Green synthesis and catalytic efficiency of [BCMAB][2Cl] ionic liquid for the synthesis of bioactive 1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives <i>via</i> Biginelli condensation: BSA binding affinity and molecular docking studies

A newly developed ionic liquid (IL) catalyst, 1,4-bis(carboxymethyl)benzene-1,4-diaminium chloride ([BCMAB][2Cl]), was synthesized via a straightforward reaction between p-phenylenediamine and chloroacetic acid. This eco-friendly catalyst efficiently promotes multicomponent reactions (MCRs) such as Biginelli, Hantzsch, and Niementowski syntheses to yield 1,2,3,4-tetrahydropyrimidine-5-carboxylates, while eliminating the use of hazardous volatile organic solvents. The IL was thoroughly evaluated with the help of Fourier transform-infrared (FT-IR), powder-X-ray diffraction (PXRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) methods, demonstrating its stability in both air and water. Its acidity was found to play a pivotal role in catalytic performance, with [BCMAB][2Cl] outperforming other tested ILs in catalytic activity. The synthetic protocol is cost-effective, environmentally benign, and sustainable, as validated by green chemistry parameters, including E-factor, atom economy, reaction mass efficiency, and process mass intensity. Furthermore, the IL catalyst is reusable without significant loss of activity, simplifying product recovery. The reactions were carried out under reflux conditions, efficiently synthesizing bioactive compounds from heterocyclic aldehydes, methyl acetoacetate, and urea. The resulting compounds (4a–k) were analyzed for their binding interaction with bovine serum albumin (BSA) via molecular docking. Compounds 4a, 4g, and 4i exhibited the strongest binding affinities, while all derivatives demonstrated significant docking scores and notable BSA binding activity. Overall, these findings underline the dual functionality of [BCMAB][2Cl] as both an effective catalyst and a promoter of biologically active compounds.