Acid hydrolysis of diazepam. Kinetic study of the reactions of 2-(N-methylamino)-5-chlorobenzophenone, with HCl in MeOH-H2O

Abstract

In the acid hydrolysis of diazepam (1), several unusual products, apart from 2-(N-methylamino)-5-chlorobenzophenone (2) and glycine, were isolated. On the assumption that some of those products could arise from further degradation of 2, the reaction of this compound with 0.5-2 M HCl was studied, in 1:1 MeOH-H2O, at 60 and 80 degrees C. Several unexpected products were isolated from the reaction of 2 with HCl, namely, 2-amino-5-chlorobenzophenone (3), 2-(N,N-dimethylamino)-5-chlorobenzophenone (4), 2-(N-methylamino)-3,5-dichlorobenzophenone (5), 2-amino-3,5-dichlorobenzophenone (6), 2,4-dichloro-10-methyl-9,10- acridinone (7), and 2,4-dichloro-9,10-acridinone (8). The methyl transfers, the chlorination, and the cyclization reactions that give rise to products 3-8 are unexpected under the present reaction conditions. The rate of reaction of 2, as well as the rate of formation of compounds 3-6, was measured at several HCl concentrations.