Oxidative bromination of aromatic compounds using O-iodoxybenzoic acid with tetraethylammonium bromide

Article abstract of DOI:10.1080/00397910801914103

A mild and selective procedure for the bromination of activated arenes using o-iodoxybenzoic acid and tetraethylammonium bromide is presented. The reactions were carried out at room temperature and gave moderate to excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910801914103

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Oxidative Bromination of
Aromatic Compounds Using
O-Iodoxybenzoic Acid with
Tetraethylammonium Bromide
Dinesh S. Bhalerao a , Ulhas S. Mahajan a &
Krishnacharya G. Akamanchi a
a Department of Pharmaceutical Sciences and
Technology, Institute of Chemical Technology,
Mumbai, India
Published online: 25 Aug 2010.
To cite this article: Dinesh S. Bhalerao , Ulhas S. Mahajan & Krishnacharya G.
Akamanchi (2008): Oxidative Bromination of Aromatic Compounds Using O-
Iodoxybenzoic Acid with Tetraethylammonium Bromide, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
38:16, 2814-2819
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Synthetic Communications1, 38: 2814–2819, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801914103
Oxidative Bromination of Aromatic Compounds
Using O-Iodoxybenzoic Acid with
Tetraethylammonium Bromide
Dinesh S. Bhalerao, Ulhas S. Mahajan, and
Krishnacharya G. Akamanchi
Department of Pharmaceutical Sciences and Technology, Institute of Chemical
Technology, Mumbai, India
Abstract: A mild and selective procedure for the bromination of activated arenes
using o-iodoxybenzoic acid and tetraethylammonium bromide is presented. The reac-
tions were carried out at room temperature and gave moderate to excellent yields.
Keywords: Bromoarenes, o-iodoxybenzoic acid, oxidative bromination, tetra-
ethylammonium bromide
Aryl halides are important synthetic intermediates for a variety of transfor-
mations including carbon–carbon bond formation via cross-coupling reac-
tions such as Stille–Suzuki, Heck, and Sonogashira and carbon–heteroatom
bond formation via aromatic functionalization protocols.[1] The traditional
method for aromatic bromination is electrophilic substitution with molecu-
lar bromine.[2] However, despite the widespread use of molecular bromine
as an electrophilic reagent, it is a toxic, difficult to handle, low-boiling
lachrymatory liquid that causes severe burns on contact with skin.[3] Other
reagents used for aromatic brominations are N-halo succinamides,
HBr=TBHP (t-butylhydroperoxide) or H2O2, quaternaryammonium
tribromide, PHP (pyridinium hydrobromide perbromide), KBr=NaBO3,
NaBr=NaClO2=Mn(acac)3=moist montmorillonite, LiBr=CAN (ceric
ammoniumnitrate), BuOBr=zeolite, benzyltriphenylphosphonium tribro-
mide, NaBr=dimethyl dioxirane,[4] and bromodimethylsulfonium bromide
Received December 1, 2007
Address correspondence to Krishnacharya G. Akamanchi, Department of
Pharmaceutical Sciences and Technology, Institute of Chemical Technology,
Matunga, Mumbai 400019, India. E-mail: kgap@rediffmail.com
2814

Bromination of Aromatic Compounds
2815
Scheme 1.
(BDMS).[5] Recently, using bromine–dioxane complex under solvent-free
conditions, hypervalent iodine reagents[6] such as polymer-supported
o-iodoxybenzoic acid (IBX) amide with TEAB and PhI(OAc)2 with KBr
have been used for aromatic bromination. Despite the many halogenation
methods that are available, additional methods for this transformation are
still valuable.
Hypervalent iodine reagents have found widespread applications in
organic synthesis because of their selectivity and simplicity in use. Our
group has been extensively working on the development of novel
methodologies using hypervalent iodine reagents,[7] mainly IBX and
Dess–Martin periodinane (DMP). In continuation of our studies on the
development of newer applications of hypervalent iodine (k5) compounds,
herein we report the application of IBX with TEAB for oxidative bromin-
ation of aromatic compounds under neutral conditions (Scheme 1).
The method is simple and selective, giving good to excellent yields of
brominated products. A series of arenes was selected for attempted bromin-
ation. Stoichiometric combination of IBX with TEAB in acetonitrile
smoothly brominated a variety of substrates at room temperature
(Table 1). Inspection of the results gathered in Table 1 reveals that this
combination of reagents is effective for the monobromination of elec-
tron-rich aromatics (entries 1–10) and thiophene (entry 11). Additionally,
this combination of reagents is capable for the transformation of an
N,N-diallylbenzenamine into the corresponding N,N-diallyl-4-bromo-
benzenamine while the alkene group remained unaffected, showing the
chemoselectivity of the method (entry 2). When the reaction was
performed on N-benzyl-N-methylbenzenamine, bromination occured at
the para position of aniline (entry 3). When phenol and aniline were sub-
jected to the reaction conditions, it led to a complex mixture (entries 12
and 13). The substrates containing electron-withdrawing groups such as
nitro, ester, and nitrile did not react, indicating the need of electron-
donating groups (entries 14–16).
Among the pentavalent iodine reagents, DMP was also studied for
this transformation. IBX was found to be the most effective in terms of
conversions and reaction rates.
In summary, a simple, chemoselective, and mild method has been
developed for oxidative bromination of aromatic compounds by using
a combination of IBX with TEAB.

2816
D. S. Bhalerao, U. S. Mahajan, and K. G. Akamanchi
Table 1. Aromatic bromination using IBX with TEABa
Time yield
(min) (%)b
Entry
1
Substrate
Product
Mp
10
96 54–55 ꢀC[4b]
2
10
96
Oil[9]
3
4
10
10
96
95
Oil[10]
Oil[10]
5
6
600
300
85
92
Oil[4b]
Oil[6a]
(Continued)

Bromination of Aromatic Compounds
2817
Table 1. Continued
Time yield
(min) (%)b
Entry
7
Substrate
Product
Mp
720
80 80–82 ꢀC[4b]
8
9
300
92
90
65–67 ꢀC[5]
300
Oil[5]
10
60
94
Oil[11]
11
12
180
5
92
—
Oil[8]
Complex mixture
—
(Continued)

2818
D. S. Bhalerao, U. S. Mahajan, and K. G. Akamanchi
Table 1. Continued
Time yield
(min) (%)b
Entry
13
Substrate
Product
Mp
—
Complex mixture
5
—
14
15
16
NR
NR
NR
—
—
—
—
—
—
—
—
—
aReactions were performed on a 5 mmol scale using 1.1 equiv. of IBX with
TEAB. Reactions were monitored by TLC and GC analysis on 5% OV-17 (60,
1=800) column and FID detector.
bIsolated yields.
EXPERIMENTAL
General Experimental Procedure for Aromatic Bromination
To a stirred suspension of IBX (1.54 g, 5.5 mmol) in CH3CN (20 ml),
TEAB (1.16 g, 5.5 mmol) was added. A yellow suspension was observed
to which substrate (5 mmol) was added in one portion after 5 min. The
reaction mixture was stirred at room temperature until complete con-
sumption of starting material was observed by thin-layer chromato-
graphy (TLC). Acetonitrile was removed under reduced pressure, and
the resultant residue was washed with ethyl acetate (25 ml) followed by
10% sodium bisulfite solution (25 ml), saturated sodium carbonate
(25 ml), and brine (25 ml). The organic layer was dried over anhydrous
sodium sulfate and concentrated under reduced pressure to give the crude

Bromination of Aromatic Compounds
2819
product. The pure product was isolated after column chromatography
(silica-gel mesh size 60–120, eluent n-hexane).
ACKNOWLEDGMENT
Authors thank the University Grants Commission (UGC), India, for
financial support.
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