REACTIONS OF 1-METHYL-5-PHENYL-2H-1,4-BENZODIAZEPIN-2,2-DIOXIDE IN VARIOUS PH SOLUTIONS

Diazepam (1) is a frequently prescribed hypnotic/anxiolytic drug world wide. 1-methyl-5-phenyl-2H-1,4-benzodiazepin-2,2-dioxide (2) is an ini tial alkaline hydrolysis product of 1. The mechanisms in the conversio n of 2 to lamino-5-chloro-alpha-(phenylbenzylidene)glycinate (3), 2-me thylamino-5-chiorobenzophenone (4), and 1 in aqueous solutions with pH ranging from 0 to 12.2 is the subject of this report. Results of temp erature-dependent hydrolysis kinetics and product identification indic ated that: (1) in solutions with pH between 7 and 12.2, 2 underwent a ring-opening reaction to form 3; the rate decreased with increasing pH . (2) In solutions with pH between 2 and 7, 2 was rapidly converted to 3, followed by a pH-dependent conversion to 4; the rate increased wit h decreasing pH and became less sentitive to pH at pH less than or equ al to 4.5. (3) In solutions with pH between 0 and 2, 2 was rapidly con verted to 4 and 1; the percentage of 1 increased with decreasing pH. ( 4) A 2 containing one oxygen-18 atom lost 50% of its oxygen-18 followi ng conversion to 1 in 1 M HCl. In addition to understanding the mechan ism in the transformations of 2 in various pH solutions, this study es tablished a simple and efficient method in the quantitative conversion of 1 to 4 and in the preparation of an oxygen-18-containing 1 at C2 p osition.