4,5-Dihydro-6-(4-methoxy-3-methylphenyl)-3(2H)-pyridazinone계 화합물의 합성 연구

Abstract

4,5-Dihydro-6-(4-methoxy-3-methylphenyl)-3(2H)-pyridazinone derivative계 화합물의 합성연구를 수행하였다. 첫 번째로, 4,5-dihydro-6-(4-methoxy-3-methylphenyl)-3(2H)-pyridazinone (1)은 o-cresyl methyl ether와 succinic anhydride를 Friedel-Crafts 아실화 반응을 통하여 얻은 다음에, 고리화 반응을 통하여 합성하였다. 얻어진 화합물 1을, NaOEt조건 하에서, 방향족 알데히드와 반응시켜서 4-substituted benzyl pyridazinones (3a-d)을 합성하였으며, 화합물 1을 탈수소화반응을 시켜서 화합물 4를 얻었다. 한편 pyridazine 5는 화합물 1과 1,3-diphenyl-2-propen-1-one을 Michael 첨가반응을 이용하여 합성하였다. N-Dialkylaminomethyl 화합물 6a-b는 pyridazinone 1과 formaldehyde 및 2차 amine을 바능시켜서 얻은 반면에, 화합물 7은 pyridazinone 1을 반응시켜서 얻었으며, 화합물 8은 pyridazinone 3b를 phosphorus oxychloride 와 반응시켜서 얻었다. 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.