Synthesis of 5,6,7-trimethoxyflavone as a key intermediate for the preparation of baicalein

Approaches towards the preparation of 5,6,7-trimethoxyflavone (8), a key intermediate for the synthesis of baicalein, are discussed. Of the synthetic routes, the most efficient was accomplished by direct Fries acylation of trimethoxyphenol (1) with cinnamoyl chloride followed by oxidative cyclization of the resulting chalcone 6 with I 2 /DMSO in good overall yields (70%). Demethylation of 8 using 47% HBr/AcOH readily produced baicalein. The chalcone 6 could also be prepared by Claisen-Schmidt condensation of acetophenone 2 with benzaldehyde catalyzed in alkali.