Chemical reactions that take place in a ball mill and in the absence of a bulk reaction solvent present different safety profiles to stirred solution reactions. Herein, we present and describe steps that a researcher may take to better ensure that they have considered some of the hazards and measures that emerge and minimize the risk to themselves and their colleagues.

The use of temperature-controlled mechanochemistry to enable the mechanochemical nickel-catalyzed Suzuki-Miyaura coupling is herein described. Transitioning from a capricious room-temperature protocol, through to a heated, PID-controlled programmable jar heater manifold was required to deliver an efficient method for the coupling of aryl sulfamates (derived from ubiquitous phenols) and aryl boronic acid species. Furthermore, this process is conducted using a base-metal nickel catalyst, in the absence of bulk solvent, and in the absence of air/moisture sensitive reaction set-ups. This methodology is showcased through translation to large-scale twin-screw extrusion methodology enabling 200-fold scale increase, producing decagram quantities of C-C coupled material.

No abstract