Recent advances in liquid assisted grinding chemistry: towards sustainable synthesis

Mechanochemistry is undergoing a major renaissance in the fields of chemical and materials science, particularly in terms of synthesis. By injecting a small amount of a liquid into a reaction in a solid state, new mechanochemical technologies, including liquid-assisted grinding (LAG), where a liquid acts like a lubricant, facilitating the contact between solids in the substrate, thereby inducing solution-like areas where the molecules in the substrate solids can react. The screening of polymorphs, cocrystals, solvates, salts, and inclusion compounds has been accomplished through the use of LAG, a modification of conventional neat mechanochemical methods where reactivity is controlled and/or enhanced by the addition of a small amount of liquid. Nevertheless, insufficient research has been conducted on the application of this important technology in the synthesis of organic compounds. This article discusses the latest developments in LAG techniques and the potential of the most common forms of LAG for organic mechanosynthesis, as well as the solvent effect on the nature of the product obtained, the challenges to be overcome, optimal operating conditions, and solvent selection for the LAG processes.