Hantzsch Dihydropyridine (Pyridine) Synthesis
This reaction allows the preparation of dihydropyridine derivatives by condensation of an aldehyde with two equivalents of a β-ketoester in the presence of ammonia. Subsequent oxidation (or dehydrogenation) gives pyridine-3,5-dicarboxylates, which may also be decarboxylated to yield the corresponding pyridines.
Mechanism of the Hantzsch Dihydropyridine Synthesis
The reaction can be visualized as proceeding through a Knoevenagel Condensation product as a key intermediate:
A second key intermediate is an ester enamine, which is produced by condensation of the second equivalent of the β-ketoester with ammonia:
Further condensation between these two fragments gives the dihydropyridine derivative:
'In situ'; Generated 'HCl'; - An Efficient Catalyst for Solvent-Free Hantzsch Reaction at Room Temperature: Synthesis of New Dihydropyridine Glycoconjugates
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Multicomponent Domino Cyclization-Oxidative Aromatization on a Bifunctional Pd/C/K-10 Catalyst: An Environmentally Benign Approach toward the Synthesis of Pyridines
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Covalently Anchored Sulfonic Acid on Silica Gel as an Efficient and Reusable Heterogeneous Catalyst for the One-Pot Synthesis of Hantzsch 1,4-Dihydropyridines under Solvent-Free Conditions
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Facile Yb(OTf)3 promoted one-pot synthesis of polyhydroquinoline derivatives through Hantzsch reaction
L.-M. Wang, J. Sheng, L. Zhang, J.-W. Han, Z.-Y. Fan, H. Tian, C.-T. Qian, Tetrahedron, 2005, 61, 1539-1543.