Silica phosphoric acid/NaNO2 as a novel heterogeneous system for the coupling of thiols to their corresponding disulfides

Article abstract of DOI:10.1080/10426500490474842

Silica phosphoric acid was prepared via reaction of silica chloride (I) and phosphoric acid. Thiols can be readily converted to their corresponding thionitrites with a combination of silica phosphoric acid (II), wet SiO ₂, and sodium nitrite in dichloromethane at room temperature. Disulfides result from the homolytic cleavage of the sulfur-nitrogen bond of the unstable thionitrite and subsequent coupling of the resultant thiyl radicals.

Full text of DOI:10.1080/10426500490474842

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SILICA PHOSPHORIC
ACID/NaNO2 AS A NOVEL
HETEROGENEOUS SYSTEM FOR
THE COUPLING OF THIOLS
TO THEIR CORRESPONDING
DISULFIDES
Mohammad Ali Zolfigol a , Farhad Shirini b , Khosrow
Zamani c , Efat Ghofrani a & Satar Ebrahimi c
a Chemistry Department, College of Science, Bu-Ali
Sina University, Hamadan, Iran
b Chemistry Department, College of Science, Gilan
University, Rasht, Iran
c Chemistry Department, College of Science, Arak
University, Arak, Iran
Version of record first published: 16 Aug 2010.
To cite this article: Mohammad Ali Zolfigol, Farhad Shirini, Khosrow Zamani, Efat
Ghofrani & Satar Ebrahimi (2004): SILICA PHOSPHORIC ACID/NaNO2 AS A NOVEL
HETEROGENEOUS SYSTEM FOR THE COUPLING OF THIOLS TO THEIR CORRESPONDING
DISULFIDES, Phosphorus, Sulfur, and Silicon and the Related Elements, 179:11,
2177-2182
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Phosphorus, Sulfur, and Silicon, 179:2177–2182, 2004
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490474842
SILICA PHOSPHORIC ACID/NaNO2 AS A
NOVEL HETEROGENEOUS SYSTEM FOR THE
COUPLING OF THIOLS TO THEIR
CORRESPONDING DISULFIDES
Mohammad Ali Zolfigol,a Farhad Shirini,b Khosrow Zamani,c
Efat Ghofrani,a and Satar Ebrahimic
Chemistry Department, College of Science, Bu-Ali Sina
University, Hamadan, Iran;a Chemistry Department, College
of Science, Gilan University, Rasht, Iran;b and Chemistry
Department, College of Science, Arak University, Arak, Iranc
(Received March 16, 2003; accepted March 18, 2004)
Silica phosphoric acid was prepared via reaction of silica chloride
(I) and phosphoric acid. Thiols can be readily converted to their cor-
responding thionitrites with a combination of silica phosphoric acid
(II), wet SiO2, and sodium nitrite in dichloromethane at room tem-
perature. Disulfides result from the homolytic cleavage of the sulfur–
nitrogen bond of the unstable thionitrite and subsequent coupling of
the resultant thiyl radicals.
Keywords: Disulfides; silica chloride; silica phosphoric acid; thiols;
thionitrites (S-nitrosothiols)
Acids are widely used as catalysts in industry, producing more than
1 × 108 mt/year of products. The most commonly used acids are HF,
H2SO4, HClO4, and H3PO4 (in liquid form or supported on Kieselguhr).
Solid acids have many advantages such as simplicity in handling, de-
creased reactor and plant corrosion problems, and environmentally safe
disposal. There is much current research on and general interest in
heterogeneous systems because of the importance such systems have
in industry and in developing technologies.1,2 In continuation of our
studies on the application of silica resin with acid functional moieties3
Financial support for this work from the Research Council of Bu-Ali Sina University,
Hamadan, Iran is gratefully acknowledged.
Address correspondence to Mohammad Ali Zolfigol, Chemistry Department, Col-
lege of Science, Bu-Ali Sina University, P.O. Box 4135, Hamadan 65174, Iran. E-mail:
zolfi@basu.ac.ir
2177

2178
M. A. Zolfigol et al.
we found that silica chloride (I) is an excellent source for generation of
HCl.4–6 It is interesting to note that the addition of H3PO4 to the silica
chloride gives silica phosphoric acid (II), and HCl was evolved simulta-
neously (Scheme 1). Here we wish to report the first example of silica
solid acid with phosphoric acid moiety.
SCHEME 1
We were also interested in using reagent (II) for the nitrosation of thi-
ols via in situ generation of HNO2 and NO+, respectively, when used in
conjunction with NaNO2 and wet SiO2 in an organic solvent (Scheme 1).
On the other hand, thionitrites have not been as widely studied as
their oxygen counterparts alkyl nitrites, generally because of their re-
duced stability.7 However, in recent years there has been much interest
generated in the chemistry and biochemistry of nitrosothiols,7–14 since
(1) they are being examined as possible drugs to effect vasodilatation
and to reduce platelet aggregation, (2) they are now believed to play an
important part in some of the physiological processes involving nitric
oxide, and (3) they are being used as a source of thiyl radicals7 or as
nitrosating agents. The vital role of thiols and disulfides in living sys-
tems has focused on their interconversion reactions. Intense interest in
the chemistry of thionitrites has been generated in connection with the
newly discovered remarkable physiological roles of nitric oxide, par-
ticularly including vasodilation and cytotoxic action of macrophages.
Thiols and thionitrites (S-nitrosothiols) are believed to be involved in
processes in vivo, possibly in the mechanism of NO transfer reactions.11
The most general reagent is nitrous acid, generated from sodium
nitrite and mineral acid in water or in mixed alcohol–water sol-
vents. Other nitrosating agents have been used successfully to syn-
thesize thionitrites, notably alkyl nitrites, nitrosyl salts, dinitrogen
trioxide, dinitrogen tetroxide,7–10 trichloronitromethane,11 oxalic acid
dihydrate,12 inorganic acidic salts13 or silica sulfuric acid,14 and sodium
nitrite. Very recently we, among many others, demonstrated that het-
erogeneous reagent systems have many advantages such as simple
experimental procedures, mild reaction conditions, and minimization
of chemical wastes as compared to the liquid-phase counterparts.13–16
Therefore, we decided to apply silica phosphoric acid (II)/NaNO2 as a
new heterogeneous system for the oxidation of thiols. We wish to report

Disulfides
2179
a simple, cheap, and convenient method for the effective coupling of
thiols and production of disulfides under mild and heterogeneous con-
ditions (Scheme 2).
SCHEME 2
Different kinds of thiols were subjected to the coupling reaction in
the presence of NaNO2, wet SiO2 (50% w/w), and silica phosphoric acid
(II) in dichloromethane. The coupling reactions were performed under
mild and completely heterogeneous conditions at room temperature. A
bright-red heterogeneous solution was obtained immediately due to the
formation of thionitrite. Disulfides result from the homolytic cleavage
of the sulfur–nitrogen bond of the unstable thionitrite and subsequent
coupling of the resultant thiyl radicals.11
Although the reaction occurs without wet SiO2, the reaction time is
very long and the reaction is completed only after several days. There-
fore, we think that the presence of wet SiO2 will act as a media and will
provide a heterogeneous effective surface area for in situ generation of
HNO2. It also will make easy workup.
In conclusion, practical and efficient nitrosation–oxidation of thiols
was achieved by the present methodology. The cheapness and avail-
ability of the reagents, easy procedure, and workup make this method
attractive for the organic chemists. We believe that the present method-
ology addresses the current trend toward green chemistry due to high
yields and nontoxic wastes.
EXPERIMENTAL SECTION
General
Chemicals were purchased from Fluka, Merck, Riedel-deHaen AG, and
Aldrich Chemical companies. Silica chloride was synthesized according
to the reported procedures.4 Disulfides were characterized by compari-
son of their spectral (IR, 1H-NMR, UV and TLC) and physical data with
authentic samples.8–14,17,18

2180
M. A. Zolfigol et al.
TABLE I Coupling of Thiols to Their Corresponding Disulfides with a
Combination of Silica Phosphoric Acid (II), NaNO2 (III), and wt. SiO2 (50%
w/w) in Dichloromethane at Room Temperature
Reagent/Substratea
Substrate
Product
Time
Entry
1
2
(min) Yieldsb II (g)
III (mmol)
1
2
3
4
5
6
7
8
C6H5SH
C6H5CH2SH
FC6H4 SH
(C6H5S)2
20
40
35
60
6
1
30
25
99
91
92
99
85
70
92
85
0.7
0.7
0.7
0.7
0.55
1.4
0.8
0.7
2
2
2
2
2
2
2
2
(C6H5CH2S)2
(FC6H4 S)2
(C6H11 S)2
(HOCH2CH2 S)2
(ClC6H4 S)2
(C4H9 S)2
C6H11 SH
HOCH2CH2 SH
ClC6H4 SH
C4H9 SH
9
10
11
10
10
25
76c
70c
70c
0.7
0.7
0.7
4
4
4
(threo)
(threo)
aWet SiO2: substrate (0.2 g; 1 mmol).
bIsolated yields.
cWorkup with CH3OH and extracted with (Et2O/H2O).
Preparation of Silica Chloride (I)
Thionyl chloride (40 ml) was added to an oven-dried (120◦C, vacuum)
silica gel (10 g) in a round-bottomed flask (250 ml) equipped with a
condenser and a drying tube and refluxed for 48 h. The unreacted
thionyl chloride was distilled off. The resulting white-grayish powder
was flame-dried and stored in a tightly capped bottle. This silica chlo-
ride can be used for months without loosing its activity. It should be
noted that the adsorption of water by silica chloride causes its con-
version to original silica gel by generation of HCl. The percentage of
chloride in the silica chloride was determined by acid-base titration
according to the following reaction. The librated HCl was titrated by
standard NaOH, and the amount of chloride in silica chloride was
calculated.19

Disulfides
2181
Preparation of Silica Phosphoric Acid (II)
H3PO4 (9.8 g, 0,1 mol) was added to a suspension of silica chloride I
(94.5 g) in CH2Cl2 (200 ml) and vigorously stirred for 2 h. Then the
reaction mixture was filtered and the residue washed with CH2Cl2 (2 ×
50 ml). Silica phosphoric acid was obtained as a white powder.
Typical Experimental Procedure
Silica phosphoric acid II (1.4 g), wet SiO2 (50% w/w) (0.4 g), and NaNO2
III (0.257 g, 4 mmol) were added to a solution of thiophenol ((entry 1)
0.220 g, 2 mmol) in CH2Cl2 (10 ml). The resulting mixture was stirred at
room temperature. A bright-red heterogeneous solution was obtained
immediately. Thionitrites were characterized by comparison of their UV
spectra with those reported in the literature.17,18 Typical spectra are as
follows: λmax (CH2Cl2): PhSNO, 380, 529, 570 nm. A pale-yellow solu-
tion was also obtained after 20 min and then filtered. Dichloromethane
was evaporated. The yield was 0.216 g (99%) of crystalline brownish
diphenyldisulfide, m.p. 58◦C (Lit17,18 m.p. 58–60◦C).
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