Regioselective side-chain as well as nuclear monobromination of aromatic substrates with N-bromosuccinimide using phosphotungstic acid supported on zirconia as a heterogeneous catalyst

Article abstract of DOI:10.1016/j.molcata.2003.09.008

Regioselective monobromination of aromatic substrates with N-bromosuccinimide has been achieved in excellent isolated yields (84-98%) using phosphotungstic acid supported on zirconia as a novel heterogeneous catalyst. The catalyst has been characterized by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), surface area and acidity measurements. Remarkably, the new catalyst system described brought about the side-chain bromination of aromatics to afford bromomethyl arenes in excellent yields (86-98%) without the need for a radical initiator. Recovery and recylability of the catalyst have been well established.

Full text of DOI:10.1016/j.molcata.2003.09.008

Journal of Molecular Catalysis A: Chemical 210 (2004) 165–169
Regioselective side-chain as well as nuclear monobromination of aromatic
substrates with N-bromosuccinimide using phosphotungstic acid
supported on zirconia as a heterogeneous catalyst
∗
R. Rajagopal, S.A. Siddiqui, Thomas Daniel, R.J. Lahoti, K.V. Srinivasan
National Chemical Laboratory, Division of Organic Chemistry Technology, Dr. Homi Bhabha Road, Pune 411 008, India
Received 20 May 2003; received in revised form 11 September 2003; accepted 11 September 2003
Abstract
Regioselective monobromination of aromatic substrates with N-bromosuccinimide has been achieved in excellent isolated yields (84–98%)
using phosphotungstic acid supported on zirconia as a novel heterogeneous catalyst. The catalyst has been characterized by means of X-ray
diffraction (XRD), scanning electron microscopy (SEM), surface area and acidity measurements. Remarkably, the new catalyst system
described brought about the side-chain bromination of aromatics to afford bromomethyl arenes in excellent yields (86–98%) without the need
for a radical initiator. Recovery and recylability of the catalyst have been well established.
©
2003 Elsevier B.V. All rights reserved.
Keywords: Bromination; N-Bromosuccinimide; Phosphotungstic acid; Zirconia; Regioselective
1
. Introduction
2. Experimental
Brominated arenes are versatile intermediates in the syn-
2.1. Materials and equipment
thesis of a wide variety of biologically active compounds [1].
They are widely used for the preparation of products of com-
mercial importance such as pharmaceuticals, agrochemicals,
synthetic colorants and performance chemicals. A popular
and inexpensive reagent often used for aromatic bromina-
tion is N-bromosuccinimide (NBS) in CCl4 [2]. A variety
of methods for bromination of aromatics with NBS have
been reported in the literature ranging from NBS-H2SO4
All the chemicals, reagents and solvents were of LR grade
procured from Merck and Lancaster, and used as such.
Infra-red spectra were recorded with ATI MATT-SON
RS-1 FTIR spectrometer. Proton NMR spectra were
recorded on Bruker AC-200 machine in CDCl3 with TMS
as an internal standard. Mass spectra were obtained with
Finnigen MAT mass spectrometer. The diffractogram of
X-ray powder diffraction pattern was recorded on a Rigaku
diffractometer model D/max. IIIVC with N-filtered Cu K␣
radiation. Determination of surface area was carried out
by Brunner–Emmett–Teller (BET) N2 adsorption using a
Omnisorp 100CX apparatus.
[3], NBS-SiO2 [4], NBS-pTSA [5], NBS-amberlyst [6],
NBS-NaOH [7], and NBS-HBF4/Et2O [8]. In recent times,
we have reported the use of NBS-HZSM-5 [9], NBS-
ultrasound [10] and NBS-ionic liquid [11] for this method-
ology. In continuation, this paper reports for the first time,
regioselective high yielding nuclear and more particularly
side-chain bromination of activated aromatic substrates with
NBS in the presence of phosphotungstic acid impregnated
on zirconia (PTZ) as a new heterogeneous catalyst using
methanol as solvent (Scheme 1).
2
2
.2. Synthesis of the catalyst
.2.1. Synthesis of zirconium hydroxide, Zr(OH)4
Aqueous ammonia (28%) (100 ml) was added dropwise
into a clear solution of zirconyl oxy chloride (ZrOCl2·8H2O)
(100 g) dissolved in distilled water (1000 ml). The white
∗
precipitate (pH 10) was stirred at room temperature for 2 h.
The precipitate was filtered and washed with distilled water
Corresponding author. Tel.: +91-20-5889089; fax: +91-20-5893614.
E-mail address: kvsri@dalton.ncl.res.in (K.V. Srinivasan).
1
381-1169/$ – see front matter © 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2003.09.008

1
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R. Rajagopal et al. / Journal of Molecular Catalysis A: Chemical 210 (2004) 165–169
Table 1
Surface area of PTZ catalyst with different PTA loading
2
PTA loading (%)
Surface area (m /g)
0
5
0
2
5
32
65
78
91
84
1
1
1
Scheme 1.
until chloride free (silver nitrate test). The solid was dried
◦
at 100 C under static air for 12 h to obtain 40 g of pure and
2
amorphous zirconium hydroxide (surface area 140 m /g).
PTZ catalyst with 5, 10, 12 and 15 wt.% loading of phos-
photungstic acid on zirconia were prepared and character-
ized.
2
.2.2. Synthesis of PTZ catalyst
Methanolic solutions of 5, 10, 12 and 15% by weight
of phosphotungstic acid (PTA) calculated with respect to
zirconium hydroxide were prepared in which 1 wt.% of
concentrated phosphoric acid was added. To this mixture
dried zirconium hydroxide powder was added, keeping
methanol:zirconium hydroxide ratio 10:1 and stirred for
3
3
.1. Characterization of the catalyst
.1.1. Surface area measurements
The samples were activated at 573 K for 3 h in high vac-
−
5
uum (10 mm). After the treatment, the anhydrous weights
of the samples were recorded. The samples were then cooled
to 77 K in liquid nitrogen and allowed to adsorb nitrogen gas.
Table 1 shows the BET surface area of PTZ series catalysts.
First entry, i.e. simple zirconia calcined at 750 C showed a
surface area of 32 m /g. At 12% loading of PTA, the surface
area increased by almost three times and was found to reach
a maximum area of 91 m /g. This particular PTZ catalyst
with 12% loading of PTA afforded the optimum results for
the bromination reaction.
1
h. Methanol was evaporated under reduced pressure and
◦
the resulting powder was dried at 120 C for 12 h to afford
the PTZ catalyst for the bromination reaction. The catalyst
was activated by calcinating at 750 C for 4 h.
◦
◦
2
2
.3. A typical procedure for bromination
2
A mixture of aromatic substrate (0.018 mol), NBS
(0.018 mol) and PTZ (5% (w/w)) in methanol (10 ml) was
refluxed for 2 h under vigorous stirring. The completion of
the reaction was followed by TLC using petroleum ether:
ethyl acetate (10:1) as eluent. The reaction mixture was fil-
tered to recover the PTZ catalyst. The catalyst was washed
3
.1.2. X-ray diffraction (XRD)
The X-ray diffraction (XRD) patterns of PTZ catalysts
with different PTA loading calcined at different tempera-
tures are shown in Figs. 1–3. The patterns were recorded in
the region, 10–80 2θ at a scanning rate of 4 min . All the
◦
with methanol and dried at 100 C for 2 h. The dried cat-
alyst could be reused at least three times without loss of
activity.
◦
◦
−1
The filtrate was subjected to distillation under reduced
pressure to remove methanol. The residue was diluted with
water (10 ml). The mixture was then extracted with ethyl ac-
etate (2×10 ml). The combined organic layer was separated,
dried over anhydrous sodium sulphate and the ethyl acetate
was distilled off to afford the TLC pure bromoarenes in al-
most all the cases except for catechol and hydraquinone. For
catechol and hydroquinone, the pure products were isolated
by column chromatogarphy.
o
a-550 C
o
b-650 C
o
c-750 C
o
d-950 C
(
d)
c)
3
. Results and discussion
(
Sulphated metal oxides constitute super acidic catalytic
systems. Hetero-polyacids are highly crystalline solids with
large surface areas and possessing strong acid properties
in solid phase and solution. The present catalytic system
(b)
a)
(
(PTZ) was generated by a combination of the two by sup-
2
0
40
60
80
porting phosphotungstic acid on amorphous zirconium hy-
droxide in the presence of phosphoric acid by the wetness
impregnation technique.
2
θ (degree)
Fig. 1. Five percent PTA loading.

R. Rajagopal et al. / Journal of Molecular Catalysis A: Chemical 210 (2004) 165–169
167
o
a-550 C
o
b-650 C
o
c-750 C
o
d-950 C
(d)
(c)
◦
Fig. 4. SEM image of ZrO2 calcined at 750 C.
(
b)
a)
(
undetectable by XRD. It is well documented that the XRD
pattern of PTA impregnated on freshly prepared SiO2 and
calcined at 400 C showed characteristic peaks of PTA [12].
20
40
60
80
2
θ (degree)
◦
Hence, it can be concluded that PTA is well dispersed on
zirconia surface. Moreover, PTA may have strong interaction
with zirconia on the surface. Small peaks of monoclinic WO3
Fig. 2. 12% PTA loading.
◦
peak positions were corrected with respect to silicon (2θ =
were observed in 12% sample activated at 950 C. These
◦
2
8.4 ), which was used as internal standard. In all the cases
may be due to the breaking up of Keggin hetero-polyanion.
From the calcination temperature required for crystallization
of zirconia, it can be concluded that PTA and phosphoric
acid help to stabilize the catalytically active tetragonal phase
of zirconia and also it retard the formation of monoclinic
phase.
the crystallization of zirconia was complete when the calci-
◦
nation temperature was 750 C and almost pure tetragonal
◦
phase resulted as indicated by the peak at 2θ = 30 . When
◦
the calcination temperature was 950 C, monoclinic phase
begins to appear but in a very low percentage.
There is no indication of crystalline phase related to bulk
◦
PTA which comes as a very strong peak at 2θ = 10 and
3.1.3. Scanning electron microscopy
◦
small peaks at 2θ = 15, 17 and 22 even at a PTA loading
Fig. 4 shows the scanning electron microscopic (SEM)
◦
of 15%. The reason may be that PTA particles are too small
and/or too well dispersed on zirconia surface, which may be
image of zirconia calcined at 750 C. It shows crystalline
particles having average size of 10 nm of monoclinic zir-
conia. The PTA impregnated sample calcined at 750 C re-
◦
sulted in some voids in the structure morphology (Fig. 5).
The tetragonal zirconia (confirmed by XRD) has been seen
as particles of 10 nm. These voids may have resulted from
the phosphation and dehydration of PTA at high calcination
temperature.
o
a-550 C
o
b-650 C
o
c-750 C
(
c)
(
b)
(
a)
20
40
60
80
2θ (degree)
Fig. 3. 15% PTA loading.
Fig. 5. SEM image of 12% PTZ.

1
68
R. Rajagopal et al. / Journal of Molecular Catalysis A: Chemical 210 (2004) 165–169
Table 2
It can be observed that the PTZ catalyst with 12% PTA
loading afforded the best results. It may also be noted that
this is the catalyst which exhibited the maximum surface
area.
Bromination of toluene and anisole using PTZ with different loadings of
PTA
Catalyst
Substrate
Product
Time (h)
Yielda (%)
5
1
1
1
% PTA
0% PTA
2%PTA
Toluene
Anisole
Benzyl bromide
4-Bromoanisole
9
10
97
96
Consequently, a variety of activated aromatic substrates
were reacted with NBS in the presence of PTZ with 12 wt.%
loading of PTA. The time for complete conversion and the
isolated yields of the bromoarenes are recorded in Table 3.
As is evident, the monobromoarenes were obtained in excel-
lent isolated yields. All the bromoarenes isolated are known
compounds reported in literature. Their identities were con-
Toluene
Anisole
Benzyl bromide
4-Bromoanisole
6
8
97
96
Toluene
Anisole
Benzyl bromide
4-Bromoanisole
1.3
1.5
98
97
5% PTA
Toluene
Anisole
Benzyl bromide
4-Bromoanisole
3.5
5
98
98
1
firmed by IR, H NMR and mass spectral analyses. Their
melting points agreed with those reported in literature. The
efficiency of the catalyst system is clearly demonstrated as
can be seen from Table 3, wherein the yields for the catalyzed
reaction is significantly higher in comparison to the uncat-
alyzed one. Benzene, naphthalene, thiophene and chloroben-
zene failed to undergo bromination under the reaction con-
ditions. The catalyst PTZ was recovered by a simple filtra-
a
Isolated yields.
3
.1.4. Acidity
The acidity of catalyst was measured using the reported
Hammet indicator method [13,14]. This was carried out by
exposing a slurry of catalyst (100 mg) in benzene (10 ml) to
a dilute solution of anthraquinone in benzene (1% (w/v)), the
latter being the Hammett indicator. A colour change from
colourless to yellow was observed. It can be concluded that
the acidity of the catalyst has an approximate pKa value of
◦
tion, and after drying at 100 C for 2 h could be recycled at
least three times without loss of activity (Table 4). In all the
recycle batches, the catalyst could be recovered completely
without any loss in weight.
−
8.2.
It was remarkable to observe that the present catalyst sys-
tem promoted the regiospecific side-chain bromination.of
a variety of aromatic substrates (entries 1–7) to afford the
respective bromomethyl arenes in excellent isolated yields
without the need for the addition of a radical initiator. Nor-
mally, the side-chain bromination of such substrates with
NBS require the use of a radical initiator such as benzoyl
peroxide. In all these cases, only the monobrominated prod-
uct could be obtained even if a 2–3 molar excess of NBS
3
.2. Bromination reaction
The catalysts with different loadings of PTZ were tested
by performing the side-chain bromination of toluene and
nuclear bromination of anisole, respectively with NBS. The
reactions were taken to completion as monitored by TLC.
The time for complete conversion and isolated yields of the
bromoarenes are recorded in Table 2.
Table 3
PTZ catalyzed bromination of aromatic substrates with NBS
Entry
Substrate
Product
Time (h)
Yielda (%)
Catalyst
No catalyst
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
Toluene
o-Xylene
m-Xylene
1-Methylnapthalene
BHTc
4-Tolualdehyde
Acetophenone
Anisole
m-Cresol
Catechol
Hydroquinone
2,6-Dimethyl aniline
2-Methyl anisole
1-Napthol
2-Napthol
2-Methoxy naphthalene
Benzyl bromide
1.3
1.5
1.5
2.0
2.0
2.0
2.0
1.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
98
89
87
10
41
11
13
8
10
14
28
31
33
23
30
14
27
23
57
2-Bromomethyltoluene
3-Bromomethyltoluene
1-Bromomethylnapthalene
4-Bromo BHT
4-Bromomethylbenzaldehyde
2-Bromo-1-phenyl-ethanone
4-Bromoanisole
b
86
98
92
93
98
92
4-Bromo-3-methyl phenol
4-Bromo catechol
d
1
1
1
1
1
1
1
86
d
2-Bromo-4-hydroxy phenol
4-Bromo-2,6-dimethyl aniline
4-Bromo-2-methylanisole
4-Bromo-1-hydroxynapthalene
1-Bromo-2-hydroxynapthalene
1-Bromo-2-methoxynapthalene
87
84
87
95
94
96
a
b
c
d
Isolated yields unless indicated otherwise.
Estimated by GC analysis.
2,6-di-tert-Butyl-4-methyl-phenol.
Isolated yields after column chromatography.

R. Rajagopal et al. / Journal of Molecular Catalysis A: Chemical 210 (2004) 165–169
169
Table 4
Bromination of toluene and anisole with recovered PTZ catalysta
Entry
Substrate
Product
Time (h)
Yieldb (%)
Recycle I
Recycle II
Recycle III
1
2
Toluene
Anisole
Benzyl bromide
4-Bromoanisole
1.3
1.5
98
98
97
97
97
97
a
In all recycle batches, the catalyst recovery was 100%.
Isolated yields.
b
was employed in the reaction. All other substrates (entries
–16) underwent nuclear bromination to afford the corre-
Acknowledgements
8
sponding bromoarenes in high regioselectivity and excellent
isolated yields.
R.R. thanks CSIR, New Delhi for a research associateship.
Interestingly, there was no reaction when toluene was
brominated under the reaction conditions in the presence
of a radical quencher such as ␣,␣-azobisiso-butyronitrile
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bromomethyl arenes in excellent yields for a variety of sub-
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