摘 要

5-溴苯酞，属于带有芳香结构的五元杂环类化合物。是西酞普兰的药物中间体，由于在同类药物中相对选择性最高，很少引起药物的相互作用，产生的不良反应较少。本次对5-溴苯酞的合成工艺研究的目的是为了能够找到一种低成本、操作条件温和、环境负荷小、适合工业化工生产的药物合成方法。用邻苯二甲酰亚胺作为为原料的，经过硝酸硝化，铁粉还原，以及锌粉碱液的还原开环，酸化闭环，最后重氮化-溴化合成了5-溴苯酞，总收率为20%。本文主要探讨了硝化反应的反应条件以及还原开环反应中温度控制，酸碱度控制对反应的影响。结果表明，邻苯二甲酰亚胺与硝酸的投料比为3:1时反应效果明显，而对于还原反应中铁粉以及铵盐的使用则是用浓盐酸与氯化铵为好，碱液锌粉还原中对温度的要求较高，重氮化-溴化中加料方式采用溴化亚铜的氢溴酸溶液分批加入重氮盐中为好。通过本次实验研究对以往的方法进行了部分的改进和优化，使得反应的效果更加理想。

关键词：邻苯二甲酰亚胺；5-溴苯酞；硝化；重氮化-溴化

Abstract

5-bromophthalide, aka 5- bromine isobenzofuran ketone - -l (3H), is a five membered heterocyclic aromatic structure. Mainly used in the synthesis of antidepressant citalopram. Citalopram as a new generation of antidepressant drugs, due to the relatively selective in drugs of similar highest rarely cause significant drug drug interactions, less adverse reaction. The synthesis route of 5- 5-bromophthalide due to low cost, mild operating condition, more and more attention. The of 5-bromophthalide synthesis research is designed to find a low cost, mild operation conditions, environmental load is small, suitable for industrialized production of synthetic method. With phthalimide as starting material, through nitration, reduction with iron powder, and zinc alkaline reduction ring opening, acidification closed-loop, finally nitride - bromination of 5-bromophthalide was synthesized, total yield is 20%. This paper mainly discusses the reaction conditions of nitration reaction and the effect of temperature control in the ring opening reaction, and the effect of pH control on the reaction. The results showed that phthalic dimethyl imide and nitric acid feed ratio 3:1 reaction effect is obvious, and for the reduction reaction of iron powder and ammonium use is with concentrated hydrochloric acid and ammonium chloride as well, alkaline zinc powder reduction of temperature requirements higher, diazotization, bromination in feeding mode using bromine of cuprous hydrobromic acid solution batch addition of the diazonium salt as well. Through this experimental study, the former method is improved and optimized, which makes the effect more ideal.

Keywords: phthalate two phthalimide；5-bromophthalide； nitrification;；diazo – bromide.

目录

摘要 I

Abstract II

第一章 绪论 1

1.1 5-溴苯酞简介 1

1. 1. 1 5-溴苯酞的性质及用途 1

1.2 5-溴苯酞的合成方法 1

1.2 1 4-溴苯酐还原法 1

1.2 2邻苯二甲酸酐法 2

1.2 3 邻二甲苯法 2

1.2 4 4-溴-2-甲基苯甲酸法 3

1.3 本论文研究内容 4

1.3 1 邻苯二甲酰亚胺法 4

1.3 2 4-硝基邻苯二甲酰亚胺的合成 4

1.3 3 4-氨基邻苯二甲酰亚胺的合成 5

1.3 4 5-氨基苯酞的合成 5

1.3 5 5-溴苯酞的合成 6

1.4 实验试剂和仪器 6

1.4.1 实验试剂 6

1.4.2 实验仪器 7

第二章 4-硝基邻苯二甲酰亚胺的合成 9

2.1 实验步骤 9

2.2 实验分析 10

2.3 实验小结 11

第三章 4-氨基邻苯二甲酰亚胺的合成 13

3.1 实验步骤 13

3.2实验分析 13

3.3 实验小结 15

第四章 5-氨基苯酞的合成 17

4.1 实验步骤 17

4.2 实验分析 17

4.3 实验小结 18

第五章 5-溴苯酞的合成 20

5.1 实验步骤 20

5.2 实验分析 20

5.3 实验小结 21

第六章 结论 23

致谢 24

参考文献 25

第一章 绪论

1.1 5-溴苯酞简介

1. 1. 1 5-溴苯酞的性质及用途

5-溴苯酞 英文名: 5-bromophthalide

结构式：

分子式：