Book of Abstracts, SPOC 2017

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Avans University of Applied Sciences 

Lovensdijkstraat 61-63 

4818 AJ Breda 

Postbus 90.116, 4800 RA Breda 

Receptie 088 – 525 75 00 

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Dear reader, 

We present here the Book of Abstracts for the SPOC (Specialisatie Polymeer- en Organische 

Chemie) minor from ATGM (The Academy for Technology of Health and Environment) of Avans 

Hogeschool in Breda. 

In this book of abstract you can find a brief description of the 44 research projects that are 

currently being carried out by the candidates to specialize in Organic and Polymer Chemistry. 

The topics of research span form the green synthesis of monomers for biobased-polymers or 

the application of new polymerization techniques, to the synthesis of biomimetic systems for 

the photodynamic therapy of cancer, bioimaging, peptides for gas phase studies and water 

oxidation catalysis. 

Every year ATGM students enthusiastically work on their specialization projects for 20 weeks 

during which they deepen their knowledge of organic chemistry and the management of a small 

research projects commissioned by different companies and universities, or research institutes 

in the Netherlands and abroad. 

We invite you to come to the poster session on June 28th in LD022 where you will be able to 

meet and discuss with the students responsible for their own research, their results and insights 

on their topics. 

We wish you enjoy the poster presentation and this book of abstracts and we hope to be able 

to welcome you on June 28th . 

Yours sincerely, 

Annabelle, Justin, Koen and Paula 

“The Book of Abstracts Committee” 

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Bart van den Broek 

ATGM Academie voor Technologie Gezondheid en Milieu 

Avans Hogeschool, Breda 

Sonny van Seeters 

According to the biobased lecture, research must be done to biobased monomers for example styrene. In this 

research it will look at different techniques to make block-co-polymers of styrene and another monomer. A wellknown 

technique to make such block-co-polymers is by using a RAFT agent [1]. By using RAFT agent the properties 

of the polymers can affected. Think of de Mn, PDI and Tg of the polymers. The only drawback is that while using a 

RAFT agent for the polymerization it will cost a lot of money to purchase a RAFT agent. 

The goal of this research is to synthesize one or more RAFT agent which also could be used for RAFT 

polymerization. Expected is that a minimum of 1 RAFT agent successfully will be synthesized and purified for a 

RAFT polymerization. 

Keywords: Polymerization • RAFT polymerization • RAFT agent 

[1] Coenraad, W. H. (2013). Frankrijk Patent No. 11306648.4 

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John Schrauwen 



Sonny Van Seeters, Lectoraat Biobased Products 

Commissioned by the lectorate Biobased Products was to gather information and experience with the controlled 

radical polymerization technique Atom Transfer Radical Polymerization. During this project styrene and n-butyl 

acrylate were (co-)polymerized using Cu(I)Br and PMDETA as catalyst and the use of mono and bifunctional 

initiators in ethyl acetate or toluene in a closed and deoxygenated system. Reaction conversion determined 

gravimetrically with attempts to use HPLC and GC and resulting polymers were analysed with GPC and DSC. 

Keywords: SARA ATRP • Cu(0) • Ethyl acetate. 

[1] Peng, C. et al.(2014)”AGET and SARA ATRP of styrene and methyl methacrylate mediated by 

pyridyl-imine based copper complexes”, European Polymer Journal, 51, 1, 12-20. 

[2] Matyjaszewski, K. & Xia, J. (2001)”Atom Transfer Radical Polymerization”, Chemical Reviews, 101, 

9 , 2921- 2990. 

[3] Matyjaszewski, K. (2012)”Atom Transfer Radical Polymerization (ATRP): Current Status and Future 

Perspectives”, Macromolecules, 45, 10, 4015-4039. 

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Sam Compiet 




Now a days most of the monomers used for polymerizations are produced in the petrochemical sector. The 

Research group for Biobased Products, at Avans University of Applied Sciences, is doing research on developing 

monomers that are based on natural products. When the Research group can achieve to produce biobased 

monomers they have to be sure that those monomers can be used to be polymerized. In this research, emulsion 

polymerisation will be investigated in different types: Conventional Emulsion polymerisation, mini-emulsion 

polymerization and, RAFT mini-emulsion. The different techniques are compared to see what is the best technique 

to polymerize the biobased monomers. Before using the biobased monomers, styrene and butyl acrylate are used 

to get an impression how well the different emulsion polymerization techniques work. Five emulsion 

polymerisations and three mini-emulsion polymerizations are executed. Each polymerisation is different from 

each other on one or two variables. These polymerizations are analysed with Differential Scanning Calorimetry 

(DSC) and Size Exclusion Chromatography (SEC). By comparing the GPC results it showed that in both emulsion 

and mini-emulsion the PDI was lower when a controlled transfer agent (CTA) was used. Also in mini-emulsion the 

PDI was lower under RAFT conditions than under normal mini-emulsion conditions. DSC showed that the Tg of 

polystyrene polymers were between 103.38 and 110.03°C. It also showed that a polystyrene-co-butyl acrylaat is 

formed, with a Tg of 39.66°C. Both techniques can be used to polymerize, at this moment only mini-emulsion can 

be used to polymerize under RAFT conditions. 

[1] M. Oliveira, S. L. Behrends, I. R. Rosa, C. L. Petzhold, “Use of a Trithiocarbonyl RAFT Agent without 

Modification as (Co)Stabilizer in Miniemulsion Polymerization”, Journal of Polymer Science, part A: Polymer 

Chemistry, 2017, 00, 000-000 

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Thomas Broers 




Green chemistry is an important subject for the future. In the plastic industry loads of plastic are made out of 

harmful substances. The substances aren’t environmental friendly. A possible solution is the use of biobased 

monomers, these monomers don’t always have the same characteristics. RAFT polymerization is a controlled 

polymerization where different monomers can be coupled in blocks which influences the characteristics by using 

different monomers. This research is the first step in the investigation of using biobased monomers combined 

with RAFT polymerization. The focus will be on the kinetics of the RAFT polymerization and comparison between 

harmful and biobased monomers. 

Keywords: RAFT • styrene • butylacrylate • biobased • kinetics 

A co-polymer is already obtained shown by the lowered Glass transition temperature(Tg). The original styrene 

Tg was 110°C , the Tg 34°C shows the coupling of butylacrylate due the RAFT mechanism. 

[1] W.C. Bear, “RAFT polymerization of poly(butyalacrylate) homopolymer and block coplolymers: kinetics and 

pressure-sensitive adhesive characterization”, ongepubliceerd eindwerk, University of North Carolina 

Wilmington, Wilmington, 2011. 

[2] B. Ebeling en P. Vana, “Multiblock Copolymers of Styrene and Butyl Acrylate via Polytrithiocarbonate- 

Mediated RAFT Polymerization”, Polymers, Vol. 3, pp. 719-739, Maart 2011. 

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Thomas Timmermans 




The Biobased lectoraat is researching monomers derived from natural products. When the monomers are been 

create, they must be able to polymerize. Free radical polymerizations are tested and working with 4- 

acetoxystyrene, but controlled polymerizations as RAFT and ATRP are not widely discussed. This research is done 

to create block-copolymers with RAFT and ATRP, this part of the research is about create the RAFT-agent, because 

RAFT-agents are very expensive molecules. Probably because purify the molecule is a hard part of the synthesis. 

The synthesis of the RAFT-agent is performed with potassium tert-butoxide, n-dodecanethiol, carbon disulfide, 

iodine and heptane and THF as solvent. The product will be analyzed with FTIR, NMR, HPLC and LC-MS. 

Keywords: Polymerization • controlled polymerization • RAFT-agent • FTIR • NMR • HPLC • LC-MS 

Reaction of n-dodecylthiol with carbon disulfied 

Coupling with iodine 

Reaction with AIBN 

[1] Destarac, M. (2011). On the Critical Role of RAFT Agent Design in Reversible Addition-Fragmentation Chain 

Transfer (RAFT) Polymerization. Polymer Reviews, 51(2), 163–187. 

http://doi.org/10.1080/15583724.2011.568130 

[2] Ponnusamy, K., Babu, R. P., & Dhamodharan, R. (2013). Synthesis of block and graft copolymers of styrene 

by raft polymerization, using dodecyl-based trithiocarbonates as initiators and chain transfer agents. Journal 

of Polymer Science Part A: Polymer Chemistry, 51(5), 1066–1078. http://doi.org/10.1002/pola.26466 

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Tim Zoontjens 




Chain growth polymerization is a polymerization technique that makes 80% of the synthetic polymers. Radical 

polymerization is by far the most widely used technique in this area. The result of this technique is a large 

distribution of molecular weights with a large difference in polymer lengths. However, the limits of free-radical 

polymerization are small variations of monomers, which can be used, and block copolymers can’t be polymerized 

with this radical polymerization. 

For this reason, research will be done on a controlled polymerization technique, atom transfer radical 

polymerization. This allows polymers to be synthesized with a low PDI (polydispersity) value and predetermined 

molecular weights and glass rubber transfer temperatures. 

The purpose is to synthesize different block copolymers with the monomers styrene, 4-acetoxystyrene, butyl 

acrylate and methyl acrylate using the catalyst CuBr and the ligand N ', N', N, N '' , N "- 

pentamethyldiethylenetriamine with initiator dimethyl 2,6-dibromoheptanedioate and bromoacetonitrile and 

using toluene as solvent. The aim is to analyze these different polymers with HPLC (conversion), SEC (molecular 

weight) and DSC (glass rubber transition temperature). 

Polymers with low PDI values and conversions below 100%, around 90% are expected. In addition, a linear 

relationship between the conversion and de molar mass is expected. 

Keywords: Block copolymers • Atomic transfer radical polymerization • High-performance liquid chromatography 

• Differential scanning calorimetry • Size exclusion chromatography 

[1] Matyjaszewski, K en Beers K. L. “Controlled/Living Radical Polymerization in the Undergraduate 

Laboratories. 2. Using ATRP in Limited Amounts of Air to Prepare Block and Statistical Copolymers of n-Butyl 

Acrylate and Styrene”, journal of Chemical Education, vol. 78, No. 4, pp. 547-550, 2011. 

[2] Davis, K. A. En Matyjaszewski, K., “Atom transfer radical polymerization of tert-butyl acrylate and 

preparation of block copolymers”, Journal of macromolecules, vol. 33, pp. 4039-4047, 2000. 

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Finn Adema 



Jack van Schijndel & Dennis Molendijk 

One of the principles of Green Chemistry is removing or limiting solvent. Last year [1,2], it was proven that cinnamic 

acid and p-coumaric acid form dimers under the influence of UV-light. The aim of this research was to measure 

the speed of conversion of para-substituted cinnamic acids derivatives under influence of UV-light. The 

investigated cinnamic acids were p-coumaric acid, 4-methoxycinnamic acid and 4-fluorocinnamic acid. It was 

expected that p-coumaric acid form dimers the fastest, followed by 4-methoxy and finally 4-fluorocinnamic acid. 

The research starts with a Knoevenagel condensation of the benzaldehydes that forms the investigated cinnamic 

acids. After the cinnamic acids are synthesized, the cycloaddition is preformed and measured with melting point 

and TLC. If the cinnamic acid derivative forms into a dimer, the conversion will be determined with HPLC, IR and 

NMR. 

Keywords: Solvent free chemistry UV light, cinnamic acids 

[1] M. van Steen ‘’Fotodimerisatie van kaneelzuurderivaten’’, 2016 

[2] B. Snijders ‘’ Dimerisatie van kaneelzuur(derivaten) onder invloed van UV licht’’, 2016 

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Maarten Harijgens 



Avans Biopolymergroup & Technical university Eindhoven (TUE) 

Coumarins are an important group of aromatic compounds which can exhibit a broad biological activity. The 

target molecule 7,8 dihydroxycoumarin , commonly known as daphnetin, excels as an anticoagulant, antioxidant, 

rat-poison, possible antitumoral and as a protein kinase inhibitor. [1][2] The current synthesis is trough expensive 

and environmental unfriendly method, with solvents like piperidine and pyridine. For this reason the Avans 

bioplymergroup and TUE has created a greener alternative to these chemical reactions. The main reaction utilize 

the Knoevenagel condensation to synthesis coumarins from benzaldehydes and malonic acid. To aid them in 

their research, the main goal for this minor project is to synthesise Daphnetin sticking to the general reaction 

route without making drastic changes. The set hypothesis Is to successfully synthesise Daphnetin on mild 

temperatures without disintegrating the desired product. To achieve the set goal, the following method is used: 

2,3,4 trihydroxybenzaldehyde reacts with malonic acid through a Knoenenagel condensation under mild 

conditions, whereas ammonium bicarbonate acts as catalyst for 4 hours on 60 0 C. this synthesis results in 

7,8dihydroxy-3carboxycoumarin which is decarboxylated through an Adams carboxylation. This will result in the 

desired product Daphnetin. [3] In the end, the total cost of synthesis will be around 20 euro per 0,5 – 1 gram, if 

successful. This a fairly cheap in comparison to the selling price of Daphnetin at Sigma Aldrich, which is 336 euro 

for 25 mg. [4] 

Keywords: Knoevenagel condensation • coumarines • daphentin 

[1] Daphnetin, one of coumarin derivatives, is a protein kinase inhibitor. Yang EB, Zhao YN, Zhang K, Mack P. 

Biochem Biophys Res Commun. 1999 Jul 14 

[2] Differential effects of esculetin and daphnetin on in vitro cell proliferation and in vivo estrogenicity. Jiménez- 

Orozco FA 1 , et al, Eur J Pharmacol. 2011 Oct 1 

[3] A Green Chemical Synthesis of 3-Carboxycoumarins and 3,4-unsubstituted Coumarins, Jack van 

Schijndelab*, Luiz Alberto Canallea, Dennis Molendijka, Jan Meuldijkb , to be published. 

[4] link to sigma aldrich: http://www.sigmaaldrich.com/catalog/product/sigma/d5564?lang=en&region=NL 

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Mike Boessen 

ATGM Academy of Technology, Health- and life Sciences 

Avans University of Applied Sciences, Breda 

Avans Biopolymers Group, Eindhoven University of Technology 

Coumarins have a broad range of biological activity in different organisms and are most commonly used in 

medication (anticoagulants), antioxidants, antifungals, rodenticides and even in cosmetics and foods. 

The current general synthesis pathway is a non-environmentally friendly method. In this age green chemistry is 

becoming an ever more important cornerstone of science and this experiment will thus focus itself on altering the 

synthesis route of coumarins to a more green route, which includes a green version of the Knoevenagel 

condensation. 

The main goal of this research is to synthesize ethyl 2-oxochromen-3-carboxylate, coumarin and an intermediate 

in the synthesis of coumarin via a green Knoevenagel condensation from 2-hydroxybenzaldehy and, respectively, 

diethylmalonate or malonic acid using ammonium bicarbonate as promotor. 

Mass Spectrometric analysis has verified the synthesis of both ethyl-3-coumarincarboxylate and its intermediate 

which are both shown the table of content with their mass spectra. 

Keywords: Green chemistry • Knoevenagel condensation • coumarin • ethyl-3-coumarincarboxylate 

[1] A. Shaabani, R. Ghadari, A. Rahmati and R. A. H., “Coumarin Synthesis via Knoevenagel Condensation 

Reaction in 1,1,3,3-N,N,N',N'Tetramethylguanidinium Trifluoroacetate Ionic Liquid,” Journal of the Iranian 

Chemical Society, no. 6, pp. 710-714, 2009. 

[2] A E. Knoevenagel, “Ueber eine Darstellungsweise der Glutarsäure,” European Journal of Unorganic chemisry, 

vol. 2, no. 27, pp. 2345-2346, 1894. 

[3] D. Bogdal, “Coumarins: Fast Synthesis by Knoevenagel,” Journal of Chemical Research, no. 8, pp. 468-469, 

1998. 

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Mike Nuiten 



Jack van Schijndel 

In a study of Jack van Schijndel, The Green Knoevenagel condensation reaction is tested for the synthesis of 

synapinic acid. The action is proven after which this same synthesis is used in this study for the synthesis of 

coumarin derivatives. The goal is to prove that the synthesis route works for as many derivatives as possible. The 

research shows that the synthesis works for R1 to R4 = H and in addition, also R1 = OH, R2 to 4 = H. 

In addition to traditional synthesis with malonic acid, the use of the alternative Meldrum's Acid (cyclic form of 

malonic acid) is tested and proven. 

Keywords: Coumarine derivatives • Green Knoevenagel • Malonic Acid • Salicylaldehyde • Meldrum’s Acid 

HO 

O 

O 

+ 

OH 

R 4 O 

R 4 

R 3 H 

R 3 

NH 4 

HCO 3 

R 2 OH 180 °C 

R 2 

R 1 

R 1 

O O 

[1] L. A. C. J. S. J. M. Jack van Schijndel, „Conversion of Syringaldehyde to Sinapinic Acid through Knoevenagel- 

Doebner Condensation”. Research Group Biopolymers, Centre of Expertise BioBased Economy, Avans 

University of Applied Science, Breda, The Netherlands. Department of Chemical Engineering and Chemistry, 

Lab of Chemical Reactor Engineering/Polymer Reaction Engineering, Eindhoven.. 

[2] V. A. T. S. G. ⇑. F. E. Serena Fiorito, „A green chemical synthesis of coumarin-3-carboxylic and cinnamic acids 

using crop-derived products and waste waters as solvents”. Patent Department of Pharmacy, University ‘G. 

d’Annunzio’ of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo, CH, Italy. 

[3] D. Bogdal, „Coumarins Fast Synthesis by the Knoevenagel Condensation under Microwave 

Irradiation.”. Patent Institute of Organic Chemistry, Politechnika Krakowska ul. Warszawska 24, 

31155 Krakow, Poland; 

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Remon Heemskerk 



Jack van Schijndel, Dennis Molendijk 

One of the principles of “Green Chemistry” is the limitation of solvent or solvent free reaction. In previous 

researches showed that cinnamic acid derivatives can react in an [2+2] cycloaddition under the influence of UV 

light without solvent. In these paper cinnamic acid, ferulic acid, sinapic acid and p-coumaric acid were investigated. 

These compounds were radiated with UV A light with a wavelength varying between 320 and 420 nm. p-Coumaric 

acid and cinnamic acid both reached a 100% conversion to its dimer. This was confirmed with DSC, FTIR and H- 

NMR analysis. [1] [2] This project is focused on the synthesis of different functional groups in cinnamic acid 

derivatives. In this research methylthiocinnamic acid and 4-biphenylcinnamic acid are investigated. p-Courmaric 

acid is also investigated in this research as a reference. [3] 

Keywords: Green chemistry • cinnamic acid • cycloaddition 

[1] B. Snijders, “Dimerisatie van kaneezuur(derivaten) onder invloed van UV licht,” Breda, 2016. 

[2] M. v. Steen, “Fotodimerisatie van kaneelzuurderivaten,” Breda, 2016. 

[3] K. Sugiyama, H. Takayanagi and E. Noguchi, “Substituent effect on the solid-state photochemistry of 

cinnamic acid derivatives,” vol. 2003, no. 36, pp. 40-60, 2003. 

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Daan van de Velde 



Kees Kruithof, Jack van Schijndel 

Green chemistry becomes more popular and important. Therefore a green method is used to perform the 

Knoevenagel condensation reaction. The main goal is to synthesize 2,3,4-trihydroxybenzaldehyde to a styrene 

derivative, via the decarboxylation of its corresponding cinnamic acid derivative. 2,3,4-Trihydroxystyrene has 

three hydroxyl groups, and therefore it was anticipated it could function as good glue when polymerised to a 

polymer. The green Knoevenagel condensation reaction was carried out with 2,3,4-trihydroxybenzaldehyde, 

ammonium bicarbonate and malonic acid. The reaction was carried out without solvent. The expected product 

was a 2,3,4-trihydroxy cinnamic acid, but another reaction occurred between 2,3,4-trihydroxybenzaldehyde and 

malonic acid. The product was very polar and was purified by recrystallization in water. UV/VIS HPLC shows one 

signal, so there are no other uv-visible active components present. Different analyses such as LC-MS, 1H-NMR and 

13C-NMR proved that a coumarin-variant with carboxylic acid group has been synthesized. However, it is 

interesting that the coumarin is formed in a green way. Coumarin is used in the pharmaceutical industry and is 

often made through the Wittig or Perkin reaction. These reactions have a lower E factor, are less green and have 

lower yields. The reason that this reaction occurs is the ortho-hydroxy group. A condensation reaction takes place 

between the dicarboxylic acid and the ortho-hydroxy group. This reaction does not occur when using 3,4- 

dihydroxybenzaldehyde, a hydroxyl benzaldehyde without a hydroxyl group on the ortho-position, in the 

Knoevenagel reaction. This product reacts together with malonic acid to the corresponding cinnamic acid 

derivative, therefore this reactant would be a better alternative to synthesis a styrene-variant with two or more 

hydroxyl groups. To obtain the styrene-variant from the cinnamic acid-variant there only a decarboxylation 

reaction required. 

Keywords: 2,3,4-trihydroxybenzaldehyde • 3,4-dihydroxybenzaldehyde • Coumarin derivate • Green • Glue • 

Monomer • Knoevenagel condensation reaction • Decarboxylation • 1H-NMR • 13C-NMR • LC-MS 

[1] van Schijndel, J., et al., The Green Knoevenagel Condensation: Solvent-free condensation ofbenzaldehydes, 

manuscript. 

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Jim van Hassent 



Lectoraat Biobased Products, Jack van Schijndel en Kees Kruithof 

Polystyrene is currently one of the most widely used plastics. Polystyrene is mainly used for packaging materials, 

insulating materials and household appliances. Polystyrene is not biodegradable and the monomer styrene is 

carcinogenic and toxic. Due to the rising costs of crude oil and concerns about environmental pollution, interest 

in potentially biobased plastics increases significantly. The purpose of this research is to synthesize the biobased 

monomer 4-vinylguaiacol with the green knoevenagel condensation to replace the monomer styrene. [1] 

Following this, 4-vinylguaiacol is acetylated to the monomer 4-acetoxy-3-methoxystyrene. After synthesizing the 

monomer 4-acetoxy-3-methoxystyrene, the monomer is polymerized by free radical polymerization. [2] 

The properties of the resulting polymer are determined using DSC, GPC and FTIR. Poly-4-vinylguaiacol is expected 

to be an amorphous polymer having a Tg of 86 ° C, it is also expected that the polymer has a higher hardness and 

modulus of elasticity than styrene. [3] 

Keywords: Polystyrene • biobased plastics • green knoevenagel condensation • 4-vinylguaiacol 

[1] van Schijndel, J., et al., The Green Knoevenagel Condensation: Solvent-free condensation of benzaldehydes 

[2] T. H. and H. H. Kunio Nakamura, “Nakamura K. Polymer Journal 1986.” 

[3] H. Leisch et al., “Chemicals from agricultural biomass: Chemoenzymatic approach for production of 

vinylphenols and polyvinylphenols from phenolic acids),” 

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Kayleigh van Bale 



Jack van Schijndel, Kees Kruithof 

Self-healing materials are an interesting topic in the Green chemistry, an example of these self-healing materials 

can be created by using a Diels-Alder reaction. This reaction causes to bind two molecules together, which can be 

broken again with applying heat to the material [1]. This binding and breaking reaction causes a self-healing ability 

in the material itself [2]. The purpose of this project is synthesizing and analyzing this coupling and breaking 

mechanism, to test the durability of this reaction. This will be done using HPLC, TLC and FTIR. The reaction will be 

done with N-methylmaleimide and furfurylacetate to create a Diels-Alder product. 

Keywords: Diels-Alder • retro Diels-Alder • HPLC 

[1] V. Froidevaux, et al., study of the diels-alder and retro-diels-alder reaction between furan derivatives and 

maleimide for the creation of new materials, RSC Advances, 2015. 

[2] Jinhui Li, et al., Thermally reversible and self-healing novolac epoxy resins based on Diels–Alder chemistry, 

Journal of Applied Polymer Science, DOI: 10.1002/APP.42167 

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Maartje Otten 



Kees Kruithof, Jack van Schijndel 

Nowadays green chemistry is becoming a more important topic during scientific research. Therefore, a 

green procedure is used to synthesise a styrene analog from syringaldehyde. The main goal is to perform 

a polymerization with a biobased styrene analog made out of syringaldehyde and to investigate the 

physical and mechanical properties. Polystyrene, one of the most used polymers worldwide, is made 

from the toxic monomer styrene and should therefore be replaced for nontoxic and biobased polymers. 

For the production of the styrene analog the green Knoevenagel condensation reaction is performed 

with ammonium bicarbonate and malonic acid combined with a decarboxylation performed by using 

heat and a small amount of ammonium bicarbonate. The reaction is performed with a minimal amount 

of ethyl acetate as solvent. The expected product of these combined reactions is canolol and is analysed 

with FTIR and HPLC with a uv-vis detector. HPLC showed that the product also consisted of canolol diand 

trimers. Because of the present hydroxyl group in canolol the product has been acetylated to 

perform a radical polymerization. The acetylation reaction is performed using acetic anhydride and 

triethylamine. The amount of acetic anhydride and triethylamine used for the reaction was found out 

to be very crucial and should be very precise. After that a solution polymerization and suspension 

polymerization has been performed. The products of the polymerizations are subsequently analysed 

with size exclusion chromatography and differential scanning calorimetry. 

Keywords: syringaldehyde • green Knoevenagel condensation • decarboxylation • acetylation • styrene analog • 

green chemistry • HPLC uv-vis • solution polymerization • suspension polymerization 

[1] van Schijndel, J., et al., The Green Knoevenagel Condensation: Solvent-free condensation of benzaldehydes, 

unpublished results. 

[2] Nakamura, K., et al., DSC Studies on Hydrogen Bonding of Poly(4-hydroxy-3,5-dimethoxystyrene) and 

Related Derivatives, Polymer Journal, vol. 18, p. 219-225, 1986. 

[3] Vicari, R., et al., Process for the suspension polymerisation of 4-acetoxystyrene and hydrolysis to 4- 

hydroxystyrene polymers, US 4962147, 1990. 

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Pricilla Moerland 



Avans Biopolymerengroep, Royal Cosun, TU Eindhoven, Rijksuniversiteit Groningen 

In collaboration with Avans Biopolymer Group, Royal Cosun, TU Eindhoven and Rijksuniversiteit Groningen, an 

research has been launched about biobased styrene analogues, including HMVF (5-hydroxymethyl-2-vinylfuran) 

synthesized from HMF. Poly-HMVF can be used as a versatile glue. It can bind to a variety of substrates, such as 

metal, glass, plastic and rubber, under heating or acid treatment at room temperature [1,2]. HMF is converted to 

its dicarboxylic acid through a green Knoevenagel condensation, after which decarboxylation follows to HMVF. 

This research focuses mainly on the decarboxylation, the purpose of this research is to develop and compare 

decarboxylation methods, where the dicarboxylic acid is decarboxylated to HMVF. The starting product, HMF, has 

been synthesized from D-fructose with Amberlyst-15 as a catalyst. Next, HMF is converted to its dicarboxylic acid 

with malonic acid and ammonium bicarbonate, this concerns the green Knoevenagel condensation [3]. The 

carboxyl groups must be removed by decarboxylation, 4 different methods are carried out and compared. This 

concerns a decarboxylation with Cu2O (combined with HMTA), CuI (combined with 1,10-phenantrioline), KOAc or 

AgOAc [4,5]. Cu2O provides a decarboxylation to its monocarboxylic acid, decarboxylation to HMVF should be 

further investigated. KOAc and CuI decarboxylation results in an unknown product, with the same retention time 

on HPLC-DAD analysis (to be continued). This peak is not found when a decarboxylation with AgOAc is carried out, 

also a lot of by-products are formed using this method. 

Keywords: HMF • Green Knoevenagel condensation • decarboxylation • HMVF 

[1] Miaomiao Han, et al., 5-Hydroxymethyl-2-vinylfuran: A biomass-based solvent-free adhesive, Green 

Chemistry: The Royal Society of Chemistry, 2013. 

[2] Naoki Yoshida et al., Brand-new Biomass-based Vinyl Polymers from 5-Hydroxymethylfurfural (HMF), 

Polymer Journal, V40, No. 12, 2008, P 1164–1169. 

[3] Jack van Schijndel et al., The Green Knoevenagel Condensation: Solvent-free Condensation of Benzaldehydes, 

2016. 

[4] Lukas J. Gooßen et al., Comparative Study of Copper- and Silver-Catalyzed Protodecarboxylations of 

Carboxylic Acids, ChemCatChem V2, 2010, P 430 – 442. 

[5] [5] Kunitsky et al., Method for preparing hydroxystyrenes and acetylated derivatives thereof, US 0228191 A1, 

Oct. 13, 2005. 

28

Rik Mermans 

ATGM Academy of technology, health and environment (academie voor Technologie Gezondheid en Milieu) 

Avans university of applied sciences, Breda 

Kees Kruithof and Jack van Schijndel 

Sinapinic acid be synthesised from aldehydes via the green knoevenagel Doebner reaction. The aldehydes can be 

derived from lignine in wood, the following sinapinic acid can decarboxylate too canolol a biobased styrene variant 

[1]. The decarboxylation of the sinapinic acid is not very efficient and will produce a lot of di- and trimers of canolol. 

Decarboxylation have been described with several similar compounds, which used copper(I) and silver(I) 

complexes for decarboxylation [2-4]. The decarboxylation was carried out with a copper(I)iodide 1,10 

phenanthroline complex in PEG-400 as benign solvent in a microwave, and yielded surprising results. According to 

HPLC analysis the canolol obtain after a simple liquid/liquid extraction was up to 90 to 95% purity with only a small 

residue of sinapinic acid and di- and trimers. 

Keywords: Microwave Decarboxylation • sinapinic acid • canolol • biobased styrene variants 

[1] Jack van Schijndel et al “the green knoevenagel condensation: solvent-free of benzaldehydes” manuscript 

[2] Lucak J. Gooßen et al “Comparative Study of Copper- and Silver-CatalyzedProtodecarboxylations of 

Carboxylic Acids” ChemCatChem, 2012, vol 2, p 430-442 

[3] Yong Zou et al “CuI/1,10-phen/PEG promoted decarboxylation of 2,3-diarylacrylic acids: synthesis of 

stilbenes under neutral and microwave conditions with an in situ generated” recyclable catalyst” 2013, 

Organic en Biomolecular Chemistry, vol 11, p 6967- 6974. 

[4] Stéphane Cadot et al “Preparation of functional styrenes from biosourced carboxylic acids by copper 

catalyzed decarboxylation in PEG” 2014, Green chemistry, vol. 16, p 3089- 309 

29

30

Amber Jaspars 




PET is a thermoplastic polymer which is produced in large numbers for example soda bottles, food packaging and 

textile industry. By the mechanical recycling of PET the chain length will become shorter and the properties of the 

polymer will decrease. By the chemical recycling of PET, PET will be depolymerized and the chemical identity will 

be saved. In this way new molecules and polymers can be build. In this project PBOx6 will be synthesized from old 

PET-bottles. The first step is to make the intermediate BHPTA by an aminolysis. With a cyclization the BHPTA can 

be synthesize to PBOx6 [1]. 

PBOx6 is a coupling agent, across linking agent or a chain extender[1]. For example it will link 2 broken PET polymer 

together, so the chemical identity will be the same as the last bottle. 

Keywords: PET-bottles waste • PBOx6 • BHPTA • recycling 

[1] Rikhil V. Shah, Vasant S. Borude and Sanjeev R. Shukla “Recycling of PET Waste Using 3-Amino-1-propanol by 

Conventional or Microwave Irradiation and Synthesis of Bis-oxazin therefrom”, journal of applied polymer 

science, 2013, DOI 10.1002/app.37900 

31

Jur Brunsting 

ATGM Academie voor Technologie Gezondheid en Milieu, Avans Hogeschool, Breda 

Biobased, Avans Hogeschool 

In modern day society, recycling of waste products becomes more important every day. One of the most abundant 

waste materials is PET, mostly from food and beverage packages. PET can be recycled to form new PET, but this 

will cause the chains to become shorter. To counter this effect, linking molecules can be added. These molecules 

can also be used for linkage of phenoles, diols and dicarboxylic acids. 

The project focuses on the synthesis of PBOx7, seen below as the bottom structure, from BHBuTA, seen below as 

the middle structure, through a ring closure. BHBuTA is synthesized from PET soft drink bottles by aminolysis. 

Keywords: PBOx7 • PBOx6 • PBOx5 • aminolysis • ring closure • linking chemistry 

[1] Al-Sabagh, “Greener routes for recycling of polyehtylene terephthalate” 

[2] S. Shukla, “Aminolysis of polyethylene terphthalate waste” 

[3] R. Shah, “Recycling of PET waste using 3-amino-1-propanol by conventional or microwave irradiation and 

synthesis of bis-oxazin there from” 

32

W.J.M van Oorschot 




Oxazolines are 5-membered heterocyclic rings containing one oxygen and one nitrogen atom, and are well known 

in polymer chemistry [1]. Here they function as monomer [2] in cationic ring-opening polymerisation (CROP), chain 

extender [1, 3] or cross-linker molecules coupling to the aliphatic carboxylic acid chain ends to increase mass 

and/or to give specific properties to the material Besides, 2-oxazolines can be obtained from polyethylene 

terphtalate (PET) recycling process. In this work the reactivity of a model 2-oxazoline (phenyloxazoline) (PhOx) 

towards aromatic carboxylic acids (ACAs) is determined in terms of conversion, to get a better understanding of 

the reaction. The conversion is measured with Reversed Phase High Performance Liquid Chromatography (RP- 

HPLC) and characterized with LC-MS. Coupling reactions are performed at microscale level using benzoic acid (BA), 

terephtalic acid (TPA) and trimeric acid (TA) as ACAs at various temperatures (100-, 150- and 200°C). All three 

ACAs showed coupling with PhOx within two hours with negible side reactions. The following reactivity was found: 

BA > TA > TPA. BA already reached conversion of ~99% after 10 min at 200°C, however TPA and TA reached only 

50-60% after 10 min. Both the mono and bis coupling products for TPA, and the mono, bis and tris-products for 

TA were mainly formed at 100°C, while reactions at 200°C almost immediatly formed the bis or tris-product for 

TPA and TA, in respect. Furthermore, the influence of the lewis acid ZnCl on the conversion was determined at 

100°C for both BA and TPA, resulting in a significantly higher conversion. This study indicates that beside standard 

aliphatic carboxylic acids, the tested ACAs; benzoic acid, terephtalic acid and trimeric acid can undergo a coupling 

reaction with PhOx. 

Keywords: 2-oxazoline • carboxylic acid • coupling reaction • PET recycling • microscale synthesis 

[1] L. Néry, H. Lefebvre en A. Fradet, „Kinetic and Mechanistic Studies of Carboxylic Acid-Bisoxazoline Chain- 

Coupling Reactions,” Macromol. Chem. 2003, 204, 1755-1764 

[2] A. Makino en S. Kobayashi, „Chemistry of 2-Oxazolines: A Crossing of Cationic Ring-Opening Polymerization 

and Enzymatic Ring-Opening Polyaddition,” Journal of Polymer Science, 2010, vol. 48, 1251-1270 

[3] T. Loontjes, K. Pauwels, F. Derks, M. Neilen, C. Sham en M. Serné, „The Action of Chain Extenders in Nylon- 

6, PET, and Model Compounds,” Polymer Science, 1997, vol. 65, 7, 1813-1819 

33

Mike Dirks 



Oxazolines are 5-membered ring structures containing one nitrogen and one oxygen atom. 

2-substituted oxazolines can be obtained as a product in a recycling process of polyethylene terephthalate (PET) 

[1]. These oxazolines can be used as ligand catalysts, protecting groups, as a monomer in cationic ring opening 

polymerization or as a reagent in reactions with a wide variety of compounds [2]. In this study, the reactivity of 2- 

phenyl-2-oxazoline (PhOx) towards phenolic compounds was determined. This was done by carrying out reactions 

between PhOx and various phenolic compounds on a micro synthesis scale, at varying reaction conditions. The 

influence of the reaction temperature and presence of a catalyst was determined by measuring the conversion of 

PhOx using high performance liquid chromatography (HPLC). 

Keywords: Oxazolines • Phenols • Coupling reaction • PET recycling • Micro synthesis 

[1] Rikhil V. Shah, Vasant S. Borude, Sanjeev R. Shukla, „Recycling of PET Waste Using 3-Amino-1-propanol by 

Conventional or Microwave Irradiation and Synthesis of Bis-oxazin There From,” Journal of applied polymer 

science, pp. 1-6, 2012. 

[2] J. A. Frump, „Oxazolines, their preparation, reactions, and applications,” Chemical reviews, pp. 483-505, 

1971. 

34

Thom van der Ende 

ATGM Academy Technology, Health and Environment 


MKB, Avans group Biopolymers 

In our daily life we encounter a lot of plastics which often contain pigment components which are unfriendly for 

the environment. Therefore it is necessary to develop a biobased method for the production of so called 

colormasterbatches (CMB). Expected is that a CMB can be made by a simple aldol-condensation [1] between 4- 

Hydroxybenzaldehyde (4-HB) (1) and acetone or acetylacetone to form a curcumin like molecule (2, 3). Due to the 

aromatic property this component should have a red color. It is found that curcumin blocks the growth factor of a 

cancer cell [2]. But due to the bio-obtainability of curcumin it is important to develop curcumin like derivatives 

which may have the same effect on cancer cells but have a better uptake in the human body. 

In this study various aldolcondensaties between 4-HB and acetone has been carried out using NaOH as a base 

catalyst. Two methods for the reactions were compared, one was using a condenser and one was not using a 

condenser, assuming using no condenser gives better yield. The reactions where followed by TLC and HPLC 

analyses. In all cases a red substance was formed. The reactions using a condenser formed two products, 

presumably mono-4-HBA (2) and Di-4-HBA (3). The reaction without condenser formed only one product which is 

does not match the retention time of the products of the reaction with condenser. Separation of the was 

successfully carried out with column chromatography. But according to HPLC analyses the components before and 

after purification didn’t match. Idendentification by LC-MS analyses hasn’t been obtained yet. 

This study will continue in investigating the reaction between 4-HB and acetylacetone using boride complexes. 

Keywords: 4-Hydroxybenzaldehyde • HMF • color master batch • anticancer • aldolcondensation reaction 

[1] L. Wade, „Organic Chemistry 8th,” Pearson, pp. 1098-1117. 

[2] M. Heger, „Een wonderlijke wortel en een fanatieke onderzoeker versus twee dodelijke ziekten,” 

17 July 2016. [Online]. Available: https://nieuws.nl/populair/20160717/wonderlijke-wortel-en-fanatieke-onderzoeker-versusalvleesklierkanker/. 

35

Justin Kroos 



In this day and age, a world without dyes and colorants is imposible to imagine. These compounds have unlimited 

applications in utilitarian objects and food. The current market of dyes is dominated by compounds which can 

have a negative impact on the environment. The widely applicable building block HMF (5-hydroxymethylfurfural) 

can be synthesized by dehydration of monosacharides and can therefore be considered a biobased building block. 

In this research, we aimed to synthesize several HMF-based dyes by coupling HMF with acetone and acetylacetone 

(yielding bis-HMFA and tris-HMFAA, respectively) in presence of a basic catalyst. This was carried out under 

conventional dehydration conditions and by evaporation driven condensation, after which the results were 

compared. In this respect, the emphasis was placed on the formation of the mono product of HMF and 

acetylacetone (HMFAA). This compound could be the basis of other dyes by coupling it with other aromatic 

compounds instead of HMF. The coupling of HMF with acetone and acetylacetone yielded a solid or oil of which 

its solution was colored brightly yellow and darker yellow, respectively. 

Keywords: Fructose • hydroxymethylfurfural • dye • colorant • biobased 

[1] Gürses, A., & al., e. (2016). Dyes and Pigments. Springer. 

[2] Mehta, A. (2012). Ultraviolet-Visible (UV-Vis) Spectroscopy – Woodward-Fieser Rules to Calculate 

Wavelength of Maximum Absorption (Lambda-max) of Conjugated Carbonyl Compounds. Opgeroepen op 

Maart 8, 2017, van Pharmaxchange.info: http://pharmaxchange.info/press/2012/08/ultraviolet-visible-uvvis-spectroscopy-%E2%80%93-woodward-fieser-rules-to-calculate-wavelength-of-maximum-absorptionlambda-max-of-conjugated-carbonyl-compounds/ 

[3] University of Liverpool. (sd). UV-conjugation of Aniline Yellow and Janus Green . Opgeroepen op Maart 10, 

2017, van Chemtube : http://www.chemtube3d.com/DyeAnilineyellow.htm 

[4] Wade, L. G. (2014). Organic Chemistry. Pearson. 

36

Martijn Knoope 

Avans University of Applied Sciences 

Breda 


Curcumin and its derivatives are strongly coloring substances that can be used in a green color masterbatch. 

Syringaldehyde is seen as a promising derivative on vanillin, that has the same coloring properties. In a reaction 

with acetone or acetylacetone an intense yellow to red color is expected. A continuous supply of syringaldehyde 

is available from lignin, which is a waste product in the pulp industry and a big side-product is in the conversion of 

biomass to bio-ethanol. Syringaldehyde is also available from the cell walls of plants, this makes it the second most 

common biopolymer beyond cellulose and thus a green starting product. In this project two different catalysts for 

the synthesis of mono-syringaldehyde-acetone and mono-syringaldehyde-acetylacetone are examined. In 

addition both catalyst are also compared with a more reactive derivative of syringaldehyde, hydroxymethylfurfural 

(HMF). 

Keywords: Syringaldehyde • color masterbatch • aldolcondensation • knoevenagel condensation • green 

chemistry 

[1] Ibrahim, M. N. Mohamed en R. Sripransanthi, „A concise review of the natural existance, synthesis, 

proerties, and applications of syringaldehyde,” BioResources, pp. 4377-4399, 2012. 

[2] L. Wade, Organic Chemistry, Amerika: Pearson Education, 2015. 

[3] F. Rouessac en A. Rouessac, Chemical analysis, West Sussex: John Wiley & Sons, 2007. 

37

38

Annabelle Dijk 

ATGM Academie van technologie gezondheid en milieu 


Research group analysis techniques in the Life Sciences (ALS) 

Edward Knaven 

Taxanes, including paclitaxel and docetaxel, are known for their anti-cancer activity. Paclitaxel naturally occurs in 

different taxus species. There is one disadvantage and that is that to obtain paclitaxel the taxus plant has to be 

destroyed. As a result, the long term availability is scarce. There are a variety of other taxanes present in the taxus, 

for example 10-deacetylbaccatin III (10-DAB). 10-DAB can be isolated from the leaves of the taxus, therefore the 

plant does not have to be destroyed. 10-DAB can be used for the semi-synthesis of docetaxel and paclitaxel. The 

aim of this project is to synthesize N-tert-Butoxycarbonyl-3-phenylisoserine side chain, and coupling it to 10-DAB. 

The first step in synthesizing the side chain is de esterification of phenylglycine and reducing it with LiALH4 to an 

primary amine alcohol. The next step is the attachment of the tert-butoxy group through an carbonylation of the 

amine with di-tert-butyl-dicarbonate. After that the formation of an aldehyde through an Swern oxidation 

reaction. The aldehyde undergoes an alkylation reaction with vinylmagnesium bromide and after oxidation with 

ruthenium oxide it results in the N-tert-Butoxycarbonyl-3-phenylisoserine side chain. The next step in the synthesis 

of docetaxel is the protection of the hydroxyl groups, present on 10-DAB, with trimethylsilyl chloride. Once they 

are protected, the N-tert-Butoxycarbonyl-3-phenylisoserine side chain can be linked with the 10-DAB with 4- 

Dimethylaminopyridine (DMAP), and after deprotection of de hydroxyl groups , docetaxel is formed. 

[1] Jean-Noel Denis, et al., Direct, Highly Efficient Synthesis from (S)-+( ) -Phenylglycine of the Taxol and 

Taxotere Side Chains, J. Org. Chem. 1991,56,6939-6942. 

[2] Sunay V. Chankeshwara, et al., Catalyst-Free Chemoselective N-tert-Butyloxycarbonylation of Amines in 

Water, organic letters, 2006 Vol. 8, No. 15, 3259-3262. 

[3] Van der Does, Thomas, SALT OF PHENYLGLYCINE METHYL ESTER, DSM Sinochem Pharmaceuticals 

Netherlands B.V., Neth. 

39

Bas van de Velde 



research group analysis techniques in the Life Sciences (ALS) 

Edward Knaven 

Paclitaxel, a diterpenoid (toxoid) with four rings, are a type of chemotherapy medication used to treat varies types 

of cancer, including ovarian, breast and lung cancer [1]. Initially almost all paclitaxel was derived from the bark of 

different Taxus species, the harvesting of which has a destructive effect on the tree [2]. The content of paclitaxel 

in Taxus is low (about 6 – 600 µg/g) [3], and the demand for paclitaxel as cytostatic drug exceeds the supply, which 

has pushed different Taxus species on the brink of extinction. However, some metabolites related to paclitaxel, 

for example 10-DAB, are more abundantly available in Taxus species. In this work, a core-shell molecular imprinted 

polymer (MIP) using emulsion polymerisation was prepared in order to separate 10-DAB from crude Taxus baccata 

L. extract. The core-shell was prepared using methyl methacrylate (MMA) and ethylene glycol dimethylacrylate 

(EGDMA) as monomers. In the imprinting polymer, 10-DAB was used as template molecule; methacrylic acid 

(MAA) and EGDMA were used as functional monomers; and CaCO3 was used as porogenic agent to increase 

porosity. The synthesizes MIP was characterised using Scanning electron microscopy (SEM), Dynamic light 

scattering (DLS), Thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). 

Keywords: Core-shell • Molecular imprinted polymer • toxoids • 10-DAB • emulsion polymerisation 

[1] Wianowska, D.; Hajnos, M. Ł; Dawidowicz, A. L.; Oniszczuk, A.; Waksmundzka-Hajnos, M.; Głowniak, K. 

Extraction Methods of 10-Deacetylbaccatin III, Paclitaxel, and Cephalomannine from Taxus baccata L. Twigs: 

A Comparison. Journal of Liquid Chromatography & Related Technologies 2009, 32, 589. 

[2] Cao, X.; Tian, Y.; Zhang, T. Y.; Ito, Y. Separation and purification of 10-deacetylbaccatin III by high-speed 

counter-current chromatography. Journal of Chromatography A 1998, 813, 397-401. 

[3] Fu, Y.; Zu, Y.; Li, S.; Sun, R.; Efferth, T.; Liu, W.; Jiang, S.; Luo, H.; Wang, Y. Separation of 7-xylosyl-10-deacetyl 

paclitaxel and 10-deacetylbaccatin III from the remainder extracts free of paclitaxel using macroporous resins. 

Journal of Chromatography A 2008, 1177, 77-86. 

40

Egor Silin 



University of Utrecht 

To prevent the adhesion of the bacteria Pseudomonas aeruginosa to human bodycells, researchers of the 

University of Utrecht have developed an inhibitor consisting sugar molecules as building blocks [1]. Those in 

inhibitors are at first divalent, but after using a coupling bridge to combine two of the same molecules, the inhibitor 

becomes tetravalent. The main goal of this study is to synthesis this coupling bridge using 4-dimethoxybenzene 

and tetra ethylene glycol as starting products. The expected yield for this product will be around 70% using 4 

different synthesis steps. First of all, the 4-dimethoxybenzene was transformed in to 1,4-Dimethoxy-2,5- 

diiodobenzene using Iodide and potassium iodate in an acidic solution. After that, the 1,4-Dimethoxy-2,5- 

diiodobenzene was transformed in to 2,5-diiodo-4-methoxyphenol using Lithium Aluminium Hydride under 

nitrogen. Tetraethyleneglycol was used to transform it in to ditosyltetraethylene glycol using toluenesulfonyl 

chloride and a strong base. After the syntheses of those products, both of them were combined to create the final 

product using sodium hydride. 

Keywords: Bacterial Inhibition • Pseudomonas aeruginosa • Nucleophilic Substitution and Elimination 

[1] Pertici F., de Mol N.J., Kemmink J., Pieters R.J., Optimizing Divalent Inhibitors Pseudomonas aeruginosa 

Lectin LecA by Using A Rigid Spacer, Chemistry, A European Journal, 16923-16297 

41

Joyce van der Made 


Avans hogeschool, Breda 

University of Utrecht 

Cancer is one of the biggest problem in the world. A lot of people dying, because of this disease. With the 

technology of this century, there are cures for the different kind of cancer. One of this cures is a body-like 

substance, such as galectins. This are proteins which can be helpful to trace and defeat the cancer. The purpose 

of this project is to make the first steps towards the synthesis of 3-azido derivate of galactose, which is needed for 

the C(3) substituted thiodigalactosides. [1] [2] So the synthesis of 3-O-acetyl-1,2,5,6-di-O-isopropylidene-α-Dgulofuranose 

from 1,2,5,6-diacetone-α-D-glucofuranoside must performed. Also the products can be analysed 

with 1H- and 13C-NMR (Nuclear Magnetic Resonance) and determined the yield. The expectation of this project 

was that the yield of 3-O-acetyl-1,2,5,6-di-O-isopropylidene-α-D-gulofuranose 66% is with a purity of 76%. With 

NMR the different peaks are found which are characterizing for this product. There should be performed three 

syntheses. The first synthesis with pyridinium dichromate (PDC) and acetic anhydride were performed to change 

the hydroxy-group to a ketone. The second reaction with pyridine and acetic anhydride were performed to change 

the ketone to a acetoxy-group. The last reaction was with H2 and palladium on carbon to flip over the acetyl- and 

the diacetone-group. The syntheses was followed with TLC and analyzed with NMR, HPLC and LC-MS. 

Keywords: Cancer • galectins • thiodigalactosides • NMR • TLC 

Figure 1: The whole synthesis of 3-O-acetyl-1,2,5,6-di-O-isopropylidene-α-D-gulofuranose from 1,2,5,6-diacetoneα-D-glucofuranoside 

[1] Zhou, S. ‘’Galectins in channel catfish, Ictalurus punctatus: Characterization and expression profiling in 

mucosal tissues’’ Fish and Shellfish Immunology, 2016, 49, 324-335. 

[2] Cummings, R. D, ‘’Galectins. In A. Varki’’ Essentials of Glycobiology, New York: Cold Spring Harbor, 2009. 

42

Mikey Immers 



Edward Knaven, lectorate ALS 

Taxoids and in particular Paclitaxel are known as mitotic inhibitors which are able to inhibit the growth of tumors 

by inhibiting microtubule polymerization and thus preventing cells from entering mitosis, taxoids are potential 

chemotherapeutic agents against cancer. However currently the problem research is facing is the separation of 

the components of a mixture of taxoids [1]. Hence why a method of molecularly imprinted polymers (MIPs) with 

core shell of nanoparticles is being developed in order to isolate 10-Deacetylbaccatin III as precursor from 

Paclitaxel. With the use of molecular imprinting it is possible to synthetize cross-linked polymers that are capable 

of selective molecular recognition, which is the interaction between molecules through noncovalent bonding [2]. 

The characterization of the MIPs after template removal will be determined with the use of RP-HPLC. Whereas the 

morphology and structure of the MIPs will be researched by a scanning electron microscope (SEM) to image 

polymer macro-pores. And dynamic light scattering (DLS) will be applied to determine the particle size distribution 

and polydispersity index. 

Keywords: Taxoids • Molecular Imprinted Polymers • Mitotic inhibitors • 10-Deacetylbaccatin III • Paclitaxel Core 

shell 

[1] B. Joshi, "An NMR and LC–MS based approach for Mixture Analysis involving Taxoid molecules from Taxus 

wallichiana," Journal of Molecular Structure, pp. 235-248, 25 October 2002. 

[2] M. Gagliardi, "Molecularly Imprinted Biodegradable Nanoparticles," Scientific reports, pp. 1-9, 10 January 

2017. 

43

Nienke Hoetelmans 



Lectoraat Analysetechnieken in Lifescience (ALS) 

Edward Knaven 

A major problem in today's society is the disease cancer. Paclitaxel is an antimitotic cytostatics inhibitor and can 

withstand certain types of cancer. Paclitaxel is naturally present in Taxus baccata . This is at such low 

concentrations that synthesis routes are sought to make this substance in large quantities. Therefore, a synthesis 

has been performed to get paclitaxel in hand. First, the side group of N-benzoyl-β-phenylisoserine was 

synthesized, then coupled to 10-deacetylbaccatin III, which is naturally also present in the Taxus baccata, and is 

highly similar to paclitaxel.[1] The purpose of this study is to synthesize paclitaxel using a starting substance 

resembling paclitaxel, and obtained from the Taxus. [2] In this study 10-deacetylbaccatin III is used. This will be 

coupled to N-benzoyl-β-phenylisoserine, and must be synthesized first properly under the appropriate conditions. 

It is expected that if the reaction is carried out under the appropriate conditions, N-benzoyl-β-phenylisoserine and 

paclitaxel can be synthesized with a low yield. And at least, to identify paclitaxel, it will be analysed with FTIR, HPLC 

and LC-MS. 

Keywords: Paclitaxel • N-benzoyl-β-phenylisoserine • 10-DAB • cancer • Taxus baccata 

Synthesis of N-benzoyl- β-phenylisoserine 

[1] E. Baloglu, „A New Synthesis of Taxol ® from Baccatin III.,” 1998. 

[2] A. C. a. A. E. G. Jean-Noel Denis, „Direct, Highly Efficient Synthesis from Phenylglycine of the Taxol and 

Taxotere side chains,” Grenoble Cedex, 1991. 

44

Thomas Mintjes 



Edward Knaven 

Cephalomannine is a natural product with a structure similar to the anti-cancer drug Paclitaxel. 

Paclitaxel is normally extracted from the bark of the tree Taxus Brevifolia. In this process the tree is killed 

and only a small amount of Paclitaxel can be extracted from the bark of this tree. A different species of 

Taxus, Taxus Baccata, also contains Paclitaxel, however in addition to the desired compound, different 

compounds are also extracted. One of these compounds is Cephalomannine. Cephalomannine also has 

cyto-toxic activity, but it’s lower than that of Paclitaxel. The aim of this project is to investigate a way to 

convert the unwanted Cephalomannine into Paclitaxel as well as synthesize analogues of Paclitaxel that 

have been proven to also have a high cytotoxic activity. 

[1] J. H. Johnson, R. T. Gallegher, D. Wang, and J. S. Juchum, "Methods and compositions for converting taxane 

amides to paclitaxel or other taxanes," ed: Google Patents, 2004. 

[2] Ojima, C. L. Fumero-Oderda, S. D. Kuduk, Z. Ma, F. Kirikae, and T. Kirikae, "Structure–activity relationship 

study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of 

macrophage-like cells," Bioorganic & Medicinal Chemistry, vol. 11, pp. 2867-2888, 7/3/ 2003. 

45

46

Willem Aarts 

ATGM academie voor Technologie Gezondheid en Milieu 


Dr. Sylvestre Bonnet and doctoral student Anja Busemann, University of Leiden 

With a view to creating ruthenium complexes with a potential application in the field of photodynamic therapy of 

cancer, certain appropriately functionalized terpyridine ligand were synthesized. We describe the synthesis of 

[2,2':6',2''-terpyridin]-4'-ylmethanol (3). The ligand was attempted to be synthesized in two different syntheses 

routes. In both cases, [2,2':6',2''-terpyridine]-4'-carboxylic acid (1) was used, which was obtained using a one-pot 

synthesis.[1] The first route, carboxylic acid (1) was reduced using lithium aluminium hydride in attempt to obtain 

the ligand 3.[2,3] Where in the second route, a Fischer esterification was performed on the carboxylic acid,[4] 

giving methyl [2,2':6',2''-terpyridine]-4'-carboxylate (2), followed by a reduction using sodium borohydride to 

obtain ligand 3.[5] The yield for the ligand 1 was 8%. For the reductions via both routes, no molecules have been 

characterized yet, due to the impurities. The synthesis of ligand 1 has been confirmed by 1H NMR, mass 

spectrometry and IR. 

Keywords: ruthenium • terpyridine ligands • multidentate ligands • photodynamic therapy 

[1] Stublla, A.; Potvin, P. G. Eur. J. Inorg. Chem. 2010, No. 19, 3040–3050. 

[2] Le, D. D.; Zhang, Y.; Chien, D. H.; Moravek, J. Journal of Labelled Compounds and Radiopharmaceuticals. 

2000, pp 1119–1125. 

[3] Hoover, J. M.; Stahl, S. S.; Carreira, E. M. Org. Synth. 2013, 90 (I), 240–250.Shinpuku, Y.; Inui, F.; Nakai, M.; 

Nakabayashi, Y. J. Photochem. Photobiol. A Chem. 2011, 222 (1), 203–209. 

[4] Heller, M.; Schubert, U. S. J. Org. Chem. 2002, 67 (23), 8269–8272 

47

Wouter Bierens 

ATGM academie voor Technologie Gezondheid en Milieu 


PDT (Photo Dynamic Treatment) is a cancer treatment specifically targeting the tumors by irradiating the tumors 

with light, this will activate the cytotoxic properties of a photo dynamic medicine. By radiating the tumor, only the 

tumor will be targeted which is an advantage over chemotherapy which will kill not only cancerous cells, but also 

the healthy cells. The complex [Ru(tpy)(bpy)Cl]2+ Bis(N-biotinyl)-3,6-dioxaoctane-1,8-diamine is a photo dynamic 

medicine. The biotin compound will bind with avidine receptors of tumor cells. When irradiated the biotin ligand 

on the ruthenium complex will be substituted by water which allows the rutheniumcomplex to attack the DNA of 

the cell. This research focuses on the synthesis of Bis(N-biotinyl)-3,6-dioxaoctane-1,8-diamine. By coupling the 

biotin molecule to diaminodioxoctane with a couplingagent through a two steps synthesis. Different 

couplingagents (Disuccinimidylcarbonate, COMU, HATU, DCI and DEPT) was compared to eachother in order to 

determine the best conversion. The crude product was purified with flash chromatography and analyzed with 

Hnmr and LC-MS. 

HN 

O 

S 

NH 

O 

OH 

O 

O 

O 

O 

O 

N 

O O 

N 

Et 3 

N 

DMF, RT, 16 uur 

O 

HN 

O 

S 

NH 

O 

O 

O 

N 

O 

N H 2 

O 

O 

Et 3 

N 

DMF, RT, 26 uur 

NH 2 

HN 

S 

NH 

O 

NH 

O 

O 

NH 

O 

HN 

S 

NH 

O 

[1] Synthesis of a biotin-functionalized ruthenium complex with a light-cleavable biotin moiety. Bianka Siewert, 

Michiel Langerman, Sylvestre Bonnet. unpublished results. 

[2] In vitro evaluation of ruthenium complexes for photodynamic therapy. Wenna Lia, Qiang Xieb, Linglin Laia, 

Zhentao Moa, Xiaofang Penga, Ennian Lenga, Dandan Zhanga, Hongxia Suna, Yiqi Lia, Wenjie Meic, Shuying 

Gaoa. Junie 2017, Photodiagnosis and Photodynamic Therapy, volume 18. 

[3] COMU: A Safer and More Effective Replacement for Benzotriazole-Based Uronium Coupling Reagents . El- 

Faham, A., et al. 15, Chemistry a European Journal, Vol. 2009, pp. 9404-9416. 

48

Jari Bos 

ATGM Academy of Technology Health and Environment 

Avans University, Breda 

Radboud University, Nijmegen 

Protein misfolding is a change of the three-dimensional form of a protein. What leads to a change in functionality. 

Sometimes misfolding can cause toxic proteins what can lead to elderly diseases like Alzheimer and Parkinson. [1] 

The Radboud University is IR folding of proteins in gas phase. For this, four dipeptides are made: carboxybenzilalanine-alanine-methyl 

ester, carboxybenzil-alanine-alanine-amide, acetyl-phenylalanine-alanine-methyl ester 

and acetyl-phenylalanine-alanine-amide. The two methyl ester dipeptides are synthesised with coupling agent 

COMU. Which has a high theoretical yield (99%). [2] The two methyl ester dipeptides are converted to the amide 

products by an ammonolysis with ammonium hydroxide. Al the dipeptides are purified by column chromatography 

and analysed by FTIR, LC-MS. 

[1] N. Bolshette, K. Thakur, A. Bidkar, C. Trandafir, P. Kumar en R. Gogoi, ‘’Protein folding and misfolding in the 

neurodegenerative disorders: A review,” Revue Neurologique , vol. 170, nr. 3, pp. 151-161, 2014. 

[2] A. El-Fahama en F. Albericio, ‘’COMU: A third generation of uronium-type coupling reagents,” journal of 

peptide science, vol. 16, nr. 1, pp. 6-9, 2009. 

49

Sem Goossens 



University Leiden 

Indole is a heterocyclic aromatic compound. It is a compound common in nature and is widely used in the 

pharmaceutical industry. [1] The indoles in this research will be used for synthesis cyanine dyes. The Indole 

derivatives will be connected with polymethine chains, the cyanine dyes will be Infrared active. The cyanine dyes 

are used in cancer research and has a function as label. Because of this, the cellular process can be followed, like 

medication that will arrive in tumors. [2] Indoles/cyanine dyes have a poor solubility in water, so it is badly 

absorbed in the human body. Therefore, there will be synthesized different indole derivatives with water-soluble 

side groups. Sulfonic acid is an example of a side group that will be used. The indole derivatives will be synthesized 

with the Fischer Indole synthesis, under acid conditions. [3] The purification will be done with column 

chromatography. The characterization will be done with H-NMR and FTIR. 

Keywords: Indole • Sulfonic acid • Cyanine Dyes • Fisher Indole Synthesis. 

[1] G. W. Gribble, Tetrahedron Organic Chemistry Series, Volume 20, 2000, p. 73 – 75. 

[2] S. Luo et al., “A review of NIR dyes in cancer targeting and imaging,” Journal of Biomaterials, vol. 32, 2011, p. 

7127-7138 

[3] D. J. Kim e.a., Novel Cyanine Dyes with Vinylsulfone Group for Labeling Biomolecules, Bioconjugate 

Chemistry, Korea 

50

Fabian van Acker 

ATGM Academy of Technology, Health and Environment 


Lies Bouwman 

1,2,4,5-tetrakis(broommethyl)benzene in this research is used to synthezise ligand for metal complexes. About 

the substance itself is little known but the reaction mechanism which we see in the table of content and which is 

described by J. Verhagen could be synthesized a ligand with the substance. With the ligand we can create metal 

complexes that can be used for hydrogenase as a replacement for enzymes. [1] The purpose of this research is to 

see if the expected ligand can actually be synthesized and whether the return achieved by J. Verhagen and S. 

Verbeek could be matched to their research. [2] The expected yield will be around 80% with a 10% deviation. In 

addition the metal complex will be synthesized by S. Verbeek in Leiden and researched which properties the 

complex has. [3] 

[1] Verhagen, J. A. W.; Beretta, M.; Spek, A. L.; Bouwman, E. Inorg. Chim. Acta 2004, 357 (9), 2687–2693 

[2] Verhagen, J. A. W.; Ellis, D. D.; Lutz, M.; Spek, A. L.; Bouwman, E. J. Chem. Soc. Dalt. Trans. 2002, Nr. 7, 

1275–1280. 

[3] Verbeek, S. 2016. Unpublished results. 

51

Cas van Deursen 

ATGM Academy of Technology, Health and Environment 

Avans Hogeschool Breda 

Paula Contreras Carballada, Anouk Rijs 

In dit onderzoek zijn N-carboxybenzyl-L-alanine-L-alanine-methylester (Z-ala-ala-OMe), N-carboxybenzyl-Lalanine-L-alanine 

(Z-ala-ala), N-acetyl-L-phenylalanine-L-alanine-methylester (Ac-phe-ala-OMe) en N-acetylphenylalanine-L-alanine 

(Ac-phe-ala) gesynthetiseerd, opgezuiverd en geanalyseerd voor verder onderzoek naar 

de stapeling van deze dipeptiden. Z-ala-ala-OMe is gesynthetiseerd door N-carboxybenzyl-L-alanine, L-Alaninemethylester, 

N,N-Diisopropylethylamine en COMU samen te voegen en gedurende 2 uur te roeren bij 

kamertemperatuur. Ac-phe-Ala-OMe is gesynthetiseerd op dezelfde wijze, waarbij de Z-ala werd vervangen door 

Ac-phe. Z-ala-ala en Ac-phe-ala werden verkregen door Z-ala-ala-OMe en Ac-phe-ala-OMe te hydrolyseren met 

LiOH. De verkregen producten werden gekarakteriseerd met behulp van FTIR en opgezuiverd met behulp van een 

silicakolom. De opgezuiverde producten zijn vervolgens met LC/MS onderzocht om verontreinigingen uit te 

sluiten. De opbrengst van de syntheses van Z-ala-ala-OMe, Z-ala-ala, Ac-phe-ala-OMe en Ac-phe-ala waren 

respectievelijk 78, 90, 74 en 91%. Er word aangeraden om de syntheses van Z-ala-ala-OMe en Ac-phe-ala-OMe 

gedurende 6 i.p.v. 2 uur te laten lopen om op deze manier een hogere opbrengst te behalen. 

[1] Volledig: (1-[1-(cyano-2-ethoxy-2-oxoethylideen-aminooxy)-dimethylamino-morpholino]-uronium 

heafluorofosfaat 

52

Koen Segers, Avans Hogeschool, SPOC groep 6, 2017, Paula Contreras Carballada 

The folding of proteins from linear amino-acid sequences into active three-dimensional structures is a process 

essential for exhibiting protein functionality such as, catalysis, ligand binding and signal transduction. When 

proteins fail to fold correctly, misfolding occurs which can yield inactive proteins but in some cases may result in 

an aggregation of proteins with toxic properties. The misfolding and associated aggregation of proteins in the 

human body is a characteristic feature of numerous neurodegenerative diseases including Alzheimer’s, 

Parkinson’s, and ALS. Understanding the underlying mechanisms of protein folding and misfolding is of great 

importance of curing earlier named diseases. [1] 

The Molecular and Biophysics group of FELIX (free electron laser 

laboratory) performs studies on peptide aggregation. [2] Four 

dipeptides were chosen as model compounds, Z-Ala-Ala-OMe 

(1), Ac-Phe-Ala-OMe (2), Z-Ala-Ala-NHMe (3) and Ac-Phe-Ala- 

NHMe (4), see structures below. This project aims to synthesize 

pure samples of dipeptides by using a novel coupling agent 

COMU, in order to optimize yield, safety and cost compared to 

HATU coupling. [3] Further purification of synthesis products is 

done by column chromatography, fractions are characterized by 

LC-MS. 

Figure 1 - The four model peptides chosen for IR-folding studies 

Keywords: Protein Folding • Peptide synthesis • COMU coupling • LC-MS 

The general reaction mechanism for the synthesis of a dipeptide with COMU coupling and DIPEA is shown in figure 

2. In this project, the R1-group is Z-Ala or Ac-Phe and the R2-group is Ala-Ome. After deprotonation of the peptide 

by DIPEA, A nucleophilic oxygen is formed on the amino acid which attacks the carbocation on the COMU coupling 

agent. The nucleophilic oxygen on the resulting deprotonated Oxyma group attacks on the carbonyl of the amino 

acid/morpholino intermediate, pushing the morpholino group off. This is followed by the formation of the peptide 

coupled to Oxyma pure. A deprotonated amino acid then attacks the carbonyl of Z-ala/Oxyma pure to produce 

the coupled amino acids. 

Figure 2 - General reaction mechanism of a dipeptide synthesis utilizing COMU as coupling agent 

[1] M. Stefani and C. M. Dobson, "Protein aggregation and aggregate toxicity: new insights into protein folding, 

misfolding diseases and biological evolution," J. Mol. Med., 2003. 

[2] A. M. Rijs, "Gas-Phase IR-spectroscopy and structure of biological molecules," Topics in Current Chemistry. 

2015 

[3] A. El-Fahman, "COMU: A Safer and More Effective Replacement for Benzotriazole-Based Uronium Coupling 

Reagent," Chem. Eur. J., 2009 

53

54

Dear readers, 

After a lot of planning, experiments, setbacks and joys, the minor SPOC 2016-2017 has come 

to an end. The results of this hard work are presented at the SPOC Poster Presentation to 

which this Book of Abstracts is an inseparable part. We have learned a lot during this minor, 

both professionally as well as personally and for their help we have to thank all contributors 

who helped in the successful completion of the projects during the past 20 weeks. 

Firstly, we would like to thank the accompanying teachers: Sonny van Seeters, Kees Kruithof, 

Jack van Schijndel, Nishant Sewgobind, Paula Contreras-Carballada and Erik Rump for their 

great guidance, nudges in the right direction and feedback. Without your guidance, it 

wouldn’t have been possible to achieve the same level of quality in the completion of our 

projects. 

Furthermore, we want to thank the technical staff; Frank Luijkx, Frank Welling, Cynthia van 

den Berg, Laura van de Corput-Mensen, Marieke Tellekamp, Koen van Beurden, Thomas 

Ravensbergen and Dennis Molendijk for their support during the implementation of the 

projects and help with difficulties in the lab. A very special thank you goes to Edward Knaven 

for his efforts to analyze our synthetic compounds with LC-MS. Also, we would like to thank 

Annemarie Zweedijk-Thijssen for the ordering of chemicals and Anita Konings for the always 

clean glassware. 

Last but not least, we want to thank the research project providers for very interesting project 

topics and their critical view on the results. 

Without these people SPOC 2016-2017 wouldn’t have been the same. 

With kind regards, 

The students of SPOC 2016-2017 

55

56

v.l.n.r.: Paula, Annabelle, Justin, Koen 

57

58

Book of Abstracts, SPOC 2017

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