Novel (4-oxothiazolidine-2-ylidene)benzamide derivatives: synthesis, characterization and crystal structures

Article abstract of DOI:10.1007/s11164-017-2872-0

A convenient, one-pot, multicomponent synthesis of new (4-oxothiazolidine-2-ylidene)benzamide derivatives by unsymmetrical thioureas, various amines and methyl bromoacetate has been developed. These new compounds were characterized by IR, ¹HNMR

Full text of DOI:10.1007/s11164-017-2872-0

Res Chem Intermed
DOI 10.1007/s11164-017-2872-0
Novel (4-oxothiazolidine-2-ylidene)benzamide
derivatives: synthesis, characterization and crystal
structures
Mahshid Hossaini1 Reza Heydari1
•
•
Malek Taher Maghsoodlou1 Claudia Graiff2
•
Received: 28 July 2016 / Accepted: 17 January 2017
Ó Springer Science+Business Media Dordrecht 2017
Abstract A convenient, one-pot, multicomponent synthesis of new (4-oxothiazo-
lidine-2-ylidene)benzamide derivatives by unsymmetrical thioureas, various amines
and methyl bromoacetate has been developed. These new compounds were char-
1
acterized by IR, HNMR, 13CNMR, mass spectrometry, CHNS elemental analysis,
and single-crystal X-ray analysis.
Keywords (4-Oxothiazolidin-2-ylidene)benzamide Á Amine Á Thioureas Á
Methyl bromoacetate Á Multi-component reactions (MCRs)
Introduction
The design and the synthesis of new drugs based on combinations of hybrid
molecules are one of the important methods in modern chemistry. These compounds
are synthesized by combining various pharmacophore fragments, and the obtained
products have interesting biological activity.
Thiazoles and their derivatives have a heterocyclic ring containing nitrogen and
sulphur. These compounds are important scaffolds in chemistry and have been
found in the structure of many drugs because they have various biological properties
[1], such as anticancer [2, 3], antifungal [4], anti-inflammatory [5], antibacterial
[6, 7], anticonvulsant [8], antidiabetic [9] and anti-HIV [10]. On the other hand,
amides are known as important components in supramolecular chemical anion
&
Reza Heydari
heydari@chem.usb.ac.ir
1
2
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan,
PO Box 98135-674, Zahedan, Iran
´
Dipartimento di Chimica, Universita di Parma, Viale delle Scienze 17/A
Campus Universitario, 43100 Parma, Italy
123

M. Hossaini et al.
sensors. Furthermore, amides can be selectively connected via hydrogen bonds to
anionic substrates, such as DNA, and reveal new biological properties [11].
In general, thiazoles are synthesized by Hantzsch synthesis [12], where the
cyclization of a-halocarbonyl compounds is carried out with a great variety of
reactants including thioamides and thioureas. In recent decades, several methods
have been reported to produce thiazole derivatives, such as the cyclization of
thioureas with acetylenedicarboxylates or phenacyl bromide [13], the reaction
between isothiocyanatobenzene and 1, 4-dithiane-2, 5-diol [14], and the cyclocon-
densation of thionyl chloride with enaminones [15]. Other methods include
reactions of amines with benzaldehyde and an excess of mercaptoacetic acid in the
¨
presence of different catalysts [16–18]. Domling et al. have also reported
multicomponent reactions (MCRs) by using special isocyanide, thiocarboxylic
acid, aldehyde and a primary amine for the synthesis of these compounds [19].
The thiazole derivatives containing amide groups may have interesting proper-
ties. Reactions of amine with ethyl cyanoacetate and aryl isothiocyanate have been
reported to produce new compounds such as dual anti-inflammatory and antimi-
crobial agents [20]. Shahvelayati et al. used a-amino acids, aroyl isothiocyanates,
and a-bromoketones in an ionic liquid [21]. The synthesis of these compounds by
reactions between acetohydrazide derivatives and aldehyde with mercaptoacetic
acid has also been investigated [22, 23].
In this paper, we describe an efficient one-pot method for the synthesis of some
(4-Oxothiazolidine-2-ylidene) benzamide derivatives via condensation benzoyl
isothiocyanate derivatives, suitable heterocyclic (aromatic) amines and methyl
bromoacetate.
Experimental
Methods and materials
The reagents and solvents were purchased from Merck and Aldrich Chemical
companies and were used as received. The samples were analyzed by FT-IR
spectroscopy (JASCO FT/IR-460 plus spectrometer) and melting points were
1
detected by Electro thermal 9100 apparatus. H NMR and 13C NMR spectra were
recorded on a Bruker DRX-400 Avance instrument in CDCl3. The mass spectra
were recorded on an Agilent Technology HP 5973 MSD mass spectrometer
operating at an ionization potential of 70 eV, and elemental analyses were
performed using a Heraeus CHN-Rapid analyzer.
General procedure for the synthesis of (4-oxothiazolidine-2-ylidene)
benzamide derivatives
A mixture of 1 mmol benzoyl isothiocyanate derivatives (1) and 1.0 mmol
appropriate (hetero) aromatic amine (2) in 5 ml acetonitrile as solvent under reflux
conditions was stirred. Then, methyl bromoacetate (3) (1.1 mmol) and triethylamine
(1.0 mmol, 0.10 g) were added to the reaction mixture. The progress of the reaction
123

Novel (4-oxothiazolidine-2-ylidene)benzamide derivatives:…
was monitored by thin-layer chromatography (TLC). The reaction mixture was
cooled to room temperature and microcrystalline powder was filtered and washed
with a small amount of cold ethanol, and then recrystallized from suitable solvents.
Spectral data
(Z)-N-(3-(furan-2-ylmethyl)-4-oxothiazolidine-2-ylidene)benzamide (4a) Brown
solid; Yield = 86%, m.p. = 199–201 °C; IR (KBr): 3003, 3051 (C–H aromatic),
2976 (C–H aliphatic), 1737 (C=O), 1642 (C=O thiazol), 1596, 1448, 1367 cm-1; 1H
NMR (400 MHz, CDCl3): d = 8.35 (2H, d J = 7.2 Hz, Ar–H), 7.62 (1H, t
J = 7.6 Hz, Ar–H), 7.52 (2H, t, J = 7.2 Hz, J = 7.6 Hz, Ar–H), 7.38 (1H, d
J = 1.2 Hz CH-fouran) 4.48 (1H, d J = 3.2 Hz CH-fouran), 6.35 (1H, q,
J = 1.2 Hz CH-fouran), 5.20 (2H, s CH2 thiazol), 3.86 (2H, s CH2) ppm; 13C
NMR (75 MHz, CDCl3): 177.20 (C=O), 172.30 (C=O), 171.80 (N–C–S), 148.25
(C), 142.83 (CH), 135.04 (C), 133.12 (CH), 130 (2CH), 128.20 (2CH), 110.80 (CH),
109.85 (CH), 40 (CH2 thiazol), 32 (CH2) ppm; MS (EI, 70 eV) m/z (%): 300 (M?),
195, 105, 77, 51; Anal. calcd. for C15H12N2O3S; C: 59.99, H: 3.99, N: 9.33, S:
10.68, Found: C: 60.09, H: 3.95, N: 9.43, S: 10. 57.
(Z)-4-chloro-N-(3-(furan-2-ylmethyl)-4-oxothiazolidin-2-ylidene)benzamide
(5a)
Dark yellow solid; Yield = 89%, m.p. = 196–197 °C; IR (KBr): 3084 (C–H
aromatic), 2964 (C–H aliphatic), 1743 (C=O), 1640 (C=O thiazol), 1590, 1482,
1359 cm-1; 1H NMR (400 MHz, CDCl3): d = 8.28 (2H, d J = 8.4 Hz, Ar–H), 7.48
(2H, d J = 8.4 Hz, Ar–H), 7.38 (1H, d J = 1.2 Hz CH-fouran), 6.46 (1H, d
J = 3.2 Hz CH-fouran), 6.35 (1H, q J = 1.2 Hz CH-fouran), 5.20 (2H, s CH2
thiazol), 3.85 (1H, s CH2) ppm; 13C NMR (75 MHz, CDCl3): 176.40 (C=O), 172.50
(C=O), 172.20 (N–C–S), 148.30 (C), 142.80 (CH), 139.67 (C), 133.71 (C), 131.51
(2CH), 128.80 (2CH), 110.90 (CH), 110.95 (CH),40 (CH2 thiazol), 32 (CH2) ppm;
MS (EI, 70 eV) m/z (%): 334 (M?), 336 (M ? 2), 195, 141,139, 111, 81; Anal.
calcd. for C15H11ClN2O3S; C: 53.79, H: 3.28, N: 8.36, S: 9.58, Found: C: 53. 90, H,
3.35, N: 8. 29, S: 9.53.
(Z)-N-(3-(furan-2-ylmethyl)-4-oxothiazolidine-2-ylidene)-4-methylbenzamide (6a)
Light brown solid; Yield = 82%, m.p. = 196–197 °C, IR (KBr): 3116 (C–H
aromatic), 2926 (C–H aliphatic), 1736 (C=O), 1684 (C=O thiazol), 1605, 1497,
1568, 1516 cm-1; 1H NMR (400 MHz, CDCl3): d = 8.25 (2H, d J = 8.00 Hz, Ar–
H), 7.37 (1H, d), 7.31 (2H, d, J = 8.00 Hz, Ar–H), 6.46 (1H, d J = 3.2 Hz CH-
fouran), 6.34 (1H, q J = 3.2 Hz CH-fouran), 5.18 (2H, s CH2 thiazol), 3.84 (2H, s
CH2), 2.46 (3H, s CH3) ppm; 13C NMR (75 MHz, CDCl3): 177.17 (C=O), 172.56
(C=O), 171.17 (N–C–S), 148.57 (C), 144.14 (C), 142.58 (CH), 132.62 (C), 130.24
(2CH), 129.23 (2CH), 127.45 (CH), 110.57 (CH), 109.88 (CH), 109.12 (CH), 39.95
(CH2 thiazol), 33.03 (CH2), 21.83 (CH3). MS (EI, 70 eV) m/z (%): 314 (M?), 300,
195, 119,105, 91; Anal. calcd. for C16H14N2O3S; C: 61.14, H: 4.45, N: 8.91, S:
10.21, Found: C: 61.09, H: 4.47, N: 8.87, S: 10.17.
(Z)-N-(4-oxo-3-(pyridin-2-ylmethyl)thiazolidine-2-ylidene)benzamide (4b) Green
solid; Yield = 82%, m.p. = 216–218 °C; IR (KBr): 3080 (C–H aromatic), 2976,
123

M. Hossaini et al.
2933 (C–H aliphatic), 1733 (C=O), 1640 (C=O thiazol), 1595, 1484, 1374 cm-1; 1H
NMR (400 MHz, CDCl3): d = 8.59 (1H, d J = 4.4 CH-pyridine), 8.13 (2H, d
J = 7.6 Ar–H), 7.72 (1H, t J = 7.6, J = 8 Ar–H), 7.57 (1H, d J = 7.6 CH-
pyridine), 7.43 (2H, t J = 7.6, J = 7.6 Ar–H), 7.35 (1H d J = 8 CH-pyridine), 7.23
(1H t J = 5.2 CH-pyridine), 5.33 (2H, s CH2 thiazol), 3.48 (2H, s CH2) ppm; 13C
NMR (75 MHz, CDCl3): 177.21 (C=O), 172.99 (C=O), 172.02 (N–C–S), 154.49
(C), 149.96 (CH), 136.87 (CH), 135 (C), 133.11 (CH), 130.04 (2CH) 128.35 (2CH),
122.80 (CH), 121.50 (CH), 49 (CH2 thiazol), 32 (CH2) ppm; MS (EI, 70 eV) m/z
(%): 311 (M?), 206, 105,92, 77; Anal. calcd. for C16H13N3O2S; C: 61.69, H: 4.17,
N: 13.49, S: 10.30, Found: C: 61. 58, H: 4.20, N: 13.59, S: 10.21.
(Z)-4-chloro-N-(4-oxo-3-(pyridin-2-ylmethyl)thiazolidin-2-ylidene)benzamide (5b)
Green solid; Yield = 85%, m.p. = 225–226 °C, IR (KBr): 3082 (C–H aromatic),
2955 C–H aliphatic),, 1740 (C=O), 1641 (C=O thiazol), 1591, 1483, 1376 cm-1; 1H
NMR (400 MHz, CDCl3): d = 8.58 (1H, d J = 4.8 Hz CH-pyridine), 8.16 (2H, d
J = 8.4 Hz Ar–H), 7.70 (1H, t J = 7.6 Hz CH-pyridine), 7.39 (2H, d J = 8.4 Hz
Ar–H), 7.30 (1H, d CH-pyridine), 7.23 (1H, t J = 4.8 Hz CH -pyridine), 5.31 (2H, s
CH2 thiazol), 4.00 (2H, s CH2) ppm; 13C NMR (75 MHz, CDCl3): 176.26 (C=O),
172.91 (C=O), 172.53 (N–C–S), 154.4 (C), 149.96 (CH), 139.53 (C), 136.75 (C &
CH), 133.59 (CH), 131.42 (2CH), 128.64 (2CH), 48.49 (CH2), 33.22 (CH2) ppm;
MS (EI, 70 eV) m/z (%): 345 (M?), 347 (M ? 2), 271, 206, 139, 111, 92, 75. Anal.
calcd. for C16H12ClN3O2S; C: 55.59, H: 3.47, N: 12.15, S: 9.27, Found: C: 55. 49, 3.
49, N: 12.23, S: 9.17.
(Z)-4-methyl-N-(4-oxo-3-(pyridin-2-ylmethyl)thiazolidin-2-ylidene)benzamide (6b)
Green solid, Yield = 79%, m.p. = 224–225 °C, IR (KBr): 3098 (C–H aromatic),
2986 (C–H aliphatic), 1741 (C=O), 1637 (C=O thiazol), 1605, 1515, 1600,
,
1479 cm-1 1H NMR (400 MHz, CDCl3): d = 8.60 (1H, d J = 4.8 Hz CH-
pyridine), 8.03 (2H, d J = 8.4 Hz Ar–H), 7.70 (1H, t CH-pyridine), 7.32 (1H, d CH-
pyridine), 7.28 (1H, t), 7.21 (2H, d J = 8 Hz Ar–H), 5.33 (2H, S CH2 thiazol), 3.97
(2H, S CH2), 2.41 (3H, S CH3) ppm; 13C NMR (75 MHz, CDCl3): 177.15 (C=O),
173.02 (C=O), 171.45 (N–C–S), 154.57 (C), 194.54 (CH), 144.02 (C), 136.84 (CH),
132.47 (C), 130.15 (2CH), 129.09 (2CH), 122.67 (CH), 121.47 (CH), 48.40 (CH2),
33.21 (CH2), 21.78 (CH3) ppm; MS (EI, 70 eV) m/z (%): 325 (M?), 206, 119, 91.
Anal. calcd. for C17H15N3O2S; C: 62.76, H: 4.61, N: 12.92, S: 9.86, Found: C:
62.69, H: 4.60, N: 12.88, S: 9.78.
(Z)-N-(3-(5-chloro-2-phenoxyphenyl)-4-oxothiazolidin-2-ylidene)benzamide
(4c)
light yellow solid; Yield = 80%, m.p. = 167–168 °C; IR (KBr): 3042 (C–H
aromatic), 2965 (C–H aliphatic), 1740 (C=O), 1642 (C=O thiazol), 1590, 1577,
1
1485, 1356 cm-1; H NMR (400 MHz, CDCl3): d = 8.10 (2H, d J = 7.2 Hz Ar–
H), 7.57 (1H, t J = 7.2, J = 7.6 Hz Ar–H), 7.45-7.42 (3H, m), 7.26-6.98 (7H, m
CH phenoxyphenyl), 3.34 (2H, q, diastereotopic thiazol) ppm; 13C NMR (75 MHz,
CDCl3): 177.22 (C=O), 17.50 (C=O), 155.90 (N–C–S), 152.11 (C), 134.90 (C),
133.35 (C), 131.09 (CH), 130.13 (2CH), 130.06 (2CH), 129.95 (2CH), 128.43
(2CH), 128.10 (C), 126.18 (CH), 124.57 (CH), 122.11 (CH), 119.45 (2CH), 31.50
(CH2) ppm; MS (EI, 70 eV) m/z (%): 423 (M?), 425 (M ? 2), 405 329, 331, 105,
123

Novel (4-oxothiazolidine-2-ylidene)benzamide derivatives:…
77; Anal. calcd. for: C22H15ClN2O3: C: 62.50, H: 3.54, N: 6.62, S: 7.58, Found: C:
62.59, H: 3. 45, N: 6.73, S: 7.49.
(Z)-4-chloro-N-(3-(5-chloro-2-phenoxyphenyl)-4-oxothiazolidin-2-ylidene) benza-
mide (5c) yellow solid; Yield = 78%, m.p. = 210–211 °C; IR (KBr): 3094 (C–
H aromatic), 2978, 2934 (C–H aliphatic), 1736 (C=O), 1649 (C=O thiazol), 1587,
.
1571, 1479, and 1359 cm-1 1H NMR (400 MHz, CDCl3): d = 8.02 (2H, d
J = 8.4 Hz Ar–H), 7.46 (H, S), 7.43 (2H d J = 8.4 Hz Ar–H), 7.30-6.97 (7H, m
phenoxyphenyl), 3.90 (2H, q diastereotopic) ppm; 13C NMR (75 MHz, CDCl3):
176.33 (C=O), 172.15 (C=O), 171.41 (N–C–S), 155.71 (C), 152.11 (C), 139.92 (C),
133.42 (C), 131.49 (2CH), 131.16 (CH), 129.99 (2CH), 128.76 (2CH), 128 11
(2CH), 126.02 (CH). 124.64 (CH), 120.10 (CH), 119.41 (2CH), 32 (CH2) ppm; MS
(EI, 70 eV) m/z (%): 457 (M?), 459 (M ? 2), 461 (M ? 4), 363, 365, 367, 139,
111, 75; Anal. calcd. for: C22H14Cl2N2O3: C: 57. 79, H: 3.06, N: 6.12, S: 7.01,
Found: C: 58. 77, H: 3.13, N: 6.19, S: 6. 96.
(Z)-N-(3-(5-chloro-2-phenoxyphenyl)-4-oxothiazolidin-2-ylidene)-4-methylbenza-
mide (6c) Yellow crystal, Yield = 71%, m.p. = 160 °C, Yield = 80%, IR (KBr):
3060 (C–H aromatic), 2931 (C–H aliphatic), 1748 (C=O), 1685 (C=O thiazol),
1
1608, 1495, 1584, 1513 cm-1, H NMR (400 MHz, CDCl3): d = 7.98 (2H, d,
J = 8.2 Hz Ar–H), 7.46-7.41 (2H, m phenoxyphenyl), 7.24-7.29 (2H Ar–H), 7.25-
6.98 (7H, m phenoxyphenyl), 7.00 3.89 (2H, q diastereotopic J = 18 Hz), 2.43 (3H.
s CH3) ppm; 13C NMR (75 MHz, CDCl3): 177.22 (C=O), 171.55(C=O), 170.98 (N–
C–S), 155.78 (C), 152.17(C), 144.19(C), 132.33(C), 131.02 (CH), 130.23 (2CH),
130.09 (CH), 129.94 (2CH), 129.18 (2CH), 128.06 (CH), 126.20 (CH), 124.55
(CH), 120.08 (CH), 119.46 (2CH), 33.10 (CH2), 21.82 (CH3) ppm; MS (EI, 70 eV)
m/z (%): 437 (M?), 439 (M ? 2), 364, 347, 343, 119, 91; Anal. calcd. for:
C23H17ClN2O3: C: 63.15, H: 3.89, N: 6.40, S: 7.33. Found: C: 63.14, H: 3.86, N:
6.43, S: 7.29.
(Z)-N-(3-(naphthalene-2-yl)-4-oxothiazolidine-2-ylidene)benzamide (4d) Almond
green solid; Yield = 80%, m.p. = 170–171 °C, IR (KBr): 3057 (C–H aromatic),
2971 (C–H aliphatic), 1748 (C=O), 1643 (C=O thiazol), 1598, 1511, 1483,
,
1347 cm-1 1H NMR (400 MHz, CDCl3): d = 8.08 (1H, d J = 8.4 Hz, naph-
thalene), 8.02 (1H, d J = 8.8 Hz, naphthalene), 7.78 (2H, d J = 7.2 Hz ArH), 7.68
(1H, t J = 7.2 Hz Ar–H), 7.58-7.24 (7H, m), 4.16 (2H, q diastereotopic
J = 18.4 Hz) ppm; 13C NMR (75 MHz, CDCl3): 177.50 (C=O), 172.50 (C=O),
171.98 (N–C–S), 134.80 (C), 134.44 (C), 133.15 (CH), 131.60 (C), 130.32 (CH),
130.03 (2CH), 129.30 (CH), 128.22 (2CH), 127.47 (C), 126.60 (CH), 126.70 (CH),
125.55 (CH), 122.95 (CH), 30.35 (CH2) ppm, MS (EI, 70 eV) m/z (%): 346 (M?),
241, 105, 77. Anal. calcd. for: C20H14N2O2S: C: 69.37, H: 4.04, N: 8.08, S: 9.25,
Found: C: 69.45, H: 4.10, N: 8.02, S: 9.31.
(Z)-N-4-chloro-N-(3-(naphthalene-2-yl)-4-oxothiazolidine-2-ylidene)benzamide (5d)
Green solid; Yield = 83%, m.p. = 155–156 °C, IR (KBr): 3055 (C–H aromatic),
2971 (C–H aliphatic), 1742 (C=O), 1644 (C=O thiazol), 1599, 1521, 1488 cm-1, 1H
NMR (400 MHz, CDCl3): d = 8.08 (1H, d J = 8.4 Hz naphthalene) 8.03 (1H, d
123

M. Hossaini et al.
J = 7.6 Hz naphthalene), 7.68 (2H, d J = 8.4 Hz Ar–H), 7.61-7.48 (5H, m
naphthalene), 7.25 (2H, d J = 8.4 Hz Ar–H), 4.18 (2H, q diastereotopic
J = 18.4 Hz) ppm; 13C NMR (75 MHz, CDCl3): 176.49 (C=O), 172.54 (C=O),
172.44 (N–C–S), 139.51 (C), 134.43(C), 133.32 (C), 131.48 (C), 131.38
(2CH),130.39 (CH), 129.19 (CH), 128.78 (CH), 128.53 (2CH), 127.49 (CH),
126.73 (C), 126.52 (CH), 125.50 (CH), 121.89 (CH), 33.46 (CH2) ppm; MS (EI,
70 eV) m/z (%): 380 (M?), 382 (M ? 2), 241, 139, 111. Anal. calcd. for:
C20H13ClN2O2S: C: 63.15, H: 3.42, N: 7.3, S: 8.43, Found: C: 63.18, H: 3.41, N:
7.29, S: 8.42.
(Z)-4-methyl-N-(3-(naphthalen-1-yl)-4-oxothiazolidin-2-ylidene) benzamide (6d)
Light gray; Yield = 77%, m.p. = 174–175 °C, IR (KBr): 3057 (C–H aromatic),
2978 (C–H aliphatic), 1729 (C=O), 1635 (C=O thiazol), 1516, 1608, and
.
1494 cm-1 1H NMR (400 MHz, CDCl3): d = 8.08 (1H, d, J = 8.4 Hz naph-
thalene), 8.02 (1H, d, J = 8.0 Hz naphthalene), 7.67 (2H, d J = 8 Ar–H) 7.64-7.49
(1H, m naphthalene), 7.05 (2H d J = 8 Ar–H) 4.20 (2H, q diastereotopic
J = 18.4 Hz), 2.32 (3H, S CH3) ppm; 13C NMR (75 MHz, CDCl3): 177.40 (C=O),
172.57 (C=O), 171.35 (N–C–S), 143.98 (C), 134.43 (C), 132.23 (C), 131.64 (C),
130.26 (C), 130.12 (2CH), 129.28 (CH), 128.96 (2CH), 128.71 (2CH), 127.42 (CH),
126.66 (CH), 126.57 (CH), 125.48 (CH), 122.00 (CH), 33.45 (CH2), 21.70 (CH3)
ppm; MS (EI, 70 eV) m/z (%): 360 (M?), 240, 119, 91; Anal. calcd. for:
C12H16N2O2S, C: 70, H: 4.4, N: 7.7, S: 8.9. Found: C: 72.10, H: 4.38, N: 7.69, S:
8.91.
X-ray crystal structure determination of compounds 4a and 4c
The crystallographic data for both complexes were collected at room temperature
on a Bruker Smart Apex II single-crystal diffractometer working with monochro-
matic Mo-Ka radiation and equipped with an area detector [26]. The structures
were solved by direct methods and refined against F2 with SHELXL-2014/7 [27]
with anisotropic thermal parameters for all non-hydrogen atoms. Idealized
geometries were assigned to the hydrogen atoms. Details for the X-ray data
collection are reported in Table 1. Complete crystallographic data have been
deposited with the Cambridge Crystallographic Data Centre as a supplementary
publication [28].
Results and discussion
Chemistry
In this article, a one-pot, multicomponent synthesis of thiazole derivatives bearing
an amide moiety have been performed by using benzoyl isothiocyanate derivatives
(1), the suitable heterocyclic (aromatic) amines (2) and methyl bromoacetate (3) in
the presence of triethylamine as a catalyst and bromine scavenger in acetonitrile as a
solvent. A proposed mechanism for the reaction is outlined in Scheme 1.
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Novel (4-oxothiazolidine-2-ylidene)benzamide derivatives:…
Table 1 Details for the X-ray data collection for compounds 4a and 4c
Compound
4a
4c
Formula
C15 H12 N2 O3
300.33
S
C22 H15 Cl N2 O3
422.87
S
Molecular weight
Crystal system
Space group
Triclinic
P-1
Triclinic
P-1
˚
a/A
8.468 (4)
8.993 (4)
9.768 (5)
83.209 (7)
73.129 (7)
70.881 (7)
672.4 (6)
2
10.577(7)
10.759(7)
11.262 (7)
62.670 (9)
63.120 (10)
81.479 (10)
1012.8 (11)
2
˚
b/A
˚
c/A
a/°
b/°
c/°
3
˚
Volume, A
Z
D
calc/g cm-3
1.483
1.387
F (000)
312
436
l(Mo-Ka)/mm-1
Reflections collected
Unique reflections
Observed reflections [I [ 2r(I)]
R, wR [I [ 2r(I)]
R, wR [all data]
0.252
0.318
10,967
10,975
4118
3614
3034;[Rint = 0.0341]
2855; [Rint = 0.0397]
R = 0.0434; wR = 0.1119
R = 0.0616; wR = 0.1237
R = 0.0468; wR = 0.1232
R = 0.0587; wR = 0.1338
h
h
i
h
ii
1=2
P
P
P
P
2
2
R ¼ jFo ÀFcj= jFoj; wR ¼
wðFo2ÀFc2Þ
=
wðFo2Þ
O
S
O
R
O
S
OMe
3
CH3CN
Reflux
N
H
C
N
H
N
R
NH2
2
Br
X
X
1
O
O
S
O
S
OMe
Et3N
O
N
R
N
N
NH
R
-MeOH
X
X
Scheme 1 Proposed mechanism for the formation of (4-oxothiazolidine-2-ylidene)benzamide
derivatives
123

M. Hossaini et al.
(4-Oxothiazolidine-2-ylidene) benzamide derivatives are synthesized via one-pot,
two-step cyclocondensation reaction. In the first step, benzoyl isothiocyanate (1)
reacts with heterocyclic aliphatic or aromatic amines (2) to produce N-(carbamoth-
ioyl) benzamide as an unsymmetrical thiourea. In the next step, methyl bromoac-
etate (3) is attacked by nucleophiles.
First, the reactions were investigated at room temperature for 8–10 h, but no
suitable progress of the reaction was observed. In order to improve the reaction
efficiency, the reaction was carried out under reflux conditions. The compounds
1
were characterized by IR, H NMR, 13C NMR spectra, mass spectrometry and
CHNS elemental analysis. In the case of compounds 4a and 4c, single crystals
adapted for X-ray diffraction analysis were obtained.
First, (Z)-4-chloro-N-(3-(furan-2-ylmethyl)-4-oxothiazolidine-2-ylidene) benza-
mide (5a) was synthesized and characterized. In the IR spectrum, C–H aliphatic and
aromatic bands were observed at 3084 and 2964 cm-1, and strong absorptions at
1743 and 1640 cm-1 were due to carbonyl groups. The 1H NMR spectrum showed
the presence of 2 aliphatic protons at 5.20 ppm (Cfuran ring–CH2–N), 3.85 ppm (CH2
thiazole), while aromatic protons of phenyl and furan rings appear at 8.28–6.35 ppm.
The 13CNMR spectrum of this compound showed carbonyl groups and carbon of the
thiazole ring at 176.40, 172.50 and 172.20 ppm, respectively. The mass spectrom-
etry and CHNS elemental analysis confirmed the proposed formula.
Various amines, such as substituted 2-furanmethylamine (a) 2-(aminomethyl)
pyridine (b), 5-chloro-2-phenoxyaniline (c), and 1-naphthylamine (d) were used to
1
give thiazolidinone derivatives (Scheme 2). Interestingly, in the HNMR spectra,
AB quartet systems were observed when aromatic compounds (1-naphthylamine
and 5-chloro-2-phenoxyaniline) were used. Aliphatic hydrogens in the thiazole ring
are diastereotopic, and they have different chemical shifts in the 1HNMR spectrum.
When the hydrogens are diastereotopic, they frequently split from each other, but in
O
O
S
O
S
C
CH3CN
Reflux, 4-6h
Et3N,
N
Br
N
R
NH2
+
H3CO
+
N
R
O
X
X
(1)
(2)
(3)
(4a-d)
(5a-d)
(6a-d)
X= H(4)
X= Cl (5)
X=CH3 (6)
O
R =
O
Cl
N
(c)
(d)
O
(a)
(b)
O
O
S
O
S
S
S
N
N
N
N
N
N
O
N
O
O
O
N
O
X
X
X
X
N
O
Cl
(4d-6d)
(4c-6c)
(4a-6a)
(4b-6b)
Scheme 2 Synthesis of (4-oxothiazolidine-2-ylidene)benzamide derivatives
123

Novel (4-oxothiazolidine-2-ylidene)benzamide derivatives:…
the case of aliphatic amines [2-furanmethylamine, 2-(aminomethyl) pyridine], the
rotation around the C—N bond inhibits the observation of the AB quartet system.
Crystal structure analysis for compounds 4a, 4c
The molecular structures of compounds 4a and 4c were established by single crystal
X-ray diffraction methods. The molecular structures of the compounds are reported
in Figs. 1 and 2 together with the atomic labeling scheme.
A list of the most important bond distances and angles are reported in the
figure captions. In both structures, the thiazolidinone group, the amide system, and
the aromatic rings are almost coplanar with a dihedral angle between the aromatic
rings and the mean plane of the thiazolidinone group of 6.54(2)° and 10.63(2)° for
4a and 4c, respectively. On the other hand, the furfuryl and the 1-chloro-4-
phenoxybenzene moieties in 4a and 4c, respectively, tend to dispose in order to
minimize the steric hindrance with the planar system. In particular, in 4a the mean
plane defined by the furfuryl group forms a dihedral angle of 71.65(2)° with the
planar system, while in 4c the mean plane defined by the chlorophenyl moiety forms
a dihedral angle of 76.64(2)° with the analogous planar system. This fact prevents
stacking molecules assisted by pi–pi interactions as observed in other similar
structures found in the Crystallographic Data Base [24, 25]. Nevertheless, hydrogen
bonds and Van der Waals interactions are present between adjacent molecules in the
crystal packing of both structures. In particular, the oxygen atoms of the
thiazolidinone and of the amide groups are involved in interactions with hydrogen
Fig. 1 Ortep view of molecular structure of compound 4a. Ellipsoids are drawn at their 30% probability
˚
level. Selected bond distances (A) and angles (deg): C1-C2 1.498(2), C1-S 1.8019(17), C2-O2
1.2010(18), C2-N1 1.3867(18), C3-N2 1.2855(17), C3-N1 1.3736(17), C3-S 1.7405(14), C4-O1
1.2228(17), C4-N2 1.3890(18), C4-C5 1.487(2), C11-N1 1.4666(18), C2-C1-S 108.40(10), O2-C2-N1
123.03(15), O2-C2-C1 126.28(14), N1-C2-C1 110.69(12), N2-C3-N1 119.02(12), N2-C3-S 128.98(11),
N1-C3-S 112.01(10), O1-C4-N2 123.85(13), O1-C4-C5 122.07(13), N2-C4-C5 114.08(12), C3-N1-C2
116.97(12), C3-N1-C11 121.37(11), C2-N1-C11 121.65(12), C3-N2-C4 118.34(12), C3-S-C1 91.85(7)
123

M. Hossaini et al.
Fig. 2 Ortep view of molecular structure of compound 4c. Ellipsoids are drawn at their 30% probability
˚
level. Selected bond distances (A) and angles (deg): C1-C2 1.498(3), C1-S 1.804(2), C2-O2 1.208(3), C2-
N1 1.389(3), C3-N2 1.289(2), C3-N1 1.384(3), C3-S 1.743(2), C4-O1 1.222(2), C4-N2 1.385(3), C4-C5
1.489(3), C22-N1 1.438(2), C2-C1-S 108.62(14), O2-C2-N1 123.7(2), O2-C2-C1 125.59(18), N1-C2-C1
110.75(18), N2-C3-N1 118.67(17), N2-C3-S 129.41(15), N1-C3-S 111.92(13), O1-C4-N2 124.65(18),
O1-C4-C5 121.74(18), N2-C4-C5 113.61(17), C3-N1-C2 116.80(17), C3-N1-C22 121.09(15), C2-N1-
C22 121.52(16), C3-N2-C4 118.00(17), C17-O3-C11 117.30(15), C3-S-C1 91.91(9)
atoms of the aromatic rings of adjacent molecules with O_C (H) distances ranging
˚
from 3.335(2) to 3.590(3) A.
Conclusions
In summary, we have introduced a novel and efficient method for the synthesis of
new derivatives of (4-oxothiazolidine-2-ylidene)benzamide via a one-pot reaction
between benzoyl isothiocyanate, various amines and methyl bromoacetate. The
single crystal X-ray diffraction analysis unequivocally reveals the exact identity of
the compounds. The procedure is extremely useful in synthetic and medicinal
chemistry as it provides the desired products in a one-pot process in excellent to
good yield.
Acknowledgements We gratefully acknowledge financial support from the Research Council of the
University of Sistan and Baluchestan. Also, we wish to express our gratitude to Dr. Majid. Kolahdoozan
for his helpful discussions.
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