Evaluating the effect of termination by chain-chain coupling in living free-radical polymerizations

Article abstract of DOI:10.1071/CH03041

A novel approach based on the reaction of multifunctional star polymers with chromophore-labelled linear polymers is presented for evaluating the extent of termination by chain-chain coupling during living free-radical polymerizations. A mixed initiating

Full text of DOI:10.1071/CH03041

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CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2003, 56, 775–782
Evaluating the Effect of Termination by Chain–Chain Coupling in
Living Free-Radical Polymerizations
Jeffrey Pyun,A,B Ian Rees,A Jean M. J. FréchetB and Craig J. HawkerB,C
A Center for Polymeric Interfaces and Macromolecular Assemblies, IBM Almaden Research Center,
650 Harry Road, San Jose, CA 95120-6099, USA.
B Department of Chemistry, University of California, Berkeley, CA 94720-1460, USA.
C Author to whom correspondence should be addressed (e-mail: hawker@almaden.ibm.com).
A novel approach based on the reaction of multifunctional star polymers with chromophore-labelled linear polymers
is presented for evaluating the extent of termination by chain–chain coupling during living free-radical poly-
merizations. A mixed initiating system consisting of an unlabelled, multifunctional initiator and an excess of a
monofunctional alkoxyamine initiator containing a chromophore, such as pyrene, is used to initiate the living poly-
merization of vinyl monomers leading to a mixture of star and linear polymers. The occurrence of chain–chain
coupling is readily identified and quantified by isolating the star polymer that is obtained and elucidating the
level of incorporation of pyrene units by UV/vis spectroscopy. This allows the level of chain–chain coupling to be
determined since the inclusion of pyrene into the star structure is a direct result of termination by radical coupling.
Manuscript received: 3 February 2003.
Final version: 1 April 2003.
The renaissance of research activity in the area of free-radical
polymerizations has led to the development of various forms
of living free-radical procedures (LFRP), with the three main
techniques at the present being stable free-radical (nitroxide)
polymerizations (SFRP),[1] atom-transfer radical polymeri-
zation (ATRP),[2] and radical addition, fragmentation, and
transfer procedures (RAFT).[3] The advantages of living free-
radical polymerizations, namely its versatility, synthetic ease,
and compatibility with a wide variety of functional groups
and macromolecular architectures, are key features driving
this rapidly developing field. Interestingly, this renaissance
has also coincided with the growing importance of well-
defined macromolecules in the blossoming field of nanoscale
science, for which many of the materials available from living
free-radical procedures are perfectly suited.[4]
to evaluate the extent of these termination reactions. This is
especially true for chain–chain coupling reactions since the
effect of minor amounts of coupling is magnified due to the
multifunctional nature of the initiators that are employed for
thesynthesisofthesebranchedarchitectures.Thismanuscript
describesthedevelopmentofageneralprocedurefortheiden-
tification and evaluation of chain–chain coupling reactions
during living free-radical polymerizations.
To assess the level of chain–chain coupling reactions in
LFRP, a novel approach has been developed based on the
crossover reaction[10] between an unfunctionalized, multi-
functional alkoxyamine initiator (1) and a functionalized,
monoalkoxyamine initiator (2). As depicted schematically
in Scheme 1, in the absence of radical–radical coupling
reactions, polymerization of a vinyl monomer using both
the dodeca-functionalized initiator (1) and the chromophore-
labelled initiator (2) gives a mixture of a 16-arm star polymer
(3) and a linear polymer (4). If crossover did not occur, only
the linear polymer (4) would contain a single chromophore
(F) at the chain end. However, if radical–radical coupling
reactions do occur during the polymerization, a mixture of
coupled products would be obtained, one of which would be
the crossover derivative (5) in which the growing arms of
the star polymer undergo coupling with functionalized linear
chains.
From the initial report[5] of using a multifunctional
alkoxyamine initiator to prepare star polymers, the applica-
tion of LFRP to the preparation of complex macromolecular
architectures has blossomed and a myriad of different struc-
tures, ranging from stars,[6] hyperbranched,[7] comb,[8] to
hybrid dendritic–linear macromolecules,[9] have been pre-
pared. However, one feature that is typically neglected in the
analysis and discussion of such structures is the occurrence
of side reactions or termination processes that are typically
associated with traditional free-radical chemistry. In LFRP
theseprocessesstilloccur, albeitatareducedlevel.Therefore,
to better understand the potential use of LFRP procedures
for the preparation of complex macromolecular architectures
and the associated level of possible impurities, it is important
As a result, a partially terminated product (5) is obtained
in which at least one of the 16 arms of the star polymer has
been terminated with a chromophore-labelled linear chain.
Due to the molecular weight differences between the linear
© CSIRO 2003
10.1071/CH03041
0004-9425/03/080775

776
J. Pyun et al.
I
I
I
I
N
I
I
O
HO
HO
I
ϩ
I
I
(2)
OH
I
I
I
(7)
I
Cl
I
I
R
I
I
(6)
(1)
K2CO3
[18]crown-6
N
O
O
O
CBr4/PPh3
(Alk)2-[G-1]-Br
(9)
OH
(4)
O
star–chain
coupling
N
(3)
(8)
Scheme 2. Convergent synthesis of alkoxyamine-terminated
Fréchet-type dendrimers.
HO
O
ϩ
O
OMe
HO
(5)
(10)
1. HCl 2. LiAlH4
Scheme 1. Graphical representation of the strategy for detecting
radical–radical coupling during living free-radical polymerization.
O
O
O
O
O
O
O
CBr4/PPh3
chains (4) and the star polymers (3) and (5), separation can
be achieved by a number of different techniques and the level
of incorporation of the chromophore in the star polymer can
be determined by spectroscopy (Scheme 1).
Br
Hünig’s Base
OH
O
(11)
(12)
HO
The starting point for this strategy is, therefore, to use
a multifunctional initiator such as (1), and it was initially
envisaged that the appropriately functionalized Fréchet-type
dendrimers would be employed due to the large body of litera-
ture concerning their synthesis and properties.[11] Employing
a convergent approach[12] to the synthesis of multifunc-
tional alkoxyamine initiators, the chloromethyl-substituted
alkoxyamine (6) was treated with 3,5-dihydroxybenzyl
alcohol (7) underWilliamson etherification conditions to give
the first generation dendritic fragment (8), which contains
two alkoxyamine initiating centres. Bromination of (8) with
carbon tetrabromide/triphenylphosphine gives the benzyl
bromide (Alk)2-[G-1]-Br (9) (Scheme 2). However, the yields
obtained for the synthesis of (8) and (9) were poor (50–60%)
and significantly below those normally obtained for Fréchet-
type dendrimers. This trend of decreased yields accelerated
for the second-generation derivatives, which precluded the
use of a convergent approach for the synthesis of multifunc-
tional dendritic alkoxyamines. One possible rationale for the
lowered efficiency of dendrimer construction is the presence
of the alkoxyamine groups at the chain ends, which leads to
K2CO3/[18]crown-6
OH
HO
O
O
O
O
O
O
O
O
O
O
O
O
CBr4/PPh3
Hünig’s Base
OH
Br
O
O
O
O
O
O
(13)
O
(14)
O
Scheme 3. Divergent synthesis of THP-terminated Fréchet-type
dendritic fragments (13) and (14).
unwanted side reactions. As a result, a divergent approach[13]
tothesynthesisofalkoxyamine-substitutedFréchet-typeden-
drimers was developed, since this permits the alkoxyamine
groups to be introduced in the final step of the synthesis.
For a divergent synthesis of Fréchet-type dendrimers to
be successful, a critical feature is the choice of protecting

Evaluating the Effect of Termination in Living Free-Radical Polymerizations
777
OH
HO
O
O
HO
OH
HO
O
O
O
O
O
O
O
O
OH
OH
ϩ
Br
HO
HO
O
N
O
O
HO
O
(15)
ϩ
O
O
O
(14)
K2CO3/[18]crown-6
Cl
(6)
O
O
O
OH
O
O
O
O
O
O
O
O
O
O
O
O
OH
K2CO3/[18]crown-6
O
HO
O
O
HO
OH
O
(17)
O
O
O
O
N
O
N
O
O
O
O
N
O
O
O
O N
O
O
N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
(16)
O
N
O
O
O
O
pTSA
OH
O
HO
O
HO
OH
N
O
O
O
O
O
O
OH
O
O
HO
HO
O
N
O
O
O
O
O
O
O
O N
O
N
O
O
OH
O
(18)
O
N
N
O
OH
HO
Scheme 5. Synthesis of alkoxyamine-functionalized polyether den-
drimer (18).
HO
OH
(17)
benzyl bromide (12) was obtained in greater than 90%
yield. Alkylation of 3,5-dihydroxybenzyl alcohol with (12)
proved to be a facile process giving the second-generation
alcohol (13), and bromination in the presence of Hünig’s base
afforded the bromide (14) with four THP-protected phenolic
groups at the chain ends (Scheme 3).
Coupling of (14) with the triphenolic core (15) then
gave the dendrimer (16), which could be deprotected by
treatment with p-toluenesulfonic acid (pTSA) in a mixture
of tetrahydrofuran and methanol, to give the dodecaphe-
nol (17) (Scheme 4). Alkylation of dodecaphenol (17) with
the chloromethyl-substituted alkoxyamine (6) proved to be
a facile process which resulted in high yields of the initiator
functionalized dendrimer (18). NMR and MALDI mass spec-
trometry confirmed that (18) had 12 alkoxyamine-initiating
groups attached to a central dendritic core (Scheme 5).
With the unfunctionalized dendritic initiator (18), the
precursor to the desired 12-arm star polymers, in hand,
Scheme 4. Divergent synthesis of phenolic-terminated Fréchet-type
dendrimer (17).
group for the phenolic functionalities since it must be stable
to the alkylation and bromination reactions used in construc-
tion of the dendrimer, and deprotection must occur cleanly
and without any degradation of the dendritic benzyl ether
bonds. Based on these criteria, the tetrahydropyranyl (THP)
functionality was selected as the protecting group and intro-
duced by acid-catalyzed addition of 3,4-dihydro-2H-pyran
to methyl 3,5-dihydroxybenzoate (10), followed by lithium
aluminum hydride reduction of the ester to give the benzyl
alcohol (11) in high yield (Scheme 3). Bromination of (11)
under standard (CBr4/PPh3) conditions gave poor yields of
the benzyl bromide due to acid-catalyzed deprotection of the
THP protecting groups. The addition of one equivalent of
diisopropylethylamine (Hünig’s base) to the reaction mix-
ture was found to eliminate this side reaction and the desired

778
J. Pyun et al.
N
N
O
O
N
O
O N
N
O
O
O
O
O
O
O
O
O
N
O
O
O
N
O
O
H
O
ϩ
O
N
O
O
O
O
O
O
O
N
O
O
O
(19)
O
O N
O
N
O
O
N
N
(18)
Styrene
ϩ
O
(3)
(4)
Scheme 6. Polymerization of styrene initiated by a mixture of the dodeca-initiator (18) and the pyrene-functionalized initiator (19).
a functionalized alkoxyamine was prepared. The pyrene-
functionalized alkoxyamine (19) was selected based on
our previous work[14] on the determination of the relative
incorporation of chain end functional groups.
star polymer structures. While this is expected for the lin-
ear polymer (4) due to the use of the functionalized initiator
(19), the observation of pyrene absorbances for the star poly-
mer is confirmation of an intermolecular coupling reaction
between the growing linear polymer chain (4) and the 12-arm
star polymer (3). As a result, the peak at 33.5 mL elution is
an overlay of the unfunctionalized 12-arm star (3) and the
pyrene-functionalized 12-arm star (5).
Separation of the mixture of (3) and (5) from the lin-
ear polymers was accomplished by preparative GPC due to
the dramatic differences in molecular weight. The absence
of pyrene-functionalized linear polymers (i.e. (4)) from the
purified mixture of 12-arm stars was confirmed by rigor-
ous multi-dimensional GPC analysis (combined RI and UV
detectors), and the relative percentage of pyrene function-
alized star (5) to unfunctionalized star (3) could then be
calculated from the total pyrene absorbance. In the case of
the above polymerization, which reached a conversion of
In order to minimize the occurrence of coupling reactions
between star polymers, an excess[15] of the functionalized
alkoxyamine (19) was employed in the polymerization reac-
tion of styrene (200 equivalents per alkoxyamine group),
which was allowed to proceed to 84% conversion (Scheme 6).
As can be seen in Figure 1, two symmetrical and narrow poly-
dispersity peaks were observed eluting at 33.5 and 38.0 min.
The former corresponds to the 12-arm star polymer (3) (Mn
195 000; PDI 1.08) and the latter to the pyrene-functionalized
linear polymer (4) (Mn 18 000; PDI 1.06). Significantly,
examination of the three-dimensional UV/vis–gel permea-
tion chromatography (GPC) plot revealed absorbances at
320–360 nm for both peaks, which demonstrates that the
pyrene functionality is incorporated into both the linear and

Evaluating the Effect of Termination in Living Free-Radical Polymerizations
779
20
15
10
5
0.60
0.50
0.40
0.30
0.20
0.10
0.00
225.00
300.00
nm
375.00
30.00
32.00
34.00
36.00
38.00
40.00
Elution volume
0
0
20
40
60
80
100
Fig. 1. Three-dimensional UV/vis–GPC plot (elution volume
versus wavelength versus absorbance) for the polymerization of 200
equivalents of styrene at 120◦C initiated by a mixture of (18) and (19).
Percent conversion
Fig. 3. Variation in the percent of pyrene incorporation with percent
conversion for the polymerization of 200 equivalents of n-butyl acrylate
at 120◦C initiated by a mixture of (18) and (19).
20
15
10
5
alkoxyamine) gives a transient or propagating radical and
a persistent radical (i.e. the nitroxide). While the persistent
radical only undergoes reaction with the transient radical to
regenerate the dormant species, the propagating radical can
undergo reaction with monomer, the persistent radical, or
itself. In the case of reaction with the persistent radical, or
monomer and persistent radical, this leads to regeneration of
the dormant species. However, reaction with another propa-
gating radical (i.e. radical–radical coupling) leads to coupling
and an overall reduction in the concentration of propagat-
ing radicals. As a result, the concentration of the persistent
radical slowly increases, which gives rise to the persistent rad-
ical effect and leads to control of the polymerization process.
Theoretical studies by Fischer et al.[18] have predicted this
increase in the concentration of persistent radicals and asso-
ciated decrease in concentration of transient radicals through
radical–radical coupling to occur in the very early stages of
the polymerization. This is also consistent with the expected
decrease in the rate of the intermolecular coupling reac-
tions as the degree of polymerization of the polymer chains
increase due to steric effects.
To more fully understand this process, the polymerization
of styrene in the presence of a mixture of (18) and (19) was
repeatedwith50and400equivalentsofstyrene. Inbothcases,
the level of pyrene incorporation was essentially the same
at all conversions as that observed for reactions with 200
equivalents of styrene. These three experiments were then
repeated with n-butyl acrylate as the monomer instead of
styrene, and for these examples, 5 mol-% of the free nitrox-
ide was added to control the polymerization and give a living
system. As can be seen in Figure 3, the overall profile of the
relationship between the level of pyrene incorporation and
percent conversion for n-butyl acrylate is similar to that for
styrene. The majority of coupling reactions occur at very low
conversions, and above 10% conversion the level of pyrene
incorporation increases at a much reduced rate. However, the
most significant difference between the two monomer sys-
tems is the level of pyrene incorporation. For n-butyl acrylate
0
0
20
40
60
80
100
Percent Conversion
Fig. 2. Variation in the percent of pyrene incorporation with percent
conversion for the polymerization of 200 equivalents of styrene at 120◦C
initiated by a mixture of (18) and (19).
84%, the level of pyrene incorporation was calculated to be
14%. If the assumption[16] is made that multiple coupling
reactions giving rise to star polymers with more than one
pyrene functionality are not significant, the extent of cou-
pling for a single polymer chain or arm can be calculated
(about 1.2%). The influence of conversion on this radical–
radical coupling reaction was then examined by halting
the polymerization at conversions ranging from 6 to 84%,
isolating and purifying the star polymer, and subsequently
determining the level of pyrene incorporation. As can be
seen in Figure 2, this proved to be very instructive. A lin-
ear relationship going through the origin was not obtained;
instead, a rapid increase in the level of pyrene incorporation
was observed with approximately 10% incorporation being
obtained after only 6% conversion. The level of incorpora-
tion then increased gradually to 14% at high conversions.This
suggests that the majority of radical–radical coupling reac-
tions occur early in the polymerization, which is fully consis-
tent with the persistent radical effect proposed by Fischer.[17]
In this theory, the homolysis of a dormant species (i.e. the

780
J. Pyun et al.
this varies from 15 to 20% over the conversion range (10–
90%), which is about 50% higher than for the polymerization
of styrene. It also correlates with approximately 1.7% of the
polymerchainsundergoingcoupling.Thissuggeststhatwhile
the overall profile of the radical–radical coupling reaction is
independent of the length of the polymer chain above DP
50, the extent of the coupling reaction is dependent upon
the nature of both the monomer and propagating polymer
radicals.
In conclusion, a novel procedure based on cross coupling
between functionalized linear chains and unfunctionalized
star polymers has been developed to assess the extent of ter-
mination by radical–radical coupling in living free-radical
polymerizations. For both styrene and n-butyl acrylate it was
shown that the majority of termination by radical–radical
coupling occurs early in the polymerization process, at con-
versions of less than 10%. While the overall relationship
between termination and percent conversion is similar for
both monomers, one significant difference is that the extent
of termination is ca. 50% higher for n-butyl acrylate when
compared with styrene (1.7% versus 1.2%). This low level
of termination is consistent with the living character of the
polymerization and the proven ability to prepare block and
star copolymers. However, the values are not insignificant
and demonstrate that termination by radical–radical coupling
is an important event and should be taken into account when
complex macromolecular architectures are prepared by living
free-radical processes.
δC (400 MHz; [D6]acetone; diastereomers) 19.7, 26.3, 31.3, 62.6, 97.5,
111.1, 111.6, 133.2, 159.4, 167.3.
3,5-Bis(tetrahydropyranyloxy)benzyl alcohol (11)
To a solution of methyl 3,5-bis(tetrahydropyranyloxy)benzoate (60.0 g,
178 mmol) in dry tetrahydrofuran (800 mL) was slowly added lithium
aluminum hydride (20.0 g, 527 mmol). The gray mixture was allowed to
stir at room temperature for 1 h and was then quenched with Baekstrom’s
reagent (Na2SO4·10H2O/celite, 1 : 1 wt ratio). Solids were removed
from the reaction mixture by vacuum filtration through a coarse-grain
glass frit and the clear, colourless solution was concentrated under
vacuum. The benzyl alcohol (11) was isolated as a white solid after
recrystallization from methanol (95%) (Found: C, 66.3; H, 7.9%. Calc.
for C17H24O5: C, 66.2; H, 7.8%). δH (400 MHz; [D6]acetone; diastere-
omers) 1.54–2.10 (12 H, m), 3.55–3.60 (2 H, m), 3.82–3.94 (2 H, m),
4.60 (2 H, s), 5.50 (2 H, t), 6.61–6.65 (1 H, m), 6.71 (2 H, d, J 2.0).
δH (400 MHz; [D6]acetone; diastereomers) 19.9, 26.4, 31.5, 62.6, 65.1,
97.5, 104.9, 108.8, 146.0, 159.5.
3,5-Bis(tetrahydropyranyloxy)benzyl bromide (12)
To a solution of (11) (10.0 g, 32.4 mmol) in dichloromethane (200 mL)
was added diisopropylethylamine (6.2 mL, 35 mmol), carbon tetrabro-
mide (11.9 g, 35.8 mmol), and triphenylphosphine (9.40 g, 35.9 mmol).
The mixture was stirred at room temperature for 1 h and quenched with
deionized water (5 mL). The crude mixture was concentrated under
vacuum and purified by flash chromatography eluting with a hex-
ane/dichloromethane (4 : 1 volume ratio) solution that was gradually
increased to dichloromethane and then dichloromethane/diethyl ether
(10 : 1). Fractions collected from flash chromatography were combined
and the solvent was removed under vacuum to yield the bromide (12)
as a clear, slightly brown oil, which was used immediately (94%). δH
(400 MHz; [D6]acetone; diastereomers) 1.54–2.10 (12 H, m), 3.55–3.60
(2 H, m), 3.82–3.93 (2 H, m), 4.57 (2 H, s), 5.45 (2 H, t), 6.70–6.73 (1 H,
m), 6.79 (2 H, d, J 2.0).
Experimental
General Methods
(THP)4-[G-2]-OH (13)
Commercial reagents were obtained from Aldrich and used with-
out further purification. The synthesis of 2,2,5-trimethyl-3-(1-
(4ꢀ-chloromethyl)phenylethoxy)-4-phenyl-3-azahexane was conducted
using previously reported methods.[19] Analytical TLC was performed
on commercial Merck plates coated with silica gel GF254 (0.24 mm
thick). Silica gel for flash chromatography was Merck Kieselgel 60
(230–400 mesh, ASTM). NMR studies were performed on a Bruker
AVANCE 400 FT-NMR spectrometer using deuterated solvents and the
solvent peak as a reference. Gel permeation chromatography was per-
formed in tetrahydrofuran (THF) on a Waters chromatograph equipped
with four 5 µm Waters columns (300 × 7.7 mm) connected in series
with increasing pore size (100, 1000, 100 000, 1 000 000 Å). A Waters
410 differential refractometer and a 996 photodiode array detector were
employed. The polystyrene molecular weights were calculated rela-
tive to linear polystyrene standards, whereas the poly(n-butyl acrylate)
molecular weights were calculated relative to poly(n-butyl acrylate)
standards.
To a solution of (12) (17.9 g, 48.1 mmol) and 3,5-dihydroxybenzyl alco-
hol (3.20 g, 23.0 mmol) in dry acetone (250 mL) was added [18]crown-
6 (126 mg, 0.48 mmol) and anhydrous potassium carbonate (9.8 g,
72 mmol). The suspension was stirred vigorously under an argon atmo-
sphere and refluxed for 24 h. The crude product was purified by flash
chromatography eluting with dichloromethane, gradually increasing to
dichloromethane/diethyl ether (10 : 1). Fractions collected from flash
chromatography were combined and the solvent was removed under
vacuum to give the second-generation dendrimer (13) as a white foam
(93%)(Found:C, 68.1;H, 7.5%. Calc. forC41H52O11:C, 68.3;H, 7.3%).
δH (400 MHz; CDCl3; diastereomers) 1.54–2.10 (24 H, m), 3.55–3.60
(4 H, m), 3.84–3.93 (4 H, m), 4.60 (2 H, s), 4.90 (12 H, s), 5.27–5.42
(4 H, m), 6.50 (1 H, m), 6.60 (2 H, d, J 2.0), 6.75 (2 H, m), 6.80 (4 H,
d, J 2.0). δC ([D6]acetone; diastereomers) 19.9, 26.4, 31.5, 62.6, 68.5,
70.6, 97.5, 101.5, 105.7, 106.3, 109.8, 140.8, 146.4, 159.7, 161.3.
(THP)4-[G-2]-Br (14)
Methyl 3,5-Bis(tetrahydropyranyloxy)benzoate
The same general procedure was employed as for the synthe-
sis of (12) using the second-generation alcohol (13). Purification
was performed using flash chromatography eluting first with light
petroleum/dichloromethane (1 : 1), then dichloromethane, and finally
dichloromethane/diethyl ether (10 : 1). Fractions collected from flash
chromatography were combined and the solvent was removed under
vacuum to yield the bromo derivative (14) as a colourless glass (90%)
(Found: C, 63.0; H, 6.5%. Calc. for C41H51BrO10: C, 62.8; H, 6.6%).
δH (400 MHz; CDCl3; diastereomers) 1.54–2.10 (24 H, m), 3.55–3.60
(4 H, m), 3.84–3.93 (4 H, m), 4.35 (2 H, s), 4.90 (12 H, s), 5.27–5.42
(4 H, m), 6.50 (1 H, m), 6.60 (2 H, d, J 2.0), 6.75 (2 H, m), 6.80 (4 H, d,
J 2.0).
To a stirred suspension of methyl 3,5-dihydroxybenzoate (40.0 g,
239 mmol) in dichloromethane (400 mL) was added 3,4-dihydro-
2H-pyran (80.0 g, 952 mmol) followed by 12 drops of concentrated
hydrochloric acid (38 wt-%). The reaction mixture was allowed to stir
for 18 h and the solution was then concentrated under reduced pressure,
loaded onto a silica column and purified by flash chromatography elut-
ing with a mixture of hexane and acetone (20 : 1 volume ratio). Fractions
collectedfromflashchromatographywerecombinedandthesolventwas
removed under vacuum to give the ester as a white solid (92%) (Found:
C, 64.4; H, 7.0; Calc. for C18H24O6: C, 64.3; H, 7.2%). δH (400 MHz;
[D6]acetone; diastereomers) 1.54–2.10 (12 H, m), 3.60 (2 H, m), 3.80
(2 H, m), 3.90 (3 H, s), 5.50 (2 H, t), 7.00 (1 H, m), 7.30 (2 H, d, J 2.0).

Evaluating the Effect of Termination in Living Free-Radical Polymerizations
781
(THP)12-([G-2])3-C (16)
light petroleum/dichloromethane (8 : 2) to give the labelled derivative
(19) as a light-yellow gum (84%) (Found: C, 84.6; H, 7.9; N, 2.5%.
Calc. for C43H49NO2: C, 84.4; H, 8.1; N, 2.3%). δH (400 MHz; CDCl3;
both diastereomers) 0.22 (3 H, d, J 6.5), 0.54 (3 H, d, J 6.5), 0.77 (9 H,
s), 0.92 (3 H, d), 1.04 (9 H, s), 1.31 (3 H, d, J 6.30), 1.54 (3 H, d, J 7.0),
1.62 (3 H, d, J 6.80), 1.70 (2 H, 2 × m), 2.35 (2 H, 2 × m), 3.40 (4 H,
2 × m), 3.41 (1 H, d, J 10.8), 4.50 (4 H, d, J 7.5), 4.95 (2 H, 2 × q, J
6.5), 7.10–7.50 (18 H, m), 7.70–8.20 (18 H, m). δC (100 MHz; CDCl3;
both diastereomers) 21.2, 21.2, 22.0, 22.2, 23.2, 24.7, 28.3, 28.5, 29.9,
29.9, 31.7, 32.1, 33.3, 60.5, 60.6, 70.1, 70.3, 72.9, 72.9, 82.5, 83.4,
123.5, 124.7, 125.1, 125.2, 125.8, 126.3, 126.4, 126.6, 127.1, 127.2,
127.3, 127.4, 127.5, 127.6, 128.7, 129.8, 131.0, 131.1, 131.5, 136.9,
137.6, 142.3, 142.5, 144.4, 145.1.
Toasolutionof(14)(10.80g, 13.83mmol), 1,1,1-tris(4ꢀ-hydroxyphenyl)-
ethane, and (15) (1.28 g, 4.19 mmol) in dry acetone (100 mL) was added
[18]crown-6 (0.10 g, 0.37 mmol) and anhydrous potassium carbonate
(5.0 g, 36 mmol). The suspension was stirred vigorously under an argon
atmosphere and refluxed for 24 h. The crude product was purified by
flash chromatography eluting with dichloromethane, gradually increas-
ing to dichloromethane/diethyl ether (19 : 1). Fractions collected from
flash chromatography were combined and the solvent was removed
under vacuum to give the THP-protected dendrimer (16) as a white
foam (67%) (Found: C, 71.3; H, 6.9%. Calc. for C143H168O33: C, 71.1;
H, 7.0%). δH (400 MHz; CDCl3; diastereomers) 1.54–2.10 (72 H, m),
2.15 (3 H, s), 3.55–3.60 (12 H, m), 3.84–3.93 (12 H, m), 4.95 (18 H, s),
5.27–5.42 (12 H, m), 6.54–6.55 (3 H, m), 6.60 (6 H, d, J 2.0), 6.75 (6 H,
m), 6.80 (12 H, d, J 2.0), 6.90 (6 H, d, J 8.0), 7.00 (6 H, d, J 8.0). δC
([D6]acetone; diastereomers) 19.9, 26.4, 31.5, 62.6, 70.8, 97.5, 100.9,
105.7, 107.8, 110.0, 140.6, 141.3, 143.3, 158.1, 159.7, 161.4.
General Procedure for the Nitroxide-Mediated Polymerization of
Styrene Using a Mixture of the Dendritic Initiator (18) and the
Pyrene-Labelled Alkoxyamine (19)
A mixture of styrene (13.5 g, 130 mmol, 200 equivalents), the
dodeca-initiator (18) (100 mg, 0.018 mmol), and the pyrene-labelled
alkoxyamine (19) (265 mg, 0.435 mmol) were weighed into a vial that
contained a magnetic stir bar. The vial was degassed by three freeze–
pump–thaw cycles and sealed under argon. The sealed vials were heated
at 120◦C for an appropriate reaction time, dissolved in dichloromethane,
and purified by precipitation in methanol (three times).The star polymer
was obtained by prepratory GPC eluting with THF, and was analyzed
by SEC, NMR, and UV/vis.
(HO)12-([G-2])3-C (17)
To a solution of (16) (7.40 g, 3.12 mmol) in a mixture of tetrahydro-
furan (100 mL) and methanol (50 mL) was added p-toluenesulfonic
acid monohydrate (70 mg, 0.37 mmol). The reaction mixture was then
allowed to stir at room temperature for 3 h before being quenched
with sodium bicarbonate and purified by flash chromatography eluting
with dichloromethane followed by dichloromethane/methanol (4 : 1).
Fractions collected from flash chromatography were combined and the
solvent was removed under vacuum to yield the dodecaphenol (17) as a
colourless glass (61%) (Found: C, 67.5; H, 5.1%. Calc. for C83H72O25
:
General Procedure for Nitroxide-Mediated Polymerization of
Acrylates Using a Mixture of the Dendritic Initiator (18) and
the Pyrene-Labelled Alkoxyamine (19)
C, 67.8; H, 4.9%). δH (400 MHz, [D4]MeOH) 2.05 (3 H, s), 4.85–4.86
(18 H, overlapping singlets), 6.18–6.19 (6 H, m), 6.35 (12 H, d, J 2.0),
6.49 (3 H, m), 6.61 (6 H, d, J 2.0), 6.78 (6 H, d, J 8.0), 6.92 (6 H, d,
J 8.0). δC ([D6]acetone) 31.3, 70.8, 101.4, 107.4, 115.3, 130.9, 141.0,
141.3, 143.3, 158.5, 160.0, 161.5.
A mixture of n-butyl acrylate (16.64 g, 130 mmol, 200 equivalents),
the dodeca-initiator (18) (100 mg, 0.018 mmol), the pyrene-labelled
alkoxyamine (19) (265 mg, 0.435 mmol), and the free nitroxide (8.5 mg,
0.033 mmol, 0.05 equivalents) were weighed into a vial that contained
a magnetic stir bar. The vial was degassed by three freeze–pump–thaw
cycles and sealed under argon.The sealed vials were heated at 120◦C for
an appropriate reaction time, dissolved in dichloromethane, and purified
by precipitation in methanol (three times).The star polymer was isolated
by preparatory GPC eluting withTHF, and was analyzed by SEC, NMR,
and UV/vis.
General Procedure for the Alkylation of Phenol-Terminated
Dendrimers with 2,2,5-Trimethyl-3-(1-(4ꢀ-
chloromethyl)phenylethoxy)-4-phenyl-3-azahexane
(Alk)12-([G-2])3-C (18)
To a solution of (17) (1.30 g, 0.88 mmol) and the chloromethyl-
substituted alkoxyamine (6) (4.57 g, 14.7 mmol) in dry acetone (50 mL)
was added [18]crown-6 (0.10 g, 0.38 mmol) and potassium carbon-
ate (4.0 g, 29 mmol). The suspension was stirred vigorously under an
argon atmosphere and refluxed for 24 h. The reaction mixture was
then cooled to room temperature, evaporated to dryness, partitioned
between water (200 mL) and dichloromethane (200 mL), and the aque-
ous layer extracted with dichloromethane (2 × 100 mL). The combined
organic extracts were then dried and evaporated to dryness. Purifica-
tion of the crude product was performed using flash chromatography
eluting with dichloromethane/diethyl ether (50 : 1). Fractions collected
from flash chromatography were combined and the solvent was removed
under vacuum to give the multifunctional alkoxyamine initiator (18)
as a gummy solid (72%) (Found: C, 78.3; H, 8.3; N, 3.1%. Calc. for
C359H444N12O37: C, 78.1; H, 8.1; N, 3.1%). δH (400 MHz; CDCl3)
0.02 (36 H, d, J 6.5), 0.30 (36 H, d, J 6.5), 0.57 (108 H, s), 0.70 (36 H,
d, J 6.5), 0.83 (108 H, s), 1.10 (36 H, d, J 6.5), 1.31 (36 H, d, J 6.5), 1.40
(36 H, d, J 6.5), 1.90 (3 H, s), 2.12–2.14 (12 H, m), 3.07–3.20 (12 H,
2 × d, J 12.0), 4.70–4.83 (78 H, m), 6.32–7.25 (75 H, m).
Acknowledgments
Financial support from the MRSEC Program of the National
Science Foundation under Award Number DMR-9808677,
the Center for Polymeric Interfaces and Macromolecular
Assemblies, the NIRT Program of the National Science Foun-
dation Grant No. 0210247, IBM Corporation, DOE-BES, and
AFOSR is gratefully acknowledged.
References
[1] (a) C. J. Hawker, A. W. Bosman, E. Harth, Chem. Rev. 2001,
101, 3661. (b) T. Tsoukatos, S. Pispas, N. Hadjichristidis,
J. Polym. Sci., Part A: Polym. Chem. 2001, 39, 320. (c) A.
J. Pasquale, T. E. Long, J. Polym. Sci., Part A: Polym. Chem.
2001, 39, 216. (d) P. Moschogianni, S. Pispas, N. Hadjichristidis,
J. Polym. Sci., Part A: Polym. Chem. 2001, 39, 650. (e) C.
Farcet, J. Nicolas, B. Charleux, J. Polym. Sci., Part A: Polym.
Chem. 2002, 40, 4410. (f ) H. Götz, E. Harth, S. M. Schiller,
C. W. Frank, W. Knoll, C. J. Hawker, J. Polym. Sci., Part
A: Polym. Chem. 2002, 40, 3379. (g) M. F. Cunningham,
K. Tortosa, M. Lin, B. Keoshkerian, M. K. Georges, J. Polym.
Sci., Part A: Polym. Chem. 2002, 40, 2828. (h) S. Blomberg,
S. Ostberg, E. Harth, A. W. Bosman, B. Van Horn, C. J.
Hawker, J. Polym. Sci., Part A: Polym. Chem. 2002, 40, 1309.
(i) S. P. Cresidio, F. Aldabbagh, W. K. Busfield, I. D. Jenkins,
4-(4ꢀ-Pyrenebutoxymethyl)-2,2,5-trimethyl-3-(1-phenylethoxy)-4-
phenyl-3-azahexane (19)
4-Pyrene butanol (2.20 g, 8.03 mmol) was dissolved in dryTHF (50 mL)
under an argon atmosphere. Sodium hydride (200 mg, 8.41 mmol)
was added and the reaction mixture was stirred at room temperature
for 30 min. The chloromethyl alkoxyamine (6) (3.04 g, 8.10 mmol)
was added and the reaction was refluxed 16 h under argon. The
reaction mixture was then evaporated to dryness, extracted with
dichloromethane, washed with water, dried, filtered, and concentrated.
The crude product was purified by flash chromatography eluting with

782
J. Pyun et al.
S. H. Thang, C. Zayas-Holdsworth, P. B. Zetterlund, J. Polym.
Sci., Part A: Polym. Chem. 2001, 39, 1232.
2003, 36, 605. (c) N. B. Bowden, M. Dankova, W. Wiyatno,
C. J. Hawker, R. M. Waymouth, Macromolecules 2002, 35,
9246. (d) D. Mecerreyes, G. Moineau, P. Dubois, R. Jerome,
J. L. Hedrick, C. J. Hawker, E. E. Malmstrom, M. Trollsas,
Angew. Chem. Int. Ed. 1998, 37, 1274. (e) J. F. Quinn,
R. P. Chaplin, T. P. Davis, J. Polym. Sci., Part A: Polym.
Chem. 2002, 40, 2956. (f ) V. Percec, F. Asgarzadeh, J. Polym.
Sci., Part A: Polym. Chem. 2001, 39, 1120.
[2] (a) K. Matyjaszewski, J. Xia, Chem. Rev. 2001, 101, 2921. (b)
M. Kamigaito, T. Ando, M. Sawamoto, Chem. Rev. 2001, 101,
3689. (c) A. P. Smith, C. L. Fraser, J. Polym. Sci., Part A: Polym.
Chem. 2002, 40, 4250. (d) T. Sarbu, T. Pintauer, B. McKenzie,
K. Matyjaszewski, J. Polym. Sci., Part A: Polym. Chem. 2002,
40, 3153. (e) A. P. Narrainen, S. Pascual, D. M. Haddleton,
J. Polym. Sci., Part A: Polym. Chem. 2002, 40, 439. (f )
M. L. Becker, E. E. Remsen, K. L. Wooley, J. Polym. Sci., Part
A: Polym. Chem. 2001, 39, 4152. (g) A. D. Asandei, V. Percec,
J. Polym. Sci., Part A: Polym. Chem. 2001, 39, 3392.
[3] (a) R. T. A. Mayadunne, E. Rizzardo, J. Chiefari, J. Krstina,
G. Moad, A. Postma, S. H. Thang, Macromolecules 2000, 33,
243. (b) S. W. Prescott, M. J. Ballard, E. Rizzardo, R. G. Gilbert,
Macromolecules 2002, 35, 5417. (c) A. Goto, K. Sato, Y. Tsujii,
T. Fukuda, G. Moad, E. Rizzardo, S. H. Thang, Macromolecules
2001, 34, 402. (d) C. Barner-Kowollik, T. P. Davis, J. P. A. Heuts,
M. H. Stenzel, P. Vana, M. Whittaker, J. Polym. Sci., Part A:
Polym. Chem. 2003, 41, 365. (e) L. Barner, N. Zwaneveld,
S. Perera, Y. Pham, T. P. Davis, J. Polym. Sci., Part A: Polym.
Chem. 2002, 40, 4180. (f ) S. C. Farmer, T. E. Patten, J. Polym.
Sci., Part A: Polym. Chem. 2002, 40, 555. (g) M. J. Monteiro,
R. Bussels, T. S. Wilkinson, J. Polym. Sci., Part A: Polym.
Chem. 2001, 39, 2813.
[9] (a) M. R. Leduc, C. J. Hawker, J. Dao, J. M. J. Fréchet,
J. Am. Chem. Soc. 1996, 118, 11 111. (b) D. J. Pochan,
L. Pakstis, E. Huang, C. J. Hawker, R. Vestberg, J. Pople,
Macromolecules 2002, 35, 9239. (c) M. E. Mackay, Y. Hong,
M. Jeong, B. M. Tande, N. J. Wagner, S. Hong, S. P. Gido,
R. Vestberg, C. J. Hawker, Macromolecules 2002, 35, 8391.
[10] It has previously been shown using functionalized alkoxyamines
and a crossover strategy that efficient exchange of the persistent
nitroxide radicals occurs very early in the polymerization.
C. J. Hawker, G. G. Barclay, J. Dao, J. Am. Chem. Soc. 1996,
118, 11467.
[11] (a) C. J. Hawker, P. J. Farrington, M. E. Mackay, K. L. Wooley,
J. M. J. Fréchet, J. Am. Chem. Soc. 1995, 117, 4409. (b)
K. L. Wooley, C. J. Hawker, J. M. Pochan, J. M. J. Frechet,
Macromolecules 1993, 26, 1514. (c) T. H. Mourey, S. R. Turner,
M. Rubinstein, J. M. J. Fréchet, C. J. Hawker, K. L. Wooley,
Macromolecules 1992, 25, 2401.
[4] (a) T. Kato, Science 2002, 295, 2414. (b) S. M. Yu, C. M. Soto,
D. A. Tirrell, J. Am. Chem. Soc. 2000, 122, 6552. (c)
H. W. I. Peerlings, R. A. T. M. Van Benthem, E. W. Mei-
jer, J. Polym. Sci., Part A: Polym. Chem. 2001, 39, 3112. (d)
T. Nishinaga, A. Tanatani, K. Oh, J. S. Moore, J. Am. Chem.
Soc. 2002, 124, 5934. (e) V. Percec, W. D. Cho, G. Ungar,
D. J. P. Yeardley, Angew. Chem. Int. Ed. 2000, 39, 1597. (f )
H. Ma, A. K. Y. Jen, Adv. Mater. 2001, 13, 1201. (g) Q. Ma,
E. E. Remsen, T. Kowalewski, K. L. Wooley, J. Am. Chem.
Soc. 2001, 123, 4627. (h) J. M. Nam, S. J. Park, C. A. Mirkin,
J. Am. Chem. Soc. 2002, 124, 3820. (i) E. Zubarev, S. I. Stupp,
J. Am. Chem. Soc. 2002, 124, 5762. (j) T. Weil, U. M. Wiesler,
A. Herrmann, R. Bauer, J. Hofkens, F. De Schryver, K. Müllen,
J. Am. Chem. Soc. 2001, 123, 8101.
[12] (a) C. J. Hawker, J. M. J. Fréchet, J. Am. Chem. Soc. 1990,
112, 7638. (b) C. J. Hawker, J. M. J. Fréchet, J. Chem. Soc.,
Chem. Commun. 1990, 1010.
[13] D. A. Tomalia, J. M. J. Fréchet, J. Polym. Sci., Part A: Polym.
Chem. 2002, 40, 2719. (b) H. W. I. Peerlings, R. A. T. M. Van
Benthem, E. W. Meijer, J. Polym. Sci., Part A: Polym. Chem.
2001, 39, 3112.
[14] M. Rodlert, E. Harth, I. Rees, C. J. Hawker, J. Polym. Sci.,
Part A: Polym. Chem. 2000, 38, 4749.
[15] A 1 : 24 molar ratio of the dodeca-initiator (18) to the pyrene-
labelled initiator (19) was employed. In terms of the ratio of
alkoxyamine groups, this represents a 1 : 2 ratio of alkoxyamine
groups for (18) (12 alkoxyamine groups per molecule) compared
with (19) (1 alkoxyamine group per molecule.)
[5] C. J. Hawker, Angew Chem. Int. Ed. Engl. 1995, 34, 1456.
[6] (a) A. W. Bosman, R. Vestberg, A. Heumann, J. M. J. Frechet,
C. J. Hawker, J. Am. Chem. Soc. 2003, 125, 715. (b) M. Yoo,
A. Heize, J. L. Hedrick, R. D. Miller, C. W. Frank, Macro-
molecules 2003, 36, 268. (c) M. H. Stenzel, T. P. Davis, J. Polym.
Sci., Part A: Polym. Chem. 2002, 40, 4498. (d) K.-Y. Baek,
M. Kamigaito, M. Sawamoto, J. Polym. Sci., Part A:
Polym. Chem. 2002, 40, 2245. (e) D. R. Robello, A. Andre,
T.A. McCovick,A. Krausx, T. H. Mourey, Macromolecules 2002,
35, 9334. (f ) K. Ohno, B. Wong, D. M. Haddleton, J. Polym.
Sci., Part A: Polym. Chem. 2001, 39, 2206. (g) P. Moschogianni,
S. Pispas, N. Hadjichristidis, J. Polym. Sci., Part A: Polym.
Chem. 2001, 39, 4152. (h) K. Matyjaszewski, P. J. Miller,
J. Pyun, G. Kickelbick, S. Diamanti, Macromolecules 1999, 32,
6526. (j) C. J. Hawker, Acc. Chem. Res. 1997, 30, 373.
[7] (a) S. G. Gaynor, S. Edelman, K. Matyjaszewski, Macro-
molecules 1996, 29, 1079, 6526. (b) C. J. Hawker,
J. M. J. Fréchet, R. B. Grubbs, J. Dao, J. Am. Chem. Soc. 1995,
117, 10 763. (c) M. W. Weimer, I. Gitsov, J. M. J. Fréchet,
J. Polym. Sci., Part A: Polym. Chem. 1998, 36, 955.
[16] While coupling of two or more linear chains to the star
polymer leading to a multiply-functionalized star is statistically
possible, the low occurrence of monofunctionalization makes
the incorporation of two or more pyrene functionalities unlikely.
Therefore, in the calculation of the relative percentage of pyrene
functionalized star polymers only mono-addition was considered.
Additionally, intramolecular termination between arms within
the star polymer is not considered.
[17] H. Fischer, Chem. Rev. 2001, 101, 3581.
[18] (a) G. S. Ananchenko, M. Souaille, H. Fischer, C. LeMercier,
P. Tordo, J. Polym. Sci., Part A: Polym. Chem. 2002, 40, 3264.
(b) G. S. Ananchenko, H. Fischer, J. Polym. Sci., Part A:
Polym. Chem. 2001, 39, 3604. (c) M. Souaille, H. Fischer,
Macromolecules 2001, 34, 2830. (d) M. Souaille, H. Fischer,
Macromolecules 2000, 33, 7378.
[19] (a) D. Benoit, V. Chaplinski, R. Braslau, C. J. Hawker, J. Am.
Chem. Soc. 1999, 121, 3904. (b) J. Dao, D. Benoit, C. J. Hawker,
J. Polym. Sci., Part A: Polym. Chem. 1998, 36, 2161.
[8] (a) K. L. Beers, S. G. Gaynor, K. Matyjaszewski, S. S. Sheiko,
M. Moeller, Macromolecules 1998, 31, 9413. (b) S. Qin,
K. Matyjaszewski, H. Xu, S. S. Sheiko, Macromolecules