Controlled radical polymerization of active ester monomers: Precursor polymers for highly functionalized materials

Article abstract of DOI:10.1021/ma035876f

Controlled radical polymerization of active ester monomers was discussed. The study was carried out by using atom transfer radical polymerization (ATRP). The atom transfer radical polymerization offered the possibility to prepare block polymers. It was fo

Full text of DOI:10.1021/ma035876f

Volume 37, Number 15
J uly 27, 2004
© Copyright 2004 by the American Chemical Society
Communications to the Editor
acrylates.7-9 Precursor polymers based on NHS-(meth)-
Con tr olled Ra d ica l P olym er iza tion of Active
Ester Mon om er s: P r ecu r sor P olym er s for
High ly F u n ction a lized Ma ter ia ls
acrylates offer the possibility to obtain multifunctional
polyacrylamides simply by a polymer analogous reac-
tion.8 However, poly(N-hydroxysuccinimide (meth)acry-
lates) (pNHS) suffer from the fact of their poor solubility;
i.e., polymer analogous reactions can only be performed
in DMF or DMSO solution.10 Hence, there is still a great
interest in novel active ester polymers.
P a tr ick Th ea to,*,† J on g-Uk Kim ,† a n d
J on g-Ch a n Lee‡
Institut fu¨r organische Chemie, Universita¨t Mainz,
Duesbergweg 10-14, D-55099 Mainz, Germany, and
School of Chemical Engineering, Seoul National University,
Seoul 151-744, Korea
Nevertheless, NHS-methacrylates have been polym-
erized under controlled radical conditions.11,12 ATRP
showed good results regarding the control of molecular
weight and polydispersities. However, the initiator
efficiency in these systems was typically below 50%.11
Attempts to polymerize NHS-methacrylate by RAFT
have not been satisfactory.12 In comparison, 2-vinyl-4,4-
dimethyl-5-oxazolone had been polymerized by RAFT
with control of molecular weight and polydispersities
around 1.1.12
Received December 11, 2003
Revised Manuscript Received May 15, 2004
Recently, atom transfer radical polymerization (ATRP)
has gained a lot of attention as a versatile polymeriza-
tion technique.1-3 It is one of the most successful
methods to polymerize a variety of monomers under
controlled conditions. The control in this polymerization
process results from the fast exchange reaction between
propagating radicals and dormant species. Thereby the
concentration of propagating radicals is kept sufficiently
low, suppressing termination and transfer reactions.
The resulting polymers are well-defined with a good
control over molecular weight, and low polydispersities
(PDI < 1.3) can be obtained. Successful preparation of
various functional polymers and block copolymers, as
described in the literature, proved the potential of
ATRP.
Active esters proved exceedingly useful in synthetic
peptide chemistry.4 Aminolysis of active esters proceeds
by nucleophilic displacement at the carbonyl group, i.e.,
by acyl-oxygen fission. Various active ester polymers
have been described by Ringsdorf et al.,5,6 but most of
them did not find broad scientific application. Mainly
active esters based on N-hydroxysuccinimide (NHS) are
in use in polymer science in the form of NHS-(meth)-
To the best of our knowledge, other active ester
monomers have not been investigated by any controlled
radical polymerization method. To develop novel poly-
mer structures with their application in biopolymer
science, we examined within this study the controlled
radical polymerization by ATRP of two different active
ester acrylates: 2,4,5-trichlorophenol acrylate (1)13 and
endo-N-hydroxy-5-norbornene-2,3-dicarboxyimide acry-
late (2),14 as shown in Scheme 1. All polymerizations
were conducted under similar conditions. 2-Bromoisobu-
tyric ethyl ester, CuBr, and 2,2′-biypyridine (bipy)
initiated each monomer at 90 °C.15 Monomer 2 was
polymerized in DMSO solution, similar to the descrip-
tion of NHS-methacrylate by Mu¨ller et al.11 Monomer
1 was polymerized in bulk, resulting in a better control
than in DMSO. The polymers were isolated by precipi-
tation into 2-propanol. While p(NHS) is only soluble in
DMSO or DMF, the polymers P 1 and P 2 show a better
solubility and can be dissolved in most common organic
solvents, such as CHCl3, THF, etc. In other words, P 1
and P 2 are already superior to p(NHS) considering any
following polymer analogous reaction.
† Universita¨t Mainz.
‡ Seoul National University.
* Corresponding author: phone +49-(0)6131-3926256; Fax +49-
(0)6131-3924778; e-mail theato@uni-mainz.de.
10.1021/ma035876f CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/02/2004

5476 Communications to the Editor
Macromolecules, Vol. 37, No. 15, 2004
F igu r e 1. (a) Kinetics for the ATRP of 1 in bulk at 100 °C. (b) Mn and Mw/Mn vs conversation for ATRP of 1. (c) Kinetics for the
ATRP of 2 in DMSO at 90 °C. (d) Mn and Mw/Mn vs conversation for ATRP of 2.
Sch em e 1
The first-order plots of the respective polymerizations
of 1 and 2 are shown in Figure 1. The polymerization
of NHS-methacrylate proceeds rapidly; as reported, the
polymerization is complete after 15 min.11 Probably due
to the reactive character of NHS-methacrylate a perfect
control could not be achieved, as indicated by the low
initiator efficiency, even though low polydispersities
could be obtained.
Searching for less reactive monomers with even a
better control during the polymerization, we investi-
gated monomer 2, which is a sterically hindered NHS-
acrylate. Because of the bulkiness of the norbonene
group, we expected a lower polymerization rate and
therefore a better control. Figure 1c shows the first-
order plot of 2. A linear behavior could be observed for
up to 40 h. In the same time the evolution of molecular
weight increased linearly with conversion, while the
polydispersity leveled off at 1.1-1.2. As the straight line
for the theoretical molecular weight showed, the initia-
tor efficiency was satisfactory. Quantitative efficiencies
could be realized within the error range. Comparing the
polymerizations of 1 and 2 under ATRP conditions, only
2 showed a satisfactory controlled radical polymeriza-
tion. Nevertheless, 1 could be polymerized under ATRP
conditions, even though the control is not accurate.
In comparison, the polymerization of 1 proceeded
slower, and we hoped with better control. Within the
first 30 min the first-order plot was linear (Figure 1a).
Afterward, a deviation from the linear variation of
conversion with time in semilogarithmic coordinates
occurred, indicating that the constant concentration of
active species in the polymerization decreased. Then the
kinetic of the polymerization seemed to show a linear
behavior again. The evolution of the molecular weight
(Figure 1b) seemed to follow a linear progress, and the
initiator efficiency was between 50% and 70%. This can
be seen by the straight line representing the theoretical
molecular weight which was consistently smaller than
the actual molecular weight. Even though the initiator
efficiency was better than for the polymerization of
NHS-methacrylates (12%-61%), it is not completely
satisfying yet. Nevertheless, narrow molecular weight
distributions (Mw/Mn ) 1.2-1.3) of P 1 could be obtained.
As the conversion and the molecular weight of the
polymer were kept low despite the repetitive polymer-
ization using bipy as a ligand, other ligands, such as
1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetrade-
cane (4N) and 1,1,4,7,7-pentamethyldiethyleneamine
(3N), which are known to increase the rate of the
polymerization, were investigated. The polymerizations
of 1 and 2 using the ligands 3N or 4N were performed
under the same conditions as in the case of bipy.

Macromolecules, Vol. 37, No. 15, 2004
Communications to the Editor 5477
Ta ble 1. Con d ition s a n d Resu lts for th e ATRP of
Mon om er 2 Va r yin g th e In itia tor Ra tioa
b
[M]0/[I]0
time [h]
conv [%]
Mn
PDI
Mn(theo)c
150
100
50
19.5
18
18.5
24
13.0
14.0
21.7
35.0
4360
3420
2550
2260
1.34
1.27
1.34
1.14
4547
3264
2530
2285
28
a
Reaction conditions: 90 °C, DMSO, [bipy]:[CuBr]:[I] ) 2:1:1.
b
The molecular weights were calculated by end-group analysis
by 1H NMR. c [M]0/[I]0 × conversion × 233.2 g/mol.
However, despite higher conversions of the polymeri-
zation with 3N or 4N, a narrow polydispersity was not
achieved. For example, in the case of polymerization of
monomer 1 with 3N at room temperature, a bimodal
GPC curve was obtained (PDI ∼ 2), while the conversion
was very high (>95%). Therefore, 3N and 4N ligands
seemed not to be adequate for the controlled polymer-
ization of monomers 1 and 2.
F igu r e 2. SEC traces of block copolymer P 2-b-PMMA (dotted
line) and macroinitiator P 2-Br (solid line) obtained by ATRP.
water phase. This could be observed as the emulsion
broke down forming the two clear phases. The released
endo-N-hydroxy-5-norbornene-2,3-dicarboxyimide re-
mained in the chloroform phase. Thus, the separation
of the resulting polymer was very convenient, and the
endo-N-hydroxy-5-norbornene-2,3-dicarboxyimide could
be reused since it is the only compound in the chloroform
phase, which offers an environment-friendly reaction
cycle.
Table 1 summarizes the monomer to initiator depen-
dence for constant reaction conditions of the polymeri-
zation of 2 (∼20 h, 90 °C). As expected with increasing
monomer concentration higher molecular weights could
be obtained. The polymerization of 2 occurred slower
compared to NHS-methacrylate or monomer 1. After
20 h of polymerization time conversions up to 20% were
obtained, except for the very low monomer-to-initiator
ratio of 28. Thus, experiments to increase the conversion
were made. As reported for the polymerization of NHS-
methacrylate, the concentration of DMSO influenced the
polymerization. Varying the solvent-to-monomer ratio,
similar effects were found. The conversion of polymer-
izations performed under constant reaction conditions
(90 °C, 19 h) varied dramatically with the solvent-to-
monomer ratio. At least a monomer concentration
higher than 25 wt % was needed for the polymerization
of monomer 2. There appears to be a threshold concen-
tration (25-50 wt %) for successful polymerization. At
concentrations higher than 70 wt % the conversion
decreased again. Thus, it is quite certain that the
polymerization rate increased as the concentration
increased, however only up to a certain value. Evidently,
increasing the temperature increased the polymeriza-
tion rate likewise. Even though the overall conversions
are not very high, reasonable molecular weights can be
obtained. Further studies to increase the conversion are
in progress.
The outstanding advantage of the active ester poly-
mers P 1 and especially P 2 is the possibility to transform
them to polyacrylamides simply by a polymer analogous
reaction.17 As the polymers P 1 and P 2 are soluble in
organic solvents, e.g., chloroform, the preparation of
water-soluble functionalized polyacrylamides may be
carried out under phase-transfer conditions. The pre-
cursor polymer P 2 was dissolved in the chloroform
phase, and an amine (as an example ammonia) was
dissolved in the upper water phase. Both phases were
clear before mixing. After the phases were stirred the
mixture turned turbid and then within 5 min milky.
After an additional 10 min the solution turned clear
again. During the vigorous stirring of the phases, the
precursor polymer P 2 partly reacted with ammonia
forming an intermediated amphiphilic polymer that
emulsified the solution. The amphiphilic character could
be assigned to the existence of units of acrylamide and
2 in the polymer. As the reaction proceeded this
intermediate amphiphilic polymer converted completely
to polyacrylamide, which only dissolved in the upper
Block copolymers of monomer 2 and MMA were
prepared. Monomer 2 was first polymerized under the
established optimum conditions. After precipitation and
purification the homopolymer was used as a macroini-
tiator to initiate the polymerization of MMA in DMSO.
After 2 h of polymerization the block copolymer was
precipitated into 2-propanol.16 Figure 2 plots the GPC
curves of the homopolymer P 2 and the resulting block
copolymer P 2-b-PMMA (solid line and dotted line,
respectively). P 2 had a molecular weight of Mn ) 3550
with a polydispersity of 1.33. The block copolymer had
a molecular weight of Mn ) 13 950 with a polydispersity
of 1.7. Clearly, the polymerization conditions seemed not
to be optimal and will be tuned in ongoing experiments.
Nevertheless, the initiation of P 2 was quantitative, as
no low molecular weight homopolymer P 2 could be
detected after polymerization of MMA (dotted line in
1
Figure 2). H NMR analysis showed signals for MMA
and monomer 2 units, thus supporting the obtained
block copolymer structure.16 This may lead to a variety
of novel functionalized block copolymers as the active
ester group can be transformed to polyacrylamides by
simple polymer analogous reactions. Reaction of the
block copolymer P 2-b-PMMA with ammonia in THF
solution at room temperature led to the block copolymer
PAAM-b-PMMA,17 showing that the ester group of
PMMA was not reacting through a competitive nucleo-
philic attack. Further studies to quantify the polymer
analogous reactions are in progress and will be pub-
lished elsewhere.
In summary, two reactive ester monomers 1 and 2
were polymerized by ATRP. Monomer 2 was polymer-
ized with 100% initiator efficiency. Additionally, polym-
erization kinetics proved the controlled polymerization
behavior. Further this method offered the possibility to
prepare block copolymers. These resulting precursor
polymers could successfully react with amines in a
polymer analogous reaction under homogeneous or
heterogeneous conditions. Thus, this strategy offers not
only the possibility to prepare highly functionalized
homopolymers but also highly functionalized block
copolymers.

5478 Communications to the Editor
Macromolecules, Vol. 37, No. 15, 2004
MHz, CDCl3, δ, ppm): 6.63 (d, 1H, vinyl H), 6.19 (m, 4H,
vinyl H), 3.44 (s, 2H), 3.32 (s, 2H), 1.78 (d, 1H), 1.53 (dd,
1H).
Ack n ow led gm en t. J .-U. Kim gratefully acknowl-
edges the DAAD and KOSEF for granting a summer
scholarship. The University of Mainz is acknowledged
for financial support.
(15) All polymerizations were performed under ATRP (atom
transfer radical polymerization) conditions. Generally, in a
polymerization of endo-N-hydroxy-5-norbornene-2,3-dicar-
boxyimide acrylate (2), copper(I) bromide (45 mg, 0.27
mmol), 2,2′-bipyridine (104 mg, 0.54 mmol), and monomer
2 (1.68 g, 7.5 mmol) were added to a flask, which was then
sealed with a septum followed by drying in a vacuum for
30 min. After the flask was purged with nitrogen, distilled
DMSO (0.3 mL) was then injected into the flask at 90 °C.
The resulting mixture was magnetically stirred until the
solution became homogeneous. A degassed solution of 2-bro-
moisobutyric ethyl ester (54 mg, 0.27 mmol) in DMSO (0.2
mL) was then injected into the mixture. The conversion of
the polymerization and the number-average molecular
weight (Mn) were calculated from 1H NMR of a sampled
portion of the mixture by comparing of the integrals of the
peaks corresponding to monomer, polymer, and initiator.
Purification of the polymer was performed by precipitation
the solution into 2-propanol. Monomer 1 was polymerized
at 100 °C without solvent. Gel permeation chromatography
(GPC) measurements were performed with a house-made
GPC equipped with a PU-980 pump, a RI-930 detector, and
a J asco UV dectector using columns from PSS. THF was
used as an eluent with a flow rate of 1.0 mL/min.
(16) The P 2-b-PMMA diblock copolymer was synthesized using
P 2 homopolymer as a macroinitiator. To the vial containing
P 2 (30 mg, 0.01 mmol), CuBr (19 mg, 0.14 mmol), and bipy
(42 mg, 0.28 mmol) in 0.3 mL of DMSO, 0.7 mL (6.6 mmol)
of MMA was injected at 70 °C. After 2 h the solution was
precipitated into cold 2-propanol to afford a white solid. P 2-
b-PMMA: 1H NMR (300 MHz, CDCl3, δ, ppm): 6.15, 3.57,
3.37, 3.27, 1.84, 1.42, 1.18, 0.99, 0.82.
(17) The polymer analogous reaction of P 2 and P 2-b-PMMA
under homogeneous conditions was performed as follows:
to the vials containing the polymer in 5 mL of dried
tetrahydrofuran, 1 equiv of ammonia was added. The mix-
tures were allowed to react at room temperature. After
ammonia and THF were evaporated, the crude product was
dissolved in THF and purified by precipitation into cold
diethyl ether.
Su p p or tin g In for m a tion Ava ila ble: Experimental sec-
tion. This material is available free of charge via the Internet
at http://pubs.acs.org.
Refer en ces a n d Notes
(1) Matyjaszewski, K.; Xia, J . Chem. Rev. 2001, 101, 2921.
(2) Patten, T. E.; Matyjaszewski, K. Acc. Chem. Res. 1999, 32,
895.
(3) Patten, T. E.; Matyjaszewski, K. Adv. Mater. 1998, 10, 901.
(4) Bodanszkym, M. Principles of Peptide Chemistry;
Springer: Berlin, 1984; Vol. 16.
(5) Batz, H. G.; Franzmann, G.; Ringsdorf, H. Makromol. Chem.
1973, 172, 27.
(6) Batz, H. G.; Franzmann, G.; Ringsdorf, H. Angew. Chem.
1972, 84, 1189.
(7) Hermanson, G. Bioconjugate Techniques; Academic Press:
New York, 1996; p 139.
(8) Theato, P.; Zentel, R. Langmuir 2000, 16, 1801.
(9) Theato, P.; Zentel, R.; Schwarz, S. Macromol. Biosci. 2002,
2, 387.
(10) Ferruti, P.; Bettelli, A.; Fere, A. Polymer 1972, 13, 463.
(11) Godwin, A.; Hartenstein, M.; Mu¨ller, A. H. E.; Brocchini,
S. Angew. Chem. 2001, 113, 614.
(12) Schilli, C. M.; Mu¨ller, A. H. E.; Rizzardo, E.; Thang, S. H.;
Chong, Y. K. ACS Symp. Ser. 2003, 854, 603.
(13) Monomer
1 was synthesized by the reaction of 2,4,5-
trichlorophenol with acryloyl chloride (1 equiv) in dried THF
in the presence of triethylamine (1 equiv). The crude product
was purified by recrystallization from ethanol. Yield: 67%;
mp: 64.3 °C. 1H NMR (300 MHz, CDCl3, δ, ppm): 7.55 (s,
1H, arom H), 7.32 (s, 1H, arom H), 6.65 (d, 1 H, vinyl H),
6.31 (dd, 1H, vinyl H), 6.09 (d, 1H, vinyl H).
(14) Monomer 2 was synthesized by the reaction of endo-N-
hydroxy-5-norbornene-2,3-dicarboxyimide with acryloyl chlo-
ride (1 equiv) in dried THF in the presence of triethylamine
(1 equiv). The crude product was purified by recrystalliza-
tion from ethanol. Yield: 84%, mp: 114.4 °C. 1H NMR (300
MA035876F