Copper(II) trans-bis-(glycinato): An efficient heterogeneous catalyst for cross coupling of phenols with aryl halides

Article abstract of DOI:10.1016/j.tetlet.2012.06.071

Copper(II) trans-bis-(glycinato) complex, easily prepared by the solid state reaction of copper(II) acetate and glycine (trans-[Cu(glyo) ₂·H₂O]) was found to be an efficient, recyclable, and high yielding catalyst for the Ullmann type synthesis of diaryl ethers via the cross coupling of phenols with aryl halides without using any additives at relatively low reaction temperature. The catalyst could easily be recovered by simple filtration and was reused for several runs with consistent catalytic activity.

Full text of DOI:10.1016/j.tetlet.2012.06.071

Tetrahedron Letters 53 (2012) 4665–4668
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Tetrahedron Letters
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Copper(II) trans-bis-(glycinato): an efficient heterogeneous catalyst for
cross coupling of phenols with aryl halides
⇑
Sanny Verma, Neeraj Kumar, Suman L. Jain
Chemical Sciences Division, CSIR–Indian Institute of Petroleum, Mohkampur, Dehradun 248005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Copper(II) trans-bis-(glycinato) complex, easily prepared by the solid state reaction of copper(II) acetate
and glycine (trans-[Cu(glyo)2ÁH2O]) was found to be an efficient, recyclable, and high yielding catalyst for
the Ullmann type synthesis of diaryl ethers via the cross coupling of phenols with aryl halides without
using any additives at relatively low reaction temperature. The catalyst could easily be recovered by sim-
ple filtration and was reused for several runs with consistent catalytic activity.
Received 30 March 2012
Revised 12 June 2012
Accepted 15 June 2012
Available online 19 June 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Ullmann coupling
Diaryl ether
Copper
Glycine
Phenol
Diaryl ethers are valuable structural motifs which are widely
used in the synthesis of numerous synthetically challenging and
biologically active molecules.1 Conventionally, these compounds
are prepared by intermolecular reaction between aryl halide and
phenol using copper or palladium as catalyst.2,3 However, harsh
reaction conditions, use of stoichiometric quantities of the copper
catalyst, and the low yields have significantly limited the effective-
ness of this reaction. Therefore, improved coupling methodologies
using catalytic amounts of a copper precursor in the presence of
various ligands such as 1,10-phenanthroline,4 2,2,6,6-tetramethyl-
heptane-3,5-dione,5 triphenylphosphine,6 phosphazene,7a ethylene
glycol,7b neocuproine,8 N-methyl glycine,7c,d oxime-phosphine
oxide ligand,7e a tripod ligand,7f benzotriazole,7g 1,2-diaminocyclo-
ligands/additives, and are economically less affordable, there is a
need to develop a convenient and cost effective catalyst system.
In continuation of our interest toward developing new methodolo-
gies for coupling reactions, herein we report an efficient, cheap,
easily accessible, and reusable heterogeneous catalyst copper(II)
trans -bis-(glycinato) 1 for the Ullmann type synthesis of diaryl
ethers via cross coupling of phenols with aryl halides without
any additive at relatively low reaction temperature (Scheme 1).
The required catalyst was easily synthesized via the grinding of
Cu(CH3COO)2ÁH2O and glycine in a 1:2 molar ratio as following the
literature procedure.12,13 The values of elemental analyses sug-
gested the proposed formula of complex is trans-[Cu(gly)2(H2O)]
1. Further, a strong band at 1699 cmÀ1 in IR spectra corresponding
to carboxyl group of glycine revealed the successful formation of
adduct 1. The stability of the complex was determined by the ther-
mo gravimetric analysis (TGA) under oxygen atmosphere. The TG
curve of the complex 1 showed two-step decomposition pattern
(Supplementary Fig. 1). In the first stage, weight loss was observed
in the temperature range of 50–150 °C, which is probably due to
the loss of coordinated water molecule. The second stage
hexane,7h -proline,7i 8-hydroxyquinoline,9 (2-pyridyl)acetone,10
L
and 1-naphthoic acid2a under relatively mild reaction conditions
are receiving increasing interest in recent years. However, the
use of expensive, less conveniently available reagents or additives
and homogeneous protocols is the major drawback associated with
most of the existing methods. In the recent years, the utilization of
heterogeneous catalysts in organic synthesis has been increased
due to their facile recovery and recycling ability of the catalysts.
In this context, various heterogeneous copper catalysts including
nanoparticulate CuO,11a nano CuI,3a,b Cu2O,4 and Cu nanoparti-
cles11b have been used for Ullmann type coupling. Since the
reported catalysts are difficult to synthesize, require excess
OH
O
1 (2 mol %)
X
R
R
KOH (2.0 equiv.)
DMSO (2 ml), 80oC, 8 h
X=I, Br
R = H, phenyl
⇑
Corresponding author.
E-mail addresses: sumanjain@hotmail.com, suman@iip.res.in (S.L. Jain).
Scheme 1. Copper-catalyzed Ullmann coupling.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.071

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S. Verma et al. / Tetrahedron Letters 53 (2012) 4665–4668
decomposition was taken place in the temperature range between
250 and 500 °C with the final formation of CuO.
gand during the reaction; (ii) catalyst is heterogeneous which
can easily be recovered by simple filtration; (iii) simple work-up
and offers high product yield. Furthermore, the reaction of phenol
with chlorobenzene did not give any coupling product under de-
scribed experimental conditions. We compared the potential of
the developed catalyst with some of the already reported copper
catalysts for the coupling of phenols with aryl halides. These re-
sults are presented in Table 1 (entries 2 and 5). The higher product
yield in comparatively lesser reaction times in the absence of addi-
tional additive clearly indicates the superiority of the developed
methodology.
Next, we tested the recycling of the developed catalyst by
choosing the coupling of phenol with iodobenzene under described
experimental conditions. After completion of the reaction, the cat-
alyst could easily be recovered by simple filtration and used for the
subsequent experiments (7 runs). The results of these experiments
are summarized in Table 3. As shown, the yield of the product and
reaction time remained almost same in all cases, establishing the
efficient recycling of the catalyst as well as heterogeneous nature
of the developed methodology. Further we also analyzed the recov-
ered catalyst by Inductive Coupled Plasma-Atomic Emission Spec-
troscopy (ICP-AES) analysis and the value of copper was found to
be same as in fresh catalyst, ascertaining that the reaction is truly
heterogeneous in nature.
At first, we studied the coupling of phenol with various aryl ha-
lides mediated with KOH in the presence of catalytic amount of 1
(2 mol %) at 80 °C in dimethyl sulfoxide without using any addi-
tive.14 The results of these experiments are summarized in Table
1. As shown in the results, both aryl iodides and bromides were
found to be efficient and provided moderate to high yield of the
product. However, the steric hindrance of aryl halides such as 2-
iodoanisole was found to disfavor this reaction and provided com-
paratively lower yield of the desired product (Table 1, entry 3). It
was found that the reaction did occur promisingly at 80 °C in
dimethyl sulfoxide in comparison to the other solvents such as ace-
tonitrile, THF, and dichloroethane under similar reaction condi-
tions (Table 1, entry 1). Next, we carried out the Ullmann
coupling of different phenols/naphthols with phenyl iodide/ bro-
mide with the use of 1 (2 mol %) in the presence of KOH in DMSO
under similar reaction conditions. The results are summarized in
Table 2. As shown, all the substrates were found to be effective
and afforded moderate to high yields of the corresponding diaryl
ethers. In all cases, the products were confirmed by GC/MS analysis
and their identity was established by comparing their spectral data
with those of reported compounds. Among the various phenols,
those substituted with electron donating groups were found to
be more reactive substrates as compared to those having electron
withdrawing groups (Table 2, entries 13–18). The sterically hin-
dered phenols such as 2-methoxyphenol, 2,4-dimethoxyphenol
also provided moderate yield of the product under the described
reaction conditions (Table 2, entries 5,9,10–11). The use of 1-naph-
thol and 2-naphthol in place of phenol also provided comparable
results under the described reaction conditions (Table 2, entries
19 and 20). The developed protocol is advantageous over the re-
ported method7c,d in many ways; (i) it does not require excess li-
In summary, we have developed an efficient, cost-effective, eas-
ily accessible, and recyclable catalyst for carrying out the Ullmann
diaryl ether synthesis without using any additive under mild reac-
tion conditions. The key advantages of the developed method are:
(i) facile synthesis of the catalyst, (ii) low reaction temperature (iii)
tolerance to various functional groups, (iv) facile recovery, and
recycling of the catalyst. Further applications of the developed cat-
alyst as well as mechanistic studies, are currently in progress in our
laboratory.
Table 1
Ullmann coupling of phenol with different aryl/alkyl halidesa
R1
O
1 (2 mol %)
KOH (2.0 equiv.)
DMSO (2 ml), 80oC, 8 h
I
OH
R1
X = I, Br
R1= OMe
Entry
1
Aryl/alkyl halide
Product
Solvent
Time (h)
Yieldb (%)
98a
65c
O
O
DMSO
CH3CN, THF,
ClCH2CH2Cl
8
12
24
24
I
40d
40e
2
3
DMSO
18
84f
I
OMe
I
OMe
O
DMSO
DMSO
12
44
98a
95g
O
8
8
MeO
I
4
5
MeO
88a
88f
O
DMSO
8
18f
Br
a
b
c
d
e
f
Reaction conditions: phenol (2 mmol), aryl/alkyl halide (2 mmol), KOH (2 equiv), catalyst (2 mol %), DMSO (5 ml) at 80 °C.
Isolated yields.
Using CH3CN.
THF.
Dichloroethane.
Ref. 2c.
g
Ref. 10.

S. Verma et al. / Tetrahedron Letters 53 (2012) 4665–4668
4667
Table 2
Heterogeneous copper-catalyzed Ullmann coupling of phenols/naphtholsa
OH
O
1 (2 mol %)
X
R
R
KOH (2.0 equiv.)
DMSO (2 ml), 80oC, 8 h
X=I, Br
R = H, phenyl
Entry
1
Substrate
Aryl halide
Product
Yieldb (%)
O
X
X
H2N
OH
OH
98 (X = I)
95 (X = Br)
H2N
H2N
H2N
O
95 (X = I)
93 (X = Br)
2
3
4
OH
OH
O
X
X
X
MeO
MeO
90 (X = I)
87 (X = Br)
MeO
MeO
O
92 (X = I)
85 (X = Br)
OMe
OH
OMe
OMe
O
92 (X = I)
85 (X = Br)
5
OMe
O
X
X
X
X
H3C
H3C
OH
OH
98 (X = I)
96 (X = Br)
6
7
8
H3C
H3C
O
86 (X = I)
82 (X = Br)
OH
H3C
H3C
O
97 (X = I)
94 (X = Br)
H3C
H3C
CH3
CH3
OH
O
82 (X = I)
76 (X = Br)
9
CH3
CH3
CH3
CH3
CH3
X
O
OH
90 (X = I)
86 (X = Br)
10
11
H3C
H3C
CH3
OH
CH3
X
O
92 (X = I)
88 (X = Br)
H3C
H3C
CH3
CH3
H3C
H3C
X
O
H3C
94 (X = I)
90 (X = Br)
OH
12
H3C
H3C
CH3
CH3
O
CH3
H3C
O2N
X
X
OH
55 (X = I)
48 (X = Br)
13
14
15
O2N
NO2
NO2
OH
62 (X = I)
50 (X = Br)
O
H3C
Cl
H3C
Cl
O
X
84 (X = I)
80 (X = Br)
OH
(continued on next page)

4668
S. Verma et al. / Tetrahedron Letters 53 (2012) 4665–4668
Table 2 (continued)
Entry
Substrate
Aryl halide
Product
Yieldb (%)
Cl
Cl
X
80 (X = I)
74 (X = Br)
O
16
17
OH
Cl
Cl
X
O
70 (X = I)
66 (X = Br)
H2N
Br
OH
H2N
Br
Cl
Cl
O
X
X
OH
62 (X = I)
55 (X = Br)
18
19
OH
O
90 (X = I)
80 (X = Br)
OH
O
89 (X = I)
X
20
82 (X = Br)
a
Reaction conditions as mentioned in the text.
Isolated yields.
b
2006, 128, 2180; (d) Fernandez Rodriguez, M. A.; Shen, Q.; Hartwig, J. F. Chem.
Eur. J. 2006, 12, 7782.
Table 3
Results of recycling experiments
4. (a) Hosseinzadeh, R.; Tajbakhsh, M.; Mohadjerani, M.; Alikarami, M. Synlett
2005, 1101; (b) Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Org. Lett. 2001, 3,
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5. Buck, E.; Song, Z. J.; Tschaen, D.; Dormer, P. G.; Volante, R. P.; Reider, P. J. Org.
Lett. 2002, 4, 1623.
O
1 (2 mol %)
I
OH
KOH (2.0 equiv.)
DMSO (2 ml), 80oC, 8 h
Run
1
2
3
4
5
6
7
6. Gujadhur, R. K.; Venkataraman, D. Synth. Commun. 2001, 31, 2865.
7. (a) Palomo, C.; Oiarbide, M.; Lopez, R.; Gomez-Bengoa, E. Tetrahedron Lett. 2000,
41, 1283; (b) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2002, 4, 3517; (c) Deng, W.;
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Org. Lett. 2003, 5, 3799; (e) Zhu, D.; Xu, L.; Wu, F.; Wan, B. Tetrahedron Lett.
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9. (a) Fagan, P. J.; Hauptman, E.; Shapiro, R.; Casalnuovo, A. J. Am. Chem. Soc. 2000,
122, 5043; (b) Corbet, J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651.
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Yield
98
98
97
98
97
97
97
Acknowledgment
We are thankful to the Director, IIP for his kind permission to
publish these results. S.V. acknowledges CSIR, New Delhi for the
award of his Research Fellowship. Analytical division of the Insti-
tute is kindly acknowledged for providing the analysis (GC–MS,
IR &1H NMR) of the products.
12. (a) Jia, D. Z.; Xin, X. Q. Acta Chim. Sinica 1993, 51, 358; (b) Wang, L.; Lang, L.;
Dianzeng, J.; Yali, C.; Xinquan, X. Chin. Sci. Bull. 2005, 50, 758.
Supplementary data
13. Synthesis of copper(II) trans-bis-(glycinato) complex12: Reagent grade copper(II)
acetate monohydrate {Cu(OCOCH3)2ÁH2O} and glycine were used. Copper
acetate monohydrate and glycine were taken in a 1:2 molar ratio and ground
for 5–10 min in an agate mortar respectively for mixing. The mixture was
ground for 60 min and the reaction was checked by infrared spectrum as it
showed the reduction of the free amino band of the glycine. At the end of the
reaction (absence of free amino band in IR spectrum), the synthesized complex
was washed twice with ethanol and dried. Anal. Calcd for C4H10N2O5Cu (%): C,
20.91; H, 4.39; N, 12.20%. Found: C 20.78, H 4.46, N 12.86%.
14. Experimental procedure for the synthesis of diaryl ether: To a stirred solution of
iodo benzene (1.0 mmol) and phenol (1.0 mmol) in dry DMSO (2.0 ml) were
added Cu catalyst 1 (0.02 mmol) and KOH (2.0 equiv) and the reaction mixture
was heated at 80 °C for 8 h. The progress of the reaction was monitored by TLC.
After being cooled the reaction mixture at room temperature, the precipitated
catalyst was separated by simple filtration and filtrate so obtained was diluted
with ethyl acetate (10 ml). The organic layer was washed with water and dried
over anhydrous Na2SO4. The solvent was evaporated under vacuum to give the
crude product, which was purified by column chromatography with hexane as
eluent to yield the expected product as yellowish oil. The products were
analyzed by GC–MS, IR, 1H & 13C NMR analysis.
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.
2012.06.071.
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