Base-catalysed rearrangement of temazepam.
Temazepam undergoes a rearrangement reaction in strongly alkaline media to form a cyclic diamide, 7-chloro-1-methyl-5-phenyl-4,5-dihydro-2H-benzodiazepin-2,3(1H)-di one. Thermodynamic parameters (Eact, delta H++, delta S++, delta G++) involved in the rearrangement reaction, studied using either CH3CN-0.2 N NaOH in H2O (1:1, v/v) or CH3CN-0.2 N NaOD in D2O (1:1, v/v) as the solvent, were similar with an isotope effect (kH/kD) of 0.77 +/- 0.03. Kinetics of the rearrangement reaction were studied as a function of NaOH concentration, temperature and ionic strength. Results indicated that the rate-determining step did not involve proton exchange with solvent. Mass spectral analysis of the cyclic diamides derived by using either D2O or H2(18)O in the solvent mixtures suggested that the formation of the cyclic diamide involved a nucleophilic addition of a hydroxide ion at the C2 carbonyl carbon of temazepam.
Yang
S K
SK
Department of Pharmacology, F. Edward Hébert School of Medicine Uniformed Services, University of the Health Sciences, Bethesda, MD 20814-4799.
D002851:Chromatography, High Pressure Liquid; D007554:Isotopes; D007700:Kinetics; D013058:Mass Spectrometry; D013053:Spectrophotometry; D013693:Temazepam / Q000032:analysis / Q000737:chemistry*
D007554:Isotopes; D013693:Temazepam