N-Methoxy-3-butylisoquinolin-1(2H)-one | 148991-89-3

• 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: N-Methoxy-3-butylisoquinolin-1(2H)-one
• 英文别名: 3-butyl-2-methoxyisoquinolin-1(2H)-one；3-Butyl-2-methoxyisoquinolin-1-one
• CAS: 148991-89-3
• 化学式: C₁₄H₁₇NO₂
• 分子量: 231.294
• InChiKey: YXJUWLZBCDWEHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 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：

  N-Methoxy-3-butylisoquinolin-1(2H)-one 在 titanium(III) chloride 、 air 作用下， 生成 3-n-butyl-1(2H)-isoquinolinone
  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 N-Methoxy-3-butylisoquinolin-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

• Tunable Synthesis of 3-Hydroxylisoquinolin-1,4-dione and Isoquinolin-1-one Enabled by Copper-Catalyzed Radical 6-<i>endo</i> Aza-cyclization of 2-Alkynylbenzamide
  作者：Renzhi Liu、Meng Li、Wenlin Xie、Hongwei Zhou、Yajing Zhang、Guanyinsheng Qiu

  DOI：10.1021/acs.joc.9b01643

  日期：2019.9.20

  In this work, switchable synthesis of isoquinolin-1-one and 3-hydroxylisoquinolin-1,4-dione from 2-alkynylbenzamide is reported. The transformation works well with good yields and a broad reaction scope. The synthetic switch for providing isoquinolin-1-one and 3-hydroxylisoquinolin-1,4-dione is enabled by the use of a N2 or O2 atmosphere. Mechanism studies show that the reaction proceeds in a regioselective

  在这项工作中，据报道可从2-炔基苯甲酰胺合成异喹啉-1-酮和3-羟基异喹啉-1,4-二酮。该转化效果良好，收率高，反应范围广。通过使用N 2或O 2气氛，可以提供用于提供异喹啉-1-酮和3-羟基异喹啉-1,4-二酮的合成开关。机制研究表明，经由N-二中心自由基6-区域选择性的方式进行反应内切-挖氮杂环化通路。
• Access to divergent benzo-heterocycles via a catalyst-dependent strategy in the controllable cyclization of o-alkynyl-N-methoxyl-benzamides
  作者：Dong Ding、Tao Mou、Jiahui Xue、Xuefeng Jiang

  DOI：10.1039/c7cc01861d

  日期：——

  regio-selectively controllable approach for construction of diverse benzo-heterocycles is established. A new strategy for using the ligand effect in gold catalysis to control the regioselectivity in the cyclization of o-alkynyl-N-methoxyl-benzamide is successfully achieved. Meanwhile, the chemoselectivity between nitrogen and oxygen nucleophiles is precisely switched by gold and platinum catalysts.

  建立了化学和区域选择性可控制的方法来构建各种苯并杂环。成功实现了在金催化中利用配体效应来控制邻炔基-N-甲氧基-苯甲酰胺环化反应中区域选择性的新策略。同时，氮和氧亲核试剂之间的化学选择性可通过金和铂催化剂精确切换。
• 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).