Functionalization of 1,2,3-Triazole to Pyrimidine, Pyridine, Pyrazole, and Isoxazole Fluorophores with Antimicrobial Activity

Article abstract of DOI:10.1134/S1070363220030226

Abstract: The multi-component reaction of diacetyl triazole derivative with ethyl cyanoacetate and various aromatic aldehydes according to the conventional and solvent free methods leads to the corresponding 2-oxonicotinonitriles. A number of chalcones ha

Full text of DOI:10.1134/S1070363220030226

ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 3, pp. 476–482. © Pleiades Publishing, Ltd., 2020.
Functionalization of 1,2,3-Triazole to Pyrimidine, Pyridine,
Pyrazole, and Isoxazole Fluorophores with Antimicrobial Activity
A. M. Abdel Hamida, H. A. El-Sayeda, S. M. Mohammeda, A. H. Moustafaa, and H. A. Morsyb,*
a Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519 Egypt
b Higher Institution of Engineering and Modern Technology, Elmarg, Cairo, 33511 Egypt
*e-mail: heshselem@yahoo.com
Received January 9, 2020; revised January 19, 2020; accepted February 29, 2020
Abstract—The multi-component reaction of diacetyl triazole derivative with ethyl cyanoacetate and various aromatic
aldehydes according to the conventional and solvent free methods leads to the corresponding 2-oxonicotinonitriles.
Anumber of chalcones has been obtained via condensation of diacetyl triazole derivative with a variety of aromatic
aldehydes. Heterocyclization of dichalcones with thiourea, hydroxyl amine, 3-aminocrotononitrile and hydrazine
hydrate leads to a series of functionalized triazoles. Fluorescent properties of some products have been studied and
characterized by λem.max 463–499 nm. A series of newly synthesized compounds demonstrate high antimicrobial
activity against the tested microorganisms.
Keywords: triazole, pyridine, isoxazole, flourescence properties, solvent-free conditions
DOI: 10.1134/S1070363220030226
Biological activities of triazole derivatives have been
studied on a broad scale and are well documented in the
papers [1–3] and elsewhere. Antimicrobial properties of
triazole derivatives attracted our close attention as an
objective of the current research. Herein, we present the
development of our earlier optimized synthetic approach
to nitrogen containing heterocycle fluorophores [4–8] and
studies of their antimicrobial activity.
(4-chlorobenzaldehyde, 4-fluorobenzaldehyde, 4-ni-
trobenzaldehyde, 4-methoxybenzaldehyde, 3,4-dime-
thoxybenzaldehyde) in presence of ammonium acetate
afforded the corresponding pyridones 4a–4e. The process
was carried out by three different methods: conventional
(a), solvent free (b) and via intermolecular cyclization of
chalcones 5a–5e with ethyl cyanoacetate. The optimum
results (high yield and short reaction time) were achieved
under solvent-free conditions (Scheme 2). The structures
of 2-oxonicotinonitrile linked triazoles 4a–4e were con-
firmed by 1H NMR spectra that demonstrated new singlets
at 12.50–12.88 ppm (pyridone-NH) and IR spectra that
contained the bands in the regions of 3431–3448 (N–H),
2211–2218 (C≡N), and 1650–1657 cm–1 (C=O).
RESULTS AND DISCUSSION
Diazotization of p-aminoacetophenone (1) followed
by treatment with sodium azide furnished 1-(4-azidophe-
nyl)ethanone (2). Its following catalytic [3+2] cycload-
dition to acetyl acetone in presence of K2CO3 afforded
the diacetyl triazole derivative 3 (Scheme 1), structure of
which was supported by the spectral data.
Chalcone 5a underwent double pyrimidine cycliza-
tion upon refluxing with thiourea in ethanolic sodium
hydroxide solution leading to pyrimidinethione derivative
6 (yield 69%) (Scheme 3).
The multi-component reaction of triazole (3) with
ethyl cyanoacetate and a variety of aromatic aldehydes
Scheme 1. Synthetic route 1,2,3-triazole 3.
476

FUNCTIONALIZATION OF 1,2,3-TRIAZOLE
477
Scheme 2. Synthetic routes for nicotinonitriles 4a–4e and chalcones 5a–5e.
1H NMR spectrum of the product 6 demonstrated two
singlets at 6.5 and 11.20 ppm attributed to pyrimidine-H
and -NH, respectively. In 13C NMR spectrum the C=S
signal was recorded at 180.4 ppm. Its IR spectrum re-
vealed absorption bands at 3390 (N–H) and 1332 cm–1
(C=S). Cyclocondensation of 5a with hydroxylamine
gave isoxazole derivative 7, which was supported by 1H
NMR spectrum that demonstrated a singlet at 7.45 ppm
(isoxazole-H). Intermolecular cyclization of triazole
dichalcone 5b with 3-aminocrotononitrile 8 led to
nicotinonitrile derivative 9.
Finally, hydrazinolysis of dichalcone 5e afforded pyr-
azole derivative 10 whose 1H NMR spectrum revealed a
broad singlet at 13.38 ppm for the pyrazole-NH.
Fig. 2. Fluorescence spectra of 4a–4e.
Fig. 1. Absorption spectra of 4a–4e.
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ABDEL HAMID et al.
Scheme 3. Functionalization of chalcone 5a, 5b, 5e to pyrimidine, pyridine, isoxazole and pyrazole derivatives.
Fluorescent properties. Fluorescent properties of
for their in vitro antibacterial activity against Gram (+ve)
bacteria: Staphylococcus aureus ATCC 6538 and Mi-
crococci luteus ATCC 10240, and Gram (–ve) bacteria:
Pseudomonas aeruginosa ATCC 9027 and Escherichia
coli ATCC 10536. Antifungal activity was assessed
against Candida albicans ATCC 10231 and Aspergillus
niger ATCC 16404 using the agar-diffusion method.
Cefotaxime was used as an antibacterial standard, and
Nystatin was used as an antifungal standard.
triazole derivatives 4a–4e were measured in 1,4-diox-
ane and exhibited λabs.max 420–430 nm and maximum
fluorescence wavelengths λflu.max 471–503 nm (Table 1).
The λabs.max (Fig. 1) and λflu.max (Fig. 2) of 4c indicated
more significant bathochromic shifts than the other ana-
logues. Such effect could be attributed to higher conjuga-
tion in the π-system caused by the attached auxochromic
NO2 group.
The accumulated data (Table 2) indicated that all tested
compounds exhibited moderate to high antibacterial activ-
Antimicrobial activity. The newly synthesized tri-
azole derivatives 4a, 4b, 4e, 6, 7, 9, and 10 were tested
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FUNCTIONALIZATION OF 1,2,3-TRIAZOLE
479
Table 1. Absorption and fluorescence wavelengths of triazole
derivatives 4a–4e (c = 2.5×10–3 M)
ity (compared to cefotaxime) and high antifungal activity
(compared to nystatin) against the tested microorganisms.
Comp. no.
λ
abs. max, nm
425
λem. max, nm
471
EXPERIMENTAL
4a
4b
4c
4d
4e
All melting points are uncorrected and were mea-
sured on an Electro thermal IA 9100 apparatus. IR
spectra (KBr discs) were recorded on a PyeUnicam Sp-
3–300 or a Shimadzu FTIR 8101 PC spectrophotometer
(Cairo University, Cairo, Egypt). 1H and 13C NMR spec-
tra were measured on a BRUKER 400 MHz spectrom-
eter at Faculty of Science, Zagazig University, Egypt.
DMSO-d6 was used as a solvent. Fluorescence spectra
were measured on a JASCO-FP300 spectrophotometer
equipped with a 150-W xenon lamp source and quartz
cell of 1.0 cm path length. The slit width was 5 nm for
both excitation and emission (Zagazig University, Fac-
ulty of Science, Egypt). Elemental analysis was car-
ried out on a Perkin Elmer 240 (Cairo University, Cai-
ro, Egypt). Antimicrobial activity of the products was
tested at Microbiology Department, Faculty of Science,
Zagazig University.
421
430
420
426
472
503
475
485
down, filtered off, poured onto crushed ice and neutral-
ized with HCl. The precipitate formed was filtered off
and crystallized from H2O to give pure product 3 as a
white powder. Yield 40%, mp 110–112°C. IR spectrum,
ν, cm–1: 1685 (C=O, acetyl), 1601 (N=N). H NMR
1
spectrum, δ, ppm: 2.56 s (3H, COCH3-triazole), 2.65 s
(3H, CH3-triazole), 2.67 s (3H, p-COCH3), 7.80 d (2H,
J = 8.4 Hz, Ar-H), 8.18 d (2H, J = 8.8 Hz, Ar-H). Found,
%: C 64.24; H 5.34; N 17.32. C13H13N3O2. Calculated,
%: C 64.19; H 5.39; N 17.27.
Synthesis of 4a–4e. a. A mixture of an aromatic
aldehyde (p-chlorobenzaldehyde, p-fluorobenzaldehyde
and p-nitrobenzaldehyde, p-methoxybenzaldehyde, or
3,4-dimethoxybenzaldehyde) (10 mmol) with acetyl
triazole 3 (10 mmol), ethyl cyanoacetate (10 mmol) and
ammonium acetate (80 mmol) in absolute ethanol (20 mL)
was refluxed for 10 h. The formed product was filtered
off and crystallized from ethanol/AcOH to give the cor-
responding pure products as yellow powders.
1-(4-Azidophenyl)ethanone (2) [9]. A solution of
p-aminoacetophenone 1 (10 mmol) in dil. HCl was mixed
with solution of sodium nitrite (11 mmol) upon stirring.
The process was accompanied by liberation of brown gas-
es. Upon completion of the reaction, solution of sodium
azide (20 mmol) was added to the stirred mixture. The
product formed was filtered off and washed with water
to give pure product 2 as yellow powder. Yield 91%, mp
40–42°C. IR spectrum, ν, cm–1: 2100 (N3), 1672 (C=O).
b. Solvent-free process was carried out by fusing an
aromatic aldehyde with acetyl triazole 3 and ethyl cya-
noacetate in presence of ammonium acetate for 10 min.
The reaction mixture was triturated with ethanol and
crystallized from the solvent as above.
1-[4-(4-Acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-
phenyl]ethanone (3). A mixture of 1-(4-azidophenyl)-
ethanone (2) (10 mmol) with acetylacetone (10 mmol)
was heated at 70°C for 3 h in presence of potassium
carbonate (15 mmol). The reaction mixture was cooled
c. A mixture of a chalcone 5a–5e (10 mmol) with
ethyl cyanoacetate (10 mmol) and ammonium acetate
Table 2. Antimicrobial activity of some new synthesized triazole derivatives
Diameter of inhibition zones, mm
gram (–ve) bacteria
P. aeruginosa E. coli
22 21
Tested
compounds
gram (+ve) bacteria
S. aureus M. luteus
20 25
fungi
Candida albicans Aspergillus niger
4a
4b
4e
6
7
9
10
30
31
30
28
35
27
36
–
34
30
32
31
36
26
37
–
38
36
20
29
29
30
31
–
39
39
24
32
30
25
28
–
20
22
20
27
25
20
32
–
24
22
25
31
27
20
34
–
Cefotaxime
Nystatin
25
20
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ABDEL HAMID et al.
1
(80 mmol) in absolute ethanol (20 mL) was refluxed for
10 h. The formed product was filtered off and crystallized
from the solvent as above.
(C≡N), 1650 (C=O, amide), 1604 (N=N, triazole). H
NMR spectrum, δ, ppm: 1.90 s (3H, CH3-triazole), 3.85 s
(6H, 2OCH3), 6.97 s (2H, Ar-H), 7.12 d (4H, J = 8.0 Hz,
Ar-H), 7.69 d (2H, J = 8.4 Hz, Ar-H), 7.76 d (2H, J =
8.0 Hz, Ar-H), 7.81 d (2H, J = 8.4 Hz, Ar-H), 8.17 d (2H,
J = 8.0 Hz, Ar-H), 12.50 br (2H, 2NH). 13C NMR spec-
trum, δ, ppm: 21.05, 55.44, 55.47, 114.2, 114.3, 116.5,
116.7, 125.3, 125.5, 125.6, 127.8, 127.9, 129.2, 129.3,
129.7, 129.9, 130.1, 135.1, 136.7, 137.0, 137.9, 142.9,
159.0, 161.0, 161.2, 162.3, 172.0, 193.3. Found, %: C
69.23; H 4.11; N 16.10. C35H25N7O4. Calculated, %: C
69.18; H 4.15; N 16.14; O, 10.53.
4-(4-Chlorophenyl)-6-(4-{4-[4-(4-chlorophenyl)-5-
cyano-6-oxo-1,6-di-hydropyridin-2-yl]-5-methyl-1H-
1,2,3-triazol-1-yl}phenyl)-2-oxo-1,2-dihydropyridine-
3-carbonitrile (4a). Yield, %: 53 (a), 73 (b); mp 300–
302°C. IR spectrum, ν, cm–1: 3431 (NH), 2218 (C≡N),
1
1652 (C=O, amide), 1509 (N=N, triazole). H NMR
spectrum, δ, ppm: 2.66 s (3H, CH3-triazole), 7.65–7.68 m
(4H, Ar-H), 7.74 d (2H, J = 8.4 Hz, Ar-H), 7.79–7.85 m
(6H, Ar-H), 8.17–8.23 m (2H, Ar-H), 12.88 br
(2H, 2NH). 13C NMR spectrum, δ, ppm: 10.1, 115.8,
126.4, 128.5, 104.8, 110.8, 115.3, 115.8, 122.5, 128.7,
130.0, 130.8, 133.5, 133.7, 135.1, 137.8, 139.3, 157.4,
159.4, 160.0. Found, %: C 64.33; H 3.16; N 15.85.
C33H19Cl2N7O2. Calculated, %: C 64.30; H 3.11; N 15.90.
6-(4-{4-[5-Cyano-4-(3,4-dimethoxyphenyl)-
6-oxo-1,6-dihydropyridin-2-yl]-5-methyl-1H-1,2,3-tri-
azol-1-yl}phenyl)-4-(3,4-dimethoxyphenyl)-2-oxo-1,2-
dihydropyridine-3-carbonitrile (4e). Yield, %: 48 (a),
60 (b); mp 320–322°C, IR spectrum, ν,cm–1: 3439 (NH),
2216 (C≡N), 1657 (C=O, amide), 1607 (N=N, triazole).
1H NMR spectrum, δ, ppm: 1.90 s (3H, CH3-triazole),
3.85 s (12H, 4OCH3), 7.02 s (1H,Ar-H), 7.16 m (2H,Ar-
H), 7.33–7.38 m (3H, Ar-H), 7.83 m (2H, Ar-H), 8.17 m
(2H, Ar-H), 8.17 m (2H, Ar-H), 12.51 br (2H, 2 NH).
13C NMR spectrum, δ, ppm: 10.1, 56.1, 104.8, 110.8,
111.7, 112.8, 115.3, 115.8, 122.4, 122.5, 125.8, 126.4,
130.8, 133.5, 135.1, 137.8, 139.3, 149.7, 157.4, 159.4,
160.2. Found, %: C 66.52; H 4.41; N 14.63. C37H29N7O6.
Calculated, %: C 66.56; H 4.38; N 14.68.
6-(4-{4-[5-Cyano-4-(4-fluorophenyl)-6-oxo-1,6-
dihydropyridin-2-yl]-5-methyl-1H-1,2,3-triazol-1-yl}-
phenyl)-4-(4-fluorophenyl)-2-oxo-1,2-dihydropyri-
dine-3-carbonitrile (4b). Yield, %: 34 (a), 50 (b); mp
326°C (decomp.). IR spectrum, ν, cm–1: 3448 (NH), 2212
(C≡N), 1653 (C=O, amide), 1602 cm–1 (N=N, triazole).
1H NMR spectrum, δ, ppm: 1.90 s (3H, CH3-triazole),
7.42 d (2H, J = 8.4 Hz, Ar-H), 7.47 d (2H, J = 8.8 Hz,
Ar-H), 7.79–7.87 m (7H,Ar-H), 8.19–8.22 m (3H,Ar-H),
12.85 br (2H, 2NH). Found: C 67.96; H 3.25; N 16.83.
C33H19F2N7O2. Calculated, %: C 67.92; H 3.28; N 16.80.
Synthesis of chalcones 5a–5e. A mixture of
compound 3 (10 mmol) with an aromatic aldehyde
(20mmol)wasstirredinpresenceofNaOH(20%)inethanol
(20 mL) for 1–3 h. The precipitate formed was filtered
off, washed with water, dried, and recrystallized from
EtOH–AcOH as yellow powder.
6-(4-{4-[5-Cyano-4-(4-nitrophenyl)-6-oxo-1,6-
dihydropyridin-2-yl]-5-methyl-1H-1,2,3-triazol-1-yl}-
phenyl)-4-(4-nitrophenyl)-2-oxo-1,2-dihydropyridine-
3-carbonitrile (4c). Yield, %: 17 (a), 33 (b); mp 240°C
(decomp.), IR spectrum, ν, cm–1: 3432 (NH), 2211 (C≡N),
1
1651 (C=O, amide), 1604 (N=N, triazole). H NMR
3-(4-Chlorophenyl)-1-(4-{4-[3-(4-chlorophenyl)-
acryloyl]-5-methyl-1H-1,2,3-triazol-1-yl}phenyl)-
prop-2-en-1-one (5a). Yield 83%, mp 266–268°C. IR
spectrum, ν, cm–1: 1666 (C=O), 1603 (N=N, triazole).
1H NMR spectrum, δ, ppm: 1.90 s (3H, CH3-triazole),
7.31–8.43 m (16H, Ar-H + olefinic-H). 13C NMR spec-
trum, δ, ppm: 9.5, 121.3, 123.1, 128.7, 129.0, 129.9,
133.3, 133.5, 137.9, 139.3, 141.7, 145.1, 187.0, 189.7.
Found, %: C 66.43; H 3.96; N 8.54. C27H19Cl2N3O2.
Calculated, %: C 66.40; H 3.92; N 8.60.
spectrum, δ, ppm: 1.90 s (3H, CH3-triazole), 7.85 d (2H,
J = 8.4 Hz, Ar-H), 7.99 d (2H, J = 8.4 Hz, Ar-H), 8.03 d
(2H, J = 8.8 Hz, Ar-H), 8.05 s (1H, Ar-H), 8.21–8.23 m
(5H, Ar-H), 8.41 d (2H, J = 8.8 Hz, Ar-H), 12.51 br (2H,
2NH). 13C NMR spectrum, δ, ppm: 10.1, 104.8, 110.8,
115.3, 115.8, 122.5, 123.8, 126.4, 130.1, 130.8, 133.5,
135.1, 137.8, 139.3, 141.7, 147.1, 157.4, 159.4, 160.2.
Found, %: C 62.14; H 3.07; N 19.74. C33H19N9O6. Cal-
culated, %: C 62.17; H 3.00; N 19.77.
6-(4-{4-[5-Cyano-4-(4-methoxyphenyl)-6-oxo-1,6-
dihydropyridin-2-yl]-5-methyl-1H-1,2,3-triazol-1-yl}-
phenyl)-4-(4-methoxyphenyl)-2-oxo-1,2-dihydropyr-
idine-3-carbonitrile (4d). Yield, %: 58 (a), 75 (b); mp
260°C (decomp.). IR spectrum, ν,cm–1: 3435 (NH), 2217
3-(4-Fluorophenyl)-1-(4-{4-[3-(4-fluorophenyl)-
acryloyl]-5-methyl-1H-1,2,3-triazol-1-yl}phenyl)-
prop-2-en-1-one (5b). Yield 84%, mp 230–232°C. IR
spectrum, ν, cm–1: 1666 (C=O), 1597 (N=N, triazole).
1H NMR spectrum, δ, ppm: 1.90 s (3H, CH3-triazole),
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FUNCTIONALIZATION OF 1,2,3-TRIAZOLE
481
1
7.08–8.04 m (14H, Ar-H + olefinic-H), 8.40 d (2H,
J = 8.4 Hz, Ar-H). Found, %: C 71.25; H 4.16; N 9.19.
C27H19F2N3O2. Calculated, %: C 71.20; H 4.20; N 9.23.
1332 (C=S). H NMR spectrum, δ, ppm: 2.64 s (3H,
CH3-triazole), 6.50 s (2H, H-pyrimidine), 7.28 d (2H, J =
7.9 Hz, Ar-H), 7.56 d (4H, J = 8.4 Hz, Ar-H), 7.58 d (2H,
J = 7.8 Hz,Ar-H), 7.79 d (4H, J = 8.4 Hz,Ar-H), 11.20 br
(2H, 2NH). 13C NMR spectrum, δ, ppm: 10.25, 103.9,
109.9, 122.5, 122.8, 126.4, 130.6, 130.8, 131.2, 133.5,
133.9, 134.4, 134.8, 135.1, 135.6, 135.9, 136.3, 136.6,
139.3, 157.8, 164.6, 179.9, 180.4. Found, %: C 57.94; H
3.23; N 16.30. C29H19Cl2N7S2. Calculated, %: C 58.00;
H 3.19; N 16.33.
1-{5-Methyl-1-[4-(3-[4-nitrophenyl]acryloyl)-
phenyl]-1H-1,2,3-triazol-4-yl}-3-(4-nitrophenyl)prop-
2-en-1-one (5c). Yield 68%, mp 142–144°C. IR spectrum,
1
ν, cm–1: 1677 (C=O), 1600 (N=N, triazole). H NMR
spectrum, δ, ppm: 2.67 s (3H, CH3-triazole), 7.70–8.30 m
(16H, Ar-H + olefinic-H). 13C NMR spectrum, δ, ppm:
9.5, 121.3, 123.1, 123.8, 129.0, 129.9, 133.5, 137.9,
139.3, 141.3, 141.7, 145.1, 147.1, 187.0, 189.7. Found,
%: C 63.61; H 3.80; N 13.72. C27H19N5O6. Calculated,
%: 63.65; H 3.76; N 13.75.
5-(4-Chlorophenyl)-3-(4-{4-[5-(4-chlorophenyl)-
isoxazol-3-yl]-5-methyl-1H-1,2,3-triazol-1-yl}phenyl)-
isoxazole (7). A mixture of chalcone 5a (2 mmol) with
hydroxyl amine hydrochloride (4 mmol) was refluxed in
presence of NaOH (4 mmol) in ethanol (15 mL) medium
for 12 h. Progress of the reaction was monitored by TLC.
Upon completion of the process, the reaction mixture was
cooled down, poured onto crushed ice and neutralized
with conc. HCl. The precipitate formed was filtered off
and crystallized from ethanol–AcOH as a pale brown
powder. Yield 44%, mp 182–184°C. IR spectrum, ν,
cm–1: 1600 (N=N, triazole), 1091 (O–C of isoxazole). 1H
NMR spectrum, δ, ppm: 2.64 s (3H, CH3-triazole), 7.45 s
(2H, H-isoxazole), 7.62 d (4H, J = 8.4 Hz, Ar-H), 7.69 d
(2H, J = 7.8 Hz, Ar-H), 7.75–8.06 m (6H, Ar-H). 13C
NMR spectrum, δ, ppm: 9.6, 98.3, 124.7, 124.9, 127.5,
128.2, 129.3, 130.1, 133.5, 134.3, 135.9, 143.9, 150.0,
162.0, 169.3. Found, %: C 63.01; H 3.30; N 13.67.
C27H17Cl2N5O2. Calculated, %: C 63.05; H 3.33; N 13.62.
3-(4-Methoxyphenyl)-1-(4-{4-[3-(4-methoxyphe-
nyl)acryloyl]-5-methyl-1H-1,2,3-triazol-1-yl}phenyl)-
prop-2-en-1-one (5d). Yield 95%, mp 156–158°C. IR
spectrum, ν,cm–1: 1665 (C=O), 1594 (N=N, triazole). 1H
NMR spectrum, δ, ppm: 2.67 s (3H, CH3-triazole), 3.83 s
(6H, 2OCH3), 7.03 d (2H, J = 7.6 Hz,Ar-H), 7.76–7.93 m
(12H, Ar-H + olefinic-H), 8.38 d (2H, J = 8.8 Hz, Ar-H).
Found, %: C 72.61; H 5.29; N 8.72. C29H25N3O4. Calcu-
lated, %: C 72.64; H 5.25; N 8.76.
3-(3,4-Dimethoxyphenyl)-1-(4-{4-[3-(3,4-dimeth-
oxyphenyl)acryloyl]-5-methyl-1H-1,2,3-triazol-
1-yl}phenyl)prop-2-en-1-one (5e). Yield 89%, mp
140–142°C. IR spectrum, ν, cm–1: 1660 (C=O), 1587
(N=N, triazole). 1H NMR spectrum, δ, ppm: 2.64 s (3H,
CH3-triazole), 3.87 s (6H, 2OCH3), 3.88 s (6H, 2OCH3),
7.03 d (2H, J = 8.4 Hz, Ar-H), 7.38–7.45 m (3H, Ar-H),
7.58 s (1H, Ar-H), 7.76–7.94 m (6H, Ar-H + olefinic-
H), 8.39 d (2H, J = 8.4 Hz, Ar-H). 13C NMR spectrum,
δ, ppm: 10.02, 54.88, 55.61, 55.74, 110.7, 110.8, 111.5,
111.7, 119.3, 120.4, 123.5, 124.3, 125.5, 127.1, 127.3,
129.8, 138.2, 138.7, 138.9, 143.3, 143.7, 145.4, 149.0,
149.4, 151.4, 151.5. Found, %: C 69.05; H 5.46; N 7.75.
C31H29N3O6. Calculated, %: C 69.00; H 5.42; N 7.79.
6-(4-{4-[5-Cyano-4-(4-fluorophenyl)-6-methylpyri-
din-2-yl]-5-methyl-1H-1,2,3-triazol-1-yl}phenyl)-4-(4-
fluorophenyl)-2-methylnicotinonitrile (9). A mixture
of chalcone 5b (2 mmol) with 3-aminocrotononitrile (8)
(4 mmol) was refluxed in presence of NaOH (4 mmol) in
ethanol (15 mL) medium for 12 h. Progress of the reaction
was monitored by TLC. Upon completion of the process,
the reaction mixture was cooled down and poured onto
crushed ice. The precipitate was filtered off and crystal-
lized from ethanol/AcOH as a pale yellow powder. Yield
43%, mp 102–104°C. IR spectrum, ν, cm–1: 2218 (C≡N),
1596 (N=N, triazole). 1H NMR spectrum, δ, ppm: 2.64 s
(3H, CH3-triazole), 2.79 s (6H, 2 CH3-pyridine), 7.31 d
(2H, J = 8.6 Hz, Ar-H), 7.34 s (1H, H-pyridine), 7.69 d
(2H, J = 7.8 Hz, Ar-H), 7.76–7.86 m (6H, Ar-H), 8.22 s
(1H, H-pyridine), 8.49 d (2H, J = 7.8 Hz,Ar-H). 13C NMR
spectrum, δ, ppm: 9.61, 26.7, 110.2, 115.9, 116.0, 127.6,
130.1, 130.7, 133.5, 134.5, 134.6, 139.0, 143.9, 154.5,
4-(4-Chlorophenyl)-6-(4-{4-[6-(4-chlorophenyl)-2-
thioxo-2,3-dihydropyrimidin-4-yl]-5-methyl-1H-1,2,3-
triazol-1-yl}phenyl)pyrimidine-2(1H)-thione (6). A
mixture of chalcone 5a (2 mmol) with thiourea (4 mmol)
was refluxed in presence of NaOH (4 mmol) and ethanol
(15 mL) for 12 h. Progress of the reaction was monitored
by TLC. Upon completion of the process, the reaction
mixture was cooled down, poured onto crushed ice and
neutralized with conc. HCl. The precipitate formed was
filtered off and crystallized from ethanol–AcOH as a pale
brown powder. Yield 69%, mp 216–218°C. IR spectrum,
ν, ppm: 3390 (NH), 1620 (C=N), 1593 (N=N, triazole),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 3 2020

482
ABDEL HAMID et al.
2. Swamy, M.K., Swapna, M., Sandeep, T., and Ven-
kateswar Rao, P., Russ. J. Gen. Chem., 2019, vol. 89,
p. 1884.
158.8, 159.5, 160.9. Found, %: C 72.49; H 4.06; N 16.97.
C35H23F2N7. Calculated, %: C 72.53; H 4.00; N 16.92.
4-[5-(3,4-Dimethoxyphenyl)-1H-pyrazol-3-yl]-
1-{4-[5-(3,4-dimethoxy-phenyl)-1H-pyrazol-3-yl]-
phenyl}-5-methyl-1H-1,2,3-triazole (10). A mixture of
chalcone 5e (2 mmol) with hydrazine hydrate (4 mmol)
was refluxed in medium of ethanol (15 mL) for 12 h.
Progress of the reaction was confirmed by TLC. Upon
completion of the process, the reaction mixture was
cooled down and poured onto crushed ice. The precipitate
was filtered off and crystallized from ethanol–AcOH as a
yellow powder. Yield 66%, mp 236–238°C. IR spectrum,
https://doi.org/10.1134/S107036321909024X
3. Nelkanzi, N.A.A., El-Sofany, W.I., Gab-Allah, S.M.,
Mohamed, A.M., Kutkate, O., and El-Sayed, W.A.
Russ. J. Gen. Chem., 2019, vol. 89, p. 1896.
https://doi.org/10.1134/S1070363219090263
4. El-Sayed, H.A.,Abdel Hamid,A.M.,Assy, M.G., and Far-
ag, T.S., Synth. Commun., 2018, vol. 48, p. 794.
https://doi.org/10.1080/00397911.2017.1422522
5. El-Sayed, H.A., Abdel Hamid, A.M., Mohammed, S.M.,
and Moustafa, A.H., Synth. Commun. 2019, vol. 49,
p. 2096.
1
ν, cm–1: 3433 (NH), 1597 (N=N, triazole). H NMR
spectrum, δ, ppm: 2.65 s (3H, CH3-triazole), 3.85 s (6H,
2OCH3), 3.88 s (6H, 2OCH3), 6.90–8.19 m (12H,Ar-H),
13.38 br (2H, 2NH). 13C NMR spectrum, δ, ppm: 9.6,
56.1, 99.7, 100.7, 108.4, 111.0, 120.8, 127.5, 128.3, 130.1,
133.0, 133.5, 135.9, 143.9, 146.6, 146.7, 147.7, 149.8,
150.3. Found, %: C 66.03; H 5.24; N 17.47. C31H29N7O4.
Calculated, %: C 66.06; H 5.19; N 17.40.
https://doi.org/10.1080/00397911.2019.1616760
6. El-Sayed, H.A., and Morsy, H.A., J. Iran. Chem. Soc.,
2019, vol. 16, p. 723.
https://doi.org/10.1007/s13738-018-1548-z
7. El-Sayed, H.A., and Said, S.A., J. Heterocyclic Chem.,
2019, vol. 56, p. 1030.
https://doi.org/10.1002/jhet.3488
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 3 2020