Simple catalyst-free regio- and chemoselective monobromination of aromatics using NBS in polyethylene glycol

Article abstract of DOI:10.1080/00397910801911752

NBS in polyethylene glycol has been efficiently utilized for regio- and chemoselective bromination of activated aromatics at room temperature to form the corresponding bromo products in excellent yields. Copyright Taylor & Francis Group, LLC.

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Simple Catalyst-Free
Regio- and Chemoselective
Monobromination of Aromatics
Using NBS in Polyethylene
Glycol
a
a
Katta Venkateswarlu , Kanaparthy Suneel
,
a
Biswanath Das , Kuravallapalli Nagabhushana
b
b
Reddy & Thummala Sreenivasulu Reddy
a
Organic Chemistry Division I, Indian Institute of
Chemical Technology, Hyderabad, India
b
Department of Chemistry, Sri Krishnadevaraya
University, Anantapur, India
Available online: 22 Dec 2008
To cite this article: Katta Venkateswarlu, Kanaparthy Suneel, Biswanath Das,
Kuravallapalli Nagabhushana Reddy & Thummala Sreenivasulu Reddy (2008): Simple
Catalyst-Free Regio- and Chemoselective Monobromination of Aromatics Using NBS in
Polyethylene Glycol, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 39:2, 215-219
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Synthetic Communications , 39: 215–219, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801911752
Simple Catalyst-Free Regio- and Chemoselective
Monobromination of Aromatics Using NBS in
Polyethylene Glycol
1
Katta Venkateswarlu, Kanaparthy Suneel, Biswanath Das,
1
1
2
Kuravallapalli Nagabhushana Reddy, and
2
Thummala Sreenivasulu Reddy
1
Organic Chemistry Division I, Indian Institute of Chemical Technology,
Hyderabad, India
Department of Chemistry, Sri Krishnadevaraya University, Anantapur, India
2
Abstract: NBS in polyethylene glycol has been efficiently utilized for regio- and
chemoselective bromination of activated aromatics at room temperature to form
the corresponding bromo products in excellent yields.
Keywords: Aromatic bromination, catalyst-free, ecofriendly reaction conditions,
PEG-400, regio- and chemoselectivity
The bromination of aromatic compounds is an important reaction in
[1]
synthetic organic chemistry. Bromoarenes are utilized as pharmaceuticals,
[
2]
agrochemicals, specialty chemicals, and flame retardants. Various aryl-
bromides possess significant antioxidant, antibacterial, and antitumor
[3]
properties. They can also undergo C-C bond formation via transmetala-
[
4]
tion reactions such as Heck, Stille, and Suzuki reactions. The direct bro-
mination of aromatic compounds using bromine generates toxic and
corrosive HBr and usually forms the mixture of mono-and polybrominated
[
5]
products. Consequently various other brominating agents have been
[
6]
developed. However, because of ease of handling and availability, NBS
is generally utilized for bromination of aromatic compounds. Earlier
Received December 27, 2007.
Part 125 in the series ‘‘Studies on Novel Synthetic Methodologies.’’
Address correspondence to Biswanath Das, Organic Chemistry Division I,
Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007,
Andra Pradesh, India. E-mail: biswanathdas@yahoo.com
2
15

216
K. Venkateswarlu et al.
Scheme 1.
[
6b,d,e,h]
methods involving the applications of NBS
are associated with
certain disadvantages such as long reaction times, high temperatures, poor
selectivity, unsatisfactory yields, and complex experimental procedures.
[7]
In connection with our work on the development of useful syn-
thetic methodologies, we have discovered that bromination of activated
aromatics can efficiently be accomplished with NBS at room temperature
using PEG-400 as the reaction medium (Scheme 1).
The method has been applied for the preparation of a series of bro-
minated phenols, anilines, and their derivatives (Table 1). The corre-
sponding monobrominated products were formed in excellent yields.
Most of the anilines and phenols underwent the conversion rapidly.
4
-Nitroaniline (entry e) afforded the desired product in 20 min with a
yield of 91%. Previously, it was difficult to brominate this compound.
Different functionalities such as alkyl, halogen, nitro, and carbonyl
groups remained unaffected.
The present conversion furnished only the monobrominated pro-
ducts, and the conversion is highly regio-and chemoselective. Phenols
and anilines formed the corresponding para-bromo compounds as the
sole products. However, when the para-position of a substrate was
blocked with a substituent, ortho-product was yielded. The method is
associated with only nuclear bromination of the activated arynes, but
the benzylic alkyl groups or the acyl groups (entries b, c, j, o, p, u,
and x) were not brominated.
The method is also effective for monobromination of heterocyclic
aromatic compounds. Thus amino pyridines (entries l and m) formed
the desired brominated products in high yields. Several coumarin deriva-
tives (entries t–w) also underwent the bromination smoothly to produce
the corresponding 3-bromocoumarins.
[8]
Polyethylene glycol (PEG-400) has been utilized in the present con-
version as an efficient reaction medium. It is an inexpensive biologically
acceptable polymer. However, its application in organic synthesis has
not yet been fully explored. The role of PEG is probably to polarize
the >N-Br bond to provide nuclear bromination of aromatics.
In conclusion, we have developed a mild and efficient method for bro-
mination of activated aromatics by treatment with NBS using PEG as the

Monobromination of Aromatics Using NBS
217
a
Table 1. Monobromination of aromatic compounds with NBS in PEG-400
Substrate
(1)
Time
(min)
Product
(2)
Isolated
yield (%)
Entry
a
b
c
d
e
f
g
h
i
Aniline
p-Toluidine
o-Toluidine
4-Chloroaniline
4-Nitroaniline
2-Nitroaniline
N,N-Dimethyl-aniline
2-Napthylamine
2-Aminobenzo-phenone
4-Aminoaceto-phenone
4-N,N-dimethylamino-
benzaldehyde
10 4-Bromoaniline
5
98
99
94
99
91
89
98
99
80
97
98
2-Bromo-p-toluidine
10 4-Bromo-o-toluidine
2-Bromo-4-chloroaniline
1
20 2-Bromo-4-nitroaniline
25 4-Bromo-2-nitroaniline
1
2
4-Bromo-N,N-dimethylaniline
1-Bromo-2-napthylamine
25 2-Amino-5-bromobenzophenone
j
k
5
1
4-Amino-3-bromoacetophenone
3-Bromo-4-N,N-dimethyl-
aminobenzaldehyde
l
2-Aminopyridine
DMAP
Phenol
p-Cresol
o-Cresol
Salicylaldehyde
Vanillin
2-Napthol
7-Hydroxy-coumarin
7-Benzyloxy-coumarin
7-Hydroxy-4-
5
5-Bromo-2-aminopyridine
96
86
98
97
94
91
87
99
92
95
89
m
n
o
p
q
r
s
t
u
v
15 3-Bromo-DMAP
15 4-Bromophenol
5
5
25 5-Bromosalicylaldehyde
30 5-Bromovanillin
2
120 3-Bromo-7-hydroxycoumarin
120 3-Bromo-7-benzyloxycoumarin
150 3-Bromo-7-hydroxy-
4-methyl-coumarin
150 3-Bromo-4-hydroxycoumarin
180 No reaction
2-Bromo-p-cresol
4-Bromo-o-cresol
1-Bromo-2-napthol
methyl-coumarin
4-Hydroxy-coumarin
4,6-Dimethyl-coumarin
w
x
90
—
a
1
13
The structures of the products were established from the spectral ( H and
NMR and MS) data.
C
reaction medium. The simple experimental procedure, catalyst-free
conversion, short reaction times, high yields of the monobrominated
products, and impressive regio-and chemoselectivity are notable advan-
tages of the present method. The method is expected to be of great syn-
thetic utility.
EXPERIMENTAL
General
To a suspension of activated aromatic (1 mmol) in PEG-400 (2 g), NBS
(
1.05 mmol) was added slowly, and the mixture was stirred at room

218
K. Venkateswarlu et al.
temperature. The reaction was monitored by thin-layer chromotography
TLC). After completion, the mixture was poured onto water (10 ml) and
(
extracted with EtOAc (3 ꢀ 10 ml). The combined extract was concen-
trated, and the residue was subjected to column chromatography (silica
gel, hexane–EtOAc) to obtain pure monobrominated product. The spec-
1
13
tral ( H and C NMR and MS) data of some representative products
are given next.
Data
1
Compound 2m: H NMR (200 MHz, CDCl þ d -DMSO): d 8.41 (1 H, s),
3
6
1
3
8
.21 (1 H, d, J ¼ 6.0 Hz), 6.79 (1 H, d, J ¼ 6.0 Hz), 2.96 (6 H, s);
C
NMR (50 MHz, CDCl þ d -DMSO): d 156.7, 152.9, 148.4, 113.5,
3
6
þ.
1
12.0, 42.2; EIMS: m=z 202, 200 (M ).
1
Compound 2s: H NMR (200 MHz, CDCl ): d 7.97 (1 H, d,
3
J ¼ 8.3 Hz), 7.70 (1 H, d, J ¼ 9.1 Hz), 7.67 (1 H, d, J ¼ 9.1 Hz), 7.50
1
3
(
1 H, m), 7.33 (1 H, m), 7.21 (1 H, d, J ¼ 8.9 Hz), 5.83 (1 H, brs);
C
NMR (50 MHz, CDCl ): d 150.5, 132.2, 129.6, 129.2, 128.1, 127.8,
3
þ.
1
25.2, 124.1, 117.1, 106.1; EIMS: m=z 224, 222 (M ).
1
Compound 2u: H NMR (200 MHz, CDCl ): d 7.99 (1 H, s), 7.48–
3
1
.30 (6 H, m), 6.98–6.84 (2 H, m), 5.06 (2 H, s); C NMR (50 MHz,
3
7
CDCl ): d 162.0, 157.3, 154.9, 144.3, 135.4, 128.7, 128.4, 128.2, 127.3,
3
þ.
1
13.7, 101.8, 70.6; EIMS: m=z 332, 330 (M ).
1
Compound 2v: H NMR (200 MHz, CDCl þ d -DMSO): d 10.21
3
6
(
2
1 H, brs), 7.48 (1 H, dd, J ¼ 8.0, 2.0 Hz), 6.78 (1 H, dd, J ¼ 8.0,
1
3
.0 Hz), 6.75 (1 H, d, J ¼ 2.0 Hz), 2.58 (3 H, s); C NMR (50 MHz,
CDCl þ d -DMSO): d 161.8, 156.7, 153.2, 150.8, 125.6, 114.2, 112.3,
3 6
þ
07.5, 102.2, 19.4; EIMS: m=z 256, 254 (M ).
1
ACKNOWLEDGMENTS
The authors thank CSIR and UGC, New Delhi, for financial assistance.
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