Cis/trans isomerization and proton exchange reactions of 3,11b-dimethylbenzodiazepinooxazole

Abstract

The cis/trans isomerization and proton exchange reactions of 3,11b-dimethylbenzodiazepinooxazole (1) in methanol-d 4 were investigated kinetically by 1H-NMR spectroscopy. The 3-methyl protons of 1 were followed during the process of isomerization and the pseudo first-order rate constant was determined to be 1.41 × 10 2 min −1 ( t 1 2 = 49.1 min ) at 23°C, irrespective of whether starting material consisted of cis or trans crystals. At equilibrium the cis/trans ratio of 1 was found to be 6.9:1. The lib-methyl protons of 1 were observed to participate in proton exchange with deuterium in methanol-d 4. The lib-methyl signals of the trans isomer of 1 decreased in strength on the basis of the parallel reactions of proton exchange and cis/trans isomerization. The time courses of the individual signals were simulated by means of an analogue computer. The proton exchange rate constant of 1 amounted to a value of 2.56 × 10 −2 min −1 ( t 1 2 = 27.1 min ) at 23°C. A reaction mechanism involving an iminium-type intermediate was proposed to account for the isomerization and proton exchange reactions. The proton exchange rate constant for 1 was compared with those for 2-substituted derivatives reported previously.