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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


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.


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)


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)


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


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-


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)


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)



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


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)


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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Species λmax

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Br3- 266

Br5- 315

HOBr 284, 350

BrO 329

Acetanilide 240

p-Bromoacetanilide 252


70

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