Two step synthesis, characterization and anti-bacterial activity of series of dihydroisobenzofuran-5-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl) pyrazine/pyrimidines

The synthesis of heterocyclic compounds has garnered significant attention due to their diverse pharmacological activities. Imidazole and pyrazine derivatives are particularly prominent for their antibacterial properties, making them valuable targets in medicinal chemistry. The incorporation of is benzofuran and pyridine scaffolds further enhances the biological potential of these molecules. The condensation and cyclization of functionalized intermediates with aldehydes represent an effective route for developing novel heterocyclic compounds. The study describes the synthesis of dihydroisobenzofuran-pyridine-based imidazole-pyrazine/pyrimidine derivatives through a multi-step reaction sequence. The reaction of 1-(1,3-dihydroisobenzofuran-5-yl)-2-(pyridin-2-yl) ethan-1-one (1) and its corresponding ethenol (2) with sodium nitrite in acetic acid yielded compound 3. Compound 3 was further subjected to condensation and cyclization reactions with various carbaldehydes (4a–f), resulting in the formation of the desired heterocycles (5a–f). These synthesized derivatives were characterized using advanced spectral techniques, confirming their structures. Preliminary screening of the compounds revealed promising antibacterial activity. This study highlights the successful synthesis of novel dihydroisobenzofuran-pyridine-based heterocycles using a streamlined condensation-cyclization process. The synthesized dihydroisobenzofuran-imidazole-pyrazine/pyrimidine derivatives (5a–f) were thoroughly characterized through techniques such as 1 H-NMR and mass spectrometry, confirming their chemical structures. Biological evaluation demonstrated that these compounds exhibited antibacterial activity against E. coli and S. aureus. Notably, compounds 5c, 5f and standard drug of chloramphenicol displayed significant potency, with minimum inhibitory concentration (MIC) values indicating strong antibacterial efficacy. The findings regarding compounds 5c and 5f highlight their potential as promising candidates for therapeutic development against bacterial infections, demonstrating superior efficacy compared to the current market available drug of chloramphenicol.