Recent Advances in the Synthesis of Quinazoline Derivatives

Abstract

Quinazoline is a privileged nitrogen-containing heterocyclic scaffold of considerable importance in medicinal and pharmaceutical chemistry. This review critically summarizes representative synthetic approaches to quinazoline derivatives, covering foundational reports through studies published up to 2025. The literature is organized primarily according to the nature of the starting materials and synthetic strategy, allowing related transformations to be compared systematically. Classical cyclocondensation methods are discussed alongside modern approaches, including multicomponent reactions, oxidative annulations, transition-metal-catalyzed transformations, microwave- and ultrasound-assisted reactions, and green synthetic protocols. Comparative analysis shows a clear evolution from conventional high-temperature and multistep procedures toward milder, more efficient, selective, and sustainable methods. Recent one-pot, atom-economical, and recyclable catalytic systems frequently provide broader substrate scope, improved yields, shorter reaction times, simpler operation, and reduced environmental impact. Nevertheless, important challenges remain, including the development of more general and economical protocols, improved regioselectivity, greater use of readily available starting materials, reduced dependence on costly or environmentally undesirable reagents and catalysts, and reliable scalability. This review therefore provides a structured assessment of current synthetic options and highlights opportunities for more practical and sustainable access to structurally diverse quinazoline derivatives.