An efficient solvent-free synthesis of 3-acetyl-4-arylquinoline-based enaminones and its derivatives using DMFDMA reagent

Article abstract of DOI:10.1007/s11696-017-0375-5

Abstract: A series of 3-substituted-4-arylquinoline derivatives were synthesized using 3-acetyl-4-arylquinoline. The acetyl function of 3-acetyl-4-arylquinoline was successfully converted into its corresponding enaminone using DMFDMA as a reagent which in

Full text of DOI:10.1007/s11696-017-0375-5

Chemical Papers
https://doi.org/10.1007/s11696-017-0375-5
ORIGINAL PAPER
An efcient solvent‑free synthesis of 3‑acetyl‑4‑arylquinoline‑based
enaminones and its derivatives using DMFDMA reagent
L. Jyothish Kumar1 · V. Vijayakumar1
Received: 22 July 2017 / Accepted: 21 December 2017
© Institute of Chemistry, Slovak Academy of Sciences 2018
Abstract
A series of 3-substituted-4-arylquinoline derivatives were synthesized using 3-acetyl-4-arylquinoline. The acetyl function of
3-acetyl-4-arylquinoline was successfully converted into its corresponding enaminone using DMFDMA as a reagent which
in turn successfully converted into pyrazole, isoxazole, pyrimidine, phenyl aminoprop-2-en-1-one, pyridin-2-yl-amino-
prop-2-en-1-one, 2-methylpyridine-3-carboxylate by treating with reagents such as hydrazine, hydroxylamine, guanidine
hydrochloride, aniline, 2-amino pyridine, ethyl acetoacetate, respectively, under solvent-free microwave irradiation as well
as under the conventional thermal heating processes. All the synthesized compounds were found to be obtained in better
yields under the microwave irradiation over the conventional process.
Electronic supplementary material The online version of this
article (doi:https://doi.org/10.1007/s11696-017-0375-5) contains
supplementary material, which is available to authorized users.
* V. Vijayakumar
kvpsvijayakumar@gmail.com
1
Centre for Organic and Medicinal Chemistry, School
of Advanced Sciences, VIT University, Vellore 632 014,
Tamil Nadu, India
Vol.:(0123456789)
1 3

Chemical Papers
Graphical abstract
NH
Y
N
X
O
Y
O
4aN-c
N
O
Y
X
N
X
EtOH
a
O
NH2NH2
O d
N
7a-c
l
N
5a-c
C
H
.
H
N
O
H
H2
N
4 O
O
A
D
H
tO
E
c
M
F
O
b
Y
X
N
c
N
2
H
N
3a-c
H
N
H
C
NH2
2
H
N
F
M
D
Y
N
N
DMFDMA in Toluene
Reflux
X
N
6a-c
Y
O
O
O
Y
H
S. No
X
X
Y
H
1a-7a
X
1b-7b Cl
1c-7c Cl
EtOH
o-phospharic acid
H
O
N
2a-c
Cl
NH2
1a-c
Reagents and conditions:
a, b = Reflux in Ethanol(EtOH), 6 hrs
c = Reflux in DMF, 6 hrs
d = Ammoniun acetate, K2CO3, DMF, reflux, 5 hrs
Keywords DMFDMA · Enaminones · Microwave irradiation · Solvent-free conditions
synthetic chemistry by the construction of various organic
compounds (Wan et al. 2016b , 2015a ) especially in the
synthesis of wide variety of biologically active heterocycles
(Wan et al. 2014, 2015b , Abu-Shanab et al. 2009, 2003),
enaminones with electron-defcient amines, exhibiting the
extensive applications in organic syntheses (Wan et al.
2016c).
Introduction
DMFDMA is one of the important synthetic reagents in
organic synthesis due to its higher reactivity (Abu-Shanab
et al. 2009). Literature references (Abu-Shanab et al. 2009;
Elassar and El-Khair 2003; Mabkhot et al. 2011) empha-
sized several methods in which formamide acetal had been
reported. Enaminones are obtained by treating the com-
pounds with keto functions and DMFDMA have proved to
be very useful intermediate (Abu-Shanab et al. 2009; Kumar
et al. 2012, Borah et al. 2015; Abu-Shanab et al. 2009,
2003, Y. Liu et al. 2013) as well as useful building blocks
in the organic synthesis with enriched structural diversity
(Wan et al. 2016a) and displayed numerous applications in
On the other hand, the quinolines are often used to design
and synthesize the compounds with various pharmacologi-
cal properties such as antimicrobial (Rao et al. 2017), anti-
protozoal (Fakhfakh et al. 2003), anti-infammatory (Bekhit
et al. 2004) anticancer (Kalita et al. 2015) and anti-tubercu-
lar activity (Rao et al. 2017; Vangapandu et al. 2004; Nay-
yar et al. 2006; Venkatesham et al. 2013). The synthesis of
1 3

Chemical Papers
enaminone and its derivatives from simple ketones using
DMFDMA are available in the literature (Kumar et al. 2012;
Mabkhot et al. 2011; Djung et al. 2011, El-Kateb et al.
2012; Pleier et al. 2001; Rosa et al. 2008; Arioli et al. 2011;
Ldehna et al. 2015; Prasanna et al. 2014; Cao et al. 2015).
This prompted us to attempt the present work in which
we have used the 3-acetyl-2-methyl-4-arylquinoline to syn-
thesize corresponding enaminone which in turn is used as a
synthon to obtain corresponding pyrazole, isoxazole, pyrim-
idine, phenylamino-prop-2-en-1-one, (pyridin-2-yl-amino)
prop-2-en-1-one and 2-methylpyridine-3-carboxylates using
hydrazine, hydroxylamine, guanidine hydrochloride, aniline,
2-amino pyridine, ethylacetoacetate, respectively, by adopt-
ing conventional procedure in the presence of solvents and
also via solvent-free microwave-assisted reactions. In gen-
eral, improvement in yields and reduction in reaction time
were observed when the reactions were carried out under
microwave irradiation compared with conventional method.
Results and discussion
Chemistry
In the present work, a series of 3-acetyl-4-arylquinoline-
based enaminones were synthesized by the conventional and
microwave-assisted synthesis methodology. In the frst step,
diferent benzophenone derivatives (1a–c) were converted
into 3-acetyl-4-aryl quinolines (Sarveswari and Vijaya-
kumar 2012) (2a–c) by treating them with acetyl acetone
(Scheme 1) in ethanol in the presence of ortho-phosphoric
acid (catalyst). The obtained products (2a–c) were fur-
ther treated with DMFDMA reagent to form correspond-
ing enaminone compounds (3a–c) under the conventional
method, in which diferent solvents such as dimethylforma-
mide, xylene, toluene, acetonitrile and dioxane were exam-
ined for the efective conversion of 2a–c to 3a–c (Scheme 1).
Out of which, in toluene the yield was observed to be bet-
ter and hence, toluene was considered as a suitable solvent
for this reaction (Table 1). The same conversion was also
attempted under the microwave irradiation with 240 W
power level. These results are compared with the conven-
tional synthetic procedure in Table 2 which revealed that
the conversion of 2a–c to 3a–c efected efciently under
Scheme 1 Synthesis of
3-acetyl-4-phenylquinoline
derivatives
NH
N
Y
O
X
Y
O
X
N
N
4a-c
N
O
Y
N
7a-c
Ethanol
NH2NH2
C
a
H
X
3
C
C
C
O
d
H
3
C
H
2
N
5a-c
O
C
D
b
h
O
O
l
M
l
o
n
O
O
C
N
a
F
H
.
C
2
t
H
H
E
N
Y
O
H
5
4
2
H
X
N
N
3a-c
H
c
N
C
H
N
/
F
NH2
N
3
O
H
C
DMFDMA
K
2
2
H
N
M
Toluene reflux
Y
N
D
X
Y
N
6a-c
O
O
Y
O
X
X
O
Ethanol
o-Phosphoric acid
S.No
X
Y
H
H
NH2
1a-7a
H
N
1a-c
1b-7b Cl
2a-c
1c-7c Cl Cl
Reagents and Conditions
a,b: Refluxin Ethanol for 6 hrs; c: Reflux in DMF for 6 hrs
d: Reflux in DMF for 5 hrs
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Chemical Papers
Table 1 Optimization for the synthesis of 3-acetyl-4-phenylquinoline-
microwave irradiation method with better yield with less
reaction duration. All the newly formed enaminones 3a–c
were characterized using 1H-NMR, 13C-NMR, DEPT-135,
based enaminones
S. no.
Solvents
T (°C)
Time (h)
Yield (%)
1
1H, H-COSY, HSQC, HRMS (ESI) and the detailed data
1
2
3
4
5
6
7
DMF
DMF
DMF
Xylene
Toluene
Acetonitrile
Dioxane
90
14
12
8
6
6
48
36
20
28
47
78
85
15
10
are included in the experimental part.
100
> 110
120
110
90
The compound 3b was grown as single crystal in ethyl
acetate and toluene (1:1) mixture and subjected to single-
crystal X-ray difraction studies and the ORTEP of 3b is
given as Fig. 1 (CCDC no: 1518424). The above enaminones
(3a–c) aford various 4-phenylquinoline derivatives such as
4a–c, 5a–c, 6a–c and 7a–c (Scheme 1) when treated with
reagents such as hydrazine, hydroxylamine hydrochloride,
guanidine hydrochloride, ethylacetoacetate, respectively,
whereas the corresponding substituted products such as 8a–c
and 9a–c (Scheme 2) were found when the enaminones were
treated with aniline and 2-amino pyridine. The attempts to
convert 8a–c, 9a–c into their corresponding pyrazole, isox-
azole, pyrimidine, 2-methylpyridine-3-carboxylate failed,
whereas the conversion of 3a–c into 4a–c, 5a–c, 6a–c,
7a–c, 8a–c and 9a–c was successful under the microwave
irradiation, which in turn was also compared with conven-
tional method (Table 3). All these newly synthesized com-
pounds were characterized using 1H-NMR, 13C-NMR, 1H,
1H-COSY, HSQC, DEPT-135 and HRMS (ESI) spectral data
and included in the experimental section.
100
Table 2 Scope of the synthesis of 3-acetyl-4-phenyl quinolines with
DMFDMA
Products Reactants Reagent
Conventional
methoda (in
toluene)
Microwave
methodb
(240 W) (no
solvent)
Yield (%)
Yield (%)
3a
3b
3c
2a
2b
2c
DMFDMA 84
DMFDMA 85
DMFDMA 86
89
91
97
aReaction time: 10 h; b reaction time: 8 min
Experimental
Materials and methods
Melting points (mp) reported in this work were recorded in
Elchem microprocessor-based DT apparatus in open cap-
1
illary tubes and are uncorrected. H NMR and 13C NMR
are recorded either in Bruker 400 or 500 MHz NMR spec-
trometer with TMS as an internal reference. The chemical
shift values are reported in parts per million (δ, ppm) from
internal standard TMS. High-resolution mass spectra were
recorded using Bruker MaXis HRMS (ESI-Q-TOF-MS)
Fig. 1 ORTEP of the compound 3b
Scheme 2 Synthesis of
substituted 4-phenylquinoline
derivatives
Y
O
Y
O
Y
O
N
X
e
f
X
X
NH
N
N
H
N
8a-c
N
3a-c
N
9a-c
NH2
N
NH2
S. No
X
H
Y
H
H
Reagents and conditions:
e, f = Reflux in DMF, 6-8 hrs
8a, 9a
8b, 9b Cl
8c, 9c Cl Cl
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Chemical Papers
Table 3 Scope of the reaction
under conventional and
Products
Conventional method
Microwave-assisted method (240 W)
microwave-assisted methods
Solvents
Temp (°C)
Time (h)
Yield (%)
Solvent
Time (mins)
Yield (%)
4a
4b
4c
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
9a
9b
9c
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
DMF
DMF
DMF
AcOH
AcOH
AcOH
DMF
DMF
DMF
DMF
DMF
DMF
80
80
80
80
80
7
7
7
7
7
55
54
51
45
48
46
29
27
28
39
37
38
28
27
21
29
24
25
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
4
4
4
4
4
4
6
6
6
8
8
8
8
8
8
6
6
6
91
92
90
87
88
89
88
89
91
92
93
94
89
90
91
80
91
81
80
7
130
130
130
118
118
118
130
130
130
130
130
130
12
12
12
12
12
12
24
24
24
24
24
24
instrument. Microwave oven used is synthetic microwave:
CATA R with maximum power of 700 W. All reagents were
purchased from Aldrich and used as received. Solvents were
removed under vacuum. Organic extracts were dried with
anhydrous Na2SO4. Silica gel 60F254 aluminium sheets were
used in analytical thin-layer chromatography. Visualization
of spots on TLC plates was afected by UV illumination,
exposure to iodine vapour and heating the plates dipped in
KMnO4 stain. In column chromatography, the silica gel with
230–400 mesh size was used for the purifcation.
1-(2-Methyl-4-phenylquinolin-3-yl)ethanone (2a) Yellow
1
solid, yield 90%, m.p.: 112–113 °C; H NMR (400 MHz,
CDCl3): δ ppm 8.07 (d, J = 8.10 Hz, 1H, H-8), 7.69 (dt,
J = 2.30 Hz, 8.10 Hz, 1H, H-7), 7.61 (d, J = 7.40 Hz, 1H,
H-6), 7.50 (dd, J = 2.30 Hz, 4.80 Hz, 3H, H-5, 12 & 13),
7.41 (d, J = 7.40 Hz, 1H, H-9), 7.35 (dd, J = 2.30 Hz,
4.80 Hz, 2H, H-10 & 11), 2.70 (s, 3H, CH3, H-16), 1.99
(s, 3H, CH3, H-14); 13C NMR (100 MHz, CDCl3): δ ppm
205.30 (C-15), 153.98 (C-2), 145.94 (C-3), 143.14 (C-4),
135.51 (C-17), 134.50 (C-8a), 132.51 (C-8), 131.02 (C-7),
130.55 (C-6), 129.95 (C-5a), 129.25 (C-5), 128.97 (C-9 &
13), 125.90 (C-10 & 12), 124.94 (C-11), 31.85 (C-16), 23.84
(C-14).
General procedure for the synthesis of compounds (2a–c)
0.1 g (0.5 mmol, 1 eq) of 2-amino benzophenone 1a was
treated with 0.2 mL (0.5 mmol, 1 eq) of acetyl acetone in the
presence of 0.04 mL (0.7 mmol, 1.5 eq) of ortho-phosphoric
acid as catalyst in 5 mL of ethanol and refuxed for 12 h.
After the completion of the reaction, the crude was poured
into ice-cold water and the formed precipitate was fltered
and dried to aford the product 2a. The obtained product
was used without further purifcation and the procedure was
repeated with 1b–c to get 2b–c.
1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)ethanone
(2b) Yellow solid, yield 93%, m.p.: 152–153 °C; 1H NMR
(400 MHz, CDCl3): δ ppm 8.01 (d, J = 8.80 Hz, 1H,
H-8), 7.65 (dd, J = 2.40 Hz, 8.80 Hz, 1H, H-7), 7.57 (d,
J = 2.40 Hz, 1H, H-5), 7.53 (t, J = 3.30 Hz, 3H, H-9, 10
& 11), 7.33 (dd, J = 3.30 Hz, 6.60 Hz, 2H, H-12 & 13),
2.68 (s, 3H, CH3, H-16), 2.00 (s, 3H, CH3, H-14); 13C NMR
(100 MHz, CDCl3): δ ppm 205.25 (C-15), 153.98 (C-2),
145.94 (C-3), 143.15 (C-4), 135.53 (C-17), 134.51 (C-8a),
132.52 (C-8), 131.01 (C-7), 130.54 (C-6), 129.25 (C-5a),
129.09 (C-5), 128.95 (C-9 & 13), 128.32 (C-10), 125.91
(C-11), 124.94 (C-12), 31.83 (C-16), 23.80 (C-14).
Y
O
5
4
X
5a
8a
3
6
1-(6-Chloro-4-(2-chlorophenyl)-2-methylquinolin-3-yl)
ethanone (2c). Yellow solid, yield 93%, m.p.: 137–138 °C;
1H NMR (400 MHz, CDCl3): δ ppm 8.02 (d, J = 8.80 Hz,
1H, H-8), 7.65 (dd, J = 8.80 Hz, 2.40 Hz, 1H, H-7), 7.58
(d, J = 8.00 Hz, 1H, H-5), 7.49 (dt, J = 8.00 Hz, 1H, H-10),
7
N
2
8
1
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Chemical Papers
7.42 (t, J = 7.40 Hz, 1H, H-11), 7.28 (d, J = 2.40 Hz, 1H,
H-12), 7.24 (dd, J = 7.40 Hz, 1.40 Hz, 1H, H-13), 2.71
(s, 3H, CH3, H-16), 2.16 (s, 3H, CH3, H-14); 13C NMR
(100 MHz, CDCl3): δ ppm 204.41 (C-15), 154.08 (C-2),
145.56 (C-3), 135.71 (C-17), 133.40 (C-8a), 133.36 (C-8),
132.84 (C-8), 132.04 (C-7), 131.23 (C-6), 130.88 (C-5a),
130.60 (C-5), 130.07 (C-9), 127.43 (C-10), 125.45 (C-11 &
12), 124.60 (C-13), 31.29 (C-16), 23.80 (C-14).
H-5), 7.43–7.34 (m, 5H, H-9 to H-13), 7.27 (s, 1H, H-17),
4.90 (s, 1H, H-16), 2.94 (s, 3H, CH3, H-19), 2.74 (s, 3H,
CH3, H-18), 2.63 (s, 3H, CH3, H-14); 13C NMR (100 MHz,
CDCl3): δ ppm 192.17 (C-15), 166.28 (C-2), 145.63 (C-3),
143.21 (C-4), 135.50 (C-20), 131.82 (C-8a), 130.34 (C-5a),
130.18 (C-8), 129.95 (C-7), 128.30 (C-5), 126.46 (C-6),
125.10 (C-9 to C-13), 100.49 (C-17), 60.38 (C-16), 44.92
(C-19), 37.03 (C-18), 23.83 (C-14). HRMS-ESI (m/z) calcd
for C21H19ClN2O [M+H]+ = 351.1264, found = 351.1264.
(E)-1-(6-Chloro-4-(2-chlorophenyl)-2-methylquinolin-
3-yl)-3-(dimethylamino)prop-2-en-1-one (3c) Yellow solid,
yield 97%, m.p.: 187–188 °C; 1H NMR (400 MHz, CDCl3):
δ ppm 8.01 (d, J = 8.60 Hz, 1H, H-8), 7.61 (d, J = 8.60 Hz,
1H, H-7), 7.46 (d, J = 6.80 Hz, 1H, H-10), 7.39–7.36 (m,
1H, H-11), 7.27–7.25 (m, 2H, H-5 & 12), 7.17–7.16 (m, 1H,
H-13), 6.89 (s, 1H, H-17), 5.08 (d, J = 12.80 Hz, 1H, H-16),
2.91 (s, 3H, CH3, H-19), 2.75 (s, 3H, CH3, H-18), 2.69 (s,
3H, CH3, H-14); 13C NMR (100 MHz, CDCl3): δ ppm
192.45 (C-15), 157.17 (C-2), 156.56 (C-8a), 153.09 (C-5a),
145.29 (C-4), 140.67 (C-20), 134.15 (C-8), 132.49 (C-9),
132.17 (C-17), 131.23 (C-7), 130.48 (C-10), 130.36 (C-11),
130.08 (C-2), 129.22 (C-3), 127.30 (C-6), 125.79 (C-13),
124.72 (C-5), 100.72 (C-16), 44.08 (C-19), 37.04 (C-18),
23.70 (C-14). HRMS-ESI (m/z) calcd for C21H18Cl2N2O
[M+H]+ = 385.0874, found = 385.0875.
General procedure for the synthesis of compounds
(3a–c)
Conventional method
A mixture of 0.1 g (0.5 mmol, 1 eq) of compound 2a and
0.1 mL (0.5 mmol, 1 eq) of DMFDMA in toluene (5 mL)
was refuxed for 10 h to aford the product 3a. The reac-
tion mixture was then evaporated under reduced pressure
to aford the solid, washed with hexane and then dried. The
similar procedure was repeated with 2b–c to get 3b–c. The
obtained product was used for further analysis without any
purifcation process.
Microwave‑assisted synthesis
A mixture of 0.1 g (0.5 mmol, 1 eq) of compound 2a and
0.1 mL (0.5 mmol, 1 eq) of DMFDMA was mixed together
in a tightly closed tube, and then subjected to microwave
irradiation (240 W) for 8 min (The completion of the reac-
tion was monitored by TLC). The obtained solid formed
was collected and purifed by recrystallization using ethanol
to aford product 3a. Similar procedure was repeated with
2b–c to get 3b–c.
General procedure for the synthesis of compounds
(4a–c)
Conventional method
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a,
0.05 mL (0.3 mmol, 1 eq) of hydrazine hydrate and acetic
acid (1–2 drops) as catalyst in ethanol (10 mL) was refuxed
at 80 °C for 7 h. The mixture was then extracted with
ethyl acetate, dried over sodium sulphate and concentrated
under reduced pressure to aford the crude product 4a. The
obtained crude product was purifed by column chromatog-
raphy using ethyl acetate/hexane (4:6) eluent. To check the
reproducibility of the reaction and to get 4b–c, the procedure
was repeated with 3b–c.
(E)-3-(Dimethylamino)-1-(2-methyl-4-phenylquinolin-
3-yl)prop-2-en-1-one (3a) Yellow solid, yield 89%, m.p.:
143–144 °C; 1H NMR (400 MHz, CDCl3): δ ppm 8.00 (d,
J = 8.80 Hz, 1H, H-8), 7.61 (dd, J = 2.40 Hz, 8.80 Hz,
1H, H-7), 7.52 (d, J = 2.40 Hz, 2H, H-6&5), 7.44–7.41 (m,
4H, H-9 to 12), 7.36–7.33 (m, 2H, H-13&17), 4.90 (s, 1H,
H-16), 2.94 (s, 3H, CH3, H-19), 2.74 (s, 3H, CH3, H-18),
2.63 (s, 3H, CH3, H-14); 13C NMR (100 MHz, CDCl3): δ
ppm 192.74 (C-15), 162.53 (C-2), 156.28 (C-8a), 155.80
(C-5a), 154.77 (C-4), 147.22 (C-20), 145.60 (C-3), 130.31
(C-8), 130.18 (C-7), 129.95 (C-6), 129.35 (C-5), 128.61
(C-9), 128.30 (C-13), 128.00 (C-10), 126.46 (C-17), 126.33
(C-11), 125.61 (C-12), 99.13 (C-16), 44.88 (C-19), 37.01
(C-18), 23.82 (C-14). HRMS-ESI (m/z) calcd for C21H20N2O
[M + H]+ = 317.1654, found = 317.1657.
Microwave‑assisted synthesis
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a and
0.05 mL (0.3 mmol, 1 eq) of hydrazine hydrate was mixed
together in a tightly closed tube, and subjected to microwave
irradiation for about 4 min (the completion of the reaction
was monitored by TLC). The obtained crude product was
purifed by column chromatography using ethyl acetate/hex-
ane (4:6) eluent. To check the reproducibility of the reaction
and to get 4b–c, the procedure was repeated with 3b–c.
(E)-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-
3-(dimethylamino)prop-2-en-1-one (3b). Pale yellow
1
solid, yield 91%, m.p.: 191–192 °C; H NMR (400 MHz,
CDCl3): δ ppm 8.03 (d, J = 8.80 Hz, 1H, H-8), 7.60 (dd,
J = 1.65 Hz, 8.80 Hz, 1H, H-7), 7.52 (d, J = 1.65 Hz, 1H,
1 3

Chemical Papers
2-Methyl-4-phenyl-3-(1H-pyrazol-3-yl)quinolone (4a).
Light yellow solid, yield 91%, m.p.: 214–216 °C; 1H NMR
(400 MHz, CDCl3): δ ppm 8.00 (d, J = 10.20 Hz, 1H,
H-8), 7.61 (dd, J = 2.00 Hz, 10.20 Hz, 1H, H-7), 7.44 (dd,
J = 2.00 Hz, 10.20 Hz, 2H, H-6 & 5), 7.32 (t, J = 2.60 Hz,
4H, H-9 to 12), 7.13 (dd, J = 2.60 Hz, 6.00 Hz, 2H, H-13
& 17), 6.01 (d, J = 2.00 Hz, 1H, H-15), 2.95 (s, 3H, CH3,
H-14), 1.25 (s, 1H, –NH); 13C NMR (100 MHz, CDCl3): δ
ppm 158.82 (C-2), 147.69 (C-8a), 145.78 (C-5a), 135.93
(C-4), 131.84 (C-3), 130.54 (C-8), 130.51 (C-16), 130.34
(C-20), 129.63 (C-7), 128.07 (C-17), 127.94 (C-10, 11
& 12), 126.75 (C-6 & 5), 125.36 (C-10 & C-13), 107.33
(C-15), 24.91 (C-14). HRMS-ESI (m/z) calcd for C19H15N3
[M+H]+ = 286.0944, found = 286.0915.
ice water; the obtained crude was fltered and dried to aford
the product 5a. The obtained product was purifed by col-
umn chromatography using ethyl acetate/hexane (4:6) elu-
ent. Similar procedure was adopted with 3b–c to get 5b–c.
Microwave‑assisted synthesis
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a and
0.02 g (0.3 mmol, 1 eq) of hydroxylamine hydrochloride
was mixed together in a tightly closed tube, and subjected to
microwave irradiation (240 W) for 4 min (the completion of
the reaction was monitored by TLC). The obtained product
was purifed by column chromatography using ethyl acetate/
hexane (4:6) eluent. Similar procedure was adopted with
3b–c to get 5b–c.
6-Chloro-2-methyl-4-phenyl-3-(1H-pyrazol-3-yl)qui-
nolone (4b) Yellow solid, yield 92%, m.p.: 217–218 °C;
1H NMR (400 MHz, CDCl3): δ ppm 8.02 (d, J = 8.90 Hz,
1H, H-8), 7.62 (dd, J = 2.30 Hz, 8.90 Hz, 1H, H-7),
7.46 (d, J = 2.30 Hz, 1H, H-9), 7.43 (s, 1H, H-5), 7.33
(t, J = 2.90 Hz, 3H, H-10 to 12), 7.14 (dd, J = 2.90 Hz,
6.20 Hz, 2H, H-13 & 16), 6.02 (s, 1H, H-15), 2.61 (s, 3H,
CH3, H-14), 1.25 (s, 1H, –NH); 13C NMR (100 MHz,
CDCl3): δ ppm 158.86 (C-2), 147.68 (C-8a), 145.82 (C-5a),
135.96 (C-4), 135.80 (C-3), 131.85 (C-20) 131.84 (C-17),
130.53 (C-8), 130.30 (C-16), 129.66 (C-7), 128.11 (C-9 &
13), 127.97 (C-10, 11 & 12), 126.80 (C-6), 126.79 (C-5),
125.38 (C-15), 24.96 (C-14). HRMS- ESI (m/z) calcd for
C19H14ClN3 [M+H]+ = 320.0955, found = 320.0951.
6-Chloro-4-(2-chlorophenyl)-2-methyl-3-(1H-pyra-
zol-3-yl)quinolone (4c). Yellow solid, yield 90%, m.p.:
219–220 °C; 1H NMR (500 MHz, CDCl3): δ ppm 8.08 (d,
J = 9.00 Hz, 1H, H-8), 7.66 (dd, J = 1.25 Hz, 9.00 Hz,
1H, H-7), 7.46 (d, J = 6.85 Hz, 2H, H-5 & 13), 7.32 (t,
J = 6.85 Hz, 1H, H-10), 7.24 (t, J = 1.25 Hz, 2H, H-11&
12), 7.09 (d, J = 9.00 Hz, 1H, H-16), 6.15 (s, 1H, H-15), 2.66
(s, 3H, CH3, H-14), 1.27 (s, 1H, –NH); 13C NMR (125 MHz,
CDCl3): δ ppm 159.00 (C-2), 145.47 (C-8a), 145.27 (C-5a),
135.14 (C-4), 133.32 (C-17), 132.32 (C-9), 132.20 (C-3),
131.22 (C-16), 130.80 (C-3), 130.35 (C-8), 129.74 (C-7),
129.42 (C-6), 126.64 (C-5), 126.31 (C-10 & 11), 124.74
(C-12 & 13), 106.64 (C-15), 24.72 (C-14). HRMS-
ESI (m/z) calcd for C19H13Cl2N3 [M+H]+ = 354.0565,
found = 354.0554.
3-(Isoxazol-3-yl)-2-methyl-4-phenylquinoline (5a) Yellow
1
solid, yield 87%, m.p.: 159–161 °C; H NMR (400 MHz,
CDCl3): δ ppm 8.05 (d, J = 9.00 Hz, 1H, H-16), 7.69 (dd,
J = 2.25 Hz, 9.00 Hz, 1H, H-8), 7.51 (d, J = 2.25 Hz, 1H,
H-7), 7.40 (dd, J = 2.10 Hz, 5.60 Hz, 1H, H-6), 7.26-7.18
(m, 3H, H-5, 9 & 10), 7.17 (dd, J = 2.10 Hz, 5.60 Hz, 3H,
H-11 to 13), 5.85 (d, J = 2.10 Hz, 1H, H-15), 2.64 (s, 3H,
CH3, H-14); 13C NMR (100 MHz, CDCl3): δ ppm 158.86
(C-2), 147.68 (C-8a), 145.82 (C-5a), 135.96 (C-4), 135.80
(C-3), 131.85 (C-20) 131.84 (C-17), 130.53 (C-8), 130.30
(C-16), 129.66 (C-7), 128.11 (C-9 & 13), 127.97 (C-10,
11 & 12), 126.80 (C-6), 126.79 (C-5), 125.38 (C-15),
24.96 (C-14). HRMS- ESI (m/z) calcd for C19H14N2O
[M+H]+ = 287.1184, found = 287.1185.
6-Chloro-3-(isoxazol-3-yl)-2-methyl-4-phenylquinoline
(5b) Yellow solid, yield 88%, m.p: 156–157 °C; 1H NMR
(400 MHz, CDCl3): δ ppm 8.11 (d, J = 1.20 Hz, 1H, H-16),
8.05 (d, J = 9.10 Hz, 1H, H-8), 7.69 (dd, J = 2.10 Hz,
9.10 Hz, 1H, H-7), 7.51 (d, J = 2.10 Hz, 1H, H-10), 7.40
(t, J = 2.60 Hz, 3H, H-10 to 12), 7.17 (d, J = 2.60 Hz,
2H, H 13 & 16), 5.45 (d, J = 1.20 Hz, 1H, H-15), 2.64
(s, 3H, CH3, H-14); 13C NMR (100 MHz, CDCl3): δ ppm
166.93 (C-17), 157.72 (C-2), 149.99 (C-16), 148.85 (C-8a),
146.56 (C-4), 135.10 (C-20), 132.45 (C-3), 131.83 (C-8),
130.67 (C-7), 129.34 (C-10, 11 & 12), 128.64 (C-9 & 15),
126.27 (C-6), 125.62 (C-5), 121.55 (C-5a), 104.82 (C-15),
24.55 (C-14). HRMS- ESI (m/z) calcd for C19H13ClN2O
[M+H]+ = 321.0795, found = 321.0789.
6-Chloro-4-(2-chlorophenyl)-3-(isoxazol-3-yl)-2-
methylquinoline (5c) Pale yellow solid, yield 89%, m.p.:
General procedure for the synthesis of compounds
(5a–c)
1
151–152 °C; H NMR (400 MHz, CDCl3): δ ppm 8.11
(d, J = 9.10 Hz, 1H, H-16), 8.05 (d, J = 9.10 Hz, 1H,
H-8), 7.69 dd (J = 2.20 Hz, 9.10 Hz, 1H, H-7), 7.51 (d,
J = 2.20 Hz, 1H, H-10), 7.40 (t, J = 2.00 Hz, 2H, H-11
& 12), 7.17 (d, J = 2.20 Hz, 2H, H-13 & 15), 5.85 (d,
J = 2.20 Hz, 1H, H-15), 2.67 (s, 3H, CH3, H-14); 13C NMR
(100 MHz, CDCl3): δ ppm 166.33 (C-17), 157.80 (C-2),
150.02 (C-16), 146.42 (C-4), 145.98 (C-20), 134.23 (C-3),
Conventional method
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a in etha-
nol (10 mL) and 0.02 g (0.3 mmol, 1 eq) of hydroxyl amine
hydrochloride was refuxed at 80 °C for 7 h. After the com-
pletion of the reaction, the reaction mixture was poured into
1 3

Chemical Papers
133.27 (C-8a), 132.82 (C-5a), 131.75 (C-8), 130.87 (C-7),
130.70 (C-9), 130.35 (C-10), 129.63 (C-6), 127.01 (C-11),
125.83 (C-12), 125.02 (C-13), 121.98 (C-5), 104.36 (C-15),
29.69 (C-14). HRMS-ESI (m/z) calcd for C19H12Cl2N2O
[M+H]+ = 355.0405, found = 355.0399.
J = 2.00 Hz, 7.20 Hz, 1H, H-7), 7.49 (d, J = 1.80 Hz, 1H,
H-9), 7.34 (dd, J = 1.80 Hz, 3.80 Hz, 3H, H-10 to 12),
7.17 (dd, J = 2.00 Hz, 3.80 Hz, 2H, H-5 & 13), 6.27 (d,
J = 4.00 Hz, 1H, H-15), 5.10 (s, 2H, –NH), 2.60 (s, 3H, CH3,
H-14); 13C NMR (125 MHz, CDCl3): δ ppm 166.68 (C-2),
162.55 (C-18), 158.17 (C-16), 156.60 (C-17), 145.94 (C-19),
145.73 (C-8a), 135.12 (C-14), 132.08 (C-8), 131.80 (C-3),
130.69 (C-7), 130.44 (C-9, 10 & 11), 129.84 (C-12), 128.21
(C-13 & 5), 126.60 (C-6), 125.32 (C-5a), 113.12 (C-15),
24.52 (C-14). HRMS-ESI (m/z) calcd for C20H15ClN4
[M+] = 346.0985, found = 346.0983.
General procedure for the synthesis of compounds
(6a–c)
Conventional method
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a, 0.04 g
(0.6 mmol, 2 eq) of guanidine hydrochloride and 0.12 g
(0.9 mmol, 3 eq) of potassium carbonate in DMF (5 mL)
was refuxed at 130 °C for 12 h. After completion of the
reaction, reaction mixture was cooled to room temperature,
poured onto ice-cold water and the formed precipitate was
fltered and dried with sodium sulphate to aford the prod-
uct 6a. The obtained crude product was purifed by column
chromatography using ethyl acetate/hexane (4:6) eluent. To
check the reproducibility the compounds 6b–c were derived
from 3b–c by adopting similar procedure.
4-(6-Chloro-4-(2-chlorophenyl)-2-methylquinolin-3-yl)
pyrimidin-2-amine (6c) Dark brown solid, yield 91%, m.p.:
221–223 °C; 1HNMR (400 MHz, CDCl3): δ ppm 8.12 (d,
J = 5.00 Hz, 1H, H-16), 8.05 (d, J = 9.10 Hz, 1H, H-8), 7.65
(dd, J = 2.00 Hz, 9.10 Hz, 1H, H-7), 7.43 (dd, J = 1.20 Hz,
7.90 Hz, 1H, H-10), 7.31 (dt, J = 1.20 Hz, 7.90 Hz, 1H,
H-11), 7.23 (dd, J = 2.00 Hz, 9.10 Hz, 2H, H-5 & 12), 7.10
(dd, J = 1.20 Hz, 7.90 Hz, 1H, H-13), 6.47 (d, J = 5.00 Hz,
1H, H-15), 5.22 (s, 2H, –NH), 2.63 (s, 3H, CH3, H-14);
13C NMR (100 MHz, CDCl3): δ ppm 166.64 (C-18),
162.57 (C-2), 158.13 (C-16), 156.59 (C-17), 144.78 (C-8a),
144.78 (C-19), 135.07 (C-4), 132.01 (C-8), 131.78 (C-3),
130.72 (C-7), 130.39 (C-10, 11 & 12), 129.30 (C-5 & 13),
128.22 (C-6), 129.32 (C-5a), 125.30 (C-9), 111.85 (C-15),
24.49 (C-14). HRMS-ESI (m/z) calcd for C20H14Cl2N4
[M+H]+ = 381.0674, found = 381.0675.
Microwave‑assisted synthesis
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a, guani-
dine hydrochloride (0.6 mmol, 2 eq) and 0.12 g (0.9 mmol,
3 eq) of potassium carbonate in a tightly closed tube was
subjected to microwave irradiation for about 6 min (the com-
pletion of the reaction was monitored by TLC). The obtained
crude product was purifed by column chromatography using
ethyl acetate/hexane (4:6) eluent. To check the reproducibil-
ity the compounds 6b–c were derived from 3b–c by adopting
similar procedure.
General procedure for the synthesis of compounds
(7a–c)
Conventional method
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a in
acetic acid (5 mL), 0.08 mL (0.6 mmol, 2 eq) of ethyl ace-
toacetate and 0.04 g (0.6 mmol, 2 eq) of ammonium acetate
was added. The reaction mixture was heated under refux
for 12 h. After the completion of the reaction, mixture was
cooled, poured onto ice water, the residue obtained was fl-
tered and washed with pet ether to aford the product 7a. The
obtained product was further purifed by column chroma-
tography using ethyl acetate/hexane (4:6) eluent. To check
the reproducibility the same reaction procedure was adopted
with 3b–c which aforded 7b–c.
4-(2-Methyl-4-phenylquinolin-3-yl)pyrimidin-2-amine
1
(6a). Colourless solid, yield 88%, m.p.: 251–252 °C; H
NMR (400 MHz, CDCl3): δ ppm 8.08 (d, J = 5.20 Hz,
2H, H-16), 7.71 (t, J = 7.30 Hz, 1H, H-8), 7.54 (d,
J = 7.30 Hz, 1H, H-7), 7.42 (d, J = 7.30 Hz, 1H, H-6),
7.32 (t, J = 4.00 Hz, 3H, H-10 to 12), 7.19 (t, J = 4.00 Hz,
2H, H-9 & 5), 6.29 (d, J = 5.20 Hz, 1H, H-15), 5.11 (s,
2H, –NH), 2.62 (s, 3H, CH3, H-14); 13C NMR (100 MHz,
CDCl3): δ ppm 167.11 (C-2), 158.21 (C-18), 156.12 (C-17),
147.28 (C-8a), 146.46 (C-19), 135.80 (C-16), 131.01
(C-3), 130.70 (C-8), 130.46 (C-7), 129.95 (C-6), 129.84
(C-5), 129.80 (C-9), 128.77 (C-10), 128.24 (C-11), 127.92
(C-12), 126.57 (C-13), 125.77 (C-4), 125.34 (C-5a), 113.11
(C-15), 24.64 (C-14). HRMS-ESI (m/z) calcd for C20H16N4O
[M+H]+ = 313.1453, found = 313.1454.
Microwave‑assisted synthesis
To a solution of 0.1 g (0.3 mmol, 1 eq) of compound 3a and
acetic acid (5 mL) taken in a tightly closed tube, a mixture
of 0.08 mL (0.6 mmol, 2 eq) of ethylacetoacetate and 0.04 g
(0.6 mmol, 2 eq) of ammonium acetate was added and then
subjected to microwave irradiation (240 W) for 8 min (the
completion of the reaction was monitored by TLC). The
4-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)pyrimidin-
2-amine (6b) Colourless solid, yield 89%, m.p.: 246–247 °C:
1H NMR (500 MHz, CDCl3): δ ppm 8.09 (d, J = 4.00 Hz,
1H, H-16), 8.04 (d, J = 7.20 Hz, 1H, H-8), 7.64 (dd,
1 3

Chemical Papers
obtained product was further purifed by column chroma-
tography using ethyl acetate/hexane (4:6) eluent. To check
the reproducibility the same reaction procedure was adopted
with 3b–c which aforded 7b–c.
126.99 (C-10), 126.24 (C-11 & 12), 121.63 (C-16), 61.38
(C-21), 31.31 (C-23), 24.98 (C-14), 14.14 (C-22). HRMS-
ESI (m/z) calcd for C25H20Cl2N2O2 [M+H]+ = 451.0980,
found = 451.0956.
Ethyl-2-methyl-6-(2-methyl-4-phenylquinolin-3-yl)
pyridine-3-carboxylate (7a) Colourless solid, yield 92%,
General procedure for the synthesis of compounds
(8a–c)
1
m.p.: 140–141 °C; H NMR (400 MHz, CDCl3): δ ppm
8.01 (d, J = 8.80 Hz, 1H, H-8), 7.65 (d, J = 8.80 Hz, 1H,
H-7), 7.57 (s, 2H, H-15 & 16), 7.54–7.53 (m, 4H, H-9,
10, 12 & 13), 7.35–7.33 (m, 3H, H-5, 6 & 11), 4.39 (q,
J = 7.20 Hz, 2H, CH2, H-21), 2.68 (s, 3H, CH3, H-14),
2.00 (s, 3H, CH3, H-23), 1.41 (t, J = 7.20 Hz, 3H, CH3,
H-22); 13C NMR (100 MHz, CDCl3): δ ppm 205.33 (C-20),
165.99 (C-2), 162.24 (C-18), 153.98 (C-17), 145.93 (C-19),
143.14 (C-8a), 140.93 (C-16), 135.51 (C-4), 134.59 (C-24),
132.50 (C-3), 131.03 (C-8), 130.54 (C-7, 9 & 13), 129.96
(C-5), 129.25 (C-15), 128.96 (C-6), 125.89 (C-5a), 124.96
(C-10, 11 & 12), 61.43 (C-21), 31.85 (C-23), 24.98, (C-14),
14.29 (C-22). HRMS- ESI (m/z) calcd for C25H22N2O2
[M+H]+ = 383.1760, found = 383.1733.
Conventional method
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a and
0.03 mL (0.3 mmol, 1 eq) of aniline in DMF (5 mL) was
refluxed at 130 °C for 24 h. The reaction progress was
monitored by TLC. After the completion of the reaction the
solvent was removed under reduced pressure to aford the
product 8a. The obtained product was purifed by column
chromatography with pet ether–ethyl acetate (4:1 v/v) as
an eluent. By adopting the same procedure with 3b–c the
compounds 8b–c were obtained.
Ethyl-6-(6-chloro-2-methyl-4-phenylquino-
lin-3-yl)-2-methylpyridine-3-carboxylate (7b) Yellow
solid, yield 93%, m.p.: 149–151 °C: 1H NMR (400 MHz,
CDCl3): δ ppm 8.02 (d, J = 8.60 Hz, 1H, H-8), 7.65 (dd,
J = 2.20 Hz, 8.60 Hz, 2H, H-7 & 13), 7.58 (d, J = 8.60 Hz,
1H, H-9), 7.49 (dt, J = 1.80 Hz, 7.40 Hz, 2H, H-10 & 11),
7.42 (dt, J = 1.80 Hz, 7.40 Hz, 2H, H-12 & 15), 7.23 (dd,
J = 1.80 Hz, 7.40 Hz, 2H, C-16 & 15), 4.39 (q, J = 7.00 Hz,
2H, CH2, H-21), 2.70 (s, 3H, CH3, H-14), 2.15 (s, 3H, CH3,
H-23), 1.41 (t, J = 7.00 Hz, 3H, CH3, H-22); 13C NMR
(100 MHz, CDCl3): δ ppm 13C NMR (100 MHz, CDCl3):
δ ppm 205.25 (C-20), 153.98 (C-2), 145.95 (C-18), 143.13
(C-17), 140.90 (C-19), 135.53 (C-8a), 132.51 (C-16), 132.50
(C-3), 131.01 (C-4), 130.56 (C-24), 129.95 (C-8), 129.24
(C-7), 128.95 (C-6), 128.14 (C-5, 9 & 13), 125.91 (C-10,
11, 12 & 16), 124.94 (C-15), 61.41 (C-21), 31.83 (C-23),
29.70 (C-14), 23.83 (C-22). HRMS- ESI (m/z) calcd for
C25H21ClN2O2 [M+H]+ = 417.1370, found = 417.1365.
Ethyl-6-(6-chloro-4-(2-chlorophenyl)-2-methylquinolin-
3-yl)-2-methylpyridine-3-carboxylate (7c) Light yellow
Microwave‑assisted synthesis
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a and
0.03 mL (0.3 mmol, 1 eq) of aniline was taken in a tightly
closed tube, and subjected to microwave irradiation for 8 min
(the completion of the reaction was monitored by TLC). The
obtained product was purifed by column chromatography
with pet ether–ethyl acetate (4:1 v/v) as an eluent. By adopt-
ing the same procedure with 3b–c the compounds 8b–c were
obtained.
(E)-1-(2-Methyl-4-phenylquinolin-3-yl)-3-(phenylamino)
prop-2-en-1-one (8a). Brown solid, yield 89%, m.p.:
159–160 °C; 1H NMR (400 MHz, CDCl3): δ ppm 11.72 (d,
J = 12.40 Hz, 1H, –NH), 8.01 (d, J = 8.80 Hz, 1H, H-8), 7.62
(dd, J = 2.40 Hz, 8.80 Hz, 1H, H-7), 7.55 (d, J = 2.40 Hz,
1H, H-6), 7.44 (d, J = 6.80 Hz, 3H, H-5, 9 & 13), 7.35 (d,
J = 7.60 Hz, 3H, H-18 to 20), 7.31 (d, J = 8.00 Hz, 2H, H-21
& 22), 7.16 (dd, J = 7.60 Hz, 12.40 Hz, 1H, H-17), 7.08
(t, J = 7.60 Hz, 1H, H-11), 7.03 (d, J = 8.00 Hz, 2H, H-10
& 12), 5.06 (d, J = 7.60 Hz, 1H, H-16), 2.76 (s, 3H, CH3,
H-14); 13C NMR (100 MHz, CDCl3): δ ppm 194.89 (C-15),
155.79 (C-2), 145.74 (C-8a), 144.16 (C-17), 144.39 (C-23),
139.77 (C-4), 135.41 (C-24), 130.48 (C-8), 130.37 (C-7),
129.89 (C-6), 129.74 (C-5), 128.49 (C-3), 128.39, (C-9 &
13), 126.42 (C-5a), 125.19 (C-10, 11 & 12), 124.08 (C-19,
20 & 21), 116.43 (C-18 & 22), 99.53 (C-16), 24.00 (C-14).
HRMS-ESI (m/z) calcd for C25H20N2O [M+H]+ = 365.1654,
found = 365.1654.
1
solid, yield 94%, m.p.: 143-145 °C: H NMR (400 MHz,
CDCl3): δ ppm 8.02 (d, J = 8.90 Hz, 1H, H-8), 7.65 (dd,
J = 1.30 Hz, 8.90 Hz, 2H, H-7 & 13), 7.58 (d, J = 7.90 Hz,
1H, H-10), 7.49 (dt, J = 1.00 Hz, 7.90 Hz, 1H, H-11),
7.42 (dt, J = 1.00 Hz, 7.90 Hz, 2H, H-12 & 13), 7.23 (dd,
J = 1.30 Hz, 8.90 Hz, 2H, H-16 & 15), 4.40 (q, J = 6.80 Hz,
2H, CH2, H-21), 2.70 (s, 3H, CH3, H-14), 2.15 (s, 3H, CH3,
H-23), 1.42 (t, J = 7.20 Hz, 3H, CH3, H-22); 13C NMR
(100 MHz, CDCl3): δ ppm 204.48 (C-20), 166.39 (C-2),
162.24 (C-18), 154.08 (C-17), 145.65 (C-19), 143.37 (C-8a),
140.94 (C-16), 138.59 (C-24), 135.69 (C-4), 132.80 (C-3),
131.67 (C-8), 131.20 (C-3), 130.88 (C-7), 130.72 (C-9),
130.64 (C-13), 129.84 (C-5), 128.12 (C-15), 127.43 (C-5a),
(E)-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-
(phenylamino)prop-2-en-1-one (8b). Brown solid, yield
1
90%, m.p.: 163–165 °C: H NMR (400 MHz, CDCl3): δ
ppm 11.71 (d, J = 12.40 Hz, 1H, –NH), 8.01 (d, J = 9.00 Hz,
1H, H-8), 7.62 (dd, J = 2.10 Hz, 9.00 Hz, 1H, H-7), 7.54 (d,
1 3

Chemical Papers
J = 2.10 Hz, 1H, H-13), 7.44 (t, J = 6.80 Hz, 3H, H-9 to 11),
7.35 (dd, J = 2.00 Hz, 7.40 Hz, 2H, H-18 to 20), 7.31 (d,
J = 7.80 Hz, 2H, H-21 & 22), 7.16 (dd, J = 7.40, 12.40 Hz,
1H, H-17), 7.09 (d, J = 7.80 Hz, 1H, H-12), 7.02 (d,
J = 8.00 Hz, 2H, H-13 & 5), 5.06 (d, J = 7.40 Hz, 1H, H-16),
2.78 (s, 3H, CH3, H-14); 13C NMR (100 MHz,CDCl3): δ
ppm 194.89 (C-15), 155.75 (C-2), 144.75 (C-8a), 144.15
(C-17), 143.41 (C-23), 139.90 (C-4), 135.43 (C-24), 130.46
(C-8), 130.40 (C-7), 129.90 (C-6), 129.74 (C-5), 128.49
(C-3), 128.38 (C-9 & 13), 126.44 (C-5a), 125.18 (C-10,
11 & 12), 124.08 (C-19, 20 & 21), 116.45 (C-18 & 22),
99.55 (C-16), 23.98 (C-14). HRMS-ESI (m/z) calcd for
C25H19ClN2O [M+H]+ = 399.1264, found = 399.1263.
(E)-1-(6-Chloro-4-(2-chlorophenyl)-2-methylquinolin-
3-yl)-3-(phenylamino)prop-2-en-1-one (8c) Yellow
or 2 drops) as catalyst and a pinch of PTSA was taken in a
tightly closed tube, and subjected to microwave irradiation
for 6 min (the completion of the reaction was monitored by
TLC). The obtained crude product was purifed by column
chromatography using ethyl acetate/hexane (4:6) eluent. To
check the reproducibility of the reaction, 3b–c was subjected
to the same reaction which aforded 9b–c.
(E)-1-(2-Methyl-4-phenylquinolin-3-yl)-3-(pyridin-2-
ylamino)prop-2-en-1-one (9a). Pale yellow solid, yield
1
80%, m.p.: 151–152 °C: H NMR (400 MHz, CDCl3): δ
ppm 11.72 (d, J = 12.30 Hz, 1H), 8.01 (d, J = 8.80 Hz, 1H,
H-19), 7.63 (dd, J = 2.40 Hz, 8.80 Hz, 1H, H-8), 7.55 (d,
J = 2.40 Hz, 1H, H-17), 7.45 (d, J = 6.80 Hz, 3H, H-10
to 12), 7.35 (d, J = 7.60 Hz, 2H, H-13 & 5), 7.32 (d,
J = 8.00 Hz, 2H, H-7), 7.17 (dd, J = 7.60 Hz, 12.40 Hz, 1H,
H-16), 7.08 (t, J = 7.60 Hz, 1H, H-20), 7.03 (d, J = 8.00 Hz,
2H, H-21 & 22), 5.07 (d, J = 7.60 Hz, 1H, H-22), 2.76 (s,
3H, H-14); 13C NMR (100 MHz, CDCl3): δ ppm 194.89
(C-15), 155.75 (C-2), 151.34 (C-23), 148.50 (C-19), 145.74
(C-8a), 144.16 (C-24), 144.39 (C-17), 139.77 (C-24), 135.41
(C-4), 135.25 (C-3), 131.98 (C-8), 130.40 (C-7), 129.89
(C-6), 129.74 (C-5, 9 & 13), 128.49 (C-10, 11 & 12),
126.42 (C-22), 125.19 (C-20 & 22), 124.08 (C-21), 116.43
(C-16), 24.00 (C-14). HRMS-ESI (m/z) calcd for C24H19N3O
[M+H]+ = 366.1606, found = 366.1604.
1
solid, yield 91%, m.p.: 161–162 °C; H NMR (400 MHz,
CDCl3): δ ppm 11.74 (d, J = 12.00 Hz, 1H, –NH), 8.03
(d, J = 9.50 Hz, 1H, H-8), 7.64 (dd, J = 2.60 Hz, 9.50 Hz,
1H, H-7), 7.52 (dd, J = 1.40 Hz, 8.00 Hz, 1H, H-13), 7.41
(dt, J = 1.60 Hz, 7.60 Hz, 1H, H-11), 7.36–7.33 (m, 3H,
H-10, 12 & 14), 7.29 (d, J = 1.40 Hz, 2H, 18 & 19), 7.26
(d, J = 2.60 Hz, 1H, H-22), 7.24–7.21 (m, 1H, H-21 & 22),
7.10 (t, J = 7.60 Hz, 1H, H-17), 7.04 (d, J = 12.00 Hz,
1H, H-11), 5.29 (d, J = 4.00 Hz, 1H, H-16), 2.76 (s, 3H,
CH3, H-14); 13C NMR (100 MHz, CDCl3): δ ppm 194.05
(C-15), 155.99 (C-2), 145.46 (C-8a), 144.57 (C-17), 140.76
(C-23), 139.69 (C-4), 135.52 (C-24), 134.32 (C-9), 133.53
(C-13), 130.63 (C-8), 130.50 (C-7), 130.16 (C-6), 129.75
(C-5), 129.54 (C-3), 127.00 (C-5a), 125.87 (C-10, 11 & 12),
124.73 (C-19, 20 & 21), 116.46 (C-18 & 22), 98.12 (C-16),
23.96 (C-14). HRMS-ESI (m/z) calcd for C25H18Cl2N2O
[M+H]+ = 433.0874, found = 433.0877.
(E)-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-
(pyridin-2-ylamino)prop-2-en-1-one (9b) Yellow solid,
yield 91%, m.p.:169–170 °C: 1H NMR (400 MHz, CDCl3):
δ ppm 11.72 (d, J = 11.90 Hz, 1H), 8.26 (dd, J = 1.80 Hz,
4.90 Hz, 1H, H-19), 8.02 (d, J = 8.80 Hz, 1H, H-8), 7.90 (dd,
J = 7.90 Hz, 11.90 Hz, 1H, H-17), 7.64–7.59 (m, 2H, H-7 &
16), 7.54 (d, J = 1.80 Hz, 1H, H-10), 7.46 (d, J = 4.90 Hz,
3H, H-10 to 12), 7.34 (dd, J = 1.80 Hz, 7.60 Hz, 1H, H-13),
6.97–6.94 (m, 1H, H-20), 6.81 (d, J = 7.90 Hz, 1H, H-21),
5.19 (d, J = 7.90 Hz, 1H, H-22), 2.75 (s, 3H, H-14); 13C
NMR (100 MHz, CDCl3): δ ppm 196.15 (C-15), 155.52
(C-2), 151.33 (C-23), 148.51 (C-19), 145.80 (C-8a), 143.52
(C-24), 142.30 (C-17), 138.42 (C-21), 135.38 (C-4), 135.07
(C-3), 132.06 (C-8), 130.57 (C-7), 130.40 (C-5, 10 & 13),
129.87 (C-11 & 12), 128.45 (C-5a), 126.40 (C-6), 125.18
(C-9), 118.90 (C-20), 111.84 (C-22), 100.96 (C-16),
23.97 (C-14). HRMS-ESI (m/z) calcd for C24H18ClN3O
[M+H]+ = 400.1217, found = 400.1213.
General procedure for the synthesis of compounds
(9a–c)
Conventional method
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a,
0.028 g (0.3 mmol, 1 eq) of 2-aminopyridine, acetic acid (1
or 2 drops) as catalyst and a pinch of PTSA in DMF (10 mL)
was refuxed at 130 °C for 24 h. After the completion of the
reaction, the mixture was cooled and then extracted with
ethyl acetate, dried over sodium sulphate to aford the prod-
uct 9a. The obtained crude product was purifed by column
chromatography using ethyl acetate/hexane (4:6) eluent. To
check the reproducibility of the reaction 3b–c was subjected
to the same reaction which aforded 9b–c.
(E)-1-(6-Chloro-4-(2-chlorophenyl)-2-methylquinolin-
3-yl)-3-(pyridin-2-ylamino)prop-2-en-1-one (9c) Brown
1
solid, yield 81%, m.p.: 158–159 °C; H NMR (400 MHz,
CDCl3): δ ppm 11.72 (d, J = 11.70 Hz, 1H, –NH), 8.14 (d,
J = 5.00 Hz, 1H, H-19), 8.02 (d, J = 8.10 Hz, 1H, H-8),
7.96 (dd, J = 7.80, 11.70 Hz, 1H, H-17), 7.61 (dd, J = 8.10,
14.60 Hz, 2H, H-7 & 16), 7.51 (d, J = 7.60 Hz, 1H, H-10),
7.39 (t, J = 7.60 Hz, 1H, H-11), 7.33 (t, J = 7.30 Hz,
1H, H-21), 7.15 (dd, J = 7.30, 19.00 Hz, 2H, H-13 & 5),
6.95 (t, J = 5.00 Hz, 1H, H-20), 6.80 (d, J = 8.00 Hz, 1H,
Microwave‑assisted synthesis
A mixture of 0.1 g (0.3 mmol, 1 eq) of compound 3a,
0.028 g (0.3 mmol, 1 eq) of 2-aminopyridine, acetic acid (1
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Chemical Papers
Bioorg Med Chem 19:2742–2750. https://doi.org/10.1016/j.
bmc.2011.02.036
H-21), 5.39 (d, J = 8.00 Hz, 1H, H-22), 2.77 (s, 3H, CH3,
H-14). 13C NMR (100 MHz, CDCl3): δ ppm 196.15 (C-15),
155.53 (C-2), 151.34 (C-23), 148.50 (C-19), 145.79 (C-8a),
143.51 (C-24), 142.30 (C-17), 138.42 (C-21), 135.38 (C-4),
135.07 (C-3), 132.06 (C-8), 130.57 (C-7), 130.40 (C-5, 10
& 13), 129.87 (C-11 & 12), 128.45 (C-5a), 126.40 (C-6),
125.18 (C-9), 118.92 (C-20), 111.84 (C-22), 100.96 (C-16),
23.98 (C-14). HRMS-ESI (m/z) calcd for C24H17Cl2N3O
[M+] = 433.0749, found = 433.0746.
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The 3-acetyl-4-arylquinoline-based enaminones were suc-
cessfully synthesized by exploring the synthetic potential
of DMFDMA under microwave-assisted solvent-free condi-
tions (along with that the conventional procedure was also
carried out and compared) which in turn were converted
into a series of heterocycles. All the reactions were found to
aford better yield in shorter duration under the microwave-
assisted reaction. Hence, in our opinion, this synthetic proto-
col is a valuable investigation which could make a signifcant
impact on the synthesis of quinoline-based heterocycles.
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Acknowledgements Authors are thankful to the administration, VIT
University, Vellore, India, for providing facilities to carry out the
research work and also thankful to SIF-Chemistry for providing NMR
facility. Authors are thankful to University of Hyderabad Network
Resource Centre (UGC-NRC) for HRMS facility and also NMR facili-
ties. Author L. Jyothish Kumar is thankful to the VIT University for
providing Research Associateship.
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