2-(1-hydroxy-2-chloroethyl)-thiophene | 49703-01-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: 2-(1-hydroxy-2-chloroethyl)-thiophene
• 英文别名: 2-chloro-1-(thiophen-2-yl)ethan-1-ol；2-chloro-1-(thiophen-2-yl)ethanol；2-chloro-1-thiophen-2-yl-ethanol；2-(α-Hydroxy-β-chlor-aethyl)-thiophen；2-Chloro-1-thiophen-2-ylethanol
• CAS: 49703-01-7
• 化学式: C₆H₇ClOS
• 分子量: 162.64
• InChiKey: KBXQOVVOIBVNLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  48.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(1-hydroxy-2-chloroethyl)-thiophene 在 lithium aluminium tetrahydride 、 phosphate buffer 、 偶氮二甲酸二异丙酯 、 dimethyl sulfide borane 、 immobilised lipase from Pseudomonas cepacia 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 异丙醚 、 水 为溶剂， 反应 48.0h， 生成 度洛西汀
  参考文献：
  名称：

  Chemoenzymatic synthesis of duloxetine and its enantiomer: lipase-catalyzed resolution of 3-hydroxy-3-(2-thienyl) propanenitrile

  摘要：

  An efficient and facile chemoenzymatic synthesis of duloxetine by lipase mediated resolution of 3-hydroxy-3-(2-thienyl)propanenitrile has been achieved. This process also describes an en antioconvergent synthesis of duloxetine via a Mitsunobu reaction. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(03)00945-6
• 作为产物：
  描述：

  2-氯乙酰噻吩 在 sodium tetrahydroborate 、 cerium(III) chloride 作用下， 以 甲醇 为溶剂， 以75%的产率得到2-(1-hydroxy-2-chloroethyl)-thiophene
  参考文献：
  名称：

  Solvent and in situ catalyst preparation impacts upon Noyori reductions of aryl-chloromethyl ketones: application to syntheses of chiral 2-amino-1-aryl-ethanols

  摘要：

  As part of medicinal chemistry efforts we found it necessary to develop general syntheses of highly enantiomerically enriched 1-aryl-2-chloroethanols and 1-aryl-2-methylaminoethanols. A survey of literature methods suggested that a truly general approach had not yet been reported, encouraging us to undertake the development of such a methodology. This study describes the design, development, and reduction to practice of a general synthesis of chiral 1-aryl-2-chloroethanols and the transformation of these entities to highly enantiomerically enriched 1-aryl-2-methylaminoethanols. Of particular importance were observations of the impact of solvent and the method of catalyst preparation on the yield and enantiomerical excess of chlorohydrins prepared via Noyori transfer hydrogenations of aryl-chloromethyl ketones. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2006.07.017

文献信息

• Synthesis of enantiopure chloroalcohols by enzymatic kinetic resolution
  作者：Robert M. Haak、Chiara Tarabiono、Dick B. Janssen、Adriaan J. Minnaard、Johannes G. de Vries、Ben L. Feringa

  DOI：10.1039/b613937j

  日期：——

  3-Alkenyl and heteroaryl chloroalcohols have been obtained in excellent enantiomeric excess (>99%) by enzymatic kinetic resolution using the haloalcohol dehalogenase HheC. Yields were close to the theoretical maximum for all substrates employed. Furthermore, the applicability of this methodology on multigram scale has been established.

  通过使用卤醇脱卤酶HheC进行酶促动力学拆分，成功获得了具有优异对映体过剩（>99%）的3-烯基和杂芳基氯醇。所有使用底物的产率均接近理论最大值。此外，该方法在大规模多克重应用中的适用性也得到了验证。
• Efficient synthesis of chlorohydrins using ClCH2MgCl·LiCl
  作者：Rodolfo H.V. Nishimura、Fabiano T. Toledo、João L.C. Lopes、Giuliano C. Clososki

  DOI：10.1016/j.tetlet.2012.10.132

  日期：2013.1

  The mixed lithium-magnesium carbenoid ClCH2MgCl center dot LiCl was easily generated in THF through the reaction of chloroiodomethane with i-PrMgCl-LiCl at -78 degrees C. This reagent reacts well with a number of aldehydes to give the corresponding chlorohydrins in good yields. (C) 2012 Elsevier Ltd. All rights reserved.
• Organomagnesium Based Flash Chemistry: Continuous Flow Generation and Utilization of Halomethylmagnesium Intermediates
  作者：Timo von Keutz、David Cantillo、C. Oliver Kappe

  DOI：10.1021/acs.orglett.0c02725

  日期：2020.10.2

  The generation of highly unstable chloromethylmagnesium chloride in a continuous flow reactor and its reaction with aldehydes and ketones is reported. With this strategy, chlorohydrins and epoxides were synthesized within a total residence time of only 2.6 s. The outcome of the reaction can be tuned by simply using either a basic or an acidic quench. Very good to excellent isolated yields, up to 97%, have been obtained for most cases (30 examples).
• Solvent and in situ catalyst preparation impacts upon Noyori reductions of aryl-chloromethyl ketones: application to syntheses of chiral 2-amino-1-aryl-ethanols
  作者：Steven P. Tanis、Bruce R. Evans、James A. Nieman、Timothy T. Parker、Wendy D. Taylor、Steven E. Heasley、Paul M. Herrinton、William R. Perrault、Richard A. Hohler、Lester A. Dolak、Matthew R. Hester、Eric P. Seest

  DOI：10.1016/j.tetasy.2006.07.017

  日期：2006.8

  As part of medicinal chemistry efforts we found it necessary to develop general syntheses of highly enantiomerically enriched 1-aryl-2-chloroethanols and 1-aryl-2-methylaminoethanols. A survey of literature methods suggested that a truly general approach had not yet been reported, encouraging us to undertake the development of such a methodology. This study describes the design, development, and reduction to practice of a general synthesis of chiral 1-aryl-2-chloroethanols and the transformation of these entities to highly enantiomerically enriched 1-aryl-2-methylaminoethanols. Of particular importance were observations of the impact of solvent and the method of catalyst preparation on the yield and enantiomerical excess of chlorohydrins prepared via Noyori transfer hydrogenations of aryl-chloromethyl ketones. (c) 2006 Elsevier Ltd. All rights reserved.
• Chemoenzymatic synthesis of duloxetine and its enantiomer: lipase-catalyzed resolution of 3-hydroxy-3-(2-thienyl) propanenitrile
  作者：Ahmed Kamal、G.B.Ramesh Khanna、R Ramu、T Krishnaji

  DOI：10.1016/s0040-4039(03)00945-6

  日期：2003.6

  An efficient and facile chemoenzymatic synthesis of duloxetine by lipase mediated resolution of 3-hydroxy-3-(2-thienyl)propanenitrile has been achieved. This process also describes an en antioconvergent synthesis of duloxetine via a Mitsunobu reaction. (C) 2003 Elsevier Science Ltd. All rights reserved.