Catalyst- and solvent-free multicomponent synthesis of dihydropyridines from biomass-derived building blocks

The use of biomass-derived building blocks as sustainable alternatives to petrochemical substrates is gaining relevance in fine chemical synthesis. In this work, we explore the solvent- and catalyst-free multicomponent Hantzsch reaction using biomass-based aldehydes—vanillin and furfural—to synthesize 1,4- and 1,2-dihydropyridines. Vanillin enabled selective product formation depending on temperature: 1,2-dihydropyridines were obtained at 20 °C under kinetic control, while 1,4-dihydropyridines predominated at 80 °C under thermodynamic control. The resulting 1,2-dihydropyridines showed resistance to further aromatization. In contrast, furfural consistently yielded 1,4-dihydropyridines regardless of temperature, due to its higher reactivity. Twelve compounds were synthesized, three of which are novel. Yields ranged from 69 % to 92 %. The process aligns with green chemistry principles, as confirmed by Green Metric indicators such as Atom Economy (AE), E-factor (EF), and Product Mass Intensity (PMI). Sustainability was further visualized through radial pentagon diagrams for representative reactions.