N-((1R,2R)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)cyclohexyl)-3,5-bis(trifluoromethyl)benzamide | 1251532-87-2

• 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: N-((1R,2R)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)cyclohexyl)-3,5-bis(trifluoromethyl)benzamide
• 英文别名: N-[(1R,2R)-2-[[3,5-bis(trifluoromethyl)phenyl]carbamothioylamino]cyclohexyl]-3,5-bis(trifluoromethyl)benzamide
• CAS: 1251532-87-2
• 化学式: C₂₄H₁₉F₁₂N₃OS
• 分子量: 625.481
• InChiKey: CXCXMKKWEZBIGD-QZTJIDSGSA-N

物化性质

• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  41
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  85.2
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N-((1R,2R)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)cyclohexyl)-3,5-bis(trifluoromethyl)benzamide 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以78%的产率得到N-((1R,2R)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)cyclohexyl)-3,5-bis(trifluoromethyl)benzothioamide
  参考文献：
  名称：

  A Dual-Catalysis Anion-Binding Approach to the Kinetic Resolution of Amines: Insights into the Mechanism via a Combined Experimental and Computational Study

  摘要：

  Racemic benzylic amines undergo kinetic resolution via benzoylation with benzoic anhydride in the presence of a dual catalyst system consisting of a readily available amide-thiourea catalyst and 4-dimethylaminopyridine (DMAP). An evaluation of various experimental parameters was performed in order to derive a more detailed understanding of what renders this process selective. The catalyst's aggregation behavior and anion-binding ability were evaluated in regard to their relevance for the catalytic process. Alternate scenarios, such as catalyst deprotonation or the in situ formation of a neutral chiral acylating reagent were ruled out. Detailed computational studies at the M06/6-31G(d,p) level of theory including solvent modeling utilizing a polarized continuum model provide additional insights into the nature of the ion pair and reveal a range of important secondary interactions that are responsible for efficient enantiodiscrimination.

  DOI：

  10.1021/jacs.5b00190
• 作为产物：
  描述：

  2,5-dioxopyrrolidin-1-yl 3,5-bis(trifluoromethyl)benzoate 、 N-[(1R,2R)-2-氨基环己基]-N'-[3,5-双(三氟甲基)苯基]硫脲 以 四氢呋喃 为溶剂， 以92%的产率得到N-((1R,2R)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)cyclohexyl)-3,5-bis(trifluoromethyl)benzamide
  参考文献：
  名称：

  Merging Nucleophilic and Hydrogen Bonding Catalysis: An Anion Binding Approach to the Kinetic Resolution of Propargylic Amines

  摘要：

  An efficient kinetic resolution of primary propargylic amines with s-factors of up to 56 is reported. The strategy is based on a dual catalytic approach, namely the use of a newly developed and easy-to-make thiourea-amide anion binding catalyst in combination with 4-(dimethylamino)pyridine (DMAP), both employed at a 5 mol% catalyst loading. Benzylic amines are also resolved with s-factors of up to 38.

  DOI：

  10.1021/ja105337h
• 作为试剂：
  描述：

  苯甲酰溴 、 α-苯乙胺 在 4-二甲氨基吡啶 、 N-((1R,2R)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)cyclohexyl)-3,5-bis(trifluoromethyl)benzamide 作用下， 以 甲苯 为溶剂， 反应 2.25h， 生成 (R)-(+)-N-苯甲酰-Alpha-甲基苯胺
  参考文献：
  名称：

  A Dual-Catalysis Anion-Binding Approach to the Kinetic Resolution of Amines: Insights into the Mechanism via a Combined Experimental and Computational Study

  摘要：

  Racemic benzylic amines undergo kinetic resolution via benzoylation with benzoic anhydride in the presence of a dual catalyst system consisting of a readily available amide-thiourea catalyst and 4-dimethylaminopyridine (DMAP). An evaluation of various experimental parameters was performed in order to derive a more detailed understanding of what renders this process selective. The catalyst's aggregation behavior and anion-binding ability were evaluated in regard to their relevance for the catalytic process. Alternate scenarios, such as catalyst deprotonation or the in situ formation of a neutral chiral acylating reagent were ruled out. Detailed computational studies at the M06/6-31G(d,p) level of theory including solvent modeling utilizing a polarized continuum model provide additional insights into the nature of the ion pair and reveal a range of important secondary interactions that are responsible for efficient enantiodiscrimination.

  DOI：

  10.1021/jacs.5b00190

文献信息

• A Dual-Catalysis Anion-Binding Approach to the Kinetic Resolution of Amines: Insights into the Mechanism via a Combined Experimental and Computational Study
  作者：Nisha Mittal、Katharina M. Lippert、Chandra Kanta De、Eric G. Klauber、Thomas J. Emge、Peter R. Schreiner、Daniel Seidel

  DOI：10.1021/jacs.5b00190

  日期：2015.5.6

  Racemic benzylic amines undergo kinetic resolution via benzoylation with benzoic anhydride in the presence of a dual catalyst system consisting of a readily available amide-thiourea catalyst and 4-dimethylaminopyridine (DMAP). An evaluation of various experimental parameters was performed in order to derive a more detailed understanding of what renders this process selective. The catalyst's aggregation behavior and anion-binding ability were evaluated in regard to their relevance for the catalytic process. Alternate scenarios, such as catalyst deprotonation or the in situ formation of a neutral chiral acylating reagent were ruled out. Detailed computational studies at the M06/6-31G(d,p) level of theory including solvent modeling utilizing a polarized continuum model provide additional insights into the nature of the ion pair and reveal a range of important secondary interactions that are responsible for efficient enantiodiscrimination.
• Merging Nucleophilic and Hydrogen Bonding Catalysis: An Anion Binding Approach to the Kinetic Resolution of Propargylic Amines
  作者：Eric G. Klauber、Chandra Kanta De、Tejas K. Shah、Daniel Seidel

  DOI：10.1021/ja105337h

  日期：2010.10.6

  An efficient kinetic resolution of primary propargylic amines with s-factors of up to 56 is reported. The strategy is based on a dual catalytic approach, namely the use of a newly developed and easy-to-make thiourea-amide anion binding catalyst in combination with 4-(dimethylamino)pyridine (DMAP), both employed at a 5 mol% catalyst loading. Benzylic amines are also resolved with s-factors of up to 38.