Superelectrophilic bromination of deactivated aromatic rings with tribromoisocyanuric acid-an experimental and DFT study

Article abstract of DOI:10.1016/j.tetlet.2009.02.010

The reaction of deactivated arenes with tribromoisocyanuric acid (TBCA) in 98% H₂SO₄ produced bromoarenes in good yields. The acidity of the medium controls the strength of the brominating agent and the amount of polybrominated products. DFT calculations at B3LYP/6-311++G^** level showed that the protonated TBCA (a superelectrophilic species) can easily transfer Br⁺ to deactivated arenes, in order to decrease internal charge-charge repulsion.

Full text of DOI:10.1016/j.tetlet.2009.02.010

Tetrahedron Letters 50 (2009) 3001–3004
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Superelectrophilic bromination of deactivated aromatic rings
with tribromoisocyanuric acid—an experimental and DFT study
*
*
Leonardo 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
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of deactivated arenes with tribromoisocyanuric acid (TBCA) in 98% H2SO4 produced bromo-
arenes in good yields. The acidity of the medium controls the strength of the brominating agent and the
amount of polybrominated products. DFT calculations at B3LYP/6-311++G** level showed that the proton-
ated TBCA (a superelectrophilic species) can easily transfer Br+ to deactivated arenes, in order to decrease
internal charge–charge repulsion.
Received 7 January 2009
Revised 23 January 2009
Accepted 2 February 2009
Available online 8 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Deactivated arenes
Electrophilic bromination
DFT
SEAr
Bromoarenes are very useful intermediates in organic synthesis,
since they can be efficiently converted into a series of other func-
tionality by well known methodologies such as halogen–metal ex-
change,1 palladium-catalyzed Heck and related couplings,2 and
radical nucleophilic substitution.3 There are many known methods
for the bromination of aromatic rings, especially electron-rich sys-
tems.4 However, severe experimental conditions are required for
the halogenation of deactivated arenes.
N-Halo compounds are reported to react with activated arenes
to produce efficiently haloarenes.5 The halogenation of deactivated
aromatic rings with N-halo compounds promoted by strong acids
has also been reported.6 During the past decade, Olah and Klumpp
have carried out extensive experimental as well as theoretical
studies on superelectrophilic activation of electrophiles by proto-
solvation with superacidic systems, allowing electrophilic reac-
tions to take place with weakly nucleophilic substrates.7
The tribromoisocyanuric acid (TBCA, Fig. 1) is an efficient source
of electrophilic bromine (Br+) that has been used for the brominat-
ing 1,3-dicarbonyl compounds8 and activated aromatic rings,9
dibromination10 and cobromination11 of alkenes, and also in di-
verse oxidation reactions.12 TBCA is a stable solid that can be easily
synthesized from isocyanuric acid and NaBr in the presence of ox-
oneÒ.10 It has the advantage of high atom economy in comparison
to similar systems such as N-bromosuccinimide (NBS) and 3,3-di-
bromo-5,5-dimetilidantoin (DBH). Furthermore, in the reactions
involving TBCA, isocyanuric acid left at the end of the reaction as
a by-product can be recovered by filtration and reused to produce
more TBCA.11
Continuing our interest in electrophilic halogenation using tri-
haloisocyanuric acids,13 in the present work, we show our results
on the reaction of deactivated aromatic rings with TBCA under
strong acidic conditions (98% H2SO4).
The results of the bromination of some deactivated arenes with
0.34 mol equiv of TBCA in 98% H2SO4 at room temperature are
shown in Table 1.14 Nitrobenzene does not react with TBCA at ordin-
ary conditions. On the other hand, it can easily be brominated if the
reaction is performed in 98% H2SO4 to produce mainly m-bromoni-
trobenzene along with dibrominated products in small quantities.
Bromination of m-dinitrobenzene occurs nicely even at room
temperature in 98% H2SO4 affording the monobrominated product
in 79% yield. On the other hand, the reaction with 1,3,5-trinitroben-
zene does not occur, meaning that the electrophilic species is still
lacking reactivity to brominate such highly deactivated system.
The above results show that acid catalysis plays an important role
in the reaction of TBCA with deactivated arenes. TBCA can be O-pro-
tonated with strong Brønsted acids to form a superelectrophilic
O
Br
Br
O
N
N
O
N
Br
Figure 1. Tribromoisocyanuric acid (TBCA).
* Corresponding authors. Fax: + 55 21 25627133 (M.C.S.M.).
E-mail addresses: pesteves@iq.ufrj.br (P.M. Esteves), mmattos@iq.ufrj.br (M.C.S.
Mattos).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.010

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L. S. de Almeida et al. / Tetrahedron Letters 50 (2009) 3001–3004
Table 1
Table 2
Bromination of deactivated arenes with TBCA in 98% H2SO4
Enthalpy difference (298 K, 1 atm) for bromenium release from TBCA and its
protonated species
O
a
Reaction
D
H298
Br
Br
O
N
N
(kcal/mol)
O
O
O
N
Br
Br
O
Br
Br
N
N
N
N
N
N
N
N
+
+
269.5
Arene
Br
Br
98% H2SO4 / r.t.
O
N
O
N
O
O
Arene
Product
T (h)
Yielda (%)
69b
Br
Br
O
O
NO2
NO2
Br
Br
O
Br
4
154.0
H
H
H
H
O
N
O
N
Br
Br
Br
NO2
NO2
H
N
H
N
4
4
79
—
O
O
Br
Br
O
Br
NO2
NO2
Br
NO2
N
N
41.3
+
Br
O
N
O
N
O
Br
Br
—
O2N
NO2
H
H
O
O
Br
Br
Br
Br
N
N
N
N
F
F
F
F
À33.9
+
Br
F
F
O
F
H
H
O
N
O
O
N
O
1
52
75
H
Br
H
Br
F
F
Performed at the B3LYP/6-311++G**//B3LYP/6-31++G** level, taking into account
F
a
zero-point energy and thermal expansion correction.
O
0.3
Cl
Cl
O
Br
Br
Br
O
a
Yield of pure product based on arene.
Formed along with minor amount of dibromonitrobenzenes (<10%, by HRGC).
N
N
b
NO2
Br
NO2
O
N
Br
Br
Br
Br
Br
trication at the limit (Scheme 1) or a protosolvated analog, which
can act as an efficient bromenium-transfer agent. This highly
reactive species is able to attack even relatively unreactive arene
nucleophiles. The driving force for the Br+ release from protonated
TBCA is believed to be due to the decrease in internal charge–
charge repulsion.
85%
7% oleum
2min / r.t.
Scheme 2.
H
N
H
N
H
O
O
O
O
Br
N
H
O
Br
O
"H+"
"H+"
Br
Br
O
Br
Br
O
"H+"
Br
Br
O
N
N
N
N
N
N
O
N
O
N
O
N
Br
H
Br
Br
H
Br
H
H
O
N
H
N
O
O
Br
N
H
O
Br
Br
Br
O
N
Br
Br
O
N
N
N
O
O
N
O
N
Br
H
Br
H
Br
Scheme 1.

L. S. de Almeida et al. / Tetrahedron Letters 50 (2009) 3001–3004
3003
Figure 2. DFT calculations of transfer of Br+ from TBCA and protonated species to benzene. All structures correspond to minima on the respective potential energy surface.
In order to verify such hypothesis, we investigated the reaction
by DFT (density functional theory, see Supplementary data for
computational details) calculations on TBCA and its protonated
species that could estimate their ability to release Br+, and hence
would be correlated with its reactivity as an electrophile. DFT cal-
culations at B3LYP/6-311++G**//B3LYP/6-31++G** level showed
that the enthalpy change for the release of Br+ from polyprotonated
species of TBCA becomes more exothermic with the increase in
protonation degree leading to a more reactive intermediate (Table
2). This can be attributed to the relief of the coulombic (charge–
charge) repulsion within the polyprotonated TBCA upon Br+ trans-
fer to the substrate. As expected, N–Br bond length increases from
TBCA (1.860 Å) to the triprotonated species (1.898 Å) as a reflection
of the coulombic repulsion (Fig. S1 in Supplementary data).
Hence, the highly protonated TBCA-species works as a very
powerful electrophile, whose reactivity can be regulated by the
acid strength of the medium. As an example, nitrobenzene reacted
with excess TBCA in 7% oleum to produce pentabromonitrobenzene
in only 2 min at room temperature (Scheme 2).15 Unfortunately,
once more, 1,3,5-trinitrobenzene also did not react under these
conditions.
Acknowledgment
We thank CNPq for fellowships and financial support.
Supplementary data
Optimized geometries for TBCA and its protonated species;
CPMAS 13C NMR spectrum of TBCA; 13C NMR spectrum of TBCA
in 98% H2SO4; 13C NMR chemical shifts calculated for TBCA and
its protonated species and computational details are available.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.02.010.
References and notes
1. Leroux, F.; Schlosser, M. Angew. Chem., Int. Ed. 2002, 41, 4272.
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Wang, Q.; Rasul, G.; Olah, G. A. J. Am. Chem. Soc. 2004, 126, 15770; Rajesh, K.;
Somasundaram, M.; Saiganesh, R.; Balasubramanian, K. K. J. Org. Chem. 2007,
72, 5867; Haloisocyanuric acids (b) Mendonca, G. F.; Magalhães, R. M.; de
Mattos, M. C. S.; Esteves, P. M. J. Braz. Chem. Soc. 2005, 16, 695; Hubbard, A.;
Okazaki, T.; Laali, K. K. Austr. J. Chem. 2007, 60, 923; Gottardi, W. Monatsh.
Chem. 1969, 100, 42; DBH (c) Eguchi, H.; Kawaguchi, H.; Yoshinaga, S.; Nishida,
A.; Nishiguchi, T.; Fujisaki, S. Bull Chem. Soc. Jpn. 1994, 67, 1918.
7. Olah, G. A.; Klumpp, D. A. Acc. Chem. Res. 2004, 37, 211.
The transfer of Br+ from TBCA to the benzene ring using DFT cal-
culations (B3LYP/6-31++G** level) is not possible (Fig. 2). It was
also observed that increasing the protonation degree of TBCA led
to the increase in the N–Br bond length whilst Br–C (from benzene)
decreases significantly. In other words, based on coulombic repul-
sion, Br+ transferring to benzene is much more effective in proton-
ated species. However, transfer of Br+ from the triprotonated
species is strongly repelled by the intermediate (coulombic explo-
sion) suggesting that this species is not formed.
The CPMAS 13C NMR spectrum of TBCA in solid-phase (Fig. S2 in
Supplementary data) shows a signal in d 151.79 ppm, while the 13C
NMR of TBCA in 98% H2SO4 (Fig. S3 in Supplementary data) dis-
plays two signals (d 147.13 and 146.18 ppm) referring to two dif-
ferent carbonyl groups—see Supplementary material. Comparing
these chemical shifts with the calculated ones at GIAO/B3LYP/6-
311++G**//B3LYP/6-31++G** level (Fig. S4 in Supplementary data)
for the polyprotonated species of TBCA, it is possible to note that
they probably refer to the monoprotonated species. Thus, probably
there is a higher concentration of monoprotonated species in this
media. However, the de facto reacting species could either be
any of the polyprotonated species, with the species with higher
protonation degree having a stronger electrophilic character.
In conclusion, we have shown that the activation, due to highly
acidic medium, can be used to promote reaction of TBCA with
deactivated arenes affording brominated products in good to excel-
lent yields. DFT calculations at B3LYP/6-31++G** level suggest that
the diprotonated form of TBCA would be responsible for the high
reactivity of TBCA in strong acid medium. The driving force for this
reaction with deactivated aromatics is due to relief of the intramo-
lecular charge–charge repulsion in TBCA.
8. Mendonça, G. F.; Sindra, H. C.; de Almeida, L. S.; Esteves, P. M.; de Mattos, M. C.
S. Tetrahedron Lett. 2009, 50, 473.
9. de Almeida, L. S.; Esteves, P. M.; de Mattos, M. C. S. Synthesis 2006,
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11. Tozetti, S. D. F.; de Almeida, L. S.; Esteves, P. M.; de Mattos, M. C. S. J. Braz. Chem.
Soc. 2007, 18, 675.
12. Zolfigol, M. A.; Niknam, K.; Bagherzadeh, M.; Ghorbani-Choghamarani, A.;
Koukabi, N.; Hajjami, M.; Kolvari, E. J. Chin. Chem. Soc. 2007, 54, 1117.
13. (a) Silva, R. R.; Esteves, P. M.; de Mattos, M. C. S. Tetrahedron Lett. 2007, 48,
8747; (b) de Almeida, L. S.; Esteves, P. M.; de Mattos, M. C. S. Synlett 2007,
1687; (c) de Souza, A. V. A.; Mendonça, G. F.; Bernini, R. B.; de Mattos, M. C. S. J.
Braz. Chem. Soc. 2007, 18, 1575; (d) Mendonça, G. F.; Sanseverino, A. M.; de
Mattos, M. C. S. Synthesis 2003, 45; (e) Wengert, M.; Sanseverino, A. M.; de
Mattos, M. C. S. J. Braz. Chem. Soc. 2002, 13, 700.
14. Typical procedure: 1-Bromo-3,5-dinitrobenzene. To a well stirred solution of m-
dinitrobenzene (2 mmol) in 98% sulfuric acid (4 mL) was added TBCA
(0.74 mmol). The reaction was monitored by HRGC and after 4 h the reaction
medium was poured onto crushed ice (100 g), carefully neutralized with 5%
NaOH followed by addition of 10% Na2SO3 solution (20 mL). The aqueous
solution was extracted with CH2Cl2 and the combined organic layer was dried
(anhydrous Na2SO4). After evaporation of the solvent on a rotatory evaporator,
the product was collected and recrystallized from hexane (79%, mp 74–76 °C,
lit. 77 °C16). dH 8.70 (s, 2H), 8.98 (s, 1H) ppm. dC 117.9, 123.8, 132.0, 148.8. IR
(KBr)
m 3095, 2873, 1808, 1614, 1594, 1346, 1307, 1160, 1072, 1000, 914, 894,
836, 725, 636, 514, 487 cmÀ1. MS (70 eV) m/z 246 (M+), 248 (M++2), 200, 202,
170, 172, 153, 155, 75 (100%), 63.

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L. S. de Almeida et al. / Tetrahedron Letters 50 (2009) 3001–3004
15. Pentabromonitrobenzene. To a well stirred solution of TBCA (1.67 mmol) in 7%
w/w SO3 fuming sulfuric acid was carefully added nitrobenzene (1 mmol). The
reaction medium displayed a reddish color that disappeared within 2 minutes,
forming a white suspension. The work-up was similar to that described above.
After evaporation of the solvent on a rotatory evaporator, the product was
collected and recrystallized from hexane (85%, mp 226–228 °C, lit. 230 °C17). dC
116.4, 129.9, 131.8, 156.4 ppm. IR (KBr) 1548, 1502, 1363, 1321, 1305, 1222,
1168, 1066, 894, 761, 598 cmÀ1
16. Lamm, B. Acta. Chem. Scand. 1962, 16, 767.
17. Gilman, H.; Forthrgill, R. E.; Towne, E. B. J. Am. Chem. Soc. 1930, 52, 405.
m
.