Studies of the Selective O-Alkylation and Dealkylation of Flavonoids. XVIII. A Convenient Method for Synthesizing 3,5,6,7-Tetrahydroxyflavones

Abstract In the demethylation of 6-hydroxy-3,4′,7-trimethoxy-5-(tosyloxy)flavone with anhydrous aluminum bromide, the 5-tosyloxyl group was eliminated with bromination to give 8-bromo-3,6,7-trihydroxy-4′-methoxyflavone as the main product. When anhydrous aluminum chloride was used in the demethylation of the acetate, the 5-tosyloxyl group was cleaved prior to the demethylation to give 5,6,7-trihydroxy-3,4′-dimethoxyflavone. Demethylation of 6-hydroxy-4′,5,7-trimethoxy-3-(tosyloxy)flavone and its acetate with the bromide or chloride afforded the 5,6,7-trihydroxyflavone without the cleavage of the 3-tosyloxyl group, but was not suitable for the general synthesis of the 3,5,6,7-tetrahydroxyflavones because of the difficulty in removing the protecting group. Consequently, it was found that the direct demethylation of 3,6-dihydroxy-5,7-dimethoxyflavones with anhydrous aluminum chloride–sodium iodide in acetonitrile was the most useful general method for synthesizing 3,5,6,7-tetrahydroxyflavones. Additionally, the reported structures of two natural flavones were revised.