4-(4-fluorophenyl)-2-oxo-5,6,7,8-tetrahydro-1H-quinoline-3-carbonitrile | 1393713-33-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(4-fluorophenyl)-2-oxo-5,6,7,8-tetrahydro-1H-quinoline-3-carbonitrile
• CAS: 1393713-33-1
• 化学式: C₁₆H₁₃FN₂O
• 分子量: 269.279
• InChiKey: LLGHOSYHWYFOGP-KCKQSJSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  [2-¹³C]-cyanoacetamide 、 2-(4-fluoro-benzoyl)cyclohexanone 在 三乙胺 作用下， 以 氘代二甲亚砜 为溶剂， 反应 144.0h， 以83%的产率得到1-(4-fluorophenyl)-3-oxo-5,6,7,8-tetrahydro-2H-isoquinoline-4-carbonitrile
  参考文献：
  名称：

  Regiochemistry of the Condensation of 2-Aroyl-cyclohexanones and 2-Cyanoacetamide: ¹³C-Labeling Studies and Semiempirical MO Calculations

  摘要：

  Hydroxy-aryl-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles represent interesting chemical scaffolds, but synthetic access to these compounds is limited. The reaction of 2-aroyl-cyclohexanones with 2-cyanoacetamide and base in ethanol has been reported to lead to the formation of the tetrahydroisoquinoline isomer. We show that depending on the electronic nature of the para-substituent on the aryl ring, formation of the regioisomeric tetrahydroquinoline isomer can significantly compete. The electron-donating or -withdrawing properties of the para-substituent of the aryl ring determines the ratio of product isomers. A series of 2-aroyl-cyclohexanones, with para-substituents ranging from electron-donating to electron-withdrawing, were reacted with [2-C-13]-cyanoacetamide. The product ratio and absolute regiochemistry were directly determined by quantitative C-13, HMBC, and NOESY NMR spectroscopy on the reaction mixtures. A clear relationship between the regioisomeric product ratio and the Hammett sigma values of the substituents is demonstrated. This is explained by the separate in situ yields, which reveal that the pathway leading to the tetrahydroquinoline regioisomer is significantly more sensitive toward the electronic nature of the para-substituent than the pathway leading to the tetrahydroisoquinoline. Semiempirical AM1 molecular orbital calculations on the starting electrophile 2-aroyl-cyclohexanone support a correlation between the energy of the LUMOs and the regioisomeric product ratio. Our results facilitate synthetic access to a range of these interesting synthetic intermediates.

  DOI：

  10.1021/jo301138w

文献信息

• Regiochemistry of the Condensation of 2-Aroyl-cyclohexanones and 2-Cyanoacetamide: ¹³C-Labeling Studies and Semiempirical MO Calculations
  作者：Oscar P. J. van Linden、Maikel Wijtmans、Luc Roumen、Lonneke Rotteveel、Rob Leurs、Iwan. J. P. de Esch

  DOI：10.1021/jo301138w

  日期：2012.9.7

  Hydroxy-aryl-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles represent interesting chemical scaffolds, but synthetic access to these compounds is limited. The reaction of 2-aroyl-cyclohexanones with 2-cyanoacetamide and base in ethanol has been reported to lead to the formation of the tetrahydroisoquinoline isomer. We show that depending on the electronic nature of the para-substituent on the aryl ring, formation of the regioisomeric tetrahydroquinoline isomer can significantly compete. The electron-donating or -withdrawing properties of the para-substituent of the aryl ring determines the ratio of product isomers. A series of 2-aroyl-cyclohexanones, with para-substituents ranging from electron-donating to electron-withdrawing, were reacted with [2-C-13]-cyanoacetamide. The product ratio and absolute regiochemistry were directly determined by quantitative C-13, HMBC, and NOESY NMR spectroscopy on the reaction mixtures. A clear relationship between the regioisomeric product ratio and the Hammett sigma values of the substituents is demonstrated. This is explained by the separate in situ yields, which reveal that the pathway leading to the tetrahydroquinoline regioisomer is significantly more sensitive toward the electronic nature of the para-substituent than the pathway leading to the tetrahydroisoquinoline. Semiempirical AM1 molecular orbital calculations on the starting electrophile 2-aroyl-cyclohexanone support a correlation between the energy of the LUMOs and the regioisomeric product ratio. Our results facilitate synthetic access to a range of these interesting synthetic intermediates.