3,3-dideuterio-7-chloro-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepine-2(3H)-one

• 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: 3,3-dideuterio-7-chloro-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepine-2(3H)-one
• 英文别名: [3-2H2]diazepam；7-Chloro-3,3-dideuterio-1-methyl-5-phenyl-1,4-benzodiazepin-2-one
• 化学式: C₁₆H₁₃ClN₂O
• 分子量: 286.729
• InChiKey: AAOVKJBEBIDNHE-KBMKNGFXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  地西泮 在 氘氧化钠 作用下， 以 氘代甲醇-d 为溶剂， 反应 0.5h， 生成 3,3-dideuterio-7-chloro-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepine-2(3H)-one
  参考文献：
  名称：

  Base-Catalyzed Keto-Enol Tautomerism of Diazepam

  摘要：

  AbstractThe hydrogens at 3‐position of diazepam, a frequently prescribed anxiolytic drug worldwide, undergo an efficient exchange with deuterium atoms in alkaline deuterated methanol. The position of deuterium exchange is confirmed by proton nuclear magnetic resonance and mass spectral analyses. A base‐catalyzed keto‐enol tautomerism is proposed to be responsible for the observed deuterium exchange. This finding has been applied to the preparation of tritium‐labeled diazepam in which only aromatic protons are labeled with tritium atoms. A tritium‐labeled diazepam lacking tritium atoms at 1 and 3 positions is valuable as a substrate for quantitative metabolism studies.

  DOI：

  10.1002/jccs.199700060

文献信息

• Axial-Selective H/D Exchange of Glycine-Derived 1<i>H</i>-Benzo[<i>e</i>][1,4]diazepin-2(3<i>H</i>)-ones: Kinetic and Computational Studies of Enantiomerization
  作者：Paul R. Carlier、Yang-Sheng Sun、Danny C. Hsu、Qiao-Hong Chen

  DOI：10.1021/jo1010608

  日期：2010.10.1

  Glycine-derived 1H-benzo[e][1,4]diazepin-2(3H)-ones (BZDs) 5d−g featuring C9- and N1- substitution exhibit enantiomerization barriers too high to be measured by 1H NMR coalescence experiments. To address this problem, we found that room-temperature H/D exchange of these compounds is remarkably selective, affording only the axial-d1 isotopomers. 1H NMR spectroscopy was then employed to measure the rate

  甘氨酸衍生的1 H-苯并[ e ] [1,4]二氮杂-2（3 H）-ones（BZDs）5d - g具有C9-和N1-取代基，表现出很高的对映异构势垒，无法通过1 H NMR聚结测定实验。为了解决这个问题，我们发现这些化合物的该室温H / d交换是非常有选择性的，得到仅轴向- d 1个同位素。然后采用1 H NMR光谱测量这些d 1的构象转化率-高温下的化合物。这些研究揭示了BZD所确定的最高对映异构体阻隔性（最高28 kcal / mol）。密度泛函理论计算结果与1.2 kcal / mol内的实验对映异构势垒相匹配。
• Synthesis of 3-deuterated diazepam and nordiazepam 4-oxides and their use in the synthesis of other 3-deuterated derivatives
  作者：Shen K. Yang、Ren Tang、Quan-Long Pu

  DOI：10.1002/(sici)1099-1344(199608)38:8<753::aid-jlcr890>3.0.co;2-n

  日期：1996.8

  The protons at 3-positions of diazepam 4-oxide and nordiazepam 4-oxide underwent an efficient deuterium exchange via keto-enol tautomerism in deuterated alkaline methanol. The 3-dideuterated 4-oxides were each used as a starting material to synthesize 3-monodeuterated oxazepam and its 3-acetate, 3-monodeuterated temazepam and its 3-acetate, and 3-dideuterated diazepam and nordiazepam.