1-methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole
• 英文别名: 1-methyl-5-phenyl-3-trifluoromethyl-1H-pyrazole；1-Methyl-3-(trifluoromethyl)-5-phenylpyrazole；3-trifluoromethyl-1-methyl-5-phenylpyrazole；1-Methyl-3-(trifluoromethyl)-5-phenyl-1H-pyrazole；1-methyl-5-phenyl-3-(trifluoromethyl)pyrazole
• 化学式: C₁₁H₉F₃N₂
• 分子量: 226.201
• InChiKey: XYNCLEFNLBKFFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  丙烯酸丁酯 、 1-methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole 在 palladium diacetate 、 silver carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以75%的产率得到(E)-butyl 3-(1-methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)acrylate
  参考文献：
  名称：

  A new and direct route to 3-fluoromethyl substituted pyrazol-4-acrylates via Pd-catalyzed C–H activation

  摘要：

  Direct C4-H activation of 3-fluoromethyl pyrazoles followed by an oxidative coupling with acrylates, which is perhaps the most direct method for the synthesis of 3-fluoromethyl substituted pyrazol-4-aciylates of biological interest, remains challenging. Here, the first example of the straightforward olefination via Pd-catalyzed C4-H activation of both C3-CF3 and C3-CF2H substituted pyrazoles is reported. The reaction of various C3-CF3 substituted pyrazoles with acrylates proceeds smoothly in the presence of Pd(OAc)(2) and Ag2CO3, whereas olefination of C3-CF2H substituted pyrazoles requires the addition of benzoquinone. A further computational study reveals that reactivity of the pyrazolyl substrates employed are strongly impacted by the substituents of different nature on their C1 or C5 position, which is in good agreement with the experimental data. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.06.058
• 作为产物：
  描述：

  2-methyl-5-(trifluoromethyl)-1,2-dihydro-3H-pyrazol-3-one 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 1,1'-双(二苯基膦)二茂铁 、 potassium phosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 1-methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole
  参考文献：
  名称：

  Palladium-Catalyzed Coupling of Pyrazole Triflates with Arylboronic Acids

  摘要：

  A general protocol for the palladium-mediated Suzuki coupling reaction of pyrazole triflates and aryl boronic acids has been developed. The use of additional dppf ligand was determined to increase product yields allowing for the use of a broad range of reaction substrates.

  DOI：

  10.1021/jo0477897

文献信息

• Ambident polyfluoroalkyl-substituted pyrazoles in the methylation reactions
  作者：Anna E. Ivanova、Yanina V. Burgart、Viktor I. Saloutin、Pavel A. Slepukhin、Sophia S. Borisevich、Sergey L. Khursan

  DOI：10.1016/j.jfluchem.2017.01.009

  日期：2017.3

  good regioselectivity in the methylation of polyfluoroalkylpyrazoles was reached while varying the reaction conditions. Under basic conditions, methylation of such pyrazoles led to the preferred formation of 3-RF-pyrazoles, whereas the use of dimethyl sulfate in the absence of a base resulted in the predominant formation of 5-RF-pyrazoles. A proposed mechanism of methylation was discussed.

  已经使用量子化学计算来估计含多氟烷基的吡唑的反应性。在改变反应条件的同时，在多氟烷基吡唑的甲基化中具有良好的区域选择性。在碱性条件下，这种吡唑的甲基化导致优选形成3-R F-吡唑，而在不存在碱的情况下使用硫酸二甲酯导致主要形成5-R F-吡唑。讨论了拟议的甲基化机制。
• Improved Regioselectivity in Pyrazole Formation through the Use of Fluorinated Alcohols as Solvents: Synthesis and Biological Activity of Fluorinated Tebufenpyrad Analogs
  作者：Santos Fustero、Raquel Román、Juan F. Sanz-Cervera、Antonio Simón-Fuentes、Ana C. Cuñat、Salvador Villanova、Marcelo Murguía

  DOI：10.1021/jo800251g

  日期：2008.5.1

  The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity.
• Palladium-Catalyzed Coupling of Pyrazole Triflates with Arylboronic Acids
  作者：Curt A. Dvorak、Dale A. Rudolph、Sandy Ma、Nicholas I. Carruthers

  DOI：10.1021/jo0477897

  日期：2005.5.1

  A general protocol for the palladium-mediated Suzuki coupling reaction of pyrazole triflates and aryl boronic acids has been developed. The use of additional dppf ligand was determined to increase product yields allowing for the use of a broad range of reaction substrates.
• A new and direct route to 3-fluoromethyl substituted pyrazol-4-acrylates via Pd-catalyzed C–H activation
  作者：Xiaoguang Wang、Xiang Fang、Hongyuan Xiao、Dongming Gong、Xueyan Yang、Fanhong Wu

  DOI：10.1016/j.tet.2013.06.058

  日期：2013.8

  Direct C4-H activation of 3-fluoromethyl pyrazoles followed by an oxidative coupling with acrylates, which is perhaps the most direct method for the synthesis of 3-fluoromethyl substituted pyrazol-4-aciylates of biological interest, remains challenging. Here, the first example of the straightforward olefination via Pd-catalyzed C4-H activation of both C3-CF3 and C3-CF2H substituted pyrazoles is reported. The reaction of various C3-CF3 substituted pyrazoles with acrylates proceeds smoothly in the presence of Pd(OAc)(2) and Ag2CO3, whereas olefination of C3-CF2H substituted pyrazoles requires the addition of benzoquinone. A further computational study reveals that reactivity of the pyrazolyl substrates employed are strongly impacted by the substituents of different nature on their C1 or C5 position, which is in good agreement with the experimental data. (C) 2013 Elsevier Ltd. All rights reserved.