Hantzsch -pyridine synthesis Mechanism

The Hantzsch pyridine synthesis affords 1,4-dihydropyridines 214, although spontaneous oxidation to pyridines often occurs. In its simplest form it involves the condensation of two molecules of a -keto ester with an aldehyde and ammonia (Scheme 119) . Compounds resulting from the condensation of ammonia with one of the carbonyl components can be used in the Hantzsch synthesis. Thus, -aminocrotonic ester 215 can replace the ammonia and one mole of acetoacetic ester in Scheme 119. The mechanism of the Hantzsch synthesis has been clarified by 13C and 1SN NMR spectroscopy <1987T5171>. 

Katritzky, A. R., Ostercamp, D. L., Yousaf, T. I. Mechanism of heterocyclic ring closures. 3. Mechanism of the Hantzsch pyridine synthesis a study by nitrogen-15 and carbon-13 NMR spectroscopy. Tetrahedron 1986, 42, 5729-5738. 

The Hantzsch synthesis of pyridines features 1,4-dihydropyridines in the first step. A variant of the method uses hydroxylamine (Table 17-5), which can be regarded as an oxidized version of ammonia. With this reagent, pyridines are formed directly from 1,5-dicarbonyl compounds, in turn readily made by Michael additions of enolates to a,j8-unsaturated aldehydes and ketones (Section 18-11). Formulate the mechanisms of the two steps in the pyridine synthesis shown. 

Hantzsch (dihydro)-pyridine synthesis Description Historical perspective Mechanism Variations... 

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