Reactions and Separations in Green Solvents

Reactions and Separations

in

Green Solvents

Jaap van Spronsen

Reactions and Separations

in

Green Solvents

Proefschrift

ter verkrijging van de graad van doctor aan de Technische Universiteit Delft,

op gezag van de Rector Magnificus Prof. ir. K. C. A. M. Luyben, voorzitter van het College voor Promoties,

in het openbaar te verdedigen op dinsdag 8 juni 2010 om 10:00 uur

door

Jacob VAN SPRONSEN

doctorandus in de scheikunde geboren te Delft

Dit proefschrift is goedgekeurd door de promotoren: Prof. dr. G. J. Witkamp Prof. dr. R. Verpoorte Copromotor: Dr. ir. M. C. Kroon Samenstelling promotiecommissie: Rector Magnificus Voorzitter Prof. dr. G. J. Witkamp Technische Universiteit Delft, promotor Prof. dr. R. Verpoorte Universiteit Leiden, promoter Dr. ir. M. C. Kroon Technische Universiteit Delft, copromotor Prof. dr. ir. C. J. Peters Petroleum Institute, Abu Dhabi, UAE Prof. dr. G. A. van der Marel Universiteit Leiden Prof. dr. I. W. C. E. Arends Technische Universiteit Delft Prof. dr. ir. L. A. M. van der Wielen Technische Universiteit Delft ISBN: 978-90-9025387-9 Printed by Ipskamp Drukkers B.V. Copyright © 2010 by Jaap van Spronsen

All rights reserved. No part of the material protected by this copyright notice may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording or by any information storage and retrieval system, without written permission from the publisher.

Printed in Enschede, The Netherlands

Voor Petra, Eric, Laura en Abel

“Everything we hear is an opinion, not a fact.

Everything we see is a perspective, not the truth.”

Marcus Aurelius

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Summary Reactions and Separations in Green Solvents Most chemical processes involve solvents in the reaction and the separation step, to dissolve solids, to lower the viscosity, to regulate temperatures, to recover compounds by means of extraction or crystallization, as reaction medium or for cleaning purposes. However, solvents give rise to a heavy environmental and economical burden e.g., in the USA yearly around 15-20 million tons of volatile organic compounds are discharged into the atmosphere as a result of industrial processing operations. Moreover, these solvents are based on non-sustainable resources like petroleum. Ideally, solvent-free processes should be available, but this is not always possible. Instead alternative non-petroleum based environmentally friendly solvents such as water, supercritical or liquid carbon dioxide or certain ionic liquids may be employed. The aim of this thesis work has been to develop a number of alternative processes based on green solvents, and to demonstrate that these can be economically and ecologically advantageous compared to the classical processes. Water is used as environmentally benign solvent for the winning of soda and molybdate from waste water. This aqueous waste stream in the Rotterdam Port area (250 kton/year) is currently neutralized with sulfuric acid and subsequently disposed into the environment. In this thesis, it is shown that the waste water stream can be treated without the sulfuric acid by eutectic freeze crystallization, yielding valuable crystalline soda ash as a bonus. This was demonstrated by pilot experiments at the industrial location. Process design calculations proved a potential benefit of about 2.1 M€/year, which increases at increasing energy prices. Water can be replaced by supercritical carbon dioxide as solvent for the dyeing of cotton. Currently, cotton (20 billion kg/year) is dyed in water, using 100 liter of clean water per kg textile and producing the same amount of chemical waste containing hydrolyzed dye, salts and alkali. When supercritical carbon dioxide is used as solvent instead, this water consumption and waste generation can be prevented. Moreover, energy is saved through the avoidance of drying steps. Up to now, however, carbon dioxide soluble dyes led to poor cotton dyeing. This work shows for the first time excellent dye fixation and coloration of the cotton after being dyed with specially synthesized fluorotriazinyl dyes in supercritical carbon dioxide. An industrial environmentally benign textile dyeing process can be expected in the near future, leading to substantial savings in water and dye consumption. Supercritical carbon dioxide can also be used as solvent for enzymatic oxidations. Because of its non-flammability, the oxidation in supercritical carbon dioxide is much safer than oxidations in conventional solvents. Another advantage is the high solubility of oxygen in supercritical carbon dioxide, resulting in high reaction rates. In this thesis, the lipoxygenase-catalyzed oxidation of linoleic acid in supercritical carbon dioxide is investigated. The oxidation reaction was found to occur in supercritical carbon dioxide without the need of any enzyme yielding a racemic mixture of the hydroperoxide isomers 9-(S)-hydroperoxydeca-10,12-dienoic acid and 13-(S)-hydroperoxydeca-9,11-dienoic acid. It is possible to use supercritical carbon dioxide as blowing agent for the foaming of polystyrene. Compared to the conventional process with pentane as blowing agent, the new process is inherently safer and greener, because problems with explosiveness and emissions are prevented. Large blocks of polystyrene can be produced because solidification is fast. In

Summary ___________________________________________________________________________

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this thesis, a multiple hole die has been designed and used, allowing the different strings to be melted together, producing larger sizes of polystyrene strings compared to the conventionally used single hole dies. Full scale implementation of supercritical foaming in the Netherlands would result in a pentane emission reduction of 2500 ton/year and a cost saving of 1.8 M€/year. Supercritical carbon dioxide is being applied commercially for the extraction of compounds from plants. A new application might be the extraction and separation of cannabinoids from cannabis for medical purposes e.g., as painkiller. Currently, hexane is used for extraction of the most common cannabinoids followed by silica gel column purification. However, cannabis contains a large number of other potentially biologically active cannabinoids that have never been isolated before. In this thesis, a process for the isolation of the major and minor cannabinoids is developed and tested. The decarboxylation reaction (needed prior to extraction) of the cannabinoic acids present in the plant was investigated first, and successfully tested in the pilot scale plant. Also, the supercritical extraction of the different cannabinoids was successfully carried out in the pilot plant. It is advantageous to combine supercritical carbon dioxide with ionic liquids as solvents for catalysis and separations. Recently, it has been discovered that the carbon dioxide pressure controls the miscibility of reactants, products, catalyst and ionic liquid, enabling fast atom-efficient reactions in a homogenous phase as well as instantaneous product recovery in a biphasic system. The ionic liquid/supercritical carbon dioxide technology was (partly) applied to four different types of chemical processes: (i) hydrogenation of methyl-(Z)-α-acetamidocinnamate, (ii) oxidation of benzylalcohol, (iii) nucleophilic substitution of 1-methyl-3-phenylpiperazine with 2-chloronicotinitrile, and (iv) hydrolysis of lignocellulosic biomass. All reactions could be carried out at high rate and selectivity in the homogeneous ionic liquid phase. In some cases, carbon dioxide was added in order to increase the reactant solubility. The catalysts could be reused without significant loss in activity or selectivity. The products were easily separated by addition of carbon dioxide as co-solvent in extractions, or addition of carbon dioxide as anti-solvent in precipitations. The quality of the products recovered from the carbon dioxide phase was high, because this phase was not contaminated by the ionic liquid or the catalyst. Common ionic liquids are synthesized from petrochemical resources. Instead, it would be more sustainable to use renewable resources. It is highly probable that naturally occurring ionic liquids exist. They remain liquid in times of water stress, so that the plant can survive periods of drought, saline and freezing conditions. Moreover, they allow water-insoluble metabolites present in the plant to be dissolved. Naturally occurring anions and cations were identified, and suggestions for naturally occurring ionic liquids and deep eutectic solvents were made. These natural solvents were able to dissolve several water-insoluble metabolites. Moreover, it was possible to carry out enzymatic reactions in these natural solvents. It was concluded that natural ionic liquids are a new class of cheap and green solvents with high potential for many processes.

Jaap van Spronsen

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Samenvatting Reacties en scheidingen in groene oplosmiddelen Oplosmiddelen worden gebruikt in de reactie- en scheidingsstap van chemische processen; om vaste stoffen op te lossen, om de viscositeit te verlagen, om temperaturen te reguleren, om producten terug te winnen door middel van extractie of kristallisatie, om reacties uit te voeren, en om schoon te maken. Aan het gebruik van oplosmiddelen zitten ecologische en economische bezwaren. In de Verenigde Staten wordt bijvoorbeeld 15-20 miljoen ton per jaar aan vluchtige organische oplosmiddelen uitgestoten door de chemische industrie. Deze organische oplosmiddelen worden gesynthetiseerd uit niet-duurzame bronnen als aardolie. Ideaal gezien zou men het liefst oplosmiddelenvrij werken, maar dat is niet altijd mogelijk. In plaats daarvan kan men alternatieve duurzame oplosmiddelen gebruiken, zoals water, superkritisch koolstofdioxide en ionische vloeistoffen. Het doel van dit proefschrift is de ontwikkeling van een aantal alternatieve processen gebaseerd op groene oplosmiddelen, en om aan te tonen dat dit zeer economisch en ecologisch interessant is. Water wordt gebruikt als een groen oplosmiddel bij de winning van soda en molybdaat uit afvalwater. Deze afvalwaterstroom uit de Rotterdamse haven (250 kton/jaar) wordt op dit moment geneutraliseerd met zwavelzuur en vervolgens geloosd op de Nieuwe Waterweg. In dit proefschrift wordt aangetoond dat dezelfde afvalwaterstroom niet langer met zwavelzuur behandeld hoeft te worden bij toepassing van eutectische vries kristallisatie, waarbij soda als waardevol bijproduct ontstaat. Dit proces is gedemonstreerd op locatie op proeffabriekschaal. Procesberekeningen tonen aan dat dit proces leidt tot een kostenbesparing van 2.1 M€ per jaar, en voordeliger wordt als de energieprijzen in de toekomst verder toenemen. Water kan vervangen worden door superkritisch koolstofdioxide bij het verven van katoen. Op dit moment wordt katoen (20 miljard kg/jaar) geverfd in water, waarbij 100 liter zuiver water per kg textiel wordt verbruikt en evenzoveel afvalwater verontreinigd met verfstoffen en zouten ontstaat. Deze afvalstroom kan worden voorkomen door het verfproces in superkritisch koolstofdioxide uit te voeren. Dit levert ook een energiebesparing op omdat een droogstap wordt vermeden. Tot nu toe is het niet gelukt katoen in superkritisch koolstofdioxide te verven. Hier wordt voor het eerst aangetoond dat katoen wel kan worden geverfd in superkritisch koolstofdioxide met speciaal ontworpen fluorotriazinyl verfstoffen, die een hoge fixatie en kleuring geven. Een industrieel verfproces wordt binnenkort verwacht. Superkritisch koolstofdioxide kan ook worden gebruikt als oplosmiddel voor enzymatische oxidaties. Oxidaties kunnen veiliger worden uitgevoerd in het niet-brandbare koolstofdioxide in vergelijking met conventionele brandbare oplosmiddelen. Een ander voordeel is de hoge oplosbaarheid van zuurstof in koolstofdioxide, wat resulteert in hoge reactiesnelheden. In dit proefschrift wordt de lipoxygenase-gekatalyseerde oxidatie van linolzuur in superkritisch koolstofdioxide onderzocht. De oxidatie blijkt zelfs plaats te kunnen vinden zonder aanwezigheid van het enzym, waarbij een racemisch mengsel van 9-(S)-hydroperoxydeca-10,12-dieenzuur and 13-(S)-hydroperoxydeca-9,11-dieenzuur ontstaat. Het is mogelijk om superkritische koolstofdioxide te gebruiken bij het schuimen van polystyreen. Vergeleken met het conventionele proces met pentaan als blaasmiddel is het nieuwe proces veiliger en schoner, omdat koolstofdioxide niet brandbaar is en pentaan emissies worden vermeden. Het is mogelijk grote blokken polystyreen te produceren door

Samenvatting ___________________________________________________________________________

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snelle stolling. In dit proefschrift wordt ook een nieuwe spuitmond met meerder openingen ontworpen, die het mogelijk maakt om meerdere strengen aan elkaar te smelten waardoor grotere dimensies kunnen worden verkregen in vergelijking met een enkele opening. Volledige vervanging van pentaan door superkritisch koolstofdioxide in Nederland levert een pentaan emissie reductie van 2500 ton per jaar en een kostenbesparing van 1.8 M€ per jaar op. Superkritisch koolstofdioxide wordt commercieel toegepast om waardevolle componenten uit planten te extraheren. Een nieuwe toepassingen is de extractie van cannabinoïden uit cannabis voor medische doeleinden, bijvoorbeeld als pijnstiller. Momenteel wordt hexaan gebruikt als extractiemiddel, gevolgd door kolomzuivering over silicagel. Cannabis bevat echter een groot aantal biologisch actieve cannabinoïden, die nooit eerder geïsoleerd zijn. In dit proefschrift wordt een proces voor de isolatie van verschillende cannabinoïden uit cannabis ontwikkeld en getest. Eerst werd de decarboxylatiereactie van de in de plant aanwezige zure cannabinoïden onderzocht, en succesvol toegepast op proeffabriekschaal. Op deze schaal werd ook de extractie van de verschillende cannabinoïden met behulp van superkritisch koolstofdioxide met succes uitgevoerd. Het combineren van superkritisch koolstofdioxide met ionische vloeistoffen als oplosmiddelen voor katalyse en scheidingen leidt tot nieuwe mogelijkheden. Het is recentelijk ontdekt dat de koolstofdioxide druk de mengbaarheid van reactanten, producten, katalysatoren en ionische vloeistof sterk bepaalt. Door variatie van druk is het mogelijk om reacties met hoge snelheid uit te voeren in een homogeen systeem, terwijl de scheiding plaatsvindt in een twee-fasen systeem. De ionische vloeistof/superkritisch koolstofdioxide technologie wordt toegepast of vier verschillende chemische processen: (i) hydrogenering van methyl-(Z)-α-acetamidocinnamaat, (ii) oxidatie van benzylalcohol, (iii) nucleofiele substitutie van 1-methyl-3-phenylpiperazine met 2-chloronicotinitril, en (iv) hydrolyse van lignocellulosische biomassa. Alle reacties konden in een homogene fase worden uitgevoerd met een hoge snelheid en selectiviteit. Soms werd koolstofdioxide toegevoegd ter verhoging van de oplosbaarheid van de reactanten. De katalysatoren konden worden hergebruikt zonder verlies aan activiteit en selectiviteit. De producten werden gemakkelijk geïsoleerd door middel van extractie of precipitatie met superkritisch koolstofdioxide. In de geïsoleerde producten kon geen vervuiling met de ionische vloeistof of katalysator aangetoond worden. De meest gebruikte ionische vloeistoffen worden gesynthetiseerd uit aardolieproducten. Het is veel duurzamer om hernieuwbare grondstoffen te gebruiken. Het is hoogst waarschijnlijk dat natuurlijke ionische vloeistoffen bestaan. Wanneer er te weinig water in een plant aanwezig is, onder andere door droogte, zout en vorst, zorgen de natuurlijke ionische vloeistoffen ervoor dat er een vloeibaar oplosmiddel aanwezig blijft, waardoor de plant kan overleven. Een andere functie van deze natuurlijke ionische vloeistoffen is het oplossen en transporteren van water-onoplosbare metabolieten. Natuurlijke anionen en kationen werden geïdentificeerd en gecombineerd ter verkrijging van natuurlijke ionische vloeistoffen en diep eutectische oplosmiddelen. Deze natuurlijke oplosmiddelen konden metabolieten oplossen. Ook werden hierin enzymatisch reacties uitgevoerd. Natuurlijk ionische vloeistoffen zijn een nieuwe klasse van goedkope en schone oplosmiddelen met groot potentiaal voor chemische processen.

Jaap van Spronsen

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Table of contents 1. Introduction ........................................................................................................................ 11

1.1 Problem definition.......................................................................................................... 11 1.2 Alternative ‘green’ solvents ........................................................................................... 12

1.2.1 Solvent-free processes............................................................................................. 12 1.2.2 Water ....................................................................................................................... 12 1.2.3 Supercritical carbon dioxide.................................................................................... 12 1.2.4 Ionic liquids............................................................................................................. 13

1.3 Scope of the thesis.......................................................................................................... 15 1.4 References ...................................................................................................................... 18

2. Eutectic freeze crystallization of soda and water ............................................................ 23

2.1 Introduction .................................................................................................................... 23 2.2 Eutectic freeze crystallization ........................................................................................ 25 2.3 Scraped cooled wall crystallizer..................................................................................... 27 2.4 Process development ...................................................................................................... 29 2.5 Experimental .................................................................................................................. 30 2.6 Results and discussion.................................................................................................... 31

2.6.1 Crystallizer performance ......................................................................................... 31 2.6.2 Process characteristics............................................................................................. 31

2.7 Economic evaluation ...................................................................................................... 35 2.8 Conclusions and outlook ................................................................................................ 37 2.9 References ...................................................................................................................... 38

3. Cotton dyeing using supercritical carbon dioxide........................................................... 43

3.1 Introduction .................................................................................................................... 43 3.2 Supercritical cotton dyeing............................................................................................. 45 3.3 Kinetics of the cotton dyeing reaction in supercritical CO2........................................... 47 3.4 Pretreatment methods for supercritical cotton dyeing.................................................... 51 3.5 Design and synthesis of better reactive dyes for supercritical cotton dyeing ................ 54 3.6 Economic evaluation ...................................................................................................... 58 3.7 Conclusions .................................................................................................................... 60 3.8 References ...................................................................................................................... 61

4. Oxidation of linoleic acid in supercritical carbon dioxide.............................................. 67

4.1 Introduction .................................................................................................................... 67 4.2 Experimental .................................................................................................................. 69

4.2.1 Materials.................................................................................................................. 69 4.2.2 Experimental set-up................................................................................................. 69 4.2.3 Experimental procedure .......................................................................................... 70

4.3 Results and discussion.................................................................................................... 71 4.4 Economic evaluation ...................................................................................................... 75 4.5 Conclusions .................................................................................................................... 76 4.6 References ...................................................................................................................... 77

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5. Foaming of polystyrene using supercritical carbon dioxide........................................... 81

5.1 Introduction .................................................................................................................... 81 5.2 Supercritical foaming of polystyrene ............................................................................. 83 5.3 Experimental ................................................................................................................. 85

5.3.1 Materials.................................................................................................................. 85 5.3.2 Extrusion system ..................................................................................................... 85 5.3.3 Dies.......................................................................................................................... 86 5.3.4 Experimental procedure .......................................................................................... 87

5.4 Results and discussion.................................................................................................... 88 5.5 Economic evaluation ...................................................................................................... 94 5.6 Conclusions .................................................................................................................... 96 5.7 References ...................................................................................................................... 97

6. Extraction of cannabinoids using supercritical carbon dioxide................................... 101

6.1 Introduction .................................................................................................................. 101 6.2 Decarboxylation of ∆9-THC acid ................................................................................ 103

6.2.1 Improvement of sample preparation and analysis................................................. 103 6.2.2 Decarboxylation reaction and kinetics .................................................................. 106

6.3 Solubility of ∆9-THC in supercritical CO2 .................................................................. 110 6.4 Supercritical extraction of cannabinoids from cannabis .............................................. 113 6.5 Economic evaluation .................................................................................................... 115 6.6 Conclusions .................................................................................................................. 116 6.7 References .................................................................................................................... 117

7. Catalysis and separations using ionic liquids and carbon dioxide............................... 121

7.1 Introduction .................................................................................................................. 121 7.2 Novel process for combining catalyzed reactions and separations using ionic liquids and CO2 .............................................................................................................................. 123 7.3 Synthesis of the ionic liquids ....................................................................................... 125

7.3.1 Synthesis of 1-butyl-3-methylimidazolium tetrafluoroborate............................... 125 7.3.2 Synthesis of 1-ethyl-3-methylimidazolium chloride............................................. 127 7.3.3 Synthesis of 1-methyl-3-(1H,1H,2H,2H-perfluorooctyl)imidazolium bistriflamide........................................................................................................................................ 127

7.4 Hydrogenation of methyl (Z)-α-acetamidocinnamate ................................................. 128 7.5 Oxidation of benzylalcohol .......................................................................................... 132 7.6 Nucleophilic substitution of 1-methyl-3-phenylpiperazine with 2-chloronicotinonitrile............................................................................................................................................ 134 7.7 Hydrolysis of lignocellulosic biomass ......................................................................... 136 7.8 Economic evaluation .................................................................................................... 140 7.9 Conclusions .................................................................................................................. 142 7.10 References .................................................................................................................. 143

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8. Naturally occurring ionic liquids .................................................................................... 151

8.1 Introduction .................................................................................................................. 151 8.2 Function of natural occurring ionic liquids .................................................................. 152 8.3 Synthesis of natural occurring ionic liquids and deep eutectic solvents ...................... 154 8.4 Dissolution of metabolites in naturally occurring ionic liquids ................................... 157 8.5 Enzymatic reactions in naturally occurring ionic liquids............................................. 159 8.6 Economic evaluation .................................................................................................... 161 8.7 Conclusions .................................................................................................................. 162 8.8 References .................................................................................................................... 163

9. Conclusions and recommendations ................................................................................ 169

Acknowledgements............................................................................................................... 171

Curriculum Vitae ................................................................................................................. 173

List of publications ............................................................................................................... 175

Patents ................................................................................................................................ 175 Journal articles.................................................................................................................... 175 Conference proceedings ..................................................................................................... 176

1 Introduction

By: J. van Spronsen and M. C. Kroon

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1. Introduction

1.1 Problem definition Most chemical processes use solvents in the reaction and the separation step. Solvents are necessary to dissolve solids, to lower the viscosity, to regulate temperatures, to recover compounds by means of extraction and crystallization, as reaction medium or for cleaning purposes1. Despite the fact that solvents are very useful for easy processing, their use is under considerable pressure. The use of large quantities of volatile organic compounds as solvents for chemical reactions and extractions, with a current worldwide cost estimated at € 6,000,000,000 per year2,3, is a major concern for today’s chemical processing industry. For instance, it is estimated that in the USA every year around 15-20 million ton of volatile organic compounds is discharged into the atmosphere as a result of industrial processing operations4, which accounts for 2/3 from all industrial emissions5.

Figure 1.1: Volatile Organic Compounds (VOC) emissions in the USA and Canada in the period 1990-2002

5

On the list of damaging chemicals, solvents rank highly, because they are volatile liquids that are difficult to contain1. The perceived effects of these solvents on human health, safety and the environment, combined with their volatility and flammability, is a strong incentive for minimizing their use, both for environmental and cost perspective. Minimizing solvent losses leads to avoiding the costs associated with disposal, legal liabilities and regulatory constraints. Therefore, the development of solvent-free processes as well as the development of environmentally benign new solvents, such as water, supercritical carbon dioxide and ionic liquids, has become a major issue. These alternative ‘green’ solvents may also lead to novel reactivity and improved performance of the separation process, resulting in economical as well as ecological advantages over the use of conventional solvents.

1. Introduction ___________________________________________________________________________

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1.2 Alternative ‘green’ solvents 1.2.1 Solvent-free processes Solvent-free processes are the best solution for minimizing solvent losses; the best solvent is no solvent (prevention instead of remediation). A reaction can be carried out without solvent when the reagents are liquids or when the reactive mixture can be melted to produce a liquid. In this case the excess reagent serves as solvent. For example, the production of chlorinated natural rubber has been carried out in excess liquid chlorine in order to eliminate the need for the usual carbon tetrachloride as solvent, which is difficult to remove from the product, chlorinated rubber2. Solvent-free separation steps include mechanical extraction instead of extraction with an organic solvent. Unfortunately, it is not always possible to work without solvent. In these cases less harmful solvents, which can easily be recovered, are desired. 1.2.2 Water Another solution to minimize and reduce the impact of solvent emissions is the use of water as a solvent. The use of water as reaction medium is often economically and environmentally attractive. Water is inexpensive and abundantly available. Moreover it is non-flammable and non-toxic, odorless and colorless and environmentally friendly. Water is especially interesting as solvent in biphasic industrial transition metal catalyzed reactions. The reactants and products form an organic phase and the catalyst and ligand are dissolved in the water phase. The reactants can react in the aqueous phase by the formation of a complex with the catalyst/ligand system. The formed products are not water-soluble and return to the organic phase. In this way water and catalyst can easily be separated from the product and recycled, minimizing the solvent losses2. The low mutual solubility of water and organic product leads to a reduced product contamination. The high polarity of water may lead to novel reactivity. However, the application of water as a green solvent is still limited due to the low solubility of organic substrates in water, which often leads to low reaction rates. Moreover, water is a protic coordinating solvent, so it can react with organometallic complexes. Therefore, water cannot be used as solvent for all catalytic reactions and often modifications of catalysts and ligands are necessary2. Another case where water is not an ideal solvent is the dyeing of cotton where undesirable side reactions with water degrade the dyestuff2. 1.2.3 Supercritical carbon dioxide Supercritical carbon dioxide is also a good candidate for replacing volatile organic compounds as solvents for reactions and separations6-9. Carbon dioxide is non-toxic, non-flammable, relatively inert, abundant and inexpensive6. It is a supercritical fluid at temperatures higher than 304.2 K (= 31.1 oC) and pressures higher than 7.38 MPa (= 73.8 bar). Under these conditions the distinction between the gas phase and liquid phase is nonexistent, and carbon dioxide can only be described as a fluid. This can be explained by looking at the phase diagram of carbon dioxide (see Figure 1.2). The boiling line separates the vapor and liquid region and ends in the critical point. At any point on the boiling line below

1. Introduction ___________________________________________________________________________

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its critical temperature and pressure, carbon dioxide exists as a liquid with vapor above it. As the temperature is raised, the liquid density falls due to expansion, whereas the gas density rises due the pressure increase. Eventually, at the critical point, the densities become identical and the distinction between liquid and gas disappears6.

Figure 1.2: Phase diagram of carbon dioxide

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In the supercritical region, the density of carbon dioxide can be varied by changing the temperature and/or pressure. Supercritical carbon dioxide has properties between those of gases and liquids. It has the ability to diffuse through materials like a gas, and to dissolve organic compounds like a non-polar liquid (resembling hexane). By adjusting the pressure of the supercritical carbon dioxide, the solvent properties can be adjusted to be more ‘gas-like’ (low solvency power) or ‘liquid-like’ (high solvency power), which makes it a highly tunable solvent. The low critical temperature allows heat-sensitive materials to be processed without damage. The fact that not all chemical substances are soluble in supercritical carbon dioxide permits selective extraction. When the pressure is relieved after an extraction step, the carbon dioxide evaporates and pure product without any remaining carbon dioxide is obtained. Therefore, supercritical extraction is often used as solvent for foods and medicines, for which it eliminates the possibility of leaving toxic residues of organic solvents6-9. However, the use of supercritical carbon dioxide as green solvent has some limitations. It is not a very good solvent for many (polar) substances. Moreover, it has to be used under pressure. This may lead to higher operating and equipment costs6. 1.2.4 Ionic liquids During the last fifteen years, ambient temperature ionic liquids were recognized as a new class of environmentally benign solvents11-24. Ambient temperature ionic liquids are molten salts that are liquid at room temperature. They resemble high-temperature molten metallic salts, but contain at least one organic ion that is relatively large and asymmetric compared to a metallic ion. Therefore, the attractive forces between the positively charged ions (cations) and the negatively charged ions (anions) of an ionic liquid can be kept so far apart that crystallization is hindered and that the resulting substance is a totally ionic (non-aqueous) liquid at room temperature11,12. Most common cations and anions are shown in Figure 1.3. It is estimated that there are approximately one trillion (1018) accessible ionic liquids13.

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Common cations:

N+

R1

R3 R2

R4N

+

R2R1

NN+

R1 R2

Ammonium Imidazolium Pyrrolidinium

P+

R1

R3 R2

R4N

+

R

C+

N

N NR6

R5

R2R1

R4

R3

Pyridinium Phosphonium Guanidinium

Common anions:

Halides: Cl-, Br-, I- Phosphates: PF6-

Sulfates: CH3OSO3- Borates: BF4

-

Sulfonates: CF3SO3- Imides: N(CF3SO2)2

-

Acetates: CF3CO2- Cyanates: N(CN)2

-

Figure 1.3: Most common cations and anions

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Ionic liquids are considered to be green solvents, because they have negligible vapor pressure at room temperature14. As a result, ionic liquids are odorless. They do not evaporate, even when exposed to vacuum, and most of them do not combust, even when exposed to an open flame. The fact that ionic liquids are non-volatile and non-flammable makes them safer and more environmentally benign solvents than the traditional volatile organic solvents11,14. Other properties of ionic liquids are inherent to salts in the liquid state and include the wide liquid temperature range allowing tremendous kinetic control in reactions, the good thermal stability, the high ionic conductivity and the wide electrochemical window representing the high electrochemical stability of ionic liquids against oxidation or reduction reactions15. Furthermore, ionic liquids have very good solvency power for both organic and inorganic materials, polar and non-polar, which makes them suitable for catalysis16-22. It is possible to tune the physical and chemical properties of ionic liquids by varying the nature of the anions and cations. In this way, ionic liquids can be made task-specific for a certain application11. The use of ionic liquids as solvents for reactions and separations may offer a solution to both the solvent emission and the catalyst-recycling problem16. Ionic liquids allow atom-efficient reactions to be carried out at high rates and selectivities, because they are able to dissolve a wide range of catalysts16-21. Moreover, it is possible to extract organic compounds from ionic liquids with supercritical carbon dioxide without any contamination by the ionic liquid and without any solvent losses, because ionic liquids do not dissolve in carbon dioxide22-24. In this way, no energy-intensive distillation step is required.

1. Introduction ___________________________________________________________________________

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1.3 Scope of the thesis This thesis aims to solve the problem of volatile organic compounds as solvents by replacing them with alternative ‘green’ solvents for several applications in the chemical industry. The environmentally benign solvents investigated in this thesis are water (chapter 2), supercritical carbon dioxide (chapters 3 to 7) and ionic liquids (chapters 7 and 8). In all cases, their use does not only lead to savings in solvent losses, but also leads to novel reactivity and/or improved performance of the chemical process, resulting in economical as well as ecological advantages over the use of conventional solvents. Chapter 2 focuses on the separation of soda from molybdate containing waste water streams. In this case water is used as a solvent for soda. The waste water stream is conventionally treated with sulfuric acid in order to neutralize the stream, followed by adsorption of sodium molybdate on an ion exchange column, and the resulting sodium sulfate solution is discarded into the environment. Here, an alternative method for separating soda and water is investigated. In this so-called ‘eutectic freeze crystallization’ process the soda and water are both crystallized and purely obtained, without the need of any sulfuric acid. No waste water is produced, and the soda can be sold as valuable by-product. A skid-mounted pilot plant is completely designed, built and tested at Afval Verwerking Rijnmond (AVR), resulting in a positive benefit of 2.1 M€/year compared to the conventional process. In chapter 3 the dyeing of cotton by using supercritical carbon dioxide as alternative solvent is investigated. Conventionally, cotton is dyed using large amounts of water, which ends as a chemical waste containing hydrolyzed dye, salts and alkali. In this work, supercritical carbon dioxide has been used as a solvent instead, eliminating the production of huge amounts of waste water. Moreover, the textiles do not need to be dried after dyeing, saving a lot of energy. However, most common carbon dioxide soluble dyes lead to poor cotton dyeing results. On basis of a kinetics study, two methods to increase the dyeability of cotton in supercritical carbon dioxide are investigated: (i) the use of a pretreatment method to overcome the inaccessibility of the cotton sites, and (ii) the use of more reactive dyes. This chapter shows for the first time excellent dye fixation and coloration of the cotton after being dyed with fluorotriazinyl dyes in supercritical carbon dioxide. An industrial environmentally benign textile dyeing process can be expected in the near future, leading to substantial savings in water and dye consumption. Chapter 4 focuses on the use of supercritical carbon dioxide as solvent for enzymatic reactions. Specifically, the enzymatic oxidation of the water-insoluble linoleic acid by lipoxygenase in supercritical carbon dioxide is investigated. This reaction is conventionally carried out in water, but the rate of reaction is very low due to the low solubility of oxygen, resulting in mass transfer limitations. In this work, supercritical carbon dioxide was found to be able to dissolve the oxygen well, thereby significantly enhancing the rate of reaction. However, it was found that the enzyme did not have any function, because no selectivity towards the preferred isomer was found. Instead, a 50:50 mixture of 2 isomers was produced, which only happens in the absence of the enzyme. Therefore, the oxidation reaction in supercritical carbon dioxide was in fact non-catalytic. Although the supercritical carbon dioxide does not seem to be a good solvent for the enzymatic oxidation, it is still a promising solvent for intrinsically safe large-scale chemical oxidations, without any problems with flammability and/or explosiveness.

1. Introduction ___________________________________________________________________________

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Supercritical carbon dioxide is also used as environmentally benign solvent in chapter 5 for the foaming of polystyrene. Compared to the conventional process with pentane as blowing agent, the new process is inherently safer and ‘greener’ because problems with explosiveness and emissions are prevented. Moreover, it is no longer necessary to store the foam for at least four weeks in order to remove all blowing agent, because the carbon dioxide directly evaporates after pressure release. Large blocks of polystyrene can be produced because solidification is fast. In this chapter a specially designed multiple hole die is used, where the different strings are melted together, producing larger sizes of polystyrene strings compared to the conventionally used single hole dies. Full scale implementation of supercritical foaming in the Netherlands would result in a pentane emission reduction of 2500 ton/year and a cost saving of 1.8 M€/year. In chapter 6 the solvent supercritical carbon dioxide is used as extraction medium for the extraction of cannabinoids from cannabis. Only the most well-known cannabinoids have been isolated previously by extraction with the volatile organic solvent hexane. However, cannabis contains a large number of other potentially biologically active cannabinoids that have never been isolated before. In chapter 6 a process for the isolation of the major and minor cannabinoids from cannabis in their pure form is developed. First, the decarboxylation reaction of the carboxylic acids present in the plant into their biologically active forms is investigated. Thereafter, the separation of the different cannabinoids is at the center of interest. Supercritical carbon dioxide is used to dissolve the cannabinoids and to extract them from the cannabis material. Advantages are the absence of flammability or toxicity issues, the simple and efficient solvent removal, and the well-controlled extract quality. Moreover, the supercritical extraction is scaled up to pilot scale level. The economic impact of the new process for the production of cannabinoids is negligible because of the small market. However, the newly developed process is a good example for introducing environmentally benign processes using supercritical carbon dioxide into the pharmaceutical industry. Two green solvents i.e., ionic liquids and supercritical carbon dioxide, are used as catalysis and separation media in chapter 7. The combination of these two solvents in chemical processing can be a feasible alternative for the wasteful and energy-intensive conventional production processes. Combining catalysis and separations using ionic liquids and carbon dioxide leads to considerable process intensification when the miscibility windows phenomenon is applied. Using this phenomenon, it is possible to carry out reactions in a homogeneous phase, whereas the separation takes place in the biphasic system, where the products are recovered from the phase that does not contain any ionic liquid. Advantages of this new process set-up are the high reaction and separation rates, the low waste generation and energy consumption, the high product quality and the safe working conditions. Moreover, it can lead to significant economical and environmental benefits. Since the principle of miscibility windows is a general phenomenon, it is likely that the new process set-up is applicable to many industrial processes. The ionic liquid/supercritical carbon dioxide technology was (partly) applied to four different types of chemical processes: (i) hydrogenation of methyl-(Z)-α-acetamidocinnamate, (ii) oxidation of benzylalcohol, (iii) nucleophilic substitution of 1-methyl-3-phenylpiperazine with 2-chloronicotinitrile, and (iv) hydrolysis of lignocellulosic biomass. All reactions could be carried out at high rate and selectivity in the homogeneous ionic liquid phase. The quality of the products recovered from the supercritical carbon dioxide phase was high, because it was not contaminated by the ionic liquid or the catalyst.

1. Introduction ___________________________________________________________________________

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Ionic liquids can have a hidden environmental cost in their synthesis. Therefore, chapter 8 focuses on naturally occurring ionic liquids that do not have any problems with toxicity or biodegradability. It is highly probable that naturally occurring ionic liquids alternative to water exist. They remain liquid in times of water stress, so that the plant can survive periods of drought, saline and freezing conditions. Moreover, they allow water-insoluble metabolites present in the plant to be dissolved. Suggestions for naturally occurring ionic liquids and deep eutectic solvents were made on basis of identification of naturally occurring anions and cations. These natural solvents were found to be able to dissolve several water-insoluble metabolites. Moreover, it was possible to carry out enzymatic reactions in these natural solvents. It was concluded that natural ionic liquids are a new class of cheap and green solvents with high potential for many processes. Finally, in chapter 9 an outlook on the future potential of alternative ‘green’ solvents is presented. Recommendations and challenges for future applications of water, supercritical carbon dioxide and ionic liquids as solvents are given.

1. Introduction ___________________________________________________________________________

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1.4 References

1. Reichardt, C. Solvents and solvent effects in organic chemistry; 3rd Ed.; Wiley-VCH Verlag: Weinheim, Germany, 2003.

2. Matlack, A.S., Introduction to Green Chemistry, Marcel Dekker, Inc.: New York

(NY), USA, 2001.

3. Seddon, K. R.; Ionic Liquids for Clean Technology, J. Chem. Tech. Biotechnol. 1997, 68 (4), 351-356.

4. Allen, D. T.; Shonnard, D. R.; Green Engineering, Prentice Hall: Upper Saddle River

(NJ), USA, 2002.

5. EPA and Environmental Canada, Volatile Organic Compounds (VOC) emissions in the USA and Canada in the period 1990-2002, http://www.ec.gc.ca/pdb/can_us/2004 CanUs/section3_e.html.

6. Jessop, P. G.; Leitner, W., Eds. Chemical Synthesis Using Supercritical Fluids; Wiley-

VCH Verlag: Weinheim, Germany, 1999.

7. Beckman, E. J.; Supercritical and Near-Critical CO2 in Green Chemical Synthesis and Processing, J. Supercrit. Fluids 2003, 28 (2-3), 121-191.

8. Leitner, W.; Supercritical Carbon Dioxide as a Green Reaction Medium for Catalysis,

Acc. Chem. Res. 2002, 35 (9), 746-756.

9. Sheldon, R. A.; Green Solvents for Sustainable Organic Synthesis: State of the Art, Green Chem. 2005, 7 (5), 267-278.

10. Poling, B. E.; Prausnitz, J. M.; O’Connell, J. P. The Properties of Gases and Liquids,

5th ed., McGraw-Hill: New York (NY), USA, 2001.

11. Wasserscheid, P.; Welton, T., Eds. Ionic Liquids in Synthesis; Wiley-VHC Verlag: Weinheim, Germany, 2003.

12. Earle, M. J.; Seddon, K. R.; Ionic Liquids. Green Solvents for the Future, Pure Appl.

Chem. 2000, 72 (7), 1391-1398.

13. Holbrey, J. D.; Seddon, K. R.; Ionic Liquids, Clean Products & Processes 1999, 1

(4), 223-236.

14. Earle, M. J.; Esperança, J. M. S. S.; Gilea, M. A.; Lopes, J. N. C.; Rebelo, L. P. N.; Magee, J. W.; Seddon, K. R.; Widegren, J. A.; The Distillation and Volatility of Ionic Liquids, Nature 2006, 439 (7078), 831-834.

15. McEwen, A. B.; Ngo, H. L.; LeCompte, K.; Goldman, J. L.; Electrochemical

Properties of Imidazolium Salt Electrolytes for Electrochemical Capacitor Applications, J. Electrochem. Soc. 1999, 146 (5), 1687-1695.

1. Introduction ___________________________________________________________________________

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16. Olivier-Bourbigou, H.; Magna, L.; Ionic Liquids: Perspectives for Organic and Catalytic Reactions, J. Mol. Cat. A 2002, 182-183, 419-437.

17. Welton, T.; Ionic Liquids in Catalysis, Coordination Chem. Rev. 2004, 248 (21-24),

2459-2477.

18. Dyson, P. J.; Transition Metal Chemistry in Ionic Liquids, Transition Metal Chem. 2002, 27 (4), 353-358.

19. Sheldon, R. A.; Lau, R. M.; Sorgedrager, M. J.; Van Rantwijk, F.; Seddon, K. R.;

Biocatalysis in Ionic Liquids, Green Chem. 2002, 4 (2), 147-151.

20. Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S. M. S.; Chemical and Biochemical Transformations in Ionic Liquids, Tetrahedron 2005, 61 (5), 1015-1060.

21. Muzart, J.; Ionic Liquids as Solvents for Catalyzed Oxidations of Organic

Compounds, Adv. Synth. Catal. 2006, 348 (3), 275-295.

22. Brennecke, J. F.; Maginn, E. J.; Ionic Liquids: Innovative Fluids for Chemical Processing, AIChE J. 2001, 47 (11), 2384-2389.

23. Blanchard, L. A.; Hancu, D.; Beckman, E. J.; Brennecke, J. F.; Green Processing

Using Ionic Liquids and CO2, Nature 1999, 399 (6731), 28-29.

24. Blanchard, L. A.; Brennecke, J. F.; Recovery of Organic Products from Ionic Liquids Using Supercritical Carbon Dioxide, Ind. Eng. Chem. Res. 2001, 40 (1), 287-292.

2 Eutectic freeze crystallization of soda and

water By: J. van Spronsen, M. Rodriguez Pascual, F. E. Genceli, D. O. Trambitas, H. Evers and G. J. Witkamp

___________________________________________________________________________

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2. Eutectic freeze crystallization of soda and water

2.1 Introduction One of the common petrochemical industrial waste streams is a dilute aqueous stream containing carbonate, bicarbonate and various trace impurities. Such streams are normally acid treated to neutralize the carbonates, and are disposed after further purification. An example of such a waste stream is the incinerator stream from Afval Verwerking Rijnmond (AVR) industries1. The current treatment of this incinerator stream starts by neutralization with sulfuric acid followed by adsorption of sodium molybdate on an ion exchange column. The resulting sodium sulfate solution is discarded into the environment and the molybdenum is recovered as a concentrated sodium molybdate solution by desorption with caustic. In Figure 2.1 a schematic overview of the AVR process is depicted.

Figure 2.1: Treatment of blow down at AVR

AVR’s blow down stream consists of water (93 w%), sodium molybdate (NaMoO4, 1000 ppm), sodium carbonate (soda, Na2CO3, 3-4%), and sodium bicarbonate (NaHCO3, 3-4%). The total volume of this blow down stream is 750 ton/day. In the neutralization step, the following chemical reactions take place: Na2CO3 + H2SO4 → Na2SO4 + H2O + CO2 (Eq. 2.1) 2 NaHCO3 + H2SO4 → Na2SO4 + 2 H2O + 2 CO2 (Eq. 2.2) Therefore, a daily amount of around 40 ton sulfuric acid is needed, which is equal to a truck load sulfuric acid per day (Figure 2.2).

Figure 2.2: The daily truck load of sulfuric acid at AVR

Neutralization

Blow down

co2

acid

Column purification

Neutral Blowdown

base

Molybdate solution

Waste water

2. Eutectic freeze crystallization of soda and water ___________________________________________________________________________

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An alternative approach to process this stream is by using a technique named eutectic freeze crystallization (EFC) developed by TUDelft2. This technique operates as follows on the AVR process stream. The AVR stream is cooled down and the ice, soda (as decahydrate) and sodium bicarbonate will crystallize from the solution. Due to the difference in density between salt, ice and mother liquor, ice floats to the top and salt settles at the bottom of the crystallizer. The unit operations of crystallization and separation are thus combined in one piece of equipment. The impurities (sodium molybdate) present at ppm levels in the feed stream can be recovered more easily from the bleed stream after concentration by the EFC process, and can be sold as such (Figure 2.3). The advantages of EFC over the current treatment are that acid dosage is no longer required, and that pure ice and carbonate salts are obtained as valuable products.

Figure 2.3: EFC of the AVR blow down stream

Advantages over the AVR process are:

• No sulfuric acid necessary for neutralization • No license needed for storage and handling of sulfuric acid • No need for molybdate recovery by column purification • No waste water; the ice produced can be recycled into the process • Soda and sodium bicarbonate are products that can be sold

In this chapter the recovery of carbonate salts from an aqueous solution containing soda, sodium bicarbonate and trace impurities by a continuous EFC process is described. The performance of a scaled-up version of a new type of EFC crystallizer under realistic process conditions at AVR industries is reported.

Concentrated Molybdate solution

Ice

Soda and/or sodium bicarbonate

Blow down cooling


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2.2 Eutectic freeze crystallization Eutectic freeze crystallization (EFC) is a technique to simultaneously crystallize salts and water (Figure 2.4). It has been applied for purification of aqueous streams containing sodium chloride3-5, copper sulfate6, potassium nitrate7, and magnesium sulfate8,9.

Figure 2.4: Simultaneous crystallization and gravitational separation of ice (top) and salt crystals (bottom) formed by EFC

Here, a stream consisting of water, soda and sodium bicarbonate is studied. EFC of this ternary system is explained on basis of the phase diagram10,11, which is shown in Figure 2.5. The three eutectic solubility lines in this ternary phase diagram projected along the temperature axis, represent the conditions where two solid phases are in equilibrium with the solution. The eutectic temperature of sodium bicarbonate, ice and pure sodium bicarbonate solution lies at -2.23 oC, the eutectic temperature of soda decahydrate, ice and pure soda solution at -2.1 oC. The third three-phase line of solid sodium bicarbonate, solid soda decahydrate in a soda - sodium bicarbonate containing solution is depicted from -3.318 oC to 20 oC. The three eutectic phase lines meet in the quadruple point at -3.318 oC, where sodium bicarbonate, soda decahydrate, ice and a solution containing sodium bicarbonate + soda are in equilibrium. In a batch EFC process, the AVR industrial solution is first cooled down from point A producing ice, and after trespassing the metastable region (point B) soda is produced. Because the heat of crystallization is released and supersaturation is consumed, the solution composition and temperature will go to a point close to the soda + ice solubility line (point C). Upon further decrease in temperature the solution composition closely follows the soda + ice solubility line (line 1). As long as no sodium bicarbonate is formed, the crystallization of only soda can be continued within the metastable zone of the sodium bicarbonate (point D). By working in this region the production of soda and ice can be increased substantially. However, when the metastable region is trespassed (point E) the sodium bicarbonate starts to crystallize as well, and the solution approaches the quadruple point. Then, a mixture of sodium bicarbonate and soda settles with a low filterability and low added value. A batch EFC is thus not industrially feasible. Instead, it is possible to only produce the desired pure soda (as decahydrate) when operating in a continuous mode. This can be depicted in Figure 2.4 as a single point of operation instead of a trajectory through the phase diagram.


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Figure 2.5: Projected ternary phase diagram of sodium bicarbonate, soda and water with the three eutectic solubility lines (straight) and the two metastable solubility lines (dashed)

In continuous operation, it is possible to work in the metastable region of sodium bicarbonate (point D), because the sodium bicarbonate does not yet crystallize and the soda yield is the highest. Working in the metastable region includes a risk because of the potential crystallization of sodium bicarbonate, but this risk can be controlled. If the solution starts to become milky due to the formation of sodium bicarbonate crystals the feed flow is increased without stopping the continuous process. By increasing the feed flow the concentration of sodium bicarbonate decreases and the total composition returns to point C where only soda and ice are produced. Once the sodium bicarbonate has been washed out of the system via the salt outlet, the process can be brought back to the maximum production point D. For streams rich in sodium bicarbonate EFC can be performed at a point on the sodium bicarbonate + ice solubility line resulting in the crystallization of sodium bicarbonate and ice11.


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2.3 Scraped cooled wall crystallizer Important criteria for the design of an EFC crystallizer are a high heat transfer rate, a low torsion force on the shaft exerted by the scrapers and stable operation over a prolonged period of time. The total heat transfer rules the production rate and should be as high as possible to keep the installation sufficiently small. In-line measurement of torque and heat transfer rate during the process indicate if a not removable ice scale layer starts to form on the heat exchanging surface. This allows remaining in a safe operating region under the selected process conditions. A prototype of a suitable scraped cooled wall crystallizer was built in Delft by Rodriguez Pascual et al.12 A scaled up version of this crystallizer was needed to achieve the high production rates of ice and soda from the industrial AVR stream11 (Figure 2.6 and 2.7). The prototype can easily be scaled up by stacking more heat exchanger modules on top of each other. By doing this the necessary torque to drive the scrapers and the size of the crystallizer remain acceptable. In our case two heat exchanger modules sufficed, each consisting of two vertical concentric cylinders that are scraped from both sides. This crystallizer has a volume of 180 liter and an outside wall made of transparent polymethylmethacrylate (PMMA) with a total heat exchanger surface area of 0.76 m2.

Figure 2.6: Scaled up version of the scraped cooled wall crystallizer with two heat exchanger modules


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In this scaled up version the gravitational ice and salt separation is also not hampered due to the sufficiently large gap between the heat exchanger cylinders. The gap between the heat exchanger modules allows the radial separation of ice and salt crystals, which facilitates their gravitational separation. It also improves mixing in the middle section of the crystallizer and flattens the radial temperature profile. To better control the prevention of ice scaling the temperature of the inner and outer cylinder can be controlled independently. Based upon experience with previous models much attention was paid to the unhampered transport of ice from the crystallizer6,9. At the top of the crystallizer a conically shaped plastic cylinder is fixed to the rotating shaft. This cone directs the ice layer at the top part of the crystallizer towards the exit pipe. The conical shape of the bottom of the crystallizer prevents building up of salt at the bottom.

Figure 2.7: Scraped cooled wall crystallizer at AVR


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2.4 Process development The flow sheet of the transportable pilot plant is presented in Figure 2.8. The incinerator stream, or so-called blow down stream, enters a 500 liter buffer tank, from which the carbonate containing solution is pumped into the crystallizer with a membrane pump. For all other process streams Watson Marlow peristaltic pumps are used because of their high accuracy, reliability and good performance with slurries. The flow rates of the process streams and of the cooling liquid are measured with an accuracy of ±0.25 l.h-1 by magnetic flow transmitters manufactured by Rosemount Fisher. Before entering the crystallizer the solution is pre-cooled in a plate heat exchanger from Alfa Laval with a 6.6 m2 surface area. The cooling machine has a 10 kW cooling capacity at 0 oC, uses freezium (43% potassium formiate in water) as a coolant and was supplied by Tamson Instruments B.V. The temperature of the cooling liquid was controlled with an accuracy of 0.1-0.5%. The temperatures of all streams as well as the temperature within the crystallizer and in the separator are measured with an accuracy of ±0.01oC by PT-100 sensors connected to an ASL F250 precision thermometer with a resolution of ±0.001oC. The separator has a volume of 120 liter. The belt filters for the salt and the ice were supplied by Larox-Pannevis and have a surface area of 0.75 m2 and 2.25 m2 respectively. In order to prevent cold losses into the environment all equipment is well isolated. For automatic data acquisition a Rosemount Delta-V system was used11.

Figure 2.8: Flow sheet of the pilot used at AVR


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2.5 Experimental A picture of the transportable EFC skid is shown in Figure 2.9. The total skid was transported from TU Delft to AVR industries at Rozenburg. The operation of the EFC skid was filmed at AVR13.

Figure 2.9: EFC skid

Under continuous operation the buffer tank is fed with the blow down stream, with the recycled filtrate and with the wash liquor from the belt filters. The flow from the buffer tank to the crystallizer is cooled to a temperature close to the operating temperature in the crystallizer. The slurry in the crystallizer is cooled by the heat flux through the vertical heat exchangers. The overflow of the crystallizer consists of ice slurry with minor amounts of the salt and is pumped to the separator. The overflow of the separator consisting of ice slurry is pumped to the ice belt filter. On the belt filter the ice is filtered and washed with cold water. The bottom flow of the crystallizer is combined with the bottom flow from the separator and pumped to the salt belt filter. On this filter the salt, that depending on the operating temperature is either soda decahydrate or a mixture of soda decahydrate and sodium bicarbonate, is filtered and washed with a saturated soda solution. The spent wash solution was kept apart and not recycled into the process. After each residence time samples were taken from all process streams. Ice slurry samples taken before the belt filter were filtered over a cooled glass filter, and part of the ice crystals were washed with cold water. Salt slurries before the belt filter were filtered over a glass filter, and part of the salt crystals was washed with saturated soda solution. Ice/salt slurries samples from the middle of the crystallizer were separated in a cooled separation funnel and filtered to measure the salt, ice and solution percentages. The samples were analyzed by ICP- AES and by ion chromatography. The carbonate-bicarbonate content of salt, ice and solutions were determined by titration. Scanning electron microscope pictures of the soda decahydrate, sodium bicarbonate and mixed product were taken.


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2.6 Results and discussion 2.6.1 Crystallizer performance The main limitation on the heat transfer rate of a scraped cooled wall crystallizer is the maximum temperature difference that can be applied between the cooling plates and the solution before excessive ice scaling occurs. The maximum temperature difference between solution and heat exchanger surface without the formation of an ice scaling layer on the heat exchanger mainly depends on the type and concentration of the ions in solution, and is difficult to predict even for pure systems14,15. The presence of a non-crystallizing solute can affect the water activity and consequently the freezing point of ice, having a positive effect on the maximum temperature difference that can be applied. In this case the non-crystallizing sodium bicarbonate helps to achieve a higher temperature difference. A preliminary EFC experiment showed that at a temperature difference of 8oC and a heat transfer rate of 7.0 kW.m-2 over 3 hours run time, the torque on the axis of the crystallizer increased above the upper limit of 200 N.m. So for the experiments at AVR a temperature difference of 6oC was chosen, resulting in a heat transfer rate of 5.0 kW.m-2. The heat transfer rate was calculated from the temperature difference over the cooling plates and the coolant flow through the cooling plates. For all experiments at AVR (run time up to 10 hours) the torque on the crystallizer axis and the heat transfer rate indicated that no excessive scaling took place. A heat transfer of 5.0 kW.m-2 was maintained in the experiments. 2.6.2 Process characteristics

Two types of experiments were carried out, one where ice and soda decahydrate were produced and a second type where ice, and a mixture of soda decahydrate and sodium bicarbonate were produced. The blow down stream from AVR entered the buffer tank at 35 l.h-1 with a concentration of about 4 wt% Na2CO3 and 4 wt% NaHCO3. The solution from the buffer tank was fed into the crystallizer at 200 l.h-1 and because of the recycling of process streams the concentration in the buffer tank was higher than that of the blow down stream. The residence time of the feed solution in the crystallizer was 1.0 hour and the production rate was 30 kg.h-1 for ice and 2.5 kg.h-1 for salt in both experiments. The operating conditions during soda decahydrate production are given in Table 2.1. The crystallizer temperature during operation of experiment 2 is shown in Figure 2.10.


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Table 2.1: Experimental operating conditions

Experiment no. 1 2

Crystallizer (200 liter): Flow from buffer vessel (l.h-1) 200 200 Temperature (oC) -3.8 -3.8 Heat transfer rate (kW.m-2) 5.0 5.0 Bottom flow to salt belt filter (l.h-1) 50 50 Overflow to separator (l.h-1) 150 150 Residence time (min) 60 60 Ice production rate (kg.h-1) 30 30 Salt production rate (kg.h-1) 2.5 2.5 Separator (120 liter): Flow from crystallizer (l.h-1) 150 150 Bottom flow to salt belt filter (l.h-1) 60 60 Overflow to ice belt filter (l.h-1) 90 90 Temperature (oC) -3.8 -3.8 Residence time (min) 48 48 Process in: Blow down flow into buffer (l.h-1) 35 35 Ice wash water flow (l.h-1) 3.0 3.0 Process out: Bleed stream (l.h-1) 16 16 Ice from belt filter (kg.h-1) 22 22 Salt from belt filter (kg.h-1) 1.5 2.0 Salt wash liquid flow (l.h-1) 2.0 2.0 Overall: Run time (min) 300 300 Salt product (kg) 5.8 6.7 Soda (%) 37.0 36.7 Sodium bicarbonate (%) 0.8 0.2 Molybdenum (ppm) 13 64

Figure 2.10: Temperature in the crystallizer during operation


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The blow down stream from AVR mainly contains Na2CO3 and NaHCO3 with concentrations fluctuating between 3-4 wt% and 3-4 wt% respectively, and because of these variations a real steady state operation does not exist. Table 2.2 presents the average concentrations of the blow down, feed and crystallizer solutions after 5 residence times of two experiments where only soda decahydrate was produced. Table 2.2: Na2CO3 and NaHCO3 concentrations in the process solutions

Na2CO3 (wt%) NaHCO3 (wt%)

Blow down stream 4.1 4.1 Feed solution 4.2 5.5

Experiment 1:

Crystallizer solution 4.3 5.5 Blow down stream 4.6 4.4 Feed solution 4.4 5.8

Experiment 2:

Crystallizer solution 5.0 5.7 In both cases the temperature in the crystallizer was kept at -3.8oC with an average solid content of 15 wt% (1.26 wt% Na2CO3⋅10H2O and 14 wt% ice) in the crystallizer. The crystallizer thus operates within the metastable sodium bicarbonate region. The purity of the salt product was 99% with less than 1% of sodium bicarbonate. In the pilot plant the mother liquid was apparently not sufficiently washed out on the belt filters, which explained the high molybdenum content found in the salt after drying (Table 2.1). The same product washed in situ on a more accurate lab scale equipment showed that the uptake of molybdenum in soda crystals was below 1 ppm. Scanning electron microscope (SEM) pictures of the soda decahydrate product are shown in Figure 2.11. The ice product after washing was sufficiently pure to be recycled into the plant.

Figure 2.11: Pure Na2CO3⋅10H2O product after washing


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If the temperature in the crystallizer was decreased to -4.0oC, the bicarbonate started to crystallize, and the system approached the quadruple point. The NaHCO3 crystals are needles that fill up the voids between the large Na2CO3⋅10H2O crystals, resulting in poor filtration properties. The product from the belt filter as shown in Figure 2.12 consisted of 17 w% NaHCO3 and 50 w% Na2CO3⋅10H2O with 25 wt% mother liquid that contained 350 ppm molybdenum. In Figure 2.12 the washed soda crystals are partially dissolved, while the sodium bicarbonate needles kept their shape.

Figure 2.12: Mixture of the Na2CO3⋅10H2O and NaHCO3 after the belt filter

To avoid simultaneous crystallization of both salts the feed stream can be increased until point C in Figure 2.5 is reached as explained before, and sodium bicarbonate is washed out of the crystallizer.


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2.7 Economic evaluation The newly designed EFC process for treatment of the AVR blow down stream (Figure 2.1) is economically compared to the conventional AVR treatment (Figure 2.3). In the conventional AVR process, 40 ton of sulfuric acid per day is required to neutralize the blow down stream. Also, a small amount of sodium hydroxide (in the order of 0.4 ton per day) is needed for the column purification of the sodium molybdate, but this is negligible in the economic analysis. The formed sodium sulfate solution is discharged into the environment and requires cost for licensing. Also, 18 ton CO2 per day is produced and emitted into the atmosphere, for which emission rights have to be purchased. A third license for handling of sulfuric acid is required. Only the concentrated molybdate solution (in the order of 0.7 ton per day on a molybdate basis) is sold as a valuable side product, but this is also produced in the alternative EFC process and will not be taken into account in the economical analysis. Instead, the EFC process only requires cooling for the production of 720 ton ice per day. This results in a value of 26 MWh (95 GJ) per day using a melting enthalpy of ice of 334 kJ.kg-1 and assuming a coefficient of performance (COP) value of 2.5. Energy costs for the EFC treatment thus seem substantially higher compared to the conventional AVR process. However, no chemicals (sulfuric acid, sodium hydroxide), no column purification equipment, and no licenses (discharging CO2, discharging sodium sulfate, sulfuric acid handling) have to be purchased. Moreover, 43 ton soda (on an anhydrous basis) per day, 720 ton water per day and concentrated molybdate solution (in the order of 0.7 ton per day) are obtained as a valuable products. The energy saved by not having to produce this soda already exceeds the total energy input of this EFC process. Table 2.3 shows the prices of the resources for the current process and the future EFC process. The main differences in variable costs for the conventional process and the new EFC process are presented in Table 2.4. Table 2.3: Prices of resources in the conventional and the new EFC process for the AVR blow down treatment

Resources Price Ref.

Sulfuric acid 100 €/ton 16 Soda (anhydrous) 105 €/ton 17 CO2 emission rights 13 €/ton 18 Water 1.5 €/ton 19 Electricity 0.05 €/kWh 20 As can be seen from Table 2.4, the EFC process is economically more attractive compared to the conventional process, and leads to a positive balance of 2.1 M€/year. Reason is that more valuable products are obtained using the EFC process. At higher energy prices the advantage of EFC will be greater because the energy savings for not producing soda via the conventional Solvay process outweigh the energy input of the EFC process. Table 2.4 does not take into account the differences in fixed costs. The fixed costs of the conventional process include costs for licenses for sulfuric acid handling and discharge of sodium sulfate solution, and costs for an additional purification column. All these fixed costs


- 36 -

are absent in the new EFC process, which makes it even more economically attractive. However, an extra EFC plant needs to be constructed. Even though this may not be more expensive than the purification column, the investment still has to be made, and this can be a barrier for adoption of the new EFC process. Table 2.4: Main differences in variable costs of the conventional blow down stream treatment at AVR and the new EFC process

Amount

per day

Costs/benefits

(k€/year)

Sulfuric acid consumption (ton) 40 - 973 CO2 emission rights (ton) 18 - 85

Conventional process

Total - 1058

Energy consumption (MWh) 26 - 482 Soda production (ton) 43 + 1099 Water production (ton) 720 + 394

EFC process

Total + 1011


- 37 -

2.8 Conclusions and outlook Eutectic Freeze Crystallization (EFC) of soda + sodium bicarbonate containing industrial waste streams is a promising new technology. The scaled up version of a scraped cooled wall crystallizer was successfully tested at Afval Verwerking Rijnmond (AVR) in a skid-mounted pilot plant that was connected to the soda containing blow down stream. The heat transfer inside the crystallizer was maintained at 5.0 kW.m-2. The in-line torque and heat transfer measurements in the crystallizer were effective in detecting early ice scale formation on the cooling surface of the heat exchangers leading to efficient control of the ice scraping process. The ice product after washing was sufficiently pure to be recycled into the plant. Operating at -3.8oC within the metastable sodium bicarbonate zone resulted in soda decahydrate as the sole product with good filtration properties and a low molybdenum content. If the temperature was decreased to -4.0oC, the sodium bicarbonate started to crystallize, and the system approached the quadruple point. In this case, the mixed soda-sodium bicarbonate product had poor filtration properties due to a bimodal size distribution resulting in a high molybdenum content. The EFC process results in a positive benefit of 2.1 M€/year compared to the conventional AVR process. Moreover, the EFC process is more environmentally benign due to the absence of any sodium sulfate and carbon dioxide emissions. Because the AVR blow down stream contains a mixture of soda and sodium bicarbonate, an improved EFC process can be designed by adding an extra (conventional) crystallizer. In the first (EFC) crystallizer, soda is produced in the metastable zone of sodium bicarbonate. After filtration of the soda and ice, the sodium bicarbonate is crystallized from the solution in the second (conventional) crystallizer. The sodium bicarbonate is filtered off, and the resulting mother liquid (with the eutectic concentration of soda + sodium bicarbonate) is recycled back into the first (EFC) crystallizer. In this way, both pure soda and sodium bicarbonate can be produced. Another way to improve the EFC process is the production of soda as a single product, without any sodium bicarbonate production. Soda will be the sole product if carbon dioxide is stripped from the blow down solution at higher temperatures. This can be done in an additional stripping column. The sodium bicarbonate is then decomposed into soda and CO2: 2NaHCO3 → CO2 (g) + Na2CO3 + H2O (Eq. 2.3) Sodium bicarbonate will be the sole product (without any soda) when the blow down stream is treated with CO2. This can also be performed in a carbonation column with CO2 injection. The soda is then transformed into sodium bicarbonate: CO2 + Na2CO3 + H2O → 2NaHCO3 (Eq. 2.4) In the last option, an EFC unit is no longer needed, because sodium bicarbonate has a lower solubility in water than soda, and crystallizes above the freezing point of water. An additional advantage is that the large energy consumption of the EFC process is circumvented, and the benefits remain the same.


- 38 -

2.9 References

1. Afval verwerking Rijnmond (AVR), http://www.vangansewinkel.eu/nl/ 2. Witkamp, G. J.; Van Spronsen, J.; Hasselaar, M.; Treatment of Molybdate Containing

Waste Streams, International Patent WO 2008/115063 A1 (2008). 3. Stepakoff, G. L.; Siegelman, D.; Johnson, R.; Gibson, W.; Development of an Eutectic

Freezing Process for Brine Disposal, Desalination 1974, 14, 25-38. 4. Barduhn, A. J.; Manudhane, A.; Temperature Required for Eutectic Freezing of

Natural Waters, Desalination 1979, 28, 233-241. 5. Swenne, D. A.; Thoenes, D.; The Eutectic Freeze Crystallization of Sodium Chloride

Dihydrate and Ice, J. Separation Process Technol. 1985, 6, 17-25. 6. Van der Ham, F.; Seckler, M. M.; Witkamp, G. J.; Eutectic Freeze Crystallization in a

New Apparatus: The Cooled Disk Column Crystallizer. Chem. Eng. Proc. 2003, 43

(2), 161-167. 7. Vaessen, R. J. C.; Seckler, M. M.; Witkamp, G. J.; Eutectic Freeze Crystallization

with an Aqueous KNO3-HNO3 Solution in a 100-liter Cooled Disc Column Crystallizer, Ind. Eng. Chem. Res. 2003, 42 (20), 4874-4880.

8. Himawan, C.; Kramer, H. J. M.; Witkamp, G. J.; Study on the Recovery of Purified

MgSO4.7H2O Crystals from Industrial Solution by Eutectic Freeze Crystallization, Separation Purification Technol. 2006, 50 (2), 240-248.

9. Genceli, F.E.; Gärtner, R.; Witkamp, G. J.; Eutectic Freeze Crystallization in a 2nd

Generation Cooled Disk Column Crystallizer for MgSO4-H2O System, J. Crystal

Growth 2005, 275 (1-2), e1369-e1372. 10. Rodriguez Pascual, M.; Trambitas, D.; Saez Calvo, E.; Kramer, H.; Witkamp, G. J.;

Determination of the Eutectic Solubility Lines of the Ternary System NaHCO3–Na2CO3–H2O, Accepted for publication in Chem. Eng. Res. Design 2009.

11. Van Spronsen, J.; Rodriguez Pascual, M.; Genceli, F. E.; Trambitas, D. O.; Evers, H.;

Witkamp, G. J.; Eutectic Freeze Crystallization from the Ternary Na2CO3-NaHCO3-H2O System: A Novel Scraped Wall Crystallizer for the Recovery of Soda from an Industrial Aqueous Stream, Accepted for publication in Chem. Eng. Res. Design 2009.

12. Rodriguez Pascual, M.; Genceli, F. E.; Trambitas, D. O.; Evers, H.; Van Spronsen, J.;

Witkamp, G. J., A Novel Scraped Cooled Wall Crystallizer: Recovery of Sodium Carbonate and Ice from an Industrial Aqueous Solution by Eutectic Freeze Crystallization, Accepted for publication in Chem. Eng. Res. Design 2009.

13. Eutectic Freeze Crystallization (EFC): A Film about a New Technology Developed at

the TU Delft, http://www.new-energy.tv.


- 39 -

14. P. Pronk, P.; Infante Ferreira, C. A.; Witkamp, G. J.; Influence of Solute Type and Concentration on Ice Scaling in Fluidized Bed Ice Crystallizers; Chem. Eng. Sci. 2006, 61 (13), 4354-4362.

15. Vaessen, R. J. C.; Himawan, C.; Witkamp, G. J.; Scale Formation of Ice from

Electrolyte Solutions on a Scraped Surface Heat Exchanger Plate, J. Crystal Growth 2002, 237-239 (3), 2172-2177.

16. Sulfuric acid market prices 2008: http://www.purchasing.com/article/225589-Sulfuric

_acid_prices_explode.php

17. Soda market prices 2008: http://www.the-innovation-group.com/ChemProfiles/Soda% 20Ash.htm

18. CO2 emission rights price 2009: http://zakelijk.eneco.nl/Energievandaag/Nieuwsover-

zicht/ Pages/AlleogengerichtopmarktCO2-emissierechten.aspx

19. Water market price 2009: http://www.verswater.nl/Water+is+goedkoop/De_prijs_van _kraanwater.htm

20. Electricity market prize 2008: http://www.essent.nl/content/thuis/producten/stroom_en

_gas/stroom_gas_vast/tarieven_stroom_vast_3jaar_10k.jsp

3 Cotton dyeing using supercritical carbon

dioxide By: J. van Spronsen, M. V. Fernandez Cid, M. van der Kraan, W. J. T. Veugelers, G. F. Woerlee, G. J. Witkamp

and K. N. Gerstner

___________________________________________________________________________

- 43 -

3. Cotton dyeing using supercritical carbon dioxide

3.1 Introduction Cotton consists for more than 90% of cellulose1. Cellulose is a biopolymer consisting of a linear chain of several hundred to over ten thousand β(1→4) linked D-glucose units. Figure 3.1 shows the chemical structure of cotton.

Figure 3.1: Chemical structure of cotton1

Traditional dyeing of cotton requires large amounts of water, nearly 100 kg of water per kg of cotton2. Because the worldwide production of cotton is around 10 million ton per year, this means that the waste water production from cotton dyeing alone is already as much as 1 billion ton per year2. At the end of the dyeing process, this water contains about 0.1 million ton of hydrolyzed dye, 16 million ton of salt, and 5 million ton of alkali3. The high levels of salts and alkali are the result of cotton dyeing with reactive dyes, making the stream a heavily polluted chemical waste that is difficult to treat. The chemical reaction during the dyeing process is a nucleophilic substitution reaction between the dye molecule (dye-Cl) and one of the hydroxyl-groups of the cotton (R-OH): R-OH + dye-Cl + NaOH → RO-dye + H2O + NaCl (Eq. 3.1) The reaction products are dyed cotton and sodium chloride. An example of a commercially available reactive dye is depicted in Figure 3.2. Figure 3.2: Chemical structure of reactive red 13 dye

N

N

OH NH

N

N

N

Cl

Cl

NaO3S SO3Na

O

HH

H

O

OH

H OH

H

OH

O

O

HH

H

OH

H OH

H

OH

O. .

3. Cotton dyeing using supercritical carbon dioxide ___________________________________________________________________________

- 44 -

Dyeing

Water

Dye

Soda

Cotton

Washing

Drying

Water

Heat

Dyed cotton

Waste water

Up to 40% of the reactive dye applied is hydrolyzed during the dyeing process due to competitive reaction with hydroxyl anion nucleophiles3,4: dye-Cl + NaOH → dye-OH + NaCl (Eq. 3.2) The high affinity of the hydrolyzed dye molecules for the cotton requires an extensive wash-off after dyeing consuming water and energy4. Furthermore, the scarcity of water in the near future puts a boundary to the textile industry and requires looking for alternative processes to improve the dyeability of cotton with reactive dyes5-7. There is great need for a more ecological dyeing process. In Figure 3.3 a schematic overview of the conventional cotton dyeing process is shown. Figure 3.3: Schematic overview of conventional cotton dyeing using water as solvent


- 45 -

Dyeing & washing

CO2

Dye

Cotton

Dyed cotton

CO2 recovery

Unreacted dye

3.2 Supercritical cotton dyeing In order to reduce the waste production and energy consumption, the last two decades research has been carried out to develop a more sustainable water-free process for dyeing textiles8-10. As a result, supercritical carbon dioxide (CO2) has been chosen as a potential dye solvent instead of water, eliminating the production of huge amounts of waste water from cotton dyeing. Other benefits of supercritical CO2 include its green properties (non-flammable, relative non-toxic and inert), the higher diffusion rate and the lower viscosity compared to water11-13, thus enhancing mass transfer phenomena. Consequently, the dye penetration into the fibers is facilitated reducing dyeing times14. Since no water is used, the textiles do not need to be dried after dyeing, saving a lot of energy4. As the dye molecules cannot be hydrolyzed, no additional waste is created3,4. Moreover, the remaining unreacted dye and supercritical CO2 can be easily separated by simply lowering the pressure3. Figure 3.4 shows the potential process for cotton dyeing in supercritical CO2 as solvent. Figure 3.4: Schematic overview of a potential process for cotton dyeing using supercritical CO2 as solvent

Synthetic fibers, such as polyester, have been successfully dyed in supercritical CO2 at laboratory scale14-16. However, it has not been possible yet to dye cotton. Problem is that the conventionally used dyes are insoluble in supercritical CO2

17. Since 35% of the world share market is represented by cotton2, development of a method for dyeing cotton is vital. Therefore, dyes were synthesized that are soluble in supercritical CO2

17-23. A typical example is shown in Figure 3.517. As can be seen from Figure 3.5, this molecule does not contain any sodium sulfonate groups, rendering a non-polar dye. Figure 3.5: Chemical structure of a CO2-soluble reactive dye

17

N

N N

N O

N

N

N

Cl

Cl


- 46 -

The dyeing reaction in supercritical CO2 is shown below. It can be noticed that no base is present to capture the acidic hydrochloric acid, resulting in a low reaction rate. R-OH + dye-Cl → RO-dye + HCl (Eq. 3.3) The first experiments of cotton dyeing with CO2 soluble dyes were not successful. Even after ten years of intensive research the process still gave very poor dyeing results17-23. In the best case, the temperature needed for dyeing was as high as 160oC, resulting in severe cotton damage24. Furthermore, the dyeing results were far below commercially acceptable. Several studies were done to improve the dyeability of cotton in supercritical CO2

20-23. Often the improvements made use of extra chemicals or extra process steps that made the process less ecological and commercially unviable as well. It can be concluded that supercritical cotton dyeing is potentially interesting, but not yet possible. The aim of this study was to investigate the kinetics of the dyeing reaction in order to better understand the problems related to the dyeing process in supercritical CO2

25. Methanol was suggested as a model for cotton by Bentley et al.26, because the reactive site of the cotton is also a primary alcohol. Two problems were identified based on the results of the kinetics study: (i) inaccessibility of the cotton sites for reaction, and (ii) low reactivity of the dyes. The inaccessibility of the cotton is caused by the fact that cotton is a hydrophilic fiber with large crystalline regions, whereas supercritical CO2 is a non-polar solvent. Therefore, the CO2 cannot penetrate deeply into the cotton fibers. A possible solution for this problem is the use of an appropriate pretreatment method, opening up the fibers and increasing the accessibility of the dyeing sites27. The low reactivity of the dyes is caused by the absence of any base in the supercritical CO2 (Eq. 3.3). In conventional water-based cotton dyeing, the reaction is catalyzed by the base. In order to overcome this problem, new dyes were synthesized with a higher reactivity so that the basic catalyst is no longer needed3,28,29. Another solution to this problem is the application of acidic catalysts instead of basic catalysts30. An advantage is that acidic catalysts are soluble in supercritical CO2, whereas basic catalysts simply react with CO2 or are insoluble.


- 47 -

3.3 Kinetics of the cotton dyeing reaction in supercritical CO2 The kinetics of the dyeing reaction in supercritical CO2 (with/without phosphoric acid added) and in pure methanol (for comparison) were studied experimentally25. Methanol was also used as model for cotton26. Three different non-polar dyes were synthesized and tested. The CO2 was bought from HoekLoos and had a purity of 99.97%. The methanol used was HPLC grade from Acros. The structures of the non-polar reactive dyes are shown in Figure 3.6. The dichlorotriazinyl dye, abbreviated to RCl2, and the monochlorotriazinyl derivate, coded as RCl-OCH3, were supplied by a well-known dye manufacturer. The other monochlorotriazinyl dye, abbreviated to RCl-NHCH3, was synthesized in the laboratory.

Figure 3.6: Structures of the three dyes abbreviated by RCl2, RCl-OCH3 and RCl-NHCH3

RCl-NHCH3 was synthesized from RCl2 in the following way: The dichlorotriazinyl dye, RCl2, (100 mg, 0.217 mmol) was dissolved in a mixture of dioxane (100 ml) and water (20 ml). Methylamine was added into the solution until a pH of 10.7 was reached. TLC analysis of the reaction mixture indicated that the reaction was complete. The pH of the solution was adjusted to 7.5 was hydrochloric acid (1 N, 7 ml). Over 30 minutes water (210 ml) was added to the reaction mixture. The resulting crystal slurry was stirred for 1 hour at room temperature. The precipitate was filtered, washed with dioxane + water (1:2.5, 10 ml) and dried under vacuum over phosphorus pentoxide. Yield: 90 mg (91%), purple powder; TLC analysis showed one product spot (RF = 0.7; acetone:hexane = 2:3), MS m/z 455 (M+). 1H-NRM in DMSO: δ 8.4-7.7 (m, 7H), 3.6 (q, 4H), 2.5 (s, 3H), 1.3 (t, 6H).

N

N

N

O

O N

CH3

CH3

N

N

N

Cl

Cl

N

N

N

O

O N

CH3

CH3

N

N

N

Cl

NH

CH3

NH2 CH3

N

N

N

O

O N

CH3

CH3

N

N

N

Cl

O

CH3

CH3 OH

RCL 2

RClOCH 3 RClNCH 3

(RCl2)

(RCl-OCH3) (RCl-NHCH3)


- 48 -

A high-pressure batch reactor was used to carry out the kinetics experiments in supercritical conditions. The reactor, designed for operating up to 350 bar, consists of a 150 ml pressure vessel connected to a pressure manometer and a needle valve (Figure 3.7).

Figure 3.7: Reactor used in the kinetics experiments

To carry out the kinetic experiments, first a stock solution of 0.2 g/l of the dyes in acetonitrile was made. This solution was subsequently, diluted to a concentration of 0.02 g/l with methanol and immediately used for the reactions. When supercritical carbon dioxide (CO2) was the reaction medium, 1 ml of the dye solution in methanol was introduced in the reactor. Once the reactor was sealed, 90 g of liquid carbon dioxide was introduced from the CO2 bottle to the reactor via the needle valve. The reactor is, subsequently, placed in the thermostatic bath settled at a temperature of 120°C. Within 10 minutes the pressure in the reactor reached 300 bar. For the experiments with phosphoric acid, 0.01 g H3PO4 per g methanol was added to the dye solution. Conversely, when the kinetic experiments were performed in methanol as reactant and as a solvent medium, 25 ml of the dye solution in methanol was poured into the reactor. The reactor was sealed and placed in the thermostatic bath at 120°C. For both procedures, when the reaction time was completed, the reactor was removed from the thermostatic bath and the reaction was stopped by cooling. Afterwards, the reaction mixture was carefully collected in a sample flask via the needle valve. The composition of the sample was immediately determined by HPLC analysis. The chromatographic analyses were performed with a Chrompack liquid chromatograph with an (250mm x 4.6 mm) Inertsil 5 ODS-2 column and using 85 v% acetonitrile and 15 v% water as mobile phase at a flow rate of 1 ml/min. Samples of 20 µl were injected with a Marathon autosampler and the chromatographic column was maintained at 295 K. The dye samples were detected at their maximum absorption wavelength (513 nm) with a Varian ProStart 310UV/VIS Detector. The results of the kinetics experiments are shown in Table 3.1. The first rate reaction rate constant, k, was calculated from the conversion versus time plot using3,25:

[ ] [ ] )(lnln 0101ttkRClRCl tt −−= (Eq. 3.4)

where [RCl]t is the concentration of the dye at time t.


- 49 -

Table 3.1: Rate constant (k) for the reaction of the 3 dyes with methanol as a function of the solvent (supercritical carbon dioxide, acidified (0.004 mol% H3PO4) supercritical carbon dioxide, and methanol) at 120

oC

Dye 105 x k (s

-1)

Methanol CO2 CO2 + H3PO4

RCl2 47 12 11 RCl-OCH3 2.0 0.5 27 RCl-NHCH3 0.3 6.3 21 Generally, the reactivity of dichlorotriazinyl dyes in water is higher than the reactivity of monochlorotriazinyl dyes in water31. It can be noticed from Table 3.1 that this trend is indeed observed when the reaction takes place in methanol: k(RCl2) > k(RCl-OCH3) > k(RCl-NHCH3). This difference in reactivity is less pronounced in supercritical CO2 as a solvent. However, under acidic conditions in supercritical CO2 an inversion in reactivity is observed, showing that the monochlorotriazinyl dyes have a higher reactivity compared to the dichlorotriazinyl dyes: k(RCl-OCH3) > k(RCl-NHCH3) > k(RCl2). Moreover, the addition of phosphoric acid to supercritical CO2 enhances the reaction rate for the monochlorotriazinyl dyes, but does not have any effect on the reactivity of the dichlorotriazinyl dye25. These effects can be explained in the following way: Under basic and neutral conditions the reaction proceeds by nucleophilic attack of the methanol on the dye32,33. In this case, the inductive effect of the substituents is rate determining: δ+(Cl2) > δ+(ClOCH3) > δ+(ClNCH3). In Figure 3.8 shows the charge distribution over the dye molecule. Figure 3.8: Charge distribution of the dichlorotriazinyl ring

Under acidic conditions the reaction proceeds by protonation of the nitrogen atom in the ring of the dye molecule. Protonation leads to an increase in reactivity, because the protonated ring is stabilized by a mesomeric effect (-OCH3 and –NHCH3 groups have a strong mesomeric effect), as shown in Figure 3.9. The mesomeric effect dominates the inductive effect, and therefore the monochlorotriazinyl dyes have a higher reactivity in acidic media32.

N N

NR

Cl

Cl

δ+

δ-

δ+

δ-


- 50 -

Figure 3.9: Mesomeric effect of the protonated triazinyl ring

Based on these results, it is expected that monochlorotriazinyl dyes perform better than dichlorotriazinyl dyes for the dyeing of cotton in supercritical CO2. Until now, only dichlorotriazinyl dyes have been investigated in literature. It is suggested to use monochlorotriazinyl dyes instead in this research. Also, it was observed that the addition of acid improves the reaction rate. Therefore, acid will be added in future studies3,25,27-30. Another way to increase the reactivity of the triazinyl dye is to replace the chlorine atom(s) by fluorine atom(s)31. This was observed before in conventional water-based cotton dyeing, and will be tested for supercritical dyeing as well3,28,29. A final method to improve reactivity is to increase the rate of transport of the dye towards to reactive site of the cotton. This is a physical barrier instead of a chemical barrier, and does not follow from the kinetics study. It is suggested to use a pretreatment method to improve the accessibility of the dyeing sites of the cotton27. Reason is that cotton swells when conventionally dyed in water because of a decrease in glass transition temperature of the cotton34, which does not occur in supercritical CO2 cotton dyeing. It is expected that the addition of a solvent in a pretreatment step will result in swelling of the cotton, and therefore increasing the availability of reactive sites when the cotton is supercritically dyed in the next step. Results are presented in the next paragraph.

R

N

C

N+

N

C

Cl

O

CH3

H

R

N

C

N

N

C

Cl

O+

CH3

H


- 51 -

3.4 Pretreatment methods for supercritical cotton dyeing The use of auxiliary solvents (water, dimethylsulfoxide, acetone, methanol, and ethanol) to facilitate the dissolution and transportation of the dye to the cotton is investigated in this paragraph. Cotton pretreatment with solvent is expected to increase the reactivity of the dye, because the cotton swells and reactive sites become available27,34. The dichlorotriazinyl dye (RCl2, Figure 3.6) was used to dye cotton in combination with a pretreatment step. Mercerized cotton (128 g/m2) was purchased from Stork B.V. Acetone and Ethanol (analytical grade) were supplied from J. T. Baker. Methanol (HPLC grade) was obtained from Fischer and dimethylsulfoxide (analytical grade) was purchased from Acros. The carbon dioxide was delivered by HoekLoos with a purity of 99.97%. In a sample flask a piece of 10 g of cotton was immersed in a fluid medium with a ratio of (50:1) ml/g cotton. The pretreatment was carried out at 313 K and 0.1 MPa by constantly shaking the sample flask for 12 h. The pretreated piece of cotton was removed from the fluid medium and transferred as such to the reactor for the dyeing procedure. Approximately 60% by weight of the cotton substrate of the fluid medium remained in the fabric. Protic solvents (i.e., ethanol, methanol and water) and aprotic solvents (i.e., dimethylsulfoxide and acetone) were studied as fluid medium. The dyeing equipment used in these experiments consists of a 4 liter autoclave with a heating jacket. A schematic representation of the cotton dyeing equipment in supercritical carbon dioxide can be seen in Figure 3.10, and Figure 3.11 shows a picture of the equipment. Figure 3.10: Schematic representation of the cotton dyeing equipment

The dyeing vessel was preheated by oil at 393 K for two hours before dyeing. 1% on weight of the fiber of dye was used for each experiment. At this dye concentration no damage of the cotton fibers was observed. When dye powder was used, this was placed at the bottom of the autoclave in the dye holder between two filter plates. When dye was dissolved beforehand in a solvent, or mixture of solvents, the dye solution was added to the top of the autoclave immediately before closing it. The same procedure was followed when extra co-solvent was applied in the dyeing tests. The pretreated cotton (10 g) was removed from the fluid medium (the pretreatment solvent), and immediately placed in the autoclave. The autoclave was sealed and CO2 was pumped into the dyeing vessel. When the pressure reached 18.0 MPa, the

dye powder

circulation pump

CO2 supply pump

autoclave with heating jacket

textiles

heater

oil pump


- 52 -

circulation pump was started (begin of dyeing time).The supercritical carbon dioxide was circulated through the vessel at a flow rate of 110 l/h. The CO2 supply was stopped when the pressure reached 20.0 MPa. The temperature increased from 316 K to 380 K in the course of the dyeing and the pressure to 25.0 MPa. After 120 minutes (unless mentioned otherwise) the pressure was released and the cotton removed from the autoclave. A portion of each piece of dyed cotton was used for extraction to determine the dye fixation. To determine the fixation of the dye in the piece of cotton, a Soxhlet extraction was carried out until no more dye came out from the cotton. A portion of the each piece of dyed cotton was extracted for 1 hour in a 15:35 (v/v) mixture of water and acetone at 358 K.

Fig 3.11: Cotton dyeing reactor used in the pretreatment experiments

The performance of each pretreatment solvent was determined by measuring two response variables27,35:

- Color strength:

The Kubelka-Munk equation was used to determine the color intensity of the dyed pieces of cotton before and after extraction:

min

2min

R2

)R1(

S

K

⋅

−= (Eq. 3.5)

where K is the absorbance, S is the scattering, and Rmin is the minimum of the spectrophoto-metrically measured reflectance curve of the cotton35. The spectrophotometer used was SpectroCam 75RE (spectral range: 380-750nm; illumination source: pulsed Xenon gas discharged tube; ISO standard geometry:


- 53 -

Annular 45°/0°; measurement averaging: 35 measurements per second). A commercial acceptable value for the K/S (after extraction) is 10-20 (-).

- Dye fixation:

The dye fixation (i.e., the percentage of dye molecules that reacted with the cotton) was determined by comparison of the color intensity (K/S) after dyeing and after extraction using35:

%100)S/K(

)S/K(F

dyed

extracted ⋅= (Eq. 3.6)

The results for both color strength (before and after extraction) and dye fixation using different pretreatment solvents are shown in Table 3.2. Table 3.2: K/S and fixation as function of pretreatment solvent

Pretreatment (K/S)dyed

(-)

(K/S)extracted

(-)

Fix (%)

No pretreatment <0.1 <0.1 <1 Water 0.4 0.2 56 Dimethylsulfoxide 30 0.3 1 Acetone 2 0.2 10 Methanol 5 3 60 Ethanol 3 0.8 30 From Table 3.2 it can be concluded that only pretreatment with methanol significantly improves the color strength of the end product (after extraction). The other solvents, either protic or aprotic, do not have a positive effect under these conditions. It can be noticed that the color strength of the cotton with dimethylsulfoxide as pretreatment solvent before extraction is high, but after extraction no dye is chemically attached to the cotton. There is no fixation of the dye. This can be explained by the fact that the dye dissolves in the dimethylsulfoxide, and the dimethylsulfoxide remains dissolved in the cotton during the dyeing process without any reaction with the cotton. The dimethylsulfoxide prefers the cotton phase over the CO2 phase, and remains in the cotton after CO2 removal. However, after extraction with acetone/water, all dimethylsolfxide with dissolved dye is washed away. The other pretreatment solvents have a much greater affinity for CO2. During the dyeing reaction, the pretreatment solvent including dye dissolve into the CO2 phase, and are removed with the CO2, rendering a low color strength product.


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N

N NH

N

N

N

F

F

N

N NH

N

N

N

OCH3

F

N

N NH

N

N

N

F

NH2

N

N NH2+

N

N

N

F

F

F

ammonia

MeOH

SF2

SFNH2

SFOCH3

3.5 Design and synthesis of better reactive dyes for supercritical cotton

dyeing From the kinetics25 and the pretreatment27 experiments, it was concluded that the currently available reactive dyes were unsuitable for supercritical cotton dyeing. The reactivity in combination with the solubility of the dyes in supercritical CO2 was too low. It was observed, however, that addition of acid and methanol enhanced the dyeing reaction27. From conventional cotton dyeing in water, it is known that the highest reactivity is achieved with difluorotriazinyl-based reactive dyes31,34. The fixation of these dyes is low due to the competing hydrolysis reaction. Therefore, dichlorotriazinyl dyes are conventionally used instead. In supercritical CO2, there is no problem with hydrolysis, because there is no water present. This led to the idea to use difluorotriazinyl-based reactive dyes in supercritical CO2 in order to increase the reactivity3,28-30. The most simple dye (with the smallest molecular weight, and therefore the highest solubility in CO2) was chosen. Based on the kinetics studies in which an inversion of reactivity between the monochloro- en dichloro-substituted dyes was observed in CO2 + acid25, also monofluorotriazinyl reactive dyes are studied. In total three new dyes were synthesized according to the scheme below (Figure 3.12)3,28-30. Figure 3.12: Synthesis of fluorotrianizyl reactive dyes

(RF2)

(RF-OCH3)

(RF-NH2)


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Synthesis of RF2 reactive dye:

4-Phenylazoaniline (7.89 g, 40 mmol) was dissolved in a mixture of dioxane (400 ml) and water (200 ml). The solution was cooled to 0 °C. Cyanuric fluoride (3.41 ml, 40 mmol) was added dropwise over 20 minutes keeping the temperature at 0 °C and the pH of the reaction mixture at 4-4.5 with sodiumcarbonate (2M). The resulting crystal slurry was stirred for 20 minutes at 0 °C followed by 1 hour stirring at 20 °C. The precipitate was filtered, washed with water (100 ml) and dried under vacuum over phosphoruspentoxide. Yield, 8.7 g (70 %), yellow powder; TLC analysis showed one product spot (Rf =0.53; acetone:hexane=1:2, Polygram® Sil G/UV254 as adsorbent phase), MS m/z 312 (M+). Synthesis of RF-OCH3 reactive dye:

RF2 (500 mg, 1.6 mmol) was suspended in a mixture of methanol (50 ml) and anhydrous sodiumcarbonate (150 mg, 1.4 mmol). After 1 hour stirring at room temperature, TLC analysis showed the reaction to be complete. Over 5 minutes water (100 ml) was added. The resulting product slurry was stirred for an additional 5 minutes. The precipitate was filtered of, washed with water and dried under vacuum over phosphoruspentoxide. Yield, 450 mg (87 %), yellow powder; TLC analysis showed one product spot (Rf = 0,4; acetone:hexane=1:3, Polygram® Sil G/UV254 as adsorbent phase), MS m/z 324 (M+) Synthesis of RF-NH2 reactive dye:

RF2 (1 g, 3.2 mmol) was dissolved in dioxane (70 ml). Ammonia (2.5%, 10 ml) was added, resulting in immediate precipitation of the product. After 5 minutes stirring at room temperature, TLC analysis showed the reaction to be complete. Over 10 minutes water (140 ml) was added. The resulting product slurry was stirred for an additional 5 minutes. The precipitate was filtered of, washed with water and dried under vacuum over phosphoruspentoxide. Yield, 0.9 g (91%), yellow powder; TLC analysis showed one product spot (Rf = 0.55; acetone:hexane=2:3, Polygram® Sil G/UV254 as adsorbent phase), MS m/z 309 (M+). Synthesis of RCl2 and RCl-NH2 reactive dyes (for comparison):

4-Phenylazoaniline (7.89 g, 40 mmol) was dissolved in a mixture of dioxane (480 ml) and water (160 ml). The solution was cooled to 0°C. A solution of cyanuric chloride (7.52 g, 40 mmol) in dioxane (40 ml) was added drop wise over 1 hour, while keeping the temperature at 0°C and the pH of the reaction mixture at 6-7 with sodium carbonate (2M, 12,5 ml). TLC analysis of the reaction mixture indicated that the reaction was completed. Over 1 hour a mixture of dioxane (560 ml) and water (800 ml) was added to the reaction mixture at 0°C. The resulting crystal slurry was stirred for 1 hour at 20°C. The precipitate was filtered, washed with water (100 ml) and dried under vacuum over phosphoruspentoxide. Yield, 13 g (93%), yellow powder; TLC analysis showed one product spot (Rf = 0.53; acetone:hexane=1:2, Polygram® Sil G/UV254 as adsorbent phase), MS m/z 344 (M+). The obtained product RCl2 (1 g, 2.9 mmol) was dissolved in dioxane (25 ml). Ammonia (25%, 5 ml) was added. After 15 minutes stirring at room temperature, TLC analysis showed the reaction to be completed. Over 20 minutes water (70 ml) was added. The resulting product slurry was stirred for an additional 15 minutes. The precipitate was filtered of, washed with water and dried under vacuum over phosphoruspentoxide. Yield, 0.9 g (95%), yellow powder; TLC analysis showed one product spot for RCl-NH2 (Rf = 0.5; acetone:hexane=2:3, Polygram® Sil G/UV254 as adsorbent phase), MS m/z 325 (M+). The newly synthesized dyes were tested experimentally in a 150 ml reactor, which is shown in Figure 3.13. Before the dyeing procedure started, a simple pretreatment was done to the


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cotton to improve its dyeability in supercritical carbon dioxide. In a sample flask a piece of 0.25 g of cotton was immersed in a fluid medium consists in 20 g of methanol. The pretreatment was carried out at 40°C and 1 bar by gently shaking the sample flask for 12 h. The pre-treated piece of cotton was removed from the methanol and transfer as such to the reactor for the dyeing procedure. 60% by weight of the cotton substrate of methanol remains in the pre-treated cotton. The cotton, the dye, the co-solvent and the acid were placed in the high pressure batch reactor. The amount of dye was 10 % (on weight of the fiber) and the co-solvent was used at a concentration of 2% by weight of carbon dioxide. The acids used in this study were H3PO4 in a concentration of 0.3 % (on weight fiber) and CH3COOH in a concentration of 80 % (on weight of the fiber). The reactor was sealed and 90 g of liquid carbon dioxide were introduced from the CO2 bottle via the needle valve. Subsequently, the reactor was placed in a thermostatic bath settled at 393 K. The initial pressure in the reactor was 60 bar, within 10 minutes a pressure of 300 bar was reached. After 4 hours of dyeing, the reactor was removed from the thermostatic bath and cool down under running water to reduce the pressure. When the pressure was 60 bar the reactor was completely depressurized by opening the needle valve. The reactor was opened and the piece of cotton was removed form the sample vessel. The materials were analyzed for their color strength and fixation as described in paragraph 3.4.

Figure 3.13: Supercritical CO2 cotton dyeing reactor in thermostatic bath

The first results with the difluorotriazinyl (RF2) reactive dye were tremendously good. Excellent color strength of 14 was achieved, which makes it the first commercially interesting supercritical reactive dye. The best result of supercritical dyeing of cotton until so far was a color strength of 1-2, so the improvement was significant. Figure 3.14 shows the dyed cotton from this experiment, where only the right half of the textile is extracted with acetone after dyeing. Visually, there is no difference between the color of the right and the left part, indicating a good coloration and fixation of the dye on the cotton. Under the same reaction conditions the dyeing reaction was also carried with the dichlorotriazinyl (RCl2) dye for comparison. In that case there was an unacceptable degradation of the cotton fibers. This was caused by the formation of hydrochloric acid in the dyeing reaction (Eq. 3.3). With the difluorotrazinyl dye the degradation is not observed. This can be explained by the fact that hydrogen fluoride, which is produced in the dyeing reaction with RF2, is less acidic than hydrochloric acid:


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R-OH + dye-F → RO-dye + HF (Eq. 3.7)

Figure 3.14: Piece of cotton dyed with RF2 in supercritical CO2

Next to the difluorotrazinyl (RF2) dye, also the monofluorotriazinyl dyes (RF-OCH3 and RF-NH2) were tested under the same conditions. The dyeing results are shown in Table 3.3. It can be noticed that the color strength in all cases is very good. The results for dyeing with RF-NH2 are the best without any acid added, while RF-OCH3 is doing better under acidic conditions. In all cases, the fixation is not yet optimal (>95%). Table 3.3: Supercritical cotton dyeing results (color strength and fixation) with fluorotriazinyl dyes

Dye No acid H3PO4 CH3COOH

K/S (-) Fix (%) K/S (-) Fix (%) K/S (-) Fix (%)

RCl2 decomposition decomposition decomposition RF2 14 85 - - - - RF-OCH3 10 60 21 80 14 50 RF-NH2 15 73 7 75 9 35 To compare a monofluorotriazinyl reactive dye with a monochlorotriazinyl reactive dye, the supercritical dyeing reaction with both RF-NH2 and RCl-NH2 was tested for a dyeing time of 7 hours (instead of 4 hours). The results are shown in Table 3.4. Table 3.4: Supercritical cotton dyeing results (color strength and fixation) for the monochlorotriazinyl (RCl-NH2) and the monofluorotriazinyl (RF-NH2) reactive dye in supercritical CO2

Dye No acid H3PO4 CH3COOH

K/S (-) Fix (%) K/S (-) Fix (%) K/S (-) Fix (%)

RF-NH2 15 71 10 74 17 99 RCl-NH2 5 47 4 74 4 46 The color strength with the monofluorotriazinyl reactive dye is three times better than the color strength with the monochlorotriazinyl reactive dye. When CH3COOH is used as acid in combination with RF-NH2, the fixation is as high as 99%. This result is commercially feasible, showing the possibility of a waste-free dyeing process. It can be noticed that under these conditions, even the monochlorotriazinyl dye gives promising results.


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3.6 Economic evaluation The worldwide production of cotton is around 10 million ton per year2. Conventionally, cotton is dyed in water. The main costs are the waste water consumption, purification and disposal (1 billion ton/year)2,3. Furthermore, 5 million ton/year alkali, 16 million ton/year sodium chloride, and 0.1 million ton/year dye (due to hydrolysis) are consumed in the dyeing process3. The cotton is dried, and this consumes the energy to evaporate the water adhering to the cotton (10 million/ton year, ∆Hv = 2500 kJ/kg), which is around 6.9 TWh per year. The supercritical dyeing process does not consume any water. Instead, it uses 10 m3 (5.85 ton) of CO2 per ton of cotton (at 300 bar and 393 K)3,27-30, which can be recycled but it has to be repressurized from 60 bar (ρ = 91 kg/m3 at 393 K) to 300 bar (ρ = 585 kg/m3 at 393 K) every time. The work (W) can be calculated using:

average

pdpW

ρηρη ⋅

∆≈⋅⋅= ∫

11 (Eq. 3.8)

A compressor efficiency, η, of 75% is assumed, the average density of carbon dioxide, ρaverage, is 338 kg/m3 and the pressure difference, ∆p, is 240 bar, resulting in a energy consumption of 1.5 TWh per year. Moreover, it is estimated that 0.1 million ton/year of adhering methanol (1%), and 0.03 million ton/year of acetic acid are purged3,27-30. Table 3.5 shows the prices of the resources for the conventional dyeing process in water, and the alternative supercritical dyeing process. The main differences in variable costs for the conventional process and the supercritical process are presented in Table 3.6. Table 3.5: Prices of resources in the conventional and the supercritical cotton dyeing process


Water* 2.27 €/m3 36 Alkali 105 €/ton 37 Salt 10 €/ton 38 Dye 15000 €/ton 36 Methanol 130 €/ton 39 Acetic acid 370 €/ton 40 Energy 0.05 €/kWh 36 *Price of purchasing, purification and disposal of water, data from Stork Prints B. V.

As can be seen from Table 3.6, the main costs of the conventional process are the water usage and the dye losses due to hydrolysis. In a future supercritical dyeing process, these costs can be completely prevented, resulting in a commercially attractive process without environmental pollution. At this moment, the supercritical process for dyeing of polyester is already being commercialized, showing that suitable pressurized equipment is available. It is expected that the savings per year outweigh the investment cost by far.


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Table 3.6: Main differences in variable costs of the conventional cotton dyeing process in water and the supercritical cotton dyeing process for the production of 10 million ton cotton per year

Amount

per year

Costs

(M€/year)

Water usage (ton) 1.109 2270 Alkali consumption (ton) 5.106 525 Salt consumption (ton) 16.106 160 Dye losses (ton) 0.1.106 1500 Energy consumption (kWh) 6.9.106 0.4


Total 4455

Methanol purge (ton) 0.1.106 13 Acetic acid purge (ton) 0.03.106 11 CO2 compression (kWh) 1.5.106 0.1

Supercritical process

Total 24


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3.7 Conclusions Supercritical carbon dioxide instead of water as solvent for dyeing textile can potentially eliminate the water consumption and waste production. The supercritical dyeing process is energetically more favorable as well, since the drying step of the textile is not needed. Notwithstanding all the environmental advantages of dyeing in supercritical CO2, the process will only be economical feasible if all kinds of textile can be dyed. Synthetic fibers were successfully dyed before. However, until now the dyeing of cotton was unsuccessful. This chapter shows for the first time excellent dye fixation and coloration of the cotton after being dyed with fluorotriazinyl dyes in supercritical CO2. Since cotton can now be dyed in supercritical CO2, an industrial environmentally benign textile dyeing process can be expected in the future, leading to substantial savings in water and dye consumption. Now, it is time to develop a range of dyes in order to be able to dye cotton in supercritical CO2 in all colors, and start scaling up the process.


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3.8 References

1. Chemical structure of cotton: http://en.wikipedia.org/wiki/Cellulose

2. Johnson, T.; World Fiber Demand 1890-2050 by Main Fiber Type, Chem. Fibers Int. 1999, 49 (6), 455–459.

3. Fernandez Cid, M. V.; Van Spronsen, J.; Van Der Kraan, M.; Veugelers, W. J. T.;

Woerlee, G. F.; Witkamp, G. J.; Excellent Dye Fixation on Cotton Dyed in Super-critical Carbon Dioxide Using Fluorotriazine Reactive Dyes, Green Chem. 2005, 7

(8), 609-616.

4. Blackburn, R. S.; Burkinshaw, S. M.; A Greener Approach to Cotton Dyeings with Excellent Wash Fastness, Green Chem. 2002, 4 (1), 47–52.

5. Cai, Y.; Pailthorpe, M. T.; David, S. K.; A New Method for Improving the Dyeability

of Cotton with Reactive Dyes, Textile Res. J. 1999, 69 (6), 440–446.

6. Burkinshaw, S. M.; Mignanelli, M.; Froehling, P. E.; Bide, M. J.; The Use of Dendrimers to Modify the Dyeing Behavior of Reactive Dyes on Cotton, Dyes

Pigments 2000, 47 (3), 259–267.

7. Blackburn, R. S.; Burkinshaw, S. M.; Treatment of Cellulose with Cationic, Nucleophilic Polymers to Enable Reactive Dyeing at Neutral pH without Electrolyte Addition, J. Appl. Polymer Sci. 2003, 89 (4), 1026–1031.

8. Knittel D.; Schollmeyer, E.; Environmentally Friendly Dyeing of Synthetic Fibres and

Textile Accessories, Int. J. Clothing Sci. Technol. 1995, 7 (1), 36–45.

9. Montero, G. A.; Smith, C. B.; Hendrix, W. A.; Butcher, D. L.; Supercritical Fluid Technology in Textile Processing: An Overview, Ind. Eng. Chem. Res. 2000, 39 (12), 4806–4812.

10. Bach, E.; Cleve, E.; Schollmeyer, E.; Past, Present and Future of the Supercritical

Fluid Dyeing Technology - An Overview, Rev. Prog. Color. 2002, 32, 88–102.

11. Marr, R.; Gamse, T.; Use of Supercritical Fluids for Different Processes Including New Developments - A Review, Chem. Eng. Proc. 2000, 39 (1), 19–28.

12. Beckman, E. J.; Supercritical and Near-Critical CO2 in Green Chemical Synthesis and

Processing, J. Supercrit. Fluids 2004, 28 (2-3), 121–191.

13. Johnston, K. P.; Supercritical Fluids, In: Grayson, M.; Eckroth, D., Eds. Kirk-Othmer

Encyclopedia of Chemical Technology, 3rd ed., John Willey & Sons: New York, USA, 1984.

14. Saus, W.; Knittel, D.; Schollmeyer, E.; Dyeing of Textiles in Supercritical Carbon

Dioxide, Textile Res. J. 1993, 63 (3), 135–142.


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15. Bach, E.; Cleve, E.; Schollmeyer, E.; Dyeing of Poly(Ethylene Terephthalate) Fibers in Supercritical Carbon Dioxide, Proc. 3rd

Int. Symp. High Pressure Chem. Eng., Zurich, Switzerland, 1996, pp. 581–586.

16. Bach, E.; Cleve, E.; Schollmeyer, E.; Bork, M.; Körner, P.; Experience With the Uhde

CO2-Dyeing Plant on Technical Scale, Part 2: Concepts for the Development of the Pilot Plant in Respect of a Scaling Up of the Machine, Melliand Int. 1998, 4, 192–194.

17. Schmidt, A.; Bach, E.; Schollmeyer, E.; The Dyeing of Natural Fibers with Reactive

Disperse Dyes in Supercritical Carbon Dioxide, Dyes Pigments 2003, 56 (1), 27–35.

18. Schmidt, A.; Bach, E.; Schollmeyer, E.; Supercritical Fluid Dyeing of Cotton Modified with 2,4,6-Trichloro-1,3,5-triazine, Coloration Technol. 2003, 119 (1), 31–36.

19. Maeda, S.; Hongyou, S.; Kunitou, K.; Mishima, K.; Dyeing Cellulose Fibers with

Reactive Disperse Dyes in Supercritical Carbon Dioxide, Textile Res. J. 2002, 72 (3), 240–244.

20. Gebert, B.; Saus, W.; Knittel, D.; Buschmann, H. J.; Schollmeyer, E.; Dyeing Natural

Fibers with Disperse Dyes in Supercritical Carbon Dioxide, Textile Res. J. 1994, 64

(7), 371–374.

21. Özcan, A. S.; Clifford, A. A.; Bartle, K. D.; Broadbent, P. J.; Lewis, D. M.; Dyeing of Modified Cotton Fibres with Disperse Dyes from Supercritical Carbon Dioxide, J.

Soc. Dyers Colourists 1998, 114 (5), 169–173.

22. Beltrame, P. L.; Castelli, A.; Selli, E.; Mossa, A.; Testa, G.; Bonfatti, A. M.; Seves, A.; Dyeing of Cotton in Supercritical Carbon Dioxide, Dyes Pigments 1998, 39 (4), 335–340.

23. Sawada, K.; Takagi, T.; Jun, J. H.; Ueda, M.; Lewis, D. M.; Dyeing Natural Fibres in

Supercritical Carbon Dioxide Using a Nonionic Surfactant Reverse Micellar System, Coloration Technol. 2002, 118 (5), 233–237.

24. Schmidt, A.; Bach, E.; Schollmeyer, E.; Damage to Natural and Synthetic Fibers

Treated in Supercritical Carbon Dioxide at 300 Bar and Temperatures Up to 160°C, Textile Res. J. 2002, 72 (11), 1023-1032.

25. Fernandez Cid, M. V.; Van Der Kraan, M.; Veugelers, W. J. T.; Woerlee, G. F.;

Witkamp, G. J.; Kinetics Study of a Dichlorotriazine Reactive Dye in Supercritical Carbon Dioxide, J. Supercrit. Fluids 2004, 32 (1-3), 147–152.

26. Bentley, T. W.; Ratcliff, J.; Renfrew, A. H. M.; Taylor, J. A.; Homogeneous Models

for the Chemical Selectivity of Reactive Dyes on Cotton – Development of Procedures and Choice of Model, J. Soc. Dyers Colourists 1995, 11 (6), 288–293.

27. Fernandez Cid, M. V.; Gerstner, K. N.; Van Spronsen, J.; Van Der Kraan, M.;

Veugelers, W. J. T.; Woerlee, G. F.; Witkamp, G. J.; Novel Process to Enhance the


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Dyeability of Cotton in Supercritical Carbon Dioxide, Textile Res. J. 2007, 77 (1), 38-46.

28. Fernandez Cid, M. V.; Van Spronsen, J.; Veugelers, W. J. T.; Woerlee, G. F.; Dyeing

of Fibrous Substrate with Reactive Dyestuff in Supercritical or Near Supercritical Carbon Dioxide, International Patent WO 2006/049504 A2 (2006).


Woerlee, G. F.; Witkamp, G. J.; A Significant Approach to Dye Cotton in Supercritical Carbon Dioxide with Fluorotriazine Reactive Dyes, J. Supercrit. Fluids 2007, 40 (3), 477-484.


Woerlee, G. F.; Witkamp, G. J.; Acid-Catalyzed Methanolysis Reaction of Non-Polar Triazinyl Reactive Dyes in Supercritical Carbon Dioxide, J. Supercrit. Fluids 2007, 39

(3), 389-38.

31. March, J.; Advances in Organic Chemistry: Reactions, Mechanisms and Structure, Wiley-Interscience: New York, USA, 1992.

32. Hunter, A.; Renfrew, M.; Rettura, D.; Taylor, J. A.; Whitmore, J. M. J.; Williams, A.;

Stepwise versus Concerted Mechanisms at Trigonal Carbon: Transfer of the 1,3,5-Triazinyl Group between Aryl Oxide Ions in Aqueous Solution, J. Am. Chem. Soc. 1995, 117 (20), 5484–5491.

33. Horrobin, S.; The Hydrolysis of Some Chloro-1,3,5-triazines: Mechanism, Structure

and Reactivity, J. Chem. Soc. 1963, 4130–4145.

34. Johnson, A.; The Theory of Coloration of Textiles, 2nd ed., Society of Dyers and Colourists: Bradford, UK, 1995.

35. Trotman, E. R.; Dyeing and Chemical Technology of Textile Fibres, 6th ed., Charles

Griffin & Company Ltd.: High Wycombe, UK, 1984.

36. Van der Kraan, M.; Process and Equipment Development for Textile Dyeing in

Supercritical Carbon Dioxide, Dissertation Delft University of Technology: Delft, Netherlands, 2005.

37. Soda market prices 2008: http://www.the-innovation-group.com/ChemProfiles/Soda%

20Ash.htm

38. Sodium chloride market prices 2006: http://www.ecplaza.net/tradeleads/seller/38566 92/salt_for_food_purposes.html

39. Methanol market price 2006: http://www.icis.com/v2/chemicals/9076034/methanol/

pricing.html

40. Acetic acid market price 2009: http://www.chemicalexplorer.com/category/keywords/ acetic-acid

4 Oxidation of linoleic acid in supercritical

carbon dioxide By: J. van Spronsen, M. C. Kroon, K. Mulia, G. J. Witkamp, I. W. C. E. Arends and F. Hollmann

___________________________________________________________________________

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4. Oxidation of linoleic acid in supercritical carbon dioxide

4.1 Introduction In this chapter supercritical carbon dioxide (CO2) is used as a solvent for the oxidation of linoleic acid. Linoleic acid is an essential unsaturated omega-6 fatty acid that is found in the lipids of cell membranes, and also abundantly available in vegetable oils. Omega-6 deficiency symptoms include dry hair, hair loss and poor wound healing1,2. The structure of linoleic acid is shown in Figure 4.1.

Figure 4.1: Structure of linoleic acid

Linoleic acid can be converted to its two corresponding hydroperoxides by means of oxidation. These two hydroperoxide isomers, 9-(S)-hydroperoxydeca-10,12-dienoic acid (9-HPOD) and 13-(S)-hydroperoxydeca-9,11-dienoic acid (13-HPOD), have a high value as pharmaceuticals. They are used as treatment against cancer, cystic fibrosis, dermatitis and diabetes3,4. The structures of 9-HPOD and 13-HPOD are shown in Figure 4.2. Figure 4.2: Structures of 9-HPOD (left) and 13-HPOD (right)

The oxidation of linoleic acid to the hydroperoxide isomers is conventionally carried out in water as solvent5,6. The reaction can be carried out either enzyme-catalyzed5 or without catalyst6. When the reaction is carried out without catalyst, both 9-HPOD and 13-HPOD are obtained as products6. However, when the reaction is catalyzed by the enzyme lipoxygenase (from soybean), a selectivity towards the 13-HPOD isomer exists. The problem with water as solvent is the low solubility of fatty acids and oxygen, so that the reaction rate is mass-transfer limited. Instead, the oxidation of linoleic acid can also be carried out in supercritical CO2 as solvent7. Advantages of using supercritical CO2 over aqueous media as solvents include (i) high solubility of hydrophobic reactants and gases (such as oxygen) in supercritical CO2 resulting in high reaction rates, (ii) no microbial contamination since microorganisms do not grow in non-aqueous environments, and (iii) the enzyme’s insolubility in supercritical CO2 will ensure easy separation from the products. Perhaps the most important advantage of supercritical CO2

4. Oxidation of linoleic acid in supercritical carbon dioxide ___________________________________________________________________________

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as solvent for reactions is that the solubility of a material in CO2 can be controlled by adjusting the system pressure and by addition of small amounts of co-solvents such as methanol and acetone. Chikere et al.7 carried out the lipoxygenase-catalyzed oxidation of linoleic acid in both aqueous media and supercritical CO2. The differences in conditions and reaction rate are shown in Table 4.1. Moreover, the conversion as function of time in both cases is shown in Figure 4.3. Table 4.1: Comparison of conditions and space-time yield for the lipoxygenase-catalyzed oxidation of linoleic acid in water and supercritical CO2

Aqueous media Supercritical CO2

Temperature (oC) 0 33 Pressure (bar) 1 250 Initial reactant concentration (mM) 6 100 Space-time yield (M/s/mg) 5x10-5 6x10-3

Figure 4.3: Production of 13-HPOD (mM) by the lipoxygenase-catalyzed oxidation of linoleic acid in water (left) and in supercritical CO2 (right)

It can be observed that the reaction rate in supercritical CO2 is much higher than the reaction rate in water. However, the decomposition of the product hydroperoxide is also much faster in supercritical CO2 because of the higher reaction temperature. In this chapter, the work by Chikere et al.7 in supercritical CO2 is scaled up in order to produce large amounts of 13-HDOP. The lipoxygenase-catalyzed reaction will take place in a newly built supercritical CO2 reactor.


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4.2 Experimental 4.2.1 Materials Linoleic acid (technical grade from Sigma-Aldrich) was used for the reaction. Soybean lipoxidase (Sigma-Aldrich), the enzyme, was immobilized on Eupergit C250L, as described previously7. Diethyl ether (anhydrous) was used for extraction, and methanol (technical grade) for washing, both from J. T. Baker, were also used. 4.2.2 Experimental set-up The supercritical batch reactor set-up is shown in Figure 4.4. The reactor vessel has a total volume of 500 ml. It is fitted with a stirrer that can withstand a maximum pressure of 150 bar. The reactor contains two cavities at the bottom as inlet and outlet. The reaction vessel has a micro-welded metal mesh at the bottom of the cup. The gaseous CO2 is liquefied by cooling, and is pumped using a CO2 pump through the heat exchanger, where it is heated above its critical temperature. The supercritical CO2 is then let into the reaction vessel at high pressure. There are valves at the bottom of the reactor, to allow the inflow of the gases (CO2 and air) and to allow the outflow of the product along with the supercritical CO2. The pressure of the outflow is reduced to recover the product from the CO2.

Figure 4.4: Process flow diagram for the lipoxygenase-catalyzed oxidation of linoleic acid in supercritical CO2 and subsequent separation (batch-wise)


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4.2.3 Experimental procedure First, the reaction kinetics for the batch-wise production of 13-HPOD in supercritical CO2 were measured. At the beginning of the experiment, all the valves were closed tightly. Thereafter, 1 ml of linoleic acid was added via the inlet. The reaction vessel (cup) was placed in the reactor and 1 ml wet suspension of immobilized lipoxidase enzyme was added along the corners of the cup, in order to avoid the flow of wet enzyme on to the metal mesh at the bottom. The stirrer was fitted and the reactor was closed tightly. Pressurized air was let in until an air pressure of 2.7 bar was reached. This was followed by the inlet of supercritical CO2, until the pressure of the gas reached 150 bar. At this point, the CO2 pump was shut down and the stirrer was switched on. This was the start of the reaction. The parameters for the reaction conditions are tabulated in Table 4.2. Table 4.2: Parameters for the lipoxygenase-catalyzed oxidation of linoleic acid in supercritical CO2

Parameter Value

Reactor volume 500 ml Reaction temperature 35° C Total pressure 150 bar Amount of air 1.47 g ( 2.7 bar air) Amount of linoleic acid 1 ml Amount of CO2 200 g (150 bar) Amount of immobilized enzyme 1 ml of wet suspension

After the end of the reaction, the supercritical CO2 was decompressed. The resulting cooling of the outlet valves and tubes was circumvented by heating them using a heating gun. The reactor was flushed with diethyl ether solvent and all the products dissolved in the solvent were collected from the outlet and immediately stored at -20° C. The product was then extracted by removing the solvent by evaporation (in a rotavap) at 35-45° C. To check the kinetics of the reaction, the reaction products were analyzed at different reaction times (15, 30, 45, 60 and 90 minutes). The analysis of the reaction products were done by Reversed Phase High Performance Liquid Chromatography (RP-HPLC). The X-terra RP18 column (3.5µm * 4.6 * 150 mm) was used. A Waters 515 HPLC system was used with a SHIMADZU SPD-10A VP UV-VIS detector. The mobile phase was methanol:water (70:30) with 0.1% acetic acid. The UV-VIS measurement was done at 235 nm. The running time was 22 min. The samples were prepared by diluting the product 100 times in pure methanol. A comparison of the reaction carried out in the supercritical CO2 reactor using different forms of enzyme was carried out. All the conditions were the same as given above. The only difference being the form of enzyme added in the cavity for reaction. The comparison was done with three different enzyme forms and a blank experiment:

1) 5 mg of lyophilized powder of enzyme ( commercially available from Sigma-Aldrich) 2) 5 mg/ml enzyme solution in borate buffer (pH 9), 50mM 3) Enzyme immobilized on commercially available Eupergit C 250L having a rough

protein content of 5 mg 4) A control reaction with no enzyme, keeping all the other conditions constant


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4.3 Results and discussion The kinetics of the reaction was determined by analyzing the reactant and product concentrations at different time intervals. RP-HPLC analysis showed 3 peaks: (i) linoleic acid substrate, (ii) 13-HPOD isomer, and (iii) 9-HPOD isomer. A typical HPLC chromatogram is shown in Figure 4.5.

Figure 4.5: Typical chromatogram showing three major peaks: (i) linoleic acid peak (left), (ii) 13-HPOD peak (middle), and (iii) 9-HPOD peak (right)

Figure 4.6 presents the progress of the reactant and product peaks over time. In this way a plot of the reaction kinetics is obtained.

time (min)

0 20 40 60 80 100

Pe

ak

Are

a (

a.u

.)

0

1e+6

2e+6

3e+6

4e+6

9-HPODE

13-HPODE

Linoleic acid

Figure 4.5: Kinetics of the lipoxygenase-catalyzed conversion of linoleic acid into 13-HPOD and 9-HPOD in supercritical CO2


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From Figure 4.5 it can be seen that the reaction rate is high, and that an overall conversion of 58.7% of the linoleic acid can be reached. It can also be noticed that the selectivity to the 13-HPOD isomer is not high. Both the 13-HPOD and the 9-HPOD isomers are produced. This is contrary to literature7, which states that the only product from the lipoxygenase-catalyzed oxidation of linoleic acid is the 13-HPOD isomer. An explanation for the observation of both products is that the reaction is non-catalytic, and not enzyme-catalyzed. In that case, both isomers are produced6. This will be tested next. Finally, it can be noticed that considerable decomposition of the products takes place after 30 minutes, probably as a result of the high temperature and pressure (compared to the reaction in water)8. This should be prevented as much as possible. Because the selectivity of the enzyme was poor in supercritical CO2, it was hypothized that the reaction is non-catalytic instead. To verify any enzymatic activity, a control reaction was done for 15 minutes in the absence of any enzyme, but in the presence of air. The results are graphically demonstrated in Figure 4.6.

time (min)

0 20 40 60 80 100

Pe

ak

Are

a (

a.u

.)

0

1e+6

2e+6

3e+6

4e+6 9-HPODE

13-HPODE

Linoleic acid

Blank 9-HPODE

Blank 13-HPODE

Figure 4.6: Comparison between the lipoxygenase-catalyzed oxidation and the non-catalytic oxidation (blank experiment) of linoleic acid in supercritical CO2

The comparison shows that the oxidation of the sample without catalyst is significant. The difference between the results with and without enzyme added falls within the analysis uncertainty. The production of both isomers in a ratio close to 50:50 also indicates that the reaction is non-catalytic and not enzymatic. One could state that the enzyme does not have any function at all in this reaction. In literature7, on the contrary, it was stated that only 13-HPOD was produced. A closer look at this previous article7 shows that the concentration of both isomers was measured together (one peak), so that they could not differentiate between the two isomers. It was simply assumed that only the 13-HPOD isomer was produced because of the addition of the enzyme. Here, it is concluded that this assumption was wrong and that they probably also carried out the non-catalytic oxidation instead.


- 73 -

The hypothesis that the oxidation is not catalyzed instead of enzyme-catalyzed was further checked by testing different enzyme forms for 15 minutes:

1) 5 mg of lyophilized powder of enzyme ( commercially available from Sigma-Aldrich) 2) 5 mg/ml enzyme solution in borate buffer (pH 9), 50mM 3) Enzyme immobilized on commercially available Eupergit C 250L having a rough

protein content of 5 mg 4) A control reaction with no enzyme, keeping all the other conditions constant

The results are presented in Figure 4.7.

Linoleic acid 13-HPOD 9-HPOD

Pe

ak

are

a (

a.u

)

0

4e+5

8e+5

1e+6

2e+6

2e+6

Blank

5 mg powdered enzyme

5 mg enzyme in buffer solution

25 mg immobilized enzyme

Figure 4.7: Comparison of the peak areas of reactant and products from the linoleic acid oxidation by using different enzyme forms

Figure 4.7 shows that all enzyme forms do not significantly increase the oxidation rate compared to the blank experiment. Moreover, in all cases a mixture of the 9-HPOD and the 13-HPOD isomers is obtained, indicating that oxidation reaction is always occurring. If the reaction would have been enzyme-catalyzed, then a larger difference between the different enzyme forms was expected. Again, it is concluded that the enzyme does not have any function at all in the reaction. Finally, the oxidation of linoleic acid in supercritical CO2 is compared to the same reaction in water with the enzyme immobilized on Eupergit C 250L. Figure 4.8 shows this comparison graphically. First of all, it can be noticed that the reaction rate in supercritical CO2 is much higher compared to the reaction rate in water. This was expected due to the lack of mass transfer limitation in the supercritical CO2 reactor. Moreover, it can be observed that the


- 74 -

oxidation in water is more likely to be enzyme-catalyzed, because the ratio of 13-HPOD over 9-HPOD is increasing over time. The reaction was thus selective to the formation of 13-HPOD compared to 9-HPOD, indicating that the enzyme is functioning. On the contrary, both products were produced at almost equal rate in the supercritical CO2 reactions. Thus, it can be concluded that the reaction in water is enzyme-catalyzed, whereas the reaction in supercritical CO2 is non-catalytic.

time (min)

0 20 40 60 80 100

Pe

ak

Are

a (

a.u

.)

0.0

5.0e+5

1.0e+6

1.5e+6

2.0e+6

2.5e+6

3.0e+6

3.5e+6

9-HPOD (CO2/LOX)

13-HPOD (CO2/LOX)

13-HPOD (aq)

9-HPOD (aq)

9-HPOD (CO2)

13 HPOD (CO2)

Figure 4.8: Comparison of the oxidation of linoleic acid in water (with addition of lipoxygenase) and supercritical CO2 (with/without addition of lipoxygenase)


- 75 -

4.4 Economic evaluation The products of the oxidation of linoleic acid have a high value as pharmaceuticals and/or skin care products. Because the production volumes are not large, the economical benefits of replacing water by supercritical CO2 will be relatively small. However, the oxidation of linoleic acid in supercritical CO2 is a nice example of process intensification. It is interesting to carry out many other oxidations in supercritical CO2 because of the high solubility of both oxygen and non-polar substrates. Oxidations are conventionally carried out in water, and suffer from the disadvantage of the low oxygen solubility in water. Volatile organic solvents are not suitable for oxidations, because of the safety risks concerning flammability and explosiveness. When supercritical CO2 is used as solvent for oxidations instead, the higher oxygen solubility results in higher reaction rates. Finally, supercritical CO2 allows reactions to be carried out continuously and with easy product separation.


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4.5 Conclusions The oxidation of linoleic acid to its corresponding hydroperoxides 13-HPOD and 9-HPOD can take place at higher rates in supercritical CO2 as alternative solvent compared to water. Reason is that the reactants (linoleic acid and oxygen) show higher solubility in supercritical CO2 than in water. Therefore, the reaction is no longer mass transfer limited. Another difference is that the oxidation reaction in supercritical CO2 is not catalyzed, whereas the reaction in water is enzyme-catalyzed. This was found by analysis of the products. In supercritical CO2 both the 13-HPOD and the 9-HPOD isomers were produced, whereas a selectivity towards to 13-HPOD isomer was found in water as solvent. Because the reaction in supercritical CO2 is non-catalytic, the enzyme does not have any function and/or influence. The form of the enzyme is thus irrelevant. Although the supercritical CO2 does not seem to be a good solvent for the enzyme, it is still a promising solvent for chemical oxidation. Supercritical CO2 allows reactions to be carried out continuously, without any mass transfer limitations, and with easy product separation. Therefore, it is a good solvent to scale up the oxidation process.


- 77 -

4.6 References

1. Cunnane, S.; Anderson, M.; Pure Linoleate Deficiency in the Rat: Influence on Growth, Accumulation of n-6 Polyunsaturates, and (1-14C) Linoleate Oxidation, J.

Lipid Res. 1997, 38 (4), 805-812.

2. Ruthig, D. J.; Meckling-Gill, K. A.; Both (n-3) and (n-6) Fatty Acids Stimulate Wound Healing in the Rat Intestinal Epithelial Cell Line, IEC-6, J. Nutrit. 1999, 129

(10), 1791–1798.

3. Egmond, A. W. van; Kosorok, M. R.; Koscik, R.; Laxova, A.; Farrell, P. M.; Effect of Linoleic Acid Intake on Growth of Infants with Cystic Fibrosis, Am. J. Clin. Nutrit. 1996, 63 (5), 746-752.

4. Horrobin, D. F.; Fatty Acid Metabolism in Health and Disease: The Role of ∆-6-

Desaturase, Am. J. Clin. Nutrit. 1993, 57, 732S-736S.

5. Gardner, H. W.; Weisleder, D.; Hydroperoxides from Oxidation of Linoleic and Linolenic Acids by Soybean Lipoxygenase: Proof of the Trans-11 Double Bond, Lipids 1972, 7 (3), 191-193.

6. Chan, H. W. S.; Levett, G.; Autoxidation of Methyl Linoleate: Separation and

Analysis of Isomeric Mixtures of Methyl Linoleate Hydroperoxides and Methyl Hydroxylinoleates, Lipids 1977, 12 (1), 99-104.

7. Chikere, A. C.; Galunsky, B.; Overmeyer, A.; Brunner, G.; Kasche, V.; Activity and

Stability of Immobilised Soybean Lipoxygenase-1 in Aqueous and Supercritical Carbon Dioxide Media, Biotechnol. Lett. 2000, 22 (22), 1815-1821.

8. Tedjo, W.; Eshtiaghi, M. N.; Knorr, D.; Impact of Supercritical Carbon Dioxide and

High Pressure on Lipoxygenase and Peroxidase Activity, J. Food Sci. 2006, 65 (8), 1284-1287.

5 Foaming of polystyrene using supercritical

carbon dioxide By: J. van Spronsen, J. P. H. van Luijtelaer, A. Stoop, J. C. Scheper, T. J. de Vries, G. J. Witkamp and M. C.

Kroon

___________________________________________________________________________

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5. Foaming of polystyrene using supercritical carbon dioxide

5.1 Introduction Polystyrene (PS) foams are widely used as packaging materials and as heat insolators. They have a low density, a low thermal conductivity, and a relatively high impact strength1. According to branche-organization Stybenex2, the market for PS foam in the Netherlands is 60,000 ton per year. The density of this PS foam is around 20 kg.m-3, resulting in a production of 3,000,000 m3 per year. The average price of PS foam is € 65,- per cubic meter. Thus, the PS foam turnover in the Netherlands is around 200 M€ per year. Conventionally, PS foam is produced using pentane (6-8 wt%) as foaming/blowing agent, because of its sufficient solubility in PS and its relative high volatility1. However, the explosiveness and the volatile nature of pentane, resulting into emissions into the atmosphere, are disadvantageous. There are two conventional process options for the production of PS foam:

- Expandable polystyrene (EPS) process option - Extruded polystyrene (XPS) process option

In the EPS process option, pentane saturated PS beads are produced. The beads are cured (foamed) and sintered in a mould. Figure 5.1 shows the overall EPS process, including the (partly) burning of the released pentane and the storage of the PS foam.

Figure 5.1: Conventional production of PS using the EPS process option

In the XPS process option, a molten mixture of PS and pentane is produced in an extruder, which is pressed through a so-called ‘die-plate’ at the end of the extruder. The die-plate is used to shape the foam. Thereafter, the liquid foam is cooled in order to solidify. When the foam dimensions are too large, the cooling process is too slow, resulting in significant

EPS beads production

transport EPS curing & sintering

Storage Use Polystyrene

Pentane

Pentane Pentane

Pentane

Energy

After burner

Natural gas

Pentane, CO2

5. Foaming of polystyrene using supercritical carbon dioxide ___________________________________________________________________________

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collapse of the foam. Figure 5.2 shows the conventional production process of PS foam using the XPS process option, including the (partly) burning of the released pentane and the storage of the PS foam.

Figure 5.2: Conventional production of PS using the XPS process option

The difference between both forms of PS foam is the higher impact strength of XPS due to a higher density versus the higher thermal isolation value per unit mass of EPS due to the lower density. In principle, all pentane has to be removed from the final PS foam product. Therefore, the PS foam cannot be used directly, but has to be stored for at least 4 weeks before a sufficient amount of pentane has been evaporated. A small part of the blowing agent remains in the product (<1%). The pentane that escapes during PS production is as much as possible collected and burned in a afterburner. A large excess of air is necessary in order to remain outside the explosion limits. In reality, only about 40% of the pentane is eventually burned, the rest of the pentane eventually ends up in the environment1. In this work, the foaming process will be carried out with supercritical carbon dioxide (CO2) as environmentally benign blowing agent instead of pentane. Therefore, any problems with pentane explosiveness and emissions will be prevented. Another difference is that the foam can be solidified faster because CO2 expands rapidly without any collapse of the foam. Therefore, it is expected that larger blocks of PS foam with lower density can be produced3,4.

XPS foaming

Storage Use Polystyrene

Pentane

Pentane Pentane

Energy

After burner

Natural gas

Pentane, CO2


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5.2 Supercritical foaming of polystyrene When PS is foamed with supercritical CO2 as blowing agent, the only by-product is CO2, which is an inert gas that is naturally occurring in the atmosphere. No pentane is produced, and no afterburner is needed. Energy is only necessary for pressurizing the CO2 and extrusion of the PS foam. After production, the foam can be directly used. It is not necessary to store the foam for at least 4 weeks in order to remove all blowing agent, because CO2 directly evaporates after pressure release3,4. Figure 5.3 shows the production process of PS foam with supercritical CO2 as blowing agent.

Figure 5.3: Alternative foaming of PS with supercritical CO2 as blowing agent

Many studies to the foaming of PS with supercritical CO2 have been carried out previously5-

21. Some involve the determination of the fundamental properties of PS + CO2 mixtures, such as the CO2 solubility in PS5,6, the diffusivity of CO2 in PS5, the influence of CO2 on the glass transition temperature of PS7,8, the influence of CO2 on the viscosity of PS8,9, and the interfacial tension between PS and CO2

10,11. Other studies try to correlate these fundamental properties to the characteristics of the foaming process12,13. A basic foaming process can be divided into four steps4: (i) formation of a homogeneous solution composed of the foaming agent (CO2) and the polymer melt (PS), (ii) cell nucleation induced by a pressure decrease or a temperature increase, (iii) cell growth and coalescence to the desired volume, and (iv) stabilization and retention of the expanded form. The final foam structure and density is determined by the conditions under which all steps are performed, either batchwise or continuously. Generally, the continuous extrusion process is more attractive because of the higher productivity and the easier process control. The mechanism of cell nucleation and growth is most commonly investigated12-19. In most foaming applications a pressure drop is used in order to create supersaturation4. When clusters of CO2 gas molecules are greater than the critical size, the activation energy is overcome and nucleation occurs. The greater the supersaturation, the smaller the activation energy. The major parameters in the extrusion process are therefore the CO2 solubility, the pressure drop and the temperature12,13. Additives such as clay nanoparticles, carbon nanofibers or minerals can be used to adjust the nucleation rate, presumably enhancing the rate by significantly decreasing the activation barrier14-16. Shear-induced nucleation was also studied17,18, as well as the effect of the polydispersity of the PS on the foam structure19.

Supercritical foaming Use

Polystyrene

CO2

CO2

Energy


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The effect of the extruder configuration itself on the foam properties has received much less attention. The effect of different screw types on the viscosity of the PS + CO2 system was investigated by Lee et al.9 Xu et al.20,21 studied the influence of the die geometry on the cell nucleation of PS foams blown with CO2. However, in that work only single hole dies were investigated, and no foam densities were reported. Foam density is an important parameter, because it largely determines the cost price of the material. Here, we investigate the effect of multiple hole dies on the structure and density of extruded PS foams with CO2 as blowing agent. The concept of multiple hole die extrusion has never been reported for PS foaming with CO2. It is expected that larger blocks of PS foam can be produced using multiple hole dies compared to single hole dies, because the different strings can melt together. This may have an influence on the foam structure, overall foam density and production rate, as compared to single hole die extrusion. We started measuring foam properties of single hole die extrusion. Based on the radial expansion in the single hole die experiments, we chose the hole diameter and hole distances in the multiple hole die, which we used in later experiments.


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5.3 Experimental 5.3.1 Materials PS beads, STYRON 660®, were supplied by Dow. The CO2 used for the experiments was supplied by HoekLoos B.V. and had a purity of 99.995 mol%. 5.3.2 Extrusion system A schematic of the extrusion system used for the experiments is shown in Figure 5.4. At the core of the system is a Werner & Pfleiderer co-rotating twin screw extruder, type ZSK25 P8.2E, with a screw diameter of 25 mm.

Figure 5.4: Schematic of the extrusion system: (1) variable-speed motor, (2) gear box, (3) hopper, (4) co-rotating twin screw extruder, (5) CO2 pump, (6) temperature sensors, (7) pressure transducer, (8) die, and (9) data acquisition and control system.

The screw configuration is shown in more detail in Figure 5.5. The screws are operated by a 6 kW AEG motor, type GK13.04, with a gear box added in order to control the rotation speed. The screws are contained in a 1.20m length barrel, consisting of 11 elements or zones that can be cooled or heated separately. The temperature of each element is controlled by a separate temperature controller. Temperature in each element is also measured with PT-100 temperature sensors with an accuracy of ± 0.01 oC. A pressure transducer, type Dynisco MDA 462, measures the pressure at the die with an accuracy of ± 0.5 bar.

3

1 2

4

5

6

7

8

9


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Figure 5.5: Schematic of the screw configuration with its 11 elements, where the PS is inserted in the 1

st element and the CO2 is added between the 5

th and 6

th element. Other optional points of insertion

are located between the 6th

and 7th element, between the 8

th and 9

th element, and in the 11

th element.

The polymer is added to the 1st element of the barrel with a Hethon feeder as hopper. CO2 is pumped into the barrel between the 5th and 6th element with an Orlita pump, type MH2S 18/66. The CO2 flow rate is measured with a Siemens Sitrans FC Mass 6000 mass flow meter. The foams exits the extruder via the die. Data acquisition is performed with a Labview® system. A picture of the total equipment is shown in Figure 5.6.

Figure 5.6: Extrusion system used in the experiments

5.3.3 Dies Three single hole dies were constructed and tested with a diameter of 2.0, 1.0 and 0.50 mm and a length of 8.0, 8.0 and 4.0 mm, respectively. A multiple hole die with seven holes was also constructed on basis of the experimental results with the single hole dies. Each of these seven holes had a diameter of 0.90 mm and a path length of 4.0 mm. The holes were arranged in two rows in a trigonal arrangement with 2.5 mm of space between each hole (see Figure 5.7).


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Figure 5.7: Schematic of the multiple hole die consisting of seven 0.90 mm holes in a trigonal arrangement with 2.5 mm of space between each hole.

5.3.4 Experimental procedure

At the start of each experiment all elements of the extruder barrel were heated to 180 oC. Next, the screw of the extruder was started at the required rotational speed and the addition of polymer was started at a constant flow rate. At the moment that the pressure in the die increased to 70 bar the addition of CO2 was started at the chosen flow rate. The temperature of the elements was lowered stepwise maintaining a maximum temperature difference between each zone of about 10 oC, with the lowest temperature set point at the die end of the extruder. Samples of the foam were collected when stable operation (producing dimensionally stable foam without any collapse) was reached. The size and shape of the polymer cells was determined by Scanning Electron Microscopy (SEM) from Jeol, type JSM-5400. The density of the foam was determined by measuring the water volume displacement after submerging a weighted piece of PS foam.

0.9 mm

2.5 mm


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5.4 Results and discussion The first step in the development of a multiple hole die is the determination of the effect of the single hole size on the PS foam properties. Three single hole dies were constructed and tested. These dies had a diameter of 2.0 mm, 1.0 mm and 0.50 mm, and a length of 8.0 mm, 8.0 mm and 4.0 mm, respectively. The foaming conditions were optimized to produce a foam that was dimensionally stable after extrusion with the lowest possible density. The optimized conditions of the experiments with the three single hole dies are shown in Table 5.1. The results with regard to the production rate, overall foam density and foam structure are presented in Table 5.2. Table 5.1. Optimized conditions (temperatures in the different elements, T1 to T11; pressure at the die,

p; PS addition rate, φPS; CO2 addition rate, φCO2; screw torque, τ ; screw speed, ω) for PS foaming experiments with supercritical CO2 as blowing agent for three different single hole dies and the multiple hole die.

Conditions 2.0 mm die 1.0 mm die 0.50 mm die multi hole die

T1 (°C) 145 150 150 150 T2 (°C) 160 160 170 165 T3 (°C) 170 175 180 180 T4 (°C) 175 180 180 180 T5 (°C) 165 165 165 165 T6 (°C) 150 150 150 150 T7 (°C) 125 130 135 135 T8 (°C) 125 125 125 125 T9 (°C) 130 115 115 115 T10 (°C) 130 110 110 100 T11 (°C) 125 110 120 110 p (bar) 100 160 180 150 φPS (kg.h-1) 9.0 3.6 0.40 7.0 φCO2 (kg.h-1) 0.40 0.17 0.08 0.35 τ (N.m) 7.0 5.2 5.6 7.0 ω (rpm) 100 100 130 100

For the 2.0 mm die, the extruder operated at a pressure of about 100 bar and a torque of 7.0 Nm. The production rate was 9.0 kg of PS foam per hour. The PS string produced had a diameter of 12 mm and a density of 30 kg/m3. Figure 5.8 shows the PS foam produced, and the SEM pictures (Figure 5.9) show that the cells with a size of about 70 µm have an open structure. Table 5.2. Density, ρ, production rate, φPS, and foam string diameter, d, of PS foam blown with CO2 for three different single hole dies and for the multiple hole die.

Parameter 2.0 mm die 1.0 mm die 0.50 mm die multiple hole die

ρ (kg.m-3) 30 31 31 50 φPS (kg.h-1) 9.0 3.6 0.40 7.0 d (mm) 12 6.0 3.0 20


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Figure 5.8: PS foam produced with the 2.0 mm hole die

Figure 5.9: SEM image of the PS foam produced with the 2.0 mm hole die (35x, 100x and 500x magnified)

When the die diameter was decreased to 1.0 mm, the operating pressure increased to 160 bar. The decrease in PS production to 3.6 kg/hour resulted in a decrease in torque to 5.2 Nm. The resulting PS string had a diameter of 6.0 mm and a density of 31 kg/m3 (Figure 5.10). Increasing the CO2 addition rate to a level above the maximum solubility in the polymer had no effect on the density of the polymer. The SEM pictures show that the cells have an open structure and a size of about 60 µm (Figure 5.11).




- 90 -

Starting up and operating the extruder with the 0.50 mm single hole die was difficult because small variations caused the pressure to jump over the maximum allowable pressure of 200 bar. This resulted in an automatic shut down of the process. In the stable operation regime, the operating pressure was increased to 180 bar due to the further decrease in diameter of the die. The PS production was 0.40 kg/hour and the torque was 5.7 Nm. The PS string had a diameter of 3.0 mm and a density of 31 kg/m3 (Figure 5.12) The SEM pictures show that the cells with a dimension of 40 µm have an open structure and that the foam is not completely homogeneous (Figure 5.13).



In all cases the polymer expands radially, where the diameter increases with a factor 6. Based on this radial expansion, the surface area per PS string, the number of PS strings per m2, and the production rate per m2 for full scale production of PS foam with a multiple hole die were calculated (see Table 5.3). The lower production rate for the 2.0 mm die is caused by the lower pressure drop over the die. With the same pressure drop the production rate of the 2.0 mm hole die will exceed that of the 1.0 mm hole die. Table 5.3. The calculated surface area per PS string, A, the calculated number of PS strings per m

2, n,

and the calculated production rate per m2, φout, for full scale production of PS foam with a multiple hole

die based on either of the three single hole dies.

Parameter 2.0 mm die 1.0 mm die 0.50 mm die

A (mm2) 112 28 7.0 n (m-2) 8,930 35,710 142,860 φout (ton.h-1) 80 125 60


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It should be noted that these large production rates are unrealistic for full scale production. For example, the machine with the 1.0 mm die (125 ton per hour) could supply the yearly demand of PS foam for the whole European community. Therefore, methods to decrease the production rate while keeping similar PS properties were investigated. The process variables that were investigated are temperature over the barrel and screw speed. The other process variables were kept constant, and a die diameter of 1.0 mm was used. First, the temperature was lowered in order to increase the CO2 solubility. However, as the temperature of the melt decreased below 120 °C, the density of the foam started to increase from 30 kg/m3 to 40 kg/m3. Furthermore the string became hard and thinner. This effect is caused by incomplete expansion of the melt, leaving CO2 pressure inside the foam and giving it a lower compressibility. The lower temperature of the melt together with the cooling of the expanding CO2 causes the polymer to solidify before it is fully expanded. Increasing the temperature of the melt by increasing the temperature of the elements on the barrel reversed this effect. Next, the screw speed was increased from 100 rpm to 150 rpm. The viscosity decreased because of shear thinning, resulting in an increased production rate, which was not the objective. Decreasing the screw speed to 50 rpm resulted in a pressure increase due to an increase in viscosity of the polymer melt and a lower production rate. Unfortunately, the density of the polymer foam increased to 40 kg/m3. Reason is that less CO2 dissolves into the polymer because of the higher viscosity. When the temperature was increased in order to decrease the viscosity of the polymer, the production rate and density returned to the original value. The foam structure remained similar under all conditions. Thus, it was concluded that the production rate cannot be significantly decreased by changing the temperature or screw speed. Next, we focus on the development of a multiple hole die. Based on a maximum production rate of 25 kg/h of the extruder, the maximum number of holes is 3, 8 and 60 for the 2.0 mm, 1.0 mm and 0.50 mm dies, respectively. The 1.0 mm die seems most appropriate for the construction of the multiple hole die for two reasons: (i) the amount of holes for de 0.50 mm die is inconveniently large, whereas the amount of holes for the 2.0 mm die is rather small, and (ii) the foam production with 1.0 mm die operates easily, with most of the variables in the middle of the operating range (except the pressure is on the lower side), making variation in both directions possible. However, to obtain somewhat higher pressure (so that CO2 remains supercritical) a die diameter of 0.90 mm was chosen. A multiple hole die with seven holes was constructed (see Figure 5.7). The holes had a diameter of 0.9 mm and a path length of 4.0 mm. The holes were arranged in two rows in a trigonal arrangement with 2.5 mm of space between each hole. This space distance was chosen on basis of the expected radial expansion. The radial expansion in the single hole die experiments was a factor 6, requiring a space distance of 5.0 mm between each hole for the multiple hole die. However, the expected density is higher as a result of the shorter residence time in the extruder as compared to the single hole die experiment, leaving shorter time for the dissolution of CO2. A factor 2 difference in density was assumed. Therefore, a space distance of 2.5 mm between each hole was chosen. The operating conditions of a successful multiple hole die experiment are shown in Figures 5.14 and 5.15, and are summarized in Table 5.1. The results with regard to the production rate, overall foam density and foam structure are presented in Table 5.2.


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Figure 5.14: Temperatures in the different elements (T1 to T11) for PS foaming experiments with supercritical CO2 as blowing agent for the multiple hole die experiment

Figure 5.15: Pressure at the die (p), CO2 addition rate (φCO2), screw torque as a percentage of 9 N

.m

(τ), and screw speed (ω) for PS foaming experiments with supercritical CO2 as blowing agent for the multiple hole die experiment


- 93 -

A production rate of 7.0 kg of foam per hour was achieved. The density of the string was about 50 kg/m3, which is in agreement with the assumption of a density increase by a factor 2. After extrusion the seven strings melted together and formed one large string (Figure 5.16). Figure 5.17 shows that the cell structure of the foam produced with the multiple hole die is similar to the cell structure in the single hole die experiments, with a cell size of 50 µm. On basis of these results it can be concluded that the principle of using a multiple hole die for the production of single large PS blocks with CO2 as blowing agent is proven. Larger block sizes and lower PS foam densities were not possible because of the limited capabilities of the extruder.

Figure 5.16: PS foam produced with the multiple hole die

Figure 5.17: SEM image of the PS foam produced with the multiple hole die (35x, 100x and 350x magnified)

Now a proof of principle has been obtained, the next step is to develop a commercial process for the production of large blocks of PS with a multiple hole die, where the quality of the foam meets the industrial specifications. A ram extruder with a much lower production rate would be more suitable for this purpose. A lower foam density and a better cell structure are expected at higher operating pressures (above 200 bar) and a longer mixing time. Another option to decrease the foam density is to expand the foam into a (partial) vacuum.


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5.5 Economic evaluation The market for PS foam in the Netherlands is 60,000 ton per year (≈ 3,000,000 m3 per year)2. Conventionally, this foam is produced using around 7 wt% pentane as blowing agent, which is equivalent to 4,200 ton/year1. About 40% of this pentane (= 1,700 ton/year) is burned in an afterburner, the rest of the pentane eventually ends up as emissions into the atmosphere (= 2,500 ton/year)1. This is not only cost-intensive, but also very environmentally harmful. The combustion reaction of pentane is: C5H12 + 8 O2 → 5 CO2 + 6 H2O (Eq. 5.1) This means that 5,200 ton/year CO2 is produced by burning 1,700 ton/year pentane. Additional natural gas is needed in the afterburner. However, this is not taken into account in the calculation. It is assumed that the burning of 4,200 ton/year pentane delivers enough energy for the whole process. Finally, the PS foam is conventionally stored for at least 4 weeks1, which means that a substantial continuous PS foam storage capacity of 240,000 m3 is required. Alternatively, around 4,200 ton/year CO2 can be used as a blowing agent instead. This CO2 does not need to be burned, and is simply used in the process, not produced. Energy is only required for pressurizing the CO2. One can also directly buy pressurized CO2 for low prices, because it is a waste product from other industries. In that case, no additional energy is needed. Because the CO2 price is negligible compared to the pentane price, it is not taken into account in this economic evaluation. Finally, no large storage facility is necessary, because the PS foam can be directly used. Table 5.4 shows the prices of the resources for the conventional PS foaming process with pentane and the alternative PS foaming process with supercritical CO2 as blowing agent. The main differences in variable costs for the conventional and the supercritical PS foaming process are presented in Table 5.5. Table 5.4: Prices of resources in the conventional and the supercritical PS foaming process


Pentane 400 €/ton 22 CO2 emission rights 13 €/ton 23 As can be seen from Table 5.5, the supercritical foaming process is economically more attractive than the conventional foaming process. The savings for not using pentane are not very large, only 0.60 € per m3 (= 1.8 M€/year per 3,000,000 m3/year) compared to the market price of PS foam2 of € 65,- per m3. The major driving force for implementation of this technology will be the environmental effects of reducing the pentane emissions by 2,500 ton per year and the CO2 emissions by 5,200 ton per year. Table 5.5 does not take into account the differences in investment (fixed) costs. The investment costs in the conventional process are larger because of the need for a large storage facility. This is not required in the alternative supercritical process.


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Table 5.5: Main differences in variable costs of the conventional and the supercritical PS foaming process

Amount

per year

Costs

(M€/year)

Pentane consumption (ton) 4,200 1.7 CO2 emission rights (ton) 5,200 0.1


Total 1.8

Pentane consumption (ton) 0 0 CO2 emission rights (ton) 0 0

Supercritical process

Total 0 0


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5.6 Conclusions PS foam can be produced with supercritical CO2 as blowing agent instead of the conventionally used pentane. This leads to economical as well as environmental advantages. In this work a multiple hole die for production of single large blocks of polystyrene foam with carbon dioxide as blowing agent was developed. First, single hole die experiments were carried out with different hole sizes (2.0, 1.0 and 0.50 mm). Using these single hole dies a dimensionally stable foam was produced with a density of 31 kg/m3 and an open cell structure. Depending upon the hole size, the production rate was 9.0, 3.6 or 0.40 kg/h and the foam expanded radially. Next, the hole diameter and hole distances for a newly constructed multiple hole die were chosen on basis of the radial expansion in the single hole die experiments. The multiple hole die consisted of seven holes of 0.90 mm in a trigonal arrangement. Tests with the multiple hole die showed that the seven strings could melt together forming one large string with a diameter of about 20 mm, a density of 50 kg/m3 and a open cell structure with a cell size of about 50 µm, which is similar to the foam properties of the single hole die experiments. Therefore, the concept of using a multiple hole die for the production of single large PS blocks with CO2 as blowing agent was proven. However, larger block sizes were not possible because of the limited capabilities of the extruder.


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5.7 References

1. Eaves, D. (Ed.); Handbook of Polymer Foams, Rapra: Shrewsbury, UK, 2004.

2. Stybenex, PS foam turnover: http://www.stybenex.nl/.

3. Cooper, A. I.; Polymer Synthesis and Processing using Supercritical Carbon Dioxide, J. Mater. Chem. 2000, 10 (2), 207-234.

4. Tomasko, D. L.; Li, H.; Liu, D.; Han, X.; Wingert, M. J.; Lee, L. J.; Koelling, K. W.;

A Review of CO2 Applications in the Processing of Polymers, Ind. Eng. Chem. Res. 2003, 42 (25), 6431-6456.

5. Sato, Y.; Fujiwara, K.; Takikawa, T.; Sumarno, Takishima, S.; Masuoka, H.;

Solubilities and Diffusion Coefficients of Carbon Dioxide and Nitrogen in Polypropylene, High-Density Polyethylene, and Polystyrene under High Pressures and Temperatures, Fluid Phase Equilib. 1999, 162 (1-2), 261-276.

6. Sumarno; Sato, Y.; Takishima, S.; Masuoka, H.; Production of Polystyrene

Microcellular Foam Plastics and a Comparison of Late- and Quick-Heating, J. Appl.

Polym. Sci. 2000, 77 (11), 2383-2395.

7. Alessi, P.; Cortesi, A.; Kikic, I.; Vecchione, F.; Plasticization of Polymers with Supercritical Carbon Dioxide: Experimental Determination of Glass-Transition Temperatures, J. Appl. Polym. Sci. 2003, 88 (9), 2189-2193.

8. Kwag, C.; Manke, C. W.; Gulari, E.; Effects of Dissolved Gas on Viscoelastic Scaling

and Glass Transition Temperature of Polystyrene Melts, Ind. Eng. Chem. Res. 2001, 40 (14), 3048-3052.

9. Lee, M.; Tzoganakis, C.; Park, C. B.; Effects of Supercritical CO2 on the Viscosity

and Morphology of Polymer Blends, Adv. Polym. Technol. 2000, 19 (4), 300-311.

10. Li, H.; Lee, L. J.; Tomasko, D. L.; Effect of Carbon Dioxide on the Interfacial Tension of Polymer Melts, Ind. Eng. Chem. Res. 2004, 43 (2), 509-514.

11. Park, H.; Thompson, R. B.; Lanson, N.; Tzoganakis, C.; Park, C. B.; Chen. P.; Effect

of Temperature and Pressure on Surface Tension of Polystyrene in Supercritical Carbon Dioxide, J. Phys. Chem. B 2007, 111 (15), 3859-3868.

12. Baldwin, D. F.; Park, C. B.; Suh, N. P.; An Extrusion System for the Processing of

Microcellular Polymer Sheets: Shaping and Cell Growth Control, Polym. Eng. Sci. 1996, 36 (10), 1425-1435.

13. Naguib, H. E.; Park, C. B.; Reichelt, N.; Fundamental Foaming Mechanisms

Governing the Volume Expansion of Extruded Polypropylene Foams, J. Appl. Polym.

Sci. 2004, 91 (4), 2661-2668.


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14. Zeng, C.; Han, X.; Lee, L. J.; Koelling, K. W.; Tomasko, D. L.; Polymer-Clay Nanocomposite Foams Prepared Using Carbon Dioxide, Adv. Mater. 2003, 15 (20), 1743-1747.

15. Shen, J.; Zeng, C.; Lee, L. J.; Synthesis of Polystyrene - Carbon Nanofibers

Nanocomposite Foams, Polymer 2005, 46 (14), 5218-5224.

16. Chiu, F.-C.; Lai, S.-M.; Wong, C.-M.; Chang, C. H.; Properties of Calcium Carbonate Filled and Unfilled Polystyrene Foams Prepared Using Supercritical Carbon Dioxide, J. Appl. Polym. Sci. 2006, 102 (3), 2276-2284.

17. Guo, M. C.; Peng, Y. C.; Study of Shear Nucleation Theory in Continuous

Microcellular Foam Extrusion, Polym. Test. 2003, 22 (6), 705-709.

18. Arora, K. A.; Lesser, A. J.; McCarthy, T. J.; Compressive Behavior of Microcellular Polystyrene Foams Processed in Supercritical Carbon Dioxide, Polym. Eng. Sci. 1998, 38 (12), 2055-2062.

19. Stafford, C. M.; Russell, T. P.; McCarthy, T. J.; Expansion of Polystyrene Using

Supercritical Carbon Dioxide: Effects of Molecular Weight, Polydispersity, and Low Molecular Weight Components, Macromolecules 1999, 32 (22), 7610-7616.

20. Xu, X.; Park, C. B.; Xu, D.; Pop-Iliev, R.; Effects of the Die Geometry on Cell

Nucleation of PS Foams Blown with CO2, Polym. Eng. Sci. 2003, 43 (7), 1378-1390.

21. Xu, X.; Park, C. B.; Effects of the Die Geometry on the Expansion of Polystyrene Foams Blown with Carbon Dioxide, J. Appl. Polym. Sci. 2008, 109 (5), 3329-3336.

22. Pentane market price 2009: http://au.quote.com/news/story.action;jsessionid=abcf3OR

xxQ8GBfghhmcts?id=CCN308u7710&pg=12.

23. CO2 emission rights price 2009: http://zakelijk.eneco.nl/Energievandaag/Nieuwsover-zicht/ Pages/AlleogengerichtopmarktCO2-emissierechten.aspx.

6 Extraction of cannabinoids using

supercritical carbon dioxide By: J. van Spronsen, H. Perrotin-Brunel, P. Cabeza Perez, M. J. E. van Roosmalen, G. J. Witkamp, C. J. Peters

and M. C. Kroon

___________________________________________________________________________

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6. Extraction of cannabinoids using supercritical carbon dioxide

6.1 Introduction Cannabis sativa L. (cannabis) is one of the oldest medicinal plants known1. At present, there is a growing interest in cannabis and its medicinal uses. A number of different indications for cannabis have been described, such as multiple sclerosis, glaucoma, chronic pain and the side effects of chemotherapy. The major compound from cannabis, (-)-∆9-tetrahydrocannabinol (∆9-THC), is psychoactive and has been legally registered for medical application in several countries. ∆9-THC eases pain and is neuroprotective; it has approximately equal affinity for the CB1 and CB2 receptors2. Its effects are perceived to be mostly cerebral. ∆9-THC is not the only biologically active compound in cannabis. In total cannabis contains more than 400 different ingredients, including at least 60 cannabinoids which can be biologically active3. Other common cannabinoids (besides ∆9-THC) are:

- Cannabidiol (CBD) CBD is not psychoactive, although it may modulate the euphoric effects of ∆9-THC to some extent4. Medically, it appears to relieve convulsion, inflammation, anxiety, and nausea. CBD has a greater affinity for the CB2 receptor than for the CB1 receptor. It is perceived to have more effect on the body.

- Cannabinol (CBN) CBN is the primary product of ∆9-THC degradation, and there is usually little of it in a fresh plant. CBN content increases as ∆9-THC degrades in storage, and with exposure to light and air. It is only mildly psychoactive, and is perceived to be sedative or stupefying3.

- Cannabichromene (CBC) - Cannabigerol (CBG) - Tetrahydrocannabivarin (THCV)

The structures these common cannabinoids are shown in Figure 6.1.

Figure 6.1: Structures of various cannabinoids

6. Extraction of cannabinoids using supercritical carbon dioxide ___________________________________________________________________________

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The majority of cannabinoids are present in the cannabis plant as their corresponding carboxylic acids1. For example, in Figure 6.2 the structure of (-)-∆9-tetrahydrocannabinolic acid (∆9-THC acid) and cannabidiolic acid (CBD acid) are shown. These acids are not biologically active, but can be readily converted into their corresponding biologically active neutral cannabinoids by heating. This process is called decarboxylation5.

Figure 6.2: Structures of ∆9-THC acid and CBD acid

The availability of the various cannabinoids as pure compounds is of great importance for pharmacological studies and for the development of new medicines. Since ∆9-THC and CBD are the major components, they have been isolated and produced on a larger scale (kilograms) than the other cannabinoids6. However, cannabis contains a large number of other potentially biologically active cannabinoids (in small amounts) that have not yet been studied for the pharmacological effects. The content of each cannabinoid present in cannabis differs per plant variety and also depends on the growing conditions. Generally, the ∆9-THC content (mostly in the form of ∆9-THC acid) in cannabis is around 15% to 20%7. The aim of this work is to develop a process for the isolation of the major and minor cannabinoids from cannabis in their pure form. First, the decarboxylation reaction of the carboxylic acids present in the plant into their biologically active forms is investigated8. Thereafter, the separation of the different cannabinoids is at the center of interest. This separation is difficult because of the similar structure of the different cannabinoids. So far, only selective extraction with organic solvents and chromatographic separation have been used for separation of ∆9-THC and CBD from cannabis at the laboratory scale6,9. For example, ∆9-THC can be extracted directly from cannabis by using hydrocarbons (hexane) or alcohols with a yield exceeding 90%6. However, these volatile organic solvents are flammable and many of them are toxic. Moreover, a commercial process is non-existent. Here, the extraction of cannabinoids by using supercritical carbon dioxide (CO2) as environmentally benign extractant is investigated10; volatile organic solvents are no longer needed. Supercritical CO2 has no flammability or toxicity issues, the solvent removal is simple and efficient, and the extract quality can be well-controlled. This ‘green’ solvent has been widely used to extract natural components, including pharmaceutical molecules, on a commercial scale before11-16. The solubility of the cannabinoids in supercritical CO2 is measured first in order to find feasible extraction conditions10. Thereafter, the supercritical extraction process is carried out on a pilot plant scale.


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6.2 Decarboxylation of ∆9-THC acid In the production of cannabinoids for pharmaceutical use it is necessary to convert the acids into neutral cannabinoids via a decarboxylation reaction, where the carboxyl group is split off as CO2 under heating5. The decarboxylation reaction scheme of ∆9-THC acid to ∆9-THC is shown in Figure 6.3.

O

H

HOH

OH

O

O

H

HOH

+ CO2

Figure 6.3: Decarboxylation reaction of ∆9-THC acid

This decarboxylation reaction has been studied previously, both in open and closed reactors17-

19. When performing the thermal decarboxylation of cannabinoid acids in an open reactor, an optimum temperature at which the reaction rate would be high enough and simultaneous evaporation of neutral cannabinoids would not occur could not be found17. Instead, better results were obtained using closed reactors under different conditions. Kanter et al.18 suggested to perform the decarboxylation reaction at 200 oC for 3 minutes, whereas Smith and Vaughan19 carried out the reaction at 100 oC during 60 minutes. They analyzed the conversion by measuring the concentrations of ∆9-THC acid and ∆9-THC in the cannabis before and after the reaction took place. For this, the cannabis was treated with methanol and ultrasound in order to release the cannabinoids into the methanol phase20. Thereafter, the methanol phase (as a mobile phase) was analyzed using high performance liquid chromatography (HPLC) with a C18 stationary phase18,19. However, the accuracy of these measurements was rather limited18,19. Here, the method of analysis of the concentrations of ∆9-THC acid and ∆9-THC in the cannabis before and after the decarboxylation reaction is improved in order to increase the reproducibility. Thereafter, the decarboxylation reaction of ∆9-THC acid to ∆9-THC is studied at different temperatures in a rotary evaporator (closed reactor). Kinetics parameters were also calculated from the experimental results8. 6.2.1 Improvement of sample preparation and analysis The analysis of the cannabinoids ∆9-THC acid and ∆9-THC in cannabis is optimized in order to increase the accuracy and reproducibility of the measurements. The first step to improve the reproducibility was to increase the amount of methanol in the sonication step (by a factor ten), so that subsequent dilution for the HPLC analysis was no longer required. The methanol used was HPLC reagent grade from J. T. Baker. The (medicinal) cannabis was supplied by BEDROCAN, batch nr. 01.57.260307 (10-07-2007) and contained around 18% of ∆9-THC, mostly in the form of ∆9-THC acid. This material was used without further purification. Thereafter, the influence of the most critical parameters (i.e., sonication time, amount of cannabis) on the extraction of ∆9-THC acid and ∆9-THC from the solid matrix (cannabis) with methanol as extractant was investigated. An Erlenmeyer was filled with a know amount


- 104 -

of cannabis (e.g., 200 mg), and 50 ml methanol was added. The Erlenmeyer was weighted and put in the sonication bath for 5, 10 or 15 minutes. Then, a sample was taken and analyzed using a Chromapack HPLC system consisting of an Isos pump, an injection valve and a UV-VIS detector (model 340 – Varian) at 228 nm. The system was controlled by Galaxie Chromatography software. The analytic column was a Vydac (Hesperia, CA) C18 stationary phase, type 218MS54 (4.6 x 250 mm2, 5 µm). The mobile phase consisted of a mixture of methanol, distilled water and tetrahydrofuran (v/v/v = 10/4/1). The flow rate was 1.5 ml.min-1

and the total running time was 14 minutes. The Erlenmeyer was weighted again afterwards in order to check the mass balance. The influence of sonication time on the amount of ∆9-THC acid and ∆9-THC extracted from 200 mg of cannabis using 50 ml of methanol is shown in Table 6.1. According to literature20 5 minutes should be sufficient for the sonication step, but here it is shown 5 minutes is too short. The amount of ∆9-THC acid and ∆9-THC extracted are higher at 10 and 15 minutes, indicating that not all cannabinoids have been released from the cannabis matrix in 5 minutes only. It can also be noted that a sonication time of 10 and 15 minutes leads to similar good results, which are in agreement with the cannabinoids content given by the supplier. Eventually, a sonication time of 15 minutes was chosen so that one can be sure that all cannabinoids have been released into the methanol. This would enhance the reproducibility of the measurements significantly. Table 6.1: Influence of sonication time on the amount of ∆9-THC and ∆9-THC acid extracted (% of cannabis) from 200 mg of cannabis using 50 ml of methanol

Time (min) ∆9-THC (%) ∆9-THC acid (%) Total (%)

5 6.16 10.29 16.45 10 7.05 12.10 19.15 15 6.89 11.32 18.21

The influence of the amount of cannabis on the reproducibility is investigated next. For this reason, the extraction with methanol (50 ml) of 200 mg of cannabis and 400 mg of cannabis after 15 minutes of sonication time was repeated five times. Figure 6.4 shows the influence of the amount of cannabis on the amount of ∆9-THC acid and ∆9-THC extracted for five different experiments. It is observed that the samples consisting of 400 mg of cannabis result in a higher reproducibility than the samples with 200 mg cannabis. The reason is that the cannabis sample is not completely homogeneous, resulting in higher variations of the amount of cannabinoids extracted when the sample is relatively small. Therefore, an amount of 400 mg of cannabis was chosen for the analysis of the decarboxylation reaction.


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0

5

10

15

20

0 1 2 3 4 5Number of experiment (-)

% E

xtr

ac

ted THCA 400 mg

THCA 200 mg

THC 400 mg

THC 200 mg

Figure 6.4: Influence of amount of cannabis (200 mg versus 400 mg) on the amount of ∆9-THC acid and ∆9-THC extracted (% of cannabis) using 50 ml of methanol. The experiments are five times repeated in order to investigate the reproducibility.

Finally, also larger amounts of cannabis (600 mg, 800 mg and 1.00 g) were extracted with 50 ml of methanol, in order to see if the methanol is not saturated with cannabinoids. In that case, the extraction could be mass transfer limited. Figure 6.5 shows the mass of ∆9-THC acid and ∆9-THC extracted from 200 mg, 400 mg, 600 mg, 800 mg and 1.00 g of cannabis using 50 ml of methanol and 15 minutes of sonication time. This figure shows that the relationship between the amount of cannabis in the sample and the amount of cannabinoids extracted is linear, so the extraction is not mass transfer limited. It shows that the method developed to analyze the amount of ∆9-THC acid and ∆9-THC in cannabis is robust and has a high reproducibility.

R2 = 0.9936

R2 = 0.9641

0

50

100

150

200

0.0 0.2 0.4 0.6 0.8 1.0

Mass cannabis (g)

Mass e

xtr

acte

d (

mg

)

THC

THCA

Figure 6.5: Influence of amount of cannabis (200 mg, 400 mg, 600 mg, 800 mg and 1.00 g) on the amount of ∆9-THC acid and ∆9-THC extracted (mg) using 50 ml of methanol. The linear correlation coefficients are close to 1.


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6.2.2 Decarboxylation reaction and kinetics The decarboxylation reaction of ∆9-THC acid to ∆9-THC is studied at different temperatures (100oC, 110 oC, 120 oC, 130 oC, 140 oC) in a rotary evaporator (Figure 6.6). First, the cannabis was blended with a mixer. Next, 400 mg of blended cannabis was put into the rotary evaporator, in which it was heated to the desired temperature under vacuum. Samples were taken at several times during the decarboxylation reaction in order to determine the kinetics of the reaction. The content of ∆9-THC acid and ∆9-THC in each sample was measured by extraction with 50 ml of methanol after 15 minutes of sonication time, followed by HPLC analysis of the methanol phase (as described in paragraph 6.2.1).

Figure 6.6: Rotary evaporator used to study the decarboxylation of ∆9-THC acid

The results for the decarboxylation reaction are presented in Figure 6.7. It can be seen that the ∆9-THC acid can be completely converted to ∆9-THC, without any ∆9-THC degradation at higher temperatures. The reaction rate can be increased by increasing the temperature.

0

20

40

60

80

100

0 25 50 75 100 125 150 175 200

Time (min)

% T

HC

A d

ecarb

oxyla

ted

140 C

130 C

120 C

110 C

100 C

Figure 6.7: Conversion (% ∆9-THC acid decarboxylated) versus time at different temperatures for the decarboxylation reaction of ∆9-THC acid to ∆9-THC


- 107 -

It is expected that the decarboxylation reaction is a first order reaction. Therefore, a linear relationship between the natural logarithm of the ∆9-THC acid concentration (CTHCA) and time (t) is expected:

ktCC THCATHCA −= )ln()ln( 0, (Eq. 6.1)

where CTHCA,0 is the ∆9-THC acid concentration at the time t = 0, and k is the first order rate constant. Figure 6.8 shows the plot of the ln(CTHCA) versus t. A linear relationship is observed, indicating that the decarboxylation reaction is indeed a first order reaction.

-8

-6

-4

-2

0

0 50 100 150 200

t (min)

ln (

CT

HC

A)

140 C

130 C

120 C

110 C

100 C

Figure 6.8: Plot of the natural logarithm of the ∆9-THC acid concentration versus the time

The value for the rate constant k at the different temperatures T can now be obtained from the slopes in Figure 6.8. Table 6.2 presents the values for k as a function of T. Table 6.2: Values for the rate constant (k) at different temperatures (T)

T (oC) k (min

-1)

100 0.0285 110 0.0649 120 0.1220 130 0.2176 140 0.4008

Generally, the Arrhenius equation is a simple but remarkable accurate formula for the temperature dependence of the rate constant:

−⋅=

RT

EAk aexp (Eq. 6.2)

where A is the pre-exponential factor, Ea is the activation energy, and R is the gas constant.


- 108 -

The activation energy can thus be obtained from the slope of a plot of the natural logarithm of the rate constant versus the reciprocal temperature according to:

⋅−=TR

EAk a 1

)ln()ln( (Eq. 6.3)

Figure 6.9 presents the plot of ln(k) versus (1/T). The activation energy of the decarboxylation of ∆9-THC acid can be obtained from the slope and is found to be: Ea = 84.8 kJ/mol. The pre-exponential factor is obtained from the intercept: A = 3.69.108 s-1.

y = -10200x + 19.726

R2 = 0.9947

-10

-8

-6

-4

-2

0

0.0024 0.0025 0.0026 0.0027

1/T

ln(k

)

Figure 6.9: Plot of the natural logarithm of the rate constant versus the reciprocal temperature

This activation energy is relatively low compared to the activation energy of the decarboxylation of benzoic acid (~250 kJ/mol),21 which might be due to the mesomeric effect of the oxygens connected to the benzyl ring in ∆9-THC acid. This is consistent with the lower activation energy of 90-97 kJ/mol observed previously for the decarboxylation of OH-substituted benzoic acid derivates21. Because the relationship between ln(k) and (1/T) is linear, it is expected that there are no ∆9-THC acid and ∆9-THC losses at higher temperatures by evaporation or degradation. It is therefore interesting to measure if any weight loss of the cannabis does occur during heating. For this, a sample of around 1 gram of cannabis was weighted and heated at the desired temperature (90oC, 110oC and 120oC) in the rotary evaporator under vacuum for up to 4 hours. The sample was weighted every 10-30 minutes. Figure 6.10 depicts the weight loss of cannabis at different temperatures. It can be noticed that the weight loss of the cannabis during heating is substantial, especially at higher temperatures. Because it is not likely that ∆9-THC acid is lost (because of the linear relationship between ln(k) and (1/T)), it is expected that these evaporative losses mainly consist of water and other low boiling compounds such as ethereal oils and terpenes.


- 109 -

0

5

10

15

20

25

0 20 40 60 80 100 120 140

time (min)

% l

os

s120 C

110 C

90 C

Figure 6.10: Weight loss of cannabis over time (by evaporation) as a function of temperature

It can be concluded that it is possible to transform ∆9-THC acid to ∆9-THC by heating cannabis under vacuum. The heating produces the energy required to activate the decarboxylation reaction (84.8 kJ/mol). The temperature effects the time needed to reach full conversion. At low temperatures (90 oC), the time to reach full conversion is high. At higher temperatures (140 oC), the reaction is faster but considerable weight losses occur, mainly due to the loss of terpenes and other low boiling compounds by evaporation. Because the ∆9-THC does not seem to evaporate, it is better to use higher temperatures (140 oC) for the decarboxylation reaction. At these temperatures the reaction rate is not only higher, but the low boiling compounds also have been removed, so that they cannot contaminate the ∆9-THC in the next extraction step. It is likely that less purification steps are needed after the decarboxylation reaction step.


- 110 -

6.3 Solubility of ∆∆∆∆9-THC in supercritical CO2 In order to use supercritical CO2 as environmentally benign solvent for the extraction of ∆9-THC (and other cannabinoids) from cannabis, the solubility of ∆9-THC in supercritical CO2 has to be known. However, solubility data are lacking in literature. Therefore, in this work the solubility of ∆9-THC in supercritical CO2 has been determined10. The solubility measurements were carried out using the solubility cell set-up, which is depicted schematically in Figure 6.11. A picture of the set-up is shown in Figure 6.12.

Figure 6.11: Schematic of the solubility cell set-up

The apparatus was designed to perform experiments using pressures up to 35 MPa and temperatures in the range of 293 to 423 K. The solubility cell was composed of a sample vessel made of stainless steel, a micro pump (Micropump INC, model 380) to circulate the CO2, a pressure sensor (EFE – type VLE 700) with an accuracy of 0.05 MPa and a thermocouple PT-100 with an accuracy of 0.1 K. All the components were placed in an oven (Memmert – type VLE 700) to keep the temperature constant. The system loop contained an HPLC to measure the concentration of the dissolved ∆9-THC in CO2. The Chromapack HPLC system consisted of an Isos pump, an injection valve and a UV-VIS detector (model 340 – Varian) at 228 nm. The system was controlled by Galaxie Chromatography software. The analytic column was a Vydac (Hesperia, CA) C18 stationary phase, type 218MS54 (4.6 x 250 mm2, 5 µm). The mobile phase consisted of a mixture of methanol, distilled water and tetrahydrofuran (v/v/v = 10/4/1). The flow rate was 1.5 ml.min-1

and the total running time was 14 minutes. All the tubing was isolated to minimize heat losses. A back pressure regulator was placed at the end of the HPLC to ensure a maximum pressure decrease in the system of less than 0.2% due to volume losses when a sample was taken. The internal volume in which the sample and CO2 circulated was about 8 ml.


- 111 -

Figure 6.12: Experimental set-up with solubility cell

The CO2 was purchased from HoekLoos and had a purity of 99.97%. The methanol and tetrahydrofuran used were HPLC reagent grade from J. T. Baker. ∆9-THC with purity higher than 96.5% was kindly donated by Echo Pharmaceuticals B.V, Weesp, the Netherlands. The material was used without further purification. ∆9-THC is a highly viscous liquid and was therefore first dissolved in methanol before transferring into the sample cylinder. Thereafter, the methanol was completely evaporated with a vacuum pump (RNF Lab) during one hour. Subsequently, the pump was disconnected and the system, containing only pure ∆9-THC, was closed. After the system was closed, the oven was set at the desired temperature. After the preset temperature had been reached, the system was filled with CO2 until the desired pressure was reached. When the conditions were stable, the CO2 circulation over the sample vessel was started. A sample for HPLC analysis was taken after 2 hours and successively every 30 minutes. When the concentration difference measured was less than 0.09x10-4

between two subsequent analyses, with a pressure and temperature differences less than 0.05 MPa and 0.2 K respectively, it was assumed that equilibrium was reached, and the concentration measured was recorded as the solubility. The experimental solubility data of ∆9-THC in supercritical CO2 are shown in Table 6.3. The maximum standard deviation was 0.0015x10-4 (in mole fraction). The lowest measured solubility was 0.20x10-4 (in mole fraction) at 315 K and 13.2 MPa. Below this pressure and/or temperature, the solubility was too low to be measured accurately. The isotherms are presented graphically in Figure 6.13. It can be noticed that the ∆9-THC solubility in CO2 increases with pressure. At constant pressure, two observations can be made: (i) at pressures lower than approx. 15 MPa, the solubility decreases with increasing temperature; (ii) at pressures higher than approx. 15 MPa, there is a reverse tendency i.e., a higher temperature is accompanied by a higher solubility. This particular pressure region has been reported as the crossover region i.e., the crossing of solubility lines22. This behavior has been observed before with several drug components23.


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Table 6.3: Solubility of ∆9-THC in supercritical CO2 at different conditions

T = 315 K T = 327 K T = 335 K T = 345 K p /

MPa y / - x10-4

error / - x10-4

p / MPa

y / - x10-4

error / - x10-4

p / MPa

y / - x10-4

error / - x10-4

p / MPa

y / - x10-4

error / - x10-4

13.2 0.20 ± 0.01 14.0 0.33 ± 0.02 13.7 0.32 ± 0.02 14.6 0.98 ± 0.05 19.4 0.65 ± 0.03 14.1 0.35 ± 0.02 15.4 0.72 ± 0.04 17.9 1.59 ± 0.08 20.3 0.65 ± 0.03 14.8 0.45 ± 0.02 17.8 1.57 ± 0.08 20.7 2.09 ± 0.10 23.0 0.69 ± 0.03 15.1 0.57 ± 0.03 20.0 1.69 ± 0.08 22.0 2.95 ± 0.15 25.1 0.83 ± 0.04 15.4 0.56 ± 0.03 22.1 2.33 ± 0.12

15.8 0.45 ± 0.02 23.3 2.78 ± 0.14 16.3 0.65 ± 0.03 16.8 0.69 ± 0.03 17.6 0.68 ± 0.03 17.8 0.71 ± 0.04 18.2 0.68 ± 0.03 20.0 1.35 ± 0.07 22.0 1.42 ± 0.07 23.5 1.99 ± 0.10

It can be concluded that for feasible extraction e.g., where the solubility of ∆9-THC in supercritical CO2 is higher than 1x10-4 (in mole fraction), the pressure should be above about 20 MPa and the temperature should be higher than 325 K.

Figure 6.13: ∆9-THC solubility in supercritical CO2


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6.4 Supercritical extraction of cannabinoids from cannabis The extraction of ∆9-THC using supercritical CO2 as extracting solvent is studied next on a pilot plant scale in order to determine the optimum operating conditions for the highest extraction yield and quality of the product. The pressure, temperature, CO2 flow rate and extraction time are varied. Figure 6.14 shows the schematic of the pilot plant for the cannabinoids extraction with supercritical CO2. First, the cooling and heating system are switched on, and set to the desired temperature. Next, the extraction vessel is opened and filled with around 45 g of decarboxylated cannabis with a THC content of around 13%. After closing, the CO2 is continuously pumped (flow rate is 6 kg/h) from the storage vessel into the extraction vessel, which is kept at the required temperature by using a heating jacket. At the moment that the desired pressure is reached, the pressure transducer starts controlling the CO2 flow into the separator. The separator operates at higher temperature (85 oC) in order to evaporate the CO2 (the CO2 is no longer supercritical but gaseous) and to obtain the extracted material. Via a condenser the CO2 is recycled to the storage vessel. It is possible to take samples out of the separator during the extraction. Afterwards, the extract is weighted and analyzed. Also, the remaining residue was weighted in order to check the mass balance. A picture of the pilot plant is shown in Figure 6.15.

Figure 6.14: Schematic of the experiment set-up for the supercritical extraction of cannabis

The results of the ∆9-THC using supercritical CO2 are presented in Table 6.4. In all cases, an extraction efficiency of over 50% was achieved. It can be noticed that the highest quality of the product is obtained at the highest pressures, because the ∆9-THC content of the extract is highest at 230 bar. This is consistent with the higher solubility of ∆9-THC in supercritical CO2 at higher pressure (see paragraph 6.3).


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Figure 6.15: Pilot scale set-up for the supercritical cannabinoids extraction

Table 6.4: The effect of pressure (p), temperature (T) and time (t) on the extraction efficiency (η) and on the product quality as expressed by the THC content of the extract (xTHC,out). Moreover, the total amount of extract (mout), the starting amount of cannabis (min) and the starting THC content (xTHC,in) of the cannabis are given.

p / bar T / oC t / min min / g xTHC,in / % mout / g xTHC,out / % η / %

150 40 127 44.9 13.0 17.4 24.7 73.9 200 40 180 47.9 15.7 10.2 46.6 63.1 230 40 180 47.5 13.0 11.0 51.1 91.4 150 50 195 44.2 12.6 9.5 41.8 71.4 200 50 180 44.4 13.3 8.2 37.7 52.5 230 50 180 45.5 14.7 9.5 47.9 67.8

Another conclusion is that the ∆9-THC content of the product is around 50%, which is far too low for direct use in a pharmaceutical product where a ∆9-THC content of >95% is required. This means that an additional purification step is always required to obtain a pharmaceutical quality. Conventionally, a column separation using hexane as solvent is performed. Options for an organic solvent free separation step are supercritical fractionation and supercritical centrifugal partition chromatography, which have to be investigated next. Another interesting option is supercritical countercurrent extraction. The solid product, however, has to be dissolved in a solvent that is not soluble in CO2. For this purpose an ionic liquid as alternative solvent can be chosen, which is explained in more detail in the next two chapters.


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6.5 Economic evaluation The economical and environmental impact of replacing hexane by supercritical CO2 as a solvent for the production of cannabinoids is small. Reason is that the cost of production of the active ingredient is negligible with respect to the price of the product. Another reason is that the market is relatively small. The current market for medicinal marihuana in the Netherlands is only 500 kg per year for around 10.000 consumers (50 g per person per year)24 with a total turnover of around 3.0 M€ per year (€ 6 per gram). Moreover, this cannabis is smoked directly instead of isolating the pure cannabinoids. The environmental savings by using supercritical CO2 for isolation are therefore minimal. However, the supercritical process is still interesting for developing a alternative dosage form of ∆9-THC (pil) that does not involve smoking. The potential market for such a medicine is much larger, because many medicinal consumers buy marihuana from other sources. Moreover, it is important to develop new environmentally benign isolation and purification methods for new products (such as ∆9-THC in tablet form) in the pharmaceutical industry, which can be directly applied. Once a method is chosen, it is virtually impossible to change it because of the registration costs.


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6.6 Conclusions A two-step process for the production of ∆9-THC from cannabis is developed. In the first step the acidic form of ∆9-THC is decarboxylated under vacuum at higher temperatures. It was found that full conversion can be achieved at temperatures above 100 oC within 2 hours. The experimental results are in full agreement with a first order reaction. The second step involves the extraction of ∆9-THC from the decarboxylated cannabis using supercritical CO2 as extractant. The solubility of ∆9-THC increases with pressure, and also increases with temperature at pressure higher than 15 MPa. Therefore, supercritical CO2 extraction is economically feasible above 15 MPa. Subsequent extractions at the pilot scale showed that the extract contained about 50% of ∆9-THC. The highest quality was achieved at the highest pressures. For a pharmaceutical quality, the product has to be further purified. The economic impact of the new process for the production of ∆9-THCis negligible. However, the newly developed process is a good example for introducing environmentally benign processes into the pharmaceutical industry.


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6.7 References

1. Zuardi, A. W.; History of Cannabis as a Medicine: A Review, Rev. Bras. Psiquiatr. 2006, 28 (2), 153-157.

2. Thomas, A.; Stevenson, L. A.; Wease, K. N.; Price, M. R.; Baillie, G.; Ross, R. A.;

Pertwee, R. G.; Evidence that the Plant Cannabinoid ∆9-Tetrahydrocannabivarin is a Cannabinoid CB1 and CB2 Receptor Antagonist, Brit. J. Pharmacol. 2007, 146 (7), 917–926.

3. Williamson, E. M.; Evans, F. J.; Cannabinoids in Clinical Practice, Drugs 2000, 60

(6), 1303-1314.

4. Ilan, A. B.; Gevins, A.; Coleman, M.; ElSohly, M. A.; De Wit, H.; Neurophysiological and Subjective Profile of Marijuana with Varying Concentrations of Cannabinoids, Behav. Pharmacol. 2005, 16 (5-6), 487-496.

5. Grotenhermen, F.; Russo, E., Eds. Cannabis and Cannabinoids: Pharmacology,

Toxicology, and Therapeutic Potential; Routledge: London, UK, 2002.

6. Hazekamp, A.; Simons, R.; Peltenburg-Looman, A.; Sengers, M.; Van Zweden, R.; Verpoorte, R.; Preparative Isolation of Cannabinoids from Cannabis Sativa by Centrifugal Partition Chromatography, J. Liq. Chrom. Rel. Technol. 2004, 27 (15), 2421-2439.

7. Huestis, M. A.; Sampson, A. H.; Holicky, B. J.; Henningfield, J. E.; Cone, E. J.;

Characterization of the Absorption Phase of Marijuana Smoking, Clin. Pharmacol.

Ther. 1992, 52 (1), 31-41.

8. Cabeza Perez, P.; Cannabis Isolation: I. Decarboxylation, II. Solubility of

Tetrahydrocannabinol in Supercritical Carbon Dioxide; MSc Thesis Delft University of Technology: Delft, Netherlands, 2009.

9. Choi, Y. H.; Hazekamp, A.; Peltenburg-Looman, A. M. G.; Frederich, M.; Erkelens,

C.; Lefeber, A. W. M.; Verpoorte, R.; NMR Assignment of Major Cannabinoids and Cannabiflavonoids Isolated from Cannabis Sativa Flowers, Phytochem. Anal. 2004, 15

(6), 345-354.

10. Perrotin-Brunel, H.; Cabeza Perez, P.; Van Roosmalen, M. J. E.; Van Spronsen, J.; Witkamp, G. J.; Peters, C. J.; Solubility of ∆9-Tetrahydrocannabinol in Supercritical Carbon Dioxide: Experiments and Modeling, Accepted for publication in J. Supercrit.

Fluids 2009.

11. Mendes, R. L.; Reis, A. D.; Pereira, A. P.; Cardoso, M. T.; Palavra, A. F.; Coelho, J. P.; Supercritical CO2 Extraction of γ-Linolenic Acid (GLA) from the Cyanobacterium Arthrospira (Spirulina)maxima: Experiments and Modeling, Chem. Eng. J. 2005, 105

(3), 147-152.

12. Reverchon, E.; Supercritical Fluid Extraction and Fractionation of Essential Oils and Related Products, J. Supercrit. Fluids 1997, 10 (1), 1-37.


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13. Reverchon, E.; De Marco, I.; Supercritical Fluid Extraction and Fractionation of

Natural Matter, J. Supercrit. Fluids 2006, 38 (2), 146-166.

14. Sovová, H.; Mathematical Model for Supercritical Fluid Extraction of Natural Products and Extraction Curve Evaluation, J. Supercrit. Fluids 2005, 33 (1), 35-52.

15. Sovová, H.; Sajfrtová, M.; Bártlová, M.; Opletal, L.; Near-Critical Extraction of

Pigments and Oleoresin from Stinging Nettle Leaves, J. Supercrit. Fluids 2004, 30

(2), 213-224.

16. Zizovic, I.; Stamenić, M.; Orlović, A.; Skala, D.; Supercritical Carbon Dioxide Extraction of Essential Oils from Plants with Secretory Ducts: Mathematical Modeling on the Micro-Scale, J. Supercrit. Fluids 2007, 39 (3), 338-346.

17. Veress, T.; Szanto, J. I.; Leisztner, L.; Determination of Cannabinoid Acids by High-

Performance Liquid Chromatography of Their Neutral Derivatives Formed by Thermal Decarboxylation: I. Study of the Decarboxylation Process in Open Reactors, J. Chromatogr. A 1990, 520, 339-347.

18. Kanter, S. L.; Musumeci, M. R.; Hollister, L. E.; Quantitative Determination of ∆9-

Tetrahydrocannabinol and ∆9-Tetrahydrocannabinolic Acid in Marihuana by High-Pressure Liquid Chromatography, J. Chromatogr. A, 1979, 171, 504-508.

19. Smith, R. N.; Vaughan, C. G.; High-Pressure Liquid Chromatography of Cannabis:

Quantitative Analysis of Acidic and Neutral Cannabinoids, J. Chromatogr. A, 1976, 129, 347-354.

20. Hazekamp, A.; Cannabis; Extracting the Medicine, Dissertation Leiden University:

Leiden, Netherlands, 2007.

21. Li, J.; Brill, T. B.; Spectroscopy of Hydrothermal Reactions 23: The Effect of OH Substitution on the Rates and Mechanisms of Decarboxylation of Benzoic Acid, J.

Phys. Chem. A 2003, 107 (15), 2667–2673.

22. Foster, N. R.; Gurdial, G. S.; Yun, J. S. L.; Liong, K. K.; Tilly K. D.; Ting, S. S. T.; Singh, H.; Lee, J. H.; Significance of the Crossover Pressure in Solid-Supercritical Fluid Phase Equilibria, Ind. Eng. Chem. Res. 1991, 30 (8), 1955-1964.

23. Yamini, Y.; Arab, J.; Asghari-khiavi, M.; Solubilities of Phenazopyridine,

Propranolol, and Methimazole in Supercritical Carbon Dioxide, J. Pharm. Biomed.

Anal. 2003, 32 (1), 181-187.

24. Van der Ham, B.; Initiatiefnota Toegankelijker medicinale cannnabis, September 2009: http://www.d66.nl/d66nl/document/initiatiefnota_medicinale_cannabis/f=/vi91h vfx537d.pdf

7 Catalysis and separations using ionic liquids

and carbon dioxide By: J. van Spronsen, M. C. Kroon, E. Kühne, C. J. Peters, G. J. Witkamp, B. Breure, A. Shariati, L. J. Florusse,

V. A. Toussaint, K. E. Gutkowski, M. Costantini, R. A. Sheldon, I. W. C. E. Arends, M. A. Tavares Cardoso and

W. de Jong

___________________________________________________________________________

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7. Catalysis and separations using ionic liquids and carbon dioxide

7.1 Introduction Both ionic liquids and supercritical carbon dioxide (CO2) have been described as alternative ‘green’ solvents, but their properties are very different. Ionic liquids are non-volatile but highly polar compounds1, whereas supercritical CO2 is an apolar but highly volatile compound2. The combination of these two solvents has some unique features. It has been discovered that supercritical CO2 is highly soluble in ionic liquids, while the solubility of ionic liquids in supercritical CO2 is negligibly low3-5. Figure 7.1 shows this remarkable phase behavior of ionic liquid + CO2 systems.

Figure 7.1: Phase behavior of binary ionic liquid + CO2 systems

On basis of this phase behavior, it was suggested to use supercritical CO2 as extractant for hydrophobic substances from ionic liquids4. These hydrophobic substances can be recovered without any contamination by the ionic liquid, because ionic liquids just do not dissolve in the supercritical CO2. Combined with the fact that ionic liquids are excellent reaction media for catalyzed reactions (i.e., good tunable solubility characteristics, high reactivity and high selectivity), this led to the development of chemical processes, where the reaction was carried out in the ionic liquid and the product was extracted afterwards with supercritical CO2

4,6,7. An example of this chemical process set-up is the asymmetric hydrogenation of tiglic acid in the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) with a dissolved ruthenium catalyst with high conversion and enantioselectivity6 (see Figure 7.2). After the reaction, the product (R)-2-methylbutanoic acid was extracted from the ionic liquid with supercritical CO2 giving clean separation of product and catalyst. The catalyst/ionic liquid solution was then reused repeatedly without significant loss of enantioselectivity or conversion. Disadvantages of this chemical process method are the low extraction rate due to mass transfer limitations at the liquid-vapor interface, and the fact that this process is operated batch-wise.

0

10

20

30

40

50

60

70

80

0.0 0.2 0.4 0.6 0.8 1.0

xCO2, yCO2 (-)

p (

MP

a)

h

x

y

7. Catalysis and separations using ionic liquids and carbon dioxide ___________________________________________________________________________

- 122 -

COOH COOH

H+ H2 Ru-catalyst

[bmim][PF6]

Figure 7.2: Asymmetric hydrogenation of tiglic acid in the ionic liquid [bmim][PF6], where the product is extracted afterwards with supercritical CO2

6

It was found that continuous operation could be achieved when using ionic liquid/ supercritical CO2 biphasic systems as combined reaction and separation media8-23, where the CO2 phase acts both as reactant and product reservoir (see Figure 7.3) The reactants are transported into the reactor using supercritical CO2 as the mobile phase. In the reactor, the reactants dissolve in the ionic liquid phase with immobilized catalyst, where the catalyzed reaction takes place. The products are continuously extracted with the supercritical CO2 stream. The product and CO2 are separated downstream by controlled density reduction via pressure release or temperature increase. This method has been applied to hydrogenations8,9, hydroformylations10-13, dimerizations14, (enzyme-catalyzed) esterifications15-20, and the synthesis of cyclic carbonates (as CO2 fixation method)21-23.

mixer

Reactants

Carbon dioxide

Ionic liquid + catalyst phase

Carbon dioxide

phase

P ↓ V

Products

L/Smixer

Reactants

Carbon dioxide

Ionic liquid + catalyst phase

Carbon dioxide

phase

P ↓ V

Products

L/S

Figure 7.3: Continuous-flow operation in biphasic ionic liquid + supercritical CO2 systems

8-23

The continuous operation described has the disadvantage of being biphasic. This results in low reaction and separation rates due to mass transfer limitations7. In order to achieve higher reaction rates, it is desirable to create a homogeneous liquid phase during the catalyzed reaction step. In addition, instantaneous demixing into two phases, where the product is recovered from the phase that does not contain any ionic liquid or catalyst, is desirable for a fast separation. In the next paragraph, a novel process that combines such features is presented.


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7.2 Novel process for combining catalyzed reactions and separations using

ionic liquids and CO2 In this paragraph a new and general type of process for the chemical industry is presented, where the CO2 pressure controls the miscibility of reactants, products and catalyst and ionic liquid, enabling fast atom-efficient reactions in a homogenous phase, followed by product recovery in the biphasic system24,25. High reaction and separation rates can be achieved compared with the conventional fully biphasic alternative. This novel process is based on the recently established miscibility windows phenomenon: two or more immiscible phases can be forced into one homogeneous phase in the presence of compressed CO2

26-28. The miscibility switch phenomenon is schematically depicted in Figure 7.4.

Figure 7.4: Miscibility switch phenomenon: at high CO2 pressures a homogeneous liquid phase is formed, whereas at lower CO2 pressures two immiscible phases are present

25

The atom-efficient reaction is carried out in the homogeneous system (~ 10–15 MPa), where the reactants as well as the catalyst dissolve in the ionic liquid24,25. The advantage of using an ionic liquid as reaction medium is that immobilized catalyst is stabilized against oxidation by the ionic liquid, resulting in a longer lifetime of the catalyst without the need of regeneration9. The advantage of adding CO2 to the reaction mixture is that the solubility of many reactants is increased (higher concentrations) and/or that reactants, which are normally immiscible with pure ionic liquid, can dissolve in ionic liquid + CO2 mixtures (= co-solvency effect)26,27. Therefore, it is possible to bring all components in high concentrations into one homogeneous phase. In this homogeneous system, the reaction takes place without any mass transfer limitations, which results in a high reaction rate. Moreover, the addition of CO2 to the reaction mixture leads to a lower viscosity of the reaction system and a higher diffusion rate of the reactants, resulting in a further increase in reaction rate29. The ionic liquid hardly expands when CO2 is dissolved, because the CO2 molecules occupy the cavities in the ionic liquid phase30. Therefore, the reaction volume can be kept small, leading to a small equipment size. The separation is carried out in the biphasic system (~ 8–12 MPa). Application of the miscibility switch (pressure release) results in the instantaneous formation of a second phase out of the homogeneous liquid system (spinodal demixing)24,25. The light phase consists of


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supercritical CO2 with dissolved products (and reactants in case of incomplete conversion), but does not contain any ionic liquid, because CO2 cannot dissolve ionic liquid3,4. The heavy phase consists of ionic liquid with dissolved catalyst and some remaining products (and some remaining reactants in case of incomplete conversion). These phases can be separated from each other, and the pressure of the light phase is further decreased, leading to precipitation of the product (as a liquid or as a solid) out of the CO2. In this way, pure product is obtained without any detectable ionic liquid or catalyst (and no reactants when the reaction is complete)24,25. The catalyst remains in the ionic liquid phase and can be easily recycled, without negatively affecting the activity and enantioselectivity6. Also, the CO2 can be recompressed and reused. The essential advantage of using instantaneous demixing instead of conventional extraction with CO2 is the higher rate of product separation from the ionic liquid (no mass transfer limitations)24,25. Another advantage of carrying out the separation in the biphasic system is that the energy-consumption is low. Energy is only required for recompressing the CO2, but no energy-intensive distillation step is needed. Compared to the conventional separation processes, the energy consumption in the novel process set-up can be decreased by 50-80%24,25. The novel process set-up in which reactions and separations are combined using ionic liquids and supercritical CO2 as solvents is schematically shown in Figure 7.525. Since the principle of miscibility windows is a general phenomenon26,27, it is likely that the new process set-up is applicable to many industrial processes. In the next paragraphs, the novel process set-up is (partly) applied to an hydrogenation, an oxidation, a nucleophilic substitution and a hydrolysis reaction. First, the synthesis of the ionic liquids used in this work is addressed.

Figure 7.5: Novel process set-up

25. At high pressure the reaction is carried out in a homogeneous

phase (complete conversion is assumed). The product is separated from the ionic liquid in the biphasic system that is formed at lower CO2 pressure. Finally, the product is separated from the CO2 by further pressure release.

SeparationReaction

Products

Reactants

Carbon dioxide

Ionic liquid + catalyst

P ↓P ↓

P ↑

SeparationReaction

Products

Reactants

Carbon dioxide

Ionic liquid + catalyst

P ↓P ↓

P ↑


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7.3 Synthesis of the ionic liquids 7.3.1 Synthesis of 1-butyl-3-methylimidazolium tetrafluoroborate The ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) was prepared by a reaction of 1-methylimidazole and 1-chlorobutane yielding 1-butyl-3-methylimidazolium chloride ([bmim][Cl]) and followed by ion exchange with sodium tetrafluoroborate in the solvent dichloromethane31. The two-steps preparation is shown in Figure 7.6. All starting materials were bought from Sigma-Aldrich with purities over 99.5%.

Figure 7.6: Preparation of [bmim][BF4]

1-Methyl-imidazole (628.3 g; 7.652 mole) and an excess of 1-chlorobutane (837.6 g; 9.048 mole) reacted together in a 2 liter round-bottom flask fitted with a reflux condenser under heating and stirring at 80 °C for 5 days under a nitrogen atmosphere31 (see Figure 7.7). The excess of 1-chlorobutane was removed by rotary evaporation yielding [bmim][Cl] (1314.6 g; 7.526 mole) as a yellow-orange viscous liquid (conversion = 98.4 %).

Figure 7.7: Experimental set-up for the preparation of [bmim][Cl] from 1-methylimidazole and butyl chloride

NNCl

N+

N

Cl

+

N+

N

Cl

N+

N+ NaBF4CH2Cl2

BF4-

+ NaCl


- 126 -

Next, the chloride ion was exchanged for the tetrafluoroborate ion by dissolving the [bmim][Cl] (1314.6 g; 7.526 mole) in 6.0 liter dichloromethane, adding an excess of sodium tetrafluoroborate (879.8 g; 8.013 mole) crystals and stirring the mixture for 20 hours at room temperature31 (see Figure 7.8). The mixture was filtered to remove the formed sodium chloride crystals. The solvent dichloromethane was evaporated by rotary evaporation yielding [bmim][BF4] (1677.1 g ; 7.420 mole) as a yellow-orange liquid (conversion = 98.6 %).

Figure 7.8: Experimental set-up for the preparation of [bmim][BF4] from [bmim][Cl] and sodium tetrafluoroborate The purity of the resulting ionic liquid was measured to be >99.5% using boron analysis and NMR analysis. An Inductively Coupled Plasma Atomic Emission Spectroscope (ICP-AES) from Spectro, type Spectroflame, was used to measure the boron content: 4.76 ± 0.10 mol% (theoretical amount is 4.78 mol%). Nuclear magnetic resonance (NMR) equipment from Varian, type Unity Inova 300 s, was used for the NMR analysis: 1H NMR (300.2 MHz, CDCl3, TMS): δ0.93 (t, 3H), 1.34 (m, 2H), 1.86 (m, 2H), 3.95 (s, 3H), 4.20 (t, 2H), 7.47 (s, 2H), 8.71 (s, 1H), which agreed to literature data31. The amount of chloride in the ionic liquid was measured with ion chromatography from Dionex, type DX-120, and was 60 ppm. The largest impurity was fluoride, with an amount of 230 ppm. Prior to use, the [bmim][BF4] was dried under vacuum conditions at room temperature for several days. The water content of the dried ionic liquid was measured using Karl-Fischer moisture analysis from Metrohm, type 756 KF Coulometer, and was 30 ppm. From literature it is known that 1-butyl-3-methylimidazolium tetrafluoroborate should be colorless1. However, the produced ionic liquid had a yellow-orange color, which is due to colored impurities. The chemical nature of the colored impurities in ionic liquids is still not very clear, but it is probably a mixture of traces of compounds originating from the starting materials, oxidation products, and thermal degradation products of the starting materials1. It was impossible to detect the trace amounts of colored impurities by analytical techniques. Decolorization was achieved by silica gel column chromatography separation with


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dichloromethane as the mobile phase (column diameter: 6 cm; column height: 50 cm; thickness of silica layer: 10 cm), where the colored components show less interaction with the mobile phase and remain in the silica layer. 7.3.2 Synthesis of 1-ethyl-3-methylimidazolium chloride The ionic liquid 1-ethyl-3-methylimidazolium chloride ([emim][Cl]) was prepared from 1-methylimidazole and 1-chloroethane (see Figure 7.9), analogous to the production of [bmim][Cl] as described in paragraph 7.3.1.

NN Cl NN+Cl

-

+

Figure 7.9: Preparation of [emim][Cl]

7.3.3 Synthesis of 1-methyl-3-(1H,1H,2H,2H-perfluorooctyl)imidazolium bistriflamide The ionic liquid 1-methyl-3-(1H,1H,2H,2H-perfluorooctyl)imidazolium bistriflamide ([C8F13mim][NTf2]), which is also known as 1-methyl-3-(3,3,4,4,5,5,6,6,7,7,8,8,8-trideca-fluorooctyl)imidazolium bis(trifluoromethylsulfonyl)imide, was prepared by a reaction of 1-methylimidazole and 1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodooctane, followed by metathesis using lithium bis(trifluoromethylsulfonyl)imide (LiNTf2). All starting materials were bought from Sigma-Aldrich with purities over 99.5%. The two-steps preparation is shown in Figure 7.10.

NN (CF2)5CF

3

I NN(CF

2)5CF

3

I-

+

+

NN(CF

2)5CF

3NN

(CF2)5CF

3

I-

+

(CF3SO2)2N-

+ Li(CF3SO2)2N + LiI+

Figure 7.10: Preparation of [C8F13mim][NTf2]

In the first step, 1.70 g (20.7 mmol) of 1-methylimidazole reacts with 9.75 g (20.6 mmol) of 1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodooctane (9.75 g) while heating to 65 oC for 48 hours under nitrogen, yielding 1-methyl-3-(1H,1H,2H,2H-perfluorooctyl)imidazolium iodide ([C8F13mim][I]) as a yellow viscous liquid. This iodide salt is dissolved in 60 ml water and metathized using 6.50 g (22.6 mmol) LiNTf2 in 10 minutes at 60 oC. The formed lithium iodide and the excesses of 1-methylimidazole and LiNTf2 dissolve in water, while the product [C8F13mim][NTf2] forms a separate layer (14.5 g), which was obtained in good yields (>95%).


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7.4 Hydrogenation of methyl (Z)-αααα-acetamidocinnamate In this paragraph, the homogeneously Rh-catalyzed asymmetric hydrogenation of methyl-(Z)-α-acetamidocinnamate (MAAC) in the [bmim][BF4] + CO2 system and subsequent separation of the product N-acetyl-(S)-phenylalanine methyl ester (APAM) is investigated. The reaction, which is related to the most important step in the industrial manufacture of Levodopa, an anti-parkinsonian drug, is shown in Figure 7.11.

NH

O

O

O

NH

O

O

O

+ H2

Rh-catalyst

[bmim][BF4]/CO2

Figure 7.11: Asymmetric hydrogenation of MAAC in the [bmim][BF4] + CO2 system

The reaction is catalyzed by (-)-1,2-bis((2R,5R)-2,5-dimethylphospholano)benzene(cyclo-octadiene)rhodium(I) tetrafluoroborate (Rh-MeDuPHOS), and is depicted in Figure 7.12.

P

P

Rh

BF4-

+

Figure 7.12: Rh-MeDuPHOS catalyst

First, the conditions at which all compounds formed a homogeneous or heterogeneous system were investigated by our group at Delft University of Technology34-36. The homogeneous region was found at room temperature, a pressure of 6.0 MPa and a CO2 concentration of less than 40 mol%. At higher CO2 concentrations, a biphasic system was present. The reaction experiments were carried out in a 160 ml Parr autoclave at room temperature. First, a solution of 20 g/l MAAC and 0.146 g/l Rh-MeDuPHOS catalyst in [bmim][BF4] was prepared under nitrogen in a glove box. Next, 50 ml of this solution was transferred into the autoclave. The autoclave was then closed and the hydrogen and CO2 were added until the desired pressure in the autoclave was reached. During 24 hours the reaction took place in the autoclave under continuous stirring (600 rpm). At the end of the reaction experiment, the remaining pressure was released and the ionic liquid solution was analyzed. Therefore, a sample of the ionic liquid solution was extracted with methyl-tert-butyl ether (MTBE), which dissolves both the reactant MAAC and the product APAM, but is immiscible with the ionic


- 129 -

liquid. The conversion of the extracted sample was determined with gas chromatography (Varian Chrompack CP-1301 GC column) and 1H NMR analysis (Varian Unity, INOVA 300, Varian VXR-400 S). The enantiomeric excesses (ee%) of the samples were determined by chiral high performance liquid chromatography (chiral HPLC) using a Chiralcel OD column with 2-propanol/hexane (10:90) as eluent. The results are shown in Table 7.137. It can be noticed that the reaction rate and selectivity in the homogeneous ionic liquid + CO2 system are comparable to the conventional homogeneous reaction in methanol as solvent38, but higher than in the biphasic ionic liquid + CO2 system39,40. Moreover, the conversion increases and the enantioselectivity decreases with increasing hydrogen pressure (and decreasing CO2 pressure). This was expected, because an increased hydrogen pressure leads to a higher hydrogen concentration in the ionic liquid phase, and thus to higher reaction rates, whereas higher hydrogen concentrations also result in less controlled hydrogenation reactions, and thus to lower selectivities39,40. Finally, it can be concluded that CO2 in low concentrations increases the reaction rate by enhancing the solubility of the reactants (reaching an homogeneous phase), but CO2 in high concentrations decreases the reaction rate because of the dilution effect. Table 7.1: Conversion and enantioselectivity of the asymmetric hydrogenation of MAAC in different solvents and at different pressures, catalyzed by Rh-catalyst at room temperature (reaction time = 24 h)

37-40

Solvent Conversion

(%) ee (%) Substrate/

Rh-ratio

xCO2

(-) p

(MPa) Methanol 100 98 2000 0 1.6 [bmim][BF4] + CO2 (biphasic) 73 93 100 0.75 5.0 [bmim][BF4] + CO2 (single-phase) 100 71 2000 0.17 6.0 [bmim][BF4] + CO2 (single-phase) 95 79 2000 0.33 6.0 [bmim][BF4] + CO2 (single-phase) 91 95 2000 0.40 6.0 The reaction in [bmim][BF4] was repeated for three subsequent cycles to study the recyclability of the Rh-MeDuPHOS catalyst. It was found that the catalyst could be reused without any loss in conversion and enantioselectivity37. Reason is that the ionic liquid stabilizes the catalyst against oxidation6. The subsequent separation was carried out in the biphasic system, which was found at higher CO2 concentrations34-36. For example, when the CO2 concentration was increased to 65 mol% (at 323 K and 12 MPa), an instantaneous demixing into two phases occurred. The light phase consisted of supercritical CO2 with dissolved products (APAM) but did not contain any ionic liquid. The heavy phase consisted of ionic liquid with dissolved catalyst and some remaining product. The process described above is only feasible when the solubility of APAM in supercritical CO2 is sufficiently high. This solubility was measured in the following way: at the bottom of an autoclave a well-defined amount of APAM was placed. CO2 at the desired temperature was pumped into the autoclave until the desired pressure was reached. With a flow meter the amount of entering CO2 was measured. The autoclave with APAM and CO2 was closed and kept at fixed temperature by a heat jacket. The CO2 was stirred in order to enhance mass transport of APAM from the solid phase into the CO2 phase. After waiting until equilibrium


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was reached (30 minutes), the pressure was released and the autoclave was opened. The amount of APAM that was still left in the autoclave was measured. The dissolved amount was calculated from the difference between the initial and final amount of solid APAM in the autoclave41. In Figure 7.13 the solubility of APAM in CO2 at different temperatures (30, 40 and 50 oC) and pressures (8, 10 and 12 MPa) is shown. For convenience, the solubility is shown as function of CO2 density at these conditions36,41.

0.0

0.5

1.0

1.5

2.0

0 200 400 600 800 1000

density of CO2 (kg/m3)

so

lub

ilit

y (

g A

PA

M/k

g C

O2

)

30 C

40 C

50 C

Figure 7.13: Solubility of APAM in CO2

36,41

From Figure 7.13 it can be concluded that the light phase (after instantaneous demixing) contains 1.8 g APAM per kg CO2 (at 323 K and 12 MPa). After separation from the heavy phase, the pressure of the light phase can be decreased to 8 MPa, where solubility is only 0.1 g/kg, indicating that almost all APAM precipitated out of the CO2. In this way, pure product is obtained without any detectable ionic liquid or catalyst, at least below the detection limit of our facilities. APAM was also separated from the ionic liquid by conventional extraction (with CO2 as co-solvent) and by precipitation (with CO2 as anti-solvent) 41. In the extraction process a solution of 10.0 g APAM in 163.5 ml [bmim][BF4] was put into the autoclave. A total amount of 5.595 kg CO2 (measured with a flow meter) was continuously pumped through the autoclave during 30 minutes, while keeping the vessel at a temperature of 323 K and a pressure of 12.0 MPa. After leaving the autoclave, the CO2 entered an expansion vessel in which the pressure was relieved and the product precipitated due to the negligible solubility at ambient pressure. After 30 minutes the pump was turned off and the pressure in the autoclave was relieved. The concentration of APAM in ionic liquid after extraction was measured using High Performance Liquid Chromatography (HPLC) from Waters, type Waters 510 HPLC pump & Waters Symmetry C18-column. The purity of the precipitated APAM was determined using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) from Spectro, type Spectroflame.


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After extraction, the concentration of APAM in [bmim][BF4] was only 1.7 g per 163.5 ml [bmim][BF4]. The amount of dissolved APAM in CO2 is thus 10.0 - 1.7 = 8.3 g in 5.595 kg CO2 (1.48 g/kg, recovery = 83%), which is lower than the solubility in CO2 (1.8 g/kg). This can be due to mass transfer limitations during the real extraction process. The presence of boron in APAM, which indicates the presence of ionic liquid in the product, was determined using ICP-AES. The precipitated APAM contains no detectable [bmim][BF4], indicating that the solubility of ionic liquid in CO2 is lower than 10-5 mole fraction. For the precipitation experiments a solution of 76.3 g APAM in 171.4 ml [bmim][BF4] was put into an autoclave vessel with a filter on the bottom. A total amount of 278 g CO2 (measured with a flow meter), at the desired temperature of 313 K, was pumped into the autoclave until the desired pressure was reached (18.0 MPa). The autoclave was closed and kept at fixed temperature by a heating jacket. The mixture in the autoclave was stirred for 30 minutes. Thereafter, the valve at the bottom of the autoclave was opened and at the same time, more CO2 was pressed into the autoclave to keep the pressure at constant level. In this way the liquid phase was pushed through the filter at the bottom of the autoclave and recovered, but the formed precipitate could not pass through the filter. At the moment that no liquid left the autoclave anymore, the CO2 pump was turned off and the pressure in the autoclave was relieved. The concentration of APAM in the filtrate was measured with HPLC to determine the solubility of APAM in a mixture of [bmim][BF4] + CO2. The crystal form of the precipitated APAM was analyzed using Scanning Electron Microscopy (SEM) from Jeol, type JSM-5400. The concentration of APAM in the filtrate was measured to be 445 g/l (=27.8 g APAM in 171.4 ml [bmim][BF4]). The starting amount of APAM was 76.3 g, indicating that 76.3 – 27.8 = 48.5 g (recovery = 64%) has precipitated. APAM was obtained as crystals in the form of small needles (see Figure 7.14). This is the first time that a product is precipitated from an ionic liquid by using CO2

41.

Figure 7.14: SEM-image of the precipitated APAM (5000x magnified, 10 kV)

41


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7.5 Oxidation of benzylalcohol The second reaction that was tested in an ionic liquid is the oxidation of benzylalcohol with oxygen42, which is shown in Figure 7.15. This reaction is catalyzed by copper(I)chloride with a suitable ligand. The separation of the product benzaldehyde from the ionic liquid by using CO2 was not further studied.

OH O

+ O2 + H2O0.5Cu(I)Cl/ligand

ionic liquid

Figure 7.15: Oxidation of benzylalcohol in an ionic liquid

This reaction has been studied in an ionic liquid before43. In that work, the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) was chosen as solvent, and the 2,2,6,6-tetramethylpiperidinyloxy radical (TEMPO) was chosen as ligand (see Figure 7.16). A conversion of 72% in 24 hours was reached43. Disadvantages of this system are the high sensitivity towards hydrolysis and the low oxygen solubility of [bmim][PF6], and the fact that the TEMPO catalyst is extractable. Here, these disadvantages are addressed by using ionic liquids with a higher hydrolysis stability and a higher oxygen solubility42. Moreover, the catalyst ligand is replaced by a non-volatile and non-extractable one42. The final aim of this work is the development of intrinsically safe and cost friendly oxidation systems by using non-extractable catalysts (easy product recovery) and ionic liquids with a high oxygen solubility (high reaction rate) and no vapor pressure (more safe than other solvents). The approach used is the following:

- The hydrolytically unstable ionic liquid [bmim][PF6] is replaced by the more stable ionic liquid [bmim][BF4]

- The extractable and volatile TEMPO ligand is replaced by the virtually non-extractable and non-volatile polyamine immobilized piperidinyl oxyl (PIPO, oxidation product of Chimassorb 944) ligand (see Figure 7.16)

- The ionic liquid [bmim][BF4] is replaced by the ionic liquid [C8F13mim][NTf2] with a higher oxygen solubility (because of the fluorinated tail)

N

O

N N

N

NH

N (CH2)6

N *

N

O

N

O

* n

Figure 7.16: TEMPO (left) and PIPO (right) catalyst


- 133 -

All three reactions could be carried out without any problems. The results are presented in Table 7.2, and compared to the literature data for the Cu(I)Cl-TEMPO in [bmim][PF6] system, indicating that both ionic liquid and catalyst were successfully replaced. Table 7.2: Conversion data (ncluding substrate/catalyst ratio and time) for the oxidation of benzylalcohol using different catalysts and ionic liquids

System s/c ratio (-) Time (h) Conversion (%)

Cu(I)Cl – TEMPO in [bmim][PF6]43 10 24 72

Cu(I)Cl – TEMPO in [bmim][BF4] 10 24 76 Cu(I)Cl – PIPO in [bmim][BF4] 10 24 83 Cu(I)Cl – PIPO in [C8F13mim][NTf2] 10 24 45 Figure 7.17 shows the conversion as a function of time for the different systems. It can be observed that the PIPO catalyst, which is a polymeric form of TEMPO, performs slightly better than the TEMPO catalyst itself. Thus, the use of PIPO enhances both the catalyst recyclability and activity compared to TEMPO. Moreover, it is noticed that the ionic liquid with the highest oxygen solubility i.e., [C8F13mim][NTf2], results in the highest reaction rate. However, after 5 hours the reaction rate drops. Catalyst poisoning due to impurities in the ionic liquid is expected to be responsible.

Figure 7.17: Conversion versus time for the (i) Cu(I)Cl – TEMPO in [bmim][BF4] system, (ii) Cu(I)Cl – PIPO in [bmim][BF4] system, and (iii) Cu(I)Cl – PIPO in [C8F13mim][BF4] system

In conclusion: the use of the non-volatile PIPO instead of the extractable TEMPO resulted in slightly better yields. The use of an ionic liquid with a higher oxygen solubility seems promising because of the initially high reaction rate.

0

10

20

30

40

50

60

70

80

90

0 5 10 15 20 25 30

time (hour)

co

nvers

ion

(%

)

tempo/BMIMBF4

pipo/BMIMBF4

pipo/C8F13NTf2


- 134 -

7.6 Nucleophilic substitution of 1-methyl-3-phenylpiperazine with 2-chloro-

nicotinonitrile One of the most common reactions in organic synthesis is the nucleophilic substitution reaction. Dipolar aprotic solvents, such as dimethylformamide (DMF) or dimethylsulfoxide (DMSO), are known to accelerate nucleophilic substitution reactions44. However, dipolar aprotic solvents suffer from the disadvantage that they are difficult to remove from the product and that they are noxious and toxic. The use of neutral ionic liquids in nucleophilic substitutions gives similar rate enhancements45,46, but ionic liquids do not suffer from these disadvantages. An example of a nucleophilic substitution reaction is the reaction between 1-methyl-3-phenylpiperazine and 2-chloronicotinitrile, which is a reaction step in the synthesis of Mirtazapine, the active ingredient of the anti-depressant Remeron® with a turnover of over 700 M€ per year47. The products of this reaction step are 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinecarbonitrile and hydrochloric acid. The reaction is shown in Figure 7.18.

N Cl

CN

N

N

CH3

H

N N

CN

NCH

3

+DMF

KF+ HCl

Figure 7.18: Conventional nucleophilic substitution reaction between 1-methyl-3-phenylpiperazine and 2-chloronicotinitrile catalyzed by KF in the solvent DMF

The reaction is conventionally carried out in the solvent DMF and catalyzed by potassium fluoride (KF). Problem is that the DMF is toxic and that the operating conditions (150 oC) are close to the boiling point of DMF (153 oC)47, resulting in significant emissions into the atmosphere. Here, the same reaction is carried out in the ionic liquid [bmim][BF4] as solvent, which could result in a significant improvement in the environmental and safety aspects of this process. It was found that the reactant 1-methyl-3-phenylpiperazine reacts with CO2, so that application of the miscibility windows phenomenon was impossible48. Instead, the reaction was carried out in [bmim][BF4] without addition of any CO2. The model reaction was performed at laboratory scale as follows: In a round/bottom flask, 5.0024 g (0.0361 moles) of 2-chloronicotinitrile, 5.0359 g (0.0286 moles) of 1-methyl-3-phenylpiperazine and 5.1114 g (0.0880) moles of KF were mixed with 30 ml of [bmim][BF4]. The reaction mixture was heated to 150°C for 1.5 hours under nitrogen atmosphere, during which the color of the mixture changed from light yellow to dark red, almost brown. After cooling, 250 ml of saturated NaHCO3 were added in order to neutralize the HCl formed. The aqueous layer was extracted 3 times with a total of 350 ml of ethyl acetate. The collected ethyl acetate layers were washed with water, dried with MgSO4 and evaporated in a rotary


- 135 -

evaporator. Eventually, 7.4076 g (0.0266 moles) of the product 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinecarbonitrile as a dark brown, highly viscous oil was obtained with 84% yield. 1H NMR analysis confirmed the structure of the product. The product crystallized upon standing47. In Table 7.3 the results for the nucleophilic substitution reaction between 1-methyl-3-phenylpiperazine and 2-chloronicotinitrile in the conventional dipolar aprotic solvent DMF and the ionic liquid [bmim][BF4] are presented47. It can be seen that the reaction in [bmim][BF4] occurs at similar rate compared to the reaction in DMF (in both cases a conversion of almost 100% is reached within 1.5 hours). Moreover, the yield of the reaction performed in [bmim][BF4] has been significantly higher than the one obtained in DMF following the same procedure. Therefore, it can be concluded that this nucleophilic substitution reaction has been successfully carried out in an ionic liquid, without the problems associated with conventional dipolar aprotic solvents. Table 7.3: Results for the nucleophilic substitution reaction between 1-methyl-3-phenylpiperazine and 2-chloronicotinitrile in DMF and [bmim][BF4]

Solvent Conversion (%) Yield (%)

DMF >99 73 [bmim][BF4] >99 84


- 136 -

7.7 Hydrolysis of lignocellulosic biomass The last reaction that was tested in an ionic liquid is the hydrolysis of lignocellulosic biomass, followed by separation of its constituents and the subsequent dehydration of xylose into furfural (Figure 7.19). Lignocellulosic biomass mainly consists of cellulose (35 -50%), hemicellulose (20 -35%) and lignin (5-30%). These components are assembled in a complex three-dimensional structure remarkably resistant against chemicals and microbial attack that makes it very difficult to hydrolyze, which is key for its future utilization. An effective dissociation of these components and their separation can lead to the production of several high value products and/or fuels from biomass (the so-called biorefinery)49. Previously, several ionic liquids were found to be able to dissolve lignocellulosic biomass50,51. Most suitable appeared to be the ionic liquid [emim][Cl]. The aim of this work is to use [emim][Cl] as a solvent/reaction medium to dissolve the biomass, to separate the biomass into its constituents, and to convert the hemicellulose part into furfural. It is expected that after hydrolysis the cellulose can be separated from the reaction mixture by precipitation with ethanol, and that the lignin can be separated by precipitation with water. The hemicellulose in the remaining solution can be further converted into furfural.

Figure 7.19: Hydrolysis of lignocellulosic biomass into hemicellulose, cellulose and lignin, followed by subsequent hydrolysis of hemicellulose into xylose, and dehydration of xylose into furfural

First, the dissolution experiments50,51 were repeated using two types of lignocellulosic biomass i.e., (i) the low lignin containing wheat straw, and (ii) the high lignin containing pine wood52. For this, 0.5 g of lignocellulosic biomass and 10 g of [emim][Cl] were weighted into a 50 ml Erlenmeyer with magnetic stirrer (200 rpm). The Erlenmeyer was heated to 125 oC under nitrogen during 5 hours. The acidity (pH) was measured at several time intervals.

hemicellulose

cellulose lignin

hemicellulose lignin cellulose + + H+

H2O

H+ H2O

H+ - 3 H2O

OOH

OH OH

OH

xylose

OO

furfural


- 137 -

Afterwards, the suspension was filtered and visually inspected52. On contrary to literature data, we found that not all biomass was dissolved. Although the solution was transparent after 5 hours, fibers were found on the filter after filtration. In literature, the solution was not filtered, which might explain why complete dissolution was assumed50,51. Moreover, the pH measurements indicated that the solution became more acidic over time. Based on these two observations, it was concluded that lignocellulosic biomass does not dissolve in [emim][Cl], but hydrolyzes in the [emim][Cl], and that the hydrolyzed reaction products (lignin, hemicellulose, cellulose) dissolve in the ionic liquid52. It is expected that the formation of acetic acid (by hydrolysis of the acetate groups in biomass) is responsible for the drop in pH. This reaction is assumed to always occur at temperature above 100 oC, even when completely dry biomass is used, because at these temperatures some water is formed by dehydration52. Because this dehydration process is acid-catalyzed, the total process is autocatalytic. In order to hydrolyze the lignocellulosic biomass completely under mild conditions and to dissolve the hydrolyzed products, we investigated the acid catalyzed hydrolysis of lignocellulosic biomass in [emim][Cl]. So far, sulfuric acid has been used as hydrolysis catalyst in these types of systems53. Here, we choose acetic acid as catalyst52, because this compound is already present in the system. Experiments with 0.5 g of biomass, 10 g of [emim][Cl] and 0, 2, 4, and 6 ml acetic acid were carried out at 100, 125 and 150 oC. The reaction mixture was stirred (200 rpm) for 5 hours under nitrogen. Thereafter, 20 ml ethanol was added in order to precipitate the cellulose. After cooling to room temperature, the suspension was filtered over a 0.22 µm filter. Next, water was added (ratio 1:2 with respect to filtrate) in order to precipitate the lignin, and the suspension was filtered again using a 0.22 µm filter. The precipitates were analyzed by using Scanning Electron Microscopy (SEM) from Jeol, type JSM-5400. The furfural content of the remaining filtrate was analyzed by using High Performance Liquid Chromatrography (HPLC) from Waters, type Waters 510 HPLC pump & Waters Symmetry C18-column52. At 100 oC most of the wood did not dissolve, but the straw partly hydrolyzed and dissolved in the ionic liquid. The residues on the first filter (cellulose precipitation by addition of ethanol) and second filter (lignin precipitation by addition of water) for the straw sample at 100 oC and different amounts of acetic acid added are shown in Figure 7.20. It can be noticed that straw dissolved better with increasing amount of acetic acid (less straw-like fibers on the first filter). Moreover, the amount of lignin precipitated increased with an increasing amount of acetic acid added (increased color on the second filter). At 125 oC the straw dissolved completely, and the precipitate at the first filter (after ethanol addition) had a fiber-like structure from cellulose. Moreover, furfural started to be formed. The results for the furfural production are presented in Table 7.4. The amount of furfural produced increased with increasing acetic acid concentration. The wood did not completely dissolve at 125 oC, because it is more difficult to hydrolyze lignin-rich material in [emim][Cl]. The trend of increasing furfural production with increasing acetic acid concentration was also observed in this case. However, the amount of furfural produced is much lower compared to the results with straw, which is consistent with the lower rate of hydrolysis of wood in the ionic liquid as compared to straw52.


- 138 -

Figure 7.20: Picture of the residues on the first filter (cellulose precipitation by addition of ethanol) and second filter (lignin precipitation by addition of water) for the straw sample at 100

oC and different

amounts of acetic acid added (0, 2, 4 and 6 ml) Table 7.4: Furfural produced as a function of temperature and amount of acetic acid (HAc) added

52

Type of biomass

T (oC) Furfural produced (mass%)

HAc = 0 ml HAc = 2 ml HAc = 4 ml HAc = 6 ml Straw 100 <0.01 <0.01 0.08 0.06 125 <0.01 0.17 0.45 1.40 Wood 100 <0.01 <0.01 <0.01. <0.01 125 <0.01 0.08 0.08 0.29


- 139 -

Figure 7.21 shows the SEM-images of the straw before and after reaction at 125 oC (with 6 ml acetic acid added). It can be seen that the fiber size of the original material is in the order of 500 µm, whereas the size of the fibers of the precipitated cellulose after reaction are in the order of 100 µm.

Figure 7.21: SEM-image of straw before (left) and after treatment with acetic acid (6 ml, 125

oC)

52

It can be concluded that the [emim][Cl] + acetic acid system is a good solvent for the hydrolysis of lignocellulosic biomass into its constituents (cellulose, hemicellulose and lignin), and that these constituents are able to dissolve in [emim][Cl]. Lignocellulosic biomass with a high lignin content is more difficult to hydrolyze. Moreover, the addition of acetic acid as well as an increasing temperature results in both a higher rate of hydrolysis and a higher rate of subsequent dehydration of xylose (formed by hydrolysis of hemicellulose) into furfural.


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7.8 Economic evaluation Because in this chapter several chemical processes (hydrogenation, oxidation, nucleophilic substitution, and hydrolysis) using ionic liquids and CO2 have been described, an economic evaluation is made of one example only. However, it should be realized that the ionic liquid/CO2 technology is applicable to many industrial processes, and that the economical and ecological benefits might also apply in many other cases. Here, an economical evaluation of the asymmetric hydrogenation reaction of MAAC to APAM as described in paragraph 7.4 is made. This reaction is related to the most important step in the production of Levodopa, an anti-Parkisonian drug, which has a market of around 1600 ton per year54. With a price of 2.8 k€ per kg, the annual Levodopa turnover is 4500 M€55. Conventionally, this process is carried out in methanol as solvent. Solvent losses are estimated to be as much as 2.86 kg methanol per kg produced APAM25,54. Moreover, the Rh-MeDuPHOS catalyst deactivates fast (it can only be used during five batches)38-40, indicating that a catalyst make-up of 0.276 g per kg produced APAM is necessary25,54. The last step in the conventional process is the evaporation of the methanol38. At least 14.3 kg methanol has to be evaporated per kg produced APAM25,54. The energy required (∆H) can be calculated from the specific heat (Cp = 2.53 kJ.kg-1.K-1)56 to heat the methanol from room temperature (T0 = 25 oC) to boiling temperature (T = 65 oC)65 and the heat of evaporation (∆vapH = 1099 kJ.kg-1)56 using the following equation57:

( ) HTTCH vapp ∆+−⋅=∆ 0 (Eq. 7.1)

resulting in an amount of 17.2 MJ per kg produced APAM25,54. In the alternative ionic liquid/CO2 process, the amount of catalyst and solvent make-up are much smaller. The catalyst is stabilized by the ionic liquid against oxidation and does not significantly deactivate6. Moreover, the ionic liquid cannot evaporate and lead to emissions into the atmosphere1. Also, the CO2 cannot extract the ionic liquid, because the ionic liquid does not dissolve in the CO2

3,4. A catalyst make-up of once per year and an ionic liquid make-up of once in ten years is assumed, which is equal to 2.3 mg catalyst and 0.0030 kg ionic liquid per kg produced APAM58. Energy is only needed to repressurize the 561 kg of CO2 per kg produced APAM from 80 bar to 120 bar (at 40 oC), which can be estimated using the following equation59 for the compression work, W:

average

pdpW

ρηρη ⋅

∆≈⋅⋅= ∫

11 (Eq. 7.2)

A compressor efficiency, η, of 75% is assumed. The average density of CO2, ρ, in the 80-120 bar range is 628.6 kg/m3 and the pressure difference, ∆p, is 40 bar. Therefore, the amount of energy to pressurize CO2 from 80 bar to 120 bar is 4.8 MJ per kg produced APAM, which is almost four times lower than the amount of energy necessary in the conventional process. Table 7.5 shows the prices of the resources for the conventional process and the alternative ionic liquid/CO2 process for the production of APAM.


- 141 -

Table 7.5: Prices of resources in the conventional and the alternative ionic liquid + CO2 process for the asymmetric hydrogenation of MAAC to APAM


Methanol 0.130 €/kg 60 Rh-MeDuPHOS Catalyst 20 k€/kg 61 Ionic liquid 50 €/kg 1 Electricity 0.019 €/MJ 62 The main differences in variable costs for the conventional process and the ionic liquid/CO2 process for production of 1600 ton APAM per year are presented in Table 7.6. As can be seen from Table 7.6, the variable costs of the ionic liquid/CO2 process are much lower (9.5 M€/year lower) than the variable costs of the conventional process. This difference will become larger in the future, because the energy prices are most likely to increase, while the ionic liquid costs are most likely to decrease due to economies of scale (expanding production). Table 7.6: Main differences in variable costs of the conventional and the ionic liquid/CO2 process for the production of APAM

Amount

per year

Costs

(M€/year)

Methanol (ton) 4600 0.60 Rh-MeDuPHOS catalyst (kg) 440 8.83 Energy consumption (MJ) 27.5

.106 0.52


Total 9.95

Ionic liquid (ton) 4.8 0.24 Rh-MeDuPHOS catalyst (kg) 3.7 0.07 Energy consumption (MJ) 7.68.106 0.15

Ionic liquid/CO2

process

Total 0.46

Table 7.6 does not take into account the differences in fixed costs. The fixed costs of the conventional process include costs for the reactor and the separator(s). Instead, the new ionic liquid/CO2 process can be carried out in one vessel that serves both as reactor and separator, eliminating the need of an additional separation column. However, this vessel should be able to withstand higher pressures, thus requiring a larger wall thickness than ordinary vessels and is therefore more expensive. Even though this may not be more expensive than the additional column needed in the conventional process, the investment still has to be made.


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7.9 Conclusions Ionic liquid/CO2 production processes can be a feasible alternative for the wasteful and energy-intensive conventional production processes. Combining catalysis and separations using ionic liquids and CO2 lead to considerable process intensification when the miscibility windows phenomenon (carbon dioxide-induced ‘single-phase’/’two-phase’ transition) is applied. Using this phenomenon, it is possible to carry out reactions in a homogeneous phase, whereas the separation takes place in the biphasic system, where the products are recovered from the phase that does not contain any ionic liquid. Advantages of this new process set-up are the high reaction and separation rates, the low waste generation and energy consumption, the high product quality and the safe working conditions. Moreover, it can lead to significant economical and environmental benefits. Since the principle of miscibility windows is a general phenomenon, it is likely that the new process set-up is applicable to many industrial processes. The ionic liquid/CO2 technology was (partly) applied to four different types of chemical processes: (i) hydrogenation of methyl-(Z)-α-acetamidocinnamate, (ii) oxidation of benzyl-alcohol, (iii) nucleophilic substitution of 1-methyl-3-phenylpiperazine with 2-chloronicoti-nitrile, and (iv) hydrolysis of lignocellulosic biomass. All reactions could be carried out at high rate and selectivity in the homogeneous ionic liquid phase, in which the reactants and catalysts dissolved. In some cases, CO2 was added in order to increase the reactant solubility. The catalysts could be reused without significant loss in activity or selectivity. The products were easily separated by using the miscibility switch, the addition of CO2 as co-solvent in extractions, and/or the addition of CO2 as anti-solvent (all for the hydrogenation process), or by the addition of ethanol and water as anti-solvent (for the hydrolysis process). The quality of the products recovered from the CO2 phase was high, because it was not contaminated by the ionic liquid or the catalyst. The separation was not further investigated for the oxidation and the nucleophilic substitution processes.


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7.10 References

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22. Gu, Y.; Shi, F.; Deng, Y.; Ionic Liquid as an Efficient Promoting Medium for Fixation

of CO2: Clean Synthesis of α-Methylene Cyclic Carbonates from CO2 and Propargyl Alcohols Catalyzed by Metal Salts under Mild Conditions, J. Org. Chem. 2004, 69

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23. Kim, Y. J.; Varma, R. S.; Tetrahaloindate(III)-Based Ionic Liquids in the Coupling Reaction of Carbon Dioxide and Epoxides to Generate Cyclic Carbonates: H-Bonding and Mechanistic Studies, J. Org. Chem. 2005, 70 (20), 7882-7891.

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Achievement of an Homogeneous Phase in Ternary Ionic Liquid/Carbon Dioxide/Organic Systems, Accepted for publication in Ind. Eng. Chem. Res. 2010.

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methylimidazolium Hexafluorophosphate + CO2 Mixture, J. Chem. Eng. Data 2007, 52 (5), 1638–1640.

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CO2 so Small when Dissolved in a Room Temperature Ionic Liquid? Structure and Dynamics of CO2 Dissolved in [bmim+][PF6

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and the Hydrogenation Catalyst ((R,R)-Me-DuPHOS)Rh(COD)BF4 on the Hydrogen Solubility in the Ionic Liquid 1-Butyl-3-methylimidazolium Tetrafluoroborate, Submitted for publication to J. Supercrit. Fluids 2009.

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System Consisting of Rh-DuPHOS and Ionic Liquid for Asymmetric Hydrogenations, Chem. Commun. 2001, (22), 2314-2315.

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Recovery of Pure Products from Ionic Liquids using Supercritical Carbon Dioxide as a Co-solvent in Extractions or as an Anti-solvent in Precipitations, Green. Chem. 2006, 8 (3), 246-249.

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8 Naturally occurring ionic liquids

By: J. van Spronsen, Y. H. Choi, Y. Dai, R. Verpoorte, G. J. Witkamp, M. C. Kroon and F. Hollmann

___________________________________________________________________________

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8. Naturally occurring ionic liquids

8.1 Introduction In the previous chapter, it was shown that ionic liquids can be environmentally benign and safe replacements for the traditional volatile organic solvents in various chemical processes1. The reason that ionic liquids are considered to be ‘green’ solvents is their negligible vapor pressure2. However, ionic liquids can have a hidden environmental cost because they are synthesized from petrochemical resources1. In a lot of synthesis routes halogen atoms are involved. Halogen materials in ionic liquids are undesirable, because of the low hydrolysis stability, the high toxicity, the low biodegradability and the high disposal cost3,4. For example, fluorinated anions such as PF6

- and BF4- are sensitive to water and may release the corrosive

and toxic hydrogen fluoride1. Moreover, the alkyl halides used in the syntheses of many ionic liquids are greenhouse gases and ozone-depleting materials1. The reason that ionic liquids are also considered to be safe solvents is because their the lack of volatility greatly reduces any chance of exposure other than by direct physical contact with skin or by ingestion1. However, most conventional ionic liquids are irritating and have a toxicity comparable to common organic solvents5. From biological tests it appeared that the toxicity of ionic liquids is mainly determined by the type of cation and that ionic liquids with short alkyl substituents in the cation usually have a lower toxicity5,6. A solution to the problems mentioned above is the development of halogen-free ionic liquids, such as ionic liquids with the alkyl sulfate, the alkyl carbonate and the sulfonate anion3,4. It was also found that some ionic liquids with ester groups in their alkyl side chains are biodegradable4,6,7. However, these ionic liquids are still synthesized using petrochemical resources. Recently, the first ionic liquids from bio-renewable sources were obtained8. These ionic liquids show lower toxicity and higher biodegradability. But it would be most desirable to use naturally occurring ionic liquids, especially as solvents for natural products. So far, it is still unknown whether naturally occurring ionic liquids exist. Plant material does contain the organic cation choline (N,N,N-trimethylethanolammonium, see Figure 8.1)9. This naturally-occurring cation is found in the lipids that make up cell membranes and in the neurotransmitter acetylcholine. This is the only natural cation that is being studied, but so far choline-based ionic liquids are still chemically produced from petrochemical resources. Plant material also contains natural carboxylate anions such as maleate or citrate as metabolites9. Therefore, it might be possible that naturally occurring ionic liquids exist. In the next paragraph, the role of naturally occurring ionic liquids in plant material is discussed, indicating a large likelihood for the existence of naturally occurring ionic liquids.

N+ OH

Figure 8.1: Structure of choline cation

8. Naturally occurring ionic liquids ___________________________________________________________________________

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8.2 Function of natural occurring ionic liquids Plants can produce a huge number of metabolites with a wide range of polarity through complex chemical and enzymatic processing, which enables them to live, grow and reproduce10. It is generally considered that any enzymatic and chemical synthesis should be carried out on the basis of water, a unique natural solvent. However, a vast number of metabolites show poor solubility in water. Especially the plant’s secondary metabolites, which are more diverse and have a more limited distribution compared to primary metabolites like carbohydrates, proteins or lipids, are not at all soluble in water because of the huge variety in their polarity. Although the exact number of metabolites in organisms can not be definitely answered yet, it is estimated that there are more than 3000 different metabolites present in a single plant11. This leads us to the main question: How can plants that produce a vast number of secondary metabolites with a wide range of polarity control all sorts of biosynthetic processing as well as their transportation in spite of their poor water solubility? For example, the Sophora species contains as much as 10-30% of water-insoluble rutin (querceting-3-O-rhamnoglucoside) as dry weight12. This leads to a hypothesis that there might be a natural solvent alternative to water in plants. Many environmental conditions can also lead to water deficit in plants. Periods of little or no rainfall can lead to the meteorological condition of drought. Transient or prolonged drought conditions reduce the amount of water available for plant growth13. However, water deficit can also occur in environments in which water is not limiting. In saline habitats, the presence of high salt concentrations makes it more difficult for plant roots to extract water from the environment. Low temperatures can also result in water stress13,14. For example, exposure to freezing temperatures can lead to cellular dehydration as water leaves the cell and forms ice crystals in intercellular spaces. In the drought condition plants can still survive, which restates the hypothesis for a naturally occurring solvent alternative to water. It is generally accepted that many drought-tolerant plants can regulate their solute potentials to compensate for transient or extended period of water stress, called osmotic adjustment. For the osmotic adjustment, plants use diverse natural ions such as proline, dimethylsulfonio-propionate, glycine betaine, β-alanine betaine, proline betaine and choline-O-sulfate, as well as monomeric sugars such as pinitol and mannitol15-18. Synthesis and accumulation of organic osmolytes is widespread in plants, but the distribution of specific compatible solutes varies among plant species13. In addition, some monomeric sugars e.g., glucose and fructose, can be released from polymeric forms in case of water deficieny19. Once the stress is removed, these monomers can be repolymerized to facilitate rapid and reversible osmotic adjustment. The charged ions and solutes are accumulated in the vacuoles, a cell organelle that can occupy as much as 90% of the volume of a mature plant cell (Figure 8.2). In addition to the role of osmotic adjustment, another function of the solutes can be assumed i.e., the hypothesis that some combination of ions and/or solutes can become a liquid as a natural solvent, alternative to water. In recent years, a new attractive non-aqueous solvent for biocatalysis has emerged, the so-called ionic liquids1. These solvents consist of ions only (no water present), and can have melting points far below the freezing point of water. Moreover, they show high efficiency as reaction media. Using this information it was hypothized that a combination of plant metabolites i.e., naturally occurring ions, acts as water-free natural ionic liquids that are able to dissolve a wide range of water-insoluble metabolites.


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Figure 8.2: Plant cell structure

20

The vacuole is the most plausible cell organelle where the possible naturally occurring water-free solvent can be found, because salts accumulate here in case of water deficiency. In addition to the salt accumulation, there is also a high level of citric acid cycle-related organic acids such as malic acid, citric acid, and fumaric acid as well as sucrose present in the vacuole21. On the basis of this information, a wide range of natural ions is evaluated in the next paragraph in the search for a naturally occurring ionic liquid.


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8.3 Synthesis of natural occurring ionic liquids and deep eutectic solvents Naturally occurring cations and anions (metabolites) were identified and added together in the laboratory, in order to check if they form ionic liquids9. The cation and anion combinations studied are presented in Table 8.1. Table 8.1: Combining naturally occurring cations and anions in order to form ionic liquids or deep eutectic solvents

9

Anion Cation Molar ratio State

Citric acid Choline chloride 1:1 Solid Citric acid Choline chloride 1:2 Liquid Citric acid Choline chloride 1:3 Liquid Malic acid Choline chloride 1:1 Liquid Malic acid Choline chloride 1:2 Liquid Malic acid Choline chloride 1:3 Liquid Fumaric acid Choline chloride 1:1 Solid Fumaric acid Choline chloride 1:2 Solid Fumaric acid Choline chloride 1:3 Solid Maleic acid Choline chloride 1:1 Liquid Maleic acid Choline chloride 1:2 Liquid Maleic acid Choline chloride 1:3 Liquid Malonic acid Choline chloride 1:1 Solid Oxalic acid Choline chloride 1:1 Solid Oxalic acid Choline chloride 1:2 Solid Oxalic acid Choline chloride 1:3 Solid Malic acid Proline 1:1 Solid Malic acid Proline 1:2 Solid Malic acid Proline 1:3 Solid Citric acid Betanine chloride 1:2 Solid Malic acid Betanine chloride 1:1 Solid Maleic acid Betanine chloride 1:1 Solid Proline Betanine chloride 1:1 Solid Arginine Choline chloride 1:1 Solid Glutamine Choline chloride 1:1 Solid Glutamic acid Choline chloride 1:1 Solid Aspartic acid Choline chloride 1:1 Solid Asparagine Choline chloride 1:1 Solid Stearic acid Choline chloride 1:1 Solid Palimitic acid Choline chloride 1:1 Solid Arginine Choline chloride 1:1 Solid Among the ion combinations evaluated in this study, the combinations of choline chloride with malic acid, maleic acid and citric acid result in clear liquids (see Table 8.1). However, only choline citrate is a real ionic liquid. The combination of choline chloride with both malic acid and maleic acid results in the formation of a deep eutectic solvent22. When malic acid (melting point is 130 oC) is combined with choline chloride (melting point is 302 oC), a liquid is obtained at room temperature (293 oC), see Figure 8.3. However, the


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compound choline malate (ionic liquid) is not produced. The reason is that the reaction to choline malate is improbable (under simultaneous production of hydrochloric acid), because the hydrochloric acid is a much stronger acid than malic acid. Instead, a deep eutectic solvent22 (liquid at room temperature 293 oC) was created. This was checked by addition of sodium hydroxide, which results in precipitation of choline malate (this is a solid and not an ionic liquid). The same conclusion was drawn for choline maleate by combining choline chloride with maleic acid, see Figure 8.4.

OH

O

OH

O OH

N+ OH

Cl-

+

Figure 8.3: Deep eutectic mixture of malic acid with choline chloride

OOH

O OH N+ OH

Cl-

+

Figure 8.4: Deep eutectic mixture of maleic acid with choline chloride

Deep eutectic solvents are liquids having a melting point that is much lower than the melting points of the two compounds that form the eutectic mixture. Generally, they are formed between a variety of quaternary ammonium salts and carboxylic acids22-24. The deep eutectic phenomenon was first described in 2003 for a mixture of choline chloride and urea in a 1:2 mole ratio, respectively22. Other deep eutectic solvents of choline chloride are formed with phenol and glycerol23,24. Deep eutectic solvents are able to dissolve many metal salts like lithium chloride and copper(II)oxide25. Also, organic compounds such as benzoic acid and cellulose have great solubility in deep eutectic solvents26. Compared to ordinary solvents, eutectic solvents have a very low volatility and are non-flammable22-24. They share a lot of characteristics with ionic liquids, but they are ionic mixtures and not ionic compounds22. Instead, choline citrate is a real ionic liquid. This compound was formed by dissolving citric acid in water, followed by addition of choline hydroxide (in the ratio 2:1) dissolved in methanol. The solvent (water and methanol) was evaporated. The product choline citrate was a slightly yellow viscous liquid, and not a solid. This is probably the first naturally occurring ionic liquid found, see Figure 8.5.

O

O OH

O

O

O O

N+ OH

Figure 8.5: The ionic liquid choline citrate


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In addition to the ions, sugar-based liquids should be evaluated as deep eutectic solvents. Reason is that monomeric sugars such as glucose and fructose are released by plants against water deficiency, and a large proportion of sucrose produced by photosynthesis is transported into the vacuole during the storage period together with malic acid21. Therefore, glucose, fructose, trehalose and sucrose were added to malic acid, maleic acid and citric acid. The results are presented in Table 8.2. Table 8.2: Combining monomeric sugars with naturally occurring organic acids in order to form deep eutectic solvents

Surprisingly, sucrose and trehalose combined with malic acid and citric acid changed their phase to clean liquids. Thus, naturally occurring deep eutectic solvents can also be created by addition of monomeric sugars to organics acids. Figure 8.6 shows a picture of the solids and liquids studied in this paragraph.

Figure 8.6: Pictures of solids and liquids in this study. From left to right: (1) fructose, (2) glucose, (3) malic acid, (4) choline chloride, (5) malic acid + choline chloride (1:1), and (6) fructose + glucose + malic acid (1:1:1)

In order to check if water-free natural solvents occur in nature, we will try to dissolve metabolites and carry out enzymatic reactions in these solvents (see next paragraphs).

Anion Cation Molar ratio State

Malic acid Glucose (monohydrate) 1:1 Liquid Malic acid Glucose (monodydrate) 2:1 Solid Malic acid Glucose (monohydrate) 4:1 Liquid Malic acid Fructose 2:1 Solid Malic acid Trehalose (dihydrate) 2:1 Liquid Malic acid Sucrose 1:1 Liquid Citric acid Glucose (monohydrate) 2:1 Liquid Citric acid Fructose 4:1 Liquid Citric acid Trehalose (dihydrate) 2:1 Liquid Citric acid Sucrose 1:1 Liquid Maleic acid Glucose (monohydrate) 2:1 Solid Maleic acid Fructose 2:1 Solid Maleic acid Sucrose 1:1 Liquid


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8.4 Dissolution of metabolites in naturally occurring ionic liquids As a next approach to investigate the existence of naturally occurring ionic liquids the solubility of natural products, which are not soluble in water, was evaluated in a few selected natural deep eutectic solvents. Several flavonoids were chosen as the natural water-insoluble products, because they are one of the most abundant water-insoluble plant secondary metabolites. Up to now more than 500 flavonoids have been known27. Most of these flavonoids occur in their glycosides forms (bounded to a sugar molecule) in plants. In spite of large abundance of flavonoids in plants, both the glycoside and the aglycone (non-sugar) part are not soluble in water. Thus, as a model research, the solubility of typical flavonoids including quercetin (aglycone), quercitrin (quercetin-3-O-rhamnoside) and rutin (quercetin-3-O-rhanmoglucoside), which do not show any water solubility, were tested in the naturally occurring deep eutectic solvents28. The structures of these flavonoids are shown in Figure 8.7.

O

OOH

OH

OH

OH

OH

O

OH

OH

OH

O

O

OOH

OH

OH

OH

O

OOH

OH

O

OH

OH

OH

OH

O

OHO

O

OH

OH

OH

Figure 8.7: Structures of quercetin, quercitrin and rutin (left to right)

As shown in Table 8.3 the three flavonoids were found to be well dissolved in the natural deep eutectic solvents, with solubilities that are 2 to 4 orders of magnitude higher as compared to their solubilities in water. Table 8.3: Solubility of flavonoids in several naturally occurring deep eutectic solvents

28

Deep eutectic solvent Solubility (mg/ml)

Quercetin Quercitrin Rutin

Sucrose + Choline chloride 15.63 ± 0.57 12.68 ± 0.38 2.41 ± 0.18 Glucose + Choline chloride 21.56 ± 0.94 7.81 ± 0.20 4.78 ± 0.84 Fructose + Choline chloride 23.34 ± 2.54 11.25 ± 0.64 10.94 ± 1.70 Water 0.300 ± 0.002 0.159 ± 0.001 <0.001 In order to confirm the solubility of flavonoids, the flowers of red rose were extracted in the naturally occurring ionic liquids. The cells of the rose with the red color metabolites are shown in Figure 8.8. It can be observed that the red color metabolites are localized in the epidermis cells. Although the picture does not show the localization of the red color in a single cell in detail, it is expected that the color is found in the vacuoles.


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Figure 8.8: Picture of the cells of flowers of red rose

Extraction with the deep eutectic solvent fructose/glucose/malic acid (1:1:1) resulted in color removal from the flowers into the deep eutectic solvent phase (see Figure 8.9). The structure of the flowers remained intact, with no breakdown of the natural structure. This is again an indication that naturally occurring solvents alternative to water are existent.

Figure 8.9: Picture of red flower extracts in naturally occurring deep eutectic solvents


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8.5 Enzymatic reactions in naturally occurring ionic liquids If ionic liquids and/or deep eutectic solvents are naturally occurring, then it should be possible to carry out enzymatic reactions in these solvents. In that case, one could carry out interesting enzymatic reactions with water-insoluble substrates. An example of such a reaction is the enzymatic oxidation of the water-insoluble linoleic acid, which was investigated in supercritical CO2 in chapter 4. So far, only few reactions have been studied in deep eutectic solvents. These involve the conversion of sugars into 5-hydroxymethylfurfural29-31, a few hydrolase-catalyzed biotransformations32,33 and a laccase-catalyzed coupling reaction34. In this paragraph, the laccase-catalyzed oxidation of ABTS (2,2'-azino-bis(3-ethylbenzthia-zoline-6-sulphonic acid) in several naturally occurring ionic liquids and/or deep eutectic solvents is investigated (see Figure 8.10). As the enzyme system, laccase from Myceliophthora thermophila is used. The ABTS solution is colorless, whereas the product solution is blue, so that conversion is immediately observed.

Figure 8.10: Laccase-catalyzed oxidation of ABTS to its radical cation

Equimolar deep eutectic mixtures consisting of choline chloride, malic acid, glucose and fructose were prepared (see Table 8.4). These deep eutectic mixtures were mixed with a 0.10 M phosphate buffer (pH = 6). In a eppendorf cup 0.90 g of this solution was mixed with 50 mg ABTS solution (1.0 mM) and 50 mg laccase solution (2.0 µM). The overall ratios between the deep eutectic mixture and the water present in the eppendorf cup are also shown in Table 8.4. Table 8.4: Results for the laccase-catalyzed conversion of ABTS in different deep eutectic solvent + water mixtures

Exp. nr. Deep eutectic solvent (mol/mol/mol/mol) Water (w%) Results Chol+Cl- Malic acid Glucose Fructose

0 0 0 0 0 100 ++ 1 1 0 1 1 50 + 2 1 1 0 0 50 - 3 0 1 1 1 50 + + 4 1 1 1 1 50 - 5 0 0 1 1 50 + 6 0 1 1 1 25 +

Table 8.4 presents the results for the laccase-catalyzed conversion of ABTS in several deep eutectic solvents, including the comparison to a blank experiment (in 100% phosphate buffer).


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It can be observed that the reaction does not occur in the two experiments with both acid and chloride present (experiments nr. 2 and 4). However, the reaction is possible with either acid or chloride present. The best results were obtained for the reaction in the 50% fructose + glucose + malic acid (1:1:1) + 50% water mixture (experiment nr. 3). This might be due to the higher acidity, because the oxidation of ABTS is known to be an acid-catalyzed reaction35, even though the acidity of malic acid is very high (pH ~ 2) compared to acid concentration in the blank water-based reaction (pH ~ 6). Finally, it can be noticed that a certain amount of water is required for the reaction to occur. When the amount of water present in the mixture with fructose + glucose + malic acid is decreased to 25% (experiment nr. 6), the reaction rate drops significantly compared to the experiment with 50% water (experiment nr. 3). However, the reaction still occurred at 25% water, indicating that laccase remains active at water concentrations lower than 50% as opposed to literature35. In literature it was suggested that denaturation of the laccase enzyme can occur as a result of a high acidity35. Therefore, it is possible that the laccase deactivates fast in the most successful experiment (experiment nr. 3). In order to test the stability of the enzyme with regard to malic acid, the following experiment was carried out: Laccase was added to a 50% solution of glucose + fructose + malic acid (1:1:1) in water. After waiting for 15 minutes at room temperature the substrate ABTS was added. In this case no reaction occurred, indicating loss of enzyme activity in the first 15 minutes. Addition of fresh enzyme solution resulted in a color reaction giving conclusive evidence that the enzyme was deactivated by the malic acid. In order to circumvent the acidity problem with malic acid, the ionic liquid choline citrate was tested next. This is a real ionic liquid that is not too strong acidic. First the reaction was tested with minor amounts of water added. The ABTS solution was stirred into the choline citrate. Next, the laccase solution was stirred into the ionic liquid. The water content of the resulting viscous oil was about 10%. After an hour no change in color of the reaction mixture was observed indicating that no reaction took place. Thereafter, a layer of phosphate buffer (pH = 6) was carefully put on top of the ionic liquid layer, creating a two phase system (this should be done very carefully in order to prevent mixing of the two phases). Over two hours the two phases remained largely intact. The boundary layer in the upper (buffer) phase slowly became blue. The lower phase did not show any color change. At the end of the experiment the two phases were stirred and ABTS was added resulting in a fast increase in color. From this experiment it can be concluded that the ionic liquid phase containing the substrate and the enzyme slowly dissolves in the upper phase leading to a color reaction. Diffusion of water in the lower (ionic liquid) layer is too slow to lower the concentration to a level at which the enzyme reaction occurs. Finally, it can be concluded that the enzyme is not deactivated by this ionic liquid. These observations support the existence of naturally occurring ionic liquids.


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8.6 Economic evaluation The metabolites used in this chapter to form the deep eutectic solvents and/or ionic liquids (i.e., monosaccharides, naturally occurring acids) are all very cheap in the price range of 1 € per kilo. This compares favorably with the current price of synthetic ionic liquids, which vary from 50-500 € per kilo depending on the scale of production. Moreover, because the metabolites are naturally occurring, there are no environmental, safety or health problems associated with their usage. Why don’t we use natural solvents for natural products? Natural solvents can be used without any health risks in food-grade applications, because they are already part of these natural materials. It will also be easier to obtain licenses for production methods that use natural solvents, with less costs for registration and legislation. Finally, natural solvents can lead to new opportunities. For example, new valuable high-quality natural compounds can be isolated from biomass by using natural solvents. They can also be applied in separation technology, where any cross contamination with aqueous or organic phases does not lead to pollution because they are naturally occurring.


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8.7 Conclusions It is highly probable that naturally occurring ionic liquids exist. They remain liquid in times of water stress, so that the plant can survive periods of drought, saline and freezing conditions. Suggestions for naturally occurring ionic liquids and deep eutectic solvents were made on basis of identification of naturally occurring anions and cations. These natural solvents were able to dissolve several water-insoluble metabolites. Moreover, it was found to be possible to carry out enzymatic reactions in these natural solvents. It can be concluded that natural ionic liquids are a new class of cheap and green solvents with high potential for many processes.


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8.8 References

1. Wasserscheid, P.; Welton, T., Eds. Ionic Liquids in Synthesis; Wiley-VCH Verlag: Weinheim, Germany, 2003.

2. Blanchard, L. A.; Hancu, D.; Beckman, E. J.; Brennecke, J. F.; Green Processing

Using Ionic Liquids and CO2, Nature 1999, 399 (6731), 28-29.

3. Holbrey, J. D.; Reichert, W. M.; Swatloski, R. P.; Broker, G. A.; Pitner, W. R.; Seddon, K. R.; Rogers, R. D.; Efficient, Halide Free Synthesis of New, Lost Cost Ionic Liquids: 1,3-Dialkylimidazolium Salts Containing Methyl- and Ethyl-Sulfate Anions, Green Chem. 2002, 4 (5), 407-413.

4. Garcia, M. T.; Gathergood, N.; Scammells, P. J.; Biodegradable Ionic Liquids. Part II.

Effect of the Anion and Toxicity, Green Chem. 2005, 7 (1), 9-14.

5. Docherty, K. M.; Kulpa, C. F., Jr.; Toxicity and Antimicrobial Activity of Imidazolium and Pyridinium Ionic Liquids, Green Chem. 2005, 7 (4), 185-189.

6. Gathergood, N.; Garcia, M. T.; Scammells, P. J.; Biodegradable Ionic Liquids. Part I.

Concept, Preliminary Targets and Evaluation, Green Chem. 2004, 6 (3), 166-175.

7. Gathergood, N.; Scammells, P. J.; Garcia, M. T.; Biodegradable Ionic Liquids. Part III. The First Readily Biodegradable Ionic Liquids, Green Chem. 2006, 8 (2), 156-160.

8. Handy, S. T.; Okello, M.; Dickenson, G.; Solvents from Bio-renewable Sources: Ionic

Liquids Based on Fructose, Org. Lett. 2003, 5 (14), 2513-2515.

9. Choi, Y. H.; Van Spronsen, J.; Witkamp, G. J.; Verpoorte, R.; Natural Products Extractability in Water-Free Natural Solvents, To be submitted to Nature 2010.

10. Dewick, P. M.; Medicinal Natural Products: A Biosynthetic Approach; John Wiley &

Sons: Chichester, UK, 2002, pp. 2-34.

11. Verpoorte, R.; Choi, Y. H.; Mustafa, R. N.; Kim, H. K.; Metabolomics: Back to Basics, Phytochem. Rev. 2008, 7, 525-537.

12. Shimidzu, M.; Ohta, G.; Solubilization of Flavonoids. VIII. Glucosides in Flos

Sophorae Japonicae, J. Pharm. Soc. Jpn. 1952, 72, 331-333.

13. Buchanan, B. B.; Gruissem, W.; Jones, R. L.; Biochemistry & Molecular Biology of

Plants; American Society of Plant Physiologists: Rockville (MD), USA, 2000, pp. 1162-1163.

14. Hsiao, T. C.; Plant Responses to Water Stress, Ann. Rev. Plant Physiol. 1973, 24, 519-

570.

15. Waldren, R. P.; Teare, I. D.; Free Proline Accumulation in Drought-Stressed Plants under Laboratory Conditions, Plant and Soil 1974, 40, 689-692.


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16. Trossat, C.; Rathinasabapathi, B.; Weretilnyk, E. A.; Shen, T.-L.; Huang, Z.-H.; Gage, D. A.; Hanson, A. D.; Salinity Promotes Accumulation of 3-Dimethylsulfonio-propionate and Its Precursor S-Methylmethionine in Chloroplasts, Plant Physiol. 1998, 116, 165-171.

17. Schwacke, R.; Grallath, S.; Breitkreuz, K. E.; Stransky, E.; Stransky, H.; Frommer, W.

B.; Rentsch, D.; LeProT1, a Transporter for Proline, Glycine Betaine, and -Amino Butyric Acid in Tomato Pollen, The Plant Cell 1999, 11 (3), 377-392.

18. Rhodes, D.; Hanson, A. D.; Quaternary Ammonium and Tertiary Sulfonium

Compounds in Higher Plants, Ann. Rev. Plant Physiol. Plant Mol. Biol. 1993, 44, 357-384.

19. Pettigrew, W. T.; Potassium Deficiency Increases Specific Leaf Weights and Leaf

Glucose Levels in Field-Grown Cotton, Agronomy J. 1999, 91, 962-968.

20. Plant cell structure: http://en.wikipedia.org/wiki/Plant_cell.

21. Philippar, K.; Soll, J.; Intracellular Transport: Solute Transport in Chloroplasts,

Mitochondria, Peroxisomes and Vacuoles, and Between Organelles, In: Yeo, A. R.; Flowers, T. J., Eds. Plant Solute Transport; Blackwell Publishing: New Delhi, India, 2007, pp. 192.

22. Abbott, A. P.; Capper, G.; Davies, D. L.; Rasheed, R. K.; Tambyrajah, V.; Novel

Solvent Properties of Choline Chloride/Urea Mixtures, Chem. Commun. 2003, (1), 70-71.

23. Abbott, A. P.; Boothby, D.; Capper, G.; Davies, D. L.; Rasheed, R. K.; Deep Eutectic

Solvents Formed between Choline Chloride and Carboxylic Acids: Versatile Alternatives to Ionic Liquids, J. Am. Chem. Soc. 2004, 126 (29), 9142–9147.

24. Abbott, A. P.; Capper, G.; Davies, D. L.; Rasheed, R. K.; Ionic Liquids Based upon

Metal Halide/Substituted Quaternary Ammonium Salt Mixtures, Inorg. Chem. 2004, 43 (11), 3447–3452.

25. Abbott, A. P.; Capper, G.; Davies, D. L.; McKenzie, K. T.; Obi, S. U.; Solubility of

Metal Oxides in Deep Eutectic Solvents Based on Choline Chloride, J. Chem. Eng.

Data 2006, 51 (4), 1280–1282.

26. Abbott, A. P.; Cullis, P. M.; Gibson, M. J.; Harris, R. C.; Raven, E.; Extraction of Glycerol from Biodiesel into a Eutectic Based Ionic Liquid, Green Chem. 2007, 9 (8), 868-872.

27. Harborne, J. B.; Williams, C. A.; Flavone and Flavonol Glycosides, In: Harborne, J.

B., Ed. The Flavonoids; Chapman and Hall: London, UK, 1988, pp. 303-328.

28. Dai, Y.; Measurements at Leiden University


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29. Hu, S.; Zhang, Z.; Zhou, Y.; Han, B.; Fan, H.; Li, W.; Song, J.; Xie, Y.; Conversion of Fructose to 5-Hydroxymethylfurfural Using Ionic Liquids Prepared from Renewable Materials, Green Chem. 2008, 10 (12), 1280-1283.

30. Hu, S.; Zhang, Z.; Zhou, Y.; Song, J.; Fan, H.; Han, B.; Direct Conversion of Inulin to

5-Hydroxymethylfurfural in Biorenewable Ionic Liquids, Green Chem. 2009, 11 (6), 873-877.

31. Ilgen, F.; Ott, D.; Kralisch, D.; Reil, C.; Palmberger, A.; König, B.; Conversion of

Carbohydrates into 5-Hydroxymethylfurfural in Highly Concentrated Low Melting Mixtures, Green Chem. 2009, 11 (12), 1948-1954.

32. Gorke, J. T.; Srienc, F.; Kazlauskas, R. J.; Enzymatic Synthesis in Deep Eutectic

Solvents, Proceedings of the 2009 AIChE Annual Meeting, Nashville, USA, 2009.

33. Gorke, J. T.; Srienc, F.; Kazlauskas, R. J.; Hydrolase-Catalyzed Biotransformations in Deep Eutectic Solvents, Chemical Commun. 2008, (10), 1235-1237.

34. Sagui, F.; Chirivì, C.; Fontana, G.; Nicotra, S.; Passarella, D.; Riva, S.; Danieli, B.;

Laccase-Catalyzed Coupling of Catharanthine and Vindoline: An Efficient Approach to the Bisindole Alkaloid Anhydrovinblastine, Tetrahedron 2009, 65 (1), 312–317.

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Solvents for Laccase: Study of Enzyme Activity and Stability, Biotechnol. Bioeng. 2008, 101 (1), 201-207.

9 Conclusions and recommendations

By: J. van Spronsen

___________________________________________________________________________

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9. Conclusions and recommendations The conventionally used volatile organic solvents are based on petroleum. This work shows that these solvents can be replaced by solvents based on renewable sources. Supercritical carbon dioxide is a good replacement for non-polar solvents e.g., hexane, whereas water and (naturally occurring) ionic liquids are good replacements for polar solvents e.g., methanol and dichloromethane. This means that alternative solvents can be used in a wide range of applications. The use of alternative solvents does not only lead to environmental benefits, but also to economical benefits. In many cases, improved performance is reached by using green solvents. The treatment of waste water with eutectic freeze crystallization is a zero waste process using less energy and with soda as valuable new product (chapter 2). The supercritical cotton dyeing process is also a zero waste process using less energy (chapter 3). The supercritical foaming process prevents pentane consumption and emissions (chapter 5). Combining reactions and separations in ionic liquids and supercritical carbon dioxide results in process intensification: lower waste generation, lower energy consumption and smaller equipment (chapter 7). In other cases, the use of the alternative solvents is not yet commercially interesting, but it offers new opportunities for the future. For example, both supercritical carbon dioxide and naturally occurring ionic liquids can be useful solvents for enzymatic reactions (chapter 4 and 8). Moreover, carbon dioxide can be used to extract products from biomass or from naturally occurring ionic liquids (chapter 6 and 8). It is expected that the alternative solvents will be used in larger scale in the future, because the availability of petrochemical resources will decrease dramatically over time, together with an increase in their price. For this reason, increased effort is needed to develop these new solvents in chemical processing within the next decade(s).

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Acknowledgements It all started six years ago after a nice dinner, when Geert-Jan Witkamp asked me if I was interested to help him with some synthetic work at the Laboratory for Process Equipment for a couple of days per week. Because the weather was bad and winter was approaching, I postponed my plans to learn kite surfing and started at API. I have to thank Geert-Jan for this opportunity that turned out to be the most challenging and rewarding task in my career so far. I am also grateful to Rob Verpoorte who gave me the freedom of using his laboratory for the work on natural ionic liquids and for the many inspiring scientific discussions we had together. My special thanks goes out to Maaike Kroon who supervised my PhD project and the writing of this thesis. Although the chapter on eutectic freeze crystallization is a small part of this thesis, I spent half of my time on this subject. With the EFC team we had that special situation where all positions were occupied by strong players that were able to work together. Ad, as the project leader, excelled in project management and it was always a pleasure to be at the meetings because they were short and productive. Hans, as the creative mechanical engineer, was continuously improving the design of our equipment. Geert-Jan was doing the PR and being responsible for the scientific quality of the work. Elif, Marcos, Evelien, Daniela and I were covering the ground work. I also want to thank Gerda for her inspiring contributions in the field of crystallization and management. The work on supercritical dyeing was my first introduction to the field of supercritical carbon dioxide. I would like to thank the people of FeyeCon: Geert, Maaike, Gerard, Frank, Wim, Christof, Martijn, Vanesa, Tjerk, Bas, Rob and PJ for their continuous support and help with the experiments and the equipment. The cooperation with FeyeCon was (and still is) inspiring because it shows how valorization can be achieved. This close cooperation led to a continuous stream of new projects in the field of natural products extraction, extrusion of polymers and enzymatic reactions by using supercritical carbon dioxide. I thank Helene, Jeroen, Kamarza, Albert and Miguel their contributions in these fields. A successful project proposal combining ionic liquids and supercritical carbon dioxide led to a long-lasting cooperation between Geert-Jan, Maaike, Isabel, Cor and myself on basis of friendship. I also thank the co-workers of Cor and Isabel: Bianca, Ali, Eliane, Sona, Frank and Roger for their contributions. The research on natural ionic liquids was developed in close cooperation with Leiden University. I thank the co-workers of Rob, Yuntao and Young, for their contributions. Top quality analyses are an essential part of the investigations. I especially thank Michel for all his time. Research cannot be performed without the help of specialized technicians. I thank Jan, Stefan, Martijn and André for their support with the equipment and the experiments. I thoroughly enjoyed the section meetings, where the students, including Jessica, Somayez, Camiel, Stevia, Michel, Sergio, Sara, Alondra, Luciaan, Kamuran and Martijn, gave their presentations. Also, I like to thank Helma, Rob, Leslie and Ilona for their management support. The financial support from Senter Novem and STW was highly appreciated. Finally, I would like to thank my family Petra, Eric, Laura and Abel. Without their support this work would not have been possible.

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Curriculum Vitae Indentity Name: Jaap van Spronsen Born: March 5th, 1960, Delft, Netherlands Education 1972-1978: VWO, Christelijk Lyceum, Delft 1978-1985: Organic chemistry, Leiden University, Netherlands Work experience Gist Brocades, Delft 1985-1993: Researcher in research & development responsible for the design, scale up and

implementation of new chemical processes related to the synthesis of antibiotics on a multi ton scale. For example, a successful start up of a new 80 M€ production plant with an annual production of 400 ton of antibiotics.

1993-1997: Team leader in production responsible for the design of new chemical processes, troubleshooting and process improvement. Supervisor of the analytical laboratories related to the production facilities. Responsible for Deviation and Failure investigations and other related cGMP issues in the production facility for sterile penicillins.

Delft University of Technology 2003-2005: Researcher at API, faculty 3mE, department Process & Energy. Responsible

for the design of new equipment and new processes related to the use of supercritical CO2. Coaching of students and PhD’s.

Feyecon, Weesp 2005: Researcher Responsible for the design of new equipment and processes related

to the use of supercritical CO2. Delft University of Technology 2005-now: Researcher at API, faculty 3mE, department Process & Energy. Project leader

with a project portfolio containing projects with the aim to design new equipment and new processes with respect to the use of supercritical CO2, eutectic freeze crystallization and ionic liquids. Coaching of PhD’s, students and Post Docs.

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List of publications

Patents

• G. J. Witkamp, J. van Spronsen, M. Hasselaar, Treatment of Molybdate Containing Waste Streams, International Patent WO 2008/115063 A1 (2008).

• M. C. Kroon, A. Shariati, L. J. Florusse, C. J. Peters, J. van Spronsen, G. J. Witkamp,

R. A. Sheldon, K. E. Gutkowski, Process for Carrying Out a Chemical Reaction, International Patent WO 2006/088348 A1 (2006).

• M. V. Fernandez Cid, J. van Spronsen, W. J. T. Veugelers, G. F. Woerlee, Dyeing of

Fibrous Substrate with Reactive Dyestuff in Supercritical or Near Supercritical Carbon Dioxide, International Patent WO 2006/049504 A2 (2006).

Journal articles

• J. van Spronsen, J. P. H. van Luijtelaer, A. Stoop, J. C. Scheper, T. J. de Vries, G. J. Witkamp, M. C. Kroon, Development of a Multiple Hole Die for the Production of Single Large Blocks of Low-Density Polystyrene Using Carbon Dioxide as a Blowing Agent, Submitted for publication to Polym. Eng. Sci. 2009.

• H. Perrotin-Brunel, P. Cabeza Perez, M. J. E. van Roosmalen, J. van Spronsen, G. J.

Witkamp, C. J. Peters, Solubility of ∆9-Tetrahydrocannabinol in Supercritical Carbon Dioxide: Experiments and Modeling, Accepted for publication in J. Supercrit. Fluids 2009.

• J. van Spronsen, M. Rodriguez Pascual, F. E. Genceli, D. O. Trambitas, H. Evers, G.

J. Witkamp, Eutectic Freeze Crystallization from the Ternary Na2CO3-NaHCO3-H2O System: A Novel Scraped Wall Crystallizer for the Recovery of Soda from an Industrial Aqueous Stream, Accepted for publication in Chem. Eng. Res. Design 2009.

• M. Rodriguez Pascual, F. E. Genceli, D. O. Trambitas, H. Evers, J. van Spronsen, G.

J. Witkamp, A Novel Scraped Cooled Wall Crystallizer: Recovery of Sodium Carbonate and Ice from an Industrial Aqueous Solution by Eutectic Freeze Crystallization, Accepted for publication in Chem. Eng. Res. Design 2009.

• M. C. Kroon, V. A. Toussaint, A. Shariati, L. J. Florusse, J. van Spronsen, G. J.

Witkamp, C. J. Peters, Crystallization of an Organic Compound from an Ionic Liquid using Carbon Dioxide as Anti-solvent, Green Chem. 2008, 10, 333-336.

• M. V. Fernandez Cid, K. N. Gerstner, J. van Spronsen, M. van der Kraan, W. J. T.

Veugelers, G. F. Woerlee, G. J. Witkamp, Novel Process to Enhance the Dyeability of Cotton in Supercritical Carbon Dioxide, Textile Res. J. 2007, 77 (1), 38-46.

• M. V. Fernandez Cid, J. van Spronsen, M. van der Kraan, W. J. T. Veugelers, G. F.

Woerlee, G. J. Witkamp, A Significant Approach to Dye Cotton in Supercritical

List of publications ___________________________________________________________________________

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Carbon Dioxide with Fluorotriazine Reactive Dyes, J. Supercrit. Fluids 2007, 40, 477-484.


Woerlee, G. J. Witkamp, Acid-Catalyzed Methanolysis Reaction of Non-Polar Triazinyl Reactive Dyes in Supercritical Carbon Dioxide, J. Supercrit. Fluids 2007, 39

(3), 389-38.

• E. Kühne, C. J. Peters, J. van Spronsen, G. J. Witkamp, Solubility of Carbon Dioxide in Systems with [Bmim][BF4] and Some Selected Organic Compounds of Interest for the Pharmaceutical Industry, Green Chem. 2006, 8, 287-291.

• M. C. Kroon, J. van Spronsen, C. J. Peters, R. A. Sheldon, G. J. Witkamp, Recovery

of Pure Products from Ionic Liquids using Supercritical Carbon Dioxide as a Co-solvent in Extractions or as an Anti-solvent in Precipitations, Green. Chem. 2006, 8, 246-249.


Woerlee, G. J. Witkamp, Excellent Dye Fixation on Cotton Dyed in Supercritical Carbon Dioxide Using Fluorotriazine Reactive Dyes, Green Chem. 2005, 7, 609-616.

• M. C. Kroon, A. Shariati, M. Costantini, J. van Spronsen, G. J. Witkamp, R. A.

Sheldon, C. J. Peters, High-Pressure Phase Behavior of Systems with Ionic Liquids: Part V. The Binary System Carbon Dioxide + 1-Butyl-3-methylimidazolium Tetrafluoroborate, J. Chem. Eng. Data 2005, 50, 173-176.

Conference proceedings

• M. A. Tavares Cardoso, J. van Spronsen, G. J. Witkamp, W. de Jong, J. R. van Ommen, Dissolution and Fractionation of Wood and Straw Using Ionic Liquids, Proceedings of the 2009 AIChE Annual Meeting, Nashville (TN), USA, November 8-13 (2009).

• J. van Spronsen, M. Rodriguez Pascual, F. E. Genceli, H. Evers, G. J. Witkamp,

Process Options for the Recovery of Na2CO3.10aq/NaHCO3 from Aqueous Industrial

Waste Streams by Eutectic Freeze Crystallization, Proceedings of the 17th

International Symposium on Industrial Crystallization (ISIC17), Maastricht, The Netherlands, September 14-17 (2008).

• M. C. Kroon, J. van Spronsen, C. J. Peters, G. J. Witkamp, Crystallization from Ionic

Liquids using Carbon Dioxide as Anti-Solvent, Proceedings of the 17th

International

Symposium on Industrial Crystallization (ISIC17), Maastricht, The Netherlands, September 14-17 (2008).

• M. C. Kroon, V. A. Toussaint, A. Shariati, L. J. Florusse, J. van Spronsen, G. J.

Witkamp, C. J. Peters, Recovery of Organic Compounds from Ionic Liquids by Anti-Solvent Crystallization with Carbon Dioxide, Proceedings of the 2007 AIChE Annual

Meeting, Salt Lake City (UT), USA, November 4-9 (2007).

List of publications ___________________________________________________________________________

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• J. van Spronsen, Dyeing of Natural Fibers in Supercritical Carbon Dioxide, Proceedings of the Netherlands Process Technology Symposium 7 (NPS 7), Veldhoven, The Netherlands, October 29-30 (2007).

• J. van Spronsen, B. Breure, C. J. Peters, I. W. C. E. Arends, G. J. Witkamp, Oxidation

of Benzylalcohol in Ionic Liquids with the Cu(I)Cl/(poly)TEMPO System, Proceedings of the 2006 EUCHEM Conference on Molten Salts and Ionic Liquids, Hammamet, Tunesia, September 16-22 (2006).

• M. C. Kroon, L. J. Florusse, A. Shariati, K. E. Gutkowski, J. van Spronsen, R. A.

Sheldon, G. J. Witkamp, C. J. Peters, A Novel Method of Chemical Processing; Miscibility Windows in Ionic Liquids, Proceedings of the Thermo International 2006

Conference, Boulder (CO), USA, July 30 – August 4 (2006).

• E. Kühne, S. Santarossa, J. van Spronsen, G. J. Witkamp, C. J. Peters, High Pressure Phase Equilibria of a Ternary System of Pharmaceutical Interest: Carbon Dioxide + [Bmim][BF4] +S-Naproxen, Proceedings of the 8th Conference on Supercritical

Fluids and Their Applications, Ischia, Italy, May 28-31 (2006)

• M. C. Kroon, J. van Spronsen, C. J. Peters, R. A. Sheldon, G. J. Witkamp, Recovery of Pure Products from Ionic Liquids using Supercritical Carbon Dioxide as Co-solvent in Extractions or as Anti-solvent in Precipitations, Proceedings of the 8th Conference

on Supercritical Fluids and Their Applications, Ischia, Italy, May 28-31 (2006).

• E. Kühne, J. van Spronsen, G. J. Witkamp, C. J. Peters, Solubility of Carbon Dioxide in Systems with [bmim][BF4] and Some Selected Organic Compounds, Proceedings

of the 1st International Congress on Ionic Liquids (COIL 1), Salzburg, Austria, June 19-22 (2005).

• A. Shariati, M. C. Kroon, V. A. Toussaint, J. van Spronsen, R. A. Sheldon, G. J.

Witkamp, C. J. Peters, Asymmetric Hydrogenation and Catalyst Recycling Using the Ionic Liquid [bmim][BF4] and Supercritical Carbon Dioxide, Proceedings of the 21

st

European Symposium on Applied Thermodynamics (ESAT 2005), Jurata, Poland, June 1-5 (2005).

Reactions and Separations in Green Solvents

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