An easy preparation of pyridinium N-heteroarylaminides

Differently substituted pyridinium N-heteroarylaminides have been prepared in one step with good yield from N-aminopyridinium iodide and the corresponding heteroaryl chloride. q 2003 Elsevier Ltd. All rights reserved. For many years conjugated heterocyclic N-ylides, a subgroup of mesomeric betaines, have been widely used as building blocks for the synthesis of fused heterocyclic systems and natural products, due to its 1,3-dipolar character, that allows cycloaddition processes to take place efficiently. Today, cycloimmonium ylides are involved in a wide range of synthetically useful reactions, mainly in the field of heterocyclic chemistry. The chemistry of pyridinium N-(20-heteroaryl)aminides 5 (Scheme 1) has been developed in the last few years taking advantage of its structure, in which a positively charged pyridinium ring coexists with a 2-aminoheteroaryl negatively charged moiety. This peculiar structure would selectively direct the attacking electrophiles, thus allowing easy and selective halogenations on the heteroaryl moiety. – 6 Moreover, N-alkylation process takes place regioselectively over the aminide nitrogen, by the partial blockage of the heteroaryl a-nitrogen, via an intramolecular hydrogen bond. The N–N bond reduction of the resulting pyridinium salts should allow the preparation of the corresponding amines or polyamines. When N-alkylation was performed with a-haloesters or a-haloketones, pyrido[1,2-a]pyrimidin-4-ones and imidazo[1,2-a]pyridines were respectively obtained by a cascade heterocyclisation process. Finally, intramolecular radical arylations of N-haloazinylpyridinium N-aminides afforded dipyridopyrazole and pyridopyrazolepyrazine derivatives. The synthesis of N-aminide intermediates 5 has been traditionally performed by attack of the corresponding 2-heteroaryl hydrazine 2 to 2,4-dinitrophenyl pyridinium chloride 1 (see Scheme 1) generating the hydrazone 3, which is again closed to a pyridinium derivative by acid catalysis, to produce the salt 4 and from there, by treatment with base, the N-aminides were obtained. This method, adapted from the scheme described by Beyer is suitable for available heteroaryl derivatives, usually the simpler pyridylhydrazines. Alternatively, an easy method can be used for various p-deficient heterocycles, by simply treating the N-aminopyridinium iodide 6 with the corresponding 2-chloroheteroaryls 8 in the presence of base. The method generates the pyridinium N-aminides 5 in only one step, and makes a suitable alternative to prepare a diversity of those useful intermediates. The methodology has been applied to the synthesis of N-vinyl, N-imidoyl and fluorinated N-aromatic iminopyridinium ylides. 0040–4020/$ see front matter q 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2003.11.076 Tetrahedron 60 (2004) 1093–1097