Nitrile oxide [3 + 2] cycloaddition: application to the synthesis of 6-substituted 3(2H)-pyridazinones and 6-substituted 4,5-dihydro-4-hydroxy-3(2H)-pyridazinones

An efficient method for the prepn. of 6-​substituted 3(2H)​-​pyridazinones and 6-​substituted 4,​5-​dihydro-​4-​hydroxy-​3(2H)​-​pyridazinones starting from 3,​5-​disubstituted 4,​5-​dihydroisoxazoles is described. N-​O bond cleavage of the isoxazoline ring promoted by molybdenum hexacarbonyl or by catalytic hydrogenation afforded the α-​hydroxy γ-​keto esters RCOCH2CH(OH)​CO2Et (I, R = Me, Bu, 2-​, 4-​pyridyl, 4-​HOC6H4) which were converted into 6-​substituted 4,​5-​dihydro-​4-​hydroxy-​3(2H)​-​pyridazinones for 6-​substituted 3(2H)​-​pyridazinones on treatment with hydrazine hydrate at room temp. or reflux in high yield starting from I. An intramol. version of this methodol. has been developed to prep. the known antiulcer tricyclic 5H-​[1]​-​benzopyrano[4,​3-​c]​pyridazin-​3(2H)​-​one.