diethyl 2-(difluoromethyl)-2-phenylmalonate | 791-25-3

• 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: diethyl 2-(difluoromethyl)-2-phenylmalonate
• 英文别名: Diethyl 2-(difluoromethyl)-2-phenylpropanedioate
• CAS: 791-25-3
• 化学式: C₁₄H₁₆F₂O₄
• 分子量: 286.275
• InChiKey: BUXRKUZOSZXAMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  氟里昂-22 、 苯基丙二酸二乙酯 在 苄基三乙基氯化铵 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以64%的产率得到diethyl 2-(difluoromethyl)-2-phenylmalonate
  参考文献：
  名称：

  Difluoromethylation of some C–H acids with chlorodifluoromethane under conditions of phase transfer catalysis (PTC)

  摘要：

  Selected C-H acids react with difluorocarbene generated from chlorodifluoromethane with concentrated aqueous solution of sodium hydroxide, and a catalyst, benzyltriethylammonium chloride (TEBAC) in benzene or THF affording C-difluoromethyl substituted derivatives. This process is restricted to C-H acids of pK(a) congruent to 16.3-19.1. The observed facts are rationalized. (C) 2009 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jfluchem.2009.02.008

文献信息

• Air- and Light-Stable <i>S</i>-(Difluoromethyl)sulfonium Salts: <i>C</i>-Selective Electrophilic Difluoromethylation of β-Ketoesters and Malonates
  作者：Sheng-Le Lu、Xin Li、Wen-Bing Qin、Jian-Jian Liu、Yi-Yong Huang、Henry N. C. Wong、Guo-Kai Liu

  DOI：10.1021/acs.orglett.8b03067

  日期：2018.11.2

  Air- and light-stable electrophilic difluoromethylating reagents, S-(difluoromethyl)-S-phenyl-S-(2,4,6-trialkoxyphenyl) sulfonium salts were successfully developed, and the introduction of intramolecular hydrogen bonds plays a crucial role for the stabilities and reactivities of these reagents. C-selective difluoromethylation of a broad range of β-ketoesters and malonates proceeded smoothly under mild

  空气和光稳定的亲电子二氟甲基化试剂，S-（二氟甲基）-S-苯基-S-（2,4,6-三烷氧基苯基）salts盐已成功开发，并且分子内氢键的引入对于该化合物起着至关重要的作用。这些试剂的稳定性和反应性。在温和的反应条件下，各种β-酮酸酯和丙二酸酯的C选择性二氟甲基化反应平稳进行，从而以良好的C / O区域选择性提供了良好至优异的收率。
• Carbon-Selective Difluoromethylation of Soft Carbon Nucleophiles with Difluoromethylated Sulfonium Ylide
  作者：Jiansheng Zhu、Hanliang Zheng、Xiao-Song Xue、Yisa Xiao、Yafei Liu、Qilong Shen

  DOI：10.1002/cjoc.201800383

  日期：2018.11

  highly carbon‐selective difluoromethylation of soft carbon nucleophiles including β‐ketoesters, malonates, oxindoles, benzofuranones and ketene silyl acetals with a difluoromethylated sulfonium ylide under mild conditions was described. Mechanistic studies suggest that these difluoromethylating reactions proceed via a difluorocarbene pathway.

  描述了在温和条件下用二氟甲基化叶立德对软碳亲核试剂（包括β-酮酸酯，丙二酸酯，羟吲哚，苯并呋喃酮和乙烯酮甲硅烷基乙缩醛）进行高碳选择性二氟甲基化。机理研究表明，这些二氟甲基化反应是通过二氟卡宾途径进行的。
• A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF ₂ Br
  作者：Qiqiang Xie、Ziyue Zhu、Lingchun Li、Chuanfa Ni、Jinbo Hu

  DOI：10.1002/anie.201900763

  日期：2019.5.6

  efficient method for the selective C‐difluoromethylation of carbon acids with the reagent TMSCF2Br has been developed. A variety of structurally diverse sp3‐ and sp‐hybridized carbon nucleophiles, including esters, amides, fluorenes, terminal alkynes, β‐ketoesters, malonates, and other activated C−H nucleophiles, could be efficiently and selectively transformed into the corresponding C‐difluoromethylated

  已经开发出一种有效的方法，可通过试剂TMSCF 2 Br选择性地对碳进行C-二氟甲基化。各种结构多样的sp 3和sp杂化的碳亲核试剂，包括酯，酰胺，芴，末端炔烃，β-酮酸酯，丙二酸酯和其他活化的C-H亲核试剂，都可以有效地并选择性地转化为相应的C-亲核试剂。在温和条件下的二氟甲基化产物。该方案对于药物相关分子的晚期二氟甲基化也很有效，并且可以很容易地扩大规模。此外，可以使用TMSCF 2 Br对二氟卡宾具有一个以上反应位点的环境底物进行正交二氟甲基化。
• Utilization of fluoroform for difluoromethylation in continuous flow: a concise synthesis of α-difluoromethyl-amino acids
  作者：Manuel Köckinger、Tanja Ciaglia、Michael Bersier、Paul Hanselmann、Bernhard Gutmann、C. Oliver Kappe

  DOI：10.1039/c7gc02913f

  日期：——

  be considered as an ideal reagent for difluoromethylation reactions. However, due to the low reactivity of fluoroform, only very few applications have been reported so far. Herein we report a continuous flow difluoromethylation protocol on sp3 carbons employing fluoroform as a reagent. The protocol is applicable for the direct Cα-difluoromethylation of protected α-amino acids, and enables a highly atom

  氟仿（CHF 3）被认为是二氟甲基化反应的理想试剂。然而，由于氟仿的低反应性，迄今为止仅报道了很少的应用。在本文中，我们报告了使用氟仿作为试剂在sp 3碳上连续流动的二氟甲基化方案。该协议是适用于直接Ç α保护的α氨基酸的-difluoromethylation，并且使活性药物成分依氟鸟氨酸的高度原子有效合成。
• Use of fluoroform as a source of difluorocarbene in the synthesis of N -CF 2 H heterocycles and difluoromethoxypyridines
  作者：Charles S. Thomoson、Linhua Wang、William R. Dolbier

  DOI：10.1016/j.jfluchem.2014.08.015

  日期：2014.12

  Fluoroform is used as a source of difluorocarbene to convert various N-, O-, and C-nucleophiles to their difluoromethylated derivatives. Imidazole, benzimidazole, benztriazole, hydroxypyridines, and their derivatives underwent reaction at moderate temperatures and atmospheric pressure, using potassium hydroxide as base in a two-phase (water/acetonitrile) process to provide moderate to good yields of the respective products. Nitrophenols required addition of a co-solvent (methanol) to obtain good yields of products. (C) 2014 Elsevier B.V. All rights reserved.