(+/-)-N-Methylmorphinan-6-one | 81451-64-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: (+/-)-N-Methylmorphinan-6-one
• CAS: 81451-64-1；84415-60-1
• 化学式: C₁₇H₂₁NO
• 分子量: 255.36
• InChiKey: JWTUKQUXWFYBJS-IKGGRYGDSA-N

物化性质

• 沸点：
  399.2±42.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.55
• 重原子数：
  19.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  20.31
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (+/-)-N-Methylmorphinan-6-one 、 乙二醇 在 溴 作用下， 以50%的产率得到(1'S,9'R,10'R)-12'-bromo-17'-methylspiro[1,3-dioxolane-2,13'-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2,4,6-triene]
  参考文献：
  名称：

  A Convenient Synthesis of Δ7,8-Morphinan-6-one and Its Direct Oxidation to 14-Hydroxy-Δ7,8-morphinan-6-one

  摘要：

  Synthesis of Delta(7,8)-morphinan-6-one by Grewe cyclization and bromoketalization reaction as crucial steps is described. Introduction of a hydroxyl group at 14-position is demonstrated by direct oxidation with MnO2 in the presence of silica gel. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00280-9
• 作为产物：
  描述：

  (+/-)-2-<(1-phenyl-1H-tetrazol-5-yl)oxy> morphinan-6-one 在 palladium on activated charcoal 甲酸 、 氢气 作用下， 反应 2.0h， 生成 (+/-)-N-Methylmorphinan-6-one
  参考文献：
  名称：

  A Convenient Synthesis of Δ7,8-Morphinan-6-one and Its Direct Oxidation to 14-Hydroxy-Δ7,8-morphinan-6-one

  摘要：

  Synthesis of Delta(7,8)-morphinan-6-one by Grewe cyclization and bromoketalization reaction as crucial steps is described. Introduction of a hydroxyl group at 14-position is demonstrated by direct oxidation with MnO2 in the presence of silica gel. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00280-9

文献信息

• Synthesis of (−)- and (+)-2-hydroxy-6-keto-<i>N</i>-methylmorphinans, their <i>O</i>-methyl ethers, and 2-deoxy congeners
  作者：Helmut Schmidhammer、Arnold Brossi

  DOI：10.1139/v82-437

  日期：1982.12.15

  Bischler–Napieralski cyclization of the known phenylacetamide 1, followed by selective ether cleavage of the 3,4-dihydroisoquinoline 2 and sodium borohydride reduction, afforded the tetrahydroisoquinoline 4. Optical resolution of 4 with tartaric acid gave the optical isomers 4a,b, which were converted into the 6-ketomorphinans 9a,b and their O-methyl ethers 10a,b by the following reaction sequence: Birch reduction, N-formylation of the dihydro bases, Grewe cyclization, removal of the N-formyl protecting groups, reductive N-methylation, and O-methylation. The 2-deoxy congeners 12a,b were obtained from 9a,b by phenyltetrazolylation, and catalytic removal of the heterocyclic etherfunction. The (−)-enantiomer 12a obtained by this synthesis was identical with material prepared from natural morphine, and exhibited the high antinociceptive potency already reported.

  已知苯乙酰胺1经Bischler–Napieralski环化反应后，经过选择性醚解离生成3,4-二氢异喹啉2，再经过硼氢化钠还原，得到四氢异喹啉4。用酒石酸对4进行光学分离得到光学异构体4a,b，随后经过以下反应序列将其转化为6-酮吗啡烷9a,b及其O-甲基醚10a,b：桦木还原、二氢碱的N-甲酰化、Grewe环化、去除N-甲酰保护基、还原N-甲基化和O-甲基化。通过苯基四氮唑化反应和催化去除杂环醚功能，将9a,b转化为2-脱氧同分异构体12a,b。通过该合成方法得到的(−)-对映体12a与从天然吗啡制备的物质相同，并且展现出已报道的高抗痛性能。
• Amaravathi, M.; Kumari, I. Krishna; Pardhasaradhi, M., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1984, vol. 23, # 11, p. 1103 - 1105
  作者：Amaravathi, M.、Kumari, I. Krishna、Pardhasaradhi, M.

  DOI：——

  日期：——