Critical Computational Evidence Regarding the Long-Standing Controversy over the Main Electrophilic Species in Hypochlorous Acid Solution

Abstract

Although hypochlorous acid (HOCl) solution has become a popular electrophilic reagent for industrial uses, the question of which molecule (HOCl or Cl2) undergoes electrophilic addition with olefins remains a controversial issue in some literature and textbooks, and this problem has been largely underexplored in theoretical studies. In this work, we computationally studied the electrophilic addition mechanism of olefins using three experimentally predicted effective electrophilic chlorinating agents, i.e., HOCl, Cl2, and Cl2O molecules. Our results demonstrate that Cl2 and Cl2O are the main electrophilic agents in HOCl solution, whereas the HOCl molecule cannot be the electrophile since the energy barrier when directly adding HOCl molecule to olefins is too high to overcome and the “anti-Markovnikov” regioselectivity for tri-substituted olefin is not consistent with experiments. Notably, the HOCl molecule prefers to form oxonium ion intermediate with a double bond, rather than the generally believed chlorium ion intermediate. This work could benefit mechanistic studies of critical biological and chemical processes with HOCl solution and may be used to update textbooks.

Dissecting the Crosstalk between Bisulfite and Hypochlorous Acid in the Reaction-Based Fluorescence Detection with Dicyanovinyl-Based Probes

“…The Michael addition is significantly retarded by the steric hindrance at the electrophilic carbon; thus, we can suppress interference from the nucleophilic addition of bisulfite by increasing the steric hindrance around the reaction site. On the other hand, the electrophilic addition of hypochlorous acid to electron-rich vinyl compounds will be favored . Therefore, to detect hypochlorous acid selectively from bisulfite in the reaction-based sensing scheme, it is necessary to increase the steric hindrance at the Michael addition site while maintaining or increasing the electron density of the vinyl unit.…”

“…Oil baths were used as the heating source. The 1 H and 13 C NMR spectra were measured in CDCl 3 using a Bruker AVANCE III FT-NMR spectrometer (600 MHz). The coupling constants (J value) are reported in Hertz.…”

“…1 H NMR (600 MHz, CDCl 3 , 298 K): δ 8.13 (s, 1H), 8.01 (dd, J = 9.0, 1.8 Hz, 1H), 7.87 (s, 1H), 7.75 (d, J = 9.6 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.15 (dd, J = 9.6, 2.4 Hz, 1H), 6.86 (d, J = 2.4 Hz, 1H), 3.77−3.73 (m, 8H), and 3.13 (s, 6H). 13 C{ 1 H} NMR (150 MHz, CDCl 3 , 298 K): δ 164. 7, 154.2, 150.9, 137.8, 133.9, 131.1, 127.3, 126.1, 126.1, 125.9, 117.8, 116.8, 105.8, 101.6, 67.1, and 40.8.…”

“…On the other hand, the electrophilic addition of hypochlorous acid to electron-rich vinyl compounds will be favored. 13 Therefore, to detect hypochlorous acid selectively from bisulfite in the reaction-based sensing scheme, it is necessary to increase the steric hindrance at the Michael addition site while maintaining or increasing the electron density of the vinyl unit. Note that other biological species are known to interfere little in detecting the two analytes using DCV-based probes.…”

Computational Investigations of Reaction Mechanisms and Transformation Products of Olefins with Hypochlorous Acid

“…1 Besides the chloronium-ion intermediate, an oxonium-ion intermediate in the reaction of HOCl with trans-1,2-dimethyl ethylene as demonstrated in Scheme 1b was also found using the density functional theory (DFT) method. 29 As shown in Scheme 1c, a carbon cation was also proposed to be produced before the chloronium-ion formation in the reaction of the lycopene model with HOCl. 30 For the initial intermediate of olefins reacting with HOCl, it is still unclear whether the chloronium ion is the only intermediate as accepted for all kinds and what relationship of above proposed intermediates.…”