HETEROCYCLIC CHEMISTRY

Lecture notes 17/03/2020 (11-12pm).

ISOQUINOLINE
Isoquinoline is a heterocyclic aromatic organic compound. It is a structural isomer of
quinoline. Isoquinoline and quinoline are benzo pyridines, which are composed of a benzene
ring fused to a pyridine ring.

(IUPAC name Isoquinoline; other names: 2-azanaphtalene, Benzo[c]pyridine, 2-benzanine)

GENERAL PROPERTIES
1) Isoquinoline is a crystalline substance with a quinoline like odour.
2) Its melting point is 24.6°C
3) Isoquinoline is a colourless hygroscopic liquid at NORMAL ROOM temperature
4) low soluble in water but dissolve well in ethanol, acetone, diethyl ether, carbon
disulphide, and other common organic solvents.
Aromacity
Rule-1: Cyclic

Yes, isoquinoline cyclic and planner in nature (obeys Huckle rule -1)

Rule-2: Pi electron on each atom

Pi electrons is about 10 (each atom in the cyclic or planner form holds at
list ONE pi electron) (obeys Huckle rule -2).

Rule-3: 4n+2=Pi electrons

4n+2=Pi electrons
(Pi electrons=10) from above rule-2.
4n+2=10 Pi electrons
4n=10-2 Pi electrons
4n=8
n=2 Rings

LECTURE NOTES _PHARMACEUTICAL ORGANIC CHEMISTRY-III

(DR) SHARFUDDIN MOHD (24485)
(BP401T). B. PHARM-IV SEM_LOVELY PROFESSIONAL UNIVERSITY.
 HETEROCYCLIC CHEMISTRY

LECTURE NOTES _PHARMACEUTICAL ORGANIC CHEMISTRY-III

(DR) SHARFUDDIN MOHD (24485)
(BP401T). B. PHARM-IV SEM_LOVELY PROFESSIONAL UNIVERSITY.
 HETEROCYCLIC CHEMISTRY

Quinoline & Isoquinoline both have….

1) Have basic, pyridine like nitrogen atoms, which undergo electrophilic substitutions.
2) less reactive toward electrophilic substitution than benzene because of the nitrogen
atom that withdraws electrons from the ring.
3) Electrophilic substitution occurs on the benzene ring rather than on the nitrogen-
containing pyridine ring and a mixture of substitution products is obtained

In quinoline and isoquinoline the N-atom withdrawn electron in pyridine ring thus few are
available for Electrophilic Aromatic Substitution (EAS), therefore E+ prefers to go to benzene
ring.

LECTURE NOTES _PHARMACEUTICAL ORGANIC CHEMISTRY-III

(DR) SHARFUDDIN MOHD (24485)
(BP401T). B. PHARM-IV SEM_LOVELY PROFESSIONAL UNIVERSITY.
 HETEROCYCLIC CHEMISTRY

Oxidation and

N
in
NaNH 2ibab
sch NH2
hit
tsc ction 1-amino isoquinoline
rea
N eth
er
C2H5MgBr

C2H5
1-ethyl isoquinoline
3 Oxidation Reaction
Isoquinoline is oxidised by alkaline KMno4 to form equimolar mixture of phthalic acid
and cinchomernoic acid.

COOH HOOC
O +
N N
KMno4
COOH HOOC
isoquinoline
phthalic acid cinchomeronic acid
4 Reduction reaction

Sn/HCL
H2/Pt
NH N NH
Octa- hydro isoquinoline 1,2,3,4 tetrahydro isoquinoline
Birch Reduction
Na in NH3

NH
1,2 di hydro isoquinoline

LECTURE NOTES _PHARMACEUTICAL ORGANIC CHEMISTRY-III

(DR) SHARFUDDIN MOHD (24485)
(BP401T). B. PHARM-IV SEM_LOVELY PROFESSIONAL UNIVERSITY.
 HETEROCYCLIC CHEMISTRY

MEDICINAL USES OF ISOQUINOLINE

S CATEGOR EXAMPLE STRUCTURES

N Y
O
1 Antihypertens QUINOPRIL
ive QUNINAPIRITAT

2 Anaesthetic DIMETHISOQUIN
agents

3 Disinfectant N-LAURYLISOQUINOLINE

4 Antifungal 2-2
HEXADECAMETHYLENEDISOQUI
NOLINE
5 Vasodilator PAPAVERINE

LECTURE NOTES _PHARMACEUTICAL ORGANIC CHEMISTRY-III

(DR) SHARFUDDIN MOHD (24485)
(BP401T). B. PHARM-IV SEM_LOVELY PROFESSIONAL UNIVERSITY.