Prop-2-yn-1-yl 2-Bromo-2-methylpropanoate: Identification and Suppression of Side Reactions of a Commonly Used Terminal Alkyne-Functional ATRP Initiator

Article abstract of DOI:10.1021/acs.macromol.5b00652

The atom transfer radical polymerization (ATRP) of styrene was investigated using the popular alkyne-functional initiator prop-2-yn-1-yl 2-bromo-2-methylpropanoate (PBiB). The polymerization kinetics and evolution of molecular weight as a function of monomer conversion were systematically studied with PBiB and similar initiators with protecting groups at the reactive propargylic and terminal acetylenic sites. These studies were compared to control studies using the nonfunctional initiator ethyl 2-bromoisobutyrate. As confirmed by NMR analysis of a model reaction, the terminal alkynes undergo oxidative alkyne-alkyne coupling under ATRP conditions, resulting in polymers with bimodal molecular weight distributions. This side reaction is significant because it diminishes the orthogonality of ATRP/copper-catalyzed azide-alkyne cycloaddition procedures as well as the control of ATRP.

Full text of DOI:10.1021/acs.macromol.5b00652

Article
pubs.acs.org/Macromolecules
Prop-2-yn-1-yl 2‑Bromo-2-methylpropanoate: Identification and
Suppression of Side Reactions of a Commonly Used Terminal Alkyne-
Functional ATRP Initiator
William K. Storms-Miller and Coleen Pugh*
Department of Polymer Science, The University of Akron, Akron, Ohio 44325-3909, United States
*
S Supporting Information
ABSTRACT: The atom transfer radical polymerization (ATRP) of styrene was investigated using the popular alkyne-functional
initiator prop-2-yn-1-yl 2-bromo-2-methylpropanoate (PBiB). The polymerization kinetics and evolution of molecular weight as
a function of monomer conversion were systematically studied with PBiB and similar initiators with protecting groups at the
reactive propargylic and terminal acetylenic sites. These studies were compared to control studies using the nonfunctional
initiator ethyl 2-bromoisobutyrate. As confirmed by NMR analysis of a model reaction, the terminal alkynes undergo oxidative
alkyne−alkyne coupling under ATRP conditions, resulting in polymers with bimodal molecular weight distributions. This side
reaction is significant because it diminishes the orthogonality of ATRP/copper-catalyzed azide−alkyne cycloaddition procedures
as well as the control of ATRP.
INTRODUCTION
Scheme 1. Known Side Reactions of Terminal Alkynes That
May Occur under ATRP Conditions
■
Atom transfer radical polymerization (ATRP) is a well-
established and very popular polymerization method that
enables the synthesis of diverse polymer architectures with well-
controlled molecular weights and narrow molecular weight
1
,2
distributions.
ATRP tolerates many functional groups,
thereby facilitating the preparation of highly functionalized
3
polymers. In addition to main-chain functional polymers
prepared by the polymerization of functional monomers,
telechelic polymers have been produced using functional
4
5
initiators or by functionalization of the halogen chain end.
Because of the functional group tolerance of ATRP and the
rapid growth in the use of copper-catalyzed azide−alkyne
cycloadditions (CuCAAC), ATRP has been used extensively to
produce polymers with azide- and alkyne-functional groups,
6
−10
either at the chain ends
polymer backbone.
or as pendant groups along the
1
1,12
Although CuCAAC and radical polymerization chemistries
are often treated as orthogonal, neither azides nor terminal
alkynes are totally inert to radicals and/or the conditions used
for radical polymerizations. For example, 2-azidoethyl meth-
acrylate dimerizes to form a triazoline ring under reversible
addition−fragmentation chain transfer (RAFT) polymerization
1
9
13
addition across the triple bond, and chain transfer of the
20
conditions, even at relatively low temperature (50 °C).
radical with propargylic atoms, under conditions that may
exist in conventional and/or “controlled” radical polymer-
izations. Alkyne-functional monomers also participate in side
reactions during radical polymerizations that result in cross-
Similarly, alkyl azides undergo a 1,3-dipolar cycloaddition with
many electron-deficient olefins, such as N-isopropylacrylamide,
dimethylacrylamide, methyl acrylate, and methyl methacrylate,
under RAFT polymerization conditions, to form triazoles and
1
4
aziridines.
As outlined in Scheme 1, terminal alkynes participate in a
Received: April 1, 2015
Revised: May 13, 2015
Published: June 1, 2015
variety of reactions, including oxidative alkyne−alkyne
1
5−17,17
18
coupling,
formation of cuprous acetylides, radical
©
2015 American Chemical Society
3803
DOI: 10.1021/acs.macromol.5b00652
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Macromolecules
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Scheme 2. Control Initiator, Ethyl 2-Bromoisobutyrate (EBiB), and Alkyne-Functional Initiators Used in This Study: Prop-2-
yn-1-yl 2-Bromo-2-methylpropanoate (PBiB), 2-Methylbut-3-yn-2-yl 2-Bromo-2-methylpropanoate (MBBiB), and 3-
(Trimethylsilyl)prop-2-yn-1-yl 2-Bromo-2-methylpropanoate (TMSPBiB)
1
1,21,22
linked polymers,
which necessitates the use of low
β-vinyl resonances (5.23 and 5.75 ppm) of styrene relative to that of
2
3
the methoxy resonance (3.80 ppm) of anisole, which was used as an
temperature and/or protection of the terminal acetylenic
1
13
1
2,24
internal standard. H (300 or 500 MHz) and C NMR (75 or 125
MHz) NMR spectra (δ, ppm) were recorded on either a Varian
Mercury 300 spectrometer or a Varian 500 spectrometer, respectively.
site.
Nevertheless, alkyne-functionalized ATRP initiators
and RAFT chain-transfer agents have been used extensively,
with these known side reactions mostly ignored or dismissed
due to the intrinsically low concentration of the resulting chain
ends. Occasionally the acetylenic position of terminal alkyne-
functionalized ATRP initiators and RAFT chain-transfer agents
are protected using a silicon-protecting group in order to
2
-D NMR spectra were recorded on the Varian 500 spectrometer.
Unless noted otherwise, all spectra were recorded in CDCl , and the
3
resonances were measured relative to residual solvent resonances and
referenced to tetramethylsilane (0.0 ppm).
Number-average (M ) and weight-average (M ) molecular weights
n
w
25
prevent “copper complexation” or cuprous acetylide for-
mation and other unspecified “side reactions”.
relative to linear polystyrene (GPCPSt) and polydisperisties (Đ = M /
w
8
,26−29
M ) were determined by gel permeation chromatography (GPC) from
n
calibration curves of log M vs elution volume at 35 °C using THF as
This paper investigates the possible side reactions involving
one of the most popular alkyne-functional ATRP initiators,
prop-2-yn-1-yl 2-bromo-2-methylpropanoate (PBiB), by com-
paring its ATRP polymerization of styrene to that of an
analogous initiator without an alkyne group, ethyl 2-
bromoisobutyrate (EBiB), as the control (Scheme 2). These
results are further compared to the ATRP polymerizations of
styrene initiated by alkyne-functional initiators that have
protecting groups at either the propargylic position (2-
methylbut-3-yn-2-yl 2-bromo-2-methylpropanoate = MBBiB)
or the terminal acetylenic site (3-(trimethylsilyl)prop-2-yn-1-yl
n
solvent (1.0 mL/min), a guard column and a set of 50, 100, 500, and
4
4
1
4
0 Å as well as linear (50−10 Å) Styragel 5 μm columns, a Waters
86 tunable UV/Vis detector set at 254 nm, a Waters 410 differential
refractometer, and Millenium Empower 3 software. All samples were
passed through basic activated alumina to remove copper catalysts
prior to injection into the GPC.
Synthesis of 2-Methylbut-3-yn-2-yl 2-Bromo-2-methylpro-
panoate (MBBiB). Because of the steric hindrance of both the
electrophile and nucleophile, a large excess of the nucleophile was
used, including as the solvent for the addition, to increase the rate of
reaction. A solution of 2-bromoisobutyryl bromide (2.0 mL, 16 mmol)
in 2-methyl-3-butyn-2-ol (5 mL, 50 mmol) was slowly added dropwise
to an ice-cooled solution of DMAP (0.18 g, 1.5 mmol) and
triethylamine (2.3 mL, 17 mmol) in 2-methyl-3-butyn-2-ol (5 mL,
2
-bromo-2-methylpropanoate = TMSPBiB). We then offer a
route to suppress the side reactions of alkyne-functional
initiators in order to prepare highly functional polystyrenes
with controlled molecular weights and narrow molecular weight
distributions.
5
0 mmol). The reaction mixture was stirred at room temperature for
22 h and then concentrated by rotary evaporation. The concentrate
was diluted with CH Cl (20 mL) and washed sequentially with 1.5 M
2
2
aqueous HCl (10 mL), saturated aqueous NaHCO (10 mL), and
3
saturated aqueous NaCl (10 mL), and then dried over MgSO . After
4
EXPERIMENTAL SECTION
Materials. Anisole (Aldrich, 99.7%), benzene-d6 (Cambridge
Isotopes, 99.5%), 2-bromoisobutyryl bromide (Aldrich, 98%), cupric
bromide (Aldrich, 99%), and 4-(dimethylamino)pyridine (Aldrich,
9%) (DMAP) were used as received. Cuprous bromide (Alfa Aesar,
8%) was stirred with acetic acid, washed with diethyl ether, and dried
under vacuum. Diethyl ether (Fischer) was distilled from purple
sodium benzophenone ketyl. Ethyl 2-bromoisobutyrate (Aldrich, 98%)
was distilled under reduced pressure. Reagent grade methylene
■
filtration and removing the solvent by rotary evaporation, the crude
product was distilled, collecting the fraction boiling at 75−77 °C/10
mmHg to yield 2.1 g (56%) of 2-methylbut-3-yn-2-yl 2-bromo-2-
1
methylpropanoate as a colorless oil. H NMR (300 MHz): 1.72 (s,
1
3
9
9
C(CH ) O), 1.92 (s, C(CH ) Br), 2.56 (s, HCC). C NMR (75
3
2
3 2
MHz): 28.6 (C(CH ) O, 30.7 (C(CH ) Br), 56.6 (C(CH ) Br), 72.9
3
2
3
2
3 2
(
HCC), 73.3 (C(CH ) O), 84.1 (HCC), 169.7 (CO).
3
2
Synthesis of 3-(Trimethylsilyl)prop-2-yn-1-yl 2-Bromo-2-
methylpropanoate (TMSPBiB). A solution of 2-bromoisobutyryl
bromide (2.3 mL, 0.19 mol) in diethyl ether (5 mL) was added
dropwise over 30 min to an ice-cooled solution of 3-(trimethylsilyl)-
prop-2-yn-1-ol (2.0 g, 0.16 mol) and triethylamine (1.6 g, 0.15 mol) in
diethyl ether (10 mL). The reaction mixture was stirred at room
temperature for 23 h. Precipitated triethylammonium bromide was
removed by filtration through a fritted glass funnel, and the solvent
was removed from the filtrate by rotary evaporation. The orange
residue was distilled (55−57 °C/1 mmHg), and the resulting orange
distillate was passed through a plug of basic activated alumina using
hexanes/ethyl acetate (10:1) as the eluant to remove residual 2-
bromoisobutyric acid. Solvent was removed by rotary evaporation and
then by drying under vacuum on a Schlenk line to yield 3.1 g (72%) of
chloride was dried over CaH and distilled. 2-Methyl-3-butyn-2-ol
2
(
Aldrich, 98%) was dried over 4 Å molecular sieves and distilled.
N,N,N′,N″,N″-Pentamethyldiethylenetriamine (Aldrich, 99%)
PMDETA) was dried over K CO and distilled under reduced
(
2
3
pressure. Propargyl acetate was synthesized in 57% yield by
esterification of acetyl chloride with propargyl alcohol (Supporting
Information). Prop-2-yn-1-yl 2-bromo-2-methylpropanoate (PBiB)
and 3-(trimethylsilyl)propargyl alcohol were synthesized according
to literature procedures. Styrene (Aldrich, 99%) was passed through
basic alumina and distilled from CaH2 under reduced pressure.
Reagent grade tetrahydrofuran (THF) was distilled from purple
sodium benzophenone ketyl. Triethylamine (Aldrich, 99%) was dried
over KOH and distilled.
3
0
31
1
TMSPBiB as a colorless oil. H NMR (500 MHz): 0.19 (s, Si(CH ) ),
3
3
13
Techniques. All reactions were performed under a N atmosphere
1.96 (s, CBr(CH ) ), 4.76 (s, CH ). C NMR (125 MHz): −0.2
2
3
2
2
using a Schlenk line unless noted otherwise. The kinetic experiments
for the polymerizations were performed in triplicate in 20 mL screw-
capped vials, which were assembled in a Vacuum Atmospheres drybox
(Si(CH ) , 30.9 (CBr(CH ) ), 54.4 (CH ), 55.3 (CBr(CH ) ), 92.9
3 3 3 2 2 3 2
(SiCC), 98.4 (SiCC), 171.0 (CO).
Reaction of Prop-2-yn-1-yl 2-Bromo-2-methylpropanoate
with the ATRP Catalyst System in the Absence of Monomer. A
solution of PBiB (60 mg, 0.30 mmol) and PMDETA (56 mg, 0.32
under a N atmosphere. The monomer conversions were measured by
2
1
H NMR spectroscopy by following the changes in the integral of the
3
804
DOI: 10.1021/acs.macromol.5b00652
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Table 1. Polymerization Results from the Atom Transfer Radical Polymerizations of Styrene (St) at 110 °C Using the 2-
a
Bromoisobutyrate Initiators Shown in Scheme 2
corresponding to Figure 1
corresponding to Figure 2
corresponding to Figures 5 and 6
kpapp × 10 (s−1)
4
M /p (kDa)
n
R2
fapp (%)
M /p (kDa)
p
R2
initiator
time (min)
max conv
Đ
EBiB
PBiB
239
327
77
83
1.16 ± 0.01
1.46 ± 0.03
1.00 ± 0.03
0.931 ± 0.05
13.4 ± 0.4
10.8 ± 2.3
0.98
0.63
78 ± 4
96 ± 22
b
low Mp
16.7 ± 0.6
29.5 ± 1.0
27.7 ± 1.6
19.2 ± 0.9
0.98
0.98
0.96
0.97
high Mp
MBBiB
343
367
87
87
1.35 ± 0.04
1.24 ± 0.02
0.988 ± 0.02
1.10 ± 0.07
20.4 ± 0.6
13.9 ± 0.6
0.97
0.97
51 ± 8
75 ± 5
TMSPBiB
a
[
St]:[I]:[CuBr]:[CuBr ]:[PMDETA] = 100:1:1:0.1:1.1.; PMDETA = N,N,N′,N″,N″-pentamethyldiethylenetriamine; Đ = polydispersity = M /M
2
w
n
app
at the maximum conversion listed; kp = the apparent rate constants of propagation from the least-squares fits (slopes) of the data in Figure 1; M /
p are the slopes from the data in Figure 2, in which p = monomer conversion; R = the coefficient of determination for the statistical fits of the data in
Figures 2, 5 and 6; f = the apparent initiator efficiency from the data in Figure 2; M /p are the slopes from the data in Figures 5 and 6, in which M
is the peak molecular weight. This initiator efficiency is based on M for the entire bimodal molecular weight distribution.
n
2
app
p
p
b
n
mmol) in benzene-d (3.0 g) in a Schlenk tube was degassed by three
−d[M]
dt
6
•
R =
= k [P ][M]
p
p
freeze−pump−thaw cycles (5−10−5 min), and the Schlenk tube was
backfilled with nitrogen. After removing an aliquot (1.0 mL) with a
syringe, the remaining solution was added via a syringe to a mixture of
(1)
(2)
[M]0
[M]
•
app
ln
= k [P ]t = k
t
p
p
2
CuBr (44 mg, 0.31 mmol) and CuBr (7.1 mg, 32 μmol) under a N2
atmosphere. The reaction mixture was stirred at 25 °C, and aliquots
The polymerizations were also analyzed by GPC to determine the
(
1.0 mL) were removed with a syringe after 35 and 75 min. The
molecular weight data, initiator efficiency (f) and apparent initiator
aliquots were passed through a plug of basic activated alumina to
app
32
1
efficiency (f ) according to eqs 3 and 4, in which p is the extent of
remove the catalyst and were analyzed by H NMR spectroscopy.
theo
reaction, Mn
is the theoretical number-average molecular weight
Model Reaction of Propargyl Acetate with the ATRP
Catalyst System. A solution of propargyl acetate (35 mg, 36
based on the ratio of the amounts of monomer and initiator reacted,
and Mn is the observed Mn.
obs
μmol) and PMDETA (68 mg, 39 μmol) in benzene-d (3.83 g) was
6
degassed by three freeze−pump−thaw cycles (5−10−5 min) and then
[M]0
f[I]0
M = p
× MWmonomer
taken into the drybox. This solution was added to a mixture of CuBr
n
(3)
(4)
(
49 mg, 0.34 mmol) and CuBr (8 mg, 4 μmol) in a 20 mL vial, and
2
the mixture was stirred rapidly at room temperature for 30 min. An
aliquot (1.0 mL) of the mixture was transferred to each of four 20 mL
vials. The vials were capped and the screw caps were sealed to the vial
with electrical tape. The vials were removed from the drybox and three
vials were immersed in an oil bath at 85 °C. The reaction mixtures
were stirred at 85 °C and then removed from the oil bath at 1, 2.5, and
theo
f app = [[
P]
I]0
=
Mn
obs
Mn
RESULTS AND DISCUSSION
■
Kinetics of Styrene Polymerization. Table 1 summarizes
16.5 h, for comparison to the time 0 sample. These vials were cooled
the polymerization results for the ATRP polymerizations of
styrene at 110 °C using the control initiator and the three
alkyne-functionalized initiators shown in Scheme 2. This data
corresponds to the first-order monomer conversion plots
presented in Figure 1 and the plots of molecular weight vs
conversion presented in Figures 2, 5, and 6. All of the
polymerizations reached high conversions (77−87%) in 4−6 h,
and the semilogarithmic kinetic plots are linear throughout the
polymerizations. As summarized in Table 1, the apparent rate
to room temperature and exposed to the atmosphere to quench the
catalyst. The samples were filtered through a plug of basic activated
1
13
alumina and analyzed by H and C NMR spectroscopy.
Styrene Polymerizations: Kinetic Studies. The kinetic experi-
ments were performed in triplicate. In a typical procedure, a stock
solution of PMDETA (3.8 mL, 1.2 mmol; 0.27 g PMDETA/5.0 mL
anisole solution) was added by syringe to a solution of ethyl 2-
bromoisobutyrate (0.21 mg, 1.1 mmol) in styrene (11 g, 0.11 mol) in a
100 mL Schlenk tube equipped with a magnetic stir bar and sealed
app
−4 −1
with a rubber septum. This solution was degassed by three freeze−
pump−thaw cycles (5−15−5 min) and then taken into the drybox.
The contents of the Schlenk tube were added to a mixture of CuBr
constants (kp = (0.931−1.10) × 10 s ) using the alkyne
initiators are identical within experimental error to that of the
−4 −1
control initiator ((1.00 ± 0.03) × 10 s ). Therefore,
(
0.16 g, 1.1 mmol) and CuBr (26 mg, 0.12 mmol), and the resulting
2
functionalization of the ATRP initiator with a terminal alkyne
group or protected alkyne or propargylic groups does not result
in greater termination than that detected in the control
experiment with a nonalkyne initiator.
mixture was stirred rapidly at room temperature for 30 min. An aliquot
1.0 mL) of the polymerization mixture was transferred by syringe to
(
each of fifteen 20 mL vials. The vials were capped, and the screw caps
were sealed to the vial with electrical tape. The vials were removed
from the drybox and immersed in an oil bath at 110 °C. The
polymerization mixtures were stirred at 110 °C and then removed
from the oil bath in groups of three at five time intervals. These vials
were cooled in an ice bath to stop the reaction and exposed to
atmosphere to quench the catalyst.
Figure 2 plots the number-average molecular weights of the
polystyrenes produced as a function of monomer conversion
for the same ATRP polymerizations analyzed in Figure 1. The
data for the PBiB-initiated polymerization are quite scattered
2
(
R = 0.63) and nonlinear. As summarized in Table 1, the
1
molecular weight distributions are relatively broad (Đ = 1.31−
.46) at all conversions; the GPC chromatograms in Figure 3
demonstrate that these molecular weight distributions are
bimodal. When the two peak molecular weights (M ) of the
The polymerizations were analyzed by H NMR spectroscopy to
1
determine monomer concentration ([M]) and conversion at time t,
and the kinetic parameters (eqs 1 and 2), in which R is the rate of
p
•
polymerization, k is the rate constant of propagation, [P ] is the
p
p
app
concentration of growing chains, and kp
is the apparent rate
bimodal distributions are plotted as a function of monomer
conversion (Figure 4), both relationships are linear, which
constant of propagation.
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Figure 1. First-order monomer conversions in the atom transfer
radical polymerization of styrene (St) at 110 °C using the 2-
bromoisobutyrate initiators shown in Scheme 2 and N,N,N′,N″,N″-
pentamethyldiethylenetriamine (PMDETA) as the ligand; [St]:[I]:
Figure 3. Representative GPC chromatograms of polystyrene initiated
from prop-2-yn-1-yl 2-bromo-2-methylpropanoate (PBiB) at 110 °C at
64, 203, and 327 min using N,N,N′,N″,N″-pentamethyldiethylenetri-
amine (PMDETA) as the ligand; [St]:[PBiB]:[CuBr]:[CuBr
[PMDETA] = 100:1:1:0.1:1.1.
]:
2
[
CuBr]:[CuBr ]:[PMDETA] = 100:1:1:0.1:1.1; the error bars
2
correspond to one standard deviation from triplicate experiments.
Figure 4. Peak molecular weights (M ) of each distribution of the
p
Figure 2. Number-average molecular weight (M ) as a function of
bimodal molecular weight distributions produced by the atom transfer
radical polymerization of styrene (St) initiated by prop-2-yn-1-yl 2-
bromo-2-methylpropanoate (PBiB) at 110 °C as a function of
monomer conversion, using N,N,N′,N″,N″-pentamethyldiethylenetri-
n
monomer conversion for the atom transfer radical polymerizations of
styrene (St) at 110 °C using the 2-bromoisobutyrate initiators shown
in Scheme 2 and N,N,N′,N″,N″-pentamethyldiethylenetriamine
(
PMDETA) as the ligand; [St]:[I]:[CuBr]:[CuBr ]:[PMDETA] =
amine (PMDETA) as the ligand; [St]:[PBiB]:[CuBr]:[CuBr
[PMDETA] = 100:1:1:0.1:1.1.
]:
2
2
100:1:1:0.1:1.1. The theoretical molecular weight (dashed line) was
calculated as conversion × [M] /[I] × 104.15.
0
0
radical. We therefore synthesized MBBiB in which chain
transfer at the propargylic site is blocked by replacement of the
two propargylic hydrogen atoms with methyl groups. When
MBBiB was used to initiate the ATRP polymerization of
styrene, Mn evolved linearly with conversion (Figure 2),
confirming that chain transfer is absent. However, the
molecular weights are approximately twice the theoretical
values calculated from the initial ratio of the concentrations of
monomer to initiator. This corresponds to an apparent initiator
efficiency of 51 ± 8% (Table 1). Alternatively, the double
molecular weight may be due to a coupling reaction, rather than
inefficient initiation, as suggested by the results of the PBiB-
initiated polymerizations. In contrast to the PBiB-initiated
polymerizations, the molecular weight distributions are
monomodal and somewhat narrower (Đ = 1.37 at 86%
conversion vs Đ = 1.46 at 83% conversion).
demonstrates that chain transfer is not detectable. On average,
the peak molecular weights of the higher molecular weight
distributions are 1.8 times higher than those of the lower
molecular weight peaks (Table 1). The bimodal molecular
weight distributions and linear first-order kinetics are consistent
with a nondegenerative chain coupling reaction. However, the
higher molecular weight distributions can not be attributed to
termination by radical−radical coupling since the first-order
kinetic plots are linear and therefore do not detect termination
and because there is a bimodal molecular weight distribution at
all conversions, not just at the end of the polymerization. The
amount of coupled chains also varies from sample to sample
and with monomer conversion, creating the large scatter in the
M vs conversion plot in Figure 2.
n
One of the known sites for side reactions of alkynes under
radical polymerization conditions is at the propargylic position
The plot of the peak molecular weights for the MBBiB-
initiated polymerizations as a function of monomer conversion
in Figure 5 is linear, with a slope equal to that of the higher
(
Scheme 1D); chain transfer of a propargylic hydrogen atom is
favored by resonance stabilization of the resulting propargylic
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Figure 5. Peak molecular weights (M ) of the polymers produced by
Figure 7. Peak molecular weights (M
) of the polymers produced by
p
p
the atom transfer radical polymerization of styrene (St) initiated by
prop-2-yn-1-yl 2-bromo-2-methylpropanoate (PBiB; higher molecular
weight peak of bimodal distribution in black) and 2-methylbut-3-yn-2-
yl 2-bromo-2-methylpropanoate (MBBiB; monomodal distribution in
blue) at 110 °C as a function of monomer conversion, using
N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) as the
the atom transfer radical polymerization of styrene (St) initiated by
prop-2-yn-1-yl 2-bromo-2-methylpropanoate (PBiB; lower molecular
weight peak of bimodal distribution in black) and 3-(trimethylsilyl)-
prop-2-yn-1-yl 2-bromo-2-methylpropanoate (TMSPBiB; monomodal
distribution in green) at 110 °C as a function of monomer conversion,
using N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) as
ligand; [St]:[I]:[CuBr]:[CuBr ]:[PMDETA] = 100:1:1:0.1:1.1.
the ligand; [St]:[I]:[CuBr]:[CuBr ]:[PMDETA] = 100:1:1:0.1:1.1.
2
2
molecular weight distribution from PBiB (Table 1); this also
implies that a similar coupling side reaction occurs. Never-
theless, the higher molecular weights and monomodal
molecular weight distributions from MBBiB, as exemplified
by the GPC traces in Figure 6, suggest that the coupling
although not as narrow as the control polymerizations (Đ =
.18 at 77% conversion). A plot of the peak number-average
molecular weights as a function of conversion (Figure 7) is
linear, with a slope very close to that of the lower molecular
weight distribution from the PBiB-initiated polymerization
1
33
reaction is much more efficient with MBBiB than with PBiB.
(
Table 1). In contrast to MBBiB with the propargylic site
protected, TMSPBiB functions as well as EBiB, the nonalkyne
control initiator. Therefore, the dominant side reaction must be
alkyne−alkyne coupling, which is suppressed by protecting the
acetylenic position with a trimethylsilyl group. In order to
confirm this hypothesis, we analyzed the products formed by
PBiB and propargyl acetate under ATRP conditions in the
absence of monomer.
Model Reaction of PBiB. The possible transfer and
termination side reactions of the tertiary radicals generated by
1
PBiB were investigated by monitoring its H NMR spectra in
benzene-d in the presence of the catalyst system (CuBr, CuBr ,
6
2
and PMDETA) at room temperature and in the absence of
monomer. The concentrations and conditions were similar to
those used at the beginning of the polymerizations, when the
ligand is allowed time to complex the copper halides. As
outlined in Scheme 3, the tertiary radical generated by
homolytic cleavage of the activated carbon−bromine bond of
PBiB may abstract a propargylic hydrogen atom from a second
PBiB molecule, followed by quenching of the resulting
propargylic radical with cupric bromide to produce prop-2-
yn-1-bromo-1-yl 2-bromo-2-methylpropanoate and prop-2-yn-
Figure 6. Representative GPC chromatograms at 77−78% conversion
of polystyrene initiated from the 2-bromoisobutyrate initiators shown
in Scheme 2 at 110 °C using N,N,N′,N″,N″-pentamethyldiethylenetri-
amine (PMDETA) as the ligand; [St]:[PBiB]:[CuBr]:[CuBr ]:
2
[
PMDETA] = 100:1:1:0.1:1.1.
1
-yl 2-methylpropanoate. Although abstraction of a propargylic
The terminal alkyne position provides another potential site
hydrogen atom is favored by resonance stabilization of the
resulting propargylic radical, we saw no evidence of this
reaction in the PBiB-initiated polymerization of styrene.
Similarly, no chain transfer product formed by radical
abstraction of a propargylic hydrogen was detected in this
model reaction, even after 75 min.
for side reactions (Scheme 1). We therefore synthesized
TMSPBiB to block the terminal alkyne site by replacing the
hydrogen atom with a trimethylsilyl protecting group. When
the ATRP polymerization of styrene was initiated with
TMSPBiB (Figure 2), the molecular weight (M ) increased
n
linearly with conversion, and within experimental error, the
apparent initiator efficiency (75 ± 5%) was equivalent to that of
the control initiator (78 ± 4%) (Table 1). The molecular
weight distributions were monomodal and remained narrow (Đ
Alternatively, the tertiary radical may react with a second
isobutyrate radical by disproportionation to generate prop-2-
yn-1-yl methacrylate and prop-2-yn-1-yl isopropanoate, as in
the dominant termination mechanism of methacrylate polymer-
34
1
=
1.25 at 80% conversion) throughout the polymerization,
izations (Scheme 2). The H NMR spectrum in Figure 8
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DOI: 10.1021/acs.macromol.5b00652
Macromolecules 2015, 48, 3803−3810

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Article
Scheme 3. Chain Transfer vs Termination of the Tertiary Radicals Generated by Activation of Prop-2-yn-1-yl 2-Bromo-2-
methylpropanoate under Atom Transfer Radical Polymerization Conditions; PMDETA = N,N,N′,N″,N″-
Pentamethyldiethylenetriamine
1
Figure 8. H NMR (500 MHz) spectra of prop-2-yn-1-yl 2-bromo-2-methylpropanoate (PBiB) in benzene-d at 25 °C in the presence of CuBr,
6
CuBr and N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA); [PBiB]:[CuBr]:[CuBr ]:[PMDETA] = 1:1:0.1:1.1.
2
2
demonstrates that PBiB generated a substantial amount (24%)
of disproportionation products after 35 min under ATRP
conditions. This disproportionation side reaction may account
for the maximum initiator efficiency of the 2-bromoisobutyrate
initiators reported in Table 1, including the control initiator,
being only 78 ± 4%.
beginning of the polymerizations, although no monomer was
present, and the final reaction temperature was lower than that
of the polymerization due to the lower boiling point of benzene
compared to anisole/styrene. As in the polymerizations, the
model reactions were first stirred at room temperature to allow
the ligand to form complexes with copper prior to starting the
1
Model Reaction of Propargyl Acetate. The dominant
side reaction in the ATRP polymerizations initiated by PBiB
and MBBiB appears to be alkyne−alkyne coupling. Terminal
alkynes are rapidly dimerized by oxidative coupling using amine
reaction/polymerization. Figure 9 presents the H NMR
spectrum of the sample isolated after the initial 30 min at
room temperature. New singlet resonances appear at 1.47 ppm
and 4.23 ppm due to the formation of the alkyne−alkyne
coupled dimer, hexa-2,4-diyne-1,6-diyl diacetate, as confirmed
by 2-D gradient heteronuclear multiple bond correlation
(gHMBC) NMR spectroscopy (Figure S1 in the Supporting
Information).
The amount of this coupled side product (47% conversion
after 30 min at 25 °C) did not increase with additional reaction
time and heating. (Other side products were detected after 16.5
h at 85 °C but were not identified.) This demonstrates that the
oxidant was not present during the reaction, and the small
amount of Cu(II) present at equilibrium therefore does not
serve as the oxidant for the alkyne−alkyne coupling. Instead,
the oxidatively coupled dimer must form when oxygen is
present, either when the reactants are mixed together or at the
1
5−18
complexes of cuprous halides,
which are the most
common type of ATRP catalyst systems. These oxidative
coupling reactions also require the presence of oxygen or
another oxidant; although oxygen should be removed during
the extensive degassing procedure, Cu(II) is present in small
concentrations throughout the polymerization due to the
activation−deactivation equilibrium, and Cu(II) may therefore
act as the oxidant in an oxidative coupling reaction.
The possibility of alkyne−alkyne coupling was investigated
1
by monitoring the H NMR spectra of propargyl acetate in
benzene-d in the presence of the ATRP catalyst system (CuBr,
6
CuBr , and PMDETA), first at 25 °C and then at 85 °C. The
2
concentrations and conditions were similar to those used at the
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1
Figure 9. H NMR (500 MHz) spectra of propargyl acetate in benzene-d at 25 °C in the presence of CuBr, CuBr and N,N,N′,N″,N″-
6
2
pentamethyldiethylenetriamine (PMDETA); [propargyl acetate]:[CuBr]:[CuBr ]:[PMDETA] = 1:1:0.1:1.1.
2
end of the polymerization when the polymer is isolated. Since
the solution of propargyl acetate and PMDETA was thoroughly
degassed by a freeze−pump−thaw technique before adding it
to the mixture of CuBr and CuBr in a N -filled drybox, the
most likely time for coupling would have been at the end of the
reaction when the products were isolated in air.
AUTHOR INFORMATION
■
*
Corresponding Author
E-mail cpugh@uakron.edu; Tel (330) 972-6614 (C.P.).
2
2
Notes
The authors declare no competing financial interest.
CONCLUSIONS
ACKNOWLEDGMENTS
■
■
The ATRP polymerizations of 100 equiv of styrene initiated by
alkyne-functional initiators in the presence of a CuBr/CuBr2/
PMDETA catalyst system at 110 °C are living, with no
detectable termination reactions and no detectable chain
transfer reactions, including at the propargylic position,
according to first-order monomer conversion plots and
molecular weight plots as a function of monomer conversion,
respectively. Although the polymerizations initiated by
unprotected terminal alkyne-functional initiators are living,
the alkyne chain ends undergo oxidative alkyne−alkyne
coupling when the polymerizations are exposed to air, and
oxygen is introduced in the presence of CuBr/CuBr2/
PMDETA during work-up. This “side reaction” is of significant
importance, as it diminishes the orthogonality of CuCAAC/
ATRP and the control of ATRP polymerizations. Therefore, in
order to produce terminal alkyne-functionalized polymers with
controlled molecular weights and narrow polydispersities, the
alkyne group must be protected, such as with a trimethylsilyl-
protecting group as in the 3-(trimethylsilyl)prop-2-yn-1-yl 2-
bromo-2-methylpropanoate-initiated polymerizations.
Acknowledment is made to the National Science Foundation
for support of this research through DMR-1006195. We also
acknowledge Dr. Xiang Yan for synthesizing propargyl acetate.
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*
S
Supporting Information
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Synthesis of propargyl acetate and H− C gHMBC NMR
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Information is available free of charge on the ACS Publications
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