Synthesis of sulfides under solvent- and catalyst-free conditions

Article abstract of DOI:10.1007/s00706-008-0043-0

A simple, highly efficient, and green protocol has been developed for preparation of sulfides from alkyl or aryl thiols and benzyl-, allyl-, t-butyl, and adamantyl halides under solvent- and catalyst-free conditions.

Full text of DOI:10.1007/s00706-008-0043-0

Monatsh Chem (2009) 140:409–411
DOI 10.1007/s00706-008-0043-0
ORIGINAL PAPER
Synthesis of sulfides under solvent- and catalyst-free conditions
Barahman Movassagh Æ Mohammad Soleiman-Beigi
Received: 8 June 2008 / Accepted: 8 July 2008 / Published online: 17 September 2008
Ó Springer-Verlag 2008
Abstract A simple, highly efficient, and green protocol
has been developed for preparation of sulfides from alkyl
or aryl thiols and benzyl-, allyl-, t-butyl, and adamantyl
halides under solvent- and catalyst-free conditions.
thiols with benzyl halides under solvent- and catalyst-free
conditions.
Sulfides are a class of important synthetic reagents and
intermediates in organic, medicinal, bio-organic, and het-
erocyclic chemistry [5–7]. Also, they are the starting
compounds for the preparations of other sulfur compounds,
such as sulfoxides, sulfones, and sulfonium compounds, etc.
Keywords Neat Á Solvent-free Á Catalyst-free Á
Sulfides Á Thiols
[
8]. Numerous procedures exist for the preparation of sul-
fides, including desulfurization of disulfides, aryllithium or
organocuprate addition to thiocarbonyl compounds, reduc-
tion of sulfoxides and sulfones [9, 10]; nucleophilic
displacement of aryl and alkyl halides by thiolate ion
[11–13]; treatment of thiols and alkyl halides with DBU
[14], or cesium carbonate and tetrabutylammonium iodide
[15]; the treatment of alkyl halides with sodium sulfide [16],
thiourea [17], or thiocarbonate [18]; the reaction of halides
with thiosilanes [19]; ring-opening of epoxides with thiols
[20], and disulfides [21]; Michael addition of thiols [22] and
disulfides [23] to a,b-unsaturated carbonyl compounds;
intermolecular S-alkylation of thiols with alcohols [24]; the
reaction of thiolate anions, generated in situ by indium(I)
iodide promoted cleavage of dialkyl/diaryl disulfides, with
styrenes [25]. Because of various disadvantages such as use
of hazardous and toxic solvents, difficulty in recovery of
high boiling solvents, use of costly catalysts, etc., encoun-
tered in the reported methodologies, we decided to develop
a more convenient and eco-friendly method.
Introduction
In practice, from an ecological point of view, the best
solvent is without a doubt no solvent. There are of course a
great many reactions that can already be carried out in the
absence of solvent. Reports on solvent-free reactions have,
however, become increasingly frequent and specialized
over the past few years. The field of solvent-free organic
synthesis covers all branches of organic chemistry. It
includes stochiometeric solid–solid reactions [1] and gas–
solid reactions [2], and supported inorganic reagents [3],
which in many cases are accelerated or even made possible
through microwave irradiation [4]. There are also reactions
in which at least one reactant is liquid under the conditions
employed, which means that the solvent that would nor-
mally be used can simply be left out.
As part of our research to develop practical, simple, and
green methodologies in organic synthesis, we report here a
convenient route to the preparation of benzyl sulfides of
general formula PhCH SR through a simple coupling of
2
Results and discussion
B. Movassagh (&) Á M. Soleiman-Beigi
Department of Chemistry,
K. N. Toosi University of Technology,
P. O. Box 16315-1618, Tehran, Iran
e-mail: bmovass1178@yahoo.com
In order to optimize the reaction condition with respect to
temperature, and time, we first studied the reaction of
thiophenol (1.1 mmol) with benzyl bromide (1.0 mmol) as
a model reaction in the absence of catalyst under neat
123

4
10
B. Movassagh, M. Soleiman-Beigi
neat
Table 2 Synthesis of sulfides 3 under solvent- and catalyst-free
conditions at 100 8C
PhSH + PhCH Br
PhSCH Ph
2
2
1
2
R X
a,b
Entry
R
Time (h) Yield (%)
Scheme 1
1
2
2
2
2
2
2
1
2
2
2
2
2
2
2
5
6
7
6
6
8
6
5
8
8
8
8
9
6
6
1
2
3
4
5
6
7
8
9
4-BrC
6
H
4
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
2
2
2
2
2
2
2
2
2
2
2
2
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
8
16
80
90
86
96
92
82
66
78
30
53
61
77
83
87
81
62
3 6 4
4-CH C H
Table 1 Reaction of thiophenol with benzyl bromide at various
temperatures
2-Naphthyl
32
a
Ph
16
Entry
Temperature (°C)
Time (h)
Yield (%)
4-ClC
6
H
4
12
1
2
3
4
5
50
50
13
23
19
10
16
53
72
73
74
96
4-CH OC
3
6
H
4
22
PhCH
2
28
70
HOCH
2
CH
2
11
90
n-C
n-C
n-C
4
H
6
H
8
H
9
39
100
1
1
1
1
1
1
0
1
2
3
4
5
13
38
38
Molar ratios of thiophenol:benzyl bromide = 1.1:1
a
Isolated yield
17
4-CH OC
3
6
H
4
28
4-ClC
4-ClC
Ph
6
H
4
4
4-NO
PhCH
PhCH
2
C
6
H
4
CH
2
Br 30
6
H
2
Cl
18
neat
2
Cl
19
1
2
1
R SR2
R SH + R X
o
30
100 C
16
Ph
30
1
2
3
Br
Scheme 2
conditions at various temperatures (Scheme 1). As
revealed in Table 1, the best result was obtained at 100 °C.
Therefore, we decided to perform our study at thiol:halide
at 1.1:1 at 100 °C to afford the corresponding sulfides in
moderate to excellent yields (Scheme 2). Representative
results are summarized in Table 2. The product isolation
with very high purity was easily achieved by subjecting the
crude reaction mixture to preparative TLC.
17
6 4
4-CH C H
20
65
3
Br
3
58
1
1
8
9
4-ClC
6
H
4
19
19
Br
31
52
1
Ph
Br
A series of thiols (both aromatic and aliphatic) were
treated with various halides to afford the corresponding
sulfides. The best results were obtained from the reaction
of aromatic thiols and benzyl halides. Benzyl sulfides
prepared from aromatic thiols (entries 1–6 and 12–15,
Table 2) generally give higher yields than those produced
from aliphatic thiols (entries 7–11, Table 2). Comparing
the reactions between thiols and benzyl chloride (entries 14
and 15, Table 2) with those of benzyl bromide (entries 4
and 5, Table 2) clearly shows longer reaction times and
lower yields for benzyl chloride. In the case of the reaction
of aliphatic thiols of increasing chain length, e.g., butane,
hexane, and octane (entries 9–11, Table 2), the yield of
the product increases with the increase in the length of the
alkyl chain. This may be attributed to the increase in the
electron-releasing capacity—and hence nucleophilicity—
with increasing length of the chain. In general, compared to
aromatic thiols, aliphatic thiols gave lower yields (entries
2
0
1
Ph
CH
3
(CH
2
)
4
CH
2
Br 40
–
2
4-CH
3
C
H
6 4
40
-
CH CHCH CH
3
3
2
Br
a
1
Yields refer to those of pure isolated products characterized by H
1
3
and C NMR spectroscopy
b
References for known compounds
primary and secondary aliphatic halides do not react with
thiols and remain mostly intact after the typical reaction
times (entries 20 and 21, Table 2).
In summary, we have developed a simple and efficient
procedure for preparation of sulfides. This solvent- and
catalyst-free reaction is very useful both from economical
and environmental points of view. This protocol offers
some advantages over procedures reported earlier in that it
avoids the use of hazardous organic solvents, toxic and
7
–11, Table 2). While treatment of thiols with 1-adaman-
tyl-, t-butyl, and allyl bromide gives the corresponding
sulfides in moderate yields (entries 16–19, Table 2),
1
23

Synthesis of sulfides under solvent- and catalyst-free conditions
411
expensive reagents, as well as operational simplicity, high
yields of products, and low costs.
4. Varma RS, Saini RK (1997) Tetrahedron Lett 38:4337
5
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1
8
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Chemicals were purchased from Merck chemical company.
13
1
Yields refer to isolated products. H (300 MHz) and
C
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1
1
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Typical procedure exemplified by the preparation
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1
1
3 12
50
1
In a typical experiment, a mixture of thiophenol (1.1 mmol,
21 mg) and benzyl bromide (1.0 mmol, 171 mg) was
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1
1
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magnetically stirred in a test tube at 100 °C for 16 h. After
completion of the reaction, as indicated by TLC, the crude
mixture was cooled and subjected to preparative TLC (silica
gel, eluent n-hexane) to obtain 191 mg of the pure benzyl
1
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phenyl sulfide (96%) as colorless crystals. M.p.: 41–42.5 8C
2
2
0. Wu J, Xia H-G (2005) Green Chem 7:708
1. Movassagh B, Sobhani S, Kheirdoush F, Fadaei Z (2003) Synth
Commun 33:3103
1
(
lit. [26] 41–42 8C). H NMR (CDCl ): d = 4.17 (s, 2H,
3
1
CH ), 7.22–7.38 (m, 10H, Ph) ppm; C NMR (CDCl3):
3
2
d = 39.0, 126.3, 127.2, 128.5, 128.9, 129.8, 136.4,
22. Movassagh B, Shaygan P (2006) ARKIVOC 7:130
2
2
2
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1
37.5 ppm [27–31].
This procedure is followed for all the reactions listed in
Table 2. All products are known compounds and were
26. Movassagh B, Mossadegh A (2004) Synth Commun 34:1685
27. Weinstein AH, Pierson RM (1958) J Org Chem 23:554
1
13
identified by spectroscopic data ( H and C NMR) that are
in good agreement with those reported (references in
Table 2).
2
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3
9. Polshettiwar V, Kaushik MP (2005) Catalysis Commun 6:191
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Acknowledgments Financial support from K. N. Toosi University
of Technology Research Council and the Iranian National Science
Foundation (INSF) is gratefully acknowledged.
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123