2,2-二氟-1-(4-甲氧基苯基)-1-丙酮 | 144464-70-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2,2-二氟-1-(4-甲氧基苯基)-1-丙酮
• 英文名称: α,α-difluoro-p-methoxypropiophenone
• 英文别名: 2,2-difluoro-1-(4-methoxyphenyl)propan-1-one；1-Propanone, 2,2-difluoro-1-(4-methoxyphenyl)-
• CAS: 144464-70-0
• 化学式: C₁₀H₁₀F₂O₂
• 分子量: 200.185
• InChiKey: HQYOCZCFHYGCKD-UHFFFAOYSA-N

物化性质

• 沸点：
  276.2±30.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,2-二氟-1-(4-甲氧基苯基)-1-丙酮 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 66.0h， 生成 ethyl 4,4-difluoro-3-(p-methoxyphenyl)pentanoate
  参考文献：
  名称：

  Synthesis of DL-threo-3-(1-fluoro-1-methylethyl)- and DL-threo-3-(1,1-difluoroethyl)malic acids. Mechanistic studies of 3-isopropylmalate dehydrogenase

  摘要：

  For both mechanistic studies and the development of novel inhibitors of 3-isopropylmalate dehydrogenase enzyme (IPMDH), which is involved in the rate-determining step in the biosynthetic pathway of the essential amino acid L-leucine, (2R*,3S*)-3-(1-fluoro-1-methylethyl)- and (2R*,3S*)-3-(1,1-difluoroethyl)malic acids (F-IPM and F-2-EM) were designed based on the concept of mechanism-based inhibition, and the reaction kinetics with these fluorinated substrates were analysed, The reaction of F-IPM with IPMDH was studied by NMR spectroscopy and product isolation. F-IPM underwent, after the normal enzyme reaction, the expected additional elimination reaction to afford an alpha,beta-unsaturated carbonyl product, which turned out not to participate in any covalent-bond-forming reaction. The conformation of the reaction intermediate during the IPMDH reaction and the functional-group arrangement in the active site of IPMDH are discussed.

  DOI：

  10.1039/p19950001905
• 作为产物：
  描述：

  Anisoyl propionic acid 在 Selectfluor 作用下， 以 硝基甲烷 为溶剂， 反应 18.0h， 以20%的产率得到2,2-二氟-1-(4-甲氧基苯基)-1-丙酮
  参考文献：
  名称：

  通过β-酮酸的直接脱羧二氟化实际获得二氟甲基酮

  摘要：

  已经描述了一种简便的合成方法，可从β-酮酸合成一系列二氟甲基酮。这种转化是通过在没有任何催化剂的情况下，通过β-酮酸的直接脱羧二氟化来实现的。此外，所得的二氟甲基酮可以容易地转化为用于药物和材料的相应的二氟甲基化的结构单元。

  DOI：

  10.1002/adsc.201601315

文献信息

• Difluorohomologation of Ketones
  作者：Mikhail D. Kosobokov、Vitalij V. Levin、Marina I. Struchkova、Alexander D. Dilman

  DOI：10.1021/acs.orglett.5b00097

  日期：2015.2.6

  CF2 fragment is described. The reaction involves silylation, room-temperature difluorocyclopropanation of silyl enol ethers, and selective ring opening of cyclopropanes under acidic conditions. The whole three-step sequence is conveniently performed in a one-pot mode.

  描述了一种使CF 2片段与酮同源的方法。该反应包括甲硅烷基化，甲硅烷基烯醇醚的室温二氟环丙烷化和在酸性条件下环丙烷的选择性开环。整个三步顺序可在一锅模式下方便地执行。
• Bench‐Stable Electrophilic Fluorinating Reagents for Highly Selective Mono‐ and Difluorination of Silyl Enol Ethers
  作者：Akiya Adachi、Kohsuke Aikawa、Yuichiro Ishibashi、Kyoko Nozaki、Takashi Okazoe

  DOI：10.1002/chem.202101499

  日期：2021.8.16

  the synthesis of fluorinated compounds have been intensively studied, recently. Development of practical fluorinating reagents is indispensable for this purpose. Herein, bench-stable electrophilic fluorinating reagents were synthesized as N-fluorobenzenesulfonimide (NFSI) substitutes. Reagents obtained by replacing one of the NFSI sulfonyl groups with an acyl group led to the highly selective monofluorination

  最近，人们对合成含氟化合物的有效方法进行了深入研究。为此，开发实用的氟化试剂是必不可少的。在此，工作台稳定的亲电子氟化试剂被合成为N-氟苯磺酰亚胺(NFSI) 替代品。通过用酰基取代 NFSI 磺酰基之一获得的试剂导致甲硅烷基烯醇醚的高度选择性单氟化，同时抑制了不希望的过度反应，即二氟化。另一方面，在 NFSI 苯磺酰基上带有吸电子取代基的试剂在无碱条件下有效地促进了甲硅烷基烯醇醚的二氟化。因此，单氟化和二氟化靶材料均由同一基材制备。
• Remarkable reversal of stereoselectivity in Wittig-type olefinations of α-fluorinated alkyl aryl ketones
  作者：Tadashi Eguchi、Tetsuya Aoyama、Katsumi Kakinuma

  DOI：10.1016/s0040-4039(00)61141-3

  日期：1992.9

  reversal of stereoselectivity in the Wittig-type olefinations of α-fluorinated alkyl aryl ketones were described. Stabilized Wittig and Horner-Emmons reagents with these ketones selectively afforded the olefinic products in the stereochemically oppposite fashion to the non-flourinated ketone cases. The Still's reagent further reversed the stereochemical outcome with the fluorinated ketones.

  描述了在α-氟化烷基芳基酮的维蒂希型烯化反应中显着的反应性和立体选择性的逆转。具有这些酮的稳定化的Wittig和Horner-Emmons试剂选择性地提供了与非氟化酮盒立体化学相反的烯烃产物。斯蒂尔试剂与氟化酮进一步逆转了立体化学结果。
• Practical Access to Difluoromethyl Ketones via Straightforward Decarboxylative Difluorination of β-Ketoacids
  作者：Yin-Long Li、Jian Li、Jun Deng

  DOI：10.1002/adsc.201601315

  日期：2017.4.17

  A facile synthetic approach to a series of difluoromethyl ketones from β‐ketoacids has been described. This transformation is achieved through the straightforward decarboxylative difluorination of β‐ketoacids in the absence of any catalyst. Furthermore, the resulted difluoromethyl ketones can be easily converted into corresponding difluoromethylated building blocks for pharmaceuticals and materials

  已经描述了一种简便的合成方法，可从β-酮酸合成一系列二氟甲基酮。这种转化是通过在没有任何催化剂的情况下，通过β-酮酸的直接脱羧二氟化来实现的。此外，所得的二氟甲基酮可以容易地转化为用于药物和材料的相应的二氟甲基化的结构单元。
• Synthesis of DL-threo-3-(1-fluoro-1-methylethyl)- and DL-threo-3-(1,1-difluoroethyl)malic acids. Mechanistic studies of 3-isopropylmalate dehydrogenase
  作者：Tetsuya Aoyama、Tadashi Eguchi、Tairo Oshima、Katsumi Kakinuma

  DOI：10.1039/p19950001905

  日期：——

  For both mechanistic studies and the development of novel inhibitors of 3-isopropylmalate dehydrogenase enzyme (IPMDH), which is involved in the rate-determining step in the biosynthetic pathway of the essential amino acid L-leucine, (2R*,3S*)-3-(1-fluoro-1-methylethyl)- and (2R*,3S*)-3-(1,1-difluoroethyl)malic acids (F-IPM and F-2-EM) were designed based on the concept of mechanism-based inhibition, and the reaction kinetics with these fluorinated substrates were analysed, The reaction of F-IPM with IPMDH was studied by NMR spectroscopy and product isolation. F-IPM underwent, after the normal enzyme reaction, the expected additional elimination reaction to afford an alpha,beta-unsaturated carbonyl product, which turned out not to participate in any covalent-bond-forming reaction. The conformation of the reaction intermediate during the IPMDH reaction and the functional-group arrangement in the active site of IPMDH are discussed.