Investigation on the reduction of sulfonyl chlorides with sulfur dioxide in water as solvent

Article abstract of DOI:10.1007/s00706-013-1027-2

An operationally simple and environmentally benign method for reductive coupling of sulfonyl chlorides to the corresponding disulfides has been developed. Sulfonyl chlorides can be rapidly reduced with SO₂/KI/ H₂SO₄ system in moderate to good yields at 80 C in water. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-013-1027-2

Monatsh Chem
DOI 10.1007/s00706-013-1027-2
ORIGINAL PAPER
Investigation on the reduction of sulfonyl chlorides with sulfur
dioxide in water as solvent
Qian Zhao
•
Chao Qian Xin-zhi Chen
•
Received: 2 December 2012 / Accepted: 29 May 2013
Ó Springer-Verlag Wien 2013
Abstract An operationally simple and environmentally
benign method for reductive coupling of sulfonyl chlorides
to the corresponding disulfides has been developed. Sul-
fonyl chlorides can be rapidly reduced with SO /KI/H SO
4
as a convenient technique in organic synthesis [6]. How-
ever, the limited commercial availability of structurally
various thiols always restricted its industrial application. In
addition, thiols are very odorous compounds and their
handing needs special precaution. Since sulfonyl chlorides
are easily prepared by the reaction of chlorosulfonation,
reductive coupling of sulfonyl chlorides to the corre-
sponding disulfides is an operationally simple alternative
protocol, which also provides a procedure to synthesis of
thiols.
2
2
system in moderate to good yields at 80 °C in water.
Keywords Reduction ꢀ Catalyst ꢀ Acidity ꢀ
Sulfur dioxide ꢀ Disulfides ꢀ Sulfonyl chlorides
Introduction
Many methods concerning the synthesis of disulfides by
reductive coupling of sulfonyl chlorides have been repor-
Organic disulfides can serve as valuable intermediates in
various organic transformations especially in natural
product synthesis as well as intermediates of functional
additives and/or auxiliary agents [1–3]. They are also very
important precursors for synthesis of sulfenyl, sulfinyl,
thiols, and so on [4, 5]. Nowadays, the synthesis of organic
disulfides is attracting much attention in both academia and
industry.
ted, such as the use of sodium borohydride (NaBH ) [7],
4
lithium aluminum hydride (LiAlH ) [8], metal/acid [9],
4
hydrazine hydrate [10, 11], and so on. Nevertheless, only a
few methods are practically useful for the rapid and mild
reduction. Olah et al. [12] reported the reduction of sul-
fonyl chlorides and their derivatives with iodide in the
presence of boron halides in weakly or noncoordinating
solvents. However, long reaction time (16 h) limits its
application. More recently, low-valent oxophilic d-block
metals have become very important in deoxygenation of
different types of organic substrates. The successful utili-
zation of the lower valent complexes of Ti, Mo, and W in
effecting the deoxygenation of certain organic molecules is
the result of the usually high thermodynamic stability of
Ti-, Mo-, and W-oxo bonds [13]. Among the low-valent
oxophilic d-block metals TiCl /Al [14], MoCl /NaI [15],
The interconversion of disulfides and thiols is a funda-
mental transformation in organosulfur chemistry and such
switching plays important roles in biological systems.
Conversion of thiols to disulfides by oxidation often serves
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-013-1027-2) contains supplementary
material, which is available to authorized users.
4
5
ZrCl /NaI [16], SmI /HMPA [17], WCl /Zn, and WCl /
6
4
2
6
NaI [18] systems have been used for coupling of different
kinds of sulfonyl chlorides. Though they are very useful
reducing reagents, their application is limited. Their stor-
age is difficult because they are very sensitive to air
oxidation, which seriously restricts their application in
large scale reactions. Although a variety of reagents have
Q. Zhao ꢀ C. Qian ꢀ X. Chen (&)
Department of Chemical and Biological Engineering, Zhejiang
University, Hangzhou 310027, People’s Republic of China
e-mail: chemtec@163.com
Q. Zhao
e-mail: zhaoqian@zju.edu.cn
123

Q. Zhao et al.
been reported, a safe, simple, green, and high-yielding
procedure is still in demand.
Table 1 Optimization of the conditions in NaHSO /KI system
3
a
b
Entry
Acid/g
Time/h
Temp/°C
Yield/%
In this paper, we report a water solvent method to
complete the reduction of sulfonyl chlorides with sulfur
dioxide or sodium bisulfite in the presence of iodide in acid
media (Scheme 1), which can potentially ease cost and
simplify the procedures. The experimental parameters are
optimized for yield of the final product.
1
2
3
4
5
6
7
8
HCOOH (5)
HCOOH (10)
HCOOH (15)
HCOOH (5)
HCOOH (5)
3
80
80
93.5
93.4
93.5
93.6
93.5
93.7
93.2
85.9
3
3
80
3
90
2.5
2
100
80
H
2
SO
HCl (5)
CH COOH (5)
4
(5)
2
80
Results and discussion
3
4
80
Reaction conditions: 10 g 4-chlorobenzenesulfonyl chloride, 1 g KI,
0 g NaHSO dissolved in water added dropwise at reaction
temperature
To find the optimum reaction conditions, the reductive
coupling of 4-chlorobenzenesulfonyl chloride as a model
2
3
compound with NaHSO /KI/acid as a reducing system
3
a
Reaction time was determined by TLC
Isolated yield
under neat conditions was examined firstly. The desired
product was easily isolated by filtration. The influence of
different factors was studied, as shown in Table 1.
Different acids such as HCOOH, H SO , CH COOH,
b
Table 2 Optimization of the conditions in SO
2
/KI system
2
4
3
and HCl were tested. The reaction proceeded smoothly in
the presence of HCOOH (Table 1, entries 1–5). Increasing
the reaction temperature and the amount of acid did not
affect the yield of the final product. It should be mentioned
that HCOOH itself is capable of reduction. A similar result
was given by H SO and HCl (Table 1, entries 6–7). A
3
a
b
Entry
Acid/g
Water/cm
Time/h
Yield/%
c
d
d
d
d
1
2
3
4
5
6
H
H
H
H
H
–
2
SO
2
SO
2
SO
2
SO
2
SO
4
4
4
4
4
(5)
(5)
(5)
(5)
(5)
–
24
8
53.1
93.1
93.4
94.1
93.8
81.9
–
10
20
30
30
2
1
2
4
1
principal advantage of H SO or HCl as acid lies in that it
2
4
was the product of the chlorosulfonation reaction, which
6
provided a possibility to reuse it. With CH COOH, the
3
Reaction conditions: 10 g 4-chlorobenzenesulfonyl chloride, 1 g KI,
sulfur dioxide gas was introduced at 80 °C
reaction proceeded at a relatively slower rate, the reduction
of 4-chlorobenzenesulfonyl chloride being completed after
a
Reaction time was determined by TLC
b
4
h at 80 °C, as the yield did not exceed 90 % (Table 1,
Isolated yield
c
entry 8). It provided us the clue that relative strong acid
favors this reaction.
Sulfur dioxide gas was collected by an aqueous 30 % sodium
hydroxide solution
d
By analyzing the system, we found that NaHSO is
3
Sulfur dioxide gas was collected by a balloon
protonated by strong acids applied to form SO , so the real
2
HCl, we employed the SO /KI/H SO as reducing system;
2
2
4
attacking agent is SO . Meanwhile, more water was needed
2
the result is shown in Table 2.
to wash out the salt produced during the reaction if
Encouraged by the promising results obtained previ-
ously, the reduction of 4-chlorobenzenesulfonyl chloride in
the presence of sulfur dioxide has also been examined in
the same condition. Sulfur dioxide gas was absorbed by an
aqueous 30 % sodium hydroxide solution. Unfortunately, a
yield of less than 55 % with partial conversion during the
long reaction time was achieved (Table 2, entry 1). It
seems that sulfur dioxide gas used as a reducing agent
would disadvantageously result in a decreased reaction
rate. In order to improve the yield and reduce the reaction
time, we used a balloon to collect sulfur dioxide gas instead
NaHSO was used. According to our experimental result of
3
NaHSO , it was found that 4-chlorobenzenesulfonyl chlo-
3
ride can be easily reduced with HCOOH, HCl, or H SO to
2
4
afford the corresponding disulfides in moderate to good
yield. In an attempt to reuse the waste acid produced during
the chlorosulfonation process, we executed the reactions in
the presence of HCl or H SO . Considering the volatility of
2
4
Scheme 1
H SO
R
SO Cl
HI
2
4
2
0
of the sodium hydroxide solution. To our delight, 4,4 -
dichlorodiphenyl disulfide was obtained with a yield of
H O
2
93.1 % in 8 h (Table 2, entry 2). However, compared to
the NaHSO system, the reaction time is still too long.
3
S
R
S
I2
Finally we found that water played an important role in the
reaction. Sulfur dioxide gas and iodide solvated well when
SO2
R
1
23

Investigation on the reduction of sulfonyl chlorides
Table 3 Scope and limitations of the protocol
SO /KI/H SO
4
2
2
S
R
R-SO Cl
2
R
S
a
Entry
R
C
Time/h
Yield/%
M.p./°C
Lit. m.p./°C
1
2
3
4
5
6
7
8
6
H
5
1
93.7
94.0
94.1
94.3
93.3
83.5
91.6
92.9
3
58–60
59 [19]
4-F-C
4-Cl-C
4-Br-C
4-Me-C
3-NO -C
6
H
4
1
47.9–49
71.5–71.8
88.9–89.7
44.6–45.1
78.9–80
136.3–137.5
–
49–51 [20]
70–72 [7]
89–91 [17]
45–46 [19]
75.6–78.6 [21, 22]
137–138 [7]
–
6
H
4
1
6
H
4
1
6
H
4
1.5
2
2
6
H
4
2-Naphthyl
CH
4
3
1
Reaction conditions: 10 g substrate, 1 g KI, 5 g H
a
Isolated yield
2
SO
4
(98 wt%), 20 cm H
2
O, sulfur dioxide gas was introduced at 80 °C
3
water was added. As listed in Table 2, 20 cm water was
optimized for the yield and the minimization of the reac-
tion time (Table 2, entry 4). Increasing the amount of water
had no effect (Table 2, entry 5). Since H SO was pro-
Scheme 2
RSO Cl+10HI
S
R
+2HCl+4H2O+5I2
2
2
R
S
2
4
SO +I +2H O
H SO +2HI
2 4
2
2
2
duced during the reaction, we executed the reactions in the
absence of H SO (Table 2, entry 6). However, the result
2
4
was unsatisfactory.
The optimal condition was screened (Table 2, entry 4).
3
H SO (5 g, 98 % wt) and 20 cm H O gave a satisfactory
Conclusion
2
4
2
yield and a minimum of reaction time at 80 °C for 1 h
using water as the solvent in the 4,4 -dichlorodiphenyl
0
In conclusion, we have successfully developed a facile,
convenient, and efficient process for preparing both ali-
phatic and aromatic disulfide using sulfonyl chloride as a
starting material via use of an iodide as a catalyst in the
presence of sulfuric acid under mild reaction conditions.
Availability of the reagent, efficiency of the reactions, and
high yields of the products make this simple procedure an
attractive and a practical alternative to the known methods.
The reaction seems to offer a promising strategy for large-
scale preparations. In addition, compared to the organic
solvent, water was characterized with low toxicity, low
cost, and ready availability. The use of water as solvent is
very important for eco-friendly demand.
disulfide synthesis.
Having gained an understanding of the factors that
influence the reduction process, we explored the scope and
limitation of this method. Further reduction results are
summarized in Table 3.
As listed in Table 3, this protocol could be equally
applicable to both aliphatic and aromatic sulfonyl chlo-
rides. All reactions proceeded smoothly and quickly under
the optimal conditions. The corresponding disulfides were
isolated in good to excellent yields. It was observed that the
substituents on the arenesulfonyl chlorides and steric hin-
drance played a significant role in these reactions.
Electron-withdrawing groups on the aromatic ring induced
the reduction of arenesulfonyl chlorides more easily than
electron-donating groups. We also observed the negative
influence of steric hindrance upon the reaction times
Experimental
(
Table 3, entry 7).
All chemicals were of reagent grade and used without
further purification. All yields refer to isolated products
after purification. Products were characterized by com-
parison with authentic samples and by spectroscopy data
The reaction which takes place when reducing sulfonyl
chlorides to produce the corresponding disulfides may be
represented by the equation as shown in Scheme 2. The
1
13
function of SO in conducting the reaction is to regenerate
2
( H NMR and C NMR spectra) and melting point.
Melting points were determined using WRR melting point
the hydriodic acid by reduction of the iodine produced.
123

Q. Zhao et al.
apparatus. NMR spectra were recorded in DMSO-d or
6
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4
5
6
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0
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General procedure for the synthesis of 4,4 -
dichlorodiphenyl disulfide
1
To a mixture of 10 g 4-chlorobenzenesulfonyl chloride
3
0.047 mol) in 20 cm water was added 5 g sulfuric acid
98 wt%) and 1 g KI. The mixture turned purple when
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(
4
3. Walton RA (1972) Prog Inorg Chem 16:1
6:2408
(
1
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1
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filtration.
1
1
2
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Acknowledgments The authors gratefully acknowledge the funding
support by a grant from the National Natural Science Foundation of
China (No. 21076183), and the Science and Technology Innovation
Team of Zhejiang Province (No. 2009R50002).
2
2
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23