Protecting groups for the pyrrole nitrogen atom.

The 2-chloroethyl,
2-phenylsulfonylethyl, and related moieties'
C : Z I < L ~GONZALI:~.
S
ROBI~R.I.
G I < E E N ~ I ~ UA S
ND
E .RAMON
'
TALLABS
S~i~lo.iv.
S. A . . Di\,i.\icjrrdc Ir~l~c~.s~i,ytit.icir,.
Al>tri.~crtlo
Po.srtrl 10-820. Mc;.vic,o 10. D. F., MC.vic.o
AND

S!ilrc,.v

JOSEI'II
M . MUCI-IOWSKI?
Rr.s~oi.c~lr.
Irr.srir~r~r
(!/'Oi.grriric Cl~erili.s~r:\~,
3401 Hill\,ic~~.
A~~cr~iic.
Ptrlo Al~o.CA 94304, U.S.A.

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Received October 20, 1082

CARLOS
GONZ,\L.EZ.
ROUER-IGREENIIOI!SE.
R A ~ I OTALLAUS,
N
and J O S E P ~M.
I MUCHOWSKI.
Can. J . Chern. 61, 1697 (1983).
The 7-chlorocthyl and 7-phcnylsulfonylcthyl moieties arc versatile protecting groups h r the pyrrolc nitrogen atom. 'The
2-chlorocthyl group is easily attached under phase transfer conditions using I .2-tlichlorocthanc. The 2-phenylsulfonyletl~yl
moiety is scatlily appcntlctl untlcr both phase t~xnsfcrand homogeneous solution conditions using 7-phcnylsulSonyIctl~yl
cliloritlc 5. Dcprotcction of the N-(2-chlorocthyl)pyrrolcs is accomplishcd by means of efficient thrcc-step, one-pot sequences
via the N-vinyl compounds 3 ant1 subsccl~~cnt
degradation of the N-( I-hydroxycthyl) compounds 4 or the acctoxymcrcul-ation
tlerivativcs 5 obtained thcrcfrom. The 2-phcnylsulfonylcthyl g r o ~ ~ispcxcisc(I by a rcvcrsc Michacl reaction using sodium
hydritlc or DBN as the bnsc.
The utility of the 7-chlorocthyl protccting g r o ~ ~ispcxcmplificd in a synthesis of bcnzyl cyclopcntal b]pyrsolc-5-carboxylatc
13 from I-(2-chlorocthyl)-4-c~xotctri1I1ydrt~i1doIc
2tl.
CARLOS
G~NZALE
ROBERT
Z.
GREENHOUSE.
RI\MON
TALLABS
ct JOSEPH M. MUCHOWSKI.
Can. J . Chern. 61, 1697 (1983)
Lcs unitds chloro-2 cthylc ct phdnylsulfonyl-2 dthylc sont des groupes protccteurs versatilcs pour I'atornc d'azote du pyrrole.
On attache facilement le groupe chloro-2 Cthylc, dans dcs conditions de transfert dc phase, en utilisant de dichloro-1,2 ethane.
On fixe rapidcment le groupc phtnylsulfonyl-2 dthyle dans des conditions de transfcrt de phase et en solution homogkne en
dc phdnyl~ulfonyl-2ctliylc 5. On rdalisc la ddprotcction dcs N-(chloro-2 Cthylc)pyrsolcs en trois Ctapes
utilisant lcchlor~~rc
cfficaccs dans un SCLII rdcipicnt par I'intcsmddiairc dcs coniposcs N-vinyliclucs 3 ct dc la dcgl-adation subsdqucntc dcs composCs
N-(hydroxy-l dthyl) 4 ~ L dcs
I
ddsivds d'acdtoxyrncrcuriation du cornposd 5. On Climinc Ic groupc phdnylsulfonyl-2 Cthylc au
Inoycn d'unc Idaction dc Michael inverse en utilisant l'hydsurc tlc sodium ou Ic DBN conirnc basc.
On dCmontrc I'utilitd du groupc psotcctcus chloro-2 dthylc cn synthdtisant. pour Ics besoins du laboratoirc. Ic carboxylatc-5
dc benzylcyclopenta[D]pyrrolc 13 ii partir du (chloro-2 6thylc)-l 0x0-4 tetrahydroindole 2d.
[Traduit par le journal]
In connection with synthetic studies in progress in these
laboratories, it became necessary to develop general methodology for the protection of the pyrrole nitrogen atom. This
need arose because the protecting groups currently in use are
either of limited applicability or the gcneral utility thereof is
cl a
unknown. For example. thc benzyl group has been ~ ~ s e as
pyl-role N-protector on several occasions ( I ) but sodium in
liquid ammonia is required to remove it ancl many functional
groups would not survive these conditions. The 3,4-diniethoxybenzyl moiety. scission of which is effected with 5 %
sulfi~ricacid in trifluoroacetic acid containing excess anisole, is
reported (2) to be useful for the N-protection of certain polysubstitutctl pyrroles, but no fi~rtherexan~plesof the application
of this group have been published. The benzyloxymethyl moiety (3) has considerable potential for pyrrole N-protection. It is
easily attached (benzyl chloron~ethylether/NaH) and removed
(hydrogenolysis, then aqueous base), however, its applicability
has only been demonstrated for diethyl pyrrole-3,4-dicarboxylate.'The P-(n1ethoxyethoxy)-methyl group is said ( l c.) to
serve as an N-protector, but the removal thereof has not been
described. Various acyl residues, such as acetyl ( 1 1 7 ) . benzoyl
( I / > ) , and benzenesulfonyl ( l b , 4) have been en~ployedto
'Contribution No. 628 frorn thc Syntcx Institute of Organic
Chemistry.
'Authors to whom corrcspondencc should be addrcsscd.
'An example has bccn cncountercd of the saturation of the pyrrolc
nucleus prior to the [iydroycnolysis of the bcnzyl moiety of the
protecting group (R. Grccnhousc and R. Tallabs. unpublished
observation).

block position-] in pyrroles, however. these electronwithdrawing entities drastically alter the nucleophilic character
of the heterocyclic ring system. Finally. it has recently becn
shown ( 5 ) that the readily removable (chromous acetate)
N,N-din~ethylatnino)group functions as a usefill pyrrole Nblocking moiety. Unfortunately, each pyrrole derivative thus
protected must be synthesized ~ l erlovo.
The ideal pyrrole N-protector should be inexpensive and
easy to put on and take off in the presence of a wide variety of
functional groups. It should itself be inert to a broad spectrum
of reactions and should not significantly reduce the nucleophilicity of the pyrrole system. In a previous publication frorn
these laboratories, an instance of the use of the 2-chloroethyl
moiety as a pyrrole nitrogen protecting group was described
(6). The present work reports on the optimized conditions for
the attachment and removal of that moiety as well a s the
2-phenylsulfonylethyl group. In addition, a brief account of the
2-phenylsulfinylethyl unit as a potential pyrrole N-blocking
group is given. Of the three groups, the 2-chloroethyl moiety
comes the closest to fulfilling the requirements stipulated
above.
The 2-chloroethyl unit was readily appended, in high yields
(see Table I ) to the nitrogen atom of various pyrrole derivatives
1 under phase transfer conditions using 1,2-dichloroethane as
the organic phase and reactant, with tetra-n-buty~ammoniunl
iodide as the phase transfer agent. One technique which was
devised for the cleavage of the blocking group from 2 was
based on the previous observations (6) that 2 could be dehydrochlorinated to 3 and the N-vinyl group could be removed
therefrom in a two-step sequence via the carbinolamine der-

'T,\u~lr: I. Kc;~ctiontimes. yiclds. physical const:uits of N-protected pysrolcs

Analysis

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Compo~~nd
no.

2 (1
2h
2 (,
2 tl
6 ti
6 17
6c

6 tl
8
9

R'
CHO
COC,,H,
SCH ,
-(CH,),COCHO
COC(,H,
SCH 1
-(CH,),CO-

K'
H
H
H
H
H
H

Kcaction
timc (11)

Y icltl
((21

Mclting
point
("C)

Calcd.

Found

I
I
8
2
6"
2
3''
16"
24
2

94
89
93
85
84
87
80
9I
86
88

Oil
54.5"
Oil
Oil
87-88
96.5-97
82-83
102- 103
Oil
Oil

53.34
60.8
47.85
60.70
59.30
67.23
55.49
03.34
70.53
74.24

5.12"
5.17
5.74
0. I?
4.98
5.05
5.37
5.05
5.30
5.57

5.99
7.97
7.09
5.32
4.13
4.98
4.62
4.33
4.56

53.57
66.85
47.39
0.92
59. I8
07.18
55.66
63.15
70.27
74.01

5.17
5. lh
5.75
0.24
4.90
5.34
5.32
5.59
5.31
5.04

5.89
7.78'
0.78
5.33
4.06
1.97
4.57
4.01
4.53

"Not n~i;rlysed ful- 11it1-ogcn.

"Tliis ;rlid ;dl tlic other solid C O I I I ~ O L I I were
~ ~ S crystallized f l - o ~ l ti l i c l i l o ~ ~ o ~ i i c l l ~ i ~ ~ ~ e - I l c x a ~ l c .
' I I I / P 175.0222: 177.0193 (calcd. for C,H,,,"CINS. 175.077_1:C-H,,,"CINS.177.01001.
"Preparccl fro1115 ;rnd t l i ~sodi~~~ii
si~lt01' t l i ~11yr1.01~.SCCc~})cri~ii~~itirl
SCCIIOII.
ivative 4. Thus, reaction of the chloroethyl compounds with
sodium hydride, in D M F or acetonitrile at room temperature.
produced the N-vinylpyrroles which on hydration with aqueous
hydrochloric acid" in acetonitrile provided the I-hydroxyethyl
compounds 4. These substances were converted into the deprotected pyrroles on heating with sodium acetate in aqueous
acetonitrile.' Although intermediates 3 and 4 could be isolated." it was not necessary to d o so. The yields in each step
were in excess of 90% and therefore the entire reaction sequence was routinely carried out in one pot. By this procedure
the N-(2-chloroethyl)pyrroles2cr ant1 2h were translhrmcd into
pyrrole-2 carboxaldehyde and 2-benzoylpyrrole Icr and Ih in
71% and 85% yield. respectively.
For pyrroles which did not bear a nuclc;~rdeactivating substituent, the acidic conditions required to convert the N-vinyl
conipound 3 into the carbinola~nine4 were too vigorous to
permit the survival of the pyrrole moiety. In these cases 3 was
reacted with excess mercuric acetate and the supposed acetoxy
mercury compound 5 was cleaved. in the same pot, with sodiuni borohydride. It was not determined if the borohydride reagent was, in fact, a necessary ingredient in this deprotection
er
sequence, i.e. 5 itsell' is expected to be cleaved ~ ~ n d alkaline
conditions. A specific example of the utilization of this modification of the deblocking process is described at the end of
this section (see Schenie 4). Further st~tdyof the process is
clearly in order.
The 1-(2-phenylsulfonylethyl)pyrroles6 were prepared from
2-phenylsulfonylethy1 chloride and the pyrroles by the phase
'N-vinylindoles have similar acid sensitivity (7).
'silver bcnzoatc was used for the prcviously reported cxaniplc ( 6 ) .
"For cxamplc. 3h and 41) wcrc isolatctl as oils in greater than 95%
yiclds and wcrc charactcrizcd by ir and nmr spectroscopy. Thus. the
N-vinyl compound 36 had ir (chloroform) absorptions at I645 (C=C)
and 1630 (C=O) cm I . and nmr (dcutcrioclilorofor~ii)rcsonanccs for
the olcfinic hydrogens at 6 5.1 I (dd. 2H. J ,,,,, = 0 Hz, J ,.,, = 9 Hz,
J,,. ,,,,, = 16 Hz) and 7.90 (dd. I H. J , , , = 9 hz, J ,,,,,,, = 16 Hz. partially
obscurcd by C,Hi niultiplct). Thc hydroxycthyl dcrivativc 40 sliowcd
ir (chloroform) bands at 3480 (OH). 3400 (OH), and 1605 (C=O)
cm--'.and nmr (dcutcriochlorofc~rrn)
absorptions at 6 1.75 (d. 3H. J
= 6 Hz. CH,) and - 6.3 (m.2H. CHOH). Analogous conipounds
wcrc isolatcd and rigorously charactcrizcd in the abovc nicntioncd
publication (6).

NaOAc

ACO-HgoAC

transfer technique. or from 2-phenylsulfonylethyl chloride and

the sodium salts of the pyrroles in D M F solution (see Table I ).
The removal of this blocking group was effected with sodium
in D M F
hydride or DBN ( 1,5-diazabicyclo[4.3.0]-non-5-ene)
solution at rooni temperature. Thus. pyrrole-2-carboxaldehyde
and 2-benzoylpyrrole were obtained from 6cr and 60 in
75% and 84% yield. respectively, using the sodium hydride
process .'
A brief study was made of the use of the 2-phenylsulfinylethyl unit as a pyrrole N-blocking group. For example,
1-(2-phenylsulfinylethyl)-7-benzoylpyrre 8 could be pre7Thc 7--phcnylsulfo~iylcthylgroup has rcccntly bccn uscd for the
protection of thc 3'-phosphotlicstcr function in oligodcoxyribonuclcotidc synthesis (8).

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NaH or DBN

QyPh
l o

CH2CH2CI

PhSNa

WPh
l

CH2CH2SPh

pared clirectly from 2-benzoylpyrrole and 2-phenyls~rlfinyletliy l

chloride 7. or by 111-chloroperbenzoic acid oxiclation of the
sulfide 9. Altho~rgh the sulfoxicle 8 was converted into the
N-vinyl compound 311 on heating in xylene containing excess
pyridine. the removal of the N-2-phenyls~~lfinylethyl
group was
best effected under reverse Michael conclitions using sodium
hydride as the base. Thus. the use of the 2-phenylsulfinylethyl
moiety as a means of protecting the I-position of pyrroles is at
least feasible.
Except for their sensitivity to strong bases and powerful
nucleophilcs. the susceptibility of N-(2-chloroethyl)pyn-olesto
various reaction conditions parallels that of the corresponding
N-alkylpyrroles. Thus. those N-protected pyrroles not bearing
a tleactivating substituent can be acylated (e.g. with ethyloxalyl
chloride (9)).and 2-acy lpyrroles can be rnethoxymcthylated at
C-4 in strongly acidic media (e.g., dimethoxyn~ethane/
hydrochloric acid ( I N ) in acetic acid - benzenelretlux (9)), or
reduced with sodium borohydride in methanol solution ( 50C)
to the alcohol without affecting the protecting group.' As implied by the latter reaction, the 2-chlorocthyl group is relatively
stable to n~ethanolicsodium hydroxide but nore vigorous conditions (sotliurn methoxide in t e t r a h y d r o f u r a n / m temperature (see below)) cause dehydrohalogenation to the N-vinyl
compounds. which are. however. resistant to further degradation under these conditions. Indeed, provided that the
reaction medium is basic. the N-vinyl rnoiety is also a useful
protecting group (see below). The chloro group can be displaced by powerful nucleophiles. Of particular interest is the
2 0 into the
conversion of N-(2-chloroethyl)-2-benzoylpyrrole
sulfide 9 with sodium thiophenolate. The N-(2-phenyl%. Velarde and K. Salas. unpublishcd observations

PhCH20H
Collidine

sulfenylethyl) moiety is itself a ~ ~ s c f blocking

ul
group which
has the addctl advantage that it is not s~rsceptibleto tlegraclation
by bases. It can be removed after oxiclation to the sulfoxide (see
above) or the sulfone.
The synthesis of benzyl cyclopenta[l1]pyr1ole-5-carboxylate
13 in five steps from 1-(2-chloroethy1)-4-oxotetratlydroindole
2cl is illustrative of the utility of the 2-chloroethyl protecting
group. Thus, the sodium methoxide promoted reaction of 2cl
with ethyl formate. in tetrahydrofuran solution at room ternperaturc, caused both formylation at C-6 and dehydrohalogenation of the chloroethyl moiety. 'The generation of
the N-vinyl group at this early stage in the reaction sequence

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sotliurn s~rlfatc. ancl cvapor;~tctl i r r l,oc.r~o.~l'liccr~lclc pr'oclucl was

sut?jcctccl to tlc o n silic;~gel using hcsanc - ethyl acctatc ( 9 : l ) as the
clcvclol~ingsolvcnt. .fhc pr-orluct (0. IS? g. 7 1 % . tlc liomogcncous)
was crystallizctl from tliclilorornctI~;~~ic
-1icxanc to give the nldchytlc
(0.I60 g) with mp 42-43C.
13. Corrl~,~..\iorrr!/' N - ( 2 - i ~ l r l o r ~ o c ~ t l ~ l ~ - _ 7 - I ) o 1 2r :ho ~irrto
~I~111/
? - / ) ( ' / l I O ~ / / ) > ' 1 ~ 1 ~ 0 / (1' I>
Sotlium hy(lritlc in minclxl oil (00%. 0.038 g. 0.95 11111101)was
;~tlclccl,at 50C. to a stir.rccl solution o l the c11lol.o compouncl (0.200 g.
0.80 mmol) iri tlry acetonitrile (15 m L ) maintaineel in a nitrogen
ntmosphcr-c. Aftcr 0.5 I1 at this tcnipcl.a(urc. 50% hytlrochloric acitl ( 3
n!L. 18 mmol) was atlclccl. After ;un ntltlitional 0.5 11. a solution o f
sotlium acctatc ( I .9 I g. 23 rnmol) in watcr (7.5 m L ) \r.aaclclcd ant1
the solution was hcatctl at rcl'lux ~CIIIPC~;I~LI~C 1'0s 0.25 11. .I'Iic coolcd
solution Lvas cxtractctl with clichloromcthanc. ~unclthc cstr;~ct \r.;~s
tlrictl ovcr sotlium s~rlt'ntc iuitl evaporated i r r ~.trc.rro to give
2-bcnzoylpyrrolc (0. I24 g. 85%) with mp 70-77C.
Dcl~.o/cc./io/r(!I'
rlrc N-(2-/)lrc~rr>~l.s1tl/i)11>~I(~/I1>~I
j~)>.r.~.o/o.s
A . Sotlir~rrrIr>~tl~.itlc
Sodium li!lclridc in mineral oil (OO'k, 1 . 1 ccluiv.) was ;rtlrlcrl to ;I
stirred solution of the phcnylsulk)nyl conipouncl ( I ccluiv.) in anhyclro~~s
tlimctliylhrmamidc ( 7 mL/mmol) nt room tcml,cl.aturc (nitrogcn atmosphcrc). Al'ter 2.5 h the solution was tlilutcd with ether.
the ~iiixturcW ~ I S ~;rsIictIwith water. ;111dthe orgi~riicphirsc W;IS tlriccl
over s ~ d i ~ rs~~ll'~rtc
~ i i ant1 cvaporatccl i r r ,YI~,II~.'l'hc cr~ltlcproduct was
p~rrifieclby crystallizatior) ( t l i c l ~ l o r o r n c t l ~ i ~ r ~ c - IFor
~ c 2-bcnzo!fl~i~~~c
pyrrolc) or column cliromotograpliy on silicn gel (licxanc - ctliyl
acctatc 4 : I )
2-ti)rmylpyrrolc) li)llowctl by cryst;rllization
(ether-hcxnnc: 2-tol-mylpyrrc,Ic).
B. Ilitr:ithii.>.i lo/4..l.O/rror1-5-i~rrc~
-fhc procctlurc was itlcntical to that tlcscribccl abovc except that
diuzubicyclo[4.3.OI11~)1i-.i-cnc(5-7 c c l ~ ~ i v and
.)
dictliylaminc (10
cquiv.) ucrc ~rscrl instead ol' sotli~rrii liytlritlc. In this way,
2-bcnzoylpyrrolc was obtaincil in 83% yicltl. aftcr tlc on silicn gel
using hcxanc - cthyl acctatc ( 4 : I ) ;is tlic cluting solvcnt followcd by
crystnlliz;~tion as abovc.
C o r s i o / N - - ~ l r r r l . ~ ~ l / r r / / / r / j - - 1 1 1 z 8o Iirr/o
1ol
2-hi,r1zo>~ll1>'1.1~01(~
A solution o f the sulfoxiclc 8 (0.600 g. 1.86 mmol) in anhydrous
D M F ( 5 m L ) n8asaclclccl to ;Istirrctl suspension o f OO'k sodium hyclridc
( i n mineral oil. 0.082 g. 2.05 mmoll in tlr-y D M F ( I 0 m L ) muintaincd
in an atmosphcrc o f nitrogen. After 4 I1 at room tcmpcrnt~~rc.
watcr
was adtlcd and the procluct was cstractcd into cthyl :~cctotc. 'flic
a q ~ ~ c o ~ ~ s pW
l ~;ISi r ssatur;rtcd
c
with s o c l i ~ rcliloridc
~i~
ilrid cxt~.i~ctctI
with
bcnzcnc. 7fhc cornbinctl extracts wcrc dricd ovcr sodium sulfate 2nd
cvaporntcd ill 1.trc.rro. The rcsiduc was puril'icd by tlc on silica gel using
hcxanc-ctlicr ( 2 : 3 ) as the developing solvent. .l'his proccss yicltlctl
2-bcnzoyl pyrrolc (0.290 f . 9li;7c) with mp 78C.

n stil-red solution o f 10 ( 12.7 g. 07. 1 rnmol) in clry clichloromcthanc

(100 m L ) containing tricthylaminc (14.1 S. 141 mmol) at OC. 'l'tic
mixture was stil-red at room tcrnpc~xturcfor 20 11. ~vatcr\\as atlclccl.
anel the organic phase was tlrictl and cvapor;rtccl i r r ~,oc.rro.'fhc I-csicluc
was s ~ r l ~ ~ e cto
t c tcl o l t r ~ ~clir01ii;rtogr;11>Iiy
ir~
011 IICLII~;II ;~Iu~iiili;r(500 g.
Fluka. Act I I ) nncl the 171-otluct(9.5 g. 7h'k) \\)as clutctl nit11 ctliyl
acctatc - licxnnc ( I : I ). On crystalli~;rtionI'rom ctliyl ;Icerate - hcsanc,
;I bright yellow solicl was obtainctl \\,it11 mp 84-St>"(': ~ r v200
: (0130).
341 (9190). 209 sh (0150). -370 (8830) nm: ir: 3055. 1050. 1615 cni ':
,,,,, = I . I H L . .I,,, = 9.0 Hz).
nmr 6: 3.01 (rn. 4H). 4.93 (tltl. I H . .I
5.70 (clcl. I H . .I
,,,,, = 1.1 H/. ..I
,,.,,,, = 15.0 H r ) . 0.07 (tl. I H . .I2;
=
3.1 Hz). 6.81 -7.07 (m. I H ) . 6.99 (d, l H . J1, = 3.1 Hz). E.vtr(.~Mo.\.v
(high resolution mass spectrum) c;llcd. for C,,,Hc,N30: 187.0746:
huncl (ma): 187.0749.

N(,II:>,/ I - ~ ~ i r ! \ ~ l ( : \ . c ~ l o ~ ) ( ~ ~r r t~( r~l l ~ ~ I ~ I ~ ~ I ~ ~ 12

- . ~ - ~ ~ ~ I I ~ I I ~ . ~
A solution o f the tliaro compouncl (3.47 g. 17.6 mmol) in collitlinc
( I 5 11iL)cor~t;~irirr~g
bcrizyl irlcoliol ( 0 111L)W;IS Iic;~tcd in i r r i oil hilt11
rn;~int;~rnctlat 175C 1'01- 20 ri~irl..fhc coolctl soltrtiori W~IS tlil~rtctlwith
ether. \vaslictl with I N hytlrochloric acitl. tlriccl. ant1 cvaporntcd i r r
1.crc.oo. l'lic rcsicluc was sul-rjcctccl to column chromatography on silic;~
gel usin2 hcxanc - cthyl ucctatc ( 7 : 3 ) to clutc tlic oily. somewhat
~~ristablc
protluct ( 1 .93 g. 41%): LIV: 217 (13 700). 248 (14 600) nm:
ir: 1734. 1651 clii I ; 111111.6: 2.79-3.07 (111. 2H). 3.90 (m. I H ) . 4.62
(dcl. I H . J ,.,,, = 1.3 Hz. J,,, = 9.7 Hz). 5.03 (tltl, 1H.J ,,,,, = 1.3 Hz.
J ,,,,,,, = 15.3 Hz). 5.71 ( 5 . 2H).(7.14(tl, IH..12, = 3 . 0 H z ) . (7.70(clcl.
2H..I,,.= 9.7Hz..l,,,,,,, = 15.3Hz),O.X5(d. IH,.12,; = 3.0Hz).7.43
(s. 5H): mass spectrum rrr/(, 207 ( M - ) . Arrctl. calccl. for C17H17N0,:
C 76.38. H 6.4 1 . N 5.24; I'ountl: C 75.92. H 0.53. N 5. I I .
Urrr_\.l c ~ ~ ~ c ~ l o / 1 r r r ~ o / 1 ~ / 1 ) ~ ~ 1 ' 1 ~ o I o13
-5-~~~11~I)o.vlir/
A solution o f the N-vinyl compound 12 ( 1 .OO g. 37.5 mmol) in
accronitrilc (25 m L ) was adtlccl to a solution OF mercuric occtatc (3.7
g, 106 rnmol) in 10'k aqueous ucctonitrilc (25 m L ) zuncl tlic solution
was stirred at room tcmpc~-i~tul.c
until the reaction was complete by tlc
(0.5 h ) . Sotlium borohyrlrirlc (0.57 y ) \vas then adtlccl in portions iuncl.
when the vigorous reaction h;rd suhsiclccl. the mixture Lvas filtcrctl
through Cclitc. .l'lic filtrate was tlilutctl \\.it11 s;rturatctl soclium cliloridc
solution and cxtractctl with cthyl acctatc. 'l'hc cstr;~ct \\as clrictl. the
solvcr~tW;IS r c ~ i ~ o v ei r d
r \,(ri.l(o. ;II~LI
tlic rcsitluc \\.;is pcrcolirtcd tliro~rgli
;I short column o f silica gel 115inghcxanc - ctliyl acctatc as the pcrc o l i ~ t i ~sl g
o l v c ~ r~iixt~rrc.
~t
~I'IicI>~OCILIC~
(0.593 g. 60%) wits o b t i i i ~ i ~i l Sd
;In oil; ~ r v 217
:
(8910). 241 (5750). 200 (457). 268 (309) nm: ir: 3515,
3420, 1733 ern '; nmr 6 : 2.78 (m, 4H). 3.77-4.09 (m,I H ) . 5.18 ( s .
2H). 6.06 (d (aftcr D 2 0 exchange). I H . J = 2.8 Hz), 6.69 (d (aftcr
D 2 0 cxclinngc). I H . J = 2.8 Hz). 7.41 (s. 5H). Arrol. calccl. for
CliH15N02: C 74.67. H 0.27. N 5.81: I'OLIII~: C 74.99. H 6.36.
N 5.67.

I . ((I) S. U-\KONI.I<.S,~RI\I)I. ;111el M. J. S:\(.C.~\RELL~.

J. Hctcrocvcl. Clicm. 17. 1221 (1980); ( b ) W . A. R[<all-t<s,R. H . Rtrrf-I.
G. J. GIUBS. :uitl M . J. Wtllss. J. Org. Clicm. 36, 1232 (1971);
I-Virr!,l-4-o.vo-./..i, 6 , 7 - ~ c ~ 1 ~ c r l r ~ t l 1 ~ o i 1 r ~ I o I ~ ~ - 4 - ~I0~ i r , ~ l ~ o . v r / i / i / 1 / i
36. 1241 (1971): ((.) D. P. Scttu\t.\ctrr:.~iuidS. S. HALL. J. Org.
A solution of'thc chloro compound 2 t l (14.2 g. 71 .X rnrnol) in clry
Chcm. 46. 5060 ( I98 I ) .
tctraliytlrofuran (40 m L ) was atitlctl to a stirrc(l suspension of sodium
2. M . I. JoNrrs. C. Fnoussots. ant1 D. A . E\~,\Ns..J. Chc~ii.SOC.
mctlioxitlc ( 1.5.5 2. 290 mmol) in anhydrous tctl-;~hyrlrof~rlm
( 100 m L )
Chcrn. Comm~rn.472 (1976).
containing anhytlrous cthyl forrnntc (21.5 g. 290 mmol). Aftcr ? I1 at
3. H . J. ASI)ERSON and J. K . Gtto\lt;S. Tctrahctlron Lctt. 3165
room tcmpc~xturc,watcr was atldctl arrtl the solution was acidified to
(1971).
pH 4 with 1 M hydrochloric acid. rflic product was cxtr;~ctcdinto cthyl
4. R. X . X u . H . J. AN1)ERSON. N. J. Go(;AN. C. E. Lot\f)EI<, ant1
acctatc. and the extract was dricd ovcr sorli~rm\ulfatc ant1 cvnporntcd
R. MCDONI\LL). Tctrahctlron Lctt. 22. 4899 ( 198 1 ); J. K o t i ~ c t t .
ill ~,oc.rro.The solid which remained was cryst;~llizcdI'rorn cthyl accP. HAMEL.M . KAKUS~II~I!\.
ant1 G . M . S L I I ' ~ ~.l'ctr;lhctlron
~.
Lctt.
tatc - hcxanc to give mntcrinl ( 12.7 g. 9 3 8 ) \\lit11 mp 98.5- 100C: LIV:
22. 4901 (1981).
239 (14 500). 274 (12 600). 322 sh (5OlO) om; ir: 1641. I585 ern I ;
5. G. R. Ml\lcrlNEz. P. A . G n t ~ c o ant1
,
C. V . SRINIV,\SAN.J . Org.
nrnr fi: 2.72 (m.4H). 4.95 (d. I H , J,,, = 9.0 Hz). 5.28 (tl. I H . J,,,,,,,
Chcm. 46. 3760 ( 1981 1.
= 15.4 Hz). 6.68 ((1. I H <
,2
.I.
= .3.l Hz). 6.86-7.25 (m.I H ) . 7.06
6. J. ACKRELL.. F. FR:\NCO, I<. GREENIIOUSE.A. GUZLI~~N.
and
(d. I H . J2, = 3.1 Hz). 7.32 (s. I H ) . Arrtrl. calctl. for CIIHIINOZ: C
J. M . M c c t l o \ v s ~ t .J. Hctcrcocycl. Chcm. 17. I08 I (1980).
09.83. H 5.86. N 7.40: found: C 69.56. H 5.94. N 7.47.
7. E. S. D~IIINA. N . P. GL,\zKOV,\. G. G. SK\I~I<TSO\/,\.ancl M. F.
SHOSI',\K~VSKII.Khirii. Atsctilcria. 203 (1968): Chcm Abstr. 71.
I-Virr~~l-4-o.ro-5-tlit1:o-4,5,6,7-/c/r-t~lr~tlroi11tIoI~~
11
(31 l?Ob (1969).
A susl)c~~sion
oF2.4.6-triisopropylbcnzcncsull'onylnzidc (15) (22.8
8. M . U,\~c;ont~.S. J~SEI~~ISON,
and J. U. CH,\.ITO~>,\~)IIY,\Y~\.
Tctg, 73.8 mmol) in anhydrous tlichloromcthanc (40 m L ) was added to

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rahctlron Lctt. 22. 1915 (1981)

9. H. C : \ I < I ~ E.
I ~ . G!\l.r:nzz~. K . Gnti~utlo~st:..A. GLI%\I!\N.
E.
VEI.!\RI)E. Y . A K I - 0 ~ 1 0A.. L I O N .V. ~'EI<l3%, K. S:\I.:\S. [I.
VALI)LS.J . ACKREI.1.. D. CtlO. P. G:\I.~.I:(~I<:\.0. H;\I.IJEKN.
k.
KOE~.ILEK.
M . L. M.\I)r)os. J . M. ML:C'IIO\\'SKI.
A. P I < I N C E
D..
l'~:cic;. T. C. I'IILKLI!:R.
A. R. V..\s HORN,wit1 D. W R E N C
. ~ u iJ. .
Clicm. 60. 2295 ( I 9 S 2 ) .
10. J . Wt11.r~and G. MCGILI-IVR,\Y.
J . Or:. Clicm. 42. 4248 ( 1977).
I I. F. Fr<,\wco. K. G R ~ : I ~ N ~ ~ C;111cl
I L ; JS. LM
. . ~ I U C ' ~ I O \ \ :JS. KOr:.
I.
Clicm. 47, 1682 (1952).

12. J . M . Uol3al.r. C. L. Kc:l.~,\nsl. C. P. Dcrl':\. H. Kot;or). nncl

K . M . C I I I O N CJ .; .01.:. Clic~ii.43. 3541 (1978).
13. A. H. FoR1)-h4001<1<.K. A. PlTfEl<S. ;111il K. W. WAKI:I.IN.J .
Clicm. Soc. 1754 (1949).
14. F. G . U~RI)\\'L:~.I.alici W. T. BK:\NNEN.
J . Am. Chcm. Soc. 86.
4045 ( I 964).
15. R. E. HARMON.
G. WELLMAN,
and S . K. GUPTA.J . Org. Cticni.
38. 1 1 (1973).