Heterocyclic Chemistry

N
S
O

Benzopyridines
Quinoline and
Isoquinoline:

Heterocyclic Chemistry

Introduction:

N
N

Quinoline
Benzo[b]pyridine

Isoquinoline
Benzo[c]pyridine

Quinolizinium ion
Benzo[a]pyridinium
Heterocyclic Chemistry

Introduction :
Quninoline
and isoquinoline are two fused
heterocycles derived by fusion of pyridine ring
with a benzene ring.
Quinoline is high boiling liquid (b.p. 237C) and
smells like pyridine while isoquinoline is a low
melting solid (m.p. 26.5C, b.p. 243C).
Both quinoline and isoquinoline are planar 10electron aromatic systems in which all atoms are
sp2 hybridized and contribute one electron each in
orthogonal p-orbitals for delocalization over the
rings with resonance energies of 198 and 143
KJ/mol respectively
Heterocyclic Chemistry

Resonance structures of Quinoline and isoquinoline

Occurrence of quinoline
Both
ring systems occur naturally and were
originally isolated from coal tar.

Heterocyclic Chemistry

Occurrence isoquinoline

Emetine is a drug used as both an

anti-protozoal and to induce vomiting

It is a toxic crystalline alkaloid

It inhibits protein synthesis and
may inhibit ascorbic acid
biosynthesis
it serves some interest in the study of
certain yeasts
Heterocyclic Chemistry

Basicity

Quinoline and isoquinoline are weak bases but

slightly more basic than pyridine (why?) but less
basic than anilines since the nitrogen in quinoline
and isoquinoline is more electronegative being sp 2
hybridized compared to sp3 hybridized nitrogen of
anilines.

Heterocyclic Chemistry

Preparation of Quinoline

1. Friedlnder Synthesis
O
O

CH

H2O, NaOH, 50 C
H

NH2

2-Aminobenzenecarboxaldehyde

Enolizable
carbonyl
compound

85%

Paul Friedlnder
(1857 - 1923)

Preparation of Quinoline

2- Skraups Synthesis
General Equation:
H
CH2

CH 2OH
CHOH
CH 2OH

Glycerol

-H2O

CH 2

C
H

CH 2

NH2

CH

N
H

Acroline

-H2O

C6H5NO2
Oxidation
N

N
H

Preparation of Isoquinoline

Bischler-Napieralski Synthesis
POCl3, P2O5, 100 C
NH

R
O

-H2O

Pd, 200 C,
- H2

Electrophilic
Isoquinoline

aromatic

substitution

in

quinoline

and

The nitrogen of the quinoline and isoquinoline has deactivating

effect on the ring towards electrophilic substitution as in case
of pyridine. However electrophilic substitution of quinoline and
isoquinoline requires less vigorous conditions than pyridine.
Consequently electrophilic aromatic substitution occurs at the
benzene ring at positions 5 and 8.
Heterocyclic Chemistry

Electrophilic aromatic substitution in quinoline

and isoquinoline

Electrophilic
Isoquinoline

aromatic

substitution

in

quinoline

However, nitration can take place at pyridine ring using

nitric acid and acetic anhydride at position 3 in case of
quinoline and at position 4 in case of isoquinoline

and

Nucleophilic aromatic substitution in quinolines and

Isoquinolines
Quinoline and isoquinoline undergo facile nucleophilic
substitution as in pyridine.
Quinoline undergoes Chichibabin reaction to give 2-aminoquinoline while isoquinoline undergoes Chichibabin reaction to
give 1-amino isoquinoline . Isoquinoline undergoes substitution
faster than quinoline. The reaction proceeds in a manner
analogues to pyridine.

Heterocyclic Chemistry

Reduction of quinoline
The pyridine ring is more easily reduced
Quinoline can be selectively reduced at 1,2-bond by reaction
with lithium aluminium hydride but the 1,2-dihydro quinolines
are unstable and disproportionate easily to give quinoline and
1,2,3,4-tetrahydroquinoline.
Quinoline can be converted to 1,2,3,4-tetrahydroquinoline
by catalytic hydrogenation or with tin and hydrochloric acid

Heterocyclic Chemistry

Reduction of isoquinoline
The pyridine ring is more easily reduced
Isoquinoline can also be converted to 1,2-dihydro or
1,2,3,4-tetrahydroisoquinoline
with
diethyl
aluminium hydride and sodium-ethanol, respectively

Oxidations
Quinoline and isoquinoline undergo oxidative cleavage with
alkalian potassium permangnate to give pyridine-2,3dicarboxylic
acid
and
pyridine-3,4-dicarboxylic
acid
respectively.
However, pyridine-2,3-dicarboxylic acid is not stable and
undergoes decarboxylation to give nicotinic acid. Quinoline
and isoquinoline both form N-oxides when treated with
hydrogen peroxide in acetic acid or with organic peracids.

Thanks for your attention

Heterocyclic Chemistry