Multicomponent reactions for the synthesis of functionalized 1,4-oxathiane-3-thiones under microwave irradiation in water

Article abstract of DOI:10.1016/j.cclet.2013.03.003

A series of substituted 1,4-oxathiane-3-thione derivatives were synthesized via one-pot multicomponent reactions of nitromethane, carbon disulfide and oxiranes in the presence of Et₃N in water as the solvent under microwave irradiation. Particularly valuable features of this method include high yields of products, broad substrate scope, short reaction time and straightforward procedure.

Full text of DOI:10.1016/j.cclet.2013.03.003

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Chinese Chemical Letters xxx (2013) xxx–xxx
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Chinese Chemical Letters
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Original article
Multicomponent reactions for the synthesis of functionalized 1,4-oxathiane-3-
thiones under microwave irradiation in water
b
a
c
Zinatossadat Hossaini a, , Faramarz Rostami-Charati , Samereh Seyfi , Mehdi Ghambarian
*
a Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran
b Department of Chemistry, Facualty of Science, Gonbad Kavous University, P.O. Box 163, Gonbad, Iran
c Department of Chemistry, Karaj Branch, Islamic Azad University, Karaj, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
A series of substituted 1,4-oxathiane-3-thione derivatives were synthesized via one-pot multicompo-
nent reactions of nitromethane, carbon disulfide and oxiranes in the presence of Et3N in water as the
solvent under microwave irradiation. Particularly valuable features of this method include high yields of
products, broad substrate scope, short reaction time and straightforward procedure.
ß 2013 Zinatossadat Hossaini. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Received 21 January 2013
Received in revised form 2 February 2013
Accepted 20 February 2013
Available online xxx
Keywords:
Oxirane
Nitromethane
Carbon disulfide
1,4-Oxathiane
Three-component reaction
1. Introduction
substituted oxiranes in the presence of Et3N [9]. As part of our
current studies on the development of new routes in heterocyclic
1,4-Oxathiane nucleus is the key structural motif present in
certain commercial systemic fungicides broadly used in agricul-
ture [1]. Organophosphorus derivatives of 1,4-oxathiane are
insecticidal and acaricidal [2]. Some other 1,4-oxathiane deriva-
tives have been found to exhibit activity against tumors, HIV [3],
candidosis, and aspergillosis [4]. Recently, the 1,4-oxathiane
synthesis, we report an efficient three component reaction
between nitromethane 1, carbon disulfide 2 and epoxide 3 in
water at 70 8C which constitutes a direct synthesis of function-
alized 1,4-oxathiane-3-thione 4 in 74%–85% yields (Table 1).
2. Experimental
nucleus has been reported as
a suitable substructure for
muscarinic agonists [5]. Epoxides are versatile intermediates in
organic synthesis mainly due to their susceptibility to a variety of
nucleophiles [6] and availability in optically pure forms [7].
Nucleophilic ring opening of epoxides has been extensively studied
but little work has been carried out on the epoxide ring expansion
with nucleophiles [8], although it would offer useful synthetic
methods for various heterocycles. For example, only a few
attempts have been made for the synthesis of 1,4-oxathiane-2-
thiones via an epoxide ring-opening-ring-closing reaction cascade
and the results are not satisfactory in terms of yields, reaction
times, number of synthetic steps, and environmental consider-
ations. Recently reported the formation of novel functionalized
oxathiolanes from reaction between malononitrile, CS2 and
All chemicals used in this work were purchased from Fluka
(Buchs, Switzerland) and were used without further purification.
Melting points were measured on an Electrothermal 9100
apparatus. Elemental analyses for C, H, and N were performed
using a Heraeus CHN-O-Rapid analyzer. Mass spectra were
recorded on a FINNIGAN-MAT 8430 spectrometer operating at
an ionization potential of 70 eV. IR spectra were measured on a
Shimadzu IR-460 spectrometer. 1H NMR and 13C NMR spectra were
measured with a BRUKER DRX-500 AVANCE spectrometer at 500.1
and 125.8 MHz, respectively. NMR spectra were obtained for
solutions in CDCl3 using TMS as the internal standard or 85% H3PO4
as the external standard.
General procedure for preparation of compounds 4a–f: A solution
of the (0.11 g, 2 mmol) nitromethane 1 and triethyl amine
(2 mmol) in 10 mL of H2O was stirred for 30 min under microwave
conditions (In power of 800 W and T = 70 8C). Then, oxirane
(2 mmol) was added and finally, CS2 (0.76 g, 10 mmol) was added
* Corresponding author.
E-mail address: zshossaini@yahoo.com (Z. Hossaini).
1001-8417/$ – see front matter ß 2013 Zinatossadat Hossaini. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.03.003
Please cite this article in press as: Z. Hossaini, et al., Multicomponent reactions for the synthesis of functionalized 1,4-oxathiane-3-
thiones under microwave irradiation in water, Chin. Chem. Lett. (2013), http://dx.doi.org/10.1016/j.cclet.2013.03.003

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Table 1
O
S
S
Reaction of nitromethane, carbon disulfide and oxiranes in the presence of Et3N.
O2N
R
3
3
S
S
O
O
Et3N, M.W.
S
1
2
+
O
S
CH3-NO2
1
+
S C S
2
+
O
R
S
Et3N
H2O, 70 oC, 2 h
R
S
NO2
3
R
4
R
6
5
4
.
Compound 4
Oxiran
Product
Yield (%)
78
Scheme 1. Proposed mechanism for the one-pot synthesis of compound 4.
a
O
S
S
Ph
(d, 3J = 6.2, CH), 3.42 (dd, 2J = 12.2, 3J = 6.2, CH). 13C NMR: 22.3 (2
Me), 39.0 (CH2), 70.1 (CH2), 72.4 (CH), 79.8 (CH), 95.0 (CH2), 206.0
(CS). EI-MS: 206 (M+, 15), 146 (54), 130 (47), 116 (68), 89 (100), 43
(62). Anal. Calcd. for C8H14O2S2 (206.31): C 46.57, H 6.84; found: C
46.6, H 6.9.
O
b
c
85
90
S
O
S
CH3
H3C
O
O
S
6-(Isopropoxymethyl)-1,4-oxathiane-3-thione (4e): Yield: 0.16 g
(87%). Pale yellow oil. IR (KBr): 1631, 1592, 1367, 1173, 1082. 1H
NMR: 1.77–1.82 (m, CH2), 1.93–1.99 (m, CH2), 2.00–2.19 (m, CH2),
2.19–2.23 (m, CH2), 3.27 (q, CH), 3.50 (q, CH), 3.51 (d, 3J = 6.2, CH),
3.53 (d, 3J = 6.2, CH). 13C NMR: 23.2 (CH2), 25.8 (CH2), 31.6 (CH2),
37.5 (CH2), 45.5 (CH), 82.1 (CH), 95.3 (CH2), 186.8 (CS). EI-MS: 188
(M+, 15), 112 (54), 105 (47), 98 (68), 89 (100), 75 (62). Anal. Calcd.
for C8H12OS2 (188.30): C 51.03, H 6.42; found: C 51.2, H 6.5.
6-(Allyloxymethyl)-1,4-oxathiane-3-thione (4f): Yield: 0.18 g
(90%). Pale yellow oil. IR (KBr): 1646, 1591, 1354, 1168, 1098.
1H NMR: 3.26 (dd, 2J = 12.5, 3J = 6.2, CH), 3.33 (dd, 2J = 12.5, 3J = 6.2,
CH), 3.39 (d, 3J = 6.2, CH), 3.46 (dd, 2J = 12.5, 3J = 6.2, CH), 3.56 (d,
3J = 6.2, CH), 3.59 (dd, 2J = 12.5, 3J = 6.2, CH), 3.62–3.83 (m, CH),
4.04 (d, 3J = 6.2, CH2), 5.23 (dd, 2J = 12.5, 3J = 6.2, CH), 5.24 (dd,
2J = 12.5, 3J = 6.2, CH), 5.33–5.89 (m, CH). 13C NMR: 35.6 (CH2), 72.2
(CH2), 74.4 (CH2), 83.3 (CH), 95.0 (CH2), 115.8 (CH2), 134.1 (CH),
229.7 (CS). EI-MS: 204 (M+, 10), 132 (25), 128 (20), 114 (22), 146
(60), 71 (100), 57 (62). Anal. Calcd. for C8H12O2S2 (204.30): C 47.03,
H 5.92; found: C 47.1, H 5.9.
O
S
CH2OPh
O
d
89
S
O
O
S
S
i-PrOCH2
O
e
f
87
90
S
O
O
O
O
S
CH2Oallyl
S
O
to the reaction mixture. After completion of the reaction [2 h; TLC
(AcOEt:hexane = 1:4) monitoring], the reaction mixture was
filtered and the solid residue was crystallized from ethyl acetate
to afford 4.
6-Phenyl-1,4-oxathiane-3-thione (4a): yield: 0.16 g (78%). Pale
yellow oil. IR (KBr): 1626, 1590, 1341, 1161, 1085. 1H NMR: 3.38
(dd, 2J = 11.1, 3J = 6.9, CH), 3.53 (dd, 2J = 11.1, 3J = 6.7, CH), 4.63 (d,
3J = 6.2, CH), 4.64 (d, 3J = 6.2, CH), 4.93 (t, 3J = 6.3, CH), 7.24 (t,
3J = 7.2, CH), 7.34 (t, 3J = 7.2, 2 CH), 7.49 (d, 3J = 7.3, 2 CH). 13C NMR:
44.8 (CH2), 85.7 (CH), 94.6 (CH2), 127.4 (2 CH), 127.8 (CH), 128.6 (2
CH), 141.0 (C), 229.7 (CS). EI-MS: 210 (M+, 15), 132 (100), 134 (80),
120 (66), 106 (64), 89 (85), 77 (84). Anal. Calcd. for C10H10OS2
(210.30): C 57.11, H 4.79; found: C 57.2, H 4.8.
3. Results and discussion
Three component reaction between nitromethane 1, carbon
disulfide 2 and epoxide 3 in water at 70 8C produce functionalized
1,4-oxathiane-3-thione 4 in 74%–85% yields (Table 1).
The structures of compounds 4 were assigned by IR, 1H NMR,
13C NMR and mass spectral data. For example, the 1H NMR
6-Methyl-1,4-oxathiane-3-thione (4b): Yield: 0.12 g (85%). Pale
yellow oil. IR (KBr): 1632, 1592, 1367, 1174, 1118. 1H NMR: 1.66 (d,
3J = 7.4, Me), 2.40 (dd, 2J = 12.1, 3J = 5.9, CH), 3.00 (dd, 2J = 12.1,
3J = 5.8, CH), 3.68 (d, 3J = 6.2, CH), 3.75 (d, 3J = 6.5, CH), 5.24–5.29
(m, CH). 13C NMR: 19.5 (Me), 44.2 (CH2), 73.4 (CH), 94.7 (CH2),
229.7 (CS). EI-MS: 148 (M+, 5), 131(60), 105 (85), 89 (33), 75 (35),
42 (100), 58 (54). Anal. Calcd. for C5H8OS2 (148.23): C 40.51, H
5.44; found: C 40.6, H 5.5.
6-(Phenoxymethyl)-1,4-oxathiane-3-thione (4c): Yield: 0.21 g
(90%). Pale yellow oil. IR (KBr): 1646, 1591, 1354, 1168, 1098.
1H NMR: 3.46 (dd, 2J = 11.8, 3J = 5.7, CH), 3.53 (dd, 2J = 11.8, 3J = 5.7,
CH), 4.29 (d, 3J = 6.4, CH), 4.36 (dd, 2J = 12.4, 3J = 5.5, CH), 4.46 (d,
3J = 6.5, CH), 4.53 (dd, 2J = 12.4, 3J = 6.5,CH), 5.28–5.33 (m, CH), 6.93
(d, 3J = 6.4, 2 CH), 7.05 (t, 3J = 7.5, CH), 7.27 (d, 3J = 7.5, 2 CH). 13C
NMR: 34.1 (CH2), 66.2 (CH2), 84.4 (CH), 95.0 (CH2), 114.4 (2 CH),
121.9 (CH), 129.6 (2 CH), 159.4 (C), 229.7 (CS). EI-MS: 240 (M+, 10),
164 (20), 146 (20), 150 (25), 103 (60), 89 (100), 77 (62). Anal. Calcd.
for C11H12O2S2 (240.33): C 54.97, H 5.03; found: C 54.9, H 5.1.
6-Cyclohexyl-1,4-oxathiane-3-thione (4d): Yield: 0.18 g (89%).
Pale yellow oil. IR (KBr): 1649, 1581, 1340, 1155, 1144. 1H NMR:
1.11 (d, 3J = 6.2, 2 Me), 3.32 (dd, 2J = 12.4, 3J = 5.7, CH), 3.42 (dd,
2J = 12.2, 3J = 5.5, CH), 3.46–3.50 (m, CH), 3.42 (dd, 2J = 12.4, 3J = 5.7,
CH), 4.76–4.77 (m, CH), 3.42 (d, 2J = 12.2, 3J = 5.5, CH), 3.42
spectrum of 4a exhibited signals for methine (
along with characteristic multiplets for the aromatic protons (
d 3.38–4.93) protons,
d
7.24–7.49). The 13C NMR spectrum of 4a exhibited 10 distinct
resonances which further confirmed the proposed structure. The IR
spectrum of 4a displayed characteristic C55S bands. The mass
spectra of 4a–f displayed the molecular ion peak at the appropriate
m/z. The 1H NMR and 13C NMR spectra of 4b–f were similar to those
for 4a except for the 1,4-oxathian moieties, which exhibited
characteristic resonances in appropriate regions of the spectrum.
Although the mechanistic details of the reaction are not known, a
plausible rationalization may be advanced to explain the product
formation. Presumably, the reaction starts with formation of the
intermediate 5, followed by addition of CS2 2 to generate 6.
Cyclization of this intermediates leads to 4 (Scheme 1).
4. Conclusion
In summary, we report a reaction involving nitromethane,
carbon disulfide and epoxide, which affords a new route to the
synthesis of functionalized 1,4-oxathiane-3-thione. The present
procedure has the advantage that, not only is the reaction
performed under neutral conditions, but also the reactants can
be mixed without any prior activation or modification.
Please cite this article in press as: Z. Hossaini, et al., Multicomponent reactions for the synthesis of functionalized 1,4-oxathiane-3-
thiones under microwave irradiation in water, Chin. Chem. Lett. (2013), http://dx.doi.org/10.1016/j.cclet.2013.03.003

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3
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Please cite this article in press as: Z. Hossaini, et al., Multicomponent reactions for the synthesis of functionalized 1,4-oxathiane-3-
thiones under microwave irradiation in water, Chin. Chem. Lett. (2013), http://dx.doi.org/10.1016/j.cclet.2013.03.003