Advancing the Reactivity and Selectivity in Covalent and Coordination Mechanochemistry by Thermally-Controlled Milling

Milling under controlled and variable heating programs introduces a new level of mechanochemical reactivity beyond what can be achieved by conventional mechanochemical or solution procedures. The methodology is demonstrated on three different systems: C–C bond forming Knoevenagel condensation, selective C–N bond formation for amide/urea synthesis, and solid-state formation of an archetypal open metal-organic framework, MOF-74. In all cases, the application of specific heating regimes enabled significant acceleration of milling reactions and increased overall energy efficiency, use of much milder milling conditions, and unprecedented product selectivity, best demonstrated on the one-pot selective synthesis of four complex products containing combinations of amide, amine or urea functionalities from the same and simple acyl azide and diamine reactants. Principal control over this enhanced reactivity and selectivity stemmed from the application of specific heating regimes to mechanochemical processing accomplished by a new, in-house developed mechanochemical reactor. As even the moderate increase in temperature strongly affects the selectivity and the rate of mechanochemical reactions, the results presented are in line with recent challenges of the accepted theories of mechanochemical reactivity.