Statistical and theoretical studies of fluorophilicity

Linear free energy relation (LFER) models of the partition of 91 organic compounds between organic and fluorous solvents are presented. By reducing organic/fluorous partition to a sum of solvent–solute interaction terms we have developed accurate predictive models, with a standard deviation for prediction less than three times the estimated experimental error. Moreover, the physicochemical factors which affect a molecule’s fluorophilicity are identified: fluorine content, dispersion and hydrogen bond acidity factors are particularly important, with polarity, hydrogen bond basicity and size effects playing a much smaller role. The predictive ability of multiple linear regression is confirmed for several test sets, and factors affecting fluorophilicity for different classes of molecules discussed. Ab initio methods were used to calculate the stabilisation energies for different conformations of (F2)2 dimers. Correlation consistent basis sets at the MP2 level were used since split valence basis sets were found to be inadequate in their description of the system. The potential energy surface (PES) of the most stable conformer (L-shaped) was analysed and calculated stabilisation energies were used to successfully fit parameters for potential energy functions. A quadrupole term was added to the Buckingham function yielding an excellent fit.