Conversion of Quazepam to 2-Oxoquazepam in Alkaline Solution

SHEN K. YANG AND MICHAEL S. YANG

Department of Pharmacology, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences Bethesda, Maryland 20814-4799, U.S.A.

ABSTRACT

   Quazepam [7-chloro-1-(N-2,2,2-trifluoroethyl)5-(2'-fluorophenyl)-l,3-dihydro-2H-1,4-benzodiazepin-2-thione,QZ], an anxiolytic drug in clinical use, was converted in an alkaline solution to form 11 detectable poroducts. 2-Oxoquazepam [7-chloro-1-(N-2,2,2-trifluoroethyl)-5-(2'-fluorophenyl)-l,3-dihydro-2H-1,4-benzodiazepin-2-one, OQZ] was the most abundant product formed. Reaction kinetics in alkaline solutions were analyzed by reversed-phase high-performance liquid chromatography, Time-dependent ultraviolet-visible absorption spectral measurements indicated an initial formation of an intermediate, followed by the formation of OQZ as the most abundant product. The electron-deficient C2 carbon of QZ probably undergoes a nucleophilic addition reaction by a hydroxide ion, resulting in the formation of primarily OQZ and other minor products.

Key words : Quazepam, 2-oxoquazepam, Kinetics, Spectrophotometry