Synthesis of novel 2-(3′-aryl-sydnon-4′-ylidene)-5′- substituted-[1,3,4]-thiadiazolylamines and [1,3,4]-thiadiazol-2′-yl-3-oxo- [1,2,4]-triazoles as antimicrobial agents

Article abstract of DOI:10.1007/s00044-011-9596-2

The title compounds (3g-n) and (6g-n) were synthesized using 3-arylsydnones as synthons, and the structures were confirmed by IR, ¹H NMR, FAB mass and CHN analysis. These compounds were evaluated for their antibacterial and the antifungal activ

Full text of DOI:10.1007/s00044-011-9596-2

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:867–873
DOI 10.1007/s00044-011-9596-2
ORIGINAL RESEARCH
Synthesis of novel 2-(30-aryl-sydnon-40-ylidene)-50-substituted-
[1,3,4]-thiadiazolylamines and [1,3,4]-thiadiazol-20-yl-3-oxo-
[1,2,4]-triazoles as antimicrobial agents
•
Soujanya Bansode Ravindra Kamble
Received: 28 June 2010 / Accepted: 1 February 2011 / Published online: 17 February 2011
Ó Springer Science+Business Media, LLC 2011
Abstract The title compounds (3g–n) and (6g–n) were
synthesized using 3-arylsydnones as synthons, and the
undergoing addition reactions with different dipolarophiles
(Angadiyavar and George, 1971). The 1,3-dipolar nature of
sydnone in cycloaddition reactions to form five membered
nitrogen and oxygen containing heterocycles has been the
focus of the considerable attention. Our interest in the
chemistry of sydnones including their use as synthons, and
limited reports as source of 1,3-dipoles prompted us to
investigate formation of bi heterocycles (Kamble and
Sudha, 2006; Kamble et al., 2007). In the present study,
we have utilized 1,3-dipolar cycloaddition reaction of the
N-arylsydnone for the formation of 1,3,4-oxadiazole which
intern was used for the formation of the title compounds. In
the past few years, pivotal number of 1,2,4-triazoles (Bing
et al., 2003; Chadha et al., 1998; Gokce et al., 2001 Holla
et al., 2001; Hui et al., 2005; Marina et al., 2002; Sakata
et al., 2000; Varvaresou et al., 2000) and schiff bases have
been studied extensively for their broad spectrum activities
such as fungicidal, herbicidal anticonvulsant, plant growth
regulatory activities, anti-inflammatory, analgesic, anthel-
minthic, anti-tubercular, anti-cancer and antipyretic activ-
ities (Baluja et al., 2006; Pandeya et al., 1999; Patai 1970;
Jungreis and Thabet, 1969).
1
structures were confirmed by IR, H NMR, FAB mass and
CHN analysis. These compounds were evaluated for their
antibacterial and the antifungal activities in terms of mini-
mum inhibitory concentrations (MICs) against the bacterial
strains E. coli, B. cereus, and the fungal strains A. niger,
C. albicans. Some of the compounds have shown significant
activities.
Keywords Sydnone ꢀ 1,3-dipolar cycloaddition ꢀ
1,3,4-thiadiazole ꢀ 1,2,4-triazole ꢀ MIC
Introduction
Essential components in drug designing programme and
search for new leads is the synthesis of molecules, which
are novel yet resemble biologically active molecules by
virtue of presence of critical structural features. Hetero-
cyclic molecules act as functionalised scaffolds and are
known pharmacophores of a number of biologically active
and medicinally useful molecules (Silverman, 1992;
Thompson and Ellman, 1996). Sydnones form a class of
meso-ionic compounds which contain the azomethine
system as a part of an aromatic ring. Due to their aromatic
nature, they undergo electrophilic substitution at 4th posi-
tion and also behave as potential 1,3-dipolar systems,
On the other hand, 1,3,4-thiadiazoles (Padmavati et al.,
2008; Pintilie et al., 2007) have also been proved to be the
most important group of fungicides with systemic activity
and are well known for their pronounced ability to control a
large number of fungal diseases. Some of the 2-substituted-
1,3,4-thiadiazoles have been found to produce the inhibition
of growth of transplanted tumours and leukaemias in mice
(Krakoff et al., 1959). In the interest of above, we have
designed and synthesised a system that combines bio-labile
molecules having Schiff bases and 1,2,4-triazoles deriva-
tised with the 1,3,4-thiadiazoles. The free amino group of
1,3,4-thiadiazole can be easily exploited for condensation
and ring insertion reactions. 1,3,4-Thiadiazole was chosen
S. Bansode ꢀ R. Kamble (&)
Post-Graduate Department of Studies in Chemistry,
Karnatak University, Dharwad 580 003, India
e-mail: kamchem9@gmail.com
123

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Med Chem Res (2012) 21:867–873
in this study because of the effect of its basic functions on
non specific antifungal agents.
carbonyl of compound (1a–d) confirmed the formation of
the Schiff’s base. The proton NMR spectral studies of the
compound (3g–j) showed a singlet responsible for one
proton in the range d 9.46–9.8 ppm due to imine proton.
The other protons viz., the aromatic protons and the sub-
stituents attached to the phenyl group of sydnone and
substituent on the C5-carbon atom of 1,3,4-thiadiazole
appeared in their respective ranges.
Results and discussion
Chemistry
3-Arylsydnone was reacted with a stirred mixture of
N-methylformanilide and phosphorus oxychloride to get
3-aryl-4-formyl-sydnone (1a–d). The compound (1a–d) was
then reacted with 2-amino-5-substituted [1,3,4]-thiadiazole
(2e–f) to get the schiff base, 2-(30-aryl-sydnon-40-ylidene)-
5-substituted-[1,3,4]-thiadiazol-2-yl-amine (3g–n). The efforts
to get azetidinone derivatives (4g–n) by the reaction
of (3g–n) with chloroacetylchloride were unsuccessful
(Scheme 1).
The IR spectral analysis of another set of title com-
pounds viz., (6g–n) has shown the following features.
A sharp band around 1700–1715 cm-1 was observed due
to carbonyl group present in 1,2,4-triazole ring. Its precursor
(5a–d) has shown carbonyl stretching frequency in range
1775 cm-1 (Mallur and Badami, 2000). The decrease in car-
bonyl stretching frequency is a strong indication of formation
of the compound (6g–n). The proton NMR studies of the
compounds (6g–n) showed aromatic protons in their respec-
tive regions. Also, these compounds (6g–n) have shown a
singlet for three protons in the range d 2.29–2.38 ppm due to
C5-methyl protons. Whereas, the compounds (6k–n) have
shown another singlet for the three protons due to methyl
group attached to 1,3,4-thiadiazole ring. The compounds
(6g–n) were also confirmed by the FAB mass spectral studies
and have exhibited the corresponding molecular ion peaks.
In another set of reactions, the 3-arylsydnone was sub-
jected to 1,3-dipolar cycloaddition with acetic anhydride
initiated by bromination to form 3-aryl-5-methyl-2-oxo-D4-
1,3,4-oxadiazole (5a–d). The compound (5a–d) when
refluxed with 1,3,4-thiadiazole derivative (2e–f) in ethanol
at about 80°C gave the compound (6g–n) (Scheme 2).
The possible mechanism of the ring insertion of nitrogen
of the 2-amino-5-substituted-1,3,4-thiadiazole into the
3-aryl-5-methyl-2-oxo-D4-1,3,4-oxadiazole (5a–d) is pro-
posed in the Scheme 3.
In vitro antibacterial and antifungal activity
Spectral analyses
In this study, antimicrobial activities of the newly synthe-
sized compounds were evaluated against four test micro-
organisms viz., bacteria Escherichia coli, Bacillus cereus,
fungi Candida albicans and Aspergillus niger. The com-
parative activities of the newly synthesized compounds
(3g–n) and (6g–n) and the control antibiotics chloram-
phenicol and ketoconazole on bacterial and fungal strains,
respectively, are summarised in Table 1.
The structures of all the newly synthesised compounds
were confirmed by spectral studies and CHN analyses. The
IR of compounds (3g–n) showed two characteristic bands
in the range 1740–1743 and 1660–1663 cm-1 due to syd-
none carbonyl and C=N stretching, respectively. The
absence of sharp band around 1675 cm-1 due to formyl
Scheme 1 Synthetic pathway
of 2-(30-aryl-50-sydnon-40-
ylidene)-5-substituted-[1,3,4]-
thiadiazol-2-yl-amines (3g–n).
a R = phenyl, b R = p-tolyl,
c R = p-anisyl, d R =
p-chlorophenyl, e R0 = phenyl,
f R0 = methyl, g R = phenyl,
R0 = phenyl, h R = p-tolyl,
R0 = phenyl, i R = p-anisyl,
R0 = phenyl, j R =
O
C
H
N
N
R
R
N
N
Abs. EtOH, AcOH
Reflux
C
N
N
C
H
N
C
S
N
C
N
C
R'
O
H2N
O
S
R'
O
O
3g-n
2e-f
1a-d
ClCH2COCl
Cl
O
p-chlorophenyl, R0 = phenyl,
k R = phenyl, R0 = methyl,
l R = p-tolyl, R0 = methyl,
m R = p-anisyl, R0 = methyl,
n R = p-chlorophenyl,
N
N
R
CH
N
N
C
S
N
C
R'
O
R0 = methyl
O
4g-n
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Med Chem Res (2012) 21:867–873
869
O
R
O
N
S
N
N
R
N
N
N
EtOH
heat
N
N
O
N
H2N
R'
S
C
C
R'
CH3
CH3
6g-n
5a-d
2e-f
Scheme 2 Synthetic pathway of 2-aryl-5-methyl-3-oxo-(50-sub-
stituted-[1,3,4]-thiadiazol-20-yl)-2,4-dihydro-[1,2,4]-triazoles (6g–n).
a R = phenyl, b R = p-tolyl, c R = p-anisyl, d R = p-chlorophenyl,
e R0 = phenyl, f R0 = methyl, g R = phenyl, R0 = phenyl, h R =
p-tolyl, R0 = phenyl, i R = p-anisyl, R0 = phenyl, j R = p-chloro-
phenyl, R0 = phenyl, k R = phenyl, R0 = methyl, l R = p-tolyl,
R0 = methyl, m R = p-anisyl, R0 = methyl, n R = p-chlorophenyl,
R0 = methyl
Scheme 3 Proposed
mechanism for the formation of
2-aryl-5-methyl-3-oxo-
(50-substituted-[1,3,4]-
thiadiazol-20-yl)-2,4-dihydro-
[1,2,4]-triazoles (6g–n)
H
N
H
O
N
S
O
R
R
N
N
N
- H+
N
N
N
O
+ H+
N
O
H2N
R'
S
R'
C
C
CH3
CH3
5a-d
2e-f
R
O
O
N
N
S
R
N
N
O
N
S
N
S
R
N
N
N
- H2O
R'
N
R'
N
N
N
H
N
N
H
OH
OH
R'
C
CH3
CH3
6g-n
CH3
The compounds 6h with p-tolyl group and 6i, 6m with
Table 1 The MICs of antibacterial activity of newly synthesized
Schiff bases (3g–n) and triazole derivatives (6g–n)
p-anisylgroup and 6n with p-chlorophenyl groups haveshown
remarkable activity against the E. coli whereas, the other
compounds have shown weak to moderate activity against this
bacterial species. Amongst the compounds tested for the
activity against B. cereus only two compounds viz., 6j and 6n
with p-chlorophenyl group have shown the potent activity
(15.6 lg/ml) where, the standard drug hasshown MIC value at
12.5 lg/ml. The compounds 3i, 3j, 3n, 6h and 6l have
exhibited a moderate inhibition activity against this bacterium.
The compound 3h with p-tolyl group has shown prom-
ising activity against the fungal strain C. albicans with MIC
value 3.9 lg/ml. Whereas, the compounds 3m–n, 6j, and 6n
have shown significant activity against this strain MIC
(7.8 lg/ml). The remaining compounds have shown weak
activity. In case of screening against A. niger, the com-
pounds 6m–n have exhibited the potent activity whereas, the
compound 6j has shown moderate activity. The activity of
the other molecules against this fungus is less.
Entry no.
E. coli
B. cereus
C. albicans
A. niger
3g
31.25
62.5
62.5
31.25
62.5
62.5
15.6
62.5
31.25
15.6
15.6
31.25
62.5
62.5
15.6
15.6
1.95
–
125
125
62.5
62.5
250
125
125
62.5
125
62.5
125
15.6
125
62.5
31.5
15.6
12.5
–
31.25
3.9
125
125
62.5
31.25
125
125
125
125
62.5
62.5
62.5
15.6
62.5
62.5
7.8
3h
3i
62.5
7.8
3j
3k
31.25
31.25
7.8
3l
3m
3n
7.8
6g
31.25
125
6h
6i
31.25
7.8
6j
6k
31.25
62.5
31.25
7.8
6l
6m
6n
7.8
Control 1
Control 2
–
–
Conclusion
0.97
0.97
Minimum inhibitory concentrations (MICs) of compounds and anti-
biotics expressed as (lg/ml); control 1, Chlroamphenicol, control 2,
Ketoconazole
In summary, a series of sydnones derivatised with 1,3,4-thia-
dizoles (3g–n) and [1,3,4]thiadiazol-2’-yl-[1,2,4]-triazoles
123

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Med Chem Res (2012) 21:867–873
(6g–n) were synthesized as potent antimicrobial agents.
The structural design altered bioactivity profile of the title
compounds and indicated a combination of SAR analysis
towards the substituents attached to the sydnone and 1,2,4-
triazoles.
2950 cm-1 (C–H); 1H NMR (CDCl3) d = 2.31 (s, 3H, CH3),
6.96–7.96 (m, 9H, Ar–H), 9.52 (s, 1H, H–C=N) ppm.
Anal. Calcld. for C18H13O2N5S: C, 59.50; H, 3.58; N,
19.28. Found: C, 59.45; H, 3.54; N, 19.26.
2-(30-p-Anisyl-sydnon-40-ylidene)-5-phenyl-[1,3,4]-
thiadiazol-2-yl-amine (3i)
Experimental
Recrystallisation from methanol, yellow needles. Yield
76%, m.p. 200–202°C. IR 1741 cm-1 (C=O), 1662 cm-1
Melting points were determined on a Thomas Hoover
melting point apparatus and are uncorrected. The com-
pounds were routinely checked for their homogeneity by
thin layer chromatography (TLC) using hexane, chloro-
form and methanol (7:2:1) as eluents. The IR spectra were
recorded on Nicolet Impact 410FT IR spectrophotometer
using KBr pellets or Nujol. 1H NMR spectra were recorded
on Bruker 300-MHz FT NMR spectrometer in CDCl3 with
TMS as an internal standard. Mass spectral studies were
carried out using Jeol SX-102 (FAB) and elemental analysis
using Heraus CHN rapid analyser. 3-Aryl-4-formyl-syd-
nones (1a–d) (Thoman et al., 1964), 1,3,4-oxadiazolinones
(5a–d) (Mallur and Badami, 2000) and 2-amino-5-substi-
tuted-[1,3,4]-thiadiazoles (2e–f) (Bernstein et al., 1957) were
synthesized using published procedures.
1
(H–C=N), 2950 cm-1 (–CH); H NMR (CDCl3) d = 3.57
(s, 3H, OCH3), 6.80–7.65 (m, 9H, Ar–H), 9.50 (s, 1H, H–
C=N) ppm.
Anal. Calcd. for C18H13O3N5S: C, 56.99; H, 3.43; N,
18.46. Found: C, 56.94; H, 3.46; N, 18.45.
2-(30-p-Chlorophenyl-sydnon-40-ylidene)-5-phenyl-[1,3,4]-
thiadiazol-2-yl-amine (3j)
Recrystallisation from methanol, yellow needles. Yield
76%, m.p. 103–105°C. IR 1743 cm-1 (C=O), 1660 cm-1
(H–C=N) 2950 cm-1 (–CH3); 1H NMR (CDCl3)
d = 6.96–7.96 (m, 9H, Ar–H), 9.46 (s, 1H, H–C=N) ppm.
Anal. Calcld. for C17H10O2N5SCl: C, 53.26; H, 2.61; N,
18.28. Found: C, 53.24; H, 2.57; N, 18.25.
General procedure for the preparation of 2-(30-aryl-50-
sydnon-40-ylidene)-5-substituted-[1,3,4]-thiadiazol-2-
yl-amines (3g–n)
2-(30-Phenyl-sydnon-40-ylidene)-5-methyl-[1,3,4]-
thiadiazol-2-yl-amine (3k)
An equimolar mixture of 2-amino-5-substituted-1,3,4-
thiadiazole (2e–f, 0.10 mol) and 3-aryl-4-formyl-sydnone
(1a–d, 0.10 mol) in ethanol (50 ml) and acetic acid (2–3
drops) refluxed for 5–6 h. The progress of the reaction was
monitored by TLC. After completion of the reaction,
excess solvent was distilled off, and the residue was
washed with water. The solid separated was filtered and
recrystallised from ethanol to get pale yellow crystals.
Recrystallisation from ethanol, yellow needles. Yield 76%,
m.p. 144–146°C. IR 1742 cm-1 (C=O), 1661 cm-1 (H–
C=N); 1H NMR (CDCl3) d = 2.25 (s, 3H, CH3), 7.05–7.64
(m, 5H, Ar–H), 9.80 (s, 1H, H–C=N) ppm.
Anal. Calcd. for C12H9O2N5S: C, 50.17; H, 3.14; N,
24.39. Found: C, 50.14; H, 3.10; N, 24.40.
2-(30-p-Tolyl-sydnon-40-ylidene)-5-methyl-[1,3,4]-
thiadiazol-2-yl-amine (3l)
2-(30-Phenyl-sydnon-40-ylidene)-5-phenyl-[1,3,4]-
thiadiazol-2-yl-amine (3g)
Recrystallisation from methanol, yellow needles. Yield
66%, m.p. 171–173°C. IR 1743 cm-1 (C=O), 1660 cm-1
(H–C=N), 2940 cm-1 (–CH3); 1H NMR (CDCl3) d = 2.20
(s, 3H, CH3, ArCH3), 2.31 (s, 3H, CH3), 6.84–7.63 (m, 4H,
Ar–H), 9.54 (s, 1H, H–C=N) ppm.
Recrystallisation from ethanol, yellow needles. Yield 80%,
m.p. 157–159°C. IR 1743 cm-1 (C=O), 1663 cm-1 (H–
1
C=N); H NMR (CDCl3) d = 6.96–7.96 (m, 10H, Ar–H),
9.58 (s, 1H, H–C=N) ppm.
Anal. Calcd. for C13H11O2N5S: C, 51.83; H, 3.65; N,
23.25. Found: C, 51.80; H, 3.63; N, 23.27.
Anal. Calcd. for C17H11O2N5S: C, 58.45; H, 3.15; N,
20.05. Found: C, 58.40; H, 3.12; N, 20.00.
2-(30-p-Anisyl-sydnon-40-ylidene)-5-methyl-[1,3,4]-
thiadiazol-2-yl-amine (3m)
2-(30-p-Tolyl-sydnon-40-ylidene)-5-phenyl-[1,3,4]-
thiadiazol-2-yl-amine (3h)
Recrystallisation from ethanol, yellow needles. Yield 76%,
m.p. 200–202°C. IR 1741 cm-1 (C=O), 1661 cm-1 (H–
C=N) 2950 cm-1 (–CH3), 1301 cm-1 (C–O); 1H NMR
Recrystallisation from ethanol, yellow needles. Yield 66%,
m.p. 171–173°C. IR 1742 cm-1 (C=O), 1664 cm-1 (H–C=N),
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Med Chem Res (2012) 21:867–873
871
2-p-Anisyl-5-methyl-3-oxo-[4-(50-phenyl-[1,3,4]-
(CDCl3-d6) d = 2.21 (s, 3H, CH3), 3.45 (s, 3H, OCH3),
6.90–7.76 (m, 4H, Ar–H), 9.57 (s, 1H, H–C=N) ppm.
Anal. Calcld. for C14H13O3N5S: C, 49.21; H, 3.47; N,
22.08. Found: C, 49.24; H, 3.47; N, 22.10.
thiadiazol-20-yl)-2,4-dihydro[1,2,4]-triazole (6i)
Recrystallisation from ethanol; pale yellow needles. Yield
74%. m.p. 144–145°C. IR 1700 cm-1 (C=O), 1633 cm-1
(C=N), 1300 cm-1 (C–O ether); 1H NMR (CDCl3)
d = 2.32 (s, 3H, C5–CH3), 3.50 (s, 3H, OCH3), 7.28–7.94
(m, 9H, Ar–H) ppm; MS (FAB) 365 (15), 321 (5), 313 (10),
279 (20), 262 (5), 220 (30), 211 (75), 178 (100), 154 (85),
136 (80), 121 (70).
2-(3-p-Chlorophenyl-sydnon-4-ylidene)-5-methyl-[1,3,4]-
thiadiazol-2-yl-amine (3n)
Recrystallisation from methanol, yellow needles. Yield
77%, m.p. 109–110°C. IR 1740 cm-1 (C=O), 1662 cm-1
(H–C=N), 2930 cm-1 (–CH3); 1H NMR (CDCl3) d = 2.20
(s, 3H, CH3), 6.80–7.24 (m, 4H, Ar–H), 9.45 (s, 1H, H–
C=N) ppm.
Anal. Calcd. for C18H15ON5S: C, 56.69; H, 3.94; N,
18.37. Found: C, 56.68; H, 3.87; N, 18.34.
Anal. Calcd. for C12H8O2N5SCl: C, 44.86; H, 2.49; N,
21.81. Found: C, 45.03; H, 2.45; N, 21.79.
2-p-Chlorophenyl-5-methyl-3-oxo-4-(50-phenyl-[1,3,4]-
thiadiazol-20-yl)-2,4-dihydro[1,2,4]-triazole (6j)
General procedure for the preparation of 2-aryl-5-
methyl-3-oxo-(50-substituted-[1,3,4]-thiadiazol-20-yl)-
2,4-dihydro-[1,2,4]-triazoles (6g–n)
Recrystallisation from ethanol; pale yellow needles. Yield
82%. m. p. 192–194°C. IR 1712 cm-1 (C=O), 1638 cm-1
(C=N), 1H NMR (CDCl3) d = 2.37 (s, 3H, C5–CH3)
7.28–7.94 (m, 9H, Ar–H) ppm; MS (FAB) 399 (20), 290
(5), 282 (10), 248 (20), 231 (5), 189 (30), 180 (70), 147
(100), 123 (80) 105 (80), 90 (72).
A mixture of 3-aryl-5-methyl-2-oxo-D4-1,3,4-oxadiazole
(5a–d) (0.01 mol) and 2-amino-5-substituted-[1,3,4]-thia-
diazole (2e–f) (0.01 mol) in absolute ethanol (25 ml) was
refluxed for 6 h. The solvent was distilled off, and the
residue was cooled. The solid separated was washed with
water and filtered. Recrystallised from absolute ethanol to
get yellow needles.
Anal. Calcd. for C17H12ON5SCl: C, 52.98; H, 3.12; N,
18.19. Found: C, 52.94; H, 3.19; N, 18.24.
5-Methyl-3-oxo-2-phenyl-4-(50-methyl-[1,3,4]-thiadiazol-
20-yl)-2,4-dihydro-[1,2,4]-triazole (6k)
5-Methyl-3-oxo-2-phenyl-4-(50-phenyl-[1,3,4]-thiadiazol-
20-yl)-2,4-dihydro-[1,2,4] triazole (6g)
Recrystallisation from methanol; pale yellow needles.
Yield 72%. m.p. 175–176°C. IR 1711 cm-1 (C=O),
1645 cm-1 (C=N), 1H NMR (CDCl3) d = 2.20 (s, 3H,
Recrystallisation from ethanol; pale yellow needles. Yield
77%. m. p. 185–187°C. IR 1710 cm-1 (C=O), 1643 cm-1
(C=N), 2923 cm-1 (C–H); 1 H NMR (CDCl3) d = 2.38 (s,
3H, C5–CH3), 7.12–7.94 (m, 10H, Ar–H) ppm; MS (FAB)
335 (20), 291 (10), 283 (15), 249 (20), 232 (10), 190 (60),
181 (70), 148 (100), 124 (75), 106(70), 91 (60).
0
C5 –CH3), 2.38 (s, 3H, C5–CH3), 7.28–7.94 (m, 5H, Ar–H);
MS (FAB) 217 (20), 173 (6), 165 (15), 131 (30), 114 (100),
72 (75), 63 (60), 54 (12), 21 (60).
Anal. Calcd. for C12H11ON5S: C, 52.74; H, 4.02; N,
25.64. Found: C, 52.76; H, 4.00; N, 25.63.
Anal. Calcd. for C17H13ON5S: C, 58.11; H, 3.70; N,
19.94. Found: C, 58.07; H, 3.66; N, 19.78.
5-Methyl-4-(50-methyl-[1,3,4]-thiadiazol-20-yl)-3-oxo-2-
p-tolyl-2,4-dihydro-[1,2,4] triazole (6l)
5-Methyl-3-oxo-4-(50-phenyl-[1,3,4]-thiadiazol-20-yl)-2-
p-tolyl-2,4-dihydro-[1,2,4]-triazole (6h)
Recrystallisation from methanol; pale yellow needles.
Yield 73%. m.p. 197–198°C. IR 1708 cm-1 (C=O),
Recrystallisation from ethanol, pale yellow needles. Yield
72.40%. m. p. 211–213°C. IR 1705 cm-1 (C=O),
1640 cm-1 (C=N–H), 2945 cm-1 (C–H); 1H NMR
(CDCl3) d = 2.24 (s, 3H, ArCH3), 2.29 (s, 3H, C5–CH3),
7.28–7.94 (m, 9H, Ar-H); MS (FAB) 349 (15), 305 (10),
297 (15), 263 (15), 246 (10), 204 (35), 195 (70), 162 (100),
138 (80), 120 (85), 105 (70).
1
1641 cm-1 (C=N), 2940 cm-1 (C–H); H NMR (CDCl3)
0
d = 2.25 (s, 3H, C5 –CH3), 2.30 (s, 3H, ArCH3), 2.41 (s,
3H, C5–CH3), 7.28–7.80 (m, 4H, Ar–H) ppm; MS (FAB)
231 (25), 187 (10), 179 (18), 145 (35), 128 (100), 86 (75),
77 (65), 44 (10), 20 (65).
Anal. Calcd. for C13H13ON5S: C, 54.35; H, 4.52; N,
24.39. Found: C, 54.32; H, 4.50; N, 24.40.
Anal. Calcd. for C18H15ON5S: C, 59.18; H, 4.11; N,
19.18. Found: C, 59.19; H, 4.15; N, 19.15.
123

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Med Chem Res (2012) 21:867–873
2-p-Anisyl-5-methyl-4-(50-methyl-[1,3,4]-thiadiazol-20-yl)-
2,4-dihydro-3-oxo-[1,2,4]-triazole (6m)
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Recrystallisation from ethanol; pale yellow needles. Yield
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Recrystallisation from methanol; pale yellow needles.
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