An Efficient Synthesis of Flavones from 2-Hydroxybenzoic Acids

Abstract

acetoxyphenacyl bromides and benzoyl chlorides also gives flavones, a four step process from 2'-hydroxyacetophenones. In the present paper we report that flavones can be efficiently synthesized in two steps via 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones from 2'-hydroxyacetophenones in high yields. 2'-Hydroxyacetophenones 2, pivotal starting materials for the synthesis of flavones 5, were readily prepared by the treatment of 2-hydroxybenzoic acids 1 with 3 equiv of methyllithium in THF for 2 h between 0 o C and room temperature (Scheme 1). The reaction proceeded smoothly without protection of the 2-hydroxy group to give 2 free from tertiary alcohol after acidic hydrolysis (R 1 =H, R 2 =H; 88%, R 1 =H, R 2 =OMe; 74%, R 1 =OMe, R 2 =H; 90%). The key step in flavones synthesis involves the condensation of the dianion of 2 with benzoylating reagent to give 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones 4. To investigate the optimum reagent for the benzoylation of 2, we added benzoyl chloride, benzoyl cyanide, and 2-pyridyl benzoate to the lithium dianion at 0 o C, which was generated from 2'-hydroxyacetophenone and 2 equiv of lithium diisopropylamide in THF. 1-(2-Hydroxyphenyl)-3-phenylpropane-1,3-dione was obtained in 44%, 55%, and 53% yield, respectively, with the recovery of 2'-hydroxyaceto