A New Synthesis of 8-Methoxypsoralene
Mayers, Dale J.
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The present work was undertaken to develop a high yield synthesis of 8-methoxypsoralene. The proposed synthesis begins with pyrogallol, which is,methylated with dimethyl sulfate to form 1,2,3-trirnethoxybenzene (XII). This is brominated to form 1,5-dibromo-2,3,4-trlmethoxybenzene (XIII), which is converted to 5-brorno-2, 3,4-trlmethoxybenzaldehyde (XIV) with n-butyllithium and N,N-dimetylformamide at acetone- dry ice, temperatures. The methoxy group ortho to the formyl group is then selectively cleaved with boron trichloride forming 5-bromo-3,4-dimethoxysalicylaldehyde (XV). Overnight reflux with ethyl promoacetate (or methyl bromoacetate) and anhydrous potassium carbonate in reagent grade acetone gives ethyl (or methyl). (4'-bromo-2' ,3'-dlmethoxy-6'-formyl-phenoxyacetate (XVI) which is hydrolyzed to give the .acid (XVII). Cyclization,to 5-bromo-6,7-dlmethoxybenzofuran(XVIII) is done by reflux with acetic acid, acetic, anhydride and sodium acetate. Treatment with n-butyllithium and N,N-dlmethylformamide gives 6,7-dimethyoxy-5-formylbenzofuran (XIX), Cleavage with boron trichloride gives 6-hydroxy7-methoxy-5-formylbenzofuran(XX). The final ring closure to 8-methoxypsoralene is done by reflux with acetic anhydride and sodium acetic.