Page 64 - Pharmaceutical Organic Chemmistry-3 (Theoritical book) 24-25

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

Closely related to Skraup synthesis and consists of heating aniline with aldehydes in
the presence of HCl, e.g. acetaldehyde forms in situ crotonaldehyde which then

undergoes a 1,4-addition with aniline.

2 CH3CHO CH3CH=CHCHO

crotonaldhyde

O OH
H H 1,4- H cyclization
N: addition N - H O
2
H CH 3 CH 3
H

PhN=CHCH 3

N CH 3 - 2H N CH 3
H

2-methylquinoline
(quinaldine)
2) From ortho-acylanilines and carbonyl compounds:

H
O
R H R
NH 2 O - 2H O N
2

o-Acylanilines react with ketones (or aldehydes) having an -methylene to give

quinolines.

1- Pfitzinger reaction:

This is carried out by heating isatin with alkali in the presence of a ketone. Hydrolysis

of isatin gives o-aminophenylglyoxylate which reacts with the ketone giving the easily

decarboxylated quinoline-4- carboxylic acid.

O COONa

3
N O NaOH C O + CH COCH 3
H NH 2
isatin o-aminophenylglyoxylate