Efficient synthesis of ethyl 3-alkyl-4-oxo-2-thioxo-1,3-thiazolane-5- carboxylates from the reaction of carbon disulfide and primary amines in the presence of diethyl 2-chloromalonate

Article abstract of DOI:10.1007/s00706-008-0900-x

An efficient synthesis of ethyl 3-alkyl-4-oxo-2-thioxo-1,3-thiazolane-5- carboxylates via reaction of primary amines with CS₂ in the presence of diethyl 2-chloromalonate is described.

Full text of DOI:10.1007/s00706-008-0900-x

Monatsh Chem 139, 1029–1031 (2008)
DOI 10.1007/s00706-008-0900-x
Printed in The Netherlands
Efficient synthesis of ethyl 3-alkyl-4-oxo-2-thioxo-1,3-thiazolane-5-carboxylates
from the reaction of carbon disulfide and primary amines
in the presence of diethyl 2-chloromalonate
Issa Yavari1;2, Rahimeh Hajinasiri1, S. Zahra Sayyed-Alangi1, Nasir Iravani1
1
Chemistry Department, Science and Research Campus, Islamic Azad University, Ponak, Tehran, Iran
2
Chemistry Department, Tarbiat Modares University, Tehran, Iran
Received 9 January 2008; Accepted 22 January 2008; Published online 10 March 2008
# Springer-Verlag 2008
Abstract An efficient synthesis of ethyl 3-alkyl-4-oxo-
2-thioxo-1,3-thiazolane-5-carboxylates via reaction of
primary amines with CS2 in the presence of diethyl
2-chloromalonate is described.
part of our current studies, on the development of new
routes in hetrocyclic synthesis, we report the synthe-
sis of 4-oxo-2-thioxo-1,3-thiazolane-5-carboxylates.
Keywords Dithiocarbamates; 1,3-Thiazolane; Alkylamines;
Carbon disulfide; Three-component reaction.
Results and discussion
The above three-component reaction of CS2 and
alkylamines 1 in the presence of diethyl 2-chloro-
malonate (2) proceeds smoothly in MeCN at room
temperature to produce ethyl 3-alkyl-4-oxo-2-
thioxo-1,3-thiazolane-5-carboxylates 3, in good
yields (Scheme 1).
Introduction
Dithiocarbamates are bifunctional ligands which
have received attention due to their wide use as agro-
chemicals [1], pharmaceuticals [2], protecting group
in peptide synthesis [3], and chelatores in material
chemistry [4]. Organic dithiocarbamates are valuable
synthesis intermediates [5–8], which are ubiquitous-
ly found in a variety of biologically active com-
pounds [9, 10]. Functionalization of the carbamate
moiety offers an attractive method for the generation
of derivatives, which may constitute interesting me-
dicinal and biological properties [9, 10]. In fact, few
methods for the synthesis of dithiocarbamates have
been employed, and among them, reaction of amines
with costly and toxic reagents, such as thiophosgene
and isothiocyanates have been reported [11, 12]. As
The products were characterized based on their IR,
1H NMR, and 13C NMR. The mass spectra of com-
pounds 3a–3g displayed molecular ion peaks at ap-
propriate m=z values. The 1H NMR spectra of 3a–3g
exhibited characteristic AB and (AB)X3 spin sys-
tems for the NCH2 and OCH2 groups. The proton-
decoupled 13C NMR spectra of 3a–3g showed the
thiocarbonyl resonances at about ꢀ ¼ 187 ppm.
The following mechanism (Scheme 2) may be
invoked for the formation of compounds 3. Conceiv-
ably, the starting point of the reaction is the forma-
tion of a 1:1 adduct 4 between amine 1 and CS2,
which undergoes substitution reaction with 2 to pro-
duce 5. Intermediate 5 is converted to 3 by elimina-
tion of EtOH.
Correspondence: Issa Yavari, Chemistry Department, Tarbiat
Modares University, PO Box 14115-175, Tehran, Iran.
E-mail: yavarisa@modares.ac.ir
In conclusion, we report a novel transformation
involving carbon disulfide and alkyl amines in the

1030
I. Yavari et al.
The solvent was removed under reduced pressure and the
residue was purified by column chromatography (SiO2; n-
hexan:EtOAc¼ 3:1) to afford the pure title compounds.
Ethyl 3-benzyl-4-oxo-2-thioxo-1,3-thiazolane-5-carboxylate
(3a, C13H13NO3S2)
Dark yellow oil; yield: 0.47 g (80%); IR (KBr): ꢁꢀ¼ 1745,
1665, 1571, 1504, 1428 cmꢀ1; EI-MS: m=z (%) ¼ 295 (Mþ,
1
3
8), 222 (22), 219 (65), 91 (100); H NMR: ꢀ ¼ 1.26 (t, J ¼
7.1 Hz, Me), 4.27–4.31 (m, OCH2), 5.22 (AB q, ÁꢁAB
¼
22Hz, JAB ¼ 13.2Hz, NCH2), 5.40 (s, CH), 7.34–7.36 (m,
5CH)ppm; 13C NMR: ꢀ ¼ 13.7 (Me), 47.9 (NCH2), 52.8 (CH),
63.3 (OCH2), 128.1 (CH), 128.2 (CH), 128.8 (CH), 135.3 (C),
165.2 (C¼O), 171.3 (C¼O), 186.9 (C¼S) ppm.
Scheme 1
Ethyl 3-(4-chlorobenzyl)-4-oxo-2-thioxo-1,3-thiazolane-5-
carboxylate (3b, C13H12ClNO3S2)
Dark yellow oil; yield: 0.53 g (80%); IR (KBr): ꢁꢀ¼ 1739,
1636, 1575, 1545, 1461 cmꢀ1; EI-MS: m=z (%) ¼ 329 (Mþ,
5), 256 (22), 253 (67), 126 (100), 91 (39); 1H NMR: ꢀ ¼ 1.18
(t, 3J ¼ 7.2 Hz, Me), 4.12–4.17 (m, OCH2), 5.22 (AB q,
ÁꢁAB ¼ 15Hz, JAB ¼ 13.0Hz, NCH2), 5.36 (s, CH), 7.23 (d,
3J ¼ 8.8 Hz, 2CH), 7.42 (d, 3J ¼ 8.8Hz, 2CH) ppm; 13C NMR:
ꢀ ¼ 14.5 (Me), 46.3 (NCH2), 54.9 (CH), 59.98 (OCH2), 128.3
(CH), 130.8 (CH), 132.8 (C), 136.3 (C), 164.9 (C¼O), 165.5
(C¼O), 187.0 (C¼S) ppm.
Ethyl 3-(2-chlorobenzyl-4-oxo-2-thioxo-1,3-thiazolane-5-
carboxylate (3c, C13H12ClNO3S2)
Dark yellow oil; yield: 0.53 g (80%); IR (KBr): ꢁꢀ¼ 1747,
1630, 1587, 1521, 1453 cmꢀ1; EI-MS: m=z (%) ¼ 329 (Mþ,
7), 256 (22), 253 (72), 126 (100), 91 (61); 1H NMR: ꢀ ¼ 1.21
(t, 3J ¼ 7.2 Hz, Me), 4.02–4.07 (m, OCH2), 5.28 (AB q,
CH), 7.22 (m, 2CH), 7.41 (d, 3J ¼ 7.6 Hz, CH) ppm; 13C NMR:
ꢀ ¼ 14.5 (Me), 44.7 (CH), 55.0 (NCH2), 56.1 (OCH2), 127.1
(CH), 127.3 (CH), 128.4 (CH), 129.4 (CH), 130.1 (C), 132.4
(C), 164.7 (C¼O), 165.0 (C¼O), 186.4 (C¼S) ppm.
Scheme 2
presence of diethyl 2-chloromalonate, which affords
ethyl 3-alkyl-4-oxo-2-thioxo-1,3-thiazolane-5-car-
boxylates. The advantage of the present procedure
is that the reaction is performed under neutral con-
ditions by simple mixing of the starting materials.
The procedure described here provides an acceptable
one-pot method for the preparation of 4-oxo-2-
thioxo-1,3-thiazolanes.
3
ÁꢁAB ¼ 23Hz, JAB ¼ 12.1 Hz, NCH2), 6.75 (d, J ¼ 6.9 Hz,
Ethyl 3-(4-methoxybenzyl)-4-oxo-2-thioxo-1,3-thiazolane-5-
carboxylate (3d, C14H15NO4S2)
Dark yellow oil; yield: 0.48 g (75%); IR (KBr): ꢁꢀ¼ 1738,
1655, 1587, 1532, 1441 cmꢀ1; EI-MS: m=z (%) ¼ 325 (Mþ,
11), 252 (22), 249 (69), 122 (100), 91 (36); 1H NMR: ꢀ ¼ 1.19
Experimental
3
(t, J ¼ 7.2 Hz, Me), 3.52 (s, MeO), 4.12–4.18 (m, OCH2),
Carbon disulfide, 1, and 2 were obtained from Fluka and were
used without further purification. M.p.: Electrothermal-9100
apparatus. IR Spectra: Shimadzu IR-460 spectrometer. 1H and
13CNMR spectra: Bruker DRX-300 AVANCE instrument; in
CDCl3 at 300 and 75 MHz. EI-MS (70 eV): Finnigan-MAT-
8430 mass spectrometer. Elemental analyses (C, H, and N)
were performed with a Heraeus CHN-O-Rapid analyzer. The
results agreed favorably with the calculated values.
5.14 (AB q, ÁꢁAB ¼ 16 Hz, JAB ¼ 14.2 Hz, NCH2), 5.2 (s,
3
3
CH), 6.73 (d, J ¼ 8.3 Hz, 2CH), 7.39 (d, J ¼ 8.3 Hz, 2CH)
ppm; 13C NMR: ꢀ ¼ 14.4 (Me), 46.0 (NCH2), 54.0 (CH), 54.9
(MeO), 60.0 (OCH2), 113.6 (2CH), 129.4 (C), 130.5 (2CH),
159.4(C), 165.1 (C¼O), 165.7 (C¼O), 186.6 (C¼S) ppm.
Ethyl 3-(4-methylbenzyl)-4-oxo-2-thioxo-1,3-thiazolane-5-
carboxylate (3e, C14H15NO3S2)
General procedure for the preparation of compounds 3
To a stirred solution of 0.15g CS2 (2mmol) and 0.39 g 2
(2mmol) in 10 cm3 MeCN was added 2 mmol 1 at room
temperature. The reaction mixture was then stirred for 12h.
Dark yellow oil; yield: 0.48 g (75%); IR (KBr): ꢁꢀ¼ 1742,
1632, 1574, 1511, 1434 cmꢀ1; EI-MS: m=z (%) ¼ 309 (Mþ,
8), 236 (22), 233 (78), 106 (100), 91 (45); 1H NMR: ꢀ ¼ 1.19
(t, 3J ¼ 7.2 Hz, Me), 2.15 (s, Me), 4.10–4.16 (m, OCH2), 5.20

Ethyl 3-alkyl-4-oxo-2-thioxo-1,3-thiazolane-5-carboxylates
1031
(AB q, ÁꢁAB ¼ 18 Hz, JAB ¼ 13.9 Hz, NCH2), 5.20 (s, CH),
References
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3
6.90 (d, J ¼ 7.6 Hz, 2CH), 7.37 (d, J ¼ 7.6 Hz, 2CH) ppm;
13C NMR: ꢀ ¼ 14.5 (Me), 21.1 (Me), 46.7 (NCH2), 53.5 (CH),
60.5 (OCH2), 129.3 (CH), 129.4 (CH), 134.9 (C), 137.4 (C),
165.1 (C¼O), 165.7 (C¼O), 187.3 (C¼S) ppm.
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Yellow oil; yield: 0.48g (75%); IR (KBr): ꢁꢀ¼ 1737, 1630,
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