Synthesis, characterization, and biological studies of chalcone derivatives containing Schiff bases: Synthetic derivatives for the treatment of epilepsy and Alzheimer's disease

Article abstract of DOI:10.1002/ardp.202000202

In this study, first, Schiff base-containing chalcone derivatives were synthesized. The human carbonic anhydrase (hCA) isoenzymes I and II were then purified from human erythrocytes using Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. In a

Full text of DOI:10.1002/ardp.202000202

Received: 17 June 2020
Revised: 23 July 2020
Accepted: 29 July 2020
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DOI: 10.1002/ardp.202000202
F U L L P A P E R
Synthesis, characterization, and biological studies of chalcone
derivatives containing Schiff bases: Synthetic derivatives for
the treatment of epilepsy and Alzheimer's disease
Ümit M. Koçyiğit1
| Hayreddin Gezegen2
| Parham Taslimi3
1Department of Basic Pharmaceutical Sciences,
Division of Biochemistry, Faculty of Pharmacy,
Sivas Cumhuriyet University, Sivas, Turkey
Abstract
In this study, first, Schiff base‐containing chalcone derivatives were synthesized. The
human carbonic anhydrase (hCA) isoenzymes I and II were then purified from human
erythrocytes using Sepharose‐4B‐L‐tyrosine‐sulfanilamide affinity chromatography.
In addition, the inhibitory effects of the newly synthesized compounds on the
activities of hCA and acetylcholinesterase (AChE) were investigated in vitro, using
the esterase and acetylcholine iodide method. The IC50 values were determined and
the Ki values of AChE and hCA activities were calculated from the Lineweaver–Burk
graphs determined in this study. The hCA I isoform was inhibited by these chalcone
derivatives containing Schiff bases (3a–j and 5a–f) in low nanomolar levels, whose
Ki values ranged between 141.88 24.10 and 2,234.47 38.11 nM. Against
the physiologically dominant isoform hCA II, the compounds demonstrated Ki
values varying from 199.31 40.45 to 602.79 263.22 nM. Also, these compounds
effectively inhibited AChE, with Ki values ranging from 20.41 6.04 to
125.94 23.88 nM. According to these results, the newly synthesized molecules
were found to be potent inhibitors of these enzymes.
2Department of Nutrition and Dietetics,
Faculty of Health Sciences, Sivas Cumhuriyet
University, Sivas, Turkey
3Department of Biotechnology, Faculty of
Science, Bartin University, Bartin, Turkey
Correspondence
Ümit M. Koçyiğit, Department of Basic
Pharmaceutical Sciences, Division of
Biochemistry, Faculty of Pharmacy,
Cumhuriyet University, 58140 Sivas, Turkey.
Email: ukocyigit@cumhuriyet.edu.tr
Funding information
Scientific Research Project Fund of Sivas
Cumhuriyet University, Grant/Award Number:
SHMYO‐013
K E Y W O R D S
acetylcholinesterase, carbonic anhydrase, chalcones, enzyme inhibition, Schiff base
respect, chalcones are ideal compounds for forming carbon–carbon,[11]
carbon–sulfur,[12] and carbon–nitrogen bonds. Chalcones are chemically
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1
INTRODUCTION
Chalcones are members of the flavonoid family that can be obtained
both naturally and synthetically, and they have a wide spectrum of
biological activity.[1] Therefore, in recent years, chalcone and its deri-
vatives have received increasing attention, and many studies have been
particularly performed on biological activity (Figure 1). Chalcones and
chalcone analogs are valuable intermediates in organic synthesis and
they have a wide spectrum of biological activity.[2,3]
highly active compounds, as they contain both a substituted aromatic ring
and an α,β‐unsaturated carbonyl unit.[13–16]
Schiff bases were first obtained in 1860 by the German chemist
Hugo Schiff. Very weak carbonyl compounds give condensation
reactions with primary amine groups, resulting in a carbon–nitrogen
double bond.[17] This link is called the link of the imine. If the carbonyl
compound is an aldehyde, the bond formed is called aldimine, and
when it is a ketone, the bond formed is called the ketimine. Schiff
bases are an important class of ligands and have had a very large field
of study in coordination chemistry to date. Schiff base derivatives are
important compounds used in biological, pharmacological and ana-
lytical studies as well as in industrial applications. For example, some
Schiff bases act as corrosion inhibitors in steel and dyestuff.[18–20]
Studies carried out on chalcones revealed that they showed anti-
bacterial,[4] antimalarial,[5] antihelminitic, amoebicidal, antiulcer, antiviral,
insecticidal,[6] antiprotozoal, anticancer,[7] anti‐inflammatory,[8] and cyto-
toxic anti‐HIV[9] activities. In addition, the α,β‐unsaturated parts in the
structures of chalcones make them chemically important and are used as
the starting agent in the synthesis of heterocyclic compounds.[10] In this
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Arch Pharm. 2020;e2000202.
wileyonlinelibrary.com/journal/ardp
© 2020 Deutsche Pharmazeutische Gesellschaft
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also be associated with AChE‐inhibiting drugs. Examples of these in-
hibiting drugs are inhibitors such as dichlorovinyl dimethyl phosphate,
tetrahydroaminoacridine, galantamine, and rivastigmine.[31–33]
In this study, we first synthesized 12 new and four known (3e,[34]
5b,[35] 5d,[36] and 5e[37]) chalcone derivatives containing Schiff bases,
which were considered to have a broad biological activity, and per-
formed the characterization of these compounds. To determine the
antiepileptic and anticholinergic properties of the synthesized com-
pounds, their inhibitory potentials against carbonic anhydrase I–II
isoenzymes and AChE enzymes were investigated in this study.
FIGURE 1 Chalcone (i) and Schiff base (ii)
Carbonic anhydrase (CA; carbonate hydrolysis, EC: 4.2.1.1) is a
metalloenzyme that contains zinc (Zn2+) ions in its active area and is
very important for biological systems.[21,22] Carbonic hydrase is
essentially a very important enzyme that plays a role in many phy-
siological events such as ensuring the dissolution, transport, and
removal of CO2 formed during breathing, as well as acid–base bal-
ance, ion exchange, and regulation of the cardiovascular system. The
enzyme, first isolated from human erythrocytes, has been studied in
many living organisms and tissues.[23,24]
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2
RESULTS AND DISCUSSION
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2.1
Chemistry
Recently, it was shown that chalcone derivatives are effective anti-
microbial and antioxidant additives to self‐dispersed oils.[22,23] In this
article, we report the synthesis of chalcone derivatives containing
Schiff bases 3a–j and 5a–f, and their biological activity against car-
bonic anhydrase I–II isoenzymes and AChE enzymes.
Acetyl CoA is a metabolic product of pyruvate in glycolysis.
Alzheimer's disease (AD) occurs as a result of decreased neuro-
transmitters in the brain. A maximum decrease of neurotransmitters
occurs in the case of dementia and neurodegenerative disease. AD was
found to be a dysfunction of memory. The decrease in the level of
acetylcholine (ACh) in the brain is the biggest biochemical factor of
this disease.[25,26] There is no cure for this disease. Currently, the
treatments applied are aimed at eliminating the symptoms of this
disease. There is no treatment method that eliminates it. Acet-
ylcholinesterase (AChE; EC 3.1.1.7) is a nonspecific enzyme that hy-
drolyzes lipotropic acetylcholine in tissues that are free or in
combination with phospholipids. AChE inhibitors, such as rivastigmine
and donepezil, are generally used for this purpose.[27,28] Recent studies
have found that the amount of butyrylcholinesterase (BChE) in the
brain of Alzheimer's patients is higher than in normal brains.[29,30]
Therefore, it is estimated that butyrylcholinesterase inhibition may
The synthesis of chalcone derivatives containing Schiff bases was
carried out in one step by treating 3′‐aminoacetophenone (1) and 4′‐
aminoacetophenone (4) with aromatic aldehydes (2a–j) in 1:2 ratios
(Scheme 1). In the reaction,
1 equivalent of aromatic aldehyde
reacted with the acetyl part of aminoacetophenone via the
Claisen–Schmidt condensation in basic media and the chalcone skeleton
was formed. Besides, the remaining aldehyde reacted with the amine
group in the acetophenone and formed the Schiff base (aldimine
structure). As a result of the studies, it was observed that 3′‐
aminoacetophenone (1) completely reacted with all the aldehydes used
and gave the expected product (3a–j; Table 1). But in the reaction of
4′‐aminoacetophenone (4) with 4‐(methylthio)benzaldehyde (2g), it was
observed that the chalcone derivative (I), and not the expected product
SCHEME 1 The reaction scheme for the synthesis of chalcone derivatives containing Schiff bases

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TABLE 1 Synthesized chalcone derivatives containing Schiff bases
Entry
Compounds
Yields (%)
1
82
3a
3b
3c
2
81
3
4
78
84
3d
5
6
7
77
84
70
3e
3f
3g
3h
8
9
75
80
3i
3j
10
11
79
82
5a
(Continues)

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TABLE 1 (Continued)
Entry
Compounds
Yields (%)
12
81
13
80
14
15
16
17
78
79
83
5f
Could not be
synthe-
sized
5g
Could not be
obtained
pure
18
19
5h
5i
Could not be
obtained
pure
20
Could not be
obtained
pure

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SCHEME 2 The reaction scheme for 5h–j
(5g), was formed. In the reactions given by 4′‐aminoacetophenone (4)
with 4‐(trifluoromethyl)benzaldehyde (2h), 4‐nitrobenzaldehyde (2i),
and thiophene‐2‐carbaldehyde (2j), the product obtained was a mixture
of 4′‐aminochalcone derivative (I) and chalcone derivative containing
Schiff bases (5h–j; Scheme 2; Table 1). When the reaction time was
increased to 24 hr, there was no change in the product composition. The
reaction mixture was subjected to column chromatography on silica gel,
eluting with AcOEt/hexane (2:8) in order to separate the Schiff base in
the medium, but the imine structure was observed to undergo hydro-
lysis. Targeted compounds (5h–j) could not be obtained purely, as
the base strength of 4′‐aminoacetophenone (4) was less than that of
3′‐aminoacetophenone (1).
1.2 Hz, 1H), 7.47–7.31 (m, 5H), 7.19 (tdd, J = 8.3, 2.7, 1.0 Hz, 1H), and
7.13–7.06 (m, 1H) ppm, respectively, thus confirming this structure
(Figure 2). When the 13C‐NMR spectrum of 3a is analyzed, it is clearly
seen that the carbons and coupling constants interact with the fluorine in
the structure. Whereas the carbonyl carbon (C7) in the structure re-
sonates at 189.8 ppm, the ipso carbon atoms, to which the fluorides are
attached (C14 and C21), are resonated by
a doublet at 163.2
(J = 247.2 Hz) and 163.1 (J = 246.9 Hz) ppm, respectively. The carbon
atoms of the imine and alkene unit (C16 and C9) interacted with fluorine
through the four bonds and gave a doublet at 160.1 (J = 3.2 Hz) and
143.7 (J = 3.0 Hz) ppm. Other carbon atoms (C11 and C18), which are
split into a doublet due to the interactions with fluorine through four
bonds, gave a signal at 125.4 (J = 3.0 Hz) and 124.7 (J = 3.0 Hz) ppm. Of
the carbons that interact with fluorine through three bonds, ipso carbons
(C10 and C17) gave a doublet at 138.2 (J = 7.4 Hz) and 137.1 (J = 7.7
Hz) ppm, and also others (C19 and C12) gave a doublet at 130.6
(J = 8.3 Hz) and 130.5 (J = 8.0 Hz) ppm. In addition, the carbon atoms in-
teracting with the fluorines through two bonds (C20, C13, C22, and C15)
were split into a doublet, as expected, giving signals at 118.8 (J = 21.7 Hz),
117.6 (J = 21.4 Hz), 114.9 (J = 22.4 Hz), and 114.6 (J = 21.5 Hz) ppm, re-
spectively. The remaining signals in the 13C‐NMR spectrum are also in
harmony with the structure.
The structures of synthesized compounds (3a–j and 5a–f;
Table 1) were determined by spectroscopic studies (1H‐NMR [nuclear
magnetic resonance], 13C‐NMR, Fourier transform infrared [FTIR], and
quadrupole time‐of‐flight [Q‐TOF] liquid chromatography‐mass spectro-
metry [LC/MS]). In the FTIR spectrum of 3a, stretching vibrations of C═O
and C═N groups were observed at 1,662 and 1,625 cm−1, respectively. In
the 1H‐NMR spectrum of 3a, the H‐atom of the aldimine group (H–C16)
gave a doublet at 8.47 ppm (J = 1.3 Hz). From the aromatic H‐atoms,
H–C4 gave a doublet of doublets at 7.89 ppm (J = 7.7, 1.7, 1.2 Hz),
whereas the H–C6 gave a multiplet at 7.84–7.80 ppm. Aliphatic protons
in the structure are resonated by giving the AB system. However, only
one side of the system is observed (H–C9) as a doublet at 7.77 ppm in the
spectrum (J = 15.7 Hz). The signals of the H–C8 atom, which forms the
other side of the AB system, overlapped with the signals of the H–C3
atom and gave a multiplet at 7.56–7.49 ppm. Signals of other aromatic
H‐atoms appear at 7.67 (ddd, J = 9.4, 2.6, 1.5 Hz, 1H), 7.64 (dt, J = 7.7,
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2.2
Biochemical studies
The inhibitors of some CA isoenzymes (like CA I and CA II) are utilized to
design novel classes of drugs for glaucoma and epilepsy. Additionally,
novel CA inhibitors have been required to expand as therapeutic factors.
Various groups have studied the inhibition of hCAs with catecholamines,
thiourea derivatives, bromophenols, anions, uracil derivatives, and sulfo-
namides. In addition, chalcones and pyrazoles have also been studied to
inhibit hCAs as well.[22,23] The results presented in Table 2 reveal that
chalcone derivatives containing Schiff bases had an effective inhibition
against hCA I isoform. The hCA I isoform was inhibited by 3a–j and 5a–f
in nanomolar levels, whose Ki value ranged between 141.88 24.10 and
FIGURE 2 Numbering carbon atoms of 3a

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TABLE 2 Inhibition results of 3a–j and 5a–f against carbonic anhydrase isoenzymes (I/II) and acetylcholinesterase enzymes
IC50 (nM)
hCA I
Ki (nM)
Compounds
r2
hCA II
401.37
r2
AChE
107.66
97.13
141.14
115.14
79.22
81.00
117.18
95.16
91.31
128.55
150.98
111.23
72.77
67.33
92.50
131.77
–
r2
hCA I
hCA II
279.22 64.12
AChE
3a
395.13
354.11
327.99
456.98
388.37
311.97
429.25
425.73
370.22
369.57
342.40
340.15
331.88
307.93
226.10
366.27
1,023.10
–
0.9820
0.9760
0.9799
0.9819
0.9500
0.9790
0.9740
0.9813
0.9934
0.9723
0.9913
0.9969
0.9776
0.9804
0.9947
0.9812
0.9758
–
0.9740
0.9677
0.9649
0.9673
0.9783
0.9930
0.9637
0.9427
0.9528
0.9756
0.9598
0.9894
0.9812
0.9635
0.9691
0.9943
0.9630
–
0.9726
0.9924
0.9432
0.9660
0.9661
0.9692
0.9808
0.9700
0.9804
0.9812
0.9884
0.9774
0.9759
0.9880
0.9784
0.9932
–
355.23 76.25
2,234.47 38.11
312.44 37.13
381.14 21.22
324.46 81.25
325.14 146.10
306.13 23.13
288.47 36.85
281.76 38.13
281.46 79.03
358.03 49.75
368.21 67.83
352.11 78.05
256.24 11.21
141.88 24.10
384.94 94.06
52.93 10.25
82.27 34.02
82.77 14.18
50.11 22.46
24.03 11.01
28.07 12.33
87.11 39.01
3b
295.28
401.37
471.87
369.24
368.22
459.02
445.37
449.21
387.08
437.50
341.01
452.07
358.84
340.13
303.94
1,168.22
–
199.31 40.45
443.21 199.21
450.27 197.46
602.79 263.22
359.84 148.30
569.44 249.14
3c
3d
3e
3f
3g
3h
479.52 176.22 46. 70 12.52
3i
398.35 81.32
302.44 81.25
61.93 19.72
110.26 5.57
3j
5a
459.66 104.77 125.94 23.88
5b
337.31 91.55
494.40 124.28
421.05 184.18
363.50 143.27
350.03 54.82
97.20 30.71
20.41 6.04
5c
5d
37.40 176.01
30.90 12.11
98.04 30.71
5e
5f
AZAa
Tacrinea
859.07 219.25 1,022.20 279.30
–
436.01
0.9924
–
–
231.55 32.30
aAcetazolamide (AZA) was used as a standard inhibitor for all human carbonic anhydrase (hCA) I and II and tacrine (TAC) was used as a standard inhibitor
for acetylcholinesterase (AChE) enzyme.
2,234.47 38.11 nM. Indeed, acetazolamide (AZA), as a broad‐specificity
CA inhibitor, showed a Ki value of 859.07 219.25 nM against hCA I.
Among the inhibitor compounds, the 5e and 5d were obtained to be as
hyperstimulation of muscarinic and nicotinic receptors. Reversible
AChE inhibitors are extensively utilized for the treatment of
neurodegenerative diseases, whereas irreversible inhibitor com-
pounds are associated with toxic effects. Indeed, irreversible AChE
inhibitors (AChEIs) include chemical warfare factors and many
organophosphorus molecules used as insecticides and pesticides.
All chalcone derivatives containing Schiff bases (3a–j and 5a–f)
exhibited a significantly higher AChE inhibitory activity than ta-
crine as control molecule. Furthermore, the Ki values of chalcone
derivatives containing Schiff bases (3a–j and 5a–f) and tacrine are
summarized in Table 2. As can be observed from the results re-
corded in Table 2 and Figure 3, compounds 3a–j and 5a–f effec-
tively inhibited AChE, with Ki values ranging from 20.41 6.04 to
125.94 23.88 nM. Thus, all of these compounds had almost si-
milar inhibition profiles. The most active compounds, 5h and 3d,
showed Ki values of 20.41 6.04 and 24.03 11.01 nM. For AChE,
IC50 values of TAC and some chalcone derivatives containing
Schiff bases (3a–j and 5a–f) exhibit the following order: 5d
(67.33 nM, r2: .9880) < 5c (72.77 nM, r2: .9759) < 3e (79.22 nM, r2:
.9661) < 3f (81.00 nM, r2: .9692) < TAC (436.01 nM, r2: .9924).
AChEIs like donepezil are approved by the United States Food and
Drug Administration for the treatment of AD, and they are sup-
ported by clinical trial data to be utilized in the treatment of
Parkinson's disease and vascular dementia.
excellent hCA
I inhibitors with Ki values of 141.88 24.10 and
256.24 11.21 nM, respectively. The hCA I inhibition effects of chalcone
derivatives containing Schiff bases (3a–j and 5a–f) were found to be
greater than AZA. For hCA I, half‐maximal inhibitor concentrations (IC50
)
values of AZA as a positive control and some chalcone derivatives con-
taining Schiff bases (3a–j and 5a–f) exhibit the following order: 5e
(226.10 nM, r2: .9947) < 5d (307.93 nM, r2: .9804) < 3f (311.97 nM, r2:
.9790) < 3c (327.99 nM, r2: .9799) < AZA (1,023.10 nM, r2: .9758). Against
the hCA II isoform, the chalcone derivatives containing Schiff bases (3a–j
and 5a–f) demonstrated Ki values varying from 199.31 40.45 to
602.79 2,633.22 nM (Table 2). These chalcones containing Schiff bases
(3a–j and 5a–f) were observed to have high inhibition effects against hCA
II. Additionally, AZA showed a Ki value of 1,022.20 279.30 nM against
hCA II. 3b and 3a had shown the maximum inhibition effect, with Ki
values of 199.31 40.45 and 279.22 64.12 nM, respectively. For hCA II,
IC50 values of AZA and some synthesized compounds (3a–j and 5a–f)
exhibit the following order: 3b (295.28 nM, r2: .9677) < 5f (303.94 nM, r2:
.9943) < 5e (340.13 nM, r2: .9691) < 5b (341.01 nM, r2: .9894) < AZA
(1,168.22 nM, r2: .9630).
The enzyme can be inactivated by various inhibitors, leading to
ACh accumulation and also disrupted neurotransmission caused by

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(KiTAC/Ki5c = 11.34) against AChE. The findings could be useful in de-
veloping and synthesizing new metabolic enzyme inhibitors as possible
candidates for the design of new drugs for the future treatment of
certain diseases including epilepsy and Alzheimer's disease.
hCA I
231
198
165
132
99
66
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4
EXPERIMENTAL
33
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4.1
Chemistry
0
-6
2
10
18
26
34
42
1/[S] (nM)-1
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4.1.1
General
hCA II
Anhydrous sodium sulfate was used as a drying agent for the organic
phase. Column chromatography was performed on silica gel (SiO2,
60–230 mesh; Merck). Melting points were measured on an Electro-
thermal 9100 apparatus. IR spectra (KBr disc) were recorded on a
Jasco FT/IR‐430 spectrometer. 1H‐NMR and 13C‐NMR spectra were
recorded on a JEOL (400 MHz) JNM‐ECZ400S/L1 NMR instrument in
CDCl3 and (d6) dimethyl sulfoxide (DMSO); δ in ppm relative to Me4Si
(δ: 0.00) for 1H‐NMR; CDCl3 (δ: 77.0), and (d6)DMSO (δ: 39.5) for
13C‐NMR spectra as internal standards; J in Hz. Agilent Technology
Inc. of 1260 Infinity HPLC System was coupled with 6530 Q‐TOF
LC/MS detector and ZORBAX SB‐C18 (2.1 × 50 mm, 1.8 μm) column.
The original spectra of the investigated compounds are provided
as Supporting Information, together with their InChI codes and some
biological activity data.
231
198
165
132
99
66
33
0
-6
2
10
18
26
34
42
1/[S] (nM)-1
AChE
110
100
90
80
70
60
50
40
30
20
10
0
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4.1.2
General procedure the synthesis of Schiff
base‐containing chalcone derivatives
2.5 M NaOH (5 ml) was added to a solution of 3′‐aminoacetophenone (1)
or 4′‐aminoacetophenone (4) (7.5 mmol) in EtOH (50 ml). The corre-
sponding benzaldehyde derivative, which was then weighed in a separate
container and dissolved in 30 ml of EtOH, was added to this mixture. The
corresponding aromatic aldehyde (2a–j) (15 mmol), which was then
weighed in a beaker and dissolved in 30 ml of EtOH, was added onto the
mixture. An additional 20 ml of EtOH was added to the mixture and
stirred at room temperature for 4 hr. At the end of the reaction, the
mixture, which was precipitated, was transferred to a beaker containing
250 ml of water and stirred for a while. It was then dried by vacuum
filtration. The obtained products (3a–j and 5a–f) were purified by crys-
tallization from EtOH.
-8
-6
-4
-2
0
2
4
6
8
10 12
1/[S] (nM)-1
FIGURE 3 Determination of Lineweaver–Burk graphs for
excellent inhibitors of human carbonic anhydrase (hCA)‐I, hCA‐II,
and acetylcholinesterase (AChE) enzymes
|
3
CONCLUSIONS
In conclusion, in this study, a series of chalcone derivatives con-
taining Schiff bases (3a–j and 5a–f) was synthesized in high yields
(70–84%) and investigated in vitro for their inhibition properties
against AChE and the hCA I and II isoforms. Synthesized compounds
demonstrated remarkable inhibition activities as compared with
standard drugs (Table 2). In addition, compound 5e with p‐OCH3
substituent showed the best inhibition activity (KiAZA/Ki5e = 6.05)
against hCA I, compound 3b with m‐Cl substituent showed the best
inhibition activity (KiAZA/Ki3b = 5.14) against hCA II, and compound
5c with m‐Br substituent showed the best inhibition activity
(2E)‐3‐(3‐Fluorophenyl)‐1‐(3‐{[(1E)‐(3‐fluorophenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (3a)
Yellow solid. Yield: 82%, m.p.: 136–138°C. IR (KBr, cm−1): 3,066,
3,042, 2,911, 1,662, 1,625, 1,605, 1,581, 1,483, 1,447, 1,366, 1,326,
1,261, 1,239, 1,189, 1,162, 1,144, 1,046, 974, 903, 850, 771, 684,
672, 518, and 445. 1H‐NMR (400 MHz, CDCl3) δ 8.47 (d, J = 1.3 Hz,
1H), 7.89 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.84–7.80 (m, 1H), 7.77
(d, J = 15.7 Hz, 1H), 7.67 (ddd, J = 9.4, 2.6, 1.5 Hz, 1H), 7.64 (dt, J = 7.7,
1.2 Hz, 1H), 7.56–7.49 (m, 2H), 7.47–7.31 (m, 5H), 7.19 (tdd, J = 8.3,

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2.7, 1.0 Hz, 1H), and 7.13–7.06 (m, 1H). 13C‐NMR (101 MHz, CDCl3) δ
189.8, 163.2 (d, J = 247.2 Hz), 163.1 (d, J = 246.9 Hz), 160.1
(d, J = 3.2 Hz), 152.1, 143.7 (d, J = 3.0 Hz), 139.1, 138.2 (d, J = 7.4 Hz),
137.1 (d, J = 7.7 Hz), 130.6 (d, J = 8.3 Hz), 130.5 (d, J = 8.0 Hz), 129.7,
126.4, 125.8, 125.4 (d, J = 3.0 Hz), 124.7 (d, J = 3.0 Hz), 123.1, 120.7,
118.8 (d, J = 21.7 Hz), 117.6 (d, J = 21.4 Hz), 114.9 (d, J = 22.4 Hz),
and 114.6 (d, J = 21.5 Hz). Q‐TOF LC/MS: 348.1339 ([M+H]+,
C22H15F2NO+; calc. 348.1194).
(2E)‐3‐(4‐Methoxyphenyl)‐1‐(3‐{[(1E)‐(4‐methoxyphenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (3e)[34]
Yellow solid. Yield: 77% (Lit: 76%),[34] m.p.: 123–126°C (Lit: 132°C).[34]
IR (KBr, cm−1): 3,019, 2,964, 2,901, 2,839, 1,651, 1,627, 1,577, 1,509,
1,490, 1,453, 1,418, 1,320, 1,301, 1256, 1184, 1,167, 1,105, 1,021,
989, 875, 824, 787, 678, 528, and 512. 1H‐NMR (400 MHz, CDCl3)
δ 8.47 (s, 1H), 7.92–7.80 (m, 5H), 7.63 (d, J = 8.7 Hz, 2H), 7.53
(t, J = 7.7 Hz, 1H), 7.47 (d, J = 15.6 Hz, 1H), 7.42 (d, J = 7.9 Hz, 1H), 7.02
(d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 3.90 (s, 3H), and 3.87 (s, 3H).
13C‐NMR (101 MHz, CDCl3) δ 190.2, 162.5, 161.7, 160.6, 152.7, 144.8,
139.6, 130.7 (2C), 130.3 (2C), 129.3, 129.1, 127.6, 125.5, 125.3, 120.5,
119.8, 114.4 (2C), 114.3 (2C), 55.5, and 55.4. Q‐TOF LC/MS: 254.1274
([M+H]+, [C24H21NO3+–C8H8O2]; calc. 372.159) The expected mass
could not be observed due to the hydrolysis of the imine structure in
the HPLC column.
(2E)‐3‐(3‐Chlorophenyl)‐1‐(3‐{[(1E)‐(3‐chlorophenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (3b)
Yellow solid. Yield: 81%, m.p.: 116–119°C. IR (KBr, cm−1): 3,064,
2,980, 2,921, 2,865, 1,662, 1,625, 1,596, 1,569, 1,471, 1,433, 1,364,
1,320, 1,268, 1,211, 1,186, 1,153, 1,077, 1,047, 985, 977, 895, 776,
684, and 565. 1H‐NMR (400 MHz, CDCl3) δ 8.46 (s, 1H), 7.95
(t, J = 1.8 Hz, 1H), 7.92–7.86 (m, 1H), 7.82 (t, J = 1.8 Hz, 1H),
7.78–7.72 (m, 2H), 7.63 (t, J = 1.7 Hz, 1H), 7.57–7.53 (m, 1H),
7.52–7.46 (m, 2H), 7.46–7.38 (m, 3H), and 7.37–7.30 (m, 2H).
13C‐NMR (101 MHz, CDCl3) δ 189.7, 159.9, 152.0, 143.5, 139.1,
137.7, 136.7, 135.2, 135.1, 131.8, 130.6, 130.3, 130.2, 129.7, 128.5,
128.0, 127.5, 126.9, 126.4, 125.8, 123.1, and 120.7. Q‐TOF LC/MS:
381.3118 ([M+H]+, C22H15Cl2NO+; calc. 380.0604).
(2E)‐3‐(3‐Thienyl)‐1‐(3‐{[(1E)‐3‐thienylmethylene]amino}phenyl)‐
prop‐2‐en‐1‐one (3f)
Yellow solid. Yield: 84%, m.p.: 106–109°C. IR (KBr, cm−1): 3,085,
2,967, 2,882, 1,651, 1,615, 1,578, 1,567, 1,517, 1,436, 1,404, 1,322,
1,283, 1,231, 1,167, 1,141, 1,046, 978, 913, 862, 773, 682, 645, 606,
and 582. 1H‐NMR (400 MHz, CDCl3) δ 8.46 (s, 1H), 7.86–7.76
(m, 4H), 7.67 (d, J = 5.1 Hz, 1H), 7.59–7.54 (m, 1H), 7.46 (td, J = 7.7,
1.5 Hz, 1H), and 7.41–7.31 (m, 5H). 13C‐NMR (101 MHz, CDCl3) δ
190.4, 155.5, 152.5, 140.6, 139.3, 138.5, 138.2, 131.2, 129.6, 129.5,
127.2, 127.0, 126.0, 125.9, 125.5, 125.4, 121.7, and 120.6. Q‐TOF
LC/MS: 324.066 ([M+H]+, C18H13NOS2+; calc. 324.051).
(2E)‐3‐(3‐Bromophenyl)‐1‐(3‐{[(1E)‐(3‐bromophenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (3c)
Yellow solid. Yield: 78%, m.p.: 115–118°C. IR (KBr, cm−1): 3,062,
3,929, 3,884, 1,661, 1,626, 1,591, 1,569, 1,470, 1,440, 1,429, 1,311,
1,241, 1,208, 1,183, 1,151, 1,089, 1,042, 986, 879, 780, 773, 683,
675, and 575. 1H‐NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 8.12
(t, J = 1.7 Hz, 1H), 7.92–7.87 (m, 1H), 7.83–7.77 (m, 3H), 7.74
(d, J = 15.7 Hz, 1H), 7.62 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H), 7.56–7.50
(m, 4H), 7.43 (ddd, J = 7.9, 2.1, 1.1 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), and
7.29 (t, J = 7.8 Hz, 1H). 13C‐NMR (101 MHz, CDCl3) δ 189.7, 159.8,
152.0, 143.4, 139.1, 137.9, 137.0, 134.7, 133.5, 131.5, 130.9, 130.6,
130.4, 129.7, 127.9, 127.4, 126.4, 125.8, 123.3, 123.2, 123.1, and
120.7. Q‐TOF LC/MS: 468.4174 ([M+H]+, C22H15Br2NO+; calc.
467.9593).
(2E)‐3‐[4‐(Methylthio)phenyl]‐1‐[3‐({(1E)‐[4‐(methylthio)phenyl]‐
methylene}amino)phenyl]prop‐2‐en‐1‐one (3g)
Yellow solid. Yield: 70%, m.p.: 114–116°C. IR (KBr, cm−1): 3,164,
3,051, 2,980, 2,918, 2,863, 1,653, 1,619, 1,606, 1,576, 1,551, 1,491,
1,437, 1,404, 1,327, 1,300, 1,220, 1,187, 1,149, 1,090, 1,047, 1,012,
981, 919, 815, 788, 680, 510, and 493. 1H‐NMR (400 MHz, CDCl3) δ
8.48 (s, 1H), 7.89 (d, J = 7.7 Hz, 1H), 7.83 (t, J = 12.6 Hz, 4H), 7.59
(d, J = 8.4 Hz, 2H), 7.56–7.50 (m, 2H), 7.44 (d, J = 6.5 Hz, 1H), 7.34
(d, J = 8.3 Hz, 2H), 7.28 (dd, J = 5.4, 2.9 Hz, 2H), 2.56 (s, 3H), and 2.54
(s, 3H). 13C‐NMR (101 MHz, CDCl3) δ 190.1, 160.6, 152.5, 144.5,
143.8, 142.5, 139.4, 132.6, 131.4, 129.4, 129.3 (2C), 128.9 (2C),
126.0 (2C), 125.8, 125.7 (2C), 125.4, 120.9, 120.6, 15.2, and 15.1.
Q‐TOF LC/MS: 404.1334 ([M+H]+, C24H21NOS2+; calc. 404.1137).
(2E)‐3‐(4‐Fluorophenyl)‐1‐(3‐{[(1E)‐(4‐fluorophenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (3d)
Yellow solid. Yield: 84%, m.p.: 126–128°C. IR (KBr, cm−1): 3,063,
3,049, 3,004, 1,663, 1,626, 1,598, 1,584, 1,572, 1,506, 1,442, 1,411,
1,324, 1,313, 1,294, 1,241, 1,221, 1,151, 1,045, 975, 901, 823, 785,
676, and 500. 1H‐NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 7.91 (ddd,
J = 8.3, 5.2, 2.5 Hz, 2H), 7.87 (dt, J = 7.7, 1.3 Hz, 1H), 7.83–7.76
(m, 2H), 7.63 (ddd, J = 8.3, 5.2, 2.5 Hz, 2H), 7.55–7.44 (m, 2H),
7.41 (ddd, J = 7.8, 2.0, 0.9 Hz, 1H), 7.20–7.14 (m, 2H), and
7.13–7.06 (m, 2H). 13C‐NMR (101 MHz, CDCl3) δ 189.0, 164.9
(d, J = 252.9 Hz), 164.1 (d, J = 252.0 Hz), 159.5, 152.3, 143.6,
139.2, 132.2 (d, J = 2.9 Hz), 131.1, 131.0 (d, J = 8.9 Hz, 2 C), 130.4
(d, J = 8.5 Hz, 2 C), 129.5, 125.9, 125.5, 121.6 (d, J = 1.6 Hz), 120.5,
116.2 (d, J = 21.9 Hz, 2C), and 116.1 (d, J = 22.0 Hz, 2C). Q‐TOF
LC/MS: 348.1328 ([M+H]+, C22H15F2NO+; calc. 348.1194).
(2E)‐3‐[4‐(Trifluoromethyl)phenyl]‐1‐[3‐({(1E)‐[4‐(trifluoromethyl)‐
phenyl]methylene}amino)phenyl]prop‐2‐en‐1‐one (3h)
Yellow solid. Yield: 75%, m.p.: 103–105°C. IR (KBr, cm−1): 2,980,
2,972, 2,938, 2,865, 2,825, 1,663, 1,625, 1,607, 1,572, 1,455, 1,438,
1,413, 1,318, 1,287, 1,216, 1,166, 1,104, 1,059, 1,032, 1,014, 958,
918, 907, 829, 790, 687, 673, 591, and 499. 1H‐NMR (400 MHz,
CDCl3) δ 8.56 (s, 1H), 8.03 (d, J = 8.1 Hz, 2H), 7.92 (dt, J = 7.7, 1.4 Hz,
1H), 7.87–7.80 (m, 2H), 7.74 (d, J = 8.1 Hz, 4H), 7.66 (d, J = 8.3 Hz,
2H), 7.62 (d, J = 15.7 Hz, 1H), 7.56 (t, J = 7.8 Hz, 1H), and 7.47 (ddd,
J = 7.9, 2.1, 1.1 Hz, 1H). 13C‐NMR (101 MHz, CDCl3) δ 189.62,
159.92, 151.98, 143.20, 139.02, 138.99, 138.98, 138.94, 138.92,

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138.91, 138.22, 133.36, 133.03, 132.24, 131.92, 129.79, 129.23
(2C), 128.68 (2C), 126.62, 126.09, 126.04, 126.01, 125.97, 125.97,
125.94, 125.90, 125.89, 125.86, 125.25, 124.03, 122.54, and 120.76.
Q‐TOF LC/MS: 448.1362 ([M+H]+, C24H15F6NO+; calc. 448.1130).
(s, 1H), 8.30 (d, J = 8.6 Hz, 2H), 8.17–8.07 (m, 2H), 8.05–8.00 (m, 1H),
7.95 (dd, J = 6.4, 1.2 Hz, 1H), 7.86 (dt, J = 6.5, 1.6 Hz, 1H), 7.75
(d, J = 15.6 Hz, 1H), 7.66 (ddd, J = 8.0, 2.1, 1.2 Hz, 1H), 7.59
(t, J = 7.8 Hz, 1H), 7.54–7.47 (m, 2H), and 7.43 (d, J = 8.5 Hz, 2H). 13C‐
NMR (101 MHz, DMSO‐d6) δ 188.4, 161.9, 155.8, 142.6, 138.2,
137.5, 135.5, 134.3, 134.2, 132.2, 131.4, 131.2, 130.8 (2C), 130.7,
128.9, 128.5 (2C), 128.1, 123.9, and 121.9 (2C). Q‐TOF LC/MS:
381.3080 ([M+H]+, C22H15Cl2NO+; calc. 380.0604).
(2E)‐3‐(4‐Nitrophenyl)‐1‐(3‐{[(1E)‐(4‐nitrophenyl)methylene]amino}‐
phenyl)prop‐2‐en‐1‐one (3i)
Yellow solid. Yield: 80%, m.p.: 213–216°C. IR (KBr, cm−1): 3,101,
3,075, 2,960, 2,884, 2,851, 1,662, 1,625, 1,610, 1,593, 1,572, 1,513,
1,489, 1,430, 1,333, 1,316, 1,290, 1,245, 1,206, 1,151, 1,103, 988,
850, 838, 754, 688, 677, 621, and 483. 1H‐NMR (400 MHz, DMSO‐
d6) δ 8.93 (s, 1H), 8.41 (d, J = 8.7 Hz, 2H), 8.30 (d, J = 8.8 Hz, 2H),
8.27–8.20 (m, 5H), 8.16–8.11 (m, 2H), 7.88 (d, J = 15.6 Hz, 1H), and
7.70–7.66 (m, 2H). 13C‐NMR (101 MHz, DMSO‐d6) δ 189.1, 161.0,
151.8, 149.5, 148.6, 142.0, 141.8, 141.6, 138.8, 130.6 (2C), 130.5,
130.3 (2C), 126.9, 126.4, 124.6 (2C), 124.4 (2C), 122.4, and 121.7.
Q‐TOF LC/MS: 402.3735 ([M+H]+, C24H15F6NO+; calc. 402.1084).
(2E)‐3‐(3‐Bromophenyl)‐1‐(4‐{[(1E)‐(3‐bromophenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (5c)
Yellow solid. Yield: 80%, m.p.: 130–132°C. IR (KBr, cm−1): 3,058,
3,027, 2,903, 1,655, 1,625, 1,585, 1,559, 1,515, 1,468, 1,416,
1,356, 1,324, 1,265, 1,217, 1,167, 1,068, 1,024, 975, 969, 956,
889, 826, 778, 670, 661, 592, and 566. 1H‐NMR (400 MHz, DMSO‐
d6) δ 8.65 (s, 1H), 8.25 (d, J = 8.6 Hz, 2H), 8.21 (t, J = 1.7 Hz, 1H),
8.13–8.10 (m, 1H), 8.06 (d, J = 15.6 Hz, 1H), 7.96–7.92 (m, 1H),
7.84 (d, J = 7.8 Hz, 1H), 7.74 (ddd, J = 8.0, 2.1, 1.0 Hz, 1H), 7.68
(d, J = 15.6 Hz, 1H), 7.60 (ddd, J = 8.0, 1.9, 0.8 Hz, 1H), 7.48
(t, J = 7.8 Hz, 1H), and 7.38 (dt, J = 4.1, 3.6 Hz, 3H). 13C‐NMR
(101 MHz, DMSO‐d6) δ 188.4, 161.8, 155.8, 142.6, 138.5, 137.8,
135.5, 135.0, 133.6, 131.8, 131.7, 131.5, 131.3, 130.8 (2C), 128.9,
128.5, 123.9, 122.9, 122.7, and 121.9 (2C). Q‐TOF LC/MS:
468.4180 ([M+H]+, C22H15Br2NO+; calc. 467.9593).
(2E)‐3‐(2‐Thienyl)‐1‐(3‐{[(1E)‐2‐thienylmethylene]amino}phenyl)‐
prop‐2‐en‐1‐one (3j)
Brown viscous oil. Yield: 79%. IR (KBr, cm−1): 3,098, 3,071, 2,960,
2,885, 1,654, 1,610, 1,568, 1,509, 1,417, 1,362, 1,304, 1,277, 1,209,
1,152, 1,039, 1,025, 963, 916, 822, 793, 698, 582, and 482. 1H‐NMR
(400 MHz, CDCl3) δ 8.60 (s, 1H), 7.94 (d, J = 15.3 Hz, 1H), 7.86–7.78
(m, 2H), 7.54–7.48 (m, 3H), 7.42–7.38 (m, 2H), 7.35–7.29 (m, 2H),
7.14–7.10 (m, 1H), and 7.07–7.04 (m, 1H). 13C‐NMR (101 MHz, CDCl3)
δ 189.5, 154.1, 151.7, 142.3, 140.3, 139.1, 137.4, 133.0, 132.3, 130.9,
129.5, 129.1, 128.4, 127.9, 125.9, 125.6, 120.7, and 120.5. Q‐TOF
LC/MS: 324.064 ([M+H]+, C18H13NOS2+; calc. 324.051).
(2E)‐3‐(4‐Fluorophenyl)‐1‐(4‐{[(1E)‐(4‐fluorophenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (5d)[36]
Yellow solid. Yield: 78%, m.p.: 141–143°C (Lit: 156.37°C).[36] IR (KBr,
cm−1): 3,043, 2,981, 2,921, 2,878, 1,656, 1,624, 1,581, 1,562, 1,506,
1,414, 1,335, 1,321, 1,291, 1,228, 1,213, 1,159, 1,089, 1,022, 1,008,
987, 889, 830, 815, 783, 672, 649, 535, 512, and 497. 1H‐NMR
(400 MHz, DMSO‐d6) δ 8.69 (s, 1H), 8.26 (d, J = 8.6 Hz, 2H), 8.09–7.94
(m, 5H), 7.78 (d, J = 15.6 Hz, 1H), 7.47–7.37 (m, 4H), and 7.33
(t, J = 8.9 Hz, 2H). 13C‐NMR (101 MHz, DMSO‐d6) δ 188.4, 164.8
(d, J = 250.3 Hz), 163.9 (d, J = 249.0 Hz), 161.8, 156.1, 143.1, 132.9
(d, J = 2.9 Hz), 132.0 (d, J = 3.2 Hz), 131.9 (d, J = 9.1 Hz, 2 C), 131.8
(d, J = 8.6 Hz, 2 C), 135.4, 130.6 (2C), 122.37 (d, J = 2.3 Hz), 121.8
(2C), 116.6 (d, J = 22.0 Hz, 2C), and 116.4 (d, J = 21.7 Hz, 2 C). Q‐TOF
LC/MS: 348.1317 ([M+H]+, C22H15F2NO+; calc. 348.1194).
(2E)‐3‐(3‐Fluorophenyl)‐1‐(4‐{[(1E)‐(3‐fluorophenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (5a)
Yellow solid. Yield: 82%, m.p.: 132–135°C. IR (KBr, cm−1): 3,062, 3,048,
2,968, 1,659, 1,628, 1,603, 1,579, 1,557, 1,485, 1,443, 1,412, 1,338,
1,296, 1,243, 1,207, 1,172, 1,139, 1,031, 971, 943, 876, 828, 775,
737, 680, 661, 518, and 443. 1H‐NMR (400 MHz, DMSO‐d6) δ 8.72
(d, J = 0.9 Hz, 1H), 8.29 (d, J = 8.6 Hz, 2H), 8.10 (d, J = 15.6 Hz, 1H),
7.94–7.87 (m, 1H), 7.86–7.81 (m, 1H), 7.80–7.70 (m, 3H), 7.62 (td, J = 8.0,
5.9 Hz, 1H), 7.52 (td, J = 8.0, 6.2 Hz, 1H), 7.48–7.40 (m, 3H), and
7.36–7.26 (m, 1H). 13C‐NMR (101 MHz, DMSO‐d6) δ 188.4, 163.0
(d, J = 243.4 Hz), 162.9 (d, J = 244.5 Hz), 162.1 (d, J = 3.0 Hz), 155.8, 142.9
(d, J = 2.8 Hz), 138.6 (d, J = 7.4 Hz), 137.8 (d, J = 8.0 Hz), 135.5, 131.6
(d, J = 8.2 Hz), 131.4 (d, J = 8.4 Hz), 130.7 (2 C), 126.2 (d, J = 2.6 Hz),
126.0 (d, J = 2.8 Hz), 123.9, 121.9 (2C), 119.4 (d, J = 21.5 Hz), 117.8
(d, J = 21.4 Hz), 115.2 (d, J = 22.2 Hz), and 115.2 (d, J = 22.0 Hz). Q‐TOF
LC/MS: 348.1342 ([M+H]+, C22H15F2NO+; calc. 348.1194).
(2E)‐3‐(4‐Methoxyphenyl)‐1‐(4‐{[(1E)‐(4‐methoxyphenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (5e)[37]
Yellow solid. Yield: 79%, m.p.: 140–142°C (Lit: 148–149°C).[37] IR
(KBr, cm−1): 3,061, 3,013, 2,959, 2,911, 2,839, 1,650, 1,625, 1,600,
1,587, 1,571, 1,508, 1,439, 1,415, 1,363, 1,303, 1,244, 1,165, 1,109,
1,075, 1,026, 990, 855, 834, 818, 721, 671, 583, 543, and 531. 1H‐
NMR (400 MHz, DMSO‐d6) δ 8.60 (s, 1H), 8.22 (d, J = 8.3 Hz, 2H),
7.98–7.82 (m, 5H), 7.75 (d, J = 15.5 Hz, 1H), 7.36 (d, J = 8.3 Hz, 2H),
7.10 (d, J = 8.6 Hz, 2H), 7.03 (d, J = 8.6 Hz, 2H), 3.86 (s, 3H), and 3.83
(s, 3H). 13C‐NMR (101 MHz, DMSO‐d6) δ 188.3, 162.8, 162.1, 161.8,
156.4, 144.2, 135.3, 131.4 (2C), 131.3 (2C), 130.5 (2C), 129.2, 127.9,
121.7 (2C), 119.9, 114.9 (2C), 114.8 (2C), 56.0, and 55.9. Q‐TOF
LC/MS: 254.1303 ([M+H]+, [C24H21NO3+–C8H8O2]; calc. 372.159)
(2E)‐3‐(3‐Chlorophenyl)‐1‐(4‐{[(1E)‐(3‐chlorophenyl)methylene]‐
amino}phenyl)prop‐2‐en‐1‐one (5b)[35]
Yellow solid. Yield: 81%, m.p.: 128–130°C. IR (KBr, cm−1): 3,046,
2,894, 1,659, 1,601, 1,590, 1,565, 1,473, 1,420, 1,411, 1,365, 1,333,
1,308, 1,220, 1,202, 1,194, 1,167, 1,098, 1,073, 978, 906, 832, 780,
724, 679, 665, 563, and 430. 1H‐NMR (400 MHz, DMSO‐d6) δ 8.71

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The expected mass could not be observed due to the hydrolysis of
the imine structure in the HPLC column.
ORCID
Ümit M. Koçyiğit
Hayreddin Gezegen
Parham Taslimi
http://orcid.org/0000-0001-8710-2912
http://orcid.org/0000-0003-3602-7400
http://orcid.org/0000-0002-3171-0633
(2E)‐3‐(3‐Thienyl)‐1‐(4‐{[(1E)‐3‐thienylmethylene]amino}phenyl)‐
prop‐2‐en‐1‐one (5f)
Yellow solid. Yield: 83% m.p.: 120–123°C. IR (KBr, cm−1): 3,096,
3,075, 2,975, 2,884, 1,653, 1,632, 1,598, 1,577, 1,533, 1,510, 1,439,
1,336, 1,318, 1,279, 1,242, 1,215, 1,172, 1,157, 1,132, 1,026, 1,007,
970, 864, 830, 781, 691, 617, 599, and 575. 1H‐NMR (400 MHz,
DMSO‐d6) δ 8.66 (s, 1H), 8.32–8.25 (m, 1H), 8.22 (d, J = 8.4 Hz, 2H),
8.13 (d, J = 2.7 Hz, 1H), 7.88–7.76 (m, 3H), 7.73–7.64 (m, 3H), and
7.37 (d, J = 8.4 Hz, 2H). 13C‐NMR (101 MHz, DMSO‐d6) δ 188.7,
157.3, 156.3, 140.8, 138.9, 138.1, 135.3, 133.8, 131.1, 130.5, 128.5,
128.2, 126.8, 125.9, 122.0, and 121.7. Q‐TOF LC/MS: 324.069 ([M
+H]+, C18H13NOS2+; calc. 324.051).
REFERENCES
[1] F. Lunardi, M. Guzela, A. T. Rodrigues, R. Corrêa, I. Eger‐Mangrich,
M. Steindel, E. C. Grisard, J. Assreuy, J. B. Calixto, A. R. Santos, An-
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ACKNOWLEDGMENTS
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This study is supported by the Scientific Research Project Fund of
Sivas Cumhuriyet University under the project number SHMYO‐013.
1H‐NMR, 13C‐NMR, and Q‐TOF LC/MS analyses of the compounds
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CONFLICTS OF INTEREST
The authors declare that there are no conflicts of interest.

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How to cite this article: Koçyiğit ÜM, Gezegen H, Taslimi P.
Synthesis, characterization, and biological studies of chalcone
derivatives containing Schiff bases: Synthetic derivatives for the
treatment of epilepsy and Alzheimer's disease. Arch Pharm.
2020;e2000202. https://doi.org/10.1002/ardp.202000202
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