Solid-state dynamic combinatorial chemistry: reversibility and thermodynamic product selection in covalent mechanosynthesis

Abstract

We demonstrate the reversibility and thermodynamic control in covalent mechanosynthesis, by using the base-catalysed metathesis of aromatic disulfides as a model reaction. The mechanochemical formation of thermodynamic equilibrium mixtures is observed for both neat and liquid-assisted grinding methodologies. Different methodologies lead to mutually different equilibrium compositions, which also differ from those obtained by solution equilibration. The differences can be explained in terms of crystal packing effects superimposed onto the inherent reactivity of isolated molecules. Calculations indicate that the differences in relative energies of reactants and products in their respective crystal structures can bias the mechanochemical reaction equilibrium towards the complete conversion of reactants into the product, in that way opening the doors for the development of dynamic combinatorial synthesis in the solid state and for the rational design of solid-state synthesis using mechanochemistry.