Catalyst-free green synthesis and study of antioxidant activity of new pyrazole derivatives

Article abstract of DOI:10.1002/jhet.4004

In this research, a novel procedure for the synthesis of pyrazole derivatives in excellent yields was studied using catalyst-free multicomponent reaction of isoquinoline, activated acetylenic compounds, alkyl bromides, triphenylphosphine and hydrazine in

Full text of DOI:10.1002/jhet.4004

Received: 12 March 2020
DOI: 10.1002/jhet.4004
Revised: 10 April 2020
Accepted: 13 April 2020
A R T I C L E
Catalyst-free green synthesis and study of antioxidant
activity of new pyrazole derivatives
1
2
3
Navisa Tabarsaei
| Naghmeh Faal Hamedani
| Shahin Shafiee
|
4
5
Samira Khandan | Zinatossadat Hossaini
1
Department of Chemistry, Gorgan Branch, Islamic Azad University, Gorgan, Iran
2
Department of Chemistry, Faculty of Valiasr, Tehran Branch, Technical and Vocational University (TVU), Tehran, Iran
Department of Chemistry, Najaf Abad Branch, Islamic Azad University, Tehran, Iran
3
4
5
Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran
Correspondence
Abstract
Navisa Tabarsaei, Department of
Chemistry, Gorgan Branch, Islamic Azad
University, Gorgan, Iran.
In this research, a novel procedure for the synthesis of pyrazole derivatives in excel-
lent yields was studied using catalyst-free multicomponent reaction of isoquinoline,
activated acetylenic compounds, alkyl bromides, triphenylphosphine and hydrazine
in water under ultrasonic irradiation at room temperature. The advantages of this
procedure than to reported methods are short time of reaction, high yields of prod-
uct, easy separation of product, clean mixture of reaction and green media for per-
forming reaction. In addition, because of having pyrazole and isoquinoline core in
the synthesized compounds, in this research, antioxidant activity of some synthe-
sized compounds was investigated.
Email: navisa.tabarsaie@gmail.com
Zinatossadat Hossaini, Department of
Chemistry, Qaemshahr Branch, Islamic
Azad University, Qaemshahr, Iran.
Email: zshossaini@yahoo.com
Funding information
Islamic Azad University of Gorgan and
Qaemshahr
[
11–14]
1
| INTRODUCTION
conventional stirring methods.
It should be men-
tioned that heterocyclic compounds are a highly valuable
and unique class of compounds. These compounds dem-
Sonochemistry as an original and valuable method has
attracted increasing interest in accelerating organic
onstrate a broad spectrum of physical, chemical and bio-
[1–4]
[15,16]
reactions.
This procedure can be very efficient and is
logical characteristics.
In nature, heterocyclic
applicable to a broad variety of practical synthesis. Luche
and coworkers have carried out a number of investiga-
tions, which provided the basis for using sonochemistry
compounds are widely distributed and display an important
part in metabolism because of their structural nucleus occur-
ring in various natural products, including hormones, antibi-
[5–8]
[17–19]
in organic synthesis.
The significant features of the
otics, alkaloids, vitamins and many others.
Among
ultrasound approach in organic reactions are improve-
ment of reaction rates, formation of pure products with
high yields and easier process. This method is also con-
sidered as a help in terms of energy protection and waste
heterocyclic compounds, nitrogen-containing heterocycles are
considerably found as a main structure in an enormous library
of heterocycles and display several employments in natural
[20]
science and other areas of science. In addition, nitrogen-
containing heterocycles are broadly displayed in natural prod-
[
9,10]
decreasing when compared with traditional methods.
[21,22]
Ultrasound has increasingly been used in organic synthe-
sis. A large number of ultrasonic reactions can be carried
out in higher yield, shorter reaction time or milder condi-
tions. It is also observed that reactions under ultrasound
irradiation are commonly easier to work-up than those in
ucts, for instance, vitamins, hormones and alkaloids.
Among them, pyrazole derivatives demonstrate a broad spec-
[23]
trum of biological activities such as anti-tubercular, anti-
[
24]
[22]
[25]
[26,27]
AIDS, anti-malarial, anti-microbial, antitumor,
[28]
[20]
anticancer and antifungal. In addition, pyrazoles have
J Heterocyclic Chem. 2020;1–10.
wileyonlinelibrary.com/journal/jhet
© 2020 Wiley Periodicals LLC
1

2
TABARSAEI ET AL.
[
29]
1
also been found as promising anti-hyperglycemic,
anti-
the H NMR spectrum of 6a exhibited one singlet at 3.85
for methoxy protons, two singlets at 5.32 and 6.23 for
methin proton and one broad singlet at 8.45 for NH proton
along with signals for aromatic moiety at 6.87-8.15 ppm. In
[30]
[31]
[32]
depressant,
ety
anti-convulsant,
anti-pyretic, anti-anxi-
[
33,34]
[35]
and insecticidal agents.
Herein, in continuation of our attempts to expand
new synthetic procedure for important heterocyclic
1
3
the C NMR spectrum, the signals corresponding to the
two carbonyl group of 6a were observed at δ 162.3 and
164.8 ppm. Although there is no information about the
mechanistic details, the reaction can been described by the
mechanism proposed in Scheme 2.
[36–48]
compounds,
we investigated synthesis of pyrazole
derivatives in excellent yields (Scheme 1).
2
| RESULT AND DISCUSSION
First, isoquinoline 1 and activated acetylenic com-
pounds 2 reacted under ultrasonic irradiation and gener-
ate intermediate 7. The reaction of alkyl bromides 3 and
triphenylphosphine 4 produces intermediate 8. Interme-
diate 7 and intermediate 8 react together to produce
intermediate 9. Intermediate 9 convert into ylide 10 by
losing hydrogen and intermolecular cyclization of 10 gen-
erates intermediate 11. Intermediate 12 was produced by
elimination of triphenylphosphine oxide from intermedi-
ate 11. Hydrazine reacts with carbonyl group of 12 and
converts into intermediate 13. Finally, intermolecular
cyclization and elimination of alcohol produce product
6 in excellent yields. These reactions are experimented by
two procedures. In the first procedure, compound 12a
was separated and hydrazine 5 reacts with 12a separately
in water under ultrasonic irradiation after confirmation
of the structure (Scheme 3). The structures of compounds
In this work, generation of pyrazole derivatives 6 in
excellent yield is performed using isoquinoline 1, acti-
vated acetylenic comompouds 2, alkyl bromide 3,
triphenylphosphine 4 and hydrazine 5 in water at room
temperature under ultrasonic irradiation condition in
short time (Scheme 1).
In the starting stage of this work, catalyst-free reaction of
isoquinoline 1, dimethyl acetylenedicarboxylate 2a, ethyl
bromopyruvate 3a, triphenylphosphine 4 and hydrazine
5
was employed as a sample reaction to achieve the opti-
mum conditions (Table 1). It should been mentioned that
these reactions are experimented in both ultrasonic irradia-
tion and conventional conditions and results were exhibited
in Table 1. Surprisingly the yield of compound 6a was
obtained as 85% under ultrasonic irradiation in short time at
room temperature (Table 1). By increasing the temperature,
there was no significant change in the yield of reaction.
The structures of compounds 6 were confirmed by IR,
1
13
12a were confirmed by IR, H NMR, C NMR and mass
1
spectral data. The H NMR spectrum of 12a exhibited
two singlets at 3.86 and 3.98 ppm for methoxy protons,
one singlet at 5.32 for CH proton, and one singlet at
1
13
H NMR, C NMR and mass spectral data. For example,
R
N
R
R''
))))
+
+
+ PPh3 NH -NH2
+
2
Br
N
H O, r.t., 1 h
R''
2
O
CO R'
2
N
N
H
1
2
3
4
5
6
R
R'
6
R''
CO Et
Yield % of 6
a CO Me
Me
Et
2
2
95
b CO Et
CO Et
85
2
2
92
c
d
e
CO Et
H
Me
Me
2
90
90
CO Me
4-MeO-C H
2
6
4
H
Me
Et
4-MeO-C
6
H
4
87
90
87
f
CO Et
4-MeO-C H
2
6
4
g
Me
CO Me
4-Me-C H
4
2
6
h
Et
4-Me-C H
85
83
80
CO Et
2
6
4
i
j
CO Me
Me
Me
4-Br-C H
4
SCHEME 1 Catalyst free
synthesis of pyrazoles 6 under
ultrasonic irradiation
2
6
CO Me
4-NO -C H
2 6 4
2

TABARSAEI ET AL.
3
TABLE 1
reaction conditions for synthesis of 6a
Optimization the
Time/h
Conventional conditions
Yield (%)
Time/min
Ultrasonic irradiation
Yield (%)
Entry
Solvent
1
2
3
4
5
6
7
-
6
2
3
2
5
2
2
45
75
48
56
25
60
63
2
58
95
75
80
40
78
80
H
2
O
60
2
Toluene
CH CN
DMF
CH Cl
CHCl
3
2
5
2
2
2
3
2
R
))))
CO R'
2
+
+
N
N
H
CO R'
2
R
2
7
1
R''
)
)))
_
Br
PPh3
+
3
R''
+
Ph P
_
O
HBr
O
3
4
8
CO R'
2
_
+
+
3
R''
H
H
+
N
Ph P
H
N
+
O
O
N
+
O
R
_
R''
R
PPh3
R''
R
PPh3
OR'
OR'
7
8
O
O
9
10
_
Ph P=O
3
+
5
N
R
N
R
N
R
R''OC
R''
R''
+
Ph P
3
O
OR'
O
OR'
_
N
OR'
NH2
12
11
13
_
R''OH
6
N
R
R''
OR'
N
N
H
H
14
SCHEME 2 proposed mechanism for preparation of 6
6
.12 ppm for CH proton along with signals for aromatic
In the second procedure, all of compounds added
13
moiety. In the
corresponding to the three carbonyl group of 6a were
observed at δ 164.3, 165.6 and 176.6 ppm.
C
NMR spectrum, the signals
together in one-pot and compounds 6 were produced.
The results show that the product in two procedures is
the same but the yield of reaction is completely different.

4
TABARSAEI ET AL.
As shown in results in Scheme 3, the yield of reactions in
the second procedure is more than the first procedure,
which is one of the advantages of multicomponent reac-
tions. In multi-step reactions, the yield of final product
due to separation of some intermediate is low.
Under similar conditions, synthesis of another pyrazole
derivatives 16 and 17, respectively, in good yield is
carried out using quinoline or pyridine 15, dimethyl
acetylenedicarboxylate 2a, alkyl bromide 3, triphenyl-
phosphine 4 and hydrazine 5 in water at room tempera-
ture under ultrasonic irradiation condition in short
time (Scheme 4).
for methoxy protons, one singlet at 5.62 (1 H, d,
J = 6.5 Hz, CH) ppm for -CH proton, and one singlet at
3
6.27 ppm for CH proton along with signals for aromatic
13
moiety. In the
C NMR spectrum, the signals
corresponding to CH group and the two carbonyl group
of 16a were observed at δ 48.5 (CH), 161.4 (C O), 167.3
(C O) ppm, respectively. In addition, the structures of
1
13
compounds 17a were confirmed by IR, H NMR,
C
1
NMR and mass spectral data. The H NMR spectrum of
17a showed exhibited one singlet at 3.78 ppm for met-
3
hoxy protons, one singlet at 5.45 (1 H, d, J = 7.5 Hz, CH)
ppm for -CH proton, one singlet at 6.32 ppm for CH
proton and one singlet at 8.52 for NH proton along with
The structures of compounds 16a were confirmed by
1
13
1
13
IR, H NMR, C NMR and mass spectral data. The H
signals for aromatic moiety. In the C NMR spectrum,
NMR spectrum of 16a exhibited one singlet at 3.87 ppm
the signals corresponding to
CH group and two
First pathways
Second pathways
CO Me
2
H O, ))))
H O, ))))
2
CO Et
2
2
N
+
+
Br
CO Me + NH -NH
2
2
2
r.t., 75 min
5%
N
r.t., 60 min
O
EtO C
2
CO Me
7
95%
2
3
a
1
2a
O
OMe
PPh3
NH -NH
+
2
2
4
1
2a
5
5
N
CO Me
2
EtO C
2
N
N
H
6
a
SCHEME 3 Synthesis of pyrazole 6a by two procedures
R
N
N
CO Me
N
H
2
MeO C
2
R'
))))
+
+
+ PPh3 NH -NH
16
Br
+
2
2
H O, r.t., 1.5 h
N
O
2
CO Me
2
R
15
2
3
4
5
N
N
N
H
MeO C
2
17
R
Yield % of 16
Yield % of 17
16, 17
a
CO Et
90
87
95
92
2
b
4-MeO-C H4
6
SCHEME 4 Synthesis of pyrazole 16 and 17 using quinoline and pyridine, respectively

TABARSAEI ET AL.
5
carbonyl group of 16a were observed at δ 46.3 (CH) and
this research, the antioxidant ability or power of com-
pounds 6a–d for taking free radicals was compared with
synthesized antioxidants such as BHT and TBHQ at dif-
ferent concentrations (Figure 1).
1
61.2 (C O), 164.3 (C O) ppm, respectively.
2
.1 | Study of antioxidant activity
employing Diphenyl-
-picrylhydrazyl (DPPH)
As shown in Figure 1, the new synthesized com-
pounds in all concentrations (200-1000 ppm) have good
distinctions than to BHT and TBHQ but, at concentration
2
(
1000 ppm), have excellent free radical trapping power
For the confirmation of antioxidant ability or power of
compounds to take free radicals of some synthesized
compounds and their antioxidant properties in foods
than to BHT and TBHQ. Among selected synthesized
compounds, 6c was shown excellent radical trapping
activity relative to standards (BHT and TBHQ).
[
49,50]
and biological systems,
diphenyl-2-picrylhydrazyl
(
DPPH) radical trapping experiment is widely used. In
3
+
this experiment, taking one electron or the hydrogen
atom of synthesized compounds was performed by
DPPH radical and shows a valuation of antioxidant
capacity basis of free radical trapping. The antioxidant
ability of 6a–d was investigated based on their electron
or hydrogen donating powers to the DPPH radical. The
absorption of DPPH radical was observed in area
2.2 | Reducing power of ferric ions (Fe )
by some synthesized compounds (FRAP)
3+
The power of reducing ferric ions (Fe ) by some pyrazole
derivatives such as 6a–d is calculated by the amount of
reduction of Fe /ferricyanide complex to the Fe / ferrous
at 700 nm. As shown in Figure 2, in this test, compound
6c was shown very good reducing ability than to standard
antioxidants such as BHT and TBHQ.
3+
2+
[51]
5
17 nm but when DPPH radical is decreased using an
antioxidant or radical types, its absorption decreases. In
FIGURE 1 Radical scavenging
activity of 6a–d [Color figure can be
viewed at wileyonlinelibrary.com]
FIGURE 2 Reducing power of
3
+
ferric ions (Fe ) (FRAP) by compounds
a–d [Color figure can be viewed at
wileyonlinelibrary.com]
6

6
TABARSAEI ET AL.
3
In summary, multicomponent reaction of isoquinoline,
CH), 7.12 (1 H, d, J = 7.6 Hz, CH), 7.25 (1 H, t,
3
3
quinoline or pyridine with activated acetylenic compounds,
alkyl bromides, triphenylphosphine and hydrazine in water
under ultrasonic irradiation at room temperature produced
pyrazole derivatives in excellent yields. Also, the antioxi-
dant activities of 6a–d were evaluated by DPPH radical
scavenging and ferric reducing power analyzes. The com-
pounds 6c exhibit excellent DPPH radical scavenging activ-
ity and FRAP compared with synthetic antioxidants BHT
and TBHQ. The significant benefits of our method are
green reaction conditions, high yield, short reaction time
and easy work-up, which are in good agreement with some
principles of green chemistry.
J = 7.6 Hz, CH), 7.42 (1 H, t, J = 7.6 Hz, CH), 7.65 (1 H,
d, J = 7.8 Hz, CH), 8.15 (1 H, d, J = 7.6 Hz, CH), 8.45
(1 H, s, NH) ppm. C NMR (125.7 MHz, CDCl ): 13.9
(Me), 51.3 (CH), 52.6 (MeO), 62.4 (CH O), 86.7 (CH),
106.3 (CH), 115.8 (C), 125.3 (CH), 126.6 (CH), 127.2
(CH), 127.8 (CH), 128.3 (CH), 134.2 (C), 138.6 (C), 140.2
(C), 141.5 (C), 142.3 (C), 162.3 (C O), 164.8 (C O) ppm.
MS (EI, 70 eV): m/z (%) = 351 (M , 15), 320 (68),
129 (100), 31 (100). Anal. calcd for C H N O
17 3 4
3
3
13
3
2
+
19
(351.36): C, 64.95; H, 4.88; N, 11.96. Found: C, 65.12; H,
4.98; N, 12.18%.
0
0
Diethy-5-methyl3,12b-dihydropyrazolo[4 ,3 :3,4]pyrido
[
2,1-a]isoquinoline-1,5-dicarboxylate (6b). Yellow powder,
ꢀ
ꢀ
mp 166 C-168 C, Yield: 0.67 g (92%). IR (KBr)
(νmax/cm ): 1738, 1735, 1692, 1585, 1487, 1286 cm . H
NMR (500 MHz, CDCl ): 1.25 (3 H, t, J = 7.4 Hz, CH ),
1.32 (3 H, t, J = 7.4 Hz, CH ), 4.23 (2 H, q, J = 7.4 Hz,
CH O), 4.28 (2 H, q, J = 7.4 Hz, CH O), 5.35 (1 H, s,
CH), 6.24 (1 H, s, CH), 6.93 (1 H, d, J = 7.7 Hz, CH),
7.15 (1 H, d, J = 7.7 Hz, CH), 7.32 (1 H, t, J = 7.7 Hz,
−
1
−1 1
3
| EXPERIMENTAL
3
3
3
3
3
All chemicals used in this work were prepared from
Fluka (Buchs, Switzerland) and were used without fur-
ther purification. Melting points were measured on an
Electrothermal 9100 apparatus. Elemental analyses for C,
H and N were performed using a Heraeus CHN O-Rapid
analyzer. Mass spectra were recorded on a FINNIGAN-
MAT 8430 spectrometer operating at an ionization poten-
tial of 70 eV. IR spectra were measured on a Shimadzu
3
3
2
2
3
3
3
3
CH), 7.46 (1 H, t, J = 7.6 Hz, CH), 7.68 (1 H, d,
3
3
J = 7.8 Hz, CH), 8.17 (1 H, d, J = 7.6 Hz, CH), 8.46
13
(1 H, s, NH) ppm. C NMR (125.7 MHz, CDCl ): 13.9
3
(Me), 14.2 (Me), 51.3 (CH), 61.5 (CH O), 62.6 (CH O),
2
2
1
13
IR-460 spectrometer. H and C NMR spectra were mea-
sured with a BRUKER DRX-500 AVANCE spectrometer
87.3 (CH), 106.5 (CH), 116.3 (C), 125.5 (CH), 127.2 (CH),
127.8 (CH), 128.3 (CH), 128.7 (CH), 134.5 (C), 139.3 (C),
140.5 (C), 141.6 (C), 142.7 (C), 162.5 (C O), 165.2 (C O)
1
13
at 500.1 and 125.8 MHz, respectively. H and C spectra
+
were obtained for solutions in CDCl using TMS as inter-
ppm. MS (EI, 70 eV): m/z (%) = 365 (M , 15), 320 (68),
3
nal standard or 85% H PO as external standard.
129 (100), 45 (100). Anal. calcd for C H N O
20 19 3 4
3
4
(
365.39): C, 65.74; H, 5.24; N, 11.50. Found: C, 65.95; H,
.43; N, 11.67%.
Ethyl 3,12b-dihydropyrazolo[4 ,3 :3,4]pyrido[2,1-a]
isoquinoline-1-carboxylate (6c). Pale yellow powder, mp
5
0
0
3
.1 | General procedure for preparation
of compounds 6a–j
ꢀ
ꢀ
−1
1
42 C-144 C, Yield: 0.53 g (90%). IR (KBr) (ν /cm ):
max
−
1 1
The mixture of isoquinoline 1 (2 mmol) and activated
acetylenic compounds 2 (2 mmol) stirred in water (3 mL)
under ultrasonic irradiation. After 10 min the mixture of
alkyl bromide 3 and triphenylphosphine 4 that is mixed
for 20 min in water (3 mL) under ultrasonic irradiation
was added to previous mixture. After 20 minutes, hydra-
zine (2.5 mmol) was added to mixture and stirred for
1737, 1697, 1569, 1484, 1287 cm . H NMR (500 MHz,
3
CDCl ): 1.34 (3 H, t, J = 7.4 Hz, CH ), 4.24 (2 H, q,
3
3
3
J = 7.4 Hz, CH O), 5.24 (1 H, s, CH), 5.63 (1 H, d,
2
3
3
J = 6.5 Hz, CH), 6.23 (1 H, d, J = 6.5 Hz, CH), 6.65
3
3
(1 H, d, J = 6.5 Hz, CH), 7.15 (1 H, d, J = 6.5 Hz, CH),
7.35 (1 H, t, J = 7.7 Hz, CH), 7.42 (1 H, t, J = 7.6 Hz,
CH), 7.65 (1 H, d, J = 7.8 Hz, CH), 8.12 (1 H, d, J = 7.6 Hz,
3
3
3
3
13
1
0 minutes under ultrasonic irradiation. After comple-
CH), 8.38 (1 H, s, NH) ppm. C NMR (125.7 MHz, CDCl3):
tion, the reaction is monitored by TLC, and the solid resi-
14.0 (Me), 51.6 (CH), 61.7 (CH O), 98.3 (CH), 106.7 (CH),
2
due was separated by filtration and washed with Et O to
109.2 (C), 123.4 (CH), 125.6 (CH), 126.7 (CH), 127.2 (CH),
127.8 (CH), 128.2 (CH), 132.3 (C), 136.4 (C), 138.2 (C),
140.4 (C), 163.7 (C O) ppm. MS (EI, 70 eV): m/z (%) = 293
2
afforded pure title compound 6.
0
0
1-Ethy-5-methyl3,12b-dihydropyrazolo[4 ,3 :3,4]pyrido
+
[
2,1-a]isoquinoline-1,5-dicarboxylate (6a). Yellow powder,
(M , 10), 248 (72), 129 (100), 45 (100). Anal. calcd for
ꢀ
ꢀ
mp 163 C-165 C, Yield: 0.67 g (95%). IR (KBr)
C H N O (293.32): C, 69.61; H, 5.15; N, 14.33. Found: C,
17 15 3 2
−
1
−1 1
(
νmax/cm ): 1739, 1738, 1695, 1587, 1489, 1295 cm . H
69.83; H, 5.36; N, 14.52%.
3
NMR (500 MHz, CDCl ): 1.28 (3 H, t, J = 7.4 Hz, CH ),
3
Methy11-(4-methoxy phenyl) 3,12b-dihydropyrazolo
3
3
3
0 0
.85 (3 H, s, MeO), 4.26 (2 H, q, J = 7.4 Hz, CH O), 5.32
[4 ,3 :3,4]pyrido[2,1-a]isoquinoline-5-carboxylate (6d). Pale
2
3
ꢀ ꢀ
yellow powder, mp 146 C-148 C, Yield: 0.69 g (90%). IR
(1 H, s, CH), 6.23 (1 H, s, CH), 6.87 (1 H, d, J = 7.6 Hz,

TABARSAEI ET AL.
7
−
1
−1 1
(
KBr) (νmax/cm ): 1739, 1695, 1568, 1486, 1293 cm . H
C H N O (327.38): C, 77.04; H, 5.23; N, 12.84.
21
17 3
NMR (500 MHz, CDCl ): 3.75 (3 H, s, MeO), 3.87 (3 H, s,
MeO), 5.36 (1 H, s, CH), 6.03 (1 H, d, J = 6.8 Hz, CH),
Found: C, 77.23; H, 5.42; N, 12.98%.
3
3
Methy11-(4-methyl phenyl) 3,12b-dihydropyrazolo
3
0 0
6
(
7
.35 (1 H, s, CH), 6.97 (2 H, d, J = 7.6 Hz, 2 CH), 7.08
[4 ,3 :3,4]pyrido[2,1-a]isoquinoline-5-carboxylate (6g). Yel-
3
3
ꢀ ꢀ
low powder, mp 137 C-139 C, Yield: 0.69 g (87%). IR
1 H, d, J = 7.8 Hz, CH), 7.23 (1 H, t, J = 7.8 Hz, CH),
.35 (1 H, t, J = 7.8 Hz, CH), 7.52 (1 H, d, J = 7.8 Hz,
CH), 7.67 (2 H, d, J = 7.6 Hz, 2 CH), 7.96 (1 H, d,
J = 7.6 Hz, CH), 8.42 (1 H, s, NH) ppm. C NMR
125.7 MHz, CDCl ): 52.3 (MeO), 54.6 (CH), 55.6 (MeO),
3
3
−1
−1 1
(KBr) (νmax/cm ): 1736, 1687, 1585, 1487, 1295 cm . H
3
NMR (500 MHz, CDCl ): 2.34 (3 H, s, Me), 3.78 (3 H, s,
3
3
13
3
MeO), 5.42 (1 H, s, CH), 6.24 (1 H, d, J = 6.5 Hz, CH),
3
(
6.37 (1 H, s, CH), 7.05 (1 H, d, J = 6.5 Hz, CH), 7.23
3
3
3
9
1
7.2 (CH), 105.7 (CH), 113.4 (2 CH), 115.6 (C), 124.7 (CH),
27.2 (2 CH), 127.6 (CH), 127.9 (CH), 128.3 (CH), 128.5
(1 H, t, J = 7.6 Hz, CH), 7.32 (1 H, t, J = 7.6 Hz, CH),
3
3
7.42 (2 H, d, J = 7.8 Hz, 2 CH), 7.54 (1 H, d, J = 7.7 Hz,
3
(CH), 129.2 (C), 130.3 (C), 135.2 (C), 139.2 (C), 140.3 (C),
CH), 7.83 (2 H, d, J = 7.6 Hz, 2 CH), 7.93 (1 H, d,
3
13
1
47.2 (C), 156.3 (C), 164.2 (C O) ppm. MS (EI, 70 eV): m/z
J = 7.6 Hz, CH), 8.38 (1 H, s, NH) ppm. C NMR
+
(%) = 385 (M , 15), 354 (48), 129 (100), 31 (100). Anal.
(125.7 MHz, CDCl ): 22.3 (Me), 51.4 (MeO), 53.8 (CH),
3
calcd for C H N O (385.42): C, 71.67; H, 4.97; N, 10.90.
Found: C, 71.84; H, 5.18; N, 10.90%.
96.6 (CH), 104.6 (CH), 114.6 (C), 124.2 (CH), 125.4 (CH),
127.3 (2 CH), 127.8 (CH), 128.2 (CH), 128.6 (CH), 129.2
(C), 129.7 (2 CH), 133.2 (C), 135.6 (C), 139.2 (C), 140.2
(C), 141.2 (C), 147.5 (C), 163.2 (C O) ppm. MS (EI,
23 19 3 3
Ethy11-(4-methoxy phenyl) 3,12b-dihydropyrazolo
0 0
[
4 ,3 :3,4]pyrido[2,1-a]isoquinoline-5-carboxylate (6e). Pale
ꢀ
ꢀ
+
yellow powder, mp 153 C-154 C, Yield: 0.72 g (90%). IR
KBr) (νmax/cm ): 1742, 1697, 1578, 1487, 1295 cm . H
NMR (500 MHz, CDCl ): 1.23 (3 H, t, J = 7.4 Hz, CH ),
.34 (2 H, q, J = 7.4 Hz, CH O), 5.28 (1 H, s, CH), 6.12
2
1 H, d, J = 6.8 Hz, CH), 6.42 (1 H, s, CH), 7.03 (2 H, d,
J = 7.6 Hz, 2 CH), 7.15 (1 H, d, J = 7.8 Hz, CH), 7.34
1 H, t, J = 7.8 Hz, CH), 7.48 (1 H, t, J = 7.8 Hz, CH),
.56 (1 H, d, J = 7.8 Hz, CH), 7.73 (2 H, d, J = 7.6 Hz,
70 eV): m/z (%) = 369 (M , 15), 338 (68), 129 (100),
−
1
−1 1
(
31 (100). Anal. calcd for C H N O (369.42): C,
23
19 3 2
3
74.78; H, 5.18; N, 11.37. Found: C, 74.93; H,
5.34; N, 11.57%.
3
3
3
4
3
(
Ethy11-(4-methyl
[4 ,3 :3,4]pyrido[2,1-a]isoquinoline-5-carboxylate (6h). Yel-
phenyl)
3,12b-dihydropyrazolo
3
3
0
0
3
3
ꢀ ꢀ
(
7
2
low powder, mp 142 C-144 C, Yield: 0.72 g (85%). IR
3
3
−1
−1 1
(KBr) (νmax/cm ): 1738, 1695, 1569, 1485, 1293 cm . H
3
3
CH), 8.06 (1 H, d, J = 7.6 Hz, CH), 8.45 (1 H, s, NH)
ppm. C NMR (125.7 MHz, CDCl ): 13.8 (Me), 53.8
NMR (500 MHz, CDCl ): 1.25 (3 H, t, J = 7.4 Hz, CH ),
2.36 (3 H, s, Me), 4.25 (2 H, q, J = 7.4 Hz, CH O), 5.23
(1 H, s, CH), 6.09 (1 H, d, J = 6.7 Hz, CH), 6.26 (1 H, s,
CH), 7.08 (1 H, d, J = 6.7 Hz, CH), 7.25 (1 H, t,
3
3
13
3
3
2
3
(
CH), 55.7 (MeO), 61.8 (CH O), 96.7 (CH), 106.4 (CH),
2
3
1
(
1
13.7 (2 CH), 116.3 (C), 125.3 (CH), 126.8 (2 CH), 127.8
CH), 128.2 (CH), 128.5 (CH), 128.7 (CH), 129.6 (C),
30.5 (C), 135.6 (C), 139.4 (C), 140.5 (C), 147.7 (C), 156.5
3
3
J = 7.6 Hz, CH), 7.37 (1 H, t, J = 7.6 Hz, CH), 7.45 (2 H,
3
3
d, J = 7.8 Hz, 2 CH), 7.56 (1 H, d, J = 7.7 Hz, CH), 7.87
3
3
(
(
C), 163.8 (C O) ppm. MS (EI, 70 eV): m/z (%) = 399
M , 15), 354 (68), 129 (100), 45 (100). Anal. calcd for
(2 H, d, J = 7.6 Hz, 2 CH), 7.96 (1 H, d, J = 7.6 Hz,
+
13
CH), 8.42 (1 H, s, NH). C NMR (125.7 MHz, CDCl3):
C H N O (399.44): C, 72.16; H, 5.30; N, 10.52.
14.0 (Me), 22.3 (Me), 54.3 (CH), 61.5 (CH O), 96.5 (CH),
24
21
3
3
2
Found: C, 72.34; H, 5.43; N, 10.73%.
-(4-methoxy phenyl) 3,12b-dihydropyrazolo[4 ,3 :3,4]
105.8 (CH), 116.3 (C), 124.8 (CH), 125.7 (CH), 127.2
(2 CH), 127.6 (CH), 128.0 (CH), 128.3 (CH), 129.2 (2 CH),
129.6 (C), 134.2 (C), 137.2 (C), 139.4 (C), 140.2 (C), 141.5
(C), 147.3 (C), 164.3 (C O) ppm. MS (EI, 70 eV): m/z
0
0
1
ꢀ
pyrido[2,1-a]isoquinoline (6f). Yellow powder, mp 187 C-
ꢀ
−1
1
1
89 C, Yield: 0.57 g (87%). IR (KBr) (ν /cm ): 1695,
max
−
1 1
+
624, 1567, 1458, 1236 cm . H NMR (500 MHz, CDCl ):
(%) = 399 (M , 15), 354 (68), 129 (100), 45 (100). Anal.
3
3
.85 (3 H, s, MeO), 5.14 (1 H, s, CH), 6.05 (1 H, d,
calcd for C H N O (383.44): C, 75.18; H, 5.52; N, 10.96.
Found: C, 75.32; H, 5.67; N, 11.18%.
24
21 3 2
3
3
J = 6.7 Hz, CH), 6.25 (1 H, d, J = 6.8 Hz, CH), 6.42
3
3
(1 H, d, J = 6.7 Hz, CH), 6.63 (1 H, d, J = 6.8 Hz, CH),
Methy11-(4-bromophenyl)
3,12b-dihydropyrazolo
3
3
0 0
6
.75 (2 H, d, J = 7.6 Hz, 2 CH), 7.17 (1 H, t, J = 7.8 Hz,
[4 ,3 :3,4]pyrido[2,1-a]isoquinoline-5-carboxylate (6i). Yel-
3
ꢀ ꢀ
low powder, mp 183 C-185 C, Yield: 0.69 g (83%). IR
CH), 7.28 (1 H, t, J = 7.8 Hz, CH), 7.42 (1 H, d,
3
3
−1
−1 1
J = 7.8 Hz, CH), 7.63 (2 H, d, J = 7.8 Hz, CH), 7.85
(KBr) (νmax/cm ): 1735, 1696, 1597, 1492, 1292 cm . H
3
13
(1 H, d, J = 7.6 Hz, CH), 8.45 (1 H, s, NH) ppm.
C
NMR (500 MHz, CDCl ): 3.75 (3 H, s, MeO), 5.18 (1 H, s,
3
3
NMR (125.7 MHz, CDCl ): 55.7 (MeO), 56.3 (CH), 98.6
CH), 6.09 (1 H, d, J = 6.7 Hz, CH), 6.25 (1 H, s, CH),
3
3
3
(CH), 105.6 (CH), 112.2 (C), 113.5 (2 CH), 123.4 (CH),
7.08 (1 H, d, J = 6.7 Hz, CH), 7.18 (1 H, t, J = 7.6 Hz,
3
1
24.8 (CH), 126.8 (2 CH), 127.3 (CH), 127.8 (CH), 128.4
CH), 7.29 (1 H, t, J = 7.6 Hz, CH), 7.35 (2 H, d,
J = 7.7 Hz, 2 CH), 7.46 (2 H, d, J = 7.7 Hz, 2 CH), 7.63
(1 H, d, J = 7.6 Hz, CH), 7.87 (1 H, d, J = 7.6 Hz, CH),
8.24 (1 H, s, NH) ppm. C NMR (125.7 MHz, CDCl3):
3
3
(
(
(
CH), 128.8 (CH), 129.3 (C), 136.4 (C), 138.4 (C), 140.7
C), 147.2 (C), 158.9 (C) ppm. MS (EI, 70 eV): m/z
%) = 327 (M , 10), 198 (84), 129 (100). Anal. calcd for
3
3
+
13

8
TABARSAEI ET AL.
5
1
1.6 (MeO), 54.8 (CH), 96.2 (CH), 104.5 (C), 105.7 (CH),
24.3 (C), 125.2 (CH), 126.3 (CH), 127.2 (CH), 127.6
10 minutes the mixture of alkyl bromide 3 and
triphenylphosphine 4 that is mixed for 20 minutes in
water (3 mL) under ultrasonic irradiation. After
20 minutes, hydrazine (2.5 mmol) was added to mixture
and stirred for 10 minutes under ultrasonic irradiation.
After completion, the reaction is monitored by TLC, and
the solid residue was separated by filtration and washed
(
1
CH), 128.2 (CH), 128.5 (2 CH), 128.7 (C), 130.6 (2 CH),
34.3 (C), 135.8 (C), 139.2 (C), 140.3 (C), 147.7 (C), 161.6
+
(C O) ppm. MS (EI, 70 eV): m/z (%) = 436 (M +2, 15),
+
4
34 (M , 15), 403 (56), 129 (100), 31 (100). Anal. calcd for
C H BrN O (434.29): C, 60.84; H, 3.71; N, 9.68.
22
16
3 2
Found: C, 60.96; H, 3.87; N, 9.85%.
with Et O to afforded pure title compound 16 and 17,
2
Methy11-(4-nitro
4 ,3 :3,4]pyrido[2,1-a]isoquinoline-5-carboxylate (6j). Yel-
phenyl)
3,12b-dihydropyrazolo
respectively.
0
0
0
0
[
3-Ethy-11-methyl1,3b-dihydropyrazolo[4 ,3 :3,4]pyrido
ꢀ
ꢀ
low powder, mp 198 C-200 C, Yield: 0.64 g (80%). IR
[1,2-a]quinoline-3,11-dicarboxylate (16a). Yellow powder,
−
1
−1
1
ꢀ ꢀ
mp 152 C-154 C, Yield: 0.63 g (90%). IR (KBr)
(
KBr) (νmax/cm ): 1736, 1687, 1585, 1487, 1295 cm . H
−
1
−1 1
NMR (500 MHz, CDCl ): 3.76 (3 H, s, MeO), 5.24 (1 H, s,
(νmax/cm ): 1742, 1740, 1697, 1586, 1487, 1292 cm . H
3
3
3
CH), 5.89 (1 H, d, J = 6.8 Hz, CH), 6.23 (1 H, s, CH),
NMR (500 MHz, CDCl ): 1.25 (3 H, t, J = 7.4 Hz, CH ),
3
3
3
3
3
7
.07 (1 H, d, J = 6.8 Hz, CH), 7.22 (1 H, t, J = 7.6 Hz,
3.87 (3 H, s, MeO), 4.25 (2 H, q, J = 7.4 Hz, CH O), 5.62
2
3
3
CH), 7.35 (1 H, t, J = 7.6 Hz, CH), 7.43 (1 H, d,
(1 H, d, J = 6.5 Hz, CH), 6.27 (1 H, s, CH), 6.78 (1 H, d,
3
3
3
3
J = 7.7 Hz, CH), 7.56 (2 H, d, J = 7.8 Hz, 2 CH), 7.86
J = 6.8 Hz, CH), 7.06 (1 H, t, J = 7.6 Hz, CH), 7.18 (1 H,
3
3
3
3
(
1 H, d, J = 7.7 Hz, CH), 8.18 (2 H, d, J = 7.6 Hz, 2 CH),
d, J = 7.6 Hz, CH), 7.34 (1 H, t, J = 7.6 Hz, CH), 7.68
(1 H, d, J = 7.8 Hz, CH), 7.86 (1 H, d, J = 7.6 Hz, CH),
13
3
3
8
5
1
.53 (1 H, s, NH) ppm. C NMR (125.7 MHz, CDCl3):
1.8 (MeO), 54.3 (CH), 96.7 (CH), 105.3 (CH), 117.4 (C),
23.2 (2 CH), 125.2 (CH), 126.3 (CH), 127.5 (CH), 128.3
13
8.48 (1 H, s, NH) ppm. C NMR (125.7 MHz, CDCl3):
14.2 (Me), 48.5 (CH), 52.4 (MeO), 61.3 (CH O), 95.4
2
(
1
CH), 128.5 (CH), 129.5 (2 CH), 129.6 (C), 135.4 (C),
(CH), 109.2 (C), 117.2 (CH), 118.6 (CH), 122.3 (CH),
130.2 (C), 130.8 (CH), 131.2 (C), 131.6 (C), 132.3 (C),
133.4 (CH), 134.2 (CH), 141.2 (C), 161.4 (C O), 167.3
39.3 (C), 140.2 (C), 141.4 (C), 147.3 (C), 149.2 (C), 161.6
+
(
3
C O) ppm. MS (EI, 70 eV): m/z (%) = 400 (M , 15),
69 (86), 129 (100), 31 (100). Anal. calcd for C H N O
16 4 4
+
(C O) ppm. MS (EI, 70 eV): m/z (%) = 351 (M , 15),
22
(400.39): C, 66.00; H, 4.03; N, 13.99. Found: C, 66.23; H,
320 (84), 129 (100), 31 (100). Anal. calcd for C H N O
17 3 4
19
4
.18; N, 14.18%.
Spectral data of intermediate 12a. Methyl 1-(2-ethoxy-
-oxoacetyl)-2-methoxy-11bH-pyrido[2,1-a]isoquinoline-
(351.36): C, 64.95; H, 4.88; N, 11.96. Found: C, 65.16; H,
5.02; N, 12.23%.
2
4
Methy3-(4-methoxy
[4 ,3 :3,4]pyrido[1,2-a]quinoline-11-carboxylate (16b). Pale
phenyl)
1,3b-dihydropyrazolo
ꢀ
ꢀ
0
0
-carboxylate (12a): Yellow powder, mp 158 C-160 C,
−
1
ꢀ ꢀ
Yield: 0.64 g (87%). IR (KBr) (ν /cm ): 1739, 1738,
yellow powder, mp 158 C-160 C, Yield: 0.67 g (87%). IR
max
1
−
1
−1
−1 1
1
725, 1695, 1587, 1489, 1295 cm . H NMR (500 MHz,
(KBr) (νmax/cm ): 1738, 1692, 1575, 1487, 1295 cm . H
3
CDCl ): 1.36 (3 H, t, J = 7.4 Hz, CH ), 3.86 (3 H, s,
MeO), 3.98 (3 H, s, MeO), 4.35-4.44 (2 H, m, CH O), 5.32
NMR (500 MHz, CDCl ): 3.78 (3 H, s, MeO), 3.85 (3 H, s,
3
3
3
3
MeO), 5.24 (1 H, d, J = 6.4 Hz, CH), 6.28 (1 H, d,
2
3
3
(1 H, s, CH), 6.12 (1 H, s, CH), 7.33 (1 H, d, J = 7.6 Hz,
J = 6.8 Hz, CH), 6.47 (1 H, s, CH), 6.98 (2 H, d,
3
3
3
CH), 7.61-7.81 (3 H, m, 3 CH), 8.77 (1 H, d, J = 7.8 Hz,
J = 7.6 Hz, 2 CH), 7.12 (1 H, t, J = 7.6 Hz, CH), 7.25
3
13
3
3
CH), 9.40 (1 H, d, J = 7.6 Hz, CH) ppm. C NMR
125.7 MHz, CDCl ): 13.9 (Me), 41.2 (CH), 52.6 (MeO),
(1 H, d, J = 7.6 Hz, CH), 7.38 (1 H, t, J = 7.8 Hz, CH),
7.59 (1 H, d, J = 7.6 Hz, CH), 7.74 (2 H, d, J = 7.6 Hz,
2 CH), 7.86 (1 H, d, J = 7.6 Hz, CH), 8.53 (1 H, s, NH)
ppm. C NMR (125.7 MHz, CDCl ): 49.3 (CH), 52.6
3
3
(
3
3
5
8.6 (MeO), 62.7 (CH O), 101.9 (CH), 116.6 (CH), 119.1
2
13
(
(
(
C), 123.8 (C), 124.3 (CH), 125.7 (CH), 127.3 (CH), 128.4
CH), 129.4 (CH), 130.1 (C), 133.8 (C), 160.6 (C), 164.3
C O), 165.6 (C O), 176.6 (C O) ppm. MS (EI, 70 eV):
3
(MeO), 55.7 (MeO), 98.4 (CH), 112.4 (C), 113.6 (2 CH),
117.2 (CH), 119.2 (CH), 122.6 (CH), 126.8 (2 CH), 127.2
(C), 130.4 (C), 131.2 (C), 131.8 (CH), 132.3 (C), 133.4
(CH), 134.2 (CH), 140.6 (C), 145.6 (C), 158.3 (C), 165.7
+
m/z (%) = 369 (M , 15), 338 (56), 129 (100), 31 (100).
Anal. calcd for C H NO (369.37): C, 65.03; H, 5.18; N,
20
19
6
+
3
.79. Found: C, 65.18; H, 5.34; N, 3.92%.
(C O) ppm. MS (EI, 70 eV): m/z (%) = 385 (M , 15),
3
54 (62), 129 (100), 31 (100). Anal. calcd for C H N O
23 19 3 3
(
385.42): C, 71.67; H, 4.97; N, 10.90. Found: C, 71.82; H,
3
.2 | General procedure for preparation
5.20; N, 10.93%.
of compounds 16a–b and 17a–b
1-Ethy-5-methyl3,10a-dihydropyrazolo[4,3-a]
quinolizine-1,5-dicarboxylate (17a). Yellow powder, mp
ꢀ
ꢀ
−1
To a stirred mixture of quinoline or pyridine 15 (2 mmol)
and dimethyl acetylenedicarboxylate 2a (2 mmol) in
water (3 mL) under ultrasonic irradiation was added after
123 C-125 C, Yield: 0.67 g (95%). IR (KBr) (ν /cm ):
max
1
−
1
1739, 1737, 1697, 1586, 1464, 1296 cm . H NMR
(500 MHz, CDCl ): 1.56 (3 H, t, J = 7.4 Hz, CH ), 3.78
3
3
3

TABARSAEI ET AL.
9
3
(
3 H, s, MeO), 4.36 (2 H, q, J = 7.4 Hz, CH O), 5.45 (1 H,
3.2.2 | Evaluation of reducing ability for
synthesized compounds
2
3
d, J = 7.5 Hz, CH), 6.32 (1 H, s, CH), 6.94 (1 H, t,
J = 7.6 Hz, CH), 7.34 (1 H, t, J = 7.5 Hz, CH), 7.45 (1 H,
d, J = 7.5 Hz, CH), 7.95 (1 H, d, J = 7.5 Hz, CH), 8.52
1 H, s, NH) ppm. C NMR (125.7 MHz, CDCl ): 13.8
3
3
3
3
The ability of reducing iron (III) was evaluated for the
13
51
(
(
compounds 6a–d using Yildirim et al method. For this
3
Me), 46.3 (CH), 52.5 (MeO), 62.3 (CH O), 94.6 (CH),
purpose, the samples (1 mL), phosphate buffer (2.5 mL,
2
9
1
5.3 (CH), 108.4 (C), 115.2 (CH), 123.4 (CH), 127.5 (CH),
0.2 mol/L, pH 6.6) and potassium ferricyanide (K Fe
3
28.2 (C), 129.68 (C), 130.4 (C), 161.2 (C O), 164.3
(CN) ; 2.5 mL, 10 g/L) were combined together and
6
+
ꢀ
(C O) ppm. MS (EI, 70 eV): m/z (%) = 301 (M , 10),
sustained for 30 minutes at 50 C. Then, trichloroacetic
2
70 (84), 129 (100), 31 (100). Anal. calcd for C H N O
15 3 4
acid (2.5 mL, 10% w/v) was added to the previous solu-
tion and centrifuged for 10 minutes. In the end, the
supernatant (2.5 mL) was mixed with distilled water
15
(301.29): C, 59.79; H, 5.02; N, 13.95. Found: C, 59.96; H,
5
.24; N, 14.18%.
Methy1-(4-methoxy phenyl) 3,10a-dihydropyrazolo
(2.5 mL) and FeCl (0.5 mL, 1 g/L) and the samples
3
[
4,3-a]quinolizine-5-carboxylate (17b). Pale yellow pow-
absorbance was computed at 700 nm. The higher reduc-
ing power was attributed to higher absorbance. For accu-
racy of calculating, each calculation was performed in
three times. The SPSS software version 18.0 was used for
data analysis of compounds by running one way analysis
of variance (ANOVA) that confirmed variation in the
mean value of samples and control. All removing were
done by Duncan multiple range tests employing the
importance level of 95% (P < .05).
ꢀ
ꢀ
der, mp 138 C-140 C, Yield: 0.55 g (92%). IR (KBr)
−
1
−1 1
(
(
νmax/cm ): 1743, 1698, 1586, 1488, 1296 cm . H NMR
500 MHz, CDCl ): 3.78 (3 H, s, MeO), 3.83 (3 H, s,
3
3
MeO), 4.86 (1 H, d, J = 6.8 Hz, CH), 6.42 (1 H, s, CH),
6
3
3
.87 (1 H, t, J = 7.5 Hz, CH), 7.05 (1 H, t, J = 7.5 Hz,
3
CH), 7.16 (1 H, d, J = 7.5 Hz, CH), 7.22 (2 H, d,
3
3
J = 7.6 Hz, 2 CH), 7.64 (2 H, d, J = 7.6 Hz, 2 CH), 8.07
3
13
(1 H, d, J = 7.6 Hz, CH), 8.45 (1 H, s, NH) ppm.
C
NMR (125.7 MHz, CDCl ): 48.6 (CH), 52.3 (MeO), 55.2
3
(MeO), 94.2 (CH), 97.5 (CH), 112.3 (C), 113.5 (2 CH),
ACKNOWLEDGMENTS
1
14.2 (CH), 122.5 (CH), 126.8 (2 CH), 127.5 (CH), 128.2
We gratefully acknowledge for supporting from the
Islamic Azad University of Gorgan and Qaemshahr.
(
(
C), 129.5 (C), 130.7 (C), 143.2 (C), 158.4 (C), 162.5
C O) ppm. MS (EI, 70 eV): m/z (%) = 335 (M , 15),
+
3
04 (86), 129 (100), 31 (100). Anal. calcd for C H N O
17 3 3
ORCID
19
(
5
335.36): C, 68.05; H, 5.11; N, 12.53. Found: C, 68.23; H,
.32; N, 12.74%.
Navisa Tabarsaei https://orcid.org/0000-0002-3964-
583X
Naghmeh Faal Hamedani https://orcid.org/0000-0002-
6043-7963
3
.2.1 | Determination of antioxidant
Zinatossadat Hossaini https://orcid.org/0000-0001-
7193-1759
activity using radical trapping test
by (DPPH)
REFERENCES
The radical trapping experiment by DPPH was
employed for valuation of antioxidant ability for some
generated compounds such as 6a–d as indicated by
[1] Y. Q. Liu, L. H. Li, L. Yang, H. Y. Li, Chem Pap 2010, 64, 533.
[2] M. Meciarova, V. Polackova, S. Toma, Chem Pap 2002,
56, 208.
5
0
[3] M. Meciarova, S. Toma, P. Babiak, Chem Pap 2004, 58, 104.
Shimada et al procedure. For achieving to this pur-
pose, different concentrations (200-1000 ppm) of com-
pounds 6a–d were added to DPPH methanolic solution
[
[
[
4] K. Tabatabaeian, M. Mamaghani, N. O. Mahmoodi,
A. Khorshidi, Catal Commun 2008, 9, 416.
5] M. Meciarova, S. Toma, J. L. Luche, Ultrason. Sonochem. 2001,
(
1 mmol/L) with an equal volume. The mixtures were
8, 119.
mixed for 30 minutes at ambient temperature and after
this time computed in a dark room. Then, the mixture
absorbance was calculated and recorded at 517 nm.
The compounds 6a–d were exchanged with methanol
6] M. Vinatoru, E. Bartha, F. Badea, J. L. Luche, Ultrason.
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