1-甲氧基-3-[4-(三氟甲基)苯基]苯 | 122801-56-3

• 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: 1-甲氧基-3-[4-(三氟甲基)苯基]苯
• 英文名称: 3-methoxy-4'-(trifluoromethyl)-1,1'-biphenyl
• 英文别名: 3-methoxy-4'-(trifluoromethyl)biphenyl；1-methoxy-3-[4-(trifluoromethyl)phenyl]benzene
• CAS: 122801-56-3
• 化学式: C₁₄H₁₁F₃O
• 分子量: 252.236
• InChiKey: JDYWQUFNWCVWFV-UHFFFAOYSA-N

物化性质

• 熔点：
  156-157 °C(Solv: ethanol (64-17-5))
• 沸点：
  292.0±35.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-甲氧基-3-[4-(三氟甲基)苯基]苯 在 氢碘酸 作用下， 反应 2.0h， 以70%的产率得到4'-(trifluoromethyl)-[1,1'-biphenyl]-3-ol
  参考文献：
  名称：

  Cyclohexylcarbamic Acid 3‘- or 4‘-Substituted Biphenyl-3-yl Esters as Fatty Acid Amide Hydrolase Inhibitors:  Synthesis, Quantitative Structure−Activity Relationships, and Molecular Modeling Studies

  摘要：

  Fatty acid amide hydrolase (FAAH) is a promising target for modulating endocannabinoid and fatty acid ethanolamide signaling, which may have important therapeutic potential. We recently described a new class of O-arylcarbamate inhibitors of FAAH, including the cyclohexylcarbamic acid biphenyl-3-yl ester URB524 (half-maximal inhibitory concentration, IC50 = 63 nM), which have significant anxiolytic-like properties in rats. In the present study, by introducing a selected group of substituents at the meta and para positions of the distal phenyl ring of URB524, we have characterized structure-activity profiles for this series of compounds and shown that introduction of small polar groups in the meta position greatly improves inhibitory potency. Most potent in the series was the m-carbamoyl derivative URB597 (4i, IC50 = 4.6 nM). Furthermore, quantitative structure-activity relationship (QSAR) analysis of an extended set of meta-substituted derivatives revealed a negative correlation between potency and lipophilicity and suggested that small-sized substituents may undertake polar interactions with the binding pocket of the enzyme. Docking studies and molecular dynamics simulations, using the crystal structure of FAAH, indicated that the O-biphenyl scaffold of the carbamate inhibitors can be accommodated within a lipophilic region of the substrate-binding site, where their folded shape mimics the initial 10-12 carbon atoms of the arachidonyl moiety of anandamide (a natural FAAH substrate) and methyl arachidonyl fluorophosphonate (a nonselective FAAH inhibitor). Moreover, substituents at the meta position of the distal. phenyl ring can form hydrogen bonds with atoms located on the polar section of a narrow channel pointing toward the membrane-associated side of the enzyme. The structure-activity characterization reported here should help optimize the pharmacodynamic and pharmacokinetic properties of this class of compounds.

  DOI：

  10.1021/jm031140x
• 作为产物：
  描述：

  对氯三氟甲苯 在 potassium phosphate tribasic heptahydrate 、 XPhos Pd G2 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 乙醇 、 水 为溶剂， 反应 10.0h， 生成 1-甲氧基-3-[4-(三氟甲基)苯基]苯
  参考文献：
  名称：

  芳基氯化物的室温硼化和一锅两步硼化/Suzuki-Miyaura 交叉偶联反应†

  摘要：

  描述了一种高效的室温硼化芳基氯化物策略。利用 Buchwald 的第二代预成型催化剂，以高产率获得了适用于各种基材的硼酸酯。该方法还以一锅两步顺序的方式应用于铃木-宫浦交叉偶联反应，为从芳基氯化物直接合成联芳基化合物提供了一种简便易行的途径。

  DOI：

  10.1039/c8ra01381k

文献信息

• Electrochemical Synthesis of Biaryls via Oxidative Intramolecular Coupling of Tetra(hetero)arylborates
  作者：Arif Music、Andreas N. Baumann、Philipp Spieß、Allan Plantefol、Thomas C. Jagau、Dorian Didier

  DOI：10.1021/jacs.9b12300

  日期：2020.3.4

  scope, scalability and robustness of this unconventional catalyst-free transformation, leading to functional-ized biaryls and ultimately furnishing drug-like small molecules as well as late stage derivatization of natural compounds. In addition, the observed selectivity of the oxidative coupling reaction is related to the electronic structure of the TABs through quantum-chemical calculations and experimental

  我们在此报告了由三氟芳基硼酸钾的配体交换反应制备的不对称四（杂）芳基硼酸盐（TAB）的氧化电偶联促进的多功能、无过渡金属和无添加剂的（杂）芳基-芳基偶联反应。该方法利用电化学氧化的能力，补充了现有的有机硼工具箱。我们展示了这种非常规无催化剂转化的广泛范围、可扩展性和稳健性，导致功能化联芳并最终提供类药物小分子以及天然化合物的后期衍生化。此外，通过量子化学计算和实验研究，观察到的氧化偶联反应的选择性与 TAB 的电子结构有关。
• <i>meta</i> C–H Arylation of Electron-Rich Arenes: Reversing the Conventional Site Selectivity
  作者：Luo-Yan Liu、Jennifer X. Qiao、Kap-Sun Yeung、William R. Ewing、Jin-Quan Yu

  DOI：10.1021/jacs.9b07887

  日期：2019.9.18

  report the first catalytic system that effectively performs meta C-H arylation of a variety of alkoxy aromatics including 2,3-dihydrobenzofuran and chromane with exclusive meta site-selectivity, thus reversing the conventional site selectivity governed by native electronic effects. The identification of an effective ligand and modified norbornene (NBE-CO2Me), as well as taking advantage of the statistics

  在不使用导向基团的情况下控制 CH 活化的位点选择性仍然是一个重大挑战。虽然由相互排斥的吡啶型配体调节的 Pd(II) 催化剂已被证明有利于芳烃相对富电子的碳中心，但逆转选择性以有利于相对缺电子位置的钯化作用是不可能的。在这里，我们报告了第一个催化系统，该系统有效地对包括 2,3-二氢苯并呋喃和色烷在内的各种烷氧基芳烃进行间位 CH 芳基化，具有独特的间位选择性，从而逆转了由天然电子效应控制的传统位点选择性。有效配体和改性降冰片烯 (NBE-CO2Me) 的鉴定，
• Nickel-Catalyzed Cross-Coupling of Aryltrimethylammonium Iodides with Organozinc Reagents
  作者：Lan-Gui Xie、Zhong-Xia Wang

  DOI：10.1002/anie.201100683

  日期：2011.5.16

  Broad scope and good tolerance: An efficient cross‐coupling of aryltrimethylammonium iodide salts with aryl‐, methyl‐, and benzylzinc chlorides catalyzed by [Ni(PCy3)2Cl2] has been achieved (see scheme). The reaction involves cleavage of the CN bond and displays broad substrate scope and good functional group tolerance. NMP=N‐methylpyrrolidine.

  广泛的范围和良好的耐受性：[Ni（PCy 3）2 Cl 2 ]催化实现了芳基三甲基碘化碘盐与芳基，甲基和苄基氯化物的有效交叉偶联（参见方案）。该反应涉及CN键的裂解，并显示出较宽的底物范围和良好的官能团耐受性。NMP = N-甲基吡咯烷
• Nickel-Catalyzed Cross-Coupling of Arene- or Heteroarenecarbonitriles with Aryl- or Heteroarylmanganese Reagents through CCN Bond Activation
  作者：Ning Liu、Zhong-Xia Wang

  DOI：10.1002/adsc.201200369

  日期：2012.6.18

  The nickel‐catalyzed cross‐coupling reaction of arene‐ or heteroarenecarbonitriles with aryl‐ or heteroarylmanganese reagents via CCN bond activation has been developed. Both electron‐rich and electron‐deficient nitriles can be employed as the electrophilic substrates. The reaction tolerates a range of functional groups and aromatic heterocycles.

  的arene-或heteroarenecarbonitriles与芳基-或heteroarylmanganese试剂的镍-催化的交叉偶联反应通过Ç  CN键活化已经研制成功。富电子和缺电子的腈都可以用作亲电子底物。该反应容许一定范围的官能团和芳族杂环。
• A Ligand-Free Palladium-Catalyzed Cross-Coupling of Aryl Sulfinates with Aryl Bromides
  作者：Pat Forgione、Dirk Ortgies

  DOI：10.1055/s-0033-1339279

  日期：——

  A ligand-free Pd-catalyzed cross-coupling of aryl sulfinates with aryl bromides has been developed. A variety of aryl bromides and aryl sulfinates undergo this transformation to yield the desired biaryl in a practical and economical manner.

  已开发出无配体的 Pd 催化芳基亚磺酸酯与芳基溴化物的交叉偶联。各种芳基溴化物和芳基亚磺酸盐经历这种转化，以实用且经济的方式产生所需的联芳基。