Vilsmeier-haack bromination of aromatic compounds with KBr and N-bromosuccinimide under solvent-free conditions

Article abstract of DOI:10.1080/00397910802594268

Bromination of aromatic hydrocarbons is triggered by Vilsmeier-Haack reagent [N,N-dimethyl formamide (DMF-POCl3 system)] in the presence of KBr or N-bromosuccinimide (NBS) under solvent-free conditions by grinding the reactants in a mortar with a pestle. The reactions afforded corresponding bromo derivatives in very good yield with high regioselectivity. The results are comparable with those obtained under reflux conditions. Copyright Taylor & Francis Group, LLC.

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Vilsmeier–Haack Bromination of
Aromatic Compounds with KBr
and N-Bromosuccinimide Under
Solvent-Free Conditions
a
a
a
A. Chakradhar , R. Roopa , K. C. Rajanna & P. K.
b
Saiprakash
a
Osmania University Postgraduate College, Mirzapur,
India
b
Department of Chemistry, Osmania University,
Hyderabad, India
Version of record first published: 15 Apr 2009.
To cite this article: A. Chakradhar , R. Roopa , K. C. Rajanna & P. K. Saiprakash
(2009): Vilsmeier–Haack Bromination of Aromatic Compounds with KBr and N-
Bromosuccinimide Under Solvent-Free Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:10,
1817-1824
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1
Synthetic Communications , 39: 1817–1824, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802594268
Vilsmeier–Haack Bromination of Aromatic
Compounds with KBr and N-Bromosuccinimide
Under Solvent-Free Conditions
1
A. Chakradhar, R. Roopa, K. C. Rajanna, and P. K. Saiprakash
1
1
2
1
Osmania University Postgraduate College, Mirzapur, India
Department of Chemistry, Osmania University, Hyderabad, India
2
Abstract: Bromination of aromatic hydrocarbons is triggered by Vilsmeier–
Haack reagent [N,N-dimethyl formamide (DMF–POCl system)] in the presence
3
of KBr or N-bromosuccinimide (NBS) under solvent-free conditions by grinding
the reactants in a mortar with a pestle. The reactions afforded corresponding
bromo derivatives in very good yield with high regioselectivity. The results are
comparable with those obtained under reflux conditions.
Keywords: Bromination, KBr, N-bromosuccinimide, solvent-free conditions,
Vilsmeier–Haack reagent
INTRODUCTION
Over the years, bromination of aromatic compounds has been an area of
interest to chemists because bromo arenes are useful intermediates in the
synthesis of organometallic species and pharmaceutically important com-
[
1–3]
pounds.
Direct methods of bromination of aromatic compounds
involve the use of hazardous molecular bromine that is toxic, is corrosive,
and pollutes to the environment, and metal ion catalysts are generally
expensive. In view of this, there has been an upsurge in the design and
[
4–13]
execution of mild methods of bromination of aromatic compounds.
Received August 16, 2008.
Address correspondence to K. C. Rajanna, Osmania University Postgraduate
College, Mirzapur, SGD 502 249, India. E-mail: kcrajannaou@rediffmail.com
1
817

1818
A. Chakradhar et al.
Over the past decade, our group has also been actively involved
in designing a variety of ecofriendly materials using micelle-forming
surfactants as catalysts and unconventional energy sources (such as micro-
[
14]
waves and ultrasound) to assist Vilsmeier–Haack (VH) reactions
[15,16]
Hunsdiecker reactions.
and
Dramatic rate accelerations followed by an
increase in the product yield were observed in these reactions in all cases.
It is of interest to note that certain VH reactions could be effectively com-
pleted in 2 to 3 min under sonication and microwave irradiation. Organic
reactions performed under solvent-free conditions have gained much att-
ention because of their enhanced selectivity, mild reaction conditions, and
[
16–18]
associated ease of manipulation. The recent reviews and publications
in this field prove the importance of solvent-free organic synthesis and
highlights that this process is not only simple but also satisfies both eco-
nomical and environmental demands by replacing the toxic solvents.
Encouraged by these results, we present bromination of certain aromatic
hydrocarbons, amines, and anilides under VH conditions using KBr and
N-bromosuccinimide (NBS) as source of bromine species.
RESULTS AND DISCUSSION
[14,19–21]
The VH reaction
is widely used for formylations. It can also be
applied to introduce an acetyl group on activated aromatic or hetero aro-
matic compounds, many other conversions can be achieved with this
technology. In general, N,N-dimethylformamide (DMF) and phosphorus
oxychloride (POCl ) are used to generate a halomethyleniminium salt
3
[14,19–21]
used in the synthesis of a large number of heterocyclic compounds.
The VH reaction is a mild method known for the introduction of a formyl
group to various activated aromatic and hetero aromatic compounds.
VH reagent, aromatic compound, and KBr or NBS are ground in a mor-
tar with a pestle to afford the corresponding bromo derivatives in good
yields. Similarly, when aromatic amines and acetanilides were used as
substrates, the reactions afforded the corresponding bromo anilines
and bromo acetanilides (Scheme 1) in good yields (Table 1).
Scheme 1. X represents the functional group and R represents the electron-
donating group.

1
819

1820
A. Chakradhar et al.
Scheme 2. X ¼ -OH, -NH
2
and R represents the electron-donating group.
The reaction rapidly afforded high yields of the corresponding
5 bromo derivatives. All the products were characterized by infrared
(
authentic samples and found to be satisfactory (Table 2).
5
1
IR), H NMR, mass spectra (MS), and physical data comparisons with
To compare these results, aromatic compounds were treated with
VH adduct POCl =DMF in ClCH CH Cl under reflux conditions.
3
2
2
These reactions also the afforded the corresponding bromo derivatives
in good yields. Similarly, when aromatic amines and acetanilides were
reacted with POCl =DMF in the presence of NBS or KBr, the reaction
3
indicated corresponding bromo derivatives (Scheme 2, Table 1).
The reaction proceeded rapidly with POCl =DMF=NBS over
3
POCl =DMF=KBr to afford high yields of the corresponding bromo
3
derivatives. Data summarized in Table 1 clearly demonstrate that the
obtained yields are good to excellent; the POCl =DMF=NBS system
3
afforded relatively better yields than the POCl =DMF=KBr system. This
3
þ
may be because the active electrophile (Br ) is released faster in the case
of the POCl =DMF=NBS system and is available for favorable bromina-
3
tion over the POCl =DMF=KBr system. Not only activated aromatic but
3
also deactivated aromatic compounds were brominated efficiently. It is
interesting to note that the results obtained under solvent-free conditions
are by and large comparable with solution-phase reactions under reflux
conditions.
CONCLUSIONS
In summary, we have demonstrated that bromination of aromatic
compounds occurred smoothly with VH reagent and KBr=NBS under
solvent-free conditions to afford the products in moderate to good yields.
The results are comparable with those obtained under solution-phase
conditions. The present finding is a major breakthrough as the reaction
occurs under very mild and solvent-free conditions with a simple and
clean workup.

1
821

1822
A. Chakradhar et al.
EXPERIMENTAL
All chemicals were of research grade and were used as obtained from
Aldrich, Lancaster, Fluka, or local companies. Melting points were recor-
ded on an electrothermal meltingz point apparatus and are uncorrected.
IR spectra were recorded on KBr pellets, mass spectra were recorded on
1
a VG 7070H Micromass mass spectrometer, and H NMR spectra were
recorded on a Brukner 200-MHz spectrometer.
General Procedure for Bromination of Aromatic Compounds Under
Solvent-Free Conditions
A VH adduct prepared from POCl (9.3 ml, 100 mmol) and DMF
3
ꢁ
(
9.29 ml, 100 mmol) at ꢀ5 C was slowly added to phenol (1 d) (50 mmol)
and KBr (or NBS) in a mortar and ground with a pestle. After comple-
tion of the reaction as indicated by thin-layer chromatography (TLC), the
reaction mixture was dissolved in chloroform or dichloromethane and
quenched with sodium thiosulphate solution. The organic layer was
separated, dried over Na SO , evaporated under a vacuum, and purified
2
4
with column chromatography using chloroform–hexane (9:1) as eluent to
get pure product.
General Procedure for Bromination of Aromatic Compounds Under
Reflux Conditions
A VH adduct prepared from POCl (9.3 ml, 100 mmol) and DMF
3
ꢁ
(
(
9.29 ml, 100 mmol) at ꢀ5 C was slowly added to a solution of phenol
1 d) (50 mmol) and KBr (or NBS) in dichloroethane and refluxed. After
completion of the reaction as indicated by TLC, the reaction mixture was
quenched with sodium thiosulphate solution. The organic layer was
separated, dried over Na SO , evaporated under vacuum, and purified
2
4
with column chromatography using chloroform–hexane (9:1) as eluent
to get pure product.
ACKNOWLEDGMENTS
The authors thank Prof. T. Navaneeth Rao (former vice-chancellor,
Osmania University, Hyderabad) and the Management Committee of
Siddhartha P. G. College, Hyderabad, for constant encouragement. The
authors thank the council of scientific and Industrial research (CSIR),

Bromination of Aromatic Compounds
1823
New Delhi, for financial assistance in the form of an emeritus scientist
appointment accorded to Prof. P. K. Saiprakash.
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