A convenient one-pot method for the synthesis of symmetrical dialkyl trithiocarbonates using NH4OAc under mild neutral conditions

Article abstract of DOI:10.1002/jccs.201800062

A facial, new, one-pot method for the preparation of symmetrical organic trithiocarbonates from various alkyl halides and carbon disulfide is described. This is a convenient, clean, and mild procedure, which involves the use of the neutral, nontoxic, commercially available, and inexpensive reagent NH₄OAc in the preparation of the trithiocarbonate ion from carbon disulfide.

Full text of DOI:10.1002/jccs.201800062

Received: 17 February 2018
DOI: 10.1002/jccs.201800062
Revised: 25 July 2018
Accepted: 20 September 2018
A R T I C L E
A convenient one-pot method for the synthesis of symmetrical
dialkyl trithiocarbonates using NH4OAc under mild neutral
conditions
Zeinab Arzehgar | Hosna Ahmadi
Department of Chemistry, Ilam University,
A facial, new, one-pot method for the preparation of symmetrical organic trithio-
Ilam, Iran
carbonates from various alkyl halides and carbon disulfide is described. This is a
Correspondence
Zeinab Arzehgar, Department of Chemistry, Ilam
convenient, clean, and mild procedure, which involves the use of the neutral, non-
toxic, commercially available, and inexpensive reagent NH4OAc in the preparation
of the trithiocarbonate ion from carbon disulfide.
University, Ilam, Iran.
Email: arzehgar@yahoo.com
Funding information
Ilam University Research Council
KEYWORDS
ammonium acetate, carbon disulfide, one-pot, neutral conditions,
trithiocarbonates
carbon disulfide under basic conditions. Many common bases
such as NAOH,[17] KOH,[18] NH4OH,[19] basic Al2O3,[20]
CS2CO3,[21] KF/Al2O3,[22] N-Bu4NOH,[23] K3PO4,[24] KOH/
TBAB/Al2O3,[25] K2CO3,[26] anion exchange resin,[27]
copper-catalyzed coupling reaction,[28] and KI-tetraethylene
glycol complex[29] are employed in the in situ preparation of
the CS32− ion from carbon disulfide. However, most of these
methods require the use of expensive and strong bases and
long reaction times. One of the most powerful and new
approaches to improve the synthesis of organic compounds
involves the use of neutral reagents and mild reaction condi-
tions. Therefore, there is still attention paid in developing new
methods that would produce the desirable symmetrical trithio-
carbonates in high yields in the presence of neutral and inex-
pensive bases. In this regard, and in continuation of our
recent report on symmetrical trithiocarbonate synthesis in the
presence of KF/Al2O3,[22] N-Bu4NOH,[23] and imidazole,[30]
we report here an efficient and simple method for the synthe-
sis of symmetrical dialkyl trithiocarbonates in the presence of
ammonium acetate (NH4OAc).
1
| INTRODUCTION
One of the main efforts of researchers in organic chemistry
is directed toward the synthesis of compounds that include
sulfur bonds.[1] Among these compounds, trithiocarbonates
have been known as an important class having significant
applications; for instance, they act as inhibitors in the treat-
ment of cancer,[2] as pesticides and insecticides in agricul-
ture, as lubricating additives, and as intermediates and
synthons in organic synthesis.[3–5] These compounds have
been also employed as chain transfer agents for the revers-
ible addition fragmentation chain transfer (RAFT) in free-
radical polymerization.[6,7] Recently, Chang and co-workers
have reported a kind of vinylene trithiocarbonate (VTC) as
the electrolyte additive for the lithium ion.[8]
The classical routes for the synthesis of symmetrical
trithiocarbonates include (a) the reaction of thiols with
thiophosgene,[9,10] with chlorodithioformates,[11] or with car-
bon disulfide and alkyl halides[12,13]; (b) the reaction of
metal xanthates with epoxides[14] or episulfides[15]; and
(c) the reaction of the trithiocarbonate anion (CS32−) with
alkyl and aryl halides.[16]
This method was found to be effective and suitable from
the point of view of the green chemistry.[31] The use of metal
bases has several disadvantages such as their cost, toxicity,
and corrosive behavior. Also, the strong and basic reaction
The most convenient method for the preparation of the
trithiocarbonate anion is the in situ one-pot generation from
© 2018 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2018;1–4.
http://www.jccs.wiley-vch.de
1

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ARZEHGAR AND AHMADI
conditions that are employed, as well as the difficulty in
work-up during these reactions, are drawbacks. Therefore,
here we describe a new alternative approach to the one-pot
synthesis of symmetrical dialkyl trithiocarbonate from carbon
disulfide and alkyl halides using NH4OAc as an inexpensive,
effective, readily available, and mild neutral reagent.
SCHEME 2 Synthesis of symmetrical dialkyl trithiocarbonate by the
reaction of alkyl halides with carbon disulfide
yields (Table 2). However, the attempted reactions of aryl
halides and tertiary alkyl halides failed under the same con-
ditions, even after long reaction times (Table 2, entry 4).
Interestingly, a dialkyl trithiocarbonate containing an
ester functional group was synthesized well, without any
side products or changes in the functional group (Table 2,
entry 13).
Furthermore, the procedure's efficiency in the synthesis
of cyclic trithiocarbonates (1,3-dithiolane-2-thione) from
dihalides was examined (Scheme 3). Five-, six-, and seven-
membered cyclic trithiocarbonates were successfully pre-
pared with moderate yields without any by-product (Table 2,
entries 14–16).
2
| RESULTS AND DISCUSSION
To explore the optimal reaction conditions with respect to the
solvent, reaction times, and the amount of NH4OAc to be
used, the reaction of benzyl chloride (2.0 mmol) and carbon
disulfide (6.0 mmol) in the presence of NH4OAc at room tem-
perature was chosen as a model reaction (Scheme 1).
Initially, several solvents such as H2O, DMF, DMSO,
PEG, THF, and toluene as well as under solvent-free condi-
tion were examined at room temperature. According the
results shown in Table 1, DMSO was found to be the most
effective solvent for the progress of the reaction (Table 1,
entry 5).
In the next step, the effect of the amount of NH4OAc was
examined. The progress of the reaction depended on the
amount of NH4OAc; the reaction was found to be completed
in the presence of 3.25 equiv. of this reagent (94%), whereas
in the presence of 1.75 and 2 equiv., the yield was less (89%).
Eventually, a large number of symmetrical dialkyl
trithiocarbonate were synthesized by the reaction of alkyl
halides with carbon disulfide in the presence of NH4OAc at
room temperature with excellent yields under air atmosphere
and optimized reaction conditions (Scheme 2). The results
are summarized in Table 3.[25,32–34]
However, the exact mechanism of this protocol is not
2−
completely understood. In alkaline media, CS3 seems to
be produced by the self-condensation reaction of carbon
disulfide, according to the mechanism proposed in Scheme 4.
TABLE 2 Synthesis of the symmetric dialkyl trithiocarbonates under
optimized reaction conditions
Entry
1
RX
Time (hr)
Yield (%)a
BnCl
1.25
6
94
2
n-BuBr
90
3
s-BuBr
6
78
4
t-BuBr
6
No reaction
The procedure worked well with primary and secondary
alkyl, benzyl, and allyl halides to give the corresponding dia-
lkyl trithiocarbonates as the sole product in high to excellent
5
PhCH2CH2Br
PhCH2CH2CH2Br
CH2 = CHCH2Br
i-PrBr
5.5
6
90
6
91
7
4
86
8
6
74
9
MeI
3.5
1.25
6
52
10
11
12
13
14
15
16
EtI
80
PhBr
No reaction
(4-NO2)PhBr
BrCH2CO2Et
BrCH2CH2Br
BrCH2CH2CH2Br
BrCH2(CH2)2CH2Br
6
No reaction
SCHEME 1 Optimal reaction conditions
6
90
87
83
85
4
6.5
8
TABLE 1 Influence of the solvent on dibenzyl trithiocarbonate synthesis
in the presence of NH4OAc at room temperaturea
a
Entry
Solvent
H2O
Time (hr)
Yieldb (%)
No reaction
14
Isolated yield.
1
2
3
4
5
6
7
4
PEG
2.5
2.5
2.5
1.25
4
THF
19
DMF
43
DMSO
Toluene
Solvent-free
94
No reaction
No reaction
4
a
Reaction conditions: carbon disulfide (6.0 mmol), benzyl chloride (2.0 mmol),
ammonium acetate (6.5 mmol) in solvent (2 mL).
Isolated yield.
b
SCHEME 3 Synthesis of cyclic trithiocarbonates

ARZEHGAR AND AHMADI
3
TABLE 3 Symmetrical cyclic trithiocarbonates synthesis from alkyl
dihalides under optimized conditions
Entry
Alkyl Dihalide
Product
m = 1
Time (hr)
Yielda (%)
1
2
3
BrCH2CH2Br
4
87
83
85
BrCH2CH2CH2Br
BrCH2(CH2)2CH2Br
m = 2
6.5
8
m = 3
a
Isolated yield.
DMSO (2 mL) were added and the mixture was stirred vig-
orously at room temperature for 15 min. Then, 2.0 mmol
benzyl chloride (0.23 g) was added to the red-blood mixture,
whereupon it immediately changed to yellow. Then the mix-
ture was stirred for an appropriative time at room tempera-
ture (Table 2). The progress of the reaction was monitored
by thin-layer chromatography (TLC). Upon completion, the
reaction mixture was poured by preparative TLC (silica gel;
n-hexane) to afford the pure dibenzyl trithiocarbonate
(0.29 g, 94%) as a yellow oil.
Selected spectral data for representative trithiocarbonate:
Bis(3-phenylpropyl)trithiocarbonate: Table 2, entry 6:
yellow oil; 1H NMR (400 MHz, CDCl3): δ = 7.26–7.38 (m,
10 H), 3.4 (t, J = 7.4 Hz, 4 H), 2.79 (t, J = 7.6 Hz, 4 H),
2.1 (quin, J = 7.4 Hz, 4 H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 224.1, 140.9, 129.5, 126.2, 36.1, 34.9,
29.7 ppm.
Diethyl 2,20-(carbonothioyldisulfanediyl)diacetate: Table 2,
entry 13: Pale yellow oil; 1H NMR (400 MHz, CDCl3):
δ = 4.26 (q, J = 7.0 Hz, 4 H), 4.20 (s, 4 H), 1.32 (t,
J = 7.2 Hz, 6 H) ppm; 13C NMR (100 MHz, CDCl3):
δ = 220.3, 167.1, 62.2, 38.9, 14.1 ppm.
SCHEME 4 Possible mechanism for the synthesis of dialkyl
trithiocarbonate
In the mechanism proposed by Wertheim, however, trithio-
carbonate is obtained by the addition reaction of ammonium
sulfide with carbon disulfide.[19] The highly electrophilic
nature of carbon in CS2 and COS and the nucleophilicity of
S− will clearly favor the reaction, leading to the intermediate
1. The intermediates 1 and 2 are acidic and, in the presence
of a base, will give the stable trithiocarbonate ion, with the
concomitant release of bubbles of CO2.
1,3-Dithiolane-2-thione: Table 3, entry 1: yellow oil;
1
Yellow oil; H NMR (CDCl3, 400 MHz) δ = 3.98 (s, 4H);
13C NMR (CDCl3, 100 MHz) δ = 230.0, 45.1.
1,3-Dithiane-2-thione: Table 3, entry 2: yellow oil;1H
NMR (CDCl3, 400 MHz) δ = 3.23 (t, J = 1.6 Hz, 4H), 2.43
(m, 2H). 13C NMR (CDCl3, 100 MHz) δ = 222.0, 35.6, 21.6.
3
| CONCLUSIONS
In summary, we have developed a facile and new protocol for
the synthesis of symmetrical trithiocarbonates in the presence
of NH4OAc at room temperature under neutral and mild con-
ditions. This process is more economical and environmentally
friendly than previous methods because of the use of ammo-
nium acetate as a neutral and commercially available reagent
and the avoidance of expensive and/or dangerous and toxic
reagents. Additionally, high yields, simple procedure, rela-
tively short reaction times, easy work-up and handling, and
saving energy are some attractive features of this protocol.
ACKNOWLEDGMENT
This work was supported by the Ilam University Research
Council.
ORCID
Zeinab Arzehgar http://orcid.org/0000-0003-3774-4348
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SUPPORTING INFORMATION
Additional supporting information may be found online in
the Supporting Information section at the end of the article.
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How to cite this article: Arzehgar Z, Ahmadi H. A
convenient one-pot method for the synthesis of sym-
metrical dialkyl trithiocarbonates using NH4OAc
under mild neutral conditions. J Chin Chem Soc.
2018;1–4. https://doi.org/10.1002/jccs.201800062
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