Book of abstracts version 5

Book of Abstracts 

Poster presentations 

Specialization/Minor: 

Polymer and Organic chemistry 

2018 

1 

ATGM – Academy for Technology of Health and Environment

2

Avans University of Applied Sciences 

Lovensdijkstraat 61-63 

4818 AJ Breda 

Postbus 90.116, 4800 RA Breda 

Reception 088-5257500 

3

4

Collaborations 

5

6

Preface 

Dear reader, 

We present here the Book of Abstracts for the SPOC (Specialisation Polymer and 

Organic Chemistry) minor from ATGM (The Academy for Technology of Health and 

Environment) of Avans Hogeschool in Breda. 

In this book of abstracts you can find a brief description of the 39 research projects 

that are currently being carried out by the candidates to specialize in Polymer and 

Organic Chemistry. The topics of research span for the green synthesis of monomers 

for biobased-polymers or the application of new polymerization techniques, to the 

synthesis of building blocks or scaffolds for new (anti-cancer) medicines, revisiting of 

the Knoevenagel reaction, and a lot more interesting topics. 

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 28 th 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 presentations and this Book of Abstracts and we hope 

to be able to welcome you on June 28 th . 

Yours sincerely, 

Egor Silin, Ian Bouwmeester, Neline van Loon and Paula Contreras Carballada 

The Book of Abstracts Committee 

7

8

Index 

SPOC1 13 

Tutor: Nishant Sewgobind, MSc 

SPOC2 23 

Tutor: Kees Kruithof, Phd 

SPOC3 31 

Tutor: Betty Oostenbrink, MSc 

SPOC4 38 

Tutor: Jack van Schijndel, MSc 

SPOC5 48 

Tutor: Sonny van Seeters, MSc 

SPOC6 57 

Tutor: Erik Rump, Phd 

SPOC7 65 

Tutor: Paula Contreras Carballada, Phd 

Acknowledgements 73 

9

10

Group index 

SPOC1 

The inhibition of the Pseudomonas Auruginosa bacteria. 

Mariët Bakker 

The multivalent inhibition of bacterial lectins. 

Louis Honselaar 

Synthesis of a surface-active RAFT-agent 4- 

thiobenzylsulfanylmethylbenzoate. 

Rashimi Garib 

Synthesis of 2-cyano-2-propyl benzodithioate. 

Joyce Amijs 

Synthesis for a building block for thiodigalactoside. 

Arjan de Smit 

Synthesis for a building block for thiodigalactoside 

building blocks, towards anti-cancer or anti-inflammatory 

drugs. 

Thijs Verdaasdonk 

11

12

The inhibition of the Pseudomonas Aeruginosa bacteria 

Author 

Mariët Bakker 

Academy of Technology for Health and Environment 

Avans Hogeschool, Breda 

Universiteit Utrecht 

Nishant Sewgobind 

Abstract 

The bacterial adhesion lectin LecA is an attractive target for the interference with the infectivity of its producer 

Pseudomonas Aeruginosa.[1] Divalent ligands with two terminal galactoside moieties were shown to be potent inhibitors. 

In hopes of further enhancing the LecA inhibitory, a divalent galactoside ligand will be expanded to a quadrupole 

galactoside ligand, as shown in Figure 1. The linking between two divalent galactosides takes place through a PEG - 

coupling molecule (8). [2] 

In this research, the starting material for synthesizing the PEG-molecule is 1,4-dimethoxybenzene(2). The synthesis route 

is shown in Figure 2. The first step is the halogenation of 1,4 -dimethoxybenzene(2). After the synthesis of 2,5-diiodo-1,4- 

dimethoxybenzene(4), the product has reacted with a [TMAH][Al 2Cl 7] complex to replace a methoxide group for a 

hydroxyl group. The third step is the synthesis of ditosyl tetraethylenegycol( 7), which can react with the demethylated 

phenol(4) to form the PEG coupling molecule called 2,5-diiodo-4-methoxyphenol. The reactions were followed with TLC 

and the products were analyzed by FTIR and HNMR. 

Keywords: LecA, Pseudomonas Aeruginosa, PEG, halogenation, demethylation 

Table of content 

Figure 1: Two divalent galactosides are coupled by a PEG. Figure 2: The synthesis routes in this research. 

[1] Novoa, Alexandre. Eierhoff, Thorsten. Topin, Jérémie. “A LecA Ligand Identified from a Galactoside-Conjugate Array 

Inhibits Host Cell Invasion by Pseudomonas aeruginosa”. Angewandte Chemie. (2014) 

[2] Bouvier, Benjamin. “Optimizing the multivalent binding of bacterial Lectin LecA by glycopeptide dendrimers for 

therapeutic purposes”. Journal of Chemical information and modelling, ACS publications (2016) 

13

The multivalent inhibition of bacterial lectins 

Author 

The multivalent inhibition of bacterial lectins 

Louis Honselaar 





Abstract 

The bacterial binding lectin LecA is a beneficial target to prevent the presence of the bacterium P.aeruginosa to its host. 

The study of Ou Fu et al. [1] has shown that divalent ligands with two terminal galactoside variants associated with 

alternating glucose- triazole spacers are very effective inhibitors. This molecule also proved to have good solubility in 

water and it appeared that three triazole spacers were the optimal length for LecA inhibition. In this study, positively 

charged, negatively charged and lipophilic ligands were tested although these are good LecA ligands, no improved binding 

to LecA can be seen.In this research a molecule is synthesized that can be synthesized with a tetravalent inhibitor. This 

could help with the anti-infection properties of the ligand. Figure 1 shows the tetravalent molecule. The reaction overview 

is shown in figure 2. The aim of this research project is to synthesize (7) tetraethylene glycol di (2,5 -diiodo-4- 

methoxybenzene 

The multivalent 

with (5) 4-methoxyphenol 

inhibition 

as the starting 

of 

product. 

bacterial 

The final product 

lectins 

(7) is a precurser for the synthesis 

of the tetravalent inhibitor (2). The analyzes used for the fastening of products and the final product are TLC, FTIR and 1H - 

NMR, and the conversion at each synthesis step. 

Keywords: LecA, P. aeruginosa, divalent ligand, tetravalent ligand 


Figure 1 : Reaction overview fort he synthesis of 

tetraethylene glycol di(2,5-diiodo-4-methoxyphenoll. 

[1] A. V. P. H. C. Q. v. U. J. K. N. J. d. M. R. J. P. Ou Fu, „Functionalization of a Rigid Divalent Ligand for LecA, a Bacterial 

Adhesion Lectin,” ChemPubSoc Europe, pp. 463-470, 2015. 

14 

Figure 2: LecA inhibitor.

Synthesis of a surface-active RAFT-agent 4-thiobenzyl 

sulfanylmethyl benzoate 

hesis of a surface-active RAFT-agent 4-thiobenzyl sulfanylmethyl benzoa 

Author 

Rashmi Garib 

Academy Synthesis of Technology for of Health a surface-active and Environment RAFT-agent 4-thiobenzyl 


sulfanylmethyl benzoate 

Sonny van Seeters 


Abstract 

In this study, a surface-active RAFT-agent, 4-thiobenzoyl sulfanylmethyl benzoate, was synthesized and characterized for 

further emulsion polymerization (figure 1). RAFT-agents are very expensive and hard to purify. They can be used at a large 

scale of monomers, including determination of molecular weight. A surface active RAFT-agent is partially polair and 

partially apolair, this way it is easier to polymerize a block copolymer instead of using a normal RAFT-agent. After 

synthesizing it is expected to have similar characteristics in H 1 -NMR spectrum [1] (figure 2). 

The first step is the attack of the Grignard reagent with carbon disulfide in dry THF and under dry conditions. Second is 

adding 2:1 molar ratio to the synthesized magnesium benzodithioate bromide and 4 -(bromomethyl)benzoate acid. After 

these steps, the unreacted reagents were removed by distillation under pressure[2] . L/L-extraction with acidified water of 

a pH level between 1-2, MTBE and 1M NaOH to deprotonate[3]. The product was characterized with LC -MS and H 1 -NMR. 

Keywords: RAFT-agent, living radical polymerization 


Figure 4: Reaction scheme of the synthesis of 4-thiobenzoyl sulfanylmethyl 

benzoate. 

Figure 3: H 1 -NMR spectrum of synthesized 

product. 

[1] H. Lee, S. E. Shim, H. Jung en S. Choe, „Poly(methyl methacrylate) Latex Prepared by living free radical Emulsion 

polymerization using a sufrace active iniferter (Suriniferter) and its properties,” Applied Chemistery, may 2003 

[2] S. E. Shim, H. Jung, H. Lee, J. Biswas en S. Choe, „Living radical dispersion photopolymerization of styrene by a 

reversible addition - fragmentation chain transfer (RAFT) agent,” Polymer, vol. 2003, nr. 14 july, p. 10, 2003. 

[3] Y. K. Chong, K. Julia, T. P. T. Le, G. Moad, A. Postma, E. Rizzardo en S. H. Thang, „Thiocarbonylthio Compounds 

[S=C(Ph)S-R] in Free Radical Polymerization with Reversible Addition-Fragmentation Chain Transfer (RAFT Polymerization). 

Role of the Free-Radical Leaving Group (R),” p. 17, 16 December 2002. 

15

Synthesis of 2-cyano-2-propyl benzodithioate. 

Synthesis of 2-cyano-2-propyl benzodithioate 

Author 

Joyce Amijs 





Abstract 

Reversible Addition Fragmentation Chain Transfer (RAFT) polymerization is a controlled/living radi cal polymerization. This 

polymerization method is used for the synthesis of styrene and acrylate block copolymers[1]. The RAFT-agent 2-cyano-2- 

propyl benzodithioate that is used for this polymerization is very expensive, so it is important to synthesize th e agent and 

save some cost. It is also important to synthesize the RAFT-agent so it can be used for practical assignments at school, 

especially for emulsion polymerization. Previous research showed that the yield of the RAFT-agent is less than 1%, so the 

goal of this study is to optimize the synthesis of RAFT-agent 2-cyano-2-propyl benzodithioate[2]. The synthesis of 2-cyano- 

2-propyl benzodithioate is a multiple step reaction and is shown in Figure 1. First dithiobenzoate (2) is synthesized from 

phenylmagnesiumbromide (1), carbondisulfide and hydrochloric acid. Second bis(thiobenzoyl)disulfide (3) is synthesized 

according a redox reaction. This step will be optimized and at least it must give a 10% higher yield by using methyl tert - 

butyl ether and ethanol as solvent instead of ethanol. The RAFT-agent (4) is synthesized with azobisisobutyronitrile and 

the product of this synthesis will be purified with column chromatography. The products 3 and 4 will be analyzed with UV - 

Vis spectroscopy, FTIR and LC-MS. 

Keywords: RAFT-agent, 2-cyano-2-propyl benzodithioate, dithiobenzoate, bis(thiobenzoyl)disulfide 


Figure 1. Reaction equation of 2-cyano-2-propyl benzodithioate. 

[1] M. Hillmyer, „Block copolymer synthesis,” Current opinion in solid state and materials science, vol. 4, nr. 6, pp. 559- 

564, 1999. 

[2] B. Koumba en A. Mayelle, „Design, synthesis and characterization of novel raft agents,” University of stellenbosch, 

Stellenbosch, 2005. 

16

Synthesis for a building block for thiodigalactoside 

Author 

Arjan Synthesis de Smit for a building block for thiodigalactoside 





Abstract 

Multiple galectins have been found in the human body and are involved with biological processes like mitosis and the 

survival of tumor cells. The 14 different galectins can be divided into three subgroups. The first group has one 

carbohydrate-recognition domain (CRD). The second group also has a proline and glycine rich fragment and the last group 

has two CRD’s. Galactin-3 is the only protein that fits into the second subgroup. [1] The goal of this research is to make 3 - 

O-acetyl-1,2;5,6-di-O-isopropylidene-α-D-gulofuranose from 1,2;5,6-di-O-isopropylidene-α-D-glucofuranose in three 

synthesis. This product can be used as a building block for a thiodigalactoside that has a strong affinity with galectin -3, but 

not with the other proteins. It is expected that the conversion rate of each reaction step, shown in the table of content, 

will be 70% or higher. The first reaction used is an oxidation with pyridinium dichromate. This reaction is followed by an 

acetylation with pyridine and acetic anhydride. The product is formed after hydrogenation with palladium on carbon. [2] 

The reactions can be follow with TLC and the intermediates and product can be analysed with FT-IR and NMR after 

purification with column chromatography. 

Keywords: Medicinal chemistry, galectins, thiodigalactoside, galectin-3 


Figure 5: Reaction scheme for the synthesis of 1,2;5,6-di-O-isopropylidine-α-D-gulofuranose from 1,2;5,6-di-Oisopropylidene-α-D-glucofuranose. 

[1] H. van Hattum, H. M. Branderhorst, E. E. Moret, U. J. Nilsson, H. Leffler en R. J. Pieters, „Tuning the Preference of 

Thiodigalactoside- and Lactosamine-Based Ligands to Galectin-3 over Galectin-1,” Journal of Medicinal Chemistry, vol. 56, 

nr. 3, pp. 1350-1354, 2013. 

[2] J. Elhalabi en K. G. Rice, „Synthesis of Uridine 5'-[2-S-Pyridyl-3-thio-alpha-D-galactopyranosyl Diphospate]: Precursors 

of UDP-Thiogal Sugar Nucleotide Donor Substrate for béta-1,4-Galactosyltransferase,” Nucleosides, Nucleotides & Nucleic 

Acids, vol. 23, nr1, pp. 195-205, 2004 

17

Synthesis thiodigalactoside building blocks, towards anticancer 

or anti-inflammatory drugs. 

Author 

Thijs Verdaasdonk 





Abstract 

Between all the proteins galectin is defined by its affinity for β-galactoside. Galectins function intracellularly, 

extracellularly and they are involved in a range of biological processes. Many of these processes are beneficial f or a 

person’s health but these proteins also play a role in some pathological processes. Despite all this the exact biological rol e 

of galectins remains questionable. For further research an inhibitor is needed to be able to conduct experiments with 

these galectins. [1] The inhibitor is a thiodigalactoside molecule wherefor the basic building block a β -galactoside namely 

3-O-acetyl-1,2;5,6-di-O-isopropylidene-α-D-gulofuranose(4) will be synthesized from 1,2,5,6 -diacetone-α-Dglucofuranose(1). 

The complete synthesis will be displayed in the table of content(figure 1) it consists of 3 steps with an 

expected conversion rate of 70%. The first step is a oxidation with pyridinium dichromate, this product will be acetylated 

with DABCO and acetic anhydride and the final step is a hydrogenation using palladium on carbon. All products are 

purified by column chromatography and analysed with TLC, H -NMR and FTIR.[2] 

Keywords: Thiodigalactoside, galectin, inhibitor, β-galactoside and Diacetone-D-glucose. 


Figure 1: reaction scheme full synthesis from 1,2,5,6-diacetone-α-D-glucofuranose(1) to 3-O-acetyl-1,2;5,6-di-Oisopropylidene-α-D-gulofuranose(4). 

[1] S. Karger, „The Role of Galectin-3 as a Marker of Cancer and inflammation in a stage IV Ovarian Cancer Patient with 

Underlying Pro-Inflammatory Comorbidities,” Case reports in oncology, nr. 6, pp. 343 -349, 2013. 

[2] H. van Hattum en e. all., „Tuning the Preference of Thiodigalactoside- and Lactosamine-Based,” Journal of Medicinal 

Chemistry, nr. 56, pp. 1350-1354, 2013. 

18

19

20

Group index 

SPOC2 

In situ catalysed Green Knoevenagel synthesis of novel 

3,4-unsubstituted Courmarin analogues 

Sjoerd van der Gun 

Synthesis of coumarin derivatives and Ea determination 

Max van Liesdonk 

Determination of activation energies of 3,4-unsubstituded 

coumarine synthesis using the green Knoevenagel 

condensation 

Maudy Robben 

Synthesis of biobased monomers 

Natasja Bos 

Synthesis and purification of bio-based monomers 

Keanu Manders 

21

22

Book of abstracts SPOC 2018 

3,4-unsubstituted Coumarin analogues 

Author 

Knoevenagel synthesis of novel 

marin analogues 

Sjoerd van der Gun 



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. 


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 

23

Synthesis of coumarin derivatives and E a determination 

Autor 

Max van Liesdonk 





oumarin derivatives and E a determination 

Abstract 

The goal of this research is to determine what the activation energy of the synthesis of coumarin derivatives by using the 

Green Knoevenagel Condensatie. The molecules that will be synthesized in this project are 3 -carboxycoumarin and 3- 

carboxy-6-methylcourmarin. A second goal is to determine the difference in activation energy when using different types 

of katalysts, which are ammonium bicarbonate and piperidine. To determine the reaction rate constant (k) rate every 

different reaction is done under 2 different temperatures. All together giving a total of 8 reactions that have to be 

followed in time by taking samples. From these samples the concentration of the reactants and product are determined. 

The gathered information can then be used to calculate the k form there the E a is calculated. 

Expectations for these experiments will be that the use of ammonium bicarbonate will give a lower activation energy then 

piperidine. 

Using the Green Knoevenagel reaction gives a mechanism which contains whats called a katalitic intermediair. The third 

goal is comparing the E a of the syntheses by using ammonium bicarbonate or the pre-synthesized katalytic intermediair to 

make 3-carboxycoumarin. 

The used method for synthesizing these components is adding salicylaldehyde, malonic acid and a catalyst in a reactor 

and let it stir for 1 hour at 90°C [1][2][3]. 

Keywords: Green Knoevenagel Condensation, katalytic intermediair, coumarin, activation energy, reaction rate constant 


Figure 1: The Green Knoevenagel reaction how it is used in this research project. 

[1] Temperature dependent green synthesis of 3-carboxycoumarins and 3,4- unisubstituted coumarins, 2018. 

[2] Mechanistic insight in the green knoevenagel reaction of furanic aldehydes using ammoniums salts as catalyst, 2018 

[3] Chemical kinetics, 2017 

24

Determination of activation energies of 3,4-unsubstituded 

coumarine synthesis using the green Knoevenagel condensation 

Autor 

Maudy Robben 

f coumarin derivatives and E a determination 





Abstract 

Coumarins are heterocyclic aromatic compounds and can be obtained naturally or synthetically. One of the synthesis 

routes to obtain coumarins is the solvent-free green Knoevenagel condensation[1]. The purpose of this research was to 

synthesize two 3,4-unsubstituded coumarins (standard coumarin and 6-carboxycoumarin) out of hydroxybenzaldehydes 

(2-hydroxybenzaldehyde and 2-hydroxy-5-methoxybenzaldehyde) (Figure 1). In this reactions was malonic acid and 

ammonium bicarbonate or piperidine used. Of all these synthesis, was the activation energy determined by carrying out 

the reaction to carboxycoumarins at 70⁰C and 90⁰C during 60 minutes. The carboxycoumarins were decarboxylated by 

heating the mixture during 120 minutes at a temperature of 140⁰C. The determined activation energies have been 

compared. As a side study has the catalytic intermediate (Figure 2) of the reaction between 2 -hydroxybenzaldehyde and 

ammonium bicarbonate been synthesized by heating those substances during 30 minutes at 50⁰C. The intermediate has 

been precipitated in a 30% ammonia solution. In co-operation with a research group at Avans is a comparison made 

between the activation energy of the reaction where the catalytic intermediate has been formed during the reaction and 

between the activation energy of the reaction where the catalytic intermediate has been formed previously. All products 

have been analysed by TLC, IR, NMR, melting point determination and HPLC. 

Keywords: Coumarin, green Knoevenagel condensation, catalytic intermediate 


Figure 1: Reaction equation of the coumarin synthesis . 

Figure 2: Catalitic intermediate. 

[1] J. van Schijndel, D. Molendijk, L. A. Canalle, E. T. Rump en J. Meuldijk, „Temperature Dependent Green Synthesis of 3 - 

Carboxycoumarins and 3,4-unsubstituded Coumarins,” Bentham Science, p. 6, 2017. 

25

Synthesis of biobased monomers 


Autor 

Natasja Bos 



University of Maastricht 

iobased monomers 

Abstract 

In collaboration with the Biobased Materials group at the University of Maastricht, research is being conducted into the 

synthesis, processing and use of biobased monomers. This involves working with renewable itaconic acid and various 

diamines and thereby forming a monomer. The goal is to make the monomer three times with itaconic acid and using 

different diamines. The main focus here is to reprocess the monomer. This caused problems at the University of 

Maastricht. 

Several monomers have been synthesized with ethylenediamine, 1,4 -butenediamine and 1,7-heptanediamine (reaction 

scheme (fig. 1) according to the method of F. Ayadi et al [1] and worked up in different ways. This is done by traditional 

recrystallization with different solvent compositions of water and methanol. A vapor diffusion [2] crystallization has also 

been performed (fig. 2). All crystallizations are placed in the refrigerator to start crystallizatio n. Crystals have been formed 

and will be analyzed with DSC and FTIR. 

Keywords: Renewable, Itaconic acid, crystallisation 


Figure 1: Reaction scheme. 

Figure 2: Vapour Diffusion setup. 

[1] F. Ayadi, „Synthese van bis(pyrrolidone-4-carboxyloc acid),” Polymer Journal, 2013. 

[2] MIT, „Growing quality crystals,” [Online]. Available: http://web.mit.edu /x-ray/cystallize.html. [Opened 27 Februari 

2018] 

26


Synthesis and purification of bio-based monomers 

Author 

Keanu Manders 



University of Maastricht 

purification of bio-based monomers 

Abstract 

The synthesis of bio-based polymers is a growing subject, not only due to their green qualities, but also because they have 

better physical characteristics compared to other plastics. With the combination of itaconic acid and a diamine, 

Maastricht University, formed a bio-degradable monomer (fig 1.) The possibility to apply variation in the chain length (n) 

of the diamine, gives the molecule the ability to form a monomer with great variation of chain lengths. The challenging 

part of this research is however the purification of the molecule. When the chain length is varied, the yield of the target 

molecule decreases. The objective of this research is finding the most efficient way to synthesize and purify the monomer. 

It is expected that when a more efficient method is determined a yield of 85% is possible for t he most difficult chain 

lengths [1]. However the presence of chiral centrums in the molecule could complicate the purification. To determine the 

purity of the molecule DSC will be used to compare the Tg (˚C), Tm (˚C) and Td (˚C) with previous found results. The 

molecule will be synthesized via a Michael addition. Three different diamines (1,4 -diaminobutane; ethylenediamine; 1,5- 

diaminopropane) are used as starting reactants. In the presence o f water, itaconic acid will react via the Michael addition 

to form the desired monomer [2]. The next step is then to purify the molecule via different methods such as 

recrystallization in 50%/50% methanol water; vapor diffusion recrystallization or column chromatography [3]. 

When the purity is satisfactory a final analysis of the product will happen at Maastricht University via NMR. 

Keywords: Bio-based, Bio-degradable monomer, diamines, Michael addition, recrystallization, purification 


Figure 1: The different target molecules using multiple diamines (1= ethylenediamine (n=2); 2= 1,4 -diaminobutane (n=4); 

3=1,5-diaminopropane (n=5)). 

Figure 2: The reaction equation of the monomer (1) and the polymerization of the monomer (2); with n for chain length 

and m for the number of monomers. 

[1] Roy, M., Noordzij, G. J., van den Boomen, Y., Rastogi, S., & Wilsens, C. H. (2018). Renewable (Bis) pyrrolidone Based 

Monomers as Components for Thermally Curable and Enzymatically Depolymerizable 2 -Oxazoline Thermoset Resins. ACS 

Sustainable Chemistry & Engineering, 6(4), 5053-5066. 

[2] Ayadi, F., Mamzed, S., Portella, C., & Dole, P. (2013). Synthesis of bis (pyrrolidone-4-carboxylic acid)-based polyamides 

derived from renewable itaconic acid—application as a compatibilizer in biopolymer blends. Polymer journal, 45(7), 766. 

[3] "Growing quality crystals," MIT Departement of Chemistry X -ray diffraction Facility, [Online]. Available: 

http://web.mit.edu /x-ray/cystallize.html. [Accessed 07 02 2018]. 

27

28

Group index 

SPOC3 

Decarboxylation of ferulic acid to green styrene-like 

monomer 

Finn Adema 

Synthesis of Poly(Glycerol Succinate – Co – Maleate) PLA 

enhancer 1 

Jacoline van Es 

Synthesis of Poly(Glycerol Succinate – Co – Maleate) PLA 

enhancer 2 

Wim van der Pluijm 

Biobased Polyesters From Ferulic Acid Derivatives 

Robin van den Kieboom 

Synthesis of a biobased and biodegradable “Super 

Absortbent Polymer” 

Fabian van Acker 

29

30

Decarboxylation of ferulic acid to green styrene-like monomer 

Decarboxylation of ferulic acid to green styrene-like monomer 

Author 

Finn Adema 




Abstract 

Polystyrene is a commonly used polymer, but fossil fuels are used for the production of styrene. A lot of research is done 

to find a green alternative, such as lignin. Lignin comes from trees and can be broken down to ferulic acid. Ferulic acid can 

be synthesized to a green styrene-like monomer (figure 1), which will be covered in this project. 

The goal is to optimize the decarboxylation of ferulic acid to 4 -vinylguaiacol, inclusive a high yield and purity. The method 

must also be reliable, scalable and easy to perform. According Yong [1] and Cadot [2], the best conditions are with a 

copper complex in dried glassware under nitrogen atmosphere. Kuipers [3] however, found out that a base works better 

and quicker for the decarboxylation of ferulic acid. This method consist 5 mmol ferulic acid with 10% HMTA and copper 

iodide. Copper doesn’t contribute to the reaction, but stabilize the product, according to Kuipers. 

Currently a Design of Experiments was performed to optimize the reaction conditions. In a half fractional design of 2 

levels (low, high), HMTA (0, 0.5 mmol), copper iodide (0, 0.5 mmol), glassware (dry, wet) and atmosphere (air, nitrogen) 

were tested. HMTA is a strong positive effect on the reaction, with dry glassware and nitrogen atmosphere as other 

positive effect. Copper iodide has a negative effect on the reaction, because the yield and purity were lower than without 

copper iodide. Also the reaction time is longer with copper iodide. Another effect on the reaction, which was tested apart, 

was the temperature. The best result was at 130°C, with almost the same amount of byproducts 

Keywords: Decarboxylation, ferulic acid, styrene, DoE 


Figure 7: Reaction of ferulic acid to 4-vinylguaiacol. 

Figure 8: DoE effect on purity 

[1] Yong, Z. (2013). CuI/1,10-phen/PEG promoted decarboxylation of 2,3-diarylacrylic acids. Org. Biomol. Chem., 11, 6967– 

6974. 

[2] Cadot, S. (2014). Preparation of functional styrenes from biosourced carboxylic acids by copper catalyzed 

decarboxylation in PEG. Green Chem., 16, 3089-3097. 

[3] Kuipers, F. (2018). De optimalisatie van de Groene Knoevenagel met als doel productie van biobased styreen -analogen. 

Avans Hogescholen Breda. 

31

Synthesis of Poly(Glycerol Succinate – Co – Maleate) PLA enhancer 1 

Synthesis of Poly(Glycerol Succinate – Co – Maleate) PLA enhanc 

Author 

Jacoline van Es 




Synthesis of Poly(Glycerol Succinate-Co-Maleate): PLA enhancer 

Abstract 

We use polymers every day, but most of them come from oil sources. There are now researches going on to recycle 

polymers and get them from biobased sources, for example from trees. A complex present in trees which is known as 

lignin, can be broken down to sinapic acid. Sinapic acid can be converted to styrene-like monomers (figure 1), which is 

proved by this project. 

The goal of this project was to optimize the decarboxylation of sinapic acid to canalol, which included a high yield and 

purity. The hypothesis was that this would be the best with a metal-ligand complex, with dry glassware in a nitrogen 

environment [1] [2].The standard procedure was with copper idone and HMTA in 0,025 mol% to sinapic acid at 115 ⁰C [. 

To find the best circumstances, we first tested the influence of water and oxygen by the standard procedure. 

The next step was a full factorial design, which tested 3 factors (low and high): temperature (100 ⁰C; 130⁰C), copper iodine 

(0; 0,05) and HMTA (0; 0,05). As center point we took the standard procedure. 

It is found that water, oxygen and copper iodine have a negative influence on the purity and yield. HMTA and 

temperature are positive for purity and yield, between the given ranges, which is sh own in figure 2. 

Keywords: Decarboxylation, Bioabased monomers, DoE 


Figure 9: Decarboxylation from sinapic acid 

to canalol. 

Figure 10: Result DoE: influence of head factors. 

[1] S. Cadot, „Preparation of functional styrene,” Green chemistry, vol. 16, 2014. 

[2] Y. Zou, „CuI/1,10-ogeb/PEG decarboxylation of 2,3 diarylacrylic acids,” organic and biomolecular chemistry, nr. 11, pp. 

6967-6975, 2013 

[3] L. Nijsen, „Synthesis, pufification and polymerisation of various biobased styrene derivates,” Avans Journal of Talents. 

32


Synthesis of Poly(Glycerol Succinate – Co – Maleate) PLA enhancer 2 

Author 

oly(Glycerol Wim van der Pluijm Succinate – Co – Maleate) PLA enhancer 2 



Abstract 

Using fossil fuels to create plastics bring many disadvantages, both the production and products created are harmful to 

the environment. Because of this many replacements are currently being explored. One of such replacements is the use of 

bio-degradable polymers, their range of use however is very limited because of their physical properties. Luckily it is 

possible to enhance the properties of these polymers to increase their range of use by adding another polymer. The goal 

of this study is to thoroughly analyse the synthesis of the PLA enhan cer: PGSMA (Poly(Glycerol Succinate-Co-Maleate) [1] 

so that in further research the accent can be set on actually adding it to PLA and no difficulties/hurdles will be found at 

the synthesis. PGSMA is a polyester made out of glycerol, succinic acid and maleic anhydride where the double bond of 

maleic anhydride makes it addable to PLA through reactive extrusion [2]. The synthesis will be done under N 2 and 

mechanical stirring at different temperatures, replacements for maleic anhydride will also be tested (see Figure 1). 

Heating the mixture at 180°C will create a three dimensional product and heating at 150 °C will create a linear product. 

The maleic anhydride replacements are: fumaric acid and itaconic acid (better for environment). During the synthesis 

samples will be taken and analysed with FTIR, DSC & GPC to determine the progress and speed of the reaction. At 180 °C 

this is to determine the gel point so that the synthesis will not go beyond that (the product becomes unusable). 

Keywords: PLA enhancer, PGSMA, Reactive extrusion, gel point. 


Figure 1: Overview study. 

[1] Valerio, Oscar, et al. “Sustainable Biobased Blends of Poly(Lactic Acid) (PLA) and Poly(Glycerol Succinate-Co-Maleate) 

(PGSMA) with Balanced Performance Prepared by Dynamic Vulcanization.” RSC Advances, vol. 7, no. 61, 2017, pp. 38594 – 

38603., doi:10.1039/c7ra06612k. 

[2] Valerio, Oscar, et al. “Synthesis of Glycerol-Based Biopolyesters as Toughness Enhancers for Polylactic Acid Bioplastic 

through Reactive Extrusion.” ACS Omega, vol. 1, no. 6, 2016, pp. 1284–1295., doi:10.1021/acsomega.6b00325. 

33


Biobased Polyesters From Ferulic Acid Derivatives 

Author 

Robin van den Kieboom 



Dennis Molendijk, Jack van Schijndel 

esters From Ferulic Acid Derivatives 

Abstract 

The polymer industry is one of the most important chemical industries in the world. Many of the polymers used 

worldwide are based from oil. 4% of the global oil- and gas production is used to produce polymers [1]. With the oil 

reserves slowly running dry, the demand for biobased polymers is quickly rising. Polyesters synthesized from ferulic acid 

could be a possible replacement for the oil-based PET (polyethylene terephthalate). Ferulic acid is a hydroxycinnamic acid 

derivative that can be produced from vanillin, a naturally occurring hydroxybenzaldehyde. The aim of this project produce 

at least dimers from ferulic acid, using a melt-polycondensation reaction. Secondly, to hydrolyse the polymer back to 

monomer, and finally, to re-polymerize the monomer to prove that the polymer can be recycled. FTIR, HPLC, DSC and 

HNMR were used to analyse both the polymer and monomer. A yield of at leas t 70% was expected within 3 hours. The 

project started with a screening (1/5 of full-scale) to find de fastest catalyst for the polycondensation. The catalysts were 

chosen for their use in standard esterfications, and cons isted of various Lewis acids [2] and Bronsted acids. This catalyst 

was used in the full-scale polymerisation. 5 mol% catalyst was used in both cases. The polycondensation was executed 

under vacuum at 110ºC. The reaction stops when the melting point of the polymer exceeds this temperature. After 

analysis the polymer was hydrolysed using 1M NaOH solution, and purified with L/L extraction to retrieve the monomer. 

Keywords: Polyester, Ferulic Acid, Biobased Polymer, PET replacement, Polymerisation, Polycondensation, Melt - 

Polycondensation, Hydrolysis. 

Table of contents 

Figure 11: Full reaction equation. 

[1] L. Mialon, A. G. Pemba en S. A. Miller, „Biorenewable Polyethylene Terephtalate Minics Derived From Lignin and Acetic Acid,” 

Green Chemistry, vol. 12, nr. 10, pp. 1677-1872, 2010. 

[2] A. M. B. Santos, M. Martinez en J. A. Mira, „Comparison Study of Lewis Acid Type Catalysts on the Esterification of Octanoic Acid 

and n-Octyl Alcohol,” Chem. Eng, Technol., vol. 19, nr. 1, pp. 538 -542 , 1996. 

34


Synthesis of a biobased and biodegradable “Super Absortbent Polymer” 

Author 

Fabian van Acker 

iobased and biodegradable “Super Absortbent Polymer” 



Betty Oostenbrink 

Abstract 

The research that has been done is on the article "Synthesis of superabsorbent polymer using citric acid as a biobased 

monomer" from H. Kim [1] In this article, from a citric acid that serves as a monomer, a super absorbent polymer is 

synthesized by means of a matching diol that serves as a "counterpart".The aim of this research is to realize the synthesis 

of a biobased and biodegradable "Super Absorbent Polymer" (SAP) from Citric acid with Glycerol instead of butanediol 

that is used in the previous research in order to obtain a polymer that is an absorbent rate of 2 200% or higher and 

biodegradable[2]. 

The expectation is that the reaction will be able to be shortened by insulating and increasing the temperature. In the 

previous research the synthesis is carried out at 155 degrees without insulation, which ensures that the water can be 

drained better. Figure 1 shows the reaction equation that from citric acid, monosodium citrate and glycerol synthesizes a 

superabsorbent polymer, then by means of HDI the polymer can be further crosslinked for an increasing absorbing effect, 

which can be seen in figure 2. 

Keywords: Esterfication, Super absorbent polymer, Biopolymer. 


Figure 1: Reaction equation. 

Figure 2: Super absorbent polymer. 

[1] Kim, H. J.; Koo, J. M.; Kim, S. H.; Hwang, S. Y.; Im, S. S. Polym. Degrad. Stab. 2017, 144, 128–136. 

[2] Ruttscheid, A.; Borchard, W. Eur. Polym. J. 2005, 41 (8), 1927–1933. 

35

36

Group index 

SPOC4 

The kinetics of the Knoevenagel condensation with amino 

acid-based catalytic intermediaries. 

Wolf Elenbaas 

Reconstructing the Knoevenagel condensation 

Quassim L’Karkouri 

Isolation of catalytic intermediates and acetylated analogs 

from amines and aromatic aldehydes Green Knoevenagel 

Condensation 

Alexandros Politis 

Synthesis of bisoxazolines out of PET an PLA waste 

Meike Voeten 

Chemical recycling to Oxazolines 

Ian Bouwmeester 

37

38

The kinetics of the Knoevenagel condensation with amino 

acid-based catalytic intermediaries. 

Author 

Wolf Elenbaas 




Abstract 

One of the most useful bonds to form in organic chemistry are carbon -carbon bonds, yet these bonds are very difficult to 

form. Even though it is possible with alkyl halides and/or with heave metal-ligand complexes, these reactions are very 

environment unfriendly [1]. The Knoevenagel or aldol condensation is an alternative way to form these bonds. Durin g 

these reactions a carbon-carbon bond is formed between an aldehyde and a ketone. The difference between these 

reactions are the catalysts that is used. The aldol condensation uses acids or bases to catalyse the reaction and during the 

Knoevenagel condensation amines are used. Knoevenagel has discovered that using amines greatly increases this reaction 

rate, even if a very small amount of amine is added [2]. 

In this project the catalytic intermediaries are synthesised with an amine with benzaldehyde, whic h forms a Schiff base or 

aminal, depending on what order of amine is used. In Figure 1 are the structures shown of some of the catalytic 

intermediaries. Once these intermediaries have been isolated and purified, they are used in the Knoevenagel 

condensation. In Figure 2 is the Knoevenagel condensation shown with benzaldehyde and dibenzyl -malonate. The yield 

was determined on the HPLC and the reaction rates were calculated. 

Keywords: Organic catalysts, Reaction kinetics. 


Figure 1: Structures of the catalytic intermediaries after 

benzaldehyde has reacted with different orders of amines. 

Figure 2: Reaction equation of the 

Knoevenagel condensation. 

[1] Wade L. G., Simek J.W., Organic chemistry. (2016) Reactions of Organometallic compounds: 514 -530. 

[2] Knoevenagel E., Ueber eine darstellungsweise der glutarsäure. Berichte der deutschen chemischen Gesellschaft. 

1894;27(2):2345-2346. 

39

Reconstructing the Knoevenagel condensation 

g the Knoevenagel condensation 

Author 

Ouassim L’Karkouri 




Abstract 

Green chemistry is becoming an important factor with chemical processes. The Knoevenagel condensation is a variant of 

the aldol condensation, the aldol condelsation is one of the oldest chemical reaction to form a carbon -carbon bond. The 

aldol condensation can either be base or acid catalysed. The Knoevenagel condensation is the same reaction as the aldol 

condensation but with amines as catalysis[1]. However in the present day the Knoevenagel condensation is documented 

in literature with the same mechanism as the aldol condensation[2]. We think that this is partially incorrect, the amines 

used in the Knoevenagel condensation act as organocatalyst instead as a base (figure 1). The goal of this research is to 

determine the catalytic intermediate and its catalytic activity of ammonium, 2 -aminoethanol and piperidine in the 

Knoevenagel condensation of benzaldehyde, 4-nitrobenzaldehyde and 4-methoxybenzaldehyde with diethylmalonate. We 

hypothesise that the catalytic intermediate of ammonium and 2 -aminoethanol a schiff’s base is and piperidine a bis 

aminal is. The Schiff’s base intermediates were created by letting benzaldehyde react with ammonium and 2- 

aminoethanol at 40°C which results in a condensation. the bis aminal intermediate was created by letting benzaldehyde 

react with piperidine at normal conditions. These intermediates are analysed with FT-IR, 1 H-NMR and mel The catalytic 

activity of these intermediates is determined by letting benzaldehyde react with diethylmalonate with 2,5% m/m % 

catalytic intermediate at 80°C and 100°C. the yield is monitored per time unit with RP-HPLC. 

Keywords: Aldol condensation, Knoevenagel condensation, catalys t, Schiff’s base, Bis-aminal 


Figure 1: proposed knoevenagel condensation path with ammonium. 

[1] E. Knoevenagel, '"Condensation von Malonsäure mit aromatischen Aldehyden durch Ammoniak und Amine," Berichte 

der deutschen chemischen Gesellschaft, vol. 31, no. 3, pp. 2596 -2619. 

[2] A.C.O. Hann and A. Lapworth, '"VII.-Optically active esters of small beta]-ketonic and small beta]- aldehydic acids. Part 

IV. Condensation of aldehydes with menthyl acetoacetate," J.Chem.Soc., Trans., vol. 85, no. 0, pp. 46-56. 

40

Isolation of catalytic intermediates and acetylated analogs from 

amines and aromatic aldehydes Green Knoevenagel Condensation 

Author 

Alexandros Politis 

ATGM Academie voor Technologie Gezondheid en Milieu 


Avans Hogeschool, Jack van Schijndel 


Abstract 

The formation of carbon-carbon bonds is always sought after in organic chemistry. In The Knoevenagel Condensation 

carbon-carbon bonds are created with the use of large amounts of basic solvents such as pyridine. [1] The difficult part in 

this is creating them in a greener way then is currently being done. The Green Knoevenagel Condensation introduces the 

use of a catalytic amount of organocatalyst and no solvent. It creates a catalytic intermediate (Schiff -base) which in turn 

catalyzes the reaction. The goal of this study is to synthesize catalytic intermediates, shown in Figure 1, and acetylated 

analogs from ammonia, benzylamine, piperidine together with benzaldehyde, 2 -hydroxy-benzaldehyde, 3-hydroxybenzaldehyde 

and 4-hydroxy-benzaldehyde. [2] Subsequently the catalytic activity of these catalytic intermediates will be 

determined relative to each other using a HPLC analysis. First, the hydroxy-benzaldehydes are acetylated using acetic 

anhydride and sodium acetate. This is being done to protect them from any reactions that may occur with the added 

amine. After this the benzaldehyde and the amine of choice are added together in their respective ratios. Mol sieves are 

being used to absorb water from the reaction, as water retains equilibrium and keeps the Schiff -base from being able to 

be isolated. After this reaction the Schiff-base is purified and analyzed. Last, (hydroxy)benzaldehyde and dibenzyl 

malonate are added 1:1 together with 5 mol% catalytic intermediate. The reaction is followed using TLC and conversion is 

determined on HPLC. 

Keywords: Knoevenagel Condensation, Organocatalyst, catalytic intermediate, Schiff-base 


Figure 1 Benzaldehyde and amines forming catalytic intermediates and reacting with dibenzyl malonate. 

[1] Rao, B. V. S. K, Vijayalakshmi P, Subbarao R. Synthesis of long-chain €-3-alkenoic acids by the Knoevenagel 

condensation of aliphatic aldehydes with malonic acid. Journal of the American Oil Chemist’ Society. 1933;70(3):297-299. 

doi: 10.1007/BF02545311 

[2] G. Jones. Organic reactions the Knoevenagel condensation. 

41

Synthesis of bisoxazolines out of PET an PLA waste 

Author 

Meike Voeten 




Abstract 

Polyethylene Terephthalate more known as PET is one of the most used polymers in th e food- and drink packaging 

industry because of the excellent physical and chemical properties. Due to its non -biodegradability, PET waste is an 

serious environmental problem. The most viable option of reducing the problem is the recycling of PET waste. It can take 

place in two different forms: mechanical and chemical recycling, this study is focused on chemical recycling. Another 

solution is using compostable materials such as Polylaticacid (PLA) instead of PET[1]. The goal of this study is to chemicall y 

recycle PET waste to 1,4-bis(5,6-dihydro-4H-1,3-oxazin-2-yl) PBOx6 and isolate 3-hydroxypropylterephtalamide BHPTA as 

intermediate shown in figure 1, also the possibilities of chemical recycling PLA are being studied. The chemical reaction of 

BHPTA out of PET waste was created by aminolysis[2]. Zinc acetate was used as a catalyst in this reaction. While heating 

the solution 3-aminopropanol was substituted on both sides of PET. After analyses of BHPTA by melting point, FT-IR and 

HPLC the second step in the recycling process can be practised. Using thionylchloride and oxalylchloride as catalyst, 

BHPTA enters the ring closure to PBOx6. This method was also used by PLA recycling. PBOx6 can be used as torque 

molecule or as chain extender which can reacted with the carboxyl acid in the recycling of PET. Besides that the 

bisoxazoline can deployed by other condensation polymerisations. 

Keywords: PET-recycling, Aminolysis, Ring closure, Bisoxazoline. 


Figure 1. Chemical recycling of PET by aminolysis and ring closure. 

[1] Bartolome, L., Imran, M., Cho, B. G., & Al-Masry, W. A. (2012). Recent developments in the chemical recycling of PET. 

Material recyling-trends and perspectives, 65-72. 

[2] Shah, R. V., Borude, V.S., & Shukla, S. R. (2013). Recycling of PET waste using 3-amino-1-propanol by conventional or 

microwave irradiation and synthesis of bis-oxazin there form. Journal of Applied Polymer Science, 127(1), 323-328. 

42

Chemical recycling to Oxazolines 

Author 

Ian Bouwmeester 



Jack van schijndel 

Abstract 

Many soft drinks are drunk from Polyethylene Terephthalate (PET) bottles. PET is made with terephthalic acid and 

ethyleen. This substance is extracted from petroleum oil and petroleum is very polluting, so It is necessary to recycle PET 

so that this bottle production can continue without pollution. [1] 

To be able to produce a 100% recycled PET bottle we need to look at chemical recycling because it does not affect the 

chain length of the polymer. In this study PET is converted by aminolysis to bis (2 -hydroxyethylene) terephthalamide 

(BHETA) where BHETA can be converted to 1,4-bis (4,5-dihydro-3H-1,3-oxazin-2-yl) benzene (PBOx5). In addition to the 

use of PET, this study looks into whether an oxazoline can be made from PLA (PolyLacticAcid). [2] [3] 

to make PBOx5 first step is to make BHETA from PET in the reaction ethanolamine and catalyst is used. In this sub -study it 

is investigated whether a catalyst has a positive influence on the yield of BHETA. In addition, it is examined with which 

method the highest yield can be achieved. A microwave reflux synthesis varied between 5 to 8 minutes is compared with 

a 5 hours reflux. In the reaction of BHETA to PBOx5 two catalysts are compared thionyl chloride and oxalyl chloride in 18 

hour stir reaction. PLA reaction is done with the same method as PET 

The maximum yield is expected to be the microwave synthesis of 7 minutes in addition, thionyl chloride is expected to 

generate the highest yield of PBOx5. It is also expected that it is possible to make PLA an oxazoline. 

Keywords: Oxazoline, PET, PLA 


Figure 12:Reaction of PET to PBOx5. 

[1] N. Pingale en S. Shukla, „Microwave-assisted aminolytic depolymerization of PET waste,” European Polymer Journal, p. 

2695–2700, 2009. 

[2] G. M. M. S. Sadeghi en M. Sayaf, „From PET Waste to Novel Polyurethanes,” Material Recycling – Trends and 

Perspectives, pp. 357-363, 2012. 

[3] R. V. Shah, V. S. Borude en S. R. Shukla, „Recycling of PET Waste Using 3 -Amino-1-propanol by Conventional or,” 

natural of applied polymer science, 2012. 

43

44

Group index 

SPOC5 

Molecular Imprinted Polymer om 10-DAB te isoleren uit 

Taxus extract 

Sem van der Pijl 

10-DAB 

Ismael Nouhi 

MIP synthesis of 4-vinylpyridine 

Ilse van Kessel 

The synthesis of block copolymers based on styrene 

analogues using a (Macro)-RAFT emulsion polymerization. 

Neline van Loon 

Biobased Block-Copolymers due ATRP 

Sanne van Eijnde 

RAFT polymerization of a biobased block-copolymer 

Rico Cavalcante 

45

46

Taxus extract 

Molecular Imprinted Polymer om 10-DAB te isoleren uit 

Taxus extract 

Author 

Sem van der Pijl 

Academy of Technologie, Gezondheid en Milieu 


Lectoraat AVANS 

Frank Luijkx en Edward Knaven 

Abstract 

Het Lectoraat van AVANS doet onderzoek naar het component 10-deacetyl baccatin-lll (10-DAB). Deze stof is gemakkelijk 

te verkrijgen van het restafval van de plant Taxus Baccata L. De stof 10-DAB wordt toegepast als precursor om Paclitaxel 

te synthetiseren. Deze stof helpt tegen het bestrijden van kanker en is daarom erg in trek om deze toe te passen op de 

mens. De 10-DAB wordt in dit onderzoek geïsoleerd door een Molecular Imprinted Polymer (MIP) te polymeriseren 

m.b.v. emulsiepolymerisatie. De MIP bestaat uit het functionele monomeer 2 -Hydroxy-ethyl-methacrylate(HEMA), een 

crosslinker TRIM en heeft een template van 10-DAB die er voor zorgt dat de 10-DAB in een extract onttrokken wordt van 

de andere componenten die aanwezig zijn. Het doel van het onderzoek is om 10 -DAB te isoleren uit het extract van de 

Taxus Baccata L. m.b.v. de MIP die verkregen is met het uitvoeren van emulsiepolymerisatie. De verwachting is dat de 

selectiviteit en de absorptie van de MIP met HEMA als monomeer boven de 80% zal waargenomen worden. De 

emulsiepolymerisatie is uitgevoerd bij 80°C en duurt 16uur om uit te voeren. Hierbij worden conversies gemeten tijdens 

de polymerisatie. Aflopend van de emulsiepolymerisatie wordt het polymeer opgewerkt en geanalyseerd met DSC, TGA 

en GPC. Verder wordt de absorptie en selectiviteit berekend van de MIP. 

Keywords: MIP, 10-DAB, Template, Emulsiepolymerisatie 


Figure 13: Poly HEMA. 

Figure 14: Reactie HEMA met Crosslinker TRIM. 

[1] Reza Panahi et al 

[2] Yonghua Xiao et al. 

[3] Mehran Javanbakhi et al. 

47

Synthesis of a core-shell Molecular Imprinted Polymer for 

the isolation of 10-deaccetylbaccatine lll out of Taxus 

10-DAB 

Author 

Ismael Nouhi 



Lectoraat Avans 

Sonny van Seters 

Abstract 

In this research, an attempt was made to make a core-shell molecularly-inprinted polymer (MIP) by means of emulsion 

polymerisation with the aim of isolating 10-deacetylbaccatine III (10-DAB) from raw Taxus Baccata L. extract. The core 

structure was prepared using methyl methacrylate (MMA) as a functional monomer and ethylene glycol dimethacrylate 

(EGDMA) as a crosslinking agent. The shell was made by emulsion polymerization with 10 -DAB as template molecule, 2- 

vinylpyridine (2-VP) as functional monomer and trimethylolpropane trimethacrylate (TRIM) and EGDMA as cro ss-linking 

agents. The synthesized MIP and NIP was characterized by thermogravimetric analysis (TGA), Fourier transform infrared 

spectroscopy (FTIR) and Differential scanning calorimetry (DSC). The MIPs and NIPs made were washed with methanol, 

the different fractions were measured with a UV spectrophotometer and high -pressure liquid chromatography (HPLC) for 

detection of 10-DAB and impurities in the fractions. A conversion of 89% was achieved for the core seed particles with a 

weight percentage of 71.1 mg / ml solid particles in polymer solution made. Initial conversions between 20% and 30% 

were achieved for making the MIP and NIP. Adjustment and optimization of the recipe resulted in a conversion of 59% 

within a reaction time of 2 hours. 

Keywords: Molecularly imprinted polymer, NIP, 10-DAB, Paclitaxel, core-shell. emulsion polymerisation. 


Figure 1: Schematic representation principle of the molecular imprinting technique. 

[1] E.-M. Mehdi, D. Behrad, A. I. Fatemeh en S. Elnaz, „Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles 

for targeting anticancer delivery: Characterization and cellular cytotoxicity,” Materials Science and Engineering: C, vol. 

2016, nr. 62, pp. 626-633, 2016. 

[2] T. Mroczek en K. Glowmiak, „Solid-phase extraction and simplified high-performance liquid chromatographic 

determination of 10-deacetylbaccatin lll and related taxoids in yew species,” Journaol of farmaceutical and biomedical 

analysis, vol. 2001, pp. 89-102, 2001. 

[3] Lie-Ping, . Lu, . Xue-Hong, . Jun-zhong, . Sheng, . Tao, . Zhe-You en . Jian-Hang, „Molecularly imprinted polymers for 

selective extraction of synephrine from Aurantii Fructus Immaturus,” Analytic and Bioanaltytic Chemistry, nr. 3, pp. 1237 - 

1346, 2011. 

48


Author 

Ilse van Kessel 



Avans Lectorate 


Abstract 


Taxol is a medicine used against different kinds of cancer. For the production of Taxol mostly used is 10 -DAB (10- 

deacetylbaccatin III, this compound can be extracted from the Taxus Baccata L.. To simplify the extraction of 10 -DAB from 

the Taxus Baccata L. a MIP (Molecular Imprinted Polymer) can be used. A MIP is an highly selective polymer whereby the 

synthesis of a MIP uses a template of the molecule, a monomer and a cross linker. [1] The result is a high cross-linked 

polymer because of the new bonds between the template and the cross -linked polymer during the curing process. The 

template is removed and the permanent pores stay in the polymer. The polymer is highly selective for the template 

molecule (10-DAB). In figure 1 is the schematic representation of the synthesis of the MIP shown.[2] The goal of this study 

is the synthesis of a MIP with another functional monomer than used in earlier investigations. This MIP has to be specific 

for 10-DAB, the analysis that are used are HPLC, DSC, TGA and FTIR. 4 -VP (4-vinylpyridine) is used as functional monomer. 

The expectation of this study is that a MIP with 4-VP can be synthesised. The MIP will also be selective for 10-DAB and has 

a recovery higher than 80%. 

Keywords: Taxol, 10-DAB, MIP 


Figure 1: Schematic representation of MIP synthesis. 

[1] M. J. M. E.-M. R. D. &. F. A. Fatemeh Azizi Ishkuh, „Synthesis and characterization of paclitaxel-imprinted nanoparticles 

for recognition and controlled release of an anticancer drug,” Journal of materials science, vol. 48, nr. 68, pp. 6343-6352, 

2014. 

[2] B. v. d. Velde, „Synthesis of molecularly imprinted polymers (MIPs) of 10-DAB III particles using a magnetite core-shell 

approach,” Breda, 2017. 

49


analogues using a (Macro)-RAFT emulsion polymerization 

Author 

Neline van Loon 



Lectoraat Biobased Products 



analogues using a (Macro)-RAFT emulsion polymerization. 

Abstract 

The lectorate Biobased products is interested in replacing oil based monomers such as styrene in styrene analogues (4 - 

atoxystyrene, acetoxyl guaicol and acetoxy canolol) to make biobased polymers. The aim of this project is to make a block 

copolymer of styrene(analogues) and butyl acrylate in emulsion polymerisation using a Macro -RAFT agent. The problem 

with usual RAFT-agents is that there not soluble in water. There are three solutions for this problem (Figure 1). The first 

one is to use an emulsifying RAFT agent. The second solution is to use a Macro-RAFT agent. And the final solution is to 

force the RAFT agent in the loci by ultra-sonication (mini-emulsion). DSC and GPC are used to determine if a block 

copolymer is formed. Furthermore, conversion determination and kinetic studies are done to determine if there are RAFT 

conditions. It is expected that it is possible to replace styrene with styrene analogues and that it is possible to make a 

block copolymer by means of emulsion polymerization with an emulsifying RAFT agent or Macro-RAFT agent. The results 

up til now show that using 1 wt % RAFT-agent is not enough to gain RAFT conditions. 

Keywords: block copolymers, (Macro)-RAFT agent, emulsion polymerisation, styrene analogues. 


Figure 1: 1 = Emulsion polymerisation with emulsifying RAFT agent. 2 = Emulsion polymerisation with Macro-RAFT agent. 3 

= Min-emulsion polymerisation. 

[1]: S.Compiet, Vergelijking tussen emulsie, mini-emulsie en RAFT mini-emulsie polymerisatie, Breda: Avans Hogeschool, 

2017. 

50


Author 

Sanne van den Eijnde 




Abstract 


Nowadays a lot of plastics are being used in daily life. Because block co -polymers[1] can have many different properties 

and applications a lot of research is being done at the moment. The polymers are commonly synthesized from monomers 

based on oil. In order to make polymers more environmentally friendly, in this study these block-co-polymers will be 

synthesized from biobased monomers that have been synthesized by the biobased lab. 

The aim of this research is to synthesize block co-polymers by using biobased monomers, which will mainly be styrene 

analogues. This will be done by means of the ATRP[2 ] polymerization technique with Ethyl α-bromoisobutyrate as 

initiator. 

Block-co-polymers are expected to be synthesized without random polymers between the two different blocks. A yield of 

around 65% is expected with conversions of 70%. It is also expected that a first order kinetics has taken place in the ATRP 

mechanism. 

First, a poly 4-acetoxyxtyrene[3] block was synthesized with Ethyl α-bromoisobutyrate as initiator, CuBr as catalyst and 

the ligand PMDETA was added. All this was done in the MEK as a solvent. Subsequently, the first block of 4- 

acetoxythyrene-Br was worked up and dissolved again in MEK, after which the block of butyl acrylate was coupled in the 

same way only 4-acetoxythyrene-Br acted as a macro-initiator. 

Keywords: Block co-polymers, ATRP, 4-acetoxystyrene 


Figure 1: Reactie 4-acetoxystyreen naar poly 4-acetoxystyreen [ 1]. 

[1] T. Zoontjens, „Atom transfer radical polymerization,” Breda, 2017. 

[2] T. K. X.-y. L. M.-q. C. Man HUA1 en y, „Successful ATRP Syntheses of Amphiphilic Block Copolymers Poly (styrene-block- 

N,N-dimethylacrylamide) and Their Self-assembly,” School of Chemical and Material Engineering, Southern Yangtze 

University, Osaka, Japan, 2005. 

[3] H. Bergenudd, „UNDERSTANDING THE MECHANISMS BEHIND ATOM TRANSFER RADICAL POLYMERIZATION – 

EXPLORING THE LIMIT OF CONTROL,” Elsevier, Amerika, 2011 . 

51


Author 

Rico Cavalcante 




Abstract 


A common topic in the polymer chemisrty is the use of sustainable processes, like the synthesis of biodegradable plastics. 

Therefore a lot of research is done into the use of biobased monomers and polymers. For this reason, the goal of this 

research is the synthesis of block-copolymers from butylacrylate and the biobased styreneanalog 4-acetoxystyrene. For 

the synthesis of a block-copolymer, a living polymerization is required so that the polymer chains are able to polymerize 

with a second sequence afterwards. The RAFT polymerization is chosen as polymerization technique for its versatility. This 

polymerization is performed in presence of a RAFT agent, which undergoes a chain transfer mechanism so that the chains 

gradually grow and stay active, see figure 1 [1]. The hypothesis of this research is that the M n, molecular weight, vs 

conversion plot will have a linear relationship, as shown in figure 2. This linear relationship indicates the gradual growth of 

the polymer chains. Furthermore, a polydispersity index, PDI, between 1,0 and 1,5 is expected, which would mean tha t 

most of the chains are about the same length. The synthesis of the block-copolymer is performed in two steps. The first 

step is the polymerization of 4-acetoxystyrene. Then the second sequence of butylacrylate is polymerized onto this 

polymer. The RAFT agent used in this research is CPDTC. This RAFT agent works well with 4 -acetoxystyrene and acrylates. 

The polymerizations will be performed with a temperature of 75°C. This temperature results in the fastest polymerization 

with the highest conversion. The ratio between the RAFT agent and initiator was 3:1. A higher ratio would result in a 

higher molecular weight but a lower conversion [2]. A gravimetric analysis is carried out to control the polymerizations 

and the (block-co)polymers are analyzed with GPC and DSC. 

Keywords: Biobased styreneanalog, RAFT polymerization, Chain transfer mechanism 


Pm• S S 

S S S S 

+ 

Pn Pm C Pn Pm + Pn• 

Z 

Z 

Z 

Monomer 

Figure 1: Chain transfer mechanism of the RAFT agent. 

Monomer 

Figure 2: M n vs conversion graph for RAFT polymerization. 

[1] Matyjaszewski Polymer Group, „Features of Controlled/"Living" Radical Polymerizations,” Carnegie Mellon University, 

[Online]. Available: https://www.cmu.edu /maty/crp/f eatures.html. [Geopend 7 Maart 2018]. 

[2] W. C. Baer, „RAFT POLYMERIZATION OF POLY(BUTYL ACRYLATE) HOMOPOLYMERS AND BLOCK COPOLYMERS: 

KINETICS AND PRESSURE-SENSITIVE ADHESIVE CHARACTERIZATION,” Department of Chemistry and Biochemistry, 

University of North Carolina Wilmington, 2011. 

52

53

54

Group index 

SPOC6 

Synthesis of Beta-lactam in three steps 

Narjiss Ajary 

A three step synthesis to a β-lactam antibiotic drug 

Floran Hüpscher 

Isoxazoline ring opening by TBAT to form a β-lactam ring 

Linsey van Kempen 

Synthesis of Ligand for Nickle complex 

Frédérique Clifton 

Synthesis of a ligand for a synthetic [NiFe] hydrogenase 

model 

Egor Silin 

55

56

Synthesis of Beta-lactam in three steps 


Author 

Narjiss Ajary 



Paula Contreras Carballada 

Erik Rump 

eta-lactam in three steps 

Abstract 

Beta-lactam molecules are a part of antibiotic families and are commonly used for the treatment o f bacterial infections. 

The important part of the molecule is the four membered ring, which gives the molecule its reactive characteristics to 

break down cell walls of the bacteria. To prevent the bacteria from becoming resistant to the commonly used Beta-lactam 

antibiotics, like Penicillin, different Beta-lactam derivatives are synthesised [1]. In this study, the synthesis is executed in 

three steps. The first step being condensation reaction with N-benzylhydroxylamine and Ethyl glyoxylate, which gives a 

Nitrone. The Nitrone is then used for the second synthesis, which is a 1,3 Dipolar Cycloaddition, with trimethylsilyl 

acetylene. The formed isoxazole is then used for the third synthesis, which is shown in Figure 1. A fluoride source is used 

to remove the trimethylsilyl group, which then gives the Beta-lactam product [2]. The goal of this study is to find an 

effective fluoride source for the removal of the trimethylsilyl group in the third synthesis. In the original research of …, 

TBAF is used, but this contains water which can protonate the intermediate and this doesn’t form the desired product [3] 

That’s why sodium fluoride was used. The obtained products were purified with column chromatography and analysed 

with H-NMR and FT-IR. 

Keywords: Beta-lactam, 1,3 Dipolar cycloaddition, isoxazole, nitrone, fluoride 


Figure 1: Reaction of the synthesis of the Beta-Lactam molecule. 

[1] C. Hubschwerlen (2007). B-lactam Antibiotics. Comprehensive Medicinal Chemistry II. 480-488. 

[2] P. DeShong et al. (1994) A New Approach to the Synthesis of Monocyclic B -Lactam Derivatives. J. Org. Chem. 6282- 

6286. 

[3] P. Contreras Carballada,(2003). Untersuchung zur Darstellung von 5 -trimethylsilyl-substituierten Isoxazolinen und 

deren Spaltung zu B-lactamen. 

57

A three step synthesis to a β-lactam antibiotic drug 

Author 

ynthesis to a β-lactam antibiotic drug 

Floran Hüpscher 




Abstract 

In this study, the β-lactam antibiotic drug 2-Azetidinecarboxylic acid, 4-oxo-1-(phenylmethyl)-, ethyl ester (structure 

shown in the bottom right in figure 1) is synthesized using the commercially available chemicals ethyl glyoxylate, N - 

benzylhydroxylamine, trimethylsilylacetylene and cesium fluoride in a three step synthesis. In th e synthesis step, requiring 

a source of fluorine, TBAF (Tetra-n-butylammoniumfluoride) was used in literature but resulted in a low yield (a maximum 

of 31% was acquired)[1]. The low yield is possibly the result of the 5% water content in commercial TBAF so lutions[2] 

The aim of this study is to investigate the effect of using an anhydrous source of fluorine (cesium fluoride instead of TBAF) 

on the yield of the respective synthesis step. It is expected that the yield will be higher than 36%. The intermediate 

structure needed to synthesize the desired β-lactam product is synthesized using reflux apparatuses and is purified using 

column chromatography. This two-step synthesis of the intermediate is depicted in figure 1. The third and final step in the 

synthesis is a 96-hour reflux reaction using cesium fluoride as fluorine source. The reaction will be monitored using TLC 

and purified using column chromatography. The intermediates and the product are analyzed using FTIR and H -NMR 

spectroscopy. 

Keywords: β-lactam, trimethylsilyl group removal, cesium fluoride. 


Figure 1: The three step reaction path to synthesize β-lactam structure. 

[1] Chuljin. A. e. al., „A New Approach to the Synthesis of Monocyclic / beta-Lactam derivatives,” Journal of Organic 

Chemistry, vol. 59, nr. 21, pp. 6282-6286, 1994. 

[2] P. C. Carballada, „Untersuchung zur Darstellung von 5 -trimethylsilyl-substitulerten Isoxazolinen und deren Spaltung zu 

beta-Lactamen,” unpublished results, Berlin, 2003. 

58

Isoxazoline ring opening by TBAT to form a β-lactam ring 

Author 

Linsey van Kempen 




g opening by TBAT to form a β-lactam ring 

Abstract 

Because β-lactam antibiotics are a widely used medicine, bacteria will be resistent through the excessive exposure. 

Therefore, new molecules with improved activity have to be found. In this research a β-lactam will be synthesized in three 

steps (Figure 1). The focus lies within the last step. In the research of P. Contreras Carballada there was TBAF used in this 

step. However, this didn’t work [1] In this experiment TBAT (Figure 2) will be examined to open the isoxazoline ring of 5 

and form the β-lactam ring. A big advantage of TBAT in comparison with TBAT is that it is anhydrous [2]. The first step is 

the condensation of N-benzylhydroxylamine 1 with ethylglyoxylate 2 in MTBE to form 3. Isoxazoline 5 will be formed by a 

[3+2] cycloaddition of 3 with trimethylsilylacetylen e 4 in THF [3]. In the last step, TBAT 6 will react with 5 in THF to form β- 

lactam 7. The intermediates and the product will be analysed with 1 H-NMR and FT-IR. 

Keywords: antibiotics, TBAT, β-lactam, condensation, [3+2] cycloaddition 


Figure 1: Overal reaction scheme. 

Figure 2: Tetrabutylammonium difluorotriphenylsilicate (TBAT). 

[1] P. Contreras Carballada, Untersuchung zur darstellung von 5 -trimethylsilyl-substituierten isoxazolinen und deren 

spaltung zu bèta-lactamen, 2003 

[2] P. DeShong and A. S. Pilcher, Utilization of tetrabutylammonium triphenyldifluorosilicate as a fluoride source for 

silicon-carbon bond cleavage, J. Org. Chem, 1996, 61, 6901 -6905 

[3] P. DeShong et al, J. Org. Chem. 1994, 59, 6282-6286 

59

Synthesis of Ligand for Nickle complex 


Author 

Frédérique Clifton 

igand for Nickle complex 



University of Leiden 

Abstract 

In nature there are enzymes that can catalyse a reaction to produce H 2 gas, hydrogenases. This reaction is interesting, 

because the gas is a potential energy source [1]. It has been possible to reproduce this process with a metal catalyst, for 

example a Nickle complex [2]. This research is about synthesising a ligand for a stable complex, that gives the hydrogenase 

model. The goal is to synthesize this ligand in a 5 step synthesis with a 4 substituted benzene. 

Expected from this synthesis is that it will yield 67% of the product and that the University of Leiden will be able to make 

the Nickle complex [3]. The synthesis of the ligand is shown in Figure 1 below. The starting material was 1,2,4,5 - 

tetrakis(bromomethyl)benzene. First, the starting product has reacted in a Sn2 reaction with Thiourea. After the 

formation of the first product, hydrolysis executed with NaOH to create a thiol product. The third step was another 

substitution with 2-chloro-1-propanol. The following step was converting the OH group in to a Chloro atom using SOCl 2. 

This step resulted a shift of the two methyl groups. Last step is equal to the first step of the reaction, resulting the fina l 

product. After each reaction the product was analysed with FT-IR, H-NMR and TLC. 

Keywords: Hydrogenase, metal-ligand, Sn 2 -reaction. 


Figure 1: overall reaction. 

[1] S. Canaguier, V. Artero en M. Fontecave, „Modelling NiFe hydrogenase: nickel-based electrocatalysts for hydrogen 

production,” The Royal Society of Chemistry, pp. 315 -325, 2008. 

[2] ] J. Verhagen, M. Beretta, A. Spek en E. Bouwman, „New nickel complexes with an S4 coordination sphere; synthesis, 

characterization and reactivity towards nickel and iron compounds,” Elsivier, vol. Februari 2004, pp. 2687 -2693, 2004.J. 

[3] J. Verhagen, D. Ellis, M. Lutz, A. Spek en E. Bouwman, „Synthesis, characterisation and crystal structures of new nickel 

complexes in S4 coordination spheres; an unprecedented rearrangement during ligand synthesis,” Dalton, pp. 1275 -1280, 

2002 

60

Synthesis of a ligand for a synthetic [NiFe] hydrogenase model 

Figure 1 : Overall reaction 

Author 

Egor Silin 




ligand for a synthetic [NiFe] hydrogenase model 

Abstract 

Hydrogen gas is a good candidate to replace the fossil fuels as an energy carrier. The hydrogen economy relies on the 

vision to replace the fossil fuels, using hydrogen as a low-carbon energy source. A way of producing hydrogen gas is using 

a hydrogen evolution reaction with an electro catalyst. This is possible with an enzyme present in certain microorganisms 

and is called hydrogenase [1]. The goal of this study is to synthesize a ligand with all substituted carbons present in the 

benzene, which can be used for the synthesis of the hydrogenase model for the University of Leiden. The ligand must 

have a complex of four sulphur atoms, so it could donate electrons to the metal complex present in the hydrogenase 

model. This is shown in Figure 1. Currently the ligand is being synthesized using Hexakis(bromomethyl)benzene as starting 

material. First, the present bromides were replaced with thioureum groups and hydrolysed with a base, to create a 

thiolproduct. After the synthesis of the thiolproduct, the product has reacted with 1 -chloro-2-methyl-2-propanol, 

resulting a bridge where another sulphur atom can be attached. The next step was to replace the hydroxy group with a 

halogen, using the thionylchloride as reagent. This reaction gave a shift of the two present methyl -groups to the beta 

carbon[3]. At last, the product from the previous step has reacted with thioureum under nitrogen, resulting the final 

ligand product. This is shown in Figure 2. The monsters were analysed with FTIR and 1 H-NMR. 

Keywords: Hydrogenas e, metal-ligand, Sn 2 -reaction. 


Figure 1: Target molecule 

Figure 2: Reaction equation 

[1] Lubitz, W., Ogata, H., Rüdiger, O., & Reijerse, E. (2014). Hydrogenases. Chemical Reviews , 4081-4148. 

[2] ] Verhagen, J. A., Ellis, D. D., Lutz, M., Spek, A. L., & Bouwman, E. (2002). Synthesis, characterisation and crystal 

structures of new nickel complexes in S4 coordination spheres; an unprecedented rearrangement during ligand synthesis. 

The Royal Society of Chemistry , 1275-1280. 

61

62

Group index 

SPOC7 

Synthesis of a terpyridine ligand for tumor-targeting ruthenium 

complexes 

Ward van den Berg 

Synthesis of a terpyridine ligand used in photodynamic 

treatment 

Harmen Spakman 

Synthesis of a terpyrdine ligand for the application in 

photodynamic therapy 

Timo van Veen 

The synthesis of a terpyridine for the use of photo dynamic 

therapy 

Kevin van Eekelen 

Synthesis of peptides for IR folding studies in the gas phase 

Sanne Mol 


Ronnie Bosmans 

Peptide synthesis for unravelling protein misfolding in 

neurodegenerative diseases 

Femke van der Heijden 

63

64


Synthesis of a terpyridine ligand for tumor-targeting ruthenium complexes 

of a terpyridine Author ligand for tumor-targeting ruthenium complexes 

Ward van den Berg 



Radboud University 

Abstract 

Terpyridine is a ligand that can form a coordinating bond with a central metal atom and form a complex. Complexes of 

terpyrydine with ruthenium can be used for PhotoDynamic Therapy(PDT). PDT is a way of treatment for diseases like, skin 

cancer and Bowen’s disease [1]. It consists of 3 parts: a photosensitizer(PS), oxygen and laser light. The laser light excites 

the photosensitizer after which the excited electron falls back to its lower energy state and creates Reactive Oxygen 

Species(ROS) [2]. After the ROS cause enough damage to the cellular structure, it induces apoptosis and dies. The goal of 

this research is to synthesize the desired terpyridine ligand, tpy-MeCl and to analyze the intermediates and end product 

with 1 H-NMR, 13 C-NMR, MS and EA analyses. To reach this goal 2 synthetic routes were taken. Route 1 esterificates tpy- 

COOH with H 2SO 4 and MeOH to form tpy-COOMe which is then reduced with LiAlH 4 to tpy-MeOH. Route 2 directly 

reduces tpy-COOH with LiAlH 4 to form tpy-MeOH. However difficulties were described with the direct reduction of tpy- 

COOH by Willem Aarts [3]. The last step in both routes is the chlorination of tpy-MeOH to get tpy-MeCl. To follow the 

progress of the reaction it will be monitored with TLC. 

Keywords: Photodynamic therapy, Ruthenium complex, Terpyridine ligand, tpy-COOH, tpy-COOMe, tpy-MeOH, tpy-MeCl 


Figure 1: Reaction route for tpy-MeCl. 

[1] C. Robertson, D. Hawkins and H. Abrahamse, "Photodynamic therapy (PDT): A short review on cellular mechan isms 

and cancer research applications for PDT," Journal of Photochemistry and Photobiology B: Biology, pp. 2 -3, 2009. 

[2] R. Boyle en L. Josefson, „Photodynamic Therapy and the Development of Metal-Based Photosensitisers,” Metal-Based 

Drugs, p. 1, 2008. 

[3] W. Aarts, „Synthesis of a terpyridine ligand for ruthenium complexes; Application in photodynamic therapy of cancer,” 

2017 

65


Synthesis of a terpyridine ligand used in photodynamic treatment 

Author 

Harmen Spakman 




terpyridine ligand used in photodynamic treatment 

Abstract 

This project consists in the synthesis of a functional terpyridine derivate that could be part of active Ruthenium complex 

used in photodynamic treatment for it’s phototoxic activity used in tumor targeting. In which this Ruthenium complex in 

the form of [Ru(tpy)(bpy)Cl] 2+ will selectively destroy cancerous DNA. The synthesis path follows a reaction path consisting 

of a Claisen condensation of Acetone and Ethylpyridine-2-carboxylate in presence of sodium ethoxide as a base followed 

by a Krӧnke pyridine synthesis in which a ring closing reaction will occur in the presence of Ammonium acetate shown in 

figure 1. This path could show an alternative to conventionally used research paths which are widely used [1][2].Goal in 

this project will be to record a significant yield in the overall reaction over previous studies conducted at Avans 

Hogeschool. Products will be characterized by FTIR, NMR, TLC, Yield and the melting point will be determined. Further 

research could be conducted at Leiden University. 

Keywords: Synthesis, Claisencondesation, Krӧnke pyridine synthesis, Terpyridine, Terpyridine derivated, PDT 


Figure 1: Reaction scheme of followed reactions to complete the synthesis of the final terpyridine derivate. 

[1] M. C. Thompson, „The synthesis of 2,2':6',2"-terpyridine ligands - versatile,” Coordination Chemistry Reviews, School 

of Chemistry, University of Bristol, Cantock s Close, Bristol, BS8 1TS, UK, 1997 . 

[2] Synthesis and Adsorption Properties, Toward Some Heavy Metal Ions, of a New Polystyrene-Based Terpyridine 

Polymer Department of Chemistry, The University of Jordan, Amman 11942, Jordan2Laboratory of Applied Biochemistry, 

Department of Biology, Faculty of Sciences, University Ferhat Abbas, Setif 19000, Algeria 

66

Synthesis of a terpyridine ligand for the application in photodynamic therapy 

Author 

terpyrdine Timo van Veen ligand for the application in photodynamic therapy 




Abstract 

Worldwide is cancer one of the biggest causes of death [1]. A relatively new cure for cancer is called “Photo dynamic 

therapy”. In comparison with chemotherapy, photo dynamic therapy is an easier medication method for the patient. For 

this therapy a photo dynamic medicine is needed. The goal of this research is to synthesize this photo dynamic medicine, 

the ligand [2,2’:6,2”- terpyridine]-4’-ylmethanol. This ligand is shown in Figure 1. This ligand is able to form a complex with 

ruthenium. When a laser is applied on this complex it will become toxic for the tumour [2] . To synthesize this ligand a 4 

step synthesis is carried out. This reaction equation is shown in Figure 2. The first step is a reaction known as the furan 

pathway, with acetyl pyridine and furfural under basic conditions to form 4’-(Furan-2-yl)-2,2’:6’,2”-terpyridine. Step 2 is an 

oxidation with KMnO4 to synthesize [2,2':6',2''-terpyridine]-carboxylic acid. Next there will be a Fischer esterification to 

synthesize (Methyl)-2,2':6',2''-Terpyridine-4'-carboxylate. The final step is to reduce the ester product towards the goal 

molecule [2,2’:6,2”- terpyridine]-4’-ylmethanol by using NaBH4 [3] . All obtained products are purified by recrystallization 

and analysed by FTIR and 1 H-NMR. 

Keywords: Photo dynamic therapy, Terpyridine derivative, The furan pathway 


Figure 1: The goal molecule. 

Figure 2: Overall reaction equation 

[1] L. Torre, F. Bray, R. Siegel, J. Ferlay, J. Lortet-Tieulent en A. Jemal, „Global cancer statistics 2012,” Cancer Journal, nr. 

65, pp. 87-108, 2015. 

[2] V. Brabec en O. Nováková, „DNA binding mode of ruthenium complexes and relationship to tumor cell toxicity,” Drug 

Resistance Updates, nr. 9, pp. 111-122, 2006. 

[3] M. Heller en U. S. Schubert, „Functionalized 2,2′-Bipyridines and 2,2′:6′,2′′-Terpyridines via Stille-Type Cross-Coupling 

Procedures,” Journal of inorganic chemistry, pp. 8269 -8272, 2002. 

67


The synthesis of a terpyridine for the use of photo dynamic therapy 

Author 

Kevin van Eekelen 

of a terpyridine for the use of photo dynamic therapy 




Abstract 

Photo dynamic therapy (PDT) is a new way to treat cancer. In contrast to chemo - and radio therapy, PDT is a very targeted 

method to cure cancer. While chemo- and radio therapy also damage healthy cells in the body, the PDT only affects the 

cancer cells. To use PDT a photosensitizer is needed. This photosensitizer will be exposed to light of the right wavelength 

and undergo a reaction which will produce oxygen radicals. Those oxygen radicals will destroy the cancer cell [1]. In this 

research [2,2':6',2''-terpyridin]-4'-ylmethanol (Tpy-MeOH) will be synthesized, which can be used as a photosensitizer in a 

ruthenium complex. This molecule can be seen at the bottom left side of Figure 1. The goal of this research is to 

synthesize Tpy-MeOH in a 4-steps synthesis from 2-acetylpyridine, in which a minimum reaction yield is achieved of 50%. 

In these syntheses different reactions are done among which; aldol condensation, Michael addition, oxidat ion with 

KMnO 4, Fischer esterification and a reduction with NaBH 4. This can be shown in Figure 1 [2]. To purify the products after 

synthesis recrystallisation is applied. To characterize the synthesized products, the following techniques were applied; 1 H- 

NMR, 13 C-NMR, FTIR and MS. 

Keywords: photo dynamic therapy and terpyridine derivative synthesis. 


Figure 15: Synthesis route to Tpy-MeOH. 

[1] A. Y. Pawel Mroz, „Cell Death Pathways in Photodynamic Therapy o f Cancer,” cancers, vol. 3, pp. 2516-2539, 2011. 

[2] B. M. Katarzyna Czerwińska, „Copper(II) complexes of functionalized 2,2’:6’,2’’- terpyridines and 2,6-di(thiazol-2- 

yl)pyridine: structure, spectroscopy, cytotoxicity and catalytic activity,” Dalton Tran s., vol. 46, p. 9591–9604, 2017. 

68


Author 

Sanne Mol 

peptides Academy for of Technology IR folding for Health studies and Environment in the gas phase 



Abstract 

Alzheimer’s disease, Huntington disease and ALS are all amyloidosis diseases and are caused by the accumulation of 

misfolded peptides. These proteins will precipitate and an aggregate will be formed. A research at Radboud University 

Nijmegen studies the misfolding of peptides. Therefore, they need three tripeptides. These peptides are l -lysyl-lphenylalanyl-l-aspartic 

acid (KFD), l-lysyl-l-phenylalanyl-l-glycine (KFG) and l-α-aspartyl-l-phenylalanyl-l-asparagine (DNF). 

These will respectively form a big aggregate to no aggregate. The target molecules are shown in Figure 1 [1]. The goal of 

this study is to synthesize l-lysyl-l-phenylalanyl-l-glycine with a purity of 95%. The starting materials are the amino acids 

Boc-l-phenylalanyl-OH and H-l-glycine-OMe. The amino acids have a protecting group to prevent polymerisation. The first 

coupling will take place under the influence of HATU. The next step is to deprotect the amine of Boc -l-phenylalanyl-OH. 

This will occur under the influence of HCl. After that Boc-l-lysyl(Boc)-OH will react with H-l-phenylalanyl-l-glycine-OMe to 

Boc-l-lysyl(Boc)-l-phenylalanyl-l-glycine-OMe. Thereafter another deprotection of the Boc-group will take place and after 

that a deprotection of the OMe-group with LiOH [2]. The target molecule will be purified with RP-HPLC and analysed with 

FT-IR and 1 H-NMR. The analysis of the misfolding will be done at the Radboud University using a FELIX (Free-electron Laser 

for Infrared eXperiments). 

Keywords: Peptides, amyloidosis 


Figure 1. Target molecules, from left to right: KFD, KFG and DNF. 

[1] P. W. J. M. Frederix, G. G. Scott, Y. M. Abul-Haija, D. Kalafatovic, C. G. Pappas, N. Javid, N. T. Hunt, R. V. Ulijn en T. 

Tuttle, „Exploring the sequence space for (tri-)peptide self-assembly to design and discover new hydrogels,” 2014. 

[2] V. M. Krishnamurthy, V. Semetey, P. J. Bracher, N. Shen en G. M. Whitesides, Dependence of Effective Molarity on 

Linker Length for an Intramolecular Protein-Ligand System, Cambridge: Harvard University, 2006. 

69



Author 

Ronnie Bosmans 

eptides Academy for of IR Technology folding for Health studies and Environment in the gas phase 



Abstract 

Protein is an important class of biological macromolecules. They have a big variety of functions in the human body, like 

transport and communication, however the protein can misfold from an α-helix to a β-sheet, or the other way around and 

lose its function or gain toxicity, after which they will aggregate [1]. When these proteins aggregate they will cause 

different illnesses like Alzheimer, ALS and parkinsons [2]. To find out how these proteins misfold Radboud university 

needs three proteins, LysPheAsp(KFD), LysPheGly(KFG) and AspPheAsn(DFN) focusing on DFN. KFD forms aggregates the 

easiest where KFG forms them aswell but in a lower amount, and DFN will be the blanco as DFN doesn’t form aggr egates. 

Radboud university will follow the aggregation in relation with neurodegenerative diseases in the gas phase IR with the 

use of FELIX. The goal is to synthesise and purify the peptide, with a yield of at least 50 mg. HATU will be used as coupling 

reagent, with Boc protection group for the amine and a methyl esther protecting group for the carboxylic acid. The 

peptides were analysed using 1 H-NMR. FT-IR and LC-MS. 

Keywords: Protein, peptide synthesis, protheopthy 


Figure 16: Flowchart of the experiment A,C: coupling reaction, B,D: deprotection Boc and E deprotection OMe. 

[1] R. B. Carrell en B. Gooptu, „Conformational changes and disease - serpins, prions and Alzheimer's,” Elsevier, pp. 799- 

809, 1998. 

[2] J. W. Kelly, „Alternative conformations of amyloidogenic proteins govern their behavior,” Elsevier, pp. 11 -17, 1996. 

70

Peptide synthesis for unravelling protein misfolding in 

neurodegenerative diseases 

Author 

Femke van der Heijden 



of peptides for IR folding studies in the gas phase 

University of Nijmegen 

Abstract 

Alzheimer’s, Huntington’s, Parkinson’s disease and fifteen other well-known neurodegenerative diseases are caused by 

the misfolding and aggregation of proteins into abnormal and toxic species. The mechanism of t his process is shown in 

figure 1 [1]. Since the tracking of the conformational change of the proteins is still a challenge, no sufficient cure is yet 

been developed and thus more research needs to be done to cure millions of people from these protein mis folding 

disorders. At the University of Nijmegen, the folding of proteins is studied using gas -phase infrared spectroscopy to 

answer the question of why and how proteins form unwanted structures [2]. Three tripeptides are important structures 

for this research, due to the ease of forming an aggregate. One of these tripeptides is l-lysyl-l-phenylalanyl-laspartic acid 

(KFD), as shown in figure 2. KFD is the tripeptide which is most related to the so -called diseases, due to its high 

aggregation properties. In this research, KFD is synthesized using a 5-step synthesis, including microwave assisted 

coupling steps and traditional deprotecting steps. The coupling steps provide the attachment of the amino acids, while 

the deprotecting steps provide for the reappearing of the significant carboxyl and amino groups in the wanted structure, 

which where once protected to exclude side reactions [3]. After each coupling step the intermediary product is purified 

using recrystallization and after every individual step, the product is characterized using FT-IR and LC-MS analysis. 

Keywords: Proteopathy, Protein Misfolding, Alzheimer’s disease, IR Folding studies, Peptide synthesis. 


Figure 1: The Protein Misfolding and Aggregation Process . 

Figure 2: Tripeptide ‘’KFD’’. 

[1] E Herczenik en MFBG Gebbink, „Molecular and Cellular Aspects of Protein Misfolding and Disease,” The FSEB Journal, 

2008, pp. 2115-2133. 

[2] AM Rijs en J Oomens, Gas-Phase IR Spectroscopy and Structure of Biological Molecules, 2015, Switzerland : Springer 

International Publishing. 

[3] A Mahindra, KK Sharma en R Jain, „Rapid Microwave-Assisted Solution-Phase Peptide Synthesis,” Tetrahedron Letters, 

2012, nr. 53, pp. 6931-6935. 

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Dear reader, 

Acknowledgement 

s 

After a lot of planning, experiments, blood, sweat, tears and joys, the minor SPOC 2017-2018 

has come to an end after having to work until 22:00 p.m. under Sahara desert temperatures in 

sweaty lab coats and with half of the budget that would be necessary for the chemicals. 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, Betty Oostenbrink and Erik 

Rump for their great guidance, nudges in the rights 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, Mabel Kummeling, Marieke Tellekamp, Koen van Beurden, Dennis Molendijk, Laura 

van den Corput-Mensen, Marianne van Tilborg and Edward Knaven for their support during 

the implementation of the projects and help with difficulties in the lab. We would also like to 

thank the ‘conciërges’ for keeping the building open and not locking us up. A very special 

thank you to the delivery people from Domino’s, that brought us diner at the end of a very 

long working days. 

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

topics and their critical view on the results. 

Without these people SPOC 2017-2018 wouldn’t have been the same. 

With kind regards, 

The students of SPOC 2017-2018 

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