An efficient and regioselective oxybromination of aromatic compounds using potassium bromide and oxone

Article abstract of DOI:10.1081/SCC-120006001

A simple, efficient and regioselective method for oxybromination of aromatics is reported. The electrophilic substitution of bromine generated in situ from potassium bromide using oxone as an oxidant for the first time.

Full text of DOI:10.1081/SCC-120006001

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AN EFFICIENT AND REGIOSELECTIVE OXYBROMINATION
OF AROMATIC COMPOUNDS USING POTASSIUM BROMIDE
AND OXONE®,*
N. Narender a , P. Srinivasu a , M. Ramakrishna Prasad a , S. J. Kulkarni b & K. V. Raghavan a
a Catalysis Group, Indian Institute of Chemical Technology, Hyderabad, 500007, India
b Catalysis Group, Indian Institute of Chemical Technology, Hyderabad, 500007, India
Published online: 16 Aug 2006.
To cite this article: N. Narender , P. Srinivasu , M. Ramakrishna Prasad , S. J. Kulkarni & K. V. Raghavan (2002) AN EFFICIENT
AND REGIOSELECTIVE OXYBROMINATION OF AROMATIC COMPOUNDS USING POTASSIUM BROMIDE AND OXONE®,*, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:15, 2313-2318, DOI:
10.1081/SCC-120006001
To link to this article: http://dx.doi.org/10.1081/SCC-120006001
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 15, pp. 2313–2318, 2002
AN EFFICIENT AND REGIOSELECTIVE
OXYBROMINATION OF AROMATIC
COMPOUNDS USING POTASSIUM
BROMIDE AND OXONEÕ
,
*
N. Narender, P. Srinivasu, M. Ramakrishna Prasad,
S. J. Kulkarni,y and K. V. Raghavan
Catalysis Group, Indian Institute of Chemical
Technology, Hyderabad-500007, India
ABSTRACT
A simple, efficient and regioselective method for oxybromina-
tion of aromatics is reported. The electrophilic substitution of
bromine generated in situ from potassium bromide using
oxoneÕ as an oxidant for the first time.
Halogenated aromatic compounds are a useful class of intermediates
as they are precursors to a number of organometallic species useful in the
synthesis of natural products and pharmaceutically important compounds.
The manufacture of a range of bulk and fine chemicals, including flame
retardants, disinfectants and antibacterial and antiviral drugs, involves
bromination.[1] Bromo aromatics are widely used as intermediates in the
manufacture of pharmaceuticals, agrochemicals and other specialty
*IICT Communication No. 4708
yCorresponding author. Fax: 0091-40-7173387/7173757;E-mail: sjkulkarni@iict.ap.
nic.in
2313
DOI: 10.1081/SCC-120006001
Copyright & 2002 by Marcel Dekker, Inc.
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2314
NARENDER ET AL.
chemical products. Consequently, a variety of methods for the bromination
of aromatics have been reported in the literature.[2–13]
Traditional methods of aromatic bromination involve the use of
non-selective hazardous acidic reagents such as mineral acids and metal
halides, which can lead to separation difficulties and unacceptable levels
of toxic and corrosive waste. Conventional bromination methods typically
use elemental bromine, a pollutant and a safety and health hazard. To
overcome these difficulties some researchers have utilized a combination
of hydrobromic acid and suitable oxidant such as tert-butylhydroperoxide
or hydrogen peroxide.[13–15] The replacement of such reagents by non-toxic
and more selective reagents is very desirable and represents an important
goal in the context of clean synthesis. We report a highly para selective
method for bromination of aromatic compounds based on the use of KBr
as a bromine source and oxoneÕ as an oxidant (Scheme 1).
Potassium peroxymonosulfate is an inexpensive and readily accessible
oxidizing agent. It is commonly used as oxoneÕ (2KHSO5ꢀKHSO4ꢀK2SO4)
and is a versatile oxidant for the transformation of a wide range of
functional groups.[16]
Scheme 1.
A number of different aromatic substrates were subjected to the
bromination reaction to test the generality of this method and the results
are summarized in Table 1. Efficient bromination of aromatic substrates
with good yields and regioselectivity observed with acetonitrile, methanol
as solvents (Table 1). As Table 1 shows that the reaction gives high
yields and para-selectivity for a range of substituted benzenes of high
activity. The results in Table 1 indicate that activated aromatic compounds
are more selective for nuclear bromination. Introduction of an electron-
withdrawing group on the aromatic ring substantially decreases the
rate of ring bromination (Table 1, Entry 8) while on electron donating
group increases it. These system yield selectively para brominated aromatics
unless the para-position (Table 1, Entry 7) is substituted. The para
substituted aromatics were brominated in the ortho-position. 2-Methoxy
naphthalene gives 1-bromo-2-methoxy naphthalene. When the less reactive
aromatics such as bromobenzene, nitrobenzene, benzoic acid failed to
undergo bromination under the same reaction conditions.

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OXYBROMINATION OF AROMATICS
2315
Table 1. Regioselective Oxybromination of Aromatic Compounds with KBr and
OxoneÕ
a
Yield (%)b
Time
(h)
Conversion
(%)
Entry
1.
Substrate
Solvent
Para
Ortho
Di-
CH3CN
MeOH
24
1
99
99
84
97
15
2
–
–
2.
CH3CN
MeOH
24
4
95
99
94
97
1
2
–
–
3.
4.
CH3CN
MeOH
24
4
99
99
–
–
99
99
–
–
CH3CN
MeOH
5
1
88
98
64
68
21
24
3
6
5.
6.
CH3CN
MeOH
8
1
99
100
70
78
15
12
14
10
CH3CN
MeOH
8
4
100
94
88
84
5
10
7
–
7.
CH3CN
MeOH
8
4
99
99
–
–
99
99
–
–
8.
9.
CH3CN
MeOH
24
24
64
91
63
86
1
5
–
–
CH3CN
MeOH
4
5
99
99
73
82
26
17
–
–
10.
11.
12
CH3CN
MeOH
24
24
< 5
< 5
< 5
< 5
–
–
–
–
CH3CN
MeOH
24
24
–
–
–
–
–
–
–
–
CH3CN
MeOH
–
–
–
–
–
–
–
–
–
–
aSubstrate (2 mmol), KBr (2.2 mmol), OxoneÕ (2.2 mmol), Solvent (10 mL), r.t.
bThe products were characterized by NMR, Mass and quantified by GC.

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2316
NARENDER ET AL.
A wide range of solvents have been employed in these reactions
including, carbon tetrachloride, hexane, dichloromethane, methanol and
acetonitrile. The best results were obtained when acetonitrile, methanol
were used as solvents compared to others (Table 2). The reaction is very
fast in methanol compared to acetonitrile.
We surveyed the oxybromination with various oxidants such as
oxoneÕ, tert-butylhydroperoxide, hydrogen peroxide and molecular O2.
Reactions were conducted with anisole as a probe-substrate at room
temperature in acetonitrile. However, oxoneÕ is far superior to the other
reagents. The role of oxoneÕ was confirmed by conducting a blank experi-
ment where the formation of bromo compound was not observed.
Oxybromination of an aromatic compound in the presence of oxoneÕ
proceeds according to the stoichiometry of Eq. (1). It is believed that
the bromination proceeds via the formation of hypobromous acid. The
hypobromous acid has higher instability due to pronounced ionic nature
and thus more reactivity towards the aromatic nucleus.
ArH þ KBr þ 2KHSO5ꢀKHSO4ꢀK2SO4 !
ArBr þ KOH þ K2S2O8ꢀKHSO4ꢀK2SO4þH2O
ð1Þ
2KHSO5 ꢀ KHSO4ꢀK2SO4 þ KBr !
HOBr þ KOH þ K2S2O8ꢀKHSO4ꢀK2SO4
ð2Þ
ð3Þ
_
_
2HOOSO3K ! 2OH þ 2OSO3K
_
_
KBrþ2HO þ 2OSO3K ! KOH þ HOBr þ K2S2O8
ArH þ HOBr ! ArBr þ H2O
ð4Þ
ð5Þ
Table 2. The Effect of Solvent on the Oxybromination of Anisole Using KCl –
OxoneÕ Systema
Yield (%)b
Time
(h)
Conversion
(%)
Entry
Solvent
Para
Ortho
Di-
1
2
3
4
5
Acetonitrile
Methanol
Dichloromethane
Hexane
Carbon tetrachloride
24
1
24
24
24
99
99
18
–
84
97
16
–
15
2
2
–
–
–
–
–
–
–
3
3
aAnisole (2 mmol), KBr (2.2 mmol), OxoneÕ (2.2 mmol), Solvent (10 mL), r.t.
bThe products were characterized by NMR, Mass and quantified by GC.

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OXYBROMINATION OF AROMATICS
2317
OxoneÕ, in direct comparison, has a higher onset of decomposition
than hydrogen peroxide and liberates less energy. This reaction is performed
at lower temperature, which provides a larger margin of safety. Additionally
oxoneÕ is a solid, allowing for the addition of precisely weighed amounts
of reagent to be used in the reaction.
In conclusion, we have developed a practical method using oxoneÕ
as an interesting alternative to hydrogen peroxide in the oxidative bromina-
tion of aromatic compounds. The commercial availability of the reagent,
simple reaction conditions, no evaluation of hydrogen bromide and
excellent yields of monobrominated products make our method valuable
from a preparative point of view.
General Procedure for the Bromination of Aromatic Compounds:
OxoneÕ (2.2 mmol) was added to a well stirred solution of KBr
(2.2 mmol) and substrate (2.0 mmol) in methanol (10 mL) and the reaction
mixture was allowed to stir at room temperature. The reaction was
monitored by thin layer chromatography (TLC). After the completion of
the reaction. The mixture was filtered and solvent evaporated under reduced
pressure. The products were purified by column chromatography over silica
1
gel and confirmed by H NMR and Mass spectra.
ACKNOWLEDGMENTS
We are thankful to Department of Science and Technology, New Delhi
for funding, DST Project No.: SP/S1/H07/97.
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2318
NARENDER ET AL.
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Received in the UK April 26, 2001