Simple and improved regioselective brominations of aromatic compounds using N-benzyl-N,N-dimethylanilinium peroxodisulfate in the presence of potassium bromide under mild reactions conditions

Article abstract of DOI:10.2298/JSC100212058G

A simple, efficient, and mild method for the selective bromination of some activated aromatic compounds using N-benzyl-N,N-dimethylanilinium peroxodisulfate in the presence of potassium bromide in non-aqueous solution is reported. The results obtained revealed good to excellent selectivity between the ortho and para positions of phenols and methoxyarenes.

Full text of DOI:10.2298/JSC100212058G

J. Serb. Chem. Soc. 76 (5) 685–692 (2011)
JSCS–4149
UDC 66.094.414+547.52+547.323+
546.32+547.53+547.551.1
Original scientific paper
Simple and improved regioselective brominations of aromatic
compounds using N-benzyl-N,N-dimethylanilinium
peroxodisulfate in the presence of potassium bromide
under mild reactions conditions
1
2
*
HASSAN GHASEMNEJAD-BOSRA , FARHAD RAMZANIAN-LEHMALI
and SOMAYE JAFARI1
1Islamic Azad University – Babol Branch, School of Science, P.O. Box 755, Babol and
2University of Payamenoor, Babol, Iran
(Received 16 March, revised 9 December 2010)
Abstract: A simple, efficient, and mild method for the selective bromination of
some activated aromatic compounds using N-benzyl-N,N-dimethylanilinium
peroxodisulfate in the presence of potassium bromide in non-aqueous solution
is reported. The results obtained revealed good to excellent selectivity between
the ortho and para positions of phenols and methoxyarenes.
Keyword: bromination; N-benzyl-N,N-dimethylanilinium peroxodisulfate; po-
tassium bromide; phenols; methoxyarenes.
INTRODUCTION
Selective bromination of aromatic compounds is an important reaction in
organic synthesis. Therefore, various methods have been developed for the bro-
mination of aromatic rings using different reaction conditions. Direct treatment
of aromatic compounds with molecular bromine normally results in a mixture of
mono-, di-, and polysubstituted products. In addition, direct bromination of acti-
vated aromatic compounds by bromine generates hydrogen bromide, which is
1–4
corrosive, toxic, and pollutes the environment. To overcome these difficulties,
numerous methods have been proposed to increase the selectivity and also the
5–14
yields of the desired para-products.
In recent years, several peroxodisulfate reagents for oxidative transforma-
15
tions under non-aqueous conditions have been reported. As a part of a program
related to the development of peroxodisulfate reagents, a new, simple, and ge-
neral procedure is reported now for the bromination of a number of phenols and
methoxyarenes using N-benzyl-N,N-dimethylanilinium peroxodisulfate
*Corresponding author. E-mail: h_ghasem2000@yahoo.com
doi: 10.2298/JSC100212058G
685
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GHASEMNEJAD-BOSRA, RAMZANIAN-LEHMALI and JAFARI
(DMBAPODS) in the presence of potassium bromide as the source of bromine.
14
N-benzyl-N,N-dimethylanilinium peroxodisulfate was obtained as follows: an
aqueous solution of N-benzyl-N,N-dimethylanilinium bromide was added under
stirring to a solution of potassium peroxodisulfate in water at room temperature.
The products were successively washed with water and acetone and dried under
reduced pressure. This reagent is a stable white powder which could be stored for
months without losing its activity (Scheme 1).
-
Br
N
N
+
+
H2O / rt
2-
2
K2S2O8
+
S2O8
+ 2KBr
n
2
DMBAPODS
Scheme 1. Synthesis of N-benzyl-N,N-dimethylanilinium peroxodisulfate.
EXPERIMENTAL
The reactions were monitored by TLC using silica gel plates and the products purified by
flash column chromatography on silica gel (Merck; 230–400 mesh). The products were iden-
tified by comparison of their spectra and physical data with those of authentic samples. The
1H-NMR spectra of the brominated compounds were measured at 90 MHz on a JEOL spectro-
meter with tetramethylsilane as the internal reference and CDCl3 as the solvent. Elemental
analysis was performed on a LECO 250 instrument.
Typical procedure for the synthesis of N-benzyl-N,N-dimethylanilinium peroxodisulfate
To an aqueous solution of 14.60 g N,N-dimethylanilinium bromide (50 mmol) in 100 mL
H2O was added a solution of 13.51 g potassium peroxodisulfate (50 mmol) in 100 mL H2O.
The mixture was stirred at room temperature for 30 min. The formed precipitate was filtered,
washed with cooled distilled water (50 mL), and dried in a desiccator under vacuum over
calcium chloride to afford a white powder (92 %), which decomposes at 181–183 °C to a dark
brown material. Anal. Calcd. for: C30H36N2O8S2: C, 58.43; H, 5.87; N, 4.54 %. Found: C,
58.46; H, 5.89; N, 4.56; 1H-NMR (90 MHz, DMSO-d6, δ / ppm): 6.9–8.2 (10H, m, C6H5), 5.8
(2H, s. CH2), 3.95 (6H, s. CH3).
Typical procedure for the bromination of aromatic compounds with potassium bromide in the
presence of N-benzyl-N,N-dimethylanilinium peroxodisulfate
To a solution of aromatic compound (1 mmol) in acetonitrile (5 mL), KBr (1.2 mmol)
and N-benzyl-N,N-dimethylanilinium peroxodisulfate (1–1.2 mmol) were added and the mix-
ture heated under reflux for 1.5–9.5 h. The progress of the reaction was monitored by TLC
(eluent: carbon tetrachloride/diethyl ether, 4:2, and carbon tetrachloride/n-hexane, 8:2) or GC
(capillary column). The reaction mixture was cooled to room temperature and filtered. The
excess bromine was removed from the filtrate by the dropwise addition of a sodium thio-
sulfate solution (1 M). Then dichloromethane (5 mL) was added and the solution transferred
to a separatory funnel. The organic layer was separated and dried over magnesium sulfate or
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REGIOSELECTIVE BROMINATION OF AROMATIC COMPOUNDS
687
calcium chloride. Evaporation of the solvent followed by recrystallization or column chroma-
tography on silica gel of the crude product gave the corresponding brominated compounds in
good to excellent yields.
The products were characterized based on their physical and spectral analysis and by
direct comparison with literature data (Supplementary Material).16
RESULTS AND DISCUSION
This article reports the use of potassium bromide as the source of bromine
and N-benzyl-N,N-dimethylanilinium peroxodisulfate as the oxidizing agent in
acetonitrile as solvent for the bromination of a number of phenols and metho-
xyarenes (Scheme 2). The results are given in Table I.
R2
R2
DMBAPODS / KBr
CH3CN / reflux
R1
R1
Br
R3
R3
R1, R2, R3 = H, OH, OMe, Cl, NO2, CH3, COOH
R4
R4
DMBAPODS / KBr
Br
CH3CN / reflux
R4 = OH, OMe
Scheme 2. General reaction for the bromination of aromatic compounds.
Thus, the methoxybenzenes were successfully reacted to afford the desired
monobrominated products (Table I, entries 1–9), except 2-methoxynaphthalene,
which gave 1-bromo-2-methoxynaphthalene (Table I, entry 7). Catechol, phenol,
ortho-cholorophenol, ortho-cresol and ortho-methoxyphenol were quantitatively
converted to the para-brominated products with respect to the hydroxyl groups
(Table I, entries 10–14). para-Nitrophenol and 2,4-dinitrophenol were also con-
verted to the monobrominated products over longer reaction times (Table I, en-
tries 15 and 16). Resorcinol and para-methoxyphenol were quantitatively reacted
to give the corresponding monobrominated products (Table I, entries 17 and 18).
Some other aromatic compounds, such as 1-naphthol and 2-naphthol, were also
subjected to these reaction conditions, and the corresponding products were ob-
tained in good yields (Table I, entries 20 and 21). Salicylic acid and 2,4-dihyd-
roxybezoic acid produced the brominated products over longer times and in low-
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GHASEMNEJAD-BOSRA, RAMZANIAN-LEHMALI and JAFARI
er yields compared to the other activated phenols and methoxyarenes (Table I,
entries 19 and 22).
TABLE I. Bromination of some aromatic compounds with potassium bromide in the presence
of N-benzyl-N,N-dimethylanilinium peroxodisulfate (reactions were performed in CH3CN at
reflux temperature)
Oxidant/sub Time Yield M.p. M.p.lit.
Entry
Substrate
Product(s)a
b
-strate/KBr
h
%
°C
°C
1
1.2/1/1.2
3
91
Liq Liq18e
Br
Br
OMe
OMe
2
3
4
1.2/1/1.2
1.2/1/1.2
1.2/1/1.2
3.5
4
95
69
25
55
69–
7018a
OMe
OMe
OMe
Me
Me
93
94
25–
2618a
Br
OMe
MeO
MeO
Br
3
54–
5518a
MeO
OMe
OMe
OMe
OMe
OMe
OMe
MeO
Br
OMe
OMe
OMe
5
6
1/1/1.2
1/1/1.2
2.5
7
92
84
Liq Liq18a
OMe
OMe
OMe
64
55
63–
6518a
Br
Br
7
8
1.2/1/1.2
1/1/1.2
6
5
90
89
53–
OMe
5618a
OMe
Liq Liq18a
OMe
Cl
OMe
Cl
Br
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REGIOSELECTIVE BROMINATION OF AROMATIC COMPOUNDS
689
TABLE I. Continued
Oxidant/sub Time Yield M.p. M.p.lit.
Entry
Substrate
Product(s)a
b
-strate/KBr
h
%
°C
°C
OMe
OMe
9
1/1/1.2
3.5
96
152
152–
–15418a
OH
Br
OH
OH
10
1.2/1/1.2
3
95
87 87–8918b
OH
Br
OH
OH
11
12
1/1/1.2
1/1/1.2
4.5
1.5
96
97
63 61–6418b
51 49–5018c
OH
OH
Br
Br
OH
OH
Cl
Cl
13
1/1/1.2
4
93
57 58–5918d
34 34–3718c
OH
Br
Br
OH
CH3
CH3
14
15
16
1/1/1.2
1/1/1.2
1/1/1.2
3.5
8
96
97
91
OH
OMe
OH
OMe
OH
112
111–
–11518a
O2N
O2N
O2N
O2N
OH
Br
Br
9.5
99 97–9918a
OH
OH
NO2
NO2
17
18
1/1/1.2
1/1/1.2
2
94
95
104
103–
–10518d
OH
Br
OH
OH
OH
4.5
45 44–4518d
MeO
OH
MeO
OH
Br
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GHASEMNEJAD-BOSRA, RAMZANIAN-LEHMALI and JAFARI
TABLE I. Continued
Oxidant/sub Time Yield M.p. M.p.lit.
Entry
Substrate
Product(s)a
b
-strate/KBr
h
%
°C
°C
19
1/1/1.2
6
79
60 58–6218a
OH
CO2H
Br
OH
CO2H
Br
20
21
1/1/1.2
1/1/1.2
5.5
5
90
79 78–8118a
OH
OH
OH
91
73
129
165
129–
OH
–13118a
Br
22
Br
1/1/1.2
6
165–
–16718a
OH
CO2H
OH
CO2H
OH
OH
a
1
All products were characterized spectroscopically ( H-NMR and IR) and showed physical and spectral data in
16 b
accordance with their expected structure and by comparison with authentic samples;
products
yields of isolated
Although the mechanism for the bromination with lithium bromide and
N-benzyl-N,N-dimethylanilinium peroxodisulfate is not clear, the reaction ap-
pears to be initiated via the formation of the N-benzyl-N,N-dimethylanilinium
sulfate radical A by homolysis of N-benzyl-N,N-dimethylanilinium peroxodisul-
17
fate. The sulfate radical A may oxidize the bromide anion to the bromonium
cation. The electrophilic attack of the bromonium cation at the p-position of ac-
tivated aromatic compounds produces the intermediate B, which is readily con-
verted to the brominated product. However, there is an alternative possibility to
18
form the radical cation C by a one-electron transfer, which may convert to the
4
radical intermediate D (Scheme 3).
It is worth mentioning that the chemoselective conversion of methoxyaroma-
tics to their para-substituted products was achieved in excellent yield. Another
noteworthy advantage of this system lies in its ability to selectively brominate the
para vs. the ortho position in catechol, phenol, ortho-chlorophenol, 2-methoxy-
phenol and ortho-cresol.
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REGIOSELECTIVE BROMINATION OF AROMATIC COMPOUNDS
691
O
O
S
-
_
O
.
O
_
O
Br
_
+
DMBAPODS
2
Br
Ph
N
2
Ph
+
N
+
S
O
+
Ph
Ph
O
O
A
MeO
MeO
MeO
Br
+
H
+
Br
H
+
OMe
OMe
OMe
+
Br
B
-e
or A
H
MeO
MeO
MeO
-
H
A
-e
H
Br
+.
OMe
.
OMe
+
OMe
Br
Br
D
C
Scheme 3. Proposed mechanism for the synthesis of brominations of aromatic compounds.
CONCLUSIONS
The presented method represents an efficient, chemoselective and environ-
mentally friendly synthesis methodology for the bromination of some activated
aromatic compounds.
SUPPLEMENTARY MATERIAL
1
The H-NMR and 13C-NMR spectral data of the products are available electronically at
http://www.shd.org.rs/JSCS/, or from the corresponding author on request.
Acknowledgements. We are thankful to the Payamenoor University Research Councils
and also the Islamic Azad University – Babol Branch, Babol, Iran for their partial support of
this work.
И З В О Д
РЕГИОСЕЛЕКТИВНО БРОМОВАЊЕ АРОМАТИЧНИХ ЈЕДИЊЕЊА ПОМОЋУ
N-БЕНЗИЛ-N,N-ДИМЕТИЛАНИЛИНИЈУМ-ПЕРОКСОДИСУЛФАТА У ПРИСУСТВУ
КАЛИЈУМ-БРОМИДА ПОД БЛАГИМ РЕАКЦИОНИМ УСЛОВИМА
HASSAN GHASEMNEJAD-BOSRA1, FARHAD RAMZANIAN-LEHMALI2 и SOMAYE JAFARI1
1Islamic Azad University-Babol Branch, School of Science, P.O. Box 755, Babol и
2University of Payamenoor, Babol, Iran
Описан је једноставан и ефикасан поступак селективног бромовања активираних аро-
матичних једињења помоћу N-бензил-N,N-диметиланилинијум-пероксодисулфата у при-
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692
GHASEMNEJAD-BOSRA, RAMZANIAN-LEHMALI and JAFARI
суству калијум-бромида у неводеним растварачима. Постигнута је добра селективност
између orto i para супституције фенола и метоксиарена.
(Примљено 16. марта, ревидирано 9. децембра 2010)
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