3,4-bis(4-fluorophenyl)-2-methylisoquinolin-1(2H)-one

• 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: 3,4-bis(4-fluorophenyl)-2-methylisoquinolin-1(2H)-one
• 英文别名: 3,4-Bis(4-fluorophenyl)-2-methylisoquinolin-1-one
• 化学式: C₂₂H₁₅F₂NO
• 分子量: 347.364
• InChiKey: ROELLENRDUGKDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  20.3
• 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 3,4-bis(4-fluorophenyl)-2-methylisoquinolin-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。
• 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.