An approach to disulfide synthesis promoted by sulfonyl chloride in sodium bicarbonate aqueous media

Article abstract of DOI:10.1080/10426500802529051

A mild and efficient protocol for the synthesis of disulfides in aqueous media using mercaptans promoted by sulfonyl chloride is reported. This reaction offers the advantages of mild reaction conditions, short reaction time, high yields, and simple operation. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500802529051

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Phosphorus, Sulfur, and Silicon
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An Approach to Disulfide
Synthesis Promoted by Sulfonyl
Chloride in Sodium Bicarbonate
Aqueous Media
Huilong Xiao a , Jiuxi Chen a , Miaochang Liu a ,
Huayue Wu a & Jinchang Ding a
a College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou, PR China
Published online: 21 Sep 2009.
To cite this article: Huilong Xiao , Jiuxi Chen , Miaochang Liu , Huayue Wu & Jinchang
Ding (2009) An Approach to Disulfide Synthesis Promoted by Sulfonyl Chloride in
Sodium Bicarbonate Aqueous Media, Phosphorus, Sulfur, and Silicon and the Related
Elements, 184:10, 2553-2559, DOI: 10.1080/10426500802529051
To link to this article: http://dx.doi.org/10.1080/10426500802529051
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Phosphorus, Sulfur, and Silicon, 184:2553–2559, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802529051
An Approach to Disulfide Synthesis Promoted by
Sulfonyl Chloride in Sodium Bicarbonate Aqueous Media
Huilong Xiao, Jiuxi Chen, Miaochang Liu, Huayue Wu,
and Jinchang Ding
College of Chemistry and Materials Engineering, Wenzhou University,
Wenzhou, PR China
A mild and efficient protocol for the synthesis of disulfides in aqueous media using
mercaptans promoted by sulfonyl chloride is reported. This reaction offers the ad-
vantages of mild reaction conditions, short reaction time, high yields, and simple
operation.
Keywords Aqueous media; disulfides; sulfonyl chloride
INTRODUCTION
The disulfide moiety exists in proteins and various natural products as
well as pharmacologically active compounds.1 For example, the synthe-
sis of nucleotide derivatives,2 addition reactions,3 exchange reactions,4
insert reactions,5 and other applications6 all exhibit chemistry asso-
ciated with this group. Furthermore, polysulfide bonds have a well-
known utility in the synthesis of polymers, such as rubber, and com-
pounds that involve the disulfide moiety, which have been proved to be
useful in the design of rechargeable lithium batteries.7
General methods for the synthesis of disulfides involve oxida-
tion of mercaptans by various oxidants such as molecular oxy-
gen,8a metal ions,8b Bu3SnOMe/FeCl3,8c nitric oxide,8d halogens,8e–8h
sodium perborate,8i borohydride exchange resin (BER)-transition
metal salt system,8j morpholine iodine complex,8k PCC,8l ammonium
persulfate,8m KMnO4/CuSO4,8n H2O2,8o solvent-free permanganate,8p
PVP-N2O4,8q and cesium fluoride-Celite,8r 2,6-dicarboxypyridinium
Received 8 July 2008; accepted 6 October 2008.
We are grateful to the Natural Science Foundation of Zhejiang Province (Y4080107)
and Technology Program of Zhejiang Province (No. 2003C31026, 2005C31036) for finan-
cial support.
Address correspondence to Huayue Wu, College of Chemistry and Materials Engi-
neering, Wenzhou University, Wenzhou 325027, PR China. E-mail: hywu3@163.com
2553

2554
H. Xiao et al.
chlorochromate,8s and NH4OH.8t Although a variety of catalytic sys-
tems have been explored for the synthesis of disulfides, some meth-
ods suffer from one or more disadvantages such as long reaction
time, inefficient catalyst,8b–c9 low yield, toxic solvent,10 excess sub-
strates or catalysts, and harsh reaction conditions. Moreover, in some
cases they suffer from over-oxidation of the final product.11 There-
fore, the development of facile and environmental friendly meth-
ods for the synthesis of disulfides is essential for organic synthe-
sis. In continuation of our interest in sulfur chemistry,12 we herein
wish to report a protocol for the synthesis of disulfides in aqueous
media.
RESULTS AND DISCUSSION
Initially, we investigated the synthesis of phenyl disulfide in the pres-
ence of benzenesulfonyl chloride at room temperature under different
conditions, and the results are listed in Table I.
TABLE I Synthesis of Phenyl Disulfide Under Different Reaction
Conditionsa
Entry
R
Reaction medium
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
9
C6H5
p-CH3C6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
Pyridine
120
120
120
120
120
30
30
10
10
10
0
0
80
10
0
30
65
95
96
95
95
Pyridine11
Triethyl amine
H2O
HCl/ H2O (0.1 mol/L)
NaOH/H2O (0.01 mol/L)
NaOH/H2O (1 mol/L)
NaOH/H2O (2.5 mol/L)
NaHCO3/H2O (Saturated)
Na2CO3/H2O (Saturated)
NaHCO3/H2O (Saturated)
10
11
C6H5
p-CH3C6H4
10
aThe reactions were performed starting from thiophenol (1 mmol) and sulfonyl chlo-
ride (0.5 mmol) in reaction medium (5 mL) at room temperature.
bIsolated yields.

Disulfide Synthesis Promoted by Sulfonyl Chloride
2555
TABLE II Synthesis of Phenyl Disulfide in the Saturated NaHCO3 So-
lution at Room Temperaturea
Sulfonyl Chloride
(equiv.)
V/solvent
(mL)
Entry
Yield (%)b
1
2
3
4
5
6
7
8
9
0.1
0.2
0.3
0.4
0.5
0.6
0.7
1.0
1.5
0.6
0.6
0.6
2
2
2
2
2
2
2
2
2
1
3
5
21
42
56
85
91
96
95
96
97
96
95
96
10
11
12
aReaction conditions: thiophenol (1 mmol), room temperature, 10 min.
bIsolated yields.
Surprisingly, it was found that the phenyl disulfide (2a) was pro-
duced exclusively with excellent yields in alkaline aqueous media, such
as NaOH/H2O (2.5 mol/L), saturated NaHCO3/H2O, and Na2CO3/H2O
for 10 min. However, a trace of 2a was obtained using pyridine as sol-
vent at the room temperature.13 Encouraged by the results, subsequent
studies were carried out to optimize the reaction. The results were sum-
marized in Table II. It should be noted that 0.6 equiv benzenesulfonyl
chloride and 1 mL solvent were efficient enough to promote the re-
action. Increasing the amount of catalysts did not improve the yield
significantly (Table II, entries 7–9). Finally, we achieved an optimized
condition using 0.6 equiv benzenesulfonyl chloride in 1 mL saturated
NaHCO3/H2O solution at room temperature.
In the next stage, we studied the reaction scope for the synthesis of
disulfides from various commercially available mercaptan derivatives
under the optimized conditions (Table III).
As expected, this reaction proceeded smoothly, and the desired prod-
ucts were obtained with yields ranging from good to excellent. A

2556
H. Xiao et al.
TABLE III Synthesis of Disulfidesa
Entry
R
Product
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
Yield (%)b
97
Found Mp (◦C) (Lit.)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
C6H5
55–57 (58–60)15a
38–40 (45–46)15b
4-CH3C6H4
2-CH3C6H4
3-CH3C6H4
2,4-(CH3)2C6H3
2-CH3CH2C6H4
4-(CH3)2CHC6H4
4-BrC6H4
96
91
90
98
93
90
83
89
94
95
94
91
86
95
94
82
Liquid15c
c
Liquid15d
Liquid15e
Liquid15f
d
e
f
Liquid15g
g
89–90 (88–90)15b
68–70 (70–73)15h
4-ClC6H4
4-FC6H4
Liquid15i
i
4-OHC6H4
145–147 (149–150)15j
87–88 (93)15k
2-NH2C6H4
2,3-(Cl)2C6H3
4-CH3OC6H4CH2
4-ClC6H4CH2
2-ClC6H4CH2
2-BrC6H4CH2
2m
2n
2o
2p
2q
144–146 (no report)15l
91–93 (99)15m
50–52 (58–59)15c
85–87 (89–90)15n
66–68 (86–88)15o
aReaction conditions: thiophenol (1 mmol), sulfonyl chloride (0.6 mmol), saturated
NaHCO3 solution (1 mL), room temperature, 10 min.
bIsolate yields.
series of mercaptans with electron-donating or electron-withdrawing
groups attaching to the aromatic ring were investigated. The substitu-
tion groups on the aromatic ring have no obvious effect on the yields
(Table III, entries 2–4). Moreover, it is observed that the desired prod-
ucts 2n–2q were obtained from aliphatic mercaptans in good yields
(Table III, entries 14–17). When the substrates bearing different nu-
cleophilic groups such as 4-mercaptophenol and 2-aminobenzenethiol
were used, interestingly, the reaction was completed with nucleophilic
attack of the thiohydroxy, and the hydroxy or amino group remained
untouched (Table III, entries 11–12). The easy isolation of final prod-
ucts by either filtration or extraction from the crude mixtures rendered
this method practical in industrial applications.
A tentative mechanism for the formation of disulfides was proposed
in Scheme 1. We propose that the reaction involves two steps. In the first

Disulfide Synthesis Promoted by Sulfonyl Chloride
2557
step, one molecule of mercaptans 1 reacts with benzenesulfonyl chlo-
ride and produces the thiolsulfonates 3. In the second step, the other
molecule of 1 reacts with 3 and delivers disulfides 2 at the expense
of the thiolsulfonates in the alkaline aqueous solution. The initially
formed thiolsulfonates are more reactive with thiophenol than the ben-
zenesulfonyl chloride (K2ꢀK1),14 so the reaction produces disulfides
exclusively. The NaHCO3 plays a role to eliminate the byproduct of
acids.
EXPERIMENTAL
All products were known compounds and identified by comparison with
authentic samples. Melting points were measured on Digital Melt-
ing Point Apparatus WRS-1B and are uncorrected. IR spectra were
1
recorded on a Avatar 370 FI-infrared spectrophotometer. All H and
13C NMR spectra were recorded on a Bruker Avance 300 MHz spec-
trophotometer in CDCl3 or DMSO-d6 as a solvent with TMS as the
internal standard. J values are given in Hz.
General Procedure
To a mixture of saturated NaHCO3 solution (1 mL) and thiophenol (1
mmol), benzenesulfonyl chloride (0.5 mmol) was added. The mixture
was stirred at room temperature for 10 min, and the reaction mixture
was extracted with ethyl acetate (3 × 5 mL). The combined organic lay-
ers were washed with water and dried over sodium sulfate. The organic
layer was concentrated under reduced pressure to afford crystalline (or
liquid) dialkyl disulfides. The pure liquid products were obtained by
purification on a short silica gel column using petroleum ether as the
eluent. The pure solid products were obtained by purification recrys-
tallization from ethanol.
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