One–Pot Synthesis of Quinazolin–4(3H) –ones Catalyzed by 2,4,6–Trichloro–1,3,5–triazine (TCT) Under Solvent–Free Conditions

An efficient and environmentally benign one-pot synthesis of quinazolin-4(3H)-ones has been developed using 2,4,6-trichloro-1,3,5-triazine (TCT) as a cost-effective and commercially available catalyst under solvent-free conditions. This methodology involves a three-component reaction of anthranilic acid, diverse amines, and formic acid, proceeding smoothly in a single step without the need for intermediate isolation. The catalytic role of TCT significantly enhances reaction efficiency while maintaining mild conditions (room temperature), making the process both energy-efficient and operationally simple. Key advantages of this protocol include short reaction times (50–70 min), excellent product yields (88–95%), and broad substrate compatibility, accommodating both electron-donating and electron-withdrawing substituents on aromatic amines. The solvent-free approach aligns with green chemistry principles by eliminating hazardous organic solvents, reducing waste, and simplifying purification. Furthermore, the method avoids the use of expensive or moisture-sensitive reagents, addressing common limitations of traditional quinazolinone syntheses, such as harsh conditions, prolonged reaction times, and low yields. The synthesized quinazolin-4(3H)-ones are of significant pharmaceutical interest due to their diverse biological activities, including anticancer, antimalarial, and anti-inflammatory properties. This work not only provides a practical and scalable synthetic route but also highlights the potential of TCT as a versatile catalyst for multicomponent reactions. The combination of mild conditions, high atom economy, and environmental sustainability makes this protocol a valuable addition to the synthetic toolbox for medicinal and heterocyclic chemistry.