Simple and efficient synthesis of 2-aryl-2,3-dihydroquinolin-4(1H)-ones using silica chloride as a new catalyst under solvent-free conditions

Article abstract of DOI:10.1080/00397910903097252

A mild, efficient, and high-yielding method for the synthesis of 2-aryl-2,3-dihydroquinolin-4(1H)-ones from their corresponding 2-amino chalcones using silica chloride (SiO2Cl) under solvent-free conditions is described. A series of 2-aryl-2,3-dihydroquinolin-4(1H)-ones containing both electron-donating and electron-withdrawing substituents were synthesized.

Full text of DOI:10.1080/00397910903097252

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Simple and Efficient Synthesis of 2-
Aryl-2,3-Dihydroquinolin-4(1H)-ones
Using Silica Chloride as a New Catalyst
Under Solvent-Free Conditions
M. Muthukrishnan a , M. Mujahid a , V. Punitharasu a & D. A.
Dnyaneshwar a
a Organic Chemistry Division, National Chemical Laboratory, Pune,
India
Version of record first published: 07 Apr 2010.
To cite this article: M. Muthukrishnan , M. Mujahid , V. Punitharasu & D. A. Dnyaneshwar (2010):
Simple and Efficient Synthesis of 2-Aryl-2,3-Dihydroquinolin-4(1H)-ones Using Silica Chloride as a New
Catalyst Under Solvent-Free Conditions, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:9, 1391-1398
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Synthetic Communications1, 40: 1391–1398, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903097252
SIMPLE AND EFFICIENT SYNTHESIS OF
2-ARYL-2,3-DIHYDROQUINOLIN-4(1H)-ONES USING
SILICA CHLORIDE AS A NEW CATALYST UNDER
SOLVENT-FREE CONDITIONS
M. Muthukrishnan, M. Mujahid, V. Punitharasu, and
D. A. Dnyaneshwar
Organic Chemistry Division, National Chemical Laboratory, Pune, India
A mild, efficient, and high-yielding method for the synthesis of 2-aryl-2,3-dihydroquinolin-
4(1H)-ones from their corresponding 2-amino chalcones using silica chloride (SiO2Cl)
under solvent-free conditions is described. A series of 2-aryl-2,3-dihydroquinolin-4(1H)-ones
containing both electron-donating and electron-withdrawing substituents were synthesized.
Keywords: 2-Amino chalcones; 2-aryl-2,3-dihydroquinolin-4(1H)-ones; microwave; silica chloride
The versatility of flavonoid derivatives for the synthesis of nitrogen-containing
flavonoid mimics of biological importance has been well documented.[1] Substituted
4(1H)-quinolones, in particular 2-aryl-2,3-dihydroquinolin-4(1H)-ones, are important
aza analogs of flavanoid derivatives and possess numerous therapeutic functions.[1,2]
Moreover, these substituted 2,3-dihydro quinolin-4(1H)-ones are valuable precursors
for the synthesis of other medicinally important compounds such as 4-alkoxy-2-
aryl quinolines,[3,5] 2-aryl-4-quinolones (azaflavones),[4] and 3-aryl-4-quinolones
(azaisoflavones).[5]
The methodology most widely used to prepare 2-aryl-2,3-dihydroquino-
lin-4(1H)-ones involves the isomerization of appropriately substituted 2-amino
chalcones, in turn obtained by an aldol condensation reaction between a 2-amino
acetophenone and an aldehyde. These cyclizations have been carried out under
numerous conditions using acids,[6] bases,[7] and others.[8] Very recently, InCl3,[9]
CeCl3 ꢀ 7H2O,[10] and TaBr5 supported on inorganic solid support have also been
[11]
successfully used for such cyclization. However, most of these procedures have lim-
ited synthetic utility because of the use of corrosive acids such as orthophosphoric
acid or formic acid, strong alkalis, hazardous and expensive reagents, or poor yield.
In recent times, solvent-free organic reactions coupled with microwave
exposure of neat reactants catalyzed by the surface of less expensive and recyclable
mineral supports such as silica gel, alumina, or clay have been gaining importance
Received March 19, 2009.
Address correspondence to M. Muthukrishnan, Organic Chemistry Division, National Chemical
Laboratory, Pune 411 008, India. E-mail: m.muthukrishnan@ncl.res.in
1391

1392
M. MUTHUKRISHNAN ET AL.
because of their applicability in wide range of organic transformations, enhanced
reaction rates, greater yields, ease of manipulation, and finally the possibility of
upscaling the reactions to multigram scale.[12]
With this in mind and given our interest in studying the utility of silica chloride
(SiO2Cl) as a new catalyst for useful organic transformations, herein we report a sim-
ple and rapid method for the synthesis of 2-aryl-2,3-dihydroquinolin-4(1H)-ones
through the cyclization of 2-amino chalcones using easily accessible and nonhazar-
dous silica chloride under solvent-free conditions (Scheme 1). To the best of our
knowledge, no previous reports using this catalyst for such cyclization reactions have
been reported.
The experimental procedure is very simple and convenient. In a typical experi-
ment, a thoroughly mixed combination of 2-amino chalcone (1 mmol) and silica
chloride (1:3 ratio; w=w) was irradiated under microwaves in a domestic microwave
oven (600 W) for 3–6 min. The reaction mixture, after being cooled directly charged
on a small silica-gel column and eluted with a mixture of ethylacetate–hexane (1:9),
afforded the corresponding 2-phenyl-2,3-dihydroquinolin-4(1H)-one 2a in 96%
yield.
To explore the scope of the reaction, various substituted 2-amino chalcones
were treated under the reaction conditions to give the corresponding 2-aryl-2,3-
dihydroquinolin-4(1H)-ones in excellent yields. The results are presented in
Table 1. A variety of substituents such as Cl, Me, NO2, OMe, and methylenedioxy
on the aromatic ring B are compatible with this reaction condition.
The possible mechanistic rationale of this reaction is similar to that recently
reported[9] and is depicted in Scheme 2.
We further investigated the possibility of synthesizing 2-aryl-2,3-
dihydroquinolin-4(1H)-ones directly from 2-amino acetophenone, aromatic alde-
hyde, and silica chloride in one pot using the optimized reaction conditions
(Scheme 3). The product formed in poor yield (<30%). However, the efforts made
so far to improve the yields have failed (Table 2).
In conclusion, the present procedure, catalyzed by the simple and easily access-
ible silica chloride, provides an efficient methodology for the synthesis of 2-aryl-2,3-
dihydroquinolin-4(1H)-ones by the microwave-assisted cyclization of 2-amino
chalcones under solvent-free conditions. The significant advantages of this procedure
are (a) very fast reaction time (3–6 min); (b) mild reaction conditions; (c) excellent
yields; and (d) green aspects, including avoiding hazardous reagents, solvents, and
waste. Moreover, this has much promise for further applications of silica chloride
as a catalyst for various organic transformations.
Scheme 1. Cyclization of 2-amino chalcone using silica chloride.

SYNTHESIS OF 2-ARYL-2,3-DIHYDROQUINOLIN-4(1H)-ONES
Table 1. Silica chloride–catalyzed cyclization of 2-amino chalcones
1393
Time
(min)
Yield
(%)a,b
Entry
Substrate
Product
2a
1
3
96
94
96
92
95
2b
2
3
4
5
3
3
3
3
2c
2d
2e
2f
6
7
6
6
90
88
2g
2h
8
5
92
(Continued )

1394
M. MUTHUKRISHNAN ET AL.
Table 1. Continued
Time
(min)
Yield
(%)a,b
Entry
Substrate
Product
2i
9
3
5
90
84
2j
10
2k
11
5
90
2l
12
13
3
6
92
85
2m
2n
14
5
90
2o
15
6
83
(Continued )

SYNTHESIS OF 2-ARYL-2,3-DIHYDROQUINOLIN-4(1H)-ONES
Table 1. Continued
1395
Time
(min)
Yield
(%)a,b
Entry
16
Substrate
Product
2p
2q
6
85
83
17
6
aMicrowave irradiation was carried out at 600 W.
bIsolated and unoptimized yield.
Scheme 2. Plausible mechanism for the silica chloride–catalyzed cyclization of 2-amino chalcone.
Scheme 3. One-pot synthesis of 2-aryl-2,3-dihydroquinolin-4(1H)-ones under silica chloride catalysis.

1396
M. MUTHUKRISHNAN ET AL.
Table 2. Silica chloride–catalyzed, one-pot synthesis of 2-aryl-2,3-dihydroquinolin-4(1H)-ones
Entry
R
Time (min)
Product
Yield (%)a,b
1
2
3
4
H
4-OCH3
2-F
25
25
25
25
2a
2d
2g
2i
28
20
15
15
3,4-(OCH3)2
aMicrowave irradiation was carried out at 600 W.
bIsolated and unoptimized yield.
EXPERIMENTAL
General
Melting points were measured with a Buchi B-540 melting-point apparatus and
are uncorrected. Infrared (IR) spectra (nmax in cmꢁ1) were recorded on a Perkin-
Elmer 283 IR spectrophotometer, and 1H NMR spectra were measured on a Brucker
AC-200 instrument using CDCl3 as solvent and residual solvent as internal standard.
Mass spectra (MS; EI, 70 ev, direct inlet system) was carried out on a Finnigan MAT-
1020 spectrometer. Silica chloride was prepared as per the reported procedure.[13] All
solvents were distilled before use. Thin-layer chromatography (TLC) was performed
on silica-gel-coated glass plates and visualized in ultraviolet (UV) light and=or stained
with iodine.
Typical Experimental Procedure Using 2a as an Example
2-Amino chalcone (0.223 g; 1 mmol) was thoroughly mixed with silica chloride
(0.660 g) in a mortar with a pestle, and the whole mixture was transferred to a 10-mL
tube. The reaction mixture was irradiated in a domestic microwave oven (Samsung,
India) at 600 W for 3 min. On completion, the reaction mixture was directly charged
on a small silica-gel column and eluted with a mixture of ethyl=hexane (1:9) to afford
the pure product 2a (0.214 g) in 96% yield.
Selected Spectroscopic Data for the New Compounds
2-(2-Fluorophenyl)-2,3-dihydroquinolin-4(1H)-one (2g). Pale yellow solid;
=
mp ¼ 126–127 C; IR (CHCl3): 3394 (ꢁNH), 1673 (C O) cmꢁ1: 1H NMR (200 MHz,
ꢂ
CDCl3): d 2.78–2.82 (m, 2 H), 5.05 (dd, 1 H, J ¼ 8.2, 16.5 Hz), 6.65–6.75 (m, 2 H),
6.95–7.30 (m, 4 H), 7.45–7.52 (m, 1 H), 7.78 (dd, 1 H, J ¼ 7.9, 1.6 Hz). 13C NMR
(50 MHz, CDCl3): d ¼ 44.3, 51.0, 116.0, 118.5, 119.0, 124.6, 127.5, 128.0, 129.7,
129.8, 135.5, 151.5, 157.7, 162.6, 193.0; MS (ESI): m=z ¼ 242 [M þ 1]þ, 264
[M þ Na]þ.
2-(2,3-Methylenedioxyphenyl)-2,3-dihydroquinolin-4(1H)-one (2m). Yellow
ꢁ1
;
1H NMR (200 MHz,
=
semisolid; IR (CHCl3): 3397 (ꢁNH), 1671 (C O) cm
CDCl3): d ¼ 2.69–2.92 (m, 2 H), 4.81 (dd, 1 H, J ¼ 4.4, 12.4 Hz), 5.88–5.91 (m, 2
H), 6.62–6.88 (m, 5 H), 7.20–7.29 (m, 1H), 7.77 (dd, 1 H, J ¼ 7.9, 1.5 Hz). 13C
NMR (50 MHz, CDCl3): d ¼ 43.7, 52.5, 101.1, 108.4, 116.0, 118.4, 119.1, 119.4,

SYNTHESIS OF 2-ARYL-2,3-DIHYDROQUINOLIN-4(1H)-ONES
1397
121.8, 122.1, 127.5, 135.4, 144.9, 147.6, 151.3, 193.3; MS (ESI): m=z ¼ 267 [M]þ, 268
[M þ 1]þ.
2-(2-Bromo-4,5-dimethoxyphenyl)-2,3-dihydroquinolin-4(1H)-one (2n)
ꢂ
=
Pale yellow solid; mp ¼ 149–150 C; IR (CHCl3): 3388 (ꢁNH), 1671 (C O)
cmꢁ1; H NMR (200 MHz, CDCl3): d ¼ 2.66–2.93 (m, 2 H), 3.89 (s, 6 H), 5.15
1
(dd, 1H, J ¼ 4.4, 12. Hz), 6.75–6.86 (m, 2 H), 7.03 (s, 1 H), 7.19 (s, 1H), 7.33–7.41
(m, 1 H), 7.89 (dd, 1 H, J ¼ 7.8, 1.4 Hz). 13C NMR (50 MHz, CDCl3): d ¼ 44.5,
56.1, 56.2, 56.7, 109.9, 112.6, 115.4, 116.1, 118.6, 119.0, 127.5, 131.6, 135.3, 148.7,
149.1, 151.5, 192.9. MS (ESI): m=z ¼ 362 [M þ 1]þ, 384 [M þ Na]þ.
2-(2,4-Dimethoxyphenyl)-2,3-dihydroquinolin-4(1H)-one (2o)
1
Yellow semisolid; IR (CHCl3): 3401 (ꢁNH), 1674 (C O) cmꢁ1; H NMR
=
(200 MHz, CDCl3): d ¼ 2.83–2.88 (m, 2 H), 3.79 (s, 6 H), 5.04–5.12 (m, 1 H),
6.52–6.54 (m, 2 H), 6.68–6.79 (m, 2 H), 7.30–7.38 (m, 2 H), 7.84 (dd, 1 H, J ¼ 7.9,
1.3 Hz). 13C NMR (50 MHz, CDCl3): d ¼ 43.8, 51.0, 55.3, 55.4, 98.7, 100.4, 104.2,
106.1, 116.2, 118.1, 121.3, 129.9, 135.2, 157.8, 160.6, 160.8, 194.1. MS (ESI): m=z ¼
306 [M þ Na]þ.
ACKNOWLEDGMENTS
Financial assistance from the Department of Science and Technology, New
Delhi (Project SR=FTP=CS-25=2007) is gratefully acknowledged. The authors thank
Dr. Pradeep Kumar, FNASc, for his constant encouragement and support.
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