Beyond the Solvent Effect: Theoretical Design of Nanostructured Environment for Controlling Ionic Reactions

Ion-molecule reactions have a substantial solvent effect. In some situations, the counter-ion can play an important role on the reaction kinetics, participating of the transition state. For aprotic solvents, some salts such as KF and CsF have low solubility. Thus, it is a challenge to activate the fluoride ion for nucleophilic substitution reaction. For example, even the use of crown ether to solubilize and activate KF can be limited, once the reaction requires a very long reaction time under reflux (1 week). In past decade, we have introduced a new catalytic concept based on selective solvation of the anionic transition state via hydrogen bonding. Using theoretical calculations, we have done first-principles design of new catalytic systems based on the combination of crown ether with alcohols and thioureas. Our research has indicated that this combination can be very effective to solubilize and activate KF for nucleophilic fluorination. Some designed catalytic systems are presented below and the catalytic combination of crown ether with bulky diol was confirmed experimentally. Several studies on this area will be discussed in this presentation.

1 - Dalessandro, E. V.; Pliego, J. R., Mol. Syst. Des. Eng. 2020, 5, 1513-1523

2 - Silva, S. L.; Valle, M. S.; Pliego, J. R., J. Org. Chem. 2020, 85, 15457–15465.

3 - Silva, S. L.; Valle, M. S.; Pliego, J. R., J. Mol. Liq. 2020, 319, 114211.