3- Aminopyridines 3-pyridyl pyridinium salt

Fluoropyridine. This isomer can be prepared in 54—81% yield by dia2oti2ation of 4-aminopyridine in anhydrous hydrogen fluoride (370,371,400). Eree 4-fluoropyridine readily undergoes self-quaterni2ation to give pyridyl pyridinium salts (401) stabili2ation can be effected as the hydrochloride salt (371,400). Numerous 4-fluoropyridinium salts, eg, 4-fluoro-l-methylpyridinium iodide, have been converted to novel penicillins (387,402). 

This reaction (a) has considerable preparative interest in the case of l-(4-pyridyl)pyridinium salts since it permits introduction of an amino group at position 4 of pyridine. For example, 4-aminopyridine is formed when l-(4-pyridyl)pyridinium chloride hydrochloride is heated with aqueous ammonia for 8 hours at 150°1136 or when ammonia is led into a solution of this salt in phenol for 3 hours at 180-190° (80% yield).1137 Analogously, passing dimethyl-amine into a phenol melt of the salt gives 4-(dimethylamino)pyridine.1138 Under these conditions the quaternary pyridine ring is easily cleaved by aromatic amines, so that 4-(arylamino)pyridines are better synthesized from the pyridylpyridinium salts by means of the hydrochloride of aromatic amines.1139... 

Aminopyridines from ethylenepyridinium salts via (3-pyridyl)pyridinium salts... 

Improved procedures for the Chichibabin amination of pyridine derivatives have been reported (83JAP(K)58-208266, 83USP4386209, 83USP4405790). A general method has been developed for the conversion of 2-aminopyri-dines into 2-pyridones via 2-cthoxycarbonyl-l-(2-pyridyl)pyridinium ions 15. The pyridinium ions 15 are easily made from the 2-aminopyridines 14 and the corresponding pyrylium salt 13. On treatment with aqueous sodium hydroxide, pyridinium ions 15 are converted into the l-(substituted-2-pyridyl-carbonyl)-2-pyridones 16, which are readily hydrolyzed to the 2-pyridones 17 and the picolinic acid 18 (83JCS(P1)2623). 

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