Regioselective photochemical and microwave mediated monobromination of aromatic compounds using 2,4,4,6-tetrabromo-2,5-cyclohexadienone

Article abstract of DOI:10.1080/00397910701519119

Bromination of different aromatic substrates have been described using 2,4,4,6-tetrabromo-2,5-cyclohexadienone in conjunction with microwave and ultraviolet radiations. Important features of the work include high regioselectivity obtained in very short to moderate reaction time, atom economy, and recyclability of the reagent. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701519119

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Regioselective Photochemical and
Microwave Mediated Monobromination
of Aromatic Compounds using
2,4,4,6–Tetrabromo‐2,5‐cyclohexadienone
Neeraj Gupta a , Goverdhan L. Kad a , Vasundhara Singh b & Jasvinder Singh
a
a Department of Chemistry, Centre for Advanced Studies in Chemistry,
Punjab University, Chandigarh, India
b Department of Applied Sciences, Punjab Engneering College, (Deemed
University), Chandigarh, India
Published online: 05 Oct 2007.
To cite this article: Neeraj Gupta , Goverdhan L. Kad , Vasundhara Singh & Jasvinder Singh (2007):
Regioselective Photochemical and Microwave Mediated Monobromination of Aromatic Compounds using
2,4,4,6–Tetrabromo‐2,5‐cyclohexadienone, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:19, 3421-3428
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Synthetic Communicationsw, 37: 3421–3428, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701519119
Regioselective Photochemical
and Microwave Mediated
Monobromination of Aromatic Compounds
using 2,4,4,6–Tetrabromo-2,5-
cyclohexadienone
Neeraj Gupta and Goverdhan L. Kad
Department of Chemistry and Centre for Advanced Studies in Chemistry,
Punjab University, Chandigarh, India
Vasundhara Singh
Department of Applied Sciences, Punjab Engneering College, (Deemed
University), Chandigarh, India
Jasvinder Singh
Department of Chemistry and Centre for Advanced Studies in Chemistry,
Punjab University, Chandigarh, India
Abstract: Bromination of different aromatic substrates have been described using
2,4,4,6-tetrabromo-2,5-cyclohexadienone in conjunction with microwave and ultra-
violet radiations. Important features of the work include high regioselectivity
obtained in very short to moderate reaction time, atom economy, and recyclability
of the reagent.
Keywords: bromination, microwave irradiation (MWI), regioselectivity, solvent free,
2,4,4,6-tetrabromo-2,5-cyclohexadienone (TBCHD), ultraviolet radiation
Received in India February 5, 2007
Address correspondence to Jasvinder Singh, Department of Chemistry, Punjab
University, Chandigarh 160014, India. E-mail: jsbrar_pu@yahoo.com
3421

3422
N. Gupta et al.
Brominated aromatic precursors are of paramount importance for the
synthesis[1] of various natural products, pharmaceuticals, and agrochemicals.
Numerous industrially valuable products such as fire retardants, insecticides,
herbicides, and pesticides are synthesized using different bromofunctional-
ities. Development of modern coupling reactions,[2] such as the Stille–
Suzuki, Tamao–Kumada, Heck, and Sonogashira reactions, has greatly
increased the demand for brominated aromatic compounds.
The traditional bromination reaction involves the direct use of elemental
bromine,[3] which generates corroding hydrogen bromide as a side product, a
substance that must be neutralized before it is discarded. Literature reports
various reagents for monobromination of aromatic compounds, which does
not make use of elemental bromine. N-bromosuccinamide (NBS),[4] under
different reaction conditions, has more often been used for allylic, benzylic,
photochemical, and aromatic bromination reactions.1-Butyl-3-methylimida-
zolium tribromide[5] ([bmim]Br3) has been used for the bromination of
phenols. Alkali metal bromides have been oxidized by various oxidizing
agents such as concentrated H2SO4 and NaClO2,[7] along with different
[6]
catalysts to get the monobrominated product of activated aromatic
compounds. Benzenehexabromide[8] and bromotrichloromethane[9] have
been used for the photochemical side-chain bromination of different
alkylated aromatic substrates.
Most of the methods require hazardous conditions, prolonged reaction
time, tedious workup, and expensive reagents. Thus, a milder, selective, inex-
pensive, and nonhazardous reagent that does not employ use of elemental
bromine is still in demand, and 2,4,4,6-tetrabromo-2,5-cyclohexadienone
(TBCHD) provides a key to this. We sought to extend the TBCHD
chemistry by a mild, selective, and straightforward reaction under solvent-
free conditions for different aromatic substrates. 2,4,4,6-Tetrabromo-2,5-
cyclohexadienone has earlier been used for the bromination of the aromatic
ring for aniline[10] and phenol[11] derivatives. Moreover, it is also known
for bromination of conjugated unsaturated ketones[12] along with its use in
other organic transformations such as preparation of azides[13] and
halides[14] and deprotection of acetals and ketals.[15] However, its use in
photochemical reactions[16] is very limited so far. Herein we report side-
chain and nuclear bromination of various activated arenes by the use of
TBCHD on solid support using photochemical and microwave energy for
the first time.
Bromination of arenes and heteroarenes is often an unselective reaction
resulting in a mixture of mono- and polybrominated derivatives with conse-
quent tedious separation and poor atom economy. Therefore, selectivity and
atom economy are the essential aspects in different synthetic endeavors, and
use of TBCHD provides a key to control the aforementioned aspects.
TBCHD was earlier prepared by the reaction of 2,4,6-tribromophenol[11]
with molecular bromine, which generates the corrosive hydrogen bromide,
but now a new methodology has been devised for its preparation from

Monobromination of Aromatic Compounds
3423
phenol[17] without using elemental bromine. Various advantages of the
reagent are its easy recyclability, atom economy, selectivity, moderate to
very short reaction time, and simple reaction setup.
Use of TBCHD in a photochemical reaction gives the monobrominated
product, uncontaminated with poly bromo or ring-substituted derivatives,
along with 2,4,6-tribromophenol as a side product, which can be recycled
easily to regenerate the reagent. Side-chain bromination was carried out by
adsorbing the reactants on silica and exposing them to ultraviolet light for 4
to 5 h (Scheme 1).
The reaction gives only the side-chain-substituted products, without the
formation of any ring-substituted product, in excellent yields with simple
workup. In the case of aromatic compounds containing both the alkyl group
and activating group, such as the hydroxyl group, only ring-substituted
products are formed. In the case of compounds with deactivating groups,
such as the nitro group, no nuclear or side-chain substitution is observed.
All the results have been tabulated (Table 1).
For the nuclear bromination of different aromatic compounds, reactants
are adsorbed on solid support and exposed to microwave radiations for a
few seconds (Scheme 2). Excellent yields are obtained for a range of
activated aromatic and heteroaromatic compounds, in very short reaction
time (Table 2). Results obtained are also compared with those of the conven-
tional method. The introduction of the electron-withdrawing group, as well as
moderate activating group, results in failure of the reaction.
The effect of a solid support during the nuclear bromination reaction was
also investigated, and the best results are obtained by the use of silica and
neutral alumina (Table 3). 2,4,6-Tribromophenol, the side product formed at
the end of the reaction, was used for the regeneration of TBCHD after extract-
ing it from the aqueous layer. Regenerated reagent was used three times with
good yields for the bromination of toluene and anisole (side-chain and nuclear
substitution, respectively). We also found that it has a long shelf life and works
well even after 6 months if stored in a cool and dark place.
In conclusion, a new method for side-chain and nuclear bromination of
activated aromatic compounds has been developed using TBCHD under
simple reaction conditions. The methodology provides a key to control the
selectivity by the use of microwave and ultraviolet energy, giving quantitative
yields, very fast to moderate reaction rates, and atom economy.
Scheme 1.

3424
N. Gupta et al.
Table 1. Photochemical side-chain bromination of different alkylated arenes using
2,4,4,6-tetrabromo-2,5-cyclohexadienone
Irradiation
time (h)
Yield
(%)
S. No
1
Substrate
Product
4
95
82
2
3
4.5
4.5
84
4
5
4
4
94
92
6
7
—
14
3
—
35
Note. All the compounds were characterized on the basis of 1H NMR and IR
spectral data, which were consistent with those reported in the literature.
EXPERIMENTAL
General Procedure for Side-Chain Bromination
TBCHD (2 mmol) was ground with silica (2.5 g) followed by dropwise
addition of substrate (2 mmol). It was ground well to be adsorbed uniformly
on the silica. Reaction mixture was transferred to a conical (250-mL)
container covered with a watch glass and exposed to ultraviolet radiation
Scheme 2.

Monobromination of Aromatic Compounds
3425
Table 2. Nuclear bromination of different aromatic and heteroaromatic compounds
using 2,4,4,6-tetrabromo-2,5-cyclohexadienone
MWI
(160 W)
Stirring at rt
Time Yield Time Yield
S. No
1
Substrate
Product
(h)
3
(%)
94
(s)
50
(%)
95
2
3
2
3
68
92
120
50
74
95
4
Polymerises
2
—
40
—
5
6
7
3
3
3
62
75
52
80
80
50
78
85
56
8
9
4
42
—
150
240
72
—
—
—
—
12
10
11
12
12
—
—
300
300
—
—
Notes. All the compounds were characterized on the basis of 1H NMR and IR
spectral data, which were consistent with those reported in the literature. Products 2
and 7 were identified on the basis of 13C NMR.

3426
N. Gupta et al.
Table 3. Yields of 4-bromoanisol on
different solid supports
S. No
Solid support
Yield (%)
1
2
3
4
5
6
Acidic alumina
Basic alumina
Neutral alumina
K-10 clay
92
94
96
82
88
96
KSF clay
Silica
for the time specified in Table 1. The resulting mixture was then shifted to a
short column and eluted with dichloromethane (3 Â 10 mL). The DCM layer
was washed with 5M NaOH solution (3 Â 15 mL), followed by water, and
dried. Evaporation of the solvent under reduced pressure yielded the
product in excellent yield. In the case of cresol, after irradiation, the
resultant mixture was directly separated via column chromatography using
hexane and ethyl acetate (9:1) as eluent.
General Procedure for Nuclear Bromination
TBCHD (2 mmol) was ground with silica (2.5 g) or neutral alumina (2.5 g)
until a light yellow powder was formed, followed by dropwise addition of
substrate (2 mmol). It was ground well and transferred to a conical (50-mL)
container covered with a watch glass. The resulting mixture was irradiated
with microwaves at 160 W for the time specified in Table 2 and worked up
as previously except for 6-hydroxy-4-methyl-2H-chromen-2-one[substrate 2
(Table 2)]. To obtain the monobromo derivative of substrate 2, the resulting
mixture was first eluted with DCM (3 Â 10 mL) followed by ethanol
(10 mL). The ethanol fraction was concentrated and left overnight to get
needle-shaped crystals of 7-bromo-6-hydroxy-4-methyl-2H-chromen-2-one.
Recycling of the Reagent
The aqueous layer was neutralized by dil. hydrochloric acid. When the
solution became slightly acidic, as indicated by pH paper, it was extracted
with DCM. The organic layer was dried and evaporated to yield 2,4,6-tribro-
mophenol (72%), which was used as such for preparing the reagent by the
reported method.

Monobromination of Aromatic Compounds
ACKNOWLEDGMENT
3427
Authors are thankful to University Grant Commission (UGC) and Council of
Scientific and Industrial Research (CSIR) New Delhi (India) for providing
financial assistance.
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