methyl (+/-)-α-acetoxy-α-(4-methylphenyl)acetate | 136707-99-8

• 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: methyl (+/-)-α-acetoxy-α-(4-methylphenyl)acetate
• 英文别名: methyl α-acetoxy-p-tolylacetate；methyl 2-acetoxy-2-(4-methylphenyl)acetate；methyl 2-acetoxy-2-(p-tolyl)acetate；methyl (acetyloxy)(4-methylphenyl)acetate；methyl acetoxy(4-methylphenyl)acetate；methyl acetoxy(4-tolyl)acetate；Methyl 2-acetyloxy-2-(4-methylphenyl)acetate
• CAS: 136707-99-8
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: GRTYMTCAVBOQHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (+/-)-α-acetoxy-α-(4-methylphenyl)acetate 在 pig liver acetone 作用下， 以 乙醚 、 水 为溶剂， 反应 4.0h， 生成 Methyl (S)-2-hydroxy-2-(4-methylphenyl)acetate 、 (R)-(-)-methyl 2-hydroxy-2-p-tolylacetate
  参考文献：
  名称：

  手性α-芳基-α-羟基乙酸的合成：猪肝丙酮粉（PLAP）诱导的对映选择性水解的取代作用

  摘要：

  猪肝脏丙酮粉（PLAP）烷基α乙酰氧基α-arylacetates的催化的水解产生烷基（小号） - α -芳基- α -hydroxyacetates在23-80％对映体纯度。对映选择性取决于O-乙酰扁桃酸酯的酯基。芳环上的取代导致较差的选择性。PLAP仅水解乙酸酯基团，而发现酯官能团是完全完整的。

  DOI：

  10.1016/0040-4020(94)01105-9
• 作为产物：
  描述：

  对甲基苯甲醛 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 水 、 对甲苯磺酸 、 sodium hydrogensulfite 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 12.0h， 生成 methyl (+/-)-α-acetoxy-α-(4-methylphenyl)acetate
  参考文献：
  名称：

  脂肪酶PS-30催化的立体选择性酰化反应对扁桃酸酯的动力学拆分

  摘要：

  通过使用脂肪酶PS-30作为催化剂，已通过立体选择性酰化反应实现了一系列外消旋扁桃酸酯的动力学拆分。动力学对映体比率（E）的值达到197.5。简要讨论了取代基的作用。

  DOI：

  10.1016/j.tetlet.2014.02.095

文献信息

• Chemoenzymatic Preparation of Enantiomerically Enriched (<i>R</i>)‐(–)‐Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline
  作者：Marcin Poterała、Maciej Dranka、Paweł Borowiecki

  DOI：10.1002/ejoc.201700161

  日期：2017.4.26

  resolution of several racemic derivatives of mandelic acid methyl ester catalyzed by lipases from Pseudomonas fluorescens (Amano AK) or Burkholderia cepacia (Amano PS-C II and Amano PS-IM) has been achieved. A gram-scale lipase-mediated kinetic resolution approach has been developed that allows the facile synthesis of the corresponding methyl (R)-(–)-mandelates with excellent enantiomeric excesses (up to

  已经实现了由荧光假单胞菌 (Amano AK) 或洋葱伯克霍尔德菌 (Amano PS-C II 和 Amano PS-IM) 的脂肪酶催化的扁桃酸甲酯的几种外消旋衍生物的对映选择性拆分。已经开发出一种克级脂肪酶介导的动力学拆分方法，可以轻松合成相应的甲基 (R)-(–)-扁桃酸，具有出色的对映体过量（高达 > 99 % ee）和反应对映选择性（E 值高达到 >200）。用于治疗注意力缺陷多动障碍 (ADHD) 和发作性睡病的多巴胺能药物 pemoline 是通过在碱性条件下将制备的 (R)-(-)-扁桃酸甲酯与盐酸胍缩合，以 98% 的 ee 直接合成的。使适应。光学纯形式的所需 (R)-(+)-pemoline (> 从乙醇中重结晶两次后获得 99% ee)。然而，手性 HPLC 证实旋光性匹莫林在甲醇溶液中发生外消旋化。
• One-Portion Synthesis of 2-Acetoxy Carbonyl Compounds from Aldehydes by Using an Acetylated Masked Acyl Cyanide
  作者：Hisao Nemoto、Tomoyuki Kawamura、Kyoko Kitasaki、Kenji Yatsuzuka、Masaki Kamiya、Yasuko Yoshioka

  DOI：10.1055/s-0028-1088044

  日期：2009.5

  α-Acetoxy esters or amides were synthesized directly and in one portion from aldehydes and alcohols or amines by one-carbon homologation using a masked acyl cyanide reagent bearing an acetyl group. masked acyl cyanide - one-portion synthesis - 2-acetoxy esters - 2-acetoxy amides - umpolung

  使用带有乙酰基的带掩蔽的酰基氰化物试剂，通过一碳同源性，由醛，醇或胺直接和一部分地从醛，醇或胺中直接合成α-乙酰氧基酯或酰胺。 掩蔽的酰基氰化物-一份合成-2-乙酰氧基酯-2-乙酰氧基酰胺-umpolung
• Urea-Induced Acid Amplification: A New Approach for Metal-Free Insertion Chemistry
  作者：Erica D. Couch、Tyler J. Auvil、Anita E. Mattson

  DOI：10.1002/chem.201403283

  日期：2014.7.1

  α‐aryldiazoacetates in high yield. This methodology was found to be generally applicable to a broad substrate scope and presents a conceptually new approach for organocatalytic diazo insertion reactions. Mechanistic investigations suggest that the reaction pathway involves a urea‐induced protonation of the α‐aryldiazoester.

  事实证明，增强二氟硼酸脲的催化活性对于提高酸度α-芳基重氮乙酸酯的无金属OH和SH插入反应而言是必不可少的。发现该方法通常适用于广泛的底物范围，并且提出了用于有机催化重氮插入反应的概念上新的方法。机理研究表明，该反应途径涉及尿素诱导的α-芳基重氮酯的质子化。
• Synthesis of Arylglycine and Mandelic Acid Derivatives through Carboxylations of α-Amido and α-Acetoxy Stannanes with Carbon Dioxide
  作者：Tsuyoshi Mita、Masumi Sugawara、Hiroyuki Hasegawa、Yoshihiro Sato

  DOI：10.1021/jo202597p

  日期：2012.3.2

  Incorporation reactions of carbon dioxide (CO2) with N-Boc-alpha\-amido and a-acetoxy stannanes were developed using CsF as a mild tin activator. Monoprotected alpha-amido stannanes could be used, and the corresponding arylglycine derivatives were obtained in moderate-to-high yields under 1 MPa (10 atm) of CO2 pressure. alpha-Acetoxy stannanes also underwent carboxylation to afford mandelic acid derivatives in excellent yields under ambient CO2 pressure. Both transformations enabled the synthesis of alpha-tertiary and alpha-quaternary carboxylic acid derivatives. In addition, the chirality of (S)-N-tert-butylsulfonyl-alpha-amido stannanes was transferred with up to 90% inversion of configuration at 100 degrees C.
• Anodic oxidation of .alpha.-substituted p-xylenes. Electronic and stereoelectronic effects of .alpha.-substituents in the deprotonation of alkylaromatic radical cations
  作者：Enrico Baciocchi、Mario Mattioli、Roberta Romano、Renzo Ruzziconi

  DOI：10.1021/jo00025a036

  日期：1991.12

  The effect of alpha-substituents on the deprotonation rate from the benzylic position of alkylaromatic radical cations, k(CH2Z)/k(CH3), has been investigated by determining the intramolecular selectivity in the anodic oxidation in acetic acid of alpha-Z-substituted p-xylenes 1 (Z = H, OMe, OH, Me, tert-butyl, OAc, COOMe, CN), 5,6-dimethylindan 4 (R = H), and 2,2,5,6-tetramethylindan 4 (R = Me). Some oxidations induced by CAN have also been carried out. It has been found that, with the exception of when Z = tert-butyl, the deprotonation rate of I.+ is always faster from the CH2Z group than from the CH3 group, independently of the electron-donating or electron-withdrawing nature of Z. The electron-donating groups (OH, OMe, Me), however, exert a larger effect than the electron-withdrawing ones (COOMe, CN). The negligible deprotonation rate from CH2-t-Bu has been ascribed to stereoelectronic effects (the bulky tert-butyl group does not allow the C-H bonds to be collinear with the pi-system), the suggestion being nicely confirmed by the observation that the deprotonation rate from the position 1(3), relative to that from the 5(6)-methyl group, is almost identical in the radical cations of 4 (R = H and Me). The effect of the other alpha-substituents is mainly of electronic nature and has been rationalized on the basis of a variable transition-state structure for the deprotonation process. It is suggested that with +R groups most of the charge, in the transition state, has been transferred to the C(alpha)-H bond where it can be stabilized by the alpha-substituent. With electron-withdrawing groups less charge transfer has taken place and the rate-enhancing effects of these groups is ascribed to their capability to significantly decrease the strength of the C(alpha)-H bond.