2,2-difluorooctanoic acid | 142977-59-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2,2-difluorooctanoic acid
• CAS: 142977-59-1
• 化学式: C₈H₁₄F₂O₂
• 分子量: 180.195
• InChiKey: MLOWNTBEVYDWSG-UHFFFAOYSA-N

物化性质

• 沸点：
  234.7±25.0 °C(Predicted)
• 密度：
  1.084±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,2-difluorooctanoic acid 在 phosphorus pentoxide 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 96.0h， 生成 2,2-difluoro-N,N-dioctyloctanamide
  参考文献：
  名称：

  Amines That Transport Protons across Bilayer Membranes:  Synthesis, Lysosomal Neutralization, and Two-Phase pK_a Values by NMR

  摘要：

  It is desirable to be able to control the pH of lysosomes. A collection of lipophilic, nitrogenous bases, designed to act as membrane-active, catalytic proton transfer agents, were prepared and their effective pK(a)s measured in a vigorously stirred, two-phase system. One phase was a phosphate buffer whose pH was varied over the range ca, 1-11. The other was an immiscible, deuterated organic solvent in which the compounds preferentially resided even when protonated. When chemical shift changes versus the pH of the buffer were plotted, clear pK(a) curves were generated that are relevant to transmembrane proton transfer behavior. The two-phase pK(a)s increased with increasing counterion lipophilicity and with increasing organic solvent polarity, The compounds were also tested for their ability to neutralize the acidity of lysosomes, a model for other acidic vesicles involved in drug sorting. The most successful of these, imidazole 6a, has > 100 times the neutralizing power of ammonia, a standard lysosomotropic amine, causing a 1.7 unit rise in lysosomal pH of RAW cells at 0.1 mM, compared to a 0.2 and 1.4 unit rise for ammonium chloride at 0.1 and 10 mM, respectively.

  DOI：

  10.1021/jo960367f
• 作为产物：
  描述：

  庚酸甲酯 在 盐酸 、 氢氧化钾 、 二乙胺基三氟化硫 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 57.0h， 生成 2,2-difluorooctanoic acid
  参考文献：
  名称：

  Amines That Transport Protons across Bilayer Membranes:  Synthesis, Lysosomal Neutralization, and Two-Phase pK_a Values by NMR

  摘要：

  It is desirable to be able to control the pH of lysosomes. A collection of lipophilic, nitrogenous bases, designed to act as membrane-active, catalytic proton transfer agents, were prepared and their effective pK(a)s measured in a vigorously stirred, two-phase system. One phase was a phosphate buffer whose pH was varied over the range ca, 1-11. The other was an immiscible, deuterated organic solvent in which the compounds preferentially resided even when protonated. When chemical shift changes versus the pH of the buffer were plotted, clear pK(a) curves were generated that are relevant to transmembrane proton transfer behavior. The two-phase pK(a)s increased with increasing counterion lipophilicity and with increasing organic solvent polarity, The compounds were also tested for their ability to neutralize the acidity of lysosomes, a model for other acidic vesicles involved in drug sorting. The most successful of these, imidazole 6a, has > 100 times the neutralizing power of ammonia, a standard lysosomotropic amine, causing a 1.7 unit rise in lysosomal pH of RAW cells at 0.1 mM, compared to a 0.2 and 1.4 unit rise for ammonium chloride at 0.1 and 10 mM, respectively.

  DOI：

  10.1021/jo960367f

文献信息

• A facile preparation method for α,α-difluoroalkanecarboxylic acids and esters. A formal difluoromethylene insertion to alkanecarboxylic acids using radical reaction
  作者：Takashi Okano、Nobuyuki Takakura、Yuko Nakano、Asako Okajima、Shoji Eguchi

  DOI：10.1016/0040-4020(94)01099-l

  日期：1995.2

  the photoreaction of a series of Barton esters reacted with 1,1-dichloro-2,2-difluoroethene to give radical adducts as the major product accompanied with self-trapping products. Primary, secondary, tertiary, benzyl, and some unsaturated alkyl radicals as well as those with another functional group such as ether, carbonyl, and azide were applicable. Barton esters of diacids also afford 1:2 adducts with

  通过一系列Barton酯的光反应生成的各种烷基自由基与1,1-二氯-2,2-二氟乙烯反应，生成自由基加合物作为主要产物，并伴有自捕获产物。伯，仲，叔，苄基和一些不饱和烷基以及具有另一官能团的那些如醚，羰基和叠氮化物是适用的。二元酸的巴顿酯还可以提供1：2加合物，以及少量的1：1加合物和双自陷产物（琥珀色情况除外）。这些加合物用AgNO 3 / H 2 O-THF水解为α，α-二氟链烷羧酸，并用AgNO 3甲醇水解。用/ MeOH制得相应的甲酯。将4-叠氮基-2，2-二氟丁酸和甲酯转化为二氟-GABA和二氟-γ-内酰胺。
• α,α-Difluroalkanecarboxylic acids: a general synthesis via alkyl radical addition to 1,1-dichloro-2,2-difluoroethylene
  作者：Takashi Okano、Nobuyuki Takakura、Yuko Nakano、Shoji Eguchi

  DOI：10.1016/s0040-4039(00)92671-6

  日期：1992.6

  Photodecomposition of alkanoic acid esters of N-hydroxy-2-thiopyridone with 1,1-dichloro-2,2-difuoroethylene gives alkyl-radical-trapped products, which give α,α-difluroalkanoic acids and their methyl esters on hydrolytic or methanolytic treatment with silver nitrate.

  N-羟基-2-硫代吡啶酮的链烷酸酯与1,1-二氯-2,2-二氟乙烯的光分解可得到烷基自由基所俘获的产物，在水解或甲醇解反应后，生成α，α-二氟链烷酸及其甲酯与硝酸银。
• Amines That Transport Protons across Bilayer Membranes:  Synthesis, Lysosomal Neutralization, and Two-Phase p<i>K</i>_a Values by NMR
  作者：Gene M. Dubowchik、Linda Padilla、Kurt Edinger、Raymond A. Firestone

  DOI：10.1021/jo960367f

  日期：1996.1.1

  It is desirable to be able to control the pH of lysosomes. A collection of lipophilic, nitrogenous bases, designed to act as membrane-active, catalytic proton transfer agents, were prepared and their effective pK(a)s measured in a vigorously stirred, two-phase system. One phase was a phosphate buffer whose pH was varied over the range ca, 1-11. The other was an immiscible, deuterated organic solvent in which the compounds preferentially resided even when protonated. When chemical shift changes versus the pH of the buffer were plotted, clear pK(a) curves were generated that are relevant to transmembrane proton transfer behavior. The two-phase pK(a)s increased with increasing counterion lipophilicity and with increasing organic solvent polarity, The compounds were also tested for their ability to neutralize the acidity of lysosomes, a model for other acidic vesicles involved in drug sorting. The most successful of these, imidazole 6a, has > 100 times the neutralizing power of ammonia, a standard lysosomotropic amine, causing a 1.7 unit rise in lysosomal pH of RAW cells at 0.1 mM, compared to a 0.2 and 1.4 unit rise for ammonium chloride at 0.1 and 10 mM, respectively.