A simple and regioselective α-bromination of alkyl aromatic compounds by two-phase electrolysis

Article abstract of DOI:10.1016/j.tetlet.2005.08.044

Electrochemical bromination of toluene and substituted toluenes by two-phase electrolysis yields the corresponding α-brominated products. The reaction has been carried out in a single compartment cell with platinum electrodes at 0°C in chloroform using an aqueous sodium bromide solution (60%) containing a catalytic amount of HBr. Two-phase electrolysis results in high yields (60-95%) of monobromo compounds with very high regioselectivity (>95%).

Full text of DOI:10.1016/j.tetlet.2005.08.044

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7047–7050
A simple and regioselective a-bromination of alkyl
aromatic compounds by two-phase electrolysis
T. Raju,* K. Kulangiappar, M. Anbu Kulandainathan and A. Muthukumaran
Electroorganic Division, Central Electrochemical Research Institute, Karaikudi 630 006, India
Received 3 June 2005;revised 5 August 2005;accepted 10 August 2005
Abstract—Electrochemical bromination of toluene and substituted toluenes by two-phase electrolysis yields the corresponding
a-brominated products. The reaction has been carried out in a single compartment cell with platinum electrodes at 0 ꢀC in chloro-
form using an aqueous sodium bromide solution (60%) containing a catalytic amount of HBr. Two-phase electrolysis results in high
yields (60–95%) of monobromo compounds with very high regioselectivity (>95%).
ꢁ 2005 Elsevier Ltd. All rights reserved.
Substitution of C–H bonds in alkyl aromatic com-
pounds by radical halogenation is one of the most
important reactions for functionalisation of alkyl aro-
matics. Benzyl bromides and substituted benzyl bro-
mides are primarily used as synthetic intermediates in
the pharmaceutical and other fine chemical industries.
products. In a two-phase electrolysis system, the reactive
species formed by the electrolytic oxidation of a halide
ion in the aqueous phase can be taken continuously into
the organic layer and then reacted with the substrate to
give the products regioselectively. After the completion
of the electrolysis, separation and concentration of the
organic layer affords the product.
Radical bromination on benzylic positions has been
achieved using bromine1–3 and N-bromosuccinimide.4,5
In addition, the bromine complex of the styrene vinyl-
pyridine co-polymer6 and bromotrichloroethane7,8 and
copper(II) bromide9 have been reported to be effective
for benzylic bromination. The majority of brominating
agents require the presence of a peroxide or another rad-
ical initiator. Side-chain bromination using sodium bro-
mate and bromotrimethylsilane has also been reported10
but in only low yields. By using electrochemical technol-
ogy, it is possible to carry out a desired reaction via a
two-phase electrolytic reaction, resulting in high yields
and selectivity.
Electrochemical bromination has been investigated in dif-
ferent solvents12–19 and most of the work deals with ring
brominated products. Side-chain bromination has not
been much explored. In continuation of our earlier work
on electrochemical halogenation of aromatic com-
pounds, we present a simple and regioselective electro-
chemical method for the a-bromination of toluene and
substituted toluenes to give the corresponding benzyl bro-
mides in very good yields by two-phase electrolysis20 at
0 ꢀC in a single compartment cell as shown in Scheme 1.
We observed smooth bromination at the a-position of
the side-chain without the formation of any poly-bromi-
nated product. A number of alkyl aromatics and substi-
tuted alkyl aromatic compounds were subjected to
side-chain bromination by two-phase electrolysis
using an aqueous 60% NaBr solution as the supporting
Two-phase electrolysis has a distinct advantage over
conventional homogeneous electrolysis in practical elec-
tro-organic synthesis.11 In the homogeneous system, less
selectivity is observed due to oxidation of the substrate
on the surface of the electrode giving mixtures of nuclear
(ortho and para isomers) and side-chain brominated
CH2Br
CH3
Pt/Pt, NaBr+CHCl3
0 oC
Keywords: Electrochemical bromination;Two-phase electrolysis;
a-Brominated products;Regioselectivity.
Corresponding author. Tel.: +91 04565 227772;fax: +91 04565
*
Scheme 1. Electrochemical bromination of toluene by two-phase
electrolysis.
227713;e-mail: rajuorganic@yahoo.co.in
0040-4039/$ - see front matter ꢁ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.044

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T. Raju et al. / Tetrahedron Letters 46 (2005) 7047–7050
Table 1. The ratio of reactants and products of the electrochemical bromination of toluene, substituted toluenes and substituted naphthalenes via
two-phase electrolysis
Entry
1
Reactant
Product
Charge passed (F/mol)
4.5
Yield (%)
91
Current efficiency (%)
44
CH3
CH2Br
CH3
CH2Br
2
3
5.0
3.0
90
89
40
44
Cl
Cl
CH3
CH2Br
Br
Br
CH2CH3
CH(Br)CH3
4
5
4.5
3.0
85
62
37
25
CH3
Cl
CH2Br
CH2Br
Cl
CH3
Cl
Cl
6
7
4.0
3.0
6.0
9.0
57a
35
33
32
41
Cl
Cl
CH3
CH2Br
50
CH3
CH3
CH2Br
48b
CH2Br
CH2Br
90
CH2Br
CH2Br
CH3
8
9
6.0
6.0
12c
80
5
OMe
OMe
Br
CH3
CH3
26
a Benzal bromide 22% formed along with 10% recovered starting material.
b 4-Methylbenzyl bromide 45% formed along with 2% recovered starting material.
c 3-Bromo-4-methoxytoluene 39% and 2-bromo-4-methoxytoluene 37% were formed together with 12% recovered starting material.

T. Raju et al. / Tetrahedron Letters 46 (2005) 7047–7050
7049
electrolyte containing a catalytic amount of HBr (5%).
The product distributions from the reactions are listed
in Table 1. The reaction proceeds under mild conditions
and in an efficient way in the presence of a less hazardous
brominating agent than Br2, N-bromosuccinimide and
pyridinium tribromide. In contrast to the exclusive benz-
ylic bromination of alkyl benzenes, an alkyl naphthalene
was brominated mainly on the ring. 2-Methylnaphthal-
ene, for example, gave 1-bromo-2-methylnaphthalene as
the only isolated brominated product.
alternative procedure. Studies were carried out on the
electrochemical synthesis of benzyl bromide and substi-
tuted benzyl bromides [a-brominated products] from
substituted toluenes in high yields. Reactions were carried
out under mild conditions using very simple electrochem-
ical apparatus. This method has several advantages such
as the absence of secondary products, low cost, selective
bromination, high rate of conversion and high yields.
References and notes
Side-chain bromination of toluene follows a free radical
mechanism and the brominating species is dibromine
monoxide (Br2O), which is formed as shown in Eqs. 1
and 2. In the first step, electrochemically generated
bromine is combined with water giving hypobromous
acid and hydrogen bromide. In presence of HBr, one
molecule of water is removed from two molecules of
hypobromous acid as a hydronium ion resulting in the
formation of Br2O as the brominating species, which
is extracted by the organic phase, where the selective
bromination occurs.
1. Coleman, G. H.;Honeywell, G. E. Org. Synth. 1943, Coll.
Vol. 2, 443.
2. Snell, J. M.;Weissberger, A. Org. Synth. 1955, Coll. Vol.
3, 788.
3. Stephenson, F. M. Org. Synth. 1963, Coll. Vol. 4, 984.
4. Pizey, J. S. In Synthetic Reagents;Halsted Press: New
York, 1974;Vol. 2, pp 1–63.
5. Campaign, E.;Tuller, B. F. Org. Synth. 1963, Coll. Vol. 4,
921.
6. Sket, B.;Zupan, M. J. Org. Chem. 1986, 51, 929.
7. Huyser, F. J. Am. Chem. Soc. 1960, 82, 391.
8. Baldwin, S. W.;O Õ Neil, T. H. Synth. Commun. 1976, 6,
109.
9. Chaintreau, A.;Adrian, G.;Couturier, D. Synth. Com-
mun. 1981, 11, 669.
10. Lee, J. G.;Cha, H. T.;Yoon, U. C.;Suh, Y. S.;Kim, K.
C.;Park, J. S. Bull. Kor. Chem. Soc. 1991, 1, 4.
11. Forsyth S. R.;Pletcher, D. Extended Abstracts of the Ist
International Symposium on Electroorganic Synthesis,
Kurashiki;1986;p 35.
12. Casalbore, G.;Mastragostino, M.;Valcher, S. J. Electro-
anal. Chem. 1975, 61, 33.
13. Casalbore, G.;Mastragostino, M.;Valcher, S. J. Electro-
anal. Chem. 1976, 68, 123.
14. Casalbore, G.;Mastragostino, M.;Valcher, S. J. Electro-
anal. Chem. 1977, 77, 373.
15. Mastragostino, M.;Valcher, S.;Lazzari, P. J. Electroanal.
Chem. 1981, 126, 189.
16. Mastragostino, M.;Valcher, S.;Biserni, M. J. Electroanal.
Chem. 1983, 158, 369.
17. Nematollahi, D.;Akaberi, N. Molecules 2001, 6, 639.
18. Nematollahi, D.;Akaberi, N. J. Electroanal. Chem. 2000,
481, 208.
Br2 + H2O ! HOBr + HBr
ð1Þ
2HOBr ! Br2O + H2O
ð2Þ
As the reactive species Br2OÅ is unstable, it is cleaved
homolytically into BrÅ and OBr. The more reactive
ÅOBr, abstracts a benzylic hydrogen to form HOBr. Sub-
sequently, the bromine radical attacks the benzyl radical
and benzyl bromide is formed as the product. This
explains the fact that the isolated product is only benzyl
bromide. Although dibromine monoxide is exception-
ally reactive in the bromination of non-activated and
deactivated alkyl aromatic compounds, an activated
compound like 4-methoxytoluene gives a higher percent-
age of nuclear brominated product rather than side-
chain brominated products (entry 7 in Table 1). This is
due to ring bromination of activated aromatics by the
attack of Br+, which is generated from HOBr as shown
in Eq. 3.
19. Ogamino, T.;Mori, K.;Yamamura, S.;Nishiyama, S.
Electrochim. Acta 2004, 49, 4865.
HOBr + Hþ ! H2O + Brþ
ð3Þ
20. Representative electrochemical procedure: Deionised
water was used for preparing sodium bromide solution.
An Aplab power source was used as the direct current
source for the electrolysis. A beaker type glass cell (120 ml
capacity) equipped with a magnetic stirrer was used for the
electrolysis and two platinum sheets of 10 cm2 area were
used as the anode and the cathode. Fifty milliliters of 60%
sodium bromide solution containing a catalytic amount of
hydrobromic acid (5%) was used as the electrolyte and the
bromine source. The reaction was monitored by HPLC
using a Shimpack ODS-18 column (125 mm · 4.5 mm) as
the stationary phase. The eluent consisted of methanol/
water (70:30) at a flow rate of 1 ml/min. Samples were
analysed at a wavelength of 254 nm with a UV detector.
Authentic samples of benzyl bromide and substituted
benzyl bromides were used to calculate the peak areas of
the corresponding experimental products for yield calcu-
lation.
If HOBr alone was present as the brominating agent in
the absence of HBr, then the product obtained from tol-
uene was a mixture of side-chain brominated (54%) and
nuclear brominated (47%) products [a mixture of 22% o-
bromotoluene and 25% p-bromotoluene]. The formation
of these products was confirmed by chemically generat-
ing HOBr as in Eq. 4;the toluene being brominated by
the usual method.
HgO + 2Br2 + H2O ! 2HOBr + HgBr2
ð4Þ
Furthermore, dibromine monoxide was prepared chem-
ically in CCl4 as shown in Eq. 5 and toluene was bromi-
nated at 0 ꢀC. The product obtained was benzyl bromide
as the sole product.
HgO + 2Br2 ! Br2O + HgBr2
ð5Þ
In conclusion, the electrochemical method for side-chain
bromination of toluene to yield benzyl bromide by two-
phase electrolysis constitutes a novel and an efficient
Toluene (610 mg, 6.6 mmol) was dissolved in chloroform
(25 ml) and the solution was transferred to a single
compartment electrolytic cell. A 60% solution of aqueous

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T. Raju et al. / Tetrahedron Letters 46 (2005) 7047–7050
NaBr (50 ml) containing 5% HBr was added. The aqueous
at a current density of 30 mA/cm2 until the quantity of the
current indicated in Table 1 was passed. An aliquot was
drawn periodically from the organic phase and analysed
by HPLC. After the completion of the electrolysis, the
lower organic phase was separated;washed with water
(2 · 25 ml), dried over anhydrous Na2SO4 and the solvent
was removed by distillation. HPLC analysis of the residue
indicated the presence of 91% benzyl bromide and 5%
nuclear brominated toluene along with 4% unconverted
toluene.
upper phase acted as the supporting electrolyte and also as
the bromine source. Two platinum electrodes were placed
in the aqueous phase without touching the organic phase
but very close to the interphase. The organic phase alone
was stirred with a magnetic stirrer at a rate of 40 rpm in
such a way that the organic layer does not touch the
electrodes. The temperature of the electrochemical cell
contents was monitored at 0–2 ꢀC throughout the elec-
trolysis. The electrolysis was conducted galvanostatically