Prediction of vicinal proton-proton coupling constants ³J _HH from density functional theory calculations

Vicinal coupling constants ³J_HH have been calculated at the optimized geometries for a series of selected molecules with the aim of developing a practical procedure for predicting this kind of coupling. Calculations of couplings and optimizations of molecular geometries have been carried out at the DFT/B3LYP level using a moderate sized basis set. When the Fermi contact contributions to ³J_HH calculated for 25 mono- and 23 1,1-di-substituted ethanes are multiplied by a factor of 0.904, the corresponding predicted couplings J^pre are in good agreement with the experimental J^exp couplings, with standard deviation σ of 0.10 Hz. When such a comparison is carried out for the remaining sets of molecules the σ deviation increases to 0.26 Hz for a dataset of 21 couplings from 11 monosubstituted cyclohexanes, to 0.19 Hz for a dataset of 40 couplings from 6 norbornane type molecules and to 0.25 Hz for a dataset of 54 couplings from 14 three-membered rings. For the complete dataset of 163 couplings the σ deviation amounts to 0.20 Hz. This figure is further reduced to 0.17 Hz by adding to the J^pre coupling a small correction given by the term -0.15cosφ, depending on the dihedral angle φ between the coupled protons. A larger σ deviation of 0.31 Hz was reported for the best empirically parameterized extended Karplus equation. DFT J^pre values could be further improved by more accurate calculations for the pertinent substituted ethane constituents of the molecule in question by applying a substituent effect model.