4-(3’-trifluoromethylphenoxy)benzonitrile

• 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: 4-(3’-trifluoromethylphenoxy)benzonitrile
• 英文别名: 4-(3'-trifluoromethylphenoxy)benzonitrile；4-(3-trifluorophenoxy)benzonitrile；4-[3-(Trifluoromethyl)phenoxy]benzenecarbonitrile；4-[3-(trifluoromethyl)phenoxy]benzonitrile
• 化学式: C₁₄H₈F₃NO
• 分子量: 263.219
• InChiKey: QAEJDCVHJBSIKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 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：
  33
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3’-trifluoromethylphenoxy)benzonitrile 在 硫酸 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 12.0h， 生成 N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl}-2-methylpropyl]-4-[3-(trifluoromethyl)phenoxy]benzamide
  参考文献：
  名称：

  Discovery of N-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists

  摘要：

  There is continuing interest in the discovery and development of new kappa opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [S-35]GTP gamma S binding assay showed that neither compound showed the high potency and kappa opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [S-35]GTP gamma S binding stimulated by the selective kappa opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyll-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good kappa opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [S-35]GTP gamma S binding assay showed that several of the analogues were potent and selective kappa opioid receptor antagonists.

  DOI：

  10.1021/jm400275h
• 作为产物：
  描述：

  对氟苯腈 、 间三氟甲基苯酚 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 0.08h， 以86%的产率得到4-(3’-trifluoromethylphenoxy)benzonitrile
  参考文献：
  名称：

  Synthesis of Diaryl Ethers, Diaryl Sulfides, Heteroaryl Ethers and Heteroaryl Sulfides under Microwave Dielectric Heating

  摘要：

  本文描述了利用微波加热技术合成二芳基醚和硫化物的方法。该方法在芳基卤与缺电子酚或苯硫酚的SNAr反应中表现出快速、高效的特点。该方法的应用范围可扩展到含有羟基的六元杂环化合物，以及2-嘧啶硫醇与适度活化的芳基卤的反应，分别得到杂芳基醚和硫化物。目前方法的优势包括广泛的底物适用性、无需金属催化剂、产品分离简便以及高纯度。

  DOI：

  10.1055/s-2005-865321

文献信息

• Synthesis of Diaryl Ethers, Diaryl Sulfides, Heteroaryl Ethers and Heteroaryl Sulfides under Microwave Dielectric Heating
  作者：Quanrui Wang、Feng Li、Qingqing Meng、Huansheng Chen、Zhiming Li、Fenggang Tao

  DOI：10.1055/s-2005-865321

  日期：——

  This paper describes the synthesis of diaryl ethers and sulfides by utilizing microwave heating methodology. The methodology is shown to be rapid and efficient for the coupling of phenols or thiophenol with electron-deficient aryl halides through a SNAr reaction. The scope of the protocol can be expanded to six-membered heterocycles bearing a hydroxyl group as well as to the reaction of 2-pyrimidinethiol with mildly activated aryl halides, providing heteroaryl ethers and sulfides, respectively. The advantages of the present method include the wide substrate scope, the obviation of metal catalysts, ease of product isolation, and high purity of products.

  本文描述了利用微波加热技术合成二芳基醚和硫化物的方法。该方法在芳基卤与缺电子酚或苯硫酚的SNAr反应中表现出快速、高效的特点。该方法的应用范围可扩展到含有羟基的六元杂环化合物，以及2-嘧啶硫醇与适度活化的芳基卤的反应，分别得到杂芳基醚和硫化物。目前方法的优势包括广泛的底物适用性、无需金属催化剂、产品分离简便以及高纯度。
• Microwave-Assisted Synthesis of Diaryl Ethers without Catalyst
  作者：Feng Li、Quanrui Wang、Zongbiao Ding、Fenggang Tao

  DOI：10.1021/ol0346436

  日期：2003.6.1

  [GRAPHICS]Diaryl ethers have been prepared by direct coupling of phenols including those that bear a strong electron-attracting substituent to electron-deficient aryl halides through SNAr-based addition reactions with assistance of microwave irradiation in high to excellent yields within 5-10 min. No catalysts were required under our conditions.
• Chimeric derivatives of functionalized amino acids and α-aminoamides: Compounds with anticonvulsant activity in seizure models and inhibitory actions on central, peripheral, and cardiac isoforms of voltage-gated sodium channels
  作者：Robert Torregrosa、Xiao-Fang Yang、Erik T. Dustrude、Theodore R. Cummins、Rajesh Khanna、Harold Kohn

  DOI：10.1016/j.bmc.2015.04.014

  日期：2015.7

  Six novel 3 ''-substituted (R)-N-(phenoxybenzyl) 2-N-acetamido-3-methoxypropionamides were prepared and then assessed using whole-cell, patch-clamp electrophysiology for their anticonvulsant activities in animal seizure models and for their sodium channel activities. We found compounds with various substituents at the terminal aromatic ring that had excellent anticonvulsant activity. Of these compounds, (R)-N-4'-((3 ''-chloro) phenoxy) benzyl 2-N-acetamido-3-methoxypropionamide ((R)-5) and (R)-N-4'-((3 ''-trifluoromethoxy) phenoxy) benzyl 2-N-acetamido-3-methoxypropionamide ((R)-9) exhibited high protective indices (PI = TD50/ED50) comparable with many antiseizure drugs when tested in the maximal electroshock seizure test to mice (intraperitoneally) and rats (intraperitoneally, orally). Most compounds potently transitioned sodium channels to the slow-inactivated state when evaluated in rat embryonic cortical neurons. Treating HEK293 recombinant cells that expressed hNaV1.1, rNa(V)1.3, hNa(V)1.5, or hNa(V)1.7 with (R)-9 recapitulated the high levels of sodium channel slow inactivation. (C) 2015 Elsevier Ltd. All rights reserved.
• Discovery of <i>N</i>-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists
  作者：Chad M. Kormos、Chunyang Jin、Juan Pablo Cueva、Scott P. Runyon、James B. Thomas、Lawrence E. Brieaddy、S. Wayne Mascarella、Hernán A. Navarro、Brian P. Gilmour、F. Ivy Carroll

  DOI：10.1021/jm400275h

  日期：2013.6.13

  There is continuing interest in the discovery and development of new kappa opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [S-35]GTP gamma S binding assay showed that neither compound showed the high potency and kappa opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [S-35]GTP gamma S binding stimulated by the selective kappa opioid agonist U69,593. These studies led to N-[(1S)-1-[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyll-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good kappa opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [S-35]GTP gamma S binding assay showed that several of the analogues were potent and selective kappa opioid receptor antagonists.
• Discovery of Novel Isoxazoline Derivatives Containing Diaryl Ether against Fall Armyworms
  作者：Di Feng、Shang Wu、Biaobiao Jiang、Siqi He、Yuqin Luo、Fangyi Li、Baoan Song、Runjiang Song

  DOI：10.1021/acs.jafc.3c00824

  日期：2023.5.10

  frugiperda) with traditional insecticides. To solve this pending issue, a series of novel isoxazoline derivatives containing diaryl ether structures were designed and synthesized, and most of the target compounds exhibited excellent insecticidal activity. Based on the three-dimensional quantitative structure–activity relationship (3D-QSAR) model analysis, we further optimized the molecular structure with compound

  随着害虫抗药性的不断进化，传统杀虫剂防治秋粘虫（Spodoptera frugiperda ）是一个巨大的挑战。为了解决这一悬而未决的问题，设计合成了一系列含有二芳基醚结构的新型异恶唑啉衍生物，大多数目标化合物表现出优异的杀虫活性。基于三维定量构效关系（3D-QSAR）模型分析，我们进一步优化了分子结构，得到了化合物L35并测试了其活性。化合物L35 (LC 50 = 1.69 mg/L) 对草地夜蛾表现出优异的杀虫活性, 优于市售氟虫腈 (LC 50 = 70.78 mg/L) 和茚虫威 (LC 50 = 5.37 mg/L)。酶联免疫吸附试验表明，L35可以上调昆虫体内 GABA 的水平。此外，分子对接和转录组学结果也表明，化合物L35可能通过作用于GABA受体影响草地螽斯的神经系统。值得注意的是，通过高效液相色谱法（HPLC），我们能够得到化合物L35的两种对映体，杀虫活性测试表明S