Synthesis and structure of new 5-(arylidene)-3-(4-methylbenzoyl) thiazolidine-2,4-diones

Article abstract of DOI:10.1002/jhet.288

(Chemical Equation Presented) The derivatives of 5-substituted-2,4- thiazolidinedione have a broad spectrum of biological activities. In this article, new 5-(arylidene)-3-(4-methylbenzoyl)thiayolidine-2,4-diones 3a-k, with arylidene groups such as 4-pheny

Full text of DOI:10.1002/jhet.288

224
Synthesis and Structure of New 5-(Arylidene)-3-
(4-methylbenzoyl)thiazolidine-2,4-diones
Vol 47
a
Katarina M. Popov-Pergal, * Dejan Poleti, Milica P. Rancic, Antun Meden,
b
a
c
ˇ ´
and Marija V. Pergald
aChemistry Department, Faculty of Forestry Science, University of Belgrade, Belgrade 11000,
Serbia
bDepartment of General and Inorganic Chemistry, Faculty of Technology and Metallurgy,
University of Belgrade, Belgrade 11000, Serbia
cFaculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana SI-1000,
Slovenia
dPolymer Department, Center for Chemistry, Institute of Chemistry, Technology and Metallurgy,
Belgrade 11000, Serbia
*E-mail: pergal@eunet.rs.
Received June 16, 2009 accepted 11 October 2009
DOI 10.1002/jhet.288
Published online 5 January 2010 in Wiley InterScience (www.interscience.wiley.com).
The derivatives of 5-substituted-2,4-thiazolidinedione have a broad spectrum of biological activities.
In this article, new 5-(arylidene)-3-(4-methylbenzoyl)thiayolidine-2,4-diones 3a–k, with arylidene
groups such as 4-phenylbenzylidene 3a, 3,4-dimethoxybenzylidene 3b, 2-hydroxybenzylidene 3c, 4-
ethoxybenzylidene 3d, 5-methyl-2-furfurylidene 3e, 4-dimethylaminobenzylidene 3f, 1-naphthylidene
3g, 3,4-methylenedioxybenzylidene 3h, 4-benzyloxybenzylidene 3i, benzylidene 3j, and 4-methoxyben-
zylidene 3k, were synthesized by direct acylation of alkali metal salts of 5-arylidene-2,4-thiazolidine-
diones with 4-methylbenzoylchloride. Their structures were confirmed by elemental analysis, IR, 1H
NMR and MS spectroscopy. In addition, crystal structure of the compound 3d was determined using
single-crystal X-ray diffraction data.
J. Heterocyclic Chem., 47, 224 (2010).
INTRODUCTION
compound 3d was also determined using single-crystal
X-ray diffraction data.
Thiazolidinone derivates are reported to show variety
of biological activities. Depending on the substituents,
especially thiazolidinediones can produce different phar-
macological activities such as antibacterial, antifungal
[1], anticonvulsant [2], antidiabetic [3], cyclooxygenase
and lipogenase inhibitory [4], antioxidant [5], and anti-
proliferative [6] activity. Moreover, the importance of 5-
substituted-2,4-thiazolidinedione and their derivatives is
due to their biological activities including antimicrobial
[1] and fungicidal activity [7], as well as their utilization
in a variety of therapeutic areas [8–14].
RESULTS AND DISCUSSION
The reactive methylene group of the 2,4-thiazolidine-
dione has previously been successfully condensed with
aldehydes, forming respectively 5-arylidene-2,4-thiazoli-
dinediones 1a–k [18]. These compounds were later trans-
formed in their potassium salts 2a–k [19]. By direct acy-
lation of solid alkali metal salts of 5-arylidene-2,4-thiazo-
lidinediones with 4-methylbenzoylchloride in refluxing
dry acetone the corresponding 5-(arylidene)-3-(4-methyl-
benzoyl)thiazolidine-2,4-diones 3a–k were prepared. The
obtained compounds 3a–k were synthesized as yellow
crystals in high yields (56.2–99.4%). The synthesis route
is shown in Scheme 1.
In some heterocyclylbenzenes [15,16] and substituted
pyrazoles [17], which have herbicidal and defoliant
characteristic, there is a 3-methylbenzoyl substructure.
This study is focused on the link of 5-arylidene-2,4-thia-
zolidinediones and bioactive structural unit, 3-methyl-
benzoyl group, in order to find novel potential herbi-
cides and defoliants. Crystal structure of the selected
All the newly synthesized compounds were character-
1
ized by elemental analysis, IR, H NMR, and MS (see
C
V
2010 HeteroCorporation

January 2010
Synthesis and Structure of New 5-(Arylidene)-3-
(4-methylbenzoyl)thiazolidine-2,4-diones
225
Scheme 1
The characteristic feature in crystal packing is the stack-
ing of molecules in columns running along b-axis (Fig. 2).
These columns further make a regular grid parallel to the
planes (1 0 1) and (1 0 0) [Fig. 2(a)]. Within the columns
there are stacking pꢁp interactions, which alternatively
involve two benzylidene rings or pairs of both benzylidene
and thiazolidine-2,4-dione rings [Fig. 2(b)]. As, for exam-
ple, distances between planes of two benzylidene rings are
˚
only 3.32 and 3.33 A the stacking p–p interactions can be
described as very strong. In addition to van der Waals con-
tacts, between the neighboring columns there are several
CAHꢃꢃꢃO interactions involving mainly C atoms from ter-
minal CH3 groups, as well as few C atoms from 4-methyl-
benzoyl and benzylidene rings. In this way, the columns
are only loosely connected to each other.
‘‘Experimental’’ section). The elemental analysis and
MS of 5-(arylidene)-3-(4-methylbenzoyl)thiazolidine-
2,4-diones 3a–k, agreed with the molecular formula of
these compounds. The structure of synthesized com-
On the basis of presented crystal structure of 3d
compound it can be assumed that: (a) in all compounds
(3a–k) the main part of molecule, including benzylidene
and thiazolidine-2,4-dione rings, is almost planar; (b) p–
p interactions between aromatic rings have a predomi-
nant role in molecular packing; (c) in all derivatives the
C11AC12 bond is longer than double (C¼¼C) bond,
while the C12AC13 bond is shorter than the expected
value for a single bond, probably because of delocaliza-
tion of p-electrons through the whole substructure
(C11¼¼CHACarom). This delocalization is a reason why
the attempts to carry out some addition reactions, which
are inherent for the double bond, were unsuccessful.
1
pounds was confirmed by H NMR and IR spectroscopy.
1H NMR spectra 5-(arylidene)-3-(4-methylbenzoyl)thia-
zolidine-2,4-diones 3a–k, clearly showed presence of
benzoyl protons (d ꢀ 7.3 and 7.8 ppm) and methyl pro-
tons (d ꢀ 2.45 ppm) in comparison with spectra of 5-
arylidene-2,4-thiazolidinediones 1a–k [18]. IR spectra of
all newly synthesized compounds 3a–k, contain charac-
teristic bands attributed to the methyl-benzoyl (C¼¼O,
about 1760 cmꢁ1) and benzoyl (about 1450 and 1600
cmꢁ1) vibrations that are used in the structural charac-
terization of this type of compounds.
Crystal structure of the compound 3d. The molecu-
lar structure of compound 3d is shown in Figure 1, and
selected bond lengths and bond angles are listed in Ta-
ble 1. Bond lengths and angles are in well agreement
with some parent and similar compounds [20–22]. The
main part of molecule, including the side ethoxy group,
is almost planar with dihedral angle between benzyli-
dene and thiazolidine-2,4-dione rings of only 5.8ꢂ. This
is as expected, since practically the same angles (5.4ꢂ–
5.9ꢂ) are found in some similar compounds [20,21]. The
slight deviation from planarity can be attributed to the
short repulsive SꢃꢃꢃH14–C14 contact with SꢃꢃꢃC14 dis-
EXPERIMENTAL
Materials and methods. The solvent and all reagents used
in this study were purchased from commercial suppliers and
were used as received. The melting points were obtained with
Table 1
ꢂ
˚
Selected bond lengths (A) and bond angles ( ) for 3d.
˚
Bond lenghts (A)
SAC11
SAC10
O1AC16
O1AC19
O2AC10
O3AC9
O4AC8
1.7586(16)
1.7620(18)
1.360(2)
1.450(2)
1.210(2)
1.206(2)
1.200(2)
1.397(2)
NAC9
NAC8
C1AC7
1.414(2)
1.459(2)
1.502(3)
1.471(2)
1.480(2)
1.342(2)
1.450(2)
1.501(3)
C4AC8
C9AC11
C11AC12
C12AC13
C19AC20
˚
tance of only 3.260(2) A. On the other hand, dihedral
angle between planes of thiazolidine-2,4-dione and
methylbenzylidene rings is 67.1ꢂ.
NAC10
Bond angles (ꢂ)
C11ASAC10
C16AO1AC19
C10ANAC9
C10ANAC8
C9ANAC8
O4AC8AN
O4AC8AC4
NAC8AC4
O3AC9AN
O3AC9AC11
NAC9AC11
92.30(18)
117.49(13)
116.01(14)
121.01(14)
122.44(13)
118.55(16)
124.94(16)
116.50(15)
123.22(16)
126.70(16)
110.04(14)
O2AC10AN
O2AC10AS
NAC10AS
C12AC11AC9
C12AC11AS
C9AC11AS
C11AC12AC13
O1AC16AC15
O1AC16AC17
O1AC19AC20
125.19(16)
123.99(14)
110.78(12)
120.63(15)
128.61(14)
110.75(12)
131.73(16)
124.91(15)
115.92(15)
107.02(16)
Figure 1. The molecular structure of compound 3d.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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K. M. Popov-Pergal, D. Poleti, M. P. Rancic, A. Meden, and M. V. Pergal
226
Vol 47
Figure 2. The packing of molecules 3d (heteroatoms are dark, hydrogen atoms are omitted for clarity): (a) projection onto ac-plane and (b) projec-
tion approximately parallel to the (101) plane.
STUART SMP 10 melting point apparatus. Infrared spectra (m
in cmꢁ1) were recorded on a Perkin Elmer FTIR 1725 X spec-
Table 2
trophotometer using KBr disks. The 1H NMR spectra were
recorded on a Varian Gemini 200 (200 MHz) instrument;
Crystal data and refinement details for 3d.
Empirical formula
Formula weight
C20H17NO4S
367.41
chemical shifts (d) are given relative to tetramethylsilane
(TMS). The mass spectra were obtained on Finnigan MAT–
8230 BE spectrometer with EI–CI source at 200ꢂC, EI: 70 eV,
0.5 mA; CI: 1 m Torr of isobutane, 150 eV, 0.2 mA.
Crystal system
Space group
monoclinic
P21/n
14.4880(5)
6.9780(3)
˚
a (A)
˚
Single-crystals of the compound 3d were obtained by
recrystallization from EtOH. X-ray diffraction data were col-
lected at 150 K on a Nonius Kappa CCD diffractometer using
Mo Ka radiation. The structure was solved by direct methods
and refined by a full-matrix least-squares procedure based on
F2 using the programs from WinGX suite [23]. All nonhydro-
gen atoms were refined anisotropically, while the hydrogen
atoms were found in DF maps and were refined isotropically
with no constraints. Selected crystal data and refinement
results are listed in Table 2.
Syntheses. General procedure for the preparation of the
5-(arylidene)-3-(4-methylbenzoyl)thiazolidine-2,4-diones 3a–
k. 5-Arylidene-2,4-thiazolidinedione potassium salts (1 mmol)
were suspended in dry acetone (20 mL) and 4-methylbenzoyl-
chloride (1 mmol) was added at room temperature. The reac-
tion mixtures were stirred at 60ꢂC for 2 h and cooled to room
temperature. Finally, the reaction mixtures were filtered and
acetone was removed to give the crystalline products. The
products were recrystallized from absolute EtOH.
b (A)
˚
c (A)
18.0600(7)
90
110.7290(10)
90
1707.62(12)
4
1.429
a (ꢂ)
b (ꢂ)
c (ꢂ)
3
˚
V (A )
Z
Calculated density (g cmꢁ3
)
Absorption coefficient (mmꢁ1
F(000)
)
0.216 mm
768
Crystal size (mm)
H range (ꢂ)
Limiting indices
0.75 ꢄ 0.70 ꢄ 0.05
3.16–26.37
ꢁ17 ꢅ h ꢅ 18,
ꢁ8 ꢅ k ꢅ 8,
ꢁ22 ꢅ l ꢅ 22
6383/3453 (Rint ¼ 0.0313)
3453/0/304
1.030
Reflections collected/unique
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2r(I)]
R indices (all data)
R1 ¼ 0.0378, wR2 ¼ 0.0786
R1 ¼ 0.0592, wR2 ¼ 0.0874
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DOI 10.1002/jhet

January 2010
Synthesis and Structure of New 5-(Arylidene)-3-
(4-methylbenzoyl)thiazolidine-2,4-diones
227
1
1296, 1197, 884, 769, 659; H NMR (CDCl3), d, ppm (J, Hz):
2.45 (s, 3H, CH3), 3.09 (s, 6H, N (CH3)2), 6.75 (2Harom, m
AA0 J1 ¼ 7.0, J2 ¼ 1.99), 7.33 (2Harom, m AA0 J1 ¼ 7.99, J2 ¼
5-(4-Phenylbenzylidene)-3-(4-methylbenzoyl)thiazolidine-2,4-
dione (3a). This compound was obtained as yellow crystals
(ethanol), yield 69.3%, mp 183ꢂC; IR, m, cmꢁ1
: 3035
0.4), 7.44 (2Harom, m BB0 J1 ¼ 7.2, J2 ¼ 1.99), 7.83 (2Harom
,
(¼¼CAH), 2925, 2794 (CAH), 1762 (C¼¼O), 1716 (C¼¼O),
m BB0 J1 ¼ 8.4, J2 ¼ 1.99), 7.85 (s, 1H, ¼¼CH); m/z (CIMS):
366 (Mþ). Anal. Calcd. for C20H18N2O3S (366.4): C, 65.49;
H, 4.95; N, 7.64; S, 8.75. Found: C, 65.29; H, 4.83; N, 7.59;
S, 8.83.
1693 (C¼¼O), 1603, 1515, 1448 (C¼¼C), 1408 (CAN), 1258,
1
1177, 1063, 837, 718, 691; H NMR (CDCl3), d, ppm (J, Hz):
2.46 (s, 3H, CH3), 7.34 (d, 2Harom, J ¼ 8.0), 7.41–7.73 (m,
9Harom), 7. 87 (d, 2Harom, J ¼ 8.4), 7.99 (s, 1H, ¼¼CH); m/z
(CIMS): 398 (Mþ). Anal. Calcd. for C24H17NO3S (399.5): C,
72.16; H, 4.29; N, 3.51; S, 8.03. Found: C, 72.01; H, 4.21; N,
3.59; S, 8.05.
5-(1-Naphthylidene)-3-(4-methylbenzoyl)thiazolidine-2,4-dione
(3g). This compound was obtained as yellow crystals (ethanol),
yield 99.4%, mp 147ꢂC; IR, m, cmꢁ1: 3046 (¼¼CAH), 2909
(CAH), 1762 (C¼¼O), 1717 (C¼¼O), 1690 (C¼¼O), 1603, 1572,
1448 (C¼¼C), 1397 (CAN), 1298, 1181, 891, 736, 641; 1H NMR
(CDCl3), d, ppm (J, Hz): 2.47 (s, 3H, CH3), 7.33 (d, 2Harom, J ¼
8.2), 7.55–8.15 (m, 9Harom), 8.69 (s, 1H, ¼¼CH); m/z (CIMS): 373
(Mþ). Anal. Calcd. for C22H15NO3S (373.4): C, 70.76; H, 4.05;
N, 3.75; S, 8.59. Found: C, 70.57; H, 4.02; N, 3.77; S, 8.66.
5-(3,4-Methylenedioxybenzylidene)-3-(4-methylbenzoul)th-
iazolidine-2,4-dione (3h). This compound was obtained as
yellow crystals (ethanol), yield 71.2%, mp 152ꢂC; IR, m,
cmꢁ1: 3051 (¼¼CAH), 2997, 2908 (CAH), 1752 (C¼¼O), 1713
(C¼¼O), 1689 (C¼¼O), 1607, 1590, 1449 (C¼¼C), 1365 (CAN),
5-(3,4-Dimethoxybenzylidene)-3-(4-methylbenzoyl)thiazoli-
dine-2,4-dione (3b). This compound was obtained as yellow
crystals (ethanol), yield 56.2%, mp 228ꢂC; IR, m, cmꢁ1: 3007
(¼¼CAH), 2960, 2838 (CAH), 1751 (C¼¼O), 1712 (C¼¼O),
1686 (C¼¼O), 1591, 1512, 1447 (C¼¼C), 1418 (CAN), 1272,
1
1242, 1180, 1074 (CAO), 857, 730, 678; H NMR (CDCl3), d,
ppm (J, Hz): 2.45 (s, 3H, CH3), 3.95 (s, 6H, 2 CH3), 6.96–
7.20 (m, 3Harom), 7.31 (d, 2Harom, J ¼ 8.0), 7.83 (d, 2Harom, J
¼ 8.4), 7.89 (s, 1H, ¼¼CH); m/z (CIMS): 383 (Mþ). Anal.
Calcd. for C20H17NO5S (383.2): C, 62.66; H, 4.74; N, 3.65; S,
8.37. Found: C, 62.50; H, 4.71; N, 3.68; S, 8.57.
1
1263, 1066 (CAO), 862, 726, 658; H NMR (CDCl3), d, ppm
5-(2-Hydroxybenzylidene)-3-(4-methylbenzoyl)thiazolidine-
2,4-dione (3c). This compound was obtained as yellow crystals
(ethanol), yield 83.4%, mp 233ꢂC; IR, m, cmꢁ1: 3415 (OAH),
3043 (¼¼CAH), 2764 (CAH), 1745 (C¼¼O), 1701 (C¼¼O), 1681
(C¼¼O), 1602, 1510, 1455 (C¼¼C), 1412 (CAN), 1293, 1265,
(J, Hz): 2.46 (s, 3H, CH3), 6.09 (s 2H, AOCH2OA), 7.33 (d,
2Harom, J ¼ 8.2), 6.92–7.12 (m, 3Harom), 7.81 (d, 2Harom, J ¼
7.8), 8.85 (s, 1H, ¼¼CH); m/z (CIMS): 367 (Mþ). Anal. Calcd.
for C19H13NO5S (367.4): C, 62.12; H, 3.57; N, 3.81; S, 8.73.
Found: C, 61.94; H, 3.50; N, 3.77; S, 8.80.
1
1152 (CAO), 838, 750, 684; H NMR (CDCl3), d, ppm (J, Hz):
5-(4-Benzyloxybenzylidene)-3-(4-methylbenzoyl)thiazolidine-
2,4-dione (3i). This compound was obtained as yellow crystals
2.47 (s, 3H, CH3), 7.33–7.61 (m, 4Harom), 7.80 (d, 2 Harom, J ¼
8.2), 7.99 (s, 1H, ¼¼CH), 8.11 (d, 2 Harom, J ¼ 8.0); m/z (CIMS):
339 (Mþ). Anal. Calcd. for C18H13NO4S (339.4): C, 63.77; H,
3.86; N, 4.13; S, 9.46. Found: C, 63.47; H, 3.76; N, 3.83; S, 9.55.
5-(4-Ethoxybenzylidene)-3-(4-methylbenzoyl)thiazolidine-
2,4-dione (3d). This compound was obtained as yellow crys-
tals (ethanol), yield 97.4%, mp 178ꢂC; IR, m, cmꢁ1: 3041
(¼¼CAH), 2936, 2883 (CAH), 1755 (C¼¼O), 1716 (C¼¼O),
1690 (C¼¼O), 1596, 1509, 1448 (C¼¼C), 1398 (CAN), 1281,
(ethanol), yield 96.3%, mp 144ꢂC; IR, m, cmꢁ1
: 3034
(¼¼CAH), 2923, 2882 (CAH), 1763 (C¼¼O), 1716 (C¼¼O),
1687 (C¼¼O), 1593, 1511, 1453 (C¼¼C), 1386 (CAN), 1292,
1149 (CAO), 831, 783, 698; 1H NMR (CDCl3), d, ppm (J,
Hz): 2.45 (s, 3H, CH3), 5.15 (s, 2H, CH2O), 7.07–7.53 (m,
11Harom), 7.82 (2Harom, m BB0 J1 ¼ 6.6, J2 ¼ 1.6), 7.89 (s,
1H, ¼¼CH); m/z (CIMS): 429 (Mþ). Anal. Calcd. for
C25H19NO4S (429.5): C, 69.91; H, 4.46; N, 3.26; S, 7.47.
Found: C, 69.74; H, 4.37; N, 3.23; S, 7.52.
5-Benzylidene-3-(4-methylbenzoyl)thiazolidine-2,4-dione
(3j). This compound was obtained as yellow crystals (ethanol),
yield 86.3%, mp 118ꢂC; IR, m, cmꢁ1: 3056 (¼¼CAH), 2917
(CAH), 1758 (C¼¼O), 1717 (C¼¼O), 1692 (C¼¼O), 1606, 1492
(C¼¼C), 1373 (CAN), 1254, 1182, 883, 686; 1H NMR
(CDCl3), d, ppm (J, Hz): 2.46 (s, 3H, CH3), 7.33 (d, 2Harom, J
¼ 8.0), 7.48–7.55 (m, 5Harom), 7.84 (2Harom, m BB0 J1 ¼ 6.5,
J2 ¼ 1.99), 7.95 (s, 1H, ¼¼CH); m/z (CIMS): 323 (Mþ). Anal.
Calcd. for C18H13NO3S (323.4): C, 66.86; H, 4.05; N, 4.33; S,
9.92. Found: C, 66.66; H, 3.94; N, 4.27; S, 9.98.
1
1176, 1143, 1072 (CAO), 840, 729, 690; H NMR (CDCl3), d,
ppm (J, Hz): 1.46 (t, 3H, CH3, J ¼ 7.0), 2.45 (s, 3H, CH3),
4.11 (q, 2H, CH2, J ¼ 7.0), 7.00 (2 Harom, m AA0 J1 ¼ 6.8, J2
¼ 1.99), 7.32 (d, 2Harom, J ¼ 8.0), 7.47 (2 Harom, m BB0 J1 ¼
6.8, J2 ¼ 1.8), 7.84 (2 Harom, m BB0 J1 ¼ 8.4, J2 ¼ 1.8), 7.89
(s, 1H, ¼¼CH); m/z (CIMS): 367 (Mþ). Anal. Calcd. for
C20H17NO4S (367.4): C, 65.38; H, 4.66; N, 3.81; S, 8.73.
Found: C, 65.18; H, 4.62; N, 3.83; S, 8.81.
5-(5-Methyl-2-furfurylidene)-3-(4-methylbenzoyl)thiazoli-
dine-2,4-dione (3e). This compound was obtained as yellow
crystals (ethanol), yield 95.2%, mp 168ꢂC (decomp.); IR, m,
cmꢁ1: 3038 (¼¼CAH), 2920 (CAH), 1758 (C¼¼O), 1711
(C¼¼O), 1681 (C¼¼O), 1611, 1513, 1438 (C¼¼C), 1412 (CAN),
5-(4-Methoxybenzylidene)-3-(4-methylbenzoyl)thiazolidine-
2,4-dione (3k). This compound was obtained as yellow crys-
tals (ethanol), yield 90.3%, mp 154ꢂC; IR, m, cmꢁ1: 3069
(¼¼CAH), 2844 (CAH), 1766 (C¼¼O), 1720 (C¼¼O), 1689
(C¼¼O), 1594, 1463 (C¼¼C), 1374 (CAN), 1290, 1151 (CAO),
1
1253, 1159, 1081 (CAO), 864, 731, 690; H NMR (CDCl3), d,
ppm (J, Hz): 2.45 (s, 3H, CH3), 6.24 (d, 1Hfuryl, J ¼ 3.5), 6.78
(d, 1Hfuryl, J ¼ 3.5), 7.32 (d, 2 Harom, J ¼ 8.0), 7.60 (s, 1H,
¼¼CH), 7.82 (d, 2Harom, J ¼ 8.4); m/z (CIMS): 327 (Mþ).
Anal. Calcd. for C17H13NO4S (327.4): C, 62.37; H, 4.00; N,
4.28; S, 9.79. Found: C, 62.09; H, 3.90; N, 4.25; S, 9.88.
5-(4-Dimethylaminobenzylidene)-3-(4-methylbenzoyl)thiazo-
lidine-2,4-dione (3f). This compound was obtained as yellow
crystals (ethanol), yield 91.8%, mp 208ꢂC (decomp.); IR, m,
cmꢁ1: 3032 (¼¼CAH), 2911, 2884 (CAH), 1751 (C¼¼O), 1714
(C¼¼O), 1680 (C¼¼O), 1585, 1530, 1441 (C¼¼C), 1379 (CAN),
1
878, 715, 689; H NMR (CDCl3), d, ppm (J, Hz): 2.45 (s, 3H,
CH3), 3.89 (s, 3H, AOCH3), 7.01 (2Harom, m AA0 J1 ¼ 6.8, J2
¼ 1.99), 7.32 (d, 2Harom, J ¼ 8.4), 7.50 (2Harom, m BB0 J1 ¼
7.0, J2 ¼ 1.99), 7.83 (d, 2Harom, J ¼ 8.2), 7.89 (s, 1H, ¼¼CH);
m/z (CIMS): 353 (Mþ). Anal. Calcd. for C19H15NO4S (353.4):
C, 64.57; H, 4.28; N, 3.96; S, 9.07. Found: C, 64.29; H, 4.18;
N, 3.94; S, 9.108.
Journal of Heterocyclic Chemistry
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K. M. Popov-Pergal, D. Poleti, M. P. Rancic, A. Meden, and M. V. Pergal
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Vol 47
[8] Momose, Y.; Kanji, M.; Hitoshi, I.; Chitoshi, H.; Satoru,
O.; Takashi, S. Chem Pharm Bull 1991, 39, 1440.
SUPPLEMENTARY DATA
CCDC 733926 contains the supplementary crystallo-
graphic data for this article. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/conts/retrie-
ving.html (or from the Cambridge Crystallographic Data
Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:
þ44 1223 336033; or deposit@ccdc.cam.ac.uk).
[9] Takashi, S.; Katsutoshi, M.; Momose, Y.; Hitoshi, I.; Take-
shi, F.; Kanji, M. J Med Chem 1992, 35, 2617.
´
[10] Tomita, M.; Shindo, N.; Hirakata, K. Kaken Pharm Co Ltd.
Patent JO 3077–875–A, 1991.
[11] Kobori, T.; Yamamoto, R.; Fujita, M.; Hiyama, T.; Nagate,
T. Taisho Pharm Co Ltd. Patent WO 9207840–A1, 1992.
[12] Brown, F. G. Chem Rev 1961, 61, 463.
[13] Singh, S. P.; Parmar, S. S.; Raman, K.; Stenberg, V. I.
Chem Rev 1981, 81, 175.
Acknowledgment. This work was supported by a research
grant from the Ministry of Science and Technological
Development of the Republic of Serbia (Grant No. 1694,
142030, and 142023).
[14] Tsujie, M.; Nakamori, S.; Okami, J.; Hayashi, N.; Hiraoka,
N.; Nagano, H.; Dono, K.; Umeshita, K.; Sakon, M.; Monden, M. Exp
Cell Res 2003, 289, 143.
[15] Gupta, S.; Tsukamoto, M.; Pulman, D. A.; Ying, B-P.; Wu,
S-Y. Patent WO 9,921,837, 1999.
[16] Gupta, S.; Wu, S–Y.; Tsukamoto, M.; Pulman, D. A.; Ying,
B–P. Patent US 6,355,799, 2002.
REFERENCES AND NOTES
[17] Yamamoto, T.; Takamatsu, M.; Kawahara, T. Patent JP
63,264,574, 1988.
[1] Lima, M. C. A.; Deise, L. B.; Goes, A. J. S.; Suely, L. G.;
Pitta, I. R. Pharmazie 1992, 47, 182.
ˇ
´
[18] Popov-Pergal, K.; Cekovic, Z.; Pergal, M. Zh Obshch Khim
1991, 61, 2112.
[19] Popov-Pergal, K.; Cekovic, Z.; Pergal, M. Sulphur Lett
1989, 9, 95.
[2] El-Feky, S. A. H. Pharmazie 1992, 48, 894.
[3] Strumvoll, M.; Haring, H. U. Ann Med 2002, 34, 217.
[4] Unangst, P. C.; Connor, W. A.; Sorenson, R. J.; Sircar, J.
C.; Wright, C. D.; Schrier, D. J.; Dyer, R. D. Bioorg Med Chem Lett
1993, 3, 1729.
ˇ
´
´
[20] Divjakovic, V.; Popov-Pergal, K.; Pergal, M.; Klement, U.
Acta Crystallogr 1991, C47, 1760.
[5] Hossain, U.; Bhattacharia, S. Bioorg Med Chem Lett 2007,
17, 1149.
[21] Drew, M. G. B.; Mok, K. F.; Ang, K. P.; Tan, S. F. Acta
Crystallogr 1987, C43, 743.
[6] Chandrappa, S.; Benaka Prasad, S. B.; Vinaya, K.; Ananda
Kumar, C. S.; Thimmegowda, N. R.; Rangappa, K. S. Invest New
Drugs 2008, 26, 437.
[22] Form, G. R.; Raper, S.; Downie, T. C. Acta Crystallogr
1975, B31, 2181.
[7] Musial, L.; Staniec. J. Roczniki Chemii 1965, 39, 839.
[23] Farrugia, L. J. J Appl Cryst 1999, 32, 837.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet