Effect of heterosubstituent and ring puckering angle on linear and nonlinear properties of exo-insaturated four-membered heterocycles, Y=CCH₂CH₂X: a comparative ab initio, DFT and semi-empirical study

Abstract

The influence of heterosubstituent and ring puckering angle (ϕ) on electronic properties (μ, α, β and γ ) of 16 four-membered heterocycles (1-16) were demonstrated theoretically using ab initio (HF and MP2), density functional theory (DFT) (PBE1PBE, SVWN5 and B3LYP) and semi-empirical (PM6 and PM3) treatments. Comparing the DFT and ab initio methods, these showed a similar description of electric dipole moment (μ) and polarisability (α) for each one of the studied heterocycles, with small differences in the prediction of α. The calculated hyperpolarisabilities (β and γ ) are very sensitive to the quality of level theory, especially when the heterocycles contain phosphorus and sulphur. On the other hand, comparing with the rest of methods used, the semi-empirical calculations show significant deviations in the prediction of the different properties, and only are in agreement with the calculations of μ for the heterocycles that do not contain phosphorus or sulphur. In general, β and γ are more sensitive to the molecular geometry than μ and α. The dipole moment is determined by the heteroatom (X) within the ring, where the oxetanes and thietanes exhibit a minimum value of μ at planar conformations, while the azetidines and phosphetanes at axial conformations. All heterocycles show a minimum value of α at planar conformation, and their largest values are associated to conformations highly puckered. β exhibits an implicit relationship with the C = Y bond according to the conformational states. In addition, the X and Y heterosubstituents affect significantly the values of α, β and γ , observing the largest values for the phosphorus-and sulphur-containing heterocycles. Finally, considering the values obtained for α, β and γ , the studied heterocycles can represent an interesting unit for the design of new promising push-pull systems as donor or acceptor group.

Tautomerism and Rotamerism of Favipiravir and Halogenated Analogues in Solution and in the Solid State

“…To obtain more information about the carboxamide rotamerism, a conformational analysis was performed on 6-fluoro-3-hydroxy-2-pyrazinecarboxamide 1a as the platform model. The conformational analysis for the enol tautomer was focused on structures having a rotating hydroxyl moiety with a “cisoide” (Figure A) or “transoide” carboxamide, whereas the keto tautomer was focused on structures having only a rotating carboxamide moiety (Figure C). − Within the enol tautomer, there are four preferential conformational forms: E_A , E_B , E_C , and E_D (Figure D). Among them, enol tautomer E_A (“cisoide” carboxamide) was identified as the most stable enolic conformer, followed by conformer E_C (“transoide” carboxamide) ( ΔE = 2.0 kcal/mol) and least stable conformers E_B ( ΔE = 5.9 kcal/mol) and E_D ( ΔE = 5.9 kcal/mol).…”