Sustainable Synthesis of N-Alkyl-Pyrrolecarboxylic and Pyrrolepyrazinones Derivatives from Biosourced 3-Hydroxy-2-pyrones and Amines

Abstract

Pyrroles are important compounds present in biological systems, used for drug synthesis and in material chemistry. A typical strategy for the pyrrolic ring formation is centered on the Paal–Knorr reaction, where 1,4-dicarbonyl compounds react with amines giving N-substituted pyrrole derivatives. Often, the main problem of this approach is the availability of the appropriate carbonyl compounds. Here, we report a sustainable synthesis of N-substituted pyrrole carboxylic acid derivatives by the reaction of primary amines and 3-hydroxy-2-pyrones. These last compounds can easily be prepared using renewable sources and show the property to be masked 1,4-dicarbonyl compounds that are able to react efficiently with amines to form substituted pyrrolic rings. The reactions can be performed under sustainable conditions without solvents at 50–75 °C or in basic water–methanol solutions at room temperature, obtaining symmetric and asymmetric pyrroles from good to high yields. Moreover, dihydropyrrolepyrazinone derivatives can easily be prepared in high yields by the reaction of 3-hydroxy-2-pyrones and ethylenediamine.