摘 要: 近年来，国内外医学界将卡托普利与氢氯噻唑或吲达帕胺等降血压老药组成复方制剂治疗原发性高血压病取得良好效果，这些新的用法将大大拓展卡托普利的用量．由于卡托普利具有广泛的临床应用以及巨大的经济效益等特点，除了各种类型的高血压有明显的降压作用，还具有疗效高，副作用小，具有用量少的优点，其合成方法的研究引起了学者们的关注，该合成路线的设计尝试，对工艺条件进行了研究。碱性离子液体［bmim］OH能有效地增进硫代乙酸和甲基丙烯酸乙烯酯的迈克尔加成反应，反应在室温条件下进行，在30 min内可以取得定量收益率的2-甲基-3-乙酰硫基丙酸乙烯酯． 以甲基丙烯酸乙烯酯为起始原料，提出了一种合成卡托普利的新方法．57683

毕业论文关键词：卡托普利，工艺过程，合成路线

Abstract: At home and abroad in recent years, the medical profession to captopril and hydrogen chloride thiazole and indapamide fall blood pressure of old medicine compound preparation for treating primary hypertension achieve good effect, the new usage will greatly expand the amount of captopril. Because captopril has wide clinical application and the characteristics of huge economic benefits, in addition to the various types of high blood pressure have obvious antihypertensive effect, but also has high curative effect, side effect is small, possesses the advantages of less dosage, the study of its synthetic methods has caused the attention of scholars, the synthetic route design, studied the process conditions. A novel protocol for the Michael addition of  thiolacetic acid to methacrylic acid vinyl ester was developed using a basic ionic liquid［bmim］OH as catalyst and solvent,the reaction was carried out at room temperature and could obtain good yields in 30 min. A new synthesis of active pharmaceutical ingredients named captopril,the was achieved by Michael addition and N-acylation,in high purity from methacrylic acid vinyl ester.

KeyWords: captopril, craft process, synthetic rout 

目 录

1  绪论 3

1.1卡托普利的性质及用途 3

1.2卡托普利合成及生产情况 3

1.2.1先制备酰胺碳-氮键,后完成 2S与2R构型化合物分离的途径 4

1.2.2先形成2S 构型的侧链,后形成酰胺碳-氮键的途径 6

1.3重结晶与萃取技术 8

1.3.1重结晶技术 8

1.3.2萃取技术 8

1.4碱性离子液体研究进展 8

1.5本文研究的目的与内容 8

2  实验部分 8

2.1实验仪器和试剂 9

2.2实验原理 9

2.3卡托普利合成方法与内容 9

2.3.1 2-甲基-3-乙酰硫基丙酸乙烯酯的制备与表征 9

2.3.2 1-(3-乙酰巯基-2-甲基丙酰基)吡咯-2-羧酸的制备与表征 10

2.3.3 1-(3-巯基-2-甲基丙酰基)吡咯-2-羧酸的制备与表征 10

2.4研究产品表征数据 11

3  分析与讨论 13

小结 15

参考文献 16

致谢 17

1 绪论