Exploring stable, sub-ambient temperatures in mechanochemistry via a diverse set of enantioselective reactions

Mechanochemistry/mechanical chemistry is a field that deals with athermal or ultra-fast chemical reactions between solids or between solids and surrounding gaseous or liquid molecules under mechanical forces. Generally, it can be seen as the interface between chemistry and mechanical engineering. In most cases, the ball milling technique is the most widely used process through which mechanical force is used to achieve chemical processing and transformations. The impact of mechanochemistry has been rapidly growing. Recent advancements in high throughput milling technology has further facilitated more discoveries in this field. However, it remains necessary to continue developing a better understanding of mechanochemical systems with respect to energetics and mixing.

Scientists from the Department of Chemistry at University of Cincinnati: Dr. Joel Andersen, Dr. James Brunemann and led by Professor James Mack reported before a study on sub-ambient milling temperatures, however, in their initial study they explored a single reaction, which possess low activation barrier in addition to being exothermic.  Nevertheless, the results were illuminating but still warrant further exploration and investigation. Recently developed capabilities for performing mechanochemistry below ambient temperatures offer an opportunity for strengthening the fundamental understanding of energetics in mechanochemical systems. In this context, Professor James Mack and his colleagues proposed to further explore the recently presented fundamentals by applying a unique reactor modification to reactions both new and old in mechanochemical literature, looking back in one case to explain observations made more than ten years ago. In addition, their focus was to further expand the scope of that work by examining a diverse set of reactions. Their work is currently published in the research journal, Reaction Chemistry & Engineering.

Basically, their investigation included proline-catalyzed aldol reactions; enantioselective multicomponent reactions between an aldehyde, an amine and an alkyne; and Diels Alder reactions. Their endeavor was made possible by both by the choice of mill (mixer mill, one ball) as well as the modifications made to allow frequency control and temperature control.

The authors reported that the new system allowed for independent control of temperature and frequency effects, which in the past have been often conflated and can make interpretation challenging or impossible. Remarkably, with respect to the relationship between the operating frequency and the efficient mixing of reactants, they were able to propose the term “mixability coefficient” to describe the ease or difficulty of interparticle mixing.

In summary, University of Cincinnati researchers successfully explored the effects of temperature and frequency in mechanochemical systems by controlling them in isolation from one another. In the system they introduced, evidence for the isolation of the two variables was given by the lack of change in yield and enantioselectivity of a diverse set of reactions when frequency is changed at constant temperatures. Overall, their study improved and strengthened the fundamental understanding of energetics in mechanochemical systems.