Regioselective Transition‐Metal‐Free Synthesis of Diverse Benzothiazoles by Thermally Induced Cyclization of ortho‐Halobenzanilides

The highly regioselective and efficient synthesis of diverse substituted‐benzothiazoles, including heterocyclic units and amino groups, was achieved in moderate to high yields from ortho‐bromothiobenzanilides, ortho‐bromoarylthioureas, ortho‐bromobenzanilides, and ortho‐dibromobenzanilides, regardless of the electron density and substituted positions, via the prevalent carbon‐sulfur bond formation by thermally induced intramolecular cyclization reaction without using any metal sources or other additives. Polysubstituted‐benzothiazoles, particularly 2,4‐, 2,6‐disubstituted, and 2,4,6‐trisubstituted benzothiazoles, could be efficiently synthesized by a facile cascade reaction from appropriate ortho‐bromobenzanilides under general thiolation conditions. This benign reaction represents a straightforward and practical approach toward diverse substituted‐benzothiazoles. In addition, the remaining bromine substituent of the resulting products was further utilized as a functional handle for the additional diversification and exploited as a complementary solution for the adjustment of harsh reaction condition. This methodology not only allows for the elaboration of benzothiazole molecules, but also provides a new valuable synthetic tool for a range of pharmaceutical applications. From these methodologies, the electron density on the sulfur atom would be increased under thermal conditions regardless of the electronic environmental influence of the primary ring system and have its nucleophile character, which naturally allow to the formation of benzothioazoles. Therefore, access to diverse benzothiazoles by thermally induced intramolecular cyclization from either o‐halothiobenzanilides or o‐halobenzanilides via discriminative reaction routes could compensate for existing synthesis methods and make a simplified overall reaction process.