Regioselective bromination of aromatic compounds with Br 2/SO2Cl2 over microporous catalysts

Article abstract of DOI:10.1016/j.tetlet.2005.04.116

A new selective brominating system Br₂/SO₂Cl ₂/zeolite, has been discovered. Partially cation-exchanged Ca ²⁺-Y zeolite efficiently catalyzes the selective para-bromination of neat chlorobenzene (CB) by Br₂/SO₂Cl₂ affording a CB conversion of ～89% and a para-selectivity of ～97%. During the bromination reaction, SO₂Cl₂ oxidizes HBr, prevents its accumulation within the zeolite pores and yields a more active brominating species. The Ca²⁺-Y catalyst was found to be stable under the bromination conditions, and can easily be regenerated by calcination. The Br₂/SO₂Cl₂/Ca²⁺-Y brominating system could be applicable to other activated aromatic compounds such as o-xylene, toluene and fluorobenzene.

Full text of DOI:10.1016/j.tetlet.2005.04.116

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4465–4468
Regioselective bromination of aromatic compounds with
Br2/SO2Cl2 over microporous catalysts
Jallal M. Gnaima,* and Roger A. Sheldonb
aDepartment of Chemistry, The Triangle Regional R&D Center, PO Box 2167, Kfar-Qari 30075, Israel
bDepartment of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands
Received 6 March 2005; revised 4 April 2005; accepted 26 April 2005
Available online 17 May 2005
Abstract—A new selective brominating system Br2/SO2Cl2/zeolite, has been discovered. Partially cation-exchanged Ca2+-Y zeolite
efficiently catalyzes the selective para-bromination of neat chlorobenzene (CB) by Br2/SO2Cl2 affording a CB conversion of ꢀ89%
and a para-selectivity of ꢀ97%. During the bromination reaction, SO2Cl2 oxidizes HBr, prevents its accumulation within the zeolite
pores and yields a more active brominating species. The Ca2+-Y catalyst was found to be stable under the bromination conditions,
and can easily be regenerated by calcination. The Br2/SO2Cl2/Ca2+-Y brominating system could be applicable to other activated
aromatic compounds such as o-xylene, toluene and fluorobenzene.
Ó 2005 Elsevier Ltd. All rights reserved.
The manufacture of many bulk and fine chemicals in-
volves bromination of aromatics.1 Various methods
have been developed and reported for the bromination
of aromatic systems using a variety of brominating
agents under various reaction conditions.2 Some of these
methods involve the use of Br2/Lewis acids,3 Br2/SbF3/
HF,4 NBS/H2SO4/CF3CO2H,5 NBS/PTSA,6 NBS/
NaOH,7 NBS in ionic liquids,8 HBr/tert-BuOOH,
HBr/H2O2,9 HBr/DMSO,10 NH4Br/H2O2/CH3COOH,11
quaternary ammonium tribromide,12 KBrO3,13 KBr/so-
dium tungstate/H2O2,14 hexamethylene tetramine tribro-
mide,15 pyridinium hydrobromide perbromide,16 NaBr/
Oxone, KBr/Oxone, KBr/H2O2/Oxone,17 CuBr2/t-BuO-
NO,18 sodium monobromoisocyanurate19 and the cata-
lytic oxidation of bromide ions.20
for reaction control in organic synthesis.28 The zeolite-
catalyzed bromination of aromatics is highly selective
at low conversions, however, a decrease in selectivity
and reaction rate were observed with the progress of
the reaction.29 The main factor responsible for decreas-
ing the selectivity of the bromination was the effect of
HBr, which was liberated during the reaction, on the
structure of the zeolite catalyst.30 One way to increase
both the activity and the selectivity of the zeolite-cata-
lyzed bromination is to remove the HBr by using vari-
ous scavengers and oxidants such as inorganic
salts,31,32 organic bases, alcohols and carboxylic acids,33
oxiranes34 and oxygen.35 In this communication, we re-
portan efficientprocedure for ht e para-bromination of
halo- and alkyl-benzenes using a new brominating sys-
tem Br2/SO2Cl2, with the aid of microporous catalysts.
Numerous methods have also been proposed to increase
the yield and the selectivity of the para-bromo isomer,
which has greater commercial significance.21–27 In par-
ticular, zeolites have attracted much attention of organic
chemists over the last two decades. Due to their regular
microporous structure they proved to be useful as a tool
In the absence of catalyst, neat chlorobenzene (CB) was
very slowly monobrominated with Br2 with a molar
ratio of 2:1 at 25 °C and at100 °C, giving after 24 h,
CB conversions of ꢀ0.2% and ꢀ16%, respectively
(Table 1, runs 1 and 2). The rate and the isomer distri-
bution obtained in the bromination varied significantly
when the reaction was conducted in the presence of a
catalytic amount of Lewis acid catalysts, such as AlCl3
and FeCl3 (runs 3 and 4). The relatively high conver-
sions and selectivities were attributed to the effect of
polarizing the bromine molecule and consequently
enhancing its electrophilicity.1,2
Keywords: Bromination; Catalysis; Aromatics; Chlorobenzene;
Bromine; Sulfuryl chloride; Regioselectivity; Heterogeneous catalyst;
Zeolites; Clays; Cation-exchange.
*
Corresponding author. Tel./fax: +972 4 638 4650; e-mail: jallal_g@
zahav.net.il
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.04.116

4466
J. M. Gnaim, R. A. Sheldon / Tetrahedron Letters 46 (2005) 4465–4468
Table 1. Bromination of chlorobenzene (CB) with Br2 in the presence
of various catalystsa
Table 2. Bromination of CB with Br2/SO2Cl2 in the presence of
various catalystsa
Run Catalystb CB Conversion
Selectivity (mol %)
Run Catalyst
no.
CB Conversion
(mol %)
Selectivity (mol %)
no.
(mol %)
p-BCBb o-BCBb p/o Ratio
p-BCB o-BCB p/o Ratio
Co2+-X
Ni2+-Y
Mg2+-Y
Cu2+-Y
Co2+-Y
Ce3+-Y
Zn2+-Y
Cu2+-X
Ca2+-Y
63.0
63.0
68.1
73.6
82.8
86.0
86.5
88.7
89.2
89.1
93.0
94.2
93.8
92.8
96.9
92.7
93.1
96.7
10.9
7.0
5.8
6.2
7.2
3.1
7.3
6.9
3.3
8.2
13.3
16.2
15.1
12.9
31.3
12.7
13.5
29.3
1
None
None
AlCl3
Traces
15.6c
49.5
—
—
—
1
2
3
4
5
6
7
8
9
2
89.1
93.6
89.9
98.4
93.7
89.6
96.1
84.0
87.5
89.5
90.3
90.6
10.9
6.4
8.2
d
d
3
14.6
8.9
4
FeCl3
50.0
10.1
1.6
5
Zeolite X 13.5
61.5
14.9
8.6
6
LZ-Y82
Ca2+-Ye
Ce3+-Y
Fe3+-Y
Zn2+-Y
Ni2+-Y
Cu2+-Y
Cu2+-X
35.8
45.3
46.0
46.5
47.3
47.4
48.1
50.0
6.3
7
10.4
3.9
8
24.6
5.3
9
16.0
12.5
10.5
9.7
10
11
12
13
7.0
8.5
a See note 38 for conditions.
b See note 36.
9.3
9.6
9.4
a See note 35 for conditions.
Next we turned our attention to the bromination of CB
with SO2Cl2/Br2 in the presence of the cation-exchanged
zeolites X and Y. The results are shown in Table 2. The
observed reaction rates, CB conversions and para-selec-
tivities were substantially improved in comparison with
the corresponding values obtained using only Br2 under
the same conditions. With Ca2+-Y and Ce3+-Y catalysts,
ꢀ89% and ꢀ86% CB conversions, and ꢀ97% and ꢀ97%
para-selectivities were achieved, respectively (runs 6 and
9). These observations suggest that probably the mecha-
nism of the Br2/SO2Cl2-reaction is different from that of
the Br2-reaction. Despite the presence of SO2Cl2 in the
reaction mixture, no chlorination products were
observed.
b p-BCB: para-bromochlorobenzene; o-BCB: ortho-bromochloro-
benzene.
c The reaction was carried out at 100 °C.
d The amounts of AlCl3 and FeCl3 catalyst used were 0.7 and 0.8 g,
respectively.
e See note 36.
The combination of high Brønsted acidity and interla-
mellar spaces present in aluminosilicate structures make
them good candidates as chemo- and regio-selective cat-
alysts in electrophilic substitution of aromatics. There-
fore, we tested several types of microporous catalysts
such as SiO2, Al2O3, zeolite 3A, 4A, Y, mordenite, X,
LZ-Y82, KSF clay and K10 clay, in the bromination
of CB with Br2. The results show that CB conversions
and para-selectivities were improved compared to those
of the control reaction. For example, the large-pore size
zeolite X and zeolite LZ-Y82 catalyze the bromination
of CB with Br2, affording CB conversions of ꢀ14%
and ꢀ36%, and para-selectivities of ꢀ98% and ꢀ94%,
respectively (runs 5 and 6). These results also indicate
that larger-pore size zeolites are superior catalysts to
the smaller ones. This is probably due to the inability
of the reactants to diffuse through the channels of the
small-pore size zeolites and/or the small space available
in these structures may not be able to accommodate the
bulky transition state of the bromine-CB reaction.
In a continuous bromination experiment, a mixture of
CB, Br2 and SO2Cl2 with a 2:1:1 molar ratio was passed
through a glass column containing solid Ca2+-Y catalyst
at25 °C for a contact period of 2 h. The resulting reac-
tion mixture was analyzed and showed an ꢀ85% CB
conversion and a ꢀ96% para-selectivity. Interestingly,
by decreasing the amount of the Ca2+-Y catalyst 10-fold
under the same reaction conditions, the para-selectivity
of the bromination was almost unchanged, that is,
ꢀ97% and ꢀ96%, respectively. The [catalyst (g)/sub-
strate (mmol)] ratio in our present study (0.2 g catalyst
per 40 mmol substrate) is less than 0.005 g/ mmol, which
is lower than those (0.1–1.5 g/mmol) of previous
work.30,31,33,34,41
A large number of clays and zeolites supported with metal
cations such as Na+, K+, Cs+, Ca2+, Ba2+, Cu2+, Co2+
,
A typical reaction profile of the bromination of CB
using Br2/SO2Cl2 and Ca2+-Y zeolite indicates that the
para/ortho ratio is almost constant during the course
of the reaction. The effect of the calcination temperature
of the Ca2+-Y zeolite on the bromination of CB was also
examined. The optimum activity of the catalyst, which
corresponded with the maximum Brønsted acidity, was
obtained after calcination at about 400 °C. Preliminary
results showed that the Ca2+-Y zeolite catalyst, which
was regenerated by washing with deionized water, dry-
ing at110 °C and then reactivation at 400 °C, retained
its catalytic activity.
Ce3+, Al3+, Fe3+, Zn2+, Mg2+ and Ni2+, were prepared37
and their catalytic properties were examined in the bro-
mination of CB. The following observations can be made:
(1) greatimprovements of the CB conversions were ob-
served, for example by using Cu2+-X catalyst, a 50% CB
conversion was achieved at25 °C (run 13); (2) the cata-
lytic performance of the various partially cation-ex-
changed zeolites are strongly dependent on the type of
the zeolite and the charge and size of the cation used;
(3) the most active and para-selective of the cation-ex-
changed catalysts studied was Ce3+-Y, which afforded a
CB conversion of ꢀ46% and a para-selectivity of ꢀ96%,
that is a para/ortho ratio of ꢀ25 (run 8) and (4) the selec-
tivity of the bromination was higher at low conversions
and slightly decreased with the progress of the reaction.
The cation-exchanged reaction of Na+-Y with an aque-
ous solution of CaCl2 yielded the corresponding Ca2+-Y
zeolite (ꢀ3.6 mass% of Ca, which is ꢀ0.9 mmol of Ca in

J. M. Gnaim, R. A. Sheldon / Tetrahedron Letters 46 (2005) 4465–4468
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4468
J. M. Gnaim, R. A. Sheldon / Tetrahedron Letters 46 (2005) 4465–4468
35. Bromination of chlorobenzene with Br2: To a mixture of
chlorobenzene (11.3 g, 100 mmol) and the appropriate
solid catalyst (2.0 g) gently stirred in a 100 mL round
bottom flask, was added Br2 (20 mmol) at25 °C. The
mixture was stirred at rt for 24 h in a system protected
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NaHSO3 (25 mL) to neutralize excess Br2. The organic
layer was washed with water, separated and dried over
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solution was then drawn out and analyzed by GLC using a
Packard instrument Model 417, equipped with F.I.D.
coupled to an SP4290 integrator. The glass column (6 ft,
1.5 mm) was packed with 10% SP2401 on Supelcoport
100/120. The operating conditions were: detector temp
250 °C, injector temp 250 °C, carrier gas argon, oven temp
70 °C, ramp rate 5 °C/min, final temp 220 °C and sample
size 0.2 lL. Products were identified by comparing reten-
tion times with those of authentic samples. Nitrobenzene
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eluted in the following order: CB, nitrobenzene, p-BCB
and o-BCB.
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