Eco-Friendly Preparation of Quinazolinone and Spiroquinazolinone Derivatives in Water Using Surfactant Assisted Method

Abstract

An environmentally safer and efficient method has been developed for the synthesis of quinazolinone and spiroquinazolinone derivatives in aqueous medium using a surfactant-assisted catalytic system. The present work mainly focuses on the use of water as green solvent along with Triton X-100 surfactant and L-proline as organocatalyst for carrying out multicomponent reactions under mild reaction conditions. Quinazolinone derivatives are known for a wide range of biological activities and therefore continue to attract attention in medicinal and synthetic chemistry. In the developed method, isatoic anhydride, substituted benzaldehydes or isatins, and different primary amines were reacted smoothly at room temperature to afford the desired products in good to excellent yields. The use of surfactant played an important role in improving the solubility of reactants in water by formation of micelles, which enhanced the reaction efficiency significantly. A series of quinazolinone and spiroquinazolinone analogues were synthesized and characterized using IR, ¹H NMR, ¹³C NMR and mass spectroscopic techniques. The effect of substituents on reaction progress was also studied and it was observed that electron withdrawing groups reduced the reaction rate while halogen substituted substrates reacted more efficiently. The present protocol offers several advantages such as easy workup, reduced reaction time, avoidance of toxic organic solvents, simple purification process and ecofriendly reaction conditions. Due to operational simplicity and greener nature, the developed synthetic procedure may become useful for future preparation of biologically active quinazolinone based heterocyclic compounds.