Mild and regioselective bromination of aromatic compounds with N,N,N′,N′-Tetrabromobenzene-1,3-disulfonylamide and poly(N-bromobenzene-1,3-disulfonylamide)

Article abstract of DOI:10.1055/s-2005-861851

N,N,N′,N′-Tetrabromobenzene-1,3-disulfonylamide (TBBDA) and poly[N-bromobenzene-1,3-disulfonylamide] (PBBS) can be used for the regioselective bromination of aromatic compounds in excellent yields under mild conditions.

Full text of DOI:10.1055/s-2005-861851

PAPER
1099
Mild and Regioselective Bromination of Aromatic Compounds with N,N,N¢,N¢-
Tetrabromobenzene-1,3-disulfonylamide and Poly(N-bromobenzene-1,3-di-
sulfonylamide)
M
ildand Regiose
a
lective Bro
m
mination of
A
rom
a
i
tic Com
n
pounds Ghorbani-Vaghei,* Hamid Jalili
Department of Chemistry, Faculty of Science, Bu-Ali Sina University, Hamadan, Iran
E-mail: ghorbani@basu.ac.ir
Received 15 November 2004; revised 10 January 2005
We now report a highly para-selective and convenient
method for the bromination of aromatic compounds using
the new reagents TBBDA (2) and PBBS (4) (Figure 1).
Abstract: N,N,N¢,N¢-Tetrabromobenzene-1,3-disulfonylamide
(TBBDA) and poly[N-bromobenzene-1,3-disulfonylamide]
(PBBS) can be used for the regioselective bromination of aromatic
compounds in excellent yields under mild conditions.
The advantages of TBBDA and PBBS are as follows:
1. The preparation of TBBDA and PBBS is easy.
Keywords: bromination, aromatic compounds, TBBDA, PBBS
2. TBBDA and PBBS are stable for three to four months
under normal conditions.
Halogenated aromatic compounds are a useful class of in-
termediates as they are precursors to a number of organo-
metallic species useful in the synthesis of natural products
and pharmaceutically important compounds. The manu-
facture of a range of bulk and fine chemicals, including
flame retardants, disinfectants, antibacterial, and antiviral
drugs, involve bromination.1
3. After the reaction of TBBDA or PBBS with a substrate,
the sulfonamide is recovered and can be reused many
times without decreasing the yield.
4. The reagents are selective (para position).
5. If other functional groups are present in the aromatic
ring of substrates, they do not react with these reagents
(e.g. aldehyde groups attached to the substrate ring are not
oxidized by these reagents whereas Br2 oxidizes this
group).
The introduction of halogens into aromatics rings by elec-
trophilic substitution is an important synthetic procedure.
Chlorine and bromine are reactive toward aromatic hydro-
carbons, but Lewis acid catalysts are normally used to
achieve desirable rates.2,3 Some of the reagents reported
for bromination4–8 are often hazardous, very toxic, expen-
sive, not readily available, they need to be freshly pre-
pared, the reactions require drastic conditions or
prolonged reaction times,4,5 and tedious work-up. Thus, a
milder, selective, non-hazardous, and inexpensive reagent
is still in demand.
The reaction of aromatic compounds 5 with TBBDA and
PBBS in dichloromethane under mild conditions afforded
4-bromo-substituted benzene 6 without side products
(Scheme 1).
The results of the bromination of representative aromatic
compounds are presented in Table 1.
NH2
H2N
Br2N
NBr2
S
O
S
O
S
S
O
O
O
O
O
O
1
2
TBBDA
Br
N
Br
H
H
N
N
N
O
S
S
)
CH2
CH2
S
S
O
)
CH2
CH2
n
n
O
O
O
O
O
O
3
PBBS
4
Figure 1
SYNTHESIS 2005, No. 7, pp 1099–1102
x
x
.
x
x
.2
0
0
5
Advanced online publication: 09.03.2005
DOI: 10.1055/s-2005-861851; Art ID: Z21504SS
© Georg Thieme Verlag Stuttgart · New York

1100
R. Ghorbani-Vaghei, H. Jalili
PAPER
R
lective bromination using our reagents did not require a
catalyst and the aromatic compounds were obtained in
high yields.
R
2 or 4
or
+
1
3
in CH2Cl2
In conclusion, we have synthesized the novel reagents
N,N,N¢,N¢-tetrabromobenzene-1,3-disulfonylamide
(TBBDA) and poly[N-bromobenzene-1,3-disulfonyl-
amide] (PBBS), that are able to brominate aromatic rings
containing ortho,para directing group almost entirely in
the para position.
Br
5
6
Scheme 1
The products 6 were isolated simply by filtering off the
sulfonamide and evaporating the solvent from the filtrate.
The method has advantages in terms of yields, simplicity
of reaction conditions, short reaction times, and lack of
side products. The recovered starting material 1 and 3, can
be rebrominated and used many times without reducing
the yield.
IR and NMR spectra were recorded using a Shimadzu 435-U-04
spectrophotometer (KBr pellets) and a 90 MHz Jeol FT-NMR spec-
trometer, respectively.
Benzene-1,3-disulfonylamide
PCl5 (16.5 mmol), as chlorination agent, was added to the sodium
salt of benzene-1,3-disulfonic acid (5.00 g, 18 mmol). To initiate
the reaction, the vessel was heated (40–50 °C), then the reaction
continues autonomously. After complete conversion (2 h), crushed
ice (100 g) and CHCl3 (100 mL) was added and the organic layer
was separated. Aq NH3 (25%, 400 mL) was added to the solution
while stirring with a mechanical stirrer. After complete addition, re-
moval of the solvent under reduced pressure gave the crude product.
Crystallization from EtOH gave the title compound.
The advantages of our reagents over common reagents in
the bromination of anisole, o-cresol and acetanilide are
shown in Table 2. It is noteworthy that most of these re-
agents such as NBS require the use of a catalyst or ionic
liquid to enhance the reactivity of the reagent, control the
regioselectivity, or improve the yield. However, regiose-
Table 1 Bromination of Aromatic Compounds with TBBDA and PBBS
Entry
Substrate
Producta
Method
Time (min) para (%)
Temp (°C) Yield (%)
1
2
3
4
5
Anthracene
9-Bromoanthracene
9-Bromoanthracene
4-Bromo-N,N-dimethylaniline
4-Bromo-N,N-dimethylaniline
A
B
A
B
A
35
240
30
–
25
40
25
40
25
98
96
95
92
91
Anthracene
–
N,N-Dimethylaniline
N,N-Dimethylaniline
100
100
–
120
40
4-(Dimethylamino)
2-Bromo-4-(dimethylamino)
benzaldehyde
benzaldehyde
6
4-(Dimethylamino)
2-Bromo-4-(dimethylamino)
B
120
–
40
85
benzaldehyde
benzaldehyde
7
8
9
Anisole
4-Bromoanisole
4-Bromoanisole
A
B
A
30
150
65
100
100
–
25
40
25
96
92
86
Anisole
2-Methoxybenzaldehyde
5-Bromo-2-methoxy-
benzaldehyde
10
2-Methoxybenzaldehyde
5-Bromo-2-methoxy-
benzaldehyde
B
90
–
40
89
11
12
13
14
15
16
o-Cresol
4-Bromo-o-cresol
A
B
A
B
A
B
50
25
–
25
25
40
40
25
40
87
o-Cresol
4-Bromo-o-cresol
–
97
N,N-Diethylaniline
N,N-Diethylaniline
Acetanilide
4-Bromo-N,N-diethylaniline
4-Bromo-N,N-diethylaniline
4-Bromoacetanilide
120
180
75
100
100
100
100
79
92.5
83
Acetanilide
4-Bromoacetanilide
120
90
a Products were characterized by their physical properties, comparison with authentic samples, and by spectroscopic methods.
Synthesis 2005, No. 7, 1099–1102 © Thieme Stuttgart · New York

PAPER
Mild and Regioselective Bromination of Aromatic Compounds
1101
1H NMR (DMSO-d6): d = 8.5–8.1 (br, Ar), 7.5 (NH), 3-2.5 (br, ali-
phatic).
Table 2 Reaction Times and Yields for Previously Published Meth-
ods
Substrate
Conditions
Reaction Time Yield
(%)
Poly(N-bromobenzene-1,3-disulfonylamide)
Poly(benzene-1,3-disulfonylamide) (1.00 g, 0.7 mmol) was dis-
solved in chilled aq NaOH (2 mL, 3 M) at r.t. and the solution trans-
ferred to a beaker. Br2 (58.4 mmol) was added to the solution with
vigorous stirring and a precipitate was formed immediately. The
product was collected by vacuum filtration, washed with distilled
cold water (30 mL), and then dried in a vacuum desiccator at r.t. for
4 h.
Anisole
Anisole
Anisole
Anisole
CHCl3, 15–20 °C
24 h
20 h
5 h
909
Silica gel, CCl4, 30 °C
HZSM-5,a CCl4, reflux
9010
7011
765
TBHP (1.0 equiv), HBr
(1.0 equiv)
5 min
Yield: 0.80 g (80%); mp 191–195 °C.
IR (KBr): 1601, 1332, 1154 cm–1.
1H NMR (DMSO-d6): d = 8.5–8.1 (br, Ar), 3–2.5 ppm (br, aliphat-
ic).
Anisole
Anisole
NBS, HCl
1 min
9812
9513
Br2, Fe(NO3)3·1.5N2O4/
charcoal
0.18 min
Bromination of Aromatic Compounds with TBBDA (Method
A)
Anisole
NBS, PTZb
1.5 h
9814
8715
9616
N,N,N¢,N¢-Tetrabromobenzene-1,3-disulfonylamide (0.50 g, 0.90
mmol) and CH2Cl2 (10 mL) were placed in a 25 mL flask. The flask
was cooled in ice-water and anisole (0.10 g, 0.90 mmol) was added
dropwise with stirring. The mixture was stirred for 30 min. at r.t
while the progress of the reaction was monitored by TLC (CCl4–ac-
etone, 9:1). Once the reaction was complete the flask was cooled,
the sulfonamide 1 was filtered off under vacuum filtration, CH2Cl2
was removed under reduced pressure, and the 4-bromoanisole was
collected as a single product; yield: 96%.
o-Cresol
NBS, HBF4·Et2O
6 h
Acetanilide NBS, [bbim]BF4
5–45 min
a HZSM-5 = silica gel/alumina.
b PTZ = phosphotungstic acid on zirconia.
Yield: 90%; mp 228–230 °C.
IR (KBr): 3320, 3090, 1600, 1320, 1130 cm–1.
1H NMR (acetone-d6): d = 6.7 (s, 4 H), 7.7 (t, 1 H), 8.1 (d, 2 H), 8.3
(s, 1 H).
Bromination of Aromatic Compounds with PBBS (Method B)
Poly(N-bromobenzene-1,3-disulfonylamide) (0.50 g) and CH2Cl2
(10 mL) were placed in a 25 mL flask. The flask was cooled in ice-
water and anisole (0.10 g, 0.90 mmol) was added dropwise with stir-
ring. The mixture was refluxed for 150 min. The reaction was mon-
itored by TLC (CCl4–acetone, 9:1). Then the flask was cooled, the
polysulfonamide 3 was removed by vacuum filtration, CH2Cl2 was
removed under reduced pressure, and the 4-bromoanisole was col-
lected as a single product; yield: 92%.
13C NMR (acetone-d6): d = 124.2, 130.6, 129.8, 124.2.
N,N,N¢,N¢-Tetrabromobenzene-1,3-disulfonylamide (TBBDA)
Benzene-1,3-disulfonylamide (3.0 mmol) was dissolved in chilled
aq NaOH solution (3 M, 2 mL) at r.t. and the solution was trans-
ferred to a beaker. Br2 (58.4 mmol) was added to the solution with
vigorous stirring and a precipitate was formed immediately. The
product was collected by vacuum filtration, washed with distilled
cold water (30 mL), and dried in a vacuum desiccator at r.t. for 6 h.
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salt of benzene-1,3-disulfonic acid (5.00 g, 18 mmol). To initiate
the reaction, the vessel was heated (40–50 °C), then the reaction
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heated (80 °C) and stirred for 30 minutes then cooled and water (50
mL) was added. The product was collected by vacuum filtration and
washed with a little cold water (10 mL). Recrystallization from ac-
etone gave the title compound.
Yield: 2.8 g (74%); mp 220–225 °C.
IR (KBr): 3565, 1601, 1332, 1154 cm–1.
Synthesis 2005, No. 7, 1099–1102 © Thieme Stuttgart · New York

1102
R. Ghorbani-Vaghei, H. Jalili
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Synthesis 2005, No. 7, 1099–1102 © Thieme Stuttgart · New York