On the reaction of phenacylmalononitrile with hydrazines: A new route to pyrazolo[3,4-c]pyridazine, isoxazolo[5,4-c]pyridazine and pyrimido[4,5-c]pyridazine

The reaction of arylmalononitiles 1a,b with hydrazine hydrate at room temperature has afforded 3-oxo-6-aryl-2,3,4,5-tetrahydropyridazine-4-carbonitrile 3a,b as the sole isolable product. These 3-oxopyridazin-4-carbonitriles underwent aromatization to 3-oxo-6-phenylpyridazine-4-carbonitrile 4 on attempted coupling with benzene diazonium chloride. Compound 3a reacted with hydrazine hydrate as well as urea to yield pyrazolo[3,4-c]pyridazine 5 and pyrimido[4,5-c]pyridazine 6. On the other hand, amidoximes 7a,b were isolated from reaction of 3a,b with hydroxylamine hydrochloride. Amidoximes 7a could be cyclized successfully into 5-phenylisoxazolo[5,4-c]pyridazin-3-amine 8 while 7b could not be cyclized on our hand.