An efficient click synthesis of chalcones derivatized with two 1-(2-quinolon-4-yl)-1,2,3-triazoles

Article abstract of DOI:10.1515/znb-2021-0028

Chalcones derivatized with 1-(2-quinolonyl)-1,2,3-triazoles were synthesized by reaction of 4-azido-2-quinolones with 1-phenyl-3-(4-propargyloxyphenyl)prop-2-en-1-one, or by aldol reaction of 4-{[1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}benzaldehydes with acetophenone. Whereas, chalcones bearing two 1-(2-quinolonyl)-1,2,3-triazoles were synthesized by reaction of 1,3-bis(4-propargyloxyphenyl)prop-2-en-1-one with 4-azido-2-quinolones, or by aldol condensation between 4-{4-[(4-acetylphenoxy)methyl]-1H-1,2,3-triazol-1-yl}quinolin-2(1H)-ones and 4-{[1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}benzaldehydes.

Full text of DOI:10.1515/znb-2021-0028

Z. Naturforsch. 2021; 76(6–7)b: 395–403
Mohammed B. Alshammari*, Ashraf A. Aly*, Alan B. Brown, Md Afroz Bakht,
Ahmed M. Shawky, Adel M. Abdelhakem and Essmat M. El-Sheref*
An efficient click synthesis of chalcones
derivatized with two 1-(2-quinolon-4-yl)-
1,2,3-triazoles
https://doi.org/10.1515/znb-2021-0028
Received February 22, 2021; accepted June 18, 2021;
published online June 17, 2021
being clinically assayed for the treatment of cancer, cardio-
vascular diseases, and viral infections [1]. Some chalcones
have shown activity against cardiovascular disease [2] and
tumor promotion [3] since they decrease the inflammation
signaling pathways in affected cells [3]. The induction of
apoptosis by chalcones usually consists of mitochondrial
pathways, down-regulation of anti-apoptotic proteins, and/
or death receptor pathways [4–6]. Chalcones may also cause
apoptosis through generation of reactive oxygen species
(ROS) [7], despite being known as antioxidant molecules.
Strong reactivity with thiol groups in living organisms would
stimulate the pro-oxidant activity of chalcones due to the
induction of a series of reactions with hydroxyl radicals in
living cells, or by reducing the antioxidant mechanisms, such
as the glutathione content [7]. Furthermore, some chalcones
exhibited a potent renoprotective effect, when they evaluated
for any renoprotective effects on cisplatin-treated cultured
kidney cells (LLC-PK1) [8].
Abstract: Chalcones derivatized with 1-(2-quinolonyl)-
1,2,3-triazoles were synthesized by reaction of 4-azido-
2-quinolones with 1-phenyl-3-(4-propargyloxyphenyl)
prop-2-en-1-one, or by aldol reaction of 4-{[1-(2-oxo-
1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}
benzaldehydes with acetophenone. Whereas, chalcones
bearing two 1-(2-quinolonyl)-1,2,3-triazoles were syn-
thesized by reaction of 1,3-bis(4-propargyloxyphenyl)
prop-2-en-1-one with 4-azido-2-quinolones, or by aldol
condensation between 4-{4-[(4-acetylphenoxy)methyl]-
1H-1,2,3-triazol-1-yl}quinolin-2(1H)-ones and 4-{[1-(2-oxo-
1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}
benzaldehydes.
Keywords: aldol condensation; bis(2-quinolonyl)-bis-1,2,
A quinoline moiety is present in many classes of natural
products of biologically active compounds [9]. Several of
them have been clinically used as antifungal, antibacterial,
and antiprotozoic drugs [9], as well as antituberculotic
agents [10]. Some quinoline-based compounds have also
revealed antineoplastic, antiasthmatic, and antiplatelet ac-
tivity [11, 12]. A series of compounds derived from
8-hydroxyquinoline and styrylquinoline derivatives have
recently synthesized as potential HIV-1 integrase inhibitors
[13, 14].
Aly et al. reported on the promise of 3,3′-methylenebis
[4-hydroxyquinolin-2(1H)-ones] as anti-Covid-19 agents
[15]. Also a series of 6-substituted 4-[2-(4-substituted-ben-
zylidene)-hydrazinyl]quinolin-2(1H)-one derivatives was
synthesized [16]. The target compounds were evaluated for
their in vitro cytotoxic activity against 60 cancer cell lines.
The most active compounds were further examined against
the most sensitive leukemia RPMI-8226 and healthy
cell lines [16]. In addition, we reported on the synthesis
of new quinolin-2-one/pyrazole hybrids and their anti-
apoptotic activity [17].
3-triazoles; chalcones.
1 Introduction
Chalcones have found success as commercial drugs for the
treatment of some digestive system diseases and some are
*Corresponding authors: Ashraf A. Aly, Department of Chemistry,
Faculty of Science, Minia University, 61519, Minia, Egypt,
E-mail: ashrafaly63@yahoo.com; Mohammed B. Alshammari,
Chemistry Department, College of Sciences and Humanities, Prince
Sattam bin Abdulaziz University, P. O. Box 83, Al-Kharj 11942, Saudi
Arabia, E-mail: m.alshammari@psau.edu.sa; and Essmat M. El-
Sheref, Department of Chemistry, Faculty of Science, Minia University,
61519, Minia, Egypt, E-mail: essmat_elsheref@mu.edu.eg
Alan B. Brown, Chemistry Department, Florida Institute of Technology,
150 W University Blvd, Melbourne, FL 32901, USA
Md Afroz Bakht, Chemistry Department, College of Sciences and
Humanities, Prince Sattam bin Abdulaziz University, P. O. Box 83,
Al-Kharj 11942, Saudi Arabia
Ahmed M. Shawky, Science and Technology Unit (STU), Umm Al-Qura
University, Makkah 21955, Saudi Arabia,
1,2,3-Triazoles have attracted considerable interest
due to their ease of synthesis and diverse medicinal prop-
erties [18, 19]. The large dipole moment of this heterocycle
E-mail: amesmail@uqu.edu.sa
Adel M. Abdelhakem, Department of Medicinal Chemistry, Faculty of
Pharmacy, Minia University, 61519, Minia, Egypt

396
M.B. Alshammari et al.: Chalcones derivatized with quinolonyl-1,2,3-triazoles
imparts to it hydrogen bond–forming ability which could
All products 7a–d were formed by combination of
sometimes be desirable for better binding into the cavities 4-azido-2-quinolinones 1a–d with chalcone 6a in the
of biomolecules [20]. The 1,2,3-triazole moiety is exten- molar ratio of 1:1 without any elimination. All click re-
sively used to develop libraries of compounds effective actions gave a single regioisomer, as evidenced by a
against cancer cells [21]. The aforementioned findings single set of NMR signals. The assigned structure of
encouraged us to design and synthesize five bioactive sites compound 7a, for example, appears in Figure 2; its NMR
in one molecule (Figure 1), utilizing click chemistry.
data appear in the Section 3, and the full 2D correlations
are shown in Table 1. The NMR spectra of 7a consist of two
coupling networks, joined by the triazole ring. The car-
bon atom C-a is distinctive at δC = 189.1 ppm. C-a gives
HMBC correlation to two protons with a large mutual
coupling (J = 15.5 Hz), assigned as H-b and H-c in some
order, and to a 2H doublet at δH = 8.15 ppm, assigned as
H-o. H-o gives HSQC correlation with its attached carbon
at δC = 128.4 ppm, and COSY correlation with a 2H doublet
at δH = 7.57 ppm, assigned as H-m. H-m, and H-o give
HMBC correlation with a carbon at δC = 131.9 ppm,
assigned as C-p; H-m alone gives HMBC correlation with a
carbon at δC = 137.8 ppm, assigned as C-i.
2 Results and discussion
Our synthetic protocol (Scheme 1) began with the prepa-
ration of 4-hydroxy-2-quinolinones 1a–e according to the
literature [22, 23]. 4-Hydroxy-2-quinolinones 1a–e were
treated with POCl3 to give 2,4-dichloroquinolines 2a–d and
4-chloro-2-quinolinone (2e) (R1 = Me) [24]. Compounds 2a–d
were subjected to refluxing acetic acid-water to obtain
4-chloro-2-quinolinones 3a–d [24]. Finally, either com-
pounds 2e or 3a–d were subjected to sodium azide to
produce 4-azidoquinolin-2(1H)-ones 4a–e [25].
1
The H doublets at δH = 7.84 and 7.75 ppm give HSQC
correlation with their attached carbons at δC = 119.9 and
143.8 ppm, respectively. The carbon at δC = 143.8 ppm gives
HMBC correlation with a 2H doublet at δH = 7.91 ppm,
assigned as H-o′. If one assumes this to be a three-bond
correlation, it yields the assignments of C-c (δC = 143.8 ppm),
C-b (δC = 119.9 ppm), H-c (δH = 7.75 ppm), and H-b
(δH = 7.84 ppm). Consistent with these assignments, C-b
does not correlate with any aromatic proton. H-o′ gives HSQC
correlation with its attached carbon at δC = 130.8 ppm and
COSY correlation with a 2H doublet atδH = 7.21 ppm, assigned
as H-m′. H-m′ gives HSQC correlation with its attached carbon
at δC = 115.2 ppm. The carbon at δC = 127.8 ppm is assigned as
C-i′ by analogy with compound 6b. H-o′ give HMBC correla-
tion with a carbon at δC = 160.0 ppm, assigned as C-p′. C-p′
gives HMBC correlation with a 2H singlet at δH = 5.39 ppm,
assigned as H-4a; its attached carbon resonates at
δC = 61.0 ppm. H-4a gives HMBC correlation with a carbon at
δC = 143.0 ppm, assigned as C-4. C-4 gives HMBC correlation
with a 1H singlet at δH = 8.90 ppm, assigned as H-5; its
attached carbon resonates at δC = 126.7 ppm. H-5 gives HMBC
correlation with a nitrogen at δN = 247.3 ppm, assigned as N-1.
N-1 also gives HMBC correlation with a 1H singlet at
δH = 6.86 ppm, assigned as H-8; its attached carbon appears
at δC = 117.8 ppm. H-8 also gives HMBC correlation with a
nitrogen at δN = 152.3 ppm, assigned as N-6, and with carbons
at δC = 143.6 and 114.4 ppm, assigned on chemical-shift
grounds as C-9 and C-9a, respectively.
The alkyne fragments, compounds 6a,b, were synthe-
sized in very good yields from 3-(4-hydroxyphenyl)-1-
phenylprop-2-en-1-one (5a) or 1,3-bis(4-hydroxy-phenyl)
prop-2-en-1-one (5b) with propargyl bromide (Scheme 1)
[26, 27]. Then, copper(I)-catalyzed azide-alkyne [3+2] dipolar
cycloaddition reaction (CuAAC) [28] afforded the target hy-
brids 7a–d, ingoodtoexcellentyields(Method A)depending
on the concentration of the catalyst (Scheme 2). Also, our
target compounds 7a–d were synthesized, in very good
yields, via the reaction of 4-{[1-(2-oxo-1,2-dihydroquinolin-
4-yl)-1H-1,2,3-triazol-4-yl]methoxy}benzaldehydes 8a–d [29]
with acetophenone (9) Method B (Scheme 2). All the syn-
thesized compounds were characterized using NMR spec-
troscopy (1H, 13C, and 2D), elemental analysis, and mass
spectrometry. They were in good agreement with the
assigned structures.
Assignment of the quinoline is straightforward except
for the benzene ring. Assignments in this ring follow from
an HMBC correlation between C-13a (δC = 139.4 ppm) and
H-12 (δH = 7.65 ppm).
Figure 1: General structure of chalcones derivatized with two
quinolonyl-1,2,3-triazoles.

M.B. Alshammari et al.: Chalcones derivatized with quinolonyl-1,2,3-triazoles
397
Scheme 1: Synthesis of target compounds 4a–e and alkynes 6a, b.
The regiochemical assignment of the 1,4-disubstituted- phenyl]prop-2-en-1-one (6b) and 4-azidoquinolin-2(1H)-
1,2,3-triazole ring is based on analogy with compound 8e ones 4a–d in the presence of CuAAC to obtain
(Figure 3), in which N-3 is detected; it has a distinctive 1,2,3-triazoles 10a–d in 73–81 yield (Method A). The
downfield chemical shift (δN = 358.1 ppm) – as does N-2, in 1,2,3-triazoles 10a–d were also synthesized by the re-
other compounds – and gives HMBC correlation with H-4a actions of aldehydes 8a–d with 4-{4-[(4-acetylphenoxy)-
[29]. Throughout our series of 4-(1,2,3-triazolo)quinolin- methyl]-1H-1,2,3-triazol-1-yl}-quinolin-2(1H)-ones 11a–d in
2(1H)-ones (18 compounds; ref. [29]. and current work), N-6 basic medium (Method B) as shown in Scheme 3. To
1
and N-1 resonate in the ranges δN = 152.5–146.9 and 250. confirm our results, NMR (1H, 13C, H–1H COSY, HMBC,
3–246.7 ppm, respectively.
HSQC, and 15N) in addition to elemental analysis and mass
Similarly, we prepared doubly derivatized chalcones spectrometry were performed for all the obtained products.
by interaction between (E)-1,3-bis[4-(prop-2-yn-1-yloxy) As an example of this series, we chose compound 10b

398
M.B. Alshammari et al.: Chalcones derivatized with quinolonyl-1,2,3-triazoles
Scheme 2: Reaction of 4-azido-2-quinolinones 1a–d with chalcone 6a.
the yields of products increased. We propose that due to
the reaction of CuSO4 with sodium ascorbate to form Cu+
which is responsible for reversible removal of an acidic
proton from the terminal alkyne, so during the reaction
with 5 mol% CuSO4 we would add more sodium ascorbate
to conserve the concentration of Cu+, but when we arrived
at 15 mol% of our catalyst, we found that the reaction
needed no more sodium ascorbate and went to complete-
ness in a short time (Table 3).
In summary, two new series of (1,2,3-triaz-ol-1-yl)qui-
nolin-2(1H)-ones
and
bis(4,1-phenylene)bis(oxy)bis(-
methylene)bis(1H-1,2,3-triazole-4,1-diyl)bis(N-methyl-quin-
oline-2(1H)-ones) were synthesized via onepot of click
reaction. The yields are varied from very good to excellent.
Figure 2: Assigned structure of compound 7a.
(Figure 4). The NMR data appear in the Experimental Sec-
tion; full 2D correlations are shown in Table 2. The stoi-
chiometry of one chalcone per two triazoloquinolinones
3 Experimental
1
3.1 General information
follows from H NMR integration for H-b and H-c vs the
other signals in the aromatic region, and the appearance of
two signals for H-5 and 5′, H-4a and 4a′, C-5 and 5′, C-4a
and 4a′, and C-4 and 4′. H-4a and 4a′ give HMBC correlation
with C-p and p′, respectively. The other correlations are
straightforward, and the coupling constant of 15.4 Hz be-
tween H-b and H-c shows that the chalcone C=C bond has
trans stereochemistry.
We investigated the relationship among the reaction
time, yield of products and concentration of Cu catalyst.
We found that as a result of increasing the concentration of
All reagents were used as purchased from Merck. The progress of all
reactions was monitored with thin-layer chromatography (TLC) on
Merck alumina-backed TLC plates and visualized under UV light.
Spectra were measured in DMSO-d6 on a Bruker AV-400 spectrometer
(400 MHz for 1H, 100 MHz for 13C, and 40.54 MHz for 15N) in the
Department of Chemistry, Florida Institute of Technology. 15N signals
were observed indirectly, via HSQC and HMBC experiments. Chemical
shifts are expressed in δ (ppm) versus internal tetramethylsilane (TMS;
δ = 0 ppm) for 1H and 13C, and external liquid ammonia (δ = 0 ppm) for
15N. Correlations were established using 1H–1H COSY, and 1H–13C, and
1H–15N HSQC and HMBC experiments. Splitting patterns are denoted as
Cu catalyst, the required reaction time decreased whereas follows: singlet (s), doublet (d), multiplet (m), triplet (t), quartet (q),

M.B. Alshammari et al.: Chalcones derivatized with quinolonyl-1,2,3-triazoles
399
Table : Spectral data of compound a.
3
O
N
N
N
8e

H NMR
H– H COSY Assignment
O
N
4a
. (s; H)
. (s; H)
. (d, J = .; H)
. (d, J = .; H)
. (d, J = .; H)
. (d, J = .; H)
.
.
.
.
.
.
NH
H-
H-o
H-o′
H-b
H-c
O
Figure 3: Structure of compound 8e.
. (dd, J = ., .; ., .
H)
H-
were carried out on a Perkin device at the Microanalytical Institute of
Organic Chemistry, Karlsruhe University, Germany.
. (t, J = .; H)
.
H-p
. (dd, J = ., .; ., .
H)
H-m
3.2 Starting materials
. (d, J = .; H)
. (d, J = .; H)
.
.
H-
H-
H-
4-Azidoquinolin-2(1H)-ones 4a–d were prepared according to the
literature [22–26]. (E)-1-phenyl-3-[4-(prop-2-yn-1-yloxy)phenyl]prop-2-en-
1-one (6a) was prepared according to the literature [26] and (E)-1,3-bis
[4-(prop-2-yn-1-yloxy)phenyl]prop-2-en-1-one (6b) was prepared accord-
ing to the literature [27]. Compounds 4-{[1-(2-oxo-1,2-dihydroquinolin-
4-yl)-1H-1,2,3-triazol-4-yl]methoxy}benzaldehydes 8a–d were previously
prepared according to literature reports [29].
. (dd, J = ., .; ., .
H)
. (d, J = .; H)
. (s; H)
.
H-m′
H-
H-a
. (s; H)
N NMR
H–N
H–N HMBC
Assignment
HSQC
.
.
., .
., .
NH
N-
3.3 General procedure for the formation of compounds
.
7a–d and 10a–d
C NMR
HSQC
HMBC
Assignment
.
., .,
.
C-a
Method A: In a 100 ml round bottom flask, to a solution of terminal
alkynes 6a,b (1.1 mmol) in 20 ml DMF, then (15 mmol%) CuSO4·5H2O
and (0.024 g,15 mmol%) sodium ascorbate were added. The reaction
mixture was stirred for 20 min at room temperature until it changes to a
yellowish green color. Then, 4-azido compounds 4a–d (1.0 mmol)
were added to the mixture. The reaction mixture was allowed to stir at
50 °C for 4 h, and another portion of sodium ascorbate (0.079 g,
0.4 mmol) and 0.024 g (15 mmol%) of CuSO4·5H2O were added. The
reaction mixture was monitored with TLC. After completion, the
mixture was poured in a beaker containing 100 g ice, diluted with H2O,
and the obtained products 7a–d and 10a–d were extracted by filtra-
tion and washed several times with ethanol.
Method B: In 100 ml round bottom flask (1 mmol) of acetophe-
none (9) and 11a–d suspended in 50 ml ethanol and 1.5 ml of 80%
NaOH with stirring until the dissolved mixture and a white solid was
formed. Then 8a–d (1 mmol) was added in one portion with stirring.
Stirring was continued for 6 h and the reaction was monitored with
TLC. After completion, the mixture was poured in a beaker containing
100 g of ice. The obtained products 7a–d and 10a–d were extracted by
filtration and washed several times with ethanol.
.
.
.
.
.
.
.
.
.
.
.
.
C-
C-p′
C-c
C-
C-
C-a
C-i
C-
C-p
C-o′
C-m
C-o
., .
.
., .
., .
., .
.
.
.
., .
.
., .,
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
C-i′
C-
C-
C-
C-b
.
.
.
.
.
.
.
., .
.
., .
.
.
.
.
., .
.
C-
C-
C-m′
C-a
C-a
3.3.1 (E)-4-(4-{[4-(3-Oxo-3-phenylprop-1-en-1-yl)phenoxy]methyl}-
1H-1,2,3-triaz-ol-1-yl)quinolin-2(1H)-one (7a): Colorless powder,
1
yield: 0.349 g (78%), m. p. 222–224 °C. – H NMR: δH = 12.28 (s, 1H,
.
H-6), 8.90 (s, 1H, H-5), 8.15 (d, J = 7.5 Hz, 2H, H-o), 7.91 (d, J = 8.5
Hz, 2H, H-o′), 7.84 (d, J = 15.6 Hz, 1H, H-b), 7.75 (d, J = 15.5 Hz, 1H, H-c),
7.65 (dd, J = 7.0, 7.0 Hz, 1H, H-12), 7.63 (t, J = 7.4 Hz, 1H, H-p), 7.57 (dd,
doublet of doublets (dd), doublet of triplets (dt), triplet of doublets J = 7.4, 7.4 Hz, 2H, H-m), 7.48 (m, 1H, H-13), 7.46 (m, 1H, H-10), 7.25
(td), and doublet of quartet (dq). Melting points were determined with (dd, J = 7.4, 7.4 Hz, 1H, H-11), 7.21 (d, J = 8.5 Hz, 2H, H-m′), 6.86 (s, 1H,
Stuart melting point instrument. Mass spectra were recorded on a H-8), 5.39 (s, 2H, H-4a). – 13C NMR: δC = 189.1 (C-a), 161.0 (C-7), 160.0
Finnigan Fab 70 eV, Al-Azhar University, Egypt. Elemental analyses (C-p′), 143.8 (C-c), 143.6 (C-9), 143.0 (C-4), 139.4 (C-13a), 137.8 (C-i),

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M.B. Alshammari et al.: Chalcones derivatized with quinolonyl-1,2,3-triazoles
Scheme 3: Synthesis of compounds 10a–d.
132.9 (C-12), 131.9 (C-p), 130.8 (C-o′), 128.7 (C-m), 128.4 (C-o), 127.8 (C-i′),
126.7 (C-5), 123.9 (C-10), 122.6 (C-11), 119.9 (C-b), 117.8 (C-8), 115.9 (C-13),
115.2 (C-m′), 114.4 (C-9a), 61.0 (C-4a). – 15N NMR: δN = 247.3 (N-1), 152.3
(N-6). – MS: m/z (%) = 448 (35) [M]+. – C27H20N4O3: Calcd. C 72.31, H
4.49, N 12.49; found C 72.44, H 4.36, N 12.40.
3.3.2 (E)-6-Methyl-4-(4-{[4-(3-oxo-3-phenylprop-1-en-1-yl)phenoxy]
methyl}-1H-1,2,3-triazol-1-yl)quinolin-2(1H)-one (7b): Colorless pow-
der, yield: 0.370 g (80%), m. p. 246–248 °C. – 1H NMR: δH = 12.22 (s, 1H,
NH), 8.89 (s, 1H, H-5), 8.15 (d, J = 7.4 Hz, 2H, H-o), 7.90 (d, J = 8.1 Hz, 2H,
H-o′), 7.84 (d, J = 15.6 Hz, 1H, H-b), 7.75 (d, J = 15.5 Hz, 1H, H-c), 7.66
(t, J = 7.0 Hz, 1H, H-p), 7.57 (dd, J = 7.3, 7.3 Hz, 2H, H-m), 7.47 (bd,
J = 7.9 Hz, 1H, H-12), 7.38 (bd, J = 7.9 Hz, 1H, H-13), 7.22 (“d”, 3H, H-m′,
10), 6.82 (s, 1H, H-8), 5.39 (s, 2H, H-4a), 2.29 (s, 3H, H-11a). – 13C NMR:
δC = 189.0 (C-a), 160.8 (C-7), 160.0 (C-p′), 143.8 (C-c), 143.4 (C-9), 142.9
Figure 4: Assigned structure of compound 10b.

M.B. Alshammari et al.: Chalcones derivatized with quinolonyl-1,2,3-triazoles
401
Table : Spectral data of compound b.
Table : Relationship between concentration of the Cu catalyst and
the reaction time for compounds a–d.
H NMR
H– H COSY
Assignment

Compounds
Conc. (mol%)
Temp. (°C)
Time (h)
Yield (%)
. (s; H)
. (s; H)
. (s; H)
. (d, J = .;
H)
. (d, J = .;
H)
. (d, J = .; .
NH-,′
H-,′
H-′,
H-o
a–d









–
–
–
.
.
H-o′
(C-4), 137.8 (C-i), 137.5 (C-13a), 133.2 (C-12), 132.9 (C-p), 131.7 (C-11),
130.8 (C-o′), 128.7 (C-m), 128.4 (C-o), 127.8 (C-i′), 126.7 (C-5), 123.1 (C-10),
119.9 (C-b), 117.8 (C-8), 115.9 (C-13), 115.2 (C-m′), 114.4 (C-9a), 61.0
(C-4a), 20.5 (C-11a). – 15N NMR: δN = 247.5 (N-1), 151.9 (N-6). – MS: m/z
(%) = 462 (17) [M]+. – C28H22N4O3: Calcd. C 72.71, H 4.79, N 12.11; found C
72.66, H 4.88, N 11.95.
H-b
H)
. (d, J = .; .
H)
. (d, J = .;
H)
. (d, J = .;
H)
. (d, J = .;
H)
H-c
., .
H-,′
H-,′
H-m
.
.
3.3.3 (E)-6-Methoxy-4-(4-{[4-(3-oxo-3-phenylprop-1-en-1-yl)
phenoxy]methyl}-1H-1,2,3-triazol-1-yl)quinolin-2(1H)-one (7c): Color-
less powder, yield: 0.405 g (85%), m. p. 230–232 °C. – 1H NMR:
δH = 12.19 (s, 1H, H-6), 8.93 (s, 1H, H-5), 8.15 (d, J = 7.4 Hz, 2H, H-o), 7.90
(d, J = 8.0 Hz, 2H, H-o′), 7.84 (d, J = 15.6 Hz, 1H, H-b), 7.75 (d, J = 15.5 Hz,
1H, H-c), 7.66 (t, J = 6.9 Hz, 1H, H-p), 7.57 (dd, J = 7.2, 7.1 Hz, 2H, H-m),
7.44 (bd, J = 8.5 Hz, 1H, H-13), 7.34 (bd, J = 7.5 Hz, 1H, H-12), 7.21
(d, J = 8.0 Hz, 2H, H-m′), 6.91 (s, 1H, H-10), 6.86 (s, 1H, H-8), 5.40 (s, 2H,
H-4a), 3.68 (s, 3H, H-11b). – 13C NMR: δC = 189.04 (C-a), 160.5 (C-7),
160.0 (C-p′), 154.5 (C-11), 143.8 (C-c), 143.0 (C-4,9), 137.8 (C-i), 134.1
(C-13a), 132.9 (C-p), 130.8 (C-o′), 128.7 (C-m), 128.4 (C-o), 127.8 (C-i′),
126.7 (C-5), 121.0 (C-12), 119.9 (C-b), 118.0 (C-8), 117.4 (C-13), 115.2 (C-m′),
114.9 (C-9a), 105.6 (C-10), 61.0 (C-4a), 55.4 (C-11b). – 15N NMR:
. (m; H)
., .,
.
H-m′,,′
. (s; H)
. (s; H)
. (s; H)
. (s; H)
H-,′
H-a′
H-a
H-a,a′
.
N NMR
.
H–N HSQC H–N HMBC
., ., .
Assignment
N-,′
N-,′
.
.
.
δ
N = 247.9 (N-1), 151.0 (N-6). – MS: m/z (%) = 479 (18) [M+1]+, 478 (40)
C NMR
HSQC
HMBC
Assignment
[M]+. – C28H22N4O4: Calcd. C 70.28, H 4.63, N 11.71; found C 70.33, H
.
., ., .,
.
C-a
4.80, N 11.88.
., .
., ., .,
.
., ., .
., .
.
., ., .,
.
., .
.
., ., .
.
., .
.
., .
., ., .,
.
C-p,,′
3.3.4 (E)-1-Methyl-4-(4-{[4-(3-oxo-3-phenylprop-1-en-1-yl)phenoxy]
methyl}-1H-1,2,3-triazol-1-yl)quinolin-2(1H)-one (7d): Colorless pow-
der, yield: 0.334 g (72%), m. p. 210–212 °C. – 1H NMR: δH = 8.89 (s, 1H,
H-5), 8.15 (d, J = 7.4 Hz, 2H, H-o), 7.91 (d, J = 8.2 Hz, 2H, H-o′), 7.84
(d, J = 15.5 Hz, 1H, H-b), 7.74 (d, J = 15.4 Hz, 1H, H-c), 7.64 (dd, J = 7.0,
7.0 Hz, 1H, H-12), 7.62 (t, J = 7.3 Hz, 1H, H-p), 7.56 (dd, J = 7.3, 7.3 Hz, 1H,
H-m), 7.46 (m, 1H, H-13), 7.46 (m, 1H, H-10), 7.25 (dd, J = 7.0, 7.0 Hz,
1H, H-11), 7.21 (d, J = 8.4 Hz, 2H, H-m′), 6.84 (s, 1H, H-8), 5.39 (s, 2H,
H-4a), 2.21 (s, 3H, H-6a). – 13C NMR: δC = 189.0 (C-a), 160.9 (C-7), 160.0
(C-p′), 143.8 (C-c), 143.5 (C-9), 142.9 (C-4), 139.4 (C-13a), 137.5 (C-i),
132.9 (C-12), 131.9 (C-p), 130.8 (C-o′), 128.3 (C-m), 128.3 (C-o), 127.8
(C-i′), 126.7 (C-5), 123.9 (C-10), 122.6 (C-11), 119.9 (C-b), 117.8 (C-8), 115.9
(C-13), 115.9 (C-m), 114.4 (C-9a), 61.0 (C-4a), 22.1 (C-6a). – C28H22N4O3:
Calcd. C 72.71, H 4.79, N 12.11; found C 72.79, H 4.65, N 12.20.
.
.
.
., .
C-p
C-,′
C-c
C-,′
.
.
.
.
.
.
.
., .
C-a,a′
C-,′
C-,′
C-i
C-o
C-o′
.
.
.
C-i′
C-,′
., .
3.3.5 (E)-4,4′-[({[(3-Oxoprop-1-ene-1,3-diyl)bis(4,1-phenylene)]
bis(oxy)}bis(methylene))-bis(1H-1,2,3-triazole-4,1-diyl)]
.
.
.
.
.
.
.
.
.
.
.
.
.
.
., .
C-,′
C-b
C-,′
C-,′
C-m′
C-m
C-a,a′
C-a′
bis(quinoline-2(1H)-one) (10a): Yellowish green powder, yield: 0.540 g
(78%), m. p. 260–262 °C. – 1H NMR: δH = 12.28 (s, 2H, 2NH), 8.91 (s, 1H,
H-5,5′), 8.90 (s, 1H, H-5′,5), 8.21 (d, J = 8.4 Hz, 2H, H-o), 7.96 (s, 1H,
DMF), 7.90 (d, J = 8.8 Hz, 2H, H-o′), 7.87 (d, J = 16.9 Hz, 1H, H-b), 7.72
(d, J = 15.4 Hz, 2H, H-c), 7.65 (dd, J = 7.5, 7.5 Hz, 2H, H-12,12′), 7.48 (d,
J = 8.2 Hz, 2H, H-10,10′), 7.46 (d, J = 8.1 Hz, 2H, H-13,13′), 7.25 (m, 4H,
H-m,m′,11,11′), 6.87 (s, 2H, H-8,8′), 5.44 (s, 2H, H-4a′), 5.39 (s, 2H,
H-4a), 2.90 (s, 3H, DMF), 2.74 (s, 3H, DMF). – 13C NMR: δC = 187.3 (C-a),
162.3 (DMF), 161.8, 161.0 (C-p,7,7′), 159.9 (C-p′), 143.6 (C-9,9′), 143.0
.
., .
.
.
.
.
.
C-a
C-a,a′
., ., .

402
M.B. Alshammari et al.: Chalcones derivatized with quinolonyl-1,2,3-triazoles
(C-c), 142.8 (C-4,4′), 139.4 (C-13a,13a′), 131.9 (C-12,12′), 131.1 (C-i), 130.8 1′), 146.9 (N-6, 6′). – MS: m/z (%) = 716 (24). – C41H32N8O5: Calcd. C 68.71,
(C-o), 130.7 (C-o′), 128.0 (C-i′), 126.8, 126.7 (C-5,5′), 123.9 (C-10,10′), H 4.50, N 15.63; found C 68.88, H 4.41, N 15.77.
122.6 (C-11,11′), 119.8 (C-b), 117.7 (C-8,8′), 116.0 (C-13,13′), 115.2 (C-m′),
114.8 (C-m), 114.4 (C-9a,9a′), 61.1 (C-4a′), 61.0 (C-4a),. – 15N NMR:
δN = 247.5 (N-1,1′). – MS: m/z (%) = 688 (16). – C39H28N8O5: Calcd. C
Acknowledgments: The authors thank the Deanship of
Scientific Research at Prince Sattam Bin Abdulaziz Uni-
versity under the research project No. 10302/1/2019.
Author contributions: All the authors have accepted
responsibility for the entire content of this submitted
manuscript and approved submission.
Research funding: The work of this paper was not
supported by funds.
Conflict of interest statement: The authors declare no
conflict of interest.
68.02, H 4.10, N 16.27; found C 68.12, H 3.97, N 16.35.
3.3.6 (E)-4,4′-[({[(3-Oxoprop-1-ene-1,3-diyl)bis(4,1-phenylene)]-
bis(oxy)}bis(methylene))-bis(1H-1,2,3-triazole-4,1-diyl)]
bis(6-methylquinoline-2(1H)-one) (10b): Yellowish green powder,
yield: 0.608 g (79%), m. p. 285–287 °C. – 1H NMR: δH = 12.22 (s, 2H, H-6,
6′), 8.90, 8.89 (2 × s, each 1H, H-5,5′), 8.21 (d, J = 8.5 Hz, 2H, H-o), 7.91
(d, J = 8.6 Hz, 2H, H-o′), 7.87 (d, J = 15.4 Hz, 1H, H-b), 7.72 (d, J = 15.4 Hz,
1H, H-c), 7.49 (d, J = 8.3 Hz, 2H, H-12, 12′), 7.39 (d, J = 8.4 Hz, 2H, H-13,
13′), 7.28 (d, J = 8.4 Hz, 2H, H-m), 7.21 (m, 4H, H-m′, 10, 10′), 6.82 (s, 2H,
H-8, 8′), 5.45(s, 2H, H-4a′), 5.39 (s, 2H, H-4a), 2.30 (s, 6H, H-11a, 11a′)
–
13C NMR: δC = 187.3 (C-a), 161.7, 160.8 (C-p, 2, 2′), 159.9 (C-p′), 143.4
(C-9, 9′), 143.0 (C-c), 142.9, 142.8 (C-4, 4′), 137.5 (C-13a, 13a′), 133.2 (C-12,
12′), 131.8 (C-11, 11′), 131.1 (C-i), 130.8 (C-o), 130.7 (C-o′), 127.9 (C-i′),
126.8, 126.7 (C-5, 5′), 123.1 (C-10, 10′), 119.8 (C-b), 117.8 (C-8, 8′), 115.9
(C-13, 13′), 115.2 (C-m′), 114.8 (C-m), 114.4 (C-9a, 9a′), 61.1 (C-4a′), 61.0
(C-4a), 20.5 (C-11a, 11a′). – 15N NMR: δN = 247.6 (N-1, 1′), 152.0 (N-6, 6′),
N-2, 2′, 3, 3′ n/o. – MS: m/z (%) = 717 (16) [M+1]+, 716 (35) [M]+.
– C41H32N8O5: Calcd. C 68.71, H 4.50, N 15.63; found C 68.66, H 4.61, N
15.49.
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3.3.7 (E)-4,4′-[({[(3-Oxoprop-1-ene-1,3-diyl)bis(4,1-phenylene)]
bis(oxy)}bis(methyl-ene))bis(1H-1,2,3-triazole-4,1-diyl)]
bis(6-methoxyquinoline-2(1H)-one) (10c): Yellowish green powder,
1
yield: 0.606 g (81%), m. p. 226–228 °C. – H NMR: δH = 12.19 (s, 2H,
2NH), 8.94 (s, 1H, H-5/5′), 8.93 (s, 1H, H-5′/5), 8.19 (d, J = 9.1 Hz, 2H, H-o),
7.89 (d, J = 8.6 Hz, 2H, H-o′), 7.83 (m, 1H, H-b), 7.72 (m, 1H, H-c), 7.44
(d, J = 9.0 Hz, 2H, H-13, 13′), 7.34 (dd, J = 8.9, 2.2 Hz, 1H, H-12, 12′), 7.27
(d, J = 8.5 Hz, 2H, H-m), 7.20 (d, J = 8.4 Hz, 2H, H-m′), 6.91 (d, J = 1.4 Hz,
2H, H-10, 10′), 6.86 (s, 2H, H-8, 8′), 5.45 (s, 2H, H-4a), 5.40 (s, 2H, H-4a′),
3.68 (s, 6H, H-11b, 11b′). – 13C NMR: δC = 187.3 (C-a), 161.7 (C-7, 7′), 160.5
(C-p), 159.8 (C-p′), 154.5 (C-11), 143.1, 142.9 (C-c, 4, 4′, 9, 9′), 134.1
(C-13a, 13a′), 130.8 (C-o), 130.6 (C-o′), 127.9 (C-i′), 126.65, 126.58 (C-5,
5′), 121.0 (C-12, 12′), 119.9 (C-b), 118.0 (C-8, 8′), 117.4 (C-13, 13′), 114.9
(C-m, m′, 9a, 9a′), 105.6 (C-10, 10′), 61.1 (C-4a), 61.0 (C-4a′), 55.4 (C-11b,
11b′). – 15N NMR: δN = 247.8 (N-1, 1′), 151.1 (N-6, 6′). – m/z (%) = 748
(14). – C41H32N8O7: Calcd. C 65.77, H 4.31, N 14.97; found C 65.66, H
4.29, N 15.11.
10. Andries K., Verhasselt P., Guillemont J., Göhlmann H. W. H.,
Neefs J.-M., WinklerH., Van GestelJ., Timmerman P., ZhuM., LeeE.,
Williams P., de Chaffoy D., Huitric E., Hoffner S., Cambau E.,
Truffot-Pernot C., Lounis N., Jarlier V. Science (Washington, D.C.)
2005, 307, 223–227.
3.3.8 (E)-4,4′-[({[(3-Oxoprop-1-ene-1,3-diyl)bis(4,1-phenylene)]
bis(oxy)}bis(methylene)-)bis-(1H-1,2,3-triazole-4,1-diyl)]bis-(N-
methylquinoline-2(1H)-one) (10d): Yellowish green powder, yield:
0.520 g (73%), m. p. 205–207 °C. –1HNMR:δH =8.91(s,1H, H-5/5′), 8.90 (s,
1H, H-5′/5), 8.21 (d, J = 8.6, 2H, H-o), 7.91 (d, J = 8.8, 2H, H-o′), 7.83
(d, J = 16.5 Hz, 1H, H-b), 7.79 (dd, J = 8.2, 7.0 Hz, 2H, H-12, 12′), 7.74
(d, J = 8.2 Hz, 2H, H-13, 13′), 7.73 (d, J = 17.8 Hz, 1H, H-c), 7.46 (d, J = 8.0
Hz, 2H, H-10, 10′), 7.35 (dd, J = 7.5, 7.5 Hz, 2H, H-11, 11′), 7.28 (d, J = 8.6 Hz,
2H, H-m), 7.21 (d, J = 8.4 Hz, 2H, H-m′), 7.00 (s, 2H, H-8, 8′), 5.45 (s, 2H,
H-4a), 5.39 (s, 2H, H-4a′), 3.73 (s, 6H, H-6a, 6a′). – 13C NMR: δC = 187.3
(C-a), 161.8 (C-7, 7′), 160.3 (C-p), 159.9 (C-p′), 143.0 (C-c), 142.8, 142.6 (C-4,
4′, 9, 9′), 140.1 (C-13a, 13a′), 132.3 (C-12, 12′), 131.1 (C-i), 130.8 (C-o), 130.7
(C-o′), 128.0 (C-i′), 127.0, 126.9 (C-5, 5′), 124.4 (C-10, 10′), 122.7 (C-11, 11′),
119.8 (C-b), 117.3 (C-8, 8′), 115.6, 115.5 (C-9a, 9a′, 13, 13′), 115.2 (C-m′), 114.8
(C-m), 61.1 (C-4a), 61.0 (C-4a′), 29.6 (C-6a, 6a′). – 15N NMR: δN = 246.7 (N-1,
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