N S O
Heterocyclic Chemistry
Heterocyclic Chemistry
1)
The common nomenclature: which convey little or no structural information but it still widely used. The Hantzsch-Widman (IUPAC or Systematic) method which in contrast is designed so that one may deduce from it the structure of the compound. The replacement method
2)
3)
Heterocyclic Chemistry
I-Common Nomenclature
Each compound is given the corresponding trivial name (which should be memorized, see the following slides). This usually originates from the compounds occurrence, its first preparation or its special properties.
If there is more than one hetroatom of the same type numbering starts at the saturated one, e.g. imidazole.
4
N3
2 1
N H
If there is more than one type of the heteroatoms, the ring is numbered starting at the hetroatom of the higher priority (O>S>N) and it continues in the direction to give the other hetroatoms the lower numbers as possible.
Heterocyclic Chemistry
Common Nomenclature
If subsituents present, their position should be identified by the number of the atoms bearing them and then they Br should be listed in alphabetical order.
4
3 1 O
N
5
H2N
5-Amino-4-bromoisoxazole
three or four atoms are saturated. These words are preceded by numbers indicate the position of saturated atoms as low as possible and followed by the corresponding fully unsaturated trivial name.
H N
1,2-Dihydro-pyridine
Heterocyclic Chemistry
Trivial names
1) 5-membered heterocycles with one or two heteroatoms
Pyridazine
Heterocyclic Chemistry
Trivial Names
3) Fused heterocycles
O N N N NH NH2
Guanine
Heterocyclic Chemistry
Trivial Names
O O
O Chromen-4-one
O Flavone
Ph
Coumarine Chromen-2-one
6 7
8 4 3 2 7 6 5 1
1 2
9 N
H
10 N 4
H
9,10-Dihydro-acridine 9H-Carbazole
Heterocyclic Chemistry
Trivial Names
4) Saturated heterocycles
Exercise :
Give the common name of the following compounds:
N O H N
H2N
CH3
Heterocyclic Chemistry
NH
II-Replacement nomenclature
In replacement nomenclature, the heterocycles name is composed of the corresponding carbocycles name and an elemental prefix for the heteroatom introduced (if more than one heteroatom is present they should be listed according to the priority order shown in (table 1). According to this nomenclature, tetrahydrofuran, for instance, is called oxacyclopentane.
Table 1
Atom
O
Se
Prefix
oxa
selena
Priority decreases
thia
N P
aza
phospha
Heterocyclic Chemistry
Benzene
N
1,4-Diazabenzene
Cyclopentadiene
O N
Oxacyclopenta-2,4-diene
Cyclopentadiene Cyclopropane
O
1-Oxa-3-azacyclopenta-2,4-diene
O
Oxacyclopropane
N O
Cyclopropene
Oxazacyclopropene
Cyclopentadiene
S
1-Thia-2-azacyclopenta-2,4-diene
Cyclohexane
1-Oxa-4-azacyclohexane
N H
Naphthalene
N
2-Azanaphthalene
Heterocyclic Chemistry
cyclohexane
S
8 7 6 5
Thiacyclohexane
8a
1 2
naphthalene
N
4a 4
2 3
4a
3 4
4H-4a-azanaphthalene
naphthalene
S
2 1
1,4-dithianaphthalene
cyclododecadiene
N O O N
7 8
1,7-Dioxa-2,8-diazacyclododeca-2,8-diene
Heterocyclic Chemistry
Hantzsch-Widman rules for fully saturated and fully unsaturated heterocycles 1) Identify the hetroatom present in the ring and choose from (table 1 on slide 9) the corresponding prefix (e.g. thia for sulfur, aza for nitrogen and oxa for oxygen). 2) The position of a single heteroatom control the numbering in a monocyclic compound. The heteroatom is always assigned position 1 and if substituents present are then counted around the ring in a manner so as to take the lowest possible numbers. For example:
4
N1
2
CH3
Heterocyclic Chemistry
Hantzsch-Widman rules
3) A multiplicative prefix (di, tri, ect.) and locants are used when two or more similar heteroatoms contained in the ring( two nitrogen indicated by diaza) and the numbering preferably commenced at a saturated rather than an unsaturated atom, as depicted in the following 4 example: 1,3-diaza. N3
5 1 2
4) If more than one type of hetroatoms present in the ring the name will include more than one prefix with locants to indicate the relative position of the heteroatoms. Atom prefixes have a strict order of priority (preference) in which they are to be listed. For example,Oxa(for oxygen) always comes before aza (for nitrogen) in a name (see table 1). When combining the prefixes (e.g. oxa and aza) two vowels may end up together, therefore the vowel on the end of the first part should be omitted (oxaza).
Heterocyclic Chemistry
N H
Hantzsch-Widman rules
The numbering is started from the heteroatom of the highest priority in such a way so as to give the smallest possible numbers to the other heteroatoms in the ring (the substituents are irrelevant). For example the prefix corresponding to the following compound is 4-Methyl-1,3Thiaza.
4
N3
2 1
5)
Choose the appropriate suffix from (table 2) depending on whether or not nitrogen atom is present in the ring, the size of the ring and presence or absence of any double bonds Combine the prefix(s) and suffix together and drop the first vowel if two vowels came together.
Heterocyclic Chemistry
6)
Hantzsch-Widman rules
Table 2
Ring size N-present N-absent
sat
iridine etidine olidine
a a
sat
irane
etane
olane ane epane ocane
a a
onin
ecin
onane ecane
Heterocyclic Chemistry a: means use the prefix perhydro followed by the fully
Hantzsch-Widman rules
Examples
H N
This ring contains (N) Prefix is aza The ring is 3-membered and fully saturated suffix is iridine By combining the prefix and suffix, two vowels ended up together (azairidine), therefore the vowel on the end of the first part should be dropped. This gives the correct name: Aziridine
Heterocyclic Chemistry
Hantzsch-Widman rules
HN O
This ring contains (O ,N) and (o) has higher priority than (N) and by starting numbering the ring at (O) Prefix is 1,2-Oxaaza, but the first vowel must be omitted to give 1,2-Oxaza The ring is 4-membered and fully saturated suffix is etidine By combining the prefix and suffix, two vowels ended up together (1,2-oaxazaetidine), therefore the vowel on the end of the first part should be dropped. This gives the correct name: Heterocyclic Chemistry 1,2-oxazetidine
Hantzsch-Widman rules
4 3
N O
1
N2
This ring contains (O) prfix1 (oxa), and two (N) prfix2 diaza Locants, since (O) is higher priority than (N) so it is in position 1 by default and the two (N) are therefore at positions 2 and 5, this gives the combined prefixes as 1,2,5-oxadiaza (note that the a in oxa is not dropped) It is 5-membered,fully unsaturated ring with (N) the suffix is ole By combining the prefixes and the suffix and dropping the appropriate vowels we get the correct name as 1,2,5-Oxadiazole
Heterocyclic Chemistry
Hantzsch-Widman rules
N H
The ring is 6-memberd, fully saturated with N Prefix perhydro followed by the name of fully unsaturated 6memberd ring with nitrogen azine Thus the full name is perhydroazine
Heterocyclic Chemistry
Hantzsch-Widman rules
Exercise:
Explain how can you name the following heterocycles.
Br N O O S N N N S
Heterocyclic Chemistry
a)
Partial unsaturation in heterocyclic compounds can be indicated by one of the following methods: The position of nitrogen or carbon atoms which bear extra hydrogen atoms must be indicated by numbers and italic capital H (e.g. 1H, 2H, etc.) followed by the name of maximally unsaturated ring.
4 5 6 1 O 3 2
4 5 O 1
3 2
1 N H 1H-Azepine
3N 4 2S 1 5 O 5H-1,2,3-Oxathiazole
2H, 3H-Oxole
4H-Oxin
Heterocyclic Chemistry
N H
N H
1,2-Dihydroazine
1,4-Dihydroazine
2,3,4,5-Tetrahydroazine
2,3-Dihydrooxole
Isomers have the same M.F. but differ in the position of the double bond
Heterocyclic Chemistry
-etine -oline
-etene
-olene
Heterocyclic Chemistry
HN
HN
O
2
5 1
5 1
-Azetine
-Oxetene
3
N H
-Azoline
4 3
2 -Oxolene
NH
2 1 5
2 1
-1,3-Thiazoline
N H
2 -1,3-Diazoline
Heterocyclic Chemistry
Naphthalene
Ortho-and peri-fused rings: are those found in a polycyclic compound with a ring that is ortho- fused to different sides of two other rings that are themselves ortho-fused together (i.e. there are three common atoms between the first ring and the other two).
Heterocyclic Chemistry
1H-Phenalene
or fused heterocylic system fused to benzene are known benzoheterocycles. Also bicyclic compounds with two fused heterocyclic rings are well known. Both types can be named according to certain rules
Heterocyclic Chemistry
Unless listed as a trivially named heterobicycle (see slide 6), a benzene ring fused to a heteromonocycle of five or more members or a heterobicylcle is named by prefixing the word benzo to a letter indicating the position of fusion in square brackets by the name of heterocyclic ring (common or IUPAC or modified replacement name). Name= Benzo[letter]name of heterocyclic ring For designating the position of fusion, the peripheral bonds of the heterocyclic ring are consecutively assigned alphabetical letters staring with the 1,2-bond as a side and the labeling is continued around the ring to give the common bond the lowest order.
Heterocyclic Chemistry
a O b
5
3 4
c d
a
S
1
b a
2
5 1
5 7 6
N H
Benzo[b]furan
Benzo[d]thiepine
Benzo[b]pyrrole Indole
b
2
f
1 6
4 4a
d a
c
3
b c
a
S
5 1
N
7 1 8a 8
b
2
Benzo[b]pyidine Qunioline
Benzo[f]qunioline
Benzo[c]thiophene
Heterocyclic Chemistry
N O
5 3 4
c
2 1 3
Chromeno[2,3-c]pyrrole
Heterocyclic Chemistry
O
2
7 6
S
4
a
2 3
2 1
Substituent ring Thiopyrano with one satrated C that take locant 7 when the system is numbered as a whole (starting from O to give the two heteroatoms locants 1,4 while starting from S gives them locants 1,5)
7H-Thiopyrano[3,2-b]furan
Heterocyclic Chemistry
I-Nomenclature of Fused Heterocyles Rule 2: A heterocyclic component containing the largest possible individual ring
O 1
Indicated H
b a
O
2 3
2H-Furo[3,2-b]pyran (pyran [6] preferred to furan [5]) Numbering the whole system is started from O in furan ring to give the two heteroatoms locants 1,4 while starting from O in pyran ring gives them locants 1,5, thus the indicated H takes locant 2
Heterocyclic Chemistry
Rule 3: A heterocyclic component containing the greater number of hetroatoms of any kind
8 7N 1 8a
b c a d
5
2 3
4a
N 1
6 O
3 4
N.B. The whole molecule is numbered starting from pyridine ring to give the three heteratoms the lowest locants (1,6,7), however, stating from oxazine ring will give them locants (2,3,5) or (2,3,8).
Heterocyclic Chemistry
NOMENCLATURE OF FUSED HETEROCYCLES Rule 4: A heterocyclic component containing the greater variety of hetroatoms
a b
O
d c
3
4 5
NH
1N
N.B. The whole molecule is numbered starting from pyrazole ring to give the four heteratoms the lowest locants (1,2,4,6). While starting from oxazole ring give them locants (1,3,4,5) or (1,3,5,6).
Heterocyclic Chemistry
NOMENCLATURE OF FUSED HETEROCYCLES Rule 5: A heterocyclic component containing the greater number of heteroatoms most preferred when considered in order F, Cl, Br, I, O, S, Se, Te, N, P, As, Sb, Bi, Si, Ge, Sn Pb, B, Hg
S N c
5
1 4 2
b a
O
Heterocyclic Chemistry
NOMENCLATURE OF FUSED HETEROCYCLES Rule 6: A heterocyclic component with the lower locants for heteroatoms
b
N
c
2
N
1
a
N
N H Heterocyclic Chemistry
NOMENCLATURE OF FUSED HETEROCYCLES Rule 7: If a position of fusion is occupied by a heteroatom the name of the component rings to be used are so chosen as both to contain the heteroatom.
S N 3
2 1
a b
N
Imidazo[2,1-b]thiazole
Heterocyclic Chemistry
a)
4 2 5
O
H3 N
2
N
3 2
O
H N N
4 5
6 1H-Furo[2,3-d]imidazole
b)
1
O
5 4
4 6 2
Not 7
5 3 3
Not
8
N
5
N
4
N
6 7
N
2
N
4a
8a
2
N
8a
d)
6
N O
4
N
3
O
4N
H
2
O
Not
N H
6
2H,4H-[1,3]dioxol[4,5-d]imidazole Indicated hydrogens 2,4 not 2,6
Heterocyclic Chemistry
NOMENCLATURE OF HETEROCYCLES
Exercise Q1. Name the following compounds (a-d):
N S N N H N N O S
(a)
(b)
(c)
(d)
Heterocyclic Chemistry
Heterocyclic Chemistry