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-triphenyl-1 H-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 (ΔG^≠) 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 (ΔG^≠=9.2 kcal mol⁻¹) from [Et₂NH₂]⁺, and then deprotonation of ammonia (ΔG^≠=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.