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

• Published in: Journal of organic chemistry 2012-08, Vol.77 (16), p.6908-6916
• Main Authors: Hanthorn, Jason J, Valgimigli, Luca, Pratt, Derek A
• Format: Article
• Language: English
• Subjects: Catalysis; Catalysts: preparations and properties; Chemical reactivity; Chemistry; Exact sciences and technology; General and physical chemistry; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Organic chemistry; Preparations and properties; Reactivity and mechanisms; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo301013c

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 diarylamines 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 diarylamines. 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.