4-methoxy-N-(2,2,2-trifluoro-1-phenylethylidene)aniline | 202869-51-0

• 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-methoxy-N-(2,2,2-trifluoro-1-phenylethylidene)aniline
• 英文别名: 4-methoxy-N-(2,2,2-trifluoro-1-phenylethylidene)benzenamine；N-[alpha-(Trifluoromethyl)benzylidene]-4-methoxyaniline；2,2,2-trifluoro-N-(4-methoxyphenyl)-1-phenylethanimine
• CAS: 202869-51-0
• 化学式: C₁₅H₁₂F₃NO
• 分子量: 279.262
• InChiKey: PQGWMIMWOGQFEQ-UHFFFAOYSA-N

物化性质

• 沸点：
  297.3±40.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  21.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-methoxy-N-(2,2,2-trifluoro-1-phenylethylidene)aniline 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 2.0h， 以69%的产率得到(4-methoxyphenyl)[2-(2-phenyl-1,1,1-trifluoroethyl)] amine
  参考文献：
  名称：

  Acyclic amides as estrogen receptor ligands: Synthesis, binding, activity and receptor interaction

  摘要：

  We have prepared a series of bisphenolic amides that mimic bibenzyl and homobibenzyl motifs commonly found as substructures in ligands for the estrogen receptor (ER). Representative members were prepared from three classes: N-phenyl benzamides, N-phenyl acetamides, and N-benzyl benzamides; in some cases the corresponding thiocarboxamides and sulfonamides were also prepared. Of these three classes, the N-phenyl benzamides had the highest affinity for ER, the N-phenyl acetamides had lower, and the N-benzyl benzamides were prone to fragmentation via a quinone methide intermediate. In the N-phenyl benzamide series, the highest affinity analogues had bulky N-substituents; a CF3 group, in particular, conferred high affinity. The thiocarboxamides bound better than the corresponding carboxamides and these bound better than the corresponding sulfonamides. Binding affinity comparisons suggest that the p-hydroxy group on the benzoate ring, which contributes most to the binding, is playing the role of the phenolic hydroxyl of estradiol. Computational studies and NMR and X-ray crystallographic analysis indicate that the two anilide systems studied have a strong preference for the s-cis or exo amide conformation, which places the two aromatic rings in a syn orientation. We used this structural template. together with the X-ray structure of the ER ligand binding domain, to elaborate an additional hydrogen bonding site on a benzamide system that elevated receptor binding further. When assayed on the individual ER subtypes, ER alpha and ER beta, these compounds show modest binding affinity preference for ER alpha. In a reporter gene transfection assay of transcriptional activity, the amides generally have full to nearly full agonist character on ERa, but have moderate to full antagonist character on ER beta. One high affinity carboxamide is 500-fold more potent as an agonist on ER alpha than on ER beta. This work illustrates that ER ligands having simple amide core structures can be readily prepared, but that high affinity binding requires an appropriate distribution of bulk, polarity, and functionality. The strong conformational preference of the core anilide function in all of these ligands defines a rather rigid geometry for further structural and functional expansion of these series. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00075-4
• 作为产物：
  描述：

  1-叠氮基-4-甲氧基苯 以 乙醚 、 苯 为溶剂， 反应 2.0h， 生成 4-methoxy-N-(2,2,2-trifluoro-1-phenylethylidene)aniline
  参考文献：
  名称：

  Acyclic amides as estrogen receptor ligands: Synthesis, binding, activity and receptor interaction

  摘要：

  We have prepared a series of bisphenolic amides that mimic bibenzyl and homobibenzyl motifs commonly found as substructures in ligands for the estrogen receptor (ER). Representative members were prepared from three classes: N-phenyl benzamides, N-phenyl acetamides, and N-benzyl benzamides; in some cases the corresponding thiocarboxamides and sulfonamides were also prepared. Of these three classes, the N-phenyl benzamides had the highest affinity for ER, the N-phenyl acetamides had lower, and the N-benzyl benzamides were prone to fragmentation via a quinone methide intermediate. In the N-phenyl benzamide series, the highest affinity analogues had bulky N-substituents; a CF3 group, in particular, conferred high affinity. The thiocarboxamides bound better than the corresponding carboxamides and these bound better than the corresponding sulfonamides. Binding affinity comparisons suggest that the p-hydroxy group on the benzoate ring, which contributes most to the binding, is playing the role of the phenolic hydroxyl of estradiol. Computational studies and NMR and X-ray crystallographic analysis indicate that the two anilide systems studied have a strong preference for the s-cis or exo amide conformation, which places the two aromatic rings in a syn orientation. We used this structural template. together with the X-ray structure of the ER ligand binding domain, to elaborate an additional hydrogen bonding site on a benzamide system that elevated receptor binding further. When assayed on the individual ER subtypes, ER alpha and ER beta, these compounds show modest binding affinity preference for ER alpha. In a reporter gene transfection assay of transcriptional activity, the amides generally have full to nearly full agonist character on ERa, but have moderate to full antagonist character on ER beta. One high affinity carboxamide is 500-fold more potent as an agonist on ER alpha than on ER beta. This work illustrates that ER ligands having simple amide core structures can be readily prepared, but that high affinity binding requires an appropriate distribution of bulk, polarity, and functionality. The strong conformational preference of the core anilide function in all of these ligands defines a rather rigid geometry for further structural and functional expansion of these series. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00075-4

文献信息

• Internally Reuse Waste: Catalytic Asymmetric One-Pot Strecker Reaction of Fluoroalkyl Ketones, Anilines and TMSCN by Sequential Catalysis
  作者：Yun-Lin Liu、Xiao-Ping Yin、Jian Zhou

  DOI：10.1002/cjoc.201800001

  日期：2018.4

  enantioselective one‐pot facile synthesis of fluorinated Cα‐tetrasubstituted amino nitriles from α‐fluoroalkyl α‐aryl ketones, anilines, and TMSCN through a sequential p‐TsOH catalyzed ketimine formation and chiral bifunctional tertiary amine mediated asymmetric Strecker reaction. This one‐pot approach has two important advantages. First, it greatly improves the overall yield of the synthesis of chiral Cα‐tetrasubstituted

  我们报告氟化的高度对映选择性的一锅简便合成Ç α -四取代的氨基腈从α氟烷基α -芳基酮，苯胺，和TMSCN通过顺序p -TsOH催化酮亚胺形成手性双官能叔胺介导的非对称的Strecker反应。这种单锅法有两个重要的优点。首先，它极大地提高了手性的合成的总收率Ç α -tetrasubstituted选自酮氟化的氨基腈，因为纯化α柱色谱法分析氟化酮亚胺的收率损失很大。其次，它代表了不对称串联反应的第一个例子，该例子可以同时重复使用上游步骤的副产物和催化剂作为促进剂和添加剂，分别提高后续催化对映选择性反应的反应性和对映选择性。它可以利用从酮亚胺形成步骤就地产生的副产物H 2 O活化TMSCN形成HCN，并同时重用剩余的p- TsOH酸作为添加剂以提高对映选择性。
• <i>N</i>-Protecting group tuning of the enantioselectivity in Strecker reactions of trifluoromethyl ketimines to synthesize quaternary α-trifluoromethyl amino nitriles by ion pair catalysis
  作者：Mengyuan Du、Longhui Yu、Ting Du、Zhaokun Li、Yueyang Luo、Xiangyu Meng、Zhengtao Tian、Changwu Zheng、Weiguo Cao、Gang Zhao

  DOI：10.1039/c9cc09151c

  日期：——

  trifluoromethylated quaternary stereocenters with N-PMP and unexplored N-Boc trifluoromethyl ketimines catalyzed using an organophosphine dual-reagent catalyst has been developed. The enantioselectivities of the corresponding products with the same catalyst could be switched by using different N-protecting groups (N-PMP or N-Boc). The trifluoromethyl amino nitriles were obtained in high yield and high enantioselectivity

  已开发出一种对映选择性斯特雷克反应，该反应可利用有机膦双试剂催化剂与N-PMP和未探索的N-Boc三氟甲基酮亚胺构建三氟甲基化的季立体中心。可以通过使用不同的N保护基（N-PMP或N-Boc）来切换相应产物与相同催化剂的对映选择性。在短时间内以高收率和高对映选择性获得了三氟甲基氨基腈，并且可以容易地将其转化为多种有用的含三氟甲基的化合物。
• Stereoselective metal-free catalytic synthesis of chiral trifluoromethyl aryl and alkyl amines
  作者：Andrea Genoni、Maurizio Benaglia、Elisabetta Massolo、Sergio Rossi

  DOI：10.1039/c3cc43821j

  日期：——

  The enantioselective organocatalytic reduction of trifluoromethyl aryl and alkyl ketoimines afforded the corresponding fluorinated amines with high chemical and stereochemical efficiency. The Lewis base catalyzed reaction with trichlorosilane led to chiral products with a trifluoromethyl group directly linked to the newly generated stereocenter typically in >90% yield and up to 98% e.e.

  三氟甲基芳基和烷基酮亚胺的对映选择性有机催化还原提供了具有高化学和立体化学效率的相应氟化胺。Lewis碱与三氯硅烷的催化反应生成具有三氟甲基的手性产物，该三氟甲基直接与新生成的立体中心相连，产率通常> 90％，ee最高可达98％
• Synthesis of β-CF₃ β-Amino Esters with an Indane Backbone by Rhenium-Catalyzed [3+2] Annulation
  作者：Tingjun Hu、Yuanqing Xu、Saisai Zhang、Heng-Ying Xiong、Guangwu Zhang

  DOI：10.1021/acs.orglett.0c03239

  日期：2020.11.20

  The [3+2] annulation of trifluoromethylated ketimines with acrylates has been enabled by rhenium-catalyzed C–H activation, delivering a variety of β-CF3 β-amino esters. The reaction has exhibited broad substrate generality regarding aromatic CF3-ketimines and acrylates, the ability for gram scale synthesis, and facile derivation of the annulation products. The transformation is one of the few examples

  三氟甲基化的酮亚胺与丙烯酸酯的[3 + 2]环已由铼催化C-H活化启用，提供各种β-CF的3 β氨基酯。该反应在芳族CF 3-酮亚胺和丙烯酸酯，克规模合成的能力以及环合产物的容易衍生方面表现出广泛的底物通用性。该转化是CF 3-酮亚胺的具有挑战性的sp 2 C–H键已被官能化的少数例子之一。通过这种策略快速组装具有生物学意义的重要氟化β-氨基酯将有益于相关研究，并启发了一种新的氟化基序合成方法。
• Chiral Phosphoric Acid Catalyzed Transfer Hydrogenation: Facile Synthetic Access to Highly Optically Active Trifluoromethylated Amines
  作者：Alexander Henseler、Masanori Kato、Keiji Mori、Takahiko Akiyama

  DOI：10.1002/anie.201103240

  日期：2011.8.22

  Amines to an end: Highly optically active α‐CF3‐functionalized amines can be obtained using metal‐free reaction conditions. The method involves the transfer hydrogenation of CF3‐substituted ketimines catalyzed by 1 and reductive amination of CF3‐substituted ketones. The synthetic utility of this method was demonstrated by the synthesis of a CF3 analogue of NPS R‐568. PMP=para‐methoxyphenyl.

  胺结束：高度光学活性α - CF 3 -官能化的胺可以用不含金属的反应条件来获得。该方法涉及CF的转移氢化3吨通过催化取代酮亚胺1 CF的和还原性胺化3 -取代的酮。通过合成NPS R-568的CF 3类似物证明了该方法的合成效用。PMP =对甲氧基苯基