Temperature controlled, mechanochemical balling milling and twin- screw extrusion Robert R. A. Bolt a , Sarah Raby Buck a , Jamie A. Leitch a , Duncan L. Browne a and Katharine Ingram b a UCL, United Kingdom, b Syngenta, United Kingdom Introduction Whilst primarily mechanochemical reactions are limited to room temperature reactions, their solution counterparts often utilise increased temperatures to improve reaction efficiency as well as reduce reaction times. The addition of heat to mechanochemical reactions has come under increasing interest within the field and has already been demonstrated to have significant positive effects upon the expansion of reaction scopes as well as unlocking new pathway. [1] Results and Discussion At the outset of this project, we aimed to transition away from the stark over-reliance on palladium complexes to more earth-abundant, inexpensive metal systems. This was achieved through the implementation of a controllable heating device to rapidly form new C-C bonds from aryl sulfamate and boronic acid precursors, wherein optimal temperature and heating regimes were determined. [2] Exploration of the scope led to the determination of the reaction’s dependency upon heat to enable C-C bond formation in our nickel-catalysed system. In addition, we have successfully scaled the reaction using twin screw extrusion technology which enabled us to increase product synthesis more than 100-fold to decagram scale. [3]
Conclusions and Outlook It has been demonstrated that the use of temperature-controlled device in conjunction with mechanochemistry can reduce reaction times as well as activate previously inert compounds. Furthermore, it has been shown that the application of this heat system can be readily scaled to a flow‑like system to synthesis on gram scale, and further explorations into this transition is underway. References 1. Seo, N. Toyoshima, K. Kubota and H. Ito, J. Am. Chem. Soc ., 2021 , 143 , 6165–6175 2. Bolt, R. R. A.; Raby‑Buck, S. E.; Ingram, K.; Leitch, J. A.; Browne, D. L. Manuscript in Preparation 3. Bolt, R. R. A.; Leitch, J. A.; Jones, A. C.; Nicholson, W. I.; Browne, D. L. Soc. Rev. , 2022 , 51, 4243-4260
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