TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6941–6942
An efficient chemo and regioselective oxidative nuclear
bromination of activated aromatic compounds using lithium
bromide and ceric ammonium nitrate
a,
a
a
b
Subhas Chandra Roy, * Chandrani Guin, Kalyan Kumar Rana and Gourhari Maiti
a
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
b
Department of Chemistry, Jadavpur University, Jadavpur, Calcutta 700 032, India
Received 25 June 2001; accepted 27 July 2001
Abstract—A mild, efficient and highly chemo- and regioselective method for the bromination of electron rich aromatic molecules
+
has been developed by electrophilic substitution of Br , which was generated in situ from LiBr using ceric ammonium nitrate as
the oxidant. Free aromatic amines remained unaffected under the reaction conditions. © 2001 Elsevier Science Ltd. All rights
reserved.
1
Brominated arenes are versatile intermediates for the
synthesis of a wide variety of biologically active com-
In a typical reaction, a solution of CAN (2.8 g, 5.1
mmol) in CH CN (10 ml) was added dropwise to a
3
2
pounds. The direct bromination of activated aromatic
systems using Br generates toxic and corrosive hydro-
gen bromide, which causes serious environmental pollu-
tion. To overcome this problem, various methods of
oxidative nuclear bromination of aromatic molecules
have been developed including NBS–HZMS-5, NBS–
amberlyst and KBr–H O using metal-oxo catalysts.
Very recently, bromination using KBr–NaBO ·4H O,
and BuOBr–zeolite has also been reported. Some of
these methods suffer from harsh reaction conditions or
cumbersome extraction procedures, hence a milder and
better method is desirable. In addition to car-
bonꢀcarbon bond forming reactions, ceric ammonium
nitrate (CAN) has also been found to be a readily
available reagent for various valuable transformations
in organic synthesis. In addition to our continued
stirred mixture of anisole (500 mg, 4.63 mmol) and
anhydrous LiBr (443 mg, 5.1 mmol) in CH
CN (10 ml)
at room temperature under N . The reaction mixture
2
2
3
was stirred for 1 h. It was decomposed with water (10
ml) and was extracted with ether (3×25 ml). The com-
bined ether extract was washed successively with
3
4
5
6
aqueous NaHCO (2×10 ml), water (2×10 ml) and brine
3
2
2
(1×10 ml), and was dried (Na SO ). The solvent was
2
4
3
2
t
7
removed under reduced pressure and the residue was
purified by column chromatography over neutral alu-
mina (petroleum ether) to furnish pure p-bromoanisole
(
860 mg, 99%).
+
The electrophile Br is generated in situ by the reaction
of LiBr and CAN and attacks the electron-rich aro-
matic rings. While electron-rich arenes were brominated
smoothly, electron deficient aromatic compounds such
as anthranilic acid and methyl anthranilate remained
unaffected under the reaction conditions. Surprisingly,
free aromatic amines such as aniline and p-toluidine did
not respond at all. This is probably due to the forma-
tion of a salt of the free amine with the acidic CAN
which makes the aromatic ring electron deficient.
Although the protected aromatic amine (Table 1, entry
8
interest in exploring CAN as a powerful one-electron
oxidant, we report here a mild and efficient method for
the bromination of activated aromatic compounds by
using LiBr as the bromine source and CAN as the
oxidant. Thus, a series of aromatic compounds was
subjected to bromination in the presence of CAN and
LiBr in acetonitrile at room temperature to furnish the
corresponding bromo-arenes and the results are sum-
marized in Table 1.
6
) could be brominated in satisfactory yield, the reac-
tion was very slow with only 50% conversion even on
prolonged stirring. Some of the substrates (Table 1,
entry 1, 5 and 6) furnished a mixture of ortho and para
brominated compounds, the para isomer always pre-
dominated. In most of the substrates the bromination
was highly regioselective.
Keywords: chemo and regioselective; oxidative nuclear bromination;
lithium bromide; ceric ammonium nitrate.
Corresponding author. E-mail: ocscr@mahendra.iacs.res.in
*
0
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