N-Iodosuccinimide → Psoralen

Participants

Reaction Steps

Similarly the fluorine atom was introduced during the formation of the pyrone moiety through a Pechmann reaction with ethyl 2-fluoro-acetoacetate as the fluorine carrier. Thus, 3-fluoro-4,8-dimethyl-6-allyl-7-hydroxycoumarin (3, R═F, R′=H) was prepared in 3 steps from 2-methylresorcinol (36% overall yield). Then, ring closure was achieved in two steps in a 66% overall yield following the same route employed with the 3-cyano derivatives giving a mixture 89:11 of (5, R═F, T═Br) and its pyrano isomer (6, R═F) in favor of the expected psoralen. Finally, this 89:11 mixture was reacted with refluxing anhydrous pyridine affording pure target compound (5, R═F, T═pyridinium, Br salt) in 73% yield. Alternatively, the 3-fluoro-6-allyl-7-hydroxycoumarin (3, R═F, R′=H) could be ring closed with NIS in 91% yield to give 3-fluoro-4,8-dimethyl-4′,5′-dihydro-5′-iodomethylpsoralen (5, R═F, T═I). The resulting 3-fluoro-4,8-dimethyl-4′,5′-dihydro-5′-iodomethylpsoralen was reacted with pyridine to form the pyridinium iodine salt (5, R═F, T═pyridinium iodide). Ring closure of 3-fluoro-6-allyl-7-hydroxycoumarin (3, R═F, R′=H) with mercury acetate in ethanol gave the 5′-acetomercurimethyl-4,8-dimethyl-4′,5′-dihydropsoralen (5, R═F, T═HgOAc) in 92% yield.

Provenance & Evidence