Synthesis and polymerization of styrene monomer carrying isothiocyanate moiety and its copolymerization with HEMA based on chemo-selectivity to nucleophiles

Article abstract of DOI:10.1002/pola.26951

Isothiocyanate is a very useful functional group for post-polymerization modification by the reaction with amine or alcohol. An isothiocyanate monomer, 4-vinylbenzyl isothiocyanate, was synthesized from 4-vinylbenzyl chloride without using any harmful rea

Full text of DOI:10.1002/pola.26951

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Synthesis and Polymerization of Styrene Monomer Carrying
Isothiocyanate Moiety and Its Copolymerization with HEMA Based
on Chemo-selectivity to Nucleophiles
Ryu Yamasaki, Takeshi Endo
Molecular Engineering Institute, Kinki University, Kayanomori, Iizuka, Fukuoka 820-8555, Japan
Correspondence to: T. Endo (E-mail: tendo@moleng.fuk.kindai.ac.jp)
Received 13 June 2013; accepted 16 September 2013; published online 8 October 2013
DOI: 10.1002/pola.26951
ABSTRACT: Isothiocyanate is a very useful functional group for
post-polymerization modification by the reaction with amine or
alcohol. An isothiocyanate monomer, 4-vinylbenzyl isothiocya-
nate, was synthesized from 4-vinylbenzyl chloride without
using any harmful reagents such as thiophosgene and CS2.
The obtained monomer was successively polymerized by the
conventional radical polymerization (AIBN, 1,4-dioxane, 60 ꢀC)
to afford the corresponding polymer. The obtained polymer
was characterized by 1H NMR, FTIR, thermogravimetric analy-
sis (TGA), and differential scanning calorimetry. In contrast to
the isocyanate group, the isothiocyanate group was relatively
tolerant to alcohols, and this character enabled us to synthe-
size a copolymer of 4-vinyl benzylisothiocyanate and (2-hydrox-
yethyl methacrylate). The copolymer is transformed into
networked polymer by 1,8-diazabicyclo[5.4.0]undec-7-ene as a
promoter of the reaction between isothiocyanate and alcohol
to afford thiocarbamate. The formation of networked polymer
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was characterized by FTIR and TGA. 2013 Wiley Periodicals,
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KEYWORDS: copolymerization; isothiocyanate; modification;
polystyrene; radical polymerization
vinylbenzyl isothiocyanate monomer itself to date in
contrast to existing many examples concerning the
UV-triggered rearrangement of thiocyanate polymer to iso-
thiocyanate polymer.13–17
INTRODUCTION Isothiocyanate (2N@C@S) group have anal-
ogies with isocyanate (2N@C@O); these groups react with
amine to give corresponding thiourea and urea, respec-
tively,1,2 and this reaction has been used for a reliable way
to link two different compartments.3 However, reactivities
against alcohol are completely different between isothiocya-
nate and isocyanate. Thus, isocyanates react with alcohol to
afford carbamates, although isothiocyanates usually react
with alcohol to give thiocarbamates very slowly.4 The tardy
reaction of isothiocyantate against alcohol or water is advan-
tageous to apply to bioconjucation,5–7 which require the
chemo-selectivity toward amine over water and alcohol.
In this study, we present the utility of 4-vinylbenzyl isothiocya-
nate as the monomer for a synthesis of polymer bearing isothio-
cyanate group. In addition, we demonstrate that the
characteristic reactivity toward alcohol would be also useful for
the copolymerization with 2-hydroxyethyl methacrylate
(HEMA) which has an alcohol group. The reaction between iso-
thiocyanate and alcohol to form gel was promoted by the addi-
tion of base such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
There are some report for the polymer bearing isothiocya-
nate,8 and the synthesis and polymerization of 4-(isothiocy-
anate) styrene was reported in litaratures.9–11 This
monomer can be synthesized from 4-amino styrene by the
use of CS2 or thiophosgene which is not desirable from the
environmental standpoint.9,10 As a more easily accessible
styrene-based isothiocyanate monomer, we focused on the
4-vinylbenzyl chloride. This monomer can be prepared from
4-chloromethyl styrene in a single step,12 and the process
does not require the use of any harmful reagents such as
CS2 and thiophosgene. To the best of our knowledge, there
are no reports concerning direct polymerization of 4-
EXPERIMENTAL
Materials
4-Vinylbenzyl chloride (1) was obtained from AGC Seimi
Chemicals (Kanagawa, Japan). KSCN, NaI, DBU, tetrahydrofu-
ran (THF), and N,N-dimethylformadmie (DMF) were pur-
chased from Wako Pure Chemical Industries and used as
received. Azobisisobutyronitrile (AIBN) (Wako Pure Chemical
Industries) was recrystallized from methanol before use. 1,4-
Dioxane (Wako Pure Chemical Industries) was distilled from
LiAlH4 and used immediately.
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Measurements
1H and 13C NMR spectra were recorded on JEOL-ECS400. IR
spectra were recorded on a Thermo Scientific Nicolet iS10
spectrometer. Number average molecular weight (Mn) and
polydispersity index (Mw=Mn) were estimated by size exclu-
sion chromatography (SECꢀ) using THF as an eluent at a flow
rate of 0.6 mL=min at 40 C, performed on Tosoh chromato-
graph model HLC-8320 system equipped with Tosoh TSKgel
SuperHM-H styrogel columns (6.0 mm / 3 15 cm, 3- and
5-lm bead sizes), refractive index detector, and UV–visible
detector (254 nm). The molecular weight calibration curve
was obtained with polystyrene standards. Differential scan-
ning calorimetry (DSC) was carried out with DSC-6200
(Seiko Instrument Inc.) using an aluminum pan under 20
mL=min N2 flow at the heating rate of 5 ꢀC=min. Thermal
gravimetric analysis (TGA) was performed with TG-DTA
6200 (Seiko Instruments Inc.) using an alumiꢀna pan under a
50 mL=min N2 flow at the heating rate of 10 C=min.
Synthesis of 4-Vinylbenzyl Isothiocyanate (2)
This compound was synthesized according to the reported
method.12 4-Vinylbenzyl chloride (1) (7.60 g, 50 mmol) was
dissolved with DMF (30 mL), and KSCN (5.82 g, 60 mmol),
and NaI (2.80 g, 18.7 mmol) was added. The mixture was
heated to 150 ꢀC and stirred for 30 min. After cooled to
room temperature, the solution was diluted with Et2O (150
mL), and washed with saturated NH4Cl aq. (100 mL). The
water layer was extracted with Et2O (150 mL 3 3), the com-
bined organic layer was washed with saturated NH4Cl aq.
(100 mL), and dried over anhydrous Na2SO4. After filtration,
the solution was evaporated and purified by silica gel col-
umn chromatography (eluent; AcOEt:n-hex 5 1:30) to afford
pale yellow oil (4.90 g, 56%). 1H NMR (400 MHz, CDCl3, d):
7.42 (d, 2H, J 5 8.1 Hz; ArH), 7.27 (d, J 5 8.1 Hz, 2H; ArH),
6.71 (dd, J 5 17.6, 10.9 Hz, 1H; PhACH@CH3), 5.77 (d, J 5
17.4 Hz, 1H; PhACH@CH2), 5.29 (d, J 5 11.0 Hz, 1H;
PhACH@CH2), 4.69 (s, 2H; PhACH2AN); 13C NMR (100 MHz,
CDCl3, d): 137.7 (C1), 136.0 (ArACH@CH2), 133.6 (ArC),
129.2 (NCS), 127.0 (ArC), 126.7 (ArC), 114.7 (PhACH@CH2),
48.4 (PhACH2ANCS); IR (neat): m 5 2173 (s, ANCS), 2092
(vs, ANCS), 1511 (w), 1437 (w), 1342 (w), 990 (w), 913
(w), 824 (w), 721 (w), 690 cm21 (w); HRMS (m=z): calcd
for C10H9OS, 175.0456; found, 175.0453 [M 1 H]1.
SCHEME 1 Synthesis of 4-vinyl benzylisothiocyanate (2).
Model Reaction of Benzyl Isothiocyanate and 1-Propanol
Benzylisothiocyanate 5 (200 mg, 1.34 mmol) was dissolved
in THF (6.7 mL) and 1-propanol (100 mL, 1. 34 mmol) (and
DBU for the catalytic reaction) was added. Stirred for 6 h at
ꢀ
25 C, the mixture was evaporated and purified by silica gel
column chromatography. The compound characterization
data of thiocarbamate 6 was identical to the one previously
reported.18
Polymerization of 4-Vinylbenzyl Isothiocyanate (4)
To 1 (500 mg, 2.85 mmol) placed in a glass ampule tube with
stirring bar was added AIBN (9.36 mg, 57 lmol) in freshly
distilled 1,4-dioxane (1.4 mL). The tube was cooled, evac-
uated, sealed off, and heated at 60 ꢀC for the designated
period with stirring. Then the mixture was cooled to room
temperature, and added to methanol (100 mL) dropwise. The
resulting precipitate was collected by centrifugation (3000
rpm 3 30 min), washed with methanol, and dried in reduced
Copolymerization of 4-Vinylbenzyl Isothiocyanate (2)
and HEMA
Copolymer of 2 and HEMA was prepared based on the method
for homopolymer 4. 1H NMR (400 MHz, CDCl3, d): 6.2–7.2
(ArH), 4.64 (br, PhACH2AN), 4.67 (2H, PhACH2AN), 0.4–2.0
(ACH2A (main chain) and ACH2(CH3) ACH2A); IR (KBr): m 5
3483 (w), 2925 (w), 2172 (s, ANCS), 2083 (s, ANCS), 1720 (m,
C@O), 1512 (w), 1439 (w), 1422 (w), 1338 (w), 1185 (m), 1076
(w), 815 (w), 682 cm21 (w).
1
pressure to afford colorless solid as polymer 4. H NMR (400
MHz, CDCl3, d): 6.97 (2H, ArH), 6.49 (2H, ArH), 4.67 (2H,
PhACH2AN), 3.4–4.0 (COOCH2A and ACH2CH2OH); IR (KBr):
m 5 2924 (w), 2171 (m, ANCS), 2087 (vs, ANCS), 1511 (w),
1421 (w), 1338 (w), 815 (w), 682 cm21 (w).
Formation of Networked Polymer (8)
Copolymer 7 (30 mg, Table 3, Entry 1) was placed in a vial,
and dissolved with THF (1 mL) and DBU (45 mL, 0.3 mmol)
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RESULTS AND DISCUSSION
TABLE 1 Results of Radical Polymerization of 2
Synthesis of 4-Vinyl Benzylisothiocyanate
The synthesis of 4-vinyl benzylisothiocyanate has been
reported in the patent.12 The reaction of 4-chloromethyl sty-
rene (1) with NH4SCN at room temperature gives thiocya-
nate (3);16 however, the reaction with KSCN at high
temperature (150 ꢀC) afforded isothiocyanate (2) as a main
product (Scheme 1). The IR spectrum of compound 2
showed a characteristic peak of isothiocyanate around 2100
cm21 19 and totally different from that of 3.16 This com-
,
pound was stable and can be stored in refrigerator without
any sign of decomposition at least for a week. It is notewor-
thy that this isothiocyanate monomer (2) is easy to prepare
and handle and the use of harmful reagents such as thio-
phosgene and CS2 was not necessary. The isomerization of
thiocyanate to isothiocyanate is controlled under thermody-
namic equilibrium; the reaction of 2 or 3 in the presence of
Reaction
TIME (h)
1
Conversiona
Yield
(%)
13
b
b
Entry
(%)
19
Mn
Mw=Mn
1.91
1
2
3
4
5
12,000
12,200
14,400
13,600
15,300
3
24
39
62
82
17
41
61
77
1.95
6
2.02
12
24
2.25
ꢀ
catalytic amount of NaI at 150 C gave almost a similar ratio
2.73
(2=3) of the product.20
Estimated from 1H NMR.
a
b
Estimated by GPC (eluent 5 THF, polystyrene standards).
Homopolymerization of 4-Vinyl Benzylisothiocyanate
To the best of our knowledge, the homopolymerization of 2
has not been reported to date, although an isomerization of
thiocyanate polymer into isothiocyanate by UV-irradiation
has been widely used.13–17 The polymerization reaction of 2
was performed in the presence of AIBN (2 mol %) in 1,4-
dioxane at 60 ꢀC. The reaction was quenched by adding the
solution into methanol dropwise, which is not possible for
the case of polymer containing isocyanate group, and the
insoluble part was collected after centrifuge as the polymer 4.
was added via syringe. Stirred for 6 h at room temperature,
the formed pale yellow gel was collected by suction and
thoroughly washed with THF and dried in vacuum to afford
as pale yellow powder (33 mg). IR (KBr): m 5 2927, 2166 (s,
ANCS), 2054 (s, ANCS), 1723 (m, C@O), 1644 (s, thiocarba-
mate), 1511, 1385, 1443, 1322, 1200, 1106, 1019, 976, 842,
813.
FIGURE 1 1H NMR (400 MHz) of polymer 4 in CDCl3.
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FIGURE 2 FTIR spectra of polymer 4.
FIGURE 4 DSC analysis of polymer 4.
To find the ideal condition for the polymerization, we con-
ducted the reaction with various reaction time (1 h, 3 h, 6 h,
12 h, and 24 h), and the data of each polymers were col-
lected as shown in Table 1. The longer the reaction time
was, the better the conversion of 1 and yield of polymer
was. As typical for the chain polymerization, the number
averaged molecular weight of polymer (Mn) was almost
unchanged among those polymers, however, the Mw=Mn was
increased by extending reaction time. This implies that some
intramolecular reactions might proceed by the period of the
reaction.
at 84 ꢀC, being comparable to the other styrene-based
polymers.
Model Reaction of Benzyl Isothiocyanate and Alcohol
To make sure the reactivity of benzyl isothiocyanate toward
alcohol, model reaction was performed. The reactions of ben-
zyl isothiocyanate and alcohol (methanol, ethanol, 1-propa-
nol) were reported in a harsh condition;18 however we
investigated the reactivity under mild condition using benzyl
isothiocyanate and 1-propanol (Table 2). To investigate the
stability of isothiocyanate in alcohol, benzyl isothiocyanate
was reacted with 1 equiv of 1-propanol in THF at 25 ꢀC for
6 h. No reaction was observed by 1H NMR and the benzyl
isothiocyanate was recovered in 97%. To promote the reac-
tion, we added DBU as a catalyst.21 Although the effect of
DBU was impressive, the reaction was proceeded to afford
thiocarbamate (6) in 53% isolated yield when 0.5 equiv of
DBU was used. Even with the case that 1 equiv of DBU was
used, the yield of 6 was marginally improved to 69%.
The polymer 4, which was reacted for 6 h, was soluble (2
mg=mL) in the most of organic solvent such as DMF, DMSO,
CHCl3, THF, AcOEt, toluene, and acetone, but insoluble in n-
hexane and methanol. The structure of the polymer was
characterized by 1H NMR and IR spectrum (Figs. 1 and 2).
These spectra showed that the isothiocyanate group of the
polymer was kept intact even after the free radical polymer-
ization and the treatment with methanol.
Synthesis of Copolymers of 2 and HEMA
The characteristic reactivity of isothiocyanate monomer was
applied to synthesize copolymers with HEMA. Three
The thermal properties of polymer 4 reacted for 6 h (Table
1, Entry 3) was also investigated by TGA and DSC analysis.
The results of TG and DSC analyses of polymer 4, reacted for
6 h (Table 1, Entry 3), are shown in Figures 3 and 4, respec-
tively. The polymer exhibited Td5 (5 wt % decomposition
TABLE 2 Model Reaction of Benzyl Isothiocyanate 5 and 1-
Propanol
ꢀ
temperature) at 314 C and Tg (glass transition temperature)
Entry
DBU (equiv)
Recovery of 5 (%)
Yield of 6 (%)
1
2
3
0
97
24
19
0
0.5
1
53
69
FIGURE 3 Thermogravimetric analysis of polymer 4.
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TABLE 3 Results of Copolymerization of 2 and HEMA
b
b
Entry
Feed Ratio 2
HEMA (mol %)
Compositiona
2
HEMA (mol %)
Yield (%)
Mn
Mw=Mn
1
2
3
75
50
25
25
50
75
68
45
27
32
55
73
28
28
14
21,100
30,800
49,900
1.97
2.83
3.89
a
b
Estimated from 1H NMR.
Estimated by GPC (eluent 5 THF, polystyrene standards).
copolymers, with a different ratio of 2 and HEMA as shown
in Table 3, were synthesized by radical polymerization (Table
3). Polymers were obtained successively as a precipitate in
MeOH. All obtained copolymer of 2 and HEMA has larger Mn
than that of homopolymer of 2 by introducing HEMA unit,
though Mw=Mn of copolymers also increased along with the
increase of the content of HEMA; this could be partially
attributed to progress of the reaction between alcohol and
isothiocyanate. In addition, the reaction might have to do
with the phenomenon that copolymers which contained
HEMA part over 50 mol % (entry 2 and 3) became gel by
standing at room temperature for several hours. Because the
polymer with high HEMA content have a high local concen-
tration of alcohol moiety enough to react with isothiocyanate
even in the absence of DBU.18
temperature and this reactivity is advantageous for applica-
tion as a latent hardener. To investigate the detail of the
structure of the obtained networked polymer (8), we per-
formed FTIR analysis (Fig. 5) and TG analysis (Fig. 6).
The FTIR analysis of the above obtained networked poly-
mer showed an appearance of peak around 1600 cm21
which is typical of thiocarbamate. The isothiocyanate peak
was remained in the IR spectrum of the networked polymer
since there were remaining isothiocyanates even if the all
alcohol had reacted with isothiocyanate (Fig. 5). The TG
analysis of the polymer before and after the reaction exhib-
ited an observable change. The copolymer before the reac-
tion (7, Table 2, Entry 1) began its weight loss around 280
ꢀ
ꢀC, and a steep weight loss was observed around 400 C, as
observed in homopolymer (4) (Fig. 3). In contrast, the net-
worked polymer (8) began its gradual weight loss as early
The copolymer (7) composed of 68% of 2 (Table 3, Entry 1)
can be transformed to the networked polymer (8) by the
reaction of isothiocyanate and alcohol groups mediated by
DBU (Scheme 2). It took 6 h to be observed as gel at room
ꢀ
as around 100 C to the point that a steep weight loss, sim-
ilar to that of 4 and 5, around 400 ꢀC (Fig. 6). The heat-
lability of networked polymer could be attributed to the
thiocarbamate group formed by the reaction of isothiocya-
nate and alcohol.
SCHEME 2 Formation of networked polymer 8 by the addition
FIGURE 5 FTIR spectrum of copolymer (7) and networked poly-
mer (8).
of DBU.
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CONCLUSIONS
In this study, we described the synthesis and polymerization
of 4-vinyl benzylisothiocyanate. This isothiocyanate monomer
is easily synthesized by single step from commercially avail-
able 4-vinyl benzylchloride and tolerable in the presence of
alcohol without any protection. In addition, this homopoly-
merization by conventional free-radical condition was suc-
cessful, and the benzyl isothiocyanate group remained stable
during conventional radical polymerization condition. The
characteristic reactivity of isothiocyanate group was applica-
ble for the copolymerization with HEMA, which is not possi-
ble for isocyanate monomer due to its harsh reactivity with
alcohol. This copolymer formed networked polymer after
addition of DBU.
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