A New Synthesis of 8-Methoxypsoralene

Abstract

The present work was undertaken to develop a high-yield synthesis of 8-methoxypsoralene. The proposed synthesis begins with pyrogallol (XIII), which is methylated with dimethyl sulfate to form 1,2,3-trimethoxybenzene (XIV). This is brominated to form 1,5-dibromo-2,3,4-trimethoxybenzene (XV), which is converted to 5-bromo-2,3,4-trimethoxybenzaldehyde (XVI) with butyllithium and dimethylformamide. The methoxy group ortho to the formyl group is then cleaved with boron trichloride, forming 5-bromo-3,4-dimethoxysalicylaldehyde(XVII). Treatment with ethyl bromoacetate and potassium acetate gives ethyl (4 '-bromo-2',3’-dimethoxy-6 ‘-formylphenoxy) acetate (XVIII) which is hydrolyzed with base to give 4'-bromo-2',3'-dimethoxy-6formyl-. phenoxyacetic acid (XIX). Cyclization to 5-bromo-6,7-dimethoxybenzofuran (XX) is done with acetic anhydride, acetic acid, and sodium acetate. Treatment with butyllithium and dimethylformamide gives 6•,7-dimethoxy-5-formylbenzofuran(XXI), and cleavage with boron trichloride gives 5-formyl-6-hydroxy-7-methoxybenzofuran (XXII). The final cyclization to 8-methoxypsoralene (XXIII) is done by the Perkin condensation.