The role of oxygen in the biological activity of the psoralens (furocoumarins) is incompletely understood. Adducts between singlet oxygen (('1)(DELTA)(,g), ('1)O(,2)) and various psoralen derivatives have been postulated as intermediates in the binding of psoralens to protein. Accordingly, a series of psoralens and structurally related benzofurans was prepared and the reaction of these compounds with ('1)O(,2) was studied.

Benzofurans, on photooxidation, were found to undergo 2,3-bond scission yielding keto-ester products. Electron withdrawing or bulky groups on the furan double bond render the compounds inert to photooxidation. Placing an aryl group in the 2-position has the general effect of stopping or, at least, slowing the reaction with ('1)O(,2). Whereas 3-pheylbenzofuran is oxidized rapidly, 2-phenylbenzofuran is unreactive. Models, molecular mechanics calculations and UV data suggest an explanation in terms of a greater amount of resonance interaction between the furan double bond and aryl group in the 2-substituted cases.

The course of benzofuran photooxidations is altered when the reactions are run in the presence of diphenyl sulfide. The type of product obtained depends upon the nature of the benzofuran starting material. Diphenyl sulfide serves to deoxygenate dioxetane intermediates, forming either transient benzofuran epoxides or zwitterionic structures which rearrange or add solvent, giving the observed products. The same products can be obtained by treating the benzofurans with peracids.

Psoralens which contain alkyl or aryl groups on the furan double bond react readily to give dioxetane cleavage-type products. Diphenyl sulfide intercepted photooxidation of these compounds provides evidence for dioxetane intermediates. The products of these reactions are related to proposed intermediates in the metabolism of the psoralens.

Psoralens which lack furan substituents but possess powerful electron donating groups in the 5- and 8-positions give rise to peroxidic intermediates (detected by low temperature NMR) which are stable only at low temperature. The peroxides ultimately give polymeric products.