Synthesis of Azuleno[2,1-<i>b</i>]quinolones and Quinolines via Brønsted Acid-Catalyzed Cyclization of 2-Arylaminoazulenes

Abstract

Quinolone and quinoline derivatives are frequently found as substructures in pharmaceutically active compounds. In this paper, we describe a procedure for the synthesis of azuleno[2,1-b]quinolones and quinolines from 2-arylaminoazulene derivatives, which are readily prepared via the aromatic nucleophilic substitution reaction of a 2-chloroazulene derivative with several arylamines. The synthesis of azuleno[2,1-b]quinolones was established by the Brønsted acid-catalyzed intramolecular cyclization of 2-arylaminoazulene derivatives bearing two ester groups at the five-membered ring. The halogenative aromatization of azuleno[2,1-b]quinolones with POCl3 yielded azuleno[2,1-b]quinolines with a chlorine substituent at the pyridine moiety. The aromatic nucleophilic substitution reaction of azuleno[2,1-b]quinolines bearing chlorine substituent with secondary amines was also investigated to afford the aminoquinoline derivatives. These synthetic methodologies reported in this paper should be valuable in the development of new pharmaceuticals based on the azulene skeleton.

Keywords

• azulene
• quinolone
• quinoline
• cyclization
• aromatic nucleophilic substitution