Structure-reactivity relationships in (2-hydroxyethyl)benzophenone photoremovable protecting Groups

A detailed study of substituent effects on the photochemical conversion of esters of (2-hydroxyethyl)benzophenone to the carboxylic acid was performed with the aim of improving on the reactivity of the parent, which was first reported decades ago. Over 20 derivatives were prepared, 10 of which exhibit some level of photochemical reactivity, but none of them is appreciably better than the original. The reaction did not respond to a thioxanthone as a sensitizer or the inclusion of base to facilitate elimination. Solvent effects on the reaction also seem to be small, with the exception of the perfluorphenyl analog, which is totally unreactive in hexanes but behaves normally in methanol or acetonitrile. These neglected protecting groups may still prove useful in organic synthesis, with fairly rapid deprotection even with long-wavelength irradiation.