Ionic Liquid Solvation versus Catalysis: Computational Insight from a Multisubstituted Imidazole Synthesis in [Et2NH2][HSO4]

The mechanisms of a tetrasubstituted imidazole [2-(2,4,5-tri-phenyl-1H-imidazol-1-yl)ethan-1-ol]synthesis from benzil, benzaldehyde, ammonium acetate, and ethanolamine in [Et2NH2] [HSO4] ionic liquid (IL) are studied computationally. The effects of the presence of the cationic and anionic components of the IL on transition states and intermediate structures, acting as a solvent versus as a catalyst, are determined. In IL-free medium, carbonyl hydroxylation when using a nucleophile (ammonia) proceeds with a Gibbs free energy (Delta G*) barrier of 49.4 kcal mol(-1). Cationic and anionic hydrogen-bond solute-solvent interactions with the IL decrease the barrier to 35.8 kcal mol(-1). [Et2NH2][HSO4] incorporation in the reaction changes the nature of the transition states and decreases the energy barriers dramatically, creating a catalytic effect. For example, carbonyl hydroxylation proceeds via two transition states, first proton donation to the carbonyl (Delta G * = 9.2 kcal mol(-1)) from [Et2NH2](+), and then deprotonation of ammonia (Delta G* = 14.3) via Et2NH. Likewise, incorporation of the anion component [HSO4](-) of the IL gives comparable activation energies along the same reaction route and the lowest transition state for the product formation step. We propose a dual catalytic IL effect for the mechanism of imidazole formation. The computations demonstrate a clear distinction between IL solvent effects on the reaction and IL catalysis.