Efficient Synthesis and Optimization of 1,4-Dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine Derivatives Using a Three–Component Reaction

The synthesis of 1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine derivatives (DTRT 1 to 5) was successfully achieved through a three-component reaction involving N-aryl-1H-pyrazole-4-carbaldehydes (1a–1e), 2-aminobenzimidazole (2), and acetylacetone (3) which was carried out under reflux in methanol. Triethylamine (5 mol %) was used as a catalyst to facilitate the reaction at 75–80°C with continuous stirring, and the progress was monitored via thin-layer chromatography (TLC). After completion, the reaction mixture was cooled, leading to product precipitation, followed by vacuum filtration and recrystallization for purification. To optimize reaction conditions, various solvents and reaction times were examined. Methanol proved to be the most effective solvent, yielding 91% of the product in 12 h, compared to other solvents like ethanol, ethyl acetate, acetonitrile, and DMF, which required longer reaction times and resulted in lower yields. Spectroscopic analysis using 1H and 13C NMR confirmed the successful formation of the desired compounds. This study highlights methanol as the optimal solvent for achieving high yields in a shorter time, making the reaction more efficient and suitable for larger-scale applications.