Molecular dynamics and cluster-continuum insights on bulk alcohols effects on SN2 reactions of potassium and cesium fluorides with alkyl halides

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Bulk alcohols like tert-butanol have been investigated as reaction medium for SN2 reactions, especially nucleophilic fluorination. Nevertheless, details of alkali metal salts in tert-butanol solution, as well as the transition state solvation, have not been investigated. This work presents a molecular dynamics study of pure tert-butanol and solution of KF in tert-butanol. The interaction and structure of the SN2 transition state in tert-butanol solution has also been investigated using both molecular dynamics and density functional theory calculations. In the last case, the transition state is solvated by a cluster of four tert-butanol molecules and by a dielectric continuum. The present study point out the KF and CsF salts form ion pairs in tert-butanol, and the strong interaction of hydroxyl groups of tert-butanol with both cation and anion, combined with low entropy for formation of cluster in solution, facilitates the solubilization of inorganic salts, although the solubility is predicted be low. The reaction of solubilized KF and CsF has low free energy of activation and the transition states involve participation of the tert-butanol molecules. This fact turns the CsF more reactive than KF. The free energy of activation for CsF reaction with ethyl bromide is predicted to be 28.4kcalmol−1, close to the experimental value of 28.9kcalmol−1 for a similar system.