(R)-3-bromo-1-phenoxy-2-propanol | 140630-35-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R)-3-bromo-1-phenoxy-2-propanol
• 英文别名: (2R)-1-bromo-3-phenoxypropan-2-ol
• CAS: 140630-35-9
• 化学式: C₉H₁₁BrO₂
• 分子量: 231.089
• InChiKey: HWHIPBPKAGDPBM-QMMMGPOBSA-N

物化性质

• 沸点：
  329.7±27.0 °C(Predicted)
• 密度：
  1.467±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-3-bromo-1-phenoxy-2-propanol 在 氢氧化钾 作用下， 以 乙醚 为溶剂， 生成 (S)-苯氧甲基环氧乙烷
  参考文献：
  名称：

  聚合物负载的手性 Co(Salen) 配合物：末端环氧化物水解动力学拆分的合成应用和机理研究

  摘要：

  本文介绍了聚苯乙烯和二氧化硅结合的手性 Co(salen) 配合物的合成及其在不对称催化中的应用。已经设计了将 salen 络合物共价连接到两种类型载体的通用方法，并且相应的固定化钴衍生物被证明是有效且高度对映选择性的催化剂，用于末端环氧化物的水解动力学拆分 (HKR)。这些系统为与从 HKR 中分离反应产物相关的某些技术难题提供了实用的解决方案。通过过滤和重复循环去除负载型催化剂被证明不会损失反应性或对映选择性。由该催化剂体系介导的酚对映选择性加成到末端环氧化物提供了一种简便的、相应对映体富集的芳醚的高产合成。固定化催化剂已适用于连续流动工艺，以在高温下生成反应产物...

  DOI：

  10.1021/ja984410n
• 作为产物：
  描述：

  1-bromo-3-phenoxy-propan-2-ol 生成 (R)-3-bromo-1-phenoxy-2-propanol
  参考文献：
  名称：

  Enzyme assisted preparation of enantiomerically pure β-adrenergic blockers II. Building blocks of high optical purity and their synthetic conversion

  摘要：

  Based on previous screening results a series of potential building blocks 2-4 for beta-adrenergic blockers were prepared both by enzymatic hydrolysis and acyltransfer and further transformed into the corresponding oxiranes and aminoalcohols of defined absolute configurations.

  DOI：

  10.1016/s0957-4166(00)80191-3

文献信息

• Asymmetric Catalytic Synthesis of α-Aryloxy Alcohols: Kinetic Resolution of Terminal Epoxides via Highly Enantioselective Ring-Opening with Phenols
  作者：Joseph M. Ready、Eric N. Jacobsen

  DOI：10.1021/ja9910917

  日期：1999.6.1

  terminal epoxides with catalyst 3b4 (Scheme 1, Nu ) OH) suggested that (salen)Co(III) complexes might also serve as effective catalysts for the enantioselective addition of phenols to epoxides. This strategy has proven successful, and we report here the first examples of kinetic resolution of epoxides with phenols, with the isolation of 1-aryloxy 2-alcohols (1) in high ee’s and yields. Reaction of 2.2

  哈佛大学化学与化学生物学系，剑桥，马萨诸塞州 02138 接收日期：1999 年 4 月 6 日 对映纯的 R-芳氧基醇 (1) 是不对称合成的重要目标，因为它们在多种药学上重要的化合物中作为关键合成中间体。 1 原则上，可以通过多种途径获得这些结构单元，包括芳氧基酮的不对称还原 2 或对映纯末端环氧化物与酚类的开环。其中，后者可能是最通用和最直接的，但将酚类加成到环氧化物中的可用方法极其有限。尚未设计出用于末端环氧化物的酚类开环的催化方法，3 且未催化反应需要强制条件，例如在酚盐存在下在极性溶剂中加热环氧化物至高温。这些热方法通常产量低，特别不适合敏感基材。因此，尽管最近发现了获得高光学纯度末端环氧化物的通用方法 4，但通过环氧化物与酚类开环来开发对映纯 R-芳氧基醇的路线仍然是一个未解决的问题。外消旋形式的末端环氧化物的易接近性使得末端环氧化物与酚的动力学拆分成为一种潜在的有吸引力的途径
• Water content influences the selectivity of CALB-catalyzed kinetic resolution of phenoxymethyl-substituted secondary alcohols
  作者：Elisabeth Egholm Jacobsen、Thorleif Anthonsen

  DOI：10.1139/v02-068

  日期：2002.6.1

  Derivatives of 1-phenoxy-2-alkanols were kinetically resolved by esterification with irreversible and reversible acyl donors using lipase B from Candida antarctica (Novozyme 435) as a catalyst. To optimize the relative rate of reaction (the E-value), esterifications in eight different solvents with different water activities were performed. For 3-bromo-1-phenoxy-2-propanol (1), the E-values in all the solvents were higher when the water activity was increased, while the E-values for 1-phenoxy-2-pentanol (2) and 3-chloro-1-phenoxy-2-propanol (3) decreased by increasing water activity. The water content of the various reaction media with the same water activity was determined. Solvents such as 1,4-dioxane, acetonitrile, and tetrahydrofuran contained much more water than hexane, carbon tetrachloride, cyclohexane, toluene, and benzene. At high-water activity, the high-water content of the former group of solvents resulted in termination of the reaction at low conversion. The reason seemed to be that the acyl donor and possibly also the produced esters were hydrolyzed. This was not the case when the esterification was performed in water-immiscible solvents with the same water activity.Key words: kinetic resolution, E-value, solvents, water activity, water content.

  1-苯氧基-2-烷醇的衍生物通过使用来自南极酵母(Candida antarctica，Novozyme 435)的脂肪酶B作为催化剂，通过与不可逆和可逆酰基供体酯化来进行动力学分辨。为了优化反应的相对速率（E值），在具有不同水活性的八种不同溶剂中进行了酯化反应。对于3-溴-1-苯氧基-2-丙醇（1），当水活性增加时，所有溶剂中的E值都更高，而对于1-苯氧基-2-戊醇（2）和3-氯-1-苯氧基-2-丙醇（3），随着水活性的增加，E值降低。确定了具有相同水活性的各种反应介质的含水量。1,4-二噁烷、乙腈和四氢呋喃等溶剂含水量比己烷、四氯化碳、环己烷、甲苯和苯更多。在高水活性下，前一组溶剂的高含水量导致在低转化率时终止反应。原因似乎是酰基供体，可能也是产生的酯被水解。当在具有相同水活性的不相溶水溶剂中进行酯化反应时，情况并非如此。关键词：动力学分辨，E值，溶剂，水活性，含水量。
• Highly enantioselective CALB-catalyzed kinetic resolution of building blocks for β-blocker atenolol
  作者：Ingvild T. Lund、Pål L. Bøckmann、Elisabeth E. Jacobsen

  DOI：10.1016/j.tet.2016.02.018

  日期：2016.11

  Both enantiomers of 4-(3-chloro-2-hydroxypropoxy)phenyl)acetamide has been synthesized in 98.5–99% enantiomeric excess by use of lipase B from Candida antarctica as catalyst. The R-alcohol is a building block for the cardioselective β-blocker (S)-atenolol ((S)-2-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide. Performing kinetic resolutions of 3-chloro-1-phenoxy-2-propanol and 3-bromo-1-phenoxy-2-propanol

  使用南极假丝酵母的脂肪酶B作为催化剂，合成了4- （ 3-氯-2-羟基丙氧基）苯基）乙酰胺的两种对映体，其对映体过量为98.5-99％。的[R -醇是用于心脏选择性β受体阻滞剂（积木小号）-atenolol （（S） - 2 - （ 4 - （ 2 -羟基- 3 - （异丙基氨基）丙氧基）苯基）乙酰胺执行的3动力学拆分。 -氯-1-苯氧基-2-丙醇和3-溴-1-苯氧基-2-丙醇，丁酸乙烯酯为酰基供体，CALB酶相同，但制备方法不同，E值较高值比以前报告的值高。
• Enhanced selectivity in Novozym 435 catalyzed kinetic resolution of secondary alcohols and butanoates caused by the (R)-alcohols
  作者：Elisabeth Egholm Jacobsen、Erik van Hellemond、Anders Riise Moen、Lucia Camino Vazquez Prado、Thorleif Anthonsen

  DOI：10.1016/j.tetlet.2003.09.105

  日期：2003.11.10

  In esterifications of secondary alcohols catalyzed by immobilized lipase B from Candida antarctica (Novozym 435) the E-values decreased during the reaction. Hydrolysis of the corresponding butanoates showed the opposite effect. When an enantiopure (R)-alcohol, related but different, was added to the transesterification reaction, the E-value was significantly enhanced.

  在固定化来自南极假丝酵母的脂肪酶B （Novozym 435）催化的仲醇的酯化反应中，E值降低。相应的丁酸酯的水解显示相反的作用。当将相关但不同的对映体（R）-醇加入酯交换反应中时，E-值显着提高。
• Immobilization does not influence the enantioselectivity of CAL-B catalyzed kinetic resolution of secondary alcohols
  作者：Elisabeth Egholm Jacobsen、Liv Siri Andresen、Thorleif Anthonsen

  DOI：10.1016/j.tetasy.2004.11.081

  日期：2005.2

  Decreasing enantioselectivity (E-value) by increasing conversion has been observed in transesterification reactions of secondary alcohols catalyzed by a pure protein formulation of lipase B from Candida antarctica (Novozym 525 F). Addition of a range of enantiopure alcohols caused a temporary increase in selectivity of the transesterification reaction of 3-chloro-1-phenoxy-2-propanol with vinyl butanoate. The corresponding immobilized lipase B, (Novozym 435) showed a similar relationship between the E-value and degree of conversion. (C) 2004 Elsevier Ltd. All rights reserved.