Abstract: N-(1-Phenylethyl)maleimide derivatives are valuable intermediates for the synthesis of complex organic molecules, including chiral building blocks for asymmetric synthesis. Traditional synthetic methods often involve hazardous solvents, limiting their environmental compatibility and industrial applicability. The aim of this study was to develop a sustainable, efficient, and solvent-free synthetic protocol for the preparation of both chiral and achiral N-(1-phenylethyl)maleimide derivatives. This was followed by separation and analysis using chiral High-Performance Liquid Chromatography. An efficient, solvent-free methodology was employed to synthesize N-(1- phenylethyl)maleimide derivatives. The resulting chiral compounds were separated enantiomerically by chiral chromatography to obtain optically pure enantiomers. All products were characterized to confirm purity and enantiomeric excess. The solvent-free protocol enabled the synthesis of both chiral and achiral N-(1-phenylethyl)maleimide derivatives in high yields and purity. The enantiomeric resolution technique provided efficient isolation of optically pure chiral compounds. The approach demonstrated significant improvements in sustainability, operational simplicity, and scalability. This environmentally benign, solvent-free synthesis offers a practical alternative for the production and isolation of N-(1-phenylethyl)maleimide derivatives. The protocol enhances the sustainability and practicality of accessing the chiral intermediate for further synthetic applications.
Roy et al. (Fri,) studied this question.