Synthesis, Characterization, Antibacterial, and Antifungal Activity of Novel 2-(2-hydroxy-5-((aryl)-diazenyl)phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one

Article abstract of DOI:10.1002/jhet.2620

A series of novel thiazolidinones, that is, 2-(2-hydroxy-5-((aryl)-diazenyl)phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one, have been synthesized by reaction of various Schiff bases 2-(4-hydroxyphenylimino)methyl)-4-(aryl)diazenyl)phenol with ethanolic thioglycolic acid. Schiff bases were obtained by the reactions of 4-amino phenol with 2-hydroxy-5-((aryl)diazenyl)benzaldehyde. The structures of the newly synthesized compounds were confirmed by IR,¹H NMR, mass spectra, and C, H, N elemental analysis. The thiazolidinone derivatives were evaluated for their antibacterial and antifungal activity.

Full text of DOI:10.1002/jhet.2620

Month 2016
Synthesis, Characterization, Antibacterial, and Antifungal Activity of
Novel 2-(2-hydroxy-5-((aryl)-diazenyl)phenyl)-3-(4-hydroxyphenyl)-
thiazolidin-4-one
a
b
c
c
*
Himani N. Chopde, Chandrashekhar P. Pandhurnekar, Jyotsna S. Meshram, and Ramakanth Pagadala
aDepartment of Chemistry, G. H. Raisoni Academy of Engineering and Technology, Nagpur, Maharashtra, India
bDepartment of Applied Chemistry, Shri Ramdeobaba College of Engineering and Management,
Nagpur, Maharashtra, India
cDepartment of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, India
*
E-mail: himanichopde@gmail.com
Received December 31, 2015
DOI 10.1002/jhet.2620
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel thiazolidinones, that is, 2-(2-hydroxy-5-((aryl)-diazenyl)phenyl)-3-(4-hydroxyphenyl)-
thiazolidin-4-one, have been synthesized by reaction of various Schiff bases 2-(4-hydroxyphenylimino)
methyl)-4-(aryl)diazenyl)phenol with ethanolic thioglycolic acid. Schiff bases were obtained by the reactions
of 4-amino phenol with 2-hydroxy-5-((aryl)diazenyl)benzaldehyde. The structures of the newly synthesized
compounds were confirmed by IR, 1H NMR, mass spectra, and C, H, N elemental analysis. The
thiazolidinone derivatives were evaluated for their antibacterial and antifungal activity.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
are also used as catalysts, pigments and dyes, intermediates
in organic synthesis, polymer stabilizers, and corrosion
inhibitors [13]. It has been found that the activity of azo
linkage increases on the incorporation of suitable hetero-
cyclic moiety [14].
The last few decades have seen a flurry of research
activities in the synthesis and development of heterocyclic
compounds because of their important biological proper-
ties [1]. Heterocyclic compounds containing small rings
have been under investigation for a long time because of
their important medicinal properties and also contributed
to the society from biological and industrial points of view,
which help to understand life processes. Among these
types of heterocyclic molecules, 4-thiazolidinones have
been shown to have various important biological activities
such as antibacterial [2], antifungal [3], antioxidant [4],
anticancer [5], analgesic [6], anti-inflammatory [7], central
nervous system active agent [8], anticonvulsant [9], anti-
HIV [10], antitubercular [11], and antiviral activities [12].
Schiff’s bases are condensation products of primary
amines with carbonyl compounds gaining importance day
by day in present scenario. Schiff’s bases are the com-
pounds carrying imine or azomethine (–C =N–) functional
group and are found to be a versatile pharmacophore for
design and development of various bioactive compounds.
Schiff’s bases exhibit useful biological activities such
anti-inflammatory, analgesic, antimicrobial, anticonvul-
sant, antitubercular, anticancer, antioxidant, anthelmintic,
antiglycation, and antidepressant activities. Schiff’s bases
The increasing cases of microbial resistance pose a
major concern to the pharmaceutical industries and have
become a threat for human life worldwide. Moreover, inva-
sive microbial infections caused by multi-drug-resistant
Gram-positive and Gram-negative bacteria, fungi, viruses,
and other microbes are difficult to diagnose and treat. They
are the major cause of morbidity and mortality especially in
immune-suppressed and hospital-acquired patients. In such
scenario, a pharmacophore hybrid approach for exploration
of novel and highly active compounds is an effective and
commonly used direction in modern medicinal chemistry.
Hybridization of two different bioactive molecules with
complementary pharmacophoric functions or with different
mechanisms of action often showed synergistic effects
[15,16]. This hypothesis was confirmed by the results of
our previous studies that allowed identification of the
antibacterial and antifungal activity of 4-thiazolidinone
derivatives coupled with other heterocyclic fragments in
one molecule [17]. In continuation of this theme, we have
synthesized new heterocyclic compounds containing
pharmacologically attractive 4-thiazolidinone, azo linkage,
© 2016 Wiley Periodicals, Inc.

H. N. Chopde, C. P. Pandhurnekar, J. S. Meshram, and R. Pagadala
Vol 9999
Scheme 1. Synthetic route of 2-(2-hydroxy-5-((aryl)-diazenyl)phenyl)-3-
(4-hydroxyphenyl)-thiazolidin-4-one (3a–3g).
were recrystallized in chloroform. The yield of the
products obtained within 70%–85%. The structural
elucidation of starting aromatic aldehydes (1e–1g),
Schiff’s bases (2a–2g), and thiazoloidinones (3a–3g) were
done using various spectral and analytical methods such
1
as by IR, H NMR, mass spectral, and C, H, N elemental
analysis. Formation of Schiff’s bases were confirmed with
strong signal at 1650–1690 cm-1 for the –N =C– group in
the compounds 2a–2g, whereas the disappearance of such
peaks and the appearance of IR frequencies at 650–690cmÀ1
for the C-S-C 4-thiazolodinone group and 1610–1690cmÀ1
for the C = O confirms the formation of the thiazolidinone
ring in the newly synthesized compounds. Resultant data
1
obtained from the H-NMR, mass spectra, and elemental
analysis confirmed the structure of these compounds.
In-vitro antibacterial and antifungal activity.
A new
series
2-(2-hydroxy-5-((aryl)-diazenyl)phenyl)-3-(4-
and Schiff’s base moieties (Scheme 1) and undertaken the
systematic study of these new compounds for their potency
as an antibacterial and antifungal agent. Also, these
synthesized compounds were characterized using different
analytical and spectroscopic techniques.
hydroxyphenyl)-thiazolidin-4-one (3a–3g) have been
synthesized and evaluated for their ability to inhibit the
growth of different bacterial strains such as
Staphylococcus aureus, Bacillus subtilis, Pseudomonas
sp., and Escherichia coli, whereas antifungal activity was
checked against the Candida albicans and Aspergillus
niger strains. The antibacterial and antifungal activities of
the compound were evaluated by measuring the zone of
inhibition on nutrient agar plates and Sabouraudı’s agar
plates, respectively. The results were recorded in triplicate
using ampicillin as a standard drug for antibacterial activity
whereas flucanazole as a standard drug for antifungal
activity. The results have been collected in Table 1.
It can be observed from the Table 1 that compounds 3c,
3d, 3f, and 3g have shown good biological activity, whereas
3b and 3e even shown better activity as compared to bioac-
tivity of standard drug against S. aureus. Compounds 3d,
3e, 3f, and 3g posses better bioactivity in comparision with
standard drug against B. subtilis. Compounds 3c, 3d, 3f, and
3g posses good antibacterial activity as compared with
ampicillin against Pseudomonas sp. Gram-negative
RESULTS AND DISCUSSION
General.
An efficient synthesis of series of
thiazolidinones, that is, 2-(2-hydroxy-5-((aryl)-diazenyl)
phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one, has been
done by reaction of various Schiff bases, that is, 2-(4-
hydroxyphenylimino)methyl)-4-(aryl)diazenyl)phenol with
ethanolic thioglycolic acid. Schiff bases were obtained by
the reactions of 4-amino phenol with 2-hydroxy-5-((aryl)
diazenyl)benzaldehyde. The starting compounds, that is,
2-hydroxy-5-((aryl)diazenyl)benzaldehyde, have been
obtained in the similar manner as reported earlier in our
previous papers [18]. Physical properties and characterization
data of compounds 1a, 1b, 1c, and 1d have been provided
in the literatures [18]. The newly obtained crude products
Table 1
Biological activities of 2-(2-hydroxy-5-((aryl)-diazenyl)phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one.
Antibacterial activity
(Zone of inhibition in mm at 500 μg/mL)
Antifungal activity
Compound
S. aureus
B. subtilis
Pseudomonas sp.
E. coli
C. albicans
A. niger
3a
3b
3c
3d
3e
3f
3 g
5.6
9.3
8.7
8.9
10.2
8.4
8.9
9
4.8
5.2
5.8
6.9
6.4
7.0
7.3
6
9.7
14.8
17.9
14.2
15.7
18.2
14.8
16.3
17
10.5
12.4
13.7
12.7
11.8
11.0
10.1
13
11.7
10.4
11.4
11.9
13.4
15.8
14.9
15
11.0
13.8
12.5
11.8
14.0
13.0
12
Standard drug
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DOI 10.1002/jhet

Month 2016
Synthesis, Characterization, Antibacterial, and Antifungal Activity
bacterial stains. Compounds 3b, 3e, 3d, and 3g posses good
to better activity against E. coli bacterial stains. Thus, it can
be concluded that the bacterial activity of the compounds is
due to the presence of the thiazolidinone ring present, and it
also depends up on the group attached to the ring and its po-
sition. When an antifungal study was done, it was observed
that compounds 3b, 3c, and 3d posses good activity against
C. albicans, whereas compounds 3d, 3e, and 3f posses good
activity against A. niger.
Compounds possessing a nitro group on the ring struc-
ture are the most active group against C. albicans, while
the hydroxyphenyl-group possessing derivatives have
good activity against A. niger. Further biological assess-
ment is also warranted to determine additional biological
parameters to have a deeper insight into structure–activity
relationship and to optimize the effectiveness of this series
of molecules. It would have also been interesting to study
bioactivity with a wider range of compounds to establish
the importance of the functional groups.
Characterization of 2-hydroxy-5-(p-tolyloxy-diazenyl)-
benzaldehyde (1e).
Yield, 87.16%; m. p.: 125°C; IR
(KBr) cmÀ1: 1055 (Ar-O-CH3), 1485 (N= N), 1735
(aldehydic C=O), 2855 (aldehydic H-C=), 3455 (Ar-OH);
1H NMR (CDCl3) δ: 2.30 (s, 3H, Ar-CH3), 6.90 (d, 2H,
Ar-CH), 7.10–7.15 (m, 3H, Ar-CH), 7.35 (m, 2H, Ar-CH),
10.40 (s, 1H, Ar-CHO), 11.90 (s, 1H, Ar-OH); elemental
analysis of C14H12N2O3, Calcd. (%): C 65.62, H 4.72, N
10.93; found (%): C 65.60, H 4.80, N 11.05; MS: m/z 258
(M+, 100%).
Characterization of 2-hydroxy-5-(m-tolyloxy-diazenyl)-
benzaldehyde (1f).
Yield, 80.55%; m. p.: 130°C; IR
(KBr) cmÀ1: 1050 (Ar-O-CH3), 1489 (N= N), 1745
(aldehydic C = O), 2860 (aldehydic H-C=), 3460 (Ar-
1
OH); H NMR (CDCl3) δ: 2.35 (s, 3H, Ar-CH3), 6.75–
6.80 (m, 2H, Ar-CH), 7.05 (s, 1H, Ar-CH), 7.15–7.20
(m, 2H, Ar-CH), 7.40–7.45 (m, 2H, Ar-CH), 10.45 (s, 1H,
Ar-CHO), 11.80 (s, 1H, Ar-OH); elemental analysis of
C14H12N2O3, Calcd. (%): C 65.62, H 4.72, N 10.93; found
(%): C 64.90, H 4.70, N 10.00; MS: m/z 257 (M+, 100%).
Characterization of 2-hydroxy-5-(m-tolyloxy-diazenyl)-
benzaldehyde (1g).
Yield, 80.55%; m. p.: 132°C; IR
MATERIALS AND METHODS
(KBr) cmÀ1: 1060 (Ar-O-CH3), 1490 (N= N), 1740
(aldehydic C =O), 2852 (aldehydic H-C=), 3455 (Ar-OH);
1H NMR (CDCl3) δ: 2.10 (s, 3H, Ar-CH3), 6.85–6.95
(m, 3H, Ar-CH), 7.05–7.10 (m, 2H, Ar-CH), 7.40 (t, 2H,
Ar-CH), 10.40 (s, 1H, Ar-CHO), 11.90 (s, 1H, Ar-OH);
elemental analysis of C14H12N2O3, Calcd. (%): C 65.62,
H 4.72, N 10.93; found (%): C 65.50, H 4.75, N 10.80;
MS: m/z 257 (M+, 100%).
All the chemicals and solvents were obtained from
E-Merck, India (AR grade) and were used without further
purification. Melting points were taken in an open capillary
tube. IR spectra were recorded on a Shimadzu Dr-8031
instrument. Elemental analyses were carried out using a
1
Perkin-Elmer, CHN elemental analyzer model 2400. H
NMR spectra of the synthesized compounds were recorded
General procedure of synthesis of 2-(4-hydroxyphenylimino)
methyl)-4-(aryl)diazenyl)phenol (2a–2g). Equimolar amount
of 2-hydroxy-5-((aryl)diazenyl)benzaldehyde (1a–1g)
(0.002mol) and 4-amino phenol (0.002mol) was dissolved
in ethanol (10mL), and the reaction mixture was refluxed
for 3–4h. The completion of the reaction was monitored by
TLC. After the completion of reaction, it was poured in
ice-cold water, and the solid precipitate was separated out.
The solid deposited was separated by filtration. The crude
product obtained was recrystallized from chloroform.
Characterization of 2-(4-hydroxyphenylimino)-methyl)-4-
on
a
Bruker-Avance (300 MHz), Varian-Gemini
(200 MHz) spectrophotometer using CDCl3 solvent and
TMS as the internal standard. EI-MS spectra were deter-
mined on a LCQ ion trap mass spectrometer (Thermo
Fisher, San Jose, CA, USA), equipped with an EI source.
General Procedure for the synthesis of 2-Hydroxy-5-((aryl)
diazenyl)benzaldehyde (1a–1 g).
Aromatic amines
(0.01 mol) was added in conc. HCl (5 mL) and boiled for
10min. The resulting solution was then cooled to 0–5°C
in ice bath. Aqueous sodium nitrite (NaNO2) (0.01mol,
10mL) solution in the cold condition was added in
dropwise manner to this solution. The reaction mixture
was then vigorously stirred. The temperature of the
reaction mixture was maintained within 0–5°C for at least
1 h to obtain diazonium chloride solution. The resulting
diazonium solution was then poured slowly to alkaline
suspension of salicylaldehyde in water (10 mL, 0.01mol)
with continuous stirring, keeping the temperature within
0–5°C. The pH of the reaction mixture was maintained
within 8 to 10 by simultaneous addition of 10% aqueous
sodium hydroxide solution. The resulting reaction
mixture was kept unstirred for overnight. The obtained
solid precipitate was filtered using Whatman filter paper
number 40 and recrystallized using ethanol.
(phenyldiazenyl)-phenol (2a).
Yield: 85%; m. p.: 70°C;
IR (KBr) cmÀ1: 1420 (C = C), 1450 (N = N), 1640
(–C=N–), 2350 (Ar-CH), 3100 (Ar-OH), 3210 (Ar-OH);
1H NMR (CDCl3): δ= 6.80 (d, 2H, Ar-CH), 7.10–7.30
(m, 4H, Ar-CH), 7.60 (t, 2H, Ar-CH), 8.70 (d, 1H,
Ar-CH), 8.80 (d, 2H, Ar-CH), 9.10 (s, 1H, Ar-CH), 9.30
(s, 1H, N =CH), 9.50 (s, 1H, Ar-OH), 11.30 (s, 1H,
Ar-OH); elemental analysis of C19H15N3O2, Calcd. (%):
C 71.91, H 4.76, N 13.24; found (%): C 71.90, H 4.70,
N 13.20; MS: m/z 317.10 (M+, 100%).
Characterization of 2-(4-hydroxyphenylimino)-methyl)-4-(4-
nitrophenyl)-diazenyl)-phenol (2b).
Yield: 80%; m. p.:
85°C; IR (KBr) cmÀ1: 1310 (Ar-NO2), 1440 (C = C),
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H. N. Chopde, C. P. Pandhurnekar, J. S. Meshram, and R. Pagadala
Vol 9999
1470 (N = N), 1670 (–C = N–), 2370 (Ar-CH), 3110
(Ar-OH), 3220 (Ar-OH); 1H NMR (CDCl3): δ= 6.90
(d, 2H, Ar-CH), 7.10–7.20 (m, 3H, Ar-CH), 7.80 (d, 2H,
Ar-CH), 8.30 (q, 2H, Ar-CH), 8.70 (d, 1H, Ar-CH), 9.00
(s, 1H, Ar-CH), 9.20 (s, 1H, N =CH), 9.60 (s, 1H,
Ar-OH), 11.40 (s, 1H, Ar-OH); elemental analysis of
C19H14N4O4, Calcd. (%): C 62.98, H 3.89, N 15.46;
found (%): C 62.90, H 3.80, N 15.40; MS: m/z 362.00
(M+, 100%).
Characterization of 2-(4-hydroxyphenylimino)-methyl)-4-((2-
methoxyphenyl)-diazenyl)phenol (2g). Yield: 68%; m. p.:
91°C; IR (KBr) cmÀ1: 1040 (Ar-O-CH3), 1440 (C = C),
1480 (N= N), 1670 (–C =N–), 2370 (Ar-CH), 3110
(Ar-OH), 3230 (Ar-OH); 1H NMR (CDCl3): δ= 3.90
(s, 3H, O-CH3), 7.15–7.20 (m, 4H, Ar-CH), 7.65 (d, 1H,
Ar-CH), 7.95 (d, 1H, Ar-CH), 8.80 (d, 1H, Ar-CH), 9.10
(s, 1H, Ar-CH), 9.20 (s, 1H, N=CH), 9.45 (s, 1H, Ar-OH),
11.35 (s, 1H, Ar-OH); elemental analysis of C20H17N3O3,
Calcd. (%): C 69.15, H 4.93, N 12.10; found (%):
C 69.25, H 5.00, N 12.20; MS m/z 346.65 (M+, 100%).
General procedure of synthesis of 2-(2-hydroxy-5-((aryl)-
diazenyl)phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one (3a–
Characterization of 2-(4-hydroxyphenylimino)-methyl)-4-(3-
nitrophenyl)-diazenyl)-phenol (2c).
Yield: 75%; m. p.:
82°C; IR (KBr) cmÀ1: 1330 (Ar-NO2), 1430 (C = C),
1480 (N = N), 1650 (–C = N–), 2390 (Ar-CH), 3120
(Ar-OH), 3220 (Ar-OH); 1H NMR (CDCl3): δ= 6.85
(d, 2H, Ar-CH), 7.20–7.25 (m, 3H, Ar-CH), 7.90 (t, 1H,
Ar-CH), 8.40 (q, 1H, Ar-CH), 8.70–8.80 (m, 2H,
Ar-CH), 9.05 (s, 1H, Ar-CH), 9.30 (s, 1H, N= CH), 9.55
(s, 1H, Ar-OH), 11.30 (s, 1H, Ar-OH); elemental analysis
of C19H14N4O4, Calcd. (%): C 62.98, H 3.89, N 15.46;
found (%): C 62.80, H 3.80, N 15.30; MS: m/z 362.10
(M+, 100%).
3g).
Equimolar amount of 2-(4-hydroxyphenylimino)
methyl)-4-(aryl)diazenyl)phenol (2a–2g) (0.002 mol) and
thioglycolic acid (0.002 mol) was dissolved in ethanol
(10 mL), and the reaction mixture was refluxed for
14–16h. The completion of the reaction was monitored
by TLC. After the completion of reaction, it was poured
in ice-cold water, and the solid precipitate was separated
out. Collect the solid deposit by filtration and the crude
product was recrystallized from chloroform.
Characterization of 2-(4-hydroxyphenylimino)-methyl)-4-(2-
nitrophenyl)-diazenyl)-phenol (2d).
Yield: 78%; m. p.:
Characterization of 2-(2-hydroxy-5-((phenyl)-diazenyl)phenyl)-
80°C; IR (KBr) cmÀ1: 1320 (Ar-NO2), 1410 (C = C), 1450
3-(4-hydroxyphenyl)thiazolidin-4-one (3a).
Yield: 70%;
(N =N), 1660 (–C=N–), 2380 (Ar-CH), 3100 (Ar-OH),
3210 (Ar-OH); H NMR (CDCl3): δ= 6.80 (d, 2H, Ar-CH),
m. p.: 110°C; IR (KBr) cmÀ1: 670 (C-S-C, 4-thiazolidinone),
730 (1, 2 disubstituted benzene ring), 1230 (C-N), 1440
(C = C), 1470 (N= N), 1610 (C = O, thiazolidinone), 2370
(Ar-CH), 3110 (Ar-OH), 3220 (Ar-OH); 1H NMR
(CDCl3): δ= 3.95–4.05 (m, 2H, S-CH2-C thiazolidinone
ring); 6.45 (s, 1H, S-CH-N, thiazolidinone ring),
7.10–7.15 (m, 3H, Ar-CH), 7.30–7.35 (m, 3H, Ar-CH),
7.50–7.60 (m, 4H, Ar-CH), 8.20 (d, 2H, Ar-CH), 9.50
(s, 1H, Ar-OH), 9.70 (s, 1H, Ar-OH); elemental analysis
of C21H17N3O3S, Calcd. (%): C 64.43, H 4.38, N 10.73,
S 8.19; found (%): C 64.40, H 4.30, N 10.50, S 8.10;
MS: m/z 391.00 (M+, 100%).
1
7.15–7.30 (m, 3H, Ar-CH), 7.90–8.20 (m, 2H, Ar-CH),
8.30–8.35 (q, 2H, Ar-CH), 8.75 (d, 1H, Ar-CH), 9.10
(s, 1H, Ar-CH), 9.15 (s, 1H, N=CH), 9.45 (s, 1H, Ar-OH),
11.25 (s, 1H, Ar-OH); elemental analysis of C19H14N4O4,
Calcd. (%): C 62.98, H 3.89, N 15.46; found (%):
C 62.80, H 3.70, N 15.40; MS: m/z 362.00 (M+, 100%).
Characterization of 2-(4-hydroxyphenylimino)-methyl)-4-((4-
methoxyphenyl)-diazenyl)phenol (2e). Yield: 84%; m. p.:
95°C; IR (KBr) cmÀ1: 1035 (Ar-O-CH3), 1410 (C = C),
1480 (N= N), 1660 (–C = N–), 2360 (Ar-CH), 3130 (Ar-
1
OH), 3250 (Ar-OH); H NMR (CDCl3): δ =3.83 (s, 3H,
Characterization of 2-(2-hydroxy-5-((4-nitro-phenyl)-diazenyl)
O-CH3), 6.80 (d, 2H, Ar-CH), 7.20–7.25 (m, 5H, Ar-
CH), 7.85 (d, 2H, Ar-CH), 8.70 (d, 1H, Ar-CH), 9.10 (s,
1H, Ar-CH), 9.30 (s, 1H, N= CH), 9.50 (s, 1H, Ar-OH),
11.25 (s, 1H, Ar-OH); elemental analysis of C20H17N3O3,
Calcd. (%): C 69.15, H 4.93, N 12.10; found (%): C
69.45, H 5.05, N 12.05; MS: m/z 349.35 (M+, 100%).
Characterization of 2-(4-hydroxyphenylimino)-methyl)-4-((3-
phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one (3b).
Yield:
75%; m. p.: 120°C; IR (KBr) cmÀ1: 680 (C-S-C, 4-
thiazolidinone), 740 (1, 2 disubstituted benzene ring),
1250 (C-N), 1315 (Ar-NO2), 1420 (C=C), 1460 (N=N),
1630 (C=O, thiazolidinone), 2360 (Ar-CH), 3170 (Ar-
1
OH), 3210 (Ar-OH); H NMR (CDCl3): δ=3.90–4.00 (m,
2H, S-CH2-C thiazolidinone ring), 6.50 (s, 1H, S-CH-N,
thiazolidinone ring), 7.00–7.10 (m, 3H, Ar-CH), 7.35 (d,
2H, Ar-CH), 7.50 (t, 1H, Ar-CH), 7.70 (s, 1H, Ar-CH),
7.90 (d, 2H, Ar-CH), 8.40 (d, 2H, Ar-CH), 9.40 (s, 1H,
Ar-OH), 9.60 (s, 1H, Ar-OH); elemental analysis of
C21H16N4O5S, Calcd. (%) : C 57.79, H 3.70, N 12.84, S
7.35; found (%): C 57.50, H 3.50, N 12.70, S 7.30; MS:
m/z 436.00 (M+, 100%).
methoxyphenyl)-diazenyl)phenol (2f).
Yield: 70%; m. p.:
93° C; IR (KBr) cmÀ1: 1045 (Ar-O-CH3), 1430 (C = C),
1450 (N= N), 1690 (–C = N–), 2380 (Ar-CH), 3120 (Ar-
1
OH), 3260 (Ar-OH); H NMR (CDCl3): δ =3.80 (s, 3H,
O-CH3), 7.15–7.20 (m, 4H, Ar-CH), 7.35 (t, 1H, Ar-CH),
7.55 (d, 2H, Ar-CH), 8.75 (d, 1H, Ar-CH), 9.00 (s, 1H,
Ar-CH), 9.15 (s, 1H, N =CH), 9.45 (s, 1H, Ar-OH),
11.20 (s, 1H, Ar-OH); elemental analysis of C20H17N3O3,
Calcd. (%): C 69.15, H 4.93, N 12.10; found (%): C
68.95, H 4.95, N 12.15; MS: m/z 347.65 (M+, 100%).
Characterization of 2-(2-hydroxy-5-((3-nitrophenyl)-diazenyl)
phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one (3c).
72%; m. p.: 120°C; IR (KBr) cmÀ1: 680 (C-S-C,
Yield:
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DOI 10.1002/jhet

Month 2016
Synthesis, Characterization, Antibacterial, and Antifungal Activity
4-thiazolidinone), 750 (1, 2 disubstituted benzene ring),
1260 (C-N), 1340 (Ar-NO2), 1420 (C=C), 1480 (N=N),
1690 (C=O, thiazolidinone), 2350 (Ar-CH), 3170
9.40 (s, 1H, Ar-OH), 9.75 (s, 1H, Ar-OH), elemental
analysis of C22H19N3O3S, Calcd. (%): C 65.17, H 4.72,
N 10.36, S 7.91; found (%): C 64.90, H 4.50, N 10.10, S
7.50; MS m/z 405.10 (M+, 100%).
1
(Ar-OH), 3280 (Ar-OH); H NMR (CDCl3): δ=3.85–3.90
(q, 2H, S-CH2-C thiazolidinone ring), 6.55 (s, 1H, S-CH-
N, thiazolidinone ring), 7.05 (m, 3H, Ar-CH), 7.30 (d, 2H,
Ar-CH), 7.55 (q, 1H, Ar-CH), 7.75 (d, 1H, Ar-CH),
7.95–8.10 (m, 2H, Ar-CH), 8.20–8.30 (m, 2H, Ar-CH),
9.50 (s, 1H, Ar-OH), 9.75 (s, 1H, Ar-OH); elemental
analysis of C21H16N4O5S, Calcd. (%): C 57.79, H 3.70, N
12.84, S 7.35; found (%): C 57.70, H 3.60, N 12.80, S
7.20; MS: m/z 436.00 (M+, 100%).
Characterization of 2-(2-hydroxy-5-((2-methoxyphenyl)-diazenyl)
phenyl)-3-(4-hydroxy-phenyl)-thiazolidin-4-one (3g). Yield:
65%; m. p.: 115°C; IR (KBr) cmÀ1: 690 (C-S-C,
4-thiazolidinone), 780 (1, 2 disubstituted benzene ring),
1055 (Ar-O-CH3), 1270 (C-N), 1420 (C = C), 1460
(N =N), 1680 (C = O, thiazolidinone), 2390 (Ar-CH),
3150 (Ar-OH), 3290 (Ar-OH); 1H NMR (CDCl3):
δ= 3.80 (s, 3H, O-CH3), 4.85–4.95 (q, 2H, S-CH2-C
thiazolidinone ring), 6.50 (s, 1H, S-CH-N, thiazolidinone
ring), 6.90 (d, 1H, Ar-CH), 6.95–7.05 (m, 3H, Ar-CH),
7.20–7.25 (m, 1H, Ar-CH), 7.45–7.50 (m, 2H, Ar-CH),
7.70 (s, 1H, Ar-CH), 7.95 (d, 1H, Ar-CH), 9.45 (s, 1H,
Ar-OH), 9.70 (s, 1H, Ar-OH); elemental analysis of
C22H19N3O3S, Calcd. (%) : C 65.17, H 4.72, N 10.36, S
7.91; found (%): C 65.00, H 4.60, N 10.20, S 7.60; MS:
m/z 405.00 (M+, 100%).
Characterization of 2-(2-hydroxy-5-((2-nitrophenyl)-diazenyl)
phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one (3d).
Yield:
65%; m. p.: 115°C; IR (KBr) cmÀ1: 660 (C-S-C, 4-
thiazolidinone), 770 (1, 2 disubstituted benzene ring),
1230 (C-N), 1325 (Ar-NO2), 1440 (C=C), 1470 (N=N),
1660 (C=O, thiazolidinone), 2380 (Ar-CH), 3140 (Ar-
1
OH), 3250 (Ar-OH); H NMR (CDCl3): δ=3.95–4.05 (q,
2H, S-CH2-C thiazolidinone ring), 6.50 (s, 1H, S-CH-N,
thiazolidinone ring), 7.00–7.05 (m, 3H, Ar-CH), 7.30 (d,
2H, Ar-CH), 7.50 (q, 1H, Ar-CH), 7.75 (d, 1H, Ar-CH),
7.90–8.05 (m, 2H, Ar-CH), 8.25–8.35 (m, 2H, Ar-CH),
9.40 (s, 1H, Ar-OH), 9.65 (s, 1H, Ar-OH); elemental
analysis of C21H16N4O5S, Calcd. (%): C 57.79, H 3.70, N
12.84, S 7.35; found (%): C 57.60, H 3.40, N 12.60, S
7.10; MS: m/z 436.00 (M+, 100%).
Biological activity. Antibacterial and antifungal activities
were tested for newly synthesized 2-(2-hydroxy-5-((aryl)-
diazenyl)phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one
(3a–3g) using the well diffusion method against the
different Gram-positive and Gram-negative bacterial
stains and fungi stains. Different bacterial stains used for
the screening were S. aureus (Gram-positive), B. subtilis
(Gram-positive), Proteus vulgaris. (Gram-negative) and
E. coli (Gram-negative). Antifungal activities of these
compounds were also tested against C. albicans and A.
niger. The stock solutions of thiazolidinone derivatives or
standard drug in dimethyl sulfoxide (100 μg/mL) were
prepared for the study. The sterilized Petri dishes and
agar medium were used in the present work. The
antibacterial activities of compounds were evaluated by
measuring the zone of inhibition on nutrient agar plate.
Muller Hinton agar was used in the antibacterial study,
whereas Sabouraud’s Dextrose agar was used for the
antifungal activity study. The composition of nutrient
agar medium to culture the bacterial strains used in the
present study was: peptone (10 gm), agar powder (20 gm),
sodium chloride powder (10 gm), beef extract (5 gm), and
distilled water (1000mL). The pH of the nutrient agar
medium was adjusted to 7.2. The nutrient agar medium
was mixed well and was autoclaved at 15lbs pressure at
120°C for at least 15min.
Characterization of 2-(2-hydroxy-5-((4-methoxyphenyl)-diazenyl)
phenyl)-3-(4-hydroxy-phenyl)-thiazolidin-4-one (3e).
Yield:
80%; m. p.: 110°C; IR (KBr) cmÀ1: 650 (C-S-C, 4-
thiazolidinone), 770 (1, 2 disubstituted benzene ring),
1060 (Ar-O-CH3), 1250 (C-N), 1440 (C =C), 1470
(N = N), 1670 (C = O, thiazolidinone), 2340 (Ar-CH),
3130 (Ar-OH), 3260 (Ar-OH); 1H NMR (CDCl3):
δ= 3.80 (s, 3H, O-CH3), 4.00–4.10 (q, 2H, S-CH2-C
thiazolidinone ring), 6.45 (s, 1H, S-CH-N, thiazolidinone
ring), 7.10–7.15 (m, 3H, Ar-CH), 7.25 (d, 2H, Ar-CH),
7.35 (d, 2H, Ar-CH), 7.50 (d, 1H, Ar-CH), 7.80 (s, 1H,
Ar-CH), 8.85 (d, 2H, Ar-CH), 9.55 (s, 1H, Ar-OH), 9.85
(s, 1H, Ar-OH); elemental analysis of C22H19N3O3S,
Calcd. (%): C 65.17, H 4.72, N 10.36, S 7.91; found (%):
C 65.10, H 4.70, N 10.30, S 7.80; MS: m/z 405.00
(M+, 100%).
Characterization of 2-(2-hydroxy-5-((3-methoxyphenyl)-diazenyl)
phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one (3f).
Yield:
70%; m. p.: 125°C; IR (KBr) cmÀ1: 680 (C-S-C,
4-thiazolidinone), 750 (1, 2 disubstituted benzene ring),
1060 (Ar-O-CH3), 1230 (C-N), 1410 (C =C), 1450
(N = N), 1650 (C = O, thiazolidinone), 2380 (Ar-CH),
3170 (Ar-OH), 3250 (Ar-OH); 1H NMR (CDCl3):
δ= 3.90 (s, 3H, O-CH3), 4.05–4.15 (q, 2H, S-CH2-C
thiazolidinone ring), 6.55 (s, 1H, S-CH-N, thiazolidinone
ring), 7.05–7.15 (m, 3H, Ar-CH), 7.15-7.40 (m, 5H,
Ar-CH), 7.50–7.55 (m, 2H, Ar-CH), 7.75 (s, 1H, Ar-CH),
In the sterilized agar medium, 10mL of one day old
bacterial/fungal cultures were added. Bacterial or fungal
culture were inoculated into nutrient broth and incubated
at (37 2)C on rotary shaker at 100rpm. After 36-h incu-
bation, bacterial suspensions were used for further tests.
This media were poured in Petri dishes and allowed to
set. Two wells were created using a 5 mm cork borer. In
this well, 0.1 mL of test samples/standards were filled.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

H. N. Chopde, C. P. Pandhurnekar, J. S. Meshram, and R. Pagadala
Vol 9999
[4] (a) Abdul-Kader Saleh, N.; El-Abd Saltani, H.; Abbas Al-Issa,
F.; Abul-kasem Errabie, A.; Gomaa Melad, A. S. J Chin Chem Soc 2013,
60, 1353; (b) Campos, J. C.; Gouvêa, D. P.; Ribeiro, C. d. S.; Dutra, F. S.
P.; Stefanello, F. M.; Pereira, C. M. P.; Cunico, W.; Siqueira, G. M. J
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Bednarczyk-Cwynar, B.; Vasylenko, O.; Kazakova, O.; Zimenkovsky, B.;
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All the nutrient agar plates were incubated at 37 C for 24 h
in antibacterial study and at 37 C for 48 h in antifungal
activity study. The plates were observed for clear zone of
inhibition. Then, diameters of the zone of inhibition for
these compounds were measured. The biological activities
were tested for at least three times for all the compounds
against all microorganisms, and the average value has been
reported in Table 1.
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CONCLUSION
In the present research work, we have synthesized series
of thiazolidinones, that is, 2-(2-hydroxy-5-((aryl)-diazenyl)
phenyl)-3-(4-hydroxyphenyl)-thiazolidin-4-one, by reac-
tion of various Schiff bases 2-(4-hydroxyphenylimino)
methyl)-4-(aryl)diazenyl)phenol with ethanolic thioglycolic
acid in good yields. Schiff bases were obtained by the reac-
tions of 4-amino phenol with 2-hydroxy-5-((aryl)diazenyl)
benzaldehyde. The structure of the newly synthesized
compounds was confirmed by IR, 1H NMR, mass spectral,
and C, H, N elemental analysis. The thiazolidinone deriva-
tives were evaluated for their antibacterial and antifungal
activities by well diffusion method in triplicate. These
compounds have shown promising biological activities
against Gram-positive and Gram-negative bacterial stains.
Also, antifungal activities have also been shown of these
compounds. These compounds could be useful as templates
for further development through modification to design
more potent antimicrobial and antifungal agents.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet