Recent advances in non-conventional synthesis of N-heterocyclic compounds: emerging strategies and biological perspectives

Abstract

Nitrogen-containing heterocycles are of particular research interest as they are commonly found in naturally occurring bioactive molecules. However, traditional synthetic approaches to these compounds have various drawbacks, including slow reaction rates, harsh reaction conditions (e.g., high temperatures or strong acids), and low product yields. In recent years, non-conventional synthetic methods, such as microwave irradiation, sonochemical synthesis, and mechanochemical approaches, have emerged as efficient and sustainable alternatives. These techniques provide multiple benefits in synthetic chemistry, enabling faster reactions, enhanced product yields, and superior reaction selectivities. Moreover, they reduce the reliance on toxic solvents and lower the overall energy requirements, ultimately leading to more sustainable processes. Furthermore, the application of green chemistry principles in the synthesis of N-heterocycles has enhanced their environmental compatibility. This review focuses on recent advancements in non-conventional synthetic strategies for constructing N-heterocyclic compounds. Key scaffolds discussed include pyridines, pyrrolidines, pyrroles, imidazoles, pyrazolines, indoles, pyrazoles and 1,2,3-triazoles, along with their fused analogs. These alternative approaches are noted for their synthetic efficiency and environmentally benign nature. Furthermore, the resulting heterocycles exhibit significant potential as biologically active molecules, particularly in the context of their antimicrobial, anticancer, and antioxidant activities.