Theoretical studies on proton transfer reaction of 3(5)-substituted pyrazoles

Abstract

The inter and intra molecular proton transfer reactions of a series of pyrazole derivatives have been studied by using density functional theory (DFT) and MP2 methods implementing 6-311++G(d,p) atomic basis set. The substituents have been selected to cover a wide range of electronic effects. Proton transfer process was studied for mechanisms including single proton transfer, double proton transfer and proton transfer assisted by a water or ammonia molecule. The results showed single proton transfer reactions for interconversion pyrazole derivatives need highest activation energies in the range of 45.7−51.59 and 49.4−53.96 kcal/mol at B3LYP and MP2 levels, respectively. It was found that for the 3-substituted pyrazoles, electron withdrawing groups form stronger dimers but in the 5-substituted tautomers electron donating groups form stronger hydrogen bond. The double proton transfer reactions between dimers were studied and transition states calculated. The ranges of activation energies were found to be 17.51−19.36 and 17.02−17.80 kcal/mol for the C→E and D→D reactions respectively. In addition, the activation energies for the proton transfer reaction assisted by water or ammonia molecules were found to be in the range of 26.62−31.78 and 17.25−22.46 kcal/mol, respectively, calculated at MP2/6-311++G(d,p) level of theory.

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

“…As for intermolecular interactions, the effect of the substituents was also shown to be quite relevant, since the hydrogen-bond strength in each tautomer was shown to differ according to the electronic character of the attached groups: electron donating groups stabilized 3-substituted dimers, while electron withdrawing ones favored self-associations of 5-substituted tautomers. Additionally, as stated previously in this review, energy barriers determined for intermolecular processes were shown to be lower than the intramolecular ones [43].…”

“…These conclusions were later corroborated by Chermahini et al, using the same type of study, through DFT B3LYP and also ab initio MP2 calculations [43]. Dealing with hybrid functionals, at the 6-311++G(d,p) level of theory, the authors reported that 3(5)-substituted pyrazoles detain preferential structures in behalf of the electronic features of substituents: electron donating groups sustain a C3 configuration, while electron withdrawing ones stabilize the system when occupying a C5 position.…”

“…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].…”

“…Figure 5 depicts the transition states for the two proposed manners of interaction with water molecules, the same being applicable to ammonia. From their study, the authors concluded that lower energetic barriers were achieved for the transition state (b) of Figure 5 and also that ammonia molecules stabilize the transition state to a greater degree than water [43]. A study by Oziminski followed, focusing on water-aided proton transfer.…”

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

“…In a very recent paper, the kinetics of proton transfer in a series of 3(5)-substituted pyrazoles was studied using MP2/6-311? ?G(d,p) level of theory [33].The barrier for unassisted proton transfer for unsubstituted pyrazole was determined to be 48.3 kcal/mol. It was found that the barrier was lowered to 29.2 kcal/mol by the assistance of 1 water molecule and to 22.5 kcal/mol by the assistance of 1 ammonia molecule.…”