A reinterpretation of the substituent effect on the amide barrier. An experimental and theoretical study

Recent theoretical work on amide systems has brought into question the appl ication of the concept of resonance. In particular, the role of the oxygen atom was questioned, since the calculations showed little change in its pro perties when the amide bond was rotated. This paper investigates, both expe rimentally and computationally, the effect of a substituent on the carbonyl carbon on the amide barrier, in order to test this view. The barriers to t he amide rotation in seven spiro-fused oxazolidines were measured by NMR, t o within 1 kJ mol(-1). A subset of three of them was modelled to the 6-31G* * level. For all three substituents the computed and measured barriers corr esponded to within 7 kJ mol(-1). The electron densities were analyzed using the Atoms in Molecules (AIM) theory. The AIM analysis revealed that the ox azolidines behaved similarly to formamide. The substituent effect was descr ibed in terms of the atomic populations and energies of the amide C, O, and N. A substituent on the carbonyl carbon caused electron redistributions be tween N and C, changing their basin attractive energies. Neither the popula tion nor the energy of oxygen changed significantly. When interactions outs ide the basin of interest were considered, the energy of C was seen to be m ore sensitive to changing the substituent than the energy of N. However, th e atomic parameters from the AIM analysis did not fully reflect the substit uent effects observed. For these molecules, the barrier includes contributi ons from several sources - there is no single, dominant contribution.