The non-aqueous reactions of some 1,4-benzodiazepines.

The data presented for the behavior of 3-hydroxy-1,4-benzodiazepines during non-aqueous titrations indicate that: (a) the First stage protonation during titration as a base with perchloric acid occurs at the N—4 position and is relatively unaffected by substitution at the 3-position, except when the substituent is electron-withdrawing; (b) deprotonation during titration as an acid with tetrabutylammonium hydroxide occurs at the N-1 position rather than at the 3-OH substituent; (c) the similarity of the u.v. spectra of neutral and basic solutions of lorazepam indicate that a tautomerism in basic solution postulated previously does not occur to any great extent; and (d) titration with tetrabutylammonium hydroxide should be acceptable as an assay method tor lorazepam.