Studies with pyrazol-3-carboxylic acid hydrazide: The synthesis of new pyrazolyloxadiazole and pyrazolyltriazole derivatives

Article abstract of DOI:10.1080/10426500600605731

A simple and versatile method for the synthesis of pyrazol-3-yl-1,3,4- oxadiazole, pyrazol-3-yl-1,2,4-triazole, (1,5-diphenylpyrazol-3-yl)-(3,5- dimethyl-1-carbonyl)pyrazole, and (1,5-diphenylpyrazol-3-yl)-(5-hydroxy-3- metheyl-1-carbonyl)pyrazole derivat

Full text of DOI:10.1080/10426500600605731

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Phosphorus, Sulfur, and Silicon
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Studies With Pyrazol-3-
Carboxylic Acid Hydrazide:
The Synthesis of New
Pyrazolyloxadiazole and
Pyrazolyltriazole Derivatives
Yehya M. Elkholy a , Korany A. Ali b & Ahmad M.
Farag b
a Department of Chemistry, Helwan University, Ain-
Helwan, Cairo, Egypt
b Department of Chemistry, Cairo University, Giza,
Egypt
Published online: 21 Sep 2006.
To cite this article: Yehya M. Elkholy , Korany A. Ali & Ahmad M. Farag (2006): Studies
With Pyrazol-3-Carboxylic Acid Hydrazide: The Synthesis of New Pyrazolyloxadiazole
and Pyrazolyltriazole Derivatives, Phosphorus, Sulfur, and Silicon and the Related
Elements, 181:9, 2037-2049
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Phosphorus, Sulfur, and Silicon, 181:2037–2049, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600605731
Studies With Pyrazol-3-Carboxylic Acid Hydrazide:
The Synthesis of New Pyrazolyloxadiazole
and Pyrazolyltriazole Derivatives
Yehya M. Elkholy
Department of Chemistry, Helwan University, Ain-Helwan, Cairo, Egypt
Korany A. Ali
Ahmad M. Farag
Department of Chemistry, Cairo University, Giza, Egypt
A
simple and versatile method for the synthesis of pyrazol-3-yl- 1,3,4-
oxadiazole, pyrazol-3-yl-1,2,4-triazole, (1,5-diphenylpyrazol-3-yl)-(3,5-dimethyl-1-
carbonyl)pyrazole, and (1,5-diphenylpyrazol-3-yl)-(5-hydroxy-3-metheyl-1-carbo-
nyl)pyrazole derivatives from 1,5-diphenylpyrazole-3-carboxylic acid hydrazide has
been developed.
Keywords 1,5-disubstituted-pyrazole-3-carboxylic acid hydrazide; pyrazolyl-1,2,4-
triazoles; pyrazolyl-1,3,4-oxadiazoles
INTRODUCTION
Many substituted 1,3,4-oxadiazoles have a wide variety of applications
as biologically active compounds in medicine and agriculture. For ex-
ample, they are used as antiperipheral vasomotility,1 a CNS stimu-
lant, antiinflammatory, hypertensive,2 hypoglycemic,3,4 analgesic, an-
ticonvulsant, antiemetic, diuretic,5 muscle relaxant,6,7 bactericidal,8
pesticidal,9 insecticidal,10 herbicidal,11,12 and fungicidal agents.13,14
On the other hand, the therapeutic effects of 1,2,4-triazoles have
been well documented.15−17 Several 1,2,4-triazole derivatives show
antinflammatory,18 vasodilators19 and psychotropic properties.20 Re-
cently, our interest in the synthesis of various substituted heterocyclic
systems, which could be adapted for the preparation of small libraries,
has been the subject of several publications from our laboratory.21−31
During our investigation, we have found that acid hydrazides can be
Received November 14, 2005; accepted December 9, 2005.
Address correspondence to Yehya M. Elkholy, Helwan University, Department of
Chemistry, Faculty of Science, Ain-Helwan, Cairo, Egypt. E-mail: y elkholy@yahoo.com
2037

2038
Y. M. Elkholy et al.
used as useful intermediates leading to the formation of several het-
erocycles of potential biological activity, such as 1,2,4-triazoles, 1,3,
4-oxadiazoles, and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines.23,32
In this context, we report a convenient route to some new pyrazolyl-
1,2,4-triazole, pyrazoly-1,3,4-oxadiazole, (1,5-diphenyl-1H-pyrazol-3-
yl)-(3,5-dimethyl-1-carbonyl) pyrazole, and (1,5-diphenyl-1H-pyrazol-
3-yl)-(5-hydroxy-3-metheyl-1-carbonyl) pyrazoles starting from a read-
ily accessible 1,5-diphenyl-1H-pyrazole-3-carboxylicacidhydrazide.
RESULTS AND DISCUSSION
The treatment of 5-aryl-3H-furan-2-ones (2a, b)33,35 (formed in situ
by the cyclization of 4-oxo-4-arylbutyric acid 1 by the action of acetic
anhydride-sulfuric acid mixture) with aromatic diazonium salts
afforded colored products that were identified as 3-arylhydrazono-
5-aryl-3H-furan-2-one derivatives (3a, b). Structures of the latter
products were confirmed by the appearance of hydrazones NH and car-
bonyl bands near 3280 and 1750 cm−1, respectively, in their IR spectra
and the lack of the characteristic signals due to methylene protons in
1
their H NMR spectra. Compounds (3a, b) were also obtained from
the reaction of intermediate 5-aryl-3H-furan-2-one derivatives (2a, b)
with N-nitrosoacylarylamine[34] in ethanol at r.t. (Scheme 1).
SCHEME 1

Studies With Pyrazol-3-Carboxylic Acid Hydrazide
2039
When 3-arylhydrazono-5-aryl-3H-furan-2-one derivatives (3a, b)
were treated with hydrazine hydrate, they afforded products identified
as the 1,5-diaryl-1H-pyrazole-3-carboxylic acid hydrazide derivatives
(4a, b), respectively (Scheme 1). Structures of the isolated products
were assigned on the basis of their elemental analysis and spectral
data. For example, IR spectra of the isolated products showed in each
case three bands in the region 3286–3210 cm−1 corresponding to the
NH and NH2 groups and a carbonyl absorption band near 1689 cm−1
.
The 1H NMR spectrum of (4a), as an example, showed a singlet signal
at δ 5.1 corresponding to 4-CH of the pyrazole ring and two broad bands
(D2O-exchangeable) at δ 4.34 and 8.73 due to NH2 and NH protons, re-
spectively, in addition to a multiple signal in the region δ 7.13–7.53 due
to aromatic protons. Moreover, the mass spectrum of the same product
revealed a peak corresponding to its molecular ion at m/z 278. The other
possible 3-aryl-5-arylhydrazono-1H-pyridazine-6-one structure (5) was
ruled out on the basis of IR and 1H NMR spectra of the reaction products
(see Experimental section).
The treatment of 1,5-diphenyl-1H-pyrazole-3-carboxylic acid
hydrazide (4a) with carbon disulphide in ethanolic potassium hydrox-
ide solution afforded the corresponding potassium N-(1,5-diphenyl-
1H-pyrazole-3-carbonyl)-hydrazinecarbo dithioate intermediate (6)
(Scheme 2). The treatment of the potassium salt (6) with hydrazine hy-
drate afforded a single product (as tested by TLC) identified as 4-amino-
3-(1,5-diphenyl-1H-pyrazol-3-yl)-1,2,4-triazole-5-thiol (7) according to
its elemental analysis and spectral data. For example, its IR spectrum
revealed an absorption band in the region 3147 cm−1 characteristic
SCHEME 2

2040
Y. M. Elkholy et al.
for a NH2 group. Its mass spectrum revealed a peak at m/z 334
corresponding to its molecular ion.
When the potassium salt (6) was heated in pyridine, it gave only
one isolable product that was identified as 5-(1,5-diphenyl-1H-pyrazol-
3-yl)-1,3,4-oxadiazole-2-thiol (8) according to its elemental analysis and
spectral data. This conclusion was further supported by the chemical
transformation of the latter product into 4-amino-3-(1,5-diphenyl-1H-
pyrazol-3-yl)-1,2,4-triazole-5-thiol (7) by a reaction with hydrazine hy-
drate (Scheme 2).
When pyrazole-3-carboxylic acid hydrazide (4a) was treated with
phenyl isothiocyanate, it afforded a single product identified as 1-(1,5-
diphenyl-1H-pyrazole-3-carbonyl)-4-phenylthiosemicarbazide (9). The
treatment of a suspension of the latter product with sodium hydrox-
ide solution, under reflux, afforded 3-(1, 5-diphenyl-1H-pyrazol-3-yl)-
4-phenyl-4H-1, 2, 4-triazole-5-thiole (10) (Scheme 3). Structures of the
isolated products were established on the basis of their elemental anal-
ysis and spectral data (see Experimental section).
SCHEME 3

Studies With Pyrazol-3-Carboxylic Acid Hydrazide
2041
The treatment of the 1,2,4-triazole-5-thiol (10) with ethanolic solu-
tion of sodium ethoxide followed by the addition of an equimolar amount
of methyl iodide afforded 3-(1,5-diphenyl-1H-pyrazol-3-yl)-4-phenyl-5-
methylthio-4H-1,2,4-triazole (12) (Scheme 3).
On the other hand, when the pyrazole-3-carboxylic acid hydrazide
(4a) was treated with a solution of potassium thiocyanate in the
presence of hydrochloric acid, it afforded 1-(1,5-diphenyl-1H-pyrazole-
3-carbonyl)thiosemicarbazide (14) (Scheme 4). The latter product
underwent an intermolecular cyclization upon treatment with sodium
hydroxide to afford a single product (TLC analysis) for which the 3-(1,5-
diphenyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-5-thiole structure (15) was
assigned. The mass spectrum of the reaction product revealed a peak at
m/z 319. This indicates that the thiosemicarbazide (14) undergoes inter-
molecular cyclization via the loss of a water molecule, which supports
the assigned structure (15) and ruled out the other possible structure
(16) (Scheme 4).
SCHEME 4
Next, when the pyrazole-3-carboxylic acid hydrazide (4a) was treated
with ethyl acetoacetate, in the presence of a catalytic amount of piper
dine, it afforded a product identified as (1,5-diphenyl-1H-pyrazol-3-
yl)-(5-hydroxy-3-metheyl-1-carbonyl)pyrazole (17) (Scheme 5). The IR
spectrum of the isolated product revealed a characteristic carbonyl ab-
sorption band at 1650 cm−1, whereas its mass spectrum revealed a peak
corresponding to its molecular ion at m/z 345.

2042
Y. M. Elkholy et al.
SCHEME 5
Similarly, the pyrazole-3-carboxylic acid hydrazide (4a) re-
acts with acetyl acetone, under the same reaction condition, to
afford the corresponding (1,5-diphenyl-1H-pyrazol-3-yl)-(3,5-dimethyl-
1-carbonyl)pyrazole (18) (Scheme 5). The structure of the latter product
was established on the basis of its elemental analysis and spectral data
(see Experimental section).
EXPERIMENTAL
All melting points were measured on a Gallenkamp melting point ap-
paratus and are uncorrected. The infrared spectra were recorded in
potassium bromide disks on a Pye Unicam SP-3-300 and Shimadzu FT
IR 8101 PC infrared spectrophotometers. NMR spectra were recorded
on a Varian Mercury VX-300 NMR spectrometer.1H spectra were run
at 300 MHz and 1H NMR spectra were run at 75.46 MHz in deuterated
chloroform (CDCl3) or dimethylsulphoxide (DMSO-d6). Chemical shifts
are quoted in δ and were related to that of the solvents. Mass spectra
were recorded on a Shimadzu GCMS-QP-1000EX mass spectrometer
at 70 e.V. Elemental analyses were carried out at the Micro-Analytical
Center of Cairo University, Egypt. 5-aryl-3H-furan-2-ones (2a, b) were
prepared according to the literature procedure.33,35
3-Arylhydrazono-5-aryl-3H-furan-2-ones 3a,b
Method A
General Procedure: The appropriate 4-oxo-4-arylbutyric acid (1) (40
mmol) was added to acetic anhydride (40 mL) containing a few drops
(0.5 mL) of sulfuric acid, and the mixture was heated on a water bath for
70 min and then allowed to cool to r.t.33 This solution was added drop-
wise with stirring to a solution of the appropriate aromatic diazonium

Studies With Pyrazol-3-Carboxylic Acid Hydrazide
2043
salt (40 mmol) at 0–5◦ C over a period of 30 min. After the complete
addition, the reaction mixture was allowed to stand overnight on a re-
frigerator, and the precipitated solid was collected by filtration, washed
with water, and finally crystallized from ethanol/DMF to afford the cor-
responding hydrazone derivatives (3a,b).
Method B
General Procedure: To the appropriate 5-aryl-3H-furan-2-one
(2)33,35 10 mmol (prepared in situ according to method A) the appro-
priate N-nitrosoacylarylamine34,35 (10 mmol) was added. The reaction
mixture was shaken to effect a complete dissolution of the reactants
and then left to stand overnight at r.t. The precipitated solid was col-
lected by filtration, washed with water, and finally crystallized from
ethanol/DMF to afford products identical in all respects (m.p., mixture
m.p., and IR spectra) with those obtained from Method A. 5-phenyl-
3-phenylhydrazono-3H-furan-2-one (3a): Yield 67%; m.p. 227–228◦C
(lit.[35] m.p. 227).
5-(4-Methylphenyl)-3-(4-methylphenylhydrazono)-
3H-furan-2-one (3b)
Yield 89%; mp 230–231◦C; IR (KBr )ν cm−1 3263 (NH), 1743 (C O); MS,
1
m/z 292 (M+), 200, 106, 93, 77. H NMR) CDCl3): δ 3.07 (s, 3H, CH3),
3.12 (s, 3H, CH3), 5.76 (s, 1H, furan-H-4), 7.17–7.61 (m, 8H, ArHs),
10.92 (s, br, D2O-exchangable 1H, NH). Calcd. for C18H16N2O2 (292.33):
C, 73.52; H, 5.52; N, 9.58. Found: C, 73.6; H, 5.5; N, 9.6.
1,5-Diaryl-1H-pyrazole-3-carboxylic Acid Hydrazides (4a,b)
General Procedure
Hydrazine hydrate (80%, 3 mL) was added to a suspension of the ap-
propriate 3-arylhydrazonofuranone derivative (3) (10 mmol) in ethanol
(20 mL), and the reaction mixture was stirred at r.t. for 1 h. The color
of the arylhydrazone derivative disappeared, and a white deposit was
formed. It was allowed to stand overnight and was poured into water,
the precipitate was collected by filtration, washed with water, and crys-
tallized from ethanol-water.
1,5 -Diphenyl-1H-pyrazole-3-carboxylic Acid Hydrazide (4a)
Yield 72%; m.p. 153◦C (lit.[35] mp 149–150◦C); IR (KBr(ν cm−1 3286
1
(NH), 3210 (NH2), 1689 (C O); H NMR (CDCl3): δ 4.34 (s, 2H, NH2),

2044
Y. M. Elkholy et al.
8.73 (s, 1H, NH); 5.1 (s, 1H, 4-CH pyrazole), 7.13–7.53 (m, 10H, ArHs);
13C NMR (DMSO-d6): δ 156.2, 148.17, 147.12,145.3, 136.56, 129.78,
129.69, 129.45, 126.33, 120.16; MS m/z 278 (M+), 187, 130, 93, 77. Calcd.
for C16H14N4O (278.31): C, 69.09; H, 5.07; N, 20.1. Found: C, 69.1; H,
5.2; N, 20.2.
1,5-Di(4-methylphenyl)-1H-pyrazole-3-carboxylic Acid
Hydrazide (4b)
Yield 83%; mp 160◦C; IR (KBr) ν cm−1 3301 (NH), 3210 (NH2), 1690
1
(C O); H NMR (DMSO-d6): δ 2.35 (s, 3H, CH3), 3.12 (s, 3H, CH3),
4.85 (s, br. D2O-exchangable, 2H, NH2), 8.78(s, 1H, NH), 6.93 (s, 1H,
4-CH pyrazole), 7.11–7.28 (m, 8H, ArHs); 13C NMR (DMSO-d6): 156.2,
148.17, 147.12, 145.3, 136.56, 129.78, 129.69, 129.45, 126.33, 120.16,
40.20, 38.52. Calcd. for C18H18N4O (306.36): C, 70.57; H, 5.92; N, 18.29.
Found: C, 70.6; H, 6.0; N, 18.3.
The Reaction of 1,5-Diphenyl-1H-pyrazole-3-carboxylic Acid
Hydrazide (4a) with Carbon Disulfide
A solution of potassium hydroxide (0.78 g, 20 mmol), in absolute ethanol
(20 mL) and the appropriate acid hydrazide (4a) (2.78 g, 10 mmol) was
treated by the addition of carbon disulfide (1.14 g, 15 mmol), and the
mixture was stirred for 16 h. It was then diluted with 20 mL of dry ether,
and the precipitated solid was filtered off, washed with 20 mL of ether,
and dried under vacuum at 65◦C to afford potassium Nꢀ-(1,5-diphenyl-
1H-pyrazole-3-carbonyl)-hydrazine carbodithioate (6). The latter salt
was obtained in a nearly quantitative yield and was used for the next
reactions without further purification. Its characteristic spectral fea-
ture: IR (K Br) ν cm−1 1658 (C O), 3363 (NH).
4-Amino-3-(1,5-diphenyl-1H-pyrazol-3-yl)-
1,2,4-triazole-5-thiol (7)
Method A
A suspension of the potassium salt (6) (3.76 g, 10 mmol), hydrazine
hydrate (20 mmol, 95%), and water (2 mL) was refluxed with stirring
for 3 h. The color of the reaction mixture changed to green, hydrogen
sulfide was evolved (lead acetate paper and odder), and a homogeneous
solution resulted. Dilution with cold water (100 mL) and acidification
with concentrated hydrochloric acid precipitated a white solid. This
product was filtered off, washed with cold water, and recrystallized

Studies With Pyrazol-3-Carboxylic Acid Hydrazide
2045
from ethanol-water to afford 4-amino-3-(1,5-diphenyl-1H-pyrazol-3-yl)-
1,2,4-triazole-5-thiol (7).
Yield 40%, mp 129◦C, IR (KBr) ν cm−1 3147 (NH2); MS m/z 334 (M+),
252, 170, 140, 115, 77; 1H NMR (CDCl3): δ 3.81 (s, br, D2O-exchangable
2H, NH2), 5.71 (s, 1H, CH pyrazole), 7.20–7.18 (m, 10H, ArHs), 13.78 (s,
br, D2O-exchangable 1H, SH). Calcd. for C17H14N6S (334.44): C, 61.06;
H, 4.22; N, 25.13; S, 9.59. Found: C, 61.1; H, 4.3; N, 25.3; S, 9.6.
Method B
A mixture of the pyrazolo-oxadiazole (8) (3.20 g, 10 mmole), and hy-
drazine hydrate (5 mL, 95%) in water (20 mL) was refluxed with stir-
ring for 4 h, diluted with cold water (200 mL), acidified by the dropwise
addition of concentrated hydrochloric acid, and filtered off. The solid
that formed was washed with the least amount of cold water and re-
crystallization from ethanol-water (1:1). The spectra of pyrazolotriazole
obtained by this route were superimposed on those for the same sub-
stance obtained by Method A.
5-(1,5-Diphenyl-1H-pyrazol-3-yl)-1,3,4-oxadiazole-2-thiole (8)
Method A
To a solution of the hydrazide (4a) (2.78 g, 10 mmol) in ethanol (10
mL), a solution of carbon disulphide (1.14 g, 15 mmol) in water (3 mL)
and potassium hydroxide (1 g) was added, and the mixture was refluxed
until the evaluation of H2S ceased (7–8 h). The reaction mixture was
allowed to cool and then acidified with dilute hydrochloric acid. The
solid that was obtained was collected by filtration, washed with the
least amount of water, and recrystallized from ethanol-water (1:1).
Method B
A mixture of the potassium salt (6) (3.76 g, 10 mmol) and a solution
of potassium hydroxide solution (50 mL, 20%) was refluxed for 2 h,
allowed to cool, and acidified with concentrated hydrochloric acid. The
precipitate that formed was collected by filtration and washed with cold
water and recrystallization from ethanol-water (1:1).
1
Yield 50%; mp 110◦C; IR (KBr) ν cm−1 1600 (C N), 2650 (SH); H
NMR (DMSO–d6): δ 6.66 (s, 1H, pyrazole-4-H), 7.11–7.42 (m, 10H,
ArHs), 12.71 (s, 1H, SH); 13C NMR (DMSO-d6): δ148.02, 147.42, 145.81,
139.42, 136.95, 129.95, 129.88, 129.80, 129.62, 129.44, 129.36, 129.21,
129.97, 129.70, 126.36; MS m/z 320 (M+), 278, 187, 130, 93, 77. Calcd.
for C17H12N4OS (320.37): C, 63.73; H, 3.77; N, 17.48; S, 9.99. Found: C,
63.7; H, 3.8; N, 17.5; S, 10.0.

2046
Y. M. Elkholy et al.
1-(1,5-Diphenyl-1H-pyrazole-3-carbonyl)-
4-phenylthiosemicarbazide (9)
A mixture of an equimolecular quantity of the pyrazole acid hydrazide
(4a) (2.78 g, 10 mmol) and phenyl isothiocyanate (10 mmol), in absolute
ethanol (40 mL), was refluxed for 6 h. On cooling to r.t., fine crystals
deposited that were filtered off and recrystallized from ethanol.
Yield 75%; mp 198◦C; IR (KBr) ν cm−1 3310, 3201 (NH, NH), 1658
1
(C O); H NMR (DMSO-d6): δ 6.8 (s, 1H, CH-pyrazole), 7.12–7.51 (m,
15H, ArHs), 9.6 (s, br, D2O–exchangable, 2H, 2NH), 10.5(s, br. D2O-
exchangable, 1H, NH). Calcd. for C23H19N5OS (413.50): C, 66.81; H,
4.63; N, 16.94; S, 7.75. Found: C, 66.8; H, 4.7; N, 17.0; S, 7.7.
3-(1,5-Diphenyl-1H-pyrazol-3-yl)-4-phenyl-4H-1,2,4-triazole-5-
thiole (10)
A suspension of the thiosemicarbazide (9) (2.07, 5 mmol) in sodium
hydroxide solution (25 mL, 5%) was heated under reflux for 1 h. The
reaction mixture was allowed to cool and then adjusted to pH 6 with 10%
hydrochloric acid. The precipitate that formed was filtered off, washed
with water, dried, and finally recrystallized from ethanol.
Yield 83%; mp 210◦C; IR (KBr) ν cm−1 1589 (C N), 1496 (C C), 2650
(SH);1H NMR (DMSO-d6): δ 6.61 (s, 1H, CH-pyrazole), 6.99–7.54 (m,
15H, ArHs), 14.10 (s, br, D2O-exchangable, 1H, SH). MS m/z 395 (M+),
246, 198, 149, 116, 77. Calcd. for C23H17N5S (395.49): C, 69.85; H, 4.33;
N, 17.71; S, 8.11. Found: C, 69.9; H, 4.4; N, 17.8; S, 8.2.
3-(1,5-Diphenyl-1H-pyrazol-3-yl)-4-phenyl-5-methylthio-4H-
1,2,4-triazole (12)
The mercaptotriazole (10) (0.4 g, 1 mmol) was dissolved in an ethanolic
solution of sodium ethoxide [prepared from sodium metal (0.023 g, 1
mg atom) in ethanol (15 mL)]; then methyl iodide (0.3 gm, 2 mmol) was
added gradually to the resulting solution. The reaction mixture was
heated under reflux for 2 h, concentrated, cooled, diluted with water,
and left overnight. The precipitate that obtained was filtered off, washed
with water, and recrystallized from ethanol.
Yield 65%; mp 149◦C; IR (KBr) ν cm−1 1600 (C N), 1498 (C C).1H
NMR (CDCl3): δ 2.7 (s, 3H, CH3), 4.8 (s, 1H, CH), 6.9–7.35 (m, 15H,
ArH’s). Calcd. for C24H19N5S (409.45): C, 70.40; H, 4.68; N, 17.10; S,
7.83. Found: C, 70.9; H, 4.7; N, 17.2; S, 7.6.

Studies With Pyrazol-3-Carboxylic Acid Hydrazide
2047
1-(1,5-Diphenyl-1H-pyrazole-3-carbonyl) thiosemicarba-
zide (14)
To a solution of the hydrazide (4a) (2.78 g, 10 mmol) in methanol (50
mL), a solution of potassium thiocyanate (20 mmol) and hydrochloric
acid (3 mL) was added with constant stirring. The mixture was im-
mediately evaporated to dryness on a steam bath and heated for an
additional hour with another 50 mL of methanol. The resulting solid
was treated with water and with little ethanol and finally recrystallized
from ethanol.
Yield 75%; mp 150◦C, IR (KBr) ν cm−1 3310 (NH,NH), 3250 (NH2),
1681 (C O); 1H-NMR (CDCl3): δ 2.81 (s, br, 2H, NH2), 5.51 (s, 1H, CH
pyrazole), 6.63 (s, 1H, NH), 7.05–7.37 (m, 10H, ArHs), 9.21 (s, br, 1H,
NH). Calcd. for C17H15N5OS (337.40): C, 60.52; H, 4.98; N, 20.76, S,
9.50. Found: C, 60.6; H, 5.0; N, 20.8; S, 9.6.
3(1,5-Diphenyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-5-thiole (15)
A suspension of the thiosemicarbazid derivative (14) (0.34 g, 1 mmol)
in sodium hydroxide solution (10 mL, 10%) was heated under reflux for
1 h. The reaction mixture was allowed to cool and then adjusted to pH
6 with 10% hydrochloric acid. The precipitate that formed was filtered
off, washed with water, dried, and recrystallized from ethanol.
Yield 78%; mp 173◦C; IR (KBr) ν cm−1 1598 (C N);1H NMR (DMSO-
d6)): δ 6.9 (s, 1H, CH-pyrazole), 7.05–7.47(m, 10H, ArHs), 13.7 (s, 1H,
NH), 13.8 (s, 1H, SH). MS m/z 319 (M+), 264, 246, 116, 77, 51. Calcd.
for C17H13N5S (319.40): C, 63.93; H, 4.10; N, 21.92; S, 10.04. Found: C,
64.0; H, 4.2; N, 22.0; S, 10.0.
(1,5-Diphenyl-1H-pyrazol-3-yl)-(5-hydroxy-3-metheyl-1-
carbonyl)pyrazole (17)
To a mixture of 1,5-diphenylpyrazol-3-carboxylic acid hydrazide (4a)
(2.78 g, 10 mmol) and ethyl acetoacetate (10 mmol) in ethanol (20 mL),
piperdine (0.4 mL) catalysis (basic medium) was added, and the mix-
ture was refluxed for 10 h. The precipitated solid was filtered off and
recrystallized from dilute ethanol 95%.
Yield 42%; mp 166◦C IR (KBr) ν cm−1 1695 (C O). MS m/z 344 (M+),
1
303, 264, 247, 105, 77. H-NMR (CDCl3): δ 1.68 (s, 3H, CH3), 4.48 (s,
1H, 4-H pyrazole), 5.4 (s, 1H, CH pyrazole), 7.09–7.59 (m, 10H, ArH’s),
10.8 (s, br, D2O-exchangeable 1H, OH). Calcd. for C20H16N4O2 (344.37):
C, 69.75; H, 4.68; N, 16.27. Found: C, 69.8; H, 4.7; N, 16.3.

2048
Y. M. Elkholy et al.
(1,5-Diphenyl-1H-pyrazol-3-yl)-(3,5-dimethyl-1-
carbonyl)pyrazole (18)
To a mixture of 1,5-diphenylpyrazol-3yl-carboxylic acid hydrazide (4a)
(2.78 g, 10 mmol) and acetylacetone (10 mmol) in ethanol (20 mL),
piperidine (0.4 mL) was added, and the mixture was refluxed for 8 h.
The precipitated solid was filtered off and recrystallized from dilute
ethanol.
Yield 43%; mp 130◦C; IR (KBr) ν cm−1 1676 (C O); MS m/z 342 (M+),
266, 247, 219, 171, 116, 77, 51. Calcd. for C21H18N4O (342.40): C, 73.66;
H, 5.30; N, 16.36. Found: C, 73.6; H, 5.3; N, 16.4.
CONCLUSION
A
simple method for the synthesis of some new pyrazol-3
-yl-1,3,4-oxadiazole, pyrazol-3-yl-1,2,4-triazole, (1,5-diphenylpyrazol-3-
yl)-(3,5-dimethyl-1-carbonyl) pyrazole, and (1,5-diphenylpyrazol-3-yl)-
(5-hydroxy-3-metheyl-1-carbonyl)pyrazole derivatives of potential bio-
logical activity has been developed.
REFERENCES
[1] C. Derappe, R. Rips, O. Albert, and M. Aurousseau, Chim. Ther., 3, 181 (1968). Chem.
Abstr. 69, 106626y (1968).
[2] A. A. Deshmukh, P. B. Sattur, and U. K. Sheth, Indian. J. Exp. Biol., 4, 166 (1976).
´
[3] J. B. O Neal, H. Rosen, P. B. Russel, A. C. Adams, and A. Blumenthal, J. Med. Pharm.
Chem., 5, 617 (1962). Chem. Abstr., 57, 9168c (1962).
[4] F. Kurzer, Org. Compd. Sulphur, Selenium, Tellurium, 4, 417 (1974).
[5] J. Thomas, Ger. Pat. 2, 403, 357 (1974); Chem. Abstr., 81, 136153g (1974).
[6] H. L. Yale and K. Losee, J. Med. Chem., 9, 478–483 (1966).
[7] S. Turner, Reckitt and Colman Products Ltd., Ger. Pat. 2, 727,146 (1978); Chem.
Abstr., 88, 105357, (1978).
[8] I. Chiyomaru, K. Takita, and H. Ito, Kumiai Chem. Ind. Co. Ltd., Jap. Pat. 72; 07,
549 (1972); Chem. Abstr., 77, 549 (1972).
[9] K. Hiroshi, H. Isaq, and O. Shigeki, Zassokenkyn ,8, 46 (1969); Chem. Abstr., 73,
108544b (1970).
[10] A. K. Sen Gupta, M. Garg, and U. Chandra, J. Indian Chem. Soc., 56, 1230 (1979).
[11] Hodogaya Chemical Co. Ltd., Jap. Pat. 1980, 80 27,024; Chem. Abstr., 93, 232719q
(1980).
[12] Hakko Chem. Ind. Co. Ltd., Brit. Pat. 1,266,542 (1972); Chem. Abstr.77, 5474g
(1972).
[13] H. Singh, and L. D. S. Yadav, Agric. Biol. Chem., 40, 759 (1976).
[14] T. Misato, K. Ko, Y. Honma, K. Konno, and E. Taniyama, Inst. Phys. Chem. Res. Jap.
Pat. 772 508 (1977); Chem. Abstr. 87, 147054 (1977).
[15] B. Tozkoparan, N. Go¨khan, G. Aktay, E. Yelilada, and M. Ertan, Eur. J. Med. Chem.,
35, 743 (2000).
[16] N. Demirbas, R. Ugurluoglu, and A. Demirbas, Bioorg Med Chem., 10, 3717 (2002).

Studies With Pyrazol-3-Carboxylic Acid Hydrazide
2049
[17] G. Turan-Zitouni, M. Sıvacı, F. S. Kelıc¸, and K. Erol, Eur. J. Med. Chem., 36, 685
(2001).
[18] M. Tandon, J. P. Bartwal, T. N. Bahalla, and K. P. Bhargava, Indian J. Chem., 20,
1017 (1981).
[19] E. Tenor, and R. Ludwig, Pharmazie, 534, (1971).
[20] A. Baiocchi, A. Chiari A. Frigerio, and P. Ridolfi, Arzneim-Forsch, 400 (1973).
[21] K. M. Dawood, A. M. Farag, and H. A. Abdelaziz, J. Chem. Res., 378 (2005).
[22] Y. M. Elkholy, Heterocyclic Commun., 11, 89 (2005).
[23] K. M. Dawood, A. M. Farag, and H. A. Abdelaziz, Heteroatom Chem. 16, (2005).
[24] A. M. Farag, K. M. Dawood, and H. A. Elmenoufy Heteroatom Chem., 15, 508 (2004).
[25] A. M. Farag, K. M. Dawood, and H. A. Abdel-Aziz, J. Chem. Res., 808 (2004).
[26] K. M. Dawood, E. A. Ragab, and A. M. Farag, J. Chem. Res., (S), 685, 1151 (2003).
[27] K. M. Dawood, M. A. Raslan, and A. M., Farag, Synth. Commun., 33, 4095 (2003).
[28] A. Z. Elassar and Y. M. Elkholy, Heteroatom Chem., 14, 427 (2003).
[29] Z. E. Kandeel, K. M. Dawood, E. A. Ragab, and A. M. Farag, Heteroatom Chem., 13,
248 (2002).
[30] Y. M. Elkholy, Phosph., Sulfur, and Silicon., 177, 2661 (2002).
[31] K. M. Dawood, A. M. Farag, E. A. Ragab, and Z. E. Kandeel, J. Chem. Res. (S) 206,
622 (2000).
[32] P. Vainilavicius, R. Smicius, and V. Jakubkiene, Monatsch. Chem., 132, 825 (2001).
[33] A. Tsolomitis and C. Sandris, J. Heterocyclic Chem., 20, 1253 (1983).
[34] W. Hickinbottom, J. Reactions of Organic Compounds, p 336 (Wiley, New York, 1962).
[35] S. A. Khattab, A. S. Shawali, and A. M. Farag, J. Chem. Eng. Data, 22, 104 (1977).