Poly(ethylene glycol)-block-poly(N-vinylformamide) copolymers synthesized by the RAFT methodology

Article abstract of DOI:10.1021/ma025670z

The radical polymerization of N-vinylformamide was followed and found to proceed in a controlled manner if an appropriate RAFT agent is employed. Use of a poly(ethylene glycol) macro-RAFT agent allowed for the generation of block copolymers of PEG and PNVF.

Full text of DOI:10.1021/ma025670z

Macromolecules 2003, 36, 2563-2567
2563
radical then continues polymerization. The equilibrium
is established by subsequent chain transfer-fragmenta-
tion steps between the propagating radicals and poly-
meric RAFT agents and continues until all monomer is
consumed, resulting in controlled growth of chains.
P oly(eth ylen e
glycol)-block-p oly(N-vin ylfor m a m id e)
Cop olym er s Syn th esized by th e RAF T
Meth od ology
The RAFT method is a very convenient tool for
preparation of block copolymers. The sequential polym-
erization of two monomers has given a number of
copolymers such as poly(styrene-b-methyl methacry-
late)16 and poly(sodium 4-styrenesulfonate)-b-poly(so-
dium 4-vinylbenzoate).17 In the present paper, we
describe the synthesis and characterization of a new
PEG macro-RAFT agent containing a xanthate end
group and its application in the synthesis of PEG-block-
PNVF copolymer. We focused on the use of the RAFT
method after our attempts to employ ATRP methodology
with NVF were unsuccessful.
Lia n ju n Sh i,† Toby M. Ch a p m a n ,‡ a n d
Er ic J . Beck m a n *,†
Department of Chemical and Petroleum Engineering and
Department of Chemistry, University of Pittsburgh,
Pittsburgh, Pennsylvania 15261
Received September 12, 2002
Revised Manuscript Received J anuary 20, 2003
Block copolymers where one block is poly(ethylene
glycol) (PEG) are of interest in diverse applications
ranging from commodity surfactants to biocompatible
scaffolds for tissue engineering. PEG has many inter-
esting physicochemical properties such as hydrophilic-
ity1 and solubility in both water and common organic
solvents. Its biological properties include a lack of
toxicity, antigenicity, and immunogenicity.2-4 As such,
investigation of new PEG-based block copolymers is
continuing in both academia and industry.
Poly(N-vinylformamide) (PNVF) is a novel water-
soluble polymer that,5 because of previous monomer
purification problems, has not received wide attention
until recently. PNVF is not only a water-soluble polymer
but also as an important precursor for preparing poly-
(vinylamine). To date, PNVF and its derivatives have
been used in water treatment,6 papermaking, and
radiation cure coating.7,8 Little published work exists
regarding block copolymers containing NVF.
Exp er im en ta l Section
Ma ter ia ls. N-Vinylformamide was donated by BASF AG
and distilled under reduced pressure before use. All other
reagents used in this work were purchased from Aldrich. 4,4′-
Azobis(4-cyanopentanoic acid) and 1,1′-azobis(cyclohexanecar-
bonitrile) (VAZO-88) were purified by recrystallization from
methanol and ethanol, respectively. PEG monomethyl ether
(MeOPEG) (Mn ) 2000, Mw/Mn ) 1.09 and Mn ) 5000, Mw/Mn
) 1.04) was dried in a vacuum at 40 °C for 24 h. All other
reagents, including potassium ethyl xanthate, iodine, potas-
sium iodide, and dicyclohexylcarbodiimide (DCC), were ana-
lytical grade and used as received. All solvents were purified
using common methods.
4-Cyano-4-((thioethoxyl)sulfanyl)pentanoic acid was pre-
pared according to the method described by Zard et al.18 in
53% yield. IR (cm-1): 3400-2500 (COO-H), 2235 (-CN), 1713
1
Traditionally, block copolymers are made by anionic,9
cationic,10 and group-transfer polymerization methods;11
however, these polymerization methods can be success-
fully carried out only under controlled conditions (such
as low temperature, inert atmosphere, or carefully
purified monomers) and only for a limited number of
monomers. NVF is not directly suitable for anionic and
group transfer polymerization, while only oligomer is
obtained via cationic polymerization.12 Over the previ-
ous decade several types of living (controlled) free
radical polymerization have been developed, enhancing
our ability to easily generate block copolymers through
sequential monomer addition. The most three common
types of living radical polymerization systems are (1)
stable free radical polymerization (SFRP) using nitrox-
ides such as 2,2,6,6-tetramethyyl-1-piperdinyloxynitrox-
ide,13 (2) atom transfer radical polymerization (ATRP)
using a transition metal complex, or (3) reversible
addition-fragmentation chain transfer polymerization
(RAFT) using dithioesters as chain transfer agents
(RAFT agent).14,15 The latter has proven to be a versatile
method for controlled radical polymerization of a variety
of monomers including vinyl acetate. The mechanism
involves the chain transfer of active species such as the
radicals from decomposition of the initiator and propa-
gating polymer radicals to the RAFT agent, forming an
unreactive adduct radical, followed by fast fragmenta-
tion to a polymeric RAFT agent and a new radical. The
(CdO), 1040 (CdS). H NMR (CDCl3): δ 1.45 (t, CH3CH2O-,
3H), 2.18 (s, -C(CH3)(CN)-, 3H), 2.36 (2 t, -CH2CH2COOH,
2H), 2.6 (t, -CH2CH2COOH, 2H), 4.75 (q, CH3CH2O-, 2H).
Syn th esis of O,O-Dieth yl Bisxa n th a te (2). O,O-Diethyl
bisxanthate (2) was prepared by a method derived from that
of Houben.19 Potassium ethyl xanthate (1) (10.86 g, 0.067 mol)
was dissolved in deionized water (50 mL), and the solution
was transferred to a 500 mL Erlenmeyer flask equipped with
a magnetic stir bar. Aqueous 10% iodine/potassium iodide
solution (50 mL) was added dropwise to the xanthate solution
via a dropping funnel over 30 min with strong stirring. The
reaction mixture was allowed to stand overnight. Water (80
mL) was then added to the mixture, and the product was
extracted with ether (3 × 60 mL). The combined ether extracts
were washed with water (2 × 100 mL) and then with brine
(100 mL). The resulting solution was dried over anhydrous
MgSO4 overnight. The product was recovered by evaporating
the ether, and it crystallized to a solid mass on cooling. The
yield was 84% (6.90 g, 0.028 mol). 1H NMR (CDCl3): δ 1.45 (t,
CH3CH2O-, 6H); 4.75 (q, CH3CH2O-, 4H).
Syn th esis of ω-Meth oxy-r-[4-cya n o-4-((th ioeth oxyl)-
su lfa n yl)p en ta n oyl]P EGs (5a ,b). MeOPEG (Mn ) 2000, 13.7
g, 6.84 mmol) was dissolved in 250 mL of ethyl acetate.
4-Cyano-4-((thioethoxyl)sulfanyl)pentanoic acid (4.23 g, 17
mmol) and DCC (3.52 g, 17 mmol) were added. After stirring
at room temperature for 24 h, the precipitated dicyclohexy-
lurea was removed by filtering. The remaining solution was
placed in the refrigerator at 0 °C for 24 h, and the product
was obtained by collecting the crystals and drying at 40 °C
under vacuum. The yield was 94% (14.3 g). The product (5a )
has Mn ) 2100 and Mn/Mw ) 1.09. Characterization: 1H NMR
(CDCl3): δ 3.6 (-OCH2CH2O-); 3.9 (OCH2CH2OC(dO); 4.3
(-OCH2CH2OC(dO)-); 4.7 (-SC(dO)OCH2CH3). GPC: Mn )
2100, Mn/Mw ) 1.09. The other ω-methoxy-R-[4-cyano-4-
† Department of Chemical and Petroleum Engineering.
‡ Department of Chemistry.
10.1021/ma025670z CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/11/2003

2564 Notes
Macromolecules, Vol. 36, No. 7, 2003
F igu r e 1. IR spectra of 4-cyano-4-((thioethoxyl)sulfanyl)pentanoic acid (A, upper) and PEG (Mn ) 2000) after capping with it
(B, lower).
Sch em e 1. Syn th esis of P EG Ma cr o-RAF T Agen t
100 °C for 30 min. To control the reaction accurately, the
system was quickly frozen with liquid nitrogen after the given
polymerization time. The product was diluted with water
containing 10% ethanol (v/v) and precipitated from acetone.
The copolymer was precipitated from DMSO into ether and
then purified with diethyl ether in Soxhlet extraction for 8 h
and then in ethyl acetate for 4 h to remove possible unreacted
PEG. However, we only find a negligible amount of PEG
during purification. The product was dried under vacuum at
40 °C for 24 h. The resulting copolymer was 0.38 g (NVF
conversion: 12%). Characterization: 1H NMR (D2O): δ1.7
(broad, -CH2-CH (NH-)-); 3.3 (broad, -CH2-CH(NH-)-);
3.6 (broad, -CH2CH2O-); 3.9 (broad, -NHCH(CdO); 8.0
(broad, -NHCH(CdO)).
Mea su r em en ts. IR spectra were recorded on a Nicolet 360
FT-IR spectrometer. 1H NMR spectra were recorded on a
Bruker MSL-300, using deuterium oxide or CDCl3 as solvent
and tetrmethylsilane as internal standard. UV spectra were
taken on Perkin-Elmer Lambda 2 UV spectrometer. Vapor
pressure osmometry (VPO) measurements for Mn determina-
tion were made with a vapor pressure osmometer, OSMOMAT
070-SA (Gonotec. Co) (cell temperature ) 40 °C, solvent )
double distilled water). An aqueous gel permeation chromato-
graph (GPC) for the characterization of Mn of block copolymer
consisted of HPLC components from Waters Corp. (model 515
pump, detector: Viscotek triple detector array (TDA): model
300). The column was a Waters Ultrahydrogel (PEO) (pore
size: 250 Å, exclusion limits: 8 × 104, length: 7.8 mm × 300
mm). An aqueous mobile phase was used consisting of 0.1 M
NaNO3 and 0.01% NaN3 at a flow rate of 1.0 mL/min at 35
°C. Conversion was determined gravimetrically.
((thioethoxyl)sulfanyl)pentanoyl]PEG (Mn ) 5000) was pre-
pared using a similar procedure (yield: 90%). The product (5b)
has Mn ) 5200 and Mn/Mw ) 1.04.
Syn th esis of P EG-P NVF Block Cop olym er s. A stock
solution in DMSO containing (R-[4-cyano-4-((thioethoxyl)-
sulfanyl)pentanoyl]PEG (6.2 × 10-2 M), N-vinylformamide (7.3
M), DMSO, and initiator VAZO-88 (7.0 × 10-3 M) was
prepared. In a typical experiment, a 2 mL aliquot of the stock
solution (0.124 mmol or 0.26 g of compound 5a , 14.6 mmol or
1.04 g of NVF, and 0.014 mmol or 0.004 g of VAZO-88) was
added to an ampule. Before sealing, the contents were carefully
degassed by three freeze-pump-thaw cycles under oil pump
vacuum. The polymerization was carried out in an oil bath at
Resu lts a n d Discu ssion
Syn t h esis of ω-Met h oxy-r-[4-cya n o-4-((t h io-
et h oxyl)su lfa n yl)p en t a n oyl]P E Gs (P E G Ma cr o-
RAF T Agen ts). The key to successful RAFT polymer-

Macromolecules, Vol. 36, No. 7, 2003
Notes 2565
F igu r e 2. 1H NMR spectrum recorded in CDCl3 for 4-cyano-4-((thioethoxyl)sulfanyl)pentanoic acid (A, upper) and PEG
(Mn ) 2000) after capping with it (B, lower).
Ta ble 1. P r ep a r a tion a n d Ch a r a cter iza tion of ω-Meth oxy-
r-[4-cya n o-4-((th ioeth oxyl)su lfa n yl)p en ta n oyl]P EGs
ization is the choice of an effective thiocarbonylthio
reagent for each monomer. For example, the polymer-
ization of vinyl acetate is completely inhibited in the
presence of dithioesters, trithiocarbonates, and aromatic
dithiocarbamates,20 the preferred RAFT agents for
methacrylates, acrylamides, and styrene. But xanthates
and aliphatic dithiocarbamates, which show little or no
activity with these monomers, function effectively in the
RAFT polymerization of vinyl acetate.20 Chong et al.
synthesized a poly(styrene)-PEG block copolymer suc-
cessfully by using ω-methoxy-R-[4-cyano-4-((thioben-
zoyl)sulfanyl)pentanoyl]PEG.21 Because N-vinylforma-
mide exhibits reactivity characteristics and molecular
structure similar to vinyl acetate,22 we chose the xan-
thate type as the RAFT agent for this study.
MeOPEG
macro-RAFT
agents
capping efficiency
Mn
×
yield
(%)
10-3 a
Mn/Mw
UV
NMR
0.92
5a
5b
2
5
1.09
1.04
94
90
1.00
0.98
a
Mn’s of starting MeOPEG’s.
(λ ) 294 nm) was used.23 We also calculated the capping
efficiency of the xanthate group on PEG with molecular
weight (Mn ) 2000) by comparing the peak area of the
methyl protons of 4-cyano-4-((thioethoxyl)sulfanyl)pen-
tanoic acid fragment at 1.8 ppm and the methylene
protons of the PEG chain at the 3.6 ppm. Table 1
summarizes the characterization results of ω-methoxy-
R-[4-cyano-4-((thioethoxyl)sulfanyl)pentanoyl]PEGs. This
approach to forming the macro-RAFT agent is relatively
efficient. Further, it is likely that this strategy could
be used to form a variety of macro-RAFT agents, as it
could easily be generalized to any number of precursor
polymers with terminal OH groups.
The O-ethylxanthate group was attached to the end
of MeOPEG (PEG with one terminal methoxy and one
terminal hydroxy group) by the capping reaction of
4-cyano-4-((thioethoxyl)sulfanyl)pentanoic acid and
MeOPEG in ethyl acetate in the presence of DCC
(Scheme 1). ω-Methoxy-R-[4-cyano-4-((thioethoxyl)sul-
1
fanyl)pentanoyl]PEGs were characterized by IR and H
NMR spectra. Figure 1 shows the IR spectra of 4-cyano-
4-((thioethoxyl)sulfanyl)pentanoic acid (A) and the prod-
uct following esterification with MeOPEG (Mn ) 2000
(B)). The spectra confirm the formation of the ester
carbonyl group with the appearance of a new band at
1730 cm-1 and disappearance of the original carbonyl
group at 1713 cm-1. The large band at 1040 cm-1
represents the characteristic peak of CdS. In the 1H
NMR spectrum (Figure 2B), typical signals of both PEG
and new end group were detected. New resonances at
3.9 ppm (OCH2CH2OC(dO)) and 4.3 ppm (-OCH2CH2-
OC(dO)) also confirm the formation of the ester group.
The peaks at 4.7, 2.6, 2.4, 1.7, and 1.5 ppm represent
protons of the 4-cyano-4-((thioethoxyl)sulfanyl)pentanoic
acid fragment.
P r ep a r a t ion a n d Ch a r a ct er iza t ion of P E G-
P NVF Block Cop olym er s. The experimental results
of the polymerization of N-vinylformamide in the pres-
ence of PEG macro-RAFT agents with different molec-
ular weights are given in Table 2. Table 2 illustrates
that the molecular weight of PNVF block copolymer and
the conversion of the NVF monomer increased linearly
with the polymerization time. This indicates that po-
lymerization of NVF occurs from one end of PEG via a
controlled radical polymerization as described by Riz-
zardo et al.,15 resulting in the formation of PEG-PNVF
block copolymers (Scheme 2). The broad polydispersities
of NVF block copolymers might be attributed to the
greater chain transfer of N-vinylformamide propagating
radical to monomer and polymer.24,25 The chain transfer
constant of N-vinylformamide is CM ) 9.53 × 10-4 at
60 °C,24 which is higher than that of common monomers
such as vinyl acetate (CM ) (1.75-2.85) × 10-4), styrene
The capping efficiency of the xanthate group on PEG
could be obtained from the UV and/or NMR spectra. For
a quantitative determination of the capping efficiency
of the xanthate group on PEG, a calibration curve based
on 4-cyano-4-((thioethoxyl)sulfanyl)pentanoic acid

2566 Notes
Macromolecules, Vol. 36, No. 7, 2003
Ta ble 2. Molecu la r Weigh t a n d Con ver sion Da ta for P EG-P NVF Cop olym er sa P r ep a r ed in th e P r esen ce of P EG
Ma cr o-RAF T Agen t in DMSO a t 100 °C
c
d
e
no. of block copolymerb
time (h)
Mn × 10-3
Mn × 10-3
Mn × 10-3
Mw/Mn
conv of NVF (%)
1
2
3
4
0.5
1
2
5.2 (3.2)f
9.2 (7.2)f
11.5 (9.5)f
8.7 (3.7)f
5.8 (3.8)f
6.1 (4.1)f
1.7
13
32
45
10
10.4 (8.4)f
9.2 (4.2)f
1
9.8 (4.8)f
2.3
a
Polymerization conditions: [NVF] ) 7.3 M, [PEG macro-RAFT agent] ) 6.2 × 10-2 M, [VAZO-88] ) 7.0 × 10-3 M for making samples
1-3 and 3.0 × 10-3 M for sample 4. Samples 1-3 and 4 were prepared using PEG macro-RAFT agent with a molecular weight of 2000
b
(5a ) and 5000 (5b), respectively. c Molecular weight was calculated from 1H NMR data of block copolymer. Molecular weight was
d
determined via VPO. e Molecular weight was determined via GPC. f Parentheses show molecular weight (×10-3) of PNVF block, which
was calculated from the difference in Mn before and after the polymerization.
F igu r e 3. IR spectrum of PEG-PNVF block copolymer (Mn ) 6.1 × 103, Mw/Mn ) 1.7).
F igu r e 4. 1H NMR spectrum recorded in D2O for PEG-PNVF block copolymer (Mn ) 6.1 × 103, Mw/Mn ) 1.7).
(CM ) (0.3-0.6) × 10-4), and methyl methacrylate
the molecular weight of the PEG is high or low. Also,
the yield and Mn of the poly-NVF parallel the reaction
time, indexing for initiator concentration. This is ad-
ditional evidence that the polymerization follows the
controlled mode.
(CM ) (0.07-0.25) × 10-4).26
In addition, samples 1 and 4 have almost identical
PNVF lengths under the same ratios of [NVF] to [macro-
RAFT agent] at similar monomer conversions, whether

Macromolecules, Vol. 36, No. 7, 2003
Notes 2567
shown in Figure 4. Peaks at 8.0 ppm (e), 3.9 and 3.3
ppm (c), and 1.7 ppm (b) also confirmed the formation
of PNVF block. The peak at 3.6 ppm (a) is the charac-
teristic peak of the protons of the PEG chain.
Figure 5 shows GPC chromatograms for the block
copolymer made from MeOPEG (Mn ) 2000) macro-
RAFT agent (curve B), in which only one peak appeared
after purification, as compared to the GPC trace for the
PEG precursor (curve A). This further indicates that
PEG-PNVF block copolymer, rather than homopolymer
of NVF, was produced during the polymerization.
In summary, we have shown that the radical polym-
erization of N-vinylformamide can proceed in a con-
trolled manner if an appropriate RAFT agent is em-
ployed. Use of a poly(ethylene glycol) macro-RAFT agent
allowed for the generation of block copolymers of PEG
and PNVF.
Ack n ow led gm en t. The authors thank the PTIA
program of the Commonwealth of Pennsylvania for
support of this program.
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agent (Mn ) 2.1 × 103, Mw/Mn ) 1.09) (A) and PEG-PNVF
copolymer (Mn ) 6.1 × 103, Mw/Mn ) 1.7) (B) after purification.
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1
1112 (CH2-O-CH2) wavenumbers. A typical H NMR
spectrum of purified PEG-NVF block copolymer is
MA025670Z