Synthesis, characterization, and antioxidant activity of heterocyclic Schiff bases

Article abstract of DOI:10.1002/jccs.202000161

Schiff base derivatives have gained great importance due to revealing a great number of biological properties. Schiff bases were synthesized by treatment of 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (1) with various aldehydes in methanol at reflu

Full text of DOI:10.1002/jccs.202000161

Received: 15 April 2020
Revised: 10 July 2020
Accepted: 4 August 2020
DOI: 10.1002/jccs.202000161
A R T I C L E
Synthesis, characterization, and antioxidant activity of
heterocyclic Schiff bases
Hakan Kizilkaya1 | Bes¸ir Dag1 | Tarik Aral1 | Nusret Genc2
Ramazan Erenler2
|
1Department of Chemistry, Faculty of Arts
Abstract
and Sciences, Batman University, Batman,
Turkey
Schiff base derivatives have gained great importance due to revealing a great
number of biological properties. Schiff bases were synthesized by treatment of
4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (1) with various alde-
hydes in methanol at reflux. In addition, diamine was reacted with an alde-
hyde to yield the corresponding Schiff bases. The structures of synthesized
Schiff bases were elucidated by spectroscopic methods such as microanalysis,
1H-NMR, 13C-NMR, and FTIR. Antioxidant activities of synthesized
Schiff bases were carried out using different antioxidant assays such as
1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH•) scavenging, 2,20-azino-bis
(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, and reduc-
ing power activity. (E)-4-((1H-indol-3-yl)methyleneamino)-1,5-dimethyl-2-phe-
nyl-1H-pyrazol-3(2H)-one (3), (E)-1,5-dimethyl-4-((2-methyl-1H-indol-3-yl)
methyleneamino)-2-phenyl-1H-pyrazol-3(2H)-one (5), (E)-1,5-dimethyl-2-phe-
nyl-4-(thiophen-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one (7), (E)-1,5-dimethyl-
2-phenyl-4-(quinolin-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one (9), (1S,2S,
N1,N2)-N1,N2-bis((1H-indol-3-yl)methylene)cyclohexane-1,2-diamine (11),
and (1S,2S,N1,N2)-N1,N2-bis((2-methyl-1H-indol-3-yl)methylene)cyclohex-
ane-1,2-diamine (12) were synthesized in high yields. Compound 5 displayed
a good ABTS•+ activity. Compound 3 revealed the outstanding activity in all
assays. Compound 7 has the best-reducing power ability in comparison to
other synthesized compounds. Although compounds 5, 11, 12 are new, com-
pounds 3, 7, 9 are known. Due to revealing a good antioxidant activity, the
synthesized compounds (3, 5, 7) have the potential to be used as synthetic
antioxidant agents.
2Department of Chemistry, Faculty of Arts
and Sciences, Tokat Gaziosmanpasa
University, Tokat, Turkey
Correspondence
Ramazan Erenler, Department of
Chemistry, Faculty of Arts and Sciences,
Tokat Gaziosmanpasa University, 60250
Tokat, Turkey.
Email: rerenler@gmail.com
K E Y W O R D S
antioxidant activity, chromatography, heterocyclic, Schiff base, spectroscopy, synthesis
1 | INTRODUCTION
of their applications nowadays. The SBs, defined by an
imine or azomethine (−CH = N−) group, are mostly syn-
The synthesis of aromatic compounds is of great impor-
tance due to the wide variety of uses.[1–8] The Schiff bases
(SBs) have gained great interest owing to the wide range
thesized by the condensation reaction of carbonyl com-
pounds (aldehyde or ketone) with compounds consisting
of amine moiety.[9] Due to the electron-donating ability,
J Chin Chem Soc. 2020;1–6.
http://www.jccs.wiley-vch.de
© 2020 The Chemical Society Located in Taipei & Wiley-VCH GmbH
1

2
KIZILKAYA ET AL.
SBs could be used in the field of coordination chemistry
extensively.[10] SBs are among the most chiefly used
2 | RESULTS AND DISCUSSION
organic compounds, revealing
a
wide range of
2.1 | Synthesis and characterization
applications, such as electroluminescent effects,[11] fluo-
rescence properties,[12] nonlinear optical properties,[13]
chemosensory.[14] In addition, SBs and their metal
complexes have showed a large variety of biological
activity in recent research, including anticancer,
antioxidant,[15] antibacterial, antibiofilm, anti-inflam-
matory, hemocompatibility, cytotoxic,[16] pesticidal,
nematicidal activities.[17] Due to the flexible and stereo-
electronic structures, most SBs are attractive ligants to
The synthetic pathways for the synthesis of
corresponding compounds were given (3, 5, 7, 9) in
Schemes 1 and 2 (11, 12). The treatment of 4-amino-1,-
5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one
(1)
with
indole-3-carbaldehyde (2) at 80ꢀC in MeOH yielded the
corresponding compound 1,5-dimethyl-4-[(3-indoleyl)-
methyleneamino]-2- phenyl-1H-pyrazol-3(2H)-one (3).[23]
IR spectrum indicated the vibration bands for C O at
1,624 cm−1 and for NH at 3,135 cm−1 confirmed the
form stable complexes with most transition metals[18]
.
1
SBs complexes reveal considerable catalytic activities for
many organic transformations.[19]
corresponding structure. In the H NMR spectrum, the
NH signal was observed at 11.60 ppm as a singlet. Ole-
finic proton gave the signal at 9.78 ppm as a singlet due
to the lack of neighbor proton. Because of the deshielding
effect, olefinic proton shifted downfield. Aromatic proton
signal at indole ring appeared at 8.45 ppm as a doublet
with a coupling constant of 8.0 Hz and other aromatic
protons gave the signals between 7.87 and 7.18 ppm. The
methyl groups bounded to nitrogen and carbon gave the
signals at 3.10 and 2.48 ppm, respectively. In the 13C
NMR spectrum, observation of 18 peaks confirmed the
proposed structure. The carbonyl peak appeared at
160.9 ppm. The methyl carbon bonded to nitrogen and
carbon gave the signals at 36.5 ppm and 10.5 ppm,
respectively.
Reactive oxygen species (ROS) are free radicals pro-
duced during the oxidative metabolism. ROS can attack
the nucleic acid, lipids, proteins, polyunsaturated fatty
acids, and carbohydrate and induce their oxidation that
may lead to oxidative damage such as protein change,
membrane dysfunction, enzymatic inactivation, and
break of DNA strains. Hence, ROS should be scavenged
by cellular constituents. An antioxidant can inhibit or
delay the oxidation of other molecules. Antioxidants are
capable of inhibiting the formation of free radicals as well
as delaying the lipid peroxidation leading to the deterio-
ration of food and pharmaceutical products while
processing and storage stage. Antioxidants can protect
the human body from ROS. Antioxidants have been
extensively used for food to prevent radical chain reac-
tions causing the deterioration of food.[20–22]
Treatment of 4-aminopyridine (1) with methylindole-
3-caroboxaldehyde (4) in methanol at 80ꢀC resulted in
the formation of 1,5-dimethyl-4-((2-methyl-1H-indol-3-yl)
SCHEME 1 The synthesis
of Schiff bases

KIZILKAYA ET AL.
3
SCHEME 2 The synthesis
of Schiff bases by treatment of
diamine with aldehydes
methyleneamino)-2-phenyl-1H-pyrazol-3(2H)-one
(5).
The reaction of 2-methyl-indole-3-carbaldehyde
(4) with (1S,2S)-cyclohexane-1,2-diamine (10) afforded
Spectroscopic analyses revealed the proposed compound.
In the IR spectrum, the NH vibration band was observed
the
(1S,2S,N1,N2)-N1,N2-bis((2-methyl-1H-indol-3-yl)
at 3,240 cm−1. C O signal was observed at 1,636 cm−1
.
methylene)cyclohexane-1,2-diamine (12). NH vibration
band was observed at 2,931 cm−1 in the IR spectrum. In
the 1H NMR spectrum, the NH signal appeared at δ 11.15
as a singlet. The appearance of 10 protons signals at aro-
matic regions accorded to the structure. The aliphatic
10 protons resonated at upfield due to the strong
shielding effect. The methyl groups gave the peak at δ
2.32 as a singlet. In the 13C NMR spectrum, signals of
four quaternary carbons, five methine carbons, and two
methylene carbons supported the proposed symmetric
structure.
1
In the H NMR spectrum, the integration of protons as
well as chemical shifts accord with the structure. The sig-
nal observed at δ 11.49 ppm belonged to the NH. The ole-
finic proton displayed the signal at 9.85 ppm as a singlet.
The chemical shifts of aromatic protons accord with the
structure. The methyl groups resonated at δ 3.10 ppm, δ
2.54 ppm, δ 2.47 ppm. Nineteen peaks in the 13C NMR
spectrum confirmed the proposed structure 5.
Treatment of 4-aminopyridine (1) with thiophene-
2-carbaldehyde (6) in methanol at 80ꢀC resulted in the
formation
of
1,5-dimethyl-2-phenyl-4-(thiophen-
2-ylmethyleneamino)-1H-pyrazol-3(2H)-one (7).[24] In
the IR spectrum, the carbonyl signal appeared at
2.2 | Antioxidant activity
1
1,636 cm−1. In the H NMR spectrum, the signal of the
olefinic proton was observed at 9.88 ppm as a singlet.
The other protons gave the signals at the expected loca-
tion. Fourteen peaks in the 13C spectrum confirmed the
proposed structure (7).
Antioxidant activity of synthesized compounds was
investigated using the 1,1-diphenyl-2-picryl-hydrazyl free
radical
(DPPH•)
scavenging,
2,20-azino-bis
(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical
scavenging, and reducing power activity. The compound
3 revealed the most DPPH activity (48.49 0.13) among
the compounds. In addition, it displayed the excellent
ABTS (15.09 0.15) scavenging activity. The compound
5 (17.89 0.1), RA5 (27.97 0.15) showed the consider-
able ABTS scavenging effect also. In concerning reducing
power, the compound 7 (4.55 0.02) and compound
3 (4.084 0.015) have significant reducing power effect
compared to the standards BHA (9.035 0.186)
(Table 1).
The reaction of 4-aminopyridine (1) with quinoline-
2-carbaldehyde (8) in MeOH at 80ꢀC afforded the
1,5-dimethyl-2-phenyl-4-(quinolin-2-ylmethyleneamino)-
1H-pyrazol-3(2H)-one (9).[25] IR spectrum displayed the
1
strong vibration bands for C O at 1,649 cm−1. In the H
NMR spectrum, the chemical shifts were observed at the
expected location. The observation of 19 peaks in the 13C
NMR spectrum accords with the structure.
The treatment of indole-3-carbaldehyde (2) with
trans-cyclohexane-1,2-diamine (10) in ethanol at 80ꢀC
yielded the (1S,2S,N1,N2)-N1,N2-bis((1H-indol-3-yl)
methylene)cyclohexane-1,2-diamine (11). In the IR spec-
trum, the NH vibration band was observed at 2,925 cm−1
.
3 | EXPERIMENTAL
3.1 | General procedure
1H- and 13C-NMR spectra revealed that the molecule has
C2 symmetry. In the 1H NMR spectrum, the signal
observed at δ: 11.31 belonged to the NH protons. The
other chemical shifts were observed at expected values
that accorded to the structure 11. The observation of
12 peaks in the 13C NMR spectrum suited with the
structure.
NMR spectra were recorded on a Bruker spectrometer
with 1H NMR at 400 MHz, 13C NMR at 100 MHz. The 1H
NMR chemical shifts were measured relative to CDCl3 as
the internal reference (CDCl3: δ 7.26, DMSO-d6: δ 2.5).

4
KIZILKAYA ET AL.
TABLE 1 Antioxidant activity of synthesized compounds
3.1.2 | Synthesis of 1,5-dimethyl-
4-[(2-methyl-1H-indol-3-yl)
methyleneamino]-2-phenylpyrazol-
3-one (5)
Compounds
DPPHa
ABTSa
FRAPb
3
48.49 0.13
91.83 0.28
616.36 2.04
724.79 2.06
591.62 3.16
593.66 3.54
11.81 0.42
5.19 0.08
5.34 0.06
15.09 0.15
17.89 0.1
32.03 0.16
27.97 0.15
45.53 0.17
44.23 0.28
10.34 0.07
7.14 0.09
6.92 0.04
4.084 0.015
3.355 0.024
4.55 0.02
3.535 0.204
0.227 0.007
0.328 0.007
5.288 0.187
9.035 0.186
-
5
7
To a solution of 4-aminopyridine (1) (2.0 g, 10.0 mmol) in
dry methanol (30 ml) was added
a
solution of
9
2-methylindole-3-caroboxaldehyde (4) (1.6 g, 10.0 mmol) in
dry methanol (20 ml) slowly for 100 min via micropipette.
The reaction mixture was stirred for overnight at reflux
temperature. The reaction progress was monitored by TLC.
After cooling to room temperature, the solid part was fil-
tered by filtering flask under vacuum by adding cold meth-
anol to yield the desired solid product (5) (2.8 g, 82%). Mp:
267–268ꢀC. Anal. Calcd for C21H20N4O: C, 73.23; H, 5.85.
Found: C, 73.21; H, 5.82. FTIR: υ/cm−1 3,240, 3,053, 2,900,
1,636, 1,591, 1,571, 1,491, 1,469, 1,452, 1,432, 1,360, 1,347,
1,279, 1,243, 1,132, 1,099, 1,068, 1,018, 962, 928, 903, 870,
11
12
BHT
BHA
Trolox
aIC50 (μg/ml).
bmmol TE/g compound.
TLC was carried out on alumina plates (60F254). UV-260
Shimadzu spectrometer was used for UV analysis. Silica
gel (Kiesegel 60, 0.063–0.200 mm, Merck) was used for
column chromatography. Melting points were deter-
1
851, 764, 745, 720, 692 (Figure S10). H NMR (400 MHz,
DMSO-d6) δ 11.49 (s, 1H, NH), 9.85 (s, 1H), 8.35 (t,
J = 4.8 Hz, 1H), 7.52 (t, J = 7.2 Hz, 2H), 7.41 (d,
J = 8.2 Hz, 2H), 7.34 (t, J = 6.2 Hz, 2H), 7.12 (t, J = 4.8 Hz,
2H), 3.10 (s, 3H), 2.54 (s, 3H), 2.47 (s, 3H) (Figure S6). 13C
NMR (100 MHz, DMSO-d6) δ: 161.0, 152.2, 151.2, 141.6,
136.3, 135.5, 129.5, 126.7, 126.3, 124.3, 122.1, 121.6, 120.9,
119.5, 111.9, 111.3. 36.5, 12.0, 10.5 (Figure S9).
mined with
a Biichi B-540 apparatus and were
uncorrected. IR analyses were executed on Jasco
FT/IR47700 spectrometer. All chemicals and solvents for
reactions and antioxidant assays were supplied from
E. Merck (Darmstadt, Germany).
3.1.1 | Synthesis of 4-(1H-Indol-
3-ylmethyleneamino)-1,5-dimethyl-
2-phenyl-1H-pyrazol-3(2H)-one (3)
3.1.3 | Synthesis of (E)-1,5-dimethyl-
2-phenyl-4-(thiophen-
2-ylmethyleneamino)-1H-pyrazol-3(2H)-
one (7)
A solution of 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-
3(2H)-one (1) (2.03 g, 0.010 mol) in methanol (20 ml)
was prepared and started to reflux, indole-3-carbaldehyde
(2) (1.45 g, 0.010 mol) was added to this solution for
72 min during the 4 min periods. After the completion of
the reaction, solid product was filtered and dried. Yield:
2.65 g, 80%; mp: 280–282ꢀC. Anal. Calcd for
C20H18N4O: C, 72.71; H, 5.49. Found: C, 72.77; H, 5.51.
FTIR: υ/cm−1 3,135, 3,104, 3,037, 2,976, 2,920, 2,878,
1,624, 1,599, 1,583, 1,571, 1,524, 1,496, 1,482, 1,455, 1,437,
1,378, 1,359, 1,303, 1,284, 11,244, 1,141, 1,115, 1,003,
A solution of 4-aminopyridine (1) (2.0 g, 10.0 mmol) in
dry methanol (10 ml) was started to reflux. A solution of
thiophene-2-carbaldehyde (6) (1.12 g, 10 mmol) in MeOH
(10 ml) was added to this reflux solution every 4 min and
addition was completed for 80 min. After completion of
the reaction for 12 hr, the reaction mixture was cooled to
room temperature then the solid product was filtered and
dried (2.60 g, 87%). Mp: 170–171ꢀC. Anal. Calcd for
C16H15N3OS: C, 64.62; H, 5.08. Found: C, 64.67; H, 5.11.
FTIR: υ/cm−1 3,066, 2,958, 1,898, 1,814, 1,636, 1,573,
1,560, 1,514, 1,485, 1,454, 1,422, 1,410, 1,376, 1,340, 1,306,
1,211, 1,126, 1,074, 1,048, 1,024, 950, 932, 915, 867,
849, 765, 754, 743, 704, 691 (Figure S14). 1H NMR
(400 MHz, CDCl3) δ: 9.88 (s, 1H), 7.49 (m, 2H), 7.41 (m,
3H), 7.38 (d, 3.6 Hz, 1H), 7.33 (t, J = 7.3 Hz, 1H), 7.09
(dd, J = 3. 6 Hz, 4.9 Hz), 3.15 (s, 3H, N-CH3), 2.47 (s, 3H,
Me) (Figure S11). 13C NMR (100 MHz, CDCl3) δ: 160.9,
151.7, 150.8, 145.1, 134.8, 130.4, 129.2, 128.4, 127.7, 126.9,
124.4, 118.4, 35.9, 10.1 (Figure S13).
1
962, 934, 884, 862, 785 (Figure S5). H NMR (400 MHz,
DMSO-d6) δ: 11.60 (s, 1H, NH), 9.78 (s, 1H), 8.45 (d,
J = 8.0 Hz, 1H), 7.86 (d, J = 4.0 Hz, 1H), 7.52 (t,
J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 1H), 7.41 (d,
J = 8.0 Hz, 2H), 7.34 (t, J = 8.0 Hz, 1H), 7.20 (m, 2H),
3.10 (s, 3H), 2.48 (s, 3H) (Figure S1). 13C NMR (100 MHz,
DMSO-d6) δ: 160.9, 152.9, 151.4, 137.8, 135.5, 132.0,
129.5, 126.8, 125.2, 124.4, 123.0, 122.6, 121.1, 119.0, 116.4,
112.3, 36.5, 10.5 (Figure S3).

KIZILKAYA ET AL.
5
3.1.4 | Synthesis of (E)-1,5-dimethyl-
2-phenyl-4-(quinolin-2-ylmethyleneamino)-
1H-pyrazol-3(2H)-one (9)
3.1.6 | (1S,2S,N1,N2)-N1,N2-bis
((2-methyl-1H-indol-3-yl)methylene)
cyclohexane-1,2-diamine (12)
A solution of 4-aminopyridine (1) (2.0 g, 10.0 mmol) in
dry methanol (10 ml) was started to reflux. A solution of
quinoline-2-carbaldehyde (8) (1.57 g, 10 mmol) in MeOH
(10 ml) was added to this reflux solution every 4 min and
addition was completed for 100 min. After completion of
the reaction for 12 hr, the reaction mixture was cooled to
room temperature then the solid product was filtered and
dried (1.91 g, 56%). Mp: 220–221ꢀC. Anal. Calcd for
C21H18N4O: C, 73.67; H, 5.30. Found: C, 73.69; H, 5.33.
FTIR: υ/cm−1 3,040, 2,929, 1,948, 1,650, 1,588, 1,563,
1,481, 1,453, 1,411, 1,376, 1,356, 1,300, 1,231, 1,131, 1,113,
1,072, 1,037, 1,020, 954, 891, 863, 826, 763, 700
To a solution of 2-methylindoline-3-carbaldehyde (4)
(3.2 g, 20 mmol) in dry methanol (15 ml) was added trans-
1,2-cyclohexane diamine 10 (1.1 g, 10 mmol) in dried
methanol (10 ml) slowly via micropipette for 120 min. The
reaction mixture was stirred for overnight at reflux tem-
perature. The reaction progress was monitored by TLC for
consumption of the starting material. After cooling to
room temperature, the mixture was kept in the fridge for
2 hr at +4ꢀC. The yellow solid was filtered under vacuum
and washed with cold methanol to yield the product
(2.60 g, 68%). mp: 205–206ꢀC. Anal. Calcd for
C26H28N4: C, 78.75; H, 7.12. Found: C, 78.77; H, 7.09.FTI
R: υ/cm−1 3,393, 2,931, 2,913, 2,856, 2,808, 2,159, 1,633,
1,577, 1,555, 1,488, 1,466, 1,435, 1,382, 1,304, 1,243, 1,179,
1,157, 1,137, 1,096, 1,034, 968, 940, 920, 862, 851, 839,
1
(Figure S19). H NMR (400 MHz, DMSO-d6) δ: 9.75 (s,
1H), 8.42 (d, J = 8.5 Hz, 1H), 8.30 (d, J = 8.6 Hz, 1H),
8.06 (d, J = 8.5 Hz, 1H), 8.01 (d, J = 8.1 Hz, 1H), 7.80 (m,
1H), 7.64 (t, J = 7.2 Hz, 1H), 7.58 (m, 2H), 7.43 (m, 3H),
3.27 (s, 3H), 2.56 (s, 3H) (Figure S15). 13C NMR
(100 MHz, CDCl3) δ: 159.6, 156.8, 154.4, 152.9, 148.0,
136.8, 134.8, 130.4, 129.7, 129.5, 128.5, 128.4, 127.9, 127.6,
125.8, 117.6, 115.9, 35.4, 10.2 (Figure S17).
1
814, 742 (Figure S27). H NMR (400 MHz, DMSO-d6) δ:
11.15 (s, 2H, 2NH), 8.44 (s, 2H), 8.16 (d, J = 4.0 Hz, 2H),
7.22 (d, J = 8.0 Hz, 2H), 7.02 (m, 4H), 3.20 (d, J = 4.0 Hz,
2H), 2.32 (s, 6H), 1.87 (brs, 4H), 1.74 (brs, 2H), 1.50 (brs,
2H) (Figure S23). 13C NMR (100 MHz, DMSO-d6) δ: 154.4,
140.0, 135.8, 126.8, 121.7, 121.5, 120.2, 110.9, 110.4, 75.0,
49.1, 33.9, 24.9 (Figure S26).
3.1.5 | Synthesis of (1S,2S,N1,N2)-N1,N2-
bis((1H-indol-3-yl)methylene)cyclohexane-
1,2-diamine (11)
4 | ANTIOXIDANT ASSAYS
4.1 | ABTS+• scavenging assay
To a solution of indole-3-carbaldehyde (2) (3.19 g,
22 mmol) in dried methanol (20 ml) was added a solution
of trans-cyclohexane-1,2-diamine (10) (1.26 g, 11.0 mmol)
in methanol (10 ml) slowly via micropipette for 120 min
at 80ꢀC. The reaction mixture was stirred overnight at
reflux temperature. The reaction progress was moni-
tored by TLC. After cooling to room temperature, the
solvent was removed under reduced pressure to yield
the viscous oil, which was boiled in hexane (20 ml) then
chloroform (10 ml) was added to the solution to yield
the yellow solid (3.16 g, 78%). Mp: 199–201ꢀC (decom-
pose). Anal. Calcd for C24H24N4: C, 78.23; H, 6.57.
Found: C, 78.19; H, 6.55. FTIR: (υ/cm−1) 2,925, 2,853,
1,622, 1,577, 1,527, 1,499, 1,446, 1,387, 1,340, 1,325,
1,312, 1,294, 1,236, 1,132, 1,121, 1,090, 1,054, 1,006, 9 25,
The treatment of ABTS (2 mM) with potassium persulfate
(2.45 mM) yielded the formation of ABTS radical cation,
which was kept for 6 hr in dark at room temperature. After-
ward, ABTS•+ (1.0 ml) was treated with each compound
(3.0 ml) at different concentrations. The inhibition was calcu-
lated for each concentration relative to a blank absorbance.
ABTS•+ capacity was calculated by the given equation:
ABTS• + scavenging effect ð%Þ = ½ðA1 −A2Þ=A1ꢁ × 100
in which, A1 is ABTS•+ initial concentration and A2 is
ABTS•+ remaining concentration in the sample. The
[26]
results were calculated as IC50.
1
866, 822, 735 (Figure S22). H NMR (400 MHz, DMSO-
d6) δ: 11.31 (s, 2H, 2NH), 8.42 (s, 2H), 8.22 (d,
J = 8.0 Hz, 2H), 7.54 (s, 2H), 7.34 (d, J = 8.0 Hz, 2H),
7.17–7.00 (m, 4H), 3.25 (d, J = 8.7 Hz, 2H), 1.84 (d,
J = 8.0 Hz, 4H), 1.72 (d, J = 8.8 Hz, 2H), 1.50 (t,
J = 8.8 Hz, 2H) (Figure S20). 13C NMR (100 MHz,
DMSO-d6) δ 154.8, 137.3, 130.4, 125.6, 122.6, 122.3,
120.5, 115.1, 112.0, 74.8, 33.9, 24.8 (Figure S21).
4.2 | DPPH• free radical assay
DPPH• scavenging effect of compounds was carried out
by the reported procedure.[27] DPPH• solution (0.26 mM,
1.0 ml) was treated with the different concentrations of
compounds (3 ml, 2.0–60 μg/ml). The reaction was

6
KIZILKAYA ET AL.
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carried out at room temperature for 30 s. The absorbance
measurement was executed at 517 nm on a spectropho-
tometer. The DPPH• scavenging activity was calculated
using the equation:
DPPH• scavenging effect ð%Þ = ½ðA1 −A2Þ=A1ꢁ × 100
A1 is the absorbance of the control and A2 is the absor-
bance of the sample. The results were calculated as IC50.
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4.3 | Reducing power
Initially, Sodium phosphate buffer (0.2 M, pH 6.7) was pre-
pared. Potassium ferricyanide [K3Fe(CN)6] (1.25 ml, 1%) was
reacted with compounds at different concentrations at 50ꢀC
for 30 min and the total volume was completed to 2.5 ml
with sodium phosphate buffer solution. The reaction mixture
was stirred for 20 min. Trichloroacetic acid (1.25 ml, 10%)
and FeCl3 (0.25 ml, 0.1%) were added to the reaction flask.
The absorbance measurement was carried out at 700 nm
with a spectrophotometer. The high absorbance value of the
reaction mixture indicated a high reducing capability.[28]
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5 | CONCLUSIONS
_
Elmastas, I. Telci, J. Sci. Food Agr. 2016, 96(3), 822.
[22] R. Erenler, S. Yilmaz, H. Aksit, O. Sen, N. Genc, M. Elmastas,
I. Demirtas, Rec. Nat. Prod. 2014, 8(1), 32.
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Three new (5, 11, 12) and three known (3, 7, 9) SBs were
synthesized efficiently in high yields. The addition of
aldehyde slowly into the reaction medium is important
for product yield. Due to revealing a good antioxidant
activity, the synthesized compounds (3, 5, 7) have the
potential to be used as synthetic antioxidant agents. Due
to the easy synthesis of corresponding compounds, fur-
ther physical and medicinal properties of corresponding
compounds should be investigated.
_
ORCID
[28] M. Elmastas, S. M. Celik, N. Genc, H. Aksit, R. Erenler, I.
Gulcin, Int. J. Food Prop. 2018, 21(1), 374.
Ramazan Erenler https://orcid.org/0000-0002-0505-
3190
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
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