Step-growth "click" coupling of telechelic polymers prepared by atom transfer radical polymerization

Article abstract of DOI:10.1021/ma050370d

The synthesis of homo- or heterotelechelic polymers and their efficient step-growth click coupling in the presence of CuBr, prepared by atom transfer radical polymerization (ATRP) was investigated. It was found that ATRP is an attractive technique for the synthesis of well-defined end-functionalized polymers. Homo- and heterotelechelic polySty oligomer prepared by the ATRP method were coupled via step-growth click coupling to yield polySty containing 1,2,3-triazole linkages. The SEC and H NMR spectroscopy results indicated the possibility of an intramolecular click reaction to yield cyclic polymers in DMF.

Full text of DOI:10.1021/ma050370d

3558
Macromolecules 2005, 38, 3558-3561
3
3
Step-Growth “Click” Coupling of Telechelic
Polymers Prepared by Atom Transfer Radical
Polymerization
reversible thiol oxidative coupling ) for the preparation
of high molecular weight polymeric materials.
Herein, we describe the synthesis of homo- or het-
erotelechelic polymers and their efficient step-growth
click coupling in the presence of CuBr. A one-pot ATRP-
nucleophilic substitution-click coupling process is re-
ported as well.
Nicolay V. Tsarevsky, Brent S. Sumerlin, and
Krzysztof Matyjaszewski*
Department of Chemistry, Carnegie Mellon University,
Experimental Section. An ATRP initiator contain-
ing an acetylene functionality was prepared by reacting
propargyl alcohol with 2-bromoisobutyric acid in the
presence of dicyclohexyl carbodiimide. The resulting
initiator, propargyl 2-bromoisobutyrate (PgBiB), was
used to prepare heterotelechelic polystyrene (polySty)
by ATRP ([Sty]:[PgBiB]:[CuBr]:[N,N,N′,N′′,N′′-penta-
methyldiethylenetriamine (PMDETA)] ) 40:1:1:1, 11 vol
% phenyl ether, 90 °C, 75 min). The resulting R-alkyne-
ω-bromo-terminated polystyrene (Mn ) 2590 g/mol, Mw/
Mn ) 1.12) was reacted with NaN3 in DMF to yield the
corresponding R-alkyne-ω-azido-terminated polystyrene.
This “monomer” was then click coupled in DMF at room
temperature in the presence of CuBr.
A one-pot ATRP-nucleophilic substitution-click cou-
pling process was achieved by (i) initiating Sty ATRP
with PgBiB ([Sty]:[PgBiB]:[CuBr]:[PMDETA] ) 76:1:
0.25:0.25, 44 vol % toluene, 80 °C, 200 min, Mn ) 960
g/mol, Mw/Mn ) 1.04), (ii) quenching the polymerization
by freezing with liquid nitrogen, (iii) adding NaN3,
ascorbic acid, and DMF, and (iv) equilibrating to room
temperature. The monomer conversion of the ATRP
reached 13% prior to addition of the subsequent re-
agents, and the click reaction was allowed to proceed
for 116 h.
4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213
Received February 21, 2005
Revised Manuscript Received March 25, 2005
Introduction. The methods of controlled/living radi-
1
cal polymerization (CRP) developed in the past decade
allow for the preparation of not only polymers with
predetermined molecular weight and narrow molecular
weight distribution but also a plethora of previously
unattainable polymeric materials. Numerous examples
2
3
of gradient and block copolymers have been reported
as well as polymers with complex architectures, includ-
4
5
6
ing polymer brushes, stars, and hyperbranched poly-
mers. The most widely used CRP methods are atom
7
-9
transfer radical polymerization (ATRP),
reversible
addition-fragmentation chain transfer (RAFT) polym-
1
0,11
12,13
erization,
nitroxide-mediated polymerization,
1
4
and degenerative transfer polymerization. Impor-
tantly, the polymers produced by ATRP contain termi-
nal halogen atom(s) and can be successfully derivatized
in various end group transformations, chiefly nucleo-
philic substitutions. The use of functional initiators
makes it possible to prepare either homo- or het-
1
5
erotelechelic polymers. Thus, ATRP is an attractive
technique for the synthesis of well-defined end-func-
tionalized polymers.
The nucleophilic substitution of a halogen atom from
a polymer chain end by an azide anion
R,ω-Dibromo-terminated polystyrene was prepared by
ATRP of Sty with a difunctional initiator ([Sty]:[di-
methyl 2,6-dibromoheptadioate (DM-2,6-DBHD)]:[CuBr]:
[PMDETA] ) 74:1:0.5:0.5, 40 vol % toluene, 80 °C, 140
min). The resulting polySty (M ) 1900 g/mol, M /M
1
6,17
is very
efficient and, when followed by reduction, leads to
amino-terminated polymers. Organic azides can be used
n
w
n
1
8,19
for a variety of chemical transformations.
dition reactions with alkynes, thoroughly studied by
Cycload-
) 1.09) was isolated, purified, and reacted with NaN
3
in DMF at room temperature to R,ω-diazido-terminated
polystyrene. After purification and isolation, this prod-
uct was reacted with propargyl ether in DMF at room
temperature with a CuBr catalyst.
20,21
Huisgen,
produce a mixture of substituted triazoles.
When the reaction is carried out in the presence of a
I
catalytic amount of Cu complexes, it yields 1,4-disub-
2
2,23
stituted triazoles exclusively.
This reaction along
Results and Discussion. The synthetic strategies
used to prepare high molecular weight polystyrene by
step-growth click coupling are presented in Scheme 1.
Mono- and dibromo-terminated polystyrene of low mo-
lecular weight were synthesized by ATRP using CuBr/
PMDETA as the catalyst and PgBiB or DM-2,6-DBHD
as the initiators, respectively. In the former case, the
polymer also contained an acetylene end group, which
could be used for further click coupling. The ATRP
reactions were stopped at relatively low monomer
conversion to ensure a high degree of bromine end-
with other 1,3-dipolar cycloadditions (such as the reac-
tion between azides and nitriles catalyzed by Lewis
acids) and other high-yield reactions are often termed
4
“
click reactions”.2 Click-type synthetic procedures are
attractive because of their near quantitative yields and
low susceptibility to side reactions. As such, they are
particularly important in preparative methods in which
high conversion of functional groups is desirable, e.g.,
in step-growth polymerization processes. Some click
reactions have already been successfully used in poly-
mer and materials chemistry. The efficient preparation
34,35
functionality.
The reactions of the polymers with
2
5
26
of well-defined polymeric tetrazoles, or dendrimers,
sodium azide yielded the corresponding azido-terminat-
2
7
amphiphilic block copolymers, cross-linked block co-
1
ed polymers. Based on H NMR spectroscopy, the
2
8
29
polymer vesicles, and adhesives with triazole units
has been reported. Click reactions were also used in the
nucleophilic substitution was complete within several
hours (Figure 1).
30
synthesis of functionalized poly(oxynorbornenes) and
The R-alkyne-ω-azido-terminated polystyrene “mono-
mer” was then self-coupled in the presence of CuBr in
DMF at room temperature. Since CuBr exhibits suf-
ficient solubility in DMF, addition of no extra ligand was
necessary to achieve efficient coupling. The only precau-
tion taken was that the reaction was performed under
3
1
block copolymers and are a convenient alternative to
other coupling reactions applied to polymers prepared
by ATRP (such as atom transfer radical coupling32 or
*
Corresponding author. E-mail: km3b@andrew.cmu.edu.
1
0.1021/ma050370d CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/07/2005

Macromolecules, Vol. 38, No. 9, 2005
Communications to the Editor 3559
Scheme 1. Click Coupling Reactions Using Telechelic Polymers Prepared by ATRP: (a) Synthesis of
r-Acetylene-ω-azido-Terminated Polystyrene and Its Subsequent Homocoupling and (b) Synthesis of
a
Diazido-Terminated Polystyrene and Its Coupling with Propargyl Ether
a
Reaction conditions: (i) NaN
3
in DMF, room temperature, 4 h; (ii) CuBr in deoxygenated DMF, room temperature; and (iii)
propargyl ether and CuBr in deoxygenated DMF, room temperature.
molecular weight polymer in the mixture increased, not
all of the starting material appeared to be consumed.
The elution volume of the low molecular weight fraction
in the product was slightly higher than the starting
material, possibly indicating that cyclization occurred.
The hydrodynamic volume of the cyclic product obtained
by intramolecular self-coupling should be lower than the
parent polymer, and thus a lower apparent SEC mo-
lecular weight is expected. The high extent of cyclization
may be a result of DMF being a rather poor solvent for
polySty,36 since the propensity for intramolecular reac-
tion is increased for a compact coil. The remaining low
molecular weight material present at even long reaction
times (Table 1a) served as further evidence of cycliza-
tion. After 14.5 h, the low molecular weight peak
constituted 18% of the total area of the SEC trace and
essentially remained constant even after 89 h of reaction
time. Meanwhile, the coupling products continuously
increased in molecular weight, indicating that the
conditions were still appropriate for the reaction to take
place and the activity of the CuBr catalyst was pre-
served. The reaction was stopped at this point, and the
1
polymer was analyzed by H NMR spectroscopy (Figure
1
a). The fraction of residual azido groups in the product
was very small, indicating essentially complete “mono-
mer” consumption to either high molecular weight
polymer or cyclic product. As evidenced by SEC, a small
portion of double molecular weight chains was present
in the starting material due to radical-radical termina-
tion during ATRP. These chains contain two alkyne end
groups and potentially limit the degree of polymeriza-
tion of the click coupled chains. The alkyne at the chain
end may also copolymerize during ATRP, and such a
branched product can additionally broaden the molec-
ular weight distribution of the final polymer.
This study also considers the possibility of conducting
the ATRP of Sty with an alkyne-containing initiator,
end-group substitution with NaN3, and subsequent click
coupling of the resulting heterotelechelic polymers as a
one-pot procedure. For this purpose, the ATRP reaction
mixture of Sty initiated with PgBiB was cooled in liquid
nitrogen, and a mixture of sodium azide and ascorbic
1
Figure 1. H NMR spectra of (a) R,ω-heterotelechelic poly-
styrene and its click coupled product and (b) R,ω-homotelech-
elic polystyrene and the corresponding product after click
coupling with propargyl ether.
a nitrogen atmosphere in order to avoid air oxidation
I
II
of the Cu compound. Figure 2a shows the evolution of
acid (to reduce the Cu complexes formed during the
the SEC traces with time.
polymerization) was added under a nitrogen atmo-
sphere. The one-pot procedure was less efficient than
the click coupling reaction of the isolated materials, as
judged by SEC analysis (Figure 2b). Because only a
limited amount of high molecular weight product was
obtained during the coupling process, we were not able
to determine an accurate molecular weight for the
As seen in Table 1, the click coupling of the parent
R-alkyne-ω-azido-terminated polystyrene (Mn ) 2590
g/mol, Mw/Mn ) 1.11) resulted in a polymer of high
molecular weight (Mn ) 21 500 g/mol) and broad mo-
lecular weight distribution (Mw/Mn ) 4.85), as expected
for a step-growth process. While the amount of high

3560 Communications to the Editor
Macromolecules, Vol. 38, No. 9, 2005
Figure 2. Evolution of the SEC traces during step-growth click coupling of (a) R-alkyne-ω-azido-terminated polySty after its
isolation and mixing with CuBr in DMF, (b) the similar reaction performed in one-pot, and (c) a mixture of diazido-terminated
polySty with propargyl ether.
Table 1. SEC Data from the Click Coupling of Hetero-
and Homotelechelic PolySty
providing evidence that a cyclic product was most likely
formed during the reaction.
LMW fractionc
Conclusions. Homo- and heterotelechelic polySty
oligomers prepared by ATRP were coupled via step-
growth click coupling to yield polySty containing 1,2,3-
triazole linkages. R-Alkyne-ω-azido-terminated polySty
was click coupled at room temperature in DMF with a
CuBr catalyst. As a result of the click reaction being
conducted in DMF, no additional ligand was necessary
to solubilize the CuBr catalyst. Additionally, because
both ATRP and azide-alkyne click reactions are cata-
HMW productd
coupling time peak area
e
Mn,appf Mw/Mnf
Mnf
Mw/Mnf
reaction
(h)
(%)
a
0
100
18
18
17
100
7
2590
1920
1900
1920
2020
1570
1540
1550
1.11
1.04
1.04
1.04
1.09
1.03
1.03
1.03
1
4.5
1.5
9
15 500
15 600
21 500
2.43
2.35
4.85
2
8
b
0
1
2
4
6.5
13 700
14 800
16 700
2.77
3.15
3.34
4
7
I
lyzed by Cu compounds, a one-pot ATRP-nucleophilic
0
7
substitution-click coupling process was attempted. So
far, this approach has led to only moderate success.
Another method involved R,ω-diazido-terminated poly-
Sty being polymerized with propargyl ether at room
temperature to yield higher molecular weight polySty.
In all cases, the resulting click coupled polySty was
polydisperse with moderate to high molecular weight.
a
Click coupling of R-alkyne-ω-azido-terminated polySty. b Click
coupling of R,ω-diazido-terminated polySty with propargyl ether.
c
Low molecular weight fraction of the SEC trace after Gaussian
peak fitting. d Click coupled polymersremaining portion of the
e
SEC trace excluding the low molecular weight fraction. Percent
of the total SEC trace area. f Number-average molecular weight
and polydispersity of each molecular weight fraction as determined
by SEC (polySty calibration).
1
SEC and H NMR spectroscopy indicated the pos-
sibility of an intramolecular click reaction to yield cyclic
polymers in DMF. This phenomenon is currently under
further investigation and will be the subject of a future
publication.
coupled products. The decreased rate of reaction in the
one-pot process may be a result of competing side
reactions between the inorganic azide and the acetylene
groups, which would result in N-unsubstituted triazoles
and prevent further step growth.37
Acknowledgment. The authors thank the members
of the CRP Consortium at Carnegie Mellon University
(CMU) and NSF (Grant DMR 0090409) for funding.
N.V.T. gratefully acknowledges support from the Har-
rison Legacy Dissertation Fellowship (CMU).
Finally, a click reaction was performed using a 1:1
mixture of diazido-terminated polystyrene and propar-
gyl ether (Table 1b). After the addition of the acetylene
derivative to the solution of polymer and CuBr in DMF,
the reaction mixture became bright yellow and turbid
I
due to formation of a Cu -alkyne complex. After 20-
Supporting Information Available: Procedures for the
preparation of propargyl 2-bromoisobutyrate and homo- and
heterotelechelic polystyrenes and their step-growth click cou-
pling. This material is available free of charge via the Internet
at http://pubs.acs.org.
3
0 h, there was a noticeable increase in solution
viscosity. The molecular weight and polydispersity of
the polymer (Figure 2c) increased with time, as in the
other step-growth-type polymerization processes dis-
cussed above. A polymer with an Mn of 16 700 g/mol and
Mw/Mn ) 3.34 was obtained by click coupling of the R,ω-
diazido-terminated polySty with an original Mn of 2020
g/mol and Mw/Mn of 1.09. As in the case of coupling of
the heterotelechelic polySty in DMF, a small and
constant amount (7%) of polymer of lower apparent
molecular weight than the starting material remained
in the mixture, most likely a product of cyclization. The
portion of polySty that reacted with propargyl ether to
form cyclic chains is rendered unreactive; therefore, its
concentration as determined by SEC does not appear
to change with time, despite the step-growth process
continuing to higher molecular weight. No unreacted
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MA050370D