Cu–Fe layered double hydroxide derived mixed metal oxide: Environmentally benign catalyst for Ullmann coupling of aryl halides

Article abstract of DOI:10.1016/j.poly.2016.09.052

Solid mixed metal oxide derived from Cu–Fe-layered double hydroxide by its thermal decomposition at 600?°C has been demonstrated as novel ligand free catalyst for the synthesis of biphenyls through C–C coupling. The catalytic efficiency of this material has been studied by varying the solvents and bases, thereby their influence in controlling the product formation. The C–C coupling yield of aryl halides were found to be higher, when dimethylformamide and potassium carbonate used as a solvent and base respectively. The catalyst can be easily separated from the reaction mixture, simply by filtration and reused several times without significant loss of its activity. The mixed metal oxide has been characterized by XPS, XRD, SEM, BET, TG analysis and the role of calcined Cu–Fe layered double hydroxide in catalyzing C–C coupling reaction was proposed. Moreover, it is ligand-free C–C coupling reaction and is promising alternative than the conventional homogeneous and heterogeneous Pd catalysts.

Full text of DOI:10.1016/j.poly.2016.09.052

Accepted Manuscript
Cu-Fe layered double hydroxide derived mixed metal oxide: Environmentally
benign catalyst for Ullmann coupling of aryl halides
Deepa Dumbre, Vasant R. Choudhary, PR. Selvakannan
PII:
S0277-5387(16)30482-X
http://dx.doi.org/10.1016/j.poly.2016.09.052
POLY 12240
DOI:
Reference:
Polyhedron
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Revised Date:
Accepted Date:
31 May 2016
24 September 2016
27 September 2016
Please cite this article as: D. Dumbre, V.R. Choudhary, PR. Selvakannan, Cu-Fe layered double hydroxide derived
mixed metal oxide: Environmentally benign catalyst for Ullmann coupling of aryl halides, Polyhedron (2016), doi:
http://dx.doi.org/10.1016/j.poly.2016.09.052
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Cu-Fe layered double hydroxide derived mixed metal oxide:
Environmentally benign catalyst for Ullmann coupling of aryl halides
Deepa Dumbre, Vasant R Choudhary*, PR. Selvakannan*
Centre for Advanced Materials and Industrial Chemistry, School of Applied Sciences, RMIT
University, Melbourne – 3000 (Australia)
Abstract
Solid mixed metal oxide derived from Cu-Fe-layered double hydroxide by its thermal
decomposition at 600 oC has been demonstrated as novel ligand free catalyst for the synthesis
of biphenyls through C-C coupling. The catalytic efficiency of this material has been studied
by varying the solvents and bases, thereby their influence in controlling the product
formation. The C-C coupling yield of aryl halides were found to be higher, when
dimethylformamide and potassium carbonate used as a solvent and base respectively. The
catalyst can be easily separated from the reaction mixture, simply by filtration and reused
several times without significant loss of its activity. The mixed metal oxide has been
characterized by XPS, XRD, SEM, BET, TG analysis and the role of calcined Cu-Fe layered
double hydroxide in catalyzing C-C coupling reaction was proposed. Moreover, it is ligand-
free C-C coupling reaction and is promising alternative than the conventional homogeneous
and heterogeneous Pd catalysts.
Keywords: Cu-Fe-hydrotalcite; Heterogeneous Catalysis; Ullmann coupling, Biaryls
__________________________________________________________________________________
Corresponding authors:
Dr. PR. Selvakannan ; Dr Vasant R Choudhary
Center for Advanced Materials and Industrial Chemistry
School of Applied Sciences, RMIT University,
Melbourne, Australia 3000
Phone Number +61(3) 9925 0805
Mobile Number: +61(3) 450862711
Email: selvakannan.periasamy@rmit.edu.au : vrc0001@yahoo.com
1

1. Introduction
The Ullmann condensation reaction has long been studied by chemists for C-C bond
formation between two phenyl or substituted phenyl rings to form biaryls because biaryls
play an important role in modern synthetic organic chemistry [1]. This coupling reaction
between two aryl halide molecules leads to the elimination of two halide groups that result in
the formation of the C-C bond towards the synthesis of biaryls. This reaction is usually
carried out by converting two moles of aryl halide into a biaryl in the presence of finely
granulated metallic copper at temperatures above 170 ºC, wherein halides are eliminated as
copper halides. Metallic copper has been demonstrated as an effective reagent for this type of
condensation reaction. There have been many reports in the literature about the conventional
Ullmann coupling [2 - 4] and the use of stoichiometric amounts of copper, nickel, zinc and
palladium as a reagent/catalyst has been comprehensively reviewed [5] due to the
significance of biaryls as building blocks for the synthesis of polyketides, terpenes,
coumarins, flavonoids, tannins, and alkaloids.
As mentioned earlier, this reaction have the disadvantages that includes high
temperature, elimination of copper halides, poor product yields and sensitive to reaction
conditions. Therefore, various attempts have been made and reported in the literature to
improve the product yield with ambient reaction conditions. In some cases, the reaction rate
can be accelerated by carrying out the reaction under the influence of ultrasound [6]. In
addition to copper, there are other metals like Nickel, Zinc and palladium were also used for
Ullmann coupling. Nickel catalysts have been used to promote C-C coupling [7] to produce
natural products and palladium based catalysts were also used to catalyze the couplings in
presence of trialkylamine base [8]. Homocoupling of aryl halide by palladium acetate and
tetra-n-butylammonium bromide mixture [9] have been reported for the synthesis of various
substituted biphenyls. In a recent work, it has been demonstrated that [10] catalytic amount of
2

palladium and zinc mediated reductive coupling of aryl halides at ambient temperature and
air in water. Ullmann type coupling were recently carried out under solvent less conditions
using stoichiometric amounts of Palladium and zinc in presence of water and liquid carbon
dioxide [11] and fluorinated palladium catalyzed coupling reaction in supercritical carbon
dioxide [12]. Commercially available zinc dust was also demonstrated as an active catalyst
for the synthesis of symmetrical functionalized biaryls from aryl halides using ammonium
formate as base [13]. One-pot synthesis of symmetrical biaryls [14] for the synthesis of
biologically active secalonic acid, has also been reported. Zinc and carbon supported Pd
catalyzed Ullmann homocouplings under sonochemical conditions in aqueous media under
CO2 bubbling have also been demonstrated without using any donor solvents [15]. Very
recently, a few catalysts have also been reported using N-heterocyclic carbene (NHC)
polymer [16], CuNPs/nanoporous polymer [17], Cu-TDPAT [18] for various Ullmann
coupling reactions.
Most of the afore-mentioned methods, either expensive metals like palladium were
used as homogeneous catalyst or transition metals like copper, nickel and zinc were used in
stoichiometric or excess amounts, which lead to the loss of metals as metal halides. Therefore
it is essential to develop a heterogeneous catalyst that contains these metals as active sites,
which can catalyze the reaction as well as significant reduction of metal leaching.
Hydrotalcites and layered double hydroxides containing these metal ions are the desired
candidates for this kind of reaction. However these materials have layered structure and have
intercalated hydroxide and carbonate ions commonly, which limits their activity towards
these C-C coupling reactions. Thermal treatment of these materials lead to the loss of these
ions and resulted in the formation of mixed metal oxides and they can be promising
candidates for these kinds of condensation reactions. Moreover, catalyst separation is easier
after the reaction completion, thereby the potential of its recycling makes these materials as
3

an important alternative to homogeneous catalysts. In the present work, we have
demonstrated a greener process for the Ullmann-type aryl–aryl coupling of aryl iodides or
bromides, forming biaryls with excellent yields at low temperature (120 ºC) using easily
separable and reusable thermally activated Cu-Fe-hydrotalcite. Presented below are the
details.
2. Experimental
2.1 Catalyst preparation and characterization
The precursor of the catalyst is the layered double hydroxide of Cu2+ and Fe3+ ions
was synthesized by co-precipitating these ions together with the addition of base and this
method adopted with few modifications from the procedure that we reported earlier [20-23].
To the aqueous solution containing the mixture of 3 mmol of copper nitrate and (3 mmol) and
ferric citrate (1 mmol), aqueous solution containing the mixture of ammonium hydroxide and
ammonium carbonate mixture were added drop-wise to increase the pH slowly. The
precipitated layered double hydroxide of copper and iron (Cu-Fe-LDH, referred hereafter),
washed several times with water to remove any free ions and dried at room temperature.
After complete drying, this material was calcined at 600 ºC for four hours under static air.
This material was used as a catalyst without any further processing and termed as CuFe-
MMO hereafter. N2 physi-sorption analysis of these materials showed that this material has
the BET surface area of 130 m2/g with the pore volume of 0.5 cm3/g.
Thermo gravimetric data (TGA) of the Cu-Fe LDH were collected using a Perkin
Elmer TGA-7 from 35 ºC to 700 ºC with a heating rate of 10 ºC per minute under the flow of
nitrogen. XRD measurements were carried out on a Bruker D8 X-ray diffraction system
operating at a voltage of 40 kV and current of 40 mA with CuKa radiation and equipped with
the Antonn Parr Heating accessory. XPS data of CuFe MMO was collected using a Thermo
9
K-5 Alpha XPS instrument at a pressure better than 1× 10− torr with core levels aligned
4

with C 1s binding energy of 284.6 eV. SEM/EDX studies of these materials were carried out
using FEI nova nano SEM, operated at 30 KV.
2.2 Catalyst activity
In a typical reaction, 5 ml of DMF was added with 2.5 mmol of aryl halide (with or
without 2.5 mmol of second aryl halide), catalyst (10 wt % in regard to aryl halide) and
3mmol of base. The mixture was stirred at 120 ºC under nitrogen atmosphere for an
appropriate time and the reaction was monitored by TLC. After completion of reaction, the
catalyst was separated by filtration and washed with DMF (3 x 3 ml). Then the filtrate was
diluted with water followed by extraction with ethyl acetate to give the crude product, which
was subsequently purified by column chromatography on silica gel with petroleum
ether/ethyl acetate as an eluent. The catalyst was further washed with acetone, dried and
reused. The reaction products were isolated by column chromatography and were confirmed
by NMR, IR, MS and elemental analysis.
3. Results and Discussion
Under the optimized conditions (presented later), the coupling reaction of aryl halides
were investigated to know the scope of our method, in DMF with K2CO3 as a base at 120 0C
to obtain coupling products in good to excellent yields (Scheme 1). The results are presented
in Table 1.
3.1 Effect of nature of aryl halide:
Results showing a strong influence of the nature of aryl halide on the biphenyl yield
in the coupling reaction are presented in Table 1. For the different halobenzenes, the biphenyl
yield was in the following order: iodobenzene > bromobenzene >> chlorobenzene >>>
flurobenzene (Table 1, entries 1-5). In the case of fluorobenzene, there was no biphenyl
formation even for a longer reaction time (Table 1, entry 5). The electronegativity of the
halogen controls the strength of C-X bond, thereby highly electronegative chlorides and
5

fluorides didn’t show much conversion into biaryls. In the absence of any catalyst the product
yield was found to be negligibly small. Previous studies were shown that reaction
temperature, bases and solvents play a key role in controlling C-C conversion, therefore this
reaction was carried out under different reaction temperature, various bases and solvents to
optimize the product yield. The obtained results showed strong influence of reaction
temperature and various bases and solvents on the product (biphenyl) yield in the coupling
reaction over the Cu-Fe-hydrotalcite catalyst (calcined at 600 oC) are given in Table 2 and 3
respectively.
3.2 Influence of the reaction temperature
To identify the optimum reaction temperature, the reaction between 4-iodoanisole
o
o
over the catalyst was carried out at different temperatures (50 C – 120 C). As expected the
product yield increased with increasing the reaction temperature; show a strong influence of
o
temperature on the reaction. The catalyst showed its activity above 50 C and the product
o
yield increased exponentially with increasing the bath temperature from 50 C to 120 oC.
3.3 Influence of the various base
In order to optimize the reaction conditions, the reaction between 4-iodoanisole over
the catalyst was carried out using different bases such as Na2CO3, NaOAC, trimethyl amine,
pyridine and zinc dust. The results in Table 2 showed a strong influence of base on coupling
of aryl halides, K2CO3 was found to be the best base for this reaction. When K2CO3 was
replaced by Na2CO3, sodium acetate, trimethyl amine and pyridine or zinc dust in the
coupling reaction, the product yield was much smaller, even for higher reaction time, than
that achieved with K2CO3. This revealed that, among the bases, K2CO3 is the most suitable
base for the CuFe MMO catalyzed Ullmann coupling. In the absence of base, the formation
of biphenyl in the coupling reaction is quite small. Thus, the coupling reaction is strongly
influenced by the base concentration.
6

3.4 Influence of the various solvents
To check the efficiency of the catalyst and to optimize the reaction conditions,
different solvents have been used in the Ullmann coupling of p-iodoanisole, under similar
reaction conditions. Even though other polar solvents like NMP, ethanol and water can be
used, but DMF showed best results with more or less active aryl halides (Table 3). The other
solvents like CH3CN and xylene gave lower yield and required longer reaction time.
However, no reaction was observed with solvents like water, 1,4-dioxan, toluene and ethanol.
Among the different solvents, DMF was found to be the best solvent most probably due to
increased competitive adsorption on the catalyst surface of the solvents for providing very
good conversion in the reaction.
The reusability of the Cu-Fe-hydrotalcite was thoroughly investigated. The catalyst
showed excellent reusability in the reaction without a significant loss in its activity in five
reuses; the biphenyl yield in the five reuses was 78 ± 2%. The catalyst (after the reaction)
was removed from the reaction mixture by filtration, washed with DMF first and then with
acetone, dried and then reused in the coupling reaction at 120 °C. This was repeated several
times. The results showing the reusability of the catalyst are presented in Table 1 (entry 6).
Since, all the products (Table 1) of the reaction are known/reported earlier; we have provided
spectral data only for a few representative products.
Spectral data
4, 4’-Dimethoxy biphenyl
1H NMR (CDCl3+CCl4, 50 MHz): δ 7.47 (d, 4H, J=8 Hz), 6.95 (d, 4H, J=8 Hz), 3.85 (s, 6H).
IR (chloroform): 3019, 2957, 1608, 1500, 1215, 1182, 1041, 824 cm-1; GC Mass: m/z 214
Biphenyl
1H NMR (CDCl3, 50 MHz): δ 7.47 (m, 6H), 7.61 (d, 4H, J = 6 Hz); IR (Neat): 3060, 1638,
1456, 1210, 898, 698, 728 cm-1.
7

3.4 Catalyst characterization
In the previous section, it was shown that thermally activated CuFe-MMO was found
to be an active catalyst as compared to its precursor Cu-Fe LDH. In order to study the
influence of thermal activation and its role in forming the mixed metal oxide phase
formation, XRD patterns of CuFe LDH material was collected as a function of temperature.
Figure 1 shows the XRD profile of the CuFe LDH at room temperature and when it was
o
heated up at higher temperatures until 600 C. Hydrolysis of Cu(II)/Fe(III) ions under basic
conditions resulted in the formation of layered double hydroxides, wherein ions like
hydroxide and carbonate intercalated between the layers. The CuFe LDH exhibit a broader
and intense X-ray reflections at 2θ 11.4 was the characteristic diffraction peak for the layered
structure and this peak shifted to higher 2θ values and disappeared completely when CuFe
o
LDH was heated above 400 C. This was an indication of layered structure of CuFe LDH
initially decreased the interplanar distance and later transformed into new crystalline phase
o
that corresponds to the mixed metal oxide. At 400 C, a new broad diffraction observed at
38.6, which corresponds to the (111) CuO phase and no peaks correspond to iron oxide was
observed. This is a general phenomenon, when hydrotalcite and layered double hydroxide
materials were calcined, the crystalline phase contain predominantly the oxide phase of the
divalent metal ion, while the trivalent metal ion gets incorporated in the framework of the
divalent metal oxide. There are few other small diffraction peaks observed, which correspond
to the CuFe2O4, mixed metal oxide phase. In order to investigate the textural properties of
these particles during calcination, SEM imaging of CuFe LDH and CuFe MMO has been
done and the images are shown in Figure 2. CuFe HT exhibit many irregular shaped particles
but each of these particles tend to have layered structure that was shown as inset in Figure
2B. After calcination, the size of the particles tends to decrease, even though are few larger
aggregates were present and may be formed as a result of calcination induced sintering of
8

particles. Energy Dispersive X-Ray (EDX) analysis of these materials clearly showed the
presence of Cu and Fe, even though there was no diffraction peaks corresponds to iron oxide.
To investigate the thermal degradation of the CuFe LDH during the calcination, thermo
gravimetric analysis of these materials were carried out and the results are presented in Figure
3. In general, LDH kind of materials tend to rehydrate it and partly restore their layered
structure, therefore TG analysis of the calcined material was also carried out and the results
are given in the Figure 3. Interestingly CuFe LDH exhibits its major sharp weight loss
o
between 300 oC – 380 C and after 400 oC there was no significant weight loss. This result is
in agreement with the XRD results, where the phase transformation of LDH to mixed metal
o
oxide was observed at 400 C. However, CuFe-MMO showed continuous weight loss due to
the loss of adsorbed water and hydrated ions like hydroxide and carbonate. This shows that
this material tend to rehydrate after calcination. This gives an important insight why this
material don’t require any ligand during the Ullmann coupling because DMF as a donor
solvent tend to rehydrate the CuFe MMO and act as weak ligand to bind with the metal site.
The surface chemistry of the CuFe-MMO needs to be studied to understand the
catalytic role of this material towards Ullmann coupling. Figure 4 shows the XPS analysis of
CuFe MMO, wherein Cu2p, O1s and Fe2p core level spectra were presented. The binding
energy of Cu2p3/2 level was observed at 934.4 eV, corresponds to the Cu2p binding energy in
the CuO phase. However, the increase in the Cu2p binding energy as compared to standard
Cu 2p binding energy in CuO may be probably due to its interaction with iron ions in the
framework. In the case of iron, the binding energy of the Fe 2p3/2 core level in the CuFe
MMO material (Fig. 4C inset) material appeared at 712 eV, slightly higher than the binding
energy value observed for iron oxy hydroxides and iron oxide. Another interesting
observation, the presence of iron was found to be lower than the iron content observed in the
EDX analysis. This was probably due to the presence of iron in the bulk CuO framework and
9

the resultant electronic interaction may be responsible for the shift in binding energy.
Analysis of O1s core level binding energies appeared in the case of CuFe MMO material
(Fig. 4B) showed two chemically distinct oxygen species. The binding energy values of the
O1s levels observed at 530.3, 531.9 were assigned to metal oxide and surface bound hydroxyl
groups. Based on this analysis, calcination of CuFe LDH led to the formation of crystalline
CuO, wherein iron oxide is incorporated. The role of copper in Ullmann coupling reaction
was mainly its oxidative addition reaction with the aryl halides and subsequent reductive
elimination of copper halides. Thermally activated CuFe MMO consists of CuO phase doped
with Fe3+ ions, which was derived from its layered precursor CuFe LDH, The addition of
base K2CO3 during the reaction partially regenerates the layered structure and enable the
copper active sites. This material has high surface area and tends to get rehydrated with the
presence of DMF. Since DMF is a donor solvent and its ability to bind with these copper site
that eventually led copper to undergo oxidative addition with aryl halides and release of
halide ions. The electronic interaction between the Copper and iron in the oxide framework
promote the halide adsorption on these sites and enable the Ullmann condensation reaction.
4. Conclusions
In conclusion, we have developed a novel ligand-free, highly efficient and
environmentally more benign method for the synthesis of biphenyls with high yields under
mild conditions, using a novel solid mixed metal oxide catalyst derived from Cu-Fe-
o
hydrotalcite (by its thermal decomposition at 600 C). In the coupling reactions of different
halo benzenes, high biphenyl product yields were achieved for iodobenzenes and
bromobenzenes but for chlorobenzenes and flurobenzenes poor product yields were obtained.
We have investigated the role of various solvents and bases in controlling the product yield
and reaction rate. It was observed that DMF and K2CO3 when they were used as solvent and
base respectively, the Ullmann condensation product was increased significantly. The CuFe
10

MMO catalyst showed high activity/selectivity and excellent reusability in the reaction.
Moreover, this catalyst is inexpensive and requires mild base like K2CO3. It can also be easily
separated from the reaction mixture and reused for the reaction without significant loss of its
activity. All these facts make this catalyst a highly promising alternative to the palladium
based homogenous or other heterogeneous solid catalysts. The high catalytic activity seems
to be attributed to the uniformly distributed Cu- and Fe-species on the catalyst surface.
11

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13

Captions of Figures
Table 1: Ullmann-type coupling of 4-iodoanisole to 4,4-dimethoxy biphenyl over Cu-Fe-
hydrotalcite catalyst
Table 2: Influence of the various Bases
Table 3: Influence of the various solvents
Figure 1: XRD profile of as-synthesised Cu-Fe LDH as a function of temperature
Figure 2: SEM images and of as-synthesized Cu-Fe layered double hydroxide and after
calcination and EDX spectra of Cu-Fe layered double hydroxide.
Figure 3: Thermo gravimetric data of as synthesised Cu-Fe LDH (1) and calcined Cu-Fe
MMO (2)
Figure 4: XPS core level spectra of Cu2p (A), O1s (B) and Fe2p (c) from Cu-Fe layered
double hydroxide after calcination.
Scheme 1: C-C coupling of aryl halides
14

Table 1: Results of Ullmann coupling of substituted aryl halides over Cu-Fe MMO
catalyst at 120 °C [reaction mixture = 2 mmol aryl halide (with or without 2
mmol of second aryl halide) + 5 ml DMF + 3 mmol Base + catalyst (10 wt% w.r.to
aryl halide)]
Entry
Reaction Time
Substrates
Product
Yield
(%)
(h)
5
1
2
p-Iodoanisole
4,4’-Dimethoxy-biphenyl
80
78
Iodobenzene
5
Biphenyl
3
4
5
6
P-Bromoanisole
p-chloroanisole
p-Fluroanisole
p-Iodoanisole
12
20
20
5
4,4’-Dimethoxy-biphenyl
4,4’-Dimethoxy-biphenyl
4,4’-Dimethoxy-biphenyl
4,4’-Dimethoxy-biphenyl
50
5
nil
78a
<5b
45c
nild
7
8
9
p-Iodoanisole
p-Iodoanisole
p-Iodoanisole
20
20
20
4,4’-Dimethoxy-biphenyl
4,4’-Dimethoxy-biphenyl
4,4’-Dimethoxy-biphenyl
aFifth time reuse of the catalyst,
bIn the absence of catalyst : control
c Reaction temperature 100 °C
dAt Room temperature to 50 °C
15

Table 2: Results of Ullmann coupling of 4-iodoanisole to afford 4,4’-dimethoxybiphenyl in
the presence of different bases at 120 °C [reaction conditions = 2 mmol
iodoanisole + 3mmol base + 5ml DMF + catalyst (10 wt % w.r.to 4-iodoanisole)
Base used
Reaction time
Product yield
(hrs)
20
20
20
20
20
6
(%)
29
25
10
5
Sodium Acetate
Sodium Carbonate
Triethyl amine
Pyridine
Zinc dust
30
80
Potassium carbonate
16

Table 3: Results of Ullmann coupling of 4-iodoanisole to afford 4, 4’-dimethoxybiphenyl in
the presence of different solvents at reflux temperature [reaction conditions = 2
mmol 4-iodoanisole + 3 mmol K2CO3 + 5 ml solvent + catalyst (10 wt % w. r. to 4-
iodoanisole]
Reaction time
(h)
Product yield
Solvent used
(%)
80
20
6
DMF
NMP
6
10
12
20
20
20
12
Xylene
Water
--
Toluene
1, 4-Dioxan
Acetonitrile
5
--
17
17

Figure 1: XRD profile of as-synthesised Cu-Fe layered double hydroxide as a function of
temperature
18

Figure 2: SEM images and of as-synthesized Cu-Fe layered double hydroxide and after
calcination and EDX spectra of Cu-Fe layered double hydroxide.
19

Figure 3: Thermo gravimetric data of as synthesised Cu-Fe layered double hydroxide (1) and
calcined Cu-Fe layered double hydroxide (2)
20

Figure 4: XPS core level spectra of Cu2p (A), O1s (B) and Fe2p (c) from Cu-Fe layered
double hydroxide after calcination.
21

Scheme 1: Ullmann coupling reaction of aryl halides
22

Graphical Abstract
Cu-Fe MMO
DMF, K2CO3
Mixed metal oxide derived from CuFe layered double hydroxide was demonstrated to be an
efficient catalyst for Ullmann coupling between aryl halides to synthesize biaryls.
23