甲苄氧喹啉和癸氧喹啉的合成研究-材料科学与工程专业论文.docx

博士后出站报告摘 博士后出站报告 摘 要 喹啉类抗球虫药在抗球虫药物中开发较早，药效较好，至今有几种药物还添 加在饲料中，防止及治疗球虫病。本报告对喹啉类抗球虫药中药效最好的甲苄氧 喹啉和癸氧喹啉的合成进行了详细研究，得到了适宜于工业化的工艺路线。 合成甲苄氧喹啉的关键是合成其中间体3．苄氧基4．丁基苯胺，文献报道合成 3．苄氧基．4．丁基苯胺的方法是以间氨基苯酚为原料经过酰化、Fries重排、催化氢 化还原、苄基化、水解等五步反应合成其产品，总收率41．4％，该路线操作步骤 多，复杂，并且使用了比较昂贵的Pd／C催化剂。在重复文献路线的基础上，我们 设计新的合成路线：以间氨基苯酚为原料，经过酰化、Fries荤排、苄基化、还原 水解等四步反应得到目标产物，减少了操作步骤，大大降低了生产成本，总收率 达47．3％。中间体3．苄氧基4．丁基苯胺与甲氧甲叉丙二酸二甲酯经过缩合、环化 步骤合成药物甲苄氧喹啉，文献收率为6l％，我们改进了操作方法，通过对工艺 条件的优化，得到了较好的收率67．7％。 合成癸氧喹啉的关键是中间体4．癸氧基．3．乙氧基苯胺的合成，我们在参考文 献的基础上，以邻二苯酚为原料，经过O．烷基化、偶氮化、O．烷基化、催化加 氢四步反应制得。总收率为34．8％。中间体4．癸氧基．3．乙氧基苯胺和乙氧甲叉丙 二酸二乙酯经过缩合、环化步骤合成药物癸氧喹啉，我们改进了操作方法，通过 对工艺条件及参数的优化，得到了较好的收率66。1％。 关键词：抗球虫药，3-苄氧基4．丁基苯胺，甲苄氧喹啉， 4．癸氧基．3．乙氧基苯 胺，癸氧喹啉 第1页共页 博士后出站报告AB 博士后出站报告 AB STRACT The quinoline’s derivatives which arc one family of anticoccidal drugs were researched early and their effects are excellent．Up to the present,several drugs of them are still added to food to prevent or cure coccidiosis．Methylbenzoquate and decoquinate，those are two of the quinoline’s derivatives,have been used as all anticoccidal drug because of its strong effect． The key step for preparation of methylbenzoquate is synthesis of 3-bcnzyloxy-4一butylbcazenamine．In literature,the intermediate is prepared with 3-aminophenol as the raw material by a series of reaction,such鹪acylation,Fries arrangement,catalytic hydrogenation,benzylation and hydrolyzation in a yield of 41．铴．However,this type of process are inefficient and expensive due to several． complicated operation steps,high cost of Pd／C，and so on．In the new method,the process was optimized勰follows：acylation．Fries arrangement,benzylation and reduction-hydrolyzation．In the acylmion and Fried arrangement,the game solvent was used,which is more efficient for operation．In addition,the hydrazine hydrate which is cheaper substituted of Pd／C for reduction of carbonyl group．And the 3-benzyloxy-4·butylbenzenamine was obtained with a yield of 47．3％．The methylbenzoquate is prepared with 3-benzyloxy-4一butylbenzenamine and dimethyl