Synthesis of Thioalkyne-Substituted Thiazolidine-2-thiones Using Tris(triAmethylsilyl)methyllithium and Carbon Disulfide

Article abstract of DOI:10.1055/s-0034-1379253

An efficient, environmentally benign, and simple one-pot approach to the synthesis of 5-(iodomethyl)thiazolidine-2-thiones via multicomponent reaction of allylamines, carbon disulfide, and iodine under solvent-free conditions is presented. The obtained 5-(iodomethyl)thiazolidine-2-thiones were converted into silyl-protected-terminal [(ethynylthio)methyl]-substituted thiazolidine-2-thiones by treatment with lithium 2,2,2-tris(trimethylsilyl)ethanedithioate, produced by the reaction of tris(trimethylsilyl)methyllithium with carbon disulfide.

Full text of DOI:10.1055/s-0034-1379253

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 256–262
paper
256
K. D. Safa, M. Alyari
Paper
Synthesis
Synthesis of Thioalkyne-Substituted Thiazolidine-2-thiones Using
Tris(trimethylsilyl)methyllithium and Carbon Disulfide
Silyl-Protected Terminal Thioalkynes
Kazem Dindar Safa*
Maryam Alyari
S
S
R
R
I2, K2CO3
CS2, (Me3Si)3CLi
THF, 0 °C
N
N
S
S
+
CS2
RHN
Organosilicon Research Laboratory, Faculty of Chemistry,
University of Tabriz, 5166616471, Tabriz, Iran
dsafa@tabrizu.ac.ir
solvent-free
S
I
SiMe3
Received: 22.07.2014
Accepted after revision: 18.09.2014
Published online: 06.11.2014
lidine-2-thiones have received considerable attention be-
cause of their wide range of applications and the diverse
biological activity of many representatives of this class of
compounds.8,9
DOI: 10.1055/s-0034-1379253; Art ID: ss-2014-z0456-op
Abstract An efficient, environmentally benign, and simple one-pot
approach to the synthesis of 5-(iodomethyl)thiazolidine-2-thiones via
multicomponent reaction of allylamines, carbon disulfide, and iodine
under solvent-free conditions is presented. The obtained 5-(iodometh-
yl)thiazolidine-2-thiones were converted into silyl-protected terminal
[(ethynylthio)methyl]-substituted thiazolidine-2-thiones by treatment
with lithium 2,2,2-tris(trimethylsilyl)ethanedithioate, produced by the
reaction of tris(trimethylsilyl)methyllithium with carbon disulfide.
In recent years a central purpose in synthetic organic
chemistry has been to develop greener and economically
competitive processes for the efficient synthesis of biologi-
cally active compounds. It reduces the use of organic sol-
vents and minimizes the formation of other waste. Recent-
ly, Ziyaei-Halimehjani and co-workers described a one-pot,
three-component reaction for the synthesis of thiazolidine-
2-thione involving the reaction of allylamines with carbon
disulfide in tetrahydrofuran to afford dithiocarbamate salts,
then iodocyclization of these new compounds produced 5-
(iodomethyl)thiazolidine-2-thiones.5
Key words thioalkyne, thiazolidine-2-thione, organosilicon, organo-
sulfur, tris(trimethylsilyl)methyllithium, carbon disulfide
Thioalkynes are a desirable platform for drug diversifi-
cation considering the variety of existing acetylene chemis-
try, in particular the extensively used copper-catalyzed
azide-alkyne cycloaddition, and the powerful position of
organosulfur compounds among top-selling pharmaceuti-
cal drugs. Existing methods to form S–Csp bonds are rare
and require harsh conditions. Currently, the most common
techniques require functionalization of the thiol.1 In this
paper, we set out to investigate the feasibility of a facile and
efficient method to gain access to a thioalkyne substituent
on a thiazolidine-2-thione, because of the exceptional reac-
tivity of sulfur and its importance in biology, medicine, and
material science. Of particular interest to us are silylacety-
lenes as a direct gateway to the most versatile terminal
alkynes in various biologically important compounds.
Nitrogen-containing five- or six-membered heterocyclic
compounds are of great interest to organic chemists be-
cause of their presence in various natural compounds; they
have interesting bioactivity.2 Thiazolidine-2-thione is a
five-membered heterocyclic compound, containing sulfur
and nitrogen atoms attached to the carbon of a C=S group,
that has been extensively studied in recent years.3–7 Thiazo-
This reported method suffers from several disadvantag-
es such as the use of harmful organic solvents, prolonged
reaction times, and unsatisfactory yields. Therefore search-
ing for more facile and practical synthetic routes to thiazoli-
dine-2-thiones remains desirable. To improve the synthesis
of thiazolidine-2-thiones, herein we report a novel, effi-
cient, and green synthesis of these compounds under sol-
vent-free conditions by the three-component reaction of an
allylamine, carbon disulfide, and iodine.
The reaction of N-benzylallylamine (1c) (3 mmol), car-
bon disulfide (5 mmol), and iodine (3.3 mmol) in tetrahy-
drofuran at room temperature for 24 hours without a cata-
lyst, afforded the desired thiazolidine-2-thione 2c in 60%
yield.5 In order to improve the reaction efficiency, we varied
the molar ratios of the reactions and used potassium car-
bonate as a catalyst (Scheme 1,Table 1). Potassium dithio-
carbamates are obtained by treating allylamines with car-
bon disulfide in the presence of potassium carbonate. This
method has the advantage that only one equivalent of
amine is required. When a 1:3:4 ratio of 1c/carbon disul-
fide/iodine was used in the presence of potassium carbon-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 256–262

257
K. D. Safa, M. Alyari
Paper
Synthesis
ate, the product was isolated in the highest yields among
those in Table 1 (entries 5, 6 and 11). Lowering the amount
of iodine increased the reaction time and decreased the
yield (entries 1–3). To our delight, when the reaction was
carried out in water for 40 minutes 2c was obtained in high
yield (entry 5). The use of a co-solvent or an organic solvent
was not beneficial to the process (entries 7–10). We ob-
served that under solvent-free conditions at room tempera-
ture the one-pot reaction proceeded to completion, afford-
ing the thiazolidine-2-thione 2c in good yield; the reaction
conditions were then finally established as shown in entry
11.
Table 2 One-Pot Synthesis of Thiazolidine-2-thiones
S
R
I2, K2CO3
N
S
CS2
+
RHN
solvent-free, r.t.
1
I
2a–l
Entry
R
Product
Time/min
Yielda (%)
1
H
2a
2b
2c
2d
2e
2f
30
40
30
25
25
45
30
40
60
60
50
45
93
85
90
90
92
80
91
83
80
80
83
85
2
CH2Cy
Bn
3
S
4
4-MeC6H4CH2
4-i-PrC6H4CH2
(E)-CH2CH=CHPh
4-ClC6H4CH2
5
N
S
I2
N
H
CS2
+
6
I
7
2g
2h
2i
1c
2c
8
3-ClC6H4CH2
Scheme 1
9
1-naphthylmethyl
2-furylmethyl
Table 1 Optimization of the Synthesis of 3-Benzyl-5-(iodomethyl)thi-
azolidine-2-thione (2c)
10
11
12
2j
5-methyl-2-furylmethyl 2k
2-thienylmethyl 2l
Entry Ra-
tio1c/CS2/
Catalyst (equiv) Solvent
Time
(min)
Yielda (%)
a Isolated yield.
I2 (equiv)
1
2
3
4
5
6
7
8
9
10
1:3:1
1:3:1.5
1:3:1.5
1:3:4
1:3:4
1:3:4
1:3:4
1:3:4
1:3:4
1:3:4
none
H2O
60
60
50
50
40
35
72
75
81
83
85
87
70
68
78
75
disulfide at –46 °C. To extend our investigations to organo-
silicon compounds, we decided to study the reaction of
tris(trimethylsilyl)methyllithium with carbon disulfide in
the presence of various 5-(iodomethyl)thiazolidine-2-thi-
ones at temperatures ranging from 0 to 25 °C.
The precursor tris(trimethylsilyl)methane was prepared
by the reaction of chloroform, lithium, and chlorotrimethyl-
silane in tetrahydrofuran. The organolithium reagent
tris(trimethylsilyl)methyllithium was obtained by treat-
ment of tris(trimethylsilyl)methane with methyllithium at
reflux in tetrahydrofuran (Scheme 2).15
none
H2O
K2CO3 (0.5)
none
H2O
H2O
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
H2O
H2O (50 °C)
THF
120
120
50
CH2Cl2
EtOH
EtOH–H2O
(1:1)
50
THF
11
1:3:4
K2CO3 (0.5)
neat
30
90
Me3SiCl + CHCl3 + 6 Li
(Me3Si)3CH + 6 LiCl
2 h
a Isolated yield.
MeLi
(Me3Si)3CLi
Encouraged by these results, the synthesis of thiazoli-
dine-2-thiones 2a–l was carried out using four equivalents
of iodine under solvent-free conditions (Table 2). It should
be noted that in all of these experiments the alternative 6-
endo-trig cyclization was not detected.
We have recently used bulky tris(trimethylsilyl)methyl-
lithium as a reagent in various reactions such as the prepa-
ration of vinylsilanes, epoxysilanes, halovinylsilanes, silyl
ethers, etc.10–13 In addition we have investigated its behav-
ior with carbon disulfide at low temperatures.14 In the pre-
vious publications we reported a new type of chemistry of
carbon disulfide proceeding via nucleophilic attack of
tris(trimethylsilyl)methyllithium at the carbon of carbon
Scheme 2 Preparation of tris(trimethylsilyl)methyllithium
We began our study with 3-benzyl-5-(iodomethyl)thi-
azolidine-2-thione (2c) as a model substrate. In our experi-
ments, carbon disulfide was added in one portion to a solu-
tion consisting of the tris(trimethylsilyl)methyllithium and
tetrahydrofuran and this was stirred for 15 minutes. The
color of the solution changed to orange-red immediately,
which indicates the formation of new anion. Then, a solu-
tion of 2c in tetrahydrofuran was added slowly and drop-
wise to the stirred solution. The product 3c, with a silyl-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 256–262

258
K. D. Safa, M. Alyari
Paper
Synthesis
protected terminal alkyne, was isolated in 85% yield at 0 °C
as the main product and only a trace amount of product 4
was obtained at this temperature (Scheme 3). The yield of 4
increased with increasing temperature and at room tem-
perature both products were obtained approximately in
equal yields.
Table 3 Synthesis of N-Substituted 5-({[(Trimethylsilyl)ethyn-
yl]thio}methyl)thiazolidine-2-thiones
S
S
R
R
(Me3Si)3CLi, CS2
0 °C, THF
N
N
S
S
S
(Me3Si)3CLi
S
I
2
CS2
N
S
0 °C
SiMe3
3
S
S
Entry
R
Product
Yielda (%)
N
S
1
H
3a
3b
3c
3d
3e
3f
75
83
85
88
90
83
87
80
78
82
85
85
SiMe3
S
3c
2
CH2Cy
Bn
I
2c
3
(Me3Si)3CLi
CS2
N
4
4-MeC6H4CH2
S
3c
+
r.t.
5
4-i-PrC6H4CH2
6
(E)-CH2CH=CHPh
4-ClC6H4CH2
HS
4
7
3g
3h
3i
Scheme 3 Reaction of tris(trimethylsilyl)methyllithium and carbon di-
sulfide with 2c
8
3-ClC6H4CH2
9
1-naphthylmethyl
2-furylmethyl
10
11
12
3j
The reaction of various 5-(iodomethyl)thiazolidine-2-
thiones 2 was studied and the results are summarized in
Table 3; all experiments were carried out at 0 °C.
5-methyl-2-furylmethyl
2-thienylmethyl
3k
3l
a Isolated yield.
On the basis of the experimental results and the litera-
ture,6,16–18 a possible mechanism for the formation of thio-
alkyne derivatives is presented in Scheme 4. According to
the literature, the reaction of carbon disulfide with organo-
lithium compounds leads to the formation of two different
types of intermediate, 1,1-dithioenolates RHC=C(SLi)2 and
dithiocarboxylates RC(S)SLi. In the present work, addition
of carbon disulfide to tris(trimethylsilyl)methyllithium at
0 °C produced lithium 2,2,2-tris(trimethylsilyl)ethanedi-
thioate (Me3Si)3C(S)SLi as an intermediate, which subse-
quently reacted with 5-(iodomethyl)thiazolidine-2-thiones
2 to give the final products 3.
In conclusion, we have reported a highly efficient and
green protocol for the one-pot synthesis of thiazolidine-2-
thione derivatives starting from amines, carbon disulfide,
and iodine. Then we have described a novel and efficient
preparation of silyl-protected terminal ethynylthio-substi-
tuted thiazolidine-2-thiones from the reaction of the lithi-
um 2,2,2-tris(trimethylsilyl)ethanedithioate intermediate
with various thiazolidine-2-thiones.
S
R
N
S
S
Me3Si
2
Me3Si
Me3Si
Me3Si CLi
CS2
+
SLi
Me3Si
S
SiMe3
S
S
Me3Si
R
Me3Si SiMe3
N
a
S
Li+–
S
S
3
R
N
S
SiMe3
S
a
R
S
b
N
S
S–
Li+
b
Me3Si
SiMe3
HS
4
Scheme 4 The mechanism of the reaction of tris(trimethylsilyl)methyl-
lithium, carbon disulfide, and 5-(iodomethyl)thiazolidine-2-thiones
Reactions were carried out under dry argon. Solvents and carbon di-
sulfide were dried by standard methods. Substrates for the prepara-
tion of tris(trimethylsilyl)methyllithium, namely chlorotrimethylsi-
lane (Merck), lithium (Merck), chloroform (Merck) and substrates for
the preparation of thiazolidine-2-thione, namely allylamines, carbon
disulfide (Merck), n-hexane (Merk) and ethyl acetate (Merck) for TLC,
were used as received.
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K. D. Safa, M. Alyari
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1H and 13C NMR were recorded with a Bruker FT-400MHz spectrome-
ter at room temperature and CDCl3 as a solvent. The mass spectra
were obtained with a GC-mass Agilent quadrupole mode 5973N in-
strument, operating at 70 eV. Fourier transform infrared spectroscopy
(FTIR) was performed using a Bruker-Tensor 270 spectrophotometer.
Elemental analyses were carried out on a Vario EL III instrument.
13C NMR (100 MHz, CDCl3): δ = 28.68, 41.22, 45.96, 52.43, 121.67,
125.52, 125.61, 127.32, 127.44, 133.41, 133.61, 194.10 (C=S).
Anal. Calcd for C13H14INS2: C, 41.60; H, 3.76; N, 3.73. Found: C, 41.81;
H, 3.99; N, 3.52.
3-(3-Chlorobenzyl)-5-(iodomethyl)thiazolidine-2-thione (2h)
Yellow sticky solid; yield: 0.32 g (83%); Rf = 0.45 (n-hexane–EtOAc,
3:1).
3-Substituted 5-(Iodomethyl)thiazolidine-2-thiones 2; General
Procedure
IR (KBr): 1486, 1416, 1257, 1168, 821, 557 cm–1
.
N-Substituted allylamine 1 (1 mmol), K2CO3 (0.5 mmol), and CS2 (3
mmol) were added to a test tube equipped with a magnetic stir bar.
The mixture was stirred for 5 min, I2 (4 mmol) was added and stirring
was maintained until the reaction was complete (TLC). Then the mix-
ture was treated with 2 M aq NaHSO3 solution (5 mL) and extracted
with CH2Cl2 (2 × 10 mL). The organic layer was dried (Na2SO4) and
evaporated under reduced pressure to give the crude product. Purifi-
cation was achieved by recrystallization (EtOH). Compounds 2a,c,d,g,i
have been described previously.5
1H NMR (400 MHz, CDCl3): δ = 3.22 (t, J = 10.61 Hz, 1 H, CHI), 3.35 (dd,
J = 4.28, 10.10 Hz, 1 H, CHI), 3.77–3.83 (m, 1 H, H5), 3.87 (dd, J = 2.10,
12.21 Hz, 1 H, H4), 4.00 (dd, J = 12.21, 14.42 Hz, 1 H, CH4), 4.87 (d, J =
14.49 Hz, 1 H, CHN), 5.06 (d, J = 14.49 Hz, 1 H, CHN), 7.20 (s, 1 H, Ar),
7.25–7.33 (m, 3 H, Ar).
13C NMR (100 MHz, CDCl3): δ = 36.64, 39.98, 46.01, 59.65, 125.51,
128.17, 128.67, 130.36, 133.06, 133.12, 194.34 (C=S).
Anal. Calcd for C11H11ClINS2: C, 34.43; H, 2.89; N, 3.65. Found: C,
34.68; H, 3.10; N, 3.44.
3-(Cyclohexylmethyl)-5-(iodomethyl)thiazolidine-2-thione (2b)
Yellow solid; yield: 0.30 g (85%); mp 82–84 °C; Rf = 0.66 (n-hexane–
EtOAc, 3:1).
3-(Furan-2-ylmethyl)-5-(iodomethyl)thiazolidine-2-thione (2j)
Yellow sticky solid; yield: 0.27 g (80%); Rf = 0.33 (n-hexane–EtOAc,
3:1).
IR (KBr): 1488, 1442, 1272, 1144, 951, 830 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.00–1.29 (m, 5 H, CH2CHCH2), 1.65–
1.87 (m, 6 H, CH2CH2CH2), 3.35 (t, J = 10.85 Hz, 1 H, CHI), 3.42–3.50
(m, 2 H), 3.73 (dd, J = 7.63, 13.43 Hz, 1 H, H4), 3.81–3.88 (m, 1 H, H5),
4.03–4.14 (m, 2 H, CH2N).
13C NMR (100 MHz, CDCl3): δ = 6.66, 24.61, 25.10, 29.64, 29.74, 35.53,
42.69, 54.18, 61.33, 193.29 (C=S).
IR (KBr): 1492, 1421, 1261, 1163, 820, 552 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.29 (t, J = 10.71 Hz, 1 H, CHI), 3.36–
3.40 (dd, J = 4.26, 10.11 Hz, 1 H, CHI), 3.79–3.85 (m, 1 H, H5), 4.02–
4.12 (m, 2 H, H4), 4.83 (d, J = 15.26 Hz, 1 H, CHN), 5.08 (d, J = 15.26 Hz,
1 H, CHN), 6.38 (s, 1 H, furyl), 6.41 (d, J = 3.03 Hz, 1 H), 7.42 (s, 1 H,
furyl).
13C NMR (100 MHz, CDCl3): δ = 6.09, 42.81, 44.30, 60.00, 109.06,
109.69, 142.10, 147.02, 193.52 (C=S).
Anal. Calcd for C11H18INS2: C, 37.18; H, 5.11; N, 3.94. Found: C, 37.36;
H, 5.30; N, 3.73.
Anal. Calcd for C9H10INOS2: C, 31.87; H, 2.97; N, 4.13. Found: C, 32.01;
H, 3.16; N, 3.95.
5-(Iodomethyl)-3-(4-isopropylbenzyl)thiazolidine-2-thione (2e)
Yellow solid; yield: 0.36 g (92%); mp 74–76 °C; Rf = 0.38 (n-hexane–
EtOAc, 3:1).
5-(Iodomethyl)-3-[(5-methylfuran-2-yl)methyl]thiazolidine-2-
thione (2k)
IR (KBr): 1494, 1414, 1254, 1176, 818, 548 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.27 (d, J = 6.92 Hz, 6 H, 2 CH3), 2.92–
2.95 (m, 1 H, CH), 3.24 (dd, J = 10.30, 10.12 Hz, 1 H, CHI), 3.38 (dd, J =
4.33, 10.12 Hz, 1 H, CHI), 3.81–3.84 (m, 1 H, H5), 3.90 (dd, J = 2.99,
12.17 Hz, 1 H, H4), 4.04 (dd, J = 7.40, 12.17 Hz, 1 H, H4), 4.89 (d, J =
14.41 Hz, 1 H, CHN), 5.04 (d, J = 14.41 Hz, 1 H, CHN), 7.25 (d, J = 8.24
Hz, 2 H, Ar), 7.29 (d, J = 8.24 Hz, 2 H, Ar).
White solid; yield: 0.29 g (83%); mp 101–103 °C; Rf = 0.34 (n-hexane–
EtOAc, 3:1).
IR (KBr): 1480, 1430, 1146, 1073, 794, 558 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.30 (s, 3 H, CH3), 3.30 (dd, J = 10.23,
11.31 Hz, 1 H, CHI), 3.38 (dd, J = 4.28, 10.14 Hz, 1 H, CHI), 3.78–3.84
(m, 1 H, H5), 4.08 (d, J = 4.70 Hz, 2 H, H4), 4.96 (d, J = 15.26 Hz, 1 H,
CHN), 5.08 (d, J = 15.26 Hz, 1 H, CHN), 5.95 (d, J = 2.24 Hz, 1 H, furyl),
6.28 (d, J = 3.06 Hz, 1 H, furyl).
13C NMR (100 MHz, CDCl3): δ = 6.42, 22.85, 32.70, 42.51, 51.28, 59.59,
126.19, 127.09, 129.65, 130.75, 193.20 (C=S).
13C NMR (100 MHz, CDCl3): δ = 6.23, 12.75, 42.84, 44.49, 59.82,
105.57, 109.99, 145.08, 152.03, 193.13 (C=S).
Anal. Calcd for C14H18INS2: C, 42.97; H, 4.64; N, 3.58. Found: C, 43.12;
H, 4.78; N, 3.34.
Anal. Calcd for C10H12INOS2: C, 34.00; H, 3.42; N, 3.97. Found: C,
34.21; H, 3.61; N, 3.80.
3-Cinnamyl-5-(iodomethyl)thiazolidine-2-thione (2f)
Yellow sticky solid; yield: 0.30 g (80%); Rf = 0.20 (n-hexane–EtOAc,
3:1).
5-(Iodomethyl)-3-(thiophen-2-ylmethyl)thiazolidine-2-thione (2l)
IR (KBr): 1487, 1438, 1249, 1168, 827 cm–1
.
Yellow solid; yield: 0.30 g (85%); mp 60–62 °C; Rf = 0.35 (n-hexane–
1H NMR (400 MHz, CDCl3): δ = 2.94 (dd, J = 3.98, 10.19 Hz, 1 H, CHI),
3.29 (dd, J = 4.67, 10.19 Hz, 1 H, CHI), 4.16–4.20 (m, 1 H, H5), 4.45 (dd,
J = 3.52, 12.04 Hz, 1 H, H4), 4.46 (dd, J = 5.13, 12.04 Hz, 1 H, H4), 4.78
(dd, J = 5.54, 13.91 Hz, 1 H, CHN), 4.94 (dd, J = 5.62, 13.91 Hz, 1 H,
CHN), 6.12–6.21 (m, 1 H, =CH), 6.64 (d, J = 15.64 Hz, 1 H, =CH), 7.28–
7.40 (m, 5 H, Ph).
EtOAc, 3:1).
IR (KBr): 1478, 1424, 1261, 1144, 1071, 563 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.24 (t, J = 10.45 Hz, 1 H, CH2I), 3.36
(dd, J = 4.35, 10.45 Hz, 1 H, CH2I), 3.78–3.84 (m, 1 H, H5), 3.98 (dd, J =
2.87, 12.02 Hz, 1 H, H4), 4.07 (dd, J = 7.25, 12.02 Hz, 1 H, H4), 5.00 (d,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 256–262

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K. D. Safa, M. Alyari
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Synthesis
J = 14.99 Hz, 1 H, CHN), 5.23 (d, J = 14.99 Hz, 1 H, CHN), 6.99 (dd, J =
3.50, 5.11 Hz, 1 H, thienyl), 7.10 (d, J = 2.91 Hz, 1 H, thienyl), 7.29 (dd,
J = 1.08, 5.11 Hz, 1 H, thienyl).
13C NMR (100 MHz, CDCl3): δ = 6.44, 42.57, 46.02, 59.35, 125.51,
1H NMR (400 MHz, CDCl3): δ = 0.15 (s, 9 H, SiMe3), 2.71 (dd, J = 9.83,
13.40 Hz, 1 H, CHS), 3.00 (dd, J = 5.20, 13.40 Hz, 1 H, CHS), 3.82–3.88
(m, 1 H, H5), 3.97 (dd, J = 3.20, 12.05 Hz, 1 H, H4), 4.06 (dd, J = 7.40,
12.05 Hz, 1 H, H4), 4.96 (d, J = 14.50 Hz, 1 H, CHN), 5.01 (d, J = 14.50
Hz, 1 H, CHN), 7.32–7.36 (m, 5 H, Ph).
13C NMR (100 MHz, CDCl3): δ = –1.21 (SiMe3), 37.94, 40.76, 51.53,
57.88, 90.55, 101.60, 127.09, 127.30, 127.94, 133.67, 194.17 (C=S).
125.85, 126.97, 135.07, 193.20 (C=S).
Anal. Calcd for C9H10INS3: C, 30.43; H, 2.84; N, 3.94. Found: C, 30.65;
H, 3.02; N, 3.76.
MS (EI, 70 eV): m/z (%) = 73 (24), 91 (100), 351 (51) [M]+.
3-Substituted 5-({[(Trimethylsilyl)ethynyl]thio}methyl)thiazoli-
dine-2-thiones 3; General Procedure
3-(4-Methylbenzyl)-5-({[(trimethylsilyl)ethynyl]thio}methyl)thi-
azolidine-2-thione (3d)
To a stirred solution of tris(trimethylsilyl)methyllithium (1 mmol) in
THF, CS2 (1.2 mmol) was added in one portion at 0 °C under an argon
atmosphere. The mixture was stirred for 15 min and then 3-substi-
tuted 5-(iodomethyl)thiazolidine-2-thione 2 (1 mmol) was added at
this temperature and stirring was maintained until the reaction was
complete (TLC). The mixture was poured into water and extracted
with CH2Cl2. The organic layer was washed with water, dried
(Na2SO4), and filtered. The solvent was removed in vacuo and the
product was purified by preparative TLC (silica gel, n-hexane–EtOAc,
3:1).
Yellow solid; yield: 0.32 g (88%); mp 60–62 °C; Rf = 0.42 (n-hexane–
EtOAc, 3:1).
IR (KBr): 2087, 1433, 1241, 1157, 1037, 880, 837, 688 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 0.15 (s, 9 H, SiMe3), 2.35 (s, 3 H, CH3),
2.69 (dd, J = 10.12, 13.27 Hz, 1 H, CHS), 3.01 (dd, J = 5.00, 13.27 Hz, 1
H, CHS), 3.78–3.87 (m, 1 H, H5), 3.96 (dd, J = 2.72, 11.96 Hz, 1 H, H4),
4.05 (dd, J = 7.35, 11.96 Hz, 1 H, H4), 4.91 (d, J = 14.38 Hz, 1 H, CHN),
4.98 (d, J = 14.38 Hz, 1 H, CHN), 7.16 (d, J = 7.66 Hz, 2 H, Ar), 7.22 (d,
J = 7.66 Hz, 2 H, Ar).
13C NMR (100 MHz, CDCl3): δ = –1.17 (SiMe3), 20.18, 37.93, 40.73,
51.39, 57.86, 90.55, 101.65, 127.18, 128.65, 130.64, 137.22, 194.04
(C=S).
5-({[(Trimethylsilyl)ethynyl]thio}methyl)thiazolidine-2-thione
(3a)
Yellow solid; yield: 0.20 g (75%); mp 100–102 °C; Rf = 0.32 (n-hexane–
EtOAc, 3:1).
MS (EI, 70 eV): m/z (%) = 73 (15), 105 (100), 365 (36) [M]+.
IR (KBr): 2093, 1505, 1459, 1244, 1169, 1026, 878, 840, 644 cm–1
.
3-(4-Isopropylbenzyl)-5-({[(trimethylsilyl)ethynyl]thio}meth-
yl)thiazolidine-2-thione (3e)
1H NMR (400 MHz, CDCl3): δ = 0.18 (s, 9 H, SiMe3), 2.94 (dd, J = 9.90,
13.42 Hz, 1 H, CHS), 3.09 (dd, J = 5.16, 13.42 Hz, 1 H, CHS), 4.03–4.06
(dd, J = 3.41, 11.66 Hz, 1 H, H4), 4.09–4.14 (dd, J = 6.95, 11.66 Hz, 1 H,
H4), 4.19–4.22 (m, 1 H, H5), 7.64 (br s, 1 H, NH).
Pale brown solid; yield: 0.35 g (90%); mp 94–96 °C; Rf = 0.38 (n-hex-
ane–EtOAc, 3:1).
IR (KBr): 2094, 14.92, 1423, 1240, 1153, 1029, 880, 845, 695 cm–1
.
13C NMR (100 MHz, CDCl3): δ = –1.15 (SiMe3), 37.65, 48.05, 53.27,
1H NMR (400 MHz, CDCl3): δ = 0.15 (s, 9 H, SiMe3), 1.24 (d, J = 6.92 Hz,
6 H, 2 CH3), 2.70 (dd, J = 9.96, 13.43 Hz, 1 H, CHS), 2.87–2.93 (m, 1 H,
CH), 3.01 (dd, J = 5.13, 13.43 Hz, 1 H, CHS), 3.81–3.87 (m, 1 H, H5),
3.97 (dd, J = 3.18, 11.62 Hz, 1 H, H4), 4.07 (dd, J = 7.33, 11.62 Hz, 1 H,
H4), 4.95 (s, 2 H, CHN), 7.21 (d, J = 7.72 Hz, 2 H, Ar), 7.25 (d, J = 7.72
Hz, 2 H, Ar).
13C NMR (100 MHz, CDCl3): δ = –1.17 (SiMe3), 22.90, 32.81, 37.98,
40.80, 51.38, 57.92, 90.65, 101.61, 126.01, 127.20, 131.02, 148.15,
194.01 (C=S).
90.59, 101.95, 194.01 (C=S).
MS (EI, 70 eV): m/z (%) = 73 (100), 261 (71) [M]+.
3-(Cyclohexylmethyl)-5-({[(trimethylsilyl)ethynyl]thio}meth-
yl)thiazolidine-2-thione (3b)
Yellow solid; yield: 0.30 g (83%); mp 102–104 °C; Rf = 0.75 (n-hexane–
EtOAc, 3:1).
IR (KBr): 2097, 1444, 1406, 1248, 1135, 1030, 879, 838, 756 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 0.17 (s, 9 H, SiMe3), 1.00–1.08 (m, 2 H,
CH2), 1.15–1.27 (m, 3 H, CHCH2), 1.64–1.85 (m, 6 H, CH2CH2CH2), 2.83
(dd, J = 10.38, 13.48 Hz, 1 H, CHS), 3.08 (dd, J = 4.85, 13.48 Hz, 1 H,
CHS), 3.56–3.68 (m, 2 H, H4), 3.87–3.91 (m, 1 H, H5), 4.13–4.22 (m, 2
H, CHN).
13C NMR (100 MHz, CDCl3): δ = –1.15 (SiMe3), 24.61, 25.11, 29.63,
29.79, 35.52, 37.95, 41.10, 54.28, 59.55, 90.66, 101.77, 193.88 (C=S).
MS (EI, 70 eV): m/z (%) = 73 (64), 133 (100), 393 (31) [M]+.
3-Cinnamyl-5-({[(trimethylsilyl)ethynyl]thio}methyl)thiazoli-
dine-2-thione (3f)
Pale brown sticky solid; yield: 0.31 g (83%); Rf = 0.19 (n-hexane–
EtOAc, 3:1).
IR (KBr): 2092, 1482, 1444, 1248, 1177, 1031, 878, 842, 694 cm–1
.
MS (EI, 70 eV): m/z (%) = 73 (91), 97 (54), 357 (100) [M]+.
1H NMR (400 MHz, CDCl3): δ = 0.16 (s, 9 H, SiMe3), 2.86 (dd, J = 3.45,
9.98 Hz, 1 H, CHS), 3.06 (dd, J = 5.11, 9.98 Hz, 1 H, CHS), 3.92–3.95 (m,
1 H, H5), 4.12 (dd, J = 3.46, 12.08 Hz, 1 H, H4), 4.23 (dd, J = 7.46, 12.08
Hz, 1 H, H4), 4.49 (dd, J = 6.90, 14.66 Hz, 1 H, CHN), 4.63 (dd, J = 6.55,
14.66 Hz, 1 H, CHN), 6.16–6.23 (m, 1 H, =CH), 6.64 (d, J = 15.81 Hz, 1
H, =CH), 7.26–7.40 (m, 5 H, Ph).
13C NMR (100 MHz, CDCl3): δ = –1.15 (SiMe3), 37.98, 40.96, 50.41,
58.36, 90.61, 101.82, 120.14, 125.58, 125.72, 127.32, 127.70, 134.40,
134.72, 193.98 (C=S).
3-Benzyl-5-({[(trimethylsilyl)ethynyl]thio}methyl)thiazolidine-2-
thione (3c)
Yellow solid; yield: 0.30 g (85%); mp 55–57 °C; Rf = 0.52 (n-hexane–
EtOAc, 3:1).
IR (KBr): 2092, 1423, 1264, 1177, 1038, 878, 842, 705 cm–1
.
MS (EI, 70 eV): m/z (%) = 73 (100), 117 (17), 377 (25) [M]+.
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3-(4-Chlorobenzyl)-5-({[(trimethylsilyl)ethynyl]thio}methyl)thi-
azolidine-2-thione (3g)
13C NMR (100 MHz, CDCl3): δ = –1.17 (SiMe3), 37.85, 41.05, 44.25,
58.25, 90.69, 101.68, 108.97, 109.68, 141.92, 147.15, 194.16 (C=S).
MS (EI, 70 eV): m/z (%) = 73 (41), 81 (100), 341 (24) [M]+.
Yellow solid; yield: 0.34 g (87%); mp 74–76 °C; Rf = 0.50 (n-hexane–
EtOAc, 3:1).
IR (KBr): 2094, 1484, 1430, 1254, 1179, 1023, 877, 840, 694 cm–1
.
3-[(5-Methylfuran-2-yl)methyl]-5-({[(trimethylsilyl)ethyn-
yl]thio}methyl)thiazolidine-2-thione (3k)
1H NMR (400 MHz, CDCl3): δ = 0.13 (s, 9 H, SiMe3), 2.68 (dd, J = 10.22,
13.17 Hz, 1 H, CHS), 2.98 (dd, J = 4.85, 13.17 Hz, 1 H, CHS), 3.79–3.87
(m, 1 H, H5), 3.93 (dd, J = 3.40, 11.78 Hz, 1 H, H4), 4.03 (dd, J = 7.62,
11.78 Hz, 1 H, H4), 4.89 (d, J = 14.67 Hz, 1 H, CHN), 4.94 (d, J = 14.67
Hz, 1 H, CHN), 7.24 (d, J = 8.02 Hz, 2 H, Ph), 7.29 (d, J = 8.02 Hz, 2 H,
Ph).
13C NMR (100 MHz, CDCl3): δ = –1.21 (SiMe3), 37.92, 40.79, 50.82,
57.93, 90.44, 101.77, 128.13, 128.52, 132.18, 133.22, 194.54 (C=S).
MS (EI, 70 eV): m/z (%) = 73 (48), 125 (100), 385 (48) [M]+.
Brown sticky solid; yield: 0.30 g (85%); Rf = 0.60 (n-hexane–EtOAc,
3:1).
IR (KBr): 2092, 1649, 1479, 1417, 1252, 1179, 1020, 878, 843, 701 cm–1
1H NMR (400 MHz, CDCl3): δ = 0.17 (s, 9 H, SiMe3), 2.27 (s, 3 H, CH3),
2.77 (dd, J = 10.36, 13.06 Hz, 1 H, CHS), 3.04 (dd, J = 4.66, 13.06 Hz, 1
H, CHS), 3.84–3.86 (m, 1 H, H5), 4.13–4.15 (m, 2 H, H4), 4.81 (d, J =
15.19 Hz, 1 H, CHN), 4.98 (d, J = 15.19 Hz, 1 H, CHN), 5.93 (s, 1 H, fu-
ryl), 6.26 (s, 1 H, furyl).
.
13C NMR (100 MHz, CDCl3): δ = –1.14 (SiMe3), 12.62, 37.89, 41.07,
44.50, 58.17, 90.75, 101.70, 105.60, 109.91, 145.29, 151.83, 193.88
(C=S).
3-(3-Chlorobenzyl)-5-({[(trimethylsilyl)ethynyl]thio}methyl)thi-
azolidine-2-thione (3h)
MS (EI, 70 eV): m/z (%) = 73 (100), 95 (31), 355 (14) [M]+.
Pale brown solid; yield: 0.31 g (80%); mp 56–58 °C; Rf = 0.51 (n-hex-
ane–EtOAc, 3:1).
IR (KBr): 2091, 1483, 1419, 1256, 1028, 876, 842, 692 cm–1
.
3-(Thiophen-2-ylmethyl)-5-({[(trimethylsilyl)ethynyl]thio}meth-
yl)thiazolidine-2-thione (3l)
1H NMR (400 MHz, CDCl3): δ = 0.10 (s, 9 H, SiMe3), 2.69 (dd, J = 9.97,
13.36 Hz, 1 H, CHS), 2.98 (dd, J = 5.12, 13.36 Hz, 1 H, CHS), 3.83–3.87
(m, 1 H, H5), 3.93 (dd, J = 2.92, 11.94 Hz, 1 H, H4), 4.02 (dd, J = 7.50,
11.94 Hz, 1 H, H4), 4.87 (d, J = 14.64 Hz, 1 H, CHN), 4.95 (d, J = 14.64
Hz, 1 H, CHN), 7.17–7.18 (m, 1 H, Ph), 7.25–7.26 (m, 3 H, Ph).
13C NMR (100 MHz, CDCl3): δ = –1.21 (SiMe3), 37.92, 40.82, 50.90,
57.94, 90.45, 101.77, 125.20, 127.13, 127.53, 129.29, 133.74, 135.66,
194.68 (C=S).
Brown sticky solid; yield: 0.30 g (85%); Rf = 0.58 (n-hexane–EtOAc,
3:1).
IR (KBr): 2090, 1536, 1479, 1438, 1254, 1136, 1043, 878, 841, 706 cm–1
1H NMR (400 MHz, CDCl3): δ = 0.16 (s, 9 H, SiMe3), 2.72 (dd, J = 10.16,
13.43 Hz, 1 H, CHS), 3.03 (dd, J = 5.03, 13.43 Hz, 1 H, CHS), 3.84–3.87
(m, 1 H, H5), 4.05–4.15 (m, 2 H, H4), 5.08 (d, J = 15.00 Hz, 1 H, CHN),
5.20 (d, J = 15.00 Hz, 1 H, CHN), 6.98 (dd, J = 3.58, 4.89 Hz, 1 H,
thienyl), 7.09 (d, J = 2.78 Hz, 1 H, thienyl), 7.28 (d, J = 4.76 Hz, 1 H,
thienyl).
.
MS (EI, 70 eV): m/z (%) = 73 (48), 125 (100), 385 (53) [M]+.
3-(Naphthalen-1-ylmethyl)-5-({[(trimethylsilyl)ethyn-
yl]thio}methyl)thiazolidine-2-thione (3i)
13C NMR (100 MHz, CDCl3): δ = –1.14 (SiMe3), 37.88, 40.86, 46.11,
57.66, 90.65, 101.73, 125.44, 125.92, 126.93, 135.40, 194.08 (C=S).
MS (EI, 70 eV): m/z (%) = 73 (89), 97 (43), 357 (100) [M]+.
Pale brown solid; yield: 0.31 g (78%); mp 101–103 °C; Rf = 0.63 (n-
hexane–EtOAc, 3:1).
IR (KBr): 2087, 1649, 1424, 1233, 1151, 1019, 879, 838, 688 cm–1
.
3-Benzyl-5-(mercaptomethyl)thiazolidine-2-thione (4)
1H NMR (400 MHz, CDCl3): δ = 0.12 (s, 9 H, SiMe3), 2.04 (dd, J = 9.84,
13.39 Hz, 1 H, CHS), 2.76 (dd, J = 5.22, 13.39 Hz, 1 H, CHS), 3.85–3.86
(m, 1 H, H5), 4.00 (dd, J = 3.25, 12.07 Hz, 1 H, H4), 4.08 (dd, J = 7.40,
12.07 Hz, 1 H, H4), 5.16 (s, 2 H, CHN), 7.45 (d, J = 8.43 Hz, 1 H, naph-
thyl), 7.51 (t, J = 4.47 Hz, 2 H, naphthyl), 7.77 (s, 1 H, naphthyl), 7.82–
7.86 (m, 3 H, naphthyl).
13C NMR (100 MHz, CDCl3): δ = –1.19 (SiMe3), 38.05, 40.87, 51.87,
58.04, 90.68, 101.93, 124.62, 125.45, 125.60, 126.44, 126.79, 128.10,
131.29, 132.11, 132.25, 194.08 (C=S).
Yellow sticky solid; Rf = 0.26 (n-hexane–EtOAc, 3:1).
IR (KBr): 2090, 1536, 1479, 1438, 1254, 1136, 1043, 878, 841, 706 cm–1
1H NMR (400 MHz, CDCl3): δ = 1.51 (t, J = 8.80 Hz, 1 H, SH), 2.58–2.65
(m, 1 H, CHSH), 2.74–2.81 (m, 1 H, CHSH), 3.58–3.64 (m, 1 H, H5),
3.84–3.88 (dd, J = 3.36, 11.97 Hz, 1 H, H4), 4.00–4.05 (dd, J = 7.67,
11.97 Hz, 1 H, H4), 4.84 (d, J = 14.50 Hz, 1 H, CHN), 5.11 (d, J = 14.50
Hz, 1 H, CHN), 7.32–7.40 (m, 5 H, Ph).
13C NMR (100 MHz, CDCl3): δ = 28.22, 44.62, 51.55, 58.06, 127.18,
127.36, 128.00, 133.85, 194.34 (C=S).
MS (EI, 70 eV): m/z (%) = 91 (86), 148 (100), 255 (81) [M]+.
.
MS (EI, 70 eV): m/z (%) = 73 (63), 141 (100), 401 (27) [M]+.
3-(Furan-2-ylmethyl)-5-({[(trimethylsilyl)ethynyl]thio}meth-
yl)thiazolidine-2-thione (3j)
Supporting Information
Brown sticky solid; yield: 0.28 g (82%); Rf = 0.48 (n-hexane–EtOAc,
3:1).
Supporting information for this article is available online at
IR (KBr): 2092, 1511, 1457, 1421, 1263, 1168, 1027, 878, 842, 703 cm–1
.
http://dx.doi.org/10.1055/s-0034-1379253.
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1H NMR (400 MHz, CDCl3): δ = 0.16 (s, 9 H, SiMe3), 2.76 (dd, J = 10.00,
13.43 Hz, 1 H, CHS), 3.03 (dd, J = 5.08, 13.43 Hz, 1 H, CHS), 3.83–3.89
(m, 1 H, H5), 4.10–4.18 (m, 2 H, H4), 4.91 (d, J = 15.24 Hz, 1 H, CHN),
5.01 (d, J = 15.24 Hz, 1 H, CHN), 6.35–6.36 (t, J = 2.52 Hz, 1 H, furyl),
6.39 (d, J = 3.11 Hz, 1 H, furyl), 7.39 (d, J = 1.00 Hz, 1 H, furyl).
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