Simple method for the preparation of symmetrical alkyl and aryl disulfides with alkyl sulfonyl halides in nitrogenous base

Article abstract of DOI:10.1080/00397910701459498

In the present study, the reaction of thiols with alkyl sulfonyl halides was carried out in a nitrogenous base to compare the reactivity of -SH with that of -OH, which, however, led to the formation of disulfides. The reaction achieved as a result offers the use of an inexpensive reagent, quantitative yields of the product, and simplicity for the formation of the S-S bond. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701459498

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Simple Method for the Preparation of
Symmetrical Alkyl and Aryl Disulfides with
Alkyl Sulfonyl Halides in Nitrogenous Base
Firdous Imran Ali a , Imran Ali Hashmi a , Bina S. Siddiqui b & Munawwer
Rasheed a
a Department of Chemistry , University of Karachi , Karachi, Pakistan
b H.E.J. Research Institute of Chemistry, University of Karachi, International
Center for Chemical Sciences , Karachi, Pakistan
Published online: 09 Aug 2007.
To cite this article: Firdous Imran Ali , Imran Ali Hashmi , Bina S. Siddiqui & Munawwer Rasheed (2007)
Simple Method for the Preparation of Symmetrical Alkyl and Aryl Disulfides with Alkyl Sulfonyl Halides in
Nitrogenous Base, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 37:15, 2461-2465, DOI: 10.1080/00397910701459498
To link to this article: http://dx.doi.org/10.1080/00397910701459498
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Synthetic Communicationsw, 37: 2461–2465, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701459498
Simple Method for the Preparation of
Symmetrical Alkyl and Aryl Disulfides with
Alkyl Sulfonyl Halides in Nitrogenous Base
Firdous Imran Ali and Imran Ali Hashmi
Department of Chemistry, University of Karachi, Karachi, Pakistan
Bina S. Siddiqui
H.E.J. Research Institute of Chemistry, University of Karachi,
International Center for Chemical Sciences, Karachi, Pakistan
Munawwer Rasheed
Department of Chemistry, University of Karachi, Karachi, Pakistan
Abstract: In the present study, the reaction of thiols with alkyl sulfonyl halides was
carried out in a nitrogenous base to compare the reactivity of -SH with that of -OH,
which, however, led to the formation of disulfides. The reaction achieved as a
result offers the use of an inexpensive reagent, quantitative yields of the product,
and simplicity for the formation of the S-S bond.
Keywords: disulfides, methanesulfonyl chloride, pyridine, thiols
INTRODUCTION
Diaryl and dialkyl disulfides have achieved much attention because of their
application in many important synthetic reactions, for instance, synthesis of
nucleotide derivatives,[1] addition of substituted alkenes to vinylcyclopro-
pane,[2] conversion of hydroxy acids into lactones,[3] and several other
syntheses.[4–7] Disulfides play a vital role in living systems.[8,9] In the
Received December 11, 2006
Address correspondence to Firdous Imran Ali, Department of Chemistry, Univer-
sity of Karachi, Karachi, Pakistan. E-mail: firdousilyas@yahoo.com
2461

2462
F. I. Ali et al.
present article, we are reporting disulfide formation from thiols on their
reaction with methanesulfonyl chloride in pyridine at 08C, in almost theore-
tical yield. The present reaction offers the use of an inexpensive reagent,
quantitative yields of the product, and simplicity. The scope of the reagent
can be measured from the wide range of substrates entered in Table 1. In all
cases, mild conditions have been used.
A great deal of synthetic work has already been carried out for the
formation of disulfides from thiols[10–18] and other reagents.[19–21] In 1988,
Langler et al. reported the formation of disulfides with methanesulfonyl
chloride in the presence of 2,4,6-tribromophenol as catalyst using NaH as
base. The reaction is suggested to proceed via 2,4,6-tribromosulfonate
formation followed by the attack of mecaptide ion.[22] Our procedure uses
the reduction of acyl ammonium salt (mesyl pyridinium chloride) with mer-
captide anions (Scheme 1) in analogy with the formation of acyl
ammonium salt reported earlier.[23] The formation of the mesyl pyridinium
Table 1. Synthesis of symmetrical aryl and alkyl disulfides with mesyl chloride in
pyridine
Yield
(%)
Time
(min)
Entry
1
Substrate
Product
100
15
2
3
95
65
20
15
4
5
6
7
8
C2H5SH
(C2H5S)2
78
70
76
91
89
25
30
25
30
25
n-C3H7SH
iso-C3H7SH
n-C4H9SH
n-C6H13SH
(n-C3H7S)2
(iso-C3H7S)2
(n-C4H9S)2
(n-C6H13S)2

Preparation of Symmetrical Alkyl and Aryl Disulfides
2463
1
chloride was supported by H NMR spectroscopic studies. Methanesulfonyl
1
chloride was added to a cold solution (08C) of C5D5N, and its H NMR
spectra were recorded five times, each with an interval of 2 min for 10 min.
Each time, the signal of -SO2CH3 was observed at the same chemical shift,
that is, d 4.39 as against -SO2CH3 of MsCl alone at d 3.7;[24] in CD3OD, it
appeared at d 3.03, which shifted to d 3.88 after the addition of tributyl amine.
The formation of disulfides proceeded well with nitrogenous bases,
whereas in the case of nonnitrogenous base, the thiophenol was recovered
as such (Table 2).
Reaction with different alkyl sulfonyl and aryl sulfonyl halides showed
that other alkyl sulfonyl halides react in the same way as mesyl chloride,
whereas with aryl halides the desired results were not achieved and the
starting material was recovered unchanged (Table 3).
The general applicability of the reaction was observed on elaborating the
reaction to various thiols and thiophenols (entries 2–8, Table 1). In each case,
a solution of thiol or thiophenol (1 mmol) in anhydrous pyridine (1.2 mmol)
Scheme 1. Proposed mechanism of disulfide formation.

2464
F. I. Ali et al.
Table 2. Effect of bases on phenyl disulfide formation
Substrate
Base
Temp. (8C) Time
Yield (%)
1
2
3
4
5
6
Pyridine
Lutidine
Diisopropyl amine
0
0
15 min
5 min
20 min
25 min
72 h
100
100
98
10
0
rta
0–rt
Tributyl amine
Trimethyl amine (acetonitrile)
Potassium t-butoxide (n-BuOH)
100
95
72 h
0
art ¼ Room temperature.
was treated with methanesulfonyl chloride (1.2 mmol) at 08C. The reaction
time required for completion of the reaction was monitored through thin-
layer chromatography (TLC) and found variable. All products were identified
by comparing their physical and spectroscopic data with those published in
literature.[4,5]
The phenols were also treated with the same reagent under the same con-
ditions, but their dimers were not obtained as observed in the case of thiols.
EXPERIMENTAL
General
All chemicals were purchased from Aldrich. TLC was carried out on
1
homemade silica-gel (GF254) plates; H NMR were recorded in CDCl3 on a
Bruker Aspect 3000 AM 300 spectrophotometer, Bruker Aspect 4000 AM
400, and AMX 500 spectrophotometer, operating at 300, 400, and 500
MHz, respectively.
Representative Procedure for Disulfide Formation of Thiophenol
A solution of the thiophenol (1) (100 mg, 0.219 mmol) in anhydrous pyridine
(2 ml, 0.3 mmol) was treated with methanesulfonyl chloride (0.041 ml,
Table 3. Effect of different sulfonyl halides on phenyl disulfide formation
Substrate
Sulfonyl halide
Temp. (8C) Time
Yield (%)
1
2
3
4
Methanesulfonyl chloride
Ethanesulfonyl chloride
Toluenesulfonyl chloride
1-Naphthylsulfonyl chloride
0
0
15 min
10 min
72 h
100
100
0
rt
rt
72 h
0

Preparation of Symmetrical Alkyl and Aryl Disulfides
2465
0.54 mmol) at 08C, and the reaction was monitored by TLC. After 10 min, 1
was almost completely consumed, and white precipitates were obtained. The
reaction product was poured into ice-cold water, and the crystals of diphenyl
disulfide obtained were filtered, washed several times with ice-cold water, and
air dried. Other products (entries 2–8) were obtained upon usual workup. (The
reaction mixture was partitioned between water and ethyl acetate; the ethyl
acetate phase was washed, dried, and evaporated under reduced pressure.)
REFERENCES
1. Mukaiyama, T.; Hashimoto, M. J. Am. Chem. Soc. 1972, 8528–8532.
2. Feldman, K. S.; Romanelli, A. L.; Rukle, R. E., Jr.; Miller, R. F. J. Am. Chem. Soc.
1988, 3300–3302.
3. Corey, E. J.; Brunelle, D. J. Tetrahedron Lett. 1976, 3409–3442.
4. Hiroi, K.; Rotsuji, K.; Sato, S. Chem. Lett. 1981, 559.
5. Nakagawa, I.; Hata, T. Tetrahedron Lett. 1975, 1409–1412.
6. Russell, G. A.; Kulkarni, S. V. J. Org. Chem. 1993, 58, 2678–2685.
7. Mukiyama, T.; Goto, K.; Matsuda, R.; Ueki, M. Tetrahedron Lett. 1970,
5293–5296.
8. Greene, A. E.; Padilla, A.; Crabbe, P. J. Org. Chem. 1978, 43, 4377–4379.
9. Miyake, H.; Iguchi, S.; Itoh, H.; Hayashi, M. J. Am. Chem. Soc. 1977, 99,
3536–3537.
10. Tes-Lock, H.; Hall, T. W.; Wong, C. M. Synthesis 1974, 872–873.
11. Firouzabadi, H.; Mohajer, D.; Entezari-Moghadam, M. Bull. Chem. Soc. Jpn.
1988, 61, 2185–2189.
12. Iranpoor, N.; Zeynizadeh, B. Synthesis 1999, 1, 49–50.
13. Demir, A. S.; Igdir, A. C.; Mahasneh, A. S. Tetrahedron. Lett. 1999,
12399–12404.
14. Hart, T. W.; Vine, M. B.; Walden, R. N. Tetrahedron Lett. 1985, 26, 3879–3882.
15. Nakagawa, K.; Shiba, S.; Horikawa, M.; Sato, K.; Nakamura, H.; Harada, N.;
Harada, F. Synth. Commun. 1980, 10, 305–309.
16. Kato, E.; Oya, M.; Iso, T.; Iwao, J. I. Chem. Pharm. Bull. 1986, 34, 486–495.
17. Ley, S. V.; Meerholz, C. A.; Barton, D. H. R. Tetrahedron 1981, 17, 213–223.
18. Xiaoming, W.; Rieke, R. D. Synth. Commun. 1996, 26, 191–196.
19. Firouzabadi, H.; Karimi, B. Synthesis 1998, 500–502.
20. Decker, Q. W.; Post, H. W. Synthesis 1957, 145–146.
21. Hansen, H. C.; Senning, A.; Hazell, R. G. Tetrahedron 1985, 41, 5145–5158.
22. Durkin, K. A.; Langler, R. F.; Morrison, N. A. Can. J. Chem. 1988, 66,
3070–3076.
23. Optz, G. Angew. Chemie 1967, 6, 107–194 (and references cited therein).
24. Aldrich Library of NMR Spectra.