Dinitrogen tetroxide impregnated charcoal (N2O 4/Charcoal): Selective oxidation of thiols to disulfides or thiosulfonates

Article abstract of DOI:10.1080/10426500500263656

Selective oxidation of thiols to disulfides (RSSR) was performed by using catalytic amounts of dinitrogen tetroxide/charcoal in chloroform at r.t. while the reaction of thiols with four molar equivalents of the reagent in dichloromethane afforded thiosulfonates (RSO₂SR) with excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500500263656

This article was downloaded by: [University of Arizona]
On: 31 December 2012, At: 12:43
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Dinitrogen Tetroxide
Impregnated Charcoal (N O /
2
4
Charcoal): Selective Oxidation
of Thiols to Disulfides or
Thiosulfonates
a
a
Nasser Iranpoor , Habib Firouzabadi & Ali Reza
a
Pourali
a
Department of Chemistry, Shiraz University, Shiraz,
Iran
Version of record first published: 01 Feb 2007.
To cite this article: Nasser Iranpoor , Habib Firouzabadi & Ali Reza Pourali (2006):
Dinitrogen Tetroxide Impregnated Charcoal (N O /Charcoal): Selective Oxidation of
2
4
Thiols to Disulfides or Thiosulfonates, Phosphorus, Sulfur, and Silicon and the Related
Elements, 181:3, 473-479
To link to this article: http://dx.doi.org/10.1080/10426500500263656
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.

The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

Phosphorus, Sulfur, and Silicon, 181:473–479, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500263656
Dinitrogen Tetroxide Impregnated Charcoal
(
N O /Charcoal): Selective Oxidation of Thiols
2 4
to Disulfides or Thiosulfonates
Nasser Iranpoor
Habib Firouzabadi
Ali Reza Pourali
Department of Chemistry, Shiraz University, Shiraz, Iran
Selective oxidation of thiols to disulfides (RSSR) was performed by using catalytic
amounts of dinitrogen tetroxide/charcoal in chloroform at r.t. while the reaction
of thiols with four molar equivalents of the reagent in dichloromethane afforded
thiosulfonates (RSO SR) with excellent yields.
2
Keywords Dinitrogen tetroxide; disulfides; oxidation; thiols; thiosulfonates
INTRODUCTION
Disulfides are of great importance in chemistry as well as in
1
biochemistry. Sulfur–sulfur bonds between cysteine residues stabilize
three-dimensional structures of many peptides. Furthermore, organic
compounds possessing disulfide and thiosulfonate functional groups are
synthetically useful sulfenylating agents.2
The oxidation of thiols is the most exploited method for disulfide syn-
thesis, mainly because a large number of thiols are commercially avail-
able and/or are easily synthesized. The selective oxidative coupling of
thiols to disulfides is of interest from a synthetic perspective. Thiols
are among functional groups, which can be easily over oxidized and,
therefore, extensive methods have been reported for their controlled
oxidation. Most of the existing methods involve the use of a stoichio-
3
4
metric amount of oxidants, such as oxo and peroxosalts, halogens,
metal oxidants,5 bis-tetra-n-buthylammonium thiosulfate, dichloro-
dioxo molybdenum(VI)/dimethy sulfoxide, diazenecarboxamides,
6
7
8
Received January 17, 2005; accepted October 4, 2005.
The authors are thankful to the Shiraz University Research Council for their partial
support of this work.
Address correspondence to Nasser Iranpoor, Shiraz University, Department of Chem-
istry, College of Sciences, Shiraz 71454, Iran. E-mail: iranpoor@chem.susc.ac.ir
473

4
74
N. Iranpoor et al.
9
10
clay-supported ferric nitrate, silica sulfuric acid/sodium nitrite, and
1
1
peroxynitrite. The catalytic oxidative coupling of thiols to disul-
fides in the presence of air or oxygen has great industrial im-
portance in the purification of hydrocarbon raw materials to re-
move sulfur compounds, impairing the quality of motor fuels and
poisoning catalysts in various stages of manufacturing synthetic
1
2
rubber. Some catalysts have been introduced for the oxidative
coupling of thiols in the presence of oxygen or air, such as cop-
per(I) dimercapto complexes,12 iron(III)/sodium iodide,
13a
trifluroac-
etato titanium(IV) trichloride and bis-trifluroacetato titanium(IV) ox-
ide/sodium iodide1 basic alumina,
3b
14a
cesium fluoride/Celite,
14b
metal
copper nitrate dintrogen
tetroxide hydrated copper nitrate, and tetrabutylammonium peri-
14c
salts of 4-aminobenzoic acid/silica gel,
1
5a
15b
16
odate/aluminum chloride. Many of these methods suffer from long re-
action times, undesirable side reactions, laborious isolation procedures,
difficult preparation, or unavailability due to their reagents.
RESULTS AND DISCUSSION
Gaseous dinitrogen tetroxide has been reported to catalyze the forma-
tion of disulfides from thiols via S-nitrosothiols and an autocatalytic
mechanism has been suggested for the decomposition of S-nitrosothiols
in aerated solutions.17
Apart from difficulties in handling and the poisonous and corrosive
nature of dinitrogen tetroxide, a further serious disadvantage of using
dinitrogen tetroxide in organic synthesis is its high reactivity. In order
to decrease its reactivity and avoid the formation of side products, low
temperatures (that are strictly controlled) are always employed.18
In continuation of our program on the preparation and use of safe
and solid supported forms of dinitrogen tetroxide in organic synthesis,19
we recently reported dinitrogen tetroxide impregnated charcoal as a
cheap, stable, and easily prepared reagent for the heterogeneous ox-
idation of sulfides, disulfides, benzylic alcohols, ethers, and nitrosa-
2
0
tion reactions. By introducing dinitrogen tetroxide to a suspension
of activated charcoal in dichloromethane, dinitrogen tetroxide/charcoal
was obtained with a high capacity of dinitrogen tetroxide. In compari-
son to solid complexes of dinitrogen tetroxide that we have previously
1
9a−e
reported,
this reagent has higher capacity. In addition to the cheap-
ness and availability of charcoal for the preparation of this reagent, af-
ter completion of the reaction, no organic residue is produced from the
reagent, which provides an easy work up. Dinitrogen tetroxide/charcoal
is very stable in a refrigerator without loosing its activity for months.

Dinitrogen Tetroxide Impregnated Charcoal
475
TABLE I Catalytic Oxidative Coupling of Thiols (1.0 mmol) with
Dinitrogen Tetroxide/Charcoal (0.2 mmol) in CHCl
temperature
3
at room
Time
(min.)
Isolated
yield %
Entry
Thiol
Producta
1
2
3
4
5
6
7
n-C4H9SH
sec-C4H9SH
n-C5H11SH
n-C8H17SH
C6H5SH
(n-C4H9S)2
(sec-C4H9S)2
(n-C5H11S)2
(n-C8H17S)2
(C6H5S)2
90
120
80
100
120
140
60
90
80
92
85
80
90
96
C6H5-CH2SH
(C6H5-CH2S)2
8
9
80
82
80
220
aThe products were characterized by their comparison with known compounds.19f
Now, we report the new applications of dinitrogen tetroxide/charcoal
as a selective and efficient catalyst for the oxidative coupling of thiols
to disulfides and/or as a selective reagent for the conversion of thiols
to thiosulfonates. The catalytic coupling of thiols was performed with
0.2 molar equivalents of dinitrogen tetroxide/charcoal in the presence
of oxygen in chloroform at room temperature (see Scheme 1, Table I).
N2O4/Charcoal
(
0.2 mmol)
RSH −−−−−−−→ RSSR
O2, r.t., CHCl3
SCHEME 1
The use of this reagent provides the possibility of the catalytic oxida-
tive coupling of thiols under mild and heterogeneous conditions. The
produced disulfides are isolated with excellent purity and high yields.
Thiosulfonates (sulfonic S-esters) have shown valuable biological
2
1a,b
activities.
plication both in polymer production and in photographic processes.
They have been reported to be strong sulfenylating agents, which re-
Furthermore, thiosulfonates have a wide industrial ap-
2
1c,d
22
act even faster than disulfides and are extensively utilized in organic
syntheses for sulfide and disulfide formation or aromatic thiocyanation

4
76
N. Iranpoor et al.
with the thiolate anion.2,23 However, the use of thiosulfonates has been
limited by the lack of easy and practical preparations. Only a few routes
are reported in the literature for their preparation from thiols.18a,24
The synthesis of thiosulfonates from thiols with excess dinitrogen
◦
18a
tetroxide at low temperatures (−20 C),
[bis(trifluoroacetoxy)iodo]
2
4a
24b
benzene,
and sulfonyl chloride
have been reported. The two first
methods suffer from over oxidation of thiosulfonates into sulfonic acids
as byproducts and good yields were obtained only when aromatic thi-
ols were used. With the latter method, reaction of sulfonyl chlorides
with heterocyclic aromatic thiols gives unsymmetrical thiosulfonates
with moderate yields. Very recently we also reported on the use of
tetrabutylammonium peroxymonosulfate/imidazole/manganese meso-
tetraphenylporphyrin for this conversion.2
4d
The use of dinitrogen tetroxide/charcoal provides a suitable route
for the direct preparation of thiosulfonates from thiols under mild and
heterogeneous conditions with high yields. The workup of the reaction
is very easy and thiosulfonates are isolated with excellent purity.
The one-pot conversion of thiols to thiosulfonates was achieved suc-
cessfully in dichloromethane at r.t. using four molar equivalents of ni-
trogen tetroxide/charcoal (Scheme 2, Table II).
N2O4/Charcoal
(
4 mmol)
RSH −−−−−−−→ RSO2SR
r.t., CH2Cl2
SCHEME 2
The conversion of thiols to thiosulfonates occurs through the inter-
mediacy of disulfide. This was demonstrated by analyzing the prod-
uct mixture obtained from the reaction of thiophenol with an excess of
dinitrogen tetroxide after 10 min. The analysis showed that a mixture
of diphenyl disulfide and the corresponding thiosulfonate is obtained.
In addition, the reaction of diphenyl disulfide with excess dinitrogen
tetroxide produces the corresponding thiosulfonate.
In conclusion, dinitrogen tetroxide/activated charcoal as a safe,
cheap, and easily available solid source of dinitrogen tetroxide acts as
a stable oxidizing agent for sulfur compounds. The high efficiency and
excellent selectivity of this reagent for the heterogeneous and selec-
tive oxidation of thiols to disulfides or thiosulfonates are considered as
strong advantages of this method.

Dinitrogen Tetroxide Impregnated Charcoal
477
TABLE II Oxidation of Thiols to Thiosulfonates with
Dinitrogen Tetroxide/Charcoal at room temperature
Time
(min.)
Isolated
yield %
Entry
Thiol
Producta
1
2
3
n-C4H9SH
n-C8H17SH
C6H5SH
n-C4H9SO2SC4H9
n-C8H17SO2SC8H17
C6H5SO2SC6H5
30
45
60
95
90
98
4
5
60
50
88
96
4-CH3C6H5SH
3-CH3C6H5SH
6
65
95
a
The products were characterized by their comparison with known
1
9f
compounds.
EXPERIMENTAL
General
Chemicals were purchased from Merck and Fluka Chemical Compa-
nies. The products were characterized by comparison of their spectral
data with those of known samples. IR spectra were run on a Shimadzu
model 8300 FT-IR spectrophotometer. NMR spectra were recorded on a
Bruker Avance DPX-250. Mass spectra were recorded on a Shimadzu
GCMS-QP 1000 EX. The purity of the products and the progress of the
reactions were accomplished by TLC on silica-gel polygram SILG/UV254
plates or by a Shimadzu Gas Chromatograph GC-14A instrument with
a flame ionization detector.
Catalytic Oxidative Coupling of Thiophenol
to Diphenyl Disulfide
To a stirred solution of thiophenol (0.11 g, 1 mmol) in pre-oxygenated
CHCl3(5 mL), catalytic amounts of N2O4/charcoal (0.05 g, 0.2 mmol)
were added under an atmosphere of O2 at r.t. The reaction mixture was
stirred for 2 h and then was filtered. Evaporation of the solvent followed
by purification of the product by chromatography on a short column

4
78
N. Iranpoor et al.
of silica gel eluted with n-hexane, which afforded diphenyl disulfide
◦
25
◦
(
0.087 g, 80%), m.p. 61–63 C; (Lit., m.p. 61–62 C).
Oxidation of 4-Methyl Thiophenol to S-(4-Methylphenyl)
-Methylbenzene Thiosulfonate
4
To the solution of 4-methyl thiophenol (0.124 g, 1 mmol) in CH2Cl2
5 mL), the reagent (0.88 g, 4 mmol) was added with stirring at r.t.
(
After 50 min., the reaction mixture was filtered. Evaporation of the
solvent followed by chromatography on a short column of silica gel
eluted with n-hexane/EtOAc (5:1), which gave S-(4-methylphenyl) 4-
◦
22
methylbenzenethiosulfonate (0.134 g, 96%); m.p. 74–75 C (Lit. m.p.
◦
73–75 C).
REFERENCES
[
1] (a) R. J. Cremlyn, An Introduction to Organosulfur Chemistry (John-Wiley & Sons,
New York, 1996); (b) S. Oae, Organic Sulfur Chemistry: Structure and Mechanism
(
CRC: Boca Raton, FL, 1991); (c) B. Gaston, Biochim. Biophys. Acta, 1411, 323
(
1999).
[
[
2] B. M. Trost, Chem. Rev., 78, 363 (1978); (b) L. H. Fallois, J.-L. De’cout, and
M. Fontecave, J. Chem. Soc., Perkin Trans. 1, 2587 (1997).
3] (a) A. R. Hajipour, S. E. Mallakpour, and H. Adibi, J. Org. Chem. 67, 8666 (2002);
(
1
b) V. Kesavan, D. Bonnet-Delpon, and J. P. Begue, Synthetic Communication, 35,
517 (2005); (c) A. McKillop and D. Kuyuncu, A. Krief, W. Dumout, P. Reuiev, and
M. Trabels, Tetrahedron Lett., 31, 5007 (1990); (d) M. C. Noureldin, J. Hendry, and
D. G. Lee, Synthesis, 1587 (1998).
[
[
4] (a) M. H. Ali and M. McDermott, Tetrahedron Lett., 43, 6271 (2002); (b) X. Wu and
R. D. Rieke, Synthetic Commun., 26, 191 (1996); (c) J. Drabwicz and M. Mikolajczyk,
Synthesis, 32 (1980).
5] (a) T. J. Wallace, J. Org. Chem., 31, 1217 (1966); (b) H. Firouzabadi, N. Iranpoor,
and H. A. Parham, Synthetic Commun., 14, 717 (1984); (c) H. Firouzabadi, M.
Naderi, A. Sardarian, and M. Vessal, Synthetic Commun., 13, 611 (1983); (d) M.
Tajbakhsh, I. Mohammadpoor-Baltork, and K. Alimohammadi, Monatsh. Chem.,
134, 1571 (2003); (e) M. M. Khodaei, I. Mohammadpoor-Baltork, and K. Nikoofar,
Bull. Korean Chem. Soc., 24, 885 (2003); (f) M. Tajbakhsh, R. Hosseinzadeh, and A.
Shakoori, Tetrahedron Lett., 45, 1889 (2004).
[
6] F.-E. Chen, Y.-W. Lu, Y.-P. He, Y.-F. Luo, and M.-G. Yan, Synthetic Commun., 32,
3487 (2002).
[7] R. Sanz, R. Aguado, M. R. Pedrosa, and F. J. Arna’iz, Synthesis, 856 (2002).
[8] J. Kosmrlj, M. Kocevar, and S. Polanc, J. Chem. Soc., Perkin Trans. 1, 3917 (1998).
[9] A. Cornelis, N. Depaye, A. Gerstmans, and P. Laszlo, Tetrahedron Lett., 24, 3103
(
1983).
[
[
[
10] M. A. Zolfigol, Tetrahedron, 57, 9509 (2001).
11] L. Grossi, P. C. Montevecchi, and S. Strazzari, Eur. J. Org. Chem., 131 (2001).
12] G. A. Bagiyan, I. K. Koroleva, N. V. Soroka, and A. V. Ufimtsev, Russ. J. Appl. Chem.,
76, 88 (2003).

Dinitrogen Tetroxide Impregnated Charcoal
479
[
[
13] (a) N. Iranpoor and B. Zeynizadeh, Synthesis, 49 (1999); (b) B. Zeynizadeh and
N. Iranpoor, J. Chin. Chem. Soc., 50, 849 (2003).
14] (a) K.-T. Liu and Y.-C. Tong, Synthesis, 669 (1978); and references therein, (b) S. T. A.
Shah, K. M. Khan, M. Fecker and W. Voelter, Tetrahedron Lett., 44, 6789 (2003);
(
c) M. M. Hashemi and Z. Karimi-Jaberi, Monatsh. Chem., 135, 41 (2004).
15] (a) N. Iranpoor, H. Firouzabadi, and M. A. Zolfigol, Synthetic Commun., 28, 367
1998); (b) N. Iranpoor, H. Firouzabadi, and M. A. Zolfigol, Synthetic Commun., 28,
179 (1998).
16] H. Firouzabadi, A. Sardarian, and H. Badparva, Bull. Chem. Soc. Jpn., 69, 685
1996).
17] (a) L. Grossi, P. C. Montevecchi, and S. Strazzari, J. Am. Chem. Soc., 123, 4853
2001); (b) W. A. Pryor, D. F. Church, C. K. Govindan, and G. Crank, J. Org. Chem.,
7, 159 (1982).
18] (a) Y. H. Kim, K. Shinhama, D. Fukushima, and S. Oae, Tetrahedron Lett., 19, 1211
1978); (b) E. Bosch and J. K. Kochi, J. Org. Chem., 60, 3172 (1995).
[
(
1
[
[
(
(
4
[
[
(
19] (a) N. Iranpoor, H. Firouzabadi, and R. Heydari, J. Chem. Res. (S), 668 (1999); (b) H.
Firouzabadi, N. Iranpoor, and R. Heydari, Phosphorus, Sulfur, Silicon, Relat. Elem.,
1
3
77, 631 (2002); (c) H. Firouzabadi, N. Iranpoor, and R. Heydari, Synthetic Commun.,
1, 2037 (2001); (d) H. Firouzabadi, N. Iranpoor, and R. Heydari, Synthetic Com-
mun., 33, 703 (2003); (e) N. Iranpoor, H. Firouzabadi, and R. Heydari, Phosphorus,
Sulfur, Silicon, Relat. Elem., 178, 1027 (2003); (f) N. Iranpoor, H. Firouzabadi, and
A. R. Pourali, Tetrahedron, 58, 5179 (2002); (g) N. Iranpoor, H. Firouzabadi, and
A. R. Pourali, Synthesis, 1591 (2003).
[
20] (a) N. Iranpoor, H. Firouzabadi, and A. R. Pourali, Synlett., 347 (2004); (b) N. Iran-
poor, H. Firouzabadi, and A. R. Pourali, Synthetic Commun., in press.
21] (a) J. P. Weidner and S. S. Block, J. Med. Chem., 7, 671 (1964); (b) S. S. Block and
J. P. Weidner, Mech. React. Sulfur Compd., 2, 235 (1968); (c) N. S. Zefirof, N. V. Zyk,
E. K. Beloglazkina, and A. G. Kutateladze, Sulfur Reports, 14, 223 (1993); (d) K.
Fujiki, S. H. Akieda, Yasuda, and Y. Sasaki, Synthesis, 1035 (2001).
[
[
22] G. Palumbo and R. Caputo, Synthesis, 888 (1981).
[
23] (a) T. F. Parsons, J. D. Buckman, D.E. Pearson, and L. Field, J. Org. Chem., 30, 1923
(
1965); (b) K. Fujiki, S. Akieda, H. Yasuda, and Y. Sasaki, Synthesis, 1035 (2001);
(
c) K. Fujiki and E. Yoshida, Synthetic Commun., 29, 3289 (1999); (d) G. Palumbo,
C. Ferreri, C. D’Ambrocio, and R. Caputo, Phosphorus, Sulfur, Silicon, Relat. Elem.,
9, 235 (1984) and references cited therein.
1
[
24] (a) M. Xia and Z.-C. Chen, Synthetic Commun., 27, 1301 (1997); (b) J.-P. Mahieu,
M. Gosselet, B. Sebille, and Y. Beuzard, Synthetic Commun., 16, 1709 (1986); (c) N.
Iranpoor, D. Mohajer, and A. R. Rezaeifard, Tetrahedron Lett. 45, 3811 (2004).
25] D. R. Lide, CRC Handbook of Chemistry and Physics, 80th ed, (CRC Press: Boca
Raton, FL, 1999).
[