Scalable Synthesis of the Shelf-Stable Radical Difluoromethylthiolation Reagent S-(Difluoromethyl)benzenesulfonothioate PhSO2SCF2H

A procedure for the convenient preparation of an efficientradicaldifluoromethylthiolation reagent, namely, S-(difluoromethyl)-benzenesulfonothioate(PhSO2SCF2H), was reported. The reagent wassynthesized on an approximately 500 g scale in two steps from cheapcommodity sodium benzene sulfinate, benzyl mercaptan, and HCF2Cl. The key step of this protocol is to control the amountof chlorine and the reaction temperatures for the generation of keyintermediate [HCF2SCl]. Differential scanning calorimetry(DSC) was carried out to demonstrate the stability of PhSO2SCF2H. Furthermore, gram-scale reaction of PhSO2SCF2H with electron-rich aromatic (hetero)-hydrocarbons,alkyl carboxylic acids, and olefins was demonstrated.

Automated summary

A convenient method for the preparation of the efficient radical difluoromethylthiolation reagent PhSO2SCF2H was reported. The reagent was synthesized on a scale of approximately 500 g from cheap commodity sodium benzene sulfinate, benzyl mercaptan, and HCF2Cl in two steps. The key step of this method involves controlling the amount of chlorine and reaction temperatures to generate the key intermediate [HCF2SCl]. The stability of PhSO2SCF2H was confirmed by differential scanning calorimetry (DSC). Additionally, gram-scale reactions of PhSO2SCF2H with electron-rich aromatic (hetero)-hydrocarbons, alkyl carboxylic acids, and olefins were demonstrated.