Synthesis and biological activity of 3-[4H-(1,2,4)-triazolyl]-2-aryl-1,3- thiazolidin-4-ones

Article abstract of DOI:10.1080/10426500801963772

4-Amino-1,2,4-triazole (1) undergoes facile condensation with aromatic aldehydes to afford the corresponding 4-(arylidene-amino)-4H-[1,2,4]-triazole (2 a-h) in good yields. Cyclocondensation of compounds (2 a-h) with thioglycolic acid yields 3-[4H-(1,2,4)

Full text of DOI:10.1080/10426500801963772

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Synthesis and Biological
Activity of 3-[4H-(1,2,4)-
triazolyl]-2-aryl-1,3-
thiazolidin-4-ones
H. S. Patel a & K. B. Patel a
a Department of Chemistry , Sardar Patel
University , Vallabh Vidyanagar, India
Published online: 26 Sep 2008.
To cite this article: H. S. Patel & K. B. Patel (2008) Synthesis and Biological
Activity of 3-[4H-(1,2,4)-triazolyl]-2-aryl-1,3-thiazolidin-4-ones, Phosphorus,
Sulfur, and Silicon and the Related Elements, 183:10, 2391-2398, DOI:
10.1080/10426500801963772
To link to this article: http://dx.doi.org/10.1080/10426500801963772
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Phosphorus, Sulfur, and Silicon, 183:2391–2398, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801963772
Synthesis and Biological Activity of
3-[4H-(1,2,4)-triazolyl]-2-aryl-1,3-thiazolidin-4-ones
H. S. Patel and K. B. Patel
Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar,
India
4-Amino-1,2,4-triazole (1) undergoes facile condensation with aromatic aldehydes
to afford the corresponding 4-(arylidene-amino)-4H-[1,2,4]-triazole (2 a−h) in good
yields. Cyclocondensation of compounds (2 a−h) with thioglycolic acid yields 3-[4H-
(1,2,4)-triazolyl]-2-aryl-1,3-thiazolidin-4-ones (3 a−h). The structures of these com-
pounds were established on the basis of analytical and spectral data. The newly syn-
thesized compounds were evaluated for their antibacterial and antifungal activities.
Keywords 4-Amino-1,2,4-triazole; antibacterial activity; thiazolidinone
INTRODUCTION
4-Amino-1,2,4-triazoles and their condensed products1−3 are the start-
ing materials for the synthesis of a wide variety of heterocyclic deriva-
tives, which are of great importance in medicinal chemistry.4−6 Many
reports of the synthesis of N-arylideneamino-1,2,4-triazole deriva-
tives are currently known.7−9 These compounds display diverse bio-
logical activity, including antibacterial, antifungicidal, analgesic, anti-
inflammatory activity.10−12 These heterocyclic systems find wide use
in medicine, agriculture, and industry. 4-thiazolidinones13−15 give good
pharmacological properties.16 4-thiazolidinones are known to exhibit
antitubercular,17 antibacterial,18 antifungal,19 and anticonvulsant ac-
tivities; therefore, we wanted to determine if merging thiazolidinone
and triazole moieties would enhance the drug activity of these com-
pounds to some extent, or whether they might possess some of the
abovementioned biological activities. From this point of view, the
objective of the present work is to prepare new derivatives of triazole
Received 17 July 2007; accepted 20 December 2007.
The authors are thankful to Dr. J. S. Parmar, Head, Department of Chemistry, for
providing laboratory facilities.
Address correspondence to H. S. Patel, Department of Chemistry, Sardar Patel Uni-
versity, Vallabh Vidyanagar 388 120, India. E-mail: hsp13152@rediffmail.co.in
2391

2392
H. S. Patel and K. B. Patel
N
N
N
NH2
(1)
i) RCHO
ii) EtOH/Conc.
H2SO4
H
N
N
N
R
C
N
(2 a-h)
i)
SHCH2COOH
ii)
ANH.
ZnCl2 / DMF
H
N
N
C
S
R
N
C
N
O
(3 a-h)
Where, R = (a) C6H5
(b) 4-OH-C6H4
(e) 4-OH-3-OCH3-C6H3
(f) 4-Cl-C6H4
(c) 2-OH-C6H4
(g) 2-NO2-C6H4
(d) 4-OCH3-C6H4 (h) 5-Br-2-OH-C6H3
SCHEME 1
containing thiazolidinone moiety. Hence, the present communica-
tion comprises the synthesis of 3-[4H-(1,2,4)-triazolyl]-2-aryl-1,3-
thiazolidin-4-ones. The reaction is shown in Scheme 1, and the charac-
terization is shown in Tables II and III.
BIOLOGICAL SCREENING
Antibacterial Activities
Antibacterial activities of all the compounds were studied against
gram-positive bacteria (Bacillus subtilis and staphylococcus aureus)

2393

2394

Triazolyl Thiazolidinones
2395
TABLE III Antibacterial Activity of Compounds (3a–h)
Zone of inhibition
Gram +ve
Staphylococcus
Gram –ve
Bacillus
subtilis
Klebsiella
promioe
Salmonella
typhi
Compounds
aureus
E. coli
3a
3b
3c
3d
3e
3f
3g
3h
55
43
45
72
64
81
83
68
83
56
65
65
78
60
72
70
56
57
48
57
70
75
42
70
68
62
72
45
54
42
82
63
85
78
66
80
65
69
84
86
40
68
75
58
75
Tetracycline
and gram-negative bacteria (E.coli, salmonella typhi, and klebsiella
promioe) at a concentration of 50 µg/ml by agar cup plate method.
Methanol system was used as control in this method. Under similar
conditions, using tetracycline as a standard for comparison, we carried
out a control experiment. The area of inhibition of zone measured in
cm. Compound 3d, 3f, and 3g were found more active against the above
microbes. Other compounds found to be less or moderate active than
tetracycline (Table III).
Antifungal Activities
The fungicidal activity of all the compounds was studied at 1000 ppm
concentration in vitro. Plant pathogenic organisms used were penicil-
lium expansum, Botrydepladia thiobromine, Nigrospora Sp., Trichoth-
esium Sp., and Rhizopus nigricum. The antifungal activity of all the
compounds (3a−h) was measured on each of these plant pathogenic
strains on a potato dextrose agar (PDA) medium. Such a PDA medium
contained potato 200 g, dextrose 20 g, agar 20 g and 1 L water. Five
day old cultures were employed. The compounds to be tested were sus-
pended (1000 ppm) in a PDA medium and autoclaved at 120◦C for
15 min at 15 atm pressure; the resulting product was poured into ster-
ile Petri plates, and the organisms were inoculated after cooling the
Petri plates. The percentage inhibition for fungi was calculated after
five days using the formula given below:
Percentage of inhibition = 100(X − Y)/X,
(1)

2396
H. S. Patel and K. B. Patel
where, X = area of colony in control plate; and Y = Area of colony in
test plate.
The fungicidal activity displayed by various compounds (3a−h) is
shown in Table IV.
RESULTS AND DISCUSSION
The structures of 4-(arylidene-amino)-4H-[1,2,4]-triazole (2a−h) were
confirmed by elemental analysis and IR spectra showing absorp-
tion band at 1620−1640 cm−1(C N), ∼1040 cm−1(N N of triazole),
3250−3300 cm−1 (C H of Triazole), 3030−3080 cm−1 (C H of Ar.),
1475–1525 cm−1 (C C of Ar.), 1575–1625 cm−1 (C C of Ar.), while
additional peak appears due to substitution in the Aromatic ring show-
ing absorption band at ∼1230 cm−1 (C O), 3450−3550 cm−1 (O H),
2815–2850 cm−1 (C H of OCH3), ∼1095 cm−1 (C Cl), 1310–1360 and
1490–1560 cm−1 ( NO2), ∼1075 cm−1 (C Br). All the spectra com-
prises the common signals with their assignment are : t 9.5–10.2 (2H of
CH=N of triazole and 1H of CH N of arylidene), m 7.5–7.8 (aromatic
proton). The additional signal appears due to substitution in aromatic
ring showing common signals at 5.1–5.3 (H of −OH) and 3.7−3.9 (H of
–OCH3) both as singlets.
The structures assigned to 3-[4H-(1,2,4)-triazolyl]-2-aryl-1,3-
thiazolidin-4-ones (3a−h) were supported by the elemental analysis
and IR spectra showing same absorption bands as in (2a−h) with ad-
ditional bands at 1000−1400 cm−1 (C N of thiazolidinone ring), 1690
cm−1 (C=O of thiazolidinone ring), 680 cm−1 (C S C of thiazolidinone
ring), 3075−3095 cm−1 (=CH2 of thiazolidinone ring). All the com-
pounds show the NMR signals for different kinds of protons at their
respective positions which are same as in (2a−h) with additional sig-
nals with their assignment are: s 3.27−4.18 (CH2 of thiazolidinone
ring) and s 5.80−5.92 (C2-H of thiazolidinone ring), which confirmed
the structures of thiazolidinone derivatives.
The examination of the data reveals that the elemental contents are
consistent with the predicted structure shown in Scheme 1. The IR and
NMR data also allow a direct assignment of the predicted structure.
The final structure of all compounds is confirmed by LC-MS data of
selected samples. The LC-MS of samples 3a and 3c gave the molecular
ion peaks (m/z) at 248 and 265, respectively. These values correspond
to their molecular weight.
The antibacterial activity of series (3a−h) was carried out against
some strains of bacteria. The results show that the prepared compounds
are toxic against the bacteria. The comparison of the antibacterial

Triazolyl Thiazolidinones
2397
TABLE IV Antifungal Activity of Compounds (3a–h)
Zone of inhibition at 1000 ppm (%)
Penicillium Botrydepladia Nigrospora Trichothesium Rhizopus
Compounds
expansum
thiobromine
sp.
sp.
nigricum
3a
3b
3c
3d
3e
3f
75
64
74
70
55
53
62
75
60
71
73
68
58
64
73
80
72
64
78
65
73
63
66
64
55
56
68
80
65
74
62
73
53
70
66
72
68
62
57
69
3g
3h
activity of these compounds with tetracycline shows that these com-
pounds have almost similar activity.
CONCLUSION
The clubbing of 1,2,4-triazole and thiazolidinone has been done success-
fully into one molecule. Both the moieties have important applications
in medicinal use; the produced compounds may be act as good biological
compounds.
EXPERIMENTAL
Melting points were determined in open capillary tubes and are un-
corrected. The IR spectra were recorded in KBr pellets on a Nicolet
1
400D spectrometer and H NMR and spectra were recorded in DMSO
with TMS as internal standard on a Bruker spectrometer at 400 MHz.
LC-MS of selected samples taken on LC-MSD-Trap-SL 01046.
Preparation of 4-(Arylidene-amino)-4H-[1,2,4]-triazole
(2 a−h)—General Procedure
An equimolecular mixture of 4-Amino-1,2,4-triazole 1, (0.84 g, 0.01
mol), and the aromatic aldehyde (a−h) in ethanol(15 ml) and conc.
H2SO4(0.4 ml) was refluxed on a water bath for 1−2 h. The solid sepa-
rated was collected by filtration, dried, and recrystallized from ethanol.
The yields, melting points, and other characterization data of these
compounds are given in Table I.

2398
H. S. Patel and K. B. Patel
Preparation of 3-[4H-(1,2,4)-triazolyl]-2-aryl-1,3-thiazolidin-4-
ones (3 a−h)—General Procedure
A mixture of 4-(arylidene-amino)-4H-[1,2,4]-triazole (2 a h) (0.01 mol)
in DMF (10 ml) and thioglycolic acid (0.87 ml, 0.0125 mol) with a pinch
of anhydrous zinc chloride was refluxed for about 8−9 h. The excess sol-
vent was removed under vacuum and residue was poured into ice-cold
water and then neutralized with sodium bicarbonate solution. Solid
separated was filtered and dried. The product thus obtained was puri-
fied by column chromatography over silica gel using benzene: chloro-
form (8:2 V/V) mixture as eluent. The eluate was concentrated and the
product crystallized from alcohol (50−60 yield%).
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