l-Proline nitrate: a recyclable and green catalyst for the synthesis of highly functionalized piperidines

Abstract

The synthesis of highly functionalized piperidines has been strategically accessed via organo-catalytic three components (in situ five components) reaction of an amine, aldehyde and 1,3-dicarbonyl compound. This imine based multi-component reaction was realized using fully green L-proline nitrate as recyclable room temperature ionic liquid. Recycling of the catalyst was possible up to five runs without loss of catalyst activity. Smaller E-factor (0.255) and process mass intensity (PMI = 3.35), high atom-economy (AE = 89.5%) and reaction mass efficiency (RME = 79.66%) demonstrates the higher environmental compatibility and sustainability of this protocol. DFT calculations showed that the L-proline catalyzed reaction proceeds by three pathways; (i) via proline enamine pathway, (ii) proline mediated aniline enamine pathway or (iii) the pathway involving iminium activation of the aldehyde to provide the Knoevenagel product.