Synthesis and biological activity of some novel 4-(5-mercapto-1,3,4-thiadiazol-2-yl)-2-phenyl-5-[2-phenylvinyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Article abstract of DOI:10.1155/2010/190179

A novel and efficient route have been designed for the synthesis of 4-(5-mercapto-1,3,4-thiadiazol-2-yl)-2-phenyl-5-[2-phenylvinyl]-2,4-dihydro-3H-1,2,4-triazol-3-one. All the synthesized compound were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR and mass spectra. All the synthesized products were evaluated for their antibacterial activity against B. Subtilis and E.Coli and antifungal activity against A. niger and C.Albican respectively. The results indicate that the present compounds may serve as better fungicides when compared to bactericides. The synthesized compounds have turned to be wonder by possessing antimicrobial properties.

Full text of DOI:10.1155/2010/190179

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2010, 7(2), 545-550
http://www.e-journals.net
Synthesis and Biological Activity of Some Novel
4-(5-Mercapto-1,3,4-thiadiazol-2-yl)-2-phenyl-5-
[2-phenylvinyl]-2,4-dihydro-3H-1,2,4-triazol-3-one
KUMAR SANJEEV S. LAMANI and OBLENNAVAR KOTRESH*
Department of Chemistry,
Karnataka Unversity’s Karnatak Science College,
Dharwad-580001, Karnataka, India.
orgkotresh_org@rediff.com
Received 28 July 2009; Accepted 20 September 2009
Abstract: A novel and efficient route have been designed for the synthesis of
4-(5-mercapto-1,3,4-thiadiazol-2-yl)-2-phenyl-5-[2-phenylvinyl]-2,4-dihydro-
3H-1,2,4-triazol-3-one. All the synthesized compound were characterized by
elemental analysis, IR, 1H NMR, 13C NMR and mass spectra. All the
synthesized products were evaluated for their antibacterial activity against B.
Subtilis and E.Coli and antifungal activity against A. niger and C.Albican
respectively. The results indicate that the present compounds may serve as
better fungicides when compared to bactericides. The synthesized compounds
have turned to be wonder by possessing antimicrobial properties.
Keywords: Sydnone, 1,3,4-Thiadiazole, Triazole, Antimicrobial activity.
Introduction
The therapeutic effects of 1,2,4-triazole and 1,2,4-triazol-3-one containing compounds have
been well studied for a number of pathological conditions including inflammation, cancer,
pain, tuberculosis or hypertension1-9. In addition, it was reported that 1,3,4-thiadiazoles
exhibit various biological activities possibly due to the presence of the C=N-C-S moiety10.
Moreover, synthesis of triazoles fused to another heterocyclic ring has attracted wide spread
attention due to their diverse applications as antibacterial, antidepressant, antiviral,
antitumorial and anti-inflammatory agents, pesticides, herbicides dyes, lubricant and
analytical reagents11. Among these, the commonly known systems are generally triazoles
fused to pyridines, pyridazines, pyrimidines, pyrazines and triazines. Although there are not
many triazoles fused to thiadiazines or thiadiazoles, a number of them are incorporated into

546
O. KOTRESH et al.
a wide variety of therapeutically important compounds possessing a broad spectrum of
biological activities12-15. In this connection, some biheterocyclic compounds containing two
1,2,4-triazol-3-one rings or both 1,2,4-triazol-3-one and 1,3,4-thiadiazole rings have been
synthesized in our laboratory as antimicrobial compounds16.
Sydnones are a novel class of meso-ionic compounds with unique chemical and
physical properties. A vast array of sydnone derivatives have been found to show varied
biological properties17, antioxidant activity18 and liquid crystalline properties19.
Furthermore, sydnones have been used as precursors in 1,3-dipolar additions,20 material
chemistry21 and in battery applications22. In continuation of our effort to develop benign
synthetic methods for sydnone and oxadiazolines23 we report here a new series of 4-(5-
mercapto-1,3,4-thiadiazol-2-yl)-2-phenyl-5-[(E)-2-phenylvinyl]-2,4-dihydro-3H-1,2,4-
triazol-3-one containing 1,3,4-thiadiazole rings. It was interesting to study the
influencing biological behaviors with various substituted oxadiazoles. Therefore, we felt
it of interest to study the chemical reactivity of these heterocyclic 1,3,4-thiadiazole
moieties.
Experimental
Melting points were determined in one end open capillary tubes on a Buchi 530 melting
point apparatus and are uncorrected. Infrared (IR) spectra were recorded for the compounds
on Perkin Elmer Spectrum RXI Spectrophotometer in KBr. 13C nuclear magnetic resonance
1
(13C NMR) and H nuclear magnetic resonance (1H NMR) spectra were recorded for the
compounds on Advance bruker (300 MHz) instrument. Chemical shifts are reported in parts
per million (ppm) using tetramethylsilane (TMS) as an internal standard. All the new
compounds have given CHN analysis within 0.4% of the theoretical values. The purity of
the compounds was confirmed by thin layer chromatography using silica gel glass plates and
a solvent system of benzene:ethanol (8:2). The spots were developed in iodine chamber and
visualized under ultra violet lamp.
All the chemicals purchased were of analytical reagent grade, and were used without
further purification stated is confirmed by measuring M.P. Synthesis of 3-aryl sydnones,
oxadiazolines and triazoles derivatives by slight modification in our reported literature
methods23.
General procedure for compounds 2a-2h (Scheme 1)
To the 5-methyl-3-phenyl-1,3,4-oxadiazol-2(3H)-one (0.01 M) (1), 5-amino-1,3,4-
thiadiazole-2-thiol (0.01 M) in glacial acetic acid (GAA) was added and refluxed for 4 h.
Obtained reaction mixture was poured into crushed ice and left overnight. The solid which
separated out was filtered, washed thoroughly with cold distilled water, dried and
recrystallised from hot ethanol. The other derivatives are also synthesized by same method.
The yield, melting point and other physical properties of synthesized compound are recorded
in Table 1.
General procedure for compounds 3a-3h (Scheme 1)
The title compounds were synthesized by following the procedure: Solution of 2 (0.01 M)
and opportune benzaldehyde (0.01 M) were reacted with glacial acetic acid (10 mL) and
refluxed for 12 h. The solid 4 which separated out was filtered with suction and
recrystallised from dimethylformamide to give pure compound. The physical data of the
compound 3 are given in Table 2. The IR spectra, 13C NMR spectra and 1H NMR spectra of
the title compounds are as follows:

Synthesis and Biological Activity
547
N
N
O
O
SH
N
N
S
O
H2N
CH3
SH
N
S
N
N
in GAA
N
N
R
R
CH3
2
1
Reflux
12 hrs
ArCHO
in GAA
N
S
N
O
SH
N
N
N
R
Ar
3
Scheme 1
Table 1
2d
S. No.
R
Mol weight 291.35 335.36 363.41
2a
2b
2c
2e
2f
2g 2h
m-Cl p-OCH3
349.38 333.38 325.79 325.79 321.37
H
COOH COOC2H5 COOCH3 COCH3 p-Cl
All the products gave satisfactory NMR, IR and MS data Isolated yield.
Table 2. Elemental Analysis of the compounds.
Yield,
%
Elemental analysis
Found (Calc), %
S. No.
R
Meting Point
0 C
Molecular
formula
C
56.98
H
3.46
N S
18.47 16.92
3a
3b
3c
3d
3e
3f
H
197-98
200-01
211-12
232-33
256-57
223-24
194-95
211-12
89
87
72
68
76
C18H13N5OS2
C19H13N5O3S2
C21H17N5O3S2
C20H15N5O3S2
C20H15N5O2S2
(56.97) (3.45) (18.46) (16.90)
53.90 3.10 16.55 15.16
(53.89) (3.09) (16.54) (15.14)
55.87 3.80 15.52 14.21
(55.86) (3.79) (15.51) (14.20)
54.93 3.47 16.02 14.67
(54.91) (3.46) (16.01) (14.66)
56.98 3.60 16.63 15.22
(56.99) (3.59) (16.62) (15.21)
52.24 2.93 16.93 15.48
(52.23) (2.92) (16.92) (15.49)
52.24 2.93 16.93 15.48
(52.23) (2.92) (16.92) (15.49)
55.72 3.70 17.11 15.65
(55.73) (3.69) (17.10) (15.66)
COOH
COOC2H5
COOCH3
COCH3
p-Cl
79 C18H12ClN5OS2
82 C18H12ClN5OS2
3g
3h
m-Cl
p-OCH3
80
C19H15N5O2S2

548
O. KOTRESH et al.
4-(5-Mercapto-1,3,4-thiadiazol-2-yl)-5-methyl-2-phenyl-2,4-dihydro-3H-1,2,4-
triazol-3-one (3a)
IR (cm -1): 1693 (C=O), 1650 (C=C) Alkene, 1530 (C=N), 1317 (CN), 688 (CS); 13C NMR
(300 MHz, δ): 118.7, 121.6, 124.4, 126.4, 128.0, 128.7, 129.0, 135.2, 137.8, 139.0, 152.0,
1
155.0, 184.0; H NMR (300 MHz, δ): 5.16 (d, 1H, olefinic CH), 6.6-7.92 (a set of signals,
12 aromatic protons and olefinic CH).
4-{4-(5-Mercapto-1,3,4-thiadiazol-2-yl)-5-oxo-3-[(E)-2-phenylvinyl]-4,5-dihydro-
1H-1,2,4-triazol-1-yl}benzoic acid (3b)
IR (cm -1): 1700 (C=O), 1611 (C=C) Alkene, 1520 (C=N), 1313 (CN), 675 (CS); 13C NMR
(300 MHz, δ): 118.6, 121.5, 125.9, 126.3, 128.1, 128.6, 130.5, 135.2, 139.1, 143.0, 152.2,
1
155.1, 169.4, 184.2; H NMR (300 MHz, δ): 3.73 (s, 3H, CH3), 5.74 (d, 1H, olefinic CH),
6.83-8.00 (a set of signals, 12H, aromatic protons and olefinic CH).
Ethyl 4-{4-(5-mercapto-1,3,4-thiadiazol-2-yl)-5-oxo-3-[(E)-2-phenylvinyl]-4,5-dihydro-
1H-1,2,4-triazol-1-yl}benzoate (3c)
IR (cm -1): 1691 (C=O), 1640 (C=C) Alkene, 1530 (C=N), 1275 (CN), 773 (CS); 13C NMR
(300 MHz, δ): 3c.14.1, 60.9, 118.5, 121.7, 125.8, 126.5, 128.1, 128.5, 130.1, 135.3, 139.2,
1
142.1, 152.0, 155.2, 166.0, 184.1; H NMR (300 MHz, δ): 2.35 (s, 3H, CH3), 5.84 (d, 1H,
olefinic CH), 6.12-7.85 (a set of signals, 12H, aromatic protons and olefinic CH).
Methyl 4-{4-(5-mercapto-1,3,4-thiadiazol-2-yl)-5-oxo-3-[(E)-2-phenylvinyl]-4,5-dihydro-
1H-1,2,4-triazol-1-yl}benzoate (3d)
IR (cm -1): 1700 (C=O), 1668 (C=C) Alkene, 1591 (C=N), 1326 (CN), 752 (CS); 13C NMR
(δ): 51.5, 118.7, 121.5, 125.5, 126.4, 128.0, 128.7, 130.3, 135.2, 139.0, 142.2, 152.1, 155.3,
166.0, 184.0; 1H NMR (300 MHz, δ): 5.52 (d, 1H, olefinic CH), 6.80-7.48 (a set of signals,
13H, aromatic protons and olefinic CH).
2-(4-Acetylphenyl)-4-(5-mercapto-1,3,4-thiadiazol-2-yl)-5-[(E)-2-phenylvinyl]-2,4-
dihydro-3H-1,2,4-triazol-3-one (3e)
IR (cm-1): 1700 (C=O), 1614 (C=C) Alkene, 1555 (C=N), 1326 (CN), 760 (CS); 13C NMR:
(δ) 29.3, 118.6, 121.4, 126.3, 128.1, 128.6, 129.0, 132.4, 135.1, 139.1, 142.3, 152.0, 155.1,
184.2, 199.8; 1H NMR (300 MHz, δ): 5.12 (d, 1H, olefinic CH), 6.41-7.49 (a set of signals,
13H, aromatic protons and olefinic CH).
2-(4-Chlorophenyl)-4-(5-mercapto-1,3,4-thiadiazol-2-yl)-5-[(E)-2-phenylvinyl]-2,
4-dihydro-3H-1,2,4-triazol-3-one (3f)
IR (cm -1): 1737 (C=O), 1610 (C=C) Alkene, 1532 (C=N), 1269 (CN), 733 (CS); 13C NMR:
(δ) 118.7, 123.0, 126.4, 128.0, 128.7, 129.1, 129.9, 135.2, 135.9, 152.0, 155.0, 139.0, 184.0;
1H NMR: (300 MHz, δ) 5.60 (d, 1H, olefinic CH), 6.99 (d, 2H, olefinic CH), 6.78-8.01 (a
set of signals, 14H, aromatic protons and olefinic CH).
2-(3-Chlorophenyl)-4-(5-mercapto-1,3,4-thiadiazol-2-yl)-5-[(E)-2-phenylvinyl]-2,
4-dihydro-3H-1,2,4-triazol-3-one (3g)
-1
IR (cm ) 1700 (C=O), 1620 (C=C) Alkene, 1542 (C=N), 1274 (CN), 740 (CS); 13CNMR
(δ): 118.8, 119.7, 122.0, 124.5, 126.2, 128.1, 128.6, 130.4, 134.5, 135.3, 139.0, 139.2, 152.1,
1
155.3, 184.2; H NMR (300 MHz, δ): 3.84 (s, 3H, CH3), 5.82 (d, 1H, olefinic CH),
6.72-7.94 (a set of signals, 13H, aromatic protons and olefinic CH).

Synthesis and Biological Activity
549
4-(5-Mercapto-1,3,4-thiadiazol-2-yl)-2-(4-methoxyphenyl)-5-[(E)-2-phenylvinyl]-
2,4-dihydro-3H-1,2,4-triazol-3-one (3h)
IR (cm -1): 1739 (C=O), 1642 (C=C) Alkene, 1542 (C=N), 1334 (CN), 759 (CS); 13C NMR
(δ): 55.9, 114.5, 118.7, 122.6, 126.5, 128.1, 128.8, 130.0, 135.2, 139.1, 152.0, 155.0, 156.3,
1
184.0; H NMR (300 MHz, δ): 3.63 (s, 3H, CH3), 3.72 (s, 3H, CH3), 5.76 (d, 1H, olefinic
CH), 6.60-7.86 (a set of signals, 12H, aromatic protons and olefinic CH).
Biological activity
All the newly synthesized compounds were screened for their antimicrobial activity by cup
plate method at 100 µg/mL concentration in DMF against the Bacterial strains viz., E. coli &
B. subtilis and also against fungal strains viz., A niger and A. sereus. Norfloxacin for bacteria
and griseofulvin as the reference drugs respectively. Some these compounds were less active
against the bacterial strains, but some of them showed selective fungal inhibitory activity.
The antimicrobial data of synthesized compounds are given in Table 3.
Table 3. Anti-microbial activities of compounds.
Antibacterial
Antifungal
B. subtilis A. niger C. Albicans
S. No.
E.coli
16
15
15
12
20
21
15
23
24
--
3a
3b
18
17
14
11
23
22
14
24
24
--
16
19
14
22
20
22
19
20
--
17
20
18
21
21
23
18
21
--
3c
3d
3e
3f
3g
3h
Norf
Gris
DMF
26
04
26
04
04
04
Results and Discussion
The synthesized compounds were characterized by various spectral studies. Some of
compounds (3e, 3f and 3h) were found to be more susceptible towards the fungal strains as
well as bacterial strains. (Figure 1 & 2)
30
25
20
15
10
5
25
20
15
10
5
0
E
E
.
.
c
c
o
o
lili
A. niger
A. niger
3a
3c
3e
3g
0
B. subtilis
B. subtilis
C.Albicans
C. Albicans
Gris
3a
3c
3e
3g
Norf
Figure 1. Antibacterial activity of synthesized
compounds.
Figure 2. Antifungal activity of synthesized
compounds.

550
O. KOTRESH et al.
Acknowledgments
The authors thank the University Sophisticated Instrumentation Centre, Karnatak University,
Dharwad for IR and NMR facilities. Authors are also thankful to Dr. Gireesh Babu K,
BioGenics, Hubli, Karnataka for his kind cooperation and useful suggestions in carrying out
the microbial activities.
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