Knoevenagel缩合反应

反应

Knoevenagel缩合反应是一项经典的有机合成,由Emil Knoevenagel在1890年代首次报道。作为对于Aldol缩合的一种修改,Knoevenagel反应是在碱性催化剂存在下,在醛或酮与活性氢化合物之间发生亲核加成的改性羟醛缩合反应,导致C-C键形成。 活性氢化合物含有可以被碱性催化剂去质子化的C-H键。 通常在反应后自发脱水,产生不饱和产物。

吸电子基团

Z, Z' (吸电子基团) = CO2R, COR, CHO, CN, NO2

Knoevenagel使用伯胺和仲胺以及它们的盐作为催化剂为氨基催化剂的研究提供了早期基础。目前研究的进展以达到使用具有新的催化剂和报道具有新的反应活性的Knoevenagel缩合作为合成的方法:

  • 微波和超声辐射反应3–6
  • 无溶剂条件7,8
  • 固相合成9
  • 以产物作为催化剂的光化学缩合反应10,11
 

注意事项

请查询化学品安全技术说明书(SDS)获取关于危险品和安全操作处置的信息。

 

参考文献

  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).