Thesis Ciclodextrine

Carbohydrate Mediation of Aqueous Polymerizations:Cyclodextrin Mediation of Aqueous Polymerizations of

Methacrylates

Phillip H. Madison, IV

Thesis submitted to the Faculty of the Virginia PolytechnicInstitute and State University in partial fulfillment of the

requirements for the degree of

Mastersin

Chemistry

Timothy E. LongJames E. McGrathThomas C. WardSusan E. Duncan

June 2001Blacksburg, VA

Keywords: cyclodextrin mediation, aqueous free radical polymerization,inclusion complexation, carbohydrate/methacrylic blends


II

Dedication

To my wife, Sarah, who has been there through my time here at VPI &SU and who willbe with me no matter where this journey through life takes us. I am blessed to have such

a good woman by my side.

To Mom, Dad, Ma and Papa for gently pushing me along my entire life to pursuesomething greater.

To Joe and Ann for making me proud to be a big brother.

To all my friends both far and near who have made the effort to stay in touch. You makethe hard times a little easier.

To Mrs. Thomas from Powhatan High and Dr. Simeon Pickard from King College forigniting, fanning, and sharing both the fire for chemistry that most people don’tunderstand, and the ability and desire to share it with those who want to learn.


III

Acknowledgements

I lift up my eyes to the hills-

where does my help com from?

My help comes from the Lord,

the Maker of heaven and earth.

…………………………………Ps 121:1-2

First and foremost I give thanks and praise to God. Through him all things are possible.

I would like to express a wealth of gratitude to my advisor, Dr. Timothy E. Long. Your

imagination is an inspiration, your work ethic and dedication to science are unparalleled,

and the delicate balance that you keep between career and family is most commendable.

Thank you for your patience and guidance throughout my time here.

I would also like to thank my committee members; Dr. James E. McGrath, Dr. Thomas

C. Ward, and Dr. Susan E. Duncan for the knowledge conveyed both in and out of the

classroom environment.

Thanks goes out to the entire Long group as well. Without your companionship and

support this time would have been much more difficult. Special thanks to Jeremy for his

friendship, it is a blessing to have a coworker who shares the same faith: to AJ for the

wealth of knowledge and inherent love of chemistry that you are always willing to share:

and to Dave for fishing and being another example of how chemistry and marriage can be

balanced.

Lastly I would like to thank the other faculty and staff in the chemistry department who

have helped me in the past and who work hard every day to keep this place running

smooth.


IV

Table of Contents

List of Figures..............................................................................................................VI

List of Tables ...............................................................................................................IX

List of Schemes............................................................................................................XI

Abstract ......................................................................................................................... 1

Chapter I: Literature Review ....................................................................................... 31.1 Introduction........................................................................................................ 31.2 Heterogeneous Free Radical Polymerizations ..................................................... 3

1.2.1 General Concepts of Free Radical Polymerization............................................ 31.2.2 Introduction to Heterogeneous Free Radical Polymerizations ......................... 131.2.3 Emulsion Polymerization ............................................................................... 141.2.4 Suspension Polymerization............................................................................. 171.2.5 Dispersion and Precipitation Polymerization .................................................. 19

1.3 Introduction to Cyclodextrins ........................................................................... 201.4 Industrial Applications of Cyclodextrins........................................................... 261.5 Research Interests Involving Cyclodextrins ...................................................... 301.6 Cyclodextrin Mediation of Polymer Synthesis...................................................... 36

Chapter II: Preparation and Characterization of Cyclodextrin/ MethacrylateComplexes.................................................................................................................... 39

Abstract ..................................................................................................................... 392.1 Introduction.......................................................................................................... 402.2 Experimental........................................................................................................ 422.3 Results and Discussion......................................................................................... 432.4 Conclusions.......................................................................................................... 61

Chapter III: Methylated-ββ-Cyclodextrin Mediated Aqueous Polymerization ofHydrophobic Methacrylic Monomers ........................................................................ 63


CHAPTER IV: Emulsion Polymerizations Using Cyclodextrin and Linear Dextrinas Emulsifiers .............................................................................................................. 79

Abstract ..................................................................................................................... 794.1.1 Introduction....................................................................................................... 804.2 Experimental........................................................................................................ 814.3 Results and Discussion......................................................................................... 824.4 Conclusions.......................................................................................................... 88


V

Chapter V: The Preparation and Characterization of Carbohydrate/MethacrylicBlends .......................................................................................................................... 89


CHAPTER VI: Cyclodextrin Mediated Polymerizations in Ethylene Glycol.......... 97Abstract ..................................................................................................................... 976.1 Introduction.......................................................................................................... 986.2 Experimental........................................................................................................ 996.3 Results and Discussion....................................................................................... 1016.4 Conclusions........................................................................................................ 109

Chapter VII: Synthesis of a Novel, Side Chain Liquid Crystalline Monomer andSubsequent Cyclodextrin Mediated Aqueous Polymerization ................................ 111

Abstract ................................................................................................................... 1117.1 Introduction........................................................................................................ 1127.2 Experimental...................................................................................................... 1157.3 Results and Discussion....................................................................................... 1177.4 Conclusions........................................................................................................ 131

CHAPTER VIII: Recommendations For Future Directions.................................. 132


VI

List of FiguresFigure Page

Figure 1.1 General mechanism of free radical polymerization. ........................................ 4

Figure 1.2 Idealized drawing of a typical emulsion polymerization system.................... 15

Figure 1.3 Cyclodextrin size and structure.75 ................................................................. 22

Figure 1.4 Names and structures of typical compounds utilized recently in the formationof host-guest complexes with ββ-CD derivatives.,,,,,,, ................................................. 24

Figure 1.5 Water solubility of ββ-cyclodextrin (ββ-CD), di (DiMe-ββ-CD), and trimethylated(TriMe-ββ-CD) derivatives. ...................................................................................... 31

Figure 2.1 Cyclodextrin size and structure..................................................................... 43

Figure 2.2 CPK models of t-butyl methacrylate and ββ-cyclodextrin in free andcomplexed form...................................................................................................... 45

Figure 2.3. CPK models of cyclohexyl methacrylate and ββ-cyclodextrin in free andcomplexed form...................................................................................................... 45

Figure 2.4 CPK models of 2-ethylhexyl methacrylate and ββ-cyclodextrin in free andcomplexed form...................................................................................................... 45

Figure 2.5 1H NMR of methylated(1.8)-ββ-cyclodextrin in chloroform. ......................... 48

Figure 2.6 1H NMR of 2-ethylhexyl methacrylate in chloroform. .................................. 49

Figure 2.7 1H NMR of 2-ethylhexyl methacrylate (top), MeCD (middle), and thesubsequent complex in chloroform (bottom). .......................................................... 50

Figure 2.8 1H NMR of cyclohexyl methacrylate in chloroform...................................... 51

Figure 2.9 1H NMR of cyclohexyl methacrylate (top), MeCD (middle), and thesubsequent complex in chloroform (bottom). .......................................................... 52

Figure 2.10 1H NMR of n-butyl methacrylate in chloroform.......................................... 53

Figure 2.11 1H NMR of n-butyl methacrylate (top), MeCD (middle), and the subsequentcomplex in chloroform (bottom). ............................................................................ 54

Figure 2.12 1H NMR of t-butyl methacrylate in chloroform. .......................................... 55

Figure 2.13 1H NMR of t-butyl methacrylate (top), MeCD (middle), and the subsequentcomplex in chloroform (bottom). ............................................................................ 56


VII

Figure 2.14 Thermogravimetric analysis comparing a CMA/MeCD complex (0.70mol/1.00 mol) and uncomplexed MeCD. Heating procedure was as follows: (1).Heat from 25 °°C to 120 °°C at 10 °°C/min (2). Hold from 15 min (3). Heat form 120°°C to 250 °°C at 10 °°C/min (4). Hold for 15 min (5). Heat from 250 °°C to 800 °°C at 10/min. ....................................................................................................................... 58

Figure 2.15 TGA of CMA from 25-150 °°C, under N2, at a heating rate of 10 °°C/min..... 58

Figure 2.16 TGA of MeCD from 25-500 °°C, under N2, at a heating rate of 10 °°C/min... 59

Figure 2.17 TGA of CMA/MeCD complex from 25-500 °°C, under N2, at a heating rate of10 °°C/min. .............................................................................................................. 59

Figure 3.1 Thermogravimetric analysis comparing a CMA/ MeCD complex (0.70mol/1.00 mol) and uncomplexed MeCD. Heating procedure was as follows: (1).Heat from 25 °°C to 120 °°C at 10 °°C/min (2). Hold from 15 min (3). Heat form 120°°C to 250 °°C at 10 °°C/min (4). Hold for 15 min (5). Heat from 250 °°C to 800 °°C at 10/min. ....................................................................................................................... 70

Figure 3.2. 1H NMR spectra of CMA, MeCD, CMA/MeCD complex, and poly(CMA)from aqueous polymerization of CMA/MeCD complex. ......................................... 71

Figure 3.3 TEM analysis of precipitate formed from the aqueous polymerization of atBuMA/MeCD complex; performed on precipitated product cast from reactionsolution onto a carbon grid...................................................................................... 76

Figure 3.4 CPK molecular model of a possible tBuMA/ββ-CD complex. ....................... 76

Figure 4.1 Chemical structures of several of the more common ionic emulsifiers, and thestructures of MeCD and linear dextrin..................................................................... 83

Figure 6.1 GPC chromatographs of poly(CMA) that was prepared using the complexbefore (green) and after (red) repricipitaion from THF into 10x vol of water......... 105

Figure 6.2 1H NMR spectrum of poly(CMA) that was prepared using the complex before(top) and after (bottom) reprecipitation from THF into 10x vol of water. .............. 106

Figure 7.1 Names and structures of typical compounds utilized recently in the formationof host-guest complexes with ββ-CD derivatives.,,,,,,, ............................................... 113

Figure 7.1 Chemical structure of methacrylic acid 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl ester. ........................................................................................................... 117

Figure 7.2 1H NMR spectrum of the 4’-hexoxy-biphenyl-4-yloxy hexane byproduct fromthe first step in the liquid crystalline monomer synthesis scheme. ......................... 120

Figure 7.3 1H NMR spectrum of the desired product, 4-hexoxy-4’-biphenol from the firststep in the liquid crystalline monomer synthesis scheme. ...................................... 121


VIII

Figure 7.4 1H NMR spectrum of the desired product, 6-(4’-hexoxy-biphenyl-4-yloxy)-hexanol from the second step in the liquid crystalline monomer synthesis scheme.122

Figure 7.5 1H NMR spectrum of the desired product, 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate from the final step in the liquid crystalline monomer synthesisscheme.................................................................................................................. 125

Figure 7.6 13C NMR spectra of the precursor, 6-(4’-hexoxy-biphenyl-4-yloxy)-hexanol(top) and the desired product, 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate(bottom)................................................................................................................ 126

Figure 7.7 Electron ionized mass spectrum of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexylmethacrylate. ........................................................................................................ 128

Figure 7.8 CPK molecular models of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexylmethacrylate and ββ-cyclodextrin. .......................................................................... 131

Figure 8.1 Example of a cinnimate substituted methacrylic monomer for possiblecyclodextrin mediated aqueous polymerization. .................................................... 134


IX

List of TablesTable Page

Table 1.1 Half-lives (t1/2 = 0.693/kd) of several common free radical thermal initiators atdifferent temperatures in either benzene or toluene. .................................................. 6

Table 1.2 Physical properties of methylated (1.8)-αα, ββ, and γγ-cyclodextrins as reported byWacker Biochem Corporation................................................................................. 25

Table 2.1 Comparison of results from complexation procedures that involved stirring foreither one or six days in chloroform. ....................................................................... 47

Table 3.1 Comparison of results from complexation procedures that involved stirring foreither one or six days in chloroform. ....................................................................... 72

Table 3.2 Polymerizations of t-butyl methacrylate under specified conditions. .............. 74

Table 3.3 Polymerizations of cyclohexyl methacrylate under specified conditions......... 74

Table 3.4 Polymerizations of 2-ethylhexyl methacrylate under specified conditions. ..... 74

Tables 3.5-6 Dependence of Tg on weight % MeCD present in film. Approximately 1mm thick films were optically clear as cast from CHCl3 with up to 20 weight %MeCD..................................................................................................................... 75

Table 4.1 Recipe for emulsion polymerizations using methylated-ββ-cyclodextrin or lineardextrin as surfactants. ............................................................................................. 84

Table 4.2 Results from emulsion type polymerizations incorporating MeCD and lineardextrin in emulsifier concentrations. ....................................................................... 86

Tables 5.3-4 Dependence of Tg on weight % MeCD present in film. Approximately 1mm thick films were optically clear as cast from CHCl3 with up to 20 weight %MeCD..................................................................................................................... 94

Table 6.1 Polymerizations of t-butyl methacrylate under specified conditions. ............ 104

Table 6.2 Polymerizations of n-butyl methacrylate under specified conditions. ........... 104

Table 6.3 Polymerizations of cyclohexyl methacrylate under specified conditions....... 104

Table 6.4 Polymerizations of 2-ethylhexyl methacrylate under specified conditions. ... 104

Table 6.5 Comparison of the results from the polymerizations of the CMA/MeCDcomplex in water and ethylene glycol. .................................................................. 107

Table 6.6 Comparison of the results from the polymerizations of the tBuMA/MeCDcomplex in water and ethylene glycol. .................................................................. 107


X

Table 6.7 Chain transfer constants for methyl methacrylate to various organic solvents.25

............................................................................................................................. 108


XI

List of SchemesScheme Page

Scheme 1.1 Decomposition reaction of persulfate ion in water. ....................................... 7

Scheme 2.1 Preparation of monomer/methylated(1.8)-ββ-cyclodextrin complexes .......... 46

Scheme 4.1 Preparation of the monomer/MeCD complex (Step 1), and subsequentaqueous polymerization (Step 2). ............................................................................ 70

Scheme 5.1 Bulk polymerizations of tBuMA, CMA, and 2EHMA. ............................... 94

Scheme 6.1 Preparation of the monomer/MeCD complex (Step 1), and subsequentpolymerization in ethylene glycol (Step 2). ........................................................... 102

Scheme 7.1 Three step synthesis procedure for the liquid crystalline monomer, 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate................................................... 118

Scheme 7.2 Synthesis scheme for the formation of the side-chain liquid crystallinemethacrylic monomer/cyclodextrin complex, and subsequent aqueouspolymerization...................................................................................................... 129

Phillip H. Madison, IV Abstract 1

Carbohydrate Mediation of Aqueous Polymerizations:Cyclodextrin Mediation of Aqueous Polymerizations of

Methacrylates


Abstract

Cyclodextrin mediation offers a unique mechanism with the potential forinteresting control of reaction parameters. Cyclodextrin mediation of hydrophobicmonomers may offer desirable kinetics over conventional free radical polymerizations,and it has been shown in this work that cyclodextrin mediation facilitates polymerizationof hydrophobic monomers in aqueous solution and in ethylene glycol. It also may be afacile method for controlling relative reactivity of comonomer mixtures.1 In addition,complexation of cyclodextrin with guest molecules has been utilized in selectivesynthesis where the host cyclodextrin has been utilized to sterically hinder the attack ofcertain reactive sites contained within the host cavity. This aspect of inclusioncomplexation could also be utilized in free radical polymerizations of monomers withmultiple reactive double bonds to preferentially reduce the reactivity of the hinderedreactive sites.

This thesis involves the use of methylated (1.8)-β-cyclodextrin (MeCD) as amediator for polymerizations in solvents that would not facilitate polymerization of thepure monomer in the absence of cyclodextrin. This study focuses on the carbohydratemediation of a series of methacrylic monomers. t-Butyl methacrylate, n-butylmethacrylate, cyclohexyl methacrylate, and 2-ethylhexyl methacrylate were complexedwith methylated (1.8)-β-cyclodextrin and subsequently dissolved in either water orethylene glycol. The complexes were studied by 1H and 13C NMR spectroscopy, thinlayer chromatography, CPK modeling, and thermogravimetric analysis, and were foundto have molar ratios of cyclodextrin to monomer as high as 1.0 to 0.72. These complexeswere then free radically polymerized in either water or ethylene glycol and resulted inhigh molecular weight polymers that precipitated out of solution, allowing for facilepolymer isolation through filtration. Isolated yields were found to be as high as 86 %.The majority of the cyclodextrin remained in solution after polymerization. It was alsorecovered and found to be recyclable.

Heterogeneous polymerizations were also performed with 2-ethylhexylmethacrylate in which linear dextrin and methylated (1.8)-β-cyclodextrin were used inemulsifier quantities. It was found that linear dextrin, at concentrations of 3.0 wt%produced a stable latex product with high molecular weight and an isolated yield of 1 Casper, P.; Glockner, P.; Ritter, H. Macromolecules 2000, 33(12), 4361.

Phillip H. Madison, IV Abstract 2

>90%. MeCD on the other hand failed to produce a stable emulsion at concentrationsbetween 0.9-3.0 wt%, but remarkably MeCD at 3.0 wt% gave high molecular weightcoagulated polymer with a yield of >90%. It is proposed that a heterogeneousmechanism inconsistent with the four major types discussed by Arshady2 is taking place.Unlike typical suspension or emulsion polymerizations, the cyclodextrin mediatedpolymerizations are completely homogeneous at the onset, making them more like adispersion or precipitation polymerization. However, in dispersion and precipitationpolymerizations the pure monomer is soluble in the reaction media. In the absence ofcyclodextrin, the monomers utilized in this study possessed no appreciable solubility inthe reaction media. Therefore, it is proposed that cyclodextrin acts as a phase transferagent, effectively solublizing the hydrophobic monomer and allowing for the aqueousdispersion or precipitation type polymerization to occur, depending on the relativesolubility of the components.

Bulk polymerizations of t-butyl methacrylate, cyclohexyl methacrylate, and 2-ethylhexyl methacrylate and their subsequent use in the preparation ofcarbohydrate/poly(alkyl methacrylate) blends was also performed in this project. Bulkpolymers were utilized as references for physical properties for the polymers producedthrough polymerization of the MeCD/monomer complexes in either aqueous solution orin ethylene glycol. 1H NMR analysis of the polymers from both the cyclodextrinmediation and bulk polymerizations indicated that the tacticity of the polymers producedin both cases were identical. The bulk polymers were also used in the preparation ofcarbohydrate/methacrylic blends with potential applications in the areas of selectivebarriers, biodegradable films. Inclusion of drug molecules or antioxidants into thesecyclodextrin containing films also may have potential in drug delivery, or food packagingapplications.

In addition, the side chain liquid crystalline monomer, 6-(4’-hexyloxy-biphenyl-4-yloxy)hexyl methacrylate was synthesized in high purity via a three-step procedure andconfirmed by a combination of mass spectrometry, thin layer chromatography, and 1Hand 13C NMR. This hydrophobic liquid crystalline monomer was subsequentlycomplexed with 1.0-3.0 equivalents of methylated(1.8)-β-cyclodextrin in an attempt toalter the water solubility of the monomer. Complexes of this side-chain liquid crystallinemonomer have not been studied previously and it is proposed that complexation withcyclodextrin will lead not only to novel polymerizations routes for this monomer, but alsoto novel smectic phases for this thermotropic liquid crystalline polymer.

2 Arshady, R. Colloid Polym. Sci. 1992 270(8) 717.

Phillip H. Madison, IV Chapter I: Literature Review 3

Chapter I: Literature Review

1.1 Introduction

This chapter will offer an overview of the literature relevant to this research

project. First it will include a discussion of heterogeneous polymerizations. General

concepts of free radical polymerization will be introduced and some of the more

applicable concepts will be discussed including basic mechanism and rate equations, and

parameters such as kinetic chain length, number-average degree of polymerization and

number average molecular weight. Also, a brief discussion of thermodynamic and

kinetic factors affecting polymerization is included and the roles of sterics, polar forces,

stereoelectronic, bond strengths, and reaction conditions are discussed.

Heterogeneous polymerizations are then discussed. The differences between the

four major types of heterogeneous polymerizations (emulsion, suspension, dispersion,

and precipitation polymerizations) are outlined. Finally, the review will introduce the

structures and chemistry of cyclodextrins. The physical and chemical nature, more recent

industrial applications, and major areas of research are included. In conclusion, the role

of cyclodextrin in polymer synthesis is discussed.

1.2 Heterogeneous Free Radical Polymerizations

1.2.1 General Concepts of Free Radical Polymerization

The concept of free radical chain polymerization was first conceived in the early

1920’s by Staudinger,1 and an accepted mechanism had been established by the 1950’s.2

Presently the mechanism of free radical polymerization is understood to proceed through

three stages; initiation, propagation, and termination.3,4 Figure 1.1 outlines the chemistry

involved in each of these three stages.

1 Staudinger, H. Chem. Ber. 1920, 53, 1073.2 Flory, P. Principles of Polymer Chemistry Cornell University Press, NY 1953.3 Moad, G.; Solomon, D. H. The Chemistry of Free Radical Polymerization Pergamon Press, ElsevierScience, Inc. Tarrytown, NY 1995.


Initiation:

Propagation:

Termination:

combination disproportionation

I2 2 I

I

CH2 C

Y

X

I CH2 C

X

Y

I CH2 C

X

Y

CH2 C

Y

X

n

I CH2 C

X

Y

CH2 C

X

Yn

n

I CH2 C

X

Y

CH2 C

X

Y

+ ICH2C

X

Y

CH2C

X

Ym

I CH2 C

X

Y

CH2 C

X

Y

ICH2C

X

Y

CH2C

X

Yn m

ICH2C

X

Y

CH2HC

X

Ymn

I CH2 C

X

Y

CH C

X

Y

Figure 1.1 General mechanism of free radical polymerization.3

4 Odian, G. Principles of Polymerization John Wiley & Sons, Inc. New York, NY 1991.


Initiation is the first stage and is considered to proceed through two steps. The

first step involves the dissociation of a radical generating species to form an active

radical. This step is considered rate determining for initiation and is dependent on the

rate of dissociation of the initiator, designated by the rate constant kd and the particular

initiator’s efficiency.4 The decomposition of an initiator to form a polymerization

initiating species is generally not a completely efficient process. The radicals produced

are extremely reactive and there are a number of side reactions that can occur, which will

consume some of the radicals produced.5,6,7 For example benzoyl peroxide has been

shown to have an efficiency lower than one due to side reactions such as decarboxylation

of an initiator radical.4 The phenyl radical produced has been shown to either react with

another phenyl radical to yield biphenyl or react with an initiator radical to form a

relatively stable ester product. Therefore, the number of radicals produced by the

decomposition of initiator that actually initiate polymerization is noticeably below the

expected amount if the reaction were to proceed with 100% efficiency. Typically, the

initiating efficiency of most radical generating species is somewhere in the range of 30-

80 %.4

The second step involved in initiation is the reaction of an active radical with

monomer. This reaction is given the rate constant ki. Typical means by which initiating

radicals are formed include thermal, photochemical and redox methods. Among these the

most commonly used initiators are those that are produced by thermal degradation. 2,2’-

Azobisisobutyronitrile (AIBN), benzoyl peroxide, acetyl peroxide, dicumyl peroxide and

dit-butyl peroxide are a few of the more common thermal initiators. In order for an

initiator to be useful its decomposition rate constant (kd) should be in the range of 10-4-

10-6 s-1 under the reaction conditions used.4 The overall rate of initiation is defined based

on the rate determining step involving initiator decomposition and is represented by

equation 1.

RI = fkd[I] (1)

5 Sato, T.; Sato, M.; Seno, M. J. Appl. Polym. Sci. 2000, 75(2), 218.6 Charpentier, P.; DeSimone, J.; Roberts, G. Chem. Eng. Sci. 2000, 55(22), 5341.7 Mahling, F.; Daiss, A.; Kolhapure, N.; Fox, R. Comput.-Aided Chem. Eng. 2000, 8, 427.


where f is the initiator efficiency constant, kd is the rate constant for decomposition of

initiator, and [I] is the concentration of initiator. Typical overall rates for initiation are

approximately 10-6-10-10 mol/L· s.

Table 1.1 Half-lives (t1/2 = 0.693/kd) of several common free radical thermal initiators atdifferent temperatures in either benzene or toluene.4

Half Life atInitiator

50 °C 60 °C 70 °C 85 °C 100 °C 115 °C 130 °C 145 °C

Azobisisobutyronitrile 74 h 4.8 h 7.2 min

Benzoyl peroxide 7.3 h 1.4 h 19.8 min

Acetyl peroxide 158 h 8.1 h 1.1 h

Lauryl peroxide 47.7 h 12.8 h 3.5 h 31 min

t-Butyl peracetate 88 h 12.5 h 1.9 h 18 min

Cumyl peroxide 13 h 1.7 h 16.8 min

t-Butyl peroxide 218 h 34 h 6.4 h 1.38 h

Rate constants are dependent on the temperature at which the reaction is

performed. Table 1.1 shows the temperature ranges in which the rate constants fall

within the acceptable use range for the thermal initiators listed above.4 Aqueous

reactions, however, such as emulsion polymerizations typically utilize water soluble,

redox initiators.8,9,10,11,12,13 Redox initiation involves either the direct electron transfer

between reductant and oxidant or the formation of reductant-oxidant complexed

intermediates known as charge transfer complexes. Scheme 1.1 shows the decomposition

reaction of a typical redox initiation system, the persulfate ion in water. Some redox

initiators can also be useful at lower temperature with the addition of a

coinitiator.12,13,14,15

8 VanderHoff, J. J. Polym. Sci.: Polym. Symp. 1985, 72, 161.9 Cortizo, M.; Scaffardi, L.; Tocho, J; Figini, R. Angew. Makromol. Chem. 1999, 271, 1.10 McCarthy, T.; Williams, R.; Bitay, J.; Zero, K.; Yang, M.; Mares, F. J. Appl. Polym. Sci. 1998, 70(11),2211.11 Shaffie, K.; Moustafa, A.; Mohamed, E.; Badran, A. J. Polym. Sci., Part A: Polym. Chem. 1997, 35(15),3141.12 Shaffei, K.; Ayoub, M.; Ismail, M.; Badran, A. Eur. Polym. J. 1998, 34(3-4), 553.13 Sarac, A.; Prog. Polym. Sci. 24(8) 1999 1149.14 Huang, J.; Zhang, H.; Li, J.; Cheng, S.; Hu, F.; Tan, B. J. Appl. Polym. Sci. 1998, 68(12), 2029.


Scheme 1.1 Decomposition reaction of persulfate ion in water.3

During propagation, the initiated species react with a large number of monomer

molecules to form a long chain species in which one end of the chain is still an active

radical. Typical rate constant values for propagation (kp) are on the order of 102-104

L/mol·s with the overall rate governed by equation 2.

Rp = kp[M· ][M] (2)

where kp is the rate constant of propagation, [M] is the molar concentration of monomer,

and [M· ] is the steady state concentration of active radicals. Typical Rp values are in the

range of 10-5-10-6 mol/L· s.

Polymerization through a double bond involves two possible sites of attack for a

radical species. If the double bond is substituted, or in other words if it is not ethylene,

the carbon that is most highly substituted is referred to as the head position. The least

substituted carbon is known as the tail position. In most cases, the majority of repeat

units (>98-99%) are isoregic or all head-to-tail linkages.4,16 However, under some

circumstances it is possible to increase the number of head to head and tail-to-tail

linkages and make the polymer more aregic. For example, increases in temperature have

been shown to increase the amount of head-to-head placement by a few percent.3,16

Termination occurs when two active radicals come into close enough proximity

that they both react in a way that eliminates the active radicals on both chains. In the

15 Huang, H.; Zhang, H.; Hu, F.; Al, Z.; Tan, B.; Cheng, S.; Li, J. J. Appl. Polym. Sci. 1999, 73(3), 315.

O S O

O

O

O S

O

O

O

H2O O S

O

O

O

O S

O

OH

O

HO


absence of chain transfer, termination is believed to occur by two competing

mechanisms: combination and disproportionation (Figure 1.1). Combination (coupling)

involves the direct reaction of two radical species to form a new C-C single bond

between the two polymeric species. Disproportionation occurs when the radical species

from one chain abstracts a hydrogen atom from the chain end of the second radical

species, resulting in two separate molecules. However, regardless of the type of

termination that occurs the rate of termination is defined by equation 3.

Rt = kt[M· ]2 (3)

where kt is the rate constant for termination and [M· ] is the steady state radical

concentration. Typical rates of termination are of the order of 10-8-10-10, which is close

to rates of initiation (10-6-10-8), but several orders of magnitude lower than the rates of

propagation (10-5-10-6).

In determining the overall rate of polymerization, it is assumed that the

concentration of radicals is constant. This means that the rate of termination is equal to

the rate of initiation. The steady state approximation can then be applied and substitution

can then be made for [M·] to give the overall rate defined by equation 4.

From these rate expressions one can derive the kinetic chain length of a polymer. The

kinetic chain length is defined by the following equation:

ν = (5)

16 Vogl. O.; Qin, M.; Zilkha, A. Prog. Polym. Sci. 2000, 24(10), 1481.

Rp = kp [M]f kd [I]

kt

1/2

(4)

Rp

Rt


Ri

Rp

However, assuming steady state concentration of radicals, kinetic chain length can be

expressed as:

ν = (6)

or in other terms:

ν = (7)

Another important term is the number-average degree of polymerization (Xn). This is

defined as the average number of monomer molecules contained in a polymer molecule.

Xn is dependent on the mode of termination and is given by the expressions:

Xn = ν , for disproportionation (8)

Xn = 2ν , for coupling (9)

Xn is then directly related to the number average molecular weight (Mn) by:

Mn = Xn Mo (10)

where Mo is the molecular weight of the monomer.

Another important factor to consider in free radical polymerization is chain

transfer. In many systems the expected molecular weight, given the extent of termination

expected by either coupling of disproportionation is found to be higher than the observed

molecular weight.4 This phenomenon occurs when the propagating radical reacts with a

compound within the system such as initiator, monomer, solvent, polymer, or additive so

that the radical is transferred and the macromolecule is effectively terminated

prematurely.17,18,19,20 It is therefore obvious that there should be subsequent decrease in

17 Barson, C. in Comprehensive Polymer Science, Vol. 3, Eds. Eastmond, G.; Ledwith, A.; Russo, S.;Sigwalt, P. Pergamon; London, 1989 171.18 Palit, S.; Chatterjee, S.; Mukherjee, A. in Encyclopaedia of Polymer Science and Technology, Vol. 3,Eds. Mark, H.; Gaylord, N.; Boutevin, B. Wiley; New York 1966 575.19 Farina, M. Makromol. Chem., Macromol. Symp. 10/11 1987 255.20 Eastmond, G. in Comprehensive Chemical Kinetics, Vol 14A, Eds. Bamford, C.; Tipper, C. Elsevier;Amsterdam 1976 153.

kp [M]

f kd kt [I] 1/2


the degree of polymerization in the presence of chain transfer of any kind. The actual

effect on Xn is defined by the Mayo equation (11):3

where Xno is the expected number average degree of polymerization in the absence of

chain transfer, CM, CI, CP, and CS are the constants for chain transfer to monomer,

initiator, polymer, and transfer agent respectively and [M], [I], [P], and [T] are the

concentrations of monomer, initiator, polymer, and transfer agent respectively.

The occurrence of chain transfer effectively lowers the molecular weight of a

polymer obtained compared to what would be expected in its absence. This aspect has

been utilized in areas where extremely high molecular weights can be achieved and/or

where high molecular weight polymer is not desirable. For example, chain transfer

agents are added to many industrial emulsion polymerizations in order to obtain

molecular weights low enough that the resulting latex can be directly applied and easily

form a film upon solvent evaporation.21,22,23 The most common chain transfer agents

used historically are the thiols and disulfides,3,24,25,26 and there has been little resent

research dealing with alternative transfer agents.

Free radical chain polymerization is dependent on both thermodynamic and

kinetic factors. A negative change in free energy (∆G) must be observed between

monomer and polymer in order for a polymerization to be thermodynamically feasible.4,27

This applies to a large number of monomeric species, however, thermodynamic

feasibility does not ensure that a polymerization is kinetically feasible under all

21 Plessis, C.; Arzamendi, G.; Leiza, J. R.; Alberdi, J. M.; Schoonbrood, H. A.; Charmot, D.; Asua, J. M. J.Polym. Sci., Part A: Polym. Chem. 2001, 39(7), 1106.22 Puzin, Y.; Egorov, A.E.; Kraikin, V.A. Eur. Polym. J. 2001, 37(6), 1165.23 De la Fuente, J. L.; Lopez, M. E. Macromol. Chem. Phys. 2001, 202(3), 375.24 Plessis, C.; Arzamendi, G.; Leiza, J. R.; Alberdi, J. M.; Schoonbrood, H. A. S.; Charmot, D.; Asua, J. M.J. Polym. Sci., Part A: Polym. Chem. 2001, 39(7), 1106.25 De la Fuente, J. L.; Lopez, M. E. Macromol. Chem. Phys. 2001, 202(3), 375.26 Matsumoto, A.; Tanno, R.; Aota, H.; Ikeda, J. Eur. Polym. J. 2001, 37(5), 1071.27 Billmeyer, F. W. Textbook of Polymer Science John Wiley & Sons, Inc., NY 1984.

Xn o

= 1

Xn

CM CI CP CS[I] [P] [T]

[M][M] [M]+ + ++

1(11)


conditions. The kinetics of a free radical polymerization is of utmost importance.

Though the thermodynamics may be ideal for a multitude of monomers, at times

extremely specific reaction conditions are required to satisfy strict kinetic requirements in

order to obtain high molecular weight polymer. Moad and Solomon3 outline the major

factors to consider when predicting the kinetic feasibility of a polymerization. These

include steric and polar factors, stereoelectronics, relative bond strengths, and reaction

conditions.

Steric influence on kinetics manifests itself in three ways. The first is the amount

of steric hindrance located around the point of attack of the incoming radical to the

monomer. This effect is seen only when there are bulky groups present around the

incoming radical or around the point of attack on the monomer.3,28,29,30,31,32,33,34,35 The

second place where sterics play a role is when there is β-strain induced as the incoming

radical forces a change in hybridization from sp2 to sp3 and forces substituents that were

once planar into a more crowded tetrahedral position.3,36,37 The third steric effect is

found when there is hindrance to adoption of transition state geometry. This strain

usually manifests itself when an intramolecular addition occurs.3

The second major influence on kinetics lies with consideration of polar forces

imposed through substituents. Polar forces are largely responsible for the overall

reactivity and degree of regiospecificity. The electron donating/withdrawing character of

substituents on vinyl monomers will influence both the relative electron density of the

head and tail positions and also the overall electron density of the unsaturation.3 This in

turn affects the overall rate of addition of the attacking radical to monomer as well as the

28 Okamoto, Y.; Yamada, K.; Nakano, T. ACS Symp. Ser. 2000, 768, 57.29 Yin, M.; Baker, G. Macromolecules 1999, 32(23), 7711.30 Somvarsky, J.; Dusek, K.; Smrckova, M. Comput. Theor. Polym. Sci. 1998, 8(1/2), 201.31 Grenier-Loustalot, M.; Da Cunha, L. Eur. Polym. J. 1998, 34(1), 95.32 Kobatake, S.; Yamada, B. Polym. J. 1996, 28(6), 535.33 Penelle, J.; Verraver, S.; Raucq, P.; Marchand-Brynaert, J. Macromol. Chem. Phys. 1995, 196(3), 857.34 Vrhovac, L.; Djurasovic, N.; Velickovic, J. J. Polym. Sci., Part A: Polym. Chem. 1993, 31(1), 45.35 Matsumoto, A.; Oki, Y.; Otsu, T. Macromolecules 1992, 25(12), 3323.36 Matsumoto, A.; Hirai, F.; Sumiyama, Y.; Aota, H.; Takayama, Y.; Kameyama, A.; Nakanishi, T. Eur.Polym. J. 1999, 35(2), 195.37 Azuma, H.; Katagiri, Y.; Yamabe, S. J. Polym. Sci., Part A: Polym. Chem. 1996, 34(8), 1407.


relative reactivity of the head and tail of the monomer with respect to the incoming

radical. Thus, this will in turn influence the point of attack for the incoming radical. For

example vinyl fluorine monomers have been reported to result in approximately 12 %

head-head linkage3,16 where as typical percentages of head-head linkages for most

polymers is only approximately 2-3 %.4 A fluorine substituent is electron withdrawing

and will pull electron density away from the double bond. This will make the double

bond more reactive to electrophilic radicals such as halogenated methyl radicals (i.e.

Cl3C· , or F3C· ), but will also change the relative electron density of the head and tail

positions. A halogen substituent will pull electron density from both the head and tail

positions, but not to the same extent. The head position will feel the effect more than the

tail position. This will cause the head position to have less electron density than the tail

when the substituent is electron withdrawing. If the substituent is electron donating, then

the opposite effect is observed. The double bond will have increased overall reactivity

toward nucleophilic radicals (i.e. Me· ) and the head position will have more electron

density than the tail.

Moad and Solomon3 also discussed the stereo electronic requirements and the

effect of reaction conditions on radical reactions. Stereoelectronics come into play when

considering that the incoming radical must attack perpendicular to the plane of the

unsaturated portion of the molecule. Intramolecular interactions have been found to

inhibit such alignment in cases, giving a product that is less thermodynamically stable.

Reaction conditions such as temperature and solvent have also been found to greatly

impact regiospecificity and rates of polymerization. These factors discussed collectively

determine the regioselectivity, or the relative head vs. tail addition of a radical to

monomer.

One of the major disadvantages of free radical polymerization when compared to

other chain polymerizations such as the anionic or cationic types is that there is certain

level of control that cannot be achieved, which leads to a broader distribution of

molecular weights. In recent years there have been advances in the area of free radical

polymerization that allow for a more controllable polymerization. One method,


discovered by Georges and coworkers38 in 1993 involves the addition of a stable free

radical species. The presence of these stable free radical compounds have been found to

allow for greater control of polymerization leading to molecular weight distributions

approaching values obtainable through anionic polymerizations.39,40,41 This is believed

to be the result of the stable nitroxide radical species reacting with the propagating

radical to form a chemical bond that essentially caps the polymeric radical. However,

this chemical bond is labile at high temperature (> 100 °C) and equilibrium is established

between the free and capped forms of the polymeric radical. This equilibrium leads to

product with a narrower molecular weight distribution.

The presence of a stable nitroxide capped radical at low temperatures also allows

for the formation of block polymers. The nitroxide containing polymer products can be

isolated and then subsequently raised to an appropriate reaction temperature where chain

addition of a second monomer could occur. In this way multilblock42,43 and star44

copolymers have been synthesized via free radical chain polymerization.

1.2.2 Introduction to Heterogeneous Free Radical Polymerizations

A heterogeneous polymerization is a polymerization in which there are at least

two distinct phases at some point during the reaction.4 In aqueous heterogeneous

polymerizations, water is the continuous phase and the monomer and/or the final polymer

is the dispersed phase. The initiator used can be soluble in either of the two phases, and

additives can be used in order to stabilize different size particles. The particles formed

can be nearly anything from regularly dispersed spheres on the order of 50 nm to an

irregularly shaped precipitant on the order of a few mm. The following sections will

attempt to define each of the four types of heterogeneous polymerizations of concern

including emulsion, suspension, dispersion and precipitation. Each of the techniques will

38 Georges, M.; Veregin, R.; Peter, M.; Hamer, G. Macromolecules 1993, 26(11), 2987.39 Kazmaier, P.; Moffat, K.; Georges, M.; Veregin, R.; Hamer, G. Macromolecules 1995, 28(6), 1841.40 Hawker, C. Acc. Chem. Res 1997, 30, 373.41 Malmstrom, E.; Hawker, C. Macromol. Chem. Phys.1998, 199, 923.42 Zou, Y.; Jian, L.; Zhuang, R.; Ye, J.; Dai, L.; Zheng, L. Macromolecules 2000, 33(13), 4745.43 Hawker, C. J.; Hendrick, J. L.; Malmstrom, E.; Trollsas, M.; Stehling, U. M.; Waymouth, R. M. ACSSymp. Ser. 1998, 713, 127.


be defined according to the four criteria outlined by Arshady45 and others4,27,46 with

explanations as to where common overlap may take place. The four criteria include

initial state of the polymerization mixture, the kinetics of polymerization, the prevalent

particle forming mechanism, and the state, shape and size of the resulting polymer

particles.

Specifically defining a heterogeneous polymerization is not an easy task. Over

the years there have been distinctions that are proposed to differentiate them in terms of

initial and final states of reactants, kinetics, and sizes of particles formed. However, at

times there is no clear line defining each type since a simple modification of one may

cause it to slip into the realm that defines another. The following sections represent the

most recent compilation of defining attributes for each of the heterogeneous aqueous

polymerizations with distinctions being made primarily based on those established by

Arshady45 and a number of general texts2,3,4,27,46 outlining the different techniques.

1.2.3 Emulsion Polymerization

The initial state of an emulsion polymerization consists of an insoluble monomer

dispersed in water by aid of a surfactant, or surface-active agent, and the initiator solvated

by the continuous phase. This discussion will deal with an aqueous, continuous phase.

Above a certain concentration some of the surfactant molecules are able to aggregate

together to form small micelles on the order of 2-10 nm. The concentration above which

micelles are formed is known as the critical micelle concentration (CMC).45 At the onset

of polymerization, monomer is present mostly (>95%) in the form of monomer droplets

whose size is generally dependent on the rate of stirring. However, a small amount is

dissolved in the water and can be absorbed by the surfactant micelles.

Figure 1.2 depicts a typical emulsion polymerizations system. Since the initiator

is water-soluble, a monomer is initiated in the aqueous, continuous phase and either

quickly absorbed into a monomer-swollen micelle where propagation occurs or

44 Pasquale, A. J.; Long, T. E. J. Polym. Sci., Part A.: Polym. Chem. 2000, 39(1), 216.45 Arshady, R. Colloid Polym. Sci. 1992, 270(8), 717.46 Painter, P.; Coleman, M. Fundamentals of Polymer Science Technomic Publishing Co., Inc. Lancaster,PN 1997.


undergoes a higher degree of solution type polymerization. In the second case, the

oligomeric radicals become insoluble and precipitate through homogeneous coagulation

onto themselves where they are then stabilized by absorbing surfactant and monomer

from solution. These two particle-forming mechanisms are known as heterogeneous

(micellar) and homogeneous nucleation respectively and are thought to be competing

mechanisms.

Figure 1.2 Idealized drawing of a typical emulsion polymerization system.4


Polymerization continues in the monomer-swollen micelles. Monomer supplied

from the monomer droplets in the aqueous phase is continuously absorbed by the

micelles to feed the propagating chain. The dissolved monomer is subsequently

replenished in the aqueous phase from the monomer droplets. In this way, the micelles

grow while the monomer droplet size decreases. One should note that there are several

orders of magnitude difference between the diameters of the monomer droplets (1-10

µm) and the micelles (2-10 nm). In addition, the total number of monomer droplets and

micelles are typically 1010-1011 mL-1 and 1017-1018 mL-1 respectively. This indicates that

the total surface area of the micelles is several orders of magnitude higher than that of the

droplets. This aspect is of importance because it explains why polymerization takes place

exclusively in the micelles and virtually no polymerization (<1 %) takes place in the

monomer droplets. This substantially larger surface area translates into radical

absorption and polymerization occurring exclusively in the surfactant micelles.

The rate of polymerization is a complicated expression that varies with a number

of different parameters including initiator concentration, temperature, surfactant

concentration, monomer concentration, and extent of reaction.45,47,48,49,50,51 In general,

emulsion polymerizations are known to simultaneously achieve high degrees of

polymerization and high rates. This is one of the major advantages of this type of

polymerization. Each micelle is considered to contain either one or zero active radicals at

any given time. The rate of radical absorption is considered to be fairly small and the

rates of propagation are high given that monomer concentrations in the micelles can be as

high as 5 M. The rate of termination is also small because it is limited by the rate at

which another radical is absorbed by an active micelle. When a radical enters an active

micelle, termination takes place instantaneously for all practical purposes and the micelle

is dormant until another radical enters.

47 Gilbert, R. Emulsion Polymerization: A Mechanistic Approach Academic Press, 1995.48 Feeney, P.; Napper, D.; Gilbert, R. Macromolecules 1984, 17(12), 2520.49 Vanderhoff, J. J. Polym. Sci.: Polym. Symp. 1985, 72, 161.50 Gol’dfein, M.; Kozhevnikov, N.; Trubnikov, A. Polym. Yearb. 1985, 12, 89.51 Poehlein, G. ACS Symp. Ser. 1985, 285, 131.


Emulsion polymerizations are thought to occur in three distinct stages, and the

rates of polymerization depend on the stage.4,47,48,49,50,51 In stage one, the overall rate is

increasing as micelles are gradually absorbing active radicals, which begin chain

propagation. Stage two begins when the concentration of active micelles reaches

equilibrium. During this stage the micelles are growing as more monomer is absorbed

from the aqueous phase to replace that consumed by propagation radical chains, and the

size of the monomer droplets are decreasing as monomer is extracted from them to

replace that absorbed from the aqueous phase. The rate of polymerization is usually

constant during stage two. When all the monomer is depleted from the monomer

droplets, a steady decline in rate is observed due to a steady decrease in monomer

concentration within the micelles. This is referred to as stage three. The final product of

an emulsion polymerization is a latex. The resulting polymer is stabilized in the form of

evenly dispersed spheres (50-300 nm) by adsorption of surfactant.45

1.2.4 Suspension Polymerization

The major difference between an emulsion and suspension technique is that in a

suspension polymerization both the monomer and initiators are insoluble in the

dispersant.45 Also, a stabilizer is utilized rather than an emulsifier. The locus of

polymerization in a suspension takes place within the stabilized monomer droplets since

the initiator is monomer soluble. Given that a stabilizer is used rather than an emulsifier

continuous stirring is required to maintain a stable suspension.4,52,53,54,55,56 In emulsion

polymerizations, it is typical for the emulsifier and other additives to constitute up to 5 %

of the final polymeric product. These absorbed impurities can be extremely difficult to

remove and in most cases are left in the product. For many applications, the presence of

such impurities is undesirable. For applications where polymer in the form of solid beads

is applicable, suspension polymerization may be an attractive alternative method.

52 Yuan, H.; Kalfas, G.; Ray, W. J. Matr. Sci., Rev. Macromol. Chem. Phys. 1991, C31(2-3), 215.53 Warson, H. Polym., Paint, Colour J. 1983, 173(4101), 541.54 Warson, H. Polym., Paint, Colour J. 1988, 178(4226), 865.55 Warson, H. Polym., Paint, Colour J. 1988, 178(4220), 625.56 Brooks, B. Makromol. Chem., Macromol. Symp. 1990, 35-36, 121.


One of the advantages of suspension polymerization over typical bulk

polymerizations are that it offers the kinetics of a bulk polymerization, but the

temperature is easily controlled through manipulation of the dispersant, which is water in

most cases. Also, it has a lower viscosity when compared to bulk polymerization so

stirring is easier, and the product is in the form of spherical beads. Solution

polymerization has the advantages of allowing for facile control of temperature and low

viscosity also, however the kinetics and yields obtained in solution vary depending on

solvent and concentration, and in many cases are lower than those obtained through

typical heterogeneous polymerizations. In addition, the introduction of a solvent may

also require considerations of other factors such as chain transfer to solvent.

A suspension polymerization can be considered to be many small water-cooled

bulk reactions, and kinetics are consistent with this model. Ray and coworkers52 outline

two distinct types of suspension polymerizations. The first of these is termed the “bead

suspension polymerization” and the second is known as a “powder suspension

polymerization”. These two types of suspensions vary in terms of solubility of resulting

polymer in its monomer. Styrene and vinyl chloride are typical examples of monomers

that undergo bead and powder suspensions respectively. In a bead suspension, the

polymer is soluble in the monomer making the dispersed droplets homogeneous

throughout the process. However in the case of a powder suspension the polymer is

insoluble in its monomer and thus precipitates to give a heterogeneous droplet system.

The stabilizer is a crucial component of the suspension mixture.4,45,52,53,54,55,56

There are generally two types of suspending agents used today. The first type consists of

water-soluble organic polymers. This type of stabilizer acts in two ways. It promotes

dispersion by decreasing the interfacial tension between monomer and dispersed phase

and also creates a thin layer surrounding the droplet, which prevents coalescence during

droplet collisions. The second type of stabilizers is composed of inorganic powders. The

mechanism of adsorption of these compounds is not all together understood, however,

compounds such as NiO, CaCO3, CaO, Al2O3, and Al(OH)3 are common inorganic

powders that are utilized as stabilizers in industrial scale suspension polymerizations.


Inorganic powders are generally chosen as stabilizers over organic polymer systems

because they are easily removed, generally cheaper, able to reduce the deposit of particles

on reactor walls, and generally more environmentally benign.

The particles formed from suspension polymerization are on the order of 20 µm–

20 mm. Arshady45 reports that attempts to achieve particle sizes smaller than this by

suspension polymerization techniques results in competing emulsion polymerization,

which is undesirable. The resulting size of the polymer particle has been found to

roughly equal the size of the initial dispersed monomer droplets. Many factors influence

the size of the particles including concentration of stabilizer, relative ratios of dispersant

and dispersed phase, viscosities of the two phases, and stirring speed. Warson53,54,55 has

also reported that alterations in the stirring mechanism (i.e. blade type and width, and

reactor volume) can also have a dramatic effect on both the particle size and temperature

control.

1.2.5 Dispersion and Precipitation Polymerization

The major difference between dispersion and precipitation polymerizations and

emulsion or suspension techniques is that dispersion and precipitation polymerizations

are homogeneous at the onset of reaction.45 Both the monomer and initiator are soluble

in the reaction media while the resulting polymer is insoluble. The major difference

between dispersion polymerization and precipitation polymerization is the degree of

solubility of the polymer in the reaction media. In the dispersion mechanism, the

growing polymer is swelled by the media,57,58,59,60,61 while in a precipitation

polymerization the polymer truly precipitates and is not swollen by the solvent.62,63,64,65,66

57 Saenz, J.; Asua, J. J. Polym. Sci., Part A: Polym. Chem. 1995, 33, 1511.58 Shen, S.; Sudol, E.; El-Aasser, M. J. Polym. Sci., Part A: Polym. Chem. 1994, 32, 1087.59 Barrett, K. (ed) Dispersion Polymerization in Organic Media John Wiley & Sons; London; 1975.60 Kumar, D.; Butler, G. J. Mater. Sci., Rev. Macromol. Chem. Phys. 1997, C37(2), 303.61 Slomkowski, S.; Gadzinowski, M.; Sosnowski, S. Macromol. Symp. 1998, 132, 451.62 Li, W.; Stover, H. J. Polym. Sci., Part A: Polym. Chem. 1999, 37, 2899.63 Li, W.; Stover, H. J. Polym. Sci., Part A: Polym. Chem. 1999, 37, 2295.


In dispersion polymerization the components start out homogeneous. Initiation

occurs in the media and polymer chains begin to grow. Depending on the solvency of the

media, the polymer particles then phase separate forming primary particles. These

particles are then swollen with monomer and solvent and thus the polymerization then

proceeds mainly within these particles. As a result the particles take on a spherical shape

and result in a particle size on the order of 0.1-10 µm.45 The particles can be made more

uniform by the addition of a steric stabilizer.

Precipitation polymerization initially proceeds in a similar manor as dispersion

polymerization. As with dispersion polymerization, the components start out

homogeneous and initiation occurs in the media. Polymerization also takes place largely

in the media, however, this leads to continuous nucleation and coagulation of the polymer

into irregularly shaped particles as they precipitate. Further polymerization does not take

place in the precipitated particle and though addition of stabilizers may result in more

uniform particles they are still irregularly shaped due to the method of formation.45

1.3 Introduction to Cyclodextrins

Cyclodextrins (CD) have been described as “seductive molecules, appealing to

investigators in both pure research and applied technologies”.67 Judging by the

logarithmic growth in publications and patents68 dealing with these compounds since

their discovery this description is not undeserved. CDs are cyclic molecules composed of

glucopyranose ring units to form truncated cone type, doughnut structures.69 The most

common are the α, β, and γ-cyclodextrins which are composed of six, seven, and eight

sugar units respectively. The exterior of the CDs are hydrophilic while the interior is

hydrophobic, and the different CDs possess different cavity sizes according to the

number of glucopyranose rings present (Figure 1.3).

64 Downey, J.; Frank, R.; Li, W.; Stover, H. Macromolecules 1999, 32(9), 2838.65 Bunyakan, C.; Hunkeler, D. Polymer 1999, 40, 6213.66 Bunyakan, C.; Hunkeler, D. Polymer 1999, 40, 6225.67 D’Souza, V.; Lipkowitz, K. Chem. Rev. 1998, 95(5), 1741.68 Szejtli, J. Chem Rev. 1998, 98(5), 1743.


CDs were first noted in an 1891 publication as simply a crystalline substance

obtained from digestion of starch. Villiers70 referred to the substance as cellulosine.

Twelve years later, Schardinger71 observed the same substance and was able to isolate

and examine it. Schardinger was the first to extensively examine CDs in the late 1800s

and for this reason CDs are often referred to as Schardinger dextrins. It wasn’t, however,

until the 1930s that Freudenberg established the true structure of CDs, with assistance

from the observations made by Karrer and Miekeley.68 In the 1950s, the chemical

process for the production of CDs was thoroughly examined by French and coworkers,72

and the existence of even larger CDs was confirmed. Also, during this time Cramer and

coworkers first began to uncover CDs potential as complexation agents.68 They

examined the ability of CDs to complex with a variety of drug molecules, and noted the

stabilization, volatility reduction, and solubility changes that occurred as a result of

complexation. They subsequently obtained a patent73 in 1953 that encompassed the

potential drug related applications foreseen as a result of their studies.

69 Bender, M.; Komiyama, M. Cyclodextrin Chemistry Springer Verlag,, NY 1978.70 Villiers, A. Compt. Rend. 1981, 112, 536.71 Schardinger, F. Unters Nahr u. Genussm 1903, 6, 865.72 French, D. Adv. Carbohydr. Chem. 1957, 12, 189.73 Freudenberg, K.; Cramer, F.; Plieninger H. Ger. Patent 895-769, 1953.


Figure 1.3 Cyclodextrin size and structure.75

Since that time the number of patents and papers have increased exponentially.68

In 1981 the first international symposium74 was organized where lecturers would have the

opportunity to summarize their most recent results. Since then,

symposia74,75,76,77,78,79,80,81,82 have been held every second year and presentations have

increased in both quantity and quality. Today, CD is a relatively inexpensive material

and an important industrial commodity in many ways.

74 Szejtli, J., Ed.; Proc.1st Int. Symp. on Cyclodextrins, Budapest, 1981; D. Reidel Publ.: Dordrecht, 1982.75 Atwood, J. L., Davies, J. E. D., Osa, T., Eds. Clathrate Compounds, Molecular Inclusion Phenomena andCyclodextrins; Proc. of Third Int. Symp. on Clathrate Compounds and Molecular Inclusion and the SecondInt. Symp. on Cyclodextrins; Tokyo, 1981, D. Reidel Publ. Co.: Dordrecht, 1985.76 Atwood, J. L., Davies, E. D., Eds. Inclusion Phenomena in Inorganic, Organic and Organometallic Hosts,Proc. Third Int. Symp. on Inclusion Phenomena and the Third Int. Sympt. on Cyclodextrins; Lancaster,1986; D. Reidel Publ: Dordrecht, 1987; p 455.77 Huber, O., Szejtli, J., Eds. Proc. Fourth Int. Symp. on Cyclodextrins, Munich, 1988; Kluwer AcademicPubl.: Dordrecht, 1988.78 Duchene, D., Ed. Minutes of the Fifth Int. Symp. on Cyclodextrins, Paris, 1990; Editions de Santé: Paris,1990.79 Hedges, A. R., Ed. Minutes of the Sixth Int. Symp. on Cyclodextrins, Chicago, 1992; Editions de Santé:Paris, 1992.80 Osa, T., Ed. Proceedings of the Seventh International Cyclodextrin Symposium, Tokyo, 1994; Publ.Office of Business Center for Academic Societies of Japan, 1994.81 Szejtli, J., Szente, L., Eds. Proceedings of the Eighth International Cyclodextrin Symposium, Budapest,1996; Kluwer Acad. Publ.: Dordrecht, 1996.


The most notable feature of CDs is their ability to accommodate compounds

within their cavities. CDs have different cavity sizes depending on whether they are α, β,

or γ. Figure 1.483,84,85,86,87,88,89,90 shows the structures of some compounds that have been

utilized recently for the formation of complexes involving β-CD derivatives. α-CD,

which is composed of six glucopyranose units has the smallest cavity measuring 4.9Å in

diameter (Figure1.3). β and γ-CDs are made up of seven and eight sugar rings and have

cavity diameters of 6.2 and 7.9Å respectively. The interior of the molecule is

hydrophobic and the exterior is hydrophilic. Each individual glucose ring has one

primary and two secondary hydroxyl groups, which allows for facile derivatization.69 The

hydrophilic nature of the exterior of the CD makes it water soluble, however, through

substitution of the hydroxyl groups this degree of solubility can be altered. The

hydrophobic nature of the interior typically leads to accommodation of relatively

hydrophobic guests within the cavity.91 This accommodation of a molecule within

another molecule is known as complexation and the resulting product is referred to as an

inclusion complex. The surrounding compound is referred to as the host and the

compound that is included in known as the guest. For this reason, inclusion complexes

are often termed host/guest complexes.

82 Torres Labandeira, J.; Villa-Jato, J.; Ed. Proc. of the Ninth Int. Symp. on Cyclodextrins, Santiago dCompostela, Spain, 1998.83 Yu, L.; You, C. J. Phys. Org. Chem. 2001, 14(1), 11.84 Kim, I.; Park, S.; Kim, H. J. Chromatogr., 2000, A 877(1&2), 217.85 Bergamini, J. Belabbas, M.; Jouini, M.; Aeiyach, S.; Lacroix, J.; Chane-Ching, K.; Lacaze, P. J.Electroanal. Chem. 2000, 482(2), 156.86 Shiraishi, Y.; Toshima, N.; Kawamura, T.; Mihori, H.; Shirai, H.; Hirai, H. J. Mol. Catal. A: Chem.1999, 139(2-3), 149.87 Maafi, M.; Aaron, J.; Lion, C. Proc.-Indian Acad. Sci., Chem. Sci. 1998, 110(3), 319.88 Herrmann, W.; Wehrle, S.; Wenz, G. Chem. Commun. 1997, 18, 1709.89 Aithal, K.; Udupa, N. Pharm. Sci. 1996, 2(10), 451.90 Mielcarek, J. Acta Pol. Pharm. 1996, 53(6), 411.91 Szejtli, J.; Osu, T. ed. Comprehensive Supramolecular Chemistry Elsevier Science Ltd; Tarrytown, NY;1996.


Figure 1.4 Names and structures of typical compounds utilized recently in the formationof host-guest complexes with β-CD derivatives.83,84,85,86,87,88,89,90

ONH NH

O

CO2H

(Et)2N N(Et)2

SO3H HN HO3S

NH

N

O

N

F

SH2N

O

O

HS

NH2

O

OH

NO2

OH

OH

HO

O

O

(Me)2N N(Me)2

HN N

N

CO2H

OF

N

O

O

N

O

O

NO2NicardipineCiprofloxacin

(Z)-4,4'-bis(dimethylammoniummethyl)stilbene

2,5 norbornadiene

2,6 naphthalenedicarboxylic acid

4-nitrophenol

homocysteine

4-aminosulfonyl-7-flouro-2,1,3-benzoxadiazole

2-(p-toluidino)naphthalene-6-sulfonic acid

8-anilino-1-naphthalenesulfonic acid

Acridine Red

Rhodamine B


Among the different compounds that can act as host molecules (i.e. urea, thiourea,

and crown ethers to name a few) CDs are preferred for a number of different reasons.92

The first advantage of CD is its relatively nonreactive nature. CD is stable in alkaline

solution, has fairly good resistance to UV and IR light, is thermally stable at up to 270 oC,

and acid hydrolysis only results in nontoxic glucose products. CDs are also nonreducing

and periodate oxidation does not produce formic acid or formaldehyde, which is a

concern for food and drug applications. CDs are also readily available, thoroughly

studied, natural products that have been found to form stoichiometric complexes with a

wide range of molecules. The cavity size is variable depending on whether you use α, β,

or γ-CD, and through modification of the hydroxyl groups the melting and reactive

characteristics can be altered, which make CDs preferable alternatives to other common

host compounds. Table 1.2 gives some of the physical properties of the methylated (1.8)-

α, β, and γ-cyclodextrins.

Table 1.2 Physical properties of methylated (1.8)-α, β, and γ-cyclodextrins as reportedby Wacker Biochem Corporation.93

Methylated(1.8) CyclodextrinProperty

αα ββ γγ

# of glucose rings 6 7 8

Appearance white powder yellowish powder white powder

H2O solubility > 3 g/mL >1.5 g/mL >3 g/mL

Averagemolecular weight

1120 1310 1500

Bulk density 0.2-0.3 g/mL 0.2-0.3 g/mL 0.2-0.3 g/mL

Melting range NA 160-190 °C NA

92 Huang, L.; Tonelli, A. J. M. S.-Rev. Macromol. Chem. Phys. 1998, C38(4), 781.93 www.wacker.com


1.4 Industrial Applications of Cyclodextrins

Today in industry cyclodextrins are incorporated into a variety of items from

chewing gum94 to detergents.91 Cyclodextrin’s ability to incorporate a guest within its

cavity has found usefulness in a multitude of areas.95 Negligible toxicity allows for its

application in everyday products such as shampoo and toothpaste.91,96 CDs have even

been found to be safe enough to be used in food and drug systems. This section will

include a broad but brief introduction into the different ways cyclodextrins and their

ability to accommodate guest molecules are being used today in industry.

Cyclodextrins and their derivatives have found a place in a number of consumer

products and in many industrial processes. They are used to control solubility, mask

agents, and provide stabilization.91,95,96,97 They have also been utilized as general

processing aids and are used to direct chemical reactions, compatibilize materials, and

control volatility. 91,95,96,97

CDs have been found to alter the solubility properties of complexed guests, and

have been utilized to solubilize hydrophobic compounds in aqueous media. Hespiridin is

a compound discovered to be responsible for both a visible cloudiness and bitter taste in

canned oranges.98 Yasumatsuk and coworkers discovered that the addition of CD

noticeably reduced both the cloudiness and bitter taste of the hespiridin.

Increased solubility has also been found to result in increased bioavailability in

drug systems. When administered orally, itraconizole is ineffective due to its insolubility

in the stomach. The insoluble anti-fungal agent is therefore unavailable for absorption

into the body. However, the complex of itraconizole and hydroxypropyl-β-CD shows

increased bioavailability due to its increased solubility.97

94 Sato, Y.; Suzuki, Y.; Ito, K.; Shingawa, T. US Patent 5156866 1992.95 Szetli, J. Inclusion Compounds, vol 3, chapt 11 Academic Press, Orlando, FL; 1984.96 Szetli J. Cyclodextrin Technology Kluwer Academic Pubs, Dordrecht, the Netherlands; 1988.97 Hedges, A. Chem Rev 1998, 98(5), 2035.


Many times when a guest is present in a CD cavity some of the original

compound’s activity is “masked”. 91,95,96,97,99 For example, unwanted flavors in foods can

be masked through complexation with CD as in the previous example with the bitter taste

in oranges. When the compound is complexed, it is isolated and thus prevented from

coming into contact with receptive surfaces. So, in the case of a taste compound, when

the substance is complexed it is unable to interact with the taste buds to relay its bitter

nature. This masking technique has also been used in the case of skin irritants.99

Lotions have been developed in which a fragrant, but irritation-causing component is

complexed with CD in order to limit its direct physical contact with the skin but still

allow for the evolution of the desired fragrance.

Control of volatility and timed release are other areas in which CDs have found a

market. Along with relying on CD as a physical inhibiter to achieve masking of active

components, control of volatility can also be used in the masking of unpleasant odors.

CDs are being used in deodorants and lotions,99 as well as in menstrual products, diapers,

tissues, and paper towels97 to complex and mask unpleasant odors by essentially reducing

their volatility through complexation. Reductions in the volatility of compounds through

complexation have also been used in timed-release applications. CD complexes are used

in laundry detergents as perfume releasers.91 When a detergent containing the

perfume/CD complex is dissolved in water some of the detergent molecules, which are

preferred to occupy the CD cavity over the perfume, replace the perfume and release the

fragrance.

A perfume/CD complex is also being used in dryer sheets as well.81 When a dryer

sheet is added during the drying cycle, the moisture in the environment facilitates transfer

of the CD/fragrance complex from the dryer sheet to the fabric. Some of the complex is

disassociated during this process to give an initial release of fragrance. However, the

majority of the complex remains intact on the fabric, so that when the fabric is moistened

by sweat or another source of moisture the fragrance is released to give the idea of

98 Konno, A.; Misaki, M.; Toda, J.; Wade, T.; Yasumatsu, K. Agric Biol Chem 1986, 46, 2203.99 Vaution, C.; Hutin, M. Cyclodextrins and Their Industrial Uses Duchene, D. ed. Editions de Sante, Paris,France; 1987.


freshness. Timed or prolonged release has also been found useful in the delivery of

vitamin E from hand lotion,99 and the release of perfumes from various toiletries.91

The stabilization of complexed compounds is based on the same premise

introduced above for the masking of a components activity. When a compound is

contained within the cavity of the CD, attack on that compound by other molecules is

severely limited by the shielding of the bulky CD.96 The movement of the guest is also

restricted. It has been found that both thermal and oxidative stabilities have increased

upon complexation with CD. Fish and vegetable oils, which contain easily oxidized

unsaturated fatty acids, have shown increased oxidative stability when complexed with

CD.97 CDs have even been found to decrease photodegradation and increase UV

stabilization.96

In industry, CDs have found invaluable roles as processing aids. CD has been

used in the removal of cholesterol from animal products.100 In one case, warm lard is

stirred over an aqueous layer containing CD. The CD is able to traverse the oil/water

boundary and complex with the cholesterol present in the lard. The cholesterol/CD

complex is then transferred to the aqueous phase where it remains dissolved. The lard is

then removed and processed. This technique has been reported to remove up to 80 % of

the cholesterol present in some animal products. Another processing technique where

CDs are utilized is in some paint processes.101 A thickener, in most paints is used to

obtain a certain consistency and allow them to adhere to the surface. These thickeners,

however, also cause the mixing and processing of the paint to be difficult at times due to

the increase in viscosity associated with their addition. One idea is to complex the

thickener with CD. It was found that the complexed thickener did not increase the

viscosity as much as the uncomplexed species and allowed for easier processing. In the

final steps of the process, another paint component was added that had a greater affinity

for CD and thus displaced the thickener. Once displaced the thickener then exhibited its

normal viscosity increasing properties.

100 Shieh, W.; Hedges, A. US Patent 5371209 1994.101 Lau, W.; Shah, B. US Patent 5376709 1994.


Another more elementary aspect associated with the processing of CD complexes

is the fact that they are solids. When a liquid component is complexed with CD it forms

a solid complex, which is then much easier to handle from an industrial standpoint.96

Generally more precautions are necessary when dealing with liquid components as

opposed to solids. As a result of working with simple dry powders rather than liquids, a

company will generally see a decrease in the costs associated with the handling, packing,

and storage of these compounds.

CDs are also being used to direct specific chemical reactions. As illustrated

previously, a guest complexed with CD can be shielded from attack by reactive species.

However, if the guest is a larger molecule then only a portion of that molecule will be

included within the CD. Only the portion of the molecule that is included within the CD

would be physically shielded from chemical attack. This concept has been utilized in

many ways for highly selective synthesis procedures.91,95,96,97,99 Also, in the same way

that cholesterol is removed from animal lard, CDs can be used to transfer reactive

components between two immiscible liquids and act as a phase transfer catalyst.69,102

Compatibilization is another area where CDs have made their mark. They have

been incorporated into pesticide formulations in order to improve their wettability.96 CDs

also have been incorporated into packaging films for a number of different applications.

When incorporated into some films, CDs have been shown to increase the

biodegradation.96 CDs are also being used in films to control the release and uptake of a

variety of compounds.91 They have been incorporated to produce permiselective films

for food packaging,91 and some have found CD containing films to exhibit controlled

release of a perfume for an extended period of time.91,103

102 Griffiths, D.; Bender, M. Advances in Catalysis Eley, D.; Pines, H.; Weisz, P. Academic Press, NY1973 209.103 Shinbanai, I.; Nakamura, N. US Patent 4356115 1982.


1.5 Research Interests Involving Cyclodextrins

The largest area of interest involving cyclodextrins for both industrial and

academic scientists lies in the research of cyclodextrin based inclusion complexes.97 The

primary interests of the industrial scientist are discussed in the previous section. This

section will focus more on academia. Of course many of these areas overlap, so this

section will outline the more fundamental or purely scientific investigations into the

understanding and impact of cyclodextrin structure, inclusion phenomena in general,

understanding the features that impact inclusion complexation, and various ways in

which host/guest complexes have been utilized to achieve certain research goals.

Though the general structure of cyclodextrin was well established in 1950,97 there

are still substantial research efforts focusing on the study of the structural aspects of

cyclodextrin and its derivatives. Saenger and coworkers104 in the last few years published

a review dealing with both the macro and microscopic structural aspects of the α, β, and

γ-cyclodextrins as well as a number of larger analogues. They included examinations of

not only the conformational features of the individual cyclodextrins but also studies of

macroscopic features such as crystalline structure. Another recent review by

Lipkowitz105outlines the most popular computational modeling programs that have been

utilized in predicting the structure of pure cyclodextrin and a number of inclusion

complexes. However, even in light of the advancements in the computer modeling of

these systems, many scientists91,92,96,101,106,107 rely on the more basic Corey-Pauling-

Koltun molecular molecules that were utilized by Nobel prize laureate Donald. J.

Cram.106

There has been a great deal of effort involved in the study of how substitution of

the hydroxyl groups of cyclodextrin alters fundamental parameters. Modification of

cyclodextrin has been incorporated into a number of research

104 Saenger, W.; Jacob, J.; Gessler, K.; Steiner, T.; Hoffmann, D.; Sanbe, H.; Koizumi, K.; Smith, S.;Takaha, T. Chem. Rev. 1998, 98(5), 1781.105 Lipkowitz, K. Chem. Rev. 1998, 98(5), 1829.106 Cram, D.; Cram, J. Science 1974, 183(4127), 803.107 Borman, S. C&EN 2000, 78(31), 31.


projects.108,109,110,111,112,113,114,115 Derivatization of cyclodextrin has been an important

factor in the success of many projects and has been the topic of a recent review.109

Modification of cyclodextrin has been shown to greatly alter many parameters including

complexation stability and overall solubility. Figure 1.5 demonstrates how the degree of

methylation affects the solubility of cyclodextrin in water.

Figure 1.5 Water solubility of β-cyclodextrin (β-CD), di (DiMe-β-CD), andtrimethylated (TriMe-β-CD) derivatives.92

Given that inclusion complexation is the largest area of interest in cyclodextrin

research, it is of little surprise that the examination of the fundamental parameters of

these complexes has been the primary concern for many scientists. In a recent review

that Rekharsky and Inoue116 organized, they discussed investigations into the

thermodynamics of complexation between cyclodextrin and a number of derivatives with

108 Tian, S.; Zhu, H.; Forgo, P.; D’Souza, V.; J. Org. Chem. 2000, 65(9), 2624.109 Khan, A.; Forgo, P.; Stine, K.; D’Souza, V. Chem. Rev. 1998, 98(5), 1977.110 Harada, A.; Furue, M.; Nozakura, S. Macromolecules 1976, 9(5), 701.111 Szejti, J. Starch 36(12) 1984 429.112 Renard, E.; Deratani, A.; Volet, G.; Sebille, B. Eur. Polym. J. 1997, 33(1), 49.113 Nishiki, M.; Ousaka, Y.; Nishi, N.; Tokura, S.; Sakairi, N. Carbohydrate Polymers 1999, 39, 1.114 Bachmann, F.; Hopken, J.; Kohli, R.; Lohmann, D.; Schneider, J. J. Carbohydrate Chem.1998, 17(9),1359.115 Fulton, D.; Stoddart, J. F. Org. Lett. 2000, 2(8), 1113.116 Rekharsky, M.; Inoue, Y. Chem. Rev. 1998, 98(5), 1875.


a multitude of guest compounds under different conditions. Conners,117 Setjexi,96 and

Bender69 are but a few who have proposed that complexation strength in cyclodextrins

results primarily from hydrophobic-hydrophobic interactions between host and guest.

The majority of cyclodextrin complexation studies are done in aqueous environments

because in a non-aqueous solution the solvent may actively compete with the desired

guest molecule to form an inclusion complex with cyclodextrin.

Cyclodextrin, cyclodextrin derivatives, and cyclodextrin based complexes have

been studied by many techniques including NMR and 2D NMR

analysis,118,119,120,121,122,123,124,125,126,127,128 calorimetry and TGA,97 X-ray methods,92,129,130

electric field pulse techniques,131 volumetric techniques,132 electron microscopy,133,134

circular dichroism,135 and electron paramagnetic resonance(ESR&EPR)136,137 to name a

few. There has been extensive work in the area of NMR analysis of cyclodextrin and its

complexes,118 and it is the most accepted technique utilized in confirming an inclusion

complex with cyclodextrin. Cyclodextrin’s rigid ring structure allows for designation of

protons located on either the exterior or interior of the truncated cone.69 When a guest is

accommodated within the cyclodextrin cavity there is an NMR shift in several of the

117 Connors, K. Chem. Rev. 1997, 97(5), 1325.118 Schneider, H.; Hacket, F.; Rudiger, V. Chem. Rev. 1998, 98(5), 1755.119 Inoue, Y.; Kuan, F.; Takahashi, Y.; Chujo, R. Prelim. Comm. 1984.120 Thakkar, A.; Demarco, P. J. Pharm. Sci. 1971, 60(4), 652.121 Demarco, P.; Thakkar, A. Chem. Comm. 1970 2.122 Harada, A.; Furue, M.; Nozakura, S. Polymer J. 1981, 13(8), 779.123 Colson, P.; Jennings, H.; Smith, I. J. Am. Chem. Soc. 1974, 96(26), 8081.124 Tezuka, Y.; Hermawan, I. Carbohydrate Research 1994, 260, 181.125 Fronza, G.; Mele, A.; Redenti, E.; Ventura, P. J. Pharm. Sci.1992, 81(12), 1162.126 Hirai, H.; Shiraishi, Y.; Mihori, H.; Saito, K.; Kawamura, T. Polymer J. 1996, 28(1), 91.127 Perez-Martinez, J.; Gines, J.; Morillo, E.; Moyano, J. J Inclusion. Phenomena and Macrocyclic Chem.2000, 37, 171.128 Hamai, S.; Takahashi, A. J Inclusion. Phenomena and Macrocyclic Chem. 2000, 37, 197.129 Hirotsu, K.; Higuchi, T.; Fujita, K.; Ueda, T.; Shinoda, A.; Imoto, T.; Tabushi, I. J. Org. Chem. 1982,47(6), 1143.130 Rusa, C.; Luca, C.; Tonelli, A. Macromolecules 2001, 34(5), 1318.131 Sasaki, M.; Ikeda, T.; Mikami, N.; Yasunaga, T. J. Phys. Chem. 1983, 87, 5.132 Wilson, L.; Verrall, R. J. Phys. Chem. B 2000, 104, 1880.133 Hodi, K.; Szeged, K. Starch 1985, 37(6), 205.134 Meyer, E.; Islam, M.; Lau, W.; Ou-Yang, H. Langmuir 2000, 16(13), 5519.135 Suzuki, M.; Fenyvesi, E.; Szilasi, M.; Szejtli, J.; Kajtar, M.; Zsadon, B.; Sasaki, Y. J. InclusionPhenomena 1984, 2, 715.136 Sun, J.; Liu, Y.; Chen, D.; Zhang, Q. J. Physics and Chemistry of Solids 2000, 61, 1149.137 Lucarini, M.; Pedulli, G. J. Org. Chem. 2000, 65(9), 2723.


protons on the interior of the cyclodextrin and in the protons of the guest within the

cavity.96 A relatively large shift in the interior protons as opposed to the exterior has

been accepted as means of inclusion complex confirmation.

Inclusion complex formations involving cyclodextrins have been utilized in

catalysis of reactions. They have been incorporated into biomimetic reactions where

cyclodextrin acts as an enzymatic model.104 The first instance of a cyclodextrin being

used to mimic enzymatic activity was in Cramer and coworkers73 research during the

1950s. Since then advances have been made and the cyclodextrins have been derivatized

in order to more accurately mimic biological catalysts.68 There has also been much

interest in cyclodextrins as dual phase catalysts.138,139,140,141,142,143 Once a guest is

accommodated within the host cavity several of its parameters, including solubility, are

altered. This alteration in solubility allows for the guest compound to be transferred

between phases where it is then available to react. The observation of increased

availability of a guest also has been utilized in drug delivery

systems.144,145,146,147,148,149,150,151 Cyclodextrin’s potential in drug carrier systems is

another area of great interest from an industrial and academic viewpoint. Factors such as

skin permeation,152 increased photostability,99,153 and water solubility154,155 are but a few

of the areas being investigated.

138 Breslow, R.; Dong, S. Chem. Rev. 1998, 98(5), 1997.139 Ryoshi, H.; Kunieda, N.; Kinoshita, M. Makromol. Chem. 1986, 187, 263.140 Tilloy, S.; Bertoux, F.; Mortreux, A.; Monflier, E. Catalysis Today 1999, 48, 245.141 Toguchi, H.; Kunieda, N.; Kinoshita, M. Makromol. Chem. 1983, 184, 925.142 Taguchi, H.; Kunieda, N.; Kinoshita, M. Makromol. Chem., Rapid Commun. 1982, 2, 495.143 Taguchi, H.; Kunieda, N.; Shiode, S.; Kinoshita, M. Makromol. Chem., Rapid Commun. 1982, 3, 395.144 Uekama, K.; Hirayama, F.; Irie, T. Chem. Rev. 1998, 98(5), 2045.145 Gonzalez, H.; Hwang, S.; Davis, M. Bioconjugate Chem. 1999, 10(6), 1068.146 Bibby, D.; Davies, N.; Tucker, I. J. Microencapsulation 1998, 15(5), 629.147 Duchene, D.; Wouessidjewe, D.; Ponchel, G. Journal of Controlled Release 1999, 62, 263.148 Wulff, M.; Alden, M. European Journal of Pharmaceutical Sciences 1999, 8, 269.149 Bibby, D.; Davies, N.; Tucker, I. International Journal of Pharmceutics 1999, 187, 243.150 Miro, A.; Quaglia, F.; Calignano, A.; Barbato, F.; Capello, B.; Rotonda, M. S. T. P. Pharma Sciences2000, 10(2), 157.151 Ooya, T.; Yui, N. Critical Reviews in Therapeutic Drug Carrier Systems 1999, 16(3), 289.152 Lopez, R.; Collett, J.; Bentley, V. International Journal of Pharmaceutics 2000, 200, 127.153 Brisaert, M.; Plaizier-Vercammen, J. International Journal of Pharmaceutics 2000, 199, 49.154 Szeman, J.; Fenyvesi, E.; Szejtli, J.; Ueda, H.; Machida, Y.; Nagai, T. Journal of Inclusion Phenomena1987, 5, 427.155 Fenyvesi, E. Journal of Inclusion Phenomena 1988, 6, 537.


Cyclodextrins are also used for the mediation of specific organic

reactions.156,157,158,159,160,161 Not only does formation of a host/guest complexation alter

parameters such as solubility, but also physical inclusion of a guest within a host offers a

significant amount of steric shielding of the guest molecule. For this reason,

cyclodextrins have been used in the area of selective synthesis. 2,6-

naphthalenedicarboxylic acid for example is an important monomer for liquid crystalline

polymer synthesis. Synthesis of the 2,6 diacid monomer can be difficult due to the

multiple reactive sites throughout the naphthalene ring leading to a range of products.

Hirai and coworkers156 found that if the naphthalene reactant was first included within

cyclodextrin then the yields of the 2,6 product were greatly increased. The cyclodextrin

host sterically shielded the undesirable reaction sites on the naphthalene ring leading to

greater selectivity.

Another area of academic research involving the use of cyclodextrin is in the field

of rotaxane and polyrotaxane chemistry. There have been a few reviews162,163 along with

a number of research papers164,165,166,167,168,169,170,171,172 that have been published recently

concerning cyclodextrins in this field of chemistry. In fact, the review by Stoddart and

Nepogodiev162 deals solely with cyclodextrin based rotaxane structures. Harada and

156 Shiraishi, Y.; Toshima, N.; Kawamura, T.; Mihori, H.; Shirai, H.; Hirai, H. Journal of MolecularCatalysis 1999, 139, 149.157 Takahashi, K. Chem. Rev. 1998, 98(5), 2013.158 Enmanji, K. J. Poly. Sci. Polym. Chem. Ed. 1988, 26, 1465.159 Hirai, H.; Mihori, H.; Terakado, R. Makromol. Chem., Rapid Commun. 1993, 14, 439.160 Kunieda, N.; Yamane, S.; Kinoshita, M. Makromol. Chem., Rapid Commun. 1985, 6, 305.161 Seo, T.; Kajihara, T.; Iijima, T. Makromol. Chem. 1987, 188, 1295.162 Nepogodiev, S.; Stoddart, J. Chem. Rev. 1998, 98(5), 1959.163 Amabilino, D.; Stoddart, J. Chem. Rev. 1995, 95(8), 2725.164 Shigekawa, H.; Miyake, K.; Sumaoka, J.; Harada, A.; Komiyama, M. J. Am. Chem. Soc. 2000, 122(22),5411.165 Kawaguchi, Y.; Harada, A. Org. Lett. 2000, 2(10), 1353.166 Iijima, T.; Uemura, T.; Tsuzuku, S.; Komiyama, J. Journal of Polymer Science: Polymer PhysicsEddition 1978, 16, 793.167 Kawaguchi, Y.; Harada, A. J. Am. Chem. Soc. 2000, 122, 3797.168 Harada, A.; Kawaguchi, Y.; Nishiyama, T.; Kamachi, M. Macromol. Rapid Commun. 1997, 18, 535.169 Okada, M.; Kamachi, M.; Harada, A. Macromolecules 1999, 32(21), 7202.170 Amiel, C.; Sebille, B. Advances in Colloid and Interface Science 1999, 79, 105.171 Gosselet, N.; Borie, C.; Amiel, B.; Sebille, B. J. Dispersion Science and Technology 1998, 19(6&7),805.172 Han, S.; Yoo, M.; Sung, Y.; Lee, Y.; Cho, C. Macromol. Rapid Commun. 1998, 19, 403.


coworkers168 are studying cyclodextrin-based polyrotaxanes and have proposed a

controversial structure in which a poly(ε-caprolactone)-α-cyclodextrin complex was said

have formed a cyclodextrin based “molecular tube” when the polymer backbone was

selectively decomposed. Also, more recently, scanning tunneling microscopy has

allowed for direct observation of a single cyclodextrin polymer pseudorotaxane164 and

the possibility of a “molecular shuttle” type system has been reported.164

Cyclodextrins have also been used for selective recognition of components. The

specific cavity size of cyclodextrins has been used to selectively incorporate compounds

based on chirality,173,174 molecular weight,175 and steric bulk.176 This aspect of

cyclodextrin complexes has been used in selective complexation and removal of water

born contaminants.99,177,178,179,180,181,182,183 The fluorescent properties of compounds have

been examined before and after complexation and in some cases an increase in

fluorescent intensity is observed.184,185 Films containing cyclodextrin have also gained

their share of attention. Studies involving anion permeation186 and other selective

diffusion187 have been found in the literature.

173 Rekharsky, M.; Inoue, Y. J. Am. Chem. Soc. 2000, 122(18), 4418.174 Ravi, P.; Divakar, S. J. M. S. Pure Appl. Chem. 1995, A32(5), 1061.175 Rusa, C.; Tonelli, A. Macromolecules 2000, 33(5), 1813.176 Harada, A.; Adachi, H.; Kawagichi, Y.; Kamachi, M. Macromolecules 1997, 30(17), 5181.177 Bugler, J.; Sommerdijk, N.; Visser, A.; Hoek, A.; Nolte, R.; Engbersen, J.; Reinhoudt, D. J. Am. Chem.Soc. 1999, 121(1), 28.178 Monflier, E.; Tilloy, S.; Meliet, C.; Mortreux, A.; Fourmentin, S.; Landy D.; Surpateanu, G. New J.Chem. 1999, 23, 469.179 Uemura, T.; Moro, T.; Komiyama, J.; Iijima, T. Macromolecules 1979, 12(4), 737.180 Wilson, E. Chemical & Engineering News 1999, 77(5), 32.181 Crini, G.; Bertini, S.; Torri, G.; Naggi, A.; Sforzini, D.; Vecchi, C.; Janus, L.; Lekchiri, Y.; Morcellet,M. Journal of Applied Polymer Science 1998, 68, 1973.182 Spencer, J.; He, Q.; Ke, X.; Wu, Z.; Fetter, E. Journal of Solution Chemistry 1998, 27(11), 1009.183 Murai, S.; Imajo, S.; Inumaru, H.; Takahashi, K.; Hattori, K. Journal of Colloid and Interface Science1997, 190, 488.184 Grabner, G.; Rechthaler, K.; Mayer, B.; Kohler, G.; Rotkiewicz, K. J. Phys. Chem. A 2000, 104(7),1365.185 Hirasawa, T.; Maeda, Y.; Kitano, H. Macromolecules 1998, 31(14), 4480.186 Sata, T.; Kawamura, K. Journal of Membrane Science 2000, 171, 97.187 Hirai, H.; Komiyama, M.; Yamamoto, H. Journal of Inclusion Phenomena 1984, 2, 655.


1.6 Cyclodextrin Mediation of Polymer Synthesis

The concept of CD mediation of aqueous polymerizations is a relatively new one.

There are only a few groups working in this area including Ritter and coworkers at the

University of Mainz, and Rimmer and coworkers at Lancaster University. Rimmer and

coworkers have published an article where they used β-CD as an emulsifier in the

heterogeneous polymerization of n-butyl methacrylate.188 They examined the effect of

CD addition on these emulsion type polymerization systems both with and without

additional ionic emulsifier. It was found that in systems where the typical ionic

emulsifier was included that the addition of cyclodextrin had little effect on the number

average molecular weight, molecular weight distribution, or average particle size of the

latex. In systems without surfactant, however, addition of cyclodextrin was shown to

increase the molecular weights obtained.

Rimmer and coworkers report that n-butyl methacrylate can form a 30,000

number average molecular weight polymer in the absence of any type of surfactant or

stabilizer.188 In the absence of surfactant, one would normally expect a hydrophobic

monomer such as n-butyl methacrylate to give very little polymer formation; however,

the limited water solubility of the monomer allows for initiation and limited propagation

in aqueous solution. The resulting polymer was observed to completely coagulate

producing an uncontrolled polymer with molecular weight distributions from 9-13. The

addition of cyclodextrin resulted in a decrease in molecular weight distribution and an

increase in molecular weight compared to the systems without cyclodextrin or ionic

surfactant. Also cyclodextrin was shown to increase the stability of the particles formed.

Unfortunately however, systematic variations of cyclodextrin concentration

resulted in erratic data. Though higher molecular weights are achieved by addition of

cyclodextrin, they are much lower than those obtained by the ionic surfactant, and the

molecular weight distributions are much larger (4.0-9.7) and also not systematic. The

article presents analysis of the transmission electron microscopy of some of the particles

produced from the “emulsion polymerization” with cyclodextrin as surfactant. They


report narrow particle size distribution, but admit that the normal control of particle size

afforded by conventional emulsion polymerization is not present in these

polymerizations. The average particle sizes seem to be erratic as well, and are

independent of cyclodextrin concentration.

Ritter and coworkers are the second group involved in cyclodextrin mediation of

polymerizations. Their first interests were in cyclodextrin based side chain rotaxanes,189

but they soon discovered and utilized the solubility altering properties of cyclodextrins

towards guest compounds to mediate the polymerizations of phenyl and cyclohexyl

methacrylates190 In this article they complexed the monomers with cyclodextrin and

subsequently dissolved them in water and polymerized the monomer with a water soluble

free radical initiator. The results presented however, were preliminary and incomplete.

The following publication offered a more detailed look at the mechanism involved in the

process.191 In this case several acrylamides were polymerized by first complexing them

with cyclodextrin, dissolving the complexes in water and then initiating polymerization

with a water soluble initiator. A mechanism involving the detreading of cyclodextrin

from the polymer as it propagates was tentatively suggested. However, this

communication concentrated mainly on the characterization of the complexes. Thin layer

chromatography, 1H NMR at various temperatures, and mass spectrometry were used to

support complexation formation.

The corresponding full publication on this topic was published in Macromolecules

the following year.192 This article also concentrated on complex characterization adding

two dimensional NMR and differential scanning calorimetry to help support complex

formation. The group also has published a series of communications in which this

technique was used to polymerize a variety of monomer including n-butyl acrylate and

isobornyl acrylate,193 methyl methacrylate and styrene,194 and several oxaline-

188 Rimmer, S.; Tattersall, P. Polymer 1999, 40, 6673.189 Born, M.; Ritter, H. Macromol. Rapid Commun. 1996, 17, 197.190 Jeromin, J.; Ritter, H. Macromol. Rapid Commun. 1998, 19, 377.191 Jeromin, J.; Noll, O.; Ritter, H. Macromol. Chem. Phys. 1998, 199, 2641.192 Jeromin, J.; Ritter, H. Macromolecules 1999, 32(16), 5236.193 Glockner, P.; Ritter, H. Macromol. Rapid Commun. 1999, 20, 602.


functionalized monomers.195 In the work published by Ritter and coworkers thus far the

cyclodextrin/monomer complexes have been verified by reported shifts in the 1H NMR of

the guest molecules. However, these shifts are only typically on the order of 0.05 ppm in

all cases save for the oxaline-functionalized compounds. It is unclear as to the degree of

error or the reproducibility that is associated with these shift measurements.

Nevertheless, the Ritter group has done a substantial amount of work in this area. In the

past year, there have been two publications in Macromolecules dealing with these

cyclodextrin-mediated polymerizations in which addition of a chain transfer agent was

examined196,197 and where copolymerizations between the cyclodextrin/hydrophobic

monomer complexes and the water-soluble n-isopropylacrylamide were attempted.

194 Storsberg, J.; Ritter, H. Macromol. Rapid Commun. 2000, 21, 236.195 Fischer, M.; Ritter, H. Macromol. Rapid Commun. 2000, 21, 142.196 Glockner, P.; Metz, N.; Ritter, H. Macromolecules 2000, 33(11), 4288.197 Casper, P.; Glockner, P.; Ritter, H. Macromolecules 2000, 33(12), 4361.

Phillip H. Madison, IV Chapter II: Preparation and Characterization of Cyclodextrin/Methacrylate Complexes

39

Chapter II: Preparation and Characterization ofCyclodextrin/ Methacrylate Complexes

Abstract

Hydrophobic methacrylic monomers were complexed with methylated(1.8)-β-

cyclodextrin (MeCD). t-Butyl methacrylate (tBuMA), n-butyl methacrylate (nBuMA),

cyclohexyl methacrylate (CMA), and 2-ethylhexyl methacrylate (2EHMA) and MeCD

were dissolved in chloroform and stirred for one or six days. Two-dimensional NMR

techniques were used to analyze MeCD in order to confirm the degree of methylation and

determine peak assignments. Thin layer chromatography (TLC) also was used to

examine the complexes. The purity and thermal stability of the monomers and MeCD

were analyzed by 1H NMR and thermogravimetric analysis (TGA). 1H NMR and TGA

also were used to determine the ratios of monomer to MeCD in the resulting complexes

and confirm complexation. Complexes were shown to have molar ratios of monomer to

MeCD as high as 0.72/1.00 and were water soluble in all cases.


40

2.1 Introduction

Cyclodextrin (CD) has found homes in both the areas of academia and industry.

Their ability to form host guest complexes has been utilized in consumer products

ranging from chewing gum1 to detergent2 and has been incorporated into chemical

processes3,4 and drug delivery systems.5,6,7,8,9,10,11,12 From an academic standpoint CDs

have offered pure research opportunities including investigations of novel synthetic

strategies to examinations of more fundamental parameters. For example, CDs have been

used as transports for dual phase synthesis,13,14,15 stereoselective synthesis,16,17,18 and

discriminating complexation of water born contaminants, including substituted phenols,19

other benzene derivatives,20 a series of organic esters,21 and ionic surfactants.22 They

have also been utilized in the area of rotaxane chemistry.23,24,25,26

1 Sato, Y.; Suzuki, Y.; Ito, K.; Shingawa, T. US Patent 5156866 1992.2 Szejtli, J.; Osu, T. ed. Comprehensive Supramolecular Chemistry Elsevier Science Ltd; Tarrytown, NY;1996.3 Shieh, W.; Hedges, A. US Patent 5371209 1994.4 Lau, W.; Shah, B. US Patent 5376709 1994.5 Uekama, K.; Hirayama, F.; Irie, T. Chem. Rev. 1998, 98(5), 2045.6 Gonzalez, H.; Hwang, S.; Davis, M. Bioconjugate Chem. 1999, 10(6), 1068.7 Bibby, D.; Davies, N.; Tucker, I. J. Microencapsulation 1998, 15(5), 629.8 Duchene, D.; Wouessidjewe, D.; Ponchel, G. Journal of Controlled Release 1999, 62, 263.9 Wulff, M.; Alden, M. European Journal of Pharmaceutical Sciences 1999, 8, 269.10 Bibby, D.; Davies, N.; Tucker, I. International Journal of Pharmceutics 1999, 187, 243.11 Miro, A.; Quaglia, F.; Calignano, A.; Barbato, F.; Capello, B.; Rotonda, M. S. T. P. Pharma Sciences2000, 10(2), 157.12 Ooya, T.; Yui, N. Critical Reviews in Therapeutic Drug Carrier Systems 1999, 16(3), 289.13 Monflier, E. Recent Res. Dev. Org. Chem. 1998, 2(Pt. 2), 623.14 Monflier, E.; Tilloy, S.; Blouet, E.; Barbaux, Y.; Mortreux, A. J. Mol. Catal. A: Chem. 1996, 109(1), 27.15 Monflier, E.; Tilloy, S.; Fremy, G.; Barbaux, Y.; Mortreux, A. Tetrahedron Lett. 1995, 36(3), 387.16 Takahashi, K. Chem. Rev. 1998, 98(5), 2013.17 Shiraishi, Y.; Toshima, N.; Kawamura, T.; Mihori, H.; Shirai, H.; Hirai, H. Journal of MolecularCatalysis 1999, 139, 149.18 Hirai, H.; Mihori, H.; Terakado, R. Makromol. Chem., Rapid Commun. 1993, 14, 439.19 Wilson, E. Chemical & Engineering News 1999, 77(5), 32.20 Crini, G.; Bertini, S.; Torri, G.; Naggi, A.; Sforzini, D.; Vecchi, C.; Janus, L.; Lekchiri, Y.; Morcellet, M.Journal of Applied Polymer Science 1998, 68, 1973.21 Spencer, J.; He, Q.; Ke, X.; Wu, Z.; Fetter, E. Journal of Solution Chemistry 1998, 27(11), 1009.22 Murai, S.; Imajo, S.; Inumaru, H.; Takahashi, K.; Hattori, K. Journal of Colloid and Interface Science1997, 190, 488.23 Nepogodiev, S.; Stoddart, J. Chem. Rev. 1998, 98(5), 1959.24 Amabilino, D.; Stoddart, J. Chem. Rev. 1995, 95(8), 2725.25 Shigekawa, H.; Miyake, K.; Sumaoka, J.; Harada, A.; Komiyama, M. J. Am. Chem. Soc. 2000, 122(22),5411.


41

Cyclodextrin, cyclodextrin derivatives, and cyclodextrin based complexes have

been studied by many techniques including NMR and 2D NMR

analysis,27,28,29,30,31,32,33,34,35,36,37 calorimetry and TGA,38 X-ray methods, 39,40,41 electric

field pulse techniques,42 volumetric techniques,43 electron microscopy,44,45 circular

dichroism,46 and electron paramagnetic resonance(ESR&EPR)47,48 to name a few. There

has been extensive work in the area of NMR analysis of cyclodextrin and its complexes,27

and it is the most accepted technique utilized in confirming an inclusion complex with

cyclodextrin. Cyclodextrin’s rigid ring structure allows for designation of protons

located on either the exterior or interior of the truncated cone.49 When a guest is

accommodated within the cyclodextrin cavity, there is an NMR shift in several of the

protons on the interior of the cyclodextrin and in the protons of the guest within the

cavity.50 A relatively large shift in the interior protons as opposed to the exterior has

been accepted as means of inclusion complex confirmation.

26 Kawaguchi, Y.; Harada, A. Org. Lett. 2000, 2(10), 1353.27 Schneider, H.; Hacket, F.; Rudiger, V. Chem. Rev. 1998, 98(5), 1755.28 Inoue, Y.; Kuan, F.; Takahashi, Y.; Chujo, R. Prelim. Comm. 1984.29 Thakkar, A.; Demarco, P. J. Pharm. Sci. 1971, 60(4), 652.30 Demarco, P.; Thakkar, A. Chem. Comm. 1970 2.31 Harada, A.; Furue, M.; Nozakura, S. Polymer J. 1981, 13(8), 779.32 Colson, P.; Jennings, H.; Smith, I. J. Am. Chem. Soc. 1974, 96(26), 8081.33 Tezuka, Y.; Hermawan, I. Carbohydrate Research 1994, 260, 181.34 Fronza, G.; Mele, A.; Redenti, E.; Ventura, P. J. Pharm. Sci. 1992, 81(12), 1162.35 Hirai, H.; Shiraishi, Y.; Mihori, H.; Saito, K.; Kawamura, T. Polymer J. 1996, 28(1), 91.36 Perez-Martinez, J.; Gines, J.; Morillo, E.; Moyano, J. J Inclusion. Phenomena and Macrocyclic Chem.2000, 37, 171.37 Hamai, S.; Takahashi, A. J Inclusion. Phenomena and Macrocyclic Chem. 2000, 37, 197.38 Hedges, A. Chem Rev 1998, 98(5), 2035.39 Huang, L.; Tonelli, A. J. M. S.-Rev. Macromol. Chem. Phys. 1998, C38(4), 781.40 Hirotsu, K.; Higuchi, T.; Fujita, K.; Ueda, T.; Shinoda, A.; Imoto, T.; Tabushi, I. J. Org. Chem. 1982,47(6), 1143.41 Rusa, C.; Luca, C.; Tonelli, A. Macromolecules 2001, 34(5), 1318.42 Sasaki, M.; Ikeda, T.; Mikami, N.; Yasunaga, T. J. Phys. Chem. 1983, 87, 5.43 Wilson, L.; Verrall, R. J. Phys. Chem. B 2000, 104, 1880.44 Hodi, K.; Szeged, K. Starch 1985, 37(6), 205.45 Meyer, E.; Islam, M.; Lau, W.; Ou-Yang, H. Langmuir 2000, 16(13), 5519.46 Suzuki, M.; Fenyvesi, E.; Szilasi, M.; Szejtli, J.; Kajtar, M.; Zsadon, B.; Sasaki, Y. J. InclusionPhenomena 1984, 2, 715.47 Sun, J.; Liu, Y.; Chen, D.; Zhang, Q. J. Physics and Chemistry of Solids 2000, 61, 1149.48 Lucarini, M.; Pedulli, G. J. Org. Chem. 2000, 65(9), 2723.49 Bender, M.; Komiyama, M. Cyclodextrin Chemistry Springer Verlag,, NY 1978.50 Szetli J. Cyclodextrin Technology Kluwer Academic Pubs, Dordrecht, the Netherlands; 1988.


42

This report describes the formation of host guest complexes of t-butyl

methacrylate, n-butyl methacrylate, cyclohexyl methacrylate, and 2-ethylhexyl

methacrylate with methylated(1.8)-β-cyclodextrin, which will ultimately be used in

aqueous polymerizations. Monomer to cyclodextrin ratios in the complexes were

elucidated using TGA and NMR analysis. The dependence of these ratios on reaction

time also was investigated. Also, NMR, TGA, and CPK modeling were performed and

analyzed in concert to support the formation of the respective monomer/MeCD

complexes.

2.2 Experimental

Purification: All monomers were purchased from Aldrich and used as received unless

otherwise stated. MeCD was generously donated by Wacker-Chemie and was used as

received. Monomers were vacuum distilled (0.5 mm Hg) from CaH2 using the freeze-

thaw method to degas the monomer and stored at –25 °C under nitrogen.

Complexation: Complexations of tBuMA, 2-EHMA, nBuMA, and CMA were

preformed in 200 mL of chloroform with concentrations of approximately 0.04 M of both

MeCD and monomer. Approximately 10.0 g (7.6 mmol) of MeCD and a molar

equivalent of monomer were added to 200 mL of chloroform in a 500 mL erlenmeyer

flask. The solution was stirred for 1-6 days at room temperature. Chloroform was then

removed using a rotoevaporator and the complex was dried in vacuo at 70 °C for 24

hours. Isolated yields ranged from 90-96 % and ratios of monomer to MeCD ranged

from 0.50/1.00 to 0.75/1.00.

Characterization: All NMR spectra were obtained in CDCl3 using a Varian 400 MHz

NMR. Thermogravimetric analysis (TGA) was utilized under N2 atmosphere using a

Perkin-Elmer TGA7 and heating cycles varied.


43

Figure 2.1 Cyclodextrin size and structure.52

2.3 Results and Discussion

It has been well documented that a good fit between a host and a guest compound

is crucial to the formation of inclusion compounds.49,50 It is intuitive that if the guest is

too large to be accommodated within the desired cavity then an inclusion complex can

not be formed, but also it appears guests that are too small tend to form only weak

complexes. This phenomenon is easily explained by considering the increased distance

between host and guest when the guest is small. Since the primary interactions leading to

complex formation are the hydrophobic-hydrophobic interactions between host and guest

and these forces are greatly dependent on distance, it is reasonable to conclude that a

looser fit of the guest within the host would produce a weaker complex strength.

Therefore, in designing a host/guest system one must take the relative molecular sizes of

host and guest into consideration. One of the advantages of CDs is that they are readily

synthesized in a variety of sizes. Figure 2.1 gives the cavity dimensions of the three most

common CDs and their respective chemical structures. The cyclodextrin utilized in this


44

study was a methylated derivative of beta-cyclodextrin (1.8 out of 3.0 hydroxyl groups

present on each glucose ring were converted to methoxy groups). The beta-cyclodextrin

was used for this project because its cavity size was shown to readily accommodate the

monomers examined. CPK modeling was used to examine the feasibility of inclusion

complexation for the monomers utilized in this project. CPK models have been used

extensively to examine the space filling characteristics of compounds.2,51,52,53,54,55

Figures 2.2-4 show CPK models of beta-cyclodextrin and several of the monomers

utilized in this study. This modeling study indicated that the cavity size of the beta-CD

was large enough to accommodate the monomers utilized, but that the fit is tight enough

to allow for host guest interaction of sufficient strength.

51 Bender, M.; Komiyama, M. Cyclodextrin Chemistry Springer Verlag,, NY 1978.52 Huang, L.; Tonelli, A. J. M. S.-Rev. Macromol. Chem. Phys. 1998, C38(4), 781.53 Szetli J. Cyclodextrin Technology Kluwer Academic Pubs, Dordrecht, the Netherlands; 1988.54 Cram, D.; Cram, J. Science 1974, 183(4127), 803.55 Borman, S. C&EN 2000, 78(31), 31.


45

Figure 2.2 CPK models of t-butyl methacrylate and β-cyclodextrin in free and complexed form.

Figure 2.3. CPK models of cyclohexyl methacrylateand β-cyclodextrin in free and complexed form.

Figure 2.4 CPK models of 2-ethylhexyl methacrylateand β-cyclodextrin in free and complexed form.


46

Scheme 2.1 Preparation of monomer/methylated(1.8)-β-cyclodextrin complexes

Scheme 2.1 shows the procedure for formation of the complexes. Complexation

times of six days were used initially as previously described by Ritter et al,56 however, it

became clear that this length of time was not required. To test the effect of time on the

ratio of monomer to CD in the complex, experiments were run allowing the chloroform

solution containing CD and either tBuMA or CMA to stir for one or six days. The results

from this study are presented in Table 2.1. It was found that the ratio of monomer to CD

produced from either one or six days of stirring varied only slightly.

56 Jeromin, J.; Noll, O.; Ritter, H. Macromol. Chem. Phys. 1998, 199, 2641.

R' = H or Me

7

CHCl324 hrs

25 oC O

O

RO

O

R

+O

O

OR'R'O

OR'

R = or or or


47

Table 2.1 Comparison of results from complexation procedures that involved stirring foreither one or six days in chloroform.

MONOMER NUMBER OF DAYS RATIO MONOMER:MeCDa

tBuMA 6 0.60:1.00

tBuMA 1 0.65:1.00

CMA 6 0.72:1.00

CMA 1 0.70:1.00

a- ratios determined using Varian 400 MHz 1H NMR in CDCl3 Calculated from the resonances of the twoprotons of the monomer at approximately 5.5 and 6.1 ppm were compared to the MeCD proton at 5.0 ppm

1H NMR was performed on all monomers, CD, and monomer/CD complexes.

The integrations and peak designations are shown in Figures 2.5-13. Two-dimensional

NMR was also used to confirm the peak designations for the MeCD and the degree of

methoxy substitution. It was found that the distribution of methoxy groups is random

between the single primary and two secondary hydroxyl groups present in each glucose

ring. Due to this random derivatization of the primary and secondary hydroxyl groups,

the 1H NMR at shifts between 3.0-4.0 ppm are overlapped making integrations and

assignments unreliable. Through 2D NMR analysis, the peaks between 4.8-5.2 ppm were

found to be the single proton bound to the carbon alpha to both hetero oxygen atoms in

the glucose ring. This proton is broad and split due to long-range association with each

of the three randomly substituted hydroxyl groups per ring. Also, the comparison of the


48

Figure 2.5 1H NMR of methylated(1.8)-β-cyclodextrin in chloroform.


49

Figure 2.6 1H NMR of 2-ethylhexyl methacrylate in chloroform.


50

Figure 2.7 1H NMR of 2-ethylhexyl methacrylate (top), MeCD (middle), and the subsequent complex in chloroform (bottom).


51

Figure 2.8 1H NMR of cyclohexyl methacrylate in chloroform.


52

Figure 2.9 1H NMR of cyclohexyl methacrylate (top), MeCD (middle), and the subsequent complex in chloroform (bottom).


53

Figure 2.10 1H NMR of n-butyl methacrylate in chloroform.


54

Figure 2.11 1H NMR of n-butyl methacrylate (top), MeCD (middle), and the subsequent complex in chloroform (bottom).


55

Figure 2.12 1H NMR of t-butyl methacrylate in chloroform.


56

Figure 2.13 1H NMR of t-butyl methacrylate (top), MeCD (middle), and the subsequent complex in chloroform (bottom).


57

integration of the area between 4.8-5.2 ppm to the area between 3.0-4.0 ppm is consistent

with the structure of CD in which 1.8/3.0 of the hydroxyl groups are methoxy

substituents.

With the peak designations confirmed, 1H NMR was then used to determine the

ratio of monomer to CD in the complexes. The integrations of the single proton of CD

(4.8-5.2 ppm) was compared to the unsaturated protons of each monomer (5.4-6.1 ppm)

and the ratios were subsequently calculated. 1H NMR has also been reported as a means

to confirm complexation.2 Shifts in the protons of both the monomer and CD have been

reported and the degree of shift in the interior protons of the CD compared to shifts in the

exterior protons have been used to support inclusion complexation. However, most of

these measurements are done in aqueous solution. It has been reported that in chloroform

and other more non-polar solvents complexation strengths are weak and the equilibrium

between inclusion complex and free species lies mainly towards the uncomplexed

species.51 In more non-polar solvents, the host and guest are only complexed to a small

degree and thus the shifts that occur in polar solvents are not seen. In this study MeCD

was also examined in water and DMSO but it was found that the peak separation of the

region between 3.0-4.0 ppm was not sufficient enough to make accurate assignments.

Therefore shifts of peaks are of little significance since they could not be identified as

being on the interior or exterior of the CD.

TGA was also utilized to determine the ratio of monomer to MeCD in the

resulting complex from Scheme 2.1. First, TGA of pure, dry MeCD was performed as a

reference. The cyclodextrin/monomer complex was carefully dried to remove any

residual solvent and water and was analyzed under similar conditions. Figure 2.15

illustrates the thermal stabilities of the CMA/MeCD complex (0.72/1.0) and pure MeCD.

The CMA/MeCD complex is represented and indicates an approximate 8 % weight loss

compared to MeCD at time equal to 55 min (T = 250 °C). It is proposed that this weight

loss resulted from dissociation of monomer from the complex. This 8 % weight loss

occurred approximately 35 °C above the boiling point of pure CMA, indicating a

favorable association between monomer and MeCD. This technique has been used in


58

Figure 2.14 Thermogravimetric analysis comparing a CMA/MeCD complex (0.70mol/1.00 mol) and uncomplexed MeCD. Heating procedure was as follows: (1). Heatfrom 25 °C to 120 °C at 10 °C/min (2). Hold from 15 min (3). Heat form 120 °C to 250

°C at 10 °C/min (4). Hold for 15 min (5). Heat from 250 °C to 800 °C at 10 /min.

Figure 2.15 TGA of CMA from 25-150 °C, under N2, at a heating rate of 10 °C/min.

-10

10

30

50

70

90

110

Wei

ght (

%)

20 40 60 80 100 120 140

Temperature (°C) Universal V3.0G TA Instruments


59

Figure 2.16 TGA of MeCD from 25-500 °C, under N2, at a heating rate of 10 °C/min.

Figure 2.17 TGA of CMA/MeCD complex from 25-500 °C, under N2, at a heating rateof 10 °C/min.

-10

10

30

50

70

90

110

Wei

ght (

%)

0 200 400


-10

10

30

50

70

90

110

Wei

ght (

%)

0 50 100 150 200 250 300 350 400 450 500



60

industry as a conformation of complexation between CD and volatile compounds such as

fragrances.57

The monomers and MeCD were also analyzed by TGA. Figures 2.15-17 show

the TGA analysis of CMA, MeCD and the CMA/MeCD complex at a constant heating

rate of 10 °C/min from 25-500 °C. It is interesting to note that at a heating rate of 10

°C/min the wt% of CMA is driven to zero before the temperature reached 135 °C

indicating that when this temperature was reached all of the pure monomer had

volatilized (Figure 2.15). Figure 2.16 shows the TGA analysis of MeCD. There is an

initial drop in wt % as the instrument reaches equilibrium, but then the curve is flat from

60-300 °C. At a temperature of 300 °C degradation occurs. The TGA of the

CMA/MeCD complex shows a similar trend from 60-150 °C (Figure 2.17). After

instrument equilibrium is reached, the curve is flat until the temperature reaches 150 °C.

There is a gradual decline in wt % from 150-300 °C and then a sharp decline due to

degradation of the cyclodextrin. This gradual decline in weight % between 150-300 °C

corresponds to the loss of CMA. It is interesting to note that the loss of CMA does not

occur until 150 °C. Also, the loss is not as rapid as that of pure CMA at this temperature

according to TGA of pure monomer, which indicated that CMA completely evolved by

the time the temperature reached 135 °C at the same heating rate.

Thin layer chromatography (TLC) has also been reported as a method for

confirming complex formation.56,58,59,60,61,62,63,64,65 MeCD and the respective

monomer/cyclodextrin complexes were run under identical conditions and the Rf values

were calculated and compared. Ritter and coworkers58 reported a difference as high as 20

% between the pure cyclodextrin and the complex, however, TLC examination of the

57 Hedges, A. Chem Rev 1998, 98(5), 2035.58 Born, M.; Ritter, H. Macromol. Rapid Commun. 1996, 17, 197.59 Jeromin, J.; Ritter, H. Macromol. Rapid Commun. 1998, 19, 377.60 Jeromin, J.; Ritter, H. Macromolecules 1999, 32(16), 5236.61 Glockner, P.; Ritter, H. Macromol. Rapid Commun. 1999, 20, 602.62 Storsberg, J.; Ritter, H. Macromol. Rapid Commun. 2000, 21, 236.63 Fischer, M.; Ritter, H. Macromol. Rapid Commun. 2000, 21, 142.64 Glockner, P.; Metz, N.; Ritter, H. Macromolecules 2000, 33(11), 4288.65 Casper, P.; Glockner, P.; Ritter, H. Macromolecules 2000, 33(12), 4361.


61

complexes from this study did not give similar results. TLC was done using SiO2 plates

with fluorescent indicator and methanol as eluent. The Rf values of the MeCD and each

of the resulting complexes were found to be identical. This data was somewhat

surprising given the observations reported by Ritter and coworkers. However, qualitative

examination of the TLC data does indicate complex formation between host and guest.

The appearance of a single spot as opposed to a spot for each of the components indicates

complexes of significant strength, because it would not be expected that compounds so

dissimilar in polarity as the monomers and MeCD to elute to the same extent. The

identical Rf values for pure MeCD and the monomer/MeCD complexes indicate that the

properties (i.e. polarity) of the monomers were completely masked during TLC

development.

2.4 Conclusions

Complexation of tBuMA, 2-EHMA, nBuMA, and CMA with MeCD were

successful. With a mixing time of one day, and subsequent solvent removal

carbohydrate/methacrylate complexes were formed with ratios of monomer to MeCD as

high a 0.72 to 1.00. Characterization by NMR, TGA, and TLC was performed, and these

three methods in concert were utilized to support complex formation. All complexes

were found to be water-soluble and are suitable for subsequent aqueous polymerizations.

Phillip H. Madison, IV Chapter III: Methylated-β-Cycodextrin Mediated Aqueous Polymerizations of Hydrophobic Methcrylic Monomers

62

Chapter III is reproduced with permission from Madison, P. H.;Long, T. E. Biomacromolecules 2000, 1(4), 615.

Copyright 2000American Chemical Society


63

Chapter III: Methylated-ββ-Cyclodextrin MediatedAqueous Polymerization of Hydrophobic Methacrylic

Monomers

Abstract

Hydrophobic methacrylic monomers were polymerized in aqueous media using

methylated (1.8)-β-cyclodextrin (MeCD) additives. Hydrophobic monomers t-butyl

methacrylate (tBuMA), cyclohexyl methacrylate (CMA), and 2-ethylhexyl methacrylate

(2EHMA) were each dissolved in chloroform with MeCD. Chloroform was then

evaporated to yield solid monomer/cyclodextrin complexes. Complexes were shown by1H NMR and thermogravimetric analysis (TGA) to have molar ratios of monomer to

MeCD as high as 0.72/1.00. The water-soluble complexes were readily polymerized in

aqueous media using free radical initiation. During polymerization, hydrophobic

methacrylic polymers precipitated and the MeCD remained in solution. Poly(alkyl

methacrylates) synthesized via this method exhibited number average molecular weights

ranging from 50,000 to 150,000 g/mole with polydispersities from 3.2-5.5 depending on

monomer structure. Isolated yields were as high as 86 %. Additionally, corresponding

methacrylic/carbohydrate films were prepared and examined. These blends are

introduced here and are discussed in further detail in Chapter five.


64

3.1 Introduction

The demand for environmentally benign processes is growing as society

becomes increasingly aware of environmental issues involving conventional organic

solvents. The chemical industry is encouraged to look for new means to the same end for

many of its traditional processes that either produce environmentally unfriendly industrial

products or result in toxic by-products.1,2 In an effort to overcome such potential

obstacles with minimal expense, research is directed towards the replacement of

traditional organic solvents with environmentally benign compounds such as carbon

dioxide,3 biomolecules,4 and water. Carbohydrate mediation offers a viable alternative

to organic solvents. Recent efforts have focused on the incorporation of carbohydrates

in polymer backbones5 or in polymer side chains.6,7,8,9,10,11 Cyclodextrins are a family of

cyclic carbohydrates that have received a great deal of attention,12 and are well-known to

solublize hydrophobic compounds in aqueous media.13,14 This attribute has been utilized

in the areas of stereoselective synthesis,15 dual phase catalysis,16 water purification,17,18,19

and rotaxane chemistry.20,21,22

1 Chesnutt, T. Market Response to the Government Regulation of Toxic Substances, The Rand Corp.; SantaMonica, CA, 1998.2 Wagner, I. The Complete Guide to the Hazardous Waste Regulations, 3rd Ed., John Wiley & Sons, Inc.;New York, 1999.3 Shaffer, K.; DeSimone, J. Trends Poly. Sci. 1995, 3, 146-153.4 Mecoy, M. Chem. Eng. News 1999, 77,25-27.5 Aoi, K.; Takasu, A.; Okada, M. Macromolecules 1997, 30, 6134-6138.6 Havard, J.; Vladimorov, N.; Frechet, J.; Macromolecules 1999, 32, 86-94.7 Aoi, K.; Tsutsumichi, K.; Aoki, E.; Okada, M. Macromolecules 1996, 29, 4456-4458.8 Ohno, K.; Tsujii, Y.; Miyamoto, T.; Fukuda, T. Macromolecules 1998, 31,1064-1069.9 Loykalnaunt, S.; Hayashi, M.; Hirao, A. Macromolecules 1998, 31, 9121-9126.10 Renard, E.; Deratan, A.; Volet, G.; Sebille, B. Eur. Polym. J. 1997, 33, 49-57.11 Bachman, F.; Hopken, H.; Kohli, R.; Lohmann, D.; Schneider, J. J. Carbohydrate Chem. 1998, 17, 1359-1375.12 Hedges, A. Chem. Rev. 1998, 98, 2035-2044.13 Bender, M.; Komiyama, M. “Cyclodextrin Chemistry” Springer; Berlin 1978.14 Saenger, W. Angew. Chem. Int. Ed. 1980, 19, 344.15 Shiraishi, Y.; Toshima, N.; Kawarmura, T.; Mihori, H.; Shirai, H.; Hira, H. J. Molecular Catalysis A:Chemical 1999, 139, 149-158.16 Tilloy, S.; Bertoux, F.; Mortreux, A.; Monflier, E. Catalysis Today 1999, 48, 245-253.17 Crini, G.; Bertini, S.; Torri, G.; Naggi, A.; Sforzini, D.; Vechi, C.; Janus, L.; Lekchiri, Y.; Morcellet, M.J. Applied Poly. Sci. 1998, 68, 1973-1978.18 Hattori, K.; Takahaxhi, K.; Inamaru, H.; Imajo, S.; Murai, S. J. Colloid Interface Sci. 1997, 190, 488-490.19 Spencer, J.; He, Q.; Ke, X.; Wu, Z.; Fetter, E. J. Solution Chem. 1998, 27, 1009-1019.20 Born, M.; Ritter, H. Macromol. Rapid. Comm. 1996, 17, 197-202.


65

Ritter et al. have reported the CD mediated aqueous polymerizations of a limited

number of monomers including phenyl and cyclohexyl methacrylates,23 N-methacryloyl-

11-aminoundecanoic acid and N-methacryloyl-1-aminononane,24,25 and isobornyl and n-

butyl acrylates.26 They have also calculated reactivity ratios (r) for the copolymerization

of two complexes,26 and proposed a polymerization mechanism that involves the

dethreading of CD as the radical chain propagates.24 However, preliminary

polymerization studies involving cyclohexyl methacrylate in the presence of MeCD did

not include a discussion of attainable molecular weights or molecular weight

distributions.23 Also, Rimmer and coworkers have examined the emulsion

polymerization of n-butyl methacrylate in the prescence of β-CD, without prior

complexation of monomer and CD.27 However, to date the temperature dependence of

the reaction and a systematic study of the effect of monomer structure on polydispersity

and attainable molecular weights have not been addressed in detail.

This report describes the aqueous polymerization of t-butyl methacrylate,

cyclohexyl methacrylate, and 2-ethylhexyl methacrylate mediated with methylated (1.8)-

β-CD in order to determine the effects of monomer structure, polymerization

temperature, and initiator concentration on the polymerization process, molecular weight,

and molecular weight distribution of the final products. Both tBuMA and 2EHMA are

commercially important acrylic monomers utilized widely in microlithographic

processes, and adhesive applications respectively. The blending of methylated (1.8)-β-

CD with various poly(alkyl methacrylate) homopolymers to form novel, optically clear

carbohydrate/acrylic films will also be described, and the thermal properties of these

films will be presented.

21 Harada, A.; Kawaguchi, Y.; Toshiyuki, N.; Kamachi, M. Macromol. Rapid Comm. 1997, 18, 535-539.22 Okada, M.; Kamuchi, M.; Harada, A. Macromolecules 1999, 32, 7202-7207.23 Jeromin, J.; Ritter, H. Macromol. Rapid Comm.. 1998, 19, 377-379.24 Jeromin, J.; Ritter, H. Macromol. Chem. Phys. 1998, 199, 2641-2645.25 Jeromin, J.; Ritter, H. Macromolecules 1999, 32, 5236-5239.26 Glockner, P.; Ritter, H. Macromol. Rapid Comm. 1999, 20, 602-605.27 Tattersall, P.; Rimmer, S. Polymer 1999, 40, 6673-6677.


66

3.2 Experimental

Purification: All monomers and initiators were purchased from Aldrich and used as

received unless otherwise stated. MeCD was generously donated by Wacker-Chemie and

was used as received. Monomers were vacuum distilled (0.5 mm Hg) from CaH2 using

the freeze-thaw method to degas the monomer and stored at –25 °C under nitrogen.

Complexation: Complexations of tBuMA, 2-EHMA, and CMA were preformed in 200

mL of chloroform with concentrations of approximately 0.04 M of both MeCD and

monomer. Approximately 10.0 g (7.6 mmol) of MeCD and a molar equivalent of

monomer were added to 200 mL of chloroform in a 500 mL erlenmeyer flask. The

solution was stirred for 1-6 days at room temperature. Chloroform was then removed

using a rotoevaporator and the complex was dried in vacuo at 70 °C for 24 hours.

Isolated yields ranged from 90-96 % and ratios of monomer to MeCD ranged from

0.50/1.00 to 0.75/1.00.

Aqueous Homopolymerizations: Homopolymerizations of the complexes were

conducted in a 50 mL 1-necked, round-bottomed, flask with 20.0 mL de-ionized water,

1.00-9.00 weight % (1.36-17.10 mol %) K2S2O8 compared to monomer, and 2.00 g of

complex. The polymerization reactor was then septum capped and sparged with ultra-

pure nitrogen for 5-10 min prior to initiator addition. Polymerization was conducted

under ultra-pure N2 atmosphere (5-8 psi) and allowed to proceed for approximately 24

hours. The precipitated polymer was filtered and dried in vacuo for 18 hrs at 60 °C.

MeCD was recovered by removing the water with a rotoevaporator and drying in vacuo

for 18 hrs at 80 °C.

Bulk Homopolymerizations: 10 mL of either CMA, 2EHMA, or tBuMA was added to a

50 mL 1-necked, round-bottomed, flask with 3.00 mg of BPO dissolved in 1.0 mL of

THF. The polymerization reactor was sealed with a septum and sparged with ultra-pure

nitrogen to eliminate oxygen. The reactor was then heated under nitrogen to 70 °C and

stirred for 24 hours. The product was cooled and THF was stirred over the viscous

polymer. Poly(tBuMA) was subsequently precipitated from THF into 1:1


67

methanol:water (10x compared to polymer solution). Poly(CMA) and poly(2-EHMA)

were precipitated from THF into methanol due to their more non-polar nature.

Methylated (1.8)-ββ-Cyclodextrin/Polymer Blends: Poly(tBuMA)/MeCD, poly(2-

EHMA)/MeCD, and poly(CMA)/MeCD blends were produced by dissolving 1.000 g of

polymer and 0.050-0.200 g of MeCD in 5.0 mL of chloroform. The clear solutions were

then poured into petri dishes and covered. The solvent was allowed to evaporate slowly

and the films were dried in vacuo for 24 hrs at 70 °C.

Characterization: Molecular weights and molecular weight distributions were

determined in NMP/P2O5 (0.02 M) at 60 °C with a Waters Gel Permeation

Chromatograph (GPC) equipped with an external 410 RI detector and Viscotek 150 R

viscometer using a flow rate of 1.0 mL/min. DSC analysis was preformed using a Perkin

Elmer Pyris 1 under N2 atmosphere, from 25 °C to 200 °C at a heating rate of 10 °C/min.

All reported glass transition temperatures (Tg) were based on the second heat profile. All

NMR spectra were obtained in CDCl3 using a Varian 400 MHz NMR.

Thermogravimetric analysis (TGA) was utilized under N2 atmosphere using a Perkin-

Elmer TGA7 and heating cycles varied. TEM analysis was performed on precipitated

product cast from reaction solution onto a carbon grid.


Methacrylic/MeCD complexes were prepared in chloroform solvent (Scheme

3.1). The cyclodextrin utilized in this study was a methylated derivative of beta-

cyclodextrin (1.8 out of 3.0 hydroxyl groups present on each glucose ring were converted

to methoxy groups). Complexation times of six days were used initially as previously

described by Ritter et al,23 however, it became clear that this length of time was not

required due to the observation that complexations of CDs generally tended to reach

rapid equilibrium according to 1H NMR data. It was proposed that complexation

occurred due to increasing concentration as solvent was removed, since it is well known

that the amount of complexation occurring between a host and a guest is dependent upon


68

the concentration of each species in solution.28 Higher concentrations tend to result in

higher degrees of complexation. Consequently, complexation times were reduced to one

day for convenience. Complexation may require only a fraction of this time, but it has

been observed that whether complexation time is one or six days the resulting solid

complex contains the nearly identical ratio of monomer to MeCD (Table 3.1). However,

the exact structure of the complex requires further characterization and will be reported

later.

TGA was utilized to determine the ratio of monomer to MeCD in the resulting

complex from Scheme 3.1. First, TGA of pure, dry MeCD was performed as a reference.

The cyclodextrin/monomer complex was carefully dried to remove any residual solvent

and water and was analyzed under similar conditions. Figure 3.1 illustrates the thermal

stabilities of the CMA/MeCD complex (0.72/1.0) and pure MeCD. The CMA/MeCD

complex is represented and indicates an approximate 8 % weight loss compared to MeCD

at time equal to 55 min (T = 250 °C). It is proposed that this weight loss resulted from

dissociation of monomer from the complex. This 8 % weight loss interestingly occurred

approximately 35 °C above the boiling point of pure CMA, indicating a favorable

association between monomer and MeCD.

The TGA analysis is further supported using 1H NMR spectroscopy (Figure 3.2).

Spectra 1 and 2 represent CMA and MeCD respectively prior to complexation. Spectrum

3 was obtained on the product produced from the complexation process (Scheme 3.1).

Integration of the unsaturated protons (HA and HB) (Figure 3.2) of the monomer and

MeCD (HD) minus contribution of proton (HC) of the CMA monomer was calculated and

a ratio of these were determined. From this data the molar ratio of CMA to MeCD was

calculated and the weight % of CMA was easily determined. In the case of the

CMA/MeCD complex that was shown to undergo an 8 % weight loss at 250 °C by TGA,

the weight % of CMA in the complex was determined to be 8.2 % by 1H NMR

spectroscopy. This correlation demonstrates that TGA is a valuable complimentary

analytical method for facile characterization of alkyl methacrylate/MeCD complexes.

28 Rekharsky, M.; Inoue, Y. Chem. Rev. 1998, 98, 1875-1917.


69

The alkyl methacrylate/MeCD complexes were polymerized in aqueous media

using potassium persulfate as the free radical initiator (Scheme 3.1). It was observed that

methacrylic/carbohydrate complexes were completely soluble in aqueous media.

However, a two phase system was produced in which the monomer and water were

immiscible in the absence of the complexing cyclodextrin. Reaction temperatures,

monomers used, and initiator concentrations were varied and are summarized in Tables

3.2-4. Initially, a relatively large amount of initiator was used (9 weight % to monomer)

because the procedure outlined by Ritter and coworkers was followed. Subsequent

polymerizations utilized 1 weight % initiator to monomer and resulted in higher

molecular weights. A variation in glass transition temperature (Tg) was initially

observed, and glass transitions varied as much as 10 °C compared to the control polymer

produced in bulk. Each monomer was homopolymerized in bulk to obtain high

molecular weight products that were utilized as controls and for subsequent film and

blend production. The glass transition temperatures for reference polymers

poly(tBuMA), poly(2EHMA), and poly(CMA) were 118 °C, -5 °C, and 112 °C,

respectively. Also, 1H NMR showed that varying amounts of MeCD remained

complexed to the polymer (Figure 3.2). Therefore, it was concluded that the amount of

MeCD mixed with the polymer had a significant effect on the Tg. This conclusion was

supported by the preparation and analysis of methacrylic/MeCD films with up to 20

weight % MeCD. Again, the thermal analysis of these films indicated there was a

significant dependence of the MeCD present on the Tg. It is proposed that a low weight

% of MeCD acts as a plasticizer. However, at higher concentrations, approximately 5


70

Scheme 4.1 Preparation of the monomer/MeCD complex (Step 1), and subsequentaqueous polymerization (Step 2).

Figure 3.1 Thermogravimetric analysis comparing a CMA/ MeCD complex (0.70mol/1.00 mol) and uncomplexed MeCD. Heating procedure was as follows: (1). Heat

from 25 °C to 120 °C at 10 °C/min (2). Hold from 15 min (3). Heat form 120 °C to 250°C at 10 °C/min (4). Hold for 15 min (5). Heat from 250 °C to 800 °C at 10 /min.

R' = H or Me

7

CHCl324 hrs

25 oC O

O

RO

O

R

+O

O

OR'R'O

OR'

R = or or

OO

R

OO

O O

R R

K2S2O8

H2O

24 hrs

50 oC

+

Step #1

Step #2

or

O

O

OR'R'O

OR'

7

R' = H or Me


71

Figure 3.2. 1H NMR spectra of CMA, MeCD, CMA/MeCD complex, and poly(CMA) from aqueous polymerization of CMA/MeCDcomplex.


72

Table 3.1 Comparison of results from complexation procedures that involved stirring foreither one or six days in chloroform.

MONOMER NUMBER OF DAYS RATIO MONOMER:MeCDa

tBuMA 6 0.60:1.00

tBuMA 1 0.65:1.00

CMA 6 0.72:1.00

CMA 1 0.70:1.00

a- ratios determined using Varian 400 MHz 1H NMR in CDCl3. Calculated from the resonances of the twoprotons of the monomer at approximately 5.5 and 6.1 ppm were compared to the MeCD proton at 5.0 ppm.

weight %, the presence of MeCD caused an increase in Tg (Tables 3.5-6). It was

observed that the glass transition temperatures of polymers prepared by MeCD mediated

aqueous polymerizations varied as much as 21 °C depending on the amount of MeCD

present. Gel permeation chromatography indicated that the residual cyclodextrin was not

covalently bonded to the polymer backbone. In addition, redissolution of the polymer

products containing 3-8 mole percent in tetrahydrofuran and subsequent precipitation into

water quantitatively removed the residual cyclodextrin. 1H NMR analysis indicated the

absence of resonances associated with residual cyclodextrin. Moreover, a direct

correlation between the monomer utilized for polymerization and the amount of residual

MeCD in the precipitated polymer was not observed.

The results of the aqueous polymerizations of the monomer/MeCD complexes are

summarized in Tables 3.2-4. Conditions A and B are examples of aqueous radical

polymerizations of the specified complex. A was initiated with 1.0 weight % K2S2O8 to

monomer while B was initiated with 9.0 weight % K2S2O8 to monomer. As expected, a

comparison of A to B at the same temperature shows that molecular weights can be

controlled by variations in initiator concentrations alone. Comparison of two As at

different temperatures indicated that an increase in reaction temperature resulted in lower


73

molecular weights. This is attributed simply to the fact that the half life of K2S2O8 is

estimated to be approximately 1 order of magnitude less at 60 °C than it is at 50 °C,29

hence there is a higher concentration of radicals during polymerization. It is also

encouraging that all polymerizations tend to exhibit similar molecular weight trends

depending on initiator concentration and polymerization temperature, and that these

trends are typical for traditional free radical polymerizations. For example, under

condition A at 50 °C both poly(CMA) and poly(tBuMA) exhibit number average

molecular weights of 142,000 and 137,000 g/mole respectively, and increases in either

temperature or initiator concentration resulted in the expected decrease in number

average molecular weight. 1H NMR analyses of polymer products indicated that the

cyclodextrin mediated aqueous polymerizations resulted in poly(alkyl methacrylate)s

with stereochemistry similar to that obtained in conventional bulk polymerizations. For

example, poly(tBuMA) produced from conventional bulk polymerization gave a 53 %

syndiotactic, 38 % heterotactic, and 9 % isotactic product, and poly(tBuMA) produced

from MeCD mediated aqueous polymerization resulted in a product that was 55 %

syndiotactic, 40 % heterotactic, and 5 % isotactic. Isolated yields were typically as high

as 85 % in water with 80-95 % recovery of MeCD in all cases. 1H NMR analysis of

recovered MeCD indicated that there was no change in the chemical composition, and

therefore could be used repeatedly without purification. Experiments using recycled

MeCD resulted in identical results. Transmission electron microscopy (TEM) was also

employed to investigate the precipitant formed during aqueous polymerizations. A

representative sample of reaction mixture was syringed out of the reactor and a single

drop was placed on a carbon grid. The water was then allowed to evaporate leaving the

solid polymer precipitate on the carbon grid. Figure 3.3 shows typical TEM photographs

obtained at different magnifications of the precipitate obtained from the aqueous

polymerization of the tBuMA/MeCD complex

Another interesting trend in the data is the polydispersity indices (PDI) of

different polymers. The trend in molecular weights under the different conditions was

similar for each polymer, but when comparing one polymer to another the

29 Kolthoft, I.; Miller, I. J. Am. Chem. Soc. 1951, 73, 3055.


74

Table 3.2 Polymerizations of t-butyl methacrylate under specified conditions.

Polymer ConditionsTemperature

(°°C)Mn

a

(g/mol)Mw

Mn

Tgb

(°°C)% Yieldc

poly(tBuMA)1

poly(tBuMA)2

poly(tBuMA)3

A

B

A

50

50

60

137,000

90,000

48,000

3.45

3.69

3.62

107

120

125

77

85

65

Table 3.3 Polymerizations of cyclohexyl methacrylate under specified conditions.


(°°C)Mn

a

(g/mol)Mw

Mn

Tgb

(°°C)% Yieldc

poly(CMA)1

poly(CMA)2

poly(CMA)3

A

B

A

50

50

60

142,000

93,000

69,000

5.91

4.39

6.24

107

110

105

50

75

72

Table 3.4 Polymerizations of 2-ethylhexyl methacrylate under specified conditions.


(°°C)Mn

a

(g/mol)Mw

Mn

Tgb

(°°C)% Yieldc

poly(2EHMA)1

poly(2EHMA) 2

poly(2EHMA )3

A

B

A

50

50

60

140,000

56,000

53,000

3.56

3.20

2.75

2

5

-8

74

80

86

a- Waters GPC with external 410 RI detector and Viscotek 150R viscometer, NMP/P2O5 (0.02 M)solvent @ 60 oC and 1.0 mL/min flow rate

b- Pyris 1 DSC (2nd heat @ 10 °C/min), N2c- Determined gravimetrically from precipitated product. Mass contribution of MeCD was

determined by Varian, 400 MHz, 1H NMR in CDCl3

Conditions:A-Polymerization from the complex in water initiated with 1.0 weight% K2S2O8

B-Polymerization from the complex in water initiated with 9.0 weight% K2S2O8


75

.

Tables 3.5-6 Dependence of Tg on weight % MeCD present in film. Approximately 1mm thick films were optically clear as cast from CHCl3 with up to 20 weight % MeCD.

a - Pyris 1 DSC (2nd heat @ 10 °C/min), N2

polydispersities show a significant trend. The mean PDI increased 13 % going from

poly(2EHMA) (3.17 ± 0.41) to poly(tBuMA) (3.59 ± 0.12), and increased even more (53

%) from poly(tBuMA) to poly(CMA) (5.51 ± 0.98). It is anticipated that PDI variations

are due to the nature of the interactions between the polymer and MeCD as chain

propagation occurs. Ritter et al proposed a mechanism involving the dethreading of CD

during propagation of the radical chain.19 It is believed that the affinity of the monomers

to MeCD is driven primarily by the hydrophobic-hydrophobic interaction between the

monomer and the MeCD cavity.30 Therefore, a compound that fits snugly into the cavity

will tend to have a stronger force of attraction.

Corey-Pauling-Koltun (CPK) space filling atomic models were employed to

investigate the relationship between monomer structure and PDI results obtained. CPK

models are well known atomic models that are utilized to examine the special

relationships of molecules.31 CPK models of the t-butyl group (Figure 3.4) indicated that

it formed the tightest fit, having the greatest circumference occupied by hydrophobic

groups, and is suspected to have a large affinity for the MeCD cavity. CPK models of the

2-ethylhexyl ester alkyl indicated that it too has a large circumference of space occupied

by hydrophobic groups and would have a large affinity towards the cavity of MeCD. The

30 Amiel, C.; Sebille, B. Adv. Colloid Interface Sci. 1999, 79, 105-122.

Weight % MeCD Tga (ºC)

0 118

5 105

10 117

20 124

Poly(t-butyl methacrylate) Poly(cyclohexyl methacrylate)


0 112

5 100

10 105

20 110


76

Figure 3.3 TEM analysis of precipitate formed from the aqueous polymerization of atBuMA/MeCD complex; performed on precipitated product cast from reaction solution

onto a carbon grid.

Figure 3.4 CPK molecular model of a possible tBuMA/β-CD complex. 31 Cram, J.; Cram, D. Science 1974, 185, 4127.


77

2-ethylhexyl group however also has substantial length, which is believed to contribute to

its affinity towards MeCD. In addition, the CPK model of the cyclohexyl ester alkyl was

shown to occupy the MeCD cavity less efficiently than either of the previous two, and

has less affinity towards the MeCD cavity. The space filling models of the alkyl groups

combined with the resulting PDI data suggest that there was a direct correlation between

the size of the alkyl chain and the resulting PDI obtained. The mechanism involved in

the dethreading of MeCD during chain propagation affects the solubility properties of the

polymer. Furthermore, because the polymer precipitates out of solution as it is formed, it

is logical to conclude that variations in solubility will result in loss of control during

polymerization, which was observed in the molecular weight distributions. Based on

polymerization results and CPK space-filling models, it is proposed that the t-butyl and 2-

ethylhexyl alkyl substituients are preferred for β-cyclodextrin mediation in aqueous

media.

Preliminary examination of a fourth monomer, n-butyl methacrylate further

supported this conclusion. The space-filling model indicated that it would have the least

affinity towards the MeCD cavity compared to all other monomers. Therefore, the

resulting polymer would be expected to exhibit an increase in PDI when compared to the

previous three polymers. The mean PDI of poly(n-butyl methacrylate) was found to be

10.40 ± 0.74, which is greater than all polymers previously discussed.

3.4 Conclusions

It has been demonstrated that with complexation times of one day, solid

complexes of tBuMA, CMA, or 2-EHMA with MeCD were obtained. Molar ratios of

monomer to MeCD as high as 0.72/1.00 were observed in the resulting solids. Data

obtained from the novel characterization of these complexes using TGA correlated well

with results obtained using 1H NMR spectroscopy. Polymers were exhibited number

average molecular weights as high as 140,000 g/mol with PDI’s as low as 3.2.

Hydrophobic, high molecular weight acrylic polymers were prepared in water with

acceptable polydispersities and isolated yields as high as 86 %. Additionally, 80-95 % of

the MeCD used in these reactions was recovered and 1H NMR data and subsequent


78

polymerizations indicated that the carbohydrate could be recycled. Novel miscible

methacrylic/carbohydrate films were also produced and shown to possess interesting

thermal properties.

Phillip H. Madison, IV Chapter IV: Emulsion Polymerizations Using MeCD and Linear Dextrin as Emulsifiers

79

CHAPTER IV: Emulsion Polymerizations UsingCyclodextrin and Linear Dextrin as Emulsifiers

Abstract

Methylated(1.8)-β-cyclodextrin (MeCD) and linear dextrin were utilized as

emulsifiers in emulsion polymerization of 2-ethylhexyl methacrylate (2EHMA) with

varied results. It was found that linear dextrin at concentrations of 3.0 wt% produced a

stable latex product with a number average molecular weight of 255,000 and an isolated

yield of >90%. MeCD on the other hand failed to produce a stable emulsion at

concentrations between 0.9-3.0 wt%, but at 3.0 wt% gave high number average molecular

weight (474,000) polymer with a yield of >90%. There is no known literature precedence

in which 2EHMA has been shown to facilitate an emulsifier free emulsion

polymerization. Therefore, it is apparent that an unconventional heterogeneous

mechanism is taking place in the MeCD containing systems. It is proposed that MeCD

acts as a phase transfer catalyst rather than a surfactant for 2-ethylhexyl methacylate

monomer, thus facilitating a dispersion rather than an emulsion type polymerization

mechanism. Further investigation is required in order to further elucidate this

mechanism.


80

4.1.1 Introduction

Emulsion polymerization is used extensively industrially to make polymers with

applications where a latex system is viable such as in the areas of adhesives and

paints.1,2,3,4 There are several major advantages of the emulsion polymerization process

over conventional bulk polymerization.5,6 The first is that control of temperature is

simple. In emulsion polymerization, the growing polymer is evenly dispersed in a

continuous phase, which is usually water. In this type of system the continuous phase

acts as a heat sink and the temperature can easily be controlled allowing for the entire

system to remain at a constant temperature throughout the reaction. In typical bulk

systems, local temperature fluctuations can occur as a result of inefficient heat dissipation

as agitation becomes more difficult due to viscosity increases at high molecular weights.

These local temperature fluctuations result in a nonuniform polymer and in some cases

degradation can occur.6

The second advantage of emulsion polymerization is the form to the resulting

product. Handling of a latex is easier than a bulk polymer and for a number of

applications the latex that is formed can be used directly eliminating any further isolation

procedures. Another advantage of emulsion polymerization is the ability to achieve high

molecular weight polymer at high rates. Generally, in order to achieve high molecular

weight in conventional polymerizations rate and/or yield must be compromised.

A simple emulsion recipe generally involves four components. The first

component is the continuous phase. This is the component in which the monomer is

dispersed, and is typically water. The second component is the monomer. Generally any

liquid monomer at reaction temperature that is insoluble in the continuous phase is

acceptable. The initiator is the third component and must be a free radical initiator that is

1 Feeney, P.; Napper, D.; Gilbert, R. Macromolecules 1984, 17(12), 2520.2 Vanderhoff, J. J. Polym. Sci.: Polym. Symp. 1985, 72, 161.3 Gol’dfein, M.; Kozhevnikov, N.; Trubnikov, A. Polym. Yearb. 1985, 12, 89.4 Poehlein, G. ACS Symp. Ser. 1985, 285, 131.5 Gilbert, R. Emulsion Polymerization: A Mechanistic Approach Academic Press, 1995.6 Odian, G. Principles of Polymerization John Wiley & Sons, Inc., NY 1991.


81

soluble in the continuous phase. This means that most initiators used in emulsion

polymerizations are water-soluble free radical initiators. The last component of an

emulsion polymerization is the surfactant, or surface-active agent. This component is

crucial to stabilizing the latex. The most common types of surfactants used industrially

today are ionic surfactants. The most widely used surfactants including sodium lauryl

sulfate, sodium dodecylbenzene sulfonate, potassium stearate, and potassium palmitate

all have similar structural features in that they consist of both hydrophilic and

hydrophobic portions.

In this section the use of linear dextrin and methylated(1.8)-β-cyclodextrin

(MeCD) as surfactants in emulsion polymerizations of 2-ethylhexyl methacrylate will be

discussed. The linear dextrin utilized is made up of a linear sequence of glucose rings.

By gel permeation chromatography (GPC) each molecule was found to contain an

average of five repeat units. MeCD is a cyclic form of glucose in which 1.8 out of 3 of

the hydroxyl groups present on each glucose ring have been methoxy substituted and

where six of these substituted glucose rings are connected to form a truncated cone type

structure. Liner dextrin and MeCD do not posses the typical surfactant structure

consisting of both a hydrophilic head and a hydrophobic tail, therefore they are not

expected to effectively stabilize the latex. These experiments have been undertaken

mainly in an attempt to gain understanding into the mechanism involved in the aqueous

polymerizations mediated by MeCD.

4.2 Experimental

Purification: All monomers were purchased from Aldrich and vacuum distilled (0.5 mm

Hg) from CaH2 using the freeze-thaw method to degas the monomer and stored at –25 °C

under nitrogen. MeCD was generously donated by Wacker-Chemie and was used as

received. Linear dextrin was purchased from Aldrich and found to have an average

degree of polymerization of approximately five by gel permeation chromatography.

Benzoyl peroxide (BPO) initiator was purchased from Aldrich and used as received.


82

Emulsion polymerization of 2-ethylhexyl methacrylate: 10 g (11.3 mL) of 2-

ethylhexyl methacrylate (2EHMA) was added to a 50 mL 1-necked, round-bottomed

flask with 27.5 mL of water and 25 mg of potassium persulfate. The system was then

sparged with ultrapure nitrogen. Then either 0.25 or 0.83 g of MeCD or linear dextrin

was subsequently charged in the flask and a septum was wired on to seal the system. The

reactor was then heated to 60 °C under nitrogen and stirred for either 4 or 24 h. The

product was then isolated by removal of the bulk of the liquid by use of a rotoevaporator.

The solid was then dried in vacuo for 24 h.


determined in NMP/P2O5 (0.02 M) at 60 °C with a Waters gel permeation chromatograph

(GPC) equipped with an external 410 RI detector and Viscotek 150 R viscometer using a

flow rate of 1.0 mL/min. DSC analysis was preformed using a Perkin Elmer Pyris 1

under N2 atmosphere, from -50 °C to 200 °C at a heating rate of 10 °C/min. All reported

glass transition temperatures (Tg) were based on the second heat profile. All NMR

spectra were obtained in CDCl3 using a Varian 400 MHz NMR.


Methylated(1.8)-β-cyclodextrin and linear dextrin were utilized as surfactants in

emulsion polymerizations of 2-ethylhexyl methacrylate. Ionic surfactants including fatty

acid soaps, sulfates and sulfonates are most commonly used because they generally form

stable emulsions. In some cases, nonionic compounds such as poly(ethylene oxide),

poly(vinyl alcohol), or cellulose derivatives are used with anionic species to fine tune the

resulting latex. Figure 4.1 shows the chemical structures of several of the more common

ionic emulsifiers, as well as the structures of MeCD and dextrin. It should be noted that

by simple comparison of chemical structure one would not expect either dextrin or

MeCD to be effective emulsifiers. They do not contain the typical structure of

emulsifiers, which consists of a hydrophilic head, the ionic group and a long hydrophobic

tail. This structure consisting of both hydrophobic and hydrophilic ends is believed to be


83

a - Waters GPC with external 410 RI detector and Viscotek 150R viscometer, NMP/P2O5 (0.02 M)

solvent @ 60 °C and 1.0 mL/min flow rate

Figure 4.1 Chemical structures of several of the more common ionic emulsifiers, and thestructures of MeCD and linear dextrin.

Na

O

S

O

O

O

NaS

O

O

O

KO

O

KO

O

Common Ionic Surfactants:

Sodium lauryl sulfate

Sodium dodecylbenzene sulfonate

Potassium stearate

Potassium palmitate

Compounds Utilized as Surfactants in This Study:

OO

OR'R'O

OR'

7

R' = H or Me

OOHO

OHHO

OH

H

n

Methylated(1.8)-beta-Cyclodextrin Linear Dextrin

n = 5 by GPCa


84

essential for the development of stable micelle structures. The formation of stable

micelles is crucial because within them is where the locus of polymerization occurs in

emulsions polymerization.6

In an effort to determine the type of polymerization that occurs through the

cyclodextrin mediated polymerizations in water and ethylene glycol, MeCD and linear

dextrin were incorporated into aqueous polymerizations of 2-EHMA in typical emulsifier

quantities. The recipes followed for these reactions in terms of parts by weight are

included in Table 4.1. In all cases water, surfactant, and initiator were kept constant at

100, 36, and 0.1 parts by weight respectively in order to examine the effect of different

emulsifier concentrations. Typical amounts of ionic and nonionic emulsifiers used

compared to water content are 0.2-3.0 and 2.0-10 wt % respectively.6 In this study

weight percents of dextrin and MeCD were varied from 0.9-3.0 wt% compared to water

content.

Table 4.1 Recipe for emulsion polymerizations using methylated-β-cyclodextrin or lineardextrin as surfactants.

Compound Parts by weight

H2O 100

Monomer 36

Emulsifier 0.9-3.0

Initiator 0.1

Reaction was carried out at 60 °C under nitrogenatmosphere. Time of reaction was varied from 4-24 h.


85

First a concentration of 0.9 wt% to water, which is typical for ionic emulsifiers,

was used for both MeCD and dextrin. The reactions were allowed to run for four hours

which is generally a long enough time for emulsion polymerization given that one of their

major advantages is that they are generally able to achieve high molecular weight at high

rates. The polymerization incorporating linear dextrin resulted in only 24 % isolated

yield, but gave extremely high number average molecular weight material (>1,400,000),

which was close to the exclusion limit of the GPC. In the polymerization in which

MeCD was utilized as the emulsifier, an isolated yield of 13 % was obtained, and resulted

in a 163,000 number average molecular weight polymer. In both cases, however, a stable

latex was never observed. As one would expect for a stable latex, when the reaction

mixtures were stirred they appeared milky. However, when stirring was stopped, the

latex separated to two-layers, which suggests an unstable emulsion.

The concentrations of MeCD and dextrin were subsequently increased to 3.0 wt%

to water and the reaction time was increased to one day. In both cases again, at the onset,

when the mixtures were stirred they appeared milky, but separated into two layers in the

absence of agitation. After the 24 h period, the dextrin emulsion still remained milky,

and when agitation was stopped the solution remained milky. The liquid was removed

first by use of a rotoevaporator and then subsequent drying under vacuum. Accounting

for the weights of both initiator and dextrin the isolated yield of polymer was >90 %.

GPC indicated that the polymer had a number average molecular weight of 255,000.

This is substantially lower than the molecular weight of the polymer in which only 0.9

wt% dextrin was used. However, it has been well established that for emulsion

polymerizations increasing the concentration of surfactant results in a larger number of

micelles, which in turn leads to a reduction in molecular weight obtained.5,6 These data

and observations for the polymerizations utilizing linear dextrin as emulsifier are

indicative of an emulsion type mechanism (Table 4.2). In further studies, scanning

electron microscopy (SEM) will be used to obtain the particle size distribution of the

resulting latex.


86

Table 4.2 Results from emulsion type polymerizations incorporating MeCD and lineardextrin in emulsifier concentrations.


solvent @ 60 °C and 1.0 mL/min flow rateb - Determined gravimetrically after evaporation of solvent and monomers and subtraction of additional,

nonvolatile reaction components

Monomer Emulsifierwt% Emulsifier

compared to H2O(to monomer)

Mna Isolated

Yieldb

2-ethylhexylmethacrylate

Dextrin0.9

(2.4)>1400 K 24%


Dextrin3.0

(8.0)255,000 >90%


Cyclodextrin0.9

(2.4)163,000 13%


Cyclodextrin3.0

(8.0)474,000 >90%


87

An odd behavior was observed after approximately 6 h for the reaction

incorporating MeCD. A two-phase system had been formed, however in this case the

solid polymer rather than a monomer layer was collected above the aqueous layer when

agitation stopped. The polymer was removed and dried and the isolated yield was

observed to be greater than 90 %. The molecular weight was also found by GPC to be

474,000. It is clear from these observations that MeCD does not facilitate a conventional

emulsion polymerization of 2EHMA. In fact these observations do not support any of the

four major heterogeneous polymerization mechanisms outlined by Arshady.7 When

analyzing the four factors defining the different types of heterogeneous polymerizations it

was found that this polymerization did not fit any of the definitions of conventional

suspension, dispersion, precipitation, or emulsion polymerization. Therefore, an

alternate, nonconventional polymerization mechanism must be taking place. Given that

cyclodextrins are well known to facilitate the phase transfer of small molecules through

complexation, it is proposed that in the case of the emulsion type polymerizations with

CD in emulsifier concentrations a dispersion type mechanism may be occurring.

In dispersion polymerization the components start out homogeneous.7 Initiation

occurs in the media and polymer chains begin to grow. Depending on the solvency of the

media the polymer particles then phase separate forming primary particles. These

particles are then swollen with monomer and/or solvent and thus the polymerization then

proceeds mainly within these particles. 2-ethylhexyl methacrylate is insoluble in water

and thus would not undergo a typical dispersion polymerization. However, through

complexation with cyclodextrin the monomer can be dissolved in water, initiated with

potassium persulfate, and chain propagate to a critical size when it then precipitates from

solution. Poly(2-ethylhexyl methacrylate) has been shown to have appreciable solubility

in its monomer according to the bulk polymerizations performed. Therefore, it is

proposed that once the polymer precipitates it is swollen by the monomer and the bulk of

polymerization can thus take place in these swollen particles. These particles are,

however, not stabilized by the remaining cyclodextrin so gross coagulation occurs. This

7 Arshady, R. Colloid Polym. Sci. 270(8) 1992 717.


88

theory is tentative at this time and further studies are necessary to elucidate the actual

mechanism. However, this mechanism is consistent with the observations, and could

account for the high conversion and molecular weights achieved.

4.4 Conclusions

At a concentration of 3.0 wt% to water, linear dextrin appeared to produce a

stable latex in the polymerization of 2-ethylhexyl methacrylate. Isolated yield of polymer

was >90 % with a number average molecular weight of 255,000. At a concentration of

0.9 wt% to water, however, low yields of poly(2-ethylhexyl methacrylate) were obtained

and a stable latex was not observed. MeCD on the other hand failed to produce a stable

latex of poly(2-ethylhexyl methacrylate) at concentrations of 0.9 or 3.0 wt% MeCD to

water. However, a high molecular weight coagulated polymer was produced with >90 %

yield at a MeCD concentration of 3.0 wt% to water. It is apparent that an unconventional

mechanism is taking place in the MeCD systems. It is proposed that MeCD acts as a

phase transfer catalyst rather than a surfactant for 2-ethylhexyl methacylate monomer,

thus facilitating a dispersion rather than an emulsion type polymerization mechanism.

Further investigation is required in order to further elucidate this mechanism.

Phillip H. Madison, IV Chapter V: The Preparation and Characterization ofCarbohydrate/Methacrylic Blends

89

Chapter V: The Preparation and Characterization ofCarbohydrate/Methacrylic Blends

Abstract

This chapter discusses the benzoyl peroxide initiated, bulk polymerizations of t-

butyl methacrylate (tBuMA), cyclohexyl methacrylate (CMA), and 2-ethylhexyl

methacrylate (2EHMA) and their subsequent use in the preparation of

carbohydrate/methacrylic films. The bulk polymers were utilized as references for

physical properties for the polymers produced through polymerization of the

MeCD/monomer complexes in either aqueous solution or in ethylene glycol, and were

also used in the preparation of carbohydrate/methacrylic films incorporating 5-50 wt%

MeCD. Films with up to 20 wt% MeCD were optically clear as cast from chloroform

and exhibited interesting thermal properties. These properties were investigated and are

discussed here.


90

5.1 Introduction

Blends of natural polymers with synthetic polymers have gained much attention

in recent years. As society is becoming more sensitive to the potential adverse effects of

non-biodegradable polymers, biodegradable films and blends are gaining increased

interest. The incorporation of a biodegradable component into polymer systems has been

shown to greatly decrease the biodegradation time of these materials.1,2,,3,4,5,6,7,8,9,10 In

many cases natural components such as carbohydrates and starches have been utilized,

and were shown to be effective. For example, blends of low density polyethylene with

starch, lignin and dextrin, and wood flour have all shown to degrade substantially faster

than pure low density polyethylene.11 Substantial work has also been involved with the

development and characterization of biodegradable homopolymers.12 For example,

polycaprolactone, poly(butylenes succinate), and poly(butylenes adipate) have been

studied and found to undergo significant biodegradation. Poly(lactic acids)13,14 and

poly(hydroxy butyrates)15,16 are also two common polymers that have been studied for

biodegradable applications.

Natural-synthetic blends have also been made of cyclodextrins and different

polymers for the purpose of drug delivery. In fact Uekama, Hirayama, and Irie17 have

recently published a review dealing with cyclodextrin drug carrier systems. Work has

1 Park, S.; Lim, S.; Shin, T.; Choi, H.; Jhon, M. Polymer 2001, 42(13), 5737.2 Park, J.; Im, S.; Kim, S.; Kim, Y. Polym. Eng. Sci. 2000, 40(12).3 Canale, P.; Mehta, S.; McCarthy, S. Annu. Tech. Conf. – Soc. Plast. Eng. 2000, 58(3), 2680.4 Meredith, J.; Amis, E. Macromol. Chem. Phys. 2000, 201(6), 733.5 McCarthy, S.; Ranganthan, A.; Ma, W. Macromol. Symp. 1999, 144, 63.6 Cyras, V.; Fernandez, N.; Vazquez, A. Polym. Int. 1999, 48(8), 705.7 Arvanitoyannis, I. J. Mcromol. Sci., Rev. Macromol. Chem. Phys. 1999, C39(2), 205.8 Griffin, G. Polym. Degrad. Stab. 1994, 45(2), 241.9 Chiellini, E.; Cinelli, P.; Corti, A.; Kenawy, E.; Fernandes, E.; Solaro, R. Macromol. Symp. 2000, 152, 83.10 Fernando, R.; Glass, J. Polym. Mater. Sci. Eng. 1984, 51, 461.11 Tudorachi, N.; Cascaval, C.; Rusu, M. J. Polym. Eng. 2000, 20(4), 287.12 Komarek, A.; Uhlrich, J.; Sherlock, P.; Ibeh, C. Annu. Tech. Conf. – Soc. Plast. Eng. 2000, 58(3), 272.13 Kimur, H.; Ogura, Y. Ophthalmologica 2001, 215(3), 143.14 Martin, O.; Averous, L. Polymer 2001, 42(14), 6209.15 Van der Walle, G. A. M.; De Koning, G. J. M.; Weusthuis, R. A.; Eggink, G. Adv. Biochem.Eng./Biotechnol. 2001, 71, 263.16 Kasuya, D.; Mitomo, H.; Nakahara, M.; Akiba, A.; Kudo, T.; Doi, Y. Biomacromolecules 2000, 1(2),194.17 Uekama, K.; Hirayama, F.; Irie, T. Chem. Rev. 1998, 98(5), 2045.


91

also been persued in which cyclodextrin is chemically grafted to a polymeric backbone.18

In these systems the pendent cyclodextrin groups were used to complex drug molecules.

These cyclodextrn/polymer systems were shown to be comparable to other methods of

drug delivery, including those that utilize polyethylenimine or lipofectamine.

Cyclodextrins have also been incorporated into carrier systems to increase the water

solubility and/or bioavailability of several types of drug compounds.19,20

The cyclodextrin mediated aqueous polymerizations of hydrophobic

methacrylates have been the subject of a previous work. From these reactions it was

found that there was residual free cyclodextrin remaining in the polymer product. It was

also discovered that the glass transitions of the products obtained were not reproducible

from one batch to the next and appeared to depend on the concentration of residual

cyclodextrin remaining in the polymer. This section describes the bulk polymerizations

of the methacrylates that were also utilized in the aqueous polymerizations mediated by

methylated(1.8)-β-cyclodextrin (MeCD) for the purpose of references for physical

properties. These polymethacrylates from the bulk reactions were also used in the

formation of carbohydrate/methacrylic films in order to elucidate the effects of

concentration of MeCD on the thermal properties of the films.

5.2 Experimental

Purification: All monomers were purchased from Aldrich and vacuum distilled (0.5 mm

Hg) from CaH2 using the freeze-thaw method to degas the monomer and stored at –25 °C

under nitrogen. MeCD was generously donated by Wacker-Chemie and was used as

received. Benzoyl peroxide (BPO) initiator was purchased from Aldrich and used as

received.

Bulk Homopolymerizations: 10 mL of either CMA, 2EHMA, or tBuMA was added to a

50 mL 1-necked, round-bottomed, flask with 3.00 mg of BPO dissolved in 1.0 mL of

18 Gonzalez, H.; Hwang, S.; Davis, M. Bioconjugate Chem. 1999, 10(6), 1068.19 Duchene, D.; Wouessidjewe, D.; Ponchel, G. Journal of Controlled Release 1999, 62, 263.20 Wulff, M.; Alden, M. European Journal of Pharmaceutical Sciences 1999, 8, 269.


92

THF. The polymerization reactor was sealed with a septum and sparged with ultra-pure

nitrogen to eliminate oxygen. The reactor was then heated under nitrogen to 70 °C and

stirred for 24 hours. The product was cooled and THF was stirred over the viscous

polymer. Poly(tBuMA) was subsequently precipitated from THF into 1:1

methanol:water (10x compared to polymer solution). Poly(CMA) and poly(2-EHMA)

were precipitated from THF into methanol due to their more non-polar nature.

Methylated (1.8)-ββ-Cyclodextrin/Polymer Blends: Poly(tBuMA)/MeCD, poly(2-

EHMA)/MeCD, and poly(CMA)/MeCD blends were produced by dissolving 1.000 g of

polymer and 0.050-0.500 g of MeCD in 5.0 mL of chloroform. The clear solutions were

then poured into petri dishes and covered with a crystallization dish propped up on one

side approximately 1mm. The solvent was allowed to evaporate slowly for three days

and the films were dried in vacuo for 24 hrs at 70 °C.





Elmer Pyris 1 under N2 atmosphere, from -50 °C to 200 °C at a heating rate of 10 °C/min.




Homopolymers of 2EHMA, tBuMA, and CMA were synthesized in the bulk

(Scheme 5.1). GPC analysis indicated extremely high number average molecular weights

(>1,000,000) for poly(tBuMA) and poly(CMA), with weight average molecular weights

above the exclusion limit for the column utilized. The number average molecular weight

of poly(2EHMA) was found to be substantially lower, approximately 250,000. This

lower molecular weight can be attributed to the relatively high radical chain transfer

constant associated with the 2-ethylhexyl group of the monomer. For example, 2-


93

ethylhexyl acrylate shows a chain transfer constant of 6.28 x10-4 compared to that of

methyl acrylate, which has a value of 0.1 x10-4 under similar conditions.21

These homopolymers synthesized from the bulk were subsequently utilized as

references of physical properties for those polymer synthesized through cyclodextrin

mediation in water and ethylene glycol. These bulk homopolymers were also utilized in

the preparation of carbohydrate/methacrylic blends incorporating up to 50 wt% MeCD,

which were found to possess interesting thermal properties.

Approximately 1 mm thick films of poly(2EHMA), poly(tBuMA), and

poly(CMA) were produced. 1.00 gram of polymer was mixed with 5.0 mL of

chloroform, covered and stirred overnight to completely dissolve the polymer. The

chloroform solution was then poured into a petri dish. The petri dish was covered with a

crystallization dish and propped up on one side approximately 1 mm to allow for slow

evaporation of the solvent. The solutions were left to stand undisturbed for three days to

allow for evaporation of the majority of the solvent. The films were then dried invacuo

overnight at 70 °C, removed, and stored in a desiccator. The glass transition

temperatures were then measured using DSC and were found to be consistent with those

found for the bulk polymers prior to film formation.

All films were optically clear. This method produced highly flexible, creasable

films of poly(2EHMA), however, the films produced form poly(tBuMA) and

poly(CMA) were found to be noncreasable and brittle. These three polymers were used

to produce carbohydrate/methacrylic blends incorporating 5-50 wt% MeCD. Blends

were prepared in a manner identical to the films previously described by dissolving 1.00

g each of poly(2EHMA), poly(tBuMA), and poly(CMA) and 5, 10, 20, 30 and 50 wt%

MeCD in chloroform and following the procedure described previously. In all cases

those blends containing up to 20 wt% MeCD produced films that were optically clear.

21 Brandrup, J.; Immergut, E.; Grulke, E. (eds.) Polymer Handbook, 4th edition John Wiley & Sons; NewYork; 1999.


94

Scheme 5.1 Bulk polymerizations of tBuMA, CMA, and 2EHMA.

Tables 5.3-4 Dependence of Tg on weight % MeCD present in film. Approximately 1mm thick films were optically clear as cast from CHCl3 with up to 20 weight % MeCD.

a - Pyris 1 DSC (2nd heat @ 10 °C/min), N2


0 118

5 105

10 117

20 124

Poly(t-butyl methacrylate) Poly(cyclohexyl methacrylate)


0 112

5 100

10 105

20 110

R = or or

OO

R

O

O

R24 h, 70 oC

BPO, Bulk


95

Those blends, however, with wt% of MeCD higher than 20 % produced hazy films that

were extremely brittle.

The clear films were analyzed by DSC and the wt% MeCD and resulting Tg’s for

the poly(tBuMA) and poly(CMA) films are reported in Tables 5.3-4. The blends

produced from poly(2EHMA) however had extremely broad glass transitions as

determined by DSC at a heating rate of 10 °C/min. The heating rate was subsequently

decreased to 5 °C/min resulting in very little or no narrowing of the region.

Consequently, calculation of the glass transition temperatures (Tg) for these systems were

unattainable. However, the series of Tg’s observed from the carbohydrate/methacrylic

blends incorporating poly(tBuMA) and poly(CMA) show interesting trends.

Plasticization is a phenomenon that occurs in polymers when two or more

components are blended together. Plasticization involves a reduction of the glass-to-

rubber transition temperature. It is well known that small molecules can be used to

plasticizer polymeric materials. There have been a number of studies on the effect of

structure and amount of different plasticizers published in recent literature.22,23

Plasticizers work to reduce the Tg of a polymer by contributing a large amount of free

volume, which promote cooperative segmental motion at lower temperatures.24,25

It appears that in both cases small amounts of MeCD act to plasticize the polymer

and thus decrease the Tg as much as 10 °C. However, at some critical concentration of

MeCD the Tg begins to rise again. In the case of the poly(tBuMA) blend, 20 wt% MeCD

raised the Tg approximately 5 °C when compared to the pure bulk polymer film. This

data suggests that with incorporation of up to 20 wt% MeCD into a polymer film of

poly(tBuMA) and poly(CMA) can produce optically clear films to the eye while at the

same time controlling the Tg within a range of approximately 20 °C for poly(tBuMA) and

approximately 10 °C for poly(CMA).

22 Samus, M.A.; Rossi, G. Macromolecules 1996, 29(6), 2275.23 Rossi, G. Trends Polym. Sci. 1996, 4(10), 337.24 Sears, J.K.; Touchette, N. W. Enc. Polym. Sci. Eng. 1989, S, 568.25 Salamone, J. C. (ed) Polym. Mater. Enc. 1996, 7, 5301.


96

5.4 Conclusions

High molecular weight polymers of tBuMA, CMA, and 2EHMA were

synthesized from bulk at 70 °C with BPO as initiator. These polymers were utilized as

references for the physical properties of the polymers produced by cyclodextrin

mediation and were also used in the production of 1 mm thick, optically clear films as

cast from chloroform with up to 20 wt% MeCD incorporated. These blends were

analyzed by DSC, and it was found that Tg’s could be controlled within up to a 20 °C

range due to the apparent plasticizing effects of low concentrations of MeCD (<10 wt%)

and stiffening effects at higher concentrations.

Phillip H. Madison, IV Chapter VI: Cyclodextrin Mediated Polymerizations in Ethylene Glycol

97

CHAPTER VI: Cyclodextrin MediatedPolymerizations in Ethylene Glycol

Abstract

Hydrophobic methacrylic monomers were polymerized in ethylene glycol using

methylated (1.8)-β-cyclodextrin (MeCD) additives. Hydrophobic monomers t-butyl

methacrylate (tBuMA), cyclohexyl methacrylate (CMA), and 2-ethylhexyl methacrylate

(2EHMA) were each dissolved in chloroform with MeCD. Chloroform was then

evaporated to yield solid monomer/cyclodextrin complexes. Complexes were shown by1H NMR and thermogravimetric analysis (TGA) to have molar ratios of monomer to

MeCD as high as 0.72/1.00. The soluble complexes were readily polymerized in ethylene

glycol using free radical initiation. During polymerization, hydrophobic methacrylic

polymers precipitated and the MeCD remained in solution. Poly(alkyl methacrylates)

synthesized via this method exhibited number average molecular weights ranging from

40,000 to 100,000 g/mole with polydispersities from 2.0-4.2 depending on monomer

structure. The molecular weights achieved in ethylene glycol were shown to be

systematically lower than those preformed in aqueous media. The number average

molecular weights for the polymerizations in ethylene glycol were shown to be as much

as 60,000 lower than those performed in aqueous media. This is proposed to be the result

of substantial chain transfer from the methacrylates to ethylene glycol.


98

6.1 Introduction

In this project the success found in the aqueous polymerizations of the

methacrylic/carbohydrate complexes is carried over to an alternative solvent. Ethylene

glycol was chosen as the solvent for these polymerizations for several reasons. For

example, it has been used extensively in step growth polymerizations and is one of the

monomers used in the synthesis of poly(ethylene terephthalate) (PET). PET is widely

utilized in many applications from textiles to soda bottles.1,2,3,4,5,6,7,8 Due to the

widespread use, PET has also become a relatively cheap synthetic polymer, and is

therefore desired for many applications. However, in many cases its properties do not

meet the standards required for the specific application. One area that has been

researched involves the blending of PET with small amounts of a copolymer in order to

improve a desired attribute.9,10,11,12,13,14,15

In many cases PET is blended with acrylic polymers to improve or alter its

properties in order to make the inexpensive commodity useful for specific applications.

For example, blends incorporating nitrile rubber and methacrylic compatibilizers were

prepared for the purpose of producing thermoplastic elastomers with up to 50 wt%

PET.16,17 These blends were heated to allow for light transesterification of the films,

1 Hoerold, S.; Wanzke, W.; Scharf, D. Recent Adv. Flame Retard. Polym. Mater. 1999, 10, 278.2 Reese, G. Fibres Finished Fabr., Pap. Fibre Sci./Dyeing Finish. Groups Jt. Conf. Paper No 2/1-2/11,Textile Institute; UK 1999 .3 De Gryse, R.; Lievens, H. Proc. Int. Conf. Vac. Web. Coat. 11th 1997 16.4 Kublar, V.; Winckler, L. U. S. Patent 6143387 A 20001107 2000.5 Sirdharan, K. Pop. Plast. 1973, 18(4), 17.6 Belvroy, R.; VanVeenen, W. PCT Int. Appl. 1999.7 Cornell, S. PCT Int. Appl. 1998.8 Gabriele, M. Mod. Plast. 1997, 74(4), 60.9 Kim, D.; Park, K.; Kim, J.; Suh, K. J. Appl. Polym. Sci. 2000, 78(5), 1017.10 Chiriac, M.; Chiriac, V.; Vasile, C.; Burlacel, M. Int. J. Polym. Mater. 1999, 44(1-2), 73.11 Lepers, J.; Favis, B.; Kent, S. Polymer 2000, 41(5), 1937.12 Ma, D.; Zhang, G.; He, Y.; Ma, J.; Luo, X. J. Polym. Sci., Part B: Polym. Phys. 1999, 37(21), 2960.13 Kim, W.; Kang, H. Annu. Tech. Conf. – Soc. Plast. Eng. 1998, 56(2), 1561.14 Tanrattanakul, V.; Hiltner, A.; Baer, E.; Perkins, W.; Massey, F.; Moet, A. Polymer 1997, 38(9), 2191.15 Cook, W.; Moad, G.; Fox, B.; Van Deipen, G.; Zhang, T.; Cser, F.; McCarthy, L. J. Appl. Polym. Sci.1996, 62(10), 1709.16 Papke, N.; Karger-Kocsis, J. Polymer 2000, 42(3), 1109.17 Papke, N.; Karger-Kocsis, J. Annu. Tech. Conf. – Soc. Plast. Eng. 2000, 58(3), 3271.


99

which gave the films their thermoplastic elastic behavior.18,19 Blends of PET with

various methacrylic homopolymers and copolymers and have shown to exhibit

substantial increases in impact strength as opposed to pure PET.20,21,22

This chapter deals with the cyclodextrin mediated polymerizations of

methacrylates in ethylene glycol. Methacrylic/carbohydrate complexes were dissolved in

ethylene glycol and initiated with potassium persulfate. These reactions behaved similar

to the polymerizations carried out in aqueous solution. The resulting polymer

precipitated out during the reaction and the majority of the cyclodextrin remained

dissolved in the ethylene glycol. This is potentially the first step in a novel approach to

blending methacrylic polymers and polyesters in which the next step would involve the

addition of a suitable comonomer for ethylene glycol and the subsequent step-growth

polymerization of the direct reaction mixture.

6.2 Experimental

Purification: All monomers and initiators were purchased from Aldrich and used as

received unless otherwise stated. MeCD was generously donated by Wacker-Chemie and

was used as received. Monomers were vacuum distilled (0.5 mm Hg) from CaH2 using

the freeze-thaw method to degas the monomer and stored at –25 °C under nitrogen.

Complexation: Complexations of tBuMA, 2-EHMA, nBuMA, and CMA were

preformed in 200 mL of chloroform with concentrations of approximately 0.04 M of both

MeCD and monomer. Approximately 10.0 g (7.6 mmol) of MeCD and a molar

equivalent of monomer were added to 200 mL of chloroform in a 500 mL erlenmeyer

flask. The solution was stirred for 24 h at room temperature. Chloroform was then

removed using a rotoevaporator and the complex was dried in vacuo at 70 °C for 24

18 Jha, A.; Bhowmick, A. Polymer 1997, 38(17), 4337.19 Granalos, K.; Kallitsis, J.; Kalfoglou, N. Polymer 1995, 36(7), 1393.20 Wu, J.; Xue, P.; Mai, Y. Polym. Eng. Sci. 2000, 40(3), 786.21 Abu-Isa, I.; Jaynes, C.; O’Gara, J. J. Appl. Polym. Sci. 1996, 59(13), 1957.22 Penco, M.; Pastorino, M.; Occhiello, E.; Garbassi, F.; Braglia, R.; Giannotta, G. J. Appl. Polym. Sci.1995, 57(3), 329.


100

hours. Isolated yields ranged from 90-96 % and ratios of monomer to MeCD ranged

from 0.50/1.00 to 0.75/1.00.

Aqueous Homopolymerizations: Homopolymerizations of the complexes were

conducted in a 50 mL 1-necked, round-bottomed, flask with 20.0 mL de-ionized water,

1.00-9.00 weight % (1.36-17.10 mol %) K2S2O8 compared to monomer, and 2.00 g of

complex. The polymerization reactor was then septum capped and sparged with ultra-

pure nitrogen for 5-10 min prior to initiator addition. Polymerization was conducted



MeCD was recovered by removing the water with a rotoevaporator and drying in vacuo

for 18 hrs at 80 °C.

Homopolymerizations in Ethylene Glycol: Homopolymerizations of the complexes

were conducted in a 50 mL 1-necked, round-bottomed, flask with 20.0 mL ethylene

glycol, 1.00-9.00 weight % (1.36-17.10 mol %) K2S2O8 compared to monomer, and 2.00

g of complex. The polymerization reactor was then septum capped and sparged with

ultra-pure nitrogen for 5-10 min prior to initiator addition. Polymerization was conducted



MeCD was recovered by removing washing ethylene glycol with 2, 20mL aliquots of

chloroform, subsequent removal of chloroform with a rotoevaporator, and drying in

vacuo for 24 hrs at 100 °C.





Elmer Pyris 1 under N2 atmosphere, from 25 °C to 200 °C at a heating rate of 10 °C/min.




101

Thermogravimetric analysis (TGA) was utilized under N2 atmosphere using a Perkin-

Elmer TGA7 and heating cycles varied.


Methacrylic/MeCD complexes were prepared in chloroform solvent (Scheme

6.1). The cyclodextrin utilized in this study was a methylated derivative of beta-

cyclodextrin (1.8 out of 3.0 hydroxyl groups present on each glucose ring were converted

to methoxy groups). As reported previously, complexation times of 24 h appeared to be

sufficient to achieve ratios of methacrylate to cyclodextrin in complex as high as 0.72 to

1.00. These complexes were then dried and used in polymerizations in ethylene glycol as

solvent(Scheme 6.1).

Polymerization in ethylene glycol gave similar results when compared to the

aqueous polymerizations of the complexes. None of the polymers or uncomplexed

monomers were shown to have appreciable solubility in ethylene glycol. However, the

reaction started out homogeneous with the complexes dissolved in solution. After some

time, the polymer precipitated out of solution gradually. The time it took for the

polymers to begin to precipitate from solution was investigated, however, the results were

inconclusive. The precipitation onset times for any given system were observed to be

erratic and statistically insignificant.


102

R' = H or Me

7

CHCl324 hrs

25 oC O

O

RO

O

R

+O

O

OR'R'O

OR'

R = or or

OO

R

OO

O O

R R

K2S2O8

EthyleneGlycol

50-70 oC,24 hrs

+

Step #1

Step #2

or

O

O

OR'R'O

OR'

7

R' = H or Me

Scheme 6.1 Preparation of the monomer/MeCD complex (Step 1), and subsequentpolymerization in ethylene glycol (Step 2).

After 24 hours the precipitated product was then easily filtered to give polymer

with trace amounts of MeCD. This data is consistent with data obtained from the MeCD

mediated polymerizations of methacrylates in aqueous media which were also shown to

have similar amounts of MeCD in the polymer. These polymers were dried, molecular

weights were obtained by GPC, and the results are listed in Tables 6.1-4. 1H NMR was

also used to determine percent yields and residual cyclodextrin content in the product.

This, however, proved inaccurate as yields above 100% were observed. From previous

CPK studies and knowledge of ethylene glycol structure through CPK studies it is

proposed that ethylene glycol can be readily accommodated within the cyclodextrin

cavity. It was concluded that some of the residual cyclodextrin in the polymer was

complexed with ethylene glycol.


103

Drying time and temperature were subsequently increased in order to evolve the

residual ethylene glycol from the polymer. However even with drying temperatures as

high as 120 °C and times as long as 3 days it was observed that residual ethylene glycol

still remained. From previous TGA analysis (Chapter 2.3) it was observed that rate of

evaporation of a compound is substantially reduced upon complexation with

cyclodextrin. From this observation and the data indicating the presence of ethylene

glycol even after increased drying times and temperatures it was concluded that the

ethylene glycol/cyclodextrin complex was present in the precipitated polymer.

In order to remove the residual cyclodextrin and ethylene glycol the polymer

products were reprecipitated from tetrahydrofuran into a ten times volume excess of

water. Figure 6.1 shows the GPC of a resulting poly(CMA) polymer before and after

reprecipitation and subsequent drying. The crude polymer shows a peak around 25.5 min

which is characteristic of cyclodextrin. A GPC of pure cyclodextrin was run to confirm

its elution time. 1H NMR of the polymers was also performed before and after

reprecipitation. Figure 6.2 shows a 1H NMR of a poly(CMA) sample before and after

reprecipitation and there was found to be no signals characteristic of cyclodextrin present

in spectrum of the reprecipitated product.


104

Table 6.1 Polymerizations of t-butyl methacrylate under specified conditions.


(°°C)Mn

a

(g/mol)Mw

Mn

poly(tBuMA)1

poly(tBuMA)2

poly(tBuMA)3

A

B

A

50

50

60

56,300

47,400

41,300

2.59

2.84

2.69

Table 6.2 Polymerizations of n-butyl methacrylate under specified conditions.


(°°C)Mn

a

(g/mol)Mw

Mn

poly(nBuMA)1

poly(nBuMA)2

poly(nBuMA)3

A

B

A

50

50

60

50,100

59,400

49,600

3.29

2.65

2.00

Table 6.3 Polymerizations of cyclohexyl methacrylate under specified conditions.


(°°C)Mn

a

(g/mol)Mw

Mn

poly(CMA)1

poly(CMA)2

poly(CMA)3

poly(CMA)4

A

B

A

A

50

50

60

70

100,000

72,300

75,700

36,100

2.97

4.05

2.48

4.19

Table 6.4 Polymerizations of 2-ethylhexyl methacrylate under specified conditions.


(°°C)Mn

a

(g/mol)Mw

Mn

poly(2EHMA)1

poly(2EHMA)2

poly(2EHMA)3

poly(2EHMA)4

A

B

A

A

50

50

60

70

281,000

194,000

136,000

59,000

2.29

2.26

2.60

2.33a- Waters GPC with external 410 RI detector and Viscotek 150R viscometer, NMP/P2O5 (0.02 M)


Conditions:A-Polymerization from the complex in water initiated with 1.0 weight% K2S2O8

B-Polymerization from the complex in water initiated with 9.0 weight% K2S2O8


105

Figure 6.1 GPC chromatographs of poly(CMA) that was prepared using the complexbefore (green) and after (red) repricipitaion from THF into 10x vol of water.

This reprecipitation data also confirms that chain transfer to cyclodextrin is

negligible. GPC indicates free cyclodextrin in the polymer product and 1H NMR shows

the complete absence of cyclodextrin resonances after reprecipitation. This is consistent

with early studies where the chain transfer to cyclodextrin was found to be negligible.23,24

Typical reprecipitated yields ranged from 70-85% and the Tgs were consistent with those

measured from bulk polymerizations (Chapter 5).

23 Maciejewski, M. J. Macromol. Sci. – Chem. A13(1) 1979 77.24 Maciejewski, M.; Gwizdowski, A.; Peczak, P.; Pietrzak, A. J. Macromol. Sci. – Chem. A13(1) 1979 87.


106

Figure 6.2 1H NMR spectrum of poly(CMA) that was prepared using the complex before(top) and after (bottom) reprecipitation from THF into 10x vol of water.

In order to assess the effect of complexation with MeCD on these polymerizations

controls were run in which reactions were run in the absence of MeCD. The product

obtained from these reactions were low molecular weight oils with yields much less than

1.0 %. However, polymerization of the complexes in ethylene glycol resulted in high

molecular weight polymers with reprecipitated yields as high as 85 %. It should be noted

that the molecular weight data for the polymerizations in ethylene glycol were obtained

from the crude product before reprecipitation, so direct comparison can be made to those

polymers synthesized in water. Tables 6.5-6 offer a comparison of the products obtained

from the polymerizations of tBuMA and CMA complexes in both water and ethylene

glycol.


107

Table 6.5 Comparison of the results from the polymerizations of the CMA/MeCDcomplex in water and ethylene glycol.

SolventTemperature

(°°C)wt% Initiator to

MonomerMn

a Mw

Mn

Water 50 1.0 142,000 5.91

Water 50 9.0 93,200 4.39

Water 60 1.0 69,100 6.24

EthyleneGlycol

50 1.0 100,000 2.97

EthyleneGlycol

50 9.0 72,000 4.05

EthyleneGlycol

60 1.0 75,300 2.48



Table 6.6 Comparison of the results from the polymerizations of the tBuMA/MeCDcomplex in water and ethylene glycol.



SolventTemperature

(°°C)wt% Initiator to

MonomerMn

a Mw

Mn

Water 50 1.0 137,000 3.45

Water 50 9.0 90,000 3.69

Water 60 1.0 48,700 3.62

EthyleneGlycol

50 1.0 56,100 2.59

EthyleneGlycol

50 9.0 47,900 2.84

EthyleneGlycol

60 1.0 41,200 2.69


108

The first notable difference between the data from those polymers s ynthesized in

water and those synthesized in ethylene glycol is that for under a given set of conditions

the polymers obtained from ethylene glycol systematically exhibit lower number average

molecular weights than those obtained from water. However, it has been shown that

ethylene glycol has a significant chain transfer constant. Chain transfer constants for

methyl methacrylate to ethylene glycol at 60 and 80 °C are 0.28 x 10-4 and 0.60 x 10-4

respectively.25 Therefore it was concluded that the systematic decrease in molecular

weight from those polymers obtained from ethylene glycol could be attributed to chain

transfer to solvent during polymerization.

Table 6.7 Chain transfer constants for methyl methacrylate to various organic solvents.25

Solvent Temperature (°°C) Transfer Constant (x104)

60 0.394Butyl Alcohol

80 0.25

60 0.28Ethylene Glycol

80 0.60

60 0.25Toluene

80 0.52

60 0.20Methanol

80 0.33

25 Brandrup, J.; Immergut, E.; Grulke, E. (eds) Polymer Handbook, 4th ed. John Wiley & Sons, Inc.; NY,1999.


109

The second notable difference between the two types of polymerizations is that

the ethylene glycol reactions appear to also result in a narrower molecular weight

distribution. The molecular weight distributions differ by as much as a factor of two.

This decrease in polydispersity is not well understood. The lowering of molecular weight

distribution could be due to a number of factors. A more detailed understanding of the

mechanism involved in these reactions is needed in order to predict the effect changing

different reaction parameters. One theory is that the difference in molecular weight

distributions is a result of a more controlled reaction in the case of ethylene glycol. This

increase in control could presumably be caused by differences in the relative solubility of

the reaction components in water versus ethylene glycol. Further work is needed in order

to fully understand these types of polymerizations.

However, regardless of the specific mechanism involved the data indicates that

the MeCD mediated reactions in ethylene glycol were successful and that they followed

the same trend as far as molecular weights achieved, yields, and precipitated state of the

final product. High molecular weight polymer was obtained in ethylene glycol with a

notable reduction in molecular weight distribution when compared to the reactions done

in water, and control of molecular weights was achieved by varying either temperature or

initiator concentration. Isolation of product was easily achieved through simple vacuum

filtration of the precipitated polymer and the MeCD could be recovered by washing the

post-reaction ethylene glycol solution with chloroform, and subsequent evaporation of

the chloroform.

6.4 Conclusions

Polymerizations of MeCD/methacrylate complexes in ethylene glycol were

successful. Chain transfer to ethylene glycol was found to be significant for these

polymerizations and reduced molecular weights compared to these reactions done in

water by as much as 60,000. Chain transfer to MeCD, however, was found to be

negligible through both the GPC analysis of the product and also 1H NMR analysis

before and after reprecipitation from THF into 10x volume of methanol. Molecular

weights ranging from 40,000-100,000 were obtained with acceptable molecular weight


110

distributions and isolated, reprecipitated yields as high as 85%. Molecular weights were

controlled as in the aqueous polymerizations through manipulation of either temperature

or initiator concentration.

Phillip H. Madison, IV Chapter VII: Synthesis of a Side Chain Liquid Crystalline Monomer for Subsequent MeCD Mediated Aqueous Polymerizations

111

Chapter VII: Synthesis of a Novel, Side Chain LiquidCrystalline Monomer and Subsequent Cyclodextrin

Mediated Aqueous Polymerization

Abstract

The side chain liquid crystalline monomer, 6-(4’-hexyloxy-biphenyl-4-yloxy)-

hexyl methacrylate was synthesized in high purity via a three-step procedure. The

monomer was purified through column chromatography. Product purity was confirmed

by a combination of mass spectrometry, thin layer chromatography, and 1H and 13C

NMR. This hydrophobic monomer was subsequently complexed with 1-3 equvalents of

methylated(1.8)-β -cyclodextrin in an attempt to alter the water solubility of the

monomer. It was found that with ratios of 1-3:1 of cyclodextrin to 6-(4’-hexyloxy-

biphenyl-4-yloxy)-hexyl methacrylate the water solubility of the monomer was not

changed enough to allow for preparation of a solution acceptable for polymerization.


112

7.1 Introduction

Cyclodextrin (CD) has been used to complex a variety of compounds for a

number of different applications. Their ability to form host guest complexes has been

utilized in consumer products ranging form chewing gum1 to detergent2 and has been

incorporated into chemical processes3,4 and drug delivery systems.5,6,7,8,9,10,11,12 Figure

6.113,14,15,16,17,18,19,20 gives a few examples of some to the compounds that have been used

in the formation of inclusion complexes with β-CD in the past few years. Acridine Red,

Rhodamine B, 8-anilino-1-naphthalenesulfonic acid, and 2-(p-toluidino)naphthalene-6-

sulfonic acid are examples of flouressent dyes, homocysteine is a compound that plays a

role in the methyl-folate trap; a biological reaction involved in cell production,21

ciprofloxacin is an antibiotic, and 2,6-naphthalenedicarboxylic acid is an important

monomer for the synthesis of main chain liquid crystalline polymer systems.

1 Sato, Y.; Suzuki, Y.; Ito, K.; Shingawa, T. US Patent 5156866 1992.2 Szejtli, J.; Osu, T. ed. Comprehensive Supramolecular Chemistry Elsevier Science Ltd; Tarrytown, NY;1996.3 Shieh, W.; Hedges, A. US Patent 5371209 1994.4 Lau, W.; Shah, B. US Patent 5376709 1994.5 Uekama, K.; Hirayama, F.; Irie, T. Chem. Rev. 1998, 98(5), 2045.6 Gonzalez, H.; Hwang, S.; Davis, M. Bioconjugate Chem. 1999, 10(6), 1068.7 Bibby, D.; Davies, N.; Tucker, I. J. Microencapsulation 1998, 15(5), 629.8 Duchene, D.; Wouessidjewe, D.; Ponchel, G. Journal of Controlled Release 1999, 62, 263.9 Wulff, M.; Alden, M. European Journal of Pharmaceutical Sciences 1999, 8, 269.10 Bibby, D.; Davies, N.; Tucker, I. International Journal of Pharmceutics 1999, 187, 243.11 Miro, A.; Quaglia, F.; Calignano, A.; Barbato, F.; Capello, B.; Rotonda, M. S. T. P. Pharma Sciences2000, 10(2), 157.12 Ooya, T.; Yui, N. Critical Reviews in Therapeutic Drug Carrier Systems 1999, 16(3), 289.13 Yu, L.; You, C. J. Phys. Org. Chem. 2001, 14(1), 11.14 Kim, I.; Park, S.; Kim, H. J. Chromatogr., 2000, A 877(1&2), 217.15 Bergamini, J. Belabbas, M.; Jouini, M.; Aeiyach, S.; Lacroix, J.; Chane-Ching, K.; Lacaze, P. J.Electroanal. Chem. 2000, 482(2), 156.16 Shiraishi, Y.; Toshima, N.; Kawamura, T.; Mihori, H.; Shirai, H.; Hirai, H. J. Mol. Catal. A: Chem.1999, 139(2-3), 149.17 Maafi, M.; Aaron, J.; Lion, C. Proc.-Indian Acad. Sci., Chem. Sci. 1998, 110(3), 319.18 Herrmann, W.; Wehrle, S.; Wenz, G. Chem. Commun. 1997, 18, 1709.19 Aithal, K.; Udupa, N. Pharm. Sci. 1996, 2(10), 451.20 Mielcarek, J. Acta Pol. Pharm. 1996, 53(6), 411.21 Combs,G. The Vitamins-Fundmental Aspects in Nutrition and Health Academic Press, Inc; NY 1992.


113

Figure 7.1 Names and structures of typical compounds utilized recently in the formationof host-guest complexes with β-CD derivatives.13,14,15,16,17,18,19,20

ONH NH

O

CO2H

(Et)2N N(Et)2

SO3H HN HO3S

NH

N

O

N

F

SH2N

O

O

HS

NH2

O

OH

NO2

OH

OH

HO

O

O

(Me)2N N(Me)2

HN N

N

CO2H

OF

N

O

O

N

O

O

NO2NicardipineCiprofloxacin

(Z)-4,4'-bis(dimethylammoniummethyl)stilbene

2,5 norbornadiene

2,6 naphthalenedicarboxylic ac

4-nitrophenol

homocysteine

4-aminosulfonyl-7-flouro-2,1,3-benzoxadiazole

2-(p-toluidino)naphthalene-6-sulfonic acid

8-anilino-1-naphthalenesulfonic acid

Acridine Red

Rhodamine B


114

There has been substantial research devoted recently to the development of novel

side-chain liquid crystalline acrylic systems. Recent research efforts include the study of

fluorescent chromophores as side chain mesogenic units where the fluorescent

characteristics are examined in the various liquid crystalline phases observed,22 and

examinations of liquid crystalline systems with photo-crosslinking potential.23,24

Examinations of side chain mesogens with the capability to hydrogen bond have also

been studied,25,26,27 and there have also been cases where chemical crosslinks were

introduced to produce elastomeric liquid crystalline materials.28,29 More fundamental

studies also have been conducted on the length and structure of the spacer required to

achieve specific liquid crystalline mesophases,30,31 and it has been found that the spacer

required to achieve liquid crystallinity can vary from system to system.32

There have been a several of publications dealing with the inclusion complexation

of liquid crystalline moieties with cyclodextrins.33,34 In most cases the guest compounds

were small molecule liquid crystalline materials. In this chapter, the synthesis procedure

of a monomer used in the synthesis of side chain liquid crystalline polymers is described.

Characterization of the compounds formed from each of the three steps in the procedure

are also described and include mass spectrometry, 1H and 13C NMR spectroscopy, and

thin layer chromatography. Recrystallization and column chromatography were also

used for the purpose of purification. Lastly discussed, will be the complexation of the

22 Chiellini, E.; Houben, J. L.; Wolff, D.; Galli, G. Mol. Cryst. Liq. Cryst. Sci. Technol., Sect A 2000, 352,439.23 Kawatsuki, N. Recent Tes. Dev. Polym. Sci. 1998, 2(pt. 2), 277.24 Talroze, R. V.; Aubarev, E. R.; Merekalov, A. S.; Vasilets, V. N.; Yuranova, T.I.; Kovalchuk, A. Polym.Prepr. 1996, 37(1), 54.25 Mihara, T.; Kokubun, T.; Koide, N. Mol. Cryst. Liq. Cryst. Sci. Technol., Sect. A 1999, 330, 1479.26 Wu. X. D.; Zhang, G. L.; Zhang, H. Z. Macromol. Chem. Phys. 1998, 199(10), 2101.27 Kawakami, T.; Kato, T. Macromolecules 1998, 31(14), 4475.28 Symons, A.J.; Davis, F. J.; Mitchell, G. R. Polymer 1999, 40(19), 5365.29 Raja, V. N.; Kang, S. W.; Lee, J. S.; Lee, J. S.; Lee, J. C. Mol. Cryst. Liq. Cryst. Sci. Technol., Sect. A1997, 301, 157.30 Kawatsuki, N.; Sakashita, S.; Taktani, K.; Yamamoto, T.; Sangen, O. Macromol. Chem. Phys. 1996,197(6), 1919.31 Scherowsky, G.; Mueller, U.; Springer, J.; Trapp, W.; Levelut, A. M.; Davidson, P. Liq. Cryst. 1989,5(4), 1297.32 Kim, K.; Hatanaka, K.; Uryu, T. J. Polym. Sci., Part A: Polym. Chem. 2000, 38(8), 1214.33 Nishijo, J.; Mizuno, H. Chem. Pharm. Bull. 1998, 46(1), 120.34 Green, M.; Jha, S.; Muellers, B.; Park, J.; Shultz, G.; Kremers, J. Polym. Mater. Sci. Eng. 1996, 75, 450.


115

liquid crystalline monomer synthesized with methylated (1.8)-β-cyclodextrin for the

purpose of subsequent polymerization of the complex in a non-solvent to the monomer.

7.2 Experimental

Purification: Triethyl amine, methacroyl chloride, biphenol, potassium carbonate,

bromohexane, bromohexanol, and potassium persulfate were bought from Aldrich and

used as received. MeCD was generously donated by Wacker-Chemie and was used as

received.

Synthesis of liquid crystalline monomer: 5.0 g of biphenol and 2.23 g (0.5 eq) of

potassium carbonate were added to 100 mL of ethanol in a 2 necked, 250 mL, round-

bottomed flask. The flask was purged with nitrogen and heated to 78 °C under a nitrogen

atmosphere. The solution was refluxed by water cooled condenser for 1h. 4.44 g (1.0 eq)

of bromohexane was then mixed with 40 mL of ethanol and added to the reactor

dropwise over a 2 h period by introduction with an addition flask. The addition flask was

then removed and the solution allowed to reflux for an additional 24 h.

TLC was used to moniter extent of reaction and upon completion 1H NMR

indicated a product that was 85 % monosubstituted and 15 % disubstituted. The mono-

substituted product was purified via flash chromatography in an 80/20 hexane/ethyl

acetate mixture. Solvent was removed by rotoevaporator and the product was dried in

vacuo at room temperature for 24 h. 1H NMR was used to confirm product purity.

Isolated yield was found to be 36 %.

The monosubstituted hexane biphenol was redissolved in 100 mL of ethanol in a

2-necked, 250 mL, round-bottomed flask. The reactor was then charged with 2 eq of

potassium carbonate and sparged with nitrogen. The reactor was then heated to 78 °C

and refluxed for 1h. 1.08 eq of 6-bromohexanol was dissolved in 40 mL of ethanol and

added to an addition funnel. The 6-bromohexanol solution was then added dropwise over

a 2 h period and then the reactor was left to reflux for an additional 48 h. Extent of


116

reaction was monitered by TLC. Upon completion the ethanol content was reduced by

removal through a rotoevaporator. The solution was then precipitated into water and the

product was filtered, dried and recrystallized from dichloromethane. Product was

collected by filtration and dreid invacuo at room temperature for 24 h. 1H NMR was

used to confirm product purity. Isolated yield was found to be 82 %.

The product was then dissolved in 100 mL of THF with 1.6 eq of triethyl amine in

a 2-necked, 250 mL, round-bottomed flask. The reactor was sparged with nitrogen and

cooled in an icebath. 1.3 eq of methacroyl chloride was then added dropwise via syringe.

After 2 h the ice bath was removed and the reactor was allowed to warm to room

temperature. The solution was left to react for an additional 24h. Extent of reaction was

monitered by TLC. Product was purified by flash chromatography through a silica

column with a 70/30 hexane/dichloromethane mixture. The product was then collected

by removal of solvent by rotoevaporator and drying invacuo at room temperature for 24

h. Product was confirmed by mass spectrometry and 1H and 13C NMR. Isolated yield

was found to be 16 %.

Complexation: Complexation was preformed in 20 mL of chloroform with

concentrations of approximately 0.04-0.12 M of MeCD and 0.04 M of monomer.

Approximately 2.00 g of monomer and 1.0-3.0 molar equivalents of MeCD were added

to 20 mL of chloroform in a 50 mL erlenmeyer flask. The solution was stirred for 24 h at

room temperature. Chloroform was then removed using a rotoevaporator and the

complex was dried in vacuo at 70 °C for 24 h. Isolated yields ranged from 90-96 %. All

complexes with up to 3.0 eq of MeCD were insoluble in aqueous solution.

Characterization: DSC analysis was preformed using a Perkin Elmer Pyris 1 under N2

atmosphere, from 25 °C to 200 °C at a heating rate of 10 °C/min. All NMR spectra were

obtained in CDCl3 using a Varian 400 MHz NMR. Mass spectrometry (MS) was done

through electron ionization (EI-) technique under high vacuum and temperature.


117


These research efforts have established well the cyclodextrin mediated

polymerizations of the methacrylic monomers chosen in both aqueous solution and in

ethylene glycol. It was decided that it would be interesting to examine the novel

cyclodextrin mediation of a monomer from which a liquid crystalline polymer (LCP)

could be synthesized. The monomer represented in Figure 7.1 was chosen because it

was expected to be suitable for complexation with cyclodextrin. Also, the cyclodextrin

mediated aqueous polymerization of such a monomer complex would be novel and may

offer interesting insight into the mechanism involved.

Figure 7.1 Chemical structure of methacrylic acid 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl ester.

The first step in the synthesis of the liquid crystalline monomer involved the

selective synthesis of the mono-n-hexoxy substituted product of biphenol.(Scheme 7.1)

O OO

O


118

Scheme 7.1 Three step synthesis procedure for the liquid crystalline monomer, 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate

O OH

Reflux for 24 h

Added bromohexane (1eq) in ethanol over 2 h period

K O OH

Reflux in ethanol78 oC

K2CO3(0.5eq)OHHO

78 oC78 oC

O

O

HO

Reflux for 2 days

Add bromohexanol (1.08eq) in ethanol over 2h

O

O-K+

Reflux in ethanol

K2CO3 (2.0eq)

O

OH

O

O

O

OTHF

N(Et)3, 0 oC

Add methacryloyl chloride in THF dropwise

O

O

OHStep 3

Step 2

Step 1


119

In this first step biphenol was refluxed in ethanol (78 °C) in the presence of 0.50

equivalents of K2CO3 for 2 h in order to deprotonate an average of only one of the phenol

groups. 1.00 equivalent of bromohexane was then added drop wise over a period of 2h.

The reaction was then allowed to reflux for an additional 24 h. The reaction was

monitored by thin layer chromatography (TLC) to determine extent of reaction. The

major products formed in this step were the desired monosubstituted biphenol and the

disubstituted byproduct. This was confirmed by a combination of TLC and 1H NMR.

The two compounds were separated using column chromatography with an

elutent composed of an 80/20 mixture of hexane and ethyl acetate. Both the byproduct

and desired product were collected and isolated by removal of solvent with a

rotoevaporator. Figures 7.2-3 show the 1H NMR spectrums of the disubstituted

byproduct and desired monosubstituted product respectively. This reaction gave an

isolated yield of monosubstituted product of 36 %. The 1H NMR spectrum and TLC

indicated that the desired product, 4-hexoxy-4’-biphenol was pure after column

chromatography was used so the product was then directly utilized in the next step.

The second step involved refluxing the 4-hexoxy-4’-biphenol produced in the first

reaction in the presence of 2.00 equivalents of K2CO3 in ethanol for two hours in order to

deprotonate the remaining phenol. 1.08 equivalents of bromohexanol was then added

drop wise to the reactor over a 2 h period. The reaction was then left to continue at

ethanol reflux for 48 h and the extent of reaction was monitored by TLC. Upon

completion the ethanol volume was reduced by rotoevaporator and the solution was then

precipitated into water and the product was filtered off. 1H NMR of this product

indicated impurities; therefore the crude product was recrystallized from

dichloromethane. The purified product was then filtered off and dried invacuo for 24 h.1H NMR was used to confirm product purity (Figure 7.4) and isolated yield of pure

product was 82 %.


120

Figure 7.2 1H NMR spectrum of the 4’-hexoxy-biphenyl-4-yloxy hexane byproduct from the first step in the liquid crystallinemonomer synthesis scheme.


121

Figure 7.3 1H NMR spectrum of the desired product, 4-hexoxy-4’-biphenol from the first step in the liquid crystalline monomersynthesis scheme.


122

Figure 7.4 1H NMR spectrum of the desired product, 6-(4’-hexoxy-biphenyl-4-yloxy)-hexanol from the second step in the liquidcrystalline monomer synthesis scheme.

Phillip H. Madison Chapter VII: Synthesis of a Side Chain Liquid Crystalline Monomer for Subsequent MeCD Mediated Aqueous Polymerizations

123

The final step in the synthesis of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl

methacrylate involved the reaction of the 6-(4’-hexoxy-biphenyl-4-yloxy)-hexanol with

methacroyl chloride. This reaction was performed in THF distilled from CaH2. The 6-

(4’-hexoxy-biphenyl-4-yloxy)-hexanol was dissolved in THF with 1.6 equivalents of

triethyl amine and the reactor temperature was lowered to 0 °C by surrounding with an

ice water bath. 1.3 equivalents of methacroyl chloride was then added drop wise via

syringe. After 2 h the ice bath was removed and the reaction left to proceed for an

additional 24 h. After 24 h TLC and 1H NMR analysis of products indicated low yield so

the reaction was left to react for an additional 24 h. TLC and 1H NMR analysis at this

point showed no further reaction during the second 24 h of reaction so the experiment

was concluded. Column chromatography with an elutent mixture composed of 70/30

hexane/dichloromethane was used to purify the product. The purified isolated yield,

however, was found to be a low 16 %. It is proposed that this low yield is due to

impurities in the methacroyl chloride, which was neither distilled prior to reaction, nor

stored properly at low temperature under nitrogen. 1H NMR of the purified 6-(4’-

hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate is shown, in Figure 7.5 to be fairly pure.

Also the 13C NMR of both the presursor, 6-(4’-hexoxy-biphenyl-4-yloxy)-hexanol

and the final product are presented (Figure 7.6). These 13C NMR also indicate a pure

product, and peak assignments are made based on previous liturature35,36 and model

compounds.37 The most notable difference in the two spectrum are the peaks in the

spectrum of the final liquid crystalline monomer that are not present in the precursor.

The four new peaks at 161, 137, 125, and 18 ppm correspond to the carbonyl carbon, two

sp2 carbons of the unsaturation, and the methyl on the methacroyl group respectively.

There are also several significant shifts that occur in the carbons closest to the site of

35 Finkelmann et al. Makromol. Chem. 1978, 179, 2541.36 Ullrich, K.; Wendorff, J. Mol. Cryst. Liq. Cryst. 1985, 131, 361.37 Silverstein. R.; Bassler, G.; Morrill, T. Spectrometric Identification of Organic Compounds, 5th ed. JohnWiley & Sons; NY 1991.

Phillip H. Madison Chapter VII: Synthesis of a Side Chain Liquid Crystalline Monomer for Subsequent MeCD Mediated Aqueous Polymerizations

124

reaction going from precursor to product. The biggest shifts are seen in the

twomethylene groups closest to the site of reaction labeled “k” and “l” in Figure 7.6.


125

Figure 7.5 1H NMR spectrum of the desired product, 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate from the final step in theliquid crystalline monomer synthesis scheme.


126

Figure 7.6 13C NMR spectra of the precursor, 6-(4’-hexoxy-biphenyl-4-yloxy)-hexanol (top) and the desired product, 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate (bottom).


127

In order to further confirm the structure of the final liquid crystalline monomer

mass spectrometry was performed. Figure 7.7 shows the spectrum produced from the

electron ionized mass spectrum collected under high vacuum and temperature. The most

notable feature of the spectrum obtained is the prominent molecular ion peak present at

438, which corresponds to the molecular weight calculated given the composition of the

desired project. The fragmentation peaks found at 398, 354, 270, and 186 are also

consistent with fragmentations expected for the structure of 6-(4’-hexyloxy-biphenyl-4-

yloxy)-hexyl methacrylate. Therefore, in light of the mass spectrometry, 1H NMR, and13C NMR data combined, it was concluded with confidence that the product synthesized

was in fact the desired side-chain liquid crystalline monomer, 6-(4’-hexyloxy-biphenyl-4-

yloxy)-hexyl methacrylate.

Having confidence that the desired product was synthesized steps were then taken

to form the inclusion complex between this monomer and methylated (1.8)-β-

cyclodextrin (MeCD) for the purpose of subsequently dissolving and polymerizing in a

nonsolvent to the monomer such as water (Scheme 7.2). The liquid crystalline monomer

and 1.00 equivalent of MeCD were dissolved in chloroform and stirred for 1 h. This

duration of stirring time was established as being sufficient for the complexation of

methacrylic monomers with smaller ester alkyl groups (Chapter 2). The chloroform was

then removed and the complex was mixed with water at a concentration of 0.1 g/mL.

However, even after stirring for 48 h the complex was not dissolved.


128

Figure 7.7 Electron ionized mass spectrum of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate.


129

Scheme 7.2 Synthesis scheme for the formation of the side-chain liquid crystalline methacrylic monomer/cyclodextrin complex, andsubsequent aqueous polymerization.

O

O

(CH2)6

O

O

(CH2)5

CH3

R' = H or Me

7

O

O

OR'R'O

OR'

+

O

O

(CH2)5

CH3

O

O

(CH2)6

O

O

(CH2)5

CH3

O

O

(CH2)6

n

Complexation H2O

Chloroform K2SO4


130

There have been many instances of host-guest complexations where the ratio of

host to guest have been greater or less than one. 27,28,29,30,31,32,33,34,35,36,37 A main chain

polyrotaxane is a typical example of a case where the ratio of host to guest is

considerabley greater than unity.27,28 Therefore, complexations in which the ratio of

MeCD to monomer was 2:1 or 3:1 were produced in the same fashion as the 1:1

complexes. It was expected that complexation between MeCD and the liquid crystalline

monomer utilized would be favorable given examination of the chemical structure in the

literature that have been utilized,13,14,15,16,17,18,19,20 (Figure 6.1) as well as CPK modeling

studies. CPK modeling indicated that the ester alkyl could be efficiently accommodated

within β-cyclodextrin and that up to three cyclodextrin rings could theoretically be

accommodated by the monomer (Figure 7.7). However, it was found that these 2:1 and

3:1 complexes were also insoluble in water. Therefore, it is proposed that complexation

with cyclodextrin at ratios of 1-3:1 cyclodextrin:monomer does not alter the solubility

properties of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate enough to cause it to

be soluble in aqueous solution.

27 Nepogodiev, S.; Stoddart, J. Chem. Rev. 1998, 98(5), 1959.28 Amabilino, D.; Stoddart, J. Chem. Rev. 1995, 95(8), 2725.29 Shigekawa, H.; Miyake, K.; Sumaoka, J.; Harada, A.; Komiyama, M. J. Am. Chem. Soc. 2000, 122(22),5411.30 Kawaguchi, Y.; Harada, A. Org. Lett. 2000, 2(10), 1353.31 Iijima, T.; Uemura, T.; Tsuzuku, S.; Komiyama, J. Journal of Polymer Science: Polymer PhysicsEddition 1978, 16, 793.32 Kawaguchi, Y.; Harada, A. J. Am. Chem. Soc. 2000, 122, 3797.33 Harada, A.; Kawaguchi, Y.; Nishiyama, T.; Kamachi, M. Macromol. Rapid Commun. 1997, 18, 535.34 Okada, M.; Kamachi, M.; Harada, A. Macromolecules 1999, 32(21), 7202.35 Amiel, C.; Sebille, B. Advances in Colloid and Interface Science 1999, 79, 105.36 Gosselet, N.; Borie, C.; Amiel, B.; Sebille, B. J. Dispersion Science and Technology 1998, 19(6&7), 805.37 Han, S.; Yoo, M.; Sung, Y.; Lee, Y.; Cho, C. Macromol. Rapid Commun. 1998, 19, 403.


131

Figure 7.8 CPK molecular models of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexylmethacrylate and β-cyclodextrin.

7.4 Conclusions

6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate was successfully

synthesized via a three-stage procedure. Pure side-chain liquid crystalline monomer was

obtained and confirmed through analysis by TLC, 1H and 13C NMR spectroscopy, and

mass spectrometry. This monomer was complexed with MeCD with the goal of

polymerization in aqueous media. However, it was found that even with ratios of MeCD

as high as 3:1 complexation did not alter the water solubility enough to allow for

preparation of aqueous solutions of the complex. The work involving complexation and

polymerization is however in its preliminary stages and future work will involve the

elucidation of some of the factors effecting both the monomer solubility and the

polymerization mechanism. Effort will also be focused on producing a more efficient

synthesis procedure for the side chain liquid crystalline monomer.

Phillip H. Madison, IV Chapter VIII: Recommendations For Future Directions

132

CHAPTER VIII: Recommendations For FutureDirections

The first recommendation would be a direct extension of the current work. In

order to fully comprehend the heterogeneous polymerization mechanism, a study of the

effect of cyclodextrin concentration should be undertaken. The examination of the

effects of cyclodextrin in emulsifier concentrations was an interesting avenue that was

pursued. However, the results of these experiments are preliminary and inconclusive.

Future reactions should be performed in which the levels of cyclodextrin are

systematically altered from 0.0-2.0 equivalents to monomer under similar type

conditions.

An examination of rates could also offer insight into the mechanism involved in

the reactions undertaken in during this project. In fact this was one of the four defining

factors for heterogeneous polymerizations according to Asardy.1 Particle size, and the

initial and final state of reactants are other three factors that can be used to define

heterogeneous polymerizations. Each of these factors should be studied more closely in

order to elucidate the individual mechanism involved in both the cyclodextrin mediated

polymerizations in both water and ethylene glycol, as well as the polymerizations of

monomer using cyclodextrin in emulsifier quantities. In-situ IR and UV spectroscopy

could be interesting methods useful in the elucidation of kinetics. Scanning electron

microscopy and transmission electron microscopy could also be utilized to gain incite

into the final state of the products.

Another question should be answered involves the extent with which prior

complexation effects these polymerizations in terms of mechanism and state of the final

products. It was observed in this work that changes in solvent can effect both the

molecular weights and molecular weight distributions achieved. When the

polymerization media was changed from water to ethylene glycol the result was a

1 Arshady, R. Colloid Polym. Sci. 1992, 270(8), 717.


133

reduction in molecular weight due to chain transfer. It was also found that changing

solvent from water to ethylene glycol resulted in molecular weight distributions that were

systematically lower. If this is a solvent effect as proposed then polymerizations in other

common solvents should also result in similar changes.

They blending of MeCD with methacrylic polymers resulted in optically clear

blends that exhibited interesting thermal properties. It would be interesting to examine

the physical properties of the pure and blended polymers as well in order to determine

how the presence of varying amounts of cyclodextrin affect properties such as tensile

strength, and modulus. Incorporation of nutrients within these blends may also be an

interesting and worthwhile endeavor. It would be interesting to examine how different

concentrations of cyclodextrin within a film would affect the release rate and

bioavailabiltiy of nutrients through the skin. This could ultimately result in novel

methods for the trans-dermal delivery of nutrients, similar to the methods used for the

delivery of drugs like nicotine and Dramamine today.

Complexation of a liquid crystalline monomer for the purpose of polymerization

in a nonsolvent was a novel investigation. More work should be done examining the

effects of complexation with cyclodextrin on the solubility of the monomer. Also, given

that cyclodextrin has been utilized in selective synthesis as a type of steric shield for the

portion of a molecule included within the cyclodextrin cavity,2 it would be interesting to

apply this to polymerizations of multifunctional monomers. Cyclodextrin could be used

to sterically shield one or more reactive sites and lead to preferential reaction of the

unincluded site. The cyclodextrin in many cases is believed to dethread during

polymerization,3 which would leave the second reactive site available for subsequent

polymer modification reactions. For example, a cinnamate-substituted

2 Shiraishi, Y.; Toshima, N.; Kawamura, T.; Mihori, H.; Shirai, H.; Hirai, H. Journal of MolecularCatalysis 1999, 139, 149.3 Jeromin, J.; Noll, O.; Ritter, H. Macromol. Chem. Phys. 1998, 199, 2641.


134

methacrylate (Figure 7.1) has two reactive double bonds. Inclusion within cyclodextrin

has the potential of both protecting the cinnamate double bond; while at the same time

facilitating the solubility of the monomer in water. The multifunctional monomer could

be polymerized in aqueous media while leaving the cinnamate double bond available for

a photocrosslinking reaction for instance.

Figure 8.1 Example of a cinnimate substituted methacrylic monomer for possiblecyclodextrin mediated aqueous polymerization.

O

O (CH2)n O

O

Phillip H. Madison, IV Curriculum Vitae 135


Permanent Address Current Address1689 Rocky Ford Rd. 653 Village Ln., Apt. #3Powhatan, VA 23139 Christiansburg, VA 24073(804) 598-2401 E-mail: [email protected] (540) 552-9204

Objective To obtain an industrial research and development position in the area of polymericmaterials that will utilize my experience and education, while providing theopportunity for growth and advancement.

Education Virginia Polytechnic Institute

and State University King College Blacksburg, VA Bristol, TN Masters of Science in Chemistry Bachelor of Science in Chemistry Expected graduation: June 2001 May 1998 GPA: 3.33/4.00 Major GPA: 3.41/4.00 Research advisor: Dr. Timothy E. Long

Experience8/98-present Virginia Polytechnic Institute Blacksburg, VA

and State University

Graduate Research Assistant/Teaching Assistant/ACS Industrial Short Course Instructor

- Novel carbohydrate mediated synthesis of methacrylic hydrophobic polymers inaqueous media. Characterization techniques employed include TLC, DSC, GPC,1H and 13C NMR, UV, IR, thermogravimetric analysis, mass spectrometry,transmission electron microscopy, and melt rheology.

- Preparation and characterization of novel methacrylic/carbohydrate blends for filmproduction.

- Taught ACS industrial short course laboratories for Polymer Chemistry: Principlesand Practice (8/99, 12/99, 3/00, 8/00,12/00, and 3/01), and Polymer Synthesis:Overview and Recent Developments (6/99, and 6/00).

- Taught polymer synthesis, sophomore organic, and general chemistry laboratories. -----

6/97-12/97 King College Bristol, TN

Undergraduate Research Assistant

- Involved the synthesis of a number of penicillin derivatives, elemental analysis,HPLC, and 1H NMR characterization, and incorporation into bacterial assays todetermine effectiveness as an antibiotic to 12 well-known bacteria.

-----

Phillip H. Madison, IV Curriculum Vitae 136

8/94-5/98 King College Bristol, TN

Undergraduate Teaching Assistant

- Included the setup and supervision of physical, analytical, sophomore organic, andgeneral chemistry laboratories.

-----

94-99 (summers) Holland Builders Inc. Richmond, VA

Carpenter

- Involved in the 2-4 man crew construction of suburban housing. Includingframing, carnishing, and trim work utilizing a variety of power and compressiontools

Presentations & Publications

“Methylated-β-Cyclodextrin Mediated Aqueous Polymerization of Hydrophobic MethacrylicMonomers.” Madison, P. H.; Long, T. E. Biomacromolecules, 2000, 1(4), 615.

“Methylated-β-Cyclodextrin Mediated Aqueous Polymerization of Hydrophobic MethacrylicMonomers.” Madison, P. H.; Long, T. E. Polym. Prepr. (Am. Chem. Soc., Div. Polym.Chem.) fall, 2000.

“Synthesis and Characterization of Poly(1,3-cyclohexadiene) Homopolymers and Star-Shaped Polymers.” David T. Williamson, James F. Elman, Phillip H. Madison, AnthonyJ. Pasquale, and Timothy E. Long Macromolecules; 2001, 34(7), 2108.

“Cyclodextrin Mediated Aqueous Polymerizations of Hydrophobic Monomers.” Madison, P.H.; Long, T. E. Virginia Polytechnic Institute and State University MACRO 2000conference poster session 2000.

“Cyclodextrin Mediated Aqueous Polymerizations of Hydrophobic Monomers.” Madison, P.H.; Long, T. E. Proc. SERMACS 1999.

Thesis Ciclodextrine

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