Book of abstracts version 5

Book of abstracts SPOC 2018
3,4-unsubstituted Coumarin analogues
Author
Knoevenagel synthesis of novel
marin analogues
Sjoerd van der Gun
Academy of Technology for Health and Environment
Avans Hogeschool, Breda
Jack van Schijndel
Kees Kruithof
Abstract
Coumarins are widely used as agrochemicals, additives in cosmetics, anticoagulants, antifungal agents or hypnotic and
cytotoxic agents[1] . Common routes to the synthesis of coumarins are the Wittig or Perkin reactions who require strong
acids or bases with high temperatures for long times. These reactions requires toxic solvents while also producing
hazardous waste. Other published synthetic routes to these 3,4 -unsubstituted coumarins from
2-hydroxybenzaldehyde have been equally hazardous, toxic and/or wasteful[2 ] . Therefor a green way of synthesizing
3,4-unsubstituted coumarins will be highly valuable. Recently a new synthetic route for turning benzaldehydes into their
corresponding, -unsaturated acids was reported by van Schijndel et al. (2 017). This technique was reported to be a
solvent-free condensation which uses environmentally benign amines or ammonium salts as catalysts instead of pyridine
and piperidine as used in the traditional Knoevenagel condensation [3]. This research is aimed at gaining more
mechanistic insight into this reaction, by synthesizing coumarin analogues by means of a Green Knoevenagel synthesis in
order to gain more insight into the reaction mechanism as proposed by van Schijndel et al. (2017). This was done by
reacting 2-hydroxybenzaldehyde with diethylmalonate with ammonium bicarbonate as catalyst at two different
temperatures and following the reaction in time by use of HPLC-UV. In this investigation, previously unreported coumarin
analogues have been synthesised and analysed using 400 MHz 1 H-NMR and 13 C-NMR. Showing that the novel green
Knoevenagel synthesis can open the doors to a wide array of previously unknown compounds. Some of which might find
good use in pharmacological or agrochemical industries.
Keywords: Green Chemistry, Knoevenagel, Novel 3,4-unsubstituted Coumarins.
Table of content
Figure 6: Reaction equation.
[1] K. N. Venugopala, V. Rashmi, and B. Odhav, “Review on natural coumarin lead c ompounds for their pharmacological
activity,” BioMed research international, vol. 2013, 2013.
[2] F. G. Medina, J. G. Marrero, M. Maçıas-Alonso, M. C. González, I. Cordova-Guerrero, A. G. T. García, and S. Osegueda-
Robles, “Coumarin heterocyclic derivatives: chemical synthesis and biological activity,” Natural product reports, vol. 32,
no. 10, pp. 1472–1507, 2015.
[3] J. van Schijndel, L. A. Canalle, D. Molendijk, and J. Meuldijk, “Temperature dependent green synthesis of 3 -
carboxycoumarins and 3,4-unsubstituted coumarins,” Letters in Organic Chemistry (To be published), 2017
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