Synthesis of Some New 4,5-dihydro-6-(4-methoxy-3-methylphenyl)-3(2H)pyridazinone Derivatives

The present study describes the synthesis of 4,5-dihydro-6-(4-methoxy-3-methylphenyl)-3(2H)-pyridazinone derivatives. The synthesis of the first target compound, 4,5-dihydro-6-(4-methoxy-3-methylphenyl)-3(2H)-pyridazinone (1), was achieved by Friedel-Crafts acylation of o-cresyl methyl ether with succinic anhydride and subsequent cyclization of the intermediary g-keto acid with hydrazine hydrate. Condensation of compound 1 with aromatic aldehydes in the presence of sodium ethoxide affords the corresponding 4-substituted benzyl pyridazinones (3a-d). The dihydropyridazinone 1 underwent dehydrogenation upon treatment with bromine/acetic acid mixture to give (4). Pyridazine (5) has been synthesized upon the reaction of pyridazinone (1) with 1,3-diphenyl-2-propen-1-one under the Michael addition reaction. N-dialkylaminomethyl derivatives 6a-b have been obtained from the reaction of pyridazinone 1 with formaldehyde and secondary amine, whereas reaction of 1 with formaldehyde gives N-hydroxymethyl derivative (7). This study also includes the synthesis of the 3-chloropyridazine derivative 8 in excellent yield by heating pyridazinone 3b in phosphorus oxychloride. The behaviour of the chloro derivative toward sodium azide, benzyl amine and anthranilic acid was also studied. The proposed structures of the products were confirmed by elemental analysis, spectral data and chemical evidence.