Theoretical studies of the formation of quaternary pyridinium mesylates

Abstract The pathway of the reaction between suitable mesylate derivatives and trimethylamine by which quaternary ammonium salts are formed according to the S N 2 mechanism was investigated. All calculations were performed at the B3LYP/6-31 + G ** level; activation barriers were also calculated at the MPW1K/6-31 + G ** level. All the structures were fully optimized in the gas phase, whereas single point calculations were done using the Polarizable Continuum Model (PCM) in three solvents: chloroform, ethanol and water. In all four cases studied, the reactions proceed via an initial reactant complex, followed by a transition state leading to an ion pair. In the reaction of methyl mesylate C 3 symmetry an ion pair is formed. The stabilizing exo -anomeric effect observed in compound 4 is lost when the reactant complex is formed. It is shown that the B3LYP/6-31 + G ** activation barrier increases when a hydrogen atom in the methyl group is replaced by a tetrahydrofuran ring. A certain differentiation of barriers relative to the bifurcation occurring at a site more distant from the reaction centre (γ carbon) is observed. MPW1K/6-31 + G ** level calculations show that activation barriers are at least 4 kcal mol −1 higher than those from B3LYP/6-31 + G ** . Results from the gas phase, from both the B3LYP and the MPW1K methods, indicate that compound 3 should be the least reactive. In the reaction of methyl mesylate with trimethylamine, transfer from the gas phase to the aqueous solution causes the barrier to decrease by more than 10 kcal mol −1 . A decrease in the energy barrier is also observed in the case of the other compounds, though to a considerably smaller degree.