One-pot synthesis of 2-amino-4: H -chromene derivatives by MNPs@Cu as an effective and reusable magnetic nanocatalyst

Article abstract of DOI:10.1039/c9ra01679a

In this research, MNPs@Cu as an effective and recyclable nanocatalyst was prepared and characterized using different methods including Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM),

Full text of DOI:10.1039/c9ra01679a

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One-pot synthesis of 2-amino-4H-chromene
derivatives by MNPs@Cu as an effective and
reusable magnetic nanocatalyst†
Cite this: RSC Adv., 2019, 9, 12801
a
b
c
d
Wanzheng MA, Abdol Ghaffar Ebadi, Mostafa shahbazi sabil, Ramin Javahershenas
e
and Giorgos Jimenez
*
In this research, MNPs@Cu as an effective and recyclable nanocatalyst was prepared and characterized
using different methods including Fourier transform infrared spectroscopy (FT-IR), thermogravimetric
analysis (TGA), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), energy
dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). After the characterization of this new
nanocatalyst, it was efficiently used for the promotion of the one-pot synthesis of 2-amino-4H-
chromene derivatives via one-pot three-component reaction of the enolizable compound,
Received 5th March 2019
Accepted 1st April 2019
ꢀ
malononitrile, and arylaldehydes under solvent-free conditions at 90 C. The procedure gave the desired
products in high-to-excellent yields in short reaction times. Also this catalyst, because of its magnetic
nature, can be simply restored by a permanent magnetic field and comfortably reused several times
without any significant loss of its catalytic activity.
DOI: 10.1039/c9ra01679a
rsc.li/rsc-advances
13–16
more important.
Natural resources for preparing these
Introduction
compounds are limited and, in most cases, it is required to
Heterocyclic compounds have wide applications and are handle a difficult process for the isolation and purication of
essential in various pharmaceutical compounds. One of the key them. Therefore, to synthesize compounds from this group,
reasons for the widespread use of heterocyclic compounds is many efforts have been made to investigate derivatives progress
1
7–25
constructing various structures to achieve the desired func- and their medicinal features.
Many procedures have been
1,2
tions. Oxygen-bearing heterocyclic molecules such as 4H- developed for the preparation of functionalized 2-amino-4H-
pyrans and 4H-pyran-annulated heterocyclic scaffolds (4H- chromenes via one-pot Knoevenagel condensation of C–H-
chromene moieties) are very important because of their ubiq- activated acids, aldehydes, and malononitrile using catalysts
uitous presence in nature and provision of appropriate biolog- such as SDS, DAHP, MNP@AVOPc, [Sipim]HSO nano
ical activity, which make them an interesting issue for many Al O , POPINO, CuO nanoparticles and TBBDA. Some of
2 3
17
26
27
28
4
32
,
29
30
31
researchers in organic chemical science. These structural these procedures suffer from one or more limitations, such as
motifs are very benecial derivatives that develop activities such low yields of the desired product, long reaction times, toxicity,
as anti-HIV, anti-tumor, antimicrobial, anti-inammatory, poor recovery and reusability of the catalyst, and tedious work-
antifungal, and anti-allergenic with respect to the available up. Therefore, a great demand still exists for simple, versatile,
3–12
substituents in the structure.
Moreover, it has been observed that pyran-containing amino-4H-chromene derivatives under simple conditions.
heterocyclic compounds are widespread in nature and their
In green chemistry, scientists are trying to develop, design,
and environmentally friendly processes for the synthesis 2-
uses in pharmaceuticals, biodegradable agrochemicals, and implement ways to prevent the use or generation of
pigments, and cosmetics industries are becoming more and hazardous substances in chemical processes. Although inno-
vation processes with environmentally friendly solvents provide
a
a perfect solution to overcome these problems, in most cases,
the solvent-free conditions in chemical processes play an inev-
itable role. Nowadays, solvent-free procedures in the existence
Resource and Environmental Engineering College, Anhui Science and Technology
University, Fengyang 233100, China
b
Department of Agriculture, Jouybar Branch, Islamic Azad University, Jouybar, Iran
c
Department of Chemical Engineering, Graduated from Petroleum University of Ahvaz, of magnetic nanoparticles as a catalyst have eliminated most of
Iran
d
the problems associated to the use of organic solvents for
avoiding tedious separation procedures through extraction or
Department of Organic Chemistry, Faculty of Chemistry, Urmia University,
5
756151818, Urmia, Iran
distillation. Metal-catalysis has played a fundamental role in the
e
University of Tirana, Tirana, Albania. E-mail: jimenezgiorgos@gmail.com
33
prosperity of the industry. The utilization of transition-metal
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c9ra01679a
nanoparticles in catalysis is denitive as they assume metal
1
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surface activation and catalysis at the nanoscale and thereby accomplished using an SEM-LEO 1430VP analyzer. Magnetic
34–37
afford efficiency and selectivity to heterogeneous catalysis.
susceptibility measurements were accomplished using
Magnetic nanoparticles and analysis of their manipulation in a vibrating sample magnetometer (VSM/AGFM, MDK Co, Ltd,
the manufacturing of ne heterogeneous catalysis synthesis Iran) in the magnetic eld range of ꢁ8000 Oe to 8000 Oe at
have achieved a major area of research as an effective material ambient temperature. Magnetic susceptibility measurements
because of their good stability, low toxicity, easy synthesis, and were performed by a VSM/AGFM (MDK Co, Ltd, Iran) in the
3
8–42
ꢀ
functionalization, and large surface area.
Due to lose dis- magnetic eld range of ꢁ8000 Oe to 8000 Oe at 25 C. Elemental
persibility and catalytic activity through anisotropic dipolar analyses were carried out on a Carlo-Erba EA1110CNNO–S
attraction of the Fe
3 4
O nanoparticles, these kinds of uncoated analyzer and agreed (within 0.30) with the calculated values.
nanoparticles with metal oxides can be easily aggregate into
43
large clusters. The acidic environment also causes the loss of
their magnetic properties. It is essential to note that relatively
Catalyst synthesis
Preparation of MNPs. This precursor was prepared accord-
ing to the chemical co-precipitation method. To prepare MNPs,
3 4
small Fe O nanoparticles may tolerate rapid biodegradation
44
when they are directly exposed to biological systems. The
3 2 2 2
5.2 g of FeCl $6H O and 2 g of FeCl $4H O were poured into
suitable coating with a protective shell of silica to form a core–
a 250 mL ask reaction containing 40 mL deoxygenated water
followed by adding 0.9 mL of concentrated HCl under
a continuous ow of nitrogen gas. Next, 250 mL of NaOH
solution (1.5 M) was poured dropwise into the reaction solution
and stirred until the reaction was completed. Aer this period,
the resulting black MNPs were magnetically separated and
45
shell structure is essential to overcome such limitation.
Therefore, the use of magnetic coated nanoparticles as suitable
alternative supports for the functionalization of organic
compounds in the preparation of heterogeneous catalysis is of
paramount importance.
ꢀ
rinsed with deionized water and dried at 40 C for 24 h.
2
Preparation of MNPs@SiO . About 1 g of MNPs was
dispersed in a mixture containing water (5 mL), ethanol (45
mL), and concentrated aqueous ammonia (3 mL, 25 wt%) by
Experimental
General
All the pure chemicals were prepared from Merck and Fluka ultrasonication. Next, 0.5 mL of tetraethylorthosilicate (TEOS)
chemical companies. Separation and purication of the prod- was poured and the mixture was mechanically stirred for 24 h at
ucts were performed with extraction and recrystallization tech- room temperature. Aer this period, the precipitates of core–
niques. Melting points were determined with an shell MNPs@SiO nanoparticles were collected by an external
2
Electrothermal-9100 apparatus and no correction was made. magnetic and washed several times with ethanol. Finally, the
ꢀ
FT-IR spectra were obtained by means of a PerkinElmer PXI MNPs@SiO
spectrometer in KBr wafers. TGA analysis was conducted using for 5 h.
2
precipitate was dried under vacuum oven at 70 C
a TGA thermoanalyzer (PerkinElmer) instrument. Samples were
Preparation of MNPs bonded propyl chloride (MNPs@PC).
In the following step, 1 g of core–shell Fe @SiO nano-
ꢀ
ꢀ
ꢁ1
heated from 25 to 800 C at ramp 10 C min under an N
2
3
O
4
2
atmosphere. The X-ray diffraction (XRD) measurements of particles was dispersed in 20 mL dry toluene with the aid of
catalyst were performed with a Siemens D-500 X-ray diffrac- ultrasonication for 20 min. Next, 2 mL of 3-chloropropyl-
tometer (Munich, Germany). Scanning electron microscopy was triethoxysilane (CPTCSi) was poured in to the reaction solution
Scheme 1 All stages of the MNPs@Cu synthesis.
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Fig. 1 FTIR spectra of MNPs, MNPs@SiO , MNPs@PC, MNPs@DE-
TA@piperidine, and MNPs@Cu.
Fig. 4 SEM image of MNPs@Cu.
2
Fig. 2 TGA curves of MNPs, MNPs@DETA, Cu(salal) and MNPs@Cu.
Fig. 5 EDX spectra of MNPs@Cu.
and the mixture was reuxed for 24 h under nitrogen atmo-
sphere. At the end of the reaction, the solid phase was separated
from the solvent by a powerful magnet and then washed several
times with ethanol and distilled water. Eventually, the resulted
product (MNPs@PC) was dried in a vacuum oven.
Fig. 3 VSM magnetization curves corresponding to the bare MNPs Fig. 6 The XRD patterns of MNPs, MNPs@DETA@piperidine, and
and MNPs@Cu.
MNPs@Cu.
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eliminate the unreacted excess of the organic compounds and
next dried in a vacuum oven.
Preparation of MNPs@DETA@piperidine. The prepared
MNPs@DETA (2 g) dispersed in 100 mL of acetonitrile was
mixed with 1-(2-chloroethyl) piperidine (3 g) and the resultant
ꢀ
mixture was agitated at 80 C for 12 h. The resultant solid
(MNPs@DETA@piperidine) was isolated using an external
magnet and rinsed with water several times to eliminate the
unreacted excess of the inorganic salts and next dried in
a vacuum oven.
Scheme 2 Synthesis of 2-amino-3-cyano-4H-pyran derivatives using
MNPs@Cu.
Coordination of Cu(II) with MNPs@DETA@piperidine. A
Preparation of MNPs bonded N-propyl diethylenetriamine
MNPs@DETA). The prepared MNPs@PC (2 g) was dispersed in
00 mL of dry toluene for 30 min through sonication. Then, it
was mixed with diethylenetriamine (5 mL) and triethylamine (1
mL) under reux and nitrogen atmosphere and agitated for
mixture of MNPs@DETA@piperidine (1 g) and [Cu(salal) ] (2 g)
2
(
1
was dissolved in 20 mL of ethanol and then was stirred for 24 h
under dry argon atmosphere. At the end of the reaction, the
resultant precipitate MNPs@Cu formed was separated by
ltration, washed twice with ethanol (15 mL) to remove
unreacted metal precursors, and dried under vacuum oven to

1
2 h. The resultant solid (MNPs@DETA) was isolated using
a permanent magnet and rinsed with ethanol several times to
Table 1 Optimization of the three-component reaction of 4-hydroxycoumarin (1), 4-chlorobenzaldehyde (2e), and malononitrile (3) under
a
various conditions
b
Entry
Solvent
Catalyst (mg)
Temp.
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
CH
CH
toluene
DMF
2
Cl
CN
2
MNPs@Cu/10
MNPs@Cu/10
MNPs@Cu/10
MNPs@Cu/10
MNPs@Cu/10
MNPs@Cu/10
—
MNPs@Cu/10
MNPs@Cu/10
MNPs@Cu/10
MNPs@Cu/10
MNPs@Cu/10
MNPs@Cu/5
Reux
Reux
Reux
Reux
Reux
Reux
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
20
25
53
59
59
63
69
77
Trace
80
87
95
95
92
64
25
91
85
78
3
H
2
O
EtOH
ꢀ
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
90 C
ꢀ
60 C
ꢀ
80 C
ꢀ
10
11
12
13
14
15
16
17
90 C
ꢀ
100 C
ꢀ
110 C
ꢀ
90 C
ꢀ
MNPs@Cu/10
MNPs@Cu/15
MNPs@DETA@piperidine/10
25 C
ꢀ
90 C
ꢀ
90 C
ꢀ
Cu(salal)
2
/10
90 C
a
Reaction conditions: 4-hydroxycoumarin (1 mmol), 4-chlorobenzaldehyde (1 mmol), malononitrile (1.1 mmol), and required amount of the
b
catalysts. The yields refer to the isolated product.
Scheme 3 One-pot three-component condensation of 4-hydroxycoumarin (1), various aldehydes (2), and malononitrile (3).
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a
Table 2 MNPs@Cu-catalyzed synthesis of 2-amino-3-cyano-pyrano[3,2-c] chromen-5(4H)-one (4) derivatives
b
ꢀ
ꢀ
Entry
Product
RCHO (2)
Product
Time (min)
Yield (%)
MP (obsd) ( C)
MP (lit.) ( C)
1
7
9
1
4a
12
91
258–260
256–258
260–262
1
2
4b
12
92
260–263
1
9
3
4
5
6
7
4c
4d
4e
4f
8
94
94
95
95
92
249–251
243–245
262–264
259–261
233–235
250–252
244–246
263–265
260–262
236–238
1
4
1
8
8
7
8
8
8
53
4g
15
4
1
1
4
6
8
7
7
8
9
4h
4i
20
15
20
15
15
90
93
90
92
90
240–243
222–224
226–229
256–259
261–264
242–244
221–223
228–230
253–254
260–262
1
1
1
0
1
2
4j
4k
4l
1
7
7
1
1
3
4m
15
90
250–252
252–254
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Table 2 (Contd.)
b
ꢀ
ꢀ
Entry
Product
RCHO (2)
Product
Time (min)
15
Yield (%)
95
MP (obsd) ( C)
MP (lit.) ( C)
4
2
7
1
4
4n
4o
258–260
261–264
259–261
265–267
1
1
5
20
89
a
Reaction conditions: 4-hydroxycoumarin (1 mmol), aldehyde (1 mmol), malononitrile (1.1 mmol), MNPs@Cu (10 mg).
obtain the pure product. All stages of the MNPs@Cu synthesis
are shown in Scheme 1.
Thermal analysis of MNPs@Cu. As observed in Fig. 2, the
thermal constancy of the MNPs, MNPs@DETA, Cu(salal) , and
2
MNPs@Cu were measured by thermogravimetric analysis (TGA)
ꢀ
ꢁ1
General procedure for the synthesis of 2-amino-4H-
chromenes (4, 6, 9 and 10)
under a nitrogen atmosphere at 10 C min of heating rate. The
ꢀ
ꢀ
TGA of Cu(salal) has three stages: below 250 C, 300–400 C,
and 400–500 C which is related with the decomposition of
salicylic chelate ligand. TGA data for another three samples
show approximately 5% weight loss below 200 C due to the
2
ꢀ
A mixture of, enolizable compound (1, 5, 7–8, and 1 mmol),
malononitrile (1.1 mmol), aldehyde (1 mmol), and MNPs@Cu
ꢀ
ꢀ
was combined with each other at 90 C under solvent-free
dehydration of the surface hydroxy groups as well as desorption
of physically adsorbed solvents. In the TGA graph of
MNPs@DETA, a mass percentage loss of about 9% appeared
that is related with the organic parts decomposition. The TGA of
MNPs@Cu undergoes four stages of thermal degradation with
a more mass loss at about 24.5%. In addition to the mentioned
conditions. The development of the reaction was controlled
with TLC analyses. At the end of the reaction, the mixture was
rinsed with water and next, recrystallized from ethanol to ach-
ieve the pure product.
Results and discussion
Catalyst characterization
ꢀ
step in the range below 250 C, the second stage can be seen in
ꢀ
the range between 300–400 C, which can be related to the
elimination of salicylic chelate ligand. The second stage occurs
FTIR analysis of MNPs@Cu. The corresponding FT-IR
ꢀ
in the range between 500–600 C which is attributed to forma-
spectra of the MNPs, MNPs@SiO
2
, MNPs@PC, MNPs@DE-
ꢀ
tion of a Fe–O–Cu bond and, nally, at 650 C because of the
TA@piperidine, and MNPs@Cu samples in the region of 400–
ꢁ
1
decomposition of MNPs.
4
3
000 cm
are presented in Fig. 1. The bands at 572 and
ꢁ
1
VSM analysis of MNPs@Cu. To investigate the magnetic
properties of the MNPs and MNPs@Cu, magnetic measure-
ments were performed by means of a vibrating sample
magnetometer (VSM) with the eld sweeping from ꢁ8500 to
+8500 Oersted at ambient temperature (Fig. 3). As shown in
389 cm in the Fe O MNPs are related to the Fe–O stretching
3
4
frequency and the OH groups attached to the iron, respectively.
ꢁ
1
In the case of MNPs@SiO
2
, the band's appeared at 1039 cm
can be ascribed to the stretching vibration of the Si–O groups. In
ꢁ1
about the MNPs@PC, the absorption bands at 2973 cm are
associated to the C–H stretching vibration mode. The obtained
FT-IR spectra for MNPs@DETA@piperidine contained charac-
VSM patterns, the saturation magnetization (M ) values of
s
ꢁ
1
MNPs and MNPs@Cu are 60.39 and 34.55 emu g , respectively.
SEM analysis of MNPs@Cu. The morphology and size of the
MNPs@Cu were surveyed to determine the variations in the
surface of this nanocatalyst by the SEM analysis (Fig. 4). The
SEM image of MNPs@Cu shows that the catalyst has a nearly
spherical structure with nanometer-sized particles.
ꢁ1
teristic amine stretching vibrations at 1634 cm related to
diethylene triamine and piperidine groups. In the case of
ꢁ1
ꢁ1
MNPs@Cu, the signals at 1634 cm are shied to 1625 cm
.
The results clearly proved the effective coordination of metal
groups with MNPs@DETA@piperidine.
Scheme 4 One-pot three-component reaction of dimedone (5), different aldehydes (2) and malononitrile (3).
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Table 3 MNPs@Cu-catalyzed synthesis of 2-amino-3-cyano-7,8-dihydro-4H-chromen-5(6H)-one (6)derivatives
b
ꢀ
ꢀ
Entry
Product
RCHO (2)
Product
Time (min)
Yield (%)
MP (obsd) ( C)
MP (lit.) ( C)
4
9
3
1
6a
17
91
232–234
234–235
214–216
2
2
3
4
5
6b
6c
6d
6e
15
15
15
15
94
92
95
93
216–219
180–182
207–210
212–214
25
24
23
179–180
198–200
215–217
3
2
2
6
7
6f
20
15
94
92
229–231
208–211
228–230
207–209
5
6g
49
52
50
49
8
9
6h
6i
15
15
25
25
95
92
91
90
207–209
225–229
217–220
203–205
210–211
227–230
220–222
201–202
1
1
0
1
6j
6k
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Table 3 (Contd.)
b
ꢀ
ꢀ
Entry
Product
RCHO (2)
Product
Time (min)
Yield (%)
MP (obsd) ( C)
MP (lit.) ( C)
5
9
1
2
3
6l
20
92
223–225
237–239
224–226
51
1
6m
25
20
94
92
238–240
26
1
4
6n
209–211
210–212
a
b
Reaction conditions: dimedone (1 mmol), aldehyde (1 mmol), malononitrile (1.1 mmol), MNPs@Cu (10 mg). The yields refer to Isolated
products.
EDX analysis of MNPs@Cu. Energy dispersive X-ray (EDX)
In current research, we reported our results for the efficient
mapping was carried out to verify the components of MNPs@Cu and rapid synthesis of 2-amino-3-cyano-4H-pyrans using
nanocatalyst (Fig. 5). The EDX analysis proved the presence of Fe, MNPs@Cu as an effective and reusable heterogeneous nano-
O, Si, C, N, and Cu characteristic peaks. Moreover, the appearance catalyst under solvent-free conditions (Scheme 2).
of copper bands in the nanocatalyst demonstrates the successful
immobilization of copper(II) complex on the MNPs surface.
To monitor the reaction conditions for synthesizing 2-
amino-4-(4-chlorophenyl)-3-cyano-pyrano[3,2-c] chromene-
XRD analysis of MNPs@Cu. X-ray diffraction (XRD) is an 5(4H)-one (4e), the inuence of the reaction temperature, the
effectual spectra method for the identication of the synthesis solvent, and the amounts of magnetic nanocatalyst were
of magnetite crystal phase in the magnetic nano-catalyst. Fig. 6 studied in the reaction of 4-hydroxycoumarin (1), 4-chlor-
exhibits the XRD patterns corresponding to the MNPs, obenzaldehyde (2e), and malononitrile (3) (molar ratio:
MNPs@DETA@piperidine, and MNPs@Cu. In the XRD patterns 1 : 1 : 1.1) as a model reaction. The outcomes are presented in
of the all samples, the reections at the values of 2q – which are Table 1. To obtain the optimal reaction solvent, different
3
6
0.27 (220), 35.34 (311), 43.73 (400), 54.45 (422), 57.51 (511), solvents such as H
3.19 (440), and 74.58 (533) – correspond to the spinel phase of in the existence of a certain amount of magnetic nanocatalyst
2 2 2 3
O, CH Cl , CH CN, DMF, toluene, and EtOH
magnetic iron oxide nanoparticles and are good agreement with were used. The trial reaction in the existence of EtOH, as
(
JCPDS card no. 79-0417). In the case of MNPs@DETA@piper- a solvent, afforded the highest percentage of the target product
ꢀ
idine, and MNPs@Cu, the broad reection in 2q ¼ 15–27 is 4e (Table 1, Entry 6) but the most favorable conditions in terms
related to an amorphous silica shell. Therefore, it is concluded of rate and yield were obtained under solvent-free conditions for
that the MNPs@Cu catalyst was synthesized successfully the reaction (Table 1, Entry 10). In the following phase of the
without damaging the crystalline structure of the MNPs core.
survey, the inuence of temperature on the completion of the
Scheme 5 One-pot three-component reaction of C–H-activated acids (7–8), different aldehydes (2) and malononitrile (3a).
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Table 4 MNPs@Cu catalyzed synthesis of 2-amino-3-cyano-4H-pyran (9–10) derivatives
b
ꢀ
ꢀ
Entry
Product
RCHO (2)
Product
Time (min)
Yield (%)
MP (obsd) ( C)
MP (lit.) ( C)
5
3
4
1
9a
20
91
94
237–239
233–230
236–238
231–232
5
2
3
4
5
6
9b
9c
9d
9e
9f
15
15
15
15
25
55
55
56
57
95
93
94
88
224–221
217–215
223–219
212–209
223–225
218–220
220–222
210–212
58
58
55
55
55
7
8
9
10a
10b
10c
10d
10e
25
20
20
20
20
91
92
93
92
94
276–280
242–245
258–261
253–256
276–279
279–282
245–247
258–259
254–255
278–279
1
1
0
1
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Table 4 (Contd.)
b
ꢀ
ꢀ
Entry
Product
RCHO (2)
Product
Time (min)
Yield (%)
MP (obsd) ( C)
MP (lit.) ( C)
58
1
2
10f
25
86
225–228
224–225
a
b
Reaction conditions: C–H-activated acid (7 and 8) (1 mmol), aldehyde (1 mmol), malononitrile (1.1 mmol), MNPs@Cu (10 mg). The yields refer to
isolated products.
reaction was investigated (Entries 8–12 and 14). Without heat- corresponding values for inputs 10, 16, and 17 accurately indi-
ing, the reaction rate was very low and the yield was negligible cates that the catalyst activity increases when MNPs@DETA@-
(
9
Table 1, Entry 14). The yield of the product increased up to piperidine is coordinate to the Cu(salal)
0 C (Table 1, Entries 8–10), aer which no enhancement was of nitrogen.
2
through the lone pair
ꢀ
observed by increasing the temperature (Table 1, Entries 11 and
In order to generalize the optimum conditions (Table 1,
1
2). To obtain the optimum amount of magnetic nanocatalyst Entry 10), we investigated the generality of this method with
MNPs@Cu, diverse concentrations of nanocatalyst (5, 10, and a range of appropriate aldehydes to prepare a series of 2-amino-
5 mg) were used to compare the reaction efficiency (Table 1, 3-cyano-pyrano[3,2-c] chromen-5(4H)-one derivatives (4a–o)
1
Entries 10, 13 and 15). Aer several screening tests with under similar conditions (Scheme 3). The optimized results are
different concentrations of the nanocatalyst, it was found that represented in Table 2. It was observed that the aryl aldehydes
the maximum yield (i.e., 95%) at the short reaction time was reacted very well with both electron-withdrawing and electron-
achieved when 10 mg of MNPs@Cu was applied under solvent- donating substituents and resulted the relating 2-amino-3-
free conditions (Entry 10). Enhancing the concentration of cyano-pyrano[3,2-c] chromen-5(4H)-one derivatives with high
catalyst beyond 10–15 mg did not lead to any substantial purity in good yields. The further precise analysis shows that
progress in the product yield (Table 1, Entry 15) whereas the aryl aldehydes having an electron-donating group (entries 7–15,
lower amount of catalyst needed for the reaction from 10 mg to Table 2) react slower compared to aryl aldehydes having elec-
5
1
mg led to reducing the efficiency of the reaction (Table 1, Entry tron withdrawing groups (entries 1–6, Table 2).
3). Without using the catalyst, the product yields fell sharply In the following, to expand the use of this nanomagnetic
and some stain was observed on thin-layer chromatography catalyst to the other reactions of these categories, a series of
TLC) (Table 1, Entry 7). Finally, when the model reaction was polyfunctionalized 2-amino-3-cyano-7,8-dihydro-4H-chromen-
(
accomplished in the presence of 10 mg of MNPs@DETA@pi- 5(6H)-one derivatives (6a–n) were prepared from the reaction
peridine and Cu(salal)2 under the optimized conditions, the mixture of dimedone (5), different aldehydes (2a–n), and
yield of the product were 85 and 78%, respectively (Table 1, malononitrile (3) under the optimized reaction conditions
Entries 16 and 17). The favourable comparison of the mentioned above (Scheme 4). In this case, the use of dimedone,
as an enolic component, improved the reaction time of the
desired product 6 slightly (Table 3).
Scheme 6 A plausible mechanism for the one-pot three-component
reaction of various enols (1, 5, 7,and 8), aldehydes (2), and malononi- Fig. 7 The recycling of MNPs@Cu as a nanomagnetic catalyst under
trile (3) catalyzed by MNPs@Cu under solvent-free conditions.
solvent-free conditions.
12810 | RSC Adv., 2019, 9, 12801–12812
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Table 5 Comparison of the current method with other reported strategies for synthesizing 2-amino-4-(4-chlorophenyl)-3-cyano-pyrano[3,2-
c] chromene-5(4H)-one
ꢀ
Entry
Catalyst
Catalyst loading
Solvent
Temp ( C)
Time (min)
Yield (%)
Ref.
1
2
3
4
5
6
7
8
9
SDS
20 mol%
15 mol%
20 mg
10 mol%
5 mol%
H
H
—
H
H
—
H
—
EtOH
H
H
H
EtOH
EtOH
DMF
2
2
O
O
60
100
25
25
Reux
90
25
100
25
Reux
100
80
Reux
Reux
25
150
6
15
420
10
8
240
30
300
170
5
88
93
94
93
96
95
85
90
89
91
94
89
80
93
81
17
31
27
59
CuO nanoparticles
MNP@AVOPc
Urea
POPINO
MNPs@Cu
DAHP
2
O/EtOH
O
2
30
10 mg
This work
10 mol%
0.08 mmol
25 mol%
0.18 mmol
10 mol%
10 mol%
10 mol%
10 mol%
250 mg
2
O/EtOH
26
28
29
32
60
61
62
63
64
[Sipim]HSO
4
Nano Al
TBBDA
DBU
t-ZrO
ZnO NPs
Sodium alginate
KF/Al
2
O
3
10
11
12
13
14
15
2
2
2
O/EtOH
O
O
2
NPs
38
10
50
60–180
a
a
a
2
O
3
a
Reaction conditions: dimedone (1 mmol), 4-chlorobenzaldehyde (1 mmol), malononitrile (1 mmol).
Aer the successful synthesis of 2-amino-3-cyano-7,8-dihy- tedious work-up procedures. It is clear that a suitable method-
dro-4H-chromen-5(6H)-one derivatives in good to excellent ology in terms of the compatibility with the environment,
yields, it was attempted to synthesize 2-amino-3-cyano-pyrano product yield, using green solvent, and reaction time in the
[
[
4,3-b] pyran-5(4H)-ones (9a–9f) and 2-amino-3-cyano-pyrano existence of a low catalyst loading of MNPs@Cu comparing with
3,2-c] pyridine-6(5H)-ones (10a–10f) under similar conditions. several other catalysts has been developed.
For this purpose, were placed the 4-hydroxy-6-methylpyrone 9
and 4-hydroxy-6-methylpyridone 10 compounds with dimedone
in the same conditions (Scheme 5). In this case, the use of C–H-
Conclusion
activated acids, as cyclic 1,3-dicarbonyls, required longer reac- In general, we described an easy, effective, and ecofriendly
tion times compared to 4-hydroxycoumarin (1) under similar method for a wide range of biologically and pharmacologically
reaction conditions (Table 4).
interesting functionalized 2-amino-4H-chromenes one in the
A plausible mechanism for the preparation of 2-amino-4H- existence of an environmental friendly and reusable nano-
chromene derivatives catalyzed by MNPs@Cu is shown in catalyst (MNPs@Cu) via one-pot Knoevenagel condensation of
Scheme 6. Initially, malononitrile 2 and aldehyde 3 as the C–H-activated acids, aldehydes, and malononitrile under
reactant components react with each other via a Knoevenagel solvent-free conditions. This method suggests various privileges
condensation reaction. MNPs@Cu coordinate with the C^N including the usage of a green catalyst, lower loading of the
and C]O functional groups of aldehyde and malononitrile, catalyst, no organic solvent, easy work-up, and good to high
respectively, thus increasing the activity of these groups. Aer yields.
passing the transition state 11 and a dewatering step, it creates
alkylidene malononitrile 12. Then, enolate of the C–H-activated
acid (1, 5, 7, and 8) by Michael addition is added to this acti-
Conflicts of interest
vated intermediate by MNPs@Cu and the polar transition state There are no conicts to declare.
13 is created. This compound is unstable and is converted by
tautomerization to the intermediate 14, which generates prod-
ucts 4, 6, 9, and 10 though cyclization reaction.
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