Synthesis and antimicrobial activity of novel pyrazole derivatives

Article abstract of DOI:10.13005/ojc/350149

This work aimed to synthesis some new different heterocyclic compounds based on phenylpyrazole-4-carbaldehyde derivative (1) reacted with cyanoacetohydrazide to afford N'-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene]-2-cyanoacetohydrazide (2). I

Full text of DOI:10.13005/ojc/350149

ISSN: 0970-020 X
CODEN: OJCHEG
2019, Vol. 35, No.(1):
Pg. 391-398
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Access, Peer Reviewed Research Journal
www.orientjchem.org
Synthesis and antimicrobial activity of Novel Pyrazole Derivatives
HASSAN MOHAMMED AL-GHAMDI*
Department of Chemistry, Faculty of Science, Albaha University, Saudi Arabia.
*Corresponding author E-mail: hassan11220@gmail.com
http://dx.doi.org/10.13005/ojc/350149
(Received: October 25, 2018; Accepted: January 20, 2019)
ABSTRACT
This work aimed to synthesis some new different heterocyclic compounds based on
phenylpyrazole-4-carbaldehyde derivative (1) reacted with cyanoacetohydrazide to afford
N'-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene]-2-cyanoacetohydrazide (2). It was
cyclized by acetyl acetone, and aromatic aldehyde, respectively, to give pyrazolo-pyridone (4) and
substituted pyrazolochromene (6 and 8), respectively.Pyrazolo triazole (10) was obtained by coupling
of 1-azido-4-fluorobenzene with (2), which was diazotized by 3-(chlorodiazenyl)-4,6-dimethyl-
-1H-pyrazolo[3,4-b]pyridine to give pyrazolo pyridine derivative (11).N,N-Dimethylformamide dimethyl
acetal reacted with (2) to afford [(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene]-2-cyano-3-
(dimethylamino)-acrylohydrazide (13).The compound before compound yield substituted pyrazole-
4-carbohydrazide (15).Also, compound (2) reacted with phNCS in the presence of KOH and furnish
compound (22), which preferred over compound (20) All synthesized compounds were established
using IR, 1H-NMR. All synthesized compounds were screened for their antimicrobial activities.
Keywords: Pyrazole, Thiazole, Chromene, Pyridine and Antimicrobial activity.
INTRODUCTION
antimicrobial character16-17. As well as, when
introducing pyrazole and thiazole fragments to parent
pyrazol were enhancement antimicrobial power18-21
.
Pyrazolos have attracted considerable
attention for many researchers, due to their broad
effects in many different fields1-2, as agrochemicals3-4,
antimicrobial5, antifungal6, anticancer7, antidiabetic8,
anti-inflammatory9, antitumor10, antiviral11, anti-HIV
activity12, and selective enzyme inhibitory activities13.
Moreover, pyrazolo-chromene derivatives were
exhibited powerful antimicrobial and antifungal
activities14-15. Also, pyrazole compounds based on
pyridone ring moiety were evaluated against their
antibacterial and antifungal activities pyrazolpyridone
derivatives exhibit a positive acceptance as
The aim of this work is design and synthesis some
a new heterocyclic compound based on pyrazole
moiety and investigate their biological evaluation as
antimicrobial activities.
MATERIALS AND METHODS
All chemicals were obtained from Sigma-
Aldrich and used without future purifications.
All melting points are uncorrected. IR spectra
(KBr) were recorded on FTIR-5300 spectrometer
This is an
Open Access article licensed under a Creative Commons Attribution-Non Commercial-Share Alike
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AL-GHAMDI., Orient. J. Chem., Vol. 35(1), 391-398 (2019)
(lmax, cm-1). The 1H-NMR spectra were recorded in
(CDCl3 & DMSO-d6) on a Brucker Ultra-Shield 850
MHz and reported in (ppm).
(NH). 1H-NMR: δ = 2.61 (s, 3H, CH3), 7.12 – 7.78
(m, 10H, Ar-H, chromene-H) 7.79 (s, 1H, CH),
10.01 (s, 1H, NH), 13.49 (s, 1H, NH chromene).M.F.
C21H16ClN5O2. Calcd: C, 62.16; H, 3.97; Cl, 8.73; N,
17.26; O, 7.88. Found: C, 62.13; H, 3.96; Cl, 8.77;
N, 17.25; O, 7.89.
Synthesis of N'-[(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)methylene]-2-cyanoaceto hydrazide (2)
A mixture of 5-chloro-3-methyl-1-phenyl-
1H-pyrazole-4-carbaldehyde (1; 0.02 mol), and
2-cyanoacetohydrazide (0.02 mol), was refluxed
in absolute ethanol (60 ml) for 5 h at 1200C. The
reaction mixture was cooled, and the solid product
was collected, dried. m.p.: 188-1900C, yield: 5.3 g
(88%), pale yellow (acetic acid).IR:1682 (CO), 2263
(CN), 3196 (NH).1H-NMR:δ = 2.55 (s, 3H, CH3), 3.85
(s, 2H, CH2), 7.26 – 7.84 (m, 5H, Ar-H), 7.84 (s, 1H,
CH), 9.60 (s, 1H, NH). M.F. C14H12ClN5O. Calcd: C,
55.73; H, 4.01; Cl, 11.75; N, 23.21; O, 5.30. Found:
C, 55.70; H, 3.38; Cl, 11.79; N, 23.26; O, 5.28.
[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)
methylene]-2-imino-6-methoxy-2H-chromene-3-
carbohydrazide (6b)
m.p.:270-272 0C, yield:0.7 g (81%), orange
(acetic acid). IR : 1695 (CO), 3055, 3239 (NH).
1H-NMR: δ = 2.71 (s, 3H, CH3), 3.98 (s, 3H, CH3
Methoxy), 7.15 – 7.59 (m, 9H , Ar-H , chromene-H)
, 8.30 (s , 1H , CH) , 9.04 (s , 1H , NH) , 11.83 (s,
1H, NH chromene-H) .M.F. C22H18ClN5O3. Calcd: C,
60.62; H, 4.16; Cl, 8.13; N, 16.08; O, 11.01. Found:
C, 60.55; H, 4.12; Cl, 8.14; N, 16.10; O, 11.04.
Synthesis of {[(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)methylene]-amino}-4,6-dimethyl-2-
oxo-1,2-dihydropyridine-3-carbonitrile (4)
This compound was prepared by a
6-bromo-[(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)methylene]-2-imino-2H-chromene-
3-carbohydrazide (6c)
m.p.: 248-2500C, yield: 0.82 g (86%),
yellow (ethanol). IR: 1681 (CO), 3213 (NH). M.F.
C21H15BrClN5O2. Calcd: C, 52.03; H, 3.12; Br, 16.48;
Cl, 7.31; N, 14.45; O, 6.61. Found: C, 51.98; H, 3.11;
Br, 16.42; Cl, 7.32; N, 14.43; O, 6.60.
modification to that previously reported method22.
A mixture of pyrazole derivative (2; 0.002 mol),
acetyl acetone (0.002 mol) in (25 ml) of absolute
ethanol and 0.2 ml of piperidine was added. The
reaction mixture was heated under reflux for 3
hours. The solid product formed after cooling was
filtered, washed with cold methanol, and dried.m.p.:
235-2370C, yield: 0.6 g (82%), yellow (benzene). IR:
1652 (C=O), 2216 (CN).1H-NMR: δ = 2.43 (s, 6H, 2
CH3), 2.58 (s, 3H, CH3), 6.09 (s, 1H, CH pyridine),
7.26 – 7.55 (m, 5H, Ar-H) and 8.94 (s, 1H, CH). M.F.
C19H16ClN5O. Calcd: C, 62.38; H, 4.41; Cl, 9.69; N,
19.15; O, 4.37. Found: C, 62.32; H, 4.37; Cl, 9.71;
N, 19.18; O, 4.35;
Synthesis of [(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)methylene]-3-imino-3H-benzo[f]
chromene-2-carbohydrazide (8)
The compound (2;0.002 mol) was cyclized
by 2-hydroxy-1-napthaldehyde (0.002 mol) in
absolute ethanol media (20 ml) with catalytic amount
of piperidine. The reaction mixture was heated
under reflux for 3 h, the solid product formed was
filtered, washed with cold methanol, and dried.m.p.:
242-2440C, yield:0.73 g (80%), pale yellow (ethanol/
benzene) IR: 1689 (CO), 3049, 3242 (NH). M.F.
C25H18ClN5O2. Calcd: C, 65.86; H, 3.98; Cl, 7.78; N,
15.36; O, 7.02. Found: C, 65.78; H, 3.94; Cl, 7.76;
N, 15.38; O, 7.01.
Reaction of pyrazole-2-cyanoacetohydrazide
with aromatic aldehyde derivatives
Compound (2; 0.002 mol) was reacted
with aromatic aldehyde derivative (0.002 mol), in
absolute ethanol (25 ml) and 0.3 ml of piperidine was
added. The reaction mixture was refluxed for 2-3 h
at 1200C. The reaction mixture was cooled, and the
solid product was collected, and dried.
Synthesis of 5-amino[(5-chloro-3-methyl-1-
phenyl-1H-pyrazol-4-yl)methylene]-1-(4-fluoro-
phenyl)-1H-1,2,3-triazole-4-carbohydrazide (10)
1-azido-4-fluorobenzene (0.001 mol) was
dissolved in absolute ethanol (20 ml). Compound
(2; 0.001 mol), in presence of 1.2 g of sodium
ethoxide was added to the reaction mixture.
Then heated under reflux for about 3 h, the solid
[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-
yl)methylene]-2-imino-2H-chromene-3-
carbohydrazide (6a)
m.p.:236-2380C, yield:0.68 g (85%), yellow
(ethanol/benzene). IR: 1688 (CO), 3053, 3296

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AL-GHAMDI., Orient. J. Chem., Vol. 35(1), 391-398 (2019)
product was filtered, washed with cold ethanol, and
dried. m.p.: 280-2820C, yield: 0.33 g (75%), white
(1,4-dioxane). IR: 1640 (CO), 3275 (NH), 3422,
4552 (NH2). 1H-NMR : δ = 2.51 (s, 3H, CH3), 6.59
(s, 2H, NH2), 6.46 – 7.71 (m , 9H , Ar-H) , 8.57 (s,
1H, CH), 11.91 (s, 1H , NH). M.F. C20H16ClFN8O.
Calcd : C, 54.74; H, 3.68; Cl, 8.08; F, 4.33; N, 25.50;
O, 3.65. Found: C, 54.69; H, 3.64; Cl, 8.10; F, 4.34;
N, 25.57; O, 3.62.
2-{2-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-
yl)methylene]hydrazinyl}-N-(4-chlorophenyl)-2-
oxoacetohydrazonoyl cyanide (12b)
m.p.:248-2500C, yield:0.35 g (81%), yellow
(benzene). IR: 1666 (CO), 2220 (CN), 3035, 3256
(NH).M.F.C20H15Cl2N7O.Calcd:C,54.56;H, 3.43;Cl,
16.10; N, 22.28; O, 3.63. Found: C, 54.59; H, 3.37;
Cl, 16.12; N, 22.30; O, 3.61.
Synthesis of [(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)methyl-ene]-2-cyano-3-(dimethylamino)
acrylohydrazide (13)
Synthesis of {2-[2-(5-chloro-3-methyl-1-phenyl-
1H-pyrazol-4-yl)methyl-ene]hydrazinyl}-N-(4,6-
dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-
oxoacetohydrazonoyl cyanide (11)
N,N-dimethylformamide dimethyl acetal
(0.001 mol) was added to pyrazole derivative
(2;0.001 mol), in xylene (15 ml).The reaction mixture
was refluxed for 4 h at 220˚C. The reaction mixture
was cooled, and the solid product was collected and
dried. m.p.: 230-2320C, yield: 0.32 g (89%), pale
yellow (1,4-dioaxne). IR: 1674 (CO), 2181 (CN),
3340 (NH). 1H-NMR: δ = 2.61 (s, 3H, CH3), 3.39 (s,
3H, CH3), 3.41 (s, 3H, CH3), 7.23– 7.93 (m, 6H, Ar-H
and CH ), 8.94 ( s, 1H, CH ), 10.00 ( s, 1H, NH ). M.
F. C17H17ClN6O. Calcd: C, 57.23; H, 4.80; Cl, 9.94;
N, 23.55; O, 4.48. Found: C, 57.16; H, 4.77; Cl, 9.90;
N, 23.60; O, 4.43.
A mixture of pyrazole derivative (2; 0.001
mol) and 3-(chlorodiazenyl)-4,6-dimethyl-1H-
pyrazolo[3,4-b]pyridine (0.001 mol), in pyridine
(15 ml) .The reaction mixture was stirred at 0˚C for
3 h, then poured into ice cold water.The solid product
was collected and dried. m.p.: 244-2460C, yield: 0.4
g (85%), green (ethanol/benzene). IR: 1652 (CO),
1
2217 (CN), 3212, 3262 .3403 (NH). H-NMR: δ =
2.70 (s, 3H, CH3), 2.92 (s, 3H, CH3), 3.18 (s, 3H,
CH3), 7.15 – 7.59 (m, 6H, Ar-H), 8.28 (s, 1H, CH),
8.28 (s, 1H, NH), 9.35 and 11.03 (s, 2H, NH). M.F.
C22H19ClN10O. Calcd: C, 55.66; H, 4.03; Cl, 7.46; N,
29.48; O, 3.37. Found: C, 55.57; H, 3.98; Cl, 7.47;
N, 29.51; O, 3.36.
Synthesis of 3-amino[(5-chloro-3-methyl-1-
phenyl-1H-pyrazol-4-yl)methylene]-1H-pyrazole-
4-carbohydrazide (15)
A mixture of (13; 0.001 mol), hydrazine
hydrate (0.001 mol), in (15 ml) of 1, 4-dioxane. The
reaction mixture was heated under reflux for 7 h, the
solid product is filtered, washed with cold ethanol,
and dried.m.p.:105-1060C, yield:0.28 g (87%) white
(ethanol). IR: 1597, 1633 (C=N), 3208, 3364 (NH2).
1H-NMR:δ = 2.56 (s, 3H, CH3), 5.40 (s, 2H, NH2) and
7.19 – 7.51 (m, 7H, Ar-H), 7.67 (s, 1H, CH) and 8.59
(s, 2H, NH). M.F. C15H14ClN7O. Calcd: C, 52.39; H,
4.08; Cl, 10,34; N, 28.53; O, 4.66. Found: C, 52.35;
H, 4.10; Cl, 10.31; N, 28.54; O, 4.62.
General procedure for Reaction of pyrazole-2-
cyanoacetohydrazide with benzenediazonium
chloride derivatives
Pyrazole derivative (2; 0.001 mol) and
1-chloro-2-phenyldiazene derivative (0.001 mol) was
dissolved in (15 ml) of pyridine.The reaction mixture
was stirred at 0˚C for 2 h and poured into ice cold
water. The solid product was collected and dried.
2-{2[-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-
4-yl) methylene]hydrazinyl}-2-oxo-N-phenyl
acetohydrazonoyl cyanide (12a)
General Procedure for [(5-chloro-3-methyl-1-
phenyl-1H-pyrazol-4-yl)methylene]-2-cyano-
2-(4-hydroxy-3-phenylthiazol-2(3H)-ylidene)-
acetohydrazi de (22)
m.p.: 196-1970C, yield: 0.35 g (87%), red
(ethanol) .IR : 1667 (CO) , 2220 (CN), 3042, 3256
(NH).1H-NMR : δ = 2.65 (s , 3H, CH3), 7.18 – 7.99
(m, 10H , Ar-H), 8.16 (s, 1H, CH), 9.17 and 14.14
(s , 2H , NH) . M.F. C20H16ClN7O. Calcd: C, 59.19; H,
3.97; Cl, 8.73; N, 24.17; O, 3.94. Found: C, 59.13;
H, 3.94; Cl, 8.75; N, 24.12; O, 3.94.
To suspension of potassium hydroxide
(0.01 mol) in dry DMF (10 ml) Pyrazole derivative
(2; 0.01 mol) was added during stirring, phenyl
isothiocyanate (0.01 mol) was dropped slowly to the
reaction mixture.After completing of addition, stirring
of the reaction mixture was continued for 5 hours.

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AL-GHAMDI., Orient. J. Chem., Vol. 35(1), 391-398 (2019)
Then treated with ethyl bromoacetate (0.01mol) and
the stirring was continued at room temperature for
4 hours. The mixture was then triturated with cold
H2O (100 ml) containing HCl (0.1 N). The resultant
solid product was collected by filtration and dried.
m.p.: 198-1990C, yield: 0.4 g (84%), red (ethanol).
IR: 1734 (CO), 2201 (CN), 3254 (NH). 1H-NMR: δ
= 2.58 (s , 3H , CH3), 4.15 (s, 2H, CH2), 7.25 – 7.55
(m, 10H , Ar-H), 8.04 (s, 1H, CH), 9.97 (s, 1H, NH)
.M.F. C23H17ClN6O2S. Calcd : C, 57.93; H, 3.59; Cl,
7.43; N, 17.62; O, 6.71; S, 6.72 . Found: C, 57.96; H,
3.54; Cl, 7.41; N, 17.64; O, 6.70; S, 6.71.
The plates were incubated in the upright position at
36oC for 24 hours.Three replicates were carried out
for each extract against each of the test organism.
Simultaneously, addition of the respective solvent
instead of dissolved compound was carried out as
negative controls. After incubation, the diameters of
the growth inhibition zones formed around the disc
were measured with transparent ruler in millimeter,
averaged and the mean values were tabulated.
Anti-fungal activity
Active inoculum for experiments were
Antimicrobial activity
prepared by transferring many loopfuls of spores
from the stock cultures to test tubes of sterile
distilled water (SDW) that were agitated and diluted
with sterile distilled water to achieve optical density
corresponding to 2.0x105 spore/ml. inoculum of
0.1% suspension was swabbed uniformly and the
inoculum was allowed to dry for 5 min then the same
procedure was followed as described above.
The standardized disc – agar diffusion
method was followed to determine the activity of
the synthesized compounds against the tested
microorganisms.
Test Organisms
Cultures of the following microorganism
were used in the test: Gram-positive bacteria:
Staphylococcus aureus (ATCC25923) and Bacillus
subtilis (ATCC6635), Gram–negative bacteria:
Escherichia coli (ATCC 25922) and Salmonella
typhimurium (ATCC 14028),Yeast:Candida albicans
(ATCC 10231) and Fungus: Aspergillus fumigatus.
Standard references
The antibiotic chloramphenicol was used
as standard reference in the case of Gram– negative
bacteria, Cephalothin was used as standard
reference in the case of Gram–positive bacteria and
cycloheximide was used as standard reference in
the case of yeasts and fungi.
Screening for the antimicrobial potential
Preparation of tested compound
The tested compounds were dissolved in
dimethyl formamide (DMF) solvent and prepared
in two concentrations; 100 and 50 mg/ml and then
10 μl of each preparation was dropped on disk of
6 mm in diameter and the concentrations became 1
and 0.5 mg/disk respectively.In the case of insoluble
compounds, the compounds were suspended in
RESULTS AND DISCUSSION
Chemistry
The starting material N'-[(5-chloro-3-
methyl-1-phenyl-1H-pyrazol-4-yl)methylene]-2-
cyanoacetohydrazide (2) was prepared via the
reaction of 5-chloro-3-methyl-1-phenyl-1H-pyrazole-
4-carbaldehyde (1) with 2-cyanoacetohydrazide as
shown in (Scheme 1).The proposed (IR) spectrum
of compound showed a prominent peak at 2263 cm-1
DMF and vortexed then processed.
Testing for anti-bacterial and yeast activity
Bacterial cultures were grown in nutrient
1
assigned for (CN). Whereas the H-NMR (CDCl3)
broth medium at 30°C. After 16 h of growth, each
microorganism, at a concentration of 108 cells/mL,
was inoculated on the surface of Mueller-Hinton
agar plates using sterile cotton swab.Subsequently,
uniform size filter paper disks (6 mm in diameter)
were impregnated by equal volume (10 μl) from the
specific concentration of dissolved compounds and
carefully placed on surface of each inoculated plate.
show signals at δ = 3.85 ppm characteristics for
-CH2- and at 9.60 ppm for NH. when Treatment of
N'-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)
methylene]-2-cyanoacetohydrazide (3) with acetyl
acetone afforded the corresponding pyrazolo-
1
pyridone (4). The H-NMR showed a signals at
δ = 2.43 ppm characteristics for two methyl and at
6.09 ppm stands for CH in pyridine.

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AL-GHAMDI., Orient. J. Chem., Vol. 35(1), 391-398 (2019)
CN
O
Moreover, coupling of (2) with 1-azido-4-
fluorobenzene in presence of sodium ethoxide as
a catalyst, which yielded the corresponding triazole
derivative (10). The formation of triazole derivative
(10) was assumed to be formed via the acyclic
intermediate (9), which then cyclized via addition
of amino group to a cyano group (Scheme 2). The
infrared (IR) spectrum revealed the disappearance of
an absorption band for a characteristic for CN group
at 2263 cm-1, in addition to appearance of absorption
band characteristics for NH2 at 3422 and 4552 cm-1.
1H-NMR showed the disappearance of signal at
3.85 ppm characteristic for -CH2- with presence of
a characteristic signal at 6.59 ppm for NH2 group,
which supported compound (10).
N
:
N
H
O
O
N
HN
O
N
Cl
N
CN
N
Cl
O
ii
N
Ph
2
Ph
3a
O
NC
NH2
i
N
O
H
CN
CN
O
CHO
Cl
N
N
N
-H2O
N
H
N
N
N
Cl
N
N
Ph
Cl
N
Ph
OH
Ph
4
1
3b
Scheme 1. Reagents and conditions: i-Ethanol, reflux 4-5 h
ii-Ethanol/pip, reflux 3 hours
However, reaction of (2) with salicaldehyde or
its derivatives in ethanol in the presence of piperidine
as a catalyst under reflux via elimination of water
was afforded the corresponding [(5-chloro-3-methyl-
1-phenyl-1H-pyrazol-4-yl)methylene]-2-imino-2H-
chromene-3-carbohydrazide derivatives (6) via the
plausible intermediate (5) as shown in (Scheme 2)
The disappearance of absorption characteristics band
for CN group at 2263 cm-1 in 2, and appearance of
characteristics for NH at band 3296 cm-1, that supported
structure (6a) . The other evidence supported (6a),
disappearance of characteristic -CH2-signal (3.85
ppm), and presence of a characteristic signal for
chromene-NH proton at 13.49 ppm.Also,The 1H-NMR
of compound (6b) revealed a characteristic signal for
CH3 of methoxy at 3.89 ppm.
N
N
O
O
F
HN
HN
N-
N+
N
N
Cl
Cl
CN
N
N
N
N
N
:
N
Ph
HN
2
i
N
HN
N
Cl
ii
N
N
9
F
N
O
HN
N
NH
N
NH
N
Cl
O
N
CN
N
N
N
N
H
Cl
Ph
11
N
N
H2N
N
N
Ph
10
F
:
HO
:
R
N
N
HN
OH
Scheme 3. Reagent and conditions: i-Ethanol/EtONa,
reflux 3 h ii-Pyridine/0oCstirrer 3 hours
N
O
HN
Cl
R
CHO
N
N
O
Cl
CN
N
N
i
As well as, reaction of 3-(chlorodiazenyl)-
4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine in pyridine
afforded (11) via elimination of hydrogen chloride. 1H-
NMR (CDCl3) spectrum of compound (11) revealed
the disappearance of characteristic for -CH2 signal
at 3.85 ppm - with appearance of characteristic new
-NH signal at 11.03 ppm.
2
5
CHO
OH
ii
O
R
:
HN
HO
:
N
N
HN
N
HN
Cl
N
O
Cl
N
N
O
N
6
6a R= H
6b R= OCH3
6c R= Br
7
Also, reaction of benzenediazonium
chloride derivative gave (12a, 12b), as shown in
(Scheme 3). The infrared (IR) spectrum showed
prominent peak at 3256 cm-1 assigned for (NH).
1H-NMR exhibited the disappearance of signal at
3.85 ppm characteristic for -CH2- with appearance
of signal at 14.14 ppm characteristic for the
new NH. Reaction of pyrazole derivative (2) with
O
HN
N
HN
N
O
Cl
N
8
Scheme 2. Reagent and conditions: i-Ethanol/pip,
reflux 2-3 h ii-Ethanol/pip, reflux 3 hours

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N,N-Dimethylformamide dimethyl acetal in xylene
N
N
O
O
was afforded[(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)methylene]-2-cyano-3-(dimethylamino)-
acrylohydrazide (13) via elimination of two methanol
molecules.1H-NMR (CDCl3) spectrum of compound
(13) revealed the disappearance of signal at 3.85
ppm characteristic for -CH2- with absorption signal
at 7.23 ppm characteristic for CH.
K+
HN
S
C
Ph
N
HN
S- K+
KOH
-H2O
N
N
2
Cl
CH
Cl
N
N
NC
NC
17
N
Ph
Ph
Ph
16
O
N
O
EtO
NC
EtO
Br
NH
+K -
Ph
S
CH
N
O
Cl
S
Ph
N
- KBr
CN
NH
NH
N
Ph
Ph
N
18
R
NH
N
Cl
N
O
O
N
O
ii
O
HN
19
O
S
HN
N
N
NH
R
N
Cl
EtO
NC
O
N
O
N
N
Cl
CN
NC
HN
N
N2Cl
i
-EtOH
Ph
N
CN
Cl
S
2
N
N
O
NH
N
N
12
12a R = H
Ph
NH2
HN
N
Ph
N
Ph
OEt
O
N
13
Cl
NH
N
N
Cl
O
O
S
12b R = Cl
22
Ph
HN
Ph
21
20
iii
NH2NH2
Scheme 5. Reagent and conditions: i-DMF/KOH, stirrer
48 h ii-DMF, stirrer r.t 6 h iii-DMF, stirrer r.t 4 hours
N
O
N
O
HN
NH2
spectral data, an elimination of hydrogen bromide
and ethyl alcohol the most plausible mechanistic
pathway for prepared compound (22) preferred
over compound (20). the proposed mechanism
was supported by intense absorption nitrile group
band at 2201 cm-1 in IR spectrum , which would be
disappeared of compound (20) formed . Whereas
HN
N
Cl
N
N
Cl
N
N
N
N
H
:
HN
NH2
15
14
Scheme 4. Reagent and conditions: i-Pyridine/0oC, stirrer
2 h ii-Xylene, reflux 4 h iii-1,4-Dioxane, reflux 7hours
1
the HNMR spectrum showed no peaks for the
characteristics signals of ethyl protons.
The reaction of (13) with hydrazine hydrate
in 1,4-dioxane resulted in formation of 3-amino[(5-
chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene]-
1H-pyrazole-4-carbohydrazide (15) via elimination
of dimethylamine, then a cycloaddition reaction,
which led to final product, as shown on (Scheme
4). The infrared (IR) spectrum showed presence of
characteristics for NH2 bands at 3208, 3364 cm-1.
Biological activity
Agar diffusion method used for evolution
antimicrobial potency for tested compounds, using
the following microorganism:“Gram- positive bacteria:
Staphylococcus aureus (ATCC25923) and Bacillus
subtilis (ATCC6635), Gram–negative bacteria:
Escherichia coli (ATCC 25922) and Salmonella
typhimurium (ATCC 14028),Yeast:Candida albicans
(ATCC 10231) and Fungus: Aspergillus fumigatus”.
From Table 1, the compounds 6b, 6c, 8, 12a, 13 and
were found to be inactive against all microorganisms
while compounds 2, 3, 6a, 12b and 22 exhibited
moderate activity against some microorganisms only
and inactive against others. From the study, of the
biological activity of these compounds were found
that these compounds containing the unit of pyrazole
weak or no effect on microbes.
Compound (2) reacted with phenyl
isothiocyanate in presence of potassium hydroxide
afforded an intermediate product of potassium
–{2-[-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-
4-yl)methylene] hydrazinyl}-2-cyano-3-oxo-1-
(phenylamino)prop-1-ene-1-thiolate (16), which,
reacted with ethyl bromoacetate at room temperature
to give [(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)
methylene]-2-cyano-2-(4-hydroxy-3-phenylthiazol-
2(3H)-ylidene)acetohydrazide (22) as showed in
(Scheme 5).It can concluded that from the obtained

397
AL-GHAMDI., Orient. J. Chem., Vol. 35(1), 391-398 (2019)
CONCLUSION
In this work, we prepared pyrazolo-
cyanoacetohydrazide derivative (2) as a new
stating material Pyrazolo-pyridone (4), pyrazolo-
cheomene (6) and pyrazolo-benzochromene (8)
was synthesized via nucleophilic cycloaddition
reactions. when substituted aromatic azide was
reacted with (2), to give 5-aminotriazole through
dipolar cycloaddition reaction mechanism. While,
substitution reaction of (2) with diazonium chloride
salts afforded (11) and (12).The compound (2) was
reacted with phenylisothiocyanate in base medium
followed by addition of ethyl bromoacetate afforded
the pyrazolothiazole derivative (22). Antimicrobial
activity was evaluated for all synthesized compounds
the compounds 6b, 6c, 8, 12a, 13 were exhibited
inactive potency against all microorganisms while
compounds 2, 3, 6a, 12b and 22 were exhibited
moderate activity against some microorganisms
Finally, we concluded that, the newly synthesized
compounds possess a weak or no effect on
microorganisms.
ACKNOwLEDGMENT
The author would like to thank everyone
who helped in the success of this work.
Conflict Of Interest
The author declare no conflict of interest.
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