The role of liquid amount in organic mechanochemical reactions investigated by resonant acoustic mixing (RAM) Linda Bechnak a , Robin S. Stein b , Hatem M. Titi a , Stefan Koenig c , Karthik Nagapudi c and Tomislav Friščić a a Department of Chemistry, McGill University, Canada, b MC2 Facility, NMR/EPR,McGill University, Canada, c Genentech, One Dna Way, South San Francisco, USA Although mechanochemistry has been established as a powerful tool for green and sustainable synthesis 1-3 , parameters that control the outcome of mechanochemical reactions are not yet well understood. One important parameter is the liquid additive, known to frequently strongly influence mechanochemical reaction pathways. Whereas a limited amount of work has been dedicated to the role of liquid amount, expressed as the parameter η , in context of cocrystallization, 4,5 there are little to no studies in the context of organic mechanochemical transformations. 6 This work investigates how the amount of liquid additive affects mechanochemical organic reactions, based on resonant acoustic mixing (RAM) technique 7,8 and Schiff base condensation as a model reaction. The reaction model chosen allowed us to study the effect of η on the stoichiometric outcome as well, providing a rare example of a systematic study capable of directly comparing neat reactions to those conducted at low η values (identical to those used in liquid-assisted grinding), as well as slurry and solution conditions. References 1. Do, J.-L.; Friščić, T. ACS Cent. Sci. 2017 , 3 , 13-19.
2. Andersen, J.; Mack, J. Green Chem . 2018 , 20 , 1435-1443 3. Moores, A. Curr. Opin. Green Sustain. Chem. 2018 , 12 , 33-37. 4. Friščić, T. et al . CrystEngComm. 2009, 11 , 418-426. 5. Hasa, D.; Miniussi, E.; Jones, W. Cryst. Growth Des. 2016 , 16 , 4582–4588. 6. Chen, L.; Regan, M.; Mack, J. ACS Catal. 2016 , 6 , 868–872. 7. Nagapudi, K.; Umanzor, E. Y.; Masui, C. Int. J. Pharm. 2017 , 521 , 337-345. 8. Titi, H. M.; Do, J.-L.; Howarth, A. J.; Nagapudi, K.; Friščić, T. Chem. Sci. 2020 , 11 , 7578-7584.
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