Global and local DFT-based reactivity descriptors are used to characterize phenolysis and benzenethiolysis reactions of methyl 2,4-dinitrophenyl carbonate, O-ethyl 2,4-dinitrophenyl thiolcarbonate, methyl 2,4-dinitrophenyl thionocarbonate and O-ethyl 2,4-dinitrophenyl dithiocarbonate. The conceptual framework to rationalize the trends observed in reaction rate constants and to explain the main reaction product encountered experimentally is provided by the Pearson’s HSAB principle. Molecular hardness of the reactant molecules indicate that the reactions are favored when hard–hard or soft–soft interactions are present. Local softness are found to be the most adequate descriptors to characterize local interactions that might be driving the phenolysis and benzenethiolysis reactions.