Nucleophilic aromatic substitutions on 4,5-dicyanopyridazine: Application of bis-nucleophiles

Unusual reactivity is shown by 4,5-dicyanopyridazine (DCP) as a heterocyclic electrophile at the C-4 carbon atom when interacting with nitrogen nucleophiles, leading to the displacement of a cyano group via a formal SNAr2 mechanism. In this study, suitable bis-nucleophiles were employed for the first time, enabling the straightforward and efficient synthesis of difunctionalized pyridazines and fused polycyclic pyridazines with good yields under mild reaction conditions. Thus, an aminopyrazole and an aminoisoxazole were converted into a pyrazolopyridopyridazine and an isoxazolopyridopyridazine, respectively, through domino processes when reacted with DCP. The reaction of DCP with benzamidine resulted in an aromatic addition reaction that formed a bicyclic piridazine with a spiro C-4 carbon, sacrificing the aromaticity of the pyridazine ring.