One-pot synthesis of symmetrical diaryl trithiocarbonates through copper-catalyzed coupling of aryl compounds, sodium sulfide, and carbon disulfide

Article abstract of DOI:10.1002/ejoc.201201126

In this study, a protocol for the synthesis of symmetrical diaryl trithiocarbonates through the one-pot copper-catalyzed coupling reaction of sodium sulfide, carbon disulfide, and aryl compounds in DMF solution is presented. This method allows the synthesis of symmetrical diaryl trithiocarbonates without the use of highly toxic thiophosgene, and also, commercially available aryl halides were used instead of less available, toxic thiols.

Full text of DOI:10.1002/ejoc.201201126

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201201126
One-Pot Synthesis of Symmetrical Diaryl Trithiocarbonates through Copper-
Catalyzed Coupling of Aryl Compounds, Sodium Sulfide, and Carbon Disulfide
Mohammad Gholinejad*[a]
Dedicated to Professor Carmen Nájera
Keywords: Sulfur / Copper / Arenes / Cross-coupling
In this study, a protocol for the synthesis of symmetrical diaryl
trithiocarbonates through the one-pot copper-catalyzed cou-
pling reaction of sodium sulfide, carbon disulfide, and aryl
compounds in DMF solution is presented. This method al-
lows the synthesis of symmetrical diaryl trithiocarbonates
without the use of highly toxic thiophosgene, and also, com-
mercially available aryl halides were used instead of less
available, toxic thiols.
This method is not very popular, as thiol compounds are
foul smelling and a limited number of aryl thiols are com-
mercially available. Also, thiophosgene is a highly toxic li-
quid that has been used as the chemical weapon known as
Lacrimite. The handling of this chemical needs precaution,
and protective equipment including rubber gloves, safety
goggles, and breathing equipment should be used.[14] Diaryl
trithiocarbonates have also been produced in very small
quantities, as byproducts, in the reaction of sodium iodide
with carbon disulfide and aryldiazonium fluoroborate in a
free-radical process.[15] Hence, the design and development
of a new strategy for the preparation of diaryl trithio-
carbonates seems to be of paramount importance.
Introduction
Carbon–sulfur bonds commonly occur in pharmaceuti-
cally and biologically active compounds.[1] Among the vari-
ety of sulfur compounds, trithiocarbonates are very impor-
tant because of their wide range of applications, which in-
clude their use as pharmaceutical agents and agrochemicals,
and they are also used as lubricating agents in oil addi-
tives.[2] In addition, trithiocarbonates are generally used as
reversible addition–fragmentation chain-transfer (RAFT)
agents in free-radical polymerization processes.[3]
The limited number of synthetic methods available for
the preparation of dialkyl trithiocarbonates involve reac-
tions of thiols with either thiophosgene or chlorodithio-
formates[4,5] and two-step reactions of thiols with carbon
disulfide and alkyl halides.[6] The dialkylation of the in situ
generated trithiocarbonate anion in the reaction of CS2
with Cs2CO3,[7] KF/Al2O3,[8] nBu4NOH,[9] K3PO4,[10] and
so forth[11] has also been reported. Recently, the one-pot
synthesis of trithiocarbonates from the reaction of 1,1Ј-
thiocarbonyl diimidazole with thiols and its application in
the controlled radical polymerization of vinyl monomers
was reported.[12] Moreover, the preparation of alkyl aryl tri-
thiocarbonates by reaction of bis(thiocarbonyl) disulfide
with azo compounds was reported.[13] However, a literature
search indicated that there is only one report on the synthe-
sis of symmetrical diaryl trithiocarbonates through the re-
action of thiophosgene with aryl thiols in basic media.[4]
Results and Discussion
In recent years, transition-metal catalysis has intensely
changed the face of modern organic chemistry by introduc-
ing a variety of novel synthetic methods. Carbon–hetero-
atom bond-formation reactions are one of the great
achievements of transition-metal-catalyzed reactions, and
C(aryl)–S bond formation by the direct coupling of aryl
halides and thiols or an in situ generated thiolate moiety[16]
has received wide attention.[17]
Herein, a novel protocol for the synthesis of symmetrical
diaryl trithiocarbonates through a copper-catalyzed one-
pot coupling reaction of carbon disulfide, sodium sulfide,
and aryl compounds in DMF at 100–130 °C is examined.
In preliminary experiments, the one-pot reaction of sodium
sulfide (1.1 mmol), carbon disulfide (5 mmol), and iodo-
benzene (2 mmol) as a model reaction was studied under
different reaction conditions by using various solvents such
as H2O, toluene, and DMF and also by using different cop-
[a] Department of Chemistry, Institute for Advanced Studies in
Basic Sciences (IASBS),
P. O. Box 45195-1159, Gava zang, Zanjan 45137-6731, Iran
Fax: +98-241-4214949
E-mail: gholinejad@iasbs.ac.ir
Homepage: http://www.iasbs.ac.ir/~gholinejad/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201126.
Eur. J. Org. Chem. 2013, 257–259
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
257

M. Gholinejad
SHORT COMMUNICATION
per sources such as CuI, CuCl, and CuSO4 in the presence ucts in 82–87% yield (Table 2, entries 9–12). In a previous
or absence of Et3N (Table 1).
report,[4] the preparation of diphenyl trithiocarbonates as
Table 1. Effects of solvent, copper catalyst, and base.
Table 2. One-pot synthesis of structurally different symmetrical di-
aryl trithiocarbonates by the copper-catalyzed coupling reactions
of aryl compounds, carbon disulfide, and sodium sulfide.
Entry Catalyst
Conditions[a] Solvent
Yield[b] [%]
1
2
3
4
5
6
7
8
CuCl
CuCl
CuI
CuI
CuI
CuSO4
CuSO4
CuI
–
CuI
A
A
A
A
A
A
A
B
DMF
toluene
H2O
toluene
DMF
H2O
DMF
DMF
DMF
DMF
DMF
67
trace
60
trace
81
43
65
80
0
20
9
10
11
C
D
E
CuI
15
[a] Conditions A: Na2S (1.1 mmol), CS2 (5 mmol), iodobenzene
(2 mmol), CuX (5 mol-%). Conditions B: Na2S (1.1 mmol), CS2
(5 mmol), iodobenzene (2 mmol), CuI (5 mol-%), Et3N (2.4 mmol).
Conditions C: Na2S (1.1 mmol), CS2 (5 mmol), iodobenzene
(2 mmol). Conditions D: CS2 (5 mmol), Cs2CO3 (1 mmol), iodo-
benzene (2 mmol), CuI (5 mol-%). Conditions E: K3PO4 (1 mmol),
CS2 (5 mmol), iodobenzene (2 mmol), CuI (5 mol-%). [b] Isolated
yield.
The results indicate that among the various copper
sources and solvents tested, CuI and DMF were the most
effective for this reaction (Table 1, entry 5). However, the
presence of Et3N did not show any significant effect on the
yield of the reaction (Table 1, entry 8).
In the absence of the catalyst, the reaction did not show
significant progress (Table 1, entry 9). For comparison, two
recently reported methods for the preparation of symmetri-
cal dialkyl trithiocarbonates were used for the copper-cata-
lyzed synthesis of symmetrical diaryl trithiocarbonates with
the use of CuI as the catalyst and DMF as the solvent at
100 °C. By employing CS2/Cs2CO3,[7] in the presence of CuI
and iodobenzene the corresponding diphenyl trithiocarbon-
ate was obtained in low yield (20%; Table 1, entry 10). Also,
in the case of K3PO4,[10] the diphenyl trithiocarbonate was
produced in 15% yield (Table 1, entry 11).
Subsequently, reactions of various aryl iodides such as
iodobenzene, 4-iodotoluene, 4-iodoanisole, 2-iodotoluene,
2-iodoanisole, 4-iodobenzonitrile, and 1-iodonaphthalene
were studied under the above-optimized conditions
(Table 2). The reactions proceeded well, and the corre-
sponding diaryl trithiocarbonates were obtained in high
yields. 2-Iodothiophene as a heterocyclic aryl iodide was
found to react successfully, and the desire trithiocarbonate
was produced in 85% yield (Table 2, entry 4). Also, 4-
bromonitrobenzene and 4-bromobenzonitrile as active
bromoaryl substrates gave the desired trithiocarbonates in
62 and 70% yield, respectively (Table 2, entries 7 and 8).
Phenolic derivatives such as phenyl tosylate, phenyl triflate,
4-nitrophenyl triflate and 4-nitrophenyl tosylate were also
found to react smoothly to afford the corresponding prod- [a] Isolated yield.
258
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Eur. J. Org. Chem. 2013, 257–259

One-Pot Synthesis of Symmetrical Diaryl Trithiocarbonates
the sole compound was demonstrated. Notably, the 1H
NMR spectra of the products and those of their diaryl sulf-
ide analogues are similar, but the protons of the diaryl tri-
thiocarbonates are shifted upfield relative to the protons of
the diaryl sulfides (see the Supporting Information).
To probe the scope of the presented protocol for the one-
pot synthesis of unsymmetrical diaryl and alkyl aryl tri-
thiocarbonates, the reaction of iodobenzene in the presence
of 1-iodo-4-nitrobenzene and the reaction of iodobenzene
in the presence of n-butyl bromide were studied. The results
show that in both cases symmetrical diaryl trithiocarbon-
ates and dialkyl trithiocarbonates were formed; the forma-
tion of unsymmetrical alkyl aryl trithiocarbonates was not
observed.
The utility of this system was further illustrated by the
flexibility of being able to scale up the reaction by using
20 mmol of iodobenzene, Na2S (11 mmol), CS2 (50 mmol),
and CuI (5 mol-%) at 100 °C. The reaction was performed
with success within an appropriate reaction time and af-
forded the corresponding phenyl trithiocarbonate in 75%
yield.
der grant no. G2012IASBS156). The author is also thankful to
Professor Habib Firouzabadi for helpful comments and Professor
Babak Karimi for providing facilities, including the chemicals used
throughout this study.
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of symmetrical diaryl trithiocarbonate in a practical and
safe way was reported. The coupling of carbon disulfide,
sodium sulfide, and aryl compounds, including aryl iodides,
activated aryl bromides, and phenyl tosylate and/or triflate,
catalyzed by CuI provided the trithiocarbonates in one pot.
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Experimental Section
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General Procedure for the Synthesis of Diaryl Trithiocarbonates:
Na2S (1.1 mmol) powder was added to a stirring mixture of CS2
(5 mmol) and DMF (2 mL) at room temperature. After 15 min,
CuI (5 mol-%) and the aryl compound (2 mmol) were added to the
red-colored reaction mixture, which was stirred and heated at 100–
130 °C for the appropriate length of time. Then, the reaction mix-
ture was cooled to room temperature and extracted with EtOAc.
Evaporation of the solvent yielded the crude diaryl trithiocarbon-
ate, which was purified by flash column chromatography on silica
gel (EtOAc/n-hexane).
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Supporting Information (see footnote on the first page of this arti-
1
cle): Characterization data, copies of the H NMR and 13C NMR
spectra, HRMS data, and FTIR spectra of the products.
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Acknowledgments
The author gratefully acknowledges support of the Institute for
Advanced Studies in Basic Sciences (IASBS) Research Council (un-
Received: August 17, 2012
Published Online: November 26, 2012
Eur. J. Org. Chem. 2013, 257–259
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
259