Synthesis of soluble core cross-linked polystyrene star polymer by application of acrylate-nitrile oxide 'click chemistry' using metal-free reagents

Article abstract of DOI:10.1039/c3gc41722k

In the present work, we have established a novel and environmentally benign method, whereby a 1,3-dipolar cycloaddition reaction has been applied using a non-toxic reagent, iodosobenzenediacetate [PhI(OAc)₂], instead of the conventional copper-based reagents for the development of star-branched polymers. Here we have demonstrated the synthesis of core cross-linked star (CCS) polymers via the formation of isoxazoline ring using 'click reaction' between acrylate functionalities in a polymer chain and in situ generated nitrile oxide groups from a cross-linker added externally. In the initial step, a well-defined styrenic block copolymer with acrylate-functionalized middle-block was synthesized by controlled radical polymerization (RAFT) using α,α′-xylyl-bis(dithiobenzoate) as a chain transfer agent using 4-vinyl benzyl chloride and styrene as comonomers. Thereafter, the chlorobenzyl groups were converted into acrylate by reaction with acrylic acid. In the following step, core cross-linked star (CCS) polymers were synthesized by reacting the above block copolymer and oxime-functionalized cross-linkers (bi- and tetra-functional) using PhI(OAc)₂ 'click chemistry'. Formation of CCS polymers was confirmed from NMR, FTIR, GPC and DLS studies.

Full text of DOI:10.1039/c3gc41722k

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PAPER
Synthesis of soluble core cross-linked polystyrene
star polymer by application of acrylate-nitrile
oxide ‘click chemistry’ using metal-free reagents†
Cite this: Green Chem., 2014, 16,
1365
Rakesh Banerjee, Saikat Maiti and Dibakar Dhara*
In the present work, we have established a novel and environmentally benign method, whereby a 1,3-
dipolar cycloaddition reaction has been applied using a non-toxic reagent, iodosobenzenediacetate [PhI-
(OAc)2], instead of the conventional copper-based reagents for the development of star-branched poly-
mers. Here we have demonstrated the synthesis of core cross-linked star (CCS) polymers via the for-
mation of isoxazoline ring using ‘click reaction’ between acrylate functionalities in a polymer chain and
in situ generated nitrile oxide groups from a cross-linker added externally. In the initial step, a well-
defined styrenic block copolymer with acrylate-functionalized middle-block was synthesized by con-
trolled radical polymerization (RAFT) using α,α’-xylyl-bis(dithiobenzoate) as a chain transfer agent using
4-vinyl benzyl chloride and styrene as comonomers. Thereafter, the chlorobenzyl groups were converted
into acrylate by reaction with acrylic acid. In the following step, core cross-linked star (CCS) polymers
were synthesized by reacting the above block copolymer and oxime-functionalized cross-linkers (bi- and
tetra-functional) using PhI(OAc)2 ‘click chemistry’. Formation of CCS polymers was confirmed from NMR,
FTIR, GPC and DLS studies.
Received 21st August 2013,
Accepted 1st November 2013
DOI: 10.1039/c3gc41722k
www.rsc.org/greenchem
micro-gels. The pioneering works based on a metal free
degradable well-defined polyester based core cross-linked star
Introduction
1,3-Dipolar cycloaddition (1,3-DC) is an effective tool for the polymer by Wiltshire and Qiao7 and redox responsive star
synthesis of highly functionalized organic compounds as well polymer assembly by Sumerlin et al.8 are noteworthy. In the
as complex architectures that have found significant research context of CCS polymers, the innovative works based on
interest in the field of materials science and nanotechnology. the concept of dynamic covalent chemistry (DCC)9 include
Alkyne–azide click chemistry1 is one such tool and has been the synthesis of the CCS polymer through reversible
widely applied for the development of novel polymeric archi- imine bond formation by Fulton et al.10 and star-like polymer
tectures, drug delivery systems, as well as in the synthesis of nano-gels via incorporation of alkoxy-amine units by Otsuka
dendrimers.2 Core cross-linked star (CCS)3 polymers have et al.11
found applications as chemical sensors, carriers of small
In recent years, ‘click chemistry’1 has attracted a great deal
molecules, in tissue engineering, cosmetics, catalysis and of attention in the field of synthetic polymer chemistry. Syn-
other fields.4 There has been a growing importance of CCS thesis of star-polymers has been reported using copper cata-
polymers, dendrimers and hyper-branched polymers5 owing to lyzed alkyne–azide cycloaddition leading to 1,2,3-triazole
a tremendous growth in the field of soft materials. CCS poly- formation.12 However, complete removal of copper from the
mers are the simplest form of branched polymers, where the bulk gel is a challenge, and owing to the cytotoxicity of copper,
branches are extended from a single point.6 Three general such methods may not be suitable for development of
strategies have been applied for the synthesis of star polymers materials for biological applications. Thus the synthesis of
– (i) arm-first (convergent) approach; (ii) core-first (divergent) branched or core cross-linked star (CCS) polymer architectures
approach; and (iii) a combination of these two techniques using mild environmentally friendly reagents is at the fore-
involving the formation of tightly cross-linked nano-gels or front of polymer research. Hypervalent iodine(III) reagents13
such as iodosobenzenediacetate (PhI(OAc)2) has received con-
siderable attention due to its reasonably high activity towards
oxidative organic reaction, along with its easy availability and
non-toxic nature. This unique combination of properties offers
promising applications of this reagent towards metal-free oxi-
Department of Chemistry, Indian Institute of Technology Kharagpur,
West Bengal 721302, India. E-mail: dibakar@chem.iitkgp.ernet.in, dibakar@live.in;
Fax: +91-3222-282252; Tel: +91-3222-282326
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
dative reaction.
c3gc41722k
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In this work, we have developed a unique method for the molecular weights were calculated using polystyrene stan-
synthesis of polystyrene-based CCS polymers through the for- dards. Dynamic light scattering measurements were per-
mation of an isoxazoline14 ring using copper-free nitrile oxide- formed using Malvern Zetasizer Nano equipment with a
alkene 1,3-dipolar cycloaddition (1,3-DC) reactions. RAFT, 3.0 mW He–Ne laser operated at 633 nm. Analysis was per-
which is one of the most versatile controlled polymerization formed at an angle of 173° and a constant temperature of
techniques,15 has been employed for the controlled synthesis 25 °C.
of well-defined styrenic triblock copolymers with a chloro-
methyl functionalized middle-block. Appropriate modification
of the functional group resulted in an acrylate-functionalized
middle-block that was subsequently utilized to form the tar-
geted CCS polymers using bifunctional and tetra-functional
cross-linkers through isoxazoline formation in a 1,3-dipolar
cycloaddition (‘click’) reaction using non-toxic reagent, PhI-
(OAc)2,16 instead of a conventional copper catalyst. Hence, in
this work we have demonstrated the successful utilization of a
relatively simple, environmentally friendly method to form the
CCS architectures, thereby widening the scope of well-known
cyclo-addition reactions towards the development of important
materials, especially those with potential biological
applications.
Synthesis of acrylate-functionalized block copolymer
(Scheme 1)
Synthesis of poly(4-vinylbenzyl chloride) macro-CTA
(P1). α,α′-Xylyl-bis(dithiobenzoate) (XBDTB)18 (0.187 g,
0.481 mmol) and AIBN (20 mg, 0.12 mmol) were mixed with
4-vinylbenzyl chloride (5.0 g, 32.8 mmol), diluted with 1,4-
dioxane (∼2 mL) in a 25 mL round-bottomed (r. b.) flask and
purged with nitrogen for 30 min, following which the reaction
mixture was heated to 80 °C and stirred for 20 h. Thereafter,
the polymerization was quenched, and the product isolated by
precipitation in ice-cold methanol followed by drying under
high vacuum. Polymer P1 was thus obtained as a pink solid
(∼72% yield). FT-IR (KBr, cm−1): 708, 830, 1290, 1420, 1560,
1568, 1610, and 2830. 1H NMR (CDCl3): δ 1.42 (br, CHCH2
polymer backbone), 1.84 (br, CHCH2 polymer backbone), 4.5
(br, –CH2Cl, polymer), 6.78 (br, Ar, polymer), 7.07 (br, Ar,
polymer) [see ESI, Fig. S1†].
Experimental
Materials and methods
Synthesis of polystyrene-block-poly(4-vinylbenzyl chloride)
Styrene, AIBN, 4-vinylbenzyl chloride, acrylic acid and penta- (P2). P1 (0.5 g, 0.093 mmol) and AIBN (3.6 mg, 0.020 mmol)
erythritol were purchased from Sigma-Aldrich and used as were added to a 25 mL r. b. flask. Styrene (0.963 g, 9.3 mmol)
received. All the other chemicals and solvents were purchased was then added followed by addition of 1.0 mL of 1,4-dioxane.
from SRL and Spectrochem (India) and purified by a standard The reactor was then degassed, purged with nitrogen, followed
procedure.17 NMR spectra were recorded in CDCl3 and DMSO- by heating at 70 °C for 24 h. The polymerization was then
d6 and were calibrated using TMS as the internal standard. quenched and the polymer recovered by precipitation in ice-
Molecular weight and polydispersity index (PDI) of the poly- cold hexane followed by filtration and drying to obtain
mers were determined by a GPC instrument (Viscotek) using polymer P2 as a pale pink solid (78% yield). FT-IR (KBr, cm−1):
RI detector and THF as eluent of flow rate 1 mL min−1. The 470, 780, 960, 1290, 1420, 1490, 1580, 1610, 2830, and 3021.
Scheme 1 Synthetic route to acrylate-functionalized block copolymer (P2a).
1366 | Green Chem., 2014, 16, 1365–1373
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Scheme 2 The synthetic route used to prepare oxime-functionalized cross-linkers.
1H NMR (CDCl3): δ 1.45 (br, CHCH2 polymer backbone), 1.86 1280, 1470, and 2990. 1H NMR (CDCl3): δ 3.57 (s, 8H). 13C
(br, CHCH2 polymer backbone), 4.5 (br, –CH2Cl, polymer), NMR (CDCl3): δ 34.4, 43.1 [see ESI, Fig. S3†]. HRMS (ESI+) m/z:
6.78 (br, Ar, polymer), 7.07 (br, Ar, polymer) [see ESI, Fig. S2†].
384.7437 (calculated for [M + H]+: 384.4509).
Synthesis of acryloyl-functionalized block copolymer (P2a).
Preparation of tetra-arm aldehyde (2). 4-Hydroxybenzalde-
Acrylic acid (0.18 g, 2.5 mmol) was taken in a 50 mL two neck hyde (2.517 g, 20.6 mmol) in 25 mL of dry DMF was treated
r. b. flask. in dry DMF (10 mL) under nitrogen atmosphere and with potassium carbonate (8.55 g, 61.9 mmol) at 70 °C for 1 h,
heated to 60 °C. Potassium carbonate (K2CO3) (0.72 g, then a solution of 1 (2 g, 5.16 mmol) in 5 mL dry DMF was
5.1 mmol) was added slowly followed by addition of KI (0.04 g, slowly added and the reaction mixture was heated under vigor-
0.28 mmol) and stirred for another 30 min at that temperature. ous stirring at 100 °C for 72 hours. The reaction mixture was
Then, a solution of P2 (1.0 g, 2.87 mmol) in dry DMF was cooled to room temperature and most of the solvent was
added slowly and the reaction continued at 100 °C for 36 h. removed under reduced pressure. Ice cold water was added
The reaction was quenched and the product was then precipi- and it was extracted with CH2Cl2, the organic part was repeat-
tated from cold methanol, washed and dried under high edly washed with ice cold water and it was then dried over
vacuum. FT-IR (KBr, cm−1): 704, 834, 1007, 1208, 1402, 1480, anhydrous MgSO4, solvent was removed to afford 2 (2.7 g,
1648, 2624, and 2920. 1H NMR (CDCl3): δ 1.45 (br, CHCH2 94%). Mp. above 200 °C. FT-IR (KBr, cm−1): 742, 1024, 1162,
1
polymer backbone), 1.82 (br, CHCH2 polymer backbone), 5.21 1202, 1452, 1481, 1722, and 2863. H NMR (CDCl3): δ 4.43 (s,
(br, –CH2O–(CHvCH2), polymer), 6.51 (br, –(CHvCH2), 8H), 6.98 (d, 8H, J = 8.6 Hz), 7.75 (d, 8H, J = 8.6 Hz), 9.79 (s,
polymer) 6.60 (br, Ar, polymer), 7.07 (br, Ar, polymer).
4H). 13C NMR (CDCl3): δ 31.2, 66.4, 114.8, 130.5, 131.9, 163.2,
190.6 (Fig. S4, ESI†). HRMS (ESI+) m/z: 553.1862 (calculated for
[M + H]+: 553.1859).
Preparation of oxime functionalized cross-linkers (Scheme 2)
Preparation of tetra-arm oxime (CL-1). Tetra-arm aldehyde 2
(0.3 g, 0.543 mmol) was dissolved in minimum volume
of ethanol, and hydroxylamine hydrochloride (NH2OH·HCl)
(0.226 g, 3.256 mmol) and sodium acetate (0.356 g,
4.344 mmol) were dissolved in minimum volume of water.
These two solutions were mixed and the reaction mixture was
stirred overnight at room temperature. After the removal of
ethanol, the reaction mixture was extracted with diethyl ether
and the combined organic layer was washed with water. The
ether portion was concentrated in a rotary evaporator under
reduced pressure. It was then dried to afford a pale yellow
solid CL-1 (0.32 g, 96%). FT-IR (KBr, cm−1): 1112, 1198, 1630,
1735, 2926, and 3425. 1H NMR (CDCl3): δ 4.27 (s, 8H), 6.95
Synthesis of pentaerythrityltetrabromide (1,3-dibromo-2,2-
bis-bromomethyl-propane) (1). Phosphorous tribromide (PBr3)
(22.3 mL, 235.2 mmol) in 100 mL dry diethyl ether was added
to a solution of pentaerythritol (2.0 g, 14.7 mmol) in 300 mL
dry diethyl ether at 0 °C for 15 min under a nitrogen atmos-
phere. After 1 hour, PBr3 (22.3 mL, 235.2 mmol) was added to
the mixture at 0 °C and then the reaction mixture was stirred
for 3 hours at room temperature. After that, the reaction
mixture was quenched with ice cold water and extracted with
diethyl ether and the organic layer was washed with aq.
NaHCO3 and dried over MgSO4. The crude product was
washed with cold ethanol and recrystallized from hot acetone.
Yield (2.4 g, 57%), mp: 158 °C. FT-IR (KBr, cm−1): 538, 830,
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(d, 8H, J = 8.0 Hz), 7.44 (d, 8H, J = 8.0 Hz), 7.99 (s, 4H), 10.9 (br THF and precipitated from cold hexane and dried under high
1
s, 4H). 13C NMR (CDCl3): δ 31.1, 66.3, 114.9, 126.0, 127.8, vacuum. Formation of isoxazoline was confirmed by H NMR
147.6, 159.3 (Fig. S5, ESI†). HRMS (ESI+) m/z: 613.2298 (calcu- analysis. 1H NMR (CDCl3): δ 1.46 (br, CHCH2 polymer
lated for [M + H]+: 613.2165).
backbone), 1.88 (br, CHCH2 polymer backbone), 4.2
Preparation of terephthaldialdehyde oxime (CL-2). Tere- (br, –CCSH2CH-isoxazoline), 5.3 (br, –CHO-(isooxazoline),
phthaldialdehyde (1.374 g, 10 mmol) was mixed with 5 mL of polymer), 5.3 (br, –CH2OCOCHvCH2, polymer), 6.6 (br, Ar,
THF and NH2OH·HCl (1.146 g, 15.0 mmol). Sodium acetate polymer), 7.1 (br, Ar, polymer).
(1.67 g, 20.0 mmol) was dissolved in minimum vol. of water.
These two solutions were mixed and the reaction mixture was
stirred overnight at room temperature. After removal of THF it
was extracted with ether. The ether extracts were combined
Results and discussion
and washed with water. The organic part was concentrated in
a rotary evaporator under reduced pressure. It was then dried
In this work, we have established a new method for the syn-
thesis of core cross-linked star (CCS) polymers via the for-
mation of an isoxazoline ring resulting from 1,3-dipolar
to provide terephthaldialdehyde oxime i.e. CL-2 as a pale
yellow solid (1.45 g, 93%). FT-IR (KBr, cm−1): 838, 1182, 1632,
cycloaddition reaction between vinyl groups of the acrylate
1
1730, 2898, 3440. H NMR (DMSO-d6): δ 11.3 (s, 2H), 8.14 (s,
functionalities in the polymer chain and nitrile-oxide groups
2H), 7.61 (s, 4H). HRMS (ESI+) m/z: 165.0664 (calculated for
formed in situ from oxime-functionalized cross-linking agents.
[M + H]+: 165.0459).
The alkene-nitrile oxide cyclo-addition reaction is known in
Synthesis of CCS-polymer from P2a and CL-1. CCS polymers
were synthesized by reacting P2a with CL-1. In a typical reac-
tion (exp no. 3, Table 2) CL-1 (0.053 g, 0.0869 mmol) was dis-
solved in 5 mL of dry DCM under a nitrogen atmosphere
followed by addition of iodosobenzenediacetate (0.70 g,
the literature.14,19 In this work we have extended this concept
to a polymeric system in order to produce well-defined star
architecture.
Synthesis of the block copolymers
2.17 mmol) and MgSO4 (0.3 g, 2.17 mmol) into it at 0 °C for
10 min. P2a (0.5 g, ∼0.434 mmol) in 10 mL of dry DCM was
added slowly for 15 min at 0 °C and the reaction mixture was
stirred overnight at room temperature. Unreacted MgSO4 was
removed by filtration and the polymer was isolated by precipi-
tation from an ice-cold hexane–methanol mixture dried under
high vacuum. Formation of isoxazoline was confirmed by 1H
NMR analysis. 1H NMR (CDCl3): δ 1.45 (br, CHCH2 polymer
backbone), 1.84 (br, CHCH2 polymer backbone), 4.1 (br,
The block copolymer was synthesized by RAFT technique
using α,α′-xylyl-bis(dithiobenzoate) as a chain transfer agent
(CTA), as depicted in Scheme 1. 4-Vinyl benzylchloride was
initially polymerized to yield poly(4-vinyl benzylchloride)
macro-CTA (P1) of Mn ∼ 5800 and PDI ∼ 1.10 (Table 1), which
was further utilized for the controlled polymerization of
styrene to form block copolymer P2 having Mn ∼ 13 400 and
PDI ∼ 1.21 (Table 1). The controlled and living nature of the
RAFT polymerizations were confirmed from molecular weight
vs. % conversion plot (see ESI, Fig. S6†). Thereafter, P2 was
reacted with acrylic acid in dry DMF with K2CO3 and KI to give
the corresponding acrylate derivative P2a, with Mn ∼ 14 100
and PDI ∼ 1.36 (Table 1). The incorporation of the acrylate
function in the polymer chain was confirmed from 1H NMR
analysis as shown in Fig. 1. The deshielded nature of the
benzyl protons due to incorporation of acrylate moiety in the
polymer chain was evident from the appearance of a peak at
5.1 ppm. In addition, the appearance of broad peaks at
5.6 ppm and 6.1 ppm due to vinylic protons confirmed suc-
cessful incorporation of the acrylate moiety in the polymer
segment. However, the existence of peaks at 4.6 ppm corres-
ponding to benzylic protons of 4-vinylbenzyl chloride eluci-
dated that the acrylation reaction was not quantitative
–CCSH2CH-isoxazoline),
5.1
(br,
–CHO-(isooxazoline),
polymer), 5.1 (br, –CH2OCOCHvCH2, polymer), 6.52 (br, Ar,
polymer), 7.1 (br, Ar, polymer).
Synthesis of CCS-polymer from P2a and CL-2. In another
approach, CCS polymers were synthesized by reacting P2a with
CL-2. For example (exp no. 3, Table 2), terephthaldialdehyde
oxime (CL-2) (0.014 g, 0.0869 mmol) in 5 mL dry DCM was
taken in a r. b. flask under nitrogen atmosphere with continu-
ous stirring. Iodosobenzenediacetate (0.70 g, 2.17 mmol) and
MgSO4 (0.3 g, 2.17 mmol) were added into this solution at 0 °C
with vigorous stirring for 10 min. P2a (0.5 g, ∼0.434 mmol) in
5 mL of dry DCM was added slowly for 15 min at 0 °C and the
post reaction mixture was stirred overnight at room tempera-
ture. Unreacted MgSO4 was removed and the solvent was evap-
orated under reduced pressure. It was then dissolved in 3 mL
Table 1 Characterization of the linear polymers
Polymer
CTA agent
Monomer
Initiator
Temp (°C)
Time (h)
Mna (g mol−1
)
Mnb (g mol−1
)
PDIb
P1
P2
P2a
XBDTB
P1 macro-CTA
4-Vinyl benzyl chloride
Styrene
AIBN
AIBN
80
80
20
24
5400
11 500
13 900
5800
13 400
14 100
1.10
1.21
1.36
a From 1H NMR. b From GPC; solvent for polymerization medium – 1,4-dioxane.
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Fig. 1 1H NMR spectra of acrylate functionalized polymer P2a.
(conversion ∼40%) which may be due to the poor nucleophilic 1H NMR spectroscopy and the spectra are provided in ESI
nature of the acrylate ion.
(Fig. S3 to Fig. S5†).
Synthesis of cross-linkers
Synthesis of the core cross-linked star (CCS) polymers
The cross-linking agents used in this work have been syn-
thesized in the laboratory as described in Scheme 2. Pentaery- The block copolymer P2a was reacted with both the CL-l and
thrityl tetrabromide was reacted with p-hydroxy benzaldehyde CL-2 to form the core cross-linked star (CCS) polymers through
to form the four-arm aldehyde functionalized molecule and isoxazoline formation as a result of alkene-nitrile oxides cyclo-
the purified product was further reacted with NH2OH·HCl/ addition reaction (‘click reaction’), as depicted schematically
NaOAc yielding the corresponding oxime derivative that was in Fig. 2. In the first step towards the formation of CCS poly-
used as the tetra-arm cross-linker (CL-1). The bifunctional mers, CL-l and CL-2 were reacted with PhI(OAc)2 in dry DCM
oxime of terephthaldialdehyde (CL-2) was synthesized from followed by reaction of the intermediate with vinyl groups of
terephthaldialdehyde. The cross-linkers were characterized by the block copolymer P2a.
Fig. 2 Schematic representation of formation of core cross-linked polymers through isoxazoline ring formation from P2a and CL-1.
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Fig. 3 1H NMR spectra of CCS polymer produced from P2a with CL-1.
Characterization of the CCS polymers
The cross-linking reactions were carried out at different mole
ratios of the cross-linker(s) and the block copolymer. No gela-
tion was observed in the experiments in the concentration
range of cross-linkers (5–20 mol%) used in this study. The
resulting star-branched polymers were completely soluble in
the common organic solvents like THF and DMSO. The poly-
styrene blocks on either side of the reactive middle block that
forms the arms of the star-branched polymers probably help to
solubilize the core cross-linked star polymers. The formation
of targeted CCS polymers was confirmed by 1H NMR, FTIR,
GPC, and DLS analysis.
1H NMR and FTIR analysis. Fig. 3 represents 1H NMR
spectra of the polymer formed by reaction with P2a and Fig. 4 FT-IR spectra of CL-1, polymer P2a and CCS polymer from one
20 mol% of cross-linker, CL-1. On comparison of this 1H NMR
of P2a and CL-1 (exp. no. 3 in Table 2).
spectra with the spectra of P2a (Fig. 1), it was noted that the
peaks at 5.6 ppm and 6.1 ppm corresponding to the vinylic
protons of P2a, have completely disappeared (Fig. 3) in the
cross-linker polymer and a new peak around 4.1 ppm appeared
due to two diastereotopic protons of the newly formed isoxazo-
GPC and DLS study. GPC elugrams of the CCS polymers
(exp. nos 2, 3, 5, 6; Table 2) along with those of the starting
linear block copolymer (P2a) are shown in Fig. 5. GPC analysis
of the CCS polymers showed the elugrams corresponding to
the CCS polymers appeared at significantly lower elution
volumes compared to the starting linear block copolymer
suggesting a significant increase in molecular weights of the
product over the starting linear block copolymers. This also
implies the possible formation of the desired CCS polymers by
linking of multiple linear chains through cross-linking via an
alkene-nitrile oxide ‘click reaction’ between the reactive middle
blocks and the cross-linkers. Moreover, no peak corresponding
to the starting linear block copolymer was observed indicating
complete incorporation of the starting block copolymer in the
cross-linked structure. The molecular weight data are provided
in Table 2. For example, the Mn of the starting linear block
1
line ring (relevant peaks are encircled in the H NMR spectra,
Fig. 1 and 3). Complete disappearance of the peaks corres-
ponding to the vinylic protons indicated that the ‘click reac-
tion’ proceeded in a quantitative manner. The disappearance
of the FT-IR peak at ∼3470 cm−1 corresponding to O–H of
oxime (Fig. 4) and appearance of a new peak at 1180 cm−1
corresponding to N–O also suggest the formation of the
isoxazoline ring. The formation of the isoxazoline ring in
the polymer system was further confirmed by a model
reaction between the acrylate derivatives synthesized from P1
with the oxime of anisaldehyde. The isoxazoline ring in the
polymer system was confirmed by 1H and 13C-NMR (see the
ESI†).
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Table 2 Characterization of CCS polymers
Conc. of block
copolymer in
terms of acrylate
groups (mmol)
mol% of
cross-linker
(w.r.t. acrylate
groups)
Approx. no.
of arms per
CCSb
a
Exp.
no.
Cross-
linker
Mn
Hydrodynamic
(g mol−1
)
PDI
radius (Rh)c
1
2
3
4
5
6
CL-1
CL-1
CL-1
CL-2
CL-2
CL-2
0.434
0.434
0.434
0.434
0.434
0.434
5
10
20
5
10
20
79 900
111 700
261 000
23 500
34 600
48 500
1.54
1.40
1.70
1.27
1.60
1.37
12
18
36
4
6
8
11.5
23.0
57.8
9.8
20.3
26.3
a From GPC. b (Mn of CCS)2/(Mn of P2a). c From DLS.
mentioning that the approximate number of arms in the CCS
polymers have been calculated by dividing the final molecular
weight of the CCS polymer by that of the starting block copoly-
mer and multiplying the result by two to account for two poly-
styrene arms per linear block copolymer. The contribution to
molecular weights by the cross-linkers has been ignored in
this calculation for the convenience of the calculation.
The cross-linking reactions were also carried out using
different mole ratios of the cross-linker(s) to the block copoly-
mer, where the concentration of the cross-linker(s) were varied
keeping the concentration of the polymer P2a fixed. It was
observed that the molecular weight of the CCS polymers were
steadily increasing with increase in the concentration of the
cross-linkers, indicating the incorporation of more linear
chains to a single core. The molecular weight data clearly
suggested that the four-arm cross-linker was more efficient for
the formation of the core cross-linked polymer. The formation
of the core cross-linked polymers was further investigated by a
dynamic light scattering (DLS) study as shown in Fig. 6. The
hydrodynamic size values are presented in Table 2. The hydro-
dynamic size (Rh) of the block copolymer P2a was found to be
Fig. 5 GPC traces of (top) polymer P1, P2 and exp. nos 2 & 3 of Table 2,
and (bottom) polymer P1, P2 and exp. nos 5 & 6 of Table 2 in THF
(1.0 mL min−1).
copolymer (P2a) was ∼14 100 which, on cross-linking with
CL-1 (exp no. 2, Table 2), yielded a CCS polymer with Mn
111 700 that corresponds to a cross-linked polymer having
approximately eighteen polystyrene arms. It is worth
∼
Fig. 6 DLS data of the block copolymer P2a and the CCS polymers.
Sample details of exp. no. 1 to exp. no. 6 along with the hydrodynamic
size can be found in Table 2.
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∼7 nm. The hydrodynamic sizes of the CCS polymers were
found to increase significantly. For example, an increase of
hydrodynamic radius from ∼7 nm for the block copolymer P2a
in THF to 58 nm and 26 nm was observed for the CCS poly-
mers with 20 mol% of CL-1 and CL-2, respectively. A similar
change in hydrodynamic radius due to the formation of core
cross-linked networks was also observed by Sumerlin et al.,8
Fulton et al.,9 Stenzel et al.,20 Lee et al.21 Also, a larger hydro-
dynamic radius was observed in the case of CL-1 compared to
CL-2 at the same concentration (mol%) which relates to a
more effective cross-linking leading to higher incorporation of
arms by CL-1, which correlates with molecular weight data as
discussed earlier. Although it is a fact that a more precise
characterization of these synthesized star-branched polymers
is possible by using a multi-angle light scattering detector, yet
our results based on 1H NMR, FTIR, GPC and DLS grossly hint
to the formation of core cross-linked star polymers via the for-
mation of an isoxazoline ring using ‘click chemistry’.
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Conclusion
In conclusion, this study may be envisaged as an effort to in-
troduce a green methodology for the synthesis of CCS polymers
through isoxazoline ring formation in a rapid, convenient, one-
pot nitrile oxide-acrylate 1,3-DC reaction. Unlike conventional
Cu-catalyzed reactions that are associated with the risk of con-
tamination by the metal beyond threshold level, rendering them
particularly unfavorable for biological applications, this process
does not require the use of Cu, thus ensuring the development
of a hazardless product. The synthesis of acrylate functionalized
triblock copolymers of well-defined structures were made possi-
ble by the versatile RAFT technique. A reasonably good control
on the molecular weight and PDI of the linear block copolymer
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allowed the formation of
a well-defined CCS polymer.
Such advanced technologies based on metal-free chemistry are
of utmost significance, as they may be effectively applied for
developing new materials for diverse applications, particularly
in the field of biological sciences.
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Acknowledgements
Financial support from the Department of Science and Tech-
nology, Government of India, New Delhi, (Project ref. no. SR/
FTP/CS-79/2007) is acknowledged. R. Banerjee and S. Maiti
acknowledge UGC and CSIR, New Delhi, respectively, for
Research Fellowships. The authors are also thankful to Prof.
Nilmoni Sarkar for providing help in DLS measurements.
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