(R)-(+)-2-hydroxy-2-phenylpropanenitrile | 169221-14-1

• 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: (R)-(+)-2-hydroxy-2-phenylpropanenitrile
• 英文别名: (2R)-2-phenyl-2-hydroxypropionitrile；(R)-2-hydroxy-2-phenylpropanenitrile；(2R)-2-hydroxy-2-phenylpropanenitrile
• CAS: 169221-14-1
• 化学式: C₉H₉NO
• 分子量: 147.177
• InChiKey: NGLPDXCYIUHTNP-VIFPVBQESA-N

物化性质

• 沸点：
  291.1±20.0 °C(Predicted)
• 密度：
  1.127±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-(+)-2-hydroxy-2-phenylpropanenitrile 在 盐酸 、 硫酸 作用下， 反应 24.5h， 生成 (5R)-5-Methyl-5-phenyl-1,3-oxazolidin-4-one
  参考文献：
  名称：

  Stereoselective Umpolung Reactions with MetalatedP-Chiral Cyanohydrin Phosphates—Enantioselective Synthesis of Tertiary Cyanohydrins

  摘要：

  AbstractWe present the first cyanohydrin derivative4that allows diastereoselective umpolung reactions. In4the OH group of the cyanohydrin is linked with a chiral phosphate, which can be removed hydrolytically after asymmetric synthesis. Cyclization of pseudoephedrine1dwith POCl3gave2d. This was followed by addition of racemic benzaldehyde cyanohydrin3to give the key intermediate4dwith complete retention of the configuration at phosphorus. Deprotonation of4d, followed by addition of a wide variety of electrophiles afforded the crystalline products5with high diastereomeric excesses (deup to 94%). High asymmetric induction was also achieved for the reaction of4−Li+with acyl halides, α‐bromoacetates, 2‐cycloalkenones, α,β‐unsaturated esters, and γ‐bromoacetates. Lewis acid assisted hydrolysis proceeded without racemization and gave high yields of ketone cyanohydrins6. From the ring‐opened chiral auxiliary7, optically pure pseudoephedrine1was readily recovered by acid hydrolysis. Optically pure (R) and (S) ketone cyanohydrins are now accessible in a very general strategy, which circumvents the substrate limitations of enzymatic synthesis.

  DOI：

  10.1002/chem.19970030815
• 作为产物：
  描述：

  扁桃腈 在 三异丙氧基氯化钛 、 N,N-二甲基丙烯基脲 、 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 3.67h， 生成 (R)-(+)-2-hydroxy-2-phenylpropanenitrile
  参考文献：
  名称：

  Stereoselective Umpolung Reactions with MetalatedP-Chiral Cyanohydrin Phosphates—Enantioselective Synthesis of Tertiary Cyanohydrins

  摘要：

  AbstractWe present the first cyanohydrin derivative4that allows diastereoselective umpolung reactions. In4the OH group of the cyanohydrin is linked with a chiral phosphate, which can be removed hydrolytically after asymmetric synthesis. Cyclization of pseudoephedrine1dwith POCl3gave2d. This was followed by addition of racemic benzaldehyde cyanohydrin3to give the key intermediate4dwith complete retention of the configuration at phosphorus. Deprotonation of4d, followed by addition of a wide variety of electrophiles afforded the crystalline products5with high diastereomeric excesses (deup to 94%). High asymmetric induction was also achieved for the reaction of4−Li+with acyl halides, α‐bromoacetates, 2‐cycloalkenones, α,β‐unsaturated esters, and γ‐bromoacetates. Lewis acid assisted hydrolysis proceeded without racemization and gave high yields of ketone cyanohydrins6. From the ring‐opened chiral auxiliary7, optically pure pseudoephedrine1was readily recovered by acid hydrolysis. Optically pure (R) and (S) ketone cyanohydrins are now accessible in a very general strategy, which circumvents the substrate limitations of enzymatic synthesis.

  DOI：

  10.1002/chem.19970030815

文献信息

• Investigation of Lewis Acid versus Lewis Base Catalysis in Asymmetric Cyanohydrin Synthesis
  作者：Michael North、Marta Omedes-Pujol、Courtney Williamson

  DOI：10.1002/chem.201001078

  日期：——

  undertaken. When Lewis acid catalysis is dominant, a significantly positive reaction constant is observed, whereas reactions dominated by Lewis base catalysis give much smaller reaction constants. [Ti(salen)O}2] was found to show the highest degree of Lewis acid catalysis, whereas two [VO(salen)X] (X=EtOSO3 or NCS) complexes both displayed lower degrees of Lewis acid catalysis. In the case of reactions

  可以通过路易斯酸和/或路易斯碱催化三甲基甲硅烷基氰化物向醛的不对称加成，所述路易斯酸和/或路易斯碱分别活化所述醛和三甲基甲硅烷基氰化物。从催化剂的结构并不总是显而易见的是路易斯酸或路易斯碱催化是占主导地位。为了在使用钛，钒和铝的塞伦络合物作为催化剂的背景下进行研究，进行了不对称氰醇合成的哈米特分析。当路易斯酸催化起主导作用时，观察到明显的正反应常数，而路易斯碱催化占主导的反应给出的反应常数小得多。发现[Ti（salen）O} 2 ]显示出最高的路易斯酸催化程度，而两个[VO（salen）X]（X = EtOSO 3或NCS）配合物均显示较低程度的路易斯酸催化作用。在[Al（salen）} 2 O]和三苯膦氧化物催化的反应情况下，观察到非线性哈米特图，这表明随着羰基化合物变得更多电子，机理随着路易斯碱催化作用的增加而改变。 -不足。这些结果表明，铝络合物/三苯基膦氧化物催化剂体系也应催化
• Hydrolase-Catalysed Preparation of Chiral α,α-Disubstituted Cyanohydrin Acetates
  作者：Jarle Holt、Isabel W. C. E. Arends、Adriaan J. Minnaard、Ulf Hanefeld

  DOI：10.1002/adsc.200700053

  日期：2007.6.4

  The enzymatic hydrolysis of esters of tertiary alcohols has long been a challenge. In particular their kinetic resolutions have virtually not been addressed. Here we describe the successful kinetic resolution of α,α-disubstituted cyanohydrin acetates, a type of protected tertiary alcohols that form particularly interesting building blocks in organic synthesis. Utilising Subtilisin A the hydrolysis reaction

  叔醇酯的酶促水解长期以来一直是一个挑战。尤其是它们的动力学分辨率实际上还未得到解决。在这里，我们描述了α，α-二取代的氰醇乙酸盐的成功动力学拆分，这是一种受保护的叔醇，在有机合成中形成特别有趣的结构单元。利用枯草杆菌蛋白酶A，水解反应是（S）-选择性的，而皱纹念珠菌脂肪酶是（R）-选择性的。利用这些可商购的酶，现在可以得到α，α-二取代的氰醇乙酸盐的两种对映体。
• Catalytic Asymmetric Synthesis of (S)-Acetophenone Cyanohydrin under High Pressure
  作者：Michael C.K Choi、S.S Chan、Kiyoshi Matsumoto

  DOI：10.1016/s0040-4039(97)01561-x

  日期：1997.9

  The first trimethylsilylcyanation of acetophenone to its (S)-cyanohydrin was accomplished with e.e. up to 60% in 93% yield at 0.8 GPa, using 0.01 eq. of a reuseable catalyst prepared from (S)-3,3-dimethyl-1,2,4-butanetriol and titanium isopropoxide. Reactions of 4′-substituted acetophenones to the corresponding cyanohydrins gave lower e.e. and yields. © 1997 Elsevier Science Ltd.

  苯乙酮的第一个三甲基甲硅烷基氰化为其（S）-氰醇的反应是使用0.01 eq。ee在0.8 GPa时，收率高达60％，收率93％。由（S）-3，3-二甲基-1，2，4-丁三醇和异丙醇钛制得的可重复使用的催化剂。4'-取代的苯乙酮与相应的氰醇的反应产生较低的ee和收率。©1997爱思唯尔科学有限公司。
• Synthesis of (R)-cyanohydrins by crude (R)-oxynitrilase-catalyzed reactions in micro-aqueous medium
  作者：Shiqing Han、Guoqiang Lin、Zuyi Li

  DOI：10.1016/s0957-4166(98)00177-3

  日期：1998.6

  In diisopropyl ether or ethyl acetate under micro-aqueous conditions, the enantioselective synthesis of (R) cyanohydrins from aldehydes and methyl ketones was studied using crude (R)-oxynitrilase prepared from almonds. This reaction system performed well over the temperature range of 4 degrees C to 30 degrees C. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Enzymatic synthesis of (R)-cyanohydrins by three (R)-oxynitrilase sources in micro-aqueous organic medium
  作者：Guoqiang Lin、Shiqing Han、Zuyi Li

  DOI：10.1016/s0040-4020(98)01160-0

  日期：1999.3

  The enantioselective synthesis of optically active (R)-cyanohydrins generated from several aromatic, heteroaromatic and aliphatic aldehydes and methyl ketones was carried out using almond. peach or loquat meal as (R)-oxynitrilase sources in diisopropyl ether under micro-aqueous conditions. The micro-aqueous reaction system, which is superior to the conventionally used water-organic biphase reaction system, performed well over the temperature range of 4 degrees C to 30 degrees C. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.