Examining Ionic Liquid Effects on Mononuclear Rearrangement of Heterocycles Using QM/MM Simulations

Abstract

The mononuclear rearrangement of heterocycles (MRH) reaction of the Z-phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole into 4-benzoylamino-2,5-diphenyl-1,2,3-triazole derives a sizable rate enhancement in the 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF] ionic liquid as compared to the hexafluorophosphate-based [BMIM][PF] and conventional organic solvents. However, the origin of the rate difference between [BMIM][BF] and [BMIM][PF] has proven difficult to rationalize as no experimental trend relates the physical properties of the solvents, e.g., polarity and viscosity, to the rates of reaction. QM/MM calculations in combination with free-energy perturbation theory and Monte Carlo sampling have been carried out for the MRH reaction to elucidate the disparities in rates when using ionic liquids, methanol, and acetonitrile. Activation barriers and solute-solvent interactions have been computed for both an uncatalyzed and a specific base-catalyzed mechanism. Energetic and structural analyses determined that favorable π-π interactions between the BMIM cation, the substrate phenyl rings, and the bicyclic quasi-aromatic 10π oxadiazole/triazole transition state region imposed a pre-ordered geometric arrangement that enhanced the rate of reaction. An ionic liquid clathrate formation enforced a coplanar orientation of the phenyl rings that maximized the electronic effects exerted on the reaction route. In addition, site-specific electrostatic stabilization between the ions and the MRH substrate was more prevalent in [BMIM][BF] as compared to [BMIM][PF].

Solvatochromic Absorbance and Fluorescence Probe Behavior within Ionic Liquid + γ-Butyrolactone Mixture

“…All the calculations to study the direction of binding of [bmim]­[BF 4 ] and GBL were obtained through a gradient-corrected DFT (density functional theory) method with the M06-2X/6-311**G (d,p) level of theory. − Gaussian 09 program was used to perform the density functional computational studies. The optimization of [bmim]­[BF 4 ], GBL, and different investigated structures was also obtained using the B3LYP/6-311**G basis set (Becke’s three-parameter hybrid exchange function with Pople basis set). , The electrostatic potential map (MEP) and HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) gaps were calculated by using the TD-DFT B3LYP/6-31**G method.…”

Molecular interactions between 1-butyl-3-methylimidazolium tetrafluoroborate and model naphthenic acids: A DFT study

“…The density functional computations were performed by using the Gaussian 09 program package [20]. Many theoretical studies on ILs were carried out by using M06-2X/6-311++g(d,p) level of theory [21][22][23][24][25] [26,27]. The coulomb-attenuating method CAM-B3LYP, which considers long-range interactions, was used in combination with 6-311++G(d,p) basis set to perform HOMO-LUMO overlap integral analysis [28].…”

Ionic liquids: “normal” solvents or nanostructured fluids?

“…Interestingly, polarity-based parameters failed to account for the reactivity observed, whereas the trend of the yields was explained considering the structural organization of the solvent with higher yields found in more extensively aggregated ILs. The rate-enhancing effect of the ordered structure of IL received further support from QM/MM calculations with free energy perturbation theory, 77 where the formation of an IL clathrate, by means of π-π stacking interactions, enforces a coplanar arrangement of the phenyl rings. Notably, a similar favourable organizing effect was also revealed by the same calculation methods for a different reaction such as nucleophilic aromatic substitution.…”