Journal of the Chinese Chemical Society p. 277 - 284 (1998)
Update date:2022-08-24
Topics:
Yang, Shen K.
Diazepam (1) is a frequently prescribed hypnotic/anxiolytic drug in worldwide use. Compound 1 is hydrolyzed in alkaline medium to form 2-methylamino-5-chlorobenzophenone imine (2) and 2-methylamino-5-chlorobenzophenone (3); the ratio of 2:3 increases with increasing NaOH concentration (J. Pharm. Sci. 85, 745-748, 1996). The mechanism in the conversion of 1 to 2 and 3 via various intermediates is the subject of this report. Results of hydrolysis kinetics and structural identification of some intermediate products indicated an initial hydroxide attack at the C2-carbonyl carbon of 1, resulting in the formation of a dioxide (7, 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2,2-dioxide). Compound 7 was characterized by proton NMR spectroscopy and via its monomethyl ether (8, 7-chloro-1,3-dihydro-2-hydroxy-2-methoxy-1-methyl-5-phenyl-2H-1,4-benzodiazepme) . The seven-member diazepine ring of 7 opened at the N1-C2 bond to form aglycinate [5, 2-methylamino-5-chloro-α-(phenylbenzylidene)glycinate]. Compound 7 (and/or 5) underwent an additional hydroxide attack at the C5-N4 imine bond to form a tetrahedral intermediate, which decomposed to form 2 and 3.
View MoreHunan Zhongqi Pharmaceutical Co., Ltd
website:http://www.hnzqzy.com
Contact:0730-8722288 13807308622
Address:Wanjiafan Road ,Yueyang Economic And Technological Development Zone ,Hunan,PRC
Contact:+86-25-83719363
Address:106-7 Chunnan Rd, Chunxi Town, Gaochun, Nanjing, China
ShenZhen InnoSyn Biotech Co.,Ltd
website:http://www.innosyns.com
Contact:+86-755-28351685
Address:Floor 5 & 6, Building A1, HAIKEXING Strategic Innovative Industrial Park, 16 BaoShan Road, PingShan District
website:http://www.oceanchem-group.com
Contact:86-536-8596048
Address:9th floor,Building B future Plaza, No.88.Fenghuang Street,Weifang,Shandong,China
Qingdao S. H. Huanyu Imp. & Exp. Co., Ltd.
Contact:86-532-88250866
Address:Room 615, World Trade Centre Building B, Hongkong Middle Roda 6#, Qingdao, Shandong, China
Doi:10.1016/j.jorganchem.2013.02.005
(2013)Doi:10.1007/s10593-005-0077-8
(2004)Doi:10.1021/jm010511b
(2002)Doi:10.1002/anie.201903890
(2019)Doi:10.1039/c7ob00062f
(2017)Doi:10.1016/j.jfluchem.2006.12.006
(2007)