Micellar catalysis of organic reactions. XIV. Hydrolysis of some 1,4-Benzodiazepin-2-one drugs in acidic solution

Abstract

Kinetic studies of the acidic hydrolysis of diazepam and nitrazepam were carried out in the presence of micelles of sodium dodecyl sulfate (sds). The hydrolysis of diazepam was shown to occur with biphasic kinetics. This is consistent with initial hydrolysis of the azomethine bond followed by very slow hydrolysis of the amide bond as found for hydrolysis in aqueous solution. Nitrazepam, however, was found to decompose with monophasic kinetics consistent with initial amide hydrolysis. Reactions involving the hydrolysis of the azomethine bond were shown to be independent of acid concentration and subject to inhibition by micelles of sds. Reactions involving amide hydrolysis were shown to be first order in acid concentration and subject to micellar catalysis. The mechanistic change for the hydrolysis of nitrazepam on transfer from water (initial azomethine cleavage) to micelles of sds (initial amide cleavage), was presumably the result of the inhibition of azomethine hydrolysis and the catalysis of amide hydrolysis by the micelles.