【作者】 马辉；

【导师】 赵康；

【作者基本信息】 天津大学 ， 药物化学， 2010， 硕士

【摘要】 异吲哚啉羧酸酯衍生物含有异吲哚啉结构单元,可看作是一类特殊的氨基酸,作为许多天然产物和药物的活性结构单元,在医药和化工领域具有重要的研究价值和应用前景。因此,合成一系列异吲哚啉羧酸酯衍生物,并进行骨架结构修饰对于合成具有更高生物活性的中间体,丰富杂环化合物均具有重要的意义。在过去的几十年中,绿色化学已逐步发展成为一门重要的学科分支,得到人们的普遍重视。绿色化学原则的研究和应用促使清洁和良性的化学过程得到快速发展。其中“安全溶剂”和“设计能源效率“成为科学家考虑的两个关键原则。运用微波替代能源,微波辅助合成化学反应以及用水作为反应溶剂的化学反应已成为越来越受欢迎和关注的科学技术。本文提供了一种合成异吲哚啉羧酸酯衍生物的有效方法。以不同取代基的苯甲醛或甲苯为起始原料,经过多步反应(六、七步)合成2-溴-2-(2-溴甲基芳基)乙酸酯,再与烷基胺、芳胺、酰胺通过N-杂环化反应制备得到。本文应用此方法合成了一系列异吲哚啉羧酸酯衍生物,化合物的结构得到了核磁氢谱、质谱的表征。该反应路线所涉及操作简便,原料廉价易得,对生态环境友好,产率较高,具有一定的适用性和应用价值。本文将传统方式与微波辅助方式合成异吲哚啉羧酸酯衍生物进行了比对。重点研究了N-杂环化反应条件:考察了碱的选择、配料比、反应温度、反应时间、溶剂等因素对反应的影响。结果得出在不加入碱的情况下,以1:1(摩尔比)原料配比,用水作为反应溶剂,在功率为700 W的微波辐射下加热至140℃,反应40 min,这一绿色最佳反应条件。更多还原

【Abstract】 The isoindoline carboxylic ester derivatives were known subunits in many natural products and pharmaceuticals. Their roles in drug design and chemical industry can not be overstated. Synthesis and modification of their structure is very important for the development of heterocyclic compounds.Within the past decade, green chemistry has attained the status of a major scientific discipline. The investigation and application of green chemistry principles has led to the development of cleaner and more benign chemical processes. The“safer solvents”and“design for energy efficiency”can be considered two key principles. The use of alternative energy microwave, microwave-assisted synthesis and water as solvent in chemical reactions has become increasingly popular and concerns of science and technology.An efficient method to synthesize and modify the isoindoline carboxylic ester derivatives was developed and described. The target molecular could be prepared from a variety of amines and the 2-bromo-2-(2-(bromomethyl) aryl)acetate derivatives via N-heterocyclization, which could be synthesized by aldehydes with different substituents or functionalized methylbenzenes through six or seven steps. A series of isoindoline carboxylic ester derivatives were synthesized using this method and their structures were chracterized by 1H-NMR spectra and LRMS.The reaction conditions of heterocyclization, such as types of media and base, ratio of starting materials and temperature, were investigated. The optimum reaction conditions was 1:1 of starting material ratio (molar ratio) using water as solvent under microwave irradiation ( 700 W ) at 140℃for 40 min in the absence of base. This is a green synthetic route.更多还原