3-(3-Chloropropyl)-N-methoxyisoquinolin-1(2H)-one | 148991-90-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 3-(3-Chloropropyl)-N-methoxyisoquinolin-1(2H)-one
• 英文别名: 3-(3-Chloropropyl)-2-methoxyisoquinolin-1-one
• CAS: 148991-90-6
• 化学式: C₁₃H₁₄ClNO₂
• 分子量: 251.713
• InChiKey: VZJPQEURVNDOSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(3-Chloropropyl)-N-methoxyisoquinolin-1(2H)-one 在 titanium(III) chloride 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 1,2-Dihydro-3H,5H-pyrrolo<1,2-b>isoquinoline-5-one
  参考文献：
  名称：

  O-Methylarenehydroxamates as ortho-lithiation directing groups. Titanium(III)-mediated conversion of O-methyl hydroxamates to primary amides

  摘要：

  Reaction of O-methyl benzohydroxamates 2a-c with sec-butyllithium in the presence of TMEDA at -40-degrees-C regiospecifically generates the highly reactive N,ortho-dilithiated species (e.g. 3). These dilithio species react avidly with a wide spectrum of electrophilic reagents, including alkyl halides, giving adducts which on reduction with TiCl3 are converted into ortho-substituted primary benzamides in excellent yields. Ortho lithiation of O-methyl benzohydroxamates is thus formally equivalent to ortho lithiation of primary benzamides themselves. The utility of these synthetic operations is enhanced by the well-known facility with which the primary amide moiety can be transformed into other useful functional groups. The conversion of 0-methyl hydroxamates to primary amides is shown to be general, as exemplified by transformation of 14a-f to 15a-f.O-Methyl 2-methylbenzohydroxamate (4a) undergoes regiospecific dilithiation on nitrogen and on the methyl group when treated with sec-butyllithium at -70-degrees-C. These dilithio species react with DMF or ''Weinreb-type'' amides to give condensation products which cyclize to N-methoxyisoquinolin-1(2H)-ones under mildly acidic conditions. Removal of the N-methoxy moiety under conditions analogous to those used for O-methyl benzohydroxamate provides N-unsubstituted isoquinolin-1(2H)-ones with high overall efficiency. This process is exemplified by the synthesis of isoquinolin-1(2H)-one 9a, its 3-n-butyl congener 9b, and the tricyclic isoquinolin-1 (2H)-ones 20a and 20b from O-methyl 2-methylbenzohydroxamate (4a).

  DOI：

  10.1021/jo00066a014
• 作为产物：
  描述：

  N-甲氧基苯甲酰胺 在 四甲基乙二胺 、 仲丁基锂 作用下， 反应 0.83h， 生成 3-(3-Chloropropyl)-N-methoxyisoquinolin-1(2H)-one
  参考文献：
  名称：

  O-Methylarenehydroxamates as ortho-lithiation directing groups. Titanium(III)-mediated conversion of O-methyl hydroxamates to primary amides

  摘要：

  Reaction of O-methyl benzohydroxamates 2a-c with sec-butyllithium in the presence of TMEDA at -40-degrees-C regiospecifically generates the highly reactive N,ortho-dilithiated species (e.g. 3). These dilithio species react avidly with a wide spectrum of electrophilic reagents, including alkyl halides, giving adducts which on reduction with TiCl3 are converted into ortho-substituted primary benzamides in excellent yields. Ortho lithiation of O-methyl benzohydroxamates is thus formally equivalent to ortho lithiation of primary benzamides themselves. The utility of these synthetic operations is enhanced by the well-known facility with which the primary amide moiety can be transformed into other useful functional groups. The conversion of 0-methyl hydroxamates to primary amides is shown to be general, as exemplified by transformation of 14a-f to 15a-f.O-Methyl 2-methylbenzohydroxamate (4a) undergoes regiospecific dilithiation on nitrogen and on the methyl group when treated with sec-butyllithium at -70-degrees-C. These dilithio species react with DMF or ''Weinreb-type'' amides to give condensation products which cyclize to N-methoxyisoquinolin-1(2H)-ones under mildly acidic conditions. Removal of the N-methoxy moiety under conditions analogous to those used for O-methyl benzohydroxamate provides N-unsubstituted isoquinolin-1(2H)-ones with high overall efficiency. This process is exemplified by the synthesis of isoquinolin-1(2H)-one 9a, its 3-n-butyl congener 9b, and the tricyclic isoquinolin-1 (2H)-ones 20a and 20b from O-methyl 2-methylbenzohydroxamate (4a).

  DOI：

  10.1021/jo00066a014

文献信息

• O-Methylarenehydroxamates as ortho-lithiation directing groups. Titanium(III)-mediated conversion of O-methyl hydroxamates to primary amides
  作者：Lawrence E. Fisher、Joan M. Caroon、Jahangir、S. Russell Stabler、Scott Lundberg、Joseph M. Muchowski

  DOI：10.1021/jo00066a014

  日期：1993.7

  Reaction of O-methyl benzohydroxamates 2a-c with sec-butyllithium in the presence of TMEDA at -40-degrees-C regiospecifically generates the highly reactive N,ortho-dilithiated species (e.g. 3). These dilithio species react avidly with a wide spectrum of electrophilic reagents, including alkyl halides, giving adducts which on reduction with TiCl3 are converted into ortho-substituted primary benzamides in excellent yields. Ortho lithiation of O-methyl benzohydroxamates is thus formally equivalent to ortho lithiation of primary benzamides themselves. The utility of these synthetic operations is enhanced by the well-known facility with which the primary amide moiety can be transformed into other useful functional groups. The conversion of 0-methyl hydroxamates to primary amides is shown to be general, as exemplified by transformation of 14a-f to 15a-f.O-Methyl 2-methylbenzohydroxamate (4a) undergoes regiospecific dilithiation on nitrogen and on the methyl group when treated with sec-butyllithium at -70-degrees-C. These dilithio species react with DMF or ''Weinreb-type'' amides to give condensation products which cyclize to N-methoxyisoquinolin-1(2H)-ones under mildly acidic conditions. Removal of the N-methoxy moiety under conditions analogous to those used for O-methyl benzohydroxamate provides N-unsubstituted isoquinolin-1(2H)-ones with high overall efficiency. This process is exemplified by the synthesis of isoquinolin-1(2H)-one 9a, its 3-n-butyl congener 9b, and the tricyclic isoquinolin-1 (2H)-ones 20a and 20b from O-methyl 2-methylbenzohydroxamate (4a).