Page 66 - Pharmaceutical Organic Chemmistry-3 (Theoritical book) 24-25

Clinical Pharmacy PharmD - 2024/2025 Level 2 Pharmaceutical Organic Chemistry-3 (PC 305)

2) Electrophilic substitution:

Electrophilic substitution reactions of quinoline and isoquinoline, similar to pyridine,

require vigorous conditions. Generally, quinoline is attacked preferentially at position

8, while isoquinoline at position 5, then at position 8. In acid solution, the quinolinium

or isoquinolinium ion is the active reactant (cf. pyridine).

i. Nitration

Quinoline gives a mixture of approximately equal ratio of 5- and 8-nitroquinoline,

whereas isoquinoline produces almost exclusively the 5-nitro isomer.

NO 2
HNO /H SO 4
3
2
+
N N
N
NO 2
5-nitroquinoline 8-nitroquinoline