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Related Reactions
Acetoacetic Ester Synthesis
Malonic Ester Synthesis

Knoevenagel Condensation
Doebner Modification

The condensation of carbon acid compounds with aldehydes to afford α,β-unsaturated compounds.

The Doebner Modification, which is possible in the presence of carboxylic acid groups, includes a pyridine-induced decarboxylation.


Mechanism of the Knoevenagel Condensation

An enol intermediate is formed initially:

This enol reacts with the aldehyde, and the resulting aldol undergoes subsequent base-induced elimination:

A reasonable variation of the mechanism, in which piperidine acts as organocatalyst, involves the corresponding iminium intermediate as the acceptor:

The Doebner-Modification in refluxing pyridine effects concerted decarboxylation and elimination:

  

Recent Literature


Facile and Highly Stereoselective One-Pot Synthesis of Either (E)- or (Z)-Nitro Alkenes
S. Fioravanti, L. Pellacani, P. A. Tardella, M. C. Vergari, Org. Lett., 2008, 10, 1449-1451.


Phosphane-Catalyzed Knoevenagel Condensation: A Facile Synthesis of α-Cyanoacrylates and α-Cyanoacrylonitriles
J. S. Yadav, B. S. S. Reddy, A. K. Basak, B. Visali, A. V. Narsaiah, K. Nagaiah, Eur. J. Org. Chem., 2004, 546-551.


Reconstructed Hydrotalcite as a Highly Active Heterogeneous Base Catalyst for Carbon-Carbon Bond Formations in the Presence of Water
K. Ebitani, K. Motokura, K. Mori, T. Mizugaki, K. Kaneda, J. Org. Chem., 2006, 71, 5440-5447.


Indium(III)-Catalyzed Knoevenagel Condensation of Aldehydes and Activated Methylenes Using Acetic Anhydride as a Promoter
Y. Ogiwara, K. Takahashi, T. Kitazawa, N. Sakai, J. Org. Chem., 2015, 80, 3101-3110.


The ionic liquid 1-butyl-3-methylimidazonium tetrafluoroborate [bmim]BF4 was used for ethylenediammonium diacetate (EDDA)-catalyzed Knoevenagel condensation between aldehydes or ketones with active methylene compounds. Catalyst and solvent can be recycled.
C. Su, Z.-C. Chen, Q.-G. Zhen, Synthesis, 2003, 555-559.


Ionic Liquid as Catalyst and Reaction Medium - A Simple, Efficient and Green Procedure for Knoevenagel Condensation of Aliphatic and Aromatic Carbonyl Compounds Using a Task-Specific Basic Ionic Liquid
B. C. Ranu, R. Jana, Eur. J. Org. Chem., 2006, 3767-3770.


Organocatalytic Knoevenagel Condensations by Means of Carbamic Acid Ammonium Salts
N. Mase, T. Horibe, Org. Lett., 2013, 15, 1854-1857.


gem-Dibromomethylarenes: A Convenient Substitute for Noncommercial Aldehydes in the Knoevenagel-Doebner Reaction for the Synthesis of α,β-Unsaturated Carboxylic Acids
J. K. Augustine, Y. A. Naik, A. B. Mandal, N. Chowdappa, V. B. Praveen, J. Org. Chem., 2007, 72, 9854-9856.


Organocatalytic Decarboxylative Doebner-Knoevenagel Reactions between Arylaldehydes and Monoethyl Malonate Mediated by a Bifunctional Polymeric Catalyst
J. Lu, P. H. Toy, Synlett, 2011, 1723-1726.


Base-Promoted Cascade Approach for the Preparation of Reduced Knoevenagel Adducts Using Hantzsch Esters as Reducing Agent in Water
T. He, R. Shi, Y. Gong, G. Jiang, M. Liu, S. Qian, Z. Wang, Synlett, 2016, 27, 1864-1869.


A Practical and Convenient Protocol for the Synthesis of (E)-α,β-Unsaturated Acids
A. R. Mohite, R. G. Bhat, Org. Lett., 2013, 15, 4564-4567.


Ionic Liquid as Catalyst and Reaction Medium - A Simple, Efficient and Green Procedure for Knoevenagel Condensation of Aliphatic and Aromatic Carbonyl Compounds Using a Task-Specific Basic Ionic Liquid
B. C. Ranu, R. Jana, Eur. J. Org. Chem., 2006, 3767-3770.