Silica sulfuric acid/NaNO2 as a novel heterogeneous system for production of thionitrites and disulfides under mild conditions

Article abstract of DOI:10.1016/S0040-4020(01)00960-7

Neat chlorosulfonic acid reacts with silica gel to give silica sulfuric acid in which sulfuric acid is immobilized on the surface of silica gel via covalent bond. Thiols can be readily converted to their corresponding thionitrites with a combination of silica sulfuric acid, wet SiO₂ and sodium nitrite in dichloromethane at room temperature. Disulfides result from the homolytic cleavage of the sulfur-nitrogen bond of the unstable thionitrites and subsequent coupling of the resultant thiyl radicals.

Full text of DOI:10.1016/S0040-4020(01)00960-7

TETRAHEDRON
Pergamon
Tetrahedron 57 ꢀ2001) 9509±9511
Silica sulfuric acid/NaNO as a novel heterogeneous system for
2
production of thionitrites and disul®des under mild conditions
p
Mohammad Ali Zol®gol
Department of Chemistry, College of Science, Bu-Ali Sina University, P.O. Box 4135, Hamadan 65174, Iran
Received 9 April 2001; revised 23 August 2001; accepted 13 September 2001
AbstractÐNeat chlorosulfonic acid reacts with silica gel to give silica sulfuric acid in which sulfuric acid is immobilized on the surface of
silica gel via covalent bond. Thiols can be readily converted to their corresponding thionitrites with a combination ofsilica sul fu ric acid, wet
2
SiO and sodium nitrite in dichloromethane at room temperature. Disul®des result from the homolytic cleavage of the sulfur±nitrogen bond
ofthe unstable thionitrites and subsequent coupling ofthe resultant thiyl radicals. q 2001 Elsevier Science Ltd. All rights reserved.
4
,5
Any reduction in the amount ofsul fu ric acid needed and/or
any simpli®cation in handling procedures is required for
risk reduction, economic advantage and environment
thiols, since ꢀa) they are being examined as possible
drugs to effect vasodilatation and to reduce platelet aggre-
gation, ꢀb) they are now believed to play an important part in
1
5
protection. In addition, there is current research and general
some ofthe physiological processes involving nitric oxide
and ꢀc) they are being investigated as a source ofthiyl
interest in heterogeneous systems because ofthe importance
such systems have in industry and in developing tech-
nologies. In continuation ofour studies on the application
6
radicals or as nitrosating agents.
7
2
ofinorganic acidic salts we fo und that silica gel reacts with
chlorosulfonic acid to give silica sulfuric acid ꢀI). It is
interesting to note that the reaction is easy and clean without
any work-up procedure because HCl gas is evolved from the
reaction vessel immediately ꢀScheme 1).
The most general nitrosating reagent is nitrous acid,
generated from sodium nitrite and mineral acid in water or
in mixed alcohol±water solvents. Other nitrosating agents
have been used successfully to synthesize thionitrites,
notably alkyl nitrites, nitrosyl salts, dinitrogen trioxide,
4
8
dinitrogen tetroxide, oxalic acid dihydrate or inorganic
acidic salts and sodium nitrite. Very recently, we among
9
We hoped that the silica sulfuric acid ꢀI) would be a superior
proton source to all ofthe reported acidic solid supports
or acidic resins such as polystyrene sulfonic acid and
many others, have demonstrated that heterogeneous reagent
systems have many advantages such as simple experimental
procedures, mild reaction conditions and minimization of
chemical wastes as compared to the liquid phase counter-
3
Na®on-H for running reactions under heterogeneous con-
ditions. Therefore, we were interested in using this
inorganic acidic resin ꢀI) for the in situ generation of
HNO when used in conjunction with NaNO , wet SiO
1
0
parts. Therefore, we decided to apply silica sulfuric acid
ꢀI)/NaNO as a new heterogeneous system for the nitro-
2
2
2
2
and an organic solvent. On the other hand, thionitrites
have not been as widely studied as their oxygen counterparts
alkyl nitrites, generally because oftheir reduced stability.
However, in recent years there has been much interest
generated in the chemistry and biochemistry ofnitroso-
sation ofthiols. We wish to report a simple, cheap and
convenient method for the effective nitrosation of thiols
and production ofdisul®des under mild and heterogeneous
conditions ꢀScheme 2).
4
Different kinds of thiols were subjected to the nitrosation
reaction in the presence ofNaNO , wet SiO ꢀ50% w/w) and
2
2
silica sulfuric acid ꢀI) in dichloromethane. The nitrosation
reactions were performed under mild and completely
heterogeneous conditions. A bright-red heterogeneous
solution was obtained immediately due to the formation of
thionitrite. Disul®des result from the homolytic cleavage of
the sulfur±nitrogen bond of the unstable thionitrite and
Scheme 1.
1
1,12
subsequent coupling ofthe resultant thiyl radicals.
Therefore, this method could be used for conversion of
thiols to their corresponding disul®des quantitatively with
increasing temperature ꢀScheme 2 and Table 1).
Keywords: silica sulfuric acid; thiols; thionitrites; disul®des.
Tel.: 198-811-8271075; fax: 198-811-8272404;
e-mail: zol®@basu.ac.ir
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020ꢀ01)00960-7

9510
M. A. Zol®gol / Tetrahedron 57 ꢀ2001) 9509±9511
Scheme 2.
Table 1. Nitrosation ofthiols to their corresponding unstable nitrosothiols ꢀ 2) and production ofdisul®des ꢀ 3) with a combination ofsilica sul fu ric acid ꢀ I),
2 2
NaNO ꢀII) and wet SiO ꢀ50% w/w) in dichloromethane at room temperature
a
Yields ꢀ%)
Entry
Substrate
Product
Time ꢀmin)
Mp ꢀ8C)
Found
Reported
1
4
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
3a
3b
3c
3d
3e
3f
2
1.5
1.5
3
2
5
0.75
1
3
97
98
95
99
97
98
95
94±68
Oil
Oil
Oil
135±137
25
56±58
±
42±45
69±70
17
138
24±24.5
14
11±17
3g
b
59±60
45±47
b
±
±
98
17
3i
a
Isolated yields.
Polymerization occurred.
b
Although the reaction occurs without wet SiO the reaction
2
dehaen AG and Aldrich chemical companies. Disul®des
,
1
time period is very long and complete only after several
days. Therefore we think that the presence of wet SiO2
acts as a media and provides a heterogeneous effective
were characterized by comparison oftheir spectral ꢀIR,
NMR, and TLC) and physical data with the authentic
H
8
,9,11±17
samples.
surface area for in situ generation of HNO . Nitrosation
2
did not occur in the absence ofsilica sul fu ric acid ꢀ I).
1.2. Preparation of silica sulfuric acid
In conclusion, silica sulfuric acid ꢀI) is a good proton source
in terms ofconvenience, cheapness, easy production,
insolubility to all organic solvents. Practical and ef®cient
nitrosation±oxidation ofthiols were achieved by the present
methodology. The cheapness and availability ofthe
reagents, easy procedure and work-up make this method
attractive for the large-scale operations.
A 500 mL suction ¯ask was used. It was equipped with a
constant-pressure dropping funnel containing chlorosul-
fonic acid ꢀ23.3 g, 0.2 mol) and gas inlet tube for conducting
HCl gas over an adsorbing solution i.e. water. Into it were
charged 60.0 g ofsilica gel. Chlorosul fo nic acid was added
dropwise over a period of30 min at room temperature. HCl
gas evolved from the reaction vessel immediately ꢀScheme
1). After the addition was complete the mixture was shaken
for 30 min. A white solid ꢀsilica sulfuric acid) of 76.0 g was
obtained.
1. Experimental
1
.1. General
1.3. Typical experimental procedure
Chemicals were purchased from Fluka, Merck, Riedel-
To a solution ofthiophenol ꢀ0.220 g, 2 mmol) in CH Cl
2
2

M. A. Zol®gol / Tetrahedron 57 ꢀ2001) 9509±9511
10 mL), I ꢀ1.520 g, 4 mmol), wet SiO ꢀ50% w/w) ꢀ0.4 g)
9. Zol®gol, M. A. Synth. Commun. 2000, 30, 1593.
2
9511
ꢀ
and NaNO ꢀ0.257 g, 4 mmol) were added. The resulting
2
10. ꢀa) Zol®gol, M. A.; Kiany-Borazjani, M.; Sadeghi, M. M.;
Mohammadpoor-Baltork, I.; Memarian, H. R. Synth.
Commun. 2000, 30, 551. ꢀb) Zol®gol, M. A.; Kiany-Borazjani,
M.; Sadeghi, M. M.; Memarian, H. R.; Mohammadpoor-
Baltork, I. Synth. Commun. 2000, 30, 2945. ꢀc) Zol®gol,
M. A.; Kiany-Borazjani, M.; Sadeghi, M. M.; Memarian,
H. R.; Mohammadpoor-Baltork, I. J. Chem. Res. ꢀS) 2000,
197. ꢀd) Zol®gol, M. A.; Mallakpour, S. E. Synth. Commun.
1999, 29, 4061. ꢀe) Zol®gol, M. A.; Kiany-Borazjani, M.;
Mallackpour, S. E.; Nassr-Isfahani, H. Synth. Commun.
2000, 30, 2573. ꢀf) Zol®gol, M. A.; Madrakian, E.; Ghaemi,
E. Indian J. Chem. 2000, 39B, 308. ꢀg) Zol®gol, M. A.;
Mallakpour, S. E.; Ghaemi, E.; Madrakian, E. Synth.
Commun. 2000, 30, 1689. ꢀh) Zol®gol, M. A.; Kiany-
Borazjani, M.; Sadeghi, M. M.; Mohammadpoor-Baltork, I.;
Memarian, H. R. Synth. Commun. 2000, 30, 3919. ꢀi) Zol®gol,
M. A. Synth. Commun. 1999, 29, 905. ꢀj) Zol®gol, M. A.;
Ghaemi, E.; Madrakian, E.; Kiany-Borazjani, M. Synth.
Commun. 2000, 30, 2057. ꢀk) Zol®gol, M. A.; Shirini, F.;
Ghorbani Choghamarani, A.; Taqian-nasab, A.; Keypour,
H.; Salehzadeh, S. J. Chem. Res. ꢀS) 2000, 420. ꢀl) Zol®gol,
M. A.; Ghorbani Choghamarani, A.; Shirini, F.; Keypour, H.;
Salehzadeh, S. Synth. Commun. 2001, 31, 359. ꢀm) Zol®gol,
M. A.; Zebarjadian, M. H.; Chehardoli, G.; Mallakpor, S. E.;
Shamsipur, M. Tetrahedron 2001, 57, 1627. ꢀn) Zol®gol,
M. A.; Ghaemi, E.; Madrakian, E. Molecules 2001, 6, 614.
mixture was stirred at room temperature and a bright red
heterogeneous solution was obtained immediately. Thio-
nitrites were characterized by comparison oftheir UV
1
1,12
spectra with those reported in the literature.
spectra are as follows: lmax ꢀCH Cl ): PhSNO, 380, 529,
Typical
2
2
5
3
70 nm]. A pale yellow solution was also obtained after
0 min and then ®ltered. The residue was washed with
CH Cl ꢀ2£10 mL). Anhydrous Na SO ꢀ3 g) was added
2
2
2
4
to the ®ltrate. After 15 min, the resulting mixture was
ltered again. Dichloromethane was removed by water
bath ꢀ40±508C) and simple distillation. The yield was
®
0
5
.210 g ꢀ95%) ofcrystalline brownish solid ꢀ 3g), mp 56±
88C [Lit.
1
1±17
mp 58±608C].
Acknowledgements
Partial support ofthis work by the Bu-Ali Sina University,
Hamadan, Iran is acknowledged.
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