Conformational behaviors of 2-halo-1,2,4,5-tetrahydrobenzo[d]oxepines. A hybrid-density functional theory study and natural bond orbital interpretations

Hybrid-density functional theory (hybrid-DFT: B3LYP/6-311+G**) based methods and natural bond orbital (NBO) interpretation have been used to examine the impacts of the hyperconjugative, electrostatic and steric effects on the conformational behaviors of 2-fluoro-1,2,4,5-tetrahydrobenzo[d]oxepine (1), 2-chloro-1,2,4,5-tetrahydrobenzo[d]oxepine (2) and 2-bromo-1,2,4,5-tetrahydrobenzo[d]oxepine (3). B3LYP/6-311+G** results showed that the axial conformations of compounds 1-3 are more stable than their corresponding equatorial conformations and the axial conformation stability, compared to its corresponding equatorial conformation, increases from compounds 1→3. Based on the results obtained from the NBO analysis, there are significant anomeric effects associated with the electron delocalization for compounds 1-3. The endo-anomeric effect associated with LP(1)O(3)→σ*(C2-X) and LP(2)O(3)→σ*(C2-X) electron delocalizations increases from the axial conformation of compound 1 to compound 2 but decreases from compound 2 to compound 3. The exo-anomeric effect decreases from compounds 1→3. The anomeric effect [i.e. ∑(endo-anomeric effect+exo-anomeric effect)(eq)-∑(endo-anomeric effect+exo-anomeric effect)ax] increases from compounds 1→3. Dipole moments of the equatorial conformations of compounds 1-3 are greater than those of their corresponding axial conformations and dipole moment difference between the axial and equatorial conformations [Δ(μeq - μax)] decreases from compounds 1→3. Therefore, the anomeric effect associated with the electron delocalizations explain the conformational preferences in compounds 1-3 but the electrostatic model associated with the dipole-dipole interactions fails to account the conformational preferences in compounds 1-3. The correlations between the anomeric effect, electrostatic model, ΔGeq-ax, bond orders, dipole-dipole interactions, structural parameters and conformational behaviors of compounds 1-3 have been investigated.

Conformational behaviors of 2-halo-1,2,4,5-tetrahydrobenzo[d]oxepines. A hybrid-density functional theory study and natural bond orbital interpretations Keywords:

Anomeric effects , Stereoelectronic interactions , molecular modeling , Ab initio , 2-Halo-1 , 2 , 4 , 5-tetrahydrobenzo[d]oxepines