Simple route to indeno[1,2-b]quinoline derivatives via a coupling reaction catalyzed by TiO2 nanoparticles

Article abstract of DOI:10.1016/j.cclet.2013.02.017

A simple, efficient and high yielding approach for the synthesis of indeno[1,2-b]quinolinediones has been developed by a one-pot, four-component, coupling reaction utilizing TiO₂ nanoparticles (TiO₂-NPs) as a heterogeneous catalyst at 80 °C in aqueous media.

Full text of DOI:10.1016/j.cclet.2013.02.017

Chinese Chemical Letters 24 (2013) 318–320
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Chinese Chemical Letters
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Original Article
Simple route to indeno[1,2-b]quinoline derivatives via a coupling reaction
catalyzed by TiO2 nanoparticles
Shahrzad Abdolmohammadi
Department of Chemistry, Faculty of Science, East Tehran Branch, Islamic Azad University, PO Box 33955-163, Tehran, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
A simple, efficient and high yielding approach for the synthesis of indeno[1,2-b]quinolinediones has
been developed by a one-pot, four-component, coupling reaction utilizing TiO2 nanoparticles (TiO2-NPs)
as a heterogeneous catalyst at 80 8C in aqueous media.
Received 6 December 2012
Received in revised form 29 January 2013
Accepted 2 February 2013
Available online 15 March 2013
ß 2013 Shahrzad Abdolmohammadi. Published by Elsevier B.V. on behalf of Chinese Chemical
Society. All rights reserved.
Keywords:
Aqueous media
Indeno[1,2-b]quinoline
Reusability of catalyst
TiO2 nanoparticles
1. Introduction
The indenoquinoline derivatives play a prominent role in
medicinal chemistry by possessing
a diverse spectrum of
In the last few years, nanoscale inorganic solid oxides as
catalysts have gained great importance in surface synthetic
organic chemistry, due to the good activation of adsorbed
compounds, enhancement of reaction rates, simplicity of opera-
tion, reusability of the catalyst, and readily available at low cost
[1–3]. Nanoscale heterogeneous catalysts offer higher surface
area and low coordination sites, which are responsible for the
higher catalytic activity [4–9]. The catalysts with the most
preferred surfaces would be those, which are easy to handle,
inexpensive, non-toxic and easily removed during work-up. TiO2
nanoparticles (TiO2-NPs) as an inexpensive, non-toxic, moisture
stable, reusable, commercially available white powder is of great
interest to many scientists in the recent years. In general, several
similar applications of this nanoscale method, as an effective
catalyst in green synthetic organic chemistry, have already been
highlighted in the literature [10–17]. It has been my interest to
develop a novel, simple method for the synthesis of indeno[1,2-
b]quinolinediones 5(a–j) by a one-pot, four-component coupling
reaction of 1,3-indanedione (1), aromatic aldehydes (2), primary
amines (3) and dimedone (4). This method should be successfully
accomplished by using commercially available TiO2-NPs with an
average size of 20 nm, as catalyst in aqueous media (Scheme 1).
biological properties, such as antitumor [18,19], acetylcholines-
terase inhibitors [20], antimalarials [21], steroid reductase
inhibitors [22] in addition to potential new topo y/yy inhibitor
activities [23,24]. Therefore, the preparation of this heterocyclic
nucleus is of particular importance to both organic and medicinal
chemists [25–28]. Previous methods for the synthesis of
indeno[1,2-b]quinolinediones have been reported [29–33]. How-
ever, despite the potential utility of these existing methods, many
have displayed drawbacks. Our new approach provides noticeable
benefits as TiO2 is non-toxic inexpensive, work-up is simple, and
uses a four-component reaction for the synthesis of these
compounds, which could improve the bond forming efficiency
and atom economy.
2. Experimental
General procedure for preparation of compounds 5a–j: A mixture
of 1,3-indanedione (1, 1 mmol), aromatic aldehydes (2, 1 mmol),
primary amines (3, 1 mmol), dimedone (4, 1 mmol) and TiO2 NPs
(7.9 mg, 10 mol%) was stirred at 80 8C in water (10 mL) for 2 h.
After completion of the reaction (monitored by TLC), the reaction
mixture filtered and the solid mass was then diluted with DMF
(5 mL), and the mixture was centrifuged at 2000–3000 rpm for
5 min to remove the TiO2-NPs catalyst. The organic solution was
then poured into cold water (15 mL), filtered and washed with
E-mail addresses: abdolmohamadi_sh@yahoo.com, s.abdolmohamadi@iauet.ac.ir.
1001-8417/$ – see front matter ß 2013 Shahrzad Abdolmohammadi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.02.017

[
S. Abdolmohammadi / Chinese Chemical Letters 24 (2013) 318–320
319
O
Table 2
TiO2-NPs catalyzed synthesis of indeno[1,2-b]quinolinediones 5(a–j) in water at
80 8C.
Ar
H
Ar
O
O
O
O
O
2
Yield (%)a
MP (8C)
TiO2 Nanoparticles
H2O, 80 0
Product
Ar
R
+
C
CH3
CH3
CH3
CH3
Obs.
Lit.
O
N
R
228–23030
255–25629
280–28331
271–27331
263–26531
295–29730
220–22230
230–23330
283–28529
268–27030
RNH2
5a
5b
5c
5d
5e
5f
4-BrC6H4
CH3
97
96
96
98
97
98
95
96
95
98
230–231
254–256
279–281
272–274
264–266
296–298
222–224
231–233
281–283
269–271
1
4
4-BrC6H4
4-CH3C6H4
C6H5
3
5
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-CH3C6H4
Cyclopropyl
Cyclopropyl
CH3
Scheme 1. Synthesis of indeno[1,2-b]quinolinedione derivatives.
2-ClC6H4
4-ClC6H4
5g
5h
5i
4-CH3OC6H4
4-CH3OC6H4
4-CH3C6H4
4-NO2C6H4
Table 1
The synthesis of 5a from 1,3-indanedione, 4-bromobenzaldehyde, methylamine
4-CH3C6H4
Cyclopropyl
and dimedone under different conditions.
5j
Yield (%)a
a
Entry
Solvent
Catalyst (mol%)
Temp. (8C)
Time (h)
Yields refer to those of pure isolated products.
1
2
Neat
H2O
No catalyst
80
80
80
80
80
80
90
80
100
70
90
9
8
4
2
2
2
4
4
7
3
2
trace
54
82
97
97
83
71
68
88
91
98
No catalyst
H
Ar), 7.34 (m, 2H, HAr),7.40 (d, 2H, 3J = 8.5 Hz, HAr), 7.45 (m, 1H,
HAr), 7.66 (d, 1H, 3J = 7.5 Hz, HAr). 13C NMR (125 MHz, DMSO-d6):
3
H2O
TiO2-NPs (5%)
TiO2-NPs (10%)
TiO2-NPs (20%)
TiO2-NPs (10%)
TiO2-NPs (10%)
TiO2-NPs (10%)
TiO2-NPs (10%)
TiO2-NPs (10%)
TiO2-NPs (10%)
4
H2O
d
5
H2O
30.8, 33.6, 36.4, 40.1, 42.4, 48.5, 102.3, 115.4, 122.3, 123.2, 123.8,
126.1, 126.7, 128.1, 130.9, 131.4, 134.9, 141.3, 143.2, 144.9, 181.7,
194.6. Anal. Calcd. for C25H22BrNO2 (448.36): C 66.97, H 4.95, N
3.12; found: C 66.84, H 5.07, N 3.06.
6
Neat
CH3CN
CH2Cl2
DMF
H2O
7
8
9
10
11
H2O
3. Results and discussion
a
Isolated yield.
Initially, 4-bromobenzaldehyde was chosen as a model for the
reaction with 1,3-indanedione, methylamine and dimedone to
afford 10-(4-bromophenyl)-5,7,7-trimethyl-6,7,8,10-tetrahydro-
5H-indeno[1,2-b]quinoline-9,11-dione 5a under several condi-
tions (Table 1). The optional result was obtained when 10 mol% of
TiO2-NPs had been used in aqueous media (entry 4).
aqueous ethanol and then dried at 80 8C for several hours in vacuo
to afford the pure products 5 (Scheme 1).
Selected spectral data: 10-(4-Bromophenyl)-5,7,7-trimethyl-
6,7,8,10-tetrahydro-5H-indeno[1,2-b]quinoline-9,11-dione
(5a):
Yield 435 mg (97%). Orange powder. Mp 230–231 8C. IR (KBr,
cmÀ1): nmax 3004, 2947, 2859, 1671, 1636, 1624, 1544. 1H NMR
To demonstrate the utility of this method, some benzalde-
hydes with various functionalities and primary amines with
different substitutents were employed successfully to produce
corresponding products in high yields (Table 2). The structures of
the synthesized compounds 5(a–j) were confirmed by their
(500 MHz, DMSO-d6): d 1.00 (s, 3H, CH3), 1.07 (s, 3H, CH3), 2.17 (m,
2H, CH2), 2.54 (d, 1H, 2J = 17.0 Hz, CH2), 2.91 (d, 1H, 2J = 17.0 Hz,
CH2), 3.73 (s, 3H, NCH3), 4.78 (s, 1H, H-10), 7.17 (d, 2H, 3J = 8.5 Hz,
[(Schme_2)TD$FIG]
O
O
O
O
+
TiO2
H
O
O
TiO2 NPs
TiO2 NPs
+
Ar
H
Ar
-H
TiO2
1
6
7
2
-TiO2 NPs
-H2O
O
Ar
O
O
O
1) Michael addition
2) Tautomerization
O
RNH2
3
3) -TiO2 NPs
Ar
O
HN
R
HN
R
O
O
+
TiO2
10
4
8
9
Ar
O
Ar
N
O
O
O
-H2O
N
R
5
OH
R
11
Scheme 2. Proposed mechanism for the synthesis of indeno[1,2-b]quinolinediones catalyzed by TiO2-NPs in aqueous media.

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S. Abdolmohammadi / Chinese Chemical Letters 24 (2013) 318–320
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According to both Lewis acid and Lewis base characteristics of
metal oxides,
a plausible mechanism for the formation of
indeno[1,2-b]quinolinediones 5 is presented in Scheme 2. It is
not unreasonable to assume that TiO2-NPs catalyzes the formation
of carbocation 7 which then undergoes a Knoevenagel condensa-
tion with enolized 1,3-indanedione 6, producing the alkene 8. The
enamine 9, obtained by the reaction of of dimedone 4 with primary
amine 3, then adds to alkene 8 to produce the Michael adduct 10.
Intramolecular cyclization of 10 gives product 5, after dehydration
of intermediate 11.
To check the viability of the catalyst, after the completion of the
model reaction, the resulting product 5a was treated with DMF and
the catalyst removed by filtration. It was repeatedly washed with
water, dried in vacuo and reused for successive reaction. It was
determined that the catalyst can be recycled for at least four cycles
without any change in activity.
4. Conclusion
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In summary, a highly efficient and environmentally green
methodology for the synthesis of indeno[1,2-b]quinolinedione
derivatives via the one-pot four-component coupling reaction of
1,3-indanedione, aromatic aldehydes, primary amines, and dime-
done has been developed. The attractive features of this protocol
are the simple reaction procedure, short reaction time, easy work-
up, reusability of TiO2-NPs catalyst, and high product yields. To the
best of our knowledge, this is the first report on the synthesis of
indeno[1,2-b]quinolinedione derivatives by a four-component
reaction using TiO2-NPs as a catalyst.
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8
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Acknowledgment
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Shahrzad Abdolmohammadi thanks the Research Council of
East Tehran Branch, Islamic Azad University for financial support of
this work.
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