Synthesis of cyclic di- and trithiocarbonates from epoxides and carbon disulfide catalyzed by N-heterocyclic carbene

Article abstract of DOI:10.1007/s11164-014-1634-5

The synthesis of cyclic di- and trithiocarbonates from the reaction of epoxides and carbon disulfide catalyzed by N-heterocyclic carbene prepared in situ is described. 1,3-Oxathiolane-2-thiones or 1,3-dithiolane-2-thiones was obtained in high yield with good selectivity when the reactions were carried out with 4 in DMSO at 100°C in the presence of K₂CO₃. The possible catalytic mechanism was proposed.

Full text of DOI:10.1007/s11164-014-1634-5

Res Chem Intermed
DOI 10.1007/s11164-014-1634-5
Synthesis of cyclic di- and trithiocarbonates
from epoxides and carbon disulfide catalyzed
by N-heterocyclic carbene
•
Jinsong Cao Meng Yu Hanzhu Li Liang Wang
•
•
•
•
•
•
Xu Zhu Guangying Wang Yanhui Shi
Changsheng Cao
Received: 27 December 2013 / Accepted: 23 March 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract The synthesis of cyclic di- and trithiocarbonates from the reaction of
epoxides and carbon disulfide catalyzed by N-heterocyclic carbene prepared in situ is
described. 1,3-Oxathiolane-2-thiones or 1,3-dithiolane-2-thiones was obtained in high
yield with good selectivity when the reactions were carried out with 4 in DMSO at
100 °C in the presence of K2CO3. The possible catalytic mechanism was proposed.
Keywords N-Heterocyclic carbene Á Carbon disulfide Á Epoxide Á
Dithiocarbonate Á Trithiocarbonate
Introduction
N-Heterocyclic carbenes (NHCs) have been investigated with great intensity in
recent years, and a large number of publications and reviews relating to NHC
complexes have been published [1–5]. NHCs usually serve as extremely strong r-
donor, and have been widely applied in catalysis [6–13]. We have preciously
reported that the combination of NHC prepared in situ with ZnBr2 catalyzes the
synthesis of cyclic carbonates in high yield from epoxides and carbon dioxide under
mild conditions (atmospheric pressure or even 0.05 MPa of CO2) [14].
Cyclic thiocarbonates have attracted much attention in material and biological
science. For example, dithiocarbonates are important compounds utilized for the
preparation of polymers [15, 16], and trithiocarbonates have been found to show
radio protective and insecticidal activity [17, 18]. The reaction between epoxides
Jinsong Cao and Meng Yu have contributed equally to this work.
J. Cao Á M. Yu Á H. Li Á L. Wang Á X. Zhu Á G. Wang Á Y. Shi (&) Á C. Cao (&)
School of Chemistry and Chemical Engineering and Jiangsu Key Laboratory of Green Synthetic
Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116, Jiangsu,
People’s Republic of China
e-mail: yhshi@jsnu.edu.cn
123

J. Cao et al.
and carbon disulfide is known to lead to a range of products, including
dithiocarbonates and trithiocarbonates [19, 20]. To extend the scope of reactions
catalyzed by NHC, it was decided to study the synthesis of di- and trithiocarbonate
from epoxides and carbon disulfide, and the results were reported herein.
Experimental
General procedures
Imidazol(in)ium chlorides were prepared using literature procedures [21, 22]. THF
and 1,4-dioxane were distilled from sodium benzophenone ketyl prior to use. DMF
˚
was stirred over MgSO4 overnight, filtered, and then distilled over 4 A molecular
˚
sieves. DMSO was distilled over calcium hydride and stored with 4 A molecular
sieves. All other reagents were commercially available and were used without
1
further purification. H NMR spectra were recorded on a Bruker DPX 400 MHz
1
spectrometer at room temperature and referenced to the residual H signals of the
solvent.
General procedure to synthesize 1,3-oxathiolane-2-thiones and 1,3-dithiolane-2-
thiones
An oven-dried 4 mL of vial with stir bar was charged with 4 (0.021 g, 0.05 mmol)
and K2CO3 (0.007 g, 0.05 mmol) in the glove box. The vial was capped and moved
out from the glove box, then epoxide (1 mmol), CS2 (3 mmol, 180 lL) and 2 mL of
DMSO were injected into the vial by syringe. The reaction was stirred at 80 °C for
48 h. After the reaction was cooled down, and 100 mL of water was added in the
reaction mixture. The organic layer was extracted with DCM (3 9 15 mL), and
dried by anhydrous Mg2SO4. The product was isolated by chromatography (eluent:
EtOAc/PE = 1:5).
Characterization data
Synthesis of compound 6 [24]
An oven-dried 4 mL of vial with stir bar was charged with 4 (0.021 g, 0.05 mmol)
and K2CO3 (0.007 g, 0.05 mmol) in the glove box. The vial was capped and moved
out from the glove box, then CS2 (0.5 mmol, 30 lL) and 2 mL of THF were injected
into the vial by syringe. The reaction was stirred at 80 °C for 24 h until a red solid
was formed and precipitated. The resulting mixture was filtered through a plug of
Celite, and washed by DCM. The volatiles were removed by rotavapor, and the
product was isolated by chromatography with DCM as eluent with 95 % yield.
Red solid (DCM), 1H NMR (400 MHz, CDCl3): d 7.34 (t, J = 7.6 Hz, 2H), 7.17
(d, J = 7.6 Hz, 4H), 3.51–3.45 (m, 4H), 1.39 (d, J = 6.4 Hz, 12H), 1.29 (d,
J = 6.8 Hz, 12H); 13C NMR (100 MHz, CDCl3): d 147.4, 130.6, 124.9, 113.2, 51.3,
29.3, 26.7, 23.7.
123

Synthesis of cyclic di- and trithiocarbonates
5-Ethyl-1,3-oxathiolane-2-thione (7a) [19] Yellow oil, 1H NMR (400 MHz,
CDCl3): d 5.08–5.01 (m, 1H), 3.58 (dd, J = 10.8 Hz, J = 6.4 Hz), 3.40 (t,
J = 9.6 Hz, 1H), 2.10–1.99 (m, 1H), 1.93–1.83 (m, 1H), 1.10 (t, J = 7.2 Hz, 1H);
13C NMR (100 MHz, CDCl3): d 212.1, 93.2, 39.4, 27.2, 10.2.
4-Ethyl-1,3-dithiolane-2-thione (7b) [19] Yellow oil, 1H NMR (400 MHz,
CDCl3): d 4.35–4.29 (m, 1H), 3.98 (dd, J = 12.0 Hz, J = 6.4 Hz, 1H), 3.71 (dd,
J = 12.0 Hz, J = 7.6 Hz, 1H), 2.03 (m, 2 H), 1.08 (t, J = 7.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d 227.9, 62.6, 48.0, 26.9, 12.7.
5-Butyl-1,3-oxathiolane-2-thione (8a) [19] Yellow oil, 1H NMR (400 MHz,
CDCl3): d 5.13–5.06 (m, 1H),3.58 (dd. J = 11.2 Hz, J = 6.8 Hz, 1H), 3.40 (t,
J = 9.6 Hz, 1H), 2.17 (s, 1H), 2.07–1.98 (m, 1H), 1.86-1.78 (m, 1H), 1.48–1.35 (m,
3H), 0.94 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 212.1, 91.8, 39.3,
33.4, 27.4, 22.3, 13.8.
4-Butyl-1,3-dithiolane-2-thione (8b) [19] Yellow oil, 1H NMR (400 MHz, CDCl3):
d 4.41–4.37 (m, 1H), 3.97 (dd, J = 11.6 Hz, J = 5.2 Hz, 1H), 3.71 (dd, J = 12.0 Hz,
J = 8.0 Hz, 1H), 1.98–1.88 (m, 2H), 1.34–1.31 (m, 4H), 0.93 (t, J = 6.8 Hz, 3H); 13
NMR (100 MHz, CDCl3): d 227.9, 60.9, 48.2, 33.2, 30.3, 22.4, 13.8.
C
5-Chloromethyl-1,3-oxathiolane-2-thione (9a) [19] Yellow oil, 1H NMR
(400 MHz, CDCl3): d 5.39–5.21 (m, 1H), 3.86 (d, J = 5.8 Hz, 2H), 3.76 (d,
J = 7.4 Hz, 1H), 3.70 (dd, J = 11.3 Hz, J = 7.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d 209.9, 88.4, 42.9, 37.3.
4-Chloromethyl-1,3-dithiolane-2-thione (9b) [19] Yellow oil, 1H NMR
(400 MHz, CDCl3): d 4.98–4.82 (m, 1H), 4.60 (t, J = 8.4 Hz, 1H), 4.42 (dd,
J = 9.2 Hz, J = 6.0 Hz, 1H), 3.75 (dd, J = 6.0 Hz, J = 2.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d 228.5, 78.4, 43.1, 33.8.
4-Phenyl-1,3-dithiolane-2-thione (10b) [19] Yellow crystal, mp 114–116 °C
(EtOAc/PE), 1H NMR (400 MHz, CDCl3): d 7.50–7.39 (m, 5H), 5.64 (dd, J = 9.6 Hz,
J = 10.0 Hz, 1H), 4.17 (t, J = 11.6 Hz, 1H), 4.03 (dd, J = 5.6 Hz, J = 12.0 Hz, 1H).
13C NMR (100 MHz, CDCl3): 227.2, 135.3, 129.3, 129.2, 127.5, 64.2, 49.8.
1
2-Thioxo-1,3-oxathiolan-5-yl)methyl benzoate (11a) [23] Yellow oil, H NMR
(400 MHz, CDCl3): d 8.04 (d, J = 7.2 Hz, 2H), 7.61 (t, J = 7.6 Hz, 1H), 7.47 (t,
J = 7.6 Hz, 2H), 4.70–4.63 (m, 3H), 4.21 (dd, J = 12.4 Hz, J = 4.4 Hz, 1H), 3.93
(dd, J = 12.0 Hz, J = 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 211.7, 165.8,
133.6, 129.7, 128.9, 128.5, 87.9, 68.6, 36.1.
5-(Benzyloxymethyl)-1,3-oxathiolane-2-thione (12a) [20] Yellow oil, 1H NMR
(400 MHz, CDCl3): d 7.39–7.31 (m, 5H), 4.59 (s, 2H), 4.48 (dd, J = 8.4 Hz,
J = 4.4 Hz, 1H), 4.07 (dd, J = 12.0 Hz, J = 5.6 Hz, 1H), 3.96 (dd, J = 12.0 Hz,
123

J. Cao et al.
J = 4.8 Hz, 1H), 3.86 (t, J = 9.6 Hz, 1H), 3.68 (dd, J = 9.6 Hz, J = 5.6 Hz, 1H). 13
C
NMR (100 MHz, CDCl3): d 211.9, 137.1, 128.5, 128.1, 127.8, 89.2, 73.7, 68.5, 36.1.
Results and discussion
Initially, the similar reaction conditions catalyzing the cycloaddition of epoxide
with CO2 [14] were tested for the reaction of epoxide with CS2. When the reaction
of 1,2-hexyleneoxide with carbon disulfide was carried out using 5 mol% of 4,5-
dihydro-1,3-bis(2,4,6-trimethylphenyl)-1H-imidazolinium chloride (2), ZnBr2, and
K2CO3 in DMSO at 80 °C for 48 h, 58 % of 5-butyl-1,3-oxathiolane-2-thione and
4-butyl-1,3-dithiolane-2-thione was obtained in 68:32 ratio (Table 1, entry 1).
However, it was found that Lewis acid has almost no effect on the yield and ratio of
Table 1 Screening of various of catalysts, solvents, bases, and Lewis acids for the cycloaddition reaction
of CS2 to 1,2-hexyleneoxide
S
S
O
O
S
cat., base
S
S
+
CS2
+
solvent, temp.
(a)
(b)
Entrya Cat. CS2 (eq.) Lewis acid Base
Solvent
Temp. (°C) Yield (%)b a:b ratio
1
2
2
2
1
3
4
5
4
4
4
4
4
4
4
4
4
4
4
4
3
ZnBr2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
80
80
80
80
80
80
80
80
80
80
80
80
80
80
50
100
80
80
80
58
60
60
85
78
90
92
83
50
45
73
80
88
91
70
20
0
68:32
70:30
70:30
40:60
66:34
77:23
52:48
60:40
65:35
70:30
14:86
62:38
75:25
66:34
70:30
60:40
–
2
3
AlCl3
3
3
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
4
3
5
3
6
3
7
3
8
3
Cs2CO3 DMSO
K3PO4 DMSO
tBuOK DMSO
9
3
10
11
12
13
14
15
16
17
18
19
a
3
1
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
1.5
4.5
6
3
3
3
3
THF
0
–
3
1,4-dioxane
0
–
Reaction conditions: the reaction was carried out in a 4 mL of vial containing 1,2-hexyleneoxide (127
lL, 1 mmol), CS2 (1–6 mmol), the catalyst (0.05 mmol), base (0.05 mmol) and solvent (2 mL) with or
without Lewis acid (0.05 mmol) at 50–100 °C for 48 h
b
Isolated yield with the average of two runs
123

Synthesis of cyclic di- and trithiocarbonates
the product (Table 1, entries 1–3). Therefore, no Lewis acid was added in further
reactions. Screening tests, using a series of imidazol(in)ium chlorides (1–5,
Scheme 1) with K2CO3 under the same conditions revealed that it seems that both
steric issues and electronic properties of NHC play important roles in the
cycloaddition (Table 1, entries 3–7). The best yield was attained by using
diisopropyl substituted unsaturated N-phenyl imidazolinium chloride 5; however,
its saturated analogues 4 gave the better selectivity of the product. The base also
affected the reaction (Table 1, entries 6, 8–10) and K2CO3 performed the best
among all the bases tested. The solvent also has an effect on the reaction (entries 6,
17–19). The reaction was conducted in DMF, THF, and 1,4-dioxane providing no
product, and the best solvent tested for the reaction is DMSO. To determine the
optimum reaction conditions, the amount of CS2 being used and reaction
temperature were also tested in the cycloaddition reaction of 1,2-hexyleneoxide
to CS2 (Table 1, entries 6, 11–16). The results showed that the higher yield and
better selectivity were obtained with 3 eq. of CS2 at 80 °C for 48 h. Therefore, in
the following studies, all the reactions were carried out with 5 mol% of 4 as
catalyst, K2CO3 as base, 3 eq. of CS2, and DMSO as a solvent at 80 °C for 48 h.
In order to better understand the reaction mechanism and determine the catalytic
active species, the zwitterionic NHC-CS2 adduct (6) (Scheme 2) was prepared and a
few control experiments were conducted (Table 2) with the cycloaddition of
hexyleneoxide to CS2.
It can be seen from the Table 2 that no product was observed with only either
imidazolinium chlorides 4 or base K2CO3 (Table 2, entries 1–2). The comparable
yield and selectivity of products was observed by using 4-CS2 adduct and 4 with
K2CO3, which suggests that the zwitterionic NHC-CS2 adduct is probably the
catalytic active species in the reaction.
To further probe the scope of the catalysis, a few selections of epoxides were
screened under the optimum conditions (Table 3). All the reactions gave good total
N
N
N
N
N
N
N
N
N
N
Cl
Cl
(4)
Cl
(5)
Cl
Cl
(1)
(2)
(3)
Scheme 1 Structure of imidazol(in)ium chlorides
CS2
THF
+
K2CO3
N
N
N
S
N
S
Cl
(4)
(6)
Scheme 2 Synthesis of NHC-CS2 adduct 6
123

J. Cao et al.
Table 2 The catalytic effect of different catalyst system on the reaction
S
S
S
O
O
S
S
cat.
3 CS2
+
+
DMSO, 80 oC, 48 h
(8a)
Yield (%)b
(8b)
Entrya
Catalytic system
8a:8b ratio
1
2
3
4
a
4
0
0
–
K2CO3
–
4, K2CO3
90
91
77:23
72:28
4-CS2 adduct
Reaction conditions: the reaction was carried out in a 4 mL of vial containing 1,2-hexyleneoxide (127
lL, 1 mmol), CS2 (180 lL, 3 mmol), the catalyst (0.05 mmol) and DMSO (2 mL) at 80 °C for 48 h
b
Isolated yield with the average of two runs
Table 3 Cycloaddition reaction of CS2 to epoxide
S
S
O
5 mol% 4, K2CO3
O
S
S
S
+
+
3 CS2
R
DMSO, 80 oC, 48 h
R
R
(a)
(b)
Entrya
R
Product
Yieldb
a:b ratio
1
2
3
4
5
6
a
Et
7a ? 7b
8a ? 8b
9a ? 9b
10b
92
90
93
95
89
86
75:25
77:23
70:30
\1:99
[99:1
[99:1
n-Bu
ClCH2
Ph
PhCOOCH2
PhCH2OCH2
11a
12a
Reaction conditions: the reaction was carried out in a 4 mL of vial containing epoxide (1 mmol), CS2
(180 lL, 3 mmol), 4 (0.021 g, 0.05 mmol), K2CO3 (0.007 g, 0.05 mmol) and DMSO (2 mL) at 80 °C for
48 h
b
Isolated yield with the average of two runs
yield of dithiocarbonates and trithiocarbonates (over 85 %). Interestingly, the
reactions with alkyl substituted epoxides preferred dithiocarbonates over trithio-
carbonates, and it is worth mentioning that only dithiocarbonates were achieved
with oxiran-2-ylmethyl benzoate and 2-(benzyloxymethyl)oxirane as starting
materials. However, the reaction with phenyl substituted epoxides gave only
trithiocarbonates as the product in good yield.
Based on previous reports and our study, we proposed the possible mechanism of
the cycloaddition reaction shown in Scheme 3. The possible nucleophile (Nu) in the
catalytic cycle would be the base carbonate ion.
123

Synthesis of cyclic di- and trithiocarbonates
S
S
S
N
S
N
O
Ar
Ar
b
R
R
SH
CS2
N
S
N
S
Ar
Ar
N
N
N
S
N
Ar
Ar
Ar
Ar
S
N
N
S
Ar
Ar
R
O
R
N
S
N
Ar
Ar
SH
S
S
R
S
O
S
Nu
S
Nu
O
S
Nu
S
a
R
O
S
O
R
Nu
R
Scheme 3 The mechanism of the cycloaddition reaction of CS2 and epoxide
In conclusion, we have demonstrated that NHC prepared in situ is a catalyst for
the cycloaddition of CS2 to epoxides. High conversions with good selectivity
towards cyclic thiocarbonates were achieved using NHC precursor, 4,5-dihydro-1,3-
bis(2, 6-diisopropylphenyl)-1H-imidazolinium chloride (4) with K2CO3 as base.
The catalytic active species was investigated and the possible mechanism was
proposed.
Acknowledgments We are grateful to the National Innovative Entrepreneurial Training Programs for
Undergraduates (12ssjcxzd02, HXKYZD201203 and 201310320047) of Jiangsu Normal University and
PAPD for financial support.
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