Science of Synthesis

Vanden Eynde, J. J.; Mayence, A., Science of Synthesis: Multicomponent Reactions, (2014) 1, 70.

The most detailed study on the mechanism of the Hantzsch 1,4-dihydropyridine synthesis identified the first two intermediates as being a chalcone ‌10‌ (obtained from an aldehyde ‌8‌ and a β-oxo ester ‌9‌) and an enamino ester ‌11‌ (obtained from ammonia and a β-oxo ester ‌9‌), on the basis of 13C and 15N NMR spectra (‌Scheme 4‌).[‌21‌] Further steps should involve a Michael addition to form the transient species ‌12‌, a ring closure to yield a 2-hydroxy-1,2,3,4-tetrahydropyridine ‌13‌, and finally a dehydration to give the 1,4-dihydropyridine product ‌14‌. Interestingly, analogues of intermediate ‌13‌ have been isolated in some particular cases.[‌22‌–‌24‌]

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References