Medazepam, 2-hydroxy-2-methoxy-

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: Medazepam, 2-hydroxy-2-methoxy-
• 英文别名: 7-chloro-2-methoxy-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-ol
• 化学式: C₁₇H₁₇ClN₂O₂
• 分子量: 316.787
• InChiKey: RTBMWGQHDJEEPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  45.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  硫酸二甲酯 、 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2,2-dioxide disodium salt 在 sodium hydroxide 作用下， 以 氯仿 为溶剂， 反应 2.0h， 生成 (5-氯-2-(二甲氨基)苯基)(苯基)甲酮 、 Medazepam, 2-hydroxy-2-methoxy- 、 N-[[5-Chloro-2-(methylamino)phenyl]phenylmethylene]glycine Methyl Ester 、 2-甲氨基-5-氯二苯甲酮
  参考文献：
  名称：

  Mechanism of Alkaline Hydrolysis of Diazepam

  摘要：

  AbstractDiazepam (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‐l‐methyl‐5‐pheny]‐2H‐1,4‐benzodiazepine). The seven‐member diazepine ring of 7 opened at the N1‐C2 bond to form a glycinate [5, 2‐methylamino‐5‐chloro‐α‐(phenylhenzylidene)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.

  DOI：

  10.1002/jccs.199800044