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 Polytechnic

Institute and State University in partial fulfillment of the
requirements for the degree of
Masters
in
Chemistry
Timothy E. Long
James E. McGrath
Thomas C. Ward
Susan E. Duncan
June 2001
Blacksburg, VA
Keywords: cyclodextrin mediation, aqueous free radical polymerization,

inclusion complexation, carbohydrate/methacrylic blends
Dedication
To my wife, Sarah, who has been there through my time here at VPI &SU and who will
be 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 pursue
something 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 make
the hard times a little easier.
To Mrs. Thomas from Powhatan High and Dr. Simeon Pickard from King College for
igniting, fanning, and sharing both the fire for chemistry that most people don’t
understand, and the ability and desire to share it with those who want to learn.
II
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.
III
Table of Contents
List of Figures..............................................................................................................VI
List of Tables ...............................................................................................................IX
List of Schemes............................................................................................................XI
Abstract ......................................................................................................................... 1
Chapter I: Literature Review ....................................................................................... 3

1.1 Introduction........................................................................................................ 3
1.2 Heterogeneous Free Radical Polymerizations ..................................................... 3
1.2.1 General Concepts of Free Radical Polymerization............................................ 3
1.2.2 Introduction to Heterogeneous Free Radical Polymerizations ......................... 13
1.2.3 Emulsion Polymerization ............................................................................... 14
1.2.4 Suspension Polymerization............................................................................. 17
1.2.5 Dispersion and Precipitation Polymerization .................................................. 19
1.3 Introduction to Cyclodextrins ........................................................................... 20
1.4 Industrial Applications of Cyclodextrins........................................................... 26
1.5 Research Interests Involving Cyclodextrins ...................................................... 30
1.6 Cyclodextrin Mediation of Polymer Synthesis...................................................... 36
Chapter II: Preparation and Characterization of Cyclodextrin/ Methacrylate

Complexes.................................................................................................................... 39
Abstract ..................................................................................................................... 39
2.1 Introduction.......................................................................................................... 40
2.2 Experimental........................................................................................................ 42
2.3 Results and Discussion......................................................................................... 43
2.4 Conclusions.......................................................................................................... 61
Chapter III: Methylated-β β -Cyclodextrin Mediated Aqueous Polymerization of

Hydrophobic Methacrylic Monomers ........................................................................ 63
Abstract ..................................................................................................................... 63
3.1 Introduction.......................................................................................................... 64
3.2 Experimental........................................................................................................ 66
3.4 Conclusions.......................................................................................................... 77
CHAPTER IV: Emulsion Polymerizations Using Cyclodextrin and Linear Dextrin

as Emulsifiers .............................................................................................................. 79
Abstract ..................................................................................................................... 79
4.1.1 Introduction....................................................................................................... 80
4.2 Experimental........................................................................................................ 81
4.4 Conclusions.......................................................................................................... 88
IV
Chapter V: The Preparation and Characterization of Carbohydrate/Methacrylic

Blends .......................................................................................................................... 89
Abstract ..................................................................................................................... 89
5.1 Introduction.......................................................................................................... 90
5.2 Experimental........................................................................................................ 91
5.4 Conclusions.......................................................................................................... 96
CHAPTER VI: Cyclodextrin Mediated Polymerizations in Ethylene Glycol.......... 97

Abstract ..................................................................................................................... 97
6.1 Introduction.......................................................................................................... 98
6.2 Experimental........................................................................................................ 99
6.3 Results and Discussion....................................................................................... 101
6.4 Conclusions........................................................................................................ 109
Chapter VII: Synthesis of a Novel, Side Chain Liquid Crystalline Monomer and
Subsequent Cyclodextrin Mediated Aqueous Polymerization ................................ 111
Abstract ................................................................................................................... 111
7.1 Introduction........................................................................................................ 112
7.2 Experimental...................................................................................................... 115
7.3 Results and Discussion....................................................................................... 117
7.4 Conclusions........................................................................................................ 131
CHAPTER VIII: Recommendations For Future Directions.................................. 132
V
List of Figures
Figure 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 formation
of host-guest complexes with β -CD derivatives.,,,,,,, ................................................. 24
Figure 1.5 Water solubility of β -cyclodextrin (β β -CD), di (DiMe-β β -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 β -cyclodextrin in free and
complexed form...................................................................................................... 45
Figure 2.3. CPK models of cyclohexyl methacrylate and β -cyclodextrin in free and
complexed form...................................................................................................... 45
Figure 2.4 CPK models of 2-ethylhexyl methacrylate and β -cyclodextrin in free and
complexed form...................................................................................................... 45
β -cyclodextrin in chloroform. ......................... 48

Figure 2.5 1H NMR of methylated(1.8)-β
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 the
subsequent 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 the
subsequent 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 subsequent
complex 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 subsequent
complex in chloroform (bottom). ............................................................................ 56
VI
Figure 2.14 Thermogravimetric analysis comparing a CMA/MeCD complex (0.70

mol/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 of
10 ° C/min. .............................................................................................................. 59
Figure 3.1 Thermogravimetric analysis comparing a CMA/ MeCD complex (0.70

mol/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 a
tBuMA/MeCD complex; performed on precipitated product cast from reaction
solution onto a carbon grid...................................................................................... 76
β -CD complex. ....................... 76

Figure 3.4 CPK molecular model of a possible tBuMA/β
Figure 4.1 Chemical structures of several of the more common ionic emulsifiers, and the
structures of MeCD and linear dextrin..................................................................... 83
Figure 6.1 GPC chromatographs of poly(CMA) that was prepared using the complex
before (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
of host-guest complexes with β -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 from

the 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 first
step in the liquid crystalline monomer synthesis scheme. ...................................... 121
VII
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 synthesis
scheme.................................................................................................................. 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)-hexyl

methacrylate. ........................................................................................................ 128
Figure 7.8 CPK molecular models of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl

methacrylate and β -cyclodextrin. .......................................................................... 131
Figure 8.1 Example of a cinnimate substituted methacrylic monomer for possible

cyclodextrin mediated aqueous polymerization. .................................................... 134
VIII
List of Tables
Table Page
Table 1.1 Half-lives (t1/2 = 0.693/kd) of several common free radical thermal initiators at
different temperatures in either benzene or toluene. .................................................. 6
Table 1.2 Physical properties of methylated (1.8)-α α, β , and γ -cyclodextrins as reported by

Wacker Biochem Corporation................................................................................. 25
Table 2.1 Comparison of results from complexation procedures that involved stirring for
either one or six days in chloroform. ....................................................................... 47
either 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 1

mm 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-β β -cyclodextrin or linear
dextrin as surfactants. ............................................................................................. 84
Table 4.2 Results from emulsion type polymerizations incorporating MeCD and linear
dextrin in emulsifier concentrations. ....................................................................... 86

mm 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/MeCD
complex in water and ethylene glycol. .................................................................. 107
Table 6.6 Comparison of the results from the polymerizations of the tBuMA/MeCD
complex in water and ethylene glycol. .................................................................. 107
IX
Table 6.7 Chain transfer constants for methyl methacrylate to various organic solvents.25
............................................................................................................................. 108
X
List of Schemes
Scheme Page
Scheme 1.1 Decomposition reaction of persulfate ion in water. ....................................... 7
β -cyclodextrin complexes .......... 46

Scheme 2.1 Preparation of monomer/methylated(1.8)-β
Scheme 4.1 Preparation of the monomer/MeCD complex (Step 1), and subsequent
aqueous polymerization (Step 2)............................................................................. 70
Scheme 5.1 Bulk polymerizations of tBuMA, CMA, and 2EHMA. ............................... 94
polymerization 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 crystalline
methacrylic monomer/cyclodextrin complex, and subsequent aqueous
polymerization...................................................................................................... 129
XI
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 for
interesting control of reaction parameters. Cyclodextrin mediation of hydrophobic
monomers may offer desirable kinetics over conventional free radical polymerizations,
and it has been shown in this work that cyclodextrin mediation facilitates polymerization
of hydrophobic monomers in aqueous solution and in ethylene glycol. It also may be a
facile method for controlling relative reactivity of comonomer mixtures.1 In addition,
complexation of cyclodextrin with guest molecules has been utilized in selective
synthesis where the host cyclodextrin has been utilized to sterically hinder the attack of
certain reactive sites contained within the host cavity. This aspect of inclusion
complexation could also be utilized in free radical polymerizations of monomers with
multiple reactive double bonds to preferentially reduce the reactivity of the hindered
reactive sites.
This thesis involves the use of methylated (1.8)-β-cyclodextrin (MeCD) as a

mediator for polymerizations in solvents that would not facilitate polymerization of the
pure monomer in the absence of cyclodextrin. This study focuses on the carbohydrate
mediation of a series of methacrylic monomers. t-Butyl methacrylate, n-butyl
methacrylate, cyclohexyl methacrylate, and 2-ethylhexyl methacrylate were complexed
with methylated (1.8)-β-cyclodextrin and subsequently dissolved in either water or
ethylene glycol. The complexes were studied by 1H and 13C NMR spectroscopy, thin
layer chromatography, CPK modeling, and thermogravimetric analysis, and were found
to have molar ratios of cyclodextrin to monomer as high as 1.0 to 0.72. These complexes
were then free radically polymerized in either water or ethylene glycol and resulted in
high molecular weight polymers that precipitated out of solution, allowing for facile
polymer 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 also
recovered and found to be recyclable.
Heterogeneous polymerizations were also performed with 2-ethylhexyl

methacrylate in which linear dextrin and methylated (1.8)-β-cyclodextrin were used in
emulsifier 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 concentrations
between 0.9-3.0 wt%, but remarkably MeCD at 3.0 wt% gave high molecular weight
coagulated polymer with a yield of >90%. It is proposed that a heterogeneous
mechanism inconsistent with the four major types discussed by Arshady2 is taking place.
Unlike typical suspension or emulsion polymerizations, the cyclodextrin mediated
polymerizations are completely homogeneous at the onset, making them more like a
dispersion or precipitation polymerization. However, in dispersion and precipitation
polymerizations the pure monomer is soluble in the reaction media. In the absence of
cyclodextrin, the monomers utilized in this study possessed no appreciable solubility in
the reaction media. Therefore, it is proposed that cyclodextrin acts as a phase transfer
agent, effectively solublizing the hydrophobic monomer and allowing for the aqueous
dispersion or precipitation type polymerization to occur, depending on the relative
solubility of the components.
Bulk polymerizations of t-butyl methacrylate, cyclohexyl methacrylate, and 2-

ethylhexyl methacrylate and their subsequent use in the preparation of
carbohydrate/poly(alkyl methacrylate) blends was also performed in this project. 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. 1H NMR analysis of the polymers from both the cyclodextrin
mediation and bulk polymerizations indicated that the tacticity of the polymers produced
in both cases were identical. The bulk polymers were also used in the preparation of
carbohydrate/methacrylic blends with potential applications in the areas of selective
barriers, biodegradable films. Inclusion of drug molecules or antioxidants into these
cyclodextrin containing films also may have potential in drug delivery, or food packaging
applications.
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 and
confirmed by a combination of mass spectrometry, thin layer chromatography, and 1H
and 13C NMR. This hydrophobic liquid crystalline monomer was subsequently
complexed with 1.0-3.0 equivalents of methylated(1.8)-β-cyclodextrin in an attempt to
alter the water solubility of the monomer. Complexes of this side-chain liquid crystalline
monomer have not been studied previously and it is proposed that complexation with
cyclodextrin will lead not only to novel polymerizations routes for this monomer, but also
to 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, Elsevier
Science, Inc. Tarrytown, NY 1995.
Initiation: I2 2I
X
CH2 C
Y X
I I CH2 C
Y
Propagation:
X
n CH2 C
X Y X X
I CH2 C I CH2 C CH2 C
Y Y Y
n
Termination:
X X X X
I CH2 C CH2 C + C CH2 C CH2 I
Y Y Y Y
n m
combination disproportionation
X X X X X X X X
I CH2 C CH2 C C CH2 C CH2 I I CH2 C CH C HC CH2 C CH2 I
Y Y Y Y Y Y Y Y
n m n m
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 at
different temperatures in either benzene or toluene.4
Half Life at
Initiator
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.
O O O O
O S O O S O H 2O O S O O S OH HO
O O O O
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.
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.
1/2
f kd [I]
R p = kp [M] (4)
kt
From these rate expressions one can derive the kinetic chain length of a polymer. The
kinetic chain length is defined by the following equation:
Rp
ν = (5)
Rt
16
Vogl. O.; Qin, M.; Zilkha, A. Prog. Polym. Sci. 2000, 24(10), 1481.
However, assuming steady state concentration of radicals, kinetic chain length can be
expressed as:
Rp
ν = Ri (6)
or in other terms:
kp [M]
ν= (7)
f kd kt [I] 1/2
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.
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
1 1 [I] [P] [T]

= + CM + CI + CP + CS (11)
Xn Xno [M] [M] [M]
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.
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. ACS
Symp. 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
55
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
68
logarithmic growth in publications and patents 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 and
Cyclodextrins; Proc. of Third Int. Symp. on Clathrate Compounds and Molecular Inclusion and the Second
Int. 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 Academic
Publ.: 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 d
Compostela, 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.
CO2H
NH O NH
(Et)2N O N(Et)2
Acridine Red
Rhodamine B
NH
SO3H HN HO3S
2-(p-toluidino)naphthalene-6-sulfonic acid
8-anilino-1-naphthalenesulfonic acid
F NH2
OH
N HS
O NO2
O
N
H2N S O homocysteine
O
4-aminosulfonyl-7-flouro- OH
2,1,3-benzoxadiazole 4-nitrophenol
(Me)2N N(Me)2
O
(Z)-4,4'-bis(dimethylammoniummethyl)stilbene
OH
HO
2,5 norbornadiene
O
2,6 naphthalenedicarboxylic acid
N
N
O
CO2H O
HN N O
N
O
O
F
Ciprofloxacin Nicardipine NO2
of host-guest complexes with β-CD derivatives.83,84,85,86,87,88,89,90
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 reported

by Wacker Biochem Corporation.93
Methylated(1.8) Cyclodextrin
Property
α β γ
# 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
Average
1120 1310 1500
molecular weight
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, NY
1973 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), and

trimethylated (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
118,119,120,121,122,123,124,125,126,127,128 97 92,129,130
analysis, calorimetry and TGA, X-ray methods,
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. Inclusion
Phenomena 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
144,145,146,147,148,149,150,151
systems. 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 Sciences
2000, 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 Phenomena
1987, 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 Molecular
Catalysis 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 Physics
Eddition 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
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175
Rusa, C.; Tonelli, A. Macromolecules 2000, 33(5), 1813.
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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
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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 Science
1997, 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
Phillip H. Madison, IV Chapter II: Preparation and Characterization of 39
Cyclodextrin/Methacrylate Complexes
Chapter II: Preparation and Characterization of

Cyclodextrin/ 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). 1
H 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.
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
2
1996.
3
4
5
6
7
8
9
10
11
2000, 10(2), 157.
12
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
Catalysis 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 Science
1997, 190, 488.
23
24
25
5411.
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
42 43 44,45
field pulse techniques, volumetric techniques, electron microscopy, 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
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
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. Inclusion
Phenomena 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
50
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.
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
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
52
53
54
Cram, D.; Cram, J. Science 1974, 183(4127), 803.
55
Borman, S. C&EN 2000, 78(31), 31.
Figure 2.2 CPK models of t-butyl methacrylate and β-

cyclodextrin in free and complexed form.
Figure 2.3. CPK models of cyclohexyl methacrylate

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

and β-cyclodextrin in free and complexed form.
OR'
CHCl3
O 24 hrs
O O
O + O 25 oC O
7 R R
R'O OR'
R= or or or
R' = H or Me
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
either 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 two
protons of the monomer at approximately 5.5 and 6.1 ppm were compared to the MeCD proton at 5.0 ppm
1
H 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
Figure 2.5 1H NMR of methylated(1.8)-β-cyclodextrin in chloroform.

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

Figure 2.7 1H NMR of 2-ethylhexyl methacrylate (top), MeCD (middle), and the subsequent complex in chloroform (bottom).
Figure 2.8 1H NMR of cyclohexyl methacrylate in chloroform.

Figure 2.9 1H NMR of cyclohexyl methacrylate (top), MeCD (middle), and the subsequent complex in chloroform (bottom).
Figure 2.10 1H NMR of n-butyl methacrylate in chloroform.

Figure 2.11 1H NMR of n-butyl methacrylate (top), MeCD (middle), and the subsequent complex in chloroform (bottom).
Figure 2.12 1H NMR of t-butyl methacrylate in chloroform.

Figure 2.13 1H NMR of t-butyl methacrylate (top), MeCD (middle), and the subsequent complex in chloroform (bottom).
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
Figure 2.14 Thermogravimetric analysis comparing a CMA/MeCD complex (0.70

mol/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.
110
90
70
Weight (%)
50
30
10
-10
20 40 60 80 100 120 140
Temperature (°C) Universal V3.0G TA Instruments
Figure 2.15 TGA of CMA from 25-150 °C, under N2, at a heating rate of 10 °C/min.
110
90
70
Weight (%)
50
30
10
-10
0 200 400
Figure 2.16 TGA of MeCD from 25-500 °C, under N2, at a heating rate of 10 °C/min.
110
90
70
Weight (%)
50
30
10
-10
0 50 100 150 200 250 300 350 400 450 500
Figure 2.17 TGA of CMA/MeCD complex from 25-500 °C, under N2, at a heating rate
of 10 °C/min.
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
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 62
Polymerizations of Hydrophobic Methcrylic Monomers
Chapter III is reproduced with permission from Madison, P. H.;

Long, T. E. Biomacromolecules 2000, 1(4), 615.
Copyright 2000
American Chemical Society
β -Cyclodextrin Mediated
Chapter III: Methylated-β
Aqueous 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 by
1
H 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.
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.; Santa
Monica, 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.
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.
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
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.
β -Cyclodextrin/Polymer Blends: Poly(tBuMA)/MeCD, poly(2-

Methylated (1.8)-β
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
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.
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
Step #1
OR'
CHCl3
O 24 hrs
O O
O + O 25 C
o O
7 R R
R'O OR'
R= or or or
R' = H or Me
OR'
Step #2
K2S2O8 O
H2O O
O O +
O 7
O 24 hrs O O
R'O OR'
R 50 oC R R
R' = H or Me
aqueous polymerization (Step 2).
Figure 3.1 Thermogravimetric analysis comparing a CMA/ MeCD complex (0.70

mol/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.
Figure 3.2. 1H NMR spectra of CMA, MeCD, CMA/MeCD complex, and poly(CMA) from aqueous polymerization of CMA/MeCD
complex.
either 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 two
protons 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
1
water quantitatively removed the residual cyclodextrin. H 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
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
1
average molecular weight. H 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
1
as 85 % in water with 80-95 % recovery of MeCD in all cases. H 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.
Table 3.2 Polymerizations of t-butyl methacrylate under specified conditions.
Temperature Mna Mw Tgb

Polymer Conditions % Yieldc
(°°C) (g/mol) Mn (°°C)
poly(tBuMA)1 A 50 137,000 3.45 107 77
poly(tBuMA)2 B 50 90,000 3.69 120 85
poly(tBuMA)3 A 60 48,000 3.62 125 65
Table 3.3 Polymerizations of cyclohexyl methacrylate under specified conditions.

(°°C) (g/mol) Mn (°°C)
poly(CMA)1 A 50 142,000 5.91 107 50
poly(CMA)2 B 50 93,000 4.39 110 75
poly(CMA)3 A 60 69,000 6.24 105 72
Table 3.4 Polymerizations of 2-ethylhexyl methacrylate under specified conditions.

(°°C) (g/mol) Mn (°°C)
poly(2EHMA)1 A 50 140,000 3.56 2 74
poly(2EHMA) 2 B 50 56,000 3.20 5 80
poly(2EHMA )3 A 60 53,000 2.75 -8 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), N2
c- 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
.
mm thick films were optically clear as cast from CHCl3 with up to 20 weight % MeCD.
Weight % MeCD Tga (ºC) Weight % MeCD Tga (ºC)

0 118 0 112
5 105 5 100
10 117 10 105
20 124 20 110
Poly(t-butyl methacrylate) Poly(cyclohexyl methacrylate)

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.
Figure 3.3 TEM analysis of precipitate formed from the aqueous polymerization of a
tBuMA/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.
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
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 79
Linear Dextrin as Emulsifiers
CHAPTER IV: Emulsion Polymerizations Using

Cyclodextrin 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.
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.
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.
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
Common Ionic Surfactants:
O O Na
S
O O
Sodium lauryl sulfate

O
S O Na
O
Sodium dodecylbenzene sulfonate
O K
Potassium stearate
O K
Potassium palmitate
Compounds Utilized as Surfactants in This Study:
OR'
OH
O
O O
HO O H
7
R'O OR'
HO OH
n
R' = H or Me
n = 5 by GPCa
Methylated(1.8)-beta-Cyclodextrin Linear Dextrin
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 the
structures of MeCD and linear dextrin.
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 linear

dextrin 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 nitrogen

atmosphere. Time of reaction was varied from 4-24 h.
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.
Table 4.2 Results from emulsion type polymerizations incorporating MeCD and linear
dextrin in emulsifier concentrations.
wt% Emulsifier
Isolated
Monomer Emulsifier compared to H2O Mna
Yieldb
(to monomer)
2-ethylhexyl 0.9
Dextrin >1400 K 24%
methacrylate (2.4)
2-ethylhexyl 3.0
Dextrin 255,000 >90%
methacrylate (8.0)
2-ethylhexyl 0.9
Cyclodextrin 163,000 13%
methacrylate (2.4)
2-ethylhexyl 3.0
Cyclodextrin 474,000 >90%
methacrylate (8.0)
b - Determined gravimetrically after evaporation of solvent and monomers and subtraction of additional,
nonvolatile reaction components
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.
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 of 89
Carbohydrate/Methacrylic Blends
Chapter V: The Preparation and Characterization of

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.
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
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
19
20
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.
β -Cyclodextrin/Polymer Blends: Poly(tBuMA)/MeCD, poly(2-

Methylated (1.8)-β
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-
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; New
York; 1999.
BPO , Bulk
O O
O o O
24 h, 70 C
R R
or or
R=
Scheme 5.1 Bulk polymerizations of tBuMA, CMA, and 2EHMA.

mm thick films were optically clear as cast from CHCl3 with up to 20 weight % MeCD.
Weight % MeCD Tga (ºC) Weight % MeCD Tga (ºC)
0 118 0 112
5 100
5 105
10 105
10 117
20 124 20 110
Poly(t-butyl methacrylate) Poly(cyclohexyl methacrylate)

a - Pyris 1 DSC (2nd heat @ 10 °C/min), N2
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.
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 97
in Ethylene Glycol
CHAPTER VI: Cyclodextrin Mediated

Polymerizations 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 by
1
H 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.
in Ethylene Glycol
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.
in Ethylene Glycol
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.
in Ethylene Glycol
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.
in Ethylene Glycol
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.
in Ethylene Glycol
Step #1
OR'
CHCl3
O 24 hrs
O O
O + O 25 C o O
7 R R
R'O OR'
R= or or or
R' = H or Me
OR'
Step #2
O
Ethylene
Glycol O
O O +
O 7
O K2S2O8 O O R'O OR'
R 50-70 oC, R R
24 hrs
R' = H or Me
polymerization 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.
in Ethylene Glycol
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
1
its elution time. H 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.
in Ethylene Glycol
Table 6.1 Polymerizations of t-butyl methacrylate under specified conditions.

Temperature Mna Mw
Polymer Conditions
(°°C) (g/mol) Mn
poly(tBuMA)1 A 50 56,300 2.59
poly(tBuMA)2 B 50 47,400 2.84
poly(tBuMA)3 A 60 41,300 2.69
Table 6.2 Polymerizations of n-butyl methacrylate under specified conditions.

Temperature Mna Mw
Polymer Conditions
(°°C) (g/mol) Mn
poly(nBuMA)1 A 50 50,100 3.29
poly(nBuMA)2 B 50 59,400 2.65
poly(nBuMA)3 A 60 49,600 2.00
Table 6.3 Polymerizations of cyclohexyl methacrylate under specified conditions.

Temperature Mna Mw
Polymer Conditions
(°°C) (g/mol) Mn
poly(CMA)1 A 50 100,000 2.97
poly(CMA)2 B 50 72,300 4.05
poly(CMA)3 A 60 75,700 2.48
poly(CMA)4 A 70 36,100 4.19
Table 6.4 Polymerizations of 2-ethylhexyl methacrylate under specified conditions.

Temperature Mna Mw
Polymer Conditions
(°°C) (g/mol) Mn
poly(2EHMA)1 A 50 281,000 2.29
poly(2EHMA)2 B 50 194,000 2.26
poly(2EHMA)3 A 60 136,000 2.60
poly(2EHMA)4 A 70 59,000 2.33

a- 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
in Ethylene Glycol
Figure 6.1 GPC chromatographs of poly(CMA) that was prepared using the complex
before (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.
in Ethylene Glycol
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.
in Ethylene Glycol
Table 6.5 Comparison of the results from the polymerizations of the CMA/MeCD
complex in water and ethylene glycol.
Temperature wt% Initiator to Mw

Solvent Mna
(°°C) Monomer 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

Ethylene
50 1.0 100,000 2.97
Glycol
Ethylene
50 9.0 72,000 4.05
Glycol
Ethylene
60 1.0 75,300 2.48
Glycol
Table 6.6 Comparison of the results from the polymerizations of the tBuMA/MeCD
complex in water and ethylene glycol.
Temperature wt% Initiator to Mw

Solvent Mna
(°°C) Monomer 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
Ethylene
50 1.0 56,100 2.59
Glycol
Ethylene
50 9.0 47,900 2.84
Glycol
Ethylene
60 1.0 41,200 2.69
Glycol
in Ethylene Glycol
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 0.394
Butyl Alcohol
80 0.25
60 0.28
Ethylene Glycol
80 0.60
60 0.25
Toluene
80 0.52
60 0.20
Methanol
80 0.33
25
Brandrup, J.; Immergut, E.; Grulke, E. (eds) Polymer Handbook, 4th ed. John Wiley & Sons, Inc.; NY,
1999.
in Ethylene Glycol
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
in Ethylene Glycol
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 111
Monomer for Subsequent MeCD Mediated Aqueous Polymerizations
Chapter VII: Synthesis of a Novel, Side Chain Liquid

Crystalline 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 13
C
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.
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
2
1996.
3
4
5
6
7
8
9
10
11
2000, 10(2), 157.
12
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.
CO2H
NH O NH
(Et)2N O N(Et)2
Acridine Red
Rhodamine B
NH
SO3H HN HO3S
2-(p-toluidino)naphthalene-6-sulfonic acid
8-anilino-1-naphthalenesulfonic acid
F NH2
OH
N HS
O NO2
O
N
H2N S O homocysteine
O
4-aminosulfonyl-7-flouro- OH
2,1,3-benzoxadiazole 4-nitrophenol
(Me)2N N(Me)2
O
(Z)-4,4'-bis(dimethylammoniummethyl)stilbene
OH
HO
2,5 norbornadiene
O
2,6 naphthalenedicarboxylic ac
N
N
O
CO2H O
HN N O
N
O
O
F
Ciprofloxacin Nicardipine NO2
of host-guest complexes with β-CD derivatives.13,14,15,16,17,18,19,20
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 13
C 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. A
1997, 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.
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
1
vacuo at room temperature for 24 h. H 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
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
1
collected by filtration and dreid invacuo at room temperature for 24 h. H 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 13
C 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.

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.
O
O O
O
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)
Step 1
K2CO3(0.5eq)
HO OH KO OH
Reflux in ethanol
78 oC
Added bromohexane (1eq)
in ethanol over 2 h period
Reflux for 24 h
O OH
Step 2 OH O-K +
HO
O
Add bromohexanol
K2CO3 (2.0eq)
(1.08eq) in ethanol over 2h
Reflux in ethanol Reflux for 2 days

O O 78 oC
78 oC
Step 3
OH O
O O
O
THF
N(Et)3, 0 oC
Add methacryloyl chloride in

THF dropwise
O O
Scheme 7.1 Three step synthesis procedure for the liquid crystalline monomer, 6-(4’-
hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate
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
1
isolated yield of monosubstituted product of 36 %. The H 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
1
precipitated into water and the product was filtered off. H 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.
1
H NMR was used to confirm product purity (Figure 7.4) and isolated yield of pure
product was 82 %.
Figure 7.2 1H NMR spectrum of the 4’-hexoxy-biphenyl-4-yloxy hexane byproduct from the first step in the liquid crystalline
monomer synthesis scheme.
Figure 7.3 1H NMR spectrum of the desired product, 4-hexoxy-4’-biphenol from the first step in the liquid crystalline monomer
synthesis scheme.
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.
Phillip H. Madison Chapter VII: Synthesis of a Side Chain Liquid Crystalline 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
1
stored properly at low temperature under nitrogen. H 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

13
and the final product are presented (Figure 7.6). These C 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. John
Wiley & Sons; NY 1991.
Phillip H. Madison Chapter VII: Synthesis of a Side Chain Liquid Crystalline 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.
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 synthesis scheme.
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).
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, and
13
C 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.
Figure 7.7 Electron ionized mass spectrum of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl methacrylate.

n
O O O
O O O
(CH2)6 OR' (CH2)6 (CH2)6
O O O
O
O Complexation H2O
+ 7 Chloroform K2SO4
R'O OR'
R' = H or Me
O O O
(CH2)5 (CH2)5 (CH2)5
CH3 CH3 CH3
Scheme 7.2 Synthesis scheme for the formation of the side-chain liquid crystalline methacrylic monomer/cyclodextrin complex, and
subsequent aqueous polymerization.
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
28
29
5411.
30
31
Iijima, T.; Uemura, T.; Tsuzuku, S.; Komiyama, J. Journal of Polymer Science: Polymer Physics
Eddition 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.
Figure 7.8 CPK molecular models of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl

methacrylate 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 13
C 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 132
For Future Directions
CHAPTER VIII: Recommendations For Future

Directions
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.
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
Catalysis 1999, 139, 149.
3
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.
O (CH2)n O
O O
Figure 8.1 Example of a cinnimate substituted methacrylic monomer for possible
cyclodextrin mediated aqueous polymerization.
Phillip H. Madison, IV Curriculum Vitae 135
Permanent Address Current Address
1689 Rocky Ford Rd. 653 Village Ln., Apt. #3
Powhatan, VA 23139 Christiansburg, VA 24073
(804) 598-2401 E-mail: philmad@yahoo.com (540) 552-9204
Objective To obtain an industrial research and development position in the area of polymeric
materials that will utilize my experience and education, while providing the
opportunity 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
Experience
8/98-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 in
aqueous media. Characterization techniques employed include TLC, DSC, GPC,
1
H and 13C NMR, UV, IR, thermogravimetric analysis, mass spectrometry,
transmission electron microscopy, and melt rheology.
- Preparation and characterization of novel methacrylic/carbohydrate blends for film
production.
- Taught ACS industrial short course laboratories for Polymer Chemistry: Principles
and 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 to
determine 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, and
general chemistry laboratories.
-----
94-99 (summers) Holland Builders Inc. Richmond, VA
Carpenter
- Involved in the 2-4 man crew construction of suburban housing. Including
framing, carnishing, and trim work utilizing a variety of power and compression
tools
Presentations & Publications

“Methylated-β-Cyclodextrin Mediated Aqueous Polymerization of Hydrophobic Methacrylic
Monomers.” Madison, P. H.; Long, T. E. Biomacromolecules, 2000, 1(4), 615.
“Methylated-β-Cyclodextrin Mediated Aqueous Polymerization of Hydrophobic Methacrylic

Monomers.” 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, Anthony
J. 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 2000
conference poster session 2000.
“Cyclodextrin Mediated Aqueous Polymerizations of Hydrophobic Monomers.” Madison, P.

H.; Long, T. E. Proc. SERMACS 1999.

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Carbohydrate Mediation of Aqueous Polymerizations:

Cyclodextrin Mediation of Aqueous Polymerizations of

Thesis submitted to the Faculty of the Virginia Polytechnic

Keywords: cyclodextrin mediation, aqueous free radical polymerization,

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

I lift up my eyes to the hills-

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

Chapter I: Literature Review ....................................................................................... 3

Chapter II: Preparation and Characterization of Cyclodextrin/ Methacrylate

Chapter III: Methylated-β β -Cyclodextrin Mediated Aqueous Polymerization of

CHAPTER IV: Emulsion Polymerizations Using Cyclodextrin and Linear Dextrin

Chapter V: The Preparation and Characterization of Carbohydrate/Methacrylic

CHAPTER VI: Cyclodextrin Mediated Polymerizations in Ethylene Glycol.......... 97

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

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

β -cyclodextrin in chloroform. ......................... 48

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

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

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

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

Figure 2.14 Thermogravimetric analysis comparing a CMA/MeCD complex (0.70

Figure 3.1 Thermogravimetric analysis comparing a CMA/ MeCD complex (0.70

β -CD complex. ....................... 76

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

Figure 7.2 1H NMR spectrum of the 4’-hexoxy-biphenyl-4-yloxy hexane byproduct from

Figure 7.4 1H NMR spectrum of the desired product, 6-(4’-hexoxy-biphenyl-4-yloxy)-

Figure 7.5 1H NMR spectrum of the desired product, 6-(4’-hexyloxy-biphenyl-4-yloxy)-

Figure 7.6 13C NMR spectra of the precursor, 6-(4’-hexoxy-biphenyl-4-yloxy)-hexanol

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

Figure 7.8 CPK molecular models of 6-(4’-hexyloxy-biphenyl-4-yloxy)-hexyl

Figure 8.1 Example of a cinnimate substituted methacrylic monomer for possible

Table 1.2 Physical properties of methylated (1.8)-α α, β , and γ -cyclodextrins as reported by

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 1

Tables 5.3-4 Dependence of Tg on weight % MeCD present in film. Approximately 1

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

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

β -cyclodextrin complexes .......... 46

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

Carbohydrate Mediation of Aqueous Polymerizations:

This thesis involves the use of methylated (1.8)-β-cyclodextrin (MeCD) as a

Heterogeneous polymerizations were also performed with 2-ethylhexyl

Bulk polymerizations of t-butyl methacrylate, cyclohexyl methacrylate, and 2-

In addition, the side chain liquid crystalline monomer, 6-(4’-hexyloxy-biphenyl-4-

Chapter I: Literature Review

Heterogeneous polymerizations are then discussed. The differences between the

1.2 Heterogeneous Free Radical Polymerizations

1.2.1 General Concepts of Free Radical Polymerization

Figure 1.1 General mechanism of free radical polymerization.3

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

Scheme 1.1 Decomposition reaction of persulfate ion in water.3

Rp = kp[M· ][M] (2)

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

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

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

Xn = ν , for disproportionation (8)

where Mo is the molecular weight of the monomer.

Another important factor to consider in free radical polymerization is chain

1 1 [I] [P] [T]