Secondary sonochemical effect on Mo-catalyzed bromination of aromatic compounds

Article abstract of DOI:10.1016/j.ultsonch.2010.11.006

The Molybdate-catalyzed bromination of various aromatic compounds in the presence of KBr/H₂O₂ in an aqueous/chloroform biphasic system occurred under ultrasonic irradiation, whereas the reaction did not take place under conventional mechanical stirring (1400 rpm). The sonochemical activation was found to be of secondary effect, attributed to lowering pH by sonolysis of CHCl₃-H₂O solvents mixture.

Full text of DOI:10.1016/j.ultsonch.2010.11.006

Ultrasonics Sonochemistry 18 (2011) 753–756
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Secondary sonochemical effect on Mo-catalyzed bromination
of aromatic compounds
Jean-Marc Lévêque a,b, Mitsue Fujita b, Alexis Bosson a, Hajime Sohmiya b, Christian Pétrier c,
Naoki Komatsu b, Takahide Kimura b,
⇑
a Laboratoire de Chimie Moléculaire et Environnement, ESIGEC, Université de Savoie, 73376 Le Bourget du Lac cedex, France
b Department of Chemistry, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan
c LEPMI, 1130 rue de la Pisicne 38402 Saint Martin d’Hères cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 May 2010
Received in revised form 8 November 2010
Accepted 9 November 2010
Available online 17 November 2010
The Molybdate-catalyzed bromination of various aromatic compounds in the presence of KBr/H2O2 in an
aqueous/chloroform biphasic system occurred under ultrasonic irradiation, whereas the reaction did not
take place under conventional mechanical stirring (1400 rpm). The sonochemical activation was found to
be of secondary effect, attributed to lowering pH by sonolysis of CHCl3–H2O solvents mixture.
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
Bromination
Secondary sonochemical effect
Molybdate
Hydrogen peroxide
Chloroform
Sonolysis
1. Introduction
efficiency leading subsequently to the production of large amounts
of toxic wastes. More recently, Singhal et al. developed an interest-
Halogenated aromatic compounds are a useful class of interme-
diates in synthetic organic chemistry. In particular, brominated
aromatic compounds are widely used in the manufacture of several
special chemical products among antibacterials, disinfectants,
pharmaceuticals, agrochemicals [1]. In addition, they also play an
important role in the design of metal catalyzed coupling reactions
[2]. Various synthetic routes have thus been reported in the litera-
ture through the last century. The most commonly used reagent re-
mains molecular bromine associated to various acidic co-catalysts
such as Lewis acids or zeolites [3]. Nevertheless, all of them exhibit
also several major drawbacks such as toxicity, corrosion, hazard
and pollutant to the environment. In the nowadays necessity of
developing sustainable organic synthetic routes, efforts were fo-
cused on the development of greener methods under milder condi-
tions to afford bromoarenes. Therefore, in the recent years, several
methodologies involving milder brominating reagents, among
N-bromosuccinimide (NBS) [4], NBS/Brönsted acids (H2SO4,
CF3COOH, PTSA, etc.) [5], NBS/SiO2 [6], HBr/DMSO [7], KBrO3 [8]
or KBr/H2O2/Oxone [9] were developed. Nevertheless, these meth-
odologies still suffer major drawbacks such as hazard and toxicity
of the prepared reagents, use of organic solvents and poor atom
ing alternative route by using a solid organic ammonium tribro-
mide, the N-methylpyrrolidin-2-one hydrotribromide (MPHT) as
a brominating agent in the presence of 30% hydrogen peroxide at
room temperature in methanol [10]. Various bromoarenes were
afforded in excellent yields in very short times but the use of meth-
anol, the nature and the used amount of the catalyst may postpone
a further development.
In the late 90s, Conte et al. reported an interesting catalytic
method of bromination of aromatic compounds by KBr, H2O2,
and Na2MoO4 envisaged in a manner similar to the bio-halogena-
tion performed by haloperoxidase enzymes [11,12]. This bromina-
tion is based on bromide salt oxidation to bromonium- or
hypobromite-like species (‘‘Br+’’) by hydrogen peroxide. The reac-
tion system is Br-atom efficient because of the use of bromide
Br- for the bromination, in contrast to the bromination by bromine
Br2 which utilizes only 50% of the available halogen with the other
half forming HBr waste [13]. The proposed mechanism is com-
posed of reaction steps involving a consumption of H2O2 and a cat-
alytic use of Mo-complex enabling the formation of the ‘‘Br+’’
moieties (BrOH, Br2, Br3À) in a H2O/CHCl3 biphasic medium
[11,14], which is illustrated in Scheme 1.
Even if the concept, in terms of Green Chemistry goals, remains
attractive the reaction under vigorous stirring (1000 rpm) affords
only low to moderate yields (56–65%) in 4 h. Moreover, up to
⇑
Corresponding author. Tel.: +81 77 548 2108; fax: +81 77 548 2405.
E-mail address: kimura@belle.shiga-med.ac.jp (T. Kimura).
1350-4177/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2010.11.006

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J.-M. Lévêque et al. / Ultrasonics Sonochemistry 18 (2011) 753–756
tion, the low-yield of H2O2 was not enough to carry out the reac-
tion. Thus, H2O2 had to be added.
In order to elucidate the mechanism of the ultrasonic activation,
it was firstly confirmed that molybdate was doubtless involved in
the reaction mechanism [11]. In its absence only 10% of bromophe-
nol at 36.6 kHz and 16% at 480 kHz were obtained as shown in
Table 2.
That is, the uncatalyzed bromination with BrÀ and H2O2 under
our experimental conditions does not work out. In our study,
5 mol% of molybdate gave the best results. Also, the selectivity of
o- and p- isomers in the reaction in the absence of molybdate
was slightly different from those in the presence of molybdate.
The H2O/CHCl3 ratio of the solvents system also affected sensibly
the yield as shown in Table 3. Moreover, in the absence of CHCl3,
the reaction did not proceed at all. Although the biphasic condi-
tions are important, the solvent ratio does not affect significantly
the yield.
Our initial hypothesis was that ultrasound may accelerate the
decomposition of the ‘‘peroxomolybdate-hypobromite’’ intermedi-
ate to accelerate cycling of the catalyst. According to the best of our
knowledge, there is yet no report on the sono-activation of homo-
geneous catalysis, although there are many reports on the sono-
activation of solid catalysis and on sonolysis of materials [17]. If
it is so in our case, the fact must be very interesting.
Additionally, the difference of the initial pHs between Conte’s
reaction and ours, respectively 1.1 and 4.6, incited us to investigate
further in this direction. Several experiments under both mechan-
ical stirring and ultrasonic irradiation were carried out at the same
pH, Table 4.
As shown in Table 4, the reaction under mechanical stirring did
not occur without adjusting pH prior to the reaction. By lowering
the initial pH of 4.6 to 1.3 by addition of HClO4, the reaction affor-
ded 44% of bromophenol in 1 h under stirring conditions empha-
sizing that the acidic conditions are required in this reaction
system [11,13].
Scheme 1. Plausible mechanism for the molybdate-catalyzed bromination of
aromatic compounds.
50 mol% of catalyst Na2MoO4 and additional H2O2 are necessary.
Ultrasonic irradiation was thus expected to improve this bromina-
tion reaction through the synergism of its both chemical and phys-
ical effects, since ultrasound on the one hand produces H2O2 via
the sonolysis of water and on the second enhances heterogeneous
reactions [15].
2. Experimental
In a flat bottom reaction flask, 0.1 mmol of substrate, 0.1 mmol
of H2O2, 0.126 mmol of KBr, and 0.005 mmol of (NH4)6Mo7O24
were mixed in a 5 mL H2O/1 mL CHCl3 solvent. Then the solution
was submitted to ultrasound in a 36.6 or 480 kHz thermo-con-
trolled ultrasonic bath at 0.2 W/mL acoustic intensity [16] for 1
or 2 h at 20 °C. Runs under conventional mechanical stirring at
1400 rpm were also carried out for comparison. Organic materials
were separated into CHCl3 phase and analyzed by GC using the
internal standard method.
Thus, these results led us to envisage that the ultrasonic activa-
tion does come perhaps not from the decomposition of the homo-
geneous catalyst but from the homolytic decomposition of
3. Results and discussion
Results obtained under both conventional and non conventional
activation methods are summarized in Table 1.
Table 2
In 2 h under stirring conditions, the bromination of phenol did
not occur at all, whereas under ultrasonic conditions, bromophenol
was obtained at 71% and 81% yield at, respectively 36.6 and
480 kHz. Anisole and acetanilide were also brominated efficiently
in 4 h under sonication. Ultrasound is decisive to initiate the reac-
tion, but the difference of frequencies of ultrasound irradiated
doesn’t make a large difference. When the reaction was carried
out with no addition of H2O2, yields were low at both frequencies.
Although the sono-production of H2O2 was expected under sonica-
a
Bromination of phenol with various amounts of catalyst (NH4)6Mo7O24
.
Yield of bromophenol %b (o: p ratio)
(NH4)6Mo7O24(mol%)c
Frequency (kHz)
50
10
5
0
36.6
480
59 (26:74)
57 (25:75)
79 (26:74)
75 (25:75)
87 (25:75)
78 (25:75)
10 (39:61)
16 (35:65)
a
Phenol 0.1 mmol, H2O2 0.1 mmol, KBr 0.126 mmol. Solvent: CHCl3 5 mL + H2O
5 mL, Time: 2 h, Temp.: 20 °C.
b
Determined by GC (internal standard: dodecane).
mol% to phenol.
c
Table 1
Bromination of aromatic substrates with H2O2 and KBr, catalyzed by (NH4)6Mo7O24 in
a two phase systema.
Substrate
Time (h)
Yield %b (o: p ratio)
Table 3
a
Stirring
U.S.
U.S.
Dependency of bromination of phenol on the solvent ratio H2O/CHCl3
.
(1400 rpm)
(36.6 kHz)
(480 kHz)
Yield of bromophenol %b (o: p ratio)
H2O (mL)/CHCl3 (mL)
2
2
4
0
–
0
71 (26:74)
17 (32:68)c
96 (4:96)
81 (27:73)
15 (33:67)c
75 (4:96)
OH
Frequency (kHz) 5.0/5.0
5.0/2.0
5.0/1.0
5.0/0.5
5.0/0.0
OCH3
36.6
480
87 (25:75) 77 (24:76) 71 (26:74)c 58 (26:74)d
78 (25:75) 76 (25:75) 81 (27:73) 70 (27:73)
0
0
4
0
92 (0:100)
100 (0:100)
NHCOCH3
a
Phenol 0.1 mmol, H2O2 0.1 mmol, KBr 0.126 mmol, (NH4)6Mo7O24 0.005 mmol,
a
Substrate 0.1 mmol, H2O2 0.1 mmol, KBr 0.126 mmol, (NH4)6Mo7O24
Time: 2 h, Temp.: 20 °C.
b
0.005 mmol, Solvent: CHCl3 1 mL + H2O 5 mL, Temp.: 20 °C.
Determined by GC (internal standard: dodecane).
7.5% of dibromophenol was detected.
b
c
Determined by GC (internal standard: dodecane).
Without H2O2.
c
d
15% of dibromophenol was detected.

J.-M. Lévêque et al. / Ultrasonics Sonochemistry 18 (2011) 753–756
755
Table 4
Table 5
Effect of the initial pH on the bromination of phenola.
pH changea and bromination of phenolb in various solvent system.
Yield of bromophenol %b (o: p ratio)
Solvent system
pHa
Phenolc
Bromophenold (o: p ratio)
pH 4.6c
pH 1.3d
CH2Cl2/H2O
CHCl3/H2O
CCl4/H2O
2.17
1.24
1.36
61
3
0
22 (26:74)
81 (27:73)
2.2 (0:100)e
Stirring (1400 rpm)
U. S. (480 kHz)
0
44 (24: 76)
68 (24:76)
48 (24:76)
a
A
mixture of chlorinated methane 5 mL and H2O 5 mL was sonicated at
a
Phenol 0.1 mmol, H2O2 0.1 mmol, KBr 0.126 mmol, (NH4)6Mo7O24 0.005 mmol,
Solvent: H2O 5 mL + CHCl3 1 mL, Time: 1 h, Temp.: 20 °C.
480 kHz, 20 °C for 1 h.
A mixture of phenol 0.1 mmol, H2O2 0.1 mmol, KBr 0.126 mmol, (NH4)6Mo7O24
0.005 mmol in H2O 5 mL + chlorinated methane 1 mL was sonicated at 480 kHz,
b
b
Determined by GC (internal standard: dodecane).
c
An initial pH without HClO4.
20 °C for 1 h.
d
An initial pH with 0.37 mmol of HClO4.
c
Recovered phenol.
Determined by GC (internal standard: dodecane).
14 % of dibromophenol was detected.
d
e
As the reaction smoothly takes place at pH below two [13], one
of the main reason of the acceleration of the reaction under ultra-
sound might be the lowering of pH by homolytic cleavage of CHCl3.
When CCl4 was used instead of CHCl3, a little amount of bromo-
phenol was obtained although all phenol was consumed as shown
in Table 5. It may be because in aqueous solution of CCl4 phenol
and halogenated phenol are easily degraded by sonication [23].
On the other hand, CH2Cl2 did not work well, since the vapor
pressure of CH2Cl2 is too high to sonolyze solvents as shown here
below, Table 5.
Scheme 2. Radical decomposition of chloroform under ultrasonic irradiation.
Thus, the activation mechanism of the Mo-catalyzed bromina-
tion by ultrasound can be attributed to the secondary indirect
sonochemical effect, that is the lowering of pH by sonolysis of
CHCl3–H2O solvents. A strategic use of the secondary sonochemical
effect such as in situ lowering pH by sonolysis should be taken into
account in the application of ultrasound. However, the acceleration
of the cycling of the catalyst by the sonolysis of the ‘‘peroxomolyb-
date-hypobromite’’ intermediate cannot be ruled out yet. Work is
under progress to clarify this point.
Acknowledgement
This work was supported by Grants-in-Aid for Scientific Re-
search No. 21560792 from the Ministry of Education, Culture,
Sports, Science and Technology.
Fig. 1. pH change of various mixtures by 480 kHz sonication at 20 °C. (NH4)6Mo7O24
0.005 mmol, Ph OH 0.1 mmol, KBr 0.126 mmol, H2O2 0.1 mmol, CHCl3 1 mL, H2O
5 mL.
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