Synthesis and analytical characterization of all N–N-coupled, dimeric oxidation products of α-tocopheramine: hydrazo-, azo-, and azoxy-tocopherol

Abstract

Tocopherols are a mixture of antioxidants which are commonly referred to as vitamin E. Tocopheramines differ from tocopherols by an amino function in lieu of the phenolic OH group. They are potent antioxidants which are used in biomedical scenarios as well as stabilizers for polymers against aging. While in aqueous media α-tocopheramine is mainly oxidized to α-tocopherylquinone and N-oxidized by-products, oxidation in apolar media or in polymeric matrices mainly leads to dimeric compounds of hitherto unknown structure. In the present study, we synthesized the whole array of N,N-dimerization product of α-tocopheramine, including the hydrazo, azo, and azoxy derivatives for the first time, and provided comprehensive analytical data as well as general protocols to access the compounds in straightforward syntheses. These results can now be used to identify the common oxidation by-products of α -tocopheramine in different reaction systems. Graphic abstract

Synthesis and analytical characterization of N-methylated derivatives of α-tocopheramine and their oxidation products

“…To differentiate them only based on their 1 H and 13 C NMR data can thus be rather challenging. 15 N NMR can provide a much better distinction [18,19]: therefore, we used the 15 N-isotopically labeled model compound 1a, in which the isoprenoid side chain is replaced by a methyl group, available from previous work [43], to synthesize the corresponding 15 N-isotopically labeled model compounds (12a-17a). By analogy, many earlier studies on compounds related to vitamin E (α-tocopherol) had relied on the corresponding truncated model compound 2,2,5,7,8-pentamethylchroman-6-ol [44,45].…”

“…α-Tocopherol, by contrast, is produced on a large industrial scale and its oxidation chemistry and reaction products in all kinds of different setups and reaction systems have been extensively described [16,17]. At least the obstacle of unknown degradation products has been removed recently, with the structural elucidation and analytical characterization of all monomeric N-oxidation [18] and dimeric N-N coupling products of α-tocopheramine [19]. It can also be expected that the problem of limited availability will be tackled with new vigor as recent results have shown tocopheramines to be excellent stabilizers for cellulosic fiber spinning from ionic liquid solutions [13] which should result in much greater demand to be met.…”