Conversion of thiols to disulfides using a hexamethylenetetramine-bromine complex

Article abstract of DOI:10.1080/10426500600864254

Hexamethylenetetramine-bromine complex, a yellow-orange, very stable homogeneous solid, affects a mild and fairly general conversion of thiols to disulfides. Copyright Taylor & Francis Group, LLC.

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Phosphorus, Sulfur, and Silicon
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Conversion of Thiols
to Disulfides Using a
Hexamethylenetetramine-
Bromine Complex
Issa Yavari a b , Ali A. Rounaqi c & Loghman Moradi b
a Chemistry Department, Science & Research
Branch , Islamic Azad University , Ponak, Tehran,
Iran
b Chemistry Department , Tarbiat Modarres
University , Tehran, Iran
c Chemistry Department, Tehran North Branch ,
Islamic Azad University , Tehran, Iran
Published online: 01 Feb 2007.
To cite this article: Issa Yavari , Ali A. Rounaqi & Loghman Moradi (2006) Conversion
of Thiols to Disulfides Using a Hexamethylenetetramine-Bromine Complex,
Phosphorus, Sulfur, and Silicon and the Related Elements, 181:11, 2659-2662, DOI:
10.1080/10426500600864254
To link to this article: http://dx.doi.org/10.1080/10426500600864254
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Phosphorus, Sulfur, and Silicon, 181:2659–2662, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600864254
Conversion of Thiols to Disulfides Using a
Hexamethylenetetramine-Bromine Complex
Issa Yavari
Chemistry Department, Science & Research Branch,
Islamic Azad University, Ponak, Tehran, Iran and
Chemistry Department, Tarbiat Modarres University, Tehran, Iran
Ali A. Rounaqi
Chemistry Department, Islamic Azad University, Tehran North Branch,
Tehran, Iran
Loghman Moradi
Chemistry Department, Tarbiat Modarres University, Tehran, Iran
Hexamethylenetetramine-bromine complex, a yellow-orange, very stable homoge-
neous solid, affects a mild and fairly general conversion of thiols to disulfides.
Keywords Disulfide; hexamethylenetetramine-bromine complex; oxidation; thiol
INTRODUCTION
The conversion of thiols to the corresponding disulfides (oxidative S–S
coupling) is an important reaction and many stoichiometric reagents
such as dichromates,1 chlorochromates,2 manganese dioxide,3 diethyl
azodicarboxylate,4 halosilane-chromium trioxide,5 nickel peroxide,6
chromium peroxide,7 tetrabutylammonium cerium(IV) nitrate,8 sodium
perborate,9 and silver trifluoromethanesulfonate,10 which have been re-
ported to be effective oxidants for it. However, the susceptibility of the
disulfide bond to further oxidation narrows the choice of the reagent for
the oxidation of thiols to disulfides in good yields. The discovery of oxi-
dants that are able to achieve the thiol-to-disulfide conversion in a high
yield with a variety of substrates has a key importance for the develop-
ment of the synthesis of complex organic compounds. The oxidation of
alcohols by N-halogenoamines11−14 and N-halogenoamides15 has been
Received November 7, 2005; accepted May 27, 2006.
Address correspondence to Issa Yavari, Chemistry Department, Tarbiat Modarres
University, PO Box 14115-175, Tehran, Iran. E-mail: yavarisa@modares.ac.ir
2659

2660
I. Yavari et al.
reported, and these reagents are important as practical, stable sources
of active halogen, which can oxidize thiols to disulfide systems.
RESULTS AND DISCUSSION
In this article, we report the oxidation of thiols by
a
hexamethylenetetramine-bromine complex. Our results are shown in
Table I. This solid, an easily handled and storable reagent, allows
for the conversion of thiols to disulfides. These reactions share the
virtues of ease of operation; simplicity of product isolation; formation
of products in high yields; and absence of side reactions, including
over-oxidation and halogenation of the products. The conditions are
adaptable to both small- and fairly large-scale operation.
The hexamethylenetetramine-bromine complex can be readily pre-
pared by adding bromine to a chloroform solution of the amine. This
homogeneous, non-hygroscopic solid is very stable at r.t., is not affected
by ordinary exposure to light, air, or water; and has no offensive odor
of bromine or amine. The reagent is transformed during the reaction
to easily removable products and presents a convenient alternative to
other N-halogenoamines.
All reaction products were analyzed by IR and 1H NMR spectroscopy
and gas chromatography and were found to be identical with pure au-
thentic samples.
In conclusion, a hexamethylenetetramine-bromine complex is an ox-
idant, which promises to be economical, convenient, and efficient for a
wide variety of cases.
EXPERIMENTAL
All products are known compounds and were identified by comparison
of their physical and spectral data with those of authentic samples.
IR spectra were recorded as films, or as KBr pellets on a Shimadzo
460 IR spectrometer. Proton NMR spectra were recorded at 300 MHz
with a Bruker 300-AVANCE FT-NMR instrument with CDCl3 as a sol-
vent and Me4Si as an internal standard. A hexamethylenetetramine-
bromine complex was prepared as previously described.14 The reagents
and solvents used in this work were obtained from Fluka and used
without further purification.
The Oxidation of Methyl 4-Sulfanylbutanoate to Methyl
4-[4-(Methyloxy)-4-oxobutyl] Disulfanyl-Butanoate (10):
Typical Procedure
To a mixture of hexamethylenetetramine-2Br2 (4.6 g, 10 mmol, 15 mmol
active Br2), water (30 mL), and dichloromethane (30 mL) in a 250-cm3

Conversion of Thiols to Disulfides
2661
TABLE I The Oxidation of Thiols to Disulfides by a
Hexamethylentetramine-Bromine Complex in
Dichloromethane-Water (1:1) at 30◦C
Reaction Time
Substrate
Product
(min)
Yield (%)a
96
8
1
5
96
2
3
4
10
8
94
94
94
10
5
15
92
6
7
12
2
92
98
8
5
96
96
9
14
10
aYields refer to the isolated product: All products were identified by comparing
their IR, 1H NMR, and TLC with those of authentic samples.

2662
I. Yavari et al.
round-bottomed flask was added with stirring a mixture of methyl
4-sulfanylbutanoate (20 mmol) in CH2Cl2 (30 mL). The reaction mix-
ture was stirred at r.t. until the yellow color of the complex disappeared.
The organic layer (Solution A) was separated, the remaining aqueous
layer was washed twice with 20-mL portions of CH2Cl2, and the wash-
ings were added to the organic layer. The CH2Cl2 solution was washed
successively with diluted (1%) aqueous HCl, water, diluted (3%) aque-
ous sodium carbonate, and water. The dried (MgSO4) solution was con-
centrated to afford 10, which was of good purity without further purifi-
cation needed. IR (KBr) υmax (cm−1): 1730 (C=O), 1428, 1354, 1011. 1H
NMR (CDCl3) δ = 1.35–1.39 (4 H, m, CH2), 2.81–3.00 (8 H, m, OCH2
and SCH2), 4.03 (6 H, s, OMe). - 13C NMR (CDCl3): δ = 29.3 (CH2), 32.8
(OCH2), 33.6 (SCH2), 51.6 (OMe), 172.4 (C=O) ppm.
Accordingly, compounds 1–9 were prepared in 92–98% yields (see
Table I). 1H and 13C NMR spectra of the crude reaction mixtures clearly
indicated the formation of the disulfides. Any product other than disul-
fides could not be detected by NMR spectroscopy.
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