Volume 241, 2023

The “η-sweet-spot” (ηmax) in liquid-assisted mechanochemistry: polymorph control and the role of a liquid additive as either a catalyst or an inhibitor in resonant acoustic mixing (RAM)

Abstract

Resonant acoustic mixing (RAM) offers a simple, efficient route for mechanochemical synthesis in the absence of milling media or bulk solvents. Here, we show the use of RAM to conduct the copper-catalysed coupling of sulfonamides and carbodiimides. This coupling was previously reported to take place only by mechanochemical ball milling, while in conventional solution environments it is not efficient, or does not take place at all. The results demonstrate RAM as a suitable methodology to conduct reactions previously accessed only by ball milling and provide a detailed, systematic overview of how the amount of liquid additive, measured by the ratio of liquid volume to weight of reactants (η, in μL mg−1), can affect the course of a mechanochemical reaction and the polymorphic composition of its product. Switching from ball milling to RAM allowed for the discovery of a new polymorph of the model sulfonylguanidine obtained by catalytic coupling of di(cyclohexyl)carbodiimide (DCC) and p-toluenesulfonamide, and the ability to control reaction temperature in RAM enabled in situ control of the polymorphic behaviour of this nascent product. We show that the reaction conversion for a given reaction time does not change monotonically but, instead, achieves a maximum for a well-defined η-value. This “η-sweet-spot” of conversion is herein designated ηmax. The herein explored reactions demonstrate sensitivity to η on the order of 0.01 μL mg−1, which corresponds to an amount of liquid additive below 5 mol% compared to the reactants, and is at least one to two orders of magnitude lower than the η-value typically considered in the design of liquid-assisted ball milling mechanochemical reactions. Such sensitivity suggests that strategies to optimise liquid-assisted mechanochemical reactions should systematically evaluate η-values at increments of 0.01 μL mg−1, or even finer. At η-values other than ηmax the reaction conversion drops off, demonstrating that the same liquid additive can act either as a catalyst or an inhibitor of a mechanochemical reaction, depending on the amount.

Graphical abstract: The “η-sweet-spot” (ηmax) in liquid-assisted mechanochemistry: polymorph control and the role of a liquid additive as either a catalyst or an inhibitor in resonant acoustic mixing (RAM)

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
22 jun 2022
Accepted
08 aug 2022
First published
08 aug 2022

Faraday Discuss., 2023,241, 128-149

The “η-sweet-spot” (ηmax) in liquid-assisted mechanochemistry: polymorph control and the role of a liquid additive as either a catalyst or an inhibitor in resonant acoustic mixing (RAM)

L. Gonnet, T. H. Borchers, C. B. Lennox, J. Vainauskas, Y. Teoh, H. M. Titi, C. J. Barrett, S. G. Koenig, K. Nagapudi and T. Friščić, Faraday Discuss., 2023, 241, 128 DOI: 10.1039/D2FD00131D

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