PSORALEN SYNTHESIS - IMPROVEMENTS IN FURANO RING FORMATION - APPLICATION TO THE SYNTHESIS OF 4,5',8-TRIMETHYLPSORALEN

Two methods have been studied in depth for the linear fusion of a furano ring to a coumarin, as applied to the synthesis of 4, 5ʹ,8-trimethylpsoralen. Thus alkylation of 7-hydroxy-4, 8-dimethylcoumarin (9) with 2, 3-dichloro-lpropene followed by Claisen rearrangement and treatment of the rearrangement product with 70% sulfuric acid produces 4, 5ʹ,8-trimethylpsoralen (1) in 70% overall yield from 9. At higher acid concentrations, a dimer of 1 is a major product. Alternatively, amination of hydroxycoumarin 9 by exchange with O-(2, 4-dinitrophenyl)hydroxylamine proceeds in high yield to give the O-coumarylhydroxylamine 13. The oxime 8, formed by condensation of 13 with acetone, rearranges on treatment with acid to give trimethylpsoralen 1 along with 9, the acetonyl ether of 9, and a C-8 acetonyl derivative of 9. © 1979, American Chemical Society. All rights reserved.