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

Abstract

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.

A Berzelius Reagent, Phosphorus Decasulfide (P4S10), in Organic Syntheses

“…Similar reaction of hydroxyl cinnolines 331 − 335 with P 4 S 10 in boiling pyridine, toluene, or quinoline yielded the corresponding thiols 336 − 343 (Scheme ) …”

“…334 Similar reaction of hydroxyl cinnolines 331-335 with P 4 S 10 in boiling pyridine, toluene, or quinoline yielded the corresponding thiols 336-343 (Scheme 90). 335 The usual product obtained on reaction of P 4 S 10 with alkylalcohols is dialkyldithiophosphoric acid, which forms at various temperatures and with various solvents, including pyridine, toluene, benzene, CS 2 , and dichloromethane (Table 15). Moreover, some reactions were conducted as neat (entries 1 and 4) and under microwave irradiation (entry 11).…”

Methods for the synthesis of cinnolines (review)

“…The formation of a cinnoline ring with the participation of arylhydrazones through the construction of a bond between the fourth carbon atom and the benzene ring can also be realized under the conditions of the Friedel-Crafts reaction. This approach was first described in 1956 by Barber and co-workers [48,49]. They realized the cyclization of the phenylhydrazone of mesoxalyl chloride catalyzed by titanium salts, as a result of which after alkaline hydrolysis they obtained 4-hydroxycinnoline-3-carboxylic acid (Scheme 11).…”