CuO nanoparticles catalyzed C-N, C-O, and C-S cross-coupling reactions: Scope and mechanism

Article abstract of DOI:10.1021/jo8024253

CuO nanoparticles have been studied for C-N, C-O, and C-S bond formations via cross-coupling reactions of nitrogen, oxygen, and sulfur nucleophiles with aryl halides. Amides, amines, imidazoles, phenols, alcohols and thiols undergo reactions with aryl iodides in the presence of a base such as KOH, Cs ₂CO₃, and K₂CO₃ at moderate temperature. The procedure is simple, general, ligand-free, and efficient to afford the cross-coupled products in high yield.

Full text of DOI:10.1021/jo8024253

CuO Nanoparticles Catalyzed C-N, C-O, and C-S Cross-Coupling
Reactions: Scope and Mechanism
Suribabu Jammi, Sekarpandi Sakthivel, Laxmidhar Rout, Tathagata Mukherjee,
Santu Mandal, Raja Mitra, Prasenjit Saha, and Tharmalingam Punniyamurthy*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India
tpunni@iitg.ernet.in
ReceiVed October 31, 2008
CuO nanoparticles have been studied for C-N, C-O, and C-S bond formations via cross-coupling
reactions of nitrogen, oxygen, and sulfur nucleophiles with aryl halides. Amides, amines, imidazoles,
phenols, alcohols and thiols undergo reactions with aryl iodides in the presence of a base such as KOH,
Cs2CO3, and K2CO3 at moderate temperature. The procedure is simple, general, ligand-free, and efficient
to afford the cross-coupled products in high yield.
Introduction
on the use of iron-12 and nickel-based13 catalytic systems for
this purpose. Most of the systems involve a homogeneous
process, and the ligand chelated with the metal plays a crucial
role in the catalysis.
Nanomaterials containing high surface area and reactive
morphologies have been studied as effective catalysts for organic
synthesis.8k,11k,14 Furthermore, the nanomaterial catalyzed reac-
tions provide the advantages of high atom efficiency, simplified
isolation of product, and easy recovery and recyclability of the
catalysts. In preliminary communication, we reported the
catalysis of CuO nanoparticles for the cross-coupling reactions
of amines8k and thiols11k with iodobenzene. The reactions were
simple, general, and ligand-free, and the CuO nanoparticles were
recyclable. These features led us to further study the scope of
The formation of C-N, C-O, and C-S bonds is prevalent
in numerous compounds that are of biological, pharmaceutical,
and material interest (Figure 1).1 One of the most common
synthetic methods for their preparation is the copper-assisted
classic Ullmann reaction. However, these reactions often require
harsh conditions such as high temperature (>200 °C) and
stoichiometric or greater amount of copper reagent, which on
scale-up leads to problem of waste disposal.2 To overcome these
limitations, much attention has been recently focused to develop
catalytic systems to reduce the environmental impact (E-factor)
of the processes.3,4 Palladium5-7 and copper8-11 complexes
containing electron-rich ligands have been studied considerably
for the cross-coupling of nitrogen, oxygen, and sulfur nucleo-
philes with aryl halides. Subsequently, few studies have focused
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Lett. 1983, 927. (b) Louie, J.; Hartwig, J. F. Tetrahedron Lett. 1995, 36, 3609.
(c) Ali, M. H.; Buchwald, S. L. J. Org. Chem. 2001, 66, 2560. (d) Huang, X.;
Anderson, K. W.; Zim, D.; Jiang, L.; Klapars, A.; Buchwald, S. L. J. Am. Chem.
Soc. 2003, 125, 6653. (e) Gajare, A. S.; Toyota, K.; Yoshifuji, M.; Ozawa, F. J.
Org. Chem. 2004, 69, 6504. (f) Beletskaya, I. P.; Bessmertnykh, A. G.; Averin,
A. D.; Denat, F.; Guilard, R. Eur. J. Org. Chem. 2005, 261. (g) Wolfe, J. P.;
Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org. Chem. 2000, 65,
1158. (h) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144. (i) Dai,
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13001.
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J. Am. Chem. Soc. 1997, 119, 3395. (b) Mann, G.; Hartwig, J. F. Tetrahedron
Lett. 1997, 38, 8005. (c) Mann, G.; Incarvito, C.; Rheingold, A. L.; Hartwig,
J. F. J. Am. Chem. Soc. 1999, 121, 3224. (d) Aranyos, A.; Old, D. W.; Kiyomori,
A.; Wolfe, J. P.; Sadighi, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121,
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2000, 122, 10718. (f) Torraca, K. E.; Huang, X.; Parrish, C. A.; Buchwald, S. L.
J. Am. Chem. Soc. 2001, 123, 10770.
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10.1021/jo8024253 CCC: $40.75
Published on Web 01/27/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 1971–1976 1971

Jammi et al.
TABLE 1. Reactions of Benzamide, Aniline, Phenol and
Thiophenol with Aryl Halides, Phenyl Tosylate, and Phenylboronic
Acid
FIGURE 1. Examples for biologically active compounds.
the CuO nanoparticles for the catalysis of the C-N, C-O, and
C-S cross-coupling reactions. Here we report the reactions of
amides, amines, imidazoles, phenols, alcohols, and thiols with
aryl iodides. The reactions of bromobenzene, chlorobenzene,
phenyl tosylate, and phenylboronic acid are also studied, but
those are found to be inferior to that of aryl iodides, leading to
the cross-coupled products in lower yield.
Results and Discussion
The cross-coupling reactions of benzamide, aniline, phenol,
and thiophenol with aryl halides and their analogues were
studied as model substrates (Table 1). We were pleased to find
that the reactions occurred to afford the corresponding cross-
coupled products in high yield. The C-N cross-coupling
reactions were effective under air, and the C-S and C-O cross-
couplings provided the best results in nitrogen atmosphere.15
Iodobenzene exhibited greater reactivity compared to that of
phenylboronic acid and bromobenzene. Under these conditions,
chlorobenzene and phenyl tosylate were less reactive, affording
the cross-coupled products in <5% yield. The C-N cross-
coupling reactions were effective in a 1:3 mixture of DMSO/
t-BuOH, while DMSO was found to be the solvent of choice
for the C-O and C-S cross-coupling reactions. The reactions
were free from the formation of homocoupled biaryl compound,
a CuO nanoparticles (5 mol %), amide/aniline (1.2 mmol), aryl halide/
phenylboronic acid/phenyl tosylate (1 mmol), and KOH (1.5 mmol)
were stirred at 110 °C in a 1:3 mixture of dry DMSO:t-BuOH under air.
b CuO nanoparticles (2.5 mol %), phenol (1 mmol), aryl halide/
phenylboronic acid/phenyl tosylate (1.2 mmol), and KOH (1.5 mmol)
were stirred at 110 °C in dry DMSO (1 mL) under N2 atmosphere.
c CuO nanoparticles (2.5 mol %), thiol (1 mmol), aryl halide/
phenylboronic acid/phenyl tosylate (1.2 mmol), and KOH (1.5 mmol)
were stirred at 80 °C in dry DMSO (1 mL) under N2 atmosphere.
(7) For C-S couplings, see: (a) Li, G. Y.; Zheng, G.; Noonan, A. F. J. Org.
Chem. 2001, 66, 8677. (b) Mispelaere-Canivet, C.; Spindler, J.-F.; Perrio, S.;
Beslin, P. Tetrahedron 2005, 61, 5253. (c) Itoh, T.; Mase, T. Org. Lett. 2004, 6,
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7397. (f) Schopfer, U.; Schlapbach, A. Tetrahedron 2001, 57, 3069. (g) Li, G. Y.
Angew. Chem., Int. Ed. 2001, 40, 1513. (h) Barbieri, R. S.; Bellato, C. R.; Dias,
A. K. C.; Massabni, A. C. Catal. Lett. 2006, 109, 171. (i) Dickens, M. J.; Gilday,
J. P.; Mowlem, T. J.; Widdowson, D. A. Tetrahedron 1991, 47, 8621. (j)
Ishiyama, T.; Mori, M.; Suzuki, A.; Miyaura, N. J. Organomet. Chem. 1996,
525, 225. (k) Zheng, N.; McWilliams, J. C.; Fleitz, F. J.; Armstrong, J. D.;
Volante, R. P. J. Org. Chem. 1998, 63, 9606. (l) Mann, G.; Baranano, D.;
Hartwig, J. F.; Rheingold, A. L.; Guzei, I. A. J. Am. Chem. Soc. 1998, 120,
9205.
(8) For N-arylation of amines, see: (a) Gujadhur, R. K.; Bates, C. G.;
Venkataraman, D. Org. Lett. 2001, 3, 4315. (b) Zhang, H.; Cai, Q.; Ma, D. J.
Org. Chem. 2005, 70, 5164. (c) Rao, H.; Jin, Y.; Fu, H.; Jiang, Y.; Zhao, Y.
Chem. Eur. J. 2006, 12, 3636. (d) Kwong, F. Y.; Klapars, A.; Buchwald, S. L.
Org. Lett. 2002, 4, 581. (e) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2003, 5,
793. (f) Shafir, A.; Lichtor, P. A.; Buchwald, S. L. J. Am. Chem. Soc. 2007,
129, 3490. (g) Ma, D.; Zhang, Y.; Yao, J.; Wu, S.; Tao, F. J. Am. Chem. Soc.
1998, 120, 12459. (h) Yang, M.; Liu, F. J. Org. Chem. 2007, 72, 8969. (i)
Nandurkar, N. S.; Bhanushali, M. J.; Bhor, M. D.; Bhanage, B. M. Tetrahedron
Lett. 2007, 48, 6573. (j) Shafir, A.; Buchwald, S. L. J. Am. Chem. Soc. 2006,
128, 8742. (k) Rout, L.; Jammi, S.; Punniyamurthy, T. Org. Lett. 2007, 9, 3397.
and the controlled experiments without CuO nanoparticles
showed no reaction.
Reactions of Amides, Amines and Imidazoles. The C-N
cross-coupling reactions of benzamide, p-toluenesulfonamide,
oxazolidinone, and hexanoamide with aryl iodides were inves-
tigated (Table 2). The reactions with iodobenzene occurred to
give the cross-coupled products in 45-88% yield, whereas
4-nitro-1-iodobenzene showed greater reactivity compared to
that of 4-methoxy-1-iodobenzene. These reactions could be
performed in the presence of either K2CO3 or Cs2CO3 as a base
in moderate to good yield. Reactions of substituted aryl iodides
with amines and imidazoles were further studied (Table 3).
1972 J. Org. Chem. Vol. 74, No. 5, 2009

CuO Nanoparticles Catalyzed Cross-Coupling Reactions
TABLE 2. CuO Nanoparticles Catalyzed Amidation of Aryl Iodides
a CuO nanoparticles (5 mol %), amide (1.2 mmol), aryl iodide (1 mmol), and KOH (1.5 mmol) were stirred at 110 °C in a 1:3 mixture of dry DMSO/
t-BuOH (1 mL). b Cs2CO3 (1.5 mmol) used. c K2CO3 (1.5 mmol) used. d CuO nanoparticles (10 mol %) used.
Imidazole, 2-methylimidazole, benzimidazole, and aniline un-
derwent reactions with up to 89% yield. The reactions were
clean, and no byproduct was observed.
Reactions of Phenols, Naphthols, and Alcohols. Next, the
C-O cross-coupling reactions of the hydroxy compounds with
aryl iodides were studied. Phenols having 2-t-Bu, 2-Me, 2-OMe,
3-Me, 3-NO2, 4-t-Bu, 4-Me, 4-OMe, 4-NO2, 2,4-di-t-Bu, and
2,4-di-Me groups, 1-naphthol, 2-naphthol, and 1-decanol with
iodobenzene underwent reaction to give the corresponding C-O
cross-coupled products in high yield (Table 4). These hydroxy
compounds with bromobenzene were further investigated by
increasing the catalyst to 5 mol % and the temperature to 120
°C to give the C-O cross-coupled products in moderate yield.
The substrate having an electron-donating group showed greater
reactivity compared to those with electron-withdrawing groups.
Under these reaction conditions, polyhydroxy compounds,
pentaerythritol, and triethanolamine with iodobenzene provided
the corresponding polyaryl ether in excellent yield (eqs 1 and
2). To study the effect of substituent, phenol with aryl iodides
having 3-NO2, 4-NO2, 4-Me, 2- OMe, 4-OMe, and 2,4-di-Me
substituents were further examined (Table 5). As above, the
(9) For N-arylation of amides, imidazoles, and N-heterocycles, see: (a)
Kiyomori, A.; Marcoux, J.-F.; Buchwald, S. L. Tetrahedron Lett. 1999, 40, 2657.
(b) Klapars, A.; Antilla, J. C.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc.
2001, 123, 7727. (c) Antilla, J. C.; Baskin, J. M.; Barder, T. E.; Buchwald, S. L.
J. Org. Chem. 2004, 69, 5578. (d) Cristau, H.-J.; Cellier, P. P.; Spindler, J.-F.;
Taillefer, M. Eur. J. Org. Chem. 2004, 695. (e) Pan, X.; Cai, Q.; Ma, D. Org.
Lett. 2004, 6, 1809. (f) Klapars, A.; Huang, X.; Buchwald, S. L. J. Am. Chem.
Soc. 2002, 124, 7421. (g) Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L.
J. Am. Chem. Soc. 2005, 127, 4120. (h) Hosseinzadeh, R.; Tajbakhsh, M.;
Mohadjerani, M.; Mehdinejad, H. Synlett 2004, 1517. (i) Guo, X.; Rao, H.; Fu,
H.; Jiang, Y.; Zhao, Y. AdV. Synth. Catal. 2006, 348, 2197. (j) Deng, W.; Wang,
Y.-F.; Zou, Y.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2004, 45, 2311. (k) Cristau,
H,-J.; Cellier, P. P.; Spindler, J.-F.; Taillefer, M. Chem. Eur. J. 2004, 10, 5607.
(l) Moriwaki, K.; Satoh, K.; Takada, M.; Ishino, Y.; Ohno, T. Tetrahedron Lett.
2005, 46, 7559. (m) Huang, Y.-Z.; Gao, J.; Ma, H.; Miao, H.; Xu, J. Tetrahedron
Lett. 2008, 49, 948. (n) Ma, H.-C.; Jiang, X.-Z. J. Org. Chem. 2007, 72, 8943.
(o) Mao, J.; Guo, J.; Song, H.; Ji, S.-J. Tetrahedron 2008, 64, 1383. (p) Altman,
R. A.; Koval, E. D.; Buchwald, S. L. J. Org. Chem. 2007, 72, 6190. (q) Verma,
A. K.; Singh, J.; Sankar, V. K.; Chaudhary, R.; Chandra, R. Tetrahedron Lett.
2007, 48, 4207. (r) Altman, R. A.; Buchwald, S. L. Org. Lett. 2006, 8, 2779.
(10) For C-O couplings, see: (a) Marcoux, J.-F.; Doye, S.; Buchwald, S. L.
J. Am. Chem. Soc. 1997, 119, 10539. (b) Wolter, M.; Nordmann, G.; Job, G. E.;
Buchwald, S. L. Org. Lett. 2002, 4, 973. (c) Altman, R. A.; Shafir, A.; Choi, A.;
Lichtor, P. A.; Buchwald, S. L. J. Org. Chem. 2008, 73, 284. (d) Buck, E.;
Song, Z. J.; Tschaen, D.; Dormer, P. G.; Volante, R. P.; Reider, P. J. Org. Lett.
2002, 4, 1623. (e) Lv, X.; Bao, W. J. Org. Chem. 2007, 72, 3863. (f) Ma, D.;
Cai, Q. Org. Lett. 2003, 5, 3799. (g) Cristau, H.-J.; Cellier, P. P.; Hamada, S.;
Spindler, J.-F.; Taillefer, M. Org. Lett. 2004, 6, 913. (h) Ouali, A.; Spindler,
J.-F.; Cristau, H.-J.; Taillefer, M. AdV. Synth. Catal. 2006, 348, 499. (i) Palomo,
C.; Oiarbide, M.; Lopez, R.; Gomez-Bengoa, E. Chem. Commun. 1998, 2091.
(j) Fagan, P. J.; Hauptman, E.; Shapiro, R.; Casalnuovo, A. J. Am. Chem. Soc.
2000, 122, 5043. (k) Benyahya, S.; Monnier, F.; Taillefer, M.; Wong Chi Man,
M.; Bied, C.; Ouazzani, F. AdV. Synth. Catal. 2008, 350, 2205.
J. Org. Chem. Vol. 74, No. 5, 2009 1973

Jammi et al.
TABLE 3. CuO Nanoparticles Catalyzed Reactions of Imidazoles,
Indole, and Aniline with Aryl Iodides
TABLE 4. CuO Nanoparticles Catalyzed C-O Cross-Coupling of
Substituted Phenols, 1-Naphthol, 2-Naphthol, and Decanol with
Iodo- and Bromobenzene
a CuO nanoparticles (5 mol %), substrate (1.2 mmol), aryl iodide (1
mmol), and KOH (1.5 mmol) were stirred at 110 °C in a 1:3 mixture of
dry DMSO/t-BuOH (1 mL). b CuO nanoparticles (10 mol %) used.
reactions occurred to afford the C-O cross-coupled products
in 70-98% yield.
a CuO nanoparticles (2.5 mol %), ROH (1 mmol), iodobenzene (1.2
mmol), and KOH (1.5 mmol) were stirred at 110 °C in dry DMSO (1
mL) under N2 atmosphere. b CuO nanoparticles (5 mol %),
bromobenzene (1.2 mmol), and temperature of 120 °C were used.
1-naphthyl iodide showed moderate reactivity, leading to the
cross-coupled product in 38% yield.
Reactions of Thiols. Finally, the C-S cross-coupling reac-
tions of thiols with aryl iodides were studied (Table 6).
Thiophenol and 4-methylthiophenol were investigated as rep-
resentative examples with aryl iodides having 3-NO2, 4-NO2,
4-Br, 4-Me, 4-OMe, and 2,4-di-Me substituents. The reactions
occurred efficiently to afford the C-S cross-coupled products
with up to 96% yield. Under these conditions, thiophenol with
Mechanism. The enhanced reactivity of the aryl iodide
having an electron-withdrawing group compared to that with
an electron-donating group suggests that the reactions occur via
oxidative addition followed by a reductive elimination process.
The reactions are heterogeneous, and no leaching of the metal
species is involved.4i,16 To reveal that, the CuO nanoparticles
were stirred at 110 °C for 24 h in DMSO in the presence as
(11) For C-S couplings, see: (a) Bates, C. G.; Gujadhur, R. K.; Venkataraman,
D. Org. Lett. 2002, 4, 2803. (b) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2002,
4, 3517. (c) Wu, Y.-J.; He, H. Synlett 2003, 1789. (d) Bates, C. G.; Saejueng,
P.; Doherty, M. Q.; Venkataraman, D. Org. Lett. 2004, 6, 5005. (e) Deng, W.;
Zou, Y.; Wang, Y.-F.; Liu, L.; Guo, Q.-X. Synlett 2004, 1254. (f) Palomo, C.;
Oiarbide, M.; Lopez, R.; Gomez-Bengoa, E. Tetrahedron Lett. 2000, 41, 1283.
(g) Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2002, 4, 4309. (h)
Herradura, P. S.; Pendola, K. A.; Guy, R. K. Org. Lett. 2000, 2, 2019. (i) Zhu,
D.; Xu, L.; Wu, F.; Wan, B. Tetrahedron Lett. 2006, 47, 5781. (j) Sperotto, E.;
van Klink, G. P. M.; de Vries, J. G.; van Koten, G. J. Org. Chem. 2008, 73,
5625. (k) Rout, L.; Sen, T. K.; Punniyamurthy, T. Angew. Chem., Int. Ed. 2007,
46, 5583. (l) Rout, L.; Saha, P.; Jammi, S.; Punniyamurthy, T. Eur. J. Org.
Chem. 2008, 640.
(12) (a) Correa, A.; Bolm, C. Angew. Chem., Int. Ed. 2007, 46, 8862. (b)
Correa, A.; Elmore, S.; Bolm, C. Chem. Eur. J. 2008, 14, 3527. (c) Correa, A.;
Carril, M.; Bolm, C. Angew. Chem., Int. Ed. 2008, 47, 2880. (d) Bistri, O.; Correa,
A.; Bolm, C. Angew. Chem., Int. Ed. 2008, 47, 586. (e) Bonnamour, J.; Bolm,
C. Org. Lett. 2008, 10, 2665.
(13) For C-N couplings, see: (a) Wolfe, J. P.; Buchwald, S. L. J. Am. Chem.
Soc. 1997, 119, 6054. (b) Brenner, E.; Fort, Y. Tetrahedron Lett. 1998, 39, 5359.
(c) Lipshutz, B. H.; Ueda, H. Angew. Chem., Int. Ed. 2000, 39, 4492. (d)
Desmarets, C.; Schneider, R.; Fort, Y. J. Org. Chem. 2002, 67, 3029. For C-S
coupling see: (e) Cristau, H. J.; Chabaud, B.; Chene, A.; Christol, H. Synthesis
1981, 892. (f) Percec, V.; Bae, J.-Y.; Hill, D. H. J. Org. Chem. 1995, 60, 6895.
(g) Takagi, K. Chem. Lett. 1987, 2221. (h) Jammi, S.; Barua, P.; Rout, L.; Saha,
P.; Punniyamurthy, T. Tetrahedron Lett. 2008, 49, 1484.
1974 J. Org. Chem. Vol. 74, No. 5, 2009

CuO Nanoparticles Catalyzed Cross-Coupling Reactions
TABLE 5. CuO Nanoparticles Catalyzed C-O Cross-Coupling of
Phenol with Substituted Aryl Iodides
TABLE 6. CuO Nanoparticles Catalyzed C-S Cross-Coupling of
Thiols with Aryl Iodides
a CuO nanoparticles (2.5 mol %), phenol (1 mmol), aryl iodide (1.2
mmol), and KOH (1.5 mmol) were stirred at 110 °C in dry DMSO (1
mL) under N2 atmosphere.
well as in the absence of KOH. The catalyst was then separated
by centrifugation, and the solutions were independently studied
at 110 °C for the C-O cross-coupling reaction of phenol with
iodobenzene in the presence of KOH under nitrogen atmosphere.
Both experiments showed no reaction, and the starting materials
were recovered intact. In addition, the TEM analysis of the CuO
nanoparticles, before and after the reaction, showed identical
particle shape and size (Figure 2). Likewise, the powder X-ray
diffraction analysis exhibited identical peaks for both the fresh
and recovered CuO nanoparticles (Figure 3).17 These experi-
mental results clearly suggest that the reaction involves a
heterogeneous process and the catalysis may occur on the
surface of the CuO nanoparticles. Thus, the DMSO-stabilized
CuO nanoparticles a may undergo reaction with aryl halide to
a CuO nanoparticles (2.5 mol %), thiol (1 mmol), aryl iodide (1.2
mmol), and KOH (1.5 mmol) were stirred at 80 °C in dry DMSO (1
mL) under N2 atmosphere. b Catalyst (5 mol %) used.
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FIGURE 2. TEM images of (a) fresh CuO nanoparticles and (b) CuO
nanoparticles after the third catalytic cycle.
give intermediate b where the excess positive charge generated
could be shared among the CuO nanoparticles present on the
surface of the cluster (Scheme 1). The latter b may then undergo
reaction with nucleophile to give intermediate c that can
complete the catalytic cycle by reductive elimination of the
cross-coupled product.
(15) The C-S and C-O cross-coupling reactions under air provided disulfide
and quinone, respectively, as byproducts.
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J. Org. Chem. Vol. 74, No. 5, 2009 1975

Jammi et al.
conditions. The catalyst is recyclable, and a variety of substrates
undergo reaction in high yield.
Experimental Section
General Procedure for C-N Cross-Coupling Reactions.
Nitrogen nucleophile (1.2 mmol), aryl iodide (1 mmol), CuO
nanoparticles (5 mol %), and KOH (1.5 mmol) were stirred at 110
°C in a 1:3 mixture of dry DMSO/t-BuOH (1 mL). The progress
of the reaction was monitored by TLC using EtOAc and hexane as
eluent. After completion, the reaction mixture was treated with
EtOAc (10 mL) and water (3 mL). The organic layer was separated,
and the aqueous layer was extracted with EtOAc (3 × 5 mL). The
combined organic solution was washed with brine (3 × 5 mL) and
water (1 × 5 mL). Drying (Na2SO4) and evaporation of the solvent
provided a residue, which was purified on short pad of silica gel
using EtOAc and hexane as eluent.
FIGURE 3. Powder X-ray diffraction patterns of (a) fresh CuO
nanoparticles and (b) CuO nanoparticles after the third catalytic cycle.
SCHEME 1. Proposed Mechanism for CuO Nanoparticles
Catalyzed Cross-Coupling Reactions
N-Phenylbenzamide. (Table 2, entry 1).12b Colorless solid; yield
74%; mp 163 °C (lit.18 162-163 °C); 1H NMR (400 MHz, CDCl3)
δ 7.84 (d, J ) 7.2 Hz, 2H), 7.78 (s, 1H), 7.61 (d, J ) 8.0 Hz, 2H),
7.52 (d, J ) 7.6 Hz, 1H), 7.47 (t, J ) 8.0 Hz, 2H), 7.36 (t, J ) 8.0
Hz, 2H), 7.14 (t, J ) 7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
166.0, 138.1, 135.2, 132.0, 129.3, 129.0, 127.2, 124.8, 120.5; FT-
IR (KBr) 3310, 2995, 1659, 1604, 1533, 1420, 1315, 1233, 1185,
1090, 1023 cm-1. Anal. Calcd for C13H11NO: C, 79.16; H, 5.62;
N, 7.10. Found: C, 79.23; H, 5.65; N, 7.06.
General Procedure for C-O and C-S Cross-Coupling
Reactions. Oxygen or sulfur nucleophile (1 mmol), aryl iodide (1.2
mmol), CuO nanoparticles (2.5 mol %), and KOH (1.5 mmol) were
stirred at 80-110 °C in dry DMSO (1 mL) under N2 atmosphere.
Monitoring of the reaction, workup procedure, and purification of
the C-O and C-S cross-coupled products were performed as
described for the C-N cross-coupling reactions.
TABLE 7. Recyclability of the CuO Nanoparticles
1,1′-Oxy-bis-benzene. (Table 1, entry 3).8c Colorless liquid; yield
93%; 1H NMR (400 MHz, CDCl3) δ 7.33 (m, 4H), 7.12-7.08 (m,
2H), 7.00 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 157.4, 129.9,
123.4, 119.1; FT-IR (neat) 3038, 2910, 2864, 1583, 1484, 1456,
1254, 1216, 1161, 1138, 1017 cm-1. Anal. Calcd for C12H10O: C,
84.68; H, 5.92. Found: C, 84.66; H, 5.93.
run
catalyst recoverability (%)
product (conversion, %)c
1a
2b
3b
98
98
97
97
97
95
1-[(4-Methylphenyl)thio]-3-nitrobenzene. (Table 6, entry 8).
Yellow liquid; yield 65%; 1H NMR (400 MHz, CDCl3) δ 7.97-7.95
(m, 2H), 7.43-7.38 (m, 3H), 7.29-7.22 (m, 3H), 2.40 (s, 3H);13C
NMR (100 MHz, CDCl3) δ 143.6, 139.4, 134.3, 133.5, 132.6, 130.9,
129.7, 122.9, 122.4, 120.6, 21.5; FT-IR (neat) 3087, 2924, 2857,
1599, 1528, 1489, 1459, 1347, 1270, 1124, 1015 cm-1. Anal. Calcd
for C13H11NO2S: C, 63.65; H, 4.52; N, 5.71; S, 13.07. Found: C,
63.73; H, 4.55; N, 5.76; S, 13.10.
a CuO nanoparticles (2.5 mol %), phenol (1 mmol), iodobenzene (1.2
mmol), and KOH (1.5 mmol) were stirred for 15 h at 110 °C in dry
DMSO (1 mL) under N2 atmosphere. b Recovered catalyst used.
c
1
Determined from H NMR.
Recyclability Experiments. The CuO nanoparticles are
recyclable without loss of activity (Table 7). After completion
of the C-O cross-coupling of phenol with iodobenzene, the
reaction mixture was treated with water and EtOAc. The CuO
nanoparticles were recovered from the aqueous solution by
centrifugation. It was reused for the fresh C-O cross-coupling
of phenol with iodobenzene for three runs, and no loss of activity
was observed providing the cross-coupled product in high yield.
Acknowledgment. This work was supported by Department
of Science and Technology, New Delhi, and Council of
Scientific and Industrial Research, New Delhi. We thank Central
Instrumentation Facility (CIF) and Centre for Nanotechnology,
Indian Institute of Technology Guwahati, for TEM and powder
X-ray diffraction analysis.
Supporting Information Available: NMR (1H and 13C)
spectra of the cross-coupled products. This material is available
free of charge via the Internet at http://pubs.acs.org.
Conclusions
A simple, general, and efficient procedure is described for
the cross-coupling of nitrogen, oxygen, and sulfur nucleophiles
with aryl iodides using CuO nanoparticles under ligand-free
JO8024253
(18) Faler, C. A.; Jouille, M. M. Tetrahedron Lett. 2006, 47, 7229.
1976 J. Org. Chem. Vol. 74, No. 5, 2009