Microwave-assisted, regioselective one-pot synthesis of quinolines and bis-quinolines catalyzed by Bi(III) immobilized on triazine dendrimer stabilized magnetic nanoparticles

Article abstract of DOI:10.1016/j.tetlet.2016.11.102

Fe₃O₄-TDSN-Bi(III) was utilized as an efficient and reusable catalyst for the regioselective one-pot synthesis of quinoline derivatives from arylamines, arylaldehydes and methyl propiolate under microwave irradiation and solvent-free conditions. Also, bis-quinolines were obtained in high yields from dialdehydes or diamines. Atom-economy, high to excellent yields, easy work-up, as well as simple catalyst recovery and reusability are the key features of this procedure.

Full text of DOI:10.1016/j.tetlet.2016.11.102

Accepted Manuscript
Microwave-assisted, regioselective one-pot synthesis of quinolines and bis-qui-
nolines catalyzed by Bi(III) immobilized on triazine dendrimer stabilized mag-
netic nanoparticles
Beheshteh Asadi, Amir Landarani-Isfahani, Iraj Mohammadpoor-Baltork,
Shahram Tangestaninejad, Majid Moghadam, Valiollah Mirkhani, Hadi Amiri
Rudbari
PII:
S0040-4039(16)31593-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.11.102
TETL 48388
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
1 October 2016
21 November 2016
23 November 2016
Please cite this article as: Asadi, B., Landarani-Isfahani, A., Mohammadpoor-Baltork, I., Tangestaninejad, S.,
Moghadam, M., Mirkhani, V., Amiri Rudbari, H., Microwave-assisted, regioselective one-pot synthesis of
quinolines and bis-quinolines catalyzed by Bi(III) immobilized on triazine dendrimer stabilized magnetic
nanoparticles, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.11.102
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Tetrahedron Letters
Microwave-assisted, regioselective one-pot synthesis of quinolines and bis-quinolines
catalyzed by Bi(III) immobilized on triazine dendrimer stabilized magnetic
nanoparticles
Beheshteh Asadi, Amir Landarani-Isfahani, Iraj Mohammadpoor-Baltork*, Shahram Tangestaninejad,
Majid Moghadam, Valiollah Mirkhani, Hadi Amiri Rudbari
Department of Chemistry, Catalysis Division, University of Isfahan, Isfahan 81746-73441, Iran
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Fe3O4-TDSN-Bi(III) was utilized as an efficient and reusable catalyst for the regioselective one-
pot synthesis of quinoline derivatives from arylamines, arylaldehydes and methyl propiolate
under microwave irradiation and solvent-free conditions. Also, bis-quinolines were obtained in
high yields from dialdehydes or diamines. Atom-economy, high to excellent yields, easy work-
up, as well as simple catalyst recovery and reusability are the key features of this procedure.
Available online
Keywords:
Quinoline
Bismuth
Microwave irradiation
Multicomponent reaction (MCR)
Dendrimers
———
* Corresponding author. Tel.: +98-31-37932749; fax: +98-31-36689732; e-mail address: imbaltork@sci.ui.ac.ir (I. Mohammadpoor-Baltork)

2
Tetrahedron
1. Introduction
conventional heating, the model reaction was repeated using
conventional heating (85 °C) to give the desired product in 40%
yield after 4 hours (Entry 18). This confirmed that the increase in
reaction rate was primarily due to the effect of MW irradiation.
According to Table 1, the optimal reaction conditions were 1-
naphthylamine (1 mmol), 4-fluorobenzaldehyde (1 mmol) and
methyl propiolate (1.5 mmol) in the presence of Fe3O4-TDSN-
Bi(III) (8 mol%, 133 mg) at 360 W, 85 °C.
Multicomponent reactions (MCRs) have recently gained
significant attention owing to the wide range of applications in
synthesis. These reactions possess valuable advantages over
conventional linear syntheses, allowing the formation of several
bonds and the construction of novel and complex molecular
structures from simple precursors with a minimum number of
synthetic steps.1
To examine the scope of this methodology, 1-naphthylamine
and methyl propiolate were treated with a wide range of
arylaldehydes containing electron-withdrawing and electron-
donating substituents at the ortho-, meta-, and para-positions of
the aromatic ring under MW irradiation to afford the
corresponding benzo[h]quinoline-3-carboxylate derivatives. The
electronic nature of the substituents on the aromatic ring had little
influence on the reaction process (Scheme 1, 4a-i). Likewise,
substituted anilines reacted well with various arylaldehydes and
methyl propiolate to furnish the corresponding quinoline-3-
carboxylate derivatives in high yields (Scheme 1, 4j-o).
Quinolines are an important class of heterocyclic compounds
possessing potent biological activities including anticancer,2
antimalarial,3 antiasthmatic,4 antidiabetic,5 antibacterial,6
antileishmaniasis,7 and antitumor8 properties. Additionally, this
skeleton is found in natural products and is the main structural
unit of several agrochemicals,9 and dye-sensitized solar cells.10
Representative functionalized quinoline based drugs include
camptothecin (anticancer)11 and cryptolepine (antimalarial).12
Many synthetic methods for the preparation of quinolines
have been reported in the literature,13 however, some of these
approaches require either high temperatures, harmful organic
solvents, strongly acidic media and/or non-reusable catalysts.
Furthermore, in some cases high catalyst loadings (up to 30
mol%) are necessary to achieve reasonable yields.
Table 1. Influence of Reaction Parameters on the Yield of 4a.
Although there are
a few reports dealing with the
regioselective preparation of 2,3-disubstituted quinolines,14 it is
still necessary to develop additional methods.
Entry
1
Catalyst (mol%)
-
T (oC)
85
Time (min)
30
Yield 4a (%)a
Recently, we reported Fe3O4-TDSN-Bi(III) as an efficient and
recyclable catalyst for the synthesis of aminonaphthoquinones, as
0
2
ZnCl2 (8)
85
85
85
85
85
85
85
85
85
85
75
95
85
85
85
85
85
2
20
25
15
50
35
40
72
97
97
70
80
97
97
97
81
70
40
well
as
symmetric
and
unsymmetric
bis-
aminonaphthoquinones.15 In a continuation of our research on the
applications of this catalyst and the synthesis of quinoline
derivatives,16 herein, we report an efficient microwave-assisted,
regioselective synthesis of quinolines, as well as symmetric and
unsymmetric bis-quinolines, using a one-pot, three-component
reaction between arylamines, arylaldehydes and methyl
propiolate catalyzed by Fe3O4-TDSN-Bi(III) under solvent-free
conditions.
3
MnCl2 (8)
2
4
AlCl3 (8)
2
5
FeCl3 (8)
2
6
BiCl3 (8)
2
7
Bi(NO3)3·5H2O (8)
Bi(OTf)3 (8)
2
8
2
2. Results and Discussion
9
Fe3O4-TDSN-Bi(III) (8)
Fe3O4-TDSN-Bi(III)(10)
Fe3O4-TDSN-Bi(III) (6)
Fe3O4-TDSN-Bi(III) (8)
Fe3O4-TDSN-Bi(III) (8)
Fe3O4-TDSN-Bi(III) (8)
Fe3O4-TDSN-Bi(III) (8)
Fe3O4-TDSN-Bi(III) (8)
Fe3O4-TDSN-Bi(III) (8)
Fe3O4-TDSN-Bi(III) (8)
2
The Fe3O4-TDSN-Bi(III) catalyst was prepared according to
our previously reported procedure.15 At the outset of this study,
the reaction of 1-naphthylamine 1, 4-fluorobenzaldehyde 2 and
methyl propiolate 3 was investigated for optimization of the
reaction conditions (Table 1). The reaction was first performed in
the absence of catalyst under microwave (MW) irradiation17 (360
W) at 85 °C in order to explore the role of catalyst. Under these
conditions, no product was observed, even after 30 min (Entry 1).
The reaction was then examined in the presence of 8 mol% of
various Lewis acids including ZnCl2, MnCl2, AlCl3, FeCl3, BiCl3,
Bi(NO3)3∙5H2O and Bi(OTf)3 for 2 min (Entries 2-8). These
catalysts were only moderately effective, giving the desired
product in 15-72% yield. An improved yield was observed when
Fe3O4-TDSN-Bi(III) was used, and the desired product was
obtained in 97% yield (Entry 9). Next, reaction parameters such
as the catalyst loading, temperature, reaction time, and MW
power were optimized. Accordingly, the reaction was repeated
under solvent-free conditions and MW irradiation with different
catalyst loadings (Entries 9-11), and the maximum yield (97%)
was observed with 8 mol% of catalyst (Entry 9). The effect of
temperature was studied by carrying out the model reaction at
different temperatures and the best results were obtained at 85 °C
(Entries 9 and 12). Increasing the temperature to 95 °C had no
effect on the yield (Entry 13). Extending the reaction time (Entry
14) and the MW power (Entry 15) also did not improve the yield,
while decreasing these parameters resulted in lower yields
(Entries 16 and 17). To probe the effect of MW irradiation versus
10
11
12
13
14
15 b
16
17 c
18 d
2
2
2
2
5
2
1
2
240
a Isolated yield. b Reaction performed with an applied power of 420 W. c Reaction
performed with an applied power of 300 W. d Reaction carried out under
conventional heating conditions.

Scheme 3. Synthesis of a symmetric bis-quinoline from diamine catalyzed
by Fe3O4-TDSN-Bi(III).
Importantly, the reaction of terephthaldialdehyde with two
different amines and methyl propiolate gave the related
unsymmetric bis-quinoline 8a in 72% yield (Scheme 4).
Scheme 4. Synthesis of a unsymmetric bis-quinoline catalyzed by Fe3O4-
TDSN-Bi(III).
1
The products were identified by FT-IR, MS, H NMR and
13C NMR spectra as well as elemental analysis. Additionally,
the structures of 4d (CCDC 1478724) and 4h (CCDC
1478723) were confirmed by single crystal X-ray analysis
(Fig. 1, ESI Tables 1-4). The products were obtained by
recrystallization from EtOH and dried under reduced pressure.
Scheme 1. Scope of the quinoline synthesis catalyzed by Fe3O4-TDSN-
Bi(III).
The product formation can take place via two
pathways,13j,14a leading to either 2-substituted-quinoline-3-
carboxylates or 2-substituted-quinoline-4-carboxylates. The
reaction in the presence of Fe3O4-TDSN-Bi(III) afforded 2-
substituted-quinoline-3-carboxylate products which were
confirmed by NMR spectra and single crystal X-ray studies. A
possible mechanism for formation of the quinolines, which
involves air, is discussed in the ESI. Note that, 2-substituted-
quinoline-3-carboxylate derivatives have an added advantage
of being able to undergo nucleophilic substitution at the 4-
position owing to blocking of the 2-position compared to the
2-substituted-quinoline-4-carboxylate derivates.18
Benzo[h]quinoline-3-carboxylate derivatives were rapidly
accessible on gram scales. On
a 10 mmol scale, 1-
naphthylamine, reacted with 4-fluorobenzaldehyde and methyl
propiolate in the presence of Fe3O4-TDSN-Bi(III) (0.8 mol%)
at 360 W, 85 °C, to give benzo[h]quinoline-3-carboxylate 4a
in 70% yield after 25 min.
Encouraged by this success, we next turned our attention to
extending the substrate scope of this reaction to access bis-
quinolines. The reaction of dialdehydes including
terephthaldialdehyde and isophthaldialdehyde with arylamines
and methyl propiolate proceeded rapidly to give the
corresponding symmetric bis-quinolines 6a-c in high yields
(Scheme 2).
Scheme 2. Synthesis of symmetric bis-quinolines from dialdehydes
catalyzed by Fe3O4-TDSN-Bi(III).
In another approach for the synthesis of bis-quinolines,
treatment of 4,4'-diaminodiphenylmethane with benzaldehyde
and methyl propiolate gave the desired symmetric bis-
quinoline 7a in 72% yield (Scheme 3).
Figure 1. Molecular structures of (a) 4d and (b) 4h. Non-H atoms
are represented as 30% probability displacement ellipsoids.

4
Tetrahedron
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Catalyst recovery and reusability is an important property of
this catalyst. The reusability of Fe3O4-TDSN-Bi(III) was probed
in the synthesis of 4a. Upon reaction completion, the mixture was
cooled to room temperature and diluted with cold ethanol. The
catalyst was separated using an external magnet, washed several
times with ethanol, dried and then reused for subsequent
reactions. The catalyst could be reused at least 6 times without
considerable loss of activity (Table 2). No quantifiable amount of
leached bismuth from the Fe3O4-TDSN-Bi(III) catalyst was
detected (˂1%) as determined by ICP-OES. This excellent
reusability and high activity clearly show that the catalyst is
stable under the reaction conditions.
Table 2. Reusability of the Fe3O4-TDSN-Bi(III) catalyst in the
synthesis of 4a.a
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Yield (%)b
97
97
96
94
94
92
92
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following items: Micro-SYNTH labstation, equipped with a glass
door, a dual magnetron system with pyramid-shaped diffuser,
1000 W delivered power, exhaust system, magnetic stirrer,
‘‘quality pressure’’ sensor for fla able or anic solvents, and a
ATCFO fibre optic system for automatic temperature control.
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a
Reaction conditions: 1-naphthylamine (1 mmol), 4-fluorobenzaldehyde (1 mmol),
methyl propiolate (1.5 mmol), Fe3O4-TDSN-Bi(III) (8 mol%, 133 mg), 360 W, 85 oC.
Isolated yield.
b
In summary, we have developed an efficient microwave-
promoted synthesis of quinoline derivatives via a one-pot, three-
component reaction of arylamines, arylaldehydes and methyl
propiolate using Fe3O4-TDSN-Bi(III) as
a
recoverable
heterogeneous catalyst. Additionally, this catalytic system was
used for the multicomponent synthesis of symmetric and
unsymmetric bis-quinolines. To date, this is the first report on the
regioselective synthesis of symmetric and unsymmetric bis-
quinolines via
a
one-pot, multicomponent reaction of
dialdehydes/diamines under MW irradiation and solvent-free
conditions, and therefore, can be considered as a useful method
for the preparation of these compounds. This method presents
several distinctive advantages, such as high reaction rates, high to
excellent yields, a simple work-up procedure and easy recovery
of the catalyst.
Acknowledgments
The authors are grateful to the Research Council of the
University of Isfahan for financial support of this work.
Supplementary data
Supplementary data (general procedure and copies of H and 13C
NMR spectra of the products) associated with this article can be
found in the online version at ….
1
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Microwave-assisted, regioselective one-pot
synthesis of quinolines and bis-quinolines
catalyzed by Bi(III) immobilized on triazine
dendrimer stabilized magnetic nanoparticles
Leave this area blank for abstract info.
Beheshteh Asadi, Amir Landarani-Isfahani, Iraj Mohammadpoor-Baltork,* Shahram Tangestaninejad, Majid
Moghadam, Valiollah Mirkhani, Hadi Amiri Rudbari

Highlights
 Fe3O4-TDSN-Bi(III) was applied to the regioselective one-pot synthesis of quinolines.
 Bis-quinolines were obtained from dialdehydes or diamines.
 The catalyst could be separated and reused six times without a decrease in activity.