Cyclic and linear amidine catalysts for the efficient synthesis of cyclic trithiocarbonates from carbon disulfide and episulfides under mild conditions

Article abstract of DOI:10.1016/j.tetlet.2018.03.041

Cyclic and linear amidines effectively catalyzed the reaction of carbon disulfide and episulfides under mild conditions, such as ordinary pressure and ambient temperature, to give the corresponding cyclic trithiocarbonates in high yields.

Full text of DOI:10.1016/j.tetlet.2018.03.041

Accepted Manuscript
Cyclic and linear amidine catalysts for the efficient synthesis of cyclic trithio-
carbonates from carbon disulfide and episulfides under mild conditions
Naoto Aoyagi, Takeshi Endo
PII:
S0040-4039(18)30355-1
https://doi.org/10.1016/j.tetlet.2018.03.041
TETL 49810
DOI:
Reference:
Tetrahedron Letters
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Received Date:
Revised Date:
Accepted Date:
9 January 2018
9 March 2018
15 March 2018
Please cite this article as: Aoyagi, N., Endo, T., Cyclic and linear amidine catalysts for the efficient synthesis of
cyclic trithiocarbonates from carbon disulfide and episulfides under mild conditions, Tetrahedron Letters (2018),
doi: https://doi.org/10.1016/j.tetlet.2018.03.041
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Cyclic and linear amidine catalysts for the
efficient synthesis of cyclic trithiocarbonates
from carbon disulfide and episulfides under
mild conditions
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Naoto Aoyagi, Takeshi Endo*

1
Tetrahedron Letters
Cyclic and linear amidine catalysts for the efficient synthesis of cyclic
trithiocarbonates from carbon disulfide and episulfides under mild conditions
Naoto Aoyagi, Takeshi Endo
Molecular Engineering Institute, Kindai University, 11-6 Kayanomori, Iizuka, Fukuoka 820-8555, Japan.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Cyclic and linear amidines effectively catalyzed the reaction of carbon disulfide and episulfides
under mild conditions, such as ordinary pressure and ambient temperature, to give the
corresponding cyclic trithiocarbonates in high yields.
2009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Cyclic amidine;
Linear amidine;
Carbon disulfide;
Episulfides;
Cyclic trithiocarbonates
corresponding cyclic trithiocarbonates with high selectivity.12
However, this reaction requires both high temperatures and long
Introduction
Cyclic trithiocarbonates are key materials for the synthesis of
tetrathiafulvalene sulfur-containing metal
derivatives,1
reaction times to obtain the cyclic trithiocarbonates in high yields.
During the course of our research on the synthesis of cyclic
trithiocarbonates using several basic catalysts, we found that
cyclic and linear amidines efficiently catalyzed the ring-
expansion addition of episulfides with CS2 (Fig. 1). Herein, we
report a novel and efficient method for the synthesis of cyclic
trithiocarbonates from episulfides and CS2 using catalytic
amounts of cyclic and linear amidines under mild conditions,
such as ordinary pressure and ambient temperature (Scheme 1).
complexes,2 crown thioethers,3 dithiocarbonimidates4 and
dithiocarbamates,5 which have recently attracted significant
attention. Additionally, cyclic trithiocarbonates are used as
reversible addition-fragmentation chain transfer (RAFT) agents,
in order to synthesize amphiphilic multiblock co-polymers6 and
hyperbranched-linking-hyperbranched polymers7 from vinyl
monomers. However, efficient methods for the synthesis of
cyclic trithiocarbonates are limited to only a few reports. One of
the most common processes is alkylation of the trithiocarbonate
anion with alkylene dihalides or alkylene dithiols in the presence
of a phase-transfer catalyst.8 This alkylation produces large
amounts of by-products such as alkali halides and/or alkali
trithiocarbonates because it requires excess amounts of carbon
disulfide (CS2) and bases. Another of the more simple processes
is the incorporation of CS2 into episulfides using catalytic
triethylamine9 or lithium tert-butoxide.10 However, the
triethylamine-catalyzed reaction requires high pressure and
moderate to high temperature in order to achieve high efficiency.
The lithium tert-butoxide-catalyzed reaction gives only moderate
yields of cyclic trithiocarbonates. On the other hand, the ring-
expansion addition of epoxides with CS2 (1.8-7.0 equiv.) in the
presence of a catalytic amount of the bimetallic aluminum(salen)
complex give mixtures of cyclic dithiocarbonates and cyclic
trithiocarbonates.11 We have previously reported that
isopropoxytitanatrane effectively catalyzed the reaction of cyclic
ethers (epoxide or oxetane) and CS2 (2 equiv.) to obtain the
———
Figure 1. Amidines and amines used in this study.
 Corresponding author. Tel.: +81-948-22-7210; fax: +81-948-21-9032; e-mail: tendo@moleng.fuk.kindai.ac.jp

2
Tetrahedron
shown by the result that the catalytic activity increased with
increasing basicity of the amino group, that is, amidine >
trialkylamine > nitrogen-containing aromatic heterocycle. A
plausible mechanism for the catalytic synthesis of cyclic
trithiocarbonates is shown in Scheme 2. Initially, the zwitterionic
dithiocarbamate is formed by nucleophilic attack of the nitrogen
atom of the amidine moiety onto the carbon atom of CS2, and
subsequent nucleophilic attack on the thiirane ring which leads to
the ring-opened alkyl trithiocarbonate anion. Finally, ring-closure
through elimination of the catalyst gives the cyclic
trithiocarbonate.
Scheme 1. Synthesis of cyclic trithiocarbonates from episulfides.
Results and Discussion
Table 2. Effect of the structures of the catalysts on the synthesis
of 3b in toluene under ambient conditions.a
First, we investigated the effect of the structures of the
catalysts on the ring-expansion addition of 2a and CS2 (2 equiv.)
in bulk at 1 atm and ambient temperature (Table 1). In a typical
experiment, CS2 (2 mmol) was added to the catalyst (0.01 mmol),
and the resulting mixture stirred at 25 °C. The colorless mixture
changed to an orange solution within a few seconds, and then a
blood red syrup gradually precipitated from the solution,
indicating formation of the zwitterionic dithiocarbamate. After
stirring for 10 minutes, 2a (1 mmol) was added to the reaction
mixture. The blood red syrup gradually dissolved, and then the
color of the mixture changed from pale orange to pale yellow.
The reaction was monitored by 1H NMR spectroscopy. As shown
in Table 1, strongly basic cyclic and linear amidines (1a, 1b and
1c) gave 3a in quantitative yields (Entries 1-3).13 In contrast,
moderately basic triethylamine (1d) afforded 3a in very low yield
(Entry 4), as suggested by the fact that the reaction of 2a and CS2
(5 equiv.) with 1d (10 mol%) required relatively severe
conditions such as 8000 kg/cm2 and 40 °C.9 The use of weakly
basic amines such as 1-methylimidazole (1e) and pyridine (1f)
resulted in almost no reaction under mild conditions (Entries 5
and 6), which indicates that the high basicity of the amidine
moiety is a prerequisite for catalysis.
Entry
Catalyst (pKa /-)b
Yield 3b (%)c
1
2
3
4
5
6
1a (13.42±0.20)
1b (13.28±0.20)
1c (12.53±0.20)
1d (10.62±0.25)
1e (7.01±0.1)
>99
97
>99
24
8
1f (5.23±0.1)
2
aReagents and conditions: 2b (1 mmol), CS2 (2 mmol), catalyst (0.01 mmol),
toluene (0.2 mL), 25 °C, 24 h.
bpKa values were obtained from SciFinder.14
cDetermined by 1H NMR spectroscopy.
Table 1. Effect of the structures of the catalysts on the
synthesis of 3a under ambient conditions without solvent.a
Entry
Catalyst (pKa /-)b
Yield 3a (%)c
1
2
3
4
5
6
1a (13.42±0.20)
1b (13.28±0.20)
1c (12.53±0.20)
1d (10.62±0.25)
1e (7.01±0.1)
>99
99
>99
18
3
1f (5.23±0.1)
<1
aReagents and conditions: 2a (1 mmol), CS2 (2 mmol), catalyst (0.01 mmol),
25 °C, 24 h.
bpKa values were obtained from SciFinder.14
Scheme 2. Plausible mechanism for the catalyzed synthesis of
cyclic trithiocarbonates from episulfides and CS2.
cDetermined by 1H NMR spectroscopy.
Furthermore, we examined the synthesis of various cyclic
trithiocarbonates from episulfides using 1a (1 mol%) at 1 atm
and 25 °C.16 The episulfides (2c-f) were synthesized by our
previous method.15 As shown in Table 3, the cyclic
trithiocarbonates (3a and 3b) were isolated in high yield (97%
and 98%) after short column chromatography on silica gel
(Entries 1 and 2). 2-(Methacryloyloxymethyl)thiirane (2c), 2-
(allyloxymethyl)thiirane (2d) and 2-(butoxymethyl)thiirane (2e)
containing electron withdrawing groups on the carbon atom next
Next, the ring-expansion addition of 2b with CS2 was carried
out in toluene for the synthesis of 3b as a solid product (Table 2).
The episulfide (2b) was synthesized by our previous method.15
As in the case of bulk conditions, cyclic and linear amidines (1a,
1b and 1c) also gave 3a in quantitative yields (Entries 1-3). The
use of 1d resulted in a remarkably decreased yield of 24%, and
the yield was decreased to less than 10% when 1e and 1f were
used as catalysts (Entries 4-6). The catalytic activity was affected
by the strongly basic amino group (pKa > 12) on the catalysts, as

3
Y.; Decurtins, S.; Meyer, G.; Gross, L. Nano Lett. 2014, 14,
3342-3346.
to the epoxy group were as reactive as 2b, and the corresponding
cyclic trithiocarbonates (3c, 3d and 3e) were isolated in high
yields (Entries 3-6). The episulfide containing a long-chain alkyl
group, 2-decylthiirane (2f), had a lower reactivity than the other
episulfides (Entry 7). When the reaction time was extended from
24 to 48 h, the conversion of 2f increased and the cyclic
trithiocarbonate (3f) was isolated in high yield (Entry 8).
2. (a) Adams, H.; Allott, C.; Bancroft, M. N.; Morris, M. J. J. Chem.
Soc., Dalton Trans. 2000, 4145-4153; (b) Nihei, M.; Kurihara, M.;
Mizutani, J.; Nishihara, H. J. Am. Chem. Soc. 2003, 125, 2964-
2973; (c) Brombacher, H.; Vahrenkamp, H. Inorg. Chem. 2004,
43, 6050-6053; (d) Lu, X. L.; Vittal, J. J.; Tiekink, E. R. T.; Goh,
L. Y.; Hor, T.S. A. J. Organomet. Chem. 2004, 689, 1444-1451;
(e) Alphonse, F.-A.; Karim, R.; C.-Soumillac, C.; Hebray, M.;
Collison, D.; Garner, C. D.; Joule, J. A. Tetrahedron 2005, 61,
11010-11019; (f) Okubo, T.; Maeda, R.; Kondo, M.; Mitani, T.;
Kitagawa, S. Chem. Lett. 2006, 35, 34-35; (g) Bertz, S. H.;
Moazami, Y.; Murphy, M. D.; Ogle, C. A.; Richter, J. D.;
Thomas, A. A. J. Am. Chem. Soc. 2010, 132, 9549-9551.
3. Ishii, A.; Asami, S.; Fujiwara, Y.; Ono, A.; Nakata, N.
Heteroatom Chem. 2011, 22, 388-396.
Table 3. Synthesis of various cyclic trithiocarbonates using 1a
under ambient conditions.a
4. Wang, B.; Yang, S.; Min, L.; Gu, Y.; Zhang, Y.; Wu, X.; Zhang,
L.; Elageed, E. H. M.; Wu, S.; Gao, G. Adv. Synth. Catal. 2014,
356, 3125-3134.
5. Lal, N.; Sarswat, A.; Kumar, L.; Nandikonda, K.; Jangir, S.; Bala,
V.; Sharma, V. L. J. Heterocyclic Chem. 2015, 52, 156-162.
6. Du, B.; Mei, A.; Yang, Y.; Zhang, Q.; Wang, Q.; Xu, J.; Fan, Z.
Polymer 2010, 51, 3493-3502.
7. Li, W.; Zhao, X.; Liu, H. Polym. Chem. 2014, 5, 1905-1911.
8. (a) Sugawara, A.; Sato, T.; Sato, R. Bull. Chem. Soc. Jpn. 1989,
62, 339-341; (b) Lee, A. M. W.; Chan, W. H.; Wong, H. C. Synth.
Commun. 1988, 18, 1531-1536.
9. Taguchi, Y.; Yanagiya, K.; Shibuya, I.; Suhara, Y. Bull. Chem.
Soc. Jpn. 1987, 60, 727-730.
10. Diebler, J.; Spannenberg, A.; Werner, T. Org. Biomol. Chem.
2016, 14, 7480-7489.
11. Clegg, W.; Harrington, R. W.; North, M.; Villuendas, P. J. Org.
Chem. 2010, 75, 6201-6207.
Entry
Episulfide
Solvent
Bulk
Time (h)
24
Yieldb (%)
99 (97)c
>99 (98)c
99 (92)c
>99 (99)c
89
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2e
2f
Toluene
Bulk
24
24
Bulk
24
Bulk
24
Bulk
36
>99 (97)c
12. Motokucho, S.; Takeuchi, D.; Sanda, F.; Endo, T. Tetrahedron
2001, 57, 7149-7152.
Bulk
24
69
13. Synthesis of 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine (1a): The
mixture of N-methyl-1,3-diaminopropane (4.41 g, 50 mmol) and
N,N-dimethylacetamide dimethyl acetal (90% purity, 7.77 g, 52.5
mmol) was stirred at 80 °C without solvent. After 1 h, the mixture
was evaporated in vacuo, and the residue was distilled under
reduced pressure to give 1a (5.33 g, 95%) as a colorless liquid;
B.p. 62-64 °C/1.0 kPa. 1H NMR (400 MHz, CDCl3, 25 ˚C) δ
(ppm): 1.83 (quin, J = 6.0 Hz, 2H, NCH2CH2CH2N), 1.96 (s, 3H,
CCH3), 2.88 (s, 3H, NCH3), 3.13 (t, J = 6.0 Hz, 2H,
8
2f
Bulk
48
>99 (98)c
a
Reagents and conditions: 2a-f (5 mmol), CS2 (10 mmol), 1a (0.05 mmol),
bulk or in toluene (1 mL), 25 °C, 24-48 h.
bDetermined by 1H NMR spectroscopy.
cIsolated yields are in parentheses.
Conclusion
NCH2CH2CH2NCH3), 3.29 (t, J = 6.0 Hz, 2H,
NCH2CH2CH2NCH3). 13C NMR (100 MHz, CDCl3, 25 ˚C) δ
(ppm): 22.0 (NCH2CH2CH2N), 22.7 (CCH3), 38.7 (NCH3), 44.2
(NCH2CH2CH2NCH3), 48.3 (NCH2CH2CH2NCH3), 155.8 (NCN).
14. The pKa values were calculated using Advanced Chemistry
Development (ACD/Labs) software V11.02 ((c)1994-2016
ACD/Labs).
We have demonstrated that cyclic and linear amidines
effectively catalyzed the reactions of CS2 and episulfides to
afford the corresponding cyclic trithiocarbonates in high yields
under mild conditions such as ordinary pressure and ambient
temperature. The catalytic activity is highly affected by the
strongly basic amino group on the catalysts; amidines efficiently
catalyze the trithiocarbonate-forming reaction, in contrast
triethylamine and heterocyclic aromatic compound such as 1-
methylimidazole and pyridine show low reactivity. We believe
that the results obtained in this study will serve as a basis for
creating a mild and simple method for the synthesis of cyclic
trithocarbonate-containing organic compounds.
15. Aoyagi, N.; Endo, T. ChemistrySelect 2017, 2, 4465-4467.
16. Typical procedure of cyclic trithiocarbonates (3a-f): A mixture of
CS2 (10 mmol) and 1a (0.05 mmol) was stirred at 25 °C for 10
min, and then episulfide (5 mmol) or a dilute solution of episulfide
in toluene (1 mL) was added dropwise to the mixture. After the
mixture was stirred at 25 °C for 24-48 h, the reaction mixture was
diluted with ethyl acetate (10 mL), and washed with water (10
mL). The aqueous phase was extracted with ethyl acetate (10 mL),
and the combined organic layers were dried over Na2SO4 and
evaporated in vacuo. The residue was purified by silica gel
column chromatography (hexane/acetone = 3:1) to give cyclic
trithiocarbonate as a yellow oil (3a, 3c-f) or solid (3b).
References and notes
1. (a) Gautier, N.; Dumur, F.; Lloveras, V.; V.-Gancedo, J.; Veciana,
J.; Rovira, C.; Hudhomme, P. Angew. Chem. Int. Ed. 2003, 42,
2765-2768; (b) Otón, F.; Pfattner, R.; Oxtoby, N. S.; M.-Torrent,
M.; Wurst, K.; Fontrodona, X.; Olivier, Y.; Cornil, J.; Veciana, J.;
Rovira, C. J. Org. Chem. 2011, 76, 154-163; (c) C.-Lacalle, D.;
Arumugam, S.; Elmasly, S. E. T.; Kanibolotsky, A. L.; Findlay, N.
J.; Inigo, A. R.; Skabara, P. J. J. Mater. Chem. 2012, 22, 11310-
11315; (d) Tucker, N. M.; Briseno, A. L.; Acton, O.; Yip, H.-L.;
Ma, H.; Jenekhe, S. A.; Xia, Y.; Jen, A. K.-Y. ACS Appl. Mater.
Interfaces 2013, 5, 2320-2324; (e) Schuler, B.; Liu, S.-X.; Geng,
Supplementary Material
Supplementary data (experimental data and NMR spectra of
isolated compounds) associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2018.xxx.

4
Tetrahedron
Highlights
⦁ Efficient synthesis of cyclic trithiocarbonates
from episulfides with CS2.
⦁ Cyclic and linear amidines had high catalytic
activity.
⦁ Cyclic trithiocarbonates were obtained in high
yields under mild conditions.