Effect of Electronegative Substituents and Angular Dependence on the Heteronuclear Spin-Spin Coupling Constant 3JC-H: An Empirical Prediction Equation Derived by Density Functional Theory Calculations

A general carbon-proton vicinal coupling constant (3JC-H) prediction equation has been empirically derived by a coupling constant database of 2157 3JC-H calculations (at the hybridDFTMPW1PW91/ 6-31G(d,p) level). The equation includes the electronegativity effect of the substituents attached to the 13C-C-C-1Hfragment and the dihedral (Φ) dependence of the heteronuclear spin-coupling.Aset of butane and pentane models were built, systematically varying both theΦtorsion angle in 30 steps and the substitution pattern with several electronegative substituents (Br, NH2, F, Cl, SH, OH) in order to obtain the coupling constant database. The here reported 3JC-H equation is a quantitative prediction tool, particularly useful as a support in the analysis of NMR data for the structural elucidation of organic compounds characterized by specific substitution patterns. To confirm the accuracy of our equation in the prediction of the experimental 3JC-H couplings, we tested the equation, comparing 114 experimental 3JC-H values obtained from29 polysubstituded benchmark organic compounds with the predicted data. In addition, a set of 3JC-H coupling bidimensional Karplus-type curves correlating the calculated 3JC-H values to the specific dihedral angle for every substitution pattern considered were built in order to evaluate the magnitude of the electronegativity effect.