Synthesis of new heterocyclic nitrogen system bearing thiazolopyrazole moiety as new biocidal agents

Article abstract of DOI:10.14233/ajchem.2017.20732

Novel heteropolycyclic nitrogen systems as pyrazoles, phthalazines and 1,2,4-triazines bearing a thiazolopyrazole moiety (4-11) have been synthesized via heterocyclization of 2-hydrazino-thiazolo[5,4-d]pyrazole (3) with α,β-bifunctional compounds under different conditions. Structures of the new products established by their elemental analysis and spectral data. Some of these products exhibit moderate-good antibacterial activity towards E. coli and S. aureus in compare with streptomycin and tetracycline antibiotic.

Full text of DOI:10.14233/ajchem.2017.20732

Asian Journal of Chemistry; Vol. 29, No. 11 (2017), 2441-2445
ASIAN JOURNAL OF CHEMISTRY
https://doi.org/10.14233/ajchem.2017.20732
Synthesis of New Heterocyclic Nitrogen System Bearing
Thiazolopyrazole Moiety as New Biocidal Agents
*
L.A. TAIB and R.M. AL-YAMANI
Chemistry Department, Faculty of Science, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
*Corresponding author: Tel: +966 555578140; E-mail: laylataib@yahoo.com
Received: 26 April 2017;
Accepted: 25 July 2017;
Published online: 29 September 2017;
AJC-18567
Novel heteropolycyclic nitrogen systems as pyrazoles, phthalazines and 1,2,4-triazines bearing a thiazolopyrazole moiety (4-11) have
been synthesized via heterocyclization of 2-hydrazino-thiazolo[5,4-d]pyrazole (3) with α,β-bifunctional compounds under different
conditions. Structures of the new products established by their elemental analysis and spectral data. Some of these products exhibit
moderate-good antibacterial activity towards E. coli and S. aureus in compare with streptomycin and tetracycline antibiotic.
Keywords: Synthesis, Heterocyclic, Thiazolopyrazoles, Bactericidal agents.
g, 0.01 mol) in ethanol (100 mL) with piperidine (few drops)
refluxed for 8 h. After cooling the reaction mixture poured onto
ice-dilute HCl. The solid produced filtered off and crystallized
from AcOH to give compound 2, yield (2.35g, 82 %): m.p.
295-296 °C. IR (KBr, νmax, cm–1): 3500-3400 (phenolic OH),
3200 (NH), 1690 (C=O), 1600 (CH=CH), 1320 (NCS), 1190
INTRODUCTION
Rhodanine and its derivatives exhibit a wide spectrum in
the medicinal, pharmacological, agricultural and also as solar
cell applications [1,2]. In addition, arylidene rhodanine, use
for removal of Cu(II), Hg(II) and CN– ions in the industrial
wastewater [3]. On the other hand, pyrazoles showed a very
important medicinal and pharmacological properties [4].
Various heterocyclic nitrogen systems such as phathalazine
[5] and 1,2,4-triazine derivatives reported as antimicrobial,
anti HIV, anticancer and molluscicidal agents against snail [6-
10]. Upon these observations, the present work tends to
combination of these heterocyclic in one novel systems in view
of their antibacterial in the compare with antibiotics.
1
(C=S), 900-850 (substituted aryl). H NMR (DMSO-d6) δ
(ppm): 4 (1H, methine), 8-7.6 (m, 6H, aromatic H), 8.8 (1H,
α-C2-H), 10.8 (s, 1H, OH). 13C NMR (DMSO-d6) δ (ppm): 180
(C=S), 168 (C=O), 145 (C=C), 130-120 (aromatic carbons).
Analytical data for C14H9NO2S2 (287), Calcd.: C, 58.53; H,
3.13; N, 4.87; S, 22.29 %. Found: C, 58.27; H, 3.11; N, 4.55;
S, 22.0 %.
2-Hydrazino-7H-6-(2′-hydroxynaphthalen)thiazolo-
[5,4-d]pyrazole (3):A mixture of compound 2 (2.87 g, 0.01 mol)
and hydrazine hydrate (100 %, 2.5 g, 0.05 mol) in absolute
ethanol (100 mL) with piperidine (few drops) refluxed for 8 h.
Cooled then poured onto ice. The solid produced filtered off
and crystallized from EtOH, to give compound 3, yield (2.49
g, 84.3 %): m.p. 305-306 °C. UV (DMF): 410 nm. IR (KBr,
EXPERIMENTAL
Melting point were determined on Gallen-Kamp melting
point apparatus and are uncorrected. The infrared (IR) spectra
were recorded on Perkin-Elmer model RXI-IR 55529. 1H and
13C NMR spectra were recorded on a Burker DPX-400 FT
NMR spectrometer using tetramethylsilane as the internal
standard anm DMSO-d6 as solvent (chemical shift in δ, ppm).
Elemental analysis were performed on 2400 Perkin Elmer
series 2 analyzer. Direct MS spectra were carried out using
quadruple MS (Electronic ionization mod El mode with source
temperature: 200 °C) at 70 eV.
ν
max, cm–1): 3400-3100 (phenolic OH), 3350 (NH2), 3080 (NH),
1
1590 (C=N), 880-850 (substituted aryl). H NMR (DMSO-
d6) δ (ppm): 11 (s, 1H, NH), 3.5 (s, 2H, NH2), 10.5 (s, 1H, OH,
aryl), 8.8 (s, 1H, α-C5H), 7.63 (s, 1H), 7.5-7.4 (d, 2H), 7.3-7.1
(m, 2H), 7.10-7.01 (d, 2H) aromatic protons. 13C NMR (DMSO-
d6) δ (ppm): 140 (C=N), 130-120 (aromatic carbons). Analy-
tical data for C14H11N5OS(297): Calcd.: C, 56.56; H, 3.30; N,
23.56; S, 10.77 %. Found: C, 56.36; H, 3.11; N, 23.22; S,
10.55 %.
5-[(2′-Hydroxynaphthalen-1′-yl)methylene]-2-thioxo-
thiazolidin-4-one (2): A mixture of rhodanine (1) (1.33 g,
0.01 mol) and 2-hydroxynaphthalene carboxaldehyde (1.72

2442 Taib et al.
Asian J. Chem.
2-[3′,5′-Diaminopyrazol-1′-yl]-7H-6-(2′-hydroxy-
d6) δ (ppm): 148, 144, 140 (C=N), 130-125 (aromatic carbons),
68 (-CH-), 42 (CH2 carbon). Analytical data for C29H21N5SO
(487): Calcd.: C, 71.45; H, 4.31; N, 14.45; S, 6.57 %. Found:
C, 71.20; H, 4.11; N, 14.30; S, 6.25 %.
naphthalene)thiazolo[5,4-d]pyrazole (4): Equimolar mixture
of compound 3 (2.97 g, 0.01 mol) and malononitrile (0.66 g,
0.01 mol) in abs. ethanol (100 mL) with piperidine (few drops)
refluxed for 4 h. Cooled and then poured onto ice. The solid
obtained filtered off and crystallized from DMF, to give compound
4, yield (2.32 g, 78.2 %): m.p. 332-335 °C. UV (DMF): 274
nm. IR (KBr, νmax, cm–1): 3400-3300 (phenolic OH and NH2),
2-[1′,4′-Dioxo-3′-hydrophthalazin-2′-yl]-7H-6-(2′-
hydroxynaphthalene)thiazolo[5,4-d]pyrazole (8):A mixture
of compound 3 (2.97 g, 0.01 mol) and phthalic anhydride (1.48
g, 0.01 mol) in glacial acetic acid (50 mL) refluxed for 4 h.
Cooled and then poured onto ice. The solid produced filtered
off and crystallized from DMF, to give compound 8, yield
(3.46 g, 85.2 %): m.p. 341-344 °C. IR (KBr, νmax, cm–1): 3400-
3300 (phenolic OH-NH), 1680 (C=O), 1556 (C=N), 1350 (NCS),
830 (substituted aryl). 1H NMR (DMSO-d6) δ (ppm): 12.9 (s,
1H, NH), 10.55 (s, 1H, OH), 8.8 (s, 1H α-C5H), 8.20-8.02, 7.89-
7.72, 7.70-7.65, 7.55-7.22 (each d 10H, aromatic). 13C NMR
(DMSO-d6) δ (ppm): 172, 166 (2C=O), 140 (C=N), 132-122
(aromatic carbons). M/S (Int. %): 428 (0.11), 276 (3.18), 161
(25.11), 217 (18,0), 143 (100), 152 (80). Analytical data for
C22H13N5O3S (427): Calcd.: C, 61.55; H, 3.04; N, 16.39; S,
7.49 %. Found: C, 61.55; H, 2.88; N, 16.15; S, 7.29 %.
(Z)-N-((Z)-1-(4′-Chlorophenyl)-3-(7′H-6′-(2′′-hydroxy-
naphthalen)thiazolo[5,4]pyrazol-2′-yl-hydrazinyl)-3-oxo-
prop-1-en-2-yl)benzimidic acid (10):A mixture of compound
3 (2.97 g, 0.01 mol) and oxazolinone (9) (2.84 g, 0.01 mol) in
aq. EtOH (100 mL) refluxed for 1 h. Cooled and then poured
onto ice. The solid obtained filtered off and crystallized from
DMF to give compound 10, yield (4.56 g, 78.5 %): m.p. 342-
346 °C. UV (DMF): 430 nm. IR (KBr, νmax, cm–1): 3462 (phenolic
OH), 2600 (alcoholic OH), 3150 (NH), 1662 (C=O), 1620 (C=C),
1579 (C=N), 831 (substituted aryl), 679 (C-Cl). Analytical
data for C30H20N6SO3 (544): Calcd.: C, 66.17; H, 3.67; N, 15.44;
S, 5.88 %. Found: C, 65.89; H, 3.51; N, 15.30; S, 5.55 %.
2-(3′-Phenyl-6′-oxo-5′-chlorobenzylidene-1′,2′-dihydro-
1,2,4-triazin-2′-yl)-7H-6-(2′-hydroxynaphthaline)thiazolo-
[5,4-d]pyrazole (11): Compound 10 (5.8 g, 0.01 mol) with
aq. K2CO3 (10 %, 50 mL) refluxed for 2 h. Cooled and then poured
onto ice-HCl. The solid produced filtered off and crystallized
from DMF, to give compound 11, yield (4.5 g, 81 %): m.p.
355-356 °C. UV (DMF): 420 nm. IR (KBr, νmax, cm–1): 3462
(phenolic OH), 3160 (NH), 1663 (C=O), 1579 (C=N), 1320
(NSC), 831 (substituted aryl) (C-Cl). 1HNMR(DMSO-d6) δ(ppm):
11.8 (s, 1H, NH), 10.55 (s, 1H, OH), 8.9 (s, 1H, exo CH=C),
8.55 (s, 1H α-C5H), 7.9-7.66 (m, 6H, naphthyl), 7.2-6.7 (m,
4H, phenyl).Analytical data for C30H19N6O2SCl(561): Calcd.:
C, 64.17; H, 3.38; N, 14.97; S, 5.70 Cl, 6.23 %. Found: C,
64.00; H, 3.20; N, 14.71; S, 5.39 Cl, 6.00 %.
1
1594 (C=N), 1359 (NCS), 817 (substituted aryl). H NMR
(DMSO-d6) δ (ppm): 10.55 (s, 1H, OH), 8.55 (s, 1H, α-C5H),
8.1 (s, 1H, C4 of pyrazole), 3.8-3.55 (4H, 2NH2), 7.70-7.10
(m, 6H, aromatic protons). Analytical data for C17H13N7OS
(366): Calcd.: C, 56.55; H, 3.55; N, 26.77; S, 8.74 %. Found:
C, 56.32; H, 3.25; N, 26.40; S, 8.52 %.
2-[3′,5′-Dioxo-2′,3′,4′,5′-tetrahydropyrazol-1′-yl]-7H-
6-(2′-hydroxynaphthalene)-thi-azolo[5,4-d]pyrazole (5):A
mixture of compound 3 (2.97 g, 0.01 mol) and malonic acid
(1.04 g, 0.01 mol) in glacial acetic acid (50 mL) refluxed for 4 h.
Cooled and then poured onto ice. The solid obtained filtered
off and crystallized from DMF, to give compound 5, yield
(3.16 g, 86.4 %): m.p. 334-337 °C. UV (DMF): 445 nm. IR
(KBr, νmax, cm–1): 3400-3200 (phenolic OH and NH), 1700-
1670 (2C=O), 1575 (C=N), 1466 (deformation CH2), 831
(substituted aryl). 1H NMR (DMSO-d6) δ (ppm): 13.14 (s, 1H,
NH), 10.82 (s, 1H, OH), 8.14 (s, 1H, α-C5H), 7.9-7.07 (m, 6H,
aromatic protons), 3.7-3.69 (m, 2H, CH2). 13C NMR (DMSO-d6)
δ (ppm): 161 (C=O), 134 (C=N), 128-118 (aromatic carbons),
108 (C-C) 40-39.13 (CH2). M/S (Int. %) 3.66 (1.11), 276
(15.9), 217 (5.6), 143 (100), 89 (12.11), 71 (5.1), 67 (23.0).
Analytical data for C17H11N5O3S (368): Calcd.: C, 56.25; H,
2.98; N, 19.02; S, 8.69 %. Found: C, 56.01; H, 2.70; N, 18.85;
S, 8.53 %.
2-[3′-Phenyl-5′-oxo-4′,5′-dihydropyrazol-1′-yl]-7H-6-
(2′-hydroxynaphthalene)thiazolo[5,4-d]pyrazole (6): A
mixture of compound 3 (2.97g, 0.01 mol) and ethyl benzoyl
acetate (1.92 g, 0.01 mol) in absolute EtOH (50 mL) with
piperidine (few drops) refluxed for 4 h. Cooled and then poured
onto ice. The solid obtained filtered off and crystallized from
DMF to give compound 6, yield (3.6 g, 79 %): m.p. 321-324 °C.
IR (KBr, νmax, cm–1): 3300 (phenolic OH), 1682 (C=O), 1595
(C=N), 1447 (deformation CH2), 817 (substituted aryl). 1H NMR
(DMSO-d6) δ (ppm): 10.3 (s, 1H, OH), 8.2 (s, 1H, α-C5H),
7.9-7.2 (m, 6H, aryl), 7.1-6.9 (m, 4H, phenyl), 4.0 (s, 2H,
CH2-C=O). Analytical data for C23H15N5O2S(425): Calcd.: C,
64.94; H, 3.52; N, 16.47; S, 7.52 %. Found: C, 64.71; H, 3.22;
N, 16.25; S, 7.33 %.
2-[3′,5′-Diphenyl-4′,5′-dihydropyrazol-1′-yl]-7H-6-(2′-
hydroxynaphthalene)thiazolo[5,4-d]pyrazole (7):A mixture
of compound 3 (2.97 g, 0.01 mol) and benzyl benzoyl acetate
(2.54 g, 0.01 mol) in absolute EtOH (50 mL) with piperidine
(few drops) refluxed for 4 h. Cooled and then poured onto ice.
The solid produced filtered off and crystallized from DMF to
give compound 7, yield (3.7 g, 76 %): m.p. 319-322 °C. UV
(DMF): 292 nm. IR (KBr, νmax, cm–1): 3010 (aromatic CH),
2939 (aliphatic CH), 1595 (C=N), 1447 (deformation CH2),
817.83 (substituted aryl). 1H NMR (DMSO-d6) δ (ppm): 10.1
(s, 1H, OH), 8.2 (s, 1H α-C5H), 8.04-7.25 (m, 16H, aromatic),
4.59 (d, 1H, C5-pyrazole), 2.8 (m, 2H, CH2).). 13C NMR (DMSO-
Biological evaluation (antibacterial activity): Rhodanine
structure contains hydrogen bond acceptor (A), hydrogen bond
donor (D), hydrophobic (H), positive ionic center (P), negative
ionic center (N). Also, rhodanine structure characterized by a
tautomer’s generating possible stereoisomers which generating
low energy ring conformations. Thus, rhodanine and its analogues
have a various pharmacological and biological activities.Based
upon these observation, we synthesized a novel heterobicyclic
nitrogen systems starting from rhodanine (1).
In search for new antibacterial agents, the present work,
report a new synthetic of possible targets. All the synthesized
compounds were evaluated as anti-bacterial agents, against

Vol. 29, No. 11 (2017)
Synthesis of New Heterocyclic Nitrogen System Bearing Thiazolopyrazole Moiety as New Biocidal Agents 2443
Escherichia coli (Gram-negative) and Staphylococcus aureus
(Gram-positive).
O
O
HN
Piperidine
EtOH
HN
The new compounds used at different concentrations (0.1
and 0.2 %) and the examined for antibacterial activity according
to the reported method [11] (a mixture of meat extract, 5.0 g;
peptone, 5.0 g; NaCl, 5.0 g and distilled water, 1000 mL).
Streptomycin and tetracycline were used as controls for Gram-
positive and Gram-negative bacteria, respectively.
The inhibiting zone was measured by the millimeters. The
evaluation was based on the following criteria: ≥ 25 mm is
very strong; ≥ 20 mm is strong; ≥ 15 mm is medium; ≤ mm is
weak anti-bacterial activity.
S
S
S
S
1
H C
O
O
HO
NH
- H2O
S
S
HO
The results obtained, were reported in the Table-1 and
can be conclude that: (i)All the tested compounds have a degree
of biocidal activity due to presence of 2-hydroxynaphthalene
moiety (as bacterial agents). (ii) Heterocyclic systems con-
taining pyrazoleexhibited a very strong antimicrobial activity
to wards E. coli. (iii) Other tested compounds, recorded a
medium activity towards both the tested bacteria. (iv) All the
synthesized compounds showed a higher degree of activity
towards E. coli, in compare with S. aureus, which agree with
reported results.
2
EtOH/
piperidine
ex. N2H4·H2O
N
N
N
N
N
NHNH2
S
N
H
-
H2
H
NHNH2
S
H
HO
H
HO
Oxidn
3
Scheme-I: Formation of compound 3 from 1
TABLE-1
ANTIBACTERIAL ACTIVITY OF THE
SYNTHESIZED COMPOUNDS (mm)
at 4 ppm of methane protons, in addition of both NH & NH2
protons at 11 and 3.5 ppm. 13CNMR spectrum showed a lacks
of both C=S and C=C carbons.
Compd. No.
Concentration (%)
E. coli
S. aureus
0.1
0.2
0.1
0.2
0.1
0.2
0.1
0.2
0.1
0.2
0.1
0.2
0.1
0.2
18
20
30
35
27
29
16
18
18
20
14
16
12
14
16
18
26
28
22
24
15
17
16
20
16
20
25
27
4
Cyclocondensation reaction of compound 3 with 1,3-
bifunctional reagents such as malononitrile (ethanol-piperidine),
malonic acid (glacial acetic acid), ethylbenzoyl acetate (ethanol-
piperidine) and chalcone (ethanol-piperidine) via ring closure
reaction afforded 1,3,5-trisubstituted pyrazoles (4-7), respectively
(Scheme-II).
5
6
7
The structure of new compounds 4-7 has been established
upon correct elemental analysis and spectral data. UV absorption
of compound 4 showed λmax at 274 nm. While IR spectrum of
compound 5 recorded bands at ν 3287, 1700 and 1695 cm-1
NH and 2 C=O.13C NMR spectrum of compound 5 exhibited a
differ type of carbons at δ 161 (C=O), 134 (C=N), 128-118 (arom.
carbons), 108 (C-C) and 40-39.13 ppm (CH2) carbons. M/s
spectrum of compound 5 showed a molecular ion peak at 366
with m/e at 143 as base peak.
8
10
11
RESULTS AND DISCUSSION
Recently, chemistry and applications of the rhodanine
derivatives are reviewed [12,13]. Also, pyrazoles showed an
important properties in many fields [4]. In an extension of these
attempts, condensation of rhodanine (2-thioxo-thiazolidin-4-
one) (1) with 2-hydroxynaphthaliene carboxaldehyde in boiled
ethanol-piperidine yielded the arylidene (2) which on refluxed
with excess hydrazine hydrate in ethanol-piperidine produced
2-hydrazino-7H-6-(2′-hydroxyaphthalen)thiazolo[5,4-d]-
pyrazole (3) as starting material for the building of novel hetero-
polycyclic nitrogen systems as biocidal agents (Scheme-I).
Structure of compound 3 was deduced from elemental
analysis and spectral data. UV absorption recorded λmax 410
nm due to highly extention heterocyclic conjugation systems
formed. IR spectrum showed ν at 3400 and 1600 cm-1 attribute
to OH and C=N groups. 1H NMR spectrum recorded the diaster-
eotopic 1H and 2H appears as a doublet of doublets (A B system)
El-Gendy et al. [5] reported a synthesis of phthalaizin-
1,4-dione bearing various heterocyclic systems as antifungal
agents. Similarly, refluxed compound 3 with phthalicanhydride
in glacial acetic acid isolated 2-[1′,4′-dioxo-3′-hydrophthalazin-
2′-yl]-7H-6-(2′- hydroxynaphthalene)thiazolo[5,4-d]pyrazole
(8) (Scheme-III). Structure of compound 8 deduced from
elemental analyses and its spectral measurements. UV absorption
showed λmax below that of parent compound 3, which is due to
an inhibition of heteroconjugation system. IR spectrum recorded
ν at 3200-3100, 1700-1680 cm-1 for NH and C=O groups of
phthalazine, Inaddition ν at 1620-721 cm-1 for CH=CH and
C-Cl groups. M/s spectrum recorded molecular ion peak at m/z
428 with 143 as a base peak (2-hydroxynaphthalene ion).
Abdel-Rahman et al. [10] synthesized various 1,2,4-triazine
derivatives as pharmacological, medicinal and antimicrobial
agents based upon these results 2-(3′-phenyl-6′-oxo-5′-arylidene-

2444 Taib et al.
Asian J. Chem.
N
N
N
N
NHNH2
N
O
N
S
+
NHNH2
H
S
O
OH
HO
N
3
Cl
Ph
9
EtOH/
PhCOCH2COOEt
aq. EtOH
1h
3
Pipridine
EtOH/
Pipridine
CH2 (CN)2
H2N
EtOH/
Pipridine
N
N
PhCOCH=CH-Ph
O
H
N
N
NH2
N
S
N
N
N
N
Ph
OH
Cl
NH
HO
N
N
CH2 (COOH)2
N
N
Ph
S
N
4
N
S
HO
Ph
O
OH
N
10
N
N
O
N
H
7
N
S
OH
10% aq. K2 CO3
5
O
2h
N
N
N
Ph
N
N
S
OH
O
H
N
6
N
N
Scheme-II: Formation of compounds 4-7
N
Cl
N
N
S
N
N
O
HO
Ph
N
NHNH2
S
3
+
O
HO
11
Scheme-IV: Formation of compunds 10 and 11
O
3100, 1680, 1600, 700 and 3500 cm-1 for NH, C=O, C=C,
C=Cl and C=OH functional groups, respectively. 1H NMR
spectrum exhibited δ at 11.80, 10.55 8.9 and 8.55 ppm for
NH, OH, exo CH=C and α-C=H (thiazolopyrazole), respec-
tively as well as at 7.90-7.66, 7.20-6.70 ppm attribute to aromatic
protons.
CH3COOH
- H2O
O
O
H
N
N
N
Conclusion
N
N
Synthetic routes for new heterocyclic nitrogen systems
bearing thiazolopyrazole moiety derived from arylidene rhodanine
drug were developed for structure-activity relationship study.
The improved potency of these systems was possibly due to
an increase in binding interactions of hydroxyphenolic group
with an NH2 or NH residues of the tested microorganism via
the inter and/or intra H-bonding.
S
HO
8
Scheme-III: Formation of compound 8
1′H-1,2,4-triazin-2′-yl)-7H-6-(2′-hydroxynaphthaline)thiazolo-
[5,4-d]pyrazolo (11) was synthesized from the interaction
between compound 3 with oxazol-5-one (9) in aqueous ethanol
to give the acid hydrazide 10 followed by ring closure reaction
in warmed aqueous K2CO3 (Scheme-IV).
REFERENCES
1. R.M. Abdel-Rahman, Boll. Chim. Farm., 140, 401 (2001).
2. S. Kamila, H.Ankati and E.R. Biehl, Tetrahedron Lett., 52, 4375 (2011);
https://doi.org/10.1016/j.tetlet.2011.05.114.
3. M.T. Zaki, R.M. Abdel-Rahman and A.Y. El-Sayed, Anal. Chim. Acta,
307, 127 (1995);
https://doi.org/10.1016/0003-2670(95)00048-5.
Structure of compound 11 was established from elemental
analyses and its spectral data. UV absorption spectra recorded
λmax 420 nm, which attributed to new heteroconjugation system
forward. IR spectrum showed a characteristic bands at ν at
4. D.A. Bakhotmah and R.M. Abdel-Rahman, Org. Chem., 13, 62 (2016);
https://doi.org/10.2174/1570193X13666160225000114.

Vol. 29, No. 11 (2017)
Synthesis of New Heterocyclic Nitrogen System Bearing Thiazolopyrazole Moiety as New Biocidal Agents 2445
5. Z. El-Gendy, R.M. Abdel-Rahman and M.S. Abdel-Malik, Indian J.
Chem., 28B, 479 (1989).
10. R.M. Abdel-Rahman, M.S.T. Makki, T.E. Ali and M.A. Ibrahim, Eur.
J. Chem., 1, 236 (2010);
6. R.M. Abdel-Rahman and H.A. Saad, Curr. Org. Synth., 13, 408 (2016);
https://doi.org/10.2174/1570179412666150905001956.
7. R.M. Abdel-Rahman, M.S.T. Makki, T.E. Ali and M.A. Ibrahim, J.
Heterocycl. Chem., 52, 1595 (2015);
https://doi.org/10.5155/eurjchem.1.3.236-245.54.
11. N. Cong, H. Nhan, L. Van Hung, T. Thang and P.-C. Kuo, Molecules,
19, 13577 (2014);
https://doi.org/10.3390/molecules190913577.
12. T. Tomasic,A. Kovac, M. Simcic, D. Blanot, S.G. Grdadolnik, S. Gobec,
D. Kikelj and L. Peterlin Masic, Eur. J. Med. Chem., 46, 3964 (2011);
https://doi.org/10.1016/j.ejmech.2011.05.070.
13. H. Park, P.N. Chien and S.E. Ryu, Bioorg. Med. Chem. Lett., 22, 6333
(2012);
https://doi.org/10.1002/jhet.2014.
8. M.S.I. Makki, R.M. Abdel-Rahman and K.A. Khan, J. Chem., Article
ID 430573 (2014);
https://doi.org/10.1155/2014/430573.
9. R.M. Abdel-Rahman, M.S.T. Makki, T.E. Ali and M.A. Ibrahim, Curr.
Org. Synth., 10, 136 (2013);
https://doi.org/10.2174/1570179411310010006.
https://doi.org/10.1016/j.bmcl.2012.08.081.