Multihydroxyl-functional polystyrenes in continuous flow

Article abstract of DOI:10.1021/ma902849r

We describe the synthesisof end-functionalized polystyrenes byliving anionic polymerization ina microstructured reactor via termination by acetal-protected functional epoxides. Initiation of styrene polymerization by alkyllithium takes place in a micromix

Full text of DOI:10.1021/ma902849r

5582 Macromolecules 2010, 43, 5582–5588
DOI: 10.1021/ma902849r
Multihydroxyl-Functional Polystyrenes in Continuous Flow
Christoph Tonhauser,† Daniel Wilms,† Frederik Wurm,† Elena Berger-Nicoletti,†
†
,†
Michael Maskos,‡,§ Holger Lowe, and Holger Frey*
€
†Institute of Organic Chemistry, Organic and Macromolecular Chemistry, Duesbergweg 10-14 Johannes
Gutenberg-University Mainz, 55099 Mainz, Germany, ‡Institute of Physical Chemistry,
§
Johannes Gutenberg-University Mainz, 55099 Mainz, Germany, and Federal Institute for Material Research
and Testing BAM, Unter den Eichen 87, 12205 Berlin, Germany
Received December 28, 2009; Revised Manuscript Received March 28, 2010
ABSTRACT: We describe the synthesis of end-functionalized polystyrenes by living anionic polymerization in a
microstructured reactor via termination by acetal-protected functional epoxides. Initiation of styrene polymeri-
zation by alkyllithium takes place in a micromixing device with efficient heat and mass transfer properties. A newly
developed continuous polymerization-termination sequence enabled quantitative functionalization of the living
carbanions by nucleophilic displacement with different, specifically designed glycidyl ethers (ethoxy ethyl glycidyl
ether (EEGE), 1,2-isopropylidene glyceryl glycidyl ether (IGG), and trans-2-phenyl-1,3-dioxane glycidyl ether
(PDGE)). Upon acidic hydrolysis the end-capped polystyrenes release multiple hydroxyl groups (2-3) at the chain
end. Temperature and flow rates have been varied to control molecular weights and to optimize the reaction
conditions for maximum polymerization and termination efficiency. The polymers were analyzed in detail using
NMR spectroscopy, size exclusion chromatography (SEC), and MALDI-ToF-MS. Molecular weights of the
samples prepared ranged between 1800 and 9000 g/mol. For all of the novel termination agents full termination was
confirmed by MALDI-ToF MS. The approach presented is applicable for a large variety of monomers that are
polymerizable by carbanionic polymerization.
Introduction
(ii) termination of the polymerization with an electrophilic
reagent bearing the desired functionality. Using functional ini-
Carbanionic polymerization is a highly useful technique for the
synthesis of polymers with precisely adjustable molecular weights
and low polydispersity. Its living character along with negligibil-
ity of chain transfer/termination reactions further permits the prep-
aration of specifically chain-end-functionalized polymers. Since
Michael Szwarc’s pioneering works in the 1950s,1 both academic
and industrial interests have been focusing on the exploration of
new synthetic strategies to a large variety of well-defined functional
macromolecules.2 Polymers with functional termini offer vast
potential due to the possibilities resulting from reversible ionic
association, further chain extension, branching, and (cross)linking
with polyfunctional reagents or other polymer chains as well as for
the initiation of subsequent polymerizations. Advanced macromo-
lecular architectures with unique structural and physical proper-
ties3,4 (for instance, block copolymers, comblike, cyclic, linear-
hyperbranched,5 and star-branched polymers) can be elegantly
obtained from well-defined functional polymer precursors.
A large variety of intriguing materials with supramolecular prop-
erties that depend on the nature and position (terminal or in-chain)
of the functional groups has been developed.6 As the interaction at
polymer-polymer interfaces in blends or between polymers and
surfaces can be tailored by the polymer architecture, functional
polymers possess enormous potential for a variety of industrial and
academic applications,7 e.g., dispersion of fillers,8 transparent impact
polystyrene-polybutadiene blends (TIPS),9 and for the modifica-
tion of surface properties, that is, adhesion, wettability, biocompati-
bility, chemical resistance, and hydrophobicity.10
tiators permits quantitative functionalization and facile synthesis
of telechelic polymers with (different) functional groups. How-
ever, their availability is limited, and solubility in solvents suitable
for carbanionic polymerization may sometimes be poor. The
termination strategy (ii) has been employed in most cases. Quirk
and co-workers have optimized the latter approach by realizing a
variety of termination reactions via selective adjustment of
reaction parameters like temperature, solvent, and additives to
obtain a maximum degree of functionalization.11
The most widely used termination reagents are chlorosilane
derivatives.6,12 As an alternative, the reaction with functional
diphenylethylenes (DPE) has become popular,4,13 since the poly-
mer chains remain active for further extension (living function-
alization reaction), unless a termination agent is added. Various
epoxides14 have also been used, particularly ethylene oxide (EO),
however, in fewer cases than the highly established chlorosilane
termination method. Epoxides are of particular interest for the
termination of carbanionic polymerization, since they combine
pronounced chemical versatility with high reactivity toward
nucleophilic attack due to the effect of ring strain. Furthermore,
the lithium counterion common in carbanionic polymerization is
known to prevent further propagation in epoxide polymerization
due to the strong oxygen-lithium aggregation.15 Quirk et al.
took advantage of this behavior in elegant work to realize
quantitatively hydroxyl-terminated polystyrene (PS) by reaction
of the living chain end with ethylene oxide (EO).16 Also, propyl-
ene oxide17 and 1,2-epoxybutane18 have been employed as
termination reagents during the past two decades to introduce a
single secondary hydroxyl group at the chain end. Additional
functionalities can be implemented by using epoxide derivates
with protected or unprotected functional groups, depending on
the stability toward the highly aggressive living carbanions.19,20
Two general strategies are employed to synthesize well-de-
fined, end-functional polymers by living carbanionic polymeri-
zation: (i) use of a (usually protected) functional initiator and/or
*Corresponding author. E-mail: hfrey@uni-mainz.de.
pubs.acs.org/Macromolecules
Published on Web 05/28/2010
r 2010 American Chemical Society

Article
Macromolecules, Vol. 43, No. 13, 2010 5583
Scheme 1. Semicontinuous Synthesis of Multihydroxyl End-Functionalized Polystyrene Using a Microstructured Reactor (HP-IMM)
Glycidyl ethers, a peculiar class of epoxide derivatives, have only
been marginally referred to as termination reagents for living
carbanionic polymerizations. In an elegant work, Hillmyer et al.
reported the termination with methoxy methylene glycidyl ether
(MMO) and subsequent use of the generated bis-hydroxy func-
tional polymer as macroinitiators for preparation of ABC mik-
toarm star terpolymers21 with unusual morphologies.22 In a similar
manner, Huang et al. prepared three-arm star polymers using
ethoxy ethyl glycidyl ether (EEGE) as a termination reagent.23
Here we report on the development of an efficient and versatile
synthesis protocol for the preparation of well-defined polystyrenes
with multiple hydroxyl end groups, using different glycidyl ethers
with acetal structures, namely ethoxy ethyl glycidyl ether (EEGE),
1,2-isopropylidene glyceryl glycidyl ether (IGG), and trans-2-
phenyl-1,3-dioxane glycidyl ether (PDGE) as termination reagents.
In accordance with the rapid approach to precisely defined living
polystyrene chains previously published by our group,24 we employed
a microstructured reaction system25 for sequential initiation/poly-
merization/functionalization within very short times, taking advan-
tage of the dedicated heat and mass transfer characteristics, which
are particularly favorable for living polymerization techniques
requiring rapid mixing of initiator and monomer as well as efficient
heat release due to pronounced exothermic character.24,26
Recent studies demonstrate the successful implementation of
several polymerization techniques in microdimensional devices,
e.g., free radical,27 controlled radical,28 anionic,24,29 and cationic30
polymerizations. Beers et al. performed the anionic polymerization
of styrene in a low-cost aluminum-kapton microfluidic device
investigating different 2D designed flow channels.31 Pertinent
advances have also been achieved in the field of hyperbranched
polymers32 and dendrimers.33
However, only little attention has been paid to the potential of
continuously operating microstructured reactors for the sequential
synthesis of multiple functionalized polymers and the anionic poly-
merization of vinyl monomers with subsequent functionalization in
continuous flow. Within the scope of our investigations, we concen-
trated on the development of a versatile process for the rapid syn-
thesis of novel tailor-made end-functional polymers by living carb-
anionic polymerization, using specifically designed glycidyl ethers
as termination reagents that release multiple hydroxyl groups upon
facile acidic hydrolysis. An overview of the epoxides employed and
the functionalization strategies introduced is shown in Scheme 1.
Tetrahydrofuran (THF) for polymerization was distilled from
sodium/benzophenone under reduced pressure (cryo-transfer).
Styrene was dried over calcium hydride (CaH2) and cryo-trans-
ferred prior to use. sec-Butyllithium (sec-BuLi, 1.3 M, Acros) was
used as received, and the concentration of the initiator was
determined by the Gilman double titration method.34 n-Hexane
and CaH2 were purchased from Fluka and used as received.
Chloroform-d and benzene-d6 were purchased from Deutero
˚
GmbH and stored over molecular sieves (3 A).
Instrumentation. 1H NMR spectra were recorded at 400 MHz
on a Bruker AMX 400 and were referenced internally to residual
proton signals of the deuterated solvent (CDCl3, benzene-d6). Field
desorption mass spectra were measured on a Finnigan MAT 95.
Size exclusion chromatography (SEC) measurements were carried
out in THF on an instrument consisting of a Waters 717 plus
autosampler, a TSP Spectra Series P 100 pump, a set of three PSS
˚
SDV columns (104/500/50 A), and RI and UV detectors. All SEC
diagrams rely on the RI detector signal, and the molecular weights
refer to linear polystyrene (PS) standards provided by Polymer
Standards Service. Matrix-assisted laser desorption and ionization
time-of-flight (MALDI-ToF) measurements were performed on a
Shimadzu Axima CFR MALDI-TOF mass spectrometer using
dithranol (1,8,9-trishydroxyanthracene) as matrix.
Synthesis of Glycidyl Ethers. Ethoxy Ethyl Glycidyl Ether
(EEGE, 1). EEGE was synthesized as reported by Fitton et al.35
Glycidol was added to an excess of ethyl vinyl ether and catalytic
amounts of p-toluenesulfonic acid to obtain the desired product
(yield: 90%).
DL-1,2-Isopropylidene Glyceryl Glycidyl Ether (IGG, 2). IGG
was synthesized according to a recently published procedure36
by phase-transfer reaction of epichlorohydrin and solketal
(isopropylidene glycerol) in benzene and 50% KOH solution
as solvents. Tetrabutylammonium bromide (TBAB) was added
and served as catalyst (yield: 51%).
trans-2-Phenyl-1,3-dioxane Glycidyl Ether (PDGE, 3). 4.1 g
(23 mmol) of 5-hydroxy-2-phenyl-1,3-dioxane (HPD)37 was
dissolved in 20 mL of benzene, 20 mL of 50% KOH, and 0.74 g
(2.3 mmol) of TBAB were added. After cooling the mixture to
10 °C, epichlorohydrin was slowly added via syringe. The
reaction mixture was stirred at room temperature for 48 h,
diluted with diethyl ether, and washed three times with water,
saturated aqueous NaHCO3, and saturated aqueous NaCl.
After drying over MgSO4, diethyl ether and excess epichlorohy-
drin were removed in vacuo. The crude product was purified via
column chromatography (silica, chloroform:ethyl acetate 5:1,
Rf = 0.45). 1.5 g (6.3 mmol, yield: 30%) of PDGE was obtained
and characterized by 1H NMR spectroscopy and field desorp-
tion mass spectrometry (FD-MS). 1H NMR (300 MHz, CDCl3,
Experimental Section
Reagents. All solvents and reagents were purchased from
Acros Organics and used as received unless otherwise stated.

5584 Macromolecules, Vol. 43, No. 13, 2010
Tonhauser et al.
Figure 1. Schematic reactor setup for polymerization of styrene with direct subsequent termination by glycidyl ethers (micromixer: HP-IMM).
δ in ppm): 7.43 (m, 5H, C6H5), 5.57 (s, 1H, CH acetal), 4.37 (m,
2H, CH2 1,3-dioxane), 4.08 (m, 2H, CH2 1,3-dioxane), 3.97 (dd,
1H, CH2 glycidol), 3.55 (q, 1H, CH2 glycidol), 3.46 (m, 1H), 3.24
(m, 1H, CH epoxide), 2.83 (t, 1H, CH2 epoxide), 2.68 (q, 1H,
CH2 epoxide). 13C NMR (75 MHz, CDCl3, δ in ppm): 138.0
(quart. C aromatic), 128.9 (CH aromatic), 128.2 (CH aromatic),
126.1 (CH aromatic), 101.3 (tert. CH acetal), 71.0 (CH 1,3-
dioxane) 69.4 (CH2 1,3-dioxane) 68.6 (CH2), 51.2 (CH epoxide),
44.2 (CH2 epoxide). FD-MS: 235.9 g/mol.
Figure 2. Glycidyl ethers/acetals used as termination reagents in the
continuous polymerization-termination sequences.
Microstructured Reactor. A continuous flow reaction setup
(Scheme 1) equipped with a micromixer was employed for the
synthesis of end-functionalized polystyrenes. A stainless steel
high-pressure slit interdigital micromixer (HP-IMM, provided
diameter, internal volume ∼200 μL) connected to the T-junc-
tion. PS-EEGE-3 was precipitated into methanol and dried in
vacuum at room temperature for 12 h.
All polymer samples prepared have been produced by an
analogous procedure. Adjusting the flow rates via the control
elements of the HPLC pumps or selecting different concentra-
tions permits convenient variation of molecular weights of the
materials prepared.
Synthesis of Multihydroxyl-Functionalized Polystyrene. 500
mg of the end-capped PS was dissolved in 20 mL of THF and
3 mL of 2 M HCl. After refluxing of the solution for 8 h, the
reaction mixture was diluted with chloroform and washed with
saturated aqueous NaHCO3 and water. After drying the organic
phase with MgSO4, all solvents (CHCl3, THF) were removed
under reduced pressure. The samples were precipitated into
MeOH and dried at room temperature for 12 h.
€
by the Institut fur Mikrotechnik Mainz (IMM)) with an internal
volume of 15 μL was used for fast and efficient mixing of
monomer and initiator realized by multilamination mixing
mode, combined with geometric and hydrodynamic focusing.38
The micromixer was immersed in a water bath at predefined
temperature and equipped with two reactant inlets and one
outlet. After mixing of monomer and initiator within several
milliseconds, the reaction mixture passed a short stainless steel
capillary residence tube (for details cf. Figure 1) and was
combined with the corresponding glycidyl ether (separate flow
tube) in a T-junction (diameter = 700 μm). The residence tube
behind the T-junction was connected to a degassed vessel for
sample collection. Flow rates were controlled via HPLC pumps
(Knauer WellChrom K-501, inert 10 mL pump heads with
ceramic inlays).
Results and Discussion
Three different glycidyl ethers (Figure 2) with acetal or ketal
protecting group were used to terminate the living anionic
polystyrene chains in continuous flow, aiming at novel multi-
hydroxyl end-functionalized polymer structures: EEGE (1), IGG
(2), and PDGE (3), a novel glycidyl ether that was prepared from
epichlorohydrin using TBAB as a phase transfer catalyst. This
compound offers the unique possibility to introduce one second-
ary and two primary protected hydroxyl groups via a single
functionalization/deprotection sequence.
The different epoxide termination agents were obtained in high
purity (see Supporting Information, Figures S7 and S8), which is
essential for quantitative chain-end functionalization of living
carbanionic polymers. Strong aggregation of the lithium counter-
ion with alkoxides prevents further oxyanionic propagation,15
rendering the synthesized glycidyl ethers suitable for quantitative
and simultaneous end-capping of the living carbanions.
Synthesis of Hydroxyl-Functionalized Polystyrenes. Exem-
plary Synthesis Procedure for PS-EEGE-3. Prior to the polymeri-
zation reaction, THF was pumped through the microstructured
reactor setup for ∼10 min at 0.5 mL/min via all three HPLC
pumps to rinse off residual impurities. The water bath was kept
at room temperature, and a solution of purified styrene (1.5 M)
in dry THF was kept under argon in a flask covered with a
septum. Into a second flask containing dry hexane, 3.8 mL sec-
BuLi was added via syringe directly before starting the reaction
(0.05 M). The third flask contained a solution of purified EEGE
(0.1 M) in THF. The three flasks were connected to the HPLC
pumps via PTFE tubes transfixed through the septa. The con-
nection tube between micromixer and T-junction was 50 cm in
length and 700 μm in diameter, corresponding to an internal
volume of ∼200 μL. A schematic overview of the general setup is
shown in Figure 1.
Prior to the polymerization start, pump II (initiator) was
activated and the assembly was flushed with sec-BuLi solution
to eliminate residual impurities. In order to initiate the contin-
uous process, pumps I (monomer) and II (initiator) were
activated with flow rates of 1 mL/min. After the characteristic
reddish color appeared at the outlet, pump III was activated
with a flow rate of 1 mL/min to combine the termination reagent
and the reaction mixture within the T-junction. Full monomer
conversion was achieved after 6 s, and the end-capped polymer
was recovered from a short outlet tube (50 cm length, 700 μm
Utilization of the micromixer-based reaction system permits
rapid reactant mixing and offers the possibility to apply reaction
conditions (room temperature) that are not applicable in con-
ventional glass equipment. Thus, significantly faster reaction
kinetics can be realized. The technique is feasible, unless very
high molecular weights are required. The stainless steel setup
shows excellent chemical resistance toward the highly aggressive
carbanions and hence provides an ideal platform for rapid living
anionic polymerization sequences. For comparison, classical

Article
Macromolecules, Vol. 43, No. 13, 2010 5585
Table 1. Characterization Data of End-Functionalized PS Samples
Prepared by Anionic Polymerization with Subsequent Termination in
a Microstructured Reaction Setup
b
c
c
sample
T/°C
ta
Mn
Mn
Mn/Mw
PS-EEGE-1
PS-EEGE-2
PS-EEGE-3
PS-EEGE-4
PS-EEGE-5
PS-EEGE-6
PS-IGG-1
PS-IGG-2
PS-IGG-3
PS-IGG-4
PS-IGG-5
PS-IGG-6
PS-IGG-7
PS-PDGE-1
PS-PDGE-2
PS-PDGE-3
25
40
40
25
40
50
25
60
25
25
25
60
25
25
25
25
12
12
10
5
8
8
1900
1900
3100
4300
3800
3800
1900
2500
2600
3800
3900
5000
5200
2800
5000
7500
1800
1900
3000
3900
4500
6400
1900
2300
2900
4100
5000
5300
7700
3600
4100
8800
1.14
1.15
1.14
1.13
1.26
1.18
1.22
1.18
1.28
1.29
1.21
1.23
1.22
1.26
1.36
1.24
6
12
12
8
10
8
8
12
12
8
Figure 3. MWDs determined via SEC of selected PS-IGG samples
(THF, RI signal).
a Residence time in seconds. b Theoretical value of the number-average
of the molecular weight in g mol-1 c Molecular weight in g mol-1 and
molecular weight distribution characterized by SEC in THF.
.
batch methods for carbanionic polymerizations are often labor-
intensive and in many cases require “high vacuum” or “break-
seal” methods as well as individually manufactured glass reac-
tors.39 Residence times required for full conversion of styrene in
the micromixer-based system are generally below 15 s without
loss of control over the polymerization compared to oftentimes
prolonged reaction times of typically 2-3 h in batch reactors. The
temperature dependency of the continuous flow polymerization
has also been studied by increasing the temperature to 60 °C.
However, no significant deviation with respect to the polymer
properties (Mn, PDI) has been observed.
Initiation of styrene polymerization with sec-BuLi in the
micromixer at room temperature, using THF as a solvent, results
in an extremely fast propagation reaction (t1/2 < 0.5 s).40 Full
monomer conversion is achieved within seconds,24,26 before the
living chain ends are reacted with the unsubstituted carbon of the
highly strained epoxide ring. A short outlet tube (for details cf.
Figure 1) is sufficient for reaction of all living polymer chains with
the termination reagent before leaving the reactor. A color
change of the reaction mixture (reddish to light yellow), resulting
from the termination of living carbanions, can be observed. By
adjusting the ratio of styrene and sec-BuLi flow rates, the degree
of polymerization was readily varied during the ongoing experi-
ment. Thus, the micromixing device provides convenient access
to a variety of structurally different polymers without modifying
the setup within one run. Subsequent to the continuous poly-
merization/functionalization sequence, the protecting groups are
cleaved by acidic hydrolysis to afford multihydroxyl end-func-
tionalized polymers.
Characterization by size exclusion chromatography (SEC)
yielded reasonable agreement between theoretical and experi-
mental molecular weights, revealing narrow to moderate and
monomodal molecular weight distributions (MWDs) (Mw/Mn <
1.30, mostly <1.25; Table 1). No dependence of molecular
weights and PDI on the temperature was observed in the
temperature range between 25 and 60 °C. Figure 3 depicts the
SEC diagrams of IGG-terminated polystyrenes with mono-
modal MWDs, evidencing the remarkable degree of control
over the polymerization under the applied continuous flow
conditions.
Figure 4. 1H NMR spectra of PS-EEGE (bottom: PS-EEGE-2; top:
deprotected PS-EEGE-2 (PS-EEGEd-2); both spectra were measured in
benzene-d6 as solvent.
results in temporary deviations from the adjusted stoichiometry.
Taking into account the significantly reduced experimental effort
using the continuous device, the micromixer-based system pro-
vides an alternative for carbanionic batch polymerization, when
very narrow MWDs with PDIs below 1.05 do not represent a
necessity, as it applies for a wide variety of applications.41
1H NMR spectroscopy was employed to study the functiona-
lization as well as monomer conversion. Figure 4 (bottom)
represents the 1H NMR spectrum of PS-EEGE-2. The expected
signals reflecting the polystyrene backbone (aromatic signals at
7.3-6.3 ppm and aliphatic signals at 2.6-0.8 ppm) are clearly
visible. Referencing the respective signals to the six methyl proton
signals of the initiator sec-BuLi (0.72 ppm) permits to estimate
the functionalization efficiency. The acetalic proton (4.38 ppm)
of the end group attached to the polymer generates a readily
distinguishable signal that can be separately integrated. The
respective values were close to 1 in all cases, indicating a high
degree of functionalization. However, end-group analysis using
1H NMR spectroscopy becomes increasingly problematic at
elevated molecular weights due to the diminishing end-group
signal intensity.
It is known from the literature that the regiochemistry of
reactions between living polystyrene and epoxide compounds
depends on the steric and electronic nature of the termination
reagent.17-20 For instance, the reactions of poly(styryl)lithium
with propylene oxide and 1,2-butene oxide are regioselective
due to pronounced steric effects of the methyl or ethyl group,
The MWDs of the epoxide-terminated polymers obtained by
the continuous approach presented herein are generally slightly
broader than those realizable in classical batch reactors (typi-
cally <1.1, often 1.01-1.03). A possible explanation can be found
in the slightly incontinuous flow of the HPLC pumps, which

5586 Macromolecules, Vol. 43, No. 13, 2010
Tonhauser et al.
hindered carbon atom of EEGE, and thus no primary alcohol
was formed. Furthermore, the 1H-1H-COSY spectrum (see
Supporting Information Figure S5) illuminates the coupling
between b and adjacent methylene groups a and c. Taking into
account the additional steric constraints of the other termination
reagents, similarly regioselective nucleophilic displacement reac-
tions can be safely assumed for all epoxide termination reagents
of this study.
The spectra of both the protected and deprotected polymer
(PS-EEGE-2) are depicted in Figure 4. Complete disappearance
of the acetalic proton d (4.38 ppm) as well as the methyl group
signals (1.06) confirms quantitative deprotection of the acetalic
end groups. It has to be emphasized that the deprotection times are
considerably prolonged compared to water-soluble polymers,42
which can be explained by the nonpolar character of the poly-
styrene backbone, shielding the acetal group from the deprotecting
reagent. Additional NMR spectra of PS-IGG and PS-PDGE
polymers before and after deprotection are given in Figures S3
and S4 of the Supporting Information. As expected, no significant
change in molecular weight and MWD has been observed after
cleavage of the protecting groups (SEC).
As indicated above, NMR spectra cannot provide sufficient
proof for quantitative terminal functionalization of the polymers,
particularly at elevated degrees of polymerization. Matrix-assisted
laser desorption/ionization time-of-flight mass spectrometry
(MALDI-ToF MS) as a crucial characterization method for the
detailed investigation of end-functional polymers was thus applied
in order to obtain unequivocal evidence for the high functionali-
zation efficiency of the method. Quantitative functionalization of
polystyrenes capped with the three different glycidyl ethers was
demonstrated by MALDI-ToF MS, using silver trifluoroacetate
as cationizing agent and dithranol (1,8,9-trishydroxyanthracene)
as matrix. Figure 6 shows two MALDI-ToF spectra of IGG- and
PDGE-terminated polystyrene. The spectrum of PS-IGG (left)
reveals only one distribution mode, which is unambiguously
assigned to IGG-functionalized polystyrene. The most intense
isotopic mass species appear 3 units higher than the monoisotopic
peak, and one representative mass peak at m/z 2541.6 corresponds
to the 21-mer of PS-IGG-3 (C4H9-(C8H8)21-C9H17O4 Agþ);
3
calculated isotopic mass = 2541.4 Da. Similar conclusions apply
for the spectrum on the right, representing PS-PDGE-1 with a
single distribution mode that can clearly be assigned to the desired
polymer. The representative mass peak (28mer: C4H9-(C8H8)21-
Figure 5. Top: section of 1H NMR spectrum of PS-EEGE-2. Bottom:
HSQC spectrum of PS-EEGE-2 after reaction with trifluoroacetic
anhydride (TFAA). Phase information is given by coloration of cross
peaks (red: methyl, methine; blue: methylene).
C13H17O4 Agþ, 3317.7 Da) is in very good agreement with the
3
calculated value (3317.8 Da). In both cases the mass difference
between each signal represents the molecular mass of the mono-
mer (104.1 Da). Furthermore, it has to be emphasized that peaks
corresponding to the protonated, nonfunctional polystyrene
(PS-H: 22mer=2457.4 Da or 31mer=3394.7 Da) are absent in
both spectra, confirming the quantitative functionalization of
polystyrene with IGG and PDGE.
respectively. Nucleophilic attack at the least hindered carbon
atom predominantly results in formation of the secondary
alcohol. In contrast, when employing styrene oxide as a termina-
tion reagent, no regioselectivity can be observed due to the
parallel influence of both steric and electronic effects. In the case
of reacting poly(styryl)lithium with the different glycidyl ethers
reported herein, regioselectivity was expected due to the steric
hindrance of the bulky moieties attached to the epoxide ring.
Two-dimensional (2D) NMR spectroscopy was employed to gain
insight with respect to the selectivity of the reactions. Figure 5
represents a section of the HSQC spectrum of PS-EEGE-2 in
benzene-d6 after reaction with trifluoroacetic anhydride (TFAA),
adding a small amount of pyridine-d5 as acid scavenger to prevent
cleavage of the protecting group. The cross peaks b, generated
by the methine groups, are shifted downfield (5.0-5.5 ppm) in
In order to confirm that nonfunctionalized PS-chains would be
detected in the presence of the functionalized PS-samples, mix-
tures containing end-functional and nonfunctional polystyrenes
have been subjected to MALDI-TOF measurements. In this case,
in 1:1 blends nearly identical detection intensities of both series of
signals were observed (see Supporting Information Figure S9),
and therefore similar desorption and ionization properties of the
different polystyrene types can be safely assumed.
MALDI-ToF investigation of the PS-EEGE sample series
confirmed quantitative functionalization, resulting in analogous
single molecular weight distributions (see Supporting Information
Figure S6). Detailed MALDI ToF studies with the deprotected
1
the corresponding H NMR spectrum due to ester formation.
Owing to the presence of a mixture of diastereomers, two distinct
methine signals are generated. The absence of any downfield-
shifted methylene signals (blue) indicates that regioselective
attack of poly(styryl)lithium took place exclusively at the least
1
polymers confirmed results of the H NMR spectra, evidencing
successful cleavage of the protecting groups and full functionaliza-
tion (see Supporting Information Figure S6).

Article
Macromolecules, Vol. 43, No. 13, 2010 5587
Figure 6. MALDI-ToF mass spectra of end-functionalized polystyrene synthesized in continuous flow: PS-IGG-3 (left), PS-PDGE-1 (right).
Conclusion
Chemischen Industrie (FCI) for a Ph.D. fellowship. We also
€
thank the IMM (Institut fur Mikrotechnik Mainz) for pro-
viding the micromixer equipment.
We have developed a semicontinuous strategy for the rapid
preparation of multihydroxyl-functional polystyrenes, capitaliz-
ing on the high stability of the acetal-protecting groups of the
protected glycidyl ethers toward strong bases. The synthetic
approach presented relies on a continuously operating micro-
structured reaction device for living carbanionic polymerization
and termination with specifically tailored glycidyl ethers, fol-
lowed by deprotection of the introduced end-group moieties.
Adjustment of molecular weights as well as chemical nature of
the end group can be achieved by alteration of the flow rates in a
single experiment without interrupting the continuous flow
process. Full styrene monomer conversion was achieved within
several seconds by working at room temperature in a polar
solvent, usually THF. The functional polymers were thus ob-
tained in very short reaction times without having to resort to
tedious postpolymerization protocols or purification steps in
order to yield pure and quantitatively functionalized materials.
The acetal and ketal protecting groups of the employed termina-
tion reagents are stable toward the highly reactive carbanions and
can be cleaved under acidic conditions.
Supporting Information Available: Additional data, MAL-
DI-ToF, NMR, and SEC results (Figures S1-S9, Table 1)
demonstrating monomodal molecular weight distributions
and complete functionalization. This material is available free
of charge via the Internet at http://pubs.acs.org.
References and Notes
(1) Szwarc, M. Nature 1956, 178, 1168–1169.
(2) Quirk, R. P.; Pickel, D. L. Anionic Synthesis of Chain-End
Functionalized Polymers. Scope, Limitations and Recent Ad-
vances. In Living and Controlled Polymerization; Jagur-Grodzinski,
J., Ed.; Nova Science Publishers: Hauppauge, NY, 2006; pp 235-255.
(3) Hadjichristidis, N.; Iatrou, H.; Pitsikalis, M.; Mays, J. Prog.
Polym. Sci. 2006, 31, 1068–1132.
(4) (a) Hirao, A.; Hayashi, M. Acta Polym. 1999, 50, 219–231.
(b) Higashihara, T.; Sugiyama, K.; Yoo, H.-S.; Hayashi, M.;
Hirao, A. Macromol. Rapid Commun. 2010, DOI: 10.1002/
marc.200900773.
(5) (a) Marcos, A. G.; Pusel, T. M.; Thomann, R.; Pakula, T.; Okrasa,
L.; Geppert, S.; Gronski, W.; Frey, H. Macromolecules 2006, 39,
971–977. (b) Barriau, E.; Marcos, A. G.; Kautz, H.; Frey, H. Macromol.
Rapid Commun. 2005, 26, 862–867. (c) Wurm, F.; Nieberle, J.; Frey, H.
Macromolecules 2008, 41, 1184–1188.
(6) Hadjichristidis, N.; Pitsikalis, M.; Pispas, S.; Iatrou, H. Chem. Rev.
2001, 101, 3747–3792.
(7) Quirk, R. P.; Gomochak, D. L. Rubber Chem. Technol. 2003, 76,
812–831.
(8) Quirk, R. P.; Jiang, K. Polym Prepr. (Div. Polym. Chem.) 2001, 42,
27–28.
(9) Kobatake, S.; Harwood, H. J.; Quirk, R. P.; Priddy, D. B. Macro-
molecules 1998, 31, 3735–3739.
(10) Hutchings, L. R.; Narrianen, A. P.; Thompson, R. L.; Clarke, N.;
Ansari, I. Polym. Int. 2008, 57, 163–170.
(11) Quirk, R. P.; Hsieh, H. L. Functionalized Polymers and Macro-
monomers. In Anionic Polymerization: Principles And Practical
Applications; Hudgin, D. E., Ed.; Marcel Dekker: New York, 1996;
pp 261-306.
(12) Peters, M. A.; Belu, A. M.; Linton, R. W.; Dupray, L.; Meyer, T. J.;
DeSimone, J. M. J. Am. Chem. Soc. 1995, 117, 3380–3388.
(13) Quirk, R. P.; Yoo, T.; Lee, Y.; Kim, J.; Lee, B. Application of
1,1-Diphenylethylene Chemistry in Anionic Synthesis of Polymers
with Controlled Structure. In Advances in Polymer Science; Springer-
Verlag: Berlin, 2000; Vol. 153, pp 67-162.
The general termination methodology presented herein also
provides a method for rapid and cost-efficient polymer screening
with respect to novel end-functionalized materials. By tailoring
the glycidyl ethers by means of standard organic synthesis
protocols, a large variety of terminal units at vinyl polymers with
multiple end groups and intriguing properties can be realized.
The respective materials can be further used as macroinitiators
for complex macromolecular architectures, such as miktoarm
star polymers, block copolymers, and graft polymers. Depending
on monomer and termination reagent, such end-functional
polymers are also promising for the specific adjustment of sur-
face and interfacial properties. Use of several monomer/termina-
tion reagent combinations can rapidly afford polymer libraries,
permitting to screen a wide range of material properties
(wettability, hydrophobicity, chemical resistance, biocompati-
bility). A detailed study of other carbanionic polymerization
reactions with respect to protected glycidyl ether termination and
functionalization is currently in progress and will be reported in
due course.
Acknowledgment. C.T. thanks the POLYMAT Graduate
Class of Excellence as well as MPGC (Max Planck Graduate
Center with Johannes Gutenberg University) for fellowships
and financial support. D.W. acknowledges the Fonds der
(14) Quirk, R. P.; Cheong, T. H.; Jiang, K.; Gomochak, D. L.; Yoo,
T. J.; Andes, K. T.; Mathers, R. T. Macromol. Symp. 2003, 195,
69–74.

5588 Macromolecules, Vol. 43, No. 13, 2010
Tonhauser et al.
(15) Furukawa, J.; Saegusa, T.; Tsuruta, T.; Kakogawa, G. Macromol.
Chem. Phys. 1960, 36 (1), 25–39.
(16) Quirk, R. P.; Ma, J. J. J. Polym. Sci., Part A: Polym. Chem. 1988,
26, 2031–2037.
(17) Quirk, R. P.; Lizarraga, G. M. Macromolecules 1998, 31, 3424–
3430.
(18) Quirk, R. P.; Ge, Q.; Arnould, M. A.; Wesdemiotis, C. Macromol.
C.; Beers, K. L. J. Am. Chem. Soc. 2004, 126, 9880–9881. (c) Wu, T.;
Mei, Y.; Xu, C.; Byrd, H. C. M.; Beers, K. L. Macromol. Rapid
Commun. 2005, 26, 1037–1042.
(29) (a) Miyazaki, M.; Honda, T.; Nakamura, H.; Maeda, H. Chem.
Eng. Technol. 2007, 30, 300–304. (b) Nagaki, A.; Tomida, Y.;
Miyazaki, A.; Yoshida, J.-I. Macromolecules 2009, 42, 4384–4387.
(30) (a) Nagaki, A.; Kawamura, K.; Suga, S.; Ando, T.; Sawamoto,
M.; Yoshida, J.-I. J. Am. Chem. Soc. 2004, 126, 14702–14703.
(b) Iwasaki, T.; Nagaki, A.; Yoshida, J.-I. Chem. Commun. 2007,
1263–1265. (c) Iwasaki, T.; Yoshida, J.-I. Macromol. Rapid Commun.
2007, 28, 1219–1224. (d) Ouchi, M.; Inagaki, N.; Ando, T.; Sawamoto,
M. Polym. Prepr. (Div. Polym. Chem.) 2005, 46, 939–940.
(31) Iida, K.; Chastek, T. Q.; Beers, K. L.; Cavicchi, K. A.; Chun, J.;
Fasolka, M. J. Lab Chip 2009, 9, 339–345.
Chem. Phys. 2001, 202, 1761–1767.
(19) Quirk, R. P.; Gomochak, D. L.; Wesdemiotis, C.; Arnould, M. A.
J. Polym. Sci., Part A: Polym. Chem. 2003, 41 (7), 947–957.
(20) Quirk, R. P.; Hasegawa, H.; Gomochak, D. L.; Wesdemiotis, C.;
Wollyung, K. Macromolecules 2004, 37, 7146–7155.
(21) (a) Li, Z.; Hillmyer, M. A.; Lodge, T. P. Macromolecules 2004, 37,
8933–8940. (b) Saito, N.; Liu, C.; Lodge, T. P.; Hillmyer, M. A.
Macromolecules 2008, 41, 8815–8822.
€
(32) Wilms, D.; Nieberle, J.; Klos, J.; Lowe, H.; Frey, H. Chem. Eng.
(22) (a) Li, Z.; Kesselman, E.; Talmon, Y.; Hillmyer, M. A.; Lodge,
T. P. Science 2004, 306, 98–101. (b) Li, Z.; Hillmyer, M. A.; Lodge,
T. P. Langmuir 2006, 22, 9409–9417.
Technol. 2007, 30, 1519–1524.
(33) Liu, S.; Chang, C.-H. Chem. Eng. Technol. 2007, 30, 334–340.
(34) Gilman, H.; Haubein, A. H. J. Am. Chem. Soc. 1944, 66, 1515–
(23) Wang, G.; Huang, J. J. Polym. Sci., Part A: Polym. Chem. 2008, 46,
1136–1150.
1516.
(35) Fitton, A. O.; Hill, J.; Jane, D. E.; Millar, R. Synthesis 1987, 1140–
€
(24) Wurm, F.; Wilms, D.; Klos, J.; Lowe, H.; Frey, H. Macromol.
1142.
Chem. Phys. 2008, 209, 1106–1114.
(25) (a) Hessel, V.; Renken, A.; Schouten, J. C.; Yoshida, J.-I. Micro
(36) Wurm, F.; Nieberle, J.; Frey, H. Macromolecules 2008, 41, 1909–
1911.
(37) Carlsen, P. H. J.; Sorbye, K.; Ulven, T.; Aasbo, K. Acta Chem.
Process Engineering: A Comprehensive Handbook; Wiley-VCH:
€
€
Weinheim, 2009. (b) Jahnisch, K.; Hessel, V.; Lowe, H.; Baerns, M.
Angew. Chem., Int. Ed. 2004, 43, 406–446. (c) Wilms, D.; Klos, J.;
Frey, H. Macromol. Chem. Phys. 2008, 209, 343–356. (d) Hessel, V.;
Scand. 1996, 50, 185–187.
€
€
(38) Hessel, V.; Hardt, S.; Lowe, H.; Schonfeld, F. AlChE J. 2003, 49,
566–577.
(39) Hadjichristidis, N.; Iatrou, H.; Pispas, S.; Pitsikalis, M. J. Polym.
€
Lowe, H.; Serra, C.; Hadziioannou, G. Chem. Ing. Tech. 2005, 77,
1693–1714.
Sci., Part A: Polym. Chem. 2000, 38, 3211–3234.
(26) Nagaki, A.; Tomida, Y.; Yoshida, J.-I. Macromolecules 2008, 41,
6322–6330.
(27) (a) Iwasaki, T.; Yoshida, J.-I. Macromolecules 2005, 38, 1159–1163.
(b) Serra, C.; Sary, N.; Schlatter, G.; Hadziioannou, G.; Hessel, V. Lab
Chip 2005, 5, 966–973.
(40) (a) Geacintov, C.; Smid, J.; Szwarc, M. J. Am. Chem. Soc. 1962, 84,
2508–2514. (b) Bhattacharyya, D. N.; Lee, C. L.; Smid, J.; Szwarc, M.
J. Am. Chem. Soc. 1963, 85, 533–539. (c) Bhattacharyya, D. N.; Lee,
C. L.; Smid, J.; Szwarc, M. J. Phys. Chem. 1965, 69, 612–623.
(41) Lynd, N. A.; Hillmyer, M. A. Macromolecules 2005, 38, 8803–8810.
(42) Mangold, C.; Wurm, F.; Obermeier, B.; Frey, H. Macromol. Rapid
Commun. 2010, 31, 258–264.
(28) (a) Rosenfeld, C.; Serra, C.; Brochon, C.; Hadziioannou, G. Chem.
Eng. Sci. 2007, 62, 5245–5250. (b) Wu, T.; Mei, Y.; Cabral, J. T.; Xu,