Reactions of furocoumarins. II. Synthetic aminomethyl psoralens via chloromethylation or benzylic bromination

AbstractSeveral psoralen derivatives have been synthesized in order to evaluate their efficacy as photochemotherapeutic (PUVA) agents, including a variety of 4′‐substituted‐4,5′,8‐trimethypsoralen compounds (1d‐j). Improved synthesis of the very potent photosensitizers 8‐methylpsoralen (6a) and 4,8‐dimethylpsoralen (6b) are described and 6a has been shown to undergo formylation in the 4′‐position. Free radical bromination of 6a and 6b with NBS affords primarily 8‐bromomethyl derivatives (8a and d), which are readily converted into the 8‐aminomethyl derivatives (8c and f) by the Gabriel method. If the 4′‐position is blocked, electrophilic substitution apparently occurs primarily in the 5′‐position of the psoralen system. At least, chloromethylation of 4′‐methylpsoralen (9) affords mainly 5′‐chloromethyl derivatives (10a and d), which also lead to aminomethylpsoralens (10c and f).