A one-pot synthesis of N-alkylthiazoline-2-thiones from CS2, primary amines, and 2-chloro-1,3-dicarbonyl compounds in water

Article abstract of DOI:10.1007/s00706-009-0227-2

A simple synthesis of N-alkylthiazoline-2-thiones by reaction of primary amines, carbon disulfide, and 2-chloro-1,3-dicarbonyl compounds in water is described. Proceeding without catalyst under one-pot conditions in high yields and with broad scope, this method high synthetic utility.

Full text of DOI:10.1007/s00706-009-0227-2

Monatsh Chem (2010) 141:49–52
DOI 10.1007/s00706-009-0227-2
ORIGINAL PAPER
A one-pot synthesis of N-alkylthiazoline-2-thiones from CS2,
primary amines, and 2-chloro-1,3-dicarbonyl compounds in water
•
Issa Yavari Mehdi Sirouspour Sanaz Souri
•
Received: 1 August 2009 / Accepted: 21 November 2009 / Published online: 16 December 2009
Ó Springer-Verlag 2009
Abstract A simple synthesis of N-alkylthiazoline-2-
thiones by reaction of primary amines, carbon disulfide,
and 2-chloro-1,3-dicarbonyl compounds in water is
described. Proceeding without catalyst under one-pot
conditions in high yields and with broad scope, this method
high synthetic utility.
phosphate in DMF at room temperature [10]. Recently we
described a synthesis of ethyl 3-alkyl-4-oxo-2-thioxo-1,3-
thiazolane-5-carboxylates by reaction of primary amines
with CS2 in the presence of diethyl 2-chloromalonate [11].
In this paper, a simple synthesis of N-alkylthiazoline-2-
thiones by reaction of primary amines, carbon disulfide,
and 2-chloro-1,3-dicarbonyl compounds in water is
described; the reaction is a development of the pathway
reported by Lamon and Humphlett as a three-component
procedure in water (Scheme 1). This new catalyst-free,
one-pot synthetic method seems facile; the work-up pro-
cedure is easy and gives pure target compounds containing
several potential centers for further modification.
Keywords N-Alkylthiazoline-2-thione Á Primary amine Á
Carbon disulfide Á 2-Chloro-1,3-dicarbonyls
Introduction
Thiazoline-2-thiones are an important class of heterocyclic
compounds. They are used as powerful ligands, which react
with copper(II) chloride and bromide [1] and silver(I)
bromide [2]. N-Alkylthiazoline-2-thiones are precursors in
the synthesis of some electron-rich olefins, which are used
as readily accessible cation radical species and act as a
molecular conductors [3, 4]. In addition, N-alkylthiazoline-
2-thiones are used as a diffusion transfer color photo-
graphic materials [5].
Results and discussion
The reaction of primary amines, carbon disulfide, and
2-chloro-1,3-dicarbonyl compounds in water produced
N-alkylthiazoline-2-thiones 3 in high yields. The structures
of compounds 3a–3i were apparent from elemental anal-
ysis, mass, IR, and NMR spectra. Mass spectra, in
particular, showed the molecular ion peaks at the appro-
priate m/z values. The 1H and 13C NMR spectroscopic
data, and IR spectra, are in agreement with the proposed
Synthesis of N-alkylthiazoline-2-thiones by treatment of
alkylammonium dithiocarbamates with a-haloketones fol-
lowed by cyclization and dehydration in the presence of an
acid has been reported [3, 6–9]. Ethyl 3-alkyl-4-hydroxy-2-
thioxothiazolidine-4-carboxylates have been prepared in
excellent yields by reaction of the corresponding primary
amines with carbon disulfide and ethyl 3-bromo-2-oxo-
propanoate in the presence of anhydrous potassium
1
structures. The H NMR spectrum of 3a in CDCl3 showed
three sharp singlets for the methyl protons. The 13C NMR
spectrum of 3a exhibited seven signals in agreement with
the proposed structure. The 1H NMR and 13C NMR
spectra of 3b–3i are similar to those for 3a except for the
substituents, which showed characteristic resonances in
appropriate regions of the spectrum. After reaction of
4-chlorobenzylamine, CS2, and ethyl 3-chloroacetoacetate
at room temperature intermediate 6i was isolated and
characterized.
I. Yavari (&) Á M. Sirouspour Á S. Souri
Chemistry Department, Tarbiat Modares University,
P.O. Box 14115-175, Tehran, Iran
e-mail: yavarisa@modares.ac.ir
123

50
I. Yavari et al.
Scheme 1
S
R
O
O
N
S
water
reflux
R-NH2
CS2
+
+
R'
R'
Cl
R'
O
2
3
Yield (%)
R'
1
R
R
a
b
c
Me
n-Bu
4-Cl-Bn
Me
Me
Me
Me
Me
Me
Me
Me
OEt
80
85
78
82
75
68
85
65
85
a
b
c
d
e
f
g
h
a
b
Me
n-Bu
4-Cl-Bn
4-Me-Bn
4-MeO-Bn
2-Cl-Bn
1-Naphthyl-CH2
Ph
Me
OEt
d
4-Me-Bn
4-MeO-Bn
2-Cl-Bn
e
f
g
1-Naphthyl-CH2
h Ph
i
4-Cl-Bn
S
Elemental analyses for C, H, N were performed using a
Heraeus CHN-O-Rapid analyzer, and the results agreed
favorably with calculated values.
2
+
R
2 R-NH
2+ CS2
RNH3
S
N
_
H
RNH3 Cl
4
O
O
S
General procedure for the synthesis
of N-alkylthiazoline-2-thiones 3
R
R'
_
cyclization
N
S
H2O
3
S
NHR
HO
R'
To amine 1 (4 mmol) and 0.92 g CS2 (12 mmol) in 7 cm3
water was slowly added 2-chloro-1,3-dicarbonyl compound
2 (2 mmol). The reaction mixture was stirred for 2 h at rt
and heated under reflux for 4–5 h. Addition of 4 cm3 sat-
urated NaHCO3 solution caused an oil to separate, which in
some cases solidified on standing overnight. The residue
was recrystallized from n-hexane–toluene mixtures.
S
O
5
6
Scheme 2
Mechanistically, the reaction starts with formation of an
alkylammonium dithiocarbamate salt 4, followed by addi-
tion to 2-chloro-1,3-dicarbonyl compounds to generate the
acyclic dithiocarbamate derivatives 5. Subsequent cycli-
zation yields 4-hydroxythiazoline-2-thiones 6. Elimination
of water from 6 in the presence of alkylammonium chloride
leads to N-alkylthiazoline-2-thiones 3 (Scheme 2).
In conclusion, we have described a convenient route to
N-alkylthiazoline-2-thiones 3 by reaction of primary
amines, CS2, and 2-chloro-1,3-dicarbonyl compounds. This
catalyst-free and green procedure may be regarded as an
alternative method for preparation of N-alkylthiazoline-2-
thiones.
1-(2,3-Dihydro-3,4-dimethyl-2-thioxothiazol-5-yl)-1-
ethanone (3a, C7H9NOS2)
1
Pale brown oil; yield 0.30 g (80%); H NMR (500 MHz,
CDCl3): d = 2.40 (s, CH3), 2.67 (s, CH3), 4.19 (s, CH3)
ppm; 13C NMR (125.7 MHz, CDCl3): d = 14.4 (CH3),
29.9 (CH3), 41.0 (CH3N), 121.2 (C), 146.9 (C), 187.3 (C),
ꢀ
188.2 (C) ppm; IR (KBr): m = 1,669 (C=O), 1,648, 1,550,
1,460, 1,430, 1,361, 1,303, 1,279, 1,210, 1,140, 1,123,
990 cm-1; EI-MS: m/z (%) 187 (M?, 10), 158 (45), 154
(100), 71 (16), 29 (40).
1-(3-Butyl-2,3-dihydro-4-methyl-2-thioxothiazol-5-yl)-1-
ethanone (3b, C10H15NOS2)
Experimental
1
Pale yellow oil; yield 0.39 g (85%); H NMR (500 MHz,
3
CDCl3): d = 0.90 (t, J = 7.5 Hz, CH3), 1.35 (m, CH2),
All purchased solvents and chemicals were of analytical
grade and used without further purification. Melting points
and IR spectra of all compounds were measured on an
Electrothermal 9100 apparatus and a Shimadzu IR-460
1.61 (m, CH2), 2.27 (s, CH3), 2.60 (s, CH3), 4.12 (t,
3J = 7.5 Hz, CH2N) ppm; 13C NMR (125.7 MHz, CDCl3):
d = 13.3 (CH3), 14.4 (CH3), 19.7 (CH2), 29.1 (CH2), 29.9
(CH3), 47.0 (CH2N), 120.0 (C), 146.5 (C), 187.1 (C), 187.7
spectrometer, respectively. The H and 13C NMR spectra
1
ꢀ
(C) ppm; IR (KBr): m = 1,663 (C=O), 1,640, 1,549, 1,448,
were obtained on a Bruker DRX-500 Avance instrument
using CDCl3 as solvent and TMS as internal standard at
500 and 125.7 MHz, respectively. The mass spectra were
recorded on an HP (Agilent Technology) GCMSQP5050A.
1,417, 1,355, 1,300, 1,274, 1,197, 1,157, 1,121, 1,030,
974 cm-1; EI-MS: m/z (%) = 229 (M?, 15), 196 (60), 158
(55), 71 (16), 43 (100).
123

Synthesis of N-alkylthiazoline-2-thiones
51
1-[3-[(4-Chlorophenyl)methyl]-2,3-dihydro-4-methyl-2-
thioxothiazol-5-yl]-1-ethanone (3c, C13H12ClNOS2)
Pale yellow crystals; yield 0.46 g (78%); m.p.: 119–
1-[2,3-Dihydro-4-methyl-3-(1-naphthylmethyl)-2-
thioxothiazol-5-yl]-1-ethanone (3g, C17H15NOS2)
Pale yellow crystals; yield 0.53 g (85%); m.p.: 202–
1
1
122 °C; H NMR (500 MHz, CDCl3): d = 2.36 (s, CH3),
204 °C; H NMR (500 MHz, CDCl3): d = 2.48 (s, CH3),
2.60 (s, CH3), 6.14 (s, CH2N), 6.81 (d, J = 7.0 Hz, CH),
2.52 (s, CH3), 5.51 (s, CH2N), 7.13 (d, 3J = 8.3 Hz, 2 CH),
3
3
3
7.43 (t, J = 8.0 Hz, CH), 7.61 (t, J = 7.0 Hz, CH), 7.67
3
7.29 (d, J = 8.3 Hz, 2 CH) ppm; 13C NMR (125.7 MHz,
3
(t, J = 7.0 Hz, CH), 7.90 (d, J = 8.0 Hz, CH), 8.00 (d,
3
CDCl3): d = 15.0 (CH3), 30.3 (CH3), 49.7 (CH2N), 120.5
(C), 128.1 (2 CH), 129.3 (2 CH), 132.6 (C), 134.1 (C),
3
3J = 8.0 Hz, CH), 8.19 (d, J = 8.0 Hz, CH) ppm; 13C
ꢀ
146.9 (C), 188.0 (C), 188.7 (C) ppm; IR (KBr): m = 1,665
(C=O), 1,639, 1,552, 1,481, 1,418, 1,354, 1,297, 1,295,
NMR (125.7 MHz, CDCl3): d = 15.1 (CH3), 30.2 (CH3),
48.9 (CH2N), 122.2 (C), 122.6 (CH), 123.4 (CH), 126.3
(CH), 127.1 (CH), 127.5 (CH), 128.9 (CH), 129.8 (CH),
130.7 (C), 131.3 (C), 134.8 (C), 148.1 (C), 188.2 (C), 189.5
1,200, 1,157, 1,087, 982, 792 cm-1
; EI-MS: m/z
(%) = 298 (M?, 15), 265 (42), 158 (20), 140 (10), 126
ꢀ
(100).
(C) ppm; IR (KBr): m = 1,638 (C=O), 1,561, 1,499, 1,418,
1,378, 1,352, 1,298, 1,285, 1,199, 1,157, 1,045, 1,020, 989,
911, 783 cm-1; EI-MS: m/z (%) = 313 (M?, 30), 280 (25),
158 (35), 155 (25), 141 (100).
1-[2,3-Dihydro-4-methyl-3-[(4-methylphenyl)methyl]-2-
thioxothiazol-5-yl]-1-ethanone (3d, C14H15NOS2)
Pale yellow crystals; yield 0.45 g (82%); m.p.: 129–
1
130 °C; H NMR (500 MHz, CDCl3): d = 2.30 (s, CH3),
1-(2,3-Dihydro-4-methyl-3-phenyl-2-thioxothiazol-5-yl)-1-
ethanone (3h, C12H11NOS2)
2.42 (s, CH3), 2.59 (s, CH3), 5.63 (s, CH2N), 7.17–7.22 (m,
4 CH) ppm; 13C NMR (125.7 MHz, CDCl3): d = 15.3
(CH3), 21.0 (CH3), 30.4 (CH3), 50.6 (CH2N), 122.0 (C),
127.5 (2 CH), 130.3 (2 CH), 132.9 (C), 138.3 (C), 148.0
Yellow crystals; yield 0.32 g (65%); m.p.: 175–177 °C; 1H
NMR (500 MHz, CDCl3): d = 2.32 (s, CH3), 2.45 (s,
CH3), 7.34–7.44 (m, 2 CH), 7.54–7.66 (m, 3 CH) ppm; 13
C
ꢀ
(C), 188.6 (C), 189.9 (C) ppm; IR (KBr): m = 1,651 (C=O),
NMR (125.7 MHz, CDCl3): d = 16.5 (CH3), 30.9 (CH3),
123.0 (C), 129.5 (2 CH), 130.6 (CH), 130.8 (2 CH), 138.8
(C–N), 148.0 (C), 188.6 (C), 190.6 (C) ppm; IR (KBr):
1,640, 1,542, 1,506, 1,419, 1,368, 1,362, 1,295, 1,290,
1,178, 1,168, 802, 744 cm-1; EI-MS: m/z (%) = 277 (M?,
10), 244 (35), 158 (10), 140 (25), 105 (100).
ꢀ
m = 16,705 (C=O), 1,650, 1,555, 1,510, 1,444, 1,348,
1,294, 1,249, 1,160, 810 cm-1; EI-MS: m/z (%) = 249
1-[2,3-Dihydro-3-[(4-methoxyphenyl)methyl]-4-methyl-2-
thioxothiazol-5-yl]-1-ethanone (3e, C14H15NO2S2)
(M?, 22), 216 (28), 158 (18), 64 (22), 42 (100).
Yellow crystals; yield 0.44 g (75%); m.p.: 135–137 °C; 1H
NMR (500 MHz, CDCl3): d = 2.33 (s, CH3), 2.52 (s,
CH3), 3.75 (s, CH3O), 5.47 (s, CH2N), 6.82 (d,
Ethyl 3-[(4-chlorophenyl)methyl]-2,3-dihydro-4-methyl-2-
thioxothiazol-5-carboxylate (3i, C14H14ClNO2S2)
Pale yellow crystals; yield 0.56 g (85%); m.p.: 64–67 °C;
3
3
3J = 8.6 Hz, 2 CH), 7.14 (d, J = 8.6 Hz, 2 CH) ppm;
1H NMR (500 MHz, CDCl3): d = 1.32 (t, J = 7.1 Hz,
13C NMR (125.7 MHz, CDCl3): d = 14.8 (CH3), 30.1
(CH3), 49.7 (CH2N), 55.1 (CH3O), 114.2 (2 CH), 120.2
(C), 125.9 (C), 127.9 (2 CH), 147.1 (C), 159.2 (C–O),
CH3), 2.53 (s, CH3), 4.29 (q, 3J = 7.1 Hz, CH2O), 5.50 (s,
CH2N), 7.14 (d, 3J = 7.3 Hz, 2 CH), 7.28 (d, 3J = 7.3 Hz,
2 CH) ppm; 13C NMR (125.7 MHz, CDCl3): d = 14.1
(CH3), 14.3 (CH3), 49.6 (CH2N), 61.6 (CH2O), 128.0 (CH),
128.6 (C), 129.1 (CH), 132.7 (C), 133.9 (C), 147.9 (C),
ꢀ
187.8 (C), 188.4 (C) ppm; IR (KBr): m = 1,664 (C=O),
1,638, 1,551, 1,503, 1,432, 1,350, 1,295, 1,244, 1,177,
1,155, 1,025, 806 cm-1; EI-MS: m/z (%) = 293 (M?, 7),
260 (30), 158 (10), 156 (20), 121 (100).
ꢀ
159.8 (C=O), 189.7 (C=S) ppm; IR (KBr): m = 1,690
(C=O), 1,641, 1,562, 1,474, 1,400, 1,350, 1,293, 1,230,
1,210, 1,137, 1,080, 972, 785 cm-1
; EI-MS: m/z
1-[3-[(2-Chlorophenyl)methyl]-2,3-dihydro-4-methyl-2-
thioxothiazol-5-yl]-1-ethanone (3f, C13H12ClNOS2)
Pale yellow crystals; yield 0.41 g (68%); m.p.: 114–
(%) = 328 (M?, 10), 295 (31), 283 (40), 188 (15), 140
(12), 126 (100).
1
116 °C; H NMR (500 MHz, CDCl3): d = 2.40 (s, CH3),
Ethyl 3-[(4-chlorophenyl)methyl]-4-hydroxy-4-methyl-2-
thioxothiazolidine-5-carboxylate (6i, C14H16ClNO3S2)
Colorless crystals; yield 0.66 g (95%); m.p.: 224–230 °C; 1H
2.51 (s, CH3), 5.65 (s, CH2N), 7.17–7.40 (m, 3 CH), 7.45
(d, 3J = 8.5 Hz, CH) ppm; 13C NMR (125.7 MHz,
CDCl3): d = 14.6 (CH3), 30.2 (CH3), 47.7 (CH2N), 120.3
(C), 126.4 (CH), 126.7 (CH), 129.2 (CH), 129.4 (CH),
131.3 (C), 132.3 (C), 146.9 (C), 186.0 (C), 188.7 (C) ppm;
3
NMR (500 MHz, CDCl3): d = 1.29 (t, J = 7.1 Hz, CH3),
3
1.59 (s, CH3), 4.06 (s, CH), 4.25 (q, J = 7.1 Hz, CH2O),
4.84 (d, 2J = 15.2 Hz, CH), 5.10 (d, 2J = 15.2 Hz, CH), 5.19
(s, OH), 7.28 (d, 3J = 8.3 Hz, 2 CH), 7.34 (d, 3J = 8.3 Hz, 2
CH) ppm; 13C NMR (125.7 MHz, CDCl3): d = 13.9 (CH3),
24.4 (CH3), 47.5 (CH2N), 51.8 (CH), 63.0 (CH2), 97.9 (C),
128.7 (2 CH), 129.0 (2 CH), 133.3 (C), 135.0 (C), 169.9
ꢀ
IR (KBr): m = 1,660 (C=O), 1,640, 1,550, 1,481, 1,424,
1,350, 1,291, 1,285, 1,200, 1,143, 1,079, 980, 790 cm-1
;
EI-MS: m/z (%) = 298 (M?, 20), 265 (35), 158 (20), 140
(15), 126 (100).
123

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I. Yavari et al.
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(C=O), 191.6 (C=S) ppm; IR (KBr): ꢀm = 3,410 (OH), 1,705
(C=O), 1,561, 1,499, 1,418, 1,378, 1,352, 1,298, 1,285, 1,199,
1,157, 1,045, 1,020, 989, 911, 783 cm-1; EI-MS: m/z
(%) = 346 (M?, 5), 328 (20), 295 (15), 283 (31), 188 (8),
140 (20), 126 (100).
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123