N-(2-硝基苯基)-4-三氟甲基苯甲酰胺 | 161266-16-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(2-硝基苯基)-4-三氟甲基苯甲酰胺
• 英文名称: N-(2-nitrophenyl)-4-trifluoromethylbenzamide
• 英文别名: 4-trifluoromethyl-2'-nitrobenzanilide；N-(2-nitrophenyl)-4-(trifluoromethyl)benzamide
• CAS: 161266-16-6
• 化学式: C₁₄H₉F₃N₂O₃
• 分子量: 310.232
• InChiKey: RICLYUZOYXXYKA-UHFFFAOYSA-N

物化性质

• 沸点：
  335.5±42.0 °C(Predicted)
• 密度：
  1.452±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2-硝基苯基)-4-三氟甲基苯甲酰胺 在 二氢吡啶 、 10% palladium on activated carbon 作用下， 以 溶剂黄146 为溶剂， 反应 15.0h， 以99%的产率得到2-(4-trifluoromethyl-phenyl)-1H-benzoimidazole
  参考文献：
  名称：

  苯并恶唑和苯并咪唑的简便高效合成：Hantzsch 酯 1,4-二氢吡啶在还原环化反应中的应用

  摘要：

  苯并恶唑和苯并咪唑都是具有生物活性和药用意义的化合物中常见的杂环支架。邻位取代硝基苯衍生物的还原环化为苯并恶唑或苯并咪唑环的形成提供了一条有吸引力的途径。不幸的是，仅报道了几种通过邻硝基化合物还原环化的合成方法，并且产率相当低。在合成有用的有机转化中仿生还原剂的继续开发中，Hantzsch 酯 1,4-二氢吡啶 (HEH)，NAD(P)H 的类似物，引起了相当多的关注。因此，我们希望报告可以通过邻位取代的硝基苯衍生物与 Pd/C 催化的 HEH 反应有效合成苯并恶唑和苯并咪唑。一系列功能化的邻硝基苯基酯或邻硝基苯基酰胺被 HEH 有效还原并环化为相应的苯并恶唑或苯并咪唑。特别是，在相同取代基的存在下工作，相对于相应的苯并恶唑，可以以更高的产率获得苯并咪唑。此外，在目前的工作中，对 Pd/C 的回收进行了研究，结果表明在五次运行中仍能保持其高催化活性。根据我们的实验结果和 DFT 计算，提出

  DOI：

  10.1002/ejoc.201000985
• 作为产物：
  描述：

  4-三氟甲基苯甲酰氯 、 2-硝基苯胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以40%的产率得到N-(2-硝基苯基)-4-三氟甲基苯甲酰胺
  参考文献：
  名称：

  Cyclooxygenase-1-Selective Inhibitors Are Attractive Candidates for Analgesics That Do Not Cause Gastric Damage. Design and in Vitro/in Vivo Evaluation of a Benzamide-Type Cyclooxygenase-1 Selective Inhibitor

  摘要：

  Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable to COX-1-inhibitory activity or other bioactivities. Here, we report that N-(5-amino-2-pyridinyl)-4(trifluoromethyl)benzamide (18f, TFAP), which has a structure clearly different from those of currently available COX-1-selective inhibitors, is a potent COX-1-selective inhibitor (COX-1IC(50) = 0.80 +/- 0.05 mu M, COX-2IC(50) = 210 I mu M). This compound causes little gastric damage in rats even at an oral dose of 300 mg/kg, though it has an analgesic effect at as low a dose as 10 mg/kg. Our results show that COX-1-selective inhibitors can be analgesic agents without causing gastric damage.

  DOI：

  10.1021/jm701191z

文献信息

• An Effective Method for Acylation of Weakly Nucleophilic Anilines with Silyl Carboxylates via Mixed Anhydrides
  作者：Mitsutomo Miyashita、Isamu Shiina、Teruaki Mukaiyama

  DOI：10.1246/bcsj.67.210

  日期：1994.1

  In the presence of a catalytic amount of active titanium(IV) salt generated in situ from 1 mol of TiCl4 and 2 mol of AgOTf, weakly nucleophilic anilines react under mild conditions with nearly equimolar amounts of silyl carboxylates to afford the corresponding anilides in excellent yields using 4-(trifluoromethyl)benzoic anhydride. The mixed anhydride formed in situ from trimethylsily acetate and 4-(trifluoxomethyl)benzoic anhydride, a key intermediate of this reaction, was detected by 1H NMR experiment. Further, it was shown that the reaction of the mixed anhydrides and 2-nitroaniline was faster than that of the corresponding homo anhydrides and 2-nitroaniline.

  在由1摩尔TiCl4和2摩尔AgOTf原位生成的催化量活性钛(IV)盐存在下，弱亲核性苯胺在温和条件下与几乎等摩尔量的硅基羧酸盐反应，使用4-(三氟甲基)苯甲酸酐，以优异的产率得到相应的苯胺酰胺。通过1H NMR实验检测到由三甲基硅基乙酸酯和4-(三氟甲氧基)苯甲酸酐原位形成的混合酐，这是该反应的关键中间体。进一步表明，混合酐与2-硝基苯胺的反应速率比相应的同系酐与2-硝基苯胺的反应速率更快。
• Shiina, Isamu; Miyashita, Mitsutomo; Nagai, Masashi, Heterocycles, 1995, vol. 40, # 1, p. 141 - 148
  作者：Shiina, Isamu、Miyashita, Mitsutomo、Nagai, Masashi、Mukaiyama, Teruaki

  DOI：——

  日期：——
• Miyashita Mitsutomo, Shiina Isamu, Mukaiyama Teruaki, Bull. Chem. Soc. Jap, 67 (1994) N 1, S 210-215
  作者：Miyashita Mitsutomo, Shiina Isamu, Mukaiyama Teruaki

  DOI：——

  日期：——
• Facile and Efficient Synthesis of Benzoxazoles and Benzimidazoles: The Application of Hantzsch Ester 1,4-Dihydropyridines in Reductive Cyclization Reactions
  作者：Rui-Guang Xing、Ya-Nan Li、Qiang Liu、Qing-Yuan Meng、Jing Li、Xiao-Xia Shen、Zhengang Liu、Bo Zhou、Xiaojun Yao、Zhong-Li Liu

  DOI：10.1002/ejoc.201000985

  日期：2010.12

  Both benzoxazole and benzimidazole are common heterocyclic scaffolds in biologically active and medicinally significant compounds. Reductive cyclization of ortho-substituted nitrobenzene derivatives provides an attractive route to benzoxazole or benzimidazole ring formation. Unfortunately, only a few synthetic methods by reductive cyclization of ortho-nitro compounds have been reported and the yields

  苯并恶唑和苯并咪唑都是具有生物活性和药用意义的化合物中常见的杂环支架。邻位取代硝基苯衍生物的还原环化为苯并恶唑或苯并咪唑环的形成提供了一条有吸引力的途径。不幸的是，仅报道了几种通过邻硝基化合物还原环化的合成方法，并且产率相当低。在合成有用的有机转化中仿生还原剂的继续开发中，Hantzsch 酯 1,4-二氢吡啶 (HEH)，NAD(P)H 的类似物，引起了相当多的关注。因此，我们希望报告可以通过邻位取代的硝基苯衍生物与 Pd/C 催化的 HEH 反应有效合成苯并恶唑和苯并咪唑。一系列功能化的邻硝基苯基酯或邻硝基苯基酰胺被 HEH 有效还原并环化为相应的苯并恶唑或苯并咪唑。特别是，在相同取代基的存在下工作，相对于相应的苯并恶唑，可以以更高的产率获得苯并咪唑。此外，在目前的工作中，对 Pd/C 的回收进行了研究，结果表明在五次运行中仍能保持其高催化活性。根据我们的实验结果和 DFT 计算，提出
• Cyclooxygenase-1-Selective Inhibitors Are Attractive Candidates for Analgesics That Do Not Cause Gastric Damage. Design and in Vitro/in Vivo Evaluation of a Benzamide-Type Cyclooxygenase-1 Selective Inhibitor
  作者：Hiroki Kakuta、Xiaoxia Zheng、Hiroyuki Oda、Shun Harada、Yukio Sugimoto、Kenji Sasaki、Akihiro Tai

  DOI：10.1021/jm701191z

  日期：2008.4.1

  Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable to COX-1-inhibitory activity or other bioactivities. Here, we report that N-(5-amino-2-pyridinyl)-4(trifluoromethyl)benzamide (18f, TFAP), which has a structure clearly different from those of currently available COX-1-selective inhibitors, is a potent COX-1-selective inhibitor (COX-1IC(50) = 0.80 +/- 0.05 mu M, COX-2IC(50) = 210 I mu M). This compound causes little gastric damage in rats even at an oral dose of 300 mg/kg, though it has an analgesic effect at as low a dose as 10 mg/kg. Our results show that COX-1-selective inhibitors can be analgesic agents without causing gastric damage.