549
A. S. Shawali et al. • 5-(PyrazoI-5-yl)-l,3,4-oxadiazole-2(3H)-thiones
Table III. Antibacterial activity of compounds 6.
the S-alkylation exhibited by 1,3,4-oxadiazole-
2(3H )-thiones [16] and l,2,4-triazole-3(4H )-thi-
ones [2].
0.2%
0.1%
0.05%
Bacteria
species
Compd.
no.
Cone,
(IZD [cm])
W hen 13af and 13ag w ere treated with benzen-
ediazonium chloride in pyridine, they underw ent
(0.5)
(0.7)
(1.0)
(0-0)
(1-0)
(1-2)
(0.0)
(1-0)
(1.1)
(0.7)
(1.2)
(1.5)
(0.5)
(1.2)
(1.4)
(0-5)
(1.2)
(1.6)
(0.6)
(0.9)
(1.4)
(0.0)
(1.1)
(1.3)
(0.7)
(1.0)
(1.4)
BS
BS
BS
PV
PV
PV
PA
PA
PA
6a
6b
6c
6a
6b
6c
6a
6b
6c
a
Japp-K lingem ann reaction [16] [17] and af-
forded directly the respective products lOaf.ag.
A s the latter reaction is know n to lead to hydra-
zone derivatives as end products, it is not u n rea-
sonable to assum e on the basis of the foregoing
results, that the initially form ed thiohydrazonate
esters 8 underw ent in situ tandem cyclization to
give 9 and ring-chain tautom erism to yield 10
as end products. This result indicates th at both
a V arian G em ini 200 N M R spectrom eter. M ass
spectra w ere recorded on a G C M S-Q P 1000 E X
V arian M A T 711 and SSQ 7000 spectrom eters.
E lem ental analyses were carried out at the Mi-
croanalytical L aboratory of C airo University,
G iza, Egypt.
transform ations studied nam ely (1 +
6 —*■ 10)
and (13 + A rN 2+ —»• 10) proceed via the sam e
interm ediate 8.
The biological evaluations of
6 were carried
Antimicrobial Activity
out at The R egional C enter for M ycology and
B iotechnology of A l-A zhar University, Cairo,
Egypt. The hydrazonoyl chlorides la -d [18] and
the spiro precursors 3a-c [7] w ere prepared as
previously described.
Methyl 1,3,4-triarylpyrazole-5-carboxylates (4):
A m ixture of sodium m ethoxide, prepared from
sodium m etal (0.1 g, 55 m g-atom ) in absolute
m ethanol (50 ml), and the appropriate spiro-az-
The com pounds 6a-c w ere tested for their anti-
m icrobial activities using four fungi species
nam ely A spergillus fum igatus AF, Penicillium
chrysogenum BC, Syncephalastrum racem osum
SR, and C andida albicaus CA as well as five
bacteria species nam ely Salm onella sp. SS, Bacil-
lus subtilis BS, Proteus vulgaris PV, Escherichia
coli EC and Pseudom onas aeruginosa PA were
tested. The organism s w ere tested against the
activity of different concentrations (0.2 % , 0.1 %
and 0.05% ) of each com pound and using inhibi-
tion zone diam eter in cm (IZ D ) as criterion for
the antim icrobial activity. The results show that
while com pounds 6b and 6c are inactive tow ards
all fungi tested, com pound 6a was found active
against the species CA: 6a,% (IZD , cm) : 0.2
(1.3), 0.1 (1.1); 0.05 (0.9).
lactone 3 (5 m m ole) [7] was refluxed for
3 h,
then cooled. The solid that form ed on cooling
was collected, w ashed with w ater, dried and fi-
nally crystallized from acetic acid to give the
respective 4. C om pound 4a was found identical
in all respects with an authentic sam ple [8]. The
physical constants of the hitherto unreported
4b,c are given in Table IV.
l,3,4-Triarylpyrazole-5-carbohydrazides (5):
A
m ixture of the appropriate m ethyl 1,3,4-arylpyra-
zole-5-carboxylate 4 (0.05 m ol) and hydrazine
hydrate (85% , 0.05 m ol) in absolute ethanol
(50 ml) was refluxed for 2 - 3 h, then the excess
solvent was distilled and the residue left was
cooled. The solid that produced was filtered and
crystallized from the appropriate solvent to give
the respective hydrazide 5. The physical con-
stants and yields of the hydrazides 5a-c prepared
are given in Table IV.
5-[(l,3,4-Triaryl)pyrazol-5-yl]-l,3,4-oxadiazole-
2(3H)-thiones (6 ): A solution of potassium hy-
droxide (0.05 m ol) in w ater (10 ml) was added
to ethanol (95% , 200 ml) and to the resulting
solution was added the appropriate hydrazide 5
(0.05 m ol) w ith stirring. A fter the latter dissolved
com pletely, liquid carbon disulfide (3.6 ml, 0.06
Furtherm ore, while com pounds 6a-c exhibit no
inhibition of the two bacteria species SS and EC,
the two derivatives 6b,c w ere found active
against the other three species BS, PV and PA.
C om pound 6a was the least active, how ever. The
results are sum m arized in Table III.
Experimental Section
M elting points were determ ined on a G allen-
kam p apparatus and are uncorrected. IR spectra
w ere recorded in potassium brom ide using P er-
kin E lm er FTIR 1650 and Pye-U nicam SP300
Infrared spectrophotom eters. 'H N M R spectra
w ere recorded in deuterated chloroform using
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