Synthesis of cyclic polyelectrolyte via direct copper(I)-catalyzed click cyclization

Article abstract of DOI:10.1002/pola.25869

Well-defined cyclic poly(acrylic acid) (PAA) has been successfully prepared based on the direct click cyclization. The linear poly(tert-butyl acrylate) (PtBA) with azide and TMS-protected alkyne group forms cyclic chain directly by the copper(I)-catalyzed click cyclization without any deprotection steps. Cyclic PAA is synthesized by the hydrolysis of cyclic PtBA. The present synthetic strategy provides a simple and efficient method to synthesize cyclic polyelectrolyte and can be applied to other polymer systems. Copyright

Full text of DOI:10.1002/pola.25869

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Synthesis of Cyclic Polyelectrolyte via Direct Copper(I)-Catalyzed
Click Cyclization
Fenggui Chen,1 Guangming Liu,1 Guangzhao Zhang2
1Hefei National Laboratory for Physical Sciences at the Microscale, Department of Chemical Physics, University of Science and
Technology of China, Hefei 230026, China
2Faculty of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, China
Correspondence to: G. M. Liu (E-mail: gml@ustc.edu.cn)
Received 12 October 2011; accepted 29 November 2011; published online 13 December 2011
DOI: 10.1002/pola.25869
KEYWORDS: atom transfer radical polymerization (ATRP); click reaction; macrocycles; polyelectrolytes; tert-butyl acrylate
INTRODUCTION Polyelectrolyte has received extensive atten-
tion due to its promising applications in various fields.1 As
the properties of polyelectrolyte are generally determined by
its conformation,2 cyclic polyelectrolyte is expected to exhibit
some unique properties in comparison with the linear one.3
However, due to the challenge in synthesis of cyclic polyelec-
trolyte, the experimental studies on such special polymer are
rarely reported.4 A feasible method to synthesize cyclic poly-
electrolyte should be based on the ionization of its neutral
precursor as the electrostatic repulsion would prevent the
direct cyclization of the linear polyelectrolyte chain.5
Recently, Cuevas et al.20 developed a direct click reaction of
azide with TMS-protected alkyne group by using copper (I)
bromide/triethylamine (CuBr/TEA) as the catalyst complex.
Such direct copper(I)-catalyzed click reaction without any
deprotection steps is expected to be more convenient and ef-
ficient than the traditional method in the synthesis of cyclic
polymer. However, to the best of our knowledge, this reac-
tion has not been used in polymer synthesis yet. In the pres-
ent work, we have successfully prepared cyclic poly(acrylic
acid) (PAA) from its neutral precursor (i.e., cyclic PtBA),
which is synthesized directly via the copper(I)-catalyzed
click cyclization with azide and TMS-protected alkyne groups
at the ends of linear PtBA.
On the other hand, although a number of attempts have
been devoted to the synthesis of cyclic polymer,6–9 design
and development of new synthetic methods are still the im-
portant subjects in this area.8 Currently, the ring-closure
reaction of linear precursor with two complementary reac-
tive terminal groups in dilute solution has been extensively
used to synthesize cyclic polymer.9–13 Huisgen 1,3-dipolar
cycloaddition reaction of organic azide and alkyne proves to
be efficient in the cyclization of linear polymer due to the
high reactivity between such two groups and the low suscep-
tibility to side reactions.11,14,15 The linear precursor is usu-
ally prepared by atom transfer radical polymerization
(ATRP), because the terminal Br group can be readily con-
verted into azide with a reasonable yield.16–18 The alkynyl-
containing initiator is generally protected with tetramethylsi-
lane (TMS) or triisopropylsilane (TIPS) so that the side reac-
tions in the following polymerization are eliminated, espe-
cially in the synthesis of cyclic poly(tert-butyl acrylate)
(PtBA).18,19 TMS or TIPS is usually removed using tetrabuty-
lammonium fluoride (TBAF) for the next click cyclization.
However, the azide groups are often detached from the ends
of polymer chains in the deprotection process, which would
prevent the next click cyclization.
RESULTS AND DISCUSSION
Synthesis of Linear PtBA
When propargyl 2-bromoisobutyrate (HACBCABr) was used
to initiate the polymerization of t-BA with CuBr and
N,N,N0,N00,N00-pentamethyldiethylenetriamine (PMDETA) as the
catalyst, the product will have a small amount of undesirable
large molecular weight polymer due to the radical polymer-
ization of alkyne. To eliminate the side reactions, TMS-pro-
tected initiator (TMSACBCABr) was used. The well-defined
PtBA with TMS-protected alkyne group was obtained via
ATRP with CuBr/PMDETA as the catalyst in acetone at 60
ꢀC.21 The characterization of the polymers is listed in Table 1.
The bromine groups at the ends of linear PtBA chains were
converted into azide groups via nucleophilic substitution in
dimethylformamide (DMF) in the presence of an excess of
NaN3 (Scheme 1). After the reaction, the solution was passed
through neutral alumina to remove the excessive sodium
azide (NaN3). Gel permeation chromatograph (GPC) traces in
Figure 1(a) show that the elution peak of TMSACB
CAPtBAAN3 is almost the same as that of TMSACBCA
Additional Supporting Information may be found in the online version of this article.
C
V
2011 Wiley Periodicals, Inc.
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TABLE 1 Characterization of Linear and Cyclic PtBA
Intramolecular Cyclization of Linear PtBA
As the click reaction favors the intramolecular cyclization
b
b
when the polymer concentration is below 0.1 mmol Lꢁ1 16
,
Mn (g/mol)
Mw/Mn
Polymerization
the TMSACBCAPtBAAN3/DMF mixture was added dropwise
to a DMF solution containing CuBr and TEA (ligand) using a
microliter syringe (Scheme 1). The molar ratio of the catalyst
to the reactive end group was about 100 so that the click
reaction was complete. GPC measurements demonstrate that
cyclic PtBA has a higher elution time than the linear one as
the cyclic polymer has a more compact structure with a
smaller hydrodynamic volume [Fig. 1(a)]. In Figure 1(b), in
comparison with the linear precursor, peaks a0 and b0 ini-
tially at 4.65 and 3.64 ppm disappear and new peaks at 5.18
ppm (a00 þ b00) and 7.74 ppm (c00) appear in the 1H NMR
spectrum of cyclic PtBA after the click cyclization, implying
that the cyclization of linear PtBA is successful, because the
new peaks are attributed to the triazole ring. The intramo-
lecular end-to-end click cyclization was also confirmed by
FTIR. Figure 1(c) shows the disappearance of characteristic
azide absorbance peak at 2109 cmꢁ1 and the appearance of
characteristic 1,2,3-triazole absorbance peak at 3300 cmꢁ1
in the spectrum of cyclic PtBA, indicating that all the azides
participate into the formation of triazole ring with TMS-pro-
tected alkyne groups. Clearly, well-defined cyclic PtBA was
successfully synthesized by the direct copper(I)-catalyzed
click cyclization without any deprotection steps. Note that if
the cyclic PtBA was synthesized using the traditional
method, the azide groups were often detached from the ends
of PtBA chains in the deprotection process, which would pre-
vent the next click cyclization (see Fig. S1 in Supporting In-
formation). In addition, Table 1 shows that the narrowly dis-
tributed cyclic PtBA with different molecular weights can be
prepared using the same method (also see Fig. S2 in
Samplea
Time (h)
Linear
Cyclic
Linear
Cyclic
PtBA1
PtBA2
PtBA3
a
5
3
1
6300
4200
1700
4700
3500
1600
1.07
1.08
1.02
1.06
1.09
1.01
The polymerizations were carried out at 60 ꢀC with the feed molar
ratio of [Initiator]0/[CuBr]0/[PMDETA]0/[Monomer]0 ¼ 1:1:1:60.
b
Determined by GPC.
PtBAABr. 1H NMR spectra of TMSACBCAPtBAABr and
TMSACBCAPtBAAN3 are shown in Figure 1(b). For
TMSACBCAPtBAABr, the peak a at 4.65 ppm is ascribed to
methylene protons (2H) of propargyl residues, and the peak b
at 4.10 ppm is ascribed to methine proton (1H) adjacent to
the terminal bromide. For TMSACBCAPtBAAN3, a new peak
at 3.64 ppm (b0) corresponding to the methine proton adja-
cent to the terminal azide group comes out and the peak
b disappears. The integration ratio of a0:b0 is nearly 2:1,
which is consistent with the structure of TMSACB
CAPtBAAN3. The facts indicate that the terminal bromine
groups are completely converted into azides. FTIR in Figure
1(c) shows TMSACBCAPtBAAN3 has a new band at 2109
cmꢁ1 compared with TMSACBCAPtBAABr, further indicating
the existence of terminal azide groups. It is worth noting that
we have also tried the TMS deprotection before the azidation
reaction.11 However, this reaction sequence requires to precip-
itate PtBA in the mixture of CH3OH/H2O several times to
remove the unreacted TBAF and the detached TMS during pu-
rification, which will result in a low yield of linear precursor.
SCHEME 1 Strategy of synthesis of cyclic PAA.
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high molecular weight byproducts, which is due to the high
reactivity between azide and alkyne groups and the low sus-
ceptibility to side reactions. Besides, the low concentration
(below 0.1 mmol Lꢁ1) of the linear precursor used in the
click reaction also favors the intramolecular cyclization. How-
ever, for the linear precursor with larger molecular weight
(e.g., 7200 g molꢁ1), an undesirable high molecular weight
byproduct was produced during the cyclization (see Fig. S2
in Supporting Information).
Hydrolysis of Cyclic PtBA
The hydrolysis of cyclic PtBA was carried out in the solution
of trifluoroacetic acid (TFA)/CH2Cl2 at room temperature.22
Conversion of cyclic PtBA into cyclic PAA was ascertained by
1H NMR and FTIR (Fig. 2). As can be seen from Figure 2(a),
the peak (f) at 1.44 ppm originating from tert-butyl groups
of PtBA disappears in the 1H NMR spectrum of cyclic PAA,
indicating the complete hydrolysis of such groups. Figure
2(b) shows the characteristic peak of carbonyl of ester group
at 1732 cmꢁ1 in cyclic PtBA shifts to 1716 cmꢁ1, which is
FIGURE 1 Characterization of linear and cyclic PtBA. (a) GPC
traces of (I) TMSACBCAPtBA-Br, (II) TMSACBCAPtBAAN3, and
(III) cyclic PtBA; (b) 1H NMR spectra of (I) TMSACBCAPtBAABr,
(II) TMSACBCAPtBAAN3, and (III) cyclic PtBA; (c) FTIR spectra
of (I) TMSACBCAPtBAABr, (II) TMSACBCAPtBAAN3, and (III)
cyclic PtBA.
Supporting Information). Actually, for the linear precursor
with relatively low molecular weights, the cyclic polymer
chain can be successfully prepared without the undesirable
FIGURE 2 Characterization of cyclic PtBA and cyclic PAA. (a)
1H NMR spectra of (I) cyclic PtBA and (II) cyclic PAA; (b) FTIR
spectra of (I) cyclic PtBA and (II) cyclic PAA.
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ascribed to the carbonyl of carboxyl group. In addition, a
broad peak from 2500 to 3300 cmꢁ1 is attributed to hydroxyl
from the carboxyl group. All the aforementioned results indi-
cate that the cyclic PtBA is completely converted into cyclic
PAA. Additionally, our preliminary experiments demonstrate
that the cyclic PAA chains actually exhibit quite different prop-
erties compared with the linear ones. For example, the intrin-
sic viscosities for the cyclic (Mn ꢂ 3200 g molꢁ1) and linear
mL, 2.0 mmol) in CH2Cl2 (10.0 mL) was added dropwise to a
solution of 3-trimethylsilyl-2-propyn-1-ol (2.6 g, 2ꢀ0 mmol)
and TEA (3.5 mL, 2.4 mmol) in THF (30.0 mL) at 0 C. After-
ward, the mixture was allowed to stir for 24 h at room tem-
perature. The resulted triethylammonium salts were filtrated
out, and the solvent was removed by rotary evaporation. The
crude product was dissolved in CH2Cl2 and washed twice
with saturated NH4Cl solution and twice with water. The or-
ganic layer was dried using anhydrous MgSO4, and the solvent
was removed in vacuo, yielding dark brown oil. The crude
product was passed through a silica-gel column using hex-
ane/ethyl acetate (95:5) mixture as the eluent. The final prod-
uct was isolated as colorless oil and dried under vacuum.
(Mn ꢂ 4000 g molꢁ1) PAA are ꢂ0.10 and ꢂ0.16 dL gꢁ1
,
respectively, at room temperature. The GPC measurements
show that the cyclic PAA chain has a smaller hydrodynamic
radius than that of the linear PAA chain with the same degree
of polymerization, because the former has a higher elution
time (see Fig. S3 in Supporting Information). In addition,
quartz crystal microbalance experiments demonstrate that the
multilayer formed by the cyclic PAA is quite different from
that of linear PAA (see Fig. S4 in Supporting Information).
1H NMR (400 MHz, CDCl3, d, ppm): 4.76 (s, 2H, ACH2AO2C),
1.97 (s, 6H, O2CAC(CH3)2Br), 0.18 (s, 9H, (CH3)3Si); 13C NMR
(400 MHz, CDCl3, d, ppm): 171.23 (OAC(¼¼O)), 93.14, 98.50
((CH3)3SiACBCACH2), 55.50 (O2CAC(CH3)2ABr), 54.60
(BACH2AO2C), 31.02 (O2CAC(CH3)2ABr).
EXPERIMENTAL
Synthesis of Br-Terminated PtBA (TMSACBCAPtBAABr)
TMSACBCABr (277 mg, 1.0 mmol), t-BA (8.7 mL, 60.0
mmol), PMDETA (208 lL, 1.0 mmol), CuBr (143 mg, 1.0
mmol), and acetone (2.2 mL) were added into a 25 mL glass
tube. After three freeze–vacuum–thaw cycles, the tube was
sealed under vacuum and then immersed in an oil bath ther-
mostated at 60 ꢀC. After a certain time, the polymerization
was quenched by rapidly cooling the mixture to room tem-
perature and exposing it to air. The mixture was filtered
through neutral alumina to remove the catalyst using THF as
the eluent. The polymer was precipitated by pouring the so-
lution into the mixture of CH3OH and H2O (1:1/v:v). The
Materials
Chlorotrimethyl silane (TMS-Cl) was distilled over CaH2
under reduced pressure prior to use. Tert-butyl acrylate
(t-BA, Aldrich) was passed through a column of alumina to
remove inhibitor, and then distilled over CaH2 under reduced
pressure prior to use. CuBr (AR grade) was stirred in glacial
acetic acid, washed with ethanol, and then dried in a vacuum
oven. Triethylamine (TEA) was stirred with KOH for 12 h at
room temperature, refluxed with toluene-4-sulfonylchloride,
and distilled before use. Tetrahydrofuran (THF) was refluxed
in the presence of Na wire, and then distilled prior to use.
DMF was dried with anhydrous MgSO4 and distilled under
reduced pressure prior to use. Acetone was refluxed in the
presence of a small amount of KMnO4 and then distilled
ꢀ
product was dried under vacuum at 40 C.
Synthesis of Azide End-Functionalized PtBA
(TMSACBCAPtBAAN3)
from
a purple sodium ketyl solution. Dichloromethane
(CH2Cl2) was distilled under nitrogen over CaH2. PMDETA
(Aldrich), butyl lithium (BuLi, 1.6 M in hexane), 2-bromoiso-
butyryl bromide (Aldrich), and sodium azide (NaN3; Acros)
were used as received. The water used was purified by filtra-
tion through Millipore Gradient system after distillation, giv-
ing a resistivity of 18.2 MX cm.
TMSACBCAPtBA-Br (0.2 mmol), NaN3 (130 mg, 2.0 mmol),
and DMF (5.0 mL) were added into a 25-mL round-bottomed
flask with a magnetic stirrer, and the mixture was stirred at
room temperature for 24 h. Afterward, the mixture was diluted
with CH2Cl2 and washed four times with water. The solution
was concentrated in vacuum, and polymer was precipitated by
pouring the solution into the mixture of CH3OH and H2O (1:1/
v:v). The product was dried under vacuum at 40 ꢀC.
Synthesis of 3-Trimethylsilyl-2 propynyl-2-bromo-2-
methylpropanoate (TMSACBCABr)
3-Trimethylsilyl-2-propyn-1-ol was synthesized as follows. A
Synthesis of Cyclic PtBA
solution of propargyl alcohol (1.2 mL, 20.0 mmol) in THF
DMF (200 mL) was added into a 250-mL round-bottomed
flask and degassed by three freeze–pump–thaw cycles. After
the flask was evacuated and refilled with N2, 287 mg of
CuBr (2.0 mmol) and 576 mg of TEA (2.0 mmol) were intro-
duced. The linear precursor (TMSACBCAPtBAAN3) (0.02
mmol) in 10.0 mL of DMF was degassed by three freeze–
pump–thaw cycles. Then this solution was added to CuBr/
TEA mixture at 100 ꢀC via syringe pump at a rate of 0.5
mL/h. After the addition of polymer solution, the reaction
was allowed to proceed for another 6 h. The mixture was
then cooled to room temperature, concentrated in vacuo, and
diluted with CH2Cl2 (100.0 mL). The organic layer was
washed twice using saturated NaHSO4 solution, dried over
anhydrous MgSO4, filtered through neutral alumina to
ꢀ
(150.0 mL) was cooled down to ꢁ78 C, and BuLi (1.6 M in
hexane, 27.5 mL, 44.0 mmol) was added dropwise within 60
min. Then, TMS-Cl (5.8 mL, 45.0 mmol) was added dropwise
to the mixture. The mixture was heated to room temperature
and stirred for another 2 h. A total of 50 mL of hydrochloric
acid solution (2.0 M) was introduced, and then the reaction
was stirred for another 1 h. The aqueous layer was washed
with diethyl ether twice and the combined organic layers
were washed with NaHCO3 and brine and dried over
Na2SO4. The crude product was isolated as yellow oil and
used without further purification.
3-Trimethylsilyl-2-propynyl
2-bromo-2-methylpropanoate
was synthesized as follows. 2-Bromoisobutyryl bromide (3.0
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REFERENCES AND NOTES
remove the catalyst, and concentrated under vacuum. The
cyclic polymer was obtained by precipitation in the mixture
of CH3OH and H2O (1:1/v:v).
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On the basis of the direct copper(I)-catalyzed click cycliza-
tion without any deprotection steps, we have successfully
synthesized well-defined cyclic PtBA and PAA. The cyclic
PtBA and PAA are confirmed by the GPC, NMR, and FTIR
measurements. The present synthetic strategy provides a
convenient and efficient method to synthesize cyclic polye-
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