Direct mechanocatalysis using Resonant Acoustic Mixing (RAM)

Abstract

We demonstrate the first example of direct mechanocatalysis by Resonant Acoustic Mixing (RAM), an emerging mechanochemical methodology that eliminates the need for bulk solvent and milling media. By using a simple copper coil as a catalyst, RAM enables the effective one-pot, 2-step synthesis of triazoles via a combination of benzyl azide formation and copper-catalyzed alkyne-azide click-coupling (CuAAC), on a wide scope of reagents, providing excellent control over reaction stoichiometry, and enabling a simple synthesis of the anticonvulsant drug Rufinamide.

Direct Mechanocatalysis without Milling Media – From Mixer Mills to Resonant Accoustic Mixers

“…Hence, we transferred the system to a RAM that can mix substrates without milling media in a more efficient manner. [16] To facilitate this, we designed a custom 25 mL milling vessel and holder for a LabRAM II (see ESI, Fig. S2).…”

“…The addition of the right amount of LAG, is critical for reaching an rheology and conversion of substrates (η-sweet spot). [10] Furthermore, we extend this concept of media-free milling to a resonant acoustic mixer (RAM), which currently emerges as a promising technology for mechanochemistry (co-crystallization [11,12] , functional materials [13] , nanoparticles [14] , MOF-synthesis [15] , and catalytic reactions [16,17] ) because it enables rapid and efficient mixing. [17,18] RAM intrinsically avoids the use of grinding media, and so the problem of product contamination due to grinding media abrasion [12,17] and provides a better scalability compared to classical ball mills.…”

THETA as an Efficient Cu-Binding Ligand for Manual and Automated “Click” Synthesis: the Rufinamide Case

“…The synthesis of rufinamide has served as a testing ground for modern organic synthesis technologies, including flow chemistry, − mechanochemistry − and automated synthesis. , The last one uses programmable robots (e.g., Chemical Processing Unit ChemPU) designed for chemical synthesis to carry out multistep synthetic procedures. The scale-up of rufinamide synthesis has evolved into a platform for discussing a broad array of factors contributing to modern drug synthesis, including efficacy, ecology, logistics, and economy .…”