SYNTHESIS, IDENTIFICATION OF SOME
NEW TETRAZOLINE, THIAZOLIDIN-4-ONE
AND IMIDAZOLIDIN-4-ONE DERIVATIVES
AND EVALUATION ANTICANCER OF THEIR
MOLECULAR DOCKING AND ANTI-
OXIDANT EXPERIMENTAL
Mohammed B. wathiq AL-tamimi
Department of Chemistry, College of Science, University of Baghdad,
Baghdad, Iraq
mohammed.baqer1205m@sc.uobaghdad.edu.iq
Suaad M. H. Al-Majidi
Department of Chemistry, College of Science, University of Baghdad,
Baghdad, Iraq
Reception: 25/10/2022 Acceptance: 26/12/2022 Publication: 21/02/2023
Suggested citation:
Mohammed B. wathiq AL-tamimi and Suaad M. H. Al-Majidi. (2023).
Synthesis, identification of some new tetrazoline, thiazolidin-4-one and
imidazolidin-4-one derivatives and evaluation anticancer of their
molecular docking and anti-oxidant experimental. 3C TIC. Cuadernos de
desarrollo aplicados a las TIC, 12(1), 83-116. https://doi.org/
10.17993/3ctic.2023.121.83-116
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
83
ABSTRACT
In this study, a new series of 1,3-dimethyl-6-(amino aceto hydrazine) pyrimidine-2,4-
dione-6-yl with 4-substituted benzyldehyde, The compound (1-5) was synthesized in a
single pot that cyclization by the addition of sodium azide, 2-mercapto acid & 2-amino
acetic acid to produce five-membered heterocyclic rings includes: tetrazoline-1yl
(6-10), thiazolidin-4-one (11-15) and imidazolidin-4-one (16-20) derivatives
respectively. These compounds were characterized using spectral methods [FTIR and
1HNMR, 13C-NMR for some of them] evaluations, measurements, and analyses of
their physical qualities. Each molecule was evaluated for antioxidant activity in vitro to
use the DPPH and phosphomolybdenum methods. When compared to the standard
drug Ascorbic acid, (1-20) demonstrated promising antioxidant activity among the
bioactive molecules synthesized. Furthermore, molecular docking against, substances
showed superiority over the standard medication Exemestane in tests of the
Aromatase enzyme.
KEYWORDS
Tetrazoline, Thiazolidin-4-one, Imidazolidin-4-one, molecular docking and Anti-oxidant
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
84
PAPER INDEX
ABSTRACT
KEYWORDS
1. INTRODUCTION
2. MATERIALS AND METHODS
2.1. SYNTHESIS OF 1,3-DIMETHYL-6- (AMINO ACETO HYDRAZIDE
BENZYLIDENE)- PYRAMIDINE-2, 4-DIONE-6-YL.(1-5)[24, 25]
2.2. SYNTHESIS OF 1,3-DIMETHYL-6-AMINO ACETAMIDE[5-(4-
SUBSTITUTED PHENYL)-2H-TETRAZOLINE-1-YL]-PYRAMIDINE-2,4-
DIONE-6-YL.(6-10) [26, 27]
2.3. SYNTHESIS OF 1,3-DIMETHYL-6-AMINO ACETAMIDE[2-(4-
SUBSTITUTED PHENYL)-THIAZOLIDIN-4-ONE-3-YL]- PYRAMIDINE-2,4-
DIONE-6-YL.(11-15)[28]
2.4. SYNTHESIS OF 1,3-DIMETHYL-6-AMINO ACETAMIDE[2-(4-
SUBSTITUTED PHENYL)-IMIDAZOLIDINE-4-ONE-3-YL]-PYRAMIDINE-2,4-
DIONE-6-YL.(16-20)[29, 30]
2.5. ACTIVATION OF ANTIOXIDANT DEFENSES (DPPH RADICAL
SCAVENGING ASSAY)[31, 32]
2.6. TOTAL ANTIOXIDANT CAPACITY[33]
2.7. IN SILICO STUDIES
2.7.1. PREPARATION OF THE LIGAND[2]
2.7.2. DETERMINING PROTEIN BINDING REGIONS
2.7.3. MOLECULAR DOCKING INVESTIGATION
3. RESULTS AND DISCUSSION
3.1. SCHEME-1 SYNTHESIS OF NEW TETRAZOLINE, THIAZOLIDIN-4-ONE,
AND IMIDAZOLIDINE-4-ONE DERIVATIVES
3.2. DPPH SCAVENGING ACTIVITY
3.3. QUANTITATIVE MEASURE OF ANTIOXIDANT CAPACITY
3.4. DOCKING STUDIES
4. CONCLUSION
REFERENCES
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
85
1. INTRODUCTION
Uracil is an essential pyrimidine representative. It is one of the five nucleobases
and a promising structure in many natural products [1]. Uracil derivatives are
important intermediates in the purine synthesis. One of the four nucleobases that
make up RNA, it is a pyrimidine derivative that occurs naturally. In RNA, uracil couples
to adenine via two hydrogen bonds. DNA with thymine instead of uracil [2, 3].
Compounds containing a high nitrogen content constitute a distinct class of C-N
heteroaromatic compounds [4]. The tetrazoline ring structure contains unsaturated
bonds, which ensures good energy properties [5]. Due to its high nitrogen
concentration, enthalpy of formation [6], and inclination toward lesser sensitivity,
tetrazoline is commonly employed in the construction of high-energy density materials
[7].
Thiazolidinone derivatives have a five-membered heterocyclic ring with one sulfur,
one nitrogen, and three carbon atoms Thiazolidinones are one of the most essential
heterocyclic compounds [8], and their derivatives, which have a carbonyl group in the
fourth position, are an integral part of many synthetic pharmaceuticals with diverse
biological activities [9, 10]
4-Imidazolidinones are a class of nitrogen-rich saturated lactams with medicinal
applications [11]. Imidazolidinone derivatives are currently of interest as
organocatalysts in modern organic synthesis [12]. 4-Imidazolidinones are cyclic
amides, whereas 2-Imidazolidinones are cyclic urea compounds. illustrates
imidazolidinone isomers [13]. The imidazolidin-2-one motif is frequently found in
natural products1,2 as well as pharmaceutically interesting synthetic molecules [14].
as a result of their ease of synthesis, uracil derivatives are regarded as promising
compounds in drug discovery. The pyrimidine core is an important pharmacophore
moiety of biologically active natural and synthetic compounds that compete for the
same binding sites[15] the most conmen biological activities of uracil derivatives in the
last years application Antioxidan t[2], Anti-flamatory [16], Anticaner [17], Anti-leukemia
[18], Antibacterial [19, 20], anti-tumour [21], anti-angiogenesis [22] and Anti-diabetic
[23].
2. MATERIALS AND METHODS
The investigation relied on unpurified chemicals purchased from BDH, Fluka,
Merck, and Sigma Aldrich. In addition, an Electro thermal melting point device was
used to record the melting points, although no corrections were made. Using a
SHIMAZU FTIR-8400 Fourier transform Infrared spectrophotometer, KBr discs were
used to record the (4000-600) cm-1 FTIR spectra of the produced compounds. Using
a BRUKER 400MHz equipment, TMS was used as the internal standard, and DMSO-
d6 was used as the solvent in order to get 1H- and 13C-NMR spectra in Iraq. The
Adiwaniyah Technical Institute and the Al-Forat Alawsat University both employed
Japanese Shimadzu 1900i spectrophotometers.
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
86
2.1. SYNTHESIS OF 1,3-DIMETHYL-6- (AMINO ACETO
HYDRAZIDE BENZYLIDENE)- PYRAMIDINE-2, 4-DIONE-6-
YL.(1-5)[24, 25]
A solution of (0.5 g, 0.022 mol.) 1,3-dimethyl-6-(amino aceto hydrazine)
pyrimidine-2,4-dione-6-yl, (0.022 mol.) para substituted aromatic aldehydes in (10 mL)
of ethanol absolute as a solvent were thoroughly mixed with glacial acetic acid as a
catalytic three drops of, and the mixture was refluxed for (6-10) house. The product
was filtrated, water washed and recrystallized by ethanol Table-2 lists characteristics
of compounds in terms of their physical properties (6-10) as well as FTIR spectral
data.
2.2. SYNTHESIS OF 1,3-DIMETHYL-6-AMINO ACETAMIDE[5-(4-
SUBSTITUTED PHENYL)-2H-TETRAZOLINE-1-YL]-
PYRAMIDINE-2,4-DIONE-6-YL.(6-10) [26, 27]
Compounds (6-10) were obtained from reaction of an equimolar a combination of
Schiff bases (1-5) (0.0009 mol.) in ethanol (10 mL). Sodium azide (0.05 g, 0.0009
mol.) dissolved in the same solvent was added and the solution was reflex for (18-20)
house. The product was filtrated, water washed and recrystallized by ethanol Table-2
lists some of the physical properties of compounds (6-10) as well as FTIR spectral
data.
2.3. SYNTHESIS OF 1,3-DIMETHYL-6-AMINO ACETAMIDE[2-(4-
SUBSTITUTED PHENYL)-THIAZOLIDIN-4-ONE-3-YL]-
PYRAMIDINE-2,4-DIONE-6-YL.(11-15)[28]
Throughout this step, (0.0009 mol.) of compound (1-5) of Schiff bases and (0.06
mL., 0.0009 mol.) of 2-mercaptoacetic acid were added dropwise to THF (10 mL).
After that, the reaction mixture was heated to reflux temperature (20-24). The mixture
was filtered, washed, and purified further with ethanol to recrystallization. Table-3
contains a list of a variety of physical properties of compounds (11-15) as well as FTIR
spectral data.
2.4. SYNTHESIS OF 1,3-DIMETHYL-6-AMINO ACETAMIDE[2-(4-
SUBSTITUTED PHENYL)-IMIDAZOLIDINE-4-ONE-3-YL]-
PYRAMIDINE-2,4-DIONE-6-YL.(16-20)[29, 30]
An equimolar amount of Schiff bases (1-5) is added to a mixture (0.0009 mol.) As a
solvent, (10 mL) of ethanol was stirred in, with (0.25 g, 0.0009 mol.) 2-aminoacetic
acid in the same solvent and the mixture solution was refluxed for (20-22) house. The
resulting mix was then result of filtering being reformed from acetone crystals after
being allowed to cool to room temperature. Table-3 lists a variety of physical
properties of compounds (16-20) as well as FTIR spectral data.
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
87
Table 1. the physical properties as well as the FTIR spectral data cm-1 of the compounds that
were produced (1-5).
Com.
No.
Physical properties Major FTIR Absorptions cm-1
Compound Structure
m.p
°C
Yiel
d
%
Color νN-H
νC-H
Arom.
Aliph.
ν(C=O
)
ν(C=N
)
ν(C=C
)
Other
bands
1
88-90 80 Pale
gray 3282
3053
2952
1701
1681
1639
1623
-
2
222-2
23 85 yellow 3294
3001
2975
1701
1683
1639
1620
(NO2)
Asym.
1521
Sym. 1346
3
187-1
88 77 Light
gray 3294
3099
2997
2943
1731
1683
1649
1625
(C-Cl)
1091
4
268-2
70 70 Light
yellow 3301
3028
2960
1730
1656
1627
1619
ν(-OH)
3433
5
250-2
51 85 Reddish
yellow 3292
3060
2979
1699
1681
1639
1620
-
N
N
O
CH
3
O
CH
3
NH
H
N
N
O
C
H
N
CH
3
CH
3
N
N
O
CH
3
O
CH
3
NH
H
N
N
O
C
H
NO
2
N
N
O
CH3
O
CH3
NH
H
N
N
O
C
H
OH
N
N
O
CH
3
O
CH
3
NH
H
N
N
O
C
H
N
N
O
CH
3
O
CH
3
NH
H
N
N
O
C
H
Cl
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
88
Table 2. the physical properties as well as the FTIR spectral data cm-1 of the compounds that
were produced (6-10).
Com.
No.
Physical properties Major FTIR Absorptions cm-1
Compound Structure
m.p
°C
Yield
%
Color νN-H
νC-H
Arom
.
Aliph.
ν(C=O
)
ν(C=C
)
Other
bands
6359-3
60 80 Deep
yellow 3275
3023
2923
1708
1668
1620
ν(N=N)
1450
7310-3
11 77 Light
yellow 3290
3024
2975
1703
1687
1622
ν(N=N)
1451
ν(NO2)
Asym.
1523
Sym. 1346
8359-3
60 75 Yellow 3286
3077
2997
1711
1685 1625
ν(C-Cl)
1089
ν(N=N)
1453
9260-2
61 84 Deep
gray 3319
3028
2958
1710
1682
1608
ν(N=N)
1448
ν(-OH)
3406
10 268-2
69 83 Yellow 3282
3050
2962
1703
1685
1625
ν(N=N)
1457
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
HN
N
N
Cl
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
HN
N
N
NO
2
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
HN
N
N
N
CH
3
CH
3
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
HN
N
N
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
HN
N
N
OH
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
89
Table 3. the physical properties as well as the FTIR spectral data cm-1 of the compounds that were
produced (11-15).
Com.
No.
Physical properties Major FTIR Absorptions cm-1
Compound Structure
m.p
°C
Yield
%
Color νN-H
νC-H
Arom
.
Aliph.
ν(C=O
)
ν(C=C
)
Other
bands
11 270-2
71 81 Light
yellow 3350
3060
2956
1699
1674
1620
ν(C-S)
709
12 302-3
03 84 Yellow 3382
3002
2974
1701
1685
1618
ν(NO2)
Asym.
1521
Sym. 1346
ν(C-S)
702
13 212-2
13 78 Deep
gray 3286
3097
2983
1733
1683
1625
ν(C-Cl)
1091
ν(C-S)
700
14 230-2
31 79 Deep
gray
3269
3253
3060
2974
1701
1683
1626
ν(-OH)
3444
ν(C-S)
703
15 264-2
65 82 Yellow 3284
3060
2981
1701
1685
1628
ν(C-S)
696
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
S
N
O
CH
3
CH
3
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
S
O
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
S
OH
O
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
S
Cl
O
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
S
NO
2
O
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
90
Table 4. the physical properties as well as the FTIR spectral data cm-1 of the compounds that
were produced (16-20).
2.5. ACTIVATION OF ANTIOXIDANT DEFENSES (DPPH
RADICAL SCAVENGING ASSAY)[31, 32]
Activation of antioxidant defenses was measured for a range of compounds (1-20)
using a conventional method and the stable DPPH free radical. The compounds 1–20
were produced in DMSO at three different concentrations (50, 100, and 150) M, after
which it was put to a methanol solution (of up to 2 milliliters) that contained 0.0002
grams per milliliter of DPPH radical. After 30 minutes of room temperature incubation,
the spectrophotometer was utilized for determining the absorbance of the reaction
mixture at a wavelength of 517 nm. Ascorbic acid served as a reference substance
when evaluated at the same quantities as the other substances. To determine how
effective ascorbic acid was in blocking DPPH radicals, we used the following formula:
((Ac-As)/Ac) *100. (percentage). An absorbance measurement taken from a control
(Ac) and one taken from a sample (As) are shown.
Com.
No.
Physical properties Major FTIR Absorptions cm-1
Compound Structure
m.p
°C
Yield
%
Color νN-H
νC-H
Arom
.
Aliph.
ν(C=O
)
ν(C=C
)
Other
bands
16 253-
254 81 Yellow 3180
3051
2977
1731
1666
1612 -
17 270-
271 86 Deep
yellow 3211
3050
2958
1693
1672
1630
ν(NO2)
Asym.
1521
Sym. 1344
18 193-
194 79 Deep
gray 3180
3049
2995
1713
1662
1622
ν(C-Cl)
1089
19 224-
225 75 Reddish
yellow
3180 3062
2987
1692
1662
1610
ν(-OH)
3413
20 262-
263 82 Light
yellow 3298
3060
2977
1701
1683
1625 -
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
NH
O
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
NH
OH
O
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
NH
Cl
O
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
NH
NO
2
O
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
NH
N
O CH
3
CH
3
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
91
2.6. TOTAL ANTIOXIDANT CAPACITY[33]
It was revealed that the compounds that were synthesized had a total antioxidant
capability when they were tested with the phosphomolybdenum technique. An aliquot
of a solution containing the chemical was combined with one milliliter of reagent that
included 0.6 M sulphuric acid, 28 mM (Na2HPO4), and those were all included (4 mM
ammonium molybdate). After that, a hermetic seal was placed on each of the test
tubes that contained the reaction solution for the compounds that were being
analyzed, and the tubes were then heated to 95 degrees Celsius for an hour and a
half. After bringing the temperature in the room up to room temperature, a
spectrophotometer was used to measure the absorbance of each tube at 695 nm in
comparison to a blank. The total antioxidant activity is reported as the amount of
ascorbic acid that is comparable to one gram. For the purpose of plotting the
calibration curve, the following concentrations of ascorbic acid in DW were used: 10,
20, 30, 50, 70, 90, 120, 180, and 200 g/mL.
2.7. IN SILICO STUDIES
2.7.1. PREPARATION OF THE LIGAND[2]
Molecular docking research was carried out making use of the Small Drug
Research Suites software package (Schrodinger 2020-3, LLC). The two-dimensional it
was decided to draw out the structures of the freshly produced substances, and then
Maestro 12.5 was used to turn those drawings into three-dimensional structures.
Before docking, the ligands' pH levels were brought up to the physiological range
using the OPLS2005 force field, and energy was reduced as much as possible. The
Epik choice was made so that the ligand could remain in the correct protonation state
throughout the process.
2.7.2. DETERMINING PROTEIN BINDING REGIONS
We uploaded the three-dimensional crystal structure of the aromatase enzyme,
which may be found in the RCSB Protein Data Bank (PDB ID: 3S7S). The 3D crystal
structure has been fixed and prepared with the help of Maestro 12.5's protein
preparation wizard. To get started, the crystal structure had every last trace of water
vapor evaporated. The protein's bond orders and charges were determined before
any of the missing hydrogen atoms were added. Ionization of amino acids was
achieved through adjustment of the physiological pH via the Propka software. As a
final step, the OPLC force field was used for restrained minimization. For docking
purposes, this streamlined structure worked wonderfully. After protein preparation, the
best protein binding site was determined by identifying the highest-ranked potential
protein binding sites utilizing the use of the maestro 12.5 glide grid program.
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
92
2.7.3. MOLECULAR DOCKING INVESTIGATION
Binding sites on the receptor were located using the glide grid tool, and the best
ligand poses and binding energies were predicted using ligand docking. To begin, the
Glide docking module in Maestro 12.5 was used to successfully dock all ligands onto
their corresponding receptors. A grid box was generated using the receptor grid
generation platform in the region of the co-crystallized ligand that is favored at the
binding site. Maestro 12.5 was used to perform the simulations. Last but not least, the
maestro 12.5 work space visualizer was used to visualize poses and analyze the
resulting data.
3. RESULTS AND DISCUSSION
Synthetisesed Using Schiff bases of 1,3-dimethyl-6-(amino aceto hydrazine)
pyrimidine-2,4-dione-6-yl and various reagents, a series of new heterocyclic rings with
five members was synthesized Scheme-1. This series includes tetrazoline,
thiazolidin-4-one and imidazolidine-4-one.
+
CHO
EtOH
glu-CH
3
COOH
HSCH
2
COOH
H
2
NCH
2
COOH
ZnCl
2
/THF
THF
NaN
3
THF
G =
NO
2
Cl HO N(CH
3
)
2
, , ,
N
N
O
CH
3
O
CH
3
NH
H
NNH
2
O
N
N
O
CH
3
O
CH
3
NH
H
N
N
O
C
H
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
NH
G
G
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
HN
N
N
G
O
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
S
G
O
G
1-5
6-10 16-20
11-15
,
H
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
93
3.1. SCHEME-1 SYNTHESIS OF NEW TETRAZOLINE,
THIAZOLIDIN-4-ONE, AND IMIDAZOLIDINE-4-ONE
DERIVATIVES
The first step in the synthesis of new in Scheme-1 tetrazol, thiazolidin-4-one, and
imidazolidine-4-one derivatives. A solution of 1,3-dimethyl-6-(amino aceto hydrazine)
pyrimidine-2,4-dione-6-yl, para substituted aromatic aldehydes and absolute ethanol
Its solvents were thoroughly combined with glacial acetic acid a catalytic three drops
to synthesized Schiff bases derivatives (1-5) in table-1 showed the physical
properties and FTIR of compound (1-5). The FTIR spectrum[34]
showing in
figure(1-5) includes the presence of a ν(N-H) at (3301-3282) cm-1; ν(C-H) Arom. at
(3099-3001) cm-1; ν(C-H) Aliph. at (2997-2941) cm-1; ν(C=O) at (1731-1656) cm-1,
ν(C=N) at (1649-1627) cm-1 and ν(C=C) at (1625-1619) cm-1
of compound (1-5). The
compound (2) have ν(-NO2) in asym. at (1521 cm-1) and sym. at (1346 cm-1);
compound (3) have ν(C-Cl) at (1091 cm-1) and compound (4) have ν
(-OH) at (3433
cm-1). Compound (5) 1H-NMR spectra data, all signals shown in table-5 and showing
in Figure 21 that contain signal 2.51 (s, 6H, N-(CH3)2); 2.96 (s, 3H, N-CH3
); 2.99 (s,
3H, ); 3.4 (s, 1H, NH); 3.51 (s, 2H, CH2); 3.57 (s, 1H, =CH); 6.75 (s, 1H, N=C-
H); 7.63-8.49 (m, 4H, Ar-H); 9.66 (s, 1H, HN-N). Table-6 shows the 13C-NMR
spectrum data of this compound (5) and showing in Figure 22.
Synthisesed compounds (6-10) by cyclization compound (1-5) through sodium azide
in ethanol as solvent as showing in scheme-1. In table-2 showed the physical
properties and FTIR of compound (6-10). The FTIR spectrum
of tetrazoline
derivatives showing in figure(6-10) includes the presence of a ν
(N-H) at (3319-3275)
cm-1; ν(C-H) Arom. at (3077-3023) cm-1; ν(C-H) Aliph. at (2997-2923) cm-1; ν(C=O) at
(1711-1668) cm-1, ν(C=C) at (1625-1608) cm-1 and ν(N=N) at (1457-1448) cm-1of
compound (6-10). The compound (7) have ν(-NO2) in asym. at (1523 cm-1) and sym.
at (1346 cm-1); compound (8) have ν(C-Cl) at (1089 cm-1
) and compound (10) have
ν(-OH) at (3406 cm-1). Compound (7) 1
H-NMR spectra data, all signals shown in
table-5 and showing in Figure 23 that contain signal at 2.5 (s, 3H, N-CH3); 2.5 (s, 3H,
); 3.45 (s, 2H, CH2); 3.46 (s, 1H, NH); 3.56 (s, 1H, N-CH
tetrazoline ring);
3.62 (s, 1H, =CH); 4.9 (s, 1H, N-NH-N); 7.5-8.3 (m, 4H, Ar-H); 9.5 (s, 1H, HN-N).
Compounds (11-15) were synthesized by cyclizing compounds (1-5) through 2-
mercaptoacetic in THF as the solvent, as in Scheme-1. In table-3 showed the
physical properties and FTIR of compound (11-15). The FTIR spectrum of
Thiazolidin-4-one derivatives showing in figure(11-15) includes the presence of a
ν(N-H) at (3350-3253) cm-1; ν(C-H) Arom. at (3097-3002) cm-1; ν
(C-H) Aliph. at
(2983-2956) cm-1; ν(C=O) at (1733-1683) cm-1, ν(C=C) at (1628-1618) cm-1 and ν(C-
S) at (709-696) cm-1of compound (11-15). The compound (12) have ν(-NO2) in asym.
N
O O
CH
3
N
O O
CH
3
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
94
at (1521 cm-1) and sym. at (1346 cm-1); compound (13) have ν(C-Cl) at (1091 cm-1
)
and compound (14) have ν(-OH) at (3444 cm-1). Compound (13) 1
H-NMR spectra
data, all signals shown in table-5 and showing in Figure 24 that contain signal 2.5 (s,
3H, N-CH3); 2.5 (s, 3H, ); 3.58 (s, 2H, CH2); 3.83 (s, 2H, S-CH2
); 3.98 (s, 1H,
NH); 4.1 (s, 1H, N-CH thiazolidinone ring); 4.2 (s, 1H, =CH); 7.5-8.3 (m, 4H, Ar-H
);
8.7 (s, 1H, HN-N). Table-6 shows the 13
C-NMR spectrum data of this compound (13)
and showing in Figure 25.
Synthisesed compound (16-20) by cyclization compound (1-5) through glycine in
ethanol as solvent as in scheme-1. In table-4 showed the physical properties and
FTIR of compound (16-20). The FTIR spectrum
of imidazolidine-4-one derivatives
showing in figure(16-20) includes the presence of a ν(N-H) at (3298-3180) cm-1; ν(C-
H) Arom. at (3062-3049) cm-1; ν(C-H) Aliph. at (2995-2958) cm-1; ν
(C=O) at
(1731-1662) cm-1 and ν(C=C) at (1630-1610) cm-1
of compound (16-20). The
compound (17) have ν(-NO2) in asym. at (1521 cm-1) and sym. at (1344 cm-1
);
compound (18) have ν(C-Cl) at (1089 cm-1) and compound (19) have ν
(-OH) at (3413
cm-1). Compound (16) 1
H-NMR spectra data, all signals shown in table-5 and
showing in Figure 26 that contain signal 2.5 (s, 3H, N-CH3); 2.5 (s, 3H,
); 3.17
(s, 2H, CH2); 3.17 (s, 2H, CH2-NH); 3.38 (s, 1H, NH); 3.57 (s, 1H, N-CH
imidazolidinone ring); 3.59 (s, 2H, N-CH2); 3.64 (s, 1H, =CH); 7.5-8.3 (m, 4H, Ar-H
);
8.7 (s, 1H, HN-N).
N
O O
CH
3
N
O O
CH
3
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
95
Table 5. 1H-NMR of compound (5, 7, 13 and 16)
Table 6. 13C-NMR of compound (5 and 13)
No. Compound structure 1H-NMR spectral data (ᵟppm)
5
7
13
16
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
NH
O
2.5 (s, 3H, N-CH3); 2.5 (s, 3H,
); 3.45 (s, 2H, CH2); 3.46 (s,
1H, NH); 3.56 (s, 1H, N-CH
tetrazoline ring); 3.62 (s, 1H, =CH);
4.9 (s, 1H, N-NH-N); 7.6-8.4 (m, 4H,
Ar-H); 9.5 (s, 1H, HN-N)
N
O O
CH
3
2.5 (s, 3H, N-CH3); 2.5 (s, 3H,
); 3.58 (s, 2H, CH2); 3.83 (s,
2H, S-CH2); 3.98 (s, 1H, NH); 4.1 (s,
1H, N-CH thiazolidinone ring); 4.2 (s,
1H, =CH); 7.5-8.2 (m, 4H, Ar-H); 8.7
(s, 1H, HN-N)
N
O O
CH
3
2.51 (s, 6H, N-(CH3)2); 2.96 (s, 3H, N-
CH3); 2.99 (s, 3H, ); 3.4 (s,
1H, NH); 3.51 (s, 2H, CH2); 3.57 (s,
1H, =CH); 6.75 (s, 1H, N=C-H);
7.63-8.49 (m, 4H, Ar-H); 9.66 (s, 1H,
HN-N)
N
O O
CH
3
N
N
O
CH
3
O
CH
3
NH
H
N
N
O
C
H
N
CH
3
CH
3
N
N
O
CH
3
O
CH
3
NH
H
NN
O
H
C
HN
N
N
NO
2
2.5 (s, 3H, N-CH3); 2.5 (s, 3H,
); 3.17 (s, 2H, CH2); 3.17 (s,
2H, CH2-NH); 3.38 (s, 1H, NH); 3.57
(s, 1H, N-CH imidazolidinone ring);
3.59 (s, 2H, N-CH2); 3.67 (s, 1H,
=CH); 7.5-8.3 (m, 4H, Ar-H); 8.7 (s,
1H, HN-N)
N
O O
CH
3
N
N
O
CH3
O
CH3
NH
H
NN
O
H
C
S
Cl
O
No. Compound structure 13C-NMR spectral data (ᵟppm)
5
28.31 (C1, C3); 58.23 (C7); 65.03 (C5);
111.23 (C11); 112.35 (C12
); 129.97
(C10); 152.54 (C6, C9); 160.31 (C2, C4);
165.14 (C8)
13
28.31 (C1, C3); 38.23 (C10); 59.11 (C7);
61.13 (C11); 66.01 (C5); 129.18 (C13);
133.05 (C14); 136.17 (C12
); 138.26
(C15); 152.12 (C6); 160.06 (C2, C4);
166.93 (C8, C9)
N
N
O
H
3
C
O
CH
3
N
H
H
N
O
N
N
CH
3
CH
3
2 6
5
43
1
7
8
9
10
11
12
10
12
11
13
13
N
N
O
O N
H
H
N
O
N
S
Cl
O
2
6
5
43
1
7
8
11
12
9
10
13 14
15
1413
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
96
Figure 1. FTIR Soectrum of Compound (1)
Figure 2. FTIR Soectrum of Compound (2)
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
97
Figure 3. FTIR Soectrum of Compound (3)
Figure 4. FTIR Soectrum of Compound (4)
https://doi.org/10.17993/3ctic.2023.121.83-116
3C TIC. Cuadernos de desarrollo aplicados a las TIC. ISSN: 2254-6529
Ed.42 | Iss.12 | N.1 January - March 2023
98