Dual Role of Quinoxalin-2-one-3-carbonitriles in the Synthesis of 2-(Benzimidazol-2-yl)perimidine and -Quinazoline Derivatives

Abstract Quinoxalin-2-one-3-carbonitriles have proven to be attractive building blocks for biologically active compounds, such as biheterocyclic systems with a benzimidazole moiety. Herein, we describe the acid-catalyzed Mamedov rearrangement of quinoxalin-2-one-3-carbonitriles when exposed to 1,8-naphthalenediamine that provides a direct synthetic approach to 2-(benzimidazol-2-yl)perimidines, where quinoxalin-2-one-3-carbonitriles play dual role furnishing both the C2 carbon atom of the newly formed perimidine ring and also the benzimidazole moiety. The rearrangement occurs via an ANRORC-type mechanism involving spiro derivatives of quinoxalinone generated in situ. This method gave various 2-(benzimidazol-2-yl)perimidines in 48–89% yields. The utility of this methodology is further demonstrated in the synthesis of new heterocyclic systems, namely 2-(1H-imidazo[4,5-b]pyridin-2-yl)-1H-perimidine and 2-(benzimidazol-2-yl)quinazoline scaffolds.