Oxidative dimerization of thiols to disulfide using recyclable magnetic nanoparticles

Article abstract of DOI:10.1007/s11164-016-2718-1

Abstract: Dimerization of thiol groups to disulfide is an important transformation in chemical processes. In this study, magnetic ion exchanged Montmorillonite-k10 was synthesized and characterized using FTIR, X-ray diffraction and scanning electron microscope techniques. Then, the application of the synthesized catalyst as an efficient oxidizing agent was evaluated in oxidative dimerization of different thiols to corresponding disulfides under optimal reaction conditions. The reaction was easily performed with aromatic, aliphatic and heterocyclic thiols. The magnetic catalyst was easily recovered by applying an external magnet and, further, was reused in successive reactions. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11164-016-2718-1

Res Chem Intermed
DOI 10.1007/s11164-016-2718-1
Oxidative dimerization of thiols to disulfide using
recyclable magnetic nanoparticles
1
2
Nasrin Masnabadi
Mostafa Hossein Beyki
•
Mohammad Hadi Ghasemi
3
•
3
•
Mohammad Sadeghinia
Received: 18 May 2016 / Accepted: 27 August 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract Dimerization of thiol groups to disulfide is an important transformation in
chemical processes. In this study, magnetic ion exchanged Montmorillonite-k10 was
synthesized and characterized using FTIR, X-ray diffraction and scanning electron
microscope techniques. Then, the application of the synthesized catalyst as an efficient
oxidizing agent was evaluated in oxidative dimerization of different thiols to corre-
sponding disulfides under optimal reaction conditions. The reaction was easily per-
formed with aromatic, aliphatic and heterocyclic thiols. The magnetic catalyst was easily
recovered by applying an external magnet and, further, was reused in successive
reactions.
&
Nasrin Masnabadi
Masnabadi@riau.ac.ir; masnabadi2009@gmail.com
1
2
Rudehen Branch, Chemistry Department, Islamic Azad University, Tehran, Iran
Applied Chemistry Research Group, ACECR-Tehran Branch, P.O. Box 13145-186, Tehran,
Iran
3
School of Chemistry, University College of Science, University of Tehran,
P.O. Box 14155-6455, Tehran, Iran
123

N. Masnabadi et al.
Graphical Abstract
Keywords Thiol Á Disulfide Á Cation exchanged Montmorillonite Á Magnetic
nanoparticles Á Oxidative dimerization
Introduction
The conversion of thiols to the corresponding disulfides is an important reaction in
chemical processes. Disulfides have industrial applications as vulcanizing agents [1]
and are important synthetic intermediates with many applications in organic
synthesis [2, 3]. Disulfide bond formation is important in peptides [4] and bioactive
molecules [5]. Oxidative dimerization of thiols to disulfides under neutral and mild
conditions without overoxidation is an important process in organic chemistry [6]
and biochemistry [7], which has been investigated over the years. Many successful
reagents have been developed for the synthesis of disulfides without over-oxidation
of thiols to sulfoxides and sulfones [8]. Various reagents and oxidants have been
employed for the conversion of thiols to disulfides. This conversion has been
accomplished using reagents such as permanganates [9], sodium perborate [10],
ferric chloride [11], sodium chlorite [12], hydrogen peroxide [13], halogens [14],
molecular oxygen [15], PCC [16], ammonium persulfate [17], 2,6-dicarboxypyri-
dinium chlorochromate [18], 1,3-dibromo-5,5-dimethylhydantoin [19], N-phenyl-
triazolinedione [20], molecular bromine on hydrated silica gel support [21], iodine
and CeCl Á7H O in graphite [22], monochloro poly(styrenehydantoin) beads [23],
3
2
solid anhydrous potassium phosphate [24], cetyltrimethylammonium dichromate
25], sulfuryl chloride [26], benzyltriphenylphosphonium peroxymonosulfate [27],
[
silica-supported bis (trimethylsilyl) chromate [28], selenium ionic liquid [29], and in
the absence of any catalyst [30–32].
Clays function as efficient catalysts for various organic transformations due to
their catalytic activities in both their natural and ion-exchanged forms [33].
1
23

Oxidative dimerization of thiols to disulfide using…
Commercially available Montmorillonite K-10 (MMT) is environmentally benign
and an economically feasible solid catalyst that offers several advantages, such as
operational simplicity, non-corrosiveness, non-toxicity, low cost, easy isolation and
2
reusability [34]. Its high surface area (250 m /g) make it a useful and active catalyst.
Due to its structural features and synthetic potential, MMT has been used
extensively as a strong catalyst in organic synthesis [35] and has been emerging as a
very convenient support for a series of synthetic transformations.
Here, we extended our previous experience on solid supported reactions [36]. In
the course of studies on some reactions of MMT, we observed the oxidative
dimerization of thiols. In this study, we synthesized magnetically recoverable
3
?
cation-exchanged Al -Montmorillonite (Al-MMT) as an efficient catalyst (Fig. 1).
We have employed a simple, fast, and one-pot procedure with a simple workup for
efficient dimerization of a variety of thiols to their corresponding symmetrical
disulfides on Al-MMT without any reagents. A set of experiments were performed
to find the best conditions for the oxidation, using thiophenol as a model compound.
Experimental
Materials and methods
All the products were characterized by comparing their physical and spectral data
with those of known samples. All yields refer to isolated products. TLC experiments
were carried out on silica gel plates with a UV indicator from Aldrich, visualization
was by UV fluorescence or by staining with iodine vapor. IR spectra were recorded
on a Bruker Vector 22 FT-IR spectrophotometer using KBr disks or as neat samples.
The morphology of the catalytic particles was checked employing a scanning
electron microscope (AIS2300C SEI) at an accelerating voltage of 20 kV. The
X-ray diffraction (XRD) patterns were reported with a Philips X’Pert MPD
diffractometer equipped with Cu Ka radiation (k = 0.154 nm) in the range 10°–80°
(
2h) at a speed of 0.05°/min. Montmorillonite K-10 (MMT) having a surface area
2
50 m /g was purchased from Aldrich Chemical. All chemicals were also available
2
from Aldrich and used as purchased.
3
Fig. 1 Synthesis of magnetic Al -Montmorillonite (Al-MMT)
?
123

N. Masnabadi et al.
Catalyst preparation
Cation-exchanged MMT was synthesized and analyzed according to the literature
37]. MMT (5.00 g) was added gradually to a solution of aluminum nitrate (0.3 M,
0 ml) in a 250-ml flask equipped with a condenser and mechanical agitator, and
[
8
stirred for 4 h at room temperature. Then, the solid precipitate was filtered, washed
with water (2 ml 9 80 ml) and dried in a vacuum oven for 2 h at 100 °C. Finally, it
was calcinated in an oven for 3 h at 300 °C to obtain Al-MMT.
The co-precipitation method was performed for the magnification of cation-
exchanged MMT using ultrasonic waves. Al-MMT (5.0 g), FeCl Á4H O (9.94 g,
2
2
5
0 mmol,) and FeCl Á6H O (0.27 g, 100 mmol) were added to distilled water
3
2
(
100 ml) in a 250-ml flask equipped with a condenser and mechanical agitator under
nitrogen gas flow, and stirred for 30 min. Then, a concentrated ammonia solution
3.5 M) was added dropwise within 1 h under ultrasonic irradiation and refluxed for
h at 80 °C. After cooling, the magnetic precipitate was isolated from the reaction
mixture with a strong magnet, washed with water (5 ml 9 100 ml) and was at
(
1
80 °C in an oven for 12 h to obtain Al-MMT. The SEM images and FT-IR spectra
of MMT and Al-MMT are displayed in Figs. 2 and 3.
The X-ray diffraction patterns of Al-MMT are shown in Fig. 4. The XRD spectra
show that amorphous silica is the most dominant peak.
Optimization of synthesis conditions using catalysts
After synthesis and characterization of the magnetic catalyst, its effect on oxidative
dimerization of thiols was examined. A homogeneous mixture of thiophenol
(
0.55 g, 5 mmol) and Al-MMT (1.0 g) in tetrahydrofuran (10 ml) as a solvent was
stirred at 50 °C for 2 h (Table 1). The progress of the reaction was monitored by
TLC until complete disappearance of the starting material. After completion of the
reaction, the mixture was cooled to room temperature. The catalyst system was
removed from the reaction mixture with a strong external magnet, washed with
ethanol (10 ml) and diethyl ether (10 ml) and dried in an oven. Tetrahydrofuran was
concentrated under vacuum to yield the corresponding disulfide (1.05 g, 96 %). If
necessary, the product was further purified by column chromatography over silica
Fig. 2 SEM images of a MMT and b Al-MMT
1
23

Oxidative dimerization of thiols to disulfide using…
Fig. 3 FT-IR spectra of a MMT and b Al-MMT
Fig. 4 XRD pattern of Al-MMT
Table 1 Oxidative
dimerization of thiophenol with
b
Entry Catalyst
Solvent
Time (min) Yield (%)
a
different catalysts
1
2
3
4
5
6
7
8
9
1
1
MMT
Dichloromethane 120
71
88
83
85
5
Al-MMT Dichloromethane 120
Al-MMT Acetonitrile
Al-MMT Diethyl ether
Al-MMT Ethanol
120
120
120
120
120
120
Al-MMT Toluene
34
75
80
96
63
90
a
Reactions conditions:
thiophenol (5 mmol, 0.55 g),
catalyst (0.1 g), solvent (10 ml),
Al-MMT Acetone
Al-MMT Ethyl acetate
5
b
0 °C
Isolated yield
Al-MMT Tetrahydrofurane 120
Al-MMT Tetrahydrofurane 120
c
0
1
c
The reaction was performed at
room temperature
Al-MMT Tetrahydrofurane
60
123

N. Masnabadi et al.
gel (eluent: hexane/dichloromethane) or by bulb to bulb distillation. The above-
mentioned oxidation procedure for thiophenol is representative of all thiols
presented in Table 2.
Results and discussion
In this study, the cation exchange process in MMT resulted in increased acidity. As
a result, the reaction yields were increased (Table 1). Electron transfer between the
aluminum ions existing between MMT layers can activate the thiol functionality to
oxidative dimerization of sulfurs (Fig. 5). The difference between MMT and Al-
MMT was identified by investigating more reactions. Al-MMT as a Lewis acid can
act as a promising alternative for the Brønsted acids as an acid catalyst.
To complement the findings, a series of different thiols were employed in this
study, and the results are presented in Table 2. The results of the oxidation reactions
of these thiols presented in Table 2 indicate that the present method is equally
applicable for the oxidative coupling of alkyl thiols (Table 2, entries 1, 2), aryl
thiols (Table 2, entries 3–14), and heterocyclic thiols (Table 2, entries 15, 16).
Excellent results in thiol dimerization to disulfides was observed, except for
2
-thionaphthol, which was probably due to steric hindrance caused by the bulky
naphthyl group (Table 2, entry 11). The reactions were carried out under mild
conditions with excellent yields and simple workup. A simple separation of the
magnetic catalyst with an external magnet at the end of the reaction, followed by
removal of the solvent under reduced pressure from the filtrate, allows product
isolation. Impure products were purified utilizing column chromatography. Methyl,
methoxy, benzylic, carboxyl and halogen functionalities did not interfere with the
oxidation of the thiol group. As expected, sterically hindered thiols have slightly
lower yields compared to sterically unhindered thiols. High yields and high purity in
most cases were indicated by the TLC analysis and melting point compared with
those reported in the literature.
The FT-IR spectra were evaluated to analyze the functional groups of the
thiophenol and diphenyl disulfide (Fig. 6). The FT-IR spectrum shows that the
thiophenol was almost completely dimerized to diphenyl disulfide, so that the S–H
peak in thiophenol (Fig. 6a) was not observed in the product (Fig. 6b). EI Mass
spectrum of diphenyl disulfide is also shown in Fig. 7.
Reusability of catalyst
The reusability of Al-MMT was investigated in the oxidative dimerization of
thiophenol as a model. At the end of the reaction, Al-MMT was separated using an
external magnet, washed with dichloromethane and dried at 50 °C for 6 h. After
magnetic separation and product workup, the catalyst was reused for five successive
reactions, and the catalytic performance remained almost constant without any
remarkable decrease in catalytic activity (Fig. 8).
1
23

Oxidative dimerization of thiols to disulfide using…
a
Table 2 Oxidative dimerization of thiols to disulfide with Al-MMT as catalyst
Al-MMT / THF / 50 °C
R-SH
R-S-S-R
Time Yield
Ref
eren
ces
m.p.
(°C)
Entry
Thiol
Product
b
(min)
(%)
1
2
Et-SH
Et-S-S-H
60
88
Oil
Oil
[28]
S
S
60
60
91
96
[28]
SH
S
S
3
4
SH
59–60 [22]
73–74 [18]
S
S
Cl
SH
60
60
95
83
Cl
Cl
Cl
Cl
Cl
Cl
Cl
S
S
5
6
67–69 [29]
81–82 [10]
SH
SH
Cl
S
S
S
S
S
S
60
90
7
8
MeO
Me
SH
SH
60
80
92
86
43–44 [29]
41–43 [29]
MeO
Me
OMe
Me
Me
Me
Me
S
S
9
60
60
72
80
36–38 [28]
54–57 [29]
SH
Me
Me
S
S
S
S
Me
10
SH
SH
1
1
38–
40
1
1
2
120
90
65
90
[29]
SH
S
S
1
70–71 [29]
COOH
SH
COOH
COOH
S
S
288–
[18]
13
60
68
2
90
S
S
1
4
5
Br
SH
60
90
95
77
94–95 [18]
81–85 [36]
Br
Br
O
O
O
SH
S
S
S
S
1
SH
Me
N
N
Me
1
1
68–
70
16
N
N
90
78
[22]
N
N
Me
Me
Me
Me
a
Reactions conditions: thiole (5 mmol), catalyst (0.1 g), Tetrahydrofuran (10 ml), 50 °C
Isolated yield
b
123

N. Masnabadi et al.
Fig. 5 Oxidative dimerization of thiophenol using Al-MMT
Fig. 6 FT-IR spectra of a thiophenol and b diphenyldisulfide
Fig. 7 EI Mass spectrum of diphenyldisulfide
1
23

Oxidative dimerization of thiols to disulfide using…
Fig. 8 Recyclability of the catalyst Al-MMT in the oxidative dimerization of thiophenol
Conclusion
Cation-exchanged Montmorillonite (Al-MMT) has been used as a catalyst for many
organic reactions and has several advantages compared to conventional acids, such
as strong acidity, non-corrosive properties, mild reaction conditions, high yields and
selectivity. On the other hand, the magnetic property of magnetic nanoparticles in
the catalytic support facilitates the separation and recycling of the catalyst of the
reaction medium, more easily than filtration or centrifugation.
In conclusion, the method for oxidizing aliphatic, aromatic, and heteroaromatic
thiols with Al-MMT, as reported in this paper, is a simple, fast, efficient,
inexpensive, easy to handle, very mild procedure. In this study, we have developed a
mild, efficient and good yielding method for the oxidation of thiols. In addition,
rapid completion of the reactions, environmental safety of the process, high yields
of the products, simple separation of the magnetic catalyst, clean workup and
excellent purity of products are worthwihle advantages of the present method that
makes it an attractive and useful procedure for the oxidation of thiols to
corresponding disulfide compounds. Moreover, the method is applicable to a wide
variety of thiols, being a useful alternative to other methods in the literature.
Acknowledgment The authors appreciate the financial support of this investigation by ACECR—Tehran
branch.
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