Pyridinium N-2 0 -pyridylaminide: synthesis of 3-aryl-2-aminopyridines through an intramolecular radical process Ara ´nzazu Sa ´nchez, Araceli Nu ´n ˜ez, Julio Alvarez-Builla and Carolina Burgos * Departamento de Quı ´mica Orga ´nica, Universidad de Alcala ´, 28871 Alcala ´ de Henares, Madrid, Spain Received 19 August 2004; revised 24 September 2004; accepted 28 September 2004 Available online 18 October 2004 Abstract—Tris(trimethylsilyl)silane (TTMSS) and azobisisobutironitrile (AIBN) promote the intramolecular heteroarylation of arenesulfonamides with pyridyl radicals under thermal conditions. The arenesulfonamides are easily prepared from pyridinium N-2 0 - pyridylaminide. The heteroarylation process involves pyridyl radical cyclization and ipso substitution. q 2004 Elsevier Ltd. All rights reserved. 1. Introduction Azinium N-ylides, a subgroup of mesomeric betaines, are interesting compounds due to their dipolar character, as well as to their biological properties and synthetic applications. 1,2 During the past few years our research group has been interested in the chemistry of pyridinium N-2 0 -pyridylami- nide, 1a (Scheme 1), a stable heterocyclic betaine, that has a p-deficient pyridinium fragment attached to a p-excessive 2-iminopyridine moiety. This compound has proven to be a versatile scaffold in a wide range of transformations. Thus, for example, the preparation of 3-or 3,5-halogenated 2-alkyl aminopyridines from 1a can be carried out by an easy and selective halogenation at the iminopyridine moiety (for supply, for example 1b, Scheme 1), followed by regio- selective N-alkylation at the aminide nitrogen and final reduction of N–N bond. 3 During the course of our studies on the intramolecular arylation of 1b, we evaluated the behavior of the pyridyl radical 2 (Scheme 1). The ultimate goal was the preparation of bipyridine 3 by a reaction pathway involving a exo/endo- trig cyclization, followed by N–N bond breaking, as previously described. 3d Compound 3, however, was not detected and instead, the tricyclic derivative 4 was obtained in moderate yield. 4 Following the same target in the development of a preparation of bipyridines and related biaryls by intramolecular radical arylation (i.e., 5, Scheme 1), we decided to prepare salt 6 in order to explore the feasibility of an intramolecular free radical ipso-substitution of the corresponding arenesulfonamides by pyridyl radicals, according to the methodology described by Motherwell and col. 5 This well-established method, based on aryl radical cyclizations, has been applied to the synthesis of biaryls and arylheterocycles. However, to the best of our knowledge, references concerning the use of heteroaryl radicals in such a method have not been published to date. Indeed, from a general point of view, the cyclization of pyridyl radicals has scarcely been exploited in synthesis. 6 0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2004.09.099 Tetrahedron 60 (2004) 11843–11850 Scheme 1. Keywords: Arylation; Biaryls; Ipso-substitution mechanism; Radicals and radical reaction; Tris(trimethylsilyl)silane. * Corresponding author. Tel.: C34 91 885 4618; fax: C34 91 885 4686; e-mail: carolina.burgos@uah.es