Knoevenagel Condensation Reaction

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

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 reactions^3–6
Solvent free conditions^7,8
Solid-phase synthesis⁹
Photochemical condensation with fruit extracts as catalysts^10,11

Precautions

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

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. https://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. https://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. https://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. https://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. https://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. https://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. https://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): https://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. https://doi.org/10.4236/ijoc.2014.42012