A new regioselective bromination of activated aromatic rings

Article abstract of DOI:10.1055/s-2005-918511

An efficient and highly regioselective bromination of activated aromatic rings promoted by tribromoisocyanuric acid by in situ generation of Br ⁺ has been developed. A range of aromatic compounds were reacted with tribromoisocyanuric acid and trichloroisocyanuric acid and sodium bromide. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-918511

SHORT PAPER
221
A New Regioselective Bromination of Activated Aromatic Rings
Regioselective
B
e
rominatio
o
n
nardo S. de Almeida, Pierre M. Esteves,* Marcio C. S. de Mattos*
Instituto de Química, Departamento de Química Orgânica, Universidade Federal do Rio de Janeiro, Cx. Postal 68545, 21945-970
Rio de Janeiro, Brazil
Fax +55(21)25627133; E-mail: mmattos@iq.ufrj.br; E-mail: pesteves@iq.ufrj.br
Received 27 June 2005; revised 28 July 2005
X
Abstract: An efficient and highly regioselective bromination of ac-
O
X
N
O
X
tivated aromatic rings promoted by tribromoisocyanuric acid by in
situ generation of Br+ has been developed. A range of aromatic
compounds were reacted with tribromoisocyanuric acid and
trichloroisocyanuric acid and sodium bromide.
Cl (TCCA)
Br (TBCA)
X =
N
N
O
Key words: aromatic rings, bromination, trichloroisocyanuric acid,
tribromoisocyanuric acid
Figure 1 Trihaloisocyanuric acids.
ide) at room temperature gave after work-up the corre-
sponding monobromo arenes in good to excellent yields
(Table 1). The regioselectivity in both reactions was very
high and no regioisomers were detected by the analytical
procedures employed (HRGC and 1H and 13C NMR spec-
troscopy). However, in the case of TCCA/Br–, traces of
chlorinated products were detected (checked by coinjec-
tion with authentic samples by HRGC).
The direct halogenation1 of aromatic rings employs halo-
gens in the X2 form and generates HX, which are very tox-
ic, corrosive, and polluting agents. In order to decrease
toxic waste, some papers report alternative electrophilic
halogenating reagents, such as N-halosuccinimides2 and
N-halosaccharines,3 which are stable, easy to manipulate,
and produce less toxic imides as by product. Some inter-
esting methodologies for bromination of aromatic rings
also involve in situ generation of Br+ by oxidation of a
bromide ion by nitric acid,4a hydrogen peroxide,4b and
Oxone®.4c
Both reactions are very simple and the products from the
reaction using TCCA/Br– are easily purified by recrystal-
ization from hexane. On the other hand, when using TB-
CA, the products are pure, needing no further purification.
Trichloroisocyanuric acid5 (TCCA) (Figure 1), an inex-
pensive solid used as a bleaching agent, in disinfectants,
and as a bactericide, is an interesting compound due to its
function as a chlorinating agent and oxidant. TCCA was
first reported for the electrophilic halogenation of aromat-
ic systems in the presence of catalysts by Juenge et al.6
Bromination of some aromatic compounds by mono- or
dibromoisocyanuric derivatives are described in the liter-
ature.7 To the best of our knowledge, tribromoisocyanuric
acid (TBCA) (Figure 1), an analogue of TCCA synthe-
sized by Gottardi,8 has not yet been reported as a bromi-
nating agent. These haloisocyanuric acids are very
interesting from the green chemistry point of view,9 as it
is possible to halogenate organic compounds10 without us-
ing X2. They also have advantages from the view point of
atom economy, as they can transfer the majority of their
mass to the substrate, for example, TBCA can transfer up
to 65% of its mass.
In general, reactions with TCCA/Br– are faster than with
TBCA, due to the in situ generated Br+, which is more
electrophilic than the bromine atom in TBCA. The solu-
bility of the substrates and sodium bromide, as well as the
polar protic solvents employed seemed to influence the re-
action time; when the reaction was attempted with other
solvents, very low conversions were observed.
Non-activated or weakly activated arenes failed to under-
go bromination or were brominated slowly. The reaction
of toluene with TBCA, for example, gave traces of bromi-
nated products in 72 hours while the reaction with ben-
zene gave no product after 168 hours (Table 1).
In conclusion, the present method proved to be an effi-
cient and ecofriendly alternative for the regioselective
bromination of activated aromatic rings in good to excel-
lent yields. The reaction conditions are mild and the meth-
od is simpler then the traditional routes employed to
synthesize these compounds from arenes. Furthermore,
the reagents are inexpensive, readily prepared, very safe,
and more useful in terms of atom economy than the tradi-
tional reagents used in bromination reaction.
In this paper, we describe a new methodology for the re-
gioselective bromination of activated aromatic rings using
TCCA in bromide and TBCA as the source of Br+.
The reaction of arene and TBCA or TCCA and sodium
bromide, in methanol or water (just for N-methylacetanil-
TBCA was prepared analogously to N-bromosaccharine.3a Trichlor-
oisocyanuric acid (commercial grade, 98%), and other chemicals
and solvents were used as received. The 1H and 13C spectra were re-
corded on a Bruker AC-200 (200 MHz and 50 MHz, respectively)
spectrometer in CDCl3 or DMSO-d6 with TMS as the internal stan-
dard. GC was performed on a HP-5890-II gas chromatograph with
SYNTHESIS 2006, No. 2, pp 0221–0223
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Advanced online publication: 21.12.2005
DOI: 10.1055/s-2005-918511; Art ID: M04205SS
© Georg Thieme Verlag Stuttgart · New York

222
L. S. de Almeida et al.
SHORT PAPER
Table 1 Bromination of Activated Aromatic Rings
conditions
r.t.
Ar
H
Ar Br
Substrate
Product
Conditions
Yield (%)a
OCH3
OCH3
NMeAc
NHAc
TBCA, MeOH, 2 h
TCCA, NaBr, MeOH, 1 h
98
89
1
2
Br
Br
Br
NHAc
NHAc
TBCA, H2O, 24 h
TCCA, NaBr, H2O, 1 h
80
85
TBCA, MeOH, 72 h
TCCA, NaBr, MeOH, 18 h
81
83
3
4
Br
OCH3
TBCA, MeOH, 0.5 h
TCCA, NaBr, MeOH, 0.5 h
90
90
OCH3
TBCA, MeOH, 72 h
TBCA, MeCN, 72 h
TCCA, NaBr, MeOH, 72 h
Trace
Trace
Trace
CH3
CH3
5
6
Br
TBCA, MeOH, 168 h
TCCA, MeCN, 168 h
TCCA, NaBr, MeOH, 168 h
No reactionb
No reactionb
No reactionb
–
a Isolated yield based on arene.
b Substrate was recovered.
FID using a 30 m (length), 0.25 mm (ID), by 25 mm (phase thick-
ness) RTX-5 capillary column and H2 (flow rate 50 cm/s) as carrier
gas (split: 1:10).
4-Bromoacetanilide
Mp 166 °C (lit.12 167 °C).
1H NMR (DMSO-d6): d = 2.03 (s, 3 H), 7.43, (d, J = 8.92 Hz, 2 H),
7.54 (d, J = 8.92 Hz, 2 H).
13C NMR (DMSO-d6): d = 24.0 (CH3), 114.5 (C), 120.8 (CH),
131.5 (CH), 138.7 (C), 168.5 (C=O).
Reaction of Arenes with TBCA or TCCA/Br–; General
Procedure
To a stirred solution of arene (5 mmol) in MeOH (25 mL) or H2O
(50 mL, for N-methylacetanilide), was added TBCA (1.67 mmol) or
TCCA (1.85 mmol) and NaBr (6 mmol) at r.t. in small portions. The
reaction was monitored by GC. After the time shown in Table 1,
CH2Cl2 (30 mL) and H2O (50 mL) were added, cyanuric acid was
filtered off, and the resulting solution was treated with 10% aq
Na2SO3 (20 mL). The aqueous phase was washed with CH2Cl2
(2 × 30 mL) and the combined organic layer was dried over anhyd
Na2SO4. After evaporation of the solvent on a rotary evaporator, the
product was collected.
1-Bromo-2-methoxynaphthalene
Mp 82 °C (lit.13 85 °C).
1H NMR (CDCl3): d = 4.03 (s, 3 H), 7.26 (d, J = 9.67 Hz, 1 H), 7.41
(t, J = 7.90 Hz, 1 H), 7.59 (t, J = 7.90 Hz, 1 H), 7.80 (d, J = 7.9 Hz,
1 H), 7.81 (d, J = 9.67 Hz, 1 H), 8.26 (d, J = 7.90 Hz, 1 H).
13C NMR (CDCl3): d = 56.9 (CH3), 108.6 (C), 113.6 (CH), 124.2
(CH), 126.0 (CH), 127.7 (CH), 128.0 (CH), 128.9 (CH), 129.8 (C),
133.0 (C), 153.7 (C).
4-Bromoanisole
1H NMR (CDCl3): d = 3.77 (s, 3 H), 6.78 (d, J = 8.90 Hz, 2 H), 7.37
(d, J = 8.90 Hz, 2 H).
Acknowledgment
Authors thank CAPES, CNPq, and FAPERJ for financial support.
13C NMR (CDCl3): d = 55.4 (CH3), 112.8 (C), 115.7 (CH), 139.2
(CH), 158.7 (C).
References
4-Bromo-N-methylacetanilide
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13C NMR (CDCl3): d = 22.4 (CH3), 37.0 (CH3), 121.4 (C), 128.7
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Synthesis 2006, No. 2, 221–223 © Thieme Stuttgart · New York

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