One-pot Synthesis of Pyranoquinoline Derivatives Using a New Nanomagnetic Catalyst Supported on Functionalized 4-Aminopyridine (AP) Silica

Full text of DOI:10.1080/00304948.2020.1779566

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/uopp20
One-pot Synthesis of Pyranoquinoline Derivatives
Using a New Nanomagnetic Catalyst Supported on
Functionalized 4-Aminopyridine (AP) Silica
Amir Shabanloo , Ramin Ghorbani-Vaghei & Sedigheh Alavinia
To cite this article: Amir Shabanloo , Ramin Ghorbani-Vaghei & Sedigheh Alavinia (2020): One-
pot Synthesis of Pyranoquinoline Derivatives Using a New Nanomagnetic Catalyst Supported on
Functionalized 4-Aminopyridine (AP) Silica, Organic Preparations and Procedures International,
DOI: 10.1080/00304948.2020.1779566
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ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
https://doi.org/10.1080/00304948.2020.1779566
EXPERIMENTAL PAPER
One-pot Synthesis of Pyranoquinoline Derivatives Using a
New Nanomagnetic Catalyst Supported on Functionalized
4
-Aminopyridine (AP) Silica
Amir Shabanloo, Ramin Ghorbani-Vaghei, and Sedigheh Alavinia
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
ARTICLE HISTORY Received 3 December 2018; Accepted 27 March 2020
Multi-component reactions (MCRs) are important tools in combinatorial chemistry
because of their capability to prepare target compounds in high yields with superior
1
atom economy. Heterogeneous catalysts have attracted renewed attention over homoge-
2
–3
neous catalysts, because of their simplicity in recovery and regeneration.
In some
4
ways, nano catalysts act as a bridge between heterogeneous and homogeneous catalysts.
Moreover, magnetic nanoparticles (MNPs) offer such benefits as high stability, facile
separation by an external magnetic field, easy preparation and functionalization, and
5–6
environmental benignity; they have high surface area and high loading capacity.
In
continuation of our investigations on the application of metal nanoparticles as heteroge-
7
–10
neous catalysts in organic reactions,
we now describe in this study an efficient
method for the one-pot synthesis of pyranoquinoline derivatives from aryl aldehydes,
11
malononitrile, and 8-hydroxyquinoline. We used MNPs@SiO -Pr-AP for our work.
2
We sought to enrich the diversity of pyranoquinoline chemistry while still maintain-
12–13
ing those aspects of structure that lead to useful activities.
One of the best known
pyranoquinoline scaffolds is 2-amino-4H-pyranoquinoline. Biological properties of its
1
4
15
16
derivatives include anti-microbial, cardiotonic, anti-inflammatory, and anti-tumor
1
7
properties. A number of methods deal with the synthesis of 2-amino-4H-pyranoquino-
lines using such catalysts as pyridine, piperidine, KF/Al O , DABCO, and
MgO. These methods are useful, but some of them have their own drawbacks, includ-
ing the need for lessening their environmental impact using the principles of green
1
8
19
20
21
2
3
2
2
2
3–24
chemistry.
In this context, we now introduce MNPs@SiO -Pr-AP as a highly effi-
2
cient, reusable and heterogeneous catalyst for the preparation of 2-amino-4H-pyrano-
quinolines at room temperature under solvent-free conditions (Scheme 1).
The Fe O MNPs and their chloro-functionalized silica coated magnetic nanoparticles
3
4
(
Fe O @SiO -(CH ) -Cl) were prepared following a known method (see Scheme 2 and
3 4 2 2 3
1
1
Experimental section). The MNPs@SiO -Pr-AP nanoparticles were characterized by
2
FT-IR, SEM, TGA, XRD, and EDX. The latter data are available from the corresponding
author upon request. In this report, we focus on the catalytic activity of the nanopar-
ticles. Fig. 1 shows that these nanoparticles are nearly spherical with nano-dimension.
CONTACT Ramin Ghorbani-Vaghei
rgvaghei@yahoo.com
Department of Organic Chemistry, Faculty of Chemistry,
Bu-Ali Sina University, Hamedan, Iran
Supplemental data for this article can be accessed here.
ß 2020 Taylor & Francis Group, LLC

2
A. SHABANLOO ET AL.
Scheme 1. Three-component one-pot reaction for the the synthesis of pyranoquinoline.
Scheme 2. The preparation of the nanocatalyst.
The peaks of iron, oxygen, nitrogen, carbon, and silica can be detected that confirmed
the presence of these elements in the structure of the catalyst (Fig. 2).
We studied the effectiveness of our catayst on the reaction of Scheme 1. The effects
of different parameters including catalyst loading, solvent and temperature were studied
on a model reaction as summarized in Table 1. In the model, we ran the reaction of
benzaldehyde (1 mmol), malononitrile (1 mmol), and 8-hydroxyquinoline (1.2 mmol) in
the presence or absence of MNPs@SiO -Pr-AP. It was observed that the reaction could
2
not proceed without the catalyst even after a prolonged reaction time (Table 1, entry 1).
Various amounts of the catalyst were examined (Table 1, entries 2-7). The best result
was obtained in the presence of 70 mg of catalyst under solvent-free conditions (Table
1
6
, entry 6). No improvements were observed by reducing the amount of catalyst to
0 mg (Table 1, entry 5). The effects of several solvent systems on the reaction times
and yields of the product were tested (Table 1, entries 8-10). The superior effectiveness
of MNPs@SiO -Pr-AP over Fe O @SiO (20 mg) was clearly observed (Table 1,
2
3
4
2
entry 11).

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
3
Figure 1. SEM image of MNPs@SiO -Pr-APbefore reaction.
2
Figure 2. The EDX analysis of the synthesized catalyst.
After finding suitable conditions, several substituted aldehydes were examined in the
procedure and the results are shown in Table 2. Yields were not particularly sensitive to
the effect of substitution or to electron-rich or electron-poor aldehydes. All of the reac-
tions were complete within 10-45 min. This suggests that the one-pot reaction may be
quite general and has a good substrate scope.
The recyclability of the catalyst was studied in the model reaction. The reusability of
MNPs@SiO -Pr-AP was tested through seven cycles, with percentage yields of 98, 97,
2
9
6, 96, 95, 94 and 91 respectively for the synthesis of 2-amino-4H-pyrano[3,2-h] quin-
oline under the optimized reaction conditions (Fig. 3). Furthermore, Fig. 4 displays the
SEM image of the catalyst after five consecutive reactions. We see the catalyst ranging
from 41 to 82 nm in size; the image suggests that the morphology of spherical nanopar-
ticles was saved without change during the organic reactions.

4
A. SHABANLOO ET AL.
Table 1. Optimizing the reaction conditions.
a
Entry
Catalyst (mg)
Conditions
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
—————
Solvent-free, r.t.
Solvent-free, r.t.
Solvent-free, r.t.
Solvent-free, r.t.
Solvent-free, r.t.
Solvent-free, r.t.
Solvent-free, r.t.
EtOH, reflux
12 h
60
30
45
40
30
30
40
50
50
37
32
34
45
68
79
96
96
75
85
73
65
b
MNPs@SiO
MNPs@SiO
MNPs@SiO
MNPs@SiO
2
2
2
2
-Pr-AP (30 b)
-Pr-AP (40)
b
-Pr-AP (50)b
-Pr-AP (60)
b
MNPs@SiO
2
-Pr-AP (70b)
MNPs@SiO
MNPs@SiO
MNPs@SiO
MNPs@SiO
2
-Pr-AP (80)
-Pr-AP (70)
-Pr-AP (70)
2
2
2
H
2
O/EtOH (1:1), reflux
CH CN, reflux
Solvent-free, rt
1
1
a
0
1
-Pr-AP (70)
3
b
3 4 2
Fe O @SiO (20)
Isolated yield.
b
Reaction conditions: benzaldehyde (1 mmol), malononitrile (1 mmol), and 8-quinolinol (1.25 mmol), solvent-free.
To show the utility of this method, the obtained results for the synthesis of 4a were
compared with other methods which have been reported for the synthesis of the same
products previously (Table 3). As can be seen, the selected compound was synthesized
in short times with high yields in the presence of the title catalyst.
In summary, we have introduced MNPs@SiO -Pr-AP as a reusable, stable and hetero-
2
geneous catalyst for the one-pot multi-component reaction of aldehydes, malononitrile,
and 8-hydroxyquinoline to prepare pyranoquinoline derivatives. The promising merits
of the present method are its generality, high product yields, short reaction times, sim-
ple workup procedures and reusability of the catalyst.
Experimental section
All commercially available chemicals were purchased from Merck and Fluka companies.
Nuclear magnetic resonance (NMR) spectra were recorded in DMSO-d on Bruker Avance
6
1
13
spectrometers (400 MHz for H NMR and 100 MHz for C NMR) using TMS as an
internal standard; chemical shifts were expressed in parts per million (ppm). Infrared (IR)
spectra were recorded on a Perkin Elmer GX FT-IR spectrometer. Mass spectra were
recorded on a Shimadzu QP 1100 BX Mass Spectrometer. Melting points were determined
on a Stuart Scientific SMP3 apparatus. The chemical structure of the synthesized catalyst
and prepared compounds were investigated with a Shimadzu Fourier transform infrared
spectrophotometer (FT-IR-470, Japan). Size and morphology of the prepared nanoparticles
were examined under a Philips XL 30 scanning electron microscope (SEM,
Netherlands).The qualitative analysis of MNPs@SiO -Pr-AP was performed by using
2
energy-dispersive X-ray spectroscopy (EDX). Energy dispersive X-ray analysis of the pre-
pared catalyst was performed on a FESEM-SIGM instrument. Thermo-gravimetric analysis
(TGA) was performed on a PYRIS DIAMOND instrument. Ultrasonication was done in a
2200 ETH-SONICA ultrasound cleaner with a frequency of 45 kHz.
1
1
Synthesis of MNPs@SiO -Pr-AP
2
The Fe O MNPs and their chloro-functionalized silica coated magnetic nanoparticles
3
4
25
(
Fe O @SiO -(CH ) -Cl) were prepared following a known method. Firstly, Fe O
3 4 2 2 3 3 4
2þ
3
þ
2þ
3þ
MNPs were prepared by co-precipitation of Fe and Fe ions with the [Fe ]/[Fe ]

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
5
Table 2. Synthesis of 2-amino-4H-pyranoquinolines.
ꢁ
ref
Comp
Aldehyde
Product
Time (min)
30
Yield (%)
96
m.p ( C) (lit. mp
)
1
1
4
a
211-213 (224-226 )
1
1
4
b
35
30
88
97
237-239 (237-239 )
1
1
4
c
197-200 (197-200 )
1
1
4
4
d
e
40
45
97
94
285-288 (285-289 )
1
1
218-221 (216-220 )
1
1
4
4
f
30
35
93
94
299-301 (300-302 )
1
1
g
210-204 (198-200 )
1
1
4
4
4
h
i
10
25
25
96
96
93
290-293 (292-296 )
1
1
299-301(295-298 )
1
1
j
274-276 (261-263 )
molar ratio of 2:1. In brief, FeCl ꢀ6H O (5.83 g) and FeCl ꢀ4H O (2.147 g) were dis-
3
2
2
2
ꢁ
solved in deionized (DI) water (100 mL) at 80 C under a N atmosphere with vigorous
2
stirring. Then, 10 mL of 25% NH OH was added dropwise to the reaction mixture at a
4
ꢂ1
constant drop rate of 1 mLmin in order to gain small and uniform Fe O MNPs.
3
4

6
A. SHABANLOO ET AL.
Figure 3. Recyclability of theMNPs@SiO -Pr-AP.
2
Figure 4. SEM images of MNPs@SiO -Pr-AP after five consecutive reactions.
2
After 30 min of stirring the reaction mixture, the reaction was completed and the mix-
ture was cooled to room temperature. The precipitated black particles of Fe O were
3
4
washed twice with DI water (250 mL) and a 0.02 M solution of NaCl (100 mL). The par-
ticles were decanted each time using an external magnet. Due to instability of Fe O4
3
MNPs under acidic conditions, a silica layer was coated on the surface of the synthe-
sized particles. The synthesized MNPs (1.0 g) was homogeneously dispersed in 500 mL
ꢁ
of ethanolic ammonia (25 mL, 25 wt %), under stirring at 80 C followed by dropwise
ꢁ
addition of an ethanolic solution of TEOS (10.8% v/v). After stirring at 80 C for 2 h,
the Fe O @SiO nanoparticles were obtained and washed several times with a mixture
3
4
2
ꢁ
of water–ethanol (1:1). Then, the synthesized nanoparticles were dried at 100 C for 5 h.
The color of the synthesized Fe O @SiO nanoparticles was dark brown. The chloro-
3
4
2
functionalized silica coated Fe O nanoparticles (Fe O @SiO -(CH ) -Cl) were synthe-
3
4
3
4
2
2 3
sized by treating the Fe O nanoparticles with 3-chloropropyltrimethoxysilane (CPTMS)
3
4
in 50 mL of toluene under sonication for 30 min. Then, the reaction mixture was stirred

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
7
Table 3. Comparison of the activity of MNPs@SiO -Pr-AP with other catalysts used to make 4a.
2
Entry
Conditions
Yield(%)(Ref)
ꢁ
25
1
2
3
5
6
Ce-Zr/SiO
2
, ethanol, 70 C, 2 h
94
95
95
78
ꢁ
19
Piperidine, ethanol, 100 C, 2h
ꢁ
ꢁ
21
DABCO, H
KF-Al
MNPs@SiO
2
O:EtOH; 80 C, 1 h
,ethanol, 100 C, 5 h
20
2
O
3
This work
2
-Pr-AP, solvent-free, room temperature, 30 min
96
ꢁ
under a nitrogen atmosphere at 80 C for 24 h to obtain the chloro-functionalized
Fe O @SiO nanoparticles. The resulting Fe O @SiO -(CH ) -Cl MNPs were decanted
3
4
2
3
4
2
2 3
by using an external magnet, repeatedly washed with ethanol, and dried at room tem-
perature. Finally, the Fe O @SiO @Cl–NPs were reacted with 4-aminopyridine to
3
4
2
achieve MNPs@SiO -Pr-AP. Synthesis of MNPs@SiO -Pr-AP was carried out by the
2
2
post-synthesis grafting method. At first, 1.0 g of synthesized MNPs was dispersed in
ꢁ
5
0 mL of DMF by stirring for 0.5 h at 50 C. After that, 0.94 g of 4-aminopyridine was
ꢁ
added to the mixture. The mixture was heated up to 90 C and stirred for 48 h. After
4
8 h, the solid product was filtered and washed with DMF several times and was dried
ꢁ
at 60 C.The MNPs@SiO -Pr-AP nanoparticles were characterized by FT-IR, SEM,
2
TGA, XRD, and EDX. Characterization data were submitted for review and are available
from the corresponding author upon request.
General procedure for the synthesis of pyranoquinolines using MNPs@SiO -Pr-AP
2
A mixture of aryl aldehyde (1 mmol), malononitrile (1 mmol, 66 mg) and 8-quinoline
(
1.25 mmol, 174 mg) in the presence of MNPs@SiO -Pr-AP (70 mg) was stirred at room
2
temperature for the appropriate time as mentioned in Table 2, monitored by thin layer
chromatography (silica gel, n-hexane/ethylacetate, 11/3). After completion of the reac-
tion, an external super magnet was used to separate the nano catalyst. Then, ethanol
(95%, 5 mL) was added and the product was recrystallized. All of the products are
known and were identified on the basis of comparison of their melting points with lit-
1
3
erature values. In addition, IR, H-NMR, C-NMR and LRMS spectra were submitted
for each compound for review. For the sake of completeness, spectroscopic data are
shown for compound 4a below.
2
-Amino-4-phenyl-4H-pyrano[3,2-h] quinoline-3-carbonitrile (4a)
Yield: 63 mg, 96%. FT-IR (KBr): 3466, 3324, 3189, 3019, 2191, 1653, 1626, 1596, 1467,
ꢂ1
1
1
245, 1048, 744 cm . H-NMR (DMSO-d 400 MHz): dH (ppm) 4.95 (s, 1H, CH),
6,
7
.20–7.34 (m, 7H, NH & Ph), 7.59-7.65 (m, 3H, Ph), 8.34 (dd, J ¼ 1.2, 1H, Ph), 8.95
2
1
3
(dd, J ¼ 1.6 Hz, 1H, Ph). C-NMR (DMSO-d6, 100 MHz): d (ppm) 160.28, 150.22,
C
1
1
45.62, 142.96, 137.45, 136.00, 128.98, 128.73, 128.52, 127.66, 126.99, 126.93, 123.57,
22.14, 121.94, 120.44, 55.92, 41.07; Mass (m/z): 299, 255, 222, 195, 167, 140, 116, 77.
Acknowledgment
We are thankful to Bu-Ali Sina University, Center of Excellence in Development of
Environmentally Friendly Methods for Chemical Synthesis (CEDEFMCS), for financial support.

8
A. SHABANLOO ET AL.
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