1.

1 Introduction
Chalcones 1,3-diphenyl-2-propen-1-ones , are based on two aryl moieties bridged via
an alpha,beta- unsaturated carbonyl group. These molecules have a -C=O-CH=CH-
ketoethylenic moiety in their structure, in their aromatic rings, they have a delocalized
pi-electron- containing order
O

(2E)-1,3-diphenylprop-2-en-1-one

(2017) Chalcone bearing pyrrole : Series of pyrrole-based chalcone derivatives were

reported through the classical Claisen–Schimdt condensation reaction protocol [1]. The
synthesized compounds displayed potential activity on the inhibition of CYP1 isoform,
the reaction afford products of various derivatives 18 starting from aromatic aldehyde
derivatives A and pyrrole-based acetophenone B in basic media. The 2-pyrrole chalcone
derivatives C were possible to synthesize using either a liquid phase or solid through a
grinding method with moderate to good yields.

Chalcone bearing Imidazole : imidazole-based chalcone-substituted derivatives using

the Claisen–Schmidt condensation reaction between ethenone D and various para-
substituted aromatic aldehyde derivative D, A mixture of ethanone D and para-E
benzaldehyde 26 [2] in ethanol and aqueous potassium hydroxide was E and stirred at
room temperature. The resulting product was kept overnight in a refrigerator, and the
solid was filtered off, washed with water, and recrystallized from ethanol and methanol
to afford pure imidazole chalcone derivatives F
O
O
O
H
CH3
CH3 KOH, EtOH N N
R CH3
N N + R

25 E
26
D
F R=H, OH, OCH3, CH3,N2O2, CI,
27,
N(CH3)2,C2H5, Br, F , CF3
Chalcone bearing Pyridine : imidazo-pyridine derivatives through the condensation of
aryl methyl ketone and aryl aldehyde in the presence of alcoholic alkali media [3] The
synthesis mixture of pyridine-3-carbaldehyde G and ethenone H was refluxed in
methanol, followed by the addition of NaOH as a catalyst. The crude was poured on to
crushed ice, and the resulting product was further recrystallized from dichloromethane
to give compound I.
Cl O CH3 CH3
anhydrous Cl
Cl
AIC3 N
+ Cl
N NH2
Cl
O 50 N

48 H2 51
47 Cl 49
POCI3
CH3
CH3 DMF
MeOH, 10% KOH N
N Cl
O N
N Cl
O H
R CH3
54
H
R
I 53
O

52
H G

Chalcone Bearing piperazine : synthesis of piperazine-chalcone hybrid derivatives as

potential vascular endothelial growth factor receptor-2 inhibitors [4] A mixture of a
derivative of acetophenone J and corresponding aldehyde derivatives K was dissolved
in 10% alcoholic sodium hydroxide and stirred at room temperature. After the reaction
completed, the precipitate was filtered, washed, dried, and recrystallized from ethanol
to afford the target compounds L.
O
CH2

CH3
NH CH3
+F DMSO, heating
HN O
N +
69 70 at 110 oC, 24 h
H CH3
N
J
71
72
H K
AIcohoIic NaOH
(10%)

stirring 5 h

N
L
73

R= 2-CN, 3-CN, 2-F , 3-F , 2-F , 2-OH-5-NO 2,2- OCH3,

Chalcone Bearing Benzimidazole : A series of benzimidazole-based chalcone
derivatives were synthesized and reported using the Claisen–Schmidt reaction as
potential Topo II-targeting anticancer agents [5] . Benzimidazole derivative N was
obtained through refluxing o-phenylenediamine M with glycolic acid in the presence
of HCl. The substituted benzimidazole-2-methanol O was synthesized through the
alkylation of compound N using a benzyl bromide in the presence of K2CO3.
Subsequently, substituted benzimidazole-2-carbaldehyde derivatives P were obtained
from O through oxidation using a Dess–Martin protocol. Compounds O were finally
prepared from P through a Claisen–Schmidt reaction in the presence of appropriate
acetophenone derivatives.

NH2 H
GIycoIic acid, 4N HCI, N OH
N
102, benzyI bromides,
NH2 N K2 CO3
100 oC, 6 h N OH
100 101
M N DMF , rt, 24 h
103
O
Dess-Marttin periodinane,
CH3 DCm, 0 oC, 1h

CH2

105, ArCOCh3,
CH3
105 EtOH, N

10% NaOH, rt, 1 h

N O

104
P

Chalcone Bearing Quinoline : A series of quinoline-based chalcone derivatives were

synthesized and reported by Thirumurugan and co-workers through the common aldol
condensation reaction[6] Quinoline-based chalcones N-quinoline-2-carboxamides were
synthesized using quinoline-2-carboxylic acid Q subjected to ethenone R in TEA using
TBTU as the base with reflux for 3 h at room temperature .
 NH2

TBTU, TEA
O
H
+ CH3
DMF , RT , 3h NH
N N CH3
O O
O

134
133 135
NaOH/EtOH
R - CHO RT , 30min
136
Q
R= a = 4-CI(C6H4),
b = C6H5, OH
c = 2-OcH3(C6H4), NH
d = 3,4,5-(OCH3)3(C6H2), N CH3
R
e = 4-OH(C6H5), O
f = 3-Br(C6H5),
g = 4-OCH3(C6H5) R137 (a-g)

References
[1]. Özdemir, A.; Altıntop, M. D.; Sever, B.; Gençer, H. C.; Kapkaç,H. A.; Atlı, Ö.;
Baysal, M. A new series of pyrrole-based chalcones:synthesis and evaluation of
antimicrobial activity, cytotoxicity, and genotoxicity. Molecules. 2017, 22 (12), 2112.
[2] .Liu, Y. T.; Sun, X. M.; Yin, D. W.; Yuan, F. Syntheses and biological activity of
chalcones-imidazole derivatives. Res. Chem.Intermed. 2013, 39 (3), 1037−1048.
[3] .Farghaly, T. A.; Masaret, G. S.; Muhammad, Z. A.; Harras, M. F. Discovery of
thiazole-based-chalcones and 4-hetarylthiazoles as potent anticancer agents: Synthesis,
docking study and anticancer activity. Bioorganic chemistry 2020, 98, 103761
[4] . Ahmed, M. F.; Santali, E. Y.; El-Haggar, R. Novel piperazine− chalcone hybrids
and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis,
molecular docking studies, and anticancer evaluation. Journal of enzyme inhibition and
medicinal chemistry 2021, 36 (1), 308−319.
[5] . Zhou, W.; Zhang, W.; Peng, Y.; Jiang, Z. H.; Zhang, L.; Du, Z. Design, synthesis
and anti-tumor activity of novel benzimidazole- chalcone hybrids as non-intercalative
topoisomerase II catalytic inhibitors. Molecules. 2020, 25 (14), 3180.
[6].Thirumurugan, C.; Vadivel, P.; Lalitha, A.; Lakshmanan, S.Synthesis,
characterization of novel quinoline-2-carboxamide based chalcone derivatives and their
molecular docking, photochemical studies. Synth. Commun. 2020, 50 (6), 831−839.