Hydrolysis of 2-oxoquazepam in alkaline solution.
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-alpha-(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 degrees C (delta H++ = 13.8 kcal/mol, delta S++ = -31.2 cal/K/mol, and delta G++ = 23.1 kcal/mol).
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Department of Pharmacology, F. Edward Hebert School of Medicine, Uniformed Services, University of the Health Sciences, Bethesda, MD 20814-4799.
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D014151:Anti-Anxiety Agents / Q000737:chemistry*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D013816:Thermodynamics
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001569:Benzodiazepines; C039103:2-oxoquazepam