3-methoxy-3'-(trifluoromethyl)-1,1'-biphenyl | 352032-26-9

• 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: 3-methoxy-3'-(trifluoromethyl)-1,1'-biphenyl
• 英文别名: 3-methoxy-3'-(trifluoromethyl)biphenyl；3-methoxy-3'-trifluoromethylbiphenyl；1-methoxy-3-[3-(trifluoromethyl)phenyl]benzene
• CAS: 352032-26-9
• 化学式: C₁₄H₁₁F₃O
• 分子量: 252.236
• InChiKey: GEFKKPVLPNVXQE-UHFFFAOYSA-N

物化性质

• 沸点：
  305.0±42.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 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：

  3-methoxy-3'-(trifluoromethyl)-1,1'-biphenyl 在 氢碘酸 作用下， 反应 7.5h， 以82%的产率得到3'-(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：

  3-三氟甲基苯甲酸 在 四(三苯基膦)钯 、 tetrakis(acetonitrile)copper(I)tetrafluoroborate 、 lithium perchlorate 、 potassium carbonate 、 sodium fluoride 、 N-氟代双苯磺酰胺 作用下， 以 水 、 乙腈 为溶剂， 反应 18.0h， 生成 3-methoxy-3'-(trifluoromethyl)-1,1'-biphenyl
  参考文献：
  名称：

  铜电荷转移催化使（杂）芳基酸脱羧硼化和交叉偶联

  摘要：

  我们报告了一种用于芳基硼酸酯合成的铜催化策略，该策略利用光诱导配体到金属电荷转移 (LMCT) 将（杂）芳基酸转化为适合环境温度硼化的芳基自由基。这种近紫外过程在温和条件下发生，不需要对天然酸进行预功能化，并且广泛适用于各种芳基、杂芳基和药物底物。我们还报告了一种用于脱羧交叉偶联的一锅程序，该程序将催化 LMCT 硼酸化和钯催化的 Suzuki-Miyaura 芳基化、乙烯基化或与有机溴化物的烷基化结合起来，以获得一系列增值产品。通过开发异选择性双脱羧 C(sp 2 )–C(sp 2）偶联序列，铜催化的两种不同酸（包括药物底物）的 LMCT 硼化和卤化过程与随后的 Suzuki-Miyaura 交叉偶联配对。

  DOI：

  10.1021/jacs.2c01630

文献信息

• <i>N</i>-Heterocyclic Carbene Coordinated Heterogeneous Pd Nanoparticles as Catalysts for Suzuki–Miyaura Coupling
  作者：Hyemin Min、Hiroyuki Miyamura、Shū Kobayashi

  DOI：10.1246/cl.160369

  日期：2016.7.5

  Palladium nanoparticle (Pd NP) catalysts immobilized in a polymer with an N-heterocyclic carbene (NHC) moiety (PICB-NHC-Pd) have been developed, wherein the NHC moiety plays dual roles as a crosslinker and a ligand to activate the Pd NPs. The presence of both Pd NPs and NHC was confirmed by STEM/EDS and SR-MAS NMR analyses, respectively. This PICB-NHC-Pd catalyst showed excellent activity in the Suzuki–Miyaura

  已开发出固定在具有 N-杂环卡宾 (NHC) 部分 (PICB-NHC-Pd) 的聚合物中的钯纳米颗粒 (Pd NP) 催化剂，其中 NHC 部分起着交联剂和配体的双重作用以激活 Pd NP . 分别通过 STEM/EDS 和 SR-MAS NMR 分析证实了 Pd NPs 和 NHC 的存在。这种 PICB-NHC-Pd 催化剂在 Suzuki-Miyaura 偶联反应中表现出优异的活性，而不会浸出 Pd。在克级合成中获得了优异的结果，并且在不损失催化剂活性的情况下完成了催化剂回收/再利用实验。
• Aminoborylation/Suzuki–Miyaura tandem cross coupling of aryl iodides as efficient and selective synthesis of unsymmetrical biaryls
  作者：Ludovic Marciasini、Nicolas Richy、Michel Vaultier、Mathieu Pucheault

  DOI：10.1039/c1cc14605j

  日期：——

  Sequential borylation of a first aryl iodide using a dialkylaminoborane followed by a Suzuki-Miyaura cross coupling of second aryl iodide ended up with an efficient, selective and practical synthesis of unsymmetrical biaryls. This tandem coupling shows a wide range of applicability.

  使用二烷基氨基硼烷对第一芳基碘进行顺序硼化，然后对第二芳基碘进行Suzuki-Miyaura交叉偶联，最终实现了不对称联芳基的高效，选择性和实用合成。这种串联联接器显示出广泛的适用性。
• Efficient One-Pot Cross-Coupling of Two Aryl Halides by Stannylation/Stille Reaction in Water under Microwave Irradiation
  作者：Xin Tan、Zi Jie Zhou、Jia Xin Zhang、Xin Hong Duan

  DOI：10.1002/ejoc.201402404

  日期：2014.8

  and highly efficient one-pot approach has been developed for the Pd(PPh3)4-catalyzed cross-coupling of two different aryl or heteroaryl bromides/iodides. This method involves the combined use of microwave irradiation and water as a single solvent to achieve sequential stannylation and Stille cross-coupling reactions, which allows rapid access to a wide variety of biaryls in good to high yields. Furthermore

  一种简单高效的一锅法已被开发用于 Pd(PPh3)4 催化的两种不同芳基或杂芳基溴化物/碘化物的交叉偶联。该方法涉及组合使用微波辐射和水作为单一溶剂来实现顺序甲磺酰化和 Stille 交叉偶联反应，从而能够以良好到高产率快速获得各种联芳基化合物。此外，利用这种步骤经济的方案，2,5-二溴吡啶被反复二芳基化，并且啶酰菌胺中间体也以一锅法合成。
• Application of the ‘resin-capture–release’ methodology to macrocyclisation via intramolecular Suzuki–Miyaura coupling
  作者：Virginie Lobrégat、Gilles Alcaraz、Hugues Bienaymé、Michel Vaultier

  DOI：10.1039/b101156l

  日期：——

  Aryl boronic acids can be trapped by an ammonium hydroxide-form Dowex® Ion Exchangers resin (D-OH−) leading to polymer-ionically bound borates and cyclized, when properly designed, into macroheterocycles under Suzuki–Miyaura coupling conditions.

  芳基硼酸可以通过氨水基的Dowex®离子交换树脂（D-OH⁻）被捕获，导致聚合与离子结合的硼酸盐，并在适当设计下，在铃木－宫浦耦合条件下环化成宏观杂环结构。
• In situ Diazonium Salt Formation and Photochemical Aryl‐Aryl Coupling in Continuous Flow Monitored by Inline NMR Spectroscopy
  作者：Christoph Deckers、Thomas H. Rehm

  DOI：10.1002/chem.202303692

  日期：——

  for biphenyls are an underrated aryl radical source for the photochemical aryl-aryl coupling. This concept does not require any additional catalysts to perform an efficient and selective reaction. The photoarylation is supported by the application of Flow Chemistry using microreactors and modern LED technology. An integrated benchtop NMR spectrometer enables real-time analysis of the substituted products

  联苯的三氟乙酸重氮盐是用于光化学芳基-芳基偶联的被低估的芳基自由基源。这个概念不需要任何额外的催化剂来进行有效和选择性的反应。使用微反应器和现代 LED 技术的流动化学应用支持光芳基化。集成台式核磁共振波谱仪可以对替代产品进行实时分析。