ANRORC type rearrangement/intermolecular cyclocondensation cascade of 5,6-dicyano-3-(2-oxo-2-ethyl)pyrazin-2(1H)-ones with hydrazine hydrate for the synthesis of 2-(pyrazol-3-yl)imidazo[4,5-d]pyridazines

Abstract

A novel H₂SO₄-catalyzed ANRORC-type rearrangement of pyrazinones to imidazoles proceeding through pyridazino[d]annulation with simultaneous introduction of a pyrazole ring at position 2 of the imidazole system has been developed, which offers efficient and expedited access to new biheterocyclic systems – 2-(pyrazol-3-ul)imidazoles and 2-(pyrazol-3-yl)imidazo[4,5-d]pyridazines. Diverse bi-N-heterocyclic systems with the imidazo[4,5-d]pyridazine-4,7-diamine moiety could be obtained in excellent yield when 5,6-dicyano-3-(2-oxo-2-ethyl)pyrazin-2(1H)-ones interact with hydrazines via the selective spiro-formation in a tandem ring-opening/ring-closing process, which allowed the simultaneous construction of five new C–N bonds. This new method is compatible with an array of functional groups, proceeds under mild reaction conditions with the involvement of commercially available reagents. Control experiments and DFT studies elucidate the detailed reaction mechanism.