Reactivity of various halogenating agents toward different substrates in electrophilic substitution reactions: a computational study†
Abstract
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 ELUMO–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 kest 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.