CoFe2O4?SiO2-NH2-CoII NPs: An effective magnetically recoverable catalyst for Biginelli reaction

Article abstract of DOI:10.1016/j.inoche.2020.107988

Biginelli reaction entails acid-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) with simply-accessible initial substances, specifically, aldehyde, urea, and active methylene compound. DHPMs have stimulated a resurgence of attention in the previous two decades because of their broad-ranging pharmacological actions and the existence of varied all-natural products. Currently, green methods to asymmetric Biginelli reaction have been researched for anti-inflammatory DHPMs. In materials chemistry, DHPMs are increasingly decision applications in the creation of materials like polymers, adhesives, fabric dyes, etc. In light of the simplicity by which the Biginelli reaction is conducted, numerous interesting prospects expect its exploitation in variety fields. CoFe₂O₄?SiO₂-NH₂-Co^II is herein turned out to be an effective catalyst at a three-component Biginelli reaction. The yield of the corresponding DHPMs was rather large (20 cases; average 92 percent). Finally, we herein suggest a procedure that shows lots of advantages and benefits such as the whole lack of solvents, mild reaction conditions, comparatively short reaction times. Also, CoFe₂O₄?SiO₂-NH₂-Co^II NPs catalyst has been readily recovered from the reaction combination and reused, without the decrease of catalytic action.

Full text of DOI:10.1016/j.inoche.2020.107988

Journal Pre-proofs
II
CoFe O @SiO -NH -Co NPs: an effective magnetically recoverable catalyst
2
4
2
2
for Biginelli reaction
Ali Allahresani, Mehri Mohammadpour Sangani, Mohammad Ali Nasseri,
Kaveh Hemmat
PII:
S1387-7003(20)30578-5
DOI:
https://doi.org/10.1016/j.inoche.2020.107988
INOCHE 107988
Reference:
To appear in:
Inorganic Chemistry Communications
Received Date:
Revised Date:
Accepted Date:
22 February 2020
18 May 2020
21 May 2020
Please cite this article as: A. Allahresani, M. Mohammadpour Sangani, M. Ali Nasseri, K. Hemmat,
II
CoFe O @SiO -NH -Co NPs: an effective magnetically recoverable catalyst for Biginelli reaction, Inorganic
2
4
2
2
Chemistry Communications (2020), doi: https://doi.org/10.1016/j.inoche.2020.107988
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II
CoFe O @SiO -NH -Co NPs: an effective magnetically recoverable catalyst for Biginelli
2
4
2
2
reaction.
Ali Allahresani*, Mehri Mohammadpour Sangani, Mohammad Ali Nasseri, Kaveh Hemmat
Department of chemistry, Collage of Science, University of Birjand, Birjand 97175-615, Iran
E-mail: a_allahresani@birjand.ac.ir
Abstract: Biginelli reaction entails acid-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-
2
(1H)-ones (DHPMs) with simply-accessible initial substances, specifically, aldehyde, urea, and
active methylene compound. DHPMs have stimulated a resurgence of attention in the previous two
decades because of their broad-ranging pharmacological actions and the existence of varied all-
natural products. Currently, green methods to asymmetric Biginelli reaction have been researched
for anti-inflammatory DHPMs. In materials chemistry, DHPMs are increasingly decision
applications in the creation of materials like polymers, adhesives, fabric dyes, etc. In light of the
simplicity by which the Biginelli reaction is conducted, numerous interesting prospects expect its
II
exploitation in variety fields. CoFe O @SiO -NH -Co is herein turned out to be an effective
2
4
2
2
catalyst at a three-component Biginelli reaction. The yield of the corresponding DHPMs was rather
large (20 cases; average 92 percent). Finally, we herein suggest a procedure that shows lots of
advantages and benefits such as the whole lack of solvents, mild reaction conditions,
II
comparatively short reaction times. Also, CoFe O @SiO -NH -Co NPs catalyst has been readily
2
4
2
2
recovered from the reaction combination and reused, without the decrease of catalytic action.
II
Keywords: 3,4-dihydropyrimidin-2(1H)-ones, Biginelli reaction, CoFe O @SiO -NH -Co NPs,
2
4
2
2
urea, aldehyde, one-pot

1
. Introduction
More than a century ago, the Biginelli reaction is a one-pot [1], three-component condensation of
an aldehyde with -keto esters and ureas or thioureas, commonly under acidic circumstances [2].
Dihydropyrimidine derivatives provide attractive pharmacological activities attributes inclusive
antiviral, antimalarial, antihypertensive, and antibacterial properties, and different kinds of
activities [2]. The main reactions are suffered from lower yields and limited substrate range, the
developing pharmacological significance of dihydropyrimidines has led to the renewed
investigation of the reaction conditions which has revealed a variety of suitable solvents (such as
ionic liquids) and catalysts to improve the reaction [2-8]. Furthermore, the range of the Biginelli
reaction has been broadened with alcohol instead of aldehydes as well as some alternative active
hydrogen building blocks in place of β-keto esters [2-8]. Significantly, the effect of the stereogenic
center considerably affects the biological activities of dihydropyrimidines. For instance, in Fig. 1,
the R enantiomer of dihydropyrimidine, which is an antihypertensive agent, is shown to be more
effective than its S enantiomer [9]. As a result, to enhance application range and potency in drugs
getting enantioenriched materials is necessary. Over the years, some enantioselective synthetic
protocols have been expanded. For the first time, the chiral ytterbium catalyst was used as an
enantioselective catalyst for the Biginelli reaction, to afford the corresponding dihydropyrimidines
in good efficiencies with excellent enantioselectivities [10].
O
HN OC
2
N
NH
COOiPr
NO2
Fig. 1. Antihypertensive SQ 32926

In the presence of chiral amines (usually by achiral Brønsted acids as co-catalysts), pyrrolidinyl
tetrazole, iodine, chiral Brønsted acids [2,11-13] proline derivatives, chiral ionic liquids, and in
specific phosphoric acids [14-21] (and derivatives), asymmetric Biginelli reactions were then
successfully done and provided aim chiral dihydropyrimidines has been obtained to excellent
yields and enantioselectivities [17-21]. Multi-component reactions, especially the Biginelli
reactions, are a reliable tool to form complex molecules with easiness and brevity. Truly, they
allow the creation of corresponding products to be able to occur within a single operation through
three or even more reactants, with bond-forming effectiveness, high atom-economy, adaptability
with green solvents, and under mild circumstances. Therefore, they may be effectively classified
as eco-compatible and sustainable procedures [22,23]. Though, some disadvantages exist,
particularly the use of extremely toxic organic solvents, large values of catalyst, hard reaction
conditions, and difficult and time-consuming target product separation. Consequently, the
expansion of simple and environmentally friendly Biginelli procedures is in the requirement, and
newly some fascinating green protocols have already been proposed [24].
While previously highlighted, valid and attractive techniques for the synthesis of
dihydropyrimidines are generally recognized. Nevertheless, these reactions are generally done in
organic solvents; catalysts are not reused and recovered.
II
Considering this and to additionally improve the catalytic efficiency of CoFe O @SiO -NH -Co
2
4
2
2
NPs (Fig. 2) which is an effective catalyst in Biginelli reaction, we thus report our investigations
green Biginelli reactions between urea, aromatic aldehydes, and ethyl acetoacetate was done in the
presence of the corresponding catalyst (Scheme 1).

O
N
H
O
S i
CoFe O
2
4
O
NH2 CoII HN
H
N
II
Fig. 2. CoFe O @SiO -NH -Co NPs
2
4
2
2
R1
HN
O
COOR2
R
O
O
O
O
II
CoFe O @SiO -NH -Co
2
4
2
2
R
R1
OR2
0
H N
2
NH2
Solvent-free, 110 C
NH
A
B
C
D
II
Scheme 1. Biginelli reaction catalyzed by CoFe O @SiO -NH -Co NPs
2
4
2
2
2
2
. Experimental section
.1. Chemicals
Reagents and solvents were produced in Merck or Fluka chemical companies. TLC on silica-gel
polygram SILG/UV 254 plates were used to determine the purity of the products. An
Electrothermal 9100 apparatus was used to measure melting points. A Perkin Elmer 781
-1
spectrometer was used to take IR spectra in KBr pellets which were reported in cm . A Bruker
1
13
DPX-250 Avance instrument was used to measure HNMR and CNMR spectra at 250 MHz and
6
2.9 MHz in CDCl or DMSO-d . The chemical shift was given in ppm relative to TMS as the
3
6
internal standard. A Bruker D -advance X-ray diffractometer with Cu K (λ = 0.154 nm) radiation
8
α
was used to carry out power X-ray diffraction (XRD). Using vibrating sample magnetometer
VSM) leak shore 7200, the magnetic properties were determined at 300 K Vsm leak shore. MIRA
TESCAN-XMU spectrometer was used for scanning electron microscopy.
(
3

2
2
.2. Catalyst preparation
.2.1. Preparation of CoFe O magnetic nanoparticles
2
4
At first, iron (III) nitrate nonahydrate and cobalt (II) nitrate hexahydrate in a molar proportion of
:1 were dissolved and sonicated for 30 min within water (100 mL). At that point, NaOH (1M)
2
was additional to the solution and vigorous stirring continuously for 2 h at 80°C. The respective
black precipitate powder easily is separated by an external magnet and washed with DI water as
-
o
long as the OH ion free and vacuum oven drying was carried out for 10 h at 80 C [25].
2
.2.2. Preparation of CoFe O @SiO magnetic nanospheres
2 4 2
0
.15 gr of CoFe O were added to 50 mL EtOH (80 %) and dispersed under ultrasound conditions
2 4
for 30 min. Afterward, the pH of the mix should be 11–12. NH .H O solution should be added to
3
2
increase the pH of the mixture to 11-12. In the next step, 2 mL of TEOS added drop by drop into
o
the mixture with vigorous stirring at 25 C for 20 h. Then, by an external magnet, the gray powder
which was the synthesized CoFe O @SiO was separated and washed with deionized water.
2
4
2
o
Subsequently, at 80 C, CoFe O @SiO was dried for 10 h [25].
2
4
2
2
.2.3 Preparation of NH -Pr
2
A mixture of triethylenetetramine (1 mmol) and triethanolamine (2 mmol) was dissolved in 30 mL
EtOH (solution A) and 3-chloropropyltriethoxysilane (APTMS) were dissolved in 20 mL EtOH
(solution B). Afterward, for 24 hours under reflux conditions, solution B was drop by drop added
to this solution A. Eventually, remove the solvent by a rotary evaporator and precipitate the
product to give a yellow powder.
2
.2.4 Preparation of CoFe O @SiO -NH
2 4 2 2
With 20 mL dry toluene, 0.7 mL NH -Pr was dissolved (solution A). In the next step, 0.2 g
2
CoFe O @SiO was dissolved in dry toluene (30 mL) (solution B). The solution A was added drop
2
4
2
by drop into the solution B. Then, Under Ar atmosphere, the resulting mixture was stirred for 48

o
o
h at 105 C. The precipitate was washed with toluene and ethanol and at 105 C, CoFe O @SiO
2
2
4
-
NH was dried for 12 h [26].
2
II
2
.2.5 Preparation of CoFe O @SiO -NH -Co NPs
2 4 2 2
To a suspension of CoFe O @SiO -NH (1 g) in 20 mL EtOH, Co (NO ) .6H O (4.2 mmol, 0.8 g
2
4
2
2
3 2
2
in 20 ml EtOH) was added. The mixture is stirred under reflux for 25 h. By an external magnet,
II
the resulting CoFe O @SiO -NH -Co NPs product was collected and washed repeatedly with
2
4
2
2
EtOH. Then, dried beneath vacuum for 12 h at 80 ° C [27].
.2.6 General procedure for the Biginelli reaction
2
A combination of aldehyde (1 mmol), urea or thiourea (1 mmol), -keto esters (1 mmol), and
II
CoFe O @SiO -NH -Co NPs (0.01 g) was stirred by refluxing for 15 min (Scheme 1). Afterward
2
4
2
2
the end of the reaction, the combination was cooled down to ambient temperature and
II
CoFe O @SiO -NH -Co was collected via an external magnet. The reaction mix was crystallized
2
4
2
2
using ethanol [28].
Selected spectral data
Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(compound 1, Table 4): Solid, mp 202-204 °C, IR (KBr): 3416, 3232, 3107, 2935, 1701, 1648,
-1 1
1
598 cm , H NMR (DMSO-d ):  = 9.17 (s, 1 H), 7.72 (s, 1 H), 7.21–7.32 (m, 5 H), 5.14 (s, 1
6
1
3
H), 3.98 (q, J = 7.2 Hz, 2 H), 2.24 (s, 3 H), 1.08 (t, J = 7.2 Hz, 3 H), C NMR (DMSO-d ):  =
6
1
65.4, 152.2, 148.4, 144.9, 128.4, 127.3, 126.3, 99.3, 59.2, 54.0, 17.8, 14.1
Methyl 4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(compound 12, Table 4): Solid, mp 204-206 °C, IR (KBr): 3366, 3219, 3105, 2945, 1711, 1635,
-1 1
1
496 cm , H NMR (DMSO-d ):  = 9.21 (s, 1 H), 7.76 (s, 1 H), 7.31 (t, J = 8.4 Hz, 5 H), 5.44 (s,
6

1
3
1
1
H), 5.16 (s, J = 2.8 Hz, 1 H), 4.01 (q, 2 H), 1.11 (t, 3 H), C NMR (DMSO-d ):  = 165.81,
6
52.62, 148.83, 145.34, 128.86, 127.74, 126.72, 99.73, 59.66, 54.43, 18.25, 14.54.
3
. Results and discussion
FT-IR analysis
Fourier transform infrared (FT-IR) spectroscopy indications the adjustment of CoFe O NPs (a),
2
4
II
CoFe O @SiO NPs (b), Pr-NH (c), CoFe O @SiO -NH NPs(d), CoFe O @SiO -NH -Co NPs
2
4
2
2
2
4
2
2
2
4
2
2
-1
(
e). As appeared in Fig. 3a frequency 3398cm O-H stretching by the hydroxyl groups attached to
the surface of the cobalt oxide and showed that water molecules chemically adsorbed by the
-1
surface of the metal during the synthesis process. Furthermore, the frequency at 588cm is the
-1
presence of an oxygen metal bond. The frequency at 1623 cm is due to O-H in-plane and out of
plane bending mode. The presence of water adsorption bonds, in and out of plane and oxygen
metal bonds approves the existence of Co in the samples synthesized. Fig. 3b adsorption broadband
-1
at 1097 cm is associated with Si-O. TETA grafted existence can be confirmed by the appearance
-1
of three different absorption bands at 2914, 1945, and 1456 cm which can be attributed to the
N-H bending vibrations (primary and secondary amines) (Fig. 3d). Besides, the vibration band for
-1
binding N-H stretching (3500-3000 cm ) cannot be defined with precision, due to overlap with
II
the broad absorption band of OH…OH, bond. When Co coordination, the intensity of the bending
vibration characteristic absorption band related to N-H was considerably decreased (Fig. 3e)

(a)
9
27.11
1
623.29
588.02
99.51
3
398.44
(b)
7
1
100.46
4
69.58
(c)
1
645.66
2
914.62
1
037.91
3
344.12
1
456.97
(d)
1
355.87
(e)
4
000
3500
3000
2500
2000
1500
1000
500
Wavenumbers (cm-1)
Fig. 3. FT-IR spectra of CoFe O NPs (a), CoFe O @SiO NPs (b), Pr-NH (c), CoFe O @SiO -NH
2
2
4
2
4
2
2
2
4
2
II
NPs(d), CoFe O @SiO -NH -Co NPs (e)
2
4
2
2
XRD analysis
Diffraction spectra X-ray uncoated particles and coated with the dispersion and the silica agents
are shown in Fig. 4. From Fig. 4, it is clear that the synthesized nanoparticles CoFe O using the
2
4
decomposition method are characteristic of the cubic spinel phase corresponding to CoFe O
2
4
(JCPDS 22-1086). In Fig. (4) a wideband appears in each observation spectrum. This is usually
typical of amorphous components and crystalline materials regarding ultrasmall wherein the
diffraction peaks cannot be properly resolved.
It is reported that the amorphous SiO affects the microstructure of composite materials
2
significantly and gradually decreases with the increasing concentration of SiO . Overall, the
2
growth of grain ferrites may be influenced in the presence of pores or inclusions in the grain
boundaries. Diffraction patterns distinctive X-ray at 2θ = 18.1°, 20.9°, 30.2°, 35.5°, 43.3°, 57.2 °,

II
6
2.8° and 74.6° of CoFe O @ SiO -NH Co NPs identified by an evaluation data literature and
2 4 2 2
confirm the particles are polycrystalline structure.
(a)
(b)
10
20
30
40
50
60
70
80
90
2
θ/( ͦ)
II
Fig. 4. XRD pattern of CoFe O (a), and CoFe O @ SiO -NH Co (b)
2
4
2
4
2
2
TEM analysis
II
According to the TEM images, the average size CoFe O @ SiO -NH Co magnetic nanoparticles
2
4
2
2
are approximately 20-90 nm (Fig. 5). Although the size of CoFe O nanoparticles is about 2-6 nm.
2
4
The TEM image shows the successful coating of the silica layer around the magnetic core.
II
Fig. 5. TEM images of CoFe O (a) CoFe O @ SiO -NH Co (b)
2
4
2
4
2
2

EDX analysis
EDX spectrum of CoFe O @ SiO -NH Co , which is shown in Fig. 6, clearly reveals the presence
II
2
4
2
2
of all the major elements of the expected (Fe, Co, Si, N, C) consisting of a composite of these three
components.
II
Fig. 6. EDX spectrum of CoFe O @ SiO -NH Co
2
4
2
2
VSM analysis
The magnetization curves of CoFe O NPs and silica-coated CoFe O nanocomposites, and
2
4
2
4
II
o
CoFe O @ SiO -NH Co at 25 C demonstrate in Fig. 7. According to Fig. 7(a), the saturation
2
4
2
2
magnetization of CoFe O NPs was 39.92 emu/g. Additionally, Fig. 7 (b,c) demonstrates the
2
4
magnetization curves of silica-coated of CoFe O nanocomposite and silica-coated of CoFe O
4
2
4
2
II
nanocomposite with diverse dispersing agents, for example, NH and Co (in CoFe O @ SiO -
2
2
4
2
II
NH Co ). The saturation magnetization values for all these nanoparticles are 28.92, and 6.25
2
emu/g respectively. These results reveal a large decline in the saturation magnetization of this
CoFe O @SiO nanocomposite in comparison with the CoFe O NPs. We can see in Fig. 4
4
2
2
2
4
variations in the magnetic attributes of the nanocomposites in effect the surface modification with
the dispersing agents. It has been reported [29] that the magnetic behavior of the system due to the

presence of the dispersing agent on the surface of the NPs, can change the surface anisotropy and
the magnetic moment. The magnetic characteristics of nanoparticles are a mixture of several
anisotropy mechanisms, such as surface anisotropy, magnetocrystalline anisotropy, and
interparticle interactions, coating ferrite NPs by silica will probably influence interparticle
interactions into the net anisotropy and the participation of the surface anisotropy [30].
II
Fig. 7. VSM spectrum of CoFe O NPs, CoFe O @SiO NPs, CoFe O @SiO -NH -Co NPs
2
4
2
4
2
2
4
2
2
3
.5. Reaction optimization
II
In the presence of a catalytic amount of CoFe O @SiO -NH -Co under varying circumstances,
2
4
2
2
the model reaction among ethyl acetoacetate, urea, and benzaldehyde was initially investigated for
the synthesis of dihydropyrimidines. As mentioned in Table 1, under neat conditions, under
heating at 110°C and in the presence of 0.01 g of catalyst, the best result was obtained, which gave
the corresponding product in excellent yield.
The amount of catalyst was also changed. Table 1 summarizes the results. The results presented
that the reaction of the catalyst concentration affects performance crucial. Under the same

conditions, reducing the catalyst concentration afforded lower yields result. The product decreased
significantly with increasing catalyst concentration (more 0.01g). Consequently, because the
reaction is completed within high performance, this condensation is better catalyzed by 0.01 g of
II
CoFe O @ SiO -NH Co NPs. This product decreased significantly with increasing catalyst
2
4
2
2
concentration (over 0.01 g). As a result, because the reaction is finished in high yield, it's the best
II
condensation catalyzed by 0.01 g CoFe O @ SiO -NH -Co NP.
2
4
2
2
II
a
Table 1. Optimization of various amounts of CoFe O @SiO -NH -Co for the model reaction
.
2
4
2
2
Entry
Catalyst (mg)
Temperature
℃)
Time (min)
Yield (%)
(
1
2
3
4
10
50
110
110
110
110
15
15
15
15
96
96
70
97
0
Trace
5
6
7
CoFe O
110
110
110
15
15
15
15
18
20
2
4
CoFe O @SiO
2
2
4
CoFe O @SiO NH
2
2
4
2-
o
Reaction conditions: benzaldehyde (1 mmol), urea (1 mmol), ethyl acetoacetate (1 mmol), 110 C,
solvent free.
The reaction was studied in diverse solvents (Table 2). The results showed that the reaction
efficiency is influenced by different solvents. Low yield (10-68%) was obtained by acetonitrile,
water, ethanol, and n-hexane while the results can be enhanced in the absence of solvent (solvent-
free). As a result, 96% of the yield was obtained in the solvent-free.

Table 2. Optimization of various solvent condition for the model reactiona.
Entry
Solvent
Temperature
℃)
Time (min)
Yield* (%)
(
1
2
3
4
5
Solvent-free
n-Hexane
110
15
96
10
37
20
68
Reflux
Reflux
Reflux
Reflux
360
360
360
360
CH CN
3
H O
2
EtOH
DCM
6
7
Reflux
Reflux
360
360
15
55
o
EtOH/H O
2
Reaction conditions: benzaldehyde (1 mmol), urea (1 mmol), ethyl acetoacetate (1 mmol), 110 C, 0.01
g of CoFe O @SiO -NH -Co .
II
2
4
2
2
By carrying out the model reaction at different temperatures, the effect of the temperature of the
o
reaction was studied. The best result was obtained within 110 C (Table 3).
Table 3. Optimization of various temperature for the model reactiona.
Entry
Temperature (oC)
Yield (%)
1
2
3
4
25
50
15
34
72
96
80
110
Reaction conditions: benzaldehyde (1 mmol), urea (1 mmol), ethyl acetoacetate (1 mmol), solvent free,
II
0
.01 g of CoFe O @SiO -NH -Co .
2 4 2 2
To additional use the scope of this reaction was carried out the reactions of diversely substituted
aldehydes, -keto esters, carrying either electron-withdrawing or electron-donating groups with
urea. Good results are obtained from the target products irrespective of electronic substituent
effects (Table 4). Table 4 summarizes the results. In all cases, pay by dihydropyrimidines in good
to excellent results (86-98%), the reaction takes place easily.

II
Table 4. Synthesis of novel functionalized biginelli reaction derivatives by CoFe O @SiO -NH -Co
2
4
2
2
a
catalyst
.
*
Entry
A
B
Product (D)
Time(min) Yield (%)
O
O
O
1
EtOOC
15
96
NH
Me
OEt
N
H
O
NO2
O
O
O
2
15
98
EtOOC
EtOOC
EtOOC
O N
Me
OEt
2
NH
N
H
O
Cl
O
O
O
3
4
15
15
95
94
Cl
Me
OEt
NH
N
H
O
CH3
O
O
O
H C
3
Me
OEt
NH
N
H
O
OCH3
O
O
O
5
18
95
EtOOC
H CO
3
Me
OEt
NH
N
O
H

Countinued Table 4.
Entry
*
A
B
Product (D)
Time(min) Yield (%)
OH
O
O
O
6
20
90
EtOOC
HO
Me
OEt
NH
N
O
H
NO2
O
O
O
7
15
95
EtOOC
NH
Me
OEt
NO2
N
O
H
NO2
NH
O
O
O
8
9
EtOOC
15
20
94
88
NO2
Me
OEt
N
O
H
OH
NH
O
O
O
EtOOC
Me
OEt
OH
N
O
H
OMe
NH
O
O
O
1
0
EtOOC
18
92
OMe
Me
OEt
N
O
H

Countinued Table 4.
Entry
*
A
B
Product (D)
Time(min) Yield (%)
NO2
O
O
O
1
1
25
95
MeOOC
O N
2
Me
OMe
NH
N
H
O
Cl
O
O
O
1
2
25
93
MeOOC
Cl
Me
OMe
NH
O
N
H
CH3
O
O
O
1
1
1
3
4
5
30
30
35
90
89
87
H C
Me
Me
Me
OMe
OMe
OMe
MeOOC
MeOOC
MeOOC
3
NH
O
N
H
OCH3
O
O
O
H CO
3
NH
N
H
O
OH
O
O
O
HO
NH
N
O
H

Countinued Table 4.
Entry
*
A
B
Product (D)
Time(min) Yield (%)
NO2
O
O
O
1
6
20
93
MeOOC
NH
Me
OMe
NO2
N
O
H
NO2
NH
O
O
O
1
1
7
8
MeOOC
20
35
92
86
NO2
Me
Me
Me
Me
OMe
OMe
OMe
OMe
N
O
H
OH
O
O
O
MeOOC
NH
OH
N
O
H
OMe
O
O
O
1
2
9
0
MeOOC
30
20
88
90
NH
OMe
N
O
H
Br
NH
O
O
O
MeOOC
Br
N
O
H
Compared with most of the work reported, this catalyst illustrations excellent catalytic activity and
good results (96%) in a shorter time (see Table 5).

II
Table 5. Comparison of results utilizing CoFe O @SiO -NH -Co with diverse catalysts
2
4
2
2
Time Yield
Entry
Catalyst
Solvent
Condition
ref
b
(h)
(%)
90
79
95
80
95
98
90
80
1
2
3
4
5
6
7
8
ZrCl4
C H OH
reflux
100
80
4
29
30
31
32
33
34
35
36
2
5
Cu(NH SO )
CH COOH
5
2
3 2
3
Ag PW O
EtOH
3
3
12 40
H PMo O
CH COOH
reflux
45
5
3
12 40
3
Fluoroboric acid
Neat
EtOH
Neat
Neat
0.5
2
CaF2
45
Chloroferrate(III)Ionic Liquid
90
2
Triethyl ammonium tetrafluoroborate
145
1
This
work
II
9
CoFe O @SiO -NH -Co
Solvent-free
110
0.25
96
2
4
2
2
2
+
In the suggested mechanism, the first step involves the imine formation (A). Co in coordination
with imine nitrogen atom to give an intermediate (B), which activates the C=N toward nucleophilic
attack. Also, the complexation-ketoester with Co2+ enhances the nucleophilicity of -carbon-
enolate, which simplify the attack of carbon imine and amide group free of attack of carbonyl
carbon outcomes in the formation of heterocyclic six-membered intermediate (C) which, as shown
in scheme 2 by dehydration give desired DHPMs (D) [37].

O
ArCHO +
H N
NH2
2
O
HN
NH
H O
2
and H O
H N
2
2
Ar
O
CoII
N
COOEt
CoFe2O4
Ar
D
A
O
H N
2
O
HN
NH
N
OH
Ar
Ar
CoII
H
COOEt
B
C
CoFe2O4
O
O
Ar
O
CoFe2O4
EtO
N
NH2
H
CoII
O
O
OEt
O
N
H
O
S i
CoFe2O4
CoII
O
=
CoFe2O4
NH2 CoII HN
H
N
II
Scheme 2. Biginelli reaction mechanism catalyzed by CoFe O @SiO -NH -Co
2
4
2
2
The catalyst may be recovered using an external magnet at the end of the reaction. Ethanol is
utilized to wash the catalyst recycle which is then subjected to a next reaction process. The results
of the performance of the product is only slightly reduced after six runs (Fig. 8).

II
Fig. 8. Recyclability of CoFe O @SiO -NH -Co NPs in the Biginelli reaction
2
4
2
2
Conclusions
II
In conclusion, using CoFe O @SiO -NH -Co , a facile methodology was developed to prepare
2
4
2
2
3
,4-dihydropyrimidin-2(1H)-ones derivatives nanoparticles as an efficient heterogeneous catalyst.
o
At 110 C, the catalyst represents an outstanding activity in solvent-free conditions. For a wide
variety of substrates, a good to high yield of products was obtained within short reaction times.
FT-IR, SEM, VSM, and XRD analyses were used to characterize the catalyst. With the negligible
loss of efficiency, the catalyst was recycled for at least five consecutive runs. The advantages of
the catalyst include the performance, preparation from cheap and accessible materials,
environmentally benign nature, and cost-effectiveness. These advantages make it a suitable
alternative for the preparation of 3,4-dihydropyrimidin-2(1H)-ones. Moreover, separation and
recovery of the catalyst for another catalytic recycling are easy.
Acknowledgments
We gratefully acknowledge the support of this work by the University of Birjand.

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Author Biography:
Ali Allahresani, Department of chemistry, University of Birjand, Birjand, Iran

Graphical Abstract
O
R
O
2
H N
NH2
O
R
EtO
NH
O
O
R1
OEt
R1
N
O
H
Biginelli reactions
Yields (86-98%)
O
N
O
S i
H
COFe2O4
O
NH2 COII HN
H
N
Catalyst

Highlights


The reused several times without significant loss of reactivity.
II
CoFe O @SiO -NH -Co NPs: an effective magnetically recoverable catalyst for
2
4
2
2
Biginelli reaction.presented excellent efficiency.

Concise reaction time and excellent yields of products.

II
CoFe O @SiO -NH -Co NPs: an effective magnetically recoverable catalyst for Biginelli
2
4
2
2
reaction.
Ali Allahresani*, Mehri Mohammadpour Sangani, Mohammad Ali Nasseri, Kaveh Hemmat
Department of chemistry, Collage of Science, University of Birjand, Birjand 97175-615, Iran
E-mail: a_allahresani@birjand.ac.ir
Conflict of interest:
The authors declare that there is no conflict of interest.