2,4-Dihydroxyacetophenone의 효율적인 Alkylation에 관한 연구

Abstract

Benzophenone과 acetophenone 유도체들은 효과적인 자외선 흡수제로 많이 이용되어지고 있다. 본 연구는 그 중 2,4-dihydroxyacetophenone의 효율적인 alkylation에 관한 것으로 2-hydroxy-4-methoxyacetophenone과 2-hydroxy-4-ethoxyacetophenone을 합성하였다. 이때 alkylating reagent로는 methyl iodide, ethyl iodide, dimethyl sulfate, diethyl sulfate를 사용하였는데, 용매로 아세톤, CH_(3)CN 그리고 THF를 사용하였을 때는 sulfate가 iodide보다 좋은 이탈기 효과를 보였으나 DMF 용매 하에서는 뚜렷한 효과가 나타나지 않았다. 지금까지 입체 장애를 받는 hydroxy기의 acylation 반응의 좋은 촉매로 알려져 온 4-(N,N-dimethyl)aminopyridine(DMAP)을 촉매로 사용하여 그 효과를 관찰한 결과, 극성이 작은 아세톤과 THF 용매에서는 DMAP의 촉매 효과가 나타났으나, 극성이 큰 용매인 DMF와 CH_(3)CN에서는 그 효과를 관찰할 수 없었다. 또한 여러 논문을 통해 주장되어온 DMAP의 촉매 반응 메카니즘을 살펴보고, 본 반응의 메카니즘을 제안하였다. 본 반응에서는 K_(3)PO_(4)가 가장 좋은 염기 효과를 보여주었으며 K_(2)CO_(3), Na_(2)CO(3)와 Li_(2)CO_(3)를 사용하였을 때는 potassium, sodium, lithium 양이온과 2,4-dihydroxyacetophenone 음이온의 ion pair complex 형성으로 그 효과가 K_(2)CO_(3) > Na_(2)CO_(3) > Li_(2)CO_(3) 순서로 관찰되었다. 2,4-dihydroxyacetophenone의 alkylation은 반응 온도가 25℃에서 60℃로 높아질수록 반응 시간이 단축되었으나, DMF 용매에서는 90℃에서 부생성물인 2,4-dimethoxyacetophenone이 생성되기 때문에 2-hydroxy-4-methoxyacetophenone의 수득율은 감소된 결과를 얻었다.;Many studies have been performed for the efficient syntheses of benzophenone and acetophenone derivatives which have been used as UV-Vis light absorbers. In the present study, 2-hydroxy-4-methoxyacetophenone and 2-hydroxy-4-ethoxyacetophenone were prepared by alkylation of 2,4-dihydroxyacetophenone with methyl iodide, dimethyl sulfate, ethyl iodide, and diethyl sulfate. Alkyl iodide was a more reactive alkylating reagent than dialkyl sulfate in acetone, CH_(3)CN, and THF. Iodide and sulfate exerted a similar effect of leaving group in DMF. In this experiment, bases used were K_(3)PO_(4), K_(2)CO_(3), Na_(2)CO)_(3), and Li_(2)CO_(3). It was observed that K_(3)PO_(4) was the most effective base. Also, because of ion pair complex formation with anion of 2,4-dihyroxy- acetophenone, the reactivity order K_(2)CO_(3) > Na_(2)CO_(3) > Li_(2)CO_(3) was observed. 4-( N , N-dimethyl)aminopyridine(DMAP) was found to catalyze the reaction of 2,4-dihydroxyacetophenone with methyl iodide in acetone and THF, but not in CH_(3)CN and DMF. It is suggested that DMAP catalyzed mechanism involved nucleophilic catalysis with the intermediate formation of N-methyl-4-dimethylaminopyridinium iodide for the reaction of 2,4-dihydroxy- acetophenone with methyl iodide. The etherification of 2,4-dihydroxyacetophenone was accelerated in an increased temperature. But the yield of 2-hydroxy-4-methoxyacetophenone decreased because of the formation of 2,4-dimethoxyacetophenone at 90℃