Reusable Cu2O-nanoparticle-catalyzed amidation of aryl iodides

Article abstract of DOI:10.1055/s-0029-1218368

The amidation of aryl iodides using Cu₂O nanoparticles is described. It is a heterogeneous process, no leaching of the Cu₂O species occurs, and the catalyst can be recovered and recycled without loss of activity. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1218368

LETTER
3323
Reusable Cu O-Nanoparticle-Catalyzed Amidation of Aryl Iodides
2
R
S
eusable Cu
O
u
-Nanopartic
r
les-Cata
i
lyzed
A
b
midation of
a
A
ryl Iodide
b
s
u Jammi, Sankarganesh Krishnamoorthy, Prasenjit Saha, Dipti S. Kundu, Sekarpandi Sakthivel,
2
Md Ashif Ali, Rajesh Paul, Tharmalingam Punniyamurthy*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India
Received 2 September 2009
OMe
OMe
Abstract: The amidation of aryl iodides using Cu O nanoparticles
2
is described. It is a heterogeneous process, no leaching of the Cu O
2
N
O
species occurs, and the catalyst can be recovered and recycled with-
out loss of activity.
MeO
MeO
O
F
N
H
Key words: Cu O nanoparticles, heterogeneous catalysis, cross-
N
2
O
N
coupling reaction, amide, aryl iodide
NH
O
O
N
NHAc
Transition-metal-catalyzed aryl–heteroatom bond forma-
tion by cross-coupling reaction constitutes a powerful
strategy for the synthesis of numerous compounds in bio-
tariquidar
P)g-yczprzteiꢀ iꢀhibitzr
(± ±)-iꢀeꢁz-id
aꢀtibiztic
Figure 1 Examples for biologically important molecules
1
logical, material, and pharmaceutical sciences. Among
them, the N-arylation of amides is of particular interest, as
The reaction conditions were optimized with benzamide
and 1-iodo-4-methylbenzene as the model substrates
their products contain structural motifs of many natural
products and biologically active molecules (Figure 1).2
(
Table 1). A series of reactions was performed in PEG
The most common synthetic method used for their prepa-
ration is the well-known classical Goldberg cross-cou-
having molecular weights of 200, 400, 1500, 4000, and
6000 with different bases and copper sources at varied
temperature. The best results were observed when the
reaction was carried out at 120 °C in the presence of 10
3
pling reaction. However, these reactions usually require
harsh conditions such as high temperature (>150 °C) and
stoichiometric amounts of copper that, on scale up, leads
to the problem of waste disposal. To overcome these
mol% CuI in PEG4000. Other systems such as PEG200
,
4
PEG400, PEG1500, and PEG6000 were inferior to PEG4000 by
either providing 4-methylphenol as byproduct or exhibit-
ing decreased reactivity. Among the bases, KOH was su-
drawbacks, palladium-based catalysts in the presence of
sterically hindered phosphines and copper-based5,6 cata-
lysts with electron-rich bidentate ligands have been sub-
ject to detailed study for amidation of aryl halides. These
are homogeneous processes and the ligands chelated with
the metals play a crucial role in the catalysis.
perior to NaOH, K CO , Cs CO , and K PO . The
2
3
2
3
3
4
reaction with CuI provided the best results in comparison
to commercial Cu O (<5 micron), CuO nanoparticles (ca.
2
a–c
3
3 nm),7 CuSO ·5H O, and CuCl ·2H O. Control ex-
4 2 2 2
The use of copper-based oxide nanoparticles for cross-
coupling reactions has attracted considerable interest in
periments without the copper source showed no reaction.
Similarly, bromobenzene and chlorobenzene exhibited no
reaction.
7
recent years. CuO nanoparticles have been used for the
cross-coupling of N-, O-, and S-nucleophiles with aryl ha-
7
a–7d
7e
7f
To study the scope of the protocol, the reactions of other
substrates were next investigated (Table 2). Benzamide
proceeded reaction with a series of aryl iodides to produce
the corresponding N-arylamides in 70–80% yield (entries
lides;
while Stille and Sonogashira reactions have
been studied using pre-prepared Cu O nanoparticles in
2
tetrabutylammonium bromide. These reactions provide
the advantages of atom efficiency, simplified product iso-
lation, and easy recovery and recyclability of the catalysts.
Herein, we wish to report the synthesis and application of
1
–7). Aryl iodides having electron-donating and -with-
drawing substituents were compatible affording the cross-
coupled products (entries 2–6). In addition, aliphatic
amides such as acetamide, hexanoamide, and 2-oxazoli-
dinone underwent reaction with iodobenzene to provide
the corresponding N-arylamides in 70–75% yield. Ali-
phatic amines exhibited greater reactivity compared to
aryl amides.
Cu O nanoparticles in poly(ethylene glycol) (PEG) for
2
amidation of aryl iodides. The reaction involves a hetero-
geneous process without an external chelating ligand, and
the Cu O nanoparticles can be recovered and recycled
2
without loss of activity. Aryl iodides having electron-
donating and -withdrawing groups are compatible to af-
ford the cross-coupled products in high yield.
In these reactions, first CuI undergoes reaction with KOH
to give the Cu O nanoparticles that catalyze the reaction
2
a
8
(
Equation 1). The role of the PEG is to facilitate the for-
9
SYNLETT 2009, No. 20, pp 3323–3327
Advanced online publication: 27.11.2009
DOI: 10.1055/s-0029-1218368; Art ID: D24409ST
x
x
.x
x
.2
0
0
9
mation and stabilization of the nanoparticles. The size of
Cu O nanoparticles ranges from 7–10 nm and was deter-
2
©
Georg Thieme Verlag Stuttgart · New York

3
324
S. Jammi et al.
LETTER
Table 1 N-Arylation of Benzamide with 1-Iodo-4-methylbenzenea
O
O
NH2
N
H
czpper szurce
2a
+
+
PEG, base, 120 °C
I
OH
3a
Entry PEG
Base
Cu source Time (h) Product (%)b,e
2
a
3a
Figure 2 TEM images of Cu O nanoparticles of PEG4000. Reaction
2
after (a) first cycle and (b) third cycle.
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
PEG200
PEG400
KOH
KOH
KOH
KOH
KOH
NaOH
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
12
12
12
12
20
12
12
12
12
12
12
56
62
68
79
72
60
30
36
46
24
10
PEG1500
PEG4000
PEG6000
PEG4000
PEG4000
PEG4000
PEG4000
7
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
Cs CO
2
3
Figure 3 Powder XRD pattern of Cu O nanoparticles of PEG4000.
Reaction after (a) first cycle and (b) third cycle.
2
K CO
2
3
K PO
3
4
vacuum, the Cu O nanoparticles were reused for reaction
2
1
1
1
1
1
1
PEG4000
KOH
KOH
KOH
KOH
KOH
KOH
67c
of benzamide with 1-iodo-4-methylbenzene. This process
was repeated for three runs, and the results are presented
in Table 3. The reactions proceeded well to afford the C–
N cross-coupled product in >78% yield. The TEM micro-
69d
PEG4000
Cu O
2
PEG4000
PEG4000
PEG4000
PEG4000
CuO nano 12
53
32
37
35
graph and powder X-ray diffraction analysis of the Cu O
2
CuCl2
12
12
12
nanoparticles recovered from the third run were identical
to those of the first run which clearly suggests that the
shape and size of the nanoparticles remain intact during
the recyclability (Figures 2 and 3). In addition, to study
CuSO4
Cu O
2
the leaching of the Cu O nanoparticles in PEG, CuI and
a
2
Benzamide (1.2 mmol), 1-iodo-4-methylbenzene (1 mmol), copper
KOH were stirred in PEG4000 at 120 °C for 10 hours, and
the residue was dissolved in ethyl acetate and centrifuged.
The supernatant layer was collected and ethyl acetate was
evaporated. The resulting PEG4000 residue was investigat-
ed for the cross-coupling reaction of benzamide with 1-
iodo-4-methylbenzene at 120 °C for 10 hours. However,
source (10 mol%), and base (1.5 mmol) were stirred at 120 °C in PEG
(
1 g) under nitrogen atmosphere.
Determined from 400 MHz H NMR.
b
1
c
d
e
5
5
mol% CuI used.
mol% Cu O used.
2
n.d. = not detected.
mined by transmission electron microscopy (TEM,
Figure 2) and their identities were established using the
8
b
powder X-ray diffraction analysis (Figure 3).
+
2KOH
2KI
– H2O
2CuI
2Cu(OH±
Cu2O ꢀaꢀzpartic-es
–
Equation 1
Finally, the recyclability of the Cu O nanoparticles was
2
studied. After completion of the reaction of benzamide
with 1-iodo-4-methylbenzene, the reaction material was
treated with ethyl acetate (10 mL) and water (5 mL). The
aqueous layer having the Cu O nanoparticles were centri-
2
fuged, and the precipitate was washed with deionized wa-
ter (3 × 2 mL) and acetone (3 × 2 mL). After drying under
Scheme 1 Proposed catalytic cycle
Synlett 2009, No. 20, 3323–3327 © Thieme Stuttgart · New York

LETTER
Reusable Cu O-Nanoparticles-Catalyzed Amidation of Aryl Iodides
3325
2
no reaction was observed, and the starting material was re- to give intermediate b. The latter with the nitrogen nucleo-
covered intact. These results clearly reveal that no leach- philes can give intermediate c that could complete the cat-
ing of the catalyst is involved.
alytic cycle by reductive elimination of the cross-coupled
product.
The proposed catalytic cycle for these reactions is shown
in Scheme 1. The PEG-stabilized Cu O nanoparticles a In conclusion, the synthesis and catalysis of Cu O nano-
2
2
may undergo reaction on the surface with the aryl iodide particles for amidation of aryl iodides is described in
Table 2 N-Arylation of Amides with Aryl Iodidesa
I
Cu2O ꢀaꢀz (5 mz-%±
1
2
1 2
R R NH +
R R NH
PEG4000, KOH
20 °C
R3
R3
1
R3 = OMe, Br, Me
1
2
Yield (%)b
73
Entry
1
R R NH
Aryl iodide
Time (h)
10
Product
O
O
I
O
O
NH2
N
H
I
2
17
70
NH2
N
H
OMe
OMe
Br
O
O
O
O
O
O
O
I
3
4
5
6
7
12
12
15
16
12
76
75
75
72
80
NH2
NH2
NH2
N
H
Br
I
N
H
OMe
O
O
O
I
N
H
MeO
I
NH2
NH2
N
H
I
N
H
O
I
I
I
O
8
9
3
3
5
75
70
75
NH2
O
N
H
O
NH2
N
4
4
H
O
O
10
O
NH
O
N
a Amide (1.2 mmol), aryl iodide (1 mmol), CuI (10 mol%), and KOH (1.5 mmol) were stirred at 120 °C in PEG4000 (1 g) under nitrogen atmo-
sphere.
b Isolated yield.
Synlett 2009, No. 20, 3323–3327 © Thieme Stuttgart · New York

3
326
S. Jammi et al.
LETTER
Soc. 2007, 129, 13001. (e) Yin, J.; Buchwald, S. L. Org.
a
Table 3 Recycling of the Cu O Nanoparticles
2
Lett. 2000, 2, 1101. (f) Hartwig, J. F.; Kawatsura, M.;
Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M.
J. Org. Chem. 1999, 64, 5575. (g) Ghosh, A.; Sieser, J. E.;
Riou, M.; Cai, W.; Rivera-Ruiz, L. Org. Lett. 2003, 5, 2207.
O
O
I
NH2
5 mz-% Cu2O
PEG4000, KOH
N
+
H
(
h) Manley, P. J.; Bilodeau, M. T. Org. Lett. 2004, 6, 2433.
120 °C, 12 h
(
i) Shen, Q.; Shekhar, S.; Stambuli, J. P.; Hartwig, J. F.
Angew. Chem. Int. Ed. 2005, 44, 1371. (j) Klapars, A.;
Campos, K. R.; Chen, C.-Y.; Volante, R. P. Org. Lett. 2005,
Run
Product (%)
Cu O nanoparticles recoverability (%)
1
2b
3b
7, 1185.
79
>99
78
99
78
99
(
5) For some examples, see: (a) Klapars, A.; Antilla, J. C.;
Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123,
2
7
727. (b) Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L.
a Benzamide (6 mmol), 1-iodo-4-methylbenzene (5 mmol), CuI (10
mol%), and KOH (7.5 mmol) were stirred at 120 °C in PEG4000 (5 g)
under nitrogen atmosphere.
J. Am. Chem. Soc. 2005, 127, 4120. (c) Pan, X.; Cai, Q.;
Ma, D. Org. Lett. 2004, 6, 1809. (d) Klapars, A.; Huang, X.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421.
b Recovered Cu O nanoparticles used.
2
(
e) Mallesham, B.; Rajesh, B. M.; Reddy, P. R.; Srinivas, D.;
Trehan, S. Org. Lett. 2003, 5, 963. (f) Hosseinzadeh, R.;
Tajbakhsh, M.; Mohadjerani, M.; Mehdinejad, H. Synlett
PEG4000.10 It is free from the addition of the external
chelating ligands, and the catalyst can be recycled without
loss of activity.
2
004, 1517. (g) Guo, X.; Rao, H.; Fu, H.; Jiang, Y.; Zhao, Y.
Adv. Synth. Catal. 2006, 348, 2197. (h) Lv, X.; Bao, W.
J. Org. Chem. 2007, 72, 3863.
(
6) For some examples, see: (a) Deng, W.; Wang, Y.-F.; Zou,
Y.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2004, 45, 2311.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
(
b) Chen, Y.-J.; Chen, H.-H. Org. Lett. 2006, 8, 5609.
(c) Soares do Rêgo Barros, O.; Nogueira, C. W.;
Stangherlin, E. C.; Menezes, P. H.; Zeni, G. J. Org. Chem.
006, 71, 1552. (d) Cristau, H.-J.; Cellier, P. P.; Spindler,
J.-F.; Taillefer, M. Chem. Eur. J. 2004, 10, 5607.
e) Chandrasekhar, S.; Sultana, S. S.; Yaragorla, S. R.;
Reddy, N. R. Synthesis 2006, 839. (f) Moriwaki, K.; Satoh,
K.; Takada, M.; Ishino, Y.; Ohno, T. Tetrahedron Lett. 2005,
2
Acknowledgment
(
This work was supported by Department of Science and Technolo-
gy, New Delhi, and Council of Scientific and Industrial Research,
New Delhi. We thank Centre for Nanotechnology and Central In-
strument Facility, Indian Institute of Technology Guwahati, for
TEM and XRD analysis, respectively.
46, 7559. (g) Strieter, E. R.; Bhayana, B.; Buchwald, S. L.
J. Am. Chem. Soc. 2009, 131, 78. (h) Mino, T.; Harada, Y.;
Shindo, H.; Sakamoto, M.; Fujita, T. Synlett 2008, 614.
(
i) Zhu, L.; Cheng, L.; Zhang, Y.; Xie, R.; You, J. J. Org.
References and Notes
Chem. 2007, 72, 2737.
7) For some examples, see: (a) Rout, L.; Sen, T. K.;
Punniyamurthy, T. Angew. Chem. Int. Ed. 2007, 46, 5583.
(
(
1) (a) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev.
004, 248, 2337. (b) Hartwig, J. F. Synlett 2006, 1283.
c) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003,
2
(
(
b) Rout, L.; Jammi, S.; Punniyamurthy, T. Org. Lett. 2007,
9, 3397. (c) Jammi, S.; Sakthivel, S.; Rout, L.; Mukherjee,
42, 5400. (d) Corbet, J.-P.; Mignani, G. Chem. Rev. 2006,
T.; Mandal, S.; Mitra, R.; Saha, P.; Punniyamurthy, T.
J. Org. Chem. 2009, 74, 1971. (d) Zhang, J.; Zhang, Z.;
Wang, Y.; Zheng, X.; Wang, Z. Eur. J. Org. Chem. 2008,
106, 2651. (e) Evano, G.; Blanchard, N.; Toumi, M. Chem.
Rev. 2008, 108, 3054. (f) Kondo, T.; Mitsudo, T.-A. Chem.
Rev. 2000, 100, 3205.
5
112. (e) Li, J.-H.; Tang, B.-X.; Tao, L.-M.; Xie, Y.-X.;
Liang, Y.; Zhang, M.-B. J. Org. Chem. 2006, 71, 7488.
f) Tang, B.-X.; Wang, F.; Li, J.-H.; Xie, Y.-X.; Zhang,
(
2) (a) Voets, M.; Antes, I.; Scherer, C.; Muller-Vieira, U.;
Biemel, K.; Barassin, C.; Marchais-Oberwinkler, S.;
Hartmann, R. W. J. Med. Chem. 2005, 48, 6632. (b) Quan,
M. L.; Lam, P. Y. S.; Han, Q.; Pinto, D. J. P.; He, M. Y.; Li,
R.; Ellis, C. D.; Clark, C. G.; Teleha, C. A.; Sun, J. H.;
Alexander, R. S.; Bai, S.; Luettgen, J. M.; Knabb, R. M.;
Wong, P. C.; Wexler, R. R. J. Med. Chem. 2005, 48, 1729.
(
M.-B. J. Org. Chem. 2007, 72, 6294.
(
(
8) (a) Wu, W.-T.; Wang, Y.; Shi, L.; Pang, W.; Zhu, Q.; Xu, G.;
Lu, F. J. Phys. Chem. B 2006, 110, 14702. (b) Gou, L.;
Murphy, C. J. Nano Lett. 2003, 3, 231.
9) (a) Liu, L.; Zhang, Y.; Wang, Y. J. Org. Chem. 2005, 70,
(
c) De Martino, G.; Edler, M. C.; La Regina, G.; Colsuccia,
6122. (b) Reed, N. N.; Dickerson, T. J.; Boldt, G. E.; Janda,
A.; Barbera, M. C.; Barrow, D.; Nicholson, R. I.; Chiosis,
G.; Brancale, A.; Hamel, E.; Artico, M.; Silvestri, R. J. Med.
Chem. 2006, 49, 947. (d) Kadlor, S. W.; Kalish, V. J.;
Davies, J. F.; Shetty, B. V.; Fritz, J. E.; Appelt, K.; Burgess,
J. A.; Campanale, K. M.; Chirgadze, N. Y.; Clawson, D. K.;
Dressman, B. A.; Hatch, S. D.; Khalil, D. A.; Kosa, M. B.;
Lubbehusen, P. P.; Muesing, M. A.; Patick, A. K.; Reich, S.
H.; Su, K. S.; Tatlock, J. H. J. Med. Chem. 1997, 40, 3979.
3) Goldberg, I. Ber. Dtsch. Chem. Ges. 1906, 39, 1691.
4) For some examples, see: (a) Yin, J.; Buchwald, S. L. J. Am.
Chem. Soc. 2002, 124, 6043. (b) Huang, X.; Anderson,
K. W.; Zim, D.; Jiang, L.; Klapars, A.; Buchwald, S. L.
J. Am. Chem. Soc. 2003, 125, 6653. (c) Shen, Q.; Hartwig,
J. F. J. Am. Chem. Soc. 2007, 129, 7734. (d) Ikawa, T.;
Barder, T. E.; Biscoe, M. R.; Buchwald, S. L. J. Am. Chem.
K. D. J. Org. Chem. 2005, 70, 1728. (c) Chandrasekhar, S.;
Narsihmulu, Ch.; Sultana, S. S.; Reddy, N. R. Org. Lett.
2
002, 4, 4399. (d) Svennebring, A.; Garg, N.; Nilsson, P.;
Hallberg, A.; Larhed, M. J. Org. Chem. 2005, 70, 4720.
e) Wang, L.; Zhang, Y.; Liu, L.; Wang, Y. J. Org. Chem.
006, 71, 1284.
(
2
(
10) General Procedure for Amidation of Aryl Iodides
Aryl iodide (1 mmol), amide (1.2 mmol), and CuI (10 mol%)
were stirred at 120 °C in the presence of KOH (1 mmol) in
(
(
PEG4000 (1 g) under N atmosphere. Progress of the reaction
2
was monitored by TLC. After completion, the reaction flask
was cooled to r.t., and the reaction mixture was treated with
EtOAc (10 mL). The resulting solution was washed with
H O (3 × 2 mL). Drying (Na SO ) and evaporation of the
2
2
4
Synlett 2009, No. 20, 3323–3327 © Thieme Stuttgart · New York

LETTER
Reusable Cu O-Nanoparticles-Catalyzed Amidation of Aryl Iodides
3327
2
solvent gave a residue that was purified on a short pad of
silica gel using hexane and EtOAc as eluent. All the isolated
products were characterized by IR, H NMR, and C NMR
spectroscopy, and elemental analysis.
After the reaction, the reaction material was treated with
EtOAc (10 mL) and H O (5 mL). The aqueous layer having
2
1
13
the Cu O nanoparticles were centrifuged, and the precipitate
2
was washed with deionized H O (3 × 2 mL) and acetone
2
Recyclability Experiment
(3 × 2 mL). After drying in vacuum, the Cu O nanoparticles
2
1-Iodo-4-methylbenzene (5 mmol), benzamide (6 mmol),
were reused for the fresh reaction of benzamide with 1-iodo-
4-methylbenzene.
and CuI (10 mol%) were stirred at 120 °C in the presence of
KOH (7.5 mmol) in PEG4000 (5 g) under N atmosphere.
2
Synlett 2009, No. 20, 3323–3327 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.