1-(4-chlorobenzyl)-4-methoxybenzene | 37155-52-5

• 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: 1-(4-chlorobenzyl)-4-methoxybenzene
• 英文别名: 1-chloro-4-(4-methoxybenzyl)benzene；4'-Chlor-4-methoxy-diphenyl-methan；1-chloro-4-[(4-methoxyphenyl)methyl]benzene
• CAS: 37155-52-5
• 化学式: C₁₄H₁₃ClO
• 分子量: 232.71
• InChiKey: OBQBEPHXUXRVLN-UHFFFAOYSA-N

物化性质

• 熔点：
  76-78 °C
• 沸点：
  170-175 °C(Press: 5 Torr)
• 密度：
  1.136±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  16
• 可旋转键数：
  3
• 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：
  1

反应信息

• 作为反应物：
  描述：

  1-(4-chlorobenzyl)-4-methoxybenzene 在 aluminum (III) chloride 、 potassium tert-butylate 、 sodium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 生成 苄氯贝特
  参考文献：
  名称：

  Benzylation of arenes with benzyl halides synergistically promoted by in situ generated superacid boron trifluoride monohydrate and tetrahaloboric acid

  摘要：

  To examine the assembly methodology of diarylmethanes, a benzylation of (hetero)arenes with benzyl halides has been developed and various diarylmethanes were furnished with yields of up to 98% and regioselectivities of up to >99%. The complexation of the by-product halogen hydride with BF3 center dot OEt2 generated the Bronsted acid BF3 center dot HX (HBF3X, X=Cl or Br) in situ to synergistically promote the benzylation. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.01.037
• 作为产物：
  描述：

  4-(4-氯苯甲酰基)苯甲醚 在 三乙基硅烷 、 三氟乙酸 作用下， 生成 1-(4-chlorobenzyl)-4-methoxybenzene
  参考文献：
  名称：

  Discovery of 4-[(2S)-2-{[4-(4-Chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic Acid (DG-051) as a Novel Leukotriene A4 Hydrolase Inhibitor of Leukotriene B4 Biosynthesis

  摘要：

  Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA(4)H) as a key target for the treatment of cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA(4)H. Ligand efficiency was followed throughout our structure-activity studies. As applied within the context of LTA(4)H inhibitor design, the chemistry team was able to design a potent compound 20 (DG-051) (K(d) = 26 nM) with high aqueous solubility (>30 mg/mL) and high oral bioavailability (>80% across species) that is currently undergoing clinical evaluation for the treatment of myocardial infarction and stroke. The structural biology-chemistry interaction described in this paper provides a sound alternative to conventional screening techniques. This is the first example of a gene-to-clinic paradigm enabled by a fragment-based drug discovery effort.

  DOI：

  10.1021/jm900838g

文献信息

• Nickel catalyzed deoxygenative cross-coupling of benzyl alcohols with aryl-bromides
  作者：Vinoth Kumar Chenniappan、Devin Peck、Ronald Rahaim

  DOI：10.1016/j.tetlet.2020.151729

  日期：2020.4

  nickel-catalyzed cross-electrophile coupling of benzyl alcohols with aromatic bromides has been developed. This deoxygenative cross-coupling occurs under mild reaction conditions at ambient temperature affording diarylmethanes, or 1,3-diarylpropenes from benzyl allyl alcohols. The system demonstrated good chemoselectivity tolerating an assortment of reactive functional groups.

  已经开发了镍催化的苄醇与芳族溴化物的亲电子交联。该脱氧交叉偶联在环境温度下在温和的反应条件下发生，从苄基烯丙醇得到二芳基甲烷或1，3-二芳基丙烯。该系统表现出良好的化学选择性，可耐受各种反应性官能团。
• Iodine-catalyzed disproportionation of aryl-substituted ethers under solvent-free reaction conditions
  作者：Marjan Jereb、Dejan Vražič

  DOI：10.1039/c3ob27267b

  日期：——

  iodine produced triphenylmethane and the corresponding aldehydes and ketones. The electron-donating substituents facilitated the reaction, while the electron-withdrawing groups retarded it; the difference in reactivity is not very high. Such an observation may be in favour of hydride transfer, predominantly from the less electron rich side of the ether with more stable carbocation formation. With the isotopic

  碘被证明是在无溶剂反应条件下芳基取代的醚歧化的有效催化剂。将各种取代的1,1,1'，1'-四芳基二甲基醚转化为相应的二芳基酮和二芳基甲烷衍生物。由I 2催化的4-甲氧基苯基取代的醚的转化也产生了单烷基化和二烷基化的Friedel-Crafts产品。用催化量的碘处理三苯甲基烷基和三苯甲基苄基醚三苯甲烷以及相应的醛和酮。供电子的取代基促进了反应，而吸电子基团阻止了该反应。反应性差异不是很大。这种观察可能有利于氢化物转移，主要是从醚的电子富集较少的一侧开始，具有更稳定的碳正离子形成。通过同位素研究，可以确定，大部分的C–H键断裂在速率确定步骤中发生，而羰基氧原子则起源于起始醚，而不是空气。转化是在空气和氩气下进行的，HI不是起作用的催化剂。
• Highly Active Catalyst for the Heterogeneous Suzuki−Miyaura Reaction:  Assembled Complex of Palladium and Non-Cross-Linked Amphiphilic Polymer
  作者：Yoichi M. A. Yamada、Koji Takeda、Hideyo Takahashi、Shiro Ikegami

  DOI：10.1021/jo034354v

  日期：2003.10.1

  An assembled insoluble catalyst, PdAS, prepared from palladium ((NH4)2PdCl4 (1)) and non-cross-linked amphiphilic copolymer poly(N-isopropylacrylamide-co-4-diphenylstyrylphosphine) (2) was developed. It was found that PdAS is an excellent catalyst for the Suzuki-Miyaura reaction on three points: (1) The use of 8 x 10(-7) to 5 x 10(-4) mol equiv of PdAS afforded the coupling products efficiently after

  开发了由钯（（NH4）2PdCl4（1））和非交联两亲共聚物聚（N-异丙基丙烯酰胺-co-4-二苯基苯乙烯基膦）（2）制备的组装的不溶催化剂PdAS。已发现，PdAS在以下三个方面是铃木-宫浦反应的优良催化剂：（1）使用8 x 10（-7）到5 x 10（-4）摩尔当量的PdAS在偶联后有效地提供了偶联产物简单的后处理，营业额高达1,250,000。（2）催化剂可重复使用多次而不会损失催化活性。（3）PdAS在任何反应介质（即水或水性或无水有机溶剂）中均显示出良好的稳定性。对PdAS的分析研究表明2中的膦与钯配位形成PdCl2（PPh2Ar）2物种。
• Palladium catalyzed ligand-free Suzuki cross-coupling reactions of benzylic halides with aryl boronic acids under mild conditions
  作者：B.P. Bandgar、Sampada V. Bettigeri、Jaywant Phopase

  DOI：10.1016/j.tetlet.2004.07.073

  日期：2004.9

  A highly efficient Suzuki cross-coupling reaction between benzylic halides and aryl boronic acids using palladium chloride as catalyst in acetone:water (3:1) as the solvent system has been developed. High yields of products, mild reaction conditions and short reaction times in the absence of ligand are important features of this method.

  在丙酮：水（3∶1）作为溶剂体系中，使用氯化钯作为催化剂，开发了苄基卤化物和芳基硼​​酸之间的高效铃木交叉偶联反应。该方法的重要特征是产物的高收率，温和的反应条件和在不存在配体的情况下较短的反应时间。
• Palladium-Catalysed Cross-Coupling of Benzylammonium Salts with Boronic Acids under Mild Conditions
  作者：Robert Phipps、Paul Türtscher、Holly Davis

  DOI：10.1055/s-0036-1588548

  日期：2018.2

  pathway for the putative benzyl-Pd(II) intermediate obtained upon oxidative addition and have optimised this to obtain fluorene in good yield. Herein, we give a full account of the development of the palladium­-catalysed cross-coupling of benzylammonium salts with boronic acids. A range of benzylamine-derived quaternary ammonium salts can be coupled with boronic acids under relatively mild conditions

  作为Bürgenstock专栏2017年有机化学中的未来之星的一部分发布 抽象的 在本文中，我们充分考虑了钯催化的苄基铵盐与硼酸的交叉偶联的发展。一系列苄胺衍生的季铵盐可以在相对温和的条件下与硼酸偶联。我们的优化确定了可用于在氯化物存在下在铵上进行化学选择性交联的配体。我们证明了分子内钯催化的C–H活化也是氧化加成后推定的苄基-Pd（II）中间体的可行途径，并对其进行了优化，从而以良好的收率获得了芴。 在本文中，我们充分考虑了钯催化的苄基铵盐与硼酸的交叉偶联的发展。一系列苄胺衍生的季铵盐可以在相对温和的条件下与硼酸偶联。我们的优化确定了可用于在氯化物存在下在铵上进行化学选择性交联的配体。我们证明了分子内钯催化的C–H活化也是氧化加成后推定的苄基-Pd（II）中间体的可行途径，并对其进行了优化，从而以良好的收率获得了芴。