p-methoxybenzyl-1,1-d₂ chloride | 53392-23-7

• 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: p-methoxybenzyl-1,1-d₂ chloride
• 英文别名: 4-methoxy-(1',1'-2H2)benzyl chloride；d₂-1-(chloromethyl)-4-methoxybenzene；p-Methoxyphenyl-chlormethan-d(2)；p-Methoxybenzyl-α,α-d2-chlorid；4-Methoxy-(methylen-²H2)-benzylchlorid；1-(chloro-dideuterio-methyl)-4-methoxy-benzene；1-[chloro(dideuterio)methyl]-4-methoxybenzene
• CAS: 53392-23-7
• 化学式: C₈H₉ClO
• 分子量: 158.596
• InChiKey: MOHYOXXOKFQHDC-NCYHJHSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.43
• 重原子数：
  10.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  9.23
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  p-methoxybenzyl-1,1-d₂ chloride 在 硼氘化锂 作用下， 生成 1-methoxy-4-(methyl-D3)-benzene
  参考文献：
  名称：

  Holland, Herbert L.; Brown, Frances M.; Conn, Morgan, Journal of the Chemical Society. Perkin transactions II, 1990, # 10, p. 1651 - 1655

  摘要：

  DOI：
• 作为产物：
  描述：

  4-甲氧基苯基-1,1-D2-甲醇 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 p-methoxybenzyl-1,1-d₂ chloride
  参考文献：
  名称：

  亲核取代反应中的同位素效应。四、改变α碳上的取代基对SN2过渡态结构的影响

  摘要：

  动力学研究、次级 α-氘动力学同位素效应、初级氯动力学同位素效应 (1)、通过改变亲核试剂中的取代基确定的哈米特 ρ 值和活化参数已用于确定过渡态的详细（相对）结构用于对位取代苄基氯和噻吩氧离子之间的 SN2 反应。还介绍了当对位取代的苄基化合物与带负电荷的亲核试剂反应时观察到的 U 形哈米特 ρ 图的基本原理。

  DOI：

  10.1139/v82-360

文献信息

• An acid-promoted novel skeletal rearrangement initiated by intramolecular ipso-Friedel–Crafts-type addition to 3-alkylidene indolenium cations
  作者：Takuya Yokosaka、Tetsuhiro Nemoto、Yasumasa Hamada

  DOI：10.1039/c2cc31699d

  日期：——

  An acid-promoted novel skeletal rearrangement is described. Using trifluoroacetic acid as the acid promoter, an intramolecular ipso-Friedel-Crafts-type addition of phenols to 3-alkylidene indolenium cations, formation of iminium cations through rearomatization of the spirocyclohexadienone units, and intramolecular Pictet-Spengler reaction proceeded sequentially, producing tricyclic indole derivatives

  描述了一种酸促进的新型骨骼重排。使用三氟乙酸作为酸促进剂，将分子内的ipso-Friedel-Crafts型酚添加到3-亚烷基吲哚阳离子中，通过螺环己二烯酮单元的重新芳构化形成亚胺阳离子，并依次进行分子内的Pictet-Spengler反应，从而生成三环吲哚衍生品。
• Structural Optimizations of Thieno[3,2-<i>b</i>]pyrrole Derivatives for the Development of Metabolically Stable Inhibitors of Chikungunya Virus
  作者：Kuan-Chieh Ching、Thi Ngoc Quy Tran、Siti Naqiah Amrun、Yiu-Wing Kam、Lisa F. P. Ng、Christina L. L. Chai

  DOI：10.1021/acs.jmedchem.7b00180

  日期：2017.4.13

  discovery of thieno[3,2-b]pyrrole 1b that displayed good antiviral activity against CHIKV infection in vitro. However, it has a short half-life in the presence of human liver microsomes (HLMs) (T1/2 = 2.91 min). Herein, we report further optimization studies in which potential metabolically labile sites on compound 1b were removed or modified, resulting in the identification of thieno[3,2-b]pyrrole 20 and

  Chikungunya病毒（CHIKV）是一种重新出现的载体传播的alpha病毒，目前尚无针对CHIKV的经过批准的有效抗病毒治疗。我们先前报道了噻吩并[3,2- b ]吡咯1b的发现，它在体外对CHIKV感染表现出良好的抗病毒活性。但是，它在人肝微粒体（HLM）存在下的半衰期很短（T 1/2 = 2.91分钟）。本文中，我们报告了进一步的优化研究，其中化合物1b上潜在的代谢不稳定位点被去除或修饰，从而鉴定了噻吩并[3,2- b ]吡咯20和吡咯并[2,3- d ]噻唑23c在HLM中具有高达17倍的代谢半衰期增加，并具有良好的体内药代动力学特性。化合物20不仅减缓了病毒RNA的产生，并显示出对其他α病毒和CHIKV分离株的广谱抗病毒活性，而且还显示出有限的细胞毒性作用（CC 50 > 100μM）。这些研究已经确定了两种化合物，它们有可能作为抗CHIKV感染的抗病毒药物进行进一步开发。
• A New Procedure for Deconvolution of Inter-/Intramolecular Intrinsic Primary and α-Secondary Deuterium Isotope Effects from Enzyme Steady-State Kinetic Data
  作者：William S. McIntire、E. Thomas Everhart、John C. Craig、Vladislav Kuusk

  DOI：10.1021/ja984214g

  日期：1999.6.1

  The A(2)B(2) flavocytochrome p-cresol methylhydroxylase (PCMH) from Pseudomonas putida oxidizes 4-methylphenol (p-cresol) to 4-hydroxybenzyl alcohol in a process requiring scission of an a-C-H bond with concomitant reduction of covalently bound FAD in each A subunit. Values of k(cat)/K were determined from steady-state kinetic data for the reactions of PCMH with the following substrates: 4-methylphenol, 4-(H-2(1))methylphenol, 4-(H-2(2))methylphenol, and 4-(H-2(3))methylphenol. A procedure was devised to extract the intrinsic primary deuterium and intrinsic alpha-secondary deuterium kinetic isotope effects from these values of k(cat)/K. The primary effect, P, is 6.71 +/- 0.08, and the secondary effect, S, is 1.013 +/- 0.014. The magnitudes of these effects are discussed in terms of an early or late transition state, hydrogen tunneling, coupled motion between the leaving and remaining hydrogens of the methyl group, and a H- expulsion mechanism versus a substrate radical mechanism versus a covalent substrate-FAD intermediate mechanism. The reaction of 4-ethylphenol with PCMH produces 4-vinylphenol and (-)-S-1-(4-hydroxyphenyl)ethanol (similar to 100% enantomeric excess). The evidence indicates that these are formed from a common intermediate, presumably a p-quinone methide. From the partition ratios for the formation of the alcohol and 4-vinylphenol from 4-ethylphenol, 4-(1',1'-H-2(2))ethylphenol, and 4-(2',2',2'-H-2(3))ethylphenol, the primary isotope effect for conversion of the p-quinone (2',2',2' 2H3)methide to 4-(2',2'-H-2(2))vinylphenol was estimated to be about 2, and the a-secondary isotope effect for conversion of p-quinone (1'-H-2(1))methide to 1-(4-hydroxyphenyl)-(1'-H-2(1))ethanol was found to be inverse (=0.83), as expected for sp(2) to sp(3) hybridization change at the alpha-carbon. Values of k(cat)/K were determined for 4-ethylphenol, R,S-(+/-)-4-(1'-H-2(1))ethylphenol (abbreviated R,S-D), S-(-)-4-(1'-H-2(1))ethylphenol (S-D), R-(+)4-(1'-H-2(1))ethylphenol (R-D), and 4-(1',1'-H-2(2))ethylphenol (D2). The (D2)(k(cat)/K) value was found to be 5.1-6.1, the same as determined in an earlier study. Unexpectedly, the values for (R,S-D)(k(cat)/K), (S-D)(k(cat)/K), and (R-D)(k(cat)/K) were all about the same (similar to 1.7), indicating that then is nearly an equal probability for pro-R or pro-S C-H bond scission. An apparent flux ratio for the pro-S path/pro-R path was estimated to be 0.78 +/- 0.02. The same procedure devised to determine values for P and S for 4-methylphenol was used to determine these values for the 4-ethylphenol reaction (commitment to catalysis = 0); P = 5.98 +/- 0.12 and S = 0.967 +/- 0.021. These values are essentially the same as those determined for 4-methylphenol. Thus, the chemical mechanisms for both substrates are assumed to be similar.
• HOLLAND, HERBERT L.;BROWN, FRANCES;M.;CONN, MORGAN, J. CHEM. SOC. PT 2. PERKIN TRANS.,(1990) N0, C. 1651-1655
  作者：HOLLAND, HERBERT L.、BROWN, FRANCES、M.、CONN, MORGAN

  DOI：——

  日期：——