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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.


A bifunctional polystyrene bearing both DMAP and piperidine groups is an effective organocatalyst for decarboxylative Doebner-Knoevenagel reactions of arylaldehydes and monoethyl malonate to give E-cinnamates in high yields. A synergistic effect obtained by co-locating the two different catalytic amine groups on the same polymer backbone has been detected.
J. Lu, P. H. Toy, Synlett, 2011, 1723-1726.


The use of FeCl3 as catalyst enables a rapid decarboxylation of methylene tethered cyclic 1,3-diesters in the presence of water to yield α,β-unsaturated acids with high E-stereoselectivity under both microwave and conventional heating conditions. This powerful approach proved to be scalable to gram scale synthesis.
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.