吲哚与含氟乙酸的Friedel-Crafts氟乙酰化反应合成氟乙酰基吲哚的研究

发布时间：2018-10-24 14:28

【摘要】：由于含氟取代吲哚这一结构单元在生物活性化合物和药物合成中的重要性,在吲哚环上引入氟原子或含氟官能团引起了化学家们越来越多的关注。过去的几年里,在含氟取代吲哚的合成方法上也取得了重大进展。但是,这其中的一些方法仍然存在着缺陷,例如反应条件苛刻、使用昂贵的含氟试剂、有毒和贵重的金属催化剂以及反应选择性差。因此,发展简单、高效的从便宜的氟试剂来合成含氟取代吲哚的方法仍然是极其需要的。考虑到环境和经济的问题,使用羧酸作为绿色酰化试剂的Friedel-Crafts酰化反应是一个很好的合成策略,因为在这个酰化过程中,水是唯一的副产物,而且羧酸还具有稳定性好、经济易得和具有比酰氯和酸酐更容易操作处理的优点。因此,研究和发展实用的羧酸作为酰化试剂的Friedel-Crafts酰化反应越来越受到化学家们的青睐。3-氟乙酰基吲哚表现出了非常好的生物活性,并且也是重要的药物合成中间体。尽管已有许多三氟甲基吲哚的合成方法,但是氟乙酰基吲哚的合成方法却相对较少。因此,研究合成各种各样的3-氟乙酰基吲哚的新方法是非常有意义和价值的。本论文就以吲哚作为研究对象,以氟取代乙酸作为氟乙酰化试剂,对吲哚的Friedel-Crafts氟乙酰化反应展开了一系列研究。首先,我们综述了近年来含氟取代吲哚的合成方法和羧酸作为酰化试剂在Friedel-Crafts酰化反应中的进展。其次,分别使用三氟乙酸、氯二氟乙酸、溴二氟乙酸和二氟乙酸作为氟乙酰化试剂对吲哚的Friedel-Crafts氟乙酰化反应进行了研究。结果表明,这个新方法为合成多种多样的3-氟乙酰基吲哚提供了一条实用的途径。
[Abstract]:Due to the importance of fluorine substituted indole as a structural unit in the synthesis of bioactive compounds and drugs, the introduction of fluorine atoms or fluorine-containing functional groups into the indole ring has attracted more and more attention of chemists. Significant progress has also been made in the past few years in the synthesis of fluorinated substituted indole. However, some of these methods still have defects, such as harsh reaction conditions, expensive fluorine reagents, toxic and valuable metal catalysts, and poor selectivity. Therefore, the development of a simple and efficient method for the synthesis of fluorinated substituted indole from cheap fluorine reagents is still extremely needed. Friedel-Crafts acylation using carboxylic acids as green acylation reagents is a good synthesis strategy, given that water is the only by-product of the acylation process and carboxylic acids are stable, Economical and easy-to-get and have the advantage of easier operation than acyl chloride and anhydride. Therefore, the research and development of practical carboxylic acid as acylation reagent Friedel-Crafts acylation reaction has been more and more favored by chemists. 3-fluoroacetyl indole shows very good biological activity and is also an important intermediate for drug synthesis. Although there are many methods for the synthesis of trifluoromethyl indole, there are relatively few methods for the synthesis of fluoroacetyl indole. Therefore, it is of great significance and value to study and synthesize various new methods of 3-fluoroacetyl indole. In this paper, Friedel-Crafts fluoroacetylation of indole was studied with fluorinated acetic acid as fluoroacetylation reagent and indole as research object. Firstly, we reviewed the synthesis methods of fluorinated indoles and the progress of carboxylic acids as acylation reagents in Friedel-Crafts acylation reactions in recent years. Secondly, Friedel-Crafts fluoroacetylation of indole was studied using trifluoroacetic acid, chlorodifluoroacetic acid, bromodifluoroacetic acid and difluoroacetic acid as fluoroacetylation reagents. The results show that this new method provides a practical approach for the synthesis of 3-fluoroacetyl indole.
【学位授予单位】：西北大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O621.251

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