Synthesis of Quinolines and Pyrido[3,2- g or 2,3- g]quinolines Catalyzed by Heterogeneous Propylphosphonium Tetrachloroindate Ionic Liquid

Article abstract of DOI:10.1021/acs.joc.8b02261

This report explains an efficient method for synthesis of an array of quinolines via the reaction of 2-aminoaryl ketones with terminal and internal alkynes in the presence of propylphosphonium tetrachloroindate ionic liquid supported on nanosilica (PPInCl

Full text of DOI:10.1021/acs.joc.8b02261

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Note
Synthesis of Quinolines and Pyrido[3,2-g or 2,3-g]quinolines Catalyzed
by Heterogeneous Propylphosphonium Tetrachloroindate Ionic Liquid
Mahboobeh Azizi, Mahboobeh Nasr-Esfahani, Iraj Mohammadpoor-Baltork,
Majid Moghadam, Valiollah Mirkhani, Shahram Tangestaninejad, and Reza Kia
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02261 • Publication Date (Web): 06 Nov 2018
Downloaded from http://pubs.acs.org on November 7, 2018
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Synthesis of Quinolines and Pyrido[3,2-g or 2,3-
g]quinolines Catalyzed by Heterogeneous
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Propylphosphonium Tetrachloroindate Ionic Liquid
Mahboobeh Azizi†, Mahboobeh Nasr-Esfahani†, Iraj Mohammadpoor-Baltork*,†, Majid Moghadam†,
Valiollah Mirkhani†, Shahram Tangestaninejad†, and Reza Kia‡
†Department of Chemistry, Catalysis Division, University of Isfahan, Isfahan 81746-73441, Iran
‡ Chemistry Department, Sharif University of Technology, P.O. Box 11155-3516, Tehran, Iran
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AUTHOR EMAIL ADDRESS
imbaltork@sci.ui.ac.ir
CORRESPONDING AUTHOR FOOTNOTE
†Department of Chemistry, Catalysis Division, University of Isfahan, Isfahan 81746-73441, Iran
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ABSTRACT
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This report explains an efficient method for synthesis of an array of quinolines, via the reaction of 2-
aminoaryl ketones with terminal and internal alkynes in the presence of propylphosphonium
tetrachloroindate ionic liquid supported on nano-silica (PPInCl-nSiO2) as a heterogeneous and reusable
catalyst under solvent-free conditions. Inspired by this catalytic system, the first easy one-step synthesis
of symmetric and unsymmetric pyrido[3,2-g or 2,3-g]quinolines was investigated through the reaction
of diaroylphenylenediamines with one alkyne or two different alkynes.
Quinolines are an important class of nitrogen containing heterocycles, which has been investigated
extensively in terms of biological activities, medicinal applications, electric and photonic usages.1 Due
to their importance, several methods such as Skraup, Combes, Friedlander and Doebner–Von have been
reported for the synthesis of quinolines.2 Recently, the condensation of 2-aminoaryl ketones and alkynes
in the presence of various catalysts and reagents under different reaction conditions have also been used
fot the synthesis of these compounds.3 However, some of the reported methods suffer from one or more
of the disadvantages such as the use of toxic reagents and solvents, costly catalysts, unsatisfactory
reaction times and yields, large amounts of catalysts, tedious workup and lack of recovery and reuse of
the catalyst from homogenous reaction mixture. More importantly, the simple quinoline derivatives are
mostly synthesized by these procedures. In addition, during the past years, little attention has been paid
to the synthesis of pyrido[3,2-g]quinolines and pyrido[2,3-g]quinolines, and only a few reports
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involving harsh conditions and multi-steps reactions are available for the prepartation of some
derivatives of thes heterocycles4 (Scheme 1).
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In continuation of our interest on the constraction of quinoline deriveitives using heterogeneous
catalysts,5 herein, we describe a straightforward method for the synthesis of various substituted
quinolines, novel quinolines containing one 2-aminoaryl ketone unit in the backbone, novel symmetric
and unsymmetric pyrido[3,2-g or 2,3-g]quinolines using propylphosphonium tetrachloroindate ionic
liquid supported on nano-silica (PPInCl-nSiO2) as an efficient heterogeneous catalyst under solvent-free
conditions (Scheme 1).
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Scheme 1. Some examples and the proposed strategy for synthesis of pyrido[3,2-g]quinolines
and pyrido[2,3-g]quinolines
This work
N
N
N
N
N
H2N
NH2
N
+
Pyrido[2,3-g]quinoline
Pyrido[3,2-g]quinoline
PhOC
COPh
Ph
Ar
Ph
N
Previous methods
ArOC
H2N
NH2
H2N
NH2
H3C
N
N
CH3
[4a]
+
(CH3CO)2CH2
+
COAr
N
OHC
CHO
H3COC
COCH3
Ar
N
N
Ar
OHC
NO2
6 Steps
[4b]
ArOC
H2N
NH2
·H2O
N
CHO
+
N
COAr
N
CH3
OHC
Ar
10 Steps
[4c]
Ar = Ph, 4-CH3C6H4
: CO2Me, Ph or H
and
H3C
N
CHO
Reaction conditions: PPInCl-nSiO2 (1.8 mol%), 110 °C, Solvent-Free
Recently, we reported propylphosphonium hydrogen carbonate ionic liquid supported on nano-silica
(PPHC-nSiO2) for the synthesis of various fully substituted pyridines.6 In the present study, after some
preliminary experiments upon the effect of catalyst on the yield of quinolines, the propylphosphonium
tetrachloroindate ionic liquid supported on nano-silica (PPInCl-nSiO2, Figure 1) was prepared and
selected as catalyst for quinoline synthesis (for more details, see the Experimental section and
Supporting information). The indium content of PPInCl-nSiO2 is 0.725 mmol per gram of the catalyst as
determined by ICP analysis.
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Figure 1. The schematic structure of PPInCl-nSiO2 along with its TEM image
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The reaction conditions of 2-amino-5-chlorobenzophenone 1b and dimethyl acetylenedicarboxylate
(DMAD, 2a) was investigated in point of molar ratios of substrates, the amount of catalyst and
temperature. The optimized conditions to give the highest yield of the desired quinoline was found to
be; 1:1.3 molar ratio of 1b:2a, 1.8 mol% PPInCl-nSiO2 (25 mg of catalyst) at 110 °C under solvent-free
conditions (Table 1, entry 7).
Table 1: Optimization of reaction conditions
Entry Catalyst 1b:2a
(mol%)a (eq:eq)b
T
Time
(h)
0.5
0.5
2
2
2
2
0.5
2
Yield
(%)c
99
99
76
70
67
86
99
(°C)
110
110
110
110
110
110
110
80
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2
3
4
5
6
7
8
9
10
3.6
1.8
1.0
3.6
1.8
1.8
1.8
1.8
1.8
1.8
1:1.5
1:1.5
1:1.5
1:1
1:1
1:1.2
1:1.3
1:1.3
1:1.3
1:1.3
64
81
98
100
120
2
0.5
a Reaction of 2-amino-5-chlorobenzophenone 1b and DMAD 2a in
the presence of PPInCl-nSiO2, according to ICP analysis : 50 mg
(3.6 mol% In), 25 mg (1.8 mol% In) and 15 mg (1.0 mol% In). b 2-
Amino-5-chlorobenzophenone 1b : DMAD 2a. c Isolated yield.
The substrates scope of this protocol was then investigated using the optimized conditions. As shown
in Scheme 2, different 2-aminoaryl ketones were reacted with internal alkynes such as DMAD 2a or
diphenylacetylene 2b in the presence of PPInCl-nSiO2, to afford the desired 2,3,4-trisubstituted
quinolines (3aa-3ea and 3bb-3eb) in good to excellent yields (65-99%). Furthermore, the reaction of 2-
aminoaryl ketones with terminal alkynes including methyl propiolate 2c and phenylacetylene 2d was
performed under the same conditions in orther to find out the selectivity of this catalyst. When methyl
propiolate 2c were treated with 2-amino-5-chlorobenzophenone 1b and/or 2-amino-5-chloro-2ˊ-
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fluorobenzophenone 1d, good yields of the corresponding 3,4-disubstituted quinolines (3bc and 3dc)
were selectively obtained. On the contrary, the reaction of phenylacetylene 2d with 2-aminoaryl ketones
selectively gave the corresponding 2,4-disubstituted quinolines (3bd-3ed) in 50-95% yields. The
structures of 3dc and 3cd as representative compounds were confirmed by X-ray crystallographic
analysis (Figure 2, CCDC of 3dc: 1857298 and CCDC of 3cd: 1857297).
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Scheme 2. Reaction of 2-aminoaryl ketones and alkynes catalyzed by
PPInCl-nSiO2
R2
R2
X
X
PPInCl-nSiO2
(1.8 mol%)
R1
R1
O
+
110 °C,
Solvent-Free
Y
NH2
N
Y
2a-d
3
1a-e
R2
Ph
R2
R1
R1
CO2Me
N
Ph
N
CO2Me
2a: X = Y = CO2Me
2b: X = Y = Ph
, R1 = H, R2 = H, 98% (20 min)
3aa
3ba
3ca
3da
3ea
, R1 = Cl, R2 = H, 67% (1 h)
, R1 = Cl, R2 = Cl, 72% (1 h)
, R1 = NO2, R2 = H, 65% (1 h)
3bb
3cb
3eb
, R1 = Cl, R2 = H, 99% (30 min)
, R1 = Cl, R2 = Cl, 88% (20 min)
, R1 = Cl, R2 = F, 98% (20 min)
, R1 = NO2, R2 = H, 75% (25 min)
R2
R2
R1
CO2Me
R1
N
N
Ph
2c: X = CO2Me, Y = H
2d: X = H, Y = Ph
, R1 = Cl, R2 = H, 87% (45 min)
, R1 = Cl, R2 = Cl, 98% (35 min)
, R1 = Cl, R2 = F, 95% (35 min)
, R1 = NO2, R2 = H, 50% (1 h)
, R1 = Cl, R2 = H, 79% (1 h)
, R1 = Cl, R2 = F, 66% (1 h)
3bd
3cd
3dd
3ed
3bc
3dc
(a)
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(b)
Figure 2. Molecular structures of 3dc (a) and 3cd (b), showing 40% probability displacement ellipsoids
and the atomic numbering
The synthesis of quinolines was also examined with substrates containing two 2-aminoaryl ketone
units such as 4,6-dibenzoyl-1,3-phenylenediamine 1f, 2,5-dibenzoyl-1,4-phenylenediamine 1g and 2,5-
ditolyl-1,4-phenylendiamine 1h. As shown in Scheme 3, when compounds 1f-h were reacted with
alkynes 2a-d in 1:1.3 molar ratios, only one of the 2-aminoaryl ketone groups took part selectively to
afford the respected quinolines in high yields. Importantly, the remaining 2-aminoaryl ketone group on
the quinoline backbone can be transformed to some other useful functional groups.
Another exceptional aspect of this catalytic system lies in the preparation of various pyrido[3,2-
g]quinolines and pyrido[2,3-g]quinolines. As evident from Scheme 4, treatment of 4,6-dibenzoyl-1,3-
phenylenediamine 1f (1 mmol) and alkynes 2a, 2b (2.6 mmol) in the presence of PPInCl-nSiO2 at 110
°C provided the related pyrido[3,2-g]quinolines in high yields within 10-12 h.
Scheme 3. Selective synthesis of quinolines containing 2-aminoaryl ketone group
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Ph
Ph
Ph
Ph
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2
3
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5
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7
8
X
Y
O
O
O
X
PPInCl-nSiO2
(1.8 mol%)
H2N
Ar
NH2
H2N
N
1f
or
+
or
Ar
110 °C,
Solvent-Free H2N
X
Y
NH2
O
O
2a-d
(1.3 mmol)
O
N
Y
H2N
Ar
Ar
1g
1h
, Ar = Ph
3
9
, Ar = 4-CH3C6H4
(1 mmol)
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2b: X = Y = Ph
Ph
2a: X = Y = CO2Me
Ar
2b: X = Y = Ph
Ph Ph
H2N
O
CO2Me
H2N
Ph
Ph
Ph
Ph
O
O
N
CO2Me
N
H2N
N
Ar
Ph
3gb
(68%, 1 h)
3fb
(64%, 3 h)
3ga
3ha
(96%, 15 min)
(92%, 1 h)
2d: X = H, Y = Ph
Ar
2c: X = CO2Me, Y = H
Ph
H2N
H
H2N
CO2Me
O
O
N
Ph
N
H
Ar
3gd
3hd
(83%, 1 h)
(71%, 1 h)
Ph 3gc
(95%, 4 h)
Scheme 4. Preparation of pyrido[3,2-g] quinolines
Ph
N
Ph
N
Ph
Ph
X
PPInCl-nSiO2
(1.8 mol%)
X
X
X
X
O
O
+
110 °C,
Solvent-Free
NH2
H2N
X
2a, b
1f
4
(1 mmol)
(2.6 mmol)
2b: X = Ph
Ph
2a: X = CO2Me
Ph
Ph
Ph
MeO2C
MeO2C
CO2Me Ph
CO2Me Ph
Ph
Ph
N
N
N
N
4fa
(76%, 10 h)
4fb
(68%, 12 h)
Similarly, the reaction of 2,5-diaroyl-1,4-phenylenediamines (1g and 1h, 1 mmol) with alkynes 2a-d
(2.6 mmol) under the optimized conditions led to a variety of symmetric pyrido[2,3-g]quinolines in high
yields (Scheme 5).
Scheme 5. Synthesis of symmetric pyrido[2,3-g]quinolines
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Ar
Ar
X
PPInCl-nSiO2
(1.8 mol%)
110 °C,
1
2
3
4
X
Y
N
Y
X
NH2
O
O
+
N
H2N
Solvent-Free
Y
Ar
Ar
5
1g
1h
, Ar = Ph
, Ar = 4-CH3C6H4
2a-d
5
6
(2.6 mmol)
(1 mmol)
7
2b: X = Y = Ph
Ph
2a: X = Y = CO Me
Ph
2
8
9
MeO2C
MeO2C
N
CO2Me Ph
N
Ph
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N
CO2Me Ph
N
Ph
Ph
Ph
5ga
(86%, 10 h)
5gb
(76%, 12 h)
2d: X = H, Y = Ph
Ar
2c: X = CO2Me, Y = H
Ar
H
N
Ph
H
MeO2C
H
N
H
Ph
N
N
CO2Me
Ar
Ar
5gc
5hc
(83%,10 h)
(71%, 12 h)
5hd
(80%,12 h)
Encouraged by the above mentioned promising results, we turned our attention to the one-pot, three-
component reaction of 2,5-dibenzoyl-1,4-phenylenediamine 1g (1 mmol) with two different alkynes,
DMAD 2a (1.3 mmol) and diphenylacetylene 2b (1.3 mmol). Interestingly, the corresponding
unsymmetric pyrido[2,3-g]quinoline 6gab was obtained in 81% yield (Scheme 6). It is worth
mentioning that the synthesis of quinolines and pyrido[3,2-g or 2,3-g]quinolines (Schemes 3-6) from
diaroylphenylenediamines 1f-h is reported for the first time which clearly indicates the novelty and
applicability of this catalytic method and makes this protocol very useful and effective for the
preparation of these vital heterocyclic compounds. Another outstanding feature of this method is that
such complex molecules are prepared via a single step.
Scheme 6. Synthesis of unsymmetric pyrido[2,3-g]quinoline
Ph
N
Ph
Ph
CO2Me
+
PPInCl-nSiO2
(1.8 mol%)
MeO2C
MeO2C
N
Ph
Ph
NH2
O
O
+
110 °C,
H2N
Solvent-Free
Ph
CO2Me
Ph
Ph
2b
2a
1g
(1 mmol)
6gab
(81%, 12 h)
(1.3 mmol)
(1.3 mmol)
As reported in the literature, tetrachloroindate(III) ionic liquid has been used as a Lewis acidic catalyst. 7
Accordingly, a plausible mechanism for the selective synthesis of 3,4- and 2,4-disubstituted quinolines
in the presence of PPInCl-nSiO2 is proposed in Scheme S1. First, the amino group of 2-aminoaryl
ketone 1 attacks the terminal carbon of methyl propiolate 2c in the presence of the catalyst to give
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intermediate A, in which the negative charge is stabilized by the carbonyl group of the ester. Then, A is
converted to β-enamino ester B by a prototropic shift from nitrogen to carbon. Finally, intramolecular
nucleophilic addition of carbon of β-enamino ester to the activated carbonyl group affords
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2
3
4
5
6
7
8
9
intermediate C, which upon dehydration in the presence of the catalyst results in the desired 3,4-
disubstituted quinoline selectively. For selective formation of 2,4-disubstituted quinoline, on the
basis of observed regiochemistry confirmed by X-ray analysis of 3cd, it is reasonable to assume that
nucleophilic addition of phenylacetylene to the activated carbonyl group of 2-aminoaryl ketone 1 gives
intermediate D, in which prototropic shift from carbon to oxygen affords propargylic alcohol E.
Next, the alcohol is transformed to the corresponding enone G by Meyer-Schuster rearrangement (via
the intermediate allenol F),8 which upon cyclization and subsequent dehydration in the presence of the
catalyst gives the related 2,4-disubstituted quinoline selectively.
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The reusability of PPInCl-nSiO2 which is very important from environmental and economical points
of view, was examined in the synthesis of 3ba. Upon reaction completion, the mixture was diluted with
EtOAc and the catalyst was separated, dried and then reused for subsequent reactions. The catalyst
could be reused at least 5 times without a significant loss of its activity (Table 2).
Table 2: Reusability of PPInCl-nSiO2 in the synthesis of 3ba
Entry a
1
2
3
4
5
6
Yield (%)b 99 99 98 97 97 95
a
Reaction
conditions:
2-amino-5-
chlorobenzophenone (1b, 1 mmol), DMAD (2a, 1.3
mmol) and PPInCl-nSiO2 catalyst (1.8 mol%), 110
°C. b Isolated yield.
To sum up, we presented a new catalytic strategy for the efficient synthesis of quinolines via the
reaction of various 2-aminoaryl ketones with terminal and internal alkynes in the presence of
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heterogeneous propylphosphonium tetrachloroindate ionic liquid supported on nano-silica catalyst
(PPInCl-nSiO2) under solvent-free conditions. Selective synthesis of novel quinolines containing one 2-
amino arylketone group was also carried out using this catalytic system. Also, for the first time, a
variety of symmetric and unsymmetric pyrido[3,2-g]quinolines and pyrido[2,3-g]quinolines were
prepared by the reaction of diaroylphenylenediamines with one alkyne or two different alkynes.
Notably, the PPInCl-nSiO2 catalyst could be recovered and reused several times by preserving its
activity.
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EXPERIMENTAL SECTION
General information
The chemicals used in this work were purchased from Fluka and Merck chemical companies. The
substrates containing two 2-aminoaryl ketone units 1f-h were prepared according to reported method.9
Melting points were determined with a Stuart Scientific SMP2 apparatus. FT-IR spectra were recorded
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on a Nicolet-Impact 400D spectrophotometer. H and 13C NMR (400 and 100 MHz) spectra were
recorded on a Bruker Avance 400 MHz spectrometer using CDCl3 solvent. The UV–vis diffuse
reflectance spectra of the samples were recorded on a JASCO V-670 spectrophotometer. Elemental
analysis was performed on a LECO, CHNS-932 analyzer. Thermogravimetric analysis (TGA) was
carried out on a Perkin-Elmer STA 6000 instrument under argon flow at a uniform heating rate of 20 °C
min-1 in the range 30-600 °C. The scanning electron microscope (SEM) measurement was carried out on
a Hitachi S-4700 field emission-scanning electron microscope. The transmission electron microscopy
(TEM) was carried out on a Philips CM10 instrument operating at 100 kV. The indium content of the
catalyst was determined by a Jarrell-Ash 1100 ICP analyzer.
Preparation and characterization of propylphosphonium tetrachloroindate ionic liquid
supported on nano-silica (PPInCl-nSiO2)
First, a mixture of 3 mL 3-chloropropyltrimethoxysilane (CPTMS) and nano-SiO2 (2 g) in 25 mL
anhydrous toluene was refluxed for 24 h. The reaction mixture was cooled to room temperature and
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filtered. The solid material was washed with toluene (40 mL) and a mixture of water-ethanol (40 mL,
1:1) to give chloropropylated nano-silica (CP-nSiO2). Then, a mixture of CP-nSiO2 (2 g) and
triphenylphosphine (8 g) in anhydrous toluene (25 mL) was refluxed under N2 atmosphere for 24 h.
After cooling to room temperature, the mixture was filtered and the solid material was washed with
toluene (40 mL) and ethanol (20 mL) to afford propylphosphonium chloride supported on nano-silica
(PPCl-nSiO2). Finally, a mixture of PPCl-nSiO2 (0.5 g) and indium chloride (0.442 g, 2 mmol) in
toluene (10 mL) was stirred vigorously at 50 °C under N2 atmosphere for 12 h. The mixture was
filtrated and the solid material was washed with toluene (20 mL) and then dried under vacuum at 70 °C
to afford propylphosphonium tetrachloroindate ionic liquid supported on nano-silica (PPInCl-nSiO2,
Supporting information, Figure S1). The prepared nanocatalyst was characterized by FT-IR, diffuse
reflectance UV–vis spectroscopy, TGA/DTG, SEM, TEM, and ICP. FT-IR spectra of nano-silica
(nSiO2) and propylphosphonium tetrachloroindate ionic liquid supported on nano-silica (PPInCl-nSiO2)
are presented in Figure S2. The characteristic bands at 3060 (sp2 C–H), 2931 and 1438 (C–H stretching
of the alkyl chain), 1101, 807 and 468 (Si–O), 1620 (C=C), 1482 and 789 cm-1 (P–C) were detected
which indicate the desired catalyst (PPInCl-nSiO2) has been prepared. The diffuse reflectance UV–vis
spectra of nSiO2, PPCl–nSiO2 and PPInCl-nSiO2 are shown in Figure S3. No absorption peak was
observed for nano-silica in the UV–vis spectrum. But PPCl-nSiO2 showed two significant absorption
peaks at 228 nm corresponds to π→π* transition of C=C phenyl groups and at 271 nm related to n→π*
lone electron pair in P-Ph.10 The same absorption peaks at 230 and 271 nm were detected for PPInCl-
nSiO2 catalyst. Also, a new absorption peak was observed at 196 nm which is related to a d-d transition
of indium.11 The TGA/DTG curves for PPInCl-nSiO2 catalyst was shown in Figure S4. The observed
total weight loss is 44.35%. The first step loss relates to removal of the physically adsorbed water (100-
130 °C, 3.03 %), whereas, the main weight loss corresponds to removal of the organic moieties from the
surface (350-600 °C, 41.32%). As indicated, the decomposition occurred in the range of 350-600 °C.
This high thermal stability provides good activity of the catalyst without any considerable leaching of
the active species at high temperature reaction. The morphology of the nano-SiO2 and PPInCl-nSiO2
catalysts was investigated by scanning electron microscopy (Figure S5). The morphology of the catalyst
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is different from that of nano-SiO2, indicating IL has been immobilized on the nanoparticles. The energy
dispersive X-ray (EDX) results, obtained from SEM analysis of PPInCl-nSiO2, is shown in Figure S6.
The presence of all the expected elements C, O, Si, Cl, P and In, indicates that the catalyst (PPInCl-
nSiO2) has been prepared. The size and morphology of the PPInCl-nSiO2 catalyst was also investigated
by transmission electron microscopy (TEM, Figure S7). The dark colored regions or black spots in the
photograph correspond to the indium species, while the colorless parts are related to nano-silica
particles.12 The histogram of size distribution showed that the particles diameter are in the range of 18-
26 nm (Figure S8).
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Investigation of the effect of catalyst for the synthesis of quinoline: In order to demonstrate the
usefulness of the catalyst, the reaction of 2-amino-5-chlorobenzophenone 1b and
dimethylacetylenedicarboxylate (DMAD, 2a) was performed in the absence of the catalyst at 110 °C; no
desired product was obtained under this conditions even after 10 h (Table S1). Then, the reaction was
performed in the presence of different catalysts such as H3PW12O40, p-TSA, BiCl3, FeCl3, ZnCl2, AlCl3,
nano-silica, propylphosphonium hydrogen carbonate ionic liquid supported on nano-silica (PPHC-
nSiO2),6 propylphosphonium tetrachloroindate ionic liquid supported on nano-silica (PPInCl-nSiO2).
The results listed in Table S1, clearly indicate that PPInCl-nSiO2 is the best catalyst for this
transformation. In order to show the advantages of supporting of IL on nanoparticles and also to
examine the effect of particle size on the activity of the catalyst, the model reaction was also performed
in the presence of InCl3 and homogenous butylphosphonium tetrachloroindate ([BuP]InCl4). Under
these conditions the desired product was obtained in 60% and 71% for InCl3 and [BuP]InCl4,
respectively, which are considerably lower than the yield obtained with PPInCl-nSiO2. These results
clearly showed that the supporting of IL on nano-silica leads to isolation of the active sites and
therefore, the activity of the catalyst is improved compared to the bulk InCl3 and butylphosphonium
tetrachloroindate.
Synthesis of quinoline derivatives catalyzed by PPInCl-nSiO2 (Scheme 2): A mixture of 2-
aminoaryl ketone (1 mmol), alkyne (1.3 mmol), and PPInCl-nSiO2 catalyst (25 mg, containing 0.018
o
mmol In, 1.8 mol%) was stirred at 110 C under solvent-free conditions. The progress of the reaction
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was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature
and then EtOAc (10 mL) was added. The catalyst was separated by filtration and washed with EtOAc
(10 mL). The filtrate was evaporated and the crude product was purified by recrystallization from EtOH
or silica gel column chromatography to afford the pure product.
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Dimethyl4-phenylquinoline-2,3-dicarboxylate (3aa): Purified by recrystallization from EtOH. Yield:
98% (314.60 mg). M.p = 124-126 °C (124-125 °C)13. FT-IR (KBr): νmax = 3446, 3064, 2993, 2951,
2924, 2853, 1739, 1616, 1561, 1484, 1447, 1370, 1305, 1244, 1204, 1100, 1049, 975, 849, 757 cm-1. 1H
NMR (400 MHz, CDCl3): δ = 3.67 (s, 3H), 4.10 (s, 3H), 7.38-7.40 (m, 2H), 7.52-7.54 (m, 3H), 7.62-
7.68 (m, 2H), 7.83-7.88 (m, 1H), 8.35 (d, J = 8.8 Hz, 1H).
Dimethyl 6-chloro-4-phenylquinoline-2,3-dicarboxylate (3ba): Purified by recrystallization from
EtOH. Yield: 99% (349.71 mg). M.p = 160-162 °C (164-165 °C)13. FT-IR (KBr): νmax = 3426, 3049,
2952, 2923, 1907, 1742, 1722, 1604, 1558, 1480, 1446, 1395, 1366, 1294, 1240 cm-1. 1H NMR (400
MHz, CDCl3): δ = 3.66 (s, 3H), 4.09 (s, 3H), 7.36-7.38 (m, 2H), 7.55-7.56 (m, 3H), 7.62 (d, J = 2.0 Hz,
1H), 7.77 (dd, 1J = 6.8 Hz, 2J = 2.4 Hz, 1H), 8.28 (d, J = 9.2 Hz, 1H).
Dimethyl 6-chloro-4-(2-chlorophenyl)quinoline-2,3-dicarboxylate (3ca): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 88% (342.12 mg). M.p = 188-190 °C
(190-192 °C)14. FT-IR (KBr): νmax = 3431, 3065, 2923, 2962, 2662, 1787, 1729, 1557, 1470, 1439,
1396, 1365, 1318, 1300, 1242, 1222, 1129, 1062 cm-1. 1H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3H),
4.07 (s, 3H), 7.26 (s, 1H), 7.28-7.32 (m, 2H), 7.49 (t, J = 2.0 Hz, 1H), 7.53-7.57 (m, 1H), 7.77 (dd, 1J =
6.8 Hz, 2J = 2.4 Hz, 1H), 8.27 (d, J = 9.2 Hz, 1H).
Dimethyl 6-chloro-4-(2-fluorophenyl)quinoline-2,3-dicarboxylate (3da): Purified by recrystallization
from EtOH. Yield: 98% (365.07 mg). M.p = 199-201 °C. FT-IR (KBr): νmax = 3427, 3077, 2954, 2850,
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1728, 1665, 1612, 1559, 1480, 1442, 1399, 1303, 1247, 1224, 1146, 1104, 1053, 957, 835 cm-1. H
NMR (400 MHz, CDCl3): δ = 3.66 (s, 3H), 4.09 (s, 3H), 7.28 (dd, 1J = 6.0 Hz, 2J = 1.6 Hz, 1H), 7.39 (d,
J = 2.0 Hz, 1H), 7.43 (td, 1J = 6.4 Hz, 2J = 1.2 Hz, 1H), 7.49 (td, 1J = 6.4 Hz, 2J = 1.6 Hz, 1H), 7.59 (dd,
1J = 6.8 Hz, 2J = 1.2 Hz, 1H), 7.78 (dd, 1J = 6.8 Hz, 2J = 2 Hz, 1H), 8.30 (d, J =9.2 Hz, 1H). 13C NMR
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(100 MHz, CDCl3): δ = 166.3, 164.7, 160.2 (d, 1JCF = 240 Hz), 145.1, 144.8, 141.3, 135.5, 131.9, 131.8,
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131.2, 131.1, 130.7, 130.6, 127.9, 127.7, 124.5, 123.9, 123.8, 121.1, 120.9, 115.6 (d, JCF = 20 Hz),
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53.1, 52.2. Anal. Calcd for C19H13ClFNO4: C, 61.06; H, 3.51; N, 3.75. Found: C, 61.19; H, 3.55; N,
3.68.
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Dimethyl 6-nitro-4-phenylquinoline-2,3-dicarboxylate (3ea): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 75% (273.24 mg). M.p = 190-192 °C. FT-
IR (KBr): νmax = 3440, 3097, 2955, 2924, 2853, 1917, 1746, 1728, 1620, 1575, 1535, 1482, 1438, 1370,
1347, 1218, 1151, 1088, 1051 cm-1. 1H NMR (400 MHz, CDCl3): δ = 3.69 (s, 3H), 4.12 (s, 3H), 7.39-
7.41 (m, 2H), 7.59-7.61 (m, 3H), 8.49-8.51 (m, 1H), 8.59-8.61 (m, 2H). 13C NMR (100 MHz, CDCl3): δ
= 166.2, 164.4, 149.9, 148.4, 147.7, 146.8, 132.5, 132.0, 129.3, 128.7, 128.3, 128.1, 126.5, 123.9, 122.9,
53.3, 52.3. Anal. Calcd for C19H14N2O6: C, 62.30; H, 3.85; N, 7.65. Found: C, 62.40; H, 3.80; N, 7.58.
6-Chloro-2,3,4-triphenylquinoline (3bb): Purified by silica gel column chromatography (eluent:
petroleum ether/EtOAc, 4:1). Yield: 67% (260.34 mg). M.p = 191-193 °C ( 193-194 °C)3a. FT-IR
(KBr): νmax = 3426, 3059, 3021, 2959, 2923, 1802, 1730, 1603, 1543, 1468, 1443, 1367, 1344, 1287,
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1122, 1075, 1024, 699 cm-1. H NMR (400 MHz, CDCl3): δ = 6.86-6.89 (m, 2H), 7.00-7.02 (m, 2H),
7.11-7.13 (m, 2H), 7.21-7.22 (m, 2H), 7.25-7.26 (m, 1H), 7.28-7.30 (m, 3H), 7.35-7.37 (m, 2H), 7.54-
7.55 (m, 1H), 7.65-7.74 (m, 2H), 8.17-8.20 (m, 1H).
6-Chloro-4-(2-chlorophenyl)-2,3-diphenylquinoline (3cb): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 72% (304.50 mg). M.p = 184-186 °C. FT-
IR (KBr): νmax = 3423, 3058, 2921, 2654, 1725, 1607, 1588, 1468, 1440, 1343, 1263, 1223, 1153, 1111,
1078, 1030, 929, 756, 700 cm-1. 1H NMR (400 MHz, CDCl3): δ = 6.86-6.87 (m, 1H), 7.03-7.04 (m, 4H),
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7.16-7.20 (m, 1H), 7.21-7.24 (m, 4H), 7.31 (d, J = 2.2 Hz, 1H), 7.38-7.41 (m, 4H), 7.66 (dd, J = 6.7
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Hz, J = 2.3 Hz, 1H), 8.19 (d, J = 8.9 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ = 159.4, 145.6, 144.4,
140.5, 137.7, 135.6, 134.2, 133.7, 132.8, 131.7, 131.5, 130.7, 130.5, 129.9, 129.5, 129.4, 127.9, 127.8,
127.3, 126.9, 126.8, 126.6, 124.8. Anal. Calcd for C27H17Cl2N: C, 76.06; H, 4.02; N, 3.29. Found: C,
76.19; H, 3.98; N, 3.21.
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6-Nitro-2,3,4-triphenylquinoline (3eb): Purified by silica gel column chromatography (eluent:
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petroleum ether/EtOAc, 2:1). Yield: 65% (259.98 mg). M.p = 179-181 °C. FT-IR (KBr): νmax = 3430,
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1074, 1027, 700 cm-1. 1H NMR (400 MHz, CDCl3): δ = 6.88 (dd, J = 5.8 Hz, J = 1.5 Hz, 2H), 7.04-
7.05 (m, 3H), 7.12-7.14 (m, 2H), 7.33-7.35 (m, 3H), 7.38 (dd,1J = 6.2 Hz, J = 1.4 Hz, 3H), 7.52-7.55
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(m, 1H), 7.74 (d, J = 7.2 Hz, 1H), 8.35 (d, J = 9.2 Hz, 1H), 8.48 (dd, 1J = 6.7 Hz, 2J = 2.5 Hz, 1H), 8.55
(d, J = 2.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ = 162.5, 149.7, 149.4, 145.6, 140.3, 137.3, 135.4,
134.8, 131.5, 131.1, 130.1, 129.9, 128.4, 128.3, 128.2, 127.9, 127.7, 126.9, 125.9, 123.8, 122.9. Anal.
Calcd for C27H18N2O2: C, 85.58; H, 4.51; N, 6.96. Found: C, 85.73; H, 4.54; N, 7.03.
Methyl 6-chloro-4-phenylquinoline-3-carboxylate (3bc): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 79% (230.87 mg). yellow gummy mass13.
FT-IR (KBr): νmax = 3436, 3060, 2951, 2850, 1727, 1577, 1483, 1439, 1353, 1300, 1260, 1216, 1126,
1077, 840, 758 cm-1. 1H NMR (400 MHz, CDCl3): δ = 3.71 (s, 3H), 7.29-7.32 (m, 2H), 7.55-7.57 (m,
3H), 7.59 (d, J = 2.0 Hz, 1H), 7.75 (dd, 1J = 6.8 Hz, 2J = 2.0 Hz, 1H), 8.18 (d, J = 9.2 Hz, 1H), 9.35 (s,
1H).
Methyl 6-chloro-4-(2-fluorophenyl)quinoline-3-carboxylate (3dc): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 66% (205.68 mg). M.p = 164-166 °C. FT-
IR (KBr): νmax = 3432, 3028, 2959, 2924, 2853, 1726, 1616, 1575, 1483, 1443, 1355, 1286, 1214, 1125,
1102, 1074, 600 cm-1. 1H NMR (400 MHz, CDCl3): δ = 3.79 (s, 3H), 7.24-7.28 (m, 1H), 7.31-7.37 (m,
2H), 7.53-7.56 (m, 2H), 7.76 (dd, 1J = 6.6 Hz, 2J = 2.3 Hz, 1H), 8.16 (d, J = 9.0 Hz, 1H), 9.45 (s, 1H).
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13C NMR (100 MHz, CDCl3): δ = 169.1, 158.3, 149.9, 142.1 (d, JCF = 160 Hz), 131.8, 130.9, 130.4,
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130.3, 130.1, 130.0, 128.5, 127.7, 125.2, 123.7, 123.6, 115.3 (d, JCF = 22 Hz), 52.0. Anal. Calcd for
C17H11ClFNO2: C, 64.67; H, 3.51; N, 4.44. Found: C, 64.89; H, 3.48; N, 4.37.
6-Chloro-2,4-diphenylquinoline (3bd): Purified by silica gel column chromatography (eluent:
petroleum ether/EtOAc, 2:1). Yield: 87% (273.15 mg). M = 98-99 °C (98-99 °C)5a. FT-IR (KBr): νmax
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3431, 3056, 3028, 2927, 1896, 1588, 1538, 1480, 1443, 1355, 1240, 1146, 1074, 886, 823, 788, 700
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Cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.49-7.60 (m, 8H), 7.69 (dd, 1J = 6.6 Hz, 2J = 2.3 Hz, 1H), 7.87
(s, 1H), 7.89 (d, J = 2.3 Hz, 1H), 8.19-8.22 (m, 3H).
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6-Chloro-4-(2-chlorophenyl)-2-phenylquinoline (3cd): Purified by recrystallization from EtOH.
Yield: 98% (341.62 mg). M.p = 110-112 °C (112-114 °C)5a. FT-IR (KBr): νmax = 3429, 3344, 3214,
3056, 3025, 2920, 2660, 1598, 1585, 1542, 1470, 1435, 1353, 1227, 1156, 1128, 1053, 1029, 885, 829
cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.40 (dd, 1J = 5.4 Hz, 2J = 1.8 Hz, 1H), 7.46-7.58 (m, 6H), 7.62
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(dd, J = 6.3 Hz, J = 1.6 Hz, 1H), 7.69 (dd, J = 6.7 Hz, J = 2.3 Hz, 1H), 7.85 (s, 1H), 8.20 (s, 2H),
8.21-8.23 (m, 1H).
6-Chloro-4-(2-fluorophenyl)-2-phenylquinoline (3dd): Purified by recrystallization from EtOH. Yield:
95% (314.74 mg). M.p = 125-127 °C (124-126 °C)5a. FT-IR (KBr): νmax = 3426, 3059, 3032, 1615,
1588, 1542, 1479, 1447, 1360, 1352, 1256, 1232, 1207, 1073, 1025, 884, 753 cm-1. H NMR (400
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MHz, CDCl3): δ =7.40-7.49 (m, 2H), 7.54-7.67 (m, 5H), 7.76-7.80 (m, 2H), 7.98 (s, 1H), 8.29-8.31 (m,
3H).
6-Nitro-2,4-diphenylquinoline (3ed): Purified by silica gel column chromatography (eluent: petroleum
ether/EtOAc, 2:1). Yield: 50% (161.7 mg). M.p: 265-266 °C (265-266 °C)5a. FT-IR (KBr): νmax = 3414,
3067, 2958, 2924, 2855, 1729, 1647, 1462, 1381, 1339, 1282, 1122, 1078, 1041, 743, 700 cm-1. H
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NMR (400 MHz, CDCl3): δ =7.52-7.65 (m, 8H), 7.99 (s, 1H), 8.24 (dd, J = 6.4 Hz, J = 1.7 Hz, 2H),
8.33 (d, J = 9.2 Hz, 1H), 8.49 (dd, 1J = 6.7 Hz, 2J = 2.5 Hz, 1H), 8.86 (d, J = 2.4 Hz, 1H).
Synthesis of quinolines contains 2-aminoaryl ketone group catalyzed by PPInCl-nSiO2 (Scheme
3): The substrates containing two parts of 2-aminoaryl ketones [1f, 1g and 1h (1 mmol)],9 alkyne (1.3
o
mmol) and PPInCl-nSiO2 catalyst (25 mg, containing 0.018 mmol In, 1.8 mol%) was stirred at 110 C
under solvent-free conditions. The progress of the reaction was monitored by TLC. After completion of
the reaction, the mixture was cooled to room temperature and then EtOAc (10 mL) was added. The
catalyst was separated by filtration and washed with EtOAc (10 mL). The filtrate was evaporated and
the crude product was purified by silica gel column chromatography to afford the pure desired
quinolines.
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(7-Amino-2,3,4-triphenylquinoline-6-yl)(phenyl)methanone (3fb): Purified by silica gel column
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chromatography (eluent: petroleum ether/EtOAc, 1.5:1). Yield: 64% (301.30 mg). M.p = 99-100 °C.
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FT-IR (KBr): νmax = 3429, 3067, 2957, 2926, 2857, 1730, 1642, 1458, 1879, 1282, 1123, 1072, 744,
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700, 465 cm-1. H NMR (400 MHz, CDCl3): δ = 5.80 (s, 2H), 6.76-6.78 (m, 2H), 6.90-6.92 (m, 3H),
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6.93-6.96 (m, 2H), 7.02-7.04 (m, 3H), 7.13-7.15 (m, 3H), 7.28-7.31 (m, 5H), 7.36 (s, 1H), 7.54 (m, 2H),
7.69 (s, 1H). 13C NMR (100 MHz, CDCl3): δ = 198.5, 149.3, 141.0, 138.8, 138.2, 136.4, 135.9, 131.9,
131.5, 129.9, 129.8, 129.7, 129.6, 129.2, 128.2, 128.1, 127.9, 127.8, 127.7, 127.6, 127.4, 127.3, 126.2,
122.2, 118.7, 111.2. Anal. Calcd for C34H24N2O: C, 85.69; H, 5.08; N, 5.88. Found: C, 85.82; H, 5.11;
N, 5.78.
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Anal. Calcd for C34H24N2O: C, 85.69; H, 5.08; N, 5.88. Found: C, 85.82; H, 5.11; N, 5.78.
Dimethyl 6-amino-7-benzoyl-4-phenylquinoline-2,3-dicarboxylate (3ga): Purified by recrystallization
from EtOH. Yield: 96% (418.15 mg). M.p = 183-185 °C. FT-IR (KBr): νmax = 3474, 3370, 3056, 2948,
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2924, 2857, 1722, 1644, 1619, 1591, 1484, 1429, 1388, 1283, 1250, 1221, 1176 cm-1. H NMR (400
MHz, CDCl3): δ = 3.65 (s, 3H), 4.03 (s, 3H), 5.82 (s, 2H), 6.69 (s, 1H), 7.37-7.39 (m, 2H), 7.53-7.55
(m, 5H), 7.64 (t, J = 7.6 Hz, 1H), 7.77 (d, J = 7.2 Hz, 2H), 8.47 (s, 1H). 13C NMR (100 MHz, CDCl3): δ
=195.5, 171.1, 166.6, 142.5, 138.1, 136.8, 132.6, 129.8, 129.7, 129.4, 129.3, 129.2, 128.9, 128.6, 128.5,
127.3, 108.1, 53.4, 52.5. Anal. Calcd for C26H20N2O5: C, 70.90; H, 4.58; N, 6.36. Found: C, 71.04; H,
4.54; N, 6.28.
Dimethyl 6-amino-7-(4-methylbenzoyl)-4-(p-tolyl)quinoline-2,3-dicarboxylate (3ha): Purified by
recrystallization from EtOH. Yield: 92% (428.32 mg). M.p = 258-260 °C. FT-IR (KBr): νmax = 3453,
3355, 3056, 2922, 2854, 1744, 1714, 1617, 1486, 1439, 1391, 1299, 1247, 1214, 1183, 1053, 879 cm-1.
1H NMR (400 MHz, CDCl3): δ = 2.48 (s, 6H), 3.68 (s, 3H), 4.03 (s, 3H), 5.72 (s, 2H), 6.72 (s, 1H),
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7.26-7.29 (m, 1H), 7.31 (t, J = 7.4 Hz, 5H), 7.70 (d, J = 8.1 Hz, 2H), 8.44 (s, 1H). C NMR (100 MHz,
CDCl3): δ = 198.5, 165.6, 152.0, 148.5, 143.5, 139.9, 138.7, 137.6, 135.9, 133.6, 132.1, 131.4, 130.1,
129.3, 129.2, 127.7, 126.3, 108.1, 53.4, 52.5, 21.7, 21.4. Anal. Calcd for C28H24N2O5: C, 71.78; H, 5.16;
N, 5.98. Found: C, 71.91; H, 5.19; N, 5.89.
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(6-Amino-2,3,4-triphenylquinoline-7-yl)(phenyl) methanone (3gb): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 68% (320.78 mg). M.p = 268-270 °C. FT-
IR (KBr): νmax = 3470, 3350, 3057, 3026, 2954, 1721, 1637, 1609, 1581, 1525, 1478, 1448, 1411, 1317,
1246, 1202, 1177, 1068, 954, 750, 695 cm-1. 1H NMR (400 MHz, CDCl3): δ = 5.83 (s, 2H), 6.32 (s, 1H),
7.28 (s, 1H), 7.33-7.43 (m, 7H), 7.51-7.60 (m, 6H), 7.73-7.75 (m, 7H). 13C NMR (100 MHz, CDCl3): δ
= 198.5, 169.4, 146.9, 140.2, 139.5, 137.5, 134.2, 131.5, 131.2, 129.3, 129.1, 128.8, 128.4, 128.3, 127.7,
126.3, 119.4, 115.5. Anal. Calcd for C34H24N2O: C, 85.69; H, 5.08; N, 5.88. Found: C, 85.57; H, 5.05;
N, 5.97.
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Methyl 6-amino-7-benzoyl-4-phenylquinoline-2-carboxylate (3gc): Purified by recrystallization from
EtOH. Yield: 95% (359.14 mg). M.p = 190-193 °C. FT-IR (KBr): νmax = 3474, 3370, 3056, 2948, 2924,
2857, 1722, 1644, 1619, 1591, 1484, 1429, 1388, 1283, 1250, 1221, 1176 cm-1. 1H NMR (400 MHz,
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CDCl3): δ =3.69 (s, 3H), 5.58 (s, 2H), 6.71 (s, 1H), 7.30 (dd, J = 5.6 Hz, J = 1.6 Hz, 1H), 7.50-7.56
(m, 5H), 7.61-7.65 (m, 1H), 7.72-7.74 (m, 1H), 7.80 (d, J = 7.1 Hz, 2H), 8.31 (s, 1H), 9.04 (s, 1H). 13C
NMR (100 MHz, CDCl3): δ = 198.7, 166.9, 146.9, 146.88, 146.85, 136.4, 132.5, 131.2, 131.1, 130.9,
129.9, 129.3, 129.1, 128.8, 128.7, 128.5, 128.3, 128.2, 109.6, 52.3. Anal. Calcd for C24H18N2O3: C,
75.38; H, 4.74; N, 7.33. Found: C, 75.51; H, 4.70; N, 7.26.
(6-Amino-2,4-diphenylquinoline-7-yl)(phenyl) methanone (3gd): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 83% (330.25 mg). M.p = 261-263 °C. FT-
IR (KBr): νmax = 3467, 3344, 3313, 3197, 3057, 3028, 2921, 2851, 2250, 1722, 1609, 1577, 1526, 1445,
1412, 1318, 1244, 1205, 1177, 1069, 954, 883, 696 cm-1. 1H NMR (400 MHz, CDCl3): δ = 5.83 (s, 2H),
6.32 (s, 1H), 7.23 (s, 1H), 7.35 (t, J = 7.2 Hz, 3H), 7.40-7.43 (m, 2H), 7.50-7.54 (m, 4H), 7.57-7.60 (m,
2H), 7.73-7.75 (m, 5H). 13C NMR (100 MHz, CDCl3): δ = 198.5, 169.5, 147.0, 140.2, 139.5, 137.5,
134.2, 134.1, 133.6, 131.5, 131.2, 130.6, 130.3, 129.6, 129.3, 129.2, 129.1, 128.9, 128.3, 126.3, 119.4,
115.5. Anal. Calcd for C28H20N2O: C, 83.98; H, 5.03; N, 7.00. Found: C, 83.85; H, 4.99; N, 7.08.
(6-Amino-2-phenyl-4-(p-tolyl)quinoline-7-yl)(p-tolyl)methanone (3hd): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 71% (300.70 mg). M.p = 101-103 °C. FT-
IR (KBr): νmax = 3466, 3365, 3028, 2951, 2921, 2734, 2587, 1911, 1724, 1644, 1619, 1598, 1528, 1491,
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1451, 1356, 1289, 1213, 1179, 1072, 895, 769 cm-1. H NMR (400 MHz, CDCl3): δ = 2.40 (s, 3H), 2.42
(s, 3H), 5.42 (s, 2H), 7.01 (s, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 6.8 Hz, 2H), 7.36-7.43 (m, 5H),
7.65 (s, 1H), 7.68 (d, J = 8.1 Hz, 2H), 7.99-8.01 (m, 2H), 8.27 (s, 1H). 13C NMR (100 MHz, CDCl3): δ
= 198.2, 157.2, 151.6, 149.6, 144.7, 143.1, 140.6, 134.8, 132.9, 130.2, 130.0, 129.4, 129.3, 129.1, 128.8,
127.1, 124.3, 121.4, 119.8, 108.1, 21.3. Anal. Calcd for C30H24N2O: C, 84.08; H, 5.65; N, 6.54. Found:
C, 84.20; H, 5.61; N, 6.45.
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Synthesis of pyrido[3,2-g]quinolines catalyzed by PPInCl-nSiO2 (Scheme 4): A mixture of 4,6-
dibenzoyl-1,3-phenylenediamine (1f, 1 mmol), alkyne (2.6 mmol) and PPInCl-nSiO2 catalyst (50 mg,
containing 0.036 mmol In, 1.8 mol%) was stirred at 110 oC under solvent-free conditions. The progress
of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to
room temperature and then EtOAc (10 mL) was added. The catalyst was separated by filtration and
washed with EtOAc (10 mL). The filtrate was evaporated and the crude product was purified by silica
gel column chromatography to afford the pure desired pyrido[3,2-g]quinolines.
Tetramethyl 4,6-diphenylpyrido[3,2-g]quinoline-2,3,7,8-tetracarboxylate (4fa): Purified by silica gel
column chromatography (eluent: petroleum ether/EtOAc, 1.5:1). Yield: 76% (421.56 mg). M.p = 124-
126 °C. FT-IR (KBr): νmax = 3442, 3330, 2959, 2925, 2856, 2741, 1729, 1602, 1440, 1377, 1262, 1123,
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1070, 997, 744 cm-1. H NMR (400 MHz, CDCl3): δ =3.91 (s, 6H), 3.97 (s, 6H), 7.55-7.72 (m, 6H),
7.73-7.79(m, 5H), 8.70 (s, 1H). 13C NMR (100 MHz, CDCl3): δ = 168.3, 164.4, 139.2, 134.3, 132.6,
130.9, 130.0, 129.5, 129.3, 128.8, 128.7, 128.2, 53.3, 53.2. Anal. Calcd for C32H24N2O8: C, 68.08; H,
4.29; N, 4.96. Found: C, 68.21; H, 4.33; N, 4.88.
2,3,4,6,7,8-Hexaphenylpyrido[3,2-g]quinoline (4fb): Purified by silica gel column chromatography
(eluent: petroleum ether/EtOAc, 2:1). Yield: 68% (429.38 mg). M.p = 143-145 °C. FT-IR (KBr): νmax
=
3467, 3306, 3055, 3028, 2959, 2923, 2853, 1952, 1725, 1688, 1593, 1553, 1445, 1490, 1377, 1282,
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1119, 1072, 1025, 761, 698 cm-1. H NMR (400 MHz, CDCl3): δ = 6.84-6.86 (m, 2H), 6.90-6.95 (m,
7H), 7.03-7.05 (m, 3H), 7.07-7.09 (m, 1H), 7.12-7.16 (m, 2H), 7.17-7.19 (m, 3H), 7.23-7.29 (m, 4H),
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7.30-7.34 (m, 2H), 7.38-7.40 (m, 3H), 7.42-7.48 (m, 3H), 7.69-7.75 (m, 2H). C NMR (100 MHz,
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CDCl3): δ = 161.1, 131.4, 130.8, 130.1, 130.0, 129.9, 129.4, 128.5. 128.3, 127.9, 127.7, 127.6, 127.4,
127.1. Anal. Calcd for C48H32N2: C, 90.54; H, 5.07; N, 4.40. Found: C, 90.40; H, 5.04; N, 4.47
Synthesis of symmetric pyrido[2,3-g]quinolines catalyzed by PPInCl-nSiO2 (Scheme 5): A
mixture of 2,5-dibenzoyl-1,4-phenylenediamine 1g / or 2,5-ditolyl-1,4-phenylendiamine 1h (1 mmol),
alkyne (2.6 mmol) and PPInCl-nSiO2 catalyst (50 mg, containing 0.036 mmol In, 1.8 mol%) was stirred
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at 110 C under solvent-free condition. The progress of the reaction was monitored by TLC. After
completion of the reaction, the mixture was cooled to room temperature and then EtOAc (10 mL) was
added. The catalyst was separated by filtration and washed with EtOAc (10 mL). The filtrate was
evaporated and the crude product was purified by silica gel column chromatography to afford the pure
desired symmetric pyrido[2,3-g]quinolines.
Tetramethyl 4,9-diphenylpyrido[2,3-g]quinoline-2,3,7,8-tetracarboxylate (5ga): Purified by silica gel
column chromatography (eluent: petroleum ether/EtOAc, 1.5:1). Yield: 86% (482.45 mg). M.p >300 °C.
FT-IR (KBr): νmax = 3431, 3060, 2951, 2924, 2854, 1734, 1654, 1570, 1525, 1442, 1353, 1259, 1216,
1146, 1111, 974, 700, 469 cm-1. 1H NMR (400 MHz, CDCl3): δ =3.58 (s, 6H), 3.99 (s, 6H), 7.35-7.37
(m, 5H), 7.47-7.50 (m, 5H), 8.72 (s, 2H). 13C NMR (100 MHz, CDCl3): δ = 165.3, 164.2, 157.0, 150.9,
144.3, 133.8, 130.3, 129.9, 129.4, 129.3, 128.8, 128.7, 53.8, 52.7. Anal. Calcd for C32H24N2O8: C,
68.08; H, 4.29; N, 4.96. Found: C, 67.92; H, 4.25; N, 5.04.
2,3,4,7,8,9-Hexaphenylpyrido[2,3-g]quinoline (5gb): Purified by silica gel column chromatography
(eluent: petroleum ether/EtOAc, 2:1). Yield: 76% (480.12 mg). M.p= 288-290 °C. FT-IR (KBr): νmax
=
3427, 3056, 3026, 2922, 2850, 1952, 1725, 1619, 1574, 1464, 1441, 1315, 1260, 1150, 1075, 1025, 764
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cm-1. H NMR (400 MHz, CDCl3): δ = 6.72-6.80 (m, 3H), 6.91-6.97 (m, 5H), 7.08-7.11 (m, 6H), 7.17
(s, 2H), 7.21-7.28 (m, 9H), 7.31-7.42 (m, 3H), 7.73-7.75 (m, 2H), 7.81 (s, 1H), 7.83-7.85 (m, 1H). 13C
NMR (100 MHz, CDCl3): δ = 169.8, 147.1, 138.1, 137.5, 136.5, 131.5, 131.2, 130.3, 130.2, 129.8,
129.5, 128.9, 128.3, 128.1, 127.9, 127.7, 127.4, 126.4, 116.4. Anal. Calcd for C48H32N2: C, 90.54; H,
5.07; N, 4.40. Found: C, 90.51; H, 5.11; N, 4.30.
Dimethyl 4,9-diphenylpyrido[2,3-g]quinoline-2,7-dicarboxylate (5gc): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 83% (368.54 mg). M.p = 157-160 °C. FT-
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IR (KBr): νmax = 3445, 3049, 2955, 2926, 2856, 1731, 1595, 1538, 1491, 1438, 1348, 1282, 1212, 1121,
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(m, 8H), 8.61 (s, 1H), 9.40 (s, 1H). 13C NMR (100 MHz, CDCl3): δ = 171.2, 168.8, 162.4, 151.6, 130.9,
129.5, 128.8, 128.77, 128.73, 128.5, 116.4 52.5. Anal. Calcd for C28H20N2O4: C, 74.99; H, 4.50; N,
6.25. Found: C, 75.15; H, 4.53; N, 6.17.
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Dimethyl 4,9-di-p-tolylpyrido[2,3-g]quinoline-3,8-dicarboxylate (5hc): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 71% (332.90 mg). M.p = 235-237 °C. FT-
IR (KBr): νmax = 3466, 3365, 3028, 2951, 2921, 2734, 2587, 1911, 1724, 1644, 1619, 1598, 1528, 1491,
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1451, 1356, 1289, 1213, 1072, 895, 769 cm-1. H NMR (400 MHz, CDCl3): δ = 2.43 (s, 6H), 3.62 (s,
3H), 3.99 (s, 3H), 7.23-7.31 (m, 8H), 7.45-7.48 (m, 2H), 7.63-7.65 (m, 1H), 8.72 (s, 1H). 13C NMR (100
MHz, CDCl3): δ = 165.4, 149.5, 144.3, 139.4, 130.9, 130.8, 130.3, 129.4, 129.2, 129.1, 128.8, 128.6,
53.8, 52.7, 23.7, 23.0. Anal. Calcd for C30H24N2O4: C, 75.62; H, 5.08; N, 5.88. Found: C, 75.48; H,
5.12; N, 5.95.
3,8-Diphenyl-4,9-di-p-tolylpyrido[2,3-g]quinoline (5hd): Purified by silica gel column
chromatography (eluent: petroleum ether/EtOAc, 2:1).Yield: 80% (408.65 mg). M.p >300 °C. FT-IR
(KBr): νmax = 3427, 2948, 2924, 2867, 2734, 1737, 1609, 1500, 1445, 1360, 1252, 1219, 1114, 1048,
788 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.46 (s, 6H), 7.35 (d, J = 7.8 Hz, 4H), 7.41-7.48 (m, 7H),
7.53 (d, J = 7.9 Hz, 4H), 7.79 (s, 2H), 8.14 (d, J = 7.1 Hz, 3H), 8.81 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ = 141.5, 130.0, 129.7, 129.6, 129.5, 129.4, 129.0, 128.9, 128.8, 127.7, 127.6, 127.2, 126.9,
119.6, 21.4. Anal. Calcd for C38H28N2: C, 89.03; H, 5.51; N, 5.46. Found: C, 89.17; H, 5.49; N, 5.27.
Synthesis of unsymmetric pyrido[2,3-g]quinolines catalyzed by PPInCl-nSiO2 (Scheme 6): A
three-component reaction of 2,5-dibenzoyl-1,4-phenylenediamine 1g (1 mmol) with DMAD 2a (1.3
mmol) and diphenyl acetylene 2b (1.3 mmol) in the presence of PPInCl-nSiO2 catalyst (50 mg,
containing 0.036 mmol In, 1.8 mol%) was stirred at 110 oC under solvent-free conditions. The progress
of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to
room temperature and then EtOAc (10 mL) was added. The catalyst was separated by filtration and
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washed with EtOAc (10 mL). The filtrate was evaporated and the crude product was purified by silica
gel column chromatography to afford the pure desired unsymmetric pyrido[2,3-g]quinolines.
Dimethyl 4,7,8,9-tetraphenylpyrido[2,3-g]quinoline-2,3-dicarboxylate (6gab): Purified by silica gel
column chromatography (eluent: petroleum ether/EtOAc, 2:1). Yield: 81% (484.35 mg). M.p>310 °C.
FT-IR (KBr): νmax = 3439, 3060, 2955, 2924, 2730, 1969, 1732, 1579, 1526, 1446, 1358, 1259, 1218,
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(m, 10H), 7.60-7.65 (m, 6H), 7.72-7.74 (m, 1H), 7.94 (s, 1H), 8.20 (dd, 1 J = 6.4 Hz, 2 J = 1.4 Hz, 2H),
8.64 (s, 1H), 9.01 (s, 1H). 13C NMR (100 MHz, CDCl3): δ = 174.5, 173.6, 150.7, 149.4, 131.4, 131.0,
130.3 129.6, 129.4, 129.0, 128.9, 128.8, 128.6, 128.3, 128.1, 127.8, 120.5, 118.3, 105.6, 53.7, 52.6.
Anal. Calcd for C40H28N2O4: C, 79.98; H, 4.70; N, 4.66. Found: C, 80.11; H, 4.66; N, 4.57.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications websiteat.
1
Detailed preparation and characterization of PPInCl-nSiO2 catalyst, proposed mechanism, copies of H
and 13C NMR spectra of the products and X-ray crystallographic data (PDF).
X-ray crystallographic data for compound 3cd (CIF)
X-ray crystallographic data for compound 3dc (CIF)
Accession Codes
CCDC 1857297 and 1857298 contain the supplementary crystallographic data for this paper.
AUTHOR INFORMATION
Corresponding Author
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* E-mail: imbaltork@sci.ui.ac.ir
Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENT
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We are grateful to the Iranian National Science Foundation (INSF) project number 95828022 and the
Research Council of the University of Isfahan for the financial support of this work.
REFERENCES
(1) For general review regarding the quinolines, see: (a) Manske, R. H. The Chemistry of Quinolines.
Chem. Rev. 1942, 30, 113. (b) Afzal, O.; Kumar, S.; Haider, M. R.; Ali, M. R.; Kumar, R.; Jaggi, M.;
Bawa, S. A review on anticancer potential of bioactive heterocycle quinoline. Eur. J. Med. Chem. 2015,
97, 871. (c) Marella, A.; Tanwar, O. P.; Saha, R.; Ali, M. R.; Srivastava, S.; Akhter, M.;
Shaquiquzzaman, M.; Alam, M. Quinoline: A versatile heterocyclic. Saudi Pharm. J. 2013, 21, 1. (d)
Gopaul, K.; Shintre, S. A.; Koorbanally, N. A. A Review on the Synthesis and Anti-cancer Activity of
2-substituted Quinolines. Anticancer Agents Med. Chem. 2015, 15, 631. (e) Kumar, S.; Bawa, S.; Gupta,
H. Biological activities of quinoline derivatives. Mini-Rev. Med. Chem. 2009, 9, 1648.
(2) To inform about mentioned method please see: (a) Batista, V. F.; Pinto, D. C.; Silva, A. M.
Synthesis of quinolines: A green perspective. ACS Sustainable Chem. Eng. 2016, 4, 4064. (b).
Prajapati, S. M.; Patel, K. D.; Vekariya, R. H.; Panchal, S. N.; Patel, H. D. Recent advances in the
synthesis of quinolines: a review. RSC Adv. 2014, 4, 24463.
(3) (a) Zhou, W.; Lei, J. Palladium-catalyzed synthesis of polysubstituted quinolines from 2-amino
aromatic ketones and alkynes. Chem. Commun. 2014, 50, 5583. (b) Pandit, R. P.; Lee, Y. R. Copper (II)
triflate-catalyzed reactions for the synthesis of novel and diverse quinoline carboxylates. RSC Adv.
2013, 3, 22039. (c) Yaragorla, S.; Pareek, A. Regioselective intramolecular annulations of ambident β-
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Page 24 of 26
enamino esters: A diversity-oriented synthesis of nitrogen-containing privileged molecules. Tetrahedron
Lett. 2018, 59, 909. (d) Cai, S.; Zeng, J.; Bai, Y.; Liu, X. W. Access to quinolines through gold-
catalyzed intermolecular cycloaddition of 2-aminoaryl carbonyls and internal alkynes. J. Org. Chem.
2011, 77, 801. (e) Chanda, T.; Verma, R. K.; Singh, M. S. InCl3-driven regioselective synthesis of
functionalized/annulated quinolines: Scope and limitations. Chem. asian J. 2012, 7, 778. (f) Gal'pern,
M. G.; Kudrevich, S. V.; Novozhilova, I. G. Synthesis and spectroscopic properties of soluble aza
analogs of phthalocyanine and naphthalocyanine. Chem. Heterocycl. Compd. 1993, 29, 49.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(4) (a) Ruggli, P.; Hindermann, P.; Frey, H. 4, 6-Dinitro‐und Diamino-isophtalaldehyd II; lin.
Benzo‐di‐α‐picolin und Benzo‐di‐pyridin. 35. Mitteilung über Stickstoff‐Heterocyclen. HeIv. Chim.
Acta 1938, 21, 1066. (b) Ruggli, P.; Reichwein, H. Über 4, 6‐Diamino‐1, 3‐diacetyl‐benzol und seine
Überführung in Derivate des lin. Benzo‐dipyridins. HeIv. Chim. Acta 1937, 20, 905. (c) Ruggli, P.;
Preiswerk, E. Über lineare und angulare Benzo‐dipyridine VI (1, 5‐Anthrazoline und 4,
5‐Phenanthroline). HeIv. Chim. Acta 1939, 22, 478. (d) Ruggli, P.; Brandt, F. Über ein neues lineares
Benzo‐dipicolin, das 2, 6‐Dimethyl‐1, 5‐anthrazolin. HeIv. Chim. Acta 1944, 27, 274.
(5) (a) Mohammadpoor-Baltork, I.; Tangestaninejad, S.; Moghadam, M.; Mirkhani, V.; Anvar, S.;
Mirjafari, A. Microwave-promoted alkynylation-cyclization of 2-aminoaryl ketones: a green strategy for
the synthesis of 2, 4-disubstituted quinolines. Synlett, 2010, 20, 3104. (b) Anvar, S.; Mohammadpoor-
Baltork, I.; Tangestaninejad, S.; Moghadam, M.; Mirkhani, V.; Khosropour, A. R.; Kia, R. Efficient and
environmentally-benign three-component synthesis of quinolines and bis-quinolines catalyzed by
recyclable potassium dodecatungstocobaltate trihydrate under microwave irradiation. RSC Adv. 2012, 2,
8713. (c) Anvar, S.; Mohammadpoor-Baltork, I.; Tangestaninejad, S.; Moghadam, M.; Mirkhani, V.;
Khosropour, A. R.; Landarani Isfahani, A.; Kia, R. New pyridinium-based ionic liquid as an excellent
solvent–catalyst system for the one-pot three-component synthesis of 2,3-disubstituted quinolines. ACS
Comb. Sci. 2014, 16, 93 (d) Asadi, B.; Landarani-Isfahani, A.; Mohammadpoor-Baltork, I.;
Tangestaninejad, S.; Moghadam, M.; Mirkhani, V.; Rudbari, H. A. Microwave-assisted, regioselective
ACS Paragon Plus Environment
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Page 25 of 26
The Journal of Organic Chemistry
one-pot synthesis of quinolines and bis-quinolines catalyzed by Bi(III) immobilized on triazine
1
2
3
dendrimer stabilized magnetic nanoparticles. Tetrahedron Lett. 2017, 58, 71.
4
5
6
7
8
(6) Rahmani, F.; Mohammadpoor-Baltork, I.; Khosropour, A. R.; Moghadam, M.; Tangestaninejad,
S.; Mirkhani, V. Propylphosphonium hydrogen carbonate ionic liquid supported on nano-silica as a
reusable catalyst for the efficient multicomponent synthesis of fully substituted pyridines and bis-
pyridines. RSC Adv. 2015, 5, 39978.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(7) (a) Kim, Y. J.; Varma, R. S. Microwave-assisted preparation of imidazolium-based
tetrachloroindate(III) and their application in the tetrahydropyranylation of alcohols. Tetrahedron Lett.
2005, 46, 1467. (b) Joseph, J. K.; Jain, S. L.; Singhal, S.; Sain, B. Efficient synthesis of 3,4-
dihydropyrimidinones in 1-n-Butyl-3-methylimidazolium tetrachloroindate (BMI·InCl4). Ind. Eng.
Chem. Res. 2011, 50, 11463. (c) Brown, L. C.; Hogg, J. M.; Swadźba-Kwaśny, M. Lewis acidic ionic
liquids. Top Curr. Chem. (Z) 2017, 375, 78.
(8) Edens, M.; Boerner, D.; Chase, C. R.; Nass, D.; Schiavelli, M. D. J. Org. Chem. 1977, 42, 3403.
(9) Imai, Y.; Johnson, E. F.; Katto, T.; Kurihara, M.; Stille, J. K. Synthesis of aromatic polymers
containing anthrazoline and isoanthrazoline units. J. Polym. Sci. Part A: Polym. Chem. 1975, 13, 2233.
(10) Jaffe, H. H.; Freedman, L. D. The ultraviolet absorption spectra of arylphosphonic and
diarylphosphinic acids. J. Am. Chem. Soc. 1952, 74, 1069.
(11) Ross, M. B.; Schatz, G. C. Aluminum and indium plasmonic nanoantennas in the ultraviolet. J.
Phys. Chem. C 2014, 118, 12506.
(12) Krajczyk, L.; Jabłoński, J. M.; Nyk, M.; Stręk, W.; Misiewicz, J. TEM study of indium and
gallium nitride nanocrystals in silica gasses obtained by the sol-gel method. J. Microsc. 2006, 223, 231.
(13) Bagdi, A. K.; Santra, S.; Rahman, M.; Majee, A.; Hajra, A. Synthesis of polysubstituted
quinolines via copper (II)-catalyzed annulation of 2-aminoaryl ketones with alkynoates. RSC Adv. 2013,
3, 24034.
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The Journal of Organic Chemistry
Page 26 of 26
(14) Qandalee, M.; Alikarami, M.; Mighani, H.; Asghari, S.; Beikjani, Sh.; Hatami, M. Unexpected
simultaneous synthesis of trisubstituted quinolines and acylhydrazones under catalyst-free conditions.
Int. nano Lett. 2013, 3, 1.
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2
3
4
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7
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10
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23
24
25
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27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
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