西酞普兰中间体的合成分析-synthesis and analysis of citalopram intermediate.docxVIP

西肤普兰中间体的合成研究 摘要 西献普兰是一种己经上市十多年的抗抑郁症药物，是一种 选择性的中枢活性血清素(付5 具有很好的抗事抖抑1J郁活性。副作用小。近年的研究发现，它还对治 疗痴呆症、脑血管病有疗效。 西欧普兰的合成路线很多，木论文选取当今最简单、最先 进的两条合成路线，分别研究了这两条路线重要的中间体 -5- 氨基苯肤、 5-氨基邻苯二甲默亚肢的合成。着重开发出新的合成 方法(已经分别申请了国家专利)。同时对其工业化给予了关注。 子氨基苯肤的合成采用两步合成: 1、以5-竣基苯西太为起始 原料，经过用无机氨馁化。 2、脱水剂脱水反应。经过大量的优 化实验，做到了比以往同类专利技术生产成本更低，工艺更简单， 收率更高: 85% ，含量高:98% 以上F 污染更少。 5-氨基邻苯二甲酌亚肢以 5-硝基邻苯二甲酌亚肢为原料，经 过还原而制得。对还原剂筛选 F 尤其是溶剂的选用上下了很大的 工夫。最后选用机加工的废铁粉为还原剂，二甲基亚枫为溶取的 溶剂。取得高收率，达到 900/0 、高纯度99% 、低成本、少污染 的好效果。两个中间体都已经工业化，并取得了一定的经济效益。 关键词:西肤普兰 抗抑郁药 西献普兰中间体 5-氨基苯 酥 5-氨基邻苯二甲欧亚胶 馁化 还原 溶取 Abstract Citalopram is a well know antidepressant drug that has now been on market for tens years. It is selective，centra11y acting serotonin (5-hydroxytryptamine) reuptake inhibitor，accordingly having well antidepressant activities; the side effect is very limited. The compound has further been disclosed to show effects in the treatment of dementia and cerebrovascular disorders. ηlere are many methods for manufacture of the Citalopram. Two easy and convenient method for synthesizing citalopram are selected in 也is paper .The major purpose of this paper is engaged in research about prep缸ation for two intermediates-5-cyanothphalide and 5-aminophthalimide ，using as the starting material for synthesis of citalopram ，especially searching a new methods of preparation for these intermediates (The methods of preparation for them have been applied to our country for patents.). The application of these discovers to industry has been realized. 5-cyanophthaIide is synthesized through two steps: (1)由e 5-carbonphthalide ?s used as starting material. It is aminated with concentrated ammonia spirit. (2) 5-ammonium fonnate phthalide is reacted with dehydrating agent. By the process of this invent， 5-cy缸lophthalide is obtained in a high yield (above 820/0)， cost-effective way and by a convenient process. The product possesses high qualìty，and the pollution ωenvironment is reduced. 5-aminophthalimide is prepared by re