2-methyl-3,4-bis(4-(methoxy)phenyl)isoquinolin-1(2H)-one | 161730-00-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-methyl-3,4-bis(4-(methoxy)phenyl)isoquinolin-1(2H)-one
• 英文别名: 3,4-bis(4-methoxyphenyl)-2-methylisoquinolin-1(2H)-one；3,4-Bis(4-methoxyphenyl)-2-methyl-1(2H)-isoquinolinone；3,4-bis(4-methoxyphenyl)-2-methylisoquinolin-1-one
• CAS: 161730-00-3
• 化学式: C₂₄H₂₁NO₃
• 分子量: 371.436
• InChiKey: XJQJSDGGXUHCKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-甲基苯甲酰胺 在 正丁基锂 、 三甲基氯硅烷 、 sodium iodide 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 反应 14.17h， 生成 2-methyl-3,4-bis(4-(methoxy)phenyl)isoquinolin-1(2H)-one
  参考文献：
  名称：

  Reaction of ortho-lithiated N-methylbenzamide with 1,2-Diketones: A novel highly efficient route to N-methylisoquinolin-1-one

  摘要：

  1,2-Diketones were found to react with ortho-lithiated N-methylbenzamide to give diols 4a-g in 59-80% yields. Reaction of diols 4a-g with the system Me(3)SiCl/Nal in MeCN furnished N-methylisoquinolin-1-ones in 84-92% yields.

  DOI：

  10.1016/0040-4039(94)02293-k

文献信息

• Ruthenium-Catalyzed Oxidative Annulation by Cleavage of CH/NH Bonds
  作者：Lutz Ackermann、Alexander V. Lygin、Nora Hofmann

  DOI：10.1002/anie.201101943

  日期：2011.7.4

  Bond activation in action: Unprecedented ruthenium‐catalyzed oxidative annulations of alkynes through cleavage of CH bonds set the stage for an efficient 1(2H)‐isoquinolone synthesis with ample scope (see scheme; tAm=tert‐amyl). Mechanistic studies provided strong evidence for a rate‐limiting CH bond metalation through carboxylate assistance.

  键活化在动作：以C裂解炔烃的前所未有的钌催化氧化annulations  H键设置阶段为一个有效的1（2 ħ）-isoquinolone合成了充足的范围（参见方案;吨AM =叔戊基）。机理研究为通过羧酸盐协助限速CH键金属化提供了有力证据。
• Synthesis of isoquinolones via Rh-catalyzed C–H activation of substituted benzamides using air as the sole oxidant in water
  作者：Nitinkumar Satyadev Upadhyay、Vijaykumar H. Thorat、Ryota Sato、Pratheepkumar Annamalai、Shih-Ching Chuang、Chien-Hong Cheng

  DOI：10.1039/c7gc01221g

  日期：——

  metal-catalyzed C–H activation/annulation reactions were carried out in organic solvents using expensive oxidants such as Cu(II) and Ag(I) salts. Here, we reported a new approach for a highly regioselective synthesis of isoquinolones from N-alkyl benzamides and alkynes using an Rh(III) catalyst and inexpensive oxygen as the sole oxidant in an aqueous medium. In the reaction, water gave the highest product yield

  大多数金属催化的C–H活化/环化反应都是在有机溶剂中使用昂贵的氧化剂，例如Cu（II）和Ag（I）盐进行的。在这里，我们报道了一种新方法，可在水介质中使用Rh（III）催化剂和廉价的氧气作为唯一氧化剂，从N-烷基苯甲酰胺和炔烃高度区域选择性合成异喹诺酮。在反应中，水在所用溶剂中的产率最高。另外，在反应结束时，异喹诺酮产物直接从水溶液中沉淀出来。该方法可以应用于克级合成。Rh（III）催化的反应显示出有趣的间位与间位取代的苯甲酰胺具有选择性，并显示出不同取代的炔烃的各种区域选择性。而且，该方法可以用于制备具有异喹诺酮核心的生物活性化合物。
• Pd/C-catalyzed synthesis of N -aryl and N -alkyl isoquinolones via C H/N H activation
  作者：Zhen Shu、Yuntao Guo、Wei Li、Baiquan Wang

  DOI：10.1016/j.cattod.2017.02.005

  日期：2017.11

  Pd/C-catalyzed direct synthesis of N-aryl and N-alkyl isoquinolones was developed via the annulation reactions of benzamides and alkynes in high yields (up to 99%) through the cleavage of CH/NH bonds. The reaction was ligand-free and air was used as oxidant. High regioselectivities were found when unsymmetrical alkynes or meta-benzamides were used as substrates. The heterocyclic carboxamide substrates

  通过苯甲酰胺和炔烃的环化反应，通过C H / N H键的裂解，Pd / C催化直接合成N-芳基和N-烷基异喹诺酮。该反应不含配体，将空气用作氧化剂。当使用不对称炔烃或间苯甲酰胺作为底物时，具有较高的区域选择性。杂环羧酰胺底物，例如呋喃和噻吩衍生物，也以高收率提供了相应的产物。
• Rhodium-Catalyzed Oxidative Cycloaddition of Benzamides and Alkynes via C−H/N−H Activation
  作者：Todd K. Hyster、Tomislav Rovis

  DOI：10.1021/ja103776u

  日期：2010.8.4

  The oxidative cycloaddition of benzamides and alkynes has been developed. The reaction utilizes Rh(III) catalysts in the presence of Cu(II) oxidants, and is proposed to proceed by N-H metalation of the amide followed by ortho C-H activation. The resultant rhodacycle undergoes alkyne insertion to form isoquinolones in good yield. The reaction is tolerant of extensive substitution on the amide, alkyne, and arene, including halides, silyl ethers, and unprotected aldehydes as substituents. Unsymmetrical alkynes proceed with excellent regioselectivity, and heteroaryl carboxamides are tolerated leading to intriguing scaffolds for medicinal chemistry. A series of competition experiments shed further light on the mechanism of the transformation and reasons for selectivity.
• Reaction of ortho-lithiated N-methylbenzamide with 1,2-Diketones: A novel highly efficient route to N-methylisoquinolin-1-one
  作者：Alexander S. Kiselyov

  DOI：10.1016/0040-4039(94)02293-k

  日期：1995.1

  1,2-Diketones were found to react with ortho-lithiated N-methylbenzamide to give diols 4a-g in 59-80% yields. Reaction of diols 4a-g with the system Me(3)SiCl/Nal in MeCN furnished N-methylisoquinolin-1-ones in 84-92% yields.