An investigation of the anion chemistry of Diazepam

Abstract

This work describes a convenient procedure for direct functionalization of the 3-position of 7-chloro-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (Diazepam) and should be applicable to other similar benzodiazepinones. The method involves abstraction of a proton from the 3-position of Diazepam by means of lithium cliisopropylamide (LOA) in tetrahydrofuran followed by reaction of the resulting anion with various electrophilic reagents. Some of the electrophilic reagents tried were a series of alkyl halides. These gave good yields of the 3-alkyl substituted benzodiazepinone. Also tried were reactions of the anion of Diazepam with some ketones and benzaldehyde. The yields of tertiary alcohols were low in most cases. Two exceptions were the cyclohexanone and benzaldehyde reactions. For short reaction times, the yields of the corresponding alcohols products were good, but for long reaction times (18 h) the products isolated in good yields were the cyclohexylidine and benzylidine, respectively.