Cinnoline chemistry. IX. 5‐, 6‐, 7‐ and 8‐halogen substituted 4‐mercaptocinnolines and related compounds

A series of 4‐mercaptocinnolines (4) monosubstituted with halogen in the benzenoid ring was obtained when the corresponding 4‐hydroxycinnolines were treated with phosphorus pentasulfide in either pyridine or toluene. On prolonged heating in either or the two solvents, the halogen atom in 6‐chloro‐ and 6‐bromo‐4‐hydroxycinnoline was simultaneously substituted with a mercapto group, thus yielding 4,6‐dimercaptocinnoline. Nucleophilic substitution of the halogen atom was also observed in the reaction of 6‐fluoro‐ and 7‐fluoro‐4‐hydroxycinnoline, while 8‐halo‐4‐hydroxycinnoline gave exclusively 8‐halo‐4‐mercapto‐cinnoline. From the reaction of 5‐halo‐4‐hydroxycinnoline the only identified products were 5‐halo‐4‐mercaptocinnolines. Previously unknown 4‐hydroxycinnolines were synthesized. 4‐Alkylmercaptocinnolines and 4,6‐dialkylmercaptocinnolines of pharmacological interest were prepared from the parent mercaptocinnoline or from the corresponding chlorocinnoline.