Greener Ullmann-type coupling of aryl halides for preparing biaryls using reusable Pd/ZrO2 catalyst

Article abstract of DOI:10.1080/00397910903531805

Biaryls with excellent yields can be prepared by the Ullmann-type coupling of aryl halides in the presence of potassium carbonate (as a base) and dimethylformamide (as a solvent), at 140°C, using a reusable Pd (2.5wt%)/ZrO₂ catalyst. The product yield of 4-iodoanisole coupling is strongly influenced by the catalyst preparation method, solvent, and base. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903531805

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Greener Ullmann-Type Coupling of
Aryl Halides for Preparing Biaryls Using
Reusable Pd/ZrO Catalyst
Deepa K. Dumbre , Radhika D. Wakharkar & Vasant R. Choudhary
a
2
a
b
a
Chemical Engineering and Process Development Division, National
Chemical Laboratory , Pune, India
b
Division of Organic Chemistry, National Chemical Laboratory ,
Pune, India
Published online: 15 Dec 2010.
To cite this article: Deepa K. Dumbre , Radhika D. Wakharkar & Vasant R. Choudhary (2010) Greener
Ullmann-Type Coupling of Aryl Halides for Preparing Biaryls Using Reusable Pd/ZrO Catalyst,
2
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 41:2, 164-169, DOI: 10.1080/00397910903531805
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1
Synthetic Communications , 41: 164–169, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903531805
GREENER ULLMANN-TYPE COUPLING OF ARYL
HALIDES FOR PREPARING BIARYLS USING REUSABLE
Pd/ZrO CATALYST
2
1
Deepa K. Dumbre, Radhika D. Wakharkar, and
2
1
Vasant R. Choudhary
1
Chemical Engineering and Process Development Division, National
Chemical Laboratory, Pune, India
2
Division of Organic Chemistry, National Chemical Laboratory, Pune, India
Biaryls with excellent yields can be prepared by the Ullmann-type coupling of aryl halides in
the presence of potassium carbonate (as a base) and dimethylformamide (as a solvent), at
ꢀ
1
coupling is strongly influenced by the catalyst preparation method, solvent, and base.
40 C, using a reusable Pd (2.5 wt%)/ZrO
2
catalyst. The product yield of 4-iodoanisole
2
Keywords: Aryl halides; biaryls; Pd=ZrO ; Ullmann coupling reaction
INTRODUCTION
Biaryls play an important role in modern organic chemistry. Ullmann coupling
of two aryl halide molecules with the elimination of two halogen atoms is considered
one of the most important methods for the formation of the CꢁC bond, particularly
in the synthesis of biaryls.
In the Ullmann reaction, two molecular equivalents of aryl halide are reacted
ꢀ
with one equivalent of finely divided copper at high temperature (>200 C) to form a
biaryl and a copper halide. This reaction with different variants has been thoroughly
[1–3]
[4]
Recently, Hassan et al. have reviewed comprehensively
reviewed by Fanta.
aryl–aryl bond formation one century after the discovery of the Ullmann reaction.
A large number of studies have been reported for aryl–aryl bond formation using
copper as a reagent (in stoichiometric amounts) or catalyst and also using nickel
as a promoter. Use of the reagent or catalyst, however, produced lot of waste,
and these cannot be reused. Hence, there is a need to develop an environmentally
friendly catalyst that can be easily separated and reused for the reaction.
Pd-containing complex catalyst systems, such as Pd=C with zinc in the presence
[5]
of water and liquid carbon dioxide and Pd (OCOCF )=P(2-furyl) in supercritical
3
[6]
carbon dioxide, have been reported for the Ullmann-type coupling reactions.
Received September 3, 2009.
Address correspondence to Dr. Vasant R. Choudhary, Chemical Engineering and Process
Development Division, National Chemical Laboratory, Pune 411 008, India. E-mail: vr.choudhary@
ncl.res.in
1
64

ULLMANN COUPLING REACTION
165
Palladium-catalyzed coupling of Grignard reagents or metal (viz., zinc, mercury,
silicium, germanium, lead, bismuth, antimony, copper, zirconium, indium, tin,
[
4]
etc.) derivatives have also been employed extensively for aryl–aryl bond formation.
However, these palladium-catalyzed reactions are complex, require expensive
reagents, and are difficult to perform. Moreover, because they create a lot of waste,
these are also not environmentally friendly reactions. It would therefore be very
interesting if a simple but easily separable and reusable palladium catalyst could
be developed for the Ullmann-type coupling reaction. This has been achieved in
the present investigation. In this communication, we report a greener process for
the Ullmann-type aryl–aryl coupling of aryl iodides or bromides, forming biaryls
ꢀ
with excellent yields at low temperature (140 C) in the presence of potassium car-
bonate and dimethylformamide (DMF), using easily separable and reusable
zirconia-supported palladium catalyst.
RESULTS AND DISCUSSION
The performance of Pd=ZrO catalysts [prepared by different methods, viz.
2
impregnation, coprecipitation, deposit precipitation (DP), and homogenous deposit
precipitation (HDP)] in the Ullmann-type coupling of 4-iodoanisole is shown in
Table 1.
The results (Table 1) show a strong influence of the catalyst preparation
method on the product yield in the Ullmann-type coupling reaction. The catalyst
prepared by the impregnation technique showed the best performance (85% product
yield). The poorest performance was shown by the catalyst prepared by the copreci-
pitation method, which is most probably because a large part of the Pd (which is bur-
ied in the bulk of the catalyst) is not available for the reaction. The catalysts
prepared by the DP and HDP methods show intermediate activity in the reaction,
even though their Pd particles are smaller in size. Their lesser activity is therefore
expected, mostly because of the lower Pd loading in these catalysts (Table 1).
Results showing the Ullmann-type coupling of different aryl halides to
corresponding biaryls (Scheme 1) over the Pd=ZrO2 catalyst (prepared by the
impregnation technique) in the presence of DMF (as a solvent) and K CO (as a
2
3
base) are presented in Table 2. In the absence of any catalyst, the product yield in
the coupling of 4-iodoanisole for 15 h was quite small (<5%).
The results (Table 2) show that the product yield in the Ullmann-type coupling
of aryl iodides is quite high (>80%). As expected, the product yield in the case of
0
Table 1. Ullmann-type coupling of 4-iodoanisole to 4,4 -dimethoxy biphenyl over Pd=ZrO
prepared by different methods
2
catalyst
Catalyst preparation
method
Pd loading in
catalyst (wt%)
Pd particle
size (nm)
Reaction
time (h)
Isolated product
yield (%)
Impregnation
Coprecipitation
DP
2.5
2.5
1.2
1.5
16
—
9
5
10
12
8
85
16
37
43
HDP
8

166
D. K. DUMBRE, R. D. WAKHARKAR, AND V. R. CHOUDHARY
Scheme 1. Ullmann-type coupling reaction.
the coupling of aryl bromide (entry 5) is smaller (46% for bromoanisole). In the
simultaneous coupling of p-iodoanisole and trimethoxyiodobenzene (entry 3), there
was no hetero coupling. However, in the simultaneous coupling of p-iodoanisole
and iodobenzene (entry 6), hetero coupling to small extent (12% yield for 4-imethoxy-
biphenyl) is observed. The results show a strong influence of the substitutent in the
aryl halide on the Ullmann-type coupling reaction. In general, the catalyst showed
high activity for the Ullmann-type coupling reaction. Apart from its high activity,
2
Table 2. Ullmann-type coupling of aryl halides over the Pd=ZrO catalyst (prepared by the impregnation
method)
Reaction
time (h)
Entry
Substrates
p-Iodoanisole
Iodobenzene
Product
Yield (%)
0
1
2
5
7
4,4 -Dimethoxy-biphenyl
Biphenyl
85
88
p-Iodoanisole þ 3,4,5-
64 (A) þ 25
3
4
5
5
trimethoxyiodobenzene
(B)
3,4,5-Trimethoxyiodobenzene
80
46
5
6
P-Bromoanisole
15
7
0
p-Iodoanisole þ iodobenzene
4,4 -Dimethoxy-biphenyl A) þ biphenyl 64 (A) þ 21
(
B) þ 4-methoxy-biphenyl (C)
(B) þ 12(C)
a
0
7
8
9
p-Iodoanisole
15
8
4,4 -Dimethoxy-biphenyl
4,4 -Dimethoxy-biphenyl
<5
83
39
nil
b
0
0
0
p-Iodoanisole
c
p-Iodoanisole
20
20
4,4 -Dimethoxy-biphenyl
4,4 -Dimethoxy-biphenyl
d
1
0
p-Iodoanisole
a
b
c
In the absence of catalyst.
Fourth reuse of the catalyst.
ꢀ
At 100 C.
At 0 or 50 C.
d
ꢀ

ULLMANN COUPLING REACTION
167
0
Table 3. Ullmann-type coupling of 4-iodoanisole to 4, 4 -dimethoxy biphenyl over Pd=ZrO
pared by the impregnation technique) in the presence of different bases or solvents
2
catalyst (pre-
Base
Solvent
Reaction time (h) Isolated product yield (%)
K
Na
2
CO
3
DMF
DMF
5
20
20
20
20
20
10
12
12
20
85
20
25
10
5
2
CO
3
NaOAC
DMF
DMF
Triethylamine
Pyridine
Zinc dust
DMF
DMF
30
19
14
<5
nil
K
K
K
K
2
CO
2
CO
2
CO
2
CO
3
3
3
3
NMP
Acetonitrile
Xylene
Ethanol, 1,4-dioxane, toluene, or water
the catalyst also showed excellent reusability in the coupling of 4-iodoanisole
Table 2). In the first, second, third and fourth reuse of the catalyst in the reaction,
the product yields were 84, 84, 83, and 83%, respectively.
We have also studied the influence of reaction temperature (0–140 C) on the coup-
(
ꢀ
ꢀ
ꢀ
ling of 4-iodoanisole. Up to 50 C, there was almost no reaction for 20 h, but at 100 C
ꢀ
(
for 20 h) and 140 C (for 5 h) the product yields were 39 and 85%, respectively (Table 2).
We have observed a strong influence of both the solvent and base on the
Ullmann-type coupling reaction (Table 3) as follows. DMF was found to be the best
solvent for the coupling of 4-iodoanisole. There was little or no reaction in the pres-
ence of ethanol, 1,4-dioxan, toluene, or water as solvents. However, for solvents,
such as N-methyl pyrrolidone (NMP), xylene, and acetonitrile, the product yields
were 19, 3, and 14%, respectively. Also, when K CO was replaced by Na CO ,
2
3
2
3
NaOAC, trimethyl amine, pyridine, or zinc dust in the coupling of 4-iodoanisole,
the product yield was much smaller. It was 20, 25, 10, 5, and 30%, respectively, even
Scheme 2. Plausible mechanism of Ullmann-type coupling of aryl halide over Pd=ZrO
2
catalyst in the
presence of K CO
2
3
.

168
D. K. DUMBRE, R. D. WAKHARKAR, AND V. R. CHOUDHARY
though the reaction time was longer (20 h). This revealed that among the bases,
K CO is the most suitable base for the reaction.
It has long been known that the Ullmann reaction of substituted aryl halides
2
3
results in the formation of biaryl bonds only at the carbon atom from which the
reactive halogen has been displaced. The possible mechanism of Ullmann coupling
of aryl halide over the Pd=ZrO catalysts is shown in Scheme 2.
2
The coupling reaction seems to involve two steps: first an oxidative addition of
catalyst to the aryl halide leads to the formation of an activated complex, which
reacts preferentially with the second halide to form a diarylated palladium moiety.
In the second step, a reductive elimination gives the biaryl product and the Pd(0)
species to complete the catalytic cycle.
EXPERIMENTAL
The Pd=ZrO2 catalyst (Pd loading ¼ 2.5 wt%) was prepared by depositing
PdCl from its aqueous acidic (HCl) solution on zirconia support (prepared from zir-
2
conium nitrate by its hydrolysis with ammonium hydroxide, followed by washing
ꢀ
and drying the zirconium hydroxide and then calcining it at 500 C for 3 h) by the
incipient wetness impregnation technique. After impregnation, the wet catalyst mass
ꢀ
ꢀ
was dried at 100 C for 4 h and then calcined in static air in muffle furnace at 500 C
for 3 h. The resulting catalyst mass was further treated with an ammoniacal solution
of hydrazine on a water bath for transforming the Pd(0) (from the catalyst) to met-
allic Pd. The catalysts were also prepared by the coprecipitation (using ammonium
hydroxide as precipitating agent), DP (using NaOH as precipitating agent), and
HDP (using homogenously formed NH OH as precipitating agent) methods,
4
followed by the pretreatment similar to that used for the catalyst prepared by the
7]
impregnation technique. The latter methods are described elsewhere.
[
The presence of the metallic Pd phase in the reduced catalysts was confirmed
by x-ray diffraction. The particle size of Pd in the catalysts was determined by their
transmission electron microscopic (TEM) examination.
In a typical experiment, the reaction was carried out under the following reac-
tion conditions: reaction mixture ¼ 2.5 mmol aryl halide (with or without 2.5 mmol
of second aryl halide) þ 5 ml DMF (as a solvent) þ 3.62 mmol potassium carbonate
ꢀ
(
as a base) þcatalyst (10 wt% of aryl halide), temperature ¼ 140 C and reaction
time ¼ 6–20 h. The reaction was monitored by thin-layer chromatography (TLC).
After completion of reaction, the catalyst was separated by filtration. Then the fil-
trate was quenched 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.
0
1
4
,4 -Dimethoxy-biphenyl: H NMR (CDCl þ CCl 50 MHz): d 7.47 (d, 4H,
3 4,
3
4.
1
3
J ¼ 8 Hz), 6.95 (d, 4H, J ¼ 8 Hz), 3.85 (s, 6H); C NMR (CDCl þ CCl 50 MHz):
d 158.7 (2C), 133.5 (2C), 127.7 (4C), 114.2 (4C), 55.2 (2C); IR (chloroform): 3019,
ꢁ
1
957, 1608, 1500, 1215, 1182, 1041, 824 cm ; GC mass: m=z 214.
2
In conclusion, the zirconia-supported Pd (prepared by the impregnation
method) is a highly active and environmentally friendly (easily separable, reusable,

ULLMANN COUPLING REACTION
169
and also nontoxic) catalyst for the Ullmann-type coupling of aryl iodides or bro-
mides with high product yields in the presence of DMF (as a solvent) and K CO
2
3
(as a base). The catalytic performance of Pd=ZrO in the reaction is strongly influ-
ence by the method of catalyst preparation and also by the base and=or solvent used
2
in the reaction.
ACKNOWLEDGMENT
V. R. C. is grateful to the National Academy of Sciences (India) for the NASI
Senior Scientist Platinum Jubilee Fellowship.
REFERENCES
1
2
3
4
. Fanta, P. E. The Ullmann synthesis of biaryls. Chem. Rev. 1945, 38, 139.
. Fanta, P. E. The Ullmann synthesis of biaryls. Chem. Rev. 1964, 64, 613.
. Fanta, P. E. The Ullmann synthesis of biaryls. Synthesis 1974, 9.
. Hassan, J.; Sevignon M.; Gozzi, C.; Schuly, E.; Lemaire, M. Aryl-aryl bond formation one
century after the discovery of the Ullmann reaction. Chem. Rev. 2002, 102, 1359.
. Li, J.; Xie, Y.; Jiang, H.; Chen, M. Palladium-catalyzed Ullmann-type coupling with zinc in
5
6
7
the presence of H O in liquid carbon dioxide. Green Chem. 2002, 4, 424.
2
. Shezad, N.; Clifford, A. A.; Rayner, M. Pd-catalyzed coupling reactions in supercritical
carbon dioxide and under solventless condition. Green Chem. 2002, 4, 64.
. Dumbre, D. K. Selective liquid phase alcohol oxidation and Heck-type coupling reactions
using heterogenous catalysts. PhD thesis, University of Pune, Pune, 2008.