C-arylation reactions catalyzed by CuO-nanoparticles under ligand free conditions

Article abstract of DOI:10.3762/bjoc.6.35

CuO-nanoparticles were found to be an excellent heterogeneous catalyst for C-arylation of active methylene compounds using various aryl halides. The products were obtained in good to excellent yield. The catalyst can be recovered and reused for four cycles with almost no loss in activity.

Full text of DOI:10.3762/bjoc.6.35

C-Arylation reactions catalyzed by
CuO-nanoparticles under ligand free conditions
Mazaahir Kidwai*, Saurav Bhardwaj and Roona Poddar
Full Research Paper
Open Access
Address:
Beilstein Journal of Organic Chemistry 2010, 6, No. 35.
Green Research Laboratory, Department ofChemistry, University of
Delhi, Delhi, India 110007
doi:10.3762/bjoc.6.35
Received: 04 February 2010
Accepted: 25 March 2010
Published: 15 April 2010
Email:
Mazaahir Kidwai* - kidwai.chemistry@gmail.com
*
Corresponding author
Associate Editor: I. Marek
Keywords:
© 2010 Kidwai et al; licensee Beilstein-Institut.
License and terms: see end of document.
active methylene compounds; C-arylation; heterogeneous catalyst;
recyclability
Abstract
CuO-nanoparticles were found to be an excellent heterogeneous catalyst for C-arylation of active methylene compounds using
various aryl halides. The products were obtained in good to excellent yield. The catalyst can be recovered and reused for four cycles
with almost no loss in activity.
Introduction
Carbon-carbon (C–C) bond formation is one of the most ition to these problems, the major drawback is that the majority
important reactions in organic synthesis [1-3]. The resulting of catalysts cannot be reused [19]. To overcome from these
compounds formed from C–C coupling are valuable synthons in problems, we have investigated a new catalytic system for
organic synthesis [4-7]. However, C-arylation reactions have C-arylation.
not been investigated to the same extent as other C–C bond
forming reactions.
Nanocrystalline metal oxides find numerous applications, e.g.,
as active adsorbents for gases [20], the destruction of hazardous
A great deal of attention has been focused on the development materials [21] and the oxidation of volatile organic compounds
of Pd catalyzed arylation [8-11]. Another important protocol [22]. In addition, metal oxide nanoparticles have been used as
involves arylation of activated methylene compounds mediated heterogeneous catalysts for various organic transformations [23-
by copper salts [12,13]. Recently, proline has also been used 28]. The high reactivity of CuO-nanoparticles (CuO-np) is due
along with CuI for C-arylation [14]. But some of the methods to the high surface area of nanoparticles combined with unusual
suffer from serious drawbacks and limitations, for example, reactive morphologies. Moreover, heterogeneous catalysts are
long reaction times [15,16], the high cost of Pd catalysts [17,18] easy to separate and can be recycled. This is very beneficial for
and the need for stoichiometric amounts of copper salts. In add- industrial process in the green chemistry domain.
Page 1 of 6
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 35.
In continuation with our research program to explore different
methodologies for the synthesis of organic compounds [29,30]
and the role of transition metal nanoparticles as catalysts in
organic reactions [31-33], we now report the synthesis of
Table 1: C-arylation reaction catalyzed by different Cu catalystsa.
Entry
Catalyst
Time (h)
Yieldb (%)
3
-arylpentane-2,4-diones and diethyl 2-aryl-malonates using
1
2
3
4
Cu(OAc)2
Cu-np
10
10
10
8
20
10
24
80
CuO-nanoparticles as a heterogeneous catalyst.
CuO
CuO-np
Results and Discussion
aReaction conditions: acetylacetone (3 mmol), iodobenzene (1 mmol),
0 mol % of catalyst, Cs2CO3 (0.5 mmol), DMSO; temperature 80 °C;
N2; 1 atm.
The reaction was carried out several times in order to establish
the optimum ratio of reactants. Iodobenzene and acetylacetone
were employed as model substrates in a 1:3 ratio. When the
iodobenzene (1 mmol) and acetylacetone (3 mmol) were stirred
with Cs2CO3 (0.5 mmol) at 80 °C in DMSO, in the presence of
1
bIsolated and optimized yield.
CuO-nanoparticles (10 mol %), 3-phenyllpentane-2,4-dione was In addition, catalytic activity of CuO-nanoparticles was evident
obtained in 80% yield (Scheme 1).
since no product was formed in its absence. The increased cata-
lytic activity of CuO-nanoparticles over the commercially avail-
able bulk CuO may be attributed to the higher surface area of
CuO-nanoparticles. This is thought to be due to morphological
differences which have been shown in the TEM image. The
number of reactive sites on the surface is small in the case of
larger crystallites and considerably greater in the case of smaller
crystallites (Figure 1).
Scheme 1: Synthesis of 3-phenylpentane-2,4-dione using CuO-nano-
particles.
To investigate further the surface morphology of CuO-nano-
particles, powder XRD and TEM images were taken. Figure 1
Other copper salts such as Cu(OAc)2 and ordinary CuO were shows the XRD pattern of CuO-nanoparticles in which diffrac-
found to be inferior to CuO-nanoparticles and gave low yields tion peaks can be indexed to a monoclinic structure. The intense
of 3-phenylpentane-2,4-dione. Moreover, Cu-nanoparticles diffraction peak at an angle 38.4 shows index plane (111) which
which have been used for O-arylation and S-arylation [34,35], contains more basic sites with higher density as compared to
were not effective in the coupling reaction (Table 1).
bulk CuO.
Figure 1: Powder X-ray diffraction pattern and TEM image of nano CuO (fresh).
Page 2 of 6
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 35.
During optimization of reaction conditions, the model reaction
was carried out in different solvents. It was found that DMSO
was the most effective solvent compared to the other solvents
used as shown in Table 2. This is not surprising in view of the
fact that the reaction intermediate is a carbanion and therefore
will have a greater stability in a polar solvent.
Table 2: CuO-nanoparticles catalyzed coupling reaction of acet-
ylacetone and iodobenzene in various solventsa.
Scheme 2: Synthesis of 3-phenylpentane-2,4-dione using CuO-nano-
particles.
Entry
Solvent
Time (h)
Yieldb (%)
tron donating groups. All these results are summarized in
Table 3.
1
2
3
4
DMSO
Toluene
THF
8
80
8
15
15
15
12
32
Acetonitrile
The above results encouraged us to investigate further reactions.
Under similar reaction conditions, diethyl malonate was treated
with iodobenzene to give the desired product in 78% yield
(Scheme 3). The reaction was then repeated with a variety of
aryl halides. The results are summarized in Table 4.
aReaction conditions: acetylacetone (3 mmol), iodobenzene (1 mmol),
0 mol % CuO-nanoparticles, Cs2CO3 (0.5 mmol), solvent; temperature
0 °C; N2; 1 atm.
1
8
bIsolated and optimized yield.
Moreover, the advantage of the nanoparticles is that, unlike
other catalysts, their use is not restricted by their solubility, as
the nanoparticles can be dispersed in the desired solvent by agit-
ation or slight sonication.
When an equimolar mixture of chlorobenzene and iodobenzene
was treated with acetylacetone under similar reaction condi-
tions, the chlorobenzene was largely unreactive. This shows that
the reaction is highly selective towards the halogen present in
the aryl halide (Scheme 2).
Scheme 3: Synthesis of diethyl 2-aryl-malonate using CuO-nano-
particles.
The observed decrease in reactivity in the order p-nitroiodoben-
To study the scope of this procedure, acetylacetone was reacted zene > iodobenzene > p-methyliodobenzene > 1-iodo-4-meth-
with various aryl halides and gave the corresponding products oxybenzene suggests that the reaction proceeds by oxidative
in 78–83% yield. It was observed that aryl halides having elec- addition followed by reductive elimination. In addition to this,
tron withdrawing groups showed greater reactivity and gave the order of reactivity suggests that aryl halides having electron
good yield of products compared to aryl halides having elec- withdrawing groups stabilize the transition state which corres-
Table 3: C-arylation of acetylacetone using different aryl halidesa
Entry Aryl halide
Product
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
iodobenzene
3-phenylpentane-2,4-dione
8
10
6
80
79
83
78
81
76
75
bromobenzene
3-phenylpentane-2,4-dione
p-nitroiodobenzene
3-(4-nitrophenyl)-pentane-2,4-dione
3-p-tolylpentane-2,4-dione
p-methyliodobenzene
m-trifluoromethyliodobenzene
1-iodo-2-methylbenzene
1-iodo-4-methoxybenzene
10
7
3-(3-trifluromethyl-phenyl)-pentane-2,4-dione
3-o-tolyl-pentane-2,4-dione
11
12
3-(4-methoxy-phenyl)-pentane-2,4-dione
aReaction conditions: acetylacetone (3 mmol), aryl halide (1 mmol), 10 mol % CuO-nanoparticles, Cs2CO3 (0.5 mmol), DMSO; temperature 80 °C; N2; 1
atm.
bIsolated and optimized yields.
Page 3 of 6
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 35.
Table 4: C-arylation of diethyl malonate using different aryl halidesa.
Entry Aryl halide
Product
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
iodobenzene
2-phenylmalonic acid diethylester
9
11
6
78
76
81
76
80
75
74
bromobenzene
2-phenylmalonic acid diethylester
p-nitroiodobenzene
2-(4-nitrophenyl)-malonic acid diethylester
2-p-tolylmalonic acid diethylester
p-methyliodobenzene
m-trifluoromethyliodobenzene
1-iodo-2-methylbenzene
1-iodo-4-methoxybenzene
12
7
2-(3-trifluromethyl-phenyl)-malonic acid diethylester
2-o-tolylmalonic acid diethylester
13
14
3-(4-methoxy-phenyl)-malonic acid diethylether
aReaction conditions: diethyl malonate (3 mmol), aryl halide (1 mmol), 10 mol % CuO-nanoparticles, Cs2CO3 (0.5 mmol), DMSO; temperature 80 °C;
N2; 1 atm.
bIsolated and optimized yields.
ponds to good yields with a short reaction time in comparison to
Table 5: Recycle studies of nano-CuO for C-arylation reactiona.
aryl halides having electron donating groups (Figure 2).
Run
Time (h)
Yieldb (%)
The reaction was then carried out with recycled catalyst. The
CuO-nanoparticles were recovered by centrifugation of the
reaction mixture and washed thoroughly with ethyl acetate. The
resulting nanoparticles could be reused for several cycles
without any significant loss of activity. In our study, we used
same nanoparticles three times and the results are summarized
below (Table 5). The TEM and XRD analysis of recycled CuO-
nanoparticles, after the fourth run showed that particles are
identical in shape and size, hence CuO-nanoparticles are
unchanged during the reaction (Figure 3).
1
2
3
4
8
8
8
8
80
78
77
76
aReaction conditions: acetylacetone (3 mmol), iodobenzene (1 mmol),
0 mol % CuO-nanoparticles, Cs2CO3 (0.5 mmol), DMSO; temperature
0 °C; N2; 1atm.
1
8
bIsolated and optimized yields.
ates (Table 4) has been developed using CuO-nanoparticles as
the catalyst. The products were obtained in moderate to good
Conclusion
An efficient, facile and economical method for synthesis of yields and the catalyst can be recycled up to four cycles with
3
-arylpentane-2,4-diones (Table 3) and diethyl 2-aryl-malon- almost consistent activity. The present protocol represents a
simple and remarkably active catalytic system to catalyze
Ullmann-type C–C bond formation, which potentially offers an
efficient protocol for accessing a variety of α-arylated dicar-
bonyl compounds.
Experimental
General
The materials were purchased from Sigma-Aldrich and Merck
and were used without further purification. Mass spectra were
recorded in a TOF-mass spectrometer model no. KC455. 1H
NMR and 13C NMR spectra were recorded on a Bruker spectro-
spin at 300 MHz and 75 MHz, respectively. All 1H NMR and
1
3C NMR spectra were run in CDCl3 and chemical shifts are
expressed as ppm relative to internal Me4Si. Elemental analyses
were performed using Heraeus CHN-Rapid Analyzer. Powder
X-ray diffraction measurements were carried out on a Bruker
D8 Discover HR-XRD instrument using Cu Kα radiation (λ =
1.54184 Å).
Figure 2: Proposed reaction pathway for the CuO-nanoparticles cata-
lyzed C–C coupling reaction.
Page 4 of 6
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 35.
Figure 3: Powder X-ray diffraction pattern and TEM image of recycled CuO-nanoparticles.
Experimental Section
References
CuO-nanoparticles (10 mol %) were added to the mixture of
iodobenzene (1 mmol), acetylactone (3 mmol) and (0.5 mmol)
of Cs2CO3 in DMSO (2 ml) under nitrogen atmosphere. The
resulting reaction mixture was stirred at 80 °C for 8 h. Progress
of the reaction was continuously monitored by TLC. After
completion of reaction, the catalyst was recovered by centrifu-
gation. The nanoparticles, were first washed with distilled meth-
anol to remove some of the Cs2CO3, then several times with
ethyl acetate and dried in an oven overnight at 150 °C. The
filtrate was poured into 1N HCl and extracted with EtOAc. The
combined organic layers were washed with brine, dried over
anhydrous Na2SO4 and concentrated at reduced pressure. The
residue was chromatographed to afford pure 3-phenyl-2,4-
pentadione (Entry 1, Table 3). From the spectral data it was
observed that some products show 1,3-keto-enol tautomerism.
The structures of all the products were unambiguously estab-
lished on the basis of their spectral properties (1H NMR, MS
and 13C NMR).
1. Ren, T. Chem. Rev. 2008, 108, 4185–4207. doi:10.1021/cr8002592
2.
3.
4.
5.
6.
7.
Hart, D. J. Science 1984, 223, 883–887.
doi:10.1126/science.223.4639.883
Iwama, T.; Rawal, V. H. Org. Lett. 2006, 8, 5725–5728.
doi:10.1021/ol062093g
Ramthoul, Y. K.; Chartrand, A. Org. Lett. 2007, 9, 1029–1032.
doi:10.1021/ol063057k
Masselot, D.; Charmant, J. P. H.; Gallagher, T. J. Am. Chem. Soc.
2006, 128, 694–695. doi:10.1021/ja056964d
Wu, J. Y.; Nie, L.; Luo, J.; Dai, W.-M. Synlett 2007, 2728–2732.
doi:10.1055/s-2007-991053
Kamikawa, K.; Takemoto, I.; Takemoto, S.; Matsuzaka, H.
J. Org. Chem. 2007, 72, 7406–7408. doi:10.1021/jo0711586
8. Wright, J. B. J. Org. Chem. 1964, 29, 1905–1909.
doi:10.1021/jo01030a059
9.
Beare, N. A.; Hartwig, J. F. J. Org. Chem. 2002, 67, 541–555.
doi:10.1021/jo016226h
10.You, J.; Verkade, J. G. Angew. Chem. 2003, 42, 5051–5053.
doi:10.1002/anie.200351954
11.Thathagar, M. B.; Rothenberg, G. Org. Biomol. Chem. 2006, 4,
11–115. doi:10.1039/b513450a
2.Thathagar, M. B.; Beckers, J.; Rothenberg, G. Green Chem. 2004, 6,
15–218. doi:10.1039/b401586j
1
1
2
Supporting Information
13.Suzuki, H.; Kobayashi, T.; Osuka, A. Chem. Lett. 1983, 12, 589–590.
doi:10.1246/cl.1983.589
Supporting Information File 1
Typical procedure and characterization data of prepared
compounds
14.Setsune, J.-I.; Matsukawa, K.; Wakemoto, H.; Kitao, T. Chem. Lett.
1981, 10, 367–370. doi:10.1246/cl.1981.367
1
1
1
1
1
5.Jiang, Y.; Wu, N.; Wu, H.; He, M. Synlett 2005, 2731–2734.
doi:10.1055/s-2005-918921
[http://www.beilstein-journals.org/bjoc/content/
6.Yip, S. F.; Cheung, H. Y.; Zhou, Z.; Kwong, F. Y. Org. Lett. 2007, 9,
supplementary/1860-5397-6-35-S1.pdf]
3
469–3472. doi:10.1021/ol701473p
7.Fox, J. M.; Huang, X.; Chieffi, A.; Buchwald, S. L. J. Am. Chem. Soc.
000, 122, 1360–1370. doi:10.1021/ja993912d
2
8.Culkin, D. A.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 5816–5817.
doi:10.1021/ja015732l
Acknowledgements
Saurav Bhardwaj and Roona Poddar thank CSIR, New Delhi for
9.Li, P.; Wang, L.; Li, H. Tetrahedron 2005, 61, 8633–8640.
doi:10.1016/j.tet.2005.07.013
providing a fellowship.
Page 5 of 6
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 35.
2
0.Okuro, K.; Furuune, M.; Miura, M.; Nomura, M. J. Org. Chem. 1993,
8, 7606–7607. doi:10.1021/jo00078a053
5
2
1.Lucas, E.; Decker, S.; Khaleel, A.; Seitz, A.; Fultz, S.; Ponce, A.; Li, W.;
Carnes, C.; Klabunde, K. J. Chem.–Eur. J. 2001, 7, 2505–2510.
doi:10.1002/1521-3765(20010618)7:12<2505::AID-CHEM25050>3.0.C
O;2-R
2
2
2
2
2
2
2.Jiang, Y.; Decker, S.; Mohs, C.; Klabunde, K. J. J. Catal. 1998, 180,
24–35. doi:10.1006/jcat.1998.2257
3.Larsson, P.-O.; Andersson, A. J. Catal. 1998, 179, 72–89.
doi:10.1006/jcat.1998.2198
4.Rout, L.; Jammi, S.; Punniyamurthy, T. Org. Lett. 2007, 9, 3397–3399.
doi:10.1021/ol0713887
5.Kantam, M. L.; Laha, S.; Yadav, J.; Bhargava, S. Tetrahedron Lett.
2008, 49, 3083–3086. doi:10.1016/j.tetlet.2008.03.053
6.Chikán, V.; Molnár, Á.; Belázsik, K. J. Catal. 1999, 184, 134–143.
doi:10.1006/jcat.1999.2437
7.Kantam, M. L.; Yadav, J.; Laha, S.; Sreedhar, B.; Jha, S.
Adv. Synth. Catal. 2007, 349, 1938–1942.
doi:10.1002/adsc.200600483
2
2
3
3
3
8.Rout, L.; Sen, T. K.; Punniyamurthy, T. Angew. Chem., Int. Ed. 2007,
46, 5583–5586. doi:10.1002/anie.200701282
9.Kidwai, M.; Poddar, R.; Mothsra, P. Beil. J. Org. Chem. 2009, 5,
No. 10. doi:10.3762/bjoc.5.10
0.Kidwai, M.; Poddar, R.; Diwaniyan, S.; Kuhad, R. C. Adv. Synth. Catal.
2
009, 351, 589–595. doi:10.1002/adsc.200800611
1.Kidwai, M.; Bhatnagar, D.; Mishra, N. K.; Bansal, V. Catal. Commun.
008, 9, 2547–2549. doi:10.1016/j.catcom.2008.07.010
2
2.Kidwai, M.; Bhardwaj, S.; Mishra, N. K.; Bansal, V.; Kumar, A.;
Mozumdar, S. Catal. Commun. 2009, 10, 1514–1517.
doi:10.1016/j.catcom.2009.04.006
33.Kidwai, M.; Bansal, V.; Kumar, A.; Mozumdar, S. Green Chem. 2007,
9, 742–745. doi:10.1039/b702287e
3
4.Kidwai, M.; Mishra, N. K.; Bansal, V.; Kumar, A.; Mozumdar, S.
Tetrahedron Lett. 2007, 48, 8883–8887.
doi:10.1016/j.tetlet.2007.10.050
35.Gonzalez-Arellano, C.; Luque, G.; Macquarrie, D. J. Chem. Commun.
2009, 1410–1412. doi:10.1039/b818767c
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.6.35
Page 6 of 6
(page number not for citation purposes)