Nafion-H catalysed sulfonylation of aromatics with arene/alkenesulfonic acids for the preparation of sulfones

Article abstract of DOI:10.1039/b104603a

Synthesis of both symmetric and unsymmetric diaryl/aryl alkyl sulfones is easily achieved by Friedel-Crafts type sulfonylation of aromatics with suitable arene- or alkanesulfonic acids in the presence of Nafion-H, a perfluorinated resinsulfonic acid catalyst.

Full text of DOI:10.1039/b104603a

Nafion-H catalysed sulfonylation of aromatics with
arene/alkenesulfonic acids for the preparation of sulfones1a†
George A. Olah,* Thomas Mathew and G. K. Surya Prakash*
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California,
Los Angeles, CA 90089-1661, USA
Received (in Corvallis, OR, USA) 21st May 2001, Accepted 17th July 2001
First published as an Advance Article on the web 16th August 2001
Synthesis of both symmetric and unsymmetric diaryl/aryl
alkyl sulfones is easily achieved by Friedel–Crafts type
sulfonylation of aromatics with suitable arene- or alkane-
sulfonic acids in the presence of Nafion-H, a perfluorinated
resinsulfonic acid catalyst.
Diaryl sulfones are important drugs active against malaria,
leishmaniasis, infections in patients with AIDS and discoid
lupus erythematosus.2–4 Various methods for the synthesis of
sulfones involve the conventional Friedel–Crafts type sulfony-
lation of aromatics using sulfonyl halides,5 oxidation of the
corresponding sulfides,6 reactions of sulfonyl fluorides with
organolithium compounds or Grignard reagents,7 etc. Recently,
effective synthesis of sulfones from aryl trifluoromethyl sulfone
using Grignard reagents and sulfonyl halides and anhydrides
using metal triflates and zeolites as catalysts8 have been
reported. Thus far no convenient synthetic method is available
for the synthesis of sulfones using sulfonic acids directly.
In this communication, we would like to report an efficient
preparation of aromatic sulfones directly from arene- or
The wide use of organosulfones as very versatile synthons in
organic synthesis is well known for the past few decades.1b–d
Scheme 1
Table 1 Nafion-H catalysed sulfonylation of aromatics using sulfonic acids
Sulfonic acid
Substrate
Benzene
Time/h
20
Yield (%)
48
Sulfone
Toluene
20
16
52
82
p-Xylene
m-Xylene
16
20
80
52
Chlorobenzene
Benzene
Toluene
20
20
50
57
p-Xylene
8
78
m-Xylene
8
70
55
Chlorobenzene
20
CH3SO3H
p-Xylene
8
30
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Chem. Commun., 2001, 1696–1697
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b104603a

alkenesulfonic acids with the use of Nafion-H, a solid
perfluorinated resinsulfonic acid polymer as a catalyst. We have
previously found that Friedel–Crafts type intramolecular acyla-
tion with suitably ortho substituted benzoic acids in the
presence of Nafion-H affords ketones in good yields.9 Nafion
membranes have also been found to allow permeation of
sulfonating reagents such as SO3 and 20% oleum during
sulfonation reactions.10 Preparation of aromatic symmetric and
unsymmetric sulfones could be achieved in good yields
(30–80%) by intermolecular Friedel–Crafts type sulfonylation
of arenes with suitable sulfonic acids (Scheme 1).
Nafion-H has been found to be a suitable solid acid catalyst
with high selectivity and catalytic activity giving good yields of
sulfones. The reaction with the use of Nafion-H conveniently
eliminates the use of volatile or noxious reagents. After the
reactions with Nafion-H, the catalyst is easily regenerated.11
This solid resin catalyst is more convenient and environmen-
tally friendly in comparison with corrosive acid catalysts (liquid
acids) generally used in reactions involving strong acids.
The sulfonylation reactions were carried out by refluxing a
stirred mixture of the corresponding arene- or alkanesulfonic
acid and excess arene in the presence of the solid Nafion-H
catalyst. The arenes act as both the substrate and the solvent.
The products were isolated after filtering the reaction mixture
and distilling off the excess arene.12
The sulfonylation reactions are general for sulfonic acids
such as benzenesulfonic acid, toluenesulfonic acid and metha-
nesulfonic acid. Activated aromatics such as p-xylene and m-
xylene afforded the corresponding sulfones in good yields
( ~ 80%). The yield of the corresponding sulfones from benzene
and toluene were, however, low (5–15%) due to the insufficient
activation of Nafion-H under the used relatively mild refluxing
conditions. On the other hand, when the reactions with benzene
and toluene were conducted under pressure at 160–165 °C, the
product yields increased considerably (48–57%). Along with
the product and the unreacted starting material, minor amounts
of side products due to alkylation and dealkylation were also
observed.
Support of our work by Loker Hydrocarbon Research
Institute is gratefully acknowledged.
Notes and references
† Dedicated to our colleague, Professor William P. Weber on the occasion
of his sixtieth birthday.
1 (a) Considered as catalysis by solid super acids, Part 34. For Part 33, see
ref. 9; (b) K. Tanaka and A. Kaji, Synthetic Uses of Sulfones in The
Chemistry of Sulphones and Sulphoxides, Eds. S. Patai, Z. Rappoport
and C. J. M. Stirling, Wiley-Interscience, New York, 1988, ch. 15, pp.
759; (c) B. M. Trost, Bull. Chem. Soc. Jpn., 1988, 61, 107; (d) L. Field,
Synthesis, 1978, 713.
2 R. C. Hastings and S. G. Franzblau, Ann. Rev. Pharmacol. Toxicol.,
1966, 28, 231.
3 G. Wozel, Int. J. Dermatol., 1989, 28, 17.
4 J. S. Lo, R. E. Berg and K. J. Tomecki, Int. J. Dermatol., 1989, 28,
497.
5 J. B. Hendrickson and K. W. Bair, J. Org. Chem., 1977, 42, 3875; G. A.
Olah and H. C. Lin, Synthesis, 1974, 342.
6 G. A. Olah and B. G. B. Gupta, J. Org. Chem., 1983, 48, 3585; D. J.
Procter, J. Chem. Soc., Perkin Trans. 1, 2000, 1, 835.
7 Y. Shirota, T. Nagai and N. Tokura, Tetrahedron, 1969, 25, 3193; L. L.
Frye, E. L. Sullivan, K. P. Cusack and J. M. Funaro, J. Org. Chem.,
1992, 57, 697.
8 R. W. Steensma, S. Galabi, J. R. Tagat and S. W. McCombie,
Tetrahedron Lett., 2001, 42, 2281; R. P. Singh, R. M. Kamble, K. L.
Chandra, P. Sravanan and V. K. Singh, Tetrahedron, 2001, 57, 241; S.
Repichet, C. Le Roux, P. Hernandex, J. Dubac and J. R. Desmurs, J.
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10 R. J. Vaughan, US Patent, 4308215, 1981; Chem. Abstr., 1982, 96,
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11 G. A. Olah, P. S. Iyer and G. K. S. Prakash, Synthesis, 1986, 513 and
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Olah, J. Org. Chem., 1991, 56, 3192; M. Hachoumy, T. Mathew, E. C.
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Azeotropic removal of water using a Dean–Stark trap
increases the yields. As shown in Table 1, the present method
provides an easy approach to sulfones with no undesired side
products. Sulfonylation of toluene and chlorobenzene, afforded
para substituted sulfones as the major product indicating a
typical electrophilic aromatic sulfonylation. The method devel-
oped is simple, uses readily available arene- or alkanesulfonic
acids instead of sulfonyl halides, anhydrides, etc., used in
Friedel–Crafts reactions. The substitution of the typical Frie-
del–Crafts type catalyst with this resin and its convenient
regeneration bodes well for the protocol and its overall
applicability.
12 Typical sulfonylation procedure is as follows: to a solution of dry
benzenesulfonic acid (790 mg, 5.0 mmol) in dry p-xylene (40 mL),
Nafion-H (400 mg, 50 wt%) was added and stirred. The flask was fitted
with a Dean–Stark trap and the solution was refluxed continuously with
stirring for 16 hours (water formed during the reaction was removed
completely by introducing dry molecular sieves, ≈ 2.0 g, in the trap).
The reaction mixture was filtered and washed with 10% NaHCO3
solution to remove any amount of unreacted sulfonic acid. After
washing with water and drying with anhydrous Na2SO4, excess p-xylene
was distilled off and the residue was recrystallized from a mixture of
dichloromethane and n-hexane (1+2) to afford 2,5-dimethylphenyl
phenyl sulfone as a white crystalline solid, (1.0 g, 82%) mp 101–103
°C.
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