A convenient and accurate method for predicting C-13 chemical shifts in organic molecules

摘要

The C-13 NMR shifts of a variety of organic compounds including pinanes and steroids were predicted using combined molecular mechanics (Pcmod 9.1/MMFF94) and ab initio GIAO (B3LYP/DFT,6-31G(d)) calculations. The accuracy of the ab initio calculations was no different when using the 6-31G(d) basis set than more complex basis sets but the calculations were much faster. The MM calculations for steroids took a few seconds and the Gaussian calculations ca. 45 minutes on a desktop computer. For the data set of alkanes, alkenes and alkynes the C-13 shifts were obtained from the GIAO isotropic shieldings (C-iso) by (a) empirically scaled shieldings (delta(c) = A - B.C-iso) and (b) separate references for sp(3), sp(2) and sp carbons (delta(c) = delta(ref) - C-iso). The second method gave better agreement and was used henceforth. For the data set of 34 alkanes, alkenes and aromatics with 96 shifts the mean absolute error (MAE) was excellent (0.90) ppm but the alkyne data set (7 compounds with 27 shifts) did not give as good agreement (MAE 1.7 ppm). For the more complex substituted compounds, pinanes and steroids the MAE 2 ppm but with large errors mainly from the C-X carbons (X = F, Cl, Br, O, = O). The agreement for fluorocyclohexane (axial and equatorial) was, apart from C-1 so good that the fluorine substituent effect is completely explained by this model. The calculations for the pinanes gave good agreement with two exceptions, C-6 in the cyclobutane ring and the C=C-CO carbon fragment. In both cases the use of different geometries (MM3 and 6-31G(d) res.) gave good results (apart from the CO carbon) suggesting that the errors are due to the molecular geometries in these strained molecules. In contrast for the seven steroids examined the MAE was 1.4 ppm and the assignments of the calculated and experimental shifts were almost identical. Thus this method could be very useful in assigning the C-13 spectra and determining the conformations of relatively large molecules.