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
G. V. M. Sharma, K. L. Reddy, P. S. Lakshmi, P. R. Krishna, Synthesis, 2006, 55-58.
Multicomponent Domino Cyclization-Oxidative Aromatization on a Bifunctional Pd/C/K-10 Catalyst: An Environmentally Benign Approach toward the Synthesis of Pyridines
O. De Paolis, J. Baffoe, S. M. Landge, B. Török, Synthesis, 2008, 3423-3428.
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
R. Gupta, R. Gupta, S. Paul, A. Loupy, Synthesis, 2007, 2835-2838.
Yb(OTf)3 catalyzed an efficient, operationally simple and environmentally benign Hantzsch reaction via a four-component coupling reaction of aldehydes, dimedone, ethyl acetoacetate and ammonium acetate at ambient temperature to yield polyhydroquinoline derivatives in excellent yield.
L.-M. Wang, J. Sheng, L. Zhang, J.-W. Han, Z.-Y. Fan, H. Tian, C.-T. Qian, Tetrahedron, 2005, 61, 1539-1543.