An Effective Synthesis of 3-Methoxyflavones via 1-(2-Hydroxyphenyl)-2-methoxy-3-phenyl-1,3-propanediones

Abstract

but yields are very low. 10 Similarly, two oxidation processes of 2'-hydroxychalcones with alkaline hydrogen peroxide 11 or flavones with dimethyldioxirane 12 afford 3-hydroxyflavones, which are then transformed into 3-methoxyflavones with dimethyl sulfate, but the former proceeds with overall low yields, and the latter requires multiple steps. Although some methods for preparing 3-methoxyflavones have been reported, the scope of the problem has not yet been fully investigated. As part of our extending studies of flavones, 13 we describe an effective synthesis of 3-methoxyflavones via 1-(2-hydroxyphenyl)-2-methoxy-3-phenyl-1,3propanediones as key intermediates under relatively mild conditions with high yields. 2'-Hydroxy-2,4'-dimethoxyacetophenone (3) and 2'-hydroxy-2,4',6'-trimethoxyacetophenone (4) were prepared from 3-methoxyphenol (1) and 3,5-dimethoxyphenol (2), respectively, with methoxyacetyl chloride in the presence of aluminum chloride in 1,1,2,2-tetrachloroethane (Scheme 1). The electrophilic aromatic substitution by 2-methoxyacetylium cation occurred exclusively in the 6-position of 1 and the 2-position of 2 and afforded 3 and 4 with 82% and 73% yields, respectively, after acidic workup and chromatographic separation. The 1 H NMR spectra of 3 and 4 showed OH signals at 12.41 and 13.71 ppm, respectively, which are characteristic of ortho-hydroxyl protons. The direct preparation of 1-(2-hydroxy-4,6-dimethoxy