(4-methoxyphenyl)[2-(2-phenyl-1,1,1-trifluoroethyl)] amine | 191084-78-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4-methoxyphenyl)[2-(2-phenyl-1,1,1-trifluoroethyl)] amine
• 英文别名: 4-methoxy-N-(2,2,2-trifluoro-1-phenylethyl)aniline；N-(2,2,2-trifluoro-1-phenylethyl)-4-methoxyaniline；N-(1,1,1-trifluoro-2-phenethyl)-4-methoxyaniline；4-methoxy-N-(2,2,2-trifluorophenylethyl)aniline；N-[alpha-(Trifluoromethyl)benzyl]-4-methoxyaniline
• CAS: 191084-78-3
• 化学式: C₁₅H₁₄F₃NO
• 分子量: 281.277
• InChiKey: GJZHXGIKVUBJFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-methoxyphenyl)[2-(2-phenyl-1,1,1-trifluoroethyl)] amine 在 劳森试剂 、 吡啶 、 potassium carbonate 作用下， 以 甲苯 为溶剂， 反应 8.0h， 生成 4-Methoxy-N-(4-methoxy-phenyl)-N-(2,2,2-trifluoro-1-phenyl-ethyl)-thiobenzamide
  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：

  N-苄基-4-甲氧基苯胺 在 palladium on activated charcoal sodium tungstate 、 potassium tert-butylate 、 双氧水 、 ammonium formate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 54.0h， 生成 (4-methoxyphenyl)[2-(2-phenyl-1,1,1-trifluoroethyl)] amine
  参考文献：
  名称：

  通过硝酮的亲核三氟甲基化作用生成的α-（三氟甲基）胺衍生物。

  摘要：

  （三氟甲基）三甲基硅烷（TMSCF（3））与硝酮反应，得到保护为O-三甲基甲硅烷基醚的α-（三氟甲基）羟胺。叔丁醇钾引发亲核三氟甲基化。该反应与α，N-二芳基硝酮最有效，并且条件与芳基上的一系列取代基相容。硝酸/ TMSCF（3）加合物的酸性脱保护生成α-（三氟甲基）羟胺。加合物的催化氢化产生α-（三氟甲基）胺。在α-芳基环或杂环α-芳基上具有强吸电子基团的Nitrone / TMSCF（3）加合物经历消除/加成序列以生成α，α-双（三氟甲基）胺。烷基直接与1,3-偶极部分结合的亚硝基无法与TMSCF（3）反应，

  DOI：

  10.1021/jo000685l

文献信息

• Enantioselective Pd-Catalyzed Hydrogenation of Fluorinated Imines: Facile Access to Chiral Fluorinated Amines
  作者：Mu-Wang Chen、Ying Duan、Qing-An Chen、Duo-Sheng Wang、Chang-Bin Yu、Yong-Gui Zhou

  DOI：10.1021/ol1020256

  日期：2010.11.5

  An enantioselective hydrogenation of simple fluorinated imines has been developed using Pd(OCOCF3)2/(R)-Cl-MeO-BIPHEP as a catalyst, and up to 94% ee was achieved. This method provides an efficient route to enantioenriched fluorinated amines.

  使用Pd（OCOCF 3）2 /（R）-Cl-MeO-BIPHEP作为催化剂，开发了一种简单的氟化亚胺的对映体选择性氢化反应，可实现高达94％的ee。该方法提供了对映体富集的氟化胺的有效途径。
• 一种三氟甲基化酮的还原胺化反应制备三氟 乙胺衍生物的方法
  申请人：浙江大学

  公开号：CN105503818B

  公开（公告）日：2017-11-17

  本发明公开了一种三氟甲基化酮的还原胺化反应制备三氟乙胺衍生物方法。它是以三氟甲基化酮和对甲氧基苯胺为原料，以有机氢供体为还原剂，在酸性催化剂存在下，在有机溶剂中加热反应获得三氟乙胺衍生物。本发明反应条件温和，工艺简单，操作便捷；所得三氟乙胺衍生物有潜在的良好的生物活性，并可以作为有机合成中间体使用。
• Palladium(II)-Catalyzed Enantioselective Synthesis of α-(Trifluoromethyl)arylmethylamines
  作者：Thomas Johnson、Mark Lautens

  DOI：10.1021/ol401862g

  日期：2013.8.16

  [GRAPHICS]Trifluoromethylacetaldimines, generated in situ from the corresponding N,O-acetals, undergo 1,2-addition of arylboroxines under palladium(II) catalysis to generate a variety of alpha-(trifluoromethyl)arylmethylamines with good to high enantioselectivity (up to 97% ee). The pyridine-oxazolidine (PyOX) class of ligands was found to be particularly suitable for this transformation, which proceeds without exclusion of ambient air and moisture.
• Preparation of Tri- and Difluoromethylated Amines from Aldimines Using (Trifluoromethyl)trimethylsilane
  作者：G. K. Surya Prakash、Ryo Mogi、George A. Olah

  DOI：10.1021/ol061357w

  日期：2006.8.1

  Addition of a trifluoromethyl group into aldimines was accomplished using ( trifluoromethyl) trimethylsilane with tetraalkylammonium fluorides as initiators, and the resulting adducts were converted to difluoromethylated imines in the presence of excess fluoride. The imines were reduced to difluoromethylated amines using sodium borohydride.
• Novel and effective synthesis of trifluoromethylated amines by use of an combination
  作者：Yasuo Yokoyama、Kunio Mochida

  DOI：10.1016/s0040-4039(97)00641-2

  日期：1997.5

  Efficient synthesis of trifluoromethylated amine derivatives by use of an Et3GeNa/C6H5SCF3 combination is described. This reaction proceeded smoothly to give the desired compound in excellent yield. (C) 1997 Elsevier Science Ltd.