1-(4-methoxyphenyl)-5-phenyl-3-(trifluoromethyl)-1H-pyrazole | 586333-22-4

• 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-(4-methoxyphenyl)-5-phenyl-3-(trifluoromethyl)-1H-pyrazole
• 英文别名: 3-(trifluoromethyl)-1-(4-methoxyphenyl)-5-phenyl-1H-pyrazole；5-(4-methoxyphenyl)-1-phenyl-3-trifluoromethylpyrazole；1-(4-Methoxyphenyl)-5-phenyl-3-(trifluoromethyl)pyrazole
• CAS: 586333-22-4
• 化学式: C₁₇H₁₃F₃N₂O
• 分子量: 318.298
• InChiKey: FSRWGGJHLUEBHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-methoxyphenyl)-5-phenyl-3-(trifluoromethyl)-1H-pyrazole 、 丙烯酸丁酯 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77%的产率得到(E)-butyl 3-(1-(4-methoxyphenyl)-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：

  苯乙炔 在 正丁基锂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 24.0h， 生成 1-(4-methoxyphenyl)-5-phenyl-3-(trifluoromethyl)-1H-pyrazole
  参考文献：
  名称：

  3-或5-CF 3-吡唑的选择性，无金属方法：CF 3-壬酮与肼的溶剂转换反应

  摘要：

  对三氟乙酰化乙炔与芳基（烷基）肼的反应进行了详细的研究，目的在于区域选择性合成3-或5-三氟甲基化的吡唑。发现反应的区域选择性极大地取决于溶剂性质。高极性质子溶剂（六氟异丙醇）有利于3-三氟甲基吡唑的形成。相反，当反应在极性非质子溶剂（DMSO）中进行时，优先观察到它们的5-CF 3-取代的异构体的形成。或者，3-CF 3的区域选择性组装取代的吡唑可以通过两步一锅法进行。在酸性催化剂存在下三氟甲基化的炔酮与芳基（烷基）肼的反应导致形成相应的。后者可以通过用碱处理平滑地转化为3-CF 3-吡唑。该溶剂可切换程序用于制备重要药物，如Celebrex和SC-560以及其以克为单位的异构体。讨论了可能的反应机理。

  DOI：

  10.1021/acs.joc.7b00774

文献信息

• Synthesis of 1,3,5-Trisubstituted [4-<i>tert</i>-Butyl 2-(5,5-difluoro-2,2-dimethyl-6-vinyl-1,3-dioxan-4-yl)acetate]pyrazoles via a Pd-Catalyzed CH Activation
  作者：Xiaoguang Wang、Xiang Fang、Xueyan Yang、Meng Ni、Fanhong Wu

  DOI：10.1002/cjoc.201201100

  日期：2012.12

  The gem‐difluoromethylenated acetonide 2 was efficiently synthesized as new precursor of HMG‐CoA reductase inhibitor. Straightforward olefination via Pd‐catalyzed C4‐H activation of 1,3,5‐trisubstituted pyrazoles 1 was proceeded smoothly in the presence of Pd(OAc)2 and AgCO3. This protocol has merits in terms of the improved atomic economy and prevention from the generation of by‐products.

  所述宝石-difluoromethylenated丙酮化合物2作为HMG-COA还原酶抑制剂的新的前体有效地合成。在Pd（OAc）2和AgCO 3的存在下，通过Pd催化的1,3,5-三取代的吡唑1的C 4 -H活化的直链烯烃化反应顺利进行。该协议在改善原子经济和防止副产物生成方面具有优势。
• Mild and Regioselective Synthesis of 3-CF₃ -Pyrazoles by the AgOTf-Catalysed Reaction of CF₃ -Ynones with Hydrazines
  作者：Maxim A. Topchiy、Daria A. Zharkova、Andrey F. Asachenko、Vasiliy M. Muzalevskiy、Vyacheslav A. Chertkov、Valentine G. Nenajdenko、Mikhail S. Nechaev

  DOI：10.1002/ejoc.201800208

  日期：2018.8.1

  heterocyclization reactions to selectively give 3‐CF3‐pyrazoles. AgOTf was found to be the catalyst of choice, and various 3‐CF3‐pyrazoles were formed in up to 99 % isolated yield with high regioselectivity. The reaction has a broad scope: 3‐CF3‐pyrazoles with alkyl and aryl substituents as well as different functional groups can be prepared by this approach. The known pyrazole drugs Celebrex® and SC‐560 were efficiently

  研究了三氟甲基化的炔酮与芳基（烷基）肼的金和银催化反应。（THD-Dipp）AuOTf和AgOTf的使用导致快速的杂环化反应，从而选择性生成3-CF 3-吡唑。发现AgOTf是选择的催化剂，并且以高达99％的分离产率和高区域选择性形成了各种3-CF 3-吡唑。该反应的范围很广：可以通过这种方法制备具有烷基和芳基取代基以及不同官能团的3-CF 3-吡唑。有效制备了已知的吡唑药物Celebrex®和SC‐560，以证明该方法的实用性。机理研究表明，该反应涉及作为主要中间体的半胱氨酸的形成。
• Solvent- and Transition Metal Catalyst-Dependent Regioselectivity in the [3+2] Cyclocondensation of Trifluoromethyl<i>-</i>α,β<i>-</i>ynones with Hydrazines: Switchable Access to 3- and 5-Trifluoromethylpyrazoles
  作者：Min-Tsang Hsieh、Sheng-Chu Kuo、Hui-Chang Lin

  DOI：10.1002/adsc.201400853

  日期：2015.3.9

  The regioselectivity of the [3+2] cyclocondensation of trifluoromethyl‐α,β‐ynones with hydrazines can be readily tuned to preferentially afford either 3‐ or 5‐trifluoromethylpyrazoles through variation of the reaction conditions. Under catalysis with copper(II) acetate (2.0 mol%), cyclocondensation proceeded smoothly to yield 3‐trifluoromethylpyrazoles with high regioselectivity. In contrast, when

  三氟甲基组成的[3 + 2]环化缩合反应中区域选择性- α，β - ynones与肼类可以容易地调谐到优先得到或者3-或通过反应条件的变化5- trifluoromethylpyrazoles。在乙酸铜（II）（2.0 mol％）的催化下，环缩反应顺利进行，得到具有高区域选择性的3-三氟甲基吡唑。相反，当反应在无催化剂的条件下在二甲基亚砜中进行时，主要观察到了5-三氟甲基吡唑的形成。
• Pyrazole formation: Examination of kinetics, substituent effects, and mechanistic pathways
  作者：Joseph C. Sloop、Brent Lechner、Gary Washington、Carl L. Bumgardner、W. David Loehle、William Creasy

  DOI：10.1002/kin.20316

  日期：2008.7

  Reaction kinetics for the condensation of 1,3-diketones 1a–o with selected arylhydrazines (aryl = Ph, 4-NO2Ph, 4-CH3OPh, and 2,4-diNO2Ph) was studied using 19F NMR spectroscopy. Product regioselectivity is modulated by reactant ratios, substituents, and acidity. Reaction rates were found to be influenced by substituents on the diketones and on phenylhydrazines as well as by acidity of the reaction

  使用 19F NMR 光谱研究了 1,3-二酮 1a-o 与选定的芳基肼（芳基 = Ph、4-NO2Ph、4-CH3OPh 和 2,4-diNO2Ph）缩合的反应动力学。产物的区域选择性受反应物比例、取代基和酸度的调节。发现反应速率受二酮和苯肼上的取代基以及反应介质酸度的影响，速率变化高达 1000 倍。确定了这些环化的 Hammett ρ 值。发现该反应在二酮和芳基肼中都是一级反应。吡唑形成的速率决定步骤随着 pH 值的变化而变化。提出了支持这些发现的机制细节和反应途径。© 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 370–383, 2008
• [3 + 2] Cycloaddition Reaction of Vinylsulfonium Salts with Hydrazonoyl Halides: Synthesis of Pyrazoles
  作者：Wen-Jing Luo、Xiuwen Liang、Maizhuo Chen、Ke-Hu Wang、Danfeng Huang、Junjiao Wang、Dong-Ping Chen、Yulai Hu

  DOI：10.1021/acs.joc.4c00910

  日期：2024.7.19

  [3 + 2] cycloaddition reaction between in situ generated nitrile imines from hydrazonoyl halides and vinylsulfonium salts is developed. The nitrile imines are demonstrated to be a new class of reaction partner for vinylsulfonium salts to conduct the [3 + 2] cycloaddition reaction. The process provides a concise and efficient method for the construction of pyrazole derivatives under mild reaction conditions

  开发了由腙酰卤和乙烯基锍盐原位生成的腈亚胺之间的有效[3 + 2]环加成反应。腈亚胺被证明是乙烯基锍盐进行[3 + 2]环加成反应的一类新型反应伙伴。该工艺为反应条件温和、底物范围广、产物收率好、区域选择性高的吡唑衍生物的构建提供了一种简洁高效的方法。