The kinetics of water-assisted tautomeric 1,2-proton transfer in azoles: a computational approach

Abstract

A complete set of azoles undergoing 1,2-proton transfer, consisting of pyrazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole and pentazole, was computationally investigated regarding proton transfer mechanism in gas phase and water solution. Complexes of one azole molecule with 1-4 water molecules were employed to facilitate the proton transfer by lowering the activation energy, which for the isolated azole molecule is prohibitively large. The calculations were performed at the MP2/aug-cc-pVDZ and B3LYP/6-311??G(d,p) levels of theory which showed very good concordance. It follows that in the most probable transition state one azole molecule is accompanied by two water molecules. The activation barrier in water solution modelled by PCM method was lowered to 18.8 kcal/mol in the case of pyrazole and more for azoles containing more nitrogen atoms in the ring, reaching 6.8 kcal/mol in the case of pentazole. The analysis of the IRC reaction paths showed that proton transfer in the gas phase has more synchronous character and in the water solution is rather stepwise. It also follows from the analysis of bond lengths in the transition state that in the case of pyrazole the transition state is more cation-like and for other azoles, especially pentazole, is more anion-like. In the water environment, the initial step of proton transfer is moving the proton from azole to the water cluster in all cases except pyrazole, where the proton moves first from the water cluster to the azole molecule.

Revisiting the Structure and Chemistry of 3(5)-Substituted Pyrazoles

“…It was shown by Alkorta et al that the proton exchange in pyrazoles is an intermolecular process rather than an intramolecular one, since the energy barrier determined for the intramolecular process displays values surrounding 50 kcal/mol, while the observed values for the intermolecular counterpart do not surpass the range of 10-14 kcal/mol [54]. The information available indicates that protons migrate either with the help of third parties, such as solvent molecules, as for example water molecules were shown to reduce the activation energies when attached to pyrazole, both in the gas-phase and in liquid environment [44], or of other pyrazole molecules, in self-assembled complexes. These contributions will be discussed throughout this manuscript.…”

“…Pyrazole-based self-aggregates in the gas-phase have been detected by Infrared (IR) spectroscopy, for the parent pyrazole and for 3,5-dimethylpyrazole, as an equilibrium between monomers, dimers and trimmers [38]. In addition, several theoretical studies were performed regarding intermolecular interactions in pyrazoles, leading to proton transfers in the gas phase [38,43,44].…”

“…Since pyrazoles were shown to form cationic transition states, the first species to donate the proton was found to be a water molecule. When comparing the two physical states, Oziminski suggested more synchronous exchanges in the gas phase than in solution [44].…”

“…Gas phase MP2 optimized transition states for 1, 2-proton transfer in complexes of pyrazole with (a) one; (b) two; (c) three and (d) four water molecules obtained by Oziminski[44].…”

Solvent and Substituent Effects on the Phosphine + CO2 Reaction

“…In the field of solvent effects there are specific and bulky effects. The specific effects are due to weak interactions, mainly hydrogen bonds, which are theoretically studied building up supramolecules, for instance, proton transfer in pyrazoles being assisted by two linked water molecules [1][2][3]. The general solvent effects consider the solvent as bulk and are studied empirically using solvent scales (Kamlet et al [4], Reichardt [5], Abraham [6], Catalán [7]), as well as theoretically using the polarizable continuum model, PCM (Tomasi et al [8]), the conductor-like screening model, COSMO (Orozco and Luque [9]), and Density Functional Solvation Model, DGSOL (Zhu et al [10]).…”