N-cyanomethyl-N-[3-phenyl-2-propyn-1-yl]-p-toluenesulfonamide | 1307725-89-8

• 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-cyanomethyl-N-[3-phenyl-2-propyn-1-yl]-p-toluenesulfonamide
• 英文别名: N-(cyanomethyl)-N-(3-phenylprop-2-yn-1yl)-4-methylbenzenesulfonamide；N-(cyanomethyl)-4-methyl-N-(3-phenylprop-2-ynyl)benzenesulfonamide
• CAS: 1307725-89-8
• 化学式: C₁₈H₁₆N₂O₂S
• 分子量: 324.403
• InChiKey: SMFRWSSWYIWXPS-UHFFFAOYSA-N

物化性质

• 熔点：
  97-99 °C
• 沸点：
  517.2±60.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  69.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-cyanomethyl-N-[3-phenyl-2-propyn-1-yl]-p-toluenesulfonamide 在 hafnium tetrakis(trifluoromethanesulfonate) 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 ethyl 3-oxo-4-[N-(3-phenylprop-2-yn-1-yl)-N-(p-toluenesulfonyl)amino]butanoate
  参考文献：
  名称：

  Synthesis of Azepines via a [6 + 1] Annulation of Ynenitriles with Reformatsky Reagents

  摘要：

  A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent beta-endo cydization to afford the beta-2,5-dihydropyrrolyl alpha,beta-unsaturated esters 5aa-5fc, which exhibit anticancer activity.

  DOI：

  10.1021/acs.joc.5b01397
• 作为产物：
  描述：

  3-苯基-2-丙炔-1-醇 、 N-氰甲基-4-甲基苯磺酰胺 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以82%的产率得到N-cyanomethyl-N-[3-phenyl-2-propyn-1-yl]-p-toluenesulfonamide
  参考文献：
  名称：

  Synthesis of Azepines via a [6 + 1] Annulation of Ynenitriles with Reformatsky Reagents

  摘要：

  A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent beta-endo cydization to afford the beta-2,5-dihydropyrrolyl alpha,beta-unsaturated esters 5aa-5fc, which exhibit anticancer activity.

  DOI：

  10.1021/acs.joc.5b01397

文献信息

• Nickel-Catalyzed [2+2+2] Cycloaddition of Alkyne-Nitriles with Alkynes Assisted by Lewis Acids: Efficient Synthesis of Fused Pyridines
  作者：Xu You、Xin Xie、Gaonan Wang、Meijun Xiong、Renhong Sun、Haoyi Chen、Yuanhong Liu

  DOI：10.1002/chem.201603829

  日期：2016.11.14

  A Ni/BPh3 catalyzed [2+2+2] cycloaddition of alkyne‐nitriles with alkynes has been developed, which provides an efficient route to fused pyridines under mild reaction conditions. Mechanistic studies indicate that an azanickelacycle via heterocoupling of an alkyne with a nitrile moiety is possibly formed as a key reaction intermediate. The Lewis acid catalyst is crucial to the successful transformation

  已开发出Ni / BPh 3催化炔烃与炔烃的[2 + 2 + 2]环加成反应，这为在温和的反应条件下合成熔融吡啶提供了一条有效途径。机理研究表明，可能通过炔烃与腈部分的异质偶联形成氮杂氮杂环作为关键反应中间体。路易斯酸催化剂对于成功的转化至关重要，这被认为可以促进氧化环化过程。
• Reductive Aza-Pauson-Khand Reaction of Nitriles
  作者：Hong-Gui Huang、Yu-Qing Zheng、Dayou Zhong、Jiang-Lian Deng、Wen-Bo Liu

  DOI：10.1021/jacs.3c01656

  日期：2023.5.17

  γ-Lactams are valuable heterocycles in synthetic chemistry and drug development. Here, we report a reductive aza-Pauson-Khand reaction (aza-PKR) of an alkyne, a nitrile, and Co2(CO)8. A wide array of bicyclic α,β-unsaturated γ-lactams containing two adjacent stereocenters, including an all-carbon quaternary center, from alkyne-tethered malononitriles are efficiently accessed in high diastereoselectivity

  γ-内酰胺是合成化学和药物开发中有价值的杂环化合物。在这里，我们报告了炔烃、腈和 Co 2 (CO) 8的还原氮杂-Pauson-Khand 反应 (aza-PKR) 。大量双环 α,β-不饱和 γ-内酰胺包含两个相邻的立体中心，包括一个全碳季中心，来自炔烃束缚的丙二腈以高非对映选择性有效地获得。通过实验和 DFT 计算进行的初步机理研究表明，该反应经历了氮杂 PKR 过程，然后是原位还原。由水原位生成的还原剂也为使用 D 2将氘并入内酰胺的 γ 位提供了实用工具O 作为氘源。这项研究代表了一种新的 [2 + 2 + 1] 环加成模式，可以在氮杂杂环合成中直接使用腈。
• Iron-Catalyzed Cycloaddition of Alkynenitriles and Alkynes
  作者：Brendan R. D’Souza、Timothy K. Lane、Janis Louie

  DOI：10.1021/ol2009939

  日期：2011.6.3

  The combination of Fe(OAc)(2) and an electron-donating, sterically hindered pyridyl bisimine ligand catalyzes the cycloaddition of alkynenitriles and alkynes. A variety of substituted pyridines were obtained in good yields.
• Synthesis of β-Dihydropyrrolyl and β-Pyrrolyl Acrylates and Their Antiproliferative Activity against HCT-116 and HL-60 Cells
  作者：Noriyuki Hatae、Teruki Yoshimura、Yoko Sakai、Kohei Yorozu、Chiaki Okada、Mitsuhiro Yoshimatsu

  DOI：10.3987/com-16-s(s)20

  日期：——

  The alpha,beta-unsaturated carbonyl derivatives have been reported as bioactive substances, in particular acting as antiproliferative and antifungal agents. In this study, beta-dihydropyrroly1 and beta-pyrroly1 acrylates were synthesized by copper-mediated 5-endo cyclization of isolable Blaise-type beta-enamino esters and were assessed for antiproliferative activity against HCT-116 and HL-60 cells. Some beta-dihydropyrroles and beta-pyrroles showed such activities, which were found to be due to different mechanisms: the beta-dihydropyrroles act as cytotoxic agents, whereas the beta-pyrroles act as cell cycle inhibitors.
• Synthesis of Azepines via a [6 + 1] Annulation of Ynenitriles with Reformatsky Reagents
  作者：Mitsuhiro Yoshimatsu、Miki Tanaka、Yu Fujimura、Yukiteru Ito、Yusuke Goto、Yuka Kobayashi、Hiroaki Wasada、Noriyuki Hatae、Genzoh Tanabe、Osamu Muraoka

  DOI：10.1021/acs.joc.5b01397

  日期：2015.10.2

  A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent beta-endo cydization to afford the beta-2,5-dihydropyrrolyl alpha,beta-unsaturated esters 5aa-5fc, which exhibit anticancer activity.