2-<2'-(phenylthio)ethyl>-2,3,4,5,6,7-hexahydro-1,5-methano-3-oxo-1H-azocino<4,3-b>indole | 137333-48-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-<2'-(phenylthio)ethyl>-2,3,4,5,6,7-hexahydro-1,5-methano-3-oxo-1H-azocino<4,3-b>indole
• 英文别名: 2-[2'-(phenylthio)ethyl]-2,3,4,5,6,7-hexahydro-1,5-methano-3-oxo-1H-azocino[4,3-b]indole；(1S,12R)-15-(2-phenylsulfanylethyl)-9,15-diazatetracyclo[10.3.1.02,10.03,8]hexadeca-2(10),3,5,7-tetraen-14-one
• CAS: 137333-48-3
• 化学式: C₂₂H₂₂N₂OS
• 分子量: 362.495
• InChiKey: JXHBTVUYNAOZOC-YWZLYKJASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  61.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1,2,3,4-tetrahydro-4-oxo-9-<(p-methoxyphenyl)sulfonyl>carbazole-2-acetic acid 在 sodium tetrahydroborate 、 sodium amalgam 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 19.5h， 生成 2-<2'-(phenylthio)ethyl>-2,3,4,5,6,7-hexahydro-1,5-methano-3-oxo-1H-azocino<4,3-b>indole
  参考文献：
  名称：

  Studies on the synthesis of Strychnos alkaloids. A new entry into the azocino[4,3-b]indole core structure and related studies

  摘要：

  Treatment of cyclohexanone-3-acetic acid with phenylhydrazine hydrochloride gave the tetrahydrocarbazole 7 (73%). The derived methyl ester 8 (99.6%) was oxidized to the 4-oxo compound 9 in 85% yield by treatment with DDQ/90% aqueous THF at 0-degrees-C. Treatment of 9 with NaH/DMF at 0-degrees-C followed by (p-methoxyphenyl)sulfonyl chloride gave 10 (81%). Hydrolysis of 10 using lithium hydroxide in aqueous THF gave the acid 11 (86%). The acid 11 was converted into the amide 12 by treatment with ethylchloroformate/NEt3/CH2Cl2 followed by aqueous NH4OH. The ketoamide 12 was exposed to NaBH4/MeOH/THF to give a single alcohol 13 (> 95%). Exposure of 13 to trifluoroacetic acid (cat)/CH2Cl2/0-20-degrees-C gave the azocino[4.3-b]indole core tetracyclic lactam 14 (90%). The amide 14 was reduced (BH3.THF) to give 21, which was directly acetylated (PhSCH2COCl) to give exocyclic amide 22. All attempts to close the C11-C12 bond only resulted in decomposition. Treatment of the acid 11 with EtO2CCl/Et3N followed by [2-(phenylthio)ethyl]amine gave the amide 24 (90%). Reduction of 24 using NaBH4 gave the alcohol 25 which upon exposure to CF3CO2H at room temperature cyclized to the tetracyclic amide 26 (96% overall). Oxidation of the sulfide 26 (m-CPBA) resulted in the diastereomeric sulfoxides 28. When the sulfoxides 28 were exposed to Pummerer conditions the only products that could be isolated were the (E)- and (Z)-vinyl sulfides 29 (72% and 25%, respectively). Similarly the dimethylthio acetal 33 was converted into the aldehyde 34 (100%). Treatment of 26 with POCl3/DMF gave 35 (90.8%) which was exposed to PhNHNH2/AcOH/AcONa to give the pyrazole 36 (85%). Attempts to close the E-ring via sulfoxides derived from either the pyrazole 36 or the oxazole 37 were unsuccessful. Treatment of the chloride 40 with KH/HN(SiMe3)2 in toluene resulted in a slow conversion into the 3-oxindole 44.

  DOI：

  10.1021/jo00027a016

文献信息

• Studies on the synthesis of Strychnos alkaloids. A new entry into the azocino[4,3-b]indole core structure and related studies
  作者：Philip Magnus、Nancy L. Sear、Chung S. Kim、Nigel Vicker

  DOI：10.1021/jo00027a016

  日期：1992.1

  Treatment of cyclohexanone-3-acetic acid with phenylhydrazine hydrochloride gave the tetrahydrocarbazole 7 (73%). The derived methyl ester 8 (99.6%) was oxidized to the 4-oxo compound 9 in 85% yield by treatment with DDQ/90% aqueous THF at 0-degrees-C. Treatment of 9 with NaH/DMF at 0-degrees-C followed by (p-methoxyphenyl)sulfonyl chloride gave 10 (81%). Hydrolysis of 10 using lithium hydroxide in aqueous THF gave the acid 11 (86%). The acid 11 was converted into the amide 12 by treatment with ethylchloroformate/NEt3/CH2Cl2 followed by aqueous NH4OH. The ketoamide 12 was exposed to NaBH4/MeOH/THF to give a single alcohol 13 (> 95%). Exposure of 13 to trifluoroacetic acid (cat)/CH2Cl2/0-20-degrees-C gave the azocino[4.3-b]indole core tetracyclic lactam 14 (90%). The amide 14 was reduced (BH3.THF) to give 21, which was directly acetylated (PhSCH2COCl) to give exocyclic amide 22. All attempts to close the C11-C12 bond only resulted in decomposition. Treatment of the acid 11 with EtO2CCl/Et3N followed by [2-(phenylthio)ethyl]amine gave the amide 24 (90%). Reduction of 24 using NaBH4 gave the alcohol 25 which upon exposure to CF3CO2H at room temperature cyclized to the tetracyclic amide 26 (96% overall). Oxidation of the sulfide 26 (m-CPBA) resulted in the diastereomeric sulfoxides 28. When the sulfoxides 28 were exposed to Pummerer conditions the only products that could be isolated were the (E)- and (Z)-vinyl sulfides 29 (72% and 25%, respectively). Similarly the dimethylthio acetal 33 was converted into the aldehyde 34 (100%). Treatment of 26 with POCl3/DMF gave 35 (90.8%) which was exposed to PhNHNH2/AcOH/AcONa to give the pyrazole 36 (85%). Attempts to close the E-ring via sulfoxides derived from either the pyrazole 36 or the oxazole 37 were unsuccessful. Treatment of the chloride 40 with KH/HN(SiMe3)2 in toluene resulted in a slow conversion into the 3-oxindole 44.