Conformation of secondary amides.: A predictive algorithm that correlates DFT-calculated structures and experimental proton chemical shifts

The magnetic deshielding caused by the amido group on CON-CHalpha. protons of secondary amides can easily be correlated with DFT-based structures at the B3LY-P/6-31G* level of theory via a novel algorithm that refines previous models, such as the classical McConnell equation. The shift is given by delta = alpha + 2.16 cos(2)(alpha - 35)/d, where alpha denotes the virtual dihedral angle resulting from linking the carbonyl and the alpha-carbons and d is the distance (Angstrom) between the shifted proton and the carbonyl oxygen. Notably, in this equation a is a parameter that can be optimized for different solvents, namely, CDCl3, DMSO-d(6), and D2O. For the development of these correlations, the preferential conformation of amides is taken from the optimized structures in the gas phase obtained at the DFT level. The deshielding on anti and gauche protons in both rotamers of (Z)-acetamides and E/Z isomers of formamides has been evaluated. This methodology has proved to be highly reliable, allowing us to discard ab initio or DFT conformational arrangements when shifts calculated by the above-mentioned equation differ from the experimental values. Thus, the anti disposition between the CHalpha proton and the N-H bond appears to be the more stable conformation of simple amides. For amides bearing only one proton at Calpha, a local syn minimum can equally be characterized. The rotational barriers around the CON-alkyl bond along with the pyramidalization of the amido group have also been reassessed. As the conformation is taken away from anti or local syn minima, the nonplanarity of the amido group appears to increase.