ABSTRACT Knoevenagel condensation reaction is a crucial C─C bond formation reaction in organic synthesis, providing access to diverse biological and industrial intermediates. Although catalyst‐free protocols for this reaction have been explored, they often suffer from sluggish kinetics and limited substrate scope, typically restricted to aromatic aldehydes. Herein, we explore a family of basic ionic liquids (ILs) synthesized from naturally occurring pyridine carboxylic acid as an organocatalyst for Knoevenagel condensation. The presence of a carboxylate group adjacent to pyridine in the catalyst significantly enhances its efficiency, enabling solvent‐free reactions under mild conditions, with ultralow IL loadings (∼ 0.2 mol%). DFT calculations revealed that the pyridine‐assisted pathway is energetically favorable compared to the carboxylate‐mediated route. The designed system is an efficient and reusable organocatalyst for Knoevenagel condensation, catering to a broad substrate scope including aromatic, heterocyclic, and less electrophilic aliphatic aldehydes. Moreover, this protocol enables the green synthesis of bioactive tetrahydrobenzobpyrans via a one‐pot, three‐component reaction. Calculated green metrics further validated the practical applicability of the catalytic protocol, toward the sustainable production of industrially relevant molecules, as the calculated E ‐factor value of 0.16 aligns with reported IL‐based green protocols.
Jungi et al. (Thu,) studied this question.