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Published on the web March 6, 2010
CAN/I2-catalyzed Chemoselective Synthesis of Thiosulfonates by Oxidation of Disulfides or Thiols
Ming-Tiao Cai,1 Guang-Shu Lv,1 Jiu-Xi Chen,*1 Wen-Xia Gao,1 Jin-Chang Ding,1,2 and Hua-Yue Wu*1
1College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, P. R. China
2Wenzhou Vocational and Technical College, Wenzhou 325035, P. R. China
(Received January 20, 2010; CL-100058; E-mail: jiuxichen@wzu.edu.cn, huayuewu@wzu.edu.cn)
Table 1. Screening conditions for the oxidation of diphenyl
disulfidea
CAN/I2 promoted synthesis of thiosulfonates by oxidation
of disulfides and thiols with high chemoselectivity and excellent
yields in wet poly(ethylene glycol) (PEG-400). The overall
process is simple, practical, and it provides convenient access to
thiosulfonates.
O
S S
S S
O
1a
3a
Entry
CAN/mol %
Time
Yieldb/%
Thiosulfonates, with strong sulfenylating power, have found
wide industrial applications both in polymer production and in
photographic processes.1 One of the most practically and widely
used routes for the synthesis of thiosulfonates involve the direct
oxidation of disulfides in the presence of various promoting
agents, such as benzenesulfinate/bromine,2 sodium trifluoro-
methanesulfinate/[bis(trifluoroacetoxy)iodo]benzene,3 dinitro-
gen tetroxide/charcoal,4 dinitrogen tetroxide supported on
poly(vinylpyrrolidone),5 tetrabutylammonium peroxymonosul-
fate,6 and Re(Ph2SO).7 In another method, thiosulfonates have
been prepared by tandem reaction of thiols under oxidative
conditions.5-8 Some other methods include selective reduction of
arenesulfonyl chlorides promoted by samarium metal in DMF.9
However, many of these processes suffer limitations, such as use
of volatile organic solvents and strong oxidizing agents, drastic
reaction conditions, expensive reagents, unsatisfactory yields,
tedious workup procedures, and co-occurrence of several side
reactions. As a consequence, the introduction of new methods
and/or further work on technical improvements to overcome the
limitations is still an important experimental challenge.
Ceric ammonium nitrate (CAN), as a very inexpensive and
easily available oxidizing agent, has been widely used in organic
reactions,10 but it has not been carefully studied as a catalyst in
the synthesis of thiosulfonates until now. CAN is a one-electron
transfer reagent and has a high molecular weight, therefore,
a large quantity of CAN is required for a reaction utilizing
stoichiometric amounts of CAN reagent. To circumvent this
limitation, several synthetic protocols have benn reported,11
stoichiometric CAN has been replaced with a dual oxidant
system consisting of a catalytic amount of CAN and another
oxidant. The purpose of the co-oxidant is to regenerate Ce(IV)
oxidant to continue the desired oxidation activity. I2 as an
oxidant has been used extensively due to its inherent properties
of low toxicity, and easy handling. During this research, we
found that CAN could catalyze synthesis of thiosulfonates in the
presence of I2. PEG is known to be inexpensive, thermally
stable, recoverable, biological compatible, and nontoxic,12 so we
decided to use PEG as the reaction media for the synthesis of
thiosulfonates.
1
2
3
4
5
6
7
8
9
0
5
24 h
19 h
24 h
24 h
75 min
75 min
75 min
16 h
10 h
24 h
0
65
20
20
20
20
20
10
15
20
20
35c
traced
99
96e
99f
97
98
80g
traceh
10
11
75 min
a1a (1 mmol), I2 (1.5 equiv), 4 mL of PEG-400/H2O = 3:1 (v/v),
b
c
d
60 °C, see Ref. 14. Isolated yield. PEG-400 as solvent. H2O as
solvent. eWith 1 equiv of I2. With 2 equiv of I2. gWithout I2.
f
hUnder N2 atmosphere.
The model oxidation reaction of 1,2-diphenyldisulfide (1a)
was conducted to screen the optimal reaction conditions
(Table 1). In our initial studies, we evaluated the feasibility of
oxidation of disulfides to thiosulfonates in PEG utilizing the
CAN/I2 dual oxidant system. As expected, the reaction provided
the desired product 3a in 35% isolated yield. Encouraged by this
promising result, we further optimized the reaction conditions
including reaction temperature, and the amount of CAN and I2.
Recently, Firouzabadi and Iranpoor,15 have reported the con-
version of organic halides to symmetric disulfides in PEG and
water solvent system. Enlightened by research, we investigated
the transformation cyclocondensation reaction in the combina-
tion of PEG and water solvent system. The volume ratio of PEG
and water was examined and the best results were obtained by
carrying out the reaction in PEG-400/H2O with a ratio of 3:1
(v/v). One likely reason was that water was necessary to
dissolve CAN since it has limited solubility in PEG.
The role of I2 co-oxidant utilized in this procedure is to
regenerate the Ce(IV) species which oxidizes disulfides to
thiosulfonates. That the actual oxidant is Ce(IV) and not I2 was
confirmed in control experiments, wherein the absence of Ce(IV)
resulted in an extremely sluggish reaction insufficient for
complete product formation even after 24 h. (Entry 1). The rate
of oxidation reaction in the presence of 5 mol % of CAN was
extremely slow (Entry 2). Increasing the amount of CAN to
20 mol % in the system increased the yield rapidly and produced
a quantitative yield of 3a (Entry 5). Although as low as 10 mol %
of CAN is capable of oxidizing disulfides to thiosulfonates in
In continuation of our research in developing novel synthetic
routes for the formation of carbon-sulfur bonds,13 in this study
we wish to report the use of a catalytic redox cycling for the
synthesis of various thiosulfonate derivatives, based on [Ce(IV)/
Ce(III)]-redox-mediated oxidation of disulfides and thiols.
Chem. Lett. 2010, 39, 368-369
© 2010 The Chemical Society of Japan