Synthesis of novel 5-substituted imidazolinones as insecticides against cotton leaf worm (Spodoptera littoralis)

Article abstract of DOI:10.1002/jhet.3788

In the light of using of 5-imidazolinones in agriculture as safe and stable herbicides, the pesticide activities of some new synthesized derivatives 3-18 of this ring system against “cotton leaf worm (Spodoptera littoralis)” have been investigated. The in

Full text of DOI:10.1002/jhet.3788

Received: 22 April 2019
DOI: 10.1002/jhet.3788
Revised: 29 September 2019
Accepted: 7 October 2019
A R T I C L E
Synthesis of novel 5-substituted imidazolinones as
insecticides against cotton leaf worm (Spodoptera littoralis)
Mamdouh A. Sofan1
| Tarek M. Abou Elmaaty2
| Abdel-Kader M. Elkafafy3
|
Ahmed E. M. Abdel Mageed3
1Chemistry Department, Faculty of
Science, Damietta University, New
Damietta, Egypt
2Faculty of Applied Arts, Damietta
University, Damietta, Egypt
Abstract
In the light of using of 5-imidazolinones in agriculture as safe and stable herbi-
cides, the pesticide activities of some new synthesized derivatives 3-18 of this
ring system against “cotton leaf worm (Spodoptera littoralis)” have been inves-
tigated. The interpretation of the elemental and spectral analyses proved the
correct structural formulae of the new synthesized compounds. The com-
pounds 1, 5, 6a,b, 8a,c, 9, 11, 12, 15, 16, 17, and 18 showed higher potency
than chlorpyrifos (dursban) recommended insecticide. While the derivatives 2,
3, 4, 7, 8b, 10, 13, and 14 showed toxicity values less than chlorpyrifos insecti-
cide. The 5-imidazolinones 9 and 12 may be potentially used as insecticides for
treatment of cotton leaf worm.
3Plant Protection Research Institute,
Agriculture Research Centre, Giza, Egypt
Correspondence
Mamdouh A. Sofan, Chemistry
Department, Faculty of Science, Damietta
University, New Damietta 34517, Egypt.
Email: masofan1953@du.edu.eg
1 | INTRODUCTION
conducted on the efficacy and potential use of these
imidazolinones to weed control.[19,20] In the light of these
The significant biological importance of the 5-imidaz-
linones in the field of drugs and pharmaceuticals has been
described in the literatures. Many heterocyclic compounds
containing the 5-imidazolinone as central moiety are used
as antitubercular,[1] antihistamine,[2] antimicrobial,[3–5]
local anesthetic,[6] sedative and hypnotics,[7] anthel-
mintic,[8] antiviral agents.[9] Moreover, oxoimidazolines
which are also known as imidazolinones, were found to be
exceedingly effective as herbicidal, fungicidal, and vasodila-
tor and anticancer agents.[10–16]
The imidazolinone herbicides consist of six commer-
cial products (Figure 1) with varying levels of crop selectiv-
ity and herbicidal activity depending on the chemistry.[17]
Each compound of these herbicides is mainly considered
as derivative of the parent 2-(4-isopropyl-4-methyl-5-oxo-
4,5-dihydro-1H-imidazol-2-yl)nicotinic acid (or its benzoic
acid analog, which is present as a mixture of the m- and
p- isomers).[18]
facts, we report here our trial to explore a safe alternative
to harmful pesticides for the cotton leaf worm by synthe-
sis of some new derivatives of 5-imidazolinones. Insecti-
cides are currently the principle method for controlling
the Egyptian cotton leaf worm in Egypt and will continue
to be used until more biologically based management sys-
tems could be developed.[21] Also, this work is mainly
focused on the investigation of the toxicity of the synthe-
sized compounds against cotton leaf worm (Spodoptera
littoralis), and the mechanism of their action will require
further study which depends on determining the change
of the enzymes of the larvae.
2 | RESULTS AND DISCUSSION
2.1 | Chemistry
These herbicides are utilized in many different crops
and production of food and fiber because of their versatil-
ity, low toxicity, and environmental safety. Due to their
vital roles in agriculture, a great deal of research has been
The synthesis of imidazolin-5-one derivative 2 was car-
ried out by reacting of “4-benzylidene-2-phenyloxazol-
5(4H)-one” (1) with ammonium acetate in refluxing gla-
cial acetic acid. The oxazolinone 1 was prepared by
J Heterocyclic Chem. 2019;1–13.
wileyonlinelibrary.com/journal/jhet
© 2019 Wiley Periodicals, Inc.
1

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SOFAN ET AL.
FIGURE 1 The imidazolinone
herbicides; imazapyr (I), imazapic (II),
imazethapyr (III), imazamox (IV),
imazaquin(V), and imazamethabenzmethyl
(VI) it is present as a mixture of the m-and
p-isomers)
condensing hippuric acid with benzaldehyde, acetic
anhydride, and fused sodium acetate, based on the
method described in the literature.[22] The structure of
compound 2 has been assigned as a reaction product
based on analytical and spectral data, which were in full
agreement with the literature data.[23] The IR spectrum
showed the absorption bands of NH, C=O, and C=N
groups in imidazolinone ring at 3189, 1697, and
1639 cm−1, respectively. The “1H-NMR spectrum” rev-
ealed singlet signals at 7.032 and 8.162 ppm which were
attributed to benzal and NH protons, respectively.
2.032 and 3.524 ppm, respectively in the “1H-NMR spec-
tra”. In addition, “the IR spectrum of compound 5”
showed the absorption band of CN group at 2217 cm−1
(Scheme 1).
The nucleophilicity of methylene group of
3-oxopropanonitrile moiety in compound 5 towards aro-
matic aldehydes, nitrous acid, and diazonium salts was
studied. Thus, the compound 5 was condensed with
benzaldehyde and/or p-anisaldehyde in the presence of
piperdine (Knoevenagel reaction's conditions) to obtain
the arylidene derivatives 6a, b, respectively. The “1H-
NMR spectra” of compounds 6a, b showed the disappear-
ance of CH2 protons at 3.524 ppm and revealed a signal
of the methine's proton which interfered with aromatic
protons at δ 8.163-8.378 ppm. On the other hand, com-
pound 5 was treated with nitrous acid and/or diazonium
chlorides of aromatic amines to afford the derivatives
7 and 8, respectively. The “1H-NMR spectra” revealed
singlet signals at 11.523 ppm due to the OH proton in
compound 7, and 3.566 ppm of CH proton in 8a and dis-
appearance of singlet signals of CH2 protons at 3.524
ppm. While the signal of the arylidene proton (ArCH=C)
The reactivity of imidazole NH of “4-benzylidene-
2-phenyl-1H-imidazol-5(4H)-one”
(2)
towards
α-
haloketones was utilized to obtain the precursor 3 and
the reaction smoothly took place in DMF in the presence
of triethylamine at room temperature. Thus, the com-
pound 3 could be synthesized by treatment of compound
2 with chloroacetyl chloride under aforementioned con-
ditions. The IR spectrum of 3 showed a disappearance of
the NH absorption band at 3189 cm−1 and displayed a
new one at 1697 cm−1 which may be attributed to CO
function. The “1H-NMR spectrum” revealed a singlet sig-
nal at δ 4.102 due to the methylene group and disappear-
ance of NH singlet signal at δ 8.162 ppm.
in 6a is interfered in aromatic protons at
δ
8.163-8.378 ppm (Scheme 2).
1-(2-Chloroacetyl)-1H-imidazol-5(4H)-one derivative
3 was, in turn, heated with sodium azide and/or potas-
sium cyanide in DMF under reflux to afford the products
4 and 5, respectively. The correct elemental and spectral
analyses established the structural formulae of these
products. The signals of the two protons of both CH2
groups in compounds 4 and 5 appeared as singlet at δ
Multi component reactions (MCRs) attracted the
attention of many scientists because they are not difficult
to be carried out as the successive step syntheses. Tide
with high through put library, this policy had a signifi-
cant process in the drug discovery, in the context of rapid
identification and optimization of biologically active lead
compounds. So, we have synthesized thieno derivatives

SOFAN ET AL.
3
SCHEME 1 General synthesis of
1-chloroacetyl, 1-azidoacety, and
1-cyanoacetylimidazolinones
SCHEME 2 General synthesis of
imidazolinone derivatives 6-8
SCHEME 3 Synthesis of compounds
9 and 10
9 and 10 by employing the MCRs strategy (under Gewald
reaction's conditions). The reactions were performed by
heating the precursor 5 under reflux with sulphur ele-
ment, ethyl acetoacetate and/or cyclohexanone in
ethanolic piperidine. The chemical structure of com-
pound 9 was confirmed by “IR spectrum,” which showed
absorption bands at 3355 and 1716 cm−1 due to the NH2
and C=O groups. The “1H-NMR spectrum” of compound
9 exhibited a singlet signal at δ 2.340 corresponding to
methyl group and the signals of ethyl group at 1.278 and
4.301 ppm. The structure of 10 was established according
to the “1H-NMR spectrum” which showed multiplet sig-
nal of the CH2 groups of the cyclohexene moiety at
1.231-1.360 ppm and the presence of NH2 band at
3319 cm−1 in the IR spectrum (Scheme 3).
Moreover, the imidazolinones (11-15) have been pre-
pared by reaction of oxazolone 2 with different amines
namely “2-aminothiazole, 3-amino-1,2,4-triazole, 4-amino-
antipyrine, p-aminoacetophenone, and benzocaine,”
respectively (Scheme 4).
The chemical structures of these imidazolinone deriva-
tives were established by the analytical and spectroscopic

4
SOFAN ET AL.
SCHE ME 4 Synthesis of
imidazolinones 11-15
SCHE ME 5 Synthesis of
compounds 16-18
methods. For example, the structure formula of 15 was
confirmed by IR spectrum, which exhibited a new band at
1690 cm−1 due to the ester group and the disappearance of
the C=O lactone absorption band at 1715 cm−1. The “1H-
NMR spectrum” of compound 15 showed a new quartet
signal at δ 4.30 and triplet signal at δ 1.32 corresponding to
the ethyl ester. The molecular ion peak of 15, which is
corresponding to a molecular formula C24H19N2O3
appeared at m/z = 396 in “the mass spectrum chart.”
The ethyl 1H-imidazol-1-yl benzoate derivative 15 was
condensed with thiosemicarbazide and/or hydrazine
hydrate in ethanol under reflux to give the expected
benzoylhydrazine carbothioamide (16) and hydrazide (17)
derivatives in good yield, respectively. The structure for-
mula of compound 16 was proved by “1H-NMR spectrum,”
which revealed three singlet signals at δ 9.31 and 10.51 due
to NH and NH2, in addition to the signal of NH proton that
is contaminated with the aromatic proton at δ 7.86-8.03,
respectively. In turn, the hydrazide 17 was condensed under
reflux with ethyl cyanoacetate in ethanol to obtain the 1H-
imidazol-1-yl-N'-(2-cyanoacetyl) benzohydrazide deriva-
tives (18). The correct chemical structure of compound 18
was estimated by different analytical and spectroscopic
data. The “IR spectrum” displayed a new absorption bands

SOFAN ET AL.
5
TABLE 1 Susceptibility of “second instar larvae of the cotton leaf worm, S. littoralis” to tested compounds 2-11
LC50 (ppm)
LC90 (ppm)
Tested compounds
2
Its limits at 95%
Its limits at 95%
Slope
Toxicity index %
2129.05
5303.48
3.233 0.650
25.92
1711.27 3225.11
3413.45 19 612.13
3
924.18
623.65 1421.10
4687.16
2492.46 26 908.17
1.818 0.35
2.46 0.37
1.39 0.33
1.74 0.34
1.85 0.45
1.38 0.33
1.85 0.34
2.33 0.55
2.05 0.35
2.10 0.35
1.97 0.36
1.27 0.26
59.71
53.92
68.38
94.83
88.66
53.38
73.90
55.61
69.98
100.00
54.36
64.42
4
1023.36
655.99 1359.39
3690.31
2402.58 12 107.74
5
807.08
443.62 1402.14
6714.75
2809.34 20 369.62
6a
581.94
325.65 846.23
3147.19
1797.73 14 267.55
6b
622.42
180.19 923.32
3046.04
1910.66 16 454.86
7
1033.72
626.92 2139.41
8722.66
3336.83 46 142.04
8a
746.71
475.55 1074.34
3648.14
2074.01 15 905.24
8b
992.40
622.30 1387.93
3519.82
2131.48 22 540.10
8c
788.62
539.24 1110.29
3320.28
2008.82 10 970.62
9
551.89
344.45 760.34
2246.52
1457.04 5781.09
10
1015.17
715.00 1537.63
4517.13
2512.39 20 813.01
Chlorpyrifos
856.61
13418.05
498.70 2715.78
3703.24 423 941.62
Note: Toxicity index = (LC50 of the most effective compound/LC50 of the tested compound) × 100.
at 2220, 3160, and 3210 cm-1 due to CN and 2NH, respec-
tively. The “1H-NMR spectrum” showed three singlet sig-
nals at δ 3.98, 8.80, and 9.55 corresponding to cyanomethyl
and 2NH, respectively. The “mass spectrum” showed a
molecular ion peak at m/z = 449 due to a molecular for-
mula C25H19N5O3 (Scheme 5).
of “25 1ꢀC and 70 5% RH” and keeping off any con-
tamination by chemicals till the time of study.[24] Egg
masses were provided from “Plant Protection Research
Institute, Dokki, Giza”. Egg-masses were placed on leaves
of caster bean; Ricinus communis L., on cylindrical glass
jars (11b), which were covered with muslin cloth held
with a rubber band. After hatching of the egg, the first
instar larvae were transferred into larger rearing jars
(41b) containing filter papers at its bottom to absorb the
excess of moisture. Larvae reared on fresh castor bean
leaves, which were provided daily in sufficient amounts.
The accumulative fasces and debris were cleaned out
daily. Towards the end of the sixth instar larvae, moist
sawdust was placed at the base of the rearing jars to pro-
vide a pupation site. Eventually, the formed pupae were
collected and left in clean jars until adult's emergence.
The newly emerged moths were provided with 10%
honey solution absorbed in cotton wool, which was
placed in plastic cup for moth feeding. The fermentation
and growth of microorganisms could be avoided by daily
2.2 | Insecticidal activity
2.2.1 | Methods
Bioassay test for the new selected compounds was carried
out in plant protection research institute—Mansoura
branch, Agriculture research Center.
Tested insect
The susceptible and homogeneous strain could be
obtained by maintaining the laboratory strain of cotton
leaf worm S. littoralis (Boisd.) under constant conditions

6
SOFAN ET AL.
TABLE 2 Susceptibility of “second instar larvae of the cotton leaf worm, S. littoralis” to tested compounds 1 and 12-19
LC50 (ppm)
LC90 (ppm)
Tested compounds
1
Its limits at 95%
Its limits at 95%
Slope
Toxicity index %
654.25
3239.47
1.84 0.34
45.86
401.36 938.60
1884.12 13 047.13
11
470.96
255.71 682.87
2070.42
1222.73 4169.18
1.99 0.42
1.14 0.26
1.46 0.34
1.43 0.33
1.75 0.41
1.77 0.34
1.57 0.33
1.57 0.33
1.27 0.26
63.71
100.00
29.36
32.13
64.19
38.86
38.22
38.22
35.02
12
300.07
99.64 469.08
1625.58
1020.66 5325.38
13
1021.99
637.97 1953.39
7649.12
3161.86 20 778.75
14
933.69
559.59 1718.60
7342.02
3033.81 21 530.97
15
467.45
215.89 710.5
2520.70
1348.06 25 574.65
16
772.00
491.97 1145.43
4052.95
2211.54 21 330.47
17
785.08
467.73 1243.43
5120.06
2480.53 52 599.79
18
785.08
467.73 1243.43
5120.06
2480.53 52 599.79
Chlorpyrifos
856.61
13418.05
498.70 2715.78
3703.24 423 941.61
Note: Toxicity index = (LC50 of the most effective compound/LC50 of the tested compound) ×100.
renewing of the honey solution. As an oviposition site,
fresh green leaves of Dalfa, Nerium oleander L., were
daily introduced into the breading cases. The newly laid
egg-masses were collected daily and transferred into the
rearing jars (five egg-masses/jars). All rearing cases and
jars were placed under laboratory condition of 28 + 2ꢀC
and 65 5% RH.[24] The progeny of these insects together
with occasional fresh supplies of egg, formed the basis of
a culture designed to provide insects used in the present
investigation. The test was carried out using the second
instar of larvae.
instar larvae of S. littoralis” occurred by the “the leaf dip
technique”.[25] In this technique, the emulsions of the
synthesized compounds in water containing 0.1% triton
X-100 were prepared and immediately used. Four repli-
cates (each of 10 larvae) were tested for each concentra-
tion for larvicidal action. After dipping in each
concentration for 30 seconds, the fresh caster-bean leaves
must be dried in shade before offered to the larvae. The
larvae were allowed to feed on the treated leaves for 24 h.
Test also included the control treatment in which the
leaves were similarly dipped in a solution of water plus
0.1% Triton X-100. Then, the mortality percentages were
recorded after 24 hours from the daily inspection for all
treatments. The mortality percentage of the control
experiment is zero%. The average of mortality percentage
was recorded using Abbott formula.[26] % mortality = (C
−T/C) × 100 (C is the number living in the control; T is
the percent living in the treated). The corrected mortality
percentage of each compound was statically computed
according to Finney,[27] from which the corresponding
concentration probit lines (LC-p lines) were estimated to
determine the LC50 and LC90 values of tested compounds.
The slope values of the tested compounds were also cal-
culated. In addition, the efficacy of different compounds
was measured by comparing the tested compounds with
Preparation of the concentration to be tested
A known weight of the new 5-imidazolinone derivative
was dissolved in a least volume of the solvent to obtain a
stock solution. For more homogeneity, a 0.1% of triton X-
100 was added to the first dilution of this stock solution.
Successive dilutions were carried out for the latter solu-
tion to obtain a series of different concentrations (2000,
1500, 1000, 500, and 250 ppm) for each synthesized
compound.
Leaf dipping technique
The experiments that used to study the toxicity of the
5-imidazolinone derivatives (1-18) against “the second

SOFAN ET AL.
7
the most effective compound using the following equa-
tion[28]; toxicity index = (LC50 of the most effective com-
pound/LC50 of the tested compound).
analyses were ascertained on a “PERKIN-ELMER 2400 C,
H, N elemental analyzer, Cairo University,” (PERKIN-
ELMER, MA) and mass spectra were determined by
“Shimadzu QP-2010 Plus apparatus” (Shimadzu, Kyoto,
Japan). An analytical TLC on the precoated glass plate (sil-
ica gel 60 F254-plate-Merck; Darmstadt, Germany) was uti-
lized to monitor the reaction's progress and the products
were visualized by UV light.
Results of insecticidal activity
The results of our investigation of the susceptibility of a lab-
oratory strain of “the second instar larvae of the cotton leaf
worm S. littoralis (Boisd.)” to “4-benzylidene-2-phenyl-1H-
imidazol-5(4H)-one (2)” and its derivatives (3-18) were
explained in Tables 1 and 2. Data indicated that compounds
12 and 9 were approved to be the most potent compounds
in this group with LC50 values of 300.07 and 551.89 ppm
than chlorpyrifos. Also, compounds 15, 11, 6a, 6b, and
1 have nearly the same range of activity, which is higher
than chlorpyrifos activity. The toxicity values of compounds
8a, 16, 17, 18, 8c and 5 are still higher than chlorpyrifos'
value. The parent compound 2 and its derivatives 3, 14, 8b,
10, 13, 4, and 7 showed potent activities less than chlorpyri-
fos insecticide, respectively.
4.1 | Synthesis of 4-benzylidene-
2-phenyloxazol-5(4H)-one (1)
“4-benzylidene-2-phenyloxazol-5(4H)-one”
(1)
was
obtained by the method described in Ref.[[22]].
4.2 | Synthesis of compound 2
The solution of oxazolinone derivative 1 (2.49 g, 0.01 mol)
and ammonium acetate (1.54 g, 0.02 mol) in glacial acetic
acid (15 mL) was heated under reflux for 4 h. The reaction's
flask was left to stand at a normal temperature for over-
night. The yellow solid material was filtered off, dried in air
and recrystallized from ETOH to give the product 2.[23]
3 | CONCLUSION
In the light of versatility, low toxicity and environmental
safety of imidazolinone herbicides, a number of new
5-imidazolinone derivatives could be synthesized in trial
to explore a safe alternative to harmful pesticides for cot-
ton leaf worm. Therefore, the new compounds (3-18)
were synthesized and their structural formulae were
characterized by the correct elemental and spectral ana-
lyses. The results of the treatment of cotton leaf worm S.
littoralis (Boisd.) with these derivatives (1-18) in compari-
son with the chlorpyrifos insecticide could be summarized
in two groups. The first group consists of 13 compounds
namely, 1, 5, 6a,b, 8a,c, 9, 11, 12, 15, 16, 17, and 18 which
showed higher potency than chlorpyrifos. This group of
new 5-imidazolinones, especially 12 and 9 may be poten-
tially used as stable insecticides for treatment of cotton
leaf worm. While the second group, which contains seven
compounds (2, 3, 4, 7, 8b, 10, 13, and 14) showed toxicity
values less than chlorpyrifos.
4.2.1 | 4-benzylidene-2-phenyl-1H-
imidazol-5(4H)-one (2)
Yield 69%, yellow crystals, mp > 300ꢀC; IR: 3189 (NH),
1
1697 (CO), 1639 (C=N), 1597 (C=C) cm−1; H-NMR: δ
7.032 (s, 1H, CH), 7.472-7.497 (m, 5H, ArH), 7.599-7.632 (m,
5H, ArH), 8.162 (s, 1H, NH) ppm; 13C NMR:
116.1(PhHC=C<), 125.9, 128.3, 128.8, 135.2 (benzylidene
C6), 129.6, 129.9, 132.9, 133.4 (phenyl C6), 130.9, 161.8,
172.9 (imidazoline C3) ppm; MS: m/z 248.13 (100%), 117.
09 (46%), 104.08 (54%); Anal. calcd for C16H12N2O (248): C,
77.4; H, 4.84; N, 11.29%; found: C, 77.36; H, 4.69; N, 11.31%.
4.3 | Synthesis of compound 3
4 | EXPERIMENTAL
The triethylamine (1 mL) was added to the solution of
compound 2 (2.48 g, 0.01mol) in DMF (15 mL). After
cooling to 0ꢀC in crushed ice, 2-chloroacetyl chloride
(1.12 g, 0.01 mol) was gradually added to this reaction
mixture with stirring. The stirring was continued for
3 hours at room temperature, and the reaction mixture
was, then, poured into ice cold water (50 mL). The yellow
solid precipitate was collected by filtration. It was left to
dry in air and then, purified by recrystallized from etha-
nol (95%) to give compound 3.
The “digital Gallen Kamp apparatus” was used to measure
the melting points. “Thermo Fisher Nicolete IS 10 FTIR IR
Spectrophotometer” (Thermo Fisher, MA) recorded the
infrared spectra on an in KBr disks (υ max in cm−1). The
NMR spectra (DMSO-d6) were obtained using “Bruker WP
300-MHz Spectrometer,” (Bruker, MA) the chemical shift
values were expressed in δ values (ppm) relative to that of
the solvent, and TMS was the internal reference. Elemental

8
SOFAN ET AL.
4.3.1 | 4-benzylidene-1-(2-chloroacetyl)-
2-phenyl-1H-imidazol-5(4H)-one (3)
evaporator. After cooling to room temperature, 10 mL of
cold water was added to triturate the residue. The solid
substance was filtered off, dried, and recrystallized from
ethanol to give the product 5.
Yellow crystals; yield 79%; mp 185ꢀC; IR 1697 (CO),1639
(C=N), 1597 (C=C) cm−1; 1H-NMR: δ 4.102 (s, 2H, CH2),
7.033 (s, 1H, CH), 7.429-7.519 (m, 3H, ArH), 7.576-7.652
(m, 3H, ArH), 8.165-8.197 (m, 2H, ArH), 8.328-8.333 (m,
2H, ArH) ppm; 13C-NMR: δ 42.01(CH2Cl), 116.50
(PhHC=C<), 128.02, 128.84, 127.90, 131.21 (C6H5),
128.49, 128.62, 127.88, 135.23 (C6H5), 130.34 (HC=C<),
156.91 (N-C=N), 167.51 (CO), 171.93 (CO) ppm; Anal.
calcd for C18H13N2O2Cl (324.5): C66.57; H, 4.03; N,
8.63%; found: C, 66.46; H, 4.19; N, 8.71%.
4.5.1 | 3-(4-benzylidene-5-oxo-2-phenyl-
4,5-dihydro-1H-imidazol-1-yl)-
3-oxopropanenitrile (5)
Yellow crystals; yield 82%; mp 225ꢀC; IR: 2217(CN), 1714
1
(CO), 1699 (CO), 1612 (C=C, C=N) cm−1; H-NMR: δ
3.524 (s, 2H, CH2), 7.031 (s, 1H, CH), 7.468-7.632 (m, 6H,
ArH), 8.163-8.330 (m, 6H, ArH) ppm; 13C-NMR: δ 22.03
(CH2CN), 116.50 (PhHC=C<), 120. 98 (CN), 128.02,
128.84, 127.90, 131.21 (C6H5), 128.49, 128.62, 127.88,
135.23 (C6H5), 130.34 (HC=C<), 156.91 (N-C=N), 169.15
(CO), 171.93 (CO) ppm; MS: m/z: 317.01 (12%), 275.00
(14%), 248.06 (48%), 144.02 (20%), 117.08 (62%), 103.96
(100%), 76.93 (98%); Anal. calcd for C19H13N3O2 (315): C,
72.37; H, 4.16; N, 13.33%; found: C, 71.50; H,
4.21; N, 13.21%.
4.4 | Synthesis of compound 4
Sodium azide (0.65g, 0.01mol) was added in small por-
tions to the solution of 3 (3.24 g, 0.01mol) in DMF
(15 mL) with stirring within 30 min. Heat the reaction
mixture for 8 hours under reflux. The solvent was
removed in a rotatory evaporator under vacuum. After
cooling to room temperature, triturate the residue with
cold water (10 mL). The yellow solid was filtered off, left
to dry in air, and purified by recrystallizing in ethanol to
give the product 4.
4.6 | Preparation of compounds 6a,b
In a round bottom flask (50 mL), compound 5 (3.15 g,
0.01 mol) was dissolved in 30 mL EtOH,1 mL of
pipredine was added followed by “benzaldehyde (1.06
g, 0.01mol) and/or p-anisaldehyde (1.36 g, 0.01 mol)”.
Heat the reaction mixture under reflux for 8h. Concen-
trate the solvent in rotatory evaporator under vacuum.
Leave the reaction mixture for one day at 0-5ꢀC to
complete precipitation of the solid product. This solid
was collected by filtration, dried in air and purified by
recrystallization from ethanol to yield compounds 6a
and 6b, respectively.
4.4.1 | 1-(2-azidoacetyl)-4-benzylidene-
2-phenyl-1H-imidazol-5(4H)-one (4)
Yellow green crystals; yield 80%; mp 190ꢀC; IR: 1701
(CO), 1667 (CO), 1641 (C=N), 1599 (C=C) cm−1 1H-
;
NMR: δ 2.032 (s, 2H, CH2), 7.032 (s, 1H, CH), 7.431-7.497
(m, 3H, ArH), 7.593-7.624 (m, 3H, ArH), 8.163-8.195 (m,
2H, ArH), 8.305-8.333 (m, 2H, ArH) ppm; 13C-NMR: δ
53.22 (CH2), 116.50 (PhHC=C<), 128.02, 128.84, 127.90,
131.21 (C6H5), 128.49, 128.62, 127.88, 135.23 (C6H5),
130.34 (HC=C<), 156.91 (N-C=N), 169.72 (CO), 171.93
(CO) ppm; MS: m/z 333.42 (48%), 314.04 (44%), 279.35
(26%), 270.14 (20%), 241.90 (42%), 217.27 (30%), 107.16
(100%), 104.87 (98%); Anal. calcd for C18H13N5O2
(331): C, 65.25; H, 3.95; N, 21.14%; found: C, 66.50; H,
3.91; N, 21.21%.
4.6.1 | 2-(4-benzylidene-5-oxo-2-phenyl-
4,5-dihydro-1H-imidazole-1-carbonyl)-
3-phenylacrylonitrile (6a)
Yellow crystals; yield 66%; mp 165ꢀC; IR: 2213(CN),
1
1717 (CO), 1638 (C=N), 1612 (C=C) cm−1; H-NMR: δ
7.031 (s, 1H, CH), 7.472-7.727 (m, 9H, ArH),
8.163-8.378 (m, 7H, ArH+ CH=) ppm; 13C-NMR:
δ105.82 (CN-C=CH), 113.50 (CN), 116.50 (PhHC=C<),
128.02, 128.84, 127.90, 131.21 (C6H5), 128.49, 128.62,
127.88, 135.23 (C6H5), 127.75, 128.09, 130.99, 131.87
(C6H5), 130.34 (HC=C<), 144.97 (CN-C=CH-Ph),
156.91 (N-C=N), 169.15 (CO), 171.93 (CO) ppm; MS:
m/z 405.23 (M++2, 4%), 310 (10%), 247.75 (24%),
4.5 | Synthesis of compound 5
After gradual addition of potassium cyanide (0.65 g, 0.01
mol) to the solution of 3 (3.24 g, 0.01 mol) in DMF
(15 mL) with stirring for 30 min, the reaction mixture
was boiled for 10 hours under reflux. The solvent was
concentrated under reduced pressure in rotatory

SOFAN ET AL.
9
117.17 (24%), 104.11 (100%), 91.89 (20%); Anal. calcd
for C26H17N3O2 (303): C, 77.4; H, 4.25; N, 10.24%;
found: C, 77.60; H, 4.21; N, 10.31%.
(344): C, 66.28; H, 3.51; N, 16.27%, found: C, 66.23; H,
3.47; N, 16.24%.
4.8 | Synthesis of compounds 8a-c
4.6.2 | 2-(4-benzylidene-5-oxo-2-phenyl-
4,5-dihydro-1H-imidazole-1-carbonyl)-
3-(4-methoxyphenyl)acrylonitrile (6b)
In a conical flask (100 mL), the mixture of precursor
5 (3.15g, 0.01 mol) and sodium acetate (3g, 0.3 mol) in
dioxane (30 mL) was magnetically stirred at 0ꢀC.
“1-chloro-2-phenyldiazene (1.4 g, 0.01 mol), 1-chloro-
2-(2-methoxyphenyl) diazene (1.7 g,0.01 mol), and/or
1-chloro-2-(2-nitrophenyl) diazene (1.85 g, 0.01 mol)”
was gradually added, followed by 4 mL of conc HCl. After
stirring in an ice bath for 10 h, the reaction mixture was
left in refrigerator to complete the precipitation of the
product (one day). The precipitate formed was filtered
and recrystallized from EtOH and drops of DMF to afford
8a-c.
Yellow crystals; yield 69%; mp 170ꢀC; IR: 2222(CN), 1716
1
(CO), 1638 (C–N), 1613 (C=C), 1596 (C=C) cm−1; H-
NMR: δ 3.316 (br, 3H of OCH3 + solvent), 7.031 (s, 1H,
CH), 7.498-7.651 (m, 9H, ArH), 8.220-8.380 (m, 5H, ArH
+ CH) ppm; 13C-NMR: δ 55.50 (CH3), 105.82 (CN-
C=CH), 113.50 (CN), 116.50 (PhHC=C<), 128.02, 128.84,
127.90, 131.21 (C6H5), 128.49, 128.62, 127.88, 135.23
(C6H5), 110.75, 122.01, 129.58, 157.89 (C6H4-OCH3),
130.34 (HC=C<), 144.97 (CN-C=CH-Ph), 156.91 (N-
C=N), 169.15 (CO), 171.93 (CO) ppm; MS: m/z 435.42
(M+ + 2, 4%), 302.18 (18%), 248.11 (8%), 117.09 (36%),
105.08 (100%), 91.09 (40%); Anal. calcd for C27H19N3O3
(433): C, 74.81; H, 4.42; N, 9.89%; found: C, 74.60; H,
4.21; N, 9.71%.
4.8.1 | 3-(4-benzylidene-5-oxo-2-phenyl-
4,5-dihydro-1H-imidazole-1-yl)-
2-(phenyldiazenyl)propanenitrile (8a)
Yellow crystals; yield 59%; mp 190ꢀC; IR: 2210(CN), 1716
1
4.7 | Synthesis of compound 7
(CO), 1638 (C=N), 1614 (N=N), 1594 (C=C) cm−1; H-
NMR: δ 3.566 (s, 1H, CH), 7.030 (s, 1H, CH), 7.527-7.740
(m, 9H, ArH), 8.213-8.372 (m, 6H, ArH) ppm; 13C-NMR:
δ106.82 (CN-C=N), 109.40 (CN), 116.50 (PhHC=C<),
128.02, 128.84, 127.90, 131.21 (C6H5), 128.49, 128.62,
127.88, 135.23 (C6H5), 112.43, 120.22, 124.09, 141.87
(C6H5), 130.34 (HC=C<), 156.91 (N-C=N), 165.15 (CO),
171.93 (CO) ppm; MS: m/z 421.66 (M++ 2, 4%), 272.49
(82%), 241.02 (28%), 189.47 (20%), 143.82 (36%), 113.82
(46%), 104.02 (76%), 77.03 (100%); Anal. calcd for
C25H17N5O2 (419): C, 71.59 H, 4.09; N, 16.70%, found: C,
71.55; H, 4.05; N, 16.66%.
A solution of compound 5 (3.15 g, 0.01 mole) in dioxane
(20 mL) containing conc. HCl (1.5 mL) was cooled to
0ꢀC. Ice-cold solution of NaNO2 (1.04 g, 0.015 mol) in
H2O (5mL) was carefully added at 0-5ꢀC with stirring.
The reaction mixture was left overnight in refrigerator.
The precipitate formed was filtered, washed with ice-cold
water (15 mL) and then with ethanol (5 mL). The yellow
solid was dried and recrystallized from ethanol to afford
compound 7.
4.7.1 | 2-(4-benzylidene-5-oxo-2-phenyl-
4,5-dihydro-1H-imidazole-1-yl)-N-hydroxy-
2-oxoacetimidoylcyanide (7)
4.8.2 | 3-(4-benzylidene-5-oxo-2-phenyl-
4,5-dihydro-1H-imidazole-1-yl)-
2-(2-methoxy phenyl diazenyl)-
3-oxopropanenitrile (8b)
Yellow crystals; yield 60%; mp 180ꢀC; IR: 3446 (OH),
2219 (CN), 1715 (CO), 1615 (C=N), 1599 (C=C) cm−1
;
1H-NMR: δ 7.523-7.737 (m, 7H, ArH + CH), 8.258-8.364
(m, 4H, ArH), 11.523 (s, 1H, OH) ppm; 13C-NMR: δ 113.9
(CN), 116.50 (PhHC=C<), 118.91 (C=NOH), 128.02,
128.84, 127.90, 131.21 (C6H5), 128.49, 128.62, 127.88,
135.23 (C6H5), 130.34 (HC=C<), 156.91 (N-C=N), 163.15
(CO), 171.93 (CO) ppm; MS: m/z 346.94 (M++2, 8%),
248.02 (10%), 273.19 (46%), 139.28 (30%), 118.76 (62%),
104.18 (100%), 77.30 (98%); Anal. calcd for C19H12N4O3
Yellow crystals; yield 55%; mp 179ꢀC; IR: 2217 (CN),
1715 (CO), 1638 (C=N), 1613 (N=N), 1995 (C=C) cm−1
;
1H-NMR: δ 3.597 (s, 1H, CH), 3.899 (s, 3H, OCH3), 7.026
(s, 1H, CH), 7.469-7.739 (m, 8H, ArH), 8.181-8.370 (m,
6H, ArH) ppm; 13C-NMR: δ 54.93 (OCH3),106.82 (CN-
C=N), 109.40 (CN), 116.50 (PhHC=C<), 128.02, 128.84,
127.90, 131.21 (C6H5), 128.49, 128.62, 127.88, 135.23
(C6H5), 114.24, 120.08, 122.09, 131.88, 145.61 (C6H4),

10
SOFAN ET AL.
130.34 (HC=C<), 156.91 (N-C=N), 165.15 (CO), 171.93
(CO) ppm; Anal. calcd C26H19N5O3 (449): C, 69.48 H,
4.26; N, 15.58%, found: C,69.43; H, 4.21; N, 15.53%.
(6%), 313.87 (10%), 273.96 (34%), 248.81 (10%), 219 (38%),
104.05 (98), 76.89 (100); Anal. calcd for C25H23N3O4S
(461): C, 65.06; H, 5.02; N, 9.10%, found: C, 65.00; H,
5.05; N, 9.15%.
4.8.3 | 3-(4-benzylidene-5-oxo-2-phenyl-
4,5-dihydro-1H-imidazole-1-yl)-
2-(2-nitrophenyl diazenyl)-
4.9.2 | 3-(2-amino-4,5,6,7,-
tetrahydrobenzo[b]thiophene-3-carbonyl)-
5-benzylidene-2-phenyl-3,5-dihydro-4H-
imidazol-4-one (10)
3-oxopropanenitrile (8c)
Yellow crystals; yield 55%; mp 182ꢀC; IR 2217 (CN), 1717
1
(CO), 1639 (C=N), 1615 (N=N), 1595 (C=C) cm−1; H-
Red crystals; yield 60%; mp 230ꢀC; IR: 3319 (NH2), 1705
NMR: δ 3.505 (s, 1H, CH), 7.026 (s,1H, CH), 7.493-7.663
(m, 8H, ArH), 8.223-8.364 (m, 6H, ArH) ppm; 13C-NMR:
δ 106.82 (CN-C=N), 109.40 (CN), 116.50 (PhHC=C<),
128.02, 128.84, 127.90, 131.21 (C6H5), 128.49, 128.62,
127.88, 135.23 (C6H5), 115.32, 120.01, 121.01, 131.98,
136.02, 140.10 (C6H4), 130.34 (HC=C<), 156.91 (N-C=N),
165.15 (CO), 171.93 (CO) ppm; MS: m/z 466.22 (M++ 2),
289.14 (100%), 271.14 (36%), 243.26 (20%), 189,22 (20%),
77.11 (70%); Anal. calcd for C25H16N6O4 (464): C,
64.65; H, 3.47; N, 18.10%, found: C, 64.60; H,
3.42; N, 18.05%.
(CO), 1699 (CO), 1638 (C=N), 1597 (C=C) cm−1 1H-
;
NMR: δ 1.231-1.360 (m, 8H, 4CH2), 7.031 (s, 1H, CH),
7.472-7.633 (m, 8H, ArH + NH2), 8.162-8.332 (m, 4H,
ArH) ppm; 13C-NMR: δ 23.00, 23.00, 23.39, 24.46 (CH2
cyclohexane), 116.50 (PhHC=C<), 128.02, 128.84, 127.90,
131.21 (C6H5), 128.49, 128.62, 127.88, 135.23 (C6H5),
115.33, 123.86, 140.01, 161.09, (C4S), 130.34 (HC=C<),
156.91 (N-C=N), 165.15 (CO), 171.93 (CO) ppm; MS: m/z
431.33 (M+ + 4,6%), 361.75 (56%), 248.08 (80%), 194.61
(20%), 117.66 (100%), 89.63 (90%); Anal. calcd for
C25H21N3O2S (427): C, 70.24; H, 4.95; N, 9.83%, found: C,
7.20; H, 4.90; N, 9.79%.
4.9 | Synthesis of compounds 9 and 10
4.10 | Preparation of compounds 11-15
Ethyl acetoacetate (1.30 g, 0.01 mol) and/or cyclohexa-
none (0.98 g, 0.01 mol) and sulphur (0.32 g, 0.01 mol)
were added, followed by 1 mL of piperidine to the
solution of compound 5 (3.15 g, 0.01 mol) in 30 mL
absolute ethanol with stirring. After reflux the reaction
mixture for 9h, it was left at room temperature over-
night. The red precipitate was filtered, dried in atmo-
spheric air, and crystallized from ethanol to get the
target compounds.
A
mixture of compound 1 (2.49 g, 0.01 mol),
“2-aminothiazole (1.00 g, 0.01 mol), 3-amino-1,-
2,4-triazole (0.84 g, 0.01 mol), 4-aminoantipyrine (2.03 g,
0.01 mol), p-aminoacetophenone (1.35 g, 0.01 mol),
and/or benzocaine (1.65 g, 0.01 mol)" was refluxed at
150-160ꢀC for 40-50 min in an oil bath. The mixture was
triturated with 20 mL of ethyl alcohol (95%), after leaving
to cool at room temperature. The solid product was col-
lected, dried, and crystallized from ethyl alcohol (95%) to
give the target compound.
4.9.1 | Ethyl 5-amino-4-(4-benzylidene-
5-oxo-2-phenyl-4,5-dihydro-1H-imidazole-
1-carbonyl)-3-methylthiophene-
2-carboxylate (9)
4.10.1 | 5-benzylidene-2-phenyl-
3-(thiazol-2-yl)-3,5-dihydro-4H-imidazol-
4-one (11)
Red crystals; yield 60%; mp 215ꢀC; IR: 3355 (NH2), 1716
1
(CO), 1695 (CO), 1611 (C=N, C=C) cm−1; H-NMR: δ
Pale yellow crystals; yield 75%; mp 175ꢀC; IR 1793 (CO),
1
1.276 (t, 3H, J=6.9 Hz, CH3CH2), 2.340 (s, 3H, CH3),
4.301 (q, 2H, J= 6.9 Hz, CH3CH2), 7.030 (s, 1H, CH),
7.58-7.73 (m, 12H, ArH+ NH2) ppm; 13C-NMR: δ 10.30
(CH3), 27.01 (CH3CO), 116.50 (PhHC=C<), 128.02,
128.84, 127.90, 131.21 (C6H5), 128.49, 128.62, 127.88,
135.23 (C6H5), 116.33, 140.11, 162.09, 174.99 (C4S), 130.34
(HC=C<), 156.91 (N-C=N), 165.15 (CO), 171.93 (CO),
187.34 (CO) ppm; MS: m/z 463.79 (M+ + 2), 6%), 365.01
3136 (NH) cm−1; H-NMR δ 7.23 (s, 1H, CH), 7.23-7.68
(m, 11H, ArH), 8.13 (d, 1H, J = 8.4 Hz, CH), 8.03 (d, 1H,
J = 8.4 Hz, CH), ppm; 13C-NMR: δ 114.50 (PhHC=C<),
128.02, 128.84, 127.90, 133.21 (C6H5), 128.49, 128.62,
127.88, 134.23 (C6H5), 130.34, 156.91, 169.15
(imidazolinone's carbons), 113.01, 136.00, 171.33 (thia-
zole's carbons) ppm; MS m/z (%): 332.10 (M+ + 1, 4%),
250.10 (26%), 189.04 (2%), 105.03 (100%), 77.18 (28%);

SOFAN ET AL.
11
Anal. calcd for C19H13N3OS (331): C, 68.86; H, 3.95; N,
12.68%; found: C, 68.81; H, 3.90; N, 12.63%.
4.10.5 | Ethyl 4-(4-benzylidene-5-oxo-
2-phenyl-4,5-dihydro-1H-imidazol-1-yl)
benzoate (15)
4.10.2 | 5-benzylidene-2-phenyl-3-(1H-
1,2,4-triazol-3-yl)-3,5-dihydro-4H-imidazol-
4-one (12)
White crystals; yield 80%; mp 145ꢀC; IR 1794, 1713
1
2(CO) cm−1; H-NMR δ 1.32 (t, 3H, J = 6.9 Hz, -CH3),
4.30 (q, 2H, J = 6.9 Hz, -CH-), 7.15(s, 1H, CH), 7.38-7.68
(m, 10H, Ar-H), 7.92 (d, 2H, J= 7.8 Hz, ArH), 8.03 (d, 2H,
J = 7.8 Hz, ArH) ppm; 13C-NMR: δ 14.12 (CH3), 60.03
(CH2), 114.50 (PhHC=C<), 128.02, 128.84, 127.90, 133.21
(C6H5), 128.49, 128.62, 127.88, 134.23 (C6H5), 130.34,
156.91, 169.15 (imidazolinone's carbons), 124.01, 125.02,
130.10, 141.20 (C6H4), 167.14 (CO) ppm; MS: m/z
396 (M+, 10%), 250.06 (22%), 165.07 (8%), 105.09 (100%),
77.07 (62%); Anal. calcd for C25H20N2O3: C, 75.74; H,
5.09; N, 7.07%; found: C, 78.69; H, 5.04; N, 7.03%.
Yellow crystals; yield 70%; mp 170ꢀC; IR 1793 (CO), 3159
(NH) cm−1; 1H-NMR: δ 7.33-7.67 (m, 11H, Ar-H), 7.84 (s,
1H, CH) ppm; 13C-NMR: δ 114.50 (PhHC=C<), 128.02,
128.84, 127.90, 133.21 (C6H5), 128.49, 128.62, 127.88,
134.23 (C6H5), 130.34, 156.91, 169.15 (imidazolinone's
carbons), 145.09, 148.02 (triazole's carbons) ppm; MS: m/
z (%): 315 (M+ + 5.11%), 258.14 (50%), 189.15 (28%),
105.10 (84%), 77.10 (52%); Anal. calcd for C18H13N5O: C,
68.56, H, 4.16, N, 22.21%; found: C, 68.51; H,
4.11; N, 22.16%.
4.11 | Synthesis of compound (16)
4.10.3 | 4-(4-benzylidene-5-oxo-2-phenyl-
4,5-dihydro-1H-imidazol-1-yl)-1,5-dimethyl-
2-phenyl-1,2-dihydro-3H-pyrazol-3-one (13)
In a round bottom flask (50 mL), reflux the solution of
compound 15 (3.96 g, 0.01 mol), thiosemicarbazide
(0.91 g, 0.01 mol) and 1 mL of conc. sulphuric acid in
20 mL of absolute ethanol for 4 h. Maintain the flask of
the reaction in refrigerator for overnight. Collect the
white precipitate by filtration, dry in air and recrystallize
from ethanol to afford compound 16.
Yellow crystals; yield 80%; mp 187ꢀC; IR 1719, 1640
2(CO), 3061(NH) cm−1; 1H-NMR: δ 8.36 (s, 1H, CH), 2.21
(s ,3H, -CH3),2.51 (s,3H, -CH3), 7.28-7.58 (m, 15H, Ar-H)
ppm; 13C-NMR: δ 14.51 (CH3), 35.03 (CH3), 114.50
(PhHC=C<), 128.02, 128.84, 127.90, 133.21 (C6H5),
128.49, 128.62, 127.88, 134.23 (C6H5), 130.34, 156.91,
169.15 (imidazolinone's carbons), 103.01, 134.00, 162.11
(pyrazolinone's carbons) ppm; MS: m/z 434 (M+, 3%),
417.36 (5%), 247.99 (58%), 178.22 (6%), 104,08 (100%),
77.02 (96%); Anal. calcd for C27H22N4O2: C, 74.64; H,
5.10; N, 12.89%; found: C, 74.60; H, 5.06; N, 12.85%.
4.11.1 | 2-(4-(4-benzylidene-5-oxo-
2-phenyl-4,5-dihydro-1H-imidazol-1-yl)
benzoyl) hydrazine-1-carbothioamide (16)
White crystals; yield 75%; mp 182ꢀC; IR 1713, 1669
(2CO), 3407 (NH2), 3121 (NH), 3254 (NH) cm−1 1H-
;
NMR: δ 7.15 (s, 1H, CH), 7.33-7.66 (m, 10H, Ar-H),
7.86-8.03 (m, 5H, Ar-H+ NH), 9.31 (d, 1H, NH), 10.51 (s,
2H, NH2) ppm; 13C-NMR: δ 14.12 (CH3), 60.03 (CH2),
114.50 (PhHC=C<), 128.02, 128.84, 127.90, 133.21
(C6H5), 128.49, 128.62, 127.88, 134.23 (C6H5), 130.34,
156.91, 169.15 (imidazolinone's carbons), 124.01, 125.02,
130.10, 141.20 (C6H4), 167.14 (CO) ppm; MS: m/z
441 (M+, 2%), 365.07 (16%), 251.05 (10%), 178.12 (28%),
104.01 (32%), 77.06 (28%), 44.01 (98%); Anal. calcd for
C24H19N5O2S: C, 65.29; H, 4.34; N, 15.86%; found: C,
65.24; H, 4.39; N, 15.90%.
4.10.4 | 3-(4-acetylphenyl)-5-benzylidene-
2-phenyl-3,5-dihydro-4H-imidazol-
4-one (14)
Pale yellow crystals; yield 85%; mp 158ꢀC; IR 1766, 1690
1
2(CO) cm−1; H-NMR: δ 7.85 (s, 1H, CH), 2.35 (s, 3H, -
CH3), 7.28-7.60 (m, 14H, Ar-H) ppm; 13C-NMR: δ 24.15
(CH3), 114.50 (PhHC=C<), 128.02, 128.84, 127.90, 133.21
(C6H5), 128.49, 128.62, 127.88, 134.23 (C6H5), 130.34,
156.91, 169.15 (imidazolinone's carbons), 123.01, 130.22,
136.91, 141.20 (C6H4), 192.94 (CO) ppm; MS: m/z
366 (M+, 1.09%), 249.14 (30%), 182.98 (70%), 104.06
(100%), 77.04 (95%); Anal. calcd for C24H18N2O2: C,
78.67; H, 4.95; N, 7.65%; found: C, 78.63; H,
5.09; N, 7.63%.
4.12 | Synthesis of compound (17)
Heat the solution of the derivative 15 (3.96 g, 0.01 mol)
and hydrazine hydrate (0.5 g, 0.01 mol) in 20 mL EtOH

12
SOFAN ET AL.
under reflux for 3 hours in a round bottom flask (50 mL).
The flask containing the reaction mixture was left to
stand for cooling at room temperature for 12 h. The solid
product that obtained by filtration, was recrystallized
from ethanol to produce the target compound.
(24%); Anal. calcd for C26H19N5O3: C, 69.48; H, 4.26; N,
15.58%; found: C, 69.43; H, 4.21; N, 15.63%.
ORCID
Mamdouh A. Sofan https://orcid.org/0000-0002-6666-
0218
Tarek M. Abou Elmaaty https://orcid.org/0000-0002-
4.12.1 | 4-(4-benzylidene-5-oxo-2-phenyl-
4,5-dihydro-1H-imidazol-1-yl)
benzohydrazide (17)
4877-0085
REFERENCES
[1] B. S. Vashi, D. S. Mehta, V. H. Shah, Indian J. Chem. 1995,
34B(9), 802.
[2] R. G. Ronnie, G. M. Luke, Chem. Abstr. 1983, 98, 1664.
[3] B. G. Michal, F. R. John, Antifungal Chemother. Annu. Rep.
Med. Chem. 1984, 19, 127.
White crystals; yield 75%; mp 190ꢀC; IR 1711, 1648
1
(2CO), 3318 (NH2), 3058 (NH) cm−1; H-NMR: δ 5.87 (s,
1H, CH), 6.54,657 (dd, 2H, J= 8.7 Hz, J= 8.7 Hz, NH2),
7.36-7.64 (m, 10H, Ar-H), 7.64 (d, 2H, J = 7.8 Hz, ArH),
7.87 (d, 2H, J = 7.4 Hz, ArH), 9.87 (br.,1H, NH) ppm;
13C-NMR: δ 114.50 (PhHC=C<), 128.02, 128.84, 127.90,
133.21 (C6H5), 128.49, 128.62, 127.88, 134.23 (C6H5),
130.34, 156.91, 169.15 (imidazolinone's carbons), 124.01,
125.02, 130.10, 141.20 (C6H4), 167.14 (CO) ppm; MS: m/z
382 (M+, 10%), 264.15 (34%), 251.13 (28%), 180.08 (14%),
107.53 (62%), 88.53 (100%); Anal. calcd for
C23H18N4O2: C, 77.24; H, 4.74; N, 14.65%; found: C,
77.20; H, 4.79; N, 15.60%.
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4.13 | Synthesis of compound 18
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Heat the round bottom flask (15 mL) containing a reac-
tion mixture of ethyl cyanoacetate (1.13 g, 0.01 mol) and
the benzohydrazide 17 (3.82 g, 0.01 mol) in 20 mL abso-
lute ethanol for 6 hours under reflux. Keep the reaction's
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room temperature (one day). The product 18 could be
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(2-cyanoacetyl)benzohydrazide (18)
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&
Yellow crystals; yield 70%; mp 220ꢀC; IR 1710, 1649
(2CO), 3111 (NH2), 3061 (NH), 2220 (CN) cm−1 1H-
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;
NMR: δ 3.98 (s, 2H, -CH2), 7.30-7.87(m, 14H, Ar-H), 8.80
(s, 1H, CH), 9.55 (s,1H, NH), 10.18 (s, 1H, NH) ppm; 13C-
NMR: δ 24.04 (CH2), 114.50 (PhHC=C<), 125.91 (CN),
128.02, 128.84, 127.90, 133.21 (C6H5), 128.49, 128.62,
127.88, 134.23 (C6H5), 130.34, 156.91, 169.15
(imidazolinone's carbons), 122.01, 123.02, 127.01, 141.20
(C6H4), 165.15 (CO), 169.99 (CO) ppm; MS: m/z 449 (M+,
4%), 383.37 (6%), 273.13 (86%), 248.14 (90%), 141.08

SOFAN ET AL.
13
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How to cite this article: Sofan MA, Abou
Elmaaty TM, Elkafafy A-KM, Abdel Mageed AEM.
Synthesis of novel 5-substituted imidazolinones as
insecticides against cotton leaf worm (Spodoptera
littoralis). J Heterocyclic Chem. 2019;1–13. https://
doi.org/10.1002/jhet.3788
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