Thiol-ene clickable hyperscaffolds bearing peripheral allyl groups

Article abstract of DOI:10.1002/pola.24597

Radical catalyzed thiol-ene reaction has become a useful alternative to the Huisgen-type click reaction as it helps to expand the variability in reaction conditions as well as the range of clickable entities. Thus, direct generation of hyperbranched polymers bearing peripheral allyl groups that could be clicked using a variety of functional thiols would be of immense value. A specifically designed AB₂ type monomer, that carries two allyl benzyl ethers groups and one alcohol functionality, was shown to undergo self-condensation under acid-catalyzed melt-transetherification to yield a hyperbranched polyether that carries numerous allyl end-groups. Importantly, it was shown that the kinetics of polymerization is not dramatically affected by the change of the ether unit from previously studied methyl benzyl ether to an allyl benzyl ether. The peripheral allyl groups were readily clicked quantitatively, using a variety of thiols, to generate an hydrocarbon-soluble octadecyl-derivative, amphiphilic systems using 2-mercaptoethanol and chiral amino acid (N-benzoyl cystine) derivatized hyperbranched structures; thus demonstrating the versatility of this novel class of clickable hyperscaffolds.

Full text of DOI:10.1002/pola.24597

Thiol-ene Clickable Hyperscaffolds Bearing Peripheral Allyl Groups
RAJ KUMAR ROY, S. RAMAKRISHNAN
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India
Received 27 December 2010; accepted 18 January 2011
DOI: 10.1002/pola.24597
Published online 1 March 2011 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: Radical catalyzed thiol-ene reaction has become a
useful alternative to the Huisgen-type click reaction as it helps
to expand the variability in reaction conditions as well as the
range of clickable entities. Thus, direct generation of hyper-
branched polymers bearing peripheral allyl groups that could
be clicked using a variety of functional thiols would be of
immense value. A specifically designed AB2 type monomer,
that carries two allyl benzyl ethers groups and one alcohol
functionality, was shown to undergo self-condensation under
acid-catalyzed melt-transetherification to yield a hyperbranched
polyether that carries numerous allyl end-groups. Importantly,
it was shown that the kinetics of polymerization is not dramati-
cally affected by the change of the ether unit from previously
studied methyl benzyl ether to an allyl benzyl ether. The
peripheral allyl groups were readily clicked quantitatively,
using a variety of thiols, to generate an hydrocarbon-soluble
octadecyl-derivative, amphiphilic systems using 2-mercaptoeth-
anol and chiral amino acid (N-benzoyl cystine) derivatized
hyperbranched structures; thus demonstrating the versatility of
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V
this novel class of clickable hyperscaffolds.
2011 Wiley
Periodicals, Inc. J Polym Sci Part A: Polym Chem 49:1735–
1744, 2011
KEYWORDS: functionalization of polymers; glass transition;
hyperbranched; kinetics (polym.); polyethers; thermogravimet-
ric analysis (TGA)
INTRODUCTION Hyperbranched polymers, prepared via the
self-condensation of an AB2 type monomer, yields polymers
with large number of B groups at the periphery.1 The
numerous end-groups present in hyperbranched polymers
make them potentially useful as crosslinkers, scaffolds for
preparing core-shell type polymers, and so forth. Typically,
the end-groups in hyperbranched polymers which are readily
amenable to further functionalization are amines, alcohols or
carboxylic acids. These functional groups can be modified
under standard conditions to generate a wide range of
peripherally functionalized polymers, although it is often dif-
ficult to achieve high conversions.2 A few years ago, we dem-
onstrated an alternate straightforward approach that utilized
the copolymerization of an AB2 monomer with a A-R type
molecule to generate peripherally modified hyperbanched
systems in a single step; however, this approach also had the
limitation of incomplete conversion.3 Despite these limita-
tions, peripherally functionalized hyperbranched polymers,
such as hyperbranched polyglycerols, have been extensively
explored to yield a variety of interesting structures.4
that carries two propargylbenzyl ether groups and one
hydroxyl group; acid-catalyzed melt-transetherification of
this monomer yielded a hyperbranched polymer bearing a
large number of peripheral propargyl groups, which could in
turn be quantitatively functionalized under mild conditions
via the Cu-catalyzed click reaction with a variety of organic
azides.5 Later we also showed that hyperbranched polyesters
can be similarly prepared under standard melt transesterifi-
cation process of a suitably designed hydroxy bis(propargyl
ester) monomer.6 This was an important finding because it
demonstrated for the first time that propargyl ester groups
can be trans-esterified just like any other simple methyl or
ethyl esters, which are typically the basic monomers for
commercial production of polyesters. Although alkyne-azide
click reactions have their own merits, search for alternate
reactions that proceed quantitatively under mild conditions
has lead to the identification of several other potentially use-
ful approaches; of these the most extensively studied is the
thiol-ene reaction.7 The thiol-ene reaction, which is the cen-
tury-old radical-catalyzed addition of a thiol to an alkene,
exhibits several of the important characteristics to qualify
being termed a click reaction, as delineated by Sharpless;8
the reactions occur quantitatively under very mild condi-
tions, generates no side products and, importantly, it can be
carried out under biologically benign conditions. Some of the
advantages of the thiol-ene reaction over the Cu-catalyzed
1,3-dipolar cycloaddition based click reaction is that it can
We have been interested in developing simple and straight-
forward approaches for the preparation of hyperbranched
polymers that carry quantitatively functionalizable end-
groups. To this end, we recently developed a novel strategy
to prepare peripherally ‘‘clickable’’ hyperbranched polyethers
in a single step using a suitably designed AB2 type monomer
Additional Supporting Information may be found in the online version of this article. Correspondence to: S. Ramakrishnan (E-mail: raman@ipc.iisc.
ernet.in)
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Journal of Polymer Science Part A: Polymer Chemistry, Vol. 49, 1735–1744 (2011) 2011 Wiley Periodicals, Inc.
HYPERSCAFFOLDS BEARING PERIPHERAL ALLYL GROUPS, ROY AND RAMAKRISHNAN
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the preparation of clickable hyperbranched polyethers from
an AB2 type monomer and demonstrate that these polymers
can be readily transformed to interesting functional systems
by clicking with different thiols, thereby making them poten-
tially useful as nano-dimensional hyperscaffolds for a variety
of applications.
RESULTS AND DISCUSSION
Some years ago, we developed an interesting melt trans-
etherification polymerization process wherein a monomer
carrying two benzylmethyl ether groups when reacted with
ꢀ
an aliphatic diol at 150 C in the presence of an acid catalyst,
like PTSA, yielded a polyether with the exclusion of low boil-
ing methanol.12 This process was later optimized and
extended for the preparation of hyperbranched polyethers
using a suitably designed AB2 monomer (A) (Scheme 1),
which in turn was prepared from Mesitol.13 Recently we
showed that, if instead of the benzylmethyl ether a benzyl-
propargyl ether were used, a hyperbranched polyether bear-
ing numerous terminal propargyl groups was formed.5 Click
reaction of the propargyl groups with a variety of organic
azides permitted the generation of a variety of peripherally
funtionalized hyperbranched polymers. As the thiol-ene click
reaction often complements the alkyne-azide process, we
designed alternate AB2 monomer (3) bearing two benzylallyl
ethers and one hydroxyl group, which can undergo a similar
transetherification polycondensation. The monomer was pre-
pared starting from Mesitol in three steps as depicted in
Scheme 2. A fully substituted aromatic nucleus is used to
preclude electrophilic aromatic substitution that could occur
during the acid-catalyzed melt condensation.12 Melt polymer-
ization of this monomer in the presence of 2 mol % of pyri-
dinium camphor sulphonate (PCS)13(b) proceeded smoothly
at 150 ꢀC with rapid evolution of allyl alcohol. The
SCHEME 1 Synthesis of hyperbranched polyether with
methoxy endgroups.
be done in the absence of a metal ion and can also be initi-
ated photochemically in the absence of any radical initiator.9
Given the merits of the thiol-ene reaction and its wide rang-
ing application potential, it would be useful to develop sim-
ple strategies to synthesize hyperbranched polymers that
carry numerous peripheral allyl groups, in a single step. Den-
drimers carrying numerous allyl groups at their periphery
have been synthesized and utilized to access a wide range of
structures using the thiol-ene click process.10 While den-
drimers provide structurally perfect scaffolds for building
variety of interesting nano-dimensional systems, they require
tedious step-wise synthesis; a notable recent exception is the
use of the thiol-ene reaction itself for the construction of the
dendrimer, which has simplified the procedure consider-
ably.11 In this article, we describe a single-step process for
SCHEME 2 Synthesis and polymerization of the bis-allyloxy AB2 monomer.
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SCHEME 3 Thiol-ene click reaction of the allyl-terminated HBP with a variety of thiols.
polymerization was done in two steps—in the first step a
slow purge of dry nitrogen was used to remove the allyl
alcohol that was formed and the second step was done
under reduced pressure to drive the reaction to completion.
ular weight of the polymer was determined using GPC, which
was coupled to a triple detector systems and the Mw was
estimated to be around 15,000 (PDI ¼ 2.3) based on the
Universal calibration method.
The proton NMR spectra of the monomer 3 and the hyper-
branched polymer (HBP-Allyl) are shown in Figure 1, along
with the peak assignments. The main difference in the spec-
tra is the decrease in the relative intensity of the peaks
belonging to the allyl unit; the ratio of the allyl methylene
protons (peak d) to the benzylic protons (peak c and c’)
changes from 1:1 to nearly 0.5:1, which is expected at high
conversions. Unlike in the HBP-Me polymer (see Scheme
1),14 in the allyl polymer the benzylic proton peaks do not
resolve adequately to permit the direct determination of the
degree of branching (DB). However, using previously estab-
lished spectral assignment of the aromatic methyl protons
(the seven peaks in the region 2.2–2.5 ppm),14 the DB was
estimated to be around 0.45, which is in reasonable accord-
ance with the statistically expected value of 0.5.15 The molec-
Kinetics of Polymerization
The rate of the transetherification process would expectedly
depend on ether linkage that is being cleaved, both because
of the difference in intrinsic susceptibility of the ether link-
age as well as due to the difference in volatility of the liber-
ated alcohol; the removal of which drives the equilibrium
towards polymer formation. To study the rate of polyconden-
sation, we chose to directly use thermogravimetric analysis
(TGA); because the volatility of the monomer at the polymer-
ization temperature of 150 ꢀC was small, the weight loss
during the analysis may be ascribed primarily to the loss of
the condensate alcohol alone. TGA has been very seldom
used to follow the kinetics of polycondensation and, to the
best of our knowledge, there is only one report that has
done so,16 even though it is evident that TGA would be one
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FIGURE 1 1H NMR spectra of monomer 3 and the hyperbranched polymer; the spectrum of the polymer was recorded in C6D6 to
provide improved spectral resolution. Peaks marked by an * are due to either solvent or inadvertent water contamination. [Color
figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
of the quickest ways to obtain kinetic information and,
importantly, it would require only very little sample. To
obtain meaningful data from the TGA runs, however, one
needs to ensure that the purge rate of the career gas is
adequate to rapidly carry the volatile condensate; this will
ensure that the weight loss is indeed a direct reflection of
the condensation rate.
150 ꢀC; the temperature was then held constant and the
weight-loss was monitored as a function of time. The first
isothermal segment (3 mins at 100 ꢀC) was to ensure that
Firstly, to gain a quick estimate of the relative of the rates of
polymerization, the TGA thermograms of both the mono-
mers, namely the bis-allyl ether monomer (3) and the bis-
methyl ether monomer (A), were carried out under a fixed
nitrogen purge rate 20 mL/min in the presence of 2 mol %
of the catalyst, pyridinium camphorsulfonate, PCS (Support-
ing Information Fig. S2). At first sight, it appeared that the
weight-loss in the case of monomer 3 begins at a slightly
lower temperature suggesting greater ease of polymerization
in this case. However, careful examination revealed that the
difference is more a reflection of the higher molecular
weight of the evolved fragment in the case of the allyl ether
monomer. Additionally, it was also noticed that a gradual
weight loss began right from the beginning of the run sug-
gesting the presence of some volatile species, like a solvent.
FIGURE 2 Isothermal TGA scans of the two monomers, in the
presence of 2 mol % PCS at 150 ꢀC; Inset shows a plot of
percent conversion versus time for the two monomers. The
plateau value of the weight loss for the two monomers (mono-
mer A-red and 3-black) are different reflecting the loss of
higher molecular weight, allyl alcohol, in case of monomer 3.
In an effort to gain a more quantitative assessment of the
relative rates of polycondensation, we carried out isothermal
TGA experiments. Here the monomer with the required
amount of PCS was heated rapidly to 100 ꢀC, held at this
temperature for 3 min and then heated at 10 deg/min to
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FIGURE 3 Stack plot of the 1H NMR spectra of aliquots taken after different time intervals during the polymerization of monomer
3. The polymerization times are listed on the right, while the numbers on top of the peaks reflect their relative intensities; the set
of peaks between 2.2 and 2.5 ppm have been normalized in all the spectra to reflect 9 protons.
any weight loss due to the inadvertent presence of volatiles
is accounted for and, secondly, this permitted the heating to
150 C to be carried out in a relatively short time before be-
percent weight loss in each case, shows that the two mono-
mers appear to polymerize at roughly similar rates (see
Fig. 2 inset); this is evident from the near overlapping of the
two curves and the similar slopes exhibited for the linear
segment after the apparent induction period. This study con-
firms that replacing the methyl groups in monomer A with
allyl groups does not change the rate of polycondensation
significantly.
ꢀ
ginning the isothermal segment. This ensured that minimum
weight loss (due to condensation) occurs during the temper-
ature ramp segment. The flow rate of the purge gas was
maintained at 20 mL/min to ensure that the weight loss
does reflect the rate of polycondensation. Figure 2 shows the
isothermal scans of the two monomers; here again the rela-
tive slopes appear to suggest that polymerization of the allyl
monomer 3 may be faster. However, further analysis of the
data, wherein the percent conversion is estimated from the
A similar kinetics study was carried out by taking aliquots
from the polymerization mixture after different time inter-
vals and recording their NMR spectrum. A stack plot
HYPERSCAFFOLDS BEARING PERIPHERAL ALLYL GROUPS, ROY AND RAMAKRISHNAN
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showing the spectral evolution as a function of polymeriza-
tion time is shown in Figure 3. The intensity of an invariant
set of peaks, such as those due to the three aromatic methyl
groups at 2.3–2.4 ppm, was normalized to reflect nine pro-
tons; this permitted the direct comparison of the peaks due
to the allyl unit (for instance, the peak at 5.3 ppm), as indic-
ative of the percent conversion. The intensity of this peak (at
5.3 ppm) clearly decreases with polymerization time; the
percent conversion can be readily estimated from this varia-
tion in relative intensities, and the values thus obtained are
plotted as a function of polymerization time in Figure 4.
Here again, the comparison of the initial polymerization rates
(up to 40 min, after which the polymerization is carried out
under a reduced pressure of 2 torr) of monomers 3 and A
suggests that the rates are not significantly different;
although the allyl monomer appears to polymerize margin-
ally faster.
increased slightly, except in the case of 2-mercaptoethanol
where a small apparent reduction was noticed; this we
believe is more a reflection of chain compaction due to intra-
molecular H-bonding (see Supporting Information).
Thermal Properties of Clicked Hyperbranched Polymers
It is well-known that the thermal properties of hyper-
branched polymers depend strongly on the nature of termi-
nal groups.17 The DSC thermograms of the various clicked
polymer samples along with that of the pristine hyper-
branched polyether (HBP-allyl) are shown in Figure 6. All
the hyperbranched polymers, except HBP-SC18 that carries
long alkyl chains (C-18) at the periphery, are amorphous as
expected and exhibit only a glass transition. The Tg of the
ꢀ
parent polymer was at ꢁ13 C, while those clicked with ben-
zylthiol (HBꢀP-SBz) and 2-mercapto ethanol (HBP-SC2OH)
ꢀ
were at ꢁ4 C and ꢁ11 C, respectively. The very small dif-
ference between the parent polymer and HBP-SC2OH is a
bit surprising as one may have expected that the H-bonding
between the peripheral hydroxyl groups would increase the
Tg of the sample.
Overall, the NMR studies are broadly in concurrence with
the TGA analysis suggesting that simple TGA analysis could
serve as a quick and easy method for assessing the relative
polymerization rates of a variety of melt polymerizations,
especially when relatively nonvolatile monomers are used.
The Tg of the N-benzoyl cystine clicked polymer (HBP-NBC),
on the other hand, was significantly higher (57 ꢀC) reflect-
ing the presence of strong H-bonding interactions between
the pendant carboxylic acid groups as well as between the
amide units. Polymer HBP-NBC was also soluble in aqueous
bicarbonate solution due to the presence of numerous
pendant carboxylic acid groups. The octadecyl clicked poly-
mer HBP-SC18 was the only sample that was crystalline
and exhibited a clear melting transition around 33 ꢀC,
reflecting the strong tendency of the long paraffinic chains
to crystallize despite being present on a hyperbranched
core that contains a substantial number of linear defects.
Clicking the Hyperscaffold with Various Thiols
One of the virtues of generating hyperbranched polymers
that carry terminal allyl groups is the opportunity to gener-
ate a wide range of polymers with very distinct properties
by using different organic thiols. Of the various approaches
to carry out thiol-ene reactions, the photochemically initiated
approach, using 2,2-dimethoxy 2-phenyl acetophenone as the
initiator, is often the method of choice.9 Hence, in the present
studies, a solution of the hyperbranched polymer (HBP-allyl)
and the required thiol was taken along with the initiator in
THF and irradiated using a Hg-vapor lamp for about 4 h. The
isolated polymers were analyzed using 1H NMR and GPC.
Four different thiols were used for this study: benzyl thiol as
a control, octadecane thiol to induce hydrocarbon solubility,
2-mercaptoethanol to impart hydrophilicity and N-benzoyl
cystine to demonstrate the potential for bioconjugation; the
structures of these clicked hyperbranched polymers are
shown in Scheme 3.
The 1H NMR spectra of the homopolymer, along with those
of the clicked polymers are shown in Figure 5; the region
where the allyl proton signals is expected has been y-
expanded to reveal the absence of residual allyl groups in
the polymer, thereby confirming that the click reaction has
proceeded to near completion in all the cases. In addition to
the disappearance of the allyl proton signals, the relative
intensities of the signals arising from the clicked moiety
also tallies well with the expected values for quantitative
conversion. These experiments clearly suggest that the allyl-
terminated hyperbranched polyethers can indeed serve as
compact hyperscaffolds onto which a variety of function-per-
forming units could be ligated under fairly benign condi-
tions; this should make these polymers interesting and ame-
nable to facile anchoring of biologically interesting subunits.
The molecular weights of the clicked polymers typically
FIGURE 4 Plot of percent conversion of monomers 3 and A as
a function of polymerization time; the percent conversion was
estimated by 1H NMR spectroscopy. The first stage of polymer-
ization was carried out under dry N2 purge for 40 mins, after
which the polymerization was carried out under reduced pres-
sure (ꢂ2Torr). [Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.]
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FIGURE 5 1H NMR spectra of the pristine hyperbranched polymer (a), the polymer clicked with benzylthiol –HBP-SBz (b), with hex-
adecylthiol HBP-SC18 (c), with 2-mercaptoethanol HBP-S-C2-OH (d), and with N-benzoyl cystine HBP-NBC (e). The spectra of all
the polymers were recorded in CDCl3. Peaks marked by an * are due to either solvent or inadvertent water contamination. [Color
figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
This confirms the ability of the flexible core to adapt to
permit the crystallization of the peripheral alkyl groups; a
similar conclusion regarding the conformational adaptabil-
ity of the core was also inferred in the case of PEGylated
hyperbranched polymers that readily formed core-shell
type structures in aqueous solutions.3(a)
the kinetics of polymerization is not significantly altered
when the methyl benzyl ether groups in the AB2 monomer is
replaced by allyl benzyl ether groups. NMR structural studies
also confirm that the terminal allyl units can be quantita-
tively clicked using the thiol-ene reaction under photochemi-
cally initiated conditions. DSC studies clearly reveal the
strong influence of the nature on the terminal groups on the
Tg of hyperbanched polymers; the N-benzoyl cystine clicked
polymers exhibited a Tg about 70 degrees higher than the
parent polymer because of the strong H-bonding interactions
between the numerous terminal carboxylic acid groups.
When the HBP’s are clicked with long chain alkyl groups,
such as an octadecyl group, the polymer exhibits a clear
melting transition that reflects the very strong tendency of
long paraffinic chains to independently crystallize despite
their fairly irregular placement on a defective hyperbranched
framework indicating the adaptability of the relatively flexi-
ble core. Recent studies have revealed that diallylesters of 5-
CONCLUSIONS
We have demonstrated that the transetherification polycon-
densation is an effective strategy for the preparation of
hyperbranched polymers carrying numerous terminal allyl
groups. The polymerization proceeded by the self-condensa-
tion of an AB2 monomer that carries two allylbenzyl ether
groups and an aliphatic AOH group; the polymerization pro-
ceeds by the exclusion of one mole of allyl alcohol, while the
second mole of allyl groups decorates the periphery of the
hyperbranched polymer. TGA and NMR studies revealed that
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phenol (10 g, 73.5 mmol). The reaction mixture was refluxed
for 3 h, cooled to room temperature and poured into ice-
cold water. The residue was filtered through suction and
washed with saturated solution of NaHCO3 to ensure it is
acid free and then dried under vacuum (22.4 g, 95%, mp ¼
ꢀ
136 C).
1H NMR (d, ppm, CDCl3): 2.31 (s, 6H, Ar-CH3); 2.39 (s, 3H,
Ar-CH3); 4.57 (s, 4H, Ar-CH2Br).
3,5-Bis(allyloxymethyl)-2,4,6-trimethyl phenol (2)
Sodium metal (4.2 g, 182.6 mmol) was added in small pieces
to 150 mL of dry allyl alcohol. Compound 1 (10 g, 31 mmol)
was dissolved in allyl alcohol (ꢂ50 mL) and added drop-
wise to the degassed sodium alkoxide solution. The reaction
mixture was refluxed for 18 h under N2 atmosphere and
then cooled to room temperature. Excess allyl alcohol was
removed under reduced pressure and 100 mL of ice-cold
water was added to the residue, which was then acidified
using 10% HCl (v/v). The precipitate formed was extracted
with CHCl3 (2 ꢃ 100 mL) and the combined organic extract
was dried using anhydrous sodium sulphate. Chloroform was
removed under reduced pressure and the residue was dis-
tilled (220 ꢀC/2 Torr) in Kugelro¨hr apparatus (Yield ¼
33%).
FIGURE 6 DSC thermograms of the pristine HBP and the vari-
ous thiol-ene clicked derivatives. The studies were carried out
under a dry nitrogen purge at a heating rate of 5 deg/min.
Reproducibility of all the scan were checked by carrying out se-
quential heating-cooling-heating cycles and the reported scans
are the 2nd heating runs.
hydroxy-isophthalic acid also undergoes facile melt trans-
esterification polycondensation to yield similarly clickable
hyperbranched polyesters;18 this should make clickable
hyperbranched polymeric scaffolds more readily accessible,
given the ready availability of the starting material and sim-
plicity of the monomer synthesis. Presently, we are exploring
various applications of such clickable HBP’s that involve
simultaneous, and often orthogonal, clicking of multiple units
on to a single scaffold for introduction of multiple functions.
1H NMR (d, ppm, CDCl3): 2.27 (s, 6H, Ar-CH3); 2.36 (s, 3H,
Ar-CH3); 4.04 (d, 4H, Ar-OCH2CHCH2); 4.52 (s, 4H, Ar-CH2O-);
4.60 (s, 1H, Ar-OH); 5.25 (m, 4H, ArOCH2CHCH2); 5.97 (m, 2H,
ArOCH2CHCH2).
4-Bromobutylacetate (3)20
2.16 g (26.0 mmol) 1,2-dibromoethane was added to 0.63 g
(26 mmol) of Mg turnings in 25 mL of dry ether under N2
atmosphere and the mixture was stirred for 3 h at RT until
evolution ethylene gas ceases, suggesting complete formation
of MgBr2. The excess ether was removed under reduced
pressure and 25 mL of dry acetonitrile was added to the
solid mass followed by addition of 2.05 mL of dry THF and
5.20 mL of acetic anhydride. The mixture was stirred for 16
h at room temperature, neutralized with NaHCO3 solution
and then extracted with (3 ꢃ 50 mL) of diethyl ether. The
ether layer was dried over anhydrous Na2SO4, concentrated
and distilled in a Kugelro¨hr (87 ꢀC/2.0) torr to get desired
product (Yield ¼ 90%).
EXPERIMENTAL
Materials and Methods
2,4,6-Trimethyl phenol, octadecanthiol, 2-mecaptoethanol, tri-
oxane and camphor sulfonic acid were purchased from
Sigma-Aldrich chemical company and used directly. Allyl
alcohol, metallic sodium, benzyl chloride, pyridine and 33%
acetic acid solution of HBr were purchased from Spectro-
chem and used directly. Common organic solvents were pur-
chased locally and distilled before use. 1H NMR spectrum
was recorded using a 400 MHz Bruker spectrometer using
CDCl3 as solvent, unless mentioned otherwise. DSC measure-
ments were carried out using a TA DSC-Q10 instrument. Gel
permeation chromatography (GPC) was carried out using a
Viscotek TDA model 300 system, which is coupled to refrac-
tive-index, differential viscometer and light scattering detec-
tors in series. The separation was achieved using two mixed-
bed PLgel columns (5 lm, mixed C) maintained at 35 ꢀC;
tetrahydrofuran (THF) was used as the eluent. The molecular
weights were estimated using a universal calibration curve
based on polystyrene standards.
1H NMR (d, ppm, CDCl3): 1.74-1.81 (m, 2H, -BrCH2CH2-);
1.88-1.95 (m, 2H, -CH2CH2OAc-); 2.03 (s, 3H, -OCOCH3); 3.42
(t, 3H, -CH2CH2Br); 4.07 (t, 2H, -CH2CH2OAc).
1-(4-Hydroxybutyloxy)-3,5-bis(allyloxymethyl)-2,4,
6-trimethylbenzene (4)
A mixture of K2CO3 (15 g, 108.6 mmol) and catalytic amount
of KI were taken in dry acetonitrile (120 mL). The mixture
was degassed for 20 min by purging with nitrogen after
which 3 (5.3 g, 27.17 mmol) and 2 (5.0 g, 18.1 mmol) were
added to the solution. The reaction mixture was degassed
for further 20 min and then refluxed for 72 h under N2
atmosphere. The solvent was them removed under reduced
pressure and 50 mL of ice-cold water was added to it. The
resulting solution was extracted with 150 mL (2 ꢃ 75 mL)
3,5-Bisbromomethyl-2,4,6-trimethylphenol (1)19
One-hundred milliliter of HBr in AcOH (33%) was added to
a mixture of trioxane (6.61 g, 73.5 mmol) and 2,4,6-trimethyl
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diethyl ether; the ether layer was washed with 120 mL (4 ꢃ
30 mL) 10% aq. NaOH solution followed by water (30 mL)
and brine solution (30 mL). The ether layer was dried over
anhydrous sodium sulphate and concentrated under reduced
pressure. The acetate derivative (without any further purifi-
cation) along with 50 mL of 10% aq. NaOH and equal
amount of ethanol were refluxed overnight and cooled to RT.
The product was extracted into diethyl ether (2 ꢃ 50 mL),
dried over anhydrous Na2SO4, and concentrated. The crude
product was purified on a silica-gel column using ethyl ace-
tate-Pet. ether (35:65 v/v) as the eluent. (Yield ¼ 60%).
CH2CH2OH); 3.62 (t, 2H, ArCH2OCH2CH2CH2SCH2Ph);
3.67 (s, 2H, ArSCH2Ph); 4.49 (m, 4H, Ar-CH2O-); 7.25 (m,
5H, -SCH2Ph)
Clicking with all other thiols, namely 2-mercaptoethanol, 1-
octadecane thiol and N-benzoyl cystine, were carried out
using a similar procedure to give -HBP-SC2OH, HBP-SC18
and HBP-NBC, respectively, in yields ranging from 60 to
70%, after two reprecipitations.
HBP-SC2OH
1H NMR (d, ppm, CDCl3): 1.85 (m, 6H, ArOCH2CH2CH2-
CH2OH, ArCH2OCH2CH2CH2S-); 2.25-2.38 (m, 9H, Ar-CH3);
2.59 (t, 2H, -ArCH2CH2SCH2CH2OH); 2.65 (t, 2H, -ArCH2-
SCH2CH2OH); 3.59-3.64 (m, 8H, ArOCH2CH2CH2CH2OH,
ArCH2OCH2-, ArSCH2CH2OH); 4.49 (m, 4H, Ar-CH2O-).
1H NMR (d, ppm, CDCl3): 1.81 (m, 2H, ArOCH2CH2CH2-
CH2OH); 1.90 (m, 2H, ArOCH2CH2CH2CH2OH); 2.30 (s, 6H,
Ar-CH3); 2.36 (s, 3H, Ar-CH3); 3.68 (t, 2H, ArOCH2CH2CH2-
CH2OH); 3.74 (t, 2H, ArOCH2CH2CH2CH2OH); 4.05 (d, 4H,
Ar-CH2OCH2CHCH2); 4.51 (s, 4H, Ar-CH2O-); 5.25 (m, 4H,
ArCH2OCH2CHCH2); 5.97 (m, 2H, ArCH2OCH2CHCH2).
HBP-SC18
1H NMR (d, ppm, CDCl3): 0.88 (t, 3H, ArS(CH2)17CH3); 1.25-
1.60 (m, 32H, ArSCH2(CH2)16CH3); 1.85 (m, 6H, ArOCH2
CH2CH2CH2OH, ArOCH2CH2CH2S-); 2.25-2.38 (m, 9H, Ar-
CH3); 2.50 (t, 2H, ArSCH2(CH2)16CH3); 2.59 (t, 2H, -ArCH2
CH2SCH2(CH2)16CH3); 3.59-3.64 (m, 6H, ArOCH2CH2CH2
CH2OH, ArCH2OCH2-); 4.49 (m, 4H, Ar-CH2O-).
Polymerization
Monomer 4 (1.5 g, 4.31 mmol) along with 2 mol % of pyri-
dinium camphorsulfonate (PCS)13(b) was taken in a test-tube
shaped polymerization vessel. The mixture was degassed for
10 min and maintained at a temperature of 110 ꢀC under
continuous N2 purge, to ensure homogeneous mixing of cata-
lyst and monomers. The polymerization was then carried out
at 150 ꢀC under N2 for 1 h with constant stirring. Subse-
quently, using a Kugelro¨hr apparatus, the polymerization was
continued for an additional period of 45 min at 150 ꢀC
under reduced pressure (2 Torr), with continuous mixing of
the melt by rotation. The resultant polymer was dissolved in
THF, the acid-catalyst was neutralized with solid NaHCO3
and then the solution was filtered. The filtrate was concen-
trated under reduced pressure to a viscous solution and pre-
cipitated in methanol. The polymer was further purified
twice by dissolution in THF and reprecipitation into metha-
nol (Yield ¼ 70%).
HBP-NBC
1H NMR (d, ppm, CDCl3): 1.85 (m, 6H, ArOCH2CH2CH2-
CH2OH, ArOCH2CH2CH2S-); 2.25-2.38 (m, 9H, Ar-CH3); 2.59
(t, 2H, ArCH2CH2SCH2CH2OH); 3.59-3.64 (m, 8H, ArOCH2-
CH2CH2CH2OH, ArCH2OCH2-, ArSCH2CH(CO2H)NHCOPh); 4.49
(m, 4H, Ar-CH2O-); 5.01 (m, 1H, ArSCH2CH(CO2H)NHCOPh);
6.9-7.7 (m, 5H, ArNHCOPh).
The authors thank the Department of Atomic Energy for the
ORI-Award for the period 2006–2011. They also thank Ashok
Zachariah Samuel for help with the art-work.
1H NMR (d, ppm, CDCl3): 1.85 (m, 4H, ArOCH2CH2CH2-
CH2OH); 2.30 (m, 6H, Ar-CH3); 2.37 (m, 3H, Ar-CH3); 3.57 (t,
2H, ArOCH2CH2CH2CH2OH); 3.63 (t, 2H, ArOCH2CH2CH2
CH2OH); 4.03 (d, 2H, ArCH2OCH2CHCH2); 4.49 (s, 4H, Ar-
CH2O-); 5.25 (m, 2H, ArCH2OCH2CHCH2); 5.97 (m, 1H,
ArCH2OCH2CHCH2).
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