Relative rates of addition of carbanions to substituted nitroarenes: can quantum chemical calculations give meaningful predictions?

Abstract

Computational description and kinetic properties based on density functional theory methods of the key step of the addition reaction between a model nucleophile and nitroaromatic ring in positions occupied by hydrogen are presented. A wide series of DFT functionals (PBE0, B3LYP, ωB97XD, M062X, PBE1PBE-D3, B3LYP-D3 and APFD) was used to track the influence of functional groups in nitroaromatic rings on reaction activation barriers. The comparison of experimentally determined relative rates of nucleophilic addition and their calculated thermodynamic counterparts at various positions in a series of ortho-, meta- and para-substituted nitroarenes are provided. It was shown that different DFT methods provide a good correlation between computed thermodynamic parameters and logarithms of experimental relative reaction rates. In addition, presented results show that DFT computations can be used for reliable prediction of relative reaction rates of vicarious nucleophilic substitution (VNS)-type of reactions. This work provides a valuable tool in the form of structure–thermodynamic property correlation data that can be used in the synthesis design process or QSAR type of analysis, where explicit trends are often required.