UNIT 4: HETEROCYCLIC COMPOUNDS- I

CONTENTS

4.1 Objectives
4.2 Introduction
4.3 Classification of heterocyclic compounds
4.4 Nomenclature of heterocyclic compounds
4.5 Molecular orbital picture
4.6 Structure and aromaticity of pyrrole, furan, thiophene and pyridine
4.7 Methods of synthesis properties and chemical reactions of Pyrrole, Furan, Thiophene and
Pyridine
4.8 Comparison of basicity of Pyridine, Piperidine and Pyrrole
4.9 Summary
4.10 Terminal Question

4.1 OBJECTIVES

In this unit learner will be able to

· Know about the most important simple heterocyclic ring systems containing heteroatom
and their systems of nomenclature and numbering.
· Understand and discuss the reactivity and stability of hetero aromatic compounds.
· Study the important synthetic routes and reactivity for five and six member hetero
aromatic compounds.
· Understand the important physical and chemical properties of five and six member hetero
aromatic compounds.
· Know about the applications of these hetero aromatic compounds in the synthesis of
important industrial and pharmaceutical compounds
4.2 INTRODUCTION
Heterocyclic compound is the class of cyclic organic compounds those having at least one hetero
atom (i.e. atom other than carbon) in the cyclic ring system. The most common heteroatoms are
nitrogen (N), oxygen (O) and sulphur (S). Heterocyclic compounds are frequently abundant in
plants and animal products; and they are one of the important constituent of almost one half of
the natural organic compounds known. Alkaloids, natural dyes, drugs, proteins, enzymes etc. are
the some important class of natural heterocyclic compounds. Heterocyclic compounds can be
easily classified based on their electronic structure. Heterocyclic compounds are primarily
classified as saturated and unsaturated. The saturated heterocyclic compounds behave like the
acyclic derivatives with modified steric properties. Piperidine and tetrehydrofuran are the
conventional amines and ethers of this category. However, unsaturated heterocyclic compounds
of 5- and 6- member rings have been studied extensively because of their unstrained nature. The
unstrained unsaturated heterocyclic compounds include Pyridine, Thiophene, Pyrrole, Furan and
their benzo fused derivatives. Quinoline, Isoquinoline, Indole, Benzothiophene, and Benzofuran
are some important example of benzo fused heterocycles. Heterocyclic compounds have a wide
application in pharmaceuticals, agrochemicals and veterinary products. Many heterocyclic
compounds are very useful and essential for human life. Various compounds such as hormones,
alkaloids antibiotic, essential amino acids, hemoglobin, vitamins, dyestuffs and pigments have
heterocyclic structure.
In the present unit, students would be able to learn about the common five and six membered
heterocyclic compounds, such as Pyrrole, Furan, Thiophene, Pyridine and Piperidine etc.

4.3 CLASSIFICATION OF HETEROCYCLIC COMPOUNDS

Based on the structural and electronic arrangement the heterocyclic compounds may be classified
into two categories.
i. Aliphatic heterocyclic compounds
ii. Aromatic heterocyclic compounds
The aliphatic heterocyclic compounds are the cyclic amines, cyclic amides, cyclic ethers and
cyclic thioethers. Aliphatic heterocycles those do not contain double bonds are called saturated
heterocycles. The properties of aliphatic heterocycles are mainly affected by the ring strain.
Examples of aliphatic heterocyclic compounds are shown in figure 1.

HN O S O NH S
Aziridine Ethylene oxide Thiirane Oxetane Azetidine Thietane

O NH
O
O O NH
O
Tetrahydrofuran 1,2-dioxane 1,4-dioxane Pyrrolidine Piperidine
(THF)
Figure 1. Examples of aliphatic heterocyclic compounds

However, aromatic heterocyclic compounds are analogous of benzene. The aromatic heterocyclic
compounds also follow the Huckel’s rule. According to Huckel’s rule an aromatic compounds
must be cyclic in nature with planar geometry due to conjugate double bonds and must have
(4n+2)! electrons. Examples of aromatic heterocyclic compounds are shown in figure 2.
O NH S O
N

N
H
Furan Pyrrole Thiophene Pyridine Indole Benzofuran

H
N N HN O NH
N
N N
N
Carbazole Quinoline Isoquinoline Imidazole Oxazole Pyrazole
N N N
N N
N
N N
H
Pyridazine Pyrimidine Purine

Figure 2. Examples of aromatic heterocyclic compounds

A hetero cyclic ring may comprise of three or more than three atoms, which may be saturated or
unsaturated. Also heterocyclic ring may contain more than one heteroatom which may be either
similar or different.
Based on the variety of structure, the heterocyclic compounds may also be divided in to three
categories.
1. Five membered heterocyclic compounds: These heterocyclic compounds may be
considered to be derived from benzene by replacing one C=C bond by a hetero atom with
a lone pair of electron. Based on number of hetero atom present in the cyclic ring this
class of heterocyclic compounds may be further subdivided in to following categories.
a). Heterocyclic compounds with one hetero atom: Common examples of this class of
compounds are furan, thiophene and pyrrole (Figure 3).
O NH S

Furan Pyrrole Thiophene

Figure 3. Five member heterocyclic compounds with one hetero atom

b). Heterocyclic compounds with more than one hetero atom: These hetero atoms may be same
or different. Common examples of this category of heterocyclic compounds are pyrazole,
imidazole, thiazole, oxazole, triazole and tetrazole etc (Figure 4).
NH HN O S HN N HN N

N N N N
N N N
Pyrazole Imidazole Oxazole Thiazole Traizole Tetrazole

Figure 4. Five member heterocyclic compounds with two hetero atom

2. consi
Six membered heterocyclic compounds: This class of compounds may be considered to
be derived from the replacement of a carbon atom of benzene by an iso-electronic atom.
Similar to the five membered heterocyclic compounds, the six membered heterocyclic
compounds may also be subdivided in to following categories.
a). Heterocyclic compounds with one hetero atom: Common examples of this class of
compounds are pyridine, pyran, thiopyran etc (Figure 5).

N O S

pyridine 4H-pyran 4H-thiopyran

 Figure 5. Six member heterocyclic compounds with one hetero atom

b). Heterocyclic compounds with more than one hetero atom: Common examples of this class of
compounds are pyridazine, pyrimidine, pyrazine etc (Figure 6).
N
N N N
N
N
pyridazine pyrimidine pyrazine

Figure 6. Six member heterocyclic compounds with more than one hetero atom

3. Fused or condensed heterocyclic compounds: This class of compound may consist two
or more fused rings which may be partly carbocyclic and partly heterocyclic, common
examples of this category of heterocyclic compounds are Indole, Quinoine,
Isoquionoline, Cabazole etc; or may be completely heterocyclic, common examples of
this category of heterocyclic compounds are purine, pteridine etc (Figure 7).
H
N N
O

N
H
Indole Benzofuran Carbazole Quinoline

N N N
N N
N N
N N
H
Isoquinoline Purine Pteridine
Figure 7. Fused or condensed heterocyclic compounds

4.4 NOMENCLATURE OF HETEROCYCLIC COMPOUNDS

The nomenclature of heterocyclic compounds is divided in to two categories, a) Trivial method
of nomenclature and, b) Systematic method of nomenclature. However, most of the heterocyclic
compounds are known by their common trivial names.

4.4.1 TRIVIAL METHOD OF NOMENCLATUTRE:

During the early days of organic chemistry, names of the heterocyclic organic compounds were
given based on their occurrence, their first preparation and some characteristic properties.
Heterocyclic compounds were named on the basis of their source from which the compound was
obtained. Thus the name depended on the source of the compound. For example picoline;
picoline is derived from coaltar. This is based on Lattin word pictus means tarry.

N CH3
Picoline
Heterocyclic compounds were also named on the basis of their characteristic properties. For
example, pyrrole; which is basic in nature; the name of pyrrole was originated from the Greek
word for fiery red because of characteristic colour which the compound gives with pine splint
dipped in hydrochloric acid.

N
H
Pyrrole
Similarly, the name Furfural is given based on it’s source. Furfural means barn oil. Furfural was
isolated from the distillation of barn.

O CHO
Furfural
The trivial nomenclature was the first nomenclature method which has a significant role in the
development of heterocyclic chemistry. However, this system has some disadvantages too. The
trivial system does not give any structural information about the compound. At present just over
60 trivial names survive and recognized by IUPAC system of nomenclature. These recognized
names are, however, significant because they are used as basis for constructing other compounds,
more systematic names for polycyclic compounds and/or their derivatives. Examples of
heterocyclic compounds with recognized trivial names are shown in figure 8.
 NH O S NH HN
N N
Pyrrole Furan Thiophene Pyrazole Imidazole
N
O O N N N

N
N N
Oxazole Isooxazole Pyridine Pyridazine Pyrimidine

H
N O N

N N
Pyrazine Pyran Pyrrolizine Indole
H
N N
NH N
N

Isoindole Indazole Indolizine Quinoline

N N N
N
N N
N
Isoquinoline Quinazoline Pteridine

Figure 8. Some heterocyclic compounds with recognized trivial names

4.4.2 SYSTENATIC METHOD OF NOMENCLATUTRE:

This is most widely used nomenclature system for monocyclic heterocyclic compounds
especially for three to ten membered ring systems. These members have various degree of
unsaturation containing one or more heteroatoms. The systematic nomenclature gives important
structural information. The most relevant system that is recommended by IUPAC for
nomenclature of heterocyclic compounds is the Hantzch-Widmann system of nomenclature.
This nomenclature system specifies the nature, position, ring size, number, and types of
heteroatoms present in any heterocyclic compounds. This systematic method generally derived
the nomenclature using the following syntax;
 Name: Prefix + Stem + Suffix

Following are the important points to be remembered during the systematic nomenclature of
heterocyclic compounds.
1. In this nomenclature the nomenclature of heterocyclic compounds are assigned by
combining ‘prefix’ (that indicate the heteroatom present) with ‘stem’ (that indicate the
ring size as well as the saturation and unsaturation in the ring) and ‘suffixes’. The
common prefixes are shown in Table 1. It should be noted that final ‘a’ is dropped when
prefix is followed by vowel.
2. Nomenclature of heterocyclic compound starts with the heteroatom appears first in the
table 1.
3. If more than two different heteroatoms are present in any heterocyclic compound the
prefixes are listed in order in which they are appear in above table (Table 1).
4. If there are two or more than two hetero atoms of same types are present in a
heterocyclic compound they are indicated by di-, tri- etc.
5. The position of saturated atom is numerically indicated with prefix ‘H-’ as a part of the
name of the ring system. It should be noted that where, there is a choice of numbering,
the indicated position is given the lowest possible number.
6. The size of a monocyclic ring (three to ten membered rings) is indicated by stem. The
common ‘stem’ nomenclature is given in Table 2.
Table 1: Common Prefix for Heteroatoms (arranged in the preferential order)

S. No. Heteroatom Symbol Prefix

1 Oxygen O Oxa
2 Sulphur S Thia
3 Selenium Se Selena
4 Nitrogen N Aza
5 Phosphorous P Phospha
6 Arsenic As Arsa
7 Antimony Sb Stiba
8 Bismuth Bi Bisma
9 Silicon Si Silia
 10 Tin Sn Stanna
11 Lead Pb Plumba
12 Boron B Bora
13 Mercury Hg Mercura

Table 2: Common Prefix for Heteroatoms (arranged in the preferential order)

S.No Ring Size Unsaturated Ring Saturated Ring

1 3 iren Irane
2 4 ete Etane
3 5 ole Olane
4 6 ine Inane
5 7 epine Epane
6 8 ocine Ocane
7 9 onine Onane
8 10 ecine Ecane

Some examples of heterocyclic compounds with systematic nomenclature are shown in figure 9.
H
N N O S S

2H-azirine aziridine oxirane thiirane thiirene

HN N O S

azetidine 2,3-dihydroazete oxetane thietane

N
N O NH O
O
N
N N
1,3-diazete 1,2-oxazetidine 1,3-dioxolane 1,2,4-triazine

S N
thiepane (azocine
Figure 9. Examples of some heterocyclic compounds with systematic names