5-(3,4,5-trimethoxyphenyl)-[1,3]dioxolo[4,5-g]isoquinoline-7-carboxylic acid

• 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: 5-(3,4,5-trimethoxyphenyl)-[1,3]dioxolo[4,5-g]isoquinoline-7-carboxylic acid
• 化学式: C₂₀H₁₇NO₇
• 分子量: 383.357
• InChiKey: DQXSDXPAOAQOCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  96.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  黄樟素 在 palladium on activated charcoal sodium hydroxide 、 tetrafluoroboric acid 、 乙酸酐 、 戴斯-马丁氧化剂 、 silver nitrate 、 间氯过氧苯甲酸 作用下， 以 乙醚 、 二氯甲烷 、 水 、 邻二氯苯 、 乙腈 、 萘烷 为溶剂， 反应 20.0h， 生成 5-(3,4,5-trimethoxyphenyl)-[1,3]dioxolo[4,5-g]isoquinoline-7-carboxylic acid
  参考文献：
  名称：

  Synthesis of methylenedioxy-bearing 1-aryl-3-carboxylisoquinolines using a modified Ritter reaction procedure

  摘要：

  This paper describes original approaches aimed at the preparation of electron-rich 1-aryl-3-carboxylisoquinolines. Our first attempt led to an efficient preparation of 1-hydroxyisoquinoline-3-carboxylic acid methyl ester starting from bromophthalide via a rearrangement of 2-acetylamino-2-(3-oxo-1,3-dihydroisobenzofuran-1-yl)-malonic acid dimethyl ester. However, as its eventual application to the synthesis of methylenedioxy-bearing substrates seemed rather long, a second approach involving an extension of the Ritter reaction to safrole was devised. We thus report that, under proper experimental settings, the use of 54% tetrafluoroboric acid in ether enables a Ritter reaction between safrole and 3,4,5-trimethoxybenzonitrile yielding 17% of 7-methyl-5-(3,4,5-trimethoxyphenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]isoquinoline. This acidic reagent avoids the extensive decomposition seen when using the classical Ritter reaction conditions (i.e.: concentrated sulfuric acid). Further chemical transformations of this methyl-bearing dihydroisoquinoline led to the methylenedioxy-bearing 1-aryl-3-carboxylisoquinoline. These derivatives are related to the peripheral benzodiazepine receptor ligand PK 11195 as well as falcipain-2 inhibitors and other potential antitumor agents. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.05.004

文献信息

• Synthesis of methylenedioxy-bearing 1-aryl-3-carboxylisoquinolines using a modified Ritter reaction procedure
  作者：Yves L Janin、Didier Decaudin、Claude Monneret、Marie-France Poupon

  DOI：10.1016/j.tet.2004.05.004

  日期：2004.6

  This paper describes original approaches aimed at the preparation of electron-rich 1-aryl-3-carboxylisoquinolines. Our first attempt led to an efficient preparation of 1-hydroxyisoquinoline-3-carboxylic acid methyl ester starting from bromophthalide via a rearrangement of 2-acetylamino-2-(3-oxo-1,3-dihydroisobenzofuran-1-yl)-malonic acid dimethyl ester. However, as its eventual application to the synthesis of methylenedioxy-bearing substrates seemed rather long, a second approach involving an extension of the Ritter reaction to safrole was devised. We thus report that, under proper experimental settings, the use of 54% tetrafluoroboric acid in ether enables a Ritter reaction between safrole and 3,4,5-trimethoxybenzonitrile yielding 17% of 7-methyl-5-(3,4,5-trimethoxyphenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]isoquinoline. This acidic reagent avoids the extensive decomposition seen when using the classical Ritter reaction conditions (i.e.: concentrated sulfuric acid). Further chemical transformations of this methyl-bearing dihydroisoquinoline led to the methylenedioxy-bearing 1-aryl-3-carboxylisoquinoline. These derivatives are related to the peripheral benzodiazepine receptor ligand PK 11195 as well as falcipain-2 inhibitors and other potential antitumor agents. (C) 2004 Elsevier Ltd. All rights reserved.