2-Pyridone ring enamines

The triazole ring can be synthesized by reaction between a suitable pyridine (or piperideine) and an azide. Thus 5-nitro-2-pyridone (or N-substituted pyridones) and sodium azide give a 5-oxotriazolo[4,5-b]pyridine (94)182-184 whereas the enamine 95 reacts with p-nitrophenyl azide to give the hexahydro-l//-triazolo[4,5-c]pyridine 96.185,186... 

Quinolone antibiotics such as ofloxacin 200 are totally different from P-lactams, tetracyclines and so on and work in a different way. They offer some hope that resistance may be slow to appear. They all contain the quinolone core a benzene ring fused to a y-pyridone. Most have various amine substituents and ofloxacin has a fluorine atom. Disconnection of the enamine reveals a benzene ring with a series of heteroatom substituents (N, N, O, F) and the one fluorine suggests that a series of nucleophilic substitutions might provide a synthesis. 

The nucleophilic reactivity of 17 can be increased by N-deprotonation and the best results were obtained with the in situ generated lithium salts. The latter react with acrylates by Michael addition and ring closure to give a single product. The problem of regioselectivity arises because the enamine anion 47 is delocalized and can react both at the nitrogen anion and/or at the enamine carbon. Both cases are known in the literature with similar substrates (ref. 49). These two pathways should lead to the isomeric dihydro a- or y-pyridones (Scheme 53). 

The more common triazine to pyridine ring transformation is illustrated by the formation of pyridines by reaction of 2,5,6-triethoxycarbonyl-1,2, -triazine with both alkynes and enamines.30,31 The addition of vinyl isocyanate to 1-diethylamino-propyne gives mainly the pyridone (1 ) as a result of initial (2+2) cycloaddition followed by rearrangement the thiopyridone (15) is however formed from the corresponding reaction with vinyl isothiocyanate as a consequence of a (A+2)cycloaddition reaction.32... 

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