Efficient ultrasound-assisted synthesis, spectroscopic, crystallographic and biological investigations of pyrazole-appended quinolinyl chalcones

Article abstract of DOI:10.1016/j.molstruc.2014.10.026

Two series of new quinolinyl chalcones containing a pyrazole group, 3a-f and 4a-r, have been synthesized by Claisen-Schmidt condensation of the derivatives of 2-methyl-3-acetylquinoline with either substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde or 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde in 76-93% yield under ultrasonic method. The compounds were characterized using IR, ¹H NMR and ESI-MS spectroscopic methods and, for representative compounds, by X-ray crystallography. An E-configuration about the CC ethylene bond has been established via ¹H NMR spectroscopy and X-ray crystallography. These compounds show promising anti-microbial properties, with 4a and 3e being the most potent against bacterial and fungal strains, respectively and the methoxy substituted compounds showed moderate anti-oxidant activity.

Full text of DOI:10.1016/j.molstruc.2014.10.026

Accepted Manuscript
Efficient ultrasound-assisted synthesis, spectroscopic, crystallographic and bi-
ological investigations of pyrazole-appended quinolinyl chalcones
R. Prasath, P. Bhavana, S. Sarveswari, Seik Weng Ng, Edward R.T. Tiekink
PII:
S0022-2860(14)01039-4
DOI:
http://dx.doi.org/10.1016/j.molstruc.2014.10.026
MOLSTR 21022
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Revised Date:
Accepted Date:
28 September 2014
13 October 2014
13 October 2014
Please cite this article as: R. Prasath, P. Bhavana, S. Sarveswari, S.W. Ng, E.R.T. Tiekink, Efficient ultrasound-
assisted synthesis, spectroscopic, crystallographic and biological investigations of pyrazole-appended quinolinyl
chalcones, Journal of Molecular Structure (2014), doi: http://dx.doi.org/10.1016/j.molstruc.2014.10.026
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Efficient ultrasound-assisted synthesis, spectroscopic, crystallographic and
biological investigations of pyrazole-appended quinolinyl chalcones
a
a
b
c
c
R. Prasath *, P. Bhavana , S. Sarveswari , Seik Weng Ng , Edward R. T. Tiekink
a
Department of Chemistry, Birla Institute of Technology and Science (BITS), Pilani - K. K.
bBirla Goa Campus, Zuarinagar, Goa - 403 726, India
cCenter for Organic and Medicinal chemistry, VIT University, Vellore-632014, India
Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
Corresponding Author
Complete Postal Address
: R. Prasath
: R. Prasath,
Senior Research Fellow,
Department of Chemistry,
Birla Institute of Technology and Science (BITS), Pilani
–
K. K. Birla Goa Campus,
Zuarinagar, Goa – 403 726, India.
: drrprasath24487@gmail.com
: + 91 832 2580335 (Office)
E-mail address
Telephone
+91 9503792955 (Mobile)
Fax Number
: + 91 832 2557033
Abstract
Two series of new quinolinyl chalcones containing a pyrazole group, 3a-f and 4a-r, have
been synthesized by Claisen-Schmidt condensation of the derivatives of 2-methyl-3-
acetylquinoline with either substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde or 5-chloro-
3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde in 76-93% yield under ultrasonic method.
1
The compounds were characterized using IR, H NMR and ESI-MS spectroscopic methods
and, for representative compounds, by X-ray crystallography. An E-configuration about the
1
C=C ethylene bond has been established via H NMR spectroscopy and X-ray
crystallography. These compounds show promising anti-microbial properties, with 4a and 3e
being the most potent against bacterial and fungal strains, respectively and the methoxy
substituted compounds showed moderate anti-oxidant activity.
Keywords:
Chalcones; Quinoline; Pyrazole; Claisen-Schmidt condensation; Anti-microbial activity.
ꢀ
ꢁ
ꢁ

1. Introduction
Chalcones and their derivatives are known for their wide range of applications in the field of
pharmaceutics and also in the manufacture of pesticides, cosmetics, etc. [1,2]. For example,
they have been found to act as anti-inflammatory, analgesic, anti-platelet, anti-ulcerative,
anti-malarial, anti-cancer, anti-viral, anti-leishmanial, antioxidant, anti-tubercular, anti-
hyperglycemic and anti-tumour agents [3, 4]. In terms of putative biological mechanisms of
action, reports indicate chalcone derivatives inhibit the release of chemical mediators [5],
tyrosinase [6], leukotriene B4 [7] and aldose reductase [8]. In addition, chalcones separated
by bichromophoric moieties, such as a vinyl chain and a carbonyl group, were found to be
effective photosensitive materials and to exhibit potential nonlinear optical (NLO) properties
[9, 10]. Metal chelates of chalcones are found to be effective catalysts and potential anti-
cancer agents [11, 12].
Nitrogen heterocycles are of special interest because they constitute an important class of
natural and non-natural products, many of which exhibit useful biological activities, such as
anti-bacterial, anti-fungal, anti-viral and anti-inflammatory, and also demonstrate distinctive
optical properties [13]. Quinolines, which form a part of the structure of many alkaloids, are
an important class of nitrogen heterocyclic compounds that display versatile biological
activity [14]. They are found to form the basis of many drugs used in the treatment of cancer
and inflammatory diseases [15]. Their high lipophilicity and conformational rigidity together
with metabolic stability and oral bioavailability [16], lead to the study of these heterocycles
for therapeutic purposes. Studies reveal that incorporation of a pyrazole moiety into various
heterocyclic ring systems results in useful molecules from the biological point of view [17,
18]. Thus, many pyrazole derivatives are reported to have a broad spectrum of biological
activities, such as anti-inflammatory, anti-fungal, herbicidal, anti-viral and are A3 adenosine
receptor antagonists [13, 17, 18]. Several drugs, including Celecoxib® [19] and
Rimonabant® [20], utilize pyrazole in their molecular core [21].
Compared to conventional methods, ultrasound irradiation is considered as a clean and useful
technique in organic synthesis as the procedure can be more convenient and is cost effective
[
22, 23]. A large number of organic reactions can be carried out in higher yield, short
reaction time and/or milder conditions under ultrasonic irradiation. In this way, ultrasound
has proved extremely useful in the synthesis of a wide range of organic, inorganic and
ꢂꢁ
ꢁ

nanostructured materials [24, 25]. The introduction of high-power ultrasound waves (i.e.
sound energy with frequencies in the range 15 kHz-1 MHz) into liquid reaction mixtures is
known to cause a variety of chemical transformations.
Herein, the synthesis by conventional (CON) and ultrasonic (US) synthetic methods of two
new series of pyrazole-appended quinolinyl chalcones, 3a-f and 4a-r, featuring pyrazole and
quinoline linked via a chalcone unit (Fig. 1), are reported. Spectroscopic properties and
biological activities of the synthesized compounds are described as well as the crystal
structures of representative compounds (3c and 4h; the latter as a hydrate). The synthetic
pathway of target molecules is shown in Scheme 1.
2
. Chemistry
The precursors of the title pyrazole-appended quinoline chalcones were derivatives of 2-
methyl-3-acetylquinoline and of pyrazole-4-carboxaldehyde. Derivatives of pyrazole-4-
carboxaldehyde, 1a-d, were obtained in good yield by a modified Vilsmeier-Haack
formylation of the corresponding acetophenone phenylhydrazone and 5-chloro-3-methyl-1-
phenyl-1H-pyrazole [26-29] and the derivatives of 2-methyl-3-acetylquinoline, 2a-f, were
synthesized by Friedlander cyclization of substituted 2-aminobenzophenone, 2-
aminobenzaldehyde or 2-aminoacetophenone with acetylacetone in acidic medium [30-33].
The synthesis of pyrazolyl-quinoline chalcone derivatives, 3a-f and 4a-r, were carried out by
a Claisen-Schmidtꢀ condensation of substituted 2-methyl-3-acetylquinolines (where R
CH , C or 2-ClC , R = H, Br, Cl or NO and R = H or Br) with the corresponding
3 6 4
substituted pyrazole-4-carboxaldehyde (where R , 4-BrC or 4-OCH C H )
2
= H,
3
6
H
5
6
H
4
3
2
4
1
= CH3,
6
C H
5
6
H
4
using KOH as catalyst in ethanol at room temperature (Table 1). In the condensation
reactions of 1a with 2a-f, on using ethanol as the solvent, pyrazolyl-quinoline chalcone
derivatives 3a-f were obtained where the original pyrazolyl-bound chloro atom was
substituted by an ethoxy group.
The reaction time for the conventionally synthesized chalcones is 12 hours, while reaction
time for the synthesis by ultrasonic method is 15 minutes. The purity and yield of the product
by ultrasound method was found to be better than conventionally synthesized ones. It is
observed that the variation of reaction temperature had a considerable influence on the yield
of the product. All reactions were normally carried out at 30-35 ºC. On increasing the
reaction temperature to 45 ºC, a drastic reduction in the yield was noted.
ꢃꢁ
ꢁ

The effect of the catalyst on the yield of chalcones 3a and 4a was also studied. As shown in
Table 2, the catalytic effect of K CO , KOH, NaOH and EtONa are listed. It was found that
2
3
KOH was the most effective of those evaluated. For example, under the same reaction
conditions, when KOH was used as the catalyst, the yields were 76% and 90% for 3a and 4a,
respectively, whereas when K CO , NaOH or EtONa were used as the catalyst, the yields
2
3
were less than 61% and 66% for 3a and 4a, respectively. The study also showed that the
molar ratio of potassium hydroxide to starting materials also had a significant effect on the
yield of compounds 3a-f and 4a-r, with the optimum molar ratio of starting materials to
potassium hydroxide being 1:0.75.
3. Results and discussion
3
.1. Spectral characterisation
The absorption data of compounds 3a-f and 4a-r were recorded in dichloromethane solution
-
5
(
concentration 10 M) and the results are collated in Table 3. Two or more absorption bands
were observed in the linear absorption spectra of all molecules in the wavelength range 229
to 347 nm. The spectra bear a close resemblance owing to the similarity in structure. As
noted from Table 3 (and Supplementary material Fig. S1), the maximum absorption band for
compounds 3a-f, having an electron-donating methyl group in the 3-position of the pyrazole
ring, is blue shifted compared with compounds 4a-r which have an aromatic ring in the
corresponding 3-position. By contrast, it is observed that the substituent in 6-position of
quinoline moiety exerts almost no influence on the absorption maximum.
The IR spectra of the compounds 3a-f and 4a-r exhibited absorption bands between 1644-
-1
-1
1
682 cm and 1560-1625 cm corresponding to the νc=o and νc=c functionalities. The
stretching frequency of the carbonyl group in the chalcone molecule is not greatly affected by
the position of the respective substituents on the pyrazole and quinoline moieties. The mass
+
spectra (ESI-MS) of the compounds 3a-f and 4a-r showed [M+H] peaks (Table 3).
The synthesis of chalcones 3a-f and 4a-r via the Claisen-Schmidt condensation leads to the
1
exclusive formation of an E-configuration about the C=C bond as established by H NMR
spectroscopy [34] and X-ray crystallography (see below). The predominance of the E-
configuration is a result of the more favourable anti-periplanar elimination of the hydroxide
1
group from the carbanion intermediate (see Supplementary material Fig. S2). In the H NMR
ꢄꢁ
ꢁ

spectra, the magnitude of the coupling constant (JHαHβ = 16.0-16.5 Hz) for the vinylic protons
Fig. 2) has been used to verify the E-configuration, as summarised in Table 3. It is noted
that the chemical shift of H is deshielded compared to that of H . This is explained by the
existence of formal positive charge on C (Fig. 2), arising as a result of resonance distribution
of π-electron density in going from one canonical form (a) to the other (b), which causes the
shift of H signal to lower field. Compounds 3a-f each showed a prominent quartet between
(
β
α
β
β
δ 4.40-4.55 ppm and a triplet between δ 1.35–1.41 ppm with an integrated intensity ratio 2:3,
1
indicating the presence of an ethoxy group, see Fig. 3 for the H NMR spectrum of 3c.
Although there is no discernible trend in the magnitude of δHα or δHβ as a function of the
nature of the substituent on pyrazolyl ring, there is detectable trend due to the substituents at
the 4-position of the quinoline ring. It can be discerned from Fig. 4(a), for 4g, and Table 2,
the chemical shift due to Hα in compounds 3a, 3b, 4a, 4b, 4g, 4h, 4m and 4n is deshielded
compared to those in the remaining compounds. When the 4-position of quinoline was
unsubstituted or occupied by a methyl group, the resonance of Hα is deshielded, this is due to
the s-trans conformation (see Supplementary material Fig. S3). The s-trans conformation of
the methyl substituted quinoline chalcone, 4h, was also confirmed by X-ray crystallography
(
see below). It has been reported that an increase in the steric bulk of the substituent attached
to the carbonyl carbon favours the s-cis conformation [35]. It is noted that each of the H and
protons in 3e, 4e, 4k and 4q is deshielded compared to those of the other chalcones in the
5
H
7
respective series. This is explained by the existence of an electron-withdrawing bromine or
nitro group at the 6-position of the quinoline ring. As expected, the effect due to the nitro
group is greater than that exerted by the bromine substituent (see Fig. 4(b) for spectrum of
4k).
3
.2. X-ray crystallography
Crystals for representative molecules 3c and 4h (characterised as a monohydrate) were
obtained by slow evaporation of acetone solution of the respective compound.
Crystallographic data and final refinement details are given in Table 4. The molecular
structure of 3c is shown in Fig. 5 from which it can be seen the configuration about the
C18=C19 double bond is E, confirming the spectroscopic analysis. The pyrazolyl ring is
planar with the r.m.s. deviation of the fitted atoms being 0.005 Å, and the sum of the angles
2
about the N1 atom of 360° confirms its sp character. The N1-attached phenyl ring is
inclined to the five-membered ring forming a dihedral angle of 24.77(15)°, as is the ethylene
ꢅꢁ
ꢁ

group, with the C18–C19–C22–C21 torsion angle being -167.0(2)°. A significant twist in the
molecule occurs about the C17–C18 bond (the C1–C9–C17–C18 torsion angle = 70.4(3)°) so
that the plane through the quinolinyl atoms (r.m.s. deviation = 0.025 Å) forms a dihedral
angle of 84.03(13)° with the pyrazolyl ring, indicating an approximate orthogonal
relationship. The C10-phenyl ring is almost orthogonal to the quinolinyl ring to which it is
attached (dihedral angle = 70.60(12)°). This orientation places the ring directly over a C24-
bound H atom but the H...ring centroid separation of 3.21 Å is not indicative of a significant
interaction between these components of the structure.
2
The molecular structure of 4h in 4h.H O is shown in Fig. 6 and presents analogous features
as described for 3c, starting with an E-configuration about the C16=C17 double bond. The
pyrazolyl ring (r.m.s. deviation = 0.003 Å; sum of angles around N1 = 360º) forms dihedral
angles of 13.9(2) and 33.5(2)° with the N- and C-bound phenyl rings, respectively. Twists
are evident in the central part of the molecule as evidenced by the C7–C8–C16–C17 and
C17–C18–C21–C20 torsion angles of 16.1(7) and 102.2(5)°, respectively. The dihedral angle
of 72.68(18)° between the pyrazolyl and quinolinyl (r.m.s. deviation = 0.008 Å) indicates a
near orthogonal relationship.
The diagram in Fig. 7 shows the overlay of the molecules of 3c and 4h, and highlights the
similarity in conformation. The major difference between the molecules relates to the
relative orientation of the quinolinyl ring with respect to the pyrazolyl ring. Thus, in 3c, all
atoms comprising the quinolinyl ring lie to one side of the pyrazolyl ring, whereas in 4h, the
atoms comprising the fused ring system lie to either side of the pyrazolyl plane.
The crystal packing in 3c is dominated by C H...N, C H...π and π. ..π interactions; the
carbonyl-O1 atom is involved in an intramolecular C H...O contact and does not participate
in significant stabilisation of the crystal structure. The quinolinyl-N3 atom forms an
interaction with a pyrazolyl-bound methyl-H atom, and the methyl-H from the ethyl group
6
forms a donor interaction with the C ring of the quinolinyl residue. These combine to form
supramolecular chains along the a-axis. These are connected into layers along the b-axis by
π. ..πinteractions between centrosymmetrically related pyrazolyl-bound phenyl rings. A view
of the unit cell contents is shown in Supplementary material Fig. S4 and geometric
ꢆꢁ
ꢁ

parameters characterising the intermolecular interactions are summarised in the figure
caption.
2
The crystal packing in 4h.H O is dominated by conventional water-O H...O(carbonyl) and
water-O H...N(quinolinyl) hydrogen bonding whereby the solvent water molecule bridges
molecules into a supramolecular chain along the a-axis (Supplementary material Fig. S5(a)).
The water-O1w atom also participates in two C H...O interactions and the carbonyl-O1 one,
to construct a three-dimensional architecture. Additional stability to the crystal structure is
afforded by π. ..πinteractions occurring between centrosymmetrically related C1-C6 rings and
between centrosymmetrically related C24-C29 rings of the quinolinyl residue
(
Supplementary material Fig. S5(b)).
3
.3. In vitro antioxidant activity (DPPH method)
The compounds 3a-f and 4a-r were evaluated for their in vitro free radical scavenging
activity by the 2,20 diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method [36].
Stock solutions of different compounds (1 mM) were mixed with DPPH methanol solution
(
0.5 mL, 0.3 mM) in 3 mL of total reaction mixture and allowed to react at room temperature.
After 30 min, absorbance values were measured at 520 nm and converted to % antioxidant
activity. For a comparative study the butylated hydroxyl anisole (BHA) was used as the
standard. The percentage inhibition activity was calculated by following formula:
%
antioxidant activity= [1- OD of test compound/OD of control compound] × 100.
Whereas compounds 3a-f and 4a-l showed inhibition < 15%, compounds 4m-r, i.e. carrying
methoxy substituents, exhibited moderate activity; data for 4m-r are summarized in Table 5.
3
.4. Anti-microbial assay
It is known that the configuration at the C=C bond of a chalcone can play a significant role in
its biological activity. For example, Larsen et al. have prepared a series of chalcone
analogues, locked in either the Z- or the E-configuration, and evaluated their anti-plasmodial
activity [37]. It was shown that the Z-locked analogues were nearly inactive, whereas the E-
locked analogues were equipotent to the parent chalcones, indicating that the E-form is the
active isomer. The synthesized compounds were screened in vitro for anti-bacterial and anti-
fungal activity against various gram-positive and gram-negative bacteria, and fungal strains
ꢇꢁ
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using agar cup-plate method [38, 39]. The microbial strains studied were Escherichia coli (E.
coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), Candida
albicans (C.albicans) and Aspergillus niger (A. niger). Chloramphenicol® and Grisofulvin®
were used as the reference standard drug for the anti-bacterial and anti-fungal study,
respectively, at concentrations of 30μg/ml. The zone of inhibition for 3a-f and 4a-r was
measured for various strains, and the results are summarised in Table 6. Compounds 3a, 3e,
4a, 4f, 4k and 4q exhibited high activity on both gram-positive and gram-negative bacteria.
Among the studied compounds, 4a showed maximum activity (21.44 mm) towards
Escherichia coli. From the screening data, it is clear that electron-withdrawing bromine
group increases the anti-microbial activities of the compounds.
4
. Experimental
4.1. Materials and methods
The substituted pyrazole-4-carbaldehyde [26-29] and 2-methyl-3-acetylquinoline [30-33]
were synthesized according to literature methods. The reactions were monitored by thin layer
chromatography (TLC) using a precoated silica gel 60F254 thin layer plates (Merck). Column
chromatography was carried out using silica gel (230–400 mesh, Merck) as the packing
material. The detailed syntheses of the precursors were given in the supplementary material.
The reactions were carried out using Microson Ultrasonic Cell Disrupter; Misonix, Inc.,
USA. Melting points (mp) were determined using Bio Techniques India melting point
apparatus and are uncorrected. Optical absorption spectra were recorded on a JASCO V-570
model UV/VIS/NIR spectrophotometer using quartz cells of 10 mm path length. IR spectra
-
were recorded in KBr pellets on a Perkin Elmer RX1 spectrophotometer in the 4,000–450 cm
1
1
region. The H NMR spectra were recorded on Bruker AVANCE-400 and Bruker
AVANCE III-500 MHz spectrometers in deuterated chloroform with tetramethylsilane as the
internal standard. Elemental analysis was performed on Elementar Vario EL III elemental
analyser. ESI-Mass spectra were recorded on Micromass Quarto II mass spectrometer.
For the X-ray crystallographic studies, intensity data were measured at 100 K on an Agilent
Technologies SuperNova Dual CCD with an Atlas detector fitted with Mo Kαradiation with
θmax = 25.0° for 3c, and fitted with Cu Kαradiation with θmax = 74.4° for 4h; 4h was
characterised as a monohydrate. Data processing and absorption correction were
accomplished with CrysAlis PRO [40]. The structures were solved by direct methods with
ꢈꢁ
ꢁ

SHELXS-97 [41] and refinement (anisotropic displacement parameters, hydrogen atoms in
2
2
2
the riding model approximation and a weighting scheme of the form w = 1/[σ(F
o
) + (aP) +
2
2
2
o c
bP] for P = (F + 2F )/3) was on F by means of SHELXL-97 [41]. In 4h, a relatively high
anisotropic displacement ellipsoid was noted for the water molecule of crystallization but,
multiple sites were not resolved. The water molecule was modelled with the ISOR command
in SHELXL97 [41]; it is noted that both hydrogen atoms form chemically sensible hydrogen
bonding interactions. Molecular structure and atomic labelling scheme were drawn with
ORTEP for Windows [42] at the 50% probability level, the overlay diagram was generated
by QMol [43] and the remaining crystallographic figures were drawn with DIAMOND using
arbitrary spheres [44]. Data manipulation and interpretation were with WinGX [40] and
PLATON [45].
4
4
.2. General procedure for the synthesis of 3a-f and 4a-r
.2.1. By conventional method (CON)
A mixture of substituted 2-methyl-3-acetylquinoline (1.0 mmol) and 5-chloro-3-methyl-1-
phenyl-1H-pyrazole-4-carbaldehyde or substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde
(
1.0 mmol) in ethanol (20 mL) containing 0.75 mmol of potassium hydroxide was stirred at
room temperature for 12 hours. The resulting mixture was neutralized with dilute acetic acid
and the precipitated solid was filtered, dried and purified by column chromatography using
ethyl acetate - hexane (1:1) to afford compounds 3a-f.
4.2.2. By ultrasonic method (US)
In a 50 mL Erlenmeyer flask, substituted 2-methyl-3-acetylquinoline (1.0 mmol) and 5-
chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde or substituted 1,3-diphenyl-1H-
pyrazole-4-carbaldehyde (1.0 mmol) were mixed in ethanol (20 mL) and 0.75 mmol of KOH
was added. The ultrasound probe was immersed directly in the reaction mixture. The
ultrasound generator emits the sound vibration into the reaction mixture for the period of 15
minutes. Sonication was achieved at frequencies of 22 kHz (amplitude of 50%). The reaction
mixture was maintained at room temperature by addition or removal of water from ultrasonic
bath. Sonication was continued until the starting material had disappeared as indicated by
TLC. On completion of the reaction, the reaction mixture was neutralized by dilute acetic
acid, the resultant solid was filtered, dried and purified by recrystallisation. The purity of the
ꢉꢁ
ꢁ

products was checked by TLC using mixture of ethyl acetate and hexane as mobile phase and
1
also by H NMR spectroscopy.
4
.2.3. Spectral and analytical details of the compounds synthesized by ultrasound assisted
method are given below
.2.3.1. 1-(6,8-dibromo-2-methylquinolin-3-yl)-3-(5-ethoxy-3-methyl-1-phenyl-1H-pyrazol-4-
4
yl)prop-2-en-1-one (3a)
1
mp 130–132 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 1.21-1.23 (t, J=7.0 Hz, 3H, -O-CH
-CH ), 7.17 (d,
), 7.53-7.55 (m,
H, Ar-H), 8.15 (s, 1H, Ar-H). 8.21 (s, 1H, Ar-H). 8.35 (s, 1H, Ar-H). Anal. calcd. for
: C, 54.08; H, 3.81; N, 7.57%, found: C, 54.35; H, 4.06; N, 7.22%.
.2.3.2 1-(2,4-dimethylquinolin-3-yl)-3-(5-ethoxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)prop-2-
en-1-one (3b)
mp 218–220 °C. H NMR (500 MHz, CDCl
.19 (s, 3H, -CH ), 2.50 (s, 3H, -CH ), 2.55 (s, 3H, -CH
CH -CH ), 7.43-7.945 (m, 3H, Ar-H), 7.48-7.51 (m, 2H, Ar-H), 7.55-7.58 (m, 2H, Ar-H),
.72-7.75 (m, 2H, Ar-H), 7.97 (d, J=8.0 Hz, 1H, Ar-H), 8.02 (d, J=8.0 Hz, 1H, Ar-H). Anal.
calcd. for C26 : C, 75.89; H, 6.12; N, 10.21%, found: C, 75.98; H, 6.50; N, 10.63%.
.2.3.3. 3-(5-ethoxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-1-(2-methyl-4-phenylquinolin-3-
2 3
-CH ),
2
.34 (s, 3H, -CH
3
), 2.79 (s, 3H, -CH
3
), 3.55-3.57 (q, J=7.0 Hz, 2H, -O-CH
2
3
J=16.5 Hz, 1H, H
α
), 7.43-7.949 (m, 2H, Ar-H), 7.50 (d, J=16.5 Hz, 1H, H
β
3
25 2 3 2
C H21Br N O
4
1
3
) ꢀ: 1.12-1.14 (t, J=7.0 Hz, 3H, -O-CH
2 3
-CH ),
2
3
3
3
), 3.74-3.79 (q, J=7.0 Hz, 2H, -O-
2
3
7
25 3 2
H N O
4
yl)prop-2-en-1-one (3c)
1
mp 126–128 °C. H NMR (400 MHz, CDCl
3
) ꢀ: 1.08-1.11 (t, J=7.0 Hz, 3H, -O-CH
-CH ), 6.40 (d,
), 7.31-7.35 (m, 3H, Ar-H), 7.39-7.48 (m, 6H,
Ar-H), 7.59-7.66 (m, 3H, Ar-H), 7.73-7.77 (m, 1H, Ar-H), 8.14 (d, J=8.0 Hz, 1H, Ar-H).
Anal. calcd. for C31 : C, 78.62; H, 5.75; N, 8.87%, found: C, 78.49; H, 5.59; N,
2 3
-CH ),
2
.18 (s, 3H, -CH
3
), 2.74 (s, 3H, -CH
3
), 3.74-3.79 (q, J=7.0 Hz, 2H, -O-CH
2
3
J=16.0 Hz, 1H, H
α
), 7.06 (d, J=16.0 Hz, 1H, H
β
27 3 2
H N O
8.64%.
4
.2.3.4.
1-(6-chloro-2-methyl-4-phenylquinolin-3-yl)-3-(5-ethoxy-3-methyl-1-phenyl-1H-
pyrazol-4-yl)prop-2-en-1-one (3d)
1
mp 160–162 °C. H NMR (400 MHz, CDCl
3
) ꢀ: 1.08-1.12 (t, J=7.0 Hz, 3H, -O-CH
-CH ), 6.39 (d,
), 7.30-7.33 (m, 3H, Ar-H), 7.41-7.48 (m, 5H,
Ar-H), 7.59-7.66 (m, 3H, Ar-H), 7.66-7.69 (m, 1H, Ar-H), 8.04 (d, J=8.0 Hz, 1H, Ar-H).
2 3
-CH ),
2
.17 (s, 3H, -CH
3
), 2.72 (s, 3H, -CH
3
), 3.74-3.79 (q, J=7.0 Hz, 2H, -O-CH
2
3
J=16.5 Hz, 1H, H
α
), 7.05 (d, J=16.5 Hz, 1H, H
β
ꢀ
ꢊꢁ
ꢁ

3 2
Anal. calcd. for C31H26ClN O : C, 73.29; H, 5.16; N, 8.27%, found: C, 73.12; H, 5.09; N,
8.06%.
4
.2.3.5.
3-(5-ethoxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-1-(2-methyl-6-nitro-4-
phenylquinolin-3-yl)prop-2-en-1-one (3e)
0
1
mp 172–174 C. H NMR (500 MHz, CDCl
.28 (s, 3H, -CH ), 2.81 (s, 3H, -CH ), 3.78-3.81 (q, J=7.0 Hz, 2H, -O-CH
J=16.5 Hz, 1H, H ), 7.17 (d, J=16.5 Hz, 1H, H ), 7.34-7.39 (m, 3H, Ar-H), 7.42-7.53 (m, 5H,
Ar-H), 7.60-7.62 (m, 2H, Ar-H), 8.25 (d, J=9.0 Hz, 1H, Ar-H), 8.51 (d, J=9.0 Hz, 1H, Ar-
H), 8.62 (s, 1H, Ar-H). Anal. calcd. for C31 : C, 71.80; H, 5.05; N, 10.80%, found: C,
3
) ꢀ: 1.11-1.14 (t, J=7.0 Hz, 3H, -O-CH
2 3
-CH ),
2
3
3
2
-CH ), 6.49 (d,
3
α
β
26 4 4
H N O
7
2.02; H, 5.35; N, 10.64%.
.2.3.6. 1-(6-chloro-4-(2-chlorophenyl)-2-methylquinolin-3-yl)-3-(5-ethoxy-3-methyl-1-
4
phenyl-1H-pyrazol-4-yl)prop-2-en-1-one (3f)
0
1
mp 118–120 C. H NMR (400 MHz, CDCl
.16 (s, 3H, -CH ), 2.72 (s, 3H, -CH ), 3.80-3.85 (q, J=7.0 Hz, 2H, -O-CH
J=16.0 Hz, 1H, H ), 7.21 (d, J=16.0 Hz, 1H, H ), 7.29-7.33 (m, 2H, Ar-H), 7.38-7.43 (m, 3H,
Ar-H), 7.45-7.50 (m, 4H, Ar-H), 7.63 (d, J=9.0 Hz, 1H, Ar-H), 7.68 (d, J=9.0 Hz, 1H, Ar-H),
.07 (d, J=9.0 Hz, 1H, Ar-H). Anal. calcd. for C31 : C, 68.64; H, 4.65; N, 7.75%,
found: C, 68.88; H, 4.80; N, 7.70%.
.2.3.7. 1-(6,8-dibromo-2-methylquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-
one (4a)
mp 189-191 °C. H NMR (500 MHz, CDCl
), 7.41-7.45 (m, 4H, Ar-H), 7.51-7.54 (m, 2H, Ar-H), 7.62-7.65 (m, 3H, Ar-H), 7.80 (d,
J=8.0 Hz, 2H, Ar-H). 7.97 (s, 1H, Ar-H). 8.12 (s, 1H, Ar-H), 8.21 (s, 1H, Ar-H). 8.36 (s,
3
) ꢀ: 1.11-1.13 (t, J=7.0 Hz, 3H, -O-CH
2 3
-CH ),
2
3
3
2
-CH ), 6.53 (d,
3
α
β
8
2 3 2
H25Cl N O
4
1
3
3
) ꢀ: 2.87 (s, 3H, -CH ), 7.01 (d, 16.0 Hz, 1H,
H
α
1
3
4
H, Ar-H). Anal. calcd. for C28
2 3
H19Br N O: C, 58.66; H, 3.34; N, 7.33%, found: C, 58.92; H,
.49; N, 7.26%.
.2.3.8. 1-(2,4-dimethylquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-one (4b)
1
mp 122-124 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.60 (s, 3H, -CH
), 7.30-7.38 (m, 4H, Ar-H), 7.45-7.50 (m, 4H, Ar-H), 7.55-7.59 (m, 2H,
Ar-H), 7.72-7.77 (m, 3H, Ar-H), 8.0 (d, J=8.0 Hz, 1H, Ar-H), 8.04 (d, J=8.0 Hz, 1H, Ar-H),
3 3
), 2.64 (s, 3H, -CH ), 6.85
(
d, 16.0 Hz, 1H, H
α
8
8
4
.29 (s, 1H, Ar-H). Anal. calcd. for C29
23 3
H N O: C, 81.09; H,5.40; N, 9.78%, found: C,
0.79; H, 5.39; N, 10.26%.
.2.3.9. 3-(1,3-diphenyl-1H-pyrazol-4-yl)-1-(2-methyl-4-phenylquinolin-3-yl)prop-2-en-1-one
(4c)
ꢀ
ꢀꢁ
ꢁ

1
mp 129-131 °C. H NMR (500 MHz, CDCl
), 7.19 (d, J=16.5 Hz, 1H, H ), 7.29-7.30 (m, 3H, Ar-H), 7.36-7.38 (m, 4H, Ar-H), 7.43-
.46 (m, 5H, Ar-H), 7.47-7.50 (m, 4H, Ar-H), 7.62 (d, J=7.5 Hz, 1H, Ar-H), 7.72 (d, J=7.5
Hz, 1H, Ar-H), 8.07 (s, 1H, Ar-H), 8.11 (d, J=9.0 Hz, 1H, Ar-H). Anal. calcd. for
O: C, 83.07; H,5.13; N, 8.55%, found: C, 82.29; H, 5.32; N, 8.67%.
3 3
) ꢀ: 2.74 (s, 3H, -CH ), 6.44 (d, 16.5 Hz, 1H,
H
α
β
7
34 25 3
C H N
4
2
.2.3.10. 1-(6-chloro-2-methyl-4-phenylquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-
-en-1-one (4d)
1
mp 157-159 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.72 (s, 3H, -CH
), 7.26-7.28 (m, 2H, Ar-H), 7.36-7.39 (m, 4H, Ar-H), 7.44-
.51 (m, 7H, Ar-H), 7.58 (d, J=2.0 Hz, 1H, Ar-H), 7.68-7.70 (dd, J=7.0 Hz & 2.0 Hz, 2H, Ar-
H), 7.72 (d, J=7.0 Hz, 1H, Ar-H), 8.04 (d, J=9.0 Hz, 1H, Ar-H). 8.07 (s, 1H, Ar-H), Anal.
3
), 6.43 (d, 16.5 Hz, 1H,
H
α
), 7.17 (d, J=16.5 Hz, 1H, H
β
7
calcd. for C34
3
H24ClN O: C, 77.63; H, 4.60; N, 7.99%, found: C, 77.82; H, 4.76; N, 8.27%.
4.2.3.11. 3-(1,3-diphenyl-1H-pyrazol-4-yl)-1-(2-methyl-6-nitro-4-phenylquinolin-3-yl)prop-2-
en-1-one (4e)
1
mp 132-134 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.78 (s, 3H, -CH
), 7.29-7.30 (m, 2H, Ar-H), 7.37-7.39 (m, 4H, Ar-H), 7.43-
.45 (m, 2H, Ar-H), 7.49-7.51 (m, 5H, Ar-H), 7.72 (d, J=8.0 Hz, 2H, Ar-H), 8.09 (s, 1H, Ar-
H), 8.22 (d, J=9.0 Hz, 1H, Ar-H), 8.52 (d, J=9.0 Hz, 1H, Ar-H), 8.58 (s, 1H, Ar-H). Anal.
calcd. for C34 : C, 76.11; H, 4.51; N, 10.44%, found: C, 75.96; H, 4.39; N, 10.26%.
.2.3.12. 1-(6-chloro-4-(2-chlorophenyl)-2-methylquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-
3
), 6.44 (d, 16.0 Hz, 1H,
H
α
), 7.18 (d, J=16.0 Hz, 1H, H
β
7
24 4 3
H N O
4
4
-yl)prop-2-en-1-one (4f)
1
mp 124-126 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.76 (s, 3H, -CH
3
), 6.53 (d, 16.0 Hz, 1H,
α
H ), 6.90 (d, J=8.4 Hz, 2H, Ar-H), 7.23 (dd, J=7.5 Hz, 1H, Ar-H), 7.29 (d, J=2.5 Hz, 1H, Ar-
H), 7.37-7.43 (m, 5H, Ar-H), 7.47-7.52 (m, 5H, Ar-H), 7.68 (dd, J=9.0 Hz & 2.5 Hz, 1H, Ar-
H) 7.74 (d, J=8.0 Hz, 2H, Ar-H), 8.06 (d, J=9.0 Hz, 1H, Ar-H), 8.13 (s, 1H, Ar-H). Anal.
calcd. for C34
H23Cl
2
3
N O2: C, 72.86; H, 4.14; N, 7.50%, found: C, 72.62; H, 3.99; N, 7.25%.
4
3
.2.3.13. 3-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(6,8-dibromo-2-methylquinolin-
-yl)prop-2-en-1-one (4g)
1
mp 205-207 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.88 (s, 3H, -CH
3
), 7.02 (d, 16.5 Hz, 1H,
H
α
), 7.39-7.42 (m, 1H, Ar-H), 7.51-7.54 (m, 4H, Ar-H), 7.59-7.62 (m, 4H, Ar-H), 7.78 (d,
J=8.0 Hz, 1H, Ar-H), 7.98 (s, 1H, Ar-H), 8.12 (s, 1H, Ar-H), 8.22 (s, 1H, Ar-H), 8.35 (s, 1H,
Ar-H). Anal. calcd. for C28
N, 6.56%.
3 3
H18Br N O: C, 51.57; H, 2.78; N, 6.44%, found: C, 51.32; H, 2.99;
ꢀ
ꢂꢁ
ꢁ

4.2.3.14.
3-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(2,4-dimethylquinolin-3-
yl)prop-2-en-1-one (4h)
1
mp 163-165 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.59 (s, 3H, -CH
), 7.34-7.38 (m, 3H, Ar-H), 7.43-7.51 (m,
H, Ar-H), 7.58-7.61 (m, 1H, Ar-H), 7.72-7.77 (m, 3H, Ar-H), 7.99 (d, J=8.0 Hz, 1H, Ar-H),
.04 (d, J=8.0 Hz, 1H, Ar-H), 8.27 (s, 1H, Ar-H). Anal. calcd. for C29 O: C, 68.51;
3 3
), 2.64 (s, 3H, -CH ), 6.84
(
d, 16.5 Hz, 1H, H
α
), 7.24 (d, J=16.5 Hz, 1H, H
β
4
8
H22BrN
3
H, 4.36; N, 8.27%, found: C, 68.76; H, 4.59; N, 8.52%.
.2.3.15 3-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(2-methyl-4-phenylquinolin-3-
4
yl)prop-2-en-1-one (4i)
1
mp 200-202 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.72 (s, 3H, -CH
3
), 6.38 (d, 16.0 Hz, 1H,
H
α
β
), 7.11 (d, J=16.0 Hz, 1H, H ), 7.29-7.30 (m, 4H, Ar-H), 7.32-7.38 (m, 2H, Ar-H), 7.43-
7
.49 (m, 7H, Ar-H), 7.61 (dd, J=9.0 Hz & 2.5 Hz, 1H, Ar-H) 7.68 (d, J=8.0 Hz, 2H, Ar-H),
.74-7.77 (m, 1H, Ar-H), 8.01 (s, 1H, Ar-H), 8.10 (d, J=8.0 Hz, 1H, Ar-H). Anal. calcd. for
7
C
34
H
24BrN
3
O: C, 71.58; H, 4.24; N, 7.37%, found: C, 71.32; H, 4.12; N, 7.16%.
4.2.3.16.
3-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(6-chloro-2-methyl-4
phenylquinolin-3-yl)prop-2-en-1-one (4j)
1
mp 129-131 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.72 (s, 3H, -CH
3
), 6.40 (d, 16.0 Hz, 1H,
H
α
), 7.13 (d, J=16.0 Hz, 1H, H
.50 (m, 3H, Ar-H), 7.52 (d, J=2.5 Hz, 1H, Ar-H), 7.54-7.77 (m, 3H, Ar-H), 7.64 (d, J=7.0
Hz, 1H, Ar-H), 7.77 (d, J=7.0 Hz, 1H, Ar-H), 8.02 (d, J=9.0 Hz, 1H, Ar-H). 8.06 (s, 1H, Ar-
β
), 7.29-7.35 (m, 3H, Ar-H), 7.36-7.41 (m, 4H, Ar-H), 7.45-
7
3
H). Anal. calcd. for C34H23BrClN O: C, 67.51; H, 3.83; N, 6.95%, found: C, 67.74; H, 3.95;
N, 7.06%.
4
.2.3.17.
3-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(2-methyl-6-nitro-4-
phenylquinolin-3-yl)prop-2-en-1-one (4k)
1
mp 184-186 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.78 (s, 3H, -CH
3
), 6.42 (d, 16.0 Hz, 1H,
H
α
), 7.15 (d, J=16.0 Hz, 1H, H
.53 (m, 7H, Ar-H), 7.69 (d, J=8.0 Hz, 2H, Ar-H), 8.06 (s, 1H, Ar-H), 8.24 (d, J=9.0 Hz, 1H,
Ar-H), 8.52 (d, J=9.0 Hz, 1H, Ar-H), 8.59 (s, 1H, Ar-H). Anal. calcd. for C34 : C,
β
), 7.30-7.32 (m, 4H, Ar-H), 7.36-7.39 (m, 1H, Ar-H), 7.48-
7
4 3
H23BrN O
66.35; H, 3.77; N, 9.10%, found: C, 66.22; H, 3.59; N, 8.92%.
4
.2.3.18. 3-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(6-chloro-4-(2-chlorophenyl)-2-
methylquinolin-3-yl)prop-2-en-1-one (4l)
1
mp 190-192 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.75 (s, 3H, -CH
3
), 6.52 (d, 16.0 Hz, 1H,
H
α
), 7.24 (dd, J=7.5 Hz & 2.0 Hz, 1H, Ar-H), 7.30 (d, J=2.5 Hz, 1H, Ar-H), 7.35-7.43 (m,
ꢀ
ꢃꢁ
ꢁ

5H, Ar-H), 7.47-7.52 (m, 6H, Ar-H), 7.69 (d, J=9.0 Hz, 1H, Ar-H) 7.72 (d, J=8.0 Hz, 2H, Ar-
H), 8.08 (d, J=9.0 Hz, 1H, Ar-H), 8.11 (s, 1H, Ar-H). Anal. calcd. for C34 O: C,
H
2 3
22BrCl N
63.87; H, 3.47; N, 6.57%, found: C, 64.20; H, 3.22; N, 6.90%.
4
.2.3.19. 1-(6,8-dibromo-2-methylquinolin-3-yl)-3-(3-(4-methoxyphenyl)-1-phenyl-1H-
pyrazol-4-yl)prop-2-en-1-one (4m)
1
mp 133-135 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.86 (s, 3H, -CH
3
), 3.88 (s, 3H, -OCH
3
),
7
.04 (d, 16.0 Hz, 1H, H
α
), 7.36-7.42 (m, 3H, Ar-H), 7.48-7.55 (m, 4H, Ar-H), 7.61-7.65 (m,
2H, Ar-H), 7.81 (d, J=8.0 Hz, 1H, Ar-H), 7.98 (s, 1H, Ar-H), 8.10 (s, 1H, Ar-H), 8.23 (s, 1H,
Ar-H), 8.34 (s, 1H, Ar-H). Anal. calcd. for C29
found: C, 57.90; H, 3.75; N, 7.24%.
2 3
H21Br N O: C, 57.73; H, 3.51; N, 6.96%,
4.2.3.20.
1-(2,4-dimethylquinolin-3-yl)-3-(3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-4-
yl)prop-2-en-1-one (4n)
1
mp 127-129 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.61 (s, 3H, -CH
), 7.37-7.39 (m, 3H, Ar-H), 7.47-7.59 (m,
H, Ar-H), 7.68-7.78 (m, 5H, Ar-H), 7.98 (d, J=8.0 Hz, 1H, Ar-H), 8.01-8.07 (m, 2H, Ar-H),
3 3
), 2.65 (s, 3H, -CH ), 6.83
(
d, 16.0 Hz, 1H, H
α
), 7.29 (d, J=16.0 Hz, 1H, H
β
5
8
7
4
.29 (s, 1H, Ar-H). Anal. calcd. for C30
25 3 2
H N O : C, 78.41; H, 5.48; N, 9.14%, found: C,
8.62; H, 5.24; N, 8.80%.
.2.3.21. 3-(3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(2-methyl-4-phenylquinolin-3-
yl)prop-2-en-1-one (4o)
1
mp 190-192 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.74 (s, 3H, -CH
3
), 3.81 (s, 3H, -OCH
3
),
6
7
1
.43 (d, 16.5 Hz, 1H, H
α
), 6.87 (d, J=8.5 Hz, 2H, Ar-H), 7.17 (d, J=16.5 Hz, 1H, H
β
), 7.29-
.30 (m, 2H, Ar-H), 7.32-7.38 (m, 3H, Ar-H), 7.43-7.49 (m, 6H, Ar-H), 7.62 (d, J=9.0 Hz,
H, Ar-H) 7.70 (d, J=8.0 Hz, 2H, Ar-H), 7.74-7.77 (m, 1H, Ar-H), 8.04 (s, 1H, Ar-H), 8.12
(
27 3 2
d, J=8.0 Hz, 1H, Ar-H). Anal. calcd. for C35H N O : C, 80.59; H, 5.22; N, 8.06%, found: C,
8
0.32; H, 5.39; N, 8.26%.
.2.3.22. 1-(6-chloro-2-methyl-4-phenylquinolin-3-yl)-3-(3-(4-methoxyphenyl)-1-phenyl-1H-
4
pyrazol-4-yl)prop-2-en-1-one (4p)
1
mp 98-100 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.72 (s, 3H, -CH
3
), 3.83 (s, 3H, -OCH
), 7.26-7.28
m, 2H, Ar-H), 7.35-7.38 (m, 3H, Ar-H), 7.45-7.50 (m, 5H, Ar-H),7.58 (d, J=8.0 Hz, 1H, Ar-
3
), 6.42
(
(
d, 16.5 Hz, 1H, H
α
), 6.89 (d, J=8.5 Hz, 2H, Ar-H), 7.16 (d, J=16.5 Hz, 1H, H
β
H), 7.68 (dd, J=7.0 Hz & 2.0 Hz, 1H, Ar-H) 7.70 (d, J=8.0 Hz, 2H, Ar-H), 8.05 (s, 1H, Ar-
H), 8.07 (d, J=8.0 Hz, 1H, Ar-H). Anal. calcd. for C35 : C, 75.60; H, 4.71; N,
H
3 2
26ClN O
7.56%, found: C, 75.32; H, 4.59; N, 7.46%.
ꢀ
ꢄꢁ
ꢁ

4.2.3.23.
3-(3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(2-methyl-6-nitro-4-
phenylquinolin-3-yl)prop-2-en-1-one (4q)
1
mp 142-144 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.79 (s, 3H, -CH
), 7.31-7.34 (m, 4H, Ar-H), 7.37-7.39
m, 2H, Ar-H), 7.50-7.53 (m, 6H, Ar-H), 7.70 (d, J=8.0 Hz, 2H, Ar-H), 8.04 (s, 1H, Ar-H),
.27 (d, J=9.0 Hz, 1H, Ar-H), 8.53 (d, J=9.0 Hz, 1H, Ar-H), 8.59 (s, 1H, Ar-H). Anal. calcd.
: C, 74.19; H, 4.63; N, 9.89%, found: C, 74.52; H, 4.79; N, 9.99%.
.2.3.24. 1-(6-chloro-4-(2-chlorophenyl)-2-methylquinolin-3-yl)-3-(3-(4-methoxyphenyl)-1-
3 3
), 3.87 (s, 3H, -OCH ),
6
.44 (d, 16.0 Hz, 1H, H
α
), 7.16 (d, J=16.0 Hz, 1H, H
β
(
8
26 4 4
for C35H N O
4
phenyl-1H-pyrazol-4-yl)prop-2-en-1-one (4r)
1
mp 110-112 °C. H NMR (500 MHz, CDCl
3
) ꢀ: 2.76 (s, 3H, -CH
3
), 3.83 (s, 3H, -OCH
3
),
6
.53 (d, 16.0 Hz, 1H, H
Ar-H), 7.29 (d, J=2.5 Hz, 1H, Ar-H), 7.35-7.42 (m, 6H, Ar-H), 7.49-7.51 (m, 3H, Ar-H), 7.68
dd, J=9.0 Hz & 2.0 Hz, 1H, Ar-H) 7.72 (d, J=8.0 Hz, 2H, Ar-H), 8.07 (d, J=9.0 Hz, 1H, Ar-
α
), 6.90 (d, J=8.5 Hz, 2H, Ar-H), 7.23 (dd, J=7.5 Hz & 2.0 Hz, 1H,
(
H), 8.11 (s, 1H, Ar-H). Anal. calcd. for C35
C, 71.32; H, 4.19; N, 7.36%.
2 3 2
H25Cl N O : C, 71.19; H, 4.27; N, 7.12%, found:
5. Conclusion
The synthesis of the title chalcones via the Claisen–Schmidt condensation leads to the
exclusive formation of the E-configuration, which is a result of the more favourable
antiperiplanar elimination of the hydroxide group from the carbanion intermediate in this
reaction, as established by spectroscopy and X-ray crystallography. The ultrasonic method of
synthesis provides significant benefits over the conventional methods with respect to yield,
reaction time and purity of the products. Some of the compounds exhibited promising anti-
microbial activity and the methoxy substituted compounds showed moderate antioxidant
activity.
Acknowledgements
PB and RP gratefully acknowledge Council of Scientific and Industrial Research (CSIR),
India for research grant 02(0076)/12/EMR-II and Senior Research Fellowship
(
09/919/(0014)/2012EMR-I), respectively. The Ministry of Higher Education (Malaysia) is
thanked for funding this research through the High-Impact Research scheme (UM.C/HIR-
MOHE/SC/03). The authors are thankful to the instrumental facilities provided by SAIFs at
IIT-Madras and IIT-Bombay, India.
ꢀ
ꢅꢁ
ꢁ

Appendix A. Supplementary material
CCDC-846063 and -846064 contain the supplementary crystallographic data for 3c and 4h,
respectively. These data can be obtained free of charge from the Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Supplementary data associated with
this article can be found, in the online version, at http://doi:xxxxxxxx.
ꢀ
ꢆꢁ
ꢁ

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ꢂꢊꢁ
ꢁ

Scheme and Figure Captions:
Scheme 1. Synthetic scheme of pyrazolyl-quinolinyl chalcone derivatives, 3a-f and 4a-r.
Fig. 1. Molecular structure of pyrazolyl-quinolinyl chalcone derivatives.
Fig. 2. Two canonical forms of generic E-chalcone.
1
Fig. 3. H NMR spectrum of compound 3c.
1
Fig. 4. H NMR spectrum of (a) 4g showing the position of H
5
and H
7
protons between 8.0 to
8.4 ppm; and (b) 4k showing the position of H
5
, H
7
and H
8
protons between 8.2 to 8.7 ppm.
Fig. 5. Molecular structure of 3c showing atomic labelling scheme.
Fig. 6. Molecular structure of 4h showing atomic labelling scheme. The water molecule of
salvation has been excluded.
Fig. 7. Overlay diagram of molecules of 3c (red image) and 4h (blue) with the pyrazolyl rings
overlapped.
ꢂꢀꢁ
ꢁ

ꢁ
Fig. 1. Molecular structure of pyrazolyl-quinolinyl chalcone derivatives.
ꢁ
ꢁ
ꢁ
Fig. 2. Two canonical forms of (E)-Chalcone.
ꢁ
ꢁ
1
Fig. 3. H NMR spectrum of compound 3c.
ꢂꢂꢁ
ꢁ

(
a)
ꢁ
(b)
1
Fig. 4. H NMR spectrum of (a) compound 4g showing the position of H
5
and H
and H
7
protons
8
protons
between 8.0 to 8.4 ppm (b) compound 4k showing the position of H
5
, H
7
between 8.2 to 8.7 ppm.
ꢁ
ꢂꢃꢁ
ꢁ

ꢁ
Fig. 5. Molecular structure of 3c showing atomic labelling scheme.
ꢁ
ꢁ
ꢁ
Fig. 6. Molecular structure of 4h showing atomic labelling scheme.
ꢁ
ꢁ
ꢂꢄꢁ
ꢁ

ꢁ
Fig. 7. Overlay diagram of molecules of 3c (red image) and 4h (blue) with the pyrazolyl rings
overlapped.
ꢁ
ꢁ
Scheme. 1. Synthetic scheme of pyrazolyl-quinolinyl chalcone derivatives, 3a-f and 4a-r.
ꢂꢅꢁ
ꢁ

Table 1. Details of synthesis of pyrazolyl-quinoline chalcones 3a-f and 4a-r under
conventional and ultrasonic methods.
Compd
Starting materials
Substitution
CON
US
%
Yield
% Yield
R
1
R
2
R
3
R
4
3
3
a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
1c
1d
1d
1d
1d
1d
1d
2a
2b
2c
2d
2e
2f
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
H
Br
H
Br
H
H
H
H
H
Br
H
H
H
H
H
Br
H
H
H
H
H
Br
H
H
H
H
H
56
50
60
63
61
60
76
70
69
72
79
76
72
71
76
70
69
66
70
78
66
69
73
71
76
78
79
82
84
85
90
87
83
91
94
90
86
82
93
81
90
89
85
87
86
90
93
91
b
CH
3
3
c
C
6
C
6
C
6
H
5
5
5
H
3
d
H
H
Cl
NO
Cl
Br
H
3
e
2
3
f
2-ClC
H
6
H
4
4
4
a
2a
2b
2c
2d
2e
2f
C
C
C
C
C
C
6
6
6
6
6
6
H
5
5
5
5
5
5
b
H
H
H
H
H
CH
3
4
c
C
6
C
6
C
6
H
5
H
4
d
H
H
5
5
Cl
NO
Cl
Br
H
4
e
2
2
2
4
f
2-ClC
6
H
4
4
4
4
4
g
2a
2b
2c
2d
2e
2f
C
C
C
C
C
C
6
6
6
6
6
6
4
H 4-Br
4
H 4-Br
4
H 4-Br
4
H 4-Br
4
H 4-Br
4
H 4-Br
H
h
CH
3
4
i
C
6
C
6
C
6
H
5
H
4
j
H
H
5
5
Cl
NO
Cl
Br
H
4
k
4
l
2-ClC
6
H
4
m
2a
2b
2c
2d
2e
2f
C
C
C
C
C
C
6
H
6
H
6
H
6
H
6
H
6
H
4
4-OCH
4
4-OCH
4
4-OCH
4
4-OCH
4
4-OCH
4
4-OCH
3
3
3
3
3
3
H
4
n
o
p
q
CH
3
4
C
6
C
6
C
6
H
5
H
4
4
H
H
5
5
Cl
NO
Cl
4
r
6
2-ClC H
ꢁ
Table 2. Effect of different catalysts (in the substrate to catalyst ratio 1:0.75) on the yield of
chalcones 3a (entries 1-4) and 4a (entries 5-8).
ꢂꢆꢁ
ꢁ

Entry Catalyst Time Yield
(
min)
45
(%)
40
76
61
53
45
90
66
59
1
2
3
4
5
6
7
8
2 3
K CO
KOH
NaOH
EtONa
15
30
30
K CO
2
3
45
KOH
NaOH
EtONa
15
30
30
ꢁ
Table 3. Spectral data for the synthesized pyrazolyl-quinolinyl chalcones 3a-f and 4a-r.
1
Comp
Absorbance
max, nm (ε×10 )
H NMR (δ, ppm)
Mass
[M+H]
FT-IR
-4
+
-1
-1
λ
δH
α
δH
β
J
HαHβ(Hz)
16.5
b
ν
C=O(cm )
ν
C=C(cm )
3a
247(4.92), 331(4.33)
232(5.15), 319(4.25)
234(4.62), 332(4.48)
231(4.88), 334(4.54)
232(4.73), 262(4.77), 322(4.65)
233(4.85), 332(4.50)
231(4.91), 261(4.79), 347(4.53)
231(4.88), 275(4.55), 341(4.37)
230(5.00), 272(4.76), 337(4.62)
232(5.06), 273(4.74), 338(4.63)
229(4.61), 274(4.69), 349(4.35)
231(5.01), 270(4.73), 340(4.59)
230(4.88), 274 (4.76), 345(4.50)
231(5.02), 276(4.81), 335(4.66)
231(4.51), 277(4.29), 339(4.06)
234(4.93), 278(4.67), 332(4.20)
229(4.78), 271(4.88), 340(4.61)
232(5.05), 277(4.79), 338(4.61)
7.17 7.50
555.1
412.1
474.1
508.1
519.2
542.1
474.1
430.2
492.2
526.1
537.2
560.1
653.8
508.1
570.1
606.1
615.1
640.1
1665
1650
1662
1654
1673
1662
1659
1672
1669
1650
1653
1680
1671
1644
1682
1670
1662
1671
1604
1590
1580
1611
1602
1598
1601
1625
1603
1591
1611
1613
1600
1560
1601
1594
1602
1569
3b
a
a
3
c
6.40 7.06
6.39 7.05
6.49 7.17
6.53 7.21
7.01
6.85
6.44 7.19
6.43 7.17
6.44 7.18
6.53
7.02
16.0
16.5
16.5
16.0
16.0
16.0
16.5
16.5
16.0
16.0
16.5
16.5
16.0
16.0
16.0
16.0
3
d
3
e
3
f
4a
a
a
4
b
4
c
4
d
4
e
4
f
a
a
4g
4
h
6.84 7.24
6.38 7.11
6.40 7.13
6.42 7.15
4i
4
j
4
k
4l
6.52
a
ꢂꢇꢁ
ꢁ

4
4
4
4
4
4
m
n
o
p
q
244(4.85), 282(4.63)
7.04
a
16.0
16.0
16.5
16.5
16.0
16.0
604.0
460.1
522.1
556.1
567.1
590.1
1657
1662
1679
1659
1660
1666
1606
1600
1609
1598
1596
1625
232(4.74), 282(4.58),342(4.20)
230(4.91), 281(4.73),344(4.47)
232(4.94), 282(4.72), 340(4.44)
229(4.68), 269(4.77),341(4.49)
231(4.99), 280(4.78), 347(4.48)
6.83 7.29
6.43 7.17
6.42 7.16
6.44 7.16
r
6.53
a
a
The NMR signal for this proton was obscured by the overlapping signals in the aromatic region.
The JHαHβ(Hz) value could not be determined owing to the overlapping of signals in the aromatic region.
b
Table 4. Crystallographic and refinement details for compounds 3c and 4h.
Crystal data
Empirical formula
Formula weight
Crystal colour
Crystal dimensions (mm)
Crystal system
Space group
a (Å)
3c
4h
C
31
H
27
N
3
O
2
29 3 2
C H22BrN O.H O
473.56
Colourless
526.42
Colourless
0.35 x 0.35 x 0.35
triclinic
0.05 x 0.05 x 0.25
triclinic
P¯1
P¯1
9.5255(9)
11.3511(12)
13.5671(12)
111.562(9)
8.3660(4)
12.3776(7)
13.3710(8)
116.152(6)
b (Å)
c (Å)
α(º)
β(º)
γ(º)
103.358(8)
99.823(8)
94.385(4)
99.929(4)
3
V Å
1273.4(2)
2
1205.89(11)
Z
2
-
3
D
x
(g cm )
F(000)
μ(Mo Kα) (mm )
1.235
500
1.450
540
-
1
0.078
-
1
μ(Cu Kα) (mm )
2.579
8220
0.020
4761
4609
Reflections collected
8720
0.052
4491
2868
R
int
Unique reflections
Obs. reflections [I > 2 σ( I)]
R [obs. reflns]
0.056
0.060
a, b in weighting scheme
wR (all data)
0.036, 0.233
0.130
0.074, 2.891
0.158
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Table 5. In vitro antioxidant activity of compounds 4m-r. (DPPH Method)
Compounds
%DPPH
25.50±0.23
4
4
4
4
4
4
m
n
o
p
q
r
20.25±0.10
27.64±0.30
22.20±0.19
32.24±0.12
19.60±0.25
67.50±0.50
BHA
BHA-Standard substance
±
- Standard deviation
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Table 6. Anti-microbial activity of compounds 3a-f and 4a-r.
Comp
Zone of inhibition (mm)
Bacterial strains
Fungal strains
C.albicans A.niger
E.coli
P.aeruginosa
S.aureus
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