Density Functional Theory/GIAO Studies of the ¹³C, ¹⁵N, and ¹H NMR Chemical Shifts in Aminopyrimidines and Aminobenzenes:  Relationships to Electron Densities and Amine Group Orientations

The dependence of the ¹³C, ¹⁵N, and ¹H isotropic NMR chemical shifts on amine substitution of aromatic ring systems are examined both experimentally and by DFT/GIAO (density functional theory/gauge including atomic orbitals) methods. There are large, monotonic decreases in the chemical shifts at odd-numbered (ortho and para) pyrimidine ring positions which do not occur at the even-numbered (ipso and meta) atoms as amine groups progressively replace hydrogens at the latter positions. This behavior parallels the computed 2p_z electron densities which for the pyrimidine series increase monotonically at N1, N3, and C5 but exhibit small changes at the C2, C4, and C6 positions. Identical trends are noted for the aminobenzenes. The ring atom chemical shifts and 2p_z electron densities at ortho and para (but not meta) positions are quite sensitive to the orientations of the amine groups which are pyramidalized as the result of balance between delocalization with the ring and the use of strongly directed sp³ orbitals at the nitrogen. The calculated results show that the barriers to amine group torsional and inversion motions are low, but averaging the chemical shifts over these appears to be relatively unimportant. Differences between the DFT and Hartree−Fock-based chemical shifts show that electron correlation effects monotonically increase with the number of NH₂ substituents.