Benzopyridines Quinoline and Isoquinoline:: Heterocyclic Chemistry
Benzopyridines Quinoline and Isoquinoline:: Heterocyclic Chemistry
Benzopyridines Quinoline and Isoquinoline:: Heterocyclic Chemistry
N
S Benzopyridines
O Quinoline and
Isoquinoline:
1
Heterocyclic Chemistry
Introduction :
N
N
Quinoline Isoquinoline
Benzo[b]pyridine Benzo[c]pyridine
2
Heterocyclic Chemistry
Occurrence of quinolone and isoquinoline
Quinoline alkaloids
3
Emetine is a drug used asan anti-protozoal Heterocyclic Chemistry
Basicity
4
Heterocyclic Chemistry
Preparation of Quinoline
1. Friedländer Synthesis
O
CH O H2O, NaOH, 50 ºC
+
H
N
NH2
Enolizable 85%
2-Aminobenzene- carbonyl
carboxaldehyde compound
Paul Friedländer
(1857 - 1923) 5
Heterocyclic Chemistry
Preparation of Quinoline
2- Skraup’s Synthesis
General Equation:
CH2
CH 2OH O
NH2 CH 2
CH
CHOH
-H2O CH 2
C
CH 2OH N
H O H
Glycerol Acroline
-H2O
C6H5NO2
Oxidation
N N 6
Heterocyclic Chemistry H
Preparation of Isoquinoline
Bischler-Napieralski Synthesis
NH N
R -H2O
O
+ Pd, 200 ºC, R
H - H2
R
Electrophilic aromatic substitution in quinoline and
Isoquinoline
9
Heterocyclic Chemistry
Electrophilic aromatic substitution in quinoline and
Isoquinoline
10
Heterocyclic Chemistry
Nucleophilic aromatic substitution in quinolines and
Isoquinolines
Quinoline and isoquinoline undergo facile nucleophilic
substitution as in pyridine.
Quinoline undergoes Chichibabin reaction to give 2-amino-
quinoline 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.
11
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
12
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
13
Heterocyclic Chemistry
Oxidations
Quinoline and isoquinoline undergo oxidative cleavage with
alkalian potassium permangnate to give pyridine-2,3-
dicarboxylic 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.
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Heterocyclic Chemistry