Efficient oxidative self-coupling of polystyrene bearing chain-end primary amines

Article abstract of DOI:10.1016/j.polymer.2015.04.032

A series of well-defined linear polystyrenes (PSs) with different degree of polymerization (DP) was synthesized via atom transfer radical polymerization (ATRP) using tert-butyloxycarbonyl (t-boc)-protected 4-(aminomethyl)phenyl 2-bromoisobutyrate (BAPB) a

Full text of DOI:10.1016/j.polymer.2015.04.032

Polymer xxx (2015) 1e5
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Polymer
journal homepage: www.elsevier.com/locate/polymer
Efficient oxidative self-coupling of polystyrene bearing chain-end
primary amines
HyeMi Kim, Hyung-il Lee*
Department of Chemistry, University of Ulsan, Ulsan 680-749, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of well-defined linear polystyrenes (PSs) with different degree of polymerization (DP) was
synthesized via atom transfer radical polymerization (ATRP) using tert-butyloxycarbonyl (t-boc)-pro-
tected 4-(aminomethyl)phenyl 2-bromoisobutyrate (BAPB) as an initiator. The resulting polymers were
deprotected by cleavage of the t-boc protecting groups via treatment with trifluoroacetic acid (TFA) to
generate the chain-end primary amine functionality. The chain-end primary amine groups of the poly-
mers were self-coupled in the presence of 2,20-azobisisobutyronitrile (AIBN) under an oxygen atmo-
sphere via imine bond formation. The coupling efficiency decreased slightly as the chain length of the PS
increased. The imine linkages of the coupled PSs were hydrolyzed in the presence of HCl to individual PS
chains.
Received 28 November 2014
Received in revised form
1 April 2015
Accepted 11 April 2015
Available online xxx
Keywords:
ATRP
Oxidative coupling
AIBN
© 2015 Elsevier Ltd. All rights reserved.
1. Introduction
[22e24], reversible additionefragmentation chain transfer (RAFT)
[25], and nitroxide mediated polymerization (NMP) [26], opening
While ‘controlled/living radical polymerization’ (CRP) offers the
preparation of polymers with predetermined molecular weights
and a narrow molecular weight distribution, functionalization of
polymers synthesized by CRP methods remains an important
challenge in polymer chemistry [1e4]. Functionalization of poly-
mers is important in the field of preparation of telechelic polymers
[5,6], anchoring polymers onto various surfaces [7e9], and bio-
conjugation [10e12]. For these applications, selective functionali-
zation is required so that reactions take place only at specific sites of
the polymer molecule.
While functionality is mostly introduced through prefunction-
alized or protected monomers, the precise synthesis of polymers
containing functional end groups is also important for many ap-
plications. For a successful reaction at the polymer chain end with
high yield, simple, efficient, and versatile chemical reactions should
be used. To these ends, “click” reactions [13,14], such as the Cu-
catalyzed alkyne/azide cycloaddition (CuAAC) [15,16], thiol-ene
[17e19], and DielseAlder [20,21] reactions have recently been
up new opportunities for postpolymerization modification at the
polymer chain end. In addition to click reactions, it is important to
develop more synthetic tools to engineer well-defined macromol-
ecules with specific functionality.
As a radical initiator, azobisisobutyronitrile (AIBN) is used
widely in radical polymerization with oxygen-free environments
because carbon-centered radicals can easily react with oxygen to
form peroxy radicals, which stop the polymer chain from propa-
gating [27]. While oxygen is fatal for radical polymerization initi-
ated by AIBN, peroxy radicals generated by the reaction between
carbon centered radicals and oxygen were found to be useful in
radical-based organic reactions [28e32]. Among them, Fu et al.
reported the highly efficient AIBN initiated self-coupling reaction
where primary amines can be reacted together to form imines
under an oxygen environment [33].
The imine bond has a unique pH-responsive nature [34,35].
When the pH of the solution is reduced, in acidic conditions, the
imine bond decomposes to form an aldehyde and an ammonium
ion. Due to the pH-responsiveness of imine bond, it has been used
as an important component for a dynamic covalent bond that is
widely used in the controlled formation of various supramolecular
systems [36].
used extensively as polymer modification techniques at a- or u-
chain ends. Especially, “click” reactions can be combined with CRP
techniques, such as atom transfer radical polymerization (ATRP)
To our knowledge, there is no report of the synthesis of self-
coupled polymers using oxidative transformation of chain-end
primary amines to imines. Given this background, here, we
* Corresponding author.
E-mail address: sims0904@ulsan.ac.kr (H.-i. Lee).
http://dx.doi.org/10.1016/j.polymer.2015.04.032
0032-3861/© 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kim H, Lee H-i, Efficient oxidative self-coupling of polystyrene bearing chain-end primary amines, Polymer
(2015), http://dx.doi.org/10.1016/j.polymer.2015.04.032

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H. Kim, H.-i. Lee / Polymer xxx (2015) 1e5
report that well-defined polystyrenes with primary amine func-
tionality at the chain end are highly versatile building blocks for
the construction of self-coupled polymers via an AIBN-initiated
oxidative coupling reaction. After the highly efficient self-
coupling reaction, the successful pH-driven cleavage of the imine
bond was also demonstrated, resulting in the formation of indi-
vidual polymers.
2.3.3. Polymerization of styrene from 3 (A1eA3)
Styrene (30.7 mL, 268 mmol), t-boc-4-(aminomethyl)phenyl
2bromo-2-methylpropanoate (0.50g, 1.34mmol), 2,20-Bipyridyl
(0.21 g, 1.34 mmol), and anisole (10 mL) were added to a 50-mL
Schlenk flask equipped with a magnetic stir bar. Oxygen was
removed by three freezeepumpethaw cycles, and CuBr (0.096 g,
0.67 mmol) was added under an argon atmosphere. The polymer-
ization was conducted at 110 ꢁC for 20 h. Samples were removed
periodically by syringe to determine the molecular weight and PDI
by GPC and monomer conversion by 1H NMR spectroscopy. The
polymerization was quenched by cooling and exposing the solution
to air. The catalyst was removed by passing the solution through a
neutral alumina column. The resulting polymer was precipitated by
addition to methanol, and dried under high vacuum at room tem-
2. Experimental
2.1. Materials
Styrene (99%, Aldrich) was purified by passing through a column
filled with basic alumina to remove inhibitors. Di-tert butyl dicar-
perature overnight. 1H NMR (300 MHz, CDCl3,
d in ppm): 7.30e6.24
bonate (ꢀ98%), triethylamine (ꢀ99.5%),
a-bromoisobutyryl bro-
(5H, broad, aromatic), 4.85e4.70 (1H, broad, eCH2eNHeCOOe),
4.30e4.65 (1H, broad, eCH2eCHeBr), 4.28e4.18 (2H, d,
eCeCH2eNHeCOOe), 2.70e0.80 (3H, broad, polymer backbone
part), and 1.48e1.44 (9H, s, eC(CH3)3).
mide (98%), CuBr (98%), and trifluoroacetic acid (99%), were
purchased from Aldrich with the highest purity and were used as
received, with no further purification. 2,20-Azobisisobutyronitrile
(AIBN, Aldrich, 98%) was recrystallized from ethanol. 2,20-Bipyridyl
(ꢀ99.0%) was purchased from Tokyo Chemical Industry (TCI) and
used as received. 4-Hydroxybenzylamine (97%) was purchased
from Matrix Scientific and used as received.
2.3.4. t-Boc deprotection of A1 (B1)
A1 (0.5 g) was dissolved in dichloromethane (10 mL) in a 50-mL
round flask, equipped with a stir bar. To this solution trifluoroacetic
acid (TFA, 5 mL) was injected slowly. The reaction mixture was
stirred at room temperature for 8 h, after which time it was
concentrated in vacuo. The crude solution was diluted with EtOAc,
and washed with Na2CO3 and brine. The organic layer was dried
using anhydrous MgSO4, concentrated, and precipitated by addi-
tion to methanol. The resulting polymer was dried under high
vacuum at room temperature overnight. 1H NMR (300 MHz, CDCl3,
2.2. Instrumentation
1H NMR spectra were collected in CDCl3 on a Bruker Avance
300 MHz NMR spectrometer. The apparent molecular weights and
molecular weight distributions were measured by GPC (Agilent
Technologies 1200 series) using a polystyrene standard, with DMF
as the eluent at 30 ꢁC and a flow rate of 1.00 mL/min.
d
in ppm): 7.30e6.24 (5H, broad, aromatic), 4.30e4.65 (1H, broad,
eCH2eCHeBr), 3.85e3.77 (2H, d, eCeCH2eNHeCOOe), and
2.70e0.80 (3H, broad, polymer backbone part).
2.3. Synthesis
2.3.5. Coupling of B1 (C1)
2.3.1. t-Boc-4-hyroxy benzyl amine (2)
B1 (40 mg, 0.013 mmol, assuming the molecular weight is
3000), AIBN (44 mg, 0.26 mmol), and toluene (1 mL) were added
into a 50-mL round flask equipped with a magnetic stir bar. The
solution was purged with oxygen for 15 min. The solution was
stirred vigorously and heated at 70 ꢁC for 12 h under an oxygen
atmosphere and precipitated into methanol, and dried under vac-
To a solution of the 4-hydroxybenzylamine (2.0 g, 16.2 mmol) in
THF (20 mL) was added TEA (3.4 mL, 24.3 mmol), followed by the
slow addition of di-tert butyl dicarbonate (5.30 g, 24.3 mmol in
20 mL of THF). The reaction mixture was stirred at room temper-
ature for 3 h, after which time the solvent was removed in vacuo.
The crude mixture was partitioned between H2O and diethyl ether.
The organic layer was collected and dried using anhydrous MgSO4.
The solution was filtered, concentrated, and purified by chroma-
tography (hexane:ethyl acetate ¼ 1:2) to provide t-boc-4-hyroxy
uum at 25 ꢁC for 24 h. 1H NMR (300 MHz, CDCl3,
d in ppm):
9.97e9.90 (1H, s, eCeCH]NeCH2e), 8.10e6.24 (5H, broad, aro-
matic), 5.39e5.33 (2H, s, eCeCH]NeCH2e); 4.30e4.65 (1H, broad,
eCH2eCHeBr), 3.85e3.77 (2H, d, eCeCH2eNHeCOOe), and
2.70e0.80 (3H, broad, polymer backbone part).
benzyl amine. 1H NMR (300 MHz, CDCl3,
d in ppm): 7.16e7.10
(2H, d, aromatic), 6.79e6.74 (2H, d, aromatic), 4.83e4.67 (1H,
broad, eCH2eNHeCOOe), 4.27e4.15 (2H, d, eCeCH2eNHe), and
1.46e1.42 (9H, s, eC(CH3)3).
2.3.6. The cleavage of C1
C1 (20 mg in 1 mL DMF) was treated by 0.2 mL of 1 M HCl. The
reaction mixture was stirred at 50 ꢁC for 5 h and precipitated into
methanol. The resulting polymer was dried under high vacuum at
room temperature overnight.
2.3.2. t-Boc-4-(aminomethyl)phenyl 2-bromo-2-methylpropanoate
initiator (3)
t-boc-4-hydroxy benzyl amine (2.72 g, 12.2 mmol), TEA (3.4 ml,
24.3 mmol), and THF (50 mL) were added to a 250-mL round flask
3. Results and discussion
equipped with a stir bar. The flask was cooled in an ice bath. a-
Bromoisobutyryl bromide (3.0 mL, 24.5 mmol in 10 mL of THF) was
injected slowly. The reaction mixture was allowed to proceed in the
ice bath for 30 min and continued for 24 h at room temperature.
The product was collected, washed with THF, and filtered. The
filtrate was dried under reduced pressure and the crude product
was recrystallized from hexane to yield white crystals with a yield
The synthesis of tert-butyloxycarbonyl (t-boc)-protected 4-
hydroxybenzylamine (2) involved the reaction of di-tert butyl
dicarbonate with 4-hydroxybenzylamine (1) in the presence of
triethylamine (TEA) in THF. Compound 2 reacted with a-bromoi-
sobutyryl bromide to yield a target initiator, 3. 1H NMR spectra
confirmed the successful synthesis of 2 and 3 (Fig. S1).
of 58.1%. 1H NMR (300 MHz, CDCl3,
d
in ppm): 7.35e7.27 (2H, d,
The strategy used is illustrated schematically in Scheme 1. ATRP
was used to directly prepare a series of polystyrenes (PSs) poten-
tially containing terminal primary amine with a controlled molec-
ular weight and low polydispersity. A CuBr/bpy catalyst system was
aromatic), 7.10e7.03 (2H, d, aromatic), 4.88e4.79 (1H, broad,
eCH2eNHeCOOe), 4.33e4.25 (2H, d, eCeCH2eNHe), 2.07e2.02
(6H, s, eCe(CH3)2Br), and 1.46e1.42 (9H, s, eC(CH3)3).
Please cite this article in press as: Kim H, Lee H-i, Efficient oxidative self-coupling of polystyrene bearing chain-end primary amines, Polymer
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H. Kim, H.-i. Lee / Polymer xxx (2015) 1e5
3
Scheme 1. Synthesis of a) latent primary amine initiator, 3 and b) coupling of chain-end primary amine groups of polystyrene prepared by ATRP.
used for the ATRP of styrene using compound 3 as an initiator in
anisole. Samples were removed at regular intervals during poly-
merization to obtain A1eA3 polymers with different molecular
weights as well as to monitor conversion and molecular weight
evolution. The polymerization was stopped at 50% monomer con-
version and the molecular weight and molecular weight distribu-
tion of the resulting PSs were obtained using a gel permeation
chromatography (GPC) DMF line with polystyrene standards (Fig. 1,
Table 1).
Deprotection of t-boc groups was accomplished by reacting
A1eA3 polymers with trifluoroacetic acid (TFA) in dichloro-
methane. 1H NMR spectroscopy confirmed the successful depro-
tection of A1, as monitored by the disappearance of the t-boc peaks
at 1.2e1.3 ppm and the appearance of the eCH2NH2 peak at
3.8 ppm (Fig. 2). The apparent molecular weight of B1 did not
change after deprotection, suggesting that deprotection did not
lead to change in hydrodynamic volumes in DMF. A2 and A3 were
also deprotected successfully to yield B2 and B3, respectively
(Figs. S2 and S3).
Having obtained B1eB3 polymers with chain-end primary amine
functionality, self-coupling reactions of these polymers were
investigated. The chain-end primary amine groups of the polymers
(B1eB3) were reacted together to form imine bond in the presence
of AIBN under an oxygen atmosphere, leading to self-coupled poly-
mers, C1eC3. For all reactions, a 20-fold molar excess of AIBN over
primary amine functionalized polymers (B1eB3) was used to ensure
high conversion. 1H NMR spectroscopy confirmed imine formation
of C1 by the appearance of the new peaks (f and g), representing
protons of imine groups at 9.9 and 5.2 ppm and the complete
disappearance of peak e at 3.8 ppm, indicating the successful con-
version to C1 (Fig. 2). Similarly, the successful syntheses of C2 and C3
were confirmed by 1H NMR spectroscopy (Figs. S2 and S3).
The influence of molecular weight on the coupling efficiency
was assessed by GPC (Fig. 3). As evidenced by 1H NMR spectros-
copy, the successful self-coupling reaction was further confirmed
by GPC analysis, with Mn of self-coupled polymers (C1eC3) being
increased, almost twice that of the precursor polymers (B1eB3).
Table 1
Summary of DMF GPC results and efficiency of self-coupling reactions.
PDIb
Ycoupling
a
c
Mn,
(g/mol)
Mn,
b (g/mol)
app
theory
A-1
B-1
C-1
A-2
B-2
C-2
A-3
B-3
C-3
3000
3000
6000
6000
6000
12 000
10 000
10 000
20 000
3500
3600
6000
6600
5800
1.06
1.06
1.17
1.07
1.11
1.10
1.11
1.12
1.14
e
e
80
e
e
9400
77
e
11 500
10 660
16 400
e
70
a
Theoretical molecular weight determined from monomer conversions.
Apparent number-average molecular weight and PDI determined by DMF GPC
b
with PS calibration.
c
Fig. 1. DMF GPC traces of A1, A2, and A3.
Determined by apparent number-average molecular weight.
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H. Kim, H.-i. Lee / Polymer xxx (2015) 1e5
Fig. 2. 1H NMR spectra of A1, B1, and C1.
Fig. 3. GPC traces for a primary amine-containing polystyrenes and their self-coupled products.
Please cite this article in press as: Kim H, Lee H-i, Efficient oxidative self-coupling of polystyrene bearing chain-end primary amines, Polymer
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H. Kim, H.-i. Lee / Polymer xxx (2015) 1e5
5
Scheme 2. Formation of individual polymers by the cleavage of the imine bond under acidic conditions.
The molecular weight distribution of the self-coupled polymers
remained as narrow as Mn/Mw ¼ 1.1e1.17. As seen in Fig. 3a, the
self-coupling of the parent polymer B1 (Mn ¼ 3600 g/mol, Mn/
Mw ¼ 1.06) resulted in a polymer C1 with high molecular weight
(Mn ¼ 6000 g/mol) and a broad molecular weight distribution (Mn/
Mw ¼ 1.17). As the chain length of the parent polymers was larger, a
low shift towards the high molecular region in the apparent mo-
lecular weight was observed (Fig. 3b and c). Based on an increase in
the apparent Mn values, the coupling efficiencies of B1, B2, and B3
were calculated to be 80, 77, and 70%, respectively. As expected, the
self-coupling efficiency decreased as the molecular weight of the
polymer increased. When the primary amine-terminated linear PS
had a higher molecular weight, the effect of relatively low chain-
end group concentration decreased the self-coupling efficiency.
Table 1 summarizes the results of self-coupled polymers with
differing molecular weights.
weight of polystyrenes, the coupling efficiency was >70%. The acid-
catalyzed decomposition of selfcoupled polymers into individual
polymers was also demonstrated. This oxidative coupling and
decoupling strategy, combined with ATRP and efficient post-
polymerization functionalization, represents a modular route to
well-defined functional polymers.
Acknowledgments
This work was supported by the Priority Research Center Pro-
gram (2009-0093818) and the Basic Science Research Program
(NRF-2014R1A1A2057197) through the National Research Foun-
dation of Korea, funded by the Ministry of Education, Science, and
Technology of Korea.
Appendix A. Supplementary data
Due to the pH-responsive nature of the benzoic imine bond, the
self-coupled polymers can decompose into individual polymers
under acidic condition. One of the decomposed polymers has an
aldehyde group in the chain end and the other has an ammonium
ion (Scheme 2). After treatment with HCl, the GPC traces shifted
towards lower molecular weights (Fig. 4). These results indicated
the successful pH-driven cleavage of the imine bond, which, in turn,
leads to the formation of individual polymers.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.polymer.2015.04.032.
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Fig. 4. DMF GPC traces of C2 and its hydrolyzed product after treatment with HCl.
Please cite this article in press as: Kim H, Lee H-i, Efficient oxidative self-coupling of polystyrene bearing chain-end primary amines, Polymer
(2015), http://dx.doi.org/10.1016/j.polymer.2015.04.032