Hantzsch Dihydropyridine (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.

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
A. Kumar, R. A. Maurya, Synlett2008, 883-885.

'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, Synthesis2006, 55-58.

One-Pot Synthesis Of 1,4-Dihydropyridines Via A Phenylboronic Acid Catalyzed Hantzsch Three-Component Reaction
A. Debache, R. Boulcina, A. Belfaitah, S. Rhouati, B. Carboni, Synlett2008, 509-512.

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, Synthesis2008, 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, Synthesis2007, 2835-2838.

Aluminum Chloride Promoted Hantzsch Reaction Of N-Tosylhydrazones
H. Wang, M. Tang, Synthesis201749, 4893-4898.

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, Tetrahedron200561, 1539-1543.