Chemometrical Analysis of Substituent Effects. XIII. Comparison of Substituent Effects on Dissociation and Chemical Shift in 13C NMR Spectra of Mono- and Disubstituted Benzoic Acids

Abstract

The 13C chemical shifts have been measured of the carboxyl carbon atoms for all the 2-, 3-, and 4-substituted benzoic acids with H, CH3, CH3O, F, Cl, Br, I, and NO2 substituents, as well as for all 3,4-, 3,5-, and 2,6-disubstituted benzoic acids with combinations of CH3, CH3O, Cl (or Br), NO2 substituents and for symmetrically 2,6-disubstituted derivatives with Et, EtO, PrO, i-PrO, and BuO substituents. The chemical shifts of carboxylic group carbon atoms of the 3- and 4-substituted derivatives show correlation only with the substituent constants σI. For the 2-substituted derivatives was found the dependence only on σI and on the υ constant describing steric effects (s = 0.122, R = 0.996, without the CH3 derivative which has a distinct anisotropic effect). The substituent effects on the carboxylic carbon chemical shift show additivity with 3,4-, 3,5-, and 2,6-substituents, and the 2,6-disubstituted derivatives show a linear synergic effect of substituents due obviously to the steric hindrance to resonance. Application of the principal component analysis to the data matrix involving all the combinations of mono- and disubstitution involving the above-mentioned substituents has proved an identical substituent effect from all the positions on the chemical shift described by one latent variable, steric effects and anisotropic behaviour of methyl at the 2 and 2,6 positions being predominantly described by the second latent variable (with the total explained variability of 99.5%). Comparison of substituent effects on the chemical shift of carboxylic carbon with that on the dissociation constant measured in the same solvent has confirmed the anisotropy due to ortho methyl group, the ortho halogen substituents in monosubstituted derivatives also having a different effect. The dependence of chemical shift on pKa was not very close for the derivatives studied (s = 1.005, R = 0.690). The inclusion of anisotropy of ortho alkyl group by means of an indicator variable improved the correlation (s = 0.533, R = 0.925), and omitting of 2-F, 2-Cl, 2-Br, and 2-I substituents gave a regression without deviating points (s = 0.352, R = 0.968).