Protocatechuic acid (= 3,4-dihydroxybenzoic acid; 1) exhibits a significantly slow DPPH (= 2,2diphenyl-1-picrylhydrazyl) radical-scavenging reaction compared to its esters in alcoholic solvents. The present study is aimed at the elucidation of the difference between the radical-scavenging mechanisms of protocatechuic acid and its esters in alcohol. Both protocatechuic acid (1) and its methyl ester 2 rapidly scavenged 2 equiv. of radical and were converted to the corresponding o-quinone structures 1a and 2a, respectively (Scheme). Then, a regeneration of catechol (= benzene-1,2-diol) structures occurred via a nucleophilic addition of a MeOH molecule to the o-quinones to yield alcohol adducts 1f and 2c, respectively, which can scavenge additional 2 equiv. of radical. However, the reaction of protocatechuic acid (1) beyond the formation of the o-quinone was much slower than that of its methyl ester 2. The results suggest that the slower radical-scavenging reaction of 1 compared to its esters is due to a dissociation of the electron-withdrawing carboxylic acid function to the electron-donating carboxylate ion, which decreases the electrophilicity of the o-quinone, leading to a lower susceptibility towards a nucleophilic attack by an alcohol molecule.
Introduction. -Polyphenols are known to exhibit potent antioxidant activities. Recently, numerous studies have been reported on radical-scavenging activities of phenolic compounds. Particularly, structureÀactivityÀrelationship studies of polyphenols and kinetic studies on reactions of phenolic compounds with radicals, including substituent effects, have been extensively investigated [1 -3]. It is well-known that the radical-scavenging activity of phenol-derived acids largely depends on the number and arrangement of phenolic OH groups in the molecule [4 -6]. Among them, o-or p-benzenediol derivatives exhibit high radical-scavenging activity compared to m-benzenediol derivatives, since they could be converted to the corresponding stable o-or p-quinone derivatives [7].
Protocatechuic acid (= 3,4-dihydroxybenzoic acid; 1) and its esters are o-benzenediols, ubiquitously found in edible plants, vegetables, and fruits, and are known to exhibit potent antioxidant activities [4] [8]. Additionally, it has been demonstrated that protocatechuic acid has preventive effects on carcinogenesis and cardiovascular diseases that are associated with free radicals [9] [10].
Previously, we have found that the radical-scavenging reactions of protocatechuic acid (1) and its esters depend on the applied solvents [11]. In non-alcoholic solvents, 1 and its esters scavenge 2 equiv. of radical to yield the corresponding o-quinones. In alcoholic solvents, protocatechuic acid esters rapidly react with more than 4 equiv. of