Hybrid-Density Functional Theory, MO Study, and NBO Interpretation of Conformational Behaviors of 2-Halo-1,3-Dioxanes and Their Dithiane and Diselenane Analogs

Abstract

The impacts of the endo- and exo-anomeric effects (endo-AE and exo-AE), electrostatic interactions, and steric repulsions on the conformational behaviors of 2-fluoro-1,3-dioxane, -dithiane, -diselenane (1–3), 2-chloro-1,3-dioxane, -dithiane, -diselenane (4–6), and 2-bromo-1,3-dioxane, -dithiane, -diselenane (7–9) have been analyzed by means of natural bond orbital (NBO) interpretation, hybrid density functional theory (B3LYP/6–311+G**), and ab initio molecular orbital (HF/6–311+G**) based methods. Both methods showed the axial preference for compounds 1–9. The calculated Gibbs free energy difference (Geq–Gax) values (i.e.ΔGeq−ax) between the axial and equatorial conformations increases from compound 1 to compound 2 but decreases from compound 2 to compound 3. Contrary to the trend observed for compounds 1–3, the calculated ΔGeq−ax values decrease from compound 4 to compound 6 and from compound 7 to compound 9. Similar trends were also observed for the corresponding calculated AE values. On the contrary, the calculated differences between the dipole moment values of the axial and equatorial conformations, Δ(μeq−μax), cannot explain the variation of the calculated ΔG eq−ax for compounds 1–9. Consequently, the electrostatic model fails to account for the axial preferences in compounds 1–9. There is a conflict between the AE associated with electron delocalization and the steric effect impacts on the conformational behavior of compounds 1–9.