3-(trifluoromethyl)-2,5-hexanedione | 334865-24-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(trifluoromethyl)-2,5-hexanedione
• 英文别名: 3-(Trifluoromethyl)hexane-2,5-dione；3-(trifluoromethyl)hexane-2,5-dione
• CAS: 334865-24-6
• 化学式: C₇H₉F₃O₂
• 分子量: 182.142
• InChiKey: PMSAGFITTMDSET-UHFFFAOYSA-N

物化性质

• 沸点：
  181.7±35.0 °C(predicted)
• 密度：
  1.174±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(trifluoromethyl)-2,5-hexanedione 在 N,N'-二环己基碳二亚胺 、 cesium fluoride 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 4.0h， 生成 2-(2,5-dimethyl-3-(trifluoromethyl)pyrrol-1-yl)acetic acid N-hydroxysuccinimide ester
  参考文献：
  名称：

  3-（三氟甲基）-2,5-己二酮使蛋白质发生交联。模型研究表明，意想不到的胺依赖性脱氟取代途径与吡咯形成竞争。

  摘要：

  研究了神经毒性γ-二酮3-甲基-2,5-己二酮（3-MHD）及其类似物3-（三氟甲基）-2,5-己二酮（3-TFMHD）对蛋白质的修饰作用。与3-MHD形成基于赖氨酸的吡咯并导致自氧化依赖的蛋白质交联不同，3-TFMHD形成自氧化惰性的吡咯。3-TFFMD在交联核糖核酸酶A方面仍然与3-MHD一样有效，这一令人惊讶的发现表明，蛋白质赖氨酸与3-TFFMD的缩合可以替代与吡咯形成竞争的过程。使用新戊胺进行的模型研究导致分离出预期的1-（2,2-二甲基丙基）-2,5-二甲基-3-（三氟甲基）吡咯以及新戊胺-3-TFMHD 2：1加合物N，N' -双（2,2-二甲基丙基）-2-氨基-3-乙酰基-5-甲基吡咯（主要）和N，N'-双（2，2-二甲基丙基）-3-（1-氨基亚乙基）-5-甲基-4-吡咯啉-2-酮（次要）。提议通过席夫碱形成，烯胺氟化物消除，第二胺缩合和水解进行这些2：1加合物的形成，据认

  DOI：

  10.1021/jo011101y
• 作为产物：
  描述：

  5-nitro-4-(trifluoromethyl)-2-hexanone 在 氢氧化钾 、 potassium permanganate 、 magnesium sulfate 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 以69%的产率得到3-(trifluoromethyl)-2,5-hexanedione
  参考文献：
  名称：

  Novel 2,5-Hexanedione Analogues. Substituent-Induced Control of the Protein Cross-Linking Potential and Oxidation Susceptibility of the Resulting Primary Amine-Derived Pyrroles

  摘要：

  The neurotoxic gamma -diketone, 2,5-hexanedione (2,5-HD), induces neurofilamentous swellings at prenodal sites in proximal axons as a consequence of pyrrolation of lysine E-amino groups on neurofilament proteins. However, there is disagreement as to whether pyrrole formation and the associated alteration of noncovalent interactions is sufficient to cause neurofilament accumulation, or whether pyrrole autoxidation and subsequent protein-protein cross-linking is an obligatory event. To investigate gamma -diketones that might form pyrroles inert to autoxidative-induced cross-linking, we synthesized 1,1,1-trifluoro-2,5-hexanedione, 3-(trifluoromethyl)-2,5-hexanedione (3-TFMHD), and two 3-(dialkylaminocarbonyl)-2,5-diketones and assessed their rates of pyrrole formation with amines, the oxidation susceptibility of the resulting pyrroles, and the protein cross-linking potential in vitro, relative to those of 3-methyl-2,5-hexanedione. 1,1,1-Trifluoro-2,5-hexanedione does not form pyrroles, but the three 2,5-HD analogues with an electron-withdrawing 3-substituent all rapidly formed pyrroles that were inert to autoxidation. Although 3-TMFHD nonetheless still induced cross-linking of ribonuclease A, by a nonoxidative mechanism independent of the pyrrole, the two 3-(dialkylaninocarbonyl)-2,5-diketones did not exhibit any protein cross-linking. As these two gamma -diketones possess aqueous-organic partitioning properties similar to those of 2,5-HD, they should serve as useful mechanistic probes in further studies.

  DOI：

  10.1021/tx000169q

文献信息

• Novel 2,5-Hexanedione Analogues. Substituent-Induced Control of the Protein Cross-Linking Potential and Oxidation Susceptibility of the Resulting Primary Amine-Derived Pyrroles
  作者：Guozhang Xu、Malvinder P. Singh、Damodaragounder Gopal、Lawrence M. Sayre

  DOI：10.1021/tx000169q

  日期：2001.3.1

  The neurotoxic gamma -diketone, 2,5-hexanedione (2,5-HD), induces neurofilamentous swellings at prenodal sites in proximal axons as a consequence of pyrrolation of lysine E-amino groups on neurofilament proteins. However, there is disagreement as to whether pyrrole formation and the associated alteration of noncovalent interactions is sufficient to cause neurofilament accumulation, or whether pyrrole autoxidation and subsequent protein-protein cross-linking is an obligatory event. To investigate gamma -diketones that might form pyrroles inert to autoxidative-induced cross-linking, we synthesized 1,1,1-trifluoro-2,5-hexanedione, 3-(trifluoromethyl)-2,5-hexanedione (3-TFMHD), and two 3-(dialkylaminocarbonyl)-2,5-diketones and assessed their rates of pyrrole formation with amines, the oxidation susceptibility of the resulting pyrroles, and the protein cross-linking potential in vitro, relative to those of 3-methyl-2,5-hexanedione. 1,1,1-Trifluoro-2,5-hexanedione does not form pyrroles, but the three 2,5-HD analogues with an electron-withdrawing 3-substituent all rapidly formed pyrroles that were inert to autoxidation. Although 3-TMFHD nonetheless still induced cross-linking of ribonuclease A, by a nonoxidative mechanism independent of the pyrrole, the two 3-(dialkylaninocarbonyl)-2,5-diketones did not exhibit any protein cross-linking. As these two gamma -diketones possess aqueous-organic partitioning properties similar to those of 2,5-HD, they should serve as useful mechanistic probes in further studies.
• Cross-Linking of Proteins by 3-(Trifluoromethyl)-2,5-hexanedione. Model Studies Implicate an Unexpected Amine-Dependent Defluorinative Substitution Pathway Competing with Pyrrole Formation
  作者：Guozhang Xu、Lawrence M. Sayre

  DOI：10.1021/jo011101y

  日期：2002.5.1

  Protein modification by the neurotoxic gamma-diketone 3-methyl-2,5-hexanedione (3-MHD) and its analogue 3-(trifluoromethyl)-2,5-hexanedione (3-TFMHD) was examined. Unlike 3-MHD, which forms lysine-based pyrroles that lead to autoxidation-dependent protein cross-linking, 3-TFMHD forms an autoxidatively inert pyrrole. The surprising finding that 3-TFMHD was nonetheless as effective as 3-MHD in cross-linking

  研究了神经毒性γ-二酮3-甲基-2,5-己二酮（3-MHD）及其类似物3-（三氟甲基）-2,5-己二酮（3-TFMHD）对蛋白质的修饰作用。与3-MHD形成基于赖氨酸的吡咯并导致自氧化依赖的蛋白质交联不同，3-TFMHD形成自氧化惰性的吡咯。3-TFFMD在交联核糖核酸酶A方面仍然与3-MHD一样有效，这一令人惊讶的发现表明，蛋白质赖氨酸与3-TFFMD的缩合可以替代与吡咯形成竞争的过程。使用新戊胺进行的模型研究导致分离出预期的1-（2,2-二甲基丙基）-2,5-二甲基-3-（三氟甲基）吡咯以及新戊胺-3-TFMHD 2：1加合物N，N' -双（2,2-二甲基丙基）-2-氨基-3-乙酰基-5-甲基吡咯（主要）和N，N'-双（2，2-二甲基丙基）-3-（1-氨基亚乙基）-5-甲基-4-吡咯啉-2-酮（次要）。提议通过席夫碱形成，烯胺氟化物消除，第二胺缩合和水解进行这些2：1加合物的形成，据认