A Tunable Heteroannulation Route to Fused Pyrazoles

Significance

2-Pyrazinyl and 3-pyridazinylketone arylhydrazones have been found to undergo ring-closure reaction under acid-catalyzed and thermal conditions to yield pyrazolo[3,4-b]pyrazines or pyrazolo[4,3-c]pyridazines. The reaction proceeds in adequate to good yields but its substrate scope was poorly studied. More emphasis was placed on the cyclization mechanism which was studied using quantum chemical calculations. The calculations suggest a pericyclic mechanism under thermal conditions and the pericyclicity is still favored under acidic conditions. The cyclization also proceeds under basic conditions for which the calculations suggest a pseudoelectrocyclization mechanism.