Knoevenagel Condensation Reaction

Reaction

The Knoevenagel Condensation Reaction is a classic organic synthesis, described by Emil Knoevenagel in the 1890’s. 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

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

     

 References

  1. March, J., in Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, McGraw-Hill, (New York, NY: 1968) pp. 693, 697-698.
  2. List, B., Emil Knoevenagel and the Roots of Aminocatalysis. Angewandte Chemie International Edition, 49(10), 1730-34 (2010).
  3. Vass, A. et al., 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 (2006).
  4. Bhuiyan, M.M.H. et al., Microwave assisted Knoevenagel condensation: Synthesis and antimicrobial activities of some arylidene-malononitriles. Chemistry Journal, 2(1): 30-36 (2012).
  5. Palmisano, G. et al., Ultrasound-enhanced one-pot synthesis of 3-(Het)arylmethyl-4-hydroxycoumarins in water. Ultrasonics Sonochemistry, 18(2) 652-660 (2011).
  6. Lidström, P. et al., Microwave assisted organic synthesis – a review. Tetrahedron, 57, 9225 (2001).
  7. Ware, M. et al., DBU: An Efficient Catalyst for Knoevenagel Condensation under Solvent-free Condition. Bull. Catal. Soc. India, 6, 104 (2007).
  8. Pasha, M.A., and Manjula, K., 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 (2011).
  9. Guo, G. et al., Solid-Phase Synthesis of a Tyrphostin Ether Library. J. Comb. Chem., 5, 408 (2003).
  10. Pal, R., Visible light induced Knoevenagel condensation: A clean and efficient protocol using aqueous fruit extract of Tamarindus indica as catalyst. International Journal of Advanced Chemistry, 2(1), 27-33 (2014).
  11. Pal, R., and Sarkar, T., Visible Light Induced Knoevenagel Condensation Catalyzed by Starfruit Juice of Averrhoa carambola, International Journal of Organic Chemistry, 4, 106-115, (2014).

 

04/15-1

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