Supported phase-transfer catalysts as selective agents in biphenyl synthesis from haloaryls

Article abstract of DOI:10.1016/S0040-4039(01)01196-0

Coupling of substituted halobenzenes to the respective biphenyls is effected with high selectivity in toluene, using a combination of a reducing agent and a weak base in the presence of catalytic tetrabutylammonium bromide (TBAB) and palladium that are both supported on carbon. The maximum selectivity to biphenyl was achieved when Pd, Na₂CO₃, and TBAB were all supported together on activated carbon. The results are explained with postulation of a physical micro-membrane formed in situ by the phase-transfer catalyst.

Full text of DOI:10.1016/S0040-4039(01)01196-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6117–6119
Supported phase-transfer catalysts as selective agents in biphenyl
synthesis from haloaryls
Sudip Mukhopadhyay,a,† Gadi Rothenberg,b,‡ Nida Qafishehc and Yoel Sassonc,*
aChemical Engineering Department, University of California at Berkeley, Berkeley, CA 94720, USA
bYork Green Chemistry Group, Chemistry Department, The University of York, Heslington, York YO10 5DD, UK
cCasali Institute of Applied Chemistry, Hebrew University of Jerusalem, Jerusalem 91904, Israel
Received 22 June 2001; accepted 4 July 2001
Abstract—Coupling of substituted halobenzenes to the respective biphenyls is effected with high selectivity in toluene, using a
combination of a reducing agent and a weak base in the presence of catalytic tetrabutylammonium bromide (TBAB) and
palladium that are both supported on carbon. The maximum selectivity to biphenyl was achieved when Pd, Na2CO3, and TBAB
were all supported together on activated carbon. The results are explained with postulation of a physical micro-membrane formed
in situ by the phase-transfer catalyst. © 2001 Elsevier Science Ltd. All rights reserved.
The selective reductive coupling reaction1 of haloaryls
to biphenyls is of major interest to process chemists as
these products are important building blocks for
numerous agrochemicals and pharmaceuticals.2 Unfor-
tunately, selectivity is generally low due to the parallel
reduction reaction.3,4 However, the reductive coupling
of haloaryls benefits from simple reactor design and
easy catalyst separation and recycling. We have recently
demonstrated the reductive coupling of haloaryls in
water by using formate salts,5 hydrogen gas,6 and/or
zinc powder7 as the reducing agent in the presence of a
base and catalytic amounts of a phase-transfer catalyst
(PTC).8,9 Our goal was to minimize the reduction side
reaction in order to increase the selectivity to biphenyl.
Although the effects of PTC on this reaction have been
reported over 25 years ago, the function of the PTC in
this system is still unclear. Recently, Tundo and co-
workers reported10 the Pt/C-catalyzed hydrodehalo-
genation of halogenated aryl ketones in presence of
PTC. It was proposed that the PTC may adsorb on the
catalyst and embody it, thus changing the micro-envi-
ronment in the vicinity of the Pd catalyst. This hypoth-
esis may further our understanding of the role of PTC
in similar type of reactions. In applying this concept to
our model Pd-catalyzed coupling system, we first tried
to understand the difference between a PTC in solution
and a supported one. Surprisingly, the supported sys-
tem turned to be most effective, achieving very high
yields to biphenyl. Here, we present the results and
discuss how the PTC distribution over the porous car-
bon support could turn the reaction chemoselectively
towards the coupling side.
In a typical reaction,11 the halobenzene and the reduc-
ing agent were stirred in the presence of the catalyst
and a base to give biphenyl as the major product,
together with minor amounts of benzene (the by-
product due to the parallel reduction reaction). No
other products were observed. Conversions and
product selectivities for various halobenzenes are shown
in Table 1.
Carbon was the obvious support of choice due to its
high surface area and porosity, plus of course its high
selectivity as a support in previous Pd-catalyzed reduc-
tive coupling studies. Using carbon-supported PTC,12
Table 1. Coupling reaction with different starting
materiala
Substrate
Time (h)
Conv. (%)
ArꢀAr
ArH
Chlorobenzene
Bromobenzene
Iodobenzene
8.5
8
6
100
100
100
83
92
93
17
8
7
* Corresponding author. Fax (+972) 2 6528250; e-mail: ysasson@
vms.huji.ac.il
a Reaction conditions: Substrate, 16 mmol; support 3 (see Ref. 12),
HCOONa, 19 mmol, temperature, 110°C; agitation speed, 900 rpm;
solvent, PhMe (total volume 50 mL).
† E-mail: sudip@uclink2.berkeley.edu
‡ E-mail: gr8@york.ac.uk
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01196-0

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S. Mukhopadhyay et al. / Tetrahedron Letters 42 (2001) 6117–6119
The basic reactions in this reductive coupling system
are depicted by Eqs. (1)–(5).
an increased product selectivity was observed (cf. Table
2, entries 1–3).
2C6H5Br+Pd“C6H5ꢀC6H5+PdBr2
HCO2 −+H2O“PdHCO3 −+H2
H2+PdBr2“Pd+2HBr
(1)
(2)
(3)
(4)
(5)
When Na2CO3, TBAB, and Pd were all together sup-
ported on carbon, the rate and selectivity obtained were
very high under the reaction conditions (Table 2,
entries 4 and 5), while depositing the formate on the
carbon support together with the other components
resulted in a low selectivity to biphenyl due to an
increase in reduction rate (Table 2, entry 6).
H2+Pd“Pd2+(H−)2
Pd2+(H−)2+C6H5Br“Pd2+(H−)(Br−)+C6H6
The main difference between the reductive coupling and
the reduction is that the homocoupling requires only
electrons, while the reduction requires hydrogen atoms.
As has been shown before,5,13 the selectivity to the
coupling products depends on the number of vacant
active Pd(0) sites, which in turn reflects the balance
between the reduction of Pd(II) (Eq. (3)), and the
formation of Pd(II)(H−)2 via Eq. (4). The latter reaction
is a function of the available dihydrogen concentration
close to the active catalyst surface. From the results of
the present study, it appears that the reactions shown in
Eqs. (4) and (5) are somehow suppressed to give a
higher selectivity to biphenyl. This could be due to the
formation of a physical PTC micro-membrane in the
vicinity of Pd which can allow the passing of electrons
but restricts the hydride formation rate by limiting the
formate adsorption on the surface.10 The marked
increase in reaction time (from 6 to 8 h) when com-
pared to the usual solution PTC reaction may indicate
such adsorption limitations on the catalyst surface in its
surface modified form. The low selectivity to biphenyl
that was obtained when using the formate salt on the
support clearly points out the fact that there was some
extra resistance created on the Pd surface for the solu-
tion formate to get adsorbed when formate was admin-
istered in solution, thus limiting the effective hydride
concentration. Moreover, when the components are
supported on the carbon, there is a chance of adsorp-
tion of a fractional portion of PTC on the Pd surface
during the catalyst preparation and prior to the reac-
tion. The adsorbed PTC species could form a micro-
membrane around the Pd catalyst (Fig. 1). However, to
form a PTC membrane more effectively, the PTC
should be present in close proximity with the solid Pd
catalyst, i.e the PTC should be absorbed on the Pd
surface prior to the reaction. In our opinion, that might
be the crucial deciding factor in terms of selectivity. To
establish this concept, we performed a reaction similar
to that in Table 2 (entry 1) where the PTC and the
support 1 were stirred in toluene for 3 h prior to the
addition of bromobenzene and formate salt. After the
stipulated 6 h reaction period, 52% selectivity to the
biphenyl was observed. The increase in product selectiv-
ity from 34 to 52% could be due to the formation of the
PTC membrane prior to the reaction which provides an
extra resistance gradient to the incoming formate
molecules from the solution to the Pd surface and thus
limiting the hydride formation.
The amount of water present turned out to be most
crucial parameter for this reaction. It has been shown
elsewhere3 that water molecules should also be
adsorbed on the Pd surface and will generate hydrogen
from reaction with formate salt. In all the reactions,
0.15 g of water was added to get a faster rate and
maximum selectivity. When the water amount was fur-
ther increased to 0.75 g, the selectivity decreased
abruptly due to the leaching of PTC from the support.
A separate set of experiments has been performed to
elucidate the effect of water on the leaching time of
PTC from the surface. It was observed that when the
water amount was >0.5 g, the leaching had started.
However, at a water amount of 3 g, 67% of the PTC
was leached out from the surface in 1 h. Thus, the
water amount used in all our experiments (0.15 g) is
within the safe limit with regard to leaching.
The solid Pd/C catalyst was recycled without losing any
catalytic activity by simply stirring it with hot water,
followed by filtration and washing with methanol. The
same carbon support and Pd were then used to support
a fresh batch of PTC, which retained almost the same
catalytic activity in the reusability experiments.
Table 2. Coupling reaction with different starting
materiala
Entry
Support
Time (h)
Conv. (%)
Select. (%)
ArꢀAr
1b
2
3
4
5
Support 1
Support 2
Support 2A
Support 3
Support 3A 7.5
Support 4
6
6.5
6
100
100
100
100
100
100
34
79
75
92
89
56
8
6
4
a Reaction conditions: Bromobenzene, 2.5 g (16 mmol), Na2CO3, 2.5
g (24 mmol), sodium formate, 1.3 g (19 mmol), solvent, PhMe (total
reaction volume 50 mL), temperature, 110°C.
b TBAB, 0.2 g (0.6 mmol).
To determine if there were any chemical changes occur-
ring on the surface of the Pd, IR and XRD were
performed on the catalyst before and after reaction.
Figure 1. Cartoon of the PTC membrane hypothesis.

S. Mukhopadhyay et al. / Tetrahedron Letters 42 (2001) 6117–6119
6119
Similar patterns were obtained in each case, supporting
our hypothesis that this is a physical adsorption phe-
nomena. Moreover, the catalyst retained its activity
when re-used, and the same product selectivity was
obtained, irrespective of the reducing agent employed
(e.g. with molecular hydrogen, 82% selectivity to
biphenyl was achieved).
9. Mukhopadhyay, S.; Rothenberg, G.; Wiener, H.; Sasson,
Y. New. J. Chem. 2000, 24, 305.
10. Selva, M.; Tundo, P.; Perosa, A. J. Org. Chem. 1998, 63,
3266.
11. Typical experimental procedure: Sodium formate (19
mmol), support 3 (3 g) (vide infra), 0.15 g water, and
toluene (total volume 50 mL) were mixed together in a
300 mL autoclave. Reaction progress was monitored by
GC. After 6–10 h at 110°C, the mixture was cooled and
diluted with water and the toluene layer was evaporated
to get crude biphenyl. Recrystallization of the crude
product afforded 84 mol% of biphenyl14 based on
C6H5Br.
12. Procedure for the preparation of Support 3: Na2CO3, 2.5
g (24 mmol), TBAB, 0.2 g (6.2×10−4 mol), 0.5 g of 5%
Pd/C, and 2.525 g activated charcoal were taken in a
glass reactor with 50 mL water and stirred vigorously for
3 h. The mixture was then taken to the rotavapor and
dried completely under 10 mm vacuum at 70°C. The
residual solid was then dried in a vacuum drier at 40°C
for 70 h. The other supports were prepared in a similar
manner. Support 1: Pd was supported on activated char-
coal; Support 2: TBAB and Pd were both supported on
carbon; Support 2A: TBAB was supported on carbon
and then the solid powder mixed with Pd/C; Support 3A:
similar to support 3 but the Pd/C was externally mixed
with the TBAB and base supported material; Support 4:
sodium formate was also supported together with the
other component on Support 3.
13. A similar mechanistic approach was suggested for the
Pd-catalyzed coupling of halopyridines. See: Munavalli,
S.; Rossman, D. I.; Szafraniec, L. L.; Beaudry, W. T.;
Rohrbaugh, D. K.; Ferguson, C. P.; Gra¨tzel, M. J. Fluor.
Chem. 1995, 73, 1.
14. For a detailed description of materials and instrumenta-
tion, including the characterization of reference materials,
see (a) Mukhopadhyay, S.; Rothenberg, G.; Sasson, Y.
Adv. Synth. Catal. 2001, 343, 274; (b) Tamura, Y.; Chun,
M.-W.; Inoue, K.; Minamikawa, J. Synthesis 1978, 822.
In conclusion, supporting the PTC on activated carbon
can minimize the occurrence of hydrodehalogenation.
This permits the usage of a weak base, such as Na2CO3,
thus making this process attractive from the standpoint
of cost and waste-disposal concerns. However, much
work is still needed to draw a precise explanation of
this phenomenon.
References
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4. Marques, C. A.; Selva, M.; Tundo, P. J. Org. Chem.
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5. Mukhopadhyay, S.; Rothenberg, G.; Gitis, D.; Wiener,
H.; Sasson, Y. J. Chem. Soc., Perkin Trans. 2 1999, 2481.
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