芦竹碱及其衍生物的合成研究

Study on the Synthesis of Gramine and Its Derivatives

目的:通过曼尼希法和路易斯(Lewis)酸催化法合成芦竹碱,比较两种合成方法优劣。方法:通过正交试验考察反应物料比(吲哚:乙酸)、反应时间以及反应温度对曼尼希法合成芦竹碱的产率影响;考察反应溶剂、反应时间以及催化剂对Lewis酸催化法的影响。并研究不同底物对芦竹碱衍生物的合成影响。结果:曼尼希法合成芦竹碱,55℃时,n(吲哚):n(乙酸)=1:2反应12 h最佳,产率为88.5%。Lewis酸催化法的最佳条件是以乙醇为溶剂,ZnCl2为催化剂反应120 min,产率为93.1%。结论:Lewis酸催化法合成芦竹碱优于曼尼希法。Lewis酸催化法合成芦竹碱衍生物的结果表明,参与反应胺的位阻越大,产率越低;吲哚上引入供电子基可使产率提高,吸电子基的引入则会降低产率。

Objective:To compare the advantages and disadvantages of Mannich method and Lewis acid catalysis in the application of gramine synthesis.Methods:The effects of reaction material ratio(indole:acetic acid),reaction time and reaction temperature on the yield of gramine synthesized by Mannich method,and the effects of reaction solvent,reaction time and catalyst on the yield of gramine synthesized by Lewis acid catalysis were investigated through orthogonal experiments.The effects of different substrates on the synthesis of gramine derivatives were also studied.Results:The result of Mannich method indicated that the yield could reach 88.5%when n(indole):n(acetic acid)=1:2 for 12 hours at the temperature of 55℃.The optimal conditions for Lewis acid catalysis were using ethanol as the reaction solvent and ZnCl2 as the catalyst for 120 minutes,making the yield as much as 93.1%.Conclusion:Lewis acid catalysis synthesis of gramine is superior to Mannich method.The results showed that the larger the steric hindrance of the amines involved in the reaction,the lower the reaction yield was.The introduction of electron-donating groups on indole could increase the yield of the derivatives,while on the contrary,the introduction of electron-withdrawing groups would lead to lower yield.