Synthesis of novel 2-thienylimino-1,3-thiazolidin-4-ones

Article abstract of DOI:10.1055/s-0029-1218780

The preparation of new 2-thienylimino-1,3-thiazolidin-4-ones from 3-aminothiophene-2-carboxylate using an easy four-step procedure is described. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1218780

PAPER
2543
Synthesis of Novel 2-Thienylimino-1,3-thiazolidin-4-ones
S
ynthesi
s
s
of
N
ove
m
l
2-Thienylimino-1,
a
3-thiazolidi
i
n-4-on
l
Laboratoire d’Ingénierie Moléculaire et Biochimie Pharmacologique, Institut Jean Barriol, FR CNRS 2843, 1 Boulevard Arago,
57070 Metz, France
Fax +33(3)87325801; E-mail: kirsch@.univ-metz.fr
Received 19 March 2010; revised 31 March 2010
Dedicated to Professor Jan Bergman on the occasion of his retirement
The various aminothiophene carboxylates were first sa-
ponified by refluxing with a solution of potassium hy-
droxide for four hours, and the amino acids obtained were
decarboxylated using anhydrous oxalic acid14 with excel-
lent yields. We also observed that the decarboxylation of
these compounds may occur during the saponification, in
particular with the 3-amino-5-(tert-butyl)-2-thiophene-
carboxylic acid, which will therefore not be described
here. The chloroacetamides were then synthesized by
reaction between the thiophenamines and chloroacetyl
chloride in N,N-dimethylformamide. The target thiazolid-
inones were finally reached by heating chloroacetamides
and ammonium thiocyanate in ethanol at reflux for three
hours (Scheme 3; Table 1). The cyclization mechanism
has already been described by Vicini.3
Abstract: The preparation of new 2-thienylimino-1,3-thiazolidin-
4-ones from 3-aminothiophene-2-carboxylate using an easy four-
step procedure is described.
Key words: 3-aminothiophene-2-carboxylate, ammonium thiocy-
anate, 2-thienylimino-1,3-thiazolidin-4-ones
In continuation of our synthetic work with 3-amino-2-
substituted thiophenes previously developed in our labo-
ratory,1 we propose here a new route to 2-thienylimino-
1,3-thiazolidin-4-ones. The synthesis has been devised to
use this kind of heterocycle as a scaffold for preparing
new biologically active compounds.
2-Heteroarylimino-1,3-thiazolidin-4-ones, in particular
thiazolimino- and benzothiazolimino-types, have previ-
ously been described in the literature and used as scaffolds
for preparing a range of antifungal and antibacterial com-
pounds,2–4 however, derivatives bearing a substituted
thiophene as the aromatic ring are not yet known. We de-
scribe here their preparation from ethyl or methyl 3-ami-
nothiophene-2-carboxylate, as shown in Scheme 1.
R2
R1
NH2
R2
R1
NH2
i
CO2R3
CO2H
S
S
1a–f
2a–f
ii
H
N
O
R2
R1
NH2
R2
R1
R2
R1
NH2
R2
H
iii
N
N
O
Cl
S
R1
CO2R3
S
S
S
S
4a–f
3a–f
Scheme 1 Synthesis of 2-thienylimino-1,3-thiazolidin-4-ones
iv
The aminothiophene esters (1a–f) were synthesized from
b-chloropropenonitrile, which was obtained from b-chlo-
ropropenal as previously described (Scheme 2).5–13
H
N
R2
H
N
R2
N
N
O
O
S
S
R1
R1
S
S
5'a–f
5a–f
R1
R2
O
R1
R2
Cl
R1
R2
S
iv
i–iii
CO2R3
Scheme 3 Reagents and conditions: (i) KOH, EtOH or MeOH, re-
flux, 4 h; (ii) Anhydrous oxalic acid, i-PrOH, 40 °C; (iii) ClCOCH2Cl,
anhydrous DMF, r.t., 2 h; (iv) NH4SCN, EtOH, reflux, 3 h.
CN
NH2
1a–f
Thiazolidinone 5 could exist in the tautomeric form 5¢,
however, a 1H NMR study led us to consider that 5 is the
only form existing. First, the high value of the shift of the
NH proton led us to assume that the proton is in the vicin-
ity of the carbonyl. Furthermore, the signal corresponding
to the CH2 from the thiazolidinone ring appears as a dou-
blet because of coupling with the NH, which is only pos-
sible in the first form. Finally, HMBC analysis showed
that the hydrogen from the NH is only correlated with the
Scheme 2 Reagents and conditions: (i) POCl3, DMF, 60 °C, 5 h; (ii)
hydroxylamine chloride, EtOH; (iii) Ac2O; (iv) HSCH2CO2Et/Me,
K2CO3, DMF.
SYNTHESIS 2010, No. 15, pp 2543–2546
x
x.
x
x
.
2
0
1
0
Advanced online publication: 05.05.2010
DOI: 10.1055/s-0029-1218780; Art ID: Z07410SS
© Georg Thieme Verlag Stuttgart · New York

2544
I. Abdillahi et al.
PAPER
1H NMR (250 MHz, DMSO-d6): d = 6.78 (s, 1 H, CH), 7.39–7.41
(m, 3 H, 3 × CH), 7.59–7.61 (m, 2 H, 2 × CH).
13C NMR (62.9 MHz, DMSO-d6): d = 98.14, 116.20, 125.43,
128.90, 129.14, 132.92, 146.72, 155.04, 165.23.
CH2 carbon atom, and not with the aromatic carbon atoms
from the thiophene ring, thus reinforcing the idea that the
first form is favored.
Table 1 2-Thienylimino-1,3-tiazolidin-4-one Yields
3-Amino-5-(4-methylphenyl)-2-thiophenecarboxylic Acid (2b)
Yield: 88%; pale-brown solid; mp 184 °C.
1H NMR (250 MHz, DMSO-d6): d = 2.28 (s, 3 H, CH3), 6.88 (s,
1 H, CH), 7.21 (d, J = 8 Hz, 2 H, 2 × CH), 7.47 (d, J = 8 Hz, 2 H, 2
× CH).
13C NMR (62.9 MHz, DMSO-d6): d = 20.64, 96.82, 117.08, 124.59,
129.59, 131.35, 137.08, 141.51, 146.82, 162.09.
Thiophene 1
Thiazolidinone 5
Yield
(%)
H
NH2
N
N
O
58
48
Ph
S
S
Ph
S
CO2Et
5a
H
N
NH2
3-Amino-5-(4-chlorophenyl)-2-thiophenecarboxylic Acid (2c)
Yield: 70%; pale-brown solid; mp 146 °C.
1H NMR (250 MHz, DMSO-d6): d = 6.96 (s, 1 H, CH), 7.48 (d, J =
8.5 Hz, 2 H, 2 × CH), 7.91 (d, J = 8.5 Hz, 2 H, 2 × CH).
13C NMR (62.9 MHz, DMSO-d6): d = 116.77, 127.17, 129.14,
131.83, 133.34, 145.06, 154.94, 165.21.
N
O
O
MeC6H4
S
S
S
MeC6H4
CO2Et
NH2
S
5b
H
N
N
46
90
55
ClC6H4
S
ClC6H4
CO2Et
NH2
S
3-Amino-5-(4-methoxyphenyl)-2-thiophenecarboxylic Acid
(2d)
Yield: 83%; pale-brown solid; mp 142 °C.
1H NMR (250 MHz, DMSO-d6): d = 3.77 (s, 3 H, OCH3), 6.83 (s,
1 H, CH), 6.97 (d, J = 8.75 Hz, 2 H, 2 × CH), 7.53 (d, J = 8.75 Hz,
2 H, 2 × CH).
13C NMR (62.9 MHz, DMSO-d6): d = 55.23, 114.50, 125.61,
125.98, 126.96, 146.65, 154.96, 159.79, 165.40.
5c
H
N
N
O
MeOC6H4
S
S
MeOC6H4
CO2Me
S
5d
H
N
NH2
N
O
t-Bu
S
S
t-Bu
CO2Et
S
3-Amino-5,-6-dihydronaphtho[2¢,1¢,4,5]-2-thiophenecarboxyl-
ic Acid (2f)
Yield: 80%; green solid; mp 153 °C.
1H NMR (250 MHz, DMSO-d6): d = 2.60–2.63 (m, 2 H, CH2),
2.85–2.91 (m, 2 H, CH2), 7.18–7.20 (m, 3 H, 3 × CH), 7.27–7.32
(m, 1 H, CH).
5e
H
N
O
NH2
N
S
77
CO2Et
S
S
13C NMR (62.9 MHz, DMSO-d6): d = 20.44, 28.12, 97.73, 123.03,
127.02, 127.72, 128.16, 128.35, 130.10, 135.45, 138.92, 152.50,
165.80.
5f
The thiazolidinone scaffold will be used for structural
modification on the nitrogen atom, and we intend to use
the reactivity of the CH2 group to introduce further diver-
sity into the series.
Synthesis of Thiophenamines (3a–f); General Procedure
To a stirred solution of the appropriate aminothiophenecarboxylic
acid (20 mmol) in i-PrOH (20 mL) was added anhydrous oxalic acid
(1 equiv). The reaction was stirred at 40 °C until CO2 evolution sub-
sided. The mixture was cooled to r.t. and Et2O (30 mL) was added.
The precipitate was filtered, washed with petroleum ether (2 × 10
mL) and dried.
Melting points were determined with a Stuart SMP3 apparatus and
1
are uncorrected. H and 13C NMR spectra were recorded with a
Bruker AC 250 MHz spectrometer in either CDCl3 or DMSO-d6.
Mass spectra were recorded with a MicroTof-Q 98. IR spectra were
recorded with a Perkin–Elmer FTIR Baragon 1000PC instrument
equipped with Spectrum (Perkin–Elmer) software version 5.3.1.
5-Phenyl-3-thiophenamine (3a)
Yield: 99%; pale-brown solid; mp 164 °C.
1H NMR (250 MHz, DMSO-d6): d = 6.05 (d, J = 1.5 Hz, 1 H, CH),
6.96 (d, J = 1.5 Hz, 1 H, CH), 7.26 (t, J = 7.25 Hz, 1 H, CH), 7.36
(t, J = 7.25 Hz, 2 H, 2 × CH), 7.51 (d, J = 7.25 Hz, 2 H, 2 × CH).
13C NMR (62.9 MHz, DMSO-d6): d = 97.19, 117.55, 124.66,
127.25, 128.97, 134.07, 141.33, 147.12, 161.25.
Synthesis of Aminothiophenecarboxylic Acids (2a–f); General
Procedure
To a stirred solution of the appropriate thiophene (30 mmol) in
EtOH or MeOH (30 mL) was added a solution of KOH (4 equiv) in
H2O (15 mL). The mixture was heated at reflux for 4 h and then the
solvent was evaporated. The residue was poured into H2O (45 mL)
and acidified to neutral pH with orthophosphoric acid. The precipi-
tate was filtered, washed with H2O (2 × 10 mL) and petroleum ether
(2 × 10 mL) and dried.
5-(4-Methylphenyl)-3-thiophenamine (3b)
Yield: 98%; pale-brown solid; mp 167 °C.
1H NMR (250 MHz, DMSO-d6): d = 2.27 (s, 3 H, CH3), 6.01 (s,
1 H, CH), 6.90 (s, 1 H, CH), 7.17 (d, J = 8.2 Hz, 2 H, 2 × CH), 7.40
(d, J = 8.2 Hz, 2 H, 2 × CH).
13C NMR (62.9 MHz, DMSO-d6): d = 20.62, 95.55, 116.99, 124.14,
129.48, 131.40, 136.58, 141.33, 147.91.
3-Amino-5-phenyl-2-thiophenecarboxylic Acid (2a)
Yield: 81%; pale-brown solid; mp 103 °C.
Synthesis 2010, No. 15, 2543–2546 © Thieme Stuttgart · New York

PAPER
Synthesis of Novel 2-Thienylimino-1,3-thiazolidin-4-ones
2545
5-(4-Chlorophenyl)-3-thiophenamine (3c)
Yield: 97%; pale-brown solid; mp 196 °C.
2-Chloro-N-[5-(4-chlorophenyl)-3-thienyl]acetamide (4c)
Yield: 88%; brown solid; mp 135 °C.
1H NMR (250 MHz, DMSO-d6): d = 6.03 (s, 1 H, CH), 6.96 (s, 1 H,
CH), 7.41 (d, J = 8.5 Hz, 2 H, 2 × CH), 7.53 (d, J = 8.5 Hz, 2 H, 2
× CH).
13C NMR (62.9 MHz, DMSO-d6): d = 97.14, 118.03, 126.28,
128.93, 133.01, 139.77, 147.74, 162.
IR (KBr): 3255 (NH), 1647 (C=O) cm–1.
1H NMR (250 MHz, DMSO-d6): d = 4.24 (s, 2 H, CH2), 7.43–7.48
(m, 3 H, 3 × CH), 7.55–7.63 (m, 3 H, 3 × CH), 10.73 (s, 1 H, NH).
13C NMR (62.9 MHz, DMSO-d6): d = 43.33, 109.95, 117.92,
126.62, 129.13, 132.18, 132.31, 136.7, 140.22, 164.02.
HRMS (APCI): m/z [C12H9Cl2NOS + H]+ calcd: 285.9855; found:
285.9862.
5-(4-Methoxyphenyl)-3-thiophenamine (3d)
Yield: 98%; pale-green solid; mp 216 °C.
1H NMR (250 MHz, DMSO-d6): d = 3.77 (s, 3 H, CH3), 5.92 (d,
J = 1.5 Hz, 1 H, CH), 6.81 (d, J = 1.5 Hz, 1 H, CH), 6.93 (d, J =
7.25 Hz, 2 H, 2 × CH), 7.44 (d, J = 7.25 Hz, 2 H, 2 × CH).
13C NMR (62.9 MHz, DMSO-d6): d = 55.12, 95.46, 114.33, 116.5,
126, 126.9, 141.28, 147.38, 158.59, 161.94.
2-Chloro-N-[5-(4-methoxyphenyl)-3-thienyl]acetamide (4d)
Yield: 62%; pale-brown solid; mp 138 °C.
IR (KBr): 3287 (NH), 1658 (C=O) cm–1.
1H NMR (250 MHz, DMSO-d6): d = 3.76 (s, 3 H, CH3), 4.21 (s,
2 H, CH2), 6.97 (d, J = 8.75 Hz, 2 H, 2 × CH), 7.27 (s, 1 H, CH),
7.43 (s, 1 H, CH), 7.50 (d, J = 8.75 Hz, 2 H, 2 × CH ), 10.70 (s, 1 H,
NH).
13C NMR (62.9 MHz, DMSO-d6): d = 42.97, 61.56, 108.24, 114.52,
116.2, 125.96, 126.58, 136.67, 141.68, 159.06, 170.31.
5-tert-Butyl-3-thiophenamine (3e)
Yield: 52%; green solid; mp 145 °C.
1H NMR (250 MHz, DMSO-d6): d = 1.25 (s, 9 H, 3 × CH3), 5.93 (s,
1 H, CH), 6.41 (s, 1 H, CH).
13C NMR (62.9 MHz, DMSO-d6): d = 31.6, 33.9, 95.2, 116.2,
141.4, 154.7.
HRMS (APCI): m/z [C13H12ClNO2S + H]+ calcd: 282.0350; found:
282.0356.
2-Chloro-N-(5-tert-butyl-3-thienyl)acetamide (4e)
Yield: 77%; pale-brown solid; mp 136 °C.
IR (KBr): 3278 (NH), 1648 (C=O) cm–1.
1H NMR (250 MHz, DMSO-d6): d = 1.28 (s, 9 H, 3 × CH3), 4.16 (s,
2 H, CH2), 6.84 (s, 1 H, CH), 7.28 (s, 1 H, CH), 10.53 (s, 1 H, NH).
5,6-Dihydronaphtho[2¢,1¢,4,5]-3-thiophenamine (3f)
Yield: 90%; green solid; mp 168 °C.
1H NMR (250 MHz, DMSO-d6): d = 2.55 (t, J = 7.5 Hz, 2 H, CH2),
2.84 (t, J = 7.5 Hz, 2 H, CH2), 6.02 (s, 1 H, CH), 7.08–7.21 (m, 4 H,
4 × CH).
13C NMR (62.9 MHz, DMSO-d6): d = 21, 28.1, 96.1, 121.8, 126.5,
126.8, 127.9, 129.4, 131.4, 134.1, 144.5, 161.6.
13C NMR (62.9 MHz, DMSO-d6): d = 33.9, 38.7, 43, 106.5, 116.1,
134.9, 155.2, 163.7.
HRMS (APCI): m/z [C10H14ClNOS + H]+ calcd: 232.0557; found:
232.0564.
Synthesis of 2-Chloro-N-thienylacetamides (4a–f); General
Procedure
To a stirred solution of the appropriate aminothiophene (10 mmol)
in anhydrous DMF (15 mL) was added dropwise using a syringe,
chloroacetyl chloride (1.1 equiv). The mixture was stirred at 25 °C
for 2 h and then poured into H2O. The precipitate was filtered,
washed with H2O (2 × 10 mL) and petroleum ether (2 × 10 mL) and
dried.
2-Chloro-N-(5,6-dihydronaphtho[2¢,1¢,4,5]-3-thienyl)acet-
amide (4f)
Yield: 73%; green solid; mp 146 °C.
IR (KBr): 3276 (NH), 1653 (C=O) cm–1.
1H NMR (250 MHz, DMSO-d6): d = 2.73 (d, J = 7.5 Hz, 2 H, CH2),
2.88 (d, J = 7.5 Hz, 2 H, CH2), 4.34 (s, 2 H, CH2), 7.18–7.31 (m,
4 H, 4 × CH), 7.60 (s, 1 H, CH), 9.96 (s, 1 H, NH).
13C NMR (62.9 MHz, DMSO-d6): d = 21.4, 27.9, 43, 110.7, 122.2,
127, 127.2, 128, 130.6, 133.7, 133.8, 133.9, 134.3, 164.6.
2-Chloro-N-(5-phenyl-3-thienyl)acetamide (4a)
Yield: 71%; pale-brown solid; mp 128 °C.
IR (KBr): 3271 (NH), 1651 (C=O) cm–1.
1H NMR (250 MHz, DMSO-d6): d = 4.24 (s, 2 H, CH2), 7.31 (t, J =
7.5 Hz, 1 H, CH), 7.41 (t, J = 7.5 Hz, 3 H, 3 × CH ), 7.57 (t, J =
7.5 Hz, 3 H, 3 × CH ), 10.71 (s, 1 H, NH).
HRMS (APCI): m/z [C14H12ClNOS + H]+ calcd: 278.0401; found:
278.0414.
13C NMR (62.9 MHz, DMSO-d6): d = 43.01, 109.40, 117.34,
Synthesis of Thiazolidinones (5a–f): General Procedure
To a stirred solution of the appropriate acetamide (5 mmol) in EtOH
(20 mL) was added ammonium thiocyanate (1 equiv). The mixture
was heated at reflux for 3 h and allowed to stand overnight. The pre-
cipitate was filtered, washed with H2O (2 × 10 mL) and petroleum
ether (2 × 10 mL) and dried.
125.07, 127.91, 129.17, 133.27, 136.61, 141.65, 163.97.
HRMS (APCI): m/z [C12H10ClNOS + H]+ calcd: 252.0244; found:
252.0254.
2-Chloro-N-[5-(4-methylphenyl)-3-thienyl]acetamide (4b)
Yield: 56%; green solid; mp 121 °C.
IR (KBr): 3285 (NH), 1653 (C=O) cm–1.
2-[(5-Phenyl-3-thienyl)imino]-1,3-thiazolidin-4-one (5a)
Yield: 58%; pale-brown solid; mp 197 °C.
1H NMR (250 MHz, DMSO-d6): d = 2.37 (s, 3 H, CH3), 4.21 (s,
2 H, CH2), 7.17–7.20 (m, 2 H, 2 × CH), 7.24–7.26 (m, 1 H, CH),
7.45–7.48 (m, 2 H, 2 × CH), 8.49 (s, 1 H, NH).
13C NMR (62.9 MHz, DMSO-d6): d = 20.7, 43, 108.8, 116.8, 125,
129.7, 130.7, 136.4, 136.5, 141.8, 163.9.
HRMS (APCI): m/z [C13H12ClNOS + H]+ calcd: 266.0401; found:
266.0400.
IR (KBr): 3060 (NH), 1602 (C=O) cm–1.
1H NMR (250 MHz, DMSO-d6): d = 4.01 (d, J = 9.5 Hz, 2 H, CH2),
7.01 (s, 1 H, CH), 7.27–7.46 (m, 4 H, 4 × CH), 7.58–7.63 (m, 2 H,
2 × CH), 11.55 (s, 1 H, NH).
13C NMR (62.9 MHz, DMSO-d6): d = 34.95, 111.29, 117.49,
120.29, 124.99, 129.11, 133.06, 136.98, 142.26, 177.54, 187.96.
Synthesis 2010, No. 15, 2543–2546 © Thieme Stuttgart · New York

2546
I. Abdillahi et al.
PAPER
HRMS (APCI): m/z [C13H10N2OS2 + H]+ calcd: 275.0307; found:
275.0312.
13C NMR (62.9 MHz, DMSO-d6): d = 32.09, 34.1, 108.5, 116.2,
118.8, 135.4, 156, 171, 187.86.
HRMS (ESI): m/z [C11H14N2OS2 + Na]+ calcd: 277.0440; found:
277.0440.
2-{[5-(4-Methylphenyl)-3-thienyl]imino}-1,3-thiazolidin-4-one
(5b)
Yield: 48%; green solid; mp 250 °C.
IR (KBr): 2919 (NH), 1614 (C=O) cm–1.
2-{(5,6-Dihydronaphtho[2¢,1¢,4,5]-3-thienyl)imino}-1,3-thiazo-
lidin-4-one (5f)
Yield: 74%; green solid; mp 100 °C.
IR (KBr): 2970 (NH), 1633 (C=O) cm–1.
1H NMR (250 MHz, DMSO-d6): d = 2.57 (t, J = 7.5 Hz, 2 H, CH2),
2.87 (t, J = 7.5 Hz, 2 H, CH2), 3.98 (d, J = 9.5 Hz, 2 H, CH2), 6.93
(s, 1 H, CH), 7.13–7.35 (m, 4 H, 4 × CH), 11.76 (s, 1 H, NH).
1H NMR (250 MHz, DMSO-d6): d = 2.30 (s, 3 H, CH3), 4.01 (d,
J = 9.5 Hz, 2 H, CH2), 6.96 (s, 1 H, CH), 7.19–7.24 (m, 2 H, 2 ×
CH), 7.41–7.55 (m, 3 H, 3 × CH), 11.53 (s, 1 H, NH).
13C NMR (62.9 MHz, DMSO-d6): d = 20.7, 34.92, 110.7, 117,
119.7, 125, 129.7, 130.5, 137.5, 142.4. 177.4, 187.8.
HRMS (APCI): m/z [C14H12N2OS2 + H]+ calcd: 289.0464; found:
289.0474.
13C NMR (62.9 MHz, DMSO-d6): d = 21.56, 28.04, 34.71, 121.99,
122.15, 127.02, 127.19, 128.12, 130.77, 132.82, 134.24, 134.43,
134.86, 175.74.
2-{[5-(4-Chlorophenyl)-3-thienyl]imino}-1,3-thiazolidin-4-one
(5c)
Yield: 46%; pale-brown solid; mp 280 °C.
HRMS (ESI): m/z [C15H12N2OS2 + Na]+ calcd: 323.0283; found:
323.0281.
IR (KBr): 3119 (NH), 1619 (C=O) cm–1.
Acknowledgment
1H NMR (250 MHz, DMSO-d6): d = 4.02 (d, J = 9.5 Hz, 2 H, CH2),
7.03 (s, 1 H, CH), 7.30 (s, 1 H, CH), 7.43–7.49 (m, 2 H, 2 × CH),
7.61–7.65 (m, 2 H, 2 × CH), 11.67 (s, 1 H, NH).
I.A. thanks EGIDE for financial support. We are grateful to V.
Poddig for NMR studies and A. Crepet for IR analysis.
13C NMR (62.9 MHz, DMSO-d6): d = 39.63, 111.83, 120.97,
126.84, 129.16, 131.98, 132.50, 137.06, 141.30, 177.77, 187.92.
HRMS (APCI): m/z [C13H9ClN2OS2 + H]+ calcd: 308.9918; found:
References
(1) (a) Hesse, S.; Perspicace, E.; Kirsch, G. Tetrahedron Lett.
2007, 48, 5261. (b) Thomae, D.; Kirsch, G.; Seck, P.
Synthesis 2007, 2153.
(2) Omar, K.; Geronikaki, A.; Zoumpoulakis, P.; Camoutsis, C.;
Sokovic, M.; Ciric, C.; Glamoclija, J. Bioorg. Med. Chem.
2010, 18, 426.
(3) Vicini, P.; Geronikaki, A.; Anastasia, K.; Incerti, M.; Zani,
F. Bioorg. Med. Chem. 2006, 14, 3859.
(4) Vicini, P.; Geronikaki, A.; Incerti, M.; Zani, F.; Dearden, J.;
Hewitt, M. Bioorg. Med. Chem. 2008, 16, 3714.
(5) (a) Vilsmeier, A.; Haack, A. A. Ber. Dtsch. Chem. Ges.
1927, 60, 119. (b) Arnold, Z.; Sorm, F. Collect. Czech.
Chem. Commun. 1958, 23, 452.
308.9925.
2-{[5-(4-Methoxyphenyl)-3-thienyl]imino}-1,3-thiazolidin-4-
one (5d)
Yield: 90%; orange solid; mp 219 °C.
IR (KBr): 3102 (NH), 1610 (C=O) cm–1.
1H NMR (250 MHz, DMSO-d6): d = 3.76 (s, 3 H, CH3), 4.02 (d,
J = 9.5 Hz, 2 H, CH2), 6.92–7.00 (m, 2 H, 2 × CH), 7.14 (s, 1 H,
CH), 7.33 (s, 1 H, CH), 7.51–7.56 (m, 2 H, 2 × CH), 11.75 (s, 1 H,
NH).
13C NMR (62.9 MHz, DMSO-d6): d = 18.45, 55.18, 110.12, 114.47,
119.07, 126.07, 126.53, 136.77, 142.31, 159.06, 177.47, 187.98.
(6) Ren, W.-Y.; Rao, K.; Kein, R. J. Heterocycl. Chem. 1986,
23, 1757.
HRMS (ESI): m/z [C14H12N2O2S2 + Na]+ calcd: 327.0232; found:
327.0247.
(7) Vega, S.; Gil, M. S. J. Heterocycl. Chem. 1991, 28, 1757.
(8) Hartmann, H.; Liebscher, J. Synthesis 1984, 275.
(9) Hartmann, H.; Liebscher, J. Synthesis 1984, 276.
(10) Liebscher, J.; Neumann, B.; Hartmann, H. J. Prakt. Chem.
1983, 325, 915.
2-[(5-tert-Butyl-3-thienyl)imino]-1,3-thiazolidin-4-one (5e)
Yield: 55%; green solid; mp 167 °C.
IR (KBr): 2955 (NH), 1603 (C=O) cm–1.
(11) Hartmann, H.; Liebscher, J. Synthesis 1979, 241.
(12) Migianu, E.; Kirsch, G. Synthesis 2002, 1096.
(13) Thomae, D.; Kirsch, G.; Seck, S. Synthesis 2007, 1027.
(14) Barker, J. M.; Wood, M. L.; Huddleston, P. R. Synth.
Commun. 1995, 5, 3729.
1H NMR (250 MHz, DMSO-d6): d = 1.30 (s, 9 H, 3 × CH3), 4.00 (d,
J = 9.5 Hz, 2 H, CH2), 6.96 (s, 1 H, CH), 7.42 (s, 1 H, CH), 11.35
(s, 1 H, NH).
Synthesis 2010, No. 15, 2543–2546 © Thieme Stuttgart · New York