Micellar Catalysis of Organic Reactions. 18. Basic Hydrolysis of Diazepam and Some N-Alkyl Derivatives of Nitrazepam

Article abstract of DOI:10.1021/jo00365a021

Kinetic and mechanistic studies of the basic hydrolysis of several benzodiazepinone drugs have been carried out in the presence of micelles of cetyltrimethylammonium bromide (CTAB) and in aqueous solution.For diazepam, a change of mechanism from initial azomethine hydrolysis in water to initial amide hydrolysis in the presence of micelles of CTAB is indicated.For nimetazepam and N-benzylnitrazepam, initial amide hydrolysis was observed both in the presence of CTAB and in water.For the latter compounds, strong catalysis (50-100) of amide hydrolysis (phase 1) by micelles of CTAB was observed, while azomethine hydrolysis (phase 2) was only very weakly catalyzed (3-4-fold).For diazepam, the catalysis was smaller (9-18-fold), but this was accompanied by a mechanistic change so that here the actual catalysis of amide hydrolysis is masked.