Enhancing and modulating the intrinsic acidity of imidazole and pyrazole through beryllium bonds

Abstract

The structure and electronic properties of the complexes formed by the interaction of imidazole and pyrazole with different BeXH(BeX2) (X = H, Me, F, Cl) derivatives have been investigated via B3LYP/6-311+G(3df,2p)//B3LYP/6-31+G(d,p) calculations. The formation of these azole:BeXH(BeX2) complexes is accompanied by a dramatic enhancement of the intrinsic acidity of the azole, as the deprotonated azole is much more stable after the aforementioned interaction. Most importantly, the increase in acidity is so large that the azole:BeXH or azole:BeX2 complexes behave as NH acids, which are stronger than typical oxyacids such as phosphoric acid and oxalic acid. Interestingly, the increase in acidity can be tuned through appropriate selection of the substituents attached to the Be atom, permitting us to modulate the electron-accepting ability of the BeXH or BeX2 molecule.

Enhancement of Thermodynamic Gas‐Phase Acidity and Basicity of Water by Means of Secondary Interactions

“…The reason behind this huge effect on the water acidity relies on the large binding energy differences between neutral and charged complexes. Previous works,,,,, have shown precisely that this binding enthalpy difference is related to the acidity enhancement through a thermodynamic cycle analogous to the one shown in Scheme .…”

“…It is well‐known that in molecular clusters linked by hydrogen bonds, from dimers onwards, the thermodynamic acid‐base properties of the terminal monomers are substantially modified, as for instance in (HCN) n and (HNC) n . We have reported the possibility of modulating the acidity of imidazoles and pyrazoles by means of beryllium bonds; the huge acidity increases produced by alkaline‐earth bonds; the large proton affinity (PA) enhancements triggered by non‐covalent interactions; and the changes on the acidity and basicity of disiloxane due to the formation of complexes with Lewis acids and Lewis bases …”

Some Interesting Features of Non-Covalent Interactions

“…36 Several examples of this kind were studied in detail by our group in recent years. [37][38][39][40][41] As a general rule, it has been observed that when a given compound forms a beryllium bond, the conjugated base becomes a much better electron donor than the acid from which it comes as compared with the same acid-base pair in absence of beryllium bonds, resulting in an acidity enhancement triggered by the beryllium bond. This acidity enhancement is the consequence of the significant amount of charge transferred from the Lewis base towards the available empty orbitals of the beryllium compound, accompanied, as explained in previous sections, by the corresponding deformation mainly of the BeX 2 subunit.…”

On the Importance of π‐Hole Beryllium Bonds: Theoretical Study and Biological Implications

“…Also of note is the work carried out by Marín‐Luna and co‐workers, who studied the effect of beryllium bonds on the tautomerism of two DNA bases, 9‐methylguanine and 1‐methylcytosine. Finally, a series of studies devoted to analysis of the interplay between beryllium bonds and other noncovalent forces should also be mentioned, highlighting the ability of beryllium bonds to act as efficient noncovalent regulators with beautiful and intelligent applications in fields such as molecular recognition and solid‐state chemistry.…”