Synthesis and Trapping of the Elusive Ortho-Iminoquinone Methide Derived from α-Tocopheramine and Comparison to the Case of α-Tocopherol
Abstract
1. Introduction
2. Results and Discussion
3. Conclusions
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- In the α-tocopherol case, the ortho-quinone methide is formed quite readily, with o-QM being a central intermediate in the oxidation chemistry of tocopherol. In contrast, rather special conditions and prerequisites are required for formation of the ortho-iminoquinone methide derived from α-tocopheramine (1). Instead of the formation of ortho-quinoid structures, N-oxidized compounds are the common oxidation products here.
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- In aqueous medium, both α-tocopheramine (1) and α-tocopherol (2) are oxidized neatly to para-tocopherylquinone (7).
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- In the absence of water, 2 forms the corresponding o-QM 3 almost independently of the oxidant and the solvent used, while the formation of o-IQM 5 from 1 was only observed with special oxidants and in solvents of high ionicity, such as ionic liquids or polar aprotic solvents containing dissolved salts.
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- Interestingly, freshly precipitated Ag2O, a particularly mild reagent to generate the o-QM quantitatively from α-tocopherol (2), is also a good reagent to induce o-IQM formation from α-tocopherhydroxylamine (10). While in the former case, it acts as an oxidant that is used in at least equimolar amounts or better in excess, it is a catalyst in the latter case, which cleaves the N-O bond and can be used in substoichiometric amounts (5 mol%). Ag2O does not oxidize α-tocopheramine (1) directly at all.
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- The easy and general formation of 5a-substituted tocopherol via [1,4]-addition to the o-QM intermediate [15,16] has no analog in α-tocopheramine chemistry. The opposite process, the elimination of the 5a-substituent from 5a-substituted α-tocopherols, is a standard reaction in tocopherol chemistry, which always affords the o-QM intermediate. In the tocopheramine realm, the elimination of OH from 5-hydroxy-α-tocopheramine proceeds analogously and affords the o-IQM intermediate. However, it cannot be decided whether this is a general reaction as in the tocopherol case or rather a particular process, because the used 5a-hydroxy-α-tocopheramine is the only 5a-substituted tocopheramine available so far, so no conclusion about the generality of this pathway can be drawn.
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- Trapping the o-QM with ethyl vinyl ether is particularly easy; also, in the o-IQM case, the trapping reagent is very suitable. It is best used, in both cases, as a component of solvent mixtures and thus in large excess.
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- The ratio of trapping with ethyl vinyl ether and dimerization to the spiro-dimer are different for the intermediate ortho-quinoid structures. While the trapping rate is about 10 times faster than dimerization for the o-QM from α-tocopherol (2) [14], the two rates are similar for the o-IQM from α-tocopheramine (1).
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4. Materials and Methods
4.1. Starting Materials
4.2. Formation of o-IQM Intermediate 5, Dimerization, and Trapping Reactions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patel, A.; Rosenau, T. Synthesis and Trapping of the Elusive Ortho-Iminoquinone Methide Derived from α-Tocopheramine and Comparison to the Case of α-Tocopherol. Molecules 2025, 30, 3257. https://doi.org/10.3390/molecules30153257
Patel A, Rosenau T. Synthesis and Trapping of the Elusive Ortho-Iminoquinone Methide Derived from α-Tocopheramine and Comparison to the Case of α-Tocopherol. Molecules. 2025; 30(15):3257. https://doi.org/10.3390/molecules30153257
Chicago/Turabian StylePatel, Anjan, and Thomas Rosenau. 2025. "Synthesis and Trapping of the Elusive Ortho-Iminoquinone Methide Derived from α-Tocopheramine and Comparison to the Case of α-Tocopherol" Molecules 30, no. 15: 3257. https://doi.org/10.3390/molecules30153257
APA StylePatel, A., & Rosenau, T. (2025). Synthesis and Trapping of the Elusive Ortho-Iminoquinone Methide Derived from α-Tocopheramine and Comparison to the Case of α-Tocopherol. Molecules, 30(15), 3257. https://doi.org/10.3390/molecules30153257