N-phenyl-2-(hydroxymethyl)-2-methylpropylamine | 94844-02-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-phenyl-2-(hydroxymethyl)-2-methylpropylamine
• 英文别名: 2,2-Dimethyl-3-(phenylamino)propan-1-ol；3-anilino-2,2-dimethylpropan-1-ol
• CAS: 94844-02-7
• 化学式: C₁₁H₁₇NO
• 分子量: 179.262
• InChiKey: WRFXVUPTTUCBJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-phenyl-2-(hydroxymethyl)-2-methylpropylamine 在 三乙胺 、 三氯化磷 作用下， 以 乙醚 为溶剂， 生成 2-Methoxy-3-phenyl-5,5-dimethyl-1,3,2-oxazaphosphorinane
  参考文献：
  名称：

  Conformations of saturated six-membered-ring phosphorus heterocycles related to cyclophosphamide. NMR, x-ray, and infrared studies of 2-methoxy-2-oxo-1,3,2-oxazaphosphorinane and 2-thio-1,3,2-oxazaphosphorinane

  摘要：

  DOI：

  10.1021/ja00281a037
• 作为产物：
  描述：

  二甲基丙二酸 在 lithium aluminium tetrahydride 、 氯化亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 20.5h， 生成 N-phenyl-2-(hydroxymethyl)-2-methylpropylamine
  参考文献：
  名称：

  含硅氮杂环的合成、反应性、功能化和 ADMET 性质

  摘要：

  在药物设计和开发中，含硅化合物在很大程度上被忽略了，尽管它们有可能提高药物类候选药物的效力，还可以提高其物理化学和 ADMET（吸收、分布、代谢、排泄、毒性）特性，因为它们具有独特的特性。硅的特性。这种不足在很大程度上是由于缺乏合成各种有机硅结构的通用方法。因此，已经开发出一种新的构建块策略，它不同于将硅纳入候选药物的传统方法。描述了含硅四氢喹啉和四氢异喹啉结构单元的灵活、多克级合成，以及使用优化以适应硅特性的常见反应快速构建不同官能化的含硅氮杂环的方法。此外，为了更好地阐明硅掺入的缺点和优势，在以 ADMET 为重点的生物学研究中对选定的化合物及其碳类似物提出了挑战。

  DOI：

  10.1021/jacs.8b03187

文献信息

• Insight into O₂-Promoted Base-Catalyzed<i>N</i>-Alkylation of Amines with Alcohols
  作者：Chao Wang、Changpeng Chen、Jian Han、Jingyu Zhang、Yingming Yao、Yingsheng Zhao

  DOI：10.1002/ejoc.201500086

  日期：2015.5

  efficient and practical transition-metal-free CsOH/O2 catalyst system was developed for the N-alkylation of amines with alcohols under argon. This strategy was compatible with many alcohols and exhibits excellent functional group tolerance. More significantly, the selective formation of secondary amines was achieved in excellent yields. The detailed mechanistic study gave a clear understanding of the role

  开发了一种高效实用的不含过渡金属的 CsOH/O2 催化剂体系，用于在氩气下用醇对胺进行 N-烷基化。该策略与许多醇相容，并表现出优异的官能团耐受性。更重要的是，仲胺的选择性形成以极好的收率实现。详细的机理研究清楚地了解了碱和氧在催化循环中的作用。
• X-ray and proton NMR studies of the conformational equilibria of 2-Z-3-phenyl-1,3,2-oxazaphosphorinanes. Steric and stereoelectronic influences on the unexpected axial preferences of Me2N and MeNH substituents on three-coordinate phosphorus
  作者：Yande Huang、Atta M. Arif、Wesley G. Bentrude

  DOI：10.1021/jo00075a018

  日期：1993.11

  A series of 2-Z-3-phenyl-1,3,2-oxazaphosphorinanes 7-14 (Z = MeO, (CF3)2CHO, Ph, MeNH, and Me2N) containing three-coordinate phosphorus was prepared. The conformations of the six-membered rings were investigated by H-1 and P-31 NMR spectroscopy and X-ray crystallography. The rings with substituents MeO, (CF3)2CHO, Ph, and MeNH on phosphorus can be unambiguously assigned in solution to a single chair conformation with the substituent of phosphorus axial. An X-ray crystal structure of 5,5-dimethyl-2,3-diphenyl-1,3,2-oxazaphosphorinane, 11, reveals a chair form ring with the phenyl group attached axially to phosphorus. For 13 and 14 with a Me2N substituent on phosphorus, a chair-chair equilibrium (20 reversible 21) is found in solution that features an 80-90% population (DELTAG-degrees = 0.9-1.1 kcal/mol) of the Me2N axial conformation (20). This finding contrasts sharply with the known 1 kcal/mol preference for the Me2N to be equatorial in the corresponding 2-(dimethylamino)-1,3,2-dioxaphosphorinanes. The ability of the 1,3,2-oxazaphosphorinane ring to accommodate the Me2N substituent axially is also seen in the X-ray crystal of 5,5-dimethyl-3-phenyl-2-(dimethylamino)-1,3,2-oxazaphosphorinane, 13, which features a chair conformation ring that is considerably distorted compared to that of 11, quite evidently to allow the Me2N to be in the observed axial orientation, conformation 20. It is argued that the axial orientation of the Me2N in 13 and 14 is at least partly in response to steric repulsions in the alternative chair conformation 21 between the equatorial Me2N and the phenyl substituent at N(3). This effect is in direct contrast to the repulsive interactions between the N(3)Ph and axial Me2N on phosphorus previously demonstrated for four-coordinate, 2-oxo-1,3,2-oxazaphosphorinanes. The increased bond lengths within the 1,3,2-oxazaphosphorinane ring over its 1,3,2-dioxaphosphorinane counterpart (C-N vs C-O) and increased ring flexibility, along with potential n --> sigma* stereoelectronic factors of the type operative in the anomeric effect, are also proposed as potential contributors to the preferred axial orientation of Me2N in 13 and 14. The diastereomeric molecules cis- and trans-5-tert-butyl-3-phenyl-2-(dimethylamino)-1,3,2-oxazaphosphorinane, 17, also were prepared. At thermodynamic equilibrium at room temperature, cis-17 (2-Me2N and 5-t-Bu groups cis) is favored (cis/trans = 80/20). cis-17 displays a conformational equilibrium (Scheme 1) involving a chair conformer (almost-equal-to 60%) with the t-Bu equatorial and Me2N axial, cis-17a, and a single twist or boat form with both substituents pseudoequatorial, cis-17d (almost-equal-to 40%). trans-17 exists in solution in three conformations in approximately equal populations: a chair form with both t-Bu and Me2N equatorial (trans-17a) and two boat/twist forms (trans-17b and trans-17c) with the t-Bu pseudoequatorial and the Me2N pseudoaxial. The distributions of chair and boat/twist conformations can be reasonably understood in terms of the same 1,3-syn axial and vicinal PhN-(3)/Me2N(eq) steric repulsions invoked to explain the chair-chair equilibria noted for the unsubstituted and 5,5-dimethyl-2-(dimethylamino)-3-phenyl-1,3,2-oxazaphosphorinanes 13 and 14. The free energy difference between chair and boat/twist forms evidently is very small.
• Conformations of saturated six-membered ring phosphorus heterocycles. Chair-chair equilibria for cyclophosphamide, the 5,5-dimethyl derivative, and related 1,3,2-oxazaphosphorinanes. Relative conformational energies of nitrogen mustard and other R2N groups attached to phosphorus
  作者：William N. Setzer、Alan E. Sopchik、Wesley G. Bentrude

  DOI：10.1021/ja00293a044

  日期：1985.4
• Evans, Andrew R.; Martin, Russell; Taylor, Giles A., Journal of the Chemical Society. Perkin transactions I, 1987, p. 1635 - 1640
  作者：Evans, Andrew R.、Martin, Russell、Taylor, Giles A.、Yap, C. H. Maurice

  DOI：——

  日期：——
• SETZER, W. N.;SOPCHIK, A. E.;BENTRUDE, W. G., J. AMER. CHEM. SOC., 1985, 107, N 7, 2083-2091
  作者：SETZER, W. N.、SOPCHIK, A. E.、BENTRUDE, W. G.

  DOI：——

  日期：——