Hydrolysis of 2-oxoquazepam in alkaline solution

Article abstract of DOI:10.1002/jps.2600830114

2-Oxoquazepam [7-chloro-1-(N-2,2,2-trifluoroethyl)-5-(2'-fluorophenyl)- 1,3-dihydro-2H-1,4-benzodiazepin-2-one, OQZ], a major pharmacologically active metabolite of quazepam, was hydrolyzed in NaOH solution to form a sodium salt of 2-(N-2,2,2-trifluoroethyl)amino-5-chloro-α-(2'- fluorophenylbenzylidene)glycine. The hydrolysis product was formed via a rapidly established acid-base equilibrium, followed by a rate-determining, ring-opening reaction involving two negatively charged ions. Following neutralization, the hydrolysis product was isolated by reversed-phase HPLC and subsequently identified by its UV-vis absorption and MS analyses. Kinetics of the hydrolysis reaction in acetonitrile/water mixture was studied by reversed-phase HPLC analysis as a function of water content, NaOH concentration, temperature, and ionic strength. In acetonitrile:0.05 N NaOH (1:1, v/v), the hydrolysis of OQZ had an energy of activation of 14.4 kcal/mol and at 25 °C (ΔH((+)) = 13.8 kcal/mol, ΔS((+)) = -31.2 cal/K/mol, and ΔG((+)) = 23.1 kcal/mol).