In recent years, mechanochemistry has been growing into a widely accepted alternative for chemical synthesis. In addition to their efficiency and practicality, mechanochemical reactions are also recognized for their sustainability. The association between mechanochemistry and Green Chemistry often originates from the solvent-free nature of most mechanochemical protocols, which can reduce waste production. However, mechanochemistry satisfies more than one of the Principles of Green Chemistry. In this Review we will present a series of examples that will clearly illustrate how mechanochemistry can significantly contribute to the fulfillment of Green Chemistry in a more holistic manner.

Chemoenzymatic oligomerisation of l-amino acids was successfully developed using mechanochemical techniques.

The ability of mechanochemistry to alter established chemical selectivity is demonstrated. A copper(I)-catalyzed mechanochemical aldehyde/alkyne/amine coupling using calcium carbide as the acetylene source provides selective access to 1,4-diamino-2-butynes, which contrasts classical approaches that provide propargylamine-type products. Solventless milling conditions were found to be essential to unmask A coupling products with new compositions.

Mechanochemical chemoenzymatic peptide and amide bond formation catalysed by papain was studied by ball milling.