DETERMINATION OF THE SEQUENTIAL ORDER OF ACIDITY IN A POLYHYDROXYLATED BENZOPHENONE SERIES - CONSEQUENCE ON THE OXIDATION REACTION IN RELATION TO HEPATOTOXICITY

The pK(a) values of successive acid-base equilibria involved in the py rogallol ring ionization of exifone, 2,3,4-trihydroxybenzophenone 1, a nd related methoxy derivatives were determined by UV-VIS absorption sp ectrometry and potentiometric titration. Due to strong intramolecular hydrogen bonding, the sequential order of acidity of the three hydroxy groups of 1 was found to be 4-OH > 3-OH > 2-OH. The polyhydroxylated benzophenones were oxidized to 3,4-quinone only in a narrow range of a cidity in which the monoanionic 4-olate species predominated in soluti on. The attachment of an amino-alcohol residue resulted in the trappin g of the transient 3,4-quinone and provided a convenient route to nove l 1,4-benzoxazine derivatives. Cytotoxicity experiments in rat hepatoc ytes indicated that some of these compounds were significantly less to xic than the parent exifone.