Green, mild and efficient bromination of aromatic compounds by HBr promoted by trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane in water as a solvent

Article abstract of DOI:10.1016/j.cclet.2012.01.009

A combination of HBr and trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane as a new and powerful oxidant was found effective for facile bromination of different aromatic compounds at room temperature in water as a green solvent. Mild reaction conditions, high selectivity and yield, high reaction rate and non-toxicity are some of the major advantages of this synthetic protocol.

Full text of DOI:10.1016/j.cclet.2012.01.009

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 387–390
www.elsevier.com/locate/cclet
Green, mild and efficient bromination of aromatic compounds by
HBr promoted by trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-
dioxolane in water as a solvent
b
Kaveh Khosravi a, , Samira Kazemi
*
a Department of Chemistry, Faculty of Science, University of Arak, Arak, Iran
b Department of Chemistry, Shahr-e-Rey branch, Islamic Azad University, Tehran, Iran
Received 9 October 2011
Available online 3 March 2012
Abstract
AcombinationofHBrandtrans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolaneasanewandpowerfuloxidantwasfoundeffective
for facile bromination of different aromatic compounds at room temperature in water as a green solvent. Mild reaction conditions, high
selectivity and yield, high reaction rate and non-toxicity are some of the major advantages of this synthetic protocol.
# 2012 Kaveh Khosravi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane; HBr; Bromination; Anilines; Phenoles
The bromination of aromatic substrates is very important and is an interesting deal in organic chemistry because of
the commercial importance of brominated compounds in synthesis of natural products and biological active
compounds such as potent antitumor, antibacterial, antifungal, antiviral and anti oxidizing agents [1]. Unfortunately,
reported conventional aromatic bromination methods that have used toxic elemental bromine or hazardous acidic
reagents, generate toxic, corrosive and environmental pollutant wastes [2]. Examples of these methods include: Br2–
Lewis acids [3], NBS–H2SO4–CF3CO2H [4], NBS–PTSA [5], NBS–NaOH [6], NBS–SiO2 [7], Br2–Al2O3 [8], Br2–
Zeolite [9], NBS–Amberlyst [10], NBS–HZSM-5 [11], Clayzib [12], tert-BUOOH- or H2O2–HBr [13], HBr–DMSO
[14], Br2–SO2Cl2 [15], N,N,N,N-tetrabromobenzen-1,3-disulfonylamide [16], hexamethylenetetramin–2Br2 [17],
KBr–benzyltriphenylphosphonium peroxymonosulfate [18], NBS–Al2O3 [19], NBS–NH4OAc [20], NBS–TEAB
[21], NBS–Pd(OAc)2 [22], NBS–DMF (or THF) [23], CuBr2 [24], alkylpyridinium tribromide [25], tribromoiso-
cyanouric acid [26], bromodichloroisocyanuric acid [27], polymer-supported organotin reagents [28], NH4VO3–
H2O2–HBr [29], [Bmim]Br3 [30], NBS–CCl4 [37], poly(diallyldimethylammonium tribromide [38], etc. Replacement
of such reagents with non-toxic, inexpensive, available and more selective reagents is very interesting and still
represents an important goal in the context of clean synthesis. Recently, synthesis of gem-dihydroperoxides and their
applications as affective oxidants have been reported [31]. Newly, we have reported the synthesis of trans-3,5-
dihydroperoxy-3,5-dimethyl-1,2-dioxolane and its applications as new, solid and affective oxidant [32]. In this work,
* Corresponding author.
E-mail address: khosravi.kaveh@gmail.com (K. Khosravi).
1001-8417/$ – see front matter # 2012 Kaveh Khosravi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2012.01.009

388
K. Khosravi, S. Kazemi / Chinese Chemical Letters 23 (2012) 387–390
G
G
O O
Me
HOO
OOH
Me
/ HBr
(Br)n
R'
water / rt
R
R'
n = 1, 2, 3
R
G = OH, OMe, NH2, NMe2
R = H, Br, Cl, Me, NO2, CN
R' = H, Br, Cl, Me
Scheme 1.
we have used trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane for in situ generation of Br+ from HBr and we wish
to report the bromination of aromatic substrates by this system in green and mild condition with excellent yields
(Scheme 1). In order to establish the conditions of the titled reactions, we initially examined the bromination of phenol
(1 mmol) as test compound. The effects of solvent and oxidant were studied using different solvents such as CH2Cl2,
CHCl3, CCl4, MeCN, and water under various amounts of oxidant. It was noticed that, the best results for
monobromination (93%, Table 2, entry 1), dibromination (93%, Table 2, entry 2) and tribromination (91%, Table 2,
entry 3) using respectively 1.1, 2.2 and 3.5 mmol of HBr were obtained when the reactions were conducted under
stirring at room temperature in water as the solvent of choice. To develop the scope of these reactions, several other
aromatic substrates were subjected to bromination under the optimized conditions. The experimental results are
summarized in Table 2. As shown in Table 2, the phenols and also the anilines with both electron-withdrawing groups
and electron-releasing groups are brominated by this method. As is anticipated for electrophilic substitutions, the
electron-withdrawing groups decrease the rate of reaction (7, 8, 9, 16, 17, 22, and 23 entries) and the electron-releasing
groups increase the rate of reaction (10, 13, 14, 15, and 18 entries). Also, three-bromination and di-bromination is
more slow than mono-bromination because of steric hindrance of Br atoms.
Trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane is a solid, powerful, non-toxic, inexpensive and effective
oxidant that is synthesized easily [32] and seems that it can eliminate the defects of hydrogen peroxides (such as
problems of weighing, weak power in organic liquids, having the water, needing catalyst, etc.). So, we have used it for
in situ generation of Br+ from HBr as an effective electrophilic space. Then, this generated Br+ attack to aromatic ring
and finally, after losing H+, the aromaticity of ring will obtain again (Scheme 2). The results of this methodology are
compared with other brominating methods in Table 1. Clearly, the reaction times and yields by this method are notable
in compare with other bromination methods.
In summary, trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane has been conveniently used as an efficient and
high potent oxidant for in situ generation of Br+ ion in reaction with HBr. This ion can subsequently act as reactive
electrophiles towards the aromatic substrates to afford the corresponding brominated products in quantitative yields.
The reactions proceed under mild conditions at room temperature with a simple work up procedure. This protocol is
green and considered as environmentally benign since no toxic residues or corrosive acids are introduced to the
environment.
Chemicals used in this work were purchased from Fluka and Merk chemical companies and used without
purification. IR spectra were recorded on a PerkinElmer GX FT IR spectrometer from KBr pellets. 1H and 13C NMR
Table 1
Reaction times and yield for previously published methods.
Substrate
Product
Condition
Time (h)
Yield (%)
Ref.
C6H5OH
C6H5OH
C6H5OH
C6H5OH
C6H5OH
C6H5OH
C6H5NH2
C6H5NH2
C6H5NH2
C6H5NH2
C6H5NH2
4-BrC6H4OH
4-BrC6H4OH
4-BrC6H4OH
4-BrC6H4OH
4-BrC6H4OH
4-BrC6H4OH
4-BrC6H4NH2
4-BrC6H4NH2
4-BrC6H4NH2
4-BrC6H4NH2
4-BrC6H4NH2
This method
0.4
1.5
5
93
45
88
82
58
94
84
82
85
66
86
–
[17]
[18]
[33]
[34]
[35]
–
˚
Hexamethylenetetramine–bromine, À15 C
PhCH2Ph3PHSO5/KBr
˚
ZrBr4/diazene mixture, 0 C, argon
0.67
5
Potassium bromide and hydrogen peroxide over zeolites
Heteropoly acid cesium salt/cetyltrimethylammonium bromide/Br2
This method
15+ Im
0.2
0.5
0.75
6
Tetrabutylammonium Bromide Promoted by V2O5–H2O2
˚
[2]
Hexamethylenetetramine–bromine, À15 C
[17]
[33]
[36]
˚
ZrBr4/diazene mixture, 0 C, argon
Tetrabutylammonium peroxydisulfate
1

K. Khosravi, S. Kazemi / Chinese Chemical Letters 23 (2012) 387–390
389
-
Br
HO
O
O
-
O
O
O
+
O
H Br
Me
HOO
O OH
Me
H2O2
+
Me
+ BrOH
Me
- BrOH
Me
Me
HOO
1
H2O2 + HBr
Br - OH
BrOH + H2O
+
-H
H
ArBr
Scheme 2.
ArH
Ar
Br
spectra were measured for samples in CDCl3 with a JEOL FX 90Q instrument at 90 and 22.5 MHz respectively, using
Me4Si as internal standard. Melting points were measured on a SMPI apparatus.
Caution: Although we did not encounter any problem with peroxides, peroxides are potentially explosive and
should be handled with precautions; all reactions should be carried out behind a safety shield inside a fume hood and
transition metal salts or heating should be avoided.
General procedure for bromination of aromatic substrates: To a mixture of aromatic substrate (1 mmol) and
appropriate amount of HBr (47%) (Table 2) in water (4 mL) was added, corresponding amount of trans-3,5-
dihydroperoxy-3,5-dimethyl-1,2-dioxolane (Table 2) and the mixture was stirred at room temperature for an
appropriate time (Table 2). After completion of the reaction as monitored by TLC (n-hexane/EtOAc; 2:1), 1 mol/L
aqueous solution of Na2SO3 (3 mL) was added to quench the reaction and stirring was continued further for a 10 min.
Then, the reaction mixture was diluted with distilled water (15 mL) and then the products were extracted by CHCl3
(3 Â 5 mL). The mixture of organic layers was dried by MgSO4 and the solvent evaporated to obtain pure product. For
di-bromination reactions use of excess amounts of HBr and oxidant are required (Table 2). All the products were
Table 2
Bromination of aromatic substrates with HBr promoted by trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane at room temperature.a
Entry
Substrate
Product
HBr (mmol)
Time (h)
Yield (%)b
mp (8C)
Found
Reported [18,33]
1
2
C6H5OH
4-BrC6H4OH
1.1
2.2
3.5
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.5
1.3
1
0.4
0.9
1.5
1.2
1
93
93
91
88
92
86
83
80
86
79
75
89
96
96
98
88
87
89
84
93
91
85
86
93
62–64
41–43
88–90
39–41
39–41
88–90
52–54
64–66
68–70
56–58
17–18
32–34
64–66
80–82
232–234
117–119
94–96
56–58
56–58
124–126
124–126
73–75
66–68
110–112
63
40
C6H5OH
2,4-Br2C6H3OH
3
C6H5OH
2,4,6-Br3C6H2OH
2,4-Br2C6H3OH
85–86
40
4
2-BrC6H4OH
4-BrC6H4OH
2,6-Br2C6H3OH
2-ClC6H4OH
2,4-Cl2C6H3OH
2,6-Cl2C6H3OH
3-MeC6H4OH
C6H5OMe
5
2,4-Br2C6H3OH
40
6
2,4,6-Br3C6H2OH
4-Br-2-ClC6H3OH
6-Br-2,4-Cl2C6H2OH
4-Br-2,6-Cl2C6H2OH
4-Br-3-MeC6H3OH
4-BrC6H4OMe
1.6
2.5
3
85–86
55
7
8
62
9
3
66
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
0.8
0.9
3
54
15
4-ClC6H4OH
2-MeC6H4OH
2,6-Me2C6H3OH
2,4-Me2C6H3OH
4-NO2C6H4OH
2-NO2C6H4OH
C6H5NMe2
2-Br-2-ClC6H3OH
4-Br-2-MeC6H3OH
4-Br-2,6-Me2C6H2OH
6-Br-2,4-Me2C6H2OH
2-Br-4-NO2C6H3OH
4-Br-2-NO2C6H3OH
4-BrC6H4NMe2
32–34
63–64
78–79
232
1
1
1.4
4
114–115
91–93
55–56
57–58
121–123
124–126
71–73
64–66
108–110
3
0.2
0.2
0.7
1.4
1.1
1.2
3
C6H5NH2
4-BrC6H4NH2
1
4-BrC6H4NH2
C6H5NH2
2,4,6-Br3C6H2NH2
2,4,6-Br3C6H2NH2
4-Br-2-ClC6H3NH2
2-Br-4-ClC6H3NH2
2-Br-4-CNC6H3NH2
2.2
3.5
1.1
1.1
1.3
2-ClC6H4NH2
4-ClC6H4NH2
4-CNC6H4NH2
a
Conditions: substrate (1 mmol), oxidant (0.5 mmol; 1 mmol for entry 2 and 1.5 mmol for entry 3), room temperature, water as the solvent.
Isolated yields.
b

390
K. Khosravi, S. Kazemi / Chinese Chemical Letters 23 (2012) 387–390
characterized by their physical and spectral (IR, 1H NMR and 13C NMR) analysis and compared with the reported data
[18,33].
References
[1] (a) C. Christophersen, Acta Chem. Scand. 39B (1985) 515;
(b) H.A. Muathen, J. Org. Chem. 57 (1992) 2740;
(c) A. Butler, J.V. Walker, Chem. Rev. 93 (1993) 1937;
(d) Ullmann, Ullmann’s Encyclopedia of Industrial Chemistry 6th ed., Wiley-VCH, Weinheim, 1998.
[2] U. Bora, G. Bose, M.K. Chaudhuri, et al. Org. Lett. 2 (2000) 247.
[3] H. Schmid, Helv. Chim. Acta 29 (1946) 1144.
[4] J. Duan, L.H. Zhang, W.R. Dolbier, Synlett 8 (1999) 1245.
[5] P. Bovonsombat, E. McNelis, Synthesis (1993) 237.
[6] J. Auerbach, S.A. Weissman, T.J. Blacklock, et al. Tetrahedron Lett. 34 (1993) 931.
[7] H. Konishi, K. Aritomi, T. Okano, et al. Bull. Chem. Soc. Jpn. 62 (1989) 591.
[8] B.C. Ranu, D.C. Sarkar, R. Chakraborty, Synth. Commun. 22 (1992) 1095.
[9] (a) F. Vega, Y. Sasson, K. Huddersman, Zeolites 13 (1993) 341;
(b) K. Smith, D. Bahzad, Chem. Commun. 4 (1996) 467.
[10] Y. Goldberg, H. Alper, J. Mol. Catal. 88 (1994) 377.
[11] V. Paul, A. Sudalai, T. Daniel, et al. Tetrahedron Lett. 35 (1994) 7055.
[12] J.H. Clark, J.C. Ross, D.J. Macquarrie, et al. J. Chem. Soc., Chem. Commun. 13 (1997) 1203.
[13] N.B. Barhate, A.S. Gajare, R.D. Wakharkar, et al. Tetrahedron Lett. 39 (1998) 6349.
[14] G. Majetich, R. Hicks, S. Reister, J. Org. Chem. 62 (1997) 4321.
[15] J.M. Gnaim, R.A. Sheldon, Tetrahedron Lett. 46 (2005) 4465.
[16] R. Ghorbani-Vaghei, H. Jalili, Synthesis 7 (2005) 1099.
[17] M.M. Heravi, N. Abdolhosseini, H.A. Oskooie, Tetrahedron Lett. 46 (2005) 8959.
[18] H. Adibi, A.R. Hajipour, M. Hashemi, Tetrahedron Lett. 47 (2007) 1255.
[19] G.K. Imanzadeh, M.R. Zamanloo, H. Eskandari, et al. J. Chem. Res. (S) (2006) 151.
[20] B. Das, K. Venkateswarlu, A. Majhi, et al. J. Mol. Catal. A: Chem. 30 (2007) 267.
[21] N.C. Ganguly, P. De, S. Dutta, Synthesis 7 (2005) 1103.
[22] D. Kalyani, A.R. Dick, W.Q. Anani, et al. Org. Lett. 12 (2006) 2523.
´
[23] D. Pla, F. Albericio, M. Alvarez, Eur. J. Org. Chem. (2007) 1921.
[24] S. Batt, S.K. Nayak, Synth. Commun. 37 (2007) 1687.
[25] J. Salazar, R. Dorta, Synlett 7 (2004) 1318.
[26] L.S. De Almeida, P.M. Esteves, M.C.S. De Mattos, Synthesis 2 (2006) 221.
[27] L.S. De Almeida, P.M. Esteves, M.C.S. De Mattos, Synlett 11 (2007) 1687.
[28] J.-M. Chretien, F. Zammattio, E. Le Grognec, et al. J. Org. Chem. 70 (2005) 2870.
[29] T. Moriuchi, M. Yamaguchi, K. Kikushima, et al. Tetrahedron Lett. 48 (2007) 2667.
[30] Z.G. Lee, Z.C. Chen, Q.G. Zheng, Chin. Chem. Lett. 16 (2005) 1007.
[31] (a) B. Das, B. Veeranjaneyulu, M. Krishnaiah, J. Mol. Catal. A: Chem. 284 (2008) 116;
(b) A. Bunge, H.J. Hamann, J. Liebscher, Tetrahedron Lett. 50 (2009) 524;
(c) A. Bunge, H.J. Hamann, E. McCalmont, et al. Tetrahedron Lett. 50 (2009) 4629;
(d) B. Das, M. Krishnaiah, B. Veeranjaneyulu, et al. Tetrahedron Lett. 48 (2007) 6286;
(e) K. Jakka, J. Liu, C.G. Zhao, Tetrahedron Lett. 48 (2007) 1395;
(f) J. Jon Paul Selvam, V. Suresh, K. Rajesh, et al. Tetrahedron Lett. 49 (2008) 3463;
(g) P. Ghorai, P.H. Dussault, Org. Lett. 10 (2008) 4577;
(h) K. Zmitek, K. Zupan, S. Stavber, et al. J. Org. Chem. 72 (2007) 6534.
[32] (a) D. Azarifar, K. Khosravi, F. Soleimanei, Synthesis 15 (2009) 2553;
(b) D. Azarifar, K. Khosravi, F. Soleimanei, Molecules 15 (2010) 1433;
(c) D. Azarifar, K. Khosravi, Eur. J. Chem. 1 (2010) 15;
(d) D. Aarifar, K. Khosravi, Synlett 18 (2010) 2755;
(e) D. Azarifar, K. Khosravi, Z. Najminejad, Kh. Soleimani, Heterocycles 81 (2010) 2855.
ˇ
[33] T. Stropnik, S. Bombek, M. Kocevar, et al. Tetrahedron Lett. 49 (2008) 1729.
[34] N. Narender, K.V.V. Krishna Mohan, R. Vinod Reddy, J. Mol. Catal. A: Chem. 192 (2003) 73.
[35] H. Firouzabadi, N. Iranpoor, K. Amani, J. Mol. Catal A: Chem. 195 (2003) 289.
[36] M.Y. Park, S.G. Yang, V. Jadhav, Tetrahedron Lett. 45 (2004) 4887.
[37] M. Cheng, Y. Qiu, H. Liu, et al. Chin. J. Org. Chem. 30 (2010) 1737.
[38] H. Mahdavi, Z. Kachoei, Chin. J. Chem. 28 (2010) 2221.