methyl 2-cyano-3-(4-trifluoromethylphenyl)propionate | 676272-24-5

• 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: methyl 2-cyano-3-(4-trifluoromethylphenyl)propionate
• 英文别名: Methyl 2-cyano-3-(4-trifluoromethylphenyl)propionate；methyl 2-cyano-3-[4-(trifluoromethyl)phenyl]propanoate
• CAS: 676272-24-5
• 化学式: C₁₂H₁₀F₃NO₂
• 分子量: 257.212
• InChiKey: KKUBBWIUMFESNZ-UHFFFAOYSA-N

物化性质

• 沸点：
  336.4±37.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-cyano-3-(4-trifluoromethylphenyl)propionate 在 水 、 氢气 、 sodium methylate 、 溶剂黄146 、 三乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 20.0~100.0 ℃ 、100.0 kPa 条件下， 反应 156.33h， 生成 2-[[(2-Methylpropan-2-yl)oxycarbonylamino]methyl]-3-[4-(trifluoromethyl)phenyl]-2-[[4-(trifluoromethyl)phenyl]methyl]propanoic acid
  参考文献：
  名称：

  Synthesis of Cationic Antimicrobial β^2,2-Amino Acid Derivatives with Potential for Oral Administration

  摘要：

  We have prepared a series of highly potent achiral cationic beta(2,2)-amino acid derivatives that fulfill the Lipinski's rule of five and that contain the basic structural requirements of short cationic antimicrobial peptides. Highest antimicrobial potency was observed for one of the smallest beta(2,2)-amino acid derivatives (M-w 423.6) exhibiting a MIC of 3.8 mu M against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and Staphylococcus aureus, and 7.7 mu M against Escherichia coli. The beta(2,2)-amino acid derivatives were shown to have similar absorption properties as several commercially available drugs, and the results implied a resembling membrane disrupting mechanism of action as reported for much larger cationic antimicrobial peptides. By their high potency, nontoxicity, absorption properties, and ease of synthesis, the beta(2,2)-amino acid derivatives demonstrate a way to modify a vastly investigated class of cationic antimicrobial peptides into small drug-like molecules with high commercial potential.

  DOI：

  10.1021/jm101327d
• 作为产物：
  描述：

  对三氟甲基苯甲醛 在 aluminum oxide 、 ammonia borane 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 methyl 2-cyano-3-(4-trifluoromethylphenyl)propionate
  参考文献：
  名称：

  供体-受体对之间光介导的单电子转移直接对α-氰基β-芳烃进行环丙烷化

  摘要：

  传统上，环丙烷是通过将卡宾或基于自由基的C1单元正式加成至烯烃中而制备的[2 + 1]。相比之下，氧化还原活性C1单元对烷烃的单锅分子间环丙烷化作用尚未实现。在此，我们仅通过将β-芳基丙腈和C1自由基前体（N-氧基酯）暴露于碱性和蓝光下即可实现此过程。整个过程是氧化还原中性的，不需要金属或有机基光催化剂。我们的发现支持单电子从丙腈的α-氰基碳负离子向N的单电子转移（SET）蓝酸酯通过其电子给体-受体（EDA）络合物促进了羟氧基酯的合成。这样形成的α-氰基碳自由基会失去一个β-质子，形成一个π共振稳定的自由基阴离子，该阴离子优先在苄基β-位与脱羧的C1自由基单元偶联。这种新的无过渡金属化学物质可耐受富电子和电子不足的（杂）芳基体系，甚至具有硫化物或烯烃官能度，从而提供一系列带有拥挤的四取代季碳的顺-芳基/氰基环丙烷。

  DOI：

  10.1002/chem.202100341

文献信息

• Superacid-Catalyzed Intramolecular Cyclization Reaction of Arylcyanopropionate: <i>Geminal</i> Substitution Effect on Superelectrophilicity
  作者：Satoshi Nakamura、Hiromichi Sugimoto、Tomohiko Ohwada

  DOI：10.1021/jo800674h

  日期：2008.6.1

  α-proton in the cyclization process. The acidity dependence of the cyclization reactions and 13C NMR studies of a model compound, methyl cyanoacetate, in various acidic media were consistent with the involvement of the O,N-diprotonated dication of methyl cyanoacetate, a distonic dication, in strong acid, and this is considered to be the de facto electrophile in the present cyclization reaction of arylcyanopropionates

  我们介绍了芳基氰基丙酸酯的超强酸催化的分子内环化反应，以中等至高收率得到环化的五元和六元β-烯胺酯。质子化的腈与芳族碳原子的已知分子内闭环反应限于6元情况。有趣的是，观察到的氰基官能度反应性的显著协同增加，和氰基的氮原子被转化成氨基，当酯基存在于一个孪位的布置。氘交换实验排除了α-质子去质子化在环化过程中的参与。环化反应和13的酸度依赖性在各种酸性介质中对模型化合物氰基乙酸甲酯的13 C NMR研究与强酸中氰基乙酸甲酯的O，N-二质子化指示剂（二元体指示剂）在强酸中的参与一致，这被认为是事实上的亲电子试剂。在本发明的芳基氰基丙酸酯的环化反应中。
• Reductive alkylation of active methylene compounds with carbonyl derivatives, calcium hydride and a heterogeneous catalyst
  作者：Carole Guyon、Marie-Christine Duclos、Marc Sutter、Estelle Métay、Marc Lemaire

  DOI：10.1039/c5ob00849b

  日期：——

  A one-pot two-step reaction (Knoevenagel condensation – reduction of the double bond) has been developed using calcium hydride as a reductant in the presence of a supported noble metal catalyst. The reaction between carbonyl compounds and active methylene compounds such as methylcyanoacetate, 1,3-dimethylbarbituric acid, dimedone and the more challenging dimethylmalonate, affords the corresponding

  在负载型贵金属催化剂存在下，使用氢化钙作为还原剂，开发了一种一锅两步反应（Knoevenagel缩合-双键还原）。羰基化合物与活性亚甲基化合物（例如氰基乙酸甲酯，1,3-二甲基巴比妥酸，二甲酮和更具挑战性的丙二酸二甲酯）之间的反应可提供中等至良好收率（最高83％）的相应单烷基化产物，且起始羰基化合物的减少极少化合物。
• Atom- and Step-Economical Preparation of Reduced Knoevenagel Adducts Using CO as a Deoxygenative Agent
  作者：Pavel N. Kolesnikov、Dmitry L. Usanov、Evgeniya A. Barablina、Victor I. Maleev、Denis Chusov

  DOI：10.1021/ol502424t

  日期：2014.10.3

  A highly efficient one-step Rh-catalyzed preparation of reduced Knoevenagel adducts of various aldehydes and ketones with active methylene compounds has been developed. The protocol does not require an external hydrogen source and employs carbon monoxide as a deoxygenative agent. The use of malonic acid or cyanoacetamide enabled efficient formal deoxygenative addition of methyl acetate or acetonitrile to aldehydes. The developed methodology was applied to the synthesis of the precursors of biomedically important compounds.
• Direct Cyclopropanation of α‐Cyano β‐Aryl Alkanes by Light‐Mediated Single Electron Transfer Between Donor–Acceptor Pairs
  作者：Jing Li、Martin J. Lear、Yujiro Hayashi

  DOI：10.1002/chem.202100341

  日期：2021.4

  formal [2+1] addition of carbene or radical based C1 units to alkenes. In contrast, the one‐pot intermolecular cyclopropanation of alkanes by redox active C1 units has remained unrealised. Herein, we achieved this process simply by exposing β‐aryl propionitriles and C1 radical precursors (N‐oxy esters) to base and blue light. The overall process is redox‐neutral and a photocatalyst, whether metal‐ or organic‐based

  传统上，环丙烷是通过将卡宾或基于自由基的C1单元正式加成至烯烃中而制备的[2 + 1]。相比之下，氧化还原活性C1单元对烷烃的单锅分子间环丙烷化作用尚未实现。在此，我们仅通过将β-芳基丙腈和C1自由基前体（N-氧基酯）暴露于碱性和蓝光下即可实现此过程。整个过程是氧化还原中性的，不需要金属或有机基光催化剂。我们的发现支持单电子从丙腈的α-氰基碳负离子向N的单电子转移（SET）蓝酸酯通过其电子给体-受体（EDA）络合物促进了羟氧基酯的合成。这样形成的α-氰基碳自由基会失去一个β-质子，形成一个π共振稳定的自由基阴离子，该阴离子优先在苄基β-位与脱羧的C1自由基单元偶联。这种新的无过渡金属化学物质可耐受富电子和电子不足的（杂）芳基体系，甚至具有硫化物或烯烃官能度，从而提供一系列带有拥挤的四取代季碳的顺-芳基/氰基环丙烷。
• Synthesis of Cationic Antimicrobial β^2,2-Amino Acid Derivatives with Potential for Oral Administration
  作者：Terkel Hansen、Dominik Ausbacher、Gøril E. Flaten、Martina Havelkova、Morten B. Strøm

  DOI：10.1021/jm101327d

  日期：2011.2.10

  We have prepared a series of highly potent achiral cationic beta(2,2)-amino acid derivatives that fulfill the Lipinski's rule of five and that contain the basic structural requirements of short cationic antimicrobial peptides. Highest antimicrobial potency was observed for one of the smallest beta(2,2)-amino acid derivatives (M-w 423.6) exhibiting a MIC of 3.8 mu M against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and Staphylococcus aureus, and 7.7 mu M against Escherichia coli. The beta(2,2)-amino acid derivatives were shown to have similar absorption properties as several commercially available drugs, and the results implied a resembling membrane disrupting mechanism of action as reported for much larger cationic antimicrobial peptides. By their high potency, nontoxicity, absorption properties, and ease of synthesis, the beta(2,2)-amino acid derivatives demonstrate a way to modify a vastly investigated class of cationic antimicrobial peptides into small drug-like molecules with high commercial potential.