Direct mechanocatalysis by resonant acoustic mixing (RAM)

We demonstrate the use of a metal surface to directly catalyse copper-catalysed alkyne-azide click-coupling (CuAAC) reactions under the conditions of Resonant Acoustic Mixing (RAM) - a recently introduced and scalable mechanochemical methodology that uniquely eliminates the need for bulk solvent, as well as milling media. By using a simple copper coil as a catalyst, this work shows that direct mechanocatalysis can occur in an impact-free environment, relying solely on high-speed mixing of reagents against a metal surface, without the need for specially designed milling containers and media. By introducing an experimental setup that enables real-time Raman spectroscopy monitoring of RAM processes, we demonstrate 0th-order reaction kinetics for several selected CuAAC reactions, supporting surface-based catalysis. The herein presented RAM-based direct mechanocatalysis methodology is simple, enables the effective one-pot, two-step synthesis of triazoles via a combination of benzyl azide formation and CuAAC reactions on a wide scope of reagents, provides control over reaction stoichiometry that is herein shown to be superior to that seen in solution or by using more conventional CuCl catalyst, and is applied for simple gram-scale synthesis of the anticonvulsant drug Rufinamide.

Automated summary

We used a metal surface to directly catalyse copper-catalysed alkyne-azide click-coupling (CuAAC) reactions under the conditions of Resonant Acoustic Mixing (RAM). This mechanochemical methodology eliminates the need for bulk solvent and milling media by relying on high-speed mixing of reagents against a metal surface. The RAM-based direct mechanocatalysis enables the one-pot, two-step synthesis of triazoles on a wide scope of reagents with superior reaction stoichiometry and has been applied for the gram-scale synthesis of the anticonvulsant drug Rufinamide.