Novel Synthesis Of Isoindoline Carboxylic Ester Derivatives

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.