Copper oxide nanoparticles catalyzed vinylation of imidazoles with vinyl halides under ligand-free conditions

Article abstract of DOI:10.1016/j.tetlet.2010.04.022

Recyclable copper oxide nanoparticles catalyzed most efficient and straightforward protocol for the vinylation of imidazoles with vinyl halides under ligand-free conditions. Utilizing this protocol various imidazoles were cross-coupled with different substituted vinyl halides to get the corresponding products in excellent yields with the retention configuration.

Full text of DOI:10.1016/j.tetlet.2010.04.022

Tetrahedron Letters 51 (2010) 3181–3185
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Copper oxide nanoparticles catalyzed vinylation of imidazoles with vinyl
halides under ligand-free conditions
*
V. Prakash Reddy, A. Vijay Kumar, K. Rama Rao
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 December 2009
Revised 2 April 2010
Accepted 8 April 2010
Available online 11 April 2010
Recyclable copper oxide nanoparticles catalyzed most efficient and straightforward protocol for the viny-
lation of imidazoles with vinyl halides under ligand-free conditions. Utilizing this protocol various imi-
dazoles were cross-coupled with different substituted vinyl halides to get the corresponding products
in excellent yields with the retention configuration.
Ó 2010 Elsevier Ltd. All rights reserved.
N-Vinylimidazoles are important building blocks in the synthesis
of many biologically active molecules and a wide variety of industri-
ally valuable organic compounds.1 These compounds also exhibit
remarkable antifungal and antiparasitic properties.2 In addition,
N-vinylimidazoles are widely used in the synthesis of polymeric
materialswith various properties. For example, poly(N-vinylimidaz-
oles) have found growing applications in the preparation of poly-
meric dyes, catalysts, and ion-exchange resins.3
Thus, these wide ranges of applications led to various types of
processes for the synthesis of N-vinylimidazoles. Traditional
ethods involve direct addition of imidazole to alkynes,4 copper-cat-
alyzed C–N bond cross-coupling of benzimidazole with vinylboronic
acid5, and olefination of b-hydroxyimidazoles.6 The most commonly
employed strategy involves the vinylation of imidazoles with vinyl
halides.7 These procedures are rather limited in scope and selectiv-
pling of phenyl diselenide with various aryl halides by using
recyclable CuO nanoparticles under ligand-free conditions.8a In
continuation of our work on metal-catalyzed cross-coupling reac-
tions, we have explored the CuO-catalyzed synthesis of N-vinylim-
idazoles under ligand-free conditions. In general, heterogeneous
catalysts offer higher surface area and lower coordinating sites,
which are responsible for the higher catalytic activity.9 Further-
more, heterogeneous catalysis has the advantage of high atom effi-
ciency, easy product purification, and reusability of the catalyst.
However, until now, the investigation of nanoparticles as catalysts
is of limited scope.
We report, herein, the synthesis of N-vinylimidazoles by using
recyclable CuO nanoparticles as catalyst under ligand-free condi-
tions (Scheme 1). To the best of our knowledge, this is the first
recyclable coper oxide nanoparticles-catalyzed cross-coupling of
vinyl halides with imidazoles.
ity. Notable amongst them is the well-defined CuI/L-proline as a
recyclable system developed by Bao and co-workers for the synthe-
Initially, the reaction between vinyl halides (1.0 mmol) and
imidazole (1.0 mmol) was investigated to optimize the reaction
conditions. In the first instance, the amount of catalyst necessary
to promote the reaction efficiently was examined (Table 1). It is ob-
served that the variation in the amount of CuO nanoparticles had
an effective influence. While 0.5 and 1.0 mol afforded the desired
product in moderate yields (entries 1 and 2), 1.5 mol % of the cat-
alyst gave the desired product in 98% yield (entry 3). When the
amount of CuO nanoparticles was increased to 2.0 mol %, the yield
of the compound was not changed significantly and afforded the
desired product in 99% (entry 4).
sis of N-vinylimidazoles in ionic liquids at 110 °C for 20 h.7a
Over recent years great strides have been made in the field of
transition-metal-catalyzed vinylation of imidazoles with vinyl ha-
lides. The combination of transition metals and ligands has been
used to facilitate the transformation at higher temperatures.6 Most
of these metal-catalyzed reactions involve expensive and mois-
ture-sensitive catalytic systems and ligands, longer reaction times,
metal contamination of the final product, and non recyclability of
the catalyst, thus increasing the cost and limiting the scope of
the reaction. From the synthetic point of view, it is desirable to find
novel recyclable catalytic system especially under ligand-free con-
ditions for the synthesis of such highly useful organic compounds.
In the past few years, tremendous efforts have been made in the
heterogeneous catalysis for various organic transformations.8 We
have recently described an efficient method for C–Se cross-cou-
N
CuO (1.5 mmol)
KOH (1.0 equiv)
N
I
N
N
H
DMSO (2.0 mL)
5h, 80 ºC
* Corresponding author. Tel.: +91 40 27193164; fax: +91 40 27160512.
E-mail addresses: drkrrao@yahoo.com, kakulapatirama@gmail.com (K. Rama
Rao).
Scheme 1. CuO nanoparticles-catalyzed cross-coupling reaction of trans-b-iodo-
styrene with imidazole.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.022

3182
V. Prakash Reddy et al. / Tetrahedron Letters 51 (2010) 3181–3185
Table 1
Different solvents, base, as well as reaction temperature have
Amount of CuO used for synthesis of N-vinylimidazolea
been screened. Interestingly, we found that the reaction proceeded
efficiently only when DMSO was used as the solvent (Table 2, entry
11). Other solvents such as DMF were also effective but the yields
were not encouraging (Table 2, entries 6, 7, and 16), and no prod-
ucts were formed in the case of THF or water (Table 2, entries 5 and
19). The choice of KOH as the base was vital for this coupling reac-
tion (Table 2, entry, 11), as Cs2CO3 and K3PO4 though catalyze the
reaction, the yields were discouraging (Table 2, entries 3, 4, 14, and
15). The reaction when conducted at room temperature and 40 °C,
the yields observed were very low. The reaction proceeds smoothly
at 80 °C (Table 2, entry 11).
Entry
CuO (mol %)
Yield (%)
1
2
3
4
0.5
1.0
1.5
2.0
61
80
98
98
a
Reaction conditions: trans-b-iodostyrene (1.0 mmol), imidazole (1.0 mmol) CuO
(1.5 mol, KOH (1.0 equiv), DMSO (2.0 mL), 80 °C, 5 h.
Table 2
Screening of different copper catalystsa
Then the reaction was screened with several copper catalytic
systems for the synthesis of N-vinylimidazoles, and the results
are summarized in Table 2. It was observed that the combination
of nano CuO with KOH in DMSO provided the best results. How-
ever, the coupling reaction with ordinary CuO, CuI, and Cu(acac)2
gave only trace amount of the desired product. The yield was
highly dependent upon the reaction temperature, base, solvent,
and catalyst.10 The optimal reaction conditions for the vinylation
of imidazoles with vinyl halides were achieved using a combina-
tion of CuO (1.5 mol), KOH (1.0 equiv), and DMSO (2.0 mL) with
stirring for 5 h at 80 °C (Table 2, entry 12).
To expand the scope of this novel transformation, we examined
various vinyl halides with different imidazoles and benzimidazoles
for cross-coupling (Table 3).11 This protocol efficiently cross cou-
pled trans-b-iodostyrene having electron-rich, electron-neutral,
and electron-poor functionalities with various imidazoles and
benzimidazoles under the optimized reaction conditions and gen-
erated the desired products in excellent yields (Table 3). However,
the reaction of imidazoles having electron-withdrawing substitu-
ents such as 4-nitrile imidazole with trans-b-Iodostyrene did not
proceed. Even in the case of 4-nitro-imidazole, the product was ob-
tained in very low yields (Table 3, entry 15). All attempts to couple
alkyl vinyliodides with imidazoles were not successful (Table 3, en-
try 16). We further tested the coupling of trans-b-bromostyrenes
with imidazoles under the same conditions. The reaction of
N
I
N
catalyst
base, solvnt
N
N
H
Entry
Base
Solvent
Copper source
Time (h)
T (°)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
KOH
DMSO
Toluene
DMSO
DMSO
THF
CuO
CuO
CuO
CuO
CuO
CuO
24
24
24
24
24
24
24
24
24
24
5
110
110
110
110
110
110
110
110
110
110
80
40
rt
80
80
80
80
80
80
25
0
14
10
0
10
15
0
Cs2CO3
Cs2CO3
K3PO4
Cs2CO3
KOH
Cs2CO3
Cs2CO3
KOH
KOH
KOH
KOH
KOH
Cs2CO3
K3PO4
KOH
KOH
—
DMF
DMF
Cul
Cul
Cul
Toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
0
9
Cu(acac)2
Nano CuO
Nano CuO
Nano CuO
Nano CuO
Nano CuO
Nano CuO
—
98
66
20
49
31
55
0
5
5
5
5
5
DMSO
DMSO
Water
24
24
24
Nano CuO
Nano CuO
25
0
KOH
a
Reaction conditions: trans-b-iodostyrene (1.0 mmol), imidazoles (1.0 mmol)
CuO (1.5 mol), base (1.0 equiv), solvent (2.0 mL) under N2.
b
Isolated yield.
Table 3
Vinylation of imidazoles with trans-b-iodostyrenea
Entry
Iodides
Imidazoles
Product
Yieldb (%)
98
I
I
N
N
N
N
N
1
N
H
Ph
N
Ph
2
3
87
90
N
H
I
N
N
N
N
H
I
N
N
N
N
H
4
5
91
93
Cl
Cl
I
N
N
N
N
H
MeO
MeO

V. Prakash Reddy et al. / Tetrahedron Letters 51 (2010) 3181–3185
3183
Table 3 (continued)
Entry
Iodides
Imidazoles
Product
Yieldb (%)
I
N
N
N
6
7
90
89
N
H
I
Ph
N
N
Ph
N
Cl
N
H
Cl
I
I
Ph
N
N
N
Ph
N
8
9
91
88
MeO
MeO
N
H
MeO
MeO
N
N
N
H
I
I
N
N
N
N
N
H
10
11
85
88
F
F
F
F
N
N
N
H
I
I
Ph
N
N
N
Ph
N
12
13
14
84
86
—
N
H
N
N
N
H
I
I
NC
N
N
CN
N
N
N
H
O2N
N
N
NO2
15
10
—
N
H
O
N
N
O
O
I
16
N
H
O
N
a
Reaction conditions: trans-b-iodostyrene (1.0 mmol), imidazoles (1.0 mmol) CuO (1.5 mol), KOH (1.0 equiv), DMSO (2.0 mL) under N2.
Isolated yield.
b
trans-b-bromostyrenes with imidazoles proceeded smoothly to
Copper oxide nanoparticles were used directly in the next cycle.
After each cycle, the catalyst was recovered by simple centrifuga-
tion, washed with acetone, and then dried in vacuo. The recovered
nano CuO was then taken to the next cycle. The catalyst was found
to be recyclable without loss of catalytic activity up to four cycles
(Table 5).
In conclusion, we have developed a clean and efficient straight-
forward protocol for cross-coupling of imidazoles with phenyl-
substituted vinyl halides catalyzed by copper oxide nanoparticles
as recyclable catalyst under ligand-free conditions with retention
afford the desired product in reasonable yield (Table 4). However,
the coupling reaction of various imidazoles with vinyl bromides re-
quired longer reaction times to get reasonable yields of N-vinylim-
idazoles whereas shorter reaction times led to decreased yields
(Table 4, entries 1 and 2). Furthermore, the double bond geometry
of the vinyl imidazoles was retained in all the cases and the struc-
tures of all the products were determined from their analytical and
spectral (IR, 1H NMR and 13C NMR) data and by direct comparison
with authentic samples.12

3184
V. Prakash Reddy et al. / Tetrahedron Letters 51 (2010) 3181–3185
Table 4
Vinylation of imidazoles with vinyl bromides and chloridesa
Entry
Halides
Imidazoles
Product
Yieldb (%)
1
2
51c
89
Br
N
N
N
N
N
H
3
4
45c
82
Br
N
N
N
N
H
Cl
Cl
Br
Ph
N
N
Ph
5
6
79
84
N
H
Br
Ph
N
N
Ph
N
MeO
N
H
MeO
Br
N
N
N
7
8
9
80
78
20
N
H
Br
Cl
N
N
N
N
N
N
H
N
N
H
a
b
c
Reaction conditions: vinyl halides (1.0 mmol), imidazoles (1.0 mmol) CuO (2.0 mol), KOH (1.0 equiv), DMSO (2.0 mL) at 80 °C for 11 h under N2.
Isolated yield.
After 5 h.
of the double bond geometry. However, in this protocol the alkyl-
substituted vinyl halides did not yield the desired products. The
mild reaction conditions, high selectivity, operational simplicity,
and recyclability of the metal catalyst should render this method
attractive both from economic and industrial points of view as
compared to the previous methods.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.04.022.
References and notes
1. For selected examples, see: (a) Branowska, D. Synthesis 2003, 2096; (b)
Kurdaziel, K.; Glowiak, T. J. Coord. Chem. 2002, 55, 327; (c) Mano, N.; Kim, Y.;
Zhang, H. H.; Heller, A. J. Am. Chem. Soc. 2002, 124, 6480.
2. (a) Gist-Brocades, N. V. NL 8005204, 1982; (b) Ross, W. J.; Jamieson, W. B.;
McCowen, M. C. J. Med. Chem. 1973, 16, 347; (c) Hamada, Y.; Shinomoto, S.;
Yamada, I.; Koike, H. EP 162359, 1985; (d) Cockerrill, A. F.; Rackham, D. M.;
Franklin, N. C.; Norman, C. J. Chem. Soc., Perkin Trans. 2 1973, 509.
Acknowledgments
V.P.R. thanks CSIR and A.V.K. thanks UGC, New Delhi, for the
award of fellowships.
3. (a) Barker, S. J.; Storr, R. C. J. Chem. Soc., Perkin Trans.
1 1990, 485; (b)
Masquestiau, A.; Beugnies, D.; Flammang, R.; Katritzky, A. R.; Soleiman, M.;
Davis, T.; Lam, J. N. J. Chem. Soc., Perkin Trans. 2 1988, 1071; (c) Wender, P. A.;
Cooper, C. B. Tetrahedron 1986, 42, 2985; (d) Marky, M.; Schmidt, H. J.; Hansen,
H. Helv. Chim. Acta 1979, 62, 2129.
Table 5
Recycling of CuO Nanoparticlesa
N
N
4. (a) Aiscar, B. J. J.; Henkelmann, J.; Preiss, T.; Knochel, P.; Tzalis, D.; Koradin, C.
2000, EP 1055653; (b) Tzalis, D.; Koradin, C.; Knochel, P. Tetrahedron Lett. 1999,
40, 6193.
5. Lam, P. Y. S.; Vincent, G.; Clark, C. G.; Deudon, S.; Jadhav, P. K. Tetrahedron Lett.
2001, 42, 3415.
I
CuO/KOH
DMSO
N
N
H
6. (a) Cooper, G.; Irwin, W. J. J. Chem. Soc., Perkin Trans. 1 1976, 545; (b) Cooper, G.;
Irwin, W. J. J. Chem. Soc., Perkin Trans. 1 1975, 798.
Recycles
Yield (%)
Catalyst recoverya (%)
7. (a) Wang, Z. M.; Bao, W. L.; Jiang, R. Chem. Commun. 2005, 2849; (b) Shen, G.;
Lv, X.; Qiu, W.; Bao, W. Tetrahedron Lett. 2008, 49, 4556; (c) Hayat, S.; Rahman,
A.; Choudhary, M. I.; Khan, K. M.; Schumann, W.; Bayer, E. Tetrahedron 2001, 57,
9951; (d) Lebedev, A. Y.; Izmer, V. V.; Kazyulkin, D. N.; Beletskaya, I. P.;
Voskoboynikov, A. Z. Org. Lett. 2002, 4, 623; (e) Taillefer, M.; Ouali, A.; Renard,
B.; Spindler, J.-F. Chem. Eur. J. 2006, 12, 5301; (f) Tzalis, D.; Henkelmann, J.;
Heider, M. Tetrahedron Lett. 1999, 40, 6193; (g) Bao, W.; Liu, Y.; Lv, X. Synthesis
2008, 1911; (h) Mao, J.; Hua, Q.; Guo, J.; Shi, D.; Ji, S. Synlett 2008, 2011; (i) Mao,
1
2
3
4
98
96
92
92
98
95
91
91
a
Reaction conditions: trans-b-iodostyrene (1.0 mmol), imidazoles (1.0 mmol)
CuO (1.5 mol), KOH (1.0 equiv), DMSO (2.0 mL) under N2.

V. Prakash Reddy et al. / Tetrahedron Letters 51 (2010) 3181–3185
3185
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G.; Lv, X.; Qian, W.; Bao, W. Tetrahedron Lett. 2008, 49, 4556.
was recovered by simple centrifugation, washed with deionized water and
ethylacetate, and then dried in vacuo. The recovered nano CuO was used
directly in the next cycle.
8. (a) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org. Lett. 2009, 11, 951; (b)
Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org. Lett. 2009, 11, 1697; (c)
Choudary, B. M.; Kantam, M. L.; Ranganath, K. V. S.; Mahender, K.; Sreedhar, B. J.
Am. Chem. Soc. 2004, 126, 3396; (d) Choudary, B. M.; Ranganath, K. V. S.; Pal, U.;
Kantam, M. L.; Sreedhar, B. J. Am. Chem. Soc. 2005, 127, 13167.
9. (a) Pacchioni, G. Surf. Rev. Lett. 2000, 7, 277; (b) Knight, W. D.; Clemenger, K.; de
Heer, W. A.; Saunders, M.; Chou, Y.; Cohen, M. L. Phys. Rev. Lett. 1984, 52, 2141;
(c) Kaldor, A.; Cox, D.; Zakin, M. R. Adv. Chem. Phys. 1988, 70, 211.
12. Data for the representative examples of synthesized compounds: (E)-4-Phenyl-1-
styryl-1H-imidazole (Table 3, entry 2): mp 102–103 °C; IR (KBr):
m
3115, 3028,
2922, 1651 cmÀ1
;
1H NMR (200 MHz, CDCl3, TMS): d = 7.77 (d, 2H, J = 7.80 Hz),
7.72 (s, 1H), 7.50 (s, 1H), 7.38–7.22 (m, 9H), 6.73 (d, 1H, J = 14.63 Hz); 13C NMR
(50 MHz, CDCl3, TMS): d = 142.9, 136.6, 134.2, 133.2, 128.7, 128.5, 127.8, 127.1,
126.0, 124.9, 122.3, 118.4, 111.3; mass (ESI): m/z 247 [M+1]. Anal. Calcd for
(C17H14N2): C, 82.90; H, 5.73; N, 11.37. Found: C, 82.83; H, 5.65; N, 11.29.
(E)-1-(4-Methoxystyryl)-4-phenyl-1H-imidazole (Table 3, entry 8): mp 110–
10. The reaction taking place in the presence of DMSO and its absence in water
may be explained by the formation of dimsyl ion (Ref. Hunter, D. H.; Cram, D. J.
J. Am. Chem. Soc. 1966, 88, 5765.).
112 °C; IR (KBr):
m ;
3032, 2924, 1654 cmÀ1 1H NMR (200 MHz, CDCl3, TMS):
d = 7.77–7.70 (m, 3H), 7.48 (s, 1H), 7.37–7.16 (m, 6H,), 7.83 (d, 2H, J = 8.30 Hz),
6.67 (d, 1H, J = 14.35 Hz), 3.80 (s, 3H); 13C NMR (50 MHz, CDCl3, TMS):
d = 159.4, 133.4, 128.5, 127.3, 127.1, 126.7, 124.8, 120.7, 118.5, 114.2, 55.2;
mass (ESI): m/z 277 [M+1]. Anal. Calcd for (C18H16N2O): C, 78.24; H, 5.84; N,
10.14. Found: C, 78.16; H, 5.76; N, 10.06.
11. General procedure for the synthesis of vinyl imidazoles: To a stirred solution of
trans-b-iodostyrene (1.0 mmol) and imidazole (1.0 mmol) in dry DMSO
(2.0 mL) were added CuO nanoparticles (1.5 mol) followed by KOH
(1.0 equiv) at room temperature under nitrogen atmosphere. The reaction
mixture was heated at 80 °C for 5 h. The progress of the reaction was
monitored by TLC. After the reaction was complete, the reaction mixture was
allowed to cool, and a 1:1 mixture of ethyl acetate/water (20 mL) was added,
and CuO was removed by centrifuging for 1 h at 15,000 rpm. The combined
organic extracts were dried with anhydrous Na2SO4. The solvent and volatiles
were completely removed under vacuum to yield the crude product, which
was further purified by column chromatography using petroleum ether and
ethyl acetate as eluents to yield the expected product 3 (98% yield as yellow
solid). The identity and purity of the product was confirmed by 1H and 13C NMR
spectroscopic analysis.
(E)-1-(3-Fluorostyryl)-1H-benzo[d]imidazole (Table 3, entry 10): mp 130–
132 °C; IR (KBr):
m ;
3090, 2924, 1656 cmÀ1 1H NMR (300 MHz, CDCl3, TMS):
d = 8.19 (s, 1H), 7.87–7.81 (m, 1H), 7.64–7.50 (m, 2H), 7.37–7.29 (m, 3H,), 7.23–
7.12 (m, 2H), 7.04–6.98 (m, 1H), 6.92 (d, 1H, J = 14.35 Hz); 13C NMR (75 MHz,
CDCl3, TMS): d = 161.4, 143.9, 140.6, 136.9, 130.4, 130.3, 123.9, 123.2, 120.7,
118.2, 114.9, 114.6, 112.7, 112.4, 110.2; mass (ESI): m/z 239 [M+1]. Anal. Calcd
for (C15H11FN2): C, 75.62; H, 4.65; N, 11.76. Found: C, 75.56; H, 4.59; N, 11.68.
(E)-1-(4-Methylstyryl)-1H-benzo[d]imidazole (Table 3, entry 13): mp 111–
113 °C; 1H NMR (300 MHz, CDCl3, TMS): d = 8.32 (s, 1H), 7.94–7.62 (m, 1H),
7.47 (d, 1H, J = 14.35 Hz), 7.37–7.26 (m, 5H), 7.17–7.15 (m, 2H), 6.90 (d, 1H,
J = 14.35 Hz), 2.38 (s, 3H); 13C NMR (75 MHz, CDCl3, TMS): d = 143.9, 140.8,
138.0, 131.6, 129.5, 126.0, 123.7, 122.9, 120.5, 120.3, 120.1, 110.2, 21.7; mass
(ESI): m/z 235 [M+1].
Recycling of the catalyst: After the reaction was complete, the reaction mixture
was allowed to cool, and a 1:1 mixture of ethyl acetate/water (2.0 mL) was
added, and CuO was removed by centrifugation. After each cycle, the catalyst