Aromatic bromination of aldehydes and ketones using 1,3-di-n- butylimidazolium

Article abstract of DOI:10.1007/BF03249087

An environmentally benign and efficient process for the preparation of monobromo derivatives of aryl aldehydes and ketones was developed by simple and practical reactions of aryl aldehydes or ketones with 1,3-di-n-butylimidazolium tribromide ([BBIm]Br₃), as a brominating reagent under solvent-free conditions in very high yields. The process has several advantages: high conversions, short reaction time, mild reaction conditions, simple workup with good to quantitative yields and re-usable ionic liquid.

Full text of DOI:10.1007/BF03249087

J. Iran. Chem. Soc., Vol. 8, No. 2, June 2011, pp. 531-536.
JOURNAL OF THE
Iranian
Chemical Society
Aromatic Bromination of Aldehydes and Ketones Using 1,3-Di-n-butylimidazolium
Tribromide [BBIm]Br Ionic Liquids under Solvent-Free Conditions
3
S.P. Borikar and T. Daniel*
Division of Organic Chemistry, National Chemical Laboratory, Pune- 411 008, India
(
Received 26 May 2010, Accepted 29 October 2010)
An environmentally benign and efficient process for the preparation of monobromo derivatives of aryl aldehydes and ketones
was developed by simple and practical reactions of aryl aldehydes or ketones with 1,3-di-n-butylimidazolium tribromide
(
[BBIm]Br ), as a brominating reagent under solvent-free conditions in very high yields. The process has several advantages: high
3
conversions, short reaction time, mild reaction conditions, simple workup with good to quantitative yields and re-usable ionic
liquid.
Keywords: Ionic liquid, Bromination, [BBIm]Br , Solvent-free, Green chemistry
3
INTRODUCTION
ipsobromodeformulated product. Bromination of aromatic
compounds using benzyl triethyl ammonium tribromide has
been reported by Pourmousavi et al. [12]. Hajipour et al. have
described the electron-rich aromatic bromination using KBr
and benzyltriphenylphosphonium peroxymonosulfate [13].
Recently, the bromination of aromatic aldehydes catalyzed by
ceric ammonium nitrate and silica gel was reported [14].
However, there exist various limitations with the reported
methodologies such as long reaction times, use of halogenated
solvents, harsh reaction conditions, use of costly catalysts,
some of which yield mass products that cannot be isolated,
and relatively moderate yields. These problems were
overcome to some extent by recently reported regioselective
bromination of anilines and phenols using a novel ionic liquid
1-butyl-3-methylpyridinium tribromide ([BMPy]Br3) and
BBIm]Br3 under solvent-free conditions [15,16]. In recent
years, there has been considerable interest in developing green
chemistry [17] for organic synthesis due to environmental
demand and sustainability. There are various kinds of alkyl
imidazolium salts which are commercially available as room
temperature ionic liquids (RTILs). The combination of
Development of environmentally benign and efficient
processes with simple work-up and high purity of the products
with high yields is currently receiving considerable attention.
In this context, tribromide ionic liquid plays an important role
in the process of obtaining monobromo derivatives with the
ultimate goal of hazard-free, waste-free and solvent-free
efficient synthesis of biologically active compounds that can
be used as precursors of natural products [1,2].
Bromo derivatives of aromatic aldehydes and ketones were
commonly generated from the formulation of brominated
arenes [3] or from the methyl oxidation undergoing several
steps [4]. The direct bromination of aryl aldehydes and
ketones was ordinarily used asa specially brominated reagent
[
5-11]. Bromination of salicylaldehyde has been reported with
good yield of 3,5-dibromosalicylate via pyridinium
hydrobromide perbromide bromination (PHPB) [8].
Unfortunately, it gave dibromo product as well as
*Corresponding author. E-mail: d.thomas@ncl.res.in

Borikar & Daniel
alkylimidazolium cation with the tribromide anion should
molecular bromine stirring and cooling in an ice-bath to
regenerate 1,3-di-n-butylimidazolium tribromide [BBIm]Br
ionic liquid and reused for the subsequent reaction without
loss of activity.
therefore lead to RTIL bromine analog. Ionic liquids were
introduced as alternative green reaction media because of their
unique chemical and physical properties of non-volatility, non-
inflammability, thermal stability, and ease of recyclability.
3
Selected Spectroscopic Data
5-Bromo-4-hydroxy-3-methoxybenzaldehyde (Table 1,
entry 5). White solid; m.p.: 165-167 °C; H NMR (CDCl 200
EXPERIMENTAL
1
3
,
Preparation
Tribromide [BBIm]Br3
In a fume cupboard, molecular bromine (1.956 ml, 0.038
mol) was added dropwise for over 15 min to 1,3-di-n-
butylimidazolium bromide [BBIm]Br (10.0 g, 0.038 mol)
stirring and cooling in an ice-bath affording a deep red liquid
IL 2 with stirring being continued for 2 h. Under reduced
pressure for over 5 h at 60 °C, 15.5 g (96.1%) pure IL 2 was
obtained as a red oil. H NMR (CDCl , 200 MHz): 0.98 (t, 6H,
J = 7.31 Hz), 1.36 (m, 4H), 1.90 (m, 4H), 4.31 (t, 4H, J = 7.52
of
1,3-Di-n-Butylimidazolium
MHz): δ 3.98 (s, 3H), 6.55 (brs, 1H), 7.35 (d, J = 1.4 Hz, 1H),
1
3
7.63 (d, J = 1.4 Hz, 1H), 9.80 (s, 1H); C NMR (CDCl 50
3,
MHz): δ 56.91, 108.34, 108.40, 130.25, 130.36, 147.82,
+
149.01, 189.64; GC-MS (EI), m/z: 230 (M ), 232 (M+2); IR
(CHCl ): 3314, 2976, 2945, 2848, 1685, 1588, 1511, 1429,
3
-1
1358, 1291, 1158, 1055, 682 cm .
6-Bromo-3-hydroxybenzaldehyde (Table 1, entry 6).
1
White solid; m.p.: 130-132 °C; H NMR (CDCl , 200 MHz): δ
3
1
7.02 (d, J = 8.89 Hz, 1H), 7.44-7.50 (m. 2H), 10.32 (s, 1H);
3
1
3
C NMR (CDCl , 50 MHz): δ 114.68, 115.75, 117.61, 123.68,
3
1
3
+
Hz), 7.44 (d, 2H, J = 8.11 Hz), 8.99 (s, 1H); C NMR (CDCl3,
5 MHz): 12.86, 18.82, 31.60, 49.11, 121.92, 135.99; MS
ESI): 181 (M-X ); Anal. Calcd. for C11 : C, 31.38; H,
.03; N, 6.65. Found: C, 31.31; H, 4.93; N, 6.50.
134.90, 155.79, 192.48; GC-MS (EI), m/z : 200 (M ), 202
(M+2); IR (CHCl ): 3505, 1698 cm .
-1
7
(
5
3
3
H21Br
3
N
2
6-Bromo-3-hydroxyacetophenone (Table 1, entry 14).
1
White solid; m.p.: 75-76 °C; H NMR (CDCl3, 200 MHz): δ
1
3
2
.61 (s, 3H), 6.78-6.88 (m, 2H), 7.45 (d, J = 8.86 Hz, 1H); C
General Procedure for the Bromination of Aromatic
Aldehydes and Ketones
NMR (CDCl , 50 MHz): δ 30.19, 108.78, 115.99, 119.45,
3
+
134.76, 142.01, 155.39, 202.69; GC-MS (EI), m/z: 214 (M ),
-1
To a stirred mixture of aromatic aldehydes or ketones (2.5
mmol) was added 1,3-di-n-butylimidazolium tribromide (2.5
mmol) at room temperature. After completion of the reaction
as indicated by TLC, water was added into the reaction
mixture to quench the IL. The resulting reaction mixture was
extracted with diethyl ether, separated from the organic layer,
dried over sodium sulfate and concentrated to afford pure
monobromo aldehydes or monobromo ketones. The yields are
summarized in Table 1. All the compounds were characterized
on the basis of their spectroscopic data and by comparison
with those reported in the literature.
216 (M+2); IR (CHCl ): 3498, 1697 cm .
3
RESULTS AND DISCUSSION
We would like to explain the synthesis, full
characterization, and reactivity of 1,3-di-n-butylimidazolium
tribromide [BBIm]Br , a proton-free RTIL bromine analog.
3
This does not have any measurable vapor pressure and has
been demonstrated for selective nuclear bromination reactions.
The tribromide in question is a stable liquid which was
readily prepared by the addition of molecular bromine to 1,3-
di-n-butylimidazolium bromide [BBIm]Br dropwise under
Regeneration of Ionic Liquids
After the addition of water into the reaction mixture, the
water soluble ionic liquid 1,3-di-n-butylimidazolium bromide
stirring, which exothermally yielded the red liquid [BBIm]Br ,
3
-3
that displayed a density of 1.55 g cm and a viscosity of 59.5
cP (Scheme 1). The excess bromine, absorbed by [BBIm]Br
3
,
[
BBIm]Br was recovered by evaporation of the aqueous
was removed completely under a high vacuum. [BBIm]Br is
3
solution and washing with diethyl ether in each case. The
recovered ionic liquid [BBIm]Br was dried and treated with
hydrophobic, while [BBIm]Br is highly hydrophilic and
hygroscopic. It can be stored for several months without
5
32

Aromatic Bromination of Aldehydes and Ketones
a
Table 1. Solvent-Free Bromination of Aryl Aldehydes and Ketones Using [BBIm]Br3
Entry
Carbonyl compound
Productb
Time
Yield
(%)
0
M.p.
(°C)
-
(
min)
120
1
2
3
Benzaldehyde
No reaction
4-Methoxybenzaldehyde
3,4-Dimethoxy benzaldehyde
3-Bromo-4-
methoxybenzaldehyde
6-Bromo-3,4-
25
20
91
82
52-53
147-149
dimethoxybenzaldehyde
No reaction
5-Bromo-4-hydroxy-3-
methoxy benzaldehyde
6-Bromo-3-
4
5
1-Naphthaldehyde
Vanillin
120
2
0
98
-
165-167
6
3-Hydroxy benzaldehyde
8
95
130-132
hydroxybenzaldehyde
5-Bromo-salicylaldehyde
7
8
Salicylaldehyde
30
95
98
103-105
116-117
2,4-Dihydroxy benzaldehyde
5-Bromo-2,4-
Immediately
Immediately
dihydroxybenzaldehyde
5-Bromo-2-Hydroxy-4-
methoxybenzaldehyde
No reaction
No reaction
5-Bromo-3-
9
2-Hydroxy-4-
98
120-122
methoxybenzaldehyde
2-Nitrobenzaldehyde
4-Bromobenzaldehyde
o-Vanillin
1
1
1
0
1
2
120
120
2
0
0
96
-
-
124-125
methoxysalicylaldehyde
3-Bromoacetophenone
6-Bromo-3-
1
1
3
4
Acetophenone
3-Hydroxyacetophenone
10
10
83
91
-
75-76
hydroxyacetophenone
aAll reactions were carried out with 1.0 equiv. of [BBIm]Br
H NMR and spectral data.
at room temperature. All compounds showed satisfactory
b
3
1
Br
Bu
Br3
Bu
+Br2
N
N
N
N
Bu
Solvent-free Bu
1
2
Scheme 1. Preparation of 1,3-di-n-butylimidazolium tribromide
change of structure and loss of activity. Even after a prolonged
heating at 60 °C under vacuum (<5 mm Hg), [BBIm]Br was
recovered unaltered without any loss of bromine. [BBIm]Br
In our earlier report, we described the regioselective
bromination on activated ring such as anilines and phenols
3
3
using novel ionic liquids [BMPy]Br
3
and BBIm]Br [15,16].
3
was miscible with MeOH/EtOH, acetone, DMSO and other
strong polar organic solvents but immiscible with water, ether,
Although the ionic liquid BBIm]Br3 is the same, the
bromination on deactivated ring such as aromatic aldehyde
and ketone using this IL is novel. The nuclear bromination on
CHCl , and other weak polar organic solvents.
3
5
33

Borikar & Daniel
activated ring is easy; whereas on deactivated ring is difficult.
Br2
Hence, very few reports on deactivated ring have been
published by researchers. We hereby describe a highly
efficient, simple, and eco-friendly method for the
monobromination of aromatic aldehydes and ketones using
Br
Br3
+
+
+
HBr
N
N
N
N
Bu
Bu
Bu
Bu
2
1
O
O
[
BBIm]Br under solvent-free conditions at room temperature
3
with high yields (Scheme 2).
BBIm]Br proved to be an efficient brominating reagent
R
R
[
3
RT
Br
for the selective bromination of various aryl aldehydes and
ketones with complete selectivity and excellent yields. The
results of our experiment are summarized in Table 1. 2,4-
Dihydroxybenzaldehyde was cleanly monobrominated in the
absence of any solvent at room temperature by RTIL 2,
affording exclusively 5-bromo derivative of aldehydes (entry
R = H, CH3
Scheme 2
Table 2. Reusability of Ionic Lliquid [BBIm]Br
3
in the
Bromination of 3-Hydroxybenzaldehyde
8
). 3-Hydroxybenzaldehyde underwent monobromination in 8
min, whereas 2-hydroxybenzaldehyde was brominated in 30
min (entries 6 and 7). The aromatic aldehydes containing two
activating groups exhibited more activity (entries 3, 5, 8, 9 and
Entry
Cycle
1st run
Time
Yield
(%)a
(
min)
1
2
3
8
8
8
8
95
95
94
94
1
2); those containing only one activating group showed less
2nd run
activity (entries 2, 6 and 7); and the ones containing a
deactivating group exhibited no activity (entries 1, 4, 10 and
3rd run
1
1) due to its lower electron density of the benzene ring.
4
4th run
Similarly, a variety of substituted ketones underwent selective
monobromination (entries 13-15).
a
Isolated pure product.
All the reactions were quenched by adding water. This
caused precipitation of the products as solids or oils, which
were readily separated and washed with fresh portions of
water and then dried. The aqueous phase containing highly
water-soluble IL was easily concentrated in vacuo to recycle
CONCLUSIONS
In conclusion, a simple and practical method for the
selective bromination of aromatic aldehydes and ketones using
[
BBIm]Br, which then could be used to regenerate [BBIm]Br
3
with bromine (Scheme 2). Regeneration and reusability are
two significant features of ionic liquids [18]. The effectiveness
of ionic liquids, their recyclability and regeneration processes
were observed for the bromination of 3-hydroxybenzaldehyde
and found to be effective up to 4 cycles (Table 2).
proton-free room temperature ionic liquid [BBIm]Br has been
3
explored. The significant characteristics of the method which
are worth mentioning include high conversions, short reaction
time, mild reaction conditions, simple workup with good to
quantitative yields and re-usable ionic liquid.
We also observed the efficiency and applicability of other
reported reagents compared with ours (Table 3). As shown in
ACKNOWLEDGEMENTS
Table 3, [BBIm]Br afforded the products in higher yields and
3
in mild reaction conditions.
Financial support from the Department of Science and
Technology (DST), India, is gratefully acknowledged. We are
also grateful to Dr. Ganesh Pandey for his generous support
and encouragement.
The plausible mechanism is shown in Scheme 3.
[
BBIm]Br
3
exists in a rapid equilibrium with imidazolium
bromide and bromine in solution.
5
34

Aromatic Bromination of Aldehydes and Ketones
Br
Br3
+
+
+ Br2
N
N
O
N
N
Bu
Bu
Bu
Bu
O
O
O
.
.
H
O
O
H
H
H
+
Br
Br
Br Br
H
O
O
O
HO
H
H
HBr
+
Br
Br
H
Scheme 3. Plausible mechanism
Table 3. The Comparative Bromination of Vanillin Using the Reported Reagents vs. [BBIm]Br3
Entry
Reagent and conditions
Time (min)
Yield (%)
Ref.
1
2
3
4
HBr, DMSO, r.t.
12 h
120
2
72
86
98
96
[10]
[12]
-
Br /SiO /CAN, CCl , r.t.
2
2
4
[BBIm]Br
Pyridinium bromochromate,
CH COOH, heat
3
25
[9]
3
5
6
NBS/PEG-400, r.t.
1,2-Dipyridiniumditribromide-
ethane (DPTBE), solvent-free
30
30
87
94
[11]
[19]
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