Benzoic acid (1S,3aS,3bS,8R,10aR,10bS,12aS)-10a,12a-dimethyl-6-oxo-8-(toluene-4-sulfonyloxy)-hexadecahydro-6a-aza-benzo[3,4]cyclohepta[1,2-e]inden-1-yl ester | 138415-92-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Benzoic acid (1S,3aS,3bS,8R,10aR,10bS,12aS)-10a,12a-dimethyl-6-oxo-8-(toluene-4-sulfonyloxy)-hexadecahydro-6a-aza-benzo[3,4]cyclohepta[1,2-e]inden-1-yl ester
• 英文别名: [(1S,2R,5R,11S,12S,15S,16S)-2,16-dimethyl-5-(4-methylphenyl)sulfonyloxy-8-oxo-7-azatetracyclo[9.7.0.02,7.012,16]octadecan-15-yl] benzoate
• CAS: 138415-92-6
• 化学式: C₃₃H₄₁NO₆S
• 分子量: 579.758
• InChiKey: VTOHQJNTTSEYKB-SLSZACILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Benzoic acid (1S,3aS,3bS,8R,10aR,10bS,12aS)-10a,12a-dimethyl-6-oxo-8-(toluene-4-sulfonyloxy)-hexadecahydro-6a-aza-benzo[3,4]cyclohepta[1,2-e]inden-1-yl ester 在 silver nitrate 、 lithium chloride 作用下， 以 四氢呋喃 、 水 、 丙酮 、 叔丁醇 为溶剂， 反应 176.0h， 生成 Benzoic acid (1R,3aR,3bS,5aS,6S,8aS,8bS)-1-hydroxymethyl-3a,5a-dimethyl-11-oxo-hexadecahydro-11a-aza-indeno[5,4-e]azulen-6-yl ester
  参考文献：
  名称：

  A novel stereospecific rearrangement of 3-substituted B-homo-5-azasteroids to their A-nor analogs. Preparation, stereochemistry, and conformational studies

  摘要：

  The novel 3-alpha- and 3-beta-hydroxy-B-homo-5-azasteroid lactams 4 and 5 were prepared from testosterone. When the hydroxyl group in these compounds is converted into a leaving group, rearrangement to the corresponding A-nor azasteroids occurs under a variety of conditions, along with competing substitution with inversion of configuration at C-3. The rearrangements proceed with complete stereospecificity and are faster and more efficient in the 3-alpha-series. The observed stereochemistry, as well as the results of molecular modeling, low-temperature NMR, and X-ray crystallographic studies support a mechanism involving neighboring-group participation by the nitrogen atom in the departure of the nucleofuge from C-3 via the formation of aziridinium ion intermediates. Compounds in the 3-alpha-series require prior ring-flipping to the A-boat conformation, while those in the 3-beta-series react through the corresponding A-chairs. The differences in the free energies of the A-boat and A-chair forms are greater in the 3-beta-compounds (1.6-3.4 kcal/mol) than in the corresponding 3-alpha-isomers (0.1-1.3 kcal/mol). The 3-alpha-chloro derivative 19 exists mainly as the A-chair in solution (DELTA-G = 0.3 kcal/mole; DELTA-G* = 12.2 kcal/mol), but crystallizes in the A-boat conformation. Molecular modeling studies of several 3-substituted derivatives and X-ray investigations of 19 and its 3-beta-isomer 20 also reveal separate flip forms of the B-rings associated with the A-chair and A-boat conformations in each case. Relief of steric hindrance between one of the hydrogen atoms at C-19 and the beta-hydrogen at C-7 (this H-H contact is only 1.98 angstrom in the crystal structure of 19) in the A-boat conformations of the 3-alpha-series enhances anchimeric assistance to the departure of the leaving group and facilitates the rearrangements of these compounds relative to their 3-beta-counterparts.

  DOI：

  10.1021/jo00041a013
• 作为产物：
  描述：

  17β-hydroxy-4,5-secoandrost-3-yn-5-one 在 Lindlar's catalyst 吡啶 、 咪唑 、 喹啉 、 4-二甲氨基吡啶 、 盐酸羟胺 、 四丁基氟化铵 、 氢气 、 sodium hydride 、 溶剂黄146 、 对甲苯磺酰氯 、 间氯过氧苯甲酸 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 氯仿 为溶剂， 65.0 ℃ 、101.33 kPa 条件下， 反应 87.0h， 生成 Benzoic acid (1S,3aS,3bS,8R,10aR,10bS,12aS)-10a,12a-dimethyl-6-oxo-8-(toluene-4-sulfonyloxy)-hexadecahydro-6a-aza-benzo[3,4]cyclohepta[1,2-e]inden-1-yl ester
  参考文献：
  名称：

  A novel stereospecific rearrangement of 3-substituted B-homo-5-azasteroids to their A-nor analogs. Preparation, stereochemistry, and conformational studies

  摘要：

  The novel 3-alpha- and 3-beta-hydroxy-B-homo-5-azasteroid lactams 4 and 5 were prepared from testosterone. When the hydroxyl group in these compounds is converted into a leaving group, rearrangement to the corresponding A-nor azasteroids occurs under a variety of conditions, along with competing substitution with inversion of configuration at C-3. The rearrangements proceed with complete stereospecificity and are faster and more efficient in the 3-alpha-series. The observed stereochemistry, as well as the results of molecular modeling, low-temperature NMR, and X-ray crystallographic studies support a mechanism involving neighboring-group participation by the nitrogen atom in the departure of the nucleofuge from C-3 via the formation of aziridinium ion intermediates. Compounds in the 3-alpha-series require prior ring-flipping to the A-boat conformation, while those in the 3-beta-series react through the corresponding A-chairs. The differences in the free energies of the A-boat and A-chair forms are greater in the 3-beta-compounds (1.6-3.4 kcal/mol) than in the corresponding 3-alpha-isomers (0.1-1.3 kcal/mol). The 3-alpha-chloro derivative 19 exists mainly as the A-chair in solution (DELTA-G = 0.3 kcal/mole; DELTA-G* = 12.2 kcal/mol), but crystallizes in the A-boat conformation. Molecular modeling studies of several 3-substituted derivatives and X-ray investigations of 19 and its 3-beta-isomer 20 also reveal separate flip forms of the B-rings associated with the A-chair and A-boat conformations in each case. Relief of steric hindrance between one of the hydrogen atoms at C-19 and the beta-hydrogen at C-7 (this H-H contact is only 1.98 angstrom in the crystal structure of 19) in the A-boat conformations of the 3-alpha-series enhances anchimeric assistance to the departure of the leaving group and facilitates the rearrangements of these compounds relative to their 3-beta-counterparts.

  DOI：

  10.1021/jo00041a013

文献信息

• A novel stereospecific rearrangement of 3-substituted B-homo-5-azasteroid lactams to A-nor analogues
  作者：Thomas G. Back、Joseph H.-L. Chau、Jacek W. Morzycki

  DOI：10.1016/0040-4039(91)80208-n

  日期：1991.11

  B-Homo-5-azasteroid lactams containing nucleofugal substituents in the 3-position ( and ) undergo rearrangement via stereospecific ring contractions to afford A-nor analogues and .

  B-Homo-5-氮杂甾体内酰胺在3位（和）中含有futanical取代基，并通过立体特异性环收缩进行重排，以提供A-nor类似物和。
• A novel stereospecific rearrangement of 3-substituted B-homo-5-azasteroids to their A-nor analogs. Preparation, stereochemistry, and conformational studies
  作者：Thomas G. Back、Joseph H. L. Chau、Penelope W. Codding、Patricia L. Gladstone、David H. Jones、Jacek W. Morzycki、Aleksander W. Roszak

  DOI：10.1021/jo00041a013

  日期：1992.7

  The novel 3-alpha- and 3-beta-hydroxy-B-homo-5-azasteroid lactams 4 and 5 were prepared from testosterone. When the hydroxyl group in these compounds is converted into a leaving group, rearrangement to the corresponding A-nor azasteroids occurs under a variety of conditions, along with competing substitution with inversion of configuration at C-3. The rearrangements proceed with complete stereospecificity and are faster and more efficient in the 3-alpha-series. The observed stereochemistry, as well as the results of molecular modeling, low-temperature NMR, and X-ray crystallographic studies support a mechanism involving neighboring-group participation by the nitrogen atom in the departure of the nucleofuge from C-3 via the formation of aziridinium ion intermediates. Compounds in the 3-alpha-series require prior ring-flipping to the A-boat conformation, while those in the 3-beta-series react through the corresponding A-chairs. The differences in the free energies of the A-boat and A-chair forms are greater in the 3-beta-compounds (1.6-3.4 kcal/mol) than in the corresponding 3-alpha-isomers (0.1-1.3 kcal/mol). The 3-alpha-chloro derivative 19 exists mainly as the A-chair in solution (DELTA-G = 0.3 kcal/mole; DELTA-G* = 12.2 kcal/mol), but crystallizes in the A-boat conformation. Molecular modeling studies of several 3-substituted derivatives and X-ray investigations of 19 and its 3-beta-isomer 20 also reveal separate flip forms of the B-rings associated with the A-chair and A-boat conformations in each case. Relief of steric hindrance between one of the hydrogen atoms at C-19 and the beta-hydrogen at C-7 (this H-H contact is only 1.98 angstrom in the crystal structure of 19) in the A-boat conformations of the 3-alpha-series enhances anchimeric assistance to the departure of the leaving group and facilitates the rearrangements of these compounds relative to their 3-beta-counterparts.