4-(2-fluoro-1-hydroxyethyl)benzonitrile | 1073056-22-0

• 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: 4-(2-fluoro-1-hydroxyethyl)benzonitrile
• CAS: 1073056-22-0
• 化学式: C₉H₈FNO
• 分子量: 165.167
• InChiKey: YWDWJWQHEJOOSI-UHFFFAOYSA-N

物化性质

• 沸点：
  325.3±37.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12
• 可旋转键数：
  2
• 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：
  3

反应信息

• 作为反应物：
  描述：

  邻苯二甲酸亚胺 、 4-(2-fluoro-1-hydroxyethyl)benzonitrile 在 四氢呋喃 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 对氰基苯乙酮 、 (S)-4-(1-(1,3-dioxoisoindolin-2-yl)-2-fluoroethyl)benzonitrile 、 (R)-4-(1-(1,3-dioxoisoindolin-2-yl)-2-fluoroethyl)benzonitrile
  参考文献：
  名称：

  对映体富集的1-芳基-2-氟乙胺。高效脂肪酶催化的拆分和对Mitsunobu转化方案的限制

  摘要：

  八个1-芳基-2-氟乙胺的两种对映体均以1-芳基-2-氟乙酮为原料合成。使用南极假丝酵母的脂肪酶B和甲氧基乙酸乙酯作为酰基供体对胺进行动力学拆分，得到96.99％ee的（R）-胺和> 99.5％ee的（S）-甲氧基乙酰胺。关于反应温度，酰基给体浓度，水活度和底物结构的变化，分离度很强。其他九种脂肪酶制剂未能催化该反应或对映选择性低。其次，在合成（（S）时，采用以苯二甲酰亚胺为亲核试剂的对映体富集的1-芳基-2-氟乙醇为原料的Mitsunobu转化方案。）-1-芳基-2-氟乙胺。转化效率和产率均取决于芳族取代基。对于六种底物，观察到立体化学的完全反转。但是，当芳族环上存在供电子性取代基时，外消旋化和低收率是结果。当用氰基或硝基取代时，会发生意想不到的氟消除，从而限制了这些转化的收率。使用圆二色性确定1-芳基-2-氟乙胺的绝对构型。

  DOI：

  10.1016/j.tet.2010.06.081
• 作为产物：
  描述：

  4-(2-fluoroacetyl)benzonitrile 在 sodium tetrahydroborate 作用下， 生成 4-(2-fluoro-1-hydroxyethyl)benzonitrile
  参考文献：
  名称：

  Asymmetric reduction using (R)-MeCBS and determination of absolute configuration of para-substituted 2-fluoroarylethanols

  摘要：

  The asymmetric reduction of eight alpha-fluoroacetophenones has been investigated using (R)-MeCBS as a catalyst in various media. Based on a solvent screen, 1,2-dimethoxyethane, diethyl ether and dichloromethane were used in reductions of the alpha-fluoroacetophenones. The enantiomeric excess of the products depended oil the solvent and the electronic character of the aromatic substituents. Higher enantioselectivity and less solvent dependency were observed in the reduction of substrates bearing electron donating substituents, whereas the opposite was the case for reduction of the substrates with electron withdrawing substituents. The (R)-2-fluoro-1-arylethanols were obtained with enantiomeric excesses in the range of 91-99% using 1,2-dimethoxyethane as a solvent. Six of the alcohols produced are new chemical entities. The absolute configurations of the (R)-2-fluoro-1-arylethanols were determined by circular dichroism using the exciton chirality method of tile (S)-benzoate esters of the alcohols. The (S)-benzoate esters were obtained by lipase-catalysed resolution using Novozym 435. (C) 2008 Elsevier Ltd. All Fights reserved.

  DOI：

  10.1016/j.tetasy.2008.07.019

文献信息

• Exploiting a “Beast” in Carbenoid Chemistry: Development of a Straightforward Direct Nucleophilic Fluoromethylation Strategy
  作者：Giovanna Parisi、Marco Colella、Serena Monticelli、Giuseppe Romanazzi、Wolfgang Holzer、Thierry Langer、Leonardo Degennaro、Vittorio Pace、Renzo Luisi

  DOI：10.1021/jacs.7b07891

  日期：2017.10.4

  The first direct and straightforward nucleophilic fluoromethylation of organic compounds is reported. The tactic employs a "fleeting" lithium fluorocarbenoid (LiCH2F) generated from commercially available fluoroiodomethane. Precise reaction conditions were developed for the generation and synthetic exploitation of such a labile species. The versatility of the strategy is showcased in ca. 50 examples involving a plethora of electrophiles. Highly valuable chemicals such as fluoroalcohols, fluoroamines, and fluoromethylated oxygenated heterocycles could: be prepared in very good yields through a single synthetic operation. The scalability of the reaction and its application to complex molecular architectures (e.g., steroids) are documented.