4,4,4-trifluoro-3-hydroxy-butyronitrile | 57165-85-2

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 卤代醇
• 英文名称: 4,4,4-trifluoro-3-hydroxy-butyronitrile
• 英文别名: 3-hydroxy-4,4,4-trifluorobutyronitrile；4,4,4-Trifluoro-3-hydroxybutanenitrile
• CAS: 57165-85-2
• 化学式: C₄H₄F₃NO
• mdl: MFCD11099999
• 分子量: 139.077
• InChiKey: NCKPCYRKCHNXIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,4,4-trifluoro-3-hydroxy-butyronitrile 在 sodium tetrahydroborate 、 nickel dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-氨基-3-羟基-4,4,4-三氟丁烷
  参考文献：
  名称：

  One-pot Sequence for the Decarboxylation of α-Amino Acids

  摘要：

  在pH 5的水溶液中或酒精-水氨氯混合液中，使用N-溴代琥珀酰亚胺处理α-氨基酸，随后加入氯化镍(II)和硼氢化钠，通过中间体腈实现了整体脱羧反应，从而以良好的产率获得了相应的胺。

  DOI：

  10.1055/s-2003-37512
• 作为产物：
  描述：

  2-(3,3,3-trifluoro-2-hydroxypropyl)glycine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 phosphate buffer 、 N,N-二甲基甲酰胺 为溶剂， 生成 4,4,4-trifluoro-3-hydroxy-butyronitrile
  参考文献：
  名称：

  One-pot Sequence for the Decarboxylation of α-Amino Acids

  摘要：

  在pH 5的水溶液中或酒精-水氨氯混合液中，使用N-溴代琥珀酰亚胺处理α-氨基酸，随后加入氯化镍(II)和硼氢化钠，通过中间体腈实现了整体脱羧反应，从而以良好的产率获得了相应的胺。

  DOI：

  10.1055/s-2003-37512

文献信息

• Phosphinic Acid Analogs of GABA. 1. New Potent and Selective GABAB Agonists
  作者：Wolfgang Froestl、Stuart J. Mickel、Roger G. Hall、Georg von Sprecher、Dietrich Strub、Peter A. Baumann、Felix Brugger、Conrad Gentsch、Joachim Jaekel

  DOI：10.1021/jm00017a015

  日期：1995.8

  replacing the carboxylic acid group of GABA or baclofen derivatives with either the phosphinic acid or the methylphosphinic acid residue. Surprisingly, ethyl- and higher alkylphosphinic acid derivatives of GABA yielded novel GABAB antagonists, which are described in part 2 of this series. Structure-activity relationships of the novel GABAB agonists are discussed with respect to their affinities to GABAB

  抗痉挛剂和肌肉松弛剂巴氯芬1是对双小分子不敏感的GABA B受体的有效选择性激动剂。多年来，获得出色的GABA B激动剂的努力一直没有成功。我们描述了两个新系列的GABA B激动剂的合成和生物学特性，在体外和体内，最好的化合物比巴氯芬更有效。它们是通过用次膦酸或甲基次膦酸残基取代GABA或巴氯芬衍生物的羧酸基团而获得的。出人意料的是，GABA的乙基和高级烷基次膦酸衍生物产生了新型GABAB拮抗剂，在本系列的第2部分中对此进行了描述。
• Facile and Selective Alkylation of 3,3,3-Trifluoropropene Oxide (TFPO) with Organoaluminum Reagents via Pentacoordinate Trialkylaluminum Complexes
  作者：Takashi Ooi、Mayumi Furuya、Keiji Maruoka

  DOI：10.1246/cl.1998.817

  日期：1998.8

  A new organoaluminum-promoted selective alkylation of 3,3,3-trifluoropropene oxide (TFPO) with several nucleophiles has been developed which involves the chelation-activated addition to fluoro epoxides via pentacoordinate trialkylaluminum complexes.

  已经开发了一种新的有机铝促进的 3,3,3-三氟环氧丙烷 (TFPO) 与几种亲核试剂的选择性烷基化，其中涉及通过五配位三烷基铝配合物螯合活化加成到氟环氧化物中。
• Oxa-Michael Addition to α,β-Unsaturated Nitriles: An Expedient Route to γ-Amino Alcohols and Derivatives
  作者：Beibei Guo、Douwe S. Zijlstra、Johannes G. de Vries、Edwin Otten

  DOI：10.1002/cctc.201800509

  日期：2018.7.9

  Water addition to α,β‐unsaturated nitriles would give facile access to the β‐hydroxy‐nitriles, which in turn can be hydrogenated to the γ‐amino alcohols. We have previously shown that alcohols readily add in 1,4‐fashion to these substrates using Milstein's Ru(PNN) pincer complex as catalyst. However, attempted water addition to α,β‐unsaturated nitriles gave the 3‐hydroxynitriles in mediocre yields

  α,β-不饱和腈中加水可以很容易地得到β-羟基腈，而β-羟基腈又可以氢化成γ-氨基醇。我们之前已经证明，使用 Milstein 的 Ru(PNN) 钳配合物作为催化剂，醇很容易以 1,4-方式添加到这些底物中。然而，尝试将水添加到 α,β-不饱和腈中，得到的 3-羟基腈收率平平。另一方面，苯甲醇的加成反应对各种β-取代不饱和腈的产率都很高。随后用 TMSCl/FeCl 3处理苯甲醇加成产物，形成 3-羟基烷基腈。由 oxa-Michael 加成得到的 3-苄氧基-烷基腈也可以在酸存在下直接氢化，以优异的收率得到 HCl 盐形式的氨基醇。在中性条件下氢化得到仲胺和叔胺的混合物。在碱和 Boc 酸酐存在下氢化，得到正交双保护的氨基醇，其中苄基醚随后可裂解生成 Boc 保护的氨基醇。因此，从苯甲醇与 α,β-不饱和腈的 oxa-Michael 加成开始，可以得到各种O和N官能团之间具有 1,3-关系的分子支架。
• Synthesis and antitumor activity of 6-trifluoromethylcyclophosphamide and related compounds
  作者：Peter B. Farmer、Peter J. Cox

  DOI：10.1021/jm00245a012

  日期：1975.11

  In an attempt to increase the combined toxicity of the metabolic end-products [acrolein (4) and phosphoramide mustard (3)] from cyclophosphamide (1), the analog 2-[bis(2-chloroethyl)amino]tetrahydro-6-trifluoromethyl-2H-1,3,2-oxazaphosphorine 2-oxide (2, 6-trifluoromethylcyclophosphamide) was synthesized and its metabolism and antitumor activity studied. Following metabolism of 2 by rat liver microsomes the predicted formation of 4,4,4-trifluorocrotonaldehyde (5) was confirmed by isolation and identification, by mass spectrometry, of its dinitrophenylhydrazone. The therapeutic indices (LD50-/ID90) for 2 against the ADJ/PC6 mouse tumor and the Walker 256 tumor in the rat were 28.6 and 7.7, respectively, and were lower than the corresponding values for 1 (91.8 and 33.2, respectively) although the toxicities toward Walker cells in a bioassay system of 1 and 2 following microsomal metabolism were similar. In order to study the toxicities of 4 and 5 released under drug metabolizing conditions independently of the production of a toxic mustard the analogs 18 [2-(diethylamino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide] and 6 [2-(diethylamino)tetrahydro-6-trifluoromethyl-2H-1,3,2-oxazaphosphorine 2-oxide] were also synthesized. The release of 5 from 6 following metabolism was confirmed and shown by use of the bioassay system to be an event of similar toxicity to release of 4 from 18; in vivo, however, 6 (LD50 330 mg/kg) was more toxic to mice than 18 (LD50 greater than 500 mg/kg).
• One-pot Sequence for the Decarboxylation of α-Amino Acids
  作者：Bernard T. Golding、Gilles Laval

  DOI：10.1055/s-2003-37512

  日期：——

  Treatment of an α-amino acid with N-bromosuccinimide in water at pH 5 or in an alcoholic-aqueous ammonium chloride mixture, followed by addition of nickel(II) chloride and sodium borohydride, effected an overall decarboxylation via an intermediate nitrile to afford the corresponding amine in good yield.

  在pH 5的水溶液中或酒精-水氨氯混合液中，使用N-溴代琥珀酰亚胺处理α-氨基酸，随后加入氯化镍(II)和硼氢化钠，通过中间体腈实现了整体脱羧反应，从而以良好的产率获得了相应的胺。

表征谱图