Selective and convenient oxidation of thiols to disulfides using n-butyltriphenylphosphonium dichromate (Bun PPh3) 2Cr2O7 in solution, under solvent-free conditions and microwave irradiation

Article abstract of DOI:10.1080/10426500490485020

A variety of aliphatic, aromatic, and heteroaromatic thiols were rapidly and cleanly converted to their corresponding disulfides in excellent yields using n-butyltriphenylphosphonium dichromate (BTPPDC) in acetonitrile solution under solvent-free conditions and microwave irradiation. Selective oxidation of thiols in the presence of other oxidizable functional groups, such as alcohol and sulfide, is a noteworthy advantage of this method.

Full text of DOI:10.1080/10426500490485020

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SELECTIVE AND CONVENIENT
OXIDATION OF THIOLS
TO DISULFIDES USING n-
BUTYLTRIPHENYLPHOSPHONIUM
n
DICHROMATE (Bu PPh ) Cr O
3
2
2 7
IN SOLUTION, UNDER SOLVENT-
FREE CONDITIONS AND
MICROWAVE IRRADIATION
a
Iraj Mohammadpoor-Baltork , Hamid Reza
a
a
Memarian & Kiumars Bahrami
a
Department of Chemistry, Isfahan University ,
Isfahan, Iran
Published online: 16 Aug 2010.
To cite this article: Iraj Mohammadpoor-Baltork , Hamid Reza Memarian &
Kiumars Bahrami (2004) SELECTIVE AND CONVENIENT OXIDATION OF THIOLS TO
n
DISULFIDES USING n-BUTYLTRIPHENYLPHOSPHONIUM DICHROMATE (Bu PPh ) Cr O
3
2
2
7
IN SOLUTION, UNDER SOLVENT-FREE CONDITIONS AND MICROWAVE IRRADIATION,
Phosphorus, Sulfur, and Silicon and the Related Elements, 179:11, 2315-2321, DOI:
0.1080/10426500490485020
1
To link to this article: http://dx.doi.org/10.1080/10426500490485020
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Phosphorus, Sulfur, and Silicon, 179:2315–2321, 2004
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490485020
SELECTIVE AND CONVENIENT OXIDATION
OF THIOLS TO DISULFIDES USING
n-BUTYLTRIPHENYLPHOSPHONIUM DICHROMATE
n
(
Bu PPh ) Cr O IN SOLUTION, UNDER
3
2
2
7
SOLVENT-FREE CONDITIONS AND
MICROWAVE IRRADIATION
Iraj Mohammadpoor-Baltork, Hamid Reza Memarian,
and Kiumars Bahrami
Department of Chemistry, Isfahan University, Isfahan, Iran
(
Received May 2, 2004; accepted July 5, 2004)
A variety of aliphatic, aromatic, and heteroaromatic thiols were rapidly
and cleanly converted to their corresponding disulfides in excellent
yields using n-butyltriphenylphosphonium dichromate (BTPPDC) in
acetonitrile solution under solvent-free conditions and microwave irra-
diation. Selective oxidation of thiols in the presence of other oxidizable
functional groups, such as alcohol and sulfide, is a noteworthy advan-
tage of this method.
Keywords: Dichromate; disulfides; oxidation; thiols
INTRODUCTION
Selective oxidative conversion of thiols to disulfides is of interest from
1
,2
both a biological and a synthetic point of view. Many methods and
reagents for the oxidation of thiols to disulfides have been reported in
3
−21
the literature.
Some of these methods suffer from one or more of the
following disadvantages; long reaction times; difficult workup; lack the
general applicability to thiol substrates bearing alkyl, aryl, and hete-
rocyclic moieties; and formation of overoxidation products, leading to
lower yields, oxidation of other functional groups in the presence of
thiol group, and the use of stoichiometric and excess amounts of the
reagents for successful oxidation. Thus, there is still a need to develop
We thank the Isfahan University Research Council for partial support of this work.
Address correspondence to Iraj Mohammadpoor-Baltork, Department of Chemistry,
Isfahan University, Isfahan 81746-73441, Iran. E-mail: imbaltork@sci.ui.ac.ir
2
315

2
316
I. Mohammadpoor-Baltork et al.
a mild and efficient methodology to synthesize aliphatic, aromatic, and
heteroaromatic disulfides. In this respect, we wish to report that n-
butyltriphenylphosphonium dichromate (BTPPDC) is able to transform
different types of thiols to their corresponding disulfides efficiently un-
der different reaction conditions.
RESULTS AND DISCUSSION
n-Butyltriphenylphosphonium dichromate (BTPPDC) is an inexpensive
and easily prepared reagent. Several synthetically useful organic trans-
formations using this reagent have been reported previously.22,23 In this
article the oxidative coupling of thiols with this reagent was investi-
gated in solution under solvent-free conditions and microwave irradia-
tion (Scheme 1).
SCHEME 1
We first examined the oxidative coupling of 2-mercaptopyrimidine
(
Table I, entries 22–24) as a model substrate in the presence of BTPPDC
for 2 min in solution, under solvent-free conditions and microwave ir-
radiation, and the corresponding disulfide was obtained in 10, 15, and
93% yields, respectively. Therefore, to obtain high yields of the products
in solution and under solvent-free conditions, longer reaction times are
required. The oxidation of 2-mercaptopyrimidine was also investigated
in various solvents such as CH3CN, CHCl3, CH2Cl2, Tetrahydrofuran
(
THF), and n-hexane at room temperature for 75 min, and the corre-
sponding disulfide was isolated in 90, 75, 40, 45, and 5% yields, re-
spectively. These results show that CH3CN can be used as a suitable
solvent for oxidation of thiols (method A). As shown in Table I, treat-
ment of a variety of thiols with 0.5 molar equivalent of BTPPDC in
acetonitrile at room temperature afforded the corresponding disulfides
in 90–95% yields within 30–120 min. Under solvent-free conditions,
these reactions proceeded within 6–18 min in the presence of 0.5 molar
equivalent of the reagent, and the corresponding disulfides were ob-
tained in 90–95% yields. Finally, the oxidative coupling was carried out

n
Thiols to Disulfides Using (Bu PPh ) Cr
O
7
2317
3
2
2
a
TABLE I Oxidation of Thiols to Disulfides with BTPPDC
Methodb
Time (min)
Yield (%)c
M.p. ( C)
◦
9,13,17
Entry
R
1
2
3
4
5
6
7
8
9
0
1
2
3
Ph
Ph
Ph
A
B
C
A
B
C
A
B
C
A
B
C
A
45
8
1
30
6
0.75
60
10
1.5
60
10
1.5
90
95
95
96
93
91
95
94
92
94
92
92
93
92
57–58
—
—
45–47
—
—
90–92
—
—
74–75
—
—
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
1
1
1
1
142–143
1
1
1
1
1
1
4
5
6
7
8
9
B
C
A
B
C
A
15
2
91
93
91
91
93
92
—
—
45
8
Oil
—
1
—
60
54–55
2
2
0
1
B
C
10
91
95
—
—
1.5
2
2
2
2
2
2
2
3
4
5
6
7
A
B
C
A
B
C
75
12
2
90
92
93
92
92
94
140–143
—
—
120
18
3
181–183
—
—
(
Continued on next page)

2
318
I. Mohammadpoor-Baltork et al.
a
TABLE I Oxidation of Thiols to Disulfides with BTPPDC
(Continued)
Methodb
Time (min) Yield (%)c
◦
M.p. ( C)
9,13,17
Entry
R
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
PhCH2
PhCH2
PhCH2
c-C6H11
c-C6H11
c-C6H11
n-C8H17
n-C8H17
n-C8H17
n-C4H9
n-C4H9
n-C4H9
HOCH2CH2
HOCH2CH2
HOCH2CH2
A
B
C
A
B
C
A
B
C
A
B
C
A
B
C
30
7
1
45
9
1.5
80
12
2
40
8
1.25
40
8
90
91
94
92
90
90
90
91
93
91
92
94
90
93
93
69–70
—
—
Oil
—
—
Oil
—
—
Oil
—
—
Oil
—
—
1
aAll products were characterized by comparison of their spectral and
physical data with those of authentic samples.
b
Method A = Thiol:BTPPDC, 1:0.5, CH3CN (10 ml per mmol of thiol);
Method B = Thiol:BTPPDC, 1:0.5, solvent-free; Method C = Thiol:BTPPDC,
1
:0.4, MW.
cIsolated yields of pure disulfides.
under microwave irradiation in the presence of 0.4 molar equivalent of
BTPPDC, with reaction periods ranging between 0.75–3 min, and the
pure products were obtained in 90–96% yields. Under microwave irradi-
ation, acetonitrile was used for homogenization of the reaction mixture.
The polar character of this solvent also seems to increase the reaction
temperature, so the reaction is completed in a short time.24 The results
show that the yields of the products are comparable under the three
above mentioned conditions, but the reaction times are considerably
shorter under microwave irradiation.
It is important to note that in oxidation of 2-mercaptoethanol
(
Table I, entries 40–42), only mercaptan functionality was converted
to disulfide, and the hydroxy group remained intact in the reaction
mixture. Another noteworthy advantage of this reagent is the exclu-
sive oxidation of thiols in the presence of sulfides. When an equimolar
mixture of thiol and sulfide was treated with BTPPDC, only the thiol
was selectively oxidized to the corresponding disulfide, and sulfide re-
mained unchanged (Table II).
In summary, we have introduced n-butyltriphenylphosphonium
dichromate as an inexpensive and effective reagent for the oxidation
of thiols to disulfides. In addition, high yields of the products, easy

n
Thiols to Disulfides Using (Bu PPh ) Cr
O
7
2319
3
2
2
TABLE II Selective Oxidation of Thiols in the Presence of
Sulfides with BTPPDC
Yield%a (time/min)
Entry
1
Substrate
Product
Solution
91(60)
Solvent-free
90(10)
MW
93(1.5)
PhSCH2Phb
PhSMeb
—
—
—
—
92(60)
—
91(10)
—
92(1.5)
2
3
—
91(60)
—
91(10)
—
94(1.5)
n-BuSBu-nb
—
—
—
a
Isolated yields of pure disulfides.
Sulfide remained intact in the reaction mixture.
b
workup, and selective oxidation of thiols in the presence of alcohol and
sulfide are noteworthy advantages of this method.
EXPERIMENTAL
General Procedure for the Oxidative Coupling
of Thiols in Acetonitrile
In a round-bottomed flask (50 ml), a solution of thiol (2 mmol) in
CH3CN (20 ml) was prepared. n-Butyltriphenylphosphonium dichro-
mate (0.854 g, 1 mmol) was added to the solution, and the reaction mix-
ture was stirred at room temperature for 30–120 min. The progress of
the reaction was monitored by thin layer chromatography (TLC; eluent:
n-hexane/ethyl acetate, 4:1). After completion of the reaction, the re-
action mixture was filtered and the solid material was washed with
CH3CN (10 ml). Evaporation of the solvent followed by recrystalliza-
tion or chromatography on silica gel with appropriate eluent afforded
the pure disulfides in 90–95% yields (Table I).
General Procedure for the Oxidative Coupling of Thiols
under Solvent-Free Conditions
A mixture of thiol (2 mmol) and n-butyltriphenylphosphonium dichro-
mate (0.854 g, 1 mmol) in a mortar was ground with a pestle for 6–
18 min. The progress of the reaction was monitored by TLC. After com-
pletion of the reaction, the mixture was extracted with CH2Cl2. The

2
320
I. Mohammadpoor-Baltork et al.
solvent was evaporated and the crude product was either recrystallized
or subjected to chromatography on silica gel with appropriate eluent to
afford the pure products in 90–95% yields (Table I).
General Procedure for the Oxidative Coupling of Thiols
under Microwave Irradiation
Thiol (2 mmol) and n-butyltriphenylphosphonium dichromate (0.683 g,
0.8 mmol) were mixed and then CH3CN (2 ml) was added. The mixture
was subjected to microwave irradiation at 900 W for 0.75–3 min. The
progress of the reaction was monitored by TLC. After completion of
the reaction, the mixture was extracted with CH2Cl2. The solvent was
evaporated, and the resulting crude material was either recrystallized
or subjected to chromatography on silica gel with appropriate eluent to
afford the pure products in 90–96% yields (Table I).
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O
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