Tribromoisocyanuric acid: A new reagent for regioselective cobromination of alkenes

Article abstract of DOI:10.1055/s-2006-941601

A simple one-step method for the preparation of tribromoisocyanuric acid in good yield (87%) has been developed. The reaction of tribromoisocyanuric acid with alkenes in presence of nucleophilic solvents (MeOH, i-PrOH, AcOH and a mixture of H₂O-acetone, 1:5) led to the corresponding β-bromoethers, β-bromoacetates and bromohydrins, in high regioselectivity and good yields (73-98%). Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-941601

LETTER
1515
Tribromoisocyanuric Acid: A New Reagent for Regioselective Cobromination
of Alkenes
A
N
ew Reagent
e
f
or Regios
o
elective Cob
n
romination o
a
f
A
lkenes rdo 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; pesteves@iq.ufrj.br
Received 21 November 2006
One of the great advantages of using TBCA for the bromi-
Abstract: A simple one-step method for the preparation of tri-
nation of organic compounds is that one mole of TBCA
can transfer three moles of bromine atom to the substrate.
A good example of the efficiency of TBCA in brominat-
bromoisocyanuric acid in good yield (87%) has been developed.
The reaction of tribromoisocyanuric acid with alkenes in presence
of nucleophilic solvents (MeOH, i-PrOH, AcOH and a mixture of
H2O–acetone, 1:5) led to the corresponding b-bromoethers, b-bro- ing reactions was reported by our group on the bromina-
moacetates and bromohydrins, in high regioselectivity and good
tion of activated aromatic rings, in which each mole of
TBCA brominates three moles of the substrate.9
yields (73–98%).
Key words: alkenes, cohalogenation, Oxone®, tribromoisocyanu-
ric acid
Cl
N
Br
N
H
N
O
O
O
O
O
O
N
N
N
N
N
N
Cl
Cl
Br
Br
Br
Br
N-Haloimides are useful reagents for the halogenation of
organic compounds,1 once in this kind of compounds the
halogen has a greater electrophilic character than in X2.
They are also easy to manipulate and produce the corre-
sponding imides as by-products, which are less toxic and
corrosive than HX (X = Cl, Br, I), generated when ele-
mentary halogen is used.2 The cohalogenation of alkenes
(halogenation in the presence of a nucleophilic solvent)3
is an important transformation in organic chemistry, once
b-haloethers, b-haloesters and halohydrins are useful
intermediates in organic synthesis. N-halosaccharines
(NXSac), were found to be good reagents for the synthesis
of this kind of compounds1b and their preparations are
described in the literature in good yields.4
O
O
O
TCCA
TBCA
DBCA
Figure 1 Haloisocyanuric acids
In the present work, we report a new method for the prep-
aration of TBCA and also its application in regioselective
cobromination of alkenes with oxygenated nucleophiles.
In a previous study, Gottardi10 demonstrated that the reac-
tion between cyanuric acid alkali salts and Br2 produces a
mixture of di- and trisubstituted products, which is very
difficult to separate, because they are insoluble in most
solvents. Recently, it has been reported that N-chloro- and
N-bromosaccharine can be prepared from sodium saccha-
rinate and a potassium halide in presence of Oxone®.4
This is an efficient and safe methodology from the ‘green
chemistry’ point of view.
Recent papers have demonstrated that trichloroisocyanu-
ric acid (TCCA, Figure 1) is not only a good oxidant5 but
also an efficient halogenating agent, due to its capability
of transferring a chlorine atom to unsaturated substrates in
electrophilic reactions.6 The tribromoisocyanuric (TBCA)
and dibromoisocyanuric acids (DBCA, Figure 1), ana-
logues of TCCA, were first prepared by Gottardi7 employ-
ing an expensive silver salt in a tedious methodology
where silver cyanurate reacts with gaseous bromine at 130
°C to form the product along with AgBr. Both product and
AgBr are insoluble in most solvents, making their separa-
tion from the reaction mixture difficult. The application of
DBCA in brominating reactions has already been report-
ed, especially in electrophilic bromination of aromatic
rings.8 Recently, our group has reported the use of TBCA
for the regioselective bromination of activated aromatic
rings.9 However, the bromination of alkenes using TBCA
has not been reported yet.
Hence, TBCA was prepared in analogy of NXSac prepa-
ration method.4 The product was obtained in 87% after 24
hours by the reaction of an aqueous solution of Oxone®
with sodium cyanurate in the presence of KBr
(Equation 1). The product, a white stable solid, was easily
isolated by vacuum filtration, with no need of further pu-
rification and was characterized by FT-IR and CP-MAS
13C NMR.11 Our methodology proved to be simpler and
considerably less expensive than the preparation proposed
by Gottardi.7
O
OH
1) NaOH, Na2CO3, KBr; H2O
2) Oxone®, 24 h, r.t.
Br
Br
N
N
N
N
O
N
O
HO
N
OH
Br
87 %
SYNLETT 2006, No. 10, pp 1515–1518
2
1
.0
6
.2
0
0
6
Advanced online publication: 12.06.2006
DOI: 10.1055/s-2006-941601; Art ID: S11505ST
© Georg Thieme Verlag Stuttgart · New York
Equation 1

1516
L. S. de Almeida et al.
LETTER
Table 1 Cobromination of Alkenes
O
Br
Br
OR
Br
N
N
+
O
N
O
Br
Entry
1
Alkene
Product
Reaction conditions
Yield (%)a
OH
Acetone–H2O (5:1), 5 min
9112
9013
7814
8715
Br
O
2
3
4
5
Me
MeOH, 60 min
i-PrOH, 60 min
AcOH, 60 min
Br
O
Br
O
O
Br
Acetone–H2O (5:1), 10 min
Acetone–H2O (5:1), 60 min
9816
8017
OH
Br
6
7
OH
Br
Me
O
MeOH, 150 min
8018
Br
8
9
O
i-PrOH, 150 min
8019
Br
O
O
AcOH, 150 min
7520
Br
10
OH
Acetone–H2O (5:1), 30 min
Acetone–H2O (5:1), 120 min
7821
8122
Br
Br
11
12
Br
OH
OH
+
Hex
Hex
Hex
Hex
Hex
(70:30)b
CH3
Br
O
+
7323
O
MeOH, 120 min
Br
CH3
Hex
(70:30)b
a Isolated based on the alkene.
b Determined by HRGC.
Synlett 2006, No. 10, 1515–1518 © Thieme Stuttgart · New York

LETTER
A New Reagent for Regioselective Cobromination of Alkenes
1517
In order to develop a new methodology of cobromination
of alkenes, we applied TBCA as source of Br+ in the pres-
ence of oxygenated nucleophiles. In this study it was used
cyclohexene, 1-methylcyclohexene, styrene, and a-meth-
ylstyrene as substrates and water, methanol, isopropanol
and acetic acid as nucleophilic solvents.
Acknowledgment
The authors thank CAPES, CNPq and FAPERJ for the financial
support.
References and Notes
(1) (a) Duan, S.; Turk, J.; Speigle, J.; Corbin, J.; Baker, R. J. J.
Org. Chem. 2000, 65, 3005. (b) De Souza, S. P. L.; Da
Silva, J. F. M.; De Mattos, M. C. S. J. Braz. Chem. Soc.
2003, 14, 832; available at http://jbcs.sbq.org.br.
(2) De La Mare, P. B. Electrophilic Halogenation; Cambridge
University Press: Cambridge, 1976, Chap. 5 and 7.
(3) (a) Da Silva, F. M.; Jones, J. Jr.; De Mattos, M. C. S. Curr.
Org. Synth. 2005, 2, 393. (b) Sanseverino, A. M.; Da Silva,
F. M.; Jones, J. Jr.; De Mattos, M. C. S. Quim. Nova 2001,
24, 637; available at http://www.quimicanova.sbq.org.br/
quimicanova.htm. (c) Rodriguez, J.; Dulcère, J.-P. Synthesis
1993, 1177.
(4) De Souza, S. P. L.; Da Silva, J. F. M.; De Mattos, M. C. S.
Synth. Commun. 2003, 33, 935.
(5) (a) Tilstam, U.; Weinmann, H. Org. Process Res. Dev. 2002,
6, 384. (b) Zolfigol, M.; Madrakian, E.; Ghaemi, E.;
Mallakpour, S. Synlett 2002, 1633.
(6) (a) Mendonça, G. F.; Magalhães, R. M.; De Mattos, M. C. S.;
Esteves, P. M. J. Braz. Chem. Soc. 2005, 16, 695; available
at http://jbcs.sbq.org.br. (b) Wengert, M.; Sanseverino, A.
M.; De Mattos, M. C. S. J. Braz. Chem. Soc. 2002, 13, 700;
available at http://jbcs.sbq.org.br. (c) Mendonça, G. F.;
Sanseverino, A. M.; De Mattos, M. C. S. Synthesis 2003, 45.
(7) Gottardi, W. Monatsh. Chem. 1967, 98, 1613.
(8) (a) Malm, J.; Hörnfeldt, A. B.; Gronowitz, S. J. Heterocycl.
Chem. 1994, 31, 521. (b) Gottardi, W. Monatsh. Chem.
1968, 99, 815. (c) Leed, A. R.; Boettger, S. D.; Ganem, B. J.
Org. Chem. 1980, 45, 1098.
(9) De Almeida, L. S.; Esteves, P. M.; De Mattos, M. C. S.
Synthesis 2006, 221.
(10) Gottardi, W. Monatsh. Chem. 1967, 98, 507.
(11) CP-MAS 13C NMR: d = 151.8 (C=O) ppm. FT-IR: n = 1741,
1724, 1660, 1652, 1481, 1404, 1396, 1331, 1196, 1144,
1051, 736, 717 cm–1.
Bromohydrins were rapidly obtained in good yields using
the cited substrates and a mixture of acetone–water (5:1,
Table 1). The regioselectivity was very high forming
products from trans-addition following the Markowni-
koff’s rule and no regioisomers were detected by the ana-
1
lytical procedures employed (GCMS and H NMR and
13C NMR spectroscopy). Exception was observed with 1-
octene that produced a mixture of bromohydrins in which
the secondary alcohol predominated (70:30, by HRGC).
Bromination of cyclohexene and styrene with TBCA
(Table 1) in the presence of alcohols (MeOH and i-PrOH)
and acetic acid resulted on the respective b-bromoethers
and b-bromoacetates, in good yields and high regioselec-
tivity, also forming products from trans-addition follow-
ing the Markownikoff’s rule as did the bromohydrins.
Once more, reaction of 1-octene with TBCA in methanol
produced predominantly 1-bromo-2-methoxyoctane
along with some of its regioisomer (70:30 by HRGC).
In summary, the present work describes a new simple one-
step synthesis of TBCA, using low cost reagents and in a
procedure simpler than Gottardi’s. This reagent proved to
be a very efficient for the cobromination of alkenes. The
reactions of TBCA and alkenes showed very high regio-
selectivity leading to the respective bromohydrins, b-bro-
moethers and b-bromoacetates in good yields and under
mild conditions. These products are useful intermediates
for diverse organic transformations.3
(12) 1H NMR (CDCl3): d = 1.24–1.37 (m, 3 H), 1.67–1.86 (m, 3
H), 2.10–2.20 (m, 1 H), 2.25–2.60 (m, 2 H), 3.50–3.70 (m, 1
H) 3.90 (ddd, 1 H, J1 = 11.68 Hz, J2 = 9.57 Hz, J3 = 4.35 Hz)
ppm. 13C NMR (CDCl3): d = 24.1, 26.6, 33.5, 36.2, 61.8,
75.30 ppm. MS (70 eV): m/z (%) = 180 [M+ + 2], 178 [M+],
99, 81 (100), 57, 41.
Procedure for Preparation of TBCA
To a stirred solution of cyanuric acid (12.5 mmol), NaOH (37.5
mmol), Na2CO3 (18.75 mmol) and KBr (37.5 mmol) in H2O (180
mL) cooled in an ice bath was added dropwise a solution of Oxone®
(37.5 mmol) in H2O (150 mL). A white solid precipitates during the
addition of oxidant solution, forming a dense suspension, which is
stirred for 24 h. The product is isolated by vacuum filtration,
washed with cold H2O and dried over P2O5 needing no further puri-
fication. Yield 87%; mp not determined because it decomposes on
heating.11
(13) 1H NMR (CDCl3): d = 1.20–1.40 (m, 3 H), 1.64–1.88 (m, 3
H), 2.15–2.34 (m, 2 H), 3.17–3.28 (m, 1 H), 3.42 (ddd, 1 H,
J1 = 9.56 Hz, J2 = 8.53 Hz, J3 = 4.44 Hz) ppm. 13C NMR
(CDCl3): d = 23.1, 25.3, 29.9, 35.4, 55.2, 57.1, 83.1 ppm. MS
(70 eV): m/z (%) = 194 [M+ + 2], 192 [M+], 113, 81, 71
(100), 41.
General Procedure for Cobromination of Alkenes
(14) 1H NMR (CDCl3): d = 1.13–1.43 (m, 9 H), 1.62–1.90 (m, 3
H), 2.02–2.11 (m, 1 H), 2.30–2.37 (m, 1 H), 3.33–3.40 (m, 1
H), 3.78 (sept, 1 H, J = 6.15 Hz), 3.90 (ddd, 1 H, J1 = 9.76
Hz, J2 = 8.93 Hz, J3 = 4.43 Hz) ppm. 13C NMR (CDCl3): d =
27.5, 23.0, 23.5, 25.5, 32.5, 35.8, 56.6, 71.2, 79.7 ppm.
MS (70 eV): m/z (%) = 222 [M+ + 2], 220 [M+], 178, 180, 99,
81 (100), 57, 43.
To a stirred solution of the alkene (2 mmol) in the appropriated sol-
vent (12.5 mL of acetone and 2.5 mL of H2O for bromohydrins, or
5 mL of MeOH or i-PrOH or AcOH for b-bromoethers and b-bro-
moacetates), was added TBCA (0.67 mmol) at r.t. in small portions.
After the elapsed time shown in Table 1 (the termination of the re-
action was determined by gas chromatography), CH2Cl2 (10 mL)
and H2O (10 mL) were added, cyanuric acid was filtered off and the
resulting solution was treated with 10% aq Na2SO3 (50 mL). The
aqueous phase was washed with CH2Cl2 (2 × 10 mL) and the com-
bined organic layer was dried over anhyd Na2SO4. After evapora-
tion of the solvent on a rotary evaporator, the product was collected.
(15) 1H NMR (CDCl3): d = 1.27–1.47 (m, 3 H), 1.74–1.96 (m, 3
H), 2.08 (s, 3 H), 2.13 (m, 1 H), 2.32–2.39 (m, 1 H), 3.96
(ddd, 1 H, J1 = 10.45 Hz, J2 = 9.29 Hz, J3 = 4.26 Hz), 4.84–
4.93 (m, 1 H) ppm. 13C NMR (CDCl3): d = 21.0, 23.3, 25.6,
35.7, 52.8, 75.8, 170.0 ppm. MS (70 eV): m/z (%) = 222 [M+
+ 2], 220 [M+], 160, 162, 81, 43 (100).
Synlett 2006, No. 10, 1515–1518 © Thieme Stuttgart · New York

1518
L. S. de Almeida et al.
LETTER
(16) 1H NMR (CDCl3): d = 1.25–1.48 (m, 5 H), 1.68–2.05 (m, 4
H), 2.15 (br s, 1 H), 2.21–2.27 (m, 1 H), 4.15 (dd, 1 H,
J1 = 11.52 Hz, J2 = 4.10 Hz) ppm. 13C NMR (CDCl3): d =
22.8, 23.2, 26.3, 34.7, 38.2, 66.0, 72.5 ppm. MS (70 eV):
m/z (%) = 194 [M+ + 2], 192 [M+], 177, 179, 113, 95, 71
(100), 43.
(20) 1H NMR (CDCl3): d = 2.13 (s, 3 H), 3.54 (m, 2 H), 5.98 (dd,
1 H, J1 = 7.41 Hz, J2 = 5.12 Hz), 7.36 (s, 5 H) ppm. 13C NMR
(CDCl3): d = 20.9, 34.2, 74.8, 126.5, 128.6, 137.6, 169.8
ppm. MS (70 eV): m/z (%) = 244 [M+ + 2], 242 [M+], 162,
121, 120, 103, 77, 43 (100).
(21) 1H NMR (CDCl3): d = 1.68 (s, 3 H), 2.63 (s, 1 H), 3.73 (dd,
2 H, J1 = 12.45 Hz, J2 = 10.20 Hz), 7.25–7.49 (m, 5 H) ppm.
13C NMR (CDCl3): d = 28.0, 46.2, 73.1, 124.8, 127.5, 128.4,
144.2 ppm. MS (70 eV): m/z (%) = 216 [M+ + 2], 214 [M+],
199, 201, 121 (100), 77, 43.
(17) 1H NMR (CDCl3): d = 2.81 (d, 1 H, J = 2.73 Hz) 3.48–3.64
(m, 2 H), 4.89–4.94 (m, 1 H), 7.37 (s, 5 H) ppm. 13C NMR
(CDCl3): d = 40.1, 73.7, 125.9, 128.4, 128.6, 140.3 ppm. MS
(70 eV): m/z (%) = 202 [M+ + 2], 200 [M+], 107 (100), 79,
77, 51.
(22) (a) 1-Bromo-2-octanol: 13C NMR (CDCl3): d = 14.09,
22.62, 25.63, 29.20, 31.76, 35.19, 40.56, 71.16 ppm. MS (70
eV): m/z (%) = 128, 125, 123, 115, 97, 69, 55 (100), 43.
(b) 2-Bromo-1-octanol: 13C NMR (CDCl3): d = 14.09,
22.62, 27.45, 28.72, 31.65, 34.95, 60.12, 67.34 ppm. MS (70
eV): m/z (%) = 137, 135, 111, 69 (100), 55.
(18) 1H NMR (CDCl3): d = 3.31 (s, 3 H), 3.42–3.59 (m, 2 H), 4.39
(dd, 1 H, J1 = 7.86 Hz, J2 = 4.44 Hz), 7.34–7.43 (m, 5 H)
ppm. 13C NMR (CDCl3): d = 36.2, 57.2, 83.4, 126.7, 128.6,
139.0 ppm. MS (70 eV): m/z (%) = 216 [M+ + 2], 214 [M+],
121 (100), 91, 77, 51.
(19) 1H NMR (CDCl3): d = 1.12 (d, 3 H, J = 6.15 Hz), 1.23 (d, 3
H, J = 6.14 Hz), 3.38–3.48 (m, 2 H), 3.57 (sept, 1 H, J = 6.14
Hz), 4.58 (dd, 1 H, J1 = 7.86 Hz, J2 = 4.78 Hz), 7.35 (s, 5 H)
ppm.13C NMR (CDCl3): d = 21.2, 23.1, 37.0, 70.4, 79.3,
126.7, 128.2, 128.5, 140.6 ppm. MS (70 eV): m/z (%) = 185,
183, 149, 107 (100), 79, 43.
(23) (a) 1-Bromo-2-methoxyoctane: 13C NMR (CDCl3): d =
13.99, 22.52, 25.08, 29.21, 31.69, 32.81, 34.53, 57.27, 80.27
ppm. MS (70 eV): m/z (%) = 139, 137, 129, 97, 69, 55 (100),
41.
(b) 2-Bromo-1-methoxyoctane: 13C NMR (CDCl3): d =
13.99, 22.52, 27.16, 28.64, 31.58, 35.26, 53.53, 58.87, 76.93
ppm. MS (70 eV): m/z (%) = 143, 135, 137, 111, 69, 45
(100), 41.
Synlett 2006, No. 10, 1515–1518 © Thieme Stuttgart · New York