节点文献
抗球虫药地考喹酯的合成工艺研究
Study on the Synthesis of Decoquinate
【作者】 狄庆锋；
【作者基本信息】 华东理工大学 ， 有机化学， 2011， 硕士
【摘要】 本论文对抗球虫药地考喹酯的合成工艺进行了研究。以苯胺为原料,经重氮化、偶合、还原、缩合、成醚、关环共六步得到产物地考喹酯,总收率由文献的34.8%提高到51.6%。在重要中间体4-羟基-5-乙氧基苯胺的合成中,通过保险粉还原偶氮化合物的方法在芳香环上引进氨基,不仅三步一锅合成,而且还原产物容易分离。粗品纯度可达95%,三步收率为86%,较文献提高了26.3%。在目标产物地考喹酯的合成中,中间体可不经提纯,直接进行反应。缩合反应在无溶剂条件下进行；癸烷基化反应通过加水催化,严格控制反应体系的含水量在2%-5%,不仅可以加快反应速率,而且提高了转化率,避免了昂贵催化剂NaI或KI的使用。三步反应总产率为60%。本合成路线中间体均不经提纯,且氨基的引入中避免了贵金属的加氢还原,减少了中间体的后处理以及有机溶剂的使用,是一条适合大规模生产地考喹酯的新合成工艺路线。
【Abstract】 The thesis focused on the synthesis of anti-coccidial drug Decoquinate.Decoquinate was synthesized with aniline as starting materials by steps of diazotization, coupling, reduction, condensation, substitution and cyclization. The total yield was improved from the reported 34.8% to 51.6%.3-Ethoxyl-4-hydroxyl-l-nitrobenzene was prepared through diazotization of anilliane, coupling with o-ethoxyl phenol and followed by the reduction of azo compounds with sodium hyposulfite in one pot in overall yield of 86% and 95% HPLC purity.Decoquinate was obtained from 3-ethoxyl-4-hydroxyl-l-nitrobenzene through condensation, etherization and cyclization without purification of the intermediates in overall yield of 60%. The condensation was carried out in absence of solvents and the etherization was realized in the presecence of 2-5% water which accelerated the reaction and increased the conversion and avoided the usage of precious catalyst of NaI or KI.The synthesis of decoquinate was suitable for mass production without purification of the intermediates, the metal reduction and the post-processure of intermediates and organic solvents.