Preparation of Highly Reactive Pyridine- and Pyrimidine-Containing Diarylamine Antioxidants.

We recently reported a preliminary account of our efforts to develop novel diarylamine radical-trapping antioxidants (Hanthorn, J. J. et al. J. Am. Chem. Soc 2012,134, 8306-8309) wherein we demonstrated that the incorporation of ring nitrogens into diphenylamines affords compounds which display a compromise between H-atom transfer reactivity to peroxyl radicals and stability to one-electron oxidation. Herein we provide the details of the synthetic efforts associated with that report, which have been substantially expanded to produce a library of substituted heterocyclic diarylammes that we have used to provide further insight into the structure--reactivity relationships of these compounds as antioxidants (see the accompanying paper, DOI: 10.1021/jo301012x). The diarylamines were prepared in short, modular sequences from 2-aminopyridine and 2- aminopyrimidine wherein aminations of intermediate pyri(mi)dyl bromides and then Pd-catalyzed cross-coupling reactions of the amines and precursor bromides were the key steps to yield the diarylammes. The cross-coupling reactions were found to proceed best with Pd(η³-1-PhC3H4)(η5-C5H5) as precatalyst, which gave higher yields than the conventional Pd source, Pd2(dba)3. [ABSTRACT FROM AUTHOR]