Tungstate sulfuric acid: A novel and efficient solid acidic reagent for the oxidation of thiols to disulfides and the oxidative demasking of 1,3-dithianes

Article abstract of DOI:10.1080/10426500600864965

Tungstate sulfuric acid in combination with various oxidants was found to be an efficient reagent for the conversion of thiols to disulfides at r.t. in good to excellent yields. The selective oxidative deprotection of 1,3-dithianes to their parent carbonyl compounds at r.t. was also observed with this reagent. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500600864965

Phosphorus, Sulfur, and Silicon, 181:2825–2831, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600864965
Tungstate Sulfuric Acid: A Novel and Efficient Solid
Acidic Reagent for the Oxidation of Thiols to Disulfides
and the Oxidative Demasking of 1,3-Dithianes
Bahador Karami
Morteza Montazerozohori
Department of Chemistry, Yasouj University, Yasouj, Iran
Mohammad Hossein Habibi
Department of Chemistry, Isfahan University, Isfahan, Iran
Tungstate sulfuric acid in combination with various oxidants was found to be an
efficient reagent for the conversion of thiols to disulfides at r.t. in good to excellent
yields. The selective oxidative deprotection of 1,3-dithianes to their parent carbonyl
compounds at r.t. was also observed with this reagent.
Keywords 1,3-dithianes; disulfides; oxidation; thiols; tungstate sulfuric acid
INTRODUCTION
Currently, the heterogenation of chemical systems is an active field
in industrial and laboratorial chemistry because of the simplification
of handling procedures, reduction of corrosion, green chemistry point
of view, avoidance of byproducts, easy and clean reaction, and simple
work-up. With regard to the wide application of acids as reagents or cat-
8
alysts in organic chemistry (for producing more than 1 × 10 mt/year
of products), the introduction of new inorganic solid acids can be use-
1
2
ful. Recently, silica sulfuric acid and Nafion-H have been used for
a wide variety of reactions, such as the production of disulfides from
3
thiols; the oxidation of 1,4-dihydropyridines; the N-nitrosation of sec-
4
5
6
ondary amines; the deprotection of acetals; the oxidation of alcohols,
Received; accepted.
The authors gratefully acknowledge partial support of this work by the Yasouj
University, Yasouj, Iran. We are also thankful to Malihe AI, Ome-Leila Ghasemi, Mahnaz
Farahi, and Leila Hatam, students of the Chemistry Department at Yasouj University.
Address correspondence to Bahador Karami, Yasouj University, Department of
Chemistry, Yasouj, 75914-353 Iran. E-mail: karami@mail.yu.ac.ir
2825

2
826
B. Karami et al.
and the alkylation with olefins, alkyhalides, alkyl esters, isomerization,
transalkylation, acylation, nitration, ether and ester synthesis, acetal
7
formation, and rearrangement chemistry.
Disulfides play an important role in chemical syntheses. In biolog-
ical systems, they control the cellular redox potential and prevent ox-
idative damage.8 Several methods based on oxidative S-S coupling
have been used for the synthesis of disulfides from thiols and pro-
tected thiols, including coupling with redox dyes, diazo compounds, sul-
foxides, halogens, H2O2, KMnO4/CuSO4, DMSO/I2, sodium perborate,
−9
−
10
[
Fe4S4(SR)4]2 , and electrochemical methods.
,3-dithiane and 1,3-dithiolane derivatives are versatile intermedi-
1
ates in the synthesis and interconversion of monocarbonyl and 1,2-
dicarbonyl compounds. Thioacetals are often used as protecting groups
for carbonyl compounds, particularly in multistep natural product syn-
theses, due to their stability toward both acidic and basic conditions.
Many procedures are available in the literature for preparing thioac-
etals, but their deprotection to the parent carbonyl compounds is not al-
ways an easy process. In recent years, various hydrolytic11 or oxidative
methods have been reported for dethioacetalizations, and in the last two
decades, numerous reagent combinations have been documented for
the deprotection of thioacetals. Recently, we reported several methods
for the deprotection of 1,3-dithianes under thermal and photochemical
1
2−14
conditions.
RESULTS AND DISCUSSION
In continuation of our studies15 on the application of inorganic solid
acids in organic synthesis, we have found that anhydrous sodium
tungstate reacts with chlorosulfonic acid (1:2 mole ratio) to give
Tungstate Sulfuric Acid (TSA) 1 as a new solid acid. The reaction is
performed easy in a clean manner and without any work-up (Scheme 1).
After the preparation of TSA 1, we were interested to examine it
as a proton source in combination with various oxidants in organic
solvents. In this work we report a simple and practical method for
SCHEME 1

Tungstate Sulfuric Acid
2827
SCHEME 2
the effective oxidation of thiols to disulfides and for demasking 1,3-
dithianes under mild and heterogeneous conditions. A variety of thiols
were subjected to oxidation in the presence of wet 1 (10% w/w)/NaNO2
in dichloromethane. Oxidation reactions were performed under mild
and heterogeneous conditions. Immediately after the addition of the
reactants in dichloromethane, a light-green color of the solution was
observed, which disappeared quickly. We suggest that thionitrite 2
was formed, which converted to the related disulfides due to its in-
stability under the reaction conditions. Based on other reports in the
1
,16−17
literature,
we propose that the reaction proceeds via the thiyl
radicals 3 as reactive intermediates, with the formation of the disulfide
by coupling these radicals (Scheme 2).
The proposed mechanism shows that TSA 1 acts as a catalyst. For
increasing the rate of the reaction, we could use an excess of NaNO2,
but this was avoided because of probable nitrosation of the disulfides
(
Table I).
The ability of TSA 1 as a heterogeneous acidic reagent to catalyze the
oxidative demasking of 1,3-dithianes in the presence of an oxidant was
also investigated. The system consisting of wet 1 (10% w/w)/KMnO4
in dichloromethane was investigated for the deprotection of a variety
of 1,3-dithianes. The results showed that 1,3-dithianes undergo
oxidative cleavage by sulfoxidation1 and hydrolytic cleavage to yield
the related carbonyl compounds (Table II, Scheme 3). It was interesting
8

2
828

Tungstate Sulfuric Acid
2829
TABLE II The Oxidative Deprotection of 1,3-Dithianes With Wet
4
1/KmnO in Refluxing Dichloromethane
◦
b
M.P.( C)
R1
R2
Time (min.)
Yield (%)a
Found (Lit.)
2
4
4
-MeOC6H4
-Br-C6H4
-Cl-C6H4
H
Me
H
Ph
Me
CH2Br
H
H
H
Ph
120
70
55
70
60
30
120
60
93
95
90
95
95
94
91
95
92
93
33–35 (34–37)
49–50 (49–52)
44–46 (46)
47–48 (47–49)
116–118 (118–121)
106–108 (107–110)
42–43 (41–43)
57–58 (58)
Ph
4
4
2
3
4
4
-PhC6H4
-BrC6H4
-NO2C6H4
-NO2C6H4
-NO2C6H4
-Cl-C6H4
60
60
105–106 (106)
72–74 (73–75)
—
60
90
oil
—
H
40
30
80
81
oil
oil
C6H13
a
Refers to isolated yields.
b
Identified by comparison with authentic samples.22
that aldehydes were not further oxidized to the corresponding car-
boxylic acids (Table II). As shown in Table II, ortho-substituents make
the oxidation of the dithianes slower, and therefore prolonged reaction
times are needed. The presence of a bromine atom or of a methyl group
2
(
R = CH3, Br) leads to an increase of the rate of the final hydrolytic
cleavage.
In conclusion, in this article we have reported the use of TSA 1 as a
novel heterogeneous solid acid in a convenient, efficient, and practical
method for the effective oxidation of thiols and oxidative deprotection
of 1,3-dithianes. The availability of the reagents, easy and clean work-
up, and high yields make this method a useful alternative to literature
methodologies.
EXPERIMENTAL
Thiols and other chemicals were purchased from Merck, Fluka, and
Aldrich. 1,3-dithianes were prepared from the corresponding carbonyl
SCHEME 3

2
830
B. Karami et al.
compounds according to the reported procedure.19 The reactions were
monitored by TLC (silica-gel 60 F254,n-hexane:ethylacetate). Products
were isolated and identified by comparison of their physical and spec-
tral data with those of authentic samples.1
,10,16−17,20−22
IR spectra were
1
recorded on a FTIR JASCO-680 spectrometer and H NMR spectra were
obtained with a Bruker DPX-300 instrument.
The Preparation of Tungstate Sulfuric Acid (1)
To 0.2 mol (23.3 g, 13.3 mL) of chlorosulfonic acid in a 250-mL round-
bottom flask was cooled with an ice bath, and 0.1 mol (29.4 g) of anhy-
drous sodium tungstate was gradually added. After the completion of
the addition, the mixture was shaken for 1 h, 10 mL cooled water was
added, and the mixture was filtered under suction. A yellowish-white
solid (TSA) 40.2 g (98.0%), m.p. 285 (dec.) was obtained. Characteristic
−1
IR bands (KBr, cm ); 3600–2200 (OH, bs), 1240–1140 (S O, bs), 1060
S-O, m), 1005 (S-O, m), 880–840 (W O, m), 450 (W-O, m).
(
The Oxidation of Thiols: General Procedure
To a solution of 2 mmol of the thiol in 8 mL of dichloromethane, 0.5 mmol
wet (10% w/w) TSA (1) and 1 mmol NaNO2 were added. The reaction
mixture was stirred at r.t. when a light-green heterogeneous solution
was obtained rapidly, the color of which then disappeared. The progress
of the reaction was monitored by TLC (n-hexane:ethylacetate). When
the reaction was complete, the reaction mixture was filtered and washed
with 4 mL of dichloromethane. The dichloromethane was removed by
◦
distillation using a water bath (40–50 C). The yields are summarized
in Table I.
The Oxidative Deprotection of 1,3-Dithianes: General
Procedure
To a solution of 1 mmol of the 1,3-dithiane in 4 mL of dichloromethane,
2
mmol KMnO4 and 6 mmol wet (10% w/w) TSA (1) were added. The
reaction mixture was stirred at r.t. when a brownish heterogeneous so-
lution was obtained. The progress of the reaction was monitored by TLC
(
n-hexane:ethylacetate 8:2). When the rection was complete, the reac-
tion mixture was filtered and washed with 4 mL of dichloromethane.
The dichloromethane was removed by distillation using a water bath
◦
(
40–50 C). The yields are summarized in Table II.

Tungstate Sulfuric Acid
2831
REFERENCES
[
[
[
1] M. A. Zolfigol, Tetrahedron, 57, 9509 (2001).
2] G. A. Olah, R. Molhotra, and S. C. Narang, J. Org. Chem., 43, 4628 (1987).
3] M. A. Zolfigol, F. Shirini, A. Ghorbani Choghamarani, and I. Mohammadpoor-
Baltork, Green Chem., 4, 562 (2002).
[
4] M. A. Zolfigol and A. Bamoniri, Synlett., 1621 (2002).
[
5] (a) B. F. Mirjalili, M. A. Zolfigol, and A. Bamoniri, J. Kor. Chem. Soc., 45, 546 (2001);
(
b) B. F. Mirjalili, M. A. Zolfigol, and A. Bamoniri, Molecules, 7, 751 (2002).
6] (a) B. F. Mirjalili, M. A. Zolfigol, A. Bamoniri, and A. Zarei, Bull. Kor. Chem. Soc., 24,
00 (2003); (b) B. F. Mirjalili, M. A. Zolfigol, A. Bamoniri, and Z. Zaghaghi, J. Chem.
[
4
Res. (S), 273 (2003); (c) B. F. Mirjalili, M. A. Zolfigol, A. Bamoniri, Z. Zaghaghi,
and A. Hazar, Acta Chem. Slov., 50, 563 (2003); (d) F. Shirini, M. A. Zolfigol, and
K. Mohammadi, Bull. Kor. Chem. Soc., 25, 325 (2004).
[7] M. A. Harmer and Q. Sun, Appl. Catal. A: General, 221, 45 (2001).
[8] I. Pe’er, C. E. Felder, O. Man, I. Silman, and J. L. Sussman, Proteins, 54, 20 (2004).
[9] J. C. Bardwell, Mol. Microbiol., 14, 199 (1994).
[
10] (a) M. M. Khodaei, I. Mohammadpoor-Baltork, and K. Nikoofar, Bull. Kor. Chem.
Soc., 24, 885 (2003) and references cited therein; (b) A. Khazaei, M. A. Zolfigol, and
A. Rostami, Synthesis, 2959 (2004); (c) G. B. Jensen, G. Smith, D. S. Sagatys, P. C.
Healyb, and J. M. White, Acta Cryst., E60, 2438 (2004).
[
[
11] A. Lebouc, J. Simonet, J. Gelas, and A. Dehbi, Synthesis, 320 (1987).
12] M. H. Habibi, S. Tangestaninejad, M. Montazerozohori, and I. Mohammadpoor-
Baltork, Molecules, 8, 663 (2003) and references cited therein.
[
[
[
13] M. H. Habibi, S. Tangestaninejad, and M. Montazerozohori, Polish J. Chem., 78,
201 (2004).
14] M. H. Habibi, S. Tangestaninejad, M. Montazerozohori, and I. Mohammadpoor-
Baltork, Phosphorus, Sulfur, and Silicon, 179, 597 (2004).
15] (a) A. Heydari, H. Larijani, J. Emami, and B. Karami, Tetrahedron Lett., 41, 2471
(
2000); (b) J. Asgarian Damavandi, M. A. Zolfigol, and B. Karami, Synth. Commun.,
31, 129 (2001).
[16] N. Iranpoor, H. Firouzabadi, and M. A. Zolfigol, Synth. Commun., 28, 367 (1998).
[17] H. Firouzabadi, N. Iranpoor, and M. A. Zolfigol, Synth. Commun., 28, 1179 (1998).
[18] G. W. Gokel, H. M. Gerdes, and D. M. Dishong, J. Org. Chem., 45, 3634 (1980).
[19] (a) H. Firouzabadi, N. Iranpoor, and B. Karimi, Synthesis, 58 (1999); (b) D. Seebach,
and E. J. Corey, J. Org. Chem., 40, 231 (1975); (c) B. T. Groblel and D. Seebach,
Synthesis, 357 (1977); (d) R. P. Hatch, J. Shringarpure, and S. M. Weinreb, J. Org.
Chem., 43, 4172 (1978); (e) J. A. Marshall and J. L. Belletire, Tetrahedron Lett., 871
(
1971); (f) F. A. J. Meskens, Synthesis, 501 (1981).
20] M. A. Zolfigol, D. Nematollahi, and S. E. Mallakpour, Synth. Commun., 29, 2277
1999).
[
(
[
21] M. A. Zolfigol, Synth. Commun., 30, 1593 (2000).
[
22] (a) Dictionary of Organic Compounds, 6th ed., (Chapman and Hall, London, 1982);
(
b) Merck Catalog of Chemicals, 2005–2007.