PYRIDINE SYNTHESIS

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.

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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:

Recent Literature

Efficient Synthesis of Hantzsch Esters and Polyhydroquinoline Derivatives in Aqueous Micelles

'In situ'; Generated 'HCl'; - An Efficient Catalyst for Solvent-Free Hantzsch Reaction at Room Temperature: Synthesis of New Dihydropyridine Glycoconjugates

One-Pot Synthesis of 1,4-Dihydropyridines via a Phenylboronic Acid Catalyzed Hantzsch Three-Component Reaction

Multicomponent Domino Cyclization-Oxidative Aromatization on a Bifunctional Pd/C/K-10 Catalyst: An Environmentally Benign Approach toward the Synthesis of Pyridines

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

Aluminum Chloride Promoted Hantzsch Reaction of N-Tosylhydrazones

Facile Yb(OTf)₃ promoted one-pot synthesis of polyhydroquinoline derivatives through Hantzsch reaction