Thiol Chlorination with N-Chlorosuccinimide: HCl-Catalyzed Release of Molecular Chlorine and the Dichotomous Effects of Water

The kinetics of the conversion of thiophenols into sulfenyl chlorides using N-chlorosuccinimide (NCS) in dichloromethane have been investigated by in situ 1H NMR and stopped-flow UV–vis spectroscopy. The study reveals that a slow direct chlorination of the thiophenol by NCS initiates a more rapid but indirect process involving in situ generation of a disulfide and then its cleavage by transient Cl2. The latter is released from NCS by HCl and the switch in dominant pathway results in sigmoidal kinetics for the thiophenol consumption. The overall reaction rate can be attenuated by using an alkene to scavenge the sulfenyl chloride before it reacts with the thiophenol. The presence of water in the dichloromethane induces two distinct kinetic regimes, dependent on whether the water is below or above a critical concentration. The value of this critical concentration is dependent on the amount of HCl in the system. As the exogenous water is increased to the critical concentration, there is a proportionate acceleration of the HCl-mediated release of Cl2 from the NCS. At water concentrations above this, there is a progressive reduction in the rate of Cl2 release due to {H2O + nHCl} undergoing a change in speciation or physical phase. Alcohols, e.g., i-PrOH, efficiently catalyze the conversion of thiophenols into sulfenyl chlorides, with further oxidation retarded by trace amounts of disulfide, indicative of analogous HCl-catalyzed slow-release of Cl2. High reactant concentrations can lead to sufficient exothermicity to trigger an abrupt and vigorous release of gaseous HCl. Potential methods to mitigate against developing these hazardous conditions are also discussed.