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

Abstract

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.

Construction of New Azo‐group Containing Polycyclic Imidazole Derivatives: Computational Mechanistic, Structural, and Fluorescence Studies

“…C(sp 3 )‐H activation ( TS10 ) optimized bond distance is 1.22 Å, which follows proton (H1) transformation to the IL O1 via 1.46 Å distance. A multicomponent reaction mechanism was calculated in our previous work …”

“…The 6–31++G(d,p) basis was used for sulfur in the catalyst (IL) based on our previous works . We chose M06 L functional because of the optimized and the experimentally obtained X‐ray structures are consistent with each other according to our previous work . Additionally, a comparative single point energy analysis for all stationary points of Figure was conducted with M06 L, M062‐X, and wB97XD functionals (See SI: page S61, Figure S2).…”

Computational mechanistic studies of the carbon–carbon double bond difunctionalization via epoxidation and subsequent aminolysis in vegetable oils

“…Since triplet spin state is determined as a ground state for NC, related Gibbs energies are included to the energy profile frequency (TOF) calculations [53]. As seen from the Gibbs energy profiles, the lowest energy TOF determining intermediate (IM2, TDI) appears after TS1 (the highest energetic TOF determining TS, TDTS), which directed us to use Equation (2) [25]:…”

“…But none of these works comparatively studied experimentally employed oxidizing agents. Computational tools were applied previously for the understanding of reaction mechanisms [20][21][22][23][24][25][26][27]. We chose a model reaction to reduce computational time for the present mechanistic studies: Instead of macromolecular triglyceride, but-2-ene was taken as the internal double bond carrier.…”

Flow Synthesis of 2‐[Methyl(pyridin‐2‐yl)amino]ethanol: An Experimental and Computational Study

“…In recent decades, one of the most employed calculation methods in computational chemistry is the density functional theory (DFT), which has been applied to the structural elucidation of conformational equilibrium of organic and inorganic compounds, orbital interactions, spectroscopic parameters, and molecular dynamics [6,7]. In addition, this method allows to show a variety of phenomena through breaking and formation of bonds arising from changes in the electronic states of the reactants [8], thus being able to corroborate the experimental results. The use of microreactors and computational chemistry can bring benefits to the chemical-pharmaceutical industry in drug development and production.…”