Rapid and total bromination of aromatic compounds using TsNBr2 without any catalyst

Article abstract of DOI:10.1080/00397911.2014.956367

N,N-Dibromo-p-toluenesulfonamide (TsNBr₂) has been found to be a new reagent for bromination of aromatic compounds. The reaction is extremely fast and goes into completion instantaneously at ambient temperature to produce exclusively the corresponding polybrominated product. This procedure is applicable to various phenols, anisole, and anilines to give corresponding polybrominated compound as a single product in excellent yield.

Full text of DOI:10.1080/00397911.2014.956367

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Rapid and Total Bromination of Aromatic Compounds
Using TsNBr2 Without Any Catalyst
Indranirekha Saikiaa, Pranita Chakrabortya, Manas Jyoti Sarmaa, Mridusmita Goswamia &
Prodeep Phukana
a Department of Chemistry, Gauhati University, Guwahati, Assam, India
Accepted author version posted online: 25 Sep 2014.
To cite this article: Indranirekha Saikia, Pranita Chakraborty, Manas Jyoti Sarma, Mridusmita Goswami & Prodeep Phukan
(2014): Rapid and Total Bromination of Aromatic Compounds Using TsNBr2 Without Any Catalyst, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, DOI: 10.1080/00397911.2014.956367
To link to this article: http://dx.doi.org/10.1080/00397911.2014.956367
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RAPID AND TOTAL BROMINATION OF AROMATIC COMPOUNDS USING
TsNBr2 WITHOUT ANY CATALYST
Indranirekha Saikia1, Pranita Chakraborty1, Manas Jyoti Sarma1, Mridusmita Goswami1,
Prodeep Phukan1
1Department of Chemistry, Gauhati University, Guwahati, Assam, India
Department of Chemistry, Gauhati University, Guwahati -781014, Assam, India
E-mail: pphukan@yahoo.com.
Abstract
N,N-dibromo-p-toluenesulfonamide (TsNBr2) has been found to be a new reagent for
bromination of aromatic compounds. The reaction is extremely fast which goes into
completion instantaneously at ambient temperature to produce exclusively the
corresponding polybrominated product. This procedure is applicable to various phenols,
anisole and anilines to give corresponding polybrominated compound as single product in
excellent yield.
KEYWORDS: Bromination; TsNBr2; Phenol; Aniline; Anisole; Tribromophenol.
INTRODUCTION
In recent years, bromoaromatics are finding extensive applications in organic synthesis as
versatile precursors for construction of carbon-carbon bond via transition metal mediated
1

coupling reactions [1]. They are also used as important synthetic intermediates for the
manufacture of pharmaceuticals, agrochemicals and specialty chemicals [2]
.
Polybrominated phenols such as tribrmophenol (TBP) is used as an intermediate in the
preparation of flame retardants such as brominated epoxy resins [2]. Moreover, many
bromo compounds exhibit antitumor, antibacterial, antifungal, antineoplastic, antiviral,
antioxidizing property [3]. Sodium salt of tribromophenol (TBPNa) is used as fungicide
and wood preservative [3]. In nature, TBP has been found in ocean sediments as a
metabolite of marine fauna [4]. Although bromination with elemental bromine is a well
known reaction [5], due to the hazardous effect of bromine several brominating agent were
utilized which includes examples such as NBS [6], tetraalkylammonium tribromides [7],
DBUH.Br3 [8], cetyltrimethylammonium tribromide [9], pyridinium tribromide [10]
LiBr/ceric ammonium nitrate [11], HBr [12], dioxanedibromide [13], pyridium hydrobromide
perbromide [14], DBU hydrobromide perbromide [15], tetrabromocyclohexadienone [16]
,
,
tetraalkylammonium bromides [17], hexamethylenetetramine tribromide [18], 1-butyl-3-
methylpyridinium tribromide [19], ZrBr4/diazene mixture [20], metal bromides/oxidants [21]
AlBr3 in presence of NH4VO3 [22], bromochromates [23] etc. However, in many cases, the
products contain a mixture of ortho & para products or a mixture of mono & poly
brominated compounds Moreover, it is difficult to achieve exclusive formation of
,
polybrominated products. Even use of an excess reagent results in a mixture of mono and
polybrominated compounds. Very recently, Liu et. al. reported a method for mono and di
[24]
bromination of arenes using a combination of I2O5 and KBr .
2

A most popular brominating agent NBS brominates in the aromatic nucleus when no
radical initiator is present [6a,b]. Generally, acidic catalysts such as H2SO4 [6c-e], TsOH [6f]
silica gel [6g], HZSM-5 [6h], are used with NBS for the bromination of activated aromatic
,
substrate. Other activators such as microwave or ultrasound [6i], UV radiation [6j] or ionic
liquid [6k] have also been reported for NBS assisted bromination of activated aromatics.
Bromination with NBS favoured by polar solvents like propylene carbonate [6l], DMF [6m,
n], CH3CN [6o] etc. However, in case of bromination of phenol in CH3CN, NBS gives
mixture of substrate, monobrominated phenol and corresponding dibrominated phenol
with longer time period [6p]
.
RESULT AND DISCUSSION
We have recently reported few efficient protocols for various transformations
using N,N-dibromo-p-toluenesulfonamide (TsNBr2) [25]. As a continuation of our work on
TsNBr2, we report herein a rapid procedure for bromination of phenols and anilines
(Scheme 1).
Initial experiments to study the feasibility of the reagent for bromination reaction
were carried out by taking phenol as a model substrate. The reaction was carried out by
adding TsNBr2 to the organic solution of phenol (1mmol) in acetonitrile (2mL) at room
temperature. The reaction was found to complete instantaneously to produce
corresponding bromo products. After 10 minutes exposure, the reaction mixture was
treated with sodium thiosulfate and subjected to usual work-up procedure. When 0.5
mmol of TsNBr2 was added the reaction produced a mixture of 4-bromophenol (40%)
3

and 2,4,6-tribrophenol (10%) along with unreacted phenol (Table 1). When 1 mmol of
phenol was used, the reaction produced a mixture of 4-bromo and tribromophenol. No
unreacted phenol was found. Further increment of the amount of TsNBr2 to 1.5 mmol led
to the formation of 2,4,6-tribromo phenol exclusively with 87 % isolated yield (Table 1).
The reaction was also carried out at low temperature (0 oC). In both cases 2,4,6-tribromo
phenol was obtained with similar yield in an instantaneous reaction.
After obtaining an acceptable reaction condition from the initial experiments, we
extended the procedure to varieties of substituted phenols (Table 2). However, total
bromination of substituted phenols could be achieved using 1 mmol of TsNBr2 per mole
of the substrate. It can be seen from Table 2 that different kinds of phenolic substrates
undergo total bromination reaction instantaneously at room temperature. 2-Naphthol
produced the corresponding 1,3-dibromo product in 76% yield. However, in case of 2-
aminophenol, the yield of corresponding brominated product is relatively low (Table 2,
entry 9). When, the reaction was extended to anisol, 77% of corresponding
tribrmoanisole has been obtained.
The success of the method with phenols encouraged us to extend the reaction to anilines
(Table 3). Initial reaction with aniline was encouraging. The reaction was completed
instantaneously with 90% yield of the desired tribromo aniline in presence of 1.5
equivalent of TsNBr2. In this case, however, the addition of TsNBr2 should be done at 0
°C for better yield. It is necessary to add the brominating agent at low temperature to
4

subsidize the exothermicity. Then the process was extended to variety of anilines and the
results are summarized in Table 3.
It can be seen from Table 3 that different kind of anilines could be converted to
corresponding polybrominated product in excellent yield.
EXPERIMENTAL
To a solution of the aromatic compound (1 mmol) in acetonitrile (2 ml) TsNBr2 (1
mmol) was added at 0 °C. After 10 min of stirring at room temperature, sodium
thiosulphate (200mg approx.) was added and stirred for 10 minutes. The reaction was
taken up in ethyl acetate, dried over NaSO4 and concentrated. Crude product was purified
by flash chromatography or silica gel (230-400 mesh) with a mixture of petroleum ether
and ethyl acetate as eluent.
2, 6-Dibromo-4-chloro-5-methylphenol: IR (KBr, cm-1) ν: 3430, 1595, 1442, 1380,
1308, 1219, 1171, 1028, 969, 854, 771, 707, 646; 1HNMR (CDCl3, 400 MHz) δ: 7.32 (s,
1H), 5.73 (s, 1H), 2.3 (s, 3H); 13CNMR (CDCl3, 100 MHz) δ: 148.4, 136.2, 131.2, 126.1,
113.4, 106.4, 21.0; GCMS (M/Z %) : 302 (M++2, 75), 300 (M+, 98), 265 (58), 221 (63),
139 (21), 111 (100), 75 (83), 38 (24). Elemental Analysis: C 27.56%, H 1.89%, O 6.29%
CONCLUSION
5

In conclusion, we have developed an efficient method for bromination of phenol and
anilines. The reaction completes instantaneously to produce corresponding
polybrominated product in excellent yield.
SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher’s website.
ACKNOWLEDGMENTS
Financial support from DST (Grant No. SR/S1/RFPC-07/2006 and SR/S1/OC-43/2011)
is gratefully acknowledged. IS and PC thanks CSIR for Senior Research Fellowship.
REFERENCES
[1]
Diederich, F.; Stang, P. J. Metal-catalyzed cross-coupling reactions; Wiley-VCH:
Weinheim, Germany 1998.
[2]
(a) Cannon, K. C.; Krow, G. R. Handbook of Grignard reagents; Dekker: New
York 1996; (b) Taylor R, (Ed.); Electrophilic aromatic substitution; John Wiley & Sons:
Chichester 1990 (c) Ulmann’s Encyclopedia of Industrial Chemistry, 6th ed.; Wiley:
Weinheim 1998, (d) Milne, G. W. A. (Ed.), Gardner's Commercially Important
Chemicals: Synonyms, Trade Names, and Properties., John Wiley & Sons, Hoboken,
USA; (e) Merck Index, 11th Edition, p. 9526.
[3]
(a) Butler, A.; Walker, J. V. Chem. Rev. 1993, 93, 1937; (b) Gribble, G. W. Acc.
Chem. Res. 1998, 31, 141; (c) Gribble, G. W. Chem. Soc. Rev. 1999 28, 335.
6

[4]
(a) Fielman, K. T.; Woodin, S. A.; Lincoln, D. E. Env. Toxicol. Chem.
2001, 20 738; (b) Fu, X.; Schmitz, F. J.; Govindan, M.; Abbas, S. A.; Hanson, K.
M.; Horton, R. A.; Crews, P.; Laney, M.; Schatzman, R. C. J Nat Prod. 1995, 58, 1384.
[5]
(a) Fuson, R. C. Reaction of organic compounds, Wiley, Newyork, 1962, 58; (b)
Norman, R. O. C.; Taylor, R. Electrophilic substitution in Benzenoid compounds,
Elseiver, New York, 1965, 130-132; (c) Schimid, H. Helv. Chim. Acta., 1946, 29, 1144
(d) Jacqesy, J.; Jouannetaud, M.; Makani, S.; J. Chem. Soc., Chem. Commun., 1980, 110;
(e) Gnaim, J. M.; Sheldon, R. A. Tetrahedron Lett., 2005, 46, 4465; (f) Doyle, M. P.; Van
Lente, M. A.; Mowat, R.; Fobare, W. F. J. Org. Chem., 1980, 45, 2570.
[6]
(a) Djerassi, C. Chem. Rev., 1948, 48, 271 (b) Goldberg, Y.; Bensimon, C.; Alper,
H. J. Org. Chem., 1992, 52, 6374; (c) Lambert, F. L.; Ellis, W. D.; Parry, R. J.; J. Org.
Chem., 1965, 30, 304; (d) Coleman, R. S.; Grant, E. B. J. Org. Chem., 1991, 56, 1357; (e)
Diwu, Z. J.; Lown, J. W. Tetrahedron, 1992, 48, 45; (f) Bovonsombat, P.; McNelis, E.
Synthesis, 1993, 237; (g) Konishi, H.; Aritomi, K.; Okano, T.; Kiji, J.; Bull. Chem. Soc.
Jpn., 1989, 62, 591; (h) Paul, V.; Sudalai, A.; Daniel, T.; Srinivasan, K. V. Tetrahedron
Lett. 1994, 7055; (i) Heropoulos, G. A.; Cravotto, G.; Screttas, C. G.; Steele, B. R.
Tetrahedron Lett., 2007, 48, 3247; (j) Chhattise, P. K.; Ramaswamy, A. V.; Waghmode,
S. B. Tetrahedron Lett., 2008, 49, 189; (k) Pingali, S. R. K.; Madhav, M.; Jursic, B. S.
Tetrahedron Lett., 2010, 51, 1383; (l) Ross, S. D.; Finkelstein, M.; Petersen, R. C. J. Am.
Chem. Soc., 1958, 80, 4327; (m) Mictchell, R. M.; Lai, Y –H.; Williams, R. V.; J. Org.
Chem., 1979, 44, 4733; (n) Weller, D. D.; Stirchak, E. P.; J. Org. Chem., 1983, 4873; (o)
Carreno, M. C.; Garia, Ruano, J. L.; Sanz, G.; Toledo, M. A.; Urbano, A.; J. Org. Chem.,
1995, 60, 5328; (p) Oberhauser, T. J. Org. Chem., 1997, 62, 4504; (q) Singh, P. P.;
7

Thatikonda, T.; Kumar, K. A. A.; Sawant, S. D.; Singh, B.; Sharma, A. K.; Sharma, P.
R.; Singh, D.; Vishwakarma, R. A. J. Org. Chem., 2012, 77, 5823.
[7]
(a) Buckles, R. E.; Popov, I. A.; Zelezny, W. F.; Smith, R. J. J. Am. Chem. Soc.
1951, 73, 4525; (b) Kajigoeshi, S.; Kakinami, T.; Okamoto, T.; Nakamura, H.; Fujikawa,
M. Bull. Chem. Soc. Jpn. 1987, 60, 4187; (c) Berthelot, J.; Guette, C.; Desbene, P-L.;
Basselier, J-J. Can. J. Chem. 1989, 67, 2061.
[8]
Muathen, H. A. J. Org. Chem. 1992, 57, 2740.
[9]
Cerichelli, G.; Luchetti, L.; Mancini, G. Tetrahedron. Lett. 1989, 30, 6209.
Reeves, W. P.; King, R. M. Synth. Commun. 1993, 23, 855.
Roy, S. C.; Guin, C.; Rana, K. K.; Maiti, G. Tetrahedron Lett. 2001, 2001, 6941.
[10]
[11]
[12] (a) Srivastava, S. K.; Chauhan, P. M. S.; Bhaduri, A. P. Chem. Commun. 1996,
2679; (b) Nishina, Y.; Takami, K. Green Chem. 2012, 14, 2380; (c) Khosravi, K.;
Kazemi, S. Chinese Chem. Lett. 2012, 23, 387.
[13] Yanovskaya, L. A.; Terentyev, A. P.; Belenky, L. I. J. Gen. Chem. USSR ( Engl.
Transl.), 1952, 1635.
[14]
[15] Muathen, H. A. J. Org. Chem. 1992, 57, 2740.
[16] Cram, D. J.; Dicker, I. B.; Lauer, M.; Knobler, C. B.; Trueblood, K. N. J. Am.
Rosenmund, K. W.; Kuhnhenn, W. Ber. Dtsch. Chem. Ges. 1923, 1262.
Chem. Soc. 1984, 106, 7150.
[17] (a) Bhalerao, D. S.; Mahajan, U. S.; Akamanchi, K. G. Synth. Commun. 2008, 38,
2814; (b) Kumar, M. A.; Rohitha, C. N.; Kulkarni, S. J.; Narender, N. Synthesis, 2010,
1629.
[18] Bisarya, S. C.; Rao, R. Synth. Commun. 1993, 23, 779.
8

[19] Borikar, S. P.; Daniel, T.; Paul, V. Tetrahedron Lett. 2009, 50, 1007.
[20] Stropnik, T.; Bombek, S.; Kočevar, M.; Polanc, S. Tetrahedron Lett. 2008, 49,
1729.
[21] (a) Adibi, H.; Hajipourb, A. R.; Hashemid, M. Tetrahedron Lett. 2007, 48, 1255;
(b) Wischang, D.; Hartung, J. Tetrahedron, 2012, 68, 9456; (c) Roche, D.; Prasad, K.;
Repic, O.; Blacklock, T. J. Tetrahedron Lett. 2000, 41, 2083.
[22] Kikushima, K.; Moriuchi, T.; Hirao, T. Tetrahedron Lett. 2010, 51, 340.
[23] (a) Albadi, J. Tajik, H. Keshavarz, M.; Abedini, M. Monatsh. Chem. 2013, 144,
179; (b) Mahmoodi, N. O.; Yazdanbakhsh, M. R.; Hassanzadeh, F. Oriental J. Chem.
2011, 27, 429.
[24]
J. Hou, Z. Li, Xiao-Dong Jia, Zhong-Quan Liu, Synthetic Communications.
2014, 44, 181.
[25] (a) Phukan, P.; Chakraborty, P.; Kataki, D. J. Org. Chem. 2006, 71, 7533. (b)
Saikia, I.; Phukan, P. Tetrahderon Lett. 2009, 50, 5083. (c) Saikia, I.; Chakraborty, P.;
Phukan, P. ARKIVOC, 2009, xiii, 281. (d) Saikia, I.; Kashyap, B.; Phukan, P. Synth.
Commun. 2010, 40, 2647; (e) Saikia, I.; Kashyap, B.; Phukan, P. Chem. Commun. 2011,
47, 2967; (f) Saikia, I.; Rajbongshi, K. K.; Phukan, P. Tetrahedron Lett. 2012, 53, 768;
(g) Borah, A. J.; Phukan, P. Tetrahedron Lett. 2012, 53, 3035; (h) Borah, A. J.; Phukan,
P. Chem. Commun. 2012, 48, 5491; (i) Rajbongshi, K. K.; Phukan, P. Tetrahedron Lett.
2014 55 1877; (j) Rajbongshi, K. K.; Sarma, M. J.; Phukan, P. Tetrahedron Lett. 2014 55
(http://dx.doi.org/10.1016/j.tetlet.2014.07.124).
9

a
Table 1 Bromination of phenol using TsNBr2
Entry
Phenol
(mmol)
1
TsNBr2
(mmol)
0.5
Products
Yieldb
1
4-bromophenol +
2,4,6-
40
10
tribromophenol
4-bromo phenol +
2,4,6-
2
3
1
1
1
30
50
tribromophenol
2, 4,6
1.5
87
tribromophenol
aReaction condition: acetonitrile, 2mL, rt;
bisolated yield.
10

Table 2 Bromination of phenols using TsNBr2
Entry Substrate(a) TsNBr2(equiv) Product(b) Yielda(%)
OH
OH
1
2
3
4
5
1.5
1
87
85
78
84
82
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
OH
OH
Br
Br
OH
OH
1
F
F
OH
OH
1.5
1
OH
OH
Br
OH
OH
Br
NO2
NO2
Br
OH
6
7
1
1
76
87
OH
Br
OH
OH
OH
Br
OMe
OMe
Br
OH
8
9
1
1
95
69
Br
Br
Br
Cl
Cl
OH
OH
NH2
NH2
Br
11

10b
1.5
77
OMe
Br
OMe
Br
Br
aisolated yield after chromatographic purification
b reaction time is 2 hours
12

Table 3 Bromination of anilines using TsNBr2
Entry
Substrate(a)
TsNBr2(e Product(b)
quiv)
Yielda(
%)
NH2
NH2
11
1.5
90
Br
Br
Br
Br
Br
NH2
NH2
12
13
14
1
1
1
92
90
88
Br
Br
Br
NH2
NH2
Br
CH3
NH2
CH3
NH2
Br
Br
Br
NO2
NH2
NO2
NH2
Br
15
1
90
Br
Br
aIsolated yield after chromatographic purification.
13

Scheme 1 Bromination of aromatics using TsNBr2
14