Synthesis of diaryl disulfides via the reductive coupling of arylsulfonyl chlorides

Article abstract of DOI:10.1016/j.tetlet.2009.10.061

A facile synthesis of diaryl disulfides from arylsulfonyl chlorides in the presence of triphenylphosphine has been developed.

Full text of DOI:10.1016/j.tetlet.2009.10.061

Tetrahedron Letters 50 (2009) 7340–7342
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of diaryl disulfides via the reductive coupling of arylsulfonyl chlorides
*
George W. Kabalka , Marepally Srinivasa Reddy, Min-Liang Yao
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, TN 37996-1600, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile synthesis of diaryl disulfides from arylsulfonyl chlorides in the presence of triphenylphosphine
Received 21 May 2009
Revised 9 October 2009
Accepted 13 October 2009
Available online 30 October 2009
has been developed.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Arylsulfonyl chloride
Triphenylphosphine
Disulfide
Coupling
Diaryl disulfides are valuable intermediates1 in the synthesis of
natural products and medicinal compounds.2 They are also impor-
tant starting materials in the preparation of sulfenyl3 and sulfinyl4
reagents. Diaryl disulfides are generally synthesized from aryl thi-
ols,5 aryl sulfonyl esters,6 aryl sulfonic acids,6 and their correspond-
ing salts.7 In the last decade, the preparation of diaryl disulfides
using sulfonyl chlorides has been of interest because of their ready
availability.8 Each of the reagents such as silphos [PCl3Àn(SiO2)n]/
molecular iodine,9 samarium in DMF,10 SmI2/HMPA,11 piperidinium
tetrathiotungstate,12 HI/glacial acetic acid,13 Mo(CO)6 in tetrameth-
ylurea,14 WCl6/NaI or WCl6/Zn,15 BI3 or BBr3/KI,16 iodotrimethylsi-
lane,17 tri-n-propylamine/trichlorosilane,18 aluminum iodide
(AlI3),19 and diphosphorus tetraiodide (P2I4)7 has been used to re-
duce sulfonyl halides to the corresponding disulfides. Previously,
we20 demonstrated that the reduction of alkyl or aryl sulfonic acid
derivatives and sulfoxides to the corresponding disulfides could be
achieved by using a boron triiodide-N,N-diethylaniline system. Fuji-
mori et al.21 reported that the aryl sulfonic acids, their salts, and alkyl
sulfonates can be reduced to the corresponding aryl thiols quantita-
tively using triphenylphosphine in the presence of iodine. We now
wish to report that triphenylphosphine itself is an efficient reagent
for the conversionof arylsulfonyl chloridesto the corresponding dia-
ryl disulfides under mild reaction conditions (Scheme 1).
were carried out in THF at room temperature; approximately 50%
of the sulfonyl chloride was consumed within 30 min to give disul-
fide in 42% yield. Lengthening the reaction time to 24 h did not af-
fect the yield of the reaction. When the ratio of triphenylphosphine
to para-toluenesulfonyl chloride increased to 2:1, under the same
reaction conditions, the disulfide product was isolated in 92% yield
within 30 min. The need for 1 equiv of triphenylphoshine for each
oxygen in the sulfonyl chloride reagents is not surprising based on
earlier studies involving the reduction of arylsulfonyl iodides (pro-
posed intermediates generated in situ from aryl sulfonic acids and
I2) using triphenylphospine.6 Dichloromethane and benzene were
also evaluated as reaction solvents and the yields were 80% and
72%, respectively. However, tetrahydrofuran was the most effec-
tive solvent. The reaction was found to be sensitive to water and
a trace amount of aryl thiol was detected in its presence, which re-
sulted in decreased isolated yield of the desired disulfide. When
the reactions were carried out in the presence of 0.5 equiv of water,
a 1:1 mixture of thiol and disulfide formed in 80% yield. Using
aqueous THF: (v:v = 1:1) inhibited the reaction completely.
Various arylsulfonyl chlorides were then evaluated.23 As the
data in Table 1 reveal, reaction yields were not affected by the elec-
tronic nature of the substituents present on the aryl rings. How-
ever, reactions of arylsulfonyl chlorides bearing a nitro group
para-Toluenesulfonyl chloride22 was chosen as the model sys-
tem for the initial investigation. Preliminary experiments were car-
ried out using varying ratios of triphenylphosphine and para-
toluenesulfonyl chloride. Initially a 1:1 ratio of para-toluenesulfo-
nyl chloride and triphenylphosphine was used and the reactions
Z
Z
Z
Ph P
3
SO Cl
S S
+
Ph PO
3
2
THF, rt
Z = Me, OMe, Br, CN, NO etc
2
* Corresponding author. Tel.: +1 865 974 3260.
E-mail address: kabalka@utk.edu (G.W. Kabalka).
Scheme 1. Reductive coupling of arylsulfonyl chloride using triphenylphosphine.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.061

G. W. Kabalka et al. / Tetrahedron Letters 50 (2009) 7340–7342
7341
Table 1
SO Cl
SO Cl
2
2
Reduction of arylsulfonyl chlorides to disulfides using triphenylphosphinea
1a + 1b +
Ph P
3
+
Me
S
S
Br
THF, rt
2.0 equiv. PPh
3
Ar-S-S-Ar
Ar-SO Cl
2
2
anhydrous THF/ rt
Me
Br
1
Scheme 2. Cross-coupling reaction of the sulfonyl chlorides.
Entry
1
Ar
Yieldb (%)
92
Me
Br
At present, the reaction mechanism is not well defined. The iso-
lation of Ph3PO indicates that the reaction proceeds through an
ArSCl intermediate since Ph3P is capable of extracting oxygen from
a variety of substrates6,25 including aryl sulfonyl iodides to form
the corresponding deoxygenated derivatives.6 In addition, the
spontaneous decomposition of MeSCl to MeSSMe is also known
in the literature.26 The detection of the cross-coupling product 4-
bromophenyl 4-methylphenyl disulfide (2) by GC–MS from a reac-
tion using an equimolar mixture of para-toluenesulfonyl chloride
and para-bromosulfonyl chloride suggests the possibility of radical
intermediates in the process although an ionic process cannot be
ruled out at this time.19,27 (Scheme 2).
1a
1b
2
3
92
91
1c
4c
75
85
O2N
1d
In conclusion, a practical method for the synthesis of diaryl
disulfides using commercially available and inexpensive triphenyl-
phosphine and arylsulfonyl chlorides in anhydrous tetrahydrofu-
ran under mild reaction conditions has been developed.
5c
1e
NO2
Acknowledgments
1f
6
7
8
95
80
90
S
Financial support from U.S. Department of Energy, and the Rob-
ert H. Cole Foundation is acknowledged.
1j
References and notes
NC
1k
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Me
Me
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Dougherty, G.; Haas, O. J. Am. Chem. Soc. 1937, 59, 2469.
3. Kuhle, E. The Chemistry of the Sulfenic Acids; Georg Thieme: Stuttgart, 1973.
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9
80
1l
F
10
11c
12
91
85
92
1m
1n
O N
2
MeO
1o
a
Reactions were carried out on a 1.0 mmol scale in dry THF (5 mL) at room
temperature unless noted otherwise.
All products gave satisfactory 1H NMR and 13C NMR spectra.
b
14. Alper, H. Angew. Chem., Int. Ed. Engl. 1969, 81, 706.
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c
Reactions were carried out at 0 °C.
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22. To remove a trace amount of sulfonic acid, para-toluenesulfonyl chloride was
recrystalized from hexanes prior to use.
(entries 4, 5, and 11) generated complex mixtures at room temper-
ature due to a known side reaction between the nitro group and
triphenylphosphine,24 but this side reaction could be eliminated
if the reactions were carried out at 0 °C. In addition, in some cases,
small amounts of aryl thiols were detected due to the presence of
trace amounts of sulfonic acids in the starting sulfonyl chlorides.
The formation of aryl thiols could be totally eliminated by purify-
ing the arylsulfonyl chlorides (recrystallization) prior to use.
23. Typical reaction procedure: To
a solution of para-toluenesulfonyl chloride
(190 mg, 1.0 mmol) in tetrahydrofuran (5 mL) was added triphenylphosphine
(524 mg, 2.0 mmol). The mixture was stirred at room temperature and

7342
G. W. Kabalka et al. / Tetrahedron Letters 50 (2009) 7340–7342
monitored by TLC. After completion of the reaction, the solvent was removed
25. (a) Wittig, G.; Schöllkopf, U. Chem. Ber. 1954, 87, 1318; (b) Mitsunobu, O.;
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27. The light yellow color of the reaction mixtures suggests that chlorine may be a
byproduct. However, attempts to detect chlorine using wet KI-Starch paper
were unsuccessful.
under reduced pressure and the residue was dissolved in a minimum amount
of ethyl acetate (4 mL). To this solution, hexane was added dropwise (about
30 mL) and the byproduct triphenylphosphine oxide was precipitated and was
removed by filtration. Concentration of the filtrate under reduced pressure and
silica gel column chromatography using hexane as eluant yielded the desired
product (114 mg, 92% yield).
24. Masaki, M.; Fukui, K.; Kita, J. Bull. Chem. Soc. Jpn. 1977, 50, 2013.