A green, chemoselective, and practical approach toward N-(2-azetidinonyl) 2,5-disubstituted pyrroles

Pyrrole and 2-azetidinone are two essential heterocyclic scaffolds, which are being broadly used in medicinal chemistry and drug discovery field. A green and practical method to synthesize novel N-(2-azetidinonyl) 2,5-disubstituted pyrroles, which are comprised of both pyrrole and 2-azetidinone moieties, has been developed. The classical Paal-Knorr reaction is one of the simplest and most economical methods for the synthesis of biologically important and pharmacologically useful pyrrole derivatives. The present procedure for the synthesis of N-(2-azetidinonyl) 2,5-disubstituted pyrroles (1,2,5-trisubstituted pyrroles) has been accomplished by reacting 3-amino β-lactams and 2,5-hexanedione in the presence of bismuth nitrate pentahydrate as an ecofriendly catalyst using microwave irradiation under solvent free condition. A comparison has also been made between the efficiency of microwave-assisted condition and the classical method (stirring at room temperature). The present method is equally effective for N-polyaromatic substituted β-lactams and optically pure β-lactams with chemically sensitive functionalities. The structure and stereochemistry of the products have been confirmed by extensive spectroscopic and X-ray crystallographic analyses. The present procedure for synthesizing N-(2-azetidinonyl) 2,5-disubstituted pyrroles may find application in the development of potent pharmacologically active molecules.