Reactivity of various halogenating agents toward different substrates in electrophilic substitution reactions: a computational study†

More and more halogenating agents have been identified in disinfection systems; however, quantifying their reactivity remains challenging. In this study, 18 electrophiles, including 11 halogenating agents (H), 4 halogenated amines (HA), and 3 sulfonylating/acylating (S/A) agents, as well as 12 substrates containing 5 C-reactive compounds (C-), 6 N-reactive amines (N-), and 1 O-reactive alcohol (O-) were chosen to explore their reactivity in electrophilic substitution reactions using the DFT method. The results indicated that the reactivity of electrophiles was highly sensitive to the hardness (energy gap E_LUMO–HOMO as a descriptor) of the substrate. Among the electrophiles, HA generally exhibited the lowest reactivity, except for NH₂Br with some substrates. For the soft C-substrates, the reactivity of H was higher than that of S/A; however, as the hardness of substrates increased, the reactivity of S/A surpassed that of some/all H for hard N- and O-substrates. Interestingly, alcohol, the hardest substrate tested in this study, shared the same reactivity order as phenolate, the softest substrate, in reactions with H, which was X–X′/OX′/OX >/≈ X–X > X–OH and HOI > HOBr > HOCl, but the rate constant k_est was lower by 7–17 orders of magnitude. However, the order was Cl- > Br- > I-agents for the medium aliphatic amine-N substrates. This explains the experimentally observed differences in halogenated product generation from various electrophiles. The results provide valuable insights into the reactivity of various electrophiles and substrates, providing a theoretical reference for choosing appropriate disinfectants based on the types of substrates present in water.