Norbornenyl-based RAFT agents for the preparation of functional polymers via thiol-ene chemistry

Article abstract of DOI:10.1021/ma200799b

A synthetic platform for the preparation of various norbornenyl (Nb) containing reversible addition-fragmentation chain transfer (RAFT) agents has been developed. The design of the chain transfer agents (CTAs) is based on the desymmetrization of α,α′-dibr

Full text of DOI:10.1021/ma200799b

ARTICLE
pubs.acs.org/Macromolecules
Norbornenyl-Based RAFT Agents for the Preparation of Functional
Polymers via ThiolꢀEne Chemistry
Milan M. Stamenoviꢀc, Pieter Espeel, Wim Van Camp, and Filip E. Du Prez*
Polymer Chemistry Research Group, Department of Organic Chemistry,Ghent University, Krijgslaan 281 (S4-bis),
9000 Ghent, Belgium
S Supporting Information
b
ABSTRACT:
A synthetic platform for the preparation of various norbornenyl (Nb) containing reversible additionꢀfragmentation chain transfer
(RAFT) agents has been developed. The design of the chain transfer agents (CTAs) is based on the desymmetrization of
R,R0-dibromo-p-xylene by monosubstitution with an alkoxide anion and subsequent replacement of the residual bromine atom in
the benzylic bromide to create several series of RAFT CTA including trithiocarbonate, xanthate and dithiobenzoate CTAs, allowing
for the possibility to introduce other functional groups besides Nb, such as an allyl group. While a norbornene functionality was
chosen as most reactive functional group toward thiols in radical-mediated thiolꢀene chemistry, an allyl group was introduced for
the sake of direct comparison of the double bond reactivity in the thiolꢀene reaction. Control of the radical polymerization of
acrylates, styrene and vinyl acetate has been achieved by using this novel family of CTAs. The results indicate that the Nb group
remained intact at low monomer conversions (e.g., below 50% for styrene and vinyl acetate, below 30% for acrylates) and at optimal
reaction temperatures (e.g., 70 °C for styrene and vinyl acetate, 62 and 65 °C for 1-ethoxyethyl acrylate and methyl acrylate,
respectively), while the monomer-to-CTA ratio was kept high. Polymers with high end-group fidelity were modified with a series of
thiol-containing compounds, leading to R-semitelechelics with different chain-end structures. While allyl-containing polymers
exhibited a significantly lower reactivity, modification of the Nb-containing semitelechelics was rapid and fully accomplished under
the same reaction conditions. However, for the given conditions, dodecanethiol and benzyl mercaptan showed a lower reactivity
toward Nb-containing polymers, as evidenced by the obtained modification efficiency of 70% and 45%, respectively.
’ INTRODUCTION
synthesis of well-defined polymers with regard to chain length
and desired architecture, while maintaining a specific end group
functionality that allows further postpolymerization modifica-
tions. Telechelic polymers10 and, more specifically, semiteleche-
lic functional polymers denote the simplest family of functional
polymers, but are nevertheless essential for the fabrication of
complex polymeric architectures, such as block copolymers,11
multiblock copolymers, graft copolymers and star-shaped polymers.12
In principle, there are two distinct routes to introduce a func-
tional group via the chain transfer agent (CTA), either at the
The polymer community is continuously seeking for advanced
materials that fulfill high demands in a range of applications.
State-of-the-art methodology, as the conjunction of controlled
radical polymerization techniques (CRP)1 and postpolymeriza-
tion modifications, has enabled the synthesis of telechelic
polymers2 with precisely located functional groups at the poly-
mer chain ends. Besides the nitroxide-mediated polymerization
(NMP)3 and atom transfer radical polymerization (ATRP),4,5
the development of the reversible additionꢀfragmentation chain
transfer (RAFT)6,7 controlled polymerization technique has
enabled the preparation of a broad range of well-defined poly-
mers, thanks to its exceptional versatility and its tolerance for
diverse functional groups.8,9 The RAFT process allows for the
Received: April 6, 2011
Revised:
June 9, 2011
Published: June 22, 2011
r
2011 American Chemical Society
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R-chain end through the functional CTA itself,13ꢀ17 or at the ω-
chain end by chemical treatment of a trithiocarbonate RAFT
agent, typically with an amine,18,19 leading to a thiol-functional
polymer. Despite unavoidable side reactions during the aminolysis,20
we have lately utilized this route to obtain thiol terminated
polymers.21
dendrimers in a solvent-free system,44 while Schlaad and co-
workers have modified poly[2-(3-butenyl)-2-oxazoline] using a
thio-click approach.45 A recent review of Hoyle and Bowman
highlights both the mechanism and recent advances in applica-
tions of the radical thiolꢀene reaction.31
In realizing the great potential of thiolꢀene chemistry in
combination with the RAFT process, our research has been
focusing on the synthesis of R-norbornenyl functional polymers,
as it has been recognized that the norbornenyl (Nb) group has
the highest reactivity toward thiols in thiolꢀene reaction.30,46
There has already been growing interest in the study of norbor-
nenyl terminated macromonomers, due to the fact that the highly
ring-strained norbornene entity readily polymerizes in ring-opening
metathesis polymerization (ROMP).47,48 The unreactive char-
acter of the in-chain double bonds that are formed upon ROMP
originates from the neighboring cyclopentylene rings that are
preventing the acyclic double bonds of polynorbornene to
participate in transfer reactions.49 Taking advantage of these
specific features, norbornene-functionalized polymers have been
prepared using anionic polymerization and cationic ring-opening
polymerization as exemplified by the work of Heroquez et al.50,51
Unfortunately, these methods require strict laboratory proce-
dures and quantitative end-group fidelity is not always assured,
especially when targeting higher molecular weights. On the other
hand, the pioneering studies on CRP techniques that have been
done for the last decades, show clear advantages over both anionic
and cationic polymerizations. However, the preparation of norbor-
nenyl semitelechelic polymers via CRP with a high end group
fidelity still remains a difficult task. For instance, Cheng et al.52
reported on the synthesis of a norbornene-functionalized ATRP
initiator for the preparation of R-norbornenyl macromonomers.
When styrene (St) was used as the monomer, the polymerization
was well controlled with narrow monomodal molecular weight
distributions and quantitative norbornenyl end-group functionality.
In contrast, the norbornene group exhibited competitive reacti-
vity during the polymerizations of methyl acrylate (MA) and
tert-butyl acrylate (tBA). Similar to this functional initiator ap-
proach, there are several contributions reporting on the synthesis
of norbornenyl-functionalized RAFT agents via esterification,
employing N, N0-dicyclohexylcarbodimide (DCC) and 4-N,
N0-(dimethylamino)pyridine (DMAP). For example, Cheng
et al.53 prepared an exo-norbornene-functionalized RAFT agent
by esterification of a norbornene-functionalized alcohol with an
acid-functionalized RAFT agent. This compound has been used
for the one-pot tandem brush synthesis by ROMP of an
exo-norbornene functionalized RAFT agent, followed by RAFT
copolymerization of styrene and maleic anhydride (MAn),
mediated by a polyfunctional RAFT agent that resulted from
the first reaction step. In another example, the same research
group demonstrated the use of ROMP-active RAFT CTA,
containing both a norbornene and a trithiocarbonate function-
ality, for the synthesis of poly(tert-butyl acrylate) (PtBA) to
afford brush architectures via the ROMP of terminal norbornenyl
groups of PtBA.54 Recently, this approach was extended to
heterografted amphiphilic diblock molecular brushes employing
the same RAFT agentto obtain bothPtBAand poly(styrene) (PS)
macromonomers as precursors for the brushes.55 In the same
manner, Patton et al.56 modified 4-cyano-4-((thiobenzoyl)sulfanyl)-
pentanoic acid (CVADTB) to act as a CTA in the synthesis of
R-functionalized norbornenyl, vinyl, and cinnamyl macromono-
mers, obtaining near-quantitative end-group fidelity. While po-
lymerization of St and methyl methacrylate (MMA) monomers
In this study we focus on the polymerization using specifically
designed functional RAFT agents, resulting in a variety of
semitelechelic polymers with unique functional groups at the
R-terminus, which allow for thiolꢀene reactions in a second
stage. The concept of postpolymerization modification extends
the range of accessible functional polymers and copolymers that
are potentially applicable in both academic and industrial envir-
onment. Still, efficiency, robustness, and orthogonality, which are
of paramount importance for the successful altering of physico-
chemical properties for further applications of these systems, may
be improved. In recent years, a large number of studies has been
devoted to the Huisgen Cu-catalyzed azide/alkyne click
(CuAAC) reaction,22 demonstrating the power of postpolymer-
ization modification when combined with CRP techniques.23ꢀ27
However, the inevitable use of the toxic copper(I) catalyst
represents its major obstacle to meet strict biological require-
ments. In order to avoid the use of a copper catalyst, a set of
alternative click strategies has been offered.28 Mansfeld et al.29
have recently reviewed clickable initiators, monomers and poly-
mers, suggesting the polymer chemists what is a suitable combi-
nation of CRP and “click” approach for a desired polymeric
architecture. In that context, thiolꢀene reaction has emerged as
an extremely powerful synthetic tool,30,31 mainly because of its
high efficiency, robustness, oxygen tolerance, and commercial
availability of thiol and ene-containing compounds. The affinity
of thiols toward unactivated alkenes has been known for a long
time,32 especially in the vulcanization of rubbers.33 The radical
thiolꢀene step-growth polymerization mechanism was first
proposed in 193834 and was extensively studied over the last
century. Model kinetic investigations of thiolꢀene photopoly-
merization35,36 revealed that propagation to chain transfer ratio
(kp/kct) has a dramatic impact on the reaction kinetics and
significantly depends on the nature of the ene functional group. It
has been postulated that kp and kct, and therefore the reaction
rate, are correlated to the electron density of the carbonꢀcarbon
double bond and the intermediate carbon radical stability, re-
spectively,35 whereas the chain transfer step is shown to be the
rate limiting step.36
It is important to note that a number of potential side reactions
has to be considered, such as thiylꢀthiyl radical coupling, which
leads to disulfide formation, and head to head coupling of the
carbon centered radicals. Those side reactions lead to limitations
of the radical thiolꢀene chemistry, which we reported in a pre-
vious contribution.21 To mention the benefits, thiolꢀene reac-
tions require no transition metal catalyst and proceed with
exceptionally high yields, preferably under UV light. In addition,
the reaction could be thermally initiated, however with lower
efficiency.37 The thiolꢀene approach seems attractive as the
introduction of terminal thiol groups is straightforward18,19 and,
in some cases, the reaction could be performed in the presence of
oxygen,38 even without photoinitiator,39,40 and even under the
sunlight instead of UV light.41 Indeed, it was Schlaad and co-
workers who did initial efforts to extend the applicability of
radical thiolꢀene chemistry as a modular chemical tool for
advanced macromolecular designs.23,42,43 For example, Killops
et al. have employed thiolꢀene chemistry for the preparation of
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yielded well-defined macromonomers, monomers such as MA
manifested a broader polydispersity, showing a lack of inertness
in the free radical polymerization process. In all cases, the
necessity of suppressing the reactivity of the norbornenyl func-
tional group during the RAFT process had to be fulfilled, there-
fore lower temperatures were typically applied and monomer con-
versions were maintained low. Finally, norbornenyl-functionalized
monomers have been investigated in the preparation of multi-
functional polymer architectures for their application as smart and
advanced materials.57ꢀ59
In this work, we introduce a new family of Nb based RAFT
agents, prepared in a straightforward way, for the synthesis of a
wide range of norbornene-functionalized R-semitelechelics,
which provides a basis upon which advanced architectures may
be built, ideally via thiolꢀene chemistry. The synthetic platform
presented here allows for the design of diverse CTAs, and could
be readily extended to other functional group of interest, in a
fashion that considerably differs from literature examples given so
far.52ꢀ56,60 Another feature associated with our synthetic ap-
proach is the odor-free character of the norbornene CTAs, and
their high stability under daylight and common atmospheric
conditions (see Supporting Information). As the CTAs’ success
in mediating radical polymerization is crucial, we studied their
applicability for a variety of vinyl monomers. We investigated the
preparation of R-norbornene polymers with the aim to develop
the most reactive thiolꢀene system, consisting of thiol and
norbornene functional groups. The highly reactive macromono-
mers can serve as potential building block precursors for the
construction of functional and conjugated polymers, biopoly-
mers and more complex advanced macromolecular materials. To
demonstrate the highly reactive nature of the macromonomers,
their reactivity was compared to similar allyl-containing reactive
species in the thiolꢀene reaction.
equipped with two Plgel 5 μm MIXED-D columns 40 °C. Polystyrene
standards were used for calibration and THF as eluent at a flow rate of
1 mL/min. Samples were injected using a PL AS RT autosampler.
Mass spectra were obtained by ElectroSpray Ionization (ESIꢀMS)
using an Agilent 1100 series VL single-quad ESꢀMSD mass detector.
Compounds 5, NbꢀTTC, NbꢀDTB, NbꢀXan, and AllylꢀTTC tend
to fragment readily upon ionization. The most characteristic peaks (m/z)
were given and assigned; the relative intensities were determined, by
comparing the height of the corresponding peak to the most intense
(100%) peak.
Infrared spectra were obtained on a Perkin-Elmer 1600 series infrared
spectrophotometer using potassium bromide (KBr) plates.
Ultraviolet (UV) light irradiation was performed with a 900 W VL
400-L UV lamp, which emits at 365 nm (intensity ca. 16 mW cmꢀ2).
Synthesis of exo-5-({[4-(Bromomethyl)benzyl]oxy}methyl)-
bicyclo[2.2.1]hept-2-ene (4). Compound 4 (Scheme 2) was pre-
pared by a reported procedure,63 starting from distilled (()-exo-5-
norbornene-2-methanol.61 The synthesis was repeated on 5 g scale and
compound 4 was isolated after column chromatography with 53% yield.
Spectroscopic data (1H NMR, 13C NMR, ESIꢀMS) of purified 4 matched
the reported data.
Synthesis of 4-({[2-exo]-Bicyclo[2.2.1]hept-5-en-2ylmethoxy}-
methyl)benzyl Butyl Carbonotrithioate (Norbornenyl-
Functionalized CTA, Trithiocarbonate, NbꢀTTC). A solution
of benzylic bromide (4) (1.47 g, 4.785 mmol) in anhydrous THF
(10 mL) was transferred (via cannulation) to a mixture of sodium
1-butanethiolate (805 mg, 7.177 mmol) and CS2 (432 μL, 7.177 mmol)
in anhydrous THF (15 mL). The resulting yellow mixture was stirred
overnight at room temperature. The reaction was quenched with brine
(100 mL) and the aqueous layer extracted with diethyl ether (3 ꢁ 150 mL).
The combined organic extracts were dried (MgSO4), filtered and
evaporated in vacuo. The crude norbornenyl RAFT CTA (NbꢀTTC)
was purified by column chromatography (n-hexane/CH2Cl2: 8/2) and
isolated as a yellow oil in 98% (1.846 g, 4.702 mmol) yield.
C21H28OS3 (392.64 g/mol).
1H NMR (CDCl3) δ (ppm): 7.34ꢀ7.28 (m, 4H), 6.10 (dd, 1H, 5.6, 3.0
Hz), 6.05 (dd, 1H, 5.6, 2.8 Hz), 4.61 (s, 2H), 4.50 (s, 2H), 3.52 (dd, 1H, 9.2,
6.2 Hz), 3.37 (m, 3H), 2.79 (m, 2H), 1.77ꢀ1.64 (m, 3H), 1.43 (m, 2H),
1.34ꢀ1.21 (m, 3H), 1.11 (app dt, 1H, 11.6, 3.9 Hz), 0.94 (t, 3H, 7.3 Hz).
13C NMR (CDCl3) δ (ppm): 224.0, 138.6, 136.9, 136.8, 134.5, 129.5,
128.1, 75.3, 72.9, 45.2, 44.0, 41.8, 41.3, 39.1, 37.0, 30.3, 30.0, 22.3, 13.8.
ESIꢀMS (m/z): 393 (38%) [M + H+], 269 (100%).
’ EXPERIMENTAL SECTION
Materials. R,R0-Dibromo-p-xylene (97%), carbon disulfide (g99.9%),
sodium hydride (95%), sodium 1-butanethiolate (g95%), potassium
ethyl xanthogenate (96%), 2,20-azobis(isobutyronitrile) (AIBN), phe-
nylmagnesium bromide (3.0 M in diethyl ether), 2,2-dimethoxy-2-
phenylacetophenone (DMPA) (99%), 1-dodecanethiol (g98%), ben-
zyl mercaptan (99%) and 3-mercaptopropionic acid (g99%) were
purchased from Sigma-Aldrich and used as received. Vinyl acetate
(VAc) (99+ %, Sigma-Aldrich) was passed through a column of basic
alumina to remove the radical inhibitor. Styrene (St) (99%, extra pure,
Acros Organics) was passed through a column of basic alumina to
remove the radical inhibitor. 2,20-Azobis(isobutyronitrile) (AIBN) (Sigma-
Aldrich) was recrystallized twice from methanol. Allyl alcohol (>98%) was
purchased from Merck and distilled prior to use. (()-exo-5-Norbornene-2-
methanol was synthesized following a literature procedure61 and distilled
prior to use. THF was freshly distilled over sodium/benzophenone.
1-ethoxyethyl acrylate (EEA) was prepared following the procedure of
Van Camp et al.62
Synthesis of O-Ethyl-S-4-({[2-exo]-Bicyclo[2.2.1]hept-5-
en-2ylmethoxy}methyl)benzyl Carbonodithioate (Norbornenyl-
Functionalized CTA, Xanthate, NbꢀXan). A solution of benzylic
bromide (4) (1.0 g, 3.255 mmol) in anhydrous THF (10 mL) was
transferred (via cannulation) to a mixture of potassium ethyl xantho-
genate (782 mg, 4.882 mmol) in anhydrous THF (15 mL). The
resulting turbid mixture was stirred overnight at room temperature.
The reaction was quenched with brine (100 mL) and the aqueous layer
extracted with diethyl ether (3 ꢁ 150 mL). The combined organic
extracts were dried (MgSO4), filtered and evaporated in vacuo. The
crude norbornenyl RAFT CTA (NbꢀXan) was purified by column
chromatography (n-hexane/CH2Cl2 = 8/2) and isolated as a yellowish
oil in quantitative yield (>99%) (1.13 g, 3.242 mmol).
Characterization. Nuclear magnetic resonance (1H-and 13C NMR)
spectra were recorded at 300 or 500 MHz in CDCl3 solution at room
temperature on a Bruker Avance 300 or Bruker DRX500 spectrometer,
respectively. Chemical shifts are presented in parts per million (δ)
C19H24O2S2 (348.52 g/mol).
1H NMR (CDCl3) δ(ppm): 7.34ꢀ7.28(m, 4H), 6.10 (dd, 1H, 5.6, 3.0
Hz), 6.05 (dd, 1H, 5.6, 2.8 Hz), 4.66 (q, 2H, 7.1 Hz), 4.50 (s, 2H), 4.36
(s, 2H), 3.52 (dd, 1H, 9.2, 6.3 Hz), 3.37 (app t, 1H, 9.0 Hz), 2.79 (m, 2H),
1.72 (m, 1H), 1.42 (t, 3H, 7.1 Hz), 1.35ꢀ1.18 (m, 3H), 1.11 (app dt, 1H,
11.6, 3.9 Hz).
1
relative to CHCl3 (7.26 ppm in H- and 77.2 ppm in 13C NMR) as
internal standard. Coupling constants (J) in 1H NMR are given in Hz.
The resonance multiplicities are described as s (singlet), d (doublet),
app t (apparent triplet), q (quartet) or m (multiplet).
13C NMR (CDCl3) δ (ppm): 214.2, 138.4, 136.9, 136.8, 135.1, 129.3,
128.1, 75.3, 72.9, 70.2, 45.2, 44.0, 41.8, 40.4, 39.1, 30.0, 14.0.
ESIꢀMS (m/z): 349 (27%) [M + H+], 225 (100%).
Size Exclusion Chromatography (SEC) analyses were performed on a
Varian PLGPC50plus instrument, using a refractive index detector,
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Table 1. Summary of the Optimized Reaction Conditions and Results of Polymerization of St, MA, and EEA Mediated by
NbꢀTTC
entry
M
[M]0/[CTA]0/[AIBN]0
solvent, vol %
T, °C
time, h
convn,a %
Mnexp,b g/mol
PDIb
F. degree,c %
1
St
200/1/0.1
200/1/0.1
200/1/0.1
200/1/0.1
200/1/0.1
200/1/0.1
200/1/0.1
200/1/0.1
200/1/0.1
400/1/0.1
600/1/0.1
200/1/0.1
toluene, 25
toluene, 25
toluene, 25
toluene, 50
toluene, 25
toluene, 25
toluene, 25
bulk
60
70
80
70
70
70
70
70
70
65
65
62
6
6
16
19
24
16
16
24
40
24
47
31
75
69
3100
4000
4400
3300
3700
5200
6800
6100
8500
10500
34600
15800
1.23
1.24
1.27
1.28
1.23
1.24
1.27
1.25
1.25
1.12
1.31
1.31
>90
>90
61
2
St
3
St
6
4
St
6
86
5
St
4
>90
>90
73
6
St
8
7
St
24
8
8
St
>90
>90
86
9
St
bulk
18
6
10
11
12
MA
MA
EEA
toluene, 25
toluene, 25
toluene, 25
12
77
12
68
a Calculated from 1H NMR. b SEC, calibrated with PS standards, THF as eluent. c Calculated from 1H NMR and SEC.
Synthesis of 4-({[2-exo]-Bicyclo[2.2.1]hept-5-en-2ylmethoxy}-
methyl)benzyl Dithiobenzoate (Norbornenyl-Functionalized
CTA, Dithiobenzoate, NbꢀDTB). A solution of benzylic bromide
(4) (0.5 g, 1.627 mmol) in anhydrous THF (5 mL) was transferred (via
cannulation) to a red solution of phenylmagnesium bromide (0.65 mL,
1.953 mmol, 3.0 M in ether) and CS2 (117 μL, 1.953 mmol) in anhydrous
THF (10 mL) at 0 °C. The resulting mixture was stirred overnight
(0 °Cꢀrt). The reaction was quenched with brine (100 mL) and the
aqueous layer extracted with diethyl ether (3 ꢁ 150 mL). The combined
organic extracts were dried (MgSO4), filtered and evaporated in vacuo.
The crude norbornenyl RAFT CTA (NbꢀDTB) was purified by column
chromatography (n-hexane/CH2Cl2: 95/5) and isolated as a pink oil in
90% yield (562 mg, 1.477 mmol).
Synthesis of 4-({Allyloxy}methyl)benzyl Butyl Carbono-
trithioate (Allyl-Functionalized CTA, Trithiocarbonate, Allylꢀ
TTC). A solution of the benzylic bromide (5) (1.0 g, 4.147 mmol) in
anhydrous THF (10mL) was transferred(via cannulation) to a mixture of
sodium 1-butanethiolate (700 mg, 6.221 mmol) and CS2 (374 μL, 6.221
mmol) in anhydrous THF (15 mL). The resulting yellow mixture is
stirred for 4 h at room temperature. The reaction was quenched with
brine (100 mL) and the aqueous layer extracted with diethyl ether (3 ꢁ
100 mL). The combined organic extracts were dried (MgSO4), filtered
and evaporated in vacuo. The crude allyl RAFT CTA (AllylꢀTTC) was
purified by column chromatography (n-hexane/CH2Cl2: 7/3 to 1/1) and
isolated as a brown oil in 97% (1.32 g, 4.040 mmol) yield.
C16H22OS3 (326.54 g/mol).
C23H24OS2 (380.57 g/mol).
1H NMR (CDCl3) δ (ppm): 7.34ꢀ7.28 (m, 4H), 5.95 (dddd, 1H,
17.2, 10.4, 5.6, 5.5 Hz), 5.31 (ddd, 1H, 17.2, 3.3, 1.6 Hz), 5.21 (ddd, 1H,
10.4, 2.9, 1.3 Hz), 4.60 (s, 2H), 4.50 (s, 2H), 4.02 (app dt, 2H, 5.6, 1.4 Hz),
3.38 (app t, 2H, 7.4 Hz), 1.68 (m, 2H), 1.43 (m, 2H), 0.94 (t, 3H, 7.3 Hz).
13C NMR (CDCl3) δ (ppm): 224.0, 138.2, 134.9, 134.6, 129.5, 128.2,
117.4, 71.9, 71.4, 41.3, 37.0, 30.2, 22.3, 13.8.
1H NMR (CDCl3) δ (ppm): 8.00 (m, 2H); 7.52 (m, 1H), 7.40ꢀ7.31
(m, 6H), 6.11 (dd, 1H, 5.6, 3.0 Hz), 6.06 (dd, 1H, 5.6, 2.8 Hz), 4.60
(s, 2H), 4.52 (s, 2H), 3.52 (dd, 1H, 9.2, 6.2 Hz), 3.38 (app t, 1H, 9.0 Hz),
2.79 (m, 2H), 1.74 (m, 1H), 1.34ꢀ1.21 (m, 3H), 1.11 (app dt, 1H, 11.6,
3.9 Hz).
13C NMR (CDCl3) δ (ppm): 227.9, 145.0, 138.6, 136.9, 136.8, 134.4,
132.6, 129.6, 129.3, 128.2, 127.1, 75.4, 72.9, 45.2, 44.0, 42.3, 41.8,
39.1, 30.0.
ESIꢀMS (m/z): 349 (<1%) [M + Na+], 327 (1%) [M + H+], 269
(100%).
General Polymerization Procedures. All polymerizations were
performed in a Schlenk tube and AIBN was employed as the thermal
initiator. A typical polymerization procedure is as follows (Scheme 3):
monomer, norbornenyl CTA, initiator, and solvent ([M]0/[CTA]0/
[AIBN]0 = 200/1/0.1) were placed in a Schlenk tube, which was
degassed by three freezeꢀpumpꢀthaw cycles, backfilled with nitrogen,
sealed, and heated in an oil bath at the indicated temperature. The
applied reaction time ranged from 2 to 48 h, depending on the targeted
molecular weight and research purpose. The concentrations and reac-
tion conditions for each specific reaction are given in Tables 1, 2 and 3.
All reaction mixtures were quenched in liquid nitrogen. The polymer-
ization kinetics using the various NbꢀCTA were monitored by 1H NMR
and SEC. For each single reaction, at specific time intervals during the
polymerization, small aliquots were withdrawn from the polymerization
solution and analyzed by 1H NMR spectroscopy for the determination
of monomer conversions and by SEC for the determination of the
molecular weights and polydispersities (PDI) of the resulting polymers.
The purified polymers were obtained by repeated precipitation in
10-fold excess of corresponding nonsolvent (cold methanol for PS,
50/50 cold mixture of methanol and water for PMA/PEEA, cold hexane
for PVAc). Alternatively, PEEA and PVAc were purified by removing
monomer in vacuo. Polymers were collected either by decantation or
filtration and dried at least overnight in vacuo.
ESIꢀMS (m/z): 663 (40%), 381 (49%) [M + H+], 257 (100%).
Synthesis of 4-({Allyloxy}methyl)benzyl Bromide (5). An
ice-cooled solution of freshly distilled allylalcohol (840 μL, 12.37 mmol)
in anhydrous THF (50 mL) was treated with NaH (445 mg, 18.56
mmol) and stirred for 1 h at 0 °C. A solution of R,R0-dibromo-p-xylene
(1, 4.0 g, 15.15 mmol) in anhydrous THF (35 mL) was added to the
turbid mixture via cannulation and the resulting mixture was heated at
80 °C for 2 h. The resulting bright yellow reaction mixture was cooled to
room temperature and quenched by adding a saturated aqueous NH4Cl
solution (100 mL). The layers were separated and the aqueous layer was
extracted with diethyl ether (3 ꢁ 250 mL). The combined organic
extracts were dried (MgSO4), filtered and evaporated in vacuo. The
crude benzylic bromide (5) was purified by column chromatogra
phy (n-hexane/CH2Cl2: 6/4) and isolated as a colorless oil in 53%
(1.585 g, 6.573 mmol) yield.
C11H13BrO (241.12 g/mol).
1H NMR (CDCl3) δ (ppm): 7.39ꢀ7.31 (m, 4H), 5.96 (dddd, 1H,
17.3, 10.4, 5.6, 5.5 Hz), 5.31 (ddd, 1H, 17.3, 3.3, 1.7 Hz), 5.21 (ddd, 1H,
10.4, 2.9, 1.4 Hz), 4.52 (s, 2H), 4.50 (s, 2H), 4.04 (app dt, 2H, 5.6, 1.4 Hz).
13C NMR (CDCl3) δ (ppm): 139.0, 137.3, 134.8, 129.3, 128.2, 117.4,
71.8, 71.5, 33.5.
ESIꢀMS (m/z): 161 (100%) [M ꢀ Br]+.
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General Procedure for ThiolꢀEne Reaction. A typical proce-
containing CTAs.56 Likewise, Wooley and co-workers converted
commercially available S-1-dodecyl-S0-(R,R0-dimethyl-R00-acetic
acid)trithiocarbonate (DDMAT) through esterification to the
desired CTA.53 The presented approach enabled us to introduce
on one hand a variety of double bond containing moieties in the
R-group, and on the other hand several Z-groups, thus resulting
in different types of CTAs. Indeed, the corresponding trithio-
carbonate, xanthate and dithiobenzoate are readily available
through a similar procedure, which emphasizes the versatility
of this methodology. Using these CTAs, a wide range of mono-
mers (e.g., styrenes, acrylates, vinylacetate, ...) can be polymer-
ized in a controlled fashion. Moreover, the newly designed CTAs
carry a double bond, which is linked through a nonhydrolyzable
ether bond, in contrast to the ester linkage used by others.53,56
The norbornene benzylic bromide precursor (4, Scheme 2)
was prepared by monosubstitution of R,R0-dibromo-p-xylene63
(1, Scheme 1) with the sodium anion of (()-exo-5-norbornene-
2-methanol.61 The exo-adduct was used as the steric hindrance
dure is as follows (Table 4, entry 1): Nb-containing polymer (PS, 0.08 g,
1.6 ꢁ 10ꢀ5 mol, Mn = 5000 g molꢀ1, PDI = 1.27) and thiol-containing
3
compound (dodecanethiol, benzyl mercaptan or 2-mercaptopropionic
acid), and 0.2 equiv of photoinitiator 2,2-dimethoxy-2-phenylacetophe-
none (DMPA, 0.8 mg, 3.2 ꢁ 10ꢀ6 mol) were placed in a Schlenk tube and
dissolved in minimal amounts of THF (0.9 mL) required to dissolve all
components. The tube was sealed and the reaction mixture was degassed
with three freezeꢀpumpꢀthaw cycles, backfilled with nitrogen, and placed
under an irradiation source. The flask was irradiated with a 365 nm UV lamp,
and was positioned at 45° toward the irradiation source, to ensure equal
irradiation over the whole reacting mixture (distance between irradiation
source and the flask ca. 20 cm). Irradiation time was typically 15 min except
otherwise mentioned. The resulting functional polymers were precipitated
three times in corresponding cold nonsolvent as stated above.
’ RESULTS AND DISCUSSION
In the first part of the contribution, an universal synthetic
platform for the preparation of various Nb- and allyl-containing
CTAs (trithiocarbonate, dithiobenzoate, and xanthate) is pre-
sented. In a second part of our research, the polymerization of a
range of vinyl and acrylic monomers mediated by the new CTAs
is examined. For the investigated conditions, the interference of
the Nb functional group during the radical process was studied,
as this strongly affects the resulting end group fidelity. In the last
section, we focused on the thiolꢀene modifications leading to
polymers with altered chain-end structures. The major interest of
the current study is to modify the Nb polymer terminus, which is
expected to undergo the most efficient thiol addition.
Synthesis of the Functional Chain-Transfer Agents. The
design of the Nb-containing chain transfer agents (CTAs) was
based on the desymmetrization of R,R0-dibromo-p-xyleꢀne (1,
Scheme 1) by monosubstitution with an alkoxide anion ( OR0)
and subsequent replacement of the residual bromine atom in
the benzylic bromide (2, Scheme 1) to create the RAFT CTA
(3, Scheme 1). The xylene moiety is the central part of the R (free
radical leaving) group of the resulting CTA (3, Scheme 1). So far,
the synthesis of norbornenyl-CTAs merely consisted of decora-
tion of known RAFT agents. Advincula and co-workers used
4-cyano-4-((thiobenzoyl)sulfanyl)pentanoic acid (CVADTB) as
a starting material for the synthesis of several double bond
Table 4. Summary of the Reaction Conditions and Results for
the ThiolꢀEne Post-Polymerization Modification of PSa
PSꢀNb,
g/mol
thiol,
irradiation
convn,c
%
entryb
thiol
equiv
time, min
1
2
3
4
5
6
DdSH
DdSH
DdSH
MPA
BSH
5000
5000
5000
6000
6000
6000
1
5
5
1
1
5
15
15
10
15
15
15
70
>90
>90
>90
45
BSH
>90
PSꢀallyl,
g/mol
thiol,
equiv
irradiation
time, min
convn,c
%
entryb
thiol
7
8
9
DdSH
MPA
BSH
4200
4200
4200
1
1
1
15
15
15
20
30
15
a Abbreviations: DdSH, dodecanethiol; MPA, 2-mercaptopropionic
acid; BSH, benzyl mercaptan. b All reactions were performed in THF
as a solvent, DMPA photoinitiator, under λ = 365 nm. c Conversion yields
percentage calculated from the disappearance of Nb peaks by 1H NMR.
Table 2. Summary of the Optimized Reaction Conditions
and Results of Polymerization of St Mediated by
NbꢀDithiobenzoate and AllylꢀTTC
Scheme 1. Structural Design and General Reaction Scheme
of Double-Bond-Containing RAFT CTAsa
entrya
CTA
time, h convn,b % Mnexp,c g/mol PDIc F. degree,d %
1
2
3
NbꢀDTB
AllylꢀTTC
AllylꢀTTC
8
6
4
25
19
11
4800
4100
3000
1.20
1.28
1.29
>90
>90
90
a Reaction conditions: [M]0/[CTA]0/[AIBN]0 = 200/1/0.1; 25 vol %
toluene; 70 °C. b Calculated from H NMR. c SEC, calibrated with PS
a R0 = norbornene or other double bond containing moiety; Z = O---,
S---, Ph.
1
standards, THF as eluent. d Calculated from 1H NMR and SEC.
Table 3. Summary of the Optimized Reaction Conditions and Results for Polymerization of VAc in Bulk, Mediated by NbꢀXan
entry
[M]0/[CTA]0/[AIBN]0
T, °C
time, h
convn,a %
Mnexp,b g/mol
PDIb
F. degree,c %
1
2
3
200/1/0.5
200/1/0.5
200/1/0.5
60
70
70
26
3.5
4
66
34
58
17 000
10 300
17 500
1.48
1.27
1.46
<50
>90
<50
a Calculated from 1H NMR. b SEC, calibrated with PS standards, THF as eluent. c Calculated from 1H NMR and SEC.
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Scheme 2. Synthesis of Norbornenylꢀ and AllylꢀRAFT
(MA), and 1-ethoxyethyl acrylate (EEA), leading to semitele-
chelic polymers bearing a Nb group at the R terminus. EEA was
chosen because the corresponding poly(1-ethoxyethyl acrylate)
(PEEA) can be converted to poly(acrylic acid) (PAA) by a
simple heating step at 80 °C.62 The radical (co)polymerization
reactivity of Nb species relative to St and acrylate based mono-
mers was particularly important for the selection of appropriate
reaction conditions. Theoretically, polymerization of these mono-
mers mediated by NbꢀTTC could be considered as the copo-
lymerization of two distinct vinyl monomers (e.g., Nb based
CTA and St, MA or EEA monomer, respectively), where r1 and r2
are the ratios of the rate constants of the different pro-
pagation reactions for any monomer pair. Therefore, the radical
copolymerization reactivity ratios (r1 and r2) were calculated
based on Alfrey and Price equations:65
CTAsa
r1 ¼ ðQ1=Q2Þ exp½ ꢀ e1ðe1 ꢀ e2Þꢂ
ð1Þ
r2 ¼ ðQ2=Q1Þ exp½ ꢀ e2ðe2 ꢀ e1Þꢂ
ð2Þ
where Q is a measure of the reactivity, while e stands for the
monomer polarity. Low homopolymerization rates for different
norbornene derivatives were previously reported.52,58,66 To
estimate the reactivity of our Nb based CTAs, we employed Q
and e parameters of norbornadiene (Q = 0.051, e = ꢀ1.48).67
Taking into account Q and e values for St (Q = 1, e = ꢀ0.80), MA
and its analogue EEA (Q = 0.45, e = 0.64), reactivity ratios r1/r2
for the Nb - St and Nb ꢀ MA/EEA pairs were 1820 and 460,
respectively, indicating an extremely low tendency of the Nb
group to (co)polymerize with regard to the selected monomers.
In all polymerization reactions, the concentration of Nb species
was maintained low, and conversions of St and acrylates were
kept below 50% and 30%, respectively, to suppress side reactions
with the Nb functionality during the polymerization reactions.
Furthermore, we have investigated the influence of monomer-to-
CTA ratio and temperature on the polymerization kinetics,
ensuring that the Nb species remain intact during the entire
radical polymerization process.
Table 1 summarizes the optimized reaction conditions and
results of the polymerization of St, MA and EEA mediated by
NbꢀTTC. The effect of different reaction parameters such as
temperature, dilution, monomer to CTA ratio and conversion
was investigated in order to establish the optimal conditions for
St homopolymerization (Scheme 3). For each specific tempera-
ture (entries 1, 2 and 3), the impact of various amounts of toluene
as a solvent (e.g., bulk, 25 and 50 vol %), CTA concentrations
and conversions have been investigated. The polymerization was
thermally initiated employing 0.1 equiv of AIBN, following
standard literature conditions. We found that the occurrence of
side reactions is directly related to the temperature as the key
parameter, having significant influence on the conversion. At
60 °C, St polymerization proceeded slowly (Table 1, entry 1)
with the maintained high end group fidelity, as a result of the low
conversion. The temperature increase up to 70 °C (Table 1,
entry 2) caused an increase in the reaction rate, still with a minor
end group loss that is comparable to the case of a reaction
temperature of 60 °C. Further temperature increase, i.e., 80 °C,
resulted in faster reaction kinetics, but also in a significant loss of
the Nb end functional group. Such a temperature trend was
perceived for either bulk, 25 vol % solution and 50 vol % solution
conditions (Table 1, entry 4). A high end group fidelity was also
retained during the bulk polymerization at 70 °C (Table 1,
a Reaction conditions: (A) exo-5-norbornene-2-methanol, NaH, THF,
overnight, 80°C; (B) CS2, sodium 1-butanethiolate, THF, overnight,
room temperature; (C) potassium ethyl xanthogenate, THF, overnight,
room temperature; (D) allyl alcohol, NaH, THF, 2 h, 80°C; (E) CS2,
sodium 1-butanethiolate, 4 h, room temperature. Presented yields are
those of the purified compounds.
around the carbonꢀcarbon double bond is less than in the case of
the endo-compound,52 enabling an easier approach of reactants
during the postpolymerization modification (e.g., thiyl radicals in
thiolꢀene chemistry). The trithiocarbonate NbꢀTTC was
synthesized by overnight treatment of the precursor with an ex-
cess of CS2 and sodium 1-butanethiolate. The choice of the
Z group in CTA NbꢀTTC was supported by the fact that an
analogous compound, benzyl butyl trithiocarbonate, was able to
mediate the controlled radical polymerization of butyl acrylate/
styrene AB and ABA blocks.64 Substitution of the benzylic
bromine atom in compound 4 with the ethyl xanthogenate
anion, using similar reactions conditions, provided the xanthate
NbꢀXan in quantitative yield (Scheme 2). The synthesis of the
corresponding dithiobenzoate NbꢀDTB was more challenging
as the highly reactive Grignard reagent (phenylmagnesium
bromide), which is used to generate the dithiobenzoic acid salt,
inhibits scaling up because of the complexity of the reaction
mixture, involving side products. Therefore, we decided to
perform a series of RAFT experiments with the trithiocarbonate
NbꢀTTC and xanthate NbꢀXan for which the synthesis scal-
ing up (g3 g CTA) is straightforward. The corresponding allyl-
functionalized RAFT CTA, trithiocarbonate AllylꢀTTC(Scheme2),
was synthesized employing the same reaction sequence, with an
identical overall yield, demonstrating the versatility and reliability
of the methodology, while serving in a later stage as a direct
comparison of the reactivity of both Nb and allyl species toward
thiolsin the thiolꢀene postpolymerization modification approach.
Synthesis and Characterization of the Norbornenyl (Nb)
Containing Semitelechelics. TrithiocarbonateꢀNb (NbꢀTTC).
The RAFT agent NbꢀTTC was verified for its capabilities of
mediating the homopolymerization of styrene (St), methyl acrylate
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Scheme 3. RAFT and ThiolꢀEne Synthetic Approach toward Functional Polymers: (a) RAFT Polymerization of St Mediated by
NbꢀTTC; (b) ThiolꢀEne Post-Polymerization Modification of Nb Containing PS
Figure 1. Polymerization of St using NbꢀTTC CTA, at 70 °C, in 25 vol % toluene and with 0.1 equiv AIBN as the radical source, St/NbꢀTTC = 200/1
(Table 1, entry 6): (a) first-order kinetic plot; (b) molecular weight and PDI evolution with monomer conversion; (c) detail of 500 MHz 1H NMR
(CDCl3) of Nb-containing PS; (d) functionalization degree as a function of time for the different polymerization temperatures (see Table 1, entries 1, 2 and 3).
entries 8 and 9), despite the relatively high radical concentration.
The high functionalization degree observed for bulk polymeri-
zation may be due to the relative reduction of the termination
rate constants in highly viscous media (Table 1, entries 8 and 9;
Figure S1, Supporting Information). Compromising between a
satisfactory reaction rate and high end-group fidelity, it was found
that 70 °C combined with either bulk or 25 vol % dilution are the
optimal conditions for the polymerization of St.
Figure 1a shows a linear first order kinetic plot, while a steady
increase of the molecular weight (MW) was observed and low
polydispersity indices (PDIs) were maintained with increasing
monomer conversion for entry 6, Table 1. SEC MW distributions
were essentially narrow and monomodal for the investigated
conversion range. The Nb functionality could be preserved to a
high level of ca. 90% (Table 1, entries 1, 2, 5, 6, 8 and 9; Figure 1)
under the optimal conditions. The end group functionalization
was calculated combining SEC and 500 MHz 1H NMR results,
considering the integration ratio of the corresponding benzene
ring region (6.3ꢀ7.26 ppm) and Nb doublet at 6.05 and 6.1
ppm (Figure 1c). Note that the functionalization degree will
never be quantitative as the RAFT mechanism results in a certain
amount of chains that will carry an AIBN adduct generated
during the initiation step. A detailed 1H NMR spectrum of Nb-
containing PS with integration values of corresponding end-
group signals is shown in Figure S2, Supporting Information.
For longer reaction times (Table 1, entry 7), a loss of Nb
functionality was observed (Figure 1d). The increased PDI
suggests that the Nb functionality was partially copolymerized
at higher monomer conversions, given that the monomer con-
centration is decreasing. Under such circumstances, a variety of
structures are formed along with the regular Nb-containing
polymer chains. For example, termination events cause longer-
chain linear polymers, while copolymerization at the Nb side
results in grafted-like and branched polymers. Such nondefined
structures lead to a disagreement between the experimental and
the theoretical Mn values. However, a straight MarkꢀHouwink
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Figure 2. (a) Polymerization of MA using NbꢀTTC CTA, at 65 °C, in 25 vol % toluene and with 0.1 equiv AIBN as the radical source, MA/NbꢀTTC =
600/1 (Table 1, entry 11): normalized SEC chromatograms showing shoulder formation at 30% conversion or higher (corresponds to 6 h reaction time).
(b) Polymerization of EEA using NbꢀTTC CTA, at 62 °C, in 25 vol % toluene and with 0.1 equiv AIBN as the radical source, EEA/NbꢀTTC = 200/1
(Table 1, entry 12): normalized SEC MW distribution for each aliquot recorder with the THF as eluent, showing shoulder formation at conversions higher
than 40%.
plot (Figure S3, Supporting Information) revealed no presence
of branched polymer species, indicating that neither transfer nor
termination reactions are occurring. Both H NMR and SEC
main signal correspond to the side reactions taking place at the
Nb site.
1
Next to MA, 1-ethoxyethyl acrylate (EEA) was polymerized
using the TTCꢀNb CTA. EEA was polymerized applying similar
conditions as for MA (Table 1, entry 12). Many of the key fea-
tures observed during the MA polymerization were also noticed
in the case of EEA. Likewise, SEC analysis revealed the appear-
ance of a shoulder at higher MW starting at ca. 40% conversion,
which was attributed to the Nb interference, which leads to ill-
defined structures, as discussed above in more detail (Figure 2b).
Although the evolution of the molecular weight vs conversion
was linear (Figure S6, Supporting Information), lack of control
was apparent from the increase in PDI values at conversions
higher than 40%. In addition, obtained experimental MWs are
significantly lower than theoretical MWs. Polymerization of EEA
in bulk at 60 °C resulted in a noncontrolled polymerization. In
contrast to the polymerization of St, bulk conditions lead to
significant propagation through the Nb group. This resulted in an
end group fidelity that was lower than 50% in comparison with
68% obtained in solution for PEEA, as evidenced by 500 MHz 1H
NMR analysis (Table 1, entry 12 and Figure S6c, Supporting
Information).
DithiobenzoateꢀNb (NbꢀDTB) and TrithiocarbonateꢀAllyl
(allylꢀTTC). In principle, the new synthetic CTA-platform allows
the introduction of other functions of interest instead of Nb. As
dithiobenzoates belong to the group of most active RAFT CTAs,
we have also synthesized dithiobenzoateꢀNb. Dithioester con-
taining RAFT agents have been used for the polymerization of
acrylic, methacrylic and styrenic monomers.8 Following the
optimal conditions that were found for the trithiocarboanteꢀNb
CTA, PS was prepared at 70 °C in 25 vol % toluene, while a low
monomer conversion (<30%) was targeted (Table 2, entry 1).
Well-defined PS was obtained (Figure S7, TTCꢀ), with an
excellent agreement between theoretical and experimental MWs,
low PDI (1.20) and essentially quantitative end group content
(>90%). In accordance with our findings stated above for NbꢀTTC
systems, either elevated reaction temperatures or high conver-
sions result in the loss of the Nb end group in the NbꢀDTB
approach.
showed that conversions higher than ca. 50% will cause side
reactions, concluding that conversion is a key parameter in
maintaining a high end group fidelity. Another reason for the
loss of Nb function with the extended reaction time might be the
transfer from the solvent, which causes radical addition to the Nb
double bond, while releasing the ring strain. However, change of
the solvent to dioxane resulted in a similar functionalization degree,
suggesting that transfer reactions from the aromatic solvent
(e.g., toluene) are not occurring and/or are not the reason for
the lacking presence of Nb moiety.
In conclusion, the performed experiments show that
TTCꢀNb CTA is capable of mediating the polymerization of
St in a well controlled manner, with preserved Nb functionality at
the R terminus.
In a similar way, to demonstrate the versatility of our approach,
the behavior of methyl acrylate (MA) and 1-ethoxyethyl acrylate
(EEA) in the RAFT process with TTCꢀNb CTA was studied.
The polymerization of MA was well-controlled under the con-
ditions highlighted in Table 1 (entries 10 and 11). For entry 10, a
well-controlled reaction with a constant radical concentration
was established, as shown by the linear increase of the number-
average molecular weights with increasing monomer conversion
1
(Figure S4, parts a and b, Supporting Information). H NMR
analysis revealed a high Nb content of 86% (Figure S4c,
Supporting Information). Since the radical reactivity parameters
of Nb and MA are not as distinct as in the case of St, copoly-
merization of MA and Nb species is known for many years.68,69
In particular, Advincula et al.56 and Wooley et al.52 noticed that
Nb containing initiation species significantly interfere during the
polymerization of acrylates, at conversions higher than 30%.
entry 11 (Table 1) basically confirms these statements, and,
although a high initial monomer to CTA ratio of 600/1 was em-
ployed, SEC analysis (Figure 2a) clearly shows shoulders appear-
ing at conversions higher than 30%, resulting in a dramatically
reduced functionalization degree (77%). The formation of mid-
chain radicals is likely to limit the end functionality to a significant
extent, introducing branching over the polymer backbone, as
judged by MarkꢀHouwink plots (Figure S5, Supporting In-
formation). Furthermore, shoulders appearing in SEC traces
with a peak molecular weights (Mp) that is twice the value of the
We have also prepared allyl-terminated CTA, which could serve
as a direct comparison of the reactivity of Nb and allyl species
toward thiols in radical thiolꢀene postmodification approach.
Similarly to the approach employed for Nb functionalized CTA,
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the Q and e values for the allyl group were estimated based on an
equivalent compound, in this case allyl acetate. In this way, the
estimated ratio of r1/r2 = 1940 for the St-allyl pair is even higher
than for the St-Nb pair, allowing the polymerization process to be
conducted with good selectivity between the two vinyl bonds.
Since the reactivity parameters are similar to those of the StꢀNb
system, we used the optimal RAFT conditions from previous
inquiries, resulting in a well-controlled polymerization process
with linear increase of MW with conversion (Figure S8, Support-
ing Information). Polymerization reaction yielded PS with high
allyl end group functionality, as depicted in Figure S8c, Support-
ing Information) from 1H NMR interpretation. Chain transfer to
polymer can take place through radical attack on the allyl double
bond, which can be explained by the fact that the allyl group is
unprotected, serving as the reactive center at the later stage of
polymerization process when the monomer is largely consumed.
Despite the relatively high PDI, no traces of higher MW pop-
ulation species were observed during SEC analysis, suggesting
that the polymerization proceeds in a controlled way (Table 2,
entries 2 and 3).
Figure 3. 500 MHz 1H NMR (CDCl3) spectrum detail of Nbꢀ
containing PVAc (Table 3, entry 2).
with high end group fidelity (Figure 3). However, higher monomer
conversions resulted in poor functionalization degree (Table 3,
entry 3).
XanthateꢀNb (NbꢀXan). Macromolecular design via the
interchange of xanthates (MADIX)70 follows the same mechan-
ism as RAFT and varies only in the choice of mediating agent, the
so-called xanthate CTA. Xanthate CTAs enable the control over
RAFT polymerizations of vinyl acetate (VAc), vinylpyrrolidone
(NVP), and related vinyl monomers where the propagating
radical is a relatively poor homolytic leaving group. Extending
our synthetic platform toward Nb based CTAs, NbꢀXan was
prepared (Scheme 2) and was subsequently used to mediate the
polymerization of VAc. As the preparation of well-defined PVAc
remains rather challenging, we have modified compound 4
(Scheme 2), in order to ensure successful polymerization of
VAc. Barner-Kowollik et al.71 studied the influence of different Z
groups on the polymerization of VAc and found that Z equal to
OCH2CH3 could lead to well-defined PVAc with PDI below 1.2.
According to our previous research,21 the polymerization of
VAc was conducted in bulk at two different temperatures (60 and
70 °C) employing different equivalents of AIBN as a thermal
radical initiator, and a targeted degree of polymerization (DP) of
200. In many cases, however, we observed an induction or
inhibition effect at the early stage of the polymerization, which
is typical for fast propagating monomers such as VAc, and is most
likely caused by the slow fragmentation of the intermediate
radical. It has also been reported that impurities present in a re-
acting solution may cause such a behavior.72 Moreover, increas-
ing the CTA concentration intensified the inhibition effect.
Initial polymerization reactions were attempted with mono-
mer to CTA ratio of 200, 0.1, and 0.2 equiv of AIBN at 60 °C but
yielded no polymer (not shown in Table 3). Significant increase
of AIBN up to 0.5 equiv allowed us to initiate polymerization of
VAc at 60 °C with a long induction period of more than 24 h
(Table 3, entry 1). In addition to the possible causes of such a
behavior that were discussed above, another one could be a slow
reinitiation of the leaving benzyl radical, which is slow to add to
VAc and is therefore a poor choice for the R group. Hence, an
elevated temperature of 70 °C was employed, as shown in
Despite the similarity of Q and e factors (VAc: Q = 0.026 and
e = ꢀ0.88; norbornadiene: Q = 0.051 and e = ꢀ1.48), we
demonstrated that polymerization of VAc was well controlled
with Nb based xanthate CTA, under the optimized conditions.
Indeed, Q and e values should be carefully taken into considera-
tion but only as an estimation, since our reaction parameters
(e.g., temperature, concentration) are different from those reported
in the literature.
ThiolꢀEne. We have recently demonstrated that thiolꢀene
chemistry, in combination with RAFT polymerization, is a
powerful tool for polymer-small molecule conjugations. Thiol-
containing PS was obtained via aminolysis (ω-approach), that
was further modified with a range of low molecular weight ene-
containing compounds. Herein, with the R approach, we prepared
in a direct way a range of Nb-containing semitelechelics, available
for further postpolymerization modifications via thiolꢀene
chemistry. To demonstrate that, PS with Nb end group function-
ality (7) was modified with three different thiol-containing low
molecular weight compounds: dodecanethiol (DdSH, 10),
benzyl mercaptan (BSH, 9) and 2-mercapto propionic acid
(MPA, 8) (Scheme 3). Reaction conditions as well as the results
of the thiolꢀene modification of PS are summarized in Table 4.
Prior to the thiolꢀene reactions, a blank reaction was performed
and the stability of Nb double bond was explored under the UV
light, during an extended irradiation time (i.e., 1 h), which is 2 to
4 times higher than the regular irradiation time employed in our
polymer functionalization systems. The potential conversion of
1
Nb group through self-coupling was analyzed by 500 MHz H
NMR for end group determination, and SEC for determination
of the molecular weights and PDI before and after the blank
reaction. Comparison of the aromatic protons (6.3ꢀ7.3 ppm) to
the Nb protons (6.05 and 6.1 ppm) before and after the
irradiation revealed no reaction occurring at the Nb R-terminus.
The SEC chromatogram showed neither shoulder formation nor
increase in PDI, with number-average molecular weight (Mn)
and peak molecular weight (Mp) being identical before and after
the reaction.
1
Table 3, entries 2 and 3. SEC and H NMR inspections of the
reaction aliquots revealed no monomer conversion during the
first 2 h of the reaction. While only 10% conversion was obtained
during the third polymerization hour, rapid monomer consump-
tion was found in the fourth reaction hour (Table 3, entries 2
and 3). Low monomer conversion (Table 3, entry 2) led to PVAc
All postpolymerization modification reactions were performed
in THF, under 365 nm, with 0.2 equiv of 2,2-dimethoxy-2-
phenylacetophenone (DMPA) as photoinitiator. Initially, 1 equiv
of the thiol-containing low MW compound was employed as
required to address click conditions,73 but only in the case of
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(Table 4, entry 8) while only 20 and 15% when using dodeca-
nethiol and benzyl mercaptan, respectively (Table 4, entries 7
and 9). The choice of the norbornene group is thus highly
preferred over the allyl functional group for thiolꢀene polymer
functionalization.
’ CONCLUSION
We have prepared a new family of norbornenyl (Nb) based
CTAs via an universal synthetic platform, which allows for the
other functional groups to be incorporated as well, such as an allyl
group. Polymerization of styrene, methyl acrylate, 1-ethoxyethyl
acrylate and vinyl acetate was conducted in a controlled fashion,
essentially retaining the Nb and the allyl end groups at the
R-terminus. The optimization of the polymerization conditions
revealed that low temperatures and monomer conversions (e.g.,
below 50% for styrene and vinyl acetate and below 30% for
acrylates) are the key parameters to avoid interference of the Nb
functional group with the propagating radical species. Benefits
that are devoted to the unusual, ring strain promoted reactivity of
the Nb group, were recognized in a rapid polymer postmodi-
fications via radical thiolꢀene reaction. The Nb functional
R-semitelechelic polymers provide a basis upon which advanced
architectures may be built. Further applications of the Nb-based
polymers are under investigation and will be published in the
near future.
Figure 4. 500 MHz 1H NMR (CDCl3) for PS before (upper, Nb
doublet present) and after (bottom, Nb doublet absent) thiolꢀene
modification (entry 4, Table 4).
2-mercaptopropionic acid (8, Scheme 3), an equimolar amount
was sufficient to entirely saturate the Nb double bond (Table 4,
entry 4), leading to successfully modified PS (11, Scheme 3).
Unreacted thiols, if any, were removed during the precipitation of
polymer in cold methanol. Figure 4 shows distinct Nb peaks
decreasing toward the end of the postpolymerization modification
process. Investigations with dodecanethiol (Table 4, entry 1) and
benzyl mercaptan (Table 4, entry 5) revealed significantly lower
functionalization efficiency of 70 and 45%, respectively. These
results are consistent with the findings of Hoyle et al. that thiols
based on mercaptopropionate esters copolymerize with a given
ene more quickly than mercaptoacetate esters, which in turn
reacts more quickly than alkyl thiols.30 However, a 5-fold
equivalent excess in case of both thiols was sufficient to reach
quantitative polymer modification (Table 4, entries 2 and 6).
Moreover, we have shown that a reduced reaction time (Table 4,
entry 3) results in completely modified PS.
’ ASSOCIATED CONTENT
S
Supporting Information. Characterization of polymeri-
b
zation reactions and polymers. This material is available free of
charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: filip.duprez@ugent.be.
The knowledge acquired on small molecules systems30,36,74
suggests that the Nb group is the most reactive double bond
toward thiols. Cramer et al.35,36 reported on the mechanism of
radical thiolꢀene chemistry and have shown that the chain
transfer is the rate limiting step and that the reaction order is
varying with the type of ‘ene’ functional group. While, for
example, the thiol-allyl ether system exhibits a high propagation
to chain-transfer ratio (kp/kct), the thiolꢀNb system was found
to have equivalent propagation (kp) and chain-transfer (kct)
kinetic parameters, and therefore the reaction rates were of 1/2
order regarding both thiol and Nb concentration.35 The high
reactivity of the Nb arises from the release of the ring strain upon
the addition of the thiyl radical onto the Nb double bond.
In order to transfer aforementioned findings to the polymer
systems, besides the Nb-containing PS, we have prepared allyl-
containing PS (Table 2, entries 2 and 3) that serves as a direct
comparison of the reactivity of both Nb and allyl functional
groups. Similarly to Nb-containing PS, we have verified the self-
reactivity of the allyl double bond of allyl-containing PS in typical
thiolꢀene reaction conditions. After 1 h of irradiation time, the
’ ACKNOWLEDGMENT
W.V.C. thanks the Research Foundation—Flanders (FWO)
for a postdoctoral research fellowship. The authors acknowledge
the Belgian Program on Interuniversity Attraction Poles initiated
by the Belgian State, Prime Minister’s office (Program P6/27) for
financial support.
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