3-(1-Methylindol-2-yl)-8-methyl-8-azabicyclo<3.2.1>octan-3-ol | 155509-78-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 3-(1-Methylindol-2-yl)-8-methyl-8-azabicyclo<3.2.1>octan-3-ol
• CAS: 155509-78-7
• 化学式: C₁₇H₂₂N₂O
• 分子量: 270.374
• InChiKey: FIBHTZKYCJAGJN-HALDLXJZSA-N

反应信息

• 作为反应物：
  描述：

  3-(1-Methylindol-2-yl)-8-methyl-8-azabicyclo<3.2.1>octan-3-ol 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以84%的产率得到3-(1-Methylindol-2-yl)-8-methyl-8-azabicyclo<3.2.1>oct-3-ene
  参考文献：
  名称：

  Abbreviated Ibogaine Congeners. Synthesis and Reactions of Tropan-3-yl-2- and -3-indoles. Investigation of an Unusual Isomerization of 2-Substituted Indoles Using Computational and Spectroscopic Techniques

  摘要：

  The syntheses of several N-methyltropan-3-ylindoles, designed as congeners of ibogaine, are described. The synthetic approach to N-methyltropan-3-yl-2-indole revealed that the tropanyl 3'-center was quite sensitive to acid-catalyzed epimerization. The carbocyclic analog, N-methyl-2-[bicyclo[3.2.1]-oct-3-anyl] indole, also underwent this rearrangement. However, N-methyltropan-3-yl-3-indole was insensitive to acid or base, even under more vigorous conditions. This simple isomerization is quite rare for 2-substituted indoles, especially for cases where the center of reaction is not additionally activated, and normally only takes place under extreme reaction conditions. The mechanism of this reaction was investigated using ab initio molecular orbital calculations, NMR spectroscopy and deuterium labeling studies. These results indicate that, in contrast to those previously obtained for more reactive 2-substituted indoles, the reaction can best be explained using a simple exchange mechanism involving the exocyclic enamine tautomer of the indole ring as an intermediate. The difference in reactivity is suggested to arise from a decrease in the relative energy of the exocyclic enamine tautomer due to the presence of increased strain in the endo bicyclic 2-substituent. The title compounds displayed modest pharmacological activity in a variety of biological assays.

  DOI：

  10.1021/jo00087a037
• 作为产物：
  描述：

  1-甲基吲哚 、 tropinone 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以29%的产率得到3-(1-Methylindol-2-yl)-8-methyl-8-azabicyclo<3.2.1>octan-3-ol
  参考文献：
  名称：

  Abbreviated Ibogaine Congeners. Synthesis and Reactions of Tropan-3-yl-2- and -3-indoles. Investigation of an Unusual Isomerization of 2-Substituted Indoles Using Computational and Spectroscopic Techniques

  摘要：

  The syntheses of several N-methyltropan-3-ylindoles, designed as congeners of ibogaine, are described. The synthetic approach to N-methyltropan-3-yl-2-indole revealed that the tropanyl 3'-center was quite sensitive to acid-catalyzed epimerization. The carbocyclic analog, N-methyl-2-[bicyclo[3.2.1]-oct-3-anyl] indole, also underwent this rearrangement. However, N-methyltropan-3-yl-3-indole was insensitive to acid or base, even under more vigorous conditions. This simple isomerization is quite rare for 2-substituted indoles, especially for cases where the center of reaction is not additionally activated, and normally only takes place under extreme reaction conditions. The mechanism of this reaction was investigated using ab initio molecular orbital calculations, NMR spectroscopy and deuterium labeling studies. These results indicate that, in contrast to those previously obtained for more reactive 2-substituted indoles, the reaction can best be explained using a simple exchange mechanism involving the exocyclic enamine tautomer of the indole ring as an intermediate. The difference in reactivity is suggested to arise from a decrease in the relative energy of the exocyclic enamine tautomer due to the presence of increased strain in the endo bicyclic 2-substituent. The title compounds displayed modest pharmacological activity in a variety of biological assays.

  DOI：

  10.1021/jo00087a037