Synthesis and Antioxidant Activity of 4H-1,3-Benzodioxin-6-ol Derivatives: New Vitamin E Analogs

Abstract

Abstract 4H-1,3-Benzodioxin-6-ol (HBD) derivatives 1—5, new tocopherol (Vitamin E) analogs, have been synthesized by condensation of acetaldehyde with the corresponding hydroquinone. For each HBD derivative except for 4, two diastereomeric isomers were produced. These stereoisomers were separated by column chromatography and the configuration of each isomer was identified by two dimensional NMR techniques and ESR measurements of the HBD radicals. The second-order rate constants, ks, for the reaction of 9 kinds of HBD derivatives with substituted phenoxyl radical (PhO·) in ethanol have been measured with a stopped-flow spectrophotometer. These HBD derivatives reacted at rates that were only about 5—20% of those observed with the corresponding tocopherols. The logs of the second-order rate constants, ks, obtained for HBD derivatives were found to correlate with their peak oxidation potentials, Ep. Electron spin resonance measurements were done for HBD radicals in toluene, and the proton hyperfine coupling constants, aiH, and giso-values were determined. The log of the rate constants, ks, was also found to correlate with the sum of the hyperfine coupling constants (a5H + a7H) at 5- and 7-positions of both HBD radicals and tocopheryloxyl radicals, that is, the unpaired π-spin densities (ρ5 + ρ7) at the two ortho carbon atoms.