Diethylamine-catalyzed dimerization of thiols: An inexpensive and green method for the synthesis of homodisulfides under aqueous conditions

Article abstract of DOI:10.1080/00397910903531904

Under H₂O / Et₂NH / atmospheric oxygen conditions, thiols are converted to their respective homodisulfides within a few hours. The process is conducted at room temperature for quantitative dimerization of aromatic, benzylic, and aliphatic thiols without the use of any extra additive. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903531904

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Diethylamine-Catalyzed Dimerization
of Thiols: An Inexpensive and
Green Method for the Synthesis
of Homodisulfides Under Aqueous
Conditions
a
a
M. Saeed Abaee , Mohammad M. Mojtahedi & Somayeh Navidipoor
a
a
Chemistry and Chemical Engineering Research Center of Iran,
Tehran, Iran
Published online: 15 Dec 2010.
To cite this article: M. Saeed Abaee , Mohammad M. Mojtahedi & Somayeh Navidipoor (2010):
Diethylamine-Catalyzed Dimerization of Thiols: An Inexpensive and Green Method for the Synthesis
of Homodisulfides Under Aqueous Conditions, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 41:2, 170-176
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1
Synthetic Communications , 41: 170–176, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903531904
DIETHYLAMINE-CATALYZED DIMERIZATION OF
THIOLS: AN INEXPENSIVE AND GREEN METHOD
FOR THE SYNTHESIS OF HOMODISULFIDES UNDER
AQUEOUS CONDITIONS
M. Saeed Abaee, Mohammad M. Mojtahedi, and
Somayeh Navidipoor
Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran
2 2
Under H O / Et NH / atmospheric oxygen conditions, thiols are converted to their respect-
ive homodisulfides within a few hours. The process is conducted at room temperature for
quantitative dimerization of aromatic, benzylic, and aliphatic thiols without the use of
any extra additive.
Keywords: Aqueous conditions; disulfides; oxidation; thiols
[
1]
The disulfide moiety is found in many biologically important structures and is
considered as a useful synthon for certain organic synthetic transformations such
[2]
[3]
as sulfenylation of anions, protection of thiols, and oxidation of organic func-
[4]
tional groups. Homodisulfides are generally synthesized via oxidative coupling
[5]
of their corresponding thiols. Many procedures are offered for this conversion
[
including using halogen-containing reagents, metal ions, iodine, chromium-
6]
[7]
[8]
[
9]
[10]
[11]
based oxidants,
electrochemical methods,
nanoparticles.
permanganate-based reagents,
[13]
enzymatic procedures,
[14]
[12]
hydrogen peroxide,
However, many of these methods involve overoxidation of pro-
ammonium persulfate,
and
[15]
ducts, require difficult workup or isolation procedures, need stoichiometric amounts
of expensive and=or toxic reagents, and use strong oxidizing agents. As a result,
development of simple and straightforward environmentally friendly protocols
capable of smoothly transfering thiols to disulfides is of great interest.
The most inexpensive and safe source of oxidation is molecular oxygen, which
[
16]
is used in several procedures for transformation of thiols to disulfides. However,
in the available methods, use of solvents, catalysts, or additives is required. In the
framework of our investigations on the development of new environmentally benign
[
17]
synthetic procedures,
media for smooth transformation of functional groups.
we recently published a few articles on the use of aqueous
[
18]
In the present work, we
reveal a very straightforward and inexpensive procedure for rapid and efficient
Received September 21, 2009.
Address correspondence to M. Saeed Abaee, Chemistry and Chemical Engineering Research
Centre of Iran, P.O. Box 14335-186, Tehran, Iran. E-mail: abaee@ccerci.ac.ir
1
70

GREEN SYNTHESIS OF DISULFIDES
171
Scheme 1.
conversion of thiols to their respective homodisulfides using ambient air under
H O=Et NH conditions (Scheme 1). To our knowledge, this is the most inexpensive
2
2
and environmentally friendly procedure offered so far for conversion of thiols to
disulfides.
Table 1 highlights the results obtained from the experiments primarily conduc-
ted to optimize the reaction conditions for oxidative coupling of benzenethiol. Under
atmospheric air pressure and at ambient temperature, use of 20 mol% of Et NH in
2
1
mL of tap water gave optimized conditions for converting the starting thiol to
its respective disulfide 1a after 5 h (entries 1–4). Use of lesser amounts of the amine
entry 5) or water (entries 6 and 7) decreased the yield of 1a after the same time per-
(
iod, illustrating their crucial roles in the reaction. Alternatively, omission of either
Et NH (entry 8) or H O (entry 9) suppressed the reaction significantly. Even under
flow of O gas, product 1a was formed only in 30% yield under nonaqueous con-
2
2
2
ditions (entry 10). Other secondary amines (entries 11–14) and hexylamine (entry
15) more or less behaved equally well, while tertiary amines were unsuccessful in
inducing the same reaction even in longer time periods (entries 16 and 17), perhaps
[
19]
because of their lower solubility in water comparing to secondary amines.
We next used the optimized conditions to convert various thiols to their
respective homodisulfides as shown in Table 2. Benzenethiol (entry 1) and its
electron-releasing and electron-withdrawing derivatives (entries 2–5) all gave good
Table 1. Optimization of the conditions for oxidation of benzenethiol
a
Entry
Amine
Amine (mol%)
Medium
Yield (%)
1
2
3
4
5
6
7
8
9
Et
Et
Et
Et
Et
Et
Et
2
2
2
2
2
2
2
NH
Excess
100
50
H
H
H
H
H
H
H
H
2
O (1 mL)
O (1 mL)
O (1 mL)
O (1 mL)
O (1 mL)
O (0.5 mL)
O (0.2 mL)
O (1 mL)
—
99
99
99
99
73
80
70
0
NH
NH
NH
NH
NH
NH
2
2
2
2
2
2
2
20
10
20
20
—
Et
Et
2
NH
NH
100
100
20
18
30
b
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
2
—
Pyrrolidine
Piperidine
H
H
H
H
H
H
H
2
O (1 mL)
2
O (1 mL)
2
O (1 mL)
2
O (1 mL)
2
O (1 mL)
2
O (1 mL)
2
O (1 mL)
84
93
86
94
95
5
20
20
Morpholine
Diisopropylamine
Hexylamine
Triethylamine
Pyridine
20
20
20
20
16
a
b
GC yields.
Under O bubbling conditions.
2

172
M. S. ABAEE, M. M. MOJTAHEDI, AND S. NAVIDIPOOR
Table 2. H
2
O=Et
2
NH-mediated oxidation of thiols
Product
a
Entry
Thiol
Yield (%)
1
2
C
6
H
5
SH
99
96
6 4
(4-Me)C H SH
3
(3-MeO)C
6
H
4
SH
95
4
5
(2-Br)C
6
H
4
SH
97
95
6 4
(4-Cl)C H SH
6
7
C
6
H
5
CH
2
SH
96
94
(4-MeO)C
2-furylCH
6
4 2
H CH SH
8
2
SH
97
93
9
Me(CH
2 3 2
) CH SH
a
Isolated yields.
yields of products 1a–e within 5 h. Benzylic thiols (entries 6–8) were also converted
efficiently to products 1f–h after the same time under the conditions. To examine the
aliphatic thiols, pentane-1-thiol was subjected to oxidative dimerization, giving 1i in
9
3% yield after 4 h (entry 9). All reactions proceeded rapidly and efficiently at room
temperature and under atmospheric pressure of the ambient air, giving their respect-
ive single disulfides. Products were identified based on the comparison of their spec-
[
6a–c,7a,15,20,21]
tral data with those available in the literature.
Based on these observations, a simplified mechanistic pathway is proposed
through which the starting thiol is first deprotonated in aqueous Et NH medium
2
and then oxidized by atmospheric oxygen to its respective radical. The radicals are
subsequently dimerized to form the disulfide products (Fig. 1).
In summary, a very convenient and rapid procedure for conversion of thiols to
homodisulfides is offered. Besides the starting thiol and tap water, the only required
additive for the reaction to proceed is substoichiometic amounts of Et NH. As a
2
consequence, the method is very inexpensive, environmentally safe, and straight-
forward. These features make the method an interesting addition to the present

GREEN SYNTHESIS OF DISULFIDES
173
Figure 1. Suggested mechanistic overview of the reactions.
2 2
Table 3. H O=Et NH-mediated oxidation of thiols in comparison
with other methods
Conditions
Reaction medium
Yield (%)
a
Et
Et
2
NH
H
2
O
99
97
90
73
98
78
92
87
99
[
20]
3
N=ultrasound
DMF
DMSO
–
[
6b]
TMSCl
Al =KF=MW (heat)
SO
CSF=celite=O
VO(acac) =t-BuOOH=-15 C
[22]
2 3
O
[6c]
2
Cl
2
CH
2 2
Cl
[
7a]
2
MeCN
ꢀ
[7b]
2
ꢀ
CH
CH
2
Cl
Cl
2
2
[23]
HNO =0 C
3
2
[
2
13]
H
2
O
3 2
(CF ) CHOH
a
This work.
literature archive. We can reach a better conclusion by comparing the present
procedure with some other available methods as reflected in Table 3.
EXPERIMENTAL
Reactions were monitored by thin-layer chromatography (TLC) using
silica-gel-coated plates and ethyl acetate = hexane solutions as the mobile phase.
NMR spectra were obtained on a Bruker Ultra Shield (500-MHz) instrument as
CDCl solutions, and the chemical shifts are expressed as d units with Me Si as
3
4
the internal standard. All reagents were purchased from commercial sources and
were freshly used after being purified by standard procedures. All products are
known compounds.
Typical Procedure
A thiol (2 mmol) was added to a homogeneous mixture of Et NH (0.4 mmol,
2
2
5
0 mol%) and water (1 mL), and the mixture was stirred under a fume hood for
h at ambient atmosphere and room temperature. The course of the reaction was
monitored by TLC. The reaction mixture was diluted by Et O (5 mL) and extracted
2
by a saturated NaHCO (5 mL) and brine (5 mL) solution. The organic layer was
3
dried over Na SO and the volatile portion was removed under reduced pressure.
2
4,

174
M. S. ABAEE, M. M. MOJTAHEDI, AND S. NAVIDIPOOR
The residue was purified by column chromatography using silica gel and a EtOAc=
hexane (1:1) solution, if necessary.
Selected NMR Spectral Data
[
15] 1
1
,2-Di-4-tolyldisulfane (1b).
H NMR (CDCl ) d 2.41 (s, 6H), 7.19 (d,
3
1
3
J ¼ 7.9 Hz, 4H), 7.49 (d, J ¼ 7.9 Hz, 4H); C NMR (CDCl ): d 43.2, 114.4, 129.9,
3
1
31.0, 159.5.
[
20] 1
1
,2-Bis(3-methoxyphenyl)disulfane (1c).
H NMR (CDCl ) d 3.81 (s,
3
1
3
6
(
H), 6.80–6.82 (m, 2H), 7.12–7.14 (m, 4H), 7.25 (dd, J ¼ 7.7, 8 Hz, 2H); C NMR
CDCl ): d 55.7, 113.1, 113.6, 120.1, 130.4, 138.8, 160.5.
3
[20] 1
1,2-Bis(2-bromophenyl)disulfane (1d).
H NMR (CDCl ) d 7.12 (ddd,
3
J ¼ 1.5, 7.8, 8 Hz, 2H), 7.30 (ddd, J ¼ 1, 7.5, 8 Hz, 2H), 7.56–7.59 (m, 4H),
1
3
7
.24–7.27 (q, 2H); C NMR (CDCl ): d 121.6, 127.5, 128.4, 128.7, 133.4, 136.6.
3
[
6c] 1
1
,2-Dibenzyldisulfane (1f).
1
H NMR (CDCl ) d 3.69 (s, 4H), 7.32–7.37
3
3
(
m, 6H), 7.39–7.42 (m, 4H); C NMR (CDCl ): d 43.8, 127.9, 129.0, 129.9, 137.9.
3
[
7a] 1
1
,2-Dipentyldisulfane (1i).
H NMR (CDCl ) d 0.91 (t, J ¼ 7 Hz, 6H),
3
3
1
3
1
.36–1.42 (m, 8H), 1.70–1.73 (m, 4H), 2.72 (t, J ¼ 7.5 Hz, 4H); C NMR (CDCl ):
d 14.4, 22.7, 29.3, 31.1, 39.6.
ACKNOWLEDGMENT
The Ministry of Science, Research, and Technology of Iran is gratefully
acknowledged for partial financial support of this work.
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