RAFT and click chemistry: A versatile approach to well-defined block copolymers

Article abstract of DOI:10.1039/b611224b

The combination of reversible chain transfer chemistry with highly orthogonal [2 + 3] cycloadditions ('click chemistry') allows for the synthesis of well-defined block copolymers of monomers with extremely disparate reactivities. The Royal Society of Chemistry.

Full text of DOI:10.1039/b611224b

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RAFT and click chemistry: A versatile approach to well-defined block
copolymers{
Damien Que´mener, Thomas P. Davis, Christopher Barner-Kowollik* and Martina H. Stenzel*
Received (in Cambridge, UK) 3rd August 2006, Accepted 25th September 2006
First published as an Advance Article on the web 12th October 2006
DOI: 10.1039/b611224b
steric hindrance of the polymer chains acts as a shield preventing
the molecular reaction between polymer end groups. However, the
coupling reaction was found to be achievable using ‘‘click
reactions’’4 such as copper-catalysed alkyne and azide 1,3-dipolar
cycloaddition (CuAAC) or the Diels Alder reactions (DA). The
term ‘‘click chemistry’’ was coined by Sharpless et al.5 to
encompass all reactions of high yields, modularity and stereo-
specificity. This method was first applied by van Hest et al.6 in
2005 for the synthesis of different block copolymers from PS,
PMMA and PEG homopolymers. PS and PMMA were both
prepared by ATRP. The ‘‘clickable’’ functions were subsequently
obtained by chemical reactions onto the chain end groups. In 2006,
Hizal et al.7 synthesized block copolymers from PS, PMMA, PEG
and PtBA using the same strategy. All polymers, except the PEG,
were prepared by ATRP and chain end groups were subsequently
modified to introduce an anthracene and a maleimide functions in
order to perform DA reactions.
The combination of reversible chain transfer chemistry with
highly orthogonal [2 + 3] cycloadditions (‘click chemistry’)
allows for the synthesis of well-defined block copolymers of
monomers with extremely disparate reactivities.
Block copolymers, in their diversities (selective solubilities, charge
repartition, molar mass balance, …), form part of essential
building blocks of ‘‘smart materials’’. Most of the new materials
with well-defined nano- and/or micro-structures1 can be employed
as powerful macromolecular engineering tools due to their
excellent ability to self-assemble.
Several routes can be considered to synthesize block copolymers.
The most convenient consists in the successive polymerization of
two or more monomers2 without purification steps of intermediate
compounds. However, this method is strongly limited to a few
monomers, usually with the same chemical and physical properties
(i.e. similar radical reactivity), which make them often inadequate
for the material synthesis by self-assembly. An alternative route is
Here we propose an alternative strategy by using mediating
agents (compounds 1 and 2, Scheme 1) carrying azide or acetylene
functions for the subsequent click reactions, avoiding the use of
any post-polymerization reactions. Moreover, polymerizations are
performed by reversible addition fragmentation chain transfer
(RAFT) instead of ATRP. RAFT polymerization8 is extremely
versatile as most of the vinylic monomers can be polymerized
under controlled/living conditions. For example, vinyl acetate is
easily polymerized with excellent control via RAFT using xanthate
(i.e. MADIX) agents, while the polymerization fails with ATRP.
However, RAFT agents must be chosen carefully according to the
monomer, which represents a severe limitation in block copolymer
synthesis. For example, vinyl acetate RAFT polymerization can
only be mediated by a xanthate agent,9 whereas styrene is
polymerized in the presence of dithiobenzoate compounds.10 The
only potential expectation to the above dilemma is the use of
universal RAFT agents such as F-RAFT, which hold great
the so-called macroinitiator method:3
a polymer chain is
chemically modified to be end-functionalized by an initiator
molecule in order to trigger the polymerization of the second
monomer. Although this method is applicable to a large variety of
monomers, the presence of residual homopolymers potentially
hidden by an increase of the molar mass distribution is difficult to
avoid, due to partial functionalization of the starting polymer and
an incomplete initiation of the second monomer’s polymerization.
Recently, a novel method has been successfully applied to block
copolymer synthesis, combining pericyclic [2 + 3] ‘‘click chemistry’’
and atom transfer radical polymerization (ATRP). Coupling of
two polymers is usually thermodynamically unfavorable. The
Centre for Advanced Macromolecular Design, The University of New
South Wales, Sydney, NSW 2052, Australia. E-mail: camd@unsw.edu.au
{ Electronic supplementary information (ESI) available: Synthetic proce-
dures and results of variable click reactions. See DOI: 10.1039/b611224b
Scheme 1 Synthesis of the ‘‘clickable’’ RAFT agents; see ESI{ for details on the synthetic procedure.
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Chem. Commun., 2006, 5051–5053 | 5051

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Scheme 3 Model CuAAC between PS homopolymers.
Table 1 Selected examples of ‘‘click’’ coupling of RAFT-made
homopolymers of PS and PVAc by CuAAC
Scheme 2 RAFT polymerization of vinyl acetate and styrene controlled
by the mediating agents 1 and 2.
Polymer-CMCH
Polymer-N3
Block copolymer
a
a
c
Mn,exp
/
Mn,exp
/
Mn,SEC
/
promise for sequential block copolymer formation of monomers
with disparate reactivities, such as styrene and vinyl acetate.11
Click chemistry can enable us to circumvent the problems posed
by conventional RAFT agents by synthesizing first a collection of
homopolymers by RAFT polymerization, and then by clicking
them together without further modification. In this contribution,
we illustrate this strategy via the synthesis of poly(styrene)-
b-poly(vinyl acetate). To the best of our knowledge, this work
represents the first example of the combination of RAFT
polymerization and highly orthogonal click chemistry to prepare
block copolymers. Furthermore, this is the first example of a
synthetic route to very narrow polydispersity poly(styrene)-
b-poly(vinyl acetate) copolymers.
kg mol21 PDIb
kg mol21 PDIb kg mol21 PDIb
1
2
3
4
5
a
PS 7.51
1.09 PS
1.12 PS
3.18
11.07
1.09 PVAc 6.83
1.12 PVAc 35.19
1.09 PVAc 3.71
1.11 10.60
1.13 19.41
1.16 15.24
1.18 45.26
1.17 12.15
1.14
1.14
1.18
1.24
1.17
PS 8.22
PS 7.51
PS 8.22
PS 7.51
Measured by gel permeation chromatography (GPC) in N,N-
dimethylacetamide (DMAC) with RI detector (calibration with PS
standards) and confirmed by NMR calculation. Measured by GPC
in DMAC with RI detector (calibration with PS standards).
Apparent molecular weight measured according to linear PS
standards.
b
c
mediating agents 1 and 2 (Scheme 2). Both mediating agents 1 and
2 effect a good control of the polymerization, up to relatively high
conversions. In both cases, the molecular weight increases linearly
with conversion (Fig. 1), leading to homopolymers with molecular
weight close to that expected and low PDI (polydispersity index).
Two RAFT agents were specifically designed to entail the func-
tionality required for the click chemistry. Xanthate derivative 1
(Scheme 1) was prepared in three steps by conventional substitu-
tion reactions, from the commercially available 3-bromo-1-
propanol. Dithiobenzoate derivative 2 (Scheme 1) was prepared
in one step using a carboxidiimide coupling reaction. A trimethyl
silyl group was used to protect the acetylene function, as the termi-
nal alkyne hydrogen may interfere with the radical polymerization.
RAFT polymerizations of vinyl acetate and styrene were
subsequently carried out in bulk at 60 uC in the presence of
Scheme 4 CuAAC between N3-PVAC (3) and MPS (4).
Fig. 1 Evolution of the number-average molecular weight with mono-
mer conversion. The dashed lines illustrate the theoretical number-average
molecular weight (calculated from GPC analyses).
Fig. 2 SEC curves of PSM, PVAC-N3, and its coupling product (entry 3,
Table 1).
5052 | Chem. Commun., 2006, 5051–5053
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and after the click reaction. The strong signal at 2100 cm21
assigned to the azide group disappeared completely in the
copolymer, proving the efficiency of the ‘‘click’’ reaction.
In conclusion, well-defined block copolymers PS-b-PVAc were
obtained by combining for the first time RAFT polymerization
and click chemistry. In a first part, new ‘‘clickable’’ RAFT agents
were designed and used to produce under control/living conditions
homopolymers of PS and PVAc. In a second part, ‘‘click’’
coupling reactions were performed, based on the conditions
determined via a model reaction. Experimental data (SEC, FT-IR)
demonstrate the formation of various block copolymers with
variable block ratios. In ongoing studies we intend to employ this
strategy for the preparation of more complex macromolecular
architectures such as star or dendrimer-like entities.
The authors are grateful for financial support from the
Australian Research Council (ARC) in the form of a Discovery
Grant (to M.H.S and C.B.-K). T.P.D. acknowledges an Australian
Professorial Fellowship (ARC). We also would like to acknowl-
edge Dr Tara Lovestead for her precious help with the mass
spectrometry, and the excellent management of the research center
(CAMD) by Dr Leonie Barner and Istvan Jacenjik.
Fig. 3 IR spectra of PSM, PVAC-N3 and its mixture before and after
‘‘click’’ coupling (entry 3, Table 1).
A model reaction of CuAAC was first carried out involving the
coupling of two PS homopolymers. In that way, the corresponding
block copolymer PS-b-PS is easily recovered (same solubility of the
two parts) and the true molecular weight is determined via SEC via
the use of a direct calibration with linear polystyrene standards. To
set up this experiment, an other dithiobenzoate RAFT agent
carying an azide group (6, Scheme 3) was prepared according to
the methodology described above. The same control of the
polymerization of styrene was observed, leading to homopolysty-
rene (5, Scheme 3) end-functionalized by an azide group. CuAACs
between N3-PS and M-PS were then performed. After surveying the
efficiency of reaction with a variety of CuI sources (CuBr, CuI,
CuSO4/sodium acsorbate,), ligands (DBU, PMEDTA, DIEA),
and solvents (DMF/H2O, THF), we found that the catalyst system
CuI/DBU/THF gives the best results with a reaction yield close to
completion. SEC analysis shows a clear molecular weight shift,
and the experimental molecular weight perfectly matches with the
expected one (Table 1, entry 1 and 2). Moreover, FT-IR
experiments show the complete disappearance at 2100 cm21 of
the azide signal.
Notes and references
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4 Selected recent articles about ‘‘click’’ reactions in polymer science:
V. Ladmiral, G. Mantovani, G. J. Clarkson, S. Cauet, J. L. Irwin and
D. M. Haddleton, J. Am. Chem. Soc., 2006, 128, 4823–4830;
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These conditions were kept for the subsequent CuAACs of
N3-PVAC (3) and M-PS (4) (Scheme 4). Various PS-b-PVAc block
copolymers of different molecular weights were prepared with
success (Table 1).
8 T. P. T. Le, G. Moad, E. Rizzardo and S. H. Thang, PCT Int. Appl.,
WO 9801478 A1 980115, 1998 (Chem. Abstr., 1998, 128, 115390);
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J. Polym. Sci., Part A: Polym. Chem., 2001, 39, 1353–1365.
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and C. Barner-Kowollik, Macromolecules, 2006, 39, 4584–4591;
A. Theis, M. H. Stenzel, T. P. Davis, M. L. Coote and C. Barner-
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Copolymers were all characterized by SEC in order to observe
the molecular weight distribution (Fig. 2). The comparison
between the starting homopolymers and the copolymer clearly
shows a molecular weight shift according to the ‘‘click’’ coupling.
However, a slight increase of the polydispersity index was detected
after the reaction, which could be due to the presence of remaining
homopolymers. This result can be explained by the difficulty to
work at the perfect stoichiometry 1 : 1 with polymers.12
Further confirmation of the ‘‘click’’ coupling can be taken from
FT-IR spectroscopy. In Fig. 3, the IR spectra of PS and PVAc
homopolymers are compared to the spectra of the mixture before
12 H. Gao and K. Matyjaszewski, Macromolecules, 2006, 39, 4960–4965.
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