Divergent Reactivity of N-Isocyanates with Primary and Secondary Amines: Access to Pyridazinones and Triazinones

Cascade reactions for the synthesis of 1,2,4-triazinones and 5-aminopyridazinones are reported using alpha-ketocarbazones as N-isocyanate precursors and exploiting the divergent reactivity observed with primary and secondary amines. Triazinones were formed with primary amines, likely through addition of the amine on the N-isocyanate, followed by cyclization (condensation) on the ketone. In contrast, such cyclization is impossible for secondary amines; this allows in situ formation of enamines, which, upon cyclization, generate 5-amino pyridazinones. This sequence further illustrates the versatility of N-isocyanates in heterocyclic synthesis and provides a rare example of carbon nucleophiles reacting with N-isocyanates.