Mechanosynthesis of N-heterocyclic compounds via ball milling

Mechanochemistry, an emerging synthetic strategy that utilizes mechanical forces to drive chemical transformations, has attracted significant attention due to its advantages of solvent minimization, high efficiency, and environmental sustainability. Unlike conventional solution-based methods, mechanochemical transformations are driven by friction, shear, and impact generated by mechanical energy, offering unique opportunities for accessing novel reactions and materials. Diverse techniques, including grinding, extrusion, and ball milling, have been extensively employed in organic synthesis, materials science, and pharmaceuticals, and a number of relevant review articles have been published covering a large variety of achievements over the past two decades. This review specifically focuses on the application of ball milling in the construction of nitrogen-containing heterocyclic small molecules, many of which are pivotal structural motifs in pharmaceuticals, bioactive molecules, functional materials, and fine chemicals. By highlighting representative examples and future prospects, this review aims to inspire further innovations in sustainable synthetic methodologies and broaden the scope of mechanochemistry in heterocyclic chemistry.