Ph2C-S bond cleavage followed by addition, ( h )
addition across S-C=N, and (c) addition across C-C=N."" All three modes
have been realized experimentally in the conversions of (329) into ( a ) (330)
(70%), with trans-PhCH=CHNMe2, ( b )(331 ) (28%), with MeCrCNEt,, and
(c) (332; R = Me, Ph, or 3-N02C6H,) (l2-68%), with RCHO.
Excited sulphur atoms S('D2),from the U.V.photolysis of COS in sitic, react

with ethene to yield thiiran and vinylthiol in 1OO0/o yield.2'" The vinylthiol is
formed via direct insertion into a C-H bond and by unimolecular isomerization
of the chemically activated ground-state thiiran. This novel thiiran vinylthiol +
rearrangement is analogous to the cyclopropane +
propene rearrangement in
the sense that both proceed concertedly via a bicyclic activated complex.
Kinetic analysis of the ring-opening reactions of methylthiiran and methyl-
oxiran with Bun2NHin mixed solvents containing DMSO has been
Methyithiiran was more reactive under these conditions, owing to the selective
solvation of thiolate anions in DMSO in the transition state.
The Chemistry of Thiiranium Ions.-A group of Russian workers have published
several papers concerning the preparation of thiiranium ions (333) from alkenes
and their nucleophilic opening reactions. The addition of sulphonyl bromide
(RSBr) to propene, followed by cyclization with AgSbF6 or AgBF4, gave [333;
R ' = Ph, 4-MeCsH4, 2,4,6-Me,ChH2, 4-C1C6H4, 4-CF3ChH4, or 2,4-
(N02)2C6H3; R2 = Me; R3 = H; X = SbF6 or BF4].242 Treating butadiene with
R'S'BF4- gave (333; R' = Me, Ph, 4-MeC,H4, 4-CIC6H4, 2,4,6-Me,C6H2,
4-CF3ChH4,or C,F,; R2 = H; R' = CH=CH2; X = BF4).243When cis-cyclo-
239
G. L'abbe, J.-P. Dekerk, S. Toppet, J.-P. Declercq, G. Germain, and M. Van Meerssche, Tetrahedron
Lett., 1979, 1819.
240
A. G . Sherwood, I. Safarik, B. Verkoczy, G Almadi, H. A. Wiebe, and 0. P. Strausz, J. A m . Chem.
Sqc., 1979, 101, 3000.
241
H. Kakiuchi, T. Iijima, and H. Horie, Tetrahedron, 1979, 35, 303.
242
A. S. Gybin, M. Z. Krimer, V. A. Srnit, V. S. Bogdanov, and E. A. Vorob'eva, I Z U .A k a d . Nauk
SSSR, Ser. Khim., 1979, 563 (Chem. Abstr., 1979, 91, 20204).
243
Yu. B. Kal'yan, M. Z . Krimer, and V. A. Smit, Izv. A k a d . Nairk SSSR, Srr. Khrnr., 1979, 2300
(Chem. Abstr., 1980, 92, 146 389).
+
octene was allowed to react with RIS(SR'), X , generated from R',S2 and SbCI,
at -78 "C, a good yield of [333; R' = 4-ClC6H4,4-MeC6H4,or 2,4,6-Me,C,H2;
R2R3 = (CH,),; X = SbCI,] was
(333) (334) (335) (336)
6 Thiirens
The chemistry of thiirenium ions has been reviewed.24sTwo groups have been
involved in a discussion concerning the i r. spectrum of thiiren.246*247
When (334;
R' = R2 = H) is irradiated (A = 250 nm), at 8 K, in an argon or nitrogen matrix,
the thiiren (335; R' = R2 = H) is produced. The major i.r. bands of both thiiren
and its mono- and di-deuterio-derivatives have now been characterized. The
photolysis of the trithiocarbonates (336; R = H or CF,) in an argon matrix seems
to be a good source of substituted thiiren~.',~
Flash thermolysis of the thiadiazoles (334; R' = Me, Pr', But, Ph, C1, or CN;
R2 = Me, Pr', But, or Ph) gave the thioketens R'R2C=C=S, which could be
detected spectroscopically.249From irregularities in the migratory aptitudes of R'
it has been suggested that thiirens (335) participate in the formation of the
thioketens.
The addition of (337; X = BF, or BCI,) to (338; Ar = 4-MeOC,H4, R = Me)
in liquid SO2 at -60°C gives (E)-(340) and (E)-(341) via attack on the inter-
mediate thiirenium salt (339) by dimethyl disulphide (Scheme 17).25nProton
+
Me-S-S--Me
I + ArCrCR -+
Me-S X- (338)
(337)
M+e-)
Ar + MeS)+Me
+
Me-S Me Ar S-Me
Me-; X- '- ;-Me
(340) (341)
Scheme 17
244 A. S. Gybin, V. A. Smit, V. S. Bogdanov, and M . Z. Krimer, Izu. Akad. Nauk SSSR,Ser. Khim.,
1979, 1663 (Chem. Abstr., 1979,91, 1 4 0 4 5 8 ) .
245 G . Capozzi, V. Lucchini, and G. Modena, Reu. Chem. Intermed., 1979, 2, 347.
246 A. Krantz and J . Laureni, J. Org. Chem., 1979, 44, 2730.
247 M . Torres, I. Safarik, A. Clement, J. E. Bertie, and 0. P. Strausz, Nouc. J. Chim., 1979, 3, 365.
248 M. Torres, A. Clement, H. E. Gunning, and 0. P. Strausz, N o u n J. Chim., 1979, 3, 149.
24y E. Schaumann, J. Ehlers, and H. Mrotzek, Liebigs Ann. Chem., 1979, 1734.
25" G. Capozzi, L. DaCol, V. Lucchini, G . Modena, and G. Valle, J. Chem. Sac., Perkin Trans. 2, 1980,
68.
n.m.r. studies and studies of the products of this reaction and of the similar
reactions of (338; Ar = Ph, R = Me) and (338; Ar = Ph, R = Et) have led to
the suggestion that these thiirenium salts may have some p -thiovinyl-cation
character, and are perhaps better represented as (342). This would explain their
greater reactivity towards nucleophilic attack as compared with dialkylthiirenium
salts.
7 Diaziridines
A review of three-membered rings with two heteroatoms has been published
which includes diaziridines, diazirines, and o x a z i r i d i n e ~ . ~ ~ '
At 100 "C,under nitrogen, the N-carbamoyldiaziridines (343; R' = Ph, R' =
cyclohexyl or Bun)and (343; R' = 3-C1C6H4or 4-MeOC,H4, R2 = cyclohexyl)
isomerize to (345), which were characterized by 13C n.m.r. and by X-ray
~rystallography.~~'A dipolar intermediate (344) was postulated in the reaction.
The hydrolysis of either (343) or (345) gave acetophenone together with a
substituted semicarbazide.
Ph
-
Mef-NR'
I
CONHR' 0
(343) (344) (345)
The novel rearrangement of (346) to (349) occurs either on heating in toluene

for 2 hours ( 5 5 % ) or with Bu'OK and DMSO at room temperature (85'/0).*'~The
suggested mechanism, involving initial formation of a 1,3-dipolar species (347)
and cyclization to the oxiran (348), is shown in Scheme 18.
@p(-J
\
--+
0 Ho
(346) (347)
HO
1
0.
+--
(349)
Scheme 18
E. Schmitz, Adv. Heterocycl. Chrm., 1979, 24, 6 3 .
252
A. Nabeya, J . Saito, and H . Koyama, J. Org. Chiwi., 1979, 44, 3935.
253 H. W. Heine, L. S. Lehman, A. P. Glaze, and A. W. Douglas, J. Org. Chem., 1980, 45, 1317.
Partial separation of enantiomeric N N ' - dimethyldiaziridines has been achieved

by chromatography on triacetylcellulose.254
8 Diazirines
Diazirines are thermally unstable (often explosive) compounds which decompose
by either one-bond rupture (to intermediate diazo-compounds) or by two-bond
rupture (to carbenes). The decomposition of (350) in the presence of 3-
ClC6H,C0,H gives cis- and trans-(351) and (352).255 The oxidation was shown to
occur after decomposition of the diazirine and thus affords a possible method for
the estimation of the partitioning of the two possible reaction pathways.
(350) (351) (352)
A kinetic study of the thermal decomposition of 3-chloro-3-methoxydiazirine

showed that the reaction was unimolecular both in the gas phase and in solu-
t i ~ n . *A
' ~ direct two-bond cleavage to carbene was suggested for this reaction,
without the formation of a diazo-compound. The authors suggest, however, that
the decomposition of diazirine involves both pathways as competitive processes in
the general case.
The prediction that intramolecular carbene reactions occur more favourably by
singlet than by triplet mechanisms has received support from studies of the
thermolysis and photolysis of (353; R = But or Pr') in Thermolysis or
triplet photosensitization of (353; R = But) yields a mixture of (354; R = Me)
(88-91'/0) and (355; R = Me) (8-12%) whereas direct photolysis and singlet
photosensitization gives the same products but in almost equal amounts.
Thermolysis and triplet excitation of (353; R = Pr') gives (354; R = H) (47-
49%) and (355; R = H ) (SO-Sl"/~) whereas direct photolysis gives these
products in 34-37 and 4 2 4 8 % yields respectively, together with 6-9% of
cis- but-2-ene and 11-13% of trans- but-2-ene. The thermolysis pathway leads
to lowest-energy singlet carbene, which converts into intramolecular products;
the same carbene is obtained by triplet excitation via the lowest-energy triplet
carbene, which spin-inverts. Direct photolysis and singlet excitation generate
electronically excited singlet states or singlet carbenes; these undergo relatively
indiscriminate insertion and rearrangement reactions.
Ph
(353) (354) (355) (356) (357)
254 H. Haekli, M. Mintas, and A. Mannschreck, Chem. Ber., 1979, 112, 2028.
255 M. T. H . Liu and I. Yamamoto, Can. J. Chem.. 1979, 57, 1299.
256 N. P. Smith a n d I. D. R. Stevens, J. Chem. SOC.,Perkin Trans. 2, 1979, 213.
257 K. T. Chang and H. Shechter, J. Am. Chem. Soc., 1979,101, 5082.
Three -Membered Ring Systems 47
The thermal and photochemical reactions of (356; R = But or Ph) with

(Me,Si),Hg or (Me,Ge),Hg gave N-metallated diaziridinyl radicals.258From
irradiation at A 2 400 nm, (356; R = Ph) gave the tetrazinyl radicals (357;
M = Si or Ge), probably through diazirinyl radicals. A theoretical study of the
diazirinyl radical and of the isoelectronic cyanomethyl radical indicates that both
may exist in cyclic and open
The Raman spectrum of difluorodiazirine has been re-examined and a
definitive assignment of all nine vibrational fundamentals of this molecule has
been made.260
9 Oxaziridines
Theoretical ab initio SCF investigations have been reported for the photo-
chemical transformations of oxaziridine into a nitrone, into an amide, or into
me thanal plus nitrene. 261
The cyanonitrones (358; R = H, Me, or Ph) isomerize to the oxaziridines (359)
on irradiation in benzene.262Prolonged irradiation, however, converts (358) or
(359) into (360). A similar reaction of nitrones (361; R' = H, R2 = Me or Pr')
gave (362); on treatment with FeSO,, this eliminated the But group to yield
pyrrolidinones (363).263
R
D IC
0-
(358)
N kb b, '0
(359) (360)
COCN
(362) (363)
The U.V.and c.d. spectra of (364; R = Me, Et, Pr', But, or PhCH,) in EtOH and
in iso-octane have been The chiroptical properties of the oxazir-
idine chromophore were generally characterized by a positive pattern at
190-350 nm. The notable exception to this was a clear negative Cotton effect for
(364; R = Pr'). The seemingly anomalous behaviour of this compound was
interpreted in terms of the possible existence of solvation equilibria and con-
formational rotamers about the N-CHMe2 bond. The relatively new technique
of Liquid-Crystal-Induced Circular Dichroism (LCICD) has been used in the
258 C. Grugel and W. P. Neumann, Liebigs A n n . Chem., 1979, 870.

2s9 Z. Slanina and Z. R. Grabowski, Collect. Czech. Chem. Commun., 1979, 44, 3441.
260 N. C. Craig and M . A. Kliewer, Spectrochim. Acta, Part A, 1979, 35, 895.
261 B. Bigot, D . Roux, A . Sevin, and A. Devaquet, J. A m . Chem. SOC.,1979, 101, 2560.
262 D. St. C. Black, N. A. Blackman, a n d A. B. Boscacci, Aust. J. Chem., 1979, 32,1775.
263 D. S t . C. Black, N. A. Blackman, and L. M. Johnstone, Ausr. J. Chem., 1979, 32, 2041.
264 A. Forni, I. Moretti, G. Torre, and E. Vignudelli, Trfruheciron Lett., 1979, 907.
48 He terocy c 1ic Chem istry
assignment of the absolute configurations of (365; R = 4-BrC6H, or l-naph-

Addition of 2% of chiral material to the achiral nematic liquid crystal
N - (4-methoxybenzylidene)-4'-n-butylaniline(MBBA) generates an induced
c.d. curve, the sign of which can be correlated with the absolute configuration of
the chiral additive. Since the LCICD of four oxaziridines (365; R = Me, Pr',
cyclohex-2-enyl, and PhCH,), of known absolute configuration (2S,3S), cor-
responded to the LCICD of (365; R = 4-BrC6H4or 1-naphthyl) (all negative),
the absolute configurations of the latter compounds were unequivocally assigned
as (2S,3S).
R o
p N
H \
Bu'
(364) (365)
H ,C=CHCH ,N
0
,APh
Ph
H,C=CHCH=NH 'R
(367) (368) (369)
The kinetic resolution of (366) may be achieved by refluxing the enantiomers

with brucine in CH2C12,which leaves an e.e. of (-)-(366). A revised mechanism
for this reaction has been proposed in which the brucine, acting as a base, removes
a proton from the carbon that is a to the nitrogen atom of the oxaziridine ring
and accounts for the formation of EtCH=NH and Pr'CHCOMe during the
reaction.26hThe formation of brucine oxide by transfer of oxygen has been
discounted as a possible reaction pathway. A report of the tertiary-arnine-
catalysed decomposition of oxaziridines bearing a proton on the a -carbon atom,
e.g. (367), ti5 N-unsubstituted aldimines (368) indicates the generality of such
reactions.267New chiral oxidizing agents (369; R = 3- or 4-N0,C6H,) have been
prepared in 68% optical purity.2hXThese compounds have been used in the
asymmetric oxidations of PhSMe, 4-MeC6H4SMe, and PhSBu' (in CHCI,) to
sulphoxides (80-85"/0). The e.e. obtained by this oxidation technique are
1.3-2.0 times better than those obtainable in the same asymmetric oxidations by
using (+)-monoperoxycamphoric acid.
Oxaziridines are attacked by nucleophiles mainly at the nitrogen atom.269The
reactions of amines and sulphides with (370) proceed exclusively via attack at
nitrogen by a concerted SN2-typeprocess, as shown in Scheme 19; thus PhSH and
Me,NH react with (370) to yield PhSNHMe and Me2NNHMe respectively.
265 W. H. Pirkle and P. L. Rinaldi, J. Org. Chem., 1980, 45, 1379.

266 W. H. Rastetter and J . W. Frost, Tetrahedron Lett., 1979, 3353.
267 D. R. Boyd, R. Hamilton, N. T. Thompson, and M. E. Stubbs, Tetrahedron Lett., 1979, 3201.
268 F. A. Davis, R. Jenkins, S. Q. A. Rizvi, and T. W. Panunto, J. Chem. Soc., Chern. Commun., 1979,
600.
"' Y. Hata and M. Watanabe, J. A m . Chem. Soc., 1979, 101, 6671.
Three-Membered R in g Systems 49
PhCHO
+ +
M~-N-Nu
The reactions of (E)-(371)with lithium amide bases, e.g. LiNEt, in THF, give
rise to two products after protonation; i.e., (372) (major) and (373).270It has been
concluded that the reduction product (372) arose primarily by a route involving
electron transfer from the base to (371). The amide product was formed in a
competing isomerization reaction involving simultaneous deprotonation and
ring-opening to the anion of (373).
Ph R'
tP PhCH=NBu' PhCONHBu' hfl-R3
y (372) (373) RZ 0
(374)
But
(371)
Reports have appeared on the mechanisms of hydrolysis of oxaziridines; in

particular, the acid-catalysed hydrolysis of (374; R' = R2 = R3 = Et) appears to
proceed uia concurrent protonation of both the oxygen and the nitrogen atoms of
the ring.271This is consistent with the calculated basicities of oxygen and nitrogen
(which are very similar) but the 0-conjugate acid intermediate is the more
reactive, and undergoes relatively rapid decomposition to Et,CO, MeCHO, and
NH3 by an E 2 process. In a further study, related to the acid hydrolysis of (374;
R', R2, R3 = Me, Et, Bu; Me, Pr', Pr"; H, Ph, Et; H, 4-No2chH4,Et; H, Et, Pr';
and H, 4-N02C6H4, Pr'), the products were again generally derived from
hydrolysis of the 0-conjugate With C-aryl substituents, the hydrolysis of
the N-conjugate acid became more important. It was suggested that steric
inhibition to solvation of the N-conjugate acid provides the rationale for these
results.
270
M. Newcomb and R. A. Reeder, J. Org. Chem., 1980, 45, 1489.
"' A. R. Butler, B. C. Challis, and A . M. Loho, J. Cheni. SOC.,Perkin Truns. 2, 1979, 1035.
272 A. R. Butler, J. G. White, B. C. Challis, and A. M. Lobo, J. Chem. SOC.,Perkin Trcvzs. 2, 1979, 1039.
Four-Membered Ring Systems
BY R. C. STORR
1 Reviews
Reviews on the following aspects of four-membered heterocycles have appeared:
1,2-dioxetans' and the reaction of singlet oxygen with alkenes,2 P-lactam anti-
biotics,' small ring compounds of sulphur and ~ e l e n i u mrecent,~ developments in
, ~ chemistry of benzazetes' and of thiacyclobutenes
the synthesis of a ~ e t i d i n e sthe
(thietes) and their valence tautomers,' and conformational barriers and inter-
conversion pathways in some small ring systems.'
Also of general interest is a discussion of the resonance energies of monocyclic
heteroannulene n-systems containing between three and six atoms and
incorporating four to eight electrons.'
2 Systems containing One Nitrogen Atom

Azetidines and Azetines-Analysis of the cyclobutene S butadiene electrocy-
clic reaction for heteroatom-substituted analogues leads to some interesting
conclusions. Introduction of a heteroatom in place of C-2 does not significantly
affect the nodal pattern of the orbitals, and, as in the all-carbon system, the
disrotatory mode involves crossing of frontier orbitals and should therefore be a
relatively high-energy process. However, a heteroatom in place of C-1 perturbs
the nodal pattern of the frontier orbitals such that in the HOMO it can be shifted
from between C-2 and C-3 to between C-1 and C-2. This leads to a comparable
energy barrier for both rotational modes. Significantly, certain fused azetines d o
open readily by a disrotatory m0de.l'
A number of 1-azetines have been obtained from thermolysis of cyclopropyl
azides, nitriles and alkenes being side products. The cyclopropyl azides were
obtained by transfer of a diazo-group from tosyl azide to cyclopropylamine anions
or from carbene/carbenoid additions to vinyl azides. The azetine (1)was oxidized
' P. D. Bartlett and M. E. Landis, Org. Chem. ( N .Y . ) ,1979, 40 (Singlet Oxygen), p. 243.
* A. A. Frimer, Chem. Rec., 1979,79,359;A . P. Schaap and K. A. Zaklika, Org. Chem. ( N .Y . ) ,1979,
40 (Singlet Oxygen), p. 173.
J . G. Gleason and W. D. Kingsbury, Org Compd. Sulphur, Selenium, Tellurium, 1979, 5,454.
F. A . Davis, Org. Compd. Sulphur, Selenium, Tellurium, 1979, 5 , 187.
N . H. Cromwell and B. Phillips, Chem. Rev.,1979, 79, 331.
' C. W. Rees, Srud. Org. Chem., 1979, 356.
' I).C. Dittmer, Srud. Org. Chern., 1979, 130.
T. B. Malloy, L. E. Baurnan, and L. A. Carreira, Toy. Sfereochern.. 1979, 11, 97.
' W. C. Herndon and C . Parkanyi, Tetrahedron, 1978, 34, 3419.
l o J. P. Snyder, J. Org. Chem., 1980, 45, 1341.
51
52 Hererocyclic Chemistry
by rn-chloroperoxybenzoic acid to the 2,3-dihydroazete N-oxidc (2) and the

oxaziridine (3)." The novel four-membered cyclic nitrone structure, cf. (2),has
previously been claimed in the case of 3,3,4-trimethyldihydroazeteN-oxide,
produced in the base-catalysed cyclizaticrh of the y-tosyloxyket~xime.'~ The first
stable and fully characterized examples of this class of compounds have now been
obtained, together with the expected [2 + 21 adducts, in the reaction of 1-
nitroalkenes with ynamines (Scheme 1). A common zwitterionic intermediate,
which can collapse to [2 + 21 adduct or to dihydroazete N-oxide via a cyclic
nitronate ester, is most probably involved."
0
R3
1
R3
Reagents: i, R3C-CNR;
Scheme 1
Nitrogen analogues ( 5 ) of o-xylylenes are produced as transient intermediates
in the flash pyrolysis of o-amino-benzyl alcohols (4).They do not undergo
ring-closure to benzazetines but cyclize to acridines uia dihydroacridine~.'~
Possibly the same type of imine methide is involved in the thermal and photo-
chemical extrusion of sulphur dioxide from the cyclic sulphones (6),which in this
'
(4)
NPh
H
--+ dFQ2
acH2
case does give the benzazetine.I5
(5)
NPh
Me
(6)R = H or Me
--+
" J . Harnisch and G. Szeimies, Cheni. Ber., 1979, 112, 3914.

l2 D. St. C. Black. R. F. C. Brown, B. T. Dunston, and S. Sternhell, Tetrahedron Lett., 1974, 4283.
" A. D. D e Wit, M. L. M. Pennings, W. P. Trompenaars, D . N . Reinhoudt, S. Harkema, and 0.
Nevestveit, J . Chctn. Soc., Chem. Comtnun., 1979, 993.
l4
Mao and V. Boekelheide, J. Org. Chem., 1980, 45, 1547.
Is M. Lancaster and D. J. H . Smith, J. Chem. Soc., Cham. Commun., 1980, 471.
Fo r- Me m be re ci R in g S y stc tns 53
Other papers of interest in connection with azetidines include further details of

the photochemical formation of azetidine derivatives from 2-cyanopyrroline
N-oxide,I6 syntheses of 2- and 3-pyridylazetidines" (as nicotine analogues), the
photochemical addition of the isoxazoline ( 7 ) to benzene, furan, and thiophen,"
and several examples of [3 + 11 addition of isocyanides to azomethine ylides.l9
( 7 ) Ar = p-CNC6H4
Azetidinones-A considerable number of papers involving 0-lactams have

appeared again this year. Those concerned with 0-lactam antibiotics are not
covered in this review except where interesting aspects of the construction or
transformation of the azetidinone ring are involved.
A convenient synthesis of the 0-Iactam ring by a [3 + 13 cyclization has been
reported2('(Scheme 2). A new approach to 4-benzoylazetidinones involves bond
formation between N-1 and C-4, as shown in Scherr e 3.21Conditions have been
SPh
PhSCH ,
I
OJ-HR 0
Reagents: i, NaH, D M F ; ii, CH21,
Scheme 2
PhCO-C
0,H -+
'
PhCO
LBrC 0 z H -!!+ A r NJcOph
H - 0
Reagents: i, Rr,, Et,O: ii, DCC, ArNH,; iii, Amberlite resin
0
Scheme 3
optimized so as to make the cyclization of P-halogeI o-propionamides an attrac-

tive route to unfused P-lactams.22Further details of the formation of p-lactam
derivatives (8) by irradiation of 4-pyrimidones in alcoholic solution have
a ~ p e a r e d . Hydrolysis
'~ of the p-lactams (8) on alumina gives (9) by C-N bond
cleavage, uia a hemiacetal. In fused systems, e.g. (lo), this hemiacetal inter-
mediate rearranges to give the product (11) that results from intramolecular
migration of an alko~y-group.'~
l6 D. St. C. Black, N. A. Blackman, a n d A . B. Boscacci, Ausrr. 1. CIieni., 1979, 32, 1775.
" H. V. Secor and W. R . Edwards, J. O r g . Chrni., 1979, 44, 3136.
" T. Kamagai, Y. Kawamura, K. Shimizu, and T. Mukai, Korn Yoshishu - Hibenzenkei Hokozoku
Kagaku Toronkai [oyobi] Koro Yirki Kagaku Tnronkui 12th, 1979, 317 (Chem. Ahstr., 1980, 92,
197 557).
l 9 J . Charrier, H . Person, and A. Foucaud, Tetrahedron Lett., 1979, 1381.
2o K. Hirai and Y. Iwano, Tetrahedron Letr., 1979, 2031.
2 1 R . F. Abdulla a n d J . C. Williams, Tetrahedron Lerf., 1980, 21, 997.
2 2 H. H. Wasserman, D. J. Hlasta, A . W. Tremper, and J . S . Wu, Tetrahedron Left., 1979, 549.
'' S. Hirokami, Y. Hirai, M. Nagata, T. Yamazaki, and T . Date, J. O r g . Chem., 1979, 44, 2083.
24 Y. Hirai, S. Hirokami, M. Nagata, M . Morita, and T. Yamazaki, J. O r g . C h ~ r n .1980,
, 45, 936; S.
Hirokami, Y. Hirai, T. Takashi, M. Nagata, and T. Yamazaki, Kokagaku Toronkai Koen Yoshishrc,
1979. 12.
54 He terocy c 1ic Chcmistry
1
0 R'
Q C O 2 M e -
Photocyclization of NN-bisbenzylmethacrylamide ( 12) proceeds by cleavage
of the biradical (13) t o give dimethylketen and the imine, which recombine. A
small amount of (14) results from the reaction of the keten with amine that is
produced by hydrolysis of the imine. With di-isopropylmethacrylamide this
photodealkylation is the major pathway, the alkylimine being less efficient in
[2 + 21 addition t o the keten.*' An unprecedented type I1 conversion is observed
in the selective formation of p-lactams in the solid-state irradiation of N N -
dialkyl-a-oxoamides (15). In solution, other processes complicate the reaction.26
)--
NCH Ph (14)
Ph
25
H . Aoyama, T. Hasegawa, M . Okazaki, a n d Y. Omote, J. Chrm. Soc., Perkin Trans. I , 1979, 263.
26
H. Aoyama, T. Hasegawa, and Y. Omote, J. A m . Chrm. SOC.,1979, 101, 5343.
Four-Membered Ring Systems 55
The a-thioxamides (16) also undergo abstraction of y-H, to give p-lactams, on

irradiation in solution. Thiones, under similar conditions, suffer abstraction of
6-H, and the preferred y-abstraction with the thioamides has tentatively been
attributed to an electron transfer from the amide nitrogen to the excited thio-
carbonyl group preceding the shift of the proton. a-Oxothioamides are inert to
irradiati~n.~~
R COCO( CH R R ~ ) ~
(15)
HO RZ
-
hr R'*R3
0
& - - N C H RR23
S HS M e
II
PhCCON(CHRMe), -+
PhH
~
n: R Me
(16) R = Meor Et 0
The readily available oxazine (17) can be converted, via the diazo-compound
(18), into the hydroxyethyl derivatives (19), as shown in Scheme 4 ; this is a key
intermediate in the synthesis of thienamych2'
(17) (18)
Reagents: i, diketen; ii, TosN,, NEt,; iii, h v ; iv, reduction
Scheme 4
Many examples of the usual route to p-lactams uia imines and acid chlorides,
ketens, or keten equivalents have appeared.29 These include syntheses of 3-
[bis(alkylthio)rnethylenamin0]-2-azetidinones,~~ of spiro-azetidinones and bis-
azetidinones,3' and the use of 1-methyl-2-halogenopyridinium salts to activate
carboxylic acids towards coupling with imines.32 A non-hazardous alternative
route to 3-amido-2-azetidinones, avoiding the use of azidoacetyl chloride,
involves the reaction of Schiff bases with salts of [(a-methyl-P-methoxycar-
bonyl)vinylamino]acetic acid, e.g. (20),in the presence of ethyl chloroformate, as
shown in Scheme 5. 3 3 Formaldimines can be generated from their trimers by
treatment with Lewis acids immediately prior to reaction with acid chlorides, so
allowing the formation of the nocardicin nucleus which is unsubstituted at C-4.34
27 H. Aoyama, S. Suzuki, T. Hasegawa, and Y Omote, J. Chem. Soc., Chem. Commun., 1979, 899.
28
R. J. Ponsford and R. Southgate, J. Chem. Soc., Chem. Commun., 1979, 846.
29
See, for example, K. M. Hassan and F. M. Aka, Indian J. Chem., Sect. B, 1978,16, 1073; R. Zamboni
and G . Just, Can. J. Chem., 1979,57, 1945; T. Kametani, K. Fukumoto, K. Kigasawa, M . Hiiragi, K .
Wakisaka, K. Tanigawa, and H . Sugi, Heterocycles, 1979,12, 741; E. Schaumann, H . Mrotzek, and
F. Assmann, Liebigs Ann. Chem., 1979, 334; M. A . Abou-Gharbia and M. M. JoulliC, Synth.
Commun., 1979,9, 871.
30
D. Hoppe and E. Raude, Liebigs Ann. Chem., 1979, 2076.
31
M. Roth, Helv. Chim. Acta, 1979,62, 1966; K. M. Hassan and Z. H. Khalil, 2.Naturforsch., Teil B,
1979, 34, 621.
32
S. G. Amin, R. D. Glazer, and M. S. Manhas, Synthesis, 1979, 210.
33
A. K. Bose, B. Ram, S. G. Amin, L. Mukkavilli, J. E. Vincent, and M. S. Manhas, Synthesis, 1979,
543; A. K. Bose, M. S. Manhas, S. G. Amin, J. C. Kapur, J. Kreder, L. Mukkavilli, B. Ram, and J. E.
Vincent, Tetrahedron Lett., 1979, 2771; S . D. Sharma, M. Sumita, and P. K . Gupta, ibid., p. 1265.
34
T. Kamiya, T . Oku, 0. Nakaguchi, H. Takeno, and M. Hashimoto, Tetrahedron Lett., 1978, 5119.
Me
M~O,CCH<~
Me
I
MeCOCH2C02Me Me02CCH=C-NHCH2C02K 5
(20) &--NcH,A~
0
Reagents: i , glycine, KOM; ii, CICO,Et, RCH=NCH,Ar
Scheme 5
Hexafluoroacetone azine gives a p-lactam with acetyl chloride and triethylamine,
and not a 'criss-cross' type of [3 + 21 adduct with the keten.35 Detailed
mechanistic studies of the addition of thioketen (21) to imines have been
interpreted in terms of orbital-symmetry-controlled formation of the dipolar
species (22) rather than a classical zwitterionic intermediate.36
MC,C
(21)
U
(22)
The alternative [2 + 21 cycloaddition route to azetidinones, using chloro-
sulphonyl isocyanate and functionalized alkenes, has been further used in
syntheses of P-lactam antibiotic^.^^ Asymmetric induction in the formation of
P-amino-aa-dimethyl-P-phenylpropionic acid has been achieved, using a
Reformatsky reagent and a chiral Schiff base, the reaction proceeding through a
p-lactam intermediate.38
Useful modifications of the p-lactam nucleus reported this year include the use
of buffered TiCl, to reduce the N - 0 bond of N-hydroxy-2-azetidinones under
conditions where a protecting t-butoxycarbonyl group and the base-sensitive
chiral centre at C-3 are ~ n a f f e c t e dThis
. ~ ~ makes possible an efficient synthesis of
P-lactams from substituted serinehydroxamic acids (Scheme 6).'O Phosphine
imines are useful intermediates in the conversion of azido-P-lactams into the
3-acylamino-derivatives, avoiding the generation of free amine." Sulphenimine
derivative^'^ (23) and their selenium analogues43 are readily obtained from
oxidation of sulphenamido- and selenenamido-cephalosporins and -penicillins,
and this allows the stereocontrolled introduction of a methoxy- or an alkyl(or
ary1)thio-group into the 7a/6a-positions, respectively. The related introduction
of a 3a-methoxy-group into a 3-(pheny1acetamido)azetidinoneby the action
35 K. Burger, F. Hein, H. Schickaneder, and J. Firl, Chem.Ztg.. 1979, 103, 20.
36 E. Schaurnann and J. Ehlers, Chem. Ber., 1979,112, 1000.
37 A. J . G. Baxter, K. H. Dickinson, P. M. Roberts,T. C. Srnale, and R. Southgate, J. Chem. Soc., Chem.
Commun., 1979, 236; F. A. Bouffard, D. B. R. Johnston, and B. G . Christensen, 1. Org. Chem.,
1980,45, 1130.
38 M. Furukawa, T. Okawara, Y. Noguchi, and Y. Terawaki, Chem. Pharm. Bull., 1979, 27,2795.
39 P. G . Mattingly and M. J. Miller, J. Org. Chern., 1980, 45, 410.
4" P. G. Mattingly, J. F. Kerwin, and M. J. Miller, J. A m . Chem. SOC.,1979, 101, 3985.
4' M. D. Bachi and J. Vaya, J. Org. Chem., 1979,44,4393.
42 E. M. Gordon, H. W. Chang, C. M. Cimarusti, B. Toeplitz, and J. Z. Gougoutas, J. A m . Chem. Soc.,
1980,102,1690; T. Kobayashi and T. Hiraoka, Chem. Pharm. Bull., 1979,27,2718.
43 T. Kobayashi and T. Hiraoka, Bull. Chem. SOC. Jpn., 1979, 52, 3366.
+NOH
0 0
Reagents: I, RN=C=NR, H,NOCH,Ph: i i , DEAIH,PPh,; iii, H,. Pd/C; iv, TiCI,
Scheme 6
of LiOMe and Bu'OCl has been used in the synthesis of a 7a-methoxy-

~xacephem.~~
Stereoselective synthesis of 6P-al kyl-penicillanates, using reductive removal of
a 6P-isocyano substituent with tributyltin hydride, has been described." Stereo-
control in the formation of 6-hydroxyalkyl p-lactam antibiotics by trans-
metallation between benzyl 6,6-dibromopenicillanate esters and metal alkyls,
Nu
(23)
(24)
and the addition of the resulting 'anion' to aldehydes, depends on the solvent and
the metal cati0n.j' New routes to 4-mercapto-azetidinones from penem deriva-
tives have been described47and direct introduction of a benzyloxy substituent at
the ring junction of fused p-lactams has been achieved, using t-butyl perbenzoate
in the presence of CUCI.~'A new type of annelation of @-lactams has been
reported in the cyclization of (24) with LiNPr', (LDA) and CuI PBu3?
Ketens undergo [2 + 21 addition to the imidoyl azimines (25). Depending on
the substituents R, the adducts (26)give imidazolines, e.g. (27), or triazolines, e.g.
(28), o n heating.50
The high reactivity of the P-lactam ring towards cleavage by nucleophiles
makes them useful synthons for the -C-Ci0)-C-N moiety.s' A nice example
is to be found in a new synthesis of 1,2-butenolides (29),'2 as shown in Scheme 7.
44
S. CJyeo, I. Kikkawa, Y . Hamashima, H . O n a , Y . Nishitani,K. O k a d a , T . Kubota, K. Ishikura, Y. Ide,
K. Nakano, and W. Nagata, J. Am. Chem. Soc.. 1979, 101, 4403.
45
D. I. John, E. J. Thomas, and N. D. Tyrrell, J. Cliern. Soc., Clierri. Cornmiin.. 1979, 345.
46
J. A. Aimetti and M . S. Kellogg, Tetrahcdrorz Lett., 1979, 3805.
47 T . E. Gunda, I. Lakatos, E . R. Farkas, J . C. Jaszberenyi, J. Tamas, and M. Mak, Tetrahedron Len.,
1979,2929.
48 H. Matsumura,T. Yano, M. Ueyama, K. Tori, and W. Nagata,J. Chem. SOC.,Chin. Conim~rn.,1979,
483.
49
F. Di Ninno, E. V. Linek, and R . G. Christensen, J. Am. Chein. Soc., 1979, 101, 2210.
Perkiri Tmns. I, 1Y79, 192.
J . J. Barr and R. C. Storr, J. Chem. SOC.,
5' S. Kano, T . Ebata, and S. Shibuya, Chem. Pharm. Bull., 1979, 21, 2450.
52 S. Kano. T. Ebata, K . Funaki, and S. Shibuya, J. Org. Chern., 1979, 44, 3946.
58 Heterocyclic Chem istry
Me
R‘ R’
5 ; H P h
R’ 1v R 2 J 0
r k p h
(29)
Reagents: i, LDA; ii, Me,SiCI; iii, R’COCH2R’; iv, m-chloroperoxybenzoic acid; v, MeSO,H
Scheme 7
With acid, the P-lactam (30) undergoes cleavage and re-closure to give the
rearranged salt (31),s3 A similar rearrangement occurs with sodium methoxide or
sodium cyanide in methanol. Some EHMO and CNDO calculations of the optical
rotatory properties of p-lactam structures have been r e p ~ r t e d . ’ ~
Insertion of carbon monoxide into 2-bromo-3-aminopropenes,for example
(32), to give a-methylene-P-lactams (33) can be accomplished using Bu3N in
HMPT under an atmosphere of CO (100 “C, 5 atm), with a catalytic amount of
Pd(OAc), and PPh3.”
Irradiation of trans-3-phenylacetamido-4-(pyruvoyloxy)azetidin-2-ones(34)
provides a new route to azetidine-2,4-diones ( 3 5 ) , which makes such systems
(having a 3-arylamino-group) available for the first time.56Formation of azeti-
53 F. Cavagna, A . Linkies, H. Pietsch, and D. Reuschling, Angew. Chern., Znf. Ed. Engl., 1980.19, 129.
54 D. R . Boyd, J. P. Riehl, and F. S. Richardson, Tefrahedron, 1979, 35, 1499.
5s M. Mori, K. Chiba, M. Okita, and Y. Ran, J. C h n . SOC.,Cl7em. Curnrnun., 1979, 698.
56 A. C . Kaura and R . J. Stoodley, J. Chem. SOC.,Chcm. Cornmiin., 1979, 344.
Fo u r-Me m be red R in g S y stent s 59
PhCH ,NHCH ,C=CH ,

I
Br H 2 c ~ ~ H , P h
(32) (33)
H H
PhCH ,CON
R
k
0
(34)
OCOCOMe
+
hv
PhCH,CON
0
E:(35)
PhCOCO
\ NR -+ p h q N R
/
PhCOCO PhCO,
0
(36)
dine-2,4-diones also occurs on irradiation of amide (36)57and of succinimides.s8

Further details of the synthesis of 4-thioxo-2-azetidinones (38) from 4-(2-
methoxycarbonylethylsulphinyl)-2-azetidinones (37) have a ~ p e a r e d . ' ~The
latter can be synthesized or obtained from penicillin sulphoxides.59 Hydrolysis
and alcoholysis of the 4-thioxo-2-azetidinone system occurs selectively at the
carbonyl group, while 1,3-dipoles (ozone and diazoalkanes) and carbenes attack
at the thiocarbonyl group. The reaction with ozone and also with m-chloro-
peroxybenzoic acid provides another route to azetidine-2,4-diones, and that with
diazoalkanes and carbenes leads to aIkenylidene-2-a~etidinones.~~ Examples of
R'
57 H . Aoyama, M. Sakamoto, and Y. Omote, Kokagaku Toronkai Koen Yoshishu, 1979, 18 (Chem.
Abstr., 1980, 92, 197 662).
K . Maruyama, T. Ishitoku, and Y. Kubo, J. A m . Chem. SOC., 1979,101, 3670.
s9 M. D. Bachi, 0. Goldberg, A . Gross, and J . Vaya, J . Org. Chem., 1980, 45, 1477.
6" M. D. Bachi, 0. Goldberg, A . Gross, and J . Vaya, J. Org. Chern., 1980, 45, 1481.
the formation of 2-imidoazetidin-4-ones from ketens and carbodi-imides" and of

the reversible formation of 1,2-diazetidinones from diphenylketen and the
3H-pyrazole (39)h2have appeared.
3 Systems containing Two Nitrogen Atoms or One Nitrogen

and a Second Heteroatom
The addition of diaroyl-diazines to quadricyclane to give the diazetidines (40;
R = COAr) provides a further example of 277- + 2 a + 2 a cycloaddition.63 Of
the four possible modes of cleavage of the diazetidine (40; R = Me), only that
leading to the di-imine (41) is observed on flash pyrolysis. A stepwise pathway,
proceeding through a biradical formed by N-N bond rupture, is considered most
likely.64 Low-temperature irradiation of the pyrazoline (42) gives the bicyclic
diazetine (43). The 4,s -diphenyl analogue, however, gives the cyclopropene uia
the ring-opened diazo-compound, under the same conditions."
Me Me
(42) (43)
The first examples of the 1,3-oxazete system (44) have been prepared by the
sequence shown in Scheme 8.66The first stable 4-imino-1,2-oxazetidines(45)
have been obtained from [3 + 11 cycloaddition of iso.:yanides to N-neopent-
ylidene-t-butylamine N-oxide. Their chemistry is dominated by 0 - N bond
cleavage; for example, acid brings about rearrangement to amino-acid deriva-
tives, and, in the presence of tetrahydroisoquinoline, cyclo-reversion to give
imine and isocyanate can be d e t e ~ t e d . ~
An' unstable 1,3-0xazetidine is involved
in the reaction of the imine (46) with the aldehyde (47) to give the imine (48).68
RCONCS A RCONH-C 4' --+

ii RCO-NySMe
\
X X
(44)
R = Me, Ph, PhCH=CH, or X = NH2, NHMe, NHCH,Ph,
'
Ph, OMe, or SMe

Reagents: i, XH; ii, LiH, Me1
Scheme 8
61 Z . Krawczyk and C. Belzecki, Pol. J. Chem., 1979, 53, 643; E. Schaumann, H. Behr, and G.
Adiwidjaja, Liehigs A n n . Chem., 1979, 1322.
62 R. Huisgen and 13. U. Reissig, J. Chem. SOC.,Chem. Commun., 1979, 568.
6 3 M. E. Landis and J. C. Mitchell, J. Org. Chem., 1979, 44, 2288.
64 M. E. Landis, L. M. Bell, D. C. Madoux, J . C. Mitchell, J . M. Schmidt, and J . A. Spencer, J. A m .
Chem. SOC.,1980, 102, 837.

6 5 W. J. Leigh and D . R. Arnold, Can. J. Chem., 1979, 57, 1186.
" P. Kristian, P. Kutschy, and M. Dzurilla, Collect. Czech. Chem. Commun., 1979, 44, 1324.
67 D. Moderhack and M. Lorke, Angew. Chem., Znt. E d . Engl.. 1980, 19,45.
68 Z. V. Safronova, L. A. Simonyan, Yu. V. Zeifman, and N. P. Gambaryan, Zzo. A k a d . N a u k SSSR,
Ser. Khim., 1979, 1826.
0-
I
Bu‘y =CHBu’
Bu‘N -
qNR BU‘
H‘, H 2 0
MeNH-CHBu‘CONHR + Me,C=O
(45)
The thiazetine (49) is in thermal equilibrium with the ring-opened hetero-

diene ( 5 0 ) ,and on exposure to Sb2Te3at elevated temperature gives the novel
A‘-1,2,4-thiatellurazoline system ( 5 1 y 9 A number of 1,2-thiazetine S-oxides
(52) have been prepared by thermolysis of diazo-ketones in the presence of
N-sulphinyl-amines and from the reaction of 2-acyl-acetamides and thionyl
chloride in the presence of base.” 1,2-Thiazet-2-yls (53),a new class of stable
radicals, are obtained by photolysis and thermolysis of (54) and sulphur amides,
for example (55).71 They are useful as catalysts, regulators, or inhibitors in
radical-initiated reaction^.^^
Ar Ar
F3cp= +
N+Ar F,C ”(
F,C
F3C 0- CF,
F3C
%e~s
(49) (50) (51)
4 Systems containing One Oxygen Atom

0xetans.-Stable oxetens are rare; another example ( 5 6 ) ,this time stabilized by
the ‘perfluoroalkyl effect’, has been r e p ~ r t e d The
. ~ ~ Paterno-Buchi reaction
cannot be used for the synthesis of 2,2-dialkyl-oxetans from aliphatic ketones. A
convenient, one-step conversion of such ketones into oxetans involves use of the
sulphoximide (57) and proceeds via ring-expansion of an epoxide intermediate.74
Unusually high asymmetric induction has been observed in the Paterno-Buchi
reaction of (-)-menthy1 phenylglyoxylate with t e t r a m e t h ~ l e t h y l e n e The
. ~ ~ visi-
69
K. Burger, R. Ottlinger, A . Proksch, and J . Firl, J. Chern. Soc., Cliern. Comrnun., 1979, 80.
’O L. Capuano, G. Urhahn, and A. Willmes, Chern. Ber., 1979, 112, 1012.
” R. Mayer, G. Dornschke, S. Bleisch, and A. Bartl, Tetrahedron Lett., 1978, 4003; R. Mayer, S.
Bleisch, G . Dornschke, A. Tkac, A. Stasko, and A. Bartl, Org. Mugn. Reson., 1979, 12, 532.
72 S. Bleisch, G . Dornschke, and R. Mayer, Ger. (East) P. 138 062.
73 Y. Kobayashi, Y. Hanzawa, W. Miyashita,T. Kashiwagi, T . Nakano, and I. Kurnadaki, J . A m . Chem.
Soc., 1979,101,6445.
74 S. C. Welch and A . S. C. P. Rao, J. A m . Chern. SOC.,1979, 101, 6135.
75 H. Gotthardt and W. Ixnz, A n g e w . ChPm.. Int. Ed. Engl., 1979, 18, 868.
ble-light-induced addition of dienes to 1 -amino-anthraquinones appears to

involve the lowest excited singlet state of the quinone rather than conventional
photoaddition uia the n -+T* triplet.7h Efficient regio- and stereo-selective
formation of oxetans has been observed in the Paterno-Buchi reaction between
styrene or methylstyrene and acetaldehyde. Such additions have been rarely
observed previously, probably because it was thought that transfer of triplet
energy from the carbonyl compound to the styrene, which has a triplet state
of lower energy, would be the exclusive reaction. These additions are likely
to involve the singlet excited aldenyde. Benzaldehyde also reacts, but less
~electively.~'
R
--r
(56) RF = CF3
R'
0
I1 - R2
H,C-S-CH, Na' --+
II
NTos R2 CI c1
Spiro-oxetans (58) are formed as minor products in the decomposition of

. ~ ~ bromonium ion that is
aryldiazomethanes in the presence of p - ~ h l o r a n i l The
derived from (59) suffers intramolecular attack by the hydroxy-group by a
4-exo-tet. rather than a 5-endo-tet. pathway, to give the oxetan (60). This
undergoes stereospecific dehydration to (6 1).79
SiMe,
H--LB~
CH,CH=CHSiMe, 3
THF
Dimethylsilylene inserts into the strained C-0 bond of oxetans, but there is no
apparent reaction with unstrained ethers8" The ring-opening of epoxides and
oxetan with Grignard reagents can be usefully catalysed with copper iodide.81A
novel ring-expansion or -fragmentation occurs when the oxetans (62) are treated
with Lewis acids. Pathway ( a )is favoured by electron-donating substituents in Ar
and pathway ( h )by electron-withdrawing substituents, which favour the forma-
tion of the alternative secondary alkylcarbenium ion.82 The isomerization of
76 H. Inoue. A. Ezaki, H. Tomono, and M. Hida, J. Chem. Soc., Chem. Commun., 1979, 860.
77 H. A. J. Carless, A. K. Mitra, and H. S. Trivedi, J. Chem. SOC.,Chem. Commun., 1979, 984.
78 T. Oshima and T. Nagai, Tetrahedron Lett., 1979, 2789.
79
E . Ehlinger and P. D. Magnus, J. Chem. SOC.,Chem. Commun., 1979, 421.
T.-Y. Yang Gu and W. P. Weber, J. A m . Chem. Sac., 1980,102,1641.
C. Huynh, F. Derguini-Boumechal, and G . Linstrumelle, Tetrahedron Lett., 1979, 1503.
82 H . A. J . Carless and H . S. Trivedi, J. Chern. Soc., Chem. Commun., 1979, 382.
2,2,4,4-tetramethyloxetan to neopentyl methyl ketone with Pt, Rh, and Pd

involves the first such 1,3-shift of a bond to be observed on a noble Protic
acids cause the 2,7-dioxabicyclo[3,2.0]hept-3-enes( 6 3 ) to isomerize to furans
(64), whereas Lewis acids give the isomeric products (65). The former process is
thought to be concerted and the latter to involve a cationic intermediate which
undergoes dissociation and recombination.8" Other investigations of ring-open-
ing reactions of oxetans,*' the synthesis of *H- and '-'C-labelled 2-phenyl-
oxetan," and spectral studies of oxetans and thietansR7have also appeared.
CHC0,R
9
(64)
QH H
CHC0,R
I
OA I
QCHC0,R
2-Oxetanones (P-Lactones).-Electronic effects in the thermal decarboxylation

of 3- and 4-aryl-2-oxetanones indicate that the reaction is concerted but proceeds
through a polar transition state.*' Thermal decarboxylation of @-lactones is the
key step in a convenient synthesis of benzyl en01 ethers from a-benzyloxyacetic
acids (Scheme 9)" and also in the formation of (E)-1-halogeno-1-cyano-2-aryl-
ethenes from halogeno-cyanoketens and aryl aldehyde^.^')
M. Bartok, J. Chem. Soc., Chcm. Cornmun., 1979, 139.
84 S. Jarasz and A. Zamojski, J. Org. Chem., 1979, 44, 3720.
85
N. Watanabe, S. Uemura, and M. Okano, Bull. Chem. Soc. Jpn., 1979, 52, 3611; A. Balsamo, C.
Battistini, P. Crotti, and F. Macchia, Gazz. Chim. Ztal., 1978, 100, 619.
86 C. Schaal and M. Ricard, J. Labelled Compd. Radiopharm., 1979,16,727.
*' J. A. Duckett,T. L. Smithson, and H. Wieser, J. Mol. Struct., 1979,56, 157; J. Jokisaari, K. Raisanen,
and E. Rahkamaa, Rep.-Univ. Oulu, Dep. Phys., 1977, 58, 12 (Chrm. Absrr., 1979, 91, 73 840).
" T. Imai and S. Nishida, J. Org. Chrm., 1979, 44, 3574.
" W. Adam and L. A. A . Encarnacion, Synthesiy, 1979, 388.
90 H. W. Moore, F. Mercer, D. Kunert, and P. Alhaugh, J. A m . Chem. SOC.,1979, 101, 5435.
I . I1 111 I lV PhCH,O R'

PhCH,OCH,CO,H + PhCH20CHC02H
R\L H
M R2
Reagents: i , I D A , at - 78 "C; ii, R'COR'; iii, PhSO,CI, py, at 0-10 "C; iv, SO,, at 30 "C; v, PhSO,CI,
py, at 50-53 "C
Scheme 9
Treatment of the P-lactones (66) with MgBrz in ether at room temperature

brings about quantitative, stereospecific conversion into y-lactones by a novel
dyotropic Wagner-Meerwein rearrangement; this is a reaction of considerable
synthetic ~ o t e n t i a l . ~
A' number of additions (e.g. of nitrenes, carbenes, and
diazo-compounds) to diketen to give spiro-P-lactones, which can be further
transformed, have been For example, photolysis of acyl azides in
the presence of diketen leads to pyrrolinone derivatives (67), presumably as
shown.92With phenyl(trichloromethyl)mercury,the spiro-lactone (68), in which
c1
0 Go
HO
R
0 A0
-
R'scH2n0(69)
0 R~OH
R'SCH2CH=CHC02R2
the four-membered ring can be selectively cleaved, is p r o d u ~ e d . ' The

~ acid-
catalysed addition of alkanethiols to diketen is anti-Markovnikov, and gives
adducts (69) which can be converted in situ into y-substituted crotonic esters by
addition of an alcohol and raising the temperature. In contrast, the acid-catalysed
addition of benzenethiol is Markovnikov, and leads to P-phenylthiocrotonic
acid.9s
Photoaddition of p-benzoquinone to unsymmetrical keten dimers gives the
spiro-adduct (70) together with (71) and (72), which are thought to arise by
" J . Mulzer and G . Bruentrup, Angew. Chem., Znt. Ed. Engl., 1979, 18, 793.
y2 T. Kato, Y. Suzuki, and M. Sato, Chem. Pharm. Bull., 1979, 27, 1181.
93 T. Kato, N . Katagiri, and R. Sato, Chem. Pharm. Bull., 1979, 27, 1176; T. Kato, N . Katagiri, and R .
Sato, J. Chrrn. SOC.,Perkin Trans. 1, 1979, 5 2 5 .
94 T. Kato, T. Chiba, R. Sato, and Y. Yashima, J . Org. Chrm., 1980, 45, 2020.
y5 17. Hertenstein, Angew. Chem., Znt. Ed. Engl., 1980, 19, 127.
(73)
photodecomposition of the regioisorneric spiro-adduct (73),9hpossibly as shown.
Extensive studies of the photoaddition of benzoquinones to allenes, ketens, and
ketenirnines and of the spiro-adducts produced have also a p ~ e a r e d . ~For ~*~*
example, with ketenirnines, irnino-oxirans (74) are the primary adducts, but these
photorearrange to spiro-P-lactarns (75). With Lewis acids, these further iso-
oa
merize as shown.'*
0R +
0
>C=NPh
0 I."qN R R R
R (74) (75)
1 1
Trimethylsilylketen and bis(trifluoromethy1)keten give the methylene-p-

lactone (76)at -78 "C, but this rearranges to the isomeric compound (77) at room
temperature ," Solid 4-diazo- 1-phenyl-5,6-dioxo-1,4,5,6-tetrahydropyridazine
9h K. Ogino, T. Matsumoto, T. Kawai, and S . Kozuka, J. Chem. Soc., Chern. Cornmun., 1979, 644.
97 K. Ogino, T. Matsumoto, and S . Kozuka, J . Chem. Soc., Chem. Cornmun., 1979,643; K. Ogino, K.
Yoshida, and S . Kozuka, J. Chem. Soc., Perkin Trans. I, 1979, 1176; K. Ogino, T. Matsumoto, T.
Kawai, and S. Kozuka, J. Org. Chem., 1979, 44, 3352.
'* K. Ogino, S. Yamashirna, T. Matsurnoto, and S. Kozuka, J. Chem. Soc., Perkin Trans. 1, 1979, 1552.
99 L. I. Livantsova, G. S. Zaitseva, R. A. Bekker, Yu. A. Raukov, and I. F. Lutsenko, Z h . Ohshch.
Khim., 1980, 50, 475.
(78) is transformed slowly into the p-lactone (79).'00Transesterification in the

normally inert succinylsuccinic esters can be accomplished at elevated tempera-
tures uia the strained lactone (SO).'"' Other papers of interest in the area of
P-lactones include synthesis of the thietanone (81)as an isostere of prostaglandin
further use of bromo-lactones in the stereospecific synthesis of cyclohexene
derivatives, l o 3 further studies on the Tishchenko r e a ~ t i o n , ' "and
~ the formation of
imines (82) from chlorosulphonyl isocyanate and chalcones via decarboxylation
of an unstable oxazetidinone intermediate (83).lo5
0
F,C y J - 0 N*O N
'
Ph Ph
F,C
(76) (79)
go
Ar
C0,Me
O 2 0 NS0,Cl
R0,C OH
OH K
0
5 Systems containing Two Oxygen Atoms

Dioxetans.-There is evidence that the 9,lO-dicyanoanthracene-sensitized
photo-oxygenation of a number of alkenes to give 1,2-dioxetans can involve an
electron-transfer mechanism (Scheme 10) rather than formation and cyclo-
addition of singlet oxygen.'06 Although dioxetans have long been assumed to be
involved in the oxidative ring-cleavage of indoles, they have never been observed
DCA* + )=( -+ DCA; +
DCA; + 0, - DCA + 0,'
+-) + 0,;
(DCA = dicyanoanthracene)
Scheme 10
'"O B. Stanovnik, M. Tisler, J . Bradac, B. Budic, B . Koren, and B. Mozetic-Rescic, Heterocycles, 1979,
12,457.
J. Sinnreich and H. Batzer, Helv. Chim. Acra, 1979, 62, 1682.
'"' M. Klich, L. Taliani, and J . Buendia, Tetrahedron Lett., 1979, 4387.
lo' T. Mah, H. M. Sirat, and E. J . Thomas, J. Chem. Res. ( S ) , 1979, 392.
lo4 Z . Jedlinski and M. Kowalczuk, Synthesis, 1979,900; Bull. Acad. Pol. Sci.,Ser. Sci. Chim., 1979,27,
191.
D. N. Dhar and S. C. Suri, Indian J. Chem., Sect. B,1979, 18, 281.
L. T. Spada and C. S. Foote, J. A m . Chem. SOC.,1980, 102, 391; H. P. Schaap, K. A. Zaklika, B.
Kaskar, and L. W. M . Fung, ibid., p. 389.
directly. This has now been accomplished in the case of the highly hindered
derivative (84).'07 The first bis-dioxetan of its type, i.e. (85),has been prepared by
the Rose-Bengal-sensitized photoaddition of oxygen to p-dioxin. It is unusually
stable, and gives benzoic anhydride quantitatively on thermal decomposition.
The yield of triplet excited anhydride is 22% (QT/QS =: 200), making it the best
chemical source for triplet excited anhydrides. ' O x
Based on the usual biradical model for decomposition of simple dioxetans, (86)
shows unexpected thermal instability when compared with (87). It is possible that
a twisting rather than a stretching mode of 0-0 bond cleavage is important in
biradical formation. Steric interactions in (86) could force the conformation to a
twist boat, and this, coupled with the twisting mode of cleavage, would result in a
lower activation energy.log The first example of formation of a dioxetan from
singlet oxygen and a simple alkene which has sterically accessible and abstractable
hydrogen atoms and which does not have electron-donating groups has been
observed with tram-cyclo-octene."" The dioxetan (88; R' and R2 are aryl)
behaves like a simple alkyl-substituted dioxetan when R' and R' are not easily
oxidized. When R' and R' are easily oxidized, (88) is destabilized, and it gives
excited singlet states in high yield by an intramolecular electron-transfer
mechanism."' A negligible heavy-atom effect on the activation energies for
direct chemiluminescence of (89) supports the postulate of a biradical mechanism
for their thermal decomposition."'
0-0
H Ph 0 Ph
Weak emission of light has been observed in the thermal decomposition of

cis- 1,2- cyclobutylene dinitrite. Since this reaction possibly proceeds through the
same type of biradical as would be involved in stepwise decomposition of
dioxetans, the difference between this case and the decomposition of the analo-
gous dioxetan has been tentatively suggested as support for a concerted
mechanism for the latter. ' I 3 For simple unsymmetrical dioxetans, undergoing
107
I. Saito, S. Matsugo, and T. Matsuura, J. A m . Chrm. SOC.,
1979, 101, 4757.
I ox
W. Adam, C.-C. Cheng, 0. Cueto, I . Erden, and K. Zinner, J. A m . Chem. SOC.,1979,101,4735.
I OY
A. L. Baumstark and C. E . Wilson, Teirahedron Lett., 1979, 2569.
110
Y. Inoue,T. Hakushi, and N. J.Turro, Kokagnku ToronkaiKoen Yoshishu, 1979,150 (Chem.Absrr.,
1980,92, 214 798).
111
K. A. Zaklika, T. Kissel, A. I,. Thayer, P. A. Burns, and A. P. Schaap, Photochem. Photobiol., 1979,
30, 3 5 ; see also H. Nakamura and T. Goto, ibid., p. 27, and T . Wilson, ibid.,p. 177.
112
W. Adam and K. Sakanishi, Photochem. Photobiol., 1979, 30, 45.
113
N . Suzuki, AngrM.. Chem., Int. Ed. Engl., 1979, 18, 787.
cleavage uia a biradical intermediate, the energy partition between dissimilar

triplet carbonyl products follows a Boltzmann distribution, based on the reported
triplet carbonyl energies. It has been suggested that a departure from this type of
behaviour may indicate a change in mechanism.'14 Studies of the reaction of
singlet oxygen with a variety of alkenes and alkadienes and of the chemi-
luminescence spectra of the products have been reported. These include the first
evidence for unsubstituted 1,2-dioxetanone from singlet oxygen and keten. l 1
Full details of a thorough study of the chemiluminescence of dimethyl-
dioxetanone (90) have appeared. Two pathways of decomposition are involved,
the higher-energy one leading to excited acetone, the lower-energy one being a
dark reaction. At 30 "C, formation efficiencies for singlet and triplet acetone are
0.1 and 1.5 '7'0, respectively. Addition of easily oxidized aromatic hydrocarbons
leads to dramatic catalysis of chemiluminescence, the catalytic rate constant and
efficiency depending on the potential of one-electron oxidation of the catalyst. A
chemically initiated electron-exchange mechanism has been postulated (Scheme
11).Il6Essentially the same mechanism has also been proposed by other workers
to account for the chemi-excitation of polycyclic hydrocarbons by a-peroxy-
lactones. ' 1 7
0-0
) ho+A + ,?-I) + [ h,:l
0-0- +.
j,
0' 0..
-+ H;-
0
A
( A = aromatic hydrocarbon) 1
Scheme 11
The first iminodioxetans, (91)"' and (92),*19have been prepared from singlet
oxygen and ketenimines. No direct chemiluminescence is observed with (9l ) ,
although enhanced chemiluminescence is observed in the presence of fluorescers.
Excitation yields are 1000-fold lower than for peroxy-lactones, and chemically
initiated electron-exchange luminescence (CIEEL)does not operate as it does for
the latter.11s Compound (92) is weakly chemiluminescent, with a high cD,/cDs
value, and again shows no CIEEL.' l 9 Thus iminodioxetans resemble dioxetans
rather than peroxy-lactones.
'I4 W. H. Richardson, M. B. Lovett, M. E. Price, and J. H. Anderegg, J. Am. Chem. SOC., 1979,101,
4683.
1 IS
D. J. Bogan, J . L. Durant, R. S. Sheinson, and F. W. Williams, Photochem. Photobiol., 1979, 30, 3 .
'Ih S. P. Schmidt and (3. B. Schuster, J. A m . Chem. SOC.,1980, 102, 306.
I" W. Adam and C. Cueto, J. A m . Chem. SOC.,1979, 101,6511.
11u
W. Adam, 0. DeLucchi, H. Quast, R. Recktenwald, and F. Yany, A n g e w . Chem., Znt. Ed. Engl.,
1979, 18, 788.
'"' Y. Ito, T. Matsuura, and H. Kondo, J. A m . Chrm. Soc., 1979, 101, 7105.
6 Systems containing Sulphur

The sulphur-bridged naphthalene (93) has been prepared by photolysis and
thermolysis of naphtho[l,8-&]1,2,3-thiadiazine (94). The presumed inter-
mediate (95) can be intercepted by CS, to give (96), which is also formed in low
yield when (93) is heated or irradiated in CS,. Oxidation of thiadiazine (94) with
peracid gives the mono-S-oxide of (93) by spontaneous extrusion of nitrogen
from the thiadiazine S-oxide.'*'
S
Conformational studies of 3-substituted thietan 1-oxides, using lanthanide

shift reagents, indicate that the (complexed) oxygen atom strongly prefers to be
equatorial.12' Higher optical induction is observed in the photoaddition of
(-)-3-menthyl methacrylate to xanthione for triplet than for singlet excitation.
Possibly rotation in a biradical intermediate allows closure to the thietan to occur
preferentially by the lowest energy pathway, making it more selective than the
concerted singlet addition.'22Fragmei itation of spiro-thietans (97) and (98) can
be induced by visible light, with 2-thioparabonate as the triplet sensitizer.123
The thiazolium salts (99; R = Me or PhCH2) undergo ring-opening and
-contraction to the methylenethietans (100) on treatment with aqueous base.'24
Electrochemical reduction of (101) gives the radical anion of the isomeric
compound ( 102).12'
Me
R'
(98) R' R2
(97) Ph OEt S
1"
Me OEt $R
Me Ph
Me C02Me R
S R R
(101) (102)
Addition of sulphenes to electron-rich alkenes is a well-known route to thietan
dioxides.'26 Iminosulphenes are intermediates in base-promoted reactions of
I2O J . Nakayama, T. Fukushirna, E. Seki, and M. Heshino, J. A m . Chem. Soc., 1979, 101, 7684.
lZ1 D. J. H . Smith, J . D. Finlay, C. R. Hall, and J. J. Uebel, J. Org. Chern., 1979, 44, 4757; see also G.
Fronza, R. Modelli, a n d S. Bradamante, J. Magn. Reson., 1979, 36, 343.
H. Gotthardt and W. Lenz, Tetrahedron Lett., 1979, 2879.
IZ3 H. Gotthardt and S. Nieberl, Liebigs Ann. Chem., 1979, 866.
11. J. Federsel, J . Bergman, and U. Stenhede, Heterocycles, 1979, 12, 7.51.
L. Kistenbruegger, C. P. Klayes, and J. Voss, J. Chem. Rey. ( S ) , 1979, 320.
'26 See, for example; A . G. Shipov, A. V. Kisin,andYu. 1. Raukov,Zh. Ohshch. Khim., 1979,49,1170.
alkanesulphonimidoyl chlorides, and these too can b e intercepted with electron-
rich alkenes. 12' Two new approaches to bis(imino)thietans (104) have appeared.
One involves [ 3 + 11addition of isocyanides to thiiranimines (103), and the other
[2 + 21 addition of a ketenimine to an isothiocyanate. The latter is only successful
with sulphonyl isocyanates; acyl isocyanates act as dienes, to give Diels-Alder
adducts.128Externally stabilized 1,3-dipoIes, for example (lOS), are probably
intermediates in the reversible transfer of sulphur from aryl isothiocyanates to
aryl isocyanides. In the case of arylsulphonyl isothiocyanates and t-butyl iso-
cyanide, these intermediates can be intercepted with a second molecu!e of
isocyanide to give the first tris(imin0)thietans (106).'29
R :C=C=NR,
R:C-S + RZNC +
K
NS0,Ar
R'
NS0,Ar
ArSO,N=C=S
(103) (104)
+
Ru'NC
+
A r S 0 , N =C=S
4
Bu'N=C
y
l S
F= ButN<
NS0,Ar NS0,Ar
(105) (106) NSo2Ar
2,4-Dimethyl-, 2,2,4-trimethyl-, and 2,2,4,4-tetramethyl-3-thietanonescan

be obtained in good yield from the aa'-dibromo-ketones with sodium hydrogen
sulphide. The 'gem effect' is clearly important in this reaction, which fails for less
highly methylated.ketones. This thietanone ring-system undergoes cleavage with
SH- to give a-mercapto-ketones and sulphur as the primary products, via a redox
reaction (Scheme l,).'")
0-
8 S
s, SH
A A
S,
SH
H SH H
+ HSSH
1
s
Scheme 12
Other work on four-membered heterocycles containing one sulphur atom

includes a study of the vacuum-u.v. photodecomposition of thietan l,l-dioxide13*
and the formation of a thietanone from a xanthate and d i ~ h e n y l k e t e n , 'and~~
' ~ ~ is evidence that photolysis of (107) in a matrix at
reports of several t h i e t ~ .There
77 K leads to the o-thiobenzoquinone (108), which is interconvertible with the
'21 C. R. Johnson, E U. Jonsson, and C. C. Bacon, J. Org. Chem., 1979, 44, 2055.
128
G. L'abbe, J. P. Dekerk, J.-P. Declercq, G. Gerrnain, and M. Van Meerssche, Tetrahedron Lett.,
1979,3213.
I29
G. L'abbe. L. Huybrechts, J. P. Declercq, G. Germain, and M. Van Meerssche, J. Chem. SOC.,Chrm.
Commrtn., 1979, 160.
I3O R . Foehiisch and W. Gottstein, Liebigs A n n . Chem., 1979, 1768.
13' A . A . Scala and I. Colon, J . Phys. Chem., 1979, 83, 2 0 2 5 .
13* V . N . Drozd and 0. A. Popova, Zh. Org. Khim., 1979,15,2603.
133 B . H. Patwardhan, E. J . Parker, and D. C. Dittmer, Phosphorrtr Sulfur, 1979, 7,5.
oxathiet (109). On further irradiation, these species lose CO to give cyclo-

pentadienethione (110). The dithio-analogue of (107), on irradiation, also gives
a transient benzodithiet. Monothiobenzil and monothiobipivaloyl do not
appear to photoisomerize to o x a t h i e t ~ . ' ~ ~
s
~ > o + ~ ~ = J - p J : +
(107) ( 1 08) ( 109) (110)
The alkene-1,l -dithiolates (11l ) ,on phosgenation, give labile dithietanones

(112), which give reactions typical of thioketens.'" The structure of the dimer of
the lachrymatory factor (113) of onion has been re-assigned as (114),i.e. the first
stable 1,2-dithietan derivative.13' Procedures for the oxidation of tetrafluoro- and
tetrachloro-l,3-dithietans to the corresponding disulphones have been
developed.137Infrared and Raman spectral studies indicate that 1,3-dithietan is
puckered (C2vsymmetry) when free but planar ( D 2 i Iin) the solid
7 Miscellaneous Four-membered Rings

The stereochemistry of the primary adduct (115) from the ylide (116) and
fluorenone has been determined by X-ray diffraction. The oxygen is apical, and
the blocking of the reorganization of ligands by which it is put in an equatorial
position, as is necessary for breakdown of normal oxaphosphetan intermediates
in the Wittig reaction, accounts for its high ~ t a b i 1 i t y . lOther
~ ~ stable oxaphos-
phetans have been detectedI4' or is01ated.l~' Stable adducts (117), from
azaphospholes (118) and ketones, have been isolated.142
1,4-Di-t-butylsilabenzenehas been generated by base-induced elimination
from 1,4-di-t-butyl-1-chloro-l-silacyclohexa-2,4-diene. It dimerizes to the 1,3-
P. De Mayo, A . C. Weedon, and G . S. K. Wong, J . Org. Chem., 1979,44, 1977.
135 E. Schaurnann and F. F. Grabley, Liebigs A n n . Chem., 1979, 1715.
13' E. Block, A. A . Bazzi, and I,. K. Revelle. J . A m . Cham. Soc., 1980, 102, 2490.
13' R. Seelinger and W. Sunderrneyer, Angew. Chrtn., Int. Ed. Engl., 1980, 19, 203.
V. F. Kalasinsky, E. Block, D. E. Powers, and W. C. Harris, A p p l . Spectrosc., 1979, 33, 361.
H. J . Bestrnann, K. Roth, €2. Wilhelm, R. Roehme, and H. Burzlaff, Angaw. Chem., Itit. Ed. Ens/.,
1979, 18,876.
14" E. Breuer, S. Zbaida, and E. Segall, Tctrclhedron Lett., 1979, 2203.
l4I D. Dakternieks, G. V. Roeschenthaler, K. Sauerhrey, and R. Schnutzler, Cham. Ber.. 1979, 112,
2380.
142 W. S . Sheldrick, D. Schornburg, A. Schrnidpeter, and T. VGn Criegern, Chem. Ber., 1980, 113, 55.
a-
,R4
,OEt
R1\?--6R3
/ \ Ph
Ph Ph C0,Me
( 1 16) ( 1 17)
(1 15)
disilacyclobutane (119) and can be trapped as a [14 + 21 adduct with d i e n e ~ . ~ ~ ~
Pyrolysis of unsubstituted silacyclobutane gives no ~ i l a e t h e n e whereas
'~~ the
1,1,3-trimethyl derivative does give the 1,2-dimethyl~ilaethene.'~~ Structure
(120) has been established for the dimer of silaethene (121).'46 Pyrolysis of
silaphosphetan ( 122) gives products derived from (123).14' Fundamental vibra-
tion frequencies of 1,l -dimethyl- 1-silacyclobutane have been assigned148and the
reaction of the latter with diazoacetic ester has also been Flash
pyrolysis of the selenadiazole (124) gives the selenoketen; this dimerizes, to give
(125), in the condensed p h a ~ e . ' ~ "
B u' 00 I
Bu'
Bu '
OSiMe,
(Me,Si),Si<
OSiMe,
Bu'
Bu'
(119)
14' G. Mark1 and P. Hofmeister, Angrw. Chrm., Int. Ed. Engl., 1979, 18, 789.
144 A. K. Mal'tsev, V. N. Khabashesku, and 0. M. Nefedov, Dnkl. Akad. Nauk SSSR, 1979,247,383.
145 A. K. Mal'tsev, V. N. Khabashesku, and 0.M.Nefedov, Izu. A k a d . Nauk. SSSR, S p y . Khim., 1979,
2152.
'46 A. G . Brook, S. C. Nyburg, W. F. Reynolds, Y. C. Poon, Y . - H . Chang, J.-S. Lee, and J.-P. Picard, J.
A m . Chem. SOC.,1979,101, 6750.
147
C. Couret, J . Escudie, J. Satge, J . D . Andriamizaka, and B. Saint-Roch, J. Organornet. Chern., 1979,
182, 9.
I48
J. R. Durig, D. A. C. Compton, and M. Johnson-Streusand, J. Mol. Struct., 1979, 56, 175.
149 L. P. Danilkina and G. V. Sidorenko, Zh. Ohshch. Khim., 1979, 49, 2776.
A . Holm, C. Berg, C. Bjerre. €3. Bak, and H. Svanholt, J. C/wm. Soc., Chrrn. Cornmun., 1979, 99.
3
Five-Membered Ring Systems ~ ~ ~~~~
BY G . V. BOYD, S. GRONOWITZ & P. A. LOWE
Part I: Thiophens and their Selenium and Tellurium Analogues

by S. Gronowitz
1 General
Two short reviews on the pharmaceutical' and other2 uses of thiophen derivatives
have appeared.
Important progress has been reported on the intramolecular acylation of
long-chain o-(2-thienyl)alkanoic acids. Understanding of the mechanism of
photostimulated and other types of nucleophilic substitution in thiophens is
increasing. In the field of lithium derivatives the so-called tandem-directed
metallation has been used for an elegant synthesis of thiophei; analogues of
anthraquinone and related compounds. A thiophen analogue of saccharine
showed interesting properties as an artificial sweetener. A detailed study of the
reaction of thiophens with various diazoalkanes has been carried out. An
important progress in organic syntheses consists in the use of tetrachlorothiophen
1,l-dioxide and related compounds as reactive cheletropic Diels-Alder reagents.
Compounds such as tetrachloroisotwistenes could be synthesized uia this route.
There is renewed interest in the Birch reduction of thiophen derivatives.
An increased activity in the field of the chemistry of thienothiophens and
thienoisothiazoles can be noticed. Many new complex tricyclic systems have also
been synthesized.
2 Monocyclic Thiophens
Synthesis of Thiophens by Ring-closure Reactions.-The reaction of dipotassium
nitroethylenedithiolate and a-chlorocarbonyl derivatives, followed by oxidation
with iodine, gave ( l).3Treatment of pentane-2,4-dione with carbon disulphide
in the presence of potassium hydroxide, followed by treatment with ethyl
bromoacetate, methyl iodide, and alkali, gave (2).4 Compounds of type (3) were
formed in the reaction of 1-cyanomethylpyridinium chloride with carbon disul-
phide and alkylating agents such as chloroacetonitrile, ethyl bromoacetate,
phenacyl bromide, or chloroacetamide in the presence of alkali, and
intramolecularly cyclized to (4).After S-methylation, the pyridine ring could
be cleaved by reaction with phenylsulphonylacetonitrile and alkali in DMSO
L. S. Fuller, J. W. Pratt, and F. S. Yates, Pharm. Ind., 1979, 41, 979.

* L. S. Fuller, J . W. Pratt, and F. S. Yates, Znf. Chim., 1979, 194, 177.
G. Ronsisvalie, Farmaco, Ed. Sci.,1980, 35, 341.
K. Clarke, W. R. Fox, and R. M. Scrowston, J. Chem. SOC.,Perkin Trans. 1, 1980, 1029.
73
solution to give (5),which, upon treatment with 10% hydrochloric acid, gave the
hydrochioride of the 3,4-diamino-derivative (6).'
A modification of the Fiesselmann synthesis of 3-amino- and 3-hydroxy-
thiophen-2-carboxylates, utilizing the readily accessible 2-chloroacrylonitrile
and methyl 2-chloroacrylate in the base-catalysed reaction with methyl thiogly-
collate, has been described.6 A publication has appeared7describing the synthesis
of thiophen-3-malonic ester from the condensation product of 1,4-dichlorobut-
3-en-2-one and malonic esters through the reaction with sodium sulphide. A
patent describing this reaction was reviewed in the last Report. Thiophen-3-
malonic acid is of pharmaceutical importance as the side-chain intermediate that
is used in the production of the semi-synthetic 0-lactam antibiotic ticarcillin. The
base-catalysed condensation of diketo-sulphides with glyoxal has been used for
the synthesis of 2,5-diacyl-thiophens under mild conditions. The acyl groups were
aroyl, thenoyl, or pivaloyl.' The base-catalysed rearrangement of 4-thiahepta-
1,6-diyne gave the dimeric derivative (7). On the other hand, the t-butyl-
substituted diyne (8a) gave the monomeric compound (9). The mechanism of the
previously studied base-catalysed rearrangement of (8b) has been modified. It
was found that (8b), upon treatment with potassium t-butoxide in t-butyl alcohol
at 20 "C, gave (13)in 73% yield, indicating the reaction to proceed via (lo)-( 12).
The reaction of (13) with the same base system at 95 "C gave (14) in 95% yield;'
rc;J
this had previously been obtained at 60 OC." The reactions of (8) were compared
(7)
R-,
(8) SaL; R
b;R =Ph
= R
But
BU'
yBU' \-=c=-Ph
Y . Tominaga, H. Fujito, H. Norisue, A. Ushirogochi, Y. Matsuda and G . Kobayashi, J. Pharm. Soc.

Jpn., 1979, 99, 1081.
' P. R. Huddleston and J. M. Barker, Synrh. Commun., 1979, 9, 731.
J. P. Clayton, A. W. Guest, A. W. Taylor, and R. Ramage, J. Chem. Soc., Chem. Cornmun., 1979,
500.
Y . Miyahara, J. Heterocycl. Chem., 1979, 16, 1147.
P. J. Garratt and S. B. Neoh, J. Org. Chem., 1979, 44, 2667.
'' I. Iwai and J. Ide, Chem. Pharm. Bull., 1964, 12, 1094.
Five-Membered Rings: Thiophens and their Se and Te analogues 7s
[W]pJqsQs= Ph Ph Ph
(11) (12) (13) (14)

with those of the corresponding oxygen and nitrogen analogues.9 Optically active
(S)-2-(2-methylbutyl)rhiophen(16) was prepared by the reaction of optically
active (15) with sodium carbonate and P4Slo.However, this method was inferior
to the cross-coupling between 2-methylbutylmagnesium chloride and 2-
chlorothiophen, catalysed by nickel(I1)-phosphine complexes. In order to deter-
mine the optical purity of (16), it was ozonolysed to (S)-3-methylpentanoic
acid.”
*
Et-CHCH ,CO(C€I,),CO,H
I k, S
)CH2-&ICD,H
I
Me Me
(15) (16)
The reaction of vinylacetylene with sodium sulphide and sodium hydrosulphide

in DMSO-sodium or potassium hydroxide and water has been studied in detail.
The products formed were (17), (18), and (19). Conditions for selectively
obtaining (17) or (19) have been worked out, while (18)was only formed in 25‘3’0
yield. Interestingly, thiophen is the main product from the reaction of vinylacetyl-
ene with sulphide ions generated from elemental sulphur. The formation of
thiophen appears not to be caused by oxidation of (19) by elemental sulphur.”,
Synthesis of Thiophens from Other Rings.-The easily available (20) was trans-
formed into the enol acetate (21) by its acid-catalysed reaction with isopropenyl
acetate; (21) was very conveniently aromatized to (22), using sulphuryl
ch10ride.l~Compound (20) was also transformed into the tosylate (23) through
the reaction with tosyl chloride in the presence of N-methylmorpholine. Upon
reaction of (23) with sodium disulphide, (24) was obtained.l4Also, these authors
found sulphuryl chloride to be an excellent aromatizing agent; thus (24) gave ( 2 5 )
in 90% yield. The reaction proceeds via chlorinated species, which spon-
taneously aromatize by loss of hydrogen chloride. Also, 2,3-disubstituted 4,5-
dihydro-thiophens are aromatized by sulphuryl chloride. However, in this case
triethylamine must be used in some cases to complete the elimination of hydrogen
ch10ride.I~The thermal decomposition of 2,5-diaryl-1,4-dithiins leads to (26).
I’ R. Menicagli, C. Botteghi, and M. Marchetti, J. Heterocycl. Chem., 1980, 17, 57.
B. A. Trofimov, S. V. Amosova, G . K. Musorin, D. F. Kushnarev, and G. A. Kalabin, Zh. Org.
Khim., 1979,15, 619.
l3 J. B. Press, C. M. Hofmann, and S. R. Safir, J. Org. Chem., 1979, 44, 3292.
l4 P. A. Rossy, W. Hoffmann, and N. Muller, J. Org. Chem., 1980, 45, 617.
(20) (21) R = AcO

(23) R = TsO
(24) (26)
The formation of this product and some kinetic data were taken as evidence for
valence isomerization of the dithiins.lS The minor product (27) from the methyl-
ation of 3-nitro-2,5-diphenyl-1,4-dithiin appears not to be stable, and it rear-
ranges via (28) and (29) to (30a), which is methylated to give the isolated product
(30b).16" Upon photolysis of cycloalkene-thiadiazoles (31), thiophens (32) are
formed, in yields of 7-3 1'/o , together with 1,4-dithiins, 1,3-dithioles, and
1,2,4,5-tetrathians.16'
Me Me
(30) a; R = SYe (31) n = 4 , 5 , 6 , o r 10 (32)

b; R = -SMe2BF4-
Physical Properties of Monocyclic Thiophens.-The ''C n.m.r. spectra of (7) and
(9) show that annelation by small rings results in an upfield shift of the a-carbon
nuclei. The chemical shifts observed on oxidizing thiophens to thiophen 1,l-
dioxides have been discussed.9 The "C chemical shifts for the 2-thienylcarb-
enium ions have been studied. The unusually high sensitivity of the 5-position
in thiophen was discussed in relation to calculated charges, non-additivity of
substituent chemical shifts in para-disubstituted benzenes, and other experi-
mental probes of charge di~tribution.'~" Electron-nuclear spin-lattice relaxation
times for 13C were determined for thiophen and tetrahydrothiophen in the
presence of gadolinium and nickel ~he1afes.I~' The 13C n.m.r. spectra and the
i.r. stretching frequencies of carbonyl groups have been determined for nine
'' K. Kobayashi, K. Mutai, and H . Kobayashi, Tetrahedron Lett. 1979, 5003.
l6 ( a ) T. E. Young and A. R. Oyler, J. Org. Chem., 1980, 45, 933; ( b ) H. Buhl, U. Timrn, and H .
Meier, Chem. Ber., 1979, 112, 3728.
( a )D. A. Forsyth and G. A. Olah, J. Am. Chem. Soc., 1979,101, 5309; ( b )L. Nordenskiold and
J. Kowalewski, J. Chem. Soc., Dalton Trans., 1980, 363; ( c ) A. PerjCssy, M. Janda, and D. W.
Boykin, J. Org. Chem., 1980, 45, 1366; ( d ) A. Perjessy, P. Temkovitz, and D. W . Boykin, Jr.,
Collect. Czech. Chem. Commun., 1979, 44, 2832.
Fiue-Membered Rings: Thiophens and their Se and Te analogues 77
4-(substituted methyl)-thiophen-2-carboxylicacids and 2-(substituted methyl)-

thiophen-4-carboxylic acids, and different types of correlations were
attempted.’” In a correlation analysis of the wavenumbers of the C=O stretching
frequencies of 145 aromatic @-unsaturated carbonyl derivatives, some thiophen
derivatives were i n c 1 ~ d e d . IProtonation
~~ of 2,2’-bithienyl in superacid media
occurred at the 5-position to give the stable 2-(2’-thienyl)-5-thiopheniumion.
The energy barrier to rotation about the bond connecting the two rings was found
to be AG* = 11.4 kcal mol-’ by dynamic n.m.r. spectroscopy. Substituent effects
on the rate of rotation were correlated by u/ constants with a p value of 4.8.18
In connection with an investigation of 31Pn.m.r. spectra of acylmethylenephos-
phoranes, the chemical shift of the 2-thienyl derivative was compared with those
of the corresponding phenyl, 2-furyl, and 1 -methyl-2-pyrrolyl derivatives.”
Some 13C and “ B n.m.r. data for 2-thienylboron derivatives have been
obtained.” The mass spectral fragmentation of fifteen 1-(5-ethyi-2-thienyl)-l-
thia-alkanes has been investigated.” Substituent effects on the fragmentation
involving the transfer of an oxygen atom from the ortho-nitro-group to the
double-bond in the side-chain of styryl-nitrothiophens have been studied.22
Reduction potentials and e.s.r. spectroscopy of (33) have been and the
lithium 2,5-biscyanomethylene-2,5-dihydrothiophen radical anion has been pre-
pared from (33), and its electrical and complexing properties were compared with
those of its carbon analogue.24aMicro-cells for Raman spectroscopy have been
used to detect 0.2 pg of thiophen per ml of benzene.24b
Electrophilic Substitution Reactions of Monocyclic Thiophens.-The reaction of

thiophen with N-(methylsulphony1)hexafluoroacetoneimine gave (34) in 57%
yield.25 Nitration of 3-(diacetoxymethy1)thiophen with acetyl nitrate or cupric
nitrate in acetic anhydride gave the 5 - and 2-isomers in the ratio 2.3 : 3.0. The
product composition from the nitration of 3-methylthiophen was determined to
be 3-methyl-2-nitrothiophen, 78% ; 3-methyl-4-nitrothiophen, 2.1‘/o ; and 4-
methyl-2-nitrothiophen, 20% .26
Extensive racemization of the original sample of ( S )- 2-methylbutanoic acid as
well as of the (S)-2-(2-methylbutanoyl)thiophenoccurred upon P,O,-catalysed
acylation of thiophen.” 2-Acetamidothiophen was selectively mono- or
l8 D. A . Forsyth and D. E. Vogel, J. Org. Chem., 1979,44, 3917.
l9 J. M. Brittain and R. A . Jones, Tetrahedron, 1979, 35, 1139.
J. D. Odorn, T. F. Moore, R. Goetze, H. Noth, and B. Wrackmeyer, J. Organomet. Chem., 1979,
173, 15.
N . G . Foster, P. Chandrasurin, and R. W. Higgins, Biomed. Mass Spectrom., 1979, 6 , 260.
22 D. V. Rarnana and M. Vairamani, Indian J. Chem., Sect. B., 1979, 17, 369.
23 M. L. Kaplan, R. C. Haddon, F. B. Brarnwell, F. Wudl, J. H. Marshall, D. 0. Cowan, and S.
Gronowitz, J. Phys. Chem., 1980, 84,427.
24 ( a ) B. F. Haley, J. Chem. Soc., Chem. Commun., 1979, 1030; ( b ) A. Chapput, B. Roussel, and J .
Montastier, C.R. Hebd. SeancesAcad. Sci., Ser. C, 1979, 289, 283.
25 G. F. Win, A. F. Kolorniets, and G. A . Sokol’skii, Z h . Org. Khim., 1979, 15, 2220.
26 S. Gronowitz and I . Ander, Chem. Scr., 1980,15, 20.
di-formylated, in high yield, by the appropriate choice of the Vilsmeier formylat-
ing conditions.*’ Thiophen has been acylated by its copper([)-promoted reaction
with selenol esters.28 In the formylation and acetylation of 2,5-bis(methyl-
thio)thiophen, 3,5-bis(methylthio)-2-acyl-thiophenswere obtained, in addition
to the expected 3-acyl-2,5-bis(methylthio)thiophen.They were most probably
formed by acylation of 2,4-bis(methylthio)thiophen; under the reaction condi-
tions, this was formed from the 2,5-isomer by protonation and subsequent
disproportionation. The ratio of the 3- and 2-acyl-substituted compounds was
20: 1 in the formylation and between 100: 1 and 5 : 4 for the acetylation,
depending upon reaction conditions.2YVilsmeier formylation of 2-methoxy-5-
(methy1thio)thiophen gave a mixture of isomeric formyl derivatives in which
2-methoxy-5-(methylthio)thiophen-3-carboxaldehyde predominated.30
Treatment of (35),(36), and (37)with 3% sulphuric acid in acetic acid leads
to the spiro-derivatives (38)-(40) by electrophilic r i n g - c l o ~ u r e On
. ~ ~the
~ ~other
~
hand, ring-closure to thiophenic P-positions, as for (41)or (42), could not be
achieved, since elimination to cyclohexenone derivatives occurred instead . 3 2
ipso-Nitration occurred with 4-nitrothiophen-2-carboxaldehyde,yielding 2,4-
dinitrothiophen and small amounts of 4,5-dinitrothiophen-2-carboxaldehyde.
On the other hand, 5-nitrothiophen-2-carboxaldehyde gave 3J-dinitro-
thiophen-2-carboxaldehyde as the main product and small amounts of 2 , 5 -
dinitr~thiophen,~’ Nitration of (43) occurs in the side-chain, yielding (44).The
(36) a; R = H (37)
b; R = M e
w 0
(39) a; R = H
b; R = Me
*’ 0. Meth-Cohn and B. Narine, Synthesis, 1980, 133.

28 A. P. Kozikowski and A. Ames, J. A m . Chem. SOC., 1980, 102,860.
2y Ya.L. Gol’dfarb, M. A. Kalik, N. A. Shul’ts, and L. I. Belen’kii, Zh. Org. Khim., 1979, 15, 1289.
30 Ya.L. Gol’dfarb, M. A. Kalik, and V. K. Zav’yalova, Zh. Org. Khim.,1979, 15, 1540.
31 S. Gronowitz, L. Svensson, N. Stjernstriim, and S. 0. Ogren, Acra Pharm. Suer., 1979, 16, 365.
32 S. Gronowitz, L. Svensson, M. Herslof, A. Tjornebo, N. Stjernstrom, and S. 0. Ogren, Acia Pharm.
Suec.. 1979, 16, 376.
33 P. Cogolli, F. Maiolo, L. Testaferri, M. Tiecco, and M. Tingoli, J. Heterocycl. Chem., 1979,16, 1495.
Five-Membered Rings: Thiophens and their Se and Te analogues 79
0Q
U
(41)
U
(42)
(43) R
(44)R
=
=
H
NO2
‘R
structure was determined by X-ray analysis.34 A detailed paper on the

intramolecular acylation of long-chain o-(2-thienyl)alkanoic acids at the 5 -
position in acetonitrile solution in the presence of trifluoroacetic anhydride and
catalytic amounts of H 3 P 0 4 has appeared. The ring-sizes of the resulting
(2,5)thiophenophan-l-onesranged from 12 to 21. Reliable rate data and
effective molarities were obtained, for use in structure-reactivity orr relations.^^
This cyclization procedure was used for the preparation of a key intermediate in
a five-step synthesis of d l - m u ~ c o n e . ~ ~
Treatment of (45) with toluene-p-sulphonic acid gave (46), which could be
desulphurized with Raney nickel to (47).37
Nucleophilic Substitution Reactions of Monocyclic Thiophens.-The kinetics of

methoxy- and phenylthio-debromination of 3-bromo-2-nitrothiophen and 3-
bromo-4-methyl-2-nitrothiophenin methanol have been studied. No primary
steric effect was o b s e r ~ e d . ~ ’The reactivities of 2-L-3,5-dinitro-4-
isopropylthiophens (L = Br or S02Ph) with aniline, piperidine, and N-methyl-
aniline have been measured in methanol and compared with those previously
observed for the corresponding 2-L-3,5-dinitrothiophens.
Evidence was obtained for a large kinetic secondary steric effect with the
phenylsulphonyl leaving group.39The reaction of 3-bromo-2-iodothiophen with
sodium methoxide in various solvents, and the same reaction of 4-bromo-2-iodo-
and 4-bromo-3-iodo-thiophen, led to a ‘halogen-dance’, giving the same mixture
of 3-bromothiophen, bromo-iodothiophens, di-iodobromothiophens, and tri-
iodobromothiophens. The reaction of all three isomeric bromo-iodothiophens
34 L. V. Panfilova, M. Yu. Antipin, Yu. D. Churkin, and Yu. T. Struchkov, Khim. Geterotsikl. Soedin.,
1979, 120.
’’ C. Galli, G. Illuminati, and L. Mandolini, J. Org. Chem., 1980, 45, 311.
36 G . Catoni, C. Galli, and L. Mandolini. J. Org. Chem., 1980, 45, 1906.
37 H. Takahata, M. Hara, A . Tomiguchi, T. Yamazaki, and R. N. Castle, J. Heterocycf. Chem., 1980,
17,403.
3R G . Consiglio, D. Spinelli, and R. Noto, J. Chem. Res. (S),1979, 242.
39 C. Arnone, G. Consiglio, S. Gronowitz, B. Maltesson, A.-B. Hornfeldt, R. Noto, and D. Spinelli,
Chem. Scr., 1978-9, 13, 130.
with sodium methoxide in methanol in the presence of cupric oxide gave
4-bromo-2 -meth~xythiophen.~"
The photostimulated reaction of 3-bromothiophen with cyanomethide ion has
been used for the preparation of 3-thienylacetonitrile; 1,2-bis-(3-thienyl)ethane
was found as a b y - p r ~ d u c t . ~Newcombe
' has continued his interesting investiga-
tions on the complex reactions of nitro-thiophens with the 2-nitropropan-2-ide
ion. 4-Nitro-2-thenylidene acetate gave rise to 4-nitrothiophen-2-carboxal-
dehyde, which was converted into the Meisenheimer complex (48). The corres-
ponding deep red hygroscopic tetramethylammonium salt could readily be
isolated, and its 'H and I3C n.m.r. characteristics were determined. Small
amounts of (49), (50),and (51) were also obtained. Mechanistic routes were
~ u g g e s t e dThe
. ~ ~ reaction of 4-nitro-2-thienyl-methyl and -ethyl chlorides and
acetates with lithium 2-nitropropan-2-ide gave excellent yields of 2-(2-methyl-2-
nitropropy1)- and 2-( 1,2-dimethy1-2-nitropropy1)-4-nitrothiophen. These reac-
tions proceeded by an ionic substitution process, involving nucleophilic attack on
the thiophen ring, as indicated in formulae (52)-(56). On the other hand, the
5-nitro-derivatives gave complex mixtures of products, which arise from SRN 1,
SN2,elimination, electron-transfer and radical-coupling processes. For example,
(57)gave (58)-(61) in 35, 17, 12, and 20% yields, re~pectively.~'
CHRX
Me,CNO,
(52) (53) / (54)
-q 1 N
Q L RI
CMe,NO,
- -o'HJQJ-
Me,C
I
NO2
CHR
I
CMe,NO,
(56) (55)
40 S. Gronowitz, A. Hallberg, and C. Glennow, J. Heferocycl. Chem., 1980, 17, 171.

" Ya. L. Gol'dfarb, A. P. Yakubov, and L. 1. Belen'kii, Khim. Geterotsikl. Soedin., 1979, 1044.
42 P. J. Newcombe and R. K . Norris, Ausi. J. Chem., 1979, 32, 1709.
43 P. J. Newcombe and R. K. Norris, Ausf. J. Chem., 1979, 32, 2647.
Five-Membered Rings: Thiophens arid their Se and Te analogues 81
O2N P C H R O2N O2N

/
Me Me Me
(57) R = C1 ( 5 9 ) X = CMe,
( 5 8 ) R = CMe2N02 (60) X = 0 (61)
2-Acetyl-5-bromothiophen reacted with triphenylphosphine in the absence of

solvent, at 200 "C, to give (5-acetyl-2-thienyl)triphenylphosphoniumbromide.
Competing reaction at the oxygen of the acetyl group leads to the formation of
appreciable amounts of triphenylphosphine oxide. The acetyl group underwent
conventional reactions; e.g., bromination of the side-chain and condensation with
p-dime th ylaminobenzalde h yde .44
The copper-promoted reaction of 1-sodio-pyrazole with 2- and 3-
bromothiophen in pyridine gave good yields of 1-(2-thienyl)- and 1-(3-
thieny1)pyra~ole.~~
Organometallic Derivatives of Monocyclic Thiophens.-Increasing use of
thienyl-lithium compounds for the preparation of a variety of thiophen deriva-
tives as well as other classes of compounds can be noted. The reaction of
4-methyl-2-thienyl-lithium with 1,8-dibromo-octane or 1,2-dibromododecane
has been used for the synthesis of long-chain (w-brom~alkyl)thiophens.~~ Other
thienyl-lithium derivatives have been coupled with 2-(2-bromoethyl)dioxolan to
give compounds (62).46Metallation of 2-methoxythiophen with butyl-lithium,
followed by sulphur and methyl iodide, gave 2 -methoxy - 5-(methylthio)thiophen,
which was metallated in the 3-po~ition.~'The reaction of 2,5-di(methyl-
thi~)thiophen,~'as well as of 3,4-dichloro-2,5-di(methylthio)thiophen,47 with
butyl-lithium gave lithium-methylthio exchange. 2,4-Di(methylthio)thiophen
has been metallated in the free a-position, and 2,5-di(methylthio)thiophen-3-
carboxaldehyde has been prepared from (63) by metallation and reaction with
[s$-TH2
vcH2CH2c (62)
/O-TH2
\
0-CH, SMe
(63)
0-CH,
sulphur and methyl iodide.29 Alkyltelluro-thiophens that have ortho-carbonyl

groups have been synthesized in a one-pot procedure from 3-bromothiophen by
halogen-metal exchange with butyl-lithium, followed by DMF or dimethyl-
acetamide, followed by metallation (with butyl-lithium) of the intermediate in
the 2-position, followed by reaction with dimethyl ditelluride. Alternatively,
acetal-protected thiophen-3-carboxaldehydeor 3-acetylthiophen was metallated
44 0 . M. Bukachuk, I. V. Megera, M. I. Porushnik, and M. I. Shevchuk, Zh. Obshch. Khim., 1979,
49, 1552.
45 S . Gronowitz and S. Liljefors, Chem. Scr., 1978-9, 13, 157.
46 C. G. M. Janssen, A. A. Macco, H. M. Buck, and E. F. Godefroi, R e d . Trau. Chim. Pays-Bas [ J .
Roy. Netherlands Chem. SOC.],1979,98, 448.
47 A. Hallberg, T. Frejd, and S. Gronowitz, Chem. Scr., 1978-9, 13, 186.
in the 2-position and converted into the methyl telluroether by reaction with
tellurium and methyl iodide.48 Especially interesting is a comparison of the
reactions of 3-(n-butylseleno)- and 3-(n-butyltelluro)-thiophens;while the for-
mer undergoes metallation in the 2- and 5-positions in the proportion 3 : 2, the
corresponding tellurium compound selectively gave lithium-butyltelluro
exchange, resulting in 3-thienyl-lithium and dibutyl telluride. On the other hand,
L D A caused selective metallation in the 5-position, and, upon reaction with
NN-dimethylacetamide, 2-acetyl-4-butyltellurothiophen was obtained. Using
similar reaction paths as indicated above, compounds of type (64) and (65) have
oTeR1
(64)
'
yjTeR' COR2
R'OC
(65)
c1JMe
(66)
'OMe
been prepared from thienyl-lithium derivative^.^^ 3-Bromo-5-chloro-2-

methoxythiophen and 3-bromo-2-chloro-5-methoxythiophenunderwent halo-
gen-metal exchange at -70 "C to the corresponding lithium compounds,
which were stable at this temperature. A t room temperature, ring-opening
occurred, and upon reaction with dimethyl sulphate, (66) was obtained. This was
also the product when 2-chloro-5-methoxythiophenwas treated with butyl-
lithium and dimethyl sulphate at room t e m ~ e r a t u r e . 3,4-Dichloro-2,5-
~~
dimethoxythiophen gave dibutyl and diphenyl sulphide with butyl- and phenyl-
lithium, respectively; this was interpreted mechanistically as an attack by the
organolithium reagent on the sulphur atom of the thiophen ring.47
A very elegant and convenient synthesis of thiophen analogues of
anthraquinones has been developed by so-called tandem-directed metallation.
Thus (67), obtained by metallation of NN-diethylbenzamide with s-butyl-lithium
in T M E D A at -78 "C, reacted with thiophen-3-carboxaldehydeto give (68); this,
upon subsequent addition of s-butyl-lithium, was metallated in the 2-position of
the thiophen ring, which, upon heating to room temperature, intramolecularly
attacked the amide bond to give Compounds such as (36) and (37) were
prepared by the reaction of the appropriate lithiated thiophen and (70).31*32
Compound (7 1) has been prepared from the corresponding bromo-compound
by halogen-metal exchange." Halogen-metal exchange between 3-bromo-2,3'-
48 N. Deru and J.-L. Piette, Bull. SOC.Chim. Fr., Part 2, 1979, 623.
49 S. Gronowitz, A. Hallberg, and T. Frejd, Chem. Scr., 1980, 1 5 , 1 .
'' M. Watanabe and V. Snieckus, J. A m . Chem. SOC.,1980,132, 1457.
51 S. Gronowitz, L. Svensson, M. Herslof, and 0. Karlsson, Acta Pharm. Surc., 1979, 16, 353.
Five-Membered Rings: Thiophens und their Se and Te analogues 83
0
(70) (71)
dithienylmethane and butyl-lithium, followed by reaction with DMF, has been
used for the synthesis of 2,3'-dithienylmethane-3-~arboxaldehyde.~~
Metallation of 2H-thieno[2,3-b]thiopyran by strong bases under relatively
non-polar conditions proceeded exclusively in the 2-position of the thiophen ring.
In polar media, a 2-proton of the thiopyran ring was removed. Upon reaction
with methyl iodide, (72) and (73) were obtained. Further reaction of (72) with
butyl-lithium in THF-HMPT mixtures or with sodium amide in liquid ammonia
gave (74). Compound (74) shows a very interesting spectrum of reactions with
various base-solvent systems. When treated with potassium amide in liquid
ammonia at -6O"C, followed by methyl iodide, (75) was obtained, which also
was the case when butyl-lithium in THF-HMPT was used. However, when
HMPT was omitted, metallation at the vinylic position occurred, leading to (76).
Furthermore, if metallation of (74) with potassium amide in liquid ammonia was
carried out at -33 "C, followed by methylation at -60 "C, (77) was obtained,
most probably due to metallation in the 3-position of the thiophen ring followed
by ring-opening.5'
"":"o
Me Me
Me
(72)
R1cdR2
( 7 3 ) R' = R2 = H
M e c
(75)
o
MeS
(77)
(74) R' = Me,R2 = H
(76) R' = R2 = Me
Trichloro-2-thienylcopper, prepared from the corresponding Grignard
reagent, was coupled with perfluoro- and perchloro-aryl iodides to give the
perhalogenated p h e n y l t h i ~ p h e n s .Halogen-metal
~~ exchange of perchloro-(2-
phenylthiophen) with butyl-lithium occurs preferentially in the 5-position of the
thiophen ring. Metallic magnesium, on the other hand, reacts preferentially at
the benzene moiety, giving l-(trichloro-2-thienyl)-2,3,5,6-tetrachlorophenyl-
magnesium ~ h l o r i d e . ~ 2-Thienyl-lead
' triacetate reacted with durene in
trifluoroacetatic acid to give 2,5 -di(duryl)thiophen in low yield.56The transition-
metal complex (78) has been Some thienylsilatranes have been
52 N. Aggarwal and D. W . H. MacDowell, Org. Prep. Proced. Znr., 1979, 11, 247.
53 R. Grafing and L. Brandsma, R e d . Trav. Chim. Pays-Bas [J. Roy. Netherlands Chem. Soc.], 1980,
99, 23.
54 M. T. Rahman and H. Gilman, J. Indian Chem. SOC., 1979,56,299.
55 M. T. Rahman and H. Gilman, J. Indian Chem. SOC.,1979, 56,346.
56 H. C. Bell, J . R. Kalman, G . L. May, J. T. Pinhey, and S. Sternhell, Aust. J. Chem., 1979, 32, 1531.
'' F. Y. Petillon, F. Le Floch-Perennou, J . E. Guerchais, and D. W. A. Sharp, J. Organomef. Chem.,
1979,173, 89.
'' E. Lukevits, S. K. Germane, N . P. Erchak, and E. P. Popova, Khiin.-Farm. Z h . , 1978, 12, 67.
E. Lukevits, S. Germane, 0. A . Podova. and N. P. Erchak, Khim.-Farm. Zh., 1979, 13, 5 2 .
Photochemistry of Monocyclic Thiophens.-The effect of light on the formation

of the Grignard reagent from 2-bromothiophen has been investigated6" S-Aryl
esters of 3-bromothiophen-2-carboxylic acid and of thiophen-3-carboxylic acid
gave (79) and (go), respectively, on U.V. irradiation. The corresponding S-pyridyl
esters reacted analogously, to yield thieno-azothiochromones.61U.V.irradiation
of (81)leads to the formation of (82), in addition to 2-chloropyridine-3-carboxal-
dehyde and 3,3-thienyl disulphide.62U.V. irradiation of (83) in benzene leads to
generation of the nitrile isopropylide (84),which reacted in a regiospecific
manner with activated C=C and C=O bonds to give A'-pyrrolines and A3-
oxazolines, respectively.63 0
(79)
0
c-c
I
The Structure and Reactions of Hydroxy-, Mercapto-, and Amino4hiophens.-

4-(2-Furyl)-3-thiolen-2-one has been prepared.64The easily available compound
(22) has been converted into acids, amides, and a hydrazide. Electrophilic
substitution in (22) occurred exclusively in the 5-position. The hydrazide was
converted into 3-amino-4-ethoxythiophen via the acid. Evidence has been
presented that these compounds exist as hydroxy- and/or amino-tautomers.'3
Some 5-phenyl-3-hydroxy-thiophenshave been prepared and their fungicidal
and insecticidal activities e v a l ~ a t e d . ~
The
' cyclization of some 2-allylthiophen-3-
thiols and 3-allylthiophen-2-thiols has been investigated.66 The thio-Claisen
rearrangement of cyclopent-2-enyl 2-thienyl sulphide leads to (85) and (86).67
" B. Gandha and J. K. Sugden, Synth. Commun., 1979,9, 845.
" K. Beelitz, G. Buchholz, and K. Praefcke, Liehigs. Ann., Chem., 1979, 2043.
62 K. Beelitz, K. Praefcke, and S. Gronowitz, Z. Naturforsch., Teil B, 1979, 34, 1573.
6 3 K.-H. Pfoertner and R. Zell, Helv. Chim. Actu, 1980, 63,645.
'4
K. Spirkova, J. KovaE, V. KoneEnL, M. Dandarova, and M. eernayova, Collect. Czech.
Chem. Commun., 1980,45, 142.
65 P. K. Misra, S. C. Misra, R. M. Mohapatra, and A. S. Mittra, J. Indian Chem. SOC., 1979, 56,404.
'' A. V. Anisimov, V. F. Ionova, V. S. Babaitsev, V. K. Govorek, and E. A. Viktorova, Khim.
Geterotsikl. Soedin., 1979, 1062.
'' A. V. Anisimov, V. F. Ionova, V. S. Babaitseev, and E. A. Viktorova, Zh. O r g . Khim., 1979,15,882.
The main products from the co-pyrolysis of thiophen-2-thiol, 2-(methyl-

thio)thiophen, or 2,2'-dithienyl sulphide with tetrafluoroethylene were (87),
together with some (88).6R Thiophen-2-thiol reacted with (4-fluoro-2-iodo-
pheny1)acetic acid to give (89), which cyclized to (90).693-(Acy1amino)thiophens
have been thiocyanated and selenocyanated in the 2-position. These compounds
are easily transformed into thio- or seleno-ethers and -esters by reaction with
sodium sulphide or selenide. The corresponding thiols and selenols could not,
however, be isolated, owing to their rapid oxidation to disulphide and diselenide,
re~pectively.~' However, the salt of 3-aminothiophen-2-thiol was obtained; upon
diazotization, this gave (91),upon reaction with acetic acid and carbon disulphide
it gave (92), and upon reaction with bromoacetic acid followed by acid treatment
it gave (93), which was reduced to the dihydr~thiazine.'~ The disulphide (25) was
oxidized to the sulphonyl chloride, from which, uia the amide, a thiophen
analogue of saccharine (94) was obtained which shows interesting properties as
an artificial ~ w e e t e n e r . ' ~
CO,H
(91) X = N
(89) (90) (92) X = C-SH
(94)
The preparation and formylation of 2-(acetamido)thiophens has been
improved, and high yields have been obtained.27 Many derivatives of (6) have
been prepared, among them bicyclic derivatives such as (95).5 2-Amino-
thiophens have been allowed to react with active-methylene derivatives in the
presence of ethyl orthoformate, to give compounds such as (96)." By allowing
'' A. M. Maksimov, V. E. Platonov, G. G. Yakobson, E. N . Deryagina, and M. G. Voronkov, Zh.
Org. Khim., 1979, 151 1839.
69 M. RajSner, F. MikSik, J. Metyiova, and M. Protiva, Collect. Czech. Chem. Commun., 1979,
44,2997.
70 C. Paulmier, Bull. SOC.Chim. Fr., Part 2, 1979, 592.
71 C . Paulmier, Bull. SOC.Chim. Fr., Part 2, 1980, 151.
72 K. Gewald, H. Schafer, and K . Sattler, Monatsh. Chem., 1979,110, 1189.
ethyl 2-acylamino-5-ethylthiophen-3-carboxylatesto react with the dimer of
y-methoxyphenylthionophosphine sulphide in benzene at 80 "C, (97) was
obtained. In xylene, at 140 "C, (98) was formed.73
Attempts to convert ethyl 2-amino-5-ethylthiophen-3-carboxylateinto the
corresponding bromo-derivative by diazotization followed by Sandmeyer reac-
tion failed. However, reduction of the diazonium salt with hypophosphorous acid
gave ethyl 2-ethylthiophen-4-carboxylate, which was brominated in the 2-
position and which reacted with thiophen-2-thiol in the presence of potassium
carbonate and copper to give (99); this, after hydrolysis, was ring-closed to
(1OO)." Ethyl 2-aminothiophen-3-carboxylateswere also diazotized, and they
reacted with sodium hydrosulphite and aldehydes or ketones to give substituted
t h i e n y l h y d r a ~ o n e sFischer
.~~ indole synthesis, using (lOl), resulted in compounds
(102).75 Starting from 2-amino-3-carbomethoxy-thiophens,(103) has been
~ y n t h e s i z e d .The
~ ~ action of sulphur monochloride on 2-amino-3-carboxy-5-
phenylthiophen or 2-amino-5-phenylthiophenhydrochloride gave (104).77
Z'CbNH2 0
'SMe
S
(95) (97)
E t 02 CN
jc; H N H 2 . HC I
Me R
NCOCH,C,H,OEt - p
(102) X = S o r SO;?
Various Reactions of Monocyclic Thiophens.-In connection with attempts to
obtain a better synthesis of 3-thienylmalonic acid, the reaction of diazoalkanes
with thiophen has been investigated. However, dimethyl diazomalonate gave
the stable ylide (105). Simple diazo-ketones, on the other hand, resulted in
'' K. Clausen and S . - 0 . Lawesson, Nouveau J. Chim., 1980, 4, 43.
74
A . N. Grinev, I. A. Kharizomenova, N . V . Samsonova, and N. M. Kaplina, Khim. Geterotsikl.
Soedin., 1979, 607.
75 L. N. Borisova and T. A . Kartashova, Khim. Geterotsikl. Soedin., 1979, 195.
76 D. Binder, C. R. Noe, and F. Hillebrand, Arch. Pharm. (Weinheim, Ger.), 1979, 312, 845.
77 P. I. Abramenko, T. K . Ponomareva, and G. I. Priklonskikh, Khim. Geterotsikl. Soedin., 1979,477.
substitution in the 2-position, while diazoacetic esters reacted to give cyclopropa-
nation, yielding 2-thiabicyclo[3.1.0]hex-3-ene derivative^.'^ 2-Azidophenyl
3-(2,5-dimethylthienyl) sulphide surprisingly gave 2-methylbenzothiazole on
therm~lysis.~~
The kinetic stoicheiometry and mechanism of action of electrogenerated
bromine with furan, pyrrole, and thiophen have been studied in detail.'" Elec-
trochemical trifluoromethylation of 2,5-dihydrothiophen 1,l-dioxide has been
carried out.81
Reactivities of Side-chains of Monocyclic Thiophens.-The protonation of
various furan- and thiophen-carboxamides in aqueous sulphur acid solution has
been investigated by U.V.spectroscopy. The values of pK,,+ that were calculated
using the H Aacidity function and the Bunnett-Olsen linear free-energy relation-
ship indicate the lower basicity of furan- and thiophen-2-carboxamides with
respect to that of benzamides and of the 3 - d e r i ~ a t i v e sThe
. ~ ~ kinetics of isomeri-
zation of cis-l-(2-thienyl)-2-phenylacrylonitrile,as well as of its 2-fury1 and
2-selenienyl analogues, have been studied in a solution of decahydronapk-
thalene, with methanesulphonic acid and potassium t-butoxide as catalysts, and
the mechanism has been
'Benzylic' Reactivity. 2,5-Dimethyl-3,4-dinitrothiophenhas been condensed
with aromatic aldehydes to give 3,4-dinitr0-2,5-distyryl-thiophens."~An
improved synthesis of 3-nitro-2-styryl-thiophens involves bromination of 3-
methyl-2-nitrothiophen with N-bromosuccinimide, followed by a modified Wit-
tig reaction.85 From 2,5-di(chloromethyl)thiophen, the phosphonate was pre-
pared by the Arbusov reaction, which was used for the preparation of 2,5-
distyryl-thiophens.H6 Trichloromethyl(thieny1)carbinols have been converted
into the corresponding fluoro-derivatives through the reaction with phenyl-
tetrafluoroph~sphorane."~ The liquid-phase catalytic oxidation of phenyl-(2-
thieny1)methane in acetic acid in the presence of cobalt(I1) acetate and sodium
bromide has been investigated.88
Reactions of Thiophen Aldehydes and Ketones.-The synthesis of bis-(4-
methylpent-3-eny1)thiophens was achieved by applying the Wittig reaction to
( 106).46A convenient method for the synthesis of (2-thieny1)ethylene oxide from
thiophen-2-aldehyde and a sulphur ylide has been worked From 2-thenil
and diethyl ketone, (107) was prepared, and its Diels-Alder reactions have been
studied." The reaction of (108) with different Grignard reagents has been
7R R . J. Gillespie and A . E. A . Porter, J. Chem. SOC.,Perkin Trans. 1, 1979, 2624.
19
D. G. Hawkins, 0. Meth-Cohn, and H. Suschitzky, J. Chem. SOC.,Perkin Trans. 1, 1979, 3207.
'"J. Williamson and B. A . W. Coller, Aust. J. Chem., 1979, 32, 2423.
" R. N. Renaud, P. J . Champagne, and M. Savard, Can. J. Chem., 1979,57,2617.
" G . Alberghina, S. Fisichella, and G. Musumarra, J. Chem. SOC., Perkin Trans. 2, 1979, 1700.
83
E. Maccarone, A . Mamo, G. Scarlata, and M. Torre, J. Org. Chem., 1979,44,2896.
84 P. Geetha, K. Rajagopalan, and S. Swaminathan, Indian J. Chem., Sect. B, 1979, 17, 163.
" G. Kumar, K. Rajagopalan, and S. Swaminathan, Indian J. Chem., Sect. B, 1979,18, 541.
" L. Ya. Malkes, R. A. Minakova, and L. V. Kozyreva, Khim. Geterotsikl. Soedin., 1979, 895.
87 A . I. Ayi, R. Condom, T. N . Wade, and R. Guedj, J. Fluorine Chem., 1979,14,437.
M. N. Volkov, 0. A . Kazakova, E. G. Ostapenko, P. A . Konstantinov, and R . I. Shupik, Z h . Org.
Khim., 1979, 15, 1199.
89 J.-P. Maffrand and R. Boigegrain, Heterocycles, 1979, 12, 1479.
yo Y. Yamashita and M. Masumara, Heterocycles, 1980, 14, 29.
studied.” The reaction of pinacoline with 2-acetylthiophen gave 2,2-dimethyl-5-

(2-thienyl)-5 -hydroxyhexan-3-one .92
Further work on the use of the gem-dimorpholine derivative of 2-thienylgly-
oxal for the synthesis of gem-di(acy1amino)- and other derivatives has appeared.93
In connection with work on surfactant complexes of ruthenium, thiophen-2-
aldehydes were condensed with 4,4’-dimethy1-2,2‘-bipyridyl~.~~ From the easily
available 2,3,4-trichlorothiophen,the 5-formyl- and 5-acetyl-derivatives have
been prepared, and from them a large number of derivative^.'^
Reactions of Carboxy- and Cyano-thiophens.-P-Thenoylacrylic acid reacted
with pyrrole to give (109) in good yield.96 The solid-state photo-oligomerization
of the 2-thienylacrylic acid derivative (110)has been i n ~ e s t i g a t e dSome
. ~ ~ amides
between thiophen-2-carboxylic acid and anthranilic acids have been prepared,
in connection with work on their hypoglycaemic activity.”
(110)
Some substituted cyano-thiophens were condensed with acetonitrile to give
the corresponding P-aminothiophen-acrylonitriles,which could be hydrolysed to
the corresponding P-oxothiophen-propionitrile.These compounds showed anti-
inflammatory activity.99
Various Reactions of the Side-chain.-4,5,6,7-Tetrahydrobenzo[b]thien-4-y1-
urea was oxidized to the 7-0x0-derivative by ceric ammonium nitrate; the
91 S. R. Ramadas and N. S. Chandrakumar, Indian J. Chem., Sect. B, 1979,18, 148.
92 V. I. Esafov and V. Ya. Sosnovskikh, Zh. Org. Khim., 1979,15, 1320.
93 Y. Le Floc’h, D. Plusquellec, N. Soyer, and M. Kerfanto, Bull. SOC. Chim. Fr., Part 2, 1979, 409.
O4 0. Johansen, C. Kowala, A. W.-H. Mau, and W. H. F. Sasse, Austr. J . Chem., 1979, 32, 1453.
’’ A. N. Akopyan, S. G. Kon’kova, and A. A. Safaryan, Zh. Org. Khim., 1979, 15, 1045.
96 G. V. Grigoryan and S. G . Agbalyan, Khim. Geterotsikl. Soedin., 1979, 348.
97 J. Bernstein, B. S. Green, and M. Rejto, J. A m . Chem. SOC.,1980,102, 323.
98 H. Asakawa, E. Imamiya, and Y. Hamuro, Chem. Pharm. Bull., 1979,27,1468.
99
D. N. Ridge, J. W. Hanifin, L. A. Harten, B. D. Johnson, J . Menschik, G . Nicolau, A. E. Sloboda,
and D. E. Watts, J. Med. Chem., 1979, 22, 1385.
Five-Membered Rings: Thiophens and their S t and Te analogues 89
7-0x0-derivative showed growth-stimulating properties when fed to animals.'00
New heterocyclic systems have been prepared by treatment of N-benzyl-, N-
thenyl-, or NN-dithenyl-aminoacetaldehyde dimethyl acetals with acid. Thus
(112) was obtained from (111) upon treatment Fiith 6M-HC1. Other isomers
and anisyl analogues were also prepared.l0lUCompound (112) and its analogues
were quaternized and treated with different bases, and their tendencies to
undergo Hofmann elimination or Stevens rearrangement were investigated.
From methylated (112), only (113) was obtained. In other cases, conditions were
found by which one could obtain either type of product, such as (114).101h
(+)-&(2-Thienyl)-P-alanine was obtained by resolving the N-benzyloxycar-

bonyl-DL-amino-acid with quinine and removing the protecting group. Its
absolute configuration was determined by 0.r.d. lo2
Reaction at Sulphur: Thiophen Dioxides.-Treatment of thiophenhydroximine-
dicarboxylic acids (115) with Raney nickel gave 2-amino-octanedioic, 2-
arninodecanedioic, and other aliphatic 2-amino-dicarboxylic acids.lo3
The great usefulness of thiophen 1 , l -dioxides in organic synthesis has recently
been demonstrated. Tetrachlorothiophen 1,l-dioxide was found to be a reactive
cheletropic Diels-Alder reagent. It was found to annelate to a large variety of
olefins, with loss of SO2, to form 1,2,3,4-tetrachlorocyclohexa- 1,3-dienes; these,
upon dehydrochlorination, gave 1,2,4-trichloro-aromatic compounds. Surpris-
ingly, tetrachlorothiophen 1 , l -dioxide reacted with thiophen and gave, after 72 h
at 80 "C, a yield of 61% of the di-adduct (116). 1-Methylpyrrole gave an
. CI C1
100
G . Asato and R. D. Wilbur, Experientia, 1979, 35, 1458.
101
( a ) J.-P. Maffrand, F. Eloy, and M. Lucas, Hererocycles, 1980, 14, 321; ( b )J.-P. Maffrand and M.
Lucas, ibid., p. 325.
102
S. Kuwata, T. Yamada, I. Shinogi, N. Yamagami, F. Kitabashi, T. Miyazawa, and H. Watanabe,
Bull. Chem. SOC.Jpn., 1 9 7 9 , 5 2 , 3326.
103
B. P.Fabrichnyi, I. F. Shalavina, and Ya. L. Gol'dfarb, Z h . O r g . Khim., 1979, 15, 1536.
analogous product, but much more rapidly. Addition of tetrachlorothiophen
dioxide to acyclic 1,5-dienes (which may contain a heteroatom) is a method for
facile synthesis of tetrachloroisotwistenes (117a) and the heteroisotwistenes
(117b) and (117c), respectively. Acyclic 1,6-dienes led to (118). Tetra-
bromothiophen 1 , l -dioxide reacted like the tetrachloro-derivative.lo4 Dichloro-,
tetrachloro-, and tetrabromo-thiophen dioxides reacted with furans in a novel
type of addition-rearrangement reaction to give halogenobenzyl carbonyl com-
pounds. From 3,4-dichlorothiophen 1 , l -dioxide and 2,5 -dimethylfuran, (120)
was obtained, via (119).'05 3,4-Dihydroxy-2,5-diphenylthiophen1,l-dioxide,
which predominantly exists as the tautomer (121a), reacts with primary amines
to give (121b), while (122) is obtained with hydrazines.lo6
Me
(117) a; A = CH2 A
b;A=O (118) A = CH2, 0,or S
C; A = S
X .o
Ph
U P h
I" Ph
, ,J- iO HR
0 2
(121) a; X = OH
b; X = NHR
Di- and Tetra-hydrot hiophens.-Birch reduction of thiophen- 2 -carboxy lic acid

with three equivalents of lithium in liquid ammonia gave 2,5-dihydrothiophen-2-
carboxylic acid and several other products. When the Birch reduction was carried
out with five equivalents of lithium and with methanol as the proton source, a
single product, cis-5-mercaptopent-3-enoic acid, was obtained.'" Birch reduc-
tion of t-butyl5-t-butylthiophen-2-carboxylate gave the 2,5-dihydro-derivative;
upon treatment with zinc dust and trimethylchlorosilane and then quenching
with molar sodium hydroxide, this gave a mixture of (123) and (124) in the
proportions I : 8.'"
An unusually facile Pummerer rearrangement was observed in the conversion
of 4-hydroxy-3-(1-alkylsulphinyl)sulpholans into 4-acetoxy-3-( 1-alkylthio)-2 -
lo4 M. S. Raasch, J. Org. Chem., 1980,45,856.

'"' M. S. Raasch, J. Org. Chem., 1980, 45,867.
lo' W. Ried, 0 . Bellinger, and G. Oremek, Chem. Ber., 1980, 113,750.
'07 W. G. Blenderman, M. M . JoulliC, and G. Preti, Tetrahedron Lett., 1979, 4985.
l o 8 K. Nishino, S. Yano, Y. Kobashi, K . Yamamoto, and I. Murata, J. A m . Chem. SOC.,1979,101,5059.
Five-Membered Rings: Thiophens and their Sr cind Te analogues 91
sulpholens under the influence of excess acetyl chloride at 20 OC.lo9Nitration of

3,4-dimethylthiophen 1,l-dioxide with nitrogen tetroxide led to (125).'"
The base-catalysed isomerization of P-epoxy-sulphones (126) to y-hydroxy-
ap-unsaturated sulphones (127) was shown by kinetic data, an isotope effect, and
stereochemistry to involve an intramolecular suprafacial 1 + 3 hydrogen migra-
tion, with a carbanion-like transition state. l 1' 4-Hydroxy-2-sulpholen, 3-
hydroxy-4-chlorosulpholan,and 3,4-epoxysulpholan were found to react with
thiolates to give mixtures of cis- and trans-3 - hydroxy-4-(alkylthio)sulpholansin
a ratio of 2:3.11*
The reaction of 2-chlorotetrahydrothiophen with phosphorus, carbon, and
nitrogen nucleophiles has provided synthetically useful tetrahydrothiophen
derivatives.' l 3 Decarbethoxylation and ring-opening reactions of 2-tetrahydro-
thienyl-substituted malonic esters has been investigated.' l 4 Photolysis of
pent-4-enyl sulphides led to five- and six-membered non-alkylated heterocycles,
depending on the substituents present,"' and the reaction mechanism has been
investigated.'" The alkenyltetrahydrothiophen (128), with three asymmetric
centres, was generated stereospecifically, by cyclization of the sulphenic acid
derivative (129), for use in macrolide synthesis.' '' Bimolecular substitution at
the benzylic centre in dibenzylsulphonium fluoroborate with thiocyanate anion
was found to be 8000 times faster than the corresponding reaction with (130).
The reason for this was discussed."' The stereochemistry of introduction of
sulphur at C-4 of dethiobiotin in the biosynthesis of biotin has been elucidated.'"
I
OAc
'09 N. N. Novitskaya, B. V. Flekhter, L. V. Spirikhin, and G. A. Tolstikov, Khim. Geterotsikl. Soedin.,

1979, 563.
'lo M. V. Titova, V. M. Berestovitskaya, and V. V. Perekalin, Zh. Org. Khim., 1979, 15, 877.
I" J. Polakova, M. PaleEek, and M. Prochazka, Collect. Czech. Chem. Commun., 1979,44, 3705.
'I2 N. N. Novitskaya, B. V. Flekhter, and G. A. Tolstikov, Khim. Geterotsikl. Saedin., 1979, 1631.
'I3 C. G . Kruse, E. K. Poels, and A. van der Gen, J. Org. Chem., 1979,44, 2911.
'I4 C. G . Kruse, A. C. V. Janse, V. Dert, and A. van der Gen, J. Org. Chem., 1979,44, 2916.
'I5 G. Bastien and J.-M. Surzur, Bull. Sac. Chim. Fr., Part 2, 1979, 601.
'I6 G. Bastien, M. P. Crozet, E. Flesia, and J.-M. Surzur, Bull. SOC.Chim.Fr., Part 2, 1979, 606.
'I7 E. Vedejs and M. J. Mullins, J. Org Chem., 1979, 44, 2947.
'Is J. F. King and G. T. Y. Tsang, J. Chem. SOC.,Chem. C o m m u n . , 1979, 1131.
'I9 D. A. Trainor, R. J. Parry, and A. Gitterman, J . A m . Chem. SOC.,1980, 102, 1467.
Bi- and Poly-heterocycles.-The nitration of 2,2'-bithienyls that contain
electron-donating substituents has been investigated. '21 The electronic structure
and reactivity of (131) have been studied.121 Cyclization of (132) with alcohols
in sodium hydroxide solution led to the formation of (133).'22Cyclization of
the azide derivative (134) gave (135).123Starting from [2-(l-pyrrolyl)-3-
thienyllmethyl isocyanate, the interesting tricyclic system ( 136) has been pre-
pared.1242-(2-Thienyl)-3,4-dicarbethoxyfuran has been prepared from dimethyl
(2-thenoylmethy1)selenoniumbromide and diethyl acetylenedicarboxylate.12s
Nitration, bromination, and metallation of 1-(2-thienyl)- and 1-(3-thienyl)-
pyrazole has been investigated and isomer distributions have been determined.4s
A few iridium complexes of 2-(2-thienyl)pyridine have been prepared, and
characterized by their i.r. and n.m.r. spectra.'26 Electrophilic substitution reac-
tions of 2-(2-thienyl)benzimidazole have been i n v e ~ t i g a t e d . The
' ~ ~ preparation
and some reactions of 5-(2-thienyl)dibenzophospholeand its quaternary salts
have been studied. 12' 2,5-Di-(2-benzoxazolyl)thiophenhas been synthesized.129
0
Naturally Occurring Thiophens.-Re-investigation of the polar fractions of the

aerial parts of Centaurea ruthenica gave, amongst twenty new compounds,
5-hydroxymethyl-2-(3-hydroxypropynyl)thi0phen.'~~ The investigation of two
further Helichrysum species led to the isolation of three new unusual thiophen
derivatives (137)-(139).13' New acetylenic thiophen derivatives such as (140)
have been isolated from Cullumia ~ e t 0 s a . l ~ ~
12" A. V. Yudashkin, A. E. Lipkin, V. P. Zvolinskii, V. F. Zakharov, and V. F. Ignatov, Khim.
'" P. L. Trakhtenberg, M. N. Zernisova, V. F. Zakharov, V. P. Zvolinskii, A. N. Gusarov, and A. E.
Lipkin, Khim. Geterotsikl. Soedin., 1979, 1194.
S . Rault, M. Cugnon de Skvricourt, and M. Robba, Heterocycles, 1979, 12, 1009.
123 S. Rault, M. Cugnon de Stvricourt, and M. Robba, Heterocycles, 1980, 14, 651.
S. Rault, M. Cugnon de Stvricourt, H. El Khashef, and M. Robba, C. R. Hebd. Seances Acad. Sci.,
Ser. C, 1980, 290, 169.
N . N. Magdesieva, L. N . Ngi, and N. M. Koloskova, Zh. Org. Khim., 1979,15, 609.
1 2 6 M. Nonoyarna, Bull. Chem. SOC.Jpn., 1979, 52, 374.
12' M. M. El'chaninov, L. Ya. Oleinikova, and A. M . Sirnonov, Khim. Geterotsikl. Soedin., 1979, 1047.
12' D. W. Allen and B. G. Hutley, Z. Nuturforsch., Teil B,1979, 34, 1116.
'29 Z. Seha and C. D. Weis, Helu. Chim. Acta, 1980, 63, 413.
13" R. Jente, F. Bohlrnann, and S . Schoneweiss, Phytochemistry, 1979, 18, 829.
1 3 ' F. Bohlmann and W.-R. Abraham, Phytochemistry, 1979, 18, 839.
L32 F. Bohlmann and K.-H. Knoll, Phytochemistry, 1979, 18, 1060.
(137) R = C=CH
(138) R = COMe
I I
M e ( C % C ) 2 0 C - - C C H ( O H ) C H ,OMe
(140)
Thiophen Analogues of Steroids.-Thc ketone (141) was condensed with 2-
(carbethoxymethy1)piperidine to give the 10-aza-17-thia-steroid (142).37With
4-0~0-4,5,6,7-tetrahydroben~o[b]thiophenand 2-methyl-3-oxothiophen 1 , l -
s3
dioxide as the precursors of rings A and €3, and D, respectively, (143) was
’ ~ ~ hydrogenation of the 8,14-diene derived from (143) resulted
s y n f h e ~ i z e d ;ionic
in 1,4-addition of h ~ d r 0 g e n . I ~ ~
coo (141) (142)

cflT
(143)
Thiophens of Pharmacological Interest.-Interest in synthesizing tricyclic com-

pounds containing thiophen rings of potential psychopharmacological interest is
continuing. Compounds such as (144),69(145),31and (146)32have been synthe-
sized. Attempts to prepare clothiazepam by the reaction of (147) with
hexamethylenetetramine failed, and gave (148) instead.135
F \ H‘ ”Me,
(145)
(144) C1
52
H NMe2
(147) R
(148) R
=
=
NHCOCH2Cl
133 P. S. Jogdeo and G. V. Bhide, Steroids, 1979, 34, 729. 0

134 P. S. Jogdeo and G. V. Bhide, Steroids, 1980, 35, 133.
13’ Z. Vejdclek, M. Rajiner, E. Svatek, J. Holubek, and M. Protiva, Collect. Czech. Chem. Commun.,
1979,443604.
The syntheses of thieno[3,4-b][l,5]benzoxazepin-l0-one (15l a ) and
thieno[3,4-b][l,5]benzothiazepin-l0-one (15 1b) have been described. The key
step in the synthesis of (15 l a ) was the reaction of 3-ethoxythiophen-4-carbonyl
chloride with o-aminophenol, followed by ring-closure of the amide with PPA.
If pyridine hydrochloride was used in the ring-closure, 3 -(2-benzimidazolyl)-4-
hydroxythiophen was obtained instead. On the other hand, the reaction of
4-ethoxythiophen-3-carbonylchloride with o-aminothiophenol in methylene
chloride plus triethylamine gave the bis-acyl product (149), while 3-(2-
benzothiazolyl)-4-ethoxythiophenwas obtained in benzene as solvent. However,
by allowing 2,2'-dithiobis(aniline) to react with 4-ethoxythiophen-3-carbonyl
chloride, the disulphide (150) was obtained; after reduction with sodium boro-
hydride and reaction with PPA, this gave the desired compound (151b) and
3-(2-benzothiazolyl)-4-ethoxythiophenin equal amounts. Chlorination of (15 1)
' ~ ~ reaction of
with sulphuryl chloride occurred selectively in the 3 - p o ~ i t i o n . The
(152) with chloroacetyl chloride followed by ammonia gave the thienodiazepine
(1S3).I3' The syntheses of thieno[2,3-b]-, thieno[3,4-b]-, and thieno[3,2-b]-
benzothiazines with a (hydroxyethy1)piperazinylpropylside-chain and various
2 -substituents have been described
Dihydrothienocoumarins that have analgesic activity without anti-inflamma-

tory activity have been ~ y n t h e s i z e d . Compounds
'~~ of type (154),with antibac-
terial, antifungal, and other activities, have been ~ynthesized.'~'Some NN'N"-
trisubstituted guanidines that contain thiophen rings and have anti-inflammatory
properties have been ~ y n t h e s i z e d . 'Nitrosation
~~ of methapyrilene in uitro has
been studied."'*
136
J. B. Press, N . H. Eudy, and S. R. Safir, J. Org. Chem., 1980,45, 497.
13' K. Hirai, H. Sugimoto, and T. Ishiba, J. Org. Chem., 1980, 45, 253.
13' C. J. Grol, H. Rollerna, D. Dijkstra, and B. H . C. Westerink, J. Med. Chem., 1980, 23,322.
lJ9 A. Xicluna, H.-E. Ombetta, J. Navarro, J.-F. Robert, and J.-J. Panouse, Chirn. Ther., 1979,14,523.
14" D. R. Shridhar, B. Lal, and N. K. Vaidya, Indian J. Chem., Sect. B, 1979, 18, 251.
14' S. Rachlin, E. Bramm, I. Ahnfelt-Rsnne, and E. Arrigoni-Martelli, J. Med. Chem., 1980, 23, 13.
14' W. J. Mertens, F. M. Vane, S. R. Tannenbaum, L. Green, and P. L. Skipper, J. Pharm. Sci., 1979,
68, 827.
Five-Membered Rings: Thiophens and their Sc und Te amlogires 95
Starting from (155),3-carboxyceph-3-eneshave been prepared.'43 Thiophen-

2 -ace tic acid 44-'46 and thiophen-2-carboxylic derivatives have been used
in work on p-lactam antibiotics.
3 Benzothiophens and their Benzo-fused Systems

Synthesis of Benzo[b]thiophens.-p-Tolyl 2-iodo-4-thienyl ketone was con-
densed with dimethyl succinate and ring-closed to 4-hydroxy-2-iodo-7-( p -
tolyl)benzo[b]thiophen-6-carboxylic acid. 14* The reaction of phenylacetylenesul-
phonamide with sulphur dioxide and hydrogen bromide in ether gave 3-
bromobenzo[b]thiophen-2-sulphonamide.149 The reaction of (156) with active-
methyl derivatives derived from methyl-pyridines, -quinolines, or -isoquinolines
in pyridine gave 3-aminobenzo[b]thiophens (157) with various nitrogen
heterocycles in the 2-po~ition.'~"The product (158), obtained from methyl
thiosalicylate and a-bromoacetophenone, gave (159) upon Dieckmann con-
densation; upon treatment with PPA, (159) was converted into (160)."' Substitu-
tion reactions of 6,7-dihydrobenzo[b]thiophen-4(5H)-onederivatives, as well as
c1- 0
(159) (160) R = H, Me, or Et
143 T. Sugawara, H. Masuya, T. Matsuo, and T. Miki, Chem. Pharm. Bull., 1979, 27, 3095.
144 T. Sugawara, H. Masuya, T. Matsuo, and T. Miki, Chem. Pharm. Bull., 1979,27,2544.
14' Y. Kawano, T. Watanabe, J. Sakai, H. Watanabe, M. Nagano, T. Nishimura, and T. Miyadera,
Chem. Pharm. Bull., 1980, 28,70.
14' T. Tsuji, T. Kataoka, M. Yoshioka, Y. Sendo, Y. Nishitani, S. Hirai, T. Maeda, and W. Nagata,
Tetrahedron Lett., 1979, 2793.
14' M. Shibuya and S.Kubota, Heterocycles, 1979, 12, 1315.
14' H. H. Moussa and B. Haggag, Indian J. Chem., Sect. B, 1980,19, 156.
'49 I. V. Smirnov-Zamkov, Yu. L. Zborovskii, and V. I. Staninets, Zh. Org. Khim., 1979, 15, 1782.
H. Boshagen and W. Geiger, Synthesis, 1979,442.
lS1 K. Gorlitzer and J . Weber, Arch. Pharm. (Weinheim, Ger.), 1980, 313, 27.
their conversion into thieno[2,3-h][ l]benzopyran-8-ones, has been studied."'"
The reaction of [5-methyl-2-(phenylthio)phenyl]acetothiomorpholide with PPA
gave 5-methyl-2-morpholinobenzo[b]thiophen.152b
Physical Properties of Benzothiophens.-The 13C n.m.r. spectra of
benzo[b]thiophens and of benzo[b]thiophen S-oxides and SS-dioxides have been
analysed and the difference in aromaticity in these three classes has been
The absorption spectra of some isomeric bis-2-benzo[b]thiophen-
ethylene indigos have been Such compounds were also obtained
from 3-bromothiochromanones and not, as previously assumed, 3 3'-bisthio-
chromone~.~~~
Substitution Reactions of Benzothiophens.-Friedel-Crafts benzoylation and
acetylation of 3-carbomethoxybenzo[b]thiophen occurred in the 4-and 6-posi-
ti011s.l~~Benzo[b]thiophen underwent facile addition reactions across the 2,3-
bond when treated with aluminium chloride in an appropriate solvent. In carbon
disulphide or dichloromethane it underwent self-addition to give two or
more of the four possible 2- or 3-(2- or 3-benzo[b]thienyl)-2,3-dihydro-
benzo[b]thiophens. In the presence of an aromatic solvent such as toluene,
ethylbenzene, or xylenes at room temperature, solvent addition occurred to give
a mixture of the corresponding 2- and 3-aryl-2,3-dihydrobenzo[b]thiophens.At
80 "C, benzene and toluene gave the fully aromatic 2-aryl-benzo[b]thiophen~.'~~
The anodic oxidation of 4-methoxybenzo[b]thiophen at elevated temperatures
gave benzo[b]thiophen-4,7-quinonebisacetates in excellent yield. lS8 The ring-
closure of 14-(benzo[b]thienyl)tetradecanoic acid with trifluoroacetic anhydride
and H,PO, in acetonitrile has been i n ~ e s t i g a t e d . ~ ~
Reactions of the Side-chain of Benzothiophens.-The 13Cn.m.r. chemical shifts
in 2-benzo[b]thenyl carbenium ions have been in~estigated.'~ The thermal
decomposition of 2-azidophenyl 2-(3-methylbenzo[b]thienyl) sulphide and of
2-azidophenyl 3-(2-methylbenzo[b]thienyl) sulphide proceeded efficiently
through spiro-benzothiazolines to give (161) and (162).795-Hydroxy-3-methyl-
benzo[b]thiophen-2-carboxylic acid is most conveniently decarboxylated by
refluxing with 48% hydrobromic acid.lS9 The decomposition of
benzo[b]thiophen-2(3H)-one and of 3-diazobenzo[b]thiophen-2-one at high
temperatures provided convenient syntheses of benzothiet and the transient
benzothiet keten. The decomposition reactions were carried out in the reactor
of a photoelectron spectrometer.'60Heterotriptycenes have been obtained from
15' ( a )C. M. Asprou, J . S. A. Brunskill, H. Jeffrey, and A. De, J. Heterocycl. Chem., 1980,17, 87; ( b )
V. Valenta, J. Jilek, J. PomykaEek, A. Dlabat, M. Valchai-, J. MetyS, and M. Protiva,
Collect. Czech. Chem. Commun., 1979, 44, 2677.
Is3 P. Geneste, J.-L. Olive, S. N. Ung, M. E. A. El Faghi, J. W. Easton, H. Beierbeck, and J. K.
Saunders, J. Org. Chem., 1979, 44, 2887.
lS4 K. D . Banerji, A . K. D . Mazumdar, and S. K. Guha, J. Indian Chem. SOC.,1979, 55,66.
15' F. Eiden and L. Prielipp, Arch. Pharm. (Weinheim, Ger.) 1980, 313, 31 1.
156
M. Han>oun, N. BlazeviC, D. Kolbah, A. SabljiC, N. TrinajstiC, A . Sega, A. Lisini, F. Kajfei,
and V. SunjiC, J. Heterocycl. Chem., 1979, 16, 1029.
P. D. Clark, K . Clarke, D. F. Ewing, and R. M. Scrowston, J. Chem. SOC.,Perkin Trans. 1,1980,677.
B. L. Chenard and J . S. Swenton, J. Chem. SOC.,Chem. Commun., 1979, 1172.
159 B. D. Jackson and S. B. Bowlus, J. Heterocycl. Chem., 1980,17, 205.
160 R. Schulz and A. Schweig, Tetrahedron Lett., 1980, 21, 343.
the decomposition of 3-diazobenzo[b]thiophen-2-carboxylatesin the presence

of anthracenes. 16'
2-Arylmethylene-5-methylbenzo[b]thiophen-3(2~)-one has been selectively
oxidized by electrophilic reagents at the sulphur atom to give the 1-oxide or
1 , l -dioxide derivatives. Nucleophilic reagents reacted at the olefinic bond, to
give spiro-epoxide derivatives.'62 The previously undescribed system (163) has
been synthesized and its photoinitiated rearrangement to (164) i n v e ~ t i g a t e d . ' ~ ~
2-Formylbenzo[b]thiophen-3-selenoland 3-formylbenzo[b]thiophen-2-selenol
have been prepared uia lithium derivatives, starting from 3-
bromobenzo[b]thiophen or 3-bromo-2-formylbenzo[b]thiophen,'64or, better,
through nucleophilic aromatic substitution of 2-bromo-3-formyl- and of 3-
bromo-2-formyl-benzo[b]thiophenwith selenourea. 165 Derivatives involving the
selenium atom and the formyl group, as well as complexes of bivalent nickel and
copper, were prepared, and tautomerism in the selenolo-aldehydes was
studied
OCOR'
CH=NC6H4R2
N (164)
/ \
R'OC C,H4R2
(163)
The reductive alkylation of 3-aminomethylbenzo[b]thiophenwith formic acid

and formaldehyde, and of 3-(/3-aminoethyl)benzo[b]thiophen with formalde-
hyde and cyanoborohydride, proceeded in good yields.'66Thieno[3,2-f]quinoline
and its 2-carbethoxy derivative have been selectively oxidized with m -chloro-
peroxybenzoic acid to the corresponding N - o x i d e ~ . " ~
Benzo[b]thiophen S-Oxides.-New isoxazolines have been obtained by 1,3-
dipolar cycloaddition of mesitonitrile oxide to the sulphone and sulphoxide of
3 -methylbenzo[b Ithiophen .I6'
Benzo[c]thiophens.-Heating of (165) with sulphur gave ( 166).'69
I6l M. G. Reinecke and H. H. Ballard, Tetrahedron Lett., 1979,4981.

162 L. S. S. Rkarnoan and W. I. O'Sullivan, J. Chem. Soc., Perkin Trans. I , 1980, 1194.
'63 G. D. Palui, A. E. Lyubovskaya, B. Ya. Simkin, V. A. Bren', Yu. A. Zhdanov, M. I. Knyazhanskii,
V. I. Minkin, and L. P. Olekhnovich, Zh. Org. Khim., 1979, 15, 1348.
164 Ya. L. Gol'dfarb, V. P. Litvinov, and V. Yu. Mortikov, Khim. Geterotsikl. Soedin., 1979, 898.
16' V. P. Litvinov, Ya. L. Gol'dfarb, and V. Yu. Mortikov, Khim. Geterotsikl. Soedin., 1979, 905.
166 E. Carnpaigne and E. Homfeld, J. Heterocycl. Chem., 1979, 16, 1321.
167 K. S. Sharma, R. Parshad, and V. Singh, Indian J. Chem., Sect. B, 1979,17, 342.
16' P. Geneste, R. Durand, and D. Pioch, Tetrahedron Lett., 1979, 4845.
16' F. Toda and K. Tanaka, Chem. Lett., 1979, 1451.
Dibenzothi0phens.-The n.m.r. assignment of all carbon nuclei of dibenzo-

thiophen and its S-oxides has been carried out, using deuteriated derivatives
and lanthanide shift reagent^.'^''
Pharmacologically Active Compounds.-Benzo[b]thiophen analogues of
bunitrolol, e.g. 2-cyano-3-(t-butylamino-3-hydroxy-2-propyloxy)benzo-
[blthiophen, that have p- blocking properties have been ~ynthesized.'~'The
antibacterial activities of 2-nitrobenzo[b]thiophens have been compared with
those of 2-nitro-4-0~0-4,5,6,7-tetrahydrobenzo[b]thiophen.'~~ A new oestrogen
antagonist has been found in (167).'73
C,H,OH - p
COC,H,(OCH ,CH ,~3) -p
The pesticide benzo[ blthienyl methylcarbarnate has been derivatized with

methanesulphonyl chloride for g.1.c. analysis.174 Octapeptides into which
henzo[b]thienylalanine has been introduced as a tryptophan congener have been
synthesized.' 7 5
4 Thiophen Analogues of Polycyclic Aromatic Hydrocarbons

Analogues of Anthracene and Phenanthrene.-The tandem-directed metalla-
tion reaction between thiophen-3-aldehyde and thiophen-3-carboxylic acid
diethylamide has been found to be a very useful method for the synthesis of
thiophen analogues of anthraquinones." A detailed procedure for the synthesis
of benzo[l,2-b:4,5-b]dithiophen has been published.52 The reaction of 1-(2-
naphthyl)-5,5-dimethyl-3-oxocyclohexenewith sulphur gave ( 168).17"
Various Carbocyclic Fused Systems.-l,3-diphenyl-4H- 5,6-dihydrocyclo-
penta[c]thiophen-cis-4,6-dicarboxylic acid has been prepared by the reaction of
the appropriate 174-diketo-derivative with phosphorus p e n t a ~ u 1 p h i d e . lThe
~~
reaction of (169) with tolane gave (170).17* Acylation of 2-methoxy-
17" J. Giraud and C. Marzin, Org. Magn. Reson., 1979, 12, 647.
R . Royer, L. Rene, M. Aurousseau, and F. Nicoine, Chim. Ther., 1979, 14,467.
17' J.-P. Bachelet, G . Lamotte, P. Demerseman, R . Royer, and R. Cavier, Chim. Ther., 1979,14, 549.
173 L. J. Black and R. L. Goode, Life Sci., 1980, 26, 14.53.
17' J. C. Maitlen and L. M. McDonough, J. Agric. Food Chem., 1980, 28,78.
175 H. M. Rajh, E. C. M. Mariman, G . I. Tesser, and R. J. F. Nivard, Int. J, Pepr. Protein Res., 1980,
15, 200.
17' D . Nasipuri, A. Sarkar, P. K . Chakraborty, and I. De Dalal, J. Indian Chem. Sac., 1978, 55, 1232.
'77 S. Julia and J. M. Carulla, A n . Quim.,1979, 75, 904.
17' N. E. Kolobova and F. V. Goncharenko, Khim. Geterotsikl. Soedin., 1979, 1461.
Five-Membered Rings: Thiopheris and their Se and Te anrzlogues 99
'U
benzo[b]thiophen with cinnamoyl chloride gave the 3 -cinnamoyl derivative,

which was converted into (171). The chemistry of this phenalene system was
studied in The synthesis of (172) and of its 9,lO-dihydro-derivative, and
their reactions with various organolithium compounds, have been described."
5 Thiophens Fused to Five-membered Heteroaromatic Rings

Thiophen- and Pyrrole-fused Thiophens and Related Compounds.-The reac-
tion of the dithiolate (173) with chloroacetonitrile gave 2,5-dicyano-3-phenyl-4-
methylthien0[2,3-b]thiophen.~~~ An extensive paper describing the synthesis of
thienylthieno[2,3-b]thiophens and bithieno[2,3-b]thiophens, through the reac-
tion of thieno[2,3-b]thienylcopper with iodothiophen and the reaction of
thieno[2,3-b]thienyl-lithium with copper(I1) chloride, respectively, as well as of
the sulphides of these systems (obtained through the reaction of lithium deriva-
tives with thiophen disulphides or other reagents) has appeared.'" Pyrylium- and
pyridine-fused derivatives of thieno[3,2-b]thiophen have been obtained from its
3-acetonyl derivative.18* The complexing properties and nucleophilicities of
some thieno[3,2-c]- 1,2-dithiole-3-thione systems have been investigated.lR3
Some thienopyrroles have been synthesized from nitrostyrylthiophen through
the reaction with triethyl phosphite. H4*85
Pyrazole-, Thiazole-, and Isothiazole-fused Thiophens and Related Systems.-
The synthesis of hitherto inaccessible thienylpyrazolones has been described.lS4
The reaction of (174) with methyl bromoacetate, followed by base-catalysed
cyclization, gave (175). The corresponding thiazole-fused system, on the other
hand, was prepared through the reaction of 2-phenyl-5-chloro-4-formylthiazole
with thioglycollic acid in the presence of sodium methoxide.'*' Another route to
thienothiazoles consists in the reaction of (104) with CS2and sodium hydroxide.77
R. Neidlein and L. Seguil-Camargo, Liebigs Ann. Chem., 1979, 965.
IRo M. Augustin and S. Bielka, 2. Chem., 1980, 20, 96.
I n ' P. Meunier, Bull. SOC. Chim. Belges, 1979, 88, 3 2 5 .
N. N. Alekseev and S. V. Tolkunov, Khim. Geterotsikl. Soedin., 1979, 1424.
C. Madec, A. Laouenan, and J . Courtot-Coupez, J. Chem. Res. ( S ) ,1979, 230.
D. Binder, C. R. Noe, and G. Habison, Arch. Pharm. (Weinheim, Get.), 1979, 312, 853.
'" N. Ya. Kvitko, R. V. Khozeeva, N. S. Fedorova, V. A. Smirnova, and A. V. El'tsov, Khirn.
Et0,C T J H Et0,C K N
An important paper describes the synthesis of thieno[2,3-d]- and thieno[3,2-

d]-isothiazoles from 2,3-disubstituted thiophens that contain a sulphur function
(SH, SMe, or SCN) and a carbonyl group (CHO or Ac). It was found that methods
used to prepare 1,2-benzisothiazoles often were inapplicable in the thiophen
series. However, heating (176) in an inert solvent gave (177), while the ( E ) - 3 -
mercaptothiophen-2-carbaldoxime,in hot acetic acid and acetic anhydride, gave
the 2,3-dideuterio-isomer. Thieno[3,2-~]isothiazoleswere also prepared by
treating a methyl (2-mercapto-3-thienyl) ketone with a chloroamine. The prod-
ucts obtained by selective S- alkylation of 3,5-bis(sodiomercapto)isothiazole-4-
carbonitrile with ethyl bromoacetate and methyl iodide were cyclized to 4-
aminothieno-[3,2-d]- or -[2,3 -c ]-i~othiazoles.~
The oxidative ring-closure of (178) gave (179), and similarly (180) was
obtained from 3,4-diamino-2,5-dithiocarbamino-thieno[2,3-~]thiophen.l X h The
synthesis of substituted ( 3 H ) -thieno[2,3-d]imidazc-les has been achieved by a
Curtius rearrangement of (181).76
RrjNx
C,H,OEt-p
Ys /d T = J $' NEt2
NH* NH,
(180) (181)
The non-classical system (182) has been synthesized, starting from 43-
and characterized by the isolation of its
bis<chloromethyl)-l,2,5-thiadiazole,
dimer and adducts. 187 The more complex but stable non-classical thiophens
(183)--(185) have been prepared, starting from azomethine imine ylides,
generated in situ from 1-aminopyridinium, 1-aminoquinolinium, or
lRh G. Seybold and H . Eilingsfeld, Liebigs A n n . Chern., 1979, 127 I .

M. Behforouz and R. Benrashid, Tetrahedron Left., 1979, 4193.
Fiue-Membered Rings: Thiophens and their Se and Te analogues 101
2-aminoisoquinolinium salts, followed by cycloaddition to dibenzoylacetylene

and reaction with P4Sloin pyridine. The cycloaddition reactions of (183)-(185)
were investigated. '"
6 Thiophens Fused to Six-membered Heteroaromatic Rings

Thiophen Analogues of Quino1ine.-Cyclization of (96) by treatment with A1Cl3
gave 4-amino-5-cyanothieno[2,3-b]pyridines. 4-(Acylamino)thieno[2,3-b]-
pyridines were obtained from (186).'* 4-Amino-5-cyanothieno[2,3-
blpyridones were synthesized from 2-amino-3-cyanothiophens and ethyl
cyanoacetate in the presence of sodium e t h ~ x i d e . ~ These
~ , ' * ~compounds showed
antibacterial activity.lS9 Through the reaction of 2-chloro-3-cyano-pyridines
with ethyl thioglycollate followed by base-catalysed ring-closure, 3-
aminothieno[2,3-b]pyridines were prepared,'" and these were transformed into
various derivatives, including tricyclic systems. 19'
0
The potent cyclic AMP phosphodiesterase inhibitor (187) was cleaved to (188)
and SO, when treated with sodium methoxide in methanol. The reaction mechan-
ism has been Irradiation of the pyridinium ylides prepared from
thieno[2,3-b]- and thieno[3,2-b]-pyridine by N-amination with O-rnesityl-
enesulphonylhydroxylamine, followed by treatment with base, resulted in the
formation of the corresponding thieno[2,3-c]- and thieno[3,2-c]- 1H-1,2-
diazepines. l g 3 From these compounds the corresponding 3H- derivatives, such as
(189), were prepared; upon photolysis, these gave 3-vinyl-lH-thien0[2,3-c]-
pyrazole, while thermolysis yielded 3-(3-thienyl)pyrazole. The 3-acetoxy- and
3-methoxy-derivatives of 3H- 1,2-thienodiazepines were also prepared, and
their photolyses gave 3-vinylpyrazole, while thermolysis and treatment with base
resulted in loss of nitrogen to give compounds such as (190).'94
K. T. Potts, H. P. Youzwak, and S. J. Zurawel, Jr., J. Org. Chem., 1980, 45, 90.
P. M. Gilis, A. Hafrners, and W. Bollaert, Chim. Ther., 1980, 15, 185.
190 V. I. Shvedov, T. P. Sycheva, and T. V. Sakovich, Khim. Geterotsikl. Soedin., 1979, 1331.
191 V. I. Shvedov, T. P. Sycheva, and T. V. Sakovich, Khim. Geterotsikl. Soedin., 1979, 1336.
19' E. A. Harrison, Jr., and K. C. Rice, J. Org. Chem., 1979, 44, 2977.
193 T. Tsuchiya, M. Enkaku, J. Kurita, and H. Sawanishi, Chem. Pharm. Bull., 1979,27,2183.
194 T. Tsuchiya, M, Enkaku, and H. Sawanishi, Chem. Pharm. Bull., 1979,27,2188.
Thiophen Analogues of 1soquinoline.-Thermal decomposition of vinyl azides,

prepared by condensation of ethyl azidoacetate with thiophen aldehydes that
have ortho-methyl groups, provides a simple and general synthesis for thiophen
analogues of isoquinolines. 195 A new synthesis of thieno[3,2-~]pyridinesconsists
of the thermal rearrangement of (191) to (192), then its bromination with
N-bromosuccinimide, followed by heating at 120 "C in DMF in the presence of
DABC0.89 Photolysis of tetrachloro-4-(phenylthio)pyridinegave (193), and
the perchloro-2-(phenylthio)pyridine gave the corresponding perchloro-
ben~othienopyridine.'~~ Thieno[3,2-~;4,5-~']dipyridine has been prepared by
photolysis of 4,4'-thiodipyridine.197 Photolysis of 7-methylthieno[2,3-c]pyridine
N-imides resulted in rearrangement with ring-expansion to give 1H-1,3- and
3 H -2,3-thieno[2,3-d]diazepines.198
Pyrimidine-fused Systems.-Starting from the corresponding 2-amino-3-

cyanothiophen, (194) has been prepared.'99 Compounds such as (195) have been
transformed into (196) and further derivatives of this system.20"
Miscellaneous Fused Systems.-The reaction of 2-vinylthiophen with azodicar-

boxylates gave a mixture of tetra- and dihydro-thienopyridazine diesters; upon
dicarbethoxylation with TFA followed by oxidation, these gave thieno[2,3-
clpyrida~ine.~"Thieno[2,3-b]pyrazine has been synthesized from 2-chloro-3-
cyanopyrazine by reaction with ethyl thioglycollate and condensation with base
195 T. L. Gilchrist, C . W. Rees, and J. A. R. Rodrigues, J. Chem. SOC.,Chem. Commun., 1979, 627.
J. Bratt, B. Iddon, A. G. Mack, H. Suschitzky, J. A . Taylor, and B. J. Wakefield, J. Chem. SOC.,
Perkin Trans. 1, 1980, 648.
19' J. E. Rockley and L. A. Summers, Chem. Znd. (London), 1979,666.
lgR T'. Tsuchiya, M. Enkaku, and H. Sawanishi, Heterocycles, 1979,12, 1471.
199 A. S. Noravyan, A . P. Mkrichyan, R. A. Akopyan, and S. A. Vartanyan, Khim.-Farm. Z h . , 1980,
14, 37.
V. I. Shvedov, T. P. Sycheva, and T. V. Sakovich, Khim. Geterotsikl. Soedin., 1979, 1340.
'O1 G. Jones and P. Rafferty, Tetrahedron, 1979, 35, 2027.
to yield 3-amino -2 -carbe thoxythieno [2 ,3- b ]p yrazine, followed by removal of the
amino-group via diazotization and hydrolysis and decarboxylation.202Treatment
of (197) with nitrous acid gave (198), which upon thermolysis gave the unstable
( 199).*03Two borazaro-analogues of a dithienobenzene (200) have been pre-
pared from bis[3 - (3- thienyl)-2-thienylammonium] hexachlorostannate(1v) and
arylboron dichlorides. Their spectroscopic properties were
N=B N=N
I I (1 98)
(199)
H OH
(197)
7 Selenophens and Tellurophens

Monocyclic Se1enophens.-Selenophen has been prepared from butadiene and
selenium dioxide.*" Selenophen-3-malonic esters have been prepared by con-
densation of 1,4-dichlorobut-3-en-2-onewith malonic esters followed by
reaction with sodium selenide and cy~lization.~ 2-(2-Selenienyl)-3,4-dicarbeth-
oxyfuran has been prepared analogously to the thiophen d e r i ~ a t i v e . 'The
~~
transient absorption spectra in the flash photolysis of selenophen have been
studied.20"Butyl-lithium and phenyl-lithium attack 2,5-dimethoxyselenophen at
the selenium atom, giving dibutyl selenide and diphenyl selenide, respectively,
together with some diene~.~"' Quantitative studies of the acid- and base-catalysed
hydrolyses of ethyl selenophen-2-carboxylate, of the reactions of selenophen-2-
sulphonyl chloride and of 2-(chloromethyl)selenophen with aniline, and of
selenophen-2-carboxaldehyde with aniline and with a phosphorus ylide have
been carried out. The results were rationalized by correlation analyses with polar
or electrophilic constants of heterocycles, depending on the electron demand of
the side-chain.*08
Condensed Se1enophens.-The reaction of phenylacetylenesulphonamide with
selenium dioxide and hydrogen bromide gave 3-bromo-2-benzo[b Jselenophen-
~u1phonamide.l~~ Heating of (165) with selenium gave (201).169The reaction of
2,3-dimethylselenophen-5-thiolwith methyl y-chloroacetoacetate, followed by
cyclization with PPA and hydrolysis, gave 4,5-dimethyl-3-selenolo[2,3-6]-
(201)
202 J. Bourguignon, M. Lernarchand, and G. QuCguiner, J. Heterocycl. Chem., 1980, 17, 257.
203 J. W. Barton and D. J. Lapham, Tetrahedron Lett., 1979, 3571.
204 S. Gronowitz and I. Ander, Chem. Scr., 1980, 15, 23.
205 E. Sh. Mamedov, S. B. Kurbanov, R. D. Mishiev, and T. N. Shakhtakhtinsk-ii, Zh. Org. Khim.,
1979,15,1554.
206 S. L. N. G. Krishnamachari and T. V. Venkitachalarn, Chem. Phys. Lett., 1979,67, 69.
207 S. Gronowitz, A. Hallberg, and T. Frejd, Tetrahedron, 1979, 35, 2607.
208 A. Arcoria, E. Maccarone, and A. Mamo, J. Chem. SOC.,Perkin Trans. 2, 1979, 1347.
104 He te rocy c Eic Chemistry
thiophenacetic 3-Bromoseleno[2,3-b]selenophen has been prepared

from 3-bromo-4-selenienyl-lithium by successive reaction with DMF, butyl-
lithium, selenium, and ethyl bromoacetate, followed by alkaline ring-closure
and decarboxylation of the 3 -bromo-selenolo[2,3-b]selenophen-5 -carboxylic
acid.210 2-Selenienyl thiocyanates with an amide function in the 3-position
rearranged to selenolo[3,2-d]thiazoles. Also, selenolo[3,2-e]- 1,4-thiazines have
been prepared.71 Treating benzo[b]selenophen-3(2H)-one with semicarbazide
gave the semicarbazone; upon treatment with SeO, in acetic acid, this yielded
benzo[b]selenopheno[3,2-d]- 1,2,3-~elenadiazole.~' '
Te1lurophens.-The '*'Te n.m.r. spectra of 2- and 3-monosubstituted
benzo[b]tellurophens have been determined and found to show large substituent
shifts. Comparisons of the 12'Te n.m.r. parameters of these compounds with those
of tellurophens and with the 77Sen.m.r. parameters of benzo[b]selenophens were
carried out.212
PART 11: Systems containing Nitrogen and Sulphur, Selenium, or Tellurium

by P. A. Lowe
1 Introduction and Reviews

The presentation of material in this section follows the arrangement adopted in
the previous volume of these Reports.
Parts 2 and 3 of the comprehensive review of the chemistry of thiazole have
appeared;' these include chapters on meso-ionic thiazoles and on cyanine dyes
derived from thiazolium salts, and also one on selenazole and its derivatives. The
chemistry of selenazole is also included in a review of selenium-nitrogen
heterocycles.2 An account of the chemistry of thiazolidin-4-ones (which includes
2,4-diones but not rhodanine and i~orhodanine)~ updates an earlier re vie^.^
Reviews on cyclic sulphur-nitrogen compounds5 and on the synthesis and trans-
formations of nitrogen- and sulphur-containing bicyclic heterocycles6 have
appeared. More general reviews, which contain chemistry relevant to this section,
cover reactions based on the onium salts of aza- aromatic^,"^ the synthesis of
'09 N. N. Alekseev and A. R. Kirilash, Khim. Geterotsikl. Soedin., 1979, 1424.
Ya. L. Gol'dfarb, V. P. Litvinov, and I. P. Konyaeva, Khim. Geterotsikl. Soedin., 1979, 1072.
'" B. P. Litvinov and I. A. Dzhurnaev, Izv. A k a d . Nauk SSSR, Ser. Khim., 1979,478.
'12 T. Drakenberg, A.-B. Hornfeldt, S. Gronowitz, J. M. Talbot and J.-L. Piette, Chem. Scr., 1978-9,
13,152.
'The Chemistry of Heterocyclic Compounds', Vol. 34, Parts 2 and 3, 'Thiazole and its derivatives',
ed. J. V. Metzger, Wiley-Interscience, New York, 1979.
' I. Lalezari and A, Shafiee, A d v . Heterocycl. Chem., 1979, 24, 109.
G. R.Newkome and A. Nayak, Ado. Heterocycl. Chem., 1979, 25, 84.
F. C. Brown, Chem. Rev., 1961,61,463.
I. Haiduc, Method. Chim., Part B, 1978, 7 , 789.
B. Stanovnik and M. Tisler, Ado. Pestic. Sci., Plenary Lect. Symp. Pap. Int. Congr. Pestic. Chem., 4th,
1978, 2,65 (ed. H. Geissbuehler, Pergarnon, Oxford) (Chem. Abstr., 1979, 91,74 494).
' T. Mukaiyama. Angew. Chem., Znt. Ed. Engl., 1979,18, 707.
T. Mukaiyarna, Pure Appl. Chem., 1979, 51, 1337.
Five-Membered Rings: Systems containing N a n d S, Se, or Te 105
five-membered heterocycles with several heteroatoms,' ring-opening of azoles
by means of amino-containing reagents,1° and reactions of acetylenecarboxylic
esters with nitrogen-containing heterocycles."
2 Isothiazoles
Synthesis.-From 1,2-Dithiolans (Type C,.* The general synthesis of
isothiazoles from 1,2-dithiolans (see 'Organic Compounds of Sulphur, Selenium,
and Tellurium,' volumes 2, 3, 4, and 512) continues to be exploited. The 1,2-
dithiolylium-4-olates (1) are cleaved by ammonia and subsequently cyclize to
give isothiazol-4-01s (2; X = OH). Methylation in HClO, gives (3), which are
convertible into (4) by base.13
0- -0
X R' HO R'
S'2.S '--i
S' CI0,- S'
(1) (2) (3) (4) (5)
From P-Aminocrotonates (Type C). A one-step synthesis of glycosylamino-

isothiazoles (5) involves the reaction between a glycosyl isothiocyanate (RNCS)
and MeC(NH2)=CHCOzEt.'4
From Benzothiazolyldithioatetidinone (Type C ) . The disulphides (6), which are
obtained by the reaction of penicillin sulphoxides and 2-mercaptobenzothiazole,
give different products with bases, dependent on the structure of the substituents
on the p-lactam nitrogen; e.g., [6; R = CH(C02H)C(Me)=CH2]gives (7) whilst
[6; R = C(=CH2)C02CH2CC13]gives (S)."
* The definitions of types A, B, C, etc. are shown on p. 110 of Volume 1 of this series.
V. P. Semenov, A . N. Studenikov, and A. A . Potekhin, Khim. Geterotsikl. Soedin., 1979,579 (Chem.

Abstr., 1979, 91, 91 524).
A . Antonova and D. Simov, Khim. Geterotsikl. Soedin., 1979, 1587 (Chem. Ahstr., 1980, 92,
110 883).
R. M. Acheson and N. F. Elmore, Adu. Heterocycl. Chem., 1978,23, 263.
12
See ref. 1 of Part I1 of Chapter 3 in Volume 1 of this series.
l3 D . Barillier, Bull. SOC.Chim. Fr., Part 2, 1979, 26.
l4 H. Takahashi, N. Nimura, and H. Ogura, Chem. Pharm. Bull., 1979,27, 1147.
l5 T. Gunda, C. Jaszberenyi, E. R. Farkas, and R. Bognor, Magy. Kcm. Foly., 1 9 7 9 , 8 5 , 2 8 4 (Chem.
Abstr., 1980, 92, 22 321).
From y-Aminoalkyl Thioethers (Type C ) . Oxidation of methionine with iodine
gives S-methylisothiazolidinium-3-carboxylate(9). This is a general reaction for
compounds having an amino-group that is y to a thioether function, and thus
forms a convenient route for the preparation of N-protonated cyclic
sulphilimines.'6
From Thione S-Imides (Type D).Further details of the cycloadditions between
activated alkenes and thione S-imides (see Vol. 1, p. 112, ref 16) have been
reported . I 7
From 0-Aryl-oximes and Alkanethiols (TypeE ) .4-Amino-isothiazoles (2; X =
NH2) are obtained from the reaction between ArON=CR'CN and R2CH2SH,
via the intermediates R2CH2SN=CR'CN,'' and these have subsequently been
converted into various bicyclic isothiazoles (see later).
Reactions of 1sothiazoles.-Photolytic. Whilst photoisomerization of isothia-
zoles to thiazoles is well documented, examples of this reaction occurring with
isothiazol-3(2H)-ones have not previously been reported. Irradiation of (10;
R = alkyl or Ph) gave the corresponding thiazolone (ll)."The isomerization
probably involves homolysis to a biradical, which cyclizes to an a-lactam and
subsequently undergoes ring-expansion. Support for the homolytic step comes
from the isolation of a small amount of (12) from the photolysis of (10; R = Ph).
Ring-expansion Reactions. The isothiazolium salt (13; X = CH) undergoes ring-

expansion to (14; Z = N) on treatment with cyanide ion and also to (14;
Z = CC02Me) with Me02CC-C-,20 as shown in Scheme 1.
Z =NorC-C02Me (14)
Scheme 1
3-Hydroxy-isothiazoles (15) undergo ring-expansion under Vilsmeier reaction

conditions (using R3R4NCHO) to give the corresponding thiazine derivatives
(16).21
l6 D. 0. Lambert and D. W. Swank, J. Org. Chem., 1979,44,2632.

T. Saito and S . Motoki, J. Org. Chem., 1979, 44, 2493.
K. Gewald and P. Bellmann, Liebigs Ann. Chem., 1979, 1534.
l9 J. Rokach and P. Hamel, J. Chem. SOC.,Chem. Commun., 1979,786.
2o J. Rokach, P. Hamel, Y. Girard, and G. Reader, Tetrahedron Lett., 1979, 1281.
K. Tomita and T. Murakami, Jpn. Kokai Tokkyo Koho 79 20 504 (Chem. Abstr., 1979,91,157 755).
Five-Membered Rings: Systems containing N and S, Se, or Te 107
Ring-opening Reactions. Isothiazolium salts undergo ring-opening with HzS to

give either 1,2-dithioles or acyclic reduction products, depending on the nature
of the substituent attached at the nitrogen. Their reaction with sodium benzoyl-
acetate gives 2-ben~oyl-thiophens.~’
3 1,2-Benzisothiazoles
Synthesis.-A novel method of formation of 3-methyl-1,2-benzisothiazole (17 ;
R = Me) is by thermal decomposition of the benzothiadiazepine (18), obtained
by the reaction of 2-NCSC6H,COMe with NH2CONHNH2.23Oxidation of (17;
R = Me) to (17; R = CHO) takes place with Iz in DMSO, and to (17; R =
C 0 2 H ) using SOClz and alkali.
Cyclopalladiation of PhCH=NPh gives a dimeric complex which, on treat-
ment with Et4N’ Me,NC(S)S-, gives (19). The reaction of this organometallic
complex with thiocyanogen gives 2-NCSC6H4CH=NPh, which cyclizes with
HC104 to give the salt (20).24
The N-monosubstituted 2-cyanobenzenesulphonamides (21; R = Me,
CHMe2, or CH2Ph) are isomerized to 1,2-benzisothiazole 1 , l -dioxides (22) on
treatment with Et,N; the reverse process may also be induced by Et,N or by
eF
heating. However (21; R = CMe3, adamantyl, or Ph) are not isomerized under
p)-yl m/;4-
these c~nditions.~’
S - NMe, NH
O C N
\
(19)
NPh
\ s
(20)
‘ (21)
S0,NHR ‘ s
(22) O2
Reactions of 1,2-Benzisothiazoles.-The reaction of 3-chloro-1,2-benziso-

thiazole (17; R = C1) with diethyl malonate in the presence of tetra-alkylam-
monium salts and alkali gives rise to (23) as the main product. A possible
mechanistic pathway is shown in Scheme 2.26
Replacement of the chlorine of 3-chloro-1,2-benzisothiazolium
salts (24) takes
place on treatment with N-mono- or NN-di-alkylanilines, giving the salts (25);
these decompose thermally, with the loss of RICl, and are converted into
benzophenone derivatives 2-R’NHSC6H4COC6H4NR2R3-4 with alkali.27
22 M. E. R. Hassan, Diss. Abstr. Int. B., 1977, 37, 5667.
23
K . Clarke, B. Gleadhill, and R. M. Scrowston, J. Chem. Res. ( S ) , 1979, 395.
24 R. C. Davis, T. J. Grinter, D. Leaver, and R. M . O’Neil, Tetrahedron Lett., 1979, 3339.
25 D. Balode, Sint. Issled. Biol. Soedin., Tezisy Dokl. Konf. Molodykh Uch., 6th, 1978, 28 (Chem.
Abstr., 1980, 92, 180 415).
26
F. Mossini, M. R. Mingiardi, E. Gaetani, M. Nardelli, and G. Pelizzi, J. Chem. Soc., Perkin Trans. 2,
1979, 1665.
” H. Boeshagen and W. Geiger, Chem. Ber., 1979,112,3286.
(17; R
7; R = Cl)
T-
t-
H+
CO,Et
o:
Scheme 2
The reaction of (24) with active-methylene compounds, e.g. R'Me (R2 =

pyridyl or quinolyl), gives rise to the derivatives (26), possibly via the inter-
mediate (27).28
3-Aryl derivatives of saccharin (28) may be obtained by lithiation followed by
reaction with aryl
4 1,2-Benzisoselenazoles
The reaction of 1,2-benzisoselenazolin-3-one (29; R = H) with acetic anhydride
and potassium acetate gives the benzoselenophens (30;R' = H , R2 = OAc, OH,
or NHAc), (30; R' = OAc, R2 = H), and (30; R' = CONH2, R2 = OH),
whereas the reaction of (29; R = Me) under these conditions gives 2-
MeNHCOC6H4SeCH2C02Htogether with the benzoselenazepine (31).30
28 H. Boeshagen and W. Geiger, Synthesis, 1979, 442.

29 A. L. Borror, L. Cincotta, E. W. Ellis, J. W. Foley, and M. M. Kampe, U.S. P. 4 181 660/1980
(Chern. Abstr., 1980,92, 146 747).
30 R. Weber and M. Renson, Bull. Sor. R . Sri., Liege, 1979,48,146 (Chern. Ahstr., 1980,92,110 771).
(31)
5 2,l-Benzisothiazoles
Photochemical irradiation of 2,l-benzisothiazole (32; R = H) and some 3-
substituted analogues gives rise to substitution and/or ring-opening. Irradiation
of (32; R = H) in benzene-Et2NH iives, after acetylation, 2-(acety1amino)ben-
zaldehyde, whilst (32; R = C1) gives a mixture of (32; R = NEt,) and NN-
diethylthioanthranilamide, this last compound not being obtained by irradiation
of (32; R = NEt,). However, photolysis of (32; R = C1) in methanol yields a
mixture of (32; R = OMe) and methyl anthranilate, which can be obtained from
(32; R = 0 ~ ~ 1 . ~ 1
The novel zwitterion (33), formed by the reaction of cyclohexanone with a
mixture of sulphur, carbon disulphide, and ammonia, reacts with aldehydes
R I C H 0 to give (34; R2 = H) and with more carbon disulphide to give (34;
R'R' = s ) . ~ *
S-
6 Other Condensed Ring Systems incorporating Isothiazole

Heteropentalenes.-N-2-Methylation of arylhydrazones of isothiazole-5-
aldehyde, using methyl fluorosulphonate, gave salts which react with aqueous
sodium bicarbonate to give the thiatriazapentalenes (35; X' = N, X2 = NAr),
and similar treatment of the aldoxime gave the oxathiadiazapentalene (35 ;
X' = N, X2 = 0 ) ;this is the first report of this heterocyclic system. The reaction
of the aldehyde derivative (36) with aqueous MeNH2, NaSH, and NaOH gave
the heteropentalenes (35; X' = CH, X2 = NMe), (35; X' = CH, X2 = S ) and
(35; X' = CH, X2 = 0),r e ~ p e c t i v e l y . ~ ~
31 B. Jackson, H. Schmid, and H. J. Hansen, Helv.Chim.Acla, 1979,62, 391.

'' T. Takeshima, K. Tazaki, N. Fukada, and M. Muraoka, J. Chem. Res. (S),1979,410.
33 A. G. Briggs, J. Czyzewski, and D. H. Reid, J. Chem. SOC.,Perkin Trans. 1 , 1979, 2340.
Isothiazolo[5,4-b]pyridines.-Compounds of this type, i.e. (37; R = alkyl), may
be readily obtained by the reaction of 5-amino-isothiazoles with
EtOCH=CRCH0.34
Isothiazolo[3,4-c]pyridazines.-2-Amino-3-cyano-pyridazines, on treatment
with H2S followed by oxidation with H202,give the products (38; R’ = Ph,
R 2 = H or Ph), which revert to the starting compounds on heating to 200°C,
with the elimination of
Me
(39)
Isothiazolo[3,4-d]pyridines.-The reaction of uracils with glycosyl isothiocyan-

ates (RNCS) gives the 3-glycosylamino-5,7-dimethylisothiazolo[3,4-~]pyrimi-
dine-4,6-diones (39).14Similar compounds (39; R = SMe) are obtained from the
reaction between uracils and carbon disulphide, dimethyl sulphate, and alkali.36
7 Thiazoles
Synthesis.-(Type A ; S - C - N + C-C).* The formation of thiazoles by the
reaction of thiourea and its derivatives with a-halogenated ketones continues to
be a popular synthetic method,3741 whilst aryl(dichloromethyl)carbinols,42
bis(chloronitroso)-compounds,43 and a - c h l o r o - e p o x i d e ~ have
~~ also been
utilized.
Type C Syntheses (C-C-N-C + S ) . The reaction of the isocyanide
Me,NCH=C(NC)CO,Et with hydrogen sulphide gave ethyl thiazole-4-carboxy-
late4’ whereas MeCH(NC)CN gave 5 -amino-4-methylthiazole under similar
conditions.46 Ethyl 5-aminothiazole-4-carboxylateis obtained similarly from
Et02CCH(CN)N=CHOEt and hydrogen ~ u l p h i d e . ~ ~
34
C. Skoetsch and E. Breitmaier, Synthesis, 1979, 370.
35
K. Gewald and J . Oelsner, J. Prakt. Chem., 1979, 321, 71.
36
H. Okuda, Y. Tominaga, Y. Matsuda, and G. Kobayashi, Heterocycles, 1979, 12, 485; Yakugaku
Zasshi, 1979, 99, 989 (Chem. Abstr., 1980,92, 128 845).
37
A. N. Mirskova, G. G. Levkovskaya, J . D. Kalikhman, and M. G. Voronkov, Z h . Org. Khim., 1979,
15, 2301 (Chem. Abstr., 1980, 92, 128 792).
38
Y-I. Lin, C. M. Seifert, S. M. Kang, J. P. Dusza, and S. A. Lang, J. Heterocycl. Chem., 1979,16,1377.
39
V. H. Patil, R. A. Mane, and D. B. Ingle, Indian J. Chem., Sect. B., 1978, 16, 1114.
40
J . P. Nath, M. Dash, D. N. Rout, and G. N. Mahapatra, Indian J. Chem., Sect. B., 1979, 18, 384.
41
1. Barta, G. Arnbrus, G. Horvath, M. Soti, and P. Sohar, Acta Chim. Acad. Sci. Hung., 1978,98,463.
42
Ya. G. Bal’on, M. D. Shul’man, and N. V. Kuznetsov, Z h . Org. Khim., 1979,15,2351 (Chem.Ahstr.,
1980,92, 128 793).
43 J. Beger, C. Thielernann, and P. D. Thong, J. Prakr. Chem., 1979, 321, 249.
44 A. A. Durgaryan, G. E. Esayan, and R. H . Arakelyan, Arm. Khim. Zh., 1979,32,29 (Chem.Absrr.,
1979,91, 123 664).
45 U. Schoellkopf, P. H . Porsch, and H. H. Lau, Liebigs A n n . Ckem., 1979, 1444.
4h U. Schoellkopf and K. Hantke, Liebigs Ann. Chem., 1979, 1602.
47 A. K. Sen and G. Chattopadhyay, Indian J. Chem., Sect. B, 1979, 17, 222.
Type FSyntheses (C-N-C--S + C ) . Further examples of the use of salts of
cyanodithioiminocarbonates to give 2-alkylmercapto-4-amino-5-substituted
thiazoles have been rep~rted,'~-~'and the reaction between benzamidines
PhC(NHAr)=NC(S)NHPh and bromonitrobenzene (or phenacyl bromide) to
give 2-arylamino-5-nitro(or -benzoyl)-4-phenylthiazole has been investigated.
Similar products may be obtained starting from PhC(OMe)NC(S)NHPh.S1
Type K Syntheses (C- C - N - C - S ) . N-Thiobenzoyl-a-amino-acids( e . g .
thiohippuric acid) cyclize in the presence of a Vilsmeier reagent to give 5-chloro-
cl-formy1-2-phenylthiaz0le.~~Treatment of the sarcosine derivative
HC(S)NMeCH2C(S)NHMe(A) with trifluoroacetic acid gives the thiazolium salt
(40; R' = Me, R2 = H, X = 02CCF3) whereas its oxygen analogue
HC(0)NMeCH2C(S)NHMe (B) gives the imidazolium salt (41). However, (40)
rearranges irreversibly in aqueous acid to (41) and in base to the meso-ionic
compound (42).Compound (B) is deformylated by base whereas (A) is converted
into (42).53
c,
R ' H NR 2..',.. . F e
S
x- c>
HS-.Fe
' _ _ a
N
x- c1)
,-.N
N
Me
-O
R'
LJR,
's.
Me
Me Me
(40) (41) (42) (43)
Synthesis of Meso-ionic Thiazo1es.-The anhydro-5-hydroxythiazolium

hydroxide (43; R' = SMe, R2 = COCF3) is obtained from the reaction between
sarcosine, carbon disulphide, methyl iodide, and potassium hydroxide, followed
by treatment of the intermediate MeSC(S)NMeCH,CO,H (A) with
trifluoroacetic a n h ~ d r i d e . 'Methanolysis
~ of (43) gives the methyl ester of the
intermediate (A), whilst photolysis yields F3COCH(C02Me)NMeCS2Me.
Physical Properties of Thiazo1es.-An X-ray crystallographic study of the cyclo-
adducts formed from anhydro-4-hydroxythiazolium hydroxide and dimethyl
maleate and dimethyl fumarate indicates that the dipole and dipolarophile
approach in an exo manner, which can be accounted for by steric effects." A
comparison of the melting and clearing points of various 2,4- and 2,5-disub-
stituted thiazoles indicated that the former exhibited no mesophases whilst in
certain cases the latter show liquid-crystalline proper tie^.^^ The 'H-2H exchange
reactions of various 1,3-azolium salts have been studied by the semi-empirical
48 P. Lipka and D. Wobig, Liebigs Ann. Chem., 1979,757.
49 W. Walek and K . Goetzschel, J. Prukt. Chem., 1979, 321, 260.
50 K. Goetzschel, W. Kochmann, M. Pallas, and W. Walek, Ger. (East)P. 131 933/1978 (Chem.Abstr.,
1979, 91, 20 492).
S. Rajappa, M. D. Nair, B. G. Advani, R. Sreenivasan, and J. A. Desai, J. Chem. SOC.,Perkin Trans.
1 , 1979, 1762.
52 I. Ya. Kvitko, V. A. Smirnova, and A. V. El'tsov, Khim. Geterotsikl.Soedin., 1980,36 (Chem.Abstr.,
1980, 92, 215 325); I . Ya. Kvitko, N. S. Fedorova, V. A. Smirnova, R. V. Khozeeva, and A. V.
El'tsov, USSR P. 652 178/1979 (Chem. Abstr., 1979,91, 5221).
53 M . Begtrup, J. Chem. SOC., Perkin Trans. I, 1979, 1132.
s4 H. Gotthardt and F. Reiter, Liebigs A n n . Chem., 1979, 650.
A. Robert, M. Baudy, A. Foucaud, L. Golic, and B. Stanovnik, Tetrahedron, 1978, 34, 3525.
56
K. Doelling, H. Zaschke, and H. Schubert, J. Prukf. Chem., 1979, 321,643.
C N D 0 / 2 method in order to explain the rate enhancement for the thiazolium
~ a t i o n . ~Mass
' spectral analyses of some 4- and 5-acetylthiazoles indicate that
they may be distinguished by this t e ~ h n i q u eThe
. ~ ~relative rates of N-demethyla-
tion of azolium (including thiazolium) salts using triphenylphosphine have been
measured, using 'H n.m.r. spectroscopy, and they show that the demethylation
rates are highest for bases having low pKa values.59 Tautomerism of 2-
aminothiazoles has been investigated using U.V.and i.r. spectroscopies,60 whilst
the latter technique has been used to determine the hydrogen-bonding abilities
and self-association of thiazolidin-2-ones and -2-se10nes.~'An examination of
the base-catalysed 'H-'H exchange in some 2-substituted thiazoles iin
[2H6]DMSO-[2H4]CH30Hhas been reported,62 and the effect of bulky sub-
stituents in the 2- and 4-positions of thiazole on the rate of quaternization
indicates that the 4-substituents have a stronger deactivating effect than those in
the 2-position. Examination of microwave spectra and X-ray crystallography of
the thiazoles and their salts suggests a steric explanation for the o b s e r v a t i o n ~ . ~ ~
Steric effects in the methylation of thiazole and the reverse reaction have been
studied, and they show that the forward reaction is sterically affected but that the
reverse one is
Investigation of the pKa values of some 2- and 5-substituted thiazoles shows
that the pKa is very sensitive to changes of substituent in the 2 - p o ~ i t i o n . ~ ~
Chemical Properties of Thiazo1es.-Reactions of 2-Amino-thiazoles. 2-Amino-
4-phenylthiazole reacts with Vilsmeier reagents to give the 5 -formy1 derivative
in good yield.66 Ethyl 5-aminothiazole-4-carboxylatecan be converted into the
quaternary salt (40; R' = H, R2 = C02Et, X = OTs), which rearranges on
treatment with NaOEt in EtOH into ethyl l-methyl-4-mercaptoimidazole-5-
carboxylate (44); this constitutes a new synthesis of imidazoles starting from
~ ~ interesting rearrangement also occurs on treatment of 2-
t h i a z o l e ~ .An
aminothiazole with a-bromo-P-diketones, as shown in Scheme 3.67
Reactions of Thiazaliurn Salts. The thiazolium salt (45; R = benzyl, X = OH,
Y = C1) catalyses the addition of aldehydes to activated double-bonds, e.g.
&unsaturated acids, esters, and nitriles.68 A novel route to 4-alkyl-2H-
1,4-thiazin-3-ones (46; R = alkyl or benzyl) involves the quaternization of
2-methylthiazole with RI, iodination with I2 and NEt,, and treatment of the
2 - (iodometh yl)t hiazolium iodides with potassium hydroxide,69
A rearrangement that involves ring-contraction takes place on treatment of
compounds (45;R = Me, CH2Ph, or Ar; X = C1; Y = I) with aqueous base,
57 M. M. E. Scheffers-Sap and H. M. Buck, J. A m . Chem. SOC.,1979, 101,4807.
58
H. Demian, M. Coman, A. Muresan, I. Iovanov, and I. Simiti, Org. Mass Spectrom., 1978, 13, 504.
59
J. Kister, U. Berg, R. Galle, and J . Metzger, Bull. Sac. Chim. Fr., Part 2, 1979, 484.
6o I. T. Depeshko and V. I. Treskach, Farm. Zh. (Kiev), 1979, 25 (Chem. Abstr., 1980.92, 180 499).
61
E. Gentric, J. Lauransan, C. Roussel, F. A. Devillanova, and G . Verani, J. Heterocycl. Chem., 1979,
16, 1083.
62
L. Forlani, M. Magagni, and P. E. Todesco, J. Chem. Sac., Perkin Trans. 2, 1979, 1145.
63 G. Pepe, J. P. Reboul, M. Chanon, and R. Gallo, J. Chem. SOC.,Perkin Trans. 2, 1979, 398.
64 L. W. Deady, W. L. Finlayson, and 0. L. Korytsky, Aust. J. Chem., 1979, 32, 1735.
65 L. Forlani, G . Breviglieri, and P. De Maria, J. Chem. SOC.,Perkin Trans. 2, 1979, 163.
66 A. Chatterjee and K. Padhi, Indian J. Chem., Sect. B, 1979, 18, 82.
67
J . F. Robert and J. J. Panouse, J. Heterocycl. Chem., 1979, 16, 1201.
68 H. Stetter, W. Basse, and J. Nieuhaus, Chem. Ber., 1980, 113, 690.
69 M. Hojo, R. Masuda, S. Kosaka, and K. Nagase, Synthesis, 1979, 272.
COR'
HC-COR'
H I t
B-
Scheme 3
and gives rise to thietan derivatives, as shown in Scheme 4.7"The use of

thiazolium salts as catalysts in the benzoin and related reactions has been
extended by the introduction of polymer-supported derivatives such as (45;
R = polystyryl-CH2, X = OH, Y = Cl). These salts appear to be degraded more
rapidly by OH- than by NEt3.71
Reactions ofMeso-ionic Thiazoles. The meso-ionic thiazole (43;R' = Ph, R2 =
H) undergoes photochemical ring-opening to give the keten PhC(S)-
NMeCH=C=O; this can be trapped in ethanol, giving the ester
PhC(S)NMeCH2C02Et.A competing photolytic process generates carbon oxy-
sulphide. A 1,4-cycloaddition of (43;R' = Ph, R2 = H) with singlet oxygen gives
an adduct which loses COS and produces PhC(0)NMeCH0.72
Me
NCHO
Scheme 4 R
'O H. J. Federsel, J . Bergman, and U. Stenhede Heterocycles, 1979, 12, 75 1.
J. Castells, E. Dunach, F. Geigo, F. Pujol, and P. M . Segura, Isr. J. Chern., 1978, 17,278.
'* N. H. Toubro, B. Hausen, N. Harrit, A . Holm, and K . T. Potts, Tetrahedron, 1979, 35,229
8 A2-Thiazolines
Synthesis.-Type A Syntheses (S-C--N + C-C). The reaction between
thioureas RNHCSNH2 and P -aroylacrylic acids gives the A2-thiazolin-5-ones
(47), which may be converted into bicyclic compounds on treatment with hydra-
zine or hydroxylamine (see later).7"'4 However, the reaction with acrylic acid
amides simply leads to transamidation, giving ArCOCH=CHCONHCSNH2.74
Type K Syntheses (C-C-IV-C-S). The reaction between P-(ethoxycar-
bony1)acryloyl isothiocyanates (obtained from the acid chloride and lead
thiocyanate) and aromatic amines gives the 2-arylamino-A2-thiazolin-4-ones (48)
in good yield.75 2-(Substituted amino)-A2-thiazolines may also be obtained in
high yields by allowing vicinal iodo-isothiocyanates to react with amines; e.g.
PhCH(NCS)CH21with amines, in the absence of light, gives (49).76
Physical Properties of A2-Thiazo1ines.-Carbon-13 n.m.r. studies have been

reported on some 4-methyl-2-substituted-A2-thiazolines (and the related
t h i a ~ o l i d i n e s )A. ~mass
~ spectrometric study has been used to distinguish between
the isomers (50; R' = H or alkyl, R2 = aryl) and the corresponding compounds
(51). Conversion of (50) into (51) takes place on reaction with alkyl iodide
followed by thermal decomposition of the salt. Proton n.m.r. studies indicate that
the salts from (50) and (51) have the positive charge on the exocyclic nitrogen
atom.78
Chemical Properties of A2-Thiazolines-The a-thiocarbamoyl-carbodi-imide
Me2NC(S)CMe2N=C=NPr' is in equilibrium with a A2-ttiiazoline dipole (52;
R' = Pr', R2 = Me), as shown by its protonation to (53), its reduction to (54),
and its isomerization to ( 5 5 ) , which further isomerizes to (56).79
2-Alkyl(or -aryl)amino-A2-thiazolines react with methyl and with phenyl
isothiocyanate to give (57; R1 = R2 = Me) and (57;R' = R2 = Ph), and not the
isomeric compounds (58),as previously reported.80The A2-thiazolin-5-one (59)
can act as a protecting agent €or amines, reacting rapidly at room temperature to
give PhCHzSzCNHCH2CONR'R2,which may subsequently be re-converted into
73
A. Sarnrnour, M. Selim, A. F. Fahrny, A . A. Nada, and I. A. Abd Elrnawgoud, Egypt. J. Chetn., 1976,
19, 801 (Chem. Abstr., 1979, 91, 211 312); A . Sarnmour, M. M. Abdallah, A. Essawy, and M.
Elmobayed, ibid., p. 91 1 (Chrm. Abstr., 1980, 92, 41 868).
14
E. A. Solirnan, Ret.. Roum. Chim., 1978, 23, 1597 (Chem. Abstr., 1979,91, 20 069).
75
M. M. Al-Holly. M. Augustin, J. Faust, and M. Koehler, Z. Chem., 1979, 19, 95.
76
R. C. Cambie, H. H. Lee, P. S. Rutledge, and P. D. Woodgate, J. Chem. SOC.,Perkin Trans. I,
1979,765.
77
J. Llinares, R. Faure, and E. J . Vincent, C. R. Hebd. Seances Acad. Sci., Ser. C, 1979, 289, 133.
78
0. V. Agashkin, A. E. Lyuts, V. V. Zamkova, L. A. Tsoi, L P. Krasnornolova, and S. T.
Cholpankulova, Dokl. A k a d . Nauk SSSR, 1979, 245, 114 (Chem. Ahstr., 1979, 91, 4743).
79
E. Schaurnann, H. Behr, and G. Adiwidjaja, Lrehigs A n n . Chem., 1979, 1322.
80
Y. Yamamoto, R . Yoda, and K. Koguchi, Kyoritsu Y a k k a Daigaku Kenkyu Nrmpo, 1978,38 (Chem.
Abstr., 1979, 91, 211 309).
Five-Membered Rings: Systems containing N nnd S, Se, or T e 115
C104 (54)
(53)
C (S)N H R
&RS 1
(57)
NC Bu'
\
c/
162)
(64)
the amine and (59) by means of F,CC02H.8' A*-Thiazoline reacts with alkyl
isocyanates to give the 1-thia-4,7,9-triazaspiro[4,4]nonane-6,8-diones (60),82
whilst spiropyran derivatives, e.g. (6 l ) ,are formed by the reaction of 2-a1k~l-A~-
thiazolinium iodides with salicylaldehydes.x32-Phenyl-A'-thiazoline undergoes
cycloaddition with ketens, e.g. NCC(Bu')=C=O, to give a mixture of bicyclic
and tricyclic products (62), ( 6 3 ) ,and (64).84
9 A'-Thiazolines
The reaction between the thiiran imine ( 6 5 ) and M e C r C N E t , gives the A3-
thiazoline (67) tlia the non-isolable intermediate ( 6 6 ) ;(67)slowly rearranges to
F. E. Roberts, Terruhetiron Lrtt., 1979, 325.
82 H. Giesecke, J . tlockcr. and R. Merten, C k r . Offen. 2 743 516/1979 ( C h e w Abstr., 1979. 91.
39 547).
83 M. Maguet and R. Guglielmetti, Bull. SOC.Chim. Fr., Par1 2, 1978, 539.
x4
E. Schaumann, H. Mrotzek, and F. Assmann, Licbigs A n n . Chem.. 1979. 334.
the aromatic product (68).85The 2,5-epimino-l,4dithian (69), which is formed

from a-mercapto-ketones and ammonia, reacts with acid chlorides or alkyl
isothiocyanates to give the A3-thiazolines (70).8h
The reaction between N-benzoyl-thioureas PhCONHC(S)NHAr and phenacyl

bromide has been shown to give the A4-thiazolines (71), and not the isomeric
thiazoles (72), as previously reported.51 Interaction of phenacyl bromide with
hydrazino-thio(or -dithio)formates RNHNHC(X)S- M' (X = 0 or S) gives rise
to RNHNHC(X)SCH,COPh or the isomeric thiazolidin-2-ones (73; R' = NHR,
X = 0) or the thiones (73; R' = NHR, X = S), which dehydrate under acidic
conditions to the A4-thiazolines (74; R' = NHR, Ar = Ph).X7The reaction
between 4-chloroacetophenone, diaryl-thioureas, and bromine gives rise to only
one isomer (74; R' = substituted aryl, Ar = p-CIC(,H4, X = 0) of the two
possible A4-thiazolines; substituent effects are stated to account for this exclus-
ivity, the aromatic group containing an electron-attracting group becoming
attached to the nitrogen atom of the ring.88 An investigation into possible S-S
and S-0 interactions in some A4-thiazolines (74; R' = Me or Ph; Ar = Ph;
X = NAc, NCSMe, CHCOPh, CHCSPh, etc.) has been carried out, using X-ray
~rystallography.~~
11 Thiazolidines
Synthesis.-Type A Syntheses (S-C--N + C - C ) . The reaction between
thioamides, e . g , MeC(O)CH,C(S)NHPh, and bis(perfluoroketimines)
(F3CN=CF)2 in the presence of a fluoride acceptor gives 4,5-bis(trifluoro-
85 G . L'abbe, J. P. Dekerk, S. Toppet, J. P. Declercq, G. Gerrnain, and M. Van Meerssche, Tetrahedron
Lett., 1979, 1819.
F. Asinger, A. Saus, and M. Psaehr-Wirtz. Liabigs A n n . Chem., 1979, 708.
87 G . Ege, P. Arnold, and R. Noronha, Liebigs Ann. Chern.. 1979, 656.
B. C. Dash and B. B. Nandi. .I. Iridian (?Clem. Soc., 1079, 56, 70.
89 R . J . S. Beer. D. McMonagle, M . S.S . Siddiqui. A . Hordvik, and K . Jynge, Trtrahcdron, 1979, 35,
1199.
Five-Membered Rings: Systems containing N a n d S, St., or Te 117
methy1)iminothiazolidines (75).90 A variety of 5-spirothiazolidin-4-ones (76)

have been obtained by condensation of dibromomalonic acid with substituted
thio~reas.~~
Type B Syntheses ( C - C - N + C-S). Attempts to synthesize 1,3-thiazine

derivatives by the condensation of alkylamines, carbon disulphide, and dialkyl
maleates gave instead the 2-thioxothiazolidin-4-ones (rhodanines) (77).92
Type D Syntheses (C-C--S + C - N ) . Further examples of the synthesis of
thiazolidin-4-ones, by allowing 2-mercaptoacetic acid to react with C=N-
containing compounds, have been reported; with azines, only one of the C=N
groups r e a ~ t e d ; ’ ~with carbodi-imides, 2-iminothiazolidin-4-ones were
~ cyclic ketones and amines, 2-spirothiazolidin-4-ones were pre-
~ b t a i n e d ; ’with
pared.91v95 The reaction between fluorenylidene-anilines (A) and 2-oxothiiran
1,l -dioxide afforded the spiro-thiazolidin-4-one 1,l -dioxides (78), which could
also be obtained by oxidation of the products that were formed by starting from
(A) and 2-mercaptoacetic acid.96
H H
(78)
Type E Syntheses ( N - C - C - S + C ) . The reaction between ketones
RCOCH,R (R = pentyl, hexyl, efc.),ethyleneimine, and sulphur gives a mixture
of 2,2-dialkylated thiazolidines and 5,6-dihydrothiazines, but only the former
products are obtained when HSCH2CH2NH2is A combination of the
azirines (79; R’ = H ; R2 = H or alkyl) or (79; R’ = R2 = Me), 2-hydroxy- or
2-dimethylamino-tetrahydropyran, and hydrogen sulphide produces 2-(4-hy-
droxybuty1)-thiazolidines ( 80).9x
Miscc.1larzeous Syntheses. A novel method for the preparation of 3-(2-amino-
ethyl)-thiazolidine-2,4-dionesinvolves ring-opening (by means of HBr) of the
90 K . Grohe, H. J . Scholl, V. Paul. W. Brandes, and P. E. Frohberger, Ger. Otfen. 2 808 227/1979
(Chem. Ahstr., 1980,92, 41 932).
” R. K. Behera and A. Nayak, Indian J. C h i n . Sect. B., 1979, 18, 141.
92 W . Hanefeld and W . Hinz, Arch. f h a r n ~(W~inheirn,Ger.), 1980, 313, 20.
93
G . Fenech, T. Previtera, M . G. Viyorita, and P. Monforte, Atti Soc. Peloritanu Sci.Fis.,Mar. Nut.,
1977, 23. 165 (Chern. Abstr., 1979,91. 157 646).
94
P. Monforte, G . Fenech, M. Hasile, P. Ficerra, and A. Silvestro. J. Heterocycl. Chem., 1979, 16, 341.
” V . N. Khunt. K. S. Parekh, and A . R. Parikh, J. Indian Cham. Soc.. 1979, 56, 436.
9b M. A. Abou-Gharbia and M. M. JoulliC, Hetm)cyclev. 1979, 12, 909.
97
F. Asinger, J. Stalschus. and A . Sam, Monatsh. C‘hem., 1979, 110, 425.
98
G . Ricart, C. Glacet, and D. Couturier, C. R. Hrbd. Seancm Acud. Sci.. Ser. C, 1979. 289, 297.
118 Heterocyclic Chenzistry
imidazoline ring of imidazo[2,1 -h]thiazoles, e.g. (8l),which had been previously
synthesized from imida~oline-2-thiones.~~
Physical Properties of Thiazo1idines.-An investigation of the charge distribu-
tion in a series of N-alkylated thioureas and related thiocarbonyl compounds
(including thiazolidinethiones), using X-ray photoelectron spectroscopy, has
been described."' Population analysis, which refines the population of the
electrons in a molecule, has been carried out on R-thiazolidine-4-carboxylicacid,
and the results were compared with theoretical calcu1ations.Io1A stereochemical
analysis of 2-aryl-3-(2-pyridyl)-thiazolidin-4-ones,using ' H n.m.r. and i.r. spec-
troscopies, has been reported,lo2and these techniques also give information on
the tautomeric equilibrium of some 2-arylarnino-thiazolidines. '03
A kinetic study, using a radioactive indicator method, of the conversion of

thiazolidine derivatives into mercaptoalkyl-ureas under basic conditions has been
reported . I o 4
Chemical Properties of Thiazo1idines.-Alkylation of metal salts of thiazolidine-

2-thione can yield either N-alkyl derivatives, depending on the type of solvent,
the alkylating agent, and the counter-ion; e.g., the sodium salt with methyl iodide
in dioxan gives mainly the S-methyl compound, whilst with dimethyl sulphate in
DMSO the N-methyl derivative is ~ b t a i n e d . ~Oxidative
"~ imination of the
thiazolidin-4-one (82), using Chloramine-T, gives (83) quantitatively,lo6 whilst
P h ? - S- - ~
(81)
R yJNTOS
(82) x
X
= s
Me0,C
&h S
(84)
(83j X = S=NTos
Ag2C03in dioxan cleaves (84) to give an intermediate that may be methylated
to give MeSCH2CH(C02Me)N=CHPh or which, in the presence of diazabi-
cycloundecene, gives the unstable H2C=C(C02Me)N=CHPh.'"' A stereo-
selective cyclization of certain N-alkyl-4-hydroxythiazolidin-2-oneshas been
described. The reactions of [85; R 1= C H 2 C H 2 C ~ C Hor (E)-CH2CH2-
CR3=CHRJ, R2 = H or Me] (which are obtained from the appropriate thia-
zolidine-2,4-diones) with formic acid gives the bicyclic products (86) almost
quantitative1y.lo8
'' D. C. Rigg, Eur. P. 2978/1979
100
(Chern. Absrr.. 1980,92, 163 0.56).
R . Szargan, R. Scheibe, L. Beyer, Ya. V. Salyn, and V. I . Nefedov, Tetrahedron, 1979, 35,59.
lo' J. Karno. N. Tanaka, Y . Matsuura, T. Ashida, and M. Kakudo, Bull. Chem. Sor. Jpn., 1979,52,706.
M. G . Vigorita, A. Chirnirri, S. Grasso, and G . Fenech, J. Heterocycl. Chern., 1979, 16, 1257.
103
1. N. Azerbaev, L.. A. Tsoi, S. T. Cholpankulova, and V . I . Artyukhin, Khim. Geterotsikl. Soedin.,
1979, 755 (Chern.Ahsfr., 1979, 91, 107 353).
I04
S . V. Volkova, A . A. Mandrugin, and M. N. Sernenenko, Sint. Issled. Biol. Soedin., Tezisy Dokl.
Konf. Molodykh Uch., 6th. 1978, 9 tChern. Ahstr., 1980, 92, 197 490).
105
N. A. Shenberg, S . M. Rarnsh, A . 1. Ginak, and E. G. Sochilin, Zh. Org. Khirn., 1979, 15, 1305
(Chern. Abstr., 1979,91, 157 649).
S. S. Gontar, G. I. Druzhinina, M . M. Krernlev, N. D. Borodavko, and A. P. Kabakov, Khirn.
Geterotsiki. Soedin., 1979, 609 (Chern. .4hstr., 1079. 91, 107 928).
lo' E. Oehler and U. Schmidt, Chem. Ber.. 1979, 112, 107.
I08
J. A . M. Harnersrna, H. E. Schoernaker, and W . N. Speckamp, Tetrahedron Lett., 1979, 1347.
Five-Membered Rings: Systrtns containing N a n d S, Se, or Tt7 119
Rhodanine and Isorhodanine. Alkyla tion of metal salts of 5 -furfurylidene-

dependent on both the nature of the counter-ion and the concentration.'""
A study of the ring-cleavage reactions of 5-arylhydrazone derivatives of
rhodanine (87; X = S, Z = 0)and of isorhodanine (87; X = 0, Z = S) shows
that the former will ring-open with PhCH2NH2 to give PhCH,NHC(O)C(S)-
NHCH,Ph, whilst the latter gives (87; X = 0, Z = PhCH2N). However,
both compounds will ring-open with hydrazine, and both give S-alkyl deriv-
atives with alkyl halides.""
12 Selenazoles
The 2-hydrazino-selenazoles (88; X = Se), and alsG the corresponding thiazoles
(88; X = S), are obtained from the reaction between phenacyl bromides and
seleno- or thio-semicarbazide under alkaline conditions. I ' Selenazolidine-2-
carboxylic acid has been obtained by the reduction of selenocysteamine followed
by treatment with Na02CCH0."2
13 Benzothiazoles
Synthesis.-From ortho-Amino-benzenefh~o~~ (Type A ; S-C6H4-N + C)."
The products that are formed on condensation of ortho-aminobenzenethiol and
aryl isothiocyanates are temperature-dependent. In refluxing ethanol, the
dithioamides (89) may be isolated; in xylene, hydrogen sulphide is eliminated,
giving the 2-(arylamino)benzothiazoles(90).' l 3 The formation of benzothiazoles
containing a 2-chlorofluoromethyl group by condensation of ortho -aminoben-
zenethiols with the 'Yarovenko reagent', Et,NCF2CHC1F, has been
109
A. Macias, D. Torres, and I. P. Beletskaya, Zh. Org. Khim., 1979,15, 665 (Chem.Ahstr., 1979,91,
56 892).
I10
N. A. Kassab, S. 0. Abd Allah, and S. A. Elbahaii, J . Heterocycl. Chem., 1979, 16, 509; 2.
Naturforsch., Teil B, 1979, 34, 507.
111
K . Nalepa and E. Bulka, Acta U n i v . Palacki Olomuc., Fac. Rerutn Nar., 1978,57,191 (Clwm.Abstr.,
1980,92, 215 3 2 6 ) .
112
C. DeMarco, C. Cini, R. Coccia, and C. Blarzino, Ital. J. Riochem., 1979, 28, 104 (Chem. Ahsfr..
1979, 91, 157 669).
I13
B. Arventiev and T. Nicolaescu, Bul. Znst. Polireh. lasi, Serf. 2, 1978, 24, 123 ((%ern. Ahsrr., 1970,
91, 56 901 1.
described,' !4 whilst their reaction with keten SS-acetals, e.g. PhCH-CHCO-
C(CN)=C( SMe 12, gives 2 -[(cinnarnoy1cyano)meth ylene]benzothiazoline.
A new route to 2-chloro-phenothiazines that contain I4C atoms has been
described in which 2-amino-4-chlorobenzenethiol is condensed with
[2-'4C]cyclohexanone to give the spiro-2,3-dihydrobenzothiazole(91); acylation
of (91) followed by treatment with sulphuryl chloride gives a mixture of (92) and
(93).I l h
Type B Syrttheses (C,H,--N-C--S). Further examples of the formation of

substituted 2-aminobenzothiazoles by cyclization (with PPA) of 1-aryl-
thiosemicarbazides have been described. With PhN(Me)NHC(S)NHR (R = H
or Ph), iminobenzothiazolidines (94) are whilst with cyclic
thiosemicarbazides, c.g. (95), a mixture of (96) and (97) was isolated.'" Another
report of the formation of fluorinated benzothiazoles by treatment of acylated
perfluoroaniline with phosphorus pentasulphide has appeared,"' and also of the
oxidative cyclization (using bromine) of aryl-thioureas t o give 2-amino-
b e n z o t h i a z o l e ~ . 'A~ ~one-step synthesis of fluorinated benzothiazolines (98)
involves perfluorobenzene and sym-dialkyl-thioureas in the presence of sodium
hydride in DMF, but some benzimidazolines (99) are also formed.'*' Photo-
chemical cyclodehydrochlorination of ortho-halogeno-thioacetanilides, e.g. 2,3-
and 2,4-C1,C6H,NHC(S)Me, gives good yields of the corresponding 2-methyl-7-
or -6-chlorobenzothiazoles.'?2
n
R
(97) (99)
A. Takaoka, K. Iwarnoto, T. Kitazurne, and N . Ishikawa, J. Fluorine CIwm., 1979, 14, 421.
'Is M. Augustin and G. Jahreis, J . Prakt. Chem., 1979. 321, 699.
I16
R. Muccino, J. Cupano, and A. A. Liebman, J. Heterocycl. Chem., 1979, 16, 605.
N. Yu. Lebedenko, Deposited Document, 1978, VINITI 1805-78 (Chem.Ahstr., 1980,92,94 288).
N. Yu. Deeva, Sint. Issled. Biol. Soedin., Tezisy Dokl. Konf. Molodykh Uch., 6th, 1978. 30 (Chem.
Abstr., 1980,92, 215 323).
11')
Y. Inukai, Y. Oono, T. Sonoda, and H. Kobayashi, Bull. Chent. Soc. Jpn., 1979, 52, 5 16.
I*" D. Sirnov and T. Deligeorgiev, Izu. Khim., 1979, 12, 247 (Chem. Abstr., 1980, 92, 181 067).
12' Y . Inukai, T. Sonoda, and H. Kobayashi, Bull. Chrm. Soc. Jpn., 1979, 52, 2657.
I22
R. Pararnasivarn, R. Palaniappan, and V. T. Ramakrishnan, J. Cham. Soc., Cheni. Commrrn., 1979,
260.
Five-Membered Rings: Systems containirig N a n d S, Se, or Tc 121
An interesting formation of partially hydrogenated benzothiazoles involves the
reaction between 1-trimethylsilylcyclohexene (and its 4-t-butyl derivative) and
iodine/lithium thiocyanate. The reaction occurs i n a highly regio- and stereo-
selective manner to give the adducts (100; R = H or CMe,), which subsequently
react with KOH in MeOH to give (101).'23
Type D Syntheses ( s - c ~ , H , - N - c ) . A novel ring-contraction of benzo-1,2,4-

thiadiazines (102), which extends the scope of a similar benzoxazine reaction,
takes place either thermally, in the presence of tervalent phosphorus compounds,
or photochemically (but in lower yields) to give the benzothiazoles (103).'24
Type G Syntheses (CC,ff5-s-c--N). The reaction between 2-thiocyanato-
cyclohexen-3-one and aniline gives the partially reduced benzothiazole
(104).'"
9S NR
(7; 0 ( I 04)
\)NHPh O Z N
NO2
a
(105)
: D
NHR
O 2 N O N O 2
.- - - ,
NO2
( 106)
M'
Physical Properties of Benzothiazo1es.-Dielectric relaxation studies on benzo-

thiazole have enabled thermodynamic parameters to be determined.12' Treat-
ment of the diary1 sulphides (105; R = Me or Ph) with base gives the spirocyclic
Meisenheimer complexes (106), which were identified by means of n.m.r. and
visible spectroscopies, before rearranging to phenothiazine derivative.127A "C
n.m.r. study of 43 benzothiazole derivatives has given information concerning
substituent effects on prototropic tautomerism and on annulation reactions.12R
Mass spectral studies have been reported on 2-a~etamidobenzothiazole'~~ and
on some 2-(3'-aryl-5'-aminopyrazol-1'-y1)benzothiazoles. 13'
Kinetic studies in the benzothiazole series include examination of the base-
catalysed reaction between 2-fluoro-6-nitrobenzothiazole and aliphatic
a m i n e ~ , ' ~investigation
' of the mechanism of formation of sulphenic acid amides
123 E. J . Thomas and G. H. Whitham, J. Chem. SOC.,Chem. Commun., 1979, 212.
124 V. W. Boehnisch, T. L. Gilchrist, and C. W. Rees, J. Chem. Soc., Perkin Trans. 1. 1979, 2851.
125 Y . Tamura, T. Kawasaki, N. Gohda, and Y. Kita, Tetrahedron Lett., 1979, 1129.
126 P. P. Srivastava, P. Kumar, and S. L. Srivastava, Indian J. Pitre Appl. Phys., 1979, 17, 23.
I27
V. N. Knyazev, V. N. Drozd, and T.Ya. Mozhaeva, Zh. Org. Khim., 1979, 15, 1107 (Chem. Ahsrr.,
1 9 7 9 , 9 1 , 9 1 546).
128
R . Faure, J. Elguero, E. J . Vincent, and R. Lazaro, Org. Magn. Resnn., 1978, 11, 617.
J . L. Aubagnac and P. Carnpion, Org. Mass Spectrom., 1979, 14, 46.
I3O S. P. Singh, R. K . Tomer, O m Prakash, and S. N . Sawhney, Indian. .I. Chem., Sect. R . , 1979,17, 372.
13' L. Forlani and P. E. Todesco, J. Chem. SOC.,Perkin Trans. 2. 1980, 3 13.
by condensation of 2-mercaptobenzothiazole with a m i n e ~ ,and

' ~ ~measurement
of the rates of base-catalysed 'H-2H exchange at C-2 in benzothiazole, benzo-
selenazole, and related The acid-base equilibria of some 2-
substituted derivatives of 7-exo-5,5-dimethyl-4,5,6,7-tetrahydrobenzothiazole
have been investigated spectrophotometrically.134 The role of mercapto-
benzothiazole and its zinc complex as anti-oxidants has been e ~ a 1 u a t e d . l ~ ~
Chemical Properties of Benzothiazo1es.-Substitution Reactions. The reaction
between benzothiazol-2-yl allylic ethers, double Grignard reagents prepared
from w-chloro-alkanols, and cuprous iodide is a highly regio- and stereo-selective
method for the formation of (E)-alkeno1s.'36An example is shown in Scheme 5.
The reaction between 2-(methy1mercapto)benzothiazole and alkyl- or aryl-
magnesium halides in the presence of a nickel complex [NiC12{Ph2P(CH2),PPh2}]
gives 2-alkyl- or 2-aryl-benzothiazoles in greater than 90% ~ie1ds.l~'
BrMg.1,
R = (CH2),0MgBr
1
$0 + (E)-EtCH=CH(CH2)50H
S
Reagents: i, ClMg(CH,),OMgBr, CuI
Scheme 5
2-Chloro-benzothiazoles react with dichlorocarbene under phase-transfer

catalytic conditions to give the corresponding 3 -(dichloromethyl)benzothiazol-2-
ones (107),13'whilst the reaction between benzothiazole and thiophosgene gives
a mixture of 3-formylbenzothiazole-2-thione and ben~othiazole-2-thione.'~~
The Vilsmeier reaction of ethyl benzothiazole-2-acetate gives the enamine (1OS),
which readily reacts with diketen, active-methylene compounds, etc. to give, e . g ,
pyrido[2,1-b]benzothiazoles (see later).140 2-(Morpholinothio)benzothiazole
reacts with cyclic ketones to give products, e.g. (109; R' = H, R2 =
2-thiobenzothiazolyl); on alkylation, this gives (109; R' = alkyl, R2as before),
13* V. A . Ignatov, P. G. Valikov, S. V. Sukhanov, and A . N . Lazovenko, Z h . Obshch. Khirn., 1979,49,
841 (Chem. Ahstr., 1979,91,55 937); V . A . Ignatov, ibid.,p. 1122 (Chem.Ahstr., 1979,91,38 509).
0 . Attanasi, P. Battistoni, and G. Fava, Phosphorus Sulfur, 1979, 5, 305.
'34 V. Zelenska, V. Madajova, and I . Zelensky, Chem. Zvesti, 1978, 32, 658 (Chem. Ahsrr., 1979, 91,
19 560).
13' M. J. Husbands and G. Scott, Eur. Polym. J., 1979, 15, 879 (Chem. Ahsfr., 1980,92, 128 786).
V. Calo, L. Lopez, G. Marchese, and G. Pesce, Synthesis, 1979, 885.
137
H. Takei, M. Miura, H . Sugimura, and H. Okamura, Chem. Lett., 1979, 1447.
j3' A. Arnoldi, P. Galli, and A. Zagni, Heterocycles, 1979, 12, 1335.
13' A . W. Faull and R. Hull, J. Chem. RPS.( S ) , 1979,148.
140 T. Kato, T. Chiba, and T. Okada, Chem. Pharm. BuU., 1979, 27, 1186.
(107) (108) (109)

and these are then converted into the unsaturated ketones (110; R = alkyl) in
good yield, the 2-mercaptobenzothiazole being recovered and re-used.141 N -
Aryl-benzothiazole-2-sulphenamides, which cannot be synthesized directly, can
be obtained by transformation of the N-alkyl-~ulphenamides.'~' The reaction
be tween 2-amino- or 2 -(methylamino)-benzothiazole and 4-chloro-3,s -di-
nitrobenzotrifluoride gives 2-arylimino-3-aryl-benzothiazolinesor 2-methyl-
irnino-3-aryl-benzothiazolines,respectively, by nucleophilic replacement of the
chlorine atom,'43 whilst the reaction of benzoyl chloride with 2-methylbenzo-
thiazole (or 2-methylbenzoselenazole) gives the products (111; X = S or Se); on
alkylation followed by hydrolysis, these give (112; X = S or Se).',' 3-Methylben-
zothiazoline-2-thione reacts with Grignard reagents to give the 2,2-disubstituted
compounds as major and the potassium salt of benzothiazoline-2-
thione has been N-phosphorylated, using phosphorochloridic diamides
(R,N),P(O)Cl. 146
0
( 11 0 )
Alkylation Reactions. Alkylation of the anion of 2-benzothiazolylazophenol

with alkyl halides or diazomethane gives the 3-alkyl derivative (113); this
rearranges, however, to the thermodynamically more stable ether. With benzyl
halides, only the latter compound could be is01ated.l~'
Reactions of Benzothiazolium Salts. The benzothiazolium salt (114; R' = H,
R2 = Me, X = ClO,) reacts with tetraethyl allenetetracarboxylate to give the
stable dipolar product (115),'" whilst a convenient synthesis of a -diazocarbonyl
compounds is by the reaction of acylmethylenetriphenylphosphoraneswith
14'
S. Torii, H. Tanaka, T. Kudai, and S. Watanabe, Chern. L x f f . , 1979, 147.
14* R. J. Arnold, M. I. Gattuso, and J. P. Shoffner, Phosphorus Sulfur, 1979, 5 , 267.
'43 J. J. D'Arnico, C. C. Tung, and W. E. Dahl, Phosphorus Srtlfur, 1979, 7, 19 1.
144 G. Ciurdaru and M. Ciuciu, J. Prakt. Chern., 1979, 321, 320.
14' K. Akiba, H . Shiraishi, and N. Inamoto, Bull. Chern. Soc. Jpn., 1979, 52, 156.
14' T. V. Ratnikova, A. I. Ginak, and V. I. Yakovlev, Khim. Getrrotsikl. Soedin., 1979, 1050 (Chern.
Ahstr., 1980, 92, 41 820).
'41 A. Yu. Errnishov and I. L. Shegal, Khitn. Geterotsikl. Soedin., 1979, 1476 (Chent.Ahstr., 1980, 92,
163 885).
'41 R. Gompper and U . Wolf, Liebigs A n n . Chmi., 1979, 1406.
2-azido-3-ethylbenzothiazolium tetrafluoroborate (114; R' = N3, R' = Et, X =

BF,), followed by hydrolysis. 149 This reagent will also introduce an a-diazo-group
into certain heterocycles, to give, for example, (116; X = 0) or (116; X =
NPh).I5*
Rearrangements. The migratory aptitude of alkyl groups during the Stevens
rearrangement of NN-dialkyl-2-aryl-benzothiazoliumsalts has been investi-
gated. Thus in (117; R' = Et, R' = Me) the ethyl group migrates exclusively,
irrespective of the stereochemistry of the salt, and a proposed mechanism
involves a planar 7-type carbo-cation ir~terrnediate.'~'
R' R2
""'cy;
N,
( 1 16)
\
\ :
(117)
BF,-
Q&le
(118)
The reaction between 2,2-disubstituted benzothiazolines (118; R' = Me or Ph,

R2 = H) and (118; R' = R2 = Me) and halogeno-acyl halides to give 3-0x0-
2,3-dihydro-4H- benzo- 1,4-thiazines appears to involve NS- bis( halogeno-acyl)-
o-aminobenzenethiols as key intermediates. I c 2 The reactions of 3-acyl-2,2-
dialkyl-benzothiazoline sulphoxides (obtained from the benzothiazolines and
m-chloroperoxybenzoic acid) and ace tic anhydride give 4-acyl-benzo-
1,4-thiazines. In this case a sulphonic anhydride is a suggested intermediate
(Scheme 6).153
Ac Ac
2- s 2
1 I OAc I
0 OAc OAc
OAc
Scheme 6
14 Condensed Ring Systems incorporating Thiazole

Structures comprising Two Five-Membered Rings (5,5).--Thiazolo [3,2-d]-
tetrazoles [CN4-C,NS].A I3C n.m.r. study of the products of quaternization
149
M. Regitz, A . M. Tawfik, and H. Heydt, Synrhesis, 1979, 805.
150
A. Schmitz, V. Kraatz, and F. Karte, Heterocycles, 1978, 10, 199
15' K. Akiba, Y . Ohara, and M . Inamoto. Heterocycles, 1978, 11, 231.
152 M. Hori, T. Katanka, H. Shimizu, and Y . Imai, Chum. Pharm. Bull., 1979, 27, 1973.
M. H0ri.T. Kataoka, H. Shimizu, and Y. Imai, Hererocycles, 1978.10, 17; Chem. Yharm. Bull., 1979,
27. 1982.
Fiue-Membered Rings: Systems containing N a n d S, Se, or Te 125
(using Me2S04) of a series of thiazolo[3,2-d]tetrazoles (119) showed that

methylation takes place at both N-7 (mainly) and N-5 ( o c ~ a s i o n a l l y ) . ~ ~ ~
Thiazolo[2,3-c]thiazoles [CzN3-C3NS]. The reaction of 3-mercapto-5-(3-
pyridyl)-l,2,4-triazole with 4-BrC6H,COCH2Br gave the sulphide; this cyclizes
with PPA to give (120), and not (12l).’’’ 2,3-Dihydro-derivatives of the latter
ring system may be obtained from the reaction between acyl-hydrazines and
C1(CH2)*NCSin the presence of Et,N. lS6
(1 19) (120) (121)

Py = 3-pyridyl
Thiazolo[2,3- b]- 1,3,4-thiadiazoles [C2N2S-C3NS]. The reaction between
1,3,4-thiadiazole-2(3H)-thiones and phenacyl bromide gives sulphides, e.g.
(122; R = NHAc), which may be cyclized to the thiazolo[2,3-b]-1,3,4-
thiadiazolium salts (123; R = N H A c ) , ’ whilst
~ ~ with PhCHBrCOCl the anhydro-
S -hydroxy-2-methyl-6-phenylthiazolo[2,3- b]- 1,3,4-thiadiazolium hydroxide
(124; X = N) is readily 0btair1ed.l~~
-0
Thiazolo-[Z73-b]- and -[5,4-d]-thiazoles [C3NS-C3NS].By means of a method

similar to that of the previous reaction, thiazole-2(3H)-thione may be readily
converted into anhydro-3-hydroxy-2-phenylthiazolo[2,3-b]thiazolium
hydroxide (124; X = CH).158 2-Acetylamino-5-amino-4-thiocyanatothiazole
cyclizes, on heating in methyl benzoate, to give the thiazolo[S,4-d]thiazole
derivative (12S).159
Imidazo[2,1- blthiazoles [C3NS-C3N2].Further examples of the reaction
between 2-amino-thiazoles (or -thiazolines) and a-bromo-ketones to give imi-
dazo[2,1 -b]thiazoles (126) have been reported;160-162this ring system has also
been obtained from imidazolidine-2-thione and a - b r o m o - k e t o n e ~ , ’or~ ~pro-
pargyl and from l-(2-methoxyethyl)-4-phenylimidazolidin-2-one
154 R. Faure, J . P. Galy, E. J. Vincent, and J. Elguero, Org. Magn. Reson., 1978, 11, 507.
155 (Miss) Sangita and H. K. Pujari, Indian J. Chem., Sect. B., 1979, 17, 364.
156 L. G . Payne, M. T. Wu, and A. A. Patchett, Heterocycles, 1979, 12, 1171.
157
M. A. Eldawy, S. A. Shams El-Dine, and K. M. El-Brembaly, Pharmazie, 1979, 34, 248.
15’ K. T. Potts and S . Kanemasa, J. Org. Chem., 1979, 44, 3808.
159 G . Seybold and H. Eilingsfeld, Liebigs Ann. Chem., 1979, 1271.
E. Abignente,F. Arena, M. Carola, P. DeCaprariis. A. P. Caputi, F. Rossi, L. Giordano, C. Vacca, E.
Lampa, and E. Marino, Farmaco, Ed. Sci., 1979, 34,417 (Chem. Abstr., 1979,91, 39 390).
Ihl I. T. Barnish, P. E. Cross, R. P. Dickinson, B. Gadsby, M. J . Parry, M. J. Randall, and I. W. Sinclair, J.
Med. Chem., 1980,23, 117.
16’ S. Nielek and T. Lesiak, Collect. Lect. Int. Symp. Furan Chem., 3rd, 1979,224 (Chem. Abstr., 1980,
92, 163 900).
163 G. Ferrande, Fr. Demande 2 414 510/1979 (Chem. Abstr., 1980,92,215 470).
164 K . Wisterowicz and J. Sawlewicz, Acta Pol. Pharm., 1979, 36, 25 (Chem. Abstr., 1979,91, 91 5 5 5 ) .
and P2S5 plus HCl;165in a similar manner to two earlier examples, l-methyl-
imidazole-2(3H)-thione reacts with PhCHBrCOCl to give anhydro-3-hydroxy-
7 -methyl-2 -phen ylimidazo [2,1- b Ithiazolium hydroxide ( 127),166 which may
undergo cycloaddition reactions, with breakdown of the thiazole ring.
An interesting example of ipso-nitration in this ring system has been reported;
treatment of (128; R' = R2 = Br) with sodium nitrite in acetic acid gives (128;
R' = NO2, R2 = Br) whilst (128; R' = R2 = NO2) is obtained at higher tem-
perature~.'~' -0
Pyrrolo[2,3-d]thiazoles [C3NS-C4N].Using a method similar to that previously

used to prepare furano[2,3-d]thiazoles (see last year's Report), 2-pyrrolyl-
thioureas have been cyclized to the hitherto unknown pyrrolo[2,3-d]thiazoles,
e.g. (129).168
Structures comprising One Five-Membered and One Six-Membered Ring
(5,6) .-
Thiazolo [3,2- c][ 1,2,4,6]thia triaz ine [ C3NS-C2N3S]. The react ion
between 2-amino-A2-thiazoline and chlorosulphonyl isocyanate gives the
product (130), and not its isomer (131).'69
(130) (131)
Thiuzolu-[3,2- b]- and - [3,2-c]-[ 1,2,4]triazines [C3NS-C3N3].Examples of the

latter class of compounds are obtained by treatment of
HO2CC(CH=CHR)=NNHCSNH2 (A) with phenacyl bromide, followed by
cyclization of the resulting thiazolylhydrazones to give (132), whilst if (A) is first
cyclized to the triazine and subsequently allowed to react with an a-halogenated
ketone, the isomeric products (133) are obtained.""
lhS S. Raghu, A . Zweig, and W. A . Henderson, Fundam. Res. Homogeneous Caral., 1979,3,565 (Chem.
Absrr., 1980, 92, 94 291).
K. T. Potts and S. Kanemasa, J. Org. Chem., 1979, 44, 3803.
N. Saldabols, E. Liepins, and J. Popelis, Z h . Org. Khim., 1979, 15, 2547 (Chem. Absrr., 1980, 92,
215 393).
l'' L. Grehn, Chem. Scr., 1979, 13,78.
S. Karady, J . S. Amato, D. Dortmund, A. A. Patchett, R. A. Reamer, R. J. Tull, and L. M .
Weinstock, Heterocycles, 1979, 12, 1199.
El Sabai A. Ibrahim, S. A. Shams El-Dine, F. S. G. Soliman, and I. M. Labouta, Pharmazie, 1979,
34. 392.
Thiazolo[5,4- clpyridazines [C3NS-C4Nz]. The reaction between thiazoles and
ArCOCH=CHC02H gives the 2-amino-A2-thiazolines (47), which react with
hydrazine to give the products (134).73*74
Thiazolo[3,2-a]pyrimidines [C3NS-C4N2].The reaction between 2-thiouracil
and ClCH2CH0 gives the thiazolo[3,2-~]pyrimidine(135), whilst 4-thiouracil
gives the isomeric thiazol0[3,2-~]pyrimidine (136) under similar condition^.'^'
A series of thiazol0[3,2-~]pyrimidinescontaining 3-(2-dialkylaminoethyl) sub-
stituents have been prepared from pyrimidine-2-thione and the a-halogenated
ketones XCH2COCH2CH2NR2.163
A re-investigation of the ethylation of 6-ethyl-2,3-dihydrothiazolo[3,2-a]-
pyrimidine-5,7-dione has shown that the product is (137) rather than the pre-
viously reported (138).17*
RHNfr;i.. "" 7 NA-?j

S N
FN'N
5 Jd
(134) (135) ( 1 36)
c13;
0
CA>kt
(137) (138)
Thiazolo-[4,5-d]- and -[5,4-d]-pyrimidines [C3NS-C4Nz].The reaction of the

A4-thiazoline (139) with NaSH or with H2S and pyridine gives the thiazolo-
[4,5-d]pyrimidine-7-thione(140; R' = Ac, R2 = H, X = S),173and with acetic
anhydride and PPA yields (140; R' = H, R2 = Me, X = 0),174 whilst the readily
available ethyl 2-methylmercapto-5-aminothiazole-4-carboxylatewill react with
formamide to give the thiazolo[5,4-d]pyrimidin-4-one(141).'75
Thiazolo[4,5-e]oxazines [C3NS-C4NO].The reaction between the 2-amino-A*-

thiazolines (47) and hydroxylamine gives the thiazolo[4,5-e]oxazines ( 142).73,74
Thiazolo[3,2-a] pyridines [C3NS-C5N]. The condensation between
NCCH=CHCH,CO,Et and 2-aminoethanethiol initially forms a 2-substituted
thiazolidine, which may be cyclized by means of acidic catalysts to the
171
W. I. Krzyzosiak, J. Biernat, J. Ciesiolka, P. Gornicki, and M. Wiewiorowski, Tetrahedron Lett.,
1979,2647.
172 R. A. Glennon, R. G. Bass, and E. Schubert, J. Heterocycl. Chem., 1979, 16, 903.
A. Singh, R. Kumar, and A. S. Uppal, Indian J. Chem., Sect. B., 1979, 17, 7.
174 A. Singh and A. S. Uppal, J. Indian Chem. SOC., 1979, 56, 745.
17' A. K. Sen and G. Chattopadhyay, Indian J. Chem., Sect. B, 1979, 18, 307.
thiazolo[3,2-a]pyridin-5-one ( 143).17(j The reaction between piperidine-2-

thione and methyl diazoacetate gives the S-alkylated product, which cyclizes
immediately to the thiazolo[3,2-a Ipyridin-3-one (144).’77By contrast, piperidin-
2-one reacts to give the N-alkylated product, which does not cyclize.
A novel synthesis of this ring system involves the [4 + 21 cycloaddition of
diphenylketen with 2-styryl-A2-thiazolines, giving compounds (145) in good
~ ~ compound (124; X = CH) also undergoes cycloaddition with
~ i e 1 d s . lThe
acetylenic and olefinic dipolarophiles to give thiazolo[3,2-a]pyridin-5-ones,e.g.
(146)? Thiazolo[3,2-a]pyridinium 3-oxides (147) may be obtained by allowing
pyridine-2(lH)-thione to react with ethyl bromomalonate (R = C02Et)179or
with alkyl bromoacetates (R = H).180 Compound (147; R = H) will undergo
electrophilic substitution at position 2.lgo The thiazolo[3,2-a]pyridinium-8-
olates (148; R = H or Me) rearrange photochemically to the pyridones (149;
R = H or Me) and other isomeric In addition, a product (150),
whose structure was verified by X-ray crystallography, was obtained from (148;
R = Me).182The thiazole ring of (148; R = H) undergoes cleavage on treatment
with strong base to give a mixture of l-vinyl-3-hydroxypyridine-2(1H)- thione
and 2-vinylmercap to-3 -hydroxypyridine. 83
c--:
S
(145)
Ar Me<&ph C0,EtC0,Et
(146)
&--5
(147)
Thiazolo[4,5-blpyridines [C3NS-C5N].The thiazoles (15l),prepared from salts

of cyanimidocarbonic acid and y-bromo-P-keto-esters, may be cyclized under
acidic or basic conditions to give the thiazolo[4,5-b]pyridines ( 152).49350
K. Kubo, N. Ito, Y. Isomura, I. Sozu, H. Homma, and M. Murakami, Yakugaku Zusshi, 1979,99,
880 (Chem. Abstr., 1980, 92, 58 685).
17’ G . Bartels, R. P. Hinze, and D. Wullbrandt, Liebigs A n n . Chem., 1980, 168.
178 M. Sakamoto, K. Miyazawa, K. Kuwabara, and Y. Tomimatsu, Heterocycles, 1979, 12, 231.
179 H. Singh, A. S. Ahuja, and C. S . Gandhi, J. Chem. Res. ( S ) , 1979, 264.
IS’ L. T. Gorb, N. N. Romanov, and A. I . Tolmachev, Khim. Geterotsikl. Soedin., 1979, 1343 (Chem.
Abstr., 1980, 92, 128 789).
T. Laerum and K . Undheim, J. Chem. Soc., Perkin Trans. I, 1979, 1150.
IS’ T. Laerum, T. Ottersen, and K. Undheim, Acta Chem. Scand., Ser. B, 1979, 33, 299.
G. A. Ulsaker, H. Breivik, and K. Undheim, J. Chem. Sac., Perkin Trans. 1 , 1979, 2420.
(153)
Thiazolo[4,5-d]pyrans [C3NS-C50].2-Dimethylamino-thiazoles will undergo
cycloaddition with two moles of t-butylcyanoketen to give a mixture of two
thiazolo[4,5-d]tetrahydropyran-2-ones(153; R' = H or Me, R2 = CN, R3 =
But) and (153; R' = H or Me, R2 = But, R3 = CN); these rearrange thermally,
via open-chain intermediates.lg4
Structures comprising One Five-Membered Ring and One Seven-Membered
.-
Ring ( 5 7 ) Thiazolo- [3,Z-a] - and - [4,5- e]- diazepines [C3NS-C,N, 1.
Thiazolo[3,2-a][ 1,3]diazepines (154) may be obtained from the reaction
between a 1,3-diazepine-2-thione and CY -halogeno-ketones, 163 and the thiazolo-
[4,5-e][ 1,4]diazepines (15 5 ) by the cyclization, under basic conditions, of the
thiazoles (156).Ig5
Structures comprising Two Five-Membered Rings and One Six-Membered Ring

(5,5,6) .-
I,2,4 - Triazolo [3,4- b] benzo thiazole [C2N3- CJVS- C6].The 3 - aryl
derivatives (1 57) were prepared by oxidation of 2-arylhydrazones of benzo-
thiazole, using lead tetra-acetate.'"
Berzzo[Z,.?-d; 5,6-d']bisthiazoles [C3NS-C3NS-C,]. Condensation of chloranil
with ammonium dithiocarbamates gives good yields of the derivatives (158) of
the title
a;;! (157)
Ar
s;$fs<o N
Ar
0
S
(158)
Thiazolo[3,2-a]benzirnidazoles [C3NS-C,N2-C6]. The reaction between
2-amino-thiazoles and p-benzoquinone gives the products (159),188
whilst the
A. Dondoni, A. Medici, C. Venturoli, L. Forlani, and V. Bertolassi, J . Org. Chem., 1980, 45, 621.
K. Hirai, H. Sugimoto, andT. Ishiba, J. Org. Chem., 1980, 45, 253.
D. S. Deshpande, J. Indian Chem. SOC.,1979, 56, 742.
R. P. Soni and J. P. Saxena, J. Indian Chem. SOC.,1979, 56, 733.
18' R. P. Soni and J. P. Saxena, Bull. Chem. SOC.Jpn., 1979, 52, 3096.
condensation of benzimidazole -2-thiol with 1-bromo-2,3 -epoxy-3 -methyl-

butane gives a mixture of the thiazolo- (160) and thiazino-[3,2-a]benzimidazoles
(16 1).'89 The reaction between dimethyl acetylenedicarboxylate (DMAD) and
benzimidazole-2-thiol and certain of its derivatives has been investigated fur-
ther;'90*'91in the presence of base the product is the thiazino-compound (162),
whilst in its absence a mixture of (162) and (163) may be obtained, the latter
rearranging to the former on prolonged heating.'" DMAD reacts with benz-
imidazol-2-ylthioacetonitrile in benzene, THF, or DMF to give the thiazolo-
[3,2-u]benzimidazole (164) as the major product, whereas in aqueous ethanol a
1,3-thiazino[3,2-u lbenzimidazole and a 1,3-thiazepino[3,2-u]benzimidazole
predominate. 19*
lmiduzo [Z, 1-b]benzothiazoles [C3NS-C3N2-C6]. Diphenylketen reacts with the

sulphilimine (165) to give the imidazo[2,1 -b]benzothiazole (166).17'
Thia~olo[3,2-a]indales [C3NS-C4N-C6].Treatment of the indole derivative
(167) with thionyl chloride unexpectedly gave the thiazolo[3,2-a]indol-3(2H)-
one (168), for which a possible mechanism has been ~uggested.'~'
Pyrrolo[2, 1- b]benzothiazoles [C3NS-C4N-C6].Cyclization of the benzo-
thiazolium salts (169) by means of sodium acetate and acetic anhydride gives the
pyrrolo[2,1 -b]benzothiazoles ( 170).'94
0. Hideg-Hankovszky, K. Hideg, and F. Aradis, Acta Chim. Acad. Sci. Hung., 1979, 99, 69.
I9O K. Nagarajan, M. D. Nair, and J . A. Desai, Tetrahedron Lett., 1979, 5 3 .
19' J. J. Wade, J. Org. Chem., 1979, 44, 1816.
19* A. Davidson, I. E. P. Murray, P. N. Preston, and T. J. King, J. Chem. Soc., Perkin Trans. I, 1979,
1239.
L. A. Mitscher and E. W. Hagaman, J. Org. Chem., 1979,44, 3994.
194 I. Ciocoiu, C. H. Budeanu, and I. Zugravescu, Bul. fnst. Politeh. I&, Sect. 2, 1978, 24, 109 (Chem.
Abstr, 1980, 92, 41 819).
R20C
,-COR'
L M e
Structures comprising Two Five-Membered Rings and One Seven-Membered

Ring (5,5,7).-Azu/eno[2, I-dlthiazoles [C3NS-C5-C7]. The reaction between
the substituted azulenes (171; R = H or C0,Et) and neutral or basic alumina
gives the title compounds (172).195
4-Ata-azuleno[2,3-d]thiazoles [C3NS-C4N-C7].The reaction between 3-
thiocyanato-2-amino- 1-aza-azulene and acetic anhydride gives (173; R = Ac),
which can be hydrolysed to (173; R = H).195
SCN
Structures comprising One Five-Membered Ring and Two Six-Membered

Rings (5,6,6).-1,3,5-Triatino [Z, 1 - blbenzothiazole [C3NS-C3N3-C6].
2-Amino-
benzothiazole reacts with PhCCl=NCH,Cl to give the 1,3,5-triazino-
[2,1-b]benzothiazole (174). lg6
S-Thia-1,4-diazacycl[3.3.2~uzi~es [C3NS-C4Nz-C4Nz].The condensation
between ethyl 4-chloroacetoacetate and 4-amino-6-hydroxypyrimidine-6-thiol
gave the covalently hydrated cyclazine (175), and not the isomeric (176).'97
0 0
K. Yamane, K. Fujirnori, N. Hirako, S. Ichikawa, and S. Miyoshi, Koen Yushishu-Hibenzenkei

Hokozoku Kagaku Twonkai [Oyobi] Kozu Yuki Kagaku Toronkai, 12th, 1979,45 (Chem. Abstr.,
1980,92, 181 069).
H. Boehme and H. J. Drechsler, Arch. Pharm. (Weinheim, Ger.),1979,312, 1011.
E. Campaigne, J . C . Huffman, and T. P. Selby, J. Heterocycl. Chem., 1979, 16, 725.
Thiazolo [5,4 -b]naphthyridines [C3NS-C5N-C5N].The reaction of 6-amino-
l-ethyl-7-mercapto-1,4-dihydro-4-oxonaphthyridine-3-carboxylic acid with
acid anhydrides or acid chlorides and ethyl xanthate yields the title
compounds (177).It is also possible to obtain this ring system in one step, starting
from ethyl 7-chloro-l-ethyl-6-nitro-1,4-dihydro-4-oxonaphthyridine-3-
carboxylate and potassium thiocyanate in acetic acid. 19*
Pyrirnido[2,1- b]henzothiazoles [C3NS-CJV2-C6]. The reaction between 2-
aminobenzothiazole and dimethyl 2-aminofumarate gives the 4-
oxopyrimido[2,1-b]benzothiazole derivative (178), whereas with DMAD the
isomeric 2-oxo-compound (179) is ~ b t a i n e d .The
' ~ ~ring system (178) may also be
obtained starting from diethyl ethoxymethylenemalonate,'99 or from ethoxy-
methylenemalononitrile.200
Et
(177) (178) (179)
Thiazolo-[2,3- b]-, -[3,2-a]-, a n d - [3,2- c]-quinazolines [C3NS-C,N2-C6].

Thiazolo[2,3-b]quinazolines (180)may be obtained by the cyclocondensation of
ethyl anthranilate with SCNCH,C_CCH,NR,, followed by treatment with
Cyclodehydration of the quinazolines ( l S l ) , using acetic anhydride and
pyridine, gives the meso-ionic thiazolo[3,2-a]quinazolones (182), which undergo
nucleophilic attack by ethanol or methanol to give the adducts (183; X = Et or
Me),," and the reaction between quinazoline-4(3H)-thione and ethyl
bromomalonate gives the meso-ionic thiazolo[3,2-c]quinazoline ( 184).'79
'" N. Suzuki and R. Dohmori, Chem. Pharm. Bull., 1979, 27, 410.
199 J. J. Wade, R. F. Hegel, and C. B. Toso, J. Org. Chem., 1979,44, 1811.
2oo R. R. Covington, D. L. Temple, and J. P. Yevich, Ger. Offen. 2 918 085/1979 (Chem. Abstr. 1980,
92, 163 993).
201 G . Ferrand, Fr. Demande 2 393 001/1978 (Chem. Abstr., 1979, 91, 175 390).
202 P. B. Talukdar and S. K. Datta, Indian J. Cham., Sect. B,1979, 18, 39.
Pyrido [Z,I - b]benzothiazoles [C3NS-C5N-C6]. The condensation between

NCCH=CHCH,CO,Et and o-aminothiophenol gives a benzothiazoline, which
cyclizes in acid to the pyrido[2,1-b]benzothiazole (185; R = H).176 The
Vilsmeier reaction on ethyl benzothiazole-2-acetate gives an enamine (log),
which reacts with diketen, acetic anhydride, NCCH2C02Et, etc. to give, e.g.,
(185; R = C02Et).14"The pyridine ring of (185; R = OH) may be cleaved by
amines at ca 140°C to give (186),'03 but the ring is stable to this treatment in
(185; R = OAc).
~' N ~sc H 2 c o C H , c o N H K
(185) (186) (187)

Thiazolo[3,Z-a]quinolines[c3Ns-cSN-c6]. Quinoline-2-mercaptoacetic acid
undergoes cyclocondensation with acetic anhydride to form the meso-ionic
compound (187; R = Ac); by modifying the conditions, [187; R =
COCH2S-(2-quinolyl)]may be obtained
Thiazolo[Z,3-a]isoquinolines [c,"-C,N-c6]. Isoquinoline-l(2H)-thione
reacts with ethyl bromomalonate to give the meso-ionic thiazolo[2,3-a]isoquino-
line ( 188),i79whilst 3,4-dihydroisoquinoline-l(2H)-thione reacts with ethylene
dibromide to give the salt (189; X = Br)205or with ally1 bromide, followed by
treatment with PPA, to give (189; X = C104),'06 both of these salts being
reducible to the 2,3,5,6-tetrahydro-compoundby using sodium borohydride.
Other Condensed Systems incorporating Thiazole. The reaction between 2-

amino-A2-thiazoline and toluene-3,4-bis(sulphonyl chloride) gives the
thiazolo[2,3 -f]benzo[b]- 1,4-dithia-S ,7-diazepine ( 190).207 2-Chlorobenzo-
thiazole reacts with various nitroanthranilic acid chlorides to give the benzo-
thiazolo[2,l-b]quinazolines ( 191).'08 Condensation of naphtho[l,2-d]-
thiazole with acetylenic esters gives the naphtho[l,2-d]thiazolo[3,2-a]-
pyrimidines ( 192),209 whilst 1H-perimidine-2-thiol reacts with methyl
chloroacetate to give the lH-perimido[2,1-b]thiazole (193)210 and with
a-halogenated ketones to give similar products.211
203 M . I. Ali and H. A . Hammouda, J. Prakt. Chem., lY79,321, 331.
204 L. T. Gorb, N . N. Rornanov, and A . I. Tolrnachev, Khim. Geterotsikl. Soedin., 1979, 989 (Chem.
Abstr., 1979, 91, 211 314).
'05 H. Singh, K. B. Lal, and S. C. Malhotra, Indian J. Chenz., Sect. B,1979, 17, 4.
'06 H. Singh and M. S. Bal, Indian J. Chem., Sect. B, 1979, 18, 312.
207 V. P. Arya, Indian J. Pharm. Sci., 1979, 41, 42, (Chem. Abstr., 1979, 91, 20 466).
208 G. Wagner and E. Bunk, Pharmazie, 1979,34, 138.
'09 K.-C. Liu, S.-Y. Chow, T.-M. Tao, and L.-C. Lee, Arch. Pharm. (Weinherm, Ger.), 1979, 312,619.
'lo K.-C. Liu, H.-H. Chen, L.-C. Lee, and J.-W. Chern, Arch. Pharm. ( Weinheim, Ger.), 1979,312,776.
*" V. K. Gupta, M. L. Sachdeva, K. S. Dhaka, V. K . Chadha, and H. K. Pujari, A n n . SOC.Sci., Bruxelles,
Ser. 1, 1979, 93, 137 (Chem. Abstr., 1980, 92, 198 369).
(193)
(191)
15 Thiadiazoles and Selenadiazoles

1,2,3-ThiadiazoIes.-Synthesis. The reaction between the hydrazones
R’CH2CR2-NNHR3 (R’, R’ = H or aryl, R3 = Ac or tosyl) and thionyl
chloride gives the 1,2,3-thiadiazoles (194), but cyclization does not occur with
sulphuryl chloride.’12 Methyl or phenyl isothiocyanates react with acyl-
diazomethanes to give good yields of 5-(acylamino)-1,2,3-thiadiazoles[ 194;
R’ = MeCONH or PhCONH; R2 = CO,Et, COPh, or P(0)R3R4].213 The un-
stable A2-1,2,3-thiadiazoline (199, which eliminates nitrogen to give the thiiran
(196), is obtained in the cycloaddition reaction between Ph2CNz and the
cyanothioformamide NCC(,S)NPhAc. Similar reactions yield 1,3,4-thiadiazol-
ines and 1,3,5-oxathiazolines (see later).214Meso-ionic 1,2,3-thiadiazoles (197;
R’ = Me or Ph; R’ = H, Me, or Ph; X = 0; Z = S) are obtained from the
sydnones (197; same R’and R’; X = Z = 0)by successive treatment with the
Meerwein reagent, sodium hydrosulphide, and ethanolic ammonia. Further
alkylation and reaction with NaHS gives (197; same R’ and R2; X = Z = S).’I5
Ph . _. R’
Chemical Properties of 1,2,3-Thiadinzoles. Experiments on the photolysis of

lY2,3-thiadiazoles(194; R’, R’ = ‘H, 2H),using Fourier-transform i.r. spectros-
copy,216and on [194; R’R’ = (CH2),,; n = 4-61, to give a mixture of 1,4-
dithiins, thiophens, 1,3-dithioles, and 1,2,4,5-tetrathione~,~’’ have been re-
ported. Flash thermolysis of a series of 1,2,3-thiadiazoles (194; R’, R2 = alkyl,
phenyl, C1, or CN) gave the corresponding thioketens R’R2C=C=S.
Irregularities in the migratory aptitudes of the substituents in the Wolff -type
rearrangement of the primary fragments indicate that thiirans participate in the
formation of the thioketens.’’* Thermolysis in diethylene glycol, giving a variety
212 H. Meier, G. Trickes, E. Laping, and U. Merkle, Chern. Ber., 1980, 113, 183.
’13 M. Regitz, B. Weber, and A. Heydt, Liebigs A n n . Chern., 1980, 305.
K. Friedrich and M. Zamkane, Chern. Ber., 1979, 112, 1873.
2’s K. Masuda. J. Adachi, and K. Nomura, J. Chern. SOC.,Perkin Trans. 1, 1979, 956.
’16 M. Torres, I. Safanik, A. Clement, J. E. Beatie, and 0. P. Strausz, Nouv. J. Chim., 1979, 3, 365
(Chern. Absrr., 1979, 91, 139 906).
*” H. Buehl, U. Timm, and H. Meier, Chern. Ber., 1979, 112, 3728.
’18 E. Schaurnann. J. Ehlers, and H. Mrotzek, Liebigs Ann. Chern.. 1979, 1734.
of and of benzo-l,2,3-thiadiazole in tetrahydronaphthalenezz2

have also been described. 5-(Alkylthio)-1,2,3-triazoles(198; R3 = Me or Et,
R4 = alkyl) have been obtained from a thermal rearrangement of the compounds
(194; R' = NR4C02R3, R2 = H),223and various 5-substituted derivatives of
meso-ionic 1,2,3-thiadiazolium-4-01ate (199), obtained by standard procedures,
have been
(198) ( 1 99) (200) O (201)
Benzo-1,2,3-thiadiazole reacts with phenyl isothiocyanate to give the 2-

phenylimino-l,3-benzodithiole(200), which was not isolated but converted into
the quaternary ammonium salt with methyl iodide.225A series of 4,6-dialkyl-
1,2,3-thiadiazo10[4,5-d]pyrimidine-5,7-diones(201) has been prepared from the
reactions of 6-hydrazino-uracils either with alkyl thiocyanates (to give the
thiosemicarbazides, which cyclized on treatment with bromine) or with thionyl
chloride.226
1,2,3-Selenadiazoles.-The reaction of the semicarbazone PhCH=CHCMe=
NNHCONHz with selenium dioxide gives the 4-vinyl-l,2,3-selenadiazole(202;
R = PhCH=CH),227 and a similar reaction between PhCOCMe2CMe=
NNHCONH2 and H275Se03 gives the labelled compound (202;
R = PhCOMe2), which is a potential adrenal-imaging agent.228 Ther-
molyses of the 1,2,3-~elenadiazoles(202; R = H, Me, or But) yield the
selenoketens; these have been isolated at -196 "C, but they dimerize with loss of
nitrogen at higher temperature^.^^^'^^^
1,2,4-Thiadiazoles.-Synthesis. The reaction between benzoyl isothiocyanate
and alkyl azides RN3 gives a mixture of the 1,2,4-thiadiazole (203; R' =
NRCOPh, R2 = SCOPh) and the 1,2,4-dithiazole (204).231 The oxidation of the
aryl thioamides ArCSNH2 with nitrous acid gives a mixture of (203; R' = R2 =
Ar) and ArCN, but, when Ar was 2,6-dichlorophenyl, the aryl isothiocyanate was
isolated.232Oxidation of the substituted amidines, e.g. PhC(S)N=CPhNHPr,
219 E. Schaumann, J. Ehlers, W. R. Foerster, and G . Adiwidjaja, Chem. Ber., 1979, 112, 1769.
U. Timm and H. Meier, J. Heterocycl. Chem., 1979, 16. 1295.
221 H. Meier, S. Graw, U. Timm, and T. Echter, Nouu. J. Chim., 1979,3,715 (Chem.Abstr., 1980,92,
163 911).
222 R. C. White, J. Scoby, and T. D. Roberts, Tetrahedron Lett., 1979, 2785.
223 K. Masuda, Y . Arai, and M. Itoh, Synthesis. 1979,470.
224 K. Masuda, J. Adachi, and K . Nomura, J. Chem. Soc., Perkin Trans. 1, 1979, 2349.
225 P. W. Sprague and J. E. Heikes, Synthesis, 1979,297.
226 T. Naka and Y. Furukawa, Chem. Pharm. Bull., 1979,27,1965.
227 I. Lalezari, A. Shafiee, and S. Sadeghi-Milani, J. Hererocycl. Chem., 1979, 16, 1405.
228 R. N. Hanson and M. A . Davis, J. Labelled Compd. Radiopharm., 1979,16,31 (Chem.Abstr., 1980,
92, 22 436).
229 A . Holm, C. Berg, C . Bjerre, B. Bak, and H. Svanholt, J. Chem. Soc., Chem. Commun., 1979,99.
230 R. Schulz and A. Schweig, Angew. Chem., Znt. Ed. Engl., 1980, 19, 69.
231 G . L'abbC, M. Komatsu, C. Martens, S. Toppet, J . P. Declercq, G. Germain, and M. Van Meerssche,
Bull. Soc. Chim. Belg., 1979, 88, 245.
232 M. Bahadir, S. Nitz, H. Parlar, and F. Korte, 2. Nufurforsch., Ted B, 1979, 34, 768.
using hydrogen peroxide in acetic acid, gives the 2-alkyl-3,5-diaryl-l,2,4-thiadi-

azolium salts, e.g. (205).233Imidoyl-thioureas R'N=CPhNHCSNHR2 can be
cyclized to the unstable A3- 1,2,4-thiadiazolines (206); these rearrange thermally
to the 1,2,4-thiadiazoIidines (207), also obtained by treatment of the carbodi-
irnide R2N=CPhN=C=NR' with 5-Amino-1,2,3,4-thiatriazoles
can be converted into 3-0x0-A4-1,2,4-thiadiazolin-5-yl-ureas(208) by heating
with alkyl i ~ o c y a n a t e s whilst
, ~ ~ ~ 2-alkoxycarbonyl-3-imino-5-methylrnercapto-
A4- 1,2,4-thiadiazolines are readily obtained from N- chloro-carbamates and
cyanoiminodithi~carbamates.~~~ Oxidation of 1-alkyl-3-aryl-thioureas with
benzoyl peroxide gives a mixture of 1,2,4-thiadiazolidines (209; R' = R2 = Ar,
R3 = R4 = alkyl), (209; R' = R4 = alkyl, R2 = R3 = Ar), and (209; R' =
R3 = alkyl, R2 = R4 = Ar).237The so-called 'isothiocyanate oxides' of Types A
and B may be obtained by oxidation of alkyl isothiocyanates, using various
nitrones, and they are 1,2,4-dithiazolidine-3-ones and 1,2,4-thiadiazolidin-5-
one-2-thiones, respectively.238The syntheses of various bicyclic 1,2,4-thiadi-
azoles, e.g. (210), (21l ) , and (212), have been de~cribed.~"
N R ~
R~ N L>R'
Ph
RA
R2N =PhCN Tph=NR2
1NS / N R 1
2 Asp'
J+Y"'
R 3 N 4
H2NCON R4N
R'
(206) (207) (208) (209)
N R ~
Properties of 1,2,4-Thiadiazo~es. Proton n.m.r. spectroscopy of the products of

the condensation of S-amino-3-methyl-1,2,4-thiadiazole with nitriles RCN shows
that they consist of an equilibrium mixture of (213a) and (213b), which does not
occur with the corresponding 1,2,4-0xadiazoles.~~~) The structure of the product
(214; X = 0) obtained by the reaction of Hector's Base (214; X = NH) with
mineral acid has been elucidated by means of X-ray cry~tallography.~~' An
233 J. Liebscher, Ger. (East) P. 136 965/1979 (Chem. Abstr., 1980, 92,58 789).
234 J. Goerdeler, J. Haag, and W. Loebach, Chem. Ber.. 1979, 112,1288.
235 G. Kaugers and V. L. Rizzo, J. Org. Chem., 1979, 44, 3840.
236 T. Fuchigarni and T. Nonaka, Chem. Lett., 1979, 829.
237
T. Kinoshita, S. Sato, and C . Tarnura, Bull. Chem. SOC.Jpn., 1979, 52, 1225.
238 E. Eghtessad and G. Zinner, Arch. Pharm. (Weinheim, Ger.), 1979, 312, 1027; G. Zinner and E.
Eghtessad, Dtch. Apoth-Ztg., 1979, 119,203 (Chem. Abstr., 1979 91,20 352).
23y J. 0. Gardner and C. C. Beard, J. Pharm. Sci., 1979,68, 182.
24" K . Akiba, T. Kobayashi, and S. Arai, J. A m . Chem. SOC.,1979, 101, 5857.
241 A. F. Cuthbertson, C. Glidewell, H. D. Holden, and D. C. Liles, J. Chem. Res. ( S ) , 1979, 316.
NHPh
M e c N \ y N y Me yNyN
R]
N-S NH, H,N S-N
(213a) (213b)
investigation of the effect of electrophilic reagents on 3-hydroxy-5 -substituted-

1,2,4-thiadiazoIes shows that hard electrophiles react at the O H group whilst soft
electrophiles substitute on N-2.242
1,3,4-Thiadiazoles.-Synthesis. The thiosemicarbazides ArNHC(S)NHNH-
COCH2CN react with acetyl chloride to give a mixture of the 1,3,4-thiadiazole
(215) and a t r i a z ~ l e t h i o l .Methyl
~ ~ ~ 3-acetyldithiocarbazate reacts with either
POCI, or PSCI3 and NEt, to give 2-methyl-5-methylmercapto-l,3,4-thiadiazole,
whereas a phosphorus-containing heterocycle is obtained with PC13 (see
Tetramethyldithiocarbamidium iodide, Me2NC(SMe)2' I-, reacts with thio-
semicarbazide to give 2-amino-5 -dimethylamino- 1,3,4-thiadiazole in good
yield.245 The reaction between aryl-dibromodiazabutadienes
ArCH=N-N=CBr2 and thioacyl-hydrazines ArC(S)NMeNH2gives the 1,3,4-
thiadiazolinium bromides (216), which react with ammonia to give the meso-ionic
compounds (217). These compounds rearrange in aqueous ethanolic ammonia to
the triazolinium thiolates (218).24"
N-N MA-N Br-
AcRNJ!, >CH,CONHAC A r c >NHN=CHAr
S 5
(215) (2 16)
Ar NN=CHAr
(2 17) (2 18)
The reaction between thiosemicarbazones and acetic anhydride, which had
been assumed previously to give NS-diacyl derivatives, has now been shown to
give the 4-acetyl-2-acetylamino-A2-1,3,4-thiadiazoline(219; R' = NCCOMe,
R2 = COMe, R3 = Ph, R4 = H),247 and the structure of the condensation
product of benzoyl isothiocyanate and benzaldehyde phenylhydrazone has been
shown, using X-ray crystallography, to be (220; R' = R2 = Ph, R3 = COPh).248
The thiocyanate (MeCO),CHSCN reacts with arenediazonium salts to give the
thiadiazolines (220; R' = COMe, R2 = Ar, R3 = H), probably formed via a
242
L. Taliani and J. Perronnet, J. Heterocycl. Chern., 1979, 16, 961.
243
L. Proinov, C. Ban, M. Topirceanu, and D . Diaconescu, Farrnacia (Bucharest), 1979, 27, 167
(Chem. Abstr., 1980, 92, 163 906).
244
N. I. Shvetsov-Shilovskii, D. P. Nesterenko, and A. A. Stepanova, Zh. Obshch. Khim., 1979, 49,
1896 (Chem. Abstr., 1980, 92, 41 846).
245
S . A. Okecha, Chem. Ind. (London), 1979,526.
246
E. Cawkill, W. D. Oilis, C. A. Ramsden, and G. P. Rowson, J. Chem. Soc., Perkin Trans. 1,1979,
724.
247
S . Kubota, Y. Ueda, K. Fujikane, K. Toyooka, and M. Shibuya, J. Org. Chem., 1980,45, 1473.
248
Y. Fukutani, K. Tsukihara, Y . Okuda, K. Fukuyama, Y. Katsube, I. Yamamoto, and H. Gotoh, Bull.
Chem. SOC. Jpn., 1979, 52, 2223.
Japp-Klingemann reaction followed by c y ~ l i z a t i o n ;similar
~ ~ ~ products (220;
R’ = CHMeR, R2 = Ar, R3 = H) are obtained by the reaction of the hy-
drazonoyl bromides MeCHRC(=NNHAr)Br (R = H or Me) with potassium
t h i o ~ y a n a t e .The
~ ~ ~phenylhydrazone
’ derivative PhCCl=NNHPh reacts with the
cyanothioformamide NCC(S)NPhBz to give the A2-1,3,4-thiadiazoline (2 19;
R’ = R2 = Ph, R3 = CN, R4 = NPhBz),*14and the amidino-1,3,4-thiadiazoline
[219; R’ = R3 = Ph, R2 = C(=NH)NH,, R4 = HI was a rather surprising
product of the interaction between the chlorodiazabutadiene
PhCCl=NN=CHPh and thiourea, for which a possible mechanism has been
de~cribed.’~’ Photolysis of a mixture of the sulphinyl-pyrazolenine (22 1) and
2-diazopropane gives a low yield of the A3-173,4-thiadiazoline1-oxide (222). The
reaction probably involves formation of a sulphinylvinylcarbene, which then
cvclizes with the d i a ~ ~ - ~ ~ m p ~ ~ n d . ~ ’ ~
Properties of 1,3,4-Thiadiazoles. The ring-chain tautomerism of various N-

methylated ac&tone thiosemicarbazones-l,3,4-thiazolidines has been investi-
gated, using ‘H n.m.r. The kinetics of the reaction between
5 -phenyl-l,3,4-thiadiazole-2-diazonium salts and water, which shows general
acid-base catalysis, has been i n v e ~ t i g a t e dThe
. ~ ~ ~reaction between l-methyl-
adamantane-2-thione and But2CN2gives the strongly sterically hindered A3-
1,3,4-thiadiazoline (223), which rearranges to the 2,5-di-adamantyl deriva-
ti~e.~~’
Condensed 1,3,4-Thiadiazoles.-The reaction between the triazolium-3 -thiolate
(224) and cyanogen bromide gives the s- triazolo[3,4-b]- 1,3,4-thiadiazolium salt
(225), and (224) forms the meso-ionic triazolo[3,4-b]-1,3,4-thiadiazolium-2-
olate (226) with phosgene.256The 5-aryl-1,2,3,4-tetrazoleswill react with thio-
phosgene to give the s- triazolo[3,4-b]- 1,3,4-thiadiazoles (227),257whilst 2,3-
(224)
249
N. F. Eweiss and A. Osman, Tetrahedron Lett., 1979, 1169.
2x1
A . S. Shawali, H. M. Hassaneen, and N. F. Eweiss, J. Appl. Chem. Biotechnol., 1978,28,864 (Chern.
Abstr., 1980, 92, 5999).
25 1
W. T. Flowers, S. F. Moss, J. F. Robinson, D. R. Taylor, A. E. Tipping, and M. J. Haley, J. Chem.
Soc., Chem. Commun., 1979, 149.
252
M. Franck-Neumann and J. J. Lohmann, Tetrahedron Lett., 1979, 2397.
253
M. Uda and S. Kubota, J. Heterocycl. Chern., 1979, 16, 1273.
254
J. Kavalek, K. Janak, and V. Sterber, Collect. Czech. Chern. Commun., 1979, 44, 3102.
255
F. Cordt, R. M. Frank, and D. Lenoir, Tetrahedron Lett., 1979, 505.
256
K. Masuda, J. Adachi, T. Shibata, and K. Nomura, Chern. Pharm. Bull., 1979,27, 1688.
257
T. Resetova, Zb. Stud. Ued. Odb. Pr. (Slov. Vys. Sk. Tech. Bratislave, Chernickotechnol. Fak.), 1979,
19 (Chem. Abstr., 1980,92, 128 822).
diamino-1,3,4-thiadiazoliumsalts will react with acyl halides to give the sym-

triazolo[3,2-6]- 1,3,4- thiadiazoles (228).2s8Variously substituted imidazo[2,1-
b ] -1,3,4-thiadiazoles (229) have been obtained by allowing substituted 2-amino-
1,3,4-thiadiazoles to react with phenacyl halide^.'^^-*^^ S-Methy1-1,3,4-thiadi-
azole-2(3H)-thione reacts with PhCHBrCOCl to give anhydro-5-hydroxy-2-
methyl-6-phenylthiazolo[2,3-b]-1,3,4-thiadiazolium hydroxide; this reacts with
acetylenic and olefinic dipolarophiles, with cleavage oi the thiazole ring, to give
1,3,4-thiadiazolo[3,2-a]pyridin-5-ones, e.g. (230)."* The U.V.absorption spectra
of some new 6-hydroxy-l,3,4-thiadiazolo[2,3-b]benzimidazoles, formed by the
reaction between 2-amino-l,3,4-thiadiazoles and p - benzoquinone, have been
determined, and they show bathochromic shifts in both acidic and basic media,
owing to the dipolar nature of the molecules.262The condensation of 2-halogeno-
1,3,4-thiadiazoles with anthranilic acids yields the 173,4-thiadiazolo[2,3-b]-
quinazolin-5-ones (231).263A novel phototransformation of the meso-ionic
1,3,4-thiadiazolo[2,3-a]isoquinoline(232) in ethanol is shown in Scheme 7. 264
a\
N HCO ,E t
t-
EtOH &
\
N=C=O
Scheme 7
2s8 Y. Tamura, H . Hayashi, J.-H. Kim, and M. Ikeda, Chem. Pharm. Bull., 1979,27, 2521.
2s9 M. A. Eldawy, S. A. Shams El-Dine, and K . M. El-Brembaly, Pharmazie, 1979,34, 144.
260 K. C. Joshi, V. N. Pathak, and P. Panwar, J. Indian Chem. SOC.,1979, 56, 716.
261 H. Horstmann, K. Meng, F. Senter, and E. Moeller, Ger. Offen. 2 823 686/1979 (Chem. Abstr.,
1980,92, 215 440).
262 R. P. Soni and J. P. Saxena, Bull. Chem. SOC.Jpn., 1979, 52, 2033.
F. Russo, M. Santagati, and A. Santagati, Farmaco, E d . Sci., 1979,34,688(Chem.Abstr., 1979,91,
193 251).
264
M. Lempert-Streter and K . Lempert, J. Chem. Res. ( S ) , 1979, 377.
1,2,5-Thiadiazoles.-Synthesis. The reaction between thiazyl fluoride
( N 3 - F ) and hexafluorobut-2-yne gives a mixture of 3,4-bis(trifluoromethyl)-
1,2,5-thiadiazole (233; R' = R2 = CF3) and the dithiadiazole (234).26s3,4-
Disubstituted-l,2,5-thiadiazolesmay also be obtained in the reactions between
sulphur nitride (S4N4)and ketones R'CH2COR2(R' = Ar; R2 = Me, benzyl, or
Ph)266or acetylenes R'C=CR2 (R', R2 = C02Me, b e n ~ y l ) ; in ~ ' the
~ latter case,
lesser amounts of 1,2,3- and 1,2-4-thiadiazoles are also obtained. The meso-ionic
1,2,5-thiadiazolium-4-olates (235) can be obtained by sequential treatment of
the a-amino-amides ArCH(NHR)CONH, with sulphur chloride and tri-
ethylamine,268whilst base-catalysed (e.g. NaH and A c 2 0 ) cyclization of the
propynyl-sulphonamide (HC-CCMe2NH)2S02 gives the 1,2,5-thiadiazol-
idine 1 , l-dioxide (236); this undergoes an amino-Claisen rearrangement to
give (237), the structure of which was obtained by X-ray crystallography.26'
Reactions of 1,2,5-Thiadiazoles.The 2-methyl-3-methylamino-1,2,5-thiadi-

azolium salt (13; X = N) undergoes ring-expansion on treatment with cyanide
ion to give (14; Z = NH) and with MeO,CC=C- to give (14; Z = CHC0,Me);
see Scheme l.,'
2,1,3-Benzothiadiazoles.-Benzene-1,2-bis-sulphonamides will react with
2-oxides (238; R =
thionyl chloride to give 1,3-ditosyl-2,1,3-benzothiadiazole
H, Me, or NO,; X = N T O S ) , whereas
~ ~ ~ ) 3-bromo-4,5-diaminotoluene reacts with
the same reagent to give the 2,1,3-benzothiadiazole (239).271
Condensed 1,2,5-Thiadiazoles.-5-Brorno-2,3-diaminopyridine reacts with
thionyl chloride to give 1,2,5-thiadiazol0[3,4-b]pyridine (240; R = Br); this
reacts with cuprous cyanide to give (240; R = CN), but with morpholine it gives
(241), presumably uia an intermediate ~ y r i d y n e .1,2,5-Thiadiazolo[3,4-c]-
~~~
26s W. Bludssus a n d R. Mews, J. Chem. SOC.,Chern. Cornmun., 1979,35.
266
S. Mataka, A. Hosoki, K. Takahashi, and M. Tashiro, Synthesis, 1979, 524.
267 S. Mataka, K. Takahashi, Y. Yarnada, and M. Tashiro, J. Heterocycl. Chem., 1979, 16, 1009.
268 K. Masuda, J. Adachi, and K. Nomura, J. Chern. SOC.,Chem. Cornrnun., 1979, 331.
269 R. J. Baker, S.-K. Chiu, C . Klein, J . W. Timberlake, L. M. Trefonas, and R. Majeste, J. Org. Chem.,
1980, 45, 482.
270
L. Capuano, G. Urhahn, and A. Willmes, Chern. Ber., 1979, 112, 1012.
271 K. S. Sharma, V. Singh, and R. P. Singh, Indian J. Chem., Sect. B, 1978, 16, 892.
272
K . S . Sharma, R. P. Singh, and V. Singh, Indian J. Chern., Sect. B, 1979, 17, 13.
pyridines (242) may be conveniently obtained by allowing 3,4-diaryl-1,2,5-

thiadiazoles to react with amines RCH2NH2in the presence of DBU.273The
indeno[2,3-c]- 1,2,5-thiadiazole (243; X = 0)has been obtained from the reac-
tion between indan-1-one or indane-l,2-dione and sulphur nitride,274and the
diazo-derivative (243; X = N2) reacts with DMAD to give [243; X =
C(C02Me)C(=N2)C02Me].275
2,1,3-Benzoselenadiazoles.-Equilibrium and rate constants have been deter-
mined for the reaction between 0-phenylenediamines and selenous acid, H2Se0,,
which gives the 2,1,3-benzoselenadiazoles(244),276whose acidity constants have
been measured spectrophotometrica11y.277 Flash photolysis of 2,1,3-benzo-
selenadiazole 2-oxide gives a transient species (245) together with (244; R' =
R2 = H), whilst photolysis in the presence of selenium atoms gives (246).
Thermolysis of 2,1,3-benzoselenadiazole 2-oxide gives 2,1,3-benzoxadiazole
and selenium.278Thiadiazoles containing 'hypervalent' sulphur are covered in
Part I11 of this chapter, under trithiapentalenes.
N=Se N=Se=Se
16 Dithiazoles and Diselenazoles

1,2,3-Dithiazoles.-l,2,3-Benzodithiazolium chloride (247; X = Y = S),
obtained from the reaction between aromatic amines and disulphur dichloride (cf.
Vol. 1, p. 163), is hydrolysed in aqueous sodium hydroxide to the 2-amino-
thiophenoi, via the 1,2,3-benzothiazolium It is also possible to
isolate the 2-oxide (248; X = Y = S, Z = 0),using aqueous sodium carbonate;
the selenathiadiazolium salt (247; X = Se, Y = S) yields an analogous product
(248; X = Se, Y = S, Z = 0),whilst the isomer (247; X = S, Y = Se) is
converted into the diselenide (249).28"2-Aminonaphthalene-1-sulphonic acid
273 S. Mataka, K. Takahashi, and M. Tashiro, Synthesis, 1979, 687.
274 M . Tashiro and S. Mataka, Jpn. Kokai Tokkyo Koho 79 132 572 (Chem. Abstr., 1980,92,111 022).
275 S. Mataka, K . Takahashi, and M. Tashiro, Chem. Lett., 1979, 1033.
276 J . Neve and M. Hanocq, Tuluntu, 1979, 26, 1173.
277 J. Neve, M. Hanocq, and L. Molle, Tuhntu, 1979, 26, 15.
"'C. L. Pedersen, Tetrahedron Lett., 1979, 745.
279 N. K. Goswami, S. K. Jain, and R. R. Gupta, Chem. Znd. (London), 1979,349.
280 B. K. Strelets, M. M. Gel'mont, Yu. I. Akulin, and L. S. Efros, Khim. Geterotsikl. Soedin., 1979,1205
IChem. Abstr., 1980,92, 128 024).
(Tobias acid) reacts with disulphur dichloride to give the 1,2,3-naphthodithi-

azolium salt (250), which has been converted into other heterocycles; e.g., (250)
with chloroacetic acid gives (251).2R'
The reaction between the sterically hindered
aniline (252; R = Me) and disulphur dichloride gives the stable product (253;
R = Me) whereas (252; R = Bu') gives an equilibrium mixture of (253; R =
Bu') and (254),282with the latter as the major component. This equilibrium has
been investigated, using 'H n.m.r. spectroscopy,28' and the reaction of the
mixture with rn-chloroperoxybenzoic acid gives the 1-oxide of (254) together
with (255).284
\ Y
(247) (248) (249)
Bu' H
B u' (255)
(253)
(254)
Oxidative debenzylation of the thiourea derivative
PhCH2SCHPh=NC(S)NHAr, using bromine and chloroform, gives the 3-aryl-
imino-5-phenyl-l,2,4-dithiazoles (256).2851,2,4-Dithiazolium salts (257) react
with aqueous ethanolic triethylamine to give monothiodiaroylamines
ArC(S)NHCOAr,286and with secondary amines to give the corresponding ami-
dines ArC(S)N=CArNR*R2.287The synthesis of 3,5-diaroylimino-1,2,4-dithi-
azolidines (204)23' was described earlier (p. 1351, and similar compounds are
obtained by allowing RCOCH2C(S)NHAr to react with bromine.288 3,5-Di-
imino-1,2,4-dithiazolidines(258) are also formed when the A4-thiazolines (259)
are treated with PPA.'73
The 1,2,4-dithiazolidines (260; n = 0 or 1) are obtained when the
compounds (261; n = 0 or 1) react with carbon d i s ~ l p h i d e . ~ ~ ~
**' B . Hirsch and D. Albrecht, Ger (East) P. 138 207/1979 (Chem. Abstr., 1980,92, 128 934).
282 Y. Inagaki, R. Okazaki, and N. Inamoto, Bull. Chem. SOC.Jpn., 1979, 52, 1998.
283 Y. Inagaki, R. Okazaki, N. Inamoto, K. Yamada, and H. Kawazura, Bull. Chem. SOC.Jpn., 1979,52,
2008.
284 Y. Inagaki, R. Okazaki, and N. Inamoto, Bull. Chem. SOC. Jpn., 1979,52,3615.
2R5 R. Rai and V. K . Verma, Indian J. Chem., Sect. B, 1979, 18, 284.
286 J. Liebscher and H. Hartmann, Ger. (East) P. 135 901/1979 (Chem. Absfr., 1979, 91, 193 019).
287 J. Liebscher and H. Hartmann, Ger. (East) P. 130 245/1978 (Chem. Abstr., 1979, 91, 39 161).
A. N. Borisevich and P. S . Pel'kis, Khim. Geterotsikl. Soedin., 1979, 1479 (Chem. Abstr., 1980,92,
94 319).
289 R. J . S. Beer, N. H. Holmes, and A. Naylor, J. Chem. SOC.,Perkin Trans. I, 1979, 2909.
(256) (257) (258)
1,2,4-Diselenazoles.-1,2,4-Diselenazolium salts (262) may be obtained by the

oxidation of the selenoamides RC(Se)NH, with iodine in n i t r ~ m e t h a n e . ~ ~ '
17 Oxathiazoles
1,2,3-Oxathiazoles.-N- Sulphonyl-a-bromo-amidines, MeCR'BrC( =NS02-
R2)NHR3, undergo intramolecular cyclization on treatment with potassium
t-butoxide to give the iminodihydro-oxathiazolines (263) in good yields; on
warming, these isomerize to the N-sulphonyl-amidines H2C=CR1C-
(=NS02R2)NHR3.291The reaction of (263; R' = R2 = Me, R3 = 4-tolyl) with
aryl or acyl isocyanates R 4 N C 0 gives a mixture of the oxazolidines (264) and
imidazolines (265), depending on R4 and on the reaction conditions.292Similar
reactions take place with electrophilic isothiocyanates and with ketones. The
reaction between ortho- amino-phenols and thionyl chloride gives the 1,2,3-
benzoxathiazole 2-oxides (238; X = O).270
1,3,2-Oxathiazoles.-Flash photolysis of the meso-ionic 4-phenyl-l,3,2-oxathi-

azolylium-5-olate gives benzonitrile sulphide, which decomposes to benzonitrile
and sulphur. The kinetics and energetics of this decomposition have been
measured in various solvents, and a mechanism for the extrusion of sulphur has
been discussed (see also Vol. 1, p. 165).293
1,3,4-Oxathiazoles.-Thermal decomposition of the oxathiazolones (266; R' =
alkyl or aryl, R2R3 = 0) gives the nitrile sulphides R'CNS, which undergo
1,3-dipolar cycloadditions with the ketones R2COR3 (R2 = CCI3, R3 = H ;
290 J. Liebscher, A. Hantschmann, and H. Hartmann, Ger. (East) P. 134 093/1979 (Chem.Abstr., 1979,
91, 39 497).
291 G. L'abbC and A. Verbruggen, Tetrahedron Lett., 1979, 49.
292 G. L'abbC, C-C. Yu, and S . Toppet, J. Org. Chem., 1979, 44, 3991.
293 A. Holm, J. J. Christiansen, and C. Lohse, J. Chem. SOC.,Perkin Trans. I , 1979, 960.
R2 = CF3, R3 = Ph) to give the 1,3,4-oxathiazolines (266; R', R2, R3 as
before).294
1,3,5-Oxathiazoles.-The reaction between aryl isocyanates R'NCO and cyano-
thioformamides NCC(S)NR2R3gives the 1,3,5-oxathiazolines (267).2'4
18 Miscellaneous Ring Systems

1,2,4-Thiatellurazoles.-The first example of this ring system (268) has been
obtained on heating the 1,3-thiazete (269) with Sb2Te3for some time.295
1,2,3,4-Thiatriazoles.-5-Arylamino- 1,2,3,4-thiatriazoIes (270; R = NHAr)
have been prepared by allowing the corresponding thiosemicarbazides
RNHC(S)NHNH2 to react with nitrous acid,296and the reaction between
PhSC(S)CI and potassium thiotosylate gives PhSC(S)S-STos, which reacts with
sodium azide to give (270; R = PhS).297
Flash photolysis of (270; R = Ar) gives the corresponding benzonitrile
sulphides ArCNS, which decompose thermally to ArCN and sulphur (cf. 1,3,4-
~ ' 1,2,3,4-oxatriazolium-5-thiolates (271; X = 0, Y = S)
o x a t h i a ~ o l e s ) . ~The
rearrange on heating with ethanolic ammonia to give the 1,2,3,4-thiatriazolium-
5-olates (271; X = S, Y = 0),and treatment of the latter with the Meerwein
reagent gives the 1,2,3,4-thiatriazoIium salts (272), which then will react with
sodium sulphide to give (271; X = Y = S).29R The reaction between (272) and
aryl-amines gives the 5-anilinothiatriazolium salts, and the latter are converted
into the 1,2,3,4-thiatriazolium-5-aminides (271; X = S, Y = NHAr) by sodium
whilst (272) and malononitrile plus triethylamine gives [271;
X = S, Y = C(CN)2].300
1,2,3,5-ThiatriazoIes.-The reaction of semicarbazide or thiosemicarbazide

derivatives with thionyl chloride gives the 1,2,3,5-thiatriazoIidin-4-one
(or the
4-thione) 1-oxides (273; R' = But or Ph, R2 = Me or Pr', X = 0 or S).3"1
294 R. M. Paton, J . F. Ross, and J. Crosby, J. Chem. Soc., Chrm. Commun., 1979, 1146.
295 K. Burger, R. Ottlinger, A. Proksch, and J. Firl, J. Chenz. SOC.,Chem. Commun., 1979, 80.
296 A. Wahab, Arzneim-Forsch., 1979, 29, 728 (Chem. Abstr., 1979, 91,74 536).
297
H. C. Hansen and A. Senning, J. Chem. SOC.,Chem. Commun., 1979, 1135.
298 R. N. Hanley, W. D. Ollis, and C. A. Ramsden, J. Chem. Soc., Perkin Trans. 1, 1979, 732.
299 R. N . Hanley, W. D. Ollis, and C. A. Ramsden, J. Chem. Soc., Perkin Trans. I, 1979, 741.
300 R. N. Hanley, W. D. Oilis, C. A. Ramsden, and I. S. Smith, J. Chem. Soc., Perkin Trans. 1, 1979,744.
301
S. D. Ziman, J. Heterocycl. Chem., 1979, 16, 895.
Five-Membered Rings: Other systems 145
1,2,3,5-Dithiadiazoles.-Trithiazyl chloride (trichlorocyclotrithiazine) will react
with nitriles RCN ( R = CC1, or Ph) to give the 1,2,3,5-dithiadiazoliumsalts (274;
R as before). The salt (274; R = Ph) may also be obtained from the benz-
amidinium salt and sulphur d i ~ h l o r i d e . ~ ' ~
X
R'N,
s-Fe
I \
,NR2
S
1,3,2,4-Dithiadiazoles.-The compound (234) has been obtained from the reac-

tion between thiazyl fluoride and hexafluorobut-2-yne (see earlier).2h5
1,3,4,2-Thiadiazaphospholes.-The reaction between methyl dithiocarbazates
RNHNHCS,Me (R = Ph or aryl) and phosphorus trichloride gives compound
(275), whilst with PSCI, the product is (276; R = Ph).244The 1,3,4,2-thiadi-
azaphospholidin-5-one 2-sulphide (277) is obtained as a mixture of isomers on
treatment of 1,2-di-t-butyldiaziridinonewith the reagent (278).303
R R
(277) (278)
PART 111: Other Five-Membered Ring Systems by G. V. Boyd
1 Introduction
This Bart deals with the remaining heterocyclic compounds that contain five-
membered rings. Monocyclic systems, their benzo-analogues, other annelated
heterocycles, and compounds containing two or more linked five-membered rings
are reviewed first. There follows a survey of those bi- and poly-cyclic systems in
which a five-membered ring of the previous type is fused to a heterocycle
containing five, six, seven, or eight atoms. A n exception has been made in the
case of tetrathiafulvalenes, which follow the dithioles, because of their close
relationship to these compounds. The order in each section is generally that of
increasing saturation, so that the fully conjugated 'aromatic' compounds are
302 G. G. Alange, A. J. Banister, B. Bell, and P. W. Millen, J. Chem. SOC.,Perkin Trans. I, 1979, 1192.
303
G. L'abbe, J. Flemal, J. P. Declercq, G . Gerrnain, and M. Van Meerssche, Bull. SOC. Chirn. Belg.,
1979, 88, 737.
146 H e teroc y c 1ic Che m is try
mentioned first and completely hydrogenated compounds are discussed last. For
some ring systems, e.g. furans, pyrroles, and indoles, it was found convenient to
survey methods of synthesis and reactions in separate sub-sections.
As in the previous year, the Reporter had to be severely selective: only about
half of the thousand relevant articles are mentioned briefly. The reader is referred
to the original sources for further information and much fine chemistry.
2 Reviews
Six articles cover general aspects of heterocyclic chemistry: 1,3-dipolar cyclo-
reversions,' syntheses with arylnitrenes2*3and a -metallated i~ocyanides,~ and
photo-oxygenation of nitrogen heterocycles,"' while others deal with more
specialized subjects, i.e. preparation and use of halogeno-lac tone^,^ aspects of
the chemistry of furan,* 1-hydroxy-indoles,' ring-opening of azoles by the action
of amines,'" the use of 2-chlorobenzoxazolium ( I ) and other heterocyclic onium
salts for dehydration and condensation reactions," the synthesis of monosub-
stituted tetrathiafulvalenes (2),12 cycloadditions of azoles containing three
h e t e r o a t o m ~sydnone
,~~ imines (3),14 the conversion of acyl-benzofuroxans into
nitro-indazoles (cf. p. 199)," and advances in the chemistry of pyrrolizidine"
and ind01izine.l~
3 Systems with One Heteroatom, and their Renzo-analogues

Furans.-Formation. Irradiation of a mixture of benzoylacetylene and an
alcohol, RCH20H,yields the furan (4;R = H, Me, Et, or Bu').I8 The heteroaryl-
1
G Bianchi, C. De Micheli, and R. Gandolfi. Angew. Chern., Znt. Ed. Engl., 1979, 18, 721.
2
B. Iddon, 0. Meth-Cohn, E. F. V. Scriven, H. Suschitzky, and P. T. Gallagher, Angew. Chem., Znt.
Ed. Engl., 1979,18,900.
?
V. P. Semenov, A. N. Studenikov, and A. A. Potekhin, Khirn. Geterotsikl. Soedin., 1979, 579.
4
U. Schollkopf, Pure Appl. Chem., 1979, 51, 1347.
5
H. H. Wasserman and B. H. Lipshutz, Org. Chrm. ( N .Y.1, 1979,40 (Singlet Oxygen), p. 429 (Chem.
Abstr., 1980, 92, 22 405).
6
M. V. George and V. Bhat, Chem. Rev., 1979,79,447.
7
M. D. Dowle and D. I. Davies, Chem. SOC.Rev., 1979,8, 171.
8
'Collection of Lectures of the 3rd International Symposium of Furan Chemistry', ed. J. Kovac,
Slovak Technical University, Faculty of Chemical Technology, Bratislava, Czechoslovakia, 1979
(Chem. Abstr., 1980,92, 180 974).
9
R. M. Acheson, Stud. Org. Chrm. (Amsterdam), 1979, 3 (New Trends Heterocycl. Chem.), p. 1
(Chem. Abstr., 1980, 92,41 651).
10
A. Antonova and D. Simov, Khim. Geterotsikl. Suedin., 1979, 1587.
11
T. Mukaiyama, Angew. Chem., Int. Ed. Engl., 1979, 18,707; Pure Appl. Chem., 1979, 51, 1337.
12
D. C. Green, Ann. N . Y. Acad. Sci., 1978, 313, 361.
13
R. B. Mitra, G . H. Kulkarni, G. S. Shirwaiker, and R. S. Jagtap, Stud. Org Chem. (Amsterdam),
1979, 3 (New Trends Heterocycl. Chem.), p. 309 (Chem. Abstr., 1980,92, 58 630).
l4 V. G. Yashunskii and L. E. Kholodov, Usp. Khitn., 1980, 49, 54.
A . J. Boulton and A. R. Katritzky, Adv. Pestic. Sci.,Plenary Lect. Symp. Pap. Int. Congr. Pestic.
Chem., 4th, 1978,2, 58 (Chem. Abstr., 1979,91, 74493).
l6 D . J. Robins, Adv. Heterocycl. Chem., 1979, 24, 247.
F. J. Swinbourne, J. H. Hunt, and G . Klinkert, Adu. Heterocycl. Chem., 1978, 23, 103.
T. Nishio and Y. Omote, J. Chem. SOC.,Perkin Trans. I , 1979, 1703.
Five-Membered Rings: Othsr systems 147
furans ( 5 ; R = 2-furyl, 2-thienyl, or 2-selenophenyl) have been obtainecj by the
action of dimethyl acetylenedicarboxylate on the sulphuranes Me2S-CH-
COR.19 A general furan synthesis is exemplified by the conversion of the
sulphide (6) into compound (7) by the action of titacium tetrachloride.20 The
dioxolan (8) serves as the starting material for the preparation of mono- and
di-substituted furans; its reaction with butyl-lithium, followed by an aldehyde
R'CHO, gives an alcohol, which cyclizes to (9; R2 = H) in the presence of
toluene-p-sulphonic acid, while successive treatment of (8) with butyl-lithium,
an alkyl halide R2X, butyl-lithium, and an aldehyde R'CHO leads to a product
with substituents in positions 2 and 3, e.g. (9; R' = n-CsHI7, R2 = Me).21 A
procedure for the preparation of 3-alkyl-furans employs the di-lithio-derivative
(8) (9) (10)

(10), obtained from but-2-yne- 1,4-diol, dihydropyran, and butyl-lithium. Alkyl-
ation, followed by treatment with mineral acid, affords the product (9; R' = H,
R2 = alky1).22Sulphuric acid converts diethyl aa'-diacetylsuccinate into the ester
(1l),contrary to a previous Base-catalysed cyclization of the acetylenic
ester (12; R = Bu') yields the cyclobutafuran (13); in contrast, dipropargyl ether
(12; R = H) itself forms the dimer (14).24
Et0,C
M e 0
o M e
C0,Et
0
/
\
CH,C=CR
CH,C-CR
ozBuI
Bu'
I --.
(11) (12) (13) (14)
+
An intramolecular Wittig reaction of the phosphonium salt Ph3P-CH2-
CH2CH20COPh Br- yields the dihydrofuran (15).25 Compound (16) is
formed from styrene and acetone in the presence of lead dioxide by a free-radical
mechanism.26 The A3-dihydrofuran (17) is produced by the action of silver
fluoroborate on the allenic alcohol HOCH,CH=C=CM~BU';~' another com-
pound of this type, namely (18), is the product of the reaction of the sulphurane
H2C=SMe2 with salicylideneacetone.28
l9 N. N. Magdesieva, N. Le Nguyen, and N. M. Koloskova, Zh. Org. Khim., 1979,15,609.
20
S. Kano, Y. Tanaka, S. Hibino, and S. Shibuya, J. Chem. Soc., Chem. Commun., 1979, 238.
21 H. Kotake, K. Inomata, H. Kinoshita, S. Aoyama, and Y. Sakarnoto, Heterocycles, 1978, 10, 105;
K. Inomata, Y. Nakayama, M. Tsutsumi, and H. Kotake, ibid., 1979, 12, 1467.
22 M. Staehle and M. Schlosser, Angew. Chem., Znt. Ed. Engl., 1979, 18, 875.
23 H. M. Fales and R. J. Highet, J. Org. Chem., 1980, 45, 1699.
24 P. J. Garratt and S. B. Neoh, J. Org. Chem., 1979,44, 2667.
2 5 A. Hercouet and M. Le Corre, Tetrahedron Lett., 1979, 5.
26 M. Hajek, P. Silhavy, and J. Malek, Collect. Czech. Chem. Commun., 1979, 44, 2393.
" L. I. Olsson and A. Claesson, Synthesis, 1979, 743.
28 P. Bravo and C. Ticozzi, J. Chem. SOC.,Chem. Commun., 1979,438.
148 Heteroc y c 1ic Chemistry
Me R2 R3
Bu' r-=
R 1n 0R 2 .
(15) R' = H, R2 = Ph (17) (19) R2 = SPh,R3 = Me
(16) R' = Ph, R2 = Me (20) R' = Ph
(21) R' = R2 = H, R3 = Me
Notable new general syntheses of butenolides include the addition of the

three-carbon synthon Li(PhS)C=CMeC02Me :o aldehydes R'CHO (R' = alkyl
or aryl) to yield the thioethers (19),29the related reaction of lithio-p-lithio-
acrylates R2CLi=CR3C02Li with benzaldehyde to give compounds (20;
R2 = H or Me),30 and the formation of (21) from the iodinated ally1 alcohol
ICMe=CHCH20H and carbon monoxide in the presence of bis(tripheny1phos-
p hine)palladium (11) chloride .3 1 Chloral reacts with dimethy1 (benzylamino)f u -
marate to yield the butenolide (22), whereas aromatic aldehydes give hydroxy-
pyrrolinones (23).32The total synthesis of piperolide (24) has been reported.33
Me02C OH
Me0,C NHCH,Ph
Ar
C13C CH,Ph OMe
Treatment of the 1,5-diene (2,Z)-CHD=CHCH2CH2CH=CHD with

potassium permanganate results in stereospecific oxidative cycloaddition to give
40% of the tetrahydrofuran ( 2 5 ) , which possesses four chiral centres; the
(E,E)-isomer behaves in an analogous 2,2-Dialkoxytetrahydrofurans
are formed from epoxides and keten acetals; thus epichlorhydrin reacts with
MeCH=C(OMe), in the presence of zinc chloride to afford compound (26).3'
The chloro-furanone (27) is obtained as a mixture of cis- and trans-isomers from
styrene and trimethylsilyl dichloroacetate in the presence of bis(tripheny1phos-
phine)ruthenium(II) chloride.36 Total syntheses of both enantiomers of the
pheromone (28) of the Japanese beetle (Popillia j a p o n i ~ a ) ~and
' of chalcogran
(29),38the principal pheromone of Pityogenes chalcographus (L.), have been
described.
Reactions of Furans. Furan is alkylated at position 2 on treatment with olefins
in the presence of palladium(r1) acetate and copper(I1) a ~ e t a t e . ~
2-Lithiofuran,
'
formed by lithiation of furan, yields the 'ate complexes' (30) on treatment with
2y K. Isobe, M. Fuse, H. Kosugi, and H. Hagiwara, Chem. Lett., 1979, 785.
30 D. Caine and A. S . Frobese, Tetrahedron Lett., 1978, 5167.
31 A. Cowell and J. K . Stille, Tetrahedron Lett., 1979, 133.
32 G. Dornschke, 2. Chem., 1980, 20, 16.
33 H. Achenbach and J. Witzke, Tetrahedron Lett., 1979, 1579.
34 J. E. Baldwin, M. J. Crossley, and E. M. M. Lehtonen, J. Chem. SOC.,Chem. Commun., 1979,913.
3s J . W. Scheeren, F. J. M. Dahrnen, and C. G. Bakker, Tetrahedron Lett., 1979, 2925.
36 H. Matsurnoto, K. Ohkawa, S . Ikernori, T. Nakano, and Y. Nagai, Chem. Lett., 1979, 1011.
37 K. Sato, T. Nakayarna, and K . Mori, Agric. Biol. Chem., 1979, 43, 1571 (Chern.Abstr., 1980, 92,
6327).
38 K. Mori, M. Sasaki, S . Tornada, T. Suguro, and S . Masuda, Tetrahedron, 1979,35, 1601.
39 0. Maruyarna, M. Yoshidorni, Y. Fujiwara, and H. Taniguchi, Chem. Lett., 1979, 1229.
trialkylboranes; subsequent oxidation with iodine affords 2-alkyl-f~rans.~’N-

Methylpyrrole behaves similarly.41Treatment of 2- and 3-furoic acid with lithium
di-isopropylamide produces the dilithio-compounds (31) and (32), respectively;
these react normally with methyl iodide or with carbonyl Meerwein
arylation of furfural with arenediazonium salts in the presence of copper(I1)
chloride takes place at C-5 to afford [33; Ar=p-N02C6H4or 2,4-(N02)2C6H,].43
5-Nitrofuran-2-aldehyde is attacked by 1-adamantyl radicals to give the ‘ipso’-
intermediates (34) and (35); only the latter yields an ‘@so’-substitutionproduct,
i.e. 5-(l-adamantyl)f~ran-2-aldehyde.~~ The reaction of furan with N-bromo-
succinimide and mercury( 11) chloride furnishes the bifuryl ( 36).4s
Ad = 1-adamantyl
The Diels-Alder reaction of maleic anhydride with 3,4-dimethoxyfuran

affords endo- and exo-adducts at about the same rate, in contrast to furan, where
the endo-isomer is the product of kinetic control. In both cases the exo-adduct is
thermodynamically more stable.? 3,4-Dimethoxyfuran and p-benzoquinone
give the endo-compound (37)’ whereas in the reaction with 2,3-dimethyl- 1,4-
benzoquinone only the exo-adduct (38) was detected.47The Diels-Alder adduct
(40) of methyl acrylate to 2-amino-3-cyano-4,5-dimethylfuran (39) is readily
40 I. Akimoto and A. Suzuki, Synthesis, 1979, 146.
41 T. Sotoyama, S. Hara, and A . Suzuki, Bull. Chem. SOC.Jpn., 1979, 52, 1865; E. R. Marinelli and
A. B. Levy, Tetrahedron Lett., 1979, 2313.
42 D. W. Knight, Tetrahedron Lett., 1979, 469.
43 S. Farinas, C. R. Rodriguez Palacio, and I. Ramos Raimundo, CENTRO, Ser.: Quim. Technol.
Quim., 1977, 5, 75 (Chem. Abstr., 1979, 91, 175 100).
44
P. Cogolli, L. Testaferri, M. Tiecco, and M. Tingoli, J. Chem. SOC., Chem. Commun., 1979, 800.
45 J . Reisch and I. Mester, Chem. Ber., 1979, 112,1493.
46 P. X. Iten, A. A. Hofmann, and C. H. Eugster, Helu. Chim. Acta, 1979, 62, 2202.
47 A. A. Hofmann, I . Wyrsch-Walraf, P. X. Iten, and C. H. Eugster, Helu. Chim. Acta, 1979,62,2211.
(37) R' = H, R ~ - R =~ COCH=CHCO

(38) R'-R' = COCMe=CMeCO, R2 = H
(39) (40) (41)

converted into the anthranilic acid derivative (41).48The ready formation of the
intramolecular Diels-Alder adduct (43) from the magnesium salt of N-furfuryl-
N-(2-hydroxyphenyl)acrylamide (42) has been attributed to internal co-ordina-
tion of the Sensitized photo-oxygenation of furans yields trioxa-
bicyclo[2.2.l]heptenes (44; R', R' = H, alkyl, or Ph) as primary
Fi + @ 8; 0
R'
N
I
C,H,OH
O
-0
TC,H,OH
o -0
(44)
(42) (43)
The (chloromethy1)furan (45) gives mainly the butenolide (46) on treatment
with aqueous potassium cyanide.5' A detailed study of the reaction of furfural
with primary aromatic amines has shown that 2,4-di(arylamino)cyclopent-2-
enones (47) are usually formed; intermediate 4,5-di(arylamino)cyclopent-2-en-
ones (48) are occasionally isolated.'* The zinc-chloride-induced rearrange-
ment of the 2-fury1 alcohols (49; R = Bu, allyl, or Ph) to the cyclopentenolones
(51) is thought to involve the cations (50) as key intermediate^.'^ The enolate
that is formed by the action of butyl-lithium on 2-benzylfuran has been isolated
Ph Ph Ph Ph
O0C H , C I --+ 0f l 0
M e 0QNI-IAr
(45) (46) R'
(47) R' = H, R2 = ArNH
(48)R' = ArNH, R2 = H
48 W. J . Nixon, Jr., J. T. Garland, and C. D . Blanton, Jr., Synthesis, 1980, 56.
49 T. Mukaiyama, T. Tsuji, and N. Iwasawa, Chem. Lett., 1979, 697.
W. Adam, H. J. Eggelte, and A . Rodriguez, Synthesis, 1979, 383.
51 K. Yamamoto and A. Tanaka, J. Heterocycl. Chem., 1979, 16, 1293.
'* K. G . Lewis and C. E . Mulquiney, Aust. J. Chem., 1979, 32, 1079.
53 G . Piancatelli, A. Scettri, G. David, and M. D'Auria, Terrahedron, 1978, 34, 2775.
as the trimethylsilyl compound (52); similarly, successive treatment of the
(phenylally1)furan (53) with butyl-lithium and trimethylsilyl chloride affords the
allene (54).54Flash vacuum pyrolysis of the tetrahydrobenzofuran ( 5 5 )results in
a retro-Diels-Alder reaction to give ethylene and 2,3-dimethylenedihydrofuran
(56).55
SiMe,
Proton n.m.r. spectroscopy of the annulenes (57) and (58) indicates that the
former is rigid and paratropic (sixteen r-electrons in the periphery), whereas the
latter is conformationally mobile and sustains a diamagnetic ring-current, owing
. ~ ~ [ 2 r + 1 4 ~ 1cyclo-adduct of
to the presence of eighteen r - e l e c t r o n ~ The
dimethyl acetylenedicarboxylate to the oxofuranophane (59) has been dehy-
drogenated to the [5]annuleno[ 1 Slannulenone (60),which is paratr~pic.~’
(57)
(59)
54 K . Atsumi and I. Kuwajima, J. A m . Chem. SOC., 1979,101,2208.

” J. Jullien, J. M. Pechine, F. Perez, and J. J. Piade, Tetrahedron Lett., 1979, 3079.
56 H. Ogawa, J. Mukae, Y. Taniguchi, and H. Kato, Tetrahedron Lett., 1978, 4929.
” H. Ogawa and A. Chisaka, Tetrahedron Lett., 1978,4811.
The spiro-dihydrofuran (6 1) is converted into the cyclobutane derivative (62)
under the influence of trifluoroacetic The lithium dienolate (64), derived
from the furanone (63),yields solely y-alkylated products on treatment with alkyl
halides.59Thermolysis of the t-butylperoxybutenolide (65) produces about equal
amounts of the hydroxy-furanone (67) and the indenone (68), presumably uia
the oxide radical (66).60Attack of iodide ion on the salt (69) results in the
formation of methyl iodide, butanolide, and (surprisingly) methyl 4-
iodobutanoate.61 A description of a study of the photochemical rearrangement
of the tetrahydrofurans (70) to the bicyclic oxetans (71) has been presented.62
Ph Ph 0,CPh
Ph
(65) R = But02
a p
0
h n o,*Y'OMe
(66) R = 0. (68) (69) BF4-
(67) R = OH
Benzofurans and Other Annelated Furans.-A new synthesis of benzofurans (73)

is by the reaction of the phosphonium salt (72) with acid chlorides RCOCl in the
. ~ ~ benzofuran (74) results from the condensation
presence of t r i e t h ~ l a m i n e The
. ~ ~ instances of the formation of
of hexafluorobenzene with a ~ e t y l a c e t o n eThree
benzofurans from 0-aryl-hydroxylamines, i.e. the oxygen analogue of the Fischer
indole synthesis, have been reported: 0-phenylhydroxylamine hydrochloride
and benzenesulphonylacetone give a 2 : 1 mixture of compounds (73; R' =
CH2S02Ph)and (75),65the oxime ether (76) is converted into the aldehyde (77;
@R1 F
Fm
\ 0 Me
(73) R2 = H
(72) (75) R' = Me, R2 = S 0 2 P h (74)
E. B. Frolov, S. N. Anfilogova, and E. S. Balenkova, Zh. Org. Khim., 1979,15, 1780.
59 A. B. Smith, 111, and R. M. Scarborough, Jr., Tetrahedron Lett., 1978, 4193.
6o J. S. Weinberg and A. Miller, J. Org. Chem., 1979, 44, 4722.
'' N. Beaulieu and P. Deslongchamps, Can. J. Chem., 1980, 58, 164.
62 A. Padwa and T. Brookhart, J. Org. Chem., 1979, 44,4021.
63 A. Hercouet and M. Le CarrC, Tetrahedron Lett., 1979, 2145.
64 Y. Inukai, T. Sonoda, and H. Kobayashi, Bull. Chem. SOC. Jpn., 1979,52,2657.
65 L. A . Samarina, L. M. Shakova, and V. A. Zagorevskii, Khim. Geterotsikl. Soedin., 1979, 1176.
R = CHO) by the action of the dimethylformamide-phosphorus oxychloride
complex,66and 0-(p-nitropheny1)hydroxylamineand ethyl benzoylacetate yield,
inter aliu, the benzofuran (77; R = COzEt).67Sodium salts of 2-hydroxyben-
zofuran-esters, e.g. (78), are produced by the action of dimethyl chloromalonate
on hydroquinones.68
02N 0;J Ph
O2N@,,,
' 0
H O
\
Me
D CO
A Me
o
H
(76) (77) (78)
Pyrolysis of tri-, tetra-, and penta-chlorobenzenes affords mixtures of chlor-

inated dibenzofurans and dibenzo-p-dioxins," and chlorinated diphenyl ethers
cyclize in the presence of palladium acetate to polychloro-dibenzofurans.70The
action of malononitrile on tetrahydroxy-p-benzoquinoneleads to the benzo-
difuran (79), contrary to a previous report.71 The acid-catalysed condensation
of quinones with phenols has been studied; p-benzoquinone and resorcinol, for
example, afford compound (80).72 Naphtho[2,3-b]furan-4,9-diones(81; R' =
Me or Ph; R2 = Ac, Bz, C 0 2 E t ,or CN) are obtained from 2,3-dichloronaphtho-
1,4-quinone and compounds R'COCH2R2 in DMF that contains potassium
The action of mineral acids on p-benzoquinone produces a mixture of
complex benzofurans, which includes (82) and (83).74Bases convert the ben-
zofuranone (84) into the tetrameric compound (85), contrary to an earlier
H2N (yJ-jNH2
1R@ " O W O H 0
CN 0
0
0 0
(80) (81)
(79)
" O O H
(82)
(83)
66 M. A . Kira, M. 0. A . Rahman, and Z . M. Nofal, Egypt. J. Chem., 1976, 19, 109.
67 V. A . Zagorevskii, L. A . Samarina, L. M. Sharkova, and L. A . Aksanova, Khim. Geterotsikl. Soedin.,
1979,1031.
A . H. Renfrew, S. B . Bostock, and C. M. Ecob, J. Chem. SOC., Perkin Trans. 1, 1979, 2382.
69 H. R. Buser, Chemosphere, 1979,8, 415.
70 A . Norstroem, S. K. Chaudhary, P. W. Albro, and J. D. McKinney, Chemosphere, 1979, 8, 331.
71 R. Peltzmann, B. Unterweger, and H. Junek, Monarsh. Chem., 1979,110, 739.
72 H. E. Hoegberg and P. Komlos, Acta Chem. Scand., Ser. B, 1979, 33, 271; H. E. Hoegberg, J.
Chem. Soc., Perkin Trans. 1, 1979,2517.
73 H.-S. Kuo, K. Hotta, M. Yogo, and S. Yoshina, Synthesis, 1979, 188.
74 H. Erdtman and H. E. Hoegberg, Tetrahedron, 1979,35, 535.
a s ~ i g n m e n t .The
~ ~ blue-black compound ‘Blue 342’, formed from dihydro-
phenalen-2-one (86) and bromine, has structure (87).76
The tosylhydrazone (88; X = 0)decomposes in the gas phase to the carbene
(89), which cyclizes to a mixture that contains mainly the dihydrobenzofuran (90)
and dihydrobenzopyran (91) and in which the former predominates; in the case
of the sulphur analogue (88; X = S) the ratio of the two types of product is
~ lithium salt (92) of the 2-methyleneallyi dianion reacts with
r e v e r ~ e d . ’The
o-phthalaldehyde to yield the dihydroisobenzofuran (93), together with the
methylenebenzocycloheptanediol(94).78A mixture of the positional isomers (96;
CH,CMe=CH,
CH2
2~i+
(93) OH
(92)
M e d ‘C0,H
M e
CO,H
- ~
R’ \
2 & r ~
” J. Bergman, B. Egestad, and D. Rajapaksa, Acta Chem. Scand., Ser. B, 1979, 33,405.
76 A. S. Kende, R. Greenhouse, and J. A. Hill, Tetrahedron Lett., 1979, 2867.
77 W. D. Crow and H. McNab, Aust. J. Chem., 1979, 32,99.
78 R. B. Bates, W. A. Beavers, B. Gordon, 111, and N. S . Mills, J. Org. Chem., 1979, 44, 3800.
THC02But
-
E‘”.” (97)
@
\ ’ 0 CH,Br
\
CH, Br
(99) (100)
R’ = H, R2 = Me) and (96; R’ Me, R2 = H) is obtained by oxidative decar-
=
boxylation of the bicyclo[4.1 .O]hept-3-ene- 1,6-dicarboxylic acid (95) with lead
tetra-a~etate.’~The amino-acid (97), prepared from C- (o-hydroxypheny1)glycine
and t-butyl azidoformate, cyclizes to the aminobenzofuranone (98); this type of
product exhibits chemiluminescence when exposed to oxygen in the presence
of a base.80 Treatment of 2,2’-di(bromomethy1)benzil (99) with potassium t-
butoxide results in an unusual intramolecular nucleophilic substitution to give
the spiro-compound
The hydroxynaphthyl ketones (101; R = Me or Ph) are cyclized to the
naphthofurylium salts (102) by perchloric acid.82 2-Phenyl-SH-naphtho[ 1,8-
bclfuran-2-one (103) undergoes fission to the ketone (101; R = Ph) in
methanol-perchloric acid; condensation with diphenylketen yields compound
(104), with elimination of carbon dioxide.83
+
R
(102) c104- (103) R = 0
(104) R = CPh2
Treatment of the furotropone (105) with the keten (106) leads to the furo-
heptafulvalene ( 107).84 2H-Cyclohepta[b]furan-2-one (108) undergoes two-
fold [ST + 2 ~ cycloaddition
1 to 6,6-dimethylfulvene to yield, after loss of
carbon dioxide, the diazulenofulvene (109), accompanied by the rearranged
azulenonaphthofulvene (1
’’ N. Galloway and B. Halton, Aust. J. Chem., 1979, 32, 1743.
G. J. Lofthouse, H. Suschitzky, B. J. Wakefield, R. A. Whittaker, and B. Tuck, J. Chem. Soc., Perkin
Trans. I, 1979, 1634.
81 M. Verhage, D. A . Hoogwater, J. Reedijk, and H. Van Bekkum, Tetrahedron Lett., 1979, 1267.
V. V. Mezheritskii, V. V. Tkachenko, 0. N. Zhukovskaya, and G. N. Dorofeenko, Z.h. Org. Khim.,
1979,15,881; V. V. Mezheritskii, 0. N. Zhukovskaya, and V . V . Tkachenko, Vses. hhuchn. Konf.
Khim. Tekhnol. Furanovykh Soedin., [Tezisy Dokl.], 3rd, 1978, 150 (Chem. Abstr., 1980, 92,
180 911).
83 R. Neidlein and E. Bernhard, Liebigs Ann. Chem., 1979, 959.
84 T. Asao, N. Morita, and K. Kato, Heterocycles, 1978, 11, 287.
I. Kikuchi, H. Ohmi, M. Yasunami, and K. Takase, Koen Yoshishu-Hibenzenkei Hokozoku Kagaku
Toronkai [oyobi] Kozo Yuki Kagaku Toronkai, 12th, 1979,65 (Chem. Abstr., 1980,92, 198 1 5 5 ) .
Pyrroles.-Formation. A general synthesis of 2-aryl-pyrroles (112) is by cycliz-

ation of the esters (11 l ) , which are obtained from unsaturated aldehydes and
methyl azidoacetate.8h Tliermolysis of the acetylene (113; Ar = p-MeC6H,)
gives N-(p-toly1)pyrrole with the elimination of p - t h i o ~ r e s o l .The
~ ~ pyrrole
derivative (115) is the product of the action of benzylamine on tri-(t-
buty1thio)cyclopropenylium perchlorate (114).88Azoalkenes combine with p-
dicarbonyl compounds or with enamines to yield derivatives of N-aminopyrrole:
thus the ester (116) and ethyl acetoacetate form (117).89The base-catalysed
addition of methyl propiolate to toluene-p-sulphonylmethyl isocyanide,
TosCH,NC, gives the ester (118).90 The dipolar cyclo-adduct (120) of
piperidinocyclopentene to the azo-compound (119) forms the N-(tosyl-
amino)pyrrole derivative ( I 2 1) and piperidine on heating."
CH,C'ECCH,
Ar + Ar I ( C
NO , M e / \
H ArS NHAr
H~co2Et EtO,C C0,Et

Bu'S
SBu'
c10;
--+ Ph O;;ll
N
H
Me N
II
N
M e 0 NM e s
I
NHC0,Me
0s N 10s
(119) (120) (121)
86 J . P. Boukou-Poba, M. Farnier, and R. Guilard, Tetrahedron Lett., 1979, 1717.
0. S. Thyagarajan and P. E. Glaspy, J. Chem. Suc., Chem. Cummun., 1979, 51 5.
88 Z. Yoshida, Japan. P. 79 44 669 (Chem. Abstr., 1980,92, 6404).
A. G . Schultz, W. K. Hagmann, and M. Shen, Tetrahedron Lett., 1979, 2965.
90 H. Saikachi, T. Kitagawa, and H. Sasaki, Chem. Pharm. Bull., 1979, 27, 2857.
91 S. Sommer, A n g u w . Chum., I n t . Ed. Engl., 1979. 18, 695.
The allene PrCH=C=CHCH2NH2 isomerizes to the 3-pyrroline (122) under
the influence of silver t e t r a f l u ~ r o b o r a t e .Photolysis
~~ of aroyl azides in the
presence of diketen (123) yields the hydroxy-pyrrolinones ( 124).93X-Ray analy-
sis has shown that the adduct of the imine Pr"CH=NPr' to N-phenylmaleimide
has structure ( 125).94Treatment of dichloromaleimide with ethoxycarbonyl-
methylenetriphenylphosphorane affords the Wittig product (126).95The forma-
tion of the pyrrolidinone (128) in the thermolysis of the N-cyclohexenylacryl-
amide (127) represents an intramolecular ene-reaction (see arrows).y6 The
perfluoropyrrolidinone (130) results from the reaction of the cyclobutane (129)
with potassium Pyrrolidinols (131) are obtained in moderate yields by
photochemical cyclization of the amides ArCOCH2CH2NBzCH2Ph.98
HO Et CH,CONHPh
I Pr
Et0,CHC a
Reactions of Pyrroles. Pyrroles are efficiently alkylated at the nitrogen atom by
alkyl halides in the presence of potassium hydroxide and 18-cr0wn-6.~~ In a study
of the metallation of a series of N-alkyl-pyrroles by butyl-lithium it was found
that the ratio of 2,4- to 2,5-dilithio-compounds increases with increasing bulk of
the alkyl group.'oo Nitration of 1-methylpyrrole yields a mixture of 2,3-, 2,4-,
2,5-, and 3,4-dinitro-compounds, while 1,2-dimethylpyrrole gives the three
possible mononitro- as well as 3,4-, 3 3 - , and 4,5-dinitro-derivatives."
92 A. Claesson, C. Sahlberg, and K. Luthman, Acta Chem. Scand., Ser. B,1979, 33, 309.
93 T. Kato, Y. Suzuki, and M. Sato, Chem. Pharm. Bull., 1979, 27, 1181.
94 G. Audisio, W. Porzio, L. Zetta, and P. Ferruti, J. Chem. SOC.,Perkin Trans. 2, 1979, 1391.
95 M. Augustin, B. Schneider, and M. Kohler, J. Prakt. Chem., 1979,321, 797.
96 E. Schmitz, U. Heuck, and H. Preuschhof, J. Prakt. Chem., 1979, 321, 387.
97 M. Takashima and J. M. Shreeve, Inorg. Chem., 1979, 18,3281.
98 H. G. Henning, T. Dietzsch, R. Groh, and T. Szabo, Z. Chem., 1979,19,218.
99 E. Santaniello, C. Farachi, and F. Ponti, Synthesis, 1979,617.
loo D. J. Chadwick and I. A. Cliffe, J. Chem. SOC.,Perkin Trans. 1, 1979, 2845.
lo' L. Grehn, Chem. Scr., 1979,13, 67.
1-Methyl-3-nitropyrrole undergoes di-nitration mainly at C-2 and C-4, and at

C-3 and C-4.'02 Electrophilic substitution (nitration, halogenation, and acetyl-
ation) of 2-(trichloroacetyl)pyrrole occurs almost entirely at position 4, and thus
provides a method for the preparation of 4-substituted pyrrole-2-carboxylic
acids.'03 There is evidence that the bromination of the ester (132) to yield the
bromomethyl-compound (133) proceeds by way of a mixture of o-intermediates,
in which bromine is attached to each carbon atom of the ring.lo4N-Alkyl-pyrroles
react with ethyl diazoacetate under copper catalysis to give both 2- and 3-
pyrrylacetic esters (134), the proportion depending on the nature of the copper
compound and o n the bulk of the alkyl group.'os Diethyl azodicarboxylate forms
the di-adducts (135) with N-alkyl- or N-aryl-pyrroles.Io6 Photoaddition of
aliphatic aldehydes or ketones to pyrrole affords the alcohols (136; R', R2 = H or
alkyl).'" Attention is drawn to the preparation of 2-alkyl-N-methyl-pyrroles via
'ate'-complexes, mentioned on p. 149.
(133) R = CH2Br (134) (135) E = COZEt (136)

N-Amino-pyrroles undergo Diels-Alder reactions with dimethyl acetylene-
dicarboxylate; thus l-amino-2,3,4,5-tetramethypyrroleforms the phthalic
ester (138) by extrusion of H2N-N: from the intermediate adduct (137).lo8
Treatment of l-methoxycarbonyl-2,5-dimethylpyrrolewith the acetylenic ester
results in the 2H-pyrrole (139) by an unusual migration of the ester group.1o9
The singlet carbene (14 l ) , generated by irradiation of 3-diazo-2,5-diphenylpyr-
role (140), reacts differently with benzene derivatives, depending on the presence
of electron-withdrawing or -releasing groups. The former yield all possible
isomers of substituted cyclo-octatetraenopyrroles (143; R = CN or NO,), while
the latter, e.g. toluene, afford products (144; R = 0- or p-Me) of electrophilic
substitution. The suggested mechanism shown in Scheme 1 involves the spiro-
norcaradiene (142) as the key intermediate for both types of product.110
(137) (138)
E = C02Me
'02 G. Doddi, P. Mencarelli, A. Razzini, and F. Stegel, J. Org. Chem., 1979, 44, 2321.
P. Belanger, Tetrahedron Lett., 1979, 2503.
G. Angelini, C. Giancaspro, G . Illuminati, and G . Sleiter, J. Org. Chem., 1980, 45, 1786.
Io5 B. E. Maryanoff, J. Org. Chem., 1979, 44,4410.
Io6 C. K. Lee, S. J. Kim, and C. S. Hahn, J. Org. Chem., 1980, 45, 1692.
'"' G. Jones, 11, H. M. Gilow, and J. Low, J. Org. Chem., 1979, 44, 2949.
A . G. Schultz and M. Shen, Tetrahedron Lett., 1979, 2969.
lo9 R. A . F. Matheson, A. W. McCulloch, A . G. McInnes, and D. G . Smith, Can. J. Chem., 1979, 57,
2743.
M. Nagarajan and H. Shechter, J. A m . Chem. Soc., 1979,101,2198.
P h N
o Pk 2h ----* P h N
a P h PhR Ph
-+ pR+N Ph p Nh p R
I
- g: R
[IS]shifts
Ph H
N
Scheme 1 (143)
The [2.2](2,5)pyrrolophane (145; Ar = p-BrC6H,) undergoes loss of one of

the aryl groups and a complex rearrangement to the tetracyclic compound (146)
under the influence of acids.'" The 2H-pyrroles (147) and (148) both rearrange
at 270 "C to give the same product, i.e. the pyrrole (149); the process involves
two successive [1,5]-shifts - of a phenyl and then a methyl group in the first case,
and of a phenyl group in the second."2 The action of N-bromosuccinimide on
2-cyano-1-pyrroline 1-oxide (150; R' = CN) produces the bromo-derivative
(151), which can be converted into the corresponding nitro- and hydroxy-
compounds; triethylamine yields the elimination product ( 152).l13The 2-phenyl-
and 2-t-butyl-analogues (150; R' = Ph or But) do not give stable 3-bromo-
0-Q
derivative^."^
-
\ P h G RMe2
\ I (147)R' = Ph, R2 = Me
(146)
(145) (148)R 1 = Me,R2 = Ph
Ph Me
P h N
n M e
N
0 N
CN
H I I
(149) 0- 0-
(150)R2 = H (152)
(151)R' = CN, R2 = B r
W. W. Paudler, R. L. Mahaffey, and J. L. Atwood, J. Org. Chem., 1979, 44, 2498.
11* A. Laurent, P. Mison, A. Nafti, and N. Pellissier, Tetrahedron Lett., 1979, 1587.
D. St. C . Black, N. A. Blackman, and R. F. C . Brown, Aust. J. Chem., 1979, 32, 1785.
*14 D. St. C. Black and N. A. Blackman, Aust. J. Chem., 1979,32,1795.
160 Heteroc yclic Chemistry
Hydrolysis of the trifluoroacetyl-derivative (153) produces a mixture of the
pyrrolin-2-ones (154) and (155); the latter is unstable, and gradually isomerizes
to the former."' Whereas the N-benzyl- and N-phenyl-pyrrolin-3-ones (156;
R = CH2Ph or Ph) exist in the keto form shown, the N-methyl derivative forms
an equilibrium mixture of keto (156; R = Me) and enol tautomers (157).Il6The
reaction of the pyrrolinone (158) with p-nitrobenzaldehyde unexpectedly yields
compound (159).Il7The product of the action of thiobenzoic acid on (160) is the
spiro-pyrrolinone (161), contrary to a previous report.lls Treatment of p -
hydroxyphenylacetic acid with di-isopropylcarbodi-imide gives the imino-
pyrrolinone (162), which rearranges to the bridged spiro-compound (163) in the
presence of boron trifluoride etherate. '
0
R R
Qo Qo
H
COCF,
(153) (154) R = H
(158) R = Me
noH
ao-jo N N N
Me
Perchloro-2H-pyrrole (164) combines with styrene to yield the rearranged

adduct (165).l2O Irradiation of the enamine (166) in the presence of benzo-
phenone as a sensitizer results in hydrogen transfer from the pyrrolidine ring to
the olefinic group to yield the pyrrole (167).121The direct observation of the
nitrene (168) by i.r. and U.V.spectroscopy has been accomplished.'22
1ndoles.-Formation. Intermediates in the Fischer indole synthesis have been
detected by "N n.m.r. The formation of the indole (170) from
the arylhydrazone (169) indicates preferential migration of the methyl group.124
11' J . T. Baker and S. Sifniades, J. Org. Chem., 1979,44, 2798.
'16 T. Momose, T. Tanaka, T. Yokota, N. Nagamoto, and K. Yamada, Chem. Pharm. Bull., 1979,27,
1448.
'I7 J. M. Rib0 and L. Vinuesa, Tetrahedron Lett., 1979, 1303.
11' U . Kuckllnder and E. J. Edoho, Arch. Pharm. (Weinheim, Ger.), 1980,313,91.
' I 9 K. Gubernator, W. Hofeditz, and H. Plieninger, Chem. Ber., 1980,113, 669.
l Z o P. H. Daniels, J. L. Wong, J. L. Atwood, L. G. Canada, and R. D. Rogers, J. Org. Chem., 1980,
45,435.
lZ1 J. Cossy and J. P. Pete, Tetrahedron Lett., 1978, 4941.
lZ2 P. G. Schultz and P. B. Dervan, J. A m . Chem. SOC.,1980, 102, 878.
Iz3 A . W. Douglas, J. A m . Chem. SOC., 1979, 101, 5676.
lZ4 B. S. Holla and S. Y. Ambekar, Indian J. Chem., Sect. B, 1979, 17, 66.
0 -0 N
I
N
I
>o< N
,c+ CHMeCH,CO,Et
I
!!
Me CHCO2Et (167)
(166) (168)
The preparation of indoles by the benzyne route is illustrated by the base-induced
cyclization of the amino-alcohols (171; R = H or Me) to indole and 3-methylin-
dole, respectively. 125 The photochemical reaction of o-bromo- or o-iodo-aniline
with the enolates (172; R = H, Me, or Pri) leads to indoles (173).1267127 The salt
(174), generated by the action of lithium di-isopropylamide on o-tolyl isocyanide,
serves as a source of diverse indole derivatives: (i) it cyclizes spontaneously to
1-lithioindole, which forms 3-alkyl-indoles on treatment with alkyl halides in the
presence of magnesium iodide,'**" (ii) it reacts with ally1 esters
&J
RC02CH2CH=CH2 (R = alkyl or aryl) to give the ketones (175), which cyclize
Oe
'
- N - N A CMe
02Me
~;;(oH,,:,,NHz
cI H CI H (171)
(1 69) ( 1 70)
0- K+
/
H,C=C
\
R
(172) (173) (174) R = Li
(175) R = COR
to 3-acyl-indoles under the influence of copper(I1) oxide, while hydrolysis yields
3-alkyl- or 3 - a r y l - i n d o l e ~ , ' ~and
~ ~ (iii) it reacts with isocyanates to afford,
ultimately, 3-carbamoyl-indoles.'28' Bis(triphenylphosphine)nickel(II) chloride
catalyses the conversion of the allylaniline (176) into the indole (177).'29 Aryl
azides react with the enamines (178; R2 = Ph or cyclopropyl, R3 = Me or Et)
to yield indolines (179); under the influence of hydrochloric acid, these undergo
elimination and rearrangement to give the indoles ( 180).13"The amino-nitriles
125 I . Fleming and M. Woolias, J. Chem. SOC.,Perkin Trans. 1, 1979, pp. 827, 829.
R. Beugelmans and G . Roussi, J. Chem. SOC.,Chem. Commun., 1979,950.
R. R. Bard and J. F. Bunnett, J. Org. Chem., 1980,45, 1546.
( a ) Y. Ito, K. Kobayashi, N. Seko, and T. Saegusa, Chem. Lett., 1979, 1273; ( b ) Y. Ito, K.
Kobayashi, and T. Saegusa, J. Org. Chem., 1979,44,2030; (c) Y . Ito, K. Kobayashi, andT. Saegusa,
Tetrahedron Lett., 1979, 1039.
M. Mori, S. Kudo, and Y. Ban, J. Chem. SOC., Perkin Trans. 1, 1979, 771.
''O L. Citerio, M. L. Saccarello, and R. Stradi, Synthesis, 1979, 305.
162
or
\ N-CH,
Me
CHMe
/\\CH --+@
Me
( 178) (179)
R' = C1, NO2, or CN
(18l ) , prepared by the combined action of p(benzenesulphony1)aniline and

potassium cyanide o n aromatic aldehydes, cyclize to 3-amino-indoles (182).13'
Condensation of methyl 2-methyl-3-nitrobenzoate with Meerwein's acetal,
Me,NCH(OMe),, gives the enamine (183), which undergoes reductive cycliz-
ation to the indole ester (184).13*The indole derivative (185) is the product of
the complex photochemical reaction of p-nitrobiphenyl with diethyl ma10nate.l~~
The formation of 1-methyl-3-piperidinoindole from N-methylaniline and the
di-iminium salt (186) exemplifies a general synthesis of 1-alkyl-3-amino-
ind01es.l~~
I + phso2@;r
p
hm M e
CO M e
phso 2 n N ,
E :* r
\ N \ N
H H H
(1811 (182) (185)
(183) (184)
The thioacyl-arylhydrazides (187; R = Me, Et, Pr, or Ph) react with phos-
phorus oxychloride to yield the iminium salts (189) by way of the suggested
intermediates ( 188).'3s Quantum yields for the photocyclization (190) + (191)
(R = H, But, Ph, OMe, NO2, efc.) have been d e t e ~ m i n e d . Oxidation
'~~ of the
phenolic amino-ester (192), i.e. a 'dopachrome' reaction, gives the quinone imine
13' M. H. Goghari and A. R. Parikh, J. Inst. Chem., Calcutta, 1979, 51, 143 (Chem. Abstr., 1980, 92,
198 206).
1 3 * G . S. Ponticello and J. J. Baldwin, J. Org. Chem., 1979, 44,4003.
' 3 3 R. Beugelmans, H. Ginsburg, M. T. Le Goff, A. Lecas, J. Pusset, and G . Roussi, Heterocycles, 1979,
12, 811.
134 M. L. Saccarello and R. Stradi, Synthesis, 1979, 727.
13' A. N. Kost, G . A. Golubeva, and A. G . Popova, Khim. Geterotsikl. Soedin., 1979, 344.
136 D. Dopp and E. Brugger, Liebigs Ann. Chem., 1979, pp. 564, 1965.
Fiue-Membered Rings: Other systems 163
(193).'37 Spiro-indolinones (195; R = Me, benzyl, or allyl) result when the

isatoic anhydrides (194) are heated with potassium cyanide.138
Reduction of the diazonium salts (196; Ar = p-MeC6H4, p-C1C6H4, or 2-
biphenylyl) generates the radicals (197), which undergo intramolecular cycliz-
ation to the aminyls (198).'39The hydrazide PhMeNNHCOCH2COMeforms the
naphth[3,2,1 -cd]indole derivative (200) in hot polyphosphoric acid; the reaction
proceeds via the detectable intermediate (199), which undergoes aryl coupling
N'
I1
N
/
Ar
(197)
(201) R (202) R
Me
(200) R = PhCH2
13' H. Auterhoff and W. Wessinger, Arch. Phurm. (Weinheim, Ger.), 1979,312, 794.
13' G. M. Coppola and R. E. Damon, J. Heterocycl. Chem., 1979, 16, 1501.
139 L. Benati, P. Spagnolo, A . Tundo, and G. Zanardi, J. Chem. SOC.,
Perkin Truns. 1, 1979,1536
and N-N bond fission, akin to the benzidine rearrangement.14' The condensa-
tion product (201) of benzylamine and hexakis(bromomethy1)benzene has been
converted into the hexaradialene derivative (202), whose X-ray structure has
been reported. 14' The dibenzotropone (203) reacts with chlorosulphonyl isocyan-
ate to yield not only the expected imine (204) but also the red salt (205).14*
R H H
(206) (207)
(203) R = 0
0
(204) R = NS02CI (205)
Reactions of Indoles. Phase-transfer-catalysed N-acylation o f indole proceeds in
high yield.'43 Indole reacts with thallium(II1) trifluoroacetate to give the thallium
derivative [206; R = Th(CF,CO,),], which is transformed into 3-iodoindole by
the action of potassium iodide.'44 The combined action of the hydrazone
Me2NN=CHCH0 and phosgene on indole affords the salt (206; R =
CH=CH-N=NMe2 Cl-).14sFree-radical amidomethylation of indole by benz-
ylideneaniline in the presence of zinc and acetic anhydride yields (206; R =
CHPhNPhAc). 146 5-Hydroxy-2-methylindole (207; R = O H ) undergoes the
Bucherer reaction with ammonia to give the amine (207; R = NH2).147A useful
general synthesis of compounds containing adjacent amino- and dialkylamino-
groups is illustrated by the conversion of the azide (208) into the morpholino-
derivative (211) by irradiation in the presence of morpholine. The reaction is
thought to proceed by way of the nitrene (209) and the fused azirine (210) (see
N3mco2Et
Kmco2E
Scheme 2).'48
\ N
(208)
H
l?+
\ N
(209)
H
5N&co*Et ' N
(2 10)
H
bC NH,
H
Scheme 2
140
M. J. Kornet, A. P. Thio, and L. M. Tolbert, J. Org. Chem., 1980, 45, 30.
141
J. H. Gall, C. J. Gilmore, and D. D. MacNicol, J. Chem. SOC.,Chem. Commun., 1979, 927.
142
J. Rokach, Y. Girard, and J. G. Atkinson, J. Chem. SOC.,Chem. Commun., 1979,892.
143
V. 0. Illi, Synthesis, 1979, 387.
144
R . A. Hollins, L. A. Colnago, V. M. Salim, and M. C. Seidl, J. Heterocycl. Chem., 1979, 16,993.
145
I. Ipach, H. Lerche, L. Mayring, and T . Severing, Chem. Ber., 1979, 112,2565.
146
A. K. Sheinkman, E. N. Nelin, B. I. Geraskov, and V. P. Marshtupa, Khim. Geterotsikl. Soedin.,
1979, 1137.
147
A. N. Kost, V. I. Terenin, and L. G . Yudin, Khim. Geterotsikl. Soedin., 1979, 786.
148
E. F. V. Scriven, H. Suschitzky, D. R. Thomas, and R. F. Newton, J. Chem. SOC.,Perkin Trans. I,
1979, S3.
The stereospecific formation of cis-indolines by reduction of indoles with

triethylsilane and trifluoroacetic acid has been observed.149 Ozonolysis’ ’* of
3-alkyl-indoles, or oxygenation in pyridine containing copper(1) chloride,’”
affords the keto-amides (2 12), which are converted into 3-hydroxy-3H-indoles
(213) by the action of potassium cyanide.’” The first direct observation of a
1,2-dioxetan derived from an indole has been reported: sensitized photo-oxygen-
ation of 2-t-butyl-l,3-dimethylindoleat -78 “C yields compound (214), which
at -20 “C undergoes ring-opening to the keto-amide (215);’” in contrast,
photo-oxygenation of 2,3-dimethylindole gives the zwitterionic peroxide
(216),lS3and the cyclopenteno-indoles (217; R = Me or MeO) afford benz-
azocinediones (218).’54 The oxindole (219) is produced by the joint action of
dimethyl sulphoxide and hydrochloric acid on indol-3-ylacetic acid.”’ Bromina-
a;:R3 do
tion-hydrolysis of 2,3-dimethylindole leads to the complex heterocycle (220).156
R S NH2
H
\ N \ N Bu‘
(212) R2 = R3 = H Me
(213)
(215) R’ = R2 = Me, R3 = But (214)
a
0 (219)
H
CH2C02H
Photoaddition of dimethyl acetylenedicarboxylate to 1-methylindole affords

the cyclobuteno-indole (221);157”the same type of adduct is formed from
1,3-dimethylindole. The latter reaction yields six other products, which include
the Michael adducts cis- and truns-(222) and the 1:2 ‘adducts’ cis- and trans-
(223).ls7’ There is evidence from i.r., ‘H n.m.r., and mass spectroscopy that
149 A. E. Lanzilotti, R. Littell, W. J. Fanshawe, T. C. McKenzie, and F. M. Lovell, J. Org. Chem., 1979,
44,4809.
F. Sakiyama and T. Nakazawa, Chem. Lett., 1979, 587.
15’ H. Yukimasa, H. Sawai, and T. Takizawa, Chem. Pharm. Bull., 1979,27, 551.
I. Saito, S. Matsugo, and T. Matsuura, J. A m . Chem. SOC.,1979, 101, 4757.
lS3 I. Saito, S. Matsugo, and T. Matsuura, J. A m . Chem. SOC.,1979, 101, 7332.
T. Kametani, T. Ohsawa, and M. Ihara, Heterocycles, 1979,12,913;J. Chem. Res. ( S ) , 1979, 364.
lS5 K. Szabo-Pusztay and L. Szabo, Synthesis, 1979, 276.
lS6 G. I. Dmitrienko, Heterocycles, 1979, 12, 1141.
lS7 ( a ) P. D . Davis and D. C. Neckers, J. Org. Chem., 1980, 45,456; ( b )P. D. Davis, D . C. Neckers,
and J. R. Blount, ibid., p. 462.
166 He teroc y c 1 ic Chemistry
- N
N Me
Me Me E E
(222) 1224)
indole-3-sulphonium ylides (224; R = H, Me, or Ph) undergo covalent hydration
across the 2,3 double-bond.'sx The phase-transfer-catalysed reaction of
chlorofluorocarbene with 3-methylindole yields a mixture of 3-chloro- and
3 -fluoro-4-methylquinoline, 1-(chlorofluoromethyl)-3-methylindole, and 1-
formy1-3-methylind0le.'~~ The novel trimer (225) is obtained by the action of
hydrogen peroxide and titanium(II1) chloride on indole.16' Treatment of the
cycloheptadienoindole (226) with p-chlorobenzenesulphonyl azide produces a
mixture of the aziridine (227) and the spiro-indolines (228) and (229).16' The
oxindole (231) is obtained by treatment of ethyl 3-methylindole-2-carboxylate
Me a
with thionyl chloride, followed by water; the reaction is thought to involve
QQ Me
(227)
NS0,Ar
Ar02SH&
NS0,Ar
+
& Me
NS0,Ar
Me
lS8 K.-H.Park and G . D. Daves, Jr., J. Org. Chem., 1980, 45, 780.
lS9 E. V. Dehmlow and K. Franke, Liebigs A n n . Chem., 1979, 1456.
T. Kaneko, M. Matsuo, and Y. Iitaka, Heterocycles, 1979, 12, 471.
G. A. Bahadur, A. S. Bailey, G. Costello, and P. W . Scott, J. Chem. Soc., Perkin Trans. 1, 1979,
2154.
1,2-migration of the ethoxycarbonyl group in the intermediate (230).'62 Photoly-
sis of the oxindole (232) in methanol yields mainly the ether (234) by way of the
imine (233).163Addition of ethoxyacetylene to the oxindole derivative (235;
Ar = p-BrC6H,) affords a mixture of the Diels-Alder product (236), the ketone
(238), and the ( E ) - and (2)-isomers of the ester (240). The latter compounds
are thought to arise from the spiro-oxindole (237) and the betaine (239),
respectively, as outlined in Scheme 3.'64
Revised structures have been proposed for tyriverdin (2421, the precursor of
Tyrian and for other indole pigments.'66 The nitroxide radical (242;
R = H) reacts with bromine to yield a mixture of the cyclic hydroxylamines
0 COAr
(238)
/
ArCO ArCO
Ac
/ (239) OEt
Scheme 3
162 R. M. Acheson, R. J. Prince, and G. Proctor, J. Chem. SOC.,Perkin Trans. I , 1979, 595.
163 D. Dopp and H. Weiler, Chem. Ber., 1979, 112, 3950.
164 P. Righetti, G. Tacconi, A . Piccolini, M. T. Presenti, G. Desimoni, and R. Oberti, J. Chem. SOC.,
Perkin Trans. I, 1979, 863.
165 C. Christopherson, F. Watjen, 0. Buchardt, and U. Anthoni, Tetrahedron, 1978, 34, 2779.
'66 J. A. Ballantine, J. Chem. SOC.,Perkin Trans. I , 1979, 1182.
168 He terocy c 1ic Chemistry
R I
R' OH
0' (243) a; R' = Br, R2 = H
(241)
(242) b; R' = H, R2 = Br
c; R' = R2 = Br
( 2 4 3 a - ~ ) ; ' ~treatment
~ with dibenzoyl peroxide gives mainly the substitution
product (242; R = PhC02).lh8
1soindoles.-Phthalaldehyde reacts with aromatic amines in the presence of
potassium tetracarbonylhydridoferrate, K[HFe(CO),], to give isoindoles (244)
' ~ ~ pentenyl-isoindole (246)
and isoindolines (245) in variable p r o p o r t i o n ~ .The
forms the intramolecular Diels-Alder adduct (247) on heating.I7'
(244) (245) (246)
4 Systems containing Two Identical Heteroatoms

Dioxoles.-Epoxides (248; R = H, Me, or Ph) are converted into dioxolanones
(249) by the action of carbon dioxide in the presence of SbPhs, SbPh,Br, and
other compounds of quinqueval5nt antimony. 17' Treatment of catechol with the
phosgeneiminium chloride Me2N=CC12 C1- yields the stable benzodioxolium
salt (250)."* Vinylene carbonate (25 1)and cyclopentadienones combine to form
the Diels-Alder adducts (252; R = Me, Et, Pr, or Ph); these afford phenols (253)
on heating or aromatic hydrocarbons (254) on h y d r o l y ~ i s . 1,3-Dioxolan-2-0ne
'~~
(249; R = H) is attacked by trimethylsilyl bromide to give the silyl ether
BrCH2CH20SiMe3and carbon d i 0 ~ i d e . The I ~ ~ reaction of trimethylsilyl azide
with the cyclic orthoester (255) occurs with fission of the indicated bond to afford
the azido-ester N3CH2CH20Ac.'7s1,3-Dioxolenium salts (257; X = Br,, 13, or
ICl,) have been obtained by the action of bromine, iodine, or iodine trichloride,
respectively, on the dioxolan (256).' 7 6 There is evidence that dioxolenium ions
(259; R = p-MeOC6H4 or cyclopropyl) are intermediates in the acid-catalysed
hydrolysis of the methoxy-dioxolans (258)'77 and that the reaction of the
L. Greci, J. Chem. Res. ( S ) , 1979, 204.
M. Colonna, L. Greci, and L. Marchetti, Colloq. Znt. CNRS, 1977, 278 (Radicaux Libres Org.),
p. 455 (Chem. Abstr., 1979,91, 192443).
169 Y. Watanabe, S. C. Shim, H. Uchida, T. Mitsudo, and Y. Takegami, Tetrahedron, 1979, 35, 1433.
17' E. Ciganek, J. Org. Chem., 1980, 45, 1512.
171 H. Matsuda, A . Ninagawa, and R. Nomura, Chem. Lett., 1979, 1261.
'" C. Copeland and R. V. Stick, Aust. J. Chem., 1979,32, 637.
173 E. A . Harrison, Jr., J. Org. Chem., 1979, 44, 1807.
174 H. R. Kricheldorf, Angew. Chem., Int. Ed. Engl., 1979, 18, 689.
175 W. Hartmann and H. G. Heine, Tetrahedron Lett., 1979, 513.
176 A. Goosen and C. W. McClelland, J. Chem. SOC.,Chem. Commun., 1979, 751.
M. Ahmad, R. G. Bergstrom, M. J. Cashen, Y. Chiang, A . J . Kresge, R. A. McClelland, and M. F.
Powell, J. A m . Chem. Sac., 1979, 101, 2669.
norbornane derivative (260) with N-bromosuccinimide to yield the bromo-ester

(262) proceeds via the bromide (261).'78The rigid cisoid dienes (263; X = CH2
or CO) show poor reactivity in Diels-Alder reactions because of the distance
between the termini of the diene
1,2-Dithioles.-A number of charge-transfer complexes of 172-dithiolium
cations, e.g. (264), with tetracyano-p-quinodimethane and tetrathiosquarate salts
have been described."' 3,5-Diphenyl-1,2-dithioliumperchlorate (265) reacts
with methyl cyanoacetate to give the thiapyrone (266); cyanoacetamide, on the
other hand, yields the pyridone (267).181 Photochemical arylation of the
dithiolethione (268) with aryl bromides leads to the arylthio-dithiolium bromides
(269);"' the thione (268) reacts with 4-phenyl-1,2,4-triazoline-3,5-dione to
form the zwitterion (270) with loss of the exocyclic sulphur atom.'83 The
Ph
pXhno Ph
(264) (266) X = S, R = CHZCN (268)

(267) X = N H , R = CN
A. Bazbouz, J . Coste, H. Cristol, and F. Plenat, Tetrahedron Lett., 1979, 11.
H. D. Scharf, H. Plum, J. Fleischhauer, and W. Schleker, Chem. Ber., 1979,112, 8 6 2 .
G . Le Coustumer, J. Amzil, and Y. Mollier, J. Chem. SOC.,Chem. Commun., 1979, 353.
I. Shibuya, Bull. Chem. SOC.Jpn., 1979, 52, 1235.
V. N. Drozd, G . S. Bogomolova, and Yu. M. Udachin, Zh. Org. Khim., 1979,15, 1069.
G . G . Aleksandrov, Yu. T. Struchkov, A. E. Kalinin, A. A. Shcherbakov, G. S . Bogomolova, and
V. N. Drozd, Izu. A k a d . Nauk SSSR, Ser. Khim., 1979,545; V. N. Drozd, V. M. Fedoseev, G. S.
Bogomolova, V. V. Sergeichik, N. M. Semenenko, and A . A . Mandrugin, Zh. Org. Khim., 1980,
16, 198.
Br- ?\
(272) (273)
x-x
I I
x-x
(274) (275) (276)
meso-ionic dithiolium 4-oxide (27 1)is transformed into the hydroxy-isothiazole
(272) by the action of ammonia.184Treatment of 1,2-benzodithiole-3-thione
(273) with tetrachloro-o-benzoquinoneresults in desulphurization to give the
spiro[l,3-benzodioxole-1,2-benzodithiole](274).18' 1,8-Dilithionaphthalene
serves as a source for naphthodithiole (275; X = Y = S) and its selenium (275;
X = Y = Se) and tellurium (275; X = Y = Te) analogues. Sequential reaction
of 1,8-dibromonaphthalene with butyl-lithium, an element of the sulphur Group,
butyl-lithium, and a different such element leads to the mixed systems (275;
X = S, Y = Se), (275; X = S, Y = Te), and (275; X = Se, Y = Te).186The
preparation of the tetracene derivatives (276; X = S, R = M e 0 or But) as
components for charge-transfer complexes has been r e p 0 ~ t e d . The
I ~ ~ selenium
analogue (276; X = Se, R = H) (= Z) forms a series of complexes Z,Br, Z2C1,
ZIo,s,Z(SCN), s, etc., whose conductivities have been measured.18'
1,3-Dithioles.-The 1,3-dithiole-2-thione-4,5-dithiolate(277) is obtained by a
remarkably simple reaction, namely that of carbon disulphide with sodium in
DMF.I8' Acid-catalysed cyclization of the dithiocarboxylic esters (278; R' = Me
or Ph, R2 = H or alkyl) leads to the dithiolethiones (279), with loss of isobut-
ene;"" the propargyl ester (280) similarly yields the methyl derivative (279;
R' = Me, R2 = H) in this reaction."' The action of Dichloramine T on the
thione (279; R' = Ph, R2 = H) affords the tosylimine (281).'92Photolysis of the
thione (279; R' = R2 = H) in an argon matrix produces a mixture of thiiren
(282; R = H), carbon disulphide, and thioketen (H2C=C=S). In contrast,
irradiation of (279; R' = R2 = CF,) gives the thiiren (282; R = CF3) in high
yield, which then decomposes to bis(trifluoromethy1)acetylene and sulphur, no
thioketen derivative being 0 b ~ e r v e d . l ' ~
D. Barillier, Bull. SOC.Chim. Fr., Parti?, 1979, 26.
N. Latif, A . Nada, H. M. El-Namaky, and B. Haggag, Indian J. Chem., Sect. B, 1979, 18, 131.
D. Dauplaise, J. Meinwald, J. C. Scott, H. Ternkin, and J . Clardy, A n n . N. Y. Acad. Sci., 1978,313,
382.
V. Kampars and 0. Neilands, Z h . Obshch. Khim., 1979, 49, 2558.
0. N . Eremenko, S. P. Zolotukhin, A. I. Kotov, M. L. Khidekel, and E. B. Yagudskii, Izv. A k a d .
Naiik SSSR, Ser. Khim., 1979, 1507.
l g 9 G. Steimecke, H. J . Sieler, R. Kirrnse, and E . Hoyer, Phosphorus Sulfur, 1979, 7, 49.
N. F. Haley and M. W. Fichtner, J. Org Chem., 1980, 45, 175.
19' N. F. Haley, Tetrahedron Lett., 1978, 5161.
19* F. Boberg, U. Puttins, and G.-J. Wentrup, Liebigs Ann. Chem., 19'79, 689.
193 M. Torres, A. Clement, W.E. Gunning, and 0. P. Strausz, Nouv. J Chim., 1979, 3, 149.
The meso-ionic 1,3-dithiolium 4-olate (283; R = SMe) exists in equilibrium

with the dimer (284; R = SMe).194Complete regiospecificity is observed in the
lY3-dipolarcycloaddition of styrene to the diphenyl-derivative (283; R = Ph),
which gives only compound (285; R' = H, R2 = Ph); in contrast, methyl acrylate
yields a mixture of (285; R' = CO,Me, R2 = H) and the isomeric adduct (285;
R' = H, R2 = C02Me).195Irradiation of the diphenyl-compound (283; R = Ph)
yields a mixture of 4,5-diphenyl- 1,2-dithiole-3-thione (286) (via the bridged
intermediate shown), sulphur, diphenylacetylene, tetraphenylthiophen, and the
latter's precursor, the dithiin (287). The dithiin is thought to arise from the
dimeric compound (284; R = Ph) by loss of carbon o ~ y s u l p h i d e . ' ~ ~
0.
Dithiobenzoates PhCS2R (R = allyl, propargyl, or benzyl) add to dimethyl

acetylenedicarboxylate to form the dithioles (288) with migration of the group
R.Ig7Piperidine catalyses the addition of acetylenic ketones A r ' C O C z C A r 2 to
4-methy1benzene-ly2-dithiol to give the benzodithioles (289).'98 The reaction of

the acetal BrCH2CH(OEt), with ethanedithiol yields a mixture of the
bis(dithio1an) (291) and derivatives of dithian, which are formed, respectively,
from the cations (290) and (292).199
194 H. Gotthardt, 0. M. Huss, and C. M. Weisshuhn, Chem. Ber., 1979, 112,1650.
195 H.Gotthardt, C. M. Weisshuhn, and B. Christl, Liebigs Ann. Chem., 1979, 360.
196 H. Tezuka, T. Shiba, N. Aoki, K. Iijima, and H. Kato, Kokagaku Toronkai Koen Yoshishu, 1979,
8 (Chem. Abstr., 1980,92, 197 661).
19' V. N. Drozd and 0. A. Popova, Tetrahedron Lett., 1979,4491; V . N . Drozd, Zh. Org. Khim., 1979,
15,1106.
M. N. Basyouni, M. T. Omar, and E. A . Ghali, Synthesis, 1980, 115.
199 G. Giusti, M. Ambrosio, R. FaurC, G . Schembri, E. J. Vincent, and C. Feugeas, C.R. Hebd. Seances
Acad. Sci., Ser. C, 1979, 288,441.
(288) (289)
($-iH1
(290)
-[Q-2~
(291)
C)+ S
(292)
Tetrathiafulva1enes.-Preparations of ever more elaborate compounds of this
class have been announced. Coupling of the dithiolethiones (293; n = 2 or 3) by
means of triethyl phosphite affords the tetracyclic derivatives (294);"' mixtures
of the dithioleselones (295) and (296) give good yields of the crossed product
(297) in this reaction.201The tetraselenafulvalene (299) is obtained by photoly-
sis of 3,4-diphenyl-1,3-diselenole-2-thione (298).'02 Even cyclophanes contain-
ing the tetrathiafulvalene structure have been reported; thus compound (300),
on sequential treatment with methyl iodide, sodium borohydride, and fluoroboric
acid-acetic anhydride, affords a mixture of the tetrathiafulvalenophanes (301)
and (302),203and the paracyclophanes (304) and (305) result from the para-
substituted benzene (303).*04
(299) (297)
MeS SMe
(301) 4,4'-bonded (3041 4-bonded

. I
(302) 5,5'-bonded (303) (305) 5-bonded
*O0 A. F. Garito, M. P. Caca, and M. V. Lakshmikantham, NATO Conf. Ser., [Ser. 61, 1978, 1 (Mol.
Met.), p. 23 (Chem. Abstr., 1979, 91, 156 841).
2"1 M. P. Cava and M. V. Lakshmikantham, A n n . N.Y. A c a d . Sci., 1978,313, 355.
'02 E. Fanghanel and H. Poleschner, 2. Chem., 1979,19, 192.
203 J. Ippen, T.-P. Chu, B. Starker, D. Schweitzer, and H. A. Staab, A n g e w . Chem., Int. Ed. En&
1980, 19,67.
'04 H. A. Staab, J. Ippen, T.-P. Chu, C. Krieger, and B. Starker, Angew. Chem., Int. E d . Engl., 1980,
19.66.
A new class of highly conducting charge-transfer complexes (306; R = H or
Me, X = C1, Br, or I) has been prepared.205 Cyclic voltammetry of the
bis(dithiafulveny1)-derivatives (307) and (308) has been reported.206Oxidation
of the bis(dithio1an) (309) with iodine in the presence of aluminium chloride
yields the crystalline radical cation salt (310).*07
0
Pyrazo1es.-Formation. 3-Amino-4-ethylthio-5-methylpyrazole(311)is formed

by the action of hydrazine on the nitrile MeBrC=C(SEt)CN.’O* Acetylenic
hydrazones R1C~C-C(RZ)=NNHTos (R’ = H, Pr, or Ph; R2 = H or Me)
cyclize in the presence of potassium carbonate to the pyrazoles (312) uia the
N-tosyl derivative^.^'^ Treatment of the (p-chloropheny1)hydrazone (313) of
ethyl 2-furylpyruvate with sulphuric acid affords only 10% of the expected ethyl
3-(2-furyl)indole-2-carboxylate;the main product is the pyrazole (314), formed
presumably by way of the spiro-intermediate shown.210
Ar
Ar
+
Et0,C Et0,C
(314)
Ar = p-CIC6H,
The rates of 173-dipolarcycloadditions of diazoalkanes to alkenes and alkynes
have been determined; electron-attracting substituents in the latter increase the
rate, in accordance with frontier molecular orbital theory, which predicts that
these reactions are controlled by the interaction of the highest occupied
molecular orbital of the diazo-compound with the lowest unoccupied molecular
orbital of the dipolarophile;211the kinetics of the reactions of methyl diazoacetate
or phenyl diazomethanesulphonate, on the other hand, give rise to U-shaped
activity functions, which is also explained by the theory.212Diazomethane or
’05 J. B. Torrance, J. J. Mayerle, V. Y. Lee, and K. Bechgaard, J. A m . Chem. SOC.,1979, 101,4747.
’06 Z. Yoshida, T. Kawase, H. Awaji, and S. Yoneda, Koen Yoshishu-Hibenzenkei Hokozoku Kagaku
Toronkai [oyobi]Koze Yuki Kagaku Toronkai, 12th, 1979, 309.
’07 H. Bock, G. Brahler, U. Henkel, R. Schleckker, and D. Seebach, Chem. Ber., 1980,113, 289.
*08 F. Pochat, Tetrahedron Leu., 1979, 2991.
209 R. Grandi, U. M. Pagnoni, and R. Trave, J. Chem. Res. (S),1979, 327.
’lo B. S. Holla and S. Y . Ambekar, J. Chem. SOC.,Chem. Commun., 1979, 221.
211 L. Fisera, J. Geittner, R. Huisgen, and H . U. Reissig, Heterocycles, 1978, 10, 153.
’12 W. Bihlmaier, R. Huisgen, H. U. Reissig, and S. Voss, Tetrahedron Lett., 1979, 2621.
2-diazopropane yield the l-pyrazolines (315; R = H or Me) with hex-l-ene,

while ethyl diazoacetate affords the 2-pyrazoline (316) in this cycloaddition
reaction.213The enamine (317; NRI2 = pyrrolidino) yields the 1,3-dipolar cyclo-
adducts (318; R2 = C02Me or COPh) with methyl diazoacetate or diazoaceto-
phenone, respectively; in contrast, methyl diazomalonate affords the Michael
adduct 43 19).*14The regiospecific cycloaddition of benzonitrile N-phenylimine,
PhCGN-NPh, to the trans-alkenes (320; R = CN, C02Me, or CBPh) leads to
the pyrazolines (321).215The generation of fluorinated azomethine imines has
been described in a series of articles: the azine (322) adds ethoxyacetylene to

give the 1,3-dipole (323; R = EtO), which slowly rearranges to the pyrazole
(324);216"t-butylethylene similarly yields the pyrazoline (326) uia (325).216b
The
zwitterion (323; R = H), produced from acetylene and the azine (322), adds a
second molecule of acetylene to yield the bicyclic compound (327),216cAn
analogous reaction of benzaldehyde azine with bis(trifluoromethy1)acetylene
leads to the pyrazolopyrazole (328), but the reaction does not stop there:
ring-opening, followed by prototropy, gives the pyrazole (329) as the final
product.216dThe ene-hydrazide (330) is deprotonated to the azomethine imine
R. Huisgen, J. Koszinowski, A. Ohta, and R. Schiffer, Angew. Chem., Znt. Ed. Engl., 1980,19,202.
214 R. Huisgen, H. U. Reissig, and S. Voss, Tetrahedron Lett., 1979, 2987.
215 M. Chiericato, P. Dalla Croce, G . Carganico, and S. Maiorana, J. Heterocycl. Chem., 1979, 16, 383.
2'6 ( a ) F. Hein, K. Burger, and J. Firl, J. Chem. SOC.,Chem. Commun., 1979, 792; ( 6 )K. Burger, H.
Schickaneder, F. Hein, and J. Elguero, Tetrahedron, 1979,35,389; (c) K. Burger, F. Hein, C. Zettl,
and H. Schickaneder, Chem. Ber., 1979, 112, 2609; ( d ) K. Burger, C. Zettl, and F. Hein, ibid., p.
2620.
(329)
E $ ~ / N HMe
H
2 - t.&+,NH
H
E
H
N + EJyrH
\’ F
,N Ac
EH,C Me
(330) (331)
(332)
E = COzMe
(331); this has been trapped as the pyrrolidine (332) by dimethyl fumarate in the
presence of acetic anhydride . 2 1 7
The complex 1-pyrazoline (334) is one of the products of the thermolysis of
the diazocyclohexadienone (333) in diphenylacetylene.21sThe sodium tosyl-
hydrazone (335) decomposes, on heating, to the strained 3H-pyrazole (336);
o n further heating, this yields the benzodiazepine (337).2’9The yellow isomer
of (1,5-diphenylforrnazanyl)glyoxylicacid has been identified as the pyrazolin-
one (338).220Epichlorhydrin forms the pyrazolidin-4-01s (339) when treated
with NW-dial kyl-h ydrazines .221
Reactions of Pyruzoles. The i.r. spectra of pyrazole and eight deuteriated
pyrazoles, in the gas phase and embedded in an argon matrix, have been
0
Ph
(336)
(333) (335)
Bu‘
(334) J
/
217 W. Sucrow, D. Rau, A. Fehlauer, and J. Pickardt, Chem. Ber., 1979,112, 1719.
218 L. Pavlickova and M. Soucek, Collect. Czech. Chem. Commun., 1979,44, 1810.
219
K. L. M. Stanley, J. Dingwall, J. T. Sharp, and T. W. Naisby, J. Chem. SOC.,Perkin Trans. 1 , 1979,
1433.
220 F. A. Neugebauer and H. Fischer, Chem. Ber., 1979,112, 1477.
221 M. J. Kornet and R. Daniels, J. Heterocycl. Chem., 1979, 16, 1485.
recorded.222 A study of the sites of methylation by dimethyl sulphate and
djazomethane and of arylation by a modified Ullmann reaction of a series of
substituted pyrazoles has appeared.223It has been found that there is considerable
nitrodebromination when 4-bromo-pyrazoles are subjected to the action of nitric
acid in 80% sulphuric Photosubstitution of various 1-(p-nitropheny1)-
pyrazoles with cyanide anion yields mixtures of 4-cyano- and 4-carbamoyl-
derivatives; with cyanate anion, 4-formyl-compounds are The
acetylenic pyrazole (340) is deprotonated at the C-methyl group by sodamide in
liquid ammonia but at the N-methyl group by butyl-lithium.226 The photo-
chemical rearrangement of the aminocyanopyrazole (34 1)to the imidazole (342)
supports the hypothesis that the former may be an intermediate in the conversion
of diaminomaleonitrile into adenine.227Macrocycles incorporating four or six
pyrazole rings, e.g. (344), have been prepared from the chloromethyl-pyrazole
(343).228Treatment of 1,4-dinitropyrazole with pyrazole leads to the cine-
substitution product (345).229
Me@;2c1
N'
H
(343) (345)
1-Hydroxy-3,5-dimethylpyrazoleyields the 4-chloro-derivative by the action

of N-chlorosuccinimide; further chlorination leads to the dichloro-4H-pyrazole
N-oxide (346).230The dioxide (347) gives a radical anion on treatment with
potassium in THF;23' piperidinocyclohexene adds to the dioxide to form the
tricyclic compound (348).232 1-Hydroxy-3,5-diphenylpyrazole 2-oxide (349)
222 V. Tabacik, V. Pellegrin, and H. H. Guenthard, Spectrochim. Acta, Part A , 1979, 35, 1055.
223 M. R. Grimmett, K. H. R. Lim, and R. T. Weavers, Aust. J. Chem., 1979,32,2203.
224 K.-C. Chang, M. R. Grimmett, D. D. Ward, and R. T. Weavers, Aust. J. Chem., 1979,32, 1727.
225 P. Bouchet, G. Joncheray, R. Jacquier, and J. Elguero, Tetrahedron, 1979, 35, 1331.
226 A. N. Sinyakov and M. S . Shvartsberg, Zzv. A k a d . Nauk SSSR, Ser. Khim., 1979, 1126.
227 J. Kagan and B. Melnick, J. Heterocycl. Chem., 1979, 16, 1113.
228 A. Fruchier, A. Ramdani, and G. Tarrango, Can. J. Chem., 1979, 57, 1897.
229 P. Cohen-Fernandes, C. Erkelens, C. G. M. Van Eendenburg, J. J. Verhoeven, and C. L. Habraken,
J. Org. Chem., 1979,444156.
230 J. F. Hansen, Y. I. Kim, L. J. Griswold, G. W. Hoelle, D. L. Taylor, and D. E. Vietti, J. Org. Chem.,
1980, 45, 76.
231 G . R . Stevenson, J. F. Hansen, G. Clark, and J. P. Freeman, J, Org. Chem., 1979,44, 3211.
232 J. P. Freeman, M. J. Haddadin, and J. F. Hansen, J. Org. Chem., 1979, 44, 4978.
reacts with phosphorus oxychloride to give a mixture of the 4-chloropyrazoles
(350; R = OH) and (350; R = H).233The meso-ionic pyrazolium oxides (351;
R = H, Ph, or C0,Et) do not undergo cycloaddition reactions; the diazacyc-
lopentadienone (352) functions as a dienophile towards 2,3-dimethylbuta- 1,3-
diene, giving the adduct (353), and as a diene in the reaction with norbornene,
which yields the pyridazine (355) by way of the Diels-Alder product (354).234
The combined action of sulphur and piperidine on antipyrine leads to the
thiiranopyrazolidinone (356).235 4-(Arylmethylene)-5-pyrazolinones(357) react
with the ynamine MeCzXNEt, to yield mixtures of pyrazolo[3,4-b]pyrans
(358) and the adducts (359), which result from spiro-cyclobutene intermediates
(cf. p. 167).236
c
Mel f\ +i /eN
N
OF+
Ph
N 0-
P hN-N,
+ p ph&
N/ ‘0-
I
0-
(346)
0-
I
0-
(347) O-
(348)
0 ; : (
I
Ph\ N P hNN
. w M Mee
N’
R Me N/
Ar
(357) (358) (359)

The dye-sensitized photo-oxygenation of the 4H-pyrazole (360; R = Me)
yields the diketone A C C M ~ ~ A The
C . *diphenyl
~~ analogue (360; R = Ph) under-
goes a stereospecific addition reaction when treated with hydrogen peroxide in
233 J. F. Hansen, Y. I. Kim, and K. A. Merrigan, J. Org. Chem., 1979, 44, 4438.
234 P. J. Fagan, E. E. Neidert, M. J. Nye, M. J. O’Hare, and W.-P. Tang, Can. J. Chem., 1979,57,904.
235 H. Kutlu, Doga, 1979, 3, 71 (Chem. Abstr., 1979,91, 211 321).
236 G . Desimoni, P. Righetti, G . Tacconi, and R. Oberti, J. Chem. SOC.,Perkin Trans. I, 1979, 856.
237 M. E. Landis and D. C. Madoux, J. A m . Chem. SOC.,1979,101,5106.
178 He terocy c 1ic Chemistry
the presence of 1,3-dibromo-5,5-dimethyl-l,3-hydantoin to give solely com-
pound (361).238The action of 2-diazopropane on the 1-pyrazoline-4-thione (362)
affords the isopropylidene derivative (365) by way of the isolable spiro-
thiadiazolidine (363) and the spiro-thiiran (364).239
Ph
Whereas irradiation of the 3H-pyrazole (366) yields the bridged isomer (367)
by electrocyclic ring-closure, thermolysis furnishes a mixture of the 4H-pyrazole
(368) and the lH-pyrazole (369) by competitive migrations of the methyl group
to carbon and nitrogen, re~pectively.~~' Some interesting reactions of 3H-
pyrazoles have been described by Huisgen and Reissig. The action of
diazomethane on the ester (370) yields the lH-pyrazole (372), which is formed
(370) (371) (372)

by loss of nitrogen from the cyclo-adduct (371).24*Compound (373), obtained
from diazomalonic ester and 1-(diethylamino)propyne,adds phenyl isocyanate
to give the imine (375; X = 0)via the adduct (374). The imine decomposes at
100°C, with the formation of the ester (376) and regeneration of phenyl
isocyanate. With phenyl isothiocyanate, however, a catalytic conversion of (373)
into (376) occurs at room temperature, without (375; X = S) being detected (see
Scheme 4).242
A theoretical study of the steric course of thermal extrusion of nitrogen from
the methylene- 1 -pyrazoline (377) has appeared.243The deuteriated derivatives
238 M. E. Landis, R. L. Lindsey, W. H. Watson, and V. Zablel, J. Org. Chem., 1980, 45, 525.
239 R. J. Bushby and M. D. Pollard, J. Chem. SOC.,Perkin Trans. 1, 1979, 2401.
240 W. J. Leigh and D. R. Arnold, Can. J. Chem., 1979,57, 1186.
241 R. Huisgen and H. U. Reissig, J. Chem. SOC.,Chem. Commun., 1979, 568.
242 H. U. Reissig and R. Huisgen, J. A m . Chem. SOC.,1979,101, 3648.
243 C.D . Duncan, E. A. Halevi, and C. Trindle, J. A m . Chem. SOC.,1979, 101, 2269.
E = C02Me
Scheme 4
(378; R’ = H, R2 = Me) and (378; R’ = Me, R2 = H) yield the methylenecyc-
lopropanes (380) and (381) in different proportions; the implications of these
findings have been discussed with reference to the biradical intermediates
(379).244Iminocyclopropanes (383; R = alkyl) have been obtained by heating
the pyrazolines (382).245The amino-2-pyrazoline (384) gives rise to a stable
diazonium
R2
D H
H D
R3 D
(377) R’ = R2 = R3 = H (379) (380) (381)
(378) R3 = D
A number of stereospecific lY3-dipolar cycloaddition reactions of the

azomethine imine (385) with olefins have been The dipole (386),
generated as shown, has been trapped as the cyclo-adduct (387) to dimethyl
~ ~ betaine (389) is formed in the reaction of 1,2-diphenyl-
f ~ m a r a t e . *The
-
+I’ 0
p:Ph 0’’
P NN / P h x p N /L e
N/
Ph Ph Me
(388) (389) (390)
244 R. J. Crawford, Colloq. Int. CNRS,1977,278 (Radicaux Libres Org.), p. 199 (Chem. Abstr., 1979,
91, 174 569).
245 H. Quast, A, Fuss, and A. Heublein, Angew. Chem., Int. Ed. Engl., 1980, 19, 49.
246 M. V. Gorelik, S. P. Titova, m d V. I. Rybinov, Zh. Org. Khim., 1979, 15, 1563.
247 H. Dorn, R. Ozegowski,and E. Grundemann, J. Prakt. Chem., 1979, 321,555, 5 6 5 .
248 G. LeFbvre and J. Hamelin, Tetrahedron Lett., 1979. 1757.
pyrazolidine-3,s-dione (388) with phenyl i o d o ~ o a c e t a t eSequential

.~~~ treatment
of the pyrazolidinethione (390; Ar = p-C1C6H4,X = S) with methyl iodide and
hydrogen telluride affords the tellurone (390; X = Te), which is highly sensitive
to moisture.2s0
1ndazoles.-N-Aryl-o-azidobenzamides (391) yield the chloro-indazoles (392)
on treatment with thionyl chloride.2s1 The formation of 1,3-diphenylindazole
(393) by the action of trifluoromethanesulphonic anhydride on benzaldehyde
N‘N’-diphenylhydrazone was discovered by using a computer-assisted synthetic

design program.252Sodium hydroxide converts the cyclohexadienone phenyl-
hydrazone (394) into the indazole (3951, possibly by way of the intermediate
shown in Scheme 5.2s3
C1,HC Ph
\ + /
CI,HC / y h
/ \ -H’
5M e
-_
e N HN H -2
---+HCI Me 6 - N
M e aN N H P h
(394) Scheme 5 (395)
3-Diazoindazole is reduced to indazole by the combined action of titanium(II1)

chloride and iron(I1) ammonium ~ u l p h a t e . ~ ~ ~
1midazoles.-Formation. Several new syntheses Df imidazoles from isocyanides
have been reported: these include the formation of 1-alkyl-imidazoles (396)
by the action of primary amines on 2-isocyano-2-tosylstyrene, PhCH=C-
(NC)TOS,~” the cyclization of the enamine Me2NCH=C(NC)C02Me to com-
pound (397) in the presence of methyl iodide,2s6and the preparation of the ethers
or thioethers (398) from isocyano-cyanides R’CH(NC)CN by their reaction with
alcohols or thiols R2XH, re~pectively.~” Aromatic aldehydes are converted into
2-aryl-4,s-dichloroimidazoles(399) by the combined action of cyanogen and
hydrochloric 5-Acetyl-4-methylimidazole (400) results when form-
amido-acetylacetone, Ac,CHNHCHO, is heated with formamide and formic
Exhaustive chlorination of tetramethyldithio-oxamide leads to the tri-
chloro-imidazolium cation (401).260
249 0. Ya. Neiland and B. Ya. Adamsone, Khim. Geterotsikl. Soedin., 1979, 1695.
250
K. A. Lerstrup and L. Henriksen, J. Chem. SOC.,Chem. Commun., 1979, 1102.
25’ M. Ardakani, R. K. Smalley, and R. H. Smith, Synthesis, 1979, 308.
252 R. Barone, P. Camps, and J. Elguero, A n . Quim., 1979,75,736 (Chem. Abstr., 1980,92, 163 397).
25’ T. G . Miller and R. C. Hollander, J. Org. Chem., 1980, 45, 1334.
254
B. Stanovnik, M. TiSler, M. Kocevar, B. Koren, M. Bester, and V. Kermavner, Synthesis, 1979,
194.
255 A. M. Van Leusen, F. J. Schaart, and D. Van Leusen, Recl. Trav. Chim. Pays-Bas, 1979,98, 258.
256 U. Schollkopf, P. H. Porsch, and H. H. Lau, Liebigs Ann. Chem., 1979, 1444
257 U. Schollkopf and K. Hantke, Liebigs Ann. Chem., 1979, 1602.
258 D. Gunther and D. Bosse, Angew. Chem., Int. Ed. Engl., 1980, 19, 130.
25q E. P. Krebs and E . Bondi, Helv. Chim. Acta, 1979, 62,497.
260
Z. Janousek, F. Huys, L. Rene, M. Masquelier, L. Stella, R. Merenyi, and H. G . Viehe, Angew.
Chem., Int. Ed. Engl., 1979, 18, 616.
(396) (397) (398) R2 = OR or SR (399) (401)

(400) R' = Ac, R2 = Me
X-Ray analysis shows that the condensation product of p,p'-dichloro-
benzil with methylguanidine is the 4H-imidazole (402; Ar = p-C1C6H4).261
The allene Et,C=C=CHCN reacts with 1,2-diaminoethane at 300 "C to
give the imidazoline (403; R = Et2CH) by elimination of acetonitrile
from an intermediate imidazolidine.2h2The NN'-diacyl-1,2-diaminoethanes
Me(CH2),CONHCH2CH2NHCO(CH2),Me (n = 8 , 10, 12, 14, or 16) afford
high yields of the imidazolidines [403; R = Me(CH2),] under the influence of
phenyl phosphorodiamidate, PhOP(0)(NH2)2.263 The enediamine (404; R2N =
morpholino) condenses with the N2-chloro-acylamidine PhCONHCPh=NCI to
yield the trans -imidazoline (405).2"4Imidazoline N-oxides (407) are obtained by
the action of phosphorus pentachloride on the aximes (406; Ar = p-MeC& or
p-C1C6H4).26s The preparation of the stable nitroxide (408)has been described.266
R2N
O RN
H
(404)
H 2-3
R2 N Bz
N Ph
(403)
(405)
H
O- Bu'N=C
Ph-C-CH,NHAr
II
NOH
(406)
+ ?Y N
Ar
Me ,?j
N
I
Me
(407) 0'
(408)
The chloro(ethoxycarbony1)iminium chloride EtO,CCl=I?HMe C1- is a ver-
satile intermediate for the synthesis of heterocycles; with phenylurea, for
example, it affords the imidazolinedione (409).267Treatment of the complex
azine (CF3)2C=N-C(NMe2)=N-N=C(CF3)2with t-butyl isocyanide yields
the imidazoline derivative (410).268 Mixtures of meso- and DL-tetra-
arylimidazolidinethiones (411) are obtained by successive treatment of Schiff's
bases Ar' CH=NAr2 with sodium and carbon d i ~ u l p h i d eThe
. ~ ~acid-catalysed
~
26 I
H. Takayanagi, H. Ogura, K. Matsuzaki, K. Kitajima, and T. Nishimura, Bull. Chem. SOC.Jpn.,
1979,52,3358.
262 S. R. Landor, P. D. Landor, Z. T. Fomum, and G . W. B. Mpango, J. Chem. SOC.,Perkin Trans. 1,
1979,2289.
2h3 R. N. Butler, C . B. O'Regan, and P . Moynihan, Tetrahedron Lett., 1979,3117.
264 L. Citerio, M. L. Saccarello, R. Stradi, and B. Gioia, J. Chem. Res. ( S ) , 1979, 347.
265 T. Kiersznicki and A. Rajca, Pol. J. Chem., 1979, 53, 1147.
266 I. A. Grigorev, G . I. Shchukin, A. G. Druganov, and L. B. Volodarskii, Izu. Sib. Old. Akad. Nuuk
SSSR, Ser. Khirn. Nuuk, 1979,80 (Chem. Ahstr., 1979,91, 5159).
267 D. Bartholomew and I. T. Kay, Tetrahedron Lett., 1979, 2827.
268 K. Burger, F. Hein, and J. Firl, Chem.-Ztg., 1979,103, 264.
769 K. N. Mehrotra and G . Prasad, Indian J. Chem., Sect. B,1979, 17, 405.
reaction of methylphenylglyoxal with NN'-dimethylurea yields the spiro-

compound (412).270
Reactions of Imidazoles. The action of sodamide on the chloro(ethyny1)-
imidazole (413; R' = C1, R' = H) results in the formation of the isomer
(413; R' = H, R' = Cl); similar transhalogenations have been observed for
chloro(ethyny1)-pyrazoles and -1,2,4-tria~oles.*~'The imidazolium salt (414)
undergoes base-induced ring-expansion to the pyrazine derivative (415).272
2,4,5-Tribromo-1 -methylimidazole reacts with xenon difluoride to give the
imidazolidinetrione (416).273Low-temperature 'H n.m.r. studies of the sensitized
photo-oxygenation of imidazoles (417; R', R', R3 = H or Me) give direct
evidence for the formation of unstable endo-peroxides (418);2742-methyl-4,5-
diphenylimidazole yields the peroxy-derivative (419) in this reaction.27sIrradia-
tion of the N-oxide (420) produces the diamine (422) by way of the oxaziridine
(421).276
C02Me CHO
0- Ph
P h Nr g h
ph&o
N Ph
Ph Ph Ph
(420) (421 ) (422)
The Ns,,N'O-methenyltetrahydrofolate model (423) can transfer a formyl
equivalent to nucleophiles; p-chlorophenylmagnesium bromide, for example, is
270 A. R. Butler, I. Hussain, and E. Leitch, J. Chrm. SOC., Perkin Trans. 2, 1980, 160.
271 A. N. Sinyakov and M. S. Shvartsberg, Izc. Akad. Nauk SSSR, Ser. Khim., 1979, 2306.
272 P. Dalla Croce, M. Ioannisci, and E. Licandro, J. Chem. SOC.. Perkin Trans. I, 1979, 330.
273 L. N. Nikolenico, N. S. Tolmacheva, and L. D. Shustov, Z h . Obshch. Khim., 1979, 49, 1429.
274 H.-S. Ryang and C . S. Foote, J. A m . Chern. Sac., 1979, 101,6683.
275 M. L. Graziano, M. R. Iesce, and R. Scarpati, J. Chem. SOC.,Chem. Commun., 1979,7.
276 A. D. Woolhouse, Aust. J. Chem., 1979, 32,2059.
converted into p-chl~robenzaldehyde.~~~ The stable nitroxide radical (424)can
be methylated with diinethyl sulphate; the resulting salt is deprotonated by alkali
to form the methylene-derivative (425),which undergoes acetylation and diazo-
coupling at the indicated The X-ray structure of the nitroxyl N-oxide
(426;R = Ph) has been determined.279The bromomethyl analogue (426;R =
BrCH,) undergoes normal nucleophilic displacement reactions with potassium
azide, iodide, phthalimide, acetate, and thiocyanate; with hydroxylamine,
however, the N-hydroxy-"-oxide (427)is obtained.280The nucleophilic carbene
(428)combines with tetramethyl allenetetracarboxylate to yield the stable dipole
(429),which is a nitrogen analogue of trimethylenemethane.281
Me
(423)
0-
+/
Me 2cJ
R-N
I
Me2
0.
(426)
(427) R = CH=NOH (429) E = C02Me
Benzimidazo1es.-The synthesis of the sexidentate donor ligand (430)from
o-phenylenediamine and ethylenediaminetetra-acetic acid, and its complexing
properties, have been described.282The o-nitro-tosylamides (431;R = Me or Ph)
cyclize under the influence of sodium methoxide; the product exists as an
equilibrium mixture of benzimidazole N-oxide (432)and the corresponding
N-hydroxyben~imidazole.~"~ The blue pigment formed from 9,lO-phenanthra-
quinone, guanidine, and l-naphthol in the presence of alkali has been assigned
structure (433).284 The major product of the action of dichlorocarbene on
benzimidazole is tris(benzimidazol-2-yl)methane.2s"Arenediazonium salts are
converted into aryl azides by their reaction with 1 -aminobenzimidazole.286
Treatment of l-methylbenzimidazole with methyl phenylethynyl ketone leads to
the ring-expanded benzodiazocinone (434).287
211
U . K. Pandit and H. Bierangel, J. Chem. SOC.,Chem. Commun., 1979,117.
278 L. B. Volodarskii, V. A . Reznikov, and V. S. Kobrin, Zh. Org. Khim., 1979, 15, 415.
279 A. A. Shevyrev, L. A . Muradyan, and V. I. Simonov, Pis'ma Zh. Eksp. Teor. Fiz., 1979,30, 107
(Chem. Abstr., 1979, 91, 192 262); A. A . Shevyrev, G. S. Belikova, L. B. Volodarskii, and V. I.
Simonov, Kristallografiya, 1979,24,787.
I. A. Grigorev, V. V. Martin, G. I. Shchukin, and L. B. Volodarskii, Izv. A k a d . Nauk SSSR, Ser.
Khim., 1979, 2711.
R. Gompper and U. Wolf, Liebigs A n n . Chem., 1979, 1406.
282 H. M. J. Hendriks, W. 0.Ten Bokkel Huinink, and J . Reedijk, Red. Trav. Chim. Pays-Bas, 1979,
98,499.
283 J. Machin and D. M. Smith, J. Chem. SOC.,Perkin Trans. I, 1979, 1371.
284 T. Sakaguchi, S. Tanabe, and T. Ohya, Yakugaku Zasshi, 1979,99, 290.
H. Singh and P. Singh, Indian J. Chem., Sect. B, 1979, 17, 1.
286 V. V. Kuzmenko. V. N. Komissarov, and A . M. Simonov, Zh. Org. Khim., 1979, 15, 1108.
R. M. Acheson, J. D. Wallis, and J. Wollard, J. Chem. SOC.,Perkin Trans. I , 1979, 584.
Tos
R2NCH2CH2NR2
(430) R = C H , N
q N 3 3
H
Me'
OACH2':""
NO,
(431)
I
0-
-N
(434)
3 a H -Benzimidazoles are thought to be intermediates in reactions of benz-
imidoylnitrenes, discovered by Rees and his co11eagues.288These nitrenes, e.g.
(438), are generated by photolysis of the corresponding N-aryl-benzimidoyl-
sulphimide (435) or -tetrazole (436), or by flash vacuum pyrolysis of the latter or
of the 4-aryl- 1,2,4-oxadiazolin-5-one (437). In each case, the diaryl-carbodi-
imide (439) is formed as a result of a Curtius-type rearrangement of the nitrene,
together with the cyclopentapyrimidine (4 11). In the pyrolysis experiments, small
amounts of the isomeric dimethyl-2-phenylbenzimidazolederivatives (442) and
(443) are also isolated. It has been suggested that the formation of these products
proceeds by cyclization of the nitrene to the 3aH-benzimidazole (440), which
rearranges to the cyclopentapyrimidine by consecutive [ 1,5] vinyl and [1,5]
imidoyl shifts, and to the benzimidazoles by a series of [1,5_]or [1,9] methyl shifts,
as shown in Scheme 6. In the photolysis of the tetrazole derivative (444), which
yields 1-methoxycarbonyl-2-phenylbenzimidazole(446) uia the nitrene (445),
there is evidence that the ring-closure occurs about equally at the blocked and the
unblocked positions.
5 Systems containing Two Different Heteroatoms

Oxathioles and 0xaselenoles.-The phenacyl dithiocarbamate
PhCOCH2SC(S)NMe2 is tranformed into the 1,3-oxathiolium salt (447) by
treatment with dimethyl sulphate followed by sodium p e r ~ h l o r a t eMonothio-
.~~~
benzil forms tetraphenyl-1,3-oxathiole(448) by the action of diazodiphenyl-
methane.290The thioamide (449) reacts with a-bromopropiophenone to yield the
methylerieoxathiole (450).291The action of pyridine hydrochloride on S-(2-
methoxyphenyl) NN-dimethylthiocarbamate results in the 1,3-benzoxathiol-2-
one (451).292o-Benzoylbenzenesulphonyl chloride (452) exists as an equilibrium
288 T. L. Gilchrist, C . J. Moody, and C. W. Rees, J. Chem. Soc., Perkin Trans. 1, 1979, 1871; T. L.
Gilchrist, P. F. Gordon, D . F. Pipe, and C. W. Rees, ibid., 1979, 2303; C. W. Rees, Pure A p p l .
Chem., 1979,51,1243.
289 Y. Ueno and M. Okawara, Synthesis, 1979, 182.
290 C. Bak and K. Prafcke, Chem. Ber., 1979,112, 2744.
291 H. Dehne and P. Krey, 2. Chem., 1979, 19, 251.
292 J. T. Traxler, J. Org. Chem., 1979, 44, 4971.
V
X”,
(435) (436)X-Y = N=N

1 J (437)x-Y = c-0
\ Me N.
- oM:=C=NPh
0
II
(439)
[l,S] imidoyl shift

[1,5] vinyl shift &>Ph [1,5] proton sh:
N
Me Me
(441)
[1,5] Me shift
(443)
Scheme 6
(444) (445) (446)

mixture, containing 30% of the cyclic isomer (453).293The product of the reaction
of selenium dioxide with dimedone has been re-assigned the oxaselenole struc-
ture (454).294
The 2-alkoxy-1,3-benzo-oxathioles(455), prepared from the corresponding
benzo-oxathiolium fluoroborates by the action of alcohols R 2 0 H in the presence
of sodium hydrogen carbonate, behave as masked esters R1C02R2,which they
293 D. Balode and R. Valters, Zh. Org. Khim., 1979, 15, 876.
294 T. Laitalainen, T. Simonen, M. Klinga, and R. Kivekaes, Finn. Chem. Lett., 1979, 145 (Chem.
Abstr., 1980, 92, 163 902).
I
acoph
Ph c1
asx::
(451) R'R2 =; 0
0
S0,CI = @O
0 2
(455) R' = alkyl or aryl, R2 = 0 alkyl (452) (453)
yield on hydrolysis.295The conformation of the cyclic difluorosulphurane (456)

has been and the X-ray structure of the anhydride (457) has been
d e f e ~ m i n e d . ~4,4-Dimethyl-1,3-oxathiolan
~' 3,3-dioxide (458; R = H) serves as
a carbonyl-anion equivalent; thus successive treatment with butyl-lithium and
benzyl bromide yields (458; R = PhCH,); this decomposes, on heating, to a
mixture of 2-methylpropene, sulphur dioxide, and phenyla~etaldehyde.~~~
Flash vacuum pyrolysis of S-phenyl-l,2-oxathiolan 2-oxide (459) affords
phenylcyclopropane with loss of sulphur the 1,2-oxathiolan-5-one
2-oxide (460) yields tetraphenylethylene, carbon monoxide, and sulphur diox-
ide,300and 2,4-diphenyl-l,3-oxathiolan-5 -one (461) gives 2,3-diphenylthiiran
(462).30'The alcohols (463; n = 1, 2, or 9), obtained from the lithio-derivative
(458; R = Li) and cycloalkanones, form homologous 1-hydroxy-cycloalkanones
(464) on t h e r m o l y ~ i sThe
. ~ ~ X-ray
~ analysis of 4,4'-spirobis[4-selena-4-butanol-
ide] (465) has been d e ~ c r i b e d . ~ " ~
Isoxazo1es.-Formation. 0-Alkyl-hydroxylamines react with diketen to yield
3-hydroxy-5-methylisoxazole(466), with elimination of the a l k o x y - g r o ~ p s . ~ ~ ~
The action of hydroxylamine on the unsaturated ketones ArCOCH=CHCCl,
under basic conditions leads to (trichloromethy1)isoxazolines (467); in the
presence of acids, however, 1,2-0xazin-6-ones (468) are formed.305 Silyl
295 G . Aimo, I. Degani, and R. Fochi, Synthesis, 1979, 223.
296 L. D . Martin, E. F. Perozzi, and J. C. Martin, J. A m . Chem. SOC.,1979,101, 3595.
297 W. Walter, B. Krische, and G. Adiwidjaja, Liebigs Ann. Chem., 1980, 14.
298 G. W. Gokel, H. M. Gerdes, D . E. Miles, J. M. Hufnal, and G. A. Zerby, Tetrahedron Lett., 1979,
3375.
299
T. Durst, J. D . Finiay, and D . J. H. Smith, J. Chem. Soc., Perkin Trans. 1, 1979, 950.
300 H. Kohn, P. Charumilind, and S. H. Simonsen, J. A m . Chem. Soc., 1979,101, 5431.
T. B. Cameron and H. W. Pinnick, J. A m . Chem. Soc., 1979,101, 4755.
302 G. W. Gokel and H. M. Gerdes, Tetrahedron Lett., 1979, 3379.
303 B. Dahlen and R . Lindgren, Acra Chem. Scand., Ser. A , 1979,33, 403.
304 H. Fukumi, K . Oohata, and K. Takada, Heterocycles, 1979, 12, 1297.
305 H. Voigt, 2. Chern., 1980, 20, 19.
ph\ " Ph
(473) R' = NO2, R2 = R3 = Me
nitronates RCH=&(OSiMe,)--O-, prepared from nitroalkanes RCH2N02

and trimethylsilyl chloride, add to acrylonitrile to form the isoxazolidines (469),
which are converted into silyloxy-isoxazolines (470) by potassium fluoride;
treatment with toluene-p-sulphonic acid then gives isoxazoles (47 l), with eli-
mination of trirnethyl~ilanol.~'~ Isoxazoline N-oxides (472) are produced by the
action of silver nitrate on alkali-metal salts of aryl-nitroalkanes ArCH2N0,.307
Oximes of a-nitro-ketones ArC(=NOH)CH2N02 react with aldehydes or
ketones to form nitro-isoxazolines; acetone, for instance, yields the dimethyl
derivatives (473).308The action of dichloromesitonitrile oxide on phenoxyallene
affords a mixture of stereoisomeric 1: 1 adducts (474) and the 2 : 1 adduct
(474) (475)
306 S. C. Sharma and K. Torsell, Acta Chem. Scand., Ser. B, 1979,33,379.

307 K. Fukunaga, K. Hamanaka, andM. Kimura, Bull. Chem. SOC.Jpn., 1979,52,1543.
'O8 L. A. Demina, G. Kh. Khisamutdinov, S. V. Tkachev, and A. A. Fainzilberg, Zh. Org. Khim., 1979,
15, 735.
(475).309 The Reformatskii reaction of C-methyl-N-phenylnitrone,

+
MeCH=N(Ph)-0-, with ethyl bromoacetate furnishes the isoxazolidinone

(476).310The intramolecular 1,3-dipolar cycloaddition of the nitrone (477)results
in the regio-isomers (478) and (479).311 In the reaction of C,N-diphenylnitrone
with allene, the expected product (480) is accompanied by the pyrrolidinone
(481) and the benzazepinone (482); the latter are thought to arise from the
intermediates shown in Scheme 7."'
Ph
Scheme 7 (482)
Reactions of Isoxazoles. The chloroisoxazolium salt (483) activates carboxylic
acids for condensation with alcohols and amines.313The Lewis-acid-catalysed
addition of ammonia to the unsaturated acid (484) yields (*)-homoibotenic acid
(485), with concomitant d e r n e t h y l a t i ~ n . 5-Amino-3,4-dimethylisoxazole
~~~
(486) couples with p-nitrobenzenediazonium chloride not only at the amino-
group but also at C-4, to give the isoxazolinone (487;Ar = P - N O ~ C ~ H The ~).~'~
isoxazolylcarbene (488) has been generated by heating the corresponding
diazomethyl Whereas irradiation of the styryl-isoxazole (489)
either as a solid or adsorbed on silica gel produces mainly the head-to-tail
cyclo-adduct (490), irradiation of a solution gives a 1 : 1 mixture of compound
(490) and the head-to-head dimer (491).317 16-Methyl-(3,5)[1l]isoxazolophane
309 G . Zecchi, J. Org. Chem., 1979, 44, 2796.
310 H. Starnrn and H. Steudle, Tetrahedron, 1979, 35, 647.
311 T. Kusumi, S. Takahashi, Y. Sato, and H. Kakisawa, Heterocycles, 1978, 10, 257.
312 J. J. Tufariello, S. A. Ali, and A. 0. Klingele, J. Org. Chem., 1979, 44, 4213.
3 1 3 K. Tornita, S. Sugai, T. Kobayashi, and T. Murakami, Chem. Pharm. Bull., 1979,27, 2398.
3 ' 4 J. J. Hansen and P. Krogsgaard-Larsen, J. Chem. SOC., Chem. Commun., 1979, 87.
31s C. Siv, G . Vernin, and J. Metzger, Helv. Chim. Acta, 1979, 62, 1570.
3 1 6 S. I. Hayashi, M. Nair, D . J. Houser, and H. Shechter, Tetrahedron Lett., 1979, 2961.

317 D . Donati, M. Fiorenza, and P. Sarti-Fantoni, J. Heterocycl. Chem., 1979, 16, 253.
/
* (488) (491)
(492) (493) (494)
(492),prepared from 2-methylcyclotetradecane-1,3-dioneand hydroxylamine, is

converted into the azirine (493)by the light from a mercury lamp; on further
irradiation at 254 nm, (493)rearranges to the oxazolophane (494).318
Treatment of the chloromethyl-2-isoxazoline (495)with a base yields a mixture
of the fused cyclopropane (496)and conjugated and unconjugated oximes (497)
and (498).319 The rings of 2-isoxazolines are opened by lithium di-isopropylamide
to give sterically homogeneous oximes, in which the original configuration of the
carbon-nitrogen double-bond is retained.32"The action of lithium aluminium
hydride on the diphenyl-derivative (499)yields 95% of the amino-alcohol (500)
with the configuration shown; other reducing agents are less s t e r e o ~ e l e c t i v e . ~ ~ ~
Irradiation of a solution of 3-( p-cyanophenyl)-2-isoxazoline(501) in benzene
affords a mixture of the cleavage product (502),the fission product p-di-
cyanobenzene, the rearranged oxazoline (503),and the cyclo-adduct (504).322
318 S. Albanesi, A. Marchesini, and B. Gioia, Tetrahedron Lett., 1979, 1875.

319 H. Grund and V. Jaeger, J. Chem. Res. ( S ) ,1979,54.
320 H. Grund and V. Jaeger, Liebigs Ann. Chem., 1980, 80.
321 V. Jaeger and V. Buss, Liebigs Ann. Chem., 1980, 101.
322 T. Kumagai, Y. Kawamura, K. Shimizu, and T. Mukai, Koen Yoshihu-Hibenzenkei Hokozoku
Kagaku Toronkai [oyobi]Kozo Yuki Kagaku Toronkai, 12th, 1979, 317 (Chem. Abstr., 1980,92,
197 557).
+ + ArCN
The isoxazolinone (505) undergoes ring-expansion to the 1,3-oxazinone (506)

in the reaction with phenyl isocyanate.323Pyrolysis of the oximino-isoxazolinones
(507;R=Me or Ph) gave fulminic acid, HCNO, which was trapped at -196 0C.324
(505) (506) (507) (508)

2,1-Benzisoxazoles.-The action of thionyl chloride on methyl a-nitromandelate
leads to the ester (508).325Nuclear chlorination also occurs in the reaction of the
benzisoxazole (509), which yields 2-amino-3,5-dichlorobenzophenone(5 1l),by
way of the sulphinylamine (SlO), as The kinetics of the reaction of
sodium methoxide with 6-chloro-3-methyl-7-nitro-2,1-benzisoxazole, which
involves the benzisoxazole-benzofuroxan rearrangement (512)+ (513), have
been
Ph
Me
323 F. Risitane, G . Grassi, F. Foti, F. Caruso, and G. Lo Vecchio, J. Chem. SOC.,Perkin Trans. 1, 1979,
1521.
324 C. Wentrup, B. Gerecht, and H. Briehl, Angew. Chem., Int. Ed. Engl., 1979, 18, 467.
325 T. J. McCord, D. R. Smith, J. K. Swan, A. M. Goebel, D. E. Thornton, C. C. Yakshe, and A. L.
Davis, J. Heterocycl. Chem., 1979, 16, 1249.
326 R. C. Boruah, J. S. Sandhu, and G . Thyagarajan,J. Heterocycl. Chem., 1979, 16, 1087.
327 L. Di Nunno and S. Florio, Gazz. Chim. Itul., 1978, 108, 607.
0xazoles.-Formation. w-Diazoacetophenone reacts with benzonitrile in the
presence of trifluoromethanesulphonic acid to give 2,5-diphenyloxazole (514).328
Bi-, ter-, and quater-oxazoles have been synthesized from a-metallated iso-
cyanides; thus lithiobenzyl isocyanide (PhCHLiNC) and dimethyl oxazole-3,4-
dicarboxylate afford compound ( 5 15).329Stable methylene-oxazolines (516;
R = Me or Ph) are obtained by heating the imines HN=C(P~)OCHRCECH.~~'
The fluorinated oxazoline (518) results from the action of benzonitrile on the
oxiran ( 5 17), and also from the reaction of bis(trifluoromethy1)carbene with the
benzoylimine (CF3)2C=NCOPh.331Treatment of 2-acylamino- 1-aryl-alkan-1-
01s (519) under the conditions of the Pictet-Gams reaction, i.e. with phosphorus
pentoxide in boiling toluene or xylene, results in cis- and trans-2-oxazolines
( 520), rather than isoquinolines, as claimed previously.332The spiro-oxazolines
(521; R = Me or Ph) are formed when the lithiated di-isocyanide
CN-CH2CH2CHLi-NC is treated with acetone or benzophenone, respec-
t i v e ~ ~ . ~ ~ ~
P h c ) Ph
0
(514)
R1 H
\ / H N
T
F F o
The action of phosgene or thionyl chloride on the N-(benzyl-

oxycarbony1)amino-acids PhCH202CNHCHRC02H (R = PhCH2 or Pr')
yields 2-oxazolin-5-ones (522), contrary to a previous Numerous
3-oxazolin-5-ones (523; R', R2, R3 = alkyl or Ph) have been prepared from
hydroxylamino-acids HONHCHR1C02H and ketones R2COR3.335The revised
structure (524) has been established by X-ray diffraction for the product of the
reaction of ethyl diazoacetate with di-isopropylcarbodi-imide,catalysed by salts
of transition Treatment of the diazomethylphosphoryl compound
(MeO),P(0)CHN2with aroyl isocyanates affords the 2-oxazolin-4-ones (525).337
328
W. T. Flowers, G. Holt, and P. P. McCleery, J. Chem. SOC.,Perkin Trans. 1, 1979, 1485.
329
K. W. Henneke, U. Schollkopf, and T. Neudecker, Liebigs Ann. Chem., 1979,1370.
330
L. E. Overrnan, S. Tsuboi, and S. Angle, J. Org. Chem., 1979,44,2323.
331
Z. V. Safronova, L. A. Sirnonyan, Yu. V. Zeifman, and N. P. Gambaryan, Izv. Akad. Nauk SSSR,
Ser. Khim.,1979, 1826.
332
N. Ardabilchi, A. 0. Fitton, J. R. Frost, F. K. Oppong-Boachie, A . H. b.A. Hadi, and A. b.M.
Sharif, J. Chem. SOC., Perkin Trans. I, 1979, 539.
333
U. Schollkopf, Liebigs Ann. Chem., 1980, 28.
334
J. H. Hones and M. J. Witty, J. Chem. SOC., Perkin Trans. 1, 1979, 3203.
335
M. Pinza, G. Pifferi, and F. Nasi, Synthesis, 1980,SS.
336
J. Drapier, A. Feron, R. Warin, A. J. Hubert, and P. Teyssie, Tetrahedron Lett., 1979, 559.
337
M. Regitz, B. Weber, and A . Heydt, Liebigs Ann. Chem., 1980, 305.
(-)-Ephedrine and tosylallene combine to form the oxazolidine (526) in a
stereospecific addition.”’ The action of ketens R2R3C=C=0 on the fluoren-
ylidenenitrones (527) may result in spiro-oxazolidinones (528) or the spiro-
isoxazolidinones (529), depending on the nature of the groups R’to R3.”’
R
0X Y O C H ,Ph
%0
’R
(527)
Reactions of Oxazoles. The reaction of 4-phenyloxazole with di(acetoxy-

methy1)acetylene gives the furan (531; R = CH20Ac) by extrusion of benzo-
nitrile from the intermediate Diels-Alder adduct (530; R = CH,OAC).~~’
Similarly, 5 -cyano-4-methyloxazole and hept- 1-yne yield mainly the furan (532)
and methyl cyanide; a minor product, the 4-substituted isomer (533), arises from
the alternative mode of addition of the acetylene.341 The sensitized photo-
oxidation of 2,4-diphenyl-2-oxazolin-5-one (534)affords, inter alia, the coupled
product ( 535).342
(533) 4-substituted
The meso-ionic oxazolium 5-oxide (536; R = Ph) reacts with methyl-p-
benzoquinone to yield the isoindole-4,7-dione (537).’43 The monophenyl-
compound (536; R = H ) is transformed photochemically into the valence-isomer
(538), which has been intercepted as the ester PhCONMeCH2C02Et by its
reaction with N-Benzoyl-N-benzylamino-a-phenylacetonitrile (539)
may be regarded as an open-chain analogue of a Reissert compound; it is
transformed into the hydrofluoroborate (540) of the oxazolium 5-imide (541);
33a M. Cinquini, F. Cozzi, and M. Pelosi, J. Chem. Soc., Perkin Trans. 1, 1979, 1430.
339 M. A. Abou-Gharbia and M. M. JoulliC, Heterocycles, 1979, 12, 909; M. A. Abou-Gharbia and
M. M. JoulliC, J. Org. Chem., 1979, 44, 2961.
340 3. Hutton, B. Potts, and P. F. Southern, Synth. Commun., 1979, 9, 789.
341 T. Jaworski, T. Mizerski, and A. Krokilowska, Pol. J. Chem., 1979, 53, 1799.
342 V. M. Dixit, V. Bhat, A. M. Trozzolo, and M. V. George, J. Org Chem., 1979, 44, 4169.
343 J . A. Myers, L. D. Moore, Jr., W. L. Whitter, S . L. Council, R. M. Waldo, J. L. Lanier, and B. U.
Omoji, J. Org. Chem., 1980,45, 1202.
344 N. H. Toubro, R . Hansen, N. Harrit, A. Holm, and K . T. Potts, Tetrahedron, 1979, 35, 229.
\
C-NMe
// \
(543)
E = C02Me
this, on treatment with dimethyl acetylenedicarboxylate, yields the pyrrole (543)
via the dipolar cyclo-adduct (542).34sIrradiation of the azlactone (544) in the
solid state leads to the dimer (545);346the reaction has been extended to other
oxazolinone~.~~’
Benzoxazo1es.-Benzoxazole is cleaved by thiophosgene to the isocyanate
(546).”* The chlorobenzoxazolium salt (547) transforms cyanhydrins
RCH(0H)CN into the corresponding chloro-compounds RCHC1CN349and it
dehydrates ketones RCH2COAr to the acetylenes R C Z C A ~ . ~ ~ ”
(544) (545)
Other Systems.-The kinetics of the acid-induced cyclization of the allenes (548)
to the oxaphospholium ions (549) have been determined.351The stable crystalline
bromo-oxaiodole (550) is recommended as a useful reagent for allylic and
benzylic b r ~ m i n a t i o n . ~ ’ ~
345 W . E. McEwen, A. V. Grossi, R . J. MacDonald, and A . P. Stamegna, J. Org. Chem., 1980,45,1301.
346 S. Mohr, Tetrahedron Lett., 1979, 2461.
347 S. Mohr, Tetrahedron Lett., 1979, 3139.
348 A . W. Faull and R. Hull, J. Chem. Res. ( S ) , 1979, 148.
349 T. Mukaiyama, K. Kawata, A . Sasaki, and M. Asami, Chem. Left., 1979, 1 1 17.
350 T. Tsuji, Y. Watanabe, and T. Mukaiyama, Chem. Lett., 1979, 481.
351 T. S. Mikhailova, E. D. Chunin, N. K. Skvortsov, V. M. Ignatev, and B. I. Ionin, Zh. Obshch. Khim.,
1979,49, 1752.
3s2 R. L. Amey and J. C. Martin, J. Org. Chem., 1979, 44, 1779.
6 Systems containing Three Identical Heteroatoms

1,2,3-Triazoles and Benzotriazo1es.-Formation. Treatment of the phosphorane
EtOC(S)CH=PPh, with tosyl azide yields the betaine ( 5 5 l).353 The triazole (552)
is formed by the reaction of diazomethane with the chlorinated imine
C13C-CC1=NCH2C1.354 2,2,2-Trifluorodiazoethane,F3CCHN2,combines with
hexafluoroacetone imine to give a mixture of the rearranged imine (553) and the
triazoline (554).i 4 5 Bis(acy1hydrazones) ( 5 5 5 ) of methylglyoxal are dehydro-
genated by lead tetra-acetate to yield mixtures of isomeric triazolyl-isoimides
(556; R’ = H, R2 = Me) and (556; R’ = Me, R2 = H);356similar treatment of
o-arylazo-anilines (557) affords benzotriazoles (558).”’
R
ArCONHN=CHCMe=NNHCOAr
(555)
I
OCOAr
Y
Ar
(556)
Reactions of 1,2,3-Triazoles and Benzotriazoles. The 13Cn.m.r. spectrum of a
solution of C-vinyl-1,2,3-triazole in DMF, at -55 “ C ,shows the presence of three
equilibrating tautomers, in which the proton is attached t o any one of the nitrogen
atoms.358l-Chloro-4,5-diphenyl-1,2,3-triazole (560), obtained by the action of
sodium hypochlorite on the triazole (559), decomposes on heating or after
standing for a long time to the (diphenylaziriny1)triazoIe (563), by way of the
4H-triazole (561) and the chloro-azirine (562).359Aryl azides ArN3 (Ar = p-
CIC6H4, p-02NC6H4, or p-NCC6H,) add to 1,2-dipiperidinoethene to yield
353 H. J. Bestmann and W. Schaper, Tetrahedron Lett., 1979, 243.
354 H. Bohme and H. J. Drechsler, Chem.-Ztg., 1979, 103, 188.
3ss R. Fields and J. P. Tomlinson, J. Fluorine Chem., 1979, 14, 19.
356 N. A. Rodios and N. E. Alexandrou, J. Heterocycl. Chem., 1979, 16, 571; J. Stephanidou-
Stephanatou, E. Varella, E. D. Micromastoras, and N. E . Alexandrou, ibid., P I 1373.
357 L. K. Dyall, Aust. J. Chem., 1979, 32,643.
358 S. Toppet, S. Wouters, and G. Smets, Org. Magn. Reson., 1978, 11, 578.
359 T . C. Gallagher, M. J. Sasse, and R. C. Storr, J. Chem. Soc., Chem. Commun., 1979, 419.
unstable triazolines (564) which decompose spontaneously to the imines (565).36"
Heating the methoxy-triazoline (566) affords a mixture of the triazole (567) and
the imine (568).361A new type of 2-azabutadiene, i.e. (570), has been prepared by
pyrolysis of the triazoline (569). The diene readily undergoes Diels-Alder
reactions with electron-poor alkynes; methyl propiolate, for example, affords the
pyridine ester (57 1) with elimination of p y r r ~ l i d i n e Whereas
. ~ ~ ~ the N-phenyl-
triazoline (572; R = Ph) affords the aziridine (573) on heating, the N-methyl-
Ph
PhCFN
N
R
Ph zyN
analogue (572; R = Me) yields the pyrrolidine (574).363
c1 N c1
Ph
(559)
(559) R = H (561)
(560) R = C1 (563)
(570) (572) E = C02Me

NR2 = pyrrolidino
EffE Q
NC f ; c : , h
NC N E
' N
R
' kPh
Me (575) (576)
(573) (574)
E = COzMe
E.s.r. spectroscopy of the biradical (576), generated by photolysis of 1-
phenylbenzotriazole (575; R = Ph), shows that it exists in two
Irradiation of a solution of benzotriazole (575; R = H) in benzene produces a
mixture of 2-aminobiphenyl and 1-anilinobenzotriazole (575 ;R = PhNH),365.366
while o-aminophenol is obtained in the presence of dilute sulphuric
360 L. Citerio, M. L. Saccarello, and P. Trimarco, J. Heterocycl. Chem., 1979,16, 289.
361 G. A. Lanovaya and V. F. Mishchenko, Zh. Org. Khim., 1979,15,2203.
362 Y. Nomura, Y. Takeuchi, S. Tomoda, and M. M. Ito, Chem. Lett., 1979, 187.
363 M. S. Ouali, M. Vaultier, and R. CarriC, Bull. SOC.Chim. Fr., Part2, 1979, 633.
364 H. Murai, M. Torres, and 0. P. Strausz, J. A m . Chem. SOC.,1980,102, 1421.
365 F. Razrnara, B. Behjati, N. Aftandilians, and T. Bluhm, J. Heterocycf.Chem., 1979,16, 1641.
366 M. Marky, H. Schmid, and H. J. Hansen, Helu. Chim. Acta, 1979,62, 2129.
196 He te r o c y c lic Che m ist r y
1,2,4-Triazoles.-Formaldehyde N’-methyl-N’-tosylhydrazone, H2C=N-
NMeTos, reacts with ammonia to give l-methyl-1,2,4-triazole (577).”’
Cycloaddition of thionitrosodimethylamine, Me2N-N=S, to the tetrazine ester
(578) yields the triazole (579) with extrusion of nitrogen and The
formaticy of the triazolinones ( 5 8 0 ) from N-phenylbenzonitrile imine
(PhCEN-NPh) and aroyl azides involves a Curtius rearrangement of the latter
to aryl i s o c y a n a t e ~ . ~ ~ ~
(577) R’ = Me, R2 = H (578)

(581) R’ = NO2, R2 = NH2
(582) R’ = H, R2 = N H N 0 2
5-Amino-l-nitro-l,2,4-triazole (581), obtained by nitration of 5-amino-
triazole with acetyl nitrate, rearranges, on heating, to the nitramino-triazole
(582).370The combined action of sodium hydroxide, potassium iodide, tri-
ethylamine, and sodium dihydrogen phosphite on the chloro-nitro-triazole (583)
results in a mixture of the rearranged triazole (584), 3-chloro-l,2,4-triazole,
and
the coupled product (585).371The stable betaine (586) has been prepared by
treatment of 4-phenyl- 172,4-triazolewith phenacyl hromide, followed by tri-
~ ~ ~meso-ionic triazolium thiolate (537; X = S) reacts with
e t h ~ l a m i n e .The
chlorine to form the dichloride (587; X = SC12), which has been converted into
the betaine (588) by the action of diethyl bromomalonate in the presence of
triethylamine.373
R
PhNs-‘
(-jN
N N N N
R’ H I Me
(585) CHCOPh
583) R’ = NOz, R2 = . H (587) R = X- -
584) R’ = H, R2 = NO2 (588) R = S-C(CO,Et),
4-Phenyl-l,2,4-triazoline-3,5-dione (589) reacts with primary alcohols ROH
to yield the ester-amides (590) and nitrogen, while tertiary amines or pyridine
afford the bicyclic compound (591).”‘ With heptalene, a mixture of
stereoisomeric cyclo-adducts (592) is Thermolysis of the amino-
azimine (593) yields mainly phenyl isocyanate and dimethylcarbamoyl azide,
Me2NCON3.376
367 N. N. Makhova, N. V. Trifonova, L. I. Khmelnitskii, and S. S. Novikov, Izv. Akad. Nuuk SSSR,
Ser. Khim., 1979, 1636.
368 G . Seitz and W. Overheu, Chem.-Ztg., 1979, 105, 230.
369 A. F. M. Fahmy, A. Hamed, H . Baddawy, and H. Abdel Fadel, Indian J. Chem., Sect. B, 1979,18,
369.
370 M. S. Pevzner, T. N. Kulibabina, N. A. Povarova, and L. V. Kilina, Khim. Geterotsikl. Soedin.,
1979, 1132.
371 M . S . Pevzner, T. N. Kulibabina, and L. A. Malinina, Khim. Geterotsikl. Soedin., 1979, 5 5 5 .
372 M. Petrovanu, C. Luchian, G. Surpateanu, and V. Barboiu, Rev. Roum. Chim., 1979, 24, 733.
373 A. Ya. Lazaris, A. I. Kalinin, and A. N. Egorochkin, Izv. A k a d . NaukSSSR,Ser. Khim., 1979,2717.
374 H. Dao Le and D. Mackay, Can. J. Chem., 1979,57,2727.
37s L. A. Paquette, A. R. Browne, and E. Chamot, Angew Chem., Int. Ed. Engl., 1979, 18, 546.
376 E. Fahr, M. J. Richter, and N. Pelz, Tetrahedron Lett., 1979, 1741.
0
PhN-f 0 PhNyo
AN
O
4N A
N'
NCONHPh PhN I
C02R 0 0
(589)
(590) (591)
I
Ph NMe,
(592) (593)
7 Other Systems containing Three Heteroatoms

Oxadiazoles.-1,2,3-Oa~iazu~e~. 3-Phenylsydnone (594;R = H) is anodically
chlorinated at position 4,377while anodic oxidation yields mainly phenol and
b e n ~ a l d e h y d e The
. ~ ~ ~foregoing sydnone reacts with tetracyanoethylene to give
the ene-hydrazone (596), presumably via the cyclo-adduct ( 5 9 9 , by loss of
carbon dioxide and cleavage of the strained carbon-carbon single bond.379
Irradiation of diphenylsydnone (594; R = Ph) in the presence of, methyl pro-
piolate affords the pyrazole (597)by way of the nitrile imine PhCEN-NPh; with
benzonitrile, a mixture of the 1,2,3- and 1,2,4-triazoles (598)and (599), together
with the 1,3,4-oxadiazolinone (600) and N-benzoyl-N'-phenylhydrazine,is
formed.380NN'-Dibenzoylphenylhydrazineis produced by photo-oxygenation
of diphen ylsydnone. 381
Photoelectron spectroscopy indicates that, in the gas phase, the diazocyclo-
hexadienone (601) exists in equilibrium with the valence isomer (602).382
Q H
377 H.-J. Tien, T . Nonaka, and T. Sekine, Chem. Lett., 1979, 283.
378 H.-J. Tien, T. Nonaka, T. Fuchigami, and T. Sekine, Denki Kuguku oyobi Kogyo Butsuri Kagaku,
1979,47,449 (Chem. Abstr., 1980,92, 5828).
379 H. C. Berk and J. E. Franz, J. Org. Chem., 1979,44,2395.
380 H. Gotthardt and F. Reiter, Chem. Ber., 1979, 112, 1206, 1635.
381 V. Bhat, V. M. Dixit, B. G. Ugarker, A. M. Trozzolo, and M. V. George, J. Org. Chem., 1979, 44,
2957.
382 R. Schulz and A. Schweig, Angew. Chem., Int. Ed. Engl., 1979,18, 692.
1,2,4-O.undiazoles. N-Aroyl-N'N'-dimethylformamidines, ArCON=CHNMe2
[which are prepared by condensing dimethylformamide dimethyl acetal,
Me2NCH(OMej2, with amides ArCONH2], are converted into 5-aryl- 1,2,4-
oxadiazoles (603) by the action of h y d r ~ x y l a m i n e The
. ~ ~ ~3-benzyl-5-methyl-
derivative (604) is formed when N-acetyl-N-nitrosopheinylalanineis irradiated
in the presence of triethylamine."' Nitrones R'CH=N(Bu')-O add isothio-
cyanates R2NCS to form the thiones (605;R', R2 = alkyl or a r ~ l ) . ~ "
H H
(603) R' = Ar, R2 = H (605)

H
(606) (607)
(604) R' = Me, R2 = CH2Ph
3-(2-Aminoethyl)-1,2,4-oxadiazoles (606; R = alkyl or aryl) readily isomerize
to 3-acylamino-2-pyrazolines (607) on heating.386 Treatment of the salt (608)
with triethylamine yields the transient ylide (609), which decomposes to methyl-
phenylcarbodi-imide (610).387 2,3-Diphenyl-l,2,4-oxadiazolin-5-one(611)
rearranges photochemically to a mixture of the oxadiazolinones (612) and (613);
pyrolysis gives 2-phenylbenzimidazole with extrusion of carbon The
oxadiazole (614) rearranges thermally to the indazole (615).389
H
1,2,5-Oxadiatoles. A new product, the furoxan (616),has been isolated from the
reaction of sorbic acid with sodium nitrite.390 Flash vacuum pyrolysis of the
383 Y.-I. Lin, S. A. Lang, Jr., M. F. Lovell, and N. A. Parkinson, J. Org. Chem., 1979, 44, 4160.
384 J. Polo and Y. L. Chow, Heterocycles, 1978, 11, 101.
38s G . Zinner and E. Eghtessad, Arch. Pharm. (Weinheim, Ger.), 1979, 312,907.
386 D. Korbonits, E. M. Bako, and K. Horvath, J. Chem. Res. ( S ) , 1979.64.
387 R. A. Olofson and K. D. Lotts, Tetrahedron Lett., 1979, 3131.
388 J. H. Boyer and P. S . Ellis, J. Chem. SOC.,Perkin Trans. 1, 1979, 483.
389 N. Vivona, G . Cusmano, G . Macaluso, V. Frenna, and M. Ruccia, J. Heterocycl. Chem., 1979, 16,
783.
39" T. Osawa, Y. Kito, M. Namiki, and K. Tsuji, Tetrahedron Lett., 1979, 4399.
furoxan (617) reversibly yields acetonitrile oxide (618), which was identified by
'H and I3C n.m.r. spectro~copy.~~' The furoxan (619), obtained by the action of
sodium hypochlorite on the dioxime of cyclopentane- 1,2-dione, reacts with
benzonitrile to give the bis-oxadiazole (621), indicating preliminary cleavage to
glutaronitrile dioxide (620).392 Me
+dH=CHC02H Me Me I
+m=2 C(11 +
,N, /N /N\ /N N
-0 0 -0 0 I
/H\+n+
(616) (6 17) -0
(618)
+I \
+ "- N' JPh
Ph< /N
-0
,N\
O
/N -o/ \
0- 0 '0
(621)
(6 19) (620)
Hydrogen transfer from hydrazobenzene to benzofuroxan (622) results in
azobenzene and o-benzoquinone dioxime (623).393Compound (622) reacts with
formaldehyde to yield the benzimidazolinone (624).394 Chlorobenzofuroxan
aldehyde condenses with derivatives of hydroxylamine or hydrazine to yield
oximes or hydrazones (625; R = OH, OMe, NHPh, NMe,, etc.), which rc-
arrange thermally to indazoles (626).395 Treatment of 7-methoxy-4-nitro-
benzofurazan 1-oxide with aqueous potassium hydroxide affords a mixture of
the corresponding 7-hydroxy-compound (627) and the rearranged 5-hydroxy-
4-ni tro benzof uroxan (628).396
&\O
\ &'' \
R'
0-
(622) R' = R2 = H
(625) R' = C1, R2 = CH=NR
(627) R' = OH, R2 = NO2
391 W. R. Mitchell and R. M. Paton, Tetrahedron Lett., 1979, 2443.

392
J. F. Barnes, M. J. Barrow, M. M. Harding, R. M. Paton, P. L. Ashcroft, J. Crosby, and C. J. Joyce, J.
Chem. Res. ( S ) , 1979, 314.
393 M. M. El-Abadelah, Z. H. Khan, and A . A . Anani, Synthesis, 1980, 146.
394 J. Schmidt and G . Zinner, Arch. Pharm. (Weinheim, Ger.), 1979, 312, 1019.
395 A . J. Boulton, K.-W. Thoe, S. N. Balasubrahmanyam, I. M. Mallick, and A . S. Radhakrishna, J. Org.
Chem., 1980,45, 1653.
396 E. Buncel, N. Chuaqui-Offermanns, and A. R. Norris, Can. J. Chem., 1979, 57, 2512.
1,3,4-Oxadiazoles. a -Ethoxybenzaldehyde acylhydrazones, EtOCPh=N-
NHCOR (R = alkyl), which arc formed by the action of benzo-
trichloride on ethanol and acylhydrazines, cyclize thermally to the 1,3,4-0xadi-
azoles (629).3y7 The cyclic azo-compound (630) is produced by the
action of diphenyldiazomethane on di-(p-methoxybenzoyl)diazomethane,
(ArC0)2CN2 (Ar = p-MeOC6H4), the key step being Wolff rearrange-
ment of the latter to the keten ArCOCAr=C=0.398 Photolysis of the
oxadiazolinone (631) yields carbon dioxide and the tetra-azahexatriene
PhN =N -CMe=CMe -N=NPh . 3 y 9 2,3,5 -Triphenyl-1,3,4-0xadiazolium per-
chlorate (632) undergoes cationic [ 4 n + 27r] cycloaddition to 1-(diethyl-
amino)propyne to give (633), which forms the fused cyclobutene (634) on
treatment with dimethyl acetylenedicarbo~ylate.~~~
Ph& 0
(629)
Phosphorus Compounds.-Treatment of the dioxaphospholen (635) with

sulphur yields a mixture of the oxathiole (636) and trans-dibenzoylstilbene,
PhCOCPh=CPhCOPh."' 2-Phenyl-l,3,2-dioxaphospholan (637; R = Ph)
dimerizes in solution to a ten-membered-ring compound, which was isolated as
. ~ ~ ~cyclic thiophosphorous acid (639) exists in
(638) by s u l p h u r i ~ a t i o n The
equilibrium with the betaine (640) in aqueous The spiro-compound
(641), which contains a phosphorus-hydrogen bond, is formed by the action of
(637; R = Cl) on diethyl The phosphazene (642) spontaneously
cyclizes to the spiro-compound (643).40sStable derivatives (645) and (646;
R = Br) of five-co-ordinate phosphorus have been obtained by the action of
bromine on the o-phenylene phosphite (644).40hThe chlorine analogue (646;
R = Cl) reacts with 3,5-dimethylpyrazole to give the corresponding pyrazole
derivative (646; R = 3,5-dimethylpyrazol-l -yl), which reversibly dimerizes to
the zwitterion (647).407
397 M. Golfier and R. Milcent, Synthesis, 1979, 946.
398 L. Capuano, R. Zander, and P. Zenner, Chem. Ber., 1979,112, 3753.
3yy G . Westphal and D . Schlangstedt, Z. Chern., 1979, 19, 217.
400 H. Franke, H. Grasshoff, and G . Scherowsky, Chem. Ber., 1979,112, 3623.
H. Fauduet a n d R. Burgada, NOUU. J. Chim., 1979, 3, 555.
402 J . P. Dutasta, A . Grand, A. C. Guimaraes, and J . B. Robert, Tetrahedron, 1979, 35, 197.
4''3 V. V. Ovchinnikov, V. I. Galkin, R . A. Cherkasov, and A. N. Pudovik, Zh. Obshch. Khim., 1979,49,
1693.
4'14 M. Koenig, A . Munoz, B. Garrigues, and R. Wolf, Phosphorus Sulfur, 1979,6, 435.
405 M . Sanchez, J . F. Brazier, D. Houalla, a n d R. Wolf, Nouo. J. Chim., 1979, 3, 775.
406 J. Glode and H. Gross, Phosphorus Sulfur, 1979,7, 57; Z. Anorg. Allg. Chem., 1979,458, 108.
407 T. von Criegern and A. Schmidpeter, 2. Nuturfnrsch., Ted B, 1979, 34, 762.
(640)
pJ>R
\
(644) R = OC6H40Me-o
(645) R = Br3
R
(646)
The oxide radical (648) exchanges the unpaired electron, as evidenced by e.s.r.
Treatment of the catechol with phosphorus pentachloride yields,
inter alia, the spiro-dioxaphospholan (649), which equilibrates with the six-co-
ordinate phosphorus acid (650).409A hexa-t-butyl-derivative is obtained by the
joint action of white phosphorus and triethylamine on 3,5-di-t-butyl-1,2-benzo-
q~inone.~lO
The oxathiaphospholen derivative (65 1)is produced by the action of (EtO),PCI
~~
on thiocyanatoacetone, MeCOCH,SCN.411 Treatment of 1,4-di(acetyl-
Bu' Ph Bu' Bu' Ph Bu'

(648)
0 OH H+
(649) (650)
408
A. I. Prokofev, T. I. Prokofeva, I. S. Belostotskaya, N. N. Bubnov, S. P. Solodovnikov, and V. V.
Ershov, Dokl. A k a d . Nauk SSSR, 1979,246,340.
409
M. Koenig, A. Klaebe, A. Munoz, and R. Wolf, J. Chem. SOC.,Perkin Trans. 2, 1979, 46.
410
M. I. Kabachnik, D. I. Lobanov, and P. V. Petrovskii, Izu. A k a d . Nauk SSSR, Ser. Khim., 1979,
2398.
41 1
Zh. M. Ivanova, T. V. Kim, I. E. Boldeskul, and Yu. G. Gololobov, Zh. Obshch. Khim., 1979,49,
1464.
amino)butane-2,3-diol with hexaethylphosphoric triamide yields the bis-

oxazaphospholanyl (652).412 o-Aminophenol reacts with diphenyl-
trifluorophosphorane, Ph2PF3, to form the benzoxazaphosphole (653).413The
kinetics of the ring-opening of the spiro-phosphorane (654) and of the ring-
closure of the benzoxazaphosphole (655) have been measured by means of 31P
n.m.r. The X-ray structure of the diazaphosphole (656) has been
reported.415Hexamethylphosphortriamide reacts with monoalkyl-a-phenylene-
diamines to give bi-co-ordinated phosphorus heterocycles (657), which can be
isolated as stable complexes with boron t r i f l u ~ r i d e . ~ ~ ~
Miscellaneous Other Systems containing Three Heteroatoms-Stable

paramagnetic complexes (658) are formed from diarylborinic acids Ar2BOH and
3 -t-butyl-5- m e t h y l ~ a t e c h o l .2,2-Dimethyl-
~~~ 1,3,2-benzodioxastannole (659;
X = 0) and the corresponding benzoxathiastannole (659; X = S) serve as
starting materials for the synthesis of numerous heterocyclic systems; thus
treatment of the former with phenyldichlorostibine yields the benzodioxastibole
(660); chlorine derivatives of phosphorus and arsenic react similarly.418
412 L. I. Mizrakh, L. Yu. Polonskaya, and N. V. Ulanovskaya, Zh. Obshch. Khim., 1979,49, 2393.
413 H. B. Stegmann, H. V. Dumm, and K. Scheffler, Phosphorus Sulfur, 1978,5, 159.
414 B. Garrigues, Bui Cong Chanh, A. Munoz, and A. Klaebe, J. Chem. Res. ( S ) , 1979, 172.
41s J. H. Weinmaier, J. Luber, A. Schmidpeter, and S. Pohl, Angew Chem., Znt. Ed. Engl., 1979,18,412.
416 C. Malavaud, M. T. Boisdon, Y. Charbonnel, and J. Barrans, Tetrahedron Lett., 1979, 447.
417 H. B. Stegmann, G . Denninger, and K. Scheffler, Tetrahedron Left., 1979, 3689.
418 C. Anchisi, A. Maccioni, G. Podda, and M. Secci, Rend. Semin. Fac. Sci. Univ. Cagliari, 1978, 48,
285 (Chem.Abstr., 1979,91,193 232); C. Anchisi, L. Corda, A. Maccioni, G. Podda, and M. Secci, J.
Heterocycl. Chem., 1979, 16, 1439.
8 Systems containing Four Heteroatoms
Tetrazo1es.-a-Azido-oximes, R’C(N,)=NOH, cyclize to 1-(acyloxy)tetrazoles
(661) when treated with acid chlorides RCOC1.419The action of hydrazoic acid on
unsymmetrical carbodi-imides PhN=C=NR (R = alkyl) leads to 1-phenyl-5-
(alky1amino)tetrazoles (662); at 200 “C,these undergo a Dimroth rearrangement
to yield the 1-alkyl-5-anilino-isomers (663).420
(Diphenylmethy1)tetrazoles(664)
are produced in the reaction of N-aryl-diphenylketeniminesPh2C=C=NAr with
hydrazoic Diethoxy disulphide, (EtO),S2, dehydrogenates NN’-dianil-
inothiourea to dehydrodithizone (665).422‘Diformazyl’ has been shown to be the
betaine (666).423
(661) R2 =
(662) R’ = NHR, R2 = Ph (666)
(663) R’ = NHPh, R2 = R
(664) R’ = CHPh2, R2 = Ar
N=N
(668) Fu = 2-fury1 (669)
(671)
Flash vacuum pyrolysis of 5-(2-furyl)-2-phenyltetrazole (667) at ca. 400 “C
yields the indazole (670),whereas at higher temperatures the benzofulvene (67 1)
is obtained. The authors have suggested that (668) and (669) are key inter-
mediates in these Another intriguing process is the formation of
2-phenylbenzotriazole (675) when the tetrazole (672) is thermolysed; the pro-
posed mechanism (see Scheme 8) receives support from the isolation of the
benzotriazinone oxide (673b) and the spectroscopic detection of the isocyanate
(674).425
419 J. Plenkiewicz, Tetrahedron, 1978, 34, 2961.
420 J. Svetlik, I. Hrusovsky, and A. Martvon, Collect. Czech. Chem. Commun., 1979,44, 2982.
421 J. Svetlik and A. Martvon, Collect. Czech. Chem. Commun., 1979, 44, 2421.
422 H. Kagami and S. Motoki, Bull. Chem. SOC.Jpn., 1979, 52, 3463.
423 F. A. Neugebauer, H. Fischer, and C. Krieger, Chem. Ber., 1979, 112, 2369.
424 C. Wentrup and J. Benedikt, J. Org. Chem., 1980, 45, 1407.
425 P. G. Houghton, D. F. Pipe, and C. W. Rees, J. Chem. SOC., Chem. Commun., 1979, 771.
2 04 Heterocyclic Chemistry
-0
(673a) X = NPh, Y = 0
(673bj X = O , Y = NPh
Scheme 8
Oxatriazoles and a Triazaphospho1e.-The mass spectra of representatives of ten

meso-ionic systems have been analysed; mass spectroscopy is useful for dis-
tinguishing between isomers belonging to different classes, such as the oxatri-
azolium N-phenylimide (676) and its rearrangement product, the tetrazolium
oxide (677).426Compound (676) combines with p-chlorophenyl isocyanate to
form the 1,3-dipolar cyclo-adduct (678; Ar = p-ClC6H4),which loses phenyl
isocyanate to give the oxatriazolium N-p-chlorophenylimide (679).427Photolysis
of the oxatriazolium oxide (680) yields mainly carbon dioxide and phenyl azide; a
labelling experiment using "N shows that the azide arises by migration of the
' ~ X-ray analysis of the tri-
phenyl group and not uia a t r i a ~ i r i d i n e . ~The
azaphosphole (681) has been
N,yyPh
A-+jN
-
Me
y x
(676) X = 0 , Y = NPh
r Y MN e
(677) X = N P h , Y = 0
(679) X = 0 , Y = NAr
(680) X = 0, Y = 0
9 Compounds containing Two Fused Five-Membered Rings ( 5 3 )

Hypervalent Sulphur Compounds and their Selenium and Tellurium Analo-
gues.-The reaction of the trithiapentalene (682; R = Me) with trimethylsilyl or
tributylstannyl radicals, which occurs at S-1,has been studied by e.s.r. spec-
~ ' 'H n.m.r. spectra of trithiapentalene (682; R = H) and the
t r o ~ c o p y . ~The
dioxathiapentalene (683), determined for the nematic phase, indicate that both
426 R. N. Hanley, W. D. Ollis, and C. A. Ramsden, J. Chem. Suc., Perkin Trans. 1, 1979, 747.
427 R. N. Hanley, W. D. Ollis, and C. A. Ramsden, J. Chem. Suc., Perkin Trans. 1, 1979, 736.
428 C. Bjerre, C. Christophersen, B. Hansen, N. Harrit, F. M. Nicolaisen, and A. Holm, Tetrahedron,
1979, 35, 409.
429 S. Pohl, Chem. Ber., 1979, 112, 3159.
43" K. U. Ingoid, D. H. Reid, and J. C. Walton, J. Chem. Soc., Chem. Commun., 1979, 371,
have C2v~ y m m e t r y . ~Dioximes
~‘ of 1,3-dicarbonyl compounds (684; R’ = H,
Me, or C02Et; R2 = H or Ph) are converted into 1,6-dioxa-6ah4-thia-2,5-
diazapentalenes (685; X = S) by the action of disulphur dichloride; selenium
dioxide or tellurium dioxide yield the analogues (685; X = Se) and (685;
X = Te).432Thia-, selena-, and tellura-tetra-azapentalenes [686; X = S, Se, or
Te; Ar = 2,4-(N02),C6H3] have been prepared similarly from the bis-2,4-
dinitrophenylhydrazones of compounds (684).433Treatment of the dithiadi-
azapentalene (687) with methylamine produces the thiatriazapentalene (688).434
Several 1 -aza-6a-thiapentalenes with additional heteroatoms have been
synthesized, starting with isothiazole-5 -aldehyde.435Its oxime reacts with methyl
fluorosulphonate to yield the salt (689); this forms the novel oxadiazathiapent-
alene (690) under the influence of aqueous sodium carbonate. Treatment of the
aldehyde with the Wittig reagent MeOCH=PPh3, followed by methylation,
produces the fluorosulphonate (69 1); subsequent addition of methylamine,
sodium hydrogen sulphide, or sodium hydroxide produces the heterothiapent-
alenes (692; X = NMe), (692; X = S), or (692; X = 0),respectively.
0Y’ 2‘N 7
Ph
(q
N’
Me
CH=Z
FSO, qN’
Me
/ y (p NEt
(687) Y = S (689) Z = NOH (690) X = 0, Y = N (693)
(688) Y = NMe (691) Z = CHOMe (692) Y = C H
Nitrogen Systems.-Monoaza-compounds. The sodium salt of pyrrole-2-alde-
hyde reacts with the phosphonoketenimine (EtO),P(O)CMe=C=NEt to yield
the azapentalene (693).436The formation of the pyrrolo-indole (694) from
N-phenylhydroxylamine and the ester OCHCH2CH2C_CCO2Etin the presence
of sodium cyanoborohydride involves a [3,3] sigmatropic r e a ~ r a n g e m e n t . ~ ~ ~
Another member of this class, the quinone (696), is obtained by the acid-
catalysed transannular cyclization of secomitosanequinone (695).438Dimethyl
acetylenedicarboxylate reacts with ethyl 2-chloro-8-styryl-l-aza-azulene-3-
carboxylate (697) to give the adduct (698), which rearranges, on heating, to the
pyrroloaza-azulene (699) ;439 on silica gel, however, compound (700) is formed.440
431 J. P. Jacobsen, J. Hansen, C. T. Pedersen, andT. Pedersen, J. Chem. Soc., Perkin Trans. 2, 1979,
1521.
432 M. Perrier and J. Vialle, Bull. SOC.Chim. Fr., Part 2, 1979, 199.
433 M. Perrier and J. Vialle, Bull. SOC.Chim. Fr., Part 2, 1979, 205.
434 R. M. Christie, D. H. Reid, and R. Wolfe-Murray, J. Chem. SOC.,Perkin Trans. 1, 1979,926.
435 A . G. Briggs, J. Czyzewski, and D. H. Reid, J. Chem. SOC.,Perkin Trans. 1, 1979, 2340.
436 J. Motoyoshiya, J. Enda, Y. Ohshiro, and T. Agawa, J. Chem. SOC.,Chem. Commun., 1979,900.
437 R. M. Coates and C. W. Hutchins, J. Org. Chem., 1979,44,4742.
438 T. Kametani, K. Takahashi, M. Ihara, and K. Fukumoto, Heterocycles, 1979, 12, 933.
439 N. Abe and T. Nishiwaki, J. Chem. SOC., Chem. Commun., 1979,476.
440 N. Abe and T. Nishiwaki, Heterocycles, 1979,12, 1031.
CO,Et
..cl(i:
Me
Me+. Me
(694) O H 0
Q t
CH=CHPh
HC=CHPh
(697)
E = C02Me
(700)
Dehydropyrrolizidine (701) yields the azocenone (702) on methylation followed
by hydrolysis.441Treatment of hexahydropyrrolocarbazole (703) with chloro-
benzene-p-sulphonyl azide in chloroform affords the rearranged trans-fused
compound (704; Ar = p-C1C6H4), whereas the cis-isomer is produced in
dimethyl s u l p h o ~ i d e . ~ ~ ~
(703) (704)
Diata-compounds. The pyrrolo-pyrazole derivative (705) is one of the

products of the action of acids on the tosylhydrazone
H2C=CMe(CH2)2CH=N-NHTos.443 The reaction of 2,5,5-trimethyl-l-pyr-
roline N-oxide (706) with the ketenimine Ph2C=C=NPh yields the pyrrolo-
imidazole (707).444 Pyrazolidin-3-one and 3-chloropropanoyl chloride combine
to form the dioxopyrazolopyrazole (708).445Irradiation of 1-(o-iodoben-
zoy1)imidazole (709 ; R =H) produces the indolobenzimidazolinone (710); the
441 Y. Arata, K. Tanaka, S. Yoshifuji, and S. Kanatomo, Chem. Pharm. Bull., 1979, 27, 981.
442 A . S. Bailey, P. A . BaIdry, and P. W. Scott, J. Chem. SOC.,
Perkin Trans. I, 1979, 2387.
443 R. M. Wilson and J. W. Rekers, J. A m . Chem. SOC., 1979,101,4005.
444 0. Tsuge, H. Watanabe, K. Masuda, and M. M. Yousif, J. Org. Chem., 1979, 44, 4543.
445 D. S. Kemp, M. D. Sidell, and T. J. Shortridge, J. Org. Chem., 1979,44, 4473.
2-methyl-derivative (709; R = Me) undergoes photocyclization at the benzene
ring, yielding (7 1l).446
The pyrrolo-indole (712) forms the tryptophan derivative (713) by the action
of methanolic sulphuric
Me2 Ph2
(705) 0
(706) (707) (708)
(709) (710)
(711)
Ac H
(712) (713)
E = C02Me
Triaza-compounds. Triazolium ylides (714) yield the 1,3-dipolar cyclo-adducts

(715; R = CO,Me or CN) with methyl acrylate or a~rylonitrile.~~' 6-Methyl-
imidazo[l,2-b]pyrazole (716) is methylated at N-5 but acetylated at N-l.449
Tetra- and Hexa-aza-compounds. Electrochemical reduction of dicyanogen
gives the tetra-azapentalene anion (717).450Glyoxal condenses with methylurea
to yield a mixture of isomeric dimethyl-hexahydroimidazo[4,5-d]imidazole-
2,5-diones (718; R' = H, R2 = Me) and (718; R' = Me, R2 = H);451the
formation of 3a,6a-diphenyl-analoguesfrom benzil and urea or methylurea
has been studied k i n e t i ~ a l l y . ~ 'The
ArCOCH'
N*--*
"
Ph
N +
~
p)
diazopyrazole (719) reacts with
R, Ph
N
c
H
p e
ArCO
(714) (715) (716)
446 T. Nakano and A. Martin, J. Heterocycl. Chem., 1979, 16, 1235.
447 T. Hino, M. Taniguchi, A. Gonsho, and M. Nakagawa, Heterocycles, 1979,12, 1027.
448 M. Petrovanu, C. Luchian, G. Surpateanu, and V. Barboiu, Rev. Roum. Chim., 1979, 24, 1053.
449 L. Knutsson and J. Elguero, A n . Quim., 1978,74, 795 (Chem. Abstr., 1979,91,56 912).
450 G. Cauquis and D. Serve, Bull. SOC.Chim. Fr., Part 2, 1979, 145.
451 S. Gautam, R. Ketcham, and J. Nematollahi, Synth. Commun., 1979,9, 863.
452 A. R. Butler and E. Leitch, J. Chem. SOC.,Perkin Trans. 2, 1980, 103.
diphenyldiazomethane, with extrusion of nitrogen, to give the bicyclic azo-

compound (720); 3-diazoindazole similarly affords the benzologue (721).4s' The
triazolotriazole derivative (722) results from the action of phenyl isocyanate on
benzaldehyde azine, PhCH=N-N=CHPh.4s4
A mixture of methyl-derivatives, i.e. (724) and (725), of the novel 1,2,4-
triazolo[2,3-d]tetrazole system has been obtained by methylation of the azido-
triazole anion (723).455
Mixed Oxygen-Nitrogen Systems.-A number of furo[3,2-b]pyrroles (727) have
been prepared by thermolysis of the azidofurylacrylic esters (726).456Tryp-
tophol (728) reacts with iodine azide to yield the furoindole (729);4s7an
*o N
Me
(730)
(727) H
(729)
453 G. Ege and K. Gilbert, Tetrahedron Lett., 1979, 1567.
454 S. Satsumabayashi, H. Nakanb, and S. Motoki, Nippon Shika Duigaku Kiyo, Zppan Kyoiku-kei,
1979,8, 87 (Chem. Abstr., 1979,91, 140 490j.
455 R. N. Butler, T. McEvoy, E. Alcalde, R. M. Claramunt, and J. Elguero, J. Chem. Soc., Perkin Trans.
1, 1979, 2886.
4s6 S. Ferik, Zb. Stud. Ved. Odb. Pr. (Slov. Vys. Sk. Tech. Bratislave, Chemickotechnol. Fak.), 1979, 13
(Chem. Abstr., 1980, 92, 163 873); A. Krutosikova, J. Kovac, and J. Kristofcak, Collect. Czech.
Chem. Commun., 1979,44, 1799.
4s7 M. Ikeda, K. Ohno, M. Katsura, M.-W. Chun, and Y. Tamura, J. Chem. SOC.,Perkin Trans. 1, 1979,
3061.
0x0-derivative (730) of this ring system is formed by Fischer indolization of the

N‘-methyl-N’-phenylhydrazoneof the aldehyde OCHCHMeCH,C0,Et.458 2-
Methylfuran and C-benzoyl-N-phenylnitrone,PhCOCH=N(Ph)-0, combine
to form a mixture of the cyclo-adducts (731) and (732), together with the
condensation product (733).459The N-acyl-nitrone (734; Ad = 1-adamantyl),
generated by oxidation of N-adamantane-1-carbonyl-N-methylhydroxylamine
with silver sulphate, has been trapped as the 1,3-dipolar cyclo-adduct (735) with
COPh
N-phenylmaleimide.460 The complex nitrile oxide (736), prepared from

dichloroglyoxime (HON=CCl-CCl=NOH) and dipropargylamine, forms the
intramolecular cyclo-adduct (737).4613,6-Diphenylpyridazine 1,2-dioxide (738)
rearranges photochemically to the isoxazolo-isoxazole (739), which is also
produced by the oxidation of the dioxime HON=CPhCH=CHCPh=NOH.462
Regiospecific cycloaddition of benzonitrile oxide to the pyrazoline (740) affords
the pyrazolo-oxadiazole (741).463
458 P. Rosenmund and E. Sadri, Liebigs A n n . Chem., 1979,927.

459 L. Fisera, J. Kovac, and J. Poliacikova, Heterocycles, 1979, 12, 1005.
460 S. A . Hussain, A. H. Sharma, M. J. Perkins, and D. Griller, J. Chem. SOC.,Chem. Commun., 1979,
289.
461 A. V. Eremeev, V. G. Andrianov, and I. P. Piskunova, Khim. Geterotsikl. Soedin., 1979, 991.
462 A . Ohsawa, H. Arai, H. Igeta, T. Akirnoto, A . Tsuji, and Y. Iitaka, Tetrahedron, 1979,35,1267; J.
Org. Chem., 1979,44, 3524.
463 J. P. Gibert, C. Petrus, and F. Petrus, J. Heterocycl. Chem., 1979, 16, 311.
A Phosphorus System.-Photoelectron spectroscopy of the bicyclic phosphorane

(742) reveals that it exists in the open form (743) in the vapour the
related radical (744), on the other hand, is stabilized with respect to the rnono-
cyclic valence
c:3 &
Me
0; <o
H
0’ ,‘O
Me
Co-/p.-o
?
Ph
(742) (743) (744)
10 Compounds containing Fused Five- and Six-Membered

Rings (5,6)
Nitrogen Systems.-Munoaza-compounds. Treatment of the azapentalene anion
(745) with dichloromethane and butyl-lithium yields a mixture of indolizine (746;
R = H) and compound (747); it has been established that the latter is not a
precursor of i n d ~ l i z i n e3-Diethylaminoindolizine
.~~~ (746; R = NEt,) is formed
by the reaction of 2-bromopyridine with propargyl alcohol and diethylamine in
the presence of bis(triphenylphosphine)palladium(II) dichloride and copper(1)
iodide.467The pyridinium ylide (748) undergoes 1,5-dipolar cyclization to the
trans-dihydroindolizine (749).468As in previous years, there have been several
reports on the synthesis of the indolizine ring system from pyridinium ylides: the
methide (750; R’ = H, R2 = Ph) adds benzylideneacetophenone to form the
tetrahydroindolizine (751),469 the action of phenyl vinyl sulphoxide,
rJ$ COMe
(752)
464 D . Houalla, M. Sanchez, D . Gonbeau, and G. Pfister-Guillouzo, Nouu. J. Chim., 1979,3, 507.
465 J. H. H. Hamerlinck, P. Schipper, and H. M. Buck, J. Chem. SOC.,Chem. Commun., 1979, 350.
466 U. Burger and F. Dreier, Helv. Chim. Acta, 1979, 62, 540.
467 A . Ohsawa, Y. Abe, and H. Igeta, Chem. Lett., 197.9, 241.
468 L. Hiltunen, T. Pakkanen, T. Pakkanen, and E. Pohjala, Cryst. Struct. Commun., 1979,8, 547.
469 J. Curtze, R. Dach, K . H. Duchardt, and F. Krohnke, Chem. Ber., 1979,112,2197.
PhSOCH=CH2, on the dicyano-derivative (750; R' = R2 = CN) yields 3-

cyanoindolizine (746; R = CN) by a cycloaddition-extrusion process,47othe ylide
(750; R' = H, R2 = C02Et) reacts with 2-furyl-(5-nitro-2-furyl)acetyleneto
give, unexpectedly, the indolizine (752; R = CH2C02Et), together with the
normal product (752; R = H),471and treatment of 4-cyanopyridinium di-
cyanomethide with 1,2,3-triphenylcyclopropene affords 7-cyano-1,2,3-tri-
phenylindolizine (754) by elimination of malononitrile from the primary adduct
9
(753).472
Ph Ph
m@% \ N
K@ / Ph \ N,-/ R
\ N
Ph
NC
CN
(754)
c\ CO,Et
(753) (755)
In the benzo[g]indolizine series, the ester (756) has been obtained from the
isoquinolium ylide (755; R = C02Et) and cyclopentanone (which is a synthetic
equivalent of c y ~ l o p e n t y n e )acetic
, ~ ~ ~anhydride reacts with the ylide to afford the
acetoxy-derivative (757),474and the action of keten on the cyano-analogue (755;
R = CN) leads to the ketone (758).475Diphenylcyclopropenone combines with
1 -methyl-3,4-dihydroisoquinolineto form the rearranged adduct (759).476The
benzo[e]indolizine (761) is one of the products of the thermolysis of the azide
(760)."" Heating indoline with acrylic acid in polyphosphoric acid gives a mixture
of the tri- and tetra-cyclic compounds (762) and (763).478
470 K. Matsumoto, T. Uchida, and L. A. Paquette, Synthesis, 1979, 746.

471 A. Tanaka and T. Usui, J. Heterocycl. Chem., 1979,16, 1409.
472 K. Matsumoto and K. Uchida, Heterocycles, 1979, 12, 661.
473 T. Kato, T. Chiba, and T. Sasaki, Yukuguku Zusshi, 1979, 99, 1051.
474 T. Kato, T. Chiba, and T. Sasaki, Heterocycles, 1979, 12, 925.
475 T. Kato, T. Chiba, S. Tanaka, and T. Sasaki, Heterocycles, 1978, 11, 227.
476 T. Eicher and D. Krause, Tetrahedron Lett., 1979, 1213.
477 K. Yakushijin, T. Tsuruta, and H. Furukawa, Heterocycles, 1979,12, 1021.
478 V. Shankarnarayan and J. R. Merchant, J. Heterocycl. Chem., 1979, 16, 949.
A kinetic study of the nitrosation, at C-3, of the indolizine (764) and of its
nitration, which occurs at C-4', has been presented.479The reaction of diethyl
azodicarboxylate with 2-methylindolizine yields a mixture of the mono-adduct
(765; R = H) and the di-adduct [765; R = N(C02Et)NHC02Et].480 The novel
zwitterion (767; Ar = p-ClC,H,) is formed by the action of chlorobenzene-p-
sulphonyl azide on the cyclohexenoindolizine -(766).481A stable carbo-
selenaldehyde (768) has been obtained by treatment of 2,7-dimethylindolizine
with the dimethylformamide-phosphorus oxychloride complex followed by
sodium hydrogen ~ e l e n i d e . ~ ~ ~
N-NHC0,Et
I
C0,Et
%
(765)
" * w M e
ArS0,N /C=Se
H
(767)
(768)
Diaza-compounds. Phenacyl bromide reacts with 2-aminopyridine 1-oxide to
yield 2-phenylimidazo[ 1,2-u]pyridin-3-01 (769);483another derivative of this ring
system, compound (771), is produced by the action of diphenylketen on the
sulphilimide (770), dimethyl sulphide being eliminated.484(6-Methyl-2-pyri-
dy1)acetyl azide (772) forms the dihydroimidazo[3,4-a]pyridinone (773) on
heating.48s Whereas 1-methylpyrrole-2-aldehyde and other heterocyclic alde-
hydes react with tosylmethyl isocyanide to give oxazoles, e.g. (774), pyrrole-2-
aldehyde affords the 6-azaindolizine (775).486The action of potassium amide on
the derivative (776) of 3-bromopyridine furnishes the pyrrolo[3,4-~]pyridine
(777) by cyclization of an intermediate ~ y r i d y n e . ~ ~ ~
p,=,=php.50
\ N
pN
\
++
N \ N
OH Ph
Ph
(769)
(770) (77 1)
479 L. Greci and J . H. Ridd, J. Chem. Soc., Perkin Trans. 2, 1979, 317.
'13' M. Masumura and Y. Yamashita, Heterocycles, 1979, 12, 787.
'13' T. S. Cameron, R. E. Cordes, A. Terzis, A. S. Bailey, and P. W. Scott, Can. J. Chem., 1979,57,558.
D. H. Reid, R. G. Webster, and S. McKenzie, J. Chem. SOC., Perkin Trans. 1, 1979, 2334.
483 L. W. Deady and M. S. Stanborough, J. Heterocycl. Chem., 1979,16, 187.
'I3' M. Sakamoto, K. Miyazawa, K. Kuwabara, and Y. Tomimatsu, Chem. Pharm. Bull., 1979,27,2116.
M. Iwao and T. Kuraishi, J. Heterocycl. Chem., 1979, 16, 689.
486 H. Saikachi, T. Kitagawa, H. Sasaki, and A. M. Van Leusen, Chem. Pharm. Bull., 1979, 27, 793.
487 I. Ahmed, G. W. H. Cheeseman, and B. Jaques, Tetrahedron, 1979,35, 1145.
Treatment of N-2,4-dinitrophenylpyridinium chloride (778) with phenyl-

hydrazine in acetic acid causes reductive cyclization to yield the pyrido[l,2-
alimidazole (779).4883-Aminocrotononitrile, MeC(NH2)=CHCN, condenses
with quinoline 1-oxide and isoquinoline 2-oxide to form the tricyclic compounds
(780) and (781),re~pectively.~'~ The imidazo[5,1-a]isoquinolinederivative (783)
is obtained by the action of phenyl isothiocyanate on the sodium salt of the
Reissert compound (782).490Triethyl phosphite reduces the o-nitrophenyldipyr-
rolylmethane (784; R = N 0 2 ) to the nitrene (784; R = N), which forms the
pyrrolo[3,2-b]quinoline derivative (785) by an intramolecular insertion reac-
t i ~ n3-Amino-1H-isoindole
. ~ ~ ~ (786) reacts with acetylacetone in the presence of
perchloric acid to yield the pyrimidoisoindolium salt (787).492
~A+-02 (--fao2
+e
1 / + 1 /
6 3 MCN e
/
C1- (779)
(778) (780)
&N B C N
\ N >e '\ NC0,Me

CN \ N<
0
(781) (782) (783)
488 K. Ostherheld, B. Prajsnar, and H. J. Hauser, Chem.-Zrg., 1979, 103, 190.

489 H. Yarnanaka, H. Egawa, and T. Sakamoto, Chem. Pharm. Bull., 1979,27, 1004.
490 B. C. Uff, R. S. Budhram, and V. Harutunian, Chem. Znd. (London), 1979, 386.
491 G . Jones and W. H. McKinley, J. Chem. SOC., Perkin Trans. 1, 1979, 599.
492 A. K. Tyltin, V. A. Kovtunenko, and F. S. Babichev, Khim. Geterotsikl. Soedin., 1979, 990.
214 He terocy c Eic Chemistry
3-Bromo-l-nitroimidazo[1,5-a]pyridine (789) results when the salt (788) is

treated with nitric
Triaza-compounds. 1,l , l ,-Trifluoroacetylacetone condenses with cyano-
acetylhydrazine to give a mixture of the pyridone (790) and the pyrazolopyridine
(791).494Thermolysis of the azide (792) leads to the rearranged pyrrolopyridaz-
inone derivative (793).495The complex heterocycle (796) is the unexpected
product of the reaction of 4,5 -diaminopyrimidine (794) with benzo.-
cyclobutanedione (795).496
0 0
(794) (795)
m-Chloroperbenzoic acid cleaves the imidazole ring of the N-oxide (797),

forming the pyridazine (798).497 2 -t -B ut ylpyrrolo[ 3,4 -b lquinoxaline (799), pre -
pared from the 1,3-dihydro-c0mpound by dehydrogenation with manganese
dioxide, gives the Diels-Alder product (800) with dimethyl acetylene-
dicarboxylate; dimethyl azodicarboxylate, on the other hand, affords a mix-
ture of the mono-adduct (801) and the analogous 1 , 3 - d i - a d d ~ c t . ~The ~*
imidazopyridine (802) is converted into the triazolopyridine (803) by tht:
combined action of nitric and nitrous acids; the authors suggest that the reaction
proceeds by hydration of the imidazole ring, cleavage to a N-nitroso-compound,
and re-cyclization, with elimination of formic acid.499
Tetra-ata-compounds. The isoindolotetrazine (804), prepared from phthalic
anhydride and NN'-diaminoacetamidine, H2NNHCMe=NNH2, undergoes
493 E. E. Glover, L. W. Peck, and D. G . Doughty, J. Chem. Soc., Perkin Trans. 1, 1979, 1833.
494 R. Balicki and P. Nantka-Namirski, Pol. J. Chem., 1979, 53, 1515.
495 I. Maeba and R . N . Castle, J. Heterocycl. Chem., 1979, 16, 1213.
496 J. W. Barton, M. C. Goodland, K. J. Gould, J. F. W. McOmie, W. R. Mound, and S. A. Saleh,
Tetrahedron, 1 9 7 9 , 3 5 2 4 1 .
497 K. Satoh and T. Miyasaka, Heterocycles, 1978, 10, 269.
498 R. Kreher and G . Use, Tetrahedron Lett., 1978, 4671.
499 Yu. M. Yutilov, A. G. Ignatenko, and 0. G. Eilazyan, Khim. Geterotsikl. Soedin., 1980, 121.
Five-Membered Ring Systems 215
N>>x
\
(802) X = CH
(803) X = N
methanolysis to yield the tetrazine (805).500 Condensation of hydrazine-NN'-

dicarboxamidine, HN=C(NH2)NHNHC(NH2)=NH, with benzoylacetone
affords the triazolopyrimidine (806).501The coupling product (807) of diazotized
5-amino-3-methylpyrazolewith resorcinol cyclizes in boiling acetic acid to the
pyrazolo[3,2-c][1,2,4]benzotriazine (808); other phenols, as well as diazotized
3-aminoindazole, have been employed in this general 2-Acetyl-7-
methoxytropone and hydrazine yield the diaza-azulene derivative (809), which is
converted into the tricyclic compound (810) on treatment with acetone.503
OH OH
(807) (808) (809) (810)
Penta- and Hem-ma-compounds. 3,6-Dibenzyl-1,2,4,5-tetrazine (811 ) under-
goes a complex reaction with methanolic potassium hydroxide, giving 3-benzyl-7-
methoxy-6-phenylimidazo[ 172-b][1,2,4,5]tetrazine (812), whose structure has
been elucidated by X-ray analysis.5o4Carbon- 13 n.m.r. spectroscopy has been
used to investigate azido-tetrazole valence tautomerism for the systems (813) and
(814)505 *
and for (815) (816) (817).506 +
H. J. Degen, S. Haller, K. Heeg, and H. Neunhoffer, Chem. Ber., 1979,112, 1981.
A. Kreutzberger and G . Risse, Arch. Pharm. (Weinheim, Ger.),1979, 312, 1003.
J. Slouka and J. Kubata, Acta Univ. Palacki. Olomuc., Fac. Rerum Nut., 1978,57 (Chem. 17), p. 173
(Chem. Abstr., 1980,92,215 399); J. Slouka and D. Buczkowska, ibid., p. 179 (Chem. Abstr., 1980,
92,215 400).
A. Yamane, M. Nagayoshi, K. Imafuku, and H. Matsumura, Bull. Chem. SOC.Jpn., 1979,52,1972.
D. G. Neilson, K. M. Watson, and T. J. R. Weakley, J. Chem. SOC.,Perkin Trans. 1 , 1979, 333.
A. Konnecke, E. Kleinpeter, and E. Lippmann, Org. Magn. Reson., 1979,12, 685.
A. Messmer, G. Hajos, J. Tamas, and A. Neszmelyi, J. Org. Chem., 1979, 44, 1823.
Mixed Oxygen-Nitrogen Systems.-Intramolecular cycloaddition reactions have

provided a number of novel compounds. The amino-acid derivative (818) eli-
minates acetic acid on heating, to form the imine (819); this undergoes a
spontaneous Diels-Alder addition to yield a mixture of only two diastereoisomers
(820).'07 The propargyl ether (821) cyclizes thermally to the pyrrolobenzopyran
(823) by way of the 1,3-dipolar tautomer (822).508The rates of formation of the
triazolobenzoxazines (825; R' = H or Me, R2 = H or Ph) from the azides (824)
have been meas~red.'"~The action of triethylamine on the a-chloro-aryl-
methylenehydrazone [826; Ar = 2,4-(N02)&,H3]results in compound (828),
uia the transient nitrile imine (827)."'O The iodine-catalysed conversion of the
aziridine derivative (829) into the oxazoloquinazolinone (830) has been repor-
P-Picoline N-oxide (831) reacts with aryl isocyanates to form isomeric
H Et
H OAc H Me02C H
(818) (819) (820)
B. Nader, R. W. Franck, and S. M. Weinreb, J. A m . Chem. SOC.,1980,102, 1153.

508 0. Tsuge, K. Uneo, and K. Oe, Chem. Lett., 1979, 1407.
509 L. Garanti and G. Zecchi, J. Chem. SOC.,Perkin Trans. 2, 1979, 1176.
510 G. Schmitt and B. Laude, Tetrahedron Lett., 1978, 3727.
5" N. P. Peet and P. B. Anzeveno, J. Heterocycl. Chem., 1979, 16,877.
Five-Membered Ring Systems 217
N=N
0"'N
I
0-
. ,
(A) R' = Me, R2 = H (833) R' = H, R2 = Me
(B) R' = H, R2 = Me
Reagents: i, ArNCO
Scheme 9
oxazolopyridones (832) and (833); these arise by [1,5]-carboxyl shifts from

nitrogen to carbon in the initial 1,3-dipolar cyclo-adducts shown in Scheme 9.'12
Isoxazolo[5,4-b]pyridines(834; R = Me, Et, or Pr) rearrange to oxazolo[5,4-
blpyridines (835) on irradiati~n.''~Thermolysis of the thione (836) results in
extrusion of sulphur and the formation of the urea (837) and the pyridotriaz-
inedione (838).514 Treatment of o-phenylenediamine with tetrakis(brom0-
methy1)methane in DMF, in the presence of sodium hydride, affords the spiran
(839); the two additional carbon atoms in the product are supplied by the
solvent.''' 1,2,4-Triazolo[5,1-c][1,4]benzoxazines(841; R = H, Me, Et, or Ph)
are obtained by base-catalysed double cyclization of the hydrazones (840).'16
'12 T. Hisano, M. Ichikawa, T. Matsuoka, H. Hagiwara, K. Muraoka, T. Komori, K. Harano, Y. Ida, and
A . T. Christensen, Chem. Pharm. Bull., 1979,27,2261.
'13 C . Skotsch and E. Breitmaier, Chem. Ber., 1979,112, 3282.
'14 A . Ohsawa, H. Arai, and H. Igeta, Heterocycles, 1979, 12, 917.
'15 S. Srnolinski and A . Czarny, Bull. Chem. SOC.Jpn., 1979, 52, 930.
'16 N. Bizzozero, L. Garanti, and G. Zecchi, Synthesis, 1979, 909.
Rn;. N
(834) X = CPh, Y = N
(835) X = N, Y = CPh
11 Compounds containing Fused Five- and Seven-Membered Rings

and Five- and Eight-Membered Rings [(5,7) & (5,8)]
Treatment of the oxygenated biphenyl (842) with lead(1v) acetate affords the
complex benzofuran (843), as shown by X-ray analy~is.’~’The benzylidene-
isoindolinone (844) cyclizes to compound (845) in polyphosphoric acid.”’ The
novel 1,2-dihydroindolo[1,7-ab][ 1,5]benzodiazepines (847 ; R = H, Me, or Ph)
are formed by Bischler-Napieralski cyclization of the amides (846).5’9N-Acyl-
1,2-diazepines (848; R = Me, Ph, or OEt) react with tosylmethyl isocyanide to
give the pyrrolodiazepines (849).’*’ Condensation of NN’-diphenylacetamidine
(850) with l-phenylpyrrole-3,4-dicarbonyl dichloride results in the fused
methylenediazepinedione (851); an oxygen analogue is obtained from furan-3,4-
~ ~ ’imidazotriazepinone (853) has been prepared from
dicarbonyl d i ~ h l o r i d e .The
1,2-diamino-4-phenylimidazole(852) and ethyl a ~ e t o a c e t a t eThe . ~ ~reaction
~ of
2,4-dimethyloxazole (854) with dimethyl acetylenedicarboxylate affords the
oxazolo-azepine ( 8 5 5 ) in 2% yield.523 The propargyl ether (856) has been
converted into a derivative (857) of the novel 172,4-triazolo[2,3-d][1,4]benz-
oxazepine ring system by the action of ethanolic sodium eth~xide.’*~
’” F. R. Hewgill, D. G. Hewitt, G. B. Howie, C. L. Raston, R. J. Webb, and A. H. White, J. Chem. SOC.,
V. Scartoni, R. Fiaschi, S. Catalano, I. Morelli, and A. Marsili, J. Chem. SOC.,Perkin Trans. 1, 1979,
1547.
’19 E. J. Glamkowski and J. M. Fortunato, J. Heterocycl. Chem., 1979, 16, 865.
520
D. Harris, S. Syren, and J. Stre;;:., Tetrahedron Lett., 1978, 4093.
521 H. W. Heine, D. W. Ludovici, J. A. Pardoen, R. C. Weber, 11, E. Bonsall, and K. R. Osterhout, J.
Org. Chem., 1979, 44, 3843.
522 R. Bruckner, J. P. Lavergne, and P. Viallefont, Liebigs Ann. Chem., 1979, 639.
523 L. B. Medvedskaya, G. Ya. Kondrateva, and N. V. Bykanova, Zzv. Akad. Nauk SSSR, Ser. Khim.,
1979,1613.
524 H. Moskowitz, A. Mignot, and M. Miocque, J. Heterocycl. Chem., 1979,16, 1077.
Five-Membered R i n g Systems 219
H,C-C, //NPh + E\
N P h
NHPh ClOC
E = C02Me (856) (857)
Ninhydrin (858)reacts with p-cresol in the presence of zinc chloride to yield the
eight-membered lactone (859).’” Generation of the carbene (860) from the
corresponding diazopyrazole in the presence of benzene derivatives PhR (R =
MeO, Me, C1, CN, or NO,) results in mixtures of isomeric substitution products
(861) and ring-expanded pyrazolo-azocines (862); electron-withdrawing substi-
tuents enhance the formation of the latter (cf. p. 158).”6 The oxadiazoloben-
zodiazocinone (864) is formed by the action of phosgene on the N-oxide (863).’”
525 J. C. Roussey and B. Laude, C.R. Hebd. Seances Acad. Sci., Ser. C, 1979, 288, 225.
s26 W. L. Magee and H. Shechter, Tetrahedron Lett., 1979,4697.
527 H. Natsugari, K. Meguro, and Y. Kuwada, Chem. Pharm. Bull., 1979,27,2608.
d$H
0
&
0-
2
Ph
-N
PhN
12 Compounds containing Three or Four Fused Heterocyclic Rings

[(59595)9 (5,59619 (59597)9 (59697) and (5SS,6)1
The X-ray structure of the tricyclic phosphorus compound (865) has been
dete~mined.~"When a solution of benzimidazole in aqueous acetonitrile was
added to a mixture of calcium carbonate, thiophosgene, dichloromethane, and
water, there emerged o-phenylene di-isothiocyanate, together with a little of the
dibenzimidazolothiadiazinethione (866).52'The action of tetrazoles (867 ; R =
Me, Ph, PhCH2, PhCO, or C0,Et) on the chlorotetrazolopyrimidine (868) results
in the formation of triazolotetrazolopyrimidines (869), with extrusion of
nitrogen.530
Several ingenious syntheses of cyclazines have been carried out by Flitsch and
his colleagues. The pyrrolopyrrolidone (870) is converted into the salt (871) by
D. W. White, B. A. Karcher, R. A. Jacobson, and J. G . Verkade, J. A m . Chem. Soc., 1979, 101,

492 1.
529 R. Hull, Synth. Commun., 1979,9, 477.
530 A. Konnecke, C. Richter, and E. Lippmann, Z. Chem., 1979.19, 101.
the Vilsmeier-Haack reagent; treatment of the corresponding perchlorate with
dimethyl acetylenedicarboxylate yields the cycl[3.2.2]azine (872).'3' The
cycl[4.2.2]azinium perchlorate (874), which has a periphery of ten 7r-electrons
and is diatropic, was obtained by the action of ethoxyethylene on the salt (873).532
The aldehyde (875) reacts with the phosphorane Ph3P=C(CO2Bu')CH2CO,Bu'
to furnish the cyc1[4.3.2]azine derivative (876); the t-butyl ester of glycine affords
the aza-analogue (877). Both compounds form iron tricarbonyl complexes when
treated with di-iron e n n e a ~ a r b o n y l .When
~ ~ ~ the sodium+ salt of pyrroke-2-
aldehyde is heated with the bis-phosphonium di-iodide Ph,P-CH=CH-PPh,
21- in xylene, the tetracyclic compound (878) is produced. The reader is
recommended to consult the original paper for an explanation of this extra-
ordinary reaction.534
(210, (874)
(873)
(876) X = CCOZBut (879)

(877) X = N
Fusion of 2-fluoroimidazole yields the tri-imidazolotriazine (879); if 4-substi-
tuted 2-fluoroimidazoles are employed, mixtures of three of the four possible
isomeric products are formed.535
531 W. Flitsch, J. Koszinowski, and P. Witthake, Chern. Ber., 1979, 112, 2465.
532 W. Flitsch and E. R. Gesing, Tetrahedron Lett., 1979, 3405.
533 W. Flitsch and E. Mukidjam, Chem. Ber., 1979, 112, 3577.
534 W. Flitsch and E. R. Gesing, Chern. Ber., 1980, 113, 614.
535 Y . Takeuchi, K. L. Kirk, and L. A. Cohen, J. Org. Chern., 1979, 44,4243.
Six-Membered Ring Systems
BY S. D. CARTER, G. W. H. CHEESEMAN & G. P. ELLIS
PART I: Systems containing Nitrogen by S. D. Carter and G. W. H. Cheeseman
1 Introduction
This Report follows the pattern established by the previous Reporter in Volume
1. The section dealing with fused 5,6-systems is chiefly concerned with the
chemistry of purine and purine analogues and that on fused 6,6-systems with the
chemistry of pteridines and flavins. Within the discussion of a given ring system,
reference is made to synthetic methods before physical properties and reactivity.
Where appropriate, fully aromatic compounds are discussed before those of an
increased level of saturation. Because of the limits of space imposed on the Senior
Reporters of this volume, it has been necessary to omit reference to much
interesting work.
2 Reviews
The past year has seen the publication of Comprehensive Organic Chemistry,’
one volume of which contains much information on the six-membered ring
systems to be reviewed in this article; a monograph on the chemistry of condensed
pyrazines has also appeared.2 Reviews on 1,4-thia~ines,~ 1,3-ben~othiazines,~
pyridazines,’ benzo[c]~innolines,~ quina~olines,~purines,’ pyrrolo[3,2-c]quino-
lines,9 1,lO-phenanthroline and its complexes,1o polyaza-phenanthrenes,’l and
1,9- and 1,lO-diaza-anthracenes’* have been published. Other specialist reviews
are devoted to catalytic methods of obtaining pyridine bases;13 pyridine N-
the stereochemistry of quinolizines, indolizines, and pyrrolizines;’’
benzothiazinone dioxides;16 2-quinazolones and their cyclic homologues (e.g.
‘Comprehensive Organic Chemistry’, Vol. 4, ed. P. G. Sarnrnes, Pergamon, Oxford, 1979.
* G. W. H. Cheeseman and R. F. Cookson, Chem. Heterocycl. Compd., Vol. 35.
’ R.J. Stoodley, Adv. Heterocycl. Chem., 1979,24,294.
J. Szabo, Chem. Heterocycl. Compd. (Engl. Transl.), 1979,15,239.
M.Tisler and B. Stanovnik, Adu. Heterocycl. Chem., 1979,24,363.
J. W.Barton, Adv. Heterocycl. Chem., 1979,24, 152.
’ W. L. F. Armarego, Adv. Heterocycl. Chem., 1979,24,1.
G. Shaw, Rodd’s Chem. Carbon Compd. (2nd edn.), 1979,Vol. IVL, p. 1.
M.A. Khan and J. F. da Rocha, Heterocycles, 1979,12,857.
lo W. Sliwa, Heterocycles, 1979,12,1207.
W.Sliwa and H. Zamarlik, Heterocycles, 1979,12,529.
’’ J. A. Bajgrowicz and W. Czuba, Wiad. Chem., 1979,33,375.
l3 I. Ya. Lazdin’sh and A. A. Avots, Chem. Heterocycl. Compd. (Engl. Transl.),1979,15,823.
l4 R.A. Abramovitch, Lect. Heterocycl. Chem., 1980,5 , 15.
I. M. Skvortsov, Russ. Chem. Rev. (Engl. Transl.), 1979,48,262.
l6 P. Catsoulacos and Ch. Camoutis, J. Heterocycl. Chem., 1979,16,1503.
223
benzodia~epinones);~~ 4-q~inazolones;'~ cyanuric acid;" the physicochemical
aspects of purines;2onucleoside synthesis;21nucleosides, nucleotides, and nucleic
acids;22 pteridines, alloxazines, flavins, and related fused
pyrimidines with oxido-reductive potential;24 and nitrogen-selenium
heterocycle^.^^ Reviews dealing with small synthons for the construction of
six-membered rings demonstrate the utility of formamide acetals,26 nitroacetic
acid and its hexamethylenetetramine,28 P - e n a m i n o - e ~ t e r s , ~ ~
heterocumulenes conjugated with a carbonyl group (e.g. acyl is~cyanates),~'
iminodienophiles (e;g. C13CCH=NTs),31 and 3-chloro-2-propeniminiumsalts
(R'CC1=CHCR2=NR3R4 X-).32More general topics reviewed are the concept
of .rr-deficiency in the chemistry of heteroaromatic developments
in arylnitrene chemistry,34 the chemistry of Reissert reactions of
aromatic heterocycles involving the catalytic action of cyanide the photo-
oxygenation of nitrogen heterocycle^,^^ and the biosynthesis of plant alkaloids
and nitrogenous microbial metabolite^.^' Valuable summaries of the synthetic
applications of pyridinium salts for the transformation of primary amines into
other f u n ~ t i o n a l i t i e sand
~ ~ of synthetic reactions based on 2-halogenated
pyridinium, benzoxazolium, benzothiazolium, and pyrimidinium salts4' have
appeared.
3 Azines and their Hydro- and Benzo-derivatives

Pyridines.-Synthesis. A full report on the synthesis of pyridones from acetylenic
alcohols and N-cyanopyrrolidine, noted in Volume 7 of 'Aromatic and
Heteroaromatic Chemistry', has a ~ p e a r e d . ~ '
2-Imino-1,2-dihydropyridines (1)
l7 A . V. Bogat-skii and S. A. Andronati, Chem. Heterocycl. Compd. (Engl. Transl.), 1979, 15, 583.
la V. M. Prashad and A. P. Bhaduri, Chem.-Ztg., 1979,103,277.
l9 J. A. Burakevich, Kirk-Othmer Encycl. Chem. Technol. (3rd edn.), 1979,7, 397.
2o J. H. Lister, Adu. Heterocycl. Chem., 1979, 24, 215.
21 F. Dumont, J. L. Barascut, C. Chavis, and J. L. Imbach, Lect. Heterocycl. Chem., 1980, 5, 27.
22 D. S. Jones, Rodd's Chem. Carbon Compd. (2nd edn.), 1979, Vol. IVL, p. 117.
23 K. Ohta, R. Wrigglesworth, and H. C. S. Wood, Rodd's Chem. Carbon Compd. (2nd edn.), 1979
Vol. IVL, p. 237.
24 F. Yoneda, Lect. Heterocycl. Chem., 1980, 5, 73.
25 I. Laiezari, A. Shafiee, and M. Yalpani, Adu. Heterocycl. Chem., 1979, 24, 109.
26 R. F. Abdulla and R. S. Brinkmeyer, Tetrahedron, 1979, 35, 1675.
27 M. T. Shipchandler, Synthesis, 1979, 666.
28 N. Blazevic, D. Kolbah, B. Belin, V. Sunjic, and F. Kajfez, Synthesis, 1979, 161.
29
H. Wamhoff, Lect. Heterocycl. Chem., 1980,5, 61.
30 0. Tsuge, Heterocycles, 1979, 12, 1067.
31 S. M. Weinreb and J. I. Levin, Heterocycles, 1979, 12, 949.
32 J . Liebscher and H. Xartmann, Synthesis, 1979, 241.
33 A. F. Pozharskii, Chem. Heterocycl. Compd. (Engl. Transl.), 1979, 15, 939.
34 B. Iddon, 0. Meth-Cohn, E. F. V. Scriven, H. Suschitzky, and P. T. Gallagher, Angew. Chem., Int
Ed. Engl., 1979, 18, 900; H. Suschitzky, Lect. Heterocycl. Chem., 1980, 5 , 1.
35 F. D. Popp, A d o . Heterocycl. Chem., 1979, 24, 187.
36 E. Hayashi and T. Higashino, Heterocycles, 1979, 12, 837.
37 M. V. George and V. Bhat, Chem. Reu., 1 9 7 9 , 7 9 , 4 4 7 .
38 R. B. Herbert, Rodd's Chem. Carbon Compd. (2nd edn.), 1979, Vol. IVL, p. 291.
39 A. R. Katritzky, Tetrahedron, 1980, 36, 679.
40 T. Mukaiyama, Angew. Chem., Int. Ed. Engl., 1979, 18, 707.
41 L. E. Overman, S. Tsuboi, J. P. Ross, and G. F. Taylor, J. A m . Chem. SOC.,1980,102,747; R. K
Smalley, in 'Aromatic and Heteroaromatic Chemistry', ed. H. Suschitzky and 0. Meth-Cohr
(Specialist Periodical Reports), The Chemical Society, London, 1979, Vol. 7, p. 147.
Six-Membered Rings: Systems containing nitrogen 225
have been prepared by the nickel(0)-catalysed reaction of two molecules of
alkyne and one of carbodi-imide (Scheme l).42
Isoquinolinium salts (2) derived from a-bromo-ketones undergo Michael
addition to ap-unsaturated ketones in acetic acid, in the presence of ammonium
acetate, to give 2,4,6-triaryl-pyridines (3) in yields ranging from 40 to 60%
-
(Scheme 2).43
i R f i
PhN=C=NPh + 2RCrCR R
N NPh
Ph
( 1 ) R = alkyl or aryl
Reagents: i, Bis(cyc1o-octa-1,s-diene)nickel(O), PPh3
Scheme 1
Ar' Ar3 Ar' Ar

(2) (3)
Reagents: i, NH,OAc, HOAc
Scheme 2
A 2,4,6-trisubstituted pyridine (5) also results from the reaction of the dianion
of 2-methylpropene (4) with two molecules of benzonitrile (Scheme 3).44 A new
route to 2-aryl-pyridines is discussed on p. 273.
Either 4- or 6-hydroxypyridones may be formed by the base-catalysed reaction
of diketen with primary amines. Weak bases such as NN-dimethylaniline favour
the production of the 6-hydroxy-compounds (Scheme 4).45
Scheme 3
RNH, -!+ RNHCOCH,COMe - I
HO
R
+ Me CcMe
R
Reagents: i, H * c ~, base
o
Scheme 4
42 H. Hoberg and G. Burkhart, Synthesis, 1979,525.
43 R. S. Tewari and A. K. Dubey, J. Chem. Eng. Data, 1980,25,91.
44 R. B. Bates, B. G. Gordon, P. C. Keller, J. V. Rund, and N. C. Mills, J. Org. Chem., 1980,45,168.
45 P. Dirnroth and V. Radtke, Liebigs A n n . Chem., 1979, 769.
Improved yields of 4-oxonicotinic acids are obtained from P-keto-esters and
0-aminocrotonates by their reaction in boiling xylene in the presence of
molecular sieves, rather than by thermal c y ~ l i z a t i o nThe
. ~ ~ choice of conditions
is also important in the condensation of methyl cyanoacetate (6) and methyl
methoxymethyleneacetoacetate (7). At low concentrations of sodium rnethoxide,
good yields of the 2-pyridone (8) are obtained; higher concentrations of base
favour formation of an a-pyrone (Scheme 5).47
The use of 1,1,3,3-tetramethoxypropane(10) for the synthesis of 2,3-disub-
stituted pyridines is further exemplified by the two-stage preparation of
the 2-bromo-3-(alkylthio)pyridine (11)from (trifluoromethy1thio)acetonitrile (9)
(Scheme 6).48
Me02C MeOCH,IC02Me NaOMe ,Me02C/ C0,Me
'I+ Me
CN
0
' Me O N
(6) H
(7)
(8)
Scheme 5
/ SCF3 +
C\H2
CN
CoMe-
OMe
OMe
O S C F 3
Br
(10)
Reagents: i, Ac,O, ZnC1,; ii, HBr
Scheme 6
Ph
PhfiPh
s-s
+ NH,COCH,CN --+
Ph
c10,- H
(12) (13)
Scheme 7
3,5-Diphenyl-1,2-dithiolium perchlorate (12) has been employed as a 1,3-
dicarbonyl equivalent for pyridine synthesis, as illustrated by its reaction with
cyanoacetamide to give the cyanopyridone (13) (Scheme 7).49
The reaction of 3-imino-N,1,3-triphenylprop-l-enarnine (14) with dimethyl
acetylenedicarboxylate (DMAD) gives the pyridone (15). If the enamine is
P-disubstituted, as in compound (16), then initial attack occurs on the imine
nitrogen rather than the enamine carbon. Electrocyclization followed by loss of
aniline then yields the pyridine (17) (Scheme 8).50
Several pyridine syntheses involving [4 + 21 cycloaddition reactions have been
reported. Thus when trichloro-1,2,4-triazine(18) is heated with alkenes, 2,6-
dichloropyridines (19) are formed in 75-80% yield (Scheme 9)."
46 0 . Makabe, Y. Murai, and S. Fukatsu, Heterocycles, 1979, 13,239.
47 S. R. Baker, L. Crombie, R. V. Dove, and D. A. Slack, J. Chem. SOC.,Perkin Trans. I , 1979, 677.
48 G. S. Ponticello, R. D. Hartman, W. C. Lumma, and J. J. Baldwin, J. Org. Chem., 1979, 44, 3080.
49 I. Shibua, Bull. Chem. SOC.Jpn., 1979, 52, 1235.
J. Barluenga, M. Tomas, S. Fustero, and V. Gotor, Synthesis, 1979, 345.
51 M. G. Barlow, R. N. Haszeldine, and D. J. Simpkin, J. Chem. SOC.,Chem. Commun., 1979, 658.
Six-Membered Rings: Systems containing nitrogen
Yh Ph-NHPh
E
-
-MeOH ph510
Ph/
HN
0
227
(15)
Ph
Scheme 8
2-Azabutadienes, e.g. (20), variously undergo cycloaddition
with dienophiles to form, after aromatization, substituted pyridines, e.g. (21).
With unsymmetrical dienophiles such as acrylonitrile, the reaction is regiospecific
(Scheme 10).
CI CI CHMe,
-HCI
Ci (19) (20) (21) Z = C02Me or CN
(18) Reagents: i, H,C=CHZ
Scheme 9 Scheme 10
A new class of dienes (22) has been found to undergo cycloaddition with nitriles
to give amino-pyridines (23) (Scheme 1l).54
4-Dimethylaminobuta-1,3-diene-l,l-dicarbonitriles (24), prepared as shown
in Scheme 12, have been cyclized, by reaction with ammonia at 150°C, to the
corresponding 2-amino-3 -cyano-pyridines (25) .55
1-"N-Labelled nicotinamide (27) has been obtained in high yield by the
reaction of the pyridinium salt (26) with labelled ammonium chloride (Scheme
13).56
NMe,
AMe, NMe,
Me ,C4
X-
k,,
(22) X=C1 or I
7
L
(23) R = M e or CH=CH2
Reagents: i, RCN; ii, Et3N
Scheme 11
52 Y. Nomura, Y. Takeuchi, S. Tomoda, and M. M. Ito, Chem. Lett., 1979, 187.

53
R. Gompper and W. Heinemann, Angew. Chem., Int. Ed. Engl., 1980,19, 217.
54 M. Gillard, C. TKint, E. Sonveaux, and L. Ghosez, J. Am. Chem. Soc., 1979,101,5837.
55 G. Ege, 0. H. Frey, and E. Schuck, Synthesis, 1979, 376.
56
N. J. Oppenheimer, T. 0. Matsunaga, and B. L. Kam, J. Labelled Compd. Radiopharm., 1978,
15, 191.
228 Heterocyclic Chemistrv
R2
\ R'
NC
NC
\
/c=c \
/
CH2R2
R'
i, ii
___*
NC\
NC
/c=c \
(24)
/C=CHN Me2
R'
iii
___,
-NHMe,
R
20:,
N
Reagents: i, LDA, THF, at -65 "C; ii, CICH=NMe,CI ; iii, NH,, at 150 "C
Scheme 12
(26)
Reagents: i, "NH,CI, Et,N
Scheme 13
Isoxazolopyridines (30) are conveniently prepared from 3-ethoxy-acroleins

(29) and 5-amino-isoxazoles (28). The reaction proceeds by initial 1,4-addition
of the amine to the a@-unsaturated aldehyde (Scheme 14).57
Scheme 14
Thiadiazolopyridines, e.g. (32), result from the base-catalysed reaction of
alkylamines with 3,4-diaroyl-thiadiazoles,e.g. (3l), (Scheme 15). The yield of
compound (32) is 88%, but the corresponding oxadiazolopyridine is only
obtained in 13% yield. As many diaroyl-substituted five-membered heterocycles
are easily obtainable from 1,3-dipolar cyclization reactions with diaroyl-alkynes,
this reaction may provide a useful method for preparing fused pyridine~.~'
Me2FCH2Ph
I
+
(31)
Reagents: i, PhCH,NH,, DBU
Ph
(32)
0 N
(33)
Scheme 15
Reactions of Pyridines. Treatment of 4-isopropylpyridine with lithium aluminium
hydride, followed by electrophilic reagents, leads to side-chain- rather than
ring-substitution products. For example, the 4-pyridylpropane (33) is formed
57 C. Skotsch, I. Kohlmeyer, and E. Breitmaier, Synthesis, 1979, 449.
58 S. Mataka, K. Takahashi, and M. Tashiro. Synthesis, 1979, 687.
from 4-isopropylpyridine by sequential treatment with lithium aluminium
hydride and benzyl ~hloride.’~A laboratory apparatus has been described for the
conversion of 4-methyl- into 4-cyano-pyridine by a process that is known
technically as ammoxidation.60
2-(Phenacy1)pyridines are obtained in high yields (70-99%) by the reaction of
2-(trimethylsilylmethy1)pyridine with paru-substituted benzonitriles, using LDA
in THF at -75°C.6* The reaction of the 4-lithio-derivative of the 2-(3’-
pyridy1)oxazoline (35) with electrophiles yields, after hydrolysis, 4-substituted
pyridine-3-carboxylic acids (36); the reaction of (35) with Grignard reagents
yields 1,4-dihydropyridines (34) (Scheme 16).62
Carboxamides are formed by treatment of 3-hydroxypyridine-2-carboxylic
acids with ammonia at high temperatures, and not, as previously reported,
3-aminopyridine-2-carboxylic The mercury compound (37), derived
from pyridine-2,3-dicarboxylic acid and mercuric oxide, undergoes ring-opening
with a variety of nucleophilic reagents (H2S, NaCN, KI) to give 2-substituted
pyridine-3-carboxylic acids (38) (Scheme 17).64
H (36)
Reagents: i, , E’ (E = electrophile); ii, aqueous HCI; iii, RMgX

Scheme 16
do
-0;””
N
(37)
Hg
N
(38) X = SH, CN, or I [21-33°/0]

Scheme 17
High yields (90 and 86%) of 2-chloro- and 2-bromo-pyridine are obtained by
low-temperature (0-5 “C) halogenation of a palladium(I1) chloride complex of
~ y r i d i n e 2-chloropyridine
;~~ is converted into 2-bromopyridine by its reaction
with gaseous hydrogen bromide.66 A quantitative conversion of 2-chloro- into
2-methyl-pyridine is achieved by its reaction with methylmagnesium bromide in
the presence of a catalyst, readily prepared from 2-chloropyridine and
59 C.-S. Giam, T. E. Goodwin, K. F. Rion, and S. D. Abbott, J. Chem. SOC.,Perkin Trans. 1, 1979,
3082.
60
C.-H. Wang, F.-Y. Hwang, and J.-M. Horng, Heterocycles, 1979, 12, 1191.
61 T. Konakahara and Y. Takagi, Heterocycles, 1980,14, 393.
62 A. I. Meyers and R. A. Gabel, Heterocycles, 1978, 11, 1130.
63 G . G. I. Moore, A. R. Kirk, and R. A. Newmark, J. Heterocycf. Chem., 1979,16,789.
64 T. Takahashi, Chem. Pharm. Bull., 1979,21, 2473.
65 S. Paraskewas, Synthesis, 1980, 378.
66 Seitetsu Chem. Ind., J. Synth. Methods, 1979, 5 , Abstr. 77 882U.
230 Heterocyclic Chemistr)'
tetrakis(triphenylph~sphine)nickel(o).~~Heterocyclic halides, including 2-
bromopyridine, are converted into the corresponding thiols by reaction with
excess of acidified thiosulphate.68
An interesting ortho-aminophenylation reaction of reactive heterocycles is
exemplified by the conversion of 4-chloro-3-nitropyridine (39) into the (o-
aminopheny1)pyridone (40).69The ortho-ortho-linked product contrasts with the
previously discovered reaction of 2-chloro-3-nitropyridine, which, under the
same conditions, gives a para-para-linked product. This very rare ortho-ortho
benzidine-type rearrangement only occurs when a para-position is blocked, and
has also been carried out with appropriately substituted pyrimidine and benzene:
derivatives (Scheme 18).
Reagents: i, HONPhCO,CH,Ph, KOH

Scheme 18
An anomalous reaction occurs when 3-bromo-2-chloropyridine is treated with

n-butyl-lithium in T H F at -40 "C. After treatment of the reaction product with
ethanol, 50% of 2-chloropyridine, 10% of 2-bromopyridine, and 35% of
4-bromo-2-chloropyridine is ~ b t a i n e d . ~Further
' examples of the palladium-
catalysed alkenylation of P-halogeno-heterocycles have been reported. Thus 3-
substituted alkenylpyridines have been obtained in good yield from 3-iodopyri-
dine and 3-(alkenyl)quinolines,and 4-(alkeny1)isoquinolines have been prepared
~imilarly.~' The reaction of 3-substituted-2,6-dichloropyridineswith the dianion
of pentaethylene glycol yields nicotinic acid crown ethers that are of interest as
enzyme (NAD) models.72The photochemical reaction of 3-chlorotetrafluoro-
pyridine and ethylene yields 3-(2-chloroethyl)tetrafluoropyridine,in contrast to
pentafluoropyridine, which forms 1 : 1 and 1 :2-cyclo-adducts with ethylene.73
Photolysis of tetrachloro-4-(phenylthio)pyridine (41) gives the benzo-
thienopyridine (42); the reaction is envisaged as proceeding uia loss of the
3-chlorine followed by intramolecular homolytic arylation (Scheme 19).'"
Various routes to 4-bromo- and 4-iodo-tetrachloropyridine have been evalu-
ated75 and the thermal rearrangements of 4-allyloxy-tetrachloropyridines
~ most convenient preparation of the 4-bromo-compound involves
s t ~ d i e d . 'The
67 K. Isobe, Y. Nakamura, and S. Kawaguchi, Bull. Chem. SOC.Jpn., 1980, 53, 139.
68 W. 0. Foye, N. Abood, J. M. Kauffman, Y.-H. Kim, and B. R. Patel, Phosphorus Sulfur, 1980, 8 ,
205.
69 T. Sheradsky, E. Nov, and S. Avramovici-Grisaru, J. Chem. SOC.,Perkin Trans. 1, 1979, 2902.
70 M. Mallet and G. QuCguiner, Tetrahedron,1979, 35, 1625.
71 K. Edo, T. Sakamoto, and H . Yamanaka, Chem. Pharm. Bull., 1979,27, 193.
72 G. R. Newkome, T. Kawato, and A. Nayak, J. Org. Chem., 1979,44,2697.
73 M. G. Barlow, R. N. Haszeldine, and J. R . Langridge, J. Chem. SOC.,Chem. Commun., 1979,608.
74 J. Bratt, B. Iddon, A. G. Mack, H. Suschitzky, J. A. Taylor, and B. J. Wakefield, J. Chem. SOC.,
'' A. G. Mack, H. Suschitzky, and B. J. Wakefield, J. Chem. SOC.,Perkin Trans. 1, 1979, 1472.
76 B. Iddon, H. Suschitzky, and J. A. Taylor, J. Chem. SOC.,Perkin Trans. I, 1979, 2756.
Six-Membered Rings: Systems containing nitrogen 23 1
c1 \
CI&
N
(41)
+ cC1I\f i C l
N
----+ clp
c1 \
N
(42)
Scheme 19
the reaction of pentachloropyridine with magnesium at low temperature (-75 "C)
and treatment of the resulting 4-pyridylmagnesium chloride with bromine.
Zerovalent platinum complexes, e.g. [Pt(PPh,),], catalyse the rearrangement of
(ally1oxy)pyridines to N-allyl-pyridones at relatively low t e m p e r a t ~ r e s . ~ ~
The gas-phase equilibrium between 2-hydroxypyridine and 2-pyridone
favours the hydroxy-form, but in the equilibrium between 2-hydroxy-
pyridine N-oxide and N-hydroxy-2-pyridone, the major tautomer is the hydroxy-
p y r i d ~ n e .Bicyclic
~~ adducts between 2-pyridones and dimethyl acetylene-
dicarboxylate, unobtainable at atmospheric pressure, have been obtained at
10-15 kbar.79 A novel route to N-hydroxy-2-pyridone involves the trimethyl-
silylation of 2-pyridone followed by oxidation of the resulting 2-(trimethyl-
sily1oxy)pyridine with the DMF complex of molybdenum pentoxide.8"
p-Nitro-phenols (45) and nitro-acetamides (46) are formed from the reaction
02No:2
of 3,5-dinitro-2-pyridones (43) with the sodium salts of P-keto-esters (44)
(Scheme 20).81
R2oCO2Et
+ R2CH2COCHNaC0,Et +
+ 7H2N02
(44) CONHR'
R' NO2 (46)
(43) R' = alkyl or aryl; R2 = H or CO,Et (45)
Scheme 20
Analogues of flavipucine (47; R = CH2CHMe2)have been prepared; maximum
antibacterial activity is found with an octyl side-chain.82Much work continues to
be published on the cycloaddition reactions of betaines of type (48), which react
with alkenes across positions 2 and 6 and with dienes across positions 2 and 4.
I
(47) COAr
(48) Ar = 4-C1- or 4-Br-C6H4
77 G. Balavoine and F. Guibe, Tetrahedron Lett., 1979, 3949.
78 R. S. Brown, A. Tse, and J. C. Vederas, J. A m . Chem. SOC.,1980,102, 1174.
79 K. Matsumoto, Y. Ikemi-Kono, T. Uchida, and R. M. Acheson, J. Chem. SOC., Chem. Commun.,
1979,1091.
S. A. Matlin, P. G. Sammes, and R. M. Upton, J. Chem. SOC., Perkin Trans. 1, 1979, 2481.
81 E. Matsumura, M. Ariga, and Y. Tohda, Tetrahedron Lett., 1979, 1393.
82 N. N. Girotra, A. A. Patchett, S. B. Zimmerman, D. L. Achimov, and N. L. Wendler, J. Med.
Chem.,1980,23,209.
The /3- (aroy1)vinyl substituent is chosen as an activating and easily removable
substi tuen t .83
2,5- and 3,5-Dimercaptopyridine have been prepared from 5-amino-2-chloro-
and 3,5-dihydroxy-pyridineY~ e s p e c t i v e l y .The
~ ~ *route
~ ~ to the 3,5-dimercapto-
compound (49) is illustrated in Scheme 21. A new reagent (2-C5H4NSCOC1),
prepared from 2-mercaptopyridine and phosgene, is capable of converting acids
into pyridine-2-thiol esters (2-CsH4NSCOR) under extremely mild conditions;
these esters are useful, e.g., in peptide synthesis.86
Ring-opening of the dichloride (50) with barium hydroxide, followed by
ring-closure, gives 2-aminopyridine-3-carboxaldehyde (51) in 70% yield
(Scheme 22).87
S S 0 0
H O O O H II
Et,NCO ,-’OCNEt, II
Et,NCSf]SCNEt2 II iii Hsn!’”
-
~ ii
+
N n
N l1 N N
(49)
Reagents: i, Et,NC(=S)CI; ii, heat, at 230°C; iii, N,H,, H,O
Scheme 21
$iH2
N
CH,Ph
(50)
2c1-
O C H O
N
(51)
NH2 P
\
P
-
h
SCN
Ph \ + 6 Ar
Ph
SCN
Reagents: i, aqueous Ba(OH), (52) (53)
Scheme 22
An improved, mild procedure for the conversion of pyrylium salts into
pyridinium salts, involving successive catalysis by base (Et,N) and acid (AcOH),
has been announced.88A significant improvement in the yields of aryl thiocyan-
ates from aryl-amines is achieved by pyrolysis of the tricyclic pyridinium
thiocyanates (52) rather than of the corresponding N-substituted 2,4,6-triphenyl-
pyridinium thiocyanates (53).89In general, the ease of thermal decomposition of
an N-substituted pyridinium cation depends strongly on the steric requirements
of the groups in the 2- and 6-positions of the pyridinium ring. A valuable
summary of the considerable number of transformations of functional groups
that involve the intermediate formation of pyridinium salts from primary amines
has appeared.39
The regiospecific reaction of the pyridinium salt (54) with a wide range of
nucleophiles gives 4-substituted pyridines (56) after thermolytic or photolytic
83 A. R. Katritzky, S. Rahimi-Rastgoo, G. J. Sabongi, and G. W. Fischer, J. Chem. Soc., Perkin Trans.
I, 1980, 362.
84 K. Krowicki, Pol. J. Chem., 1979, 53,889.
85 K. Krowicki, Pol. J. Chem., 1979, 53, 503.
86 E. J. Corey and D. A. Clark, Tetrahedron Lett., 1979, 2875.
87 W.-H. Guendel, Z. Naturforsch., Teil B, 1979, 34, 1019.
A. R. Katritzky, R. H. Manzo, J. M. Lloyd, and R. N. Patel, Angew. Chem., Int. Ed. Engl., 1980,
19,306.
A. R. Katritzky and S. S. Thind, J. Chem. SOC.,Perkin Trans. 1, 1980, 865.
0 N
I
Nut-
+
Nut
6 I
t
MeoMH
MeQMe
0
(54)
""OM'
(55)
0
- 0
Nuc = alkyl, CR'R*COalkyl, CR'R2N02,S-alkyl, S-aryl,

1-benzimidazolyl, or 1-benzotriazolyl
Scheme 23
decomposition of the resulting adducts ( 5 5 ) . Harder nucleophiles attack at the
2-position (Scheme 23).90*91
Pyridinium salts of type (57) are smoothly converted into N-substituted
pyridones (58) on reaction with pentyl nitrite and sodium methoxide, in an
average yield of 64% (Scheme 24).923-Phenacylpyridinium salts, e.g. (59), react
with hydrazine and potassium hydroxide to give 4-alkyl-6-phenylpyridazines, e.g.
(60), by a process involving ring-opening, ring-closure, and Wolff-Kishner
reduction (Scheme 25).93
R=alkyl or Ph
Reagents: i, pentyl nitrite, NaOMe
Scheme 24
Scheme 25
Pyridinium toluene-p-sulphonylmethylide (62), generated in situ from the

pyridinium salt (61), serves as an equivalent of formyl anion, and, in the presence
of an alcohol, it undergoes 1,4-addition to N-substituted maleimides to give
(alkoxymethy1ene)succinimides (63). The protected aldehyde is liberated by
treatment with hydrobromic acid (Scheme 26).94
90 A. R. Katritzky, H. Beltrami, J. G. Keay, D. N. Rogers, M. P. Sarnmes, C. W. F. Leung, and C. M.
Lee, Angew. Chem., Znt. Ed. Engl., 1979,18, 792.
C. W. F. Leung, M. P. Sammes, and A. R. Katritzky, J. Chem. SOC.,Perkin Trans. 1, 1979, 1698.
92 A. R. Katritzky and M. Shhnta, J. Chem. SOC., Chem. Commun., 1979, 552.
93 M. M. Baradarani and J. A. Joule, J. Chem. SOC.,Perkin Trans. 1, 1980, 72.
94 R. A. Abrarnovitch, S. S. Mathur, D. W. Saunders, and D. P. Vanderpool, Tetrahedron Lett. 1980,
21,705.
0 20
\+
N
\+
N
5
R'OCH
C H ,SO,Tol CH SO2Tol 0
(61) (62) (63)
Reagents: i, Et,N; ii, 00 0 , R1OH

R Scheme 26
Various new procedures have been reported for the reduction of pyridine
N-oxides, including the use of TiC14with NaBH4;95of (MeO),P with hv;96of SO,
generated in situ ;97 and of MoC1, with zinc Irradiation of pyridine N-oxide
in the presence of sodium hydroxide yields the anion of 5-hydroxypenta-2,4-
dienenitrile; if the irradiation is carried out in the presence of secondary amines,
derivatives of 5-aminopenta-2,4-dienenitrile are
Thermolysis of N-oxides of type (64) yields pyridyl ethers (65); on cleavage
with hydrazine, these give a catechol (67) and 2-hydrazino-5-nitropyridine (66).
In addition to the ortho-substituted phenol (65), thermolysis (if R = H) also gives
a small amount of para-substituted product. Since the starting materials can be
prepared from the reaction of 2-chloro-5-nitropyridine and a phenol, followed
by N-oxidation, this represents overall a four-stage process by which a phenol
can be converted into a catechol (Scheme 27).*'()
02NQNHNH,
O 2 N Q o D - 02NrJo/OK- (66)
+
I
O- (64)
R = H, Me or C1
(65)
OH
HO \
OH
0"
Scheme 27 (67)
Dipolar cycloaddition of pyridine N-oxide to the cyclic alkyne (68), followed

by rearrangement, leads to the formation of the first reported 2H-azepine (69);
this undergoes thermal rearrangement to the 2-substituted pyridine (70)
(Scheme 28).'"'
Reduced Pyridines.-An important new method for synthesizing unstable
1-alkyl-1,2-dihydropyridines(74) involves thermolysis of the stable bicyclic
precursor (73). Compound (73) is obtained by alkylation of 2-azabicyclo-
95 S. Kano, Y. Tanaka, and S. Hibino, Heterocycles, 1980, 14, 39.
96 C. Kaneko, A. Yamamoto, and M. Gomi, Heterocycles, 1979, 12, 227.
97 B. F. Bonini, E. Maccagnani, G. Mazzanti, and P. Pedrini, Tetrahedron Lett., 1979, 1799.
98 S. Polanc, B. Stanovnik, and M. Tisler, Synthesis, 1980, 129.
Y9
0. Buchardt, J . J. Christensen, P. E. Nielsen, R. R. Koganty, L. Finsen, C. Lohse, and J. Becher,
Acta Chem. Scand., Ser. B, 1980, 34, 31.
loo P. G. Sammes, G . Serra-Errante, and A. C. Tucker, J. Chem. SOC.,Perkin Trans. 1, 1979, 1736.
A. Krebs, H. Colberg, U. Hopfner, H. Himling, and J. Odenthal, Heterocycles, 1979, 12, 1153.
s ~
Me2
l
N
I
+ ~ 99+
Me2
s N- -+ s
Me2
235
(68) 0- (69) (70)

Scheme 28
[2.2.0]hex-5-ene (72), itself derived from the readily accessible l-methoxycar-
bonyl-1,2-dihydropyridine(71) (Scheme 29).Io2
The reactions of the oxosulphonium ylides (75) with electrophilic alkynes give
products (76) that are formed as a result of [3,2]sigmatropic rearrangement of
the initial adducts. On mild heating, methanesulphenic acid is eliminated, and
ring-closure of the resulting azatrienes (77) gives dihydropyridines (78) in yields
of 54-62% (Scheme 3O).lo3
(71)
Reagents: i, h v ; ii, MeLi; iii, H 2 0 ; iv, alkylating reagent; v, thermolysis
Scheme 29
MefOCH,
Phyc,yCHZCH
H ,SOMe
[3,21
shirt' z
/N /N
Ar Ar Ar (76)
(75)
1 -MeSOH
Ar = Ph or 4-NO2C6H4;
Z = C0,Et o r COPh ArN
phgz
"laz/ Z
+-
Z
Ar H,
(78) (77)
Scheme 30
1-Methyl-1,2-dihydropyridinebehaves as an enamine rather than as a diene
at -10°C in its primary cycloaddition reactions with alkenes and alkynes. At
higher temperatures, the [2 + 21 cyclo-adducts, e.g. (79), are unstable, and the
more thermodynamically stable Diels-Alder endo- and em-adducts, e.g. (80) and
(81), are formed.104
The 2-substituted-1,2-dihydropyridines(82) form bicyclic products (83) by
addition of cyanogen azide to the 5,6-double bond; these aziridines are readily
P. Beeken, J. N. Bonfiglio, I. Hasan, J. J. Piwinski, B. Weinstein, K. A. Zollo, and F. W. Fowler,
J. A m . Chem. SOC.,1979,101,6677.
lo3 R. Faragher, T. L. Gilchrist, and I. W. Southon, Tetrahedron Lett., 1979, 4113.
B. Weinstein, L.-C. C. Lin, and F. W. Fowler, J. Org. Chem., 1980, 45, 1657.
(80) R' = H, R2 = C 0 2 M e
(81) R' = C02Me, R2 = H
opened to form the cyano-imines (84) (Scheme 31). This contrasts with the
exclusive addition of cyanogen azide to the 3,4-double bond of 2-alkyl-1,2-
dihydro- 1-me thoxycarbonyl-pyridines .'OS
The 1,2-dihydropyridine chromium tricarbonyl complex (85) has been con-
verted into the tetrahydropyridine (86) as shown in Scheme 32.'06 The endo-
peroxides of l-alkoxycarbonyl- 1,2-dihydropyridines, e.g. (87) react with carbon
nucleophiles such as enamines, in the presence of stannous chloride, to give
substitution products, e.g. (88) (Scheme 33)."'
H
R = Bun or Ph
Scheme 31
Reagents: i, MeCHCN Li'; ii, CF,CO,H; iii, I2

Scheme 32
HO..
Me0,C
C0,Me
(87) H
Reagents: i, SnCI,, indole (88)
Scheme 33
The photolytic reaction of vinylogous formamides of the type (89) and cyclo-
pentene yields 1,4-dihydropyridines (90) as shown in Scheme 34.'08 Low-
temperature (-50 "C)deprotonation of 1,4-dihydro-l-methylpyridine(91) with
T. A. Ondrus, E. E. Knaus, and C. S. Giam, J. Heferocycl.Chem., 1979,16,409.
J. P. Kutney, M. Noda, and B. R. Worth, Heterocycles, 1979, 12, 1269.
lo' M. Natsume, Y. Sekine, M. Ogawa, H. Soyagimi, and Y. Kitagawa, Tetrahedron Left., 1979, 3473.
'08 L.-F. Tietze and K. Bruggermann, Angew. Chem., Int. Ed. Engl., 1979, 18, 540.
trimethylsilylmethylpotassium yields the anion (92); an 87r system that is rnoder-

ately stable at -50°C. The reaction of (92) with methyl iodide affords an
approximately 1: 1 mixture of 1,2-dihydro-1,2-dimethyl- and 1,4-dihydro-l,4-
dimethyl-pyridine (93) and (94)(Scheme 35).lo9
The 1,4-dihydropyridine (95) undergoes an unusual reaction with electrophiles
to give the dearylated pyridine (96) and a 4-substituted dimethylaniline (97)
(Scheme 36).*1°
H
cAGM
to Me C0,Et +
X+ E t 0 2 C0/Z 2 E t
Me \ N + \
X
$I
(96) (97)
(95)
Ar = 4-Me2NC6H4;Xf= NOt, I f , 4-H03SC6H4N2+,HgOAc+, or (SCN)2
Scheme 36
The reducing properties of 1,4-dihydropyridinesare illustrated in Schemes 37

and 38. Sulphonium salts of type (99) can be reduced by transfer of hydride ion
from the dihydropyridine (98).ll1The synthetic utility of this reaction is limited
E t 0 2 C o C 0 2 E t + R'CH2S+ / R 2 X- + E t 0 2 C o C 0 2 E t + R'CH, +R2SR'

Me Me \ Me'\+ Me
Me
(99)
R3
Me '-
(98) Scheme 37
CN CN
hv / CONH2 1
+ EtC(CH,),COMe + + EtCH(CH,),COMe
I NO;
CH2Ph ,
CH Ph
(100) (101)
Scheme 38
lo' M. Schlosser and P. Schneider, Angew. Chem., Inr. Ed. Engl., 1979, 18, 489.
110
R. G. R. Bacon and B. A. Osuntogun, J. Chem. SOC.,Chem. Commun., 1979,1159.
"' T. J. van Bergen, D. M. Hedstrand, W. H. Kruizinga, and R. M. Kellogg, J. Org. Chem., 1979,44,
4953.
by the irreversible thermal isomerization of the 1,4-dihydro-compound to the
inactive 1,2-dihydropyridine. The cyano-nitro-ketone (101) undergoes a selec-
tive, light-promoted reaction with 1-benzyl-l,4-dihydronicotinamide(loo),
resulting in replacement of the nitro-group with hydrogen. In this case, an
electron-transfer chain mechanism rather than a hydride-transfer mechanism has
been proposed.' l 2
The synthetically useful 5,6-dihydropyridinium salts (102) are readily prepared
by the reaction of tetrahydropyridine N-oxides with trifluoroacetic anhydride.
They undergo reaction with cyanide ion at position 2 and with various sulphur
and nitrogen nucleophiles at position 4 (Scheme 39).'13
R' R4
-NcyJ
1
R2V-
R'X R3
R 2 q
CF,CO;
R' \
R3
(102)
R', R2, R3, R4 = H or alkyl; R5= Ph, PhCH2, or NMe,; X = S or NH
Scheme 39
N-Substituted tetrahydropyridines (104) are formed by hetero-Cope re-

arrangement of the imines (103) derived from methacrolein dimer. The tetra-
hydropyridines so obtained polymerize within one hour at room temperature. A t
higher reaction temperatures, retro-Diels-Alder products are obtained (Scheme
40).'14
xo
Me ,CHI
+ Me\
CH2
NR
R = alkyl or Ph
~
[250--300 "C] Me@e
(103)
NR
[ ~ o ~ - ~ ~ oMeQMe
"~I,
R
(104)
CHO
Scheme 40
Treatment of l-methy1-1,2,3,6-tetrahydropyridine(105) with base gives
l-methyI-1,2,3,4-tetrahydropyridine(106). The enamine (106) is estimated to
be at least 4.0 kcal mol-' more stable than the allylamine (105) (Scheme 41).'15
Irradiation of (105) with light of wavelength 185 nm results in the formation of
buta-1,3-diene and the cyclic trimer (107). At 10% conversion, the yields of
butadiene and H2C=NMe monomer are 74 and 22% respectively.'16
n
MeN NMe
Me
(105)
Me
(1 06)
0
N
Me
Reagents: i, KOBu', DMSO
Scheme 41
'12 N. Ono, R. Tamura, and A. Kaji, J. A m . Chem. SOC.,1980,102, 2851.
D. S. Grierson, M. Harris, and H.-P. Husson, J. A m . Chem. Soc., 1980, 102, 1064.
K. B. Lipkowitz, S. Scarpone, D. McCullough, and C. Barney, Tetrahedron Lett., 1979, 2241.
'15 P. Beeken and F. W. Fowler, J. Org. Chem. 1980,45, 1336.
'16 R. Srinivasan, J. Studebaker, and K. H. Brown, Tetrahedron Lett., 1979, 1955.
The two trimeric forms of A'-piperideine (2,3,4,5-tetrahydropyridine)have

been obtained in excellent yield from 1-formyl-2-methoxypiperidine.' l 7 The
reaction of A'-piperideine (108) with electron-deficient alkenes gives dimeric
products (109) that are notable for their N-alkylated structures (Scheme 42).l18
0 N
(108)
+ H,C=CHZ +
Z = C02Me or CN
q-cJ
ZCHZCHZ
(109)
N
CH,CH,Z
Scheme 42
2-Substituted piperidines have been obtained from A'-piperideine as shown in

Scheme 43. An 85 : 15 mixture of the erythro- and threo-forms of the carbinol
(111) is formed;'" in the synthesis of (dl)-anabasine (110; R = 3-pyridyl), the
use of t-butyl-lithium to form 3-lithiopyridine from 3-bromopyridine is recom-
rnended.lz0 A1-Piperideine is conveniently generated in solution by the action of
potassium superoxide and a crown ether on an ethereal solution of N-
chloropiperidine.
Reagents: i, HCN; ii, PhCOCl; iii, LDA, PhCHO; iv, NaBH,; v, RLi
Scheme 43
Reagents: i, Hg(OAc),, THF; ii, KBr; iii, NaBH,

Scheme 44
N-Aryl-piperidines (112) have been prepared as shown in Scheme 44,I2l and

bridged piperidines (115) have been formed by novel [a + 3-1 cycloaddition
reactions between cycloheptatriene (114) and the anions, e.g. (113), derived from
suitably structured imines (Scheme 45). '22
Tertiary amines, including N-alkyl-piperidines, are dealkylated by treatment
with phenylmethane- and benzene-thiolates in the presence of a palladium or
l ~ ~ reaction is very selective in that cleavage occurs in the
ruthenium ~ a f a 1 y s t .The
11' K. Warning and M. Mitzlaff, Tetrahedron Lett., 1979, 1565.
11* Y. Nomura, T. Bando, Y. Takeuchi, and S. Tomoda, Tetrahedron Lett., 1979,3453.
'19 G . Stork, R. M. Jacobsen, and R. Levitz, Tetrahedron Lett., 1979, 771.
F. E. Scully, J. Org. Chem., 1980,45, 1515.
lZ1 J. Barluenga, C. Najera, and M. Yus, Synthesis, 1979, 896.
lZ2 D. J. Bower and M. E. H. Howden, J. Chem. SOC.,Perkin Trans. 1, 1980,672.
lt3 S.-I. Murahashi and T. Y. Yano, J. Chem. SOC.,Chem. Commun., 1979, 270.
order tertiary > secondary > primary. Benzeneselenol (PhSeH) is the reagent
of choice for the dealkylation of highly hindered tertiary amines such as 1,2,2,6,6-
pentamethylpiperidine.'24 With this reagent, preferential primary cleavage
occurs; thus the pentamethylpiperidine is quantitatively converted into 2,2,6,6-
tetramethylpiperidine. Two groups have independently reported the formation
of ring-contracted products (117) and (118) when 2,2,6,6-tetramethyl-4-
piperidone (116) is treated with chloroform and strong alkali. The tri-
chloromethyl anion is thought to be the reactive species (Scheme 46). 12s*126
Reagents: i, CHCl,, 50"% NaOH, crown ether

Scheme 46
Quinoline, Isoquinoline, and their Benzo- and Hydro-derivatives.-The reaction

of anilines and aldehydes to give 2,3-disubstituted quinolines in yields of up to
82% is catalysed by a rhodium complex (Scheme 47).127
Reagents: i, R2CH,CH0, [Rh(norbornadiene)CI],, PhNO,, EtOH, at 180 "C

Scheme 47
The spiro-compound (119), formed by the photoreaction of ethyl diazoacetate

and diketen, is a versatile synthon for ring synthesis. Thus its reaction with aniline.
followed by acid-promoted cyclization of the resulting anilide (120), gives the
quinolone (121) (Scheme 48).12*
A new synthesis of 3-substituted quinolines, involving the reaction of the
Vilsmeier reagent with substituted acetanilides, is illustrated in Scheme 49.129
A number of quinoline syntheses have been based on o-vinylaniline deriva-
tives. Thus quinolines, e.g. (123), are formed when solutions of o-(vinyl)-
124 H. J. Reich and M. L. Cohen, J. Org. Chem., 1979, 44, 3148.
J. T. Lai and J. C. Westfahl, J. Org. Chern., 1980, 45, 1513.
H. Lind and T. Winkler, Tetrahedron Lett., 1980, 21, 119.
''' Y . Watanabe, M. Yamamoto, S. C. Shim, T.-A. Mitsudo, and Y . Takegami, Chem. Lett., 1979.
1025.
T. Kato, N. Katagiri, and R. Sato, J. Chem. SOC.Perkin Trans. 1, 1979, 525.
0. Meth-Cohn, S. Rhouati, and B. Tarnowski, Tetrahedron Lett., 1979, 4885.
70,Et /-'C02Et
cis- and trans-isomers (121) [86%]

Reagents: i, PhNH,; ii, H,SO,
Scheme 48
Reagents: i, 1.5 M-DMF in 7M-POC13, at 75 "C; ii, Zn, 90% AcOH

Scheme 49
Me
H (123) [69%]
(122)
Scheme 50
thioanilides, e.g. (122), in acetonitrile are irradiated with Pyrex-filtered light

(Scheme 5O).l3O
o- (Viny1)acetanilides (125), obtained by the reaction of the complex (124)
between palladium acetate and acetanilide with alkenes, undergo acid-catalysed
cyclization to quinolines (126) (Scheme 5 1 ) , 1 3 ' and o- (bromoviny1)acetanilides
(127) are converted into 2-quinolones (128) via palladium-catalysed carbonyl-
ation (Scheme 52).13'
AcO
'
QJ1JMeqJ -
(124)
H
2 2
CH=CHR
NHCOMe
(125) R = CHO, C 0 2 M e ,
or COMe
ax
(126) X = H, OH, or Me
Reagents: i, RCH=CH,, Et,N

Scheme 51
NHCOMe RD H o
R
(127)
Reagents: i, CO, [Pd(OAc),], PPh3, Bu",N, HMPT
Scheme 52
P. de Mayo, L. V. Sydnes, and G. Wenska, J. Org. Chem., 1980,45, 1549.
13' H. Horino and N. Inoue, Tetrahedron Lett., 1979, 2403.
M. Mori, K. Chiba, N. Ohta, and Y. Ban, Heterocycles, 1979,13, 329.
Rearrangement occurs during the palladium-catalysed cyclization of a-
substituted-N-acryloyl-o-bromo-anilines(129), and 4-substituted, e.g. (130),
rather than 3-substituted quinolones are obtained (Scheme 53).133
Substituted 4-aminoquinolines, e.g. (131)and (133), result from the cyclization
of the substituted o-cyano-aniline (132); the product that is formed depends on
the choice of cyclizing reagent (Scheme 54).134
Reagents: i, Pd(OAc),, P(o-Tol),, Et,N, at 100 "C

Scheme 53
(131) [63%] H (133) [75':6]

(132)
Reagents: i, AICI,; ii, NaOMe
Scheme 54
4-Dimethylamino-2,3-polymethylenequinolines (134) are obtained by heating
the appropriate cycloalkanone with methyl anthranilate in hexamethylphos-
phoric triamide (HMPT) in the presence of a catalytic amount of polyphosphoric
acid. At lower temperatures, quinolinones are isolated; o-amino-NN-dimethyl-
benzamide, rather than an anil, is thought to be the intermediate (Scheme 55).135
(134) n = 4 , 5 , 6, or 8 [13-65%]
Scheme 55
The reaction of isatoic anhydrides with the anions derived from active-
methylene compounds has led to the isolation of a considerable number and
~ ~ have been two reports of the preparation of
variety of q u i n 0 1 0 n e s . ~There
cycloalkano-pyridines, e.g. (137), by thermolysis of cycloalkanone oxime O-ally1
ethers, e.g. (135); an intermediate nitrone (136) is formed (Scheme 56).137*138
Thermolysis of pyrimidine betaines of type (138) yields quinolones (139) uifil
keten intermediates (Scheme 57),139and the vapour-phase reaction of indole and.
133 M. 0.Terpko and R. F. Heck, J. Am. Chem. Soc., 1979,101,5281.
134 H. Schaefer, K. Sattler, and K. Gewald, J. Prukt. Chem., 1979, 321, 695.
13' 0. Osbirk and E. B. Pedersen, Actu. Chem. Scund., Ser. B , 1979,33, 313.
136 G. M. Coppola and G. E. Hardtmann, J. Heterocycl. Chem., 1979,16, 1605.
13' H. hie, I. Katayama, Y. Mizuno, J. Koyama, and Y. Suzuta, Heterocycles, 1979, 12, 771.
13' T. Kusumi, K. Yoneda, and H. Kakisawa, Synthesis, 1979, 221.
139 T. Kappe and W. Lube, Chem. Ber., 1979,112,3424.
(138) R = Et, CH2Ph, or Ph
(139)
Scheme 57
chloroform at a high temperature (550 "C)affords 3-chloroquinoline as the main
product (see also p. 254).14('
Reduction of the succinimide (140)with di-isobutylaluminium hydride gives a
mixture of diastereoisomers (14l),treatment of which (with formic acid) gives
the cis-decalin (142)stereospecifically (Scheme 58).141
H
0
(fb H 0
$ H
The reactions between 2-alkyl-quinolines and dimethyl acetylenedicarboxy-

late have been further investigated, and a mechanism for the formation of the
cyclobutapyrroloquinoline (143)from 2-methylquinoline has been proposed. 14*
The reaction of the 2-(benzylsulphonyl)quinoline (144)with sodium methoxide
unexpectedly gives the 2-methoxylated benzyl ketone (145)via the intermediate
formation of a thiophen S S - d i 0 ~ i d e . l ~ ~
ortho-Lithiation of 2-,3-,5-,6-, and 7-fluoroquinolines has been achieved by
the reaction at a low temperature (-60°C) with lithium di-isopropylamide in
THF, this system obviating the problem of addition reactions.144 A variety of
R. E. Busby, S. M. Hussain, M. Iqbal, M. A. Khan, J. Parrick, and C. J. Granville Shaw, J. Chem.,
SOC.,Perkin Trans. 1, 1979, 2782.
D. J. Hart, J. A m . Chem. Soc., 1980, 102, 397.
R. M. Acheson and G. Proctor, J. Chem. SOC.,Perkin Trans. I, 1979,2171.
143 E. A. Harrison and K. C. Rice, J. Org. Chem., 1979, 44,2977.
144 F. Marsais, E. Bouley, and G. Queguiner, J. Organomet. Chem., 1979, 171, 273.
Me0,C C0,Me
(144)R' = S02CH2Ph,R2 = C02Me
M e 0 , C(143)
%02Me (145) R ' = OMe, R2 = COCH2Ph
8-substituted quinolines has been prepared from 8-lithio-quinolines; the lithio-

derivative is obtained from 8-bromoquinoline and s-butyl-lithium in THF at
-78 0C.145 Ring-contraction occurs when methylation of 3-hydroxy-4-
nitroquinoline is attempted; thus, on treatment with dimethyl sulphate and
sodium hydroxide, the principal product formed is 3-nitro-1 -methylindole.146
Irradiation of 4-allyloxy-2-quinolone ( 146) results in the regio- and stereo-
selective formation (in 85% yield) of the tetracyclic compound (147); treatment
of the latter with sodium methoxide gives a quantitative yield of the 2-(hydroxy-
methyl)cyclobuta[c]quinolone (148) (Scheme 59).'"
+
hu
I& 0-
NaOMe
__.+ flo H
H
(147) (148)
Scheme 59
Qf
J L 0
Reagents: i , MeCOCH,CH&MeEt, I-, KOH; ii, PhNH,, 180 "C

H
Scheme 60
An elegant new synthesis of polycyclic heteroaromatic compounds via

quinone-methide intermediates is illustrated in Scheme 60. The required
quinone-methides have also been generated from hydroxy-pyridones and
-coumarins, and these have been allowed to react with a wide selection of
aromatic a m i n e ~ . ' ~ '
145 J. W. Suggs and G. D. N. Pearson, J. Org. Chem., 1980,45, 1514.
146
K. M. Dyumaev and E. P. Popova, Chem. Heterocycl. Compd. (Engl. Transl.), 1979, 15, 418.
147
C. Kaneko, T. Naito, and M. Somei, J. Chem. SOC.,Chem. Commun., 1979,804.
'41 J. L. Asherson and D. W. Young, J. Chem. SOC.,Perkin Trans. 1, 1980, 512.
On treatment of both quinoline and pyridine N-oxides with bromine and
thallium(Ir1) acetate, y-bromo-derivatives are formed; pyridine N-oxides are the
less reactive The reaction of 8-methoxyquinoline N-oxide with
acetic anhydride and methanol yields 84% of 2,8-dimethoxyquinoline. Similarly,
the reaction of the 6-methoxy-N-oxide and ethanol and acetic anhydride gives
2-ethoxy-6-methoxyquinoline,but, under the same conditions, the 7-methoxy-
N-oxide is ~nchanged.'~' The Reissert compounds (149) derived from
substituted quinolines, on treatment with thallium(Ir1) nitrate and trimethyl
orthoformate, undergo either smooth ring-contraction or oxidative debenzoyl-
ation, depending on the substitution pattern in the aromatic ring (Scheme 61).151
[R'= H I
[Rz=oM$
CN CN
COPh COPh
R
H
R 2\'W C N
Scheme 61
1-Benzyl-3-carboxamido- 1,4-dihydroquinoline,which is an acid-stable model

of NADH, reduces benzoylformic acid (PhCOC02H)in the p H region where the
carboxyl group is undissociated. 152
A general synthesis of c -fused pyridines under neutral conditions involves the
thermolysis of vinyl azides, prepared from aromatic aldehydes that bear an ortho
methyl group and ethyl azidoacetate. Thus thermolysis of the vinyl azide (151)
from mesitaldehyde (150) gives the isoquinoline (152) in 45-50% yield (Scheme
62).153
(150) (151) (152)

Reagents: i, N,CH2C02Et, NaOEt, HOEt, at 0 "C; ii, boiling PhMe
Scheme 62
Intramolecular cyclization of the unsaturated amide (153) is effected by

treatment with palladium(11) acetate and triphenylphosphine; reduction of the
resulting mixture of geometrically isomeric esters (154) gives the isoquinolone
(155) (Scheme 63).lS4
The base-catalysed reaction of the nitrophthalimide (156) with methyl
isocyanoacetate gives the oxazole (157), which is converted into the isoquinolone
'41 H. Saito and M. Hamana, Heterocycles, 1979, 12, 475.
lSo M. J. Dimsdale, J. Heterocycl. Chem., 1979, 16, 1209.
lS1 E. C. Taylor, 1. J. Turchi, and A. McKillop, Heterocycles, 1978,11, 481.
lS2 S. Shinkai, H. Hamada, Y . Kusano, and 0. Manabe, Tetrahedron Lett., 1979, 3511.
lS3 T. L. Gilchrist, C. W. Rees and J. A. R. Rodrigues, J. Chem. Soc., Chem. Commun., 1979,627.
154 M. Mori and Y. Ban, Tetrahedron Lett., 1979, 1133.
24 6 Heteroc yc 1ic Chemistry
fCo2Me
--*
a\ : H ,Ph
(153) (154)
Scheme 63
0 0-N
(156) (157)
Reagents: i, CNCH,CO,Me, DBU; ii, CH,N,; iii, MeOH-HCI
Scheme 64
(158) by sequential treatment with diazomethane and methanolic hydrogen

chloride (Scheme 64).lsS
1,3-Dimethylisoquinolines(161) are obtained in a one-pot reaction by treat-
ment of the oximes (159) with phosphorus pentachloride. Beckmann rearrange-
ment is followed by cyclization of the resulting imidoyl chloride (160) with
phosphorus pentoxide (Scheme 65).156
The 4-(methoxycarbonylamino)isoquinolone (163) is prepared in 84% yield
by cyclization of compound (162) with methanesulphonic acid. The starting
material is obtained from benzylamine, glyoxylic acid (HCOC02H),and methyl
carbamate (H2NC02Me)(Scheme 66).'*' Aluminium-chloride-promoted cyc-
lization of the benzylaminopropyl bromide (164) gives 64% of the isoquinoline
(165) and 14% of the benzazepine (166) (Scheme 67).'58
R R P
Scheme 65
r-.-qyR,CH
(162) R = NHC02Me
\
R
0
(163)
Scheme 66
lS5 K. Nunarni, M. Suzuki, K. Matsurnoto, M. Miyoshi, and N. Yoneda, Chem. Pharm. Bull., 1979,27,
1373;K.Nunami, M.Suzuki, and N. Yoneda, J. Org. Chem., 1979,44,1887.
W.Zielinski, Synthesis, 1980,70.
lS7 D.Ben-Ishai, N. Peled, and I. Sataty, Tetrahedron Lett., 1980,21,569.
C.D.Perchonock and J. A. Finkelstein, J. Org. Chem., 1980, 45, 2000.
Tetrahydroisoquinolines (168) are obtained stereoselectively by cyclization of

the lactams (167), induced by polyphosphoric acid (Scheme 68).ls9An ingenious,
stereoselective approach to the synthesis of reduced isoquinolines (169) is
illustrated in Scheme 69. This involves Diels-Alder addition, Wittig alkenylation,
and Cope rearrangement reactions.'60
Tetrahydroisoquinolines have been prepared from dibenzo[a,d]cyclo-octenes
by a number of interesting transannular reactions. Noteworthy is the formation
of the 6,12-imine (171) from the amine (170), since this requires the addition of
the amine to an apparently inactivated double-bond; a radical mechanism has
been postulated (Scheme 70).16' I1
Me0,CN Me0,CN
iii
I
Me0,C
w
(169)
Reagents: i, H,C=CHCHO; ii, Et,N; iii, Ph,P=CHCO,Me; iv, heat
Scheme 69
lS9 B. E. Maryanoff and D. F. McComsey, Tetrahedron Lett., 1979, 3797.
P. A. Wender, J. M. Schaus, and D. C. Torney, Tetrahedron Lett., 1979, 2485.
16' B. E. Evans, P. S. Anderson, M. E. Christy, C. D. Colton, D. C. Remy, K. E. Rittle, and E. L.
Englehardt, J. Org. Chem., 1979, 44, 3127; M. E. Christy, P. S. Anderson, S. F. Eritcher, C. D.
Colton, B. E. Evans, D. C. Remy, and E. L. Englehardt, ibid.,p. 31 17.
NHMe
&T-y&yJ CH2 Me
(170) (171)
Reagents: i, BuLi, THF, at r.t.
Scheme 70
Treatment of isoquinoline with sulphuryl chloride and potassium cyanide gives
4-chloro-1-cyanoisoquinolineand l-carbamoyl-3-cyanoisoquinoline,the rela-
tive yields of the two products depending upon the proportion of reagents.16’
The Reissert compound from 4-methylisoquinoline gives the bromohydrin (172),
and this, on treatment with aqueous sodium hydroxide, affords the benzoylimino-
-e0
compound (173). Hydrolysis of the latter with dilute hydrochloric acid yields
4-methylisocoumarin (174) (Scheme 71).163
Br Me
@OH_@$ NCOPh
CN NCOPh 0
(172) (173) (174)
Scheme 71
1-Amino-naphthalenes (176) are obtained by treatment of isoquinolinium
salts (175) with amines (Scheme 72),164 and 4-(methylaminomethy1)indole
is formed when 2-methyl-5-nitroisoquinolinium iodide is reduced with
titanium(II1) chloride.165
Photolysis of 1-substituted isoquinoline N-ethoxycarbonylimides (177) affords
1H-1,3-benzodiazepines (178), but irradiation of the 1-unsubstituted isoquino-
line imide gives only 1-(ethoxycarbonylamino)isoquinoline (Scheme 73).166In
this context, it is of interest that irradiation of 7-methylthieno[2,3-c]pyridine
N-imides (179) yields a mixture of 1,3- and 2,3-diazepines (180) and (181)
(Scheme 74).16’
(175) (176) E = C02Et

Reagents: i, EtNH,, at 150°C, for 7 h
Scheme 73
Scheme 1 2
16’ G.W.Kirby, S. L. Tan, and B. C. Uff, J. Chem. SOC.,Perkin Trans. 1, 1979, 270.
163 G. W. Kirby, J. W. M. Mackinnon, S. Elliot, and B. C. Uff, J. Chem. SOC.,Perkin Trans. 1, 1979,
1298.
164 A. N. Kost, L. G. Yudin, R. S. Sagitullin, V. I. Terenin, and A. A. Ivkina, Khim. Geterotsikl. Soedin.,
1979, 1386.
165 M. Somei, F. Yamada, and C. Kaneko, Chem. Lett., 1979,943.
166
T. Tsuchiya, M. Enkaku, J. Kurita, and H. Sawanishi, J. Chem. SOC.,Chem. Commun., 1979,534.
167
T. Tsuchiya, M. Enkaku, and H. Sawanishi, Heterocycles, 1979, 12, 1471.
(179) R = Et or CH2Ph (180) [7-lO%] (181) [30-55%]

Scheme 74
5,6-Dihydroisoquinolinesisomerize to 1,2-dihydroisoquinolineson treatment

with potassium amide.16’
Gas-phase pyrolysis of the (hydroxymethy1)aniline (182) yields acridine (183)
in 64% yield, and similar treatment of N-phenylanthranilic acid (184) gives 87%
of acridone (185) (Scheme 75).16’
0
Scheme 75
The reaction of 2,2’,4,4’-tetranitrobenzophenones,e.g. (186), with aromatic
amines affords 10-aryl-acridones, e.g. (187), (Scheme 76),17” and irradiation
of 9-cyanoacridine 10-oxide (188) produces the unstable oxazepine (189)
(Scheme 77).171
0
n- NO, II
0
The iminyls (19l ) , generated by oxidation of imino-oxyacetic acid derivatives

of type (190) with persulphate, undergo intramolecular cyclization to 6-
substituted phenanthridines (192) in yields of up to 78% (Scheme 78); N-
methoxybiaryl-2-carboxamides undergo analogous cyclization to phenan-
thridones, and triarylvinyliminyls similarly yield 2,3,4-triaryl-q~inolines.”~
16’ T. R. Kasturi and L. Krishnan, Tetrahedron Lett., 1980, 21, 865.
16’ Y. Mao and V. Boekelheide, J. Org. Chem., 1980, 45, 1547.
‘’O J. H. Gorvin and D. P. Whalley, J. Chem. SOC., Perkin Trans. 1, 1979, 1364.
S. Yamada and C. Kaneko, Tetrahedron, 1979,35, 1273.
17’ A. R. Forrester, M. Gill, J. S. Sodd, and R. H. Thomson, J. Chem. SOC., Perkin Trans. 1, 1979,612;
A. R. Forrester, E. M. Johansson, and R. H. Thomson, ibid., p. 1112.
D R
(191) (192)
Scheme 78
Spectroscopic evidence has been obtained for the formation of an oxaziridine

intermediate (194) in the photochemical conversion of 6-cyanophenanthridine
5-oxide (193) into 5-ethoxyphenanthridone (195) (Scheme 79).173
Angular, e.g. (197), rather than linear isoquinolines are formed by Bischler-
Napieralski cyclization of (2-naphthylethy1)amides of type (196) (Scheme
EtOH
(193) (194) (195)

Scheme 79
(196)
Reagents: i, PPA, P , 0 5 , at 170 "C
Scheme 80
4 Diazines and their Reduced and Fused Derivatives

1,2-Diazines.-Diazomethane adds to cyclopropenyl phosphonates (198), giving
the cyclo-adducts (199) in quantitative yields; these are readily transformed into
the 1,4-dihydropyridazines (200) in yields of 90-94% (Scheme 81).175
Hydrogenolysis of the readily available 2-(ary1azo)furanones (201), followed
by ring-closure of the resultant hydrazones (202), affords 1-aryI-pyridazin-4-
N>:; R' 5 5 R 3
HN," PO(OMe),
PO(OMe!,
(198) (199) (200)
Reagents: i, CH,N,, Et,O, at 0 " C ;ii, OH-
Scheme 81
173 K. Tokumura, M. Itoh, and C . Kaneko, Tetrahedron Lett., 1979, 2027.
174 D. Beaumont and R. D. Waigh, J. Chem. Res. (S), 1979, 332.
17' R. Regitz, W. Welter, and A. Hartman, Chem. Ber., 1979, 112, 2509.
Six-Mem bered Rings: Systems containing nitrogen 25 1
+
N
(201) (202) Ar
Reagents: i, H,, Pd/C, EtOH, at r.t.; ii, HOAc, heat for 10 min (203)
Scheme 82
ones (203) in good yields (Scheme 82)-176In a related reaction, betaines (205)
are obtained in yields of up to 93% by the action of aryl-hydrazines on the
2 -ace toxy -f uranones (204) (Scheme 83). 77
Several reports exist in the literature upon the formation of pyridazine deriva-
tives by the [4 + 2lcycloaddition of azo-alkenes with alkenes; one of these has
been shown to be incorrect, the isomeric N-amino-pyrroles being the products
formed from enamines, as exemplified in Scheme 84.178
(205)
Scheme 83
C0,Me
Reagents: i, O N 3
Scheme 84
An alternative cycloaddition route to tetrahydropyridazines, e.g. (207), is
furnished by the reaction of the now readily prepared arene diazocyanides (206)
with dienes; yields are fair to quantitative (Scheme 85).17’
The utility of a-dicarbonylmonohydrazones ArCOC(NNH2)R (R = H or Ph)
in pyridazine synthesis has been extended to the formation of 3-amino-4-cyano-
pyridazines (208) by reaction with malononitrile.180Oxidative ring-enlargement
(206) X = C1, NOz, or OMe (207)

Scheme 85
176 C. Venture110 and R. D’Aloiso, Synthesis, 1979, 790.
177 S. Gelin, J. Org. Chem., 1979,114, 3053.
17’ A. G. Schultz, W. K. Hagmann, and M. Shen, Tetrahedron Lett., 1979, 2965.
179 M. F. Ahern and G. W. Gokel, J. Chem. SOC., Chem. Commun., 1979, 1019.
K. Gewald and J. Oelsner, J. Prukt. Chem., 1979, 321,71.
of 2-alkyl- 1-aminopyrrolidines (209) occurs to give 3-alkyl- 1,4,5,6-tetrahydro-
pyridazines (210). The reaction is performed in methanol-chloroform in the
presence of silica gel and is thought to proceed uia a nitrene that is formed by
oxidation of the amino-function by chloroform at the silica surface.'81
(208) (209) (210)

Details of studies on the 13C n.m.r. spectra of substituted pyridazines,
pyrimidines, and pyrazines have appeared. Calculated (MIND0/2) charge
densities have been correlated with substituent-induced 13C chemical shifts of
these diazines.ls2
Thermal rearrangement of, e.g., perfluor0-4,5-di-isopropylpyridazine(21 1)to
the corresponding pyrimidines and pyrazines (212) and (213) appears to be
sensitized by the presence of its di-s-butyl analogue (214). Thus heating (211)in
a sealed tube at 300°C results in 8% conversion, whereas 90% conversion is
obtained in the presence of (214). Photochemical sensitization is well known; this
is the first reported case of an analogous thermal process.183
Radical acylation of 4-(ethoxycarbonyl)pyridazine, followed by removal of the

ester group (by hydrolysis and decarboxylation) gives reasonable overall yields
of 5-acyl-pyridazines; this is a useful general method, as pyridazine cannot be
acylated under Friedel-Crafts conditions, and radical acylation has been reported
to give disubstitution products. 184 Pyridazine N-oxide reacts with alkyl Grignard
reagents to afford 1,4-dialkyl-butadienes in rather low yields; this is in marked
contrast to the known formation of 1-aryl-but-l-en-3-ynes from aryl Grignard
reagents.la5
An interesting route to cyclopropa[c]cinnolines is exemplified in Scheme 86;
the 1,3-dipole generated from (215) is reacting in its carbenoid mode. Thermal
treatment of the product (216; R' = Me, R2 = H) results in rapid formation of
an equilibrium mixture of (216; R' = Me, R2 = H) and its stereoisomer (216;
R' = H, R2 = Me) and in slow conversion into the benzodiazepine (217);
both processes presumably occur via electrocyclic ring-opening to (218), with
ring-closure being faster than the 1,5-shift of hydrogen.'86"
la' N. Viswanathan and A. R. Sidhaye, Tetrahedron Lett., 1979, 5025.
lS2 T. Tsujimoto, C. Kobayashi, T. Nomura, M. Iifura, and Y. Sasaki, Chem. Pharm. Bull., 1979, 27,
2105.
R. D. Chambers and C. R. Sargent, J. Chem. Soc., Chem. Commun., 1979,446.
lS4 G. Heinisch and I . Kirchner, Monatsh. Chem., 1979,110, 365.
L. Crombie, N. A. Kerton, and G. Pattenden, J. Chem. SOC., Chem. Commun., 1979, 2136.
lS6 ( a ) A. Padwa and S. Nahm, J. Org. Chern., 1979, 44, 4746; ( b ) Y. Nishizawa, T. Miyashi, and T.
Mukai, J. Am. Chem. SOC.,1980,102, 1176.
E =C02Me
Scheme 86
A similar intramolecular [l,l]cycloaddition of a 1,3-dipole is observed in the

formation of (220) (86%) upon treatment of the diazoalkane precursor (219)
with base (NaH); other examples of this reaction are described, and in one case
the intermediate diazoalkane was isolated and separately transformed into a
homopyrazole.186b
1,3-Diazines.-The utility of N-cyano-amidine derivatives of malonic acid in

pyrimidine synthesis has been extended by the use of the ester (221). The nitrile
function can be selectively attacked by water or secondary amines and the
products then cyclized to pyrimidine derivatives (Scheme 87).lS7
I
+
0 OEtCN 0
Reagents: i, H', NucH (Nuc = OH or NR',); ii, heat

Scheme 87
Tetrachloropyrimidine is formed in quantitative yield by the cyclization

(with FeCl,, at 200 "C) of perchloro-1 -cyano-3-azabutadiene
(Cl,C=N-CCl=CClCN), itself formed by successive treatment of N- (p-
cyanoethy1)formamide with phosphorus pentachloride and chlorine.188
p-Iminoyl-enamines (222), prepared by the reaction of the appropriate anils
with nitriles, condense with ethyl chloroformate and carbon disulphide to give
excellent yields of 2-0x0- and 2-thioxo-pyrimidines (223; X = 0 or S).lSga
Aldehydes, acetals, and ketals (but not ketones) also react with these enamines
(222) to give 1,2-dihydropyrirnidines (224) (70-93°/~).189b In similar fashion,
malondiamidines condense with a large variety of aromatic aldehydes to give
2-aryl-5-arylmethyl-4,6-diaminopyrimidines.
'I3' J. M. McCall, B. V. Kamdar, and D. Kloosterman, Synthesis, 1980, 123.
'I3' G. Beck, F. Doering, and H. Holtschmidt, Swiss P. 613 196 (Chern. Abstr., 1980, 92, 41 977).
(a)J. Barluenga, M. Tomis, V. Rubio, and V. Gotor, J. Chern. SOC.,Chern. Cornmun., 1979, 675;
( b ) J. Barluenga, M. Tomas, S . Fustero, and V. Gotor, Synthesis, 1979, 346.
H. Meyer, Liehigs Ann. Chem., 1979, 1291.
R4 0 0
I R4 II II
(225)
C0,Et
(226)
Good yields of 2-chloro-pyrimidines are obtained by passing a mixture of
chloroform and a C-methyl-pyrazole, or pyrazole itself, through a continuous
flow reactor at 555 "C; thus 3-methylpyrazole affords 2-chloro-4-methylpyri-
midine (77%). 2-Chloroquinazoline may likewise be obtained from benzo[c]-
pyrazole (68%), but mono-azoles do not generally give synthetically useful yields
of the corresponding mono-azines, because mixtures are obtained.'"
Heating diphenylcyclopropenone (DPP) with aryl amidoximes
ArC(NH2)NOH gives pyrimidin-4-ones (225); this usefully supplements the
previously reported reactions of DPP with amidines, which give dihydro-
pyrimidin-4-0nes.'~~ The previously mentioned p-lactone (119) (see p. 240),
which is an internally protected 1,3-dicarbonyl compound, reacts with
acetamidine to give the pyrimidin-4-one (226)."*
A novel route to pyrimidines bearing a vinylic, acetylenic, or aromatic group
at position 5 is depicted in Scheme 88; evidence is presented in support of the
thesis that the reaction proceeds by way of a di-?r-methane rearrangement.
Overall yields are limited (<35%).lg3
R
Reagents: i, RLi; ii, H,O; iii, hv, acetone; iv, KMnO,

Scheme 88
Chichibabin amination of 4-phenylpyrimidine gives both the 2-amino- and

6-amino-derivatives, in 60 and 15% yields, respectively; 15N-labelling showed
that, in contrast to the 6-amino-derivative, the 2-amino-compound is formed by
an ANRORC
Further work has appeared on the palladium(I1)-catalysed alkenylation of
halogeno-pyrimidines (see also p. 230). The scope of the reaction had appeared
to be neatly delineated in that 5-iodo- or 5-bromo-pyrimidines undergo the
reaction whereas 2- or 4-iodopyrimidines do not; it has now been discovered
that, if the 4-iodopyrimidine possesses a substituent in the 5-position, e.g. (227;
Z = I, Br, C1, or Et), then alkenylation will occur (Scheme 89). Particularly
noteworthy is the selective reaction at position 4 of the 4,5-di-iodo-compound
(227; z = 1 j . 1 ~ ~
R. E. Busby, J. Parrick, S. Mumtaz, H. Rizvi, and C . J. Granville Shaw, J. Chem. Soc., Perkin Trans.
1, 1979, 2786.
M. Takahashi and S. Watanabe, Chem. Lett., 1979, 1213.
ly3 R. E. van der Stoel and H. C. van der Plas, J. Chem. SOC.,Perkin Trans. 1, 1979, 2393.
194 K. Breuker and H. C. van der Plas, J. Org. Chem., 1979,44,4677.
Iy5 K. Edo, T. Sakamoto, and H. Yamanaka, Heterocycles, 1979, 12,3 8 3 .
i Z
N N
(227) 0 0 0 0
Reagents: i, Pd(OAc),, Ph,P, Et,N, PhCH=CH2, Me

XMe Me
XMe
at 130°C Reagents: i, LDA, THF, at -78 "C; ii, RX
Scheme 89 Scheme 90
Uridines have been converted into 6-alkyl-uridines as depicted in Scheme 90;

the hydroxyl group is thought to govern the initial site-specific 1ithiati0n.l~~
The indolo-uracil (230) is obtained upon heating the 6-( p-toly1hydrazino)-
uracil (228) in formic acid. Under milder conditions the 'Fischer intermediate'
(229) can be isolated in 35% yield, and can be separately converted into the
indolo-uracil (Scheme 91).19'
Reagents: i, 1M-HCI, heat for 1 h; ii, NNdimethylaniline, heat for 2 h

Scheme 91
The recently developed dealkylation of phenol ethers with trimethylsilyl iodide
has been shown to work well for 00'-dialkyl-ura~ils,'~~ A number of ring
transformations of uracils have been reported. The [2 + 2]cyclo-adducts (232)
can be transformed into pyridones (233) by treatment with base; overall yields
of pyridines from the starting uracils (231) can be quite reasonable. The reaction
is thought to proceed via electrocyclic ring-opening of the dianion of (232)
(Scheme 92).199
Reagents: i, R2CrCR3, h v ; ii, KOBu' ( 2 equivalents), HOBu', heat

Scheme 92
196 H. Tanako, I. Nasu, and T. Miyasaka, Tetrahedron Lett., 1979,4755.

197 G. E. Wright and J. Gambino, J. Heterocycl. Chem., 1979, 16, 401.
'91 R. B. Silverman, R. E. Radak, and N. P. Hacker, J. Org. Chem., 1979,44,4970.
199 R. N. Comber, J. S. Swenton, and A. J. Wexler, J. A m . Chem. SOC.,1979,101, 5411
Treatment of 5-substituted 1,3-dimethyluracils (234) with base and an
acetamide gives pyridine-2,6-diones (235);200"1,3-dimethyl-5-azauracil (236)
undergoes the same type of rearrangement, giving the 5-substituted uracils (237)
(Scheme 93).200h
0 (254 nm)
Me
(235) X = C R '
H (239)
(234) X = C R '
(236) X = N (237) X = N (238) [3 5-6 5 O/o ]
Reagents: i, R2CH2CONH2,NaOEt, HOEt Scheme 94
Scheme 93
Photolytic conversion of the alcoholates of 5-diazouracil(238) into the corres-

ponding imidazolecarboxylates (239) is very slow in neutral solution (ca. 10-
15% conversion after 20 h) but is complete in 4-5 h when performed in a
solution that is saturated with hydrogen chloride (Scheme 94).201Triazoles (241)
are formed by acid-catalysed rearrangement of the N-amino-barbituric acids
(240; X = 0 or S) (Scheme 95).202
1,3-Dimethylperhydropyrimidine exists as a mixture of ring and open-chain
tautomers in trifluoroacetic acid; other saturated heterocyclic systems have also
been studied (see p. 274).203
H R2
RCC0,H
d
H' H N A
X A,." R'
H [62-8 8 O h ]
(24 1) Reagents: i, Ph,P(SCN),, at -40"C, for 1 h;
(240) [2 1-8 3 Yo ] ii, at r.t., overnight
Scheme 95 Scheme 96
An improved procedure for the conversion of o-acyl-anilines into quinazoline-

2-thiones has appeared (Scheme 96);204 the use of triphenylphosphine
dithiocyanate (see also p. 274) is said to give better yields than older procedures
(e.g. NaSCN,HOAc).
Several reports have appeared upon the preparation of quinazolin-4-ones. The
most interesting consists of heating o-azidobenzamides (242; R = H or Me) in
aromatic aldehydes; yields are good and are unaffected by the nature of X (H,
OMe, or NOz). Benzoxazines can likewise be obtained from o-azidobenzoic acid
(seep. 275), and the mechanism is briefly discussed in that section (Scheme 97).20'
200
Hirota, Y. Kitada, S. Senda, M. J. Halat, K. A. Watanabe, and J. J . Fox, J. A m . Chem. SOC.,
( a ) K.
1979,101,4423; (6) W. K. Chung, C. K. Chu, K . A. Watanabe, and J. J. Fox, J. O r g . Chem., 1979,
44, 3982.
201
B. Stanovnik, M. TiSler, and E. VonEina, Heterocycles, 1979, 12, 761.
202
N. W. Jacobsen, B. L. McCarthy, and S. Smith, Aust. J. Chem., 1979, 32, 161.
203
J. B. Lambert and M. W. Majchrzak, J. A m . Chem. SOC.,1980,102,3589.
204
Y. Tarnura, T. Kawasaki, M. Tanio, and Y. Kita, Synthesis, 1980, 120.
205
G. S. Reddy and K . K. Reddy, Indian J. Chem., Sect. B, 1978,16, 1109.
0
Reagents: i, p-XC,H,CHO, at 110-1 15 "C

Scheme 97
A mild procedure for the high-yield cyclization of the o-cyano-anilides (243)

to quinazolinones (244) has been reported. The reaction does not proceed via
hydration of the nitrile group, because (245) does not cyclize under these
conditions (Scheme 98).'06
Heating isatoic anhydride (246) with Schiff bases in acetic acid gives good yields
of the dihydroquinazolin-4-ones (247); these are readily oxidized to the corres-
ponding quinazolin-4-ones (Scheme 99).'07 Irradiation of the sulphonamide
(248) in dichloromethane gives 2-phenylquinazolin-4-one in ca. 70% yield; the
mechanism of this reaction has been discussed.208
(243) (244) (245)

Reagents: i, 5 M-HCI, EtOAc, for 10 min, with vigorous stirring
Scheme 98
0
H H
Ph
(246) (247) Ts
Reagents: i, Ar'N=CHAr2, HOAc, at 100 "C (248)
Scheme 99
An elegant route to quinazoline-2,4-diones (25 1) starts, unusually, from
substituted uracils (249); other dienophiles (e.g. methyl vinyl ketone and
dimethyl fumarate) also cyclo-add to the dienolate anions (250) (Scheme
100).~0~
The previously unknown 5,6,7,8-tetrahydroquinazolineNN-dioxides (253;
R = H or Me) have been prepared from the hydroxylamino-oximes (252), using
a method that was known to work for the formation of pyrimidine dioxides
(Scheme 101).210
'06 G. A. Showell, Synth. Commun., 1980, 10, 241.
'07 V. Bhaskar and C. V. Ratnam, Indian J. Chem., Sect. B, 1979, 18,409.
'08 D. F. Eaton and B. E. Smart, J. Org. Chem., 1979, 44, 4435.
'
09 S. Senda, T. Asao, I. Suguyama, and K. Hirota, Tetrahedron Lett., 1980, 21, 531.
210 A . Ya. Tikhonov, L. B. Volodarsky, and 0. M. Sokhatskaya, Chem. Heterocycl. Compd. (Engl.
Transl.), 1979, 15, 1025.
O N
0
M e N 3 c o R
A
Me
Me
2 MeN
0 N
A
yR
-
CH,
Li
ii,iii
Me
(249) Me (25 1) X = H, Me, or OH
R = H, Me, or OEt (250) [49-8 3 % ]
Reagents: i, LDA, THF, at -70°C; ii, DMAD; iii, H’
Scheme 100
I
(252) 0-
(253)
Reagents: i, RCHO, EtOH; ii, active MnO,, dioxan, pyridine
Scheme 101
Cycloalkane-fused 1,4-dihydroquinazolines (255; n = 3 , 4 , or 5 ) are obtained
in superb yields by oxidation of the benzylamines (254) with mercuric oxide
(Scheme 102).211Equally facile formation of the thiazolo- and thiazino-[2,3-
blquinazolines (256; n = 2 or 3) occurs when methyl anthranilate is heated with
the appropriate w-chloro-isothiocyanate, Cl(CH,), NCS, under basic condi-
tions. 21 0
Reagents: i, HgO, EDTA

Scheme 102
Treatment of the N-cyano-imidates (257) with o-hydrazinobenzoic acid gives
triazolo[l,5-~]quinazolines(258). The hydrazine attacks the imidate carbon
initially, rather than the nitrile group; this contrasts with the preferential reaction
at the nitrile function of the similar N-cyano-amidines (221) by amines (see
p. 253) (Scheme 103).2’3
R
0
R = H, Me, or CH2CN (258)
Scheme 103
’” H. Morhle and J. Gerloff, Arch. Pharm. (Weinheim, Ger.), 1979, 312,839.
L. G. Payne, J . Przytycki, A. A. Patchett, and M. T. Wu, J. Heterocyci. Chem., 1979,16, 391.
’13 R. Heckendorn and T. Winkler, H e h . Chim. Acta, 1980, 63, 1.
1,4-Diazines.-Diaminomaleonitrile (DAMN) is known to condense straight-
forwardly with aromatic aldehydes to give the mono-imines (259); the reaction
with a second molecule of adehyde is interesting in that it is accompanied by
hydration of one of the cyano-groups. The resultant di-imines (260) cannot
always be isolated, as they readily cyclize to dihydropyrazines (261) (Scheme
104); overall yields of pyrazines (262) can be quite reasonable.214
-
NcIN=CArl
hit- NU-
H
H,NC
NCIN=CArl
N=CArZ
H
Ar
\
Reagents: i, A r 2 C H 0 , MeOH. Et,N, at CQ. 0 "C; ii, DMSO, at 80 "C;
HzNp
iii, MnO,, DMF, at 60°C 0
Scheme 104 (262)
Glyceraldehyde, CHOCH(OH)CH20H,similarly condenses with DAMN to

give a mono-imine which can be cyclized (with mercuric chloride), affording
2,3-dicyano-S-methyIpyrazine; other similar reactions are
2-Alkoxy-6-aminopyrazines(264) are obtained upon treatment of N-
nitrosobis(cyanomethy1)amine (263) with sodium alkoxides. The nitroso-group
is essential, which suggests that the reaction may proceed as outlined in Scheme
105.'16
A new synthesis of deoxyaspergillic acid (266) exemplifies the use of N-
phenyltriflamide (PhNHSO'CF,) in pyrazine synthesis (Scheme 106). The con-
NO
I
OR N
(263)
R = M e or Et (264) [45-50°/o]
Reagents: i, R O H , RONa, at r.t.
Scheme 105
(265)
(266)
A
Reagents: i, PhNHS02CF,, K,CO,, DMF, heat; ii, Me,CHCH2CH(NH2)CONH2, morpholine,
THF, heat
Scheme 106
214 Y. Ohtsuka, E. Tohma, S. Kojima, and N. Tomita, J. Org. Chem., 1979, 44,4871.
2
'
5 M. Sakaguchi, Y. Miyata, H. Ogura, K. Gonda, S. Koga, and T. Okamoto, Chem. Pharm. Bull.,
1979,27,1094.
216 S. K. Vohra, G. W. Harrington, D. E. Zacharais, and D . Swern, J. Org. Chem., 1979, 44, 1129.
densation of leucinamide with the imine (265) is selective in that only the
3,6-dialkyl-pyrazine (266) is formed.217
The imidoyl chloride (267) is a versatile reagent for the synthesis of
heterocycles; with DAMN and o-phenylenediamine it gives the pyrazinone (268)
and the quinoxalinone (269), respectively.218
H H
C1 XZEt
NMe iE<X:Me
N a N x : NM e
(267) (268) (269)
The previously unknown 1,2,3,6-tetrahydropyrazin-2-0nes(270) are easily

prepared by mixing 2,2-dimethyl-3-phenylazirine(271) with the methyl esters
of a - a m i n o - a ~ i d s Another
. ~ ~ ~ ~ example of the use of this azirine is seen in its
reaction with ammonia to give the amino-pyrazine (272) in 72% yield (Scheme
107).219b
Depending upon the conditions, mandelaldehyde (PhCHOHCHO) reacts with
1,2-diarninesto give either tetrahydropyrazines or tetrahydroimidazoles (see also
p. 275).220Treatmentof certain N-allyl-anilines (273) with mercuric acetate gives
trans-2,5-bis(bromomercuriomethyl)piperazines(274); the reaction appears to
be severely limited in scope in that ortho-substituents on the aryl group prohibit
the reaction and that substituents on the ally1 group similarly cause the reaction
to fail (Scheme 108).221
Ph 1
N
H
y N 1 O +
R
i
Ph
3 N
(271)
--+
ii phxN\r
H,N
N
H
(270) [33-75%]
Reagents: i, RCH(NH2)C02Me;ii, NH, (272)
ArNHCH,CH=CH, +
Scheme 107
i, ii Br HgH “i,-
(273) N ‘CH,HgBr
Ar
Reagents: i, Hg(OAc),, THF, at r.t.; ii, KBr, H,O (274)
Scheme 108
A much improved preparation of 2,6-diaminopyrazine involves the reduction

of 2,6-diazidopyrazine, itself obtained by treatment of 2,6-dichloropyrazine with
sodium azide. The reduction may be done catalytically (H2,Pd/C) in aqueous
ammoniacal glyme or with sodium borohydride; in either case, excellent yields
217 R. T. Bergeron and P. Hoffman, J. Org. Chem., 1980, 45, 163.
D. Bartholomew and I. T. Kay, Tetrahedron Lett., 1979, 2827.
”’ ( a ) A. V. Eremeev, R. S, El’kinson, and V. A. Imuns, Chem. Heterocycl. Compd. (Engl. Transl.),
1979, 15, 810; ( b ) A. V. Eremeev, R. S. El’kinson, M. Magi, and E. Liepins, Khim. Geterotsikl.
Soedin, 1979, 1352 (Chem. Abstr., 1980, 92, 94 346).
220 K. Therling and P. Tinapp, Arch. Pharm. (Weinheim, Ger.), 1979, 312, 1042.
22 1
J. Barluenga, C. Najera, and M. Yus, J. Heterocycl. Cliem., 1979, 16, 1017.
are obtained.222Another method for transforming chloro-pyrazines into amino-
pyrazines is to heat the substrate with benzamide in the presence of potassium
carbonate; yields range from 36 to 9 7 ' / 0 . ~ ~ ~
A similar method for making (methy1amino)pyrazines is to heat a chloro-
pyrazine with potassium hydroxide in N-methylformamide; yields are fair to
quantitative. In both of these latter reports, the applicability of the relevant
procedure to other heterocyclic systems has been investigated.224
Pyrolyses of 2-(alkylsulphonyl)pyrazines give mixtures of 2-alkyl-pyrazines
(0-5356) and pyrazine ( 0 4 9 % ) . As the starting materials are easy to prepare,
it had been hoped that this might be a useful synthetic route to alkyl-pyrazines,
but yields are really only adequate with primary alkyl groups; branching
decreases the yields dramatically.225
Two reports226have appeared on the formation of trisubstituted pyrazines by
base-catalysed condensation of 2,3-dihydro-5,6-disubstitutedpyrazines with
aldehydes and ketones; ap-unsaturated carbonyl compounds yield cyclopenta-
[blpyrazines (Scheme 109).
"'1
RZ\ CHR'R'
c RICN)
R2 \
11
[R'=R2=Me] '
N N
Me
Reagents: i, R3R4C0, NaOEt, HOEt, heat; ii, MeCOCH=CH,, NaOEt, HOEt
Scheme 109
(275)
Reagents: i, BuLi, hexane, at -70 "C; ii, BzCl, at -70 "C; iii, 0.5 M-HCl, at r.t.
Scheme 110
The methyl ester of L-alanine has been converted into, inter alia, its a-benzyl
analogue (276) by way of a dihydropyrazine (275). as depicted in Scheme 110.
The benzylation of (275) occurs with an enantiomeric excess of 93'/0.~~'
1,4-Ditosy1-1,2,3,4-tetrahydropyrazines (277) do not cyclo-add to dienes but
do form dioxins (278) with tetrachloro-o-benzoquinone.All efforts to eliminate
HX from (277), thus forming a 1,4-dihydropyrazine, were unsuccessful, this
being a testimony to the difficulty of forming unstable 87r systems.228
222
J. T. Shaw, C. E. Brotherton, R. W. Moon, M. D. Winland, M. D. Anderson, and K. S. Kyler, J.
Heterocycl. Chem., 1980, 17, 11.
223 T. Watanabe, E. Kikuchi, W. Tamura, Y. Akita, M. Tsutsui, and A. Ohta, Heterocycles, 1980, 14,
287.
224 T. Watanabe, Y. Tanaka, K. Sekuja, Y. Akita, and A. Ohta, Synthesis, 1980, 39.
225 T. Konakahara, K. Gokan, M. Iwama, and Y. Takagi, Heterocycles, 1979,12, 373.
226 H. Masuda, M. Tanaka, T. Akiyama, and T. Shibamoto, J. Agric. Food Chem., 1980, 28, 244; I.
Flament, P. Sonnay, and G. Ohloff, Bull. SOC.Chim. Belg., 1979,88, 941.
227 U. Schollkopf, W. Hartwig, and U. Groth, Angew. Chem., Int. Ed. Engl., 1979, 18, 863.
228 U. Eisner and A. J. Williams, J. Chem. SOC.,Chem. Commun., 1979, 606.
(277) (278)
X = H, C1, or SPh
The oxazolinones (279), readily available from a-amino-acids and hexa-
fluoroacetone, are excellent equivalents of a-keto-acids in that they give very
good yields of quinoxalinones (280) upon reaction with o-phenylenediamine
(Scheme 111).22y
NH, F,c 0
(279) H
(280)[66-92%]
Reagents: i, HOAc, EtOAc, at r.t.
Scheme 111
Thermolysis (at 600 " C ; mmHg) of the hydrazone (281) gives the two
isomeric quinoxalines (282) and (283) in a ratio of 7 : 13. The reaction is thought
to proceed via the iminyl radical (284), which can either cyclize by ortho-attack
to give (282) or can give the isomeric radical (285), by way of ipso-attack, as
shown; (285) can then cyclize to (283). An electrocyclic pathway to (282) does
not appear to compete with the radical one (Scheme l12).230
NHPh
/ t
Scheme 1112
Reduction of quinoxaline with potassium borohydride in acetic acid gives an

excellent yield of 1,4-diethyl-1,2,3,4-tetrahydroquinoxaline;phthalazine reacts
similarly, and other carboxylic acids can be
Two have appeared on the preparation of f-fused quinoxalines by
photocyclization of the appropriate arylvinyl-pyrazines; if performed in the
presence of air, yields can be excellent.
229 K. Burger and M. Eggersdorfer, Liebigs Ann. Chem., 1979, 1547.
230 H. McNab, J. Chem. SOC.,Chem. Commun., 1980,422.
231 J.-M. Cosmao, N. Collignon, and G. Qukquiner, J. Heterocycl. Chem., 1979, 16,973.
232 S. G. Shine and S. K. Lee, Synthesis, 1980, 116; A. Ohta, K. Hasegawa, K. Amano, C. Mori, A.
Ohsawa, K. Ikeda, and T. Watanabe, Chem. Pharm. Bull., 1979, 27, 2596.
The di-imine (287), obtained by base-catalysed ring-contraction of (286) (see
p. 27 1), condenses with o-phenylenediamine, giving the imidazolo-quinoxaline
(288) in 95% yield (Scheme 113).This is another example of the greater reactivity
of imines over carbonyls in the synthesis of 1,4-diazines, as the analogous
trioxoimidazole gives a spiro-compound with ~-phenylenediamine.*~~
0
Me Me Me
(286) (287) (288)
Reagents: i, morpholine, EtOH, heat; ii, o-phenylenediamine, AcOH
Scheme 113
Thermal decomposition of 2-azidophenazine in hydrocarbon solvents (e.g.

tetralin) gives 2-aminophenazine; photolysis in undegassed cyclohexane,
however, gives an excellent yield of the pyrrolo-quinoxaline (290)! A possible
mechanism, passing through the nitrile oxide (289), has been
5 Triazines and Tetrazines

Several reports have appeared on the preparation and chemistry of 1,2,3-
triazines. Heating trimethylsilyl azide with perchloro- or perbromo-cyclopropene
gives the corresponding triazine (291; X = C1 or Br). Nucleophilic substitution
of these trihalogeno-compounds occurs first at the 4- and 6-positions and only
finally at the 5-position; depending upon the conditions and the nucleophile,
mono-, di-, or tri-substitution products may be obtained (Scheme 114).235"
(291)
Reagents: i, NuH or Nu- (Nu= RO, R,N, or RS)
Scheme 114
A more direct route to dialkylamino-l,2,3-triazines(293) is the thermolysis of
the stabilized cyclopropenium azides (292) (Scheme 115).235b When all the
groups on the cyclopropenium salt are dialkylamino and they differ, the largest
ends up at the 5-position of the resultant triazine after thermolysis; the mechan-
233 E. C. Taylor and M. Inbasekaran, Heterocycles, 1978, 10, 45.
234 G. F. Bettinetti, E. Fasani, G. Minoli, and S. Pietra, Gazz. Chim. Ifaf.,1979, 109, 175.
235 R. Gompper and K . Schonafinger, Chem. Ber., 1979,112, (a)p. 1529; (b) p. 1514; (c) p. 1535.
Reagents: i, heat, in toluene

Scheme 115
ism has been discussed. Studies on the reactions of these 1,2,3-triazines with
electrophiles (e.g. H' and MeI) indicate that attack occurs at N-2 to give, e.g,,
(294), even in those cases when the substitution pattern might be thought to
favour an alternative
The isolation of a 45 o/' yield of trichloroacrylonitrile (296) upon thermolysis
(at 600 "C) of trichloro-1,2,4-triazine(295) may implicate an azete intermediate
(Scheme 1 16).236
CI
Cycloaddition to a 1,2,4-triazine, followed by extrusion of nitrogen from the

adduct, is a method of forming other aza-heterocycles; the potential of this type
of procedure is exemplified by the remarkably simple preparation of the 3,s-
methanoaza[lO]annulene (297), as depicted in Scheme 117.237
In the absence of air, o-aminophenylhydrazones of aldehydes (298) are in
equilibrium with tetrahydrobenzotriazines (299). Aeration of ethanolic solutions
of (299) results in successive oxidation to the dihydro- (300) and to the fully
aromatic species (301), as shown in Scheme 118.238
Reagents: i, benzocyclopropene, EtOAc, hexane, at 55 "C, for 26 h

Scheme 117
U
Scheme 118
236 R. D. Chambers, W. K . R. Musgrave, and D. E. Wood, J. Chem. SOC.,Perkin Trans. I , 1979, 1978.
23' M. L. Maddox, J . C. Martin, and J. M. Muchowski, Tetrahedron Lett., 1980, 21, 7.
238 R. Cerri, A. Boido, and F. Sparatore, J. Heterocycl. Chem., 1979, 16, 1005.
An interesting method of forming the triazine ring involves heating the azide
(302) in benzene, when (303) is obtained; which of the several plausible
mechanisms is operative is unknown (Scheme 119).239
A simple, high-yield, preparation of 1,3,5 -triazine by heating formamidinium
acetate with triethyl orthoformate has been Lewis-acid-catalysed
condensation of two molecules of a cyanogen halide with one of a
trihalogenomethyl compound, e.g. PhCC13, results in the formation of a 4,6-
dihalogeno-triazine, e.g. (304).241
C0,Et
C02Et
NI ~ P ; I H
HN-N
Ph
Scheme 119 (306)
The reaction of benzamidine with N-Chloromethylbenzimidoyl chloride (305)
gives the 1,4-dihydrotriazine (306).242Treatment of morpholine enamines (307)
with N-halogeno-benzamidines also gives dihydrotriazines (308), which are
readily oxidized to the corresponding 1,3,5-triazines (309); the mechanism of
triazine formation has been discussed (Scheme 120).243
(0) N
i
0 N
R I k R 2 A
(0)
R'&R2
N N N' N
R 1 i J
P h d I]Ph
R2 phll N )Ph N
(307) H (309)
(308)
Reagents: i, PhC(NH,)NX, CHCI,, pyridine; ii, chloranil, PhH, heat
Scheme 120
The alkyl adducts of triphenyl-1,3,5-triazine(310; X = N), upon heating to
200-300 "C, undergo a ring-opening-ring-closure process, giving the triphenyl-
pyrimidines (311; X = N). Similar treatment of the dihydropyrimidine (310;
X = CH, R = H) gives a somewhat poorer yield of triphenylpyridine (311;
X = CH, R = H); as yet, attempts to transform dihydropyridines into benzenes
by the same route have not been successful (Scheme 121).244
Hexahydrotriazines (312) react rapidly with acid chlorides to give the N -
(chloromethy1)carboxamides (3 3.3) in good yield. This is a considerable
239 L. Garanti and G. Zecchi, Tetrahedron Lett., 1980, 21, 559.
240 T. Maier, H. Brederick, and W. Kantlehner, Synthesis, 1979, 690.
241 K. Findeisen, Ger. Offen. 2 756 438 ((:hem. Abstr., 1979,91, 91 677).
"* H. Bohrne and H.-J. Drechsler, Arch. Pharm. (Weinheim, Ger.), 1979,312, 1011.
243 L. Citerio, D. Pocar, R. Stradi, and B. Givia, Tetrahedron, 1979, 35, 69.
244 L. S . Cook and B. J. Wakefield, Tetrahedim Lett., 1979, 1241.
Ph CH,R R’
/
X X NH -NH3 , X 3 R ( ) + R2COCl -+
R’NANR’ R2CON
\
Ph( //Ph Ph( / Ph N
N N R’
improvement on the old route of allowing a secondary amide to react with

formaldehyde, followed by chlorination (Scheme 122).245
The novel 1,2,3,6-tetrahydro-l,2,3,4-tetrazines (314) have been prepared by
the cycloaddition of azoalkenes with azodicarbonyl compounds; yields are good,
and the structure has, in one case, been confirmed by X-ray ~rystallography.’~~
The dihydrotetrazine (315) is converted into the aromatic system (316) (98%)
simply by heating (at 150-155 “C,for 30 min); the thermolability of the dihydro-
compound may be attributable to its 8 7
Cycloaddition of the tetrazine (317) to cyanamides R2NCN, followed by

extrusion of nitrogen, gives the 1,2,4-triazines (318) in good yield. A similar
reaction with N-(thionitroso)dimethylamine (Me2N-N=S) gives the triazole
(319), possibly by extrusion of sulphur from an initially formed t h i a t r i a ~ i n e . ’ ~ ~
(321)
Scheme 123
An interesting route to the pyrazolo[5,1-d][1,2,3,5]tetrazine (321) involves

addition of phenyl isocyanate to the diazo-diazole (320); this is formally a
. [2 + 8lcycloaddition (Scheme 123).249
6 Fused Systems containing One Five- and One

Six-Membered Ring (5,6)
3-Deazaguanine (322) has been prepared in 53% yield by the novel reductive
ring-closure reaction illustrated in Scheme 124.250
245 S. Gronowitz and Z. Lidert, Synthesis, 1979, 810.
246 S. Sommer and U. Schubert, Angew. Chem., Int. Ed. Engl., 1979, 18, 696.
247 S. Ito, A. Kakehi, T. Tanaka, K. Yoshida, and T. Matsuno, Bull. Chem. SOC.Jpn., 1979, 52, 483.
248 G . Seitz and W. Overheu, Chem.-Zrg., 1979, 103, 230.
249 G. Ege and K. Gilbert, Tetrahedron Lett., 1979, 4253.
P. C. Srivastava and R. K. Robins, J. Heterocycl. Chem., 1979, 16, 1063.
0
Reagents: i, Hz,Raney nickel

Scheme 124
The reaction of the triazole (323) with carbon disulphide does not yield the
expected triazolopyrimidine (325); the triazolothiazine (324) is formed instead
(Scheme 125).2s1Derivatives of pyrrolo[3,2-d]pyrimidine (327) are obtained, in
54--64'/0 yield, from pyrimidotriazines (326), the initial step being one of
cycloaddition of the alkyne to the nitrone function (Scheme 126).252
(325)
Scheme 125
Me
0-
MeN
OAN
9
Me
C0,Me
R
(326) (327)
R = H, Me, Et, or Ph
Reagents: i, MeO,CC_CCO,Me, PhMe, at 95 "C
Scheme 126
Pyrrolo[3,4-d]pyrimidines are formed by ring-closure of 4-dialkylamino-3-
benzoylpyrroles with urea, as illustrated by the formation of compound (329)
from (328) (Scheme 127).2s3Monomethylated derivatives of allopurinol, e.g.
(33l),are obtained via 4-(methylthio)pyrazolo[3,4-d]pyrimidine(330), as illus-
trated in Scheme 128; methylation of the anion of allopurinol itself yields 1,5-,
2,5-, and 2,7-dimethyl-derivati~es.~~~
H PJ--.
Me
N(CH,Ph),
'COPh
(3:8)
NH,CONH,
251
-PhCHO
__+
Scheme 127
HN
eI
Me
(329)
NH
Ph
C k
(330)
H
N %t
Reagents: i, MeI; ii, H,O

Scheme 128
A. Albert and A. Dunand, Angew. Chem., Int. Ed. Engl., 1980,19, 310.
0
Me
v
N N /
(331)
H
N
252 K. Senga, M. Ichiba, and S. Nishigaki, J. Org. Chem., 1979, 44, 3830.
253 G. Tarzia and G. Panzone, Gazz. Chim. Ital., 1978, 108, 591.
254 F. Bergmann, A. Frank, and Z. Neiman, J. Chem. SOC.,Perkin Trans. 1, 1979, 2795.
lin-Benzoallopurinol (332) has been prepared; it is a substrate (but not an
inhibitor) of xanthine oxidase.255alin-Benzoinosine, [in-benzoxanthosine, and
lin-benzoguanosine have also been synthesized.255h
The facile substitution of the halogen atom in 6-amino-l-benzyl-5-
bromouracil (333) by treatment with methylamine opens a new route to 7 -
methyl-xanthines, e.g. (334), and 7-methyluric
0
H N b , N H N 5 . r H L ~ z ~
kN / N
H
oAN NH*
CH,Ph
O N
H
(332) (333) (334)
A detailed study of the ‘H and 13C n.m.r. spectra of purine has been pub-
” reaction of purine with ”N-labelled potassium amide gives adenine
l i ~ h e d . ~The
that is labelled exclusively on the amino-nitrogen, indicating that no ring-opening
occurs.258 A new methylating agent, trimethylselenonium hydroxide
(Me3Se+OH-), is useful for methylating acidic NH, OH, and SH groups; it has,
for example, been shown to convert xanthine into caffeine in 85% yield.259An
enzymatic transarabinosylation has been carried out, using 2-chlorohypoxan-
thine and 1-P-D-arabinofuranosyluracil as substrates and Enterobacter aerugenes
as the facilitating micro-organism.2606-Lithio-9-(tetrahydropyran-2-yl)purine is
formed by the low-temperature (-130 “C) reaction of the 6-iodo-compound and
n-butyl-lithium. A t -78 “C, the 6-lithio-derivative rearranges within one hour to
the 8-lithio-compound.2616-(Alky1amino)adenosines are prepared by treatment
of adenosine with aldehydes or ketones and sodium cyanohydridoborate, in
acidic and 9-substituted adenines are simply de-aminated by irradi-
ation in THF in the presence of n-pentyl nitrite.263 2’,3’-O-Isopropylidene-
adenosine, -cytidine, and -guanosine react with formaldehyde in ethanolic sol-
ution to give the corresponding N-ethoxymethyl-derivatives R N H C H 2 0 E t ; this
is a reaction which is of interest in the context of the interaction of nucleic acids
with formaldehyde.264 9-Allyladenine 1-oxide (335; R = allyl) has been pre-
pared as shown in Scheme 129,265and derivatives of adenosine 1-oxide have
been shown to prevent N-3-5’ intramolecular cyclization during nucleophilic
substitution reactions that involve the sugar moiety. The parent nucleoside is
generated from the N’-oxide by using hexachlorodisilane or by hydrogenating
over Raney
”’ ( a ) R. H. Foster and N. J. Leonard, J. Org. Chem., 1979, 44, 4609; ( b ) G. E. Keyser and N. J.
Leonard, ibid., p. 2987.
2s6 W. Hutzenlaub and W. Pfleiderer, Liebigs Ann. Chem., 1979, 1847.
257 D. M. Cheng, L. S . Kan, P. 0. P. Ts’o, C. Geissner-Prettre, and B. Pullman, J. A m . Chem. Soc.,
1980,102,525.
2s8 N. J. Kos, H. C. van der Plas, and B. van Veldhuizen, J. Org. Chem., 1979,44, 3140.
2s9 Y. Yamauchi, K. Nakamura, and M. Kinoshita, Tetrahedron Lett., 1979, 1878.
260
H. Morisawa, T. Utagawa, T. Miyoshi, F. Yoshinaga, Y. Yamazaki, and K. Mitsugi, Tetrahedron
Lett., 1980, 21, 479.
’“ N. J. Leonard and J. D. Bryant, J. Org. Chem., 1979, 44,4612.
’” P. D. Sattsangi, J . R. Barrio, and N. J. Leonard, J. A m . Chem. SOC.,1980, 102, 770.
263 V. Nair and S. G. Richardson, Tetrahedron Lett., 1979, 1181.
264 P. K. Bridson, J. Jiricny, 0. Kemal, and C. B. Reese, J. Chem. Soc., Chem. Commun., 1980, 208.
26s T. Fujii, I. Inoue, T. Itaya, and T. Saito, Heterocycles, 1979, 12, 1543.
266 M. MacCoss, E. K. Ryu, R. S. White, and R. L. Last, J. Org. Chem., 1980, 45, 788.
(335; R = H)
Reagents: i, EtI; ii, H,C=CHCH,Br; iii, C,H,N, reflux
Scheme 129
A detailed study of the products of ozonolysis of caffeine, which is a common
component in waste water, has been made; the principal products are (336),
(337), and (338), in order of
MeN NMe
0 oANAo
Me 0 H
(336) (337) (338)
Imidazotriazinones (340), which are of interest as analogues of the naturally
occurring purine bases, are formed by an interesting rearrangement reaction of
dihydropyrimidines (339); an isocyanate intermediate has been postulated
(Scheme 130).268
Condensation of amidines with 4-amino- 1,2,3-triazole-5-carboxamides(341)
yields 2-substituted 8-azapurin-4-ones (342) and supplements a similar ring-
closure of the amino-amides with amides (Scheme 131).269
Irradiation of 1,3,7-trimethyl-8-azaxanthine(343) in a solution of diethyl-
amine in methyl cyanide yields the uracil derivative (344) (Scheme 132).270A
hypoxanthine analogue (345) has been prepared by ring-closure of the corres-
ponding imidazo-aminosulphonamide with triethyl o r t h ~ f o r m a t e . ’ ~ ~
0
N NH, N
(339) R = H or Me; (340) (34 1) (342)
X = NR2, OH, or SH
Reagents: i, Me,SiCI, C5H5N, at r.t.: ii, HMDS, heat Reagents: i, R2C(=NH)NH,
Scheme 130 Scheme 131
I .
(343) (344) H
Reagents: i, h v ( A = 254 nm), in MeCN and Et2NH (345)
Scheme 132
267 K. J. Kolonko, R. H. Shapiro, R. M. Barkley, and R. E. Sievers, J. Org. Chem., 1979, 44, 3769.
268 J. B. Holtwick, B. Golankiewicz, B. N. Holmes, and N. J. Leonard, J. Org. Chem., 1979,44, 3835.
269 A. Albert and A. M. Trotter, J. Chem. SOC., Perkin Trans. 1, 1979, 922.
270 I. Saito, S. Ito, H. Sugiyama, M. Akita, and T. Matsuura, Tetrahedron Lett., 1979, 4065.
271 B.-S. Huang and J. C. Parham, J. Org. Chem., 1979,44,4046.
7 Fused Systems containing Two Six-Membered Rings (6,6)

Treatment of the pyrido-pyrimidines (346) with pyrrolidine gives the 1,g-naph-
thyridines (347) (Scheme 133).272The meso-ionic oxazines (349) that are
formed by the reaction of chloroformyl-ketens with 2-pyridone undergo
cycloaddition reactions with dimethyl acetylenedicarboxylate or with phenyl
isocyanate, followed by loss of carbon dioxide, to yield quinolizines (350) and
pyrido-pyrimidines (348), respectively (Scheme 134).*" Pyrido-pyrimidines
(352) also result from the cycloaddition of anils of type (351) to ethyl vinyl ether
pJcozEt
(Scheme 135).274 0
L+R
Jc
o
2
E
t
R 0 H H
(346) (347)
Reagents: i, pyrrolidine, at 60-70 "C
Scheme 133
0
(348)
Reagents: i, MeO,CCGCCO,Me, ii, PhNCO

Scheme 134
aN=cHAr
(351)
+ H,C=CHOEt
Ar = Ph or o-HOC6H4
Scheme 135
+
(352) OEt
The reaction of the anilino-uracil (353) with benzaldehyde gives the 5 -

deazaflavin (354) in excellent yield (Scheme 136).275An alternative method of
synthesis of 5-deazaflavins is illustrated by the conversion of 6-aminouracil(355)
into (356) (Scheme 137).2765-Deazaflavins act as hydrogen acceptors by
addition to positions 1 and 5, and the 1,5-dihydro-compounds that are so formed
are readily re-oxidized in air. They have been shown to oxidize benzylamine to
ben~aldehyde.~~~
A complex series of reactions occurs when phenyl isocyanate is treated with
the phosphonium salt (357) in the presence of base, resulting finally in the
formation of the tricyclic compounds (358) and (359) (Scheme 138).278
272 I . Hermecz and Z. Meszaros, Heterocycles, 1979, 12, 1407.
273 T. Kappe, W. Golser, M. Hariri, and W. Stadtbauer, Chem. Ber., 1979, 112, 1585.
274 L. S. Povarov, Khim. Geterotsikl. Soedin., 1979, 1694.
275 F. Yoneda, T. Asano, K. Tsukuda, and A. Koshiro, Heterocycles, 1979,12, 691.
276 F. Yoneda, K. Mori, Y. Sakuma, and H . Yamaguchi, J. Chem. SOC.,Perkin Trans. 1, 1980, 978; F.
Yoneda, F. Takayama, and A. Koshiro, Chem. Pharm. Bull., 1979,27,2507.
277 F. Yoneda, Y. Sukuma, Y. Kadokawa, and A. Koshiro, Chem. Lett., 1979,1467.
278 L. Capuano, M. Bronder, K. Djokar, and I. Muller, Chem. Ber., 1980, 113, 395.
0 0 Ph3kH2C02Et
(353) (355)
1 li
li
py-----.--
i, ii
0
0 Ph
0
Me (358) R = O H [50%]
(354) (356) (359) R=NHPh [20°/0]
Reagents: i, PhCHO, PPA, at Reagents: i, PhCHO; ii, Reagents: i, PhNCO,
110°C EtO,CN=NCO,Et triethylarnine
Scheme 136 Scheme 137 Scheme 138
The reactions of pyrido[2,3-b]pyrazines and potassamide in liquid ammonia
have been further investigated. A rado of 1 : 3 of the product of dechlorination
(361) to that of ring-contraction (362) is obtained from 6-chloropyrido[2,3-b]-
pyrazine (360). Labelling experiments revealed the exclusive elimination of C-2
during the formation of the imidazole ring (Scheme 139).279
Scheme 139
An unusual 0-arylation occurs when the amino-nitros&uracil(363) is treated
with diphenyliodonium chloride; the diazabutadiene (364) is formed in 96%
yield. This undergoes regiospecific addition with enamines to form lumazine
derivatives, e.g. (365) (Scheme 140).280The different methods for ring-closing
3-aminopyrazine-2-carboxamideto 4-pteridones have been compared and
evaluated. No one reagent is superior in all cases.281
0 i M e N 5 N o p h 0
Me
(363)
- OAN
Me
(364)
NH
Me
(365)
Reagents: i, Ph,I+ C1-; ii, EtCH=CH-N

n
\p
Scheme 140
279 A. Nagel, H. C. van der Plas, G. Geurtsen, and A. van der Kuilen, J. Heterocycl. Chem., 1979, 16,
305.
E. C. Taylor and M. Inbasekaran, Heterocycles, 1978, 10, 37.
”’ A. Albert, J. Chem. SOC.,Perkin Trans. 1, 1979, 1574.
Enzymatic reduction (with dihydrofolate reductase and NADPH) of 7,8-
dihydro -6 -methylp terin (366) stereospecifically gives the (6S )-deriva tive (367).
It is probable that the reduction of 7,8-dihydrofolic acid gives a product of the
same stereochemistry (Scheme 141).282
H H
(366) (367)
Scheme 1 4 1
Intramolecular ring-closure of 6-(thiosemicarbazido)uracils(368) to pyrimido-

thiadiazines (369) is achieved in 32-75% yield by oxidation with N-chloro- or
N-bromo-succinimide. On heating the thiadiazines, sulphur is extruded and
pyrazolo-pyrimidines (370) are formed (Scheme 142).283
NR2NHCSNHR3
R' R' R2
(369) (370)
Scheme 142
8 Oxazines, Thiazines, and their Fused Derivatives

Oxazines and their Fused Derivatives.-Acid-catalysed rearrangement of the
cyclopropyl ketoximes (371) affords 5,6-dihydro-4H- 1,2-oxazines (372)
(Scheme 143).284
A new procedure for reductive cleavage of the N - 0 bond in N-acyl-3,6-
dihydro-2H-1,2-oxazines, e.g. (373), has been reported (Scheme 144); perform-
A*r
(371)
-+ Ar
(372) [ 2 9 4 7 % ]
Reagents: i, H', EtOH, heat
Scheme 143
Q+k,o OH
NKPh NHCOPh
(373) O [100%]
Reagents: i, PhCONHOH, [O]; ii, A1 amalgam, THF, H,O, at 0 "C
Scheme 144
282 W. L. F. Arrnarego, P. Waring, and J. W. Williams, J. Chem. Soc., Chem. Commun., 1980, 334
283 T. Naka and Y. Furukawa, Chem. Pharm. Bull., 1979, 27, 1965.
2R4
C. N. Rentzea, Angew. Chem., Int. Ed. Engl., 1980, 19, 199.
ance of this cleavage in good yield increases the synthetic potential of the
cycloaddition reaction of nitroso-compounds with d i e n e ~ . ~ ~ ~
Fusion of the 3-aryl-cyclopent[e][1,2]oxazines (374) at 200-280 "C gives
2-aryl-pyridines (375) in 40-80% yield; a plausible mechanism is depicted in
Scheme 145. Acid-catalysed ring-opening takes a quite different course, ring-
contraction occurring (Scheme 146).286
OHC
(374) (375)
Scheme 145
Thermal decarboxylation (at 150 "C) of 3-carboxy-5,6-dihydro-4H-1,2-

oxazines (376) proceeds with concomitant ring-opening to give y-hydroxy-
nitriles (377) in excellent yields.2874-Aryl-benzo[d][l,2]oxazin-l-ones (378)
have been prepared by treatment of monosubstituted benzenes with N -
hydroxyphthalimide under Friedel-Crafts conditions (AlCl,, heat for 15 min);
reaction occurs para to the substituent.288
R
F
Arylimino-1,3-oxathiins (380), obtained from benzoylthioacetanilides (379)

and phosgene, undergo slow acid-catalysed rearrangement to the corresponding
thioxo-l,3-oxazines (381) (Scheme 147).289
(380)
Reagents: i, COCI,, PhMe, heat; ii, H
'
, EtOH, at r.t.
Scheme 147
Isoxazolinones (382),upon reaction with nitrile oxides, undergo an interesting
ring-enlargement to give the 1,3-oxazines (383) in 30-85O% yields; the mechan-
ism has been discussed (Scheme 148).290
285 G. E. Keck, S. Fleming, D. Nickell, and P. Weider, Synth. Commun., 1979, 9, 281.
286 R. Faragher and T. L. Gilchrist, J. Chem. Soc., Perkin Trans. 1, 1979, 258.
287 T. L. Gilchrist and T. G . Roberts, J. Chem. SOC.,Chem. Commun., 1979, 1090.
288 A. F. M. Fahmy, A. Nawal, and M. Oraby, Egypt. J. Chem., 1976,19,223.
289 W . Zankowska-Jasinka, Z. Kamela, and U. Zieba, Pol. J. Chem., 1979,53, 1251.
290 Perkin Trans. 1, 1979,
F. Risitano, G . Grassi, F. Foti, F. Caruso, and G. Lo Vecchio, J. Chem. SOC.,
1522.
6 :tJph
R2/ NH + PhCN + ‘HN02’

0
(382) (383)
Reagents: i, Excess PhC&-0, PhH, heat
Scheme 148
N-Methylisoxazolidines, e.g. (384), are smoothly converted into N-hydroxy-

tetrahydro-1,3-oxazines,e.g. (385)’ in good yield by oxidation with m-chloroper-
benzoic acid; in one case the intermediate nitrone can be trapped (as an adduct
with methyl acrylate) (Scheme 149).291
TI0 Me
Me
W O
0-
H
Me OH
(384) Scheme 149
N-Methyl-tetrahydro-1,3-oxazineexists as a mixture of ring and open-chain

tautomers in TFA ; the analogous oxazolidine behaves similarly. Of interest is
the fact that ring-chain interconversion is more rapid for the oxazolidine, in
converse to the predictions of Baldwin’s vectorial rules.2o3
The first examples of the ten-electron cyclopent[d][ 1,3]oxazine system, e.g.
(388)’ have been synthesized, in moderate yields, from cyclohexa-2,4-dienimines
(386), as exemplified in Scheme 150. The intermediate ketenimines (387) can be
observed spectroscopically (Y = 2020 cm-’) if the reaction takes place at low
temperature (77 K).292
Salicylic acid, upon treatment with triphenylphosphine dithiocyanate, gives the
Ph O P h
NHCOMe
ph@h OAc
11
+
Ph
p..
benzo[e]-l,3-oxazine (389);293the cadmium-acetate-catalysed addition of N- ( p -
c+ NCOMe
NCOMe
Ph OAc
+--
Ph N
(388)
Reagents: i, Pb(OAc),; ii, hv, PhH; iii, at r.t.
Scheme 150
*” N. A . Le Bel, M. E. Post, and D. Hwang, J. Org. Chem., 1979,44, 1819.
2y2 H. H. Eckhardt and H. Perst, Tetrahedron Lett., 1979, 2125.
293 T. Tamura, J. Synth. Merhods, 1980, 6, Abstr. 75 339V.
(389) (390)
hydroxypheny1)salicylamide to acetylene also gives a benzo[e]- 1,3-0xazine
(390).294
A novel and interesting route to 2-aryl-4-oxo-benzo[d][l,3]oxazines (392)
is furnished by the thermal reaction of o-azidobenzoic acid with benzaldehydes
(Scheme 151). The reaction is thought to proceed uia a novel type of cyclo-
adduct (391) rather than via a nitrene, as the temperature required (ca. 110 "C)
is significantly below that at which the azide decomposes (145 "C). Yields
are good, the reaction works with electron-rich and electron-poor aldehydes,
and ortho-azidobenzamides react similarly, giving quinazoline derivatives
(see p. 256).'05
+
ArCHO
Ar = Ph, 4-MeOC6H4, or 4-N02C6&
Scheme 151
Mandelaldehyde, PhCH(OH)CHO, can be condensed with N-phenyl-
ethanolamine under acid catalysis to afford the 5,6-dihydro- 1,4-oxazine (393)
(80%); none of the isomeric oxazolidine is formed.220Oxidation of isatins with
peroxodisulphate gives excellent yields of 2,3-dioxo-benzo[b]-l,4-oxazines
(394), in contrast to the formation of isatoic anhydrides by oxidation with a
Benzo[b]-1,4-oxazines that are functionalized with methylene at
position 2, i.e. (395): are obtained in good yields by the mercuric-oxide-promoted
cyclization of o-(propargylamin~)phenols.~~~
(393) (394) (395)

A new, fairly general, route to 3H-phenoxazin-3-ones (396) consists of the
condensation of resorcinols with substituted o-nitrochlorobenzenes, followed by
reductive cyclization of the resulting nitro-ethers (Scheme 152). Under the
2y4 G. G. Skvortsova, Z. V. Stepanova, and L. V. Andriyankova, Chem. Heterocycl. Compd. (Engl.
Transl.), 1979,15, 1036.
295 G. Reissenweber and D. Mangold, Angew. Chem., Znt. Ed. Engl., 1980,19,222.
296 M. Yamamoto, J. Chem. SOC.,Perkin Trans. 1, 1979,3161.
K' R3
Reagents: i, ArOK, Cu,O, N-methylpyrrolidine. at 150 " C ; ii, Zn, aqueous NH,CI,
1,2-dirnethoxyethane
Scheme 152
reaction conditions, reduction of the first-formed phenoxazinones (396) to

3-hydroxyphenoxazines may occur; the latter are easily re-oxidized, simple
aeration often sufficing. Overall yields of this ring system, which is a central
structural feature of the actinomycin antibiotics, can be very
Thiazines and their Fused Derivatives.-A new synthetic route to 3,6-dihydro-
1,2-azathiabenzenes has been established; thiazyl fluoride (F-SEN) reacts with
perfluorobutadiene to give an almost quantitative yield of perfluoro- l h 4,2-
thiazacyclohexa-1,4-diene(397). It should be noted that alkyl-butadienes react
explosively. The C-S bond of this stable, colourless liquid can be cleaved with
halogens (e.g. see Scheme 153).298
F
I
hv
s, C1
+ 2C1, +
F+CI
"F F
[5 0 "/o ]
Scheme 153
Another novel cycloaddition route to 1,2-thiazines is most interesting in that

it furnishes circumstantial evidence for the formation of the unknown thio-
nitrosomethane (MeNS) (Scheme 154). Other thiazines may be obtained by
using differently substituted oxaziridines, and other thiirans can act as the sulphur
source; the alkene is always obtained with retention of configuration. An attempt
to observe thionitrosomethane spectroscopically by performing the desulphuriz-
ation at -20 "C was U ~ S U C C ~ S S ~ U I . ~ ~ ~
Sensitized photo-oxidation of 2-aryl-3,5-dimethyl-2H-1,2-thiazine1 , l -
dioxides (398) gives 5,6-dioxygenated products (399); these compounds are
Me
\
N=S=N
PhCHO + [MeNS]
Y \
M€
[ 100°/0]
Reagents: i , CHCI,, at r.t., absence of trap; ii, CHCI,, at r.t., butadiene

Scheme 154
2q7 C. W. Bird and M. Latif, Tetrahedron, 1980, 36, 529.
298 W. Bludssus and R. Mews, J. Chem. SOC., Chem. Commun., 1979, 35.
299 Y. Hata and M. Watanabe, J. Org Chem., 1980,45, 1691.
Me\
cyAr
SO,
M e C Y A r
so2
2
-so, Me
QAr O H
Me
277
HO
(398) 0 0
(399) (400)
Reagents: i, 0,, rnethylene blue, MeOH, h v ; ii, Et,N, Et,O, heat
Scheme 155
unstable towards base, losing SO2 to give l-aryl-5-hydroxy-pyrrolin-2-ones

(400) (Scheme 155).”0°
The 1,2-azathianaphthalene and 6,5-azathiaphenanthrene systems have been
synthesized for the first time (e.g. see Scheme 156); the azathiaphenanthrene
(40 1) undergoes ring-expansion to the thiazepine (402) upon t h e r m o l y s i ~ . ~ ~ ~
(401) H
(402)
Reagents: i, NCS, CH,CI,, at -50 “C; ii, aqueous KOH; iii, xylene, heat
Scheme 156
2-Amino-1,3-thiazinium salts (404) are simply prepared, in good yield, by

treatment of the iminium salt (403) with the appropriate secondary amine
(Scheme 157).’(’’
An interesting route to 4-imino-1,3-thiazines (406; X = CH) lies in the attack
of unsaturated carbon nucleophiles (e.g. cyanide and methyl propiolate anion)
upon the isothiazolium salt (405; X = CH), as shown in Scheme 158. The
1,2,5-thiadiazolium salt (405; X = N) reacts similarly, giving (406; X = N).303
P h p A M e 2
N *c c10,-
+ N H R 2 -+ Phl(\\l
N d S + c10,-
*S NR2
(403) (404)
Scheme 157
z (405) (406)
Scheme 158
300 E. Fanghanel, E. A. Do Nascirnento, R. Radeglia, G. Lutze, and B. Bode, J. Prakt. Chem., 1979,
321,946.
301 M. Hori, T. Kataoka, H. Shirnizu, and K. Matsuo, Tetrahedron Lett., 1979, 3969.
302 J. Liebscher, J. Synth. Methods, 1980, 6, Abstr. 75 135V.
303 J. Rokach, P. Hernel, Y. Girard, and G. Reader, Tetrahedron Lett., 1979, 1281.
5,6-Dihydro-4H-1,3-thiazines (409) have been prepared by a method which
would appear to be of general applicability. a-Lithio-isocyanides (407) are
treated with episulphides to afford y-mercapto-isocyanides (408); these cyclize
slowly at room temperature and rapidly if there is catalysis by copper(1) (Scheme
159). This route has, in the past, been applied to the synthesis of 1,3-0xazines.~"~
(407) R' R2
(408) (409)
Reagents: i, R2&R' , THF, at r.t.; ii, HOAc, at -20°C; iii, Cu,O, PhH, heat
Scheme 159
A novel a-diazo-sulphoxide-thioester rearrangement is observed upon treat-

ing 2-diazocephem S-oxides (410) with rhodium acetate; the resultant 2-0x0-
cephems (411) (10--40%) may arise via the formation of a carbene followed
by oxygen walk (Scheme 160).3"5
0
1
(410)
Reagents: i, rhodium(i1) acetate, THF, at 0 "C
Scheme 160
The reaction between benzimidazolethione (412) and DMAD has been

investigated in some detail (Scheme 161); the results should help to clarify a
somewhat confused area of chemistry.306The thiazine (415) is the final product,
even at room temperature; if the reaction mixture is analysed after a shorter
period of time, both the intermediate adduct (413) and the thiazole (414) can be
isolated. The thiazole undergoes quantitative conversion into the thiazine (415)
upon refluxing in methanol overnight; this rearrangement may be catalysed by
base (NaOMe or MeOH), in which case it is complete in a few minutes at room
temperature.
Oxidation (with H 2 0 2 and HOAc) of 2-methylthio-4-thioxobenzo[d]-
[1,3]thiazine is reported to occur solely at the thiocarbonyl sulphur to give the
corresponding thiocarbonyl oxide (67'/0).~'~
Treatment of 3-alkyl-2-(iodomethyl)thiazolium iodides (416) with methanolic
potassium hydroxide results in clean ring-expansion to 4-alkyl-2H-1,4-thiazin-
3-ones (417). The overall yields from this new synthetic route (Scheme 162) are
47-75 O/O, based on the starting t h i a ~ o l e . ~ "
304 U. Schollkopf, R. Jentsch, and K. Madawinata, Liebigs Ann. Chem., 1979,451.
305 C . F. Ebbinghaus, P. Morrissey, and R. L. Rosati, J. Org. Chem., 1979,444697.
306 J. J. Wade, J. Org. Chem., 1979, 44, 1817.
307 S . Leistner and G. Wagner, Z. Chem., 1980, 20, 187.
308 M. Hojo, R. Masuda, S. Kosaku, and K. Nagase, Synthesis, 1979, 272.
H
H
(412) (413)
'
I \bs
d C O z M e
-,iii
0
C0,Me
(415) (414)
Reagents: i, DMAD, MeOH, at r.t.; ii, MeOH, at r.t.; iii, MeOH, heat
Scheme 161
(4 16) (417)
Reagents: i, RI; ii, I,, CH,Cl,, at 0°C; iii, Et,N; iv, KOH, MeOH, at r.t.
Scheme 162
9 Other Oxygen- and Sulphur-containing Systems
Representatives of the new 1,3,4-dioxazin-5-one system have been prepared
( 3 5 4 0 % ) by condensation of dimethyl acetals with a-hydroxy-hydroxamic
acids (Scheme 163); the acetals must be used, because the parent aldehydes fail
to condense.309
R< ,OH
+ ArCH(OMe), -
Ph R' Ph R'
Reagents: i, PTSA, PhH, heat
Scheme 163
The 4-oxo-1,2,3-oxathiazine 2,2-dioxides (418), known to be formed from
ketones R'COCH2R2 and FSI (FSI is FS02NCO), can be chlorinated to afford
the 4-chloro-derivatives (419). The attack of nucleophiles upon these latter
compounds occurs at the 6-position, giving P-functionalized acrylonitriles (420)
and (421) (20-60%); the cis: trans ratio varies from 0: 100 to 95 : 5 (Scheme
164).310
Thermolysis (at 120-140 "C)of 2-aryl-6H-1,3,5-oxathiazines (422), which
can now be synthesized with a variety of ~ u b s t i t u e n f sgives
, ~ ~ ~1,3-thiazadienes
~
309 D. Greffen, Heterocycles, 1979, 12, 519.
310 J. Sander and K. Claus, Angew. Chem., Int. Ed. Engl., 1980, 19, 131.
311 ( a )C. Giordano, A . Belli, R. Erbea, and S. Panossian, Synthesis, 1979, 801; ( b ) C. Giordano, A.
Belli and L. Abis, Tetrahedron Lerr., 1979, 1537.
280 He teroc yc 1ic Chemistry
(4 18) (419) (420)

Nu = PhNH, PhO, PhS, or EtS
Reagents: i, PCI,, CCI,, heat; ii, NuH, base, CH,CI,, at r.t.
Scheme 164
(423); these dimerize, under the reaction conditions, to thiadiazines (424) in
yields of l6-61% (Scheme 165). No thiazetes are obtained; this is in contrast
to the known cyclization of the bis(trifluoromethy1)thiazadienes (425) (similarly
generated) to a four-membered ring.,’ l b
Scheme 165
The N-acyl-imine (426) cyclo-adds to aromatic aldehydes and nitriles to give

1,3,5-dioxazines and 1,3,5-oxadiazines, re~pectively.”~ Treatment of divinyl
sulphide with thiourea affords the 1,3,5-dithiazine (427).313
Me
The thiadiazine (428) (see p. 277) undergoes a quantitative rearrangement

to the tri-imino-thiazole (429) upon treatment with base.,’, Thermal extrusion
of ‘NH’ from the benzo[e]-1,2,4-thiadiazine(430) is far more difficult than from
the analogous oxadiazine, which loses ‘NH’ upon refluxing in benzene. The
reaction can, however, be performed at room temperature by the use of
triphenylphosphine, which forms a complex with (430); this complex is converted
into the thiazole (431) (98%) and triphenylphosphine oxide upon elution
through silica (Scheme 166).,14
Benzo[e]-1,2,4-thiadiazine 1,l-dioxide has been shown to prefer the 4 H -
structure (432).,15 A new, simple route to 3-0x0-derivatives of this system has
been developed; anilines are added to CSI (CSI is ClS0,NCO) and the resultant
N-chlorosulphonyl-ureas cyclized with AlCl,. Yields are good tcl excellent, and
312 Z. V. Safronova, L. A. Simonyan, Yu.V. Zeifman, and N. P. Gambaryan, Xzv. A k a d . Nauk. SSSR,
Ser. Khim., 1979, 1826 (Chem. Abstr., 1980,92,41 900).
’13 B. A. Trofimov, G. M. Gavrilova, G . A. Kalabin, V. V. Bairov, and S. V. Amosova, Khim.
Geterotsikl. Soedin., 1979, 1466 (Chem. Abstr., 1980, 92, 94 357).
314 V. W. Bohnisch, T. L. Gilchrist, and C. W. Rees, J. Chem. SOC., Perkin Trans. 1, 1979, 2851.
315 P. Jakobsen and S. Treppendahl, Tetrahedron, 1979.35, 2151.
(430) (431)
0 2
aNyo
Reagents: i, p-MeOC,H,OMe, at 213 "c,for 16 h
(432)
Scheme 166
~ " " " 2 i,ji ~"""1 R2 iii
--* --+
NH SOZNH,
S'
R' R' 0 2 R'
Reagents: i, CSI, EtNO,, at -40°C; ii, AICI,, heat; iii, conc. HCI, heat
Scheme 167
the products undergo acid hydrolysis to o-amino-sulphonamides (Scheme

167).316
A general method for preparing thia-analogues of cytosines and thymines, with
the 2-carbonyl group replaced by the bio-isosteric sulphonyl group, has been
reported. 3-Aminoisoxazole is treated with a sulphamoyl chloride and the
isoxazole ring is then hydrogenolysed; base-catalysed cyclization, with elimina-
tion of water, affords the thiacytosines (433) (Scheme 168) in moderate to good
yields.317 Similarly, 5-amino-3-methyloxazole gives the thiathymines (434),
ammonia being eliminated in this case.
0
P:Hso2NHR
0
+
i r
OH
y
SO,
I
NHR
H +
ii F y,SO*
H
N
R
Mefi,. N
R
(433) (434)
Reagents: i, H,, Raney nickel; ii, NaOMe, HOMe
Scheme 168
Alternatively substituted thiathymines (435) have been prepared from

methoxymethylene malonate and monoalkylsulphamides, and also from amino-
alkylidene malonates with sulphamoyl chlorides ; an example is depicted in
Scheme 16ge3'*Some of the chemistry of these systems has been described.
0 0
(435)
Scheme 169
316 Y. Girard, J. G . Atkinson, and J. Rokach, J. Chem. SOC.,Perkin Trans. 1, 1979, 1043.
3'7 H. A. Albrecht, J. F. Blount, F. M. Konzelmann, and J. T. Plati, J. Org. Chem., 1979, 44, 4191.
318 H. Hansen, K.-H. Konig, and W. Rohr, Liebigs A n n . Chem., 1979, 950.
The first examples of the 3H-benzo[c][ 1,2,6]thiadiazine system (1H-deriva-
tives are known) have appeared in two independent reports. Oxidation (by DDQ)
of the 1,4-dihydro precursor affords (436) (30'/0),~~' and elimination of
methanol from the 4-methoxy-derivative gives (437).320Spectroscopic methods
have revealed that a positive charge is localized on N-3.320
(437)
The oxathiadiazine (439) is known to undergo thermal dissociation to

acetonitrile and (438), which can be trapped with dienophiles (e.g. acetylenes).
Heating (439) with ynamines, however, results in nucleophilic attack by the
ynamine upon the ring system to give the 1,2,6-thiadiazines (440), after a
ring-opening-ring-closure sequence (Scheme 170).321
z2
-
/s\
0 2
02s* N N i N' \ N C 0 2 M e
MeCN + N -
-Mey )OMe M e u N R 2 2
OAOMe 0 R'
(438) (439)
Reagents: i, R1C=CNR22
Scheme 170
1,3,5-Thiadiazines (441) are obtained by the action of secondary amines on

benzoyl i s ~ t h i o c y a n a t e Treatment
.~~~ of isothioureas with CSI gives 1,2,4,6-
thiatriazines (Scheme 171); 2-aminopyridine and 2-aminopyrazine react
similarly. Heterocyclic betaines may be obtained if the isothiourea is NN'-
disubstit~ted.~'~
SMe
Ph
N-N
H
(441) Reagents: i, CSI, MeCN, at 0°C; ii, EtPr',N, at 20°C
Scheme 171
319 R. G. Pews, J. Heterocycl. Chem., 1979, 16, 1069.

320 A. Parg and G. Hamprecht, Liebigs Ann. Chem., 1979, 1130.
321 J. A. Kloek and K. L. Leschinsky, J. Org. Chem., 1980, 45, 721.
322 L. Beyer, J. Synth. Methods, 1980, 6, Abstr. 75 387V.
323 S. Karady, J. S. Amato, D. Dortmund, A. A. Patchett, R. A. Reamer, R. J. Tull, and L. M.
Weinstock, Heterocycles, 1979, 12,1199.
Six-Membered Rings: Other systems 283
PART 11: Other Six-Membered Ring Systems by G. P.Ellis
1 Books and Reviews

Synthetic approaches to the 4H-pyran ring have been reviewed' as also have
spiropyrans capable of reversible opening of the pyran ring.2 The reactions of a-
and y-alkyl groups of pyrylium salts have been ~ u r v e y e dChemical
.~ and biologi-
cal aspects of plants of the family Compositae are discussed in a comprehensive
Flavonoids are the subject of numerous reviews: their chemistry, metabol-
ism, and biological effect^;^ their biosynthesis;6 chalcone epoxides;' and flavan-3-
01s.~A monograph has been published on the analysis of cannabinoids in
physiological fluids.' The biosynthesis of coumarin and of furocoumarins" and
the xanthones present in lichens" are subjects of reviews. Brazilian woods
contain many types of compounds, including several oxygen heterocycles, and
these have been reviewed.'* The synthesis, properties, and uses13 and the
acid-catalysed transformation^'^ of 1,3-dioxans have been discussed.
2 Heterocycles containing One Oxygen Atom

Reduced Pyrans.-6-Substituted 3,4-dihydro-2H-pyrans (2) have been obtained
in high yields by an intramolecular Wittig r e a ~ t i o nof
' ~the phosphonium bromide
(1).During the synthesis of the diastereoisomeric pyranols (4) and ( 5 ) , it was
found that distillation of the ethylene ketal(6) of the ketone (3)gave the dipyran
(7) in good yield.I6 P-Allenic alcohols (8) are cyclized at room temperature in
-65% yield to 5,6-dihydro-2H-pyrans (9)by treatment with AgN03 and CaCO,
in aqueous dioxan.17 The cyclizing agent in a similar synthesis of the 5,6-
dihydropyrans (11)from (10) in about 60% yield was BF3.18
Ph36(CH,),Br Br-
(1)
+ RC0,Na - OR (2)
C. Seoane, J. L. Soto, and M. Quinteiro, Heterocycles, 1980, 14, 337.

E. R. Zakhs, V. P. Martynova, and L. S. Efros, Khim. Geterotsikl. Soedin., 1979, 435.
V. V. Mezheritskii, A . L. Wasserman, and G. N . Dorofeenko, Heterocycles, 1979, 12, 51.
'Biology and Chemistry of Compositae', ed. V. H. Heywood, J. B. Harborne, and B. L. Turner,
Academic Press, London, 1977.
' H. Wagner, Schriftenr. Bundesapothekerkammer Wiss., Fortbild., Gelde Reiche, 1978,6, 81.
H. Grisebach, Recent Ado. Phytochem., 1977,12 (Biochemistry of Plant Phenolics), p. 221.
G . Litkei, Recent Dev. Chem. Nat. Carbon Compd., 1979,9, 293.
' J. Masquelier, J. Michand, J. Laparra, and M. C. Damon, Int. J. Vitam. Nutr. Res., 1979, 49, 307.
ACS Symposium Series, No. 98, 'Cannabinoid Analysis in Physiological Fluids', American Chemical
Society, Washington, 1979.
lo S. A. Brown, Planta Med., 1979, 36, 299.
' I E. G. Sundholm, Acta Unio. Ups. Abstr. Uppsala Disc. Fac. Sci., 1979, 526.
0. R. Gottlieb and W. B. Mors, J. Agric. Food Chem., 1980, 28, 196.
l 3 M. Saur and V. Ruzicka, Sb. Vys. Sk. Chem.-Technol. Praze, Org. Chem. Technol., 1978, C25, 77.
l4 D. L. Rakhmankulov, E. A. Kantor, and R. A . Karakhanov, Heterocycles, 1979, 12, 1039.
l 5 A. Hercouet and M. LeCorre, Tetrahedron Lett., 1979, 5 .
l 6 C. Anselmi, G. Berti, G. Catelani, F. Coppa, and L. Monti, G a z z . Chim. Ital., 1979, 109,41.
l 7 L. I. Olsen and A. Claesson, Synthesis, 1979, 743.
J. Grimaldi and A. Cormons, C . R . Hebd. Seances Acad. Sci., Ser. C, 1979,289, 373,
J
ButC H(CH 2 ) 3CM e --+ B u t O 0 M e Mrgy\"rB~'
I
OH "U
O 0 LJ
OH
(8) R4 = H (9) R4 = H
(10) R' = H , R 4 = Me (11) R4 = Me
Pederamide (12) is an important intermediate in the projected total synthesis
of pederin (13), a component of the vesicant of the beetle Paederus fuscipes.
trans-2-Butene epoxide has been converted (in 16 steps) into pederamide. One
of these involved the conversion of the tetrahydrofuran (14) into the pyran-2-one
(15) in 96% yield.'' Synthetic studies on lasalocid A (16) have continued with
the use of carbohydrates as substrates for the construction of both furanoid and
pyranoid rings of the antibiotic.*'
Me
Me /
pA!ON HR
MeQoMe
Me CH,CO,Me
(12) R = H
(13) R = -CH
, CH2 OH (14)
~ ~ ~ , CI H C H 2 O w ~ ~
Me Me
Et
l9 M . A, Adams, A. J. Duggan, J. Srnolanotf, and J. Meinwald, J. A m . Chem. SOC.,1979, 101, 5364.

2o R. E. Ireland, S. Thaisrivongs, and C. S . Wilcox, J. A m . Chem. Soc., 1980, 102, 1155.
The absolute configuration, i.e. ( S , S ) ,of a tetrahydropyran (17) that is present

in civet (Viuerra ciuetta) has been determined, using a chiral shift reagent
[Eu(hfc),] and 360 MHz n.m.r. spectroscopy in comparison with a synthetic
sample of (+)-(S,S)-(l7) and its methyl ester.21 X-Ray analysis was applied to
the determination of the conformation of the violet form of cunaniol acetate (18),
which was shown to have an undistorted chair form with both substituents
An e.p.r. spectral study2, has shown that the radical which is formed
from several stereoisomeric 2,4-disubstituted tetrahydropyrans is the same,
namely the cis-2-alkoxy-4-methyltetrahydropyran-2-yl radical.
(19) R = Li
(20) R = CH(0H)Ar
(21) R = 3-oxocyclohexan-1-yl
Gas-phase pyrolysis of 3,6-dihydro-2H-pyran at about 350 “C gave a quan-
titative yield of butadiene and f ~ r m a l d e h y d eDihydropyranyl-lithium
.~~ (19),on
reaction with carbonyl compounds, gives good yields of hydroxyalkyl derivatives
(20); in the presence of Cu12, it undergoes conjugate addition to @unsaturated
ketones to give ketones such as (21).2sThe reaction of 2,3-dihydro-4H-pyran
with t-butyl hydroperoxide in the presence of CuCl gave 4-t-butylperoxy-2,3-
dihydro-4H-pyran, which on catalytic reduction yielded the 4-hydroxy-deriva-
tive. In this reaction, a proton at position 4 is ten times more reactive than one in
the 2 - p o ~ i t i o n2-Acyl-5,6-dihydro-4H-pyrans
.~~ have been reduced at a mercury
cathode in acid medium to give the tetrahydro-derivative. In basic medium, the
acyl carbonyl is reduced to the alcohol. 3-Chloro-5,6-dihydro-4H-pyran loses the
halogen at the ~ a t h o d e . ~An
’ 0-tetrahydropyranyl group may be removed under
mild conditions and in high yield by treatment with acid-washed Dowex 50W-
X8 .28
Pyrans.-Ten highly substituted 4H-pyrans (23 ; Ar’ = Ph, MeOC6H4, C1C6H4,
or NO2C6H4;Ar2 = Ph or 4-N02C,H4) have been synthesized, in high yields,
by cyclization of the keto-ester (22) with malononitrile and ~iperidine.~’
A mild
and efficient process of producing the perchlorinated pyran (26) consists of
cyclization of the alcohol (24) with KOH and MeOH, uia the intermediate (25).,’
An improved and safer method of preparing bipyranylidene (27) and similar
compounds than was hitherto available is to heat 2,6-diphenylpyrylium perchlor-
ate and a catalytic amount of triphenylphosphine in pyridine at 100°C. The
21 B. Maurer and W. Thornrnen, Helv. Chim. Acta, 1979, 62, 1096.
22 G. P. Jones and P. J. Pauling, J. Chem. SOC.,Perkin Trans. 1, 1979, 1482.
23 V. Malatesta, R. D. McKelvey, B. W. Babcock, and K. U. Ingold, J. Org. Chem., 1979,44, 1872.
24 H. M. Frey and S. P. Lodge, J. Chem. SOC.,Perkin Trans. 2, 1979, 1463.
25 J . Ficini, P. Kahn, S. Falou, and A. M. Touzin, Tetrahedron Lett., 1979, 67.
26 C. Filliatre, J. J. Villenave, and C . Manigand, J. Heterocycl. Chem., 1979, 16, 513.
” A. Lebouc, H. Van Rooijen, 0.Riobe, G. LeGuillantoin, and J. Delaunay, Electrochim. Acta, 1979,
24, 1119.
B. Beier and B. P. Mundy, Synth. Commun., 1979, 9, 271.
29
M. Quinteiro, C. Seoane, and J. L. Soto, Rev. Roum. Chim., 1979, 24, 859.
30 A. Roedig and H. Gopfert, Chem. Ber., 1980, 113, 806.
Ho\
Ar 'CH=CCOAr C12C CHCCl,
I I1 I
C02Et CO2Et CIC, +CCl
C C1
(22) Ar' CI
(24) (25) R' = H, R2 = CC13
(23)
(26) R I R ~= cci2
+
/ CO,Me
R2
R', R2 = alkyl (28)
method was extended to several other pyrylium and flavylium salts and their
sulphur analogues. Some pyrylium salts did not r e a ~ t . ~ '
2-Pyrones.-5,6-Dihydro-2H-pyran-2-ones (28; R', R2 = alkyl) have been
synthesized in good yield by a Knoevenagel reaction between a 3-hydroxylated
aldehyde and a malonic ester in the presence of TiC14 and ~ y r i d i n e Bis-2-
.~~
pyrones in which the two rings are joined by an alkyl chain or a benzene ring,
e.g. (30),have been synthesized in high yield from the tetrachloride (29) and a
diacid chloride; e.g. terephthaloyl chloride.33Ullmann reaction conditions, when
applied to iodo- or bromo-pyrones (31), have given moderate yields of 3,3'-bi-(2-
pyrones) (32).34A constituent (34) o f Euphorbia biglandulortc has been synthe-
sized from 4,4-dimethyltetrahydrofuran-2,3-dione(33) in three A plant
(Iboza riparia) that grows in Rwanda and which is used medicinally contains
several 2-pyrones, such as 6-(3-acetyloxyhept-l-enyl)-5,6-dihydro-2-pyr0ne.~~
The isolation and structural determination of the antibiotic malyngolide (35)
from the Hawaian alga Lyngbya majuscula has been d e ~ c r i b e d . ~The
' reactions
A r u . 4 r ~ o ~ A&ryo
/x / \ /
0 c72
(31) (32) (33)
C 0 2 - Ca
(34)
3' G . A. Reynolds, C. H. Chen, and J. A. Van Allan, J. Org. Chem., 1 9 7 9 , 4 4 4 4 5 6 .
32 G . Falsone and B. Spur, Liebigs Ann. Chem., 1979, 751.
33 A. N . Akopyan, A. M. Saakyan, and A. D. Tatevosyan, Zh. Org. Khim., 1979,19, 505.
34 S. V. Sokolovskaya and L. K. Moldovanova, Khim. Geterotsikl. Soedin., 1979, 173.
35 G. Falsone and B. Spur, Liebigs Ann. Chem., 1979, 923.
36 L. Van Puyveide, S. Dube, E. Uwimana, C. Uwera, R. A. Dommisse, E . L. Esrnans, 0.Van Schoor,
and A. J. Vlietinck, Phytochernistry, 1979, 18, 1215.
37 J. H. Cardllina 11, R. E. Moore, E. V. Arnold, and J. Clardy, J. Org. Chem., 1979, 44, 4039.
R
NC T . ' ' ?
MeoocH
H' (35)
C9h9
2o
MeO,C\
of xanthyrones continue to be in~estigated,~'

(36)
c/o
Me Ac\
especially their enolizing abilities

and their chelation of magnesium. The 3-acetyl group of compounds such as (36)
C0,Me
(37)
OMe
has been shown to be enolized and hydrogen-bonded, but its replacement by

3-C02Me prevents this. The intriguing chemical behaviour of pyrones such as
(37) in the presence of varying amounts of Mg(OMe):! is explained by consider-
ation of the sites at which an anion can form. Refluxing (36; R = C02Me) with
water gave methyl 5-acetyl-2-hydroxybenzoate74-hydroxyacetophenone, and
methyl ~ y a n o a c e t a t e . ~ ~
2-Pyrones (38) are oxidized, in high yield, by singlet oxygen to the
endoperoxide (39), which may be quantitatively decarboxylated to the 1,2-
diacyl-ethylenes (40) on heating.40 Alkylation of alkali-labile primary or secon-
dary alcohols is now possible under neutral conditions, using a betaine that is
generated in situ from diethyl azoformate and triphenylphospine. In this way,
4-hydroxy-2-pyrones are 0-alkylated in very good yield at 0-18 "C. Tertiary
alcohols give a poor yield.41
p R4
3-Pyrones.-The reaction of the 3-pyrone (41) with 4-bromophenol gave the

2-(ary1oxy)pyrone (42) as the main
4-Pyrones.-A one-pot conversion of furfuryl alcohol into 3-hydroxy-2-methyl-
4H-4-pyrone (maltol) in 70°% yield has been effected by chlorination and
heating.43Tetraketones [such as (43)] undergo self-condensation, on heating for
RO 0 OH
(41) R
XI+*
= PhCO
PhCCH,C
(43)
I1 I
Ph
(42) R = p-BrC6H4 0
(44)
38 G . P. Ellis, in 'Heterocyclic Chemistry', ed. H. Suschitzky and 0.Meth-Cohn (Specialist Periodical
Reports), The Royal Society of Chemistry, London, 1980, Vol. 1, p. 333.
39 S. R. Baker, L. Crombie, and R. V. Dove, J. Chem. SOC., Chem. Commun., 1979,666.
40 W. Adam and I. Erden, J. A m . Chem. SOC.,1979,101,5692.
41 E. Suzuki, B. Katsuragawa, and S. Inoue, J. Chem. Res. ( S ) , 1979, 110.
42 G . Grynkiewicz, J. W. Krajewski, Z. Urbanczyk-Lipkowska, P. Gluzinski, and A. Zamojski, Pol. J.
Chem., 1979,53,2025.
43 P. D. Weeks, T. M. Brennan, D. P. Brannegan, D. E. Kuhla, M. L. Elliott, H. A. Watson, B.
Wlodecki, and R. Breitenbach, J. Org. Chem., 1980, 45, 1109.
10 days in carbon tetrachloride, to yield the 2,3-dihydro-4-pyrone (44).44
Another type of highly substituted 4-pyrone (48) has been prepared by hydrolysis
of the bicyclic pyrylium salt (47), which was obtained by condensation of the
4-0x0-ester (45) with an anhydride (46) in an alcohol and perchloric
a@-Acetylenic 1,3-diketones (prepared by an improved method) have been
cyclized to 4-pyrones by hot hydrochloric acid, and the chemical and spectral
properties of the pyrones have been Analogues of the neurochemically
important compound 4-aminobutyric acid (49) in which three of the carbon atoms
are part of a 4-pyrone ring (50) have been synthesized and found to have
muscle-relaxant a~tivity.~’Ozonization of 4-methylenetetrahydropyran-3-01
( 5 1) (obtained by photo-oxygenation of 5,6-dihydro-4-methyl-2H-pyran)
II
ArC(CH,),CO,Me
0 + (EtCO),O +
HCIO, pze
produced a 43% yield of the 4-pyrone (52); on standing, this dimerized to the
hemiacetal (53).48
0
(47)
C104-
2
CO,H 0
NJH2
il’ OH
OH
0
(49) (53)
(52) R = 0
Ring-cleavage of 4-pyrones by hydrazines to give pyrazoles is now well

established; some recent variations include the reaction of 2,3-dihydro-4-
pyrones (54) with phenylhydrazine, in which an intermediate phenylhydrazone
( 5 5 ) and an alkenyl-pyrazole (56) were isolated,49 and of the formation of two
isomeric pyrazoles (58) and (59) from the 2,3-dihydro-4-pyrone (57).50 A
bipyrazole (60) was isolated from the reaction of ethyl 2,6-dimethyl-4-oxopyran-
3,5-dicarboxylate and phenylhydra~ine;~’ the same pyrone, when treated with
piperidine, gave an unexpected product (61).” Several Knoevenagel-type con-
densations of 5-methoxy-4-oxopyran-2-carboxaldehyde(comenaldehyde) have
been described.52Tetrahydro-4-pyrones (62; R’ = H or Me, R2 = alkyl) react
with ethyl 2-chloropropionate and sodium to give the spiro-compounds (63),
from which the ketones (64) were d e r i ~ e d . ’ ~
44 K. Balenovic and M. Poje, Tetrahedron Lett., 1979, 2175.
45 Yu. I. Ryabukhin, V. V. Mezheritskii, V. 1. Dulenko, N. I. Basina, and G. N. Dorofeenko, Khim.
46 I. El S. El-Kholy, M. G. Marei, and M. M. Mishrikey, J. Heterocycl. Chem., 1979, 16, 737.
4 7 J. G. Atkinson, Y . Girard, J. Rokach, C. S. Rooney, C. S. McFarlane, A. Rackham, and N. N. Share,
J. Med. Chem., 1979, 22, 99.

4 8 K. Sato, H. Adachi, T. Iwaki, and M. Ohashi, J. Chem. SOC., Perkin Trans. 1, 1979, 1806.
49 C. Deshayes and S . Gelin, J. Heterocycl. Chem., 1979,16,657.
50
S. Gelin, C. Deshayes, and M. Chabannet, J. Heterocycl. Chem., 1979,16, 1117.
5 1 F. Eiden and E. G. Teupe, Arch. Pharm. (Weinheim, Ger.), 1979,312,591.
’* J. H. Looker, D. L. Shaneyfelt, and W. Halfar, J. Heterocycl. Chem., 1979, 16, 1281.
” R. H. Kuroyan, A. I. Markosyan, and S. A. Vartanyan, Arm. Khim. Zh., 1979, 32, 801.
Ph Me
P h o
CH=CMe, Et0,C R2
R 0
(54) R = 0 (56) (58) R' = H, R2 = Me
(57) (59) R' = Me, R2 = H
(55) R = NNHPh
PhN-NH
PhN\ \ C O , E t
R3 R4 C0,Et
(62) R3R4 = 0 (63)
(60) (61) (64) R3 = H, R4 = Ac
A number of biologically important 4-pyrones have been studied; for example,

stegobinone (66),the pheromone of the drugstore beetle (Stegobium paniceurn),
has been synthesizeds4" by cyclization of the triketone ( 6 5 ) with LiNPri by a
biomimetic synthesis from the same precursor.54b An antifungal antibiotic,
phacidin, has been isolated from a fungus and shown to be 2-methoxy-6-
Meo
nonanoyl-4-oxo-4H-pyran-3-carboxaldehyde.55 X-Ray crystallography has
shown that crispatone, a major secondary metabolite of a mollusc, Tridachia
crispata, has the structure shown in (67).56
(EtCCHMe),CO
II
0
+ MeCHO -LiNPr; Me
0
CHMeCEt
Me
It
0
(65)
(66)
Pyrylium Salts.-Acetylation of isoparaffins, such as (68), under Friedel-Crafts

conditions at low temperatures produces pyrylium salts (69). The ratio of
reactants and the presence or absence of chloroform as a solvent affect the yield
of the mixture of isomers which is often obtained, through the intermediacy of a
carbenium ion. The pyrylium salts were converted into pyridines (70) by aqueous
a m m ~ n i a . ~However,
' 3-methylpentane gave only 3-ethyl-2,4,6-triinethyl-
pyridine.
54 ( a ) J. M. Ansell, A. Hassner, and W. E. Burkholder, Tetrahedron Lett., 1979, 2497; (6) M.
Sakakibara and K. Mori, ibid., p. 2401.
5 5 G. A. Poulton, T. D. Cyr, and E. E. McMullan, Can. J. Chem., 1979, 57, 1451.
56 C. Ireland, D. J. Faulkner, J. S. Finer, and J. Clardy, J. A m . Chem. SOC.,1979, 101, 1275.
'' M. Arnaud, A . Pedra, C. Roussel, and J. Metzger, J. Org. Chem., 1979, 44, 2972.
(71) (704 ( 7 0 ~
Pyrylium salts undergo some interesting reactions; for example, addition of
methoxide ion, which may occur at C-2 or C-4, according to the structure of the
The rates of some of these reactions in buffers have been measured
spectrophotometrically and the behaviour of the salts has been explained in
electronic and structural terms.59 2,6-Diphenylpyrylium perchlorate reacts with
tributyl phosphite (by an Arbuzov rearrangement) to give a high yield of the
phosphite (71).60
Applications of di- and tri-phenylpyrylium salts continue to be exploited in the
synthesis of pyridines, thiocarbonates, thiocyanates,61" nitriles,61b and NN'-
diaryl-carbodi-imides.61' Conversion of pyrylium salts into 2-acyl-furans and
2-pyrones by sulphuric acid is dependent on the concentration of the acid.61d
3 Heterocycles containing One Sulphur Atom

Reduced Thiopyrans.-The tetrahydrothiopyran-3,5-dione(73)has been syn-
thesized by treatment of the keto-diester (72)with butoxide, and it is cyclized
by barium hydroxide to the furothiopyrone (74), which is a potential synthon for
natural furans. Partial reduction of the dione (73)and dehydration gave the
dihydrothiopyrone (75).62
0 Q0A CN CN
R'
(y? R2
(CH2120Ac (77)
(75)
58 A. R. Katritzky, R. T. C. Brownlee, and G . Musumarra, Heterocycles, 1979, 12, 775.
59 G. Doddi, S. Fornarini, G . Iluminati, and F. Stegel, J. Org. Chem., 1979, 44, 4496.
6o V. I. Boev and A. V. Dombrovskii, Zh. Obshch. Khim., 1980, 5 0 , 4 6 7 .
61 ( a ) A. R. Katritzky, U. Gruntz, N. Mongelli, and M. C. Rezende, J. Chem. Soc., Perkin Trans. 1,
1979, 1953; ( 6 )A. R. Katritzkyand P. Molina-Buendia, ibid., p. 1957; ( c )A. R. Katritzky, P. L. Nie,
A. Dondoni, and D . Tassi, ibid., p. 1961; ( d )J. W. Pavlik and A. P. Spada, Tetrahedron Lett., 1979,
444 1
62 S. Bernasconi, C. Capellini, A. Corbella, M. Ferrari, P. Gariboldi, G . Jommi, and M. Sisti, Gazz.
Chim. Ital., 1979, 109, 5 .
Acrolein has been cyclized, in excellent yield, with hydrogen sulphide and
copper in triethylamine, at -10 "C, to 5,6-dihydro-2H-thiopyran-3-carboxalde-
hyde, whose oxime has a slightly sweet taste.63 When sulphonyl diacetonitrile
(76) reacts with @-unsaturated ketones under basic conditions, 3,4-dihydro-
2H-thiopyran-2-carboxamides(77; R1,R2 = Me or Ph) are obtained in moder-
ate yields.64
The conformation of 5,6-dihydro-2,6-diphenyl-2H-thiopyran has been shown
by n.m.r. spectroscopy at 270 MHz to be h a l f - ~ h a i r Reduction
.~~ of trans-2,6-
diphenyl-cis- 3-methyltetrahydrothiopyran-4-oneswith either LiA1H4or LiOPr'
gave exclusively the equatorial alcohols.662-Vinylthian is oxidized, in 80% yield,
by periodate to the l-oxide (78),which was converted into the 2-methyl derivative
(79) by BuLi and MeI; reduction of this by NaBH4 and methyl triflate gave the
tetrahydrothipyran (80) in 75% yield. The hexafluorophosphate of (80) under-
went ring-expansion under the influence of a base to form the thiacyclonon-4-ene
(81 y 7Photochemical oxidation of tetrahydrothiopyran in oxygen gave a quanti-
tative yield of the l-oxide.68
(78) R = H
(79) R = Me
P h G :0
phoph
maleic anhydride
- AH
Ph
(84)
CPh
Ph<l
styrenh
PhQ Ph
Thermolysis of the 3,4-dihydro-2H-thiopyran (82) in the presence of

dienophiles such as maleic anhydride, styrene, and norbornene gave adducts such
as (84)and (85). The thiochalcone (83) is assumed to be an intermediate.69The
ylide (87), prepared from methyl 6-vinylthian-2-carboxylate (86) and methyl
fluorosulphonate, undergoes a 2,3-sigmatropic ring-expansion to methyl
1-(methylthio)cyclohept-3-enecarboxylate(88);the cyclopentane (89) is formed
as a by-product."
63 B. Unterhalt and M. Ghori, Z. Lebensm.Unters. Forsch., 1980,170, 34.

64 D. A . Crombie, J. R. Kiely, and C. J. Ryan, J. Heterocycl. Chem., 1979, 16, 381.
'' P. M. Henricks and C. H. Chen, J. Org. Chem., 1979,44, 3591.
66 N. Satyamurthy and K. Ramalingam, Indian J. Chem., Sect. B,1979, 17, 62.
67 V. Cere, C. Paolucci, S. Pollicino, E. Sandri, and A. Fava, J. Org. Chem., 1979, 44, 4128.
6 R T. Tezuka, H. Miyazaki, and H . Suzuki, Tetrahedron Lett., 1978, 1959.
69 T. Karakasa and S. Motoki, J. Org. Chem., 1979, 44,4151.
70 E. Vedijs, M. J. Arnost, and J. P. Hagan, J. Org. Chem., 1979, 44, 3230.

,:'F"\"~E -"
56 C02Me +0 0
SMe
2 ~ +b
'
CH=CH,
s M e
.=;
H2C /
C0,Me
186) E C02Me
= (87) (88) (89)
Horse-liver alcohol dehydrogenase reduced racemic tetrahydrothiopyran-4-
ones stereospecifically to a mixture of the cis- and the trans-alcohols (92). The
@
Ph Ph 20:
synthesis of several of the ketones (91; R1 = Me, Et, Pr', or Ph) from tetra-
hydrothiopyran-4-one ethylene ketal (90) has been d e ~ c r i b e d . ~ '
8
-
RQR'
2 R3
Y'
0 0 (95)
(90) R1 = H,R2R3 = OCH2CH2O (94)
(91) R2R3 = 0 (93)
(92) R2 = H , R 3 = OH
Thiopyrans.-Diethynyl ketones, e.g. (93), have been treated with SCI2 to give
moderately good yields of thiopyran-4-ones (94).72A new method of preparing
symmetrical dimeric thiopyrans [such as (SS)]consists of heating 2,6-diphenyl-
pyrylium perchlorate with a catalytic amount of Ph,P in pyridine. The scope of
this reaction has been studied; some pyrans and benzopyrans also gave dimers
under these c o n d i t i o n ~ The
. ~ ~ 3,6-dihydro-2H-thiopyran-3-one (97) has been
synthesized by cyclization of methyl acetonylthioacetate (96) with base, followed
by methylation and reduction to give the thiopyran (97) together with a small
amount of 3,4-dihydr0-2H-thiopyran-3-0ne.~~
Radical bromination of 6-methyl-4-methoxy-2H-thiopyran-2-one with NBS
gave the 6-CH2Br and 6-CHBr2 derivatives. Additional bromination in the ring
was also possible with Br, plus A c O H . ~ 'The kinetics of the thermal rearrange-
ment of thiabenzenes to 2- and 4-thiapyrans have been investigated for S-alkyl
and S-aryl derivatives. Evidence emerged that an intramolecular rearrangement
of the S-aryl group in a 1,2- or 1,4-migration o c c ~ r r e d . ~The
' dihydrothiopyran
(98), which was prepared from hexa-2,4-diene and fluorene-9-thione, has been
oxidized to the sulphoxide with NaI04. Heating the sulphoxide in A c 2 0 con-
verted it into the spirothiopyran (99) in a vinylogous Pummerer r e a ~ t i o n . ' ~
7' J . Davies and J. B . Jones, J. A m . Chem. Soc., 1979,101, 5405.

72 N. M. Morlyan, E. L. Abagyan, and S. 0. Badanyan, Arm. Khim. Zh., 1979,32,318
73 G. A . Reynolds, C. H. Chen, and J. A. Van Allan, J. Org. Chem., 1979,44,4456.
74 K. Skinnernoen and K. Undheim, Acta Chem. Scand., Ser. B, 1979,33, 767.
75 0. Caputo, L. Cattel, and F. Viola, Farmaco, Ed. Sci.,1979, 34, 869.
76 H. Pirelahi and H. Haghgooii, J. Heterocycl. Chem., 1979, 16, 917.
77 K. Praefcke and C . Weichsel, Liehigs Ann. Chem., 1979, 784.
2,6-Diphenyl-4-oxothiopyran-3-carboxaldehyde (100) was produced in high
yield by an unusual oxidation of 4-chloro-2,6-diphenyl-2H-thiopyran-3-
carboxaldehyde by S e 0 2 as well as from the hydroxymethylene compound
(Scheme 1).Numerous potentially useful conversions of reduced thiopyrans and
thiopyrans have been described.78
Reagents: i, SeO,; ii, AcOH

Scheme 1
4 Fused Heterocycles containing One Oxygen or Sulphur Atom
Chromans.-When triketones such as (101; R' = H , R 2 = Ph) or [101; R'R2 =
(CH2)J were catalytically hydrogenated over Raney nickel in alkali at 50 "C,
partial reduction and simultaneous cyclization occurred, t o give high yields of the
chroman-5-ones (102), but when rhodium-carbon was used, at 80-100 "C,the
chroman (103) was ~ b t a i n e d . 'Treatment
~ of coumarins, e.g. (104), with B2H6
plus NaOH and then with H 2 0 2yielded the chroman-3-01s (105). A mixture of
cis- and truns-chroman-3,4-diols was obtained when 3-hydroxycoumarin was
treated similarly.80 The post-coital antifertility drug (107), labelled with I4C at
C-2, has been synthesized from PhCH214C02Hand the ketone (106).81A simple
~ C H , C H R ~ C R ~
0 II
n
v
R3
(102) R3 = 0
(101)
(103) R3 = H2
(104) (105) Ph
--+
C6H40H-p
(106)
(107)
78 C. C. Chen and G. A. Reynolds, J. Org. Chem., 1979,443144.
79 V. G. Kharchenko, N. S. Srnirnova, L. I. Markova, G. I. Rybina, and K. M. Korshunova, Zh. Org.
Xhim.,1979, 15, 1961.
*" S. Kirkiacharian, J. D. Brion, and P. Reynaud, C.R.Hebd. Seances Acad. Sci., Ser. C,1979,289,227.
P. L. Kole and S. Ray, J. Labelled Compd. Radiopharm., 1979, 16, 373.
(111) (1 12)
homologue (110) of a-tocopherol has been synthesized from quinol dimethyl
ether (108) and the cyclic acetal (109) of known stereochemistry.82Addition of
cyclohexanone to o-cinnamoylbenzoic acid gave the spirochroman (111), which
was dehydrated to the unsaturated spiran (112).83
(-)-A'-Tetrahydrocannabinol (115) has been synthesized from p-menth-2-
ene-1,s-diol (113) and olivetol (114), using one of several catalysts (BF,.Et20,
TsOH, ZnC12, ZnBr2, ion-exchange resin, or SnCl,) and solvents (CH2C1,, PhH,
or E t 2 0 ) . Of these, ZnC1, and CH2C12gave the best results in terms of yield and
exclusion of by-products. The diol(l13) is preferable to p-mentha-2,8-dien-l-o1
as its use leads to fewer by-product^.'^
Me
CMe,OH (114)
(113) (115)
The n.m.r. spectra of a number of 2-substituted 4-chromanols and l-thio-4-

chromanols in DMSO show that the OH proton resonates at higher field when
it is pseudo-axial than when pseudo-equatorial; its coupling constant with C H is
lower in the pseudo-axial than in the pseudo-equatorial position. The observa-
tions may be explained in terms of conformational equilibria of the C - 0 bond.85
Dianin's compound (116; R' = R2 = Me, R3 = OH) forms clathrates with
small molecules; the hour-glass-shaped cavity is changed into one which lacks
the central constriction by omitting one of the 2-methyl groups, as in (116;
R' = H , R2 = Me, R3 = OH), but when R1 is methyl and R2 = H, the com-
pound does not form clathrates. Crystallographic measurements support these
R. Barner and M. Schmid, Helu. Chim. Acta, 1979, 62, 2384.

83 L. N. Doushak, V. A. Kaminskii, and M. N. Tilichencho, Zh. Org. Khim., 1979, 15, 1558.
84 G. R. Handrick, D. B. Wiss, H . C. Dalzell, and R. K. Razdan, Tetrahedron Lett., 1979, 681.
85 K. Hanaya, H . Kudo, K. Gohke, and S. Imaizumi, Bull. Chem. SOC.Jpn., 1979,52,2163.
findings and provide details of the conformation of the pyran ring.86 The
measurements also show that formation of clathrates depends on the formation
of hydrogen bonds between six molecules of Dianin’s compound. Replacement
of the 4’-hydroxy-group by other functions (e.g. NH2 or SH) has an effect on the
compound’s ability to form clathrates. The thiol forms 3 : 1clathrates with carbon
tetrachloride, bromotrichloromethane, and l,l,l-tri~hloroethane.~~
A Mannich reaction on 2,2-dimethylnaphtho[ 1,2-b]pyran-6-01 ( 1 17) gave the
5-aminomethyl derivative. Catalytic reduction of this gave the 5-methyl com-
pound. In an attempt to chloromethylate the chroman (117), the spiran (118)
was obtained in 78% yield.88
&
q
OH
HCHO, H
(223 0 0
(118) ‘
Reduced benzo[1,2-b:5,4-b‘]dipyrans such as (119), when treated with 3-
chloroperbenzoic acid at 15-20 “ C , give macrocyclic lactones (120).g9
Tocopherols and the mechanism of their anti-oxidant properties continue to
interest chemists. Potassium superoxide, in the presence of dicyclohexyl-18-
crown-6, converts the model compound 2,2,5,7,8-pentamethylchroman-6-01
(121) into its 4a,5:7,8-diepoxide (l22).” Benzoyl peroxide and the peroxides
which are present in sunflower oil oxidize a-tocopherol to the phenoxyl radical,
according to evidence obtained by e.s.r. and i.r. s p e c t r ~ s c o p yIn
. ~another
~ study,
(+)-&tocopherol was oxidized, above 180 “C, in various fats to the dimers (123)
and (124). The effects of temperature and the nature of the triglyceride on the
relative amounts of the two dimers were
86 J . H. Gall, A. D. U. Hardy, J. J. McKendrick, and D. D. MacNicol, J. Chem. SOC.,Perkin Trans. 2,

1979,376.
’’ A. D. U. Hardy, J. J. McKendrick, D. D. MacNicol, and D. R. Wilson, J. Chem. Suc., Perkin Trans.2,
1979,729.
K. Maruyama, T. Tobimatsu, and Y. Naruta, Bull. Chem. SOC. Jpn., 1979, 52, 1143.
89 B. Graffe, M. C. Sacquet, and P. Maitte, Bull. SOC.Chim. Fr., Part2, 1979, 350.
90
M. Matsuo, S. Matsumoto, Y. Iitaka, A. Hanaki, and T. Ozawa, J. Chem. SOC., Chem. Commun.,
1979.105.
” V. G. Parteshko, A. G . Staren’kii, and V. G. Koshechko, Dokl. Akad. Nauk SSSR, 1979,245,855.
92 T. Fujitani and H. Ando, Yukagaku, 1 9 7 9 , 2 8 , 8 9 6 .
A g.1.c.-m.s. method (which may be of interest to organic chemists) has been

described for quantitatively estimating amounts of 1-50 ng cm--3of canna-
binoids in blood and urine.93
H o
Me
a
(123) X
(124) X
=
=
M
bond
0
Re
Me0 \
m:;?(126)
R = [(CH&CHMeI3Me
2H-Chromenes.-Several new methods of synthesizing 2H-chromenes have
been described. Substituted ortho-allylated phenols have been cyclized, at 30 "C,
with N-iodosuccinimide, to the corresponding 3-iodo-chromans; these are dehy-
droiodinated in high yield, to the 2,2-dialkyl-~hromene Good. ~ ~ yields of 2H-
chromenes have also been obtained from ortho-allylated phenols by using either
Adogen 464 and dichromate in benzene or DDQ.95 When 3-(propargyl-
oxy)phenyl benzoate was heated in NN-diethylaniline, it rearranged to 5-
benzoyloxy-2H-chromene in good yield, but 3 -(propargyloxy)anisole gave a
mixture of 5- and 7-methoxy-2H-chromene in approximately equal propor-
tion~.~~
Precocene I1 (125) and other chromenes have been synthesized and screened
for their effect on the cloth moth. Precocene I1 has larvicidal proper tie^.^^ A
trifluoro-compound (126), related to precocene, has been synthesized9' from
3,4-dimethoxyphenol, trifluoroacetone, and allylmagnesium bromide. Several
natural chromenes, for example 6-acetyl-2,2-dimethyl-5-hydroxy-8-methoxy-
2H-chromene, have been synthesized from the appropriate substituted 2-
hydroxyacetophenone and either 2-methylbut-3-en-2-01 or 3-chloro-3-
methylbut- l - ~ n e 2H-Chromenes
.~~ are rarely prepared from chromanones, but
a direct conversion of substituted 2,2-dimethylchromanones, e.g. (127), in high
yield, into 2H-chromenes, e.g. (128), has been achieved by the action of PC15.100
93 M. E. Wall and D. R. Brine, Ado. Biosci., 1978,22, 315.

94 A. Bongini, G. Cardillo, M. Orena, G. Porzi, and S. Sandri, Tetrahedron Lett., 1979, 2545.
9s G. Cardillo, M. Orena, G. Porzi, and S. Sandri, J. Chem. SOC., Chem. Commun., 1979, 836.
96 V. G. S. Box, B. A. Burke, and C. Melaw, Heterocycles, 1979, 12, 451.
97 D. J. Gale and J. F. K. Wilshire, J. Texf.Inst., 1979, 70, 525.
98 F. Camps, J. Coll, A. Messeguer, and M. A. Pericas, J. Heterocycl. Chem., 1980, 17, 207.
99 A. C. Jain, R. Khazanchi, and A. Kumar, Bull. Chem. SOC.Jpn., 1979, 52, 1203.
loo F. Camps, J. Coll, A. Messeguer, and M. A. Pericas, Tetrahedron Lett., 1979, 3901.
Substituted 2-iminochromenes (130), which have anti-tumour properties, have

been synthesized from the salicylaldehydes (129) and N-substituted cyano-
acetamides.'"
Many 2,2-dimethylchromenes (131) are oxidized (in 32-77% yield) by
Tl(N03)*in MeOH to the dihydrobenzofurans (132).'02 The naturally occurring
compound precocene I (133) gave the epoxide (134) upon treatment with NBS
and NaH. The epoxide is readily cleaved, and may have a role in the termination
of the production of juvenile hormone in some insects.lo3 The ease with which
the double-bond of the pyran is reduced in 4-aryl-2H-chromenes varies accord-
ing to whether the 4-aryl group also has a nitro-group, because the amine that is
RLm It-w
then formed increases the pH of the medium. This effect can be offset by
(131) R
(133) R
\
=
=
/
H, OMe, or CHO
7-OMe
\
(132)
CH(OMe)2
M e o
(134)
q
H O a A r , H O G
Ar
\
CI -
0 (136) (137)
(135) Ar = 3-Me0-4-OH-C6H3
adjustment of the P H . " ~ Bromination of lapachone (135) with NBS gave the
4-bromo-derivative. Its halogen is reactive and is easily replaced by OH, OMe,
OEt, and OAc on boiling with water, methanol, ethanol, and silver acetate,
respectively. Dehydrobromination with pyridine led to natural dehydro-cu-
lapachone; oxidation with M n 0 2 gave the 4-chromanone, which is the first
synthesis of this natural compound.'05 The effect of salts on the equilibrium
between pyrylium salts (136) and their chalcones (137) in water at pH 3 - 4 has
been examined by U.V. spectroscopy and by polarography. At constant pH, the
concentration of the salt (136) increased as that of sodium perchlorate
increased. O6
4H-Chromenes.-A new route to 4H-chromenes (139) employs the reaction of
o- (acy1oxy)benzyl bromides (138) with phosphoranes, and usually gives very
good yields.lo7When 2H-chromene is treated with NaH or Bu'OK, it is partially
lo' C. N. O'Callaghan and M. L. Conalty, Proc. R. Ir. Acad., Sect. B,1979, 79, 87.
lo* S. Antus, A. Gottsegen, M. Nogradi, and A. Gergely, Chem. Ber., 1979, 112, 3879.
lo' R. C. Jennings and A. P. Outtridge, J. Chem. SOC.,Chem. Commun., 1979,920.
*04 P. K. Arora, P. L. Kole, and S. Ray, Indian J. Chem., Sect. B, 1979,18, 199.
lo' R. B. Gupta and R. N. Khanna, Indian J. Chem., Sect. B,1979, 18, 16.
H. Ohta, H. Watanabe, R. Yamaguchi, and Y. Osajima, Nippon Shokuhin Kogyo Gakkaishi, 1979,
26, 116.
lo7 A. Hercouet and M. Le Corre, Tetrahedron Lett., 1979, 2995.
oocR
0
II
+ Ph,P=CHCO,Me __+
CH,Br [95%]
(138) (139)
isomerized to 4H-chromene. Base-catalysed 'H-,H exchange in 2H-chromene
occurs at C-2 and C-4, but 2H-thiochroman is resistant to isomerization and is
deuteriated at C-2.'"
Isochromenes.-3-Substituted isochromenes (141; R = H, Me, or Ph) have been
synthesized by a new route from the dibromide (140) in good yields (Scheme
2).lo9Thermolysis of the sulphone (142) produced the isochromenes (143).110
Reagents: i, PPh,; ii, RC0,Na

Scheme 2
PhS CO(CH,),CH=CH,
SPh
(142) (143)
3-Chromanones.-A new two-stage synthesis of these rather elusive compounds
(145) employs the oxiran (144) and phenol; the first stage is catalysed by
BF,.Et,O, and cyclization is brought about by PPA."' When 3-chromanone was
treated with various alkyl halides or sulphates in the presence of Et,N' Br-, at
20 "C, a mixture of products was obtained.Il2
4-Chromanones.-Cyclization involving one of the hydroxy-groups of 2,4- or

2,7-dihydroxynaphthalene has been effected with 3-methylacrylic acid, P0Cl3,
and ZnC1, to give naphtho[2,1-b]pyran-l-ones(146) or (147).", Several sub-
108
E. A. Karakhanov, L. N. Borodina, N. V. Gruzdev, and E. A. Runova, Vestn. Mosk. Univ., Ser. 2:
Khim., 1979, 20, 577.
109
B. Begasse, A. Hercouet, and M. Le Corre, Tetrahedron Lett., 1979, 2149.
I10
W. Oppolzer, D. A. Roberts, and T. G. C. Bird, Helv. Chim. Actu, 1979, 62, 2017.
111
0. N. Bubel and I. G. Tishchenko, Khim. Geterotsikl. Soedin., 1979, 1036.
112
E. A. Runova, L. N. Borodina, A. K. Shcherbakov, and E. A. Karakhanov, Vestn. Mosk. Univ., Ser.
2: Khim., 1979, 20, 581.
113
I. Dragota and I. Niculescu. Rec. Roum. Chim., 1979, 24, 59.
&
R e o H + R q I I h
R2 CCH ,OPh
I1 0
0
\ R'
/ (148) (149)
(146) R' = OH, R2 = H
(147) R' = H, R2 = OH
stituted 2'-hydroxy-2-phenoxyacetophenones (148; R = OH or OMe) have
been converted into chromanones (149) by a Claisen condensation with methyl
formate, catalysed by ButONa.'14 Enolates of o-hydroxy-acetophenones react
with ketones at -40 "Cto give high yields of crossed aldols; these undergo facile
dehydration to 2,2-dialkyl-chromanones.'15
Chromanones, e.g. (150), react with formaldehyde (3 mol ratio) in an acetic
acid-benzene mixture containing concentrated H2S04 to form a spiro-
compound, e.g. (151), in up to 70% yield, but, when the molar ratio of aldehyde
is one, a small amount of the 3,3-di(acetoxymethyl)chromanoneis usually
formed. Bromination of the chromanone (150) gave rather low yields of one of
two isomers (152)and (153),according to whether acetic acid was present or not.
Measurements of the rate of exchange of deuterium in the chromanone (150),
using n.rn.r. spectroscopy, suggested that the methylene protons attached to C-3
are the most reactive.'16
(150) R' = R2 = H (154)

(152) R1 = Br, R2 = H
(153) R' = H, R2 = Br 1
(157) (158) (156) R = H

Expansion of the pyrone ring of chromanones has been achieved by reaction
with ethyl diazoacetate and BuLi at -78°C [to produce the a-diazo-ester (154)]
followed by acid-catalysed conversion, at room temperature, into the benzoxepin
(155). De-ethoxycarbonylation led to the parent 2,3-dihydro-l-benzoxepin-4-
(5H)-one (156). By a similar sequence, isochroman-4-one (157) was converted
into the hitherto unknown 1,5-dihydro-2-benzoxepin-4(3H)-one(158)."'
V. Szabo and A. Kiss, Magy. Kern. Foly., 1979,85, 353.
A. Banerji and N. C . Goomer, Tetrahedron Left.,1979, 3685.
A. Ninagawa, R. Nomura, and H. Matsuda, Bull. Chem. SOC.Jpn., 1979, 52, 1169.
11' R. Pellicciari, B. Natalini, M. Taddei, A. Ricci, G. A. Bistocchi, and G . D e Meo, J. Chem. Res. ( S ) ,
1979,142.
Another seven-membered ring was obtained from a chromanone (159) by
subjecting it to a Schmidt reaction which gave a 1,4-benzoxazepine (160).'18
0-Benzylation of 3-(3-hydroxy-4-methoxybenzylidene)chromanone (161) pro-
ceeded normally at 100 "C or below, but at 153 "C the exocyclic double-bond
migrated into the pyrone ring to give the chromone (162). Also formed as a minor
product was the flavone (163). Further experiments showed that the rearrange-
ments occurred in DMF-K2C03 without benzyl chloride, and a mechanism has
RZ
+
NH
R' 0
(159) (160)
R'=H, Me, or Et; R2 = H, C1, or OMe
C0,Et
I
CH2CNHMe
CAr II
H 0
0
&
(161) Ar = 3-OH-4-MeOC6H3 (164)
HMe
0 \ /
(162) R' = H, R2 = 3-PhCH20-4-MeOC6H3
(163) R' = 3-OH-4-MeOC6H3,R2 = H (165)
Chromones.-2-Hydroxychromanones, such as (149), have been dehydrated to

chromones by means of HCl in EtOH.l14 When malonamates such as (164) are
heated with 2-naphthol and POC13, 2-aminonaphtho[2,1-b]pyrans (165) are
obtained.'" The formation of a chromone (Simonis reaction) or a coumarin
(Pechmann reaction) by cyclization of a phenol with ethyl acetoacetate12' in the
presence of a catalyst has been studied on lY4-dihydroxynaphthalene.Sulphuric
acid, HC1 in EtOH, and heating without a catalyst gave respectively the coumarin,
the coumarin, and the chromone.122 3,4-Dichloro-2H-chromen-2-ol (166)
(prepared by reduction of the corresponding coumarin with lithium tri-t-
butoxyaluminium hydride), when heated with mineral acid, gave 3-chloro-
chromone (167; X = Cl).123Another new route to 3-halogenochromones is the
reaction of o-hydroxyacetophenone with the dimethyl acetal of DMF to give the
'18 D . R. Shridhar, C. R. Sarma, R. R. Krishna, and Y. P. Sachdeva, Indian J. Chem., Sect. B, 1979,17,
155.
'19 D . Mulvagh, M. J. Meegan, and D . Donnelly, J. Chem. Res., 1979. ( S ) , 137; ( M ) ,1713.
A . Balbi, M. Di Braccio, G. Roma, A . Ermili, A . Ambrossini, and N. Passerini, Farmaco, Ed. Sci.,
1979,34, 595.
lZ1 G. P. Ellis, 'Chromenes, Chromanones and Chromones', John Wiley, New York, 1977, p. 526.
lZ2 J. H. Pardanani, Y. G. Gackwad, and S. Sethna, J. Indian Chem. SOC.,1979,56, 644.
lZ3 M. K. Rastogi, C. Kamla, R. P. Kapoor, and C. P. Garg, Indian J. Chem., Sect. B, 1979, 17, 34.
enamine (168), which has been treated with iodine, bromine, or t-butyl hypo-
chlorite to give the 3-halogenochromone (167).'24
Bis-chromones of the type (169) and related compounds have been synthesized
from h y d r o ~ y - s t i l b e n e s . ' ~ ~
The 13C n.m.r. spectra of some benzopyranones12hand the mass spectra of
simple alkyl-chromones and their deuteriated derivative^'^' have been investi-
gated. Ph Ph
H \
0 0 0
(169)
(170)
Chromone-3-carboxaldehyde reacts with diphenylketen to give the
pyranopyran (170)'*' and with primary arylamines to form (aryl-
iminomethyl)chromones, which react with a nucleophile by addition rather than
by conventional ring-cleavage. The stabilizing effect of hydrogen-bonding on the
tautomerism (Scheme 3) is believed to account for this change in character. A
second molecule of amine reacts readily with the anil to give the compound shown
in Scheme 3. Alcohols and thiols also add to 3-(aryliminomethyl)chromone,
which is oxidized by M n 0 2 to the chroman-2,4-dione (171).12yaWhen the
3-aldehyde or the 3-carboxylic acid is treated with red fuming H N 0 3 in H2S04,
5-nitrobenzofuran-2,3-dione2-oxime is formed.'296 The latter was synthesized
independently from 2,5'-dinitro-2'- hydroxyacetophenone.
CHNHAr
Scheme 3
Although chromone-3-carboxaldehyde is readily prepared, the 2-isomer is
much less readily available. Selective reduction of methyl chromone-2-carbox-
ylate with NaBH, and MeOH has given the 2-hydroxymethyl compound,
apparently without affecting the carbonyl group of the pyrone; oxidation with
R. B. Gammill, Synthesis, 1979, 901.
F. Eiden and C. Schmiz, Arch. Pharm. (Weinheim, Ger.), 1980, 313, 120.
T. N. Huckerley and G. Sunman, J. Mol. Struct., 1979, 56, 87.
12' S . Eguchi, Org. Mass Spectrum., 1979,14, 345.
12' F. Eiden and I. Breugst, Chem. Ber., 1979, 112, 1791.
12' ( a )A. 0.Fitton, J. R. Frost, P. G. Houghton, and H. Suschitzky, J. Chem. Soc., Perkin Trans. I , 1979,
1691; ( b ) W. V. Curran, F. M. Lovell, and N. A. Perkinson, Tetrahedron Lett., 1979, 2221.
3 02 Heterocyclic Chemistry
MnO, converted this compound into the 2-aldehyde in about 30% overall
yield.'3o When 3-brornochromone (167; X = Br) is treated briefly with either a
1,3-diketone or a 3-0x0-ester in the presence of 1,5-diazabicyclo[4.3.0]non-5-
ene, the pyrone ring is cleaved and a trisubstituted furan (172) is formed, in high
yield.' 31
Chromone-3-carbonitrile reacted with various hydrazines and reactive methyl-
ene compounds to form benzopyrano[4,3-~]pyrazolesor 4-(2-hydroxybenzoyl)-
1-phenylpyrazoles and benzopyran0[2,3-b]pyridines."~ Preferential electro-
philic attack at C-5 of 6-substituted chromones (and cournarins) has been
demonstrated again by a Fischer indolization of ethyl 6-hydrazinochromone-2-
carboxylate (173) to give (174) in good yield.'33
Some derivatives of 4H-naphtho[l,2-bJpyran-4-one(7,8-benzochromone)

inhibit oxidases which are concerned in carcinogenesis by polycyclic hydro-
carbons. Structure-activity relationships for many compounds of this type have
been i n ~ e s t i g a t e d . ' ~ ~
Thiochromans and Thiochromones.-The spirothiochroman (175) has been
synthesized from 3-methylene-lH-2-benzothiopyran-4(3H)-one(176) and its
stereochemistry has been examined, using X-ray crystallography. 135
Modifications which have been made to Dianin's compound (see also under
C h r o m a n ~ ~ ~ *include
*') replacement of the ring oxygen by sulphur. Some such
compounds retain the clathrate-forming ability of the original molecule. 136
(175)
0 2
(177) R = H
(179) R = OAc (178)
'31 M. Payard and J . Couquelet, Synthesis, 1979, 889.
13' R. B. Gammill, J. Org. Chem., 1979, 44, 3988.
132
C. Ghoss, D. K. SinhaRoya, and K. K. Mukhopadhyay, J. Chem. SOC.,Perkin Trans. 1, 1979, 1964.
M. A, Khan and M. L. de B. Morley, .I Heterocycl.
. Chem., 1979,16, 997.
134 S. Nesnow, J. Med. Chem., 1979, 22, 1244.
13' 0. H. Johansen, T. Ottersen, and K . Undheim, Actu Chem. Scand., Ser. B, 1979, 33, 669.
136 A. D. U. Hardy, J. J. McKendrick, and D. D. MacNicol, J. Chem. Soc., Perkin Trans. 2, 1979, 1072.
Thiochroman (177) reacts with diethyl diazomalonate, with copper bronze as a
catalyst, to form the sulphonium ylide (178) in high yield. Solvolysis of this in
acetic acid gave 2-acetoxythiochroman (179) and thi0chr0man.l~~
Photoaddition of thiochromone 1,l-dioxide in the presence of benzene, for
example, gave a 2 : 1 adduct (180) in 32% yield. A correlation was observed
between the behaviour of the benzenoid compounds and their ionization poten-
~ ~ ~ esters of thiophen-2-thiolocarboxylic acids undergo a
t i a l ~ . ' S-Aryl
phytochemical transformation into a mixture of products, including the
thienobenzothiopyranones (Scheme 4).'38b
Scheme 4
Flavans.-The presence or absence of a 6'-substituent in chalcone epoxides plays
an important part in the course of the reaction which leads to a flavanol only for
6'-unsubstituted epoxides.139 Reduction of 2'-(benzyloxy)chalcone epoxides
(181) with LiAlH, and AICI, led to flavan-2,3-trans-3,4-cis-diols or the
2,3 -truns-3,4-trans-diols, depending on the substitution pattern of the benzene
ring adjacent to the carbonyl group.'4o
a:::cHph
+ WPh 0
II
(181)
0
\ 1
OH
OH
Isoflavans and Isoflavylium Salts.-Cycloaddition of dimethylsulphoxonium

methylide (183) to cyclohexanediones (or their enols) (182) gave good yields
of 3,4,5,6,7,8-hexahydro-3-hydroxy-2H-l-benzopyran-5-ones (184). When the
O-acetate (185) of this was pyrolysed at 150 OC, a 2 : 1mixture of 2 H - (186) and
4H-benzopyrans (187) was obtained.141
Isoflavylium perchlorates (188) are converted (in high yields) into 2-aryl-
benzofurans when treated with Pr'OH, HCI, and H202.The mechanism shown
y-JAr + Me,SO
I1 - yJ0R - { O
( 1 Pp h
iOPh
CH2
I1 Ar
0 0 (183) 0
(182) (184) R = H
(185) R = Ac (187)
13' R. Pellicciari, M. Curini, P. Ceccherelli, and B. Natalini, G a z z . Chim. Zfaf.,1978, 108, 671.
( a ) I. W. J. Still and T. S . Leong, Tetrahedron Lett., 1979, 1097; ( b )K. Beelitz, G. Buchholz, and K.
Praefcke, Liebigs Ann. Chem., 1979, 2043.
139 J. A. Donnelly, M. J. Fox,and T. C . Sharma, Tetrahedron, 1979, 35, 1987.
I4O D. D. Berge and M. M. Bokadia, Zndian J. Chem., Sect. B,1979, 18, 77.
141 P. Bravo and C. Ticozzi, Gazz. Chim. Zral., 1979,109, 169.
J
Scheme 5
in Scheme 5 has been proposed, In the absence of oxidizing agent and acid, a
dimeric isoflavene is formed.142
A new type of natural isoflavan has been isolated from the roots of Abrus
precatorius. Chemical and spectral evidence supports structure (189).1 4 3 Among
several isoflavans present in Lotus hispidus is a new compound, 5,4,'-dimethoxy-
7,2'-dihydroxyisoflavan ( 5-methoxyvestitol).
R 1 - a ;
MeOQf&R: 0 0= H
(190) R2 = R3
(189) R = H or M e 0 (191) R2 = C1,R3 = H

(192) R2 = R3 = C1
F1avanones.-Most of the recent literature on flavanones concerns their natural
occurrence, but the oxidation of 4-oximinoflavan with SeO, in aqueous dioxan
has provided a means of reclaiming flavanone from its oxime; some flavone and
a little 3,3'-biflavonyl were also A method has been described for
separating flavanones and flavones, using commercial high-performance t.1.c.
plates. The R fvalues of the components varied considerably, according to the
proportion of water in the eluting 1 i q ~ i d .An
l ~ ~extensive study has been made
of the behaviour of flavanones in the mass spectr~rneter.'~'
Prenylation of 3,5,7,4'-tetrahydroxyflavanone (aromadendrin) with 2,-
methylbut-3-en-2-01gave mainly the 8-prenyl derivative, together with some of
the 6-isomer, but the reaction with 4-bromo-2-methylbut-2-ene led to the
6,g-diprenyl- together with some 7-prenyloxy- and 6 - p r e n y l - c o m p o ~ n d s . ' ~ ~
Flavanones (190) react with CuCl, to give 3-chloro- (191) or 3,3-dichloro-
flavanones (192), according to the substituents present. The dichloro-compounds
142
C. Deschamps-Vallet, J . B. Ilotse, M. Meyer-Dayan, and D. Molho, Tetrahedron Lett., 1979, 1109.
143
A. Lupi, F. Delle Monache, G. B. Marini-Bettolo, D. L. €3. Costa, and I. L. D'Albuquerque, Gazz.
Chim. Ztal., 1979, 109, 9.
144
J. L. Ingham and P. M. Dewick, Phytochemistry, 1979, 18, 1711.
145
D. D. Berge, A. V. Kale, a n d T . C. Sharma, Chem. Ind. (London),1979,282.
146
A. Hiermann, J. Chromatogr., 1979,174,478.
147
G . P. Kononenko, S. A. Popravko, B. V. Rozynov, V. G. Zaikin, and N. S. Wulfson, Bioorg. Khirn.,
1980,6, 267.
148
V. K. Gujral and S. R. Gupta, Nut. Acad. Sci. Lett., (India),1979, 2, 17.
are dehydrochlorinated by Et,N to substituted 3-ch10roflavones.~~~ An attempt
to convert cis-3-bromoflavanone into spiro[flavan-3,1’-cyclopropan]-4-one
(193) by reaction with dimethylsulphoxonium methylide gave a mixture of
several products other than the spiroflavanone, the main one being the cyclo-
propa[b]flavanone (194).lS0An almost quantitative yield of a flavone was
obtained by treatment of 5,7,4’-trimethoxyflavanonewith dimethyl sulphoxide,
a catalytic amount of iodine, and sulphuric acid, at 100°C. It is probable that
iodination at C-3 was followed by dehydroiodination. 15’ The ring-cleaving
reaction of hydrazine with flavones is well known. A similar conversion of
a
substituted 3-bromoflavanones (195) in acetic acid gave the flavone azine (196)
as the main product [together with the hydrazone (197)] at room temperature,
but in ethanol the pyrazole (198) was obtained in high yield.152
/ W P h
\ \ Me \ Br
0 0 0
(193) (194) (195)
(196) (197) (198)

Qf the many phytochemical and biological reports on flavanones, the following
are a selection of new compounds. A flavanone of unusual oxygenation pattern
has been identified in the leaves of New Zealand spinach (Tetragonia expansa).
The compound is 7,8-dimetho~yflavanone.’~~ Amongst several new prenyl-
flavonoids obtained from the roots of Marshallia grandiflora is 8-prenyl-5,7,4‘-
trihydroxyflavanone. 154
New derivatives of 5,7-dihydroxy-8-prenylflavanone have been extracted from
the aerial parts of Helichrysum hydrocephalum ; one of the gem-dimethyl groups
has been replaced by CH,OH or CHO? Flemiflavanones A (199), B, and C
are new flavanones isolated from the roots of Flemingia stricta,lS6and two new
racemic 8-benzylated flavanones (200) and (201) have been identified in the root
bark of Uuaria ~ h a m a e . ”The
~ cultivated mulberry tree, Morus afba L., is a
fruitful source of ben~opyrans;’~’a flavanone, kuwanon F (202), has recently
149 F. G. Weber and E. Birkner, Z. Chem., 1979, 19, 292.
P. Bennett, J. A. Donnelly, and M. J . Fox, J. Chem. Soc., Perkin Trans. 1, 1979, 2990.
’’’ W. Fatma, J. Iqbal, H. Ismail, K. Ishratullah, W. A . Shaida, and W. Rahman, Chem. Ind. (London),
1979,315.
N. J. Reddy and T. C. Sharma, Chem. Ind. (London), 1979,318.
M . S . Kemp, R. S. Burden, and C. Brown, Phytochemistry, 1979,18, 1765.
F. Bohlmann, C. Zdero, R. M. King, and H. Robinson, Phytochemistry, 1979, 18, 1246.
F. Bohlmann and W. R. Abraham, Phytochemistry, 1979,18,1852.
’” S. Sivarambabu, J. M. Rao, and K. V. J. Rao, Indian J. Chem., Sect. B, 1979, 17, 85.
H. N. El-Sohly, W. L. Lasswell, and C. D. Hufford, J. Nut. Prod., 1979, 42, 264.
G. P. Ellis, in ‘Heterocyclic Chemistry’, ed. H. Suschitzky and 0. Meth-Cohn (Specialist Periodical
Reports), The Royal Society of Chemistry, London, 1980, Vol. 1, p. 354.
(199) R = CH2CH=CMe2
0
(202) R = (CH2)2CH=CMe2
beer identified in the benzene extract of the root bark.159 An additional new
flavanone,16' called uvarinol(203), which has antibacterial and cytotoxic activity,
has been isolated from Uvaria chamae. 16' The antimicrobial properties of
propolis, a product obtained from bees, have been ascribed to the presence oi
pinocembrin (5,7-dihydroxyflavanone). Two tetrahydroxyflavanones have
been isolated from the stems and leaves of Inulu cappa, which grows in A ~ s a m . ' ~ ~
Amongst 2 17 flavanones, flavones, and isoflavones screened for anti-tumour
activity, a few apparently unrelated compounds showed activity.164
Isoflavanones.-In response to a fungal infection, the plant Phaseolus uulgaris
L. produces a new isoflavanoid, 8-prenyl-7,2',4'-trihydroxyisoflavanone (5-
deoxykievitone).I6'
F1avones.-A compound called skullcapflavone has been obtained from the roots
of Scutellaria baicalensis, and it was first believed to be 5,2'-dihydroxy-6,8-
dimethoxyflavone, but more recent work, in which skullcapflavone was synthe-
sized, has shown that its correct structure is 5,2'-dihydroxy-7,8-
dimethoxyflavone;'66-'h8 this is a structure that had previously been assigned to,
another natural flavone, a n d r 0 g r a ~ h i n . ISeveral
~~ other flavones were synthe-
sized during this ~ 0 r k . l ~7,8-Benzoflavones
' have been obtained in 45-65%
yields by heating ethyl benzoylacetate with 1- or 2-naphthol at 300-325 O C . ' ' '
Condensation of terephthalaldehyde with acetophenones gave the diketone
(204); on oxidation with SeO,, this gave the flavotie (205), but with H 2 0 2it gave
15Y
T. Nomura and T. Fukai, Heterocycles, 1979, 12, 943.
160
W. L. Laswell and C. D. Hufford, J. Org. Chem., 1977, 42, 1295.
161
C. D. Hufford, W. L. Laswell, K. Hirotsu, and J. Clardy, J. Org. Chem., 1979, 44,4709.
162
J . Metzger, H. Bekemeier, M. Paintz, and E. Schneidewind, Pharmazie, 1979, 34, 97.
163
N. C. Baruah, R. P. Sharma, G. Thyagarojan, W. Herz, and S. V. Gorindan, Phyrochemistry, 1979,
18, 2003.
164
J. M. Edwards, R. F. Raffauf, and P. W. LeQuesne, J. Nat. Prod., 1979, 42, 8 5 .
165
M. D. Woodward, Phytochemistry, 1979,18,2007.
166
M. Takido, K. Yesukawa, S. Matsuura, and M. Iinuma, Yakicgaku Zasshi, 1979, 99, 443.
167
T. Horie, M. Tsukayama, M. Masumura, M. Nakayama, and S. Hayashi, Bull. Chem. Soc. Jpn., 1979,
52, 2950.
168
M. Iinuma and S. Matsuura, Yakugaku Zasshi, 1979,99. 657.
169
M. E. Ali, K. M. Biswas, and S. A. Chowdhury. Pak. J. Sci. Ind. Res., 1972, 15, 33.
173
J. A. Van Allan, J . F. Stenberg, and G. A. Reynolds, J. Heterocycl. Chem., 1979, 16, 1663.
(205) R = H (207) R = H or Me
(206) R = OH
the dihydroxy-deriyative (2O6).I7l A large number of flavone-6-, -7-,and -8-

carboxylic acids and related compounds have been synthesized by mostly stan-
dard procedures and screened for antiallergic A flavone called 5 -
methoxyayanin A, obtained from Apuleia leiocarpa, has been ~ y n t h e s i z e d . ' ~ ~
The mass spectrometric behaviour of flavones has been and the use
of U.V.and n.m.r. spectroscopy to show the position of bulky groups in aceto-
phenones and flavonoids has been illustrated in a study of the behaviour of these
compounds on addition of AlCl, (u.v.) and deuteriated pyridine (n.m.r.). 174
Irradiation of these compounds in aqueous methanol, containing an excess of
Na2S03,gave a good yield of the dimers (207).17'
Flavones undergo oxygenolysis, which is base-catalysed, and the product
depends on reaction conditions; for example, with oxygen and t-butoxide ion in
DMF, 3,4'-dihydroxyflavone gave a high yield of 2-(4-hydroxybenzoyloxy)ben-
zoic acid and CO in 30 minutes. A mechanism involving attack at C-2 and
formation of a peroxide has been suggested. Some flavones gave a mixture of
Reduction of 3-methoxyflavone (208) with a large excess of sodium
in liquid ammonia was regiospecific, giving 32% of the dihydrochalcone (209)
and a yield of 27% of the dimeric dihydrochalcone (210).177Heating substituted
7-(preny1oxy)flavones (2 11)in diethylanilhe (212) gave dihydrofuro[2,3-h]flav-
ones (213), but similar treatment of 7-(prenyloxy)isoflavones resulted only in
rearrangement of the ~ i d e - c h a i n . ' ~ ~
171 S. F. Chang and K. K. Hsu: T'ai-wan K'o Hsueh, 1978,32, 87.

172 G. Doria, C. Romeo, A. Forgione, P. Sberze, N. Tibolla, M. L. Corno, G . Cruzzola, and G . Cadelli,
Eur. J. Med. Chem., 1979,14, 347.
173 J. Muradian and P. C. Ferreira, An. Farm. Quim. Sao Paulo, 1978, 18, 125.
174 R. Alves de Lima and G . Delle Monache, Rend. Accad, Nuz. 40 [Quaranta], 1978,3, 181.
175 I. Yokoe, M. Taguchi, Y. Shirataki, and M. Komatsu, J. Chem. SOC.,Chem. Commun., 1979, 333.
176 A. Nishinaga, T. Tojo, H. Tomita, and T. Matsuuro, J. Chem. SOC.,Perkin Trans. 1, 1979, 2511.
177 J. G. Sweeny, T. Radford, and G . A. Iaccobucci, J. Org. Chem., 1979,44, 1494.
17' A. C. Jain, D. K. Tuli, and R. Khazanchi, Indian J. Chem., Sect. R, 1978,16, 973.
The following flavones are a selection of the natural compounds which have
recently been identified. Gomphrenol (214) is a new flavone, isolated from the
leaves of Gomphrena globosa that was infected by a virus.1795-Methoxysal-
vigenin (215) has been isolated from the leaves of Salvia oficinalis by extraction
with ether. 180 A Nigerian plant, Ageratum conyzoides, believed to have wound-
healing properties, has been shown to contain 5-methoxynobiletin
(5,6,~,8,3',4',S'-heptametho~vflavone),~~' which was also found in Eupatorium
coelestinum together with another new flavone, i.e. 5,6,7,8,5'-pentamethoxy-
3',4'-methylenedio~yflavone.~~~ 7,5'-Dimethoxy-3,5,2'-trihydroxyflavone is
present in an Indian plant, Inula cappa D.C.,163and 6,4'-dimethoxy-3,5,7,3'-
tetrahydroxyflavone (laciniatin) in the leaves of Brickellia laciniata. l g 3 Another
new flavone, 5,7,2',4'-tetramethoxyflavone,which is present in the fruits of
Terminalia arjuna, has been synthesized from 2,4-dimethoxy-6-hydroxy-
acetophenone and 2,4-dimethoxybenzoyl ~ h l o r i d e . The
' ~ ~ highly oxygenated
flavones (216) and (217) are present in the farinaceous exudate of Notholaena
and (218) comes from a South African plant, Heteromma decurrens."'
~ffinis,'~~
(216) R' = R2 = OMe,R3 == H , R 4 = OH

(217) R ' = R2 = R4 = O M e , R 3 = H
(218) R' = OH, R2 = H, R3 = R4 = OMe
M. L. Bouillant, P. Redolfi, A. Cantisani, and J. Chopin, Phytochemistry, 1978, 17, 2138.

"O C. H. Brieskorn and Z. Kapadia, Plantu Med., 1979, 35, 376.
18' E. K. Adesogan and A. L. Okunade, Phytochemistry, 1979,18, 1863.
182 N. Le-Van and T. V. C. Pham, Phytochemistry, 1979, 18, 1859.
B. N. Timmermann, R. Mues, T. J. Mabry, and A. M. Powell, Phytochemistry, 1979, 18, 1855.
A. Nager, V. K. Gujral, and S. R. Gupta, Phytochemistry, 1979, 18, 1245.
lR5 M. Jay, J. Fabre-Bonvin, and E. Wollenweber, Can. J. Chem., 1979, 57, 1901.
F. Bohlmann and U. Fritz, Phytochemistry, 1979. 18. 1080.
(219) R ' = R 3 = H, R2 = OMe, R4 = H&Me20Ac

(220) R ' = R 2 = Ri = R4 = H ; A'
(221) R ' = OMe, R2 = R3 = R4 = H ; A'
The structures originally assigned to three flavones present in Lychnopheru
ufinis have now been revised, and all are derivatives of 3,7-dimethoxy-5,3',4'-
trihydroxyflav~ne.'~~A new dihydrofuro[2,3-h]flavone (219),called polystachin,
has been isolated from Tephrosia poly~tachyu,"~and two furo[2,3-h]flavones
(220) and (221) are present in the roots of Derris mollis.'"
1soflavones.---In contrast to the behaviour of 7-(prenylo~y)flavone,'~* 7-(prenyl-
oxy)isoflavone, on heating in dimethylaniline, is not converted directly into
dihydrofuro[2,3-h]isoflavone but needs further heating.'7REarlier work by the
workers at Debrecen on the ring-cleavage of 4-pyrones by nitrogenous
nucleophiles has been extended to isoflavones, which gave 4,5-diaryl-pyrazoles
on treatment with hydrazines.'" These workers have also determined the rate
of cleavage of the pyrone ring of isoflavone and other pyrones by alkali by the
use of U.V.spectroscopy. The rate-determining step is the initial addition of
nucleophile at C-2 to give the carbanion, which is stabilized by loss of H' (Scheme
6). The rate of this first step depends on the electron distribution in the ground
state, especially that at C-2.19'
Scheme 6
A useful method for selective 0-acetylation of 5,7-dihydroxyisoflavones has

been described. Acetic anhydride and pyridine gives the 7-acetoxy-compound
whereas acetic anhydride and perchloric acid yields the 5 -acetoxy-isomer;
nuclear chlorination of the latter occurred at C-8 when it was treated with ethyl
NN-dichlorocarbamate.192 Interaction of isoflavones (222) with Grignard
reagents and copper@ chloride gave the deoxybenzoin (223), which was used in
the synthesis of stilbene-like
ln7 P. W. LeQuesne, M. D. Menachery, and R. F. Raffauf, J. Nut. Prod., 1979,42, 320.
lnR R. Vleggaar, T. M. Smalberger, and J. L. Van Aswegen, S. A f r . J . Chem., 1978, 31,47.
18' D. A. Lyra, J. F. De Mello, G. Delle Monache, F. Delle Monache, and G . B. Marini-Bettolo, G a z z .
Chim. ltal., 1979,109, 93.
O'' V. Szabo, J. Borda, and V. Vegh, Acta Chim.Acad. Sci. Hung., 1978,98,457.
lyl M. Zsuga, V. Szabo, F. Korodi, and A. Kiss, Actn Chim. Acad. Sci. Hung., 1979,101, 73.
19' R. J. B a s , J. Chem. SOC.,Chem. Commun., 1979, 264.
I Y 3C. K . Sehgal, P. L. Kachroo, and K. L. Dhar, Indian J . C'hem., Sect. B,1979, 17, 182.
0 0
(222) (223)
A Panamanian tree (Gliricidia sepiurn) whose heartwood is resistant to some

boring insects contains a number of flavonoids, including two new compounds,
namely 4’-methoxy-7,3’,5’-trihydroxyisoflavone (gliricidin) and 4’-methoxy-
’ ~ seed shells of Derris robusta
3,7,3’,5’-tetrahydroxyisoflavanone( ~ e p i n o l ) . ~The
contain a new isoflavone called derrugenin (5,5’-dihydroxy-7,2‘,4’-
trimethoxyis~flavone),’~~ which is closely related to robustigenin (5-hydroxy-
7,2’,4’,5’-tetramethoxyisoflavone),obtained from the same s ~ u r c e . ’ ’The ~ latter
compound and its 5-methyl ether have been synthesized and their structures thus
confirmed.
Thioflavans and Thioflavones.-The diketone (224; R = H or Ar) has been
cyclized to the thiopyrylium ion ( 2 2 5 )and a small amount of the thioflavan (226)
by treatment with H2S and CF3C02H.A similar reaction was described for the
corresponding cy~lopentanone.’’~
a z H c RH 2 c II* r - mAr+
WAr R/
R
(224) (225) (226)
Thioflavone has been chlorinated at C-3 by reaction with thionyl chloride. This
chlorinated derivative was converted into the sulphone by H z 0 2 and AcOH.
However, thioflavone, when treated with sulphuryl chloride and then an alcohol,
was simultaneously dichlorinated and alkoxylated to give a thioflavanone. 19’
Dihydroisocoumarins.-Diazoethyl ketones (227), on warming with acid, gave
isochroman-2,4-diones (228) in good yield, and their reduction with NaBH,
yielded the dihydroisocoumarins (229).200 3,3-Disubstituted dihydro-
isocoumarins (2321, related to some natural compounds, have been synthe-
M e O&
Me0 \
M/ C0,Me
CN,Me
- M
Me0 \
e c a
Me
(227) R
(228) R = 0
(229) R = H2
194 G. D. Manners and L. Jurd, Phytochemistry, 1979, 18, 1037.
19’ S. S. Chibber and R. P. S h a m a n , Phytochernistry, 1979, 18, 1583.
196 S. S. Chibber and R. P. Sharma, Phytochemistry, 1979, 18, 1082.
19’ S. S. Chibber and R. P. Sharma, Indian J. Chem., Sect. B, 1979, 17, 76.
19’ T. V. Stolbora, S. K. Klimenko, and V. G. Kharchenko, Zh. Org. Khim., 1980, 16, 178.
199 J . R. Merchant, G. Martyres, and S. Dike, Chem. Ind. (London), 1979, 350.
*O0 J. N. Chatterjea, N. D. Sinha, and C. Rhakta, J. Indian Chem. Soc., 1979, 56, 515.
sized in one step from styrenes (230; Ar = MeOC6H4, MeC6H4, etc.) and
o-chloropalladiobenzoic acid (231). A methyl group on the a-position of the
styrene is essential.”l
Several new dihydroisocoumarins, e.g. (233), have been isolated from a fungus
(Fusarium larvarum) which is a pathogen of some insects.20’ Another fungus
(Aspergillus terreus ARRL 6273), sometimes present in hay, produces several
toxins, including a new compound called terretonin (234).’03 Penicilliurn citreo-
viride produces several compounds which have bactericidal and insecticidal
activity. One of these is semi-vioxanthin (235).’04 Streptornycesrosa also produces
compounds which have antibacterial action; for example, nanomycin E (236),
which is an epoxy-derivative of nanomycin A.’05
- Lll2Lll
I
(CH,’ ‘-
(233) R’ and R2 = H, Me (234)
(236)
Coumarins.-6-Hydroxy-7-methoxybenzofuran-5-carboxaldehyde undergoes a
Wittig reaction with ethoxycarbonylmethylenetriphenylphosphoraneto give the
trans-acrylic acid (237), which is thermally cyclized to methoxsalen (238) in high
yield. A I4C label may be incorporated at C-4 by this method.206During the
synthesis of furopinnarin (240) from bergaptol(239), the first example of a para
Claisen rearrangement of a prenyl ether was ~ b s e r v e d . ”Existing
~ syntheses of
furocoumarins containing a methyl in the a-position of the furan are tedious. A
simultaneous Claisen rearrangement and cyclization to the a-methylfuran
20 1
H. Horino and N. Inoue, Heterocycles, 1978, 11, 281.
202
J. P. Springer, J. W. Dorner, R. J. Cole, and R. H. Cox, J. Org. Chem., 1979, 44, 4852.
203
J. F. Grove and M. Pople, J. Chem. Soc., Perkin Trans. 1, 1979, 2048.
204
A. Zeeck, P. Russ, H. Laatsch, W. Loeffler, H. Wehrle, H. Zachner, and H. Holst, Chem. Ber., 1979,
112,957.
20s
M. Kasai, K. Shirahata, H. Tanaka, and S. Ornura, J. Antibiof., 1979, 32, 442.
206
Y. Y. Liu, E. Thorn, and H. A. Liebrnan, J. Heterocycl. Chem., 1979,16, 799.
207
R. D. H. Murray and K. W. M. Lawrie, Tetrahedron, 1979, 35, 697.
312
@:=c" I
CO,Et
aMe \R 2 /
\ Me
/
(238) R' = Me, R2 = H (241)

(237)
(239) R' = R2 = H
(240) R' = Me, R2 = CMe2CH=CH2
derivative (24 1) occurred when 7-(~-halogeno-allyloxy)coumarins were heated

for 24 hours in diethylaniline.208
A metabolite (242) of methoxsalen [-xanthotoxin (238)], which is used in the
treatment of psoriasis, has been totally synthesized from 7-hydroxycoumarin.
Several derivatives of another metabolite (243) have been prepared from the
aldehyde (244).20'
0 R'
(242) R' = R3 = H , R 2 = O H (245) R = CO2Et (247)
(243) R' = R2 = OH,R3 = H (246) R = H
(244) R' = R2 = H , R 3 = AC
Condensation of 4,6-dimethoxy-2-hydroxyacetophenone with diethyl car-
bonate and an alkoxide ion has now been shown to give the coumarin-3-
carboxylic ester (245), and not 4-hydroxy-5,7-dimethoxycournarin (246), as
originally reported. Heating the ester with aqueous alkali resulted in hydrolysis
and decarboxylation to (246).210 The well-established acid cyclization of salicyl-
aldehyde with ethyl cyanoacetate to give coumarin-3-carboxylic acids has been
studied in alkaline media and found to give the ester (247; X = 0) and the
imino-ester (247; X = NH). When the proportion of the cyano-ester was
increased, high yields of the latter were obtained.211
The lithium derivative of the 2-(methoxymethoxy)naphthalene (248) has been
treated with diethyl ethoxymethylenemalonate to produce moderate yields of
6,7-benzocoumarin-3-carboxylateesters (249) in a one-pot reaction.212The
ortho-lithiation of (methoxymethoxy)benzenes, followed by reaction with DMF
'ORK. D. Kaufman and L. E. Hewitt, J. O r g . Chem., 1980,45, 738.

'09P. N. Confalone and D . L. Confalone, J. Org. Chem., 1980, 45, 1470.
V. K. Ahluwalia and D. Kumar, Indian J. Chem., Sect. B, 1979, 17, 167.
2" A. A . Avetisyan, Z . V. Vanyan, and M. T. Dangyan, Khim. Geterotsikl. Soedin., 1979, 1181
'" G. A. Kraus and J. 0. Pezzanite, J. Org. Chem., 1979, 44, 2480.
Reagents: i, BuLi, DMF; ii, HCI; iii, Ph,P=C(Ph)CO,Et
Scheme 7
and HCl to remove the ether grouping, gave the corresponding o-hydroxybenz-
aldehyde; on treatment with a Wittig reagent, this cyclized to the appropriate
3-phenylcoumarin (Scheme 7).213
4-Phenylated coumarins have been synthesized by the reaction of cinnamic
acid with 4-substituted phenols in the presence of BF3.*14Methyl benzoquinone-
2-carboxylate condenses with various phenols, under acid catalysis, to give
6H-dibenzo[b,d]pyrans (250), which may be oxidized to the 7,lO-quinone and
converted into other
In the synthesis of coumarins by the von Pechmann reaction, a spiro-compound
(251) was simultaneously formed from 4-chloro-2-methylphenol (and from
2,3,5-trimethylphenol). A possible mechanism for this reaction involves the
formation of the lactone (252), which reacts with another molecule of the
The condensation of the dicyano-ester (253j [obtained from
malononitrile and ethyl cyanoacetate] with substituted o-hydroxybenzaldehydes
yields substituted coumarinimines, e.g. (254).”’ A series of 4,6,7-substituted
coumarins have been prepared and assessed for their suitability in fluorescence
labelling of Esters of the type PhCH=CRC02Ar react with AlC1,
to give coumarins, which are probably formed via dihydrocoumarins (255) by
dearylation.*I9
R+@
OH 0 Me
(250) R = Me, C1, or M e 0 (251)
NCCH ,C=CCO,Et
I I
H,N CN C=CCO,Et
(253) I Ph
(255)
N. S. Narasimhan, R. S. Mali, and M. V. Barve, Synthesis, 1979, 906.

214 S. P. Starkov, Izv. Vyssh. Uchehn. Zaved., Khitn. Khirn. Tekhrzol., 1979, 22, 1327.
P. Mueller, T. Venakis, and C. H. Eugster, Helv. Chim. Acta, 1979, 62, 2833.
216 J. L. Belletire, K. Donahue, and M. Kellogg, J. Heterocycl. Chem., 1979, 16, 803.
217 H. Junek, B. Thierrichter, and P. Wibmer, Monatsh. Chem., 1979, 110, 483.
218 J. Krejcoves, J. Drobnik, J. Jokl, and J. Kalal, Collect. Czech. Chem. Commun., 1979, 44, 2211.
21y T. Manimaran and V. T. Ramakrishnan, Indian J. Chern., Sect. B, 1979, 18, 324.
Coumarins that are labelled with isotopes have been synthesized; for example,
(R)-
and (S)-warfarins with tritium at the 4 ' - p o ~ i t i o n ~and
~ ' 3-chloro-7-hydroxy-
4-[1'C]methylc~~marin.221
The "C n.m.r. spectra of a number of coumarins have been correlated with
Hammett constants222and with Swain-Lupton and Schaefer parameters.223
Coumarin and some of its methoxy-derivatives undergo acetoxymethylation,
usually at C-3, in yields of up to 87% when heated with rnanganese(II1) acetate
in a solvent such as acetic acid-acetic anhydride. Varying amounts of the
3-(diacetoxymethy1)-derivativeswere also isolated in some experiments, and in
the reaction with 7,8-dimethoxycoumarin the benzene ring was sufficiently
reactive to allow the formation of 3,6-di(acetoxymethyl)-7,8-dimethoxy-
~ o u m a r i n . ~Ring-contraction,
~~' of 4-(chloromethyl)coumarin in aqueous alkali
proceeded in 92% yield to give benzofuran-3-acetic
Grignard reactions on coumarins are a source of various compounds; for
example, coumarin and methylmagnesium iodide yields 2,2-dimethylchromene
and nine other products, which have been identified by g . l . c . - m . ~ . A~ ~similar
~
reaction on 8-methoxy-6-methylcoumaringave 8-methoxy-2,2,6-trimethyl-
chromene, which was oxidized by DDQ to the 6 - c a r b o ~ a l d e h y d eThe
. ~ ~ reaction
~
of 3,4-diaryl-coumarins with methylmagnesium iodide gives various products,
depending on the substituents present, the polarizability of the carbonyl group,
and the reaction
A single-step benzoylation-oximation has been described on 4-hydroxy-
coumarin by the use of PhCCl=NOH228 and Et'N in boiling When
7-methoxy-8-prenylcoumarin (osthol) or its epoxide was treated with various
Lewis acids, several products were obtained. These resulted from migration or
disappearance of the exocyclic double bond, abnormal Friedel-Crafts phenyl-
ation, hydration, cyclization, or demethylation.2'o A novel ring-opening of
coumarins was effected by treatment with alkyl halides and NaH in THF. The
cis-o-alkoxycinnamic acid was obtained mainly or exclusively.231
(256) R' = H, R2 = CH2CH(OH)CMe=CH2, R' = Me, R4 = H

(257) R' = R2 = CH2CH==CMe2,R' = R4 = H
(258) R' = H, R2 = OMe, R' = CH2CH=CMe2, R4 = OH
220 C. E. Cook, C. R. Tallent, N. H. Ballentine, G . F. Taylor, and J. A. Kepler, J. Labelled Compd.
Radiopharm., 1979, 16,623.
221 J. P. H. Mueller, A. Attar, H. J. Kurth, and D. Bienick, J. Labelled Compd. Radiopharm., 1978,
15(suppl), 261.
222 H. E. Gottlieb, R. Alves de Lima, and F. Delle Monache, J. Chem. Soc., Perkin Trans. 2, 1979,435.
223 A. Rabaron, J. R. Didry, B. S. Kirkiacharian, and M. M. Plat, Org. Magn. Reson., 1979, 12, 284.
224 ( a ) K. Kurosawa and H. Haralda, Bull. Chem. Soc. Jpn., 1979, 52, 2386; (6) V. I. Dulenko, V. M.
Golyak, V. I. Gubar, and N. N. Alekbeev, Khim. Geterotsikl. Soedin., 1979, 992.
225
K. Jankowski, Y. Volpe, and C. S . Del Campo, Rev. Latinoam. Quim., 1979, 10, 87.
226 M. V. Naidu and G . S . K. Rao, Proc. Indian Acad. Sci., Sect. A, 1979, 88, 197.
227 S. Ray, M. Kumari, P. L. Kole, P. K. Grover, and N. Anand, J. Indian' Chem. Soc., 1978,55, 1181.
228 R. H. Wiley and R. Weikfield, J. Org. Chem., 1966, 25, 546.
229 P. L. K. M. Rao and K. S. R. Krishna Mohan Rao, Indian J. Chem., Sect. B, 1979,17, 398.
23n J. Banerji, R. N. Rej, A. Chatterjee, and A. Banerji, Indian J. Chem., Sect. B,1979, 17, 113.
*" C. K. Sehgal, P. L. Kachroo, S. C. Taneja, K. L. Dhar, & C. K. Atal, Synth. Cornmun., 1980,10,37.
Numerous new coumarins have been identified in plants: apigravin (7-

hydroxy-8-methoxy-6-prenylcoumarin) occurs in the seeds of Apium
g r a ~ e o l e n s ; ~6-(2-hydroxy-3-methylbut-3-enyl)-7-methoxycoumarin
~~ (256)
and 3,6-diprenyl-7-hydroxycoumarin (257), present in Amyris balsamifera,
provided taxonomic evidence;233capensin (258) has been discovered in the aerial
parts of the South African plant Phyllosma ~ a p e n s i s . ~ ~ ~
Isocoumarins and Related Compounds.-When 2- or 4-chloro-N-methylbenz-
amide (259) was lithiated and treated with propylene oxide (260), a moderate
yield of the dihydroisocoumarin (26 1) was obtained, which could be dehydrog-
enated with NBS and benzoyl peroxide to the corresponding i ~ o c o u m a r i n . ~ ~ ~
The 16-oxa-steroid (262), previously has been converted into a
number of other 16-oxa-steroids in which ,the carbonyl group is absent.237
(262)
A new acetylenic isocoumarin called 8-hydroxycapillarin [3-(but-2-ynyl)-8-
hydroxyisocoumarin] has been isolated from Artemisia d r a c u n c ~ l ~ ~ . ~ ~ ~
Xanthenes.-When duroquinone (263) was reduced electrochemically, a high
yield of diduroquinone (264) was produced by a catalytic amount of current.
Several possible mechanisms for the dimerization have been When
the p-benzoquinone (265) was heated in pyridine, it dimerized, in good yield, to
the xanthene (266); this rearranged when treated with acids or bases.240Another
(265) (266) Ar = 4-MeOC6H4

232 S. K. Garg, S. R. Gupta, and N . D . Sharma, Phytochemistry, 1979, 18, 1580.
233 B. A. Burke and H. Parkins, Phytochemistry, 1979,18, 1073.
234 W. E. Campbell and G. M. L. Cragg, Phytochemistry, 1 9 7 9 , 1 8 , 6 8 8 .
235 B. H. Bhide and V. P. Gupta, Indian J. Chem., Sect. B, 1979,17, 295.
236 T. Terasawa and T. Okada, Heterocycles, 1978, 11, 181.
237 T. Terasawa and T. Okada, J. Heterocycl. Chem., 1979, 16, 637.
238 H. Greger and F. Bohlmann, Phytochemistry, 1979, 18, 1244.
239 R. D. Ricke, T. Saji, and N. Kujundzic, J. Electroanal. Chem. Interfacial Electrochem., 1979, 102,
397.
240 L. Jurd, J. N. Roitman, and R. Y. Wong, Tetrahedron, 1979, 35, 1041.
316 He terocy c 1ic Chem is try
synthesis uses a dimer of 5-methoxy-2-(4-methoxyphenylmethyl)-1,4-
benzoquinone, which is converted into the xanthylium salt (267) by strong acid.14'
Catalytic reduction of bicyclic 1,5-diketones, e.g. (268),in the presence of Group
VIII metal catalysts gave the reduced xanthene (269).242Piperonal has been
uI"(;O
converted into (*)-puupehenone (270), which is present in a genus of marine
sponge, in six steps.243
i9hQ'i
--+
(269)
OMe
(267)
Xanthenyliumsodium (from sodamide and xanthene) reacts with aziridines to
give a mixture of 9-mono- (27 1) or 9,9-di-substituted xanthenes (272).244Addi-
tion of perchloric acid to unsymmetric allenes such as the 9-xanthylidene deriva-
tive (273) (prepared by a new route from 9,9-dichloroxanthene and an alkene)
gave a red xanthylium salt (274), which was converted into a colourless spiro-
indene (275) on heating.245Full details have now been published of the properties
and of the reactions of 9-diazoxanthene (276) and 9-xanthylidene (278)with
methyl acrylate, substituted styrenes, several ketones, and a l k y l - b e n ~ e n e sThe
.~~~
a
kinetics of the reaction with styrenes were studied and the conversion of (276)
into (278) was achieved by photolysis of the tosylhydrazone (277) at -25 "C.
\ /
R
(273) R = C=CPh2
(271) R2 = H
(276) R = N2
(272) R2 = (CH2)2CNHR'
I/ (277) R = NNHS02C6H4Me-p
0
(274) f 275)
241 L. Jurd and J. N. Roitman, Tetrahedron, 1979, 35, 1567.
242 V. G. Kharchenko, V. N. Kravtsova, A . D. Shebaldova, and A. A . Terekhin, Z h . Urg. Khim., 1979,
15, 1412.
243 G. L. Trarnrnell, Tetrahedron Lett., 1978, 1525.
244 H . Starnni and W. Wiesert, Arch. Pharm. (Weinheim, Ger.), 1979, 312,133.
24s N. F. Abdul-Malik, S. B. Awad, and A. B . Sakla, Bull. Chetn. SOC.Jpn., 1979, 52, 3431.
24h G. W. Jones, K . T. Chang, and H. Shechter, J. A m . C'hem. Soc., 1979, 101, 3906.
0
(279) R1 = OH, R2 = H
(280) R1 = H, R2 = OH
Two new pigments (279)and (280) have been isolated from the flowers and
roots of Australian plants.247
Xanthones.-An efficient and convenient method of preparing xanthone in 99%
yield is to heat o-phenoxybenzoic acid for 20 minutes at about 155 "C in molten
sodium tetrachlsroaluminate, obtained by fusing sodium chloride and aluminium
Xanthones (283) were formed by cyclization of diphenyl ethers such
as (282), which were prepared by addition of p-cresol to the quinone esters (281)
followed by reductive m e t h y l a t i ~ n . ~ ~ ~
OMe
b C 0 2 M e + M
a e 0: o COMe
M e -
M
We 0 M e
0 0
(281) (282) (283)
(284) (285)
2-(2,4-Dioxopentyl)-2-hydroxychromanones, such as (284), have been cyclo-
dehydrated in high yield, under alkaline conditions, to the xanthone (285); this
route resembles biosynthetic In a synthesis of benzoxanthones, a
photo-induced Fries rearrangement of a 2-benzoyloxy-4-methoxy-6-methylben-
zoyl ester was employed, but in several experiments a mixture of ketones was
obtained. However, when the diester (286) was similarly treated, it gave the
ketone (287), which cyclized to the xanthone (288).251
Identification of xanthones on t.1.c. by spray techniques is difficult, as there is
no specific reagent, but i ~ d o p l a t i n a t egives
~ ~ ~colours which differentiate these
compounds from coumarin, flavone, etc. Prenylated xanthones d o not
247 R. G. Cooke and T. J . Dagley, Aust. J. Chem., 1979, 32, 1841.
248 L. G. Wade, K. J. Acker, R. A. Earl, and R. A. Osteryoung, J. Org. Chem., 1979, 44, 3724.
249 P. Mueller, T. Venakis, and C. H. Eugster, Helu. Chim. Acta, 1979, 62, 2350.
R. M. Sandifer and T. M. Harris, J. Chem. SOC.,Chem. Commun., 1979,442.
T. Kato, J. Nakano, and N. Katagiri, Heterocycles, 1979, 12, 1013.
252 R. Munier, Bull. Soc. Chim. Fr., 1952, 852.
253 A. A. L. Gunatilaka and C. Wickrernage, Chem. Ind. (London), 1979,659.
OAc OBn Me0
R
(286) R = H OBn
(288)
(287) R = COAr
Ar = 2-OCH2Ph-4-OMe-6-MeC6H2
Bn = CH2Ph
The mass spectrum of 5-hexyl-7-(S-methylsulphonimidoyl)xanthone-2-
carboxylic acid exhibits a peak which has m / z that is 14 units higher than the
molecular peak. It has been shown that this arises from an intermolecular transfer
of a methyl group (which occurs also when the compound is heated) but a
carboxylic acid group is
An unusual method of preparing pyran-4-thiones has been demonstrated on
benzoxanthones, which were treated with tosyl isocyanate to give the sulph-
onamide (289a). This was converted into the 9-thione (289b) by butylamine
and H2S.255
(289) a; R = NTs
b;R = S
(290)
A bispiran (290) was synthesized by condensation of 2-chloroxanthene-9-
thione with 9 - d i a z o f l ~ o r e n e . ’ ~ ~
Pinselic acid (293) and related compounds, isolated from Penicillium amarum,
have been synthesized from 3,6-dimethoxyphthalic anhydride and the lithium
derivative (291) uia the ketone (292).2s7A number of the chlorinated xanthones
found in lichens have been synthesized and their structures verified, using 13C
~ ’ roots of Hypericum androsaemum contain several xanthones, two
r ~ . m . r . ~The
of which [(294) and (295)] have an oxygenation pattern not previously known
2s4 A. C. Barnes, P. W. Hairsine, D. P. Kay, P. J. Rarnrn, and J . B. Taylor, J. Heterocycl. Chem., 1979,16,
1089.
”’ J. A. Van Allan, G. F. Reynolds, and J. F. Stenberg, J. Heterocycl. Chern., 1979, 16, 1661.
256 F. M. E. Abdel-Megeid, A. A. Elbarbary, and F. A. Gad, Pol. J. Chem., 1979, 53, 1877.
2s7 K. K. Law, T. L. Chan, S. W. Tam, and N. T. Shatin, J. Org. Chem., 1979,44,4452.
E. G. Sundholm, Acta Chem. Scand., Ser. B, 1979, 33,475.
R 2 a
OMe H O W
R' \ R\ 0
0 O R R
(294) R' = OH,R2 = H (296) R = CH2CH=CMe2
(295) R' = OMe,R2 = OH
in Nature.2s9A new reduced xanthone called zeyloxanthonone (296) has been
identified in a Sri Lankan plant, Culophyllum zeylunicum.2h0An addition to the
list of xanthones present in aerial parts of Cunscoru decussutu is 3,6-dihydroxy-
1,5,7-trimethoxyxanthone.26'
Thioxanthenes.-The method of synthesizing xanthones that was mentioned in
the previous has also been applied to the corresponding thioxanthones.
A compound which was described262as 9,lO-diphenyl-10-thia-anthracene has
been shown to contain mono-, di, and tri-phenylthi~xanthene.~~~
Deuterium labelling and n.m.r. spectroscopy have been used to study the
conformation of thioxanthenium methylides which exist in the e' conforma-
t i ~ n The
. ~ stereochemistry
~ ~ (including conformation) of 9-(ary1)thioxanthene
10-oxides and 10,lO-dioxides has also been investigated.265
The cis- and the trans-9-substituted thioxanthene-N-(toluene-p-
sulphony1)sulphilimines (297 ; R = alkyl or aryl) rearrange to 9-substituted 9-(N-
toluene-p-su1phonamido)thioxanthenes(298). The effect on this reaction of the
stereochemistry and the character of the 9-substituent has been studied, using
'H and I3C n.m.r. and lanthanide shift reagents.266 A parallel reaction on a
thioxan thenium bis(me t hoxycarbon yl) meth ylide (299), giving (300), has also
X
(297) X = NTs (298) X = NHTs

(299) X = C(CO,Me), (300) X = CH(CO,Me),
been described, the substrate being synthesized in 66% yield from thioxanthene
and dimethyl diazomalonate. The product varies with Acid-catalysed
isomerization of the reduced thioxanthene (301) has given a product which X-ray
analysis showed to be (302); its bond lengths and angles have been determined.268
259 H. Nielsen and P. Arends, J. Nut. Prod., 1979, 42, 301.

260 S. Karunayake, S. Sotheeswaran, and M. U. S. Sultanbawa, Tetrahedron Lett., 1979, 1449.
S. Ghosal and K. Biswas, Phytochemistry, 1979,18, 1029.
262 C. C. Price, M. Hori, T. Parasaran, and M. Polk, J. A m . Chem. SOC.,1963, 85, 2278.
263 M. Hori, T. Kataoka, H. Shimizu, Y. Itagaki, and T. Higuchi, Tetrahedron Lett., 1979, 1603.
264 A. L. Ternay, Jr., D. Craig, and H. R. O'Neal, J. Ore. Chem., 1980, 45, 1520.
265 M. Hori, T. Kataoka, H. Shimizu, and S. Ohno, Heterocycles, 1979, 12, 1417.
266 Y. Tamura, C. Mukai, Y. Nishikawa, and M. Ikeda, J. Org. Chem., 1979,44, 3296.
Y. Tamura, C. Mukai, and M. Ikeda, Heterocycles, 1979, 12, 1179.
268 A. A. Shcherbakov, G. G . Aleksandrov, Yu. T. Struchkov, and V. G. Kharchenko, Khim.
5 Heterocycles containing One Oxygen and One Sulphur Atom

Cyclization of benzyl2-carboxyphenyl sulphoxide with DCC led to 2-phenyl-3,l-
benzoxathiin-4-one (303)with 55 “/o retention of sulphoxide oxygen (determined
by using labelled sulphoxide) and a 61 : 38 ratio of enantiomorphs. Acetic
anhydride, if used as the condensing agent, gave a different enantiomorphic
The synthesis and conformations of a- and P-2-methoxy-trans-
hexahydrobenzoxathian 4,4-dioxides have been described. N.m.r. and 13Cn.m.r.
spectroscopy showed that the conformation was ~olvent-dependent.~~’ A number
of sultones (304) have been synthesized by treatment of alkadienes with SO, in
dioxan.”l 4,6-Dimethyl-1,2-oxathiin 2,2-dioxide (306) is the main product of
heating the sulphonic acid (305) with acetic anhydride.272Reductive cyclization
of the sulphonyl chloride (307) yielded a benzoxathianone (308) which suffered
cleavage of the hetero-ring on reaction with a m i n e ~ . ’ ~ ~
Meoo2(304) SO3H Me
0
C’ \
OCHzCO2Me
S0,CI
- a;lo
Cl \
/-7
0L./s’BH
(307) (308) (309)
The conformations of isomers of 2,6-dichloro-1,4-oxathian have been deter-

mined from C-H spin-spin coupling constants.274 When 6-methyl-1,4-
oxathian-2-one was ethylated, equal amounts of cis- and truns-4-ethyl-6-methyl-
2-0~0-1,4-oxathianiumsalts were formed. Several related compounds were
synthesized, and their stereochemistry was A new hydroborating
agent, borane-oxathian (309), has several advantages over others; for example,
it is stable, moderately soluble in water, and has less odour than others. Its
’” S. Wolfe, P. M. Kazmaier, and H. Auksi, Can. J. Chem., 1979, 57, 2404.
”” D. Lee, J. C. Keifer, R. P. Rooney, T. B. Garner, and S. A. Evans, J. Org. Chem., 1979,44, 2580.
A. V. Semenovskii, E. V. Polunin, I. M. Zaks, and A. M. Moiseenkov, Izu. A k a d . Nauk SSSR, Ser.
Khim., 1979, 1327.
272 S. M. Heilmann, J. K. Rasrnussen, R. A. Newrnark, and H. K. Smith, J. Org. Chem., 1979,44,3987.
’” A. Tippe, E. Siporska, and Z. Eckstein, Pol. J. Chem., 1979, 53, 1905.
274 T. Spoormaker and M. J. A. DeBie, Red. Trau. Chim. Pays-Bas, 1980, 99, 15.
’” E. Kelstrup, J. Chem. SOC.,Perkin Trans. I, 1979, 1029.
hydroborating action in several solvents and on several alkenes has been studied;
for example, with l-methylcyclopentene it gives 94% yield of a product which is
>99% tr~ns-l-hydroxy-2-methylcyclopentane.~~~
6 Heterocycles containing Two Oxygen Atoms

1,3-Dioxans.--A series of 1,3-dioxans (310) have been synthesized, in one step,
from ketones, paraformaldehyde, and a cation-exchanger in its acid form. Good
yields were obtained, provided that the medium was Condensation
of the (lS,2S)-arnino-diol (311) with ketones gave the dioxan, e.g. (312), whose
conformation and configuration have been determined. The results throw light
on the stereochemistry of asymmetrical Strecker 2-Ethoxyacrolein
is a versatile synthon for the synthesis of both 1,3- [e.g. (313)] and 1,4-dioxans
[e.g. (314)] in moderate yields (Scheme 8).279When 5-phenylfuran-2,3-dione
(315) was treated with a carbonyl compound PhCOR (R = H or Me), ring
expansion occurred to give good yields of the dioxen-4-ones (316).28"2-Methyl-
and 2-phenyl-1,3-dioxan-2-thiols(as their sodium salts) have been prepared
from MeCSO(CH2)30H [or PhCSO(CH2),0H] and sodium hydride in
acetonitrile. S-Methylation of the thiols gave the corresponding
orthothioesters.281
Me
Reagents: i, HO(CH,),OH; ii, excess of HO(CH,),OH
Scheme 8
Treatment of 2,4,4-trimethyl-1,3-dioxanunder acid conditions gave 5,6-

dihydro-2,4-dimethylpyran, but related dioxans also gave some 2,3-dihydro-
pyrans.282 Dihalogenocarbenes, generated by phase-transfer catalysis, effect
a regiospecific insertion reaction in 1,3-dioxans (317; R' = H, alkyl, or aryl),
giving (318).283When the methylene-1,3-dioxan (319) is treated with s-butyl-
'"
277
H. C. Brown and A. K. Mandal, Synthesis, 1980, 153.
J. P. Gorrichon, A. Gaset, and M. Delmas, Synthesis, 1977, 219.
278 K. Weinges, K. P. Klotz, and H. Droste, Chem. Ber., 1980, 113, 710.
279 N. A. Keiko, T. N. Musorina, I. D. Kalikhman, and M. G . Voronkov, Zzv. Akad. Nauk SSSR, Ser.
Khim., 1979, 2773.
Yu. S. Andreichikov, L. F. Gein, and V. L. Gein, Khim.Geterotsikl. Soedin., 1979, 1280.
2n1 F. Khouri and M. K. Kaloustian, J. Am. Chem. SOC., 1979, 101, 2249.
282 N. A. Romanov, E. A. Kantor, R. S. MuSavirov, and D. L. Rakhmankulov, Zh. Org. Khim., 1979,
15, 1059.
281
K. Steinbeck, Chem. Ber., 1979, 112, 2402.
(317) R2 = H (319) R = H
(318) R2 = CHX2 (320) R = Me
lithium and an electrophile such as benzaldehyde or methyl iodide, a mixture of

the a-product (320) and the y-product (321) is formed, the components being in
a ratio which is dependent on the presence of salts such as ZnC12.284
The conformations of 1,3-dioxans have been well investigated; for example,
for methyl derivative^,^'^ by the use of ” 0 isotope n.m.r.,286microwave spectros-
copy,287and the relationship with retention time in
1,3-Benzodioxins.-A synthesis of 5- and 8-hydroxy-l,3-benzodioxin-4-ones
from 2,6- and 2,3-dihydroxybenzoic acid, dibromomethane, and benzaldehyde
diacetate has been described.28y NN’-Carbonyldi-imidazolereacts with 2-
hydroxybenzamide to give the 1,3-benzodioxin in 72% yield (Scheme 9). Amides
a;+w
which lack intramolecular hydrogen-bonding react differently.290
c‘=O
NHR NR
R =H or Ph
Scheme 9
2-Alkylbenzo- and 2-alkyl-2-aryl-1,3-benzodioxin-4-oneshave been

degraded to salicylic acid and a mixture of hydrocarbons by treatment with a
Grignard reagent.”’ Reduction with sodium borohydride similarly degraded
2-substituted 1,3-benzodioxin-4-ones but gave salicyl alcohol in high yield.2y2
The 1,3-dioxanoanthracycline antibiotic and anti-tumour agent nogalomy-
cin293has been converted into derivatives in which the sugar attached at C-7 has
been replaced by hydrogen and by alkoxy-groups. This gave stereochemical
2H4 A, P. Kozikowski and K. Isobe, Tetrahedron Lett., 1979, 833.
2xs U. Burkert, Tetrahedron, 1979, 35,691.
2R6 E. L. Eliel, K. M. Pietrusiewicz, and L. M. Jewell, Tetrahedron Lett., 1979, 3649.
*” J. L. Alonso and E. B. Wilson, J. A m . Chem. SOC.,1980.102, 1248.
2nu M. Bartok, J . Chromatogr., 1979, 172, 371.
2xy L. Bonsignone, A. M. Fadda, and G. Loy, Rend. Semin. Fac. Sci. Uniu. Cagliari, 1978, 48, 275.
290 H. Ogata, H. Matsumoto, and S. Kida, Heterocycles, 1979, 12, 1285.
291 S. Mellis and F. Sotgiu, Rend. Semin.Fac. Sci. Uniu. Cagliari, 1978, 48, 261.
292 H. Asakawa, Y. Fukushima, E. Imamiya, and Y. Kawamatsu, Chem. Pharm. Bull., 1979, 27, 522.
293 For a review, see J. R. Brown, Progr. Med. Chevn., 1978, 15, 125.
information, which was supplemented by c.d. studies, relating to the
stereochemistry of C-7, C-9, and C-10.294
1,4-Dioxans and 1,4-Benzodioxins.-l ,4-Dioxans containing either fluorine or
CF, at C-2 and C-3 have been synthesized from perfluorinated 1,2-diketones,
ethylene dimesylate, and KF,295and cis- and trans-2,3-difluoro-l,4-dioxan have
been prepared by allowing trans-2,3-dichloro-l,4-dioxan to react with KF in the
presence of 18-crown-6 ether in acetonitrile. The isomers were separated by g.1.c.
and their conformations were studied, using n.m.r. techniques. The trans-isomer
was largely the diaxial conformer.296A short paper describes the reaction of
triethyl phosphite with 3-acetoxy-2-chloro-l,4-dioxan, which yields a mixture of
A method of determining ‘dioxin’ (tetrachlorodibenzo-p-dioxin), the
highly toxic impurity which is sometimes present in the defoliant 2,4,5-
trichlorophenoxyacetic acid, using mass fragmentation, has been described.298
Irradiation (in the U.V. region) of 1,2,3,6,7,8-hexachloro-1,4-dibenzodioxin
results in loss of one halogen atom, the main product being the 1,2,3,6,8-isomer;
this also underwent further p h o t o d e ~ h l o r i n a t i o n . ~ ~ ~
7 Heterocycles containing Two Sulphur Atoms

1,3-Dithians and 1,4-Dithians.-Equimolar amounts of propane- 1,3-dithiol and
phosgene condensed to give a high yield of 1,3-dithian-2-one by a procedure
which is a considerable improvement on earlier method^.^" A 1,3-dithian is also
obtained when an aldehyde is condensed with a 1,3-dimercaptoacetone (Scheme
The mechanism of the formation of 2,3-dihydro-1,4-dithians (323) from
a-halogeno-acetals (Scheme 11) appears to involve the carbonium ion (322).30’
R’
0
II TsOH sAs
R’CHO + HSCHCCH,SH +
I
R2
0
Scheme 10
BrCH2CH(OEt),
+
HS(CH,), SH
(322) J (323)
Scheme 11
294
P. F. Wiley, D. W. Elrod, D. J. Houser, J. L. Johnson, L. M. Pschigoda, W. C. Kreuger, and A.
Moscowitz, J. O r g . Chem., 1979,44, 4030.
29s W. Schwertfeger and G. Siegemund, Angew. Chem., Int. Ed. Engl., 1980,19, 126.
296 B. Fuchs and A. Ellencweig, J. Org. Chem., 1979, 44, 2274.
29’ V. S. Tsivunin, V. G. Zaripova, T. V. Zykova, and R. A. Salakhutdinov, Zh. Obshch. Khim., 1979,
48, 1906.
298 P. Tancioni and A. Bonetta, Boll. Chim. Unione Ital. Lab. Prov. Parte Sci., 1979, 5 , 449.
299 H. R. Buser, Chemosphere, 1979, 8, 251.
300 S. Satsurnabayashi, S. Motoki, and H. Takahashi, Synthesis, 1979, 184.
301 G . Ginsti, M. Ambrosio, R. Faurt, G. Schembri, E. J. Vincent, and C. Fengeas, C . R . Hebd. Seances
Acad. Sci.,Ser. C, 1979, 288, 441.
S
(324) (325)
Irradiation of the thiadiazine (324) in CS, gave the 1,3-dithian-2-thione (325) as
a minor product, but thermal decomposition produced (325) in 50%
Several compounds have been prepared by nucleophilic substitution of
chlorine in 2-chloro-1,3-dithian with Grignard reagent (RMgBr), malonic esters,
and A mechanism for the de-ethoxycarbonylation of the 2-(1,3-
dithiany1)malonates by sodium chloride or sodium ethoxide has been
2-Chlorotetrahydrofuran reacts with nucleophiles such as 2-lithio-2-phenyl-l,3-
dithian (326) by three simultaneous mechanisms (i.e. substitution, proton
abstraction, and electron transfer) to give the products (327)-(330) (Scheme
12).305When a dithian (331; R = H or C02Me) was treated with a sulphonyl
chloride in pyridine, ring-expansion to the 5H-1,4-dithiepin (332) occurred
instead of the expected formation of a sulphonate."'
(326) (327) R = 2-furd (329) (330) R = S(CH&SCOPh

(328) R = H
Scheme 12
OH
(331) R 0 0 0
(332) (333a) (333b)
8 Heterocycles containing an Oxygen Atom in each of Two Rings

Synthesis.-Application of the Kostanecki-Robinson reaction to 3-acyl-4-
hydroxy-2H-pyran-2-one gave a mixture of pyrano[4,3-b]pyran-4,5-diones
(333), according to the nature of the acyl (Alkyny1oxy)isoflavones
(334), synthesized from 2-chloro-2-methylbut-3-yne and 7-hydroxyisoflavone,
have been cyclized, at 215 "C, to the pyranoisoflavones (335) and (336).308The
302 J . Nakayama, T. Fukushima, E. Seki, and M. Hoshino, J. A m . Chem. SOC.,1979,101,7684.
303 C. G. Kruse, A. Wijsman, and A. van der Gen, J. Org. Chem., 1979,44, 1847.
304 C. G. Kruse, A. C . V. Janse, V. Dert, and A. van der Gen, J. Org. Chem., 1979, 44, 2916.
305 C. G. Kruse, E. K. Poels, and A. van der Gen, J. Org. Chem., 1979,44,2911.
306 P. M. Weintraub, J. Heterocycl. Chem., 1979, 16, 1081.
307 0. Caputo, L. Cattel, F. Viola, and G. Biglino, G a z z . Chim. I d . , 1979, 109, 339.
308 A. C. Jain, R. C. Gupta, and D. K. Tuli, Proc. Nutl. Acad. Sci. India, Sect. A, 1979, 45, 6.
Six-Membered Rings: Other systenzs 325
(334)
basic diester (337) has been synthesized and screened for its ability to intercalate
with DNA.'09 Several pyranobenzopyranones (338), differently substituted on
the pyranone ring, have been synthesized from chromanones via dioxaborins and
aldehyde^.^^" 3-Hydroxycoumarin reacts with unsaturated ketones, e.g.
PhCOCH=CHPh, to give 3,4-dihydropyrano[2,3-c Ibenzopyrans (339).3 1 1 (*)-
Lupinifolin (341) and related flavanones have been synthesized by diprenylation
of 5,7,4'-trihydroxyflavanone (naringenin) in the presence of BF,.Et20 and
cyclodehydration of the product (340) with DDQ.312Pyranobenzopyrandiones
(343) were obtained by oxidation of the chalcones (342) with Se02.313 Although
4-methyl groups in coumarins do not have the reactivity of 2-methyl groups of
chromones, that of ethyl 4-methylcoumarin-3-carboxylate(344) has been con-
[llbenzopyran (345).314
O y C y J y o
R \ \
/R q
do
densed with aldehydes or ketones to form a third ring of a pyrano[3,4-c]-
\
0
Ph
"
0 OH
Ph
(337) R = C02(CH2)2NEt2 (338) (339)
(340) Pn = CH2CH=CMe2 (341)
'09 A. Guiotto, P. Rodighiero, S. M. Magno, 0. Gia, G. Pastorini, P. Manzini, M. Zucca, and I. Viano,
Farmaco, Ed. Sci.,1979, 34, 774.
3 1 0 A. Philipp and I. Jirkovsky, Can. J. Chem., 1979, 57, 3292.
311 V. K. Ahluwalia, K. Bhat, and C. Prakash, Heterocycles, 1979, 12, 1203.
312 A. C. Jain, R. C. Gupta, and P. D. Sarpal, Tetrahedron, 1978,34, 3563.
3 1 3 S. G . Patel and S. Sethna, J. Indian Chem. SOC.,

1979,56,740.
314 K. Ivanov, I . Angelova, and S. Spirova, Synthesis, 1979, 732.
(344) k"
Ph Me
(345)
Properties and Reactions.-Chemical and n.m.r. data have enabled the configur-
ations of the antibiotics griseorhodin A and C to be determined.315 Photo-
oxygenation of the flavene (346; R' = H) proceeds in the presence of oxygen,
but only in alcohols R20H, and gives moderate yields of the diether (347). The
% T2
presence of a methoxycarbonyl group in (346; R1 = C02Me)inhibits photolysis,
but the addition of Rose Bengal as a sensitizer promoted its conversion into the
coumarin (348), which was cyclized by alkali to biscoumarin (349).3'6
/
/
[R' = HI'
\ \
(346) (347)
Naturally Occurring Compounds.-A revised structure (350; R = CMe,OH) for

obtusifol gives it an angular rather than a linear ring arrangement,317and a related
compound, obtusin (350; R = CMe=CH,), has been isolated from Haploghyllus
o b t u ~ i f o l i u mA
. ~ new
~ ~ isoflavone, psoralenol (351),has been identified in the
seeds of Psorulea ~ o r y l i f o l i a .A~ ~prenylated
~ pyrano[3,2-g]isoflavone (352),
called cajaisoflavone, has been isolated from the root bark of the Indian plant
Cujanus c c ~ j a n , ~as~ "also has a closely related isoflavanone (353).321Several
31s K. Eckardt, D. Tresselt, and B. Schoenecker, Tetrahedron, 1979, 35, 1621.
316 K. Shibata, N. Ichikawa, and T. Kubota, Chem. Lett., 1979, 1301.
3'7 A. Z. Abyshev and N. F. Gashimov, Khim. Prir. Soedin., 1979,401.
31R A. Z. Abyshev and N. F. Gashimov, Khim. Prir. Soedin., 1979, 403.
'Iy J. L. Suri, G. K. Gupta, K. L. Dhar, and C. K. Atal, Phytochemistry, 1978, 17,2046.
320 S. Bhanumati, S. C. Chhabra, and S. R. Gupta, Phytochemistry, 1979, 18,1254.
321 S. Rhanurnati, S. C. Chhabra, S. R. Gupta, and V. Krishnamoorthy, Phytochemistry, 1979, 18,693.
Six-Membered Rings: Other systerns 327
OQMe OH 0
(353)
(354) Pn = CH2CH=CMe2
OMe
M e O d L r
0
(355)
prenylated pyrano[3,2-g]flavanones that are present in Mundulea sericea have

been obtained by a biomimetic A new tricyclic chromone (354) is
present in ethanolic extracts from the rhizome of Erunthin h i e m ~ l i s . ~ ~ ~
Peltogynin (355) has been isolated from Acacia fusciculiferu and its structure
has been determined spectroscopically and by preparation from a known com-
Isolisetin dimethyl ether (356), which is related to a flavone present in
the root of Jamaican dogwood, Piscidiu erythrinu, has been
9 Heterocycles containing Oxygen and/or Sulphur Atoms in each of

Two or Three Rings
Successive treatment of bis-3,3-dimethylallenyl sulphone (357) with butyl-
lithium in THF at 0 "C gave a 60% yield of the dithia-adamantane (358), whose
structure was confirmed by X-ray ~ r y s t a l l o g r a p h yPhotolysis
.~~~ of thietans in the
presence of a new triplet sensitizer, 1,3-dimethyl-2-thioxoimidazolidine-4,5-
dione, has produced interesting results; for example, the spiro-xanthone (359)
gave the acetate (360), but in U.V.light, and without the sensitizer, the thiopyran
(361j was obtained in addition to (360).327Among several flavonoids identified
in a Chinese plant, Euphorbia lunulutu Bge., which is used in the treatment of
322
J. J. Van Zyl, G . J. H. Rall, and D. G. Roux, J. Chem. Res. ( S ) , 1979, 97.
323
P.Junior, Phytochemistry, 1979, 18, 2053.
324
F. R. Van Heerden, E. V. Brandt, and D. G. Roux, Tetrahedron Lett., 1979,4507.
325
M. Tsukayama, T. Horie, M. Masumura, M. Nakayama, and S . Hayashi, Heterocycles, 1979, 12,
1539.
326
S. Braverman, D. Reisman, M. Sprecher, D. Rabinovich, and F. Frolow, Tetrahedron Lett., 1979,
901.
327
H. Gotthardt and S . Nieberl, Liebigs Ann. Chem., 1979, 866.
02s
v m
(Me2C=C=CH)2S02
(357)
REoz R
Me02C
(359)
\
CHC0,Me
(360)
(358) R = CMe2
OH
0
(362)
q Me0,C
(361)
chronic bronchitis, a new compound called maoyancaosu (362) was dis-
covered.”’ Compounds containing a pyrano[3,2-b]thiapyran system (364) have
been synthesized by aldol condensation of benzothiopyranone (363) with form-
aldehyde.”’
(-)-Rotenone (365) has been converted (in four stages) into (-)-deguelin (366)
in about 29% yield,330and also into [7’-14C]-and [7’-’3C]-rotenone and [4-I4C]-
and [4-’3C]-rot-2’-enoic Investigation of the components of the leaves
and stems of Amorpha fruticosa showed that one of them was ll-hydroxyteph-
rosin (367), a new r o t e n ~ i d . ~ ~ ~
0
0
HCHO
__+
’” T. M. Shang, L. Wang, H. T. Liang, X. Y. Lin, J . M. Xiao, and S. L. Niu, Hua Hsueh Hsueh Pao, 1979,
37, 119.
729 0. Johansen, T. Ottersen, and K. Undheim, Acta Chem. Scand., Ser. B, 1979, 33, 669.
330 P. B . Anzeveno, J. Org. Chem., 1979,44, 2578.
331
L. Crombie, I. Holden, G . W. Kilbee, and D. A . Whiting, J. Chem. Soc., Chem. Commun., 1979,
1142.
332 L. A. Mitscher, A. Al-Shamma, T. Haas, P. B . Hudson, and Y. H. Park, Heterocycles, 1979,12,1033.
Six-Membered Rings: Other systems 3 29
10 Oxygen-containing Spirans
To the few oxygen- and sulphur-containing spirans327,329mentioned in the
previous section should be added those synthesized by a Russian team who
observed an interesting alkylation or arylation of the spiro[chroman-2,9'-
xanthene] (368) at the 4-position by reaction with a Grignard reagent RMgBr
(R = alkyl or a ~ y l )Bromination
.~~~ of the spiran (369) with NBS gave several
different derivatives of bromochroman, according to the reaction
(368) R = H (370) R = CHMe

(369) R = alkyl or aryl (371) R = 0
11 Heterocycles containing Phosphorus (with or without Oxygen)

The synthesis and some reactions of the aldehyde (371) from the alkene (370)
have been described, e.g. oxidation to the carboxylic acid, reduction to the
4-methyl compound, and Grignard and Wittig reactions.335When the dioxaphos-
phorinan (372), in which all methyl groups are equatorial, was oxidized with
peroxide, a mixture of the stereoisomers (373) was
Ph
(373a) (373b)
Me
I
Ph Cr(C0h PhCHO S
\ / \4
o/p'o dP'0 phYoYph
The 1,3,2-dioxaphosphorin (375) is obtained from the reaction of the diene-

diol form of pentane-2,4 -dione with complexes of phenylphosphonous dichloride
with chromium carbonyl (374).337
333 N. D. Dmitrieva, R. M. Liberzon, 0. P. Brovchenko, and Yu. E . Gerasimenko, Zh. Org. Khim.,
1979,15, 850.
334 N . D . Dmitrieva, R. M. Liberzon, Yu. S . Ryabokobylko, and Y u . E. Gerasimenko, Zh. Org. Khim.,
1979,15,1268.
335 K . Dimroth, H. H. Pohl, and K . H. Wichmann, Chem. Ber., 1979, 112, 1272.
336 B. A. Arbuzov, 0. A . Erastov, S. S . Khetagurova, T. A. Zyablikova, R. A. Kydyrov, and V. N.
Smirnov, Zzv. Akad. Nauk SSSR, Ser. Khim., 1979, 2239.
337 J . von Seyerl, D. Neugebauer, G . Huttner, C. Krueger, and Y. H. Tsay, Chem. Ber., 1979,112,3637.
The stereochemistry of the thiono-thiolo rearrangement of derivatives of
2-thiono-1,3,2-dioxaphosphorinan(376)in trifluoroacetic acid proceeds with
inversion of configuration. The reaction was also investigated in other media.338
From an n.m.r. study of 2,4,5,6-tetraphenyl-1,3,5-dioxaphosphorinan (377),its
P-oxide, and its P-sulphide, all the phenyl groups appear to be in the equatorial
The mechanism of the reaction of phosphorus anilides (378)with
carbonyl compounds to give (wanilinoalky1)phosphonates (379)has been studied
in the presence and absence of an arnine h y d r ~ c h l o r i d e . ~ ~ '
Vinyl acetate reacted with PC15 at about -30°C;treatment of the resultant
compound with ethylene oxide gave the 2,4-dioxaphosphacyclohexane (2,4-
dioxaphosphorinan) (380)in 18.9% yield.341
O+ ,CHPhNHPh
NHPh
OYP'O
W M e
o/p\o
U M e
cl~oT:, P/O
(378) (379) 0
' 'OCH,CH,CI
(380)
12 Heterocycles containing Other Atoms
Cyclization of the dichlorosilane (381)has given a 30% yield of 1,l-dichloro-2-
methylsilacyclohexane (382).342 Silacyclohexadienes such as (383)reacts with
dihalogenocarbenes to give adducts at either of the double-bonds, depending on
the character of R.3431-Arsanaphthalene (384) has been synthesized from
arsabenzene and benzenediazonium 2-carboxylate, and was characterized as its
adduct with hexafluorobut-2 -yne. 344
HC
C1,HSi,
CH2
,(CHZ),
---*
g;
f j ) , M2 e 0 Me2
'c \
R
H2 (382) (384)
(381) (383)
318 K. Bruzik and W. J. Stec, J. Org. Chem., 1979, 44, 4488.

33q B. A. Arbuzov, 0. A. Erastov, S. S. Khetagurova, and T. A. Zyablikova, Izv. Akud. Nauk SSSR, Ser.
Khim., 1979, 2136.
340 M. M. Yusupov, A. M. Abramova, and I. Ya. Gorban, Dokl. A k a d . Nauk Uzb. SSR, 1978, 38.
341 A. A. Krolevets, A. F. Kolomiets, and A. V. Fokin, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 1162.
342 J. Ackerrnann and U. Wannagat, Z . Anorg. Allg. Chem., 1979,459, 37.
343 G. Maerkel, P. Hofmeister, and R. Schiessle, Tetrahedron Lett., 1979, 3503.
344 A. J. Ashe, D. J. Bellville, and H. S. Friedman, J. Chem. Soc., Chem. Commun., 1979, 880.
Seven-Membered Ring Systems
BY J. T. SHARP
1 Introduction
Space limitations dictate that this is a selective (<SO%) rather than a complete
review; in particular, papers and patents where the main objectives were phar-
macological rather than chemical have been omitted.
2 Reviews
Several useful general reviews on seven-membered heterocycles have appeared
in advanced texts,”* and there are also reviews on dihydrodiazepines and their
salts,3 dibenzoxa~epines,~ thiepins,’ fluorinated tricyclic neuroleptics,6 and
the electrochemistry of substances of pharmacological importance (including
dibenzodiazepines).’
3 Azepines and Diazepines

Monocyclic Azepines.-Formation. Two new valence isomers of azepine have
been prepared by photochemical routes. Photolysis of the triazoline (1)gave (2),
which thermally isomerized to N-phenylazepine when R was phenyl, but which
gives a fused oxazoline if R is C0,Et.’
The 3-azaquadricyclane (4)was prepared by photoisomerizing (3); it was

thermally quite unstable ( t l I 2at 70 “Cwas ca. 2 min), and on heating in benzene
it was converted into N-tosylazepine rather than reverting to (3).9
‘Rodd’s Chemistry of Carbon Compounds, Vol. 4: Heterocyclic Compounds, Pt. K,’ (2nd edn.), ed.
S. Coffey, Elsevier, Amsterdam, 1979.
* Comprehensive Organic Chemistry: The Synthesis and Reactions of Organic Compounds, Vol. 4:
Heterocyclic Compounds,’ ed. P. G. Sammes, Pergamon, Oxford, 1979.
D. M. G. Lloyd, Kern. Kozl., 1979,52, 13.
K. Nagarajan, Stud. Org. Chern. (Amsterdam),1979, 3, 317.
’ U. Eisner, Org. Compd. Sulphur, Selenium, Tellurium, 1979, 5 , 337.
M. Protiva, Pharmazie, 1979,34, 274.
’ G. J. Patriarche, J. C. Vire, C. A. Mairesse-Ducarmois, J. L. Vandenbalck, and G . D. Christian,
Bioelectrochern. Bioenerg., 1.979, 6, 147.
* M. Christ1 and H. Leininger, Tetrahedron Lett., 1979, 1553.
H. Prinzbach and H. Babsch, Heterocycles, 1978, 11, 113.
331
N Ts NTs
(3) (4)
(5) (6)
The reactive 1-thiacyclohept-4-yne (5) adds pyridine N-oxide at room tem-
perature to give (6), said to be the first 2H-azepine; at 145 "C the azepine ring
contracts to become a (2-pyridyl) substituent.'"
The first indeno[1,2-d]azepine (7), shown by n.m.r. to have a fully conjugated
14~-system,has been synthesized via the successive bromination-dehydro-
bromination of (81." The same group has developed two routes to (91, as a
possible precursor for the same system via dehydrogenation.12
(7) (8) R' = 0, R2 = H

(9) R' = H2, R2 = C02Et
0
Et%o Ph H
Ph Ph
X-Ray analysis has shown that the 'aromatic' azatropolone ring (11; R =
C 0 2 E t ) is, surprisingly, not planar, and it has chirality.I3 A general route to a
range of these interesting compounds is provided by the base-induced ring-
opening of (10) followed by dehydrogenation.I4
A new route to lactams (e.g. &-caprolactam,96%) by the reaction of l-nitroso-
and 1-nitro-1-halogeno-cycloalkanes, e.g. ( 1 2), with triphenylphosphine, or uia
the one-step reaction of the cycloalkanone oxime with halogen and
triphenylphosphine, goes via successive Perkov and Beckmann reactions,ls as,
shown in Scheme 1.
The photochemical ring-expansion of cyclic imides has been applied to various
N-(1-adamantyl)succinimides to produce systems with a 1-azepine-2,4-dione
10 A. Krebs, H. Colberg, U. Hopfner, H. Kimiing, and J. Odenthal, Heterocycles, 1979, 12, 1153.
'I M. Kimura, K. Satake, and S. Morosawa, Chetn. Lett., 1979, 807.
l2 M. Kimura and S. Morosawa, Bull. Chem. SOC.Jpn., 1979,52, 1437.
I' Y . Tsuda, M. Kaneda, T . Sano, Y. Horiguchi, and Y. Itaka, Heterocycles, 1979, 12, 1423.
l4 T. Sano, Y. Horiguchi, and Y. Tsuda, Heterocycles, 1979, 12, 1427.
I. Sakai, N. Kawabe, and M. Ohno, Bicll. Chem. Soc. Jpn., 1979, 52, 3381.
Seven-Membered Ring Systems 333
Reagents: i, PPh,; ii, H,O

Scheme 1
ring fused to the adamantane ring.16 It is reported that the formation of azepines
(15) rather than sulphonamides (13) in the addition of sulphonyl-nitrenes to
arenes is favoured when R is an electron-withdrawing group. This is taken to
support a polar cleavage of the azirine ring in (14) rather than an electrocyclic
0~ening.l~
The pyridoazepines (16; E = C0,Me) are formed by the reactions of 2-
alkoxy- or 2-acyloxy-methylpyridines with dimethyl acetylenedicarboxylate at
0 "C; on heating in benzene, they rearrange to (17).18
- ?;1'0;
80 "C
E'
E
(17)
Reactions of Monocyclic Azepines. The enolate anion (18) cyclizes to give (20)
via what is apparently a 5-endo-trig process (Baldwin disfavoured), so either this
'rule' applies with less rigour to the formatioq of bridged systems or an alternative
mechanism is operating - possibly prior tautomerization to (19) and a 5-exo-trig
cvclization. l 9
Me
A study of bishomoconjugative stabilization in 2-heterobicyclo[3.2.l]octa-

3,6-dienes has been made by looking at the Cope rearrangement equilibrium
between the diene form (21) and the imine form (22). The fact that the
diene form is more strongly favoured when R is electron-withdrawing than
when it is either electron-releasing or hydrogen argues against any special
'' M. Terashima, K. Ohkura, H. Okajima, and Y. Kanaoka, Heterocycles, 1978, 11, 265.
N. R. Ayyangar, M. V. Phatak, A. K. Purchit, and B. D. Tilak, Chem. Ind. (London), 1979, 853.
R. M. Acheson, J. D. Wallis, and J. Woollard, J. Chem. Soc., Perkin Trans. 1, 1979, 584.
19
B. Gregory, E. Bullock, and Teng-Song Chen, J. Chem. SOC.,Chem. Commun., 1979, 1070.
bishomoconjugative stabilization in (21).2"The 3H-azepine (23; X = H) can be

deprotonated at the 3-position by strong bases such as lithium di-isopropylamide
(LDA); the derived anion reacted with electrophiles to give 3-substituted deri-
vatives, e.g. (23; X = Me, SMe, or CH2Ph). However, the addition of esters,
e.g. methyl pivalate, gave pyridines (24), thought to be formed via (23; X =
COBu') as the primary product. If butyl-lithium is used as the base, not only
does it cause deprotonation but it also adds to the C-4-C-5 double-bond.*'
Caprolactam and other lactams may be N-alkylated under mild conditions,

using phase-transfer catalysis," and N-methylcaprolactam has been 3-methyl-
ated after deprotonation with ~ o d a m i d e .The
~ ~ catalytic hydrogenation of
2-(nitromethy1ene)perhydroazepine under acid conditions led to 2,5-bis-(5-
aminopenty1)pyrazine by rearrangement and d i m e r i ~ a t i o n . ~ ~
Fused Azepines.-Formation. A convenient route to benzazepinones (25) in
which the aryl ring has an electron-donating substituent (R) is provided by the
cyclization of y-(ary1)propyl isocyanates, using phosphorus oxychloride and
stannic The benzazepine- 1,3-dione (27) was synthesized by ring-
closure of (26) and hydrolysis of the 'chloroimide' (28) that was formed; irradi-
ation of (27) produced mainly dimers at the alkene bond.26
The recently reported cyclization of aryl halides uia intramolecular addition

of an organometallic complex to double bonds has been extended to the forma-
tion of seven-membered rings; e.g., the benzazepine (30) from o-chloroaniline
via treatment of ( 2 9 ) with MeMgBr and [NiC12(PPh3)2].27
*' P. Barraclough, S. Bilgic, and D. W. Young, Tetrahedron, 1979, 35, 91.
" J. W. Streef and H. C. van der Plas, Tetrahedron Lett., 1979, 2287.
'' M. Takahata, T. Hashizume, and T. Yamazaki, Heterocycles, 1979, 12, 1449.
23 T. Cuvigny, P. Hullot, P. Mulot, M. Larchevesque, and H. Normant, Can. J. Chern., 1979,57,1201.
24 Ciba-Geigy A.-G. Br. P. 1 525 672 (Chem. Abstr., 1979,91, 91 667).
2 5 T. Fushirni, H. Ikuta, H. Irie, K. Nakadachi, and S . Uyeo, Heterocycles, 1979, 12, 1311.
26 S. Puar and B. R. Vogt, Tetrahedron, 1978, 34, 2887.
27 M. Mori, S. Kudo, and Y. Ban, J. Chern. SOC.,Perkin Trans. 1, 1979, 771.
The cyclization of the (2)-isomer (31) with polyphosphoric acid (PPA) pro-
vides a new route to isoindolobenzazepines;some reductions and other reactions
of this compound have also been reported.28
The benzazepinone (33)is the major product in the addition of C,N-diphenyl-
nitrone to allene; it is formed from the primary adduct (32) by ring-opening
followed by biradical aromatic s u b ~ t i t u t i o n . ~ ~
(35)
Lactim ethers and thioethers are reactive substrates for 1,2-annelation by
bifunctional reagents, and a variety of novel systems in which benzazepines are
[a]-fused to five- and six-membered heterocyclic rings have been prepared in this
way; e.g., ( 3 5 ) from ( M ) . ~ "
Aromatic azides decompose via nitrene intermediates in the presence of
nucleophiles either to give ortho-substituted amines or to undergo ring-expansion
to azepines. In the photolytic and thermal decomposition of some azidoindoles,
the effect of the annelated pyrrole ring is strongly to favour the first reaction path,
for example to give (37)via (36). However, if the annelated ring is not aromatic,
as in (38),then azepines are obtained in good yield; these are the first tricyclic
systems to be obtained by this r o ~ t e . ~ '
Pyrroloazepines are of interest partly because of the antileukaemic activity of
some compounds that contain the lH-pyrrol0[2,l-b][3]benzazepine moiety.
The new 5H-pyrrolo[l,2- b][2]benzazepine system has been synthesized via the
base-induced cyclization of the key intermediate (39), followed by hydrolysis and
decarboxylation to give the parent nucleus.32
'' V. Scartoni, R. Fiaschi, S. Catalano, I. Morelli, and A. Marsili, J. Chem. SOC.,Perkin Trans. I, 1979,
1547.
29 J. J. Tufariello, Sk. A. Ali, and H. 0. Klingele, J. Org. Chem., 1979, 44, 4213.
'"K . Bhandori, V. Virmani, V. A. Murti, P. C. Jain, and N. Anand, Indian J. Chem., Sect. B, 1979,
17, 107.
31 E. F. V. Scriven, H. Suschitzky, D. R. Thomas, and R. F. Newton, J. Chem. Soc., Perkin Trans. I ,
1979, 53.
3 2 G. Stefancich, M. Artico, S. Massa, and S. Vomero, J. Heterocycl. Chem., 1979, 16, 1443.
H
t i36) (37)
Ac
CN
(39)
Reactions of Fused Azepines. The morphanthridene derivative (40) undergoes
an interesting rearrangement to (42) when treated with primary amines; the
reaction involves a transamidation which converts (4 1) into (42). Reversal, with
concurrent reduction of the carbonyl, is induced by lithium aluminium h ~ d r i d e . ~ ~
8
The diarylethylene-type double-bond in some dibenz-azepines and -0xepines can
be reduced conveniently and in high yield, using magnesium in methan01.~~
@ MeNH; ~~~ -
0 0 0
(40) (41) (42)
1,2-Diazepines.-Formation. The acid-catalysed reaction of some ap,y&nsat-
urated ketones (43) with tosylhydrazine provides an easy route to 3,4-dihydro-
1,2-diazepines (45); however, the ring-closure step is substituent-dependent, and
in some cases the tosylhydrazone (44) could not be c y ~ l i z e dThe
. ~ ~ base-induced
elimination of toluene-p-sulphinic acid from these dihydrodiazepines (45) pro-
vides the first route to 3H-1,2-diazepines [(46)/(47)].36This completes the range
of tautomers of the fully unsaturated system; interestingly, these 3H-tautomers
exist as diazepines, while the 5 H-tautomers, which are the only other ones to be
destabilized by an azo-group, favour the ring-contracted diazanorcaradiene
structure. These 3H-1,2-diazepines are also interesting in that the 1,5-
sigmatropic shifts of hydrogen which interconvert (46) and (47) are remarkably
fast compared with those of analogous cycloheptatrienes, so that the isomers
are not isolable at room temperature.
’’ R. Suss, Helc. Chim. Acta, 1979, 62, 1103.
34 J. A. Profitt and H. H . Ong, J. Org. Chem., 1979,44, 3972.
C. D. Anderson, P. N. Anderson, and J. T. Sharp, J. Chem. SOC.,Perkin Trans. 1, 1979, 1640.
16 C. D. Anderson, J. T. Sharp, and R. S . Strathdee, J. Chem. SOC.,Perkin Trans. I, 1979, 2209.
R'
R'
\
/c=x R2
R2 (45)
(43) x = 0
(44) X = NNHTs
A further study of the factors controlling periselectivity in the electrocycliz-
ation reactions of diazoalkenes that have extended conjugation has shown that
(49) undergoes both 1,5- and 1,7-closure, to give (48) and (50).37 The pyrazole
is kinetically favoured, but on further heating it rearranges to the diazepine,
probably uia a cycloreversion to the diazoalkene (49). The mode of cyclization
depends strongly on the size of the annelated ring; the cyclobexa-analogue of
(49) gives only the pyrazole (51), which does mi undergo ring-expansion to a
diazepine on heating but instead undergoes an unexpected sigmatropic shift of
the alkyl rather than the aryl group, to give (52). This failure of the phenyl group
to migrate is probably due to steric inhibition of the secondary interaction
between p-orbitals which normally stabilizes the transition state for migrations
of aryl groups.
A
Me
t
6rr
..___
+ -
C=N=N
I
8rr
--+
@ N
aN
(48) Me Me
(49) H
+
heat
K Ph
,N
y
\
Me Me
(51) (52)
Garanti and Zecchi have extended the range of their synthesis of 1,2-
benzodiazepines via 1,7-electrocyclization of the nitrile imines (54).Earlier work
used 1-chloro-hydrazones to produce diazepines bearing electron-withdrawing
substituents, but now the use of 1-nitro-hydrazones (53) allows the preparation
of unsubstituted and 3-alkyl-substituted diazepines ( 5 5 ) in moderate yield.38The
37
38
1433.
Ph
(53)
+
Et,N
L (54) -1 Ph
(55)
K. L. M. Stanley, J. Dingwall, J . T. Sharp, and T. W. Naisby, J. Chem. SOC.,Perkin Trans. I , 1979,
L. Garanti, G. Testoni, and G. Zecchi, Synthesis, 1979, 380.

3-unsubstituted diazepines, e.g. ( 5 5 ; R = H), were also produced (in low yield)
by the decarboxylation of the acids (56); however, the major reaction path led
to o-aminocinnamonitriles via ring-opening of the anion (57).39It had previously
been shown that the cyclization of analogues 9f (54) which have two substituents
at the alkene terminus goes predominantly via a 1,l-cycloaddition of the nitrile
imine to give cyclopropacinnolines, c.g. ( 5 8 ) , rather than via 1,7-electrocycliz-
ation. Now it has been reported that, in some cases, these products (58) can be
converted into diazepines by acid-catalysed cleavage of the cyclopropane ring,
as shown; this reaction, however, is strongly substituent-dependent, and in some
cases the alternative fission to give 1,4-dihydrocinnolines is f a ~ o u r e d . ~ '
(56) (57) RZ
H H
C0,Et AcOHI q C O z E t + q o 2 E t
C0,Et C0,Et C0,Et

Me AcO Me
Me
(58)
Some time ago the Streith ring-expansion of pyridiniurn N-imides was exten-
ded to the synthesis of 1H-l,2-benzodiazepines from quinoline N-imides. The
full report has now appeared of the further extension of this valuable synthetic
route to the preparation of the following previously unknown 1,2-diazepines,
annelated to heteroaromatic rings: pyrido[3,2-c]-, pyrido[2,3-c]-, thieno[2,3-c]-,
thieno[3,2-c]-, and furo[2,3-c]-lH-1,2-diazepines;e.g., (61) from (59),presum-
ably via (60).41A similar attempt to prepare pyrrolodiazepines was not success-
ful. These 1H-tautomers were converted into the 3H-1,2-diazepines by reduction
with lithium aluminium hydride and then dehydrogenation with 4-phenyl-
1,2,4-tria~oline-3,5-dione.~~
The 1-substituted isoquinoline N-imide (62), however, shows a new photoreac-

tion; instead of forming a 1,2-diazepine via closure at the 3-position, it cyclizes
to (63), which apparently rearranges further to (64) before opening to give a
lH-l,3-benzodiazepine (65).43 The 1-unsubstituted analogue, however, gives
39 L. Garanti and G . Zecchi, J. Heterocycl. Chem., 1979, 16, 1061.
40
L. Garanti and G . Zecchi, J. Chem. Soc., Perkin Trans. 1, 1979, 1195.
41
T. Tsuchiya, M. Enkaku, J. Kurita, and H. Sawanishi, Chem. Pharm. Bull., 1979, 27, 2183.
42 T. Tsuchiya, M. Enkaku, and H. Sawanishi, Chem. Pharm. Bull., 1979, 27, 2188.
43 T . Tsuchiya, M. Enkaku, J. Kurita, and H. Sawanishi, J. Chem. Soc., Chem. Conitnun., 1979, 534.
only 1-(ethoxycarbonylamino)isoquinoline. The photochemical behaviour of

N-imides of this general type is not yet easy to rationalize or predict; monocyclic
pyridine N-imides, whether 2- and/or 6-substituted or not, give only 1,2-
diazepines; quinoline N-imides give 1,2-diazepines, but only when 2-unsub-
stituted; and isoquinoline N-imides give only 1,3-diazepines, and then only when
1-substituted. However, the thieno[2,3-c]pyridine N-imide (66) reacted by both
routes, giving some lH-1,3-thieno[2,3-d]diazepine (67) but mostly 3H-2,3-
thieno[2,3-d]diazepine (68).44
The 4-vinyltetrahydropyridine N-imide (69) decomposed at 140 “C by two

pathways, i.e. a Stevens-type [1,2] rearrangement to give the diazepine (70) and
a [2,3] rearrangement with the double-bond in the ring to give (71). The
6-vinyl-analogue gave no diazepine and reacted mainly via a [2,3] rearrange-
Me
6 6
ment, to give 1,2-dia~acyclononadiene.~~
/ \-
NC0,Et
+
heat
N-NCO,Et
Me
+ (&
MeN’po,Et
(71)
(69) (70)
Reactions of 1,2-Diazepines. Unsymmetrically substituted 4H-1,2-diazepines
are not easily synthesized directly, because of the difficulty in obtaining the
required pyrylium salt precursors, but the 4-substituted compounds, e.g. (73),
are now accessible via deprotonation of (72), using LDA and TMEDA, and the
reaction of the anion with alkyl halides.46Some electrophiles, however, e.g. acetic
anhydride and chlorotrimethylsilane, gave N-substituted products, e.g. (74).
(72) (73) (74)

44 T. Tsuchiya, M. Enkaku, and H. Sawanishi, Heterocycles, 1979, 12, 1471.
45 T. Tsuchiya and H. Sashida, Heterocycles, 1979, 12,1453.
46 L. Bemi, M. T . Thomas, and V. Snieckus, Synthesis, 1979, 130.
Treatment of lH-l,2-benzodiazepines (75)with lead tetra-acetate (LTA) gives

the previously unknown 5H-tautomers (76) together with some 3-vinyl-
inda~oles.'~ The latter probably derive from the 3H-tautomer (77), as discussed
below (refs. 48 and 49). The SH-1,2-benzodiazepines are less stable than the 3H-
and 1H-tautomers and can be isomerized to the latter with base; they also readily
add acetic acid or methanol to give 1,4-adducts. Photolysis of (76) gives 3-
acetoxyindole, most likely via ( 7 ~ 2 s+ 7 ~ 2 sring-closure
) of the diazabutadiene
unit (cf.3H-1,2-diazepine and lH-2,3-benzodiazepines) and extrusion of RCN.
WR N"
H
(75)
z&R +[mR
NSN NN
:
(76) (77)
OAc 1
Several papers are concerned with the 1,2-diazepine -+ pyrazole ring-contrac-
tion [the reverse of the conversion of (48) into (50) described above]. In the full
paper on the thermal conversion of 3H-1,2-diazepines, e.g. (78), into pyrazoles,
it is proposed that the reaction involves a ring-contraction step to give (80)
followed by sequential vinyl and hydrogen migrations to give (81).Evidence from
the ratio of products derived from the equilibrated diazepines (46)/(47) points
to an electrocyclic ring-opening in the first step rather than a homolytic cleavage
of the azo-ally1 bond.48The analogous thermal and photochemical conversion of
3H-1,2-benzodiazepines into indazoles has been known for some time, but,
interestingly it has now been shown that whereas the thermal reaction of (82)
gives both ( E ) -and (2)-alkenyl-indazoles (83), the photochemical reaction gives
only the (E)-isomer. This is adduced as evidence for a homolytic cleavage-
recombination mechanism for the thermal reaction and probably a ( 7 ~ 2 s+ ~ 2 s )
concerted photochemical p r o c e ~ s . 'Thieno-
~ and pyrido-analogues of (82) also
showed a similar rearrangement, but some thienodiazepines also reacted via a
1,5-sigmatropic hydrogen shift, which preceded the ring-contraction" [cf. the
thermolysis of (46)/(47) discussed above].
-
MeQ
Me
(78) Me (79) -1
=N
(82) (83)
47 T. Tsuchiya and J . Kurita, J. Chem. SOC.,Chem. Commun., 1979, 803.
48 C. D. Anderson, J. T. Sharp, and R. S. Strathdee, J. Chem. SOC.,Perkin Trans. 1, 1979, 2730.
49 T. Tsuchiya and J. Kurita, Chem. Pharm. Brill., 1979, 27,2528.
Seven-Membered Ring Systems 34 1
The thermal and acid-catalysed ring-contractions of 1-acyl- 1,2-diazepines to

pyridine N-imides and/or 2-(acy1amino)pyridines is well known. Moore has now
reported a new reaction path in the thermolysis of (84), leading to the 1,3-
diazepine (85) in addition to a 6-benzamidopyridine. A stepwise conversion of
(84)into (85) is favoured, assisted by electron release from oxygen, rather than
a sigmatropic rearrangement5’ [cf. the formation of (65) described above].
I
COPh COPh
(84)
1
phfloMe
PhCONbN f- PhCON
Ph Me
QocoMe
(85)
The reaction of lH-1,2-benzodiazepines with singlet oxygen is much more
complex than that of its monocyclic analogues; whereas the latter give relatively
stable 47r + 277- adducts, the benzodiazepine (86) apparently reacts via ene
reactions to give the hydroperoxides (87) and (88), which decompose to give a
complex mixture of products. The N-methyl analogues of (86), however, gave
3-0xo-l,2-benzodiazepines.~~
1,3-Diazepines.-Use of the new reagent 2-(aminomethy1)phthalimide (89),

which is synthetically equivalent to the inaccessible 1,l-diaminornethane, pro-
vides a convenient entry to 2,4-benzodiazepines and may be valuable for the
preparation of other 1,3-diaza-hetero~ycles.~~
The 1,3-diazepine-2,5-dione (91) was obtained by cyclization of the di-
isocyanate (90) and subsequent deprotection with mercuric acetate; reduction
(89)
J. A. More, H. B. Yokelson, W. J. Freeman, and J. F. Blount, J. Org. Chetn., 1979, 44, 2683.
” T . Tsuchiya, K. Takayama, and J. Kurita, Chem. Pharm. Bull., 1979, 27, 2476.
52 R. F. Lauer and G. Zenchoff, J. Heterocycl. Chem., 1979,16, 339.
342 He teroc y c 1ic Chemistry
-
NCO
H H H
(90) (91) (92) (93)
Reagents: i, NaBH,; ii, BH,, iii, H,O,
Scheme 2
gave the alcohol (92), also obtained uia addition of diborane to (93)," as shown
in Scheme 2.
The reaction of various diacyl halides with NN-diaryl-acetamidines provides
a versatile route to 1,3-diazepines - either monocyclic or fused to various aro-
matic and heteroaromatic rings; e.g., (95) from (94).'4 3-Phenylimino-analogues
were similarly obtained, using 1,2,3-triphenylguanidine.One of these, i.e. (96).,
obtained by using 2-chloromethylbenzoy1 chloride, underwent a remarkable
rearrangement to (97) in polyphosphoric acid, as shown in Scheme 3.
I" H P h
P h N = CMe
(94)
<yRI @
L R2
NPh
(95) R' = CH2, R 2 = 0

(96) R' = NPh, R2 = H2
Reagents: i, o-C,H,(COCI),; ii, polyphosphoric acid
Iii
(97)
\
C=NPh
I
NHPh
Scheme 3
N-Substituted (o-isocyanopheny1)acetamides (98), prepared by the addition

of o-(1ithiomethyl)phenyl isocyanide to isocyanates, are cyclized by CuzOcatalyst
to give indoles and/or 1,3-benzodiazepin-4-ones(99); formation of the latter
is favoured by less bulky R groups."
1,4-Diazepines.-Forrnation. There is a report on the formation of the C = N

bond in 1,4-benzodiazepin-2-0nes and in 1,2-dihydropyrazin-2-0nes by the
intramolecular reaction of aldehyde groups or keto-groups with iminophos-
phoranes; the process had earlier been described in the patent literature.s6 1,4-
Benzodiazepin-2-ones have also been prepared from indoles by ozonolysir
followed by reductive cyclization with hydrazine h ~ d r a t e . 'A
~ new simple syn-
" V. E. Marquez, P. S. Liu, J. A. Kelley, and J. S. Driscoll, J. Org. Chem., 1980, 45, 485.
54 H. W. Heine, D. W. Ludovici, J. A. Pardoen, R. C. Weber, E. Bonsall, and K. R. Osterhout, J.
Org. Chem., 1979,44, 3843.
5 5 Y . Ito, K. Kobayashi, and T. Saegusa, Tetrahedron Lett., 1979, 1039.
', J. Ackrell, E. Galeazzi, and J. M. Muchowski, Can. J. Chem., 1979, 57, 2696.
57 H. Yarnamoto, S. Inaba, T. Okarnoto, T. Hirose, K. Ishizumi, M. Yarnarno, I. Maruyarna, K. Mori,
T. Kobayashi, and T. Izurni, Jpn. Kokai Tokkyo Koho 79 12 480 (Chem. Abstr., 1979,91,175 405).
thesis of 1,4-benzodiazepines, e.g. Diazepam, starts from secondary 2-amino-

benzhydrols rather than the usual 2-aminobenzophenones. These are obtain-
able in high yield by the specific ortho-hydroxybenzylation of secondary anilines;
e.g., (101) from
(100) (101)
A n efficientconversion of 5-chloro-N-methylisatoic anhydride and glycine into
7 -chloro- 1-methyl-3,4 -dihydro- 1H-l,4- benzodiazepine-2,5 -dione has been
described. Further reaction of its N-acetyl derivative with phenylmagnesium
chloride followed by treatment with hydroxylamine and then sodium bisulphite
provides another new synthesis of Diazepam in ca. 50% overall yield.59 The
1,4,5-benzotriazocinium salts (103), prepared by the cyclization of (2-chloro-
acetamido)benzophenone NN-dimethylhydrazones (102), reacted with sodium
methoxide in a Stevens-type reaction to give 3-amino-1,4-benzodiazepin-2-
ones (104) in good yield.6" The same products were also obtained by direct
treatment of (102) with base.
(102) (103) (104)

There is an increasing interest in the synthesis of fused diazepines with
potential anti-tumour activity. A new direct synthesis of pyrrolo[2,1 -c][ 1,4]-
benzodiazepin-5-ones, e.g. (105), has been developed en route to a complete
synthesis of the anti-tumour antibiotic sibiromycin.61 Two routes have been
devised to the novel pyrrolo[ 1,2-d][ 1,4]benzodiazepin-6-one system, but mem-
bers of this series were inactive as sedative, depressive, or myorelaxant agents.62
(105)
The new indolo[l,7-ab][1,5]benzodiazepine system (107) has been constructed
from (106).h3
Further variations have been reported on the synthesis of pyrrolo-
[1,2-a]thieno[3,2-f]-1,4-diazepin-4-ones,giving the 6-alk0xy-~~"and the
58 T. Sugasawa, M. Adachi, T. Toyoda, and K. Sasakura, J. Heterocycl. Chem., 1979, 16,445.
59 M. Gates, J. Org. Chem., 1980, 45, 1675.
6o H. Natsugari, K. Meguro, and Y. Kuwada, Chem. Pharm. Bull., 1979,27, 2084.
61 K. A. Parker and T. H. Fedynyshyn, Tetrahedron Lett., 1979, 1657.
62 E. Aiello, G. Dattolo, G. Cirrincione, S. Plescia, and G. Daidone, J. Heterocycl. Chem., 1979, 16,
209.
63 E. J. Glarnkowski and J. M. Fortunato, J. Heterocycl. Chem., 1979, 16, 865.
64 ( a )S. Rault, M. Cugnon d e Skvricourt, and M. Robba, Heterocycles, 1979,12,1009; (6) Tetrahedron
Lett., 1979, 643.
344 He teroc yc lic Chemistry
(106) (107)
6-(2-oxoalkyl)-derivatives.64hThe reaction of the anions of malononitrile or
cyanamide with 2-substituted 1,3-oxathiolium cations (108) gave the amino-
ketones (109) and (110), which are key precursors to the synthesis of thieno-
and thiazolo-[ 1 , 4 ] d i a ~ e p i n e s . ~ ~
R
Reactions a n d Properties of 1,4-Diuzepines. 2-Amino-5-phenyl-3H-1,4-benzo-

diazepines were converted into their 1-oxides, e.g. (1111, by rn-chloroper-
oxybenzoic acid; when these oxides reacted with phosgene in the presence of
imidazoles they underwent an interesting rearrangement to give the 3-imidazolyl
derivatives, e.g. (113), apparently via primary formation of the unstable com-
pound (112). Treatment of (111) with acetic anhydride gave the 2-acetamido-3-
0x0-derivative."
0
? NH,
Ph Ph Ph
(111) (112) (113)
1,4-Benzodiazepin-2-onescan be hydroxylated in the 3-position uia the
two-step process shown in Scheme 4; e.g. (114) to (116). The 3-acetoxylated
intermediate (115) can also be prepared via bromination with NBS and reaction
with sodium acetate in sit^.^^
H o H o H O
Ph Ph Ph
(1 14) (115) (116)
Reagents: i, LTA, I,, AcOH; ii, MeOH, CH,Cl,, NaOMe
Scheme 4
65 K. Hirai, H. Sugimoto, and T. Ishiba, J. O r g . Chem., 1980, 45, 253.
66 H. Natsugari, K. Meguro, and Y. Kuwada, Chem. Pharm. Bull., 1979, 27, 2608.
'' T. Kovat, M. Oklobdiija, V. S h j i c , and F. Kaifei, J. Heterocycl. Chem., 1979, 16, 1449.
Oxazepam (116) can be converted into a range of 3-(disubstituted-amino)
derivatives, in moderate yield, by its reaction with the appropriate 2-amino-4,5 -
dihydr0-1,3,2-dioxaphosphole.~~ A direct route to the 3-amino-derivatives has
also been reported.69 1,3-Dihydro-2H-1,4-benzodiazepin-2-ones react with
most isocyanates to give the 1-carbamoyl derivative; however, (114), on reaction
with trichloroacetyl isocyanate and subsequent hydrolysis, gave the 3-amido-
' latter has been converted into a range of 3 - e ~ t e r s . Continuing
d e r i ~ a t i v e . ~The ~'
work on the electrolytic reduction of 2,3-dihydro-l,4-diazepiniumsalts has
shown that the NN-dibenzyl-6-phenyl-compoundgives a diazepine dimer and
an unexpected rearrangement product, which is 1,4-di-imidazolidinyl-
b~tadiene.~~
N.m.r. analysis of the conformational preferences of some 1,4-
benzodiazepines by use of lanthanide shift reagents shows that Diazepam exists
in a boat conformation that is very similar to its structure in the solid state, while
the N-desmethyl analogue shows a conformational equilibrium between two
pseudo-boat form^.'^ The relationship between conformation in solution and
biological activity has been discussed. A similar study on the (3S)-methyl
analogue of the latter shows that it adopts the expected quasi-boat conformation
with the C(3)-methyl group in a quasi-equatorial position.74 Conformational
studies by n.m.r. have also been carried out on 5,7,7-trimethyl-2,3,6,7-
tetrahydro-lH-1,4-dia~epine~~ and on the hexahydro-1,4-diazepine A
d.n.m.r.* determination of the kinetic and thermodynamic parameters for
conformational inversion of 5-methyl-1,2-dihydro-3H-1,4-diazepin-2-ones has
shown that the inversion barrier is ca. 2.4 kcal mol-' lower than for the 5-phenyl
analogues; this parallels similar observations on other b e n z o d i a z e p i n e ~ . ~ ~
Determinations of crystal structures have confirmed properties previously
inferred from other data, i.e. (i) that chlorodiazepoxide hydrochloride
(Librium) is protonated on N-l,78 and (ii) that 2,3-dihydro-1,4-diazepinium
perchlorates have a delocalized unsaturated system, which is responsible for
their quasi-aromatic proper tie^.^^ Mass spectral rearrangement and fragmenta-
tion pathways have been elucidated for several 5-phenyl-l,4-benzodiazepine
derivatives.80
* d.n.m.r. = dynamic n.m.r.
68 F. Gatta, M. R. del Giudice, and G . Settimj, Synthesis, 1979, 718.
69 Z. I. Zhilina, A. V. Bogatskii, S. A. Andronati, and N. I. Danilina, Khim. Geterotsikl. Soedin., 1979,
545 (Chem. Abstr., 1979,91, 157 698).
7u R. B. Moffet and B. V. Kamdar, J. Heterocycl. Chem., 1979, 16, 793.
7 1 H. Demarne and J. C. Molimard, Ger. Offen. 2 900 017 (Chem. Abstr., 1979,91, 157 776).
7 2 D. Lloyd, C. A. Vincent, D. J. Walton, J-P. Declercq, G. Germain, and M. Van Meerssche, Bull.
Soc. Chim. Belg., 1979, 88, 113.

73 G. Romeo, M. C. Aversa, P. Giannetto, M. G. Vigorita, and P. Ficarra, Org. M a p . Reson., 1979,
12,593.
74 V. S h j i c , A. Lisini, A. Sega, T. Kova?, and F. Kaifei, J. Heterocycl. Chem., 1979, 16, 757.
7 5 S. P. Kasprzyk and S. Szymanski, Pol. J. Chem., 1979, 53, 525.

76 M. Majchrzak, A. Kotelko, and R. Guryn, Pol. J. Chem., 1979, 53, 2135.
77 A. V. Bogatskii, S. A. Andronati, V. I. Minkin, L. E. Nivorozhkin, V. S. Yur'eva, T. I. Korotenko,
and Yu. S. Katrenko, Vopr. Stereokhim., 1978, 7, 3 (Chem. Abstr., 1979, 91, 38 780).
'' C. Herrnstadt, D. Mootz, H. Wunderlich, and H. Mohrle, J. Chem. Soc., Perkin Trans. 2, 1979,735.
'' G. Ferguson, W. C. Marsh, D. Lloyd, and D. R. Marshall, J . Chem. SOC.,Perkin Trans. 2, 1980,
74.
80
F. M. Vane, W. Benz, and U. Rapp, Org. Mass Spectrom., 1979, 14, 154, 233.
4 Oxepins and Dioxepins
0xepins.-Formation. A new route to benzoxepins from (2)-styryl-oxirans, e.g.
of (119) from (117), is of the same general type as the route to benzodiazepines
from diazoalkanes [(49) + (50), described above]. Thermal cleavage of the
oxiran generates the extended carbonyl ylide (1IS), which undergoes 87r elec-
trocyclization followed by a [1,5] hydrogen shift to give (119); interestingly, no
competing 677 cyclization was observed in this reaction.81
+
C02Et
Ph
/
' Ph/
Ph
(1 17) (118) (119)
Some nice chemistry has been reported on the Cope and retro-Claisen re-
arrangements of alkynyl three-membered rings. The gas-phase thermolysis of
cis-ethynyl(vinyl)oxirans, e.g. (120), gave cyclopropanecarboxaldehydes (122)
via the strained intermediate (121). However, in liquid-phase thermolysis, both
(120) and (122) gave dihydro-oxepins or phenols, via 1,3 hydrogen shifts in
(121); for example, (121; R' = Bun, R2 = H) gave (123), while (121; R1 = H,
R2 = Ph) gave (124), which was converted into 4-hydroxybiphenyl uia (125).82
R'
.H
heat
--b
- (121) J
In an extension of earlier work on smaller ring systems, it has been shown that
the reaction of the phenolic ketones (126) with sulphur ylides gives benzoxepin
derivatives (128) in generally good yield; chromans (129) were also formed, in a
minor reaction path involving ring-opening of the oxyanion of the epoxide
formed from (127).83The major and minor products can readily be distinguished
by their mass spectra, because skeletal rearrangements to common structures do
not occur.84
W. Eberbach, B. Burchardt, and U. Trostrnann, Tetrahedron Lett., 1979,4049.
82 F. Bourelle-Wargnier, M. Vincent, and J. Chuche, J. Org. Chem., 1980, 45, 428; J. Chem. SOC.,
Chem. Commun., 1979, 584.
'' P. Bravo, C. Ticozzi, G. Fronza, R. Bernardi, and D. Maggi, Gazz. Chim. Ztal., 1979, 137.
84 A. Seva, P. Traldi, P. Bravo, and C . Ticozzi, Ann. Chim. (Rome),1979, 69, 53.
-
+ oH,C=SOMe2
~ ~ ~ 2 J 2 C R
(127)
The acid-promoted rearrangement of the diazo-compound (130), prepared by

the reaction of ethyl lithiodiazoacetate with isochroman-4-one, gave the new
2-benzoxepin system (131); a similar sequence, starting with chroman-4-one,
gave the analogous 1-benzoxepin. Both were de-ethoxycarbonylated by a mild
alumina-assisted procedure.’’
L J U )
(131)
The product of the oxidation of 5,5’-dimethoxy-3,3’-di-t-butylbiphenyl-2,2’-
diol with lead tetra-acetate, originally formulated as a benzoxet, has now been
shown to be (133), which is formed via valence tautomerization of the
diphenoquinone (132).86
The cyclic carbonate (134), produced by the addition of vinylene carbonate to
phencyclone, loses CO, on photolysis and rearranges to (135), which is the first
example of a phenanthro [9,lO- b Ioxepin. 87 0
Me0 OMe
OAc
(132) (133)
Ph
(135)
R. Pellicciari, B. Natalini, M. Taddei, A. Ricci, G. A. Bistocchi, and G. de Meo, J. Chem. Res. ( S ) ,

1979,142.
F. R. Hewgill, D. G. Hewitt, G. B. Howie, C. L. Raston, R. J. Webb, and A. H. White, J. Chem.
Soc., Perkin Truns. 1, 1979, 290; see also H-D. Becker, K. Gustafsson, C. L. Raston, and A. H.
White, Aust. J. Chem., 1979,32, 1931, and F. R. Hewgill, C. L. Raston, and A. H. White, ibid., p.
881.
E. A. Harrison and H. L. Ammon, J. Org. Chem., 1980, 45, 943.
Bridged saturated oxepin derivatives can be produced by oxyselenation of

cyclo-octadienes and 5-hydroxycyclo-octenes, e.g. (136), via transannrilar attack
of oxygen on a first-formed episelenium ion; the product ratio is solvent-
dependent.88
(136) R = H or Me
Oxepan and other oxygen- or nitrogen-containing saturated heterocycles can
be prepared in high yield by the dehydrative coupling of aw-diols or amino-
alcohols, using diethyl azodicarboxylate and triphenylph~sphine.~’
The syntheti-
cally useful oxepin-2,7-diones (muconic acid anhydrides) can be conveniently
prepared by the oxidation of ortho-benzoquinones with m-chloroperoxybenzoic
acid.”
Properties and Reactions of Oxepins. Theoretical work on the valence isomeriz-
ation between oxepin and benzene oxide shows a surprising failure of both
MIND0/3 and the ab initio method wholly to reproduce the known effects of
mono- and di-substitution with methyl groups on the position of the equilibrium;
for example, MIND0/3 successfully ‘predicted’ the effect of methylation at the
2- and 3- but not at the 4-position, and an ab initio (STO-3G) method did less
well. Relating the observed effects to the ability of the methyl group to stabilize
by hyperconjugative delocalization seems to provide a better ‘rationalization.’ A
number of predictions (MIND0/3) have been made of the effects of other
.rr-donor and n-acceptor substituents; some of these compounds would appear
to provide a considerable synthetic challenge.” The photochemistry of the
valence tautomer (137) of perfluoromethylated oxepin shows some interesting
transformations; thus irradiation through silica caused quantitative conversion
into (138) and (139), and further irradiation through Pyrex gave only the oxeten
(140). Thermal decomposition of the oxeten gave (139) in quantitative yield,
R R, R R
R
-I
K
R R
(137) 9
heat I
R = CF3 RpR+xR
R
1140)
” S. Uemura, A. Toshimitsu, T. Aoai, and M. Okano, J. Chem. Suc., Chem. Commun., 1979 610.
89 J. T. Carlock and M. P. Mack, Tetrahedron Lett., 1978, 5153.
9o T. R. Demmin and M. M. RogiC., J. Org. Chem., 1980, 45, 1153.
D. M. Hayes, S. D. Nelson, W. A. Garland, and P. A. Kollman, J. A m . Chem. SOC.,1980,102, 2 5 5 .
while only (138) had the correct stereochemistry for thermal conversion back
into (137).92
Some careful chemistry has delineated the complex dependency of the photo-
chemical pathways open to (141) on solvents, sensitizers, acids, and temperature.
The primary sensitized photoproduct is (142), produced via a 1,5 phenyl shift;
in the absence of acid this goes on to give (144) by a di-7r-methane rearrangement.
However, when acid is present ( e . g . in old methylene chloride), (142) preferen-
tially ring-contracts to give the styryl-furanones (143). Compound (142) was
separately synthesized for this mechanistic study and found to undergo a rapid
thermal [1,5] hydrogen shift (above 4°C) to give (145); both (142) and (145)
underwent the expected photochemical conversions into fused c y c l ~ b u t e n e s . ~ ~
(145)
(144)
Dioxepins.-The photolytic decomposition of the epoxide (147) goes via several
reaction paths, but in pentane the major product is the dioxepin (148), formed
by cleavage of the yS-bond and biradical cyclization of the delocalized ally1
hv
+
(147)
1,3-Dioxepans and 4,7-dehydro-l,3-dioxepinscan be conveniently prepared
by allowing the appropriate diol HOCH2-A-CH20H (A = CH2CH2 or
CH=CH) to react with ketones in the presence of the dimethylformamide-
methyl sulphate a d d ~ c t . ~
2-Halogenomethyl-
' 1,3-dioxepans have also been pre-
pared from the first of the above diols (A = CH2CH2) by its reaction, for
example, with bromoacetaldehyde diethyl acetal in the presence of acid.96The
'* Y. Kobayashi, Y. Hanzawa, W. Miyashita, T. Kashiwagi, T. Nakano, and I. Kumadaki, J. A m .
Chem. Soc., 1979, 101,6445.
93 N. Hoshi, H. Hagiwara, and H. Uda, Chem. Lett., 1979,1291 and 1295; Kogugaku Toronkai Koen
Yoshishu, 1979, 14 (Chem. Abstr., 1980,92, 214 634).
94 B. Frei, G. de Weck, K. Miillen, H. R. Wolf, and 0.Jeger, Helv. Chim. Actu, 1979, 62, 5 5 3 .
95 W. Kantlehner and H.-D. Gutbrod, Synthesis, 1979,975.
96 N. G. Luk'yanenko, G. L. Kamalov, A. V. Bogatskii, and S. A. Kotlyar, Khim. Prom-.st., Ser.: Reakt.
Osobo Chist. Vahchestva, 1979, 28 (Chem. Abstr., 1979,91, 123 719).
0
HCIO,
i149)
oxidative ring-opening of chromanones, e.g. (149),and subsequent lactonization
provides a route to 1,5-benzodioxepin-2-0nes(150).97
The effect of the nature and size of 2-substituents on the preferred conforma-
tion of 1,3-dioxepans has been studied by i.r. and dipole-moment measure-
~ ~ . ~ ~3 n.m.r. spectroscopy provides a useful way to distinguish
m e n t ~ .Carbon-1
between ring sizes 5-7 of cyclic acetals, using both the chemical shift of the
acetal carbon and the coupling constant with its attached proton.100
5 Thiepins and Dithiepins

Thiepins.-Monocyclic thiepins are generally thermally unstable because of their
propensity to extrude sulphur via valence tautomerization to the thianor-
caradiene form, e.g. (153). This conversion is, however, disfavoured by bulky
groups at the 2- and 7-positions, which sterically destabilize (153).Thus although
(152; R = Prl) readily extruded sulphur at -70°C, it has now been reported
that (152; R = But) is remarkably stable ( t l I 2= 7.1 h at 131 'C).'O1 This com-
pound was prepared from a 2,6-di-t-butyl-4-methylthiopyrylium salt by treat-
ment with ethyl lithiodiazoacetate to give (15l), followed by ring-expansion,
using a palladium catalyst.
Using another approach, the longevity of thiepin has been increased by ester
substitution. The reaction of 3-(1 -pyrrolidinyl)thiophens with dimethyl acety-
lenedicarboxylate (DMAD) is known to give the compounds (154), which are
bicyclic isomers of thiepin (155). In acetonitrile, this species (or the thianor-
caradiene) survives long enough to be intercepted by a further molecule of
DMAD before desulphurization can occur to give sulphur-containing products
derived from (156).'02
" F. Eiden and C. Schmiz, Arch. Pharm. (Weinheim, Ger.), 1979, 312, 741.
" B. A. Arbuzov, E. N. Klimovitskii, A. B. Remizov, and G . N. Sergeeva, Izu. A k a d . Nauk SSSR,
Ser. Khim.,1980, 290, (Chem. Abstr., 1980,92, 214 804).
y9 B. A. Arbuzov, 0. A. Erastov, S. Sh. Khefagurova, and T. A. Zyablikova, Izu. A k a d . Nauk SSSR,
Ser. Khim., 1979, 2136 (Chem. Abstr., 1980,92, 58 072).
loo T. B. Grindley and V. Gulasekharam, Carbahydr. Res., 1979, 74, 7.
lo' K. Nishino, S. Yano, Y. Kohashi, K. Yamamoto, and I. Murata, J. A m . Chem. SOC.,1979, 101,
5059 (see also Chem. Abstr., 1980, 92, 180 972).
D. N. Reinhoudt, G. Okay, W. P. Trompenaars, S. Harkema, D. M. W. van den Ham, and G. J.
van Hummel, Tetrahedron Lett., 1979, 1529.
(154)
E = COzMe
E
(156)
The reaction of the complex (157) with divinyl sulphone gave the dihydro-
thiepin 1,l-dioxide (159) instead of the expected triene (158); the latter is
probably the primary product, and is converted into (159) by an intramolecular
Diels-Alder reaction and subsequent isomerizations. lo3
The anions derived from (160) and its enol ether were acylated and alkylated
to give 1-benzothiepins, e.g. (161); thermal desulphurization then gave the
expected naphthalene^."^ 1-Benzothiepin 1-oxides (162) were prepared by two
routes, and were decomposed at 30 or 50 "C to give naphthalenes by loss of SO;
the 1,l-dioxides that were produced by further oxidation of (162) were much
more thermally
Bohmes' group has published several papers on the chemistry of 3-
benzothiepin-1-ones and their sulphones. These compounds (163a) were depro-
tonated, e.g. with sodium hydride in DMF, and then allowed to react with a
R'
Me 0 R2
R' R2
(163) a; H H
b; H CSNHR3
-
S
//
c; H -C
's-
I S-
-0
/
(162) d; =C
\
S-
e; =CHR3
f; H CONHR3
'03 U. Khand and P. L. Pauson, Heterocycles, 1978, 11, 59.
'04 H. Hofmann and R. Heidrich, Z . Naturforsch., Teil B,1979, 34, 1145.
H. Hofmann and H. Gaabe, Chem. Ber., 1979,112,781.
variety of alkylating, acylating, and arylating reagents to give either mono- or
di-substitution at C-2, or 0-substitution (to give enol ethers), depending on the
nature of the electrophile.'06" The carbanions also react with isothiocyanates to
give the thiocarbamoyl derivatives (163b) and with carbon disulphide to give
mono- or di-anions of type (163c) and (163d). Some chemistry of these products
has also been described.lo6'
The oximes of (163a) have also been prepared, and they underwent Beckmann
rearrangements to give 4 , l -benzothiazocine derivatives. The reaction of (163a)
with secondary amines gave enamines.'"6' Aldol condensations at C-2 gave
ap-unsaturated ketones (163e), and the reaction of (163a) with isocyanates gave
2-carboxamides ( 163f).106d
Dithiepins.-There are two new variations o n the preparation of dithiepins by
migration of a thio-group in 1,3-dithians. Treatment of the 1,3-dithian-2-y1-
methanols (164; R = C 0 2 M e or H) with methanesulphonyl chloride gave the
1,4-dithiepin (165), presumably by ring-expansion of the sulphonate ester. '()'
Another example is provided by the oxidation of the 2-ethylidene-1,3-dithian

(166) with lead tetra-acetate; the yields if R = alkyl or aralkyl varied between
34 and 67%, but if R = phenyl only (167) was produced, and not the thiepin
enol acetate, as stated earlier by another group.lo8
MeO@HR 1 1 --+
PhCH,O \ OH
Dynamic n.m.r. studies on 2,4-benzodithiepiris have revealed striking

differences in conformational properties from their oxygen analogues in that
twist-boat structures are more strongly disfavoured; the results have been
discussed in terms of anomeric and steric effects.'"' The same method has also
been used in conformational studies on a range of seven-membered dithia-
spirans.' l o
H. Bohrne and R. Malcherek, Arch. Pharm. (Weinheirn, Ger.),1979,312, ( a )p. 653; ( 6 )p. 81 ; ( c )
p. 648; ( d ) p. 15.
lo' P. M. Weintraub, J. Heterocycl. Chern., 1979, 16, 1081.
"" K . Hiroi and S. Sato, Chem. Lett., 1979, 923.
I"' F. Sauriol-Lord and M. St.-Jacques, Can. J. Chem., 1979, 57, 3221.
'I" S. Smolihski and B. Rys, Monatsh. Chern., 1979, 110, 279.
6 Systems containing Two Different Heteroatoms
Oxazepines and Thiazepines.-The irradiation of quinoline N-oxide (168) has
been assumed to give the 3,l-benzoxazepine (169) as the primary product, but
in earlier work only the hydrolysis products N-formylindole and N-formyl-2-
hydroxyindoline were obtained. In a re-investigation of the photolysis, carried
out under scrupulously anhydrous conditions, the parent benzoxazepine has been
obtained for the first time. Under the same conditions, isoquinoline N-oxide gave
the non-isolable 1,3-benzoxazepine (170), which could be identified spectro-
scopically in dilute solution and trapped by the addition of amines, but which
polymerized when concentrated.' l 1
An analogous reaction forms the key step in a direct and versatile route to
4-substituted indoles from quinoline N-oxides. Irradiation of the latter gave (171;
X = H), which was hydrolysed by chromatography on silica to give the indolinol
(172); this was transformed into (173)."* The benzoxazepines (171) are stable
solids when X = CN, but they rearranged if irradiated (254nm) to give the
3-formylindole (174) [cf. the analogous reactions of diazepines and oxepines
described above].
Me0,C
NaHCO, \
N
CHO H
(171) (172) (173)
IY
H 1
(174) 0
1,2-Oxazepines have previously been suggested as unstable intermediates in

the photolysis of acridine N-oxide and related N-oxides; now two examples, (175;
R = CN) and (175; R = Cl), have been isolated for the first time.113As predic-
ted, they are unstable and undergo a variety of isomerization reactions in the
dark and under mild conditions. The novel cyclic sulphilimine (176) ring-expands
when boiled in xylene to give the dibenzothiazepine (177) in moderate (26%)
~ie1d.l'~
Earlier work on the use of C,N-dilithiated intermediates in the synthesis of
phenanthridenes has now been extended to the seven-membered dibenzo-
A. Albini, G. F. Bettinetti, and G. Minoli, Tetrahedron Lett., 1979, 3761.
'I2 C. Kaneko, A. Yamamoto, and M. Hashiba, Chem. Pharm. Bull., 1979, 27, 946.
S. Yamada and C. Kaneko, Tetrahedron, 1979, 35, 1273.
'I4 M. Hori, T. Kataoka, H. Shimizu, and K. Matsuo, Tetrahedron Lett., 1979, 3969.
8- GH
heat
\ +,N-
Me ' S J
H (179)
(178) Y = 0, S, or N H
systems (179), which were prepared by treatment of (178) with dimethylform-
amide.' l 5
P-Thiolamine derivatives of substituted aromatic acids (180) are more difficult
to cyclize than their hydroxy-analogues, but with dicyclohexylcarbodi-imide they
undergo conversion either into (18 1; R = H) or into mixtures of (181; R = Me)
and (182; R = Me) in good yield, the latter probably via a Smiles rearrangement
which precedes cyclization. ' I 6 The chromene derivative (183) reacted rapidly
with TCNE at room temperature to give the benzoxazepine (185) via a
stabilized zwitterionic intermediate which ring-closed to give (184) and was then
converted into (185) by a Cope rearrangement.'17
The reactions of 3-formylchrornones, e.g. (186), with various ortho-substituted

anilines (Y = S, 0, or NH) provide a high-yielding route to the fused benzo-
pyrano-compounds (187)."' Various substituted 2,3-dihydro-l,4-benzox-
azepin-5(4H)-one-7-acetic acid esters were prepared by the Schmidt reactions
of chromanone derivatives.
'15 N. S. Narasimhan and P. S . Chandrachood, Synthesis, 1979, 589.
E . Y. Chan, R. G . Crampton, and L. B. Clapp, Phosphorus Sulfur, 1979,7,41.
'I7 H. Yamaoka, 1 . Yamada, S. Ono, a n d T . Hanafusa, Chem. Lett., 1979, 523.
'
A. 0. Fitton, P. G. Houghton, and H. Suschitzky, Synthesis, 1979, 337.
D . R. Shridhar, C. R. Sarma, R. R. Krishna, and Y . P. Sachdeva, Indian J. Chem., Sect. B, 1979,
17, 155.
pjjHo+H;:Q -& - - y I- \
(186)
(187) Y = S, 0, or NH
The base-induced cyclization of the chloro-ketones (188) provides a route to
clavulanic acid analogues (189), but in some cases an alternative enolate displace-
ment, involving the ester carboxyl group, gives the surprisingly stable
oxazepinones, e.g. (190), as the major products.120
The new heterocyclic system (192) is produced in good yield by base-induced

7-em-dig cyclization in (191); the major by-product is an s-triazolo[2,3-e]-
[ l,S]benzoxazonine, formed via the competing but apparently less favoured
8-endo-dig closure.121The novel tricyclic systems (193) were produced by the
ring-closures shown, mediated by polyphosphoric acid; both lactams were readily
chlorinated in the 3 - p o ~ i t i o n . ~ ~ ~
Comparison of their photoelectron spectra shows that (194; Y = CH) are
more planar than when Y = N, but correlations with U.V.data show that the latter
become more nearly planar in
SEt
OCH,CGCH 0
(194) X = CH2, 0, S, NMe, or CO

0
Y = CHorN
(193) X = 0 or S
Other Systems.-An oxaselenepan (195) is formed as the primary product by

intramolecular oxyselenation in the reaction of diallyl ether with potassium
selenocyanate in methanol, in the presence of copper(I1) ch10ride.l~~
A range of
I*" P. M. Bentley, G. Brooks, M. L. Gilpin, E. Hunt, and I. I. Zomaya, Tetrahedron Lerr., 1979, 391.
'*' H. Moskowitz, A.Mignot, and M. Miocque, J. Heterocycl. Chem., 1979, 16, 1077.
122
J. B. Press, N. H. Eudy, and S . R. Safir, J. Org. Chem., 1980, 45, 497.
lZ3 L. Klasinc, A.Sabljic, and V. Siinjic, Abh. A k a d . Wiss.DDR, Abt. Math., Nnturwiss., Tech., 1978,
227 (Chem. Abstr., 1979,91, 56 188).
A. Toshimitsu, S. Uemura, and M. Okano, J. Chem. SOC., Perkin Trans. 1, 1979, 1206.
silicon-containing seven-membered heterocycles (197; X = 0, NEt,, SO2, or

CH2)have been prepared by the ring-expansion of (196); the reaction is probably
initiated by attack of F- at silicon.125
Se C N
QXD
' - /
si
\
/
(195)
F-. oxp
' 'si / \
Me C%C1 Me F
(196) X = 0, NEt, SO2, or CH2 (197)
ULIL
0273 7 Systems containing Three Heteroatoms

Methylation of the sulphimide (198; R = CH2Ph) with trimethyloxonium
fluoroborate gave the first example of the 1,3,5-benzothiadiazepinering system,
probably uia a Pummerer-type rearrangement of (199). The rearrangement did
not take place, however, €or R = M e or when alkyl halides were used as
alkylating agents. The product (200)rearranged readily in acid to give a benzo-
thiazoline. 126
H
a N ;+N-
\ Y o
R
(198) (199)
The 1,3,4-benzothiadiazepine(201 ; R = H, X = NCONH2),prepared by the
reaction of o-thiocyanatoacetophenone with semicarbazide, decomposed at
200 "C in diethylene glycol to give the benzisothiazole (202;R = H).Similarly,
(201;R = NH2, X = 0)gave (202;R = NH2) on heating with polyphosphoric
The 1,3,5-thiadiazepine-4,6-diones(203)were formed in good yield as
2 : 1 adducts of trimethylsilyl cyanide and thiobenzoyl isocyanate.128 A new
S
'25 J . Y . Carey and V. H. T. Chang, J. Organomet. Chem., 1979, 174,C15; see also B. L. Solz and
J. Y. Carey, ibid., 1979, 171,291.
126 T. L. Gilchrist, C. W. Rees, and I. W. Southon, J. Chem. Res. ( S ) ,1979, 214.
K. Clarke, B. Gleadhill, and R. M. Scrowston, J. Chem. Res. ( S ) , 1979, 395.
128 0.Tsuge and S. Urano, Heterocycles, 1979, 12, 1319.
synthesis of 1,2,5-benzothiadiazepine1,l-dioxides, e . g . (205)and (206), involves

the reaction of 2-nitrobenzenesulphonyl chloride with w-aminoacetophenone to
a
give (204), followed by reductive c y ~ l i z a t i o n . ' ~ ~
so2 N HC H ,COPh
NO,
H
(204) (205) (206)
A number of substituted 1,3,4-benzotriazepin-5-ones(208) have been synthe-
sized both by the cyclodesulphurization of the thiosemicarbazides (207) and by
the reaction of (209)with isothiocyanates in the presence of dicyclohexylcarbodi-
dGiN
0H
imide (DCDD).'" The benzotriazepinethiones (2 11) were prepared via the
acid-catalysed cyclization of (2 10).l'' RNCS
+
lDcDD
ocoNHN:
\ DCDD CONHNH,
CNHR --+
NH2 s \ N A NH2
NHR (209)
(207
A metalloid template has been used in the synthesis of some triazepinones and
triazepinethiones; thus, for example, the reaction of acyclic diamines with
dimethylsilicon isocyanate gave (212); after its reaction with thiocarbonyl di-
imidazole and subsequent hydrolytic removal of the silicon template, (212) gave
(213).132Aminohydroxy-1,2,4-triazepines(214; R = H or Me) have been pre-
pared in high yield by the addition of aminoguanidine to acrylonitrile and related
unsaturated Condensation of P-keto-esters with 1,2-diarnino-
imidazoles gave mainly imidazotriazepinones, e.g. (215), but with P-diketones
(212) (213) (214)

0. Migliara, S. Petruso, and V. Sprio, J. Heterocycl. Chem., 1979, 16,835.
I3O A. Mohsen, M. E. Omar, and F. A. Ashour, J. Heterocycl. Chem., 1979, 16,1435.
13' P. Richter and K. Gerisch, Pharmazie, 1979, 34, 847.
132 A. Shanzer, Angew. Chem., Int. Ed. Engl., 1980, 19, 327.
13' K. Shirai, T. Kumamoto, Y. Kabayashi, and T. Ri, Jpn. Kokai Tokkyo Koho 79 128 590 (Chem.
Abstr., 1980,92, 146 819).
358 He teroc y c Iic Chemistry
(315) (216)
an alternative cyclization gave only imidazo[ 1,5- b ] p y r i d a ~ i n e s . In
' ~ ~the ha!o-
genation of s-triazolo[4,3-h]triazepinones (216) it was possible to halogenate
the triazepirle ring selectively at C-7 or (and) the triazole ring at C-3 by selection
of the agent and reaction conditions."'
The 1,2,4-benzotriazepin-5-one(217) did not react with methyl iodide,
dimethyl sulphate, or diazomethane, but with methyl fluorosulphonate it gave
not the expected 1-methyl-derivative but the relatively stable quaternary salt
(218).This underwent ring-contraction to form (219) on treatment with acid.136
'34 R. Briickner, J.-P. Lavergne, and P. Viallefont, Liehigs A n n . Chern., 1979, 639.
'"
13h
E. M. Essassi, J.-P. Lavergne, and P. Viallefont, J. Heterocycl. Chem., 1979, 16, 1297
M. Bianchi, E. Hausermann, and S. Rossi, J. Heterocycl. Chem., 1979,16, 1411.
Eight-Membered and Larger Ring Systems
BY G . M. BROOKE
1 Eight-Membered Rings
One Heteroatom.-Ring-opening reactions have been used to prepare nitrogen-
containing compounds. Thus the fused p -methoxy-p-lactam (1) reacts with
HOAc, water, and EtOH to form the enamine ketone derivative (2),’ while (3)
and (4), which are intermediates in syntheses related to mitornycin anti-tumour
antibiotics, have been obtained by the photochemical oxygenation of (5)* and the
electrophilic ring-opening of (6) with trifluoroacetic anhydrideY3
respectively.
Q&+,; 2;$
H Mey7J-J
MeM\ e0
0 0 0
(1) (2) PhCH,
(3)
N
PU Dh
AcO ‘7
COCF,
(4)
Ring-expansion reactions have been carried out in a dienone-phenol rearrange-
ment of (7) to the oxygen-containing heterocycle (8) with 30% methanolic
sulphuric acid,4 and in a stereospecific synthesis of a 4-thiacyclo-octene via a
[2,3] sigmatropic shift’ (see last year’s Report, p. 412).
Two Heteroatoms.-1 ,4-Diazocine derivatives (9) in which R is H or an electron-
donating substituent, e.g. SiMe3, Me, or CONMe,, have ’H and I3C n.m.r. spectra
consistent with their being Huckel 1O n -electron delocalized planar systems,
whereas those with electron-attracting substituents, e.g. C02Me, S02Me, tosyl,
* Y. Hirai, S. Hirokami, M. Nagata, M. Morita, and T. Yamazaki, J. Org. Chem., 1980,45, 936.
T. Kametani, T. Ohsawa, and M. Ihara, Heterocycles, 1979, 12,913.
T. Kametani, K. Takahashi, M. Ihara, and K. Fukumoto, J. Chem. SOC.,Perkin Trans. I, 1979,1847.
M. Karhu, J. Chem. Soc., Perkin Trans. 1, 1979, 1661.
E. Vedejs and M. J. Mullins, J. Org. Chem., 1979,44,2947.
359
360 He terocy c1ic Chemistry
q (7)
0
-" (1
BMe0
YHCOBu'
(8)
N
R
P
(9)
\
Bu'
O
I
( 1 1) (12)
and COPh, behave like typical alkenes6 The related 6-acetoxy-l,4-dithiocin (10)
has spectral properties, reactivity, and an X-ray structure which indicate that it
is a non-planar molecule with no aromatic ~ h a r a c t e r . ~
The extremely unusual 1,5-oxazocine derivative (11) is formed from (12) by a
sequence of reactions involving hydrolysis of the formate ester with NaHCO,,
followed by ring-opening of the four-membered ring, a 1,4-dehydration reaction,
and finally rearrangement of the unstable intermediate on attempted isolation
by chromatography on silica.' Ozonolysis of 1,4-dihydronaphthalene in methanol
gives the expected peroxide.'
2 Nine- and Ten-Membered Heterocycles

Another reaction that is relevant to the mechanism of the formation of the
alkaloid erysodienone in vitro is the K,[Fe(CN)6]-induced para-para oxidative
coupling of the phenol (13) to the azoninone derivative (14)." Oxymercuration-
demercuration [by Hg(OAc);?and then NaBH,] of the cyclic lactam (15) resulted
in the regio- and stereo-specific transannular formation of (16).'* The conforma-
tion of (15) is represented by (17), in which there is no steric crowding by the
methyl group. The ring is believed t o be responsible for the course of the reaction.
Isomerization of the trans- pyridazino-azonine derivative (18) to the cis- isomer
in boiling benzene probably reflects a release of skeletal strain12 and contrasts
with the cis -+ trans isomerization found previously for the potassium salts of the
H. J. Altenbach, H. Stegelmeier, M. Wilhelm, B. Voss, J. Lex, and E . Vogel, Angew. Chem., Int.
Ed. Engl., 1979,18,926; M . Breuninger, B. Gallenkamp, K. H. Mueller, and P . Schoenholzer, ibid..
p, 964.
' H. J. Eggelte, F. Bickelhaupt, and B. 0. Loopstra, Tetrahedron, 1978, 34, 3631.
M. M. Campbell, D. I. Rawson, and A. Forbes Cameron, Tetrahedron Lett., 1979, 1257.
' 0. V. Topalova, Nauchn. Om. Pererab. Nefti Gaia Neftekhim., Tezisy Dokl., Vses. Konf,, 1977,
191 (Chem. Abstr., 1980, 92, 58 482).
l o A . G. M. Barrett, D. H. R. Barton, and D. A. Widdowson, J. Chem. SOC.,Perkin Trans. 1, 1979,662
" S. R. Wilson and R. A. Sawicki, J. Org. Chem., 1979,44, 330.
A. G. Anastassiou, M. Sabahi, and R. Badri, Tetrahedron Lett., 1978, 4755.
Eight-Membered and Larger Ring Systems 36 1
OH
Me0 \
MHe 0 O/ V ' 3
(13)
O I -/ OMe
l
Me0
@I
\
/
NH
OH
(14)
related benzannulated system. An optically active heptamethylene carbodi-

imide (19) has been synthesized by oxidation of the urea precursor with HgO
and chromatography of the product on partially acetylated cellulose. l 3 The
smaller nine-membered ring (20) was shown by variable-temperature 'H n.m.r.
to have a small free-energy barrier for interconversion of the spectroscopically
distinguishable a -methylene hydrogens; this may be caused by the configura-
tional instability of nitrogen and various conformational effects. l4
I
6
The condensation of (21) with methanal gave (22) as the isolated crystalline
product, i.e. a dimer of the expected compound (23).15However, 'H n.m.r.
showed that, in CHC13, dissociation of (22) to (23) does occur, but that, in
addition, the ion (24) is present in the equilibrium. The intermediate that is
believed to be responsible for these interconversions is (25).
(22)
13
0. Cervinka, V. Dudek, Z. Stihel, and J. Zikrnund, Collect. Czech. Chem. Commun., 1 9 7 9 , 4 4 2 8 4 3
(Chem. Abstr., 1980, 92, 128 879).
14
R. Damrauer, D . Soucy, P. Winkler, and S. Eby, J. Org. Chem., 1980,45,1315. See also R. R. Hiatt,
M.-J. Shaio, and F. Geoges, ibid., 1979, 44, 3265.
15
T. A. Crabb and G. C. Jackson, J. Chem. SOC.,Perkin Trans. 2, 1979, 504.
Bu'
(27)
An intriguing transannular brominolysis reaction with pyridinium hydro-
bromide perbromide has been proposed for the facile ring-opening reaction of
(26) to (27).16
3 Macrocycles
Systems containing Nitrogen as the only Heteroatom.-One Nitrogen Atom. The
azaC14lannulene (28) has been synthesized by the photolysis of (29) in pentane
at -7OoC.l7 Its aromatic character is demonstrated by the large difference in
chemical shifts of the three inner and the ten outer protons of ca 9.5 p.p.m.
Variable-temperature 'H n.m.r. moreover demonstrates that the ring is confor-
mationally mobile, producing an equilibrium of two degenerate species.
An improved one-step conversion of alicyclic ketones (30) into lactams (31;

n = 3-10) involves the use of hydroxylamine-0-sulphonic acid and methanoic
acid at reflux temperature.18 Treatment of 1-chloro- 1-nitroso- and 1-chloro- 1-
nitro-cycloalkanes (32) with Ph3P and then hydrolysis of the intermediate chloro-
imine provides a new route to (31; n = 3-6, or 10).19
The photochemical behaviour of the keto-azirine (33) depends on the
wavelength of the radiation.*' If A = 254 nm, in ether, the oxazolophane (34) is
formed, but if A > 300nm an unprecedented rearrangement to the keto-
ketenimine (35) occurs.
l6 M.-K. Au, T. C. W. Mak, and T.-L. Chan, J. Chem. SOC.,Perkin Trans. 1, 1979, 1475.
l7 H. Roetteie and G. Schroeder, Angew. Chem., Znt. Ed. Engl., 1980, 19, 207.
G. A. Olah and A. P. Fung, Synthesis, 1979, 537.
l 9 I. Sakai, N. Kawabe, and M. Ohno, Bull. Chem. SOC.Jpn., 1979,52,3381.
2o S. Albanesi, A. Marchesini, and B. Gioia, Tetrahedron Lett., 1979, 1875.
Eight-Membered and Larger Ring Systems 363
Four Nitrogen Atoms. Compound (36), a water-soluble material that has nitrogen
atoms which bear long alkyl chains, has been synthesized as a potential model of
an enzyme that is capable of incorporating a hydrophobic substrate by guest-host
interaction.21The inhibition of the rate of alkaline hydrolysis of p-nitrophenyl
3,5-dimethylcyclohexylacetateby a factor of 147 relative to the spontaneous rate
in the absence of (36) suggests that the ester carbonyl group of the substrate is
*;*
indeed effectively shielded from attack by external HO- ions, as a result of the
guest molecule, as a whole, being buried and held by hydrophobic and electro-
static forces in a proposed 'octopus-like' structural complex.
RN
moq)JN
0
(36) R =
\ /
(CH2)loC02H
The simple substrates benzylideneacetone and H2N(CH2)2NH2 react together
to form a complex equilibrium mixture that is centred on the initial condensate
P hCH=CHC(Me) =N(CH2)2NH2.22 Isomeric transoid macrocycles (37) are
formed, together with the double condensate [PhCH=CHC(Me)=NCH2I2
and the seven-membered heterocycle (38). The oxazapentadienium salts (39)
condense with H2N(CH2)2NH2to provide a useful route to other fourteen-
membered -ring compounds.23
The cyclic tetramine fNH(CH2)3NH(CH2)2]2 gives a mixture of products when

it reacts with P(NMe2)3,in which the phosphorane tautomer (40) predominates,
in contrast to the PI1' tautomers which arise from the isomer
tNH(CH2>3[NH(CH2)212NH(CH,),).24
21 Y. Murakami, A. Nakano, R. Miyata, and Y. Matsuda, J. Chem. Soc., Perkin Trans. 1, 1979, 1669.
22 0. H. Hankovsky, K. Hideg, D. Lloyd, and H. McNab, J. Chem. SOC.,Perkin Trans. 1, 1979, 1345.
23 D. Lloyd, H. McNab, and D. R. Marshall, J. Chem. SOC.,Perkin Trans. 1, 1978, 1453.
24 T. J. Atkins and J. E. Richman, Tetrahedron Lett., 1978, 5149.
364 Heterocyclic Chem istry
Systems containing Nitrogen and Other Heteroatoms. Both kinetic and thermo-
dynamic data show that, of the series of nickel(I1) complexes of related 0 2 N 2 -
donor macrocycles in the fourteen- to seventeen-membered range, the sixteen-
membered compound (41) is the most stable.2s*2h The macrocycle (42) shows
strong ligand binding with Ca2t.27
Vacuum pyrolysis of (43) effected extrusion of SO, and loss of chlorine, with
the formation of (44).28
q n
o
NH HN
0
9 Ho+ r o T N - O H
bd
I
I (42)
(41)
Systems containing Heteroatoms other than Nitrogen. Over the past year, a number
of important syntheses of macrocyclic esters have been reported. A decarboxyla-
tive double fragmentation process that is shown, in principle, in Scheme 1 has
been exploited in the synthesis of (45) by heating the amidinium salt (46) at its
melting point (180 "C) for 3 minutes.29 The process offers the possibility of
varying the position of the C=C bonds in the macrolide by changing the site of
both the tosylate and carboxylate groups.3"
In order to overcome unfavourable entropy effects which lead to the formation
of polyethers from o -hydroxy-carboxylic acids, rather than lactonization, a rapid
intramolecular esterification process, under mild conditions, has been developed
/
0
0 \ / 1 / 'o \
II
r / c \n,c
\ /
\7
\
C(
, ; .-.c f - i'x + co,+ //c + \c,+ (7c
' + x-
- 0 C O I C
/ \ It / \
/c\ 0
Scheme 1
25 A. Ekstrom, L. F. Lindoy, and R. J. Smith, J. A m . Chem. Soc., 1979,101,4014.
26 K. R. Adam, L. F. Lindoy, R. J. Smith, G. Anderegg, K . Henrick, M. McPartlin, and P. A. Tasker,
J. Chem. SOC.,Chem. Commun., 1979,812.
27 E. Amble and J. Dale, Acra Chem. Scand., Ser. B, 1979, 33, 698.
28 H. J. J. B. Martel, S. McMahon, and M. Rasmussen, Aust. J. Chem., 1979, 32, 1241.
29
D. Sternbach, M. Shibuya, F. Jaisli, M. Bonetti, and A. Eschenmoser, Angew. Chem., Int. Ed. Engl.,
1979, 18, 634.
") M. Shibuya, F. Jaisli, and A. Eschenmoser, Angew. Chem., Int. Ed. Engl., 1979, 18, 636.
I
Me
(45)
by forming the mixed anhydride from the carboxylic acid moiety with 2,4,6-
trichlorobenzoyl chloride in the presence of Et3N, followed by lactonization in
boiling benzene in the presence of 4-dimethylarnin0pyridine.~~ The process has
permitted the cyclization of (47),which contains sensitive functional groups that,
under less mild conditions, lead to a non-lactonized product. Forcing together
the proximity of terminal functionalities of acyclic systems is expected to increase
the efficiency of the ring-closure reaction dramatically. Thus the
transesterification process with (48), in which dipole attraction brings the
alkoxide oxygen close to the complexed cation, gives 44% of the twelve-
membered lactone, compared with only 1o/' by using CH3CH2SCO(CHJ1,0- K'
. ~ ~ advantages of the template effect of a crown
under the same c o n d i t i o n ~The
ether, however, diminish at very high dilution. An efficient double inter-
6 COK0i2
molecular alkyl-oxygen ester-forming reaction takes place between (49) and (50)
HO ic'
I- CO,H
(47) L o 0)
U
(48)
0 K+
(49) (50)
in DMF, to yield a heterocycle that contains a thirty-two-membered ring; the
structure of this heterocycle is closely related to those of the nactin antibiotic^.^^
A simple, efficient synthesis of macrocyclic lactones and/or diolides also occurs
when the caesium salts of w - bromo- or w -iodo-carboxylic acids, Br(CH2),C0,
Cs' ( n = 8-15), are heated in DMF at 40°C.34 High-dilution techniques are
31
J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, andM. Yamaguchi, Bull. Chem. SOC.
Jpn., 1979,52,1989.
32 W. H. Rastetter and D. P. Phillion, Tetrahedron Lett., 1979, 1469.
33
A. Samat, J. Elguero, and J. Metzger, J. Chem. SOC., Chem. Commun., 1979, 1182.
34
W. H. Kruizinga and R. M. Kellogg, J. Chem. Soc., Chem. Commun., 1979, 286.
not necessary, yet a template effect was not anticipated. The optically active
compound (51) [the ( + )-(lR, 5R)-enantiomer] underwent cationic poly-
merization with BF,.Et20 in CHCl, at -40°C to give the cyclic hexamer (52)
e x c l ~ s i v e l y in
, ~ contrast
~ to the oligomerization of the rucernic monomer under
the same conditions, which gave only the cyclic tetramer. It was considered that
the unusually high selectivity for the formation of (52) suggests that there is a
growing chain, consisting of configurationally identical monomeric units, which
tends to take a conformation that is especially favourable for ring-closure to the
cyclic hexamer. Moreover, the formation of the tetramer from the rucemic
monomer indicates that this oligomer is an optically inactive compound, consist-
ing of alternating enantiomeric units. A new method for forming medium-sized
and large lactones is based on the intramolecular displacement of the w - halogen,
X, by an a-carbanion that is generated next to the sulphur in ( 5 3 ) , using the
qo 0
4
c-0
PhS X
potassium salt of hexamethyldisilazane in THF.36An intramolecular Wittig-type

reaction with compounds that contain the keto-phosphonate group
-COCH2PO(OR)2 at one end of an internal ester chain and an aldehyde group
at the other end is a useful method for the construction of macrocyclic lactones
with an a@-unsaturated carbonyl group.,'
The annulenone (54), expected to be planar and strain-free, has been synthe-
sized. The resonance of the ring protons in the 'H n.m.r. spectrum indicates that
it is a dioxido[16]annulene Moreover, the peak arising from the
keto-carbonyl group (1700 cm-') in the i.r. spectrum is very close to the corre-
sponding value of cyclcpentadienones but differs considerably from that of
[ 15lannulenone dioxide (1645 cm-'), so the carbonyl group belongs electroni-
cally to the five-membered-ring moiety rather than to the fifteen-membered ring.
35 M. Okada, H. Sumitomo, and I. Tajima, J. Am. Chem. Soc., 1979,101,4013.
36 T. Takahashi, K. Kasuga, and J. Tsuji, Tetrahedron Lett., 1978, 4917.
37 K. C. Nicolaou, S. P. Seitz, M. R. Pavia, and N. A. Petasis, .I. Chem., 1979,44, 4011; G. Stork
Org.
and E. Nakemura, ibid., p. 4010.
38 H. Ogawa and A. Chisaka, Tetrahedron Lett., 1978,4811.
Cyclic polysulphur compounds containing two, three, and four sulphur atoms
in the bridges have been obtained, in low yields, from the aromatic compounds
1,3-(Me0)2C6H4(in CHC13)39and mesitylene (in Et20)40with S2C12and an iron
catalyst, in very dilute solutions. The fourteen-membered ring containing ten
sulphur atoms, (S5COCO)2,is formed from [(C5H5)2TiS5] and CICOCOC1.41
The complex formed between +S-CH2CH2CH2j4 and Hg"(C104)2is the most
stable complex yet known that involves Hg" and a macrocyclic t h i ~ e t h e rThe
.~~
X-ray structure indicates the presence of very little strain, yet even more stable
complexes (by a factor of 10) are formed with the open-chain compound
(MeSCH2CH2SCH2)2CH2, so that previous explanations of the 'macrocyclic
effect' are inadequate when applied to Hg".
Crown Ethers and Related Compounds.-Synthesis. The caesium salts of various
diphenolic compounds can be prepared with ease from Cs2C0, in MeOH, and
they react with BrCH2(CH20CH2),CH2Brto give crown The most
sensitive compound examined, i.e. 2,3-dihydroxypyridine, gave di-0-alkylated
materials ( n = 3 , 4 , or 5), in contrast to methylation (with MeI), which gave the
N-methyl-3-methoxy-compound. Catechol and substituted catechols (having an
ortho CHO, COMe, C 0 2 E t , or C H 2 0 H group) and poly(ethy1ene glycol) di-
tosylates react to form good yields of crown ethers in MeCN in the presence of
alkali-metal The fluoride ion acts as a strong base, but the cations
also act as a template, though the effectiveness of CsF and RbF being greater
than that of KF, even for benzo-15-crown-5 and benzo-18-crown-6, is in contrast
to the accepted picture of the template cation fitting into the cavity of the crown
ether that is formed.
Crown ethers with fluctuating ring size (a supply of activation energy E , <
20 kcal mol-' suffices to vary the ring size reversibly), which have been called
'breathing crown ethers', have been synthesized which incorporate bullvalene
into the ring.45 For bullvalene with two equal substituents, twelve positional
isomers, i.e. four each of the 1,2-, 1,3-, and 1,4-isorners, can be formulated, so
that for (55; n = 1) and (55; n = 2) the ring size varies between eleven and
thirteen members, and between twenty and twenty-two members, respectively.
The bridged 1,5-naphtho-22-crown-6-ether (56) requires an energy of activa-
tion, E,, of ca 6.3 kcal mol-' to convert it into its enantiomer (57) by a 'rope-
skipping' process.46The smaller 19-crown-5 compound interconverts less easily
( E , = 21 kcal mol-I). Generation of the binucleophiles R(Z)C=C(Z)R (Z =
0 or NPh) from RC(=Z)C(=Z)R, by electrolysis in DMF that contains
BuiN' I-, in the presence of TsOCH2(CH20CH2),CH20Ts(n = 1-3) gives the
corresponding macrocyclic A wide variety of polyethers and
39 F. Bottino, S. Foti, and S . Pappalardo, J. Chem. SOC.,Perkin Trans. 1, 1979, 1712.
40 F. Bottino, S. Foti, S. Pappalardo, and N. Bresciani-Pahor, Tetrahedron Lett., 1979, 1171.
41 H. W. Roesky, H. Zamankhan, J. W. Bats, and H. Fuess, A n g e w . Chem., Int. Ed. Engl., 1980,19,
125.
42 T. E. Jones, L. S. W. L. Sokol, D. B. Rorabacher, and M. D. Glick, J. Chem. Soc., Chem. Commun.,
1979, 140.
43 B. J. VanKeulen, R. M. Kellogg, and 0. Piepers, J. Chem. Soc., Chem. Commun., 1979, 285.
44 D. N. Reinhoudt, F. DeJong, and H. P. M. Tomasson, Tetrahedron Lett., 1979, 2067.
45 G . Schroeder and W. Witt, Angew. Chem., Int. Ed. Engl., 1979,18,311.
46 H. S. Brown, C . P. Muenchausen, and L. R. Sousa, J. Org. Chem., 1980,45, 1682.
47 K. Boujlel and J. Simonet, Tetrahedron Lett., 1979, 1497.
related compounds have been synthesized which incorporate other functional

groups in the ring (e.g. a l k ~ n e 4, ,~6~- ~ y r i m i d i n o ,m
~ ~ n o e s t e r , ~and
" diester
containing a furan'' and a pyridine52subcyclic unit), and some pharmacologically
active substituents have been appended to crown ether^.'^
Efects of Crown Ethers on Chemical Reactions. Nucleophilic aliphatic substitu-
tion reactions in the presence of crown ethers have been studied with respect
both to their kinetics and the nature of the products. As a phase-transfer catalyst,
dicyclohexyl-18-crown-6 polyether has only a small effect on the reactivity range
of a number of anions, effecting the displacement of MeS03- from n-
C,H,,0S02Me in both PhCI-H20 mixtures and in PhCl alone. The sequence of
activities in both cases is N3 > I = Br > CN- > C1- > SCN-, and it was
concluded that the crown ether was not producing naked anions.54The compound
( 5 8 ) ,immobilized on the polymer silochrome S-120, is an effective phase-transfer
catalyst for the formation of esters from KOAc and RBr (R = Bun or PhCH2)."
The relative rates of reaction through the two reactive centres of ambident
nucleophiles (NO2-, CN-, NCO-, and NCS-) with MeOSOzMe in different
solvents containing 18-crown-6 polyether have been examined,56while 0- versus
(58)
JX
S. A . Vartanyan, T. R. Akopyan, and E. G. Paronikyan, Arm. Khirn. Zh., 1979, 32, 471 (Chern.
Abstr., 1980, 92, 58 754).
4')
G. R . Newkome, A . Nayak, M. G. Sorci. and W. H. Benton, J. Org Chern., 1979,44, 3812.
511
K . Matsushima, N. Kawamura, and M. Okahara, Tetrahedron Let!., 1979, 3445.
51
J. S. Bradshaw, S. L. Baxter, D. C. Scott, J . D. Lamb, R. M. Izatt, and J . J. Christensen, Tetrahedron
Lett., 1979, 3383.
52
J . S. Bradshaw, G . E. Maas, J. D. Lamb, R. M. Izatt, a n d J. J. Christensen, J. A m . Chern. SOC.,1980,
102,467.
53
U. Elben, H. B. Fuchs, K. Frensch, a n d F. Voegtle, Liebigs A n n . Chem., 1979, 162 (Chem. Abstr.,
1979,91, 193 283).
s4
D. Landini, A. Maia, F. Montanari, a n d F. M. Pirisi, J. Chern. SOC.,Perkin Trans. 2, 1980, 46.
55
A. V. Bogatskii, N. G. Luk'yanenko, a n d V. N. Pastushok, Dokl. Aknd. Nauk SSSR, 1979, 247,
1153 (Chern. Abstr., 1980, 92, 6206).
56
H. Lemmetyinen, L. Lehtinen, and J. Koskikallio, Finn. Chern. Lett., 1979, 72 (Chem. Abstr., 1980,
92, S901).
C-allylation of PhO- Na' with H,C=CHCH,Cl in a variety of solvents in the
presence of different crown ethers is most effective in each case when using
poly(vinylbenzo-15-crown-5)polyether.57Only in the presence of the crown
ethers 15-crown-5 and 18-crown-6 are the anions in potassium phthalimide and
sodium saccharinate, respectively, sufficiently activated to bring about
nucleophilic aromatic substitution of the 4-fluorine in pentaflu~ropyridine.~~ The
formation of 2,4-dinitrophenol, in addition to the expected ether, from 2,4-
dinitrochlorobenzene and potassium 2-propoxide in 2-propanol-benzene ( 1 : l ) ,
in the presence of dicyclohexyl-18-crown-6 polyether, has been accounted for
on the basis of a nucleophile-radical reaction (S,J).~~
The double elimination of HHal from 1 , l - and 1,2-dihalogeno-alkanes to
give alkynes (terminal and internal) under very mild conditions is preparatively
very simple in petroleum ether, using solid KOBu' and catalytic amounts of
18-crown-6 polyether.60 Different transition-state structures within the E 2
mechanism, as well as different initial-state solvation conditions, have been
proposed to rationalize the effects of equimolar amounts of crown ether and base
on the dehydrochlorination of (p-ClC6H4)2CH2CH~3-,,Clx ( x = 1, 2, or 3).61
15-Crown-5 and 18-crown-6 polyethers caused decreases in the rate constants of
the dehydrochlorination with EtO-, but increases with Bu'O- (by factors of
16-91, respectively). The orientation in 1,2-eliminations from 2-iodobutane
that are caused by a variety of nitrogen and carbon bases in DMSO, with the
counter-ion of the base being varied from Na' to K', and then to K' in the
presence of 18-crown-6, has revealed that ion pairing is important with
the stronger anilide bases that were examined (e.g. that from rn -chloroaniline)
and especially with the sodium salts from Me2S02and MeS02Ph.62In each case,
the relative proportion of terminal alkene is smaller than when the base is
freely dissociated.
The cavity of crown ethers is not involved in the interaction with Br2; rather,
a bromine-oxygen interaction is at issue. A mixture of dibenzo-18-crown-6 and
bromine, when used as a bromine-addition reagent, is completely selective
(giving trans-addition) for (E)-PhCH=CHMe in a variety of solvents, regardless
of solvent polarity, in contrast to the use of bromine alone or of bromine plus
. ~ ~implication of this observation is that the bromonium ion (59) is
~ y r i d i n eThe
stabilized by the crown ether relative to the open carbo-cation in all solvents,
and moreover this stabilization is greater than that found in the ion from the
(2)-isomer, which nevertheless exhibits enhanced stereoselective addition. The
57
S. Akabori, S. Mujarnoto, and H. Tanabe, J. Polym. Sci., Polym. Chem. Ed., 1979, 17, 3933 (Chem.
Abstr., 1980, 92, 128 506).
W. Rasshofer and F. Vogtle, Tetrahedron Lett., 1979, 1217.
59
C. Mariani, G. Modena, G. P. Pizzo, G. Scorrano, and L. Kistenbruegger, J. Chem. Soc., Perkin
Trans 2, 1979, 1187.
" E. V. Dehmlow and M. Lissee, Liebigs A n n . Chem., 1980, 113 (Chem. Abstr., 1980,92, 197 852).
'' A. Jarczewski, G. Schroeder, and K. T. Leffek, J. Chem. SOC.,Perkin Trans. 2, 1979, 866.
R. A. Bartsch, D. K. Roberts, and B. R. Cho, J. Org. Chem., 1979,44,4105.
63
K. H. Pannell and A. Mayr, J. Chern. SOC.,Chem. Commun., 1979, 132.
addition of 12-crown-4 polyether to the solutions used during the preparation of
nickel boride increases its activity (by a factor of ca 1.5) as a catalyst for the
hydrogenation of cyclohexene, and cyclo-octene, while its addition to pre-formed
catalyst results in deactivation of its catalytic activity (by a factor of ca 0.75).64
No method was found which changed the selectivity of the catalyst. The selective
reduction of the C=C bond in PhCH=CHCOMe is accomplished readily and
in high yield in a two-phase benzene-water system by means of a mixture of
Fe(C0)5,primary amine RNH2, and the crown ether dicyclohexyl-18-crown-6.65
The effective reducing agent is [HFe(CO),]-, which arises from Fe(CO), and the
HO- that is liberfted into the organic phase as a result of the partitioning of the
[crown ether-RNH,] HO- complex from the aqueous phase. The Wittig re-
arrangement of the fluorenyl ether (60) is readily effected with solid K O H in
benzene, using 8-crown-6 polyether as a phase-transfer agent.66
An extensive kinetic study of the decomposition of p-(t-buty1)benzene-

diazonium tetrafluoroborate when complexed with forty different macro-
cyclic multidentate compounds in 1,2-dichloroethane has enabled the influence
of some structural parameters upon the complexation efficiency of the ligand to
be as~essed.~'Stronger complexation was found with the 21 -membered-ring
macrocycles than with the corresponding 18- or 24-membered-ring compounds;
electron-releasing substituents on any aromatic rings in the macrocycle promoted
stronger complexation; the replacement of an oxygen atom of the crown ether
by a pyridyl nitrogen enhanced association, but substitution by an oxygen in an
ester group or by a sulphur atom diminished complexation. An ESCA study of
the complexes of ~ - B u ~ C ~ H and ~ Nof~PhNH3'I
~ B F ~ with
~ dibenzo-18-crown-6
~
has been carried out, and the data are consistent with the geometries previously
postulated for these species.68 The zwitterion (61), which forms a 1: 1 complex
with 18-crown-6 polyether in the solid state, is presumed to be tightly associated
in solution in PhCN, since loss of nitrogen to give (62) is retarded by a factor of
0.8 relative to the reaction that occurs without the macrocycle Further
(61) (62)
64
M. Kajitani, J. Hasegawa, E. Kasai, and A. Sugimori, Tetrahedron Lett., 1979, 2407.
F. Wada, R. Ishihara, Y. Kamohara, and T. Matsuda, Bull. Chem. SOC.Jpn., 1979,52, 2959.
66
Y. Yamamoto, J. Oda, and Y. Inouye, Tetrahedron Lett., 1979, 2411.
'' R. A. Bartsch and P. N. Juri, J. Org. Chem., 1980,45, 1011.
68 0. Bohman, P. Ahlberg, R. Nyholm, N. Martensson, K. Siegbahn, and R. A . Bartsch, J. Chem.
Res.(S), 1979, 292.
" W. A. Sheppard, G. W. Gokel, 0. W. Webster, K. Betterton, and J. W. Timberlake, J. Org. Chem.,
1979,44, 1717.
Eight-Membered and Larger Ring Systems 37 1
work on the decarboxylation of potassium 6-nitrobenzisoxazole-3-carboxylate
in benzene, which is strongly catalysed by crown ethers and their polymers, has
been carried Using poly(4-vinylbenzo-18-crown-6),the rate of decarboxy-
lation increases by a factor of 7 over that for the monomeric analogue
4-methylbenzo-18-crown-6; this has been attributed to the probable enlarge-
ment in the inter-ionic distance of the crown-complexed ion pair.
Reactions of the Macrocyclic Rings of Crown Ethers and Related Compounds.
Further attempted syntheses that were designed to incorporate a 1,4-dihydro-
pyridine unit into a macrocyclic ring, so that it is capable of mimicking biological
hydrogen-transfer agents, have been (the first success being noted
in last year's Report). The first synthesis of an amino-acid-containing crown ether
(63) has been Not only was the molecule chiral, but it also contained
the 1,4-dihydropyridine ring system, which, with equimolar amounts of

PhCOCF3 and Mg(C10&. 1.5H20,in MeCN, at 5 5 "C, over 5 days, gave optically
active PhCH(OHjCF3, i.e. the product of asymmetric reduction, with an optical
yield of 68%, the (Sj-enantiomer being in excess. In this reaction the encapsu-
lated metal ion in [(1,4-DHP)Mg2'] crown complexes with the carbonyl com-
pound, forming a ternary complex in which the carbonyl group is activated toward
hydride acceptance through its complexation to MgzC.
Cram has allowed large excesses of :he cyclic and acyclic thiols R'SH [(64) and
( 6 5 ) respectively] to react with the p-nitrobenzoate ester salts of enantiomeric
~ c ~ o ? o
' ' 0 \
(64) X = CHZCHZ
(65) X = -Me Me-
'' J . Smid, A. J. Val-ma, and S. C. Shah, J. Am. Chem. SOC.,1979, 101,5764.

7' G. R. Newcombe and T. Kawato, J. Org. Chem., 1979, 44,2693.
72 G. R. Newcombe, T. Kawato, a n d A. Nayak, J. Org. Chem., 1979,442697.
73 J . G. DeVries and R. M. Kellogg, J. A m . Chem. Soc.. 1979. 101, 2759.
R'S- + R'CH-CO, NO, --* R'SCOCHR' + O2N

+I +I
"3 NH,
Scheme 2
amino-acids and has measured the pseudo-first-order rate-constants for the

reaction, which proceeds as shown in Scheme 2.74
The extreme values of kcyc,e/k,,on.cyc,e
derived from (S)-(64)and (S)-(65)varied
from >130 to >1170 for reaction with the L-ester salts of alanine and leucine
respectively, demonstrating stabilization of a transition state by complexation
with the macrocycle. Massive concentrations of K' acted as a competitive and
dominant binder of (64),and eliminated the acceleration caused by the structured
complexation. The preference of (S)-(64)over its enantiomer (R)-(64)to react
with the L-amino-ester salts and the relative values of these chiral recognition
factors has been rationalized o n the basis of the more stable (S)-(64) to
L-coAiguration for complexation in the rate-limiting transition state (66). Com-
parisons were made between these reactions and those catalysed by enzymes.
Formation of Host-Guest Complexes. The host (67), containing bis-dinaphthyl

units, which was discussed in last year's Report as being a highly discriminating
host, has been attached to cross-linked polystyrene through the unit
CH2CH20CH2at the remote position 6.75Columns of this material can be used
for the chromatographic resolution of the enantiomers of amino-acid and methyl
ester salts, using CHCl, plus MeCN as solvent. Experiments confirmed the
predictions that the enantiomer that is more strongly complexed to the (R,R)-host
is the D-enantiomer, in which stereoelectronic features between host and guest
are more complementary, as shown in (68). A novel catalytic resolving machine
has also been devised in which one enantiomer of the water-soluble chiral
74 Y . Chao, G. R. Weisman, G . D. Y. Sogah, and D. J. Cram, J. Am. Chem. SOC.,1979,101, 4948.

'' G. D. Y. Sogah and D. J. Cram, J. Am. Chern. Soc., 1979, 101. 3035.
(68)
quaternary ammonium salt is selectively transported through chloroform that
contains an optically pure host; this mimicks (in some way) the biological
transport of amino-acids and their derivatives through lipophilic cells walls.76 A
W-tube was constructed, into the left-hand U-tube of which was placed a solution
of the (SS)-enantiomer of host (67) in chloroform, and into the right-hand U-tube
was placyd a solution of the (RR)-host (67). The racemic guest PhEH-
(C02Me)NH, Cl-. was placed in the central arm, simultaneously contacting the
separate pools of solutions in chloroform; over a period of ca 24 hours, the L-
and D-enantiomers of the guest were preferentially delivered to aqueous sol-
utions lying in the left- and right-hand arms of the W-tube respectively, uia
selective complexation of these guests with their complementary hosts. The
optical purities of the enantiomers ranged from 70 to 90%, depending on the
experimental details.
Many new macrocycles have been synthesized with the objective of identifying
the varieties of complementary host-guest relationships in complexation. Com-
pound (69) is ranked as one of the best general ligand systems towards the
alkali-metal cations and NH4+,and it showed high selectivity for ions.77It formed
a particularly strong bond with Na’, and molecular models show that the two
P+O groups fall on an axis which is at right-angles to the best plane of the
macro-ring and which passes through its centre, creating a roughly spherical hole
that is lined with thirty-two electrons, associated with eight oxygen atoms. The
‘jaws-like’ host (70) did not come up to the expectations based on molecular
models with regard to the strength of its complexation with C S + ,though
~~ (71),
0
0
-
(69) R = CH,P(O)(OEt),
(70)
76 M. Newcomb, J . L. Toner, R. C. Helgeson, and D. J. Cram, J. A m . C h m . Soc., 1979, 101, 4941.

77 R. C. Helgeson, G. R. Weisman, J. L. Toner, T. L. Tarnowski, Y . Chao, J. M. Mayer, and D.J.
Cram, J. A m . Chem. SOC.,1979, 101, 4928.
374 He terocyc 1ic Chemistry
(72) n = 2
with a different 'hinge' in its 'jaws-like' structure, provides almost the best ligand
that has yet been examined for binding Cs' in a sandwich-type structure;78 a
maximum of ten oxygen-to-metal-ion contacts can be made to the host at any
one time. The doubly bridged host (72) is a powerful and selective ligand,
especially towards K'.78 A wide variety of macrocyclic polyethers have been
prepared which contain methoxy-aryl groups.79The m -teranisyl compound (73)
and compound (69) are currently the best and most differentiating hosts that have
been examined by Cram and co-workers; those studied also include macro-
cycles containing phosphoryl (P=O), urea (N2C=0), pyridine, pyridine oxide
(N-FO),'~)and negatively charged acetylacetonide units.'l In the last case,
collecting and organizing these p -ketonide ligands in appropriately sized and
shaped macro-rings can vary the binding power of these ligands to various metal
ions by factors of up to lo6 in the values of the formation constants. It has been
observed that compound (74) forms far stronger bonds with the physiologically
important ions Cu2+,Co2+,Zn2', Ca2', and Mg2' than with Na'.
A macrocycle that bears anionic groups has been prepared which forms by far
the most stable guanidinium and ammonium (NH,') complexes8* that are cur-
rently known in aqueous solution. The guanidinium ion complex (75) is the more
Me
Me
(73)
'* R. C. Helgeson, T . L. Tarnowski, and D. J. Cram, J. Org. Chem., 1979, 44,2538.
'' K. E. Koenig, G. M. Lein, P. Stuckler, T. Kaneda, and D. J. Cram, J. Am. Chem. SOC.,1979, 101,
3553. See also D. J. Cram, T. Kaneda, G . M. Lein, and R. C. Helgeson, J. Chem. SOC., Chem.
Commun., 1979,948.
L. J. Kaplan, G. R. Weisman, and D. J. Cram, J. Org. Chem., 1979,44, 2226.
A. H. Alberts and D. J. Cram, J. A m . Chem. SOC.,1979,101, 3545.
'' J. M. Lehn, P. Vierling, and R. C. Hayward, J. C h m . SOC.,Chem. Commun., 1979, 296.
Eight-Membered a n d Larger Ring Systems 375
stable, however, as a result of geometrical factors permitting six strong hydrogen-
bonding interactions. Another biologically important heterocyclic ring system,
the imidazolium ion, also forms a complex through two favourable hydrogen-
bonding interactions, though as a consequence it is less strongly complexed.
R R
(75) R = COz-H&(CH2CH20H)3
A series of papers concerned with the formation of complexes between
aza-derivatives of crown ethers and primary alkylammonium salts have been
published by Sutherland, who has used the lineshapes of signals in variable-
temperature 'H n.m.r. experiments to analyse various types of guest-exchange
processes and conformational changes of the host molecules. Complexes of the
monoaza-15-crown-5 ether (76; n = 2) with (primary alky1)ammonium
thiocyanates R'NH3+ NCS- involve only a single face of the host macrocycle,
and the subsitituent R2 on the host and the alkyl group R ' on the guest are
syn- related in the complex.83 However, both diastereoisomeric complexes are
formed with the monoaza-18-crown-6 ether derivatives3 (76; n = 3). Host
molecules [77; X = (CH,), or (CH&], bearing two aza-crown ether rings, form
1: 1 sandwich complexes (78) with the bis(a1kylammonium) salt (79).s4 The
diaza-derivatives of crown ethers and (81)s6form only a single type of
complex, of similar stability, which is believed to have the all-syn structure, with
R'NH3+ NCS-, e.g. (82). Diaza-analogues of 18-crown-6 have been prepared,
and they form strong complexes with R'NH3+ NCS-.87 The complex from the
dibenzo-compound (83) appears to exist in only one form, in which the guest lies
n ono
(76)
e,, ,,2c, .s
L.J
N-X-N
(77)
LJ
83 M. R. Johnson, I. 0. Sutherland, and R. F. Newton, J. Chem. SOC.,Perkin Trans. 1, 1979, 357.

84 M. R. Johnson, I. 0. Sutherland, and R. F. Newton, J. Chem. SOC.,Chem. Commun., 1979, 306.
85 S. J. Leigh and I. 0. Sutherland, J. Chem. SOC.,Perkin Trans. 1, 1979, 1089.
86 L. C . Hodgkinson and I. 0. Sutherland, J. Chern. Soc., Perkin Trans. 1, 1979, 1908.
" L. C. Hodgkinson, M. R. Johnson, S. J . Leigh, N. Spencer, I. 0. Sutherland, and R. F. Newton, J.
Chem. SOC.,Perkin Trans. 1, 1979, 2193.
""'
NH3
2NCS
(79)
Me
(85) X=-CH2
uCH2-
(84) X = -(CH2)20(CH2)2- I
Ph
(86) R' = H , R2 = OMe
(89) R' = OMe,R' = H
on one face in an anti-relationship to the two N-methyl groups on the ring, but
other analogues (without, or with only one, fused benzo-ring) form equilibrium
mixtures of two or more different types of complex. The first examples of the
formation of 2 : 1 organic guest cation to host complexes have been reported,
between PhCH2NH3+ NCS- and (84)or (8S).88Two methods, using n.m.r.
spectroscopy, have been described for the measurement of chiral selectivity in
the formation of complexes between some chiral macrocyclic diamines and chiral
guest (primary a1kyl)ammonium salts in a single-phase ~ y s t e m , 'as
~ an alternative
procedure to Cram's, which relies on the distribution of a racemic guest
ammonium salt between an aqueous phase and an organic phase that contains
the chiral host molecule.
Chiral crown ethers have been constructed around carbohydrates as sources
of chirality. Variable-temperature 'H n.m.r. spectroscopy has shown that the 1 : 1
complexes of PhCH2NH3' NCS- and the crowns (86) and (87) can be interpreted
M. J . Bovill, D. J. Chadwick, M. R. Johnson, N. F. Jones, I. 0. Sutherland, and R. F. Newton, J.
Chem. SOC.,Chem. Commun., 1979, 1065.
x9 D. P. J. Pearson, S. J. Leigh, and I. 0. Sutherland, J. C h ~ mSOC.,
. Perkin Trany. 1, 1979, 31 13.
SCN
Ph
G (87) R' = H , R 2 = OMe
(88) 'Me (90) R' = OMe,R2 = El
in terms of equilibria involving both diastereoisomeric complexes (on the a - and
@-faces)of similar strength in the case of the galacto-crown (86),and preferential
(67%, at equilibrium at -75 "C) complexation at the @-faceof the gluco-crown
(87) as a result of a dipole-induced-dipole attraction between the 1,3-dioxan ring
in (87) and the phenyl group in the cation, as shown in (88).90In both hosts (86)
and (87), the oxygen of the a-m7thoxy-group at C-1 is believed to be involved
in the primary binding of the -NH3 centre to the a-face in addition to the six
crown oxygens, and the pyranoside oxygen at C-4 in the p-complex of (86) also
participates in the complexation. Unexpectedly, the anomeric galacto- crown (89)
formed the major complex (78%, at -90 "C) with the a -face, as did the anomeric
gluco-crown Consequently the authors proposed the existence of a
stabilizing secondary anomeric effect in the a -complexes which involves the
dipole associated with the anomeric region of @ -glycosides and an induced dipole
in the phenyl ring of PhCH2NH3+guests, as is illustrated with (90) in Scheme 3.
Scheme 3
Alteration of the stereochemistry of 2,3-fusion of the ring in (87) and the effect
this has on the ease of complexation with (primary alky1)arnmonium thiocyanates
. ~ ~ manno -derivatives (H-2a,H-3a) and the altro-
has been i n ~ e s t i g a t e d The
derivative (H-2a,H-3@)have association constants (K,) with Bu'NH3' NCS- in
CDC13 of 39 000 and <50 1 mol-', respectively, the latter (very low) value being
a consequence of at least one anti 0-C-CO unit within the molecule.* The 'H
* It is interesting to compare these values with the corresponding values of other crown ethers:
18-crown-6 (3 x 10'); compound (86) (201 000); compound (87) (2000); compound (89) (5800);
compound (90) (1300 1 mol-I).
90
D. A. Laidler and J. F. Stoddart, J. Chem. SOC.,Chem. Commun., 1977, 481.
'' R. B. Pettman and J. F. Stoddart, Tetrahedron Lett., 1979, 457.
92 R. B. Pettman and J . F. Stoddart, Tetrahedron Lett., 1979, 461.
n.m.r. spectrum of the manno-derivative indicated that the oxygen of the

pyranosidic ring participates in complex formation,? along with the other six
oxygens, and with PhCH2NH3' NCS- the major complex (74% at -75°C) is
associated with the p -face; a stabilizing dipole-induced-dipole interaction has
again been used to rationalize the variable-temperature 'H n.m.r. data. The
mannitol derivative (91) formed a weak complex with Bu'NH,' NCS- ( K , =
520 1 mol-') and a complex with PhCH2NH3+NCS-, stabilized yet again by a
dipole-induced-dipole interaction between the phenyl group and one of the
1,3-dioxan rings.93 Configurational restraints which lead to poor co-operativity
of non-covalent bonds at the primary binding site have been demonstrated in a
number of trans-transoid-trans 18-crown-6 ethers [e.g. the bis-glucoside (92),
where K , is <50 1 mol-' with ButNH3' NCS-].94 On the other hand, molecular
models indicate that the incorporation of a constrained 'diethylene glycol'
fragment into the 18-crown-6 constitution can lead to improved orientations of
oxygen atoms with respect to the bound cation. This has been convincingly
demonstrated with the 2,5 -anhydro-D-mannitol derivative (93), in which K , is
250 000 1 mol-' for the complex with Bu'NH,' NCS-.95
(91)
Ph (92)
(0 0 01
0
ko$
Me OMe
(94)
J 6
(93)
Thermodynamic parameters relating t o the binding of cations with a wide range
of crown and crown have been published.
Crown ethers have recently been shown to form crystalline, strictly
stoicheiometric addition compounds with hexasubstituted benzene derivatives,
e.g. (94), which are suited for systematic investigations of intra- and inter-
93 D. A. Laidler and J. F. Stoddart, Tetrahedron Lett., 1979, 453.
94 D. A. Laidler, J. F. Stoddart, and J. B. Wolstenholme, Tetrahedron Lett., 1979, 465.
'' J. A. Haselgrave, J. F. Stoddart, and D. J . Thompson, Tetrahedron Lett., 1979, 2279.
" J. D. Lamb, R . M. Izatt, C. S. Swain, and J. J. Christensen, J. Am. Chem. SOC., 1980,102, 475.
" J. D. Lamb, R. M. Izatt, C. S. Swain, J. S. Bradshaw, and J. J. Christensen, J. Am. Chem. SOC.,
1980,
102,479.
molecular complexation between organic rn01ecules.~~

Proton n.m.r. data indi-
cate that dibenzo-18-crown-6 forms a 1: 1 complex with water dissolved in
CHC13.99
E. Weber, W. M. Mueller, and F. Voegtle, Tetrahedron Lett., 1979, 2335.

99 K. B. Yatsimirskii, L. I. Budarin, A. I. Telyatnik, and Z . A. Gavrilova, Dokl. Akad. Nauk SSSR,
1979, 246, 691 (Chem. Abstr., 1979,91, 107 349).
7
Bridged Systems
BY J. M. MELLOR
1 Introduction
This chapter covers the period July 1979 to June 1980. In this period a
considerably greater number of publications concerned bridged oxygen com-
pounds. The rate of publication in other areas has changed little, although
publications concerning decomposition of bridged azoalkanes have been prolific.
Cyclophane chemistry attracts much interest. Heterosubstituted cyclophanes
occupy a position as key intermediates in the synthesis of carbocyclic cyclo-
phanes, and their chemistry is not discussed here. The chemistry of such
heterosubstituted cyclophanes has been reviewed,’ and is the subject of many
recent papers, particularly from the group of Newkome.2
2 Reviews
A general review3 of ‘new types of heterocyclic compounds’ has a section on
bridged systems. Two areas of recent interest, i. e. decomposition of azoalkanes4
and cyclic polyepoxide~,~ which are often prepared from bridged peroxides, have
been reviewed. The interest in the chemistry of crown ethers is well established,
but a stimulating review by Lehn6 points the way forward in this field, beyond
molecular recognition based on selective binding, to the concepts of catalysis and
of transport processes - including electron transport. The exciting use of carbo-
hydrates’ as building blocks to create chiral crown ethers to act as receptors
has been reviewed.
The balance between the controlling influence of steric effects and secondary
orbital interactions in the chemistry of heterosubstituted propellanes’ has been
analysed. In a discussion of intramolecular interactions in a variety of systems,
Leonard’ probes the unusual hybridization of 1-azabicyclo[3.3.3]undecane (1)
’ F. Vogtle and G . Hohner, Top. Curr. Chem., 1978,14, 1; V. Boekelheide, Acc. Chem. Res., 1980,
13,65.
G. R. Newkome and T. Kawato, J. A m . Chem. SOC.,1979,101,7088.
T. Sasaki, Heterocycles, 1979, 13,531.
P. S. Engel, Chem. Rev., 1980, 80,99.
W. Adam and M. Balci, Tetrahedron, 1980, 36, 833.
J. M. Lehn, Pure Appl. Chem., 1979,51,979.
J. F. Stoddart, Chem. SOC.Rev., 1979, 8, 85.
* R. Gleiter and D. Ginsburg, Pure Appl. Chem., 1979,51, 1301.
N. J. Leonard, Acc. Chem. Res., 1979, 12,423.
381
('manxine') and related compounds. A review l o of stereochemical features of

organophosphorus compounds includes sections on bridged systems.
The justification of much of the chemistry directed to the synthesis of bridged
systems concerns the applications of compounds having interesting biological
properties in the fields of insect chemistry or medicinal chemistry. The tropane
alkaloids, morphine alkaloids, amaryllidaceae alkaloids, and indole alkaloids
have been discussed, and the elegant use of cycloaddition reactions of nitronesl*
to afford, in particular, tropane alkaloids has been reviewed. The analgesic
activity of bridged amines has stimulated a continuing interest in their synthesis.
Both general reviews on the use of Diels-Alder reactions with irninesI3 and the
reaction of dienophiles with h e t e r o a r e n e ~and
l ~ a review of methods of synthesis
of 2-azabicyclo[3.3.l]nonanes" have been published. In reviewing the applica-
tions of stereo-control in the synthesis of natural products, Bartlett16 comments
on the synthesis not only of alkaloids but also of certain aggregation pheromones.
Bredt's Rule is further assessed in a report by Shea," which covers both
carbocyclic and heterocyclic bridged systems.
3 Physical Methods
X-Ray and Neutron Diffraction.-X-Ray studies have been reported for
arsatriptycene (2)" and phosphatriptycene (3)," and also for substituted arsatrip-
tycenes" and phosphatriptycenes.20The structures of the [4 + 21 cyclo-adduct
(4) and the [6 + 41 cyclo-adduct (5) of N-ethoxycarbonyl-lH-azepinewith
I
E = C02Me (5) COZEt
In B. E. Maryanoff, R. 0. Hutchins, and C. A. Maryanoff, Top. Stereochem., 1979, 11, 187.

" 'The Alkaloids', ed. M. F. Grundon (Specialist Periodical Reports), The Chemical Society, London,
1979, Vol. 9 , p p . 46, 115, 137, and 151.
l 2 J. J. Tufariello, Acc. Chem. Res., 1979, 12, 396.
l 3 S. Weinreb and J. I. Levin, Heterocycles, 1979, 12, 949.
l 4 T. Wagner-Jauregg, Synthesis, 1980, 165.
l 5 J. Bosch and J. Bonjoch, Heterocycles, 1980, 14, 505.
l 6 P. A. Bartlett, Tetrahedron, 1980, 36, 1.
K. J. Shea, Tetrahedron, 1980, 36, 1683.
F. J. M. Freijee and C. H. Stam, Acta Crystallogr., Sect. B, 1980, 36, 1247.
I 9 C . van Rooyen-Reiss and C . H. Stam, Acta Crystallogr., Sect. B, 1980,36, 1252; F. Smit and C. H.
Stam, ibid., p. 1254.
'"N. van der Putten and C. H. Stam, Acta Crystallogr.. Sect. B, 1980, 36, 1250.,
Bridged Systems 383
and of the photo-

2,5-dimethoxycarbonyl-3,4-diphenylcyclopentadien0ne~~
adduct (6) of furan with 1-cyanonaphthalene have been defined by X-ray
methods.22Cycloaddition of furan with fumaryl ~hloride~~,proceeds in good yield
and makes the bromo-lactone (7) readily available. The X-ray structural determi-
nation23 of (8),obtained uia several steps from (7), has been reported. [2,3]
Sigmatropic rearrangement of the ylide (9) the vinyl ether (lo), which
was characterized by X-ray analysis. Further studies concern 4-(trimethylstan-
ny1)quinuclidinium p e r ~ h l o r a t e , ~3-ethyl-3-azabicyclo[3.2.l]octane-8-spiro-
~
5’-hydant0in,~~ and 1-bromo-3,5,7-trimethyl- 1,3,5,7-tetra~ila-adamantane.~’
The conformational equilibria in bicyclo[3.3. llnonanes have attracted much
attention, and a variety of techniques have been used for studies in solution (see
below for recent studies), but X-ray analysis has been frequently used to study
conformations in the solid state. Energy differences in this series are sufficiently
small that different conformations may be adopted in solution and in the crystal.
Structures have now been reported2’ for eleven bicyclo[3.3. llnonanes, including
a number of heterocyclic examples. In most cases the chair-chair structure is
adopted in the crystal, but examples have been found for preference of the
chair-boat structure.
Further X-ray analyses have been reported in later references (refs. 58, 67,
105, 108, 121, 155, and 191).
21
K. Harano, T. Ban, M. Yasuda, and K. Kanematsu, Tetrahedron Lett., 1979, 1599.
22
K. Kan, Y.Kai, N. Yasuoka, and N. Kasai, Bull. Chem. SOC.Jpn., 1979, 52, 1634.
23
C. L. D. Jennings-White, A. B. Holmes, and P. R. Raithby, J. Chem. Soc., Chem. Commun., 1979,
542.
24
0. H. Johansen, P. Groth, and K. Undheim, Acta Chem. Scand., Ser. B, 1980,34, 1.
25
M. Zehnder, Helv. Chim. Acta, 1980, 63, 750.
26
P. Smith-Verdier, F. Florencio, and S . Garcia-Blanco, Acta Crystullogr., Sect. B, 1979, 35, 1911.
27
S. N. Gurkova, A. I. Gusev, V. A. Sharapov, T. K. Gar, and N. V. Alekseev, Zh. Strukt. Khim.,
1979, 20, 356.
28
S. K. Bhattacharjee and K. K. Chacko, Tetrahedron, 1979, 35, 1999.
3 84 He teroc y c Eic Chemistry
Photoelectron Spectroscopy and Related Electrochemical Studies.-In a con-

tinuation of their studies of the conformational analysis of tetra-alkylhydrazines,
~ ~bridged hydrazines (11)-(15) by 13C
the Wisconsin group have a n a l y ~ e dthe
n.m.r., photoelectron spectroscopy (p.e.s.), and cyclic voltammetry. Within this
series, the measurement of E” values by cyclic voltammetry is relatively uninfor-
mative with respect to conformation. Again the interpretation of the p.e.s. results
is complex, but dynamic I3C n.m.r. studies have clearly shown that (15) adopts
only the endo-cis-fused conformation whereas (11)-(13) are trans-fused.
3;
NJ &N
,,
(12) X =
L X
CH2CH2
(;h y
’ j4 / \
-
\
(11) n = 2
(13) n = 1 (15) X = CEt2 (14) (16)
The important synthetic chemistry resulting in the ready availability of cyclic

peroxides has led to p.e.s. studies of a number of these compounds. Information
concerning conformation is available. For example, AE, the energy difference
between the first two ionization potentials of peroxides, can be related3’ to the
0-0 torsional angle 4 by the equation AE/eV=2.08cos~#1+ 0.15. Further
aspects of peroxides are discussed below.
The spectrum of the ether (16) has been compared3’ to those of other
tetramethylenenorbornanes.
Nuclear Magnetic Resonance Spectroscopy.-As noted above, conformational
analysis of bicyclo[3.3. llnonanes is still a topic of considerable interest. A
variable-temperature I3C n.m.r. analysis3* now provides the first case in which
the boat-chair-chair-boat equilibrium is directly observed in the amines (17) and
(18). In a related case, re-examination of the acetal (19) that the
preferred conformation involves a chair carbocyclic ring and a boat heterocyclic
ring. This conclusion was made by ‘H n.m.r. analysis, using lanthanide shift
reagents, by a study of nuclear Overhauser effects, and by measurement of
relaxation times of protons. Details have been for other 3-
azabicyclo[3.3.l]nonanes, and the n~n-additivity~’ of substituent effects on 13C
chemical shifts in 9-thiabicyclo[3.3.l]non-2-eneshas been analysed. Both 13C
and “B n.m.r. data have been reported36for a series of 9-borabicyclo[3.3.1]non-
anes and their pyridine complexes.
29 S. F. Nelson, W. C. Hollinsed, L. A. Grezzo, and W. P. Parmelee, J. Am. Chem. SOC., 1979,101,
7347.
30 P. Rademacher and W. Elling, Liebigs Ann. Chem., 1979, 1473; P. Rademacher, Angew. Chem.,
Int. Ed. Engl., 1979, 18, 826.
31 M. Mohraz, C. Batich, E. Heilbronner, P. Vogel, and P. A. Carrupt, Red. Trav. Chim. Pays-Bas,
1979,98, 361.
32 Y. Takeuchi, P. Scheiber, and K. Takada, J. Chem. SOC.,Chem. Commun., 1980,403.
33
J. A. Peters, W. M. M. J. Bovee, P. E. J. Peters-Cranenburgh, and H. van Bekkum, Tetrahedron
Lett., 1979, 2553.
34 G. G. Trigo, M. Espada, and E. Galvez, J. Heterocycl. Chem., 1980, 17, 599.
35
J. W. de Hann, L. J. M. van de Ven, H. Vlems, M. M. E. Scheffers-Sap, H. Gillissen, and H. M.
Buck, Tetrahedron, 1980, 36,799.
36 H. C. Brown and J. A. Soderquist, J. Org. Chem., 1980, 45, 846.
Bridged Systems 385
Lanthanide-induced shifts in the 'H and 13Cn.m.r. spectra of the sulphoxides

(20) and (21)37and in spectra of a number of bridged a z o ~ y - a l k a n e sand
~ ~ 13C
n.m.r. data of 1,4-epo~ydecahydronaphthalenes~~ have been reported.
(17)R=Me (19) (20) exo-sulphoxide

(18) R = But (2 1) endo-sulphoxide
Miscellaneous Methods.-The one-electron reduction of the dication (22) has

been reported4' earlier. Now the synthesis4*of the dication (23), discussed more
fully below, has been described, and the relative lifetimes of cation radicals
derived from (22) and (23) have been compared4*with those of the cation radical
obtained from the dication (24).Reduction of the cations (22)-(24) was achieved
+N-N+
Me
(22) (23) (24)
by using solvated electrons, generated by pulse radiolysis, and the formation of

the cation radicals could be detected by the growth of signals at -475 nm. The
bridged cation radicals are substantially longer lived, whereas cleavage of the
N-N bond in the ion radical from (24) is rapid and irreversible. The delocaliz-
ation of the odd electron in (25), which is the cation radical derived from
1,4-diazabicyclo[2.2.2]octane, is well established. A comparison has now been
made43with the radical (26), generated from the bromide by photochemically
produced Me3!%-. Spectroscopic (e.s.r.) and kinetic evidence has established that
in radical (26) the spin is not delocalized to the nitrogen atom. Nitrogen-14
nuclear quadrupole relaxation have been made with 1,4-diaza-
bicyclo[2.2.2]octane.
37 D. J. H. Smith, J. D . Finlay, C. R. Hall, and J. J. Vebel, J. Org. Chem., 1979, 44,4757.

38 W. H. Bearden, R. Davis, M. R. Willcott, and J. P. Snyder, J. Org. Chem., 1979, 44, 1974.
39 C . B. Rose and S. K. Taylor, J. Heterocycl. Chem., 1979, 16, 705.
40 R. W. Alder, R. B. Sessions, J. M. Mellor, and M. F. Rawlins, J. Chem. SOC.,Chem. Commun.,
1977,747.
4' R. W. Alder and R. B. Sessions, J. A m . Chem. SOC., 1979,101, 3651.
42 S. F. Nelson, R. W. Alder, R. B. Sessions, K.-D. Asmus, K . - 0 . Hiller, and M. Gobl, J. A m . Chem.
SOC., 1980, 102, 1429.
43 S . Bank, W. K. S. Cleveland, D. Griller, and K. U. Ingold, J. A m . Chem. SOC.,1979,101, 3409.
44 H. Negita, M. Maekawa, T. Kubo, and T. Okuda, Bull. Chem. SOC. Jpn., 1979,52, 1205.
Values of pK, have been for 42 quinuclidinium perchlorates in a

further analysis of the reliability of inductive substituent constants.
4 Systems containing Nitrogen

Synthesis.-Emphasis is again placed on new methods that lead to bridged
compounds. The more routine studies, leading to compounds having important
physiological activity, are little discussed. Reference elsewhere46 is recom-
mended.
Synthesis by Cycloaddition. Earlier reports h.ave shown that acylnitroso-com-
pounds add efficiently to dienes. Now a full paper describes4’ the oxidation of
hydroxamic acids to give acylnitroso-compounds which can act both as
dienophiles or as hetero-dienes with respect to cyclopentadiene. Heating the
bridged oxazine adducts causes partial rearrangement to dioxazines (Scheme 1).
Scheme 1
4s C. A. Grob, B. Schaub, and M. G. Schlageter, Helv. Chim. Acta, 1980,63,57.
46 2-Azabicyclo[3.2.l]octanes: H. H. Ong, V. B. Anderson, J. C. Wilker, T. C. Spaulding, and L. R.
Meyerson, J. Med. Chem., 1980,23,726.
6-Azabicyclo[3.2.l]octanes: H.Tomisawa, H. Kato, R. Fujita, and H. Hongo, Chem. Pharm. Bull.,
1979,27,392;H.Tomisawa, H.Hongo, H. Kato, T. Naraki, and R. Fujita, ibid., p. 670.
8-Azabicyclo[3.2.l]octanes: G. G. Trigo, C. Avendano, E. Santos, J. T. Edward, and S. C. Wong,
Can. J. Chem., 1979,57, 1456;G.G.Trigo, C. Avendano, and E. Santos, A n . Quim., 1979,75,
761;S. P.Singh, D. Kaufman, and V. I. Stenberg, J. Heterocycl. Chem., 1979,16,625.
l-Azabicyclo[2.2.2]octanes: P. H. Nelson, A. M. Strosberg, and K. G. Untch, J.Med. Chem., 1980,
23, 180.
2-Azabicyclo[2.2.2]octanes: M.Longobardi, P. Schenone, and F. Bondavalli, Farmaco, Ed. Sci.,
1979,34,331,383.
l-Azabicyclo[3.3.l]nonanes: J.-P. Maffrand, F. Eloy, and M. Lucas, Heterocycles, 1980,14,321.
9-Azabicyclo[3.3.l]nonanes: G.G. Trigo, C. Avendano, P. Ballesteros, and A. Sastre, J. Heterocycl.
Chem., 1980,17,103.
9-Azabicyclo[4.2.l]nonanes: M.A. Loreto, L. Pellacani, and P. A. Tardella, J. Heterocycl. Chem.,
1979,16,1233.
Anatoxin-a and isoanatoxin-a (9-azabicyclononenes): H. F. Cambell, 0. E. Edwards, J. W. Elder,
and R. J. Kolt, Pol. J. Chem., 1979,53, 27.
3,7-Diazabicyclo[3.3.l]nonanes: R. Caujolle and A. Lattes, C. R. Hebd. Seances Acad. Sci., Ser.
C., 1979,288,217.
2,4-Diazabicyclo[3.3.l]nonanes: W. Wendelin and W. Kern, Monatsh. Chem., 1979, 110, 861,
1213.
2,4,6,8-Tetra-azabicyclo[3.3.l]nonanes: V. A. Eres’ko, L. V. Epishina, 0. V. Lebedev, L. I.
Khmel’nitskii, S. S. Novikov, M. V. Povstyanoi, and A. F. Kulik, Izu. Akad. Nauk. SSSR, Ser. Khim.,
1979,1073.
47 K.H. Dao, J. M. Dust, D. Mackay, and K. N. Watson, Can. J. Chem., 1979,57,1712.
Bridged Systems 3 87
Supplementary information concerning the 1,4-cycloaddition of nitrosoben-

zene to N- (ethoxycarbonyl)azepine4* is now available. A new adduct (27) has
been reported. D e c o m p ~ s i t i o nof~ ~the known adduct (28) in the presence of
alkenes leads to the formation of N-substituted hydroxamic acids in high yield.
The procedure gives an effective method of allylic amidation.
A very spectacular synthesis5’ of bridged aza[lO]annulenes is shown in Scheme

2. Good yields of stable annulenes are obtained from triazines carrying several
electron-withdrawing substituents. In the case of less reactive triazines, reaction
Scheme 2
could only be achieved at high pressures. Addition of triazines to c y c l ~ p r o p e n e s ~ ~

leads to 4H-azepine mono-adducts, which further react via their 3-azanor-
caradiene valence isomers to give bis-adducts; e.g., (29) from cyclopropene.
Bridged bis-adducts are obtained5’ from polyhalogeno-triazines and alkenes.
Ph
Cycloaddition of maleic anhydride to N-substituted pyridones has been used

in a synthesiss3 of a 2-azabarrelene (Scheme 3). A key step is anodic oxidation
of an intermediate dicarboxylic acid, which affords 2-azabarrelenone in 6-8%
48 W. S. Murphy and K. P. Raman, Tetrahedron Lett., 1980, 21, 319.

49 G . E. Keck and R. R. Webb, Tetrahedron Lett., 1979, 1185; G . E. Keck and J. B. Yates, ibid., p.
4527.
’O M. L. Maddox, J. C. Martin, and J. M. Muchowski, Tetrahedron Lett., 1980, 21, 7.
” U. Gockel, U. Hartmannsgruber, A. Steigel. and J. Sauer, Tetrahedron Lett., 1980,21, 599.
’* M. G. Barlow, R. N. Haszeldine, and D. J. Simpkin, J. Chem. SOC.,Chem. Commun., 1979,658.
53 R. Gompper and A. Schmidt, Angew. Chem., Int. Ed. Engl., 1980, 19,463.
0
Do I
CH,Ph
-
I
--+
phc&
ii, iii
__+ phc&co,"
CO,H
0
1 iv
CO,H
Reagents: i, maleic anhydride; ii, OH ; iii, H,O'; iv, Na, NH,; v, anodic oxidation; vi, Me,O' BF,-
Scheme 3
yield. High pressures facilitate c y ~ l o a d d i t i o nof~ ~dimethyl acetylenedicarboxy-

late to 2(1H)-pyridones, but moderate yields may be obtained at normal press-
ures in certain cases.55Adducts of N-phenylmaleimide with pyridinethiones have
been reported.s6
As a route to the cis-hydroisoquinoline moiety of reserpine-type indole
alkaloids, further additions to dihydropyridines have been investigated. Follow-
ing successful [4 + 21 c y ~ l o a d d i t i o nto~acrolein,
~ subsequent elaboration permit-
ted selective generation of the required stereochemistry by Cope rearrangement
(Scheme 4).Investigations5' aimed at the synthesis of Erythrina alkaloids have
t
E = COzMe
Reagents: i, acrolein; ii, Ph,PCHCO,Me; iii, heat
Scheme 4
shown that thermolysis of the enamine (30) gives (31) by intramolecular [4 + 21
cycloaddition. The identity of (31) was established by its hydrogenation to give
(32), whose structure was proved by X-ray analysis. In a similar manner, the
enamide (33)underwent cycloaddition. Vapour-phase thermolysisS9of the ether
54 K. Matsumoto, Y . Ikemi-Kono, T. Uchida, and R. M. Acheson, J. Chem. SOC., Chem. Commun.,
1979, 1091.
55 G. P. Gisby, S. E. Royall, and P. G. Sammes, J. Chem. SOC.,Chem. Commun., 1979, 501.
56 N. P. Shusherina, V, S. Pilipenko, and L. V. Betaneli, Zh. Org. Khim., 1979, 15, 1277.
57 P. A. Wender, J. M. Schaus, and D. C. Torney, Tetrahedron Lett., 1979,2485.
5n S. F. Martin, T-S. Chou, and C.-Y. Tu, Tetrahedron Lett., 1979, 3823.
59 G. M. Brooke, R. S. Matthews, and N. S. Robson, J. Chem. SOC.,Perkin Trans. 1, 1980, 102.
Bridged Systems 389
1025 (30) X = H2
1026 (33) x = 0 (31) (32)
(34) afforded (35) via internal cycloaddition of the Claisen rearrangement
intermediates. Similarly, (36) gave (37) in 81 % yield. Photoaddition6' of alkenes
to pentafluoropyridine gives bath [2 + 21 and [4 + 21 cyclo-adducts.
(34) R1 = F,R2 = OCH2CH=CH2 (35) X = N , Y = CF

(36) R' = OCH2CH=CH2, R2 = F (37) X = CF,Y = N
Some [4 + 21 cycloadditions of aromatic substrates are shown in Scheme
5.6164 By Oxidation of (38) with peracids,61 the nitrogen bridge is lost as
@:: + MeN$ &

\
Me
Ref. 61
o:r &
(38)
NC0,Bu'
+ But02CNb A I \ Ref. 62
Br x
\ -&
iii
NC0,Me
NC0,Me
I
Ref. 63
Reagents: i, BuLi, THF, at -78°C; ii, Mg, THF; iii, MeO,CN=NCO,Me,

+tzb Ref. 64
ZnlCu couple, DMF;

iv, furan
Scheme 5
bu M. G . Barlow, D. E. Brown, R. N. Haszeldine, and J. R. Langridge, J. Chem. Soc., Perkin Trans.
1, 1980, 129.
" H. Hart and A. Teuerstein, Synthesis, 1979, 693.
'' E. Chacko, J. Bornstein, and D. J. Sardella, Tetrahedron, 1979,35, 1055.
h3 W. R. Dolbier, K. Matsui, L. McCullagh, and K. E. Anapolle, J. Org. Chem., 1979, 44, 2842.
nitrosomethane, affording octamethylnaphthalene in satisfactory yield. Conven-

tional conversion63 of (39) into the corresponding azoxy-derivative permitted
subsequent thermal or photochemical generation of isoindenes. A systematic
concerns cycloaddition of (40) not only with furan but also with tropone,
tropolone, and fulvenes. P h ~ t o r e a r r a n g e m e n tof
~ ~these adducts gives keten
intermediates, which were trapped as esters. Further cycloadditions of
isoquinolinium salts66and an X-ray analysis67of adducts of triazolinediones with
propellanes are noted.
[6 + 31 Cycloadditions68 whereby 1,l- and 1,3-dipheny1-2-aza-allyl-lithium
add to cycloheptatriene have been reported. In the former case a single adduct
(41) was isolated, in 47% yield, and in the latter case the epimers (42) and (43)
were obtained. The pyrazinone (44) is photostable in benzene or methanol
~ ~ the single [4 + 41 cyclo-adduct (45) quantitatively
solution, but i r r a d i a t i ~ ngives
in the solid state.
(41) R' = R2 = P h , R 3 = R4 = H
(42) R' = R3 = H , R 2 = R4 = Ph (44) (45)
(43) R 1 = R4 = H , R 2 = R3 = Ph
A .number of full papers concerning the continuing saga of the cycloaddition

reactions of 3-oxidopyridinium betaines have been published by Katritzky and
his group. One theme has been the use of different N-substituted derivatives with
the intention that, following cycloaddition of the betaine, removal of the sub-
stituent on nitrogen might be facilitated. Hence, using P-aroylvinyl substitution,
e.g. as in (46j, cycloaddition of styrene might give an intermediate that can be
hydrolysed to afford the simple bicyclic amine (47). In the event, (46) and related
betaines undergo7' the expected cycloadditions, but a route to (47), and hence
to tropoiles, is frustrated by the isolation of diiners of (47). In an alternative
a p p r ~ a c h ,N-
~ ' ( 2-pyridyl) and related betaines were prepared, and additions with
different dipolarophiles investigated. In this case, subsequent quaternization led
to ring-opening, and the formation of a tropone has been reported. In a further
approach, the of 3-hydroxypyridine with acrylonitrile or methyl acry-
late gives adducts, e.g. (48),with involvement of two moles of dipolarophile. In
64 T. Sasaki, T. Manabe, and S. Nishida, J. Org. Chem., 1980, 45, 476.
65 T. Sasaki, T. Manabe, and E. Wakabayashi, Tetrahedron, 1980, 36T2119.
66 T-K.Chen and C. K. Bradsher, J. Org. Chem., 1979,44,4680.
67 M. Kaftory, M. Peled, and D . Ginsburg, Helv. Chim. Acta, 1979, 62, 1326.
68 D . . Bower and M. E. H. Howden, J. Chem. SOC.,Perkin Trans. 1, 1980, 672.
I.
69 T. Nishio, N. Nakajirna, and Y. Ornote, Tetrahedron Lett., 1980, 21, 2529.
'' A. R. Katritzky, S. Rahirni-Rastgoo, G. J. Sabongi, and G . W. Fischer, J. Chem. SOC.,Perkin Trans.
I, 1980, 362; A. R. Katritzky, M. Abdallah, S. Bayyuk, A. M. A. Bolouri, N . Dennis, and G. J.
Sabongi, Pol. J. Chem., 1979, 53, 57.
" A. R. Katritzky, A. Boonyarakvanich, and N. Dennis, J. Chem. SOC., Perkin Trans. 1, 1980, 343.
72
A. R. Katritzky, J. Banerji, N. Dennis, J. Elison, G. J. Sabongi, and E. U. Wurthwein, J. Chem.
SOC.,Perkin Trans. I, 1979, 2528.
Bridged Systems 391
no-
3 @
N
Me, C,+,N
&fc*04-
,-,,,
Ar 0 Ph CN
(46) (47) (48)
this case, subsequent elaboration to tropolones is more successful, and overall
yields of -25 YO from 3-hydroxypyridine have been reported.
A further synthetic aspect is the reaction73 of some dimers of 3-
oxidopyridinium betaines with dienamines to give bridged adducts (Scheme 6).
R
E
Reagents: i, H,C=CHCH=CHNMe,
Scheme 6
The reaction of betaine monomers with dichloroketen and related ketensT4is by

[8 + 21 cycloaddition. Further photo addition^^' of these betaines have been
reported.
The interesting t r a n ~ f o r m a t i o nof~ ~pyrazines into bridged amines by related
cycloadditions has been reported (Scheme 7). The reaction, which proceeds
effectively with both acetylenes and electron-deficient alkenes, must involve a
dipolar addition.
Scheme 7
Recent intramolecular cycloadditions of nitrones have been effectively used in
the synthesis of alkaloids. Further example^'^ of the synthetic utility of nitrone
additions are given in Scheme 8.
73 A. R. Katritzky, N. Dennis, and H. A. Dowlatshahi, J. Chem. SOC.,Perkin Trans. 1, 1980, 331.
74 A. R. Katritzky, A. T. Cutler, N. Dennis, G. J. Sabongi, S. Rahimi-Rastgoo, G. W. Fischer, and
I. J. Fletcher, J. Chem. SOC.,
Perkin Trans. 1, 1980, 1176.
” A. R. Katritzky, S. I. Bayyuk, N. Dennis, G. Musumarra and E.-U. Wurthwein, J. Chem. SOC.,
Perkin Trans. 1, 1979, 2535.
76 M. E. K. Cartoon, G. W. H. Cheeseman, H. Dowlatshahi and P. Sharma, J. Chem. SOC., Perkin
Trans. 1, 1980, 1603.
77 W. Oppolzer, S. Siles, R. L. Snowden, B. H. Bakker, and M. Petrzilka, Tetrahedron Left., 1979,
4391.
n =0 0% 76 Yo
n = 1 95% 00,0]
n = 2 68% 23 '/o
Scheme 8
Synthesis by Cyclization with Nucleophilic Nitrogen. The unusual bridged amine
(49) shows exceptionally low basicity, from which it has been concluded'* that
it adopts a conformation with the lone pair pointing internally, and hence hidden
from external influences. In accord with this conclusion, it fails to form hydrogen-
bonds with phenol, and the U.V. spectrum is almost the same in 2,2,4-trimethyl-
pentane and in ethanol-water. The synthesis of the amine (49) is shown in
Scheme 9.
Reagents: i, PhO(CH,),MgBr; ii, HBr; iii, Ag,O, H,O; iv, HBF,; v, Na, NH,
Scheme 9
Many syntheses of tropanes proceed by nucleophilic addition of amines to
cyclohepta-2,6-dienones. A ~ a r i a t i o n 'of
~ this method, by starting with a sub-
stituted cyclohexenone, permits the synthesis of novel tropanes. Such a transfor-
mation of carvone (SO)is shown in Scheme 10.
0
I II
78
'9
Scheme 10
i i i , iv
e--
R. W. Alder and R. J. Arrowsmith, J. Chem. Res. (S), 1980, 163

T. L. Macdonald and R. Dolan, J. Org. Chem., 1979, 44, 4973.
P
Reagents: i, Me,SiCI, Et,N, ZnCI,, PhH; ii, MeOCH,CH,OMe, CCI,C02Na; iii, MeNH,; iv, Bu,SnH
Bridged Systems 393
Unusual biological activity has been associated with a number of natural

products having guanidino functionality, e.g. in tetrodotoxin (the poison of the
puffer fish). With the purpose of investigating structure-activity relationships, a
number of bicyclic guanidines" have been synthesized (Scheme 11).
T~N'
Te + SMe
bNH2
'4
YN
H
--b H
kN
NTs
N d -+N
NH, C1-
(a) R = H,; (b) R = 0

n0
\ /
Scheme 11
The synthesis of benzomorphans and related analgesics has been In

Scheme 12,s1-s4 preparations of related skeletons are collected. The synthesiss5
C0,Et
_L
1
Ref. 81
I
Reagents: i, PPA; ii, NBS; iii, CuBr; iv, EtNH,; v, RNH,, NaCNBH,
Scheme 12 (part)
R. A. Houghton, R. A. Simpson, R. N. Hanson, and H. Rapoport, J. Org. Chem., 1979,44,4536.

M. Lennon and G. R. Proctor, J. Chem. SOC.,Perkin Trans. 1 , 1979, 2009.
82 M. Curphey, M. Lennon, E. Murphy, and G. R. Proctor, J. Chem. SOC.,Perkin Trans. I, 1979,2013.
83 M. E. Christy, P. S. Anderson, S. F. Britcher, C. D. Colton, B. E. Evans, D. C. Remy, and E. L.
Engelhardt, J. Org. Chem., 1979,44, 3117.
84 €3. E. Evans, P. S. Anderson, M. E. Christy, C. D. Dolton, D. C. Remy, K. E. Rittle, and E. L.
Engelhardt, J. Org. Chem., 1979,44, 3127.
85 M. J. Haire, J. Org. Chem., 1980, 45, 1310.
NHMe
Ref. 84
Br
Ref. 84
Reagents: vi, heat; vii, MeNH,

Scheme 12 (cont.)
of (5l),having the previously unprepared dibenzo-azasemibullvalene skeleton,
a
is shown in Scheme 13.
,NO2 NOH
\ / H
N
0 0
H
N
OH
IV
t
I
0
OMe
(5 1)
Reagents: i, SnCl,, HC1, THF; ii, LiAlH,, Et,O; iii, KMnO,; iv, MeSO,CH,Na, DMSO, Me1
Scheme 13
Procedures for the conversion of the readily available nitrile (52) into 4-aza-
hornoadamantanes,86 e.g. (53), and alternative procedures, avoiding the use of
mercury salts, for the conversion8’ of pinenes into 1-aza-adamantanes are noted.
Synthesis by Other Cyclization Reactions. Rearrangement of intermediates

generated by photolysis of azides has provided an important route from 1-
azidoadamantane to aza-homoadamantanes. Now full details have been given
86 A. Hassner, T. K. Morgan, and A. R. McLaughlin, J. Org. Chem., 1979,44, 1999.
87 A. Pancrazi, I. Kabore, B. Delpech, and Q. Khuong-Huu, Tetrahedron Left.,1979, 3729.
Bridged Systems 395
for preparation of aza-homoadamantenes from 2-azido-adamantanes. Thus

photolysisX8of (54) gives (55) as the major product. A potentially very important
synthesis of aza-homoadamantanes is provided by the decomposition of 1-
a~idoadamantane~' in the presence of aluminium chloride and aromatic sub-
strates. Intermediacy of an imine is probable in the formation of (56) and its
analogues as products. Acid-catalysed rearrangement'" of some spirocyclo-
hexadienones provides a novel synthesis of some unusual tricyclic structures
(Scheme 14).
C02H I
0
\\
Reagents: i, Pr'N=C=NPr'; ii, BF,

Scheme 14
A full paper'' describes the photoaddition of N-nitrosopiperidine to cyclo-

octa-1,5-diene. An intermediate adduct (57), after tautomerization, can undergo
acid-catalysed cyclization to give bridged hydroxylamines (58). Adducts with
nitrosyl chloride have similarly been reported, and evidence of the formation of
bridged nitroxides has been given. Photodecomposition92of the N-chloro-amide
(59) gave (60), in 43% yield, in model studies aimed at the synthesis of the
alkaloids gelsemicine and gelsedine, which incorporate the skeletal fragment
(60). Formation of the pyrrolidine (60) is highly selective, and the possible
formation of (61) is disfavoured.
X NOH
(57) ( 5 8 ) X = M e 0 o r CI
T. Sasaki, S. Eguchi, and N. Toi, J. Org. Chem., 1979,44, 3711.

89
D. Margosian, D. Sparks, and P. Kovacic, J. Chem. SOC., Chem. Commun., 1980,275.
90 K. Gubernator, W. Hofeditz, and H. Plieninger, Chem. Ber., 1980,113,669.
91 Y. L. Chow, K. S. Pillay, and H. Richard, Can. J. Chem., 1979,57, 2923.
92 S. W. Baldwin and R. J. Doll, Tetrahedron Lett., 1979, 3275.
The reaction93 of the dihydropyridine (62) with the sodium salt of acetyl-
acetone, in DMF, at 0 "C,gives the dihydroazepine (63).At higher temperatures,
(63) affords (64) in good yielh (Scheme 15). Direct C-alkylation by the enolate
anion of (63) is a 5-endo-trig process, and Baldwin's rule suggests that 0-
alkylation in (63) and failure to form (64) would be expected. However, the
disfavoured process may be avoided by a prior enamine-imine tautomerization,
permitting an alternative mode of cyclization. The reaction of (62) with sodium
hydrosulphide is known to give (65), but it has been shown that reaction
of thiourea with (62) gives (66). The formation of (66) is probably again via the
intermediacy o f an imine.
(63)
E = C02Me
Reagents: i, NaSH; ii, (MeCO),CHNa, DMF; iii, heat; iv, H,NCSNH,
Scheme 15
The addition9' of salts of /3- keto-esters to (67) at room temperature gave (68).
A route to modified benzomorphans is provided by Dieckmann c y c l i ~ a t i o nof~ ~
(69); after hydrolysis, this affords (70).
93 B. Gregory, E. Bullock, and T-S. Chen, J. Chem. SOC.,

Chem. Commun., 1%79, 1070.
94 M. E. M. Baggs and B. Gregory, Can. J. Chem., 1980,58,794.
95 E. Matsumura, M. Ariga, and Y. Tohda, Tetrahedron Lett., 1979, 1393.
96 K. Watanabe and T. Wakabayashi, J. Org Chem., 1980,45, 357.
Bridged Systems 397
0
Me CH,C02Me
(67) (69)
fi
Q 0 w
Routes to the novel cyclo[4.2.2]azinium salts9' are shown in Scheme 16.
CN
CN Me, N CN
Reagents: i, MeOH, NaCIO,; ii, EtOCH=CH,
Scheme 16
Reactions of Systems containing Nitrogen.-The low basicity of the mono-

amine (49) ~uggested'~ that the lone pair is directed internally in the most stable
conformation. Alder and his group at Bristol have also the chemistry
of the diamine 1,6-diazabicyclo[4.4.4]tetradecane (71). It is possible to envisage
97 W. Flitsch and E. R. Gesing, Tetrahedron Lett., 1979, 3405.

R. W. Alder, A. Casson, and R. B. Sessions, J. A m . :hem. SOC.,
1979, 101,3652.
a monoprotonated species from (71)in which the proton resides in the cavity or
an externally protonated species. Dissolving (71) in acids leads to external
protonation. Internal protonation is exceptionally difficult to achieve, but occurs
in strongly acidic media (e.g. CF,SO,H in MeCN). The resultant internally
protonated species is most reluctant to lose the proton. For example, deproton-
ation is not observed on heating with hydroxide salts. Clearly, the kinetics of
proton transfer to and from the internal position are most unfavourable.
A full paper describes the studies" of the Wisconsin group on the properties
of derivatives of 9-azabicyclo[3.3.l]nonane. Photoelectron spectroscopy has
been used to deduce the degree of flattening about the nitrogen atom and cyclic
voltammetry to show the unusual stability of cation radicals in this series. Proton
loss from the cation radical is disfavoured because of the constraints associated
with Bredt's rule.
Decomposition of (72)in ethanolic sodium hydrosulphite generates, in situ, an
azine which fragments to give nitrogen and cyclo-octatetraene. The yield of
cyclo-octatetraene is substantially lower than the yield of cyclo-octadiene from
(73).The controversy concerning the origin of this result continues. Anastassiou
has re-affirmed'"" the view that there is symmetry-controlled opposition to a
linear cheletropic process in (72)but not in (73).
(72) (73) (74)

( 7 5 )h2
The reaction of amines (74) and (75)with N-chlorosuccinimide has been
studied"' under conditions of kinetic control. The ratios of syn- and anti-N-
chloro-amines are substantially influenced by the nature of substituents in the
aromatic rings. It has reasonably been concluded that the product ratios are partly
controlled by electronic effects, but their nature has not been clearly established.
We note further studies concerning the ethano1ysis102 of 1-chloro-2-aza-
adamantanes, the rearrangement"" of N-chloro-tropanes, the d e a l k y l a t i ~ n ' "of~
(76) with PhSeH, the formation of a stable adduct between (77)and sulphur
d i o ~ i d e ' ' ~and also between aaa-trifluoroacetophenone and 1,4-diazabicyclo-
octane,'06 and the use of (78)as an intermediate'"' in the synthesis of the
antifungal antibiotic aristeromycin (79), which is a carbocyclic analogue of
adenosine. The acid-catalysed cyclizationlo8of (80)gave (81); the structure of
the product was determined by X-ray analysis.
99
S. F. Nelsen, C. R. Kessel, and D. J. Brien, J. Am. Chern. Soc., 1980, 102, 702.
I on
A . G. Anastassiou, Tetrahedron Lett., 1979, 2775.
J. R. Malpass and M. P. Walker, J. Chem. Soc., Chem. Commun., 1979, 585.
lo* P. M. Starewicz, E. A . Hill, P. Kovacic, and A. R. Gagneaux, J. Org. Chem., 1979, 44, 3707.
F. M. Schell, R. N. Ganguly, K. S. Percell, and J. E. Parker, Tetrahedron Lett., 1979, 4925.
H. J. Reich and M. L. Cohen, J. Org. Chem., 1979, 44, 3148.
Io5 G. J. Kubas, A. C. Larson, and R. R. Ryan, J. Org. Chem., 1979, 44, 3867.
M. L. M. Schilling, H. D. Roth, and W. C. Herndon, J. A m . Chem. Suc., 1980, 102, 4271.
lo' A. K. Saksena, Tetrahedron Lett., 1980, 21, 133.
W. W. Paudler, R. L. Mahaffey, and J . L. Atwood, J. Org. Chem., 1979,44, 2498.
Bridged Systems 399
Hoa
j
: HO
(79)
OH
(80)
Bridged Azoa1kanes.-The uses of azoalkanes as precursors of biradicals and as

synthetic intermediates for the generation of highly bridged hydrocarbons are of
great topical i n t e r e ~ tThis
. ~ Report is mainly concerned with synthetic aspects.
Reports concerning the chemistry of biradicals that are produced by thermal or
photochemical methods or the synthesis of individual azoalkanes will not be
further discussed, but such studies concern (82)lo9and the alkylated derivatives
(83)110*111and (84),"O (85)-(91),"' (92),'12,113(93),113(94) and its analogues,114
(95),'15 (96),'16 (97) and (98),lI7and (99)-(1O2).ll8
( 8 5 ) R = Me
(82) (83) (841 (90) R = H
(91)R = CH=CH;?
(86) (87) (88) (89)

lo' S. L. Buchwalter and G. L. Closs, J. A m . Chem. Soc., 1979, 101, 4688.
N. J. Turro and J-M. Liu, Tetrahedron Lett., 1980, 21, 1299.
Ill P. S. Engel, C. J. Nalepa, R. A. Leckonby, and W-K. Chae, J. A m . Chem. SOC., 1979,101,6435;
P. S. Engel, R. L. Allgren, W-K. Chae, R. A. Leckonby, and N. A. Marron, J. Org. Chem., 1979,
44, 4233.
'12 C. D. Duncan, L. R. Corwin, J. H. Davis, and J. A. Berson, J. A m . Chem. Soc., 1980,102, 2350;
M. S. Platz and J. A. Berson, ibid., p. 2358.
R. K. Siemionko and J. A. Berson, J. A m . Chem. Soc., 1980, 102, 3870.
C. Gousetis and J. Sauer, Tetrahedron Lett., 1979, 1295; H. D. Fuhlhuber, C. Gousetis, J. Sauer,
and H. J. Lindner, ihid.,p. 1299.
W. Adam and 0.de Lucchi,J. A m . Chem. Soc., 1980,102,2109;I. Erden and M. Balci, Tetrahedron
Lett., 1980, 21, 1825; W. Adam, 0. de Lucchi, and I. Erden, Angew. Chem., Int. Ed. Engl., 1979,
18,468.
W. Adam, N. Carballeira, and 0. de Lucchi, J. A m . Chem. Soc., 1980,102, 2107; W. Adam and
0. de Lucchi, Tetrahedron Lett., 1979, 4367.
I. Erden and A. de Meijere, Tetrahedron Lett., 1980, 21, 1837.
R. Askani, T. Hornykiewytsch, W. Schwertfeger, and M. Jansen, Chem. Ber., 1980,113,2154.
(Y3
(92) R = Me (94) E = C 0 2 M e
(93) R = H
(97)
(100) 9,10-dihydro
(101) 2,3-dihydro
(102)2,3,9,10-tetrahydro
The use of azoalkanes as synthetic intermediates is illustrated in Schemes 17119

and 18.12' We also note the general method'21 of formation of azoalkanes via
intramolecular cyclization of unsaturated tosylhydrazones under acidic condi-
tions (Scheme 19). The reaction of (103) gave products of intermolecular
condensation. Structure (104) was established by X-ray analysis. Use of the
optically active triazolinedione ( 1 0 9 , derived from camphor, has enabledI2*the
synthesis of optically active 4,5-diazatwist-4-ene (106), and the absolute
H
(E = C02Me)
Reagents: i, MeCN, heat
Scheme 17
Reagents: i, MeCN, PhSO,CH=CH,; ii, Na(Hg)
Scheme 18
'I9 R. D. Little and G. W. Muller, J. A m . Chem. Soc., 1979, 101, 7129.

R. D. Little and L. Brown, Tetrahedron Lett., 1980, 21, 2203.
R. M. Wilson, J. W. Rekers, A. B. Packard, and R. C. Elder, J. A m . Chem. SOC.,1980,102, 1633;
R. M. Wilson and J. W. Rekers, ibid., 1979, 101, 4005; A. Padwa and H. Ku, Tetrahedron Lett.,
1979,4425.
lZ2 J. A. Jenkins, R. E. Doehner, and L. A. Paquette, J. A m . Chem. Soc., 1980, 102, 2131.
Bridged Systems 401
NHTs
Scheme 19
(107)
N=N
configuration of (106) was established. Force-field calculations have been

made123 to determine heats of formation and strain energies of a number of
bridged azoalkanes.
Little and Carroll have developed an electrochemical procedure124 for the
formation of azoalkanes (Scheme 20). Autoxidation of (107) gives'25 (108).
NCO,CH,CCl,
NCO ,CH CCl,,
Reagents: i, cathodic reduction, in DMF; ii, K,[Fe(CN),]
Scheme 20
5 Systems containing Oxygen

Synthesis.-By Cycloaddition. The Noyori cycloaddition of halogeno-ketones to
furans is now sufficiently well established to provide a firm base for the successful
synthesis of C-nucleosides. For example, the ketone (109) has been prepared'26
123 D. C. Crans and J. P. Snyder, Ckem. Ber., 1980,113, 1201.

124 R. D. Little and G. L. Carroll, J. Org. Ckem., 1979, 44, 4720.
125 S. F. Nelson and W. P. Parmelee, J. A m . Chem. Soc., 1980,102, 2732.
T. Sato, H. Kobayashi, and R. Noyori, Tetruhedron Lett., 1980, 21, 1971.
402 He terocyc 1ic Chemistry
in 86% yield from 3-methylfuran, and it has been successfully elaborated to give
substituted pyrimidine C-nucleosides. A key step in the synthetic scheme is a
Baeyer-Villiger transformation, which can (in principle) afford regio-isomeric
lactones. Further examples’27leading to C-nucleosides have been described. In
view of the importance of this Baeyer-Villiger approach, it is interesting to note
that the regioselectivity of this rearrangement is markedly influenced by the
effects of remote substituents. Thus the ratio of regio-isomers obtainedlZ8from
(110) is markedly different from that obtained from (111). In the series (112),
I 1
R OH
( 1 12)
the size of the alkyl group R again markedly influences the outcome of the
Baeyer-Villiger rearrangement. The critical factor is ons side red'^^ to be the
orientation of the lone pair of the hydroxyl group. Cycloaddition of ct-halo-
geno-ketones with furans under basic conditions130also gives 3-0x0-8-oxa-
bicyclo[3.2.l]oct-6-enes.
The following aspects of [4 + 21 cycloaddition to furans have been studied:
the use of di-t-butyl acetylenedicarboxylate as a d i e n ~ p h i l e , ’ ~thus ’ providing a
synthetic equivalent of acetylenedicarboxylic anhydride; the use of fumaryl
~ examples of intra-
~ h l o r i d e ; ’ ~additions to 3 , 4 - d i m e t h o ~ y f u r a n ; ’ ~and
molecular addition. 1 3 3
Miscellaneous Syntheses. More syntheses have been reported in which bridged
oxabicyclic compounds are used as synthetic intermediates to allow subsequent
stereospecific elaboration to give important natural products. Prostaglandins and
prostacyclins are the subject of a recent review,134and in particular thromboxanes
and carbathromboxanes are such targets. Recent syntheses include analogues of
prostaglandin E213’and of throm boxane AZ. The carbathromboxane analogue
(113) has been synthesized from prostaglandin A2 (114) in twelve in
which the oxygen bridge is constructed at the end by closure of a diol. In a
12’ T. Sato, M. Watanabe. and R. Noyori, Tetrahedron Lett., 1979, 2897; T. Sato, K. Marunouchi, and
R. Noyori, ibid., p. 3669; T. Sato and R. Noyori. Heterocycles, 1979, 13. 141; Tetrahedron Lett.,
1980,21, 2535.
12’ R. Noyori, T. Sato, and H. Kobayashi, Tetrahedron Left., 1980, 21, 1-569.
129 R. Noyori, H. Kobayashi, and T. Sato, Tetrahedron Lett., 1980, 21, 2573.
B. Fohlisch, W. Gottstein, R. Kaiser, and I. Wanner, Tetrahedron Lett., 1980,21,3005:P. Matzinger

and C. H. Eugster, Helu. Chim. Acta, 1979, 62, 2325.
13’ G. Weber, K. Menke, and H. Hopf. A n g e w . Chem., Znt. E d EngI.. 1979. 18, 483.
13’ E. McDonald, A. Suksamrarn, and R. D. Wylie, J. Chem. Soc., Perkin Trans. I , 1979, 1893; P. X.
Iten, A. A. Hofmann, and C. H. Eugster, Helv. Chim. Acta, 1979, 62, 2202; A. A. Hofmann, I.
Wyrsch-Walraf, P. X.Iten, and C. H. Eugster, ibid., p. 2211.
P. J. D e Clercq and L. A. van Royen, Synth. Cornrnun., 197Y, 9, 771.
’34 S. Moncada and J. R. Vane, J. Med. Chem., 1980, 23, 591.
13’ R. F. Newton, D. P. Reynolds, C. F. Webb, S. N. Young, Z . Grudzinski, and S M. Roberts, J.
Chem. Soc., Perkin Trans. 1, 1979, 2789.
”’ K. M. Maxey and G. L. Bundy, Tetrahedron I,ett., 1980, 21, 445.
Bridged Systems 403
OH OH
1113) (114)
different approach, (115) has been s ~ n t h e s i z e d ”from

~ trans- 2,4-pentadien-l-o1
by an early construction of the bicyclic skeleton and elaboration of (116). A
lengthy route138to the 6-oxabicyclo[3.l.l]heptane skeleton that is found in (113)
proceeds via Baeyer-Villiger oxidation of (117). An economical synthesis of
(118),which is a key intermediate in the synthesis of thromboxane BZ,from (119)
has been des~ribed.’’~ Much activity is directed towards the synthesis of amino-
cyclitols and amino-sugars, and again bridged intermediates can facilitate
stereospecific synthesis. The cyclitol validamine afford^'^" such a case.
Synthesis of those insect aggregation pheromones having bridged structures

may have important economic consequences. Multistriatin (120) is an aggrega-
tion pheromone of a European elm bark beetle. A stereoselective ~ynthesis’~’
has been reported from tartaric acid. A delightfully simple synthesis14* of
frontalin (121), a pheromone of the pine beetle, is by photolysis of heptane-2,6-
dione in methanol-titanium chloride. We also note further photochemical studies
R3R s R R 2l
(120) R’ = Et, R2 = R’ = Me, R4 = H

(121) R’ = R4 = Me, R2 = R’ = H
E. J. Corey, J. W. Ponder, and P. Ulrich, Tetrahedron Lerr., 1980, 21, 137.
M. Shibasaki, A Nishida, and S. Ikegami, Teirai7ed:on Letr., 1980, 21, 3061.
139
A. G. Kelly and J . J. Roberts, J. Cheni. Soc., Ciwm. Commun., 1980, 228.
140
S. Ogawa, K . Nakamoto, M. Takahara, Y. Tanno, N. Chida, and T. Suami, Bull. Chem. Soc. Jpn.,
1979,52, 1174.
I41
K. Mori and H. [wasawa, Terrahedron, 1980, 36, 87.
142
Y. Torisawa, M. Shibasaki, and S. Ikegami, Tetmhedrorz Lrti., 1979, 1865.
with dihydropyrans which, on irradiation, give 6,8-dioxabicyclo[3.2.1]0ctanes,'~~

a route to frontalin, starting from the dianion of methyl a ~ e t o a c e t a t eand
, ~ ~the
~
of 2,9-dioxabicyclo[3.3. llnonanes from D-glucose.
Development of synthetic routes to the anthracycline antibiotics is important
because of the cytotoxic properties of many of these compounds. A short route146
to possible intermediates proceeds uia double Diels-Alder addition to (16). The
problem of the availability of (16) has been overcome147by efficient palladium-
catalysed carbomethoxylation of the fur an-maleic anhydride Diels-Alder adduct
to give (122) in 92% yield. Elaboration of Diels-Alder adducts of (16) to
anthracyclines requires rupture of the ether bridge. Acid-catalysed ring-
opening148in simple 7-oxabicyclo[2.2.l]heptaneshas been studied.
(122) E = C02Me
Bridged ethers can readily be prepared by the electrophilic attack of various

organoselenium reagents on olefins. Nicolaou and his group149have given full
details of the attack of selenohalides on unsaturated alcohols (Scheme 21), and
oxyselenation of dienes'" is also effective (Scheme 22). If phenyl selenocyanate
is used in the presence of cupric chloride, as the e l e ~ t r o p h i l e , the
' ~ ~product ratio
(123) : (124) is strongly solvent-dependent. As the organoselenium substituent
6Hhh PhSeCl,
Scheme 21
0- PhSeCl
SePh
( 1 23)
SePh
(124)
Scheme 22
'43 P. Chaquin, B. Furth, and J. Kossanyi, Recl. Trav. Chim. Pays-Bas, 1979, 98, 346.
144 P. E. Sum and L. Weiler, Can. J. Chem., 1979, 57, 1475.
145 H. Redlich, B. Schneider, and W. Francke, Tetrahedron Lett., 1980, 21, 3009, 3013.
146 P-A. Carrupt and P. Vogel, Tetrahedron Leu., 1979, 4533; Y. Bessiere and P. Vogel, Helv. Chirn.
Acta, 1980, 63, 232.
147
C. Mahaim, P-A. Carrupt, J-P. Hagenbuch, A . Florey, and P. Vogel, Heh. Chim. Acta, 1980, 63,
1149.
14' T. A. Eggelte, H. de Koning,'and H. 0. Huisman, Recl. Traa. Chim. Pays-Bas, 1979, 98, 267.
149 K. C. Nicolaou, R. L. Magolda, W. J. Sipio, W. E. Barnette, Z . Lysenko, and M. M. JoulliC, J. Am.
Chem. SOC., 1980,102, 3784.
S. Uemura, A. Toshimitsu, T. Aoai, and M. Okano, Tetrahedron Lett., 1980, 21, 1533.
S. Uemura, A. Toshimitsu, T. Aoai, and M. Okano, J. Chem. Sur., Chem. Cummun., 1980, 610.
Bridged Systems 405
is easily removed,152this metlpd affords a simple entry to either 9-oxabi-

cyclo[4.2.l]nonanes or 9-oxabicyclo[3.3. llnonanes. Electrophilic attack by thal-
lium(rI1) on n e r 0 1 ' ~gives
~ a mixture of bridged ethers and bridged ketals. Buchs
and G a n t e ~ have
l ~ ~ elaborated 9-oxabicyclo[3.3.l]non-6-en-2-oneto further
tricyclic bridged ethers, and the same group have given further examples of the
formation of bridged ethers' 55 by intramolecular nucleophilic addition of alcohols
to alkenes.
Scheme 23
A short synthesis of muscone (125) ( 5 steps; 40% yield) from cyclododeca-

1,5,9-trienelS6involves the key steps shown in Scheme 23.
We also note the formation of (126) by cyclization procedure^'^' with sodium
sulphide, the formation of (127) by closure'5s of a diol, and a reassignment of
to a product of the reaction of 2-methyladamantan-2-01 with
Pb(OAc), and iodine.
An elegant synthesis of oxygen analogues of cocaine16' is shown in Scheme 24.

Further photochemical studies concern the formation of an oxetan in the well-
studied series of 5-acyl-n0rbornenes,~~' and the formation of oxetan from
Is* M. R. Detty, J. Org. Chem., 1980, 45, 274.

15' Y. Yamada, H. Sanjoh, and K. Iguchi, Tetrahedron Lett., 1979, 1323.
154 P. Buchs and C. Ganter, Helv. Chim. Acta, 1980, 63, 970.
lS5 R. A. Pfund, W. B. Schweizer, and C. Ganter, Helv. Chim. Acta, 1980,63,674.
15' K. H. Schulte-Eke, A. Hauser, and G . Ohloff, Helv. Chim. Acta, 1979,62, 2673.
lS7 J. E. Baldwin, M. J. Crossley, and E. M. M. Lehtonen, J. Chem. SOC.,Chem. Commun., 1979,918.
G. W. Erickson and J. L. Fry, J. Org. Chem., 1980, 45, 970.
R. M. Black and G. B. Gill, J. Chem. Soc., Perkin Trans. 1, 1980,410.
16' P. Brownbridge and T-H. Chan, Tetrahedron Lett., 1979,4437.
R. R. Sauers and D . C. Lynch, J. Org. Chem., 1980,45. 1286.
Scheme 24
4-alkoxy-2-quinolones." Irradiationlh3of 3,5-dimethyl-4-pyrone in trifluoro-

ethanol leads to dimers of the type (128) and (129), probably derived from a
zwitterion (130). In furan, the intermediates are intercepted. A new transforma-
(128) (129) (130) (131)
tion of -yS-epoxy-enoneslh4 is shown in Scheme 25, and further details of the

formation of bridged oxa-annulenes in the photolysis of acridine N-oxides16' and
Cope rearrangementlh6of oxepin oxides, e . g . (131), have been reported.
CH2
Scheme 25
Bridged Peroxides.-Routine procedures have been extended to the synthesis

and characterization of photo-adducts of singlet oxygen with cyclo-octa-1,3,5-
triene, 167 cycloheptatrienes,'hX 3,s-cycloheptadienone,169 cyclohepta- 1,3-
dienes,I7' naphthalenes, 1 7 ' a n t h r a c e n e ~ , ~ 'a~- p y r ~ n e s , " ~ pyrazines and
pyrimidine^,'^^ i r n i d a z ~ l e s and
,~~~i n d e n e ~ . ' ~Transformation
' of some of these
162 C. Kaneko, T. Naito, and M. Somei, J. Cher?~. Suc., Chern. Commun., 1979, 804.
163 J. A. Barltrop, A. C. Day, and C. J. Samuel, J. Am. Cham. SOC.,1979, 101, 7521.
B. Frei, H. R. Wolf, and 0. Jeger, Hclv. Chim. Acta, 1979, 6 2 , 1645, 1668.
16' S. Yamada and C. Kaneko, Tetrahedron, 1979, 35, 1273.
Ib6 W. H. Rastetter and T. J. Richard, J. A m . Ch~rn.SOC.,1979, 101, 3893.
'67 W. Adam and I. Erden. Terruhedrori Lptt., 1979, 2781.
lb8 W. Adam, M. Balci, and B. Pietrzak, J. Am. Cheiii. SOC.,1979, 101, 6285; W. Adam and M. Balci.
ibid., p. 7537; M. Yagihara, Y. Kitahara, and T. Asao, Bull. C h e m . SOC.Jpn., 1980, 53, 236.
169 W. Adam and I. Erden, Tetruhedro!i Let[.. 1979, 1975.
I7O D. M. Floyd and C. M. Cimarusti, Teiruhedron [-err., 1979, 4129.
I7l C. J. M. van deli Heuvel, H. Steinberg, and T. J. de Boer, R e d . Trav. Chirn. Pays-Bus, 1980,99,109.
I72
J. Rigaudy, A. Defoin, and J. Baranne-Lafont, Angew. Chem., Int. Ed. Engl., 1979, 18, 413.
17' W. Adam and I. Erden, J. A m . Chem. SOC..1979, 101, 5692.
174 J. L. Markham and P. G. Sammes, J. Chrin. Soc., Perkin Trans. 1, 1979, 1885.
175 H-S. Ryang and C. S. Footc, J. Am. CIwm. Snc., 1979, 101, 6683.
J. D. Boyd and C. S. Foote. J. A m . Chem. Soc., 1979, 101, 6758.
Bridged Systems 407
endoperoxide adducts to polyepoxides has been reviewed,s and is the subject of

further reports. '77 Isomerization of peroxides from cycloheptatrienes affords a
convenient synthesis of homobenzoquinones.'71 Photolysis of ascaridole at
185 nm leads, in part, to loss of oxygen by c y c l o r e v e r ~ i o n ,in
~ ~contrast
~ to
thermolysis or low-energy photolysis, which lead to isoascaridole.
Interest in the prostaglandin endoperoxides continues to serve as a focus for
synthetic studies. The formation of bicyclic peroxides by halide displacement
from a monocyclic hydroperoxide proceeds180in moderate yield. A full paper
reports"' on an alternative procedure whereby a monocyclic diol can be closed,
again in moderate yield, to a bicyclic peroxide by reaction with bisjtri-n-butyltin)
peroxide.
We also note studies concerning effects of magnetic fields on the kinetics18*of
decomposition of endoperoxides, solvent effect^''^ on the decomposition of
peroxides, and the acid-catalysed decomposition of ozonides. 84
6 Systems containing Sulphur

Synthesis by Cyc1oaddition.-Further details have been given of high-pressure
Diels-Alder a d d i t i ~ n ' ~of
' maleic anhydride to thiophen, and we note the
formafionls6 of Diels-Alder adducts from 2H-thiopyran, of the dimer (132),18'
and of the adduct (133).ls8
Miscellaneous Syntheses and Reactions.-The reaction of thiirans with chlorine

can provide a useful method1s9of synthesis of bridged thioethers (Scheme 26).
We also note the synthesis of 8-thiabicyclo[3.2.1]octan-3-one,19nthe isolation of
177 W. Adam and M. Balci, J. A m . Chem. Soc., 1979, 101, 7542; J. D. Boyd, C. S. Foote, and D. K.
Imagawa, ibid., 1980, 102, 3641; W. Adam and M. Balci, ibid., p. 1961.
'71 W. Adam, M. Balci, and J. Rivera, Synthesis, 1979, 807.
R. Srinivasan, K. H. Brown, J. A. Ors, L. S. White, and W. Adam, J. Am. Chem. Soc., 1979, 101,
7424.
A. J. Bloodworth and H. J. Eggelte, J. Chem. SOC.,Chem. Commun., 1979, 741; A. J. Bloodworth
and H. J. Eggelte, Tetrahedrou Letf., 1980, 21, 2001.
M. F. Salomon and R. G. Salomon, J. Am. Chem. SOC.,1979,101,4290.
N. J. Turro and M.-F. Chow, J. A m . Chem. SOC., 1979, 101, 3701.
D. J. Coughlin and R. G. Salomon, J. A m . Chem. SOC.,1979, 101, 2761.
lS4 M. Miura and M. Nojima, J. Chem. SOC., Chem. Commun., 1979, 467.
H. Kotsuki, H. Nishizawa, S. Kitagawa, M. Ochi, N. Yamasaki, K. Matsuoka, and T. Tokoroyama,
Bull. Chem. SOC. Jpn., 1979, 52, 544.
R. H. Fleming and B. M. Murray, J. Org. Chem., 1979, 44, 2280.
M. Behforouz and R. Benrashid, Tetrahedron Lett., 1979, 4493.
"* J. Dalling, J. H. Gall, and D. D. MacNicol, Tetrahedron Lett., 1979, 4789.
P. H. McCabe and A. Stewart, J. Chem. Soc., Chem. Commun., 1980, 100.
T. Sasaki, S. Eguchi. and T. Hioki, hhterocycles, 1979, 13, 293.
b s
S c1
CJ
cl&clS S LCI
Scheme 26
the bridged sulphide (134) from peppermint and the determination of the
rate of h y d r ~ l y s i sof
' ~ the
~ strained vinyl sulphide (135) and related compounds.
t 134) (135)
7 Systems containing Other Heteroatoms

The first stable bridged germanium compounds have been reported. Addition'93
of benzyne to the germole (136) gives (137) in good yield. Addition'94 of KSeCN
to dienes provides an alternative to the addition of selenium halide that leads to
bridged selenides.
Russian interest in the synthesis of bridged boranes is considerable, and
synthetic studies concern the cyclization of triallylborane with 1 , l -dimethyl-
allene'95 to give (138), which is readily transformed into 4,4-dimethyl-l-bora-
adamantane. Other alkyl- 1-bora-adamantanes l Y 6have been prepared and their
antiviral activities r e p ~ r t e d , ' ~ '
T. Yoshida, S. Muraki, K. Takahashi, T. Kato, C. Kabuto, T. Suzuki, T. Uyehara, and T. Ohnuma,

J. Chem. SOC.,Chem. Comrnun., 1979,512.
W. K. Chwang, A. J. Kresge, and J. R. Wiseman, J. A m . Chem. SOC.,1979, 101, 6972.
W. P. Neumann and M. Schriewer, Tetrahedron Lett., 1980, 21, 3073.
lY4 A. Toshimitsu, S. Uemura, and M. Okano, J. Chem. SOC.,Perkin Trans. I , 1979, 1206.
B. M. Mikhailov, V. N. Smirnov, 0. D. Smirnova, E. P. Prokof'ev, and A. S. Shashkov, Izv. A k a d .
Nauk SSSR, Ser. Khim., 1979,2340.
196 B. M. Mikhailov, T. V. Potapova, and A. S. Shashkov, Izv. A k a d . Nauk SSSR, Ser. Khim., 1979,
2724.
197 B. M. Mikhailov, V. N. Zmirnov, 0. D. Smirnov, V. A. Kasparov, N. A. Lagutkin, N. I. Mitin, and
M. M. Zubairov, Khim. Farm. Zh., 1979, 13,3 5 .

Bridged Systems 409
Me, ,Me
Me Me Ph
The highlight of synthetic studies with bridged phosphorus compounds

concerns additions19*to (139). Cyclobutadiene gives an adduct, readily photo-
isomerized to (140). Addition199 of diethyl azodicarboxylate to (141) gives
the quinquevalent phosphorus derivative (142), which is readily transformed
into (143). Gas-phase proton affinities have been reported2" for (141) and
related cyclic phosphites.
R R
(139) R = CF3 (140) R = CF,
EtO
\
Y. Kobayashi, H. Hamana, S. Fujino, A. Ohsawa, and I. Kumadaki, J. Org. Chem., 1979,44,4930.

199 J. Navech, R. Kraemer, and J. P. Majoral, Tetrahedron Lett., 1980, 21, 1449.
R. V. Hodges, F. A. Houle, J. L. Beauchamp, R. A. Montag, and J. G. Verkade, J. Am. Chem.
SOC.,1980,102, 932.
Author Index
Abagyan, E. L., 292 Ahrnad, Z. S., 32 Alves de Lima, R., 307, 314
Abbott, S. D., 229 Ahrned, I., 212 Arnano, K., 262
Abdallah, M., 390 Ahnfelt-R~nne,I., 94 Arnato, J. S., 126, 282
Abdallah, M. M., 114 Ahuja, A. S., 128 Arnbekar, S. Y., 160, 173
Abd Allah, S. O., 119 Aiello, E., 343 Amble, E., 364
Abd Elmawgoud, I. A., 114 Airnetti, J. A,, 57 Arnbrosio, M., 171, 323
Abdel Fadel, H., 196 Airno, G., 186 Ambrossini, A,, 300
Abdel-Megeid, F. M. E., 318 Akabori, S., 369 Arnbrus, G., 110
Abdulla, R. F., 53, 224 Akasaka, T., 31 Arnbrus, I. P., 20
Abdul-Malik, N. F., 316 Akiba, K., 123, 124, 136 Ames, A., 78
Abe, N., 205 Akirnoto, I., 149 Amey, R. L., 193
Abe, Y., 210 Akirnoto, T., 209 Arnin, S. G., 5 5
Abignente, E., 125 Akirnova, T. I., 19 Amrnon, H. L., 347
Abis, L., 279 Akita, M., 269 Amosova, S. V., 75, 280
Abood, N., 230 Akita, Y., 261 Amzil, J . , 169
Abou-Gharbia, M. A., 29, 5 5 , Akiyama, T., 261 Anand, N., 314, 335
117, 192 Akopyan, A. N., 88, 286 Anani, A. A., 199
Abraham, W.-R., 92, 305 Akopyan, R. A,, 102 Anapolle, K. E., 389
Abrarnova, A. M., 330 Akopyan, T. R., 368 Anastasia, M., 13
Abrarnenko, P. I., 86 Aksanova, L. A., 153 Anastassiou, A. G., 360, 398
Abrarnovitch, R. A., 223, 233 Akulin, Y. I., 141 Anchisi, C . , 202
Abyshev, A. Z . , 326 Alagona, G. 15 Ander, I., 77, 103
Achenbach, H., 148 Alange, G. G., 145 Anderegg, G., 364
Acheson, R. M., 105, 146, Albanesi, S., 38, 189, 362 Anderegg, J . H., 68
167, 183, 231, 243, 333, Albaugh, P., 63 Anderson, C. D., 336, 340
388 Alberghina, G. 87 Anderson, M. D., 261
Achirnov, D. L., 231 Albert, A,, 267, 269, 271 Anderson, P. N., 336
Acker, K . J . , 317 Alberts, A. H., 374 Anderson, P. S., 247, 393
Ackermann, J . , 330 Albini, A., 353 Anderson, V. B., 386
Ackrell, J . , 342 Albrecht, D., 142 Anderson, W. K., 8
Adachi, H., 288 Albrecht, H. A., 281 Ando, H., 295
Adachi, J . , 134, 135, 138, 140 Albro, P. W., 153 Andreichikov, Y. S., 321
Adachi, M., 343 Alcalde, E., 208 Andriarnizaka, J. D., 72
Adam, K. R., 364 Alder, R. W., 385, 392, 397 Andrianov, V. G., 209
Adam, W., 2, 63, 67, 68, 150, Alekseev, N. N., 99, 104, 314 Andriyankova, L. V., 275
287, 381, 399, 406, 407 Alekseev, N. V., 383 Andronati, S. A., 224, 345
Adarns, M. A., 284 Aleksandrov, G. G., 169, 319 Anet, F. A. L., 14
Adarnsone, B. Ya., 180 Alexandrou, N. E., 194 Anfilogova, S. N., 152
Adesogan, E. K., 308 Alexanian, V.. 38 Angle, S., 191
Adiwidjaja, G., 60, 114, 135, Al-Holly, M. M., 114 Angelini, G., 158
186 Ali, M. E., 306 Angelova, I., 325
Advani, G. G., 11 1 Ali, M. I., 133 Anisimov, A. V., 84
Aftalion, H. 20 Ali, S. A., 188 Annunziata, R., 8
Aftandilians, N., 195 Ali, Sk. A., 335 Ansari, H . R., 8
Agashkin, 0. V., 114 Ali, S. M., 27 Ansell, J. M., 289
Agawa, T., 205 Alieva, F. M., 3 Anselrni, C., 283
Agbalyan, S. G., 88 Allen, D. W., 92 Anthoni, U., 167
Aggarwal, N., 8 3 Allgren, R. L., 399 Antipin, M. Yu., 79
Agosta, W. G., 24 Alrnadi, G., 43 Antonova, A., 105, 146
Agustin, M., 157 Alonso, J. L., 322 Antus, S., 297
Ahern, M. F., 251 Alper, H., 41 Anzeveno, P. B., 37, 216, 328
Ahlberg, P., 370 Al-Sharnma, A., 328 Aoai, T., 348, 404
Ahluwalia, V. K., 312, 325 Alta, F. M., 5 5 Aoki, N., 171
Ahmad, I., 6 Altenbach, H. J . , 360 Aoyarna, H., 54, 55, 59
Ahmad, M., 168 Alvernhe, G., 35 Aoyama, S., 147
411
412 A u thor Index
Appel, R., 29 Auterhoff, H., 163 Ban, C., 137

Aradis, F., 130 Avakyan, T. T., 6 Ban, T., 383
Arai, H., 209, 217 Avendano, C., 386 Ban, Y., 58, 161, 241, 245,
Arai, S., 136 Aversa, M. C., 345 334
Arai, Y., 8, 135, 206 Avetisyan, A. A., 312 Bando, T., 239
Arakawa, S., 24 Avots, A. A,, 223 Banerji, A,, 299, 314
Arakelyan, R. H., 110 Avramovici-Grisaru, S., 230 Banerji, J., 314, 390
Arbuzov, B. A., 14, 329, 330, Awad, S. B., 316 Banerji, K. D., 96
350 Awaji, H., 173 Bank, S., 385
Arcoria, A., 103 Ayi, A. I., 87 Banister, A. J., 145
Ardabilchi, N., 191 Ayral-Kaloustian, S., 24 Baradarani, M. M., 233
Ardakani, M., 180 Ayyangar, N. R., 333 Baranne-Lafont, J., 406
Arena, F.. 125 Azerbaev, I. N., 118 Barascut, J. L., 224
Arends, P., 319 Barboiu, V., 196, 207
Ariga, M., 213, 396 Bard, R. R., 161
Arison, B. H., 10 Babaitsev, V. S., 8 4 Barillier, D., 105, 170
Armarego, W. L. F., 223, 272 Babcock, R. W., 285 Barker, J. M., 74
Arnaud, M., 289 Babichev, F. S., 213 Barkley, R. M., 269
Arnold, D. R., 60, 178 Babsch, H., 331 Barlow, M. G., 226, 230, 387,
Arnold, E. V., 286 Bach, R. D., 4 389
Arnold, P., 116 Bachelet, J.-P., 98 Barltrop, J . A., 406
Arnold, R. J., 123 Bachi, M. D., 56, 59 Barluenga, J., 226, 239, 253,
Arnoldi, A., 122 Bacon, C. C., 70 260
Arnone, C., 79 Bacon, R. G. R., 237 Barner, R., 294
Arnost, M. J., 291 Badanyan, S. O., 292 Barnes, A. C., 318
Arora, P. K., 297 Baddawy, H., 196 Barnes, J. F., 199
Arrigoni-Martelli, E., 94 Baddeley, G. V., 16 Barnette, W. E., 404
Arrowsmith, R. J., 392 Badri, R., 360 Barney, C., 238
Artico, M., 335 Baggs, M. E. M., 396 Barnish, I. T., 125
Artyukhin, V. I., 118 Bahadir, M., 135 Barone, R., 180
Arvanaghi, M., 27 Bahadur, G. A,, 166 Barr, J . J., 57
Arventiev, B., 119 Baiker, A., 2 Barraclough, P., 334
Arya, V. P., 133 Bailey, A. S., 166, 206, 212 Barrans, J., 202
Asakawa, H., 88, 322 Bailey, T. R., 2 Barrett, A. G. M., 360
Asami, M., 193 Bairov, V. V., 280 Barrio, J. R., 268
Asano, T., 270 Bajgrowicz, J. A , , 223 Barrow, M. J . , 199
Asao, T., 155, 257, 406 Bak, B., 72, 135 Barta, I., 110
Asato, G., 8 9 Bak, C., 184 Barrels, G., 128
Ashcroft, P. L., 199 Baker, J . T., 160 Bartha, B., 18
Ashe, A. J., 330 Baker, R. J., 140 Bartholomew, D., 181, 260
Asherson, J. L., 244 Baker, S. R., 226, 287 Bartkowiak, F., 9
Ashida, T., 118 Bakker, B. H., 391 Bartl, A., 61
Ashour, F. A., 357 Bakker, C. G., 148 Bartlett, P. A., 382
Ashcraf, C. M., 6 Bako, E. M., 198 Bartlett, P. D., 51
Asinger, F., 116, 117 Bal, M. S., 133 Bartnik, R., 37
Askani, R., 399 Balasubrahmanyam, S. N., Bartok, M., 63, 322
Asmus, K.-D., 385 199 Barton, D. H. R., 360
Asprou, C. M., 96 Balavoine, G., 231 Barton, J. W., 103, 214, 223
Assmann, F., 55, 115 Balbi, A., 300 Bartsch, R. A., 369, 370
Atal, C. K., 314, 326 Balci, M., 381, 399, 406, 407 Baruah, N. C., 306
Atkins, T. J., 363 Baldry, P. A., 206 Barve, M. V., 313
Atkinson, J. G., 164, 281, 288 Baldwin, J . E., 148, 405 B a d e , M., 117
Atkinson, R. S., 28 Baldwin, J . J., 10, 162, 226 Basina, N. I., 288
Atsumi, K., 151 Baldwin, S. W., 395 Bass, R. G., 127
Attanasi, O., 122 Balenkova, E. S., 152 Bass, R. J., 309
Attar, A., 314 Balenovic, K., 288 Basse, W., 112
Attia, M., 37 Balicki, R., 214 Bastien, G., 91
Atwood, J. L., 159, 160, 398 Ballantine, J. A., 167 Basyouni, M. N., 171
Au, M.-K., 362 Ballentine, N. H., 314 Bates, R. B., 20, 154, 225
Aubagnac, J. L., 121 Ballard, H. H., 97 Batich, C., 384
Audisio, G., 157 Ballesteros, P., 386 Bats, J. W., 367
Augustin, M., 99, 114, 120 Balode, D., 107, 185 Battistini, C., 63
Auksi, H., 320 Bal’on, Ya, G., 110 Battistoni, P., 122
Aurousseau, M., 98 Balsamo, A,, 63 Batzer, H., 66
A u thor Index 413
Baudy, M., 111 Berestovitskaya, V. M., 91 Blanton, C. D. jun., 150

Baukov, Y. A., 65 Berg, C., 72, 135 Blarzino, C., 119
Baukov, Y. I., 69 Berg, U., 112 Blazevie, N., 224
Bauman, L. E., 51 Berge, D. D., 19, 303, 304 Bleisch, S., 61
Baurnstark, A. L., 67 Bergernon, R. T., 260 Blenderman, W. G., 90
Bayyuk, S. I., 390, 391 Bergman, J., 69, 113, 154 Block, E., 71
Baxter, A. J. G., 56 Bergrnann, F., 267 Bloodworth, A. J., 407
Baxter, S. L., 368 Bergstrom, R. G., 168 Blount, J. R., 165, 281, 341
Bazbouz, A., 169 Berk, H. C., 197 Bludssus, W., 140, 276
Bazzi, A. A., 71 Bernardi, R., 346 Bluhm, T., 195
Beard, C. C., 136 Bernasconi, S., 290 Boberg, F., 170
Bearden, W. H., 385 Bernhard, E., 155 Bock, H., 173
Beatie, J. E., 134 Bernstein, J., 8 8 Bode, B., 277
Beauchamp, J. L., 409 Berson, J. A., 399 Bodrikov, I. V., 41
Beaulieu, N., 152 Berti, G., 283 Boehme, H., 131, 194, 265,
Beaumont, D., 250 Bertie, J. E., 44 352
Beavers, W. A., 20, 154 Bertolassi, V., 129 Boehrne, R., 71
Becher, J., 234 Bertrand, M., 17 Boehnisch, V. W., 121, 280
Bechgaard, K., 173 Bessiere, Y., 404 Boekelheide, V., 52, 249
Beck, G., 253 Bester, M., 180 Boshagen, H., 95, 107, 108
Becker, H.-D., 347 Bestmann, H. J., 71, 194 Boev, V. I., 290
Beeken, P., 235, 238 Betaneli, L. V., 388 Bogan, D, J., 68
Beelitz, K., 84, 303 Betterton, K., 370 Bogat-skii, A. V., 224, 345,
Beer, R. J. S., 116, 142 Bettinetti, G. E., 263, 353 349, 368
Begasse, B., 298 Beugelmans, R., 161, 162 Bogdanov, V. S., 4 3 , 4 4
Beger, J., 110 Beyer, L., 118, 282 Bognor, R., 105
Begtrup, M., 111 Bhaduri, A. P., 224 Bogomolova, G. S., 169
Behera, R. K., 117 Bhakta, C., 310 Bohlmann, F., 92, 305, 308,
Behforouz, M., 100, 407 Bhandori, K., 335 315
Behjati, B., 195 Bhanumati, S., 326 Bohman, O., 370
Behr, H., 60, 114 Bhaskar, V., 257 Boido, A,, 264
Beier, B., 285 Bhat, K., 325 Boigegrain, R., 87
Beierbeck, H., 96 Bhat, V., 33, 146, 192, 197, Boisdon, M. T., 202
Bekemeier, H., 306 224 Bokadia, M. M., 19, 303
Bekker, R. A., 65 Bhattacharjee, S. K., 383 Boldeskul, I. E., 201
Belanger, P., 158 Bhide, B. H., 315 Bollaert, W., 101
Belen’kii, L. I., 78, 80 Bhide, G. V., 9 3 Bolouri, A. M. A,, 390
Beletskaya, I. P., 119 Bianchi, G., 146 Bombala, M. U., 42
Belikova, G. S., 183 Bianchi, M., 358 Bondavalli, F., 386
Belin, B., 224 Bickelhaupt, F., 360 Bondi, E., 180
Bell, B., 145 Bicker, U., 34 Bonetta, A., 323
Bell, H. C., 8 3 Bielka, S., 99 Bonetti, M., 364
Bell, L. M., 60 Bienick, D., 314 Bonfiglio, J. N., 235
Belletire, J. L., 313 Bierangel, H., 183 Bongini, A., 296
Belli, A., 279 Biernat, J., 127 Bonini, B. F., 234
Bellinger, O., 90 Bigg, D. C., 118 Bonjoch, J., 382
Bellmann, P., 106 Biglino, G., 324 Bonsall, E., 218, 342
Bellus, D., 1 3 Bigot, B., 33, 47 Bonsignone, L., 322
Bellville, D. J., 330 Bihlmaier, W., 173 Boonyarakvanich, A., 390
Belostotskaya, I. S., 201 Bilgic, S., 334 Borchers, F., 32
Belov, P. N., 30 Binder, D., 86, 99 Borda, J., 309
Beltrami, H., 233 Bird, C. W., 276 Borisevich, A. N., 142
Belzecki, C., 60 Bird, T. G. C., 298 Borisova, L. N., 86
Berni, L., 339 Birkner, EL, 305 Bornstein, J., 389
Benati, L., 163 Bistocchi, G. A., 299, 347 Borodavko, N. D., 118
Benedikt, J., 203 Biswas, K., 319 Borodina, L. N., 298
Ben-Ishai, D., 246 Biswas, K. M., 306 Borror, A. L., 108
Bennett, G. B., 19 Bizzozero, N., 217 Boruah, R. C., 190
Bennett, P., 305 Bjerre, C., 72, 135, 204 Boscacci, A. B., 47, 53
Beno, M. A., 14 Black, D. St. C., 47, 52, 53, Bosch, J., 382
Benrashid, R., 100, 407 159 Bose, A. K., 55
Bentley, P. M., 355 Black, L. J., 98 Bosies, E., 34
Benton, W. H., 368 Black, R. M., 405 Bosse, D., 180
Benz, W., 345 Blackrnan, N. A,, 47, 53, 159 Bostock, S. B., 153
414 Author Index
Botteghi, C., 75 Brookhart, T., 152 Burkholder, W. E., 289

Bottino, F., 367 Brooks, G., 355 Burns, P. A., 67
Bouchet, P., 176 Brooks, W. V. F., 14 Burzlaff, H., 71
Bouffard, F. A,, 56 Brotherton, C. E., 261 Busby, R. E., 243, 254
Boujlel, K., 367 Brovchenko, 0. P., 329 Buser, H. R., 153, 323
Boukou-Poba, J . P., 156 Brown, C., 305 Bushby, R. J., 42, 178
Bouley, E., 243 Brown, D. E., 389 Buss, V., 189
Boulton, A. J., 146, 199 Brown, F. C., 104 Butler, A. R., 49, 182, 207
Bouillant, M. L., 308 Brown, H. C., 22, 321, 384 Butler, R. N., 181, 208
Bouma, W. J., 15 Brown, H. S., 367 Bykanova, N. V., 218
Bourelle-Wargnier, F., 346 Brown, J. R., 322
Bourguignon, J., 103 Brown, K. H., 238, 407 Caca, M. P., 172
Bovee, W. M. M. J., 384 Brown, L., 400 Cadelli, G., 307
Bovill, M. J., 376 Brown, R. F. C., 52, 159 Caine, D., 148
Bower, D. J., 239, 390 Brown, R. S . , 231 Calo, V., 10, 122
Bowlus, S. B., 96 Brown, S. A., 283 Cambell, H. F., 386
Box, V. G. S., 296 Brownbridge, P., 405 Cambie, R. C., 114
Boyd, D. B., 58 Browne, A. R., 196 Cameron, T. B., 42, 186
Boyd, D. R., 11, 48 Brownlee, R. T. C., 290 Cameron, T. S., 212
Boyd, J. D., 406, 407 Briickner, R., 218, 358 Camoutis, Ch., 223
Boyer, J. H., 198 Bruggermann, K., 236 Campaigne, E., 97, 131
Boykin, D. W., 76 Bruentrup, G., 64 Campbell, D. H., 3
Boykin, D. W., jun, 76 Brugger, E., 162 Campbell, M. M., 360
Bradac, J., 66 Bruice, T. C., 11 Campbell, W. E., 315
Bradmante, S., 69 Brune, G., 31 Campion, P., 121
Bradshaw, 368, 378 Brunskill, J . S. A., 96 Camps, F., 296
Bradsher, C. K., 390 Bruzik, K., 330 Camps, P., 180
Brahler, G., 173 Bryant, J. D., 258 Canada, L. G., 160
Bramm, E., 94 Bubel, 0. N., 298 Cantisani, A., 308
Bramwell, F. B., 77 Bubnov, N. N., 201 Capellini, C., 290
Brandes, W., 117 Buchanan, G. W., 32 Capozzi, G., 44
Brandsma, L., 83 Buchardt, O., 167, 234 Capuano, L., 61, 140, 200,
Brandt, E. V., 327 Buchholz, G., 84, 303 270
Brannegan, D. P., 287 Buchs, P., 405 Caputi, A. P., 125
Bratt, J., 102, 230 Buchwalter, S. L., 399 Caputo, O., 292, 324
Braverman, S., 327 Buck, H. M., 81, 112, 210, Carballeira, N., 399
Bravo, P., 147, 303, 346 384 Cardillo, G., 296
Brazier, J. F., 200 Buczkowska, D., 215 Cardllina, J. H . jun., 286
Brederick, H., 265 Budarin, L. I., 379 Carey, J. Y . , 356
Breitenbach, R., 287 Budeanu, C. H., 130 Carganico, G., 174
Breitmaier, E., 110, 217, 228 Budhram, R. S., 213 Carless, H. A. J., 62
Breivik, H., 128 Budic, B., 66 Carlock, J. T., 29, 348
Bren, V. A., 97 Budny, J., 36 Carola, M., 125
Brennan, T. M., 287 Buhl, H., 76, 134 Carreira, L. A,, 51
Bresciani-Pahor, N., 367 Buendia, J., 66 Carrit, R., 30, 195
Breuer, E., 71 Buerkle, W., 10, 32 Carroll, G. L., 401
Breugst, I., 301 Bui Cong Chanh, 202 Carrupt, P. A., 384, 404
Breuker, K., 254 Bukachuk, 0. M., 81 Cartoon, M. E. K., 391
Breuninger, M., 360 Bulka, E., 119 Carulla, J. M., 98
Breviglieri, G., 112 Bullock, E., 333, 396 Caruso, F., 190, 273
Bridson, P. K., 268 Bundy, G. L., 402 Cashen, M. J., 168
Briehl, H., 190 Buncel, E., 199 Casson, A., 397
Brien, D. J., 398 Bunk, E., 133 Castells, J., 113
Brieskorn, C. H., 308 Bunnett, J. F., 161 Castle, R. N., 79, 214
Briggs, A. G . , 109, 205 Burakevich, J. A., 224 Catalano, S., 15, 218, 335
Brine, D. R., 296 Burchardt, B., 16, 346 Catelani, G., 283
Brinkmeyer, R. S., 224 Burden, R. S., 305 Catoni, G., 79
Brion, J. D., 293 Burgada, R., 200 Catsoulacos, P., 223
Britcher, S. F., 247, 393 Burger, K., 56, 61, 144, 174, Cattel, L., 292, 324
Brittain, J. M., 77 181, 262 Caujolle, R., 386
Brokatzky, J., 25 Burger, U., 210 Cauquis, G., 207
Bronder, M., 270 Burke, B. A., 296, 315 Cava, M. P., 172
Brook, A. G. 72 Burkert, U., 322 Cavagna, F., 7, 58
Brooke, G. M., 388 Burkhart, G., 225 Cavier, R., 98
Author Index 415
Cawkill, E., 137 Chida, N., 403 Closs, G. L., 399
Ceccherelli, P., 303 Chidichimo, G., 31 Coates, R. M., 205
Cere, V., 291 Chiericato, M., 174 Coccia, R., 119
Cerefice, S. A., 3 Child, R. G., 27 Cognion, J. M., 3
Cernayovh, M., 84 Chirnirri, A., 118 Cogolli, P., 78, 149
Cerri, R., 264 Chisaka, A., 151, 366 Cohen, L. A., 221
Cervinka, O., 361 Chiu, S.-K., 140 Cohen, M. L., 240, 398
Cetina, R. R., 3 Cho, B. R., 369 Conen-Fernandes, P., 176
Chabannet, M., 288 Cholpankulova, S. T., 114, Cohenour, P. T., 12
Chacko, E., 389 118 Colberg, H., 234, 332
Chacko, K. K., 383 Chopin, J., 308 Cole, R. J., 3 11
Chadha, V. K., 133 Chou, T.-S., 388 Coll, J., 296
Chadwick, D. J., 157, 376 Chow, M.-F., 407 Coller, B. A. W., 87
Chae, W. R., 399 Chow, S.-Y., 133 Collignon, N., 262
Chakraborty, P. K., 98 Chow, Y. L., 198, 395 Colnago, L. A., 164
Challis, B. C., 49 Chowdhury, S. A., 306 Colon, I., 70
Chambers, R. D., 252, 264 Christensen, A. T., 217 Colonna, M., 168
Chamot, E., 196 Christensen, B. G., 56, 57 Colton, C. D., 247, 393
Champagne, P. J., 87 Christensen, J. J., 234, 368, Coman, M., 112
Chan, E. Y., 354 378 Comber, R. N., 255
Chan, T.-H., 405 Christian, G. D., 331 Compton, D. A. C., 72
Chan, T. L., 318, 362 Christiansen, J. J., 143 Conalty, M. L., 297
Chandrachood, P. S., 354 Christie, R. M., 205 Condom, R., 87
Chandrakumar, N. S., 88 Christl, B., 171 Confalone, D. L., 312
Chandrasurin, P. 77 Christl, M., 331 Confalone, P. N., 312
Chang, H. W., 56 Christoph, G. G., 14 Consiglio, G., 79
Chang, K.-C., 176 Christopherson, C., 167, 204 Constantini, M., 8
Chang, K. T., 46, 316 Christy, M. E., 247, 393 Cook, C. E., 314
Chang, S. F., 307 Chu, C. K., 256 Cook, L. S., 265
Chang, V. H. T., 356 Chu, T.-P., 172 Cooke, R. G., 317
Chang, Y.-H., 72 Chuaqui-Offermanns, N., 199 Cookson, R. F., 223
Chanon, M., 112 Chuche, J., 346 Coppa, F., 283
Chao, Y., 372, 373 Chun, M.-W., 208 Copeland, C., 168
Chapleo, C. B., 27 Chung, W. K., 256 Coppola, G. M., 163, 242
Chapput, A., 77 Chunin, E. D., 193 Corbella, A., 290
Chaquin, P., 404 Churkin, Yu. D., 79 Corda, L., 202
Charbonnel, Y., 202 Chwang, W. K., 408 Cordes, R. E., 212
Charner, J., 36 Ciesiolka, J., 127 Cordt, F., 138
Charrier, J., 53 Ciganek, E., 168 Corey, E. J., 8, 232, 403
Charumilind, P., 186 Cimarusti, C. M., 56, 406 Cormons, A., 283
Chatterjea, J. N., 310 Cincotta, L., 108 Corno, M. L., 307
Chatterjee, A., 112, 314 Cini, C., 119 Corwin, L. R., 399
Chattopadhyay, G., 110, 127 Cinquini, M., 192 Cosmao, J.-M., 262
Chaudhary, S. K., 153 Ciocoiu, I., 130 Cossy, J., 160
Chavis, C., 224 Cirrincione, G., 343 Costa, D. L. B., 304
Cheeseman, G. W. H., 212, Citerio, L., 161, 181, 195, Coste, J., 169
223, 391 265 Costello, G., 166
Chen, C. C., 293 Ciuciu, M., 123 Costescu, R., 20
Chen, C. H., 286, 291, 292 Ciurdaru, G., 123 Coughlin, D. J., 407
Chen, H.-H., 133 Claesson, A., 147, 157, 283 Council, S. L., 192
Chen, T.-K., 390 Clapp, L., 354 Couquelet, J., 302
Chen, T.-S., 396 Claramunt, R. M., 208 Couret, C., 72
Chenard, 8 . L., 96 Clardy, J., 170, 286, 289, 306 Courtot-Coupez, J., 99
Cheng, C.-C., 67 Clark, D. A., 232 Couturier, D., 17
Cheng, D. M., 268 Clark, G., 176 Covington, R. R., 132
Cherkasov, R. A., 200 Clark, P. D., 96 Cowan, D. O., 77
Chern, J. W., 133 Clark, R., 8 Cowell, A., 148
Chervin, I. I., 30 Clarke, K., 73, 96, 107, 356 Cox, R. H., 311
Cheung, H. T. A,, 16 Claus, K., 279 Cozzi, F., 192
Chhabra, S. C., 326 Clausen, K., 86 Crabb, T. A., 361
Chiang, Y., 168 Clayton, J. P., 74 Cragg, G. M. L., 315
Chiba, K., 58, 241 Clement, A,, 44, 134, 170 Craig, D., 319
Chiba, T., 64, 122, 211 Cleveland, W. K. S., 385 Craig, N. C., 47
Chibber, S. S., 310 Cliffe, I. A., 157 Cram, D. J., 372, 373, 374
416 Author Index
Crampton, R. G., 354 Dash, B. C . , 116 Demmin, ’I. R., 348

Crans, D. C., 401 Dash, M., 110 Denis, J. N., 21
Crawford, R. J., 179 Date, T., 53 Denninger, G., 202
Cristol, H., 169 Datta, S. K., 132 Dennis, N., 390, 391
Crombie, D. A., 291 Dattolo, G., 343 Depeshko, I. T., 112
Crombie, L., 226, 252, 287, Dauplaise, D., 170 Derguini-Roumechal, F., 21,
328 D’Auria, M., 150 62
Cromwell, N. H., 32, 51 Daves, G. D., jun., 166 Dert, V., 91, 324
Crosby, G. A,, 7 David, G., 150 Deru, N., 82
Crosby, J., 144, 199 Davidson, A., 130 Dervan, P. B., 160
Cross, P. E., 125 Davies, D. I., 146 Deryagina, E. N., 85
Crossland, N. M., 27 Davies, J., 292 Desai, J. A., 111, 130
Crossley, M. J., 148, 405 Davis, A. L., 190 Deschamps-Vallet, C., 304
Crotti, P., 63 Davis, F. A,, 48, 51 Deshayes, C., 288
Crow, W. D., 154 Davis, J. H., 399 Deshpande, D. S., 129
Crozet, M. P., 91 Davis, M. A., 135 Desirnoni, G., 167, 177
Cruzzola, G., 307 Davis, P. D., 165 Deslongchamps, P., 152
Cueto, O., 67, 68 Davis, R., 385 Dettwiler, H. R., 2
Cugnon de Sevricourt, M., 92, Davis, R. C., 107 Detty, M. R., 25, 405
343 Day, A. C., 406 Devaquet, A,, 33, 47
Cum, G., 31 De, A., 96 Devillanova, F. A., 112
Cupano, J., 120 Deady, L. W., 112, 212 Dewick, P. M., 304
Curini, M., 303 De Bie, M. J. A., 320 Dhaka, K. S., 133
Curphey, M. E., 393 de Boer, T. J., 406 Dhar, D. N., 66
Curran, W. V., 301 De Caprariis, P., 125 Dhar, K. L., 309, 314, 326
Curtze, J., 210 Declercq, J . P., 43, 70, 116, Diaconescu, D., 137
Cusmano, G., 198 135, 145, 345 Di Braccio, M., 300
Cuthbertson, A. F., 136 De Clercq, P. J., 402 Dickinson, K. H., 56
Cutler, A. T., 391 De Dalal, I., 98 Dickinson, R. P., 125
Cuvigny, T., 334 de Hann, J . W., 384 Didry, J. R., 314
Cyr, T. D., 289 De Jong, F., 367 Dietzsch, T., 157
Czarny, A., 217 de Koning, H., 404 Dijkstra, D., 94
Czuba, W., 223 Del Campo, C. S., 314 Dike, S., 310
Czyzewski, J., 109, 205 del Giudice, M. R., 345 Dimofte, P., 20
Delle Monache, F., 304, 309, Dimroth, K., 329
Dach, R., 210 314 Dimroth, P., 225
Da Col, L., 44 Delle Monache, G., 307, 309 Dimsdale, M. J., 245
Dagley, T. J., 317 De Lucchi, O., 68, 399 Dingwall, J., 175, 337
Dahl, W. E., 123 De Marco, C., 119 Di Ninno, F., 57, 190
Dahlen, B., 186 De Maria, P., 112 Di Nunno, L., 190
Dahlmann, J., 13 De Mayo, P., 71, 241 Dittmer, D. C., 51, 70
Dahmen, F. J. M., 148 de Meijere, A., 399 Dixit, V. M., 192, 197
Daidone, G., 343 De Mello, J. F., 309 Djokar, K., 270
Dakternieks, D., 71 De Meo, G., 299, 347 Dlabat, A,, 96
D’Albuquerque, I. L., 304 De Micheli, C., 146 Dmitrienko, G. I., 165
Dale, J., 364 De Vries, J. G., 371 Dmitrieva, N. D., 329
Dalla Croce, P., 174, 182 de Weck, G., 349 Do, M. T., 33
Dalling, J., 407 De Wit, A. D., 52 Doddi, G., 158, 290
D’Aloiso, R. D., 251 Deeva, N. Yu., 120 Doehner, R. E., 400
Dalzell, H. C., 294 Defoin, A., 406 Doelling, K., 111
D’Amico, J. J., 123 Degani, I., 186 Dopp, D., 162, 167
Damon, M. C., 283 Degen, H . J., 215 Doering, F., 253
Damon, R. E., 163 Dehrnlow, E. V., 166, 369 Dohmori, R., 132
Damrauer, R., 361 Dehne, H., 184 Dolan, 392
Dandarovh, M., 84 Dehnel, R. B., 6 Dolbier, W. R., 389
Dangyan, M. T., 312 Dekerk, J. P., 43, 70, 116 Doll, R . J., 395
Daniels, P. H., 160 Delaunay, J., 285 Dolton, C. D., 393
Daniels, R., 175 Deligeorgiev, T., 120 Dombrovskii, A. V., 290
Danilina, N. I., 345 Delmas, M., 321 Dominh, T., 28
Danilkina, L. P., 72 Delpech, B., 394 Dommisse, R. A., 286
Dao, K. H., 386 Demarne, H., 345 Dornschke, G., 61, 148
Dao, Le, H., 196 Demersernan, P., 98 Donahue, K., 313
da Rocha, J. F., 223 Demian, H., 112 DoNascimento, E. A., 277
Das, G., 17 Demina, L. A,, 187 Donati, D., 188
Author Index 417
Dondoni, A., 129, 290 Ebata, T., 57 El-Sohly, H. N., 305

Donnelly, D., 300 Ebbinghaus, C. F., 278 El’tsov, A. V., 99, 111
Donnelly, J. A,, 303, 305 Eberbach, W., 16, 25, 346 Emsley, J., 42
Donskova, A. I., 14 Ebert, R. W., 28 Encarnacion, L. A. A., 63
Doria, G., 307 Eby, S., 361 Enda, J., 205
Dorn, H., 179 Echter, T., 135 Endo, J., 17
Dorner, J . W., 311 Eckhardt, H . H., 274 Engel, P. S., 381, 399
Dorofeenko, G. N., 155, 283, Eckhardt, K . , 326 Englehardt, E L., 247, 393
288 Eckstein, Z . , 320 Enkaku, M., 101, 102, 248,
Dortmund, D., 126, 282 Ecob, C. M., 153 338, 339
Doughty, D. G.. 214 Edasery, J. P., 32 Epishina, L. V., 386
Douglas, A. W., 45, 160 Edo, K., 230, 254 Erastov, 0. A., 329, 330, 350
Doukas, P. H., 29 Edoho, E. J., 160 Erbea, R., 279
Doushak, L. N., 294 Edward, J. T., 386 Erchak, N. P., 83
Dove, R. V., 226, 287 Edwards, J. M., 306 Erden, I . , 2, 67, 287, 399,
Dowlatshahi, H., 391 Edwards, 0. E., 386 406
Dowlatshahi, H. A., 391 Edwards, W. B., 53 Erdtman, H., 153
Dowle, M. D., 146 Efros, L. S., 141, 283 Eremeev, A. V., 34, 40, 209,
Dragota, I., 298 Egawa, H., 213 260
Drankenberg, T., 104 Ege, G., 116, 208, 227, 266 Zremenko, 0. N., 170
Drapier, J., 191 Egestad, B., 154 Eres’ko, V. A., 386
Drechsler, H . J., 131, 194, Eggelte, H. J., 150, 360, 407 Erickson, G. W., 405
265 Eggelte, T. A., 404 Erkelens, C., 176
Dreier, F., 210 Eggersdorfer, M., 262 Ermili, A., 300
Driscoll, J. S., 342 Eghtessad, E., 136, 198 Ermishov, A, Yu., 123
Drobnik, J., 313 Egorochkin, A. N., 196 Ershov, V. V., 201
Droste, H., 321 Eguchi, S., 301, 395, 407 Esafov, V. I., 88
Drozd, V. N., 70, 121, 169, Ehlers, J., 44, 56, 134, 135 Esayan, G. E., 110
171 Ehlinger, E., 62 Eschenmoser, A., 33, 364
Druganov, A. G., 181 Eicher, T., 211 Escudie, J., 72
Druzhinina, G. I., 118 Eiden, F., 96, 288, 301, 350 Esmans, E. L., 286
Dube, S., 286 Eilazyan, 0. G., 214 Espada, M., 384
Dubey, A. K., 225 Eilingsfeld, H., 100, 125 Essassi, E. M., 358
Duchardt, K. H., 210 Eisner, U., 261, 331 Essawy, A,, 114.
Duckett, J. A., 63 Ekstrom, A., 364 Estes, V. M., 15
Dudek, V., 361 El-Abadelah, M. M., 31, 199 Eudy, N. H., 94, 355
Duggan, A. J., 284 Elbahaii, S. A., 119 Eugster, C. H., 149, 313, 317,
Dulcere, J. P., 17 Elbarbary, A. A., 318 402
Dulenko, V. I., 288, 314 Elben, U., 368 Evans, B. E., 247, 393
Dumm, H. V., 202 El-Brembaly, K. M., 125, 139 Evans, S. A., 320
Dumont, 224 El’chaninov, M. M., 92 Eweiss, N. F., 138
Dunach, E., 113 Eldawy, M. A., 125, 139 Ewing, D. F., 96
Dunand, A,, 267 Elder, J. W., 386 Ezaki, A., 62
Duncan, C. D., 178, 399 Elder, R. C., 400
Dunston, B. T., 52 El Faghi, M. E. A., 96
Durand, R., 97 Elguero, J., 121, 125, 174, Fabio, P. F., 27
Durant, J. L., 68 176, 180, 207, 208, 365 Fabre-Bonvin, J., 308
Durgaryan, A. A., 110 Eliel, E. L., 322 Fabrichnyi, B. P., 89
Durig, J. R., 72 Elison, J., 390. Fadda, A. M., 322
Durst, T., 1, 186 El Khashef, H . , 92 Fagan, P. J., 177
Dust, J . M., 386 El-Kholy, I . El. S., 288 Fahmy, A. F., 114
Dusza, J. P., 110 El’kinson, R. S., 40, 260 Fahmy, A. F. M., 196, 273
Dutasta, J. P., 200 Ellencweig, A., 323 Fahr, E., 196
Dyall, L. K., 194 Elling, W., 384 Fainzilberg, A. A., 187
Dyumaev, K. M., 244 Elliot, S., 248 Fales, H . M., 147
Dzhemilev, U. M., 4 Elliott, M. L., 287 Falou, S., 285
Dzhumaev, I. A., 104 Ellis, E. W., 108 Falstone, G., 286
Dzurilla, M., 60 Ellis, G. P., 287, 300, 305 Fanghanel, E., 172, 277
Ellis, P. S., 198 Fanshawe, W. J., 165
Elmobayed, M., 114 Farachi, C., 157
Earl, R. A., 317 Elmore, N. F., 105 Faragher, R., 235, 273
Easton, J. W., 96 El Namaky, H. M., 170 Farinas, S., 149
Easton, N. R. jun., 14 Eloy, F., 89, 386 Farkas, E. R., 57, 105
Eaton, D. F., 257 Elrod, D. W., 323 Farklas, L., 18
418 Author Index
Farnier, M., 156 Fletcher, I. J., 391 Frost, J. R., 191, 301
Fasani, E., 263 Flitsch, W., 221, 397 Frost, J. W., 48
Fatma, W., 305 Florencio, F., 383 Fruchier, A,, 176
Fauduet, H., 200 Florey, A., 404 Fry, J. L., 21, 405
Faulkner, D. J., 289 Florio, S., 190 Fu, P. P., 11, 12
Faull, A. W., 122, 193 Flowers, W. T., 138, 191 Fuchigami, T., 136, 197
FaurC, R., 114, 121, 125, 171, Floyd, D. M., 21, 406 Fuchita, T., 21
323 Fochi, R., 186 Fuchs, B., 323
Faust, J., 114 Foehlisch, B., 70, 402 Fuchs, H. B., 368
Fava, A., 291 Foerster, W. R., 135 Fuess, H., 367
Fava, G., 122 Fokin, A. V., 41, 330 Fuhlhuber, H. D., 399
Federsel, H. J., 69, 113 Foley, J. W., 108 Fujii, T., 268
Fedorova, N. S., 99, 111 Fomum, Z. T., 181 Fujikane, K., 137
Fedoseev, V. M., 169 Foote, C. S., 66, 182, 406, Fujimori, K., 131
Fedynyshyn, T. H., 343 407 Fujimoto, Y., 4
Fehlauer, A., 175 Forbes Cameron, A., 360 Fujino, S., 409
Felcht, U.-H., 7 Forgione, A., 307 Fujita, R., 386
Felix, D., 33 Forlani, L., 112, 121, 129 Fujitani, T., 295
Felman, S. W., 22 Fornarini, S., 290 Fujito, H., 74
Fenech, G., 117, 118 Forni, A., 47 Fujiwara, Y., 148
Fengeas, C., 323 Forrester, A. R., 249 Fukada, N., 109
Ferguson, G., 345 Forsyth, D. A., 76, 77 Fukai, T., 306
Ferik, S., 208 Fortunato, J. M., 218, 343 Fukatsu, S., 226
Feron, A., 191 Foster, N. G., 77 Fukumi, H., 186
Ferrand, G., 125, 132 Foster, R. H., 268 Fukumoto, K., 55, 205, 359
Ferrari, M., 290 Foti, F., 190, 273 Fukunaga, K., 187
Ferraudi, G. J., 33 Foti, S., 367 Fukushima, T., 69, 324
Ferreira, P. C., 307 Foucaud, A., 36, 53, 111 Fukushima, Y., 322
Ferretti, M., 15 Fowler, F. W., 235, 238 Fukutani, Y., 137
Ferruti, P., 157 Fox, J. J., 256 Fukuyama, K., 137
Feugeas, C., 171 Fox, M. J., 303, 305 Fuller, L. S., 73
Fiandanese, V., 10 Fox, W. R., 73 Funaki, K., 57
Fiaschi, R., 218, 335 Foye, W. O., 230 Fung, A. P., 362
Ficarra, P., 345 Franck, R. W., 216 Fung, L. W. M., 66
Ficerra, P., 117 Francke, W., 404 Furth, B., 404
Fichtner, M. W., 170 Franck-Neumann, M., 138 Furukawa, H., 211
Ficini, J., 285 Frank, A., 267 Furukawa, M., 56
Fiecchi, A., 13 Frank, M. E., 8 Furukawa, N., 31
Fields, E. K., 3 Frank, R. M., 138 Furukawa, Y., 135, 272
Fields, R., 194 Franke, H., 200 Fuse, M., 148.
Filliatre, C., 285 Franke, K., 166 Fushimi, T., 334
Filyakova, T. I., 13 Franz, J. E., 197 Fuss, A., 179
Findeisen, K., 265 Frappier, F., 35 Fustero, S., 226, 253.
Finer, J. S., 289 Freeman, J. P., 176
Finkelstein, J. A., 246 Freeman, W. J., 341
Finlay, J. D., 69, 186, 385 Frei, B., 23, 349, 406 Gaabe, H., 351
Finlayson, W. L., 112 Freijee, F. J. M., 382 Gabel, R. A., 229
Finsen, L., 234 Frejd, T., 81, 82, 103 Gackwad, Y. G., 300
Fiorenza, M., 188 Frenna, V., 198 Gad, F. A., 318
Firl, J., 56, 61, 144, 174, 181 Frensch, K., 368 Gadsby, B., 125
Fischer, G. W., 232, 390, 391 Frey, H. M., 285 Gaetani, E., 107
Fischer, H., 175, 203 Frey, 0. H . , 227 Gagneux, A. R., 398
Fisera, L., 173, 209 Fridh, C., 14 Gal, D., 6
Fisichella, S., 87 Friedman, H. S., 330 Gale, D. J., 296
Fitton, A. O., 191, 301, 354 Friedrich, K., 134 Galeazzi, E., 342
Flament, I., 261 Frimer, A. A., 51 Galkin, V. I., 200
Flammang, R., 32 Fristad, W. E., 2, 14 Gall, J. H., 164, 295, 407
Fleischhauer, J., 169 Fritz, H., 25 Gall, R., 34
Flekhter, B. V., 91 Fritz, U . , 308 Gallagher, P. T., 146, 224
Flemal, J., 145 Frobese, A. S., 148 Gallagher, T. C., 194
Fleming, I., 161 Frohberger, P. E., 117 Galle, R., 112
Fleming, R. H., 407 Frolov, E. B., 152 Gallenkamp. B., 360
Fleming, S., 273 Frolow, F., 327 Galli, C., 79
Flesia, E., 91 Fronza, G., 69, 346 Galli, P., 122
Author Index 419
Gallo, R., 112 Geurtsen, G., 27 1 Goebel, A. M., 190

Galloway, N., 155 Gewald, K., 85, 106, 110, Gopfert, H., 285
Galvez, E., 384 242, 251 Goerdeler, J., 136
Galy, J. P., 125 Ghali, E. A., 171 Gorlitzer, K., 95
Gambaryan, N. P., 60, 191, Ghori, M., 291 Goetze, R., 77
280 Ghosai, S., 319 Goetzschel, K., 111
Gambino, J., 255 Ghosez, L., 227 Goghari, M. H., 162
Gammill, R. B., 301, 302 Ghoss, C., 302 Gogte, V. N., 41
Gandha, B., 84 Gia, O., 325 Gohda, N., 121
Gandhi, C. S., 128 Giam, C.-S., 229, 236 Gohke, K., 294
Gandolfi, R., 146 Giancaspro, C., 158 Gokan, K., 261
Ganem, B., 5 Giannetto, P., 345 Gokel, G. W., 186, 251, 370
Ganguly, R. N., 398 Gibert, J. P., 209 Golankiewicz, B., 269
Ganter, C., 405 Giesecke, H., 115 Goldberg, O., 59
Gal, T. K., 383 Gil, G., 17 Gol’dfarb, Ya. L., 78, 80, 89,
Garanti, L., 216, 217, 265, Gilbert, K., 208, 266 97, 104
337, 338 Gilchrist, T. L., 102, 121, Golfier, M., 200
Garcia-Blanco, S., 383 184, 235, 245, 273, 280, Golic, L., 111
Gardner, J. O., 136 356 Golobolov, Yu. G., 201
Garg, C. P., 300 Giles, R. G., 24 Golser, W., 270
Garg, S. K., 315 Gilis, P. M., 101 Golubeva, G. A., 162
Gariboldi, P., 290 Gill, G. B., 405 Golubok, Y. G., 18
Garito, A. F., 172 Gill, M., 249 Golyak. V. M., 314
Garland, J. T., 150 Gillard, M., 227 Gomi, M., 234
Garland, W. A., 348 Gillespie, R. J., 87 Gompper, R., 123, 183, 227,
Garner, T. B., 320 Gillissen, H., 384 263, 387
Garratt, P. J., 74, 147 Gilman, H., 83 Gonbeau, D., 210
Garrigues, B., 200, 202 Gilmore, C. J., 164 Goncharenko, F. V., 98
Gaset, A., 321 Gilow, H. M., 158 Gonda, K., 259
Gashimov, N. F., 326 Gilpin, M. L., 355 Gonsho, A., 207
Gates, M., 343 Ginak, A. I., 18, 118, 123 Gontar, S. S., 118
Gatta, F., 345 Ginsburg, D., 381, 390 Goode, R. L., 98
Gattuso, M. I., 123 Ginsburg, H., 162 Goodland, M. C., 214
Gautam, S., 207 Ginsti, G., 323 Goodwin, T. E., 229
Gauthier, M. M., 32 Gioia, B., 181, 189, 362 Goomer, N. C., 299
Gavrilova, G. M., 280 Giordano, C., 278 Goosen, A., 168
Gavrilova, Z. A., 379 Giordano, L., 125 Gorb, L. T., 128, 133
Geetha, P., 18, 87 Girard, Y., 106, 164, 277, Gorban, I. Ya., 330
Geiger, W., 95, 107, 108 281, 288 Gordon, B. G., tert., 20, 154,
Geigo, F., 113 Giraud, J., 98 2.25
Gein, L. F., 321 Girotra, N. N., 231 Gordon, E. M., 56
Gein, V. L., 321 Gisby, G. P., 388 Gordon, P. F., 184
Geissner-Prettre, C., 268 Gitterman, A., 91 Gorelik, M. V., 179
Geittner, J., 173 Giusti, G., 171 Gorindan, S. V., 306
Gelas-Mialhe, Y., 37 Givia, B., 265 Gornicki, P., 127
Gelin, S., 251, 288 Glacet, C., 117 Gorrichon, J. P., 321
Gel’mont, M. M., 141 Glamkowski, E. J., 218, 343 Gorvin, J. H., 249
Geneste, P., 96, 97 Glaspy, P. E., 156 Goswami, N. K., 141
Gentric, E., 112 Glaze, A. P., 45 Goto, T., 67
George, M. V., 33, 146, 192, Glazer, R. D., 55 Gotoh, H., 137
197, 224 Gleadhill, B., 107, 356 Gotor, V., 226, 253
Geoges, F., 361 Gleason, J. G., 51 Gotthardt, H., 61, 69, 111,
Gerasimenko, Yu. E., 329 Gleiter, R., 381 171, 197, 327
Geraskov, B. I., 164 Glennon, R. A., 127 Gottlieb, H. E., 314
Gerdes, H. M., 186 Glennow, C., 80 Gottlieb, 0. R., 283
Gerecht, B., 190 Glick, M. D., 367 Gottsegen, A., 297
Gergely, A., 297 Glidewell, C., 136 Gottstein, W., 70, 402
Gerisch, K., 357 Glode, J., 200 Gougoutas, J. Z., 56
Gerloff, J., 258 Gloia, B., 38 Gould, K. J., 214
Germain, G., 43, 70, 116, Glover, E. E., 214 Gousetis, C., 399
135, 145, 345 Gluzinski, P., 287 Govorek, V. K., 84
Germane, S. K., 83 Gobi, M., 385. Grabley, F. F., 71
Gershanova, E. L., 5 Gockel, U., 387 Grabley, S., 40
Gesing, E. R., 221, 397 Godefroi, E. F., 81 Grabowski, Z. R., 47
420 A uthor Index
Griifing, R., 83 Gunther, D., 180 Hall, C. R., 69, 385

Graffe, B., 295 Guerchais, J. E., 83 Hallberg, A., 80, 81, 82, 103
Gralak, J., 7 Guest, A. W., 74 Haller, S., 215
Grand, A,, 200 Guglielmetti, R., 115 Hallett, P., 23
Grandi, R., 173 Guha, S. K., 96 Halton, B., 155
Granville Shaw, C. J., 243, Guibe, F., 231 Hamada, H., 245, 409
254 Guilard, R., 156 Hamana, M., 245
Grasshoff, H., 200 Guimaraes, A. C . , 200 Hamanaka, K., 187
Grassi, G., 190, 273 Guiotto, A., 325 Hamashima, Y., 57
Grasso, S., 118 Gujral, V. K., 304, 308 Hamed, A., 196
Craw, S., 135 Gulasekharam, V., 350 Hamel, P., 106, 277
Gray, G. A., 32 Gunatilaka, A . A. L., 317 Hamelin, J . , 179
Graziano, M. L., 182 Gunda, T. E., 5.7, 105 Hamerlinck, J. H. H., 210
Greci, L., 168, 212 Gunning, H. E., 44, 170 Hamersma, J. A. M., 118
Green, B. S., 88 Gupta, G. K., 326 Hamilton, J. G., 11
Green, D. C., 146 Gupta, P. K., 55 Hamilton, R., 48
Green, I. R., 24 Gupta, R. B., 297 Hammouda, H. A . , 133
Green, L., 94 Gupta, R. C., 324, 325 Hamprecht, G., 282
Greenhouse, R., 154 Gupta, R. R., 141 Hamuro, Y., 88
Greffen, D., 279 Gupta, S. R., 304, 308, 315, Han, H.-T., 5
Greger, H., 315 326 Hanafusa, T., 354
Gregory, B., 333, 396 Gupta, V. K., 133 Hanaki, A., 13, 295
Grehn, L., 126, 157 Gupta, V. P., 315 Hanaoka, M., 36
Greuter, H., 13 Gurkova, S. N., 383 Hanaya, K., 294
Grezzo, L. A ., 384 Guryn, R., 345 Handrick, G. R., 294
Grierson, D. S., 238 Gusarov, A. N., 92 Hanefeld, W., 117
Griffiths, D. W., 42 Gusev, A. I., 383 Hanifin. J. W., 88
Grigorev, I. A,, 181, 183 Gustafsson, K., 347 Hankovsky, 0. H., 363
Grigoryan, G. V., 88 Gutbrod, H.-D., 349 Hanley, R. N., 144, 204
Griller, D., 209, 385 Gybin, A. S., 43, 44 Hannoun, M., 96
Grimaldi, J., 283 Hanocq, M., 141
Grimmett, M. R., 176 Hansen, B., 192, 204
Grimminger, W., 2 Haag, J., 136 Hansen, H., 281
Grindley, T. B., 350 Haas, T., 328 Hansen, H. C., 144
Grinev, A . N., 86 Habison, G., 99 Hansen, H. J., 109, 195
Grinter, T. J., 107 Habraken, C. L., 176 Hansen, J., 205
Grisebach, H., 283 Hacker, N. P., 255 Hansen, J. F., 176, 177
Griswold, L. J . , 176 Haddadin, M. J., 176 Hansen, J. J . , 188
Grob, C. A., 386 Haddon, R. C., 77 Hanson, R. N., 135, 393
Groh, R., 157 Hadi, A. H. b. A., 191 Hantke, K., 110, 180
Grohe, K., 117 Haekli, H., 46 Hantschmann, A., 143
Grol, C. J., 94 Hausermann, E., 358 Hanzawa, Y., 61, 349
Gronowitz, S., 77, 78, 79, 80, Hafmers, A., 101 Hara, M., 79
81, 82, 84, 103, 104, 266 Hagaman, E. W., 130 Hara, S., 149
Gross, A., 59 Hagan, J . P., 291 Harada, M., 15
Gross, H., 200 Hagenbuch, J.-P., 404 Haralda, H., 314
Gross, M. L., 32 Haggag, B., 95, 170 Harano, K., 217, 383
Grossi, A. V., 193 Haghgooii, H., 292 Harborne, J. B., 283
Groth, P., 383 Hagiwara, H., 148, 217, 349 Harding, M. M., 199
Groth, U., 261 Hagmann, W. K., 156, 251 Hardtmann, G. E., 242
Grove, J . F., 311 Hahn, C. S., 158 Hardy, A. D. U., 295, 302
Grover, P. K., 314 Haiduc, I., 104 Hariri, M., 270
Grudzinski, Z., 402 Haire, M. J., 393 Harkema, S., 52, 350
Gruendemann, E., 34, 179 Hairsine, P. W., 318 Harnisch, J., 52
Grugel, C., 47 Hajdu, I. P., 6 Harrington, G. W., 259
Grund, H., 189 Hajek, M., 147 Harris, D., 218
Gruntz, U., 290 Hajos, G., 215 Harris, M., 238
Gruzdev, N. V., 298 Hakushi, T., 67 Harris, T. M., 317
Grynkiewicz, G., 287 Halat, M. J . , 256 Harris, W. C. 71
Gubar. V. I., 314 Halevi, E. A., 178 Harrison, E. A., 243, 347
Gubernator, K., 160, 395 Haley, B. F., 77 Harrison, E. A., jun., 101,
Guedj, R., 41, 87 Haley, M. J., 138 168
Guendel, W.-H., 232 Haley, N. F., 170 Harrit, N., 113, 192, 204
Guenthard, H. H., 176 Halfar, W., 288 Hart, D. J., 243
Author Index 42 1
Hart, H., 389 Hercouet, A , , 147, 152, 283, Hoffmann, W., 75

Harten, L. A., 88 297, 298 Hofmann, A. A., 149,402
Hartless, R. L., 28, 33 Herin, M., 26 Hofmann, C. M., 75
Hartman, A., 250 Hermecz, I., 270 Hofmann, H., 351
Hartman, R. D., 226 Herndon, W. C., 51, 398 Hofmeister, P., 72, 330
Hartmann, H., 142, 143, 224 Herrnstadt, C., 345 Hohner, G., 381
Hartmann, W., 168 Herslof, M., 78, 82 Hojo, M., 112, 278
Hartmannsgruber, U., 387 Hertenstein, U., 64 Holden, H. D., 136
Hartwig, W., 261 Herz, W., 306 Holden, I., 328
Harutunian, V., 213 Heshino, M., 69 Holla, B. S., 160, 173
Harvey, R. G., 11, 12 Heublein, A., 179 Hollander, R. C., 180
Hasan, I., 235 Heuck, U., 157 Hollins, R. A . , 164
Hasegawa, J., 370 Hewgill, F. R., 218, 347 Hollinsed, W. C., 384
Hasegawa, K., 262 Hewitt, D. G., 218, 347 Holm, A., 72, 113, 135, 143,
Hasegawa, T., 54, 55 Hewitt, L. E., 312 192,204
Haselgrave, J. A., 378 Heydt, A., 134, 191 Holmes, A . B., 383
Hashiba, M., 353 Heydt, H., 124 Holmes, B. N., 269
Hashimoto, M., 55 Heywood, V. H., 283 Holmes, N. H., 142
Hashizume, T., 334 Hiatt, R. R., 361 Holst, H., 311
Hassan, K. M., 55 Hibino, S., 147, 234 Holt, G., 191
Hassan, M. E. R., 107 Hida, M., 62 Holtschmidt, H., 253
Hassaneen, H. M., 138 Hideg, K., 130, 363 Holtwick, J. B., 269
Hassner, A., 38, 289, 394 Hideg-Hankovszky, O., 130 Holubek, J., 92
Haszeldine, R. N., 226, 230, Hiermann, A., 304 Holubka, J. W., 4
387, 389 Higashino, T., 224 Homfeld, E., 97
Hata, Y., 28, 48, 276 Higgins, R. W., 77 Homma, H., 128
Hausen, B., 113 Highet, R. J., 147 Hones, J. H., 191
Hauser, A., 405 Higuchi, T., 319 Hongo, H., 386
Hauser, H. J., 213 Hiiragi, M., 55 Hoogwater, D. A., 155
Hawkins, D. G., 87 Hill, E. A., 398 Hopf, H., 402
Hayashi, E., 224 Hill, J. A., 154 Hoppe, D., 5 5
Hayashi, H., 139 Hillebrand, F., 86 Hordvik, A , , 116
Hayashi, N., 35 Hiller, K.-O., 385 Hori, M., 124, 277, 319, 353
Hayashi, S., 306, 327 Hiltunen, L., 210 Hori, T., 5
Hayashi, S. I., 188 Himling, H., 234 Horie, H., 43
Hayes, D. M., 348 Hino, T., 207 Horie, T., 306, 327
Hayward, R. C., 374 Hinz, W., 117 Horiguchi, Y., 332
Heck, R. F., 242 Hinze, R. P., 128 Horino, H., 241, 311
Heckendorn, R., 258 Hioki, T., 407 Horn, U., 33
Hedstrand, D. M., 237 Hirai, K., 53, 94, 129, 344 Horng. J.-M., 229
Heeg, K., 215 Hirai, S., 95 Hornykiewytsch, T., 399
Heerdt, R., 34 Hirai, Y., 53, 359 Horstmann, H., 139
Hegel, R. F., 132 Hirako, N., 131 Horvath, G., 110
Heggs, R. P., 5 Hiraoka, T., 56 Horvath, K., 198
Heidrich, R., 351 Hirata, K., 365 Hoshi, N., 349
Heikes, J. E., 135 Hiroi, K., 352 Hoshino, M., 324
Heilbronner, E., 384 Hirokami, S., 53., 359 Hosoki, A., 140
Heilmann, S. M., 320 Hirose, T., 342 Hotta, K., 153
Heimgartner, H., 38, 40 Hirota, K., 256, 257 Houalla, D., 200, 210
Hein, F., 56, 174, 181 Hirotsu, K., 306 Houghton, P. G., 203,301,354
Heine, H. G., 168 Hirsch, B., 142 Houghton, R. A., 393
Heine, H. W., 45, 218, 342 Hisano, T., 217 Houle, F. A,, 409
Heinemann, W., 227 Hitomi, H., 24 Houser, D. J., 188, 323
Heinisch, G., 252 Hlasta, D. J., 53 Howden, M. E. H., 239,390
Helgeson, R. C., 373, 374 Hoberg, H., 225 Howie, G. B., 218, 347
Henderson, W. A,, 126 Hocker, J., 115 Hoyer, E., 170
Hendriks, H. M. J., 183 Hodges, R. V., 409 Hrusovsky, I., 203
Henkel, U., 173 Hodgkinson, L. C., 375 Hsu, K. K., 307
Henneke, K. W., 191 Hoegberg, H. E., 153 Huang, B.-S., 269
Henning, H. G., 157 Hoelle, G. W., 176 Huang, C.-T.. 5
Henrick, K., 364 Hopfner, U., 234, 332 Hubert, A. J., 191
Henricks, P. M., 291 Hornfeldt, A.-B., 79, 104 Huckerley, T. N., 301
Henriksen, L., 180 Hofeditz, W., 160, 395 Huddleston, P. R., 74
Herbert, R. B., 224 Hoffman, P., 260 Hudson, P. B., 328
Author Index
Huffman, J. C., 131 Ioannisci, M., 182 Ito, Y., 68, 161, 342
Hufford, C. D., 305, 306 Ionescu, M., 20 Itoh, M., 12, 135, 250
Hufnal, J. M., 186 Ionin, B. I., 19.7 Itokawa, H., 17
Huisgen, R., 60, 173, 174, 178 Ionova, V. F., 84 Iulian, M., 20
Huisman, H. O., 404 Iovanov, I., 112 Ivanov, K., 325
Hull, R., 193, 122, 220 Ipach, I., 164 Ivanova, Zh. M., 201
Hullot, P., 334 Ippen, J., 172 Ivkina, A. A., 248
Hungerbuehler, E., 1 0 Iqbal, J., 305 Iwai, I., 74
Hunt, E., 355 Iqbal, M., 243 Iwaki, T., 288
Hunt, J. H., 146 Irnafuku, K., 215 Iwama, M., 261
Husbands, M. J., 122 Imagawa, D. X., 407 Iwamoto, K., 120
Huss, 0. M., 171 Imai, T., 6 3 Iwamura, H., 14
Hussain, I., 182 Imai, Y., 124 Iwano, Y., 5 3
Hussain, S. A., 209 Imaizumi, S., 294 Iwao, M., 212
Hussain, S. M., 243 Imamiya, E., 88, 322 Iwasa, A., 21
Husson, H.-P., 238 Imanishi, T., 36 Iwasawa, H., 403
Hutchins, C. W., 205 Imbach, J. L., 224 Iwasawa, N., 150
Hutchins, R. O., 22, 382 Imberlin, F., 33 Izatt, R. M., 368, 378
Hutley, B. G., 9 2 Imoto, E., 33 Izumi, T., 342
Huttner, G., 329 Imuns, V. A., 40, 260
Hutton, J., 192 Imuta, M., 14, 26
Hutzenlaub, W., 268 Inaba, S., 342 Jackson, B., 109
Huybrechts, L., 7 0 Inada, A., 40 Jackson, B. D., 96
Huynh, C., 2 1 , 6 2 Inagaki, Y., 142 Jackson, G. C., 361
Huys, F., 180 Inamoto, M., 124 Jacobsen, J. P., 205
Hwang, D., 274 Inamoto, N., 123, 142 Jacobsen, N. W., 256
Hwang, F.-Y., 229 Inanaga, J., 365 Jacobsen, R. M., 239
Inbasekaran, M., 263, 271 Jacobson, R. A., 220
Ingham, J. L., 304 Jacobson, S. E., 5
Iaccobucci, G. A., 307 Ingle, D. B., 110 Jacquier, R., 176
Ibrahim, A. El Sabai, 126 Ingold, K. U., 204, 285, 385 Jaeger, V., 189
Ichiba, M., 267 Inomata, K., 147 Jaehnisch, K., 34
Ichikawa, K., 15, 18 Inoue, H., 33, 62 Jagtap, R. S., 146
Ichikawa, M., 217 Inoue, I., 268 Jahreis, G., 120
Ichikawa, N., 326 Inoue, M., 15, 18 Jain, A. C., 296, 307, 324,
Ichikawa, S., 131 Inoue, N., 241, 311 325
Ida, Y., 217 Inoue, S., 25, 287 Jain, P. C., 335
Iddon, B., 102, 146, 224, 230 Inoue, Y., 67 Jain, S. K., 141
Ide, J., 7 4 Inouye, Y., 370 Jaisli, F., 364
Ide, Y., 57 Inukai, Y., 120, 152 Jakobsen, P., 280
Iesce, M. R., 182 Ireland, C., 289 Janak, K., 138
Igeta, H., 209, 210, 217 Ireland, R. E., 284 Janda, M., 76
Ignatenko, A. G., 214 Irie, H . , 242, 334 Jankowski, K., 314
Ignatev, V. M., 193 Ishiba, T., 94, 129, 344 Janousek, Z., 180
Ignatov, V. F., 92, 122 Ishida, H., 35 Janse, A. C. V., 91, 324
Iguchi, K., 405 Ishihara, R., 370 Jansen, M., 399
Iguchi, M., 17 Ishii, Y., 20 Janssen, C. G. M., 8 1
Ihara, M., 29, 165, 205, 359 Ishikawa, N., 120 Jaques, B., 212
Iifura, M., 252 Ishikura, K . , 57 Jarczewski, A., 369
Iijima, K., 171 Ishimori, M., 10 Jarosz, S., 6 3
Iijima, T., 4 3 Ishitoku, T., 5 9 Jarrar, A. A., 31
Iinuma, M., 306 Ishizumi, K., 342 Jarreau, F.-X., 35
Iitaka, Y., 13, 166, 209, 295 Ishratullah, K., 305 Jaszberenyi, C., 105
Ikeda, K., 262 Ismail, H., 305 Jaszberenyi, J . C., 57
Ikeda, M., 139, 208, 319 Isobe, K., 35, 148, 230, 322 Jawdosiuk, M., 8
Ikeda, T., 5 Isomura, Y., 128 Jaworski, T., 192
Ikegami, S., 403 Istomina, Z. I., 28, 37 Jay, M., 308
Ikemi-Kono, Y., 231, 388 Itagaki, Y., 319 Jayne, G. J. J., 42
Ikemori, S., 148 Itaka, Y., 17, 332 Jedlinski, Z . , 66
Ikuta, H., 334 Itaya, T., 268 Jeffrey, H., 9 6
Il’in, G. F., 77 Iten, P. X., 149, 402 Jeger, O., 23, 349,406
Mi, V. O., 164 Ito, M. M., 195, 227 Jenkins, J. A., 400
Illuminati, G., 79, 158, 290 Ito, N., 128 Jenkins, R., 48
Ilotse, J. B., 304 Ito, S., 20, 266, 269 Jennings, R. C., 7, 297
Author Index 423
Jennings-White, C. L. D., 383 Kai, Y., 383 Kartashova, T. A., 86

Jente, R., 9 2 Kaiser, R., 402 Karunayake, S., 319
Jentsch, R., 42, 278 Kajfei, F., 96, 224, 344, 345 Kasai, E., 370
Jerina, D. M., 1 2 Kaji, A., 238 Kasai, M., 3 11
Jewell, L. M., 322 Kajitani, M., 370 Kasai, N., 383
Jilek, J., 96 Kakehi, A., 266 Kashiwagi, T., 61, 349
Jiricny, J., 268 Kakisawa, H., 188, 242 Kaskar, B., 66
Jirkovsky, I., 325 Kakiuchi, H., 43 Kasparov, V. A., 408
Joers, J., 15 Kakudo, M., 118 Kasprzyk, S. P., 345
Jogdeo, P. S., 9 3 Kalabin, G. A., 75, 280 Kassab, N. A., 119
Johansen, 0. H., 88, 302, Kalal, J., 313 Kasturi, T. R., 249
328, 383 Kalasinsky, V. F., 7 1 Kasuga, K., 366
Johansson, E. M., 249 Kale, A. V., 304 Katagiri, N., 64, 240, 317
John, D. I., 57 Kalik, M. A., 78 Kataoka, T., 95, 124, 277,
Johnson, B. D., 8 8 Kalikhman, I. D., 110, 321 319,353
Johnson, C. R., 8, 30, 7 0 Kalinin, A. E., 169 Katayarna, I., 242
Johnson, J. L., 323 Kalinin, A. I., 196 Kato, H., 151, 171, 386
Johnson, M. R., 375,376 Kalman, J. R., 8 3 Kato, K., 155
Johnson-Streusand, M., 72 Kaloustian, M. K., 321 Kato, T., 64, 122, 157, 211,
Johnston, D. B. R., 56 Kal’yan, Yu. B., 4 3 240, 317, 408
Johnstone, L. M., 47 Kam, B. L., 227 Katrenko, Yu. S., 345
Jokisaari, J., 6 3 Kamalov, G. L., 349 Katritzky, A. R., 146, 224,
Jokl, J., 313 Kamdar, B. V., 253, 345 232, 233, 290, 390, 391
Jommi, G., 290 Kamela, Z., 273 Katsube, Y., 137
Joncheray, G., 176 Kamernitskii, A. V., 28 Katsuki, T., 365
Jonczyk, A., 8 Karnetani, T., 29, 55, 165, Katsura, M., 208
Jones, D. S., 224 205, 359 Katsuragawa, B., 287
Jones, G., 102, 213 Karninskii, V. A., 294 Kauffman, J. M., 230
Jones, G., see., 158 Kamiya, T., 5 5 Kaufman, D., 386
Jones, G. P., 285 Karnla, C., 300 Kaufman, K. D., 312
Jones, G. W., 316 Kamo, J., 118 Kaugers, G., 136
Jones, J. B., 292 Karnohara, Y., 370 Kaura, A. C., 58
Jones, N. F., 376 Kampars, V., 170 Kavalek, J., 138
Jones, R. A,, 77 Kampe, M. M., 108 Kawabe, N., 332, 362
Jones, T. E., 367 Kan, K., 383 Kawada, Y., 14
Jonsson, E. U., 7 0 Kan, L. S., 268 Kawaguchi, S., 230
Joos, R., 33 Kanatomo, S., 206 Kawai, T., 65
Joshi, K. C., 139 Kanaoka, Y., 333 Kawamatsu, Y., 322
Joule, J. A., 233 Kaneda, M., 332 Kawamura, N., 368
Joulli&M.M., 55,90,117,192, Kaneda, T., 374 Kawarnura, Y., 53, 189
404 Kaneko, C., 234, 244, 248, Kawano, Y., 95
Joyce, C. J., 199 249, 250, 353, 406 Kawasaki, T., 121, 256
Judkins, B. D., 28 Kaneko, T., 166 Kawase, T., 173
Julia, S., 98 Kanemasa, S., 125, 126 Kawata, K., 193
Jullien, J., 151 Kanematsu, K., 383 Kawato, T., 230, 371, 381
Junek, H., 153,313 Kang, S. M., 110 Kawazura, H., 142
Junior, P., 327 Kano, S., 57, 147, 234 Kay, D. P., 318
Jurd, L., 310, 315, 316 Kantlehner, W., 265, 349 Kay, I. T., 181, 260
Juri, P. N., 370 Kantor, E. A., 283, 321 Kayumov, R. P., 1
Just, G., 55 Kapadia, Z., 308 Kazakova, 0. A., 8 7
Jynge, K., 116 Kaplan, L. J., 374 Kazrnaier, P. M., 320
Kaplan, M. L., 77 Keay, J. G., 233
Kaplina, N. V., 8 6 Keck, G. E., 273, 387
Kabachnik, M. I., 201 Kapoor, R. P., 300 Keifer, J. C., 320
Kabakov, A. P., 118 Kappe, T., 242, 270 Keiko, N. A., 321
Kabore, I., 394 Kapur, J. C., 55 Keller, P. C., 225
Kabuto, C., 408 Karady, S., 126, 282 Kellert, C. A., 28
Kachroo, P. L., 309, 314 Karakhanov, E. A., 298 Kelley, J. A., 342
Kadokawa, Y., 270 Karakhanov, R. A., 283 Kellogg, M., 313
Kaftory, M., 390 Karakasa, T., 291 Kellogg, M. S., 57
Kagami, H., 203 Karcher, B. A., 220 Kellogg, R. M., 237, 365,
Kagan, H. B., 9 Karhu, M., 359 367, 371
Kagan, J., 176 Karlsson, O., 8 2 Kelly, A. G., 403
Kahn, P., 285 Karpenko, L. P., 6 Kelstrup, E., 320
424 Author Index
Kemal, O., 268 Kira, M. A., 153 Kodama, M. Y., 20

Kemp, D. S., 206 Kirby, G. W., 248 Koehler, M., 114, 157
Kemp, M. S., 305 Kirchner, I., 252 Koenig, K. E., 374
Kende, A. S., 154 Kirilash, A. R., 104 Konig, K.-H., 281
Kennedy, E. R., 30 Kirk, A. R., 229 Koenig, M., 200, 201
Kepler, J. A., 314 Kirk, K. L., 221 KGnnecke, A., 215, 220
Kerfanto, M., 8 8 Kirkiacharian, B. S., 314 Koga, S., 259
Kermavner, V., 180 Kirkiacharian, S., 293 Koganty, R. R., 234
Kern, W., 386 Kirmse, R . , 170 Koguchi, K., 114
Kerton, N. A,, 252 Kisch, H., 25 Kohashi, Y.. 90, 350
Kervennal, J., 3 Kisin, A. V., 69 Kohlmeyer, I., 228
Kerwin, J. F., 56 Kiss, A,, 299, 309 Kohn, H., 186
Kessel, C. R., 398 Kissel, T., 67 Kojima, S., 259
Ketcham, R., 207 Kistenbruegger, L., 69, 369 Kolbah, D., 96, 224
Keyser, G. E., 268 Kister, J., 112 Kole, P. L., 293, 297, 314
Khabashesku, V. N., 7 2 Kita, Y., 121, 256 Kolenko, I. P., 13
Khaidukova, T. V., 19 Kitabashi, F., 8 9 Kollman, P. A., 348
Khaimova, T. G., 1 Kitada, Y., 256 Kolobova, N. E., 98
Khalil, Z . H., 5 5 Kitagawa, S., 407 Kolomiets, A. F., 41, 77, 330
Khan, M. A., 223, 243, 302 Kitagawa, T., 156, 212 Kolonko, K. J . , 269
Khan, Z . H., 199 Kitagawa, Y . , 236 Koloskova, N. M., 92, 147
Khand, U., 351 Kitahara, Y., 406 Kolt, R. J., 386
Khanna, R. N., 297 Kitajima, K., 181 Komatsu, M., 135, 307
Kharchenko, V. G., 293, 310, Kitazume, T., 120 Komissarov, V. N., 183
316, 319 Kito, Y., 198 Komlos, P., 153
Kharizomenova, I. A , , 86 Kivekaes, R., 185 Komori, T., 217
Khazanchi, R., 296, 307 Klaebe, A., 201, 202 Konakahara, T., 229, 261
Khetagurova, S. Sh., 329, 336, Klasinc, L., 355 Kondo, H., 6 8
350 Klayes, C. P., 69 Kondrateva, G. Ya., 218
Khidekel, M. L., 170 Klein, C., 140 Konefny, V., 8 4
Khisamutdinov, G. Kh., 187 Klein, M. W., 4 Kon’kova, S. G., 8 8
Khmelnitskii, L. I., 196, 386 Kleinpeter, E., 215 Kononenko, G. P., 304
Kholodov, L. E., 146 Kleinstuck, R., 2 9 Konstantinov, P. A,, 8 7
Kholodova, N. K., 1 Klich, M., 6 6 Konyaeva, I. P., 104
Khouri, F., 321 Kliewer, M. A,, 4 7 Konzelmann, F. M., 281
Khozeeva, R. V., 99, 111 Klimenko, S. K., 310 Koppenhoefer, B., 10
Khunt, V. N., 117 Klimovitskii, E. N., 350 Korbonits, D., 198
Khuong-Huu, Q . , 394 Klinga, M., 185 Koren, B., 66, 180
Kida, S., 322 Klingele, H. O., 188, 335 Kornet, M. J . , 164, 175
Kiely, J. R., 291 Klinkert, G., 146 Korodi, F., 309
Kiersznicki, T., 181 Kloek, J. A., 282 Korotenko, T. I., 345
Kigasawa, K., 55 Kloosterman, D., 253 Korshunova, K. M., 293
Kigawa, Y., 29 Klose, B., 13 Korte, F., 124, 135
Kikkawa, I., 57 Klotz, K. P., 321 Korytsky, 0. L., 112
Kikuchi, E., 261 Kmiotek-Skarzynska, I., 8 Kos, N. J., 268
Kikuchi, I., 155 Knaus, E. E., 236 Kosaka, S., 112, 278
Kilbee, G. W., 328 Knight, D. W., 149 Koshechko, V. G., 295
Kilina, L. V., 196 Knoll, K.-H., 9 2 Koshiro, A,, 270
Kim, J.-H., 139 Knutsson, L., 207 Koskikallio, J., 368
Kim, S. C., 22 Knyazev, V. N., 121 Kossanyi, J., 404
Kim, S. J., 158 Knyazhanskii, M. I., 9 7 Kost, A. N., 162, 164, 248
Kim, T. V., 201 Kobayashi, C., 252 Kostyanovskii, R. G., 30
Kim, Y.-H., 230 Kobayashi, G., 74, 110 Kosugi, H., 148
Kim, Y. I., 176, 177 Kobayashi, H., 76, 120, 152, Koszinowski, J . , 174, 221
Kimling, H., 332 401, 402 Kotake, H . , 147
Kimura, M., 187, 332 Kobayashi, K., 76, 161, 342 Kotelko, A., 345
King, J . F., 9 1 Kobayashi, T., 56, 136, 188, Kotlyar, S. A., 349
King, R . M., 305 342 Kotov, A. I., 170
King, T. J., 130 Kobayashi, Y., 61, 349, 357, Kotsuki, H., 407
Kingsbury, C. A . , 32 409 Kovaf, J., 84, 208, 209
Kingsbury, W. D., 51 Kobrin, V. S., 183 Kovaf, T., 344, 345
Kinoshita, H., 147 Kocevar, M., 180 Kovacic, P., 395, 398
Kinoshita, M., 268 Kochmann, W., 111 Kovtunenko, V. A., 213
Kinoshita, T., 136 Kocienski, P. J., 22 Kowala, C., 8 8
Author Index 425
Kowalczuk, M., 66 Kudai, T., 123 Lamotte, G., 98

Kowalewski, J., 76 Kudo, H., 294 Lampa, E., 125
Koyama, H., 45 Kudo, S., 161, 334 Lancaster, M., 52
Koyama, J., 242 Kuhla, D. E., 287 Landini, D., 368
Kozikowski, A. P., 35, 78, Kujundzic, N., 315 Landis, M. E., 51, 60, 177,
322 Kulibabina, T. N., 196 178
Kozlowska-Gramz, E., 35 Kulik, A. F., 386 Landor, P. D., 181
Kozuka, S., 65 Kulkarni, G. N., 146 Landor, S. R., 181
Kozyreva, L. V., 87 Kumadaki, I., 61, 349, 409 Lang, S. A. jun., 27, 110, 198
Kraatz, V., 124 Kumagai, T., 53, 189 Langridge, J. R., 230, 389
Kraemer, R., 409 Kumamoto, T., 357 Lanier, J . L., 192
Krajewski, J. W., 287 Kumar, A. , 296 Lanovaya, G . A., 195
Krantz, A., 44 Kumar, D., 312 Lanzilotti, A. E., 165
Krasnomolova, L. P., 114 Kurnar, G., 87 Laouenan, A,, 99
Kraus, G. A., 312 Kumar, P., 120 Laparra, J . , 283
Kraus, W., 2 Kumar, R., 127 Lapham, D. J., 103
Krause, D., 211 Kumar, S., 12 Laping, E., 134
Kravtsova, V. N., 316 Kumari, M., 314 Larchevesque, M., 334
Krawczyk, Z., 60 Kunert, D., 63 Larson, A. C., 398
Krebs, A,, 234, 332 KUO,H.-S., 153 Lasswell, W. L., 305, 306
Krebs, E. P., 180 Kuraishi, T., 212 Last, R. L., 268
Kreder, J., 55 Kurbanov, S. B., 103 Latif, M., 276
Kreher, R., 214 Kurita, J., 101, 248, 338, 340, Latif, N., 170
Krejcoves, J., 313 341 Lattes, A., 32, 33, 386
Kremlev, M. M., 118 Kurosawa, K., 314 Lau, H. H., 110, 180
Kresge, A. J., 168, 408 Kuroyan, R. H., 288 Laude, B., 216, 219
Kreuger, W. C., 323 Kurth, H. J., 314 Lauer, R. F., 341
Kreutzberger, A., 215 Kusano, Y., 245 Lauransan, J., 112
Krey, P., 184 Kushnarev, D. F., 75 Laurent, A., 35, 37, 39, 40,
Kricheldorf, H. R., 168 Kusumi, T., 188, 242 41, 159
Krief, A., 21, 26 Kutiu, H., 177 Laurent, J., 44
Krieger, C . , 172, 203 Kutney. J. P., 236 Lavergne, J. P., 218, 358
Krimer, M. Z., 41, 43, 44 Kutschy, P., 60 Law, K. K., 318
Krische, B., 186 Kuwabara, K., 128, 212 Lawesson, S.-O., 86
Krishna, R. R., 300, 354 Kuwada, Y., 219, 343, 344 Lawrie, K. W. M., 311
Krishnan, L., 249 Kuwajima, I., 151 Lazaris, A. Ya., 196
Krishna Mohan Rao, K. S. R., Kuwata, S., 89 Lazaro, R., 121
3 14 Kuzmenko, V. V., 183 Lazdin’sh, I. Ya., 223
Krishnamurthy, S., 22 Kuznetsov, N. V., 110 Lazovenko, A. N., 122
Krishnamachari, S. L. N. G., Kvitko, N. Ya., 99, 111 Leaver, D., 107
103 Kwast, A., 8 Lebedenko, N. Yu., 120
Krishnamoorthy, V., 326 Kyazimov, Sh. K., 3 Lebedev, N. N., 6
Kristian, P., 60 Kydyrov, R. A., 329 Lebedev, 0. V., 386
Kristofcak, J., 208 Kyler, K. S., 261 Le Be], N. A., 274
Krohnke, F., 210 Lebouc, A., 285
Krogsgaard-Larsen, P., 188 Lecas, A., 162
Krolevets, A. A., 330 Laatsch, H., 311 Leckonby, R. A., 399
Krolikowska, A., 192 L’abbk, G., 43, 70, 116, 135, Lecoq, J . C., 5
Krowicki, K., 232 143, 145 Le Corre, M., 147, 152, 283,
Krueger, C., 329 Labouta, I. M., 126 297, 298
Kruizinga, W. H., 237, 365 Lacombe-Bar, S., 35 Le Coustumer, G., 169
Kruse, C. G., 91, 324 Laerurn, T., 128 Ledon, H., 21
Krutosikova, A., 208 Lagutkin, N. A., 408 Lee, C. K., 158
Kryczka, B., 41 Lai, J. T., 240 Lee, C. M., 233
Krzyzosiak, W. I., 127 Laidler, D. A,, 377, 378 Lee, D., 320
Ku, H., 33, 400 Laitalainen, T., 185 Lee, G. E., 8
Kubas, G. J., 398 Lakatos, I . , 57 Lee, H. H., 114
Kubata, J., 215 Lakshmikantham, M. V., 172 Lee, J.-S., 72
Kubo, K., 128 Lal, B., 94 Lee, L.-C., 133
Kubo, T., 385 Lal, K. B., 133 Lee, S. K., 262
Kubo, Y., 59 Lalezari, I., 104, 135, 224 Lee, T. V., 27
Kubota, S., 95, 137, 138 Lamb, J. D., 368, 378 Lee, V. Y., 173
Kubota, T., 57, 326 Lambert, D. O., 106 Le Fevre, G., 179
Kucklinder, U., 160 Lambert, J. B., 256 Leffek, K. T., 369
426 Author Index
Le Floc’h, Y., 88 Linek, E. V., 57 Lutz, J. T. jun., 1

Le Floch-Perennou, F., 83 Linkies, A., 58 Lutze, G., 277
Le Goff, M. T., 162 Linstrumelle, G., 21, 62 Lynch, D. C., 405
Le Guillantoin, G., 285 Lipka, P., 111 Lyons, J. E., 3
Lehman, L. S., 45 Lipkin, A. E., 92 Lyra, D. A., 309
Lehn, J. M., 374, 381 Lipkowitz, K. B., 238 Lysenko, Z., 404
Lehr, R. E., 12 Lippmann, E., 215, 220 Lyubovskaya, A. E., 97
Lehtinen, L., 368 Lipshutz, B. H., 146 Lyuts, A. E., 114
Lehtonen, E. M. M., 148, 405 Lisini, A., 96, 345
Leigh, S. J., 375, 376 Lissee, M., 369
Leigh, W. J., 60, 178 Lister, J. H . , 224 Maas, G. E., 368
Lein, G. M., 374 Litkei, G., 1, 283 Mabry, T. J., 308
Leininger, H., 331 Littell, R., 165 Macaluse, G., 198
Leistner, S., 278 Little, R. D., 400, 401 McCabe, P. H., 407
Leitch, E., 182, 207 Litvinov, V. P., 97, 104 Maccagnani, E., 234
Lelj, F., 31 Litvintsev, I. Yu., 6 McCall, J. M., 253
Lemarchand, M., 103 Liu, J.-M., 399 Maccarone, E., 87, 103
Lemmetyinen, H., 368 Liu, K.-C., 133 McCarthy, B. L., 256
Lempert, K., 139 Liu, M. T. H . , 46 Macchia, F., 63
Lempert-Streter, M., 139 Liu, P. S., 342 Maccioni, A., 202
Le Nguyen, N., 147 Liu, Y. Y., 311 McCleery, P. P., 191
Lennon, M., 393 Livantsova, L. I., 65 McClelland, C. W., 168
Lenoir, D., 138 Llinares, J., 114 McClelland, R. A., 168
Lenz, W., 61, 69 Lloyd, D., 345, 363 McClure, D. E., 10
Leonard, N. J., 268,269, Lloyd, D. M. G., 331 Macco, A. A., 8 1
381 Lloyd, J. M., 232 McComsey, D. F., 247
Leong, T. S., 303 Lobanov, D. I., 201 McCord, T. J., 190
Le Quesne, P. W., 306, 309 Lobo, A. M., 49 McCready, R., 6
Lerche, H., 164 Lockard, J. P., 30 MacCross, M., 268
Lerstrup, K. A., 180 Lodge, S. P., 285 McCullagh, L., 389
Leschinsky, K. L., 282 Loebach, W., 136 McCulloch, A. W., 158
Lesiak, T., 125 Loeffler, W., 3 11 McCullough, D., 238
Leslie, T. M., 28, 33 Lofthouse, G. J . , 155 McDonald, E., 402
Lesniak, S., 37 Lohmann, J. J., 138 MacDonald, R. J., 193
Leung, C. W. F., 233 Lohs-,, C., 143, 234 Macdonald, T. L., 392
Le-Van, N., 3U8 Longobardi, M., 386 McDonough, L. M., 98
Levin, J. I., 224, 382 Looker, J. H., 288 MacDowell, D. W. H., 83
Levitz, R., 239 Loopstra, B. O., 360 McEvoy, T., 208
Levkovskaya, G. G., 110 Lopez, A., 32, 33 McEwan, W. E., 193
Levson, K., 32 Lopez, L., 10, 122 McFarlane, C. S., 288
Levy, A. B., 149 Loreto, M. A., 386 Machin, J., 183
Lewis, K. G., 150 Lorke, M., 60 Macho, V., 18
Lex, J., 360 Lotts, K. D., 198 Macias, A., 119
Ley, S. V., 42 Loughhead, D. G., 26 McInnes, A. G., 158
Liang, H. T., 328 Lo Vecchio, G., 190 Mack, A. G., 102, 230
Liberzon, R. M., 329 Lovell, F. M., 165, 301 Mack, M. P., 29, 348
Licandro, E., 182 Lovett, M. B., 68 Mackay, D., 196, 386
Lidert, Z., 266 Lovell, M. F., 198 McKelvey, R. D., 285
Lidia, M., 20 Low, J., 158 McKendrick, J. J., 295, 302
Liebman, A. A., 120, 311 Loy, G., 322 McKenzie, S., 212
Liebscher, J., 136, 142, 143, Lube, W., 242 McKenzie, T. C., 165
224, 277 Luber, J., 202 McKillop, A., 245
Liepins, E., 40, 126, 260 Lucas, M., 89, 386 McKinley, W. H., 213
Liles, D. C., 136 Lucchini, V., 44 McKinney, J. D., 153
Liljefors, S., 81 Luchian, C., 196, 207 Mackinnon, J. W. M., 248
Lim, K. H. R., 176 Ludovici, D. W., 218, 342 McLaughlin, A. R., 394
Lin, L.-C. C., 235 Lukac, J., 40 MacLeod, J. K., 15
Lin, X. Y., 328 Lukevits, E., 83 McMahon, S., 364
Lin, Y. I., 27, 110, 198 Luk’yanenko, N. G., 349, 368 McMonagle, D., 116
Lind, H . , 240 Lumma, W. C., 226 McMullan, E. E., 289
Lindgren, B., 186 Lupi, A., 304 McMullen, C. H., 25
Lindner, H. J., 399 Lurle, E. P., 13 McNab, H., 154, 262, 363
Lindoy, L. F., 364 Luthman, K., 157 MacNicol, D. D., 164, 295,
Lindsey, R. L., 178 Lutsenko, I. F., 65 302, 407
Author Index 427
McOmie, J. F. W., 214 Manabe, T., 390 Maryanoff, B. E., 158, 247,
McPartlin, M., 364 Mandal, A. K., 321 382
McQueen, R. G., 16 Mandolini, L., 79 Maryanoff, C. A., 382
Madajova, V., 122 Mandrugin, A. A., 118, 169 Marzin, C., 98
Madawinata, K., 42, 278 Mane, R. A., 110 Masuda, H., 261
Maddox, M. L., 264, 387 Mangold, D., 275 Masuda, K., 134, 135, 138,
Madec, C., 99 Manhas, M. S., 55 140, 206
Madoux, D. C., 60, 177 Manigand, C., 285 Masuda, R., 112, 278
Maeba, I., 214 Manimaran, T., 313 Masuda, S., 148
Maeda, T., 35, 95 Manke, K., 402 Masquelier, J., 283
Maekawa, M., 385 Manners, G. D., 310 Masquelier, M., 180
Markl, G., 72, 330 Mannschreck, A., 46 Massa, S., 335
Marky, M., 195 Manzini, P., 325 Masumura, M., 87, 212, 306,
Maffrand, J.-P., 87, 89, 386 Manzo, R. H., 232 327
Magagni, M., 112 Mao, Y., 249 Masuya, H., 95
Magdesieva, N. N., 92, 147 Mao, Y.-L., 52 Mataka, S., 140, 141, 228
Magee, W. L., 219 Maquestiau, A., 32 Matheson, R. A. F., 158
Maggi, D., 346 Marchese, G., 122 Mathis, R., 33
Magi, M., 40, 260 Marchesini, A., 38, 189, Mathur, S. S., 233
Magnane, R., 21 362 M a t h , S. A., 231
Magno, S. M., 325 Marchetti, L., 168 Matsuda, H., 25, 168, 299
Magnus, P. D., 62 Marchetti, M., 75 Matsuda, I., 20
Magolda, R. L., 404 Marei, M. G., 288 Matsuda, T., 370
Maguet, M., 115 Mares, F., 5 Matsuda, Y., 74, 110, 363
Mah, T., 3, 66 Margosian, D., 395 Matsugo, S., 67, 165
Mahaffey, R. L., 159, 398 Mariani, C., 369 Matsui, K., 389
Mahaim, C., 404 Mariman, E. C. M., 98 Matsumoto, H., 148, 322
Mahapatra, G. N., 110 Marinelli, E. R., 149 Matsumoto, K., 211, 231,
Maia, A., 368 Marini-Bettolo, G. B., 304, 246, 388
Maier, T., 265 309 Matsumoto, S., 13, 295
Maiolo, F., 78 Marino, E., 125 Matsumoto, T., 65
Maiorana, S., 174 Marino, J. P., 21 Matsumura, E., 231, 396
Mairesse-Ducarmois, C. A,, Mark, C., 9 Matsumura, H., 57, 215
331 Markham, J. L., 406 Matsunaga, T. O., 227
Maitlen, J. C., 98 Markosyan, A. I., 288 Matsuno, T., 266
Maitte, P., 295 Markov, V. I., 30 Matsuo, K., 277, 353
Majchrzak, M. W., 256, 345 Markova, L. I., 293 Matsuo, M., 13, 166, 295
Majeste, R., 140 Marquet, B., 41 Matsuo, T., 95
Majoral, J. P., 409 Marquez, V. E., 342 Matsuoka, K., 407
Mak, M., 57 Marron, N. A., 399 Matsuoka, T., 217
Mak, T. C. W., 362 Marsais, F., 243 Matsushima, K., 368
Makabe, O., 226 Marsh, W. C., 345 Matsushita, T., 38
Makhova, N. N., 196 Marshall, D. R., 345, 363 Matsuura, S., 306
Makosza, M., 8 Marshall, J. H., 77 Matsuura, T., 1, 12, 67, 68,
Maksimov, A. M., 85 Marshtupa, V. P., 164 165, 269, 307
Malatesta, V., 285 Marsili, A., 15, 218, 335 Matsuura, Y., 118
Malavaud, C., 202 Marsman, B., 10 Matsuzaki, K., 181
Malcherek, R., 352 Martel, H. J. J. B., 364 Matthews, R. S., 388
Malek, J., 147 Martens, C., 135 Mattingly, P. G., 56
Malhotra, S. C., 133 Martensson, N., 370 Matzinger, P., 402
Mali, R. S., 313 Martin, A,, 207 Mau, A. W.-H., 88
Malinina, L. A., 196 Martin, J. C., 186, 193, 264, Maurer, B., 285
Malkes, L. Ya., 87 387 Mauze, B., 9
Mallet, M., 230 Martin, L. D., 186 Maxey, K. M., 402
Mallick, I. M., 199 Martin, S. F., 388 May, G. L., 8 3
Malloy, T. B., 5 1 Martin, V. V., 183 Maycock, C. D., 42
Malpass, J. R., 398 Martino, R., 32, 33 Mayer, J. M., 373
Maltesson, B., 79 Martvon, A., 203 Mayer, R., 61
Mal’tsev, A. K., 72 Martynova, V. P., 283 Mayerle, J. J., 173
Mamedov, E. A., 1 Martyres, G., 310 Mayr, A., 369
Mamedov, E. Sh., 103 Marunouchi, K., 402 Mayring, L., 164
Mamedov, G. Kh., 19 Maruyama, I., 342 Maza, A., 20
Mamo, A,, 87, 103 Maruyama, K., 24, 59, 295 Mazumdar, A. K. D., 96
Manabe, O., 245 Maruyama, O., 148 Mazzanti, G., 234
428 Author Index
Medici, A., 129 Mingiardi, M. R., 107 Momose, T., 160

Medvedskaya, L. B., 218 Minkin, V. I., 97, 345 Moncada, S., 402
Meegan, M. J., 300 Minoli, G. 263, 353 Monforte, P., 117
Megera, I. V., 81 Mintas, M., 46 Mongelli, N., 290
Meguro, K., 219, 343, 344 Miocque, M., 218, 355 Montag, R. A,, 409
Mehrotra, K. N., 181 Mioskowsky, C., 8 Montanari, F., 368
Meier, H., 76, 134, 135 Mirskova, A. N., 110 Montastier, J., 77
Meinwald, J., 170, 284 Mishchenko, A. I., 30 Monti, L., 283
Melaw, C., 296 Mishchenko, V. F., 195 Moody, C. J., 184
Mellis, S., 322 Mishiev, R. D., 103 Moon, R. W., 261
Mellor, J . M., 385 Mishina, T., 21 Moore, G. G. I., 229
Melnick, B., 176 Mishrikey, M. M., 288 Moore, H. W., 6 3
Menachery, M. D., 309 Mison, P., 39, 40, 159 Moore, L. D. jun., 192
Mencarelli, P., 158 Misra, P. K., 8 4 Moore, R. E., 286
Meng, K., 139 Misra, S. C., 84 Moore, T. F., 77
Menicagli, R., 75 Mistrik, E. J., 1 Mootz, D., 345
Menschik, J., 8 8 Mitchell, J . C., 60 More, J . A,, 341
Menu, A., 32 Mitchell, W. R., 199 Morelli, I., 15, 218, 335
Mercer, F., 6 3 Mitin, N. I., 408 Moretti, I., 47
Merchant, J. R., 211, 310 Mitra, A. K., 62 Morgan, T. K., 394
Merenyi, R., 180 Mitra, R. B., 146 Morgos, J., 18
Merkle, U., 134 Mitscher, L. A., 130, 328 Mori, C., 262
Merrigan, K. A., 177 Mitsudo, T., 168 Mori, K., 8, 148, 270, 289,
Merten, R., 115 Mitsudo, T.-A., 240 342, 403
Mertens, W. J . , 94 Mitsugi, K., 268 Mori, M., 58, 161, 241, 245,
Messeguer, A., 296 Mittra, A. S., 8 4 334
Messmer, A., 215 Mitzlaff, M., 239 Morin, F. G., 32
Mester, I., 149 Miura, M., 122, 407 Morisawa, H., 268
Meszaros, Z., 270 Miyadera, T., 95 Morita, K., 35
Meth-Cohn, O., 78, 87, 146, Miyahara, Y., 7 4 Morita, M., 53, 359
224, 240 Miyasaka, T., 214, 255 Morita, N., 155
MetyS, J., 96 Miyashi, T., 28, 252 Morley, M. L. de B., 302
Metyiova, J., 8 5 Miyashita, W., 61, 349 Morlyan, N. M., 292
Metzger, J., 112, 188, 289, Miyata, N.. 12 Morosawa, S., 332
306, 365 Miyata, Y., 259 Morrissey, P., 278
Meunier, P., 99 Miyazaki, H., 291 Mors, W. B., 283
Mews, R., 140, 276 Miyazawa, K., 128, 212 Mortikov, V. Yu., 97
Meyer, G. R., 28 Miyazawa, T., 8 9 Morton, G. O., 27
Meyer, H., 253 Miyoshi, M., 246 Moscowitz, A., 323
Meyer-Dayan, M., 304 Miyoshi, S., 13 1 Moskowitz, H., 218, 355
Meyers, A. I., 229 Miyoshi, T., 268 Moss, S. F., 138
Meyerson, L. R., 386 Mizerski, T., 192 Mossini, F., 107
Mezheritskii, V. V., 155, 283, Mizrakh, L. I., 202 Motoki, S., 106, 203, 208,
288 Mizuno, Y., 242 291, 323
Michand, J., 283 Mkrtchyan, A. P., 102 Motoyoshiya, J . , 205
Michejda, C. J., 3 Modak, H. M., 41 Mound, W. R., 214
Michel, M., 8 Modelli, R., 69 Moussa, H. H., 95
Micromastoras, E. D., 194 Modena, G., 44, 369 Movsumzade, M. M., 19
Migliara, O., 357 Moderhack, D., 6 0 Moynihan, P., 181
Mignot, A., 218, 355 Moeller, E., 139 Mozetic-Rescic, B., 66
Mikhailov, B. M., 408 Morhle, H., 258, 345 Mozhaeva, T. Ya., 121
Mikhailova, T. S., 193 Moffet, R. B., 345 Mpango, G. W. B., 181
Miki, T., 95 Mohammadai, M. A., 1 4 Mraz, T. J., 21
MikSik, F., 85 Mohapatra, R. M., 84 Mrotzek, H., 44, 55, 115, 134
Milcent, R., 200 Mohr, S., 193 Muccino, R., 120
Miles, D. E., 186 Mohraz, M., 384 Muchowski, J . M., 264, 342,
Millen, P. W., 145 Mohsen, A., 357 381
Miller, A., 152 Moiseenkov, A. M., 4, 320 Miillen, K., 349
Miller, M. J., 56 Moldovanova, L. K., 286 Miiller, I., 270
Miller, T. G., 180 Molho, D., 304 Mueller, J. P. H., 314
Mills, N. C., 225 Molimard, J. C., 345 Mueller, K. H., 360
Mills, N. S., 20, 154 Molina-Buendia, P., 290 Miiller, N., 75
Mimoun, H., 9 Molle, L., 141 Mueller, P., 313, 317
Minakova, R. A., 8 7 Mollier, Y., 169 Mueller, W. M., 379
Author Index 429
Muenchausen, C. P., 367 Nagamoto, N., 160 Navech, J., 409

Mues, R., 308 Nagano, M., 95 Nawai, A., 273
Mukae, J., 151 Nagarajan, K., 130, 331 Nayak, A., 104, 117, 230,
Mukai, C., 319 Nagarajan, M., 158 368, 371
Mukai, T., 28, 53, 189, 252 Nagasawa, M., 17 Naylor, A., 142
Mukaiyama, T., 9, 104, 146, Nagase, K., 112, 278 Neckers, D. C., 165
150, 193, 224 Nagata, M., 53, 359 Nefedov, 0. M., 72
Mukkavilli, L., 55 Nagata, W., 57, 95 Nefedov, V. I., 118
Mukherjee-Mueller, G., 40 Nagayoshi, M., 215 Negita, H., 385
Mukhopadhyay, K. K., 302 Nagel, A., 271 Negurenko, V. M., 1
Mukidjam, E., 221 Nagar, A., 308 Neidert, E. E., 177
Mujamoto, S., 369 Nahm, S . , 252 Neidlein, R., 99, 155
Mujata, R., 363 Naidu, M. V., 314 Nei1and;O. Ya., 180
Muller, G. W., 400 Nair, M., 188 Neilands, O., 170
Muller, R. K., 33 Nair, M. D., 111, 130 Neilson, D. G., 215
Mullins, M. J., 91, 359 Nair, V., 268 Neiman, Z., 267
Mulot, P., 334 Naisby, T. W., 175, 337 Nelin, E. N., 164
Mulquiney, C. E., 150 Naito, T., 244, 406 Nelsen, S. F., 398
Mulvagh, D., 300 Najami, K., 36 Nelson, J. R., 25
Mulzer, J., 6 4 Najera, C., 239, 260 Nelson, P. H., 386
Mumtaz, S., 254 Naka, T., 135, 272 Nelson, S . D., 348
Mundy, B. P., 285 Nakadachi, K., 334 Nelson, S. F., 384, 385, 401
Muneyuki, R., 1 4 Nakagawa, M., 207 Nematollahi, J., 207
Munier, R., 317 Nakaguchi, O., 55 Nemes, I., 6
Munoz, A., 200, 201, 202 Nakajima, K . , 35 Neoh, S. B., 74, 147
Muradian, J., 307 Nakajima, N., 390 Nesnow, S., 302
Muradyan, L. A., 183 Nakamoto, K., 403 Nesterenko, D. P., 137
Murahashi, S.-I., 239 Nakamura, A., 35 Neszmelyi, A,, 215
Murai, H., 195 Nakamura, H., 67 Neudecker, T., 191
Murai, Y . , 226 Nakamura, K., 268 Neugebauer, D., 329
Murakami, M., 128 Nakamura, Y., 230 Neugebauer, F. A,, 175, 203
Murakami, T., 106, 188 Nakanishi, A,, 8 Neumann, W. P., 4 7 , 4 0 8
Murakami, Y., 363 Nakano, A., 363 Neunhoffer, H. 215
Muraki, S . , 408 Nakano, H., 208 Neve, J., 141
Muraoka, K., 217 Nakano, J., 317 Nevestveit, O., 52
Muraoka, M., 109 Nakano, K., 57 Newcomb, M., 49, 373
Murata, I., 90, 350 Nakano, T., 61, 148, 207, 349 Newcombe, P. J., 80
Murata, K., 12 Nakayama, J., 69, 324 Newkome, G. R., 104, 230,
Murata, S., 20, 25 Nakayama, M., 306, 327 368, 371, 381
Muresan, A., 112 Nakayama, T., 148 Newmark, R. A., 229, 320
Murphy, E., 393 Nakayama, Y., 147 Newton, R. F., 27, 164, 335,
Murphy, W. S., 387 Nakazawa, T., 165 375, 3 7 6 , 4 0 2
Murray, B. M., 407 Nakemura, E., 366 Ngi, L. N., 92
Murray, I. E. P., 130 Nalepa, C. J., 399 Nickell, D., 273
Murray, R. D. H., 311 Nalepa, K., 119 Nicoine, F., 98
Murti, V. A., 335 Namiki, M., 198 Nicolaescu, T., 119
Musavirov, R. S., 321 Nandi, B. B., 116 Nicolaisen, F. M., 204
Musgrave, W. K. R., 264 Nantka-Namirski, P., 214 Nicolaou, K. C., 366, 404
Musorin, G. K., 7 5 Naraki, T., 386 Nicolau, G., 88
Musorina, T. N., 321 Narasimhan, K., 18 Niculescu, I., 298
Musumarra, G., 87, 290, 391 Narasimhan, N. S., 313, 354 Nie, P. L., 290
Mutai, K., 7 6 Nardelli, M., 107 Nieberl, S . , 69, 327
Muzart, J., 2 3 Narine, B., 78 Nielek, S., 125
Myers, J . A., 192 Naruta, Y., 295 Nielsen, H., 319
Naseem, M. S . , 11 Nielsen, P. E., 234
Nasi, F., 191 Nienhaus, J., 112
Nabeya, A., 45 Nasipura, D., 17, 98 Nikolenko, L. N., 182
Nace, H . R., 7 Naso, F., 1 0 Nimura, N., 105
Nada, A. A., 114, 170 Nasu, I., 255 Ninagawa, A., 25, 168, 299
Nader, B., 216 Natalini, B., 299, 303, 347 Nishida, A., 403
Nafti, A., 39, 40, 159 Nath, J. P., 110 Nishida, S., 63, 390
Nagai, H., 8 Natsugari, H., 219, 343, 344 Nishigaki, S., 267
Nagai, T., 6 2 Natsume, M., 236 Nishikawa, Y . , 319
Nagai, Y., 148 Navarro, J., 9 4 Nishimoto, K., 38
430 Author Index
Nishimura, T., 95, 181 Ogawa, S., 403 Omura, S., 31 1

Nishinaga, A., 1, 307 Ogino, K., 65 Ona, H., 57
Nishino, K., 90, 350 Ogura, H., 105, 181, 259 Ondrus, T. A., 236
Nishio, T., 146, 390 Ohara, Y., 124 O’Neal, H. R., 319
Nishitani, Y., 57, 95 O’Hare, M. J., 177 O’Neil, R. M., 107
Nishiwaki, T., 205 Ohashi, M., 288 Ong, H. H., 336, ’386
Nishizawa, H., 407 Ohkawa, K., 148 Ono, N., 238
Nishizawa, Y., 28, 252 Ohkura, K . , 333 Ono, S., 354
Nitz, S., 135 Ohloff, G., 261, 405 Oohata, K., 186
Niu, S. L., 328 Ohmi, H., 155 Oono, Y., 120
Nivard, R. J. F., 98 Ohno, K., 208 Oppenheimer, ?\I. J., 227
Nivorozhkin, L. E., 345 Ohno, M., 332, 362 Oppolzer, W., ’298, 391
Niwa, M., 17 Ohno, S., 319 Oppong-Boackrie, F. K., 191
Nixon, W. J. jun., 150 Ohnuma, T., 408 Oraby, M., 273
Noda, M., 236 Ohsawa, A., 209, 210, 217, O’Regan, C. la., 181
Noe, C. R., 86, 99 262, 409 Orekhov, V. .N., 1, 5
Noth, H., 77 Ohsawa, T., 165, 359 Oremek, G., 90
Nofal, Z. M., 153 Ohshiro, Y., 205 Orena, M., 2.96
Nogradi, M., 297 Ohta, A., 174, 261, 262 Ors, J. A., 407
Noguchi, Y., 56 Ohta, H.. 297 Osajima, Y., 297
Nojima, M., 407 Ohta, K., 224 Osamura, Y‘., 38
Nomura, K . , 134, 135, 138, Ohta, N., 241 Osawa, T., 13, 198
140 Ohtsuka, Y., 259 Osbirk, O., 242
Nomura, R., 25, 168, 299 Ohya, T., 183 Oshima, T., 62
Nomura, T., 252, 306 Okada, K., 57 Osman, A , , !38
Nomura, Y., 195, 227, 239 Okada, M., 366 Ostapenko, E. G . , 87
Nonaka, T., 136, 197 Okada, T., 122, 315 Osterhout, K. R., 218, 342
Nonoyama, M., 92 Okahara, M., 368 Osteryoung, R. A., 317
Noravyan, A. S., 102 Okajirna, H., 333 Ostherheld, K . , 213
Nordenskiold, L., 76 Okajima, K . , 36 Osuka, A., 24
Norisue, H., 74 Okamoto, T., 259, 342 O’Sullivan, W. I., 97
Normant, H., 334 Okamura, H., 122 Osuntogun, B. A., 237
Noronha, R., 116 Okano, M., 63, 348, 355, 404, Otsuki, T., 12
Norris, A. R., 199 408 Ottridge, A. P., 7, 297
Norris, R. K., 80 Okawa, K., 35 Ottersen, T., 128, 302, 328
Norstroem, A., 153 Okawara, M., 184 Ottlinger, R., 61, 144
Noto, R., 79 Okawara, T., 56 Ouali, G., 30
Nov, E., 230 Okay, G., 350 Ouali, M. S., 195
Novikov, S. S., 196, 386 Okazaki, M., 54 Ovchinnikov, V. V., 200
Novitskaya, N. N., 91 Okazaki, R., 142 Overheu, W., 196, 266
Noyori, R., 14, 25, 401, 402 Okecha, S. A., 137 Overman, L. E., 191, 224
Nozaki, H., 22, 25 Okita, M., 58 Oyler, A. R., 76
Nummy, L. J., 11 Oklobdiija, M., 344 Ozawa, T., 295
Nunami, K., 246 Oku, T., 55 Ozegowski, R., 179
Nunomoto, S., 20 Okuda, H., 110
Nyburg, S. C., 72 Okuda, T., 385
Nye, M. J., 177 Okuda, Y., 137 Packard, A. B., 400
Nyholm, R., 370 Okunade, A. L., 308 Padhi, K., 112
Olah, G . A., 27, 76, 362 Padwa, A., 33, 34, 40, 152,
Oae, S., 31 Olekhnovich, L. P., 97 252, 400
Oberti, R., 167, 177 Oleinikova, L. V., 1 Pagnoni, U. M., 173
O’Callaghan, C. N., 297 Oleinikova, L. Ya., 92 Paintz, M., 306
Ochi, M., 407 OlivC, J.-L., 96 Pais, M., 35
Oda, J., 370 Ollis, W. D., 137, 144, 204 Pakkanen, T., 210
Odenthal, J., 234, 332 Olofson, R. A., 198 Palaniappan, R., 120
Odom, J. D., 77 Olsen, L. I., 283 PaleEek, M., 91
Oe, K., 216 Olsson, L. I., 147 Pallas, M., 111
Ogren, S. O., 78 Olstein, R., 5 Palui, G . D., 97
Oehler, E., 118 Omar, M. E., 357 Pancrazi, A., 394
Oelsner, J., 110, 251 Omar, M. T., 171 Pandit, U. K., 183
Ogata, H., 322 Ombetta, H.-E., 94 Panfilova, L. V., 79
Ogata, Y., 5 Omoji, B. U., 192 Pannell, K. H., 369
Ogawa, H., 151, 366 Omote, Y., 54, 55, 59, Panossian, S., 278
Ogawa, M., 236 390 Panouse, J.-J., 94, 112
Author Index 43 1
Panunto, T. W., 48 Pedersen, T., 205 Pietrusiewicz, K. M., 322

Panwar, P., 139 Pedra, A,, 289 Pietrzak, B., 406
Panzone, G., 267 Pedrini, P., 234 Pietsch, H., 58
Paolucci, C., 291 Peet, N. P., 37, 216 Piette, J.-L., 82, 104
Pappalardo, S., 367 Peled, M., 390 Pifferi, G., 191
Paquette, L. A., 14, 196, 211, Peled, N., 246 Pilipenko, V. S., 388
400 Pelizzi, G., 107 Pillay, K. S., 395
Paramasivam, R., 120 Pel’kis, P. S., 142 Pinhey, J. T., 83
Parasaran, T., 3 19 Pellacani, L., 386 Pinnick, H. W., 42, 186
Paraskewas, S., 229 Pellegrin, V., 176 Pinza, M., 191
Pardanani, J. H., 300 Pellicciari, R., 299, 303, 347 Pioch, D., 97
Pardoen, J. A., 218, 342 Pellissier, N., 39, 40, 159 Pipe, D. F., 184, 203
Parekh, K. S., 117 Pelosi, M., 192 Pirelahi, H., 292
Parg, A., 282 Peltzmann, R., 153 Pirisi, F. M., 368
Parham, J. C., 269 Pelz, N., 196 Pirkle, W. H., 48
Parikh, A. R., 117, 162 Pennings, M. L. M., 52 Piskunova, I. P., 209
Park, K.-H., 166 Pepe, G., 112 Piwinski, J. J., 235
Park, Y. H., 328 Percell, K. S., 398 Pizzo, G. P., 369
Parkanyi, C., 51 Perchonock, C. D., 246 Plat, M. M., 314
Parker, E. J., 70 Perekalin, V. V., 91 Plati, J. T., 281
Parker, J. E., 398 Perez, F., 151 Platonov, V. E., 85
Parker, K. A., 343 Pericas, M. A., 296 Platz, M. S., 399
Parkins, H., 3 15 Perjkssy, A., 76 Plenat, F., 169
Parlar, H., 135 Perkins, M. J., 209 Plenkiewicz, J., 203
Parmelee, W. P., 384, 401 Perkinson, N. A., 198, 301 Plescia, S., 343
Paronikyan, E. G., 368 Perozzi, E. F., 186 Pleshkova, A. P., 30
Parrick, J., 243, 254 Perrier, M., 205 Plieninger, H., 160, 395
Parry, M. J., 125 Perronnet, J., 137 Plum, H., 169
Parry, R. J., 91 Person, H., 36, 53 Plusquellec, D., 88
Parshad, R., 97 Perst, H., 274 Pocar, D., 265
Parteshko, V. G., 295 Pesce, G., 122 Pochat, F., 173
Paryzek, Z., 3, 16 Petasis, N. A., 366 Podda, G., 202
Passerini, N., 300 Pete, J . P., 23, 160 Podova, 0. A., 83
Pastorini, G., 325 Peter, R. K., 24 Podzolkova, 0. A., 18
Pastushok, V. N., 368 Peters, J. A,, 384 Poels, E. K., 91, 324
Patchett, A. A., 125, 126, Peters-Cranenburgh, P. E. J., Pogany, G. A., 1
231, 258, 282 384 Pohjala, E., 210
Patel, B. R., 230 Petillon, F. Y., 83 Pohl, H. H., 329
Patel, R. N., 232 Petrovanu, M., 196, 207 Pohl, S., 202, 204
Patel, S. G., 325 Petrovskii, P. V., 201 Poje, M., 288
Pathak, V. N., 139 Petrus, C., 209 Polikovi, J., 91
Patil, V. H., 110 Petrus, F., 209 Polanc, S., 234
Paton, R. M., 144, 199 Petruso, S., 357 Pole, J., 198
Patriarche, G. J., 331 Petrzilka, M., 391 Poleschner, H., 172
Pattenden, G., 252 Pettman, R. B., 377 Poliacikova, J., 209
Patwardhan, B. H., 70 Pevzner, M. S., 196 Politzer, P., 15
Paudler, W. W., 159, 398 Pews, R. G., 282 Polk, M., 319
Paul, V., 117 Pezzanite, J. O., 312 Pollard, M. D., 42, 178
Pauling, P. J., 285 Pfleiderer, W., 268 Pollicino, S., 291
Paulmier, C., 85 Pfister-Guillouzo, G., 210 Polonskaya, L . Yu., 202
Paulus, E. F., 7 Pfoertner, K.-H., 84 Polunin, E. V, 320
Pauson, P. L., 351 Pfund, R. A., 405 PomykiEek, J., 96
Pavia, M. R., 366 Pham, T. V. C., 308 Ponder, J. W., 403
Pavlickova, L., 175 Phatak, M. V., 333 Ponomareva, G. Z., 3
Pavlik, J. W., 290 Philipp, A., 325 Ponomareva, T. K., 86
Payard, M., 302 Phillion, D. P., 365 Ponsford, R. J., 55
Payne, L. G., 125, 258 Phillips, B., 51 Ponti, F., 157
Pearson, D. P. J., 376 Piade, J. J., 151 Ponticello, G. S., 162, 226
Pearson, G. D. N., 244 Piancatelli, G., 150 Poole, C. F., 32
Pechine, J. M., 151 Picard, J.-P., 72 Poon, Y. C., 72
Peck, L. W., 214 Piccolini, A., 167 Popelis, J., 126
Pedersen, C. L., 141 Pickardt, J., 175 Pople, M., 311
Pedersen, C. T., 205 Piepers, O., 367 Popova, A. G., 162
Pedersen, E. B., 242 Pietra, S., 263 Popova, E. P., 83, 244
432 Author Index
Popova, 0. A., 70, 171 Praefcke, K., 84, 184, 292, Rasrnussen, M., 364
Popp, F. D., 224 303 Rasshofer, W., 369
Popravko, S. A., 304 Rastetter, W. H., 11, 48, 365,
Porsch, P. H., 110, 180 Quast, H., 68, 179 406
Porter, A. E. A., 87 Queguiner, G., 103, 230, 243, Rastogi, M. K., 300
Porushnik, M. I., 81 262 Raston, C. L., 24, 218, 347
Porzi, G., 296 Quinteiro, M., 283, 285 Ratnarn, C. V., 257
Porzio, W., 157 Ratnikova, T. V., 123
Post, M. E., 274 Raasch, M. S., 90 Ratzenhofer, M., 25
Potapova, T. V., 408 Rabaron, A,, 314 Rau, D., 175
Potekhin, A. A,, 105, 146 Rabinovich, D., 327 Raude, E., 55
Potts, B., 192 Rachlin, S., 94 Rault, S., 92, 343
Potts, K. T., 101, 113, 125, Rackharn, A , , 288 Rawlins, M. F., 385
126, 192 Radak, R. E., 255 Rawson, D. I., 360
Poulton, G. A., 289 Radeglia, R., 277 Ray, S., 293, 297, 314
Povarov, L. S., 270 Rademacher, P., 384 Razdan, R. K., 294
Povarova, N. A., 196 Radford, T., 307 Razmara, F., 195
Povstyanoi, M. V., 386 Radhakrishna, A. S., 199 Razzini, A,, 158
Powell, A. M., 308 Radorn, L., 15 Reader, G., 106, 277
Prajsnar, B., 213 Radtke, V., 225 Ream, B. C., 25
Prakash, C., 325 Raffauf, R. F., 306, 309 Reamer, R. A., 126, 282
Prakash, O., 121 Rafferty, P., 102 Reamoan, L. S. S., 97
Pralus, M., 5 Raghu, S., 126 Rebek, J., jun., 6
Prasad, G., 181 Rahirni-Rastgoo, S., 232, 390, Reboul, J . P., 112
Prashad, V. M., 224 39 1 Recktenwald, R., 68
Pratt, J. W., 73 Rahkarnaa, E., 63 Reddy, G. S., 256
Presenti, M. T., 167 Rahman, M. 0. A. , 153 Reddy, K. K., 256
Press, J. B., 75, 94, 355 Rahman, M. T., 8 3 Reddy, N. J., 305
Preston, P. N., 130 Rahman, W., 305 Redlich, H., 404
Preti, G., 90 Rai, R., 142 Redolfi, P., 308
Preuschhof, H., 157 Raisanen, K., 6 3 Reeder, R. A , , 49
Previtera, T., 117 Raithby, P. R., 383 Reedijk, J., 155, 183
Price, C. C., 319 Rajagopalan, K., 87 Rees, C. W., 51, 102, 121,
Price, M. E., 68 Rajapaksa, D., 154 184, 203, 245, 280, 356
Prielipp, L., 96 Rajappa, S., 111 Reese, C. B., 268
Priklonskikh, G. I., 86 Rajca, A., 181 Regitz, M., 124, 134, 191
Prince, R. J., 167 Rajh, H. M., 98 Regitz, R., 250
Prinzbach, H., 331 RajSner, M., 85, 9 3 Reich, H. J . , 240, 398
Prochizka, M., 91 Rakhmankulov, D. L., 283, Reid, D. H., 109, 204, 205,
Procter, G., 167, 243 321 212
Proctor, G. R., 393 Rall, G. J. H., 327 Reinecke, M. G., 97
Profitt, J. A., 336 Ram, B., 55 Reinhoudt, D. N., 52, 350,
Proinov, L., 137 Rarnadas, S. R., 8 8 367
Prokofev, A. I., 201 Rarnage, R., 74 Reisch, J . , 149
Prokof’ev, E. P., 408 Rarnakrishnan, V. T., 120, Reisman, D., 327
Prokofeva, T. I., 201 313 Reissenweber, G., 275
Proksch, A., 61, 144 Rarnalingarn, K., 291 Reissig, H. U., 60, 173, 174,
Prosyanik, A. V., 30 Rarnan, K . P., 387 178
Protiva, M., 85, 92, 96, Ramana, D. V., 77 Reiter, F., 111, 197
331 Ramdani, A., 176 Rej, R. N., 314
Przylycki, J., 258 Rarnm, P. J., 318 Rejto, M., 88
Psaehr-Wirtz, M., 116 Rarnos Raimundo, I., 149 Rekers, J. W., 206, 400
Pschigoda, L. M., 323 Rarnsden, C. A., 137, 144, Remizov, A. B., 350
Puar, S., 334 204 Remy, D. C., 247, 393
Pudovik, A. N., 200 Rarnsh, S. M., 118 Renaud, R. N., 87
Pujari, H. K., 125, 133 Randall, M . J., 125 Rene, L., 98, 180
Pujol, F., 113 Rao, A. S. C. P., 61 Renfrew, A. M., 153
Pullman, B., 268 Rao, G. S. K., 314 Renson, M., 108
Purchit, A. K., 333 Rao, J. M., 305 Rentzea, C. N., 272
Pusset, J., 162 Rao, K. V. J., 305 Resetova, T., 138
Puttins, U., 170 Rao, P. L. K. M., 314 Reuschling, D., 58
Powell, M. F., 168 Rapoport, H., 393 Revelle, L. K., 71
Powers, D. E., 71 Rapp, U., 345 Reynaud, P., 293
Pozharskii, A. F., 224 Rasmussen, J. K., 320 Reynolds, D. P., 402
Author Index 433
Reynolds, G. A., 286, 292, Roedig, A., 285 Rys, B., 352
293, 306 Roeschenthaler, G. V., 71 Ryu, E. K., 268
Reynolds, G. F., 318 Roesky, H. W., 367 Rzaeva, A. S., 3
Reynolds, W. F., 72 Roettele, H., 362
Rezende, M. C., 290 Rogers, D. N., 233 Saakyan, A. M., 286
Reznikov, V. A., 183 Rogers, D. Z., 11 Sabahi, M., 360
Rhouati, S., 240 Rogers, R. D., 160 SabljiC, A., 96, 355
Ri, T., 357 RogiC, M. M., 348 Sabongi, G. J., 232, 390, 391
Ribo, J. M., 160 Rohr, W., 281 Sabri, S. S., 31
Ricard, M., 63 Roitman, J. N., 315, 316 Sachdeva, M. L., 133, 161,
Ricart, G., 117 Rokach, J., 106, 164, 277, 162, 181, 195
Ricci, A., 299, 347 281, 288 Sachdeva, Y. P., 300, 354
Rice, K . C., 101, 243 Rollema, H., 94 Sacquet, M. C., 295
Richard, H., 395 Roma, G., 300 Sadeghi-Milani, S., 135
Richard, T. J., 406 Romanov, N. A., 321 Sadri, E., 209
Richardson, F. S., 58 Romanov, N. N., 128, 133 Saegusa, T., 161, 342
Richardson, S. G., 268 Romeo, C., 307 Saeki, H., 365
Richardson, W. H., 68 Romeo, G., 345 Safarik, I., 43, 44, 134
Richarz, W., 2 Ronsisvalle, G., 73 Safaryan, A. A., 8 8
Richman, J. E., 363 Ronzini, L., 10 Safir, S. R., 75, 94, 355
Richter, C., 220 Rooney, C. S., 288 Safronova, Z. V., 60, 191,
Richter, M. J., 196 Rooney, R. P., 320 280
Richter, P., 357 Rorabacher, D. B., 367 Sagitullin, R. S., 248
Ricke, R. D., 315 Rosati, R. L., 278 Sahlberg, C., 157
Ridd, J. H., 212 Rose, C. B., 385 Saikachi, H., 156, 212
Ridge, D. N., 8 8 Rosenmund, P., 209 St-Jacques, M., 352
Ried, W., 90 Ross, J. F., 144 Saint-Roch, B., 72
Riehl, J. P., 58 Ross, J. P., 224 Saito, H., 245
Rigaudy, J., 406 Rossi, F., 125 Saito, I., 12, 67, 165, 269
Righetti, P., 167, 177 Rossi, S., 358 Saito, J., 45
Rinaldi, P. L., 48 Rossy, P. A., 75 Saito, T., 106, 268
Riobe, O., 285 Roth, H. D., 398 Saji, T., 315
Rion, K. F., 229 Roth, K., 71 Sakaguchi, M., 259
Risitano, F., 190, 273 Roth, M., 55 Sakaguchi, T., 183
Risse, G., 215 Roumestant, M. L., 17 Sakai, I., 332, 362
Rittle, K. E., 247, 393 Roussel, B., 77 Sakai, J., 95
Rivera, J., 407 Roussel, C., 112, 289 Sakakibara, M., 289
Rizvi, H., 254 Roussey, J. C., 219 Sakakibara, T., 41
Rizvi, S. Q. A., 48 Roussi, G., 161, 162 Sakamoto, M., 59, 128, 212
Rizzo, V. L., 136 Rout, D. N., 110 Sakamoto, T., 213, 230, 254
Robba, M., 92, 343 Roux, D., 47 Sakamoto, Y., 147
Robert, A., 111 Roux, D. G., 327 Sakanishi, K., 67
Robert, J. B., 200 Rowson, G. P., 137 Sakiyama, F., 165
Robert, J.-F., 94, 112 Royall, S. E., 388 Sakla, A. B., 316
Roberts, D. A., 298 Royer, R., 98 Sakovich, T. V., 101, 102
Roberts, D. K., 369 Rozynov, B. V., 304 Saksena, A. K., 398
Roberts, F. E., 115 Rubio, V., 253 Sakuma, Y., 270
Roberts, J. J., 403 Ruccia, M., 198 Salakhutdinov, R. A,, 323
Roberts, P. M., 56 Rudenko, B. M., 5 Saldabols, N., 126
Roberts, T. D., 135 Rund, J. V., 225 Saleh, S. A., 214
Roberts, T. G., 273 Runova, E. A., 298 Salim, V. M., 164
Roberts, S. M., 27, 402 Russ, P., 311 Sallay, P., 18
Robins, D. J., 146 Russo, F., 139 Salomon, M. F., 407
Robins, R. K., 266 Rusznak, I., 18 Salomon, R. G . , 407
Robinson, H., 305 Rutledge, P. S., 114 Salyn, Ya. V., 118
Robinson, J. F., 138 Ruzicka, V., 283 Samaan, J . H., 16
Robson, N. S., 388 Ryabokobylko, Yu. S., 329 Samarina, L. A., 152, 153
Rocchiccioli, F., 35 Ryabukhin, Y. I., 288 Samat, A,, 365
Rockley, J. E., 102 Ryan, C. J., 291 Sammes, M. P., 233
Rodighiero, P., 325 Ryan, R. R., 398 Sammes, P. G., 231, 234, 388,
Rodios, N. A,, 194 Ryang, H.-S., 182, 406 406
Rodrigues, J. A. R., 102, 245 Rybina, G. I., 293 Sammour, A., 114
Rodriguez, A., 150 Rybinov, V. I., 179 Samsonova, N. V., 86
Rodriguez Palacio, C. R., 149 Ryntz, R. A., 4 Samuel, C. J., 406
434 Author Index
Sanchez, M., 200, 210 Sberze, P., 307 Schreiber, J., 33

Sander, J., 279 Scarborough, R. M. jun., 152 Schriewer, M., 408
Sandhu, J. S., 190 Scala, A., 13, 7 0 Schroeder, G., 362, 367, 369
Sandifer, R. M., 317 Scarlata, G., 87 Schubert, E., 127
Sandra, P., 26 Scarpati, R., 182 Schubert, H., 111
Sandri, E., 291 Scarpone, S., 238 Schubert, U., 266
Sandri, S., 296 Scartoni, V., 15, 218, 335 Schuck, E., 227
Sangita (Miss), 125 Scettri, A., 150 Schulte-Elte, K. H., 405
Sanjoh, H., 405 Schaal, C., 6 3 Schultz, A. G., 156, 158, 251
Santagati, A,, 139 Schaap, A. P., 51, 66, 67 Schultz, P. G., 160
Santagati, M., 139 Schaart, F. J., 180 Schulz, R., 96, 135, 197
Santaniello, E., 157 Schafer, H., 85, 242 Schuman, C. A., 1 4
Sano, T., 332 Schaper, W., 194 Schurig, V., 9, 10, 32
Santos, E., 386 Scharf, H. D., 169 Schuster, G. B., 68
Sapevalov, A. Ya., 13 Schaub, B., 386 Schweig, A., 96, 135, 197
Sapunov, V. N., 6 Schaumann, E., 40, 44, 55, Schweitzer, D., 172
Sardello, D. J., 389 56, 60, 71, 114, 115, 134, Schweizer, W. B., 405
Sargent, C. R., 252 135 Schwertfeger, W., 323, 399
Sarkar, A., 98 Schaus, J. M., 247, 388 Scoby, J., 135
Sarma, C. R., 300, 354 Scheeren, J. W., 148 Scorrano, G., 369
Sarpal, P. D., 325 Scheffers-Sap, M. M. E., 112, Scott, D. C., 368
Sarpotdar, A. S.. 28, 33 384 Scott, G., 122
Sarti-Fantoni, P., 188 Scheffler, K., 202 Scott, J. C., 170
Sasaki, A., 193 Scheibe, R., 118 Scott, P. W., 166, 206, 212
Sasaki, H., 156, 212 Scheiber, P., 384 Scriven, E. F. V.,'146, 164,
Sasaki, M., 148 Schnell, F. M., 398 224, 335
Sasaki, T., 211, 381, 390, Schembri, G., 171, 323 Scrocco, E., 15
395, 407 Schenone, P., 386 Scrowston, R. M., 73, 96,
Sasaki, Y., 252 Scherowsky, G., 200 107, 356
Sasakura, K., 343 Schickaneder, H., 56, 174 Scully, F. E., 239
Sashida, H., 339 Schiessle, R., 330 Secci, M., 202
Sasse, M. J., 194 Schiffer, R., 174 Secor, H. V., 53
Sasse, W. H. F., 88 Schilling, M. L. M., 398 Seebach, D., 10, 173
Sastre, A , , 386 Schipper, P., 210 Seelinger, R., 71
Satake, K., 332 Schirmann, J. P., 5 Sega, A., 96, 345
Sataty, I., 246 Schlageter, M. G., 386 Segall, E., 71
Satge, J., 72 Schlangstedt, D., 200 Seguil-Camargo, L., 99
Sato, K., 148, 214, 288 Schleckker, R., 173 Segura, P. M., 113
Sato, M., 64, 157 Schleker, W., 169 Seha, Z., 92
Sato, R., 64, 240 Schlosser, M., 147, 237 Sehgal, C. K., 309, 314
Sato, S., 136, 352 Schmid, H., 40, 109, 195 Seidl, M. C., 164
Sato, T., 401, 402 Schmid, M., 294 Seifert, C. M., 27, 110
Sato, Y., 188 Schmidpeter, A., 71, 200, 202 Seiler, W., 25
Satsumabayashi, S., 208, 323 Schmidt, A., 387 Seitz, G., 196, 266
Sattler, K., 85, 242 Schmidt, J., 199 Seitz, S. P., 366
Sattsangi, P. D., 268 Schmidt, J. M., 60 Seki, E., 69, 324
Satyamurthy, N., 291 Schmidt, S. P., 68 Sekine, T., 197
Sauerbrey, K., 7 1 Schmidt, U., 9, 118 Sekine, Y., 236
Sauer, J., 387, 399 Schmitt, G., 216 Seko, N., 161
Sauers, R. R., 405 Schmitz, A., 124 Sekuja, K., 261
Saunders, D. W., 233 Schmitz, E., 34, 45, 157 Selby, T. P., 131
Saunders, J. K., 96 Schmiz, C., 301, 350 Selim, M., 114
Saur, M., 283 Schneider, B., 157, 404 Semenenko, N. M., 118, 169
Sauriol-Lord, F., 352 Schneider, P., 237 Semenov, V. P., 105, 146
Saus, A., 116, 117 Schneidewind, E., 306 Semenovskii, A. V., 320
Savard, M., 87 Schnutzler, R., 71 Sen, A. K., 110, 127
Savrasova, E. M., 1 Schoellkopf, U., 42, 110, 146, Senda, S., 256, 257
Sawai, H., 165 180, 191, 261, 278 Sendo,,Y., 9 5
Sawanishi, H., 101, 102, 248, Schoernaker, H. E., 118 Senga, K., 267
338, 339 Schonafinger, K., 263 Senning, A., 144
Sawhney, S. N., 121 Schoenecker, B., 326 Senter, F., 139
Sawicki, R. A., 360 Schoneweiss, S., 9 2 Seoane, C., 283, 285
Sawlewicz, J., 125 Scholl, H. J., 117 Sequin, U., 14
Saxena, J. P., 129, 139 Schomburg, D., 71 Serebryakov, B. R., 6
Author Index 435
Serebryakov, E. P., 28 Sherwin, M. B., 8 Simpkin, B. Ya., 97

Sergeeva, G. N., 350 Sherwood, A. G., 4 3 Simonen, T., 185
Sergeichik, V. V., 169 Shevchuk, M. I., 81 Simonet, J., 367
Serra-Errante, G., 234 Shevyrev, A. A., 183 Simonov, A. M., 92, 183
Serve, D., 207 Shiba, T., 171 Simonov, V. I., 183
Sessions, R. B., 385, 397 Shibamoto, T., 261 Simonsen, S. H., 186
Sethna, S., 300, 325 Shibasaki, M., 403 Simonyan, L. A., 60, 191, 280
Settimj, G., 345 Shibata, K., 326 Simov, D., 105, 120, 146
Seva, A., 346 Shibata, T., 138 Simpkin, D. J., 226,387
Severing, T., 164 Shibuya, I., 169, 226 Simpson, R. A,, 393
Sevin, A., 33, 47 Shibuya, M., 95, 137, 364 Sims, J. A., 25
Seybcld, G., 100, 125 Shibuya, S., 57, 147 Sinclair, I. W., 125
Shabanov, A. L., 19 Shim, S. C., 168, 240 Sindona, G., 31
Shafiee, A., 104, 135, 224 Shimada, K., 20 Sinha, N. D., 310
Shafiullah, G. M. A., 3 0 Shimizu, H., 124, 277, 319, Sinha Roya, D. K., 302
Shah, S. C., 371 353 Singh, A., 127
Shaida, W. A., 305 Shimizu, K., 53, 189 Singh, H., 128, 133, 183
Shaio, M. -J., 361 Shimizu, T., 1, 4 Singh, P., 183
Shakhtakhtinskii, T. N., 103 Shine, S. G., 262 Singh, R. P., 140
Shakova, L. M., 152 Shinkai, S., 245 Singh, S. P., 121, 386
Shalavina, I. F., 8 9 Shinogi, I., 8 9 Singh, V., 97, 140
Shams El-Dine, S. A., 125, Shipchandler, M. T., 224 Sinnreich, J., 66
126, 139 Shipov, A. G., 6 9 Sinyakov, A. N., 176, 182
Shaneyfelt, D. L., 288 Shirahate, K., 311 Sipio, W. J., 404
Shang, T. M., 328 Shirai, K., 357 Siporska, E., 320
Shankarnarayan, V., 211 Shiraishi, H., 123 Sirat, H. M., 3, 6 6
Shanta, M., 233 Shirataki, Y., 307 Sisti, M., 290
Shanzer, A., 357 Shirwaiker, G. S., 146 Siv, C., 188
Shapiro, R. H., 269 Shoenholzer, P., 360 Sivarambabu, S., 305
Sharapov, V. A., 383 Shoffner, J. P., 123 Skinnemoen, K., 292
Share, N. N., 288 Shortridge, T. J., 206 Skipper, P. L., 9 4
Sharif, A. B. M., 191 Showell, G. A., 257 Skoetsch, C., 110, 217, 228
Sharkova, L. M., 153 Shreeve, J. M., 157 Skvortsov, I. M., 223
Sharma, A. H., 209 Shridhar, D. R., 94, 300, 354 Skvortsov, N. K., 193
Sharma, K. S., 97, 140 Shudo, K., 12 Skvortsova, G. G., 275
Sharma, N. D., 315 Shubina, Yu. V., 34 Slack, D. A., 226
Sharma, P., 391 Shul’man, M. D., 110 Slanina, Z., 47
Sharma, R. P., 306, 310 Shul’ts, N. A., 78 Sleiter, G., 158
Sharma, S. C., 187 Shupik, R. I., 8 7 Sliwa, W., 223
Sharma, S. D., 55 Shusherina, N. P., 388 Sloboda, A. E., 88
Sharma, T. C., 303, 304, 305 Shustov, G. V., 30 Slouka, J., 215
Sharp, D . W. A., 8 3 Shustov, L. D., 182 Smagin, V. M., 6
Sharp, J. T., 175, 336, 340 Shvartsberg, M. S., 176, 182 Smalberger, T. M., 309
Sharpless, K. B., 5 Shevedov, V. I., 101, 102 Smale, T. C., 56
Shashkov, A. S., 408 Shvetsov-Shilovskii, N. I., 137 Small, R. D., 33
Shatin, N. T., 318 Siddiqui, M. S. S., 116 Smalley, R. K., 37, 180, 224
Shaw, G., 223 Sidell, M. D., 206 Smart, B. E., 257
Shaw, J. T., 261 Sidhaye, A. R., 252 Smets, G., 194
Shawali, A. S., 138 Sidorchuk, I. I., 1 Smid, J., 371
Shcherbakov, A. A,, 169, 319 Sidorenko, G. V., 72 Smirnov, V. N., 329, 408
Shcherbakov, A. K., 298 Siegbahn, K., 370 Smirnova, N. S., 293
Shchukin, G. I., 181, 183 Siegemund, G., 323 Smirnova, 0. D., 408
Shea, K. J., 382 Sieh, D., 3 Smirnova, V. A., 99, 111
Shebaldova, A. D., 316 Sieler, H. J., 170 Smirnov-Zamkov, I. V., 95
Shechter, H., 46, 158, 188, Siemionko, R. K., 399 Smit, F., 382
219, 316 Sievers, R . E., 269 Smit, V. A., 41, 43, 44
Shegal, I. L., 123 Sifniades, S., 160 Smith, A. B. tert., 152
Sheinkman, A. K., 164 Siles, S., 391 Smith, D . G., 158
Sheinson, R. S., 6 8 Silhavy, P. 147 Smith, D. J. H., 52, 69, 186,
Sheldrick, W. S., 7 1 Silverman, R. B., 255 385
Shen, M., 156, 158, 251 Silvestro, A., 117 Smith, D. M., 183
Shenberg, N. A., 118 Simes, J. H. H., 16 Smith, D. R., 190
Sheppard, W. A., 370 Simionovici, R., 20 Smith, H. K., 320
Sheradsky, T., 230 Simiti, I., 112 Smith, I. S., 144
436 Author Index
Smith, N. P., 46 Spirova, S., 325 Storr, R. C., 57, 194

Smith, R. H., 180 Spoormaker, T., 320 Stradi, R., 161, 162, 181, 265
Smith, R. J., 364 Sprague, P. W., 135 Strathdee, R. S., 336, 340
Smith, S., 256 Spreecher, M., 327 Strausz, 0.P.,43,44, 134,170,
Smithson, T. L., 63 Springer, J. P., 311 195
Smith-Verdier, P., 383 Sprio, V., 357 Streef, J. W., 334
Smolanoff, J., 284 Spur, B., 286 Streith, J., 218
Smolinski, S., 217, 352 Sreenivasan, R., 111 Strelets, B. K., 141
Snieckus, V., 82, 339 Srinivasan, R., 238, 407 Strosberg, A. M., 386
Snowden, R. L., 391 Srivastava, P. P., 121, 266 Struckov, Y U . ’ ~79,
. , 169,
Snyder, J. P., 51, 385, 401 Srivastava, S. L., 121 319
Sobczak, J., 6 Staab, H. A., 172 Stubbs, M. E., 48
Sobotka, W., 1 Stadtbauer, W., 270 Stuckler, P., 374
Sochilin, E. G., 18, 118 Staehle, M., 147 Studebaker, J., 238
Sodd, J. S., 249 Stalschus, J., 117 Studenikov, A. N., 105, 146
Soderquist, J. A., 384 Stam, C. H., 382 Stukalov, Yu. V., 5
Sogah, G. D. Y., 372 Stamegna, A. P., 193 Suami, T., 403
Sohar, P., 110 Stamm, H., 36, 188, 316 Sucrow, W., 175
Sokhatskaya, 0. M., 257 Stanborough, M. S., 212 Suss, R., 336
Sokol, L. S. W. L., 367 Staninets, V. I., 95 Sugai, S., 188
Sokolovskaya, S. V., 286 Stanley, K. L. M., 175, 337 Sugasawa, T., 343
Sokol’skii, G. A., 77 Stanovnik, B., 66, 104, 111, Sugawara, T., 14, 95
Soliman, E. A., 114 180,223,234,256 Sugden, J. K., 84
Soliman, F. S. G., 126 Staren’kii, A. G., 295 Suggs, J. W., 244
Solis, C. H., 3 Starewicz, P. M., 398 Sugi, H., 55
Solodovnikov, S. P., 201 Starker, B., 172 Sugimori, A., 370
Solz, B. L., 356 Starkov, S. P., 3 13 Sugimoto, H., 94, 129, 344
Somei, M., 244, 248, 406 Stasko, A., 61 Sugimura, H., 122
Sommer, S., 156, 266 Stec, W. J., 330 Sugita, T., 18
Soni, R. P., 129, 139 Stefancich, G., 335 Sugiyama, H., 269
Sonnay, P., 261 Stegel, F., 158, 290 Suguro, T., 148
Sonoda, T., 120, 152 Stegelmeier, H., 360 Suguyama, I., 257
Sonveaux, E., 227 Stegmann, H. B., 202 Sukhanov, S. V., 122
Sopchik, A. E., 32 Steigel, A., 387 Suksamrarn, A., 402
Sorci, M. G . , 368 Steimecke, G., 170 Sultanbawa, M. U. S., 319
Sorokin, M. F., 5 Steinbeck, K., 321 Sum, P. E., 404
Sorriso, S., 14 Steinberg, H., 406 Sumegi, L., 6
Sosnovskikh, V. Ya., 88 Stella, L., 180 Sumita, M., 55
Sotgiu, F., 322 Stenberg, J. F., 306, 318 Sumitorno, H., 366
Sotheeswaran, S., 319 Stenberg, V. I., 386 Summers, L. A., 102
Soti, M., 110 Stenhede, U., 69, 113 Sundermeyer, W., 71
Soto, J. L., 283, 285 Stepanova, A. A,, 137 Sundholm, E. G., 283,318
Sotoyama, T., 149 Stepanova, Z . V., 275 Sung, T., 32
Soucek, M., 175 Stephanidou-Stephanatou, J., Sunjid, V., 96, 224, 344, 345,
Soucy, D., 361 194 355
Sousa, L. R., 367 Stephenson, E. F. M., 5 Sunman, G., 301
Southern, P. F., 192 Sterber, V., 138 Surzur, J.-M., 91
Southgate, R., 55, 56 Sternbach, D., 364 Surpateanu, G., 196, 207
Southon, I. W., 235, 356 Sternhell, S., 52, 8 3 Suri, J. L., 326
Soyagimi, H., 236 Sterzycki, R., 1 Suri, S. C . , 66
Soyer, N., 88 Stetter, H., 112 Suschitzky, H., 87, 102, 146,
Sozu, I., 128 Steudle, H., 188 155, 164, 224, 230, 301,
Spada, A. P., 290 Stevens, I. D. R., 46 335, 354
Spada, L. T., 66 Stevenson, G. R., 176 Sutherland, I. O., 375, 376
Spagnolo, P., 163 Stewart, A., 407 Sutherland, J. K., 16
Sparatore, F., 264 Stjernstrom, N., 78 Suzuki, A., 149
Sparks, D., 395 Stick, R. V., 168 Suzuki, E., 287
Spaulding, T. C., 386 Stihel, Z., 361 Suzuki, H., 21, 291
Speckamp, W. N., 118 Still, I. W. J . , 303 Suzuki, M., 25, 246
Spencer, J. A,, 60 Stille, J. K., 148 Suzuki, N., 67, 132
Spencer, N., 375 Stoddart, J . F., 377, 378, 381 Suzuki, S., 55
Spinelli, D., 79 Stolbora, T. V., 310 Suzuki, T., 408
Spirikhin, L. V., 91 Stoodley, R. J., 42, 58, 223 Suzuki, Y., 64,157
Spirkovi, K., 84 Stork, G., 239, 366 Suzuta, Y., 242
Author Index 437
Svanholt, H., 72, 135 Talukadar, P. B., 132 Terekhin, A. A., 316
Svatek, E., 93 Tam, S. W., 318 Ternay, A. L. jun., 319
Svensson, L., 78, 82 Tamas, J., 57, 215 Terpko, M. O., 242
Svetlik, J., 203 Tamas, V., 20 Terzis, A., 212
Svoboda, J., 18 Tamura, C., 136 Tesser, G. I., 98
Swain, C. S., 378 Tamura, R., 238 Testaferri, L., 78, 149
Swaminathan, S., 18, 87 Tamura, T., 274 Testoni, G., 337
Swan, J. K., 190 Tamura, W., 261 Teuerstein, A., 389
Swank, D. W., 106 Tamura,Y., 121,139,208,256, Teupe, E. G., 288
Sweeny, J. G., 307 319 Tewari, R. S., 225
Swenton, J. S., 96, 255 Tan, S. L., 248 Teyssie, P., 191
Swern, D., 259 Tanabe, H., 369 Tezuka, H., 171
Swinbourne, F. J., 146 Tanabe, S., 183 Tezuka, T., 291
Swodenk, W., 1 Tanaka, A., 150, 21 1 Thaisrivongs, S., 284
Sycheva, T. P., 101, 102 Tanaka, H., 38,123,255,311 Thakker, D. R., 12
Sydnes, L. V., 241 Tanaka, K., 97,206 Thayer, A. L., 67
Syren, S., 218 Tanaka, M., 261 Therling, K., 260
Szabo, J., 223 Tanaka, N., 118 Thielemann, C., 110
Szabo, L., 165 Tanaka, S., 211 Thierrichter, B., 313
Szabo, T., 157 Tanaka, T., 35, 160, 266 Thind, S. S., 232
Szabo, V., 299, 309 Tanaka, Y., 147,234,261 Thio, A. P., 164
Szabo-Pusztay, K., 165 Tancioni, P., 323 Thoe, K.-W., 199
Szargan, R., 118 Taneja, S. C., 314 Thom, E., 311
Szeimies, G., 52 Tang, W.-P., 177 Thomas, D. R., 164,335
Szymanski, S., 345 Tanigawa, K., 55 Thomas, E. J., 3,57,66, 121
Taniguchi, H., 33, 148 Thomas, M. T., 339
Tabacik, V., 176 Taniguchi, M., 207 Thommen, W., 285
Tocconi, G., 167, 177 Taniguchi, Y., 151 Thompson, D. J., 378
Taddei, M., 299,347 Tanio, M., 256 Thompson, N. T., 48
Taguchi, M., 307 Tannenbaum, S. R., 94 Thomson, R. H., 249
Taguchi, Y., 18 Tanno, Y., 403 Thong, P. D., 110
Takada, K., 186,384 Tao, T.-M., 133 Thornton, D. E., 190
Takagi, Y., 229, 261 Tarburton, P., 32 Thyagarajan, B. S., 156
Takahara, M., 403 Tardella, P. A., 386 Thyagarajan, G., 190, 306
Takahashi, H., 105, 323 Tarnowski, B., 240 Tibolla, N., 307
Takahashi, K., 140, 141, 205, Tarnowski, T. L., 373, 374 Ticozzi, C., 147, 303, 346
228, 359, 408 Tarrango, G., 176 Tideswell, J., 22
Takahashi, M., 254 Tarzia, G., 267 Tiecco, M., 78, 149
Takahashi, S., 188 Tashiro, M., 140, 141, 228 Tien, H.-J., 197
Takahashi, T., 229, 366 Tasker, P. A., 364 Tietze, L.-F., 236
Takahata, H., 79 Tassi, D., 290 Tikhomirov, D. A., 34
Takahata, M., 334 Tatevosyan, A. D., 286 Tikhonov, A. Y., 257
Takaoka, A., 120 Tatsuno, T., 4 Tilak, B. D., 333
Takase, K., 155 Tawfik, A. M., 124 Tilichenko, M. N., 19, 294
Takashi, T., 53 Taylor, A. W., 74 Timberlake, J. W., 140, 370
Takashima, M., 157 Taylor, D. L., 176 Timm, U., 76, 134,135
Takayama, F., 270 Taylor, D. R., 138 Timmermann, B. N., 308
Takayama, K., 341 Taylor, E. C., 245, 263, 271 Tinapp, P., 260
Takayanagi, H.. 181 Taylor, G. F., 224, 314 Tingoli, 78, 149
Takeda, N., 25 Taylor, J. A., 102, 230 Tippe, A., 320
Takegami, Y., 168, 240 Taylor, J. B., 318 Tipping, A. E., 138
Takei, H., 122 Taylor, S. K., 385 Tishchenko, I. G., 298
Takeichi, T., 10 Tazaki, K., 109 Tisler, M., 66, 104, 180, 223,
Takeno, H., 55 Telyatnik, A. I., 379 234,256
Takeshima, T., 109 Temkin, H., 170 Titova, M. V., 91
Takeuchi, Y., 195, 221, 227, Temkovitz, P., 76 Titova, S. P., 179
239,384 Temple, D. L., 132 Tjornebo, A., 78
Takido, M., 306 Ten Bokkel Huinink, W. O., Tkac, A., 61
Takizawa, T., 165 183 Tkachenko, V. V., 155
Tajima, I., 366 Teng-Song Chen, 333 Tkachev, S. V., 187
Talbiersky, J., 9 Terasawa, T., 315 Tkatchenko, I., 21
Talbot, J. M., 104 Terashima, M., 333 T’Kint, C., 227
Taliani, L., 66, 137 Terawaki, Y , 56 Tobimatsu, T., 295
Tallent, C. R., 314 Terenin, V. I., 164, 248 Toda, F., 97
438 Author Index
Todesco, P. E., 112, 121 Trigo, G. G., 384, 386 Ugarker, B. G., 197
Toeplitz, B., 56 Trimarco, P., 195 Ulanovskaya, N. V., 202
Tohda, Y., 231,396 TrinajstiC, N., 96 Ulrich, P., 403
Tohma, E., 259 Trindle, C., 178 Ulsaker, G. A., 128
Toi, N., 395 Trivedi, H. S., 62 Umaki, N., 15
Tojo, T., 307 Trofimov, B. A., 75,280 Umano, K., 33
Tokoroyarna, T., 407 Trompenaars, W. P., 52, 350 Undheim, K., 128, 292, 302,
Tokumura, K., 12, 250 Trostrnann, U., 16, 346 328, 383
Tolbert, L. M., 164 Trotter, A. M., 269 Uneo, K., 216
Tolkunov, S. V., 99 Trozzolo, A, M., 28, 33, 192, Ung, S. N., 96
Tolmachev, A. I., 128, 133 197 Untch, K. G., 386
Tolmacheva, N. S., 182 Tsang, G. T. Y., 91 Unterhalt, B., 291
Tolstikov, G. A., 4, 91 Tsay, Y. H., 329 Unterweger, B., 153
Tomada, S., 148 Tse, A,, 231 Uppal, A. S., 127
Tomas, M., 226, 253 Tsivunin, V. S., 323 Upton, R. M., 231
Tornasi, J., 15 Ts’o, P. 0. P., 268 Urano, S., 356
Tomasson, H. P. M., 367 Tsoi, L. A., 114, 118 Urbanczyk-Lipkowska, Z . ,
Tomer, R. K., 121 Tsuboi, S., 191, 224 287
Tomiguchi, A., 79 Tsuchida, T., 25 Urbel, H., 15
Tomimatsu, Y., 128,212 Tsuchiya, T., 101, 102, 248, Urhahn, G., 61, 140
Tominga, Y., 74, 110 338, 339, 340, 341 Use, G., 214
Tomisawa, H., 386 Tsuda, Y., 332 Ushirogochi, A., 74
Tomlinson, J. P., 194 Tsugo, O., 206, 216, 224, 3.56 Usui, T., 211
Tomita, H., 307 Tsuji, A.. 209 Utagawa, T., 268
Tomita, K., 106, 188 Tsuji, J., 366 Uwera, C . , 286
Tornita, N., 259 Tsuji, K., 198 Uwimana, E., 286
Tomizawa, K., 5 Tsuji, T., 95, 150, 193 Uyehara, T., 408
Tomoda, S., 195,227,239 Tsujimoto, T., 252 Uyeo, S., 57, 334
Tomono, H., 62 Tsukayama, M., 306, 327
Toner, J. L., 373 Tsukihara, K., 137 Valters, R., 185
Topalova, 0. V., 360 Tsukuda, K., 270 Van Allan, J. A., 286, 292,
Topirceanu, M., 137 Tsuruta, T., 10, 211 306, 318
Toppet, S., 43, 116, 135, 143, Tsutsui, M., 261 Van Aswegen, J. L., 309
194 Tsutsumi, M., 147 Van Bekkum, H., 155, 384
Tori, K., 14, 57 Tu, C.-Y., 388 van Bergen, T. J., 237
Torii, S., 123 Tu, H. A,, 16 van den Ham, D. M. W., 350
Torisawa, Y., 403 Tuck, B., 155 van den Heuvel, C. J. M., 406
Torney, D. C., 247, 388 Tucker, A. C., 234 van der Gen, A., 91, 324
Torrance, J. B., 173 Tucker, H., 19 van der Kuilen, A., 271
Torre, G., 47 Tufariello, J. J., 188, 335, 382 van der Pias, H. C., 254, 268,
Torre, M., 87 Tuli, D. K., 307, 324 271, 334
Torres, D., 119 Tull, R. J., 126, 282 van der Putten, N., 382
Torres, M., 44, 134, 170, 195 Tundo, A., 163 van der Stoel, R. E., 254
Torsell, K., 187 Tung, C. C., 123 Van de Sande, C. C., 32
Toshimitsu, A., 348, 355, 404, Turchi, I. J., 245 van de Ven, L. J. M., 384
408 Turner, B. L., 283 Van Haverbeke, Y., 32
Toso, C. B., 132 Turro, N. J., 67, 399, 407 Van Heerden, F. R., 327
Toubro, N. H., 113, 192 Turuta, A. M., 28, 37 van Hummel, G. J., 350
Touzin, A. M., 285 Tyltin, A. K., 213 Van Keulen, B. J., 367
Toyoda, T., 343 Tyrrell, N. D., 57 Van Leusen, A. M., 180, 212
Toyooka, K., 137 Van Leusen, D., 180
Trainor, D. A., 91 Ucella, N., 31 Van Eendenburg, C. G. M.,
Trakhtenberg, P. L., 92 Uchida, H., 168 176
Traldi, P., 346 Uchida, T., 21 1, 231, 388 Van Eenoo, M., 21
Trammell, G. L., 316 Uda, H., 349 Van Meerssche, M., 43, 70,
Trave, R., 173 Uda, M., 138 116, 135, 145, 345
Traxler, J. T., 184 Udachin, Yu. M., 169 Van Puyveide, L., 286
Trefonas, L. M., 140 Uebel, J . J., 69 Van Rooijen, H., 285
Tremper, A. W., 53 Ueda, Y., 137 van Rooyen-Reiss, C., 382
Treppendahl, S., 280 Uemura, S., 63, 348, 355, van Royen, L. A., 402
Treskach, V. I., 112 404, 408 Van Schoor, O., 286
Tresselt, D., 326 Ueno, Y., 184 Van Tamelen, E. E., 26
Trickes, G., 134 Ueyama, M., 57 van Veldhuizen, B., 268
Trifonova, N. V., 196 Uff, B. C., 213, 248 Vane, F. M., 94, 345
A uthor Index 439
Vane, J. R., 402 Vivona, N., 198 Wasserman, H. H., 53, 146
Vandenbalck, J. L., 331 Vleggaar, R., 309 Wasylishen, R. E., 32
Vanderpool, D. P., 233 Vlems, H., 384 Watanabe, H., 89, 95, 206,
Vankar, Y. D., 27 Vlietinck, A. J., 286 297
Vanyan, Z. V., 312 Voegtle, F., 368, 369, 379, Watanabe, K., 396
Van Zyl, J. J., 327 381 Watanabe, K. A., 256
Vacca, C., 125 Vogel, D. E., 77 Watanabe, M., 48, 82, 276,
Vadasz, A., 16 Vogel, E., 360 402
Vaidya, N. K., 94 Vogel, P., 384, 404 Watanabe, N., 63
Vairamani, M., 77 Vogt, B. R., 334 Watanabe, S., 123, 254
Valch6i, M., 96 Vohra, S. K., 259 Watanabe, T., 95, 261, 262
Valenta, V., 96 Voight, H., 186 Watanabe, Y., 168, 193, 240
Valikov, P. G., 122 Volkov, M. N., 87 Watjen, F., 167
Valle, G., 44 Volkova, S. V., 118 Watson, H. A., 287
Valnot, J. Y., 7 Volodarskii, L. B., 181, 183, Watson, K. M., 215
Vaultier, M., 30, 195 257 Watson, K. N., 386
Varella, E., 194 Volpe, Y., 314 Watson, T. R., 16
Varma, A. J., 371 Vomero, S., 335 Watson, W. H., 178
Vartanyan, S. A., 102, 288, VonEina, E., 256 Watts, D. E., 8 8
368 Von Criegern, T., 71, 240 Weakley, T. J. R., 215
Vaya, J., 56, 59 von Seyerl, J., 329 Weavers, R. T., 176
Vebel, J. J., 385 Vorob'eva, E. A., 4 3 Webb, C. F., 402
Vecchio, G. L., 273 Voronkov, M. G., 85, 110, Webb, R. J., 218, 347
Vedejs, E., 91, 291, 359 32 1 Webb, R. R., 387
Vederas, J. C., 231 Voss, B., 360 Weber, B., 134, 191
Vega, E., 34 Voss, J., 69 Weber, E., 379
Vegh, V., 309 Voss, S., 173, 174 Weber, F. G., 305
Vejddek, Z., 93 Vostrikov, N. S., 4 Weber, G., 402
Venakis, T., 313, 317 V'yunov, K. A., 18 Weber, J., 95
Venkitachalam, T. V., 103 Weber, R., 108
Venturello, C., 251 Wada, F., 370 Weber, R. C., 218, 342
Venturoli, C., 129 Wade, J. J., 130, 132, 278 Weber, W. P., 62
Verani, G., 112 Wade, L. G., 317 Webster, 0. W., 370
Verbruggen, A., 143 Wade, T. N., 41, 87 Webster, R. G., 212
Vereshchagin, A. N., 14 Wagner, G., 133, 278 Weedon, A. C., 71
Verhage, M., 155 Wagner, H., 283 Weeks, P. D., 287
Verhoeven, J. J., 176 Wagner-Jauregg, T., 382 Wehrle, H., 311
Verhoeven, T. R., 5 Wahab, A., 144 Weichsel, C., 292
Verkade, J. G., 220, 409 Waigh, R. D., 250 Weider, P., 273
Verkoczy, B., 4 3 Wakabayashi, E., 390 Weikfield, R., 314
Verma, V. K., 142 Wakabayashi, T., 396 Weiler, H., 167
Vernin, G., 188 Wakefield, B. J., 102, 155, Weiler, L., 404
Vessiere, R., 37 230, 265 Weinberg, J. S., 152
Vialle, J., 205 Wakisaka, K., 55 Weinges, K., 31, 321
Viallefont, P., 218, 358 Waldman, H., 1 Weinmaier, J. H., 202
Viano, I., 325 Waldo, R. M., 192 Weinreb, S. M., 216, 224, 382
Viehe, H. G., 180 Walek, W., 111 Weinstein, B., 235
Vierling, P., 374 Walker, M. P., 398 Weinstock, L. M., 126, 282
Vietti, D. E., 176 Wall, M. E., 296 Weintraub, P. M., 324, 352
Vignudelli, E., 47 Wallis, J. D., 183, 333 Weis, C. D., 92
Vigorita, M. G., 117, 118, Walter, W., 186 Weisman, G. R., 372, 373,
345 Walton, D. J., 345 374
Viktorova, E. A., 8 4 Walton, J. C., 204 Weisshuhn, C. M., 171
Villenave, J. J., 285 Wamhoff, H., 224 Welch, S. C., 61
Vincent, C. A., 345 Wang, C.-H., 229 Welter, W., 250
Vincent, E. J., 114, 121, 125, Wang, L., 328 Wendelin, W., 386
171, 323 Wannagat, U., 330 Wender, P. A., 247, 388
Vincent, J. E., 55 Wanner, I., 402 Wendler, N. L., 231
Vincent, M., 346 Ward, D. D., 176 Wenska, G., 241
Vinuesa, L., 160 Warin, R., 191 Wentrup, C., 190, 203
Viola, F., 292, 324 Waring, P., 272 Wentrup, G.-J., 170
Vire, J. C., 331 Warning, K., 239 Wessinger, W., 163
Virmani, V., 335 Wasmuth, D., 10 Westerink, B. H. C., 94
Viswanathan, N., 252 Wasserman, A. L., 283 Westfahl, J . C., 240
440 Author Index
Westphal, G., 200 Wollenweber, E., 308 Yamashita, Y., 20, 87, 212
Wexler, A. J., 255 Wolstenholme, J. B., 378 Yamauchi, Y., 268
Whalley, D. P., 249 Wong, G. S. K., 7 1 Yamazaki, T., 53, 79, 334,
White, A. H., 24, 218, 347 Wong, J. L., 160 359
White, D. W., 220 Wong, R. Y., 315 Yamazaki, Y., 268
White, J. G., 4 9 Wong, S. C., 386 Yang Gu, T.-Y., 62
White, L. S., 407 Wood, D. E., 264 Yano, S., 90, 350
White, R. C., 135 Wood, H. C. S., 224 Yano, T., 57
White, R. S., 268 Woodgate, P. D., 114 Yano, T. Y., 239
Whitesell, J. K., 22 Woodward, M. D., 306 Yany, F., 6 8
Whiting, D. A., 328 Woolhouse, A. D:, 182 Yashima, Y., 6 4
Whittaker, R. A,, 155 Woolias, M., 161 Yashunskii, V. G., 146
Whitter, W. L., 192 Woollard, J., 333 Yasuda, A,, 22, 25
Wibmer, P., 313 Worth, B. R., 236 Yasuda, M., 383
Wichmann, K. H., 329 Wouters, S., 194 Yasuda, S., 36
Wickremage, C . , 317 Wrackmeyer, B., 77 Yasukawa, K., 306
Widdowson, D. A,, 360 Wrigglesworth, R., 224 Yasunami, M., 155
Wiebe, H. A., 43 Wright, G. E., 255 Yasuoka, N., 383
Wieser, H., 6 3 Wu, J. S., 5 3 Yates, F. S., 7 3
Wiesert, W., 316 Wu, M. T., 125, 258 Yates, J. B., 387
Wiewiorowski, M., 127 Wudl, F., 77 Yatsimirskii, K. B., 379
Wijsman, A., 324 Wulfson, N. S., 304 Yavari, I., 14
Wilbur, R. D., 8 9 Wullbrandt, D., 128 Yevich, J . P., 132
Wilcox, C. S., 284 Wunderlich, H., 345 Yoda, R., 114
Wild, J., 9 Wurthwein, E. U., 390, 391 Yogo, M., 153
Wiley, P. F., 323 Wylie, R. D., 402 Yokelson, H. B., 341
Wiley, R. H., 314 Wynberg, H., 1 0 Yokoe, I., 307
Wilhelm, E., 71 Wyrsch-Walraf, I., 149, 402 Yokoo, s., 20
Wilhelm, M., 360 Yokota, T., 160
Wilker, J. C., 386 Xiao, J. M., 328 Yokoyama, H., 8
Willcott, M. R., 385 Xicluna, A., 9 4 Yoneda, F., 224, 270
Williams, A. J., 261 Yoneda, K., 242
Williams, F. W., 6 8 Yagi, H., 12 Yoneda, N., 246
Williams, J. C., 5 3 Yagihara, M., 406 Yoneda, S., 173
Williams, J. W., 272 Yagudskii, E. B., 170 Yoshida, K., 65, 266
Wjlliamson, J., 87 Yakobson, G. G., 8 5 Yoshida, T., 408
Willmes, A., 61, 140 Yakovlev, V. I., 123 Yoshida, Z., 156, 173
Wilshire, J. F. K., 296 Yakshe, C. C., 190 Yoshidomi, M., 148
Wilson, C. E., 67 Yakubov, A. P., 80 Yoshifuji, S., 206
Wilson, D. R., 295 Yakushijin, K., 211 Yoshimura, T., 31
Wilson, E. B., 322 Yalpani, M., 224 Yoshina, S., 153
Wilson, R. M., 206, 400 Yamada, F., 248 Yoshinaga, F., 268
Wilson, S. R . 4 6 0 Yamada, K., 142, 160 Yoshioka, M., 95
Wilson, T., 67 Yamada, S., 249, 353, 406 Young, D., 21
Winkler, P., 361 Yamada, T., 8 9 Young, D. W., 244, 334
Winkler, T., 13, 240, 258 Yamada, Y., 140, 354, 405 Young, S. N., 402
Winland, M. D., 261 Yamagami, N., 89 Young, T. E., 76
Wiseman, J. R., 408 Yamaguchi, H., 270 Yousif, M. M., 206
Wiss, D. B., 294 Yamaguchi, M., 9, 365 Youzwak, H. P., 101
Wisterowicz, K., 125 Yamaguchi, R., 297 Yu, C.-C., 143
Witham, G. H., 6, 121 Yamamo, M., 342 Yudashkin, A . V., 92
Witt, W., 367 Yamamoto, A., 234, 353 Yudin, L. G., 164, 248
Witthake, P., 221 Yamamoto, I., 46, 137 Yuki, M., 35
Witty, M. J., 191 Y a m v o t o , H., 22, 25, 342 Yukimasa, H., 165
Witzke, J., 148 Yamamoto, K., 90, 150, 350 Yur'eva, V. S., 345
Wlodecki, B., 287 Yamamoto, M., 240, 275 Yus, M., 239, 260
Wobig, D., 111 Yamamoto, Y., 114, 370 Yusupov, M. M., 330
Wojciechowski, K., 8 , Yamamura, S., 17 Yutilov, Yu. M., 214
Wolf, H. R., 23, 349, 406 Yamanaka, H., 213, 230, 254
Wolf, R., 200, 201 Yamane, A., 215 Zablel, V., 178
Wolf, U., 123, 183 Yamane, K., 131 Zacharais, D. E., 259
Wolfe, S., 320 Yamaoka, H., 354 Zachner, H., 311
Wolfe-Murray, R., 205 Yamasaki, N., 407 Zagni, A,, 122
Wollard, J . , 183 Yamashima, S., 65 Zagorevskii, V. A., 152, 153
Author Index 44 3
Zaichenko, N. L., 30 Zdero, C., 305 Ziffer, H., 14, 26

Zaiken, V. G., 304 Zecchi, G., 188, 216, 217, Zikmund, J., 361
Zaitseva, G. S., 65 265, 337, 338 Ziman, S. D., 144
Zakharov, V. F., 92 Zeeck, A., 311 Zimmerman, S. B., 231
Zakhs, E. R., 283 Zefirov, N. S., 41 Zinner, G., 136, 198, 199
Zaklika, K. A., 51, 66, 67 Zehnder, M., 383 Zinner, K., 67
Zaks, I. M., 320 Zeifman, Yu. V., 60, 191, 280 Ziolkowski, J. J., 6
Zamankhan, H., 367 Zelenska, V., 122 Zlatkis, A., 32
Zamarlik, H., 223 Zelensky, I., 122 Zollo, K. A., 235
Zamboni, R., 55 Zell, R., 84 Zolotukhin, S. P., 170
Zambri, P. M., 5 Zeller, K. P., 27 Zomaya, I. I., 355
Zamkane, M., 134 Zemisova, M. N., 92 Zsuga, M., 309
Zamkova, V. V., 114 Zenchoff, G., 341 Zubairov, M. M., 408
Zamojski, A,, 63, 287 Zenner, P., 200 Zucca, M., 325
Zanardi, G., 163 Zerby, G. A,, 186 Zugravescu, I., 130
Zander, R., 200 Zetta, L., 157 Zurawel, S. J. jun., 101
Zankowska-Jasinka, W., 273 Zettl, C., 174 Zvolinskii, V. P., 92
Zarga, M. H. A., 31 Zhadnov, Yu. A., 97 Zweig, A,, 126
Zaripova, V. G., 323 Zhilina, Z. I., 345 Zyablikova, T. A., 329, 330,
Zaschke, H., 11 1 Zhukovakaya, 0. N., 155 350
Zav’yalova, V. K., 78 Zieba, U., 273 Zykova, T. V., 323
Zbaida, S., 71 Ziegler, A. E., 34
Zborovskii, Yu. L., 95 Zielinski, W., 246

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Heterocyclic Chemistry

A Review of the Literature Abstracted

The Royal Society of Chemistry

Heterocyclic chemistry. - Vol. 2 . -

All Rights Reserved

Set in Times on Linotron and printed offset by

Volume 2 of ‘Heterocyclic Chemistry’ covcrs original material abstracted from

Chapter 1 Three-Membered Ring Systems 1

Chapter 2 Four-Membered Ring Systems 51

Chapter 3 Five-Membered Ring Systems 73

Part 1 Thiophens and their Selenium and Tellurium Analogues 73

5 Thiophens Fused to Five-Membered Heteroaromatic Rings 99

Part Ii Systems containing Nitrogen and Sulphur, Selenium,

1 Introduction and Reviews 104

Physical Properties 121

Structures comprising one Five-Membered Ring and Two

15 Thiadiazoles and Selenadiazoles 134

16 Dithiazoles and Diselenazoles 141

18 Miscellaneous Ring Systems 144

Part Ill Other Five-Membered Ring Systems 145

10 Compounds containing Fused Five- and Six-Membered

11 Compounds containing Fused Five- and Seven-Membered Rings

12 Compounds containing Three or Four Fused Heterocyclic

Chapter 4 Six-Membered Ring Systems 223

Part I Systems containing Nitrogen 223

Part II Other Six-Membered Ring Systems 283

2 Heterocycles containing One Oxygen Atom 283

3 Heterocycles containing One Sulphur Atom 290

4 Fused Heterocycles containing One Oxygen or Sulphur Atom 293

5 Heterocycles containing One Oxygen and One Sulphur Atom 320

6 Heterocycles containing Two Oxygen Atoms 321

7 Heterocycles containing Two Sulphur Atoms 323

8 Heterocycles containing an Oxygen Atom

Chapter 5 Seven-Membered Ring Systems 33 1

Chapter 6 Eight-Membered and Larger Ring Systems 359

Chapter 7 Bridged Systems 381

6 Systems containing Sulphur 407

' R. P. Kayumov and T. G . Khaimova, Neftepewrab. Neftekhim (Moscow),1979, 37 and 39 (Chem.

(1) (2) (3)

Photo-oxygenation of cyclohepta-3,5-dienone that is sensitized with tetra-

Dye-sensitized oxygenation of vinylsilanes yields p -silylated allylic alcohols uia

(10) (11) (12) (13)

The kinetics of oxidation of ethene at 490-620 K, using Ag catalysts suppor-

The 1 : 1 complex formed between ZnC12 and tetramethyl-2-tetrazene reacts

25 U. M. Dzhemilev, N. S. Vostrikov, A. M. Moiseenkov, a n d G. A. Tolstikov, Izu. Akud. Nuuk SSSR,

Interest has been shown in the oxides of dicyclopentadiene, as noted earlier,'

peroxo-acids, these compounds are capable of oxygen transfer, and comprise a

Treatment of steroidal bromohydrins with ‘Ag,O’ tends to give ring-contracted

'' B. Mauze, J. Organomet. Chem., 1 9 7 9 , 1 7 0 , 265.

12--35%." A distinct advantage of this technique is that the easily recovered

(63) ( 6 5 ) R-R = (CH)4

’’ D. Z. Rogers and T. C. Bruice, J. Am. Chem. Soc., 1979, 101,4713.

The K-region phenanthrene oxide (68)undergoes photochemical ring-enlarge-

(70) (71) (72) R'R? = CH=CH

Miscellaneous Syntheses of Oxirans. Vitamin K , and a model compound, 2,3-

mechanism of the reaction is thought to involve the superoxide ion (023.A

The first isolable dichloro-oxirans have been produced by the cycloaddition of

A new method for the synthesis of perfluorinated epoxy-alkanes involves the

Spectra and Theoretical Chemistry of 0xirans.-Electrophilic additions to a

(88) (89) (90)

Two papers describe the effects of BF,.Et,O-catalysed rearrangement of

Cyclization Reactions of Oxiruns. By suitable choice of substituent and reaction

The (2)-styryloxirans (104; R' = R2 = C02Me, R3 = R4 = H),(104; R' =

A biomimetic synthesis of (*)-pallescensin A (107; R = H) has been achieved