Catalytic Hydroformylation Reactions in Liquid-Liquid Multiphase Systems with Polymer Particles and Without Phase Transfer Agents

Catalytic Hydroformylation Reactions in Liquid-Liquid Multiphase Systems with Polymer Particles and without Phase Transfer Agents

vorgelegt von M.Sc. Bachir Bibouche ORCID: 0000-0002-9611-5325

von der Fakultät II - Mathematik und Naturwissenschaften der Technischen Universität Berlin zur Erlangung des akademischen Grades

Doktor der Naturwissenschaften Dr. rer. nat.

genehmigte Dissertation

Promotionsausschuss: Vorsitzender: Prof. Dr. Matthias Bickermann Gutachter: Prof. Dr. Dieter Vogt Gutachter: Prof. Dr. Reinhard Schomäcker Gutachter: Prof. Dr. Paul Kamer

Tag der wissenschaftlichen Aussprache: 26.07.2019

Berlin 2019 Zusammenfassung

Die Nutzung von molekularen Katalysatoren ermöglicht selektive und ressourcenschonende Reaktionen. Eine große Herausforderung dieser Katalysatoren ist jedoch die Wiederverwendbarkeit, da sie oft bei der Produktabtrennung inaktiv werden. Thema dieser Arbeit sind mehrphasige, flüssig-flüssig Systeme, in denen Reaktionen mit molekularen Katalysatoren durchgeführt werden, sowie deren Recyclingprozesse. In den verschiedenen Ansätzen ist immer eine wässrige Phase mit einem wasserlöslichen Katalysator vorhanden. Ziel ist, die gesamte wässrige Phase, inklusive Katalysator zu recyceln. Edukt und Produkt der Reaktion bilden eine unpolare Phase und können nach der Reaktion leicht abgetrennt werden.

Der Erste Teil der Arbeit behandelt Polymerpartikel, welche in mehrphasigen, katalytischen Systemen als Phasentransferstoffe dienen und so die Reaktion ermöglichen. Die Charakterisierung der Partikel zeigt, dass sie reproduzierbar hergestellt werden können, ca. 100 nm groß sind und die eingesetzten Katalysatoren an ihrer Oberfläche tragen können. In mehrphasigen Hydroformylierungsreaktionen von 1-Octen konnten mit ihrer Hilfe die Katalysator-typische Selektivität erreicht werden. Die Produktabtrennung in solchen Partikel- Systemen ist oft ein Problem, kann aber durch niedrige Rührerdrehzahlen verbessert werden. Außerdem konnte gezeigt werden, dass die sich bildenden Emulsionen entfernt werden können. Eine andere Option ist das Recycling der Emulsionsphase, da diese sich dabei nicht akkumuliert.

Ein anderes System, welches in dieser Arbeit behandelt wird, ist ein Mehrphasensystem ohne jegliche zugesetzte Phasentransfermittel. In diesem Fall ist die Selektivität etwas niedriger und bei Reduzierung des Druckes unter 80 bar sinkt die Selektivität, unter den verwendeten Bedingungen, stark. Das System ohne Polymerpartikel hat allerdings große Vorteile; das Recycling ist sehr einfach und effizient und die Reaktion ist erstaunlich schnell. Dass keine Partikel synthetisiert werden müssen, ist ein weiterer Vorteil.

Verschiedene flüssig-flüssig Mehrphasensysteme werden in der Arbeit besprochen und im letzten Kapitel wird ein Auswahlverfahren präsentiert. Dieses soll ermöglichen festzustellen, ob eine Reaktion in einem bestimmten Mehrphasensystem durchführbar ist.

I Abstract

Utilizing molecular catalysts allows for selective and resource efficient reactions. One big challenge of utilizing these catalysts is their recyclability, since they often get deactivated when separating the product. This work deals with different liquid-liquid, multiphasic, reaction systems with molecular catalysts, and their recycling. In the discussed approaches, there is always an aqueous phase, which contains the water-soluble catalyst. The goal is to recycle the entire aqueous phase, and with it the precious catalyst. Substrate and product form a separate nonpolar phase, which can, in theory, be easily separated after the reaction.

The first part of this work deals with the synthesis and characterization of polymer particles, which are used as phase transfer agents for the described multiphase systems. It is shown that the particles can be synthesized in a reproducible fashion, have a size of ca. 100 nm and act as catalyst carriers. The use of these particles in multiphasic hydroformylation reactions of 1-octene lead to the selectivity that is typical for the utilized catalyst. While product separation is a common issue in this system, it can be dealt with by using low stirring rates. In addition, the emulsions that are usually formed can be recycled together with the aqueous phase, as they do not accumulate when doing so.

Another system that is being dealt with in this work is the multiphasic reaction approach without any added phase transfer agents. In that case, the selectivity is a bit lower, than when using the polymer particles and it drops rapidly, when going below 80 bar. Not having any added phase transfer agents in the system has big advantages though; recycling is simple and efficient, and the reaction is surprisingly fast. In addition, the synthesis of polymer particles is not required.

In this thesis, different multiphasic, catalytic reaction systems are discussed, and in the final chapter, a way to find the fitting one is presented. The aim is to have a set of criteria, followed by a few simple key experiments, which allow judging the applicability of a certain multiphasic system for a given reaction.

II List of abbreviations a Year acac Acetyl acetone ACN Acetonitrile AFM Atomic force microscopy aq. Aqueous b Branched c Concentration C Catalyst °C Degree Celsius cm Centimetre cmc Critical micelle concentration C4E2 Diethylene glycol butyl ether CTAB Cetrimonium (cetyl-trimethyl-ammonium) bromide d Doublet dd Doublet of a doublet D Diameter Dh Hydrodynamic diameter DLS Dynamic light scattering δ Chemical shift DMSO-d6 Deuterated dimethyl sulfoxide DVB Divinylbenzene FID Flame ionization detector GC Gas chromatography h Hour 1H-NMR Proton nuclear magnetic resonance spectroscopy HPLC High performance liquid chromatography Hz Hertz ICP-MS Inductively coupled plasma mass spectrometry ICP-OES Inductively coupled plasma atomic emission spectroscopy IL Ionic liquid J Coupling constant kg Kilogram kV Kilovolt l Linear L Phosphine ligand m Meter m Multiplet (in 1H-NMR context) M Molar concentration in mol/l Me Methyl group III mmol Millimole mg Milligram MHz Megahertz min Minutes ml Milliliter mwc Molecular weight cut-off n Molar amount nm Nanometer OAc Acetoxy group OATS Organic aqueous tunable solvents p Pressure PE Pickering emulsion PEG Polyethylene glycol Ph Phenyl group PP Polymer particles p.p. Percent points ppm Parts per million, e.g. mg per kg PTA Phase transfer agent RCH/RP Ruhrchemie-Rhône-Poulenc process rpm Rotations per minute s Second s Singlet (in 1H-NMR context) S Selectivity Schem Chemoselectivity Sregio Regioselectivity scCO2 Super critical CO2 SDS Sodium dodecyl sulfate SEM Scanning electron microscopy SFT Surface tension SILP Supported ionic liquid phase system SS Styrene salt monomer; (p-vinylbenzyl)- trimethylammonium tetrafluoroborate SX Sulfoxantphos t Time T Temperature TEM Transmission electron microscopy THF Tetrahydrofuran TMS Thermomorphic multicomponent solvent systems TOF Turnover frequency TPP Triphenylphosphine TPPDS Triphenylphosphine-3,3′-disulfonic acid disodium salt TPPMS Triphenylphosphine-3-sulfonic acid sodium

IV salt TPPTS Triphenylphosphine-3,3′,3′′-trisulfonic acid trisodium salt V Volume VA-086 2,2'-azobis[2-methyl-N-(2- hydroxyethyl)propionamide] VB-PEG p-(Vinylbenzyl)poly(ethyleneglycol) W Watt wt. Weight Y Yield Yald Yield towards aldehydes X Conversion Xald Conversion towards aldehydes

V Content

Zusammenfassung ...... I

Abstract ...... II

List of abbreviations ...... III

Content ...... VI

1 Introduction ...... 1

2 Theoretical part ...... 4

2.1 Green chemistry and the E factor...... 4

2.2 Catalysis ...... 6

2.2.1 Multiphase catalysis ...... 6

2.2.2 The Ruhrchemie/Rhône-Poulenc process as an inspiration ...... 7

2.2.3 Catalysis with phase transfer agents ...... 8

2.2.4 Switchable, multiphasic catalysis approaches ...... 12

2.2.5 Catalysis in other multiphasic liquid/liquid systems ...... 15

2.2.6 Catalyst immobilization and colloids as catalyst carriers ...... 18

2.2.7 The best multiphasic approach for a catalytic reaction ...... 20

2.3 The hydroformylation reaction...... 21

3 Results and discussion ...... 25

3.1 Polymer particle synthesis, properties and characterization ...... 25

3.1.1 Role of the monomers ...... 25

3.1.2 Monomer conversion during the polymerization reaction ...... 28

3.1.3 Optimization of the polymerization reaction ...... 28

3.1.4 Synthesis of polymer particles with different compositions ...... 30 VI 3.1.5 Characterization of the polymer particles ...... 31

3.2 Hydroformylation reactions with polymer particles as phase transfer agents ...... 36

3.2.1 Multiphasic hydroformylation reactions with polymer particles with different compositions ...... 37

3.2.2 The challenge of the phase separation ...... 38

3.2.3 Reaction optimization ...... 40

3.2.4 Substrate scope investigations for hydroformylation reactions ...... 50

3.2.5 Phase separation strategies ...... 54

3.2.6 Catalyst recycling ...... 58

3.2.7 Suzuki-Miyaura reactions with polymer particles in a multiphasic liquid-liquid system 62

3.2.8 Role of the polymer particles in the multiphasic hydroformylation reactions ...... 66

3.3 Multiphasic, catalytic hydroformylation reactions without phase transfer agents ...... 67

3.3.1 Ligand influence ...... 68

3.3.2 Proposed mechanism of the multiphasic reaction without phase transfer agents. 69

3.3.3 Influence of pressure on particle-free multiphase reactions ...... 70

3.3.4 Influence of stirring rate on particle-free multiphase reactions ...... 72

3.3.5 Influence of preformation conditions and aqueous volume on selectivity and conversion ...... 74

3.4 Development for key experiments for multiphasic reaction systems ...... 77

3.4.1 Determining the feasibility of micellar and of polymer particle multiphase systems for different reactions ...... 77

3.4.2 Theoretical assessment of reaction compatibility ...... 79

3.4.3 Chosen reactions for investigation with key experiments ...... 80

3.4.4 Conditions chosen for the key experiments ...... 81

VII 3.4.5 Key experiments and the comparison with optimized reactions ...... 82

4 Summary and outlook ...... 85

5 Experimental part ...... 88

5.1 Chemicals ...... 88

5.2 Preparation of the monomers ...... 88

5.3 Polymer particle preparation ...... 89

5.4 Catalyst carrier experiments ...... 90

5.5 Catalytic reactions and related procedures ...... 91

5.5.1 1-Octene hydroformylation ...... 91

5.5.2 Hydroformylation of other 1-alkenes ...... 91

5.5.3 Recycling experiments with centrifugation ...... 91

5.5.4 Recycling experiments including the Pickering emulsion ...... 91

5.5.5 Recycling experiments with diethyl ether for phase separation ...... 92

5.5.6 Recycling experiments without polymer particles ...... 92

5.5.7 Multiphasic hydroformylation reaction with surfactants ...... 92

5.5.8 Suzuki-Miyaura and Mizoroki-Heck coupling reactions ...... 92

5.6 Instruments and characterization methods ...... 92

5.6.1 Surface tension (SFT) and critical micelle concentration (cmc) ...... 92

5.6.2 Dynamic light scattering (DLS) ...... 93

5.6.3 Visual microscopy with UV-active dyes ...... 93

5.6.4 Atomic force microscopy (AFM) ...... 93

5.6.5 Transmission electron microscopy (TEM) ...... 93

5.6.6 Scanning electron microscopy (SEM) ...... 94

5.6.7 Zeta potential ...... 94

VIII

5.6.8 Nuclear magnetic resonance (NMR) ...... 94

5.6.9 Gas chromatography (GC) ...... 94

5.6.10 Inductively coupled plasma optical emission spectrometry (ICP-OES)...... 94

5.6.11 Inductively coupled plasma mass spectrometry (ICP-MS) ...... 95

6 Literature...... 96

7 Appendix ...... 103

7.1 Publications ...... 103

7.2 Additional information ...... 104

7.3 Danksagung ...... 112

1 Introduction

Modern day chemistry has come a long way. Things that were considered impossible just decades ago have shown to be reachable goals. Many technologies, advanced materials and new powerful medicines could be developed. And yet, there is still a long way to go. Especially in fine chemistry, such as the synthesis of drugs, there is normally a large production of contaminated waste. A way of getting chemistry to be less hazardous, and reducing the production of waste, is the concept of green chemistry.[1,2] There are 12 principles of green chemistry, and one of them is “catalysis”, meaning the use of a catalyst to reduce the energy and resources needed to obtain a product. Nowadays, most industrial processes make use of catalysts.[3] There are two main types of catalysts, homogeneous and heterogeneous ones. By definition a catalyst can produce multiple molecules of product per molecule of catalyst or active center during a catalytic reaction. Homogeneous catalysis using molecular catalysts is especially desired for its high selectivity and mild reaction conditions. There is a very common problem with that however; homogeneous conditions make it very difficult to separate a catalyst from the product after the reaction. In fact, homogeneous catalysts are often destroyed during the product separation. In a lot of cases though, the catalyst could in theory be used for many more reaction cycles.

In this work, a multiphasic approach to catalytic reactions is being applied, using two liquid phases. One uses water as a solvent and contains the catalyst. The other one contains the substrate before the reaction and of course the product after the reaction. Like oil and water they are not miscible. The catalyst can be a proper, solubilized molecular catalyst that is highly selective. Under reaction conditions, intense stirring enables contact of catalyst and substrate, although that is only true for some substrates and can pose a challenge. After the reaction the product separates from the aqueous phase and enables a simple product separation. The entire aqueous phase, including the catalyst, can then be reused. This produces no solvent waste, and enables a very efficient catalyst recovery. A simplified version of the system is shown in Figure 1. This way of doing catalysis gives the benefit of homogeneous catalysis while avoiding the destruction of the catalyst after the reaction, by enabling simple product separation. 1

Figure 1. General concept of a multiphasic reaction system with a molecular catalyst

This kind of system, while having strong advantages, can be challenging however. The separation of the aqueous catalyst phase and the product-phase is achieved due to polarity. However, if the substrate is very non-polar, it will have no relevant solubility in the aqueous phase, leading to no observable reaction. To overcome this issue, phase transfer agents can be utilized. Those normally have polar and non-polar parts, and help reducing the limitations due to transport phenomena. Surfactants are classic examples for this. In this work, special phase transfer agents in the form of functionalized polymer particles have been utilized. These are similar to polymerized micelles, in that they have a non-polar core and a polar shell, making them water soluble. The particles also contain ionic groups, with which they can interact with catalysts. It was found in previous work that the so called hydroformylation reaction of long chain alkenes could be performed with great success, when using these particles as phase transfer agents. The particular reaction is highly interesting, as the hydroformylation of long chain alkenes is indeed done on an industrial scale, but with a high energy cost and low selectivity towards the desired product, generating a lot of waste. The development of an alternative multiphasic reaction system with high selectivity and simple product separation while being able to recycle the catalyst would be quite desirable.

When working with the particles, it was discovered that the reaction does indeed work with long chain alkenes, even when not using phase transfer agents, something that was found surprising. The requirements are high pressures though, and the selectivity was also lower. Still,

2 this approach seemed promising as it is a simple system that allows easy product separation and the synthesis of the particles is not required in that case.

Finally it has to be mentioned that there are different approaches to recycle a catalyst with a multiphasic system, and all have their advantages and disadvantages. For example, the particle system described in this work would not work, when having a product that binds to the particles. Using surfactants as phase transfer agents instead, does solve that particular problem, but not all reactions are achievable with those. Therefore, in the final chapter of this work, a methodology is developed to determine if a particular multiphasic reaction system is suitable for a given reaction. The goal is to have a manual of different test reactions that give information about which particular multiphasic reaction system can be applied for a given reaction. The goal of this thesis is to show and continue to develop novel processes to give the field of chemistry tools to get closer to the principles of green chemistry.

2 Theoretical part

Aim of this thesis is the investigation of multiphasic liquid-liquid systems for catalysis. The focus lies on hydroformylation reactions of long chain alkenes and the use of micelle-like polymer particles as phase transfer agents. Another system that was investigated is one without any phase transfer agents at high pressures. In the theoretical part, different multiphasic liquid- liquid systems are discussed. Additionally, a motivation for these systems is derived from a look at applied catalysis.

2.1 Green chemistry and the E factor

In the early 1980s some chemist’s attention was drawn to waste production. Especially in fine chemistry, there was little focus on avoiding waste. A famous example was the synthesis of a compound that used dangerous trinitrotoluene as a substrate and produced 40 kg of solid, hazardous waste per 1 kg of product. The plant was indeed later shut down because the cost of waste disposal approached that of the revenue.[2] To gain a standardized method of evaluating waste production, the E factor was introduced and defined as E = kg(waste)/kg(product). The process described above would therefore have an E factor of 40, which is very inefficient.[4] Different chemical processes were looked at, when the E factor was first defined in 1992, showing that there are massive differences depending on the field. The estimated values for different industrial processes are shown in Table 1.

Table 1. E factors in chemical industry[2] Industry segment Tonnes per year E factor Oil refining 106-108 < 0.1 Bulk chemicals 104-106 < 1-5 Fine chemicals 102-104 5 - 25 Pharmaceuticals 10-103 25 - >100

As can be seen, the waste production in oil refining is minimal, while the waste production in fine chemistry and especially pharmaceuticals is very high. There are ways to reduce the E factor though. Better synthesis routes are one way and especially catalysis can make that possible.

Another very important way of looking at chemistry to make it more sustainable and eco- friendly is the concept of green chemistry.[1] It was developed by Anastas and Warner in 1998 and has 12 principles. Those principles are:

1. Prevent waste 2. Atom economy 3. Less hazardous synthesis 4. Design benign chemicals 5. Benign solvents & auxiliaries 6. Design for energy efficiency 7. Use of renewable feedstocks 8. Reduce derivatives 9. Catalysis (vs. stoichiometric) 10. Design for degradation 11. Real time analysis for pollution prevention 12. Inherently benign chemistry for accident prevention

The approach of using green chemistry does not only lead to environmentally friendlier, and less hazardous processes, it can also lead to more economical processes. A big motivation for the use of catalysts is to save costs, but at the same time it checks with multiple principles from green chemistry. Not only the obvious point 9, use of catalysts, but it also makes processes more energy efficient and more selective, producing less side products (derivatives) and leads to higher atom efficiency. Solutions that are in agreement with green chemistry are not known for all processes, so the development of green strategies is very desirable. With the concept of green chemistry, a focus was also put on green solvents.[5] While avoiding solvents altogether is sometimes the best option, doing so is not always possible. Solvents can be necessary for a multitude of reasons. Apart from bringing substrates together by solubilizing them, it can also be important for heat transfer, or enabling catalysis which would otherwise be mass transfer limited. While water is one of the greenest solvents available, there are also other solvent systems for which an argument can be made to be green, like super critical CO2, or micellar

5 systems.[6] These solvent systems are usually not yet applied a lot in industry and are a motivation for the development of new liquid-liquid multiphase systems.

2.2 Catalysis

80 % of all industrial processes are catalyzed.[3] The main types of catalysis are homogeneous and heterogeneous catalysis. Biocatalysis with enzymes is sometimes listed as another type, and also multiphasic catalysis with molecular catalysts could be viewed as not fitting into the other categories. Homogeneous catalysis means that the catalyst is in the same phase as the substrate, typically they are all solubilized in a solvent. Heterogeneous catalysis means that the catalyst is in a different state than the substrate, typically a solid catalyst and gaseous or liquid substrates. Homogeneous catalysis is usually more selective and can be performed under milder conditions, while heterogeneous catalysis requires harsher conditions. There is one huge advantage of heterogeneous catalysis however, and that is the ease of separating the product from the catalyst.

2.2.1 Multiphase catalysis

Heterogeneous catalysis is dominating the industrial field with ca. 80 % of all catalytic processes being heterogeneous.[3] Considering the advantages of homogeneous catalysis like higher selectivity, atom efficiency and energy saving, it is understandable that heterogeneous catalysis does not seem desirable. It appears that only the difficult separation of the catalyst and product prevents homogeneous catalysis from being dominant. For this reason, multiphasic reactions with molecular catalysts have been, and are being developed.[7,8] These reactions can be set up in different ways. One example is the use of two liquid phases, where one contains the molecular catalyst and one contains the substrate and product, see Figure 1 (Introduction). Another option is the use of a catalyst phase that is miscible with the substrate/product during the reaction, and is switched to become immiscible after the reaction and therefore allows an easy product separation. These switches can be a change in physical parameters, like temperature or pressure or be chemical, for example by introducing CO2.

The work presented in this thesis has been part of the SFB/Transregio 63, a research collaboration funded by the German Research Foundation, DFG. Different multiphasic reaction systems have been investigated in this project, namely micellar and thermomorphic systems, as well as ones utilizing so-called Pickering emulsions and polymer particles as phase transfer agents. These different systems were applied to a few example reactions, e.g. the hydroformylation of long chain alkenes. This allowed comparing the different approaches for given reactions. These different approaches, which seek to combine the advantages of homogeneous and heterogeneous catalysis, are reviewed in the following of this chapter. And while some proposed solutions for the hydroformylation reaction specifically[9] as well as for multiphasic reactions in continuous processes[10] can be found, the field has still a lot of room for discoveries.

2.2.2 The Ruhrchemie/Rhône-Poulenc process as an inspiration

One liquid-liquid multiphasic reaction system that is being applied in industry is the Ruhrchemie/Rhône-Poulenc process (RCH/RP). It is applied for the hydroformylation of mainly propene, and uses a Rh-based catalyst with triphenylphosphine-3,3′,3′′-trisulfonic acid trisodium salt (TPPTS) as a ligand. The catalyst is a proper molecular catalyst, solubilized in the aqueous phase, as the TPPTS ligand is water soluble (see Figure 2). The non-polar phase contains the substrate and product. It is a continuous, large scale process.[11]

Figure 2. Triphenylphosphine- 3,3′,3′′-trisulfonic acid trisodium salt (TPPTS)

The process has a high selectivity towards the linear aldehydes of 96 %, and very low Rh leaching in the ppb range. It leads to a simple product separation and catalyst recycling and is used to produce 800 000 tons of aldehydes per year.[12] The RCH/RP process is an elegant,

7 successful process but is only applicable to substrates that are sufficiently soluble in water. This means that aldehydes of chain lengths higher than five are not accessible by this process. In industry, long chain aldehydes are commonly synthesized in a homogeneous system which then requires a separation process that is more difficult. For alkenes up to C8, Rh-phosphine catalysts are being applied. For higher chain lengths however, the distillation conditions required lead to catalyst decomposition. This makes the cheaper cobalt the catalyst of choice for those processes. Cobalt catalysts are less selective and require harsher conditions. This makes a process similar to the RCH/RP one desirable to be applicable also for long chain alkenes.[13] Different processes that seek an equally simple product separation and catalyst recycling have been developed and often been inspired by the RCH/RP approach.

2.2.3 Catalysis with phase transfer agents

Catalytic liquid-liquid systems with a molecular catalyst in one phase and the substrate in another are promising reaction setups. In a system like that, the product can easily be separated from the catalyst while still having the advantages of using a molecular catalyst. This does work well for substrates with sufficient solubility in the catalyst phase, but requires modification in some cases. This is where phase transfer agents (PTA) can be used. They often have a polar and a non-polar part and help carry the substrate or catalyst into the other phase. PTAs can also reduce the interface tension and thereby increase the mass transfer by increasing the interface area. Examples for PTAs are quaternary ammonium salts, activated carbon, cyclodextrins and surfactants.[9] It should be noted that sulfonated, water soluble ligands are often surface active and therefore could be viewed as phase transfer agents. The use of a multiphase system with a non-polar phase with substrate (S) and product (P) and a polar phase is shown in Figure 3.

Figure 3. Scheme of a multiphasic reaction with two liquid phases and a phase transfer agent (PTA) carrying the substrate to the catalyst (C) phase.

2.2.3.1 Catalysis with surfactants Surfactants are the most classic example for molecules that have a polar and a non-polar part, bringing about characteristic properties. Surfactants form micelles above a so called critical micelle concentration (cmc). After reaching the cmc, adding more surfactant to a solution does not significantly lower the surface area, and almost all additional surfactant molecules form micelles.[14] There are different kinds of surfactants. One way of characterizing them is to differentiate them into anionic, cationic, zwitterionic and neutral surfactants. Examples for some of those are given in Table 2.

Table 2. Three example surfactants Cetrimonium bromid Cationic surfactant (CTAB)

Sodiumdodecylsulfat Anionic surfactant (SDS)

Marlipal 24/70 Non-ionic surfactant

n = 9-11, m = 7, Marlipal, as an industrial surfactant, has an average degree of n and m

Surfactants have been applied as phase transfer agents for different kinds of multiphasic, catalytic reactions, like C-C-coupling reactions.[15,16] Another example is the hydroformylation of long chain alkenes in a process that is inspired by the RCH/RP process.[15,17,18] Especially interesting is a continuous process that was operated for almost a week in a miniplant, with a yield of 25 % at optimal conditions.[19] The yield is reasonably high considering the very non- polar substrate 1-dodecene. What is also impressive is the continuous separation in a decanter, allowing the continuous separation of emulsion systems. This is not a trivial task, as the phase behavior can be complex.[20]

2.2.3.2 Catalysis with cyclodextrins Cyclodextrins are cyclic oligosaccharides typically with 6, 7 or 8 glucopyranose units and shaped like a hollow cone. They are potent phase transfer agents and have the rare property of being non-polar on the inside of the cone and polar on the outside. This creates a pocket for non-polar substrates. While they often require chemical modification, like partial methylation of the hydroxyl groups, the modification is typically strait forward. The work has been recently summarized in reviews.[21,22] These cyclodextrins can be used as phase transfer agents, just like surfactants, which has been shown for a multitude of reactions. They can also stabilize nanoparticles in water or be the basis for nanogels amongst other possible applications. Hydroformylation reactions have been performed utilizing this system, an example result would be a yield of 61 % of linear aldehyde after just 6 h using a Rh/TPPTS catalyst at 80°C.[23]

2.2.3.3 Catalysis with polymer particles Functionalized, micelle-like polymer particles have been reported to act as phase transfer agents for multiphasic hydroformylation reactions. The work from the Vogt group, mainly conducted by K. Kunna and H. Nowothnick, has in fact been the starting point for this thesis.[24– 26] The concept uses polymer particles as a phase transfer agent for the liquid-liquid hydroformylation of mainly 1-octene. The particles have a non-polar polystyrene core and a polar polyethylene glycol shell and are also functionalized with cationic moieties. They were suspected to act as microreactors, solubilizing the substrate in their core while being suspended in the aqueous phase. It was shown that they undergo a beneficial interaction with the anionic TPPTS-Rh catalyst, as long as they bear cationic functionalization. This observation lead to the 10 proposition that they act as catalyst carriers. In all of the work, the work up process with the phase separation after the reaction was barely touched upon, however. This turned out to be a major issue, as was found out in this work. Other groups have used micelle-like polymer particles, where a triphenylphosphine (TPP) ligand was implemented in the non-polar core of a particle that also had a polar shell. The hydroformylation of 1-octene with this system lead to a turnover frequency (TOF) of 700 h-1 and fairly high linear to branched ratios of 3-6.[27] In later work the Rh and particle leaching was addressed by linking particles together. This brought the Rh leaching down to ca. 1 – 2 ppm in the organic phase with similar yields and TOFs.[28] Polymer particles with ligands that are not implemented in the structure but covalently bound to the surface are discussed in chapter 2.2.6.

2.2.3.4 Catalysis using weak surfactants Multiphasic liquid-liquid systems have been used with classic surfactants as described above. This can lead to high yields by reducing or removing mass transfer limitations. A possible downside however is the formation of micro or macro emulsions that are quite stable and that don’t really separate, even after days. A possible solution to this can be the use of amphiphiles, sometimes called weak surfactants. These enable good mass transfer under reaction conditions so while there is stirring and elevated temperature. The surfactants are weak enough however, to have the emulsions collapse after the reaction. One system has been presented by the group of David Cole-Hamilton and uses triethylammonium salts with a C8-chain, amongst other weak surfactants. Comparing that to the classic surfactant cetrimonium bromid (see Table 2) bearing a C16-chain, it seems that the non-polar part being half as long, makes the difference. Hydroformylation reactions have been conducted with promising results. As an example, with 1-alkyl-3-methyl-imidazolium bromide as a weak surfactant, and a TPPTS/Rh catalyst, a yield of 70 % of linear aldehydes, with a TOF of 900 and 0.5 ppm Rh-leaching into the organic phase could be achieved.[29] Another example is work on a multistep process for the synthesis of

Boscalid®, where diethylene glycol butyl ether (C4E2) is used as an amphiphile to enable mass transfer while having good phase separation after the reaction.[30]

2.2.4 Switchable, multiphasic catalysis approaches

An alternative way to approach catalysis with the goal to combine the advantages of molecular catalysts and product separation that leaves the catalyst intact, is the use of switchable systems. These systems are monophasic under reaction conditions and can be switched into a biphasic liquid-liquid system after the reaction, where the product becomes easy to separate. This is schematically shown in Figure 4.

Figure 4. Scheme of a polar catalyst containing phase and a substrate phase. Via a chemical or physical switch, e.g. a temperature increase, the system becomes homogeneous under reaction conditions. To separate the product, the system is switched back.

Different switchable systems exist, and it is in fact possible to switch other components instead of the solvent; for example the catalyst. An important difference to the previously mentioned multiphase systems with phase transfer agent, is the truly homogeneous reaction system. The overall principle is quite similar though; both use a liquid-liquid phase separation with a catalyst phase that is recycled.

2.2.4.1 Catalysis with super critical carbon dioxide Carbon dioxide has an interesting property, in that it has a very low critical temperature (31° C) and critical pressure (76 bar). That means that it becomes supercritical at relatively mild conditions, although it should be mentioned that other components in the system change those parameters.[12,31] One important industrial application is the extraction of caffeine from coffee, carried out with super critical CO2 (scCO2) as a solvent. After the extraction, the solvent scCO2 can be separated from the caffeine by simple depressurization. Supercritical carbon dioxide is a

12 viable, albeit very non-polar, solvent for chemical reactions. The option of switching it back to a gas by simple depressurization can for example allow the precipitation of a catalyst.[31] An analogue to the liquid/liquid/gas reaction system applied in the RCH/RP process or presented in this thesis could also be carried out using scCO2 instead of an organic liquid phase. Because scCO2 is fully miscible with gases, it then becomes a liquid/supercritical-phase system. The polar phase can also be an ionic liquid (IL).[32] Ionic liquids are salts that are liquid below 100 °C. The combination of IL and scCO2 is quite common, as ILs don’t have a relevant vapor pressure, and lead to a very good separation with the product phase. The combination has also been applied for hydroformylation reactions, even in a continuous process. A TOF of 517 h-1 with a l/b ratio of 3 and a very low Rh leaching of 0.01 ppm has been achieved with 1-octene as a substrate.[33] In later work the selectivity could be increased to a l/b ratio of 11.5 using Sulfoxantphos (see Figure 5) ligands and derivatives.[34] Sulfoxantphos is the sulfonated version of the highly selective Xantphos ligand.[35,36]

Figure 5. Sulfoxantphos, a highly selective, water soluble ligand for the hydroformylation of terminal alkenes. Ph = phenyl-rings.

2.2.4.2 Catalysis in thermomorphic multicomponent solvent systems Thermomorphic multicomponent solvent systems (TMS) are ternary mixtures with a temperature dependent miscibility gap. They can be used as reaction media for catalytic reactions and are monophasic under reaction conditions. Under separation conditions at low temperatures, they can be separated into a product phase and a catalyst phase.[37] The hydroformylation of long chain alkenes was carried out in such a TMS using the highly selective Biphephos ligand.[37] One possible issue with this system is the necessity of having solvents that are fully miscible with the substrate at one temperature and show a miscibility gap with the

13 product at another temperature. This requires fine tuning of the solvent system for each new substrate and solvent, and sometimes requires toxic solvents like dimethylformamide. In some cases, however, a TMS can be applied, where the solvents are water and 1-butanol. With these green solvents, a hydroformylation of 1-octene can be conducted in a continuous process, leading to a constant yield of 73 %.[38] One common problem with this system is the catalyst leaching, which is often around a few percent of the initial Rh content. This is equivalent to a few ppm of Rh in the product phase. In the described continuous process the Rh in the product phase was indeed 15 ppm. The continuous hydroformylation process of 1-octene with Rh/Biphephos can however be combined with a following nanofiltration, which has led to a yield of 70 % over 50 h while retaining 97 % of the initial Rh.[39] Another disadvantage worth mentioning is the inherent limitation of how much substrate can be present in a reaction, since it has to be mixed with two other solvents and usually changes its polarity after the reaction.

2.2.4.3 Catalysis with switchable polarity solvents or catalysts

The concept utilized in TMS can also be applied with switches other than temperature. CO2 can be used for its chemical or physical properties to switch solvent systems from one to two liquid

[40] phases. The physical property makes use of the very different solubility of CO2 in organic solvents and water. An organic solvent that solubilizes a lot of CO2 massively increases in volume and becomes much more non-polar, this can lead to a miscibility gap with previously miscible polar solvents. It can also be used to precipitate substances, for example a catalyst.

Organic/aqueous tunable solvents (OATS) are systems with water and an organic solvent that is miscible with water. In this mixture, a reaction can be carried out homogeneously. After the reaction, the system can be separated by introducing a moderate amount of CO2, which solubilizes in the organic solvent. By not being very soluble in the water though, this leads to a decrease in polarity of the organic solvent, and results in phase separation. This has been done for a multitude of reactions, often using either tetrahydrofuran (THF) or acetonitrile (ACN) with water as solvents.[41,42] The hydroformylation of 1-octene has been carried out in a THF/water system with a TPPTS/Rh catalyst. A yield of over 80 % over three runs could be obtained while having a Rh leaching below the detection limit of 1 ppm. Only the TOF of ca. 50 /h was a bit

[43] low. One disadvantage of this process is the separation at high pressures of CO2, 32 bar in the given example.

There are other options to separate monophasic solvent mixtures with the help of CO2 however. One example is the so called switchable water. It means a mixture of water and a solvent that is miscible with it, like t-butanol in the presence of amines, and of course a substrate. The introduction of CO2 at a low pressure (1 bar) leads to the formation of bicarbonate salts with the amines, increasing the ion strength in the water, and leading to a miscibility gap with the

[44] organic solvent and product. The process is fully reversible by simply bubbling N2 through the solution. It should be noted that the amines are always quite basic.

The principle of amines reacting with CO2 to form salts, which then change the polarity quite significantly, can also be used on the catalyst itself instead of on one of the solvents. A reaction can be performed in a homogeneous way, and after the reaction, the catalyst is turned into an ionic form via CO2, this process is reversible when bubbling N2 through the solution. This allows for an easy catalyst separation. Hydroformylation reactions of 1-octene have been done using this system.[45,46] A yield of 70 % with a Rh leaching of less than 1 ppm could be achieved with this system. One disadvantage of this process is the synthesis of the ligands, which can be challenging.

2.2.5 Catalysis in other multiphasic liquid/liquid systems

With switchable solvent systems, the reactions take place under homogeneous conditions. They still have properties of multiphasic systems however, as they offer advantages from having different phases after the reaction, which enables easier catalyst recycling. When working with multiphasic systems that are not monophasic under reaction conditions, mass transfer is often an issue. The use of phase transfer agents can help with that problem, as discussed earlier. There are other interesting reaction systems however that don’t use those. Mass transfer of the substrate to the catalyst phase has to happen via diffusion in this case however, see Figure 6. This can limit the process in regard to the substrates that are available and can lead to mass transfer limitations.

Figure 6. Multiphasic reaction system with a polar catalyst-containing phase and non-polar substrates and product.

2.2.5.1 Catalysis utilizing ionic liquids Ionic liquids (IL) are salts that are liquid below 100 °C, although they often are highly viscous. They generally have a negligible vapor pressure, and a lot of properties, like polarity, can be tuned by using different anionic or cationic parts. While they can be somewhat expensive, the recycling of the ionic liquids might be so efficient that the initial cost becomes irrelevant. They

[47] can be applied in catalysis in multiple ways and an IL/scCO2 system has been described earlier. A special case for multiphase catalysis with homogeneous catalysts is the supported ionic liquid phase system (SILP).[48] It uses a solid support with a thin layer of ionic liquid. In this IL layer, a molecular catalyst is solubilized. This allows the use of selective catalysts that are immobilized without being covalently or even electrostatically bound to a support.[49] To avoid leaching of the IL, the substrate and product are ideally in the gas phase. An example for that would be the hydroformylation of 1-butene with Rh-diphosphite catalysts supported in an ionic liquid.[50]

2.2.5.2 Multiphasic reactions without phase transfer agents Apart from the above mentioned RCH/RP process, which is limited to substrates with sufficient solubility in polar phases (water), it is also possible to modify the polar phase to make the

16 process accessible to e.g. long chain alkenes. By exchanging the aqueous phase with methanol this has been done for the Pd-catalyzed methoxycarbonylation of 1-dodecene.[51] The Pd- leaching into the product phase in this system is fairly high when using pure methanol. The addition of water to the polar phase however, did decrease the leaching a lot, with an expected but moderate decrease in TOF.

As mentioned in the discussion of the RCH/RP process, the solubility of long chain alkenes is too low for the process without PTAs, at least in the way it is performed in industry. A very interesting liquid/liquid multiphase system is, what the authors call, the “lean aqueous hydroformylation” (of long chain alkenes).[52–55] It is a hydroformylation concept like in the RCH/RP process, with an aqueous phase containing Rh/TPPTS and a non-polar substrate/product phase. The difference is that it uses long chain alkenes, like 1-octene. This has been done multiple times with the use of phase transfer agents, like surfactants, polymer particles, or cyclodextrins, as mentioned above. What makes the lean aqueous hydroformylation of long chain alkenes so interesting, is that it does not use any phase transfer agent. The main way to enable the otherwise very limited mass transfer, is by generating a large interface area between the aqueous and non-polar phase. One example of achieving this is by using a jet-loop reactor. The l/b ratios of up to 2.3 indicate that the active catalyst is indeed a Rh/TPPTS species, which is not soluble in the product phase. The catalysis is therefore likely happening at the interface. There is also literature suggesting that the interface is not a sharp plane, but instead reaches over a range of 10 to 20 μm at which the polar and non-polar solvent are both present at roughly equal amounts.[56] This would allow a pseudo homogeneous reaction, if a sufficiently large interface area is created by very high power input from the stirrer or mixing system.

2.2.5.3 Multiphasic hydroformylation of long chain alkenes, utilizing Pickering emulsions Suspended silica particles can be used to increase the interface for hydroformylation reactions with two different liquid phases. The silica particles can form a so called Pickering emulsion (PE) in a system with a polar and a non-polar liquid.[57,58] That means that they form a very stable emulsion with a large interface area, stabilized by the particles. An oil in water Pickering emulsion system has been applied for the hydroformylation of 1-octene with a Rh/TPPTS catalyst leading to a TOF of 392 h-1, a regioselectivity of 79 % and a l/b ratio of 2.6 .[59] A positive effect from cationic functionalization of the silica particles was observed, as with the previously mentioned similar system with polymer particles. The separation after the reaction was not discussed however. The very high stability of the PEs, does make it challenging for a process however. A possible solution to this problem was presented, where the particles would be modified to result in a water in oil PE, which would allow for a filtration of the stable PE, allowing the retention of the catalyst.[60,61]

2.2.6 Catalyst immobilization and colloids as catalyst carriers

Homogeneous catalysts are desired, partly because of the atom efficiency, as every metal atom can be catalytically active. Every catalytic center is also expected to have the same properties, leading to the same selectivity. This is different with classic heterogeneous catalysts, as the surface of say Rh nanoparticles contains atoms with different properties. The ones on edges or steps on the surface will react differently than the ones on a flat surface. This usually decreases the selectivity of the catalyst. One option of getting rid of this problem, while still maintaining the advantage of easy catalyst separation and recycling, is the immobilization of homogeneous catalysts. One option is to electrostatically immobilize a homogeneous catalyst, as it has indeed been done in previous work with polymer particles.[24,25] Ligands can also be immobilized on activated carbon, where a TPPTS ligand can be used to immobilize a Rh-TPPTS catalyst for hydroformylation reactions.[62] The solid support can also be a resin. This has for example been done to immobilize a Pd-TPPTS catalyst for hydroxycarbonylation[63] or a Rh-TPPTS catalysts for hydroformylation reactions.[64] The catalyst can also be covalently bound, often on a silica

18 support, overall there are multiple immobilization options.[65,66] Ligands can also be immobilized on polymer particles in a covalent way. An example for that would be the immobilization of a transfer hydrogenation catalyst on polystyrene particles.[67] Other polystyrene particles have been functionalized with brushes, similar to the ones used in this work, but non-polar. In that work the catalyst is an organic catalyst based on tertiary nitrogen centers. The application of it was the acylation of secondary alcohols and the Baylis-Hillman reaction.[68]

Molecular catalysts can also be modified with large ligands, blurring the line between homogeneous and heterogeneous catalysts. These catalysts can be easily separated by filtration. One option is the modification of a ligand with dendrimers, which are large, star- shaped, hyperbranched molecules.[69] A hydroformylation of 1-octene has been conducted with a dendrimeric ligand, with full conversion and chemoselectivity, however a low l/b ratio.[70] In the described system the presence of heterogeneous catalysts could be shown. That is probably the reason for the low selectivity and a big disadvantage of the system. Another way of enlarging ligands, is the modification with a polyhedral oligosilsesquioxane (POSS) unit that represent rigid, cage-like structures. Modified ligands have for example been used to perform a metathesis reaction while separating the catalyst with a membrane.[71]

2.2.7 The best multiphasic approach for a catalytic reaction

With the presented wide array of solutions for multiphasic catalysis with molecular catalysts, the question arises, which one is the best? The answer is that this strongly depends on the situation. The RCH/RP process is applied on a large scale in industry, but even there it is not clearly the best, as other alternative processes are also operated.[11] All of the described processes have their advantages and disadvantages, some of them are mentioned in Table 3.

Table 3. Advantages and disadvantages of different multiphasic reaction systems with homogeneous catalysts. System Advantages Disadvantages Liquid/liquid without Easy product separation and Mass transfer problems for phase transfer agents catalyst recycling substrates with low solubility in the catalyst phase Liquid/liquid with Close to homogeneous conditions Can lead to leaching of PTAs, surfactants complex systems, chemical inertness with PTAs required Liquid/liquid with Flexible system that can be tuned chemical inertness with PTAs cyclodextrins by modifying the PTAs required, often requires modification of PTAs Liquid/liquid with Flexible system with low leaching Requires synthesis of polymer polymer particles particles, chemical inertness with particles required Thermomorphic Homogeneous catalysis New miscibility conditions for multicomponent each substrate/product, leaching solvent systems problems Organic/aqueous Homogeneous catalysis Separation not always very good, tunable solvents separation has to be done under pressure Switchable water Homogeneous system, simple Basic system, separation not switching necessarily good Pickering emulsions Flexible system Requires filtration as an with silica particles additional separation step Super critical CO2 Excellent and simple separation High pressures required Ionic liquids / super Low leaching and very good Requires high pressures and critical CO2 phase separation requires separation of CO2 and gaseous components (like syngas) Supported ionic liquid Pseudo heterogeneous Can be complex, some ILs are phase catalyst/support leads to very expensive, IL can leach if easy catalyst separation continuous phase is liquid Switchable polarity Truly homogeneous catalyst Basic conditions, catalyst catalyst synthesis required 20

With all those options, it seems difficult to know which system might be attractive for a reaction, as some of them might be better than simple homogeneous or heterogeneous setups. There is no simple way of finding a potentially better approach for a reaction. Some can obviously be excluded, like switchable polarity water setup with a base labile product, but the other way around is quite difficult. A guideline on how to find out whether a reaction can be performed in one of these systems is being proposed in Chapter 3.4.

2.3 The hydroformylation reaction.

The hydroformylation reaction, also known as the oxo process, is a reaction to obtain aldehydes from alkenes. The other substrates are CO and H2, usually in a 1:1 molar ratio, together called synthesis gas. In industry it is one of the largest scale reactions that uses homogeneous catalysts; the annual production in 2012 was over 12 million tons.[72] The net reaction can be seen in Scheme 1. Typically, terminal alkenes are the substrates, and linear aldehydes are usually the desired products.

Scheme 1. Hydroformylation reaction of a terminal alkene to either a linear or branched aldehyde.

The linear product (l) is formed preferably, according to the rule of Keulemann, even without a ligand, the other one is called the branched product (b).[72] Ligands change the selectivity, and phosphine ligands are usually employed to achieve higher linear/branched (l/b) ratios. When using linear alkenes and triphenyl phosphine or its derivatives, the l/b ratio is also influenced by the substrate. Short chain alkenes generally lead to higher l/b ratios than longer chain alkenes. The catalytic cycle of the reaction for a terminal alkene is shown in Figure 7.

Figure 7. Catalytic cycle of the hydroformylation reaction for a terminal alkene, L is typically a phosphine ligand, like TPPTS, R is for example an alkyl chain[73]

It is important to point out that a lot of the steps are reversible and a lot of other equilibria are relevant even if they are not directly in the catalytic cycle. Some important equilibria are shown in Scheme 3. Different Rh species are shown, of which all but c) can enter the catalytic cycle shown above, after dissociating a CO ligand.

Scheme 3. Rh species that are formed based on especially CO and L concentration, where L is a phosphine ligand.

The Rh species shown are formed from a precursor, but that is a fast reaction and not relevant for the further discussion. In Scheme 3 species a) is often a resting state of the Rh complex. It is however not catalytically active. In a CO dissociation step it forms the active, selective catalyst that is the starting point for the classic cycle shown in Figure 7. The Rh species underlies another equilibrium however. It can lose a phosphine ligand and gain a carbonyl ligand. That can happen up to two times, resulting in b), the opposite can happen, resulting in the catalytically inactive c). The Rh-carbonyl species b) is highly active, but quite unselective. When utilizing a polar TPPTS phosphine ligand, it is very important to note that the polarity of the Rh-complex changes from polar, so water soluble, to non-polar and therefore being soluble in non-polar solvents. In a biphasic system as described above, the active, but unselective catalyst species b) could then enter the substrate phase and act as a truly homogeneous catalyst.

Depending on the ligand, substrate and temperature, different steps in the catalytic cycle can become rate determining.[74] Even solvents have an influence on the reaction equilibria.[75] Electron richness on the β-position of the alkene, leads to more coordination of that carbon atom to the metal center and therefore more branched aldehydes. The +I-effect of a long chain alkene or the adjacent phenyl group in styrene are examples for that. They lead to higher amounts of branched aldehydes, and in the case of styrene, the branched aldehyde is in fact the major product. Internal double bonds can, depending on the molecule, also lead to different products. Internal double bonds are less reactive however. The reactivity of double bonds, depending on their position is:

Terminal > internal > terminal branched > internal branched > quaternary

Different metals can be used for the hydroformylation reaction and they deploy different activities. Rhodium is by far the most active one and is preferred, as mild conditions still allow high reaction rates, while also leading to high selectivities. The reactivity of different metals for the hydroformylation reaction is:[11]

Rh ≫ Co > Ir, Ru > Os > Pt > Pd ≫ Fe > Ni

While Rh is generally catalytically more active, Co is sometimes employed for different reasons. It is a lot cheaper than Rh and also much more robust towards poisons. Co catalysts are also 23 better suited for a feedstock with a mixture of internal and branched long-chain olefins. A high hydrogenation activity of Co catalysts can be used as an advantage, when the immediate reduction of the aldehydes to alcohols is desired. Other metals are not well explored as catalysts. [11] With any possible catalyst, different side reactions can occur. These are shown in Scheme 4.

Scheme 4. Hydroformylation reaction and common competing reactions leading to undesired products. a) hydrogenation b) hydroformylation to either linear or branched aldehyde c) isomerization d) aldol condensation of formed aldehydes

The hydroformylation reaction is usually competing with side reactions, which are isomerization, hydrogenation and aldol condensation. In the case of long chain alkenes, the isomerization can of course lead to multiple side products which are in an equilibrium.[76] A fast reaction rate can therefore often increase the selectivity by simply removing all of the substrate before it can isomerize or be hydrogenated.

3 Results and discussion 3.1 Polymer particle synthesis, properties and characterization

The content of this chapter describes the synthesis of micelle-like polymer particles, their properties and their characterization. Chapter 3.2 will then deal with the application of these particles in multiphasic hydroformylation reactions. The general idea is to synthesize particles that can act as phase transfer agents and catalyst carriers for anionic catalysts, see Figure 8.

Figure 8. Synthesis of polymer particles that are then applied as phase transfer agents for catalytic, multiphasic reactions, mainly hydroformylation reactions.[77]

3.1.1 Role of the monomers

Micelle-like polymer particles have previously been reported to act as PTA. The particles have been functionalized in different ways to act as catalyst carriers.[24,25] For this work we chose cationic functionalized particles, as these undergo a beneficial interaction with the very common anionic TPPTS ligand. The particles are synthesized in an emulsion polymerization containing four monomers, which are all styrene derivatives. The initiator used is VA86, a water soluble azo-initiator that can be seen in Figure 9.

Figure 9. VA86, a water soluble azo- initiator

It decomposes on heating, releasing nitrogen and forming radicals. It is fairly stable at low temperatures, but starts forming radicals very quickly when added to water and heated to 80 °C. The monomers used to form the particles are styrene, divinylbenzene (DVB), a styrene derivative with a polyethylene glycol (PEG-monomer) functionalization and a styrene derivative that is a salt (SS). These monomers can be seen in Figure 10, the PEG-monomer has a polyethylene glycol (PEG) chain with an average molecular weight of 2000 g/mol.

Figure 10. Monomers used for the synthesis of the polymer particles. Monomers left to right; Styrene, DVB, PEG monomer and salt-monomer.

Two of these monomers, styrene and DVB form the nonpolar core of the particles. Styrene is the main component in terms of molar ratio, while usually DVB is used only at 1.5 – 4 mol%. The DVB monomer with its two polymerizable double bonds leads to cross linking in the core of the particles and gives them stability. The stability could be shown by synthesizing particles with very low amounts of DVB, which would dissolve in organic solvents, instead of staying stable. The two polar monomers were expected to go to the surface of the particles, and indeed evidence for this was found in zeta-potential measurements and AFM-measurements, respectively. The cationic salt monomer was shown to lead to particles that can interact with anionic TPPTS ligands and bind, or carry them. This will be discussed in detail in Chapter 3.1.5, 26 which deals with the properties of the particles. The PEG-monomer has a non-polar part, namely the polymerizable styrene moiety while also containing a long PEG part with an average molecular weight of 2000 Dalton. The PEG part is polar and well water soluble at RT and at the polymerization temperature of 80°C. This leads to the micelle-like structure of the particles with a nonpolar core and a polar shell of PEG-chains, making the polystyrene based particles fully suspendable in water. The PEG-monomer was shown to be surface active and to have a critical micelle concentration (cmc), which means it can act as the necessary surfactant during the emulsion polymerization process.[78] This was checked using surface tension (SFT) measurements and can be seen in Figure 11. The styrene-salt is also surface active and might act as a co-surfactant, indicated by obtaining huge particles and significant agglomeration when not using the SS-monomer.

Figure 11. Surface tension measurements of the PEG- monomer[77]

The cmc of the PEG-monomer was found to be around 10 mmol/l. This means that the reactions that were carried out had a concentration above the cmc, with cPEG = 27 mmol/l in most reactions. To conclude, the styrene forms the core of the particles as a cheap polymerizable monomer and DVB adds stability. The PEG-monomer enables the emulsion polymerization in water without the need for traditional surfactants and leads to the particles being suspendable in water. Finally, the salt monomer seems to help with the polymerization as well as stability and gives the particles catalyst carrying properties.

3.1.2 Monomer conversion during the polymerization reaction

In literature, the synthesis of the polymer particles was described in a way where the initiator was added second to last and the PEG-monomer last.[24,25] This is counterintuitive, considering it was shown that the PEG-monomer likely functions as a surfactant during the emulsion polymerization and micelles need to be formed to start an emulsion polymerization.[78] To learn more about the consumption of the monomers, their conversion has been investigated. A fast conversion of monomers indicates that a mixing of all the monomers before adding the initiator would be preferred. To investigate the consumption of monomers during the polymerization, different methods had to be applied, since some monomers are polar and some are non-polar. The non-polar monomers styrene and DVB have been extracted with diethyl ether from samples that were taken at different points during the reaction. The samples were then analyzed by gas chromatography (GC). Both non-polar samples were found to have more than 99 % conversion after 10 min. For the water soluble monomers, the liquid parts of the samples have been evaporated and the residues were solubilized in deuterated water and analyzed by proton nuclear magnetic resonance spectroscopy (1H-NMR). More than 91 % of the styrene-salt was converted after 10 min, while a similar consumption of PEG-monomer of 90 % was already reached after just 1 min. For more details see Figures A1-A3 in the appendix. This means that the reaction of monomers is very fast in the beginning, so adding initiator before the PEG-monomer might lead to particles where the distribution of monomers over the particles is not very even, as some monomers might have already reacted when the last monomer is added.

3.1.3 Optimization of the polymerization reaction

When synthesizing polymer particles in the beginning of this work, there were multiple issues, leading to problems with agglomeration and reproducibility. One problem was that stainless steel autoclaves have sometimes been utilized in the early batches of particles synthesized during this project. Steel autoclaves however lead to agglomeration, so glass autoclaves have to be recommended for the synthesis of these particles. Another common problem was the sensitivity of the polymerization towards air contamination. For reproducing these particles, thorough work is advised, although nitrogen was sufficient as an inert gas, and no argon was

28 required. In the protocol of the synthesis reported in prior work with these particles, which was also applied in the early attempts of this work, the initiator was added before the PEG monomer (PEG-last-method). [24] It could be shown that the addition of the initiator after adding the PEG monomer did not pose problems (initiator-last-method), while facilitating the particle synthesis in multiple ways (see Table 4). The reaction setup for the PEG-last-method is also more complicated, as solubilizing all the monomers quickly can be an issue. Solubility problems in the beginning can be detrimental, since the first minutes of the polymerization are especially important, as shown in the previous chapter. In addition to an easier setup which reduces the danger of air-contamination, the Initiator-last-method leads to no visible agglomeration after the reaction, which was common in the old synthesis.

Table 4. Influence on agglomeration by monomer/initiator addition. Monomer composition: Styrene mol% = 72; DVB mol% = 4; Salt-monomer mol% = 20; PEG-monomer mol% = 4 Method Hydrodynamic radius by Agglomeration DLS in nm PEG-last 130 Visible agglomeration Initiator-last 48 No visible agglomeration

While still following the recipe from literature with the addition of the PEG-monomer after the initiator, interesting trends could be observed when varying the amount of PEG-monomer and initiator (Table 5). It should be noted that the reproducibility for the PEG-last method was still fairly high.

Table 5. Influence of PEG-monomer on particle size for the PEG-last method mol% of monomers Hydrodynamic Entry Styrene- PEG- Styrene DVB radius by DLS in nm salt monomer 1 76 2 20 2 240 2 74 2 20 4 159 3 70 2 20 8 47

In these cases, the PEG-monomer had a huge influence on the size of the resulting particles. As expected, more PEG-monomer led to smaller particles, as it means that during the

29 polymerization reaction more surfactant was available, stabilizing a higher number of micelles, which form more particles and therefore lead to smaller sizes. Another interesting influence was observed when varying the amount of cross linking agent (Table 6). The more DVB is used, the smaller the particles get. The influence of this is however less significant than that of the PEG monomer.

Table 6. Influence of DVB on particle size with the PEG-last method mol% of monomers Hydrodynamic Entry Styrene- PEG- Styrene DVB radius by DLS in nm salt monomer 1 74 2 20 4 159 2 72 4 20 4 130 3 70 6 20 4 105

3.1.4 Synthesis of polymer particles with different compositions

For the rest of this work the initiator-last method was chosen, as this lead to decreased solubility issues and simplified the experimental setup, as well as removing the visible agglomeration. For this improved method the influence of different monomer ratios was investigated, which is also published[77], and discussed in detail in the following chapter. In short, it shows that the influence of variations of the crosslinking agent DVB and the PEG- monomer is not very big with the initiator-last method. Size and ζ-potential are roughly the same for the investigated ratios. Furthermore a different commercial DVB-source was also investigated, as high purity DVB is 600 times more expensive than the 55%-purity DVB. According to the supplier, the impurities of the cheaper DVB are 4-ethylvinylbenzene and 3- ethylvinylbenzene. These are expected to react similar to styrene, and not to have a relevant impact because of the low concentration. The cheaper DVB proved to be perfectly viable, and gave very similar results. Some investigated particle compositions are listed in Table 7.

Table 7. Composition of the different polymer particle suspensions Composition (mol %) Agglomeration Sample PEG- S DVB SS monomer LX1 73 3 20 4 No LX2 70.5 1.5 20 8 No LX3 74.5 1.5 20 4 No LX4 93 3 0 4 Yes LX5[a] 73 3 20 4 No S = styrene, DVB = divinylbenzene, SS = styrene derivative salt (p- vinylbenzyl)trimethylammonium tetrafluoroborate; [a] DVB purity: 55%

An interesting influence of the surface active salt-monomer could be observed. Particles synthesized without it were much bigger and showed agglomeration during the particle synthesis. This can be seen as an indicator that the salt-monomer acts as a co-surfactant, stabilizing the micelles during the emulsion polymerization. The particles without the salt- monomer were also visibly different, see Figure A4 in the Appendix.

3.1.5 Characterization of the polymer particles

The particles were characterized by dynamic light scattering (DLS), atomic force microscopy (AFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and zeta potential (ζ-potential) measurement. DLS, AFM, TEM and SEM give insight on the particle size and shape, while the ζ-potential measurement gives information about the electrostatic potential of the particles. In further experiments, the properties of the particles being catalyst carriers have been investigated.

3.1.5.1 Characterization of size and shape The ζ-potential was found to be around +50 mV for all particles, except for the one without the cationic salt monomer, where the ζ-potential was around 0 mV. This confirms that the cationic salt does influence the particles majorly. It suggests that the ionic monomers are indeed incorporated in the surface of the particles, as expected, and create a poly-cationic particle. It furthermore shows that the shell of the particles with PEG-chains does not shield the cationic groups entirely. A ζ-potential of above 30 mV is considered strong enough for electrostatic

31 stabilization, so the cationic functionalization does also make the particles more stable towards coagulation.[79] The results of all measurements can be found in Table 8.

Table 8. Zeta Potentials and diameters (D) of the polymer particles obtained with different characterization techniques ZP (ζ) DLS AFM SEM TEM Sample [a] (mV) Dh (nm) D (nm) D (nm) D (nm) LX1 + 51.1 105 ± 5 78 ± 14 31 ± 2 31 ± 4 LX2 + 47.7 126 ± 2 79 ± 12 31 ± 4 32 ± 3 LX3 + 53.7 105 ± 5 79 ± 13 33 ± 3 38 ± 6 LX4 - 3.0 217 ± 13 - - - LX5 + 48.3 95 ± 1 72 ± 7 30 ± 3 32 ± 3

[a] Dh: Hydrodynamic Diameter

For all particles, the size and shape was similar, with the exception of LX 4, which is the one without the cationic monomer. This confirms again that the salt-monomer stabilizes the polymerization process, which could already be qualitatively confirmed by observing agglomeration during the polymerization process.

The different measuring techniques showed different particle diameters, as can be seen in Table 8. They don’t vary by too much though, and the different observed sizes can be explained when looking into the measuring techniques. TEM and SEM detect the electron dense polystyrene core, and therefore show the size of the core, which is around 30 nm in diameter. SEM and TEM images are shown in Figure 12. As can be seen, the particles appear roughly spherical.

Figure 12. Left: TEM image of the polymer particles, right: SEM image of the polymer particles[77] 32 The AFM measurements gave particle diameters of around 80 nm. For this, it has to be considered that the AFM detects the core plus the shell. This shows that the core plus shell seem to have an 80 nm diameter, while the core itself has a diameter of around 30 nm, which in fact can also be observed by AFM, when using the phase mode, see Figure 13.

Figure 13. AFM images of the polymer particles in hight mode (left) and in phase mode (right)[77]

The core and shell of the particles is shown in more detail for a single particle in Figure A5 in the appendix. The higher density of the polystyrene-core makes it appear darker in that image than the lighter color of the PEG-shell.

This leaves the DLS measurement, which is conducted in an aqueous solution, and does not only show the particle including its PEG-shell, but also their hydrodynamic radius. In addition to that, the PEG chains are likely extended in the aqueous phase, instead of collapsed, when measuring the dry particles with AFM. The resulting diameter of around 100 nm therefore makes sense. The different detected diameters and the corresponding parts of the particles are schematically shown in Figure 14.

Figure 14. Simplified image of the particle and the parts of it that the different measuring techniques can detect.

3.1.5.2 Catalyst carrier properties The particles are suspected to act as catalyst carriers in previous work, where a beneficial interaction of the cationic groups with anionic ligands has been described for the multiphasic hydroformylation of long chain alkenes.[24] The positive ζ-potential given by the cationic moieties suggests an interaction with the anionic TPPTS ligands. To prove the concept, the catalyst precursor [Rh(acac)(CO)2] (acac = acetylacetone) and 6 equivalents of TPPTS were dissolved in an aqueous dispersion with polymer particles (250 mg of particles in 10 ml of water). The resulting suspensions were then transferred to centrifuge tubes containing a cellulose membrane with a 10.000 Da molecular weight cut-off (mwc), and centrifuged at 2500 rpm for one hour. The solutions that passed the membrane were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-OES) to quantify the non-retained rhodium and phosphorous. The same experiments were carried out using pure water instead of polymer particle suspensions. In that case, the rhodium catalyst and the excess of TPPTS ligand were not retained at all by the membrane and detected quantitatively by ICP-OES. The qualitative results can be found in the appendix, Figure A6. As can be seen, the particles seem to retain the Rh- TPPTS catalyst when they have the cationic functionalization, and otherwise don’t. This has indeed been confirmed with ICP-OES analysis, see Table 9. 34

Table 9: analysis of the filtrate of the catalyst carrier experiment No particles LX5 LX4 (no salt monomer) % of initial Rh > 95 4 > 95 in the filtrate % of initial P 91 9 90 in the filtrate Conditions: 10 ml of water and 1.5 mM [Rh(acac)(CO)2], 9 mM TPPTS and 25 mg/ml polymer particles were centrifuged with 2500 rpm through a 10.000 Da mwc membrane for 1 h.

The cationic functionalized particles retained most of the catalyst and excess of ligand. The anionic, sulfonated TPPTS ligand of the catalyst seems to be electrostatically attached to the polymer particles bearing cationic ammonium groups. What’s interesting about that is that the counterions of the cationic groups and ligands are still in solution. Assuming the salt monomer was completely incorporated in the structure of the particles during the polymerization, the concentration of ammonium salt in the LX1 and LX5 dispersions would be 5 times higher than the TPPTS concentration in the solution. In addition to that, the local concentration of cationic groups on the surface of the particles is higher than it would be in solution. A likely driving force for this electrostatic immobilization is the possible multiple site interaction between the particle surface and the catalyst complex. Each TPPTS ligand bears three anionic sites, and each metal center can have multiple phosphine ligands, as portrayed in Figure 15.

Figure 15. Multiple site, electrostatic interaction between the numerous anionic [80] moieties of Rh-TPPTSn catalysts and the polycationic particles, n = 1-4 35

It is important to mention that in a catalytic experiment the amount of rhodium and phosphine that might be lost would be almost negligible, since the non-retained anionic catalyst and ligand should not be soluble in the non-polar phase (substrate and products).

3.2 Hydroformylation reactions with polymer particles as phase transfer agents

The polymer particles described in Chapter 3.1.4 were applied in multiphasic, catalytic reactions. In most cases the hydroformylation of 1-octene was investigated, see Scheme 3. For long chain alkenes like 1-octene, the linear product is the desired one.

Scheme 3. Multiphase hydroformylation of 1-octene with the branched (b) and linear (l) aldehyde as products

It is important to note that, while it is known that the reaction works in principle, the recycling, product separation and phase behavior have not been documented or investigated before. They are crucial however, when designing a reaction process. When looking into phase behavior and separation, severe hurdles were found, namely the formation of Pickering emulsions. In this chapter the catalytic performance as well as the phase separation and recycling will be discussed. The combination both aspects is vital when wanting to turn the reaction system in to a larger scale process. As a side note; the purification of especially alkenes is in fact quite important for these reactions. Small amounts of peroxides are quite common even in fresh, commercial alkenes. These can be removed by an alumina column, and can otherwise oxidize the phosphine ligands.[81]

3.2.1 Multiphasic hydroformylation reactions with polymer particles with different compositions

The polymer particles with different compositions that have been described and characterized earlier have been utilized as phase transfer agents. The reaction of choice to investigate most conditions is the hydroformylation of 1-octene, mentioned earlier (Scheme 3). The influence of different compositions on the catalysis seems minor for the synthesized particles and they all seem viable, see Table 10.

Table 10. Multiphasic hydroformylation of 1-octene using polymer particles as phase transfer agents Entry Particles Conversion (%) l : b TOF at 10% conv. (h-1) 1 LX1 82 2.6 300 2 LX2 85 2.6 343 4 LX3 76 2.6 272 5 LX5 75 2.6 272 Reaction conditions: 0.03 mmol [Rh(acac)(CO)2], 0.18 mmol TPPTS, 150 mmol 1-octene, [C]:[L]:[S] = 1:6:5000, 15 mmol n-dodecane as internal standard. 500 mg of particles, 20 0 ml H2O. 80 C, 700 rpm, 100 bar CO:H2 (1:1), 22 h.

The hydroformylation reactions with the different particles had complete chemoselectivity in these reactions. So no hydrogenation, isomerization or other side reaction product could be detected by GC analysis. Standard ratios of linear to branched aldehydes for monodentate phosphine ligands and 1-octene as a substrate were obtained. The Rh leaching into the organic phase after the reaction was investigated with ICP-OES and was found to be below 0.5 ppm. None of the particles agglomerated under reaction conditions, which is a problem that occurred with earlier particle generations. Because all the compositions were similar in performance under catalytic conditions, LX5 was chosen, as it uses less pure and much cheaper DVB as a monomer than the other particles, which makes it more attractive for a larger scale process. The pH-Value has generally not been monitored for these reactions, as it has been found in previous work, that for very similar conditions, the pH-value would not vary too much and also not have a huge influence between 5 and 9.[82]

3.2.2 The challenge of the phase separation

When starting the work with these particles, an interesting issue came up that is often ignored in literature: the phase separation after the reaction. While the concept states that the product is separated with a simple decantation after the reaction, this is not possible with the conditions given in literature for the polymer particle system. The mixture does not fully separate into a clear product phase and an aqueous phase with catalyst, particles and excess of ligand. An aqueous phase can usually be found, however. Depending on the conditions, there is often no, or just very little visible product phase (see Figure 16).

Figure 16. Sample reaction mixture of a multiphasic hydroformylation of 1-octene with a Rh-TPPTS catalyst and polymer particles as PTA.

As can be seen, there is an aqueous phase on the bottom, which is turbid and yellow because of polymer particles and catalyst. On the very top there is some amount of clear phase that contains product, substrate and the utilized standard. In between however, there is a highly viscous slightly yellow phase. The stable viscous phases that form after reactions have been investigated using visual microscopy, showing droplets in a continuous phase that are pushed against each other without coagulating (appendix Figure A7). This is a strong indicator that the

38 emulsion is stabilized by some effect. Surfactants can stabilize emulsions, and the Rh-TPPTS catalyst is known to be surface active. However the emulsions in the reaction mixtures did not separate, even after months, an unusual stability. Because of the stability of the droplets in these emulsion, as seen in the microscopy images, as well as the emulsions being stable for months, we expect them to be Pickering emulsions. That means droplets that are stabilized by solid particles – the polymer particles used as phase transfer agents in this case. To gain more insight on the emulsions, artificial reaction mixtures were prepared from water, polymer particles, and the substrate of the hydroformylation reaction, 1-octene as well as the standard used in those reactions. To these mixtures, a hydrophobic or a hydrophilic fluorescent dye was added respectively. The macroscopic and microscopic pictures can be seen in Figure 17 and 18. The volume of aqueous phase to non-polar phase was kept at 3/1 in these cases, as then the macroscopic phases were visually easier to differentiate. It should be noted that no surface active Rh-TPPTS ligand is in this mixture, meaning that any stabilization of emulsions is very likely due to the polymer particles.

Figure 17. (left) Mixture of 1-octene, water and polymer particles, imitating the reaction mixture used in catalytic reactions. A fluorescent, hydrophilic dye, uranine, leads to a brighter colour. The emulsion phase is analysed by microscopy (right)

The samples were prepared using an ultrasonic bath. The mixture resulted in an aqueous phase with particles on the bottom, making it turbid, and hydrophilic dye, making it yellow. No yellow catalyst is present in these mixtures. On top of the aqueous phase, there is a viscous layer that contains the non-polar liquids, mainly 1-octene, but as can be seen from the color, it also

39 contains water, and therefore the yellow dye. In the microscopy image of the upper part, a bright continuous phase can be seen and dark droplets in it. Since a fluorescent dye was used in conditions where it appears brighter, the continuous phase seems to be the aqueous phase. This appears to be an oil in water emulsion. The same experiment was repeated with a non- polar dye, nile red, see Figure 18.

Figure 18. (left) Mixture of 1-octene, water and polymer particles, imitating the reaction mixture used in catalytic reactions. A fluorescent, hydrophobic dye, nile red The Emulsion phase is analysed by microscopy (right)

With the non-polar dye, some interesting effects can be observed. First of all, the aqueous phase is slightly colored. Pure water would not solubilize enough dye to be visible, so it seems that the polymer particles can solubilize a relevant amount of hydrophobic dye. The microscopy image was taken from the viscous middle phase, while there was also a non-polar upper phase. In this case the continuous phase was darker than the droplets, also suggesting that the dye and therefore the non-polar phase being the droplets. To conclude, the use of hydrophilic and hydrophobic dyes showed that, at least under the investigated conditions, the emulsion seems to be an oil in water Pickering emulsion.

3.2.3 Reaction optimization

Multiple parameters were optimized for the particle system. Optimization was done in regard to selectivity, yield, phase separation, required amount of catalyst, recycling and reaction rate. The

40 combination of these factors allows for a process design, and different applications in recycling runs are shown in Chapter 3.2.6.

3.2.3.1 Reduction of the amount of catalyst The ratio of Rh to ligand to substrate, Rh:L:S of 1:6:5000 was taken from literature[24] and gave good results. To see the influence of lower amounts of catalyst a series of reactions was conducted where the amount of Rh and ligand were cut in half multiple times, see Table 11. The amount of substrate was kept constant for all reactions.

Table 11. Multiphasic hydroformylation of 1-octene with increasing substrate to catalyst ratio, reducing the amount of catalyst while keeping the amount of substrate constant TOF at 10% Entry [S]:[Rh] Conversion(%) Chemosel. (%) l : b conv. (h-1) 1 5000 87 99 2.6 347 2 10000 86 98 2.5 541 3 20000 90 96 2.4 1200 4 40000 93 90 2.3 2024 5 80000 96 85 2.1 3280 Reaction conditions: [Rh(acac)(CO)2], TPPTS, [L]:[Rh] = 6, 150 mmol 1-octene, 15 mmol n-dodecane as internal standard. 500 mg of polymer particles, 20 ml H2O. 80°C, 700 rpm, 100 bar CO:H2 (1:1), 22 h.

The conversion stayed high down to very low catalyst loading, although both chemo- as well as regioselectivity dropped noticeably at low amounts of catalyst. By-products were octene- isomers, with less than 1 % hydrogenation products. The fact that the TOF almost doubles when using half the amount of catalyst suggests a mass transfer limitation, although as can be seen in Figure 19 the reaction does not seem to be linear in the beginning, which would be expected for a mass transfer limited reaction.

100

60 [S]:[C] = 5000

40 [S]:[C] = 10000 [S]:[C] = 20000 [S]:[C] = 40000

Yield of aldehydes (%) aldehydes of Yield 20 [S]:[C] = 80000

0 0 5 Time (h) 10 15 20

Figure 19. Hydroformylation of 1-octene using polymer particles as PTA. The amount of substrate was kept constant, while the amount of catalyst was decreased, see Table 11

The loss in selectivity and yield with lower amounts of catalyst is also given in Figure 20. To preserve the precious metal Rh, it was decided to work with a S:C ratio of 40000, as a compromise between selectivity and saving in utilized Rh.

100 95 90 85 Conversion Chemoselectivity 80 Regioselectivity % 75 Yield Nonanal selectivity 70 65 60 55 0 20000 [S]:[Rh] 40000 60000 80000

Figure 20. Catalytic performance of the multiphasic hydroformylation of 1-octene using different ratios of substrate to catalyst, conditions see Table 1[80]

An interesting and welcome finding of these experiments was that the phase separation after the reaction improved drastically when lowering the amounts of metal and ligand. This is likely due to the surface activity of TPPTS and especially the Rh-TPPTS complex that stabilize emulsions by acting like surfactants. An image of the post-reaction mixtures can be found in the appendix (Figure A8).

In the experiments where the amount of Rh was lowered, the metal to ligand ratio was kept constant. This however does not mean that the metal center has the same amount of coordinated phosphine ligands, as not only the ratio but also the overall concentration of phosphine ligand is relevant for that. The decreased selectivity for lower amounts of catalyst is the expected result. To regain some selectivity at the cost of some reaction rate, the amount of ligand was increased with the [S]:[Rh] ratio of 40000 that was chosen earlier. In addition to that, the amount of particles was varied, as well as the stirring rate. The results of these reactions can be found in Table 12.

Table 12. Optimization of the multiphasic hydroformylation of 1-octene [PTA] Stirring Conv. Chemo-sel. TOF at 10% conv. Entry [L]:[Rh] l : b (mg/ml) (rpm) (%) (%) (h-1) 1 6 25 700 93 90 2.3 2024 2 20 25 700 59 98 2.5 1240 3 20 25 350 50 98 2.5 1076 4 20 35 350 73 97 2.5 1600 Reaction conditions: [Rh(acac)(CO)2], TPPTS, 150 mmol 1-octene, 15 mmol n-dodecane as internal standard, [S]:[Rh] = 40000, 20 ml H2O. 80°C, 100 bar CO:H2 (1:1), 22 h.

A decrease in stirring rate had two effects, it decreases conversion, as the mass transfer limitation is more pronounced, however it does improves the phase separation (see Figure A9 in the appendix). An increase of the amount of polymer particles had an inverse effect, increasing the conversion while making the phase separation just slightly worse. Conditions with a low stirring rate of 350 rpm and a particle concentration in the aqueous phase of 35 mg/ml were chosen for a lot of the following reactions as a compromise between observable reaction rate and phase separation. The conversion to aldehydes over time based on the syn-gas consumption can be found in Figure 21.

[L]:[Rh]=6; 25 mg/ml PTA; 700 rpm [L]:[Rh]=20; 25 mg/ml PTA; 700 rpm 80 [L]:[Rh]=20; 25 mg/ml PTA; 350 rpm [L]:[Rh]=20; 35 mg/ml PTA; 350 rpm

Yield to aldehydes (%) 20

0 0 5 10 15 20 Time (h)

Figure 21. Aldehyde yield vs. time in the multiphasic hydroformylation of 1-octene, end point from GC-results and the graph by gas uptake measurement see Table 12[80]

The linear gas uptake in Figure 21 clearly indicates a mass transfer limitation, which shows the trade of between reaction rate and phase separation.

3.2.3.2 Influence of modified ligands on multiphasic hydroformylation reactions Water soluble ligands are vital for this reaction system, but anionic ligands are expected to be generally viable since they can interact with the cationic particles. In literature is has been shown that TPP derivatives of the Danphos family are effective ligands for multiphasic hydroformylation.[83] These ligands bear electron withdrawing trifluoromethyl groups on some of the phenyl rings, while still being water soluble (Figure 22). Additionally mono- and di- sulfonated TPP ligands have been investigated.

Figure 22. Sulfonated ligands employed in the multiphasic hydroformylation of 1-octene.[80]

The conditions used were adapted from the optimization done earlier. Specifically catalyst ratios of [Rh]:[L]:[S] = 1:20:40000, a polymer particle concentration of 35 mg/ml and a stirring rate of 350 rpm were used. The low stirring rate was utilized to obtain a good phase separation. The results can be found in Table 13.

Table 13. Multiphasic hydroformylation of 1-octene with different ligands Entry Ligand Conversion (%) l : b TOF at 10% conv. (h-1) 1 TPPTS 73 2.5 1600 2 TPPDS 37 1.9 732 3 TPPMS 33 2.8 652 4 Danphos 56 2.9 1640 5 Dan2phos 46 4.6 1050 [Rh(acac)(CO)2], 150 mmol 1-octene, 15 mmol n-dodecane as internal standard, 700 mg of polymer [S]:[L]:[Rh] = 40000:20:1, 20 ml H2O. 80°C, 350 rmp, 100 bar CO:H2 (1:1), 22 h. Almost complete chemoselectivity towards aldehydes was observed for all reactions.

The Conversion to aldehydes based on the syngas consumption can be found in Figure 23. It can be seen that for TPPTS and Danphos, a similar TOF is found in the beginning, but the TPPTS does lead to a higher conversion. It should be noted that the gas uptake is generally not as reliable as the GC-data.

80 TPPTS TPPDS 70 TPPMS Danphos 60 Dan2phos

Yieldaldehydes to (%) 20

0 0 5 10 15 20 Time (h)

Figure 23. Aldehyde yield vs. time in the multiphasic hydroformylation of 1-octene with different sulfonated ligands, conditions see Table 13[80]

As can be seen in Figure 23, the sulfonate groups on the ligand seem to have a positive influence on the catalytic performance of the Rh-ligand system. As could be shown earlier, the particles are catalyst carriers and are also very likely go to the interface of substrate phase and catalyst containing aqueous phase. Multiple anionic sites on the ligand lead to an increased likeliness of the catalyst being electrostatically bound to the particles and therefore in close proximity of the substrate. This reduces mass transfer limitation and increases the rate of the reaction. This would explain, why the conversion increases with additional sulfonated groups on the ligand. The addition of trifluoromethylated groups makes the ligands more similar to a surfactant, as one side becomes quite nonpolar while one is charged. This could lead to more catalyst complexes at the interface, leading to higher conversion because of reduced mass transfer limitation. In addition, the trifluoromethylated group has a positive influence on the selectivity of the catalyst. TPP ligands that have electron withdrawing groups are weaker σ-donors and stronger π-acceptors. They lead to less electron rich metal centers.[84,85] The regioselectivity is therefore improved, which means that more of the desired linear aldehydes are formed.

3.2.3.3 Influence of chain lengths of linear alkenes with polymer particles Linear alkenes with different chain lengths have been investigated as substrates in the multiphasic hydroformylation with polymer particles as phase transfer agents. The optimized conditions used for 1-octene were utilized for the different substrates, see Table 14.

Table 14. Multiphasic hydroformylation of different long chain 1-alkenes Conversion Chemosel. TOF at 10% Entry Substrate l : b (%) (%) conv. (h-1) 1 1-Hexene 83 99 2.6 1873 2 1-Octene 73 97 2.5 1600 3 1-Decene 55 91 2.3 1024 4 1-Dodecene 36 92 2.3 744 Reaction conditions: 0.00375 mmol [Rh(acac)(CO)2], 0.075 mmol TPPTS, 150 mmol of substrate, [Rh]:[L]:[S] = 1:20:40000, 15 mmol of internal standard, 700 mg of PTA, 20 ml H2O, 80°C, 350 rpm, 100 bar CO:H2 (1:1), 22 h

The investigated substrates showed the results that are expected from literature[62], which means increasing reaction rate with shorter chain lengths, as well as increasing chemo- and 46 regioselectivity. The reason for the faster overall reaction for shorter chain alkenes is a higher solubility in the aqueous phase. The faster rate of the hydroformylation reaction for shorter chain alkenes leads to a higher chemoselectivity as the competing hydration and isomerization reactions are slower in comparison. The conversion to aldehydes over time based on the gas uptake can be found in Figure 24.

80 1-Hexene 1-Octene 70 1-Decene 1-Dodecene 60

Yieldaldehydes to (%) 20

0 0 5 10 15 20 Time (h)

Figure 24. Aldehyde yield vs. time in the multiphasic hydroformylation of different 1-alkenes, conditions see Table 14[80]

3.2.3.4 Influence of the concentration of polymer particles The influence of the polymer particle concentration was investigated, bringing interesting results. The previously optimized conditions utilize 35 mg of particles per ml. When repeating the experiments under slightly different conditions with a higher stirring rate, the difference between 25 mg/ml and 35 mg/ml turned out to not be that large. Decreasing the amount of polymer particles further, did however significantly lower the conversion, while keeping the selectivity at the same level, indicating the same active species but a less efficient mass transfer (see Table 15). When utilizing no polymer particles at all however, a very high conversion could be achieved. While the selectivity dropped noticeably, it did drop by an amount low enough to still have increased yield without particles compared to a system with particles. The fact that the reaction seems to work under these conditions without the need for phase transfer agents was surprising. Further investigations of these results can be found in Chapter 3.3. It should be 47 noted that the jump in selectivity and conversion from low amounts of particles to a particle- free system already indicates a different mechanism. The byproducts without particles were isomerization products.

Table 15. hydroformylation with a varying amount of polymer particles as PTA. PTA X Schem. Sregio. l/b Y TOF (10 % X) (mg/ml) (%) (%) (%) (%) (1/h) 0 99 90 61 1.5 54 4364 5 39 95 71 2.5 27 851 10 57 >99 71 2.5 41* 1412 25 69 94 70 2.3 46* 1534 35 63 95 70 2.4 42* 1408 Reaction conditions: 0.00375 mmol [Rh(acac)(CO)2], 0.075 mmol TPPTS, 150 mmol of substrate, [Rh]:[L]:[S] = 1:20:40000, 15 mmol of internal standard, 20 ml H2O, 80°C, 1750 rpm, 100 bar CO:H2 (1:1), 22 h. * As mentioned in Chapter 3.2.3.5, the high stirring rate in combination with polymer particles lead to higher variation in GC results.

As can be seen in Figure 25, the polymer particles are required under these conditions to achieve the selectivity that is usual for monodentate phosphine ligands. When using the particles, a higher concentration generally leads to higher reaction rates, which is to be expected, as it could be shown that they act as phase transfer agents.

100 0 mg/ml PTA 90 5 mg/ml PTA 80 10 mg/ml PTA 70 25 mg/ml PTA 60 35 mg/ml PTA 50 40 30

Yield of aldehydes (%) aldehydes of Yield 20 10 0 0 5 10 Time (h) 15 20

Figure 25. Aldehyde yield vs. time in the multiphasic hydroformylation of 1-octene, using different amount of polymer particles, conditions see Table 15

3.2.3.5 Influence of the stirring rate It could be shown that mass transfer can be a relevant problem for the reaction system with polymer particles as phase transfer agents. The concentration of particles does have an influence on that, and so does the stirring rate. In a systematic approach it was tried to get information on high stirring rates which would be interesting for a process that does not care about the formation of Pickering emulsions, for example because they are destroyed by microfiltration. As can be seen in Table 16, an increase in stirring rate generally does seem to increase the conversion, while not influencing the selectivity. However, high stirring rates brought massive problems with them. The amount of liquid that could be recovered after the reaction with 1750 rpm was significantly lower than expected (see Figure A10 in the appendix). The loss of reaction mixture was investigated by using a transparent exhaust tube after the reaction, as seen in appendix Figure A10. It turned out that the amount of Pickering emulsion was massive and during depressurization the emulsion was carried out of the exhaust pipe, which lead to an unrecoverable loss of reaction mixture. This also contaminates the reactor periphery. The lowered detected conversion at 1750 rpm is possibly due to a changed ratio of standard and product/substrate, as these components leave the reactor in an uncontrolled way. The results are therefore expected to have a higher error than the usual results. High stirring rates (> 1000 rpm) therefore seem highly unadvisable for a system using the polymer particles utilized in this work.

Table 16. Hydroformylation with particles and varying stirring rates. Stirring rate X Schem. Sregio. l/b Ylin. ald. (1/min) (%) (%) (%) (%) 350 58 97 71 2.4 39 700 73 95 70 2.4 49 1050a 83 95 70 2.3 55 1750a 63 95 70 2.4 42 Reaction conditions: [Rh(acac)(CO)2], TPPTS, [L] : [C] = 20, 150 mmol 1-octene, [S] : [C] = 40.000, 15 mmol n-dodecane as internal standard, V(H2O) = 20 ml, 35 mg/ml PTA, T = 80°C, psyngas = 100 bar, [CO] : [H2] = 1, t = 22 h. a reaction mixture was partially lost during depressurization.

3.2.4 Substrate scope investigations for hydroformylation reactions

After the successful optimization and investigation of parameters for the hydroformylation reaction at 100 bar, reactions at lower pressures were conducted. Low pressures in an industrial process would lead to lower cost and a saving in synthesis gas, which can be somewhat expensive at higher purities. These conditions were used to investigate the substrate scope of this multiphasic reaction system, as it seems applicable to a wide range of substrates, as long as they are sufficiently non-polar.

3.2.4.1 Different chain length alkenes Different alkene chain lengths have been investigated at 40 bar. For shorter chains, faster reactions and higher selectivities are expected. The results are shown in Table 17.

Table 17. Multiphasic hydroformylation reactions with polymer particles Substrate X Schem. Sregio. l/b Ylin. ald. TOF (%) (%) (%) (%) (1/h) 1-Hexene 86 99 75 2.9 63 2413 1-Octene 47 98 73 2.7 33 945 1-Decene 32 95 72 2.6 22 548 Reaction conditions: [Rh(acac)(CO)2], TPPTS, [L] : [C] = 20, 150 mmol 1-octene, [S] : [C] = 40.000,

15 mmol n-dodecane as internal standard. VH2O = 20 ml, 25 mg/mlH2O PTA, T = 80°C, psyngas = 40 bar, [CO] : [H2] = 1, t = 22 h, stirring speed = 350 rpm.

As expected, the hydroformylation of shorter chain alkenes is quite successful at lower pressures, while it drops noticeably especially in conversion for longer chain alkenes. This makes these reactions at 40 bar challenging under the conditions used so far at 80 °C.

3.2.4.2 Substrate scope in homogeneous conditions To confirm the expected reactivities and for comparison with a homogeneous reaction system, reactions with different substrates have first been run in toluene with TPP as ligand (Table 18). Styrene is known to be very reactive in hydroformylation reactions, forming primarily the branched aldehyde. Cyclohexene was chosen to see the influence of the less reactive internal cis-configured double bond under these conditions. Limonene is a sample terpene with multiple possible double bonds and interesting as a natural substance. Eugenol was chosen as an

50 interesting natural substance that is also much more polar than the other substrates, giving information about the limitations of this process.

Table 18. Homogeneous hydroformylation reactions in toluene at 40 bar with different substrates Substrate [Rh]:[S] T X Schem. Sregio. l/b Ylin. ald. TOF (°C) (%) (%) (%) (b/l for a) (%) (1/h) Styrene 1 : 5000 80 > 99 > 99 85 5.8 a 85 a > 16222b Cyclohexene 1 : 5000 80 98 98 - - 95 724 1-Decene 1 : 5000 80 99 > 99 42 1.2 41 > 13712 b (R)-(+)-Limonene 1 : 5000 80 2 - - - - - (R)-(+)-Limonene 1 : 1000 100 94 96 > 99 - 90 142 Eugenol 1 : 1000 80 99 99 64 2.1 63 > 14152 b 1-Hexen 1 : 5000 80 > 99 > 99 74 2.8 73 > 25112 b 1-Octene 1 : 5000 80 99 99 99 2.8 45 > 17042 b Reaction conditions: 0.03 mmol [Rh(acac)(CO)2], TPP, [L] : [C] = 6, n(substrate) : n(standard) = 10 : 1. V푇표푙푢푒푛푒 = 20 ml, psyngas = 40 bar, [CO] : [H2] = 1, t = 22 h, stirring speed = 700 rpm. a For styrene there is a b/l ratio and selectivity to the branched aldehyde b The gas uptake of the reaction was faster than the gas delivery by the MFC, so the actual TOF could not be determined

The rate of most reactions under these conditions was indeed so fast that the MFC could not deliver the gas as fast as it was consumed, which made it not possible to determine the actual TOF at 10 % conversion. The chemoselectivity was also very high for almost all reactions and conditions, while the regioselectivity was the expected one for monodentate phosphine ligands. For cyclohexene the reaction rate was significantly lower, which is expected for internal double bonds. Limonene was not converted under these conditions and only gave good conversion and selectivity at a higher temperature and a higher catalyst to substrate ratio. That too is expected, as terminal alkenes where the β-position is tertiary are known to be even less reactive than internal double bonds if both carbon atoms are secondary.

3.2.4.3 Cyclohexene in multiphasic polymer particle systems The less reactive cyclohexene did not react under the mild conditions used before, as can be seen in Table 19. Harsher conditions were therefore applied.

Table 19. Multiphasic hydroformylation of cyclohexene with polymer particles Substrate Stirring rate T X Schem. Ylin. ald. TOF (rpm) (°C) (%) (%) (%) (1/h) Cyclohexene 700 80 4 74 3 - Cyclohexene 700 100 2 86 - - Cyclohexene 1500 100 30 97 29 70 Reaction conditions: [Rh]:[L]:[S] = 1:6:5000, n(substrate) : n(standard) = 10 : 1, 20 ml water, psyngas = 40 bar, [CO] : [H2] = 1, t = 22 h, [PP] = 25 mg/ml

Increasing the temperature from 80 to 100 °C was not sufficient. An increase in stirring rate from 700 to 1500 rpm at elevated temperature seemed to help reduce the mass transfer limitations. A yield of 29 % could be obtained under these conditions. It needs to be mentioned that a stirring rate of 1500 lead to a large Pickering emulsion phase (see Figure A11 in the appendix). This would not allow an easy product separation and catalyst recycling in a continuous process, as discussed earlier.

3.2.4.4 Styrene in multiphasic polymer particle systems Styrene is known to be a very reactive substrate for hydroformylation reactions but to lead to more branched than linear aldehydes. The reason for this is the +M-effect of the phenyl ring, increasing the electron density at the carbon atom next to the ring, which increases the chance of coordinating to the Rh-centre and therefor leading to branched aldehydes.

Table 20. Multiphasic hydroformylation of styrene with polymer particles Substrate [Rh]:[L]:[S] Stirring rate X Schem. Sregio. b/l Ylin. ald. TOF (rpm) (%) (%) (%) (%) (1/h) Styrene 1:6:5000 350 95 > 99 % 83 4.9 79 641 Styrene 1:6:5000 1050 97 > 99 % 85 5.5 82 1173 Styrene 1:20:40000 350 76 > 99 % 87 6.8 66 1881 Styrene 1:20:40000 700 78 > 99 % 87 6.6 67 2540 Styrene 1:20:40000 1050 82 > 99 % 86 6.2 70 2971 Reaction conditions: n(Rh) = 0.03 mmol, n(substrate) : n(standard) = 10 : 1, 20 ml water, psyngas = 40 bar, [CO] : [H2] = 1, t = 22 h, stirring speed = 700 rpm, [PP] = 25 mg/ml, 80°C

Styrene shows the expected high reaction rates and branched selectivity, which is why the regioselectivity in Table 20 is given in b/l instead of l/b. Even at low stirring rates of 350 rpm, the reaction leads to full conversion in the 22 h reaction time, although a higher stirring rate does

increase the TOF significantly, indicating mass transfer limitation. As can be seen in Figure A12 in the appendix, reactions with styrene lead to only Pickering emulsions, even without a visible aqueous phase after the reaction.

3.2.4.5 (R) - (+) - Limonene in multiphasic polymer particle systems Limonene is expected to be much less reactive than linear terminal alkenes, which has also been confirmed in earlier homogeneous reactions. Based on those results (Table 1) different starting conditions were chosen. The results are shown in Table 21.

Table 21. Multiphasic hydroformylation of (R) - (+) - Limonene with polymer particles Substrate [Rh]:[L]:[S] T Stirring rate X Schem. Sregio. Ylin. ald. TOF (°C) (rpm) (%) (%) (%) (%) (1/h) Limonene 1:6:3000 90 700 1 - - Limonene 1:6:3000 100 1500 1 - - Limonene 1:6:1000 100 700 28 96 59 16 12 Limonene 1:6:1000 100 1500 33 90 99 30 28 Reaction conditions: n(Rh) = 0.03 mmol, n(substrate) : n(standard) = 10 : 1, 20 ml Wasser, psyngas = 40 bar, [CO] : [H2] = 1, t = 22 h, [PP] = 25 mg/ml, 80°C. Non-linear aldehydes can also be internal ones, so no l/b ratio is given

Even at higher temperatures than with other substrates of 90 or 100 °C, no reaction could be observed at a Rh to substrate ratio of 1:3000. A decrease in the amount of substrate did lead to some conversion, but the resulting conditions of [R]:[S] = 1:1000 in combination with a high stirring rate led to an undesirable reaction system, see Figure A13 in the appendix. As has been found out earlier, the phase separation with these stirring rates is difficult to handle.

3.2.4.6 Eugenol in multiphasic polymer particle systems As could be shown in the homogeneous reactions, eugenol is very reactive. It is also more polar than the other investigated substrates. The starting conditions here were chosen at [Rh]:[L]:[S] = 1:20:40000. Under these conditions the reaction worked at decent conversion, see Table 22.

Table 22. Multiphasic hydroformylation of Eugenol Substrate Polymer particles X Schem. Sregio. l/b Ylin. ald. TOF mg/ml (%) (%) (%) (%) (1/h) Eugenol 25 61 74 64 1.8 29 2414 Eugenol 0 54 62 66 2.0 22 1123 Reaction conditions: n(Rh) = 0.03 mmol, [Rh]:[L]:[S] = 1:20:40000, n(substrate) : n(standard) = 10 : 1, 20 ml water, psyngas = 40 bar, [CO] : [H2] = 1, t = 22 h, stirring speed = 700 rpm, 80°C

The reaction however also worked well without particles. Furthermore, the separation was not satisfying, as the product of this reaction is just too polar. Eugenol therefore does not seem suited for a reaction system like this.

3.2.5 Phase separation strategies

Turning multiphasic reactions into a process requires product separation as well as the recycling of the catalyst and the polymer particles, so ideally the entire aqueous phase. The multiphasic hydroformylation reaction with polymer particles seems quite promising for some substrates in regard to the catalysis, but challenging in regard to the phase separation. The same can be said for reactions where high stirring rates are desired, even though it is known that the resulting Pickering emulsion can be huge in that case. One of the possible solutions to avoid the formation of these stable emulsions is the utilization of additives. Both salts and co-solvents have been investigated in an attempt to improve the phase separation. Another possible solution that was explored is to accept the formation of a PE, and to separate it after the reaction.

3.2.5.1 Effect of added salts on the phase separation It is known that the addition of salts facilitates the separation of aqueous phase and non-polar phase in the presence of phase transfer agents in the case of surfactants.[19] The mentioned reaction is also a hydroformylation of a long chain alkene with a Rh-TPPTS catalyst in a multiphase system with surfactants as phase transfer agents, so a comparison seems justified. The addition of different salts was therefore investigated, see Table 23. The main focus here was NaSO4, as the sulfate is similar to the sulfonate group on the TPPTS ligand, and is therefore

54 expected to be inert with respect to the catalyst. One neutral and one basic salt were then investigated as well.

Table 23 Influence of salts as additives on phase behaviour of multiphasic hydroformylation reactions with polymer particles as PTA Amount of salt in wt% of the total liquid phase 0.1 1 2 4 10 Phase behaviour change

NaSO4 No change more turbid agglomeration agglomeration - NaCl No change - - - agglomeration

NH4F - more turbid - - - Reaction conditions: n(Rh) = 0.03 mmol , [Rh]:[L]:[S] = 1:20:40000, n(1-octene) : n(dodecane) = 10 : 1, 20 ml water, psyngas = 40 bar, [CO] : [H2] = 1, t = 22 h, stirring speed = 700 rpm, 80°C

The low concentration of salt with 0.1 wt% led to no improvement in phase separation after the reaction. High concentrations of salt, 2 wt% and more, led to agglomeration of the particles, and a clear aqueous phase with only a few clumps in the most extreme case. The addition of salts for improved phase separation does therefore not seem to work for the polymer particle system, even though it does work for the similar micellar system.

3.2.5.2 Effect of co-solvents on the phase separation It was found that organic solvents can extract the product and lead to a better phase separation. For this reason the effect of different organic solvents on Pickering emulsions was investigated, see Figure A14 in the Appendix. Pure Pickering emulsions from reaction mixtures were mixed with different organic solvents. These emulsions do indeed separate when a co-solvent is added. Since the aqueous phase is expected to be on the bottom and also expected to be turbid, because of the particles, glycerol was discarded as an option. Methanol and 1,4-dioxane however seemed promising. These co-solvents where therefore added to hydroformylation reactions with particles, although in lower concentrations. 2 ml of polar, organic solvent were used to substitute 2 ml of water. The reason to keep the amount of co-solvent low is that a larger amount might change the system to drastically, and even turn it into a thermomorphic reaction system. The 1,4-dioxane addition was carried out in a reaction at 700 rpm, the results can be found in Table 24.

Table 24. Investigation of 1,4-dioxane on catalytic performance and phase separation Co-solvent X Schem. Sregio. l/b Ylin. ald. TOF (%) (%) (%) (%) (1/h) None 62 96 73 2.6 43 1170 Dioxane, 2 ml 87 61 72 2.5 38 1180 1:20:40000; 350 rpm, 18 ml H2O + 2 ml co-solvent; 500 mg PP

The phase separation did indeed improve a bit (see appendix Figure A15, but not significantly. The conversion increased noticeably with the addition of dioxane, but the chemoselectivity did drop as well, leading to a similar yield. The byproducts of the reaction were three times more hydrogenation products than isomerization products. The increased conversion could be explained by the high solubility of dioxane in both phases, and therefore a possible increase in mass transfer. Either way, the addition of 1,4-dioxane does not seem to be a good solution to the entwined problems of performance and separation.

The other co-solvent that seemed promising at separating Pickering emulsions or preventing their formation, methanol, was investigated at 350 rpm, based on the previous results. The catalytic performance and phase separation can be seen in Figure A16 in the appendix and Table 25.

Table 25. Investigation of methanol on catalytic performance and phase separation Co-solvent X Schem. Sregio. l/b Ylin. ald. TOF (%) (%) (%) (%) (1/h) None 43 98 73 2.7 30 770 Methanol, 2 ml 51 97 73 2.7 36 820 1:20:40000; 700 rpm, 18 ml H2O + 2 ml co-solvent; 500 mg PP

The polar solvent methanol did indeed improve the catalytic performance a little bit, but the separation was not improved but instead made worse. Both co-solvents do therefor not seem appropriate at preventing or destabilizing Pickering emulsions for the hydroformylation reaction.

3.2.5.3 Post reaction phase separation with organic solvents Two methods were utilized to be able to separate the polar and non-polar phases after the reaction, when facing Pickering emulsions. These separation methods are especially interesting 56 for substrates where even low stirring rates do not avoid the PE formation. The first method is the extraction of the product using a nonpolar or only slightly polar solvent like diethyl ether. This works fine and separates the nonpolar compounds from the aqueous catalyst phase. The product can then be separated from the low boiling ether. It also leaves an aqueous phase with particles and catalyst that can be recycled.[77]

The problem with the extraction method is that it is difficult to realize on a large scale, and that it requires large amounts of organic solvents. So while this method does work, an economically feasible, industrial process with it seems unlikely and would not meet the criteria for green chemistry.

3.2.5.4 Post reaction phase separation with centrifugation Pickering emulsions can be separated by centrifugation: This has been successfully applied and has been shown to work.[80] The PE mostly disappears when enough force is applied, however a tiny rest stayed under the conditions that were investigated, see Figure 26.

Figure 26. left: the pure PE used for the centrifugation experiment, mid: 10 min at 2000 rpm, right: 1 h at 3000 rpm

When using real reaction mixtures instead of pure PEs, the amount of residual PE was even less, when comparing it to the total volume, see Figure A17 in the appendix. The issue with centrifugation however is the difficulty to implement it in a large scale process, especially a continuous one. So while this does work, it seems impractical.

3.2.6 Catalyst recycling

Recycling of the aqueous phase, and therefore the catalyst, was done for multiple systems. Different situations are interesting for the particle approach. Being able to separate Pickering emulsions, being able to avoid them, and being able to ignore them.

3.2.6.1 Catalyst recycling with extraction Splitting up the Pickering emulsions that are formed during the reactions is not an easy task. Their high stability impedes the product separation and therefor the catalyst recycling. However, to prove the general recyclability of the polymer particle system, recycling experiments have been carried out. The product extraction was done using diethyl ether. As it was found that the product could be extracted with this nonpolar solvent, leaving the aqueous phase well separated, which enabled recycling of the catalyst the results are shown in table 26.

Table 26. Recycling experiments of the multiphasic hydroformylation of 1-octene using LX5 Run Conversion (%) Chemosel. (%) l : b TOF at 10% conv. (h-1) 1 75 >99 2.6 272 2 92 96 2.5 476 3 93 83 2.5 462 4 99 86 1.7 381 Reaction conditions: 0.03 mmol [Rh(acac)(CO)2], 0.18 mmol TPPTS, 150 mmol 1-octene, [C]:[L]:[S] = 1:6:5000, 15 mmol n-dodecane as standard. 0 500 mg of LX5, 20 ml H2O. 80 C, 700 rpm, 100 bar CO:H2 (1:1), 22 h

As can be seen in Table 26 and Figure 27, the recycling utilizing diethyl ether as an extraction solvent was successful. The selectivity decreased in multiple runs, which is however expected, since the reaction mixture was taken out of the reactor for the extraction and separation. This means that there was extensive contact to air. This likely led to some oxidation of the oxygen- labile phosphine ligand, decreasing the selectivity in the later runs. The loss in chemoselectivity was due to isomerization, with no detected hydrogenation products. A decrease in available ligands can also lead to an increased reaction rate at the cost of selectivity. This can explain the conversion going up after the first recycling. Leaching of Rh into the product phase in these experiments was investigated with ICP-MS. The loss of initial total Rh was 1.6 % for the first run

58 and 1.8 % on the fourth run, which is more percentwise than in similar reactions. However when put in perspective and given in absolute amount of Rh loss, the leaching is actually quite low with 0.2 ppm of Rh in the product phase. This is because only very low amounts of initial metal are required for the reaction.

100 90 80 70 60 50 40 30 Run1 Run2 20 Run3

Conversion to aldehydes (%) Run4 10 0 0 5 10 15 20 Time (h) Figure 27. Conversion to aldehydes vs. time in the recycling experiments of 1-octene using polymer particles as PTA. For conditions see Table 26[80]

An optimized extraction could probably avoid air contact, keeping the catalyst selective for more runs. This would not change the fact that the catalyst recycling cannot be achieved by simple decantation. Using large amounts of organic solvents makes this supposedly green process much less economical and environmentally friendly.

3.2.6.2 Optimized recycling experiments with polymer particles After the promising results with the cheap and readily available TPPTS and the more selective but also more expensive Danphos ligand, recycling experiments were conducted, see Table 27. The separation of the reaction mixtures were satisfactory. However, for an easier decantation of the non-polar substrate/product phase after taking the mixture out of the reactor, a centrifugation at 3000 rpm at 15 min was performed.

Table 27. Recycling experiments of the multiphasic hydroformylation of 1-octene Conversion Chemosel. Run Ligand l : b TOF at 10% conv. (h-1) (%) (%) 1 73 97 2.5 1600 2 74 95 2.4 1700 TPPTS 3 67 93 2.4 1384 4 74 88 2.3 1400 1 56 98 2.9 1640 2 50 97 2.8 1532 Danphos 3 44 96 2.7 1104 4 44 91 2.4 988 Reaction conditions: 0.00375 mmol [Rh(acac)(CO)2], 0.075 mmol ligand, 150 mmol 1- octene, [Rh]:[L]:[S] = 1:20:40000, 15 mmol n-dodecane as standard, 700 mg of PTA, 20 ml H2O, 80°C, 350 rpm, 100 bar CO:H2 (1:1), 22 h

The recycling experiments with the TPPTS ligand were successful, with the yield only dropping by 5 % from the first to the fourth run. The selectivity dropped a bit with each run, which can easily be explained by the expected oxidation of some of the phosphine ligands over time. This is due to the reaction mixture beeing taken out of the reactor between each run under non inert conditions. The loss of Rh in these reactions was very similar to the recycling runs with TPPTS as a ligand. The Rh leaching was 1.4 %, or 0.2 ppm in the product phase after the first reaction. Again, a seemingly high percentwise loss, but a low amount of Rh in the product phase. This is due to the very low amount of total Rh used as a catalyst. The conditions used for these recycling experiments are quite promising. The only aspect that might need some improvement is the phase separation. A simple solution could be a decantation directly in the reactor, as taking the mixture out of the reactor always made the phase separation worse. This would make the centrifugation step obsolete and could allow a continuous process e.g. utilizing a decanter and then avoiding oxidation of the ligands. As described later, it is also possible to just recycle the small amount of residual Pickering emulsions, as they do not accumulate after multiple recycling runs. The TON after the four runs was 115000 for TPPTS and 77000 for Danphos, making the process very promising.

3.2.6.3 Recycling of the aqueous phase including the Pickering emulsion Since it was shown that the amount of PE was low when using low stirring rates, it was investigated if it is possible to simply recycle the PE together with the aqueous phase. This allows a simple decantation of the product phase. This was done in recycling experiments, where it could be shown that the PE does not significantly accumulate even after three recycling runs. The removal of the nonpolar phase in this case was done manually with a pipette, where larger droplets were thoroughly removed by piercing them in the first recycling series. This led to increased air contact as it took around 15 minutes to minimize the macro emulsion. Note that only macroscopic, non-stable emulsions can be removed like this, while PEs are too stable to be destroyed by poking them with a pipette. A second recycling series was done, where the focus of the removal of the oil phase was minimizing the separation time, so the removal of macro emulsions was less thorough. The amount of PE after each recycling is shown in Table 28.

Table 28. Recycling experiments for the multiphasic hydroformylation of 1-octene. The macro emulsion was manually destroyed; the PE was recycled with the aqueous phase. Initial reaction 1. recycling 2. recycling 3. recycling a) Amount 2.5 2.5 2.8 2.8 b) of PE (ml) 2.8 3.6 3.4 - Reaction conditions can be found in Table 29 a) careful separation of the macro-emulsion, ca. 15 min b) quick separation of the macro-emulsion, ca. 2 min

As can be seen, the amount of Pickering emulsion did not significantly increase when recycling the aqueous phase together with the formed Pickering emulsion. There was almost no accumulation, which indicates that the PE and the other phases are in equilibrium under reaction conditions. This means that a continuous or batch-wise recycling process does absolutely seem possible. The catalytic performance can be found in Table 29. The reactions were performed at 20 bar, as the catalytic results were not the focus of the experiments.

Table 29. Recycling experiments for the multiphasic hydroformylation of 1-octene with recycling of the Pickering emulsion Conversion Chemosel. Run Method l : b (%) (%) 1 36 26 2.9 2 33 20 3.2 Careful PE-removal 3 34 20 3.1 4 37 20 3.1 1 23 20 3.0 2 26 18 2.6 Quick PE-removal 3 20 19 2.4 4 - - - Reaction conditions: 0.03 mmol [Rh(acac)(CO)2], 0.18 mmol ligand, 150 mmol 1-octene, [Rh]:[L]:[S] = 1:6:5000, 15 mmol n-dodecane as standard, 500 mg of PTA, 20 ml H2O, 80°C, 350 rpm, 20 bar CO:H2 (1:1), 22 h

The results are as expected for reactions at 20 bar, with low conversion and chemoselectivity. The side products were almost exclusively isomerized alkenes and below 1 % hydrogenation products. The recycling was also quite successful in the sense of retained yields.

3.2.7 Suzuki-Miyaura reactions with polymer particles in a multiphasic liquid-liquid system

The multiphasic reaction system applied in the hydroformylation reactions is not necessarily limited to this specific reaction. Since the polymer particle system is working well with the hydroformylation reaction, other reactions were investigated to see if the particle system is versatile. The goal here was to keep the main setup the same, meaning an aqueous phase with water soluble ligands, and non-polar products that can be separated. This should bring the same benefits of a simple catalyst recycling via decantation of the product phase.

The Suzuki-Miyaura reaction is a catalytic C-C-coupling reaction that plays an important role in organic chemistry.[86,87] This Pd-catalyzed reaction is typically used for the coupling of an aromatic halide and an aryl boronic acid. When using simple substrates without much functionalization, except for one methyl group to be able to detect homo-coupling, the product

62 is very non-polar. The reaction scheme is shown in Figure 28. In a setup like this the product separation is expected to be simple.

Figure 28. Example for a Suzuki-Miyaura reaction.

A few facts were found out when working on this system:

- Inorganic bases are commonly used for the reaction, but early investigations showed that the particles do clump up when in the presence of inorganic bases. This is in agreement with the results from the experiments, where salts were added to improve phase separation. The organic base triethylamine was therefore chosen to replace them. - The selectivity of the reactions varied only by a few percent and was always above 95 %. The results are only given in yields for this reason. - The Pd-TPPTS stock solution oxidized quickly, so fresh stock solutions were prepared frequently. To avoid wasting Pd, the amounts weighed in were quite low, resulting in an error of a few percent.

To check the general viability, very reactive substrates were chosen as a starting point. A multiphasic reaction with iodo-benzene did work well in terms of catalytic performance, as can be seen in Figure 29.

Figure 29. Multiphasic Suzuki-Miyaura reaction with polymer particles. Triethylamine 8.7 mmol; Pd(OAc)2 0.025 mmol; TPPTS 0.12 mmol; Me-Ph-B(OH)2 4.8 mmol; 4-Br-Ph 4 mmol; M:L:Substrate:Substrate(Ph-I) = 1:4.8:160:192; dodecane (standard) 0.47 mmol; 10 ml water; 60°C; 900 rpm; 100 mg polymer particles; 240 min

The issue for this reaction was the phase separation after the reaction, see Figure A18 in the appendix. Instead of a clear non-polar phase and an aqueous phase that would have enabled easy separation, only one big PE was formed. This is without mechanical stirring and with the milder stirring of a magnetic stirring bar. The reduction in stirring speed that was found to be effective in earlier hydroformylation reactions was therefore not practical. For this reason co- solvents were tested and t-amylalcohol was found to be effective at leading to a clear two phase system. So unlike in the pressurized hydroformylation system, co-solvents were helpful in this case. They were, however, not fully sufficient, as additional solvent was needed after the reaction to achieve complete phase separation. For the reaction, 5 ml t-amylalcohol were added with an additional 15 ml after the reaction, to fully separate the mixture.

Figure 30. Multiphasic Suzuki-Miyaura reaction with polymer particles and t-amylalcohol for a better phase separation. t-amylalcohol 5 ml; triethylamine 8.7 mmol; Pd(OAc)2 0.004 mmol; TPPTS 0.02 mmol; Ph- B(OH)2 4.8 mmol; 4-Br-toluene 4 mmol; M:L:Substrate:Substrate = 1:5:1000:1200; dodecane (standard) 0.47 mmol; 10 ml water; 60°C; 900 rpm; 100 mg polymer particles; 240 min

As can be seen in Figure A19 (appendix) the reaction mixture did separate well, leading to a system that promises easy catalyst recycling. The Pd leaching, determined by ICP-OES was 2 %, showing that most of the catalyst stays in the aqueous phase, as intended. To check for the influence of the polymer particles, a reaction analogous to the previous one (Figure 30) was conducted but without polymer particles, see below in Figure 31.

Figure 31. Multiphasic Suzuki-Miyaura reaction without polymer particles and with t-amylalcohol for a better phase separation. t-amylalcohol 5 ml; triethylamine 8.7 mmol; Pd(OAc)2 0.004 mmol; TPPTS 0.02 mmol; Ph- B(OH)2 4.8 mmol; 4-Br-toluene 4 mmol; M:L:Substrate:Substrate = 1:5:1000:1200; dodecane (standard) 0.47 mmol; 10 ml water; 60°C; 900 rpm; 240 min

The reaction does indeed benefit a lot from the polymer particles, as the reaction only yields 20 % after four hours in this setup, with the amylalcohol probably acting as a weak phase transfer agent, leading to some reaction. Recycling reactions with the particle system were attempted, but the reaction lead to Pd-black formation, even when increasing the Pd:L ratio from 1:10 to 1:15. The recycling runs never gave more than 10 % yield, and while a Pd:L ratio of 1:20 stabilized the Pd, the reaction did not work anymore at this high ligand concentration. To conclude, the Suzuki-Miyaura can be carried out in a multiphasic polymer particle system with easy product separation, when using a co-solvent. The attempt to recycle the catalyst however, was not successful, due to the formation of Pd-black, which is a very common problem when working with Pd catalysts. The general principle of utilizing the polymer particles for different reactions and employing one of the developed methods to achieve product separation from the catalyst phase does seem to work well though.

3.2.8 Role of the polymer particles in the multiphasic hydroformylation reactions

In previous work the particles have been assumed to act as microreactors, solubilizing substrate while being suspended in the aqueous phase. Since the reaction system in multiphase systems seems to easily form Pickering emulsions, this suggests that it is energetically favorable for the polymer particles to be at the interface of polar and non-polar phases.

Figure 32. Polymer particles can be viewed as microreactors (left) or as catalyst carriers that bring the catalyst to the interface (right)[80]

Since it could be shown that the particles are efficient catalyst carriers for anionic ligands, it could be an important feature of the particles to lead to a locally high catalyst concentration in the interface between the aqueous phase and the substrate droplets. Therefore, mass transfer limitations are reduced, as the catalyst is brought in close proximity of the substrate (Figure 32). Under catalytic conditions, both, carrying the catalyst to the interface and acting as a microreactor might be relevant, but the catalyst carrying aspect would be the dominant effect based on these results.

3.3 Multiphasic, catalytic hydroformylation reactions without phase transfer agents

In the preceding chapters the ability to act as phase transfer agents was shown for the polymer particles. This is likely due to an accumulation of the particles at the interface, carrying the catalyst there, close to the substrate phase. However as shown before, the reaction does indeed also take place without PTAs under some conditions. To the best of the authors knowledge, this was only mentioned in four publications before.[52–55] It seems counter intuitive, as the catalyst is expected to be a water soluble Rh-TPPTS catalyst and therefor in the aqueous phase, while the solubility of long chain olefins is very low in water. Likely a different mechanism makes it possible however to achieve full conversion, even without PTAs. For the literature regarding this topic, it should be mentioned that some of the best results were obtained in a jet-loop reactor, which creates very high interface areas. The one reaction presented in this work so far is shown again in Table 30.

Table 30. Multiphasic hydroformylation reaction without any phase transfer agent, conditions see Table 15 (Particle concentration variation) PTA X Schem. Sregio. l/b Ylin. ald. TOF (10 % X) (mg/ml) (%) (%) (%) (%) (1/h) 0 99 90 61 1.5 54 4364

As can be seen, full conversion can be achieved over 22 h. The selectivity is notably lower than with polymer particles as phase transfer agents, but it still leads to a yield of around 50 %. It seems that this approach is better suited when wanting to avoid additional substances in the system, while the use of polymer particles allows for higher selectivities. Recycling is another point that comes to mind, on one hand, having no PTAs does lead to very good phase separation, on the other hand, the catalyst carrier properties of the particles might reduce Rh and P leaching. To investigate the system more, different reactions without PTAs have been carried out.

3.3.1 Ligand influence

Since it is not obvious how the reaction works under these conditions, the influence of the ligand concentration and ligand type was investigated. The results are shown in Table 31. Byproducts were almost exclusively isomerization products.

Table 31. Multiphasic hydroformylation reactions without polymer particles as phase transfer agents Entry [Rh]:[P]:[S] c(ligand) in the Conv. Chemosel. Regiosel. Yield TOF l/b aq. phase (%) (%) (%) (%) (1/h) (mmol/l) 1 96 81 66 52 4040 1.9 1:20:80000 1.9, TPPTS 2 32 81 68 18 54 2.1 1:6:5000 9, TPPTS 3 <5 - - <2 - - 1:50:80000 4.7, TPPTS 4 <1 - - - - - 1:10:80000 1, sulfoxantphos Reaction conditions: 700 rpm, 100 bar of syngas CO/H2 = 1/1, 150 mmol 1-octene, 80°C, 20 ml water

As seen in Table 31, the yield drops significantly from around 50 % (entry 1) to 20 % (entry 2) when using more Rh but also more phosphine ligand with a minimal gain in regioselectivity. When using the same conditions as in entry 1, but much more ligand (entry 3) at a high P : Rh ratio of 50, the conversion drops further. Using the same conditions as in entry 1 and keeping the P : Rh ratio the same but using the bidentate ligand sulfoxantphos (SX), the yield drops below the detection limit. This leads to interesting insights. The bidentate ligand binds much stronger to the Rh center compared to a monodentate ligand, reducing the probability to generate unmodified Rh-carbonyl species in the course of the reaction. It is known that the SX- ligand is water soluble and would not be expected to enter the non-polar phase. This and the typically lower rate of SX compared to TPPTS lead to no detectable aldehyde formation. A high concentration of ligand of 9 mmol/l and a high ligand to Rh ratio of 50, both decrease the yield drastically. In both cases the catalyst is more likely to be coordinated by multiple phosphine ligands.

3.3.2 Proposed mechanism of the multiphasic reaction without phase transfer agents

It seems that a decrease in water soluble ligand increases the observable reaction rate. This leads to the conclusion that at least some Rh species without any phosphine ligand is formed, since the Rh species are in equilibrium, as shown in Figure 33.

Figure 33. Equilibria of different Rh species in the presence of TPPTS, CO and H2 as possible ligands. From these catalyst complexes all are polar and water soluble, except HRh(CO)4.

A Rh catalyst without any phosphine ligand would be highly active but very unselective, leading to a l/b ratio of around 1.4 – 1.6. This cannot be the only explanation for the results shown in Table 31 however, as the l/b ratio is a bit higher than that. Another explanation is that low P- coordinated Rh species are formed. These complexes, which are known to be surface active, would accumulate at the interface of the aqueous and the substrate phase. This would lead to a higher l/b ratio of ca. 2.4 though and the reaction rate is quite high for this effect, especially considering the moderate stirring rate of 700 rpm. The explanation of the observed results might therefore be a mix of those two phenomena, see Figure 34, leading to a mix of selective and unselective hydroformylation. 69

Figure 34. A low concentration of ligand leads to the formation of low coordinated or even unmodified Rh-carbonyl species, which are either soluble in the substrate phase or accumulate at the interface.

3.3.3 Influence of pressure on particle-free multiphase reactions

Since the state of the equilibrium of Rh species is suspected to be very relevant for the multiphasic hydroformylation without phase transfer agents, the factors that shift it have been investigated. Apart from the phosphine concentration, the CO concentration is also very relevant. To change the CO concentration in solution, the syngas pressure has been changed. The results are shown in Table 32 and Figure 35.

Table 32. Pressure variation in multiphasic hydroformylation reactions without PTA P (bar) Conv. (%) Chemo.(%) l/b Y 20 34 26 2.9 7 40 50 52 2.8 19 60 47 66 2.4 22 80 75 76 2.2 39 100 96 81 1.9 54 150 mmol 1-octene, 15 mmol n-dodecane as internal standard, [S]:[L]:[Rh] = 80000:20:1, 20 ml H2O, 80°C, 700 rpm, CO:H2 (1:1), 22 h.

As can be seen in Table 32 and Figure 35 the yield of aldehydes drops dramatically at a pressure of 20 bar, and therefore at low CO concentration. The assumption that the equilibrium is being shifted towards Rh species with one or more phosphine ligands fits the observation since the l/b ratio goes up with a decrease in syngas pressure. The byproducts were isomerization products with ca. 0.5 percent points (p.p.) of hydrogenation products.

100

100 bar 80 80 bar

60 60 bar 40 bar 40 20 bar

Y(aldehydes) % in Y(aldehydes) 20

0 0 5 10 15 t in h 20 25 Figure 35. Yield of aldehydes over time for pressure variation in multiphasic hydroformylation reactions without PTA

While these results at a stirring rate of 700 rpm are interesting, the reactions have been repeated under slightly different conditions but especially with a higher stirring rate. This could lead to more Rh-phosphine catalyst at the increased interface. Those reactions at 1750 rpm are shown in Table 33.

Table 33. Pressure variation in multiphasic hydroformylation reactions without PTA at a high stirring rate of 1750 rpm Pressure bar X Schem. Sregio. l/b Ylin. ald. % % % % 20 13 32 76 3.1 4 40 54 52 73 2.7 22 60 84 67 69 2.2 39 80 99 99 58 1.4 50 100 99 90 61 1.5 54 120 98 91 59 1.4 52 Reaction conditions: 1750 rpm, [Rh]:[L]:[Substrate] = 1:20:40000, 150 mmol 1-octene, 15 mmol n-dodecane as internal standard, 20 ml H2O, 80°C, CO:H2 (1:1), 22 h.

The reactions at higher stirring rates are shown in Table 33 and show similar results. Higher yields at 40-80 bar can be observed, but the difference is not major. The yield towards aldehydes can be found in Figure 36. The byproducts were mainly isomerization products with less than 1 p.p. of hydrogenation products at pressures of 40 bar and higher. At 20 bar however, ca. three times more hydrogenation product were formed than isomerization products.

100 20 bar 90 40 bar 80 60 bar 70 80 bar 60 100 bar 50 120 bar 40 30

20 Yield to aldehydes (%) aldehydes to Yield 10 0 0 5 10 time (h) 15 20 25 Figure 36. Yield of aldehydes over time for high stirring rates in multiphasic hydroformylation reactions without PTA, conditions see Table 33

3.3.4 Influence of stirring rate on particle-free multiphase reactions

Mass transfer limitation is a common problem in multiphasic reactions. Even when using polymer particles as mass transfer agents, limitations can be an issue for most catalyst concentrations and stirring rates. On the one hand, the absence of phase transfer agents would be expected to increase the problem. On the other hand, the formation of a catalyst that is soluble in the substrate phase would decrease the mass transfer limitation, although it would also decrease selectivity. The formation of this non-polar catalyst however would probably also depend on mass transfer, specifically on the transfer of CO into the aqueous phase and of Rh species between the polar and non-polar phase. It should be noted that the gas dispersion

stirrer increases the input of gases a lot when going from 700 to > 1000 rpm. The results of the stirring experiments can be seen in Table 34 and Figure 37.

Table 34. Stirring rate variation in multiphasic hydroformylation reactions without PTA Stirring Rate Conv. Chemosel. Regiosel. l/b Yield TOF ( 10 % Yald) (rpm) (%) (%) (%) (%) (1/h) 350 43 80 66 1.9 23 1108 700 64 81 67 2.0 35 1715 1050 98 84 63 1.7 52 2532 1400 87 83 66 1.9 48 2640 1750 99 90 61 1.5 54 4444 Reaction conditions: [Rh]:[L]:[Substrate] = 1:20:40000, 150 mmol 1-octene, 15 mmol n-dodecane as internal standard, 20 ml H2O, 80°C, 100 bar CO:H2 (1:1), 22 h, 100 bar CO:H2 (1:1)

As can be seen, the multiphasic reaction without phase transfer agents is strongly dependent on the stirring rate. At 350 and 700 rpm the selectivity is the same, while the conversion goes up from roughly 40 to 65 %. This is an indicator for mass transfer limitation, although it is not easy to clearly pin down a specific reason for that. The increased interface between the two liquid phases seems to have the biggest impact though, because the selectivity stays the same. With stirring rates of up to 1400 rpm, hydrogenation products were formed in relevant amounts, up to 10 p.p. At 1750 rpm, hydrogenation byproducts went down to below 1 p.p.

100 1750 rpm 90 1400 rpm 80 1000 rpm 70 700 rpm 60 50 350 rpm 40 30

Yield to aldehydes (%) aldehydes to Yield 20 10 0 0 5 10 Time (%) 15 20 25 Figure 37. Yield of aldehydes over time for stirring rate variation in multiphasic hydroformylation reactions without PTA, conditions see Table 34.

When going from 700 to 1000 rpm or more, there is a bigger difference. Considering a margin of error of a few percent points, there is still a general drop in regioselectivity. A possible explanation for this would be an increased CO input leading to an increased CO concentration in solution, especially the aqueous phase, and thus shifting the equilibrium to the unselective Rh carbonyl species. The chemoselectivity does go up with higher stirring rates. This can be explained by the faster and a bit less regioselective reaction, which consumes the substrate much faster and therefore leaves less time for the substrate to isomerize or get hydrogenated.

3.3.5 Influence of preformation conditions and aqueous volume on selectivity and conversion

Since the state of the Rh-catalyst seems very influential on this system, the influence of the ligand concentration in combination with the aqueous phase was investigated. In the same series of experiments, the preformation time was investigated. For these experiments, the metal to phosphine ligand ratio was set to L/Rh = 30. The aqueous phase was then reduced from 20 to 15 and then 10 ml. Even though the amount of ligand and Rh was kept the same, the reduced amount of aqueous phase does lead to a higher absolute concentration of phosphine ligand in the catalyst phase. The results can be seen in Table 35.

Tabel 35. Influence of different amounts of aqueous volumes at a preformation time of ca. 90 min Aqueous X in % Schemo in % Sregio in % l/b ratio Y in % volume 20 ml 77 84 66 1.9 43 15 ml 98 88 65 1.8 57 10 ml 98 97 63 1.8 60 Reaction conditions: [Rh]:[TPPTS]:[Substrate] = 1:30:40000, 150 mmol 1-octene, 15 mmol n-dodecane as internal standard, 80°C, 100 bar CO:H2 (1:1), 1750 rpm, 22 h

The side products were almost exclusively isomerization products. These results show that a reduced amount of aqueous phase with a set amount of catalyst leads to increased conversion while also decreasing the regioselectivity. This is indeed counter intuitive, as a higher concentration of TPPTS would be expected to lead to catalyst species which have a higher number of coordinated phosphine ligands, leading to less conversion but more linear aldehydes.

It should be mentioned though that the decrease in regioselectivity is not that pronounced. A possible explanation of this effect is the increased interface area between non-polar and polar phase because of smaller droplet sizes in the case of less aqueous phase. This could increase the mass transfer. The CO transfer into the aqueous phase would have an influence on the catalyst equilibrium described in Figure 33. A parameter of vital importance for this system is also the catalyst leaching. A catalyst without any phosphine ligands could lead to a loss of Rh into the product phase. The Rh leaching was checked for the volume of 15 and 10 ml aqueous phase. For 15 ml the loss of initial Rh was below the detection limit of 0.2 % of the initial amount, or below 0.05 ppm in the product phase. For 10 ml the Rh leaching was significant. The reaction was performed twice and the average Rh loss was 10 %, or 1.7 ppm in the product phase. For these reasons the following reactions were performed with 15 ml of aqueous phase.

Another investigated parameter was the preformation time. For hydroformylation reactions the preformation exists to form the Rh[(H)(CO)2(TPPTS)2] from the Rh[(acac)(CO)2] precursor or from the solubilized Rh[(TPPTS)4]. The resulting complex is in equilibrium with the active

Rh[(H)(CO)(TPPTS)2] species. Because the reactions were conducted with a catalyst stock solution, the initial Rh species was indeed one with four phosphine ligands. The results of these experiments are shown in Table 36.

Tabel 36. Influence of preformation times with 15 ml of aqueous phase Preformation X in % Schemo in % Sregio in % l/b ratio Y in % time 35 min 99 84 58 1.4 48 55 min 99 89 58 1.4 51 95 min 98 88 65 1.8 56 Reaction conditions: [Rh]:[TPPTS]:[Substrate] = 1:30:40000, 150 mmol 1-octene, 15 mmol n-dodecane as internal standard, 15 ml H2O, 80°C, 100 bar CO:H2 (1:1), 1750 rpm, 22 h

Again, side products were almost exclusively isomerization products. When varying the preformation time, there seems to be an influence when going from ca. 30 min of preformation time to ca. 95 min. Interestingly the chemoselectivity and regioselectivity increase by a few percent when applying longer preformation times. These results are not expected, as the starting point is the catalyst species with only phosphine ligands, where unselective carbonyl

75 species only form over time. For an explanation of this effect further experiments would have to be conducted. The Rh loss was investigated for the reactions with 55 and 95 min preformation time and were both times found to be below the detection limit of 0.05 ppm, or 0.2 % of the initial amount of Rh.

3.4 Development for key experiments for multiphasic reaction systems

This work has been done in collaboration with the Sonderforschungsbereich (SFB) / Transregio 63. The SFB is a research collaboration, mainly based in Germany and investigates new solutions for catalytic, industrial processes. The approaches that are examined are multiphasic reaction systems using different liquid phases and a molecular catalysts. The liquid phase in some of the systems is monophasic during the reaction and is switched for the separation step. An easy product separation with efficient catalyst recycling is the overall goal. One investigated system was the thermomorphic reaction setup, which uses a mixture of solvents and substrate, forming a single phase under reaction conditions. The phase can be separated when cooled down, where product and catalyst are in two different phases. This allows product separation and catalyst recycling after the reaction. The other main investigated reaction type is the micellar reaction system. In that case, a surfactant is added to a nonpolar substrate phase and an aqueous catalyst phase. This means the micellar catalysis is quite similar to the multiphasic catalysis with polymer particles, another system that has been investigated in the SFB/Transregio 63. Part of this work was the development of a few key experiments to determine the viability of these multiphasic reaction systems for a given reaction. The idea is to find a set of simple experiments that give insight into whether or not a reaction can be performed in a given multiphasic reaction system. For example, can a C-C-coupling reaction, be efficiently performed in a multiphasic micellar or polymer particle system. To confirm this, a couple of reactions with available data for micellar reaction systems from literature were chosen, so that key experiments can be evaluated for their accuracy in predicting the reaction system to be viable or not for a given reaction. For that reason the focus was put on the micellar setup, as there is much more literature available in this field.

3.4.1 Determining the feasibility of micellar and of polymer particle multiphase systems for different reactions

Developing key experiments is not the only relevant aspect of determining the viability of a new multiphasic approach for a reaction. Before starting reactions, a few assessments have to be

77 done, as some reactions are not compatible with an inherent property of a certain system. The path to arrive to a process with a multiphasic system is shown in Figure 38. It must be noted that the last part, optimization, is not the focus of this work, as it is quite time consuming. The point is to quickly gain information for a given reaction, if a further optimization does look promising.

Figure 38. Three simplified steps of bringing a certain reaction to a process using a multiphasic reaction system.

This means that a range of reactions can be excluded for some reaction setups, unless the reaction system is modified. For example, the micellar and polymer particle systems usually use water as the polar phase. This means that any reaction, where substrate, product or catalyst, are not stable in the presence of water, is not suitable. Of course most of these incompatibilities can be worked around if larger modifications are made to the system. For example, a possible solution for a water labile substance would be using a dry, aprotic, polar solvent instead of water. The key experiments, however, do not focus on modifying the reaction system to match reactions that are not compatible, as the goal is to keep them as simple as possible. The advantage of a simple system is the ease of use. So a company or research group can quickly get

78 an idea of whether or not one of these multiphasic systems is feasible for a given reaction. Hopefully leading to a process where a selective catalyst can be recycled efficiently while the product can easily be separated.

3.4.2 Theoretical assessment of reaction compatibility

For the micellar reaction systems and the polymer particle system, the requirements for compatibility with a given reaction include multiple points and are summarized in Table 36. Note that it is possible to find workarounds for all of these problems. All of the solutions however alter the system in a relevant way, removing the simplicity of the key experiments. The requirements and possible solutions are presented in Table 36.

Table 36. Requirements for a reaction to be compatible with an unmodified particle or micellar setup and possible solutions. Entry Requirements for key experiments Possible solutions (would require alterations of the system) 1 Reactants, catalyst and product Use of a polar, aprotic solvent instead of water need to be stable in the presence of water 2 All components need to be stable Different polymer particles can be synthesized. in the presence of polymer (the use of some different surfactants is particles / surfactants included in this work, changing them is easier) 3 Catalyst needs to be water soluble Commercially available non-polar ligands can be sulfonated, making them polar 4 Product needs to be in a non-polar When having polar products, a non-polar phase after the reaction (possibly catalyst can be used. This reverses the after cooling) polarities and therefore enables the separation of product and catalyst 5 Catalyst needs to have a low Co-solvents can be used, changing the solubility in the product phase partitioning coefficient of the catalyst

These solutions are, for the most part, not considered in this work however, as the goal is a simple check for standardized conditions, which don’t require modifications of the reaction system. Only the simplest ones are being implemented, three different surfactants are tested, giving an overview over a broad class of surfactants, as well as the use of a co-solvent in the case of a working surfactant system to gain information about the phase behavior.

3.4.3 Chosen reactions for investigation with key experiments

Using the criteria mentioned before, a set of reactions was chosen to check the key experiments. If possible, reactions were chosen, where data from literature is available, that allow to confirm the key experiments. C-C-coupling reactions with simple substrates seem to be a good starting point, so the Mizoroki-Heck reaction was chosen. It is similar to the Suzuki- Miyaura reaction, which was also carried out in this work, but with polymer particles. Both reaction schemes are shown in Scheme 4 and 5.

Scheme 4. Suzuki-Miyaura coupling reaction, X is typically I or Br

Both reactions usually use aryl halides and aryl boronic acid or vinyl arenes, respectively, as substrates. Variations in substrates as well as in functional groups are known, however.[88]

Scheme 5. Mizoroki-Heck coupling reaction, X is typically I or Br

As can be seen, the products in these examples are non-polar. In the presence of an aqueous phase, they are therefore expected to form their own phase, enabling product separation and catalyst recycling. After all, this is the goal when using multiphasic, micellar or polymer particle systems. The other reaction of choice to investigate was the hydroformylation of 1-octene.

3.4.4 Conditions chosen for the key experiments

A fixed set of parameters was chosen: generally 30 ml of water, 0.03 mmol metal, 0.18 mmol ligand and 15 mmol substrate with 27 ml of inert co-solvent in one following reaction were used. In addition, one of three surfactants was used, either 1 wt% of SDS or CTAB, or 8 wt% of Marlipal 24/70. The different amount of surfactant is due to non-ionic surfactants being generally weaker. Temperature, pressure (in case of gaseous substrates), possible additives and so on are taken from homogeneous reactions from literature. These conditions can of course be modified if it makes sense for a certain reaction, but serve as a starting point.

As mentioned before, the focus will be put on multiphasic reaction systems using surfactants, instead of polymer particles as phase transfer agents. The basic conditions are always kept the same, if possible. With surfactants, three different ones are being tested as it has been shown that the class of surfactant, cationic, anionic or nonionic, can have a big influence on catalysis or phase separation. Three reactions are therefore run using one surfactant of each of these classes, CTAB, SDS and Marlipal 24/70. These three experiments give insight on the feasibility of a micellar catalytic reaction system. Should one or more of these reactions yield reasonable success, e.g. more than 7 % of the desired product, then one further experiment with a co-solvent is carried out. In this fourth and final experiment, a volume ratio of roughly 1/1 of nonpolar and polar phase is chosen. The goal of this experiment is to gain insight on the phase separation of the reaction mixture after the reaction. Catalyst leaching and simplicity of product separation can be investigated with this approach. Instead of using large volumes of co-solvent, the amount of product can also be increased. The procedure with the three or four key experiments is shown in Figure 39.

Figure 39. Pathway for the key experiments (purple boxes) and their conditions (green boxes)

3.4.5 Key experiments and the comparison with optimized reactions

Hydroformylation reactions were carried out, taking the previously mentioned reaction conditions as a starting point. The catalyst of choice was a Rh-Sulfoxantphos catalyst, reported

[20] in literature, with 0.03 mmol of Rh[(acac)(CO)2] precursor and 0.12 mmol of Sulfoxantphos ligand. 1-Octene was chosen as the substrate. The reaction was performed with CTAB, SDS and Marlipal 25/70, see Table 37.

Tabel 37. Key experiments for a hydroformylation reaction in multiphasic liquid/liquid systems with surfactants

Preformation time X in % Schemo in % Sregio in % l/b ratio Y in % CTAB 93 72 >99 >100 66 SDS 25 73 97 33 18 Marlipal 24/70 60 55 99 64 33 CTAB + co-solventa 25 58 >99 >100 16 Reaction conditions: [Rh]:[Xantphos]:[1-Octene] = 1:4:500, 15 mmol 1-octene, 15 ml H2O, 95 °C, 40 bar CO:H2 (1:1), 700 rpm, 4 h a 27 ml of toluene were used as a co-solvent

As can be seen, the results are respectable, which is in agreement with the literature results.[20] The yield was generally high enough to qualify as a promising approach, with the chemoselectivity being the least satisfactory parameter. The side products were almost exclusively isomerization products. Based on the initial three reactions, CTAB was chosen as the surfactant of choice for the following reaction with a co-solvent. Toluene was chosen there, but unfortunately it did not only make the catalytic performance worse, but also did not lead to a good phase separation. The phase behavior of the reaction with CTAB, both with and without a co-solvent can be found in the appendix (Figure A20 and A21).

Another investigated reaction was the Mizoroki-Heck reaction. Here, a Pd-TPPTS catalyst was chosen with styrene and iodobenzene as substrates. The utilized precursor was Pd(acac)2, and the base K2CO3. The results are shown in Table 38.

Table 38. Key experiments for a Mizoroki-Heck reaction in multiphasic liquid/liquid systems with surfactants Preformation time Y in % CTAB 72 SDS 85 Marlipal 25/70 60 CTAB + co-solvent 89 Reaction conditions: [Pd]:[TPPTS]:[Substrate]:[K2CO3] = 1:6:500:500, 15 mmol styrene and iodobenzene, 15 ml H2O, 90 °C, 700 rpm, 4 h

In these reactions, the results are similar to literature results.[89] Because the Mizoroki-Heck reaction with these substrates does not form homo coupling products, unlike the Suzuki- Miyaura coupling reaction, the conversion of the substrates was taken as yield. The phase separation was not good in these reactions. The best one was with CTAB, where a small non- polar phase was visible after the reaction. Because the yield did not differ too much from the reaction with SDS, CTAB was chosen for the further investigation of the phase behavior. Toluene was chosen again as a co-solvent, and a subsequent reaction was performed, in this case even improving the yield. The phase behavior, again, was however not improved. The images can be found in the appendix as Figure A22 and A23. 83

Both examples show that the key experiments in these cases do seem to work. They show the viability with a simplified reaction approach, indicating that it is worth looking further into this multiphasic approach. Where they don’t manage to give final answers is the phase behavior and the finalized process. However, that is not the goal of these quick tests. Key experiments like these can be done for all kind of reaction systems in order to determine which ones are worth pursuing and optimizing. As mentioned earlier, the key experiments do need a theoretical assessment first, however. Simply trying reactions in all available systems is not the idea of this approach.

4 Summary and outlook

The goal of this thesis was to keep exploring options that benefit from the selectivity and atom efficiency of a molecular catalyst, while also being able to recycle the catalyst. The approach that was chosen to achieve this was a reaction system with two immiscible liquid phases. One phase was chosen to be an aqueous phase that contains a water soluble, molecular catalyst, while a non-polar substrate forms another phase. For an industrial hydroformylation of long chain alkenes, using a selective, molecular Rh catalyst while being able to recycle it, would be very desirable. So for this work the hydroformylation reaction of mainly 1-octene was chosen as a model reaction. The first approach used micelle-like polymer particles as phase transfer agents. The second approach didn’t use any specific phase transfer agents and made use of high pressure and high stirring rates to still reach good conversions. Finally the availability of different multiphasic solutions begs the question, which way to go. To be able to arrive to a well suited reaction system for a given reaction, a systematic approach was proposed in the final chapter. With the developed approach, the applicability of a reaction system can be checked. A micellar, multiphasic process was chosen to develop the process, as there is more literature data available for micellar systems.

To investigate the reaction system that utilizes micelle-like polymer particles, those particles have been thoroughly investigated. First, their synthesis was optimized. The particles were characterized by a range of techniques, like SEM, TEM and DLS. This work has also been published.[77] Their properties as catalyst carriers could also be proven, which was previously only assumed. Multiple reactions with these particles have then been performed. One aspect of the reaction system with polymer particles, that has not been mentioned in previous publications, the post-reaction phase separation, was described. It turned out that the formation of stable Pickering emulsions posed serious problems to the product separation and catalyst recycling. The separation could be improved by reducing stirring rates as well as reducing the amount of catalyst. It was a surprise in fact that reducing the amount of catalyst, at constant metal/ligand ratio still led to high conversion and reasonable selectivity. By increasing the ligand to metal ratio, a good conversion and selectivity could be reached, while maintaining 85 good phase separation. These results have also been published.[80] Further investigations aimed at avoiding or removing the Pickering emulsions. It was found that it is possible to recycle the catalyst together with the aqueous phase and Pickering emulsion, when removing the macro emulsion without accumulating the Pickering emulsion. This gives way to a process that allows a molecular catalyst, which can be recycled without relevant leaching into the product phase and a fairly easy product separation. The particle system has then also been applied to different substrates, as well as to a different reaction; the Miyaura-Suzuki reaction, to show that the concept is viable for more than just one kind of reaction. All the results finally lead to the conclusion that, unlike previously assumed, the particles seem not to act as microreactors, but instead probably more so as catalyst carriers. That means the catalyst sticks to the particles, while those preferably reside at the interface. This means that the particles carry the catalyst directly to the substrate, enabling high conversion, while also leading to good selectivity, because of the locally high ligand concentration on the particle surface.

Another multiphasic approach with two different liquid phases has been investigated, namely one without added phase transfer agents. It should be mentioned though, that the TPPTS-ligand and its complexes have some surface activity. This system has, to the best knowledge of the author, been only described by one group in literature.[52–55] The system does seem to require either high pressures or very intense mixing, for example by a jet loop reactor, but then it yields good results. In this work, utilizing simple stirred tank reactors in semi batch operation mode, the selectivity of the particle system could not be reached. While the particle system does offer advantages, the simplicity of the particle-free system is certainly striking. Not only does it not require the synthesis of polymer particles or any other phase transfer agent, but also avoids contamination of the product phase by those agents. In addition to that, the separation of the product after the reaction is extremely easy, even when using high stirring rates during the reaction, as no stable emulsion or foam is formed. The reaction system has been investigated for different parameters like stirring rate and pressure of synthesis gas. Under some conditions, it appears that unselective Rh-carbonyl species are formed, which go into the substrate phase, where they perform homogeneous catalysis. This brings a significant loss in selectivity and leads to the question of Rh leaching. Interestingly though, the Rh leaching was not high at all for most

86 of these reactions. It seems that, even in the case of an unselective Rh carbonyl species being the active catalyst, the Rh was extracted after the reaction by the polar phosphine ligands in the aqueous phase during depressurization. Importantly, the low selectivity was not always present. Under some conditions the selectivity was almost at the level of the particle system, while having reasonable reaction rates. This would be a system that is well suited when additional phase transfer agents are better avoided. In these cases the reaction is suspected to take place at the interface between aqueous catalyst phase and substrate phase.

Finding good results in both, the multiphasic particle system and the one without phase transfer agents, multiphasic approaches have been looked at in general. With the goal in mind to find a catalyst that is selective and can be recycled, an evaluation strategy for multiphase reactions has been developed. The first step always has to be a theoretical assessment, likely ruling out some approaches due to chemical or physical properties of different multiphasic processes. The next proposed step is to conduct of a few standardized key experiments. To show their viability, these have been conducted for a micellar multiphase system. The micellar system was chosen over the particle system to compare the performed key experiments with the available literature results, as little data is available for the particle system. The key experiments were in agreement with the literature, suggesting that they are a good way to check actual viability of a multiphasic reaction approach, after finding no theoretical problem with it. A third and final step in this evaluation strategy would be an optimization, which would then be done for the specific requirements for a given reaction and situation, after the first two steps were successful.

5 Experimental part

Most of the experimental procedures have been published before, and in those cases the experimental part is taken from the publications.[77,80]

5.1 Chemicals

The commercial products used for the synthesis of the monomers and for the polymer particles were used as received: styrene (Sigma-Aldrich, ≥99%), p-divinylbenzene (Sigma-Aldrich, 55% and 85%), sodium tetrafluoroborate (Sigma-Aldrich, ≥98%) p-vinylbenzyltrimethylammonium chloride (Sigma-Aldrich, 99%), vinylbenzyl chloride (Sigma-Aldrich, 90%), poly(ethylene glycol) methyl ether (Sigma-Aldrich, average Mn 2000) and the initiator 2,2'-azobis[2-methyl-N-(2- hydroxyethyl)propionamide] (VA-086) (Alpha Laboratories Ltd, +98.0%). For the hydroformylation experiments, 1-octene (Sigma Aldrich, 98%) and the other substrates (1-hexene (Alfa Aesar, 98 %), 1-decene (Sigma-Aldrich, 94 %), cyclohexene (Sigma-Aldrich 99 %), Eugenol (Alfa Aesar, 99 %) were filtered through alumina and Ar was bubbled through it to remove oxygen before use. [Rh(acac)(CO)2] (abcr, 99%), TPPTS (Sigma-Aldrich, ≥95) and n- dodecane (Sigma-Aldrich, ≥99%) were used as received from the commercial sources. THF was dried by distillation over Na and benzophenone. Acetonitrile, CH2Cl2, diethyl ether, 1,4-dioxane and HPLC-grade water were used as received. Danphos, [83] Dan2phos [90] and TPPDS [91] ligands were prepared according to the literature.

5.2 Preparation of the monomers

(p-Vinylbenzyl)trimethylammonium tetrafluoroborate (SS). The styrene derivative salt was synthesized following the procedure described in literature.[92]

31.8 g of p-vinylbenzyltrimethylammonium chloride (150 mmol) and 18.3 g of NaBF4 (167 mmol) were stirred overnight in 200 ml of acetonitrile. The formed precipitate was removed by filtration and the filtrate was concentrated until a white solid started to precipitate. The addition of 200 ml of diethyl ether caused the precipitation of a white solid that was filtered off. The white precipitate was washed with diethyl ether and dried under vacuum.

1 3 3 H NMR (500,23 MHz, DMSO-d6) δ 7.61 (d, 2H, Ph, J= 8.3 Hz), 7.51 (d, 2H, Ph, J= 8.3 Hz), 6.80

3 3 3 (dd, 1H, CH=CH2, J= 11.1 Hz, J= 17.7 Hz), 5.95 (d, 1H, CH=CHH, J= 17,7 Hz), 5.38 (d, 1H,

3 CH=CHH, J= 11.1 Hz), 4.49, (s, 2H, CH2), 3.02 (s, 9H, CH3). p-(Vinylbenzyl)poly(ethyleneglycol) (VB-PEG). The synthetic procedure was slightly modified from the one previously reported in the literature[93] for compounds with different poly(ethyleneglycol) lengths.

50.0 g of poly(ethylene glycol) methyl ether (molar mass = 2000, 25.0 mmol) were introduced in a Schlenk flask containing 250 ml of dried THF. NaH (1.0 g, 42.0 mmol) was introduced to the suspension under vigorous stirring during one hour. A solution of vinylbenzyl chloride (23.0 mmol) in 20 ml of dry THF was added drop-wise via a compensated pressure funnel and the mixture was refluxed for 20 hours. After cooling the mixture to room temperature, it was neutralized with HCl (1M) and the product was extracted with 300 ml of CH2Cl2. The organic phase was separated and the aqueous phase was extracted with CH2Cl2 (2 x 50 ml). The combined organic phases were dried with Na2SO4. The organic solution was concentrated in vacuum. The addition of 300 ml of diethyl ether caused the precipitation of the product that was filtered, washed with diethyl ether (3x50 ml) and dried under vacuum.

1 3 3 H NMR (500.12 MHz, D2O) δ 7.57 (d, 2H, Ph, J= 7,6 Hz), 7.45 (d, 2H, Ph, J= 7,6 Hz), 6,85 (dd,

3 3 3 1H, CH=CH2, J= 11.1 Hz, J= 17.6 Hz), 5.92 (d, 1H, CH=CHH, J= 17,6 Hz), 5.38 (d, 1H, CH=CHH,

3 J= 11.1 Hz), 4.63, (s, 2H, C6H4CH2), 3,72 (m, 190H, OCH2CH2O), 3.42 (s, 3H, CH3).

5.3 Polymer particle preparation

(p-Vinylbenzyl)trimethylammonium tetrafluoroborate (SS) and p-(vinylbenzyl)poly- (ethyleneglycol) were dissolved in water in a glass autoclave equipped with mechanical stirring under inert atmosphere and the solution was warmed to 80°C. Styrene and p-divinylbenzene were added to the mixture and subsequently a solution of the initiator (1% mol) in water was added to the emulsion. The reaction was kept for 4 hours at 80°C. After this period, the reaction was cooled to room temperature and the suspension was dialyzed for 5 days in a cellulose dialysis tube of 14000 Da molecular weight cut-off. Finally, the samples were stored at 4°C. In

89 earlier samples, the PEG-monomer was added after the initiator, which leads to more agglomeration. The setup with the glass reactor can be seen in Figure 40.

Solid residue: To analyze the solid residue of the different samples, 2 ml of polymer particle suspension were added to a round bottom flask and the water was removed by a freeze-drying process. Finally, after the dehydration process the solid residue was weighted.

Figure 40. Reactor setup for particle synthesis

5.4 Catalyst carrier experiments

The precursor [Rh(acac)(CO)2] and the ligand TPPTS were dissolved in 10 ml of an aqueous suspension of polymer particles (25 mg/ml). Once the catalyst precursor and the ligand were completely dissolved, the mixture was transferred to a centrifuge tube equipped with a membrane filter of 10000 Da). The samples were centrifuged at 2500 rpm for one hour. 5 ml of the filtrate were stirred with 1 ml of aqua regia overnight and the solution was diluted with 7 ml of distilled water and analyzed by ICP-OES.

5.5 Catalytic reactions and related procedures

5.5.1 1-Octene hydroformylation

[Rh(acac)(CO)2] and the phosphine ligands were introduced in the autoclave under argon, together with the polymer particles suspended in 20 ml of water. 1-Octene (150 mmol) and n-dodecane (15 mmol) as internal standard were introduced in a compensated-pressure addition funnel connected to the autoclave. The system was then pressurized to 100 bar of syngas (1:1) and heated to 80°C at the corresponding stirring rate. After 1 hour of catalyst preformation, the substrate and standard were added to the catalyst aqueous phase and the gas consumption was recorded. After 22 hours, the temperature was lowered to 65°C and the autoclave was slowly depressurized, after which it was cooled to room temperature. A droplet of the organic phase was diluted with diethyl ether and analyzed by GC to calculate the conversion and the selectivity of the reaction. The TOF was calculated from the gas uptake.

5.5.2 Hydroformylation of other 1-alkenes

The same procedure as for 1-octene was used for the rest of the 1-alkenes tested. Only the internal standard was changed in order not to interfere during the GC analysis. For the hydroformylation of 1-hexene, n-dodecane was used as standard; toluene was used for 1- decene hydroformylation and n-decane for the hydroformylation of 1-dodecene.

5.5.3 Recycling experiments with centrifugation

After the first run, the reaction mixture was transferred to a centrifuge tube, and the mixture was centrifuged for 15 min at 3000 rpm. The aqueous phase was then transferred to a Schlenk flask, purged with argon during 10 min, and reused as catalyst phase for the second run. The process was repeated 3 times.

5.5.4 Recycling experiments including the Pickering emulsion

The reaction mixture was taken out of the autoclave after the reaction. The macroscopic emulsion was carefully destroyed using a pipette to poke the bubbles. The residual PE and aqueous phase were then degassed for 20 minutes and recycled in the reactor. 91

5.5.5 Recycling experiments with diethyl ether for phase separation

After the first run, the reaction mixture was transferred to a separation funnel and the nonpolar components were extracted with 50 ml of diethyl ether. The aqueous phase was then transferred to a Schlenk flask, and Ar was bubbled through it to remove oxygen for 10 min. The aqueous phase was then reused as the catalyst phase for the second run. The process was repeated 3 times.

5.5.6 Recycling experiments without polymer particles

The reaction mixture was taken out of the reactor and the product phase was taken with a pipette. After bubbling nitrogen through the aqueous phase for 20 min, it was returned to the autoclave, which was under inert gas.

5.5.7 Multiphasic hydroformylation reaction with surfactants

The reactions were done analogous to the hydroformylations with polymer particles. But the surfactant was added instead of the polymer particle suspension.

5.5.8 Suzuki-Miyaura and Mizoroki-Heck coupling reactions

Standard conditions for working under oxygen free conditions were utilized. The solid compounds except for the catalyst were added to a 50 ml three neck Schlenk flask. The liquid compounds were then added, this includes the polymer particle solution if utilized. The reaction was heated to the reaction temperature and then the catalyst, solubilized in water, was added.

5.6 Instruments and characterization methods

5.6.1 Surface tension (SFT) and critical micelle concentration (cmc)

To determine the cmc of the VB-PEG chains, the surface tension of VB-PEG solutions at different concentrations was investigated. To analyze the data, DCAT 11 of DataPhysics were used. The surface tension was measured with the method of Du Noüy. The ring material is platinum- iridium and the dimensions of the ring are: height = 25 mm, diameter = 18.7 mm and thickness = 0.37 mm. Before every measurement, at the different VB-PEG concentrations, the ring was 92 flame-cleaned. To ensure that the VB-PEG molecules are at the interface, an equilibrium time of 4 min was applied.

5.6.2 Dynamic light scattering (DLS)

Suspensions of polymer particles were diluted until the sample was slightly turbid. The data were recorded using a LS Instruments spectrometer. The temperature was adjusted at 25 °C for all measurements and was controlled by a Julabo CF 31 cryostat.

5.6.3 Visual microscopy with UV-active dyes

A dye, either Nilred or Uranine were added to mixtures of 1-octene and water. These were then manually shaken for one minute, before analyzing them.

5.6.4 Atomic force microscopy (AFM)

The samples were diluted to a concentration of 0.05 wt. %. 80 µl of the diluted sample was pipetted on a 1x1 cm2 silicon waver, which one was cleaned with MilliQ water. The sample on the silicon waver was immediately spin coated at 2000 rpm for 5 min. The AFM measurements were done by Asylum Research Cypher with an ac160tc (Olympus) cantilever. The measurements were done in intermittent contact mode. In this mode, it is possible to get the high image and the phase image. Before analyzing the data, the pictures were first order flatted.

5.6.5 Transmission electron microscopy (TEM)

For the TEM measurements a LVEM5 from Delong instruments was used. As a sample holder, a copper grid that was pretreated in a plasma cleaner to discharging it, was used. All samples had a concentration of 0.1 wt%. A droplet of the particle suspension was spread on a copper grid. After 30 s the residual droplet was removed with filter paper and the sample was analyzed. The acceleration voltage was between 4.9 and 5.1 kV.

5.6.6 Scanning electron microscopy (SEM)

For the SEM measurements, the already prepared samples from the AFM measurements were used. The samples were analyzed with a Hitachi SU8030 instrument equipped with a cold field emitter.

5.6.7 Zeta potential

The zeta potential was measured with a Zetasizer Nano ZS from Malvern in back scattering (173 °) mode. The concentrations of the samples were 0.005 wt. %. The measurements were done at 25 °C and after 120 s waiting time.

5.6.8 Nuclear magnetic resonance (NMR)

The spectra were recorded on a Bruker Avance III 500 MHz spectrometer. Chemicals shifts are given in delta (δ) units in ppm relative to the residual solvent peak. The multiplicity of the proton signals is given as s (singlet), d (doublet), dd (doublet of doublets) and m (multiplet).

5.6.9 Gas chromatography (GC)

The catalytic reactions were analyzed using a Shimadzu GC-2010 instrument equipped with a flame ionization detector (FID) detector and an Ultra-19091B-102 capillary column (25.0 m, 0.20 mm ID) from Agilent. The following temperature program was used: 50° C (7 min);

20 °C/min until 280 °C; 280 °C (3 min). Tinjector = 280 °C; Tdetector = 305 °C.

5.6.10 Inductively coupled plasma optical emission spectrometry (ICP- OES)

The samples were analyzed using a Perkin Elmer Optima 5300 DV, employing an RF forward power of 1400 W, with argon gas flows of 15, 0.2 and 0.75 L/min for plasma, auxiliary, and nebuliser flows, respectively. Using a peristaltic pump, sample solutions were taken up into a Gem Tip cross-Flow nebuliser and Scotts spray chamber at a rate of 1.50 mL/min.

5.6.11 Inductively coupled plasma mass spectrometry (ICP-MS)

Samples were analyzed by ICP-MS using an Agilent 7500ce (with octopole reaction system), employing an RF forward power of 1540 W and reflected power of 1 W, with argon gas flows of 0.81 L min-1 and 0.19 L min-1 for carrier and makeup flows, respectively. Sample solutions were taken up into the Micro mist nebuliser by peristaltic pump at a rate of approximately 1.2 mL min-1. Skimmer and sample cones were made of nickel. The instrument was operated in spectrum acquisition mode and three replicate runs per sample were employed. The mass analyzed for the metal was 103Rh. Each mass was analyzed in fully quant mode (three points per unit mass).

6 Literature

[1] P. Anastas and J. C. Warner, Green Chemistry: Theory and Practice, Oxford University Press, 1998.

[2] R. A. Sheldon, Green Chem. 2017, 19, 18–43.

[3] A. Behr, P. Neubert, Applied Homogenous Catalysis, Wiley-VCH, 2012.

[4] R. A. Sheldon, Chem. Ind. 1992, 903–906.

[5] C. Capello, U. Fischer, K. Hungerbühler, Green Chem. 2007, 9, 927.

[6] B. H. Lipshutz, N. a. Isley, J. C. Fennewald, E. D. Slack, Angew. Chemie - Int. Ed. 2013, 52, 10952–10958.

[7] M. J. Muldoon, Dalt. Trans. 2010, 39, 337–348.

[8] A. Z. Fadhel, P. Pollet, C. L. Liotta, C. A. Eckert, Annu. Rev. Chem. Biomol. Eng. 2011, 2, 189–210.

[9] L. Obrecht, P. C. J. Kamer, W. Laan, Catal. Sci. Technol. 2013, 3, 541–551.

[10] I. Vural Gürsel, T. Noël, Q. Wang, V. Hessel, Green Chem. 2015, 17, 2012–2026.

[11] R. Franke, D. Selent, A. Börner, Chem. Rev. 2012, 112, 5675–5732.

[12] D. J. Cole-Hamilton, Catalyst Separation, Recovery and Recycling, Springer Netherlands, 2006.

[13] P. W. N. M. van Leeuwen, Homogeneous Catalysis, Kluwer Academic Publishers, 2004.

[14] I. Volovych, Y. Kasaka, M. Schwarze, Z. Nairoukh, J. Blum, M. Fanun, D. Avnir, R. Schomäcker, J. Mol. Catal. A Chem. 2014, 393, 210–221.

[15] M. Schwarze, T. Pogrzeba, I. Volovych, R. Schomäcker, Catal. Sci. Technol. 2015, 5, 24–33.

[16] Y. Kasaka, B. Bibouche, I. Volovych, M. Schwarze, R. Schomäcker, Colloids Surfaces A Physicochem. Eng. Asp. 2016, 494, 49–58. 96

[17] T. Pogrzeba, D. Müller, T. Hamerla, E. Esche, N. Paul, G. Wozny, R. Schomäcker, Ind. Eng. Chem. Res. 2015, 54, 11953–11960.

[18] T. Pogrzeba, Mechanistische Untersuchungen Zur Hydroformylierung von Lang- Kettigen Olefinen in Wässriger Tensidlösung, 2013.

[19] M. Illner, D. Müller, E. Esche, T. Pogrzeba, M. Schmidt, R. Schomäcker, G. Wozny, J. U. Repke, Ind. Eng. Chem. Res. 2016, 55, 8616–8626.

[20] T. Pogrzeba, M. Schmidt, N. Milojevic, C. Urban, M. Illner, J. U. Repke, R. Schomäcker, Ind. Eng. Chem. Res. 2017, 56, 9934–9941.

[21] F. Hapiot, A. Ponchel, S. Tilloy, E. Monflier, Comptes Rendus Chim. 2011, 14, 149–166.

[22] F. Hapiot, H. Bricout, S. Menuel, S. Tilloy, E. Monflier, Catal. Sci. Technol. 2014, 4, 1899– 1908.

[23] M. Elard, J. Denis, M. Ferreira, H. Bricout, D. Landy, S. Tilloy, E. Monflier, Catal. Today 2015, 247, 47–54.

[24] K. Kunna, Catalyst Immobilization via Electrostatic Interactions: Polystyrene-Based Supports, 2009.

[25] K. Kunna, C. Müller, J. Loos, D. Vogt, Angew. Chemie - Int. Ed. 2006, 45, 7289–7292.

[26] H. Nowothnick, A. Rost, T. Hamerla, R. Schomäcker, C. Müller, D. Vogt, Catal. Sci. Technol. 2013, 3, 600–605.

[27] A. F. Cardozo, C. Julcour, L. Barthe, J. Blanco, S. Chen, F. Gayet, E. Manoury, X. Zhang, M. Lansalot, B. Charleux, et al., J. Catal. 2015, 324, 1–8.

[28] E. Lobry, A. F. Cardozo, L. Barthe, J. Blanco, H. Delmas, S. Chen, F. Gayet, X. Zhang, M. Lansalot, F. D. Agosto, et al., J. Catal. 2016, 342, 164–172.

[29] S. L. Desset, S. W. Reader, D. J. Cole-Hamilton, Green Chem. 2009, 11, 630.

[30] I. Volovych, M. Neumann, M. Schmidt, G. Buchner, J. Y. Yang, J. Wölk, T. Sottmann, R. Strey, R. Schomäcker, M. Schwarze, RSC Adv. 2016, 6, 58279–58287.

[31] R. Skouta, Selective Chemical Reactions in Supercritical Carbon Dioxide, Water, and Ionic Liquids, 2009.

[32] S. Keskin, D. Kayrak-Talay, U. Akman, Ö. Hortaçsu, J. Supercrit. Fluids 2007, 43, 150–180.

[33] M. F. Sellin, P. B. Webb, D. J. Cole-hamilton, J. Am. Chem. Soc. 2001, 125, 781–782.

[34] T. E. Kunene, P. B. Webb, D. J. Cole-Hamilton, Green Chem. 2011, 13, 1476–1481.

[35] P. W. N. M. Van Leeuwen, P. C. J. Kamer, Catal. Sci. Technol. 2018, 8, DOI 10.1039/c7cy01629h.

[36] M. Kranenburg, Y. E. M. van der Burgt, P. C. J. Kamer, P. W. N. M. van Leeuwen, K. Goubitz, J. Fraanje, Organometallics 1995, 14, 3081–3089.

[37] Y. Brunsch, A. Behr, Angew. Chemie - Int. Ed. 2013, 52, 1586–1589.

[38] T. Gaide, J. M. Dreimann, A. Behr, A. J. Vorholt, Angew. Chemie - Int. Ed. 2016, 55, 2924– 2928.

[39] J. M. Dreimann, F. Hoffmann, M. Skiborowski, A. Behr, A. J. Vorholt, Ind. Eng. Chem. Res. 2017, 56, 1354–1359.

[40] P. G. Jessop, S. M. Mercer, D. J. Heldebrant, Energy Environ. Sci. 2012, 5, 7240–7253.

[41] P. Pollet, R. J. Hart, C. A. Eckert, C. L. Liotta, Acc. Chem. Res. 2010, 43, 1237–1245.

[42] A. Z. Fadhel, P. Pollet, C. L. Liotta, C. A. Eckert, Molecules 2010, 15, 8400–8424.

[43] J. P. Hallett, J. W. Ford, R. S. Jones, P. Pollet, C. A. Thomas, C. L. Liotta, C. A. Eckert, Ind. Eng. Chem. Res. 2008, 47, 2585–2589.

[44] S. M. Mercer, T. Robert, D. V. Dixon, P. G. Jessop, Catal. Sci. Technol. 2012, 2, 1315.

[45] S. L. Desset, D. J. Cole-Hamilton, Angew. Chemie - Int. Ed. 2009, 48, 1472–1474.

[46] M. Mokhadinyana, S. L. Desset, D. B. G. Williams, D. J. Cole-Hamilton, Angew. Chemie - Int. Ed. 2012, 51, 1648–1652.

[47] R. L. Vekariya, J. Mol. Liq. 2017, 227, 40. 98

[48] A. Riisager, R. Fehrmann, M. Haumann, P. Wasserscheid, Eur. J. Inorg. Chem. 2006, 695– 706.

[49] H.-P. Steinrueck, P. Wasserscheid, Coord. Chem. Rev. 2004, 248, 2459–2477.

[50] S. Walter, H. Spohr, R. Franke, W. Hieringer, P. Wasserscheid, M. Haumann, ACS Catal. 2017, 7, 1035–1044.

[51] M. Schmidt, T. Pogrzeba, L. Hohl, A. Weber, A. Kielholz, M. Kraume, R. Schomäcker, Mol. Catal. 2017, 439, 1–8.

[52] H. Warmeling, R. Koske, A. J. Vorholt, Chem. Eng. Technol. 2017, 40, 186–195.

[53] H. Warmeling, A. C. Schneider, A. J. Vorholt, AIChE J. 2018, 64, 161–171.

[54] H. Warmeling, D. Hafki, T. von Söhnen, A. J. Vorholt, Chem. Eng. J. 2017, 326, 298–307.

[55] H. Warmeling, D. Janz, M. Peters, A. J. Vorholt, Chem. Eng. J. 2017, 330, 585–595.

[56] B. Pinho, R. L. Hartman, React. Chem. Eng. 2017, 2, 189–200.

[57] S. U. Pickering, J. Chem. Soc., Trans. 1907, 91, 2001–2021.

[58] W. Ramsden, Proc. R. Soc. London 1904, 72, 156–164.

[59] Y. Zhao, X. Zhang, J. Sanjeevi, Q. Yang, J. Catal. 2016, 334, 52–59.

[60] T. Skale, D. Stehl, L. Hohl, M. Kraume, R. von Klitzing, A. Drews, Chemie-Ingenieur-Technik 2016, 88, 1827–1832.

[61] D. Stehl, L. Hohl, M. Schmidt, J. Hübner, M. Lehmann, M. Kraume, R. Schomäcker, R. von Klitzing, Chemie-Ingenieur-Technik 2016, 88, 1806–1814.

[62] C. Disser, C. Muennich, G. Luft, Appl. Catal. A Gen. 2005, 296, 201–208.

[63] Z. He, Z. Hou, Y. Zhang, T. Wang, Y. Dilixiati, W. Eli, Catal. Today 2015, 247, 147–154.

[64] M. M. Diwakar, R. M. Deshpande, R. V. Chaudhari, J. Mol. Catal. A Chem. 2005, 232, 179– 186.

[65] F. Cozzi, Adv. Synth. Catal. 2006, 348, 1367–1390.

[66] P. McMorn, G. J. Hutchings, Chem. Soc. Rev. 2004, 33, 108–122.

[67] B. G. P. van Ravensteijn, D.-J. Schild, W. K. Kegel, R. J. M. Klein Gebbink, ChemCatChem 2017, 9, 440–450.

[68] X. Jiang, Polymer (Guildf). 2010.

[69] J. N. H. Reek, S. Arévalo, P. C. J. van Heerbeek, Rieko Kamer, P. W. N. M. van Leeuwen, Adv. Catal. 2006, 49, 71–151.

[70] C. Williams, M. Ferreira, E. Monflier, S. F. Mapolie, G. S. Smith, Dalt. Trans. 2018, 47, 9418–9429.

[71] A. Falk, J. M. Dreimann, D. Vogt, ACS Sustain. Chem. Eng. 2018, 6, 7221–7226.

[72] T. Gaide, A. Behr, A. J. Vorholt, Catalysis by Metal Complexes, Vol. 39, Springer International Publishing, 2017.

[73] S. Raoufmoghaddam, Org. Biomol. Chem. 2014, 12, 7179–7193.

[74] A. Jörke, A. Seidel-Morgenstern, C. Hamel, J. Mol. Catal. A Chem. 2017, 426, 10–14.

[75] M. Lemberg, G. Sadowski, M. Gerlach, E. Kohls, M. Stein, C. Hamel, A. Seidel- Morgenstern, AIChE J. 2017, 63, 4576–4585.

[76] E. Kohls, M. Stein, New J. Chem. 2017, 41, 7347–7355.

[77] D. Peral, D. Stehl, B. Bibouche, H. Yu, J. Mardoukh, R. Schomäcker, R. Von Klitzing, D. Vogt, J Colloid Interface Sci 2018, 513, 638–646.

[78] H. B. Yamak, Emulsion Polymerization : Effects of Polymerization Variables on the Properties of Vinyl Acetate Based Emulsion Polymers, IntechOpen, 2013.

[79] M. Gumustas, C. T. Sengel-Turk, A. Gumustas, S. A. Ozkan, B. Uslu, Multifunctional Systems for Combined Delivery, Biosensing and Diagnostics, Chapter 5 - Effect of Polymer- Based Nanoparticles on the Assay of Antimicrobial Drug Delivery Systems, Elsevier Inc., 2017. 100

[80] B. Bibouche, D. Peral, D. Stehl, V. Söderholm, R. Schomäcker, R. Von Klitzing, D. Vogt, RSC Adv. 2018, 8, 23332–23338.

[81] M. Gerlach, D. Abdul Wajid, L. Hilfert, F. T. Edelmann, A. Seidel-Morgenstern, C. Hamel, Catal. Sci. Technol. 2017, 7, 1465–1469.

[82] M. Haumann, H. Koch, P. Hugo, R. Schomäcker, Appl. Catal. A Gen. 2002, 225, 239–249.

[83] D. Peral, D. Herrera, J. Real, T. Flor, J. C. Bayón, Catal. Sci. Technol. 2015, 6, 800–808.

[84] M. Rahman, H. Liu, K. Eriks, A. Prock, W. P. Giering, Organometallics 1989, 8, 1–7.

[85] D. R. Palo, C. Erkey, Organometallics 2000, 38, 81–86.

[86] C. C. C. Johansson Seechurn, M. O. Kitching, T. J. Colacot, V. Snieckus, Angew. Chemie - Int. Ed. 2012, 51, 5062–5085.

[87] A. Chatterjee, T. R. Ward, Catal. Letters 2016, 146, 820–840.

[88] D. Roy, Y. Uozumi, Adv. Synth. Catal. 2018, 360, 602–625.

[89] H. Nowothnick, J. Blum, R. Schomäcker, Angew. Chemie - Int. Ed. 2011, 50, 1918–1921.

[90] D. Peral Crespo, J. C. Bayón Rueda, Triphenylphosphine Derivatives, 2011, WO2011045417 A1.

[91] T. Thorpe, S. M. Brown, J. Crosby, S. Fitzjohn, J. P. Muxworthy, J. M. J. Williams, Tetrahedron Lett. 2000, 41, 4503–4505.

[92] J. Tang, H. Tang, W. Sun, H. Plancher, M. Radosz, Y. Shen, Chem Commun 2005, 26, 3325– 3327.

[93] H. Fengjun, W. Yuan, P. F. Britt, J. W. Mays, K. Hong, Soft Matter 2013, 9, 8897–8903.

101

102

7 Appendix

7.1 Publications

 Y. Kasaka, B. Bibouche, I. Volovych, M. Schwarze, R. Schomäcker, Colloids Surfaces A Physicochem. Eng. Asp. 2016, 494, 49–58  D. Peral, D. Stehl, B. Bibouche, H. Yu, J. Mardoukh, R. Schomäcker, R. Von Klitzing, D. Vogt, J Colloid Interface Sci 2018, 513, 638–646  B. Bibouche, D. Peral, D. Stehl, V. Söderholm, R. Schomäcker, R. Von Klitzing, D. Vogt, RSC Adv. 2018, 8, 23332–23338

103

7.2 Additional information

100

99,5

98,5

Conversion (%) Conversion 98

97,5

97 0 10 20 30 40 50 60 70 80 90 100 110 120 Time (min) Figure A1. Styrene consumption by GC analysis during the synthesis of the polymer particles

99,5

98,5

98 Conversion (%) Conversion 97,5

97 0 1 2 3 4 5 6 Time (min) Figure A2. Styrene consumption by 1H-NMR analysis during the synthesis of the polymer particles

104

92 91 90 89 88 87

86 Conversion (%) Conversion 85 84 83 0 2 4 6 8 10 12 Time (min) Figure A3. Styrene-salt consumption by 1H-NMR analysis during the synthesis of the polymer particles

Figure A4. Polymer particle suspenisons, with the compositions shown in Table 7[77]

Figure A5. AFM image of a single particle in phase mode, showing the core and shell of a particle[77] 105

Figure A6. Centrifugation experiments with Rh- TPPTS in solution with left) water, middle) polymer particles with cationic moieties and right) polymer particles without cationic moieties[77]

Figure A7. Microscopy images from the emulsion phase of a reaction mixture.

106

Figure A8. Reaction mixture of the reactions with a [S]:[Rh] ratio of 5000 (left) and 1:80000 (right), the specifications can be found in Table 11. On the left there is no clear product phase, while on the right there is some Pickering emulsion and a big amount of clear product phase.

Figure A9. Phase separation after the 1-octene hydroformylation with LX2 at 700 rpm (left) and 300 rpm (right). Reaction conditions: 0.03 mmol [Rh(acac)(CO)2], 0.18 mmol TPPTS, 150 mmol 1- octene, [C]:[L]:[S] = 1:6:5000, 15 mmol n-dodecane as internal standard. 500 mg of particles, 20 ml 0 H2O. 80 C, 100 bar CO:H2 (1:1), 22 h.

107

Figure A10. Left: the purple indicator shows the expected reaction volume versus the obtained reaction volume, shown by the purple indicator on the right. Depressurization of the reaction system after a reaction through a transparent exhaust line shows a unrecoverable loss of reaction mixture.

Figure A11. Reaction shown Figure A12. Reaction with in Table 19, with 1500 rpm styrene shown in Table 20. A and 100 °C. While an large Pickering emulsion is aqueous phase is visible at obtained, despite a very low the bottom, the upper phase stirring rate of 350 rpm is only a Pickering emulsion [Rh]:[L]:[S] = 1:20:40000 with no clear oil phase.

108

Figure A13. Reaction shown in Figure A14. Phase separation of a post reaction Table 21 with a stirring rate of Pickering emulsion (3 ml) with the addition of 1050 rpm [Rh]:[L]:[S] = 1:6:1000 different co-solvents (3 ml), 1: glycerol 2: 1,4-dioxane 3: methanol

Figure A15. Reaction mixtures of hydroformylation reactions with particles, see Table 24. Left; with 1,4-dioxane as a coslovent, right; no co-solvent

109

Figure A16. Reaction mixtures of hydroformylation reactions with particles, see Table 25. Left; with methanol as a coslovent, right; no co-solvent

Figure A17. Reaction mixture Figure A18. Reaction mixture after centrifugation described in Figure 29, after the reaction

Figure A19. Reaction mixture described Figure A20. Hydroformylation in Figure 30, after the reaction with 5 ml reaction with CTAB, without co- of t-amylalcohol as a co-solvent and then solvent an additional 15 ml after the reaction. 110

Figure A21. Hydroformylation Figure A22. Mizoroki-Heck reaction reaction with CTAB, containing with CTAB, without co-solvent toluene as a co-solvent

Figure A23. Mizoroki-Heck reaction with CTAB, containing toluene as a co-solvent

111

7.3 Danksagung

Als erstes möchte ich Herrn Prof. Dr. Dieter Vogt danken, welcher das spannende Thema bereit gestellt hat und mich während meiner gesamten Promotion bestens unterstützt und betreut hat. Gleiches gilt für Prof. Dr. Reinhard Schomäcker, der mich nicht nur unterstützt und betreut hat, sondern in dessen Arbeitsgruppe zudem ein Großteil der Arbeit verrichtet wurde. Auch an Frau Prof. Dr. Regine von Klitzing und Frau Prof. Dr. Anja Drews geht mein Dank für die Kooperation, Beratung und sehr gute Zusammenarbeit.

Riesengroßer Dank geht an Dr. Daniel Peral, der eine große Hilfe war und mit dem zu arbeiten stets ein Privileg und eine Freude war.

Großer Dank für die tolle Kooperation geht auch an Dmitrij Stehl, Prof. Dr. Michael Schwarze, Dr. Thomas Seidensticker und Viktor Söderholm. Vielen Dank auch an die Student*innen die bei der Arbeit beteiligt waren und die allesamt tolle Arbeit leisteten; Pablo Botero, Jonas Diekmann, Lukas Gottheil, Max von Grevenitz, Carlos Islas, Julius Kerstien, Joe Mardoukh, Sidharth Nair, Jan Reimann, Orhan Ünal, Katarzina Sawicka, Maxi Spiekermann und Hongxing Yu.

Danken möchte ich auch der gesamten Gruppe Reinhard Schomäckers und der Gruppe Dieter Vogts. Besonders hervorheben möchte ich Yasemin Kasaka, Annika Marxen, Ewa Nowicka und Samira Parishan die mir fachlich eine Hilfe waren aber vor allem sehr gute Freund*innen geworden sind. Außer den Arbeitsgruppen möchte dem gesamten SFB/Transregio 63 für die Hilfe danken, durch die Einbindung konnte ich viel lernen. Der Einsteinstiftung gebührt mein Dank für das Stipendium und die generelle finanzielle Unterstützung des Forschungsprojekts.

Großer Dank für die herausragende Arbeit und Hilfe die nicht nur ich, sondern alle in der Gruppe Schomäckers erfahren haben, geht an Gabriele Vetter und Christa Löhr. Außerdem danke ich Cornelia Löhmann, die sich sehr gut um u.a. die Finanzen und Organisation von Reisen gekümmert hat und mir und Daniel Peral viel ermöglicht hat. Astrid Müller-Klauke danke ich für die große Hilfe bei verschiedensten Messungen. Ich danke den gesamten Werkstätten der TU

112 Berlin, TU Dortmund und University of Edinburgh, dabei möchte ich Justin Ufer, Phillip Haseloff, Eric Sallwey, und Carsten Hirschfeld besonders hervorheben.

Außerdem möchte ich mich auch sehr bei meiner Familie bedanken, die mir immer geholfen hat. Ich bin wirklich sehr froh und Dankbar dafür! Aus meinem Freundeskreis danke ich besonders Athanasia, Benjamin, Markus und Rhea.

Der größte Dank geht an Maike Groen, die immer für mich da war und ist! Ich bin sehr froh über uns und deine Mithilfe hat mir sehr beim Bewältigen aller möglicher Aufgaben und Hindernisse geholfen.

113