Microwave-assisted synthesis of disulfides using tetrathiomolybdate: A step toward greener synthesis

Article abstract of DOI:10.1002/hc.21025

An eco-friendly, efficient, and rapid synthetic procedure for disulfides using benzyl triethyl ammonium tetrathiomolybdate through microwave irradiation of solid support adsorbed reactants is reported.

Full text of DOI:10.1002/hc.21025

Heteroatom Chemistry
Volume 00, Number 0, 2012
Microwave-Assisted Synthesis of Disulfides
Using Tetrathiomolybdate: A Step toward
Greener Synthesis
Naheed Sidiq, Mohsin Ahmad Bhat, Khaliquz Zaman Khan, and
Mohammad Akbar Khuroo
Department of Chemistry, University of Kashmir, Srinagar 190 006, India
Received 27 July 2011; revised 23 February 2012
compounds (VOCs) in this often opted procedure
ABSTRACT: An eco-friendly, efficient, and rapid syn-
for disulfide synthesis have been a great challenge
for environment-conscious synthetic chemists. Such
challenges in synthetic organic chemistry are usually
overcome through the use of unconventional reactor
thetic procedure for disulfides using benzyl triethyl am-
monium tetrathiomolybdate through microwave irra-
diation of solid support adsorbed reactants is reported.
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C
2012 Wiley Periodicals, Inc. Heteroatom Chem 00:1–4,
designs and reaction pathways that require the use of
2012; View this article online at wileyonlinelibrary.com.
nonhazardous and eco-friendly chemicals to ensure
DOI 10.1002/hc.21025
efficient and green synthesis of desired substances.
It is in this context that microwave irradiation cou-
pled with solid support is receiving considerable
INTRODUCTION
attention in organic synthesis [6–8]. The use of mi-
crowave irradiation in organic synthesis has ensured
minimal or no use of VOCs, simple workup coupled
with higher yields, shorter reaction times, low energy
consumption, and selectivity [9–13] in certain reac-
tions. In view of these facts and drawing an inspira-
tion from some recent reports [14,15], we attempted
the use of microwave irradiation in the synthesis of
disulfides from alkyl halides and thiocyanates us-
ing benzyl triethyl ammonium tetrathiomolybdate
(BTATM). In the present communication, we report
results from our preliminary investigations about
the synthesis of disulfides through microwave irra-
diation of solid-supported reactants. The main find-
ing of the present communication is that the use of
microwave irradiation turns the conventional syn-
thetic procedure of disulfides eco-friendly, efficient,
and time saving.
The synthesis and chemistry of disulfides continue
to be an area of considerable interest among re-
searchers on account of their biological role, indus-
trial applications, and utility in organic synthesis
[1–5]. Although a variety of methods have been
devised for their synthesis, disulfides are mostly
synthesized from the corresponding halides, thio-
cyanates, and alcohols using tetrathiomolybdate
[2,4]. This is due to advantages such as straight-
forward reaction methodologies and mild reaction
conditions that can be tuned green by careful and
intelligent modifications in the experimental proce-
dure. An appropriate choice of parameters in these
steps is expected to ensure the synthesis of disul-
fides through solventless and/or use of eco-friendly
solvent choices and biphasic catalysis pathways. The
disadvantages such as longer reaction times, opera-
tional complications, and the use of volatile organic
RESULTS AND DISCUSSION
Before attempting the microwave-assisted synthe-
sis, we explored the stability of silica-supported as
well as water-solubilized BTATM on exposure to
Correspondence to: Mohammad Akbar Khuroo; e-mail: khuroo
.mohammadakbar@gmail.com.
2012 Wiley Periodicals, Inc.
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Sidiq et al.
TABLE 1 Overall Yield for the Reaction of Benzyl Chloride,
Benzyl Thiocyanate, Benzyl Bromide, Hexyl Bromide, Octyl
Bromide at Different Time Durations with Composition of the
Reaction Mixture Based on GC-MS Analysis
microwave irradiation. For this purpose, these sam-
ples were irradiated at different power levels up
to the maximum of 300 s and temperatures were
recorded. It was found that the temperature reaches
a maximum of 80◦C in the case of BTATM in water
and 62◦C in the case of BTATM on silica gel. This
temperature is much less than the decomposition
temperature of BTATM (130–150◦C). The UV spec-
tra of pre- and postirradiated BTATM were found to
be identical, establishing that the BTATM is stable
under the microwave irradiation conditions that we
attempted in our experiments.
Our most solvent selections for thin-layer chro-
matography (TLC) analysis of product from the re-
actions carried out under conventional conditions
and microwave irradiation showed the product as
a single entity in accordance with earlier reports.
Incidentally, with a solvent choice of petroleum
ether:chloroform (7:3 v/v) revealed that the prod-
uct is a combination of two hard to separate en-
tities whose ratio apparently varied with the re-
action time. Earlier, Harpp and MacDonald have
also reported formation of an inseparable mixture
of mono- and disulfides from alkyl halides using a
molybdenum–persulfide complex [16]. Similar re-
sults using haloesters with BTATM and formation
of thiol in addition to disulfides with piperidinium
tetrathiomolybdate have been reported by Chan-
drasekaran and coworkers [4,17]. To confirm the
formation of two products in our case, the reaction
products were subjected to the gas chromatography–
mass spectrometry (GC-MS) analysis and we found
that the product is indeed a mixture of monosulfide
and disulfide of the starting compound wherein the
ratio of mono/di analog decreases with an increase in
the reaction time. Overall, the yield of each reaction
along with the percentage composition of different
products as determined by the GC-MS analysis is
presented in Table 1.
The GC-MS analysis of the product from the
reaction of benzyl chloride with BTATM revealed
the presence of two compounds with Kovet’s re-
tention indices 2068 and 1817 corresponding to
dibenzyl disulfide (DBDS) and dibenzyl monosul-
fide (DBS). The best yield of approximately 70.1%
was observed with an irradiation time of 300 s at
the medium–high power level. We observed that the
overall yield and proportion of DBDS in the prod-
uct increases with an increase in time and power
levels.
In the reaction of benzyl thiocyanate with
BTATM under similar reaction conditions, as men-
tioned for benzyl chloride, a yield of 98.3% in 300 s
at the medium–high power level with 100% fraction
of DBDS is formed. Again, in this case, the overall
%Composition
Time Overall
(s) Yield (%) (disulfide) (monosulfide)
RSSR
RSR
Substrate
Benzyl chloride
60
120
180
240
300
52.66
52.8
53.2
56.7
70.1
65.03
73.03
79.58
89.93
98.3
56.3
52.5
50.3
46.62
46.5
46.5
63.9
64.24
64.34
68.53
66
66.80
67.25
68.80
51.0
51.8
52.8
56.3
69.9
64.75
72.95
79.5
89.9
98.3
42.6
43.4
27.4
23.31
23.2
23.2
62.5
63.8
63.9
68.24
64.5
66.3
67.11
68.55
1.66
1.0
0.4
0.4
0.2
0.28
0.08
0.08
0.03
Benzyl thiocyanate 60
120
180
240
300
30
60
120
150
180
270
60
120
180
240
60
Benzyl bromide
13.7
9.1
22.9
23.31
23.3
23.3
1.4
0.44
0.39
0.29
1.5
Hexyl bromide
Octyl bromide
120
180
240
0.5
0.14
0.25
yield and proportion of DBDS was found to increase
with an increase in time and power levels.
For benzyl bromide with BTATM, the best yield
of 56.3% was observed with an irradiation time of
30 s at the medium–low power level and surpris-
ingly the amount of DBS increases (a decrease in the
DBDS:DBS ratio) when we move from the medium–
low to medium power level. However, switching to
the medium–high power level was found to decrease
the overall yield, perhaps on account of overheating,
leading to decomposition of the reactant/product.
With an increase in temperature from room tem-
perature to the medium–low power level under mi-
crowave irradiation, the reaction time is reduced but
the overall yield decreases, indicating the instability
of the reactant with increasing temperature.
In the reaction of hexyl bromide with BTATM,
the GC-MS analysis of the product revealed the pres-
ence of two compounds with Kovet’s retention in-
dices 1716 and 1465 corresponding to dihexyl disul-
fide and dihexyl monosulfide. The overall yield and
percentage composition of dihexyl disulfide increase
with an increase in time and power levels.
For the reaction of octyl bromide with BTATM,
the GC-MS analysis of the product revealed the
Heteroatom Chemistry DOI 10.1002/hc

Microwave-Assisted Synthesis of Disulfides Using Tetrathiomolybdate: A Step toward Greener Synthesis
3
presence of two compounds with Kovet’s reten-
tion indices 2113 and 1817 corresponding to dioctyl
disulfide (DODS) and dioctyl monosulfide. The over-
all yield as well as percentage composition of
DODS increases with increasing time and power
levels.
Interestingly, we found that the relative ratio of
disulfide:monosulfide changes with a change in the
irradiation time at all power levels.
case of benzyl chloride and benzyl thiocyanate,
the overall yield and percentage composition of
DBDS increase progressively with an increase in
time and power levels.
3. Microwave-assisted synthesis of disulfides us-
ing BTATM is an efficient, less time-consuming,
greener synthetic procedure as compared with
conventional conditions.
We also compared the efficiency of the
microwave-assisted procedure with the conventional
one for the synthesis of disulfides from the above-
mentioned substrates. A comparative account of the
two synthetic procedures is given in Table 2.
From the data, it is evident that for all the five
substrates, viz., benzyl chloride, benzyl thiocyanate,
benzyl bromide, hexyl bromide, and octyl bromide,
the higher percentage yields for their corresponding
disulfides were obtained under microwave irradia-
tion and in a much shorter time than under conven-
tional conditions.
CONCLUSIONS
For the first time through an eco-friendly proce-
dure, disulfides have been conveniently prepared
using alkyl halides and thiocyanates using BTATM
under solvent-free microwave conditions. With thio-
cyanate as the substrate, a maximum yield of 98.3%
has been obtained under microwave irradiation and
hence it is a suitable substrate for the synthesis of
disulfides. Because the reactions have been carried
out on a solid support with minimal involvement of
solvents, the procedure provides a green chemistry
approach.
From our observations in the present study, we
make following inferences:
EXPERIMENTAL
1. The overall yield as well as percentage yield of
DBDS is best achieved when benzyl thiocyanate
is used as a substrate as compared with benzyl
chloride and benzyl bromide. Its irradiation at
the medium–high power level for 300 s increases
the overall yield to 98.3% comprising 100% diben-
zyl disulfide. This can be best explained in terms
of inherent dipole of a molecule [18–20], viz.,
a higher dipole moment leads to efficient mi-
crowave heating. In the benzyl series of studied
compounds, the dipole moment is in the order
SCN− > Cl− > Br−, which explains the higher
yields in the case of benzyl thiocyanate than ben-
zyl bromide and benzyl chloride, respectively.
Reactions were performed in a Sharp Carousel TM
microwave oven (Thailand) (model R-210 B with
output power of 800 W). The GC-MS analysis was
carried on a Varian GC-3800 capillary column VF-
5 ms (60 m × 0.25 mm film thickness 0.25 μm)
coupled with a 4000 series mass detector (Applied
Biosystems/MDS Sciex) under the following con-
ditions: injection volume 0.5 μL with a split ra-
tio 1:60; helium as a carrier gas at 1.3 mL/min
constant flow mode; injector temperature 280◦C;
oven temperature 80◦–280◦C. In a typical synthetic
procedure, 1 mmol of the substrate and BTATM
(0.66 g, 1.1 mmol) in 1 mL of acetonitrile was ad-
sorbed on silica gel (60–120 mesh) used as solid sup-
port. Different reaction mixtures were prepared and
irradiated for different time durations at medium–
low, medium, and medium–high power levels. For
the reaction of benzyl bromide with BTATM, dif-
ferent mixtures were prepared and irradiated at
medium–low, medium, and medium–high power
levels for different time periods of 30, 60, 120, 150,
180, and 270 s. Irradiation was carried out in mul-
tiple heating cycles of 15 s, and progress of reac-
tion was monitored with TLC. The mixture of ben-
zyl chloride and benzyl thiocyanate with BTATM
on solid support was irradiated for 60, 120, 180,
240, and 300 s. In the reaction of hexyl bromide
and octyl bromide with BTATM, irradiation was car-
ried out in multiple heating cycles of 30 s. Because
the reactions were carried out under solvent-free
2. In the case of benzyl bromide, overall yield and
percentage composition of DBDS decrease with
increasing time and power level, whereas in the
TABLE 2 Comparative Data of Conventional and Microwave
Reactions
Room
Temperature
Microwave
Irradiation
Substrate
Time (h) Yield (%) Time (s) Yield (%)
Benzyl thiocyanate
Benzyl chloride
Benzyl bromide
Hexyl bromide
Octyl bromide
6
5
1
10
11
80
60
55
60
62
300
300
30
240
240
98.3
71
57
68.58
68.80
Heteroatom Chemistry DOI 10.1002/hc

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Sidiq et al.
conditions, irradiation of the same mixture at dif-
ferent time intervals that could have led to a change
in the concentration of reactants as well as the prod-
ucts was avoided. To maintain the concentration to
be considerably accurate for each substrate, we took
several equally concentrated reaction mixtures ad-
sorbed on the same amount of solid support and irra-
diated them at medium–low, medium, and medium–
high power levels for various time durations.
Reactions were monitored periodically with TLC. Af-
ter irradiating for specified durations, reaction mix-
tures were eluted with diethyl ether (3 × 20 mL). The
concentration of the ethereal layer yielded a white
color solid/colorless liquid. Solids were crystallized;
melting points recorded, and the percentage yield
at different time durations and power levels were
obtained.
Dioctyl monosulfide: MS (m/z): 258 (M+),159,
1
145, 112, 83. H NMR (200 MHz, CDCl3): 2.40 (t,
4H), 1.27–1.59 (m, 24H), 0.96 (t, 6H). bp 180◦C/10
mmHg.
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The analytical data for products are as follows:
BTATM: UV–visible (DMF): λ max: 279, 342, 468.
IR (KBr, cm−1): 3036, 2969, 1508, 1473, 1450, 1392,
1373, 1153, 1010, 788, 750, 704, 468 (Mo-S). mp:
130◦C
Dibenzyl disulfide: MS (m/z): 246 (M+), 182, 121,
91. 1H NMR (200 MHz, CDCl3): 7.28 (s, 10H), 3.60 (s,
4H). IR (KBr, cm−1): 3049, 3025, 2922, 2853, 1597,
1491, 1451, 1382, 1222, 1120, 658. mp: 70◦C.
Dibenzyl monosulfide: MS (m/z): 214 (M+), 182,
1
121, 91. H NMR (200 MHz, CDCl3): 7.17 (s, 10H),
3.45 (s, 4H). IR (KBr, cm−1): 3110, 3080, 3050, 2940,
1625, 1600, 1505, 1462, 1430, 1232, 1205, 1070, 1030.
mp: 49◦C.
Dihexyl disulfide: MS (m/z): 234 (M+), 154, 117,
81. 1H NMR (200 MHz, CDCl3): 2.5 (t, 4H), 1.26–1.65
(m, 16H), 1.2 (t, 6H). bp: 300◦C.
Dihexyl monosulfide: MS (m/z): 202 (M+), 131,
117, 84, 69, 61, 55, 43, 29. 1H NMR (200 MHz,
CDCl3): 2.4 (t, 4H), 1.29–1.66 (m, 16H), 1.2 (t, 6H).
bp: 220◦C.
Dioctyl disulfide: MS (m/z): 290 (M+), 178, 145,
1
112, 87, 71, 57. H NMR (200 MHz, CDCl3): 2.46 (t,
4H), 1.29–1.59 (m, 24H), 0.96 (t, 6H). bp: 240◦C/10
mmHg.
Heteroatom Chemistry DOI 10.1002/hc