氯化两面针碱合成方法的改进
收稿日期: 2014-12-20
修回日期: 2015-01-28
网络出版日期: 2015-02-10
基金资助
国家自然科学基金(81230090)、上海市重点学科建设(No. B906)资助项目.
Process Improvement on the Synthesis of Nitidine Chloride
Received date: 2014-12-20
Revised date: 2015-01-28
Online published: 2015-02-10
Supported by
Project supported by the NSFC (No. 81230090), the Shanghai Leading Academic Discipline Project (No. B906).
以6-溴-3,4-二甲氧基苯甲醛和6,7-亚甲二氧基-1-萘胺为起始原料, 经还原胺化、分子内Heck偶联、氧化芳构化、甲基化以及离子交换等五步反应, 完成了氯化两面针碱的合成, 并对关键步骤分子内Heck偶联反应条件进行了探索, 结果表明该偶联反应在醋酸钯、三(邻甲苯基)膦和N,N'-二甲基甲酰胺体系中反应效果最佳, 收率显著提高. 该优化条件为结构类似苯并[c]菲啶类生物碱母核结构的构建提供了借鉴.
关键词： 氯化两面针碱; 分子内Heck偶联反应; 合成改进
许旭升 , 刘志千 , 邵文浩 , 叶霁 , 孙青龑 , 何薇薇 , 张卫东 . 氯化两面针碱合成方法的改进[J]. 有机化学, 2015 , 35(6) : 1353 -1356 . DOI: 10.6023/cjoc201412036
Nitidine chloride was synthesized via reductive amination, intramolecular Heck coupling reaction, aromatization, methlyation and ion exchange, using 6-bromine-3,4-dimethoxybenzaldehyde and 6,7-methylenedioy-1-naphthylamine as starting material. The key intramolecular Heck coupling reaction was optimized, and acetic acid palladium(II) [Pd(OAc)2], tris(2-methylphenyl)phosphine [P(o-tol)3] and N,N-dimethylformamide (DMF) system was confirmed as the most efficient conditions. The total yield was increased significantly, and the optimal conditions may also be applied to the synthesis of other benzo[c]phenanthridine alkaloid.
Key words： nitidine chloride; intramolecular Heck reaction; synthesis
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