Solvent-free Synthesis, Characterization, and Antimicrobial Evaluation of Ethyl 7-Phenyl-5-Propyl-4,7-dihydro- [1, 2, 4]triazolo[1,5-a]pyrimidine-6-carboxylate Derivatives

Introduction: The development of multi-drug-resistant microbial strains requires the need to develop new antimicrobial drugs. Green chemistry methods provide environmentally sustainable strategies to develop pharmacologically active compounds. To synthesize a series of novel ethyl 7-phenyl-5- propyl-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate derivatives and evaluate their antibacterial and antifungal properties. Materials and Methods: The one pot, solvent-free process was used for the preparation of 4a-j from the reaction of benzaldehyde derivatives (1a–j), ethyl 3-oxohexanoate (2), and 1H-1,2,4-triazol-5-amine (3) at 140 °C for 20-25 minutes. The products were characterized by melting point, TLC and spectral data. Antibacterial and antifungal activities were assessed using standard biological screening methods. Results: The solvent-free conditions afforded good purity, efficient products. Compounds 4g, 4d, and 4f showed good antibacterial activity against Streptococcus pyogenes and Staphylococcus aureus. Compounds 4g, 4c showed good antifungal activity against Candida albicans. Discussion: The solvent free synthesis brought forth triazolopyrimidine derivatives efficiently. Spectra validated their structure. Antimicrobial screening brought forth that hydroxyl- (4g) and halogen-substituted derivatives (4d, 4f) possessed better antibacterial activities, while derivatives 4g and 4c were more antifungal. These observations depict that proper substitutions on aromatic rings bring forth consequences on bioactivities, thus, optimizing structural features on this system will open new ways. Conclusion: The developed eco-friendly synthetic method provides viable route for synthesising novel triazolopyrimidine derivatives with significant antimicrobial potential, highlighting its promise for future drug development.