Mechanochemistry vs Conventional Solid-State Synthesis: A Sustainable Development Pathway

The shift to sustainable chemical manufacturing highlights the need for solid-state synthesis methods that minimize solvent use, energy consumption and environmental impact. This review summarizes mechanochemistry and cocrystal-assisted strategies as alternatives to conventional high temperature solid-state synthesis routes. Mechanochemical activation enable rapid, selective and solvent free transformations by creating highly reactive local environments, while cocrystal engineering improves molecular organization, lower activation barriers and enhances polymorph control. These methods together access the reaction pathways, metastable phases and product selectivity that are often difficult to obtain by thermal or solution methods. A comparison shows clear differences from mechanochemical and conventional solid-state synthesis from energy input, reaction kinetics, phase selectivity and sustainability. In recent years, many advances including continuous manufacturing such as liquid-assisted grinding (LAG), in-situ mechanism research and twin-screw extrusion, show that mechanochemistry has increasing scalability and industrial importance. However, there are still challenges in mechanistic understanding, equipment dependence and specific system kinetic limitations. Overall, mechanochemical and cocrystal-assisted synthesis provide a selective, efficient and sustainable method that can complement conventional solid-state synthesis methods. In some cases, it partly replace conventional methods. The continued development of these technologies may influence future materials discovery, pharmaceutical solid form design and industrial scale sustainable manufacturing.