4氯6碘喹啉的合成制药工程专业毕业论文.doc

Southwest university of science and technology 本科毕业设计（论文） 4-氯-6-碘喹啉的合成 学院名称 生命科学与工程学院 专业名称 制药工程 学生姓名 学生姓号 指导教师 二〇一X年X月 4-氯-6-碘喹啉的合成 摘要：喹啉是一种杂环芳香性有机化合物，它具有强烈臭味，易溶于热水且能与醇、醚和二硫化碳等有机溶液混溶，难溶于冷水，是一种具有吸湿性的无色液体。它是冶金、染料、聚合物以及农用化学品工业的重要中间体，也可以用作消毒剂、防腐剂以及溶剂。其中，4-氯-6-碘喹啉是一个非常有应用前景的药物合成中间体，对它的合成方法进行探索具有一定的研究价值。探索过程和结果能够为我们以后进行该方面药物的合成研究提供重要帮助。本次实验的主要内容是以米氏酸为原料，期间通过对文献报道的合成方法和反应条件进行优化和改进，最终成功地合成出4-氯-6-碘喹啉，并积累出一定的量。该合成路线分为四步，第一步是将丙二酸和丙酮在乙酸酐中缩合得到合成原料丙二酸环亚异丙酯，中文别名米氏酸，第二步由米氏酸与原甲酸三乙酯通过取代反应生成2,2-二甲基-1,3-二氧六环-5-亚甲基乙氧基-4,6-二酮，生成物进一步与对碘苯胺发生共轭加成—消除反应生成5-（4-碘苯基）氨基亚甲基丙二酸环亚异丙酯化合物A，第三步则是化合物A进一步闭环生成4-羟基-6-碘喹啉，最后一步是4-羟基-6-碘喹啉与三氯氧磷发生氯代反应合成出4-氯-6-碘喹啉。最终产物经核磁共振氢谱确认为目标结构产物，并且总产率比较理想。 关键词：药物合成中间体；米氏酸；4-氯-6-碘喹啉；氯代 Synthesis of 4-chloro-6-iodoquinoline Abstract: Quinoline , a kind of heterocyclic aromatic organic compound with strong odor , can easily dissolve in hot water , alcohol ,ether and carbon disulfide etc organic solvent,?is a colorless liquid with moisture absorption. It is an important intermediate in metallurgy, dyes , polymers and agricultural chemical industry , always used as disinfectant , preservative and solvent. Among those compounds derived by quinoline , 4 - chloro - 6 - iodoquinoline is a promising drug intermediate , there do have great value to explore it’s synthesis method, cause the exploring process and result will provide us guidance and crucial support for the further study. This study is aimed at doing some development and optimization in the synthesis method and condition of 4 - chloro - 6 - iodoquinoline based on the route reported before. Use Meldrum’s acid as raw material, after 4 steps to get a certain amount of target products. The first step is a condensation reaction of malonic acid and acetone in acetic anhydride to get Meldrum’s acid; Secondly, the Meldrum’s acid was substituted by triethyl orthoformate to get 2,2-dimethyl-1,3-dioxane-5-methylene ethoxy-4,6-diketone, then the product will take an conjugate addition-elimintion reaction with p-iodine