Design, synthesis and characterization of some novel 3-coumarinyl- 5-aryliden-1,3-thiazolidine-2,4-diones and their antioxidant activity

Article abstract of DOI:10.1515/znb-2011-0210

In our effort to obtain biologically active compounds, new 3,5-disubstituted 1,3-thiazolidine-2,4- diones (5a - r) were synthesized. A series of 5-arylmethylidene-1,3-thiazolidine-2,4-diones (3a - r) were prepared by Knoevenagel reaction from 1,3-thiazolidine-2,4-dione (2) and appropriate aromatic aldehydes. Condensation of 3a - r with 7-hydroxy-4-bromomethyl-2-oxo- 2H-chromene (1) afforded novel 3-(7-hydroxy-2-oxo-2H-chromen-4-ylmethyl)-5- arylidene-1,3-thiazolidine-2,4-diones 5a - r. Compounds 3a - r and 5a - r were evaluated for their antioxidant activity (DPPH free radical scavenging activity).

Full text of DOI:10.1515/znb-2011-0210

Design, Synthesis and Characterization of Some Novel 3-Coumarinyl-
5-aryliden-1,3-thiazolidine-2,4-diones and Their Antioxidant Activity
ˇ
Milan Cacˇic´ and Maja Molnar
Department of Applied Chemistry and Ecology, Faculty of Food Technology,
J. J. Strossmayer University, Franje Kuhacˇa 20, 31 000 Osijek, Croatia
ˇ
Reprint requests to Dr. Milan Cacˇic´. Fax: 00385 31 207 115. E-mail: mcacic@ptfos.hr
Z. Naturforsch. 2011, 66b, 177 – 183; received September 29, 2010
In our effort to obtain biologically active compounds, new 3,5-disubstituted 1,3-thiazolidine-2,4-
diones (5a – r) were synthesized. A series of 5-arylmethylidene-1,3-thiazolidine-2,4-diones (3a – r)
were prepared by Knoevenagel reaction from 1,3-thiazolidine-2,4-dione (2) and appropriate aromatic
aldehydes. Condensation of 3a – r with 7-hydroxy-4-bromomethyl-2-oxo-2H-chromene (1) afforded
novel 3-(7-hydroxy-2-oxo-2H-chromen-4-ylmethyl)-5-arylidene-1,3-thiazolidine-2,4-diones 5a – r.
Compounds 3a – r and 5a – r were evaluated for their antioxidant activity (DPPH free radical scav-
enging activity).
Key words: 1,3-Thiazolidine-2,4-diones, 7-Hydroxy-4-bromomethyl-2-oxo-2H-chromene,
Knoevenagel Reaction, N-Substitution, Antioxidant Activity
Introduction
yl) radical significantly in a concentration-dependent
manner.
Natural coumarins affect the formation and scav-
enging of reactive oxygen species (ROS) and influ-
ence free radical-mediated oxidative damage [16]. The
styryl carbonyl moiety in the coumarin skeleton is ex-
pected to affect scavenging of reactive substances de-
rived from oxygen and to influence the process involv-
ing free radical-mediated injury [17].
Based upon the above considerations, it seemed
worthy to design and synthesize certain new hetero-
cyclic compounds containing the 1,3-thiazolidine-2,4-
dione moiety and the coumarin unit in one frame.
1,3-thiazolidine-2,4-dione is used as a starting ma-
terial for the synthesis of drugs. In heterocyclic chem-
istry, the class of 1,3-thiazolidine-2,4-diones is par-
ticularly important as therapeutic agents and have
been thoroughly investigated as peroxisome pro-
liferator-activated receptor-γ-antagonists (PPAR-γ-an-
tagonists), leading to the development of several
insulin-sensitizing drugs for the treatment of diabetes
type-2.
Extensive interest has been focused on 1,3-thiazo-
lidine-2,4-dione derivatives which have been shown
to possess a broad spectrum of biological activ-
ities. The most important of these are antidia-
betic [1,2], analgesic [3], cardiotonic [4], antibac-
terial, antifungal [5–8], antimicrobial [9], anticon-
vulsant [10], and cyclooxygenase and lipoxyge-
nase inhibitory [11] activities. 1,3-thiazolidine-2,4-
dione derivatives were investigated as templates for
the design and synthesis of novel and safe anti-
inflammatory compounds [12, 13]. Multi-substituted
benzylidenethiazolidine-2,4-diones have also been
proven to be potent antioxidants [14]. Hossain
and Bhattacharya [15] have synthesized a series
of 5-arylidene-2,4-thiazolidinediones and their ger-
anyloxy or prenyloxy derivatives; all compounds
scavenged the DPPH (1,1-diphenyl-2-picryhydraz-
Results and Discussion
The synthetic routes followed in the preparation of
the new compounds are illustrated in Schemes 1 – 3.
The products are listed in Table 1. Compound 1 was
synthesized from ethyl 4-bromoacetoacetate and resor-
◦
cinol in conc. sulfuric acid at −10 C, according to
the literature method [18] (Scheme 1). 1,3-thiazolid-
ine-2,4-dione (2) was obtained from monochloroacetic
acid and thiourea in hot water [7], and yielded up on
Knoevenagel condensation [19] with substituted aro-
matic aldehydes the 5-arylmethylidene-1,3-thiazolid-
ine-2,4-diones 3a – r (Scheme 2). A series of novel
3,5-disubstituted 1,3-thiazolidin-2,4-diones 5a – r was
c
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178
M. Cacˇic´ – M. Molnar · 3-Coumarinyl-5-aryliden-1,3-thiazolidine-2,4-diones
Scheme 1. Reagents and conditions:
◦
(i) Br2, CHCl3 or CH2Cl2, 0 C, stir-
ring, 15 h, r. t.; (ii) H2SO4 conc.,
−10 ◦C, 2 to 4 d, r. t.
Scheme 2. Reagents and conditions:
(i) HCl conc., reflux, 10 h; (ii) aro-
matic aldehydes, piperidine, ethanol, re-
flux, 24 h.
Scheme 3. Reagents and conditions:
(i) K2CO3, DMF, r. t., 6 h; (ii) aromatic
aldehydes, piperidine, ethanol, reflux,
24 h.
Table 1. Compounds 3
and 5 synthesized.
3, 5
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Ar
and mass spectral data. The IR spectra of compounds
5a – r showed bands at 3300– 3420 (7-OH coum.
and arom. stretching), 3120 (CH aromatic stretching),
3002 (CH stretching, vinyl), 2925 and 2785 (aliphatic
asymmetric and symmetric stretching, respectively),
1726– 1670 (α-pyrone C=O stretching), 1587, 1608 –
1654 (C=C stretching), 1313 (C–N stretching), 1253 –
1270 (C–O–C stretching), and 748 – 783 cm−1 (C–S–
C stretching).
The 1H NMR spectrum for compound 4 shows sin-
glet signals for the NCH2 protons at δ = 4.86 ppm and
for the ring-CH2 protons at 4.37 ppm. After Knoeve-
nagel condensation, compounds 5a – r were obtained.
In the 1H NMR spectra of these products the signal for
the ring-CH2 protons is absent. In the mass spectra, all
the compounds gave [M–H]+ ion peaks.
phenyl
2-hydroxyphenyl
3-hydroxyphenyl
4-hydroxyphenyl
2-methoxyphenyl
3-methoxyphenyl
4-methoxyphenyl
2-chlorophenyl
3-bromophenyl
4-bromophenyl
4-fluorophenyl
3-phenoxyphenyl
4-N,N-dimethylaminophenyl
styryl
2,4-dihydroxyphenyl
3,4-dihydroxyphenyl
4-hydroxy-3-methoxyphenyl
3,4,5-trimethoxyphenyl
obtained by condensation of compounds 3a – r with 1
(Scheme 3). N-Substitution [20] of 1,3-thiazolidin-2,4-
diones 2 with 7-hydroxy-4-bromomethyl-2-oxo-2H-
chromene (1) in DMF/K2CO3 furnished thiazolidine-
2,4-dione derivative 4, which on Knoevenagel conden-
sation with substituted aromatic aldehydes yielded the
same compounds 5a – r (Scheme 3).
Antioxidant assay
The DPPH free radical, bearing an odd electron,
gives a strong absorption maximum at λ = 517 nm and
is purple in color. When the odd electron of the DPPH
radical pairs with a hydrogen atom from a free radical
scavenging antioxidant, the reduced form DPPH-H is
The constitution of the synthesized compounds was created, and the color turns from purple to yellow. The
elucidated by elemental analysis, FT IR, 1H NMR method used in our work applies to the overall antioxi-
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M. Cacˇic´ – M. Molnar · 3-Coumarinyl-5-aryliden-1,3-thiazolidine-2,4-diones
179
Fig. 1. Scavenging activity on DPPH (%) of the tested compounds, compared to the scavenging activity of ascorbic acid (AA).
dant capacity of the sample after 30 min of incubation. enging activity, with the exception of 3o. These com-
The DPPH-scavenging activity was determined against pounds also possess an olefinic bond and an NH group
ascorbic acid as the standard compound.
in the thiazolidinedione moiety, which can also con-
tribute to the radical scavenging activity [15].
Antioxidant activity
Conclusion
The data given in Fig. 1 show that substituents on the
phenyl ring have a great influence on the antioxidant
activity. The DPPH-scavenging activity of the com-
pounds showing the best results in descending order
was found to be: 5p > 3p > 5q > 3q > 3o.
In this study antioxidant properties of the 5-aryl-
methylidene-1,3-thiazolidine-2,4-diones 3a – r and of
the novel 3-(7-hydroxy-2-oxo-2H-chromen-4-ylmeth-
yl)-5-arylidene-1,3-thiazolidine-2,4-diones5a – r were
examined. Some of the compounds show excellent
DPPH scavenging properties.
The compound showing the best DPPH scaveng-
ing activity was 5p with a 3,4-(OH)2-substitued phenyl
ring, followed by 3p with the same substituents on the
phenyl ring. Compounds 5q and 3q with 3-OCH3-4-
OH substituents on the phenyl ring also showed very
good antioxidant activity. All of these compounds pos-
sess a free hydroxyl group in p-position of the phenyl
ring, which can donate a hydrogen atom, and another
electron-donating group in m-position, the presence
of which obviously enhances the scavenging activity.
Lin et al. [21] showed that radical-scavenging effects
of coumarins were correlated with the number of hy-
droxyl groups, the presence of a free hydroxyl group in
a phenyl ring influencing the scavenging activity [22].
Substituents on the phenyl ring, as well as their posi-
tion, had a greater influence on the free radical scav-
enging activity than the presence of the coumarin moi-
ety attached to the 5-arylmethylidene-1,3-thiazolidine-
2,4-dione core. However, in a comparison of com-
pounds with the same substituent pattern in the series
Experimental Section
General information
The melting points were taken on an Electrothermal Cap-
illary melting point apparatus and are uncorrected. Thin-
layer chromatographies were performed using fluorescent
silica gel plates HF254 Merck, which were examined under
UV light (254 and 365 nm), using benzene / acetone / acetic
acid (8 : 1 : 1) as eluent. Silica gel (230 – 400 mesh) was used
for flash chromatography separations. The elemental anal-
yses for C, H and N were carried out on a Perkin-Elmer
Analyzer 2440. Infrared spectra (ν in cm−1) were recorded
on a Shimadzu FT-IR 8400 S instrument, using KBr disks.
1H NMR spectra were recorded on a Jeol EX-270 MHz
NMR spectrometer at 293 K in [D6]DMSO. Spectra were
internally referenced to TMS. Peaks are reported in ppm
downfield of TMS. The mass spectra were recorded on an
LC/MS/MS (API 2000) Applied Biosystems instrument. The
absorbance was measured on a UV/Vis spectrophotometer
3a – r vs. 5a – r, the latter ones showed a better scav- Helios γ (Thermo Spectronic, Cambridge UK).
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180
M. Cacˇic´ – M. Molnar · 3-Coumarinyl-5-aryliden-1,3-thiazolidine-2,4-diones
General procedure for preparation of 5-arylidene-1,3-thiaz- (Z)-5-(3-hydroxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-
olidine-2,4-diones 3a – r [19]
chromen-4-yl)methyl]thiazolidine-2,4-dione (5c)
◦
M. p. 287 C. – Rf = 0.48. – Yield 76 %. – FT-IR (KBr):
An appropriate aromatic aldehyde (5 mmol) was added to
a stirred mixture of 1,3-thiazolidine-2,4-dione (2) (5 mmol)
and piperidine (4 mmol) in ethanol (8.5 mL). The reac-
tion mixture was refluxed for 24 h until the starting com-
pounds had completely disappeared as monitored by TLC
using benzene / acetone / acetic acid (8 : 1 : 1). The reaction
mixture was poured into water, and acetic acid was added
dropwise till acidic to litmus paper. The precipitated product
was filtered, washed with water, and crystallized from the
appropriate solvent to give pure compounds 3a – r.
νmax = 3282, 3082, 2820, 1737, 1678, 1604, 1575, 1494,
1415, 1381, 1315, 1276, 1143 and 769 cm−1. – 1H NMR:
δ = 5.02 (s, 2H, CH2, coum.), 5.96 (s, 1H, 3-H, coum.), 6.77
(s, 1H, 8-H, coum.), 6.84 (d, 1H, 5-H, coum.), 6.92 – 7.51
(m, 4H, arylidene), 7.72 (d, 1H, 6-H, coum.), 7.91 (s, 1H,
-HC=C-), 10.08 (s, 1H, OH, coum.), 13.33 (s, 1H, OH, aryli-
dene). – MS: m/z = 394.1 [M–H]+. – Anal. for C20H13NO6S
(395.05): calcd. C 60.75, H 3.31, N 3.54, S 8.11; found
C 60.72, H 3.34, N 3.57, S 8.08 %.
(Z)-5-(4-hydroxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5d)
General procedure for preparation of 3-(7-hydroxy-2-
oxo-2H-chromen-4-ylmethyl)-5- arylidene-1,3-thiazolidine-
2,4-diones 5a – r [20]
◦
M. p. 295 C. – Rf = 0.52. – Yield 78 %. – FT-IR (KBr):
νmax = 3350, 3203, 2929, 2816, 1720, 1685, 1598, 1512,
1415, 1379, 1327, 1284, 1149, 1089, 985 and 731 cm−1. –
1H NMR: δ = 5.02 (s, 2H, CH2, coum.), 5.96 (s, 1H, 3-H,
coum.), 6.76 (s, 1H, 8-H, coum.), 6.86 (d, 1H, 5-H, coum.),
6.93 (d, 2H, arylidene), 7.54 (d, 2H, arylidene), 7.72 (d,
1H, 6-H, coum.), 7.90 (s, 1H, -HC=C-), 10.05 (s, 1H, OH,
coum.), 13.38 (s, 1H, OH, arylidene). – MS: m/z = 394.0
[M–H]+. – Anal. for C20H13NO6S (395.05): calcd. C 60.75,
H 3.31, N 3.54, S 8.11; found C 60.74, H 3.33, N 3.50,
S 8.13 %.
An equimolar mixture of 5-arylidene-1,3-thiazolidine-
2,4-diones 3a – r (10.0 mmol), 7-hydroxy-4-bromomethyl-2-
oxo-2H-chromene (1), (10.0 mmol) and anhydrous K2CO3
(10.0 mmol) was stirred at room temperature in DMF
(10 mL) for 6 h. The reaction mixture was poured into
crushed ice/water. The precipitated product was filtered,
washed with water and crystallized from methanol. Pure
compounds 5a – r were obtained.
(Z)-5-Benzylidene-3-[(7-hydroxy-2-oxo-2H-chromen-4-yl)-
methyl]thiazolidine-2,4-dione (5a)
(Z)-5-(2-Methoxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5e)
◦
M. p. 270 C. – Rf = 0.52. – Yield 61 %. – FT-IR (KBr):
νmax = 3398, 3082, 1689, 1595, 1414, 1384, 1323, 1282,
1124, 981 and 769 cm−1. – 1H NMR: δ = 5.02 (s, 2H,
CH2, coum.), 5.96 (s, 1H, 3-H, coum.), 6.76 (s, 1H, 8-H,
coum.), 6.86 (d, 1H, 5-H, coum.), 6.90 – 7.54 (m, 5H, aryli-
dene), 7.71 (d, 1H, 6-H, coum.), 7.94 (s, 1H, -HC=C-), 10.03
(s, 1H, OH, coum.). – MS: m/z = 377.9 [M–H]+. – Anal.
for C20H13NO5S (379.05): calcd. C 63.32, H 3.45, N 3.69,
S 8.45; found C 63.30, H 3.47, N 3.71, S 8.40 %.
◦
M. p. 306 C. – Rf = 0.51. – Yield 74 %. – FT-IR (KBr):
νmax = 3367, 3080, 2926, 2839, 1722, 1705, 1678, 1612,
1592, 1570, 1485, 1417, 1377, 1313, 1257, 1143, 1020, 840
and 748 cm−1. – 1H NMR: δ = 3.85 (s, 3H, OCH3), 5.03 (s,
2H, CH2, coum.), 6.02 (s, 1H, 3-H, coum.), 6.77 (s, 1H, 8-H,
coum.), 6.86 (d, 1H, 5-H, coum.), 7.12 – 7.66 (m, 4H, aryli-
dene), 7.74 (d, 1H, 6-H, coum.), 7.97 (s, 1H, -HC=C-), 10.35
(s, 1H, OH, coum.). – MS: m/z = 408.1 [M–H]+. – Anal.
for C21H15NO6S (409.06): calcd. C 61.61, H 3.69, N 3.42,
S 7.83; found C 61.59, H 3.71, N 3.40, S 7.81 %.
(Z)-5-(2-hydroxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5b)
(Z)-5-(3-Methoxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5f)
◦
M. p. 229 C. – Rf = 0.46. – Yield 74 %. – FT-IR (KBr):
νmax = 3412, 3315, 3082, 2922, 1724, 1701, 1676, 1612,
◦
M. p. 279 C. – Rf = 0.56. – Yield 81 %. – FT-IR (KBr):
1572, 1458, 1379, 1313, 1257, 1145 and 750 cm−1. – 1H
NMR: δ = 5.01 (s, 2H, CH2, coum.), 5.95 (s, 1H, 3-H, νmax = 3298, 3082, 2972, 2928, 1737, 1705, 1678, 1608,
coum.), 6.76 (s, 1H, 8-H, coum.), 6.86 (d, 1H, 5-H, coum.), 1560, 1489, 1379, 1417, 1381, 1307, 1274, 1145, 1003 and
6.93 – 7.55 (m, 4H, arylidene), 7.72 (d, 1H, 6-H, coum.), 784 cm−1. – 1H NMR: δ = 3.85 (s, 3H, OCH3), 5.03 (s,
7.90 (s, 1H, -HC=C-), 10.05 (s, 1H, OH, coum.), 13.34 (s, 2H, CH2, coum.), 6.02 (s, 1H, 3-H, coum.), 6.77 (s, 1H, 8-H,
1H, OH, arylidene). – MS: m/z = 394.7 [M–H]+. – Anal. coum.), 6.86 (d, 1H, 5-H, coum.), 7.12 – 7.66 (m, 4H, aryli-
for C20H13NO6S (395.05): calcd. C 60.75, H 3.31, N 3.54, dene), 7.74 (d, 1H, 6-H, coum.), 7.97 (s, 1H, -HC=C-), 10.35
S 8.11; found C 60.71, H 3.29, N 3.50, S 8.14 %.
(s, 1H, OH, coum.). – MS: m/z = 408.1 [M–H]+. – Anal.
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M. Cacˇic´ – M. Molnar · 3-Coumarinyl-5-aryliden-1,3-thiazolidine-2,4-diones
181
for C21H15NO6S (409.06): calcd. C 61.61, H 3.69, N 3.42, Anal. for C20H12BrNO5S (456.96): calcd. C 52.42, H 2.64,
S 7.83; found C 61.60, H 3.70, N 3.44, S 7.80 %.
N 3.06, S 7.00; found C 52.40, H 2.65, N 3.02, S 7.02 %.
(Z)-5-(4-Methoxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-
(Z)-5-(4-Bromobenzylidene)-3-[(7-hydroxy-2-oxo-2H-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5g)
chromen-4-yl)methyl]thiazolidine-2,4-dione (5k)
◦
M. p. 287 ◦C. – Rf = 0.62. – Yield 78 %. – FT-IR
M. p. 284 C. – Rf = 0.59. – Yield 80 %. – FT-IR (KBr):
(KBr): νmax = 3412, 3068, 3014, 2933, 2640, 1726, 1680, νmax = 3433, 3088, 2937, 2703, 1720, 1691, 1649, 1604,
1593, 1551, 1413, 1379, 1332, 1253, 1182, 1149, 1022 and 1423, 1373, 1336, 1273, 1151, 1072 and 762 cm−1. –
769 cm−1. – 1H NMR: δ = 3.85 (s, 3H, OCH3), 5.03 (s, 1H NMR: δ = 5.02 (s, 2H, CH2, coum.), 5.96 (s, 1H,
2H, CH2, coum.), 6.00 (s, 1H, 3-H, coum.), 6.77 (s, 1H, 8-H, 3-H, coum.), 6.76 (s, 1H, 8-H, coum.), 6.86 (d, 1H, 5-H,
coum.), 6.84 (d, 1H, 5-H, coum.), 7.12 (d, 2H, arylidene), coum.), 6.94 (d, 2H, arylidene), 7.64 (d, 2H, arylidene),
7.65 (d, 2H, arylidene), 7.74 (d, 1H, 6-H, coum.), 7.96 (s, 7.72 (d, 1H, 6-H, coum.), 7.90 (s, 1H, -HC=C-), 10.38 (s,
1H, -HC=C-), 10.66 (s, 1H, OH, coum.). – MS: m/z = 408.0 1H, OH, coum.). – MS: m/z = 457.8 [M–H]+. – Anal. for
[M–H]+. – Anal. for C21H15NO6S (409.06): calcd. C 61.61, C20H12BrNO5S (456.96): calcd. C 52.42, H 2.64, N 3.06,
H 3.69, N 3.42, S 7.83; found C 61.61, H 3.60, N 3.41, S 7.00; found C 52.41, H 2.65, N 3.08, S 6.98 %.
S 7.82 %.
(Z)-5-(3-Phenoxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-
(Z)-5-(2-Chlorobenzylidene)-3-[(7-hydroxy-2-oxo-2H-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5h)
chromen-4-yl)methyl]thiazolidine-2,4-dione (5l)
◦
M. p. 200 C. – Rf = 0.64. – Yield 84 %. – FT-IR (KBr):
◦
M. p. 265 C. – Rf = 0.55. – Yield 54 %. – FT-IR (KBr): νmax = 3434, 3267, 3135, 3062, 2931, 1724, 1608, 1487,
νmax = 3412, 3070, 2928, 1687, 1608, 1417, 1375, 1323, 1414, 1375, 1317, 1257, 1141, 997 and 777 cm−1. – 1H
1271, 1138, 1041, 852 and 758 cm−1. – 1H NMR: δ = 5.02 NMR: δ = 5.01 (s, 2H, CH2, coum.), 5.98 (s, 1H, 3-H,
(s, 2H, CH2, coum.), 5.96 (s, 1H, 3-H, coum.), 6.76 (s, 1H, coum.), 6.75 (s, 1H, 8-H, coum.), 6.86 (d, 1H, 5-H, coum.),
8-H, coum.), 6.86 (d, 1H, 5-H, coum.), 6.94 – 7.56 (m, 4H, 6.93 – 7.58 (m, 9H, arylidene), 7.72 (d, 1H, 6-H, coum.), 7.92
arylidene), 7.72 (d, 1H, 6-H, coum.), 7.94 (s, 1H, -HC=C-), (s, 1H, -HC=C-), 10.25 (s, 1H, OH, coum.). – MS: m/z =
10.55 (s, 1H, OH, coum.). – MS: m/z = 411.8 [M–H]+. – 470.0 [M–H]+. – Anal. for C26H17NO6S (471.08): calcd.
Anal. for C20H12ClNO5S (413.01): calcd. C 58.05, H 32.92, C 66.23, H 3.63, N 2.97, S 6.80; found C 66.20, H 3.65,
N 3.38, S 7.75; found C 58.00, H 32.94, N 3.39, S 7.71 %.
N 2.98, S 6.81 %.
(Z)-5-(4-Fluorobenzylidene)-3-[(7-hydroxy-2-oxo-2H-
(Z)-5-[4-(Dimethylamino)benzylidene]-3-[(7-hydroxy-2-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5i)
oxo-2H-chromen-4-yl)methyl]thiazolidine-2,4-dione (5m)
◦
M. p. 252 C. – Rf = 0.53. – Yield 65 %. – FT-IR (KBr):
M. p. > 300 ◦C. – Rf = 0.50. – Yield 79 %. – FT-IR (KBr):
νmax = 3398, 3064, 2935, 1724, 1678, 1595, 1512, 1418, νmax = 3435, 3088, 2926, 2813, 1726, 1678, 1606, 1575,
1383, 1323, 1282, 1151 and 740 cm−1. – 1H NMR: δ = 5.02 1525, 1444, 1408, 1371, 1151, 1097 and 713 cm−1. – 1H
(s, 2H, CH2, coum.), 5.96 (s, 1H, 3-H, coum.), 6.76 (s, 1H, NMR: δ = 2.84 (s, 6H, N(CH3)2), 5.02 (s, 2H, CH2, coum.),
8-H, coum.), 6.86 (d, 1H, 5-H, coum.), 6.96 (d, 2H, aryli- 5.96 (s, 1H, 3-H, coum.), 6.76 (s, 1H, 8-H, coum.), 6.86 (d,
dene), 7.58 (d, 2H, arylidene), 7.72 (d, 1H, 6-H, coum.), 7.90 1H, 5-H, coum.), 6.95 (d, 2H, arylidene), 7.56 (d, 2H, aryli-
(s, 1H, -HC=C-), 10.35 (s, 1H, OH, coum.). – MS: m/z = dene), 7.73 (d, 1H, H-6, coum.), 7.95 (s, 1H, -HC=C-), 10.55
395.9 [M–H]+. – Anal. for C20H12FNO5S (397.04): calcd. (s, 1H, OH, coum.). – MS: m/z = 421.1 [M–H]+. – Anal.
C 60.45, H 3.04, N 3.52, S 8.07; found C 60.47, H 3.03, for C22H18N2O5S (422.09): calcd. C 62.55, H 4.29, N 6.63,
N 3.50, S 8.09 %.
S 7.59; found C 62.53, H 4.31, N 6.60, S 7.60 %.
(Z)-5-(3-Bromobenzylidene)-3-[(7-hydroxy-2-oxo-2H-
(Z)-5-(4-hydroxy-3-methoxybenzylidene)-3-[(7-hydroxy-2-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5j)
oxo-2H-chromen-4-yl)methyl]thiazolidine-2,4-dione (5n)
◦
◦
M. p. 276 C. – Rf = 0.54. – Yield 82 %. – FT-IR (KBr):
M. p. 257 C. – Rf = 0.51. – Yield 80 %. – FT-IR (KBr):
νmax = 3396, 3305, 3066, 2929, 1718, 1680, 1606, 1560, νmax = 3365, 3080, 2924, 1701, 1687, 1610, 1570, 1516,
1419, 1381, 1315, 1136 and 783 cm−1. – 1H NMR: δ = 5.02 1417, 1377, 1284, 1139 and 794 cm−1. – 1H NMR: δ = 3.73
(s, 2H, CH2, coum.), 5.96 (s, 1H, 3-H, coum.), 6.76 (s, 1H, (s, 3H, OCH3), 5.02 (s, 2H, CH2, coum.), 5.96 (s, 1H, 3-H,
8-H, coum.), 6.86 (d, 1H, 5-H, coum.), 6.93 – 7.58 (m, 4H, coum.), 6.76 (s, 1H, 8-H, coum.), 6.86 (d, 1H, 5-H, coum.),
arylidene), 7.72 (d, 1H, 6-H, coum.), 7.90 (s, 1H, -HC=C-), 6.92 – 7.55 (m, 3H, arylidene), 7.74 (d, 1H, 6-H, coum.),
10.45 (s, 1H, OH, coum.). – MS: m/z = 457.8 [M–H]+. – 7.94 (s, 1H, -HC=C-), 10.05 (s, 1H, OH, coum.), 10.48 (s,
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182
M. Cacˇic´ – M. Molnar · 3-Coumarinyl-5-aryliden-1,3-thiazolidine-2,4-diones
1H, OH, arylidene). – MS: m/z = 424.1 [M–H]+. – Anal. [M–H]+. – Anal. for C23H19NO8S (469.08): calcd. C 58.84,
for C21H15NO7S (425.06): calcd. C 59.29, H 3.55, N 3.29, H 4.08, N 2.98, S 6.83; found C 58.83, H 4.09, N 2.96,
S 7.54; found C 59.28, H 3.54, N 3.30, S 7.57 %.
S 6.84 %.
(Z)-5-(2,4-Dihydroxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5o)
(Z)-5-[(E)-3-Phenylallylidene]-3-[(7-hydroxy-2-oxo-2H-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5r)
M. p. > 300 ◦C. – Rf = 0.47. – Yield 62 %. – FT-IR
(KBr): νmax = 3412, 3315, 3082, 2922, 2853, 1724, 1701,
1676, 1612, 1572, 1458, 1379, 1417, 1313, 1257, 1145 and
M. p. 244 ◦C. – Rf = 0.50. – Yield 48 %. – FT-IR
(KBr): νmax = 3412, 3315, 3082, 2922, 2853, 1724, 1701,
1676, 1612, 1572, 1458, 1379, 1417, 1313, 1257, 1145 and
750 cm−1. – 1H NMR: δ = 5.02 (s, 2H, CH2, coum.),
5.96 (s, 1H, 3-H, coum.), 6.76 (s, 1H, 8-H, coum.), 6.86
(d, 1H, 5-H, coum.), 6.92 – 7.56 (m, 5H, arylidene), 7.72 (d,
1H, 6-H, coum.), 7.94 – 8.01 (m, 3H, -HC=CH-CH=), 10.55
(s, 1H, OH, coum). – MS: m/z = 404.0 [M–H]+. – Anal.
for C22H15NO5S (405.42): calcd. C 65.18, H 3.73, N 3.45,
S 7.91; found C 65.16, H 3.75, N 3.46, S 7.90 %.
1
750 cm−1. – H NMR: δ = 5.02 (s, 2H, CH2, coum.), 5.96
(s, 1H, 3-H, coum.), 6.76 (s, 1H, 8-H, coum.), 6.86 (d, 1H,
5-H, coum.), 6.90 – 7.57 (m, 4H, arylidene), 7.72 (d, 1H, 6-H,
coum.), 7.95 (s, 1H, -HC=C-), 10.45 (s, 1H, OH, coum.),
10.68 (s, 2H, OH, arylidene). – MS: m/z = 410.1 [M–H]+. –
Anal. for C20H13NO7S (411.04): calcd. C 58.39, H 3.19,
N 3.40, S 7.79; found C 58.40, H 3.17, N 3.42, S 7.81 %.
(Z)-5-(3,4-Dihydroxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-
chromen-4-yl)methyl]thiazolidine-2,4-dione (5p)
Scavenging of the 1,1-diphenyl-2-picrylhydrazyl radical
Determination of the antioxidant activity was performed
according to the procedure described in the literature [24,25]
with some modifications. DMSO was used as a solvent [23],
due to the low solubility of the synthesized compounds in
ethanol and methanol.
0.75 mL of a DMSO solution of a synthesized compound
(0.2 mM) was added to a DMSO solution of the DPPH rad-
ical (0.2 mM), so that the final concentration of DPPH rad-
ical and the synthesized compound was 0.1 mM. The mix-
ture was shaken and allowed to stand at r. t. After 30 min the
absorbance at λ = 517 nm was determined, and the scaveng-
ing activity was calculated according to the formula below.
Ascorbic acid was used as a reference compound.
◦
M. p. 235 C. – Rf = 0.42. – Yield 55 %. – FT-IR (KBr):
νmax = 3367, 3091, 3022, 2924, 1734, 1676, 1610, 1585,
1518, 1415, 1381, 1300, 1205, 1145 and 733 cm−1. – 1H
NMR: δ = 5.01 (s, 2H, CH2, coum.), 5.97 (s, 1H, 3-H,
coum.), 6.76 (s, 1H, 8-H, coum.), 6.87 (d, 1H, 5-H, coum.),
6.93 – 7.55 (m, 4H, arylidene), 7.72 (d, 1H, 6-H, coum.),
7.95 (s, 1H, -HC=C-), 10.45 (s, 1H, OH, coum.), 10.58 (s,.
2H, OH, arylidene). – MS: m/z = 410.0 [M–H]+. – Anal.
for C20H13NO7S (411.04): calcd. C 58.39, H 3.19, N 3.40,
S 7.79; found C 58.38, H 3.21, N 3.41, S 7.81 %.
(Z)-5-(3,4,5-Trimethoxybenzylidene)-3-[(7-hydroxy-2-
oxo-2H-chromen-4-yl)methyl]thiazolidine-2,4-dione (5q)
Ab+As−Am
◦
M. p. 185 C. – Rf = 0.59. – Yield 86 %. – FT-IR (KBr):
scavenging activity (%) =
×100
Ab
νmax = 3379, 3084, 2972, 1737, 1689, 1607, 1466, 1413,
1373, 1323, 1143, 972 and 732 cm−1. – 1H NMR: δ = 3.76 Ab – absorbance of a 0.1 mM DMSO solution of the DPPH
(s,9H, OCH3), 5.02 (s, 2H, CH2, coum.), 5.96 (s, 1H, 3-H, radical at λ= 517 nm; As – absorbance of a 0.1 mM DMSO
coum.), 6.77 (s, 1H, 8-H, coum.), 6.86 (d, 1H, 5-H, coum.), solution of the test compound at λ = 517 nm; Am – ab-
6.98 (s, 2H, arylidene), 7.72 (d,1H, 6-H, coum.), 7.96 (s, sorbance of the DMSO mixture of the test compound and
1H, -HC=C-), 10.15 (s, 1H, OH, coum.). – MS: m/z = 468.1 the DPPH radical at λ = 517 nm.
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M. Cacˇic´ – M. Molnar · 3-Coumarinyl-5-aryliden-1,3-thiazolidine-2,4-diones
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