A One-Pot, Solvent-Free, and Catalyst-Free Synthesis of Substituted (E)-1-Phenyl-3-[2-(piperidin-1-yl)quinolin-3-yl]prop-2-en-1-ones Under Microwave Irradiation

Article abstract of DOI:10.1134/S1070428019110204

A convenient one-pot, three-component, and solvent-free procedure for the preparation of substituted (E)-1-phenyl-3-[2-(piperidin-1-yl)quinolin-3-yl]prop-2-en-1-ones, which has made a significant improvement of previously reported methods, has been develo

Full text of DOI:10.1134/S1070428019110204

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 11, pp. 1772–1776. © Pleiades Publishing, Ltd., 2019.
A One-Pot, Solvent-Free, and Catalyst-Free Synthesis
of Substituted (E)-1-Phenyl-3-[2-(piperidin-1-yl)quinolin-
3-yl]prop-2-en-1-ones Under Microwave Irradiation
V. K. Pujaria,*, S. Vinnakotab, R. K. Kakarlac,
S. Marojua, and A. Ganeshd
a NewAge life Science Pvt Ltd, IDA Phase-II, Mallapur, Hyderabad, Telangana, India
b Department of Chemistry, ICFAI Foundation for Higher Education, Faculty of Science and Technology,
Donthanapally, Hyderabad, Telangana, India
c Department of Chemistry, CMR institute of Technology, Medchal, Hyderabad, Telangana, India
d Hypersynth Life Science, IDA Phase-II, Mallapur, Hyderabad, Telangana, India
*e-mail: pujarivijaykumar7@gmail.com
Received June 12, 2019; revised August 25, 2019; accepted September 3, 2019
Abstract—A convenient one-pot, three-component, and solvent-free procedure for the preparation of
substituted (E)-1-phenyl-3-[2-(piperidin-1-yl)quinolin-3-yl]prop-2-en-1-ones, which has made a significant
improvement of previously reported methods, has been developed. The reaction of chloro aldehydes, ketones,
and piperidine under microwave irradiation afforded the corresponding piperidine-substituted chalcone
derivatives in high yields in shorter reaction times. All the synthesized compounds were characterized by IR
and 1H and 13C NMR spectroscopy, and mass spectroscopy.
Keywords: catalyst-free one-pot reaction, solvent-free reaction, microwave irradiation, quinoline, piperidine,
chalcones
DOI: 10.1134/S1070428019110204
products and drugs and playing significant role in
INTRODUCTION
medicinal chemistry. Several quinoline derivatives
have been reported to exhibit biological activities, such
as antibacterial [2], antimalarial [3], antiallergic [4],
anti-inflammatory [5] and antitumor [6]. Piperidine
derivatives have displayed a wide range of biological
activities, including antihypertensive [7], antimicrobial
[8], anticonvulsant [9], and anti-inflammatory [10].
Chalcone derivatives showed activity as antiviral and
anti-HIV [11], antimalarial [12], antileishmanial [13],
and anti-tubercular agents [14].
One-pot multicomponent synthesis is a promising
alternative to multistep organic synthesis due to time
and energy saving, simple synthetic procedures, and
high bond-forming efficiency. In view of the
popularity of green chemistry, most organic synthetic
chemists began to look for ways to avoid the use of
highly hazardous organic solvents and focused on
solvent-free protocols, which substantially reduces the
risk of environmental pollution. Recently green
chemistry methods have gained wide recognition as
nonconventional techniques for rapid organic
synthesis.
In view the above-mentioned biological importance
and existing synthetic protocols, our research group is
making considerable effort to designing and
implementing innovative synthetic protocols, adopting
a more ecosustainable approach. As part of our
research we found that solvent-free MWI can promote
reactions pathways highly appreciated in terms of
green chemistry. In continuation of our research
toward green chemistry, here we would like to report a
one-pot synthesis of (E)-1-aryl-3-[2-(piperidin-1-yl)-
Microwave irradiation (MWI) has attracted
increasing interest in organic synthesis, because
MW-assisted reactions are convenient, mild, clean, and
feature higher selectivity and easier workup [1].
The quinoline scaffold and its derivatives represent
a major class of heterocycles widely found in natural
1772

A ONE-POT, SOLVENT-FREE, AND CATALYST-FREE SYNTHESIS
1773
Scheme 1.
O
O
H
N
R
solvent-free
H
R
+
+
H3C
catalyst free,
MWI, 360 w,
2_3 min
N
N
N
Cl
O
4a_4j
2
3a_3j
1
R = H (a), 4-Me (b), 4-Meo (c), 4-Cl (d), 4-Br (e), 4-NO2 (f), 2-napthyl (g), 1-napthyl (h), 4-OH (i), 4-F (j).
quinolin-3-yl]prop-2-en-1-one derivatives under MWI
in solvent-free conditions.
heating and stirring. However, it did not give a better
yield even after 12 h. In our effort to increase the yield
further, we carried out the reaction under MWI without
any solvent and catalyst. Surprisingly, this led to a
remarkable improvement in the yield. Next, to evaluate
the effect of microwave frequency on this reaction, we
performed a series of experiments by varying the MW
power (100, 180, 360, and 480 W). As expected, the
highest yield within the shortest reaction time was
obtained in the reaction performed at the MW power
of 360 W (Scheme 1, Table 1).
RESULTS AND DISCUSSION
Initially, a model one-pot three component reaction
carried out by using 2-chloroquinoline-3-carbaldehyde
(1), piperidine (2) and acetophenone (3a) in different
solvents like MeOH, EtOH, DCM, MeCN, and DMF
at room temperature with stirring. However, the
reaction did not give satisfactory yields. When the
reaction was carried out in solvent-free conditions at
room temperature, the yield of the product was below
60% even after 12-h stirring. To overcome this
problem, we further performed the reaction with
Under the optimized reaction conditions, we
synthesized a series of (E)-1-aryl-3-[2-(piperidin-1-yl)-
quinolin-3-yl]prop-2-en-1-ones 4a–4j in yields higher
Table 1. Optimization of the reaction conditions for the synthesis of compound 4a
O
H
N
O
H
catalyst free
H3C
+
+
N
N
N
Cl
O
1
2
3a
4a
Entry no.
Reaction conditions
Reaction time
Isolated yield, %
1
2
MeOH, rt
12 h
12 h
78
83
80
92
75
52
68
72
92
84
EtOH, rt
12 h
12 h
12 h
12 h
3
DCM, rt
4
AcCN, rt
5
DMF,rt
6
Neat, rt
7
MWI, neat, 100 W
MWI, neat, 180 W
MWI, neat, 360 W
MWI, neat, 480 W
8 min
8 min
5 min
5 min
8
9
10
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PUJARI et al.
1774
than 90% (reaction time 5–6 min). All known
compounds 4a–4j were characterized by a comparison
of their melting points and spectral characteristics (IR,
1H and 13C NMR, and mass spectra) with those
reported in the literature (see Experimental). Com-
pounds 4i and 4j were characterized, along with
spectral methods, by elemental analysis.
ethanone (3b). Yield 96%. mp 102–104°C (102°C
[15]). IR spectrum (KBr), ν, cm–1: 2933 (C–H), 1654
(C=O), 1585 (C=C). 1H NMR spectrum, δ, ppm: 8.25 s
(1Harom), 7.98–8.02 m (3Harom), 7.82 d (1Harom), 7.67–
7.73 m (2Harom), 7.59 t (1Harom), 7.32–7.37 m (3Harom),
3.34 t (4H, 2N–CH2), 2.45 s (3H, CH3), 1.77 m (4H,
2N–CH2–CH2), 1.66 t (2H, CH2). 13C NMR spectrum,
δ, ppm: 189.9, 160.7, 147.8, 143.7, 142.1, 136.8,
135.4, 130.3, 129.4, 128.7, 127.7, 127.4, 124.7, 124.2,
123.2, 122.6, 51.8, 26.0, 24.6, 21.7. Mass spectrum:
m/z 357 [M + H]+.
EXPERIMENTAL
The melting points were determined in open
capillary tubes and are uncorrected. The purity of
compounds was checked by TLC on Merck silica gel
60 F254 plates in ethyl acetate and n-hexane solvent
system. The IR spectra in KBr were recorded on a
Shimadzu FT-IR-8400s spectrophotometer. All the
1H and 13C NMR spectrum were recorded in CDCl3
on a Bruker Avance II spectrometer at 400 (1H) and
100 (13C) MHz using TMS as internal standard. The
mass spectra were recorded on a Shimadzu GCMS-QP
1000 EX instrument. Elemental analysis was perfor-
med on a ThermoFinnigan CHNS analyzer.
(E)-1-(4-Methoxyphenyl)-3-[2-(piperidin-1-yl)-
quinolin-3-yl]prop-2-en-1-one (4c) was synthesized
with 1-(4-methoxyphenyl)ethanone 3c. Yield 96%, mp
128–130°C (128°C [15]). IR spectrum, ν, cm–1: 2924
1
(C–H), 1660 (C=O), 1595 (C=C). H NMR spectrum,
δ, ppm: 8.15 d (2Harom), 8.07–8.10 m (3Harom), 7.70 d
(1Harom), 7.63 d (1Harom), 7.53 t (1Harom), 7.46 d
(1Harom), 7.20 t (1Harom), 6.99 d (2Harom), 3.90 s (3H,
OCH3), 3.69 t (4H, 2N–CH2), 1.92 m (4H, 2N–CH2–
CH2), 1.71 t (2H, CH2). 13C NMR spectrum, δ, ppm:
188.6, 163.5, 160.7, 147.8, 141.7, 136.8, 130.9, 130.8,
130.2, 127.7, 127.4, 124.7, 124.2, 123.3, 122.4, 113.9,
113.8, 55.5, 51.7, 26.0, 24.6. Mass spectrum: m/z 373
[M + H]+.
Synthesis of (E)-1-aryl-3-[2-(piperidin-1-yl)qui-
nolin-3-yl]prop-2-en-1-ones 4a–4j (general procedure).
A quartz tube was charged with mixture of 1 mmol of
2-chloroquinoline-3-carbaldehyde (1), 1 mmol of subs-
tituted acetophenone 3a–3j, and 2 mmol of piperidine
was inserted into a Teflon vial with a screw cap and
subjected to MWI (360 W) for 5–6 min. The reaction
progress was monitored by TLC. After completion of
the reaction, the reaction mixture was poured into ice-
cold water, and the solid material that slowly
precipitated was filtered off, washed with water, dried,
and purified by column chromatography using silica
gel (100–200 mesh) in n-hexane–ethyl acetate (9 : 1)
to obtain a pure product.
(E)-1-(4-Chlorophenyl)-3-[2-(piperidin-1-yl)qui-
nolin-3-yl]prop-2-en-1-one (4d) was synthesized with
1-(4-chlorophenyl)ethanone 3d. Yield 95%. mp 136–
138°C (136°C [15]). IR spectrum, ν, cm–1: 2927 (C–H),
1
1658 (C=O), 1593 (C=C). H NMR spectrum, δ, ppm:
8.24 s (1Harom), 8.00 m (3Harom), 7.82 d (1Harom), 7.71 d
(1Harom), 7.60–7.66 m (2Harom), 7.49 d (2Harom), 7.34 t
(1Harom), 3.34 t (4H, 2N–CH2), 1.77 m (4H, 2N–CH2–
CH2), 1.67 t (2H, CH2). 13C NMR spec-trum, δ, ppm:
189.1, 160.7, 147.9, 143.1, 139.3, 137.0, 136.3, 130.5,
129.9, 129.0, 127.8, 127.5, 124.6, 124.3, 122.9, 121.9,
51.8, 26.0, 24.6. Mass spectrum: m/z 377 [M + H]+.
(E)-1-Phenyl-3-[2-(piperidin-1-yl)quinolin-3-yl]-
prop-2-en-1-one (4a) was synthesized with acetophe-
none 3a. Yield 94%. mp 141–143°C (142°C [15]). IR
spectrum, ν, cm–1: 3059 (C–H), 1654 (C=O), 1593
(E)-1-(4-Bromophenyl)-3-[2-(piperidin-1-yl)qui-
nolin-3-yl]prop-2-en-1-one (4e) was synthesized with
1-(4-bromophenyl)ethanone (3e). Yield 96%. mp 120–
122°C (120°C [15]). IR spectrum, ν, cm–1: 2926 (C–H),
1
(C=C). H NMR spectrum, δ, ppm: 8.25 s (1Harom),
8.06 d (2Harom), 7.98 d (1Harom), 7.82 d (1Harom), 7.52–
7.73 m (7Harom), 7.34 t (1Harom), 3.35 t (4H, 2N–CH2),
1.77 m (4H, 2N–CH2–CH2), 1.66 t (2H, CH2). 13C
NMR spectrum, δ, ppm: 190.2, 160.5, 148.1, 142.9,
142.2, 137.8, 136.7, 132.7, 130.2, 128.5, 128.3, 127.5,
127.2, 124.5, 124.1, 122.5, 122.8, 51.6, 25.8, 24.4.
Mass spectrum: m/z 343 [M + H]+.
1
1658 (C=O), 1591 (C=C). H NMR spectrum, δ, ppm:
8.24 s (1Harom), 8.00 d (1Harom), 7.93 d (2Harom), 7.82 d
(1Harom), 7.71 d (1Harom), 7.60–7.68 m (4Harom), 7.34 t
(1Harom), 3.33 t (4H, 2N–CH2), 1.75 m (4H, 2N–CH2–
CH2), 1.66 t (2H, CH2). 13C NMR spectrum, δ, ppm:
189.3, 160.7, 147.9, 143.2, 137.1, 136.8, 132.0, 130.5,
130.0, 129.9, 128.0, 127.8, 127.5, 124.6, 124.3, 122.9,
121.9, 51.8, 26.0, 24.6. Mass spectrum: m/z 421 [M +
H]+.
(E)-3-[2-(piperidin-1-yl)quinolin-3-yl]-1-(p-tolyl)-
prop-2-en-1-one (4b) was synthesized with 1-(p-tolyl)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

A ONE-POT, SOLVENT-FREE, AND CATALYST-FREE SYNTHESIS
1775
(E)-1-(4-Nitrophenyl)-3-[2-(piperidin-1-yl)quino-
lin-3-yl]prop-2-en-1-one (4f) was synthesized with
1-(4-nitrophenyl)ethanone (3f). Yield 92%. mp 191–
194°C (192°C [5]). IR spectrum, ν, cm–1: 2920 (C–H),
129.7, 126.5, 126.3, 124.1, 122.0, 114.5, 51.8, 26.1,
24.6. Found, %: C 77.02; H 6.13; N 7.86 C23H22N2O2.
Calculated, %: C 77.07; H 6.19; N 7.82. Mass spec-
trum: m/z 359 [M + H]+.
1
1664 (C=O), 1583 (C=C). H NMR spectrum, δ, ppm:
(E)-1-(4-fluorophenyl)-3-[2-(piperidin-1-yl)qui-
nolin-3-yl]prop-2-en-1-one (4j) was synthesized with
1-(4-fluorophenyl)ethanone (3j). Yield 95%, mp 167–
169°C. IR spectrum, ν, cm–1: 2927 (C–H), 1658
(C=O), 1593 (C=C). 1H NMR spectrum, δ, ppm: 8.25 s
(1Harom), 7.98 m (3Harom), 7.81 d (1Harom), 7.72 d
(1Harom), 7.50–7.66 m (4Harom), 7.34 t (1Harom), 3.34 t
(4H, 2N–CH2), 1.77 m (4H, 2N–CH2–CH2), 1.66 t
(2H, CH2). 13C NMR spectrum, δ, ppm: 189.2, 163.5,
160.7, 147.8, 143.2, 139.3, 136.3, 130.1, 129.0, 127.5,
127.2, 124.5, 124.1, 122.3, 119.9, 51.8, 26.0, 24.6.
Found, %: C 76.68; H 5.91; N 7.72 C23H21FN2O. Cal-
culated, %: C 76.64; H 5.87; N 7.77. Mass spectrum:
m/z 361 [M + H]+.
8.20–8.38 m (4Harom), 8.04–8.07 m (1Harom), 7.63–7.84 m
(4Harom), 7.30 d (2Harom), 3.34 t (4H, 2N–CH2), 1.76 m
(4H, 2N–CH2–CH2), 1.67 t ( 2H, CH2). 13C NMR
spectrum, δ, ppm: 189.0, 160.7, 150.1, 148.1, 144.6,
142.9, 137.4, 130.8, 129.4, 127.9, 127.5, 124.6, 124.5,
123.9, 122.4, 121.6, 51.9, 26.0, 24.5. Mass spectrum:
m/z 388 [M + H]+.
(E)-1-(Naphthalen-2-yl)-3-[2-(piperidin-1-yl)qui-
nolin-3-yl]prop-2-en-1-one (4g) was synthesized with
1-(naphthalen-2-yl)ethanone (3g). Yield 95%, mp
185–187°C (186°C [15]). IR spectrum, ν, cm–1: 2927
1
(C–H), 1654 (C=O), 1583 (C=C). H NMR spectrum,
δ, ppm: 8.61 s (1Harom), 8.31 s (1Harom), 8.14–8.17 m
(1Harom), 8.06 d (1Harom), 8.02 d (1Harom), 7.96 d
(1Harom), 7.84–7.93 m (3Harom), 7.75 d (1Harom), 7.57–
7.65 m (3Harom), 7.35 t (1Harom), 3.36 t (4H, 2N–CH2),
1.78 m (4H, 2N–CH2–CH2), 1.66 t (2H, CH2). 13C
NMR spectrum, δ, ppm: 190.1, 160.8, 147.9, 142.5,
137.0, 135.5, 135.4, 132.6, 130.4, 130.0, 129.5, 128.6,
128.4, 127.9, 127.8, 127.4, 126.8, 124.7, 124.5, 124.3,
123.2, 122.5, 51.8, 26.0, 24.6. Mass spectrum: m/z 393
[M + H]+.
CONCLUSIONS
A high-yield one-pot, multicomponent, MW-
assisted, and catalyst- and solvent-free protocol for the
synthesis of (E)-1-aryl-3-[2-(piperidin-1-yl)quinolin-3-
yl]prop-2-en-1-ones was successfully developed. The
method proved to be simple and easy-to-perform, and
provides high yields within a short time.
(E)-1-(Naphthalen-1-yl)-3-[2-(piperidin-1-yl)qui-
nolin-3-yl]prop-2-en-1-one (4h) was synthesized with
1-(naphthalen-1-yl)ethanone (3h). Yield 94%, mp
132–134°C (132°C [15]). IR spectrum, ν, cm–1: 2932
SUPPLEMENTARY MATERIALS
Supplementary materials are available for this
article at https://doi.org/10.1134/S1070428019110204
and are accessible for authorized users.
1
(C–H), 1657 (C=O), 1582 (C=C). H NMR spectrum,
δ, ppm: 8.25 s (1Harom), 7.87–8.01 m (4Harom), 7.56–
7.81 m (7Harom), 7.35–7.41 m (2Harom), 3.23 t (4H, 2N–
CH2), 1.52–1.60 m (6H, CH2, N–CH2–CH2). 13C NMR
spectrum, δ, ppm: 190.1, 160.7, 146.9, 143.1, 135.5,
131.6, 130.4, 129.2, 128.4, 128.0, 127.9, 127.87,
127.4, 126.8, 124.8, 124.6, 122.2, 120.5, 51.7, 26.0,
24.6. Mass spectrum: m/z 393 [M + H]+.
ACKNOWLEDGMENTS
The authors are grateful to the Department of Chemistry,
CMR Institute of Technology and Department of Chemistry,
ICFAI Foundation for Higher Education, Hyderabad, India
for providing laboratory facilities.
(E)-1-(4-hydroxyphenyl)-3-[2-(piperidin-1-yl)-
quinolin-3-yl]prop-2-en-1-one (4i) was synthesized
with 1-(4-hydroxyphenyl)ethanone (3a). Yield 92%,
mp 171–173°C. IR spectrum, ν, cm–1: 2926 (C–H),
CONFLICT OF INTEREST
The authors declare no conflict of interest.
1
1658 (C=O), 1591 (C=C). H NMR spectrum, δ, ppm:
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(4H, 2N–CH2), 1.76 m (4H, 2N–CH2–CH2), 1.66 t
(2H, CH2). 13C NMR spectrum, δ, ppm: 189.2, 160.6,
153.5, 147.9, 143.2, 137.1, 136.5, 131.7, 131.5, 130.2,
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