4-methoxy-N-(3-methylbutan-2-yl)aniline | 293743-26-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-methoxy-N-(3-methylbutan-2-yl)aniline
• 英文别名: Benzenamine, N-(1,2-dimethylpropyl)-4-methoxy-
• CAS: 293743-26-7
• 化学式: C₁₂H₁₉NO
• mdl: MFCD11147343
• 分子量: 193.289
• InChiKey: DCTBFCRADOZWBX-UHFFFAOYSA-N

物化性质

• 沸点：
  290.3±23.0 °C(Predicted)
• 密度：
  0.968±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-methoxy-N-(3-methylbutan-2-yl)aniline 在 劳森试剂 、 吡啶 、 potassium carbonate 作用下， 以 六甲基磷酰三胺 、 甲苯 为溶剂， 生成 N-(1,2-Dimethyl-propyl)-4-methoxy-N-(4-methoxy-phenyl)-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-(p-methoxyphenyl)-1,2-dimethylpropylidenamine 在 C₄₄H₅₃N₅OPRu⁽¹⁺⁾*Cl^(1-) 、 potassium tert-butylate 、 氢气 作用下， 以 2-甲基四氢呋喃 为溶剂， 70.0 ℃ 、500.01 kPa 条件下， 反应 6.0h， 生成 4-methoxy-N-(3-methylbutan-2-yl)aniline
  参考文献：
  名称：

  含卢替丁衍生的钳式CNC配体的钌（II）配合物：CN键的合成，结构和催化加氢

  摘要：

  通过与相应的银卡宾衍生物进行重金属化制备了一系列含卢剔啶衍生的钳式CNC配体的Ru络合物。这些衍生物的表征显示了CN配体的mer和fac配位，这取决于N-杂环卡宾片段的翼尖。在存在t BuOK的情况下，Ru-CNC络合物在一系列亚胺的氢化中具有活性。另外，这些络合物催化菲啶啶的可逆氢化。详细的NMR光谱研究表明，CNC配体具有去质子化能力，并参与了配体辅助的二氢活化。更有趣的是，Ru-CNC络合物5 e（BF4）能够向金属-配体骨架中添加醛亚胺以产生酰胺基络合物。最后，通过DFT计算对亚胺的氢化机理进行了研究。计算的机理包括在钳形配体或第二个配位的H 2分子的协助下，外球面逐步将氢转移至CN键。

  DOI：

  10.1002/chem.201406040

文献信息

• A Versatile Catalyst for Reductive Amination by Transfer Hydrogenation
  作者：Chao Wang、Alan Pettman、John Basca、Jianliang Xiao

  DOI：10.1002/anie.201002944

  日期：——

  An iridium catalyst enables the reductive amination of carbonyl groups with unprecedented substrate scope, selectivity, and activity using formic acid as the hydrogen source (see scheme). The catalyst system provides significant improvement over commonly used boron hydrides.

  铱催化剂使用甲酸作为氢源，可实现羰基的还原胺化，具有前所未有的底物范围，选择性和活性。与常用的氢化硼相比，该催化剂体系有明显的改进。
• Hydrogen Bond Catalyzed Direct Reductive Amination of Ketones
  作者：Dirk Menche、Jorma Hassfeld、Jun Li、Gerd Menche、Antje Ritter、Sven Rudolph

  DOI：10.1021/ol053001a

  日期：2006.2.1

  [reaction: see text] A novel, biomimetic concept for the direct reductive amination of ketones is described that relies on selective imine activation by hydrogen bond formation. The mild, acid- and metal-free process requires only catalytic amounts of thiourea as hydrogen bond donor and utilizes the Hantzsch ester for transfer hydrogenation. The method allows the efficient synthesis of structurally

  [反应：见正文]描述了一种新颖的仿生概念，用于酮的直接还原胺化，该概念依赖于通过氢键形成的选择性亚胺活化。温和，无酸和无金属的过程仅需要催化量的硫脲作为氢键供体，并利用汉茨酯进行转移氢化。该方法允许有效合成结构上不同的胺。
• Iron-catalyzed amination of alcohols assisted by Lewis acid
  作者：Hui-Jie Pan、Teng Wei Ng、Yu Zhao

  DOI：10.1039/c5cc03399c

  日期：——

  An efficient Lewis acid-assisted, iron-catalyzed amination of alcohols using borrowing hydrogen methodology was developed. In particular, silver fluoride was identified to be a highly effective additive to overcome the low...

  开发了一种有效的路易斯酸辅助铁催化胺化的方法，采用借用氢方法。特别是，氟化银被认为是克服低汞排放的高效添加剂。
• An Easy and General Iron-catalyzed Reductive Amination of Aldehydes and Ketones with Anilines
  作者：Steffen Fleischer、Shaolin Zhou、Kathrin Junge、Matthias Beller

  DOI：10.1002/asia.201100462

  日期：2011.9.5

  A will of iron: An iron‐catalyzed reductive amination of aldehydes and ketones with anilines using molecular hydrogen is presented. Under mild conditions, high yields for a broad range of aryl, alkyl, and heterocyclic ketones as well as aldehydes are achieved.

  铁的遗嘱：介绍了使用分子氢对苯胺类化合物进行铁催化的醛和酮的还原胺化反应。在温和的条件下，可以实现多种芳基，烷基和杂环酮以及醛的高收率。
• Development of New Hydrogenations of Imines and Benign Reductive Hydroaminations: Zinc Triflate as a Catalyst
  作者：Svenja Werkmeister、Steffen Fleischer、Shaolin Zhou、Kathrin Junge、Matthias Beller

  DOI：10.1002/cssc.201100633

  日期：2012.4

  The hydrogenation of imines to amines in the presence of catalytic amounts of zinc triflate has been demonstrated for the first time. In addition, an efficient procedure for the reductive hydroamination of alkynes to amines is presented using zinc triflate as a catalyst precursor. In both protocols a variety of different functional groups are tolerated, and the reactions proceed smoothly in high yields

  首次证明了在催化量的三氟甲磺酸锌存在下将亚胺氢化为胺。另外，提出了使用三氟甲磺酸锌作为催化剂前体的炔烃还原性加氢胺化成胺的有效方法。在这两种方案中，都可以耐受各种不同的官能团，并且反应可以高收率顺利进行。