Reaction

The Knoevenagel Condensation Reaction is a classic organic synthesis, described by Emil Knoevenagel in the 1890s. The Knoevenagel reaction is a modified Aldol Condensation with a nucleophilic addition between an aldehyde or ketone, and an active hydrogen compound in the presence of a basic catalyst, resulting in C–C bond formation. The active hydrogen compound contains a C–H bond which can be deprotonated by the basic catalyst. The reaction is usually followed by spontaneous dehydration resulting in an unsaturated product.1

Knoevenagel Condensation Reaction

Figure 1.Knoevenagel Condensation Reaction

Z, Z' (electron withdrawing groups) = CO2R, COR, CHO, CN, NO2, etc.

Knoevenagel’s use of primary and secondary amines, and their salts as catalysts provided an early foundation for the study of aminocatalysts.2 Research continues into synthetic methods using the Knoevenagel condensation with novel new catalysts and reaction activation being reported:

Microwave and ultrasound irradiated reactions3–6
Solvent free conditions7,8
Solid-phase synthesis9
Photochemical condensation with fruit extracts as catalysts10,11

Precautions

Please consult the Safety Data Sheet for information regarding hazards and safe handling practices.

Materials
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References

1.
March J. 1968. in Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, McGraw-Hill. 693697-698.
2.
List B. 2010. Emil Knoevenagel and the Roots of Aminocatalysis. Angew. Chem. Int. Ed.. 49(10):1730-1734. http://dx.doi.org/10.1002/anie.200906900
3.
Vass A, Földesi A, Lóránd T. 2006. Reactions of 3-isochromanone with aromatic aldehydes?microwave assisted condensations performed on solid basic inorganic supports. Journal of Biochemical and Biophysical Methods. 69(1-2):179-187. http://dx.doi.org/10.1016/j.jbbm.2006.03.011
4.
Senguttuvan S, Hemalatha T, Nagarajan S. 2013. Microwave-Assisted Synthesis and Antimicrobial Activities of Some Indenones. Advanced Chemistry Letters. 1(2):187-191. http://dx.doi.org/10.1166/acl.2013.1029
5.
Palmisano G, Tibiletti F, Penoni A, Colombo F, Tollari S, Garella D, Tagliapietra S, Cravotto G. 2011. Ultrasound-enhanced one-pot synthesis of 3-(Het)arylmethyl-4-hydroxycoumarins in water. Ultrasonics Sonochemistry. 18(2):652-660. http://dx.doi.org/10.1016/j.ultsonch.2010.08.009
6.
Lidström P, Tierney J, Wathey B, Westman J. 2001. Microwave assisted organic synthesis?a review. Tetrahedron. 57(45):9225-9283. http://dx.doi.org/10.1016/s0040-4020(01)00906-1
7.
Ware M. 2007. DBU: An Efficient Catalyst for Knoevenagel Condensation under Solvent-free Condition.. Bull. Catal. Soc. India. 6104.
8.
Pasha MA, Manjula K. 2011. Lithium hydroxide: A simple and an efficient catalyst for Knoevenagel condensation under solvent-free Grindstone method. Journal of Saudi Chemical Society. 15(3):283-286. http://dx.doi.org/10.1016/j.jscs.2010.10.010
9.
Guo G, Arvanitis EA, Pottorf RS, Player MR. 2003. Solid-Phase Synthesis of a Tyrphostin Ether Library. J. Comb. Chem.. 5(4):408-413. http://dx.doi.org/10.1021/cc030003i
10.
Pal R. Visible light induced Knoevenagel condensation: A clean and efficient protocol using aqueous fruit extract of tamarindus indica as catalyst. 2(1): http://dx.doi.org/10.14419/ijac.v2i1.1703
11.
Pal R, Sarkar T. 2014. Visible Light Induced Knoevenagel Condensation Catalyzed by Starfruit Juice of <i>Averrhoa carambola</i>. IJOC. 04(02):106-115. http://dx.doi.org/10.4236/ijoc.2014.42012

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