Preparation of disulfides by the oxidation of thiols using trichloroisocyanuric acid

Article abstract of DOI:10.1081/SCC-100104331

Thiols are readily oxidized to disulfides by a solution of pyridine, water, benzoic acid and trichloroisocyanuric acid in acetonitrile and methylene chloride.

Full text of DOI:10.1081/SCC-100104331

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PREPARATION OF DISULFIDES BY THE OXIDATION OF
THIOLS USING TRICHLOROISOCYANURIC ACID
a
b
Ping Zhong & Meng-Ping Guo
a
Department of Chemistry , Wenzhou Normal College , Xueyuandong Road, Wenzhou,
25000, P.R. China
3
b
Department of Chemistry , Yichun Teachers College , 587 Huanchengxi Road, Yichun,
36000, P.R. China
3
Published online: 16 Aug 2006.
To cite this article: Ping Zhong & Meng-Ping Guo (2001) PREPARATION OF DISULFIDES BY THE OXIDATION OF THIOLS USING
TRICHLOROISOCYANURIC ACID, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 31:12, 1825-1828, DOI: 10.1081/SCC-100104331
To link to this article: http://dx.doi.org/10.1081/SCC-100104331
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SYNTHETIC COMMUNICATIONS, 31(12), 1825–1828 (2001)
PREPARATION OF DISULFIDES
BY THE OXIDATION OF THIOLS USING
TRICHLOROISOCYANURIC ACID
Ping Zhong1,2,* and Meng-Ping Guo2
1
Department of Chemistry, Wenzhou Normal College,
Xueyuandong Road, Wenzhou, 325000, P.R. China
2
Department of Chemistry, Yichun Teachers College,
587 Huanchengxi Road, Yichun, 336000, P.R. China
ABSTRACT
Thiols are readily oxidized to disulfides by a solution of pyr-
idine, water, benzoic acid and trichloroisocyanuric acid in
acetonitrile and methylene chloride.
1
–3
Disulfides are important reagents in organic synthesis
and many
methods for the synthesis of disulfides have been published. The oxida-
4
–7
5
–7
tion of a thiol to a disulfide is one of the most important,
reagents can be used to oxidize thiols to disulfides, such as bromine,
and many
5
6
dimethyl sulfoxide and clayfen. Trichloroisocyanuric acid [1,3,5-tri-
7
chloro-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione] 2 has been a useful reagent
8
in organic synthesis, it has been used to oxidized secondary alcohols to
9
ketones in good yields. We have now found that trichloroisocyanuric acid
[1,3,5-trichloro-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione] (2) is very efficient,
highly selective reagent for oxidation of thiols into disulfides.
*
Corresponding author.
1
825
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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REPRINTS
1
826
ZHONG AND GUO
A solution of a thiol 1, pyridine, water, benzoic acid and 2 in aceto-
nitrile and methylene chloride underwent oxidation to produce the corre-
sponding disulfide 3 along with cyanuric acid 4 and hydrogen chloride.
Yields are good to excellent (Scheme 1 and Table 1).
R ¼ Ph, 4-MeC H , 4-ClC H , 4-MeOC H , PhCH , n-C H , n-C H ,
6
4
6
4
6
4
2
4
9
6
13
n-C H .
2
1
25
Scheme 1.
Although acetonitrile generally worked well, in some instances other
solvents such as methelene chloride were more suitable due to that some
thiols have relatively poor solubility in acetonitrile. To enhance the rate
of oxidation a trace of water was added to the thiol reaction mixture.
But excessive water will reduce the rate of oxidation and give poor yields.
Without benzoic acid in the reaction the products 3 were produced in only
50–60% along with a few byproducts. Since hydrogen chloride is produced in
the reaction, and it can then react with 2 to form chlorine, pyridine is used
to react with hydrogen chloride to form pyridine hydrochloride.
1
0
Table 1. Synthesis of Compounds 3a–h
ꢀ
a
ꢀ
b
Product
R
m.p. ( C)
m.p. (lit.) ( C)
Yield (%)
7
3
3
3
3
3
3
3
3
3
a
a
b
c
d
e
f
Ph
Ph
60–61
60–61
45–46
70–71
43–44
71–72
Oil
60
91
59
89
81
83
76
75
77
80
c
7
60
7
4-MeC
4-ClC
4-MeOC H
PhCH
n-C
n-C H
6
H
4
46
70–71
7
6
H
4
1
1
44–45
7
72
6
4
2
4
H
9
Oil
Oil
g
h
Oil
31–32
6
13
7
32
n-C12
H
25
a
1
b
All products are characterized by H NMR, IR and m.p. Crystallized from etha-
c
nol. Without benzoic acid.

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OXIDATION OF THIOLS TO DISULFIDES
1827
1
Table 2. IR and H NMR Spectra Data for Disulfides 3
ꢁ
1
)
1
3
IR (KBr), ꢀ (cm
H NMR (CDCl /TMS), d (ppm)
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
3050, 1580, 1470, 780
2920, 1630, 1385, 795
3060, 1465, 1005, 800
2930, 1640, 1380, 820
3050, 2900, 1590, 820
2940, 2890, 1378, 730
2920, 2850, 1370, 725
2910, 2850, 1375, 720
7.0–7.6 (m, 10H)
2.29 (s, 6H), 6.86–7.30 (q, J ¼ 8 Hz, 8H)
7.10–7.60 (m, 8H)
3.70 (s, 6H), 6.90–7.50 (q, J ¼ 8 Hz, 8H)
3.48 (s, 4H), 7.15 (s, 10H)
0.98 (t, 6H), 1.25 (m, 8H), 2.60 (t, 4H)
0.89 (t, 6H), 1.43 (m, 16H), 2.65 (t, 4H)
0.88 (t, 6H), 1.43 (M, 40H), 2.66 (t, 4H)
g
h
Although the ease of the reactions is dependent on the electrosteric
properties of the thiols, it should be emphasized that the reactions could
been performed cleanly and controlled to stop at the disulfides stage. No
over-oxidation has been observed in any instance, even when the reactions
were carried out with an excess of the reagent and different solvent media.
In view of the easily available starting materials, good yield, mild and
neutral conditions, we feel that the present work described herein may
provide a useful method for the preparation of disulfides.
EXPERIMENTAL
1
H NMR spectra were recorded on PMX-60 spectrometer in CDCl as
3
the solvent with TMS as an internal standard. IR spectra were determined
using a VECTOR 22 as neat films. Silica gel 60 GF254 was used for analy-
tical and preparative TLC. All products were characterized by comparison
1
with authentic samples using IR, H NMR and m.p.
General procedure for the synthesis of 3a–h: In a 25 ml two-neck flask
were placed 2 mmol of thiol 1, 2 mmol of benzoic acid, 2 ml of acetonitrile,
2
ml of methylene chloride and 0.1 ml of water. The mixture in flask was
allowed to stir for 5 min before the addition of the solution of 2 was started.
The solution of 2 (1.5 mmol) in 1 ml of acetonitrile was added dropwise
through a syringe. After a few minutes, the reaction temperature began to
rise. The addition took a total of 30 min and that was followed by an
ꢀ
additional 30 min of stirring at 40 C. Excess 2 was destroyed by the slow
addition of saturated NaHSO solution. During this process, wet iodide-
3
starch test paper was used to periodically test for the presence of oxidizing
power. The precipitate of cyanuric acid 4 was removed by filtration
and washed with diethyl ether. Most of the solvent was removed from the

ORDER
REPRINTS
1
828
ZHONG AND GUO
filtrate with a rotary evaporator and the residue was diluted with 20 ml
of diethyl ether. The ether solution was washed with 1 N NaOH
(
dried over MgSO . After filtration and concentration, the crude product was
2 ꢂ3 ml), 1 N HCl (2 ꢂ 3 ml), and saturated NaCl solution (2 ꢂ 3 ml) and
4
purified by preparative TLC on silica gel and eluted with hexane and ethyl
acetate (20/1).
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Received in the USA August 29, 2000

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