BASE-CATALYZED KETO-ENOL-TAUTOMERISM OF DIAZEPAM

The hydrogens at 3-position of diazepam, a frequently prescribed anxio lytic drug worldwide, undergo an efficient exchange with deuterium ato ms in alkaline deuterated methanol. The position of deuterium exchange is confirmed by proton nuclear magnetic resonance and mass spectral a nalyses. A base-catalyzed keto-enol tautomerism is proposed to be resp onsible for the observed deuterium exchange. This finding has been app lied to the preparation of tritium-labeled diazepam in which only arom atic protons are labeled with tritium atoms. A tritium-labeled diazepa m lacking tritium atoms at 1 and 3 positions is valuable as a substrat e for quantitative metabolism studies.