4-(2H1)methylanisole | 82101-69-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(2H1)methylanisole
• 英文别名: 4-[D]methylanisole；1-methoxy-4-(methyl-d) benzene；1-deuteriomethyl-4-methoxy-benzene；4-deuteriomethyl-anisole；4-Deuteriomethyl-anisol；1-(Deuteriomethyl)-4-methoxybenzene
• CAS: 82101-69-7
• 化学式: C₈H₁₀O
• 分子量: 123.159
• InChiKey: CHLICZRVGGXEOD-MICDWDOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  4-(2H1)methylanisole 在 氢溴酸 作用下， 生成 4-(2H1)methylphenol
  参考文献：
  名称：

  A New Procedure for Deconvolution of Inter-/Intramolecular Intrinsic Primary and α-Secondary Deuterium Isotope Effects from Enzyme Steady-State Kinetic Data

  摘要：

  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.

  DOI：

  10.1021/ja984214g
• 作为产物：
  描述：

  1-甲氧基-4-(苯氧基甲基)苯 在 deuterated hypophosphorous acid 、 palladium 10% on activated carbon 、 sodium carbonate 作用下， 以 重水 为溶剂， 反应 1.5h， 生成 4-(2H1)methylanisole
  参考文献：
  名称：

  A convenient method for palladium-catalyzed reductive deuteration of organic substrates using deuterated hypophosphite in D₂O

  摘要：

  我们研究了一种使用氘化次亚磷酸酯作为氘源对有机底物进行氘化的简便方法。在氧化氘中的碳上钯存在下，芳香卤化物、烯烃、炔烃、环氧化物和 O-苄基衍生物等有机底物的转移氘化过程高效进行，并以极高的氘含量得到相应的氘化产物。

  DOI：

  10.1002/jlcr.3277

文献信息

• Room‐Temperature Palladium‐Catalyzed Deuterogenolysis of Carbon Oxygen Bonds towards Deuterated Pharmaceuticals
  作者：Wei Ou、Xudong Xiang、Ru Zou、Qing Xu、Kian Ping Loh、Chenliang Su

  DOI：10.1002/anie.202014196

  日期：2021.3.15

  Site‐specific incorporation of deuterium into drug molecules to study and improve their biological properties is crucial for drug discovery and development. Herein, we describe a palladium‐catalyzed room‐temperature deuterogenolysis of carbon–oxygen bonds in alcohols and ketones with D2 balloon for practical synthesis of deuterated pharmaceuticals and chemicals with benzyl‐site (sp3 C−H) D‐incorporation. The

  氘在药物分子中的位点特异性掺入以研究和改善其生物学特性对于药物发现和开发至关重要。本文中，我们描述了使用D 2球囊进行钯催化的室温醇和酮中碳-氧键的氘氘脱氢反应，用于实际合成氘化药物和带有苄基位点（sp 3 CH）D掺入的化学物质。这种脱氧氘化策略的亮点是温和的条件，宽广的范围，实用性和高化学选择性。为了能够直接使用D 2 O，电催化D 2 O分流适用于原位供应D 2一经请求。通过该系统，使用D 2 O以可持续和实用的方式证明了氘在布洛芬的代谢位置（苄基位）中的精确掺入。
• Reductive lithiation of arylalkyl methyl ethers
  作者：Ugo Azzena、Simonetta Carta、Giovanni Melloni、Alessandra Sechi

  DOI：10.1016/s0040-4020(97)10080-1

  日期：1997.11

  We have investigated the reductive cleavage of arylalkyl methyl ethers with an excess of lithium metal and a catalytic amount of naphthalene. The reaction proceeds regioselectively in the presence of various substituents on the aromatic ring, allowing access to a wide array of arylalkyl lithium derivatives, some of which are not easily accessible by conventional methods.

  我们已经研究了芳基烷基甲基醚与过量的锂金属和催化量的萘的还原裂解。该反应在芳族环上存在各种取代基的情况下区域选择性地进行，从而允许获得各种各样的芳基烷基锂衍生物，其中某些不易通过常规方法获得。
• A mild, general, and metal-free method for site-specific deuteration induced by visible light using D₂O as the source of deuterium atoms
  作者：Shuai Shi、Ruining Li、Liangming Rao、Zhankui Sun

  DOI：10.1039/c9gc04096j

  日期：——

  Visible light induced desulfurization–deuteration method was developed using D₂O as the source of deuterium atoms. This radical approach features mild conditions, broad substrate scope, highly efficient D-incorporation and excellent functional group compatibility.

  开发了一种可见光诱导的脱硫-氘化方法，使用D₂O作为氘原子的来源。这种基于自由基的方法具有温和的条件、广泛的底物范围、高效的氘掺入和优秀的官能团兼容性。
• 一种羧酸脱羧氘化制备氘代化合物的方法
  申请人：中国科学院大连化学物理研究所

  公开号：CN112939748B

  公开（公告）日：2022-11-01

  本发明涉及一种羧酸脱羧氘化制备氘代化合物的方法。该方法以羧酸化合物为原料，将其在氘水中将羧酸根的氢原子交换为氘原子后，经过光催化脱羧氘化的过程，以羧酸基团作为定位基团实现化合物的选择性氘化，制备氘代化合物。所述的反应过程如下所示，其中R1、R2和R3均选自烷基、芳香基、氢原子中的至少一种。本发明利用氘水/氘水与氘气作为氘源，不需要使用昂贵、有毒的氘源试剂，无需添加剂，反应条件温和，且底物适用范围广。
• The Deuterium Isotope Effect in the Side Chain Halogenation of Toluene¹
  作者：Kenneth B. Wiberg、Lynn H. Slaugh

  DOI：10.1021/ja01545a034

  日期：1958.6

  intramolecular deuterium isotope effect obtained in the side chain halogenation of toluene and some of its derivatives has been determined. Factors which decreased the energy of activation decrease the isotope effect. This observation may be interpreted by a consideration of the potential energy curves for the dissociation of reactants and products. The magnitude of the isotope effect is used as a criterion

  在甲苯及其部分衍生物的侧链卤化中获得的分子内氘同位素效应已经确定。降低活化能的因素会降低同位素效应。这一观察结果可以通过考虑反应物和产物离解的势能曲线来解释。同位素效应的大小被用作考虑在甲苯及其部分衍生物的侧链卤化中获得的分子内氘同位素效应的标准。决定某些卤化反应机理的因素。（授权）