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<strong>Book</strong> <strong>of</strong> <strong>abstracts</strong> SPOC 2018 3,4-unsubstituted Coumarin analogues Author Knoevenagel synthesis <strong>of</strong> novel marin analogues Sjoerd van der Gun Academy <strong>of</strong> Technology for Health and Environment Avans Hogeschool, Breda Jack van Schijndel Kees Kruith<strong>of</strong> Abstract Coumarins are widely used as agrochemicals, additives in cosmetics, anticoagulants, antifungal agents or hypnotic and cytotoxic agents[1] . Common routes to the synthesis <strong>of</strong> 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 <strong>of</strong> 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 <strong>of</strong> 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 <strong>of</strong> 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 <strong>of</strong> 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 <strong>of</strong> previously unknown compounds. Some <strong>of</strong> which might find good use in pharmacological or agrochemical industries. Keywords: Green Chemistry, Knoevenagel, Novel 3,4-unsubstituted Coumarins. Table <strong>of</strong> 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 <strong>of</strong> 3 - carboxycoumarins and 3,4-unsubstituted coumarins,” Letters in Organic Chemistry (To be published), 2017 23