Functionalization of Hyperbranched Polyacrylates

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FUNCTIONALIZATION OF HYPERBRANCHED POLYACRYLATES

BY RADICAL QUENCHING

A Thesis

Presented to

The Graduate Faculty of The University of Akron

In Partial Fulfillment

of the Requirements for the Degree

Master of Science

Zewei Wang

May, 2014

FUNCTIONALIZATION OF HYPERBRANCHED POLYACRYLATES

BY RADICAL QUENCHING

Zewei Wang

Thesis

Approved: Accepted:

Advisor Dean of the College Dr. Coleen Pugh Dr. Stephen Z.D. Cheng

Faculty Reader Dean of the Graduate School Dr. Chrys Wesdemiotis Dr. George R. Newkome

Department Chair Date Dr. Coleen Pugh

ABSTRACT

Hyperbranched polyesters have drawn great attention in many applications, including lubricants, paints, catalyst supports, and drug delivery. Similar to dendrimers, hyperbranched polymers have high branching densities which contribute to higher solubilities and lower viscosities as compared to linear polymers. Furthermore, they have a considerable amount of terminal functional groups throughout their structures, which contribute to their excellent ability to encapsulate molecules and act as a catalyst support.

There are many publications on further grafting on hyperbranched polymers, but few reports on the modification of their end groups. This project concentrates on the synthesis of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) derivatives which will be coupled to the bromine end groups of hyperbranched poly(n-butyl acrylate) by nitroxide radical coupling (NRC). The substituted functional groups include hydroxy, alkene, azido, cyano and nitro groups. TEMPO derivatives are being synthesized from 4-hydroxy TEMPO to form ester or ether by multiple coupling methods such as DCC coupling, mesylation, and alkoxidation. Further nitroxide mediated radical polymerizations may be carried out to modify the behavior of the polymers, mostly by addition of styrenes. The hyperbranched polymers are being synthesized by self-condensing vinyl polymerization (SCVP) of a bromo acrylate inimer.

iii

TABLE OF CONTENTS

Page

LIST OF SCHEMES ...... vi

LIST OF FIGURES ...... viii

LIST OF TABLES ...... x

CHAPTER

Ⅰ. INTRODUCTION ...... 1

1.1 Hyperbranched Polyacrylates ...... 1

1.2 Atom Transfer Radical Polymerization ...... 6

1.3 Atom Transfer Nitroxide Radical Coupling ...... 11

1.4 TEMPO and Its Derivatives ...... 15

1.5 Model Compound for Hyperbranched Polyacrylate...... 18

II. EXPERIMENTS ...... 20

2.1 Materials ...... 20

2.2 Techniques ...... 21

2.3 Synthesis Procedures ...... 22

III. RESULTS AND DISCUSSION ...... 39

3.1 1H and 13C NMR Spectra ...... 39

3.2 Nitroxide Radical Coupling Results ...... 67

IV. CONCLUSION ...... 70

REFERENCES ...... 71

APPENDIX ...... 75

LIST OF SCHEMES

Scheme Page

1.1 Synthesis of Hyperbranched Polyacrylates from Inimers ...... 3

1.2 Synthetic Route of Acrylate Inimer ...... 4

1.3 Use of Hyperbranched MIs for Synthesis of “Hyper-star” Polymers ...... 5

1.4 ATRP Equilibrium ...... 6

1.5 Mechanism of Reverse ATRP ...... 8

1.6 Illustration of SR&NI and AGET ...... 8

1.7 Illustration of ICAR and ARGET ...... 10

1.8 Mechanism of Nitroxide Radical Coupling ...... 12

1.9 Synthetic Mechanism for Poly(GTEMPO-co-EO)-g-PS by Atom Transfer Nitroxide Radical Coupling Chemistry ...... 13

1.10 The Illustration of Two Synthetic Routes for the Comb-like Block Copolymers ...... 13

1.11 Synthetic Route to Functionalized Hyperbranched Polyacrylates ...... 14

1.12 Synthesis of Other Nitroxides form TEMPO-OH ...... 16

1.13 Detailed Synthetic Routes for all TEMPO Derivatives ...... 18

2.1 Synthesis of 2-bromo-3-hydroxypropionic acid ...... 22

2.2 Synthesis of n-butyl 2-bromo-3-hydroxypropionate ...... 23

2.3 Synthesis of n-butyl 3-acetoxy-2-bromopropionate (model compound) ...... 24

2.4 Synthesis of Acrylic Anhydride ...... 25

2.5 Synthesis of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate ...... 25

2.6 Polymerization of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate (standard ATRP) ...... 26

2.7 Polymerization of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate (AGET ATRP) ...... 27

2.8 Synthesis of 2,2,6,6-tetramethyl-[4-yl-(4-methanesulfonate)] piperidine-1-oxyl ...... 28

2.9 Unsuccessful synthesis of 4-acryloxy-2,2,6,6-tetramethylpiperidine-1-oxyl from acrylic acid ...... 29

2.10 Synthesis of 4-acryloxy-2,2,6,6-tetramethylpiperidine-1-oxyl from acryloyl chloride ...... 29

2.11 Unsuccessful synthesis of 4-(3-chloropropionyloxy)- 2,2,6,6-tetramethylpiperidine-1-oxyl ...... 30

2.12 Synthesis of 4-(4-Nitrophenylacetyloxy)- 2,2,6,6-tetramethylpiperidine-1-oxyl ...... 31

2.13 Synthesis of 4-(6-bromohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl .....32

2.14 Synthesis of 4-(6-azidohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl ...... 33

2.15 Synthesis of 4-(6-cyanohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl .....34

2.16 Synthesis of HTEMPO quenched model compound ...... 35

2.17 Synthesis of 4-acryloxy-TEMPO quenched model compound ...... 36

2.18 General procedure of ATNRC ...... 37

vii

LIST OF FIGURES

Figure Page

1.1 Six Different Types of Dendritic Structures ...... 2

1.2 Kinetic Plot (left) and Molecular Weight (lower Right) and Mw/Mn a (upper right) as a Function of Conversion in the CuCl2/TPMA -Mediated b ARGET ATRP of BA , with Variable Hydrazine (N2H4) Reducing Agent ...... 10

1.3 Model Compound for Hyperbranched Polyacrylate ...... 19

3.1 1H NMR spectrum of 2-bromo-3-hydroxypropionic acid ...... 39

3.2 1H NMR spectrum of n-butyl 2-bromo-3-hydroxypropionate ...... 40

3.3 1H NMR spectrum of n-butyl 3-acetoxy-2-bromopropionate ...... 41

3.4 1H NMR spectrum of acrylic anhydride ...... 42

3.5 1H NMR spectrum of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate ...... 43

3.6 13C NMR spectrum of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate ...... 44

3.7 1H NMR spectrum of poly(2-bromo-2-n-butoxycarbonyl)ethyl acrylate ...... 45

3.8 1H and 13C NMR spectrum of 4-mesyl-TEMPO ...... 46

3.9 1H and 13C NMR spectrum of 4-acryloxy-TEMPO synthesized from acryloyl chloride ...... 48

3.10 1H and 13C NMR spectrum of 4-(4-nitrophenylacetyloxy)-TEMPO ...... 50

3.11 1H and 13C NMR spectrum of 4-(6-bromohexanoyloxy)-TEMPO ...... 52

3.12 1H and 13C NMR spectrum of 4-(6-azidohexanoyloxy)-TEMPO ...... 54 viii

3.13 1H and 13C NMR spectrum of 4-(6-cyanohexanoyloxy)-TEMPO ...... 56

3.14 1H NMR spectrum of n-butyl 3-acetoxy-2-HTEPMO- propionate ...... 58

3.15 1H NMR spectrum of n-butyl 3-acetoxy-2-(4-acryloxy-TEMPO)- propionate ...... 60

3.16 1H NMR spectrum of TEMPO-OH functionalized hyperbranched poly(n-butyl)acrylate ...... 61

3.17 1H NMR spectrum of 4-mesyl-TEMPO functionalized hyperbranched poly(n-butyl)acrylate ...... 63

3.18 1H NMR spectrum of 4-acryloxy-TEMPO functionalized hyperbranched poly(n-butyl)acrylate ...... 64

3.19 1H NMR spectrum of 4-(6-azidohexanoyloxy)-TEMPO functionalized hyperbranched poly(n-butyl)acrylate ...... 65

3.20 1H NMR spectrum of 4-(6-cyanohexanoyloxy)-TEMPO functionalized hyperbranched poly(n-butyl)acrylate ...... 66

3.21 GPC Traces of hyperbranched polyacrylate before and after coupling reaction with 4-acryloxy-TEMPO ...... 68

LIST OF TABLES

Table Page 1.1 Experimental Conditions and Properties of PMMA Prepared by Different ATRP Methods ...... 9

1.2 Rate Constant of Radical Quenching ...... 11

1.3 The Data for ATNRC Reaction between methoxyl poly(ethylene oxide)-b-[poly(ethylene oxide-co-2-bromoiso butyryloxy glycidyl ether) (mPEO-b-Poly(EO-co-BiBGE)) and TEMPO-OH (HTEMPO) ...... 14

1.4 Polymer Characterization of PS-Br, PtBA-Br, and Their Corresponding End-Group-Modiﬁed Products ...... 16

2.1 Yields of Nitroxide Radical Coupling of Hyperbranched polyacrylates with TEMPO derivatives ...... 38

3.1 GPC Results of Polymer before and after Coupling...... 67

CHAPTER I

INTRODUCTION

1.1 Hyperbranched Polyacrylates1

Dendritic structures are important in many applications including drug delivery, catalyst support, coatings and, adhesives. In contrast to linear polymers, they have very high branching densities, which leads to higher solubilities in a variety of solvents and lower viscosities than linear polymers. Due to branching, the terminal groups in a dendritic polymer are abundant and well-distributed on the surface of a dendritic micelle, while a perfectly linear chain only has two terminal groups. The terminal groups can be functionalized and give the dendritic polymer a broad range of properties.

There are 6 main types of dendritic architectures: dendrimers, linear-dendritic hybrids, dendrigrafts or dendronized polymers, hyperbranched polymers, multi-arms star polymers, and hypergrafted polymers (Figure 1.1). The first three structures have a degree of branching equal to 1.0, while the last three are random structures. For example, the terminal groups are located throughout the structure of hyperbranched polymers, not just at their surface.

Figure 1.1. Six Different Types of Dendritic Structures1

Of all the dendritic polymers, hyperbranched polymers are the easiest to synthesize and can be produced by one-pot reactions, while the syntheses of the other types of dendritic structures involve multiple steps. Therefore, hyperbranched polymers are more convenient and suitable for industrial applications. Among all of the hyperbranched polymers, hyperbranched polyesters may be the most important because the ester bond in the polymer is degradable, which makes it environmentally friendly. Furthermore, the hyperbranched polyacrylates will degrade into smaller molecules, which may be used for controlled release applications.

There are several synthetic routes to synthesize hyperbranched polyesters. A common method is by condensation polymerizations of ABf (f≥2) monomers. However, condensation polymerizations are usually slow, which is not good for industrial production. Furthermore, the branching in this one-pot polymerization is statistical; therefore, it is less regular than that of an ideal dendrimer and the degree of branching of hyperbranched polymers is generally less than 0.5.2 In order to achieve better properties

(e.g. crosslinking, solubility, ), more terminal groups are needed, which means higher branching densities are needed. In addition to condensation polymerizations, hyperbranched polyesters can be produced as polyacrylates by self-condensing vinyl polymerizations (SCVP) of inimers; inimers contain both an initiating site and a polymerizable monomeric group within the same molecule. Such polymers have broad polydispersities.3

Pugh et al.4 has established a general route to the synthesis of inimers that can be homopolymerized by atom-transfer radical polymerization (ATRP) to produce both hyperbranched polyacrylates that are truly architectural analogues of known linear polyacrylates (Scheme 1.1), as well as new hyperbranched polyacrylates that can be functionalized at each repeat unit with a variety of ester substituents for unique applications.5 Homepolymerization method achieves the highest degree of branching compared to copolymerizations of inimers with standard acrylate monomers.

Scheme 1.1. Synthesis of Hyperbranched Polyacrylates from Inimers4,5

The ideal hyperbranched polyacrylate will have an ester bond between every carbon atom within the polymer backbone and provide a free ester side chain at the same time. Therefore,the key intermediate is a halohydrin in which the halogen atom is α to the

3 ester group, and β to the hydroxyl group; the α-ester weakens the carbon–halogen bond promoting formation of radical and polymerization of the inimer. The synthesis of inimer starts with deaminobromination of D,L-serine via diazotization using sodium nitrite in the presence of HBr and KBr, to generate 2-bromo-3-hydroxypropionic acid with an initiating bromide. This is followed by esterification of the carboxylic acid group, and then esterification of the hydroxy group with acrylic anhydride in the presence of triethylamine to introduce the polymerizable acrylate group (Scheme 1.2).

Scheme 1.2. Synthetic Route of Acrylate Inimer4,5

The bromo acrylate inimer used in this study contains an n-butyl ester substituent. It has a simple structure like the methyl inimer, but is less volatile, and therefore results in more reproducible polymerizations.

The chain end of the hyperbranched polyacrylate polymerized by the above inimer is bromine, which can be further functionalized by different methods. Depending on the functionality that is brought to the polymer, the polymer will have different properties that will be useful in different applications. For example, hydroxy end groups will increase its solubility in aqueous solutions. Amino groups will provide charge in acidic

4 solution, and double bonds will allow further crosslinking. The polymers' thermostability can even be increased by adding a bulky chain end. Because of the high degree of branching, which results in a large amount of functional chain ends throughout the structure, unique properties can be introduced to the polymer. The bromide chain ends also provide the ability for further grafting of linear polymers by radical polymerization, especially atom transfer radical polymerization (ATRP). Gao et al.6 used a hyperbranched polyacrylate as a microinitiator and grafted it with both poly(t-butyl acrylate) (PtBA) and poly[oligo(ethylene glycol) methacrylate] (POEGMA) by ATRP to produce "hyper-star" polymers (Scheme 1.3).

Scheme 1.3. Use of Hyperbranched MIs for Synthesis of “Hyper-star” Polymers6

This functionalization method by grafting to hyperbranched polymer is limited by the types of monomers that are polymerizable by ATRP (e.g. the functional group on the monomer cannot be sensitive to radicals). Instead of grafting, there are other ways to functionalize the bromide chain end. The most convenient method is by a coupling reaction. In ATRP, the halide chain-ends (e.g. Br) can be converted to azides for

Cu(I)-catalyzed azide/alkyne cycloaddition (CuAAC) reactions7, which are the most well known "click reactions". The alkyne can be a functional small molecule or polymer,

5 leading to functional polymers8 and complex structures9. However, in ‘‘click’’ chemistry, the azide group is photosensitive and the alkyne may undergo a Glaser coupling, leading to side reactions. Other methods for chemical modification of activated bromide chain ends include thio-bromo “click” reaction introduced by Percec et al.10 and atom transfer nitroxide radical coupling (ATNRC) reactions by Matyjaszewski11-12and Huang.13-15 Here, we use nitroxide radical coupling as an efficient coupling method to further functionalize the activated bromide chain end of our hyperbranched polyacrylates.

1.2 Atom Transfer Radical Polymerization (ATRP)

ATRP is a controlled radical polymerization that operates by dynamic equilibrium between propagating radicals and dormant species.16 The initiators are alkyl halide species (PnX) and catalysts are transition metal complexes in their lower oxidation state

(Mtm/L). During the reaction, the alkyl-halide bond is broken to generate active radical species (Pn●) and the transition metals go to their higher oxidation state. An equilibrium between the dormant species and the activated species is established during polymerization (Scheme 1.4). Usually, a living radical add monomers at a constant rate of propagation until it is irreversibly terminated by another living radical.17

Scheme 1.4. ATRP Equilibrium17

For copper (Cu) complexes with various ligands, the ATRP equilibrium constants vary over 7 orders of magnitude, and strongly depend on the ligand and the structures of the dormant species.18 The activity of Cu-ligand complexes are generally in the following order: tetradentate (cyclic-bridged) > tetradentate (branched) > tetradentate

(cyclic) > tetradentate (linear) > tridentate > bidentateligands.19 The electron-donating nitrogen atoms in the ligands significantly influence the activity of the Cu complexes, following the order pyridine ≥ aliphatic amine > imine.

As for the dormant species, the activities of alkyl halides follow the order of 3° > 2° >

1°, which is consistent with the carbon-halogen bond dissociation energy. In addition, the radical stability is strengthened by the presence of an α-cyano group, which has a higher activity than either an α-phenyl or an ester group. In the case of halides, the activities follow the order of I > Br >Cl, which are also higher than those of alkyl pseudohalides.18

The polarity of the solvent also has a major influence on the rate of polymerization.

It greatly affects the equilibrium constant of ATRP, due to the polarity difference of Cu(I) and Cu(II) complexes. Cu(I) complexes have low polarity, which makes them unstable in polar solution while Cu(II) complexes are the opposite.20

However, ATRP has many disadvantages. One major problem is oxidation of metal complexes during polymerization by oxygen or other oxidants. ATRP is initiated by R-X activated by metal complexes in their lower oxidation states, which may be easily oxidized. A total inert atmosphere must be maintained during and before polymerization.

As a solution, "reverse" ATRP (Scheme 1.5) was first proposed using the higher oxidation state transition metal complex (X-Mtn+1/L), which is then converted to the lower oxidation state by reaction with a typical free radical initiator or various reducing agents.21 If a traditional ATRP alkyl halide initiator is added to a reverse ATRP system, it is called simultaneous reverse and normal initiation (SR&NI).22 Activators generated by electron transfer (AGET)23 is another ATRP variation. The mechanisms of SR&NI and

AGET ATRP are shown in Scheme 1.6.

Scheme 1.5. Mechanism of Reverse ATRP21

Scheme 1.6. Illustration of SR&NI and AGET22,23

It was demonstrated that a lower amount of catalysts and lower ratio of copper (II) complex versus reducing agent lead to better control of AGET ATRP, as shown in Table

1.1.23

Table 1.1. Experimental Conditions and Properties of PMMA Prepared by Different

a 23 ATRP Methods

Two better approaches of continuously regenerating a small amount of catalyst in

SR&NI and AGET were discovered and named initiators for continuous activator regeneration (ICAR)24 and activator regenerated by electron transfer (ARGET)25

(Scheme 1.7). Reducing agents used in AGET or ARGET include FDA-approved tin(II)

2-ethylhexanoate (Sn(EH)2), glucose, ascorbic acid, phenol, hydrazine, phenylhydrazine, excess inexpensive ligands, nitrogen-containing monomers, and Cu0. The major difference between SR&NI/AGET and ICAR/ARGET is the amount of initiator and reducing agent used. In SR&NI/AGET, equivalent amount of initiating radical or reducing agent is used such that all of the metal complexes are activated in the first place and become oxidized during the reaction. In ICAR/ARGET, excess initiator or reducing agent is used such that the metal complexes are immediately activated once they are

9 oxidized during the reaction, in which situation the metal complexes are always in the lower oxidation states.

Scheme 1.7. Illustration of ICAR and ARGET25

Matyjaszewski et al.23,24 also demonstrated that ARGET ATRP with a reducing agent has the ability to provide well-controlled polymerizations. A linear relationship between ln([M]0/[M]) and time, and the linear increase in molecular weight with conversion shown in Figure 1.2 demonstrate that termination and chain transfer, respectively, are not detectable.

Figure 1.2. Kinetic plot (left) and molecular weight (lower Right) and Mw/Mn (upper

a b right) as a function of conversion in the CuCl2/TPMA -mediated ARGET ATRP of BA , with variable hydrazine reducing agent. [BA]0/[EtBrIB]0/[CuCl2]0/[TPMA]0/[N2H4]0 =

200/1.28/0.01/0.1/0.05 or 0.1; [BA]0 = 5.88 M; 60 °C; 20% anisole by volume. a: tris(2-pyridylmethyl)amine; b: butyl acrylate.24

1.3 Atom Transfer Nitroxide Radical Coupling

Nitroxides are the key ingredient in this coupling reaction which has a stable radical.

A well-known application of nitroxides is to quench and identify radicals. This leads to the use of nitroxide in determining the initiating efficiency in radical polymerizations.

Furthermore, nitroxides are commonly used to study the kinetics of reactions involving the formation of radicals.26 These techniques are based on the fact that the free radical are quenched by nitroxides at diffusion-controlled rates. Take (2,2,6,6-tetramethylpiperidin

-1-yl)oxyl (TEMPO), which is the most widely used nitroxide, as an example; the rate constants of radical quenching between TEMPO and carbon-centered radicals are shown in Table1.227. All carbon-centered radicals are quenched by TEMPO at close to 109 M-1 s-1. Therefore, this kind of radical quenching can be assumed to happen instantaneously, such that the rate of reaction is mainly controlled by diffusion.

Table 1.2. Rate Constant of Quenching between Carbon-centered Radicals and TEMPO 27

Radical type Rate constant of radical quenching

Primary radicals 1.2×109 M-1 s-1

Secondary radicals 1.0×109 M-1 s-1

Tertiaty radicals 0.8×109 M-1 s-1

Benzyl radicals 0.5×109 M-1 s-1

Based on the previous studies of nitroxide radical quenching, a new coupling method was established using the nitroxide radical coupling, which is very efficient at functionalizing polymers with halogenated chain ends that are activated toward radical formation.28 After activation by Cu(I), the halogenated chain end will generate a free radical that is rapidly quenched by a nitroxide radical (Scheme 1.8). This is an atom-efficient reaction, which means that there are no side reactions. The functional groups are pre-attached to the nitroxide radical, and therefore are not involved in the polymerization. Ideally, any functional group can be coupled to the polymer chain ends.

Scheme 1.8. Mechanism of Nitroxide Radical Coupling

Atom transfer nitroxide radical coupling (ATNRC) has proven to be one of the most efficient grafting methods. Huang et al. successfully synthesized a wide range of block copolymers by ATNRC. For example, Scheme 1.9 shows the ATNRC they used for grafting polystyrene (PS) side chains into poly(ethylene oxide) (PEO) backbone. The efficiency of the nitroxide coupling reaction was found to be over 90% when the molecular weights of PS and PEO were not high.29

Scheme 1.9. Synthetic Mechanism for Poly(GTEMPO-co-EO)-g-PS by Atom Transfer

Nitroxide Radical Coupling Chemistry29

They also found that the highest efficiency (over 90%) was achieved by using the combination of Cu(0)/ Cu(I) as reductant at temperatures from 25 to 75 °C, which are similar to typical ATRP conditions. At higher temperatures, the alkoxyamine bond could be cleaved, decreasing the efficiency.30

However, when the halogen group was present in the repeat unit of the backbone polymer, steric hindrance decreases the coupling efficiency. As a consequence, one solution Huang found was to add several styrene units between the backbone and side chain to create more space. By adding extra styrene during the ATNRC, the coupling efficiency was increased by 60% as demonstrated by Table 1.3.31

Scheme 1.10. The illustration of two synthetic routes for the comb-like block

copolymers.31

Table 1.3. The Data for ATNRC Reaction between methoxyl poly(ethylene

oxide)-b-[poly(ethylene oxide-co-2-bromoiso butyryloxy glycidyl ether)

(mPEO-b-Poly(EO-co-BiBGE)) and TEMPO-OH (HTEMPO) 31

The goal of this research is to synthesize functionalize hyperbranched polyacrylates by quenching the radicals generated from the bromine chain ends with TEMPO derivatives as shown in Scheme 1.11.

Scheme 1.11. Synthetic Route to Functionalized Hyperbranched Polyacrylates.

1.4 TEMPO and Its Derivatives

TEMPO and its derivatives are stable radicals that can be used in diverse reactions.

The TEMPO reactions are divided into nitroxide-mediated radical polymerizations

(NMRP), nitroxide radical couplings (NRC) and redox reactions.

To indroduce other functional groups to the polymer, these functional groups can be attached to TEMPO. We are using 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl

(TEMPO-OH), which has a hydroxy group to attach other functional groups. The hydroxy group is very reactive, and can be reacted to form ether or ester through nucleophilic substitution and condensation reactions, respectively.

Monteiro et al.28 established efficient routes to synthesize many TEMPO derivatives from TEMPO-OH (Scheme 1.12). Puriﬁcation of the resulting compounds by column chromatography is convenient due to the bright orange color of the products and their very different polarities from the starting TEMPO-OH. The range of nitroxides that were synthesized include glycidyl ether, styryl, acrylate, methacrylate, alkyne, dialkyne, tosylate, active ester, biotin, and pyrene-containing TEMPO. They also conducted the nitroxide radical coupling reaction of these TEMPO derivatives with linear polystyrene and poly(t-butyl)acrylate synthesized by ATRP. The conversion of these reactions were all above 90% (Table 1.4).

Scheme 1.12. Synthesis of Other Nitroxides form TEMPO-OH28

Table 1.4. Polymer Characterization of PS-Br, PtBA-Br, and Their Corresponding

End-Group-Modiﬁed Products28

Liang et al.32 also established an efficient way to introduce many functionalities to

TEMPO-OH by coupling with carboxylic acid derivatives using

N,N'-dicyclohexylcarbodiimide (DCC).33 However, limitations were observed due to the type of carboxylic acid that can successfully couple with TEMPO-OH. (Details explained in results and discussion section.) Subsequently, it was concluded that this wasn't a universal method for generating all TEMPO derivatives.

These nitroxides are usually characterized by electrospray ionization-mass spectroscopy (ESI-MS), electron spin resonance (ESR) spectroscopy, and elemental analysis. NMR spectroscopy cannot identify a free radical without quenching it first, such as with phenyl hydrazine, because the vibration of free radical will interfere and broaden the other resonances. If the nitroxide contains aromatic structures, pentafluorophenyl hydrazine is used.

The detailed reactions used to functionalize the starting TEMPO-OH are illustrated in Scheme 1.13, including condensation, coupling reaction and subsequent nucleophilic substitutions.

Scheme 1.13. Detailed Synthetic Routes for all TEMPO Derivatives

1.5 Model Compound for Hyperbranched Polyacrylate

Before carrying out nitroxide radical coupling reactions on the hyperbranched polyacrylates, we first tested the reaction on model compound (Figure 1.3) to identify possible side reactions and to check the efficiency of the coupling reaction. The

18 efficiency of coupling may vary with TEMPO derivatives.

Figure 1.3. Model Compound for Hyperbranched Polyacrylate

CHAPTER II

EXPERIMENTS

2.1 Materials

Acetyl chloride (Acros, 98%), acrylic acid (Acros, 99.5%), acryloyl chloride

(Aldrich, 97%), n-butanol (Alfa Aesar, ACS, 99.4%), butyl acrylate (Aldrich, 99%),

3-chloropropionic acid (Alfa Aesar, 98%), cupric bromide (Aldrich, 99%), D,L-serine

(Sigma, 98%), 4-dimethylaminopyridine (Aldrich, 99%), ethyl 2-bromoisobutyrate

(Aldrich, 98%), hydrogen bromide (Sigma-Aldrich, 48%), 4-hydroxy-2,2,6,6- tetramethylpiperidin-1-oxyl (Oakwood, 98%), L-ascorbic acid (Fisher, 99%), methanesulfonyl chloride (Acros, 99.5%), 4-nitrophenylacetic acid (Aldrich, 99%),

N,N'-dicyclohexylcarbodiimide (Aldrich, 99%), pentafluorophenyl hydrazine (Alfa Aesar,

97%), pentamethyldiethylenetriamine (Aldrich, 99%), phenyl hydrazine (Alfa Aesar,

97%), potassium bromide (Artcraft), pyridine (EMD, 99%), sodium azide (EMD, 99%), sodium cyanide (Aldrich, 97%), and sodium nitrite (Alfa Aesar, 98%) were used as received. Acetonitrile was dried by distilling it from CaH2. Cuprous bromide (Alfa Aesar,

99%) was purified by sequentially washing it with acetic acid and ethanol.

Dichloromethane was dried by distilling it from CaH2. Ethyl ether was dried by distilling it from Na/benzophenone. Triethylamine (Sigma-Aldrich, 99%) was dried by distilling it 20 from KOH.

2.2 Techniques

2.2.1 NMR

1H (300 MHz) and 13C (75 MHz) NMR spectra (δ, ppm) were recorded on a Varian

Mercury 300 spectrometer. All spectra were recorded in CDCl3 unless mentioned otherwise, and the resonances were measured relative to the residual solvent resonances and referenced to tetramethylsilane.

One mole equivalent of phenyl hydrazine was added to the nitroxide compounds before their 1H NMR spectra were recorded.

2.2.2 Degassing solutions by freeze-pump-thaw(F-P-T) cycles

The Schlenk tube/flask was frozen in liquid nitrogen for 5 min, then a vacuum (1 mm Hg)was applied for 15 min. After that the Schlenk tube/flask was closed to vacuum and immersed in a beaker with methanol at room temperature to thaw for 5 min. This process was repeated until no decavitation bubbles were observed after thawing.

2.2.3 Schlenk line

All reactions were performed under a N2 atmosphere using a Schlenk line unless noted otherwise.

2.2.4 TLC

Thin-layer chromatography (TLC) was performed using silica gel plates (Sorbent

Technologies, 200 μm particle size w/UV254) with polyester backing.

2.2.5 GPC

Number-average (Mn) and weight-average (Mw) molecular weights relative to linear polystyrene (GPCPSt) and polydispersities (PDI=Mw/Mn) were determined by gel permeation chromatography (GPC) from calibration curves of log Mn vs elution volume at 35 °C using THF (unless noted otherwise) as solvent (1.0 mL/min), a guard column and a set of 50 Å, 100 Å, and two 104 Å, Styragel 5 μm columns, a Waters 486 tunable

UV/vis detector set at 254 nm, a Waters 410 differential refractometer, and Millenium

Empower 2 software. The samples (∼0.1 g/L) were dissolved overnight and filtered through a 0.45 μm PTFE filter before injection.

2.3 Synthesis Procedures

2.3.1 Synthesis of hyperbranched polyacrylate and its model compound.

Scheme 2.1 Synthesis of 2-bromo-3-hydroxypropionic acid4

NaNO2 (68.7 g, 1.00 mol) was added batchwise over 6 h to a cooled (-10 °C) solution of D,L-serine (54.0 g, 0.51 mol), potassium bromide (206 g, 1.89 mol), and

22 hydrobromic acid (209 g, 48 wt%, 1.23 mol) in distilled water (400 mL) that had been sparged with N2 for 10 min; the solution turned light green upon addition of NaNO2. The solution was stirred at room temperature for 20 h. It was then salted out with NaCl and extracted five times with ethyl acetate (100 mL ea). The organic layers were combined and dried over MgSO4. After filtration and removing the solvent by rotary evaporation, followed by drying under vacuum on a Schlenk line, the resulting yellow solid was recrystallized from CH2Cl2 to yield 41.1 g (47.4%) of 2-bromo-3-hydroxypropionic acid as a white crystalline solid. 1H NMR: d = 4.03 (dd, CHHOH, 2J = 11.5 Hz, 3J = 5.2 Hz),

4.05 (dd, CHHOH, 2J = 11.7 Hz, 3J = 7.2 Hz), 4.41 (dd, CHBr, 3J = 7 Hz, 3J = 5.3 Hz).

Scheme 2.2 Synthesis of n-butyl 2-bromo-3-hydroxypropionate34

Concentrated hydrobromic acid (0.51 g, 48 wt%, 3.0 mmol) was added all at once to a solution of 2-bromo-3-hydroxypropionic acid (19 g, 0.11 mol) in n-butanol (71 mL,

0.78 mol). After stirring the solution at reflux for 24 h, the solvent was distilled under vacuum at 45 °C. The resulting yellow liquid was washed twice with aq NaHCO3 (50 mL ea) and once with brine (100 mL). The organic layer was dried over Na2SO4. After filtration, the solvent was removed by rotary evaporation, and the residue was dried under vacuum to yield 20.5 g (81.8%) of n-butyl 2-bromo-3-hydroxypropionate as a colorless

1 3 3 oil. H NMR: d = 0.96 (t, CH2CH3, J = 7.3), 1.42 (sext, CH2CH3, J = 7.5 Hz), 1.68 (pent,

3 3 2 3 CH2CH2CH3, J = 7.2 Hz), 2.49 (t, OH, J = 7 Hz), 3.94 (ddd, CHHOH, J = 12.0 Hz, J =

5.7 Hz, 3J = 7 Hz), 4.05 (ddd, CHHOH, 2J = 12.1 Hz, 3J = 7.4 Hz, 3J = 7 Hz), 4.22 (dt,

3 5 3 3 OCH2CH2, J = 6.5 Hz, J = 4.5 Hz), 4.35 (dd, CHBr, J = 7.3 Hz, J = 5.6 Hz).

Scheme 2.3 Synthesis of n-butyl 3-acetoxy-2-bromopropionate

(model compound)

A solution of acetyl chloride (1.94 g, 24.1 mmol) in dry ether (5 mL) was added dropwise over 70 min to an ice-cooled solution of n-butyl 2-bromo-3-hydroxypropionate

(4.63 g, 17.6 mmol) and triethylamine (2.24 g, 22.2 mmol) in dry ether (15 mL). A white precipitate formed upon addition. The reaction was then warmed to room temperature and stirred for 16 h, then poured into ice water (150 mL) and extracted four times with ether

(50 mL ea). The organic layers were combined and dried over MgSO4. After filtration, the solvent was removed by rotary evaporation, and the yellow residue was purified by flash column chromatography using silica gel as the stationary phase and CH2Cl2 as the eluant to yield 3.54 g (64.5%) of n-butyl 3-acetoxy-2-bromopropionate as a light yellow oil. 1H

3 3 NMR: 0.94 (t, CH2CH3, J = 7.3), 1.41 (sext, CH2CH3, J = 7.5 Hz), 1.66 (pent,

3 3 5 CH2CH2CH3, J = 7.0 Hz), 2.07 (s, COCH3), 4.20 (td, OCH2CH2, J = 6.6 Hz, J = 2 Hz),

4.39 (dd, CHCHHO, 2J = 11.5 Hz, 3J = 5.6 Hz), 4.46 (dd, CHBr, 3J = 8.1 Hz, 3J = 5.8 Hz),

4.48 (dd, CHCHHO, 2J = 11.5 Hz, 3J = 8.1 Hz).

Scheme 2.4 Synthesis of Acrylic Anhydride

A solution of acryloyl chloride (2.70 g, 29.8 mmol) in dry THF (50 mL) and a solution of triethylamine (2.81 g, 27.7 mmol) in dry THF (25 mL) was added dropwise simultaneously over 30 min to a solution of acrylic acid (2.00 g, 27.8 mmol) in dry THF

(100 mL) at 0 °C. The reaction was stirred at RT for 23 h. After filtration, the solvent was removed by rotary evaporation. The residue was dissolved in CH2Cl2 (50 mL), and washed twice with 1% aq. NaHCO3 (25 mL each) and once with saturated aq. NaCl (50 mL), dried over Na2SO4. After filtration, the solvent was removed by rotary evaporation.

The yellow residue was distilled (33 °C/ 2 mm Hg) to yield 2.37 g (67.7%) of acrylic

1 3 2 anhydride as a colorless liquid. H NMR: 6.07 (dd, CHHb= trans to CO, J = 10.0 Hz, J =

3 3 3 1.2 Hz), 6.19 (dd, =CHCO, J = 16.8 Hz, J = 10.0 Hz), 6.56 (dd, CHaH= cis to CO, J =

16.8 Hz, 2J = 1.3 Hz).

Scheme 2.5 Synthesis of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate34

A solution of acrylic anhydride (0.854 g, 6.77 mmol) in THF (10 mL) was added dropwise over 10 min to a solution of n-butyl 2-bromo-3-hydroxypropionate (1.01 g, 4.49

25 mmol) and triethylamine (0.725 g, 7.17 mmol) in THF (25 mL) at 0 °C. After stirring at

RT for 21 h, the light yellow solution was poured into ice water (25 mL) and stirred for

0.5 h. THF was removed by rotary evaporation. The residue was extracted twice with

CH2Cl2 (25 mL each). The organic layers were combined and washed twice with 1% aq.

NaHCO3 (25 mL each), once with saturated aq. NaCl (25 mL), and dried over Na2SO4.

After filtration, the solvent was removed by rotary evaporation. The yellow oil residue was purified by column chromatography (Rf = 0.4) using silica gel as the stationary phase and Hexanes/EtOAc (2:1 v/v) as the eluant to yield 0.810 g (64.7%) of

(2-bromo-2-n-butoxycarbonyl)ethyl acrylate as an colorless oil. 1H NMR: 0.93 (t,

3 3 3 CH2CH3, J = 7.3), 1.39 (sextet, CH2CH3, J = 7.3 Hz), 1.65 (quin, CH2CH2CH3, J = 6.9

3 5 2 3 Hz), 4.21 (td, OCH2CH2, J = 6.6 Hz, J = 2 Hz), 4.43 (dd, CHCHHO, J = 11.5 Hz, J =

5.6 Hz), 4.55 (dd, CHBr, 3J = 8.1 Hz, 3J = 5.8 Hz), 4.56 (dd, CHCHHO, 2J = 11.5 Hz, 3J =

3 2 3 8.1 Hz), 5.89 (dd, CHHb= trans to CO, J = 10.5 Hz, J = 1.5 Hz), 6.11 (dd, =CHCO, J =

3 3 2 17.3 Hz, J = 10.5 Hz), 6.44 (dd, CHaH= cis to CO, J = 17.3 Hz, J = 1.5 Hz).

Scheme 2.6 Polymerization of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate

(standard ATRP)

In a typical procedure, a solution of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate

(0.402 g, 1.44 mmol) in CH3CN (0.25 mL) was added under N2 to a degassed (3 cycles of

F-P-T) mixture of CuBr (2.2 mg, 15 μmol) and PMDETA (20 μL, 96 μmol) in CH3CN

(0.25 mL) in a dry high vacuum flask. The inimer mixture was degassed by 3 F-P-T cycles and stirred at 80 °C under vacuum for 43 h. Then the polymerization was quenched by immersing the high vacuum flask into liquid N2. The contents of the polymerization flask were thawed, exposed to the atmosphere, diluted with 10 mL THF and passed through basic alumina. After removing the solvent by rotary evaporation,

0.304 g (75.6%) of mixture of polymer and inimer was obtained as colorless liquid; conversion=20% (determined by 1H NMR of crude product using vinyl resonances at

3 5.8-6.5 ppm and methyl resonance at 0.96 ppm); Mn = 8.1×10 g/mol, PDI= 1.38.

Scheme 2.7 Polymerization of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate (AGET

ATRP)

In a typical procedure, (2-bromo-2-n-butoxycarbonyl)ethyl acrylate (2.00 g, 7.17 mmol) was added to a mixture of CuBr (17.0 mg, 76 μmol) and PMDETA (15 mg, 87

μmol) in CH3CN (2.5 mL) in a dry high vacuum flask. The inimer mixture was degassed by 3 F-P-T cycles and L-Ascorbic Acid (15.6 mg, 89 μmol) was added to the flask under a flow of nitrogen. The polymerization was stirred at 80 °C under vacuum for 63 h and then quenched by immersing the high vacuum flask into liquid N2. The contents of the polymerization flask were thawed, exposed to the atmosphere, diluted with 30 mL THF

27 and passed through basic alumina. After concentrating the solution using rotary evaporation, the residue was precipitated into THF/Hexanes (1/30 v/v) (30 mL). The solvent was decanted and the precipitate was washed 3 times with cold Hexanes (5 mL each) to yield 0.449 g (22.4%) of hyperbranched poly(2-bromo-2-n-butoxycarbonyl)ethyl acrylate as a colorless gummy solid; conversion=39% (determined by 1H NMR of crude product using vinyl resonances at 5.8-6.5 ppm and methyl resonance at 0.96 ppm); Mn =

12.5×103 g/mol, PDI= 6.50.

2.3.2 Synthesis of HTEMPO derivatives

Scheme 2.8 Synthesis of

2,2,6,6-tetramethyl-[4-yl-(4-methanesulfonate)]piperidine-1-oxyl

Methanesulfonyl chloride (0.181 g, 1.58 mmol) was added dropwise over 15 min to solution of TEMPO-OH (0.199 g, 1.16 mmol) in pyridine (2.5 mL). The reaction was stirred at RT for 18 h. The resulting orange solution was diluted with CH2Cl2 (5 mL) and washed sequentially with 1 M aq. HCl (10 mL), saturated aq. NaHCO3 (10 mL), and brine (10 mL). The organic layer was dried over Na2SO4. After filtration, the solvent was removed by rotary evaporation. The orange solid residue was recrystallized from 10 mL of Hexanes/CH2Cl2 (9:1 v/v) to yield 0.157 g (54.3%) of

2,2,6,6-tetramethyl-[4-yl-(4-methanesulfonate)]piperidine-1-oxyl as an orange crystalline

1 4 solid; mp: 92-93 °C . H NMR: 1.24 (d, CH3 of TEMPO, J = 11.1 Hz), 1.8 (dd, CHH of

TEMPO, 2J = 11.7 Hz, 3J = 11.7 Hz), 2.09 (dd, CHH of TEMPO, 2J = 12.8 Hz, 3J = 4.4

3 3 Hz), 3.01 (s, OSO2CH3), 4.95 (tt, CH of TEMPO, J = 11.4 Hz, J = 4.3 Hz).

Scheme 2.9 Unsuccessful synthesis of

4-acryloxy-2,2,6,6-tetramethylpiperidine-1-oxyl from acrylic acid

A solution of acrylic acid (0.112 g, 1.56 mmol) in dry ether (5 mL) was added dropwise over 15 min to a solution of TEMPO-OH (0.209 g, 1.21 mmol), DMAP (16 mg,

0.13 mmol) and DCC (0.250 g, 1.21 mmol) in dry ether (15 mL). The reaction was stirred at RT for 25 h. A white precipitate formed upon addition. The solution was filtered through celite. After the solvent was removed from the filtrate by rotary evaporation, the residue was purified by column chromatography (Rf = 0.6) using silica gel as the stationary phase and Hexanes/EtOAc (7:3 v/v) as the eluant to yield 32.3 mg (11.8%) of

4-acryloxy-2,2,6,6-tetramethylpiperidine-1-oxyl as an orange solid with a large amount of side product.

Scheme 2.10 Synthesis of 4-acryloxy-2,2,6,6-tetramethylpiperidine-1-oxyl from

acryloyl chloride27

A solution of acryloyl chloride (0.116 g, 1.28 mmol) in dry ether (5 mL) was added dropwise over 15 min to an ice-cooled solution of TEMPO-OH (0.201 g, 1.17 mmol) and triethylamine (0.127 g, 1.26 mmol) in dry ether (15 mL). A white precipitate formed during addition. The reaction was then stirred at room temperature for 16 h. After filtration, the solvent was removed from the filtrate by rotary evaporation, and the yellow residue was purified by column chromatography (Rf = 0.8) using silica gel as the stationary phase and Hexanes/EtOAc (2:1 v/v) as the eluant to yield 0.109 g (41.1%) of

4-acryloxy-2,2,6,6-tetramethylpiperidine-1-oxyl as an orange solid; mp: 102 °C . 1H NMR:

4 2 3 1.25 (d, CH3 of TEMPO, J = 5.6 Hz), 1.69 (dd, CHH of TEMPO, J = 11.7 Hz, J = 11.7

Hz), 1,98 (dd, CHH of TEMPO, 2J = 12.7 Hz, 3J = 4.3 Hz), 5.15 (tt, CH of TEMPO, 3J =

3 3 2 11.3 Hz, J = 4.4 Hz), 5.82 (dd, CHHb= trans to CO, J= 10.2 Hz, J = 1.5 Hz), 6.10 (dd,

3 3 3 2 =CHCO, J = 17.3 Hz, J = 10.2 Hz), 6.40 (dd, CHaH= cis to CO, J = 17.3 Hz, J = 1.5

Hz).

Scheme 2.11 Unsuccessful synthesis of

4-(3-chloropropionyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl

A solution of 3-chloropropionic acid (0.133 g, 1.23 mmol) in dry ether (5 mL) was added dropwise over 15 min to a solution of TEMPO-OH (0.204 g, 1.18 mmol), DMAP

(15 mg, 0.12 mmol) and DCC (0.239 g, 1.16 mmol) in dry ether (20 mL). The reaction was stirred at RT for 27 h. A white precipitate formed upon addition. The reaction was filtered through celite. After the solvent was removed from the filtrate by rotary evaporation, the residue was purified by column chromatography (Rf = 0.4-0.5) using silica gel as the stationary phase and Hexanes/EtOAc (2:1 v/v) as the eluant to yield less than 10 mg of 4-(3-chloropropionyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl with large amount of side product.

Scheme 2.12 Synthesis of

4-(4-Nitrophenylacetyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl

A solution of 4-nitrophenylacetic acid (0.219 g, 1.21 mmol) in dry ether (5 mL) was added dropwise over 15 min to a solution of TEMPO-OH (0.200 g, 1.16 mmol), DMAP

(15 mg, 0.13 mmol) and DCC (0.242 g, 1.17 mmol) in dry ether (15 mL). The reaction was stirred at RT for 22 h. A yellow precipitate formed upon addition. The reaction was filtered through celite. After the solvent was removed from the filtrate by rotary evaporation, the residue was purified by column chromatography (Rf = 0.67) using silica

31 gel as the stationary phase and Hexanes/EtOAc (2:1 v/v) as the eluant and recrystallized from 17 mL of Hexanes/EtOAc (15:2 v/v) to yield 0.214 g (54.8%) of

4-(4-nitrophenylacetyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl as an orange crystalline

1 4 solid; mp: 85-86 °C . H NMR: 1.19 (d, CH3 of TEMPO, J = 5.6 Hz), 1.57 (dd, CHH of

TEMPO, 2J = 11.7 Hz, 3J = 11.7 Hz), 1,89 (dd, CHH of TEMPO, 2J = 12.5 Hz, 3J = 4.0

3 3 Hz), 3.70 (s, COCH2), 5.06 (tt, CH of TEMPO, J = 11.4 Hz, J = 4.3 Hz), 7.45 (d, CH ortho to CCH2, J = 8.5 Hz), 8.19 (d, CH ortho to CNO2, J = 8.5 Hz).

Scheme 2.13 Synthesis of

4-(6-bromohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl

A solution of 6-bromohexanoic acid (0.228 g, 1.17 mmol) in dry CH2Cl2 (5 mL) was added dropwise over 10 min to a solution of TEMPO-OH (0.201 g, 1.17 mmol), DMAP

(17 mg, 0.14 mmol) and DCC (0.238 g, 1.15 mmol) in dry CH2Cl2 (15 mL). The reaction was stirred at RT for 27 h. A yellow precipitate formed upon addition. The reaction was filtered through celite. After the solvent was removed from the filtrate by rotary evaporation, the residue was purified by column chromatography (Rf = 0.95) using silica gel as the stationary phase and Hexanes/EtOAc (2:1 v/v) as the eluant to yield 0.343 g

(83.9%) of 4-(6-bromohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl as an orange

1 4 oil. H NMR: 1.24 (d, CH3 of TEMPO, J = 2.9), 1.4-2.0 (m, CH2 of TEMPO and

3 3 COCH2(CH2)3CH2Br), 2.30 (t, COCH2, J = 7.2 Hz), 3.41 (t, CH2Br, J = 6.74 Hz), 4.98

(tt, CH of TEMPO, 3J = 11.4 Hz, 3J = 4.3 Hz).

Scheme 2.14 Synthesis of

4-(6-azidohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl

NaN3 (77.7 mg, 1.20 mmol) was added all at once to a solution of

4-(6-bromohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl (0.3912 g, 1.12 mmol) in

DMF (20 mL) and stirred at RT for 25 h. After reaction, the solution was diluted with

H2O (25 mL) and extracted 3 times with Et2O (25 mL each). The organic layers were combined, washed 3 times with H2O (20 mL each) and dried with MgSO4. After the solvent was removed from the filtrate by rotary evaporation, the residue was dried under vacuum to yield 0.309 g (88.6%) of

4-(6-azidohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl as an orange oil. 1H NMR:

4 1.23 (d, CH3 of TEMPO, J = 4.1), 1.3-1.7 (m, CHH of TEMPO and

2 3 COCH2(CH2)3CH2Br), 1.93 (dd, CHH of TEMPO, J = 12.6 Hz, J = 4.1 Hz), 2.30 (t,

3 3 3 COCH2, J = 7.3 Hz), 3.28 (t, CH2Br, J = 6.7 Hz), 5.08 (tt, CH of TEMPO, J = 11.4 Hz,

3J = 4.3 Hz).

Scheme 2.15 Synthesis of

4-(6-cyanohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl

A solution of NaCN (85.2 mg, 1.74 mmol) in DMSO (20 mL) was added dropwise over 15 min to a solution of

4-(6-bromohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl (557 mg, 1.59 mmol) in

DMSO (10 mL) and stirred at 60 °C for 24 h. After reaction, the solution was diluted with

H2O (40 mL) and extracted 4 times with Et2O (25 mL each). The organic layers were combined, washed 2 times with H2O (25 mL each) and dried over MgSO4. After the solvent was removed from the filtrate by rotary evaporation, the residue was recrystallized from 15 mL Hexanes/EtOAc (7:1 v/v) to yield 0.3013 g (64.0%) of

4-(6-cyanohexanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl as an orange oil. 1H NMR:

4 1.23 (d, CH3 of TEMPO, J = 6.1 Hz), 1.4-1.7 (m, CHH of TEMPO and

2 3 COCH2(CH2)CH2Br), 1.93 (dd, CHH of TEMPO, J = 12.6 Hz, J = 4.3 Hz), 2.30 (t,

3 3 3 COCH2, J = 7.2 Hz), 2.34 (t, CH2Br, J = 6.72 Hz), 5.07 (tt, CH of TEMPO, J = 11.4 Hz,

3J = 4.3 Hz).

2.3.3 Nitroxide radical coupling of TEMPO derivatives with model compound

Scheme 2.16 Synthesis of HTEMPO quenched model compound

A solution of model compound (0.314 g, 1.18 mmol) and HTEMPO (0.174 g, 1.00 mmol) in EtOAc (15 mL) was degassed by 2 cycles of F-P-T. A solution of PMDETA

(0.271 g, 1.56 mmol) and CuBr (0.213 g, 1.48 mmol) in EtOAc (5 mL) was degassed by

3 cycles of F-P-T and stirred at RT for 10 min. After the prepared solution was added to flask under N2, it was further degassed by 3 cycles of F-P-T. A blue precipitate formed in the solution. The reaction was stirred at 50 °C for 18 h. The blue precipitate turned green after reaction. After filtration through basic alumina, the solvent was removed from the filtrate by rotary evaporation, and the yellow oil residue was purified by column chromatography (Rf = 0.4) using silica gel as the stationary phase and Hexanes/EtOAc

(5:3 v/v) as the eluant to yield 0.225 g (62.2%) of n-butyl 3-acetoxy-2-HTEPMO-

1 3 propionate as an orange oil. H NMR: 0.93 (t, CH2CH3, J = 7.3 Hz), 1.09-1.25 (m, CH3

3 of TEMPO), 1.3~1.5 (m, CHH of TEMPO and CH2CH3), 1.64 (quin, CH2CH2CH3, J =

6.9 Hz), 1.79 (m, CHH of TEMPO), 2.04 (s, CH3CO), 3.94 (m, CH of TEMPO), 4.14 (t,

3 2 3 OCH2CH2, J = 6.4 Hz), 4.25 (dd, CHCHHO, J = 12.6 Hz, J = 7.5 Hz), 4.50 (m, CHON and CHCHHO).

Scheme 2.17 Synthesis of 4-acryloxy-TEMPO quenched model compound

A solution of model compound (94 mg, 0.35 mmol) and HTEMPO (80 mg, 0.35 mmol) in EtOAc (5 mL) was degassed by 2 cycles of F-P-T. A solution of PMDETA (92 mg, 0.53 mmol) and CuBr (84 mg, 0.58 mmol) in EtOAc (5 mL) was degassed by 3 cycles of F-P-T and stirred at RT for 10 min. After the prepared solution was added to flask under N2, it was further degassed by 2 cycles of F-P-T. A blue precipitate formed in the solution. The reaction was stirred at 50 °C for 16 h. The blue precipitate turned green after reaction. After filtration through basic alumina, the solvent was removed from the filtrate by rotary evaporation, and the yellow oil residue was purified by column chromatography (Rf = 0.45) using silica gel as the stationary phase and Hexanes/EtOAc

(5:1 v/v) as the eluant to yield 0.101 g (69.1%) of n-butyl

3-acetoxy-2-(4-acryloxy-TEMPO)-propionate as an orange oil. 1H NMR: 1.02 (t,

3 CH2CH3, J = 7.0 Hz), 1.19 & 1.33 (s, CH3 of TEMPO), 1.48 (m, CH2CH3), 1.71 (m,

CHH of TEMPO and CH2CH2CH3), 1.94 (br, s, CHH of TEMPO), 2.13 (s, CH3CO), 4.22

3 2 3 (t, OCH2CH2, J = 6.1 Hz), 4.34 (dd, CHCHHO, J = 12.0 Hz, J = 8.0 Hz), 4.59 (m,

3 CHON and CHCHHO), 5.16 (m, CH of TEMPO), 5.89 (d, CHHb= trans to CO, J= 10.0

3 3 3 Hz), 6.10 (dd, =CHCO, J = 17.3 Hz, J = 10.0 Hz), 6.46 (d, CHaH= cis to CO, J = 17.3

Hz).

2.3.4 Nitroxide radical coupling of TEMPO derivatives with hyperbranched polyacrylate.

Scheme 2.18 General procedure of ATNRC

For all the NRC reaction, the ratio of Br in polymer/TEMPO derivatives/CuBr/PMDETA was kept as constant as 1/1/1/1. The polymer and TEMPO derivatives were first dissolved in 4 mL EtOAc. In a typical example, a solution of hyperbranched polyacrylate

(89 mg, 0.32 mmol Br) and TEMPO-OH (55 mg, 0.32 mmol) in EtOAc (4 mL) was degassed by 3 cycles of F-P-T. A solution of PMDETA (65 μL, 0.31 mmol) and CuBr (44 mg, 0.31 mmol) in EtOAc (1 mL) was degassed by 3 cycles of F-P-T and stirred at RT for 10 min. After the prepared solution was added to flask under N2. It was further degassed by 3 cycles of F-P-T. The reaction was stirred at RT for 44 h. The reaction was stopped by diluting with EtOAc (10 mL) and then passed the solution through basic alumina plug. After the solvent was removed by rotary evaporation, the residue was precipitated into THF/Hexanes (1/30 v/v) (30 mL) and dried under vacuum to yield 60.0 mg (51.3%) TEMPO-OH functionalized hyperbranched polyacrylate as a white gummy

37 solid. Mn: 35.3k, PDI: 2.77.

Table 2.1. Yields of Nitroxide Radical Coupling of Hyperbranched polyacrylates with

TEMPO derivatives

TEMPO TEMPO TEMPO TEMPO TEMPO TEMPO

derivatives -OH -mesyl -CN -N3 -acrylate

Yield* 51.3% 3 1.4 % 31.4% 24.2% 14.5%

(*:Yield is based on 100% coupling efficiency)

CHAPTER III

RESULTS AND DISCUSSIONS

3.1 1H and 13C NMR Spectra

Figure 3.1. 1H NMR spectrum of 2-bromo-3-hydroxypropionic acid

As shown in Figure 3.1, the methine proton of 2-bromo-3-hydroxypropionic acid is at a chiral center. Due to the different chemical environments of the two methylene protons, the methine resonance is a doublet of doublet at 4.42 ppm. The methylene protons also resonate as doublet of doublets due to coupling with the methine and the other methylene proton at 4.03 and 4.05 ppm. 39

Figure 3.2. 1H NMR spectrum of n-butyl 2-bromo-3-hydroxypropionate

According to Scheme 2.2, the carboxylic group was esterified with n-butanol.

Comparing Figures 3.1 and 3.2, the broad hydroxy resonance shifts upfield and become a triplet, while the methylene and methyl protons resonate at 4.22, 1.67 (quintet), 1,42

(sextet) and 0.94 (triplet) ppm with reasonable integration. The remaining resonances that are due to protons that are also in the starting material have shifted slightly.

Figure 3.3. 1H NMR spectrum of n-butyl 3-acetoxy-2-bromopropionate

n-Butyl 2-bromo-3-hydroxypropionate was reacted with acetyl chloride to produce n-butyl 3-acetoxy-2-bromopropionate (Scheme 2.3). The major changes in the spectra from Figure 3.2 to Figure 3.3 are the disappearance of the hydroxy resonance at 2.48 ppm and the appearance of the methyl resonance at 2.05 ppm (singlet), which demonstrates that the reaction was successful. The integrals are also consistent with the structure. The butyl resonances barely changed; however, one of the methylene resonances next to the chiral center shifted downfield and overlaps with the methine resonance.

Figure 3.4. 1H NMR spectrum of acrylic anhydride

Figure 3.4 presents the 1H NMR spectrum of acrylic anhydride, which was synthesized according to Scheme 2.4. Protons a, b, c have different chemical environments, and thus have different chemical shifts, with each coupling to the other two. The two doublet of doublets at 6.53-6.59 ppm and 6.06-6.09 ppm are the methylene resonances. The doublet of doublets at 6.14-6.23 ppm is the methine resonance. The integration is also consistent with the structure.

Figure 3.5. 1H NMR spectrum of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate

As outlined in Scheme 2.5, we used acrylic anhydride to react with n-butyl

2-bromo-3-hydroxypropionate to produce the (2-bromo-2-n-butoxycarbonyl)ethyl acrylate inimer. The 1H and 13C NMR spectra are presented in Figure 3.5 and Figure 3.6, respectively. Comparing the structure of the inimer (Figure 3.5) and model compound

(Figure 3.3), the main difference is the change from methyl group to vinyl group. From the 1H NMR spectra in Figure 3.3 and Figure 3.5, the disappearance of the methyl resonance at 2.05 ppm and the appearance of three doublet of doublets at 5.87-6.47 ppm

(typical vinyl resonances) confirms the successful synthesis of

(2-bromo-2-n-butoxycarbonyl)ethyl acrylate.

Figure 3.6. 13C NMR spectrum of (2-bromo-2-n-butoxycarbonyl)ethyl acrylate

The 13C NMR spectrum in Figure 3.6 shows distinct resonances of each unique carbon on the product (carbonyl at 165 and 168 ppm, vinyl carbon at 127 and 132 ppm, saturated carbons at 66, 64, 41, 30, 19 and 14 ppm), with no other resonances. This demonstrates that (2-bromo-2-n-butoxycarbonyl)ethyl acrylate was successfully synthesized.

Figure 3.7. 1H NMR spectrum of poly(2-bromo-2-n-butoxycarbonyl)ethyl acrylate

According to Scheme 2.6, the hyperbranched polyacrylate was synthesized by homopolymerization of the inimer. The broadened resonances in Figure 3.7 compared to the sharp resonances in Figure 3.5 at the same chemical shifts clearly confirm the formation of polymer. At the same time, the vinyl resonances at 5.87-6.47 ppm almost disappeared, and the resonances of the backbone protons resonates at 2.40 and 1.96 ppm.

The molecular weight characterization, which will be presented later, also confirms that polymer was generated.

Figure 3.8. 1H and 13C NMR spectra of 4-mesyl-TEMPO. The “*” peaks are due to phenyl hydrazine.

Phenyl hydrazine was used to quench the paramagnetic free radical of the nitroxides, and is therefore present in the 1H and 13C NMR spectra of all of the nitroxide radicals.

Since the TEMPO ring is not on the same plane, the chemical shift of two methyl groups on the same side are not the same. The two methylene protons on the same carbon are also not equivalent. These two types of methylene protons in TEMPO are coupled to each other and the methine proton. As a consequence, the methyl protons resonate as two singlets and the methylene protons resonate two doublet of doublets, one of which looks like a triplet due to similar coupling constants. This applies to all of the TEMPO derivatives.

Methanesulfonyl chloride was used to reacted with TEMPO-OH to produce

4-mesyl-TEMPO (Scheme 2.8). The 1H NMR spectrum in Figure 3.8 of 4-mesyl-TEMPO shows the TEMPO methyl resonance at 1.24 ppm, the methylene resonances at 1.8 and

2.1 ppm, and the methine resonance at 4.95 ppm. The mesyl methyl protons resonate at

3.01 ppm as singlet. The corresponding 13C NMR spectrum in Figure 3.8 shows the distinct resonances of TEMPO. The methyl resonances have two different chemical shifts

(one at 20.5 ppm, and the other at 31.9 ppm), which are consistent with the 1H NMR spectrum. The mesyl carbon resonates at 38.9 ppm.

Figure 3.9. 1H and 13C NMR spectra of 4-acryloxy-TEMPO synthesized from acryloyl chloride. The “*” peaks are due to phenyl hydrazine.

Acryloyl chloride was used to reacted with TEMPO-OH to produce

4-acryloxy-TEMPO (Scheme 2.10). The 1H NMR spectrum in Figure 3.9 shows all of the

TEMPO resonances (methyl at 1.13 ppm (two singlets), methylene at 1.55 ppm (doublet of doublets) and 1.87 ppm (doublet of doublets), methine at 5.04 ppm (triplet of triplets).

At the same time, it shows the typical vinyl resonances at 5.7-6.3 ppm, which is due to the acryloyl group. The 13C NMR spectrum in Figure 3.9 shows distinct resonances of

TEMPO including two methyl resonances. The carbonyl resonance at 165.7 ppm and vinyl resonates at 130.5 and 128.7 ppm are due to the acrylate substitution.

Figure 3.10. 1H and 13C NMR spectra of 4-(4-nitrophenylacetyloxy)-TEMPO. The “*” peaks are due to pentafluorophenyl hydrazine.

4-Nitrophenylacetic acid was reacted with TEMPO-OH to produce

4-(4-nitrophenylacetyloxy)-TEMPO (Scheme 2.12). The 1H NMR spectrum in Figure

3.10 shows all of the TEMPO resonances (methyl at 1.21 ppm (two singlets), methylene at 1.61 ppm (doublet of doublets) and 1.90 ppm (doublet of doublets), methine at 5.08 ppm (triplet of triplets). At the same time it shows two doublet of doublets at 7.47 and

8.20 ppm as typical aromatic resonances from the nitrobenzol group. The 13C NMR spectrum in Figure 3.10 shows distinct resonances of TEMPO including two methyl resonances. The carbonyl resonance at 169.70 ppm, aromatic carbons at 147.3, 141.3,

130.2 and 123.7 ppm, and methylene resonance at 41.2 ppm are due to the

4-nitrophenylacetyloxy substitution.

Figure 3.11. 1H and 13C NMR spectra of 4-(6-bromohexanoyloxy)-TEMPO. The “*” peaks are due to phenyl hydrazine.

6-Bromohexanoic acid was used to reacted with TEMPO-OH to produce

4-(6-bromohexanoyloxy)-TEMPO (Scheme 2.13). The 1H NMR spectrum in Figure 3.11 shows methyl and methine resonances of TEMPO at 1.24 ppm (two singlets) and 5.08 ppm (triplet of triplets). However, the six methylene protons (e, f, g) and the four methylene protons of TEMPO overlap at 1.3-2.0 ppm, and are hard to differentiate. The triplet at 2.30 ppm is from the methylene ortho to the carbonyl group and the triplet at

3.41 ppm are from the methylene ortho to bromine. These two resonances as well as their integrals demonstrate the successful synthesis of 4-(6-bromohexanoyloxy)-TEMPO. The

13C NMR spectrum in Figure 3.11 shows distinct resonances of TEMPO including two methyl resonances. The carbonyl resonance at 173.0 ppm, and the methylene resonances at 34.3, 33.6, 32.4, 27.6 and 24.1 ppm are due to the 6-bromohexanoyloxy group.

Figure 3.12. 1H and 13C NMR spectra of 4-(6-azidohexanoyloxy)-TEMPO. The “*” peaks are due to phenyl hydrazine.

The bromide on 4-(6-bromohexanoyloxy)-TEMPO was substituted by azide via reaction with sodium azide to produce 4-(6-azidohexanoyloxy)-TEMPO (Scheme 2.14).

The 1H NMR spectrum in Figure 3.12 shows methyl, methine and one of the methylene resonances of TEMPO at 1.24 ppm (two singlets), 5.08 ppm (triplet of triplets), and 1.94 ppm (doublet of doublets). However, the e, f, g methylene resonances and the methylene resonances of TEMPO overlap at 1.3-1.7 ppm, and are hard to differentiate. Compared to the 1H NMR spectrum of 4-(6-bromohexanoyloxy)-TEMPO in Figure 3.11, the 1H NMR spectrum in Figure 3.12 shows that the resonance of methylene ortho to carbonyl group at

2.30 ppm stays the same, while the other triplet at 3.41 ppm shifts upfield to 3.28 ppm, which demonstrates the successful substitution of bromide into azide. The 13C NMR spectrum in Figure 3.12 shows distinct resonances of TEMPO including two methyl resonances. The carbonyl resonance at 173.0 ppm, and the methylene resonances at 51.2,

34.3, 28.5, 26,2 and 24.4 ppm are due to the 6-azidohexanoyloxy group.

Figure 3.13. 1H and 13C NMR spectra of 4-(6-cyanohexanoyloxy)-TEMPO. The “*” peaks are due to phenyl hydrazine.

The bromide on 4-(6-bromohexanoyloxy)-TEMPO was also substituted by cyanide via reaction with sodium cyanide to produce 4-(6-cyanohexanoyloxy)-TEMPO (Scheme

2.15). The 1H NMR spectrum in Figure 3.13 shows methyl, methine and one of the methylene resonances of TEMPO at 1.23 ppm (two singlets), 5.07 ppm (triplet of triplets), and 1.92 ppm (doublet of doublets). However, the e, f, g methylene resonances and the methylene resonances of TEMPO overlap at 1.3-1.7 ppm, and are hard to differentiate.

Compared to the 1H NMR spectrum of 4-(6-bromohexanoyloxy)-TEMPO in Figure 3.11, the 1H NMR spectrum in Figure 3.13 shows that the resonance of methylene ortho to carbonyl group at 2.30 ppm stays the same while the other triplet at 3.41 ppm shifts upfield to 2.34 ppm and overlaps with the other triplet, which demonstrates the successful substitution of bromide into cyanide. The 13C NMR spectrum in Figure 3.13 shows distinct resonances of TEMPO including two methyl resonances. The carbonyl resonance at 172.9 ppm, and the methylene resonances at 34.1, 28.1, 25.1, 24.1, and 17.0 ppm are due to the 6-cyanohexanoyloxy group.

Figure 3.14. 1H NMR spectra of n-butyl 3-acetoxy-2-HTEPMO-propionate and

TEMP-OH. The “*” peaks are due to phenyl hydrazine.

In order to establish conditions for quenching radicals from the hyperbranched poly(n-butyl acrylate) with the nitroxide derivatives, we first tested their ability to quench radicals from the model compound. Scheme 2.16 shows the ATNRC of model compound with TEMPO-OH in ethyl acetate at 50 °C.

The success of this reaction can be seen by comparing the 1H NMR spectra in

Figures 3.3 and 3.14. The 1H NMR spectrum of n-butyl

3-acetoxy-2-HTEPMO-propionate in Figure 3.14 shows the methyl resonance on the butyl group at 0.93 ppm (triplet), the methyl resonance from the acryloyl group at 2.04 ppm (singlet), and the methylene (g) at 4.14 ppm (triplet) (see the 1H NMR spectrum of model compound in Figure 3.3). It also shows the methyl resonance of TEMPO-OH at

1.09-1.25 ppm, one of the methylene resonance at 1.80 ppm, and the methine resonance at 3.94 ppm (see the 1H NMR spectrum of TEMPO-OH in Figure 3.14). Specifically, the e ,f methine and methylene protons shift from 4.44 and 4.39 ppm, to 4.50 and 4.26 ppm.

These shifts and the increased resolution of e and f confirm the successful coupling of

TEMPO-OH with the model compound.

Figure 3.15. 1H NMR spectrum of n-butyl 3-acetoxy-2-(4-acryloxy-TEMPO)-propionate.

As shown in Scheme 2.17, the model compound was also coupled with

4-acryloxy-TEMPO. The 1H NMR spectrum in Figure 3.15 shows the methyl resonance on the butyl group at 1.02 ppm (triplet), the methyl resonance on the acryloyl group at

2.13 ppm (singlet), and the methylene (g) at 4.22 ppm (triplet) (see the 1H NMR spectrum of model compound in Figure 3.3). It also shows the methyl resonance of

4-acryloxy-TEMPO at 1.09-1.33 ppm, one of the methylene resonance at 1.94 ppm, the methine resonance at 5.16 ppm, and the vinyl resonances at 5.87-6.48 ppm (see the 1H

NMR spectrum of 4-acryloxy-TEMPO in Figure 3.9). Specifically, the e, f methine and methylene protons shift from 4.44 and 4.39 ppm, to 4.59 and 4.33 ppm. These shifts and the increased resolution of e and f confirm the successful coupling of 4-acryloxy-TEMPO with model compound.

Since the model radical quenching reactions were successful, we extended the quenching reactions to hyperbranched poly(n-butyl acrylate). However, as outlined in

Scheme 2.18, the temperature was decreased from 50 °C to room temperature because lower temperature increase the stability carbon-nitroxide bond, thus the concentration of free carbon radicals was decreased to minimize inter-polymer combination termination.

Figure 3.16. 1H NMR spectrum of TEMPO-OH functionalized hyperbranched poly(n-butyl)acrylate.

The 1H NMR spectrum of TEMPO-OH functionalized hyperbranched poly(n-butyl)acrylate in Figure 3.16 shows the methyl resonance at 1.00 ppm, the methylene resonance (f) at 4.24 ppm, and the methylene and methine resonances (d, e) at

4.54 ppm from the hyperbranched polyacrylate (compare to Figure 3.7). It also shows the methyl resonance at 1.22 ppm, and the methine resonance at 3.89 ppm from the

TEMPO-OH group. The other resonances are overlapped. Figure 3.16 confirms the successful coupling of TEMPO-OH with hyperbranched poly(n-butyl)acrylate in 83% coupling efficiency. (The coupling efficiency was calculated from integration of methine resonance at 3.89 ppm of TEMPO-OH and methyl resonance at 1.00 ppm of hyperbranched acrylate.)

Figure 3.17. 1H NMR spectrum of 4-mesyl-TEMPO functionalized hyperbranched poly(n-butyl)acrylate. The “*” peaks are due to THF.

The 1H NMR spectrum of 4-mesyl-TEMPO functionalized hyperbranched poly(n-butyl)acrylate in Figure 3.17 shows the methyl resonance at 0.96 ppm, the methylene resonance (f) at 4.16 ppm, and the methylene and methine resonances (d, e) at

4.47 ppm from the hyperbranched polyacrylate (compare to Figure 3.7). It also shows the methyl resonance at 1.22 ppm, methyl resonance at 3.01 ppm, and the methine resonance at 4.89 ppm from 4-mesyl-TEMPO (compare to Figure 3.8). The other resonances are overlapped. The 1H NMR spectrum confirms the successful coupling of 4-mesyl-TEMPO with hyperbranched poly(n-butyl)acrylate in 89% coupling efficiency. (The coupling efficiency was calculated from integration of methyl resonance at 3.01 ppm of

4-mesyl-TEMPO and methyl resonance at 0.96 ppm of hyperbranched acrylate.)

Figure 3.18. 1H NMR spectrum of 4-acryloxy-TEMPO functionalized hyperbranched poly(n-butyl)acrylate. The “*” peaks are due to THF and BHT.

The 1H NMR spectrum of 4-acryloxy-TEMPO functionalized hyperbranched poly(n-butyl)acrylate in Figure 3.18 shows the methyl resonance at 0.95 ppm, the methylene resonance (f) at 4.13 ppm, and the methylene and methine resonances (d, e) at

4.48 ppm from hyperbranched polyacrylate (compare to Figure 3.7). It also shows the methyl resonance at 1.22 ppm, methine resonance at 5.08 ppm, and the vinyl resonances at 5.77-6.39 ppm from 4-acryloxy-TEMPO (compare to Figure 3.9). The other resonances are overlapped. The 1H NMR spectrum confirms the successful coupling of

4-acryloxy-TEMPO with hyperbranched poly(n-butyl)acrylate in 84% coupling efficiency. (The coupling efficiency was calculated from integration of vinyl resonances at 5.77-6.39 ppm of 4-acryloxy-TEMPO and methyl resonance at 0.95 ppm of hyperbranched acrylate.)

Figure 3.19. 1H NMR spectrum of 4-(6-azidohexanoyloxy)-TEMPO functionalized hyperbranched poly(n-butyl)acrylate. The “*” peaks are due to THF.

The 1H NMR spectrum of 4-(6-azidohexanoyloxy)-TEMPO functionalized hyperbranched poly(n-butyl)acrylate in Figure 3.20 shows the methyl resonance at 0.96 ppm, the methylene resonance (f) at 4.13 ppm, and the methylene and methine resonances (d, e) at 4.49 ppm from hyperbranched polyacrylate (compare to Figure 3.7).

It also shows the methyl resonance at 1.21 ppm, methylene resonance (j, n) at 2.28 and

3.28 ppm, and the methine resonance at 5.00 ppm from 4-(6-azidohexanoyloxy)-TEMPO

(compare to Figure 3.12). The other resonances are overlapped. The 1H NMR spectrum confirms the successful coupling of 4-(6-azidohexanoyloxy)-TEMPO with hyperbranched poly(n-butyl)acrylate in 80% coupling efficiency. (The coupling efficiency was calculated from integration of methylene resonance at 3.28 ppm of

4-(6-azidohexanoyloxy)-TEMPO and methyl resonance at 0.96 ppm of hyperbranched acrylate.)

Figure 3.20. 1H NMR spectrum of 4-(6-cyanohexanoyloxy)-TEMPO functionalized hyperbranched poly(n-butyl)acrylate.

The 1H NMR spectrum of 4-(6-cyanohexanoyloxy)-TEMPO functionalized hyperbranched poly(n-butyl)acrylate in Figure 3.20 shows the methyl resonance at 0.96 ppm, the methylene resonance (f) at 4.16 ppm, and the methylene and methine resonances (d, e) at 4.48 ppm from hyperbranched polyacrylate (compare to Figure 3.7).

It also shows the methyl resonance at 1.22 ppm, methylene resonance (j, n) at 2.36 and

2.29 ppm, and the methine resonance at 4.99 ppm from 4-(6-cyanohexanoyloxy)-TEMPO

(compare to Figure 3.13). The other resonances are overlapped. The 1H NMR spectrum confirms the successful coupling of 4-(6-cyanohexanoyloxy)-TEMPO with hyperbranched poly(n-butyl)acrylate with 82% coupling efficiency. (The coupling efficiency was calculated from integration of methyl resonance at 4.99 ppm of

4-(6-cyanohexanoyloxy)-TEMPO and methyl resonance at 0.96 ppm of hyperbranched acrylate.)

3.2 Nitroxide Radical Coupling Results

Table 3.1. GPC Results of Polymer before and after Coupling ( RI detector, THF as

solvent)

TEMPO TEMPO TEMPO TEMPO TEMPO TEMPO derivatives -OH -mesyl -CN -N3 -acrylate

Coupling 83% 89% 82% 80% 84%

Efficiency*

Polymer Mn 15.2k 15.6k 14.4k 14.4k 14.4k before PDI 5.42 6.41 3.56 3.56 3.56 coupling

Polymer Mn 35.3k 6.6k 20.3k 20.2k 19.9k after PDI 2.77 2.04 3.03 3.49 2.82 coupling

Theoretical Mn 23.0k 28.0k 26.9k 27.3k 24.2k after coupling

*:assuming no combination termination during polymerization

Figure 3.21. GPC Traces of hyperbranched polyacrylate before and after coupling

reaction with 4-acryloxy-TEMPO

The gel permeation chromatography (GPC) results in Table 3.1 of the hyperbranched polyacrylates before and after functionaliztion with 4-acryloxy-TEMPO demonstrates that the molecular weight increases after coupling reaction (Figure 3.21). The GPC results of other compounds are summarized in Table 3.1 and their chromatograms presented in the Appendix. The molecular weight was based on linear polystyrene standard using an RI detector. The branched polymers have smaller hydrodynamic volumes than the corresponding linear polymer of similar molecular weight, and the hydrodynamic volumes are greatly affected by their solubility in the eluting solvent.35 As

68 a result, the calculated molecular weight are presumably lower than the real molecular weight, especially at higher molecular weight. This presumably explains why the experimental Mn is lower than the theoretical value. The PDIs also decreased after coupling. One possible explanation is that the highly functionalized polymers have larger absorption on basic alumna (used to remove copper) especially the ones with larger branching density. As a consequence, some highly branched polymer may have been trapped in the basic alumina column, resulting in lower yield and PDI. On the other hand,

PDI tends to decrease after precipitation. Differences in the coupling efficiency of different nitroxides may have small influence on the molecular weights and PDI after coupling reaction. Less than 100% coupling efficiency means more possibility for combination termination between different polymers, which cause larger increase in the molecular weight. And since smaller molecules are more easier to combine than larger ones, the whole PDI tends to get smaller due to decrease of smaller molecules. On the other hand, intramolecular coupling would also decreases PDI and hydrodynamic volume.

For all the five nitroxide, only TEMPO-mesyl coupling resulted in decreased molecular weight, suggesting TEMPO-mesyl degrades the hyperbranched polyacrylates.

CHAPTER IV

CONCLUSION

4-Hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO-OH) was successfully reacted with methanesulfonyl chloride, 4-nitrophenylacetic acid, acryloyl chloride, and

6-bromohexanoic acid to produce TEMPO derivatives with four different functional groups, which can be further modified. For example, the

4-(6-bromohexanoyloxy)-TEMPO was converted to 4-(6-cyanohexanoyloxy)-TEMPO and 4-(6-azidohexanoyloxy)-TEMPO.

The coupling efficiency of Nitroxide Radical Coupling between the hyperbranched polyacrylates and three nitroxides was found to be greater than 80%. There were no detectable side products. In addition, despite the bad result of coupling with

TEMPO-OSO2CH3, the molecular weight of the hyperbranched polyacrylate had largely increased after coupling. This confirmed that Nitroxide Radical Coupling can be an efficient functionalization method for hyperbranched polyacrylates with halogen chain ends.

However, problems such as lower PDI after coupling and low yield still have to be solved in the future.

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APPENDIX

GPC traces of polymers (RI detector)

Hyperbranched poly(n-butyl)acrylate

HTEMPO functionalized hyperbranched poly(n-butyl)acrylate

4-methanesulfonate-TEMPO functionalized hyperbranched poly(n-butyl)acrylate

4-(6-cyanohexanoyloxy)-TEMPO functionalized hyperbranched poly(n-butyl)acrylate

4-(6-azidohexanoyloxy)-TEMPO functionalized hyperbranched poly(n-butyl)acrylate

4-acryloxy-TEMPO functionalized hyperbranched poly(n-butyl)acrylate