N-[2-(3-trifluoromethylphenyl)ethyl]morpholine | 51353-09-4

• 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: N-[2-(3-trifluoromethylphenyl)ethyl]morpholine
• 英文别名: 4-[3-(Trifluoromethyl)phenethyl]morpholine；4-[2-[3-(trifluoromethyl)phenyl]ethyl]morpholine
• CAS: 51353-09-4
• 化学式: C₁₃H₁₆F₃NO
• 分子量: 259.271
• InChiKey: DEXWRQGUDRTZSX-UHFFFAOYSA-N

物化性质

• 沸点：
  285.1±35.0 °C(Predicted)
• 密度：
  1.176±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  吗啉 、 间三氟甲基苯乙烯 在 [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II) 三氟甲磺酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 以71%的产率得到N-[2-(3-trifluoromethylphenyl)ethyl]morpholine
  参考文献：
  名称：

  钌催化乙烯基芳烃的反马尔科夫尼科夫加氢胺化

  摘要：

  报道了钌催化的乙烯基芳烃与脂肪族和苄基胺的分子间抗马尔科夫尼科夫加氢胺化反应。Ru(cod)(2-甲基烯丙基)2、1,5-双(二苯基膦基)戊烷和三氟甲磺酸的组合是测试中最有效的催化剂。在没有配体或酸的情况下进行的对照反应不形成胺。吗啉、哌啶、4-苯基哌嗪、4-BOC-哌嗪、4-哌啶酮乙烯缩酮和四氢异喹啉与苯乙烯在 5 mol % 的催化剂存在下反应生成相应的 β-苯乙胺产物，产率为 64-96% ，具有 99% 的区域选择性，并且没有烯胺副产物。无环胺如正己基甲胺和 N-苄基甲胺与苯乙烯反应的产率分别为 63% 和 50%。烷基-, 甲氧基-, 三氟甲基取代的苯乙烯在这种催化剂或含有1,1'-双（二异丙基膦基）二茂铁作为配体的相关催化剂存在下与吗啉反应，得到51-91%的产物。此外，使用均相过渡金属催化剂首次观察到α-甲基苯乙烯的加氢胺化。初步机理研究表明，该反应通过直接、不可逆、反马尔科

  DOI：

  10.1021/ja031542u

文献信息

• [EN] RUTHENIUM-CATALYZED HYDROAMINATION OF OLEFINS<br/>[FR] HYDROAMINATION D'OLEFINES CATALYSEE PAR RUTHENIUM
  申请人：UNIV YALE

  公开号：WO2005077885A1

  公开（公告）日：2005-08-25

  Applicants have unexpectedly discovered that catalysts made from a ruthenium catalyst precursor or preformed ruthenium catalysts as otherwise described in the present specification are capable of effecting the addition of a N-H bond across an olefin C=C (olefinic) bond of a substrate with a high degree of regioselectivity and enantioselectivity in high yield. These addition reactions proceed in an anti-Markovnikov or Markovnikov fashion depending upon the catalyst precursor used to generate the ruthenium catalyst which actually participates in the addition reaction. The present invention relates to methods of adding N-H bonds across an olefinic bond in a substrate, using a ruthenium catalyst precursor or catalyst I comprising a compound according to the general structure I: Formula (I) where Ru is a ruthenium atom; L1 represents one or more coordinated ancillary ligands, which may be all the same ligand or which may be a combination of different ligands, each of which may be neutral or formally charged, and each of which may be monodentate and coordinated to ruthenium through a single atom or which may be linked or chelated and bound through more than one atom; L2 represents one or more formally charged ligands which are the same or different and which are optionally susceptible to removal with a strong acid; and x is 0-6, preferably 1, y is 0-6, preferably 2 and n is 1-4, preferably 1.

  申请人意外地发现，根据本说明书描述的钌催化剂前体或预先形成的钌催化剂能够以高产率实现对底物的烯烃C=C（烯烃）键进行N-H键的加成反应，并具有很高的区域选择性和对映选择性。这些加成反应可以以反Markovnikov或Markovnikov方式进行，具体取决于用于生成实际参与加成反应的钌催化剂的催化剂前体。本发明涉及一种使用钌催化剂前体或催化剂I的方法，在底物的烯烃键上添加N-H键，催化剂I包括符合一般结构I的化合物：公式（I），其中Ru是钌原子；L1代表一个或多个配位辅助配体，可以是全部相同的配体，也可以是不同配体的组合，每个配体可以是中性的或正式带电的，每个配体可以是一齿的，并通过单个原子与钌配位，也可以是连接或螯合并通过多于一个原子结合；L2代表一个或多个正式带电的配体，可以是相同的或不同的，并且可以通过强酸去除；x为0-6，优选为1，y为0-6，优选为2，n为1-4，优选为1。
• The First Rhodium-Catalyzed Anti-Markovnikov Hydroamination: Studies on Hydroamination and Oxidative Amination of Aromatic Olefins
  作者：M. Beller、H. Trauthwein、M. Eichberger、C. Breindl、J. Herwig、T. E. Müller、O. R. Thiel

  DOI：10.1002/(sici)1521-3765(19990401)5:4<1306::aid-chem1306>3.0.co;2-4

  日期：1999.4.1

  The first transition-metal-catalyzed regiospecific anti-Markovnikov hydroamination of aromatic olefins is reported. Styrene and substituted styrenes react with secondary aliphatic amines, especially morpholine and N-arylpiperazines, in the presence of cationic rhodium complexes to give 2-aminoethenylbenzene and 2-aminoethylbenzene derivatives. Cationic [Rh(cod)(2)]+BF4- and various phosphines (1:2-mixture) were employed as in situ catalysts. According to labeling experiments, there is no evidence that the hydroamination is a consecutive hydrogenation of a previously formed enamine. Hydroamination with simple secondary amines, for example piperidine, can also be achieved by the use of a higher olefin concentration and higher reaction temperatures than those given in previously published reaction procedures. Kinetic investigations of the major reaction pathway reveal that the reaction rate of the oxidative amination and the hydroamination is dependent on the styrene and on the catalyst concentration, and independent of the amine concentration. Experiments that employed deuterium-labeled amines (N-D) provided evidence that the mechanism involves an amine-activating pathway, The substituents on the styrene, the phosphine ligand, and the solvent influence the yield of the aminations and the enamine:alkylamine ratio.
• Rhodium-Catalyzed Anti-Markovnikov Hydroamination of Vinylarenes
  作者：Masaru Utsunomiya、Ryoichi Kuwano、Motoi Kawatsura、John F. Hartwig

  DOI：10.1021/ja0293608

  日期：2003.5.1

  The transition metal-catalyzed anti-Markovnikov hydroamination of unactivated vinylarenes with a rhodium complex of DPEphos is reported. The reaction of electron-neutral or electron-rich vinylarenes with a variety of secondary amines in the presence of catalyst forms the products from anti-Markovnikov hydroamination in high yields. Reactions of morpholine, N-phenylpiperazine, N-Boc-piperazine, piperidine, 2,5-dimethylmorpholine, and perhydroisoquinoline reacted with styrene to form the amine product in 51-71% yield. Reactions of a variety of vinylarenes with morpholine generated amine as the major product. Reactions of morpholine with electron-poor vinylarenes gave lower amine:enamine ratios than reactions of electron-rich vinylarenes at the same concentration of vinylarene, but conditions were developed with lower concentrations of electron-poor vinylarene to maintain formation of the amine as the major product. Reactions of dimethylamine with vinylarenes were fast and formed amine as the major product. Mechanistic studies on the hydroamination process showed that the amine:enamine ratio was lower for reactions conducted with higher concentrations of vinylarene and that one vinylarene influences the selectivity for reaction of another. A mechanism proceeding through a metallacyclic intermediate that opens in the presence of a second vinylarene accounts for these and other mechanistic observations.
• A simple one-pot procedure for the iminium salt formation: an efficient route to β-arylethylamines
  作者：Yi-Yin Ku、Tim Grieme、Yu-Ming Pu、Ashok V. Bhatia、Steve A. King

  DOI：10.1016/j.tetlet.2005.01.027

  日期：2005.2

  A practical and highly efficient process for the preparation of beta-arylethylamines 7 was developed. Benzylic organozinc compounds 10 were reacted with the iminium salts 9 generated in situ from the amine salt 8 and para formaldehyde in one pot and in a polar and aprotic solvent, such as NMP. A variety of the beta-arylethylamines were prepared in 43-91% yields. (C) 2005 Elsevier Ltd. All rights reserved.
• Ruthenium-Catalyzed Anti-Markovnikov Hydroamination of Vinylarenes
  作者：Masaru Utsunomiya、John F. Hartwig

  DOI：10.1021/ja031542u

  日期：2004.3.1

  tetrahydroisoquinoline with styrene in the presence of 5 mol % of this catalyst formed the corresponding beta-phenethylamine products in 64-96% yield, with 99% regioselectivity, and without enamine side products. Acyclic amines such as n-hexylmethylamine and N-benzylmethylamine reacted with styrene in 63 and 50% yields, respectively. Alkyl-, methoxy-, and trifluoromethyl-substituted styrenes reacted with morpholine

  报道了钌催化的乙烯基芳烃与脂肪族和苄基胺的分子间抗马尔科夫尼科夫加氢胺化反应。Ru(cod)(2-甲基烯丙基)2、1,5-双(二苯基膦基)戊烷和三氟甲磺酸的组合是测试中最有效的催化剂。在没有配体或酸的情况下进行的对照反应不形成胺。吗啉、哌啶、4-苯基哌嗪、4-BOC-哌嗪、4-哌啶酮乙烯缩酮和四氢异喹啉与苯乙烯在 5 mol % 的催化剂存在下反应生成相应的 β-苯乙胺产物，产率为 64-96% ，具有 99% 的区域选择性，并且没有烯胺副产物。无环胺如正己基甲胺和 N-苄基甲胺与苯乙烯反应的产率分别为 63% 和 50%。烷基-, 甲氧基-, 三氟甲基取代的苯乙烯在这种催化剂或含有1,1'-双（二异丙基膦基）二茂铁作为配体的相关催化剂存在下与吗啉反应，得到51-91%的产物。此外，使用均相过渡金属催化剂首次观察到α-甲基苯乙烯的加氢胺化。初步机理研究表明，该反应通过直接、不可逆、反马尔科