Page 64 - Org 3 theoritical book 2024-25

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

COONa
C COONa
O CH - OH 1) H +
N C 3 CH 2)  / -CO 2 N CH 3
CH 3 N 3
2-methylquinoline- quinaldine
4-carboxylic acid

II- Isoquinolines

1) From arylethylamines:

The reaction of -arylethylamines with acid derivatives or with aldehydes gives

amides or imines that can be cyclized to 3,4-dihydro- or 1,2,3,4-

tetrahydroisoquinolines, respectively. Subsequent dehydrogenation produces the fully

aromatic isoquinolines.

A- Bischler-Napieralski reaction:

This important route is used for the preparation of isoquinolines substituted at 1-

position. It involves the cyclodehydration of N-acyl--phenylethylamines by heating

with POCl 3, P 4O 10, PPA or anhydrous ZnCl 2. The formed 3,4-dihydroisoquinolines are

then oxidized or dehydrogenated to the isoquinoline derivatives:

acylation POCl 3
+
NH 2 O NH NH
C R C
-phenylethylamine R OPOCl 2
N-acyl--phenylethylamine

Pd-C
-H + C N H Cl - HOPOCl 2 N -2H N
R O P O R R
Cl 1-substituted-3,4- 1-substituted
dihydroisoquinoline isoquinoline

Properties and reactions of quinoline and isoquinoline:

1) Quinoline and isoquinoline, like pyridine, are tertiary basic compounds;

isoquinoline (pK a 5.4) is stronger base than pyridine (pK a 5.2) which, in turn, is

stronger than quinoline (pK a 4.9). Both can form salts with most inorganic acids by

protonation on nitrogen and forms N-oxides and quaternary salts as given by pyridine.