Organic Process Research & Development 2000, 4, 30−33
Use of Sodium Bromate for Aromatic Bromination: Research and Development
Amiram Groweiss
TAMI (IMI) Institute for Research and DeVelopment, P.O.Box 10140, Haifa-Bay 26111, Israel
Abstract:
(vide infra) where neither mild reagents (like DBDMH or
NBS) nor Br gives satisfactory results.
Initial work on bromination with KBrO
Sodium bromate is a powerful brominating agent for aromatic
compounds that contain deactivating substituents. A bromina-
tion process, in which sodium bromate was utilized, was
optimized on laboratory scale. Addition of a strong acid into a
stirred aqueous solution, or slurry, of the substrate and bromate
salt at 40-100°C, leads to the decomposition of the bromate
ions and production of the active brominating species. Sub-
strates such as nitrobenzene, benzoic acid, and benzaldehyde
were brominated in high yields (85-98%) and specificity. The
reaction is especially useful for the bromination of disubstituted
benzenes, such as 4-nitrofluorobenzene or 4-fluorobenzoic acid.
Several substrates, such as dinitrobenzenes or nitrobenzoic
acids, did not undergo bromination at all. The main parameters
of the reaction and some of its synthetic potential are discussed.
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was carried out
2
by Harrison and co-workers, who prepared bromonitroben-
zene and also bromobenzoic and phthalic acids. In another
study Banerjee described the bromination of several other
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-6
substrates by the same method.
Thus far, the use of
NaBrO for such aromatic bromination has never been
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reported. Despite all of the similarities between the alkali
+
metals, there are several differences in action between Na
+
and K ions, and in many processes the use of the more
2 3
delicate KOH and K CO is preferred over the often sluggish
NaOH and Na CO . In bromination, however, our study has
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3
proven that sodium and potassium bromate act very similarly,
thus giving a commercial advantage to the less expensive
sodium salt.
The functionalization of aromatic compounds through
brominated intermediates is a very useful synthetic method.
Many reagents are used for the bromination step, including,
Results and Discussion
As shown in eq 1, sodium bromate was used to prepare
2
besides Br itself (with or without a catalyst), such com-
pounds as NBS, 1,3-dibromodimethylhydantoin (DBDMH),
benzyltrimethylammonium tribromide, etc. Most of these
agents are used for the bromination of aromatic substrates
that contain ring-activating groups, for example, toluene,
aniline, and phenol. Very few reagents can be used to
brominate compounds with strong electron-withdrawing
groups, such as nitrobenzene, benzoic acid, or benzene-
sulfonic acid. The lack of an efficient and economical method
for such bromination is probably one of the reasons meta-
substituted compounds are less common in many applications
than their ortho- or para-substituted isomers. This study deals
with meta bromination and recommends the utilization of
NaBrO for the bromination of aromatic substrates that
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contain one or two such deactivating groups.
Severe regulations on the use of sodium and potassium
bromate were imposed, in the past few years, by health and
environmental protection authorities. Some of their regular
brominated aromatic substrates with one- and two-electron
2
withdrawing groups (X ) NO , COOH, COOMe, CHO, F,
CF , etc.) (R ) H, F, Cl, etc.) in the meta position, in high
3
yields and good regioselectivities. The reactions were carried
out by mixing the substrate, a mineral acid (usually concen-
trated H SO ) and NaBrO . Since NaBrO and H SO are
2 4 3 3 2 4
not compatible, the brominations were performed by gradu-
ally adding one of the two reagents into the reaction mixture
(
a semi-batch process). In this instance there were three
possible modes of reaction:
a) Addition of concentrated H
of substrate and bromate in water.
b) Addition of solid NaBrO , in small portions, into a
solution of the substrate in aqueous H SO .
(
2 4
SO into a stirred slurry
(
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uses (like KBrO as a flour improver in baking processes)
1
were banned. In this atmosphere of diminishing markets and
declining demands, other uses are being sought. One such
potential utilization is in bromination and oxidation reactions.
Price-wise, however, none of the brominating reagents,
2
4
(
2) Harrison, J. J.; Pellegrini, J. P.; Selwitz, C. M J. Org. Chem. 1981, 46,
169-2171.
(3) Banerjee, A.; Banerjee, S.; Samaddar, H. J. Ind. Chem. Soc. 1979, 56, 985-
87.
2
9
2
including bromates, can compete with Br , and usually the
(
(
(
(
4) Banerjee, A.; Banerjee, S.; Samaddar, H. J. Ind. Chem. Soc. 1979, 56, 988-
price of KBrO is twice as much as that of bromine.
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990.
5) Banerjee, A.; Banerjee, G. C.; Dutt, S.; Banerjee, S.; Samaddar, H. J. Ind.
Chem. Soc. 1980, 57, 640-642.
6) Banerjee, A.; Banerjee, G. C.; Adak, M. M.; Banerjee, S.; Samaddar, H. J.
Ind. Chem. Soc. 1981, 58, 985-988.
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7) Two recent reports on bromination by NaBrO : (a) bromination of N,N-
Therefore, the use of bromate salts in processes may be
economically justified only when they provide substantial
advantages in the yield and reaction conditions over the use
2
of Br . The best example is the bromination of nitrobenzene
disubstituted benzamides: Dong, C.-H.; Julia, M.; Tang, J. Eur. J. Org.
Chem. 1998, 1689-1696. (b) Benzylic bromination of alkylbenzenes:
Kikuchi, D.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 1998, 63, 6023-6026.
(1) Chem. Ind. (London) 1989, 22, 734.
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Vol. 4, No. 1, 2000 / Organic Process Research & Development
10.1021/op9901947 CCC: $19.00 © 2000 American Chemical Society and The Royal Society of Chemistry
Published on Web 12/28/1999