Green preparation of disulfides from corresponding thiols by poly(4-vinylpyridinium nitrate) as recoverable and new polymeric reagent

Article abstract of DOI:10.1080/17415993.2010.541462

Poly(4-vinylpyridinium nitrate) was found to be a recyclable and highly efficient oxidizing polymer for the oxidative coupling of a variety of aliphatic or aromatic thiols to the corresponding disulfides. Poly(4-vinylpyridinium nitrate) is an extremely mild agent, which gave no other oxidized side products.

Full text of DOI:10.1080/17415993.2010.541462

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Green preparation of disulfides
from corresponding thiols by poly(4-
vinylpyridinium nitrate) as recoverable
and new polymeric reagent
Arash Ghorbani-Choghamarani a & Sara Sardari b
a Department of Chemistry, Faculty of Science, Ilam University, PO
Box 69315516, Ilam, Iran
b Islamic Azad University, Branch-Omidiyeh, Ahvaz, Iran
Version of record first published: 21 Dec 2010.
To cite this article: Arash Ghorbani-Choghamarani & Sara Sardari (2011): Green preparation of
disulfides from corresponding thiols by poly(4-vinylpyridinium nitrate) as recoverable and new
polymeric reagent, Journal of Sulfur Chemistry, 32:1, 63-69
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Journal of Sulfur Chemistry
Vol. 32, No. 1, February 2011, 63–69
Green preparation of disulfides from corresponding thiols by
poly(4-vinylpyridinium nitrate) as recoverable and new
polymeric reagent
Arash Ghorbani-Choghamarania* and Sara Sardarib
aDepartment of Chemistry, Faculty of Science, Ilam University, PO Box 69315516, Ilam, Iran; bIslamic
Azad University, Branch-Omidiyeh, Ahvaz, Iran
(Received 26 September 2010; final version received 16 November 2010)
Poly(4-vinylpyridinium nitrate) was found to be a recyclable and highly efficient oxidizing polymer for
the oxidative coupling of a variety of aliphatic or aromatic thiols to the corresponding disulfides. Poly(4-
vinylpyridinium nitrate) is an extremely mild agent, which gave no other oxidized side products.
H2
C
H
C
n
+
N
-
N
S
N
S
N
S
H NO3
S
S
SH
Conditions:
A or B
A: Silica sulfuric acid, ethyl acetate, r.t.
B: Acetonitrile, r.t.
Keywords: thiols; disulfides; poly(4-vinylpyridine); poly(4-vinylpyridinium nitrate); coupling
1. Introduction
In the last few years, supported reagents on polymers have become increasingly applied in organic
synthesis (1–5), because the reactions are carried out under mild conditions. Disulfide bonds play
crucial roles in biology and chemistry (6). Oxidation of thiols is the most exploited method for
disulfide synthesis mainly because a large number of thiols are commercially available and/or are
easily synthesized (7). The controlled oxidative coupling of thiols to disulfides is of great interest
and oxidative coupling of thiols to disulfides under mild conditions is of practical importance
*Corresponding author. Email: arashghch58@yahoo.com or a.ghorbani@mail.ilam.ac.ir
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2010.541462
http://www.informaworld.com

64 A. Ghorbani-Choghamarani and S. Sardari
in synthetic methodology. In the last decade, variable methodologies have been studied for the
conversion of thiols into disulfides (8–20), but some of these methods have several disadvantages
such as overoxidation, tedious work-up, low yields of products, heavy metal contamination, harsh
conditions, and expensive reagents or catalysts. Therefore, to improve the mentioned limitations,
we decided to design a new system for this transfromation.
2. Results and discussion
In continuation of our studies on the application of new reagents or reagent systems in organic
reactions (21–27), we became interested to explore a new methodology for the fine and selective
conversion of thiols into disulfides. In this light, we decided to prepare a mild oxidizing agent
based on oxidizing properties of nitric acid. Therefore, we prepared a polymeric nitrate salt via a
reaction of nitric acid (65%) with poly(4-vinylpyridine) (Scheme 1).
H2
C
H2
C
H
C
H
C
HNO3
n
n
+
N
N
-
H NO3
Scheme 1. Preparation of poly(4-vinylpyridinium nitrate).
Based on our previous studies, we assumed that the oxidizing properties of this polymeric
nitrate salt could be increased in the presence of an acid. Consequently, we have examined a
variety of solid acids for this purpose (Scheme 2 and Table 1).
H2 H
C
C
n
+
N
N
S
N
S
N
S
-
H NO3
S
S
SH
Solid acid
MeCOOEt, r.t.
Scheme 2. Oxidative coupling of 2-mercaptobenzothiazole in the presence of different solid
acids.
As the results show, all of the mentioned solid acids in Table 1 are applicable for the coupling
reaction, but we decided to use silica sulfuric acid because of (a) shorter reaction time, (b) higher
purity of produced disulfide (based on resulting melting points), and (c) metal-free content of
this acid.
Certainly, solvent plays a critical role in the reactions; therefore, we decided to investigate the
solvent effect and select an appropriate solvent for the oxidative coupling of thiols into disulfides.
Therefore, we screened different solvents for the preparation of 1,2-bis(2-benzoxazol)disulfane, as
a typical example, by poly(4-vinylpyridinium nitrate) and silica sulfuric acid in different solvents
at room temperature (Table 2).
Consequently, Table 2 shows that the best solvent for the oxidative coupling of thiols (by poly(4-
vinylpyridinium nitrate) and silica sulfuric acid) is ethyl acetate in terms of reaction kinetics.

Journal of Sulfur Chemistry 65
Table 1. Oxidative coupling of 2-mercaptobenzothiazole with poly(4-vinylpyridinium nitrate)
and solid acids in ethyl acetate at room temperature.a
Entry
Solid acid
Time (min)
Yield (%)b
Mp (◦C)c
1
2
3
4
5
6
7
8
9
Zn(HSO4)2
Ca(HSO4)2
Fe(HSO4)2
Citric acid
l-Alanine
NH2SO3H
Al(HSO4)3
KHSO4
10
10
10
40
40
25
5
35
45
10
99
99
96
99
99
99
99
99
96
97
160–164
160–165
168
163–168
171–174
160–165
165–168
175–179
170–171
176–178
NaHSO4
SiO2-OSO3H
10
Notes: aSubstrate/poly(4-vinylpyridinium nitrate)/acid for Entries 1–9 (1 mmol/0.338 g/2 mmol) for Entry 10
(1 mmol/0.338 g/0.2 g). bIsolated yield. cReported mp (177–179) (8).
Table 2. Oxidative coupling of 2-mercaptobenzothiazole using poly(4-vinylpyridinium
nitrate) and silica sulfuric acid in different solvents at room temperature.a
Entry
Solvent
Time (min)
Yield (%)b
1
2
3
4
5
6
Acetonitrile
Acetone
Chloroform
Dichloromethane
Ethyl acetate
Ethanol
45
270
145
45
10
360
99
90
95
91
97
c
–
Notes: aSubstrate/poly(4-vinylpyridinium nitrate)/silica sulfuric acid (1mmol/0.338 g/0.2 g). bIsolated
yield. cNo reaction.
With optimal conditions in hand, we investigated the coupling of a variety of aliphatic and
aromatic thiols into disulfides using poly(4-vinylpyridinium nitrate) and silica sulfuric acid in
ethyl acetate at room temperature (Scheme 3 and Table 3).
solid acids
H2 H
C C
n
+
N
-
H NO3
R–SH
RS–SR
Silica sulfuric acid
MeCOOEt, r.t.
1
2
COOH
Br
SH
SH
F
SH
H3C
SH
SH
HSCH2COOH
a
b
c
d
e
N
S
O
SH
SH
SH
N
N
N
f
g
h
i
Scheme 3. Coupling of thiols by poly(4-vinylpyridinium nitrate) and silica sulfuric acid.

66 A. Ghorbani-Choghamarani and S. Sardari
Table 3. Oxidative coupling of thiols into disulfides by poly(4-vinylpyridinium nitrate) I and silica sulfuric acid II
in ethyl acetate at room temperature.
Substrate/reagents
(mmol)a
Time
(min)
Yield
(%)b
Mp (◦C)
found
Mp (◦C)
reported
Entry
Substrate
Product
I
II
Reference
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
2a
2b
2c
2d
2e
2f
2g
2h
2i
0.338
0.338
0.338
0.338
0.338
0.338
0.338
0.338
0.338
0.338
0.2
0.4
0.2
0.4
0.4
0.4
0.4
0.4
0.2
0.0
95
25
10
80
60
97
99
99
95
90
91
99
87
97
90c
89–92
Oil
39–42
273–285
Oil
141–144
164–166
84–88
90–92
Oil
43–44
278–280
Oil
144–146
167–169
77.5–79
177–179
177–179
(8)
(22)
(8)
(22)
(22)
(8)
(12)
(22)
(8)
75
105
20 h
10
176–178
176–178
10
1i
2i
55
(8)
Notes: aI and II refer to grams of poly(4-vinylpyridinium nitrate) and silica sulfuric acid. bIsolated yield. cIn the absence of silica sulfuric
acid.
Reactions were carried out under completely heterogeneous conditions. After reaction com-
pletion, pure product was easily obtained by simple filtration, washing by ethyl acetate, and
evaporating the solvent.
In order to study the role of silica sulfuric acid, 2-mercaptobenzothiazole was subjected to
oxidative coupling by poly(4-vinylpyridinium nitrate) in the absence of silica sulfuric acid (as a
typical example). Interestingly, we observed that the reaction time increased to 55 min (Table 3,
Entry 10).Although silica sulfuric acid increases the rate of the reaction, fortunately this increased
time is not too much. Consequently, we decided to run all of the coupling reactions in the absence
of acid.
Initially, to find an appropriate solvent for this new condition, we screened different solvents
for the oxidative coupling of 2-mercaptobenzothiazole using poly(4-vinylpyridinium nitrate) as
a typical example (Table 4).
Table 4. Oxidative coupling of 2-mercaptobenzothiazole using poly(4-vinylpyridinium
nitrate) in the absence of silica sulfuric acid in different solvents at room temperature.a
Entry
Solvent
Time (min)
Yield (%)b
1
2
3
4
5
6
Acetonitrile
Acetone
Chloroform
Dichloromethane
Ethyl acetate
Ethanol
15
175
52
30
55
98
99
99
98
90
c
360
–
Notes: aSubstrate/poly(4-vinylpyridinium nitrate): (1 mmol/0.338 g). bIsolated yield. cNo reaction.
H2 H
C C
n
+
N
-
H NO3
R–SH
RS–SR
CH3CN, r.t.
1
2
Scheme 4. Coupling of thiols with poly(4-vinylpyridinium nitrate) in the absence of acid.

Journal of Sulfur Chemistry 67
Table 5. Oxidative coupling of thiols to corresponding disulfides with poly(4-vinylpyridinium nitrate) in acetonitrile at
room temperature.a
Entry
Substrate
Product
Time (Min)
Yield (%)b
Mp (◦C) found
Mp (◦C) reported
Reference
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
2a
2b
2c
2d
2e
2f
2g
2h
2i
150
230
110
160
70
150
380
25
99
91
99
90
87
95
Sluggish
97
88–93
Oil
40–42
277–285
Oil
139–142
–
84–90
177–180
90–92
Oil
43–44
278–280
Oil
144–146
–
77.5–79
177–179
(8)
(22)
(8)
(22)
(22)
(8)
–
(22)
(8)
15
98
Notes: aSubstrate/poly(4-vinylpyridinium nitrate) for Entries 1–5 and 7–9 (1 mmol/0.338 g); for Entry 6 (1 mmol/0.507 g). bIsolated yield.
Table 6. Recoverability of poly(4-vinylpyridinium nitrate)
for the coupling of 2-mercaptobenzothiazole.
Run no.
Time (min)
Yield (%)a
1
2
3
4
5
15
10
9
12
11
99
95
97
98
98
Note: aIsolated yield.
The results show that the appropriate solvent for the oxidative coupling of thiols by poly(4-
vinylpyridinium nitrate) in the absence of solid acids is different from the reaction in the presence
of acid. Therefore, the best choice for the new conditions is acetonitrile. Eventually, all of the
thiols were subjected to the oxidative coupling by poly(4-vinylpyridinium nitrate) in the absence
of any acid (Scheme 4 and Table 5).
The important advantage of the coupling reaction using poly(4-vinylpyridinium nitrate) without
any additive is the recoverability of the poly(4-vinylpyridinium nitrate).After reaction completion,
poly(4-vinylpyridine) can be easily isolated by simple filtration. It could be converted into poly(4-
vinylpyridinium nitrate) by reaction with nitric acid again. As is evident from Table 6, recycled
Scheme 5. Mechanism of the oxidative coupling of thiols.

68 A. Ghorbani-Choghamarani and S. Sardari
poly(4-vinylpyridinium nitrate) is reusable for five times and its activity dose not show any
significant decrease.
The proposed mechanism for the oxidative coupling of thiols into disulfides by described
systems is outlined in Scheme 5.
3. Conclusion
In summary, in this research, a new oxidizing polymer has been introduced for the preparation of
disulfides in the presence of solid acids in the absence of any acid under mild and heterogeneous
conditions. Poly(4-vinylpyridinium nitrate) is a recoverable, metal-free and non-toxic polymeric
oxidizing agent, which could be recognized as a new and green organic agent.
4. Experimental
The chemicals and solvents were purchased from Fluka, Merck, and Aldrich chemical companies
without further purifications. All products are known and were characterized by comparison of
their spectral (IR, 1H NMR, or 13C NMR) and physical data with authentic samples.
4.1. Preparation of poly(4-vinylpyridinium nitrate)
In a 50 ml round-bottomed flask, 2 ml of HNO3 (65%) and 3.03 g of poly(4-vinylpyridine) was
stirred for 1 h, then kept at 50◦C for 48 h to obtain dry poly(4-vinylpyridinium nitrate) as a white
crystalline solid quantitatively.
4.2. Oxidative coupling of 2-mercaptobenzoxazole into 1,2-bis(2-benzoxazol)disulfane
using poly(4-vinylpyridinium nitrate) and silica sulfuric acid: as a typical procedure
Poly(4-vinylpyridinium nitrate) (0.338 g) and silica sulfuric acid (0.2 g) was added to a solution
of 2-mercaptobenzoxazole (0.167 g, 1 mmol) in ethyl acetate (10 ml). The resulting mixture was
stirred at room temperature for 10 min (the reaction progress was monitored by TLC) and then
filtered. The residue was washed with ethyl acetate (4 × 5 ml). Finally, the solvent was removed
and 1,2-bis(2-benzoxazol)disulfane was obtained in 97% yield (0.323 g) as a crystalline white
solid; mp 176–178◦C (Lit. (8) 177–179◦C).
4.3. Oxidative coupling of 2-mercaptobenzoxazole using poly(4-vinylpyridinium nitrate)
without solid acid: as a typical procedure
Poly(4-vinylpyridinium nitrate) (0.338 g) was added to a solution of 2-mercaptobenzoxazole
(0.167 g, 1 mmol) in acetonitrile (10 ml). The resulting mixture was stirred at room tempera-
ture for 15 min (the reaction progress was monitored by TLC) and then filtered. The residue
was washed with acetonitrile (4 × 5 ml). Finally, the solvent was evaporated and 1,2-bis(2-
benzoxazol)disulfane was obtained in 98% yield (0.326 g) as a crystalline white solid; mp
177–180◦C (Lit. (8) 177–179◦C).
Acknowledgement
This work was supported by the research facilities of Ilam University, Ilam, Iran.

Journal of Sulfur Chemistry 69
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