Synthesis and structural characterization of novel O-substituted phenolic and chalcone derivatives with antioxidant activity

Article abstract of DOI:10.1177/1747519820932789

A series of novel 4-O-alkyltriazolylphenolic derivatives is first synthesized with good to excellent yields via the click reaction of 3-methoxy-4-O-propargylbenzaldehyde or 3-allyl-4-O-propargylacetophenone and aromatic azide derivatives. Next, the chalco

Full text of DOI:10.1177/1747519820932789

9
research-arti
3cle2020 2789CHL0010.1177/1747519820932789Journal of Chemical ResearchNgameni et al.
Research Paper
Journal of Chemical Research
–8
1
Synthesis and structural characterization
of novel O-substituted phenolic and chalcone
derivatives with antioxidant activity
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1
,2
3
4
Bathélémy Ngameni
, Musa Erdoğan , Victor Kuete ,
2
5
2
Erdin Dalkılıç , Bonaventure T Ngadjui and Arif Daştan
Abstract
A series of novel 4-O-alkyltriazolylphenolic derivatives is first synthesized with good to excellent yields via the click
reaction of 3-methoxy-4-O-propargylbenzaldehyde or 3-allyl-4-O-propargylacetophenone and aromatic azide derivatives.
Next, the chalcones are prepared via the Claisen-Schmidt method from 4-O-alkylphenylketone derivatives in the
presence of the corresponding (hetero)aromatic aldehydes as electrophiles. The structures of the newly synthesized
compounds are confirmed from their infrared, nuclear magnetic resonance spectral data, and by elemental analysis. The
main advantages of this procedure are the simplicity of the reaction conditions, easily available starting materials, and
simple work-up. The antioxidant activity of several of the products is determined using the DPPH (2,2-diphenyl-1-picryl-
hydrazyl-hydrate) radical scavenging assay. 4-O-propargylvanillin (IC =14.54µg/mL) had moderate antioxidant activity.
5
0
Keywords
,3-dipolar cycloaddition, antioxidant activity, click chemistry, condensation reaction, O-alkylation, triazolated derivatives
1
Date received: 11 February 2020; accepted: 15 May 2020
The antioxidant activity of novel 4-O-alkyltriazolylphenylaldehydes/ketones, O-substituted triazolyl-chalcone derivatives,
and vitamin C was determined using DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) radical scavenging assay. Some of these
synthesized molecules had moderate antioxidant activities meanwhile other compounds displayed low antioxidant capacity.
N
N
N
N
N
Ea
ig
N
N
N
N
s
y
y
H
O
h
sy
ld
s
O
O
n
ie th
esi
N
O
s
O
1
OH
O
O
O
2
a
3a
O
O
3b
N
N
O
O
N
N
N
N
N
N
N
N
N
O
O
O
O
O
Cl
F
F
4a
Cl
4b
N
4c
F
OH
O
O
O
N
N
N
2
N
N
N
N
N
O
O
4
d
4e Cl
s
d
un
t
Cl
n
ida
o
x
p
tio
e
m
o
n
c
A
Chalcone and Click
hybrid cores
ctiv
a
1Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty
of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Bathélémy Ngameni, Department of Pharmacognosy and Pharmaceutical
Corresponding authors:
Cameroon
Chemistry, Faculty of Medicine and Biomedical Sciences, University of
Yaoundé I, P.O. box 1364, Yaoundé, Cameroon.
Email: bath_ngameni@yahoo.fr
2
3
4
5
Department of Chemistry, Faculty of Science, Ataturk University,
Erzurum, Turkey
Department of Food Engineering, Faculty of Engineering and
Architecture, Kafkas University, Kars, Turkey
Department of Biochemistry, Faculty of Science, University of Dschang,
Dschang, Cameroon
Arif Daştan, Department of Chemistry, Faculty of Science, Ataturk
University, 25240 Erzurum, Turkey.
Email: adastan@atauni.edu.tr
Department of Organic Chemistry, Faculty of Science, University of
Yaoundé I, Yaoundé, Cameroon

2
Journal of Chemical Research 00(0)
Introduction
phenolic and chalcone derivatives are an important class of
compounds which are known to possess good biological
activities.
The synthetic routes to the desired compounds are out-
lined in Schemes 1–3. Initially, 4-O-substituted phenolic
derivatives 1a–c were used as the starting materials, and
were prepared via two precursors 1 and 1-(3-allyl-4-hy-
droxyphenyl)ethanone (2). Compounds 1a–c were synthe-
Chalcones (1,3-diphenyl-2-propen-1-ones) and their deriv-
atives are an important class of natural products. They are
found in a large number of plants and are considered to be
precursors or intermediates in flavonoid and isoflavonoid
synthetic pathways. Chalcones are also useful compounds
in pharmaceutical chemistry. Notably, chalcones and their
derivatives have been found to be associated with various
biological activities. Our previous research on this class
of molecules indicated that many natural and synthetic
chalcones exhibit a wide spectrum of biological activities,
1
sized by a one-pot nucleophilic substitution reaction as
2
6,21
described in the literature.
The acetophenone 1c was
obtained in a good 84% yield (Scheme 1).
Azide derivatives 3–5, for use in this work for 1,3-dipo-
lar cycloaddition (click reaction) were prepared using pre-
3
4
5
such as antimalarial, antimicrobial, antifungal, and anti-
6
,7
tumour activity.
22–24
viously described methods (Scheme 2).
Recent work has explored the introduction of an alkyl-
triazolyl group in the chalcone skeleton at the C-4 position
to afford lead compounds for the development of new ther-
The intermediates, 4-O-methyltriazolylphenylaldehyde
2
a and ketones 3a,b, were prepared in very good yields by
the click reaction with aromatic azides 3–5 and the corre-
sponding 4-O-propargylphenolic derivatives 1b,c at ambi-
ent temperature in the presence of CuSO ·5H O (2mol%)
8
apeutic agents. Chalcones substituted with imidazoles,
9
10
11
triazoles, amines, and stilbene have been reported to be
potential antimalarial compounds. They have also been
used as the synthetic intermediates of choice for function-
alization of the α,β-position during the total synthesis of
natural products such as the tropone-chalcones and hetero-
cyclic derivatives which have attracted considerable inter-
4
2
and (+)-sodium l-ascorbate (5mol%) in a mixture of
2
5,26
t-BuOH/H O (1:1) (Scheme 2).
This synthesis of
2
O-substituted triazolyl-chalcone derivatives by the click
reaction followed the methods recently reported by Anand
2
7
28
et al. and Lv et al.
1
2
est due to their unique structure and properties. The
derivatives of 4-O-alkyltriazolylchalcone are known to
possess antibacterial and antifungal activities. The inter-
est of researchers in lead molecules containing the 1,2,3-tri-
azole group as chemotherapeutic agents for various types
of diseases is growing because they are known to exhibit a
Biologically, pyrroles tend to construct the key structure
of porphyrin rings, which act as an active moiety in chloro-
1
3
14
2
9
phyll, vitamin B12, or bile pigments. Pyrrole and its
derivatives are widely used as intermediates in synthesis of
pharmaceuticals, agrochemicals, dyes, photographic chem-
icals, perfumes, and other organic compounds. They are
also the versatile molecules, which are active against the
various diseases as antiviral, anticonvulsant, and antiin-
1
5
wide range of biological activity, such as antibiotic, anti-
1
6
17
fungal, and anticancer properties. Some 1,2,3-triazoles
are used as deoxyribose nucleic acid (DNA) cleaving
2
9
1
8
19
flammatory. Otherwise, pyrrole and its derivatives exhibit
wide range of biological activities such as anticancer and
agents and potassium channel activators. Clinically
used drugs containing a 1,2,3-triazole moiety include the
β-lactam antibiotics tazobactam and cefatrizine, as well as the
calcium channel blocker carboxyamidotriazole (Figure 1).
Also, they have been widely used as synthetic intermediates
and in industrial applications, for example, as dyes, anticor-
rosive agents, photostabilizers, photographic materials, and
3
0
antioxidant activity. In addition, the pyrrole-containing
heterocyclic compounds have attracted attention particu-
2
9
larly as antimicrobial agents. These studies confirmed
that pyrrole ring is a good pharmacophore group for the
2
9,30
design of bioactive molecules.
20
Thus, under these biological interests of pyrrole deriva-
tives, our group recently developed a synthetic methodol-
ogy of O-alkyl substituted heterocyclic-chalcones and
agrochemicals. Therefore, the biological importance of the
,2,3-triazole system as a link between two active molecules
is useful to improve their biological properties.
1
Prompted by these observations on the pharmacologi- evaluated their antioxidant profile.
cal significance of triazole derivatives, and in order to
Compounds 4a–e were prepared via the Claisen-Schmidt
discover new intermediates for the synthesis of antioxi- condensation using the appropriate substituted ketones and
3
1–34
dant agents, this research describes the synthesis of new aldehydes (Scheme 3).
All the reactions were per-
O-alkyltriazolylphenylaldehyde/ketone and chalcone formed in the presence of both KOH and EtOH. The
derivatives. The preparation of new triazolated com- obtained products were the trans chalcones, as was evident
6
,7
pounds as synthetic intermediates, is currently under from their coupling constants. The presence of the
1
investigation in our laboratory for the investigation of 1,2,3–triazole group was indicated by a singlet in the H
their potential pharmacological activities.
NMR spectra at approximately 7.60ppm, and signals for
the triazolyl C-4 and C-5 atoms at approximately 144 and
1
3
21,35
1
32ppm, respectively, in the C NMR spectra.
The
Results and discussion
structures of all the target compounds were assigned by
elemental mass analysis and by infrared (IR) and nuclear
magnetic resonance (NMR) spectroscopy.
Chemistry
The goal of our synthesis was to introduce a propargyl and
thus triazole group to 3-methoxy-4-hydroxybenzaldehyde
or 3-allyl-4-hydroxyacetophenone derivatives in order to
Biological studies
prepare the desired O-substituted chalcone moieties and to The antioxidant activity of compounds 1b, 1c, 2a, 3a, 3b,
investigate their antioxidant profiles. O-Substituted 4a, 4b, 4c, 4d, 4e, and vitamin C (reference antioxidant

Ngameni et al.
3
HO
O
N
O
HN
N
N
Cl
O
H
O
O
S
N
S
H N
N
N
N
N
2
O
N
N
OH
O
S
N
H
Cl
Cl
O
OH
H N
2
O
H N
2
Tazobactam
Cefatrizine
Carboxyamidotriazole
Figure 1. A few biologically active compounds containing 1,2,3-triazole moiety.
O
O
1
O
O
O
OH
a
b
O
O
O
1
a
Br
Br
1b
OH
O
c
O
O
2
1c
Br
Scheme 1. Synthesis of 4-O-substituted phenolic derivatives 1a–c. (a) K CO , dry acetone, reflux (65°C), 20h, N , 81%. (b) K CO ,
2
3
2
2
3
dry acetone, reflux (65°C), 16h, N , 92%. (c) K CO , dry acetone, reflux (69°C), 16h, N , 84%.
2
2
3
2
N3
O
O
O
b
O
3
a
N
N
N
O
O
1
2
a
O
O
c
N
b
O
N
N
N
O
N
N
O
N
3
N3
N
O
N
4
1c
3b
5
3a
Scheme 2. Synthesis of O-substituted 4-O-methyltriazolylphenylaldehyde 2a and ketones 3a,b via the click reaction. (a)
CuSO ·5H O, (+)-Sodium ꢀ-ascorbate, t-BuOH/H O (1:1), room temperature, 16h, 88%. (b) CuSO ·5H O, (+)-Sodium ꢀ-
4
2
2
4
2
ascorbate, t-BuOH/H O (1:1), room temperature, 26h, 71%. (c) CuSO ·5H O, (+)-Sodium ꢀ-ascorbate, t-BuOH/H O (1:1), room
2
4
2
2
temperature, 15h, 86%.
molecule) were determined using the DPPH (2,2-diphenyl has moderate antioxidant activity meanwhile all the other
-
(
1-picryl-hydrazyl-hydrate) radical scavenging assay compounds displayed low antioxidant capacity. The
Table 1). recorded IC values were however below 52µg/mL. At the
Chemicals are considered to have high or significant anti- highest concentration of 1000µg/mL, all the compounds
oxidant capacity when their IC value is below 10μg/mL, displayed more than 70% DPPH scavenging activity, with
5
0
5
0
moderate antioxidant capacity for IC50 values between 10 even more than 90% for compounds 1b (95.03%), 3a
and 20μg/mL and low antioxidant capacity if the IC value (91.43%), and 4e (91.48%) along with vitamin C (98.78%)
5
0
3
6
is >20μg/mL. Thus, compound 1b (IC =14.54µg/mL) (Table 1). The fact that the DPPH radical scavenging
0

4
Journal of Chemical Research 00(0)
O
N
N
N
O
O
O
4a
O
O
a
O
O
1a
O
N
N
b
N
N
N
N
N
O
N
O
N
d
Cl
Cl
N
O
O
N
Cl
4c
O
O
N
3a
F
F
F
N
Cl
F
4b
c
N
F
F
O
O
N
N
N
N
O
4d
O
N
O
O
N
N
N
N
N
e
N
+
N
O
O
N
Cl
Cl
N
Cl
4e
3b
Cl
Scheme 3. Synthesis of 4-O-methyltriazolyl-chalcone derivatives 4a–e. (a) KOH (aq.) (50%), EtOH, 40°C, 45h, N , 90%. (b) KOH
2
(
aq.) (50%), EtOH, 42°C, 80h, N , 88%. (c) KOH (aq.) (50%), EtOH, 42°C, 45h, N , 68%. (d) KOH (aq.) (50%), EtOH, 42°C, 39h,
2
2
N , 80%. (e) KOH (aq.) (50%), EtOH, 40°C, 45h, N , 90%.
2
2
Table 1. Antioxidant activity of the prepared compounds and
vitamin C as determined by the DPPH radical scavenging assay.
Conclusion
In conclusion, we have developed an efficient method for
the synthesis of new O-substituted triazolylphenylalde-
hyde/ketone compounds as interesting intermediates for the
preparation of chalcone derivatives in order to explore
their antioxidant profiles. Also, this synthesis, which will
be the key subject of our further research, offers significant
improvements over existing procedures and thus helps to
facilitate the synthesis of a variety of O-alkyltriazole com-
pounds with potentially high synthetic and biological utili-
ties. Further studies on O-substituted phenolic and chalcone
derivatives as model intermediates for the synthesis of anti-
oxidant lead compounds are currently under investigation
in our laboratory.
Sample
Inhibition percentage
at 1000µg/mL
IC50 values
in µg/mL
1
1
2
3
3
4
4
4
4
4
b
c
95.03±1.90
88.79±3.12
88.75±1.76
91.43±2.09
86.85±4.27
71.24±3.18
85.12±2.09
85.12±4.87
89.10±3.63
91.48±3.26
98.78±0.89
14.54±1.71 A
24.74±3.17 B, C
36.01±2.45 D
20.25±1.09 B
42.68±2.98 E
45.98±2.39 E, F
27.83±2.55 C
51.25±3.11 F
50.88±2.82 F
22.11±1.77 B
12.64±0.91 A
a
a
b
a
b
c
d
e
Vitamin C
Values are mean±standard deviation (SD) of six independent
Experimental section
General
experiments; values with the same letter are not significantly different
(p<0.05; ANOVA).
Melting points were determined using open-glass capillar-
capacity of 1b is closer to that of the reference compound, ies on a Gallenkamp 8093/08/224 melting point apparatus
vitamin C, suggests that this compound can be used as anti- which are uncorrected. IR spectra were determined with a
oxidant agent.
Perkin Elmer FT-IR spectrophotometer. Nuclear magnetic

Ngameni et al.
5
resonance (NMR) spectra were recorded using a Bruker or 1-(3-allyl-4-propargyloxyphenyl)ethanone
(1c): White
1
Varian spectrometers (400MHz for H NMR and 100MHz solid; m.p. 47–48°C; yield 84%; R =0.19; (hexane-EtOAc
f
1
3
for C NMR). The chemical shifts are reported in parts per 9:1 v/v); IR (CHCl ): 3962, 3502, 3293, 3078, 2920, 2579,
3
million (ppm) downfield from tetramethylsilane (TMS), 2122, 2039, 1846, 1682, 1639, 1600,1496, 1454, 1424,
which was used as the internal standard. Elemental analyses 1360, 1318, 1267, 1190, 1132,1077, 1023, 979, 924, 814,
−
1
1
were recorded on a LECO 932 CHNS elemental analyzer. 682, 657, 595, 579cm ; H NMR (400MHz, CDCl ): δ
3
Thin-layer chromatography (TLC) was carried out using 7.85 (dd, J=8.6, 2.0Hz, 1H), 7.80 (d, J=2.0Hz, 1H), 7.00
Merck silica gel 60 F-254 plates (layer thickness=0.25 mm), (d, J=8.6Hz, 1H), 6.06–5.86 (m, 1H), 5.10–5.06 (m, 2H),
and all solvents were distilled prior to use.
4.78 (d, J=2.1Hz, 2H), 3.42 (br d, J=6.6Hz, 2H), 2.55–
1
3
All the azide derivates 3–5 were synthesized according 2.54 (m, 4H); C NMR (100MHz, CDCl ): δ 197.0, 159.1,
3
2
2–24
to a previously reported method.
135.9, 130.8, 130.4, 129.4, 128.6, 116.2, 111.1, 78.0, 76.0,
5
6
6.0, 34.2, 26.4; Anal. Calcd for C H O : C, 78.48; H,
.59; found: C, 78.52; H, 6.62%.
14 14 2
General procedure for the synthesis of
-allyloxy-3-methoxybenzaldehyde (1a)
4
3
-Azidopyridine (4)
To vanillin (1) (1.95g, 12.82mmol) in dry acetone (25mL)
(2.00g, 21.2mmol) was dissolved in a solution of conc.
was added K CO (1.77g, 12.82mmol) followed by allyl
2
3
H SO (2.4mL) and H O (14mL). The resulting solution
was cooled to 0°C, and a solution of NaNO (1.76g,
2
ring. The solution was stirred at this temperature for a fur-
ther 15 min, whereupon a solution of NaN3 (2.34g,
3
ring. The mixture was stirred for 1h at 0°C, then overnight
at room temperature. The reaction mixture was basified
with freshly saturated Na CO solution and extracted with
bromide (1.12mL, 1.55g, 12.82mmol). The reaction mix-
ture was refluxed for 20h at 65°C under a nitrogen atmos-
phere. The progress of the reaction was monitored by TLC.
On completion of the reaction, the solvent was removed
under reduced pressure and the residue was diluted in cold
water (50mL). The aqueous mixture was extracted with
EtOAc (3×100mL) and the combined extract was dried
over anhydrous Na SO . After evaporation of the solvent
2
4
2
2
5.6mmol) in H O (10mL) was added dropwise with stir-
2
6.0mmol) in H O (8mL) was added with vigorous stir-
2
2
4
and purification by column chromatography on silica gel
2
3
CH Cl (3×30mL). The combined extracts were washed
with H O (50mL), dried over MgSO , and the solvent
removed in vacuo to provide 3-azidopyridine (4) (1.92g,
eluting with hexane-EtOAc of increasing polarity, product
2
2
6
1
a was obtained as a colorless oil (2.00g, yield 81% in
2
4
hexane-EtOAc 85:15).
7
5%), which was used in the next step without additional
2
3
purification.
General procedure for the synthesis of
3
-methoxy-4-O-propargylbenzaldehyde (1b)
General procedure for the synthesis of the
and 3-allyl-4-O-propargylacetophenone (1c)
4
-O-methyltriazolylphenylaldehyde/ketone
To a stirring mixture of vanillin (1) (2.030g, 13.34mmol)
or 1-(3-allyl-4-hydroxy)ethanone (2) (2.030g, 11.52mmol)
and anhydrous K CO (3.180 g, 23.01 mmol, 2.00 equiv.)
derivatives 2a, and 3a–b
A mixture of 3-methoxy-4-O-propargylbenzaldehyde (1b)
or 3-allyl-4-O-propargylacetophenone (1c) (0.582g,
2
3
in dry acetone (20mL), propargyl bromide (1.30mL,
.800g, 12.10mmol) was slowly added at ambient temper-
ature. The reaction mixture was refluxed (65–69°C) for
6h under a nitrogen atmosphere. After completion of the
3
3
0
0
.06mmol, 1.00 equiv.), azide derivative 3 or 4, 5, (0.625g,
.69mmol, 1.10 equiv.), CuSO ·5H O (0.267g, 1.07mmol,
1
4
2
.35 equiv.) and sodium ascorbate (0.133g, 0.67mmol,
.20 equiv.) was charged with freshly prepared solution of
1
reaction, the solvent was evaporated under reduced pres-
sure and the residue was diluted with water (40mL). The
aqueous mixture was extracted with EtOAc (3×70mL)
and the extract was dried over anhydrous Na SO . After
evaporation of the solvent under reduced pressure, the
crude product was purified by column chromatography on
silica gel eluting with hexane-EtOAc of increasing polarity
to give product 1b (2.3g, 92% in hexane-EtOAc 17:3) or 1c
t-BuOH/H O (1:1; 10mL). The heterogeneous mixture was
2
stirred vigorously for 15–26h at room temperature. The
progress of reaction was monitored by TLC, using a mix-
ture of hexane-EtOAc 7:3. After completion of the reaction,
the mixture was poured into brine or NH Cl solution and
extracted with EtOAc (3×40mL). The organic layer was
washed with cold water, dried over anhydrous Na SO , fil-
2
4
4
2
4
tered and evaporated under reduced pressure to afford a
crude product. This was purified by column chromatogra-
phy on silica gel using hexane-EtOAc mixture of increas-
ing gradient to give 2a, 3a, or 3b.
(
2.1g, 84% in hexane-EtOAc 47:3), respectively.
3
-Methoxy-4-prop-2-ynyloxy-benzaldehyde (1b):. White
solid; m.p. 85–87°C (lit.9 86°C); yield 92%,;R =0.40;
f
1
(
hexane-EtOAc 4:1 v/v); H NMR (400MHz, CDCl ): δ
3
9
.87 (s, 1H), 7.47 (br d, J=8.2Hz, 1H), 7.44 (br s, 1H), 7.15 3-Methoxy-4-[{1-(naphthalen-1-yl)-1H-1,2,3-triazol-4-yl}
(
d, J=8.2Hz, 1H), 4.86 (d, J=1.8Hz, 2H), 3.94 (s, 3H), methoxy]benzaldehyde (2a): Colorless solid; m.p. 127–
1
3
2
1
5
.58 (t, J=1.8Hz, 1H); C NMR (100MHz, CDCl ): δ 128°C; yield 88%; R =0.22; (hexane-EtOAc 7:3 v/v); IR
3
f
91.0, 152.3, 150.2, 131.1, 126.3, 112.8, 109.7, 77.7, 76.9, (CHCl ): 3143, 3060, 2939, 2834, 1681, 1587, 1508, 1465,
3
6.8, 56.2.
1425, 1388, 1339, 1267, 1235, 1159, 1136, 1043, 1019,

6
Journal of Chemical Research 00(0)
−1
1
−1 1
9
99, 951, 864, 802, 773, 731, 701, 643, 591, 571cm ; H 1032, 997, 923, 804, 725, 554 cm ; H NMR (400MHz,
NMR (400MHz, CDCl ): δ 9.86 (s, 1H), 8.07 (s, 1H), CDCl ): δ 8.03 (dd, J=8.6, 2.2Hz, 1H), 7.97 (d, J=2.2Hz,
3
3
8
.03–7.86 (m, 2H), 7.77–7.38 (m, 7H), 7.33 (s, 1H), 5.53 1H), 7.85 (d, J=15.6Hz, 1H), 7.64 (s, 1H), 7.54–7.50 (m,
1
3
(
s, 2H), 3.92 (s, 3H); C NMR (100MHz, CDCl ): δ 190.9, 1H), 7.50–7.45 (m, 3H), 7.45–7.34 (m, 2H), 7.32–7.23 (m,
3
1
1
1
7
1
53.0, 150.0, 143.2, 134.1, 133.5, 130.9, 130.8, 128.6, 2H), 7.17 (d, J=8.6Hz, 1H), 7.01 (d, J=8.3Hz, 1H), 6.20
28.5, 128.0, 127.1, 126.7, 125.9, 125.0, 123.6, 122.2, (ddd, J=20.4, 10.6, 5.4Hz, 1H), 6.05 (ddt, J=18.2, 9.5,
12.8, 109.4, 63.0, 56.0; Anal. Calcd for C H N O : C, 6.6Hz, 1H), 5.65 (s, 2H), 5.54 (dd, J=20.4, 1.1Hz, 1H),
2
1
17
3
3
0.18; H, 4.77; N, 11.69; found: C, 70.51; H, 4.67; N, 5.43 (dd, J=10.6, 1.1Hz, 1H), 5.40 (s, 2H), 5.12 (br d,
1.42%. J=0.9Hz, 1H), 5.10–5.08 (m, 1H), 4.78 (d, J=5.4Hz, 2H),
1
3
4
.06 (s, 3H), 3.51 (d, J=6.6Hz, 2H); C NMR (100MHz,
1
-[3-allyl-4-{(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy}phe- CDCl ): δ 188.9, 159.6, 150.3, 149.6, 144.2, 144.1, 136.2,
3
nyl]ethanone (3a): White solid; m.p. 100–102°C; yield 134.4, 132.8, 131.6, 130.6, 129.2 (2C), 129.1, 128.9, 128.8,
8
3
1
7
7
5
1
2
1
6%; R =0.41; (hexane-EtOAc 2:3 v/v); IR (CHCl ): 3137, 128.3, 128.1 (2C), 122.7, 122.6, 120.0, 118.4, 116.0, 113.0,
f
3
064, 2913, 2846, 1673, 1599, 1498, 1425, 1358, 1263, 111.1, 110.7, 69.8, 62.4, 56.1, 54.3, 34.4; Anal. Calcd for
−
1 1
131, 1002, 816, 736 cm ; H NMR (400MHz, CDCl ): δ C H N O : C, 73.68; H, 5.99; N, 8.06; found: C, 73.44; H,
3
32 31
3
4
.83 (d, J=8.6Hz, 1H), 7.78 (s, 1H), 7.50 (s, 1H), 7.39– 5.93; N, 7.74%.
.37 (m, 3H), 7.32–7.24 (m, 2H), 7.02 (d, J=8.6Hz, 1H),
.96–5.86 (m, 1H), 5.54 (s, 2H), 5.27 (s, 2H), 5.00 (br s, (E)-1-(3-allyl-4-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)
H), 4.97 (br d, J=8.4Hz, 1H), 3.37 (d, J=6.5Hz, 2H), phenyl)-3-(1-(3,5-dichlorophenyl)-1H-pyrrol-2-yl)prop-2-
1
3
.54 (s, 3H). C NMR (100MHz, CDCl ): δ 197.0, 159.8, en-1-one (4b): Pale brown solid; m.p. 128–130°C; yield
3
44.2, 136.1, 134.4, 130.6, 130.3, 129.2, 129.0 (2C), 128.9 88%; R =0.26; (hexane-EtOAc 7:3 v/v); IR (CHCl ): 3476,
f
3
(
2C), 128.8, 128.1, 122.6, 116.1, 110.9, 62.4, 54.3, 34.4, 3069, 1650, 1600, 1589, 1573, 1497, 1464, 1433, 1354,
2
1
6.4; Anal. Calcd for C H N O : C, 72.60; H, 6.09; N, 1320, 1272, 1252, 1136, 1049, 1003, 917, 858, 807, 725,
21 21 3 2
−1
1
2.10; found: C, 72.65; H, 5.79; N, 11.95%.
681, 575 cm ; H NMR (400MHz, CDCl ): δ 7.83 (dd,
3
J=8.6, 2.2Hz, 1H), 7.76 (d, J=2.2Hz, 1H), 7.52 (d,
1
-[3-allyl-4-{(1-(pyridin-3-yl)-1H-1,2,3-triazol-4-yl) J=15.3Hz, 1H), 7.50 (br s, 1H), 7.43 (br t, J=1.8Hz, 1H),
methoxy}phenyl]ethanone (3b): White solid; m.p. 97– 7.38–7.37 (m, 1H), 7.36 (d, J=1.8Hz, 2H), 7.31–7.24 (m,
8°C; yield 71%; R =0.22; (hexane-EtOAc 2:3 v/v); IR 4H), 7.21 (d, J=15.3Hz, 1H), 7.03 (d, J=8.6Hz, 1H),
9
f
(
1
CHCl ): 3417, 3137, 3076, 3008, 1673, 1598, 1498, 1359, 6.98–6.92 (m, 2H), 6.41–6.38 (m, 1H), 5.91 (ddt, J=17.5,
3
−
1
1
263, 1248, 1130, 1018, 806 cm ; H NMR (400MHz, 11.0, 6.6Hz, 1H), 5.53 (s, 2H), 5.27 (s, 2H), 4.99 (br s, 1H),
1
3
CDCl ): δ 8.99 (br s, 1H), 8.68 (d, J=4.6Hz, 1H), 8.13 (br 4.98–4.94 (m, 1H), 3.37 (d, J=6.6Hz, 2H); C NMR
3
s, 1H), 8.11–8.10 (m, 1H), 7.82 (dd, J=8.6, 2.1Hz, 1H), (100MHz, CDCl ): δ 188.4, 159.8, 144.5, 141.0, 136.4,
3
7
.76 (d, J=2.1Hz, 1H), 7.48 (dd, J=8.2, 4.6Hz, 1H), 7.04 136.0 (2C), 134.7, 131.7, 130.9, 130.7, 129.4 (2C), 129.3,
(
d, J=8.6Hz, 1H), 5.94 (ddt, J=16.8, 10.7, 6.6Hz, 1H), 129.1, 128.9 (2C), 128.6, 128.3, 127.2, 125.3, 122.8, 118.9
5
1
.36 (s, 2H), 5.06–5.03 (m, 1H), 5.01 (dd, J=10.7, 1.5Hz, (2C), 116.2 (2C), 113.9, 111.7, 111.3, 62.6, 54.5, 34.7;
1
3
H), 3.39 (d, J=6.6Hz, 2H), 2.51 (s, 3H); C NMR Anal. Calcd for C H Cl N O : C, 67.49; H, 4.60; N, 9.84;
3
2
26
2
4
2
(
100MHz, CDCl ): δ 197.2, 159.8, 150.4, 145.3, 141.8, found: C, 67.35; H, 4.63; N, 9.61%.
3
1
1
36.2, 133.7, 130.9, 130.7, 129.3, 129.2, 128.4, 124.5,
21.1, 116.4, 111.1, 62.3, 34.5, 26.6; Anal. Calcd for (E)-1-(3-allyl-4-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)
C H N O : C, 68.25; H, 5.43; N, 16.76; found: C, 68.58; phenyl)-3-(1-(4-(trifluoromethyl)phenyl)-1H-pyrrol-2-yl)
1
9
18
4
2
H, 5.44; N, 16.33%.
prop-2-en-1-one (4c): Pale yellow solid; m.p. 140–142°C;
yield 80%; R =0.17; (hexane-EtOAc 7:3 v/v); IR (CHCl ):
f
3
3
1
8
098, 3068, 2936, 1650, 1600, 1536, 1498, 1454, 1357,
326, 1299, 1249, 1170, 1129, 1067, 1036, 1003, 918, 888,
50, 818, 728, 629, 604, 460 cm ; H NMR (400MHz,
General procedure for the synthesis of 4-O-
methyltriazolyl-chalcone derivatives 4a–e
−1
1
A solution of KOH (0.5g, 7.24mmol) in H O (5mL) was CDCl ): δ 7.82 (dd, J=8.6, 2.2Hz, 1H), 7.78 (d, J=2.2Hz,
2
3
slowly added dropwise to a mixture of substituted aryl/ 1H), 7.76 (d, J=3.6Hz, 2H), 7.58 (d, J=15.4Hz, 1H), 7.50
heteroaryl-carbaldehyde (2mmol) and 3-allyl-4-O-methyl- (s, 1H), 7.46 (d, J=8.4Hz, 2H), 7.39–7.35 (m, 3H), 7.28 (br
triazolyl-acetophenone (2 mmol) dissolved in EtOH (10– d, J=2.5Hz, 1H), 7.24 (d, J=15.4Hz, 1H), 7.03 (d,
2
3
0mL). The reaction mixture was stirred at 40–42°C for J=3.6Hz, 2H), 7.02 (d, J=8.6Hz, 1H), 6.98 (dd, J=3.7,
9–80h, under a nitrogen atmosphere and monitored by 1.4Hz, 1H), 6.43 (dd, J=3.7, 3.1Hz, 1H), 5.96–5.85 (m,
TLC. The precipitate formed was filtered, dried and puri- 1H), 5.54 (s, 2H), 5.27 (s, 2H), 4.99 (br s, 1H), 4.98–4.94
1
3
fied by silica gel column chromatography using a mixture (m, 1H), 3.37 (d, J=6.5Hz, 2H); C NMR (100MHz,
hexane-EtOAc to provide 4a–e, respectively. CDCl ): δ 188.0, 159.6, 144.2, 141.9, 136.1, 134.4, 131.8,
3
1
31.5, 130.7, 130.4 (2C), 129.2 (2C), 129.1, 128.9, 128.7,
E)-1-(3-allyl-4-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy) 128.1 (2C), 126.9, 126.8, 126.6 (2C), 126.5 (q, J=272.7Hz,
phenyl)-3-(4-(allyloxy)-3-methoxyphenyl)prop-2-en-1-one CF ), 125.1, 122.5, 118.3, 116.0, 113.5, 111.4, 111.1, 62.4,
(
3
1
9
(
4a): Yellow solid; m.p. 115–117°C; yield 90%; R =0.58; 54.3, 34.4; F NMR (376MHz, CDCl ): δ −62.88 (s, 3F,
f
3
(
hexane-EtOAc 3:2 v/v); IR (CHCl ): 3137, 3070, 2937, CF ); Anal. Calcd for C H F N O : C, 69.71; H, 4.79; N,
3 3 33 27 3 4 2
1
653, 1598, 1509, 1463, 1423, 1310, 1255, 1165, 1135, 9.85; found: C, 69.32; H, 4.69; N, 9.51%.

Ngameni et al.
7
(
E)-1-(3-allyl-4-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)
phenyl)-3-(1-(p-tolyl)-1H-pyrrol-2-yl)prop-2-en-1-one
4d): Pale yellow solid; m.p. 100–101°C; yield 68%;
R =0.57; (hexane-EtOAc 13:7 v/v); IR (CHCl ): 3132,
of test sample)/Absorbance of control]×100. The IC50
value is the concentration of a sample required to scavenge
(
5
0% of the DPPH free radical and was calculated from a
38
f
3
calibration curve by linear regression. One-way analysis
of variance (ANOVA) at the 95% confidence level was
used for statistical analysis.
3
1
8
065, 2975, 2923, 2874, 1648, 1600, 1586, 1516, 1498,
455, 1359, 1326, 1309, 1248, 1136, 1038, 1003, 917,
−
1 1
24, 728, 629, 606, 570, 465 cm ; H NMR (400 MHz,
CDCl ): δ 7.80 (dd, J = 8.5, 1.9 Hz, 1H), 7.74 (d, J = 1.9 Hz,
3
Declaration of conflicting interests
1
H), 7.59 (d, J = 15.4 Hz, 1H), 7.49 (br s, 1H), 7.38–7.35
dd, J = 5.5, 4.1 Hz, 3H), 7.29–7.25 (br t, J = 6.3 Hz, 4H),
.20 (d, J = 8.2 Hz, 2H), 7.15 (d, J = 15.4 Hz, 1H), 7.00
The author(s) declare no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
(
7
(
(
d, J = 8.5 Hz, 2H), 6.93 (br d, J = 3.2 Hz, 1H), 6.38–6.35
m, 1H), 5.96–5.84 (m, 1H), 5.53 (s, 2H), 5.26 (s, 2H),
Funding
4
2
1
1
1
1
.99 (br s, 1H), 4.97–4.94 (m, 1H), 3.36 (d, J = 6.5 Hz, The author(s) disclosed receipt of the following financial support
1
3
H), 2.43 (s, 3H); C NMR (100 MHz, CDCl ): δ 188.3, for the research, authorship, and/or publication of this article: B.N.
3
and A.D. are grateful for the financial support from TÜBİTAK-
59.4, 144.3, 138.1, 136.5, 136.2, 134.4, 132.7, 131.8,
BİDEB 2221-Funding of Visiting Scientists on Sabbatical
30.8, 130.4, 130.0 (2C), 129.2 (2C), 128.9, 128.8, 128.6,
Leave Fellowship Program to the Department of Chemistry,
28.1 (2C), 127.5, 126.3 (2C), 122.5, 117.4, 115.9, 112.9,
Ataturk University, Erzurum, Turkey. The authors also thank the
11.0, 110.5, 62.4, 54.3, 34.4, 21.1; Anal. Calcd for
Department of Chemistry, Ataturk University, for the important
support with the experimental equipment.
C H N O : C, 77.02; H, 5.88; N, 10.89; found: C, 77.41;
H, 5.78; N, 10.82%.
3
3
30
4
2
ORCID iDs
(
E)-1-(3-allyl-4-((1-(pyridin-3-yl)-1H-1,2,3-triazol-4-yl)
methoxy)phenyl)-3-(1-(3,5-dichlorophenyl)-1H-pyrrol-
-yl)prop-2-en-1-one (4e): Yellow solid; m.p. 160–162°C;
yield 90%; R =0.33; (hexane-EtOAc 3:2 v/v); IR (CHCl ):
Bathélémy Ngameni
Musa Erdoğan https://orcid.org/0000-0001-6097-2862
https://orcid.org/0000-0002-6045-0981
2
f
3
−
1
3
126, 1586, 1460, 1401, 1351, 1250, 1124, 1046, 806 cm ; Supplemental material
1
H NMR (400MHz, CDCl ): δ 9.01 (d, J=2.4Hz, 1H),
3
Supplemental material for this article is available online.
8
.76–8.69 (m, 1H), 8.14 (ddd, J=8.3, 2.4, 1.5Hz, 1H), 8.10
(
1
7
br s, 1H), 7.86 (dd, J=8.6, 2.1Hz, 1H), 7.79 (d, J=2.1Hz,
H), 7.52 (d, J=15.4Hz, 1H), 7.50 (br t, J=3.9Hz, 2H),
.43 (br t, J=1.8Hz, 1H), 7.25 (d, J=1.8Hz, 1H), 7.20 (d,
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0
23
2
5
2
2
8
4
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