氯(二氟)乙酸烯丙酯 | 118337-48-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 氯(二氟)乙酸烯丙酯
• 英文名称: allyl chlorodifluoroacetate
• 英文别名: prop-2-enyl 2-chloro-2,2-difluoroacetate
• CAS: 118337-48-7
• 化学式: C₅H₅ClF₂O₂
• mdl: MFCD09033650
• 分子量: 170.543
• InChiKey: RVOSMQFOBYVXQI-UHFFFAOYSA-N

物化性质

• 沸点：
  98 °C
• 密度：
  1.292±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2915900090

反应信息

• 作为反应物：
  描述：

  氯(二氟)乙酸烯丙酯 在 sodium hydroxide 、 三甲基氯硅烷 、 碘 、 锌 作用下， 以 乙腈 为溶剂， 以59.4 g (74%)的产率得到2,2-二氟-4-戊烯酸
  参考文献：
  名称：

  Process for the preparation of 2,2-difluoropent-4-enoic acids and acid

  摘要：

  联丙基溴或氯二氟乙酸酯与单氯硅烷在锌的存在下加热反应，生成α,α-二氟-γ,δ-戊烯酸的硅酯。通过水解可以得到自由酸，从而可以通过传统方法制备酸衍生物。戊烯酸和戊烯酸衍生物适用于制备聚合物和共聚物，从中可以获得具有催化性能的金属有机聚合物和共聚物。

  公开号：

  US04892962A1
• 作为产物：
  描述：

  氯二氟乙酸酐 、 烯丙醇 在 三乙胺 作用下， 以 乙醚 为溶剂， 反应 2.0h， 以90%的产率得到氯(二氟)乙酸烯丙酯
  参考文献：
  名称：

  Fluorinated Analogs as Mechanistic Probes in Valproic Acid Hepatotoxicity: Hepatic Microvesicular Steatosis and Glutathione Status

  摘要：

  It is postulated that the hepatotoxicity of valproic acid (VPA) results from the mitochondrial beta-oxidation of its cytochrome P450 metabolite, 2-propyl-4-pentenoic acid (4-ene VPA), to 2-propyl-(E)-2,4-pentadienoic acid ((E)-2,4-diene VPA) which, in the CoA thioester form, either depletes GSH or produces a putative inhibitor of beta-oxidation enzymes. In order to test this hypothesis, 2-fluoro-2-propyl-4-pentenoic acid (alpha-fluoro-4-ene VPA) which was expected to be inert to beta-oxidative metabolism was synthesized and its effect on rat liver studied in comparison with that of 4-ene VPA. Similarly, the known hepatotoxicant 4-pentenoic acid (4-PA) and 2,2-difluoro-4-pentenoic acid (F-2-4-PA) were compared. Male Sprague-Dawley rats (150-180 g, 4 rats per group) were dosed ip with 4-ene VPA (0.7 mmol/kg per day), 4-PA (1.0 mmol/kg per day), or equivalent amounts of their alpha-fluorinated analogues for 5 days. Both 4-ene VPA and 4-PA induced severe hepatic microvesicular steatosis (> 85% affected hepatocytes), and 4-ene VPA produced mitochondrial alterations. By contrast, alpha-fluoro-4-ene VPA and F-2-4-PA were not observed to cause morphological changes in the liver. The major metabolite of 4-ene VPA in the rat urine and serum was the beta-oxidation product (E)-2,4-diene VPA. The N-acetylcysteine (NAC) conjugate of (E)-2,4-diene VPA was also found in the urine. Neither (E)-2,4-diene VPA nor the NAC conjugate could be detected in the rats administered alpha-fluoro-4-ene VPA. In a second set of rats (3 rats per group), total liver GSH levels were determined to be depleted to 56% and 72% of control following doses of 4-ene VPA (1.4 mmol/kg); and equivalent alpha-fluoro-4-ene VPA, respectively. Mitochondrial GSH remained unchanged in the (alpha-fluoro-4-ene VPA treated group but was reduced to 68% of control in the rats administered 4-ene VPA. These results strongly support the theory that hepatotoxicity of 4-ene VPA, and possibly VPA itself, is mediated largely through beta-oxidation of 4-ene VPA to reactive intermediates that are capable of depleting mitochondrial GSH.

  DOI：

  10.1021/tx00047a006

文献信息

• [EN] PROCESS FOR THE PREPARATION OF ROFLUMILAST<br/>[FR] PROCEDE DE PREPARATION DE ROFLUMILAST
  申请人：RANBAXY LAB LTD

  公开号：WO2005026095A1

  公开（公告）日：2005-03-24

  The present invention relates to a process for the preparation of 3-cyclopropylmethoxy-4-difluromethoxy benzoic acid of structural Formula I, and to the use of this compound as an intermediate for the preparation of roflumilast.

  本发明涉及一种制备结构式I中的3-环丙基甲氧基-4-二氟甲氧基苯甲酸的方法，以及将该化合物用作制备洛氟米拉斯特的中间体的用途。
• Fluorine-containing organozinc reagents. V.
  作者：Hans Greuter、Robert W. Lang、Andres J. Romann

  DOI：10.1016/0040-4039(88)85143-8

  日期：1988.1

  Silicon induced Reformatskii-Claisen reaction of allyl chlorodifluoroacetate () affords 2,2-difluoro-4-pentenoic acid () in good yields. Starting from inexpensive chloro-difluoroacetic acid, a variety of useful fluorine-containing synthetic building blocks can be obtained under the same reaction conditions.

  硅诱导的氯二氟乙酸烯丙酯的Reformatskii-Claisen反应（）以高收率提供2,2-二氟-4-戊烯酸（）。从廉价的氯二氟乙酸开始，可以在相同的反应条件下获得各种有用的含氟合成构件。
• Method for producing difluoro-acetyl-acetic acid alkylesters
  申请人：Gallenkamp Bernd

  公开号：US20060149091A1

  公开（公告）日：2006-07-06

  The present invention relates to a three-step method for the preparation of alkyl esters of 4,4-difluoroacetoacetic acid in which in the first step alkyl esters of 4-chloro-4,4-difluoroacetic acid are reacted with trialkylphosphites of formula (III) P(OR 1 ) 3 (III) in which R 1 stands for C 1 -C 4 -alkyl, whereby the residues R 1 can in each case be the same or different, to form alkyl phosphonates of formula (IV) which in the next step are reacted with an amine of formula (V), in which R 2 and R 3 independent of each other stand for hydrogen or C 1 -C 4 -alkyl or together form —CH 2 —CH 2 —O—CH 2 —CH 2 —, to form enamines of formula (VI), in which R 2 and R 3 have the meanings described above, which in the third step are hydrolyzed in the presence of an acid.

  本发明涉及一种制备4,4-二氟乙酰乙酸烷基酯的三步方法，其中在第一步中，4-氯-4,4-二氟乙酸烷基酯与化学式（III）P（OR1）3（III）的三烷基膦酸酯反应，其中R1代表C1-C4烷基，残基R1可以分别相同或不同，形成化学式（IV）的烷基膦酸酯，然后在下一步中与化学式（V）的胺反应，其中R2和R3独立地代表氢或C1-C4烷基，或者一起形成-CH2- -O- - -，形成化学式（VI）的烯胺，其中R2和R3具有上述所述的含义，在第三步中在酸存在下水解。
• Gmelin Handbuch der Anorganischen Chemie, Gmelin Handbook: Ni: Org.Verb.2, 2.3.1, page 271 - 289
  作者：

  DOI：——

  日期：——
• Novel synthesis of 2,2,2-trifluoroethyl compounds from homoallylic alcohols: a copper(<scp>I</scp>) iodide-initiated trifluoromethyl–dehydroxylation process
  作者：Jian-Xing Duan、Qing-Yun Chen

  DOI：10.1039/p19940000725

  日期：——

  Benzyl, prop-2-ynyl and allyl chlorodifluoroacetates 3a, bromodifluoroacetates 3b or fluorosulfonyl-difluoroacetates 3c, when decomposed in the presence of 1 equivalent of copper(I) iodide at an appropriate temperature in dimethylformamide, gave the corresponding trifluoromethyl derivatives in good to excellent yields. The products can also be obtained directly by ester exchange of XCF2CO2Et (X = FSO2, Cl, Br) 6 and the corresponding alcohols in the presence of KF and Cul. A trifluoromethylation-dehydroxylation mechanism, initiated by Cul, is proposed.