335199-67-2Relevant articles and documents
Extraordinary kinetic behavior of the α-tocopheroxyl (vitamin E) radical
Bowry,Ingold
, p. 5456 - 5467 (1995)
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.
The "Tocopherol-Acetaminophen Reaction". A New [1,4]-Rearrangement Discovered in Vitamin E Chemistry
Rosenau, Thomas,Kosma, Paul
, p. 947 - 956 (2007/10/03)
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.
