Highly selective catalytic Friedel-Crafts sulfonylation of aromatic compounds using a FeCl3-based ionic liquid

Article abstract of DOI:10.1016/j.tetlet.2008.04.051

Friedel-Crafts sulfonylation of aromatic compounds was carried out using FeCl₃-based ionic liquid. These liquids serve as efficient media as well as Lewis acid catalyst.

Full text of DOI:10.1016/j.tetlet.2008.04.051

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3931–3934
Highly selective catalytic Friedel–Crafts sulfonylation
of aromatic compounds using a FeCl3-based ionic liquid
Kiumars Bahrami *, Mohammad Mehdi Khodei *, Fomeida Shahbazi
Department of Chemistry, Razi University, Kermanshah 67149, Iran
Nanoscience and Nanotechnology Research Center (NNRC), Razi University, Kermanshah 67149, Iran
Received 20 February 2008; revised 21 March 2008; accepted 9 April 2008
Available online 12 April 2008
Abstract
Friedel–Crafts sulfonylation of aromatic compounds was carried out using FeCl3-based ionic liquid. These liquids serve as efficient
media as well as Lewis acid catalyst.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Friedel–Crafts sulfonylation; Lewis acid; Ionic liquid; Aromatic compounds
1. Introduction
tedious work-up, long reaction times, a need for large
amounts of catalyst, lower selectivity for para/ortho sulf-
onylated isomers, incompatibility with other functional
groups and generation of environmentally hazardous waste
materials, as a result of aqueous extraction procedures.
Also, some of these catalysts are expensive and are not
commercially available. Therefore, there is still a consider-
able interest in investigating other convenient and chemo-
selective synthetic methods for the sulfonylation of
aromatic compounds without using organic solvents, in
terms of economic benefit, environmental impact and
safety.
The wide use of organosulfones as versatile synthons in
organic synthesis is well known.1 Organosulfones are useful
intermediates in a wide range of fields such as agrochemi-
cals,2 pharmaceuticals3,4 and polymers.5 The most practical
laboratory method for preparing aryl sulfones is via the
Friedel–Crafts sulfonylation of arenes using sulfonyl
chlorides.6,7 Catalysts such as AlCl3 and SbF5,8 BiCl3/
triflic acid,9 metal-exchanged K-10 Montmorillonites,10
Sn(OTf)2,11 In(OTf)3,12 Nafion-H,13 Zn-exchanged zeo-
lites14 and InCl3/triflic acid15 have been used to promote
Friedel–Crafts reactions.
The design of solvent-free reactions and the use of ionic
liquids in organic synthesis have gained significant inter-
est.16 Some of the unique physical and chemical properties
A large number of these catalysts suffer from drawbacks
such as difficult handling, harsh reaction conditions,
_
+
O
S
)3FeCl4
N(
Ph
+
R = Me-, H-
Ar
Ar
H
R
SO2Cl
R
60 oC
Scheme 1.
O
*
Corresponding authors. Fax: +98 831 4274559 (K.B.).
E-mail addresses: kbahrami2@hotmail.com (K. Bahrami), mmkhoda@razi.ac.ir (M. M. Khodei).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.051

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K. Bahrami et al. / Tetrahedron Letters 49 (2008) 3931–3934
Table 1
of ionic liquids such as thermal stability, negligible vapour
pressure, ability to dissolve a large range of organic and
inorganic compounds, increased reaction rate, selectivity
and tendency to immobilize starting materials and catalysts
make them an attractive substitute for various volatile
organic solvents.
Many organic transformations have been carried out in
ionic liquids, for example, hydrogenation,17,18 oxidation,19
epoxidation20 and hydroformylation21 reactions.
In continuation of our recent work on sulfonylation
reactions,22 we report a FeCl3-based ionic liquid as an
effective and a highly chemoselective catalyst for the Fri-
edel–Crafts sulfonylation of aromatic compounds under
mild reaction conditions (Scheme 1).
Effect of increasing the amount of FeCl3 on the sulfonylation reaction of
bromobenzene, using [BTBA]Cl–FeCl3 ionic liquida
[BTBA]Cl/[FeCl3]
Mole fraction of FeCl3 (N)
Yieldb (%)
1:0.1
1:0.3
1:0.5
1:0.7
1:1
0.09
0.23
0.33
0.41
0.5
30
40
60
50
90
a
Reaction conditions: The reactions were performed with 4-meth-
ylbenzenesulfonyl chloride (1 mmol), bromobenzene (1 mmol) and ionic
liquid (1 mmol) for 5 min, at 60 °C.
b
Isolated yield.
To study the effect of increasing the amount of the Lewis
acid in the ionic liquid, the sulfonylation of bromobenzene
as a model substrate, with 4-methylbenzenesulfonyl chlo-
ride was carried out in benzyl tributylammonium chloride
(BTBAC) at 60 °C. The best result based on yield and time
of the reaction was obtained with [BTBA]Cl–FeCl3,23
N = 0.5 (Table 1).
Table 2
Sulfonylation of bromobenzene with 4-methylbenzenesulfonyl chloride in
the presence of several Lewis acids in [BTBA]Cl–Lewis acid, N = 0.5
Entry
[BTBA]Cl–Lewis acid
Time (min)
Yielda (%)
1
2
3
4
a
[BTBA]Cl–ZrCl4
[BTBA]Cl–ZnCl2
[BTBA]Cl–AlCl3
[BTBA]Cl–FeCl3
5
5
5
5
Trace
Trace
30
90
We also investigated the sulfonylation of bromobenzene
with 4-methyl benzenesulfonyl chloride in the presence of
Isolated yields.
Table 3
Sulfonylation of aromatic compounds using [BTBA]Cl–FeCl3 ionic liquid (N = 0.5), with benzenesulfonyl chloride and 4-methylbenzenesulfonyl chloride
Entry
Substrate
R
Time (min)
Producta
Yieldb (%) [o:m:p]
Me
Me
O
1
Me
1
96
Me
S
Me
Me
O
Me
Me
Me
Me
O
S
2
3
4
5
6
H
<1
1
94
97
95
94
93
Me
Me
Me
Me
O
Me
Me
Me
O
S
Me
Me
H
O
Me
Me
O
S
Me
Me
Me
1
Me
Me
O
O
S
Me
H
1
Me
Me
O
Me
Me
O
S
1
Me
Me
O
Me
Me
Me
Me
Me
O
7
Me
1
93 [5:0:95]
S
Me
O

K. Bahrami et al. / Tetrahedron Letters 49 (2008) 3931–3934
3933
Table 3 (continued)
Entry
Substrate
R
H
Time (min)
1
Producta
Yieldb (%) [o:m:p]
Me
Me
O
S
8
91 [5:0:95]
Me
Me
Me
Me
O
O
Me
9
10
11
12
13
14
15
16
17
18
Me
H
2
2
1
1
3
3
4
4
5
5
90 [5:0:95]
92 [5:0:95]
95 [15:0:85]
93 [13:0:87]
92
S
Me
O
O
S
Me
O
O
MeO
MeO
Me
H
S
Me
MeO
MeO
O
O
S
O
O
S
Me
H
Me
O
O
S
93
O
O
Br
Br
Cl
Cl
Me
H
90 [5:0:95]
90 [5:0:95]
91 [5:0:95]
90 [5:0:95]
S
Me
Br
Br
Cl
Cl
O
O
S
O
O
S
Me
H
Me
Me
O
O
S
O
O
19
20
Me
H
3
3
91 [a = 8,b = 92]c
90 [a = 6, b = 94]c
S
O
O
S
O
21
NO2
60
No reaction
—
Me
Me
a
The products were characterized by comparison of their spectroscopic data with those reported in the literature.24–27
Isolated yields.
Isomers distribution based on 1H NMR.
b
c
several Lewis acids in [BTBA]Cl–Lewis acid, N = 0.5. The
p-toluenesulfonyl chloride and benzenesulfonyl chloride
under the optimized reaction conditions (Table 3). It was
observed that the presence of electron-donating groups
such as alkyl and OMe on the aromatic compound gave
results showed that only FeCl3 was effective (Table 2).
To extend the scope of the procedure, we investigated
the reactions of a series of aromatic hydrocarbons with

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K. Bahrami et al. / Tetrahedron Letters 49 (2008) 3931–3934
Table 4
Acknowledgement
Comparison of the sulfonylation of methoxybenzene using [BTBA]Cl–
FeCl3 with methods reported in the literature
The authors are thankful to the Razi University
Research Council for financial support for this research.
Conditions
Yield (%)
[o:m:p]
[BTBA]Cl–FeCl3/4-MePhSO2Cl/60 °C/1 min
[BTBA]Cl–FeCl3/PhSO2Cl/60 °C/1 min
Crosslinked polystyrene supported AlCl3 (Ps-AlCl3)/4-
MePhSO2Cl/85 °C/1.1 h28
95 [3:0:97]
93 [3:0:97]
92 [9:3:88]
References and notes
1. (a) Tanaka, K.; Kaji, A. Synthetic Uses of Sulfones. In Synthetic Uses
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Field, L. Synthesis 1978, 713.
BiCI3–TfOH/PhSO2Cl/120 °C/0.5 h29
Indium metal/4-MePhSO2Cl/dioxane/100 °C30
Fe-pillared bentonite (Fe-PILC)/4-MePhSO2Cl/120 °C/
20 min27
82 [47:0:53]
76
84
[35.2:0:64.8]
84 [43:0:57]
[bmim]ClÁFeCl3/4-MePhSO2Cl/50 °C/5 h31
2. Michaely, W. J.; Kraatz, G. W. U.S. Patent 4,780,127, 1988 (CAN:
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excellent yields of the products (entries 10 and 11). Also,
deactivated arenes such as chlorobenzene and bromoben-
zene underwent sulfonylation in excellent yields (entries
16 and 17). Further, an improvement in the regioselectivity
was observed in the sulfonylation of naphthalene with ben-
zenesulfonyl chloride and 4-methylbenzenesulfonyl chlo-
ride (entries 19 and 20). 4-Nitrobenzenesulfonyl chloride
failed to give the sulfonylated product (entry 21). As shown
in Table 3, a significant enhancement of para selectivity was
observed in each case.
To access the feasibility of applying this method in a
preparative scale, we carried out the sulfonylation of mesit-
ylene with benzenesulfonyl chloride in 40 mmol scale. As
expected, the reaction proceeded smoothly, similar to the
case in a smaller scale (Table 3, entry 2), and the desired
aryl sulfone was obtained in 96% isolated yield.
In order to show the efficiency of this method, the results
of the sulfonylation of methoxybenzene with sulfonylating
agents using our method are compared with those reported
by other methods. The results show that this method is
superior to some previously reported methods in terms of
yields, reaction times and the amount of the reagent used
for successful sulfonylation (Table 4).
In conclusion, the best results are realized and the utility
of the FeCl3-based ionic liquid both as solvent and catalyst
is satisfactorily justified. The advantages of this methodol-
ogy using a FeCl3-based ionic liquid are mild reaction
conditions, excellent yields, short reaction times, simple
work-up procedure, low cost and easy preparation and
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tributyl ammonium chloride (311.94 mg, 1 mmol) with FeCl3 (162.2
mg, 1 mmol) for 2 min; mp = 57–59 °C.
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2. General procedure for sulfonylation
To [BTBA]Cl–FeCl3 (N = 0.5, 1 mmol), p-toluenesulf-
onyl chloride or benzenesulfonyl chloride (1 mmol) and
aromatic compound (1 mmol) were added. The reaction
mixture was stirred magnetically, at 60 °C. After complete
conversion, as indicated by TLC, the reaction mixture was
quenched by adding water (10 mL), extracted with diethyl
ether (4 Â 10 mL) and the extract dried with anhydrous
MgSO4. The filtrate was evaporated and the corresponding
sulfone was obtained in excellent yield (Table 3).
27. Singh, D. U.; Singh, P. R.; Samant, S. D. Tetrahedron Lett. 2004, 45,
9079.
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´
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