Metal‐Catalyzed Organic Reactions by Resonant Acoustic Mixing**

Abstract

We demonstrate catalytic organic synthesis by Resonant Acoustic Mixing (RAM): a mechanochemical methodology that does not require bulk solvent or milling media. Using as model reactions rutheniumcatalyzed ring-closing metathesis and copper-catalyzed sulfonamide-isocyanate coupling, RAM mechanosynthesis is shown to be faster, operationally simpler than conventional ball-milling, while also providing the first example of a mechanochemical strategy for rutheniumcatalyzed ene-yne metathesis. Reactions by RAM are readily and directly scaled-up without any significant changes in reaction conditions, as shown by the straightforward 200-fold scaling-up of the synthesis of the antidiabetic drug Tolbutamide, from hundreds of milligrams directly to 30 grams.

Methods for Monitoring Milling Reactions and Mechanistic Studies of Mechanochemistry: A Primer

“…73 The systematic analysis of the coupling reactions conducted by RAM, as well as ball milling, revealed the appearance of an "η sweet-spot", i.e., an η-value at which the reaction conversion at a given time achieves a maximum (Figure 3). 73,74 Single time point analysis has been used extensively in development and screening of mechanochemical organic synthesis, with recent examples including screening of the catalyst and reaction scope for catalytic coupling of an amine, aldehyde, and acetylene 75 ("A3 coupling", Figure 4), creation of a protocol for mechanochemical ruthenium-catalyzed olefin metathesis, or development of a solvent-free activation of noble metals. 76,77 Notably, single time point analysis was used by the Mack and Blair groups to gain fundamental insight into energy delivery in mechanochemical reactions, by recording the conversion of Diels−Alder reactions conducted in milling assemblies made of different materials and at different frequencies.…”

“…The appearance of an η-sweet-spot is observed for reactions by (a) RAM and (b) ball milling. Adapted from ref . Copyright 2022 Wiley.…”

Mecanoquímica: una herramienta importante en la reactividad en el Estado Sólido

“…Los equipos especializados en MAR generan energía acústica la cual es producida por la acción de oscilación de resortes que inducen resonancia mecánica y cuya frecuencia es transferida directamente al recipiente de la muestra originando zonas de mezclado locales (Michalchuk et al, 2018;Solares-Briones et al, 2021). Recientemente Friščić y colaboradores han demostrado los beneficios de la técnica MAR en reacciones orgánicas catalizadas por metales (Gonnet et al, 2022).…”

Resonant Acoustic Mixing (RAM) for Efficient Mechanoredox Catalysis without Grinding or Impact Media

“…So far, RAM has been used for synthesis of cocrystals, 8,9 a metal-organic frameworks (MOFs), as well as metal-catalysed catalytic coupling reactions. 10,11 In contrast to ball-milling, RAM reaction design is simplified by the absence of grinding media and reactions were shown to be readily scalable by at least 100-fold. 11…”

“…Infrared spectra of tetrahedral borate (BO4 -) moieties are known to show an asymmetric B-O stretching band around 900-1100 cm -1 , depending on their chemical environment. 15 In order to verify the presence of boron species in the recycled BaTiO3 material, a sample of the BaTiO3 mechanoredox catalyst after one cycle was analysed by 11 B solid-state NMR (ssNMR) spectroscopy, which revealed a signal centered at -0.77 pm with respect to boric acid (Figure 2d). The 11 B signal exhibited cubic symmetry, overall consistent with a tetrahedral BO4species.…”