Ultrasound promoted one-pot three-component synthesis of novel 7-aryl-8H-benzo[h]indeno[1,2-b]quinolin-8-ones under solvent-free conditions

Article abstract of DOI:10.3184/174751912X13319177859559

A series of novel derivatives of 7-phenyl-8H-benzo[h]indeno[1,2-b]quinolin- 8-ones were synthesised directly by one-pot three-component reaction of indanedione, α-naphthylamine and various substituted arylaldehydes under solvent-free conditions using ultrasonic irradiation as a clean source of energy. This fast method provided the products in high yields (70-93%) and low reaction times (10-75 min).

Full text of DOI:10.3184/174751912X13319177859559

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 235
APRIL, 235–237
Ultrasound promoted one-pot three-component synthesis of novel
7-aryl-8H-benzo[h]indeno[1,2-b]quinolin-8-ones under solvent-free conditions
Manouchehr Mamaghani* and Tahere Hosseyni Larghani
Department of Chemistry, Islamic Azad University, Rasht Branch, Rasht, Iran
A series of novel derivatives of 7-phenyl-8H-benzo[h]indeno[1,2-b]quinolin-8-ones were synthesised directly by
one-pot three-component reaction of indanedione, α-naphthylamine and various substituted arylaldehydes under
solvent-free conditions using ultrasonic irradiation as a clean source of energy. This fast method provided the
products in high yields (70–93%) and low reaction times (10–75 min).
Keywords: 1,3-indanedione, indeno[1,2-b]quinolin-8-ones, quinoline, one-pot synthesis, ultrasound, solvent-free reaction
The quinoline ring is found in a wide variety of biologically
active products which have interesting pharmacological and
biological activities such as anti-malarial, anti-asthmatic,
anti-bacterial and anti-hypersensitive activities.1,2 In par-
ticular, indenoquinoline derivatives have a wide range of
biological activities such as anti-malarial,3 anti-inflammatory,4
anti-tumour,5 and as inhibitor for stereoid reductase.6 There-
fore, several procedures have been reported for their synthesis.
These compounds can be synthesised via a new Friedlander
synthesis from methyl 2-amino-3-formylbenzoate,7 via Pd/C-
assisted dehydrogenation,8 a three-component method through
the Michael addition to enaminones,9 via photoisomerisation
of benzotropolone derivatives,10 microwave-assisted bismuth
nitrate-catalysed synthesis,11 ruthenium-catalysed oxidative
cyclisation of 2-aminobenzyl alcohol with ketones,12 conden-
sation of aminobenzonitrile with indanones in the presence
of ZnCl2,13 or using biradicals/zwitterions from enallene-
isonitriles in a formal [4 + 1] cycloaddition reaction,14 using an
in situ formed Mannich base from α-naphthylamine and indan-
dione in acetic acid15 and employing microwave methodology
in ethylene glycol.16 However, most of the available approaches
for the synthesis of these types of molecules are complex.
Some of these methods involve expensive reagents, stoichio-
metric amounts of catalysts, strongly acidic conditions, longer
reaction times, high temperatures, unsatisfactory yields and
incompatibility with other functional groups. Therefore, the
development of a neutral alternative might extend the scope of
the useful Biginelli reaction.
Ultrasound is widely used for improving traditional reactions
that use expensive reagents, strongly acidic conditions, long
reaction times, high temperatures, and incompatibility with
other functional groups.18 Therefore, prompted by the pro-
nounced effect of ultrasonic irradiation in the rate acceleration
of organic syntheses, it was decided to use this methodology
in the synthesis of novel derivatives of benzo[h]indeno
[1,2-b]quinolin-8-ones.
Results and discussion
In continuation of our efforts to develop practical and
benign methods for the synthesis of heterocycles of biological
importance,19–23 we envisaged that a three-component approach
could be used for the construction of indenoquinoline types of
molecules in a single step. A simple, mild and expeditious
method was developed for the preparation of new derivatives
of benzo[h]indeno[1,2-b]quinolin-8-ones in a one-pot three-
component approach under solvent-free conditions without a
catalyst (Scheme 1). In this protocol, the desired indenoquino-
lines (4a–j) were synthesised by the reaction of equimolar
amounts of indanedione, α-naphthylamine and various aryl
aldehydes in the absence of catalyst and solvent, under ultra-
sonic irradiation (45 kHz) at 60 °C in good to high yields
(73–93%) (Table 1). Our literature search revealed that there
is no previous general study of the compounds described
here. However, compounds 4c16 and 4f15 have been reported by
different methods previously, but no spectroscopic data (IR, 1H
NMR and 13C NMR) of the products were given.
On the other hand, recent interest in green chemistry has
posed a challenge in that new reaction conditions need to be
found which reduce the emission of volatile organic solvents
and the use of hazardous toxic chemicals.17 Sonication allows
the use of non-activated and crude reagents as well as an
aqueous solvent system; it is therefore friendly and non-toxic.
A control reaction was also carried out by using the
substrates 1a, 1e, 1f, 1g and 1j with conventional heating at
60 °C, which furnished the expected products in lower yields
and with much higher reaction times (35–300 min) (Table 1).
This study also revealed that using aryl aldehydes (1) with
electron donating groups on the aromatic ring required longer
Scheme 1 Synthesis of new derivatives of indenoquinolines.
* Correspondent. E-mail: m-chem41@guilan.ac.ir

236 JOURNAL OF CHEMICAL RESEARCH 2012
Table 1 Synthesis of indenoquinolines 4a–j under ultrasonic
7-(4-(Trifluoromethyl)phenyl)-8H-benzo[h]indeno[1,2-b]quinolin-
8-one (4b): Yellow solid; m.p. 290–292 °C. IR (KBr) (νmax, cm–1):
1711 (C=O), 1610, 1570 (C=C, C=N), 1325 (CF3). 1H NMR (500 MHz,
CDCl3): δ 7.53–7.50 (2H, m), 7.62 (2H, d, J = 7.92 Hz) 7.82–7.73
(5H, m), 7.84 (2H, d, J = 7.92 Hz), 7.91 (1H, d, J = 8.09 Hz), 8.27
(1H, d, J = 7.74 Hz), 9.57 (1H, d, J = 8.41 Hz) ppm. 13C NMR (125 MHz,
CDCl3): δ 191.2, 154.7, 146.6, 142.1, 140.0, 139.7, 136.4, 133.3, 132.0,
130.2, 129.0, 128.2, 126.6, 126.5, 126.4, 126.2, 126.1, 126.0, 125.7,
125.6, 124.7, 124.4, 124.2, 123.0, 120.1 ppm. Anal. Calcd for
C27H14F3NO(425.41): C, 76.23; H, 3.32; N, 3.29. Found: C, 76.12; H,
3.38; N, 3.17%.
irradiation at 60 °C
Entry
R
Time/min
Yield/%a
a
b
c
d
e
f
g
h
i
4-COOMe
4-CF3
4-F
10 (35)b
12
15
93 (63)b
91
85c
2-Cl
4-Cl
H
18
82
17 (60)b
20 (90)b
30 (120)b
35
83 (59)b
80 (56)b,c
78 (53)b
75
4-Me
4-iPr
7-(4-Fluorophenyl)-8H-benzo[h]indeno[1,2-b]quinolin-8-one( 4c):
Yellow solid; m.p. 231–235 °C (m.p. 300 °C)16. IR (KBr) (νmax, cm–1):
3-OH
4-OMe
60
73
75 (300)b
70 (46)b
1
j
1709 (C=O), 1603, 1572, 1504 (C=C, C=N), 1155 (C-F); H NMR
(500 MHz, CDCl3): δ 7.20 (2H, d, J = 8.62 Hz), 7.50–7.46 (3H, m),
7.57 (1H, d, J = 9.05 Hz), 7.80–7.69 (5H, m), 7.89 (1H, d, J = 7.19 Hz),
8.21 (1H, d, J = 7.98 Hz), 9.52 (1H, d, J = 8.07 Hz) ppm. 13C NMR
(125 MHz, CDCl3): δ 191.2, 162.2, 149.7, 146.8, 144.0, 137.3, 135.7,
134.9, 132.0, 131.9, 131.7, 129.8, 129.5, 128.3, 128.1, 127.7, 126.2,
125.5, 124.2, 123.8, 123.6, 122.0, 115.8 ppm. Anal. Calcd for
C26H14FNO (375.40): C, 83.19; H, 3.76; N, 3.73. Found: C, 83.28; H,
3.65; N, 3.61%.
a Identified by spectroscopic (IR, 1H NMR, 13C NMR) and elemental
analyses.
b Reaction under conventional heating at 60 °C.
cCompounds 4c and 4f have been prepared previously by differ-
ent procedures.15,16
reaction times and decreased the yields of the products (entries
4g–j), while the substrates with electron withdrawing groups
(entries 4a–d) were considerably accelerated in the rate of
the reaction.
In this study, no trace of an indeno-1,4-dihydroquinoline
which is formed as an intermediate in the course of the reac-
tion, could be detected, indicating that the intermediate is auto-
oxidised in situ to the related indenoquinoline. The reaction in
the presence of various solvents (EtOH, CHCl3, CH3CN, DMF,
1,4-dioxane, THF) at 60 °C compared to solvent-free condi-
tion furnished the desired products in much higher reaction
times and lower yields.
The structures of all products were confirmed by spectros-
copy (IR, 1H NMR, 13C NMR) and elemental analyses.
In conclusion, we have developed an efficient eco-friendly
protocol for the synthesis of new derivatives of indenoquino-
lines in a one-pot three-component approach by the reaction
of α-naphthylamine, arylaldehydes and indanedione under
solvent-free conditions, using ultrasonic irradiation as a green
source of energy. This procedure, furnished the desired inde-
noquinolines in lower reaction times (10–75 min) and higher
yields (70–93%) compared to conventional heating (Table 1).
7-(2-Chlorophenyl)-8H-benzo[h]indeno[1,2-b]quinolin-8-one
(4d):Yellow solid; m.p. 289–291 °C. IR (KBr) (νmax, cm–1): 1713 (C=O),
1
1576, 1529, 1468 (C=C, C=N), 1038 (C–Cl). H NMR (500 MHz,
CDCl3): δ 7.28 (2H, m), 7.44–7.41 (2H, m), 7.47 (1H, dt, J = 7.54,
1.57 Hz), 7.56 (1H, dd, J = 8.07, 0.96 Hz), 7.74–7.61 (5H, m), 7.83
(1H, d, J = 7.53 Hz), 8.18 (1H, d, J = 7.43 Hz), 9.45 (1H, d, J = 7.60 Hz)
ppm. 13C NMR (125 MHz, CDCl3): δ 190.8, 162.0, 149.7, 144.2,
137.3, 135.7, 135.0, 133.4, 133.3, 132.0, 131.7, 131.0, 130.6, 130.0,
129.7, 128.6, 128.2, 127.2, 127.1, 126.1, 125.2, 124.2, 123.9, 122.0
ppm. Anal. Calcd for C26H14ClNO (391.85): C, 79.69; H, 3.60; N,
3.57. Found: C, 79.47; H, 3.55; N, 3.47%.
7-(4-Chlorophenyl)-8H-benzo[h]indeno[1,2-b]quinolin-8-one
(4e): Yellow solid; m.p. 259–261 °C. IR (KBr) (νmax, cm–1): 1709
(C=O), 1572, 1520, 1485 (C=C, C=N), 1090 (C–Cl). 1H NMR
(400 MHz, CDCl3): δ 7.41 (2H, d, J = 8.40 Hz), 7.47 (1H, dt, J = 7.60,
0.80 Hz), 7.53 (1H, d, J = 9.20 Hz), 7.58 (1H, d, J = 8.40 Hz), 7.81–
7.66 (5H, m), 7.88 (1H, dd, J = 8.00 Hz), 8.18 (1H, d, J = 7.60 Hz),
9.48 (1H, d, J = 7.60 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ 190.8,
161.8, 149.3, 146.0, 143.6, 136.9, 135.3, 135.0, 134.4, 131.7, 131.3,
131.0, 129.4, 128.5, 127.9, 127.7, 127.3, 125.8, 124.8, 123.8, 123.7,
123.1, 121.5 ppm. Anal. Calcd for C26H14ClNO(391.85): C, 79.69; H,
3.60; N, 3.57. Found: C, 79.57; H, 3.65; N, 3.50%.
7-Phenyl-8H-benzo [h]indeno[1,2-b]quinolin-8-one (4f): Yellow
solid; m.p. 224–226 °C [m.p. 252 °C (decomp.)]15; IR (KBr) (νmax, cm–1):
1
1711 (C=O), 1614, 1572, 1512 (C=C, C=N). H NMR (500 MHz,
Experimental
CDCl3): δ 7.52–7.48 (3H, m), 7.63–7.61 (4H, m), 7.83–7.70 (5H, m),
7.91 (1H, d, J = 7.70 Hz), 8.25 (1H, d, J = 7.74 Hz), 9.56 (1H, d,
J = 8.10 Hz) ppm. 13C NMR (125 MHz, CDCl3): δ 191.2, 162.3,
149.6, 148.0, 144.1, 137.4, 135.6, 134.9, 133.8, 132.0, 131.7, 129.9,
129.7, 129.3, 128.6, 128.1, 127.6, 126.2, 125.6, 124.6, 124.2, 123.6,
121.9 ppm. Anal. Calcd for C26H15NO(357.41): C, 87.37; H, 4.23; N,
3.92. Found: C, 87.30; H, 4.11; N, 3.82%.
7-(p-Tolyl)-8H-benzo [h]indeno[1,2-b]quinolin-8-one (4g): Yellow
solid; m.p. 256–260 °C. IR (KBr) (νmax, cm–1): 1707 (C=O), 1608,
1572, 1502 (C=C, C=N), 1344 (C–H). 1H NMR (400 MHz, CDCl3): δ
2.54 (3H, s), 7.38 (2H, d, J = 8.00 Hz), 7.42 (2H, d, J = 8.00 Hz), 7.47
(1H, t, J = 7.40 Hz), 7.81–7.62 (5H, m), 7.88 (1H, d, J = 7.60 Hz),
8.20 (1H, d, J = 7.20 Hz), 9.52 (1H, d, J = 8.00 Hz) ppm. 13C NMR
(100 MHz, CDCl3): δ 191.2, 162.2, 149.5, 148.2, 144.0, 139.2, 137.4,
135.5, 134.9, 132.0, 131.6, 130.7, 130.0, 129.6, 129.3, 128.1, 128.0,
127.6, 126.2, 125.7, 124.7, 124.1, 123.6, 121.9, 22.0 ppm. Anal. Calcd
for C27H17NO (371.44): C, 87.31; H, 4.61; N, 3.77. Found: C, 87.23;
H, 4.69; N, 3.86%.
1H and 13C NMR spectra were recorded in CDCl3 (500 or 400 MHz)
with TMS as the internal reference. IR spectra were taken on a
Shimadzo IR-8900 spectrometer. Elemental analyses were done on a
Carlo-Erba EA111°CNNO-S analyser and agreed with the calculated
values. The progress of the reactions was checked by TLC on silicagel
60H, F254, Art No. 7730. For the ultrasound reactions, ultrasound
apparatus Astra 3D (9.5 L, 45 kHz frequency, input power with heating,
305 W, two transducers, from TECNO-GAZ was used.
Synthesis of 4a–j under ultrasound irradiation; general procedure
A mixture of α-naphthylamine (0.1432 g, 1 mmol), indanedione (0.146 g,
1 mmol), and respective arylaldehydes (1 mmol) was taken in a 50 mL
flask and was irradiated in a water bath under silent condition by
ultrasound (45 KHz) at 60 °C for the required reaction times (Table 1).
The reaction mixture was purified by recrystallisation from ethanol
to obtain the pure products of 4a–j (Table 1).
Methyl 4-(8-oxo-8H-benzo[h]indeno[1,2-b]quinolin-7-yl)benzoate
(4a):Yellow solid; m.p. 310–314 °C. IR (KBr) (νmax, cm–1): 1718 (C=O),
1
7-(4-Isopropylphenyl)-8H-benzo[h]indeno[1,2-b]quinolin-8-one
1610, 1576, 1464 (C=C, C=N), 1277 (C–O). H NMR (500 MHz,
(4h): Yellow solid; m.p. 278–280 °C; IR (KBr) (νmax, cm–1): 1713
CDCl3): δ 4.04 (3H, s), 7.51 (2H, t, J = 7.15 Hz), 7.57 (2H, d, J = 6.61 Hz),
7.83–7.71(5H, m), 7.91(1H, d, J = 7.23 Hz), 8.26(1H, d, J = 7.68 Hz),
8.29 (2H, d, J = 6.60 Hz), 9.55 (1H, d, J = 8.07 Hz) ppm. 13C NMR
(125 MHz, CDCl3): δ 190.9, 167.1, 162.0, 149.6, 146.4, 144.0, 138.6,
137.2, 135.7, 134.8, 131.8, 131.7, 130.8, 130.0, 129.8, 128.4, 128.1,
127.7, 126.1, 125.0, 124.1, 124.0, 123.4, 121.9, 52.7 ppm. Anal. Calcd
for C28H17NO3 (415.45): C, 80.95; H, 4.12; N, 3.37. Found: C, 80.78;
H, 4.02; N, 3.26%.
1
(C=O), 1600, 1574, 1501, 1464 (C=C, C=N), 1342 (C–H). H NMR
(500 MHz, CDCl3): δ 1.43 (6H, d, J = 6.93 Hz), 3.11 (1H, sept),
7.43 (2H, d, J = 8.10 Hz), 7.48 (2H, d, J = 8.10 Hz), 7.51 (1H, t,
J = 7.47 Hz), 7.82–7.68 (6H, m), 7.90 (1H, d, J = 7.58 Hz), 8.28 (1H,
d, J = 7.36 Hz), 9.57 (1H, d, J = 8.10 Hz) ppm. 13C NMR (125 MHz,
CDCl3): δ 191.2, 162.3, 150.0, 149.5, 148.5, 144.0, 137.5, 135.6,
135.0, 131.9, 131.7, 130.9, 130.1, 129.7, 128.1, 128.0, 127.6, 126.6,

JOURNAL OF CHEMICAL RESEARCH 2012 237
126.3, 125.8, 124.8, 124.2, 123.7, 122.0, 34.5, 24.4 ppm. Anal. Calcd
for C29H21NO (399.49): C, 87.19; H, 5.30; N, 3.51. Found: C, 87.33;
H, 5.21; N, 3.58%.
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1707 (C=O), 1606, 1581, 1520, 1452 (C=C, C=N), 1223 (C–O). H
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NMR (500 MHz, CDCl3): δ 6.77 (1H, dd, J = 7.44, 1.06 Hz), 6.81
(1H, t, J = 1.93 Hz), 6.95 (1H, dd, J = 7.14, 0.86 Hz), 7.27 (1H, t,
J = 7.86 Hz), 7.39 (1H, t, J = 6.41 Hz), 7.78–7.52 (6H, m), 8.11 (1H,
d, J = 7.45 Hz), 9.41 (1H, d, J = 8.34 Hz) ppm. 13C NMR (125 MHz,
CDCl3): δ 191.2, 158.7, 154.5, 146.4, 144.0, 143.9, 139.7, 138.1,
136.4, 135.5, 135.4, 135.1, 134.9, 131.6, 129.6, 128.1, 128.0, 127.5,
127.2, 126.1, 125.6, 124.8, 124.0, 121.9, 120.7, 117.0, 116.4 ppm.
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Found: C, 83.46; H, 4.14; N, 3.62%.
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(4j): Yellow solid; m.p. 278–281 °C. IR (KBr) (νmax, cm–1): 1711
1
(C=O), 1607, 1572, 1502, 1460 (C=C, C=N), 1277 (C–O). H NMR
(500 MHz, CDCl3): δ 3.98 (3H, s), 7.15 (2H, d, J = 8.32 Hz), 7.45
(2H, d, J = 8.32 Hz), 7.48 (1H, t, J = 7.40 Hz), 7.81–7.67 (6H, m),
7.89 (1H, d, J = 7.69 Hz), 8.21 (1H, d, J = 7.34 Hz), 9.52 (1H, d,
J = 8.06 Hz) ppm. 13C NMR (125 MHz, CDCl3): δ 191.4, 162.4,
160.6, 149.7, 148.0, 144.1, 137.5, 135.5, 134.9, 132.0, 131.7, 131.6,
129.6, 128.0, 127.9, 127.6, 126.2, 125.8, 125.6, 124.7, 124.1, 123.6,
121.8, 114.0, 55.7 ppm. Anal. Calcd for C27H17NO2 (387.44): C, 83.70;
H, 4.42; N, 3.61. Found: C, 83.62; H, 4.31; N, 3.52%.
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Received 29 January 2012; accepted 18 February 2012
Paper 1201136 doi: 10.3184/174751912X13319177859559
Published online: 17 April 2012

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