Direct sulfonylation of aromatic rings with aryl or alkyl sulfonic acid using supported P2O5/Al2O3

Article abstract of DOI:10.1080/104265090902796

Direct sulfonylation of aromatic rings with aryl or alkyl sulfonic acid supported P₂O₅/Al₂O₃ (w/w 50%) under heterogeneous conditions in short reaction time and high yields. Copyright Taylor & Francis Inc.

Full text of DOI:10.1080/104265090902796

This article was downloaded by: [University of South Florida]
On: 09 October 2014, At: 13:09
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Direct Sulfonylation of
Aromatic Rings with Aryl
or Alkyl Sulfonic Acid Using
Supported P2O5/Al2O3
Abdol. R. Hajipour a , Amin Zarei a , Leila Khazdooz
a , Seied A. Pourmousavi a , Bi Bi F. Mirjalili b & A. E.
Ruoho c
a Pharmaceutical Research Laboratory, College
of Chemistry, Isfahan University of Technology ,
Isfahan, Iran
b Department of Chemistry , College of Science,
Yazd University , Yazd, Iran
c Department of Pharmacology , University of
Wisconsin Medical School , Madison, Wisconsin, USA
Published online: 19 Aug 2006.
To cite this article: Abdol. R. Hajipour , Amin Zarei , Leila Khazdooz , Seied
A. Pourmousavi , Bi Bi F. Mirjalili & A. E. Ruoho (2005) Direct Sulfonylation of
Aromatic Rings with Aryl or Alkyl Sulfonic Acid Using Supported P2O5/Al2O3 ,
Phosphorus, Sulfur, and Silicon and the Related Elements, 180:9, 2029-2034, DOI:
10.1080/104265090902796
To link to this article: http://dx.doi.org/10.1080/104265090902796
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no

representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 180:2029–2034, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090902796
Direct Sulfonylation of Aromatic Rings with Aryl or Alkyl
Sulfonic Acid Using Supported P2O5/Al2O3
Abdol. R. Hajipour
Amin Zarei
Leila Khazdooz
Seied A. Pourmousavi
Pharmaceutical Research Laboratory, College of Chemistry, Isfahan
University of Technology, Isfahan, Iran
Bi Bi F. Mirjalili
Department of Chemistry, College of Science, Yazd University, Yazd,
Iran
A. E. Ruoho
Department of Pharmacology, University of Wisconsin Medical School,
Madison, Wisconsin, USA
Direct sulfonylation of aromatic rings with aryl or alkyl sulfonic acid supported
P2O5/Al2O3 (w/w 50%) under heterogeneous conditions in short reaction time and
high yields.
Keywords Diphosphorus pentoxide; sulfonylation; sulfones
INTRODUCTION
Aryl sulfones are useful compounds in organic synthesis and industry.1,2
Diaryl sulfones are important biological molecules against leishma-
niasis, malaria, infections in patients with AIDS, and discoid lupus
erythematosus.3,4 Diaryl or aryl/alkyl sulfones can be synthesized by
Received July 26, 2004; accepted October 5, 2004.
We gratefully acknowledge the funding support received for this project from the
Isfahan University of Technology (IUT), IR Iran (A. R. H.), and the financial support
made by the research affairs, Yazd University, Yazd, Iran. Further financial support from
the Center of Excellency in Chemistry Research (IUT) is gratefully acknowledged.
Address correspondence to Abdol. R. Hajipour, University of Wisconsin Medical
School, Department of Pharmacology, 1300 University Avenue, Madison, WI, USA.
E-mail: arhajipour@facstaff.wisc.edu
2029

2030
A. R. Hajipour et al.
Friedel-Crafts sulfonylation of aromatic compounds5−10 or by direct sul-
fonylation of arenes by sulfonic acids by using Nafion-H,11 polyphosh-
phoric acids,12 or phospours pentoxide/methansulfonic acid.13,14 Unfor-
tunately most of these methods suffer at least from one of the following
disadvantages: (1) high cost of preparations, (2) long reaction time, (3)
hygroscopisity, (4) high acidity, (5) instability, and (6) tedious work-up
procedures. Using P2O5:MeSO3H has certain unfortunate such as time
consuming, didtllation of methansufonic acid before using thermal de-
composition of a reagent and using 10 fold of methansulfonic acid.
RESULTS AND DISCUSSION
Over the last two decades, the use of solid supports has become popular
due to their characteristic properties such as enhanced selectivity and
reactivity, a straightforward work-up procedure, milder reaction condi-
tions, and associated ease of manipulation.15,16 Because of our interest
in the development of using solid support in organic chemistry,17 we
wish to report an efficient procedure for the preparation of aromatic
sulfones from aryl or alkyl sulfonic acid with P2O5/Al2O3 under hetero-
geneous conditions. Based on the ability of P2O5, and in order to de-
16
crease air sensitivity of it, we supported P2O5 on Al2O3 and used for
synthesis of sulfones via direct sulfonylation of aromatic rings. Prepa-
ration of symmetric and unsymmetric aromatic sulfones was achieved
in moderate to good yields (55–90%) via a Friedel-Crafts type of sul-
fonylation of arenes with various sulfonic acids (Scheme 1).
P2O5/Al2O3 (w/w 50%)
R1 − SO3H + Ar − H −−−−−−−−−−−−−→ R1SO2Ar
reflux
R1 = alkyl or aryl
SCHEME 1
The sulfonylation reactions were carried out by refluxing a stirring mix-
ture of the corresponding aryl or alkyl sulfonic acid in excess of the aro-
matic compounds in the presence of supported P2O5/Al2O3 (w/w 50%)
(Table I). The starting aromating compounds act either as a substrate
or a solvent. The present method provides an efficient, clean, and fast
approach for the preparation of sulfones without any by-product. We
found that the optimized reaction time for all of the reaction was 1 h
under refluxing conditions.
In order to evaluate the synergy between P2O5 and Al2O3, we per-
formed several experiments. When we examined the reaction of 5 mL of

Direct Sulfonylation of Aromatic Rings
2031
TABLE I Sulfonylation of Aromatic Rings by Aryl or Alkyl Sulfonic
Acid in the Presence of Supported P2O5/Al2O3 (w/w 50%).
Sulfonic
acid
Aromatic
compound
Yield (%)b Yield Melting
(O:P)
Entry
Producta
(%)c point (◦C)
25 125–127
32 147–150d
1
2
Benzene
Toluene
55
75
(10:90)
3
4
5
O-xylene
M-xylene
P-xylene
80
82
85
35 118–120
38
58–60
35 105–107
6
7
Anisole
90
(15:85)
44
79–81d
Mesitylene
80
70
30 115–117
32 100–104
8
9
Cumene
Bromobenzene
60
(10:90)
0
125–128d
25 117–118
35
83–85d
10
11
Benzene
Toluene
56
82
(20:80)
12
13
O-xylene
M-xylene
70
72
34 111–114
37
88–90
14
P-xylene
75
35 104–106
15
16
Anisole
87
(40:60)
47
32
80–82d
79–81
Mesitylene
85
(Continued on next page)

2032
A. R. Hajipour et al.
TABLE I Sulfonylation of Aromatic Rings by Aryl or Alkyl Sulfonic
Acid in Presence of Supported P2O5/Al2O3 (w/w 50%) (Continued)
Sulfonic
acid
Aromatic
compound
Yield (%)b Yield Melting
(O:P)
Entry
17
Producta
(%)c point (◦C)
Cumene
80
30
0
96–97
18
Bromobenzene
65
85–87d
(15:85)
19
CH3 SO3H P-xylene
60
—
136–138
20
21
Anisole
65
(18:82)
—
—
110–112d
126–128
Mesitylene
55
aAll the products were characterized by 1H-NMR, FT-IR, TLC and physical data with
authentic samples.9
bIn excess of substrate in 1 h.
cIn 1,2-dicholoroethane in 2 h.
dMelting point of mixture product.9
anisole and one molar ratio of p-toluenesulfonic acid with P2O5 without
using any Al2O3, the yield was only 60% after 10 h of refluxing. We also
treated 1 mmol of anisole with 1 mmol of p-toluenesulfonic acid with
the supported P2O5 on Al2O3 (0.34 g) in ClCH2CH2Cl under refluxing
conditions. The yield was 50% after 10 h of refluxing, as is shown in
Table I. The yield of the reaction 1,2-dicholoroethane is lower and the
reaction time is longer. Therefore, we decided to perform the reaction of
sulfonic acid derivatives in excess aromatic compounds with supported
P2O5 on Al2O3.
In summary, the advantage of this methodology over the reported
methods is the availability of the starting materials, simplicity of sul-
fonylation procedure, a clean work-up, a short reaction time, high yields,
and an easily handled and inexpensive reagent.
EXPERIMENTAL SECTION
All yields refer to isolated products. The products were characterized
1
by comparison with authentic samples (IR, H-NMR spectra, melting
1
and boiling points, and TLC). All H-NMR spectra were recorded at
300 MHz in CDCl3 and CCl4 relative to TMS (0.00 ppm).

Direct Sulfonylation of Aromatic Rings
2033
Preparation of P2O5/Al2O3 (w/w 50%)
We placed Al2O3 (active acidic-0.063–0.200 mm) in an oven at 120◦C for
24 h and then P2O5 (5 g, weighed out in a drybox) was added on Al2O3
(5 g), mixed, and then placed in a stoppered flask for use.
Preparation of Mesityl Tolyl Sulfone
Typical Procedure
To a mixture of p-toluene-sulfonic acid monohydrate (0.38 g, 2 mmol)
and dry mesitylene (5 mL) was added to P2O5/Al2O3 (w/w 50%, 0.67 g).
The solution was refluxed continuously with stirring for 1 h. The re-
action mixture was filtered and washed with 10% NaHCO3 solution to
remove the unreacted sulfonic acid. After washing with water and dry-
ing with anhydrous Na2SO4, excess mesitylene was distilled off by a
vacuum and the residue was recrystalized from cyclohexane to afford
mesityl tolyl sulfone as a white crystalline solid (0.44 g, 80%), mp.: 115–
117◦C (reported: 115–117◦C),6 1H NMR δ (90 MHz, CDCl3) 7.66 (d, 2H),
7.33 (d, 2H), 6.96 (S, 2H), 2.62 (S, 6 H), 2.42 (S, 3H), 2.32 (S, 3H), IR
(KBr) cm−1: 1140 (S, SO2), 1310 (S, SO2).
REFERENCES
[1] (a) F. R. Jensen and G. Goldman, In Friedel-Crafts and Related Reaction; G. Olah,
Ed.; New York: Wiley Intrscience (1964); Vol. 3, pp. 1319–1367; (b) N. S. Simpkins
Sulfones in Organic Synthesis; Oxford: Pergamon Press (1993).
[2] K. M. Roy, In Ullmann’s Encyclopedia of Industrial Chemistry; W. Gerhartz, Ed.;
Weinheim: VCH (1985); Vol. A 25, pp. 487–501.
[3] R. C. Hastings and S. G. Franzblau, Ann. Rev. Pharmacol. Toxicol., 28, 231 (1966).
[4] G. Wozel, Int. J. Dermatol., 28, 17 (1989).
[5] S. Repichet, C. L. Roux, and J. Dubac, Tetrahedron Lett., 40, 9233 (1999).
[6] A. R. Hajipour, S. E. Mallakpour, and Gh. Imanzadeh, Indian J. Chem., 40B, 237
(2001).
[7] P. Laidlaw, D. Bethell, S. M. Brown, G. Watson, D. J. Willock, and G. J. Hutchings,
J. Molecular Catalysis, 178, 205 (2002).
[8] B. M. Choudary, N. S. Chowdari, M. L. Kantam, and R. Kannan, Tetrahedron Lett.,
40, 2859 (1999).
[9] C. G. Frost, J. P. Hartley, and D. Griffin, Tetrahedron Lett., 43, 4789 (2002).
[10] R. P. Singh, R. M. Kamble, K. L. Chandra, P. Saravanane, and V. K. Singh, Tetra-
hedron, 57, 241 (2001).
[11] G. A. Olah, T. Mathew, and G. K. S. Parakash, Chem. Commun., 1969 (2001).
[12] H. J. Sipe, D. W. Clary, and S. B. White, Synthesis, 283 (1984).
[13] M. Ufda, K. Uchiyama, and T. Kano, Synthesis, 323 (1984).
[14] P. E. Eaton, G. R. Caqrlson, and J. T. Lee, J. Org. Chem., 38, 4071 (1978).
[15] K. Smith, Ed., Solid Supports and Catalysts in Organic Synthesis, New York:
Prentice Hall (1992).

2034
A. R. Hajipour et al.
[16] J. H. Clark, Catalysis of Organic Supported Inorganic Reagents, NewYork: VCH,
(1994), p. 38.
[17] (a) A. R. Hajipour, S. E. Mallakpour, and H. Adibi, Indian J. Chem., 41B, 2425 (2002);
(b) A. R. Hajipour, S. E. Mallakpour, and Gh. Imanzadeh, Chem. Lett., 99 (1999); (c)
A. R. Hajipour, S. E. Mallakpour, and H. Adibi, Sulfur Lett., 25, 155 (2002); (d) A. R.
Hajipour, S. E. Mallakpour, I. Mohammadpoor-Baltork, and H. Backnezhad, Synth.
Commun., 32, 771 (2002); (e) A. R. Hajipour, S. E. Mallakpour, and H. Adibi, J. Org.
Chem., 67, 8666 (2002).