Liquid‐Assisted Grinding Mechanochemistry in the Synthesis of Pharmaceuticals

Mechanochemical reactions by milling, grinding or other types of mechanical action have emerged as a salient green approach because of its wide applications towards academic and industrial chemical communities in sustainable solvent-free/solvent-less processes. Liquid-assisted grinding (LAG) as an extension of traditional solvent-free mechanochemical techniques by which a small amount of liquid is used as an additive to enhance and/or control reactivity, has been fruitfully applied in the screening of inclusion compounds, cocrystals, salts, solvates, and polymorphs. However, utilization of this important technique in the synthesis of pharmaceutically and biologically relevant targets was not adequately investigated. This review article summarizes an overview of the latest development of LAG mechanochemical approaches in the synthesis of active pharmaceutical ingredients (API) and drug-like fragments, highlights its superiority versus conventional syntheses.