Ionic Liquid Solvation versus Catalysis: Computational Insight from a Multisubstituted Imidazole Synthesis in [Et(2)NH(2)][HSO(4)]

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 [Et(2)NH(2)][HSO(4)] 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). [Et(2)NH(2)][HSO(4)] 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 [Et(2)NH(2)](+), and then deprotonation of ammonia (ΔG (≠)=14.3) via Et(2)NH. Likewise, incorporation of the anion component [HSO(4)](−) 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.