Catalyst for Solventless Chemistry
Written by Yilin Xie '26
Edited by Lorenzo Mahoney '24
When you think about “chemistry”, the image that comes to mind is likely an array of test tubes and flasks with various liquids. Indeed, this is the paradigm in chemistry in fluids — solvents — which is widely used in settings from classrooms to industrial plants. However, this is not the only way to control chemical reactions. We can use light and electricity, for example, or apply mechanical force. This last mode of initiating chemical reactions is called mechanical chemistry, or mechanochemistry.
Though mechanochemistry has only been intensely studied relatively recently, one of the iconic images of civilisation — rubbing woods or using flint and steel to make fire — is in fact a mechanochemical reaction . In modern times, mechanochemistry has garnered interest due to its reduced/no use of solvents. While chemistry in fluid solvents rely on the solvent molecules to pull apart the reactants, allowing them to rearrange into the products, mechanochemistry breaks apart the reactants using mechanical forces, eliminating the need for solvents. Since many solvents are considered pollutants, reducing solvent usage reduces our environmental impact.
However, the drastic differences in the environment of mechanochemistry and solvent-based chemistry reactions means that a lot of established techniques for controlling reactions cannot be applied in mechanochemical environments. For example, some catalysts — which are substances that increase the rate of reaction but undergo no net change — used in solvent-based chemistry are ineffective in a mechanochemical environment. To compensate for the lack of accelerant, high temperatures — which also increases the rate of reaction — are needed for reactions to proceed, which does not align with the goal of reducing environmental impact. Thus, there is a demand for developing new catalysts that can function in a mechanochemical setting, therefore making greener reactions viable.
In a 2023 study, Seo et al. did just that . In particular, the researchers looked at Suzuki–Miyaura cross-coupling reactions, which is one of the most prominent modern ways of making C-C bonds in organic chemistry . This type of reaction uses metal-based catalysts, typically palladium (Pd). In a solvent, the catalysts are suspended in the solvent, and therefore can freely interact with the reactants and intermediates, successfully facilitating the reaction. In a solid-state environment, though, the catalyst molecules that are not currently participating in a reaction cycle can quickly aggregate — essentially clump up. This renders them inactive, since they cannot interact with the reactants when they’re bound to other catalyst molecules .
In a metal catalytic complex, there is a metal atom at the centre, then there are groups attached to it, called ligands. Historically, modifications in ligand design have led to many advancements in Pd-catalysed cross-coupling chemistry. Hence, Seo et al. looked at ligands when trying to combat the issue of aggregation. They considered poly(ethylene glycol) (PEG), a polymer, which is a very large molecule in a long, bulky chain. PEG can be attached to a ligand of Pd-catalytic complex, and the bulk of PEG allows it to effectively prevent Pd atoms from crashing into each other, which was what caused them to aggregate. Therefore, by adding these long chains of PEG, the Pd-complexes can be immobilised and suspended just like they would be in a solvent, allowing them to remain separate and functional even as mechanical forces are applied.
In measuring the effects of this modification, Seo et al. found that the catalysts with the modified ligands showed improved efficiency compared to the catalysts used for reaction in solvents. Using an unmodified ligand, they obtained 32% yield in a mechanochemical setting. Using a ligand with a relatively short PEG chain (PEG-400) (400 refers to the average molecular weight of this molecule), the yield increased to 56%. PEG-550, PEG-1000, and PEG-2000 all yielded around 64%, but PEG-4000, a long chain, had a 99% yield.
Previously, the same research team has found that the addition of polymers as additives improves the yield of mechanochemical Suzuki–Miyaura cross-coupling reactions . Compared to the approach in this study, however, Seo et al. found that while there was an improvement when PEG-4000 was directly added (49%, compared to unmodified 32%), it was much lower than when it was attached to the ligand (again, 99%). This clearly demonstrates the advantage of Seo et al.’s new method.
In summary, the addition of PEG chain to a ligand of the Pd catalytic complex successfully prevents the aggregation of the catalyst, overcoming a challenge that is specific to the mechanochemical setting. The longer the chain, the stronger the effect, with PEG-4000 generating a 99% yield. The attachment of the polymer chain to the ligand is also significant, as the polymer chain resulted in less improvement when used as an unattached additive.
This study marks the first development of a mechanochemistry-specific transition-metal catalyst. The incredible high-yield success opens the door for feasible applications of mechanochemical Suzuki–Miyaura cross-coupling reactions, since they are now competitive with the traditional reactions using solvents, with the additional benefits of being solventless and more environmentally friendly. In the grander scheme, this sparks investigations about catalysts designed for other chemical reactions adapted for mechanochemical settings, potentially bringing the mechanochemical version of many other reaction classes to a competitive yield. With hope, these solventless reaction protocols can lead to a new standard in solvent usage level, leading to tremendous change when applied across industries.
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