Synthesis and antimicrobial activity of substituted [(pyrazol-4-yl) methylene]hydrazono-2,3-dihydrothiazoles and their sugar derivatives

Article abstract of DOI:10.1002/jhet.668

A number of new [(pyrazol-4-yl)methylene]hydrazono-2,3-dihydrothiazole derivatives, their sugar hydrazones and N-glycosides were synthesized. Furthermore, N-substituted oxygenated alkyl and hydroxyl derivatives and 1,3,4,-oxadiazoline acyclic nucleoside analogs were prepared. The newly synthesized compounds were tested for their antimicrobial activities and showed moderate to high inhibition activities.

Full text of DOI:10.1002/jhet.668

January 2012
Synthesis and Antimicrobial Activity of Substituted
[(Pyrazol-4-yl)methylene]hydrazono-2,3-dihydrothiazoles
and Their Sugar Derivatives
93
Adel A.-H. Abdel-Rahman,a* Wael A. El-Sayed,b* El-Sayed G. Zaki,a
Asem A. Mohamed,c and Ahmed A. Faddad
aChemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt
bPhotochemistry Department, National Research Center, El Dokki, Cairo, Egypt
cChemistry of Natural and Microbial Products Department, National Research Center,
El Dokki, Cairo, Egypt
dChemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt
*E-mail: adelnassar63@hotmail.com or waelshendy@gmail.com
Received June 20, 2010
DOI 10.1002/jhet.668
Published online 12 October 2011 in Wiley Online Library (wileyonlinelibrary.com).
A number of new [(pyrazol-4-yl)methylene]hydrazono-2,3-dihydrothiazole derivatives, their sugar
hydrazones and N-glycosides were synthesized. Furthermore, N-substituted oxygenated alkyl and hydroxyl
derivatives and 1,3,4,-oxadiazoline acyclic nucleoside analogs were prepared. The newly synthesized
compounds were tested for their antimicrobial activities and showed moderate to high inhibition activities.
J. Heterocyclic Chem., 49, 93 (2012).
INTRODUCTION
[15], antimalarial [16] and antiviral activities [17,18].
As far as the anticancer activity is concerned, literature
citation revealed that a wide range of pyrazole deriva-
tives were reported to contribute to a variety of antineo-
plastic potentials against a wide range of cancer cell
lines [19,20]. On the other hand, thiazole derivatives are
considered as one of the most important classes of heter-
ocyclic compounds; their derivatives are characterized
with high biological activity in pharmaceutical fields
and have showed antibacterial [21], antifungal [22], anti-
tumer [23], antiviral [23,24], anti-inflammatory [25], and
antineoplastic [26] activities as well as inhibitory activ-
ity of growth of gastrointestinal [27,28], biliary and pan-
creatic adenocarcinoma cells [29].
The chemistry of 1H-pyrazole containing compounds
is particularly interesting because of their potential
application in medicinal chemistry as analgesic [1,2],
anti-inflammatory [3], antitumor [4,5], antimicrobial [6–
9] and therapeutic agents [10], as well as based on their
wide applications in agriculture as potent insecticides
[11] and herbicides [12], although scarcely found in na-
ture [13]. Due to many promising pharmacological,
agrochemical, and analytical applications, a number of
substituted pyrazoles are being used as inhibitors of
heat-shock protein 90 (HSP90) and as therapeutics of
cancer and therefore they have been the focus of many
synthetic targets over the past decades [14]. 1H-Pyrazole
based heterocyclic structures have also attracted syn-
thetic interest for being an essential moieties in many
chemotherapeutic agents with potential antiparasitic
The thioglycosyl heterocycles [30–33] and the acyclic
nucleoside analogs with modified glycon part and the
heterocyclic base have stimulated extensive research as
C
V
2011 HeteroCorporation

94
A. A. Abdel-Rahman, W. A. El-Sayed, E. G. Zaki, A. A. Mohamed, and A. A. Fadda
Vol 49
Scheme 1
biological inhibitors [34–36]. In view of the above find-
ings and our interest in the attachment of sugar moieties
to newly synthesized heterocycles [37–39], we report in
the present work the synthesis of new substituted [(pyra-
zol-4-yl)methylene]hydrazono-2,3-dihydrothiazole deriv-
atives and their substituted sugar derivatives.
Reaction of 2 with thiosemicarbazide in ethanol at
reflux temperature gave the corresponding hydrazinecar-
bothioamide derivative 3 in 88% yield. Treatment of 3
with equivalent amount of phenacyl bromide and anhy-
drous sodium acetate in absolute ethanol under reflux
gave the corresponding substituted 2,3-dihydrothiazole
derivative 4 in 78% yield. The structure of the substituted
dihydrothiazole derivative was confirmed by IR, H and
13C NMR and mass spectra which agreed with the
1
assigned structure. The H NMR spectrum showed the
1
RESULTS AND DISCUSSION
Chemistry. In this investigation, reaction of biphenyl
methyl ketone phenyl hydazone (1) with phosphorus oxy-
chloride in dimethylformamide (DMF) at 0ꢀC afforded 3-
(biphenyl-4-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (2)
in 90% yield. The synthesis of the pyrazole-4-carbalde-
hyde derivative 2 was carried out according to reported
methods [40,41] by applying the Vilsmeier-Haack
reaction. The formylating agent, also known as the Vils-
meyer-Haack Reagent, is formed in situ from DMF and
phosphorus oxychlorid. An electrophilic substitution leads
to a-chloro amines, which are rapidly hydrolyzed during
work up to give the aldehyde. The IR spectrum of 2
showed the bands at 1719 and 1605 cmꢁ1 corresponding
singlet signal at 5.86 ppm for the thiazole H-5 in addition
to the aromatic protons at 7.19–7.96 ppm and the NH at
9.82 ppm. The 13C NMR spectrum revealed the presence
of the signals at 107.71, 155.11, and 158.29 correspond-
ing to thiazole C-5, C-4, and C-2, respectively. Treatment
of 4 with ethyl chloroacetate in the presence of anhydrous
potassium carbonate in DMF at room temperature
1
afforded the ethyl ester derivative 5 in 90% yield. Its H
NMR spectrum showed the methyl group as triplet at
1.48 ppm and the CH2 as quartet at 4.11 ppm in addition
to the signal corresponding to aryl protons. The acid hy-
drazide 6 was obtained in 87% yield by treating of 5 with
hydrazine hydrate in ethanol under reflux (Scheme 1).
Alkylation of the substituted thiazole 4 with chloroe-
thylmethyl ether, 2-(2-chloroethoxy)ethanol, and a-
1
to C¼¼O and C¼¼N. The H NMR spectrum showed sig-
nals at 7.20–7.95 ppm corresponding to aryl and pyrazole
H-3 protons in addition to the signal at 9.75 for the CHO.
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January 2012
Synthesis and Antimicrobial Activity of Substituted [(Pyrazol-4-yl)-
methylene]hydrazono-2,3-dihydrothiazoles and Their Sugar Derivatives
95
Scheme 2
92% yields. It has been reported [42–-45] that when the
acetylation of sugar hydrazones was carried out at high
temperature in boiling acetic anhydride, cyclization usu-
ally takes place in addition to per-O-acetylation to
afford C-nucleoside analogs. We reported previously
[42] the synthesis of N-acetyl 1,3,4-oxadiazoline acyclic
nucleoside analogs by the reaction of sugar hydrazones
with boiling acetic anhydride. However, when the hydra-
zinyl sugars 13–15 were heated in acetic anhydride at
100ꢀC they gave the corresponding N-acetyl 1,3,4-oxa-
diazoline acyclic nucleoside analogs 19–21 in 73–78%
yields, respectively (Scheme 3). The IR spectra of 19–21
showed characteristic absorption bands in the carbonyl
frequency region at 1665–1666 and 1741–1745 cmꢁ1 cor-
responding to the carbonyl amide and the carbonyl ester
groups, respectively indicating the presence of N-acetyl
1
group in addition to the O-acetyl groups. Their H NMR
spectra showed the signals of the O-acetyl-methyl protons
each as singlet in the range d 1.90–2.05 ppm and the N-
acetyl-methyl protons in the range d 2.20–2.22 ppm. The
13C NMR spectrum of 19–21 showed the resonances of
the acetyl-methyl carbons at d 20.12–29.75 ppm. The
value of the chemical shift of the C-N-Ac (C-1 in the
original sugar chain moiety) appeared at d 90.12 and
90.49 ppm whose value indicated its N,N-acetal nature
rather than being a C¼¼N group.
Antimicrobial activity. The target compounds were
screened in vitro for their antimicrobial activities against
Escherichia coli NRRL B-210 (Gram -ve bacteria), Ba-
cillus subtilis NRRL B-543 and Staphylococcus aureus
(Gram þve bacteria), Aspergillus niger, and Candida
albicans NRRL Y-477 (Fungi).
acetobromoglucose gave the corresponding alkylated
derivatives 7–9 in 75–90% yields. Deprotection of the
acetylated sugar of unnatural nucleoside derivative 9
using a methanolic ammonia solution afforded the free
hydroxyl nucleoside 10 in 91% yield (Scheme 2). The
structures of these alkylated products were proved by
The results of antimicrobial activity (Table 1) indi-
cated that compounds 1–4, 6, 7, 10–14, 16, and 22 (13
out of 22 tested compounds) displayed high activity
against the five micro-organisms. Other compounds
have been shown to possess little activity or totally inac-
tive. These results revealed the importance pyrazolyl
and 1,3-thiazolidinyl ring systems as basic structural
constituents in the synthesized compounds.
1
IR, H NMR, and mass spectra which agreed with the
assigned structure.
Treatment of the acid hydrazide 6 with the substituted
aromatic aldehydes; p-chlorobenzaldehyde and 3,4,5-tri-
methoxybenzaldehyde afforded the corresponding N-ary-
lideneacetohydrazides 11 and 12 in 89–91% yields. Fur-
thermore when the hydrazide 6 was allowed to react
with the monosaccharides; D-galactose, D -mannose or D
-xylose the corresponding sugar hydrazones 13–15 were
From the results of antimicrobial activity and struc-
ture-activity relationship it was interesting to notice that
the attachment of certain acetylated open sugar moieties
or glycosyl moiety to substituted 1,3-thiazolidinyl ring
system resulted in marked loss of antimicrobial activity.
Furthermore, no significant differences in inhibition
activities were remarked as a result of changing the sub-
stituent in the para position in the aromatic ring in the
synthesized substituted arylideneacetohydrazides. More-
over, the ribotetritolyl acyclonucleoside analogous of the
1,3,4-oxadiazolinyl base showed higher inhibition activ-
ity then the corresponding galacto- or mannopentitolyl
sugar moieties and the corresponding acetylated sugar
hydrazones.
1
obtained in 82–92% yields. The H NMR spectra of 13–
15 showed the signals corresponding to the alditolyl
chain protons and sugar hydroxyl groups. The C-1
methine proton appeared as doublet at 7.51–7.55 ppm.
Acetylation of 13–15 either with acetic anhydride in
pyridine at room temperature afforded the corresponding
per-O-acetyacetylated sugar hydrazones 16–18 in 88–
Journal of Heterocyclic Chemistry
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96
A. A. Abdel-Rahman, W. A. El-Sayed, E. G. Zaki, A. A. Mohamed, and A. A. Fadda
Vol 49
Scheme 3
and 200 MHz with TMS as internal standard. Chemical shifts
were reported in d scale (ppm) relative to TMS as a standard,
and the coupling constants (J values) are given in Hz. The pro-
gress of the reactions was monitored by TLC using aluminum
silica gel plates 60 F245. EI-mass spectra were recorded with a
HP D5988 A 1000 MHz instrument (Hewlett-Packard, Palo
Alto, CA).
3-(Biphenyl-4-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (2). To
an ice cold dimethylformamide (10 mL) was added dropwise
with stirring phosphorus oxychloride (1.53 g, 10 mmol) over a
period of 30 min, stirring was continued for further 45 min.
keeping the reaction mixture at 0ꢀC, biphenyl methyl ketone
phenyl hydrazone (2.86 g, 10 mmol) was then added and the
reaction mixture was allowed to attain room temperature. The
mixture was heated under reflux for 2 h, allowed to cool, and
In conclusion, a number of new [(pyrazol-4-yl)methy-
lene]hydrazono-2,3-dihydrothiazoles, sugar hydrazones,
and their N-glycoside derivatives were synthesized and
most of them displayed high inhibition activities. Com-
pounds incorporating free hydroxyl sugar moieties dis-
played higher activities than the corresponding acety-
lated analogs.
EXPERIMENTAL
General. Melting points were determined using a Bu¨chi
apparatus. IR spectra (KBr) were recorded with a Bruker-Vec-
1
tor22 instrument (Bruker, Bremen, Germany). H NMR spectra
were recorded with a Varian Gemini spectrometer at 300 MHz
Journal of Heterocyclic Chemistry
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January 2012
Synthesis and Antimicrobial Activity of Substituted [(Pyrazol-4-yl)-
methylene]hydrazono-2,3-dihydrothiazoles and Their Sugar Derivatives
97
Table 1
In vitro antimicrobial activity by agar diffusion method of tested compounds.
Microorganisms
Candida
albicans
Tested compounds
Sample wt.
Escherichia coli
Bacillus subtilis
Staph. aureus
Aspergillus niger
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
0.33 g
0.34 g
0.42 g
0.33 g
0.29 g
0.20 g
0.06 g
0.20 g
0.22 g
0.06 g
0.31 g
0.55 g
0.48 g
0.05 g
0.31 g
0.05 g
0.31 g
0.33 g
0.30 g
0.22 g
0.18 g
0.14 g
þþ ve
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þve, zone of inhibition 10 mm or less.
þþve, zone of inhibition 20 mm or less.
ꢁve, no inhibition.
then poured onto ice cold water (100 mL). The mixture was
boiled and the copious white precipitate obtained after cooling
was filtered off, dried, and recrystallized from methanol. Yel-
low solid 2.916 g (90%), m.p. 225–226ꢀC; ir (KBr) m: 1719
dium acetate. The reaction mixture was heated under reflux for
5 h, partially concentrated and left to cool overnight. The sepa-
rated solid product was filtered off and recrystallized from
aqueous ethanol. Yellow solid (3.87 g, 78%), m.p. 197–198ꢀC;
1
1
(C¼¼O), 1605 (C¼¼N) cmꢁ1; H NMR (DMSO-d6, 300 MHz):
ir (KBr) m: 3316 (NH), 1610 cmꢁ1 (C¼¼N); H NMR (DMSO-
d 7.20 (d, J ¼ 8.5 Hz, 2H, ArAH), 7.55 (d, J ¼ 8.2 Hz, 2H,
ArAH), 7.62 (m, 4H, ArAH, pyrazole H-3), 7.69 (d, J ¼ 8.5
Hz, 2H, ArAH), 7.82 (m, 3H, ArAH), 7.95 (d, J ¼ 8.2 Hz,
2H, ArAH), 9.75 (s,1H, CHO); ms m/z (%): 324 (Mþ, 8).
Anal. Calcd. for C22H16N2O: C, 81.46; H, 4.97; N, 8.64.
Found: C, 81.30; H, 4.89; N, 8.49%.
d6, 300 MHz): d 5.86 (s, 1H, thiazole H-5), 7.19 (d, 2H, J ¼
8.5 Hz, ArAH), 7.51 (m, 4H, ArAH), 7.58 (s, 1H, CH¼¼N),
7.64 (m, 4H, ArAH, pyrazole H-3), 7.70 (d, 2H, J ¼ 8.5 Hz,
ArAH), 7.79 (m, 2H, ArAH), 7.86 (m, 4H, ArAH), 7.96 (d,
2H, J ¼ 8.2 Hz, ArAH), 9.82 (s, 1H, NH); 13C NMR (CDCl3,
75 MHz): d 107.71 (thiazole C-5), 123.80–142.48 (ArAC, pyr-
azole C-4,5), 153.51 (C¼¼N), 154.14 (pyrazole C-3), 155.11
(thiazole C-4), 158.29 (thiazole C-2). ms m/z (%): 497 (Mþ,
12). Anal. Calcd. for C31H23N5S: C, 74.82; H, 4.66; N, 14.07.
Found: C, 74.63; H, 4.49; N, 13.85%.
Ethyl 2-{2-[[(3-(biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]
methyl-ene]hydrazono}-4-phenylthiazol-3(2H)-yl)acetate (5). To
a solution of the substituted thiazole 4 (2.46 g, 5 mmol) and
anhydrous potassium carbonate (0.69 g, 5 mmol) in DMF (25
mL), was added ethyl chlorocetate (0.61 g, 5 mmol). The solu-
tion was stirred at room temperature for 12 h and then poured
on ice-cold water. The resulting precipitate was filtered off
and recrystallized from ethanol. White solid 2.62 g (90%),
2-{[3-(Biphenyl-4-yl)-1-phenyl-1H-pyrazol-4-yl]methylene}-
hydra-zinecarbothioamide (3). To a solution of the aldehyde
derivative 2 (3.24 g, 10 mmol) in ethanol (25 mL) was added
an equivalent amount of thiosemicarbazide. The mixture was
heated under reflux for 5 h, filtered off, dried, and recrystal-
lized from ethanol. Yellow solid 3.49 g (88%), m.p. 246–
247ꢀC; ir (KBr) m: 3387 (NH2), 3321 (NH), 1608 (C¼¼N)
1
cmꢁ1; H NMR (DMSO-d6, 300 MHz): d 5.71 (bs, 2H, NH2),
7.18 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.52 (d, 2H, J ¼ 8.2 Hz,
ArAH), 7.57 (s, 1H, CH¼¼N), 7.63 (m, 4H, ArAH, pyrazole
H-3), 7.72 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.86 (m, 3H, ArAH),
7.98 (d, 2H, J ¼ 8.2 Hz, ArAH), 9.12 (s, 1H, NH); ms m/z
(%): 397 (Mþ, 12). Anal. Calcd. for C23H19N5S: C, 69.50; H,
4.82; N, 17.62. Found: C, 69.31; H, 4.77; N, 17.50%.
2-{[[3-(Biphenyl-4-yl)-1-phenyl-1H-pyrazol-4-yl]methylene]-
hydra-zono}-4-phenyl-2,3-dihydrothiazole (4). To a solution of
3 (3.97 g, 10 mmol) in absolute ethanol (20 mL) was added
the equivalent amount of phenyl bromide and anhydrous so-
m.p. 155–156ꢀC; ir (KBr) m: 1739 (C¼¼O), 1610 (C¼¼N) cmꢁ1
;
1H NMR (DMSO-d6, 300 MHz): d 1.48 (t, 3H, J ¼ 5.4 Hz,
CH3), 4.11 (q, 2H, J ¼ 5.4 Hz, CH2), 4.88 (s, 2H, CH2), 5.89
(s, 1H, thiazole H-5), 7.21 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.50
(m, 4H, ArAH), 7.57 (s, 1H, CH¼¼N), 7.64 (m, 4H, ArAH,
pyrazole H-3), 7.71 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.79 (m, 2H,
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A. A. Abdel-Rahman, W. A. El-Sayed, E. G. Zaki, A. A. Mohamed, and A. A. Fadda
Vol 49
ArAH), 7.88 (m, 4H, ArAH), 7.97 (d, 2H, J ¼ 8.2 Hz,
ArAH); MS m/z (%): 583 (Mþ, 9). Anal. Calcd. for
C35H29N5O2S: C, 72.02; H, 5.01; N, 12.00. Found: C, 71.89;
H, 4.98; N, 11.90%.
[(0.28 g, 5 mmol) in distilled water (3 mL)] was added a solu-
tion of 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bromide
(2.06 g, 5 mmol) in acetone (20 mL). The reaction mixture
was stirred at room temperature for 7 h (TLC). The solvent
was evaporated under reduced pressure at 40ꢀC and the residue
was washed with distilled water to remove the formed potas-
sium bromide. The product was dried, and recrystallized from
ethanol. Yellow solid 3.72 g (90%), m.p. 151–152ꢀC; ir (KBr)
2-{2-[[(3-(Biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]methylene)-
hydrazono]-4-phenylthiazol-3(2H)-yl}acetohydrazide (6). A solu-
tion of the ethyl ester derivative 5 (5.83 g, 10 mmol) and
hydrazine hydrate (0.5 g, 10 mmol) in ethanol was heated
under reflux for 6 h. The solution was cooled and the resulting
precipitate was filtered off and recrystallized from ethanol.
White solid 4.82 g (87%), m.p. 205–206ꢀC; ir (KBr) m: 3279
1
m: 1744 (C¼¼O), 1612 (C¼¼N) cmꢁ1; H NMR (DMSO-d6, 300
MHz): d 1.87, 1.88, 2.05, 2.09 (4s, 12H, 4CH3), 3.88 (m, 1H,
H-5), 4.18 (dd, 1H, J ¼ 11.4 Hz, J ¼ 2.8 Hz, H-60), 4.18 (m,
1H, H-600), 4.52 (s, 2H, CH2), 4.75 (t, 1H, J ¼ 9.3 Hz, H-40),
1
(NH2), 3227 (NH), 1668 (C¼¼O), 1610 (C¼¼N) cmꢁ1; H NMR
4.88 (dd, 1H, J ¼ 9.6 Hz, J3 ,4 ¼ 9.3 Hz, H-30), 5.14 (t, 1H, J
¼ 9.6 Hz, H-20), 5.72 (d, 1H, J ¼ 9.8 Hz, H-10), 5.81 (s, 1H,
thiazole H-5), 7.21 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.51 (m, 4H,
ArAH), 7.58 (s, 1H, CH¼¼N), 7.62 (m, 4H, ArAH, pyrazole
H-3), 7.72 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.78 (m, 2H, ArAH),
7.86 (m, 4H, ArAH), 7.98 (d, 2H, J ¼ 8.2 Hz, ArAH); 13C
NMR (CDCl3, 75 MHz): d 19.30, 19.54, 20.18, 20.25 (4CH3),
62.88 (C-60), 64.20 (C-40), 68.65 (C-30), 70.37 (C-20), 71.84
(C-50), 88.96 (C-10), 107.72 (thiazole C-5), 122.80–142.47 (Ar-
C, thiazole C-4, pyrazole C-4,5), 153.51, 154.14, 156.29
(3C¼¼N), 169.78, 170.14, 170.56, 170.84 (4C¼¼O). ms m/z
(%): 827 (Mþ, 7). Anal. Calcd. for C45H41N5O9S: C, 65.28; H,
4.99; N, 8.46. Found: C, 65.02; H, 4.81; N, 8.30%.
0
0
(DMSO-d6, 300 MHz): d 5.08 (s, 2H, CH2), 5.41 (s, 2H,
NH2), 5.88 (s, 1H, thiazole H-5), 7.20 (d, 2H, J ¼ 8.5 Hz,
ArAH), 7.51 (m, 4H, ArAH), 7.58 (s, 1H, CH¼¼N), 7.65 (m,
4H, Ar¼¼H, pyrazole H-3), 7.73 (d, 2H, J ¼ 8.5 Hz, ArAH),
7.78 (m, 2H, ArAH), 7.86 (m, 4H, ArAH), 7.96 (d, 2H, J ¼
8.2 Hz, ArAH), 10.02 (s, 1H, NH); ms m/z (%): 569 (Mþ, 9).
Anal. Calcd. for C33H27N7OS: C, 69.57; H, 4.78; N, 17.21.
Found: C, 69.38; H, 4.45; N, 17.38%.
2-{[[3-(Biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]methylene]-
hydrazono}-3-(2-methoxyethyl)-4-phenyl-2,3-dihydrothiazole (7). To
a solution of the substituted thiazole 4, (4.97 g, 10 mmol) and
anhydrous potassium carbonate (1.38 g, 10 mmol) in DMF (25
mL), was added chloroethylmethyl ether (0.94 g, 10 mmol).
The solution was stirred at room temperature for 12 h and
then poured on ice-cold water. The resulting precipitate was
filtered off and recrystallized from ethanol. Yellow solid 4.16
2-{[[3-(Biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]methylene]-
hydrazono}-3-(ß-D-glucopyranosyl)-4-phenyl-2,3-dihydrothia-
zole (10). A solution of the thiazole glycoside 9 (8.27 g, 10
mmol) in methanolic ammonia solution (150 mL) was stirred
at room temperature for 7 h. The solvent was evaporated under
reduced pressure and the residue was dissolved in absolute
ethanol (10 mL) and left over night to give the free glycoside
10 as a yellow solid. Yellow solid 5.93 g (91%ꢁ),1 m.p. 196–
1
g (75%), m.p. 171–172ꢀC; ir (KBr) m: 1612 (C¼¼N) cmꢁ1; H
NMR (DMSO-d6, 300 MHz): d 3.84 (s, 3H, OCH3), 4.25 (t,
2H, J ¼ 6.2 Hz, CH2), 4.74 (t, 2H, J ¼ 6.2 Hz, CH2), 5.87 (s,
1H, thiazole H-5), 7.22 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.53 (m,
4H, ArAH), 7.58 (s, 1H, CH¼¼N), 7.64 (m, 4H, ArAH, pyraz-
ole H-3), 7.72 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.79 (m, 2H,
ArAH), 7.86 (m, 4H, ArAH), 7.96 (d, 2H, J ¼ 8.2 Hz,
ArAH); ms m/z (%): 555 (Mþ, 9). Anal. Calcd. for
C34H29N5OS: C, 73.49; H, 5.26; N, 12.60. Found: C, 73.31; H,
5.18; N, 12.39%.
197ꢀC; ir (KBr) m: 3398 (OH), 1612 (C¼¼N) cm
;
1H NMR
(DMSO-d6, 300 MHz): d 3.88 (m, 2H, H-60,600), 4.15 (m, 2H,
H-40,50), 4.47 (s, 2H, CH2), 4.24 (m, 2H, H-20,30), 5.74 (d, 1H,
J ¼ 9.8 Hz, H-10), 5.88 (s, 1H, thiazole H-5), 7.19 (d, 2H, J ¼
8.5 Hz, ArAH), 7.51 (m, 4H, ArAH), 7.59 (s, 1H, CH¼¼N),
7.65 (m, 4H, ArAH, pyrazole H-3), 7.71 (d, 2H, J ¼ 8.5 Hz,
ArAH), 7.80 (2H, m, ArAH), 7.87 (m, 4H, ArAH), 7.98 (d,
2H, J ¼ 8.2 Hz, ArAH); ms m/z (%) 659 (Mþ, 12). Anal.
Calcd. for C37H33N5O5S: C, 67.36; H, 5.04; N, 10.62. Found:
C, 67.05; H, 4.91; N, 10.31%.
2-{2-[2-[[[3-(Biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]methy-
lene]-hydrazono]-4-phenylthiazol-3(2H)-yl]ethoxy}ethanol (8). To
a solution of the substituted thiazole 4 (4.97 g, 10 mmol) and
potassium hydroxide (0.56 g, 10 mmol) in absolute ethanol
(20 mL) was added 2-(2-chlorethoxy)ethanol (1.24 g, 10
mmol). The reaction mixture was heated under reflux for 6 h
and the precipitated solid material was filtered. The solvent
was concentrated under reduced pressure and after cooling the
precipitated solid material was filtered off and dried. White
foam 4.62 g (79%); ir (KBr) m: 3426 (OH), 1612 (C¼¼N)
N’-Arylidene-2-{2-[[[3-(biphenyl-3-yl)-1-phenyl-1H-pyrazol-
4-yl]methylene]hydrazono]-4-phenylthiazol-3(2H)-yl}acetohy-
drazide (11 and 12). General procedure. To a well stirred so-
lution of the respective aldehyde (100 mmol) and glacial acetic
acid (0.2 mL) in ethanol (25 mL) was added the acid hydra-
zide 6, (100 mmol). The mixture was heated under reflux for
5–6 h. and the resulting solution was concentrated and left to
cool. The formed precipitate was filtered off, washed with
water and ethanol and then dried.
1
cmꢁ1; H NMR (DMSO-d6, 300 MHz): d 3.96 (t, 2H, J ¼ 6.2
Hz, CH2), 4.12 (t, 2H, J ¼ 6.6 Hz, CH2), 4.25 (m, 2H, CH2),
4.74 (t, 2H, J ¼ 6.6 Hz, CH2), 5.89 (s, 1H, thiazole H-5), 7.20
(d, 2H, J ¼ 8.5 Hz, ArAH), 7.51 (m, 4H, ArAH), 7.57 (s, 1H,
CH¼¼N), 7.65 (m, 4H, ArAH, pyrazole H-3), 7.70 (d, 2H, J ¼
8.5 Hz, ArAH), 7.83 (m, 2H, ArAH), 7.86 (m, 4H, ArAH),
7.99 (d, 2H, J ¼ 8.2 Hz, ArAH); ms m/z (%): 585 (Mþ, 10).
Anal. Calcd. for C35H31N5O2S: C, 71.77; H, 5.33; N, 11.96.
Found: C, 71.50; H, 5.19; N, 11.74%.
2-{2-[[[3-(biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]methylene]
hydra-zono]-4-phenylthiazol-3(2H)-yl}-N’-(4-chlorobenzylidene)
aceto-hydrazide (11). White solid 0.62 g (89%), m.p. 200–
1
201ꢀC; ir (KBr) m: 1681 (C¼¼O), 1612 cmꢁ1 (C¼¼N); H NMR
(DMSO-d6, 300 MHz): d 5.11 (s, 2H, CH2), 5.89 (s, 1H, thia-
zole H-5), 7.26 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.54 (m, 4H,
ArAH), 7.59 (m, H, CH¼¼N), 7.64 (m, 4H, ArAH, pyrazole
H-3), 7.73 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.82 (m, 4H, ArAH),
7.88 (m, 4H, ArAH), 7.97 (m, 3H, ArAH), 10.17 (s, 1H, NH);
2-{[[3-(Biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]methylene]-
hydrazono}-3-(2,3,4,6-tetra-O-acetyl-ß-D-glucopyranosyl)-4-phe-
nyl-2,3-dihydrothiazole (9). To a solution of the substituted thi-
azole 4 (2.48 g, 5 mmol) in aqueous potassium hydroxide
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2012
Synthesis and Antimicrobial Activity of Substituted [(Pyrazol-4-yl)-
methylene]hydrazono-2,3-dihydrothiazoles and Their Sugar Derivatives
99
ms m/z (%): 692 (Mþ, 10). Anal. Calcd. for C40H30ClN7OS:
C, 69.40; H, 4.37; N, 14.16. Found: C, 69.12; H, 4.29; N,
14.30%.
2-{2-[[[3-(Biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]methylene]-
hydrazono]-4-phenylthiazol-3(2H)-yl}-N’-(3,4,5-trimethoxyben-
zyl-idene)acetohydrazide (12). White solid 0.68 g (91%), m.p.
7.69 (m, 4H, ArAH, pyrazole H-3), 7.75 (d, 2H, J ¼ 8.5 Hz,
ArAH), 7.79 (m, 2H, ArAH), 7.86 (m, 4H, ArAH), 7.98 (d,
2H, J ¼ 8.2 Hz, ArAH), 10.22 (s, 1H, NH); ms m/z (%): 701
(Mþ, 10). Anal. Calcd. for C38H35N7O5S: C, 65.03; H, 5.03;
N, 13.97. Found: C, 64.96; H, 4.94; N, 13.72%.
O-Acetyl-sugar 2-{2-[[(3-(biphenyl-3-yl)-1-phenyl-1H-pyra-
zol-4-yl]methylene)hydrazono]-4-phenylthiazol-3(2H)-yl}aceto-
hydrazones (16-18). General procedure. To a solution of the
sugar hydrazones 13–15, (1 mmol) in pyridine (7 mL) was
added acetic anhydride (10 mmol) and stirred at room temper-
ature for 6–8 h. The resulting solution was poured onto
crushed ice, and the product that separated out was filtered off,
washed with a saturated solution of sodium hydrogen carbon-
ate followed by water and then dried.
208–209ꢀC; ir (KBr) m: 1680 (C¼¼O), 1610 (C¼¼N) cmꢁ1
;
1H
NMR (DMSO-d6, 300 MHz): d 3.82 (s, 3H, OCH3), 3.93 (s,
6H, 2OCH3), 5.14 (s, 2H, CH2), 5.88 (s, 1H, thiazole H-5),
7.23 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.55 (m, 4H, ArAH), 7.59
(s, 1H, CH¼¼N), 7.69 (m, 4H, ArAH, pyrazole H-3), 7.73 (d,
2H, J ¼ 8.5 Hz, ArAH), 7.84 (m, 4H, ArAH), 7.88 (m, 4H,
ArAH), 7.98 (d, 2H, J ¼ 8.2 Hz, ArAH), 10.21 (s, 1H, NH);
ms m/z (%): 747 (Mþ, 10). Anal. Calcd. for C43H37N7O4S: C,
69.06; H, 4.99; N, 13.11. Found: C, 69.16; H, 4.84; N,
13.05%.
2,3,4,5,6-Penta-O-acetyl-D-galactose-2-{2-[[(3-(biphenyl-3-yl)-
1-phenyl-1H-pyrazol-4-yl]methylene)-hydrazono]-4-phenylthia-
zol-3(2H)-yl}acetohydrazone (16). White solid 0.87 g (92%),
m.p. 147–148ꢀC; ir (KBr) m 1740 (C¼¼O), 1668 (C¼¼O), 1610
Sugar 2-{2-[[(3-(biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]
methylene)hydrazono]-4-phenylthiazol-3(2H)-yl}acetohydrazones
(13-15). General procedure. To a well stirred solution of the
respective monosaccharide (10 mmol) in water (2 mL), and
glacial acetic acid (0.2 mL) was added 6 (10 mmol) in ethanol
(10 mL). The mixture was heated under reflux for 6 h, and the
resulting solution was concentrated and left to cool. The
formed precipitate was filtered off, washed with water and
ethanol, then dried and recrystallized from ethanol.
(C¼¼N) cmꢁ1
;
1H NMR (DMSO-d6, 300 MHz): d 1.91, 1.94,
1,98, 2.02, 2.04 (5s, 15H, 5CH3), 3.88 (dd, 1H, J ¼ 11.4 Hz, J
¼ 2.8 Hz, H-60), 4.18 (m, 1H, H-600), 4.24 (m, 1H, H-50), 4.75
(t, 1H, J ¼ 9.3 Hz, H-40), 4.88 (dd, 1H, J ¼ 9.6 Hz, J ¼ 9.3 Hz,
H-30), 5.14 (t, 1H, J ¼ 9.6 Hz, H-20), 5.18 (s, 2H, CH2), 5.87 (s,
1H, thiazole H-5), 7.19 (d, 2H, J ¼ 8.5 Hz, Ar-H), 7.50 (m, 4H,
ArAH), 7.54 (d, 1H, J ¼ 7.8 Hz, H-10), 7.59 (s, 1H, CH¼¼N),
7.66 (m, 4H, ArAH, pyrazole H-3), 7.70 (d, 2H, J ¼ 8.5 Hz,
ArAH), 7.80 (m, 2H, ArAH), 7.86 (m, 4H, ArAH), 7.97 (d, 2H,
J ¼ 8.2 Hz, ArAH), 10.26 (s, 1H, NH); ms m/z (%): 941 (Mþ,
12). Anal. Calcd. for C49H47N7O11S: C, 62.48; H, 5.03; N,
10.41. Found: C, 61.37; H, 4.94; N, 10.18%.
D-Galactose 2-{2-[[(3-(biphenyl-3-yl)-1-phenyl-1H-pyrazol-
4-yl]methyl-ene)hydrazono]-4-phenylthiazol-3(2H)-yl}acetohy-
drazone (13). Yellow solid 6.72 g, (92%), m.p. 198–199ꢀC; ir
(KBr) m: 3372–3351 (OH), 1668 (C¼¼O), 1610 (C¼¼N) cmꢁ1
;
1H NMR (DMSO-d6, 300 MHz): d 3.64 (m, 2H, H-60,600), 4.18
(m, 2H, H-40,50), 4.29 (m, 2H, H-20,30), 5.14 (s, 2H, CH2), 5.88
(s, 1H, thiazole H-5), 7.18 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.52 (m,
4H, ArAH), 7.55 (d, 1H, J ¼ 7.8 Hz, H-10), 7.59 (s, 1H,
CH¼¼N), 7.64 (m, 4H, ArAH, pyrazole H-3), 7.75 (d, 2H, J ¼
8.5 Hz, ArAH), 7.81 (m, 2H, ArAH), 7.86 (m, 4H, ArAH),
7.97 (d, 2H, J ¼ 8.2 Hz, ArAH), 10.18 (s, 1H, NH); ms m/z
(%): 731 (Mþ, 7). Anal. Calcd. for C39H37N7O6S: C, 64.01; H,
5.10; N, 13.40. Found: C, 63.95; H, 5.02; N, 13.32%.
2,3,4,5,6-Penta-O-acetyl-D-mannose-2-{2-[[(3-(biphenyl-3-yl)-
1-phenyl-1H-pyrazol-4-yl]methylene)-hydrazono]-4-phenylthia-
zol-3(2H)-yl}acꢀetohydrazone (17). White solid 0.85 g (90%),
m.p. 149-150 C; ir (KBr) m: 1742 (C¼¼O), 1661 (C¼¼O), 1610
cmꢁ1 (C¼¼N); 1H NMR (DMSO-d6, 300 MHz): d 1.92, 1.94,
1,97, 2.02, 2.05 (5s, 15H, 5CH3), 3.89 (dd, 1H, J ¼ 11.4 Hz, J
¼ 2.8 Hz, H-60), 4.21 (m, 1H, H-600), 4.25 (m, 1H, H-50), 4.75
(t, 1H, J ¼ 9.3 Hz, H-40), 4.88 (dd, 1H, J ¼ 9.6 Hz, J ¼ 9.3
Hz, H-30), 5.15 (t, 1H, J ¼ 9.6 Hz, H-20), 5.24 (s, 2H, CH2),
5.87 (s, 1H, thiazole H-5), 7.21 (d, 2H, J ¼ 8.5 Hz, ArAH),
7.51 (m, 4H, ArAH), 7.55 (d, 1H, J ¼ 7.8 Hz, H-10), 7.60 (s,
1H, CH¼¼N), 7.68 (m, 4H, ArAH, pyrazole H-3), 7.70 (d, 2H,
J ¼ 8.5 Hz, ArAH), 7.82 (m, 2H, ArAH), 7.88 (m, 4H,
ArAH), 7.99 (d, 2H, J ¼ 8.2 Hz, ArAH), 10.29 (s, 1H, NH);
ms m/z (%): 941 (Mþ, 11). ms m/z (%) 941 (Mþ, 12). Anal.
Calcd. for C49H47N7O11S: C, 62.48; H, 5.03; N, 10.41. Found:
C, 61.38; H, 4.90; N, 10.17%.
D-Mannose 2-{2-[[(3-(biphenyl-3-yl)-1-phenyl-1H-pyrazol-
4-yl]methyl-ene)hydrazono]-4-phenylthiazol-3(2H)-yl}acetohy-
drazone (14). Yellow solid 6.58 g, (90%), m.p. 211–212ꢀC; ir
(KBr) m: 3387–3341 (OH), 1667 (C¼¼O), 1610 (C¼¼N) cmꢁ1
;
1H NMR (DMSO-d6, 300 MHz): d 3.66 (m, 2H, H-60,600), 4.19
(m, 2H, H-40,50), 4.29 (m, 2H, H-20,30), 5.16 (s, 2H, CH2),
5.18 (s, 2H, CH2), 5.89 (s, 1H, thiazole H-50), 7.21 (d, 2H, J
¼ 8.5 Hz, ArAH), 7.51 (m, 4H, ArAH), 7.54 (d, 1H, J ¼ 7.8
Hz, H-10), 7.59 (s, 1H, CH¼¼N), 7.64 (m, 4H, ArAH, pyrazole
H-3), 7.59 (s, 1H, CH¼¼N), 7.65 (m, 4H, ArAH, pyrazole H-
3), 7.72 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.80 (m, 2H, ArAH),
7.86 (m, 4H, ArAH), 7.96 (d, 2H, J ¼ 8.2 Hz, ArAH), 10.17
(s, 1H, NH); ms m/z (%): 731 (Mþ, 7). Anal. Calcd. for
C39H37N7O6S: C, 64.01; H, 5.10; N, 13.40. Found: C, 63.90;
H, 5.14; N, 13.31%.
2,3,4,5-Tetra-O-acetyl-D-xylose-2-{2-[[(3-(biphenyl-3-yl)-1-
phenyl-1H-pyrazol-4-yl]methylene)-hydrazono]-4-phenylthia-
zol-3(2H)-yl}acetohydrazone (18). Yellow solid 0.76 g (88%),
ꢀ
m.p. 152-153 C; ir (KBr) m: 1739 (C¼¼O), 1663 (C¼¼O), 1610
(C¼¼N) cmꢁ1
;
1H NMR (DMSO-d6, 300 MHz): d 1.90, 1.93,
1.98, 2.05 (4s, 12H, 4CH3), 3.88 (dd, 1H, J ¼ 11.4 Hz, J ¼
2.8 Hz, H-50), 4.18 (m, 1H, H-500), 4.75 (t, 1H, J ¼ 9.3 Hz, H-
40), 5.18 (s, 2H, CH2), 4.89 (dd, 1H, J ¼ 9.6 Hz, J ¼ 9.3 Hz,
H-30), 5.15 (t, 1H, J ¼ 9.6 Hz, H-20), 5.86 (s, 1H, thiazole H-
5), 7.21 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.52 (d, 1H, J ¼ 7.8 Hz,
H-10), 7.56 (m, 4H, ArAH), 7.60 (s, 1H, CH¼¼N), 7.64 (4H,
m, ArAH, pyrazole H-3), 7.73 (d, 2H, J ¼ 8.5 Hz, ArAH),
7.79 (m, 2H, ArAH), 7.88 (m, 4H, ArAH), 8.02 (d, 2H, J ¼
8.2 Hz, ArAH), 10.25 (s, 1H, NH); ms m/z (%): 869 (Mþ,
D-Xylose 2-{2-[[(3-(biphenyl-3-yl)-1-phenyl-1H-pyrazol-4-yl]
methylene)-hydrazono]-4-phenylthiazol-3(2H)-yl}acetohydrazone
(15). Yellow solid 5.74 g (82%), m.p. 203–200ꢀC; ir (KBr) m:
1
3412–3367 (OH), 1664 (C¼¼O), 1614 (C¼¼N) cmꢁ1; H NMR
(DMSO-d6, 300 MHz): d 3.64 (m, 2H, H-50,500), 4.18 (m, 2H,
H-40), 4.23 (m, 2H, H-20,30), 5.16 (s, 2H, CH2), 5.88 (s, 1H,
thiazole H-5), 7.25 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.51 (d, 1H, J
¼ 7.8 Hz, H-10), 7.55 (m, 4H, ArAH), 7.59 (s, 1H, CH¼¼N),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

100
A. A. Abdel-Rahman, W. A. El-Sayed, E. G. Zaki, A. A. Mohamed, and A. A. Fadda
Vol 49
12). Anal. Calcd. for C46H43N7O9S: C, 63.51; H, 4.98; N,
11.27. Found: C, 63.36; H, 4.88; N, 11.14%.
d6, 300 MHz): d 1.91, 1,98, 2.02, 2.05, 2.21 (5s, 15H, 5CH3),
3.89 (dd, 1H, J ¼ 11.4 Hz, J ¼ 2.8 Hz, H-40), 4.21 (m, 1H,
H-400), 5.21 (s, 2H, CH2), 4.93 (dd, 1H, J ¼ 9.6 Hz, J ¼ 9.3
Hz, H-30), 5.15 (t, 1H, J ¼ 9.6 Hz, H-20), 5.18 (dd, 1H, J ¼
9.6 Hz, J ¼ 7.2 Hz, H-10), 5.72 (d, 1H, J ¼ 9.8 Hz, oxadizo-
line-H), 5.88 (s, 1H, thiazole H-5), 7.22 (d, 2H, J ¼ 8.5 Hz,
ArAH), 7.56 (m, 4H, ArAH), 7.61 (s, 1H, CH¼¼N), 7.66 (m,
4H, ArAH, pyrazole H-3), 7.72 (2H, d, J ¼ 8.5 Hz, ArAH),
7.80 (2H, m, ArAH), 7.86 (4H, m, ArAH), 7.98 (2H, d, J ¼
8.2 Hz, ArAH); 13C NMR (CDCl3, 75 MHz): d 20.12, 20.51,
20.59, 20.67, 29.64 (5CH3), 46.72 (CH2), 62.95 (C-40), 69.41
(C-30), 69.74 (C-20), 71.21 (C-10), 90.49 (oxadiazoline C-2),
106.69 (thiazole C-5), 123.80-144.50 (ArAC, pyrazole C-4,5),
152.41, 153.53, 154.15, 156.29, 157.19 (4C¼¼N, thiazole C-4),
169.18, 169.73, 170.19, 170.45, 171.37 (5CO). ms m/z (%)
984: (Mþ, 11). ms m/z (%): 911 (Mþ, 11). Anal. Calcd. for
C48H45N7O10S: C, 63.22; H, 4.79; N, 10.75. Found: C, 63.10;
H, 4.61; N, 10.62%.
Antimicrobial activity. The target compounds were
screened in vitro for their antimicrobial activities against Esch-
erichia coli NRRL B-210 (Gram -ve bacteria), Bacillus subtilis
NRRL B-543 and Staphylococcus aureus (Gram þve bacteria),
Aspergillus niger and Candida albicans NRRL Y-477 (Fungi).
These microorganisms were obtained from Northern Utiliza-
tion Research and Development Division, U.S. Department of
Agricultural Peoria, Illinois.
The agar diffusion method [46] was used for this purpose.
The bacteria and fungi were maintained on nutrient agar and
Czapek’s-Dox agar media, respectively. The assay medium
flasks containing 50mL of nutrient agar for bacteria and Cza-
pek’s-Dox agar medium for fungi respectively were allowed to
reach 40–50ꢀC to be inoculated with 0.5 mL of the test orga-
nism cell suspension.
The flasks were mixed well and poured each into a Petri
dish (15 x 2 cm) and allowed to solidify. After solidification,
holes (0.6 cm diameter) were made in the agar plate by the
aid of a sterile cork poorer (diameter 6 mm). Target com-
pounds were dissolved each in 2 mL DMSO. In these holes,
100 lL of each compound was placed using an automatic
micropipette. The Petri dishes were left at 5ꢀC for 1 h to
allow diffusion of the samples through the agar medium and
retard the growth of the test organism. Plates were incubated
at 30ꢀC for 24 h for bacteria and 72 h of incubation at 28ꢀC
for fungi.
1-{5-[[2-[[[3-(Biphenyl-4-yl)-1-phenyl-1H-pyrazol-4-yl]methyl-
ene]hydrazono]-4-phenylthiazol-3(2H)-yl]methyl]-2-(O-acetyl-
sugar)-1,3,4-oxadiazol-3(2H)-yl}ethanones (19–21). General
procedure. A solution of the sugar hydrazones 13–15, (1
mmol) in acetic anhydride (5 mL) was boiled under reflux for
1 h. The resulting solution was poured onto crushed ice, and
the product that separated out was filtered off, washed with a
saturated solution of sodium hydrogen carbonate followed by
water and then dried.
1-{5-[[2-[[[3-(Biphenyl-4-yl)-1-phenyl-1H-pyrazol-4-yl]methy-
lene]-hydrazono]-4-phenylthiazol-3(2H)-yl]methyl]-2-(1,2,3,4,5-
penta-O-acetyl-D-galactopentitolyl)-1,3,4-oxadiazol-3(2H)-yl}
ethanone (19). White foam 0.77 g (78%); ir (KBr) m: 1743
(C¼¼O), 1665 (C¼¼O), 1618 (C¼¼N) cmꢁ1; 1H NMR (DMSO-d6,
300 MHz): d 1.90, 1.93, 1.97, 2.02, 2.04, 2.22 (6s, 18H, 6CH3),
3.88 (dd, 1H, J ¼ 11.4 Hz, J ¼ 2.8 Hz, H-50), 4.22 (m, 1H, H-
500), 4.27 (m, 1H, H-40), 4.92 (dd, 1H, J ¼ 9.6 Hz, J ¼ 9.3 Hz,
H-30), 5.15 (t, 1H, J ¼ 9.6 Hz, H-20), 5.19 (s, 2H, CH2), 5.25
(dd, 1H, J ¼ 9.6 Hz, J ¼ 7.2 Hz, H-10), 5.72 (d, 1H, J ¼ 9.8 Hz,
oxadizoline-H), 5.90 (s, 1H, thiazole H-5), 7.25 (d, 2H, J ¼ 8.5
Hz, ArAH), 7.56 (m, 4H, ArAH), 7.61 (s, 1H, CH¼¼N), 7.645
(m, 4H, ArAH, pyrazole H-3), 7.71 (d, 2H, J ¼ 8.5 Hz, ArAH),
7.80 (m, 2H, ArAH), 7.88 (m, 4H, ArAH), 7.98 (d, 2H, J ¼ 8.2
Hz, ArAH); 13C NMR (CDCl3, 75 MHz): d 20.314, 20.51,
20.55, 20.68, 20.75, 29.65 (6CH3), 46.71 (CH2), 62.91 (C-50),
65.35 (C-40), 68.40 (C-30), 69.73 (C-20), 71.15 (C-10), 90.12
(oxadiazoline C-2), 107.39 (thiazole C-5), 122.80-142.47
(ArAC, pyrazole C-4,5), 152.40, 153.51, 154.14, 156.29,
157.29 (4C¼¼N, thiazole C-4), 169.14, 169.78, 170.14, 170.42,
170.77, 171.09 (6CO). ms m/z (%) 984: (Mþ, 11). ms m/z (%):
984 (Mþ, 11). Anal. Calcd. for C51H49N7O12S: C, 62.25; H,
5.02; N, 9.96. Found: C, 62.08; H, 4.95; N, 9.71%.
1-{5-[[2-[[[3-(Biphenyl-4-yl)-1-phenyl-1H-pyrazol-4-yl]methy-
lene]-hydrazono]-4-phenylthiazol-3(2H)-yl]methyl]-2-(1,2,3,4,5-
penta-O-acetyl-D-mannopentitolyl)-1,3,4-oxadiazol-3(2H)-yl}
ethanone (20). White foam 0.75 g (76%); ir (KBr) m: 1745
(C¼¼O), 1666 (C¼¼O), 1615 (C¼¼N) cmꢁ1; 1H NMR (DMSO-d6,
300 MHz): d 1.91, 1.94, 1,98, 2.02, 2.05, 2.20 (6s, 18H, 6CH3),
3.87 (dd, 1H, J ¼ 11.4 Hz, J ¼ 2.8 Hz, H-50), 4.20 (m, 1H, H-
500), 4.24 (m, 1H, H-40), 4.92 (dd, 1H, J ¼ 9.6 Hz, J ¼ 9.3 Hz, H-
30), 5.15 (t, 1H, J ¼ 9.6 Hz, H-20), 5.19 (s, 2H, CH2), 5.24 (dd,
1H, J ¼ 9.6 Hz, J ¼ 7.2 Hz, H-10), 5.71 (d, 1H, J ¼ 9.8 Hz, oxa-
dizoline-H), 5.89 (s, 1H, thiazole H-5), 7.24 (d, 2H, J ¼ 8.5 Hz,
ArAH), 7.55 (m, 4H, ArAH), 7.59 (s, 1H, CH¼¼N), 7.64 (m, 4H,
ArAH, pyrazole H-3), 7.70 (d, 2H, J ¼ 8.5 Hz, ArAH), 7.80 (m,
2H, ArAH), 7.87 (m, 4H, ArAH), 7.98 (d, 2H, J ¼ 8.2 Hz,
ArAH); 13C NMR (CDCl3, 75 MHz): d 20.14, 20.52, 20.57,
20.70, 20.75, 29.66 (6CH3), 46.75 (CH2), 62.92 (C-50), 65.35 (C-
40), 68.40 (C-30), 69.72 (C-20), 71.17 (C-10), 90.42 (oxadiazoline
C-2), 106.88 (thiazole C-5), 122.81-142.49 (ArAC, pyrazole C-
4,5), 152.41, 153.53, 154.15, 156.29, 15.15 (4C¼¼N, thiazole C-
4), 169.11, 169.78, 170.15, 170.44, 170.78, 171.36 (6CO). ms
m/z (%) 984: (Mþ, 11). Anal. Calcd. for C51H49N7O12S: C,
62.25; H, 5.02; N, 9.96. Found: C, 62.10; H, 4.94; N, 9.70%.
1-{5-[[2-[[[3-(Biphenyl-4-yl)-1-phenyl-1H-pyrazol-4-yl]methy-
lene]-hydrazono]-4-phenylthiazol-3(2H)-yl]methyl]-2-(1,2,3,4-
tetra-O-acetyl-D-xylotetritolyl)-1,3,4-oxadiazol-3(2H)-yl}etha-
none (21). White foam 0.66 g (73%); IR (KBr) m 1741
DMSO showed no inhibition zones. The diameter of the
resulted inhibition zone was measured in cm (Table 1).
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