Reactivity and stability of ion pairs, dimers and tetramers versus solvent polarity: SNAr fluorination of 2-bromobenzonitrile with tetramethylammonium fluoride

Abstract

Anion–molecule reactions have a substantial solvent effect, which decreases with the solvent polarity. However, less solvation leads to the formation of ion pairs and higher aggregates that are usually less reactive. Consequently, theoretical determination of the best solvent for the reaction needs to consider all the species in equilibrium. In this report, we have investigated the wide range of solvent polarity in the SNAr reaction of the tetramethylammonium fluoride (TMAF) with 2-bromobenzonitrile, as well as the formation of ion pairs, dimers and tetramers using molecular dynamics and density functional calculations with continuum solvation. Five solvents were considered: methanol, dimethylformamide, pyridine, tetrahydrofuran and benzene. The TMAF exists predominantly as free ions in methanol, as ion pairs in dimethylformamide and pyridine, and as tetramers in tetrahydrofuran and benzene. The reaction takes place through free ions in methanol, ion pairs in dimethylformamide, pyridine and tetrahydrofuran, and via dimer in benzene. The calculations suggest that dimethylformamide and pyridine are the best solvents for this reaction.