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Reactions of 7‐Chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2 H ‐1,4‐benzodiazepin‐2,2‐dioxide in Various pH Solutions
Author(s) -
Yang Shen K.
Publication year - 1998
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.199800096
Subject(s) - chemistry , hydrolysis , oxygen , aqueous solution , kinetics , oxygen atom , medicinal chemistry , inorganic chemistry , organic chemistry , molecule , physics , quantum mechanics
Diazepam ( 1 ) is a frequently prescribed hypnotic/anxiolytic drug worldwide. 7‐Chloro‐1,3‐dihydro‐l‐methyl‐5‐phenyl‐2 H ‐1,4‐benzodiazepin‐2,2‐dioxide ( 2 ) is an initial alkaline hydrolysis product of 1. The mechanisms in the conversion of 2 to 2‐methylamino‐5‐chloro‐α‐(phenylbenzylidene)glycinate ( 3 ), 2‐methylamino‐5‐chlorobenzophenone ( 4 ), and 1 in aqueous solutions with pH ranging from 0 to 12.2 is the subject of this report. Results of temperature‐dependent hydrolysis kinetics and product identification indicated 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 with decreasing pH and became less sentitive to pH at pH ≤ 4.5. (3) In solutions with pH between 0 and 2, 2 was rapidly converted 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 following conversion to 1 in 1 M HCl. In addition to understanding the mechanism in the transformations of 2 in various pH solutions, this study established 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 position.