KF/clinoptilolite nanoparticles as a novel catalyst for the green synthesis of chromens using three component reactions of 4-hydroxycoumarins: Study of antioxidant activity

Article abstract of DOI:10.1002/jccs.201800282

In this research, the green synthesis of chromen derivatives in good yields is described via three-component reactions of 4-hydroxycumarine, aldehydes or ketones, and methyl ketones in the presence of KF/clinoptilolite nanoparticles (KF/CP-NPs) under solv

Full text of DOI:10.1002/jccs.201800282

Received: 11 August 2018
Revised: 30 January 2019
Accepted: 1 February 2019
DOI: 10.1002/jccs.201800282
A R T I C L E
KF/clinoptilolite nanoparticles as a novel catalyst for the green
synthesis of chromens using three component reactions of
4-hydroxycoumarins: Study of antioxidant activity
Samanehsadat Sharifi1 | Malek Taher Maghsoudlou1 | Nourallah Hazeri1 |
Faramarz Rostami-Charati2
1Department of Chemistry, University of Sistan &
In this research, the green synthesis of chromen derivatives in good yields is
Baluchestan, Zahedan, Iran
2Department of Chemistry, Faculty of Science,
Gonbad kavous University, Gonbad, Iran
described via three-component reactions of 4-hydroxycumarine, aldehydes or
ketones, and methyl ketones in the presence of KF/clinoptilolite nanoparticles
(KF/CP-NPs) under solvent-free conditions at 50ꢀC in low time. The present meth-
odology suggests some advantages such as low reaction time, easy and simple pro-
cedure, green method, inexpensive catalyst, high yield of product, and existence of
different substrates for performing these reactions. In addition, it should be men-
tioned that antioxidant activity was studied for some prepared compounds, such as
4a–4d, by DPPH radical trapping and reducing potential tests of ferric ion and then
comparing results with TBHQ and BHT as synthetic antioxidants. In this study,
compounds 4c was shown to have moderate DPPH radical trapping, and com-
pounds 4b and 4d displayed good reducing power of ferric ion.
Correspondence
Malek Taher Maghsoudlou, Department of
Chemistry, University of Sistan &
Baluchestan, P. O. Box 98135-674,
Zahedan, Iran.
Email: mt_maghsoodlou@yahoo.com
Funding information
University of Sistan & Baluchestan Research
Council
KEYWORDS
aldehyde, chromenes, DPPH radical trapping, ferric ion, ketones,
KF/clinoptilolite nanoparticles
and catalyst, low costs, mild reaction conditions, and low
pollution.[5–7] The chemistry of heterocyclic compounds has
1
| INTRODUCTION
Multicomponent reactions are very significant in organic
synthesis because of the creation of carbon–carbon and
carbon–hetero atom bonds in one pot.[1–3] Some advantages
of these reactions include easy and clean procedures, pro-
ducing of high yield bond formation, consuming of low time
and energy, and low costs.[4] In the past few years, chemists
have been informed about the environmental conditions and
about performing the reaction in green conditions. There-
fore, they have attempted to develop new synthetic proce-
dures, reaction conditions, and materials that decrease the
dangers to persons and the environment. Organic solvents
are hazardous because they are frequently volatile liquids
and are regularly used. Therefore, in recent years, perform-
ing organic reactions under solvent-free conditions is of
interest because of high yields, easy separation of product
been studied in several fields, such as natural products, bio-
logically active agrochemicals, pharmaceutical agents, and
organic materials.[8] Chromenes are important heterocycles
with a broad range of biological activities,[9–14] such as anti-
cancer, anti-inflammatory, antimicrobial, and antihypergly-
cemic activities, along with the properties of
antineurodegenerative disorders such as Alzheimer's, Parkin-
son disease, and many more.[15–20] Pyrano[3,2-c]chromen-5
(4H)-ones are the promising class of oxygen-containing het-
erocyclic compounds that have a diversity of biologically
active products and have been shown to a broad series of
biological activities.[21] Therefore, the synthesis of the
pyrano[3,2-c]chromen-5(4H)-ones is very important in
organic synthesis. Some methods have been developed for
the synthesis of pyrano[3,2- c]chromen-5(4H)-ones.[22]
© 2019 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2019;1–9.
http://www.jccs.wiley-vch.de
1

2
SHARIFI ET AL.
However, these methods have problems such as relatively
long reaction time, difficult reaction conditions, high reac-
tion temperature, using toxic catalysts, and an organic sol-
vent. As a result, a new and efficient, environmentally
benign practical procedure and operational simplicity
method should be used for the synthesis of pyrano[3,2-c]
chromen-5(4H)-ones. Compounds, mainly because of their
redox properties and chemical structure, demonstrate antiox-
idant activity and have chief roles as middle metals chela-
tors, filling singlet and triplet oxygen molecules, besides the
negative effect of free radicals. Many of diseases such as
cardiovascular, inflammatory bowel syndrome, cancer,
aging, atherosclerosis, and Alzheimer's disease could be pre-
vented or decreased by employing of these
compounds.[23–27] Recently, medicinal chemists, food chem-
ists, and biologists have investigated and tested the new and
efficient procedure for the synthesis of antioxidant com-
pounds as a protecting tactic against these diseases.
KF/CP, which is used as a new natural and economical
solid base, has been synthesized from putting potassium
fluoride on clinoptilolite as a new natural and inexpensive
solid base system.[28–36] Clinoptilolite is a natural zeolite
with a high internal surface area. It is precious because of its
high replacing capability of cations, mainly for K+. There-
fore, more free fluoride anions act as a good base. In con-
trast, the preparation of clinoptilolite (KF/CP) is very easy
without the need for any preactivation.[23–25] Here, we report
a facile catalyst and green one-pot synthesis of pyrano[3,2-c]
chromen-5(4H)-ones via three-component reaction of
4-hydroxycumarine, aldehydes or ketones, and methyl
ketones under solvent-free conditions at 50ꢀC (Table 1).
2
| RESULTS AND DISCUSSION
The first step in these reactions is optimization of the reac-
tion conditions. For this reason, we selected the reaction
between 4-hydroxycumarine 1, acetophenone 2a, and benz-
aldehyde 3a as a model. To achieve the best conditions for
generating chromen derivatives 4a, we changed the solvent,
catalyst, amount of catalyst, and temperature until the best
outcome is achieved. The reaction was tested without a cata-
lyst and demonstrated that these reactions have a very low
yield without catalyst. Several catalysts, for example, CM-
ZnO, CuO-NPs, KF/CP-NPs, ZnO-NPs, and TiO2-NPs,
were tested to achieve the best catalyst (Table 2). In addi-
tion, some solvents, such as CH2Cl2, CH3CN, H2O, and tol-
uene, and solvent-free conditions were examined to select
the best solvent for these reactions. Different temperatures
were tested for the model reaction, and the results are shown
in the Table 2.
TABLE 1 Synthesis of pyrano[3,2-c]chromen-5(4H)-ones derivatives
R'
O
OH
R'''
O
O
R
R
KF/CP (10mol%)
Solvent-free, 50oC
+
R''
+
R''
CH3
R'
R'''
O
O
O
O
1
2
3
4
Entry
1
R
H
H
H
H
H
H
H
H
H
H
Me
Me
H
H
H
H
R0
R00
R000
H
Product (4)
Time (min)
Yielda (%)
90
Ph
Ph
Ph
Ph
Ph
4a
4b
4c
25
20
20
15
20
15
15
25
30
10
25
20
18
18
15
35
2
4-me-C6H4
H
87
3
3,4-OCH2OC6H3
4-NO2-C6H4
Ph
H
95
4
H
4d
4e
92
5
4-MeO-C6H4
4-Br-C6H4
4-cl-C6H4
4-me-C6H4
Ph
H
70
6
Ph
H
4f
75
7
4-cl-C6H4
4-cl-C6H4
Ph
H
4 g
4 h
4i
98
8
H
95
9
Me
H
85
10
11
12
13
14
15
16
Me
Ph
4j
90
Ph
Ph
H
4 k
4 L
4 m
4n
4o
4p
95
Ph
4-me-C6H4
3-MeO-C6H4
4-EtO-C6H4
Ph
H
90
4-Br-C6H4
4-Br-C6H4
Et
H
87
H
90
Me
H
70
tBu
4-MeO-C6H4
78
aIsolated yields

SHARIFI ET AL.
3
TABLE 2 Effect of solvent, catalyst, and temperature on the formation of
Compound 4a
Entry
1
Catalyst
-----
Solvent
CH2Cl2
Temp.
r.t.
r.t.
50
80
r.t.
50
r.t.
50
90
r.t.
50
90
r.t.
r.t.
50
r.t.
50
80
r.t.
50
80
r.t.
50
80
r.t.
50
50
r.t.
50
80
r.t.
50
50
50
50
80
50
50
50
50
80
50
50
50
50
80
Yield (%)
5
2
-----
H2O
H2O
-----
-----
-----
-----
10
3
-----
4
-----
H2O
5
-----
CH3CN
6
-----
CH3CN
7
-----
Toluene
Toluene
Toluene
Solvent-free
Solvent-free
Solvent-free
CH2Cl2
10
8
-----
-----
15
9
-----
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
----
10
10
FIGURE 1 SEM image of KF/CP NPs[37]
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
KF/CP (NPs)
ZnO-NPs
45
H2O
68
H2O
75
CH3CN
65
CH3CN
78
CH3CN
80
Toluene
Toluene
Toluene
Solvent-free
Solvent-free
Solvent-free
H2O
56
68
70
80
90
FIGURE 2 XRD spectra of KF/CP NPs[37]
92
35
catalysts, KF/CP NPs is the best catalyst for these reactions.
KF/CP-NPs are a basic catalyst that can be prepared very
easily according to the reported article.[37] The morphology
of synthesized KF/CP-NPs was assessed by scanning elec-
tron microscopy images (SEM) as seen in Figure 1.
ZnO-NPs
H2O
47
ZnO-NPs
CH3CN
65
ZnO-NPs
Solvent-free
Solvent-free
Solvent-free
CH2Cl2
58
ZnO-NPs
75
ZnO-NPs
78
X-ray diffraction patterns (XRD) were used to calculate
the size of prepared KF/CP-NPs (Figure 2). The average
crystallite size (D) for KF/CP-NPs was calculated based on
the peak with the strongest intensity using Debye–Scherrer's
equation (D = Kλ/βcosθ), where D is the grain size, β is full
width at half-maximum or half width (FWHM) in radians,
h is the position of the maximum of diffraction peak, K is
the so-called shape factor (0.89), θ is Bragg's diffraction
angle, and λ is the X-ray wavelength used (1.5406 Aꢀ for
CuKα). Particle size of KF/CP has been found to be 41 nm.
The amount of catalyst is changed from 10 to 25%.
When the amount of catalyst is increased from 10 to 25%,
the yield of the reaction did not show any considerable
increase. Consequently, 10% (w/w) of KF/CP-NPs was
selected as the optimum amount. According to results, the
optimum conditions for the formation of compound 4a are
10 mol% KF/CP-NPs as a catalyst, 50ꢀC temperature, and
solvent-free conditions. These conditions are tested for other
reactions that are shown in Table 1.
TiO2-NPs
40
TiO2-NPs
H2O
75
TiO2-NPs
Toluene
CH3CN
68
TiO2-NPs
75
TiO2-NPs
Solvent-free
Solvent-free
H2O
80
TiO2-NPs
80
Fe3O4-MNPs
Fe3O4-MNPs
Fe3O4-MNPs
Fe3O4-MNPs
Fe3O4-MNPs
CuO-NPs
65
CH3CN
78
Toluene
Solvent-free
Solvent-free
H2O
75
82
85
30
CuO-NPs
CH3CN
48
CuO-NPs
Toluene
Solvent-free
Solvent-free
65
CuO-NPs
70
CuO-NPs
70
As shown in the Table 2, in the solvent-free conditions,
products have high yield than other solvents. For the CH3CN
and toluene, products have similar yield to solvent-free con-
ditions, but both solvents are organic and toxic. Of the
Reusability is one of the significant properties of this cat-
alyst. After the reaction was complete, ethyl acetate is
poured in the mixture of reactions, and the catalyst is

4
SHARIFI ET AL.
TABLE 3 Reuse of KF/CP-NPs for the synthesis of 4a
5. Intermediate 5 in the presence of KF/CP-NPs reacts with
compound 3 to produce intermediate 6 that undergoes cycli-
zation to generate chromene derivatives 4.
Cycle
1
2
3
4
5
Yield (%)
90
90
90
87
87
2.1 | Antioxidant evaluations
separated by filtration. The catalyst is then washed with
ethyl acetate, air-dried, and used directly under the same
conditions without further purification. It was shown that the
catalyst could be used for five runs without a considerable
decrease in the yield of product and its catalytic activity
(Table 3).
The structures of compounds 4a–p were confirmed by
1H NMR, 13C NMR, mass, and IR spectra, which are in
agreement with the proposed structures. For example, the 1H
NMR spectrum of 4e showed one singlet for methoxy pro-
tons at δ = 3.87 ppm and two doublet at 4.72 and 5.75 ppm
for methine proton, along with signals at 6.95–8.03 ppm for
aromatic moiety. In addition, one signal at δ = 162.3 ppm
was observed in the 13C NMR spectrum of 4e, which was
attributed to the carbonyl group. A proposed mechanism for
the creation of compound 4 is showed in Scheme 1. It is
conceivable that the reaction starts with the formation of
hydrogen bonding between the fluoride ion of KF/CP-NPs
as a basic catalyst and the proton of compound 1 and con-
densation with compounds 2, giving rise to the intermediate
2.1.1
| DPPH radical trapping activity
The DPPH radical trapping test is usually utilized to measure
the power of compounds to trap free radicals and their activ-
ity as an antioxidant in foods and biological systems.[38–40]
In this analysis, antioxidants, by giving hydrogen or an elec-
tron to the DPPH radical, generate the nonradical form of
DPPH that reduces the absorbance of DPPH at
517 nm.[38,41] Figure 3 shows the DPPH trapping activity of
4a-4d from 200 to 1,000 ppm concentrations compared to
synthetic antioxidants (BHT and TBHQ). The results dem-
onstrated that structure and concentration were effective fac-
tors for the DPPH scavenging activity (p < 0.05) (Figure 3).
In general, the power of free radical trapping activity of
4a-4d was attained TBHQ>BHT > 4c > 4b > 4a > 4d,
respectively that weak than to BHT and TBHQ. In all sam-
ples, free radical trapping activity was enhanced by increas-
ing the concentration so that the power of free radical
scavenging increased from 200 to 1,000 ppm concentrations.
For example, a concentration of 1,000 ppm of 4a had 12.3%
inhibition, while 200 ppm demonstrated 4.2% free radical
inhibition.
O
R
OH
R'
2.1.2
|
Ferric ions (Fe3+) reducing potential (FRAP)
R'''
O
R'
The reducing power of the prepared compounds was calcu-
lated by converting the amount of Fe3+/ferricyanide complex
to the Fe2+/ferrous form at 700 nm.[38] The power of reduc-
ing for compounds 4a–4d compared with synthetic antioxi-
dants (BHT and TBHQ) are shown in Figure 4. If one
compound has the bigger reducing power, this means a
higher absorbance of the compounds. The reducing activity
order of compounds 4a–4d was as follows: TBHQ>BHT >
4d > 4b > 4c > 4a (Figure 4). In all compounds, when
the concentration was enhanced, the power of ferric ions
reducing was increased. Compounds 4d and 4b displayed
KF/CP NPs
KF/CP NPs
R''
1
+
2 + 3
R''
R
R
O
O
6
5
O
R'
R''
R'''
KF/CP NPs
_
H2O
O
O
4
SCHEME 1 Green synthetic of pyrimido [2,1-a] isoquinolines
FIGURE 3 Radical scavenging activity (RSA) of compounds 4a–4d.
Values in the same concentration followed by different letters are
significantly different (p < 0.05)
FIGURE 4 Ferric ions (Fe3+) reducing antioxidant power (FRAP) of
compounds 4a–4d. Values in the same concentration followed by different
letters are significantly different (p < 0.05)

SHARIFI ET AL.
5
very good reducing activity compared to the standards (BHT
and TBHQ). In addition, 4c and 4a had medium reducing
activity than BHT and TBHQ. The power of these com-
pounds in reducing is an indicator of their electron transfer.
oven for 30 hr. The resulting material was powdered using a
pestle and mortar. The obtained KF/CP-NPs retained in a
desiccator until required.
4.2 | General procedure for the synthesis of chromene
derivatives 4
3
| CONCLUSION
For example, to a stirred mixture of acetophenone 2b
(2 mmol) and 4-methyl benzaldehyde 3b (2 mmol) in the
presence of catalytic amounts of KF/CPNPs (10 mol%)
under solvent-free conditions and 50ꢀC was added
4-hydroxycumarine 1 (2 mmol) after 10 min. The reaction
mixture was stirred for 10 min. After completion of the reac-
tion (monitored by TLC), 15 mL H2O was poured in the
mixture of reactions. The reaction mixture was filtered, and
the solid residue was washed by ethyl acetate to remove the
catalyst. By evaporating solvent compounds, 4b was sepa-
rated. These compounds are purified by Et2O.
In conclusion, the main purpose of carrying out this work
was to investigate a new method for the synthesis of chro-
mene derivatives via three-component reaction of
4-hydroxycumarine, aldehydes or ketones, and methyl
ketones under solvent-free conditions at 50ꢀC. The main
advantage of this procedure compared to some previously
reported approaches was using environment-friendly synthe-
sized KF/CP nanoparticles. The method offers other advan-
tages, including high yields of products and easy
experimental work-up procedure. In this research, antioxi-
dant activity was investigated for some synthesized com-
pounds, such as 4a–4d, using the DPPH radical trapping and
reducing potential tests of ferric ion and comparing results
with synthetic antioxidants (TBHQ and BHT). In this study,
compounds 4a–4d demonstrated moderate DPPH radical
trapping and good reducing power of ferric ion
2,4-Diphenylpyrano[3,2-c]chromen-5(4H)-one (4a):
Pale yellow powder; mp 172–174ꢀC, yield: 0.63 g (90%). IR
(KBr) (νmax/cm−1): 1720, 1,695, 1,587, 1,457, 1,328,
1
1,129 cm−1. H NMR (500 MHz, CDCl3) δ 4.52 (1H, d,
3
3JHH = 4.2 Hz, CH), 5.78 (1 H, d, JHH = 4.3 Hz, CH),
7.08 (2 H, t, 3JHH = 7.5 Hz, 2 CH), 7.16 (2 H, t, 3JHH = 7.6
3
Hz, 2 CH), 7.23 (1 H, t, JHH = 7.6 Hz, CH), 7.35 (1 H, d,
3JHH = 7.6 Hz, CH), 7.42 (1 H, t, 3JHH = 7.5 Hz, CH), 7.47
3
3
(1 H, t, JHH = 7.5 Hz, CH), 7.52 (1 H, t, JHH = 7.7 Hz,
4
| EXPERIMENTAL
3
CH), 7.58 (2 H, d, JHH = 7.7 Hz, 2 CH), 7.72 (2 H, d,
3JHH = 7.6 Hz, 2 CH), 8.04 (1 H, d, JHH = 7.7 Hz, CH)
3
All chemicals in this work were prepared in Fluka (Buchs,
Switzerland) and were utilized without further purification.
Clinoptilolite was obtained from the Afrandtooska Company
in the region of Semnan. KF/CP-NPs were prepared accord-
ing to literature reported.[37] Melting points were measured
on an electrothermal 9,100 apparatus. Elemental analyses
for C, H, and N were carried out using a Heraeus CHN–O-
ppm. 13C NMR (125 MHz, CDCl3) δ 37.2 (CH), 103.6
(CH), 104.0 (C), 115.2 (C), 116.5 (CH), 123.2 (CH), 124.8
(CH), 125.2 (CH), 127.4 (2 CH), 128.6 (2CH), 129.2 (2CH),
129.6 (2CH), 130.2 (CH), 132.3 (CH), 132.9 (C), 143.5 (C),
146.8 (C), 153.2 (C), 156.2 (C), 161.5 (C=O) ppm. Anal.
calcd for C24H16O3: C, 81.80; H, 4.58. Found: C, 81.65; H,
4.43. MS, m/z (%): 352 (M+, 15), 275 (68), 144 (56),
77 (100).
Rapid analyzer. Mass spectra were recorded on
a
FINNIGAN-MAT 8430 spectrometer operating at an ioniza-
tion potential of 70 eV. IR spectra were measured on a Shi-
2-Phenyl-4-p-tolylpyrano[3,2-c]chromen-5(4H)-one (4b):
white powder; mp 183–185ꢀC, yield: 0.64 g (87%). IR
(KBr) (νmax/cm−1): 1725, 1,689, 1,568, 1,487, 1,356, 1,295,
1,137 cm−1. 1H NMR (500 MHz, CDCl3) δ 2.28 (3H, s, Me),
4.62 (1 H, d, 3JHH = 4.8 Hz, CH), 5.78 (1 H, d, 3JHH = 4.8 Hz,
1
madzu IR-460 spectrometer. H and 13C NMR spectra were
measured with a BRUKER DRX-500 AVANCE spectrome-
ter at 500.1 and 125.8 MHz, respectively. 1H and 13C spectra
were obtained for solutions in CDCl3 using TMS as internal
standard or 85% H3PO4 as external standard.
CH), 7.05 (2 H, d, 3JHH = 7.6 Hz, 2 CH), 7.12 (2 H, t, 3JHH
=
7.6 Hz, 2 CH), 7.32 (1 H, t, 3JHH = 7.7 Hz, CH), 7.41 (1 H, d,
3
3JHH = 7.5 Hz, CH), 7.45 (1 H, t, JHH = 7.6 Hz, CH), 7.48
4.1 | Preparation of nano-KF/clinoptilolite
3
3
(1 H, t, JHH = 7.6 Hz, CH), 7.52 (2 H, d, JHH = 7.6 Hz,
3
Nano-sized natural clinoptilolite zeolite was generated by
grinding in a planetary ball mill using a zirconia vial set in
dry conditions with a time period of about 20 min. Then, the
KF/CP-NPs catalyst was prepared according to previously
reported procedure.[37] Thus, 1 g of KF was dissolved in dis-
tilled water (10 mL) and nanoclinoptilolite (9 g). The mix-
ture was stirred for 50 min. Then, the water was evaporated
at 60–70ꢀC under reduced pressure. Moreover, the impreg-
nated clinoptilolite was dried at 70–80ꢀC in a vacuum drying
2 CH), 7.62 (2 H, d, JHH = 7.6 Hz, 2 CH), 7.76 (1 H, d,
3JHH = 7.6 Hz, CH) ppm. 13C NMR (125 MHz, CDCl3) δ
23.4 (Me), 43.2 (CH), 103.5 (CH), 104.2 (C), 116.3 (C), 116.7
(CH), 123.4 (CH), 125.2 (CH), 127.2 (2 CH), 128.4 (2 CH),
129.2 (2CH), 129.6 (2CH), 130.4 (CH), 132.3 (CH), 133.2 (C),
138.2 (C), 139.7 (C), 149.3 (C), 155.4 (C), 156.4 (C), 161.7
(C=O) ppm. MS, m/z (%): 366 (M+, 20), 351 (52), 275 (100).
Anal. calcd for C25H18O3: C, 81.95; H, 4.95. Found: C,
81.72; H, 4.83.

6
SHARIFI ET AL.
4-(Benzo[d][1,3]dioxol-5-yl)-2-phenylpyrano[3,2-c]
127.9 (CH), 128.3 (2CH), 128.7 (2CH), 129.6 (2 CH), 132.5
(CH), 142.3 (C), 149.5 (C), 155.2 (C), 156.3 (C), 159.7(C),
162.2 (C=O) ppm. MS, m/z (%): 382 (M+, 15), 289 (93),
31 (100). Anal. calcd for C25H18O4: C, 78.52; H, 4.74.
Found: C, 78.67; H, 4.86.
2-(4-Bromophenyl)-4-phenylpyrano[3,2-c]chromen-5
(4H)-one (4f): White powder; mp 198–200ꢀC, yield:
0.65 g (75%). IR (KBr) (νmax/cm−1): 1725, 1,689, 1,568,
chromen-5(4H)-one (4c): White powder; mp 175–177ꢀC,
yield: 0.75 g (95%). IR (KBr) (νmax/cm−1): 1727, 1,693,
1,587, 1,468, 1,378, 1,295, 1,129 cm−1
.
1H NMR
3
(500 MHz, CDCl3) δ 4.73 (1 H, d, JHH = 5.2 Hz, CH),
3
3
5.68 (1 H, d, JHH = 5.2 Hz, CH), 5.87 (1 H, d, JHH
=
1.6 Hz, CH), 5.92 (1 H, d, 3JHH = 1.6 Hz, CH), 6.82 (1 H,
d, 3JHH = 7.6 Hz, CH), 6.95 (1 H, d, 3JHH = 7.6 Hz, CH),
1,456, 1,386, 1,295, 1,137 cm−1
.
1H NMR (500 MHz,
3
7.12 (2 H, t, JHH = 7.5 Hz, 2 CH), 7.18 (1 H, s, CH),
3
3
3
CDCl3) δ 4.83 (1 H, d, JHH = 5.8 Hz, CH), 5.92 (1 H, d,
7.37 (1 H, t, JHH = 7.6 Hz, CH), 7.42 (1 H, d, JHH
=
3JHH = 5.8 Hz, CH), 7.15 (2 H, t, JHH = 7.6 Hz, 2 CH),
3
3
7.6 Hz, CH), 7.48 (1 H, t, JHH = 7.5 Hz, CH), 7.53 (1 H,
3
3
3
3
7.25 (1 H, t, JHH = 7.6 Hz, CH), 7.36 (1 H, t, JHH = 7.5
t, JHH = 7.6 Hz, CH), 7.63 (2 H, d, JHH = 7.6 Hz,
3
3
2 CH), 7.75 (1 H, d, JHH = 7.6 Hz, CH) ppm. 13C NMR
Hz, CH), 7.42 (1 H, d, JHH = 7.6 Hz, CH), 7.46 (1 H, t,
3JHH = 7.6 Hz, CH), 7.52 (2 H, d, JHH = 7.6 Hz, 2 CH),
3
(125 MHz, CDCl3) δ 48.3 (CH), 101.2 (CH2), 103.7
(CH), 104.3 (C), 109.5 (CH), 110.3 (CH), 116.5 (C),
116.8 (CH), 122.3 (CH), 124.5 (CH), 125.3 (CH), 128.2
(2 CH), 128.9 (2CH), 130.2 (CH), 132.3 (CH), 133.4 (C),
135.3 (C), 147.2 (C), 149.3 (C), 150.6 (C), 155.6 (C),
156.5 (C), 161.3 (C=O) ppm. MS, m/z (%): 396 (M+, 15),
275 (100), 189 (68). Anal. calcd for C25H16O5: C,
75.75; H, 4.07. Found: C, 75.87; H, 4.23.
3
3
7.56 (2 H, d, JHH = 7.6 Hz, 2 CH), 7.65 (2 H, d, JHH
=
C
7.6 Hz, 2 CH), 7.84 (1 H, d, 3JHH = 7.6 Hz, CH) ppm. 13
NMR (125 MHz, CDCl3) δ 48.4 (CH), 103.7 (CH), 104.6
(C), 116.7 (C), 116.9 (CH), 123.6 (C), 124.2 (CH), 125.3
(CH), 127.4 (CH), 128.5 (2CH), 128.9 (2CH), 129.3
(2 CH), 131.8 (2 CH), 132.2 (CH), 132.5 (C), 142.3 (C),
149.8 (C), 155.4 (C), 156.5 (C), 161.4 (C=O) ppm. MS,
m/z (%): 431 (M+, 15), 156 (100), 77 (68). Anal. calcd for
C24H15BrO3: C, 66.84; H, 3.51. Found: C, 66.96; H, 3.63.
2,4-Bis(4-chlorophenyl)pyrano[3,2-c]chromen-5(4H)-
one (4g): Pale yellow powder; mp 236–238ꢀC, yield: 0.82 g
(98%). IR (KBr) (νmax/cm−1): 1727, 1,695, 1,578, 1,468,
4-(4-Nitrophenyl)-2-phenylpyrano[3,2-c]chromen-5
(4H)-one (4d): Yellow powder; mp 227–229ꢀC, yield:
0.73 g (92%). IR (KBr) (νmax/cm−1): 1726, 1,695, 1,596,
1,485, 1,378, 1,284, 1,135 cm−1
.
1H NMR (500 MHz,
3
CDCl3) δ 4.68 (1 H, d, JHH = 4.5 Hz, CH), 5.83 (1 H, d,
3
1
3JHH = 4.5 Hz, CH), 7.07 (2 H, t, JHH = 7.6 Hz, 2 CH),
1,392, 1,278, 1,153 cm−1. H NMR (500 MHz, CDCl3) δ
3
3
7.35 (1 H, t, 3JHH = 7.6 Hz, CH), 7.42 (1 H, t, 3JHH = 7.5
5.02 (1 H, d, JHH = 4.6 Hz, CH), 5.87 (1 H, d, JHH = 4.6
Hz, CH), 7.48 (1 H, d, JHH = 7.5 Hz, CH), 7.52 (1 H, t,
Hz, CH), 7.16 (2 H, d, 3JHH = 7.6 Hz, 2 CH), 7.22 (2 H, d,
3
3
3
3JHH = 7.5 Hz, CH), 7.58 (2 H, d, JHH = 7.6 Hz, 2 CH),
3JHH = 7.7 Hz, 2 CH), 7.37 (1 H, t, JHH = 7.5 Hz, CH),
3
3
3
3
7.68 (2 H, d, JHH = 7.8 Hz, 2 CH), 7.76 (1 H, d, JHH
=
7.43 (1 H, d, JHH = 7.6 Hz, CH), 7.48 (1 H, t, JHH = 7.6
Hz, CH), 7.56 (2 H, d, 3JHH = 7.6 Hz, 2 CH), 7.65 (2 H, d,
3
7.6 Hz, CH), 7.87 (2 H, d, JHH = 7.8 Hz, 2 CH) ppm.
13C NMR (125 MHz, CDCl3) δ 46.8 (CH), 103.6 (CH),
104.3 (C), 116.5 (C), 117.2 (CH), 123.9 (2 CH), 124.3
(CH), 125.5 (CH), 128.5 (2 CH), 129.3 (2CH), 129.8
(2CH), 130.6 (CH), 132.5 (CH), 133.4 (C), 147.2 (C),
148.5 (C), 149.2 (C), 155.4 (C), 156.5 (C), 161.8 (C=O)
ppm. MS, m/z (%): 397 (M+, 10), 350 (45), 275 (100).
Anal. calcd for C24H15NO5: C, 72.54; H, 3.80. Found: C,
72.76; H, 3.94.
3JHH = 7.6 Hz, 2 CH), 7.78 (1 H, d, JHH = 7.6 Hz, CH)
3
ppm. 13C NMR (125 MHz, CDCl3) δ 48.3 (CH), 104.2
(CH), 104.8 (C), 116.3 (C), 116.5 (CH), 124.2 (CH), 125.6
(CH), 128.6 (2 CH), 129.2 (2 CH), 130.2 (2CH), 132.3
(CH), 132.6 (C), 132.8 (C), 134.3 (C), 140.2 (C), 149.2 (C),
155.4 (C), 156.7 (C), 161.2 (C=O) ppm. MS, m/z (%):
421 (M+, 10), 310 (58), 111 (100), 77 (64). Anal. calcd for
C24H14Cl2O3: C, 68.43; H, 3.35. Found: C, 68.62; H, 3.49.
4-(4-Chlorophenyl)-2-p-tolylpyrano[3,2-c]chromen-5
(4H)-one (4h): Pale yellow powder; mp 223–225ꢀC, yield:
0.76 g (95%). IR (KBr) (νmax/cm−1): 1725, 1,687, 1,564,
4-(4-methoxyphenyl)-2-phenylpyrano[3,2-c]chromen-
5(4H)-one (4e): Pale yellow powder; mp 157–159ꢀC, yield:
0.51 g (70%). IR (KBr) (νmax/cm−1): 1727, 1,690, 1,582,
1,487, 1,375, 1,283, 1,129 cm−1
.
1H NMR (500 MHz,
1,476, 1,387, 1,297, 1,164 cm−1
.
1H NMR (500 MHz,
3
3
CDCl3) δ 3.87 (3H, s, Me), 4.65 (1 H, d, JHH = 5.6 Hz,
CDCl3) δ 2.35 (3 H, s, Me), 5.06 (1 H, d, JHH = 4.8 Hz,
CH), 5.83 (1 H, d, 3JHH = 5.6 Hz, CH), 7.12 (2 H, t, 3JHH
=
CH), 5.93 (1 H, d, JHH = 4.8 Hz, CH), 7.15 (2 H, d,
3
7.6 Hz, 2 CH), 7.23 (1 H, t, JHH = 7.6 Hz, CH), 7.34
(2 H, d, 3JHH = 7.6 Hz, 2 CH), 7.38 (1 H, t, 3JHH = 7.6 Hz,
3JHH = 7.5 Hz, 2 CH), 7.25 (2 H, d, JHH = 7.5 Hz, 2 CH),
3
3
3
3
7.35 (1 H, t, JHH = 7.6 Hz, CH), 7.39 (2 H, d, JHH = 7.6
3
3
CH), 7.42 (1 H, d, JHH = 7.6 Hz, CH), 7.48 (2 H, d,
Hz, 2 CH),7.44 (1 H, d, JHH = 7.5 Hz, CH), 7.52 (1 H, t,
3
3
3JHH = 7.6 Hz, 2 CH), 7.54 (1 H, t, JHH = 7.6 Hz, CH),
3JHH = 7.6 Hz, CH), 7.64 (2 H, d, JHH = 7.6 Hz, 2 CH),
3
3
3
7.62 (2 H, d, JHH = 7.6 Hz, 2 CH), 7.78 (1 H, d, JHH
=
7.75 (1 H, d, JHH = 7.6 Hz, CH) ppm. 13C NMR
7.6 Hz, CH) ppm. 13C NMR (125 MHz, CDCl3) δ 48.2
(CH), 55.6 (MeO), 103.6 (CH), 104.5 (C), 114.3 (2 CH),
116.5 (C), 116.8 (CH), 124.3 (CH), 125.5 (CH), 127.4 (C),
(125 MHz, CDCl3) δ 21.4 (Me), 48.5 (CH), 104.3 (CH),
105.2 (C), 116.4 (C), 116.7 (CH), 124.3 (CH), 125.7 (CH),
126.2 (2 CH), 128.8 (2 CH), 129.3 (2CH), 129.7 (2 CH),

SHARIFI ET AL.
7
131.8 (C), 132.2 (CH), 132.6 (C), 136.7 (C), 140.2 (C),
150.3 (C), 155.4 (C), 156.7 (C), 161.3 (C=O) ppm. MS, m/z
(%): 400 (M+, 10), 365 (68), 91 (100), 77 (68). Anal. calcd
for C25H17ClO3: C, 74.91; H, 4.27. Found: C,
74.75; H, 4.16.
calcd for C25H18O3: C, 81.95; H, 4.95. Found: C, 81.83; H,
4.82. MS, m/z (%): 366 (M+, 15), 296 (84), 77 (100).
9-Methyl-2-phenyl-4-p-tolylpyrano[3,2-c]chromen-5
(4H)-one (4l): white powder; mp 209–211ꢀC, yield: 0.69 g
(90%). IR (KBr) (νmax/cm−1): 1726, 1,695, 1,587, 1,483,
1
4-Methyl-2,4-diphenylpyrano[3,2-c]chromen-5(4H)-
one (4i): white powder; mp 181–182ꢀC, yield: 0.62 g
(85%). IR (KBr) (νmax/cm−1): 1726, 1,695, 1,578, 1,475,
1,376, 1,285, 1,197 cm−1. H NMR (500 MHz, CDCl3) δ
2.26 (3H, s, Me), 2.35 (3 H, s, Me), 4.78 (1 H, d, 3JHH = 5.3
3
Hz, CH), 5.62 (1 H, d, JHH = 5.3 Hz, CH), 7.04 (2 H, d,
1
3
1,386, 1,284, 1,165 cm−1. H NMR (500 MHz, CDCl3) δ
3JHH = 7.6 Hz, 2 CH), 7.09 (2 H, t, JHH = 7.6 Hz, 2 CH),
1.65 (3 H, s, Me), 6.22 (1 H, s, CH), 7.15 (2 H, t, 3JHH = 7.6
7.16 (2 H, d, JHH = 7.5 Hz, CH), 7.22 (1 H, d, JHH = 7.5
3
3
3
3
Hz, 2 CH), 7.23 (1 H, t, JHH = 7.6 Hz, CH), 7.28 (2 H, t,
Hz, CH), 7.42 (1 H, t, JHH = 7.6 Hz, CH), 7.47 (1 H, s,
3
3
3JHH = 7.6 Hz, 2 CH), 7.35 (1 H, t, JHH = 7.5 Hz, CH),
CH), 7.53 (2 H, d, JHH = 7.6 Hz, 2 CH), 7.64 (2 H, d,
7.39 (2 H, d, 3JHH = 7.6 Hz, 2 CH), 7.45 (1 H, t, 3JHH = 7.5
3JHH = 7.6 Hz, 2 CH), 7.76 (1 H, d, JHH = 7.6 Hz, CH)
3
3
Hz, CH), 7.52 (1 H, d, JHH = 7.5 Hz, CH), 7.58 (1 H, t,
ppm. 13C NMR (125 MHz, CDCl3) δ 21.3 (Me), 22.5 (Me),
47.8 (CH), 103.8 (CH), 104.3 (C), 116.4 (C), 120.4 (CH),
126.2 (CH), 127.2 (2 CH), 128.3 (2 CH), 128.8 (2 CH),
129.3 (2CH), 130.5 (CH), 133.6 (C), 133.8 (CH), 134.2 (C),
138.3 (C), 139.2 (C), 149.5 (C), 150.7 (C), 157.2 (C), 162.3
(C=O) ppm. MS, m/z (%): 380 (M+, 10), 365 (65),
303 (28), 289 (100). Anal. calcd for C26H20O3: C, 82.08; H,
5.30. Found: C, 82.27; H, 5.42.
3
3JHH = 7.6 Hz, CH), 7.63 (2 H, d, JHH = 7.6 Hz, 2 CH),
3
7.75 (1 H, d, JHH = 7.6 Hz, CH) ppm. 13C NMR
(125 MHz, CDCl3) δ 28.3 (Me), 51.3 (C), 107.5 (C), 108.6
(CH), 116.4 (CH), 124.3 (CH), 125.6 (CH), 127.2 (CH),
128.2 (2 CH), 129.4 (2CH), 129.8 (2CH), 130.2 (2CH),
130.8 (CH), 132.2 (CH), 133.4 (C), 142.3 (C), 149.3 (C),
155.3 (C), 156.3 (C), 161.2 (C=O) ppm. MS, m/z (%):
366 (M+, 15), 296 (86), 77 (100). Anal. calcd for
C25H18O3: C, 81.95; H, 4.95. Found: C, 81.78; H, 4.76.
2-Methyl-4-phenylpyrano[3,2-c]chromen-5(4H)-one (4j):
pale yellow powder; mp 134–136ꢀC, yield: 0.62 g (90%). IR
(KBr) (νmax/cm−1): 1728, 1,698, 1,594, 1,489, 1,387, 1,289,
1,158 cm−1. 1H NMR (500 MHz, CDCl3) δ 1.87 (3 H, s, Me),
4.86 (1 H, d, 3JHH = 4.6 Hz, CH), 5.85 (1 H, d, 3JHH = 4.6 Hz,
2-(4-bromophenyl)-4-(4-methoxyphenyl)pyrano[3,2-c]
chromen-5(4H)-one (4m): Pale yellow powder; mp
156–158ꢀC, yield: 0.80 g (87%). IR (KBr) (νmax/cm−1):
1728, 1,692, 1,578, 1,483, 1,395, 1,294, 1,176 cm−1 1H
.
NMR (500 MHz, CDCl3) δ 3.87 (3 H, s, MeO), 4.85 (1 H,
3
3
d, JHH = 5.3 Hz, CH), 5.74 (1 H, d, JHH = 5.3 Hz, CH),
3
3
6.94 (1 H, d, JHH = 7.6 Hz, CH), 7.18 (1 H, t, JHH = 7.6
CH), 7.13 (2 H, t, 3JHH = 7.6 Hz, 2 CH), 7.25 (1 H, t, 3JHH
=
Hz, CH), 7.22 (1 H, s, CH), 7.32 (1 H, d, JHH = 7.6 Hz,
3
3
3
7.6 Hz, CH), 7.36 (1 H, t, JHH = 7.6 Hz, CH), 7.42 (1 H, d,
CH),7.37 (1 H, t, JHH = 7.5 Hz, CH), 7.42 (1 H, d, 3JHH
=
3
3JHH = 7.6 Hz, CH), 7.49 (1 H, t, JHH = 7.6 Hz, CH), 7.56
7.6 Hz, CH), 7.48 (1 H, t, 3JHH = 7.6 Hz, CH), 7.54 (2 H, d,
3
3
3
(2 H, d, JHH = 7.6 Hz, 2 CH), 7.68 (1 H, d, JHH = 7.6 Hz,
CH) ppm. 13C NMR (125 MHz, CDCl3) δ 19.2 (Me), 46.7 (C),
100.3 (CH), 103.5 (C), 116.5 (C), 117.4 (CH), 124.2 (CH),
125.3 (CH), 127.2 (CH), 128.2 (2CH), 129.5 (2CH), 131.8
(CH), 141.3 (C), 148.2 (C), 156.2 (C), 157.4 (C), 161.5 (C=O)
ppm. Anal. calcd for C19H14O3: C, 78.61; H, 4.86. Found: C,
78.76; H, 4.98. MS, m/z (%): 290 (M+, 10), 213 (86), 77 (100).
9-Methyl-2,4-diphenylpyrano[3,2-c]chromen-5(4H)-
one (4k): white powder; mp 217–219ꢀC, yield: 0.69 g
(95%). IR (KBr) (νmax/cm−1): 1732, 1,697, 1,586, 1,476,
3JHH = 7.6 Hz, 2 CH), 7.62 (2 H, d, JHH = 7.6 Hz, 2 CH),
7.75 (1 H, d, JHH = 7.6 Hz, CH) ppm. 13C NMR
3
(125 MHz, CDCl3) δ 49.5 (Me), 55.6 (MeO), 103.8 (CH),
104.6 (C), 115.3 (CH), 116.3 (C), 116.8 (CH), 118.6 (CH),
121.3 (CH), 122.4 (CH), 123.2 (C), 124.3 (CH), 125.5 (CH),
128.8 (2 CH), 131.5 (2 CH), 132.2 (CH), 132.8 (C), 144.2
(C), 149.3 (C), 155.2 (C), 156.2 (C), 159.3 (C), 162.2 (C=O)
ppm. MS, m/z (%): 461 (M+, 10), 156 (100), 77 (82). Anal.
calcd for C25H17BrO4: C, 65.09; H, 3.71. Found: C,
65.23; H, 3.85.
1
1,358, 1,292, 1,162 cm−1. H NMR (500 MHz, CDCl3) δ
2-(4-bromophenyl)-4-(4-ethoxyphenyl)pyrano[3,2-c]
chromen-5(4H)-one (4n): Pale yellow powder; mp
154–156ꢀC, yield: 0.86 g (90%). IR (KBr) (νmax/cm−1):
1725, 1,695, 1,583, 1,487, 1,368, 1,257, 1,184 cm−1. 1H
3
2.36 (3 H, s, Me), 4.94 (1H, d, JHH = 4.8 Hz, CH), 5.83
3
3
(1 H, d, JHH = 4.8 Hz, CH), 7.05 (2 H, t, JHH = 7.6 Hz,
3
2 CH), 7.15 (1 H, d, JHH = 7.6 Hz, CH), 7.23 (2 H, t,
3JHH = 7.6 Hz, 2 CH), 7.29 (1 H, d, JHH = 7.6 Hz, CH),
NMR (500 MHz, CDCl3) δ 1.38 (3 H, t, JHH = 7.3 Hz,
3
3
3
3
3
7.32 (1 H, t, JHH = 7.6 Hz, CH), 7.39 (1 H, t, JHH = 7.5
Me), 4.23 (2 H, q, JHH = 7.3 Hz, CH2O), 4.67 (1 H, d,
3
Hz, CH), 7.45 (1 H, s, CH), 7.53 (2 H, d, JHH = 7.6 Hz,
3JHH = 4.8 Hz, CH), 5.84 (1 H, d, 3JHH = 4.8 Hz, CH), 6.95
(2 H, d, 3JHH = 7.6 Hz, 2 CH), 7.15 (2 H, d, 3JHH = 7.5 Hz,
2 CH), 7.63 (2 H, d, JHH = 7.6 Hz, 2 CH) ppm. 13C NMR
3
3
(125 MHz, CDCl3) δ 22.3 (Me), 48.6 (C), 104.2 (CH),
104.6 (C), 116.5 (C), 120.3 (CH), 126.3 (CH), 127.4 (CH),
128.3 (2 CH), 128.8 (2 CH), 129.2 (2 CH), 129.8 (2 CH),
130.4 (CH), 133.6 (C), 134.2 (CH), 134.2 (C), 142.3 (C),
150.2 (C), 151.2 (C), 157.3 (C), 162.4 (C=O) ppm. Anal.
2 CH), 7.37 (1 H, t, JHH = 7.5 Hz, CH),7.42 (1 H, d,
3JHH = 7.6 Hz, CH), 7.54 (1 H, t, 3JHH = 7.6 Hz, CH), 7.59
(2 H, d, 3JHH = 7.6 Hz, 2 CH), 7.64 (2 H, d, 3JHH = 7.6 Hz,
3
2 CH), 7.75 (1 H, d, JHH = 7.6 Hz, CH) ppm. 13C NMR
(125 MHz, CDCl3) δ 14.2 (Me), 18.6 (CH), 63.2 (CH2O),

8
SHARIFI ET AL.
103.6 (CH), 104.2 (C), 115.6 (2 CH), 116.4 (C), 117.2 (CH),
123.2 (C), 124.3 (CH), 125.6 (CH), 129.2 (2 CH), 130.4
(2 CH), 131.4 (2 CH), 131.8 (CH), 132.6 (C), 133.5 (C),
149.8 (C), 155.3 (C), 156.4 (C), 159.5 (C), 162.4 (C=O)
ppm. MS, m/z (%): 475 (M+, 10), 430 (86), 77 (82),
45 (100). Anal. calcd for C26H19BrO4: C, 65.70; H, 4.03.
Found: C, 65.84; H, 4.18.
temperature. Compounds 4a-4d were replaced with 3 mL
methanol in the control sample. Butylated hydroxytoluene
(BHT) and 2-tert-butylhydroquinone (TBHQ) were used as
standard controls. The DPPH operation is computed using
the following formula:43
I = [(AB-AS)/AB] × 100
2,4-dimethyl-4-phenylpyrano[3,2-c]chromen-5(4H)-
one (4o): white powder; mp 143–145ꢀC, yield: 0.49 g
(78%). IR (KBr) (νmax/cm−1): 1726, 1,692, 1,586, 1,487,
where I = DPPH inhibition (%), AB = absorbance of con-
trol sample (0 min), and AS = absorbance of an examined
sample at the end of the reaction (after 30 min).
1
1,378, 1,282, 1,173 cm−1. H NMR (500 MHz, CDCl3) δ
3
1.38 (3 H, t, JHH = 7.3 Hz, Me), 1.68 (3 H, s, Me), 2.23
3
(2 H, m, CH2), 5.36 (1 H, s, CH), 7.16 (1 H, t, JHH = 7.5
4.4 | Reducing power experiment
3
Hz, CH), 7.25 (2 H, t, JHH = 7.6 Hz, 2 CH), 7.32 (2 H, d,
The power of 4a-4d to reduce iron (III) was guessed using
the Yildirim et al.[42] procedure. The compounds 4a-4d
(1 mL) were mixed with 2.5 mL of phosphate buffer (0.2 M,
pH 6.6) and 2.5 mL of potassium ferricyanide (K3Fe[CN]6;
10 g/L) and stirred for 30 min at 50ꢀC. After that, 2.5 mL of
trichloroacetic acid (10% w/v) was added to the solution and
centrifuged for 10 min. Finally, 2.5 mL of the supernatant
was combined with 2.5 mL of distilled water and 0.5 mL
FeCl3 (1 g/L). The absorbance of samples was calculated at
700 nm. Higher absorbance means were attributed to higher
reducing power.
3
3JHH = 7.5 Hz, 2 CH), 7.37 (1 H, t, JHH = 7.6 Hz, CH),
3
3
7.42 (1 H, d, JHH = 7.6 Hz, CH), 7.48 (1 H, t, JHH = 7.5
Hz, CH), 7.63 (1 H, d, 3JHH = 7.5 Hz, CH) ppm. 13C NMR
(125 MHz, CDCl3) δ 11.2 (Me), 28.2 (Me), 31.4 (Me), 43.5
(C), 101.2 (C), 115.4 (C), 116.2 (CH), 119.3 (CH), 123.2
(CH), 124.5 (CH), 126.7 (2 CH), 127.2 (CH), 129.7 (2 CH),
132.2 (CH), 141.6 (C), 153.3 (C), 155.5 (C), 156.2 (C),
160.8 (C=O) ppm. MS, m/z (%): 318 (M+, 10), 241 (86),
77 (100). Anal. calcd for C21H18O3: C, 79.22; H, 5.70.
Found: C, 79.37; H, 5.86.
4-(4-methoxyphenyl)-2-tert-butylpyrano[3,2-c]chro-
men-5(4H)-one (4p): Pale brown powder; mp 162–164ꢀC,
yield: 0.56 g (78%). IR (KBr) (νmax/cm−1): 1725, 1,693,
4.4.1
| Statistical study
Each measurement was performed thrice. The data were ana-
lyzed by running one way analysis of variance (ANOVA)
utilizing SPSS software version 18.0. A one-way ANOVA
was used to evaluate difference in the mean value of samples
and control. All mean separations were performed using
Duncan multiple range examination, with an importance
level of 95% (p < 0.05).
1,585, 1,476, 1,378, 1,289, 1,134 cm−1
.
1H NMR
(500 MHz, CDCl3) δ 1.26 (9H, s, Me3C), 3.75 (3 H, s,
3
MeO), 4.73 (1 H, d, JHH = 5.4 Hz, CH), 5.76 (1 H, d,
3
3JHH = 5.4 Hz, CH), 6.94 (2 H, d, JHH = 7.7 Hz, 2 CH),
3
3
7.12 (2 H, d, JHH = 7.7 Hz, 2 CH), 7.34 (2 H, d, JHH
=
7.6 Hz, 2 CH), 7.38 (1 H, t, 3JHH = 7.6 Hz, CH), 7.42 (1 H,
3
3
d, JHH = 7.6 Hz, CH), 7.54 (1 H, t, JHH = 7.6 Hz, CH),
7.76 (1 H, d, JHH = 7.6 Hz, CH) ppm. 13C NMR
3
(125 MHz, CDCl3) δ 31.2 (Me3C), 34.2 (Me3C), 35.6 (CH),
55.6 (MeO), 95.4 (CH), 101.3 (C), 114.6 (2 CH), 115.4 (C),
117.5 (CH), 125.2 (CH), 126.4 (CH), 127.5 (2 CH), 128.6
(C), 132.2 (CH), 155.2 (C), 156.3 (C), 158.2 (C), 159.6 (C),
163.4 (C=O) ppm. MS, m/z (%): 362 (M+, 10), 305 (84),
57 (100), Anal. calcd for C23H22O4: C, 76.22; H, 6.12.
Found: C, 76.34; H, 6.25.
ACKNOWLEDGMENTS
We are grateful to the University of Sistan & Baluchestan
Research Council for financial support of this work.
ORCID
Samanehsadat Sharifi https://orcid.org/0000-0002-9743-
7238
4.3 | DPPH radical scavenging test
Some derivatives of synthesized chromene derivatives, such
as 4a–4d, are tested as antioxidants. Antioxidant activity of
this compounds was measured by the DPPH (2, 2-Diphenyl-
1-picrylhydrazyl) radical trapping test, consistent with the
method reported by Shimada et al.[41] Different concentra-
tions of 4a–4d (200–1,000 ppm) were added to an identical
volume of methanolic solution of DPPH (1 mM). The mix-
tures were combined and then placed in a dark room. After
30 min, absorbance of the mixture was measured. The maxi-
mum absorbance of the mixture was 517 nm at room
REFERENCES
[1] A. Domling, Chem. Rev. 2006, 106, 17.
[2] I. Ugi, Adv. Synth. Catal. 1997, 339, 499.
[3] N. K. Terrett, M. Gardner, D. W. Gordon, R. J. Kobylecki, J. Steele, Tetra-
hedron 1995, 51, 8135.
[4] A. Domling, I. Ugi, Multicomponent reactions with isocyanides. Angew.
Chem. 2000, 39, 3168.
[5] K. Tanaka, F. Toda, Chem. Rev. 2000, 100, 1025.
[6] F. Shirini, K. Marjani, H. T. Nahzomi, ARKIVOC 2007, 51.
[7] G. Thirunarayanan, G. Vanangamudi, ARKIVOC 2006, 58.
[8] (a) A. Deiters, S. F. Martin, Chem. Rev. 2004, 104, 2199. (b) X. F. Wu,
H. Neumann, M. Beller, Chem. Rev. 2013, 113, 734.

SHARIFI ET AL.
9
[9] G. R. Green, J. M. Evans, A. K. Vong, A. R. Katritzky, C. W. Rees,
E. F. Scriven, Comprehensive Heterocyclic Chemistry II, vol. 5, Pergamon
Press, Oxford 1995, p. 469.
[10] W. O. Foye, Principi Di Chemico Frmaceutica, Piccin, Padova 1991.
[11] C. S. Konkoy, D. B. Fick, S. X. Cai, N. C. Lan, J. F. W. Keana, PCT inter-
national application WO0075123. Chemical Abstracts 2000, 134, 29313a.
[12] A. Burgard, H. Lang, U. Gerlach, Tetrahedron 1999, 55, 7555.
[13] J. M. Evans, C. S. Fake, T. C. Hamilton, R. H. Poyser, G. A. Showell,
J. Med. Chem. 1984, 27, 1127.
[26] W. L. Xie, X. M. Huang, Catal. Lett. 2006, 107, 53.
[27] L. J. Gao, G. Y. Teng, J. H. Lv, G. M. Xiao, Energy Fuel 2010, 24, 646.
[28] S. Hu, Y. Guan, Y. Wang, H. Han, Appl. Energy 2011, 88, 2685.
[29] T. Ando, J. Yamawaki, Chem. Lett. 1979, 1, 45.
[30] J. H. Zhu, Y. Chun, Y. Qin, Xu, Q. H. Microporous Mesoporous Mater.
1998, 24, 19.
[31] F. M. Asseid, C. V. A. Duke, J. M. A. Miller, Can. J. Chem. 1990, 68,
1420.
[32] M. Zahouily, B. Bahlaouane, M. Aadil, A. Rayadh, S. Sebti, Org. Process.
Res. Dev. 2004, 8, 278.
[33] L. Gao, G. Teng, G. Xiao, R. Wei, Biomass Bioenergy 2010, 34, 1283.
[34] J. V. Smith, Chem. Rev. 1998, 88, 149.
[35] L. L. Ames, Am. Mineral. 1960, 45, 689.
[36] H. Sajjadi-Ghotbabadi, S. Javanshir, F. Rostami-Charati, Catal. Lett. 2016,
146, 338.
[37] (a) M. A. Khalilzadeh, A. Hosseini, A. Pilevar, Eur. J. Org. Chem. 2011, 8,
1587. (b) S. Salmanpour, M. A. Khalilzadeh, A. Hosseini, Comb. Chem.
High Throughput Screen. 2013, 16, 339. (c) M. A. Khalilzadeh,
H. Keipour, A. Hosseini, D. Zareyee, New J. Chem. 2014, 38, 42.
(d) S. Hallajian, M. A. Khalilzadeh, M. Tajbakhsh, E. Alipour, Z. Safaei,
Comb. Chem. High Throughput Screen 2015, 18(5), 486.
[38] A. R. Saundane, M. K. Nandibeoor, Monatsh. Chem. 2015, 146, 1751.
[39] A. M. Bidchol, Food Bioprocess Technol. 2011, 4, 1137.
[40] M. Oyaizu, Jpn. J. Nutr. Diet. 1986, 44, 307.
[14] J. M. Evans, C. S. Fake, T. C. Hamilton, R. H. Poyser, E. A. Watts, J. Med.
Chem. 1983, 26, 1582.
[15] A. Afantitis, G. Melagraki, H. Sarimveis, P. A. Koutentis, J. Markopoulos,
O. Igglessi-Markopoulou, Bioorg. Med. Chem. 2006, 14, 6686.
[16] C. Conti, L. P. Monaco, N. Desideri, Bioorg. Med. Chem. 2011, 19, 7357.
[17] W. Kemnitzer, J. Drewe, S. Jiang, H. Zhang, C. Crogan-Grundy,
D. Labreque, M. Bubenick, G. Attardo, R. Denis, S. Lamothe,
H. Gourdeau, B. Tseng, S. Kasibhatla, S. X. Cai, J. Med. Chem. 2008,
51, 417.
[18] A. A. Patchett, R. P. Nargund, Annu. Rep. Med. Chem. 2000, 35, 289.
[19] S. G. Das, J. M. Doshi, D. Tian, S. N. Addo, B. Srinivasan,
D. L. Hermanson, C. Xing, J. Med. Chem. 2009, 52, 5937.
[20] S. Kasibhatla, H. Gourdeau, K. Meerovitch, J. Drewe, S. Reddy, L. Qiu,
H. Zhang, F. Bergeron, D. Bouffard, Q. Yang, J. Herich, S. Lamothe,
S. X. Cai, B. Tseng, Mol. Cancer Ther. 2004, 3, 1365.
[21] (a) S. C. Huang, P. L. Wu, T. S. Wu, Phytochemistry 1997, 44, 179.
(b) R. S. Mali, P. P. Joshi, P. K. Sandhu, A. Manekar-Tilve, J. Chem. Soc.
Perkin Trans. 2002, 1, 137. (c) S. Arunrat, K. Ngampong, K. Boonsong,
P. Sida, W. D. John, F. S. Thomas, N. Yuth, R. Sasarose, Planta Med.
2003, 69, 155. (d) K. Boonsong, K. Ngampong, S. Arunrat, N. Chanita,
Y. Chalobon, Phytother. Res. 2005, 19, 728. (e) C. R. Su, S. F. Yeh,
C. M. Liu, A. G. Damu, T. H. Kuo, P. C. Chiang, K. F. Bastow, K. H. Lee,
T. S. Wu, Bioorg. Med. Chem. 2009, 17, 6137.
[22] (a) M. Gohain, H. T. Johannes, C. B. B. Barend, Tetrahedron Lett. 2013,
54, 3773. (b) Y. Srinivasarao, S. Pyare Lal, G. Singh, Tetrahedron Lett.
2015, 56, 1649. (c) A. Naseem, B. Venkata Babu, Synth. Commun. 2013,
43, 3044. (d) L. Yunkui, Z. Jie, Q. Jianqiang, B. Jiang, X. Zhenyuan,
J. Org. Chem. 2011, 76, 9096.
[41] K. Shimada, K. Fujikawa, N. T. Yahara, J. Agric. Food Chem. 1992,
40, 945.
[42] A. Yildirim, A. Mavi, A. A. Kara, J. Agric. Food Chem. 2001, 49, 4083.
[43] G. C. Yen, P. D. Duh, J. Agric. Food Chem. 1994, 42, 629.
How to cite this article: Sharifi S, Maghsoudlou MT,
Hazeri N, Rostami-Charati F. KF/clinoptilolite
nanoparticles as a novel catalyst for the green synthesis
of chromens using three component reactions of 4-
hydroxycoumarins: Study of antioxidant activity.
J Chin Chem Soc. 2019;1–9. https://doi.org/10.1002/
jccs.201800282
[23] (a) B. Halliwell, Free Radic. Res. 1999, 31, 261. (b) F. Ahmadi,
M. Kadivar, M. Shahedi, Food Chem. 2007, 105, 57.
[24] M. A. Babizhayev, A. I. Deyev, V. N. Yermakovea, I. V. Brikman,
J. Bours, Drugs R D 2004, 5, 125.
[25] L. Liu, M. Meydani, Nutr. Rev. 2002, 60, 368.