Solvent free one-pot synthesis of 2-thioxo-1,3-thiazinane-4-one derivatives

Article abstract of DOI:10.1080/10426507.2013.788002

An efficient one-pot synthesis of 2-thioxo-1,3-thiazinane-4-one derivatives through the reaction of primary amines and carbon disulfide in the presence of acryloyl chloride is described. This reaction is carried out under solvent-free condition and withou

Full text of DOI:10.1080/10426507.2013.788002

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Phosphorus, Sulfur, and Silicon and the Related
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SOLVENT FREE ONE-POT SYNTHESIS OF 2-THIOXO-1,3-
THIAZINANE-4-ONE DERIVATIVES
Farough Nasiri a , Amin Zolali b & Mohammad Ahmadiazar b
a Department of Applied Chemistry, Faculty of Science , University of MohagheghArdabili ,
P.O. Box 56199-11367, Ardabil , Iran
b Department of Chemistry, Faculty of Science , University of Kurdistan , Sanandaj , Iran
Accepted author version posted online: 03 Jun 2013.
To cite this article: Phosphorus, Sulfur, and Silicon and the Related Elements (2013): SOLVENT FREE ONE-POT SYNTHESIS
OF 2-THIOXO-1,3-THIAZINANE-4-ONE DERIVATIVES, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2013.788002
To link to this article: http://dx.doi.org/10.1080/10426507.2013.788002
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SOLVENT FREE ONE-POT SYNTHESIS OF 2-THIOXO-1,3-THIAZINANE-4-ONE
DERIVATIVES
Farough Nasiri,*1 Amin Zolali,2 Mohammad Ahmadiazar2
1Department of Applied Chemistry, Faculty of Science, University of MohagheghArdabili, P.O.
Box 56199-11367, Ardabil, Iran, E-mail: nasiri@uma.ac.ir
2Department of Chemistry, Faculty of Science, University of Kurdistan, Sanandaj, Iran
S
S
C
S
O
R
O
Solvent-free
r.t., 15 min
N
S
R NH2
+
+
Cl
Abstract An efficient one-pot synthesis of 2-thioxo-1,3-thiazinane-4-one
derivatives through the reaction of primary amines and carbon disulfide in
the presence of acryloyl chloride is described. This reaction is carried out
under solvent-free condition and without any catalyst at room temperature
within 15 min. The structures of products were deduced from their elemental
analysis and IR, 1H NMR, and 13C NMR spectroscopy, and mass
spectrometric
data.
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Kywords: carbon disulfide; primary amines; acryloyl chloride; nucleophilic
addition
INTRODUCTION
One of the major challenging areas of organic chemistry is to develop new processes that
are not only efficient, selective and high yielding but also environmentally benign. An efficient
approach to this goal is to carry out reactions under solvent-free conditions.1-3 Some advantages
of these processes are reduced reaction times, cost savings, a large reduction in reactor size and
decreased energy consumption. Dithiocarbamates are bifunctional ligands which are interesting
due to their numerous applications and their biological activities.4-7 An effective method for the
generation of new compounds which have interesting biological and pharmaceutical properties is
functionalization of the carbamate moiety.8 One of the important multitude of dithiocarbamates
is 2-thioxo-1,3-thiazinane-4-one derivatives and there are a few methods for synthesis of these
compounds in literature.9-14 The reported methods for the synthesis of these compounds require
multiple-steps and the reactions usually were carried out under harsh conditions and were time
consuming with low yields. For example, one route for the synthesis of 3a is cyclization of β-(N-
propylthiocarbamoylthio)propionic acid with phosphorus trichloride,9 or another route for
synthesis of compounds 3e, 3f is the reaction of α,β-unsaturated acid chlorides with N-
monosubstituted dithiocarbamic acid salts in dry diethyl ether, but these routes require
multisteps, harsh conditions and the yield of the reactions were only 47-62%.9,12 Recently
reaction between primary amines and carbon disulfide in the presence of fumaryl chloride has
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been reported to produce 2-(3-alkyl-4-oxo-2-thioxo-1,3-thiazolan-5-yl)acetic acid derivatives.15
Herein we report an efficient one pot and solvent free synthesis of 2-thioxo-1,3-thiazinane-4-one
derivatives from the reaction of primary amines and carbon disulfide in the presence of acryloyl
chloride. This reaction is carried out at room temperature under solvent-free condition and
completed within 15 min.
RESULTS AND DISCUSSION
The one-pot reaction of CS2 and primary amines 1 in the presence of acryloyl chloride 2
proceeds smoothly at room temperature under solvent free condition to generate 2-thioxo-1,3-
thiazinane-4-ones 3, in high yields (Scheme 1 and Table 1).
The structures of compounds 3a, 3b, 3e, and 3f were deduced by spectroscopic analysis
and comparison of their physical data with those reported in the literature.9-13 The structures of
1
other products were deduced from their elemental analysis and IR, H NMR, and 13C NMR
spectroscopy, and mass spectrometric data. The 1H NMR spectrum of 3c (CDCl3) exhibited two
multiplets (δ 3.08-3.12 and 3.17-3.22 ppm) identified as two six-membered ring methylene
protons and two triplets (δ 3.92 and 4.69 ppm, J = 5.5 Hz) identified as two outer methylene
protons. The OH proton of 3c appears as a broad peak at 2.12 ppm. The 1H decoupled 13C NMR
spectrum of 3c showed 6 distinct signals in agreement with the proposed structure. The mass
spectra of 3c showed molecular ion peak at appropriate m/z value.
Although the mechanism of the mentioned reaction is unknown, a possible mechanism
for this reaction is proposed in Scheme 2. The reaction starts by the addition of the amine to
carbon disulfide to form alkyl ammonium dithiocarbamate salt 4,14-19 which subsequently attacks
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to acryloyl chloride as a Michael-type addition to produce acyclic dithiocarbamate 5. This
intermediate undergoes cyclization to generate compounds 3.
CONCLUSION
In conclusion, the present reaction between primary amines and carbon disulfide in the
presence of acryloyl chloride provide simple and efficient entry in to synthesis of 2-thioxo-1,3-
thiazinane-4-one derivatives of potential synthetic interest. This procedure has advantages of
good yields, mild and safe reaction conditions.
EXPERIMENTAL
Melting points were measured with an Electrothermal 9100 apparatus. Elemental
analyses C, H, and N were performed using a Heraeus CHN-O-Rapid analyzer. IR spectra were
measured with a Shimadzu IR-460 spectrometer. NMR spectra were recorded with a Bruker
1
AVANCE-250 and 300 instruments (250.1 and 300.1 MHz for H and 62.5 and 75.5 MHz for
13C) with CDCl3 as solvent. Mass spectra were recorded with an Agilent-5975 C inert XL MSD
mass spectrometer operating at an ionization potential of 70 eV. Amines, acryloyl chloride and
carbon disulfide were obtained from Fluka (Buchs, Switzerland) and were used without further
purification. Sample 1H and 13C NMR spectra for 3a, 3g and 3i are presented in the Supplemental
Materials (Figures S 1 – S 6)
General procedure
To a stirred mixture of amine 1 (3 mmol) and carbon disulfide (0.15 g, 2 mmol) was
added acryloyl chloride (0.18 g, 2 mmol) at room temperature. The reaction mixture was then
stirred for 15 min. After completion the reaction mixture was purified by column
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chromatography over silica gel (Merck 230–400 mesh) using an n-hexane–AcOEt mixture as
eluent.
3-Propyl-2-thioxo-1,3-thiazinan-4-one (3a). Yellow oil,9 yield: 0.32 g (85%). IR (KBr)
(vmax/cm−1): 1705, 1372, 1226, 1179. 1H NMR (250.1 MHz, CDCl3): δH = 0.92 (t, J = 7.5 Hz, 3H,
CH3), 1.59-1.74 (m, 2H, CH2CH3), 2.99-3.15 (m, 4H, 2CH2), 4.27-4.34 (m, 2H, NCH2). 13C
NMR (62.5 MHz, CDCl3): δC = 11.1 (CH3), 20.5 (CH2CH3), 25.6 and 34.1 (2CH2), 48.5 (NCH2),
167.0 (C=O), 200.8 (C=S). MS: m/z: 189 (M+, 100), 156 (18), 133 (17), 118 (21), 100 (65), 89
(17), 72 (23), 60 (20), 55 (24).
3-Isopropyl-2-thioxo-1,3-thiazinan-4-one (3b). Yellow crystal, yield: 0.32 g (85%), mp
= 48-50 oC.9 IR (KBr) (vmax/cm−1): 1705, 1361, 1271, 1187. 1H NMR (250.1 MHz, CDCl3) δH =
13
1.46 (d, J = 6.7 Hz, 6H, 2CH3), 2.93-3.08 (m, 4H, 2CH2), 5.73 (m, 1H, CH). C NMR (62.5
MHz, CDCl3): δC = 19.7 (2CH3), 24.0 and 35.9 (2CH2), 54.4 (CH), 167.1 (C=O), 202.7 (C=S).
MS: m/z: 189 (M+, 55), 156 (22), 133 (15), 100 (100), 60 (15).
3-(2-Hydroxyethyl)-2-thioxo-1,3-thiazinan-4-one (3c). Yellow oil, yield: 0.27 g (72%).
1
IR (KBr) (vmax/cm−1): 3422, 1709, 1328, 1279, 1156. H NMR (300.1 MHz, CDCl3): δH = 2.12
(bs, 1H, OH), 3.08-3.12 and 3.17-3.22 (2m, 4H, 2CH2), 3.92 (t, J = 5.5 Hz, 2H, OCH2), 4.69 (t, J
13
= 5.5 Hz, 2H, NCH2). C NMR (75.5 MHz, CDCl3): δC = 25.2 and 33.5 (2CH2), 48.3 (NCH2),
60.3 (OCH2), 167.7 (C=O), 201.5 (C=S). MS: m/z: 191.0 (M+, 18), 174 (21), 119 (50), 104 (40),
86 (45), 60 (100), 55 (95). Anal.Calcd for C6H9NO2S2: (191.3), C, 37.68; H, 4.74; N, 7.32.
Found: C, 37.50; H, 4.76; N, 7.30.
3-[(2-Hydroxyethoxy)methyl]-2-thioxo-1,3-thiazinan-4-one (3d). Yellow oil, yield:
1
0.33 g (70%). IR (KBr) (vmax/cm−1): 3426, 1711, 1328, 1281, 1174. H NMR (300.1 MHz,
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CDCl3): δH = 2.08-2.20 (bs, 1H, OH), 3.06-3.09 and 3.15-3.19 (2m, 4H, 2CH2), 3.58-3.61 and
3.69-3.72 (2m, 4H, 2OCH2), 3.77 (t, J = 5.0 Hz, 2H, NCH2CH2), 4.71 (t, J = 5.0 Hz, 2H, NCH2).
13C NMR (75.5 MHz, CDCl3): δC = 25.5 and 34.0 (2CH2), 45.3 (NCH2), 61.7, 67.4, and 72.1
(3OCH2), 167.4 (C=O), 201.2 (C=S). MS: m/z: 236 [(M+1)+, 50], 174 (100), 148 (40), 99 (25),
87 (90), 55 (95), Anal.Calcd for C8H13NO3S2: (235.3), C, 40.83; H, 5.57; N, 5.95. Found: C,
40.76; H, 5.59; N, 5.92.
3-Benzyl-2-thioxo-1,3-thiazinan-4-one (3e). Yellow crystal, yield: 0.34 g (72%), mp =
84-85 oC.13 IR (KBr) (vmax/cm−1): 1700, 1383, 1217, 1155. 1H NMR (250.1 MHz, CDCl3): δH =
3.04-3.09 and 3.12-3.19 (2m, 4H, 2CH2), 5.69 (s, 2H, NCH2), 7.27-7.35 (m, 5H, C6H5). 13C
NMR (62.5 MHz, CDCl3): δC = 25.5 and 34.2 (2CH2), 49.1 (NCH2), 127.5 (CH), 128.1 (2CH),
128.4 (2CH), 136.3 (C), 167.1 (C=O), 201.1 (C=S). MS: m/z: 237 (M+, 63), 161 (22), 148 (100),
91 (64), 77 (8). Anal.Calcd for C11H11NOS2 (237.3), C, 55.67; H, 4.67; N, 5.90; Found: C, 55.30;
H, 4.60; N, 5.95.
3-Phenylethyl-2-thioxo-1,3-thiazinan-4-one (3f). Yellow crystal, yield: 0.41 g (81%),
mp = 76-78 oC.13 IR (KBr) (vmax/cm−1): 1710, 1342, 1257, 1132. 1H NMR (300.1 MHz, CDCl3):
δH = 2.97-3.03 (m, 4H, 2CH2), 3.11-3.13 (m, 2H, CH2Ph), 4.59-4.64 (m, 2H, NCH2), 7.24-7.35
13
(m, 5H, C6H5). C NMR (75.5 MHz, CDCl3): δC = 25.5, 33.1, and 34.0 (3CH2), 48.0 (NCH2),
126.6 (CH), 128.5 (2CH), 129.0 (2CH), 138.1 (C), 166.8 (C=O), 200.6 (C=S). MS: m/z: 251
(M+, 12), 140 (23), 86 (60), 91 (38), 55 (100), 77 (15), 69 (49).
(R)-3-(1-Phenylethyl)-2-thioxo-1,3-thiazinan-4-one (3g). Yellow crystal, yield: 0.37g
1
(73%), mp = 101-102 oC. IR (KBr) (vmax/cm−1): 1698, 1377, 1290, 1158. H NMR (250.1 MHz,
CDCl3): δH = 1.80 (d, J = 7.0 Hz, 3H, CH3), 2.84-3.17 (m, 4H, 2CH2), 6.09 (q, J = 7.0 Hz, 1H,
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CH), 7.23-7.38 (m, 5H, C6H5). C NMR (62.5 MHz, CDCl3): δC = 15.7 (CH3), 25.9 and 35.4
(2CH2), 57.9 (CH), 126.4 (2CH), 127.01 (CH), 128.2 (2CH), 140.2 (C), 166.1 (C=O), 202.4
(C=S). MS: m/z: 251 (M+, 56), 167 (19), 162 (100), 149 (48), 105 (50), 77 (18). Anal.Calcd for
C12H13NOS2 (251.4), C, 57.34; H, 5.21; N, 5.57; Found: C, 57.00; H, 5.16; N, 5.52.
3-(2-Chlorobenzyl)-2-thioxo-1,3-thiazinan-4-one (3h). Yellow crystal, yield: 0.39 g
(71%), mp = 135-136 oC. IR (KBr) (vmax/cm−1): 1701, 1359, 1223, 1151. 1H NMR (250.1 MHz,
CDCl3): δH = 3.05-3.08 and 3.15-3.18 (2m, 4H, 2CH2), 5.63 (s, 2H, NCH2), 6.98 (t, J = 8.2 Hz,
13
2H, Ar), 7.34-7.39 (m, 2H, Ar). C NMR (62.5 MHz, CDCl3): δC = 25.6 and 34.2 (2CH2), 47.9
(NCH2), 126.7, 126.9, 128.3, 128.5, and 129.7 (5CH), 133.1 (C), 167.0 (C=O), 200.1 (C=S). MS:
m/z: 272 (M+, 2), 236 (100), 220 (31), 182 (59), 140 (12), 125 (43), 89 (31), 77 (12), 55 (37).
Anal.Calcd for C11H10ClNOS2: (271.8), C, 48.61; H, 3.71; N, 5.15; Found: C, 49.20; H, 3.70; N,
5.12.
3-(4-Fluorobenzyl)-2-thioxo-1,3-thiazinan-4-one (3i). Yellow crystal, yield: 0.45 g
(89%), mp = 104-105 oC. IR (KBr) (vmax/cm−1): 1708, 1332, 1222, 1156. 1H NMR (300.1 MHz,
CDCl3): δH = 3.03-3.08 and 3.14-3.19 (2m, 4H, 2CH2), 5.63 (s, 2H, NCH2), 6.98 (t, J = 8.7 Hz,
13
2H, Ar), 7.34-7.39 (m, 2H, Ar). C NMR (75.5 MHz, CDCl3): δC = 25.5 and 34.1 (2CH2), 48.4
2
(NCH2), 115.2 (d, JCF = 22.0 Hz, 2CH), 130.3 (d, JCF= 8.0 Hz, 2CH), 132.1 (d, JCF = 3.3 Hz,
3
4
1
C), 162.0 (d, JCF = 246.2 Hz, C), 167.1 (C=O), 200.1 (C=S). MS: m/z: 255 (M+, 32), 211 (70),
166 (54), 122 (52), 109 (100), 83 (32). Anal.Calcd for C11H10FNOS2: (255.0), C, 51.74; H, 3.95;
N, 5.49; Found: C, 52.00; H, 3.92; N, 5.51.
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S
S
C
S
O
R
O
Solvent-free
r.t., 15 min
N
S
R NH2
+
+
Cl
1
2
3
R
% Yield of 3
1,3
a
Pr
85
85
72
70
72
81
73
71
b
c
i-Pr
2-Hydroxyethyl
d
e
(2-Hydroxyethoxy)methyl
Benzyl
f
Phenylethyl
g
h
(R)-1-Phenylethyl
2-Chlorobenzyl
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i
4-Fluorobenzyl
Scheme 1
89
S
-
R
+
2
H
N
S
N
H
3
+
RNH3
CS2
S
R NH2
R
Cl
-
+
-
RNH2
S
-
RNH3Cl
O
1
4
5
Scheme 2: Proposed mechanism for synthesis of 2-thioxo-1,3-thiazine-4-one derivatives
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