Greening Chemistry is a series of opinion columns, written by a rotating group of contributors.
While addressing a group at the Organic Reactions and Processes Gordon Research Conference in June, Zachary Wickens, an associate professor at the University of Wisconsin–Madison, posed a question: “How do you make a new chemical building block common in synthetic chemistry?” He used the analogy of vinyl esters, epoxides, and other reagents that at the time of their discovery were unique but now are so common that they might appear even in undergraduate textbooks.
This conversation prompts another question, How do you take an emerging technology and make it a common laboratory tool? This is a challenge mechanochemists have yet to solve.
“Some chemists find joy in the invigorating, if head-scratching, conversations about what mechanochemistry can do without solvents. Others see the field as borderline heretical and challenge its feasibility.”
Mechanochemistry, a method of driving chemical reactions using mechanical forces like grinding and milling, could vastly improve the sustainability of the chemical enterprise. It offers the potential for simpler operation, safer practices, shorter reaction times, and improved waste profiles. Yet uptake of mechanochemistry over the past 25 years has been sluggish.
Science doesn’t appear to be the primary obstacle. For example, Evelina Colacino, an associate professor at the University of Montpellier, and coworkers were able to synthesize the antibiotic nitrofurantoin mechanochemically. A follow-up study from Sabrina Spatari, a professor at the Israel Institute of Technology, developed a method that reduces both waste and production costs—from about $38/kg to $5/kg. Instead, the problem appears to be an unwillingness to embrace mechanochemistry as an opportunity.
While other emerging technologies such as photochemistry, microwave chemistry, and electrochemistry had their hurdles, none have had the same struggle in adoption as mechanochemistry. That’s because mechanochemistry requires us to sidestep solvents, which are tied to the fundamentals of chemical practice. We teach students about solubility rules in general chemistry and solvent selection criteria in organic chemistry. In labs we talk about the inability for nondissolved solids to participate in reactions. Mechanochemistry encourages us to challenge these concepts directly.
Some chemists find joy in the invigorating, if head-scratching, conversations about what mechanochemistry can do without solvents. Others see the field as borderline heretical and challenge its feasibility, despite the data aligning with traditional methods.
This skepticism harkens back to other groundbreaking ideas celebrated only in hindsight. Consider Galileo Galilei, who faced life imprisonment for endorsing Copernicus’s theory that Earth orbits the sun. Or Alfred Wegener, who encountered outright hostility for proposing that the continents were once all connected and drifted across the planet. And then there’s quantum mechanics and the idea of quantum entanglement, which Einstein derided as “spooky action at a distance.”
These historical examples highlight not just a clash of ideas but also the hostility directed toward the individuals advocating for them. To foster the growth of mechanochemistry, it’s essential to alleviate the apprehension linked with embracing change, especially something as stressful as mastering an entirely new paradigm.
Artificial intelligence is one example of how these struggles with adoption still happen. There are some early adopters who see it as an opportunity, some pessimists who view it as a threat, while most of us slowly learn how this might fit into our lives. Broken down into usable systems, AI has become better understood and a common application, including Google’s Gemini search tool and Anthropic’s Claude for literature scouring.
Similarly, if we can lower the barrier to entry to mechanochemistry through unifying terminology and simplifying tools and equipment access, it can become a synthetic chemist’s go-to. The truth is, a lot of the principles of mechanochemistry are the same as those of solution-phase chemistry. The reagents, analytical methods, purification techniques, and even in some cases mechanisms are very similar if not identical to solution methodologies—all of which makes it less daunting than it seems to massage mechanochemistry into the synthetic workflow. A place where we need improvement in terminology can be related to acidity and basicity. Fundamentally, the measurements of acid or base strength are tied to concentration (unit per volume), which in solvent-free environments can be tricky to define.
Through advances in mechanochemistry, we’ve already been able to explore new opportunities for reaction outcomes due to the unique parameters mechanochemistry introduces. Fresh perspectives on mechanisms and reaction rules, access to reagents that were previously inaccessible without meeting difficult conditions, and exciting engineering advancements in what tools can become valuable are all enabled by the doors mechanochemistry opens. We’re able to explore this space because of the adjacent possible. You never thought to dip your fries in a milkshake until you had them both sitting next to each other on the table, or until a friend said it was amazing. Similarly, we never thought of using raw minerals as reagents or rock tumblers as reactors until mechanochemistry opened our eyes to the possibility. With continued exploration of this new play space of possibilities, mechanochemistry could continue to unlock chemical geography we never knew was present.
Isaiah Speight Credit:
Courtesy of Isaiah Speight
Despite the challenges and detractors, we eventually came to adopt the concepts of a sun-centric solar system, continental drift, and quantum mechanics. With time, mechanochemistry will find its comfort in the chemical toolbox—if chemists can find comfort in change and embrace the adjacent possible rather than the localized real.
James Mack Credit:
Courtesy of James Mack
Isaiah Speight is an assistant professor at William and Mary and a principal investigator at the National Science Foundation’s Center for the Mechanical Control of Chemistry.
James Mack is a professor of chemistry at the University of Cincinnati and a principal investigator at the National Science Foundation’s Center for Mechanical Control of Chemistry.
Views expressed are those of the authors and not necessarily those of C&EN or ACS.
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