Kinetics of hydrolysis of oxazolam in aqueous solution

The hydrolysis reaction of oxazolam, a representative of 1, 4-benzodiazepinooxazoles (BDOZ), was investigated kinetically. The reaction product was identified by thin layer chromatography (TLC) and infrared (IR) spectroscopy, and it was concluded that irreversible hydrolytic cleavage took place at the diazepinone nucleus. The rate constant was determined by ultraviolet (UV) spectroscopy. The reaction was a first-order process consisting of two parallel reactions with different reacting species of oxazolam, depending on the pH of the medium. The pH-rate profile obtained for the reaction suggested that the reaction was independent of hydrogen ion concentration in acidic media, while it was catalyzed by hydroxide ion in alkaline media. The nonlinear least-squares fit method was employed to determine the catalytic rate constants involved in the equation describing the pH-rate constant relationship. Activation energies as well as other thermodynamic parameters were obtained in media of pH 2.0 and 8.0, and the values confirmed that different chemical species of oxazolam were involved. The observed effect of buffer concentration indicated that general base catalysis was involved in the reaction of the ionized species of oxazolam. A mechanistic consideration indicated that the rate-determining step may be the nucleophilic attack of a water molecule or hydroxide ion at the 11b-position in the diazepinone nucleus.