N-(2,2,2-trifluoro-1-phenylethyl)aniline | 191084-66-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(2,2,2-trifluoro-1-phenylethyl)aniline
• 英文别名: N-[alpha-(Trifluoromethyl)benzyl]aniline
• CAS: 191084-66-9
• 化学式: C₁₄H₁₂F₃N
• mdl: MFCD19089247
• 分子量: 251.251
• InChiKey: LEIIGGMIXIBLGP-UHFFFAOYSA-N

物化性质

• 沸点：
  65-67 °C(Press: 0.04 Torr)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2,2,2-trifluoro-1-phenylethyl)aniline 在 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 邻二氯苯 为溶剂， 反应 16.0h， 生成 4-hydroxy-N-phenyl-N-(2,2,2-trifluoro-1-phenylethyl)benzamide
  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：

  苯基羟胺 在 palladium on activated charcoal potassium tert-butylate 、 ammonium formate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 55.0h， 生成 N-(2,2,2-trifluoro-1-phenylethyl)aniline
  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

• H ₂ Activation by Non‐Transition‐Metal Systems: Hydrogenation of Aldimines and Ketimines with LiN(SiMe ₃ ) ₂
  作者：Daniel C. Elliott、Alex Marti、Pablo Mauleón、Andreas Pfaltz

  DOI：10.1002/chem.201805549

  日期：2019.2.6

  In recent years, H2 activation at non‐transition‐metal centers has met with increasing attention. Here, a system in which H2 is activated and transferred to aldimines and ketimines using substoichiometric amounts of lithium bis(trimethylsilyl)amide is reported. Notably, the reaction tolerates the presence of acidic protons in the α‐position. Mechanistic investigations indicated that the reaction proceeds

  近年来，非过渡金属中心的H 2活化受到越来越多的关注。在此，报道了使用亚化学计量的双（三甲基甲硅烷基）氨基锂将H 2活化并转移至醛亚胺和酮亚胺的系统。值得注意的是，该反应可耐受α位酸性质子的存在。机理研究表明，反应通过氢化锂中间体作为实际的还原剂进行。
• TTMPP-catalyzed trifluoromethylation of carbonyl compounds and imines with trifluoromethylsilane
  作者：Satoru Matsukawa、Marina Saijo

  DOI：10.1016/j.tetlet.2008.05.053

  日期：2008.7

  A highly basic phosphine, tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP), catalyzes trifluoromethylation using trifluoromethyltrimethylsilane to give the corresponding trifluoromethylated products in good to high yields, with both carbonyl compounds and imines.

  高碱性膦，三（2,4,6-三甲氧基苯基）膦（TTMPP）使用三氟甲基三甲基硅烷催化三氟甲基化，以羰基化合物和亚胺的高至高收率得到相应的三氟甲基化产物。
• Nucleophilic Trifluoromethylation of Imines under Acidic Conditions
  作者：Vitalij V. Levin、Alexander D. Dilman、Pavel A. Belyakov、Marina I. Struchkova、Vladimir A. Tartakovsky

  DOI：10.1002/ejoc.200800820

  日期：2008.11

  A general method for the trifluoromethylation of imines by using Me3SiCF3 under acidic conditions is described. The reaction is promoted by hydrofluoric acid generated in situ from KHF2 and either TFA or TfOH. A new chemoselectivity pattern was achieved, as the C=N bond was found to be more reactivate than the carbonyl group. The trifluoromethylation reaction is believed to proceed by concerted transfer

  描述了在酸性条件下使用 Me3Si 对亚胺进行三氟甲基化的一般方法。该反应由由 KHF2 和 TFA 或 TfOH 原位生成的氢氟酸促进。实现了新的化学选择性模式，因为发现 C=N 键比羰基更容易重新活化。据信，三氟甲基化反应是通过 CF3 基团从硅原子到亚胺鎓亲电试剂的协同转移而进行的。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
• Iridium-Catalyzed Reductive Alkylations of Secondary Amides
  作者：Wei Ou、Feng Han、Xiu-Ning Hu、Hang Chen、Pei-Qiang Huang

  DOI：10.1002/anie.201806747

  日期：2018.8.27

  Reported herein is the first direct, metal‐catalyzed reductive functionalization of secondary amides to give functionalized amines and heterocycles. The method is shown to have exceptionally broad scope with respect to suitable nucleophiles, which cover both hard and soft C nucleophiles as well as a P nucleophile. The reaction exhibits good chemoselectivity and tolerates several sensitive functional

  本文报道的是仲酰胺的第一个直接的，金属催化的还原性官能化反应，以生成官能化的胺和杂环。相对于合适的亲核试剂，该方法具有广泛的适用范围，既涵盖硬C亲核试剂，也包括软C亲核试剂和P亲核试剂。该反应表现出良好的化学选择性，并能耐受几个敏感的官能团。
• FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS
  申请人：Corkey Britton

  公开号：US20110021521A1

  公开（公告）日：2011-01-27

  The present invention relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein W 1 , W 2 , W 3 , R 1 , Q, X 1 , X 2 and X 3 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

  本发明涉及一类钠通道抑制剂化合物，以及它们在治疗各种疾病状态中的应用，包括心血管疾病和糖尿病。具体实施例中，该化合物的结构由下式给出：其中W1、W2、W3、R1、Q、X1、X2和X3如本文所述，以及制备和使用该化合物的方法，以及含有该化合物的药物组合物。