Selective para-hydroxylation of phenol and aniline by singlet molecular oxygen

Phenol reacts with singlet oxygen (1O2) generated in aqueous solution (H2O or D2O) by (a) the exposure of methylene blue to light or (b) the thermal dissociation of the endoperoxide of 3,3'-(1,4-naphthylidene)dipropionate to lead selectively to hydroquinone as the primary product. The other isomers of phenol hydroxylation, catechol and resorcinol, were not observed. In agreement with the involvement of 1O2 as the reactive species in the hydroxylation, in D2O the yield of hydroquinone is 7 times that in H2O, and the 1O2 quenchers azide and the thiols, glutathione and dithiothreitol, suppress the production of hydroquinone. In contrast, the hydroxyl radical scavengers, tert-butyl alcohol, propanol, or sodium formate, are without effect. In a follow-up reaction, hydroquinone is converted into benzoquinone. Reaction of 1O2 with aniline leads to the selective formation of 4-hydroxyaniline as the initial product. This is further converted to hydroquinone with formation of ammonia (deamination), and then to benzoquinone. On the basis of these results, the selective para hydroxylation of phenol or aniline may be used as an indicator for the involvement of singlet oxygen as compared to .OH radical- or cytochrome P450-mediated reactions.