함질소 헤테로고리 화합물 생성반응에 관한 연구

Abstract

3-Aminocrotonate ester를 200℃로 가열하면 self-condensation product가 얻어진다. 본 연구에서는 이 self-condensation product가 2.6-dimethyl-4-pyrimidone임을 밝혀내고 이러한 생성물이 얻어지는 반응 경로를 추적하기 위하여 3-Aminocrotonamide와 Methyl acetoacetate를 1:1로 혼합하여 반응시켰고, 또한 3-Aminocrotonamide 만으로 가열하여 self-condensation반응을 유발시켰다. 연구의 결과에 의하면 3-Aminocrotonate ester 만으로 condensation 시키면 반응이 느리고 수율이 낮은데 비하여 3-Aminocrotonamide로 self-condensation시키면 반응수율이 높고 반응 속도가 매우 빨라 180℃로 15분 정도면 85%의 수율로 2.6-dimethyl-4-pyrimidone이 얻어진다. 따라서 본 연구에서는 acetoacetate ester가 ammonia 또는 amine과의 반응에서 함질소 헤테로고리 화합물을 형성 할 때는 3-Aminocrotonamide형으로 된 후에 self-condensation을 일으킨다는 결론을 얻었고 이때의 반응 mechanism으로는 Michael-type의 addition-elimination 메카니즘이 작용하는 것으로 추단하였다. Methylacetoacetate와 Ammonial 수용액을 가압 반응시켰을 때에는 4.6-dimethyl-2-pyridone이 주생성물로 얻어졌다. 또한 3-Aminocrotonatemethyl ester의 HCI염을 가열하여 self-condensation 시켰을 때에는 문헌보고와는 달리 4.6-dimethyl-2-pyridone이 높은 수율로 얻어졌다. 본 연구에서는 TLC로 반응을 추적하고 생성물을 용매에 의해 재결정하거나 silica column을 이용하여 분리 정제하고 NMR, IR, 원소분석, M.P. 측정으로 확인하고 Aldrich NMR 또는 IR Catalog와 비교하여 확인하였다.;On heating methyl 3-aminocrotonate to 200℃, it gave self-condensation product, and identified as 2.6-dimethyl-4-pyrimidone. In this study we attempted to search the self-condensation route. The 1:1 mixture of methyl 3-aminocrotonate and methyl acetoacetate was heates to 200℃ and neat solution of 3-arninocrotonarnide to 180℃. Both reactions gave the same compound of 2.6-dimethyl-4-pyrimidone as a main. Self-condensation reaction of methyl 3-arninocrotonate was slow and the chemical yield was low, but the rate of self-condensation of 3-aminocrotonarnide was fast and the product yield was very high. On heating the mixture of methyl acetoacetate and aqueous ammonia and ammonium carbonate, it gave 4.6-dimethyl-2-pyridone, and heating the hydrochloride salt of methyl 3-aminocrotonate also gave 4.6-dimethyl-2-pyridone. From these result we concluded that 2.6-dimethyl-4-pyrimidone forming self-condensation reaction of 3-aminocrotonate ester occurs from the type of 3-aminocrotonamide in the course of reaction, and in the case that 3-aminocrotonamide could not be formed, self-condensation reaction of 3-aminocrotonate ester gives 4.6-dimethyl-2-pyridone, and that nitrogen containing. heterocyclic compounds formed from acetoacetate ester and ammonia can be 2-pyridone or 4-pyrimidone by the reaction conditions. As reaction mechanism, double Michael-type addition elimination reaction was proposed as to formation of 2.6-dimethyl-4-pyrimidone from 3-aminocrotonamide and enamine carbon-carbon bond formation reaction mechanism was proposed to 4.6-dimethyl-2-pyridone from 3-aminocrotonate these can be affected by reaction conditions; temperature, presence of acid or base catalyst or solvent properties. All products were isolated, purified by recrystalization or silica column chromatography and identified by NMR, IR, Elemental analysis, and campared with authentic or literature.