During the synthetic studies toward 5,6,7,3′,4′-monomethoxytetrahydroxyflavones, a concise pedalitin synthesis procedure was achieved. As previously reported, 6-hydroxy-2,3,4-trimethoxyacetophenone was prepared by Friedel–Crafts acylation of 1,4-dihydroxy-2,6-dimethoxybenzene with boron trifluoride diethyl etherate in acetic acid. When aldol condensation of 6-hydroxy-2,3,4-trimethoxyacetophenone
2b with vanillin was performed in
[...] Read more.
During the synthetic studies toward 5,6,7,3′,4′-monomethoxytetrahydroxyflavones, a concise pedalitin synthesis procedure was achieved. As previously reported, 6-hydroxy-2,3,4-trimethoxyacetophenone was prepared by Friedel–Crafts acylation of 1,4-dihydroxy-2,6-dimethoxybenzene with boron trifluoride diethyl etherate in acetic acid. When aldol condensation of 6-hydroxy-2,3,4-trimethoxyacetophenone
2b with vanillin was performed in basic conditions, it produced 2′-hydroxychalcone
3b, and, surprisingly, along with 3-hydroxyflavone
4 in a considerable amount. We propose that this oxidative cyclization is presumably due to the contribution of a quinone methide, likely to be subjected to aerobic oxidation. The chalcone was then subjected to oxidative cyclization with iodine in dimethyl sulfoxide to afford flavone
5 in good yield. To our delight, serial demethylation of the three methoxy groups at the 5-, 6-, and 3′-positions of
5 proceeded smoothly to produce pedalitin
1, under hydrogen bromide solution (30% in acetic acid). The crystal structures of 3-hydroxyflavone
4 and pedalitin tetraacetate
6 were unambiguously determined by X-ray crystallography.
Full article
