Poly(N-vinylimidazole) as efficient and recyclable catalyst for the addition of thiols to michael acceptors in aqueous medium

Full text of DOI:10.1134/S1070428007110279

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 11, pp. 1733–1736. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © I.P. Beletskaya, E.A. Tarasenko, A.R. Khokhlov, V.S. Tyurin, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43,
No. 11, pp. 1732–1735.
SHORT
COMMUNICATIONS
Dedicated to Professor Miguel Yus
on the 60th anniversary of his birth
Poly(N-vinylimidazole) as Efficient and Recyclable Catalyst
for the Addition of Thiols to Michael Acceptors
in Aqueous Medium
I. P. Beletskayaa, E. A. Tarasenkoa, A. R. Khokhlovb, and V. S. Tyurina
a Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences,
Leninskii pr. 31, Moscow, 119991 Russia
e-mail: beletska@org.chem.msu.ru
b Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
Received August 30, 2007
DOI: 10.1134/S1070428007110279
Imidazole ring is a structural fragment of the amino
acid histidine which is included in almost all enzymes.
It is known that imidazole is capable of catalyzing
a number of biochemical processes [1, 2]. We previ-
ously showed that poly(N-vinylimidazole) can be used
as polymeric support (ligand) for palladium and that
such system is an efficient and recyclable catalyst for
cross-coupling reactions [3]. Moreover, poly(N-vinyl-
imidazole) successfully simulates natural enzymes
based on peptide macromolecules [4].
simple and efficient procedures for the preparation of
such compounds was especially intense in the past
decade and is now in progress [6–17]. Here, specific
attention is given to the use of nontoxic solvents and
catalysts [10–17].
In the present study we made an attempt to catalyze
addition of thiols to Michael acceptors in aqueous or
aqueous–alcoholic medium at room temperature by
poly(N-vinylimidazole) with a molecular weight of
75300 as recyclable organic catalyst. It is known that
benzenethiol adds at the double C=C bond in electron-
deficient olefins in the absence of a catalyst [12].
Taking into account the ability of imidazole to
catalyze certain reactions, we though it to be expedient
to test it for catalytic activity in analogous processes.
Potential advantages of poly(N-vinylimidazole) as cat-
alyst are its solubility in water and aqueous media and
the possibility for repeated use.
Table 1. Reaction of benzenethiol with methyl acrylatea
Run no.
Solvent
No solvent
Reaction time, h Yield, b %
1
2
24
50
Conjugate addition of thiols to α,β-unsaturated car-
bonyl compounds underlies a widely used method for
the synthesis of β-sulfanyl-substituted carbonyl deriva-
tives which exhibit biological activity [5]. Search for
EtOH
04
24
19
58
3
4
5
6
H2O
04
04
04
04
095 (10)
98
EtOH–H2O, 1:1c
EtOH–H2O, 3:2d
i-PrOH–H2O, 1:1d
Scheme 1.
100 (33)
72
SH
+
COOMe
S
H2C
a
Molar ratio thiol–alkene–PVI (monomer unit) 1.0:1.2:0.1.
According to the H NMR data using dimethyl terephthalate as
b
1
reference. In parentheses is given the yield in the absence of
PVI (10 mol %), 20–25°C
COOMe
catalyst.
c
Heterogeneous mixture.
Homogeneous mixture.
d
I
1733

BELETSKAYA et al.
1734
Scheme 2.
PVI (10 mol %), EtOH–H2O (3:2)
20–25°C
Z
X
Y
Z
X
Y
RSH
+
RS
I–XII
I–VI, R = Ph; VII–XII, R = n-C6H13; I, VII, X = COOMe, Y = Z = H; II, VIII, X = CN, Y = Z = H; III, IX, X = Z = COOMe, Y = H;
IV, X, X = COOEt, Y = Me, Z = H; V, XI, X = COOMe, Y = CH2COOMe, Z = H; VI, XII, XZ = C(O)CH2CH2CH2, Y = H.
However, reactions of alkanethiols with unsaturated
compounds used in the present work required the pres-
ence of a base.
fanyl)propionate (I) were 100, 99, 100, 100, and
100%, respectively (according to the 1H NMR data).
Likewise, Michael addition of benzenethiol to other
electron-deficient olefins smoothly occurred under the
above conditions (Scheme 2, Table 2). Exceptions
were only olefins having a substituent in the α-position
with respect to the electron-withdrawing group. Pre-
sumably, the reason is reduced electrophilicity of the
double bond due to the presence of a donor group
rather than steric factor (cf. run nos. 4, 5 and 10, 11;
Table 2). Not only benzenethiol but also hexane-1-thiol
reacted with the olefins used. However, the most
important is that the catalyst can be readily separated
from the product and used repeatedly.
Thus we showed that poly(N-vinylimidazole) is
an accessible, effective, and recyclable organic catalyst
for the addition of aromatic and aliphatic thiols to
Michael acceptors; it ensures the reaction to be per-
formed in nontoxic aqueous or aqueous–alcoholic
medium under mild conditions. Studies aimed at ex-
Using the reaction of benzenethiol with methyl
acrylate as model (Scheme 1) we found optimal condi-
tions for the process: solvent ethanol–water (3:2), re-
action time 4 h (Table 1), amount of poly(N-vinyl-
imidazole) (PVI) 10 mol %. Obviously, the presence of
water is important. It favors dissociation of benzene-
thiol, while PVI (being a base) acts as proton carrier.
The reaction occurs under mild conditions (room tem-
perature), and the yield of methyl 3-(phenylsulfanyl)-
propionate is quantitative. Using the same model reac-
tion (Table 1, run no. 5) we examined the possibility
for recycling of the catalyst. In each subsequent cycle,
after removal of compound I from the reaction mixture
by extraction, required amounts of water, ethanol, and
reactants were added to the remaining aqueous phase.
We observed no loss in catalytic activity in five con-
secutive cycles: the yields of methyl 3-(phenylsul-
Table 2. Addition of thiols to activated alkenes in ethanol–water (3:2) at 20–25°Ca
Run no.
Thiol
PhSH
Alkene
CH2=CHCOOMe
Reaction time, h
Product
Yield,b %
01
02
03
04
05
06
07
08
09
10
11
12
04
99
95
I
PhSH
CH2=CHCN
05
II
PhSH
MeOC(O)CH=CHCOOMe-trans
CH2=C(Me)COOEt
03
92
c20c
III
IV
V
PhSH
6 (50°C) + 6 (80°C)
PhSH
MeOC(O)C(=CH2)CH2COOMe
Cyclohex-2-en-1-one
CH2=CHCOOMe
48
03
02
02
02
48
48
03
82
PhSH
99
VI
VII
VIII
IX
X
n-C6H13SH
n-C6H13SH
n-C6H13SH
n-C6H13SH
n-C6H13SH
n-C6H13SH
95
CH2=CHCN
c87c
c97c
c11c
c93c
93
MeOC(O)CH=CHCOOMe-trans
CH2=C(Me)COOEt
MeOC(O)C(=CH2)CH2COOMe
Cyclohex-2-en-1-one
XI
XII
a
b
c
Molar ratio thiol–alkene–PVI (monomer unit) 1.0:1.2:0.1.
Yield of the isolated product.
According to the 1H NMR data using dimethyl terephthalate as reference.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 11 2007

POLY(N-VINYLIMIDAZOLE) AS EFFICIENT AND RECYCLABLE CATALYST
1735
tending the scope of application of this catalyst with
respect to other substrates are now in progress.
δC, ppm: 13.88 (C6′), 22.39 (C5′), 28.34 (C3′), 29.03
(C2′), 31.23 (C1′ or C4′), 31.43 (C1′ or C4′), 36.26, 41.31,
51.88 (CH3O), 52.19 (CH3O), 171.08 (CO), 172.18
(CO). Mass spectrum: m/z 262 (100%) [M]+.
Poly(N-vinylimidazole), M 75300, was synthesized
according to the procedure described in [3].
Ethyl 3-(hexylsulfanyl)-2-methylpropionate (X).
1H NMR spectrum, δ, ppm: 0.89 t (3H, CH3, J =
6.8 Hz), 1.23–1.43 m [12H, CH3, CH3(CH2)3], 1.55–
1.60 m [2H, CH3(CH2)3CH2], 2.52 t (2H, CH2S, J =
7.4 Hz), 2.56 d.d (1H, CH2CH, J = 6.9, 12.8 Hz),
2.62–2.71 m (1H, CHMe), 2.84 d.d (1H, CH2CH, J =
6.9, 12.8 Hz), 4.16 q (2H, CH2O, J = 7.1 Hz). Mass
spectrum: m/z 232 (100%) [M]+.
Addition of thiols to electron-deficient alkenes in
the presence of poly(N-vinylimidazole (general pro-
cedure). Poly(N-vinylimidazole), 9.4 mg (0.1 mmol,
calculated per monomer unit), was dissolved in 5 ml of
a 3:2 ethanol–water mixture, 1.2 mmol of the corre-
sponding alkene and 1 mmol of thiol were added, and
the mixture was stirred at room temperature until the
reaction was complete (Table 2). The mixture was then
extracted with methylene chloride, the extract was
dried over sodium sulfate, the solvent was distilled off
under reduced pressure, and the product was isolated
by column chromatography using methylene chloride–
petroleum ether as eluent. Compounds I–XII were
colorless liquids. Their structure was confirmed by the
Dimethyl 2-(hexylsulfanylmethyl)succinate (XI).
1H NMR spectrum, δ, ppm: 0.85 t (3H, CH3, J =
6.8 Hz), 1.20–1.29 m [4H, CH3(CH2)2], 1.29–1.38 m
[2H, CH3(CH2)2CH2], 1.48–1.58 m (2H, J = 7.3 Hz),
2.47 t (2H, J = 7.3 Hz), 2.63 d.d (1H, J = 8.1, 13.4 Hz),
2.68 d.d (1H, J = 5.6, 17.1 Hz), 2.75 d.d (1H, J = 8.1,
16.9 Hz), 2.85 d.d (1H, J = 5.9, 13.5 Hz), 3.03 m (1H),
3.65 s (3H, CH3O), 3.69 s (3H, CH3O). 13C NMR spec-
trum, δC, ppm: 13.88 (C6′), 22.41 (C5′), 28.34 (C3′),
29.28 (C2′), 31.26 (C1′ or C4′), 32.36 (C1′ or C4′), 33.36
(CH2), 34.59 (CH2S), 41.34 (CH), 51.71 (CH3O),
51.99 (CH3O), 172.04 (CO), 173.67 (CO). Mass spec-
trum: m/z 276 (100%) [M]+.
13
1H and C NMR and MALDI-TOF mass spectra. The
spectral data for the newly synthesized compounds are
given below.
Dimethyl 2-(phenylsulfanylmethyl)succinate (V).
1H NMR spectrum, δ, ppm: 2.74 d.d (1H, CH2CO, J =
5.3, 16.8 Hz), 2.82 d.d (1H, CH2CO, J = 7.3, 16.8 Hz),
3.04–3.12 m (2H, CH2S), 3.34 m (1H, CHCO), 3.66 s
(6H, CH3O), 7.23 t (1H, p-H, J = 7.3 Hz), 7.30 t (2H,
m-H, J = 7.6 Hz), 7.39 d (2H, o-H, J = 7.1 Hz).
13C NMR spectrum, δC, ppm: 34.44 (CH2), 35.40
(CH2S), 41.13 (CH), 51.81 (CH3O), 52.11 (CH3O),
126.73 (Cp), 129.05 (Carom), 130.19 (arom), 134.97 (Ci),
171.88 (CO), 173.33 (CO). Mass spectrum: m/z 268
(100%) [M]+.
1
3-(Hexylsulfanyl)cyclohexanone (XII). H NMR
spectrum, δ, ppm: 0.88 t (3H, J = 6.7 Hz), 1.24–1.32 m
(4H), 1.32–1.41 m (2H), 1.52–1.60 m (2H, J = 7.5 Hz),
1.66–1.76 m (2H), 2.09–2.18 m (2H), 2.29–2.41 m
(3H), 2.54 t (2H, J = 7.5 Hz), 2.70 d.d (1H, J = 4.3,
14.2 Hz), 3.01–3.09 m (1H). 13C NMR spectrum, δC,
ppm: 13.97 (C6′), 22.48 (C5′), 24.25, 28.58, 29.64,
30.53, 31.37, 31.65 (CH2), 40.93 (C3), 42.74 (C6),
48.24 (C2), 208.97 (CO). Mass spectrum: m/z 214
(100%) [M]+.
1
3-(Hexylsulfanyl)propionitrile (VIII). H NMR
spectrum, δ, ppm: 0.88 t (3H, CH3, J = 6.8 Hz), 1.23–
1.32 m [4H, CH3(CH2)2], 1.33–1.42 m [2H,
CH3(CH2)2CH2, J = 7.0 Hz], 1.53–1.62 m [2H,
CH3(CH2)3CH2, J = 7.4 Hz], 2.58 t (2H, CH2S, J =
7.4 Hz), 2.62 t (2H, SCH2CH2CN, J 7.3 Hz), 2.77 t
(2H, SCH2CH2CN, J = 7.3 Hz). 13C NMR spectrum,
δC, ppm: 13.89 (C6′), 18.83 (C2), 22.42 (C5′), 27.56
(C3), 28.34 (C3′), 29.33 (C2′), 31.27 (C1′ or C4′), 32.24
(C1′ or C4′), 118.30 (CN). Mass spectrum: m/z 171
(100%) [M]+.
All reactions were carried out under argon. Their
progress was monitored by TLC on 60 F254 silica gel
plates (Merck). Silica gel Merck 60 (0.040–0.063 mm)
1
13
was used for column chromatography. The H and C
NMR spectra were recorded on a Bruker AMX-400
spectrometer at 400.13 and 100.61 MHz, respectively,
using CDCl3 as solvent. MALDI-TOF mass spectra
were obtained on a Bruker Daltonics Ultraflex
instrument.
Dimethyl 2-(hexylsulfanyl)succinate (IX).
1H NMR spectrum, δ, ppm: 0.86 t (3H, CH3, J =
7.0 Hz), 1.21–1.29 m [4H, CH3(CH2)2], 1.30–1.37 m
[2H, CH3(CH2)2CH2], 1.49–1.61 m [2H, CH3(CH2)3-
CH2, J = 7.1 Hz], 2.56–2.69 m (3H), 2.98 d.d (1H, J =
9.8, 16.9 Hz), 3.64 d.d (1H, J = 5.6, 9.8 Hz), 3.66 s
The authors thank Russian Academy of Sciences
(Chemistry and Materials Science Division, program
for fundamental research no. 4, “Design and Study on
Macromolecules and Macromolecular Structures of
New Generations”), and American Foundation for
Civilian Research conjunctly with the Federal Science
13
(3H, CH3O), 3.73 s (3H, CH3O). C NMR spectrum,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 11 2007

BELETSKAYA et al.
1736
6. Fetterly, B.M., Jana, N.K., and Verkade, J.G., Tetra-
hedron, 2006, vol. 62, p. 440.
and Innovation Agency of the Russian Federation
(joint project no. RUC1-2802-MO-06) for financial
support of this work.
7. Chu, C.-M., Gao, C., Sastry, M.N.V., and Yao, C.-F.,
Tetrahedron Lett., 2005, vol. 46, p. 4971.
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