668 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 668^669y
Efficient Conversion of Thiols to S-Nitrosothiols
with the 18-Crown-6 Complex of N O as a New
Nitrosating Agenty
N. Iranpoor,* H. Firouzabadi* and R. Heydari
Chemistry Department, College of Sciences, Shiraz University, Shiraz 71454, Iran
Gaseous N2O4 reacts with 18-crown-6 to afford a stable ionic complex of NO Á18-crown-6ÁHꢀNO3 ; this
2
complex is an efficient nitrosating agent for the conversion of thiols to their corresponding S-nitrosothiols in
different organic solvents.
S-Nitrosothiols are an interesting class of organic com-
pounds1 and are becoming increasingly useful not only
as a source of thiyl radicals2 or as nitrosating reagents3
but also as vasodilatory drugs due to their therapeutic
use and their remarkable physiological importance.4 One
of the problems encountered in the synthesis of
S-nitrosothiols is their low stability and their ease of con-
version to the corresponding disul¢des due to the oxidative
Table 1 Reaction of thiols with NO Á18-crown-6ÁHꢀNO3
tert-butanol at room temperaturea
in
2
Thiol
Productb
l
max/nm/Absorbancec
1a
1b
1c
1d
1e
1f
MeCH23SNO
PhSNO
Cyclohexyl-SNO
MeCH26CH2SNO
EtSNO
ONSCH2CH2CH2SNO
PrSNO
PhCH2SNO
339/1.99, 551.2/0.09
378/0.91, 572/0.16
342/0.76, 557/0.06
339/2.89, 551/0.12
337/2.8, 552/0.12
339/1.4, 551/0.11
343/1.67, 600/0.14
341/2.65, 550.4/0.07
8
ability of the reaction media.2;5
As a source of nitrosonium ion, gaseous dinitrogen
tetroxide ꢀN2O4 has also been used for this transformation.
However, control of the reaction with this gas is important
and the intermediate S-nitrosothiol can be converted to
disul¢des or other oxidative products. In our recent report
on the use of CuꢀNO32 Á N2O4 as a nitrosating agent,
the presence of CuII enhances the rapid conversion of
the resulting S-nitrosothiol to the disul¢de.6 In order to
eliminate this problem, a study upon the use of dinitrogen
tetroxide derivatives as a source of nitrosonium ion is
important. We have recently demonstrated the applicability
1g
1h
a The reactions occurred immediately. bThe products were not
isolated and were identified by comparison of their UV and IR
spectral data with the literature. All products show a weak
c
absorption band at about 520 nm.
Experimental
Products were characterised by comparison of their UV and IR
spectral data with those of known samples in the appropriate solvent
without isolation. UV spectra were recorded on a Pye Unicam 8725
spectrometer and samples were taken from the reaction mixture in
tert-butanol. IR spectra were recorded on a Perkin Elmer IR-157
G or a Perkin Elmer 781 spectrometer and the samples were taken
from the reaction mixture using CCl4 as solvent.
of
the
crystalline
ionic
for the selective nitration
now report that
in solvents such as ethyl
complex
of
9
NO Á 18-crown-6 Á HꢀNO3
of
phenols.10
We2
NO Á 18-crown-6 Á HꢀNO3
acetate, diethyl ether, ter2t-butanol, carbon tetrachloride
and dichloromethane reacts immediately with thiols at room
temperature and produces the corresponding S-nitrosothiol.
The reaction in tert-butanol is more advantageous than the
other solvents in this study in which the reaction mixture
solidi¢es on freezing and can be stored for days without
change.11 UV and IR spectral analysis of the products in
solution showed the characteristic bands for the thionitrite
group which are similar to those reported in the literature8
(Scheme 1 and Table 1).
Typical Procedure.öTo a stirred solution of thiophenol (0.11 g,
1 mmol) in tert-butanol (5 ml), NO Á 18-crown-6 Á ꢀNO3
(0.42 g,
1 mmol) was added at room temperature. The reaction was2completed
immediately and a bright red solution was obtained. UV and IR
spectral data of the product in tert-butanol were compared with
the reported data in the literature. The frozen mixture can be stored
for several days without any change.
We are grateful to the Shiraz University Research Coun-
cil for the partial support of this work.
Received, 15th June 1999; Accepted, 27th July 1999
Paper E/9/04784K
–
NO+•18-crown-6•H(NO3)2
RSH
RSNO
1
2
a R = n-C4H9
e R = Et
References
b R = Ph
f R = –CH2CH2CH2–
g R = Prn
1
(a) D. L. H. Williams, The Chemistry of Amino, Nitroso, Nitro
and Related Groups, Wiley, New York, 1996, pp. 665^682, and
references cited therein; (b) L. K. Keefer and D. L. H.
Williams, Methods in Nitric Oxide Research, Wiley, New
York, 1966, pp. 509^519.
c R = cyclohexyl
d R = n-octyl
h R = PhCH2
Scheme 1
2
3
S. Oae, Y. H. Kim and D. Fukushima, Chem. Lett., 1977, 893.
S. S. Al-Kaabi, D. H. L. Williams, R. Bonnett and S. L. Ooi,
J. Chem. Soc., Perkin Trans. 2, 1982, 227.
In conclusion, the present reagent is an e¤cient, stable
and solid source of N2O4 for the conversion of thiols to
the corresponding S-nitrosothiols. The reactions can pro-
ceed in a variety of solvents under mild reaction conditions.
The handling of the reagent is also very easy.
4
(a) S. Oae, K. Shinhama, Org. Prep. Proc. Int., 1983, 15, 165;
(b) S. Monocada, R. M. J. Palmer and E. A. Higgs,
Pharmacol. Rev., 1991, 43, 109; (c) P. L. Feldman, O. W.
Gri¤th and J. Stuehr, Chem. Eng. News, 1993, 20, 26.
A. Cornelis, N. Depaye, A. Gerstmans and P. Laszlo,
Tetrahedron Lett., 1983, 24, 3103 and references cited therein.
N. Iranpoor, H. Firouzabadi and M. A. Zol¢gol, Synth. Com-
mun., 1998, 28, 367.
5
6
7
* To receive any correspondence.
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).
H. Firouzabadi, N. Iranpoor and A. Zol¢gol, Synth. Commun.,
1998, 28, 1179.
Iranpoor
