Nomenclature of

Heterocyclic Compounds

Dr. Solomon Derese SCH 402 13

The IUPAC rules allow three nomenclatures.

I. The Hantzsch-Widman Nomenclature.

II. Common Names

III. The Replacement Nomenclature

Dr. Solomon Derese SCH 402 14

I. Hantzsch-Widman Nomenclature

n = 1,2,3, ……

The Hantzsch-Widman nomenclature is based on

the type (Z) of the heteroatom; the ring size (n) and
nature of the ring, whether it is saturated or
unsaturated .
This system of nomenclature applies to monocyclic
three-to-ten-membered ring heterocycles.
Dr. Solomon Derese SCH 402 15
I. Type of the heteroatom
The type of heteroatom is indicated by a
prefix as shown below for common
hetreroatoms:
Hetreroatom Prefix
O Oxa
N Aza
S Thia
P Phospha

Dr. Solomon Derese SCH 402 16

II. Ring size (n)
The ring size is indicated by a suffix according to
Table I below. Some of the syllables are derived from
Latin numerals, namely ir from tri, et from tetra, ep
from hepta, oc from octa, on from nona, ec from
deca.
Table I: Stems to indicate the ring size of
heterocycles
Ring size Suffix Ring size Suffix
3 ir 7 ep
4 et 8 oc
5 ol 9 on
6
Dr. Solomon Derese in SCH 40210 ec 17
The endings indicate the size and degree of
unsaturation of the ring.

Table II: Stems to indicate the ring size and degree of

unsaturation of heterocycles
Ring size Saturated Unsaturated Saturated (With Nitrogen)
3 -irane -irine -iridine
4 -etane -ete -etidine
5 -olane -ole -olidine
6 -inane -ine
7 -epane -epine
8 -ocane -ocine
9 -onane -onine
10 -ecane -ecine
Dr. Solomon Derese SCH 402 18
According to this system heterocyles are named by
combining appropriate prefix/prefixes with a stem
from Table II. The letter “a” in the prefix is omitted
where necessary.
Each suffix consists of a ring size root and an
ending intended to designate the degree of
unsaturation in the ring.
It is important to recognize that the saturated
suffix applies only to completely saturated ring
systems, and the unsaturated suffix applies to
rings incorporating the maximum number of non-
cumulated double bonds.
Dr. Solomon Derese SCH 402 19
Systems having a lesser degree of
unsaturation require an appropriate prefix,
such as "dihydro"or "tetrahydro".

Saturated 3, 4 & 5-membered nitrogen

heterocycles should use respectively the
traditional "iridine", "etidine" & "olidine"
suffix.

Dr. Solomon Derese SCH 402 20

 Examples

Oxa+irane= Oxirane Thia+irane= Thiirane Aza+iridine= Aziridine

Oxa+etane=Oxetane Thia+etane=Thietane Aza+etidine=Azetidine

Oxa+olane= Oxolane Thia+olane= Thiolane Aza+olidine= Azolidine

Dr. Solomon Derese SCH 402 21

 Azinane Azine

Pyridine

Dr. Solomon Derese SCH 402 22

In case of substituents, the heteroatom is
designated number 1, and the substituents around
the chain are numbered so as to have the lowest
number for the substituents.

Dr. Solomon Derese SCH 402 23

The compound with the maximum number of
noncumulative double bonds is regarded as
the parent compound of the monocyclic
systems of a given ring size.

Dr. Solomon Derese SCH 402 24

Partial Unsaturation
Use fully unsaturated name with dihydro, tetrahydro,
etc
3
2
1
HN
Azepine 2,3-Dihydroazepine

4,5-Dihydroazepine 2,5-Dihydroazepine
Dr. Solomon Derese SCH 402 25
When numbering give priority to saturated atoms.

1-Ethyl-4-methyl-4,5-dihydroazepine
N

1-Ethyl-5-methyl-2,3,4,5-tetrahydroazepine
N

Dr. Solomon Derese SCH 402 26

Revision
Hetreroatom Prefix
Type (Z) - Prefix O Oxa
Size (n) - Suffix N Aza
Nature of ring - Ending S Thia
P Phospha
Ring size Saturated Unsaturated Saturated (With Nitrogen)
3 -irane -irine -iridine
4 -etane -ete -etidine
5 -olane -ole -olidine
6 -inane -ine
7 -epane -epine
8 -ocane -ocine
9 -onane -onine
10 -ecane
Dr. Solomon Derese -ecine SCH 402 27
Rings With More Than One Heteroatom

Dr. Solomon Derese SCH 402 28

Two or more similar atoms contained in a ring are
indicated by the prefixes ‘di-’, ‘tri’, etc.

1,3,5-Triazine
If more than one hetero atom occur in the ring,
then the heterocycle is named by combining the
appropriate prefixes with the ending in Table I in
order of their preference, O > S > N.
Dr. Solomon Derese SCH 402 29
 1,3-Thiazole
Oxaziridine
(Thiazole)

1,4-Oxazine 3-chloro-5-methyl-1,2,4-oxadiazole
Dr. Solomon Derese SCH 402 30
Priority of heteroatoms for numbering purposes:

Highest

B C N O
Lowest P S
Se

Dr. Solomon Derese SCH 402 31

The ring is numbered from the atom of
preference in such a way so as to give the
smallest possible number to the other hetero
atoms in the ring. As a result the position of
the substituent plays no part in determining
how the ring is numbered in such
compounds.

4-Methyl-1,3-thiazole

Dr. Solomon Derese SCH 402 32

II. Common Names
There are a large number of important ring
systems which are named widely known with
their non-systematic or common names.

H
O N

Furan Pyrrole
Dr. Solomon Derese SCH 402 33
 N
O O
Isoquinoline Coumarin

Dr. Solomon Derese SCH 402 34

 1,4-Dihydropyridine 2,3-Dihydropyridine

Dr. Solomon Derese SCH 402 35

Identical systems connected by a single bond
Such compounds are defined by the prefixes bi-, tert-
, quater-, etc., according to the number of systems,
and the bonding is indicated as follows:

1 1

2’ 2’
2 4’
2 3’’ 1’’
1’ 2’’
1’
2,2' - Bipyridine 2,2': 4',3'' - Terthiophene
Dr. Solomon Derese SCH 402 36
 Naming Hetrocycles with fused rings
When naming such compounds the side of the
heterocyclic ring is labeled by the letters a, b, c, etc.,
starting from the atom numbered 1. Therefore side
‘a’ being between atoms 1 and 2, side ‘b’ between
atoms 2 and 3, and so on as shown below for
pyridine.
c d
b e
a f
Dr. Solomon Derese SCH 402 37
The name of the heterocyclic ring is chosen as
the parent compound and the name of the
fused ring is attached as a prefix. The prefix in
such names has the ending ‘o’, i.e., benzo,
naphtho and so on.

b b c
a
a a b
Benzo [b] furan Benzo [c] thiophene
Benzo [b] pyridine
Dr. Solomon Derese SCH 402 38
 d Benzo [d] thiepine
a
c
b

Dr. Solomon Derese SCH 402 39

In a heterocyclic ring, other things being equal,
numbering preferably commences at a saturated
rather than at an unsaturated hetero atom.

1 2 1
HN N N

N2

3-Ethyl-5-methylpyrazole 1-Methylindazole

Dr. Solomon Derese SCH 402 40

 Handling the “Extra Hydrogen”

Dr. Solomon Derese SCH 402 41

Heterocycles with maximum number of double bonds
which can be arranged in more than one way.
Examples

Pyrans
Double bonds Double bonds
@ 2 and 4 @ 2 and 5

Double bonds Double bonds

@ 2 and 4 @ 1 and 3
Pyrroles
Double bonds
@ 1 and 4

Therefore, should have different names.

Dr. Solomon Derese SCH 402 42
This is a special problem resulting from isomerism in the
position of the double bonds which is sometimes referred
to as “extra-hydrogen” and this can be addressed by
simply adding a prefix that indicates the number of the
ring atom that possesses the hydrogen using italic capital
‘1H’ ‘2H’ ‘3H’, etc. The numerals indicate the position of
these atoms having the extra hydrogen atom.
4
2 3

1 1 2
2H-Pyran
4H-Pyran
The saturated position takes priority in numbering.
Dr. Solomon Derese SCH 402 43
 1H-Pyrrole 3H-Pyrrole 2H-Pyrrole
(Pyrrole)

2 4 3
3
1 2
1 4

4-Methyl-2H-oxete 2-Methyl-2H-oxete
Dr. Solomon Derese SCH 402 44
Dr. Solomon Derese SCH 402 45
III. The Replacement Nomenclature
In replacement nomenclature, the
heterocycle's name is composed of the
carbocycle's name and a prefix that denotes
the heteroatom.
Thus, "aza", "oxa", and "thia" are prefixes for a
nitrogen ring atom, an oxygen ring atom, and a
sulfur ring atom, respectively.
Notice that heterocyclic rings are numbered so
that the heteroatom has the lowest possible
number.
Dr. Solomon Derese SCH 402 46
 NH N

2-Methylazacyclohexane
or N-Ethylazacyclopentane
2-Methylpiperidine or
N-Ethylpyrrolidine
Dr. Solomon Derese SCH 402 47
Dr. Solomon Derese SCH 402 48
 Gattermann Kotch reaction
Step 1:

Step 2:

Step 3:
Consult The Slides (18-42) in Furan reactions
part 2 for the following reactions.
• Gattermann-Koch Reaction mechanism
• Vilsmeier Reaction
• Houben Hoesch Acylation
• Mannich Reaction
Thiophene can be prepared by passing a mixture of
ethyne and hydrogen sulphide over alumina at 400oC
Gewald Synthesis
• Gewald Aminothiophene Synthesis
• This method was reported by Gewald in 1966. Gewald synthesis is the
usual route to 2-aminothiophenes.
• It consists of the base-catalyzed condensation of a ketone having a
CH2 group with a β-ketonitrile to form an olefin, followed by
cyclisation with elemental sulfur.
Mechanism
 Pyridine
Six membered heterocyclic
compounds
http://webpages.iust.ac.ir/naimi/Lectures/Heterocyclic%20Chemistry/Chapter%205.pdf
4. By the decarboxylation of Furoic acid in quinolone in presence
of copper powder.
5. Synthesis from Mucic Acid:
Furan may be prepared from mucic acid which gives furoic acid on dry
distillation, the latter acid is then decarboxylated at its b.p to Furan.
The hydrolysis(or alcoholysis)of furans involves nucleophilic addition of
water(or an alcohol) to an initially formed cation, giving rise to open
chain 1,4-dicarbonyl compounds or derivatives.
Reaction with Electrophiles-Acylation
Alkylation: It is very low yielding reaction due to
formation of polyalkylated products or polymers
Nitration Mechanism: The reaction in presence of a
nucleophile gives in many cases adducts in which intermediate
instead of undergoing proton loss reacts with nucleophile
Mechanism of Aromatic- furan- Nitration
using AcONO2
Sulphonation: Furan upon sulphonation with pyridine-
sulphur trioxide forms Furan 2 sulphonic acid.
Halogenation of Furan
Halogenation: Furan readily reacts with halogens leading to
the destruction of furan ring and forming halogen acids.
Halogen derivatives of furan may be obtained indirectly. For
example, fuoric acid on bromination gives 5-bromo furoic acid
which upon decarboxylation yields 2-bromofuran.

-CO2
Fomation of 2-chloromercurifuran : Treatment with a
mixture of mercuric chloride and sodium acetate gives 2-
chloromercurifuran which is useful synthetic intermediate as
the mercuric group is replaceable.

HgCl2 Iodine
Sod acetate
Reaction with oxidizing agent
Oxidation of Furan
Mechanism of Aromatic- furan- reaction with
Br2 in methanol
Gattermann-Koch Reaction mechanism
Step 1:The first step of the Gattermann Koch reaction mechanism is the generation of the reactive
species which can later be used to react on the aromatic ring. Since carbon monoxide acts as a lewis
base, it can accept a proton from the hydrochloric acid. This results in a positively charged molecule
which has different resonance structures. One such resonance structure displays a positive charge
on the carbon, explaining the reactivity of the hybrid. This species can act as an electrophile while
reacting with the aromatic ring. However, it is more likely to be the target of a nucleophilic attack
from the chloride ion in the hydrochloric acid.
Step 2:When a Lewis acid (aluminium chloride) is added, it
easily removes a chloride ion from the species. The species
now reverts back to the reactive formyl cation.
Vilsmeier Reaction
The Vilsmeier–Haack reaction (also called the Vilsmeier reaction) is the
chemical reaction of a substituted amide with phosphorus oxychloride
and an electron-rich arene (An arene or aromatic hydrocarbon is a
hydrocarbon with alternating double and single bonds between carbon
atoms forming rings) to produce an aryl aldehyde or ketone. The
reaction is named after Anton Vilsmeier and Albrecht Haack.
Cl will act as a nucleophile and positive
charge on nitrogen is removed.
The lone pair on nitrogen helps pushing the leaving
group out. Here the leaving group is not chlorine.
Pi bond of furan will attack on carbon and the
positive charge on nitrogen is removed.
Cl deprotonates the proton from furan and
the aromaticity is regained
1.Base deprotonates water molecule and OH will attack and
positive charge will be removed.
2.The electron on Nitogen will attack proton attached with
base.
Base deprotonates H and the electrons help
pushing out the leaving group (Me2NH)
Houben Hoesch Acylation
• The Hoesch reaction or Houben–Hoesch reaction is an organic
reaction in which a nitrile reacts with an arene compound to form an
aryl ketone. The reaction is a type of Friedel-Crafts acylation with
hydrogen chloride and a Lewis acid catalyst.
• The mechanism of the reaction involves two steps. The first step is a
nucleophilic addition to the nitrile with the aid of a polarizing Lewis
acid, forming an imine, which is later hydrolyzed during the aqueous
workup to yield the final aryl ketone.
Mechanism
Mannich Reaction
• The reaction is named after chemist Carl MannichThe Mannich
reaction is an electrophilic substitution reaction. The use of strong
acids must be avoided. The reaction can be broken down into two
stages: formation of an iminium ion and electrophilic substitution.
• It is also possible to use activated phenyl groups and electron-rich
heterocycles such as furan, pyrrole, and thiophene.
Mechanism of Mannich reaction
The initial step has to be protonation of the formaldehyde so it can
react with the amine. The formation of the iminium ion can be
reversed if water is added to the final product.
Furans /Pyrrole reacts with the iminium cation mainly at the 2- (or 5-)
position but if these positions are blocked then the reaction will take
place at the 3- and 4- positions.