Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines II: oxazepam and diazepam.

The hydrolysis kinetics of oxazepam and diazepam leading to a benzophenone product and a glycine derivative were quantified from pH 1 to 11. For oxazepam, two intermediates were isolated and identified, indicating a parallel consecutive reaction mechanism. The hydrolysis occurred uncatalyzed and demonstrated acid-base catalysis for both reaction steps. One intermediate was observed by TLC for diazepam hydrolysis. This intermediate, resulting from breakage of the azomethine linkage, was different than the major intermediate isolated for oxazepam hydrolytic degradation (amide hydrolysis preferred). Stability parameters involving rate constant-temperature dependence are reported.