The Reactivity of Air-Stable Pyridine- and Pyrimidine-Containing Diarylamine Antioxidants

We recently reported a preliminary account of our efforts to develop novel diarylamine radical-trapping antioxidants (Hanthorn et al. J. Am. Chem. Soc. 2012, 134, 8306–8309), wherein we demonstrated that the incorporation of ring nitrogens into diphenylamines affords compounds that display a compromise between H-atom transfer reactivity to peroxyl radicals and stability to one-electron oxidation. Herein, we report the results of thermochemical and kinetic experiments on an expanded set of diarylamines (see the accompanying paper, DOI: 10.1021/jo301013c), which provide a more complete picture of the structure–reactivity relationships of these compounds as antioxidants. Nitrogen incoporation into a series of alkyl-, alkoxyl-, and dialkylamino-substituted diphenylamines raises their oxidation potentials systematically with the number of nitrogen atoms, resulting in overall increases of 0.3–0.5 V on going from the diphenylamines to the dipyrimidylamines. At the same time, the effect of nitrogen incorporation on their reactivity toward peroxyl radicals was comparatively small (a decrease of only 6-fold at most), which is also reflected in their N–H bond dissociation enthalpies. Rate constants for reactions of dialkylamino-substituted diarylamines with peroxyl radicals were found to be >10⁷ M^–1 s^–1, which correspond to the pre-exponential factors that we obtained for a representative trio of compounds (log A ∼ 7), indicating that the activation energies (E_a) are negligible for these reactions. Comparison of our thermokinetic data for reactions of the diarylamines with peroxyl radicals with literature data for reactions of phenols with peroxyl radicals clearly reveals that diarylamines have higher inherent reactivities, which can be explained by a proton-coupled electron-transfer mechanism for these reactions, which is supported by theoretical calculations. A similar comparison of the reactivities of diarylamines and phenols with alkyl radicals, which must take place by a H-atom transfer mechanism, clearly reveals the importance of the polar effect in the reactions of the more acidic phenols, which makes phenols comparatively more reactive.