A novel and reusable ionically tagged nanomagnetic catalyst: Application for the preparation of 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitriles via vinylogous anomeric based oxidation

Article abstract of DOI:10.1016/j.mcat.2018.11.009

Herein, we report Fe₃O₄@O₂PO₂(CH₂)₂NH₃⁺CF₃CO₂^? as a novel and reusable ionically tagged nanomagnetic catalyst. It was characterized by

Full text of DOI:10.1016/j.mcat.2018.11.009

MolecularCatalysis463(2019)20–29
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.elsevier.com/locate/mcat
A novel and reusable ionically tagged nanomagnetic catalyst: Application
for the preparation of 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-
arylnicotinonitriles via vinylogous anomeric based oxidation
Fatemeh Karimi, Mohammad Ali Zolfigol⁎, Meysam Yarie
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
A R T I C L E I N F O
A B S T R A C T
−
Keywords:
Herein, we report Fe3O4@O2PO2(CH2)2NH3+CF3CO2 as a novel and reusable ionically tagged nanomagnetic
catalyst. It was characterized by several techniques including Fourier transform infrared (FT-IR) spectroscopy,
thermo gravimetric analysis/differential thermal analysis (TGA/DTA), scanning electron microscopy (SEM),
transmission electron microscopy (TEM), vibrating sample magnetometer (VSM) and energy dispersive X-ray
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-
arylnicotinonitrile
Anomeric effect
Anomeric based oxidation (ABO)
(EDX) analysis. The catalytic behaviour of the Fe3O4@O2PO2(CH2)2NH3+CF3CO2 was examined at the
−
Fe3O4@O2PO2(CH2)2NH3+CF3CO2
−
synthesis 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitrile derivatives. Experimental data has approved
that the final step of the plausible mechanism proceeded via a vinylogous anomeric based oxidation mechanism.
Described catalys shows excellent potential of recycling and reusing at the described multicomponent reaction.
Multicomponent reactions
Reusable nanomagnetic catalyst
Vinylogous anomeric based oxidation
1. Introduction
The effective and rapid synthesis of target molecules accompanied
with economic and ecological insight which is the paramount goal of
Homogeneous catalytic systems holding varied merits including
excellent activity, selectivity, high turnover numbers (TON) and turn
over frequencies (TOF). However, catalytic applications of homo-
geneous systems in industrial processes, particularly for the drug and
pharmaceutical industries are restricted because the extra purity of the
drugs is very important. This limitation comes from obstacles in the step
of the isolation and separation of homogeneous catalysts from the de-
sired products. An efficient strategy to overcome the difficulties con-
nected to cumbersome process of isolation and separation of the
homogeneous catalysts is their conversion to the corresponding het-
erogeneous analogous systems. This process creates a heterogeneous
catalytic system [1–4]. However, in the case of heterogeneous catalysts
due to the lower dimensionality of the interactions between reactant
and the surface of catalysts, the active sites are not as approachable as
in the case of homogeneous ones, and therefore the activity of the
heterogeneous catalysts is reduced. Although, nano-making of hetero-
geneous catalysts can enhance their activity and selectivity, but making
their separation tedious instead. Therefore, magnetization of the het-
erogeneous catalysts seems to be the most reasonable solution. Mag-
netic nanocatalysis presents a catalytic system which shows suitable
activity, selectivity, easy separation and recovery. This field of chem-
istry has been extensively reviewed [5–11].
one-pot multicomponent reactions. This excellent synthetic tool can be
an influential source of molecular diversity. One-pot multicomponent
strategy offers procedures with merits such as facile access to high le-
vels of diversity through a time-saving process with high atom and step
economy, waste prevention, and energy efficiency. Therefore, it ap-
pears that access to "ideal synthesis" through a one-pot multicomponent
process is realized for chemists [12–19].
Coumarin structural kernels have found an important role in phar-
maceutical industry as they can serve as antimicrobial, antioxidant,
antiamoebic, analgesic, anti-pyretic, and anticancer agents [20–22].
Also, these versatile molecules are applied as additives to food, cos-
metics, perfumes, laser dyes, optical brightener, and dispersed fluor-
escence [23,24].
On the other hand, N-heteroaromatic structures particularly pyr-
idine ring systems are ubiquitous in pharmaceutical active molecules
and natural products [25,26]. Among the N-heteroaromatic molecules,
2-amino-3-cyano pyridine scaffold represent fascinating biological
characteristics. These compounds can apply as A2A adenosine receptor
antagonists, IKK-β inhibitors, inhibitors of HIV-1 integrase, anti-mi-
crobial, anti-tumour, analgesic, anti-inflammatory, and antipyretic
agents [27–31]. Although, chromene-linked nicotinonitrile derivatives
present excellent biological activities but, only a few procedures
⁎ Corresponding author.
E-mail address: zolfi@basu.ac.ir (M.A. Zolfigol).
https://doi.org/10.1016/j.mcat.2018.11.009
Received 23 September 2018; Received in revised form 5 November 2018; Accepted 9 November 2018
2468-8231/©2018PublishedbyElsevierB.V.

F. Karimi et al.
MolecularCatalysis463(2019)20–29
mechanism leads to designing of task-specific biomimetic reactions in
the future.
2. Experimental
Scheme 1. Anomeric effect leads to bond-breaking in the case of 4-halo-1-
azabicyclo[2.2.2]octanes.
2.1. General procedure for the construction of nano magnetic catalyst
Fe3O4@O2PO2(CH2)NH3+CF3CO2
−
reported for their preparation which have desired disadvantages
[32–36]. Therefore, exploring newer and greener methods for the
synthesis of chromene-linked nicotinonitriles is highly valuable and
great demand.
Fe3O4 nanoparticles were prepared according to the previously re-
ported method [54] Then, alike to previously reported method [55],
Fe3O4@O2PO2(CH2)2NH2 were synthesized. In the next step, the re-
sulting Fe3O4@O2PO2(CH2)2NH2 in 20 mL toluene was sonicated for
15 min. Then CF3CO2H (10 mmol, 1.14 g) was added to the above
Researches in recent years have demonstrated that the concept of
anometic effect is not restricted to chemistry of carbohydrate com-
pounds and its role is observed in various chemical phenomena
[37–44]. One of the most important features of anometic effect is the
interference in bond-weakening and unusual hydride transfer processes.
This effect obviously observed in the reaction mechanism of Cannizzaro
reaction and as well as in the case of tricyclic orthoamides [45]. Rapid
solvolysis and fragmentation of 4-halo-1-azabicyclo[2.2.2]octanes de-
monstrated that if the steric arrangement is correct, the bond-weak-
ening effect can be happened through a σ-bond framework. In the case
of this compound, the overlap between nitrogen lone pair electrons
leads to broken of CeC and CeX bonds respectively (Scheme 1) [46].
Thus the major factor for mentioned fragmentation is anomeric effect
and/or negative hyperconjugation. Recently, anomeric based oxidation
has been reviewed [47].
mentioned mixture and refluxed for 12 h to give desired catalyst
Fe3O4@O2PO2(CH2)2NH3+CF3CO2
.
−
2.2. General procedure for the synthesis of 3-acetylcoumarin derivatives
According to the previously reported procedure [32–36], in a round
bottom flask, a mixture of 2-hydroxy benzaldehyde or 2-hydroxy-3-
methoxy benzaldehyde (20 mmol), ethyl acetoacetate (20 mmol, 2.6 g)
and dimethylamine (0.5 mL) in 10 mL distilled water was stirred at
room temperature until yellow precipitate was formed. After that, the
precipitate filtered off and washed thoroughly with ethanol to give pure
3-acetylcoumarin derivatives.
In this study, in connection with our previous investigation for the
synthesis of biological valuable heterocyclic structures and developing
our recently established term entitled "anomeric based oxidation" as a
new mechanistic lookout for the oxidative aromatization of a good
range of susceptible heterocyclic molecules [45,47], herein, we wish to
report a novel functionalized magnetic nanoparticle as an efficient and
recoverable catalyst for facile preparation of 2-amino-6-(2-oxo-2H-
chromen-3-yl)-4-arylnicotinonitrile derivatives via vinylogous anomeric
based oxidation mechanism (Schemes 2 and 3).
2.3. General procedure for the synthesis of 2-amino-6-(2-oxo-2H-chromen-
3-yl)-4-arylnicotinonitrile derivatives
To the mixture of aromatic aldehydes (1 mmol), 3-acetylcoumarin
derivatives (1 mmol), malononitile (1 mmol, 0.066 g), and ammonium
acetate (1.5 mmol, 0.116 g) in
a round bottom flask, Fe3O4@
−
O2PO2(CH2)2NH3+CF3CO2 (10 mg) was added as a catalyst and the
resulting mixture was stirred magnetically under solvent-free condi-
tions at 70 °C in an oil bath for the suitable time (Table 2). After
completion of the reaction, as checked out using TLC (n-hexane/ethyl
acetate (2:1)), hot ethyl acetate was added to the reaction mixture for
precipitation of nanomagnetic catalyst and dissolving the desired pro-
duct and unreacted starting materials. Afterwards, Fe3O4@
The systematic development of vinylogous anomeric based oxida-
tion on the suitable molecules, allows the design of synthetic meth-
odologies based on anomerically driven stereoselective reactions, or
highly biased equilibria among stereoisomers (Scheme 4). Scheme 4
shows that a paramount preference for a reaction which benefits from
two lone pairs antiperiplanar to the leaving group, leading to breaking
of the endocyclic CeN bond. The other products would derive from a
leaving group departure that involves only one lone pair that is anti-
periplanar to the departing group. The similar effects have been re-
ported for an enzymatic reaction (Scheme 5).
−
O2PO2(CH2)2NH3+CF3CO2 was separated from the reaction mixture
by using an external magnetic bar. After evaporation of the ethyl
acetate, EtOH was added to the mixture for precipitation of the desired
products. Finally, recrystallization of the obtained precipitate yielded
the pure products.
In the many biological transformations involve oxidation and/or
reduction of substrates by NADP+/NADPH or NAD+/NADH systems,
the unusual hydride transfer from carbon atom via a vinylogous
anomeric based oxidation (ABO) is the major step in the oxidation-re-
duction mechanism (Scheme 6). Thus systematic investigation of ABO
2.4. Selected spectral data
2.4.1. 3-Acetyl-2H-chromen-2-one
Melting point: 119–121 °C.
FT-IR (KBr): ν (cm−1): 3052, 1724, 1686, 1601, 1557.
+
−
Scheme 2. The synthetic pathway for the preparation of Fe3O4@O2PO2(CH2)2NH3 CF3CO2
.
21

F. Karimi et al.
MolecularCatalysis463(2019)20–29
Scheme 3. Synthesis of 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitrile derivatives in the presence
a
catalytic amount of Fe3O4@
−
O2PO2(CH2)2NH3+CF3CO2
.
Scheme 4. Breaking of the endocyclic CeN bond due to the anomeric effect [48].
FT-IR (KBr): ν (cm−1): 3079, 1735, 1685, 1601, 1473.
δH (300 MHz, DMSO): 8.62 (s, 1H, Coumarin 4-H), 7.49–7.34 (m,
3H, ArH), 3.94 (s, 3H, OMe), 2.60 (s, 3H, COMe).
δC (75 MHz, DMSO): 195.6, 158.6, 147.7, 146.7, 144.4, 125.3,
125.0, 122.1, 119.1, 116.9, 56.7, 30.5.
2.4.3. 2-Amino-4-(4-chlorophenyl)-6-(2-oxo-2H-chromen-3-yl)
nicotinonitrile (1b)
Melting point: 243–245 °C.
FT-IR (KBr): ν (cm−1): 3470, 3312, 2205, 1732.
δH (300 MHz, DMSO): 8.85 (s, 1H, Coumarin 4-H), 7.91–7.89 (d,
J = 6 Hz, 1H, ArH), 7.75–7.66 (m, 5H, ArH and PyrH), 7.56–7.42 (m,
3H, ArH), 7.13 (s, 2H, NH2).
Scheme 5. Anomeric effect in an enzymatic reaction [49].
δC (75 MHz, DMSO): 160.7, 159.5, 154.1, 154.0, 153.9, 144.3,
136.2, 135.2, 133.7, 130.5, 130.0, 129.5, 125.5, 124.7, 124.1, 119.3,
117.7, 116.9, 116.5, 112.8, 88.6.
2.4.4. 2-Amino-4-(3,5-difluorophenyl)-6-(2-oxo-2H-chromen-3-yl)
nicotinonitrile (1o)
Melting point: 269–271 °C.
FT-IR (KBr): ν (cm−1): 3408, 3320, 2206, 1729.
δH (300 MHz, DMSO): 8.85 (s, 1H, Coumarin 4-H), 7.93- 7.91 (d,
J = 6 Hz, 1H, ArH), 7.74–7.71 (m, 1H, ArH), 7.65 (s, 1H, Pyr-H),
7.54–7.41 (m, 5H, ArH), 7.22 (s, 2H, NH2).
Scheme 6. Molecular structures of NADH and NADPH [50–53].
δC (75 MHz, DMSO): 162.8 (d, J = 232.5 Hz), 160.6, 159.5, 154.2,
154.1, 152.7, 147.7, 144.5, 140.8 (d, J = 10.5 Hz), 133.8, 130.1, 125.5,
124.1, 119.3, 116.6, 112.6 (d, J = 16.5 Hz), 112.2, 106.6 (t,
J = 25.5 Hz), 88.7.
δH (300 MHz, DMSO): 8.64 (s, 1H, Coumarin 4-H), 7.96–7.92 (m,
1H, ArH), 7.77–7.71 (m, 1H, ArH), 7.46–7.38 (m, 2H, ArH), 2.59 (s, 3H,
COMe).
δC (75 MHz, DMSO): 195.5, 158.9, 155.1, 147.5, 134.9, 131.2,
125.4, 124.8, 118.6, 116.6, 30.5.
2.4.5. 2-Amino-6-(8-methoxy-2-oxo-2H-chromen-3-yl)-4-(4-
(trifluoromethyl)phenyl) nicotinonitrile (1p)
Melting point: 288–290 °C.
2.4.2. 3-Acetyl-8-methoxy-2H-chromen-2-one
FT-IR (KBr): ν (cm−1): 3458, 3359, 2213, 1726.
δH (300 MHz, DMSO): 8.84 (s, 1H, Coumarin 4-H), 7.99–7.97 (d,
Melting point: 170–172 °C.
22

F. Karimi et al.
MolecularCatalysis463(2019)20–29
Fig. 1. FT-IR spectrum of the new nano magnetic heterogeneous catalyst.
Fig. 2. EDX analysis of the novel catalyst.
Fig. 3. SEM images of the novel nanomagnetic catalyst.
J = 6 Hz 2H, ArH), 7.88–7.85 (d, J = 6 Hz 2H, ArH), 7.69 (s, 1H, Pyr-
H), 7.45-7.35(m, 3H, ArH), 7.22 (s, 2H, NH2), 3.96 (s, 3H, OMe).
δC (75 MHz, DMSO): 160.7, 159.2, 154.1, 153.8, 146.8, 144.6,
143.4, 141.4, 129.7, 126.3 (q, J = 4.5 Hz), 125.4, 124.1, 121.1, 119.8,
116.8, 115.8, 112.8, 101.3, 88.6, 56.7.
3. Result and discussion
Development of reusable catalysts and their application in the
synthesis of target drug candidates are our main interest [56]. With this
aim, Fe3O4@O2PO2(CH2)2NH3+CF3CO2 was designed, synthesized,
−
characterized, and applied for synthesis of a good range of 2-amino-6-
(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitriles. The described reusable
nanomagnetic
heterogeneous
catalyst,
namely
Fe3O4@
23

F. Karimi et al.
MolecularCatalysis463(2019)20–29
Fig. 4. TEM images of new nanomagnetic catalyst.
Fig. 5. VSM hysteresis curve of a, b and desired catalyst c.
Fig. 6. TGA and DTG curves of the nanomagnetic catalyst.
−
O2PO2(CH2)2NH3+CF3CO2 was synthesized as depicted in Scheme 2.
As mentioned above, we probed its catalytic applicability at the for-
mation of 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitrile
derivatives via the reaction of various aromatic aldehydes, 3-
acetylcoumarin derivatives, malononitrile, and ammonium acetate,
under solvent‐free conditions (Scheme 3). It is worthy to mention that
3-acetylcoumarin derivatives were synthesized from the reaction of
salicylaldehyde and ethyl acetoacetate in the presence of
24

F. Karimi et al.
MolecularCatalysis463(2019)20–29
Table 1
Fe3O4 nanoparticles with 2-aminoethyl dihydrogen phosphate and
CF3CO2H respectively during the preparation of the catalyst.
TGA/DTG analysis was applied to study the thermal stability of
Optimizing of the reaction conditions for the synthesis of 2-amino-6-(2-oxo-2H-
chromen-3-yl)-4-arylnicotinonitrile derivatives.a
Entry Solvent
−
Fe3O4@O2PO2(CH2)2NH3+CF3CO2 and the obtained curves is illu-
Temperature (°C) Load of catalyst
(mg)
Time
Yield (%)b
(min)
strated in Fig. 6. The weight loss upon heating from room temperature
to about 160 °C can be attributed to the evaporation of water or other
organic solvents which were employed during the course of catalyst
preparation (weight loss of about 3%). Also, the weight loss from 160 to
360 °C can be ascribed to the decomposition of the ionic tags loaded on
catalyst (weight loss of about 9.34%). The weight loss from 360 to
590 °C, can be related to decomposition of organic layer connected to
Fe3O4 nanoparticles (weight loss of about 7%). Based on obtained re-
sults, the presented nanomagnetic catalyst shows proper thermal be-
havior upon the investigated reaction.
1
–
r.t.
10
10
10
10
15
5
180
60
60
2
50
75
3c
4
–
70
45
83
–
90
45
85
5
–
70
45
85
6
–
70
60
70
7
–
70
–
180
60
25
8d
9e
10
11
12
13
14
15
–
70
10
10
10
10
10
10
10
10
40
–
70
60
45
H₂O
C₂H₅OH
CH₃CN
EtOAc
CH2Cl2
70
180
180
180
180
180
180
40
70
35
Reflux
Reflux
Reflux
30
3.2. Application of the nanocatalyst in the synthesis of 2-amino-6-(2-oxo-
2H-chromen-3-yl)-4-phenylnicotinonitrils
35
Trace
Trace
n-Hexane Reflux
After
characterizing,
the
role
of
Fe3O4@
a
O2PO2(CH2)2NH3+CF3CO2− as a heterogeneous nanomagnetic catalyst
was evaluated at the synthesis of 2-amino-6-(2-oxo-2H-chromen-3-yl)-
4-phenylnicotinonitrils. In attempting to test its catalytic performance
and in order to find the best operational reaction conditions in terms of
amount of nanomagnetic catalyst, solvent and temperature, benzalde-
hyde, 3-acetylcoumarin, malononitrile, and ammonium acetate were
picked up as model substrates. As revealed in Table 1, the best results
were achieved when the reaction was performed using 10 mg of na-
nomagnetic catalyst at 70 °C and under solvent free conditions (Table 1,
entry 3). Also, we investigated the optimal reaction conditions under
nitrogen and argon atmosphere to present an evidence for the final step
of the suggested anomeric based oxidation mechanism for aromatiza-
tion of target molecules. The obtained results showed that the yield and
time for two reactions under air, nitrogen, and argon atmosphere are
same. To optimize the reaction temperature, the model reaction was
performed at ambient temperature, 50 °C, 70 °C and 90 °C. As reveled in
Table 1, 70 °C gives the best results and therefore it is the optimal re-
action temperature (Table 1, entry 1–4). Furthermore, the amount of
nanomagnetic catalyst was also optimized. The obtained results in-
Reaction conditions: benzaldehyde (1 mmol, 0.106 g), 3-acetylcoumarin
(1 mmol, 0.188 g), malononitrile (1 mmol, 0.066 g) and ammonium acetate
(1.5 mmol, 0.115 g).
b
c
Isolated yields.
Data for the model reaction under air, nitrogen and argon atmosphere are
similar.
d
Reaction performed using Fe3O4 nanoparticles as a catalyst.
e
Reaction performed using Fe3O4@O2PO2(CH2)2NH2 nanoparticles as a
catalyst.
dimethylamine in water.
3.1. Characterization of novel nanomagnetic catalyst
The structure of Fe3O4@O2PO2(CH2)2NH3+CF3CO2 was con-
−
firmed using suitable techniques such as FT‐IR, EDX, SEM, TEM, TG,
DTG, and VSM. Details are discussed below.
The FT-IR spectrum of the novel ionically tagged nanomagnetic
heterogeneous catalyst "Fe3O4@O2PO2(CH2)2NH3+CF3CO2−" was in-
vestigated in the domain of 400–4000 cm−1 (Fig. 1). The broad peak at
about 2600–3600 cm−1 is related to ammonium moiety of the novel
catalyst, uncoated OH groups on to the surface of Fe3O4 and physically
absorbed water during the catalyst preparation. Also, the carbonyl
group within the structure of the prepared catalyst appeared at
−
dicated that 10 mg of Fe3O4@O2PO2(CH2)2NH3+CF3CO2 is the opti-
mized amount of the catalyst (Table 1, entry 3). Also, we tested the
model reaction in the presence of Fe3O4 and Fe3O4@O2PO2(CH2)2NH2
but, the obtained data was not satisfactory (Table 1, entries 8 and 9).
Also, comparing the achieved results from solvent free condition and
different solvents like H2O, C2H5OH, CH3CN, CH3CO2C2H5, CH2Cl2,
and n-hexane, illustrated that the solvent free condition is the best of
choice.
1682 cm−1
1200 cm−1
.
.
P]O stretching mode is distinguishable at about
For elemental characterization of the prepared nanomagnetic cata-
lyst, energy dispersive X‐ray (EDX) analysis was applied. The data from
energy dispersive X-ray (EDX) analysis of the new heterogeneous cat-
alyst showed all expected elements including iron, oxygen, phos-
phorous, carbon, nitrogen, and fluorine atoms as indicated in Fig. 2.
For determination of the size and morphology of the novel catalyst,
SEM analysis was used. As can be concluded from Fig. 3, the catalyst
particles have a mean diameter of about 26–36 nm with nearly sphe-
rical in shape.
Subsequently of recognizing the optimal reaction parameters, to
study
the
efficacy
and
applicability
of
the
Fe3O4@
O2PO2(CH2)2NH3+CF3CO2− as a magnetic nanoparticles catalyst in the
preparation of target molecules, varied aryl aldehydes bearing electron
withdrawing and electron donating substituents were treated with 3-
acetylcoumarin derivatives, ammonium acetate, and malononitile to
furnish the corresponding 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-phe-
nylnicotinonitril derivatives with high yields and shorten reaction
times. The attained data as indexed in the Table 2 disclose that all re-
actions carried out gently under optimal reaction conditions with good
to high yields.
Also, an insight to the novel nanomagnetic catalyst was achieved by
TEM images. The recorded TEM images were illustrated in Fig. 4. Ac-
cording to the obtained TEM images, the sizes of the catalyst particles
are in the nanometer scale.
In a comparative manner VSM analysis was applied to characterize
the magnetic properties of the Fe3O4 nanoparticles (a), Fe3O4@
3.3. Catalyst recycling and reusing test
O2PO2(CH2)2NH2
(b)
and
desired
catalyst
Fe3O4@
One of the interesting features of nanomagnetic catalysts is their
simple separation from the reaction mixture by applying an external
magnet bar. The reusability test of the presented nanomagnetic catalyst
was investigated upon the condensation reaction between 4-ni-
trobenzaldehyde, malononitrile, 3-acetylcoumarin and ammonium
acetate in 60 min. As mentioned above, after completion of the
O2PO2(CH2)2NH3+CF3CO2 (c). The obtained hysteresis curves are
depicted in Fig. 5. According to the resulting hysteresis curves, the
saturation of Fe3O4@O2PO2(CH2)2NH3+CF3CO2− as a catalyst reduced
from 66.23 emu g−1 for Fe3O4 nanoparticles to 55.15 emu g−1. This
reduction in saturation arises from the surface modification of the
−
25

F. Karimi et al.
MolecularCatalysis463(2019)20–29
Table 2
− a
Synthesis of target molecules 1a-p in the presence of Fe3O4@O2PO2(CH2)2NH3+CF3CO2
.
Entry
X
Y
Product
Structure
Time (min)
45
Yield (%)b
83
Melting point (°C), [found] [Lit]·
280–282 [258–259] [32]
1
H
H
1a
2
3
4-Cl
2-Cl
H
H
1b
1c
45
60
91
87
243–245 [245–247] [33]
230–232 [287–289] [32]
4
5
4-Br
3-Br
H
H
1d
1e
45
50
88
84
285–287 [224–226] [34]
280–282 [242–244] [34]
6
7
4-NO2
3-NO2
H
H
1f
60
60
94
95
250–252 [252–254] [33]
254–256 [262–264] [32]
1g
8
9
4-CN
4-Me
H
H
1h
1i
60
60
92
75
276–278 [332–334] [36]
270–272 [271–273] [33]
(continued on next page)
26

F. Karimi et al.
MolecularCatalysis463(2019)20–29
Table 2 (continued)
Entry
10
X
Y
Product
1j
Structure
Time (min)
60
Yield (%)b
76
Melting point (°C), [found] [Lit]·
221–223 [268–270] [33]
4-OMe
H
11
12
3-OMe
H
H
1k
1l
70
75
75
78
193–195 [242–244] [36]
278–280 [278–279] [32]
3,4-OMe2
13
4-OH
H
1m
75
76
277–279 [263–264] [35]
14
15
3-OH
H
H
1n
1o
75
40
75
96
245–247 [238–240] [34]
269–271 [New]
3,5-F2
16
4-CF3
2-OMe
1p
45
93
288–290 [New]
a
b
Reaction conditions arylaldehyde (1 mmol), 3-acetylcoumarin derivatives (1 mmol), malononitrile (1 mmol, 0.066 g) and ammonium acetate (1.5 mmol, 0115 g).
Isolated yields.
reaction, hot ethyl acetate was added to the reaction mixture for pre-
cipitation of nanomagnetic catalyst and dissolving the desired product
and unreacted starting materials. Then, the catalyst was collected using
a magnet bar, washed with ethyl acetate, dried and reused for the next
runs. From the data depicted in Fig. 7, it is clear that the activity of the
investigated catalyst is restored after seven successive runs with a
marginal decreasing of its catalytic activity.
A suggested plausible mechanistic route for the synthesis of target
molecule 1a via anomeric based oxidation mechanism is demonstrated
in Scheme 7. At first, Knoevenagel condensation reaction was carried
out between activated malononitrile and benzaldehyde to gives A. The
in-situ generated ammonia from ammonium acetate, as nitrogen
source, attacks to catalytic activated 3-acethylcumarine. The reaction
Fig. 7. The reusing test of the nano magnetic catalyst.
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MolecularCatalysis463(2019)20–29
Scheme 7. Plausible mechanistic process for the synthesis of target molecule 1a via anomeric based oxidation.
Acknowledgments
was improved by imine-enamine tautomerization. The enamine A re-
acts with B through Michael condensation to gives intermediate C. After
imine to enamine tautomerization and cycloaddition, intermediate D
produced. In the next step, intermediate D through tautomerization
converted to the related intermediate E. In contrast to the previously
reported studies [34,36], that have been proposed an aerobic auto
oxidation of intermediate E to target molecule 1a, we believed that, this
step might be progress through anomeric based oxidation in the ab-
sence of oxygen molecules. In the intermediate E, sharing the electron
density from the nitrogens lone pairs to the vacant antibonding σ* or-
bital of SP3 CeH bond through vinylic C]C double bonds support the
unusual hydride transfer for releasing the molecular hydrogen (H2).
Recently, we have been named this phenomenon as an "anomeric based
oxidation" (ABO) and its development for various catalytic systems is
our main research interest [67–70]. The described "anomeric based
oxidation" (ABO) mechanism is in good agreement with the "vinylogous
anomeric effect" concept which had introduced by other researchers
[57–66]. Finally, after H2 releasing, the intermediate E converted to the
intermediate F which furnished the desired molecule 1a in the presence
of the describe nano magnetic catalyst.
We thank the Bu-Ali Sina University and Iran National Science
Foundation (INSF), Grant Number: 940124 for financial support to our
research group.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.mcat.2018.11.009.
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