335199-67-2

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• 335199-69-4 N-{4-[3,4-dihydro-6-hydroxy-2,7,8-trimethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-5-ylmethoxy]phenyl}acetamide 
• 23531-69-3 α-tocopheroxyl radical 

Relevant academic research and scientific papers

Extraordinary kinetic behavior of the α-tocopheroxyl (vitamin E) radical

Rate constants which have been reported for the bimolecular self-reaction of α-tocopheroxyl radicals vary by about 5 orders of magnitude. We have found that the observed bimolecular rate constant can vary by about a factor of 7 during a single, but typical experiment, e.g., in chlorobenzene at 37°C from ca. 7 x 103 M-1 s-1 initially to ca. 1 x 103 M-1 s-1 finally. The overall reaction involves a disproportionation with the transfer of a hydrogen atom from the 5-methyl group of one radical to the phenoxyl oxygen atom of the other radical forming α-tocopherol and an o-quinone methide. In the slow regime (which corresponds to the true reaction of two α-tocopheroxyl radicals) this disproportionation has a deuterium kinetic isotope effect of 3.7. The bizarre kinetic behavior observed with α-tocopheroxyl radicals has been traced to a very minor impurity which will be present in any normal sample of α-tocopherol. The impurity in question is a bisphenol in which two α-tocopherol moieties have become linked through their 5-methyl carbon atoms. This bisphenol is a 'natural' impurity in α-tocopherol since it will be formed upon exposure of α-tocopherol to air. The coupling of two o-quinone methide molecules yields a spiro-dimer which is then reduced to the bisphenol, probably by unoxidized α-tocopherol.

Formation and decay dynamics of vitamin e radical in the antioxidant reaction of vitamin E

In order to understand the dynamics of antioxidant actions of vitamin E (α-, β-, γ-, and δ-tocopherols, TocH) in biological systems, kinetic study of the formation and decay reactions of vitamin E radicals (α-, β-, γ-, and γ- tocopheroxyls, Toc ?) has been performed in organic solvents, using stopped-flow spectrophotometry. By mixing α-, β-, γ-, and δ-TocH with aryloxyl radical (ArO ?) in ethanol, the peaks of the UV-vis absorption due to α-, β-, γ-, and δ-Toe? radical appeared rapidly at ca. 430-340 nm, showed maxima, and then decayed gradually. The second-order rate constants (κa and 2κd) for the formation and decay (that is, bimolecular disproportionation) reactions of a-Toe were determined by comparing the observed curves with the simulation ones obtained by the numerical calculation of differential equations related to the above reactions. From the results, the wavelengths of absorption maxima (λmax i) and molar extinction coefficients (ε) (i = 1-4) of the optical spectra were determined for α-Toc? radical. Notable solvent effects have been observed for the reaction rates (κf and 2κd) and absorption spectra (λmax i and εi) of α-Toc? radical. The scheme of the formation and decay reactions of α-, β-, γ-, and δ-Toc? radicals has been discussed based on the results obtained.

The "Tocopherol-Acetaminophen Reaction". A New [1,4]-Rearrangement Discovered in Vitamin E Chemistry

Treatment of N-{4-[3,4-dihydro-6-hydroxy-2,7,8-trimethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-5-ylmethoxy]phenyl}acetamide (8a) - the Toc prodrug of acetaminophen (7) - with aqueous base yields 4-hydroxy-3-(6-O-α-tocopheryl)acetanilide (10a) as the main product. This hitherto unknown reaction type can formally be regarded either as a rearrangement involving [1,4]-sigmatropic and [1,3]-sigmatropic shifts, or as an intermolecular redox process. Alternative pathways, such as an intermolecular reaction or a free radical process, have been ruled out. The formation of 10a by a multi-step sequence consisting of elimination, redox reaction, 1,4-addition to a quinone intermediate, and rearomatization has also been ruled out, by trapping reactions. During the reaction, a proton from the acetaminophen structure is selectively transferred to C-5a in the tocopheryl moiety as proven by deuteration experiments. The 4'-N-acyl structure is crucial for the reaction to proceed, with the N-acetyl group giving the highest yield of rearrangement product. As 5a-substituted tocopherols are also intermediates in many homolytic reactions of tocopherols in biological model systems, this type of rearrangement might well contribute to the "prooxidative effect" of α-tocopherol, with acetaminophen being replaced by other 5a-substituents that exhibit similar chemical behavior in the reaction.