Synthesis of substituted N-phenylmaleimides and use in a Diels–Alder reaction: a green multi-step synthesis for an undergraduate organic chemistry laboratory

Abstract

This paper describes the design and implementation of a minimally hazardous, environmentally friendly, and energy efficient sequential reaction sequence within a sophomore level Organic Chemistry lab course to efficiently synthesize N-phenylmaleimide precursors for a Diels–Alder reaction. Substituted N-phenylmaleimides are a class of very expensive precursors of considerable interest due to their biological properties and use as intermediates in synthesis. The synthesis described herein produces a substituted N-phenylmaleimide in two steps from maleic anhydride and a substituted aniline followed by its Diels–Alder reaction with 2,5-dimethylfuran. The experiment exposes students to the green chemistry principles of atom economy, use of safer chemicals, design for energy efficiency, waste reduction, and inherently safer chemistry for accident prevention and enables students to use 1H NMR spectroscopy to characterize the products.

Keywords

• Undergraduate organic chemistry
• multi-step synthesis
• maleimide
• Diels–Alder
• amine acylation