4-fluoro-3'-trifluoromethylbenzophenone | 16574-51-9

• 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: 4-fluoro-3'-trifluoromethylbenzophenone
• 英文别名: m-Trifluormethyl-p'-fluorbenzophenon；p-Fluor-m'-trifluormethylbenzophenon；4-Fluoro-3'-(trifluoromethyl)benzophenone；(4-fluorophenyl)-[3-(trifluoromethyl)phenyl]methanone
• CAS: 16574-51-9
• 化学式: C₁₄H₈F₄O
• mdl: MFCD12541608
• 分子量: 268.211
• InChiKey: MEQKQSVVVZYOJY-UHFFFAOYSA-N

物化性质

• 熔点：
  44-45 °C(Solv: ethanol (64-17-5))
• 沸点：
  80-82 °C(Press: 0.07 Torr)
• 密度：
  1.306±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-fluoro-3'-trifluoromethylbenzophenone 在 sodium tetrahydroborate 、 氯化亚砜 作用下， 生成 1-[Chloro-(4-fluorophenyl)methyl]-3-(trifluoromethyl)benzene
  参考文献：
  名称：

  CoMFA Study of Novel Phenyl Ring-Substituted 3α-(Diphenylmethoxy)tropane Analogues at the Dopamine Transporter

  摘要：

  A series of phenyl ring-substituted analogues of 3 alpha-(diphenylmethoxy)tropane (benztropine) has been prepared as novel probes for the dopamine transporter. Cross-validated comparative molecular field analysis (CoMFA) models of the binding domain on the dopamine transporter were constructed using 37 geometry-optimized structures of these compounds and their corresponding binding affinities (Ki values) for the displacement of [H-3]WIN 35,428 or potency of [H-3]dopamine uptake inhibition (IC50 values) in rat caudate putamen tissue. The most predictive model (q(2) = 0.78) correlated the steric component of CoMFA to the dependent variable of [H-3]WIN 35,428 binding affinities. A novel series of seven phenyl ring-substituted analogues of 3a-(diphenylmethoxy)tropane was prepared, and our best molecular model was used to accurately predict their binding affinities. This study is the first to provide a CoMFA model for this class of dopamine uptake inhibitors. This model represents an advancement in the design of novel dopamine transporter ligands, based on 3a-(diphenylmethoxy)tropane, and further substantiates structure-activity relationships that have previously been proposed for this class of compounds. This CoMFA model can now be used to predict the binding affinities of novel 3a-(diphenylmethoxy)tropane analogues at the dopamine transporter and will be useful in the design of molecular probes within this class of dopamine uptake inhibitors.

  DOI：

  10.1021/jm980701v
• 作为产物：
  描述：

  benzene(diazonium) tetrakis(3,5-bis(trifluoromethyl)phenyl)borate 在 氧气 作用下， 以 various solvent(s) 为溶剂， 以55%的产率得到氟苯
  参考文献：
  名称：

  芳基碳正离子对 C-F 键的活化：溶液中碳原子之间的决定性分子内氟化物转移和分子间氟化物离子提取的第一个例子

  摘要：

  由于碳氟化合物在科学和商业上的重要性，选择性 CF 键活化的化学反应引起了广泛关注。1 然而，迄今为止，溶液中 CF 键活化的研究通常涉及过渡金属配合物或碱金属。作为 CF 键活化的新方法的一部分，我们对使用碳正离子通过三中心过渡态或中间体从有机分子中提取氟化物的可能性感兴趣。尽管 Morton 在工作中的气相中记录了涉及高价 [CFC]+ 相互作用的阳离子氟化物转移，2 但溶液中这种分子间提取的报告实际上并不存在，并且已发表的分子内转移案例充满争议。 3 事实上，氟化物在溶液中是否会发生这种变化的问题一直是争论的焦点。在这篇文章中，我们描述了溶液中碳原子之间的分子内氟化物位移（方案 1）以及第一个记录在案的芳基阳离子与其反离子之间的类似分子间氟化物提取的例子。在气相中，由于没有溶剂，碳正离子的反应性会增强；2 在溶液中，必须产生反应性相对较高的阳离子，以提供氟化物转移的驱动力。最好在非亲

  DOI：

  10.1021/ja963090+

文献信息

• Electrophilic Aromatic Aroylation with CF₃‐Bearing Arenecarboxylic Acid Derivatives: Reaction Behavior and Acidic Mediator Dependence
  作者：Okamoto Akiko、Maeyama Katsuya、Oike Hideaki、Yonezawa Noriyuki

  DOI：10.1080/00397910701465479

  日期：2007.8

  Abstract Triflic acid (TfOH) has been proven to be effective as a tolerant acidic mediator in electrophilic aromatic aroylation with CF3‐bearing aroyl chlorides. The TfOH‐mediated aroylation of fluorobenzene proceeds with high selectivity to give CF3‐bearing aryl fluorophenyl ketones in good yields, which are hardly obtained with the aid of AlCl3 or direct condensation reagents.

  摘要 三氟甲磺酸 (TfOH) 已被证明在与含 CF3 的芳酰氯进行亲电芳族芳酰化反应中作为一种耐受酸性介质是有效的。TfOH 介导的氟苯芳酰化反应以高选择性进行，以良好的收率得到带有 CF3 的芳基氟苯基酮，这在 AlCl3 或直接缩合试剂的帮助下很难获得。
• A novel Brønsted acid catalyst for Friedel–Crafts acylation
  作者：Anna G. Posternak、Romute Yu. Garlyauskayte、Lev M. Yagupolskii

  DOI：10.1016/j.tetlet.2008.11.038

  日期：2009.1

  Bis(trifluoroalkylsulfonylimino)trifluoromethanesulfonic acid has demonstrated remarkable catalytic ability in the electrophilic acylation of aromatic substrates. Various perfluoroalkyl substituted aroyl chlorides are employed in Friedel–Crafts acylation typically using 1 mol % of catalyst.

  在芳族底物的亲电子酰化反应中，双（三氟烷基磺酰亚胺基）三氟甲磺酸已显示出显着的催化能力。在Friedel-Crafts酰化反应中，通常使用1 mol％的催化剂使用各种全氟烷基取代的芳酰氯。
• C−F Bond Activation by Aryl Carbocations:  Conclusive Intramolecular Fluoride Shifts between Carbon Atoms in Solution and the First Examples of Intermolecular Fluoride Ion Abstractions
  作者：Dana Ferraris、Christopher Cox、Rahul Anand、Thomas Lectka

  DOI：10.1021/ja963090+

  日期：1997.5.1

  examples of analogous intermolecular fluoride abstractions between an aryl cation and its counterion. In the gas phase the reactivity of carbocations is enhanced by the absence of solvent;2 in solution, cations of comparably high reactivity must be generated to provide the driving force for fluoride transfers. It would also be best to generate the carbocations in nonnucleophilic media, employing substrates

  由于碳氟化合物在科学和商业上的重要性，选择性 CF 键活化的化学反应引起了广泛关注。1 然而，迄今为止，溶液中 CF 键活化的研究通常涉及过渡金属配合物或碱金属。作为 CF 键活化的新方法的一部分，我们对使用碳正离子通过三中心过渡态或中间体从有机分子中提取氟化物的可能性感兴趣。尽管 Morton 在工作中的气相中记录了涉及高价 [CFC]+ 相互作用的阳离子氟化物转移，2 但溶液中这种分子间提取的报告实际上并不存在，并且已发表的分子内转移案例充满争议。 3 事实上，氟化物在溶液中是否会发生这种变化的问题一直是争论的焦点。在这篇文章中，我们描述了溶液中碳原子之间的分子内氟化物位移（方案 1）以及第一个记录在案的芳基阳离子与其反离子之间的类似分子间氟化物提取的例子。在气相中，由于没有溶剂，碳正离子的反应性会增强；2 在溶液中，必须产生反应性相对较高的阳离子，以提供氟化物转移的驱动力。最好在非亲
• CoMFA Study of Novel Phenyl Ring-Substituted 3α-(Diphenylmethoxy)tropane Analogues at the Dopamine Transporter
  作者：Amy Hauck Newman、Sari Izenwasser、Michael J. Robarge、Richard H. Kline

  DOI：10.1021/jm980701v

  日期：1999.9.1

  A series of phenyl ring-substituted analogues of 3 alpha-(diphenylmethoxy)tropane (benztropine) has been prepared as novel probes for the dopamine transporter. Cross-validated comparative molecular field analysis (CoMFA) models of the binding domain on the dopamine transporter were constructed using 37 geometry-optimized structures of these compounds and their corresponding binding affinities (Ki values) for the displacement of [H-3]WIN 35,428 or potency of [H-3]dopamine uptake inhibition (IC50 values) in rat caudate putamen tissue. The most predictive model (q(2) = 0.78) correlated the steric component of CoMFA to the dependent variable of [H-3]WIN 35,428 binding affinities. A novel series of seven phenyl ring-substituted analogues of 3a-(diphenylmethoxy)tropane was prepared, and our best molecular model was used to accurately predict their binding affinities. This study is the first to provide a CoMFA model for this class of dopamine uptake inhibitors. This model represents an advancement in the design of novel dopamine transporter ligands, based on 3a-(diphenylmethoxy)tropane, and further substantiates structure-activity relationships that have previously been proposed for this class of compounds. This CoMFA model can now be used to predict the binding affinities of novel 3a-(diphenylmethoxy)tropane analogues at the dopamine transporter and will be useful in the design of molecular probes within this class of dopamine uptake inhibitors.