Mild, efficient, and regioselective monobromination of arylamines and phenols using [BBIm]Br3 as a new reagent

Article abstract of DOI:10.1080/00397910903009430

We report here an efficient method for the synthesis and characterization of the room-temperature ionic liquid 1,3-di-n-butylimidazolium tribromide ([BBIm]Br3) (2) and its application as an efficient reagent and solvent for regioselective bromination of arylamines and phenols under mild conditions. The bromination was carried out in the absence of organic solvents, and in most cases, the only extraction solvent needed was water. The spent 1,3-di-n-butylimidazolium bromide (1) was easily recycled.

Full text of DOI:10.1080/00397910903009430

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Mild, Efficient, and Regioselective
Monobromination of Arylamines and
Phenols Using [BBIm]Br3 as a New
Reagent
Sanjay P. Borikar a , Thomas Daniel a & Vincent Paul a
a Division of Organic Chemistry , National Chemical Laboratory ,
Pune, India
Published online: 04 Feb 2010.
To cite this article: Sanjay P. Borikar , Thomas Daniel & Vincent Paul (2010) Mild, Efficient, and
Regioselective Monobromination of Arylamines and Phenols Using [BBIm]Br3 as a New Reagent,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 40:5, 647-653, DOI: 10.1080/00397910903009430
To link to this article: http://dx.doi.org/10.1080/00397910903009430
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Synthetic Communications1, 40: 647–653, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903009430
MILD, EFFICIENT, AND REGIOSELECTIVE
MONOBROMINATION OF ARYLAMINES AND
PHENOLS USING [BBIm]Br3 AS A NEW REAGENT
Sanjay P. Borikar, Thomas Daniel, and Vincent Paul
Division of Organic Chemistry, National Chemical Laboratory, Pune, India
We report here an efficient method for the synthesis and characterization of the room-
temperature ionic liquid 1,3-di-n-butylimidazolium tribromide ([BBIm]Br3) (2) and its
application as an efficient reagent and solvent for regioselective bromination of arylamines
and phenols under mild conditions. The bromination was carried out in the absence of
organic solvents, and in most cases, the only extraction solvent needed was water. The spent
1,3-di-n-butylimidazolium bromide (1) was easily recycled.
Keywords: [BBIm]Br3; ionic liquid; monobromination; regioselective; solvent-free
INTRODUCTION
Haloarylamines and halophenols are important versatile synthetic intermediates
that can be used as products.[1,2] A variety of methods using molecular bromine,[3]
transition-metal catalysts,[4] and alkali metal halides[5] have been reported in the litera-
ture. However, bromine is a hazardous chemical that is difficult to manipulate because
of its toxicity and high vapor pressure. Many brominating reagents, such as
N-bromosuccinimide (NBS),[6] tetrabutylammonium tribromide,[7] 1,8-diazabicy-
clo[5.4.0]undec-7-ene hydrobromide perbromide (DBUH) ꢀ Br3,[8] cetyltrimethylam-
monium tribromide,[9] pyridinium tribromide,[10] LiBr=ceric ammononium nitrate,[11]
and HBr=dimethylsulfoxide (DMSO),[12] are available. Bromination in classical
room-temperature ionic liquid (RTIL) media, such as [BMIm]PF6, which replace
environmentally problematic chlorinated solvents, have been demonstrated.[13] There
are some disadvantages in these methods, such as harsh reaction conditions, relatively
poor selectivity and yields, or the need for large amount of reagents, oxidants, and
catalysts. Therefore, the development of an efficient, selective monobromination
reaction of arylamines and phenols is still a major challenge in organic synthesis.
Ionic liquids (ILs) were introduced as alternative green reaction media because
of their unique chemical and physical properties of nonvolatility, nonflammability,
thermal stability, and ease of recyclability. In recent years, there has been consider-
able interest in developing green chemistry[14] for organic synthesis because of
Received February 5, 2009.
Address correspondence to Vincent Paul, Division of Organic Chemistry, National Chemical
Laboratory, Pune 411 008, India. E-mail: vp.swamy@ncl.res.in
647

648
S. P. BORIKAR, T. DANIEL, AND V. PAUL
Scheme 1. Synthesis of 1,3-di-n-butylimidazolium tribromide.
environmental demand and sustainability. Today, ILs have marched far beyond this
border, showing their significant roles in controlling the reactions as new reagents.[15]
For example, tribromide ILs based on imidazolium or pyridinium, as nonvolatile
and regioselective bromination reagents, have been developed by different groups.[16]
There are some disadvantages such as temperature conditions, poor conversion,
poor selectivity, and need for more reagent. In continuation of our ongoing program
to develop environmentally benign and new synthetic methods using ionic liquids
as novel promoters and selective reagents,[17] we report here a new and efficient
method for the regioselective monobromination of arylamines and phenols using
1,3-di-n-butylimidazolium tribromide ([BBIm]Br3).
RESULTS AND DISCUSSION
We hereby disclose the synthesis, full characterization, and reactivity of
[BBIm]Br3, a proton-free RTIL bromine analog. This does not have any measurable
vapor pressure and has been demonstrated for regioselective nuclear monobromina-
tion reactions.
This tribromide is a stable liquid, readily prepared by the addition of molecular
bromine to [BBIm]Br dropwise under stirring, that forms exothermally the red liquid
[BBIm]Br3 (density 1.55 g cmꢁ3 and viscosity 59.5 cP) (Scheme 1). Excess bromine
absorbed by 2 was removed completely under a high vacuum. RTIL 2 is hydro-
phobic, forming two phases with water, whereas the IL 1 is highly hydrophilic
and hygroscopic. IL 2 can be stored for several months without change of structure
and loss of activity. Even after prolonged heating at 60ꢂC under vacuum (<5 mm
Hg), IL 2 was recovered unaltered without loss of bromine. IL 2 was miscible with
Scheme 2. Regioselective monobromination of arylamines and phenols with [BBIm]Br3 under solvent-free
conditions.

MONOBROMINATION OF ARYLAMINES
649
Table 1. Solvent-free bromination using [BBIm]Br3 at room temperaturea
Entry
1
Substrate
Product
Time
Yield (%)b
5 min
98
2
3
15 min
95
97
Immediately
4
5
8 min
92
98
Immediately
6
2 min
97
7
8
35 min
89
Immediately
94
(Continued )

650
S. P. BORIKAR, T. DANIEL, AND V. PAUL
Table 1. Continued
Entry
9
Substrate
Product
Time
Yield (%)b
97
Immediately
10
11
3 min
8 min
98
95
12
13
13 min
15 min
97
91
14
15
8 min
95
98
Immediately
aAll reactions were carried out with 1.0 equivalent of [BBIm]Br3 at room temperature.
bAll compounds showed satisfactory 1H NMR and spectral data.
MeOH=EtOH, acetone, DMSO, and other strong polar organic solvents and
immiscible with water, ether, CHCl3, and other weakly polar organic solvents.
1,3-Di-n-butylimidazolium tribromide ([BBIm]Br3) is an efficient and novel
reagent for the regioselective monobromination of various arylamines and phenols
with complete selectivity and excellent yields (Scheme 2), and the results are summar-
ized in Table 1.

MONOBROMINATION OF ARYLAMINES
651
Phenol was cleanly monobrominated in the absence of any solvent at room
temperature by [BBIm]Br3, affording exclusively p-bromophenol (Table 1, entry
11). m-Nitrophenol was monobrominated in 8 min (entry 11). b-Naphthol, a bulky
molecule, took only 3 min for monobromination (entry 10). Similarly, a variety of
substituted arylamines and phenols underwent regioselective monobromination
(Table 1, entries 1–15).
All the reactions were quenched by adding water. This caused precipitation of
the products as solids or oils, which were readily separated, washed with fresh por-
tions of water, and then dried (either with sodium sulfate or in vacuo). The aqueous
phase containing highly water-soluble IL 1 was easily concentrated in vacuo to
recycle 1, which then could be used to regenerate RTIL 2 with bromine (Scheme 2).
All the reactions were carried out in air at room temperature, adding 1.0 equiv
of [BBIm]Br3 to an equimolar amount of substrate without any solvent. Although
the reactions were slightly exothermic, no special precautions were taken for cooling.
They were monitored by thin-layer chromatography (TLC) and stopped after the
disappearance of the substrate.
CONCLUSION
In conclusion, a new RTIL bromine analog, which is safer and easier to use,
was synthesized and characterized. It displayed improved selectivity and better reac-
tion conditions than current monobromination techniques. This new functional
[BBIm]Br3 may be classified as ‘‘green’’ for the following reasons: (1) it eliminates
toxic bromine vapors, (2) the bromine carrier [BBIm]Br can be easily recovered
and recycled, and (3) it avoids the use of organic solvents. Furthermore, [BBIm]Br3
afforded good to excellent yields for a wide variety of arylamines and phenols at
room temperature.
EXPERIMENTAL
General
1
The NMR spectra were recorded on a Bruker system (200 MHz for H and
75 MHz for 13C) using tetramethylsilane (TMS) as an internal standard. The reac-
tions were monitored by TLC using 0.25-mm Merck silica-gel plates (60F-254),
and the products were purified by column chromatography on silica gel (60–120
mesh) obtained from M=s Spectrochem India Ltd. Infrared (IR) spectra were
recorded on Perkin-Elmer Fourier transform (FT)–IR 16 PC spectrometer.
Preparation of [BBIm]Br3 Ionic Liquid
In a fume cupboard, molecular bromine (1.956 mL, 0.038 mol) was added
dropwise over 15 min to [BBIm]Br (10.0 g, 0.038 mol) with stirring and cooling in
a ice bath, affording the deep red liquid IL 2, and stirring was continued for 2 h.
Under reduced pressure over 5 h at 60ꢂC, the pure IL 2 was obtained 15.5 g
(96.1%) as a red oil. 1H NMR (CDCl3, 200 MHz): d 0.98 (t, 6H, J ¼ 7.31 Hz),
1.36 (m, 4H), 1.90 (m, 4H), 4.31 (t, 4H, J ¼ 7.52 Hz), 7.44 (d, 2H, J ¼ 8.11 Hz),

652
S. P. BORIKAR, T. DANIEL, AND V. PAUL
8.99 (s, 1H); 13C NMR (CDCl3, 75 MHz): d 12.86, 18.82, 31.60, 49.11, 121.92,
135.99; MS (ESI): 181 (M-X3). Anal. calcd. for C11H21Br3N2: C, 31.38; H, 5.03;
N, 6.65. Found: C, 31.31; H, 4.93; N, 6.50.
Typical Experimental Procedure for Monobromination of
Arylamines and Phenols
1,3-Di-n-butylimidazolium tribromide (3.3 mmol) was added to a stirred mix-
ture of arylamines or phenols (3.3 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,
and the organic layer was separated, dried over sodium sulfate, and concentrated
to afford pure monobromo arylamines or monobromo phenols.
ACKNOWLEDGMENTS
This work was carried out under Indo-Mexican Inter-Governmental joint
project (GAP 264126) and is greatly acknowledged. We are grateful to Dr. Ganesh
Pandey for his support and encouragement.
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