Studies on bromination of active methylene by a mixture of hydrobromic acid and hydrogen peroxide (or TBHP)

Article abstract of DOI:10.1081/SCC-120018701

Studies on bromination of active methylene with a mixture of hydrogen peroxide or tert-butylhydroperoxide (TBHP) and hydrobromic acid are discussed. Substituted acetophenones, benzocyclic ketones provide α-bromo-keto compounds in high yields under this re

Full text of DOI:10.1081/SCC-120018701

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Studies on Bromination of Active Methylene by a
Mixture of Hydrobromic Acid and Hydrogen Peroxide
(
or TBHP)
a
a
a
a
Vasudha H. Tillu , Popat D. Shinde , Ashutosh V. Bedekar & Radhika D. Wakharkar
a
Division of Organic Chemistry: Technology , National Chemical Laboratory , Pune, India
Published online: 15 Aug 2006.
To cite this article: Vasudha H. Tillu , Popat D. Shinde , Ashutosh V. Bedekar & Radhika D. Wakharkar (2003) Studies
on Bromination of Active Methylene by a Mixture of Hydrobromic Acid and Hydrogen Peroxide (or TBHP), Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:8, 1399-1403, DOI:
10.1081/SCC-120018701
To link to this article: http://dx.doi.org/10.1081/SCC-120018701
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 8, pp. 1399–1403, 2003
Studies on Bromination of Active Methylene by
a Mixture of Hydrobromic Acid and
Hydrogen Peroxide (or TBHP)
Vasudha H. Tillu,Popat D. Shinde,Ashutosh V. Bedekar,
and Radhika D. Wakharkar*
Division of Organic Chemistry: Technology,
National Chemical Laboratory, Pune, India
ABSTRACT
Studies on bromination of active methylene with a mixture of hydro-
genperoxide or tert-butylhydroperoxide (TBHP) and hydrobromic
acid are discussed. Substituted acetophenones, benzocyclic ketones
provide a-bromo-keto compounds in high yields under this reaction
condition.
Key Words: Oxyhalogenation; Active methylene; H O ; TBHP; HBr.
2
2
*Correspondence: Radhika D. Wakharkar, Division of Organic Chemistry:
Technology, National Chemical Laboratory, Pune 411 008, India; Fax:
þ91-20-5893614; E-mail: rdw@dalton.ncl.res.in.
1
399
DOI: 10.1081/SCC-120018701
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1
400
Tillu et al.
[1]
We have reported a simple and efficient protocol for the halogena-
tion of arenes, alkenes, and alkynes using a combination of hydrohalic
acid and hydrogen peroxide or tert-butylhydroperoxide (TBHP).
During the studies on the oxyhalogenation of variously substituted
[1]
arenes using our protocol whenacetophe no ne was subjected to bromi-
nation reaction, side chain bromination was preferred over aromatic
bromination. The scope and generality of this observation is discussed
in the present communication.
RESULTS AND DISCUSSION
Table 1 depicts the results of bromination of active methylenes (a- to
keto group) in substituted acetophenones. It was found that they undergo
a-bromination (Table 1, Entries 1–7) in high yields using hydrogen
peroxide or TBHP as oxidants.
However, acetophenones with free hydroxyl function (phenolic,
Entries 8 and 9) resulted into aromatic bromination, which is in agreement
[1]
with our earlier observation. TBHP exhibited excellent selectivity for
monobromination in case of cyclic ketones (Sch. 1) viz. indanone and
tetralone (Entries 11 and 12) whereas H O was required inlarge excess
2
2
(
E nt ry 10) for completionof reactionwhich fur ni shed the dibromi na ted
product as the single product in 89% yield. The reagent was found to be
selective for bromination of active methylene as no bromination of
benzylic positions was observed. Similar difference in the activity of the
oxidants was observed and discussed in our previous publications. It is
noteworthy that bromination of ethyl acetoacetate could be controlled
(Entry 13) to obtain only monobrominated product in 99% yield in the
presence of several vulnerable positions for bromination.
EXPERIMENTAL
General Procedure
Progress of reactions was monitored by TLC using Merck silica gel
0 F254 precoated plates and spots were visualized under UV light or on
6
exposure to I vapors. NMR spectra were recorded at 200 MHz inCDCl 3
2
using TMS as internal standard. Hydrogen peroxide (30% w/v) was
procured from Asian chemicals, India and tert-butylhydroperoxide
(
TBHP, 70% w/v) was obtained from Aldrich Chemicals, India.

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Bromination of Active Methylene by TBHP
1401
Table 1.
Reaction
condition
a
Entry
1
Substrate
Product
% yield
Dioxan
95
85
93
87
75
94
90
90
98
89
65
64
99
HBr (1.5)
H O (1.1)
Dioxan
2
2
2
3
4
5
6
7
8
9
HBr (1.1)
TBHP (1.1)
Dioxan
HBr (1.1)
2 2
H O (1.1)
Dioxan
HBr (1.1)
TBHP (1.1)
Dioxan
HBr (1.5)
2 2
H O (1.1)
Dioxan
HBr (1.1)
2 2
H O (1.1)
Dioxan
HBr (1.1)
TBHP (1.1)
Dioxan
HBr (1.5)
2 2
H O (1.1)
Dioxan
HBr (1.2)
2 2
H O (1.1)
10
11
12
13
Methanol
HBr (4.0)
2 2
H O (4.0)
Dioxan
HBr (1.1)
TBHP (1.1)
Dioxan
HBr (1.1)
TBHP (1.1)
CH
HBr (1.5)
(1.1)
2 2
Cl
2 2
H O
a
Isolated yield, characterized by usual spectral analysis.

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402
Tillu et al.
Scheme 1.
Aqueous hydrobromic acid (47%) was purchased fiom S.D. Fine
Chemicals, India.
Preparation of 2 Bromo-1-(4-methylphenyl)-l-ethanone
(Table 1: Entry 4)
A solutionof TBHP (70% aq. 0.25 mL 2 mmol ) was added to a
cooled mixture of HBr (48% aq. 0.34 mL, 2 mmol) indioxan(5 mL)
and the mixture stirred for 5 min. To this cold solution 4-methylphe-
nyl-1-ethanone (0.268 g, 2 mmol) was added, stirred at same temperature
for 30 mina nd thenrefluxed for 20 h. Oncompletionof reaction(TLC)
the solvent was evaporated and the product was taken in 5 mL water,
extracted with EtOAc (3 ꢀ 10 mL) washed with water and brine, dried on
sodium sulphate and concentrated on rotary evaporator to afford a yel-
lowish solid. The product was purified by flash colum chromatography
over silica gel to afford pure product (0.370 g, 86.85%). IR: ꢀ 2991.83,
ꢁ
922, 1659, 1583, 1171, 650 cm , H NMR: (CDCl ) ꢁ 2.4 (s, 3H) 4.4
3
1 1
2
(
s, 2H), 7.22–7.27 (m, 2H), 7.84 (m, 2H ). MS (m/z): 212 (Mþ), 164 (20),
119 (100), 105 (20), 91 (100), 77 (20), 65 (50). Elemental analysis:
Calculated for C H BrO, C: 50.70, H: 4.22, Br: 37.08, Found C: 51.25,
H: 4.29, Br: 37.06.
9
9
In conclusion we have demonstrated regioselective bromination of
active methylene in high yields by applying a combination of hydrobromic
acid and hydrogen peroxide or TBHP under mild reaction condition in
high yield. This method provides simple work-up, easy purificationand
economical process for industrial applications.
ACKNOWLEDGMENT
A. V. B. and P. D. S. wish to thank CSIR New Delhi for the award of
Pool Officership and Senior Research Fellowship, respectively.

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Bromination of Active Methylene by TBHP
REFERENCE
. (a) Barhate, N.B.; Garjare, A.S.; Wakharkar, R.D.; and Bedekar.
1403
1
Simple and practicle halogenation of arenes, alkenes, and alkynes
with hydrohalic acid/H O (or TBHP). A.V. Tetrahedron 1999, 55,
2
2
11127; (b) Barhate, N.B.; Gajare, A.S.; Wakharkar, R.D.; Bedekar.
Simple and efficient chlorination and bromination of aromatic com-
pounds with aqueous TBHP (or H O ) and a hydrohalic acid. A.V.
TetrahedronLett. 1998, 39, 6349.
2
2
Received in the Netherlands June 5, 2002

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