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Sharma / Chemistry International 1(1) (2015) 60-70
60
Article type:
Research article
Article history:
Received 13 October 2014
Accepted 27 December 2014
Published 05 January 2015
January 2015 Issue
Keywords:
Halogenation
Oxidative bromination
Molecular bromine
Aqueous medium
Green chemistry
A fast, efficient, simple, eco-friendly, regioselective, controllable and economical
method for the bromination of aromatic compounds using AlBr3-Br2 system was
invetigated. The direct bromination of anilines and phenols with molecular bromine in
solution frequently results in polybromination, and when brominated in the existence
of oxidants, they also get oxidized rather than experiencing substitutions and in some
cases, require fortification of the amino (-NH2) group.
© 2015 International Scientific Organization: All rights reserved.
Capsule Summary: The phenol and aniline can be directly converted into polybrominated produced using molecular bromine,
however, in the presence of oxidant may oxidized instead of substitution.
Cite This Article As: S.K. Sharma. Eco-friendly and fast bromination of industrially-important aromatic compounds in water using
recyclable AlBr3-Br2 system. Chemistry International 1(1) (2015) 60-70.
INTRODUCTION
The selection of new bromination methods have been used
along with the conventional reagent-bromine to improve the
efficiency and selectivity (Pingali et al., 2010). Few examples are
Br2/SO2/Cl2 (Surine and Majewski, 1968, Hai and Nelson, 1991),
Br2/SbF3/HF (Bedekar et al., 2005), Br2/Ag2SO4 (De La Mare,
1976), Br2H2O2 (Encyclopedia of Chemicals, 1990),
Br2/H2O2/LDH-WO4 (Adimurthy et al., 2006), Br2-silica
(Zolfigol et al., 2007) etc. However, the use of corrosive
material (SO2Cl2, SbF3/HF, H2O2) or VOSs and discharge of
harmful hydrogen bromide as effluent waste makes these
procedures cumbersome with regards to both industrial and
environmental viewpoints. Oxybromination (such as
LiBr/CuBr2O2) (Hosseinzadeh et al., 2010) NaBr/HNO3/H2O2-
WOX supported on SBA-15 (AI-Zoubi and Hall, 2010),
Bu4NBr/AIBr3/NH4VO3/O2 (Beckmann et al., 2013),
KBr/HNO3/(CH3CO)2O (Chiappe et al., 2004) etc.), can be a
better alternative, however these reactions involve the reagents
(LiBr) ( Hosseinzadeh et al., 2010) in great extent, highly acidic
conditions (H2SO4 HNO3) expensive metal or other catalysts
(such as V, Mo, Cu, TiOx, WOX) and toxic and harmful oxidants
(H2O2, HNO3-(CH3CO)2O) (AI-Zoubi and Hall, 2010;
Beckmann et al., 2013; Chiappe et al., 2004) which enhanced the
cost of reagent and release dangerous pollutants to the
environment, consequently, none of the oxidative method has
been commercialized till now for the synthesis of commercially-
important brominated compounds due to the hazards (Benitez et
al., 2011) involved with H2O2. Other analogues of bromine,
such as tetralkylammonium tribromides (TAATB) (Borikar et al.,
2009), pentylpridinium tribromide (PPTB) (Chinnagolla et al.,
2013), ethylene bis(N-methylimidazolium) ditribromide (Ceska,
1975), [BMPy]Br3 also can be used for the bromination of many
aromatic Compounds (Chiappe et al., 2004).
On the other hand, these brominating agents are loaded with
Chemistry International 1(1) (2015) 60-70
Eco-friendly and fast bromination of industrially-important aromatic compounds in
water using recyclable AlBr3-Br2 system
Sushil Kumar Sharma
Freelance Consultant QA, India
*Corresponding author's e-mail: [email protected]
A R T I C L E I N F O A B S T R A C T
Sharma / Chemistry International 1(1) (2015) 60-70
61
several disadvantages including their low atom economy,
removal of toxic and harsh hydrogen bromide byproducts waste,
poor reprocessing of used up reagent, and the Br2 required for
their synthesis. Hence, to remove a two-stage bromination
wherein these reagents are first prepared using Br2 prior to
bromination of organic compounds, we have efficiently used
molecular bromine at the first accompanied by an eco-friendly
reagent AlBr3 for a quick and simplistic bromination of
industrially important compounds. Because of the above reasons,
molecular bromine is still a aim alternative for industrial
professionals to develop an eco-friendly haloginating agent has
numerous advantages: cost economical, low poisonousness to
humans, easy availability, fast bromination under normal
environmental conditions, rejuvenation and recyclability of
reagent up to four cycles by an inherent reprocessing of
hydrogen bromide to AlBr3, and the exceptionally simple and
clean examination of products that suggest an significant goal in
the context of ― green synthesis.
We report how an aqueous AlBr3-Br2 system without any
additional catalyst and oxidant is an effective and greener
technique for bromination of commercially important aromatics
under mild and HBr waste-free conditions. A sequence of
industrially-important substituted phenols, anilines, aldehydes,
and anilides etc, were imperiled to bromination (Scheme1).
Aromatic primary, secondary and tertiary amines were also
noticed and show a outstanding reactivity, which actually get
oxidized under ordinary bromination surroundings instead of
undergoing substitution.
OBJECTIVE
The direct bromination of anilines and phenols with molecular
bromine in solution frequently results in polybromination, and
when brominated in the existence of oxidants, they also get
oxidized rather than experiencing substitutions and, in some
cases, require fortification of the amino (-NH2) group. Though
bromination of aromatic compounds by elemental bromine is a
eminent organic reaction, bromination using elemental
bromine frequently results in a complex mixture of mono-, di-,
tri-; and even tetra-brominated products. Henceforth to date,
there has been no simple, economical, instant, easily available,
and high yield method established that can be commercialized
for the said purpose.
A diversity of new bromination techniques have been
employed along with the predictable reagent―bromine to
increase the effectiveness and choosiness. Still, the use of
poisonous and expensive reagents, catalysts, volatile organic
solvents, low yields and discharge of corroding HBr waste
circumvent these processes from industrial application.
Oxybromination can be a good substitute. Nonetheless these
reactions needs a great additional of the reagents, highly acidic
conditions, costly metal or other catalysts and harmful oxidants
which is highly expensive and release noxious waste to the
environment.
Substitute equivalent of bromine, such as organic
ammonium tribromides and various tribromide-ionic liquids
likewise are being used for the bromination of aromatic
compounds. Nonetheless, these agents are loaded with many
disadvantages including their low atom energy, disposal of
poisonous and harsh hydrogen-bromide byproducts waste, non-
effective recycling of consumed reagents, and the Br2 required
for their preparation.
Henceforward to exclude a bi-step bromination
wherein these reagents are first prepared using molecular Br2 earlier to halogenation of organic compounds, one must have
efficiently consumed Br2 at the first place with an eco- friendly
reagent AlBr3 is a prompt and facile brominating reagent for
industrial Purposes. Due to these reasons, molecular Br2 is still a
target substitute for industrial processes to progress an eco-
friendly brominating system which works under favourable
conditions. Taking these points in to consideration, we find an
aqueous AlBr3-Br2 system to be a better substitute.
EXPERIMENTAL
Investigative reagent grade starting material, reagents, solvents
and other required chemicals during study were obtained from
commercial traders and were cast-off without any further
purification. High Performance Liquid Chromatography
(HPLC) investigations were performed using a water 2695
device with PDA detector, column C18 (250 mm×4.5
mm×5µm), solvent system of 70 per cent Methanol + 30
percent water, flow rate of 1mL /minute. HPLC purity is
recorded by area per cent in graph. NMR- spectra were studied
in DMSO and CDCl3 on a Bruker Avance- II 400 NMR
spectrometer instrument; the chemical shifts were recorded in
δ ppm unit, 1H NMR (relative to TMS referenced as 0.00 ppm)
and 13
C-NMR (comparative to DMSO referenced as fourty (40)
ppm). GC/MS studies were performed using Agilent 5893(GC)
using Chemstation software; HP5-MS column, 35 meter x
0.25 mm x 0.25 micron; detector- mass; mass-range- 15 amu
to 650 amu; flow-2 ml/minute; injector temp-280 °C; volume
injected-1 microlitre of 5 per cent solution in methanol. Mass
spectral studies were carried out by Micromass Quattro Micro
API triple quadrupole MS equipped with a standard APCI-ion
X
Yaq AlBr 3 - Br 2 (n moles)
Solvent, 5-30 min, r.t.
Yield 85-99%
X
Y
Br (n)
X = OH, NH 2, NHCOMe, NHCOPh, CHO, COOH
Y = H, OH, NO 2, SO2, NH 2
Scheme 1: Bromination of substituted aromatic compounds using
aq. AlBr3-Br2 system
aReaction conditions: Substrate, 10 millimole; Substrate: Potassium
bromide:Molecular bromine = 1:1:1 (for mono-), 1:2:2 (for di-) and 1:3:3 (for tribromination); Acetic acid, 10 mL; water, 5 mL; H2SO4, 1 mL; temp,
25 °C and b Reaction conditions: Substrate, 10 millimole; Substrate:
Aluminium tribromide:Bromine = 1:1:1 (for mono-), 1:2:2 (for di-) and 1:3:3 (for tribromination); Acetonitrile, 10 mL; water, 5mL; temp, 25 °C.
Sharma / Chemistry International 1(1) (2015) 60-70
62
source. The UV spectra studies were documented on a Chemito
UV-2600 double beam UV-vis spectrophotometer in the range
of 200-400 nm wavelengths.
Distinctive method for the Bromination and synthesization of
2,6-Dibromo-4- nitroaniline (II): To a solution of AlBr3 (3.99
g) in water (5 mL) was added bromine (3.2 g, 20 mmol), and the
resultant mixture was stirred at 25°C to form a dark reddish-
brown clear solution. this solution was added quickly to a stirred
mixture of 4-nitroaniline (1.3813 g, 10 mmol) in ACN (10 mL)
taken in a 100 mL round bottom flask by using a pressure-
equalizing funnel within 2 to 3 minutes. The color disappeared
at once and thick yellowish precipitate of 2,6-dibromo-4-
niroaniline were achieved within 5 min (recorded by TCL) of
reaction time at 25°C. The reaction was appeased by adding
Fig. 1: HPLC chromatogram of 2,4,6 tribromophenol (1d)
Fig. 2: 1H-NMR and MS band of 2,4,6-tribromophenol (1d)
Fig. 3: 1H-NMR and Infrared spectra of 2,4,6-tribromophenol (1k)
Fig. 4: GC-MS of 2-bromo-4-nitroaniline (1k)
Sharma / Chemistry International 1(1) (2015) 60-70
63
water (15 mL) to separate the precipitated product. The
precipitated reaction mass was parted by vacuum filtration
utilizing a Buchner funnel, then washed twice with de-ionized
water and dried in oven at 100°C to get a yellow powdered of
2,6-dibromo-4-nitroaniline. The total isolated yield was 2.9033 g
(98.50 per cent) with an HPCL purity of 99.54 percent. The
filtrate was rescued for the next run of process. The
characteristics data documented for the isolated product were
mp 206°C (Sharma and Agarwal, 2014) (206-208°C); Infrared
IR (KBr): 3470, 3372, 3074, 2933, 2726, 2350, 1504, 1528,
1422, 1305, 1290, 1260, 1110, 943, 840, 831, 722, 655, 583,
518, 446 cm-1
, 1
H NMR (400MHz, DMSO) δ: 8.21 (s, 2H,
Ar), 6.66 (S, 2H, NH2); MS (APCI) m/z called. For
C6H4Br2N2O2: 292.8, found 289.5.
Method for Regenerating and Reprocessing of AlBr3 (Recycle 1): The aq AlBr3-Br2 solution was added promptly
within 3 to 4 min to the stirred solution of 4-nitroaniline by
using a pressure equalizing funnel. Instantaneously following
addition, the bromine color disappeared and yellowish dense
precipitates of 2,6-dibromo-4-nitroaniline were achieved within
10 min of reaction time at 25°C. The precipitated 2,6-dibromo-4-
nitroaniline was separated from the mother liquor by
vacuum filtration and then washed twice with deionized
water and dried in oven at 100°C. The 2,6-dibromo-4-
nitroaniline was obtained in 2.9006 g (98.02per cent) yield with
mp of 206°C and pureness of 99.42per cent. The
characteristics data documented for the isolated product were
found to be same as given in the above general method. The
HBr evolved was again nullified; a solvent was distilled-off, and
the aqueous layer was reused in the next run with a surplus
Fig. 5: 1H-NMR and IR spectra of 2,6-dibromo-4-nitroaniline (1l)
Fig. 6: HPLC chromatogram and MS of bromoxynil (1v)
Fig. 7: 1H and 13C-NMR spectra of bromoxynil (1v)
Sharma / Chemistry International 1(1) (2015) 60-70
64
amount of Br2.
Procedure for recycle 2,3 and 4: Alike to the above procedure
of Reprocess 1, bromine (3.2 g, 20 mmol) was added to the
aqueous layer achieved after the separation of 2,6- dibromo-4-
nitroaniline and the reaction progressed in a similar fashion with
4- nitoaniline (1.3813 g, 10 mmol) in every cycle.
The Synthesis route for 2-Bromo-4-nitroaniline (1k): The
method for the synthesis of 2,6-dibromo-4-nitroaniline was the
similar as it was given in the general procedure apart from 1
molequiv of AlBr3-Br2 were charged against 1 mol of 4-
nitroaniline(O2NC6H4NH2).
Beginning with 4-nitroaniline
(1.3813 g, 10 mmol), the
experiment gave greenish yellow
powdered of 2-bromo-4-
nitroaniline in 2.0689 g (95 per
cent yield and 98.4 per cent
HPLC purity) within 15
minutes of reaction time at
room temperature; mp 102-
104°C (Sharma and Agarwal,
2014) (104°C); Proton NMR
(400 MHz, Chloroform-d) δ
value: 4.88 (bs, 2H, NH2), 6.78
(d, 1H, J=4.48 Hz, Ar), 8.12 (dd,
1H, J=2.52 Hz, Ar), 8.42 (d, 1H,
J=2.38 Hz, Ar); IR (KBr): 3489,
3371, 1622, 1585, 1487, 1315,
1302, 1263, 1120, 895, 820,
746, 698, 638, 430, 419 cm-1
;
MS Atmospheric Pressure
Chemical Ionization (APCI)
m/z (mass-to-charge ratio)
called. For C6H5BrN2O2:217.02,
found 216.
The Synthesis path of 2,4,6-
Tribromophenol (1d): At this
point, 3 Mole equivalent of
AlBr3-Br2 was booked against 1
mole equivalent of phenol, and
the reaction pattern observed
same as reported in the general
procedure. Starting with phenol
(C6H5OH) (0.9503 g. 10 mmol),
the experiment gave white
crystals of 2,4,6-tribromophenol
immediately within 10 minutes
of reaction time at room
temperature ( 25°C) in 3.2123
g (97.10 per cent yield and
99.67 per cent HPCL purity);
mp 92°C (Sharma and Agarwal,
2014) (92-94°C); Proton NMR
(400 MHz, Chloroform-d) δ
value: 5.9 (bs, 1H, OH), 7.57
(s, 2H, Ar); IR (KBr): 3407,
3070, 2358, 1552, 1454, 1379, 1317, 1263, 1158, 856, 736,
667, 552 cm-1
; MS Atmospheric Pressure Chemical Ionization
(APCI) m/z (mass-to-charge ratio) called for C6H3Br3O:
330.79, found 330.
Investigational Route for Ultraviolet–Visible Assessments:
All Assessments were carried out at room temperature (25°C) in
the wavelength range 200-400 nm. An aq. Solution of reagent
AlBr3-Br2 was prepared by mixing a solution of 2.5 × 10-4
M
Bromine ( Br2) to a solution of 2.1 × 10-4
M Aluminium
tribromide ( AlBr3) , and the UV spectrum for the solution was
Table1: A Comparative bromination of substituted anilines and phenols between aq. KBr3 and aq
AlBr3-Br2 system
Entry Substrate Product aq KBr3a aq AlBr3-Br2
b
Time
(Min)
Yield
(%)
Time
(Min)
Yield
(%)
1.
NH2
O2N
NH2
O2N
Br
60 81 35 91
2.
NH2
O2N
NH2
O2N
Br
Br
Br
60 92 30 95
3. NH2O2N
NH2O2N
Br
60 72 12 95
4. NH2O2N
NH2O2N
Br
Br
60 89 15 97
5. OH
OH
Br
60 92 8 96
6. OH
OH
Br
Br
60 92 25 98
Sharma / Chemistry International 1(1) (2015) 60-70
65
documented by Ultraviolet-visible spectroscopy, taking the
above solution in a cuvette using a micropipette to get more
accuracy in sampling. When recorded higher than expectable
absorption resulted between the range of 200-400 nm
wavelength, the solution was thrown out and a appropriate
diluted aliquot of aqueous AlBr3-Br2 solution was taken into
the cuvette using micropipette, and a graph was documented
that gave an strong peak band of Br3-
at 266 nm wavelength. A
Part of 2 × 10-4
M solution of acetanilide (CH3CONHC6H5)
dissolved in Acetonitrile (MeCN) formerly dispensed to cuvette
which was already half-filled with aqueous solution of AlBr3-
Br2. The absorption peak at 252 nm was achieved and
documented that relates to p- bromoacetanilide. Alike procedure
was carried out to analyze the bromination of salicyclic acid
(C7H6O3) in Actonitrile (MeCN) solution.
RESULTS AND DISCUSSION
Aqueous AlBr3-Br2 reagent system is a mild, efficient, and
cost effective brominating reagent which is readily prepared
by addition of molecular Br2 to an aq. solution of Aliminium
tribromide at room temperature condition (25±10C). This
reagent was quickly added to a stirred solution of 10 millimole
of substrate liquefied in 10 mL of solvent (Table 2). By this
system, a maximum quality of halogenated products was
shaped within few minutes of time. Once the reaction was
finished, the reaction mix was appeased into H2O and solid
halogenated yields was washed-off, splashed with water, and
dried. The finish product doesn’t require extra purification. The
finish products were acknowledged by different identification
techniques and tools like: melting point, mass spectroscopy,
and NMR spectroscopy; the yields were calcuted by the
gravimetrically. The same system has been applied effectively
to a diversity of commercially-important substrates (Table 2).
Furthermore, the regioselectively of Chemical reactions is in
settlement with the known leading capability of the substituent
functional groups. The p-substitution product was the only
isomer isolated where both ο-position. Overview of an
electron-withdrawing group to the aromatic ring significantly
diminished the rate of ring bromination.
Primarily, the dibromination of 4-nitroaniline 11 as a
perfect compound using 2 equivalents of aqueous AlBr3-Br2 combination in various solvents was studied. The solvents such
as acetonitrile (ACN), methanol, acetic acid, and
dichloromethane were strained. It was observed that ACN
solvent has demonstrated to be outstanding in the process of
dibromination of 4-nitroaniline to get 2, 6-dibromo-4-
nitroaniline within 10 miniutes regarding yield (98.05per cent),
melting point (206 0
C), yellow color in crystalline powder
form, and texture of the product. Subsequent, the effect of Br2 and AlBr3 concentration on the yield and melting point of 11
were inspected in acetonitrile solvent. It is understandable from
Fig. 1 that the product quality is intensely dependent on the
mole ratio of Br2/4-NA. It was found that the optimum yield
of finished DBNA and the preferred Mp of 206 0C (Sharma
and Agarwal, 2014) (206-208 0
C) were achieved at the mole
ratio of Br2/4-NA =2/1 in the bromination process of 4-NA by
an aqueous AlBr3-Br2 system that was used as brominating
agent. The yield of the product becomes stable if further the
mole ratio decreased from Br2/4-NA from 2 to 1.2. The yield
of the products was further decresed to 93per cent with the
Mp of 198-200 0C which was not within the obligatory
standards when we declined the mole ratio of Br2/4-NA = 2 to
1.8. Similarly an under-brominated product (88 percent) was
obtained that melts within 160 - 170 0C when the mole ratio
was decreased from 1.8 to 1.65. It was observed that
monobrominated 4-nitroanilines were obtained at the mole
ratio of Br2/4-NA = 1.5 and 1.25, which melt at 102 0C and
100-101 0C, correspondingly (melting point of 2-bromo-4-
nitroaniline is 104 0C) (Sharma and Agarwal, 2014).
Brominating agent (AlBr3-Br2); the optimum yield and
desired melting points were obtained at mole ratio of AlBr3:4-
NA = 2:1. The yield of the product incr eased from 91 to 98
per cent when we upsurge the mole ratio of AlBr3/4-NA from
0.25 to 2.0, however the melting point does not change. The
function of AlBr3 catalyst was confirmed by proceeding a
reaction for 1 hr at 25 0C using a brominating agent ie.
molecular Br2 where a complex mixture of under- brominated
4-nitroaniline was achieved that melts within the range of 160
to 190 0C. Therefore, from these findings, it is concluded that
the optimum mole ratio of 4-nitroaniline to AlBr3 to Br2 was found to be 1:2:2 that is perfect for the di-
bromination of 11. It was observed that the Liquid
Chromatography-Mass Spectroscopy analysis of end product
achieved at the mole ratio of 1:2:2 shows 99 percent pure 2,6-
dibromo-4-nitroaniline, 1 percent monobrominated 4-
nitroaniline, and 0.06 per cent starting material (Table 3, entry
4).
The bromination of acetanilide (1a) and benzanilide
(1b), under these conditions, took place selectively and only p-
brominated products with no detectable o-bromo or
dibromocompounds were inaccessible in excellent yields.
Aniline 1e and phenol 1d were tribrominated to their consistent
bromo-derivations in outstanding yields (97 per cent with
1:3:3 molar ratio of substrate:AlBr3:Br2). In case if both
meta- and o.p-directing functional groups are present on the
hetrocyclic aromatic ring, only the o.p-directing group will
directs the incoming bromination ion as perceived in case of o-
nitrophenol 1e. Anilines comprising an electron-withdrawing
group can also brominate using brominating system at ambient
temperature. An aquous solution of AlBr3/Br2 can be
effectively used for the bromination of several deactivated
anilines 1g-11 proficiently and promptly upon admixing these
with it, which is somewhat tedious by other methodologies
(Das et al., 2007). It was observed that oxine (1m) and
sulphanilamide (1n) could also be successfully brominated
using 5,7-dibromo-oxine and 3,5-dibromosulphanilamide of
pharmaceutically importance, in yield of 95 and 93 per cent,
correspondingly, within 15 minutes of the reactions time.
I t w a s a l s o f o u n d t h a t s ubstrates 1p and 1q
showed good reactivity that results in a clean synthesis of 2,4-
dibromo-1-naphthol (97 per cent) and 3,5-dibromosalicylic acid
(91per cent) after 15 and 20 minutes, respectively. Similarly,
the aldehydes (1o and 1r) were also efficiently brominated in
outstanding yield (97 and 94 per cent) with the use of 2
counterparts of aquous AlBr3-Br2 solution. Bromination of β-
Sharma / Chemistry International 1(1) (2015) 60-70
66
Table 2: Bromination of various aromatic compounds using aqueous AlBr3-Br2 systema
Entry Substrate Product Time
(Min)
Yieldb
(%)
Mp
(°C (lit.))
Applications
1a NHCOPh
NHCOPhBr
18 97 (202)
200-202
Pharmaceutical intermediate
1b
OH
OH
Br
Br
Br
12 96 (92)
92-94
Reactive flame retardant
1c OH
NO 2
OH
NO2
Br
Br
25 97 114 (116-
117)
Anthelmintic or in combination with
parasiticides and antibacterials
1d
NH2
NO 2
NH2
NO 2
Br
15 90 108 (110-
113)
Fine organic and custom intermediate
1e NH2
NO 2
NH2
NO 2
Br
Br
16 95 127-129 (129-
133)
Pharmaceutical intermediate
1f NH2
O2N
NH2
O2N
Br
25 91 126-130 (128-
132)
Organic intermediate
1g NH2O2N
NH2O2N
Br
17 94 102-104 (104) Intermediate for dyestuff
1h
NH2O2N
NH2O2N
Br
Br
12 99 206 (206-
208)
A potent antifungal in the preparation
of diazonium salts used in the
synthesis of oligomeric disperse dyes
1i SO2NH2NH2
SO2NH2NH2
Br
Br
15 94 235 (235-
237)
Pharmaceutical intermediate
Sharma / Chemistry International 1(1) (2015) 60-70
67
Naphthol (1s) under identical reactions resulted in
excellent yield (97 percent) within 5 minutes, while for 1t,
two equivalents of aqueous AlBr3-Br2 and 30 minutes of
reaction time were essentially required. Similarly 5-
bromovanillin 1u, an industrially-important compound, was
also obtained from vanillin in good yield within 30 minutes.
This substrate undergoes bromination f o r a longer p e r i o d
o f time and resulted in low yields (Deshmukh et al., 1998).
The selective contact herbicide bromoxynil 1v was also
achieved in 98 per cent yield in 15 minutes of reaction time.
Table 3 shows the High Performance Liquid
Chromatography (HPLC) purity of few representatives
brominated products that determined that the high yields of
mono-, di-, and tribrominated products can be regioselectively
achieved by simply incresesing the molar equivalents of
substrate/AlBr3/Br2, in the ratio of 1/3/3 for mono-, 1/2/2 for
di- and 1/3/3 for tribromination of aromatic compounds. By
implementing an eco-friendly workup procedure, further we
have modified our green approach to bromination. The reaction
supported a simple isolation procedure composed of filtration
of solid brominated products due to absence of organic waste
and chlorinated organic solvent. This process generates an
added amount of Aluminium tribromide in the filtrate. The
solvent obtained in filtrate was distilled-off and reclaimed in
the next run of process. From the filtrate the solvent was
distilled out and can be used in the subsequent brominations. In
this way, 7 mol of AlBr3 was isolated in the end after four runs,
starting with 2 mol of Aluminium tribromide wrt 1 mol of 4-NA
in the fresh batch. By this the problem of conventional
methods associated with discharge of Hydrogen bromide
byproducts waste was successfully elliminated which otherwise
is very toxic, corrosive, and cause great pollution in the
environment. As far the mechanism of bromintion using
bromine is concerned, probable brominating classes which can
be made in aq. bromine solutions are HOBr, BrO-, Br3
-
correspondingly. The UV-vis spectral characteristics are
reported in Table 2 for numerous brominating species. The UV-
vis studies were carried out to identify the dynamic brominating
species. Equimolar solution of 1 molar equivalent aluminium
tribromide and 1 molar equivalent Br2 was prepared. The UV-
vis spectrum for this was recorded that gives a powerful
band at 266 nm wavelength. In agreement with available
studies, the band that appears at 266 nm wavelength can be
attributed due to the formation of a charge-transfer complex
between Br2 and aluminium tribromide. It is possible that
266 nm wavelength band was mainly due to tribromide ion
(Br3) that absorbs in the same region and which could arise as
depicted thruough the formation of a 1/1 AlBr3-Br2 complex.
Water that is used for the preparation of aqueous AlBr3-Br2 solution also support the formation of tribromide through the
well-defined H2O-Br2 reaction discharging bromide ion and as
found in UV- vis study. When equimolar amounts of Br2 and
AlBr3 were employed, the formation of tribromide is
considerable and no formation of pentabromide ion (Br5-) was
discovered such concentrations of Br2 as it required a higher
Table 2: Continuous….
1j CHOOH
CHOOH
Br
Br
17 98 183 (181-
185)
Pharmaceutical Intermediate
1k COOH
OH
COOH
OH
Br
Br
22 92 225 (224-
227)
Bactericide when incorporated in to
topical ointments
1l CHO
OH
CHO
OH
Br
Br
14 95 80 (80-84) Pharmaceutically acceptable salt as
inhibitor of stearoyl-CoA desaturase
useful for the treatment of obesity
1m
CHO
H3CO
OH
CHO
H3CO
OH
Br
25 96 166 (164-
166)
In pharmaceutical flavor pesticide
chemical and organic synthetic
industries
a Confirmed by comparative study of some authentic samples. All the reactions were carried out on 10 millimole scale; molar equivalents of substrate:
AlBr3:Br2 =1/1/1 (monobromination), 1/2/2 (dibromination-) and 1/3/3 (tribromination); Acetinitrile 10 mL; water 5 mL; room remperature and b Yield of final products
Sharma / Chemistry International 1(1) (2015) 60-70
68
Table 3: The selectivity of Product from starting material in the bromination of various aromatic compounds
using aqueous AlBr3-Br2 system
Entry
Substrate
Substrate
AlBr3:Br2
Product Yielda
(%)
Product Purityb (%)
Main
product
Others
1.
SO2NHNH2
1:2:2
SO2NHNH2
Br
Br
94 97.93 2.07
2.
COOH
OH
1:2:2
COOH
OH
Br
Br
90 96.80 3.20
3.
CHO
OH
1:2:2
CHO
OH
Br
Br
95 95.85 4.15
4.
NH2O2N
1:2:2
NH2O2N
Br
Br
97 99.00 1.00
5.
NH2O2N
1:1:1 NH2O2N
Br
95 98.20 1.80
6.
NH2
No2
1:2:2
NH2
No2
Br
Br
96 93.20 6.80
7.
NH2
No2
1:1:1 NH2
No2
Br
91 98.90 1.10
8.
OH
1:3:3
OHBr
Br
Br
98 99.10 0.90
a Isolated Product Yields and b Purity of end products by High Performance Liquid Chromatograph (HPLC)
Sharma / Chemistry International 1(1) (2015) 60-70
69
amount of Br2 as it required a higher amount of Br2 in
solution. This was also confirmed by UV-vis spectrum of
aqueous bromine solution (with added bromide) that does not
show any absorption of Br5-
ion (λmax = 315 nm). The
acetanilide solution wa s dissolved in Acetonitrile (ACN)
then added to aqueous AlBr3-Br2 solution and UV-vis spectrum
was documented. The prompt desertion of Br3-
peak shows that
bromine molecule (Br2) has been polarized and dissociated in
presence of added metal bromide and the produced
Brominium ion (Br+)
has been relocated to the acetanilide.
This was confirmed by the presence of a peak (λmax = 252
nm), which resembles to p-bromoacetanilide. This shows that
Br3-
is the active brominating class involved in the reaction that
generates the eletrophile Br+ and ruled out the formation of
HOBr and BrO- species as no characteristics absorption bands
of these species were witnessed before and after the reaction.
Such species are somewhat formed under the condition of
oxidative bromination defined elsewhere. Bellucci et al. have
suggested a mechanism for the addition of Br2 to olefins using
tetrabutylammonium tribromide as a brominating agent. This
mechanism clarifies the catalytic effect of added bromide salts
by the fact that they are involved in the rate-datermining step.
Considering the UV-vis results of the present study and
also considering the result pattern of Bellucci et al., it can be
projected that the binding of AlBr3 to Br2 molecule involves
the breakage of a Br-Br bond to give a bromonium-
tribromide (Br3-) intermediate ion pair. In this reaction, the
added AlBr3 acts as a catalyst that instantaneously polarized the
Br2 molecule and produces bromonium ion (Br3-). A transition
state reflects brominium ion mechanism which shows the
nucleophilic attack at the bromine by the electron-rich Π-
system of activated ring was suggested. This reports a
relocation of Brominium ion (Br+)
to the substrate from a
tribromide ion-pair intermediate Al[Br+Br
-(Br
δ+---Br
δ-)] and
ring-bromination occurs by brominium ion, Br+-relocation
mechanism. The ―salting out effect of ions over bromine (Br2),
effects in the establishment of ion-dipole complex increases the
activity-factor of Br2 in solutions of metal halides. At the end,
transition state breakup to give brominated end product and
hydrogen bromide (HBr) as reaction byproduct.
CONCLUSIONS
A new, cost effective, efficient, and simple bromination
protocol is determined and disclosed for mono-, di-, and
tribromination. The features of this –green process includes the
use of cost efficient aqueous AlBr3-Br2 solution as a effective
brominating agent which can be invigorated simply even at
commercial level applications. This method is free from strong
acids, organic solvent and HBr- byproducts waste during the
reactions, which are very common in old and existing protocol,
which makes this protocol eco-friendly because of zero effluent
discharge to the environment, consequently, a good choice to
existing bromination methods.
The categorization data (1H NMR, Infrared and Mass
Spectroscopy) achieved for various representative compounds
are given below:
2,6-Dibromo-4-nitophenol (1f): Off white powder; 1H-NMR
(410 MHz, Chloroform CDCl3) δ value: 7.335 (s, 1H).
7.21 (s, 1H), 5.54 (bs, 1H) 2.27 (s, 3H); I n f r a r e d ( IR)
(KBr): 3385, 3369, 3084, 1572, 1514, 1462, 1408, 1323, 1232,
1217, 1147, 1128, 899, 742, 694, 592, 517 cm-1
. 4-Bromo-2-
nitroaniline (1g): Orange crystalline powder; IR (KBr):
3474, 3354, 1639, 1631, 1622, 1591, 1556, 1505, 1454, 1402,
1365, 1338, 1250, 1165, 1118, 1107, 1076, 1032, 885, 876,
816, 764, 706, 631, 519, 443, 426, 416 cm-1
; MS, Atmospheric
Pressure Chemical Ionization (APCI) m/z (mass-to-charge
ratio) called. for C6H5BrN2O2:217.02, found 216. 2,4-
Dibromo-6-nitroaniline (1h): Orange-yellowish powder; 1H NMR (400 MHz, Chloroform ‘CDCl3) δ value: 8.28 (S,
1H), 7.81 (s, 1H), 6.64 (bs, 2H); IR (KBr): 3468, 3354, 3088,
1626, 1564, 1545, 1496, 1446, 1387, 1346, 1319, 1259, 1227,
1120, 1099, 889, 875, 761, 692, 542, 455, 414 cm-1
MS, Atmospheric Pressure Chemical Ionization (APCI) m/z
(mass-to-charge ratio) called for C6H4Br2N2O2:295.92,
found 296. 3,5-Dibromo-4-hydroxybenzaldehyde (1o):
Light brownish powder; 1H NMR (400 MHz, DMSO): δ
value: 7.99 (2H, s, ArH), 9.8 (1H, s, CHO); IR (KBr):
3191, 2863, 1774, 1676, 1637, 1582, 1549, 1482, 1418, 1381,
1366, 1330, 1305, 1242, 1204, 115, 1010, 934, 897, 810,
743, 651, 563, 546 cm-1
MS, Atmospheric Pressure
Chemical Ionization m/z (mass-to-charge ratio) called. For
C7H4Br2O2: 279.9, found 279. Bromoxynil (1v): White
crystaline; 1H NMR (400 MHz, DMSO) δ value: 10.9 (s,
1H OH), 7.90 (s, 2H, ArH); 13
C NMR (100 MHz, DMSO):
104.36, 11.28, 135.25, 155.21; IR (KBr): 3460, 2250, 620 cm-
1 MS, Atmospheric Pressure Chemical Ionization (APCI) m/z
(mass-to-charge ratio) called. for C7H3Br2NO: 276.92, found
277.
ACKNOWLEDGEMENT
Prof. (Dr.) D.D Agarwal, Sanjeev Sharma, Yatendra Sharma,
Saurabh Kumar, Dr. Ekta Sharma, Arnavi Sharma.
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