DMF-Catalyzed Direct and Regioselective C-H Functionalization: Electrophilic/Nucleophilic 4-Halogenation of 3-Oxypyrazoles

A novel, straightforward, and highly regioselective 4-chlorination of 3-oxypyrazole derivatives in boiling thionyl chloride (SOCl2) in the presence of catalytic N,N-dimethylformamide (DMF) has been developed. This reaction likely proceeds through a DMF-catalyzed electrophilic/nucleophilic chlorination mechanism and involves electrophilic attack by SOCl2 and nucleophilic substitution by Cl- as the key steps. Based on this mechanism, the corresponding 4-bromination and 4-iodination of 3-oxypyrazoles have also been achieved in good yield by adding Br- and I-, respectively, to the reaction system. This halogenation method enables quick access to many original 4-halo-3-oxypyrazole series.