A Br?nsted acidic ionic liquid anchored to magnetite nanoparticles as a novel recoverable heterogeneous catalyst for the Biginelli reaction

Article abstract of DOI:10.1039/d0ra09929e

In this study, simple and effective methods were used for the preparation of an ionic liquid that immobilized magnetite nanoparticles. Fe₃O₄nanoparticles were preparedviaa chemical co-precipitation method. Then, a SiO₂shel

Full text of DOI:10.1039/d0ra09929e

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A Brønsted acidic ionic liquid anchored to
magnetite nanoparticles as a novel recoverable
Cite this: RSC Adv., 2021, 11, 7271
heterogeneous catalyst for the Biginelli reaction†
Hourieh Sadat Oboudatian,
Hossein Naeimi
and Mohsen Moradian
*
In this study, simple and effective methods were used for the preparation of an ionic liquid that immobilized
magnetite nanoparticles. Fe nanoparticles were prepared via a chemical co-precipitation method. Then,
SiO shell was coated on the magnetic core via the Stober method. Finally, CPTES
chloropropyltriethoxysilane) and morpholine were coated on the SiO shell. Morpholine sulfate, an
3
O
4
a
2
(
2
acidic ionic liquid, was successfully bound to magnetite nanoparticles (Mag@Morph-AIL) and this was
used as an efficient catalyst for the preparation of 3,4-dihydropyrimidinones. Compared to previous
works, the easy separation of the nanocatalyst using an external magnet and the recyclability, non-
toxicity, versatility, and high stability of the catalyst, combined with low reaction times and excellent
yields, make the present protocol very useful for the synthesis of the title products. The synthesized
Received 23rd November 2020
Accepted 27th January 2021
DOI: 10.1039/d0ra09929e
1
13
products and catalyst were confirmed via H-NMR, C-NMR, FT-IR, scanning electron microscope, X-
ray diffraction, and elemental analysis.
rsc.li/rsc-advances
27
28
nanoparticles; magnetic nanoparticles; metal oxides; and
Introduction
enzymes. Also, this reaction can be modied using microwave
29,30
31
32–34
Dihydropyrimidinone and its derivatives have attracted signi- irradiation,
cant attention because of their potential activities as calcium organocatalysis, or using a combination of these.
channel modulators, antihypertensive agents, and antagonists
However, despite their potential utility, many of these re-
agents for neuropeptide Y (NPY) and a-1a-adrenergic recep- ported one-pot protocols suffer from shortcomings, such as the
ultrasound irradiation, ionic liquids,
35
and
1
–3
tors. Moreover, these compounds are bio-isosteres of dihy- use of expensive reagents, long reaction times, low yields, and
dropyridines, which have attracted widespread attention volatile strongly acidic conditions. Therefore, the introduction
because of their vital pharmaceutical and therapeutic proper- of milder and more efficient methods with higher yields is
4
5
6
ties, for example, anticancer, antifungal, anti-inammatory,
needed. We have investigated the synthesis of 3,4-dihydropyr-
anti- imidinone derivatives utilizing Fe @SiO nanoparticles as
7
8
9
10
antibacterial, antiviral, antidiabetic, antithyroid,
3
O
4
2
11
8
muscarinic, and hypolipidemic activities. Besides, various recyclable catalysts and eco-friendly materials, based on the
alkaloids including the dihydropyrimidine moiety have been principles of green chemistry and with the aim of developing an
isolated from natural and marine sources, and they also display ideal synthesis approach. Magnetic iron oxide nanoparticles
interesting biological properties. Hence, the synthesis of have attracted much research interest in recent years because of
a variety of these molecules is desirable and of much current their unique physicochemical properties and great potential for
12
importance.
various biomedical applications.
The synthesis of 3,4-dihydropyrimidinone compounds can
The reactivity of catalytic nanoparticles is largely determined
be performed under different conditions, including under by the energy of surface atoms, which can be easily gauged
1
3–16
strongly acidic conditions in a protic solvent.
ally been catalysed using strong Brønsted acids; Lewis acids;
homogeneous acid catalysts, such as polyphosphate esters,
It has tradition- based on the number of neighboring atoms, the bonding modes,
17–21
and the accompanying energies of the small molecules to be
22
36,37
transformed on the surfaces of nanoparticles.
Applications of
23
ZnCl , or CuCl ; heterogeneous acid catalysts, like Al-MCM-41 or magnetic nanoparticles (MNPs) in different industrial and bio-
2
2
24
25,26
FeCl3 embedded in Al-MCM-41;
nanocomposites;
logical elds, such as in magnetic resonance imaging, drug
delivery, bioseparation, hyperthermia treatment, and catalytic
36–39
processes, have been demonstrated.
Among the various
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan,
magnetic nanoparticles under investigation, Fe O nanoparticles
3
4
8
+
†
7317, I. R. Iran. E-mail: m.moradian@kashanu.ac.ir; Fax: +98-03155912397; Tel:
98-03155913055
(
Fe O NPs) are arguably the most extensively studied NPs.
3 4
The main characteristics of these nanoparticles are their
Electronic supplementary information (ESI) available: FT-IR and H-NMR
simplicity and their easy separation from reaction media using
spectroscopy data. See DOI: 10.1039/d0ra09929e
©
2021 The Author(s). Published by the Royal Society of Chemistry
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a magnetic eld. Furthermore, the surfaces of magnetic metal deionized water and 50 mL of dry ethanol before being soni-
oxide NPs, such as magnetic Fe O nanoparticles, can be cated for 10 min. Aer that, 40 mL of NH OH was added to the
3
4
4
functionalized and modied with various organic and inorganic reaction mixture and it was sonicated again for 10 min. Then,
40,41
materials.
In this study, a morpholine sulfate acidic ionic 3 mL of tetraethyl orthosilicate (TEOS) dissolved in 25 mL of
liquid was bonded to magnetite nanoparticles (Mag@Morph- ethanol was added dropwise to the solution at room tempera-
AIL) as an efficient catalyst, and it was used for the prepara- ture. Then, the reaction was allowed to proceed under contin-
tion of 3,4-dihydropyrimidinones. Also, we managed to uous magnetic stirring for 18 h. The nal product was separated
synthesize two new derivatives of 3,4-dihydropyrimidinones (4k from solution, washed several times with deionized water and
44
and 4o).
ethanol, and then dried at room temperature for 8 h.
Preparation of Fe O @SiO /TES-Cl. Fe O @SiO (1 g) was
3
4
2
3
4
2
dispersed in 50 mL of toluene and sonicated for 60 min. Then 3-
chloropropyl-triethoxysilan (10 mmol) was added dropwise to
the reaction mixture and it was sonicated for 30 min. The
Experimental
Materials and method
ꢀ
resultant mixture was subsequently reuxed at 140 C under
The chemicals used in this work were purchased from Fluka
and Merck Chemical Companies and were used without puri-
vigorous stirring for 24 h. The obtained bright brown nano-
particles were magnetically separated, consecutively washed
twice with toluene and twice with ethanol, and then dried at

cation. Infrared (IR) spectra were obtained in KBr pellet form
using a PerkinElmer 781 spectrophotometer and an Impact 400
Nicolet FT-IR spectrophotometer. Proton and carbon nuclear
ꢀ
45
6
0 C in an oven.
1
13
Preparation of Fe O @SiO /TES-morpholine. 1 g of Fe -
3
4
2
3
magnetic resonance ( H-NMR and C-NMR) spectra were
recorded in CDCl or DMSO solvent using a Bruker DRX-400
O @SiO –Cl in 50 mL of CH CN was sonicated for 30 min.
4
2
3
3
Then, a solution containing 1.3 mL of morpholine (15 mmol)
and 0.1 mL of triethylamine was added dropwise to the reaction
mixture, which was then reuxed for 24 h. The solid product
was separated from the solution using a bar magnet, washed
spectrometer with tetramethylsilane as an internal reference.
The X-ray diffraction analysis (XRD) patterns of samples were
obtained using a Philips Xpert X-ray powder diffractometer
(CuK radiation, l ¼ 0.154056 nm). Energy-dispersive X-ray
ꢀ
with deionized water/ethanol, and nally dried at 60 C in an
spectroscopy (EDX) spectra of the nanoparticles were obtained
using a Sigma ZEISS, Oxford Instruments eld-emission scan-
ning electron microscope. The melting points of products were
determined using Electrothermal 9200 apparatus and values
were uncorrected. Determination of the purity of substrates and
reaction monitoring was accomplished via thin-layer chroma-
tography (TLC) on silica gel Polygram SILG/UV 254 plates (from
Merck Company). Thermogravimetric and differential thermal
analysis (TGA-DTA) data were obtained using a Bahr STA-503
46
oven.
Preparation of Mag@Morph-AIL. To create a dispersion, 1 g
of the prepared magnetite Fe O @SiO /TES-morpholine nano-
3
4
2
particles was sonicated in 50 mL of dry ethanol for 15 min.
Then, sulfuric acid (0.65 mL, 12 mmol) was added dropwise to
the reaction mixture and it was reuxed for 4 h. The obtained
powder was successfully separated using a bar magnet and
washed with ethanol (3 ꢂ 30 mL) to remove the remaining acid,
before being dried overnight at room temperature.
ꢀ
ꢁ1
instrument in air at a heating rate of 10 C min . Transmission
electron microscopy (TEM) images were recorded using a Zeiss-
EM10C microscope with an acceleration voltage of 100 kV.
General procedure for the synthesis of 3,4-
dihydropyrimidinones
General procedure for the synthesis of the functionalized
magnetic nanocatalyst
Ethyl acetoacetate (1 mmol), aromatic aldehyde (1 mmol), urea
(1.5 mmol) and 0.06 g of Mag@Morph-AIL as catalyst were
Synthesis of Fe
synthesized via
3
O
a
4
nanoparticles. Fe
3
O
4
nanoparticles were added to 30 mL of absolute ethanol in a 50 mL round-bottomed
ꢀ
chemical co-precipitation method. An ask, and the mixture was mechanically stirred at 80 C for an
2
+
3+
3 2
aqueous solution of FeCl and FeCl with an Fe /Fe molar appropriate amount of time. Aer the completion of the reac-
ratio of 1/2 was prepared and kept at room temperature. For this tion as monitored via TLC, 10 mL of ethanol was added to the
purpose, 4.05 g of FeCl $6H O and 1.5 g of FeCl $4H O were reaction mixture and stirring was continued at ambient
3
2
2
2
dissolved in 100 mL of deionized water with the help of an temperature for 10 min. The catalyst was easily isolated using
ultrasonic probe. Then, 30 mL of 25% NH OH was added into a bar magnet, and the product was obtained aer the removal of
4
the solution under nitrogen gas under vigorous stirring. The the solvent under reduced pressure. Then, the product was
ꢀ
reaction was stirred and reuxed for 1 h at 90 C under reux. treated with water followed by crystallization from EtOH. The
1
Aer adding NH
4
OH to the solution, the colour of the solution products were characterized based on H-NMR, FT-IR, and
turned black. The magnetite precipitate was isolated via melting point analysis, and the spectral data of the synthesized
magnetic decantation, which included washing several times compounds were compared with authentic samples. The data is
ꢀ
with deionized water and ethanol, and then drying at 80 C for given below.
4
2,43
10 h in an oven.
Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-
ꢀ
Preparation of Fe O @SiO . The Stober method was used for 5-carboxylate (4a). White solid; mp ¼ 205–209 C; IR (KBr) n
3
4
2
ꢁ1
the preparation of the shell structure (Fe
3 4 2
O @SiO ). 1 g of (cm ): 3245 (NH), 3119 (NH), 2978 (C–H), 1702 (C]O), 1647,
1
magnetite nanoparticles was dispersed in a solution of 10 mL of 1464 (C]C), 1223, 1092 (C–O); H-NMR (CDCl
3
, 400 MHz)
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d (ppm): 1.18 (t, J ¼ 14 Hz, 3H, CH
3
), 2.36 (s, 3H, CH
3
), 4.07 (q,
Ethyl
4-(4-nitrophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
ꢀ
2
H, CH ), 5.40 (s, 1H, CH), 5.64 (s, 1H, NH), 7.28–7.33 (m, 5H), pyrimidine-5-carboxylate (4i). White solid; mp ¼ 197–205 C;
2
ꢁ
1
7.72 (s, 1H, NH).
IR (KBr) n (cm ): 3240 (NH), 3122 (NH), 2985 (C–H), 1703 (C]
1
Ethyl 4-(2-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro- O), 1644, 1463 (C]C), 1521, 1394 (N–O), 1217, 1092 (C–O); H-
ꢀ
pyrimidine-5-carboxylate (4b). White solid; mp ¼ 242–245 C; NMR (DMSO-d6, 400 MHz) d (ppm): 1.09 (t, J ¼ 13.2 Hz, 3H,
ꢁ
1
IR (KBr) n (cm ): 3234 (NH), 3099 (NH), 2934 (C–H), 1704 (C] CH ), 2.25 (s, 3H, CH ), 3.97 (q, 2H, CH O), 5.26 (s, 1H, CH),
3
3
2
1
O), 1643, 1444 (C]Carom), 1221, 1080 (C–O); H-NMR (DMSO- 7.49 (d, J ¼ 7.2 Hz, 2H), 7.89 (s, 1H, NH), 8.21 (d, J ¼ 7.2 Hz, 2H),
d6, 400 MHz) d (ppm): 0.97 (t, J ¼ 14 Hz, 3H, CH
3
), 2.28 (s, 9.36 (s, 1H, NH).
3
3
H, CH
3
), 3.88 (q, 2H, CH
2
O), 5.61 (s, 1H, CH), 7.21–7.37 (m,
Ethyl 4-(anthracen-9-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
ꢀ
H), 7.39 (d, J ¼ 6.8 Hz, 1H), 7.71 (s, 1H, NH), 9.26 (s, 1H, NH). pyrimidine-5-carboxylate (4j). Green solid; mp ¼ 280–285 C;
ꢁ
1
Ethyl 4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro- IR (KBr) n (cm ): 3226 (NH), 3111 (NH), 2972 (C–H), 1693 (C]
ꢀ
1
pyrimidine-5-carboxylate (4c). White solid; mp ¼ 210–212 C; O), 1635, 1451 (C]C), 1230, 1099 (C–O); H-NMR (DMSO-d6,
ꢁ
1
IR (KBr) n (cm ): 3243 (NH), 3118 (NH), 2926 (C–H), 1705 (C] 400 MHz) d (ppm): 0.17 (t, J ¼ 14 Hz, 3H, CH ), 2.22 (s, 3H,
3
1
O), 1647, 1461 (C]C), 1222, 1089 (C–O); H-NMR (DMSO-d6, CH ), 3.34 (q, 2H, CH O), 3.39 (s, 1H, CH), 7.00 (d, J ¼ 10 Hz,
3
2
4
CH
2
00 MHz) d (ppm): 1.07 (t, J ¼ 12.4 Hz, 3H, CH ), 2.23 (s, 3H, 1H), 7.49 (t, J ¼ 20 Hz, 4H), 7.69 (s, 1H, NH), 8.07 (d, J ¼ 8 Hz,
3
3
), 3.95 (q, 2H, CH
2
O), 5.12 (s, 1H, CH), 7.23 (d, J ¼ 7.2 Hz, 2H), 8.41 (s, 1H), 8.55 (d, J ¼ 13.6 Hz, 1H), 9.26 (s, 1H, NH).
Ethyl 4-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-6-methyl-2-
H), 7.38 (d, J ¼ 6 Hz, 2H), 7.77 (s, 1H, NH), 9.25 (s, 1H, NH).
Ethyl 4-(3-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro- oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylate (4k). Yellow
pyrimidine-5-carboxylate (4d). Milky solid; mp ¼ 159–163 C; solid; mp ¼ 269–275 ꢀC; IR (KBr) n (cm ): 3358 (NH), 3120
ꢀ
ꢁ1
ꢁ1
IR (KBr) n (cm ): 3517 (OH), 3243 (NH), 3199 (NH), 2978 (C–H), (NH), 2974 (C–H), 1702 (C]O), 1673 (C]O), 1639, 1447 (C]C),
1
1
1723 (C]O), 1639, 1455 (C]C), 1222, 1092 (C–O); H-NMR 1223, 1087 (C–O); H-NMR (DMSO-d6, 400 MHz) d (ppm): 1.00
(
2
(
DMSO-d6, 400 MHz) d (ppm): 1.10 (t, J ¼ 14 Hz, 3H, CH
3
), (t, J ¼ 8 Hz, 3H, CH ), 2.30 (s, 3H, CH ), 3.90 (q, 2H, CH O), 5.60
3
3
2
.22 (s, 3H, CH
3
), 3.98 (q, 2H, CH
2
O), 5.08 (s, 1H, CH), 6.58–6.70 (s, 1H, CH), 7.64 (s, 1H, NH), 7.67 (d, J ¼ 8 Hz, 1H), 7.87 (s, 1H),
m, 3H), 7.08 (dd, J ¼ 15.2 Hz, 1H), 7.68 (s, 1H, NH), 9.15 (s, 1H, 7.92 (d, J ¼ 8 Hz, 1H), 7.99 (d, J ¼ 8 Hz, 2H), 8.15 (dd, J ¼ 24 Hz,
NH), 9.36 (1H, OH).
Ethyl 4-(2,4-dichlorophenyl)-6-methyl-2-oxo-1,2,3,4-
2H), 9.30 (s, 1H, NH).
Ethyl 4-(4-methylphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
ꢀ
tetrahydro-pyrimidine-5-carboxylate (4e). White solid; mp ¼ pyrimidine-5-carboxylate (4l). Yellow solid; mp ¼ 201–204 C;
ꢀ
ꢁ1
ꢁ1
2
49–250 C; IR (KBr) n (cm ): 3219 (NH), 3106 (NH), 2970 (C– IR (KBr) n (cm ): 3244 (NH), 3115 (NH), 2979 (C–H), 1705 (C]O),
1
H), 1699 (C]O), 1643 (C]C), 1456 (C]C), 1225, 1096 (C–O); 1647, 1460 (C]C), 1222, 1089 (C–O), H-NMR (DMSO-d6, 400
1
H-NMR (CDCl
.27 (s, 3H, CH
3
, 400 MHz) d (ppm): 1.00 (t, J ¼ 12 Hz, 3H, CH
3
), MHz) d (ppm): 1.11 (t, J ¼ 8 Hz, 3H, CH ), 2.22 (s, 3H, CH ), 2.24 (s,
3
3
2
3
), 3.90 (q, 2H, CH
2
O), 5.58 (s, 1H, CH), 7.41 (d, J 3H, CH ), 3.95 (q, 2H, CH O), 5.09 (s, 1H, CH), 7.06 (d, J ¼ 9.6 Hz,
3
2
¼
8 Hz, 1H), 7.31 (d, J ¼ 6 Hz, 1H), 7.55 (s, 1H, NH), 7.75 (s, 1H), 2H), 7.10 (d, J ¼ 9.6 Hz, 2H), 7.66 (s, 1H, NH), 9.15 (s, 1H, NH).
9
.31 (s, 1H, NH).
Ethyl
4-(3,4-dimethoxylphenyl)-6-methyl-2-oxo-1,2,3,4-
Ethyl 4-(2-bromophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro- tetrahydro-pyrimidine-5-carboxylate (4m). Milky solid; mp ¼
ꢀ
ꢀ
ꢁ1
pyrimidine-5-carboxylate (4f). Yellow solid; mp ¼ 180–190 C; 178–178.5 C; IR (KBr) n (cm ): 3248 (NH), 3119 (NH), 2934 (C–
ꢁ
1
1
IR (KBr) n (cm ): 3226 (NH), 3112 (NH), 2976 (C–H), 1695 (C] H), 1706 (C]O), 1652, 1459 (C]C), 1232, 1092 (C–O); H-NMR
1
O), 1639, 1450 (C]C), 1227, 1096 (C–O); H-NMR (DMSO-d6, (CDCl , 400 MHz) d (ppm): 1.20 (t, J ¼ 14 Hz, 3H, CH ), 2.35 (s,
3
3
4
CH
00 MHz) d (ppm): 1.06 (t, J ¼ 12 Hz, 3H, CH
3
3 3 3
), 2.44 (s, 3H, 3H, CH ), 3.84 (s, 3H, CH ), 3.87 (s, 3H, CH ), 4.10 (q, 2H,
3
), 4.01 (q, 2H, CH
H), 7.23–7.28 (m, 2H), 7.27 (s, 1H, NH), 7.55 (d, J ¼ 8 Hz, 1H), ¼ 6.4 Hz, 1H), 6.85 (d, J ¼ 8.4 Hz, 1H), 7.89 (s, 1H, NH).
.82 (s, 1H, NH).
Ethyl 4-(4-dimethylaminophenyl)-6-methyl-2-oxo-1,2,3,4-
Ethyl 4-(2-uorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro- tetrahydro-pyrimidine-5-carboxylate (4n). Yellow solid; mp ¼
2
O), 5.85 (s, 1H, CH), 7.16 (dd, J ¼ 14.8 Hz, CH O), 5.61 (s, 1H, CH), 5.66 (s, 1H), 6.75 (s, 1H, NH), 6.80 (d, J
2
1
8
ꢀ
ꢀ
ꢁ1
pyrimidine-5-carboxylate (4g). Yellow solid; mp ¼ 222–228 C; 257–259 C; IR (KBr) n (cm ): 3242 (NH), 3113 (NH), 2930 (C–
ꢁ
1
1
IR (KBr) n (cm ): 3229 (NH), 3113 (NH), 2975 (C–H), 1692 (C] H), 1702 (C]O), 1646, 1453 (C]C), 1225, 1090 (C–O); H-NMR
1
O), 1642, 1459 (C]C), 1228, 1100 (C–O); H-NMR (DMSO-d6, (DMSO-d6, 400 MHz) d (ppm): 1.09 (t, J ¼ 12 Hz, 3H, CH ), 2.21
3
4
00 MHz) d (ppm): 1.12 (t, J ¼ 12 Hz, 3H, CH
3
3 3 2
), 2.41 (s, 3H, (s, 3H, CH ), 2.83 (s, 6H, CH ), 3.94 (q, 2H, CH O), 5.01 (s, 1H,
CH
H), 7.03 (d, J ¼ 8 Hz, 1H), 7.08 (dd, J ¼ 12 Hz, 1H), 7.14 (s, 1H, NH), 9.26 (s, 1H, NH).
NH), 7.23 (dd, J ¼ 16 Hz, 1H), 8.16 (s, 1H, NH).
Ethyl 4-(isopentyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
Ethyl
4-(3-nitrophenyl)-6-methyl-2-oxo-1,2,3-tetrahydro- pyrimidine-5-carboxylate (4o). Orange color solid; mp ¼ 168–
3
), 4.04 (q, 2H, CH
2
O), 5.65 (s, 1H, CH), 5.7 (d, J ¼ 14.4 Hz, CH), 6.64 (d, J ¼ 8.4 Hz, 2H), 7.03 (d, J ¼ 8.4 Hz, 2H), 7.57 (s, 1H,
1
ꢀ
ꢀ
ꢁ1
pyrimidine-5-carboxylate (4h). White solid; mp ¼ 125–128 C; 170 C; IR (KBr) n (cm ): 3240 (NH), 3112 (NH), 2954 (C–H),
ꢁ
1
1
IR (KBr) n (cm ): 3217 (NH), 3101 (NH), 2964 (C–H), 1707 (C] 1706 (C]O), 1651, 1466 (C]C), 1219, 1085 (C–O); H-NMR
1
O), 1628, 1455 (C]C), 1526, 1374 (N–O), 1223, 1088 (C–O); H- (DMSO-d6, 400 MHz) d (ppm): 0.84 (d, J ¼ 6 Hz, 6H, CH ),
3
NMR (DMSO-d6, 400 MHz) d (ppm): 1.08 (t, J ¼ 13.6 Hz, 3H, 1.10 (q, 2H, CH ), 1.18 (t, J ¼ 14 Hz, 3H, CH ), 1.35 (q, 2H, CH ),
2
3
2
3 3 2
3 2
CH ), 2.25 (s, 3H, CH ), 3.99 (q, 2H, CH O), 5.28 (s, 1H, CH), 1.69 (m, 1H, CH), 2.14 (s, 3H, CH ), 3.32 (q, 2H, CH O), 4.04 (t, J
7
.63 (d, J ¼ 7.6 Hz, 1H), 7.68 (dd, J ¼ 20 Hz, 1H), 7.91 (s, 1H, NH), ¼ 12.8 Hz, 1H, CH), 7.43 (s, 1H, NH), 8.95 (s, 1H, NH).
8.07 (s, 1H), 8.13 (d, J ¼ 7.6 Hz, 1H), 9.38 (s, 1H, NH).
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Results and discussion
Structural analysis of the Mag@Morph-AIL nanocatalyst
In this work, green and effective methods were used to produce
+
ꢁ
Fe
particles were prepared via a chemical co-precipitation method.
Then, a SiO shell was coated on the magnetite core via the
3
O
4
@SiO
2
/TES-Mo HSO
4
nanoparticles. Fe
3
O
4
nano-
2
Stober method. Finally, CPTES (chloropropyltriethoxysilane)
and morpholine were coated on the SiO2 shell. The
Mag@Morph-AIL nanoparticles were an efficient catalyst that
were used for the preparation of 3,4-dihydropyrimidinones
(Scheme 1).
FT-IR spectra of Fe
are shown in Fig. 1. In the FT-IR spectrum of Fe O
3 4
at 3410 and 1625 cm
bending vibrations, respectively, and the peak at 583 cm
3
O
4
, Fe
3
O
4
@SiO
2
, and Mag@Morph-AIL
, the peaks
correspond to O–H stretching and
ꢁ
1
ꢁ1
Fig. 1 FT-IR spectra of (a) Fe O , (b) Fe O @SiO , and (c) Mag@-
3
4
3
4
2
corresponds to Fe–O stretching vibrations. In the FT-IR spec- Morph-AIL.
ꢁ1
trum of Fe O @SiO (Fig. 1b), the peak at 1092 cm corre-
3
4
2
sponds to Si–O stretching vibrations.
In the FT-IR spectrum of Mag@Morph-AIL (Fig. 1c), the S]O nature. The catalyst shows high magnetic permeability and high
stretching vibrations of the –HSO group appeared at 1100– hysteresis loop reversibility. The decrease in the level of catalyst
250 cm with a high relative intensity. The peaks at 1467 and magnetism relative to the initial state indicates the presence of
4
ꢁ
1
1
1
ꢁ
1
634 cm correspond to N–H and O–H bending vibrations, organic groups on the primary surface.
ꢁ
1
respectively, and the peak at 3425 cm corresponds to N–H and
O–H stretching vibrations.
As indicated in Fig. 3, the levels of saturation magnetiza-
ꢁ1
tion for Fe O @SiO and Mag@Morph-AIL are 50.86 emu g
3
4
2
ꢁ
1
As shown in Fig. 2, the XRD patterns of Fe O , Fe O @SiO , and and 13.84 emu g , respectively. These results determine that
3
4
3
4
2
Mag@Morph-AIL nanoparticles are provided. The patterns agree the magnetization properties decrease upon coating and
well with the reported pattern for Fe nanoparticles. The XRD functionalization. According to these results, the catalyst can
pattern of Mag@Morph-AIL includes peaks from Fe and the be easily separated and recovered using an external magnetic
3 4
O
3 4
O
silica layer. According to the Scherrer equation utilizing the eld.
FWHM, the average crystalline size of the Mag@Morph-AIL
As shown in Fig. 4, scanning electron microscopy (SEM)
nanoparticles that were obtained was calculated to be 10–15 nm. imaging indicates that the prepared Mag@Morph-AIL NPs
As shown in Fig. 3, the hysteresis loops of the samples are possess an average diameter of about 65 nm, and the nano-
completely reversible, conrming their superparamagnetic particles show good dispersity with spherical morphology. A
TEM image of the Mag@Morph-AIL nanoparticles is shown
in Fig. 4d. Here, the TEM image gives more accurate infor-
mation about the particle size and morphology of the nano-
material. The TEM image reveals the spherical shape of the
3 4 3 4 2
Fig. 2 The XRD patterns of (a) Fe O , (b) Fe O @SiO , and (c)
Scheme 1 The preparation of the catalyst Mag@Morph-AIL.
Mag@Morph-AIL.
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Fig. 5 The EDX spectrum of Mag@Morph-AIL.
3 4 2
Fig. 3 Magnetization versus the applied field for (a) Fe O @SiO and
(
b) Mag@Morph-AIL.
thermal analysis revealed that the thermal decomposition of
the organic moieties was completed at a temperature of
ꢀ
7
90 C.
magnetic nanomaterial, with an average size of 69 nm, which
shows close agreement with the value determined via SEM,
while being larger than the value obtained via XRD analysis.
Also, as seen in Fig. 5, the EDX spectrum of the synthesized
Mag@Morph-AIL NP catalyst was obtained, in which the ex-
pected elemental composition (C, N, O, Si, S, and Fe) is
shown clearly.
Thermogravimetric analysis can be used to estimate the
amount of catalytically active species on the solid nano-
composite material. To calculate the amount of organic moie-
ties (mmol g ), the solid catalyst weight-loss value of 26% w/w
that can be attributed to organic functional groups was used in
conjunction with the molecular weight of the organic moieties.
According to these data, the amount of organic active species
ꢁ
1
As shown in Fig. 6, the thermal behavior of the Mag@Morph-
AIL nanocatalyst was studied. The TG prole exhibited two
weight loss steps. An initial mass loss of 4% with an endo-
thermic peak in the DTA curve is revealed in the temperature
ꢁ1
anchored on the surface of the solid catalyst is 1.070 mmol g
.
The amount of acid in the catalyst was quantitatively
4
7
estimated via ion-exchange pH analysis. For this purpose,
75 mg of solid catalyst was added to an aqueous solution of
NaCl (1 M, 50 mL), and the resulting mixture was stirred for 3
days. The nal mixture was titrated using 0.05 M NaOH
solution. The amount of acid in the Mag@Morph-AIL catalyst
was determined to be 1.862 mmol g , which appears to be
a good approximation because it is twice the amount of
organic species estimated via TGA and each organic moiety
has two acidic hydrogens.
ꢀ
range of 100–150 C. This can be related to the release of
physically absorbed water on the surface of the nanomaterial.
The second mass loss of 30% occurred in a wide temperature
ꢀ
range of 420–500 C, which overlapped with a broad endo-
ꢁ
1
thermic DTA peak. This corresponds mainly to the thermal
decomposition of the organic complex. The results of
Catalytic performance of the solid acidic ionic liquid for the
Biginelli reaction
Mag@Morph-AIL, as an organic–inorganic hybrid nano-
material, when used as a catalyst in the Biginelli reaction,
3 4 3 4 2
Fig. 4 SEM images of (a) Fe O , (b) Fe O @SiO , and (c) Mag@Morph-
AIL, and (d) a TEM image of Mag@Morph-AIL.
Fig. 6 TGA and DTA curves of Mag@Morph-AIL.
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Table
2
The effects of temperature on the synthesis of 3,4-
a
dihydropyrimidinones
ꢀ
b
Entry
Temperature ( C)
Time (min)
Yield (%)
1
2
3
4
60
70
80
90
120
90
60
60
75
92
92
Scheme 2 The use of Mag@Morph-AIL in the Biginelli reaction.
showed signicant advantages, such as biocompatibility,
60
a
Reaction conditions: p-methyl benzaldehyde (1 mmol), ethyl
acetoacetate (1 mmol), urea compound (1.5 mmol) and Mag@Morph-
magnetic separability and recoverability, thermal stability, AIL catalyst (0.06 g) were reuxed in EtOH (5 mL). Isolated yield.
b
a high surface area, and a higher loading of active sites.
Moreover, the introduction of sulfonic acid and organic
groups onto the surface of Fe O @SiO is interesting since
3
4
2
dihydropyrimidinones with a catalytic amount of Mag@Morph-
AIL NPs in a simple reaction. With reference to the results in
Table 3, polar and protic solvents increased the rate of reaction,
and EtOH provided excellent yields and proved to be the solvent
of choice.
the combination of both acidic and hydrophobic function-
alities allows for the creation of a less-polar organic envi-
ronment with relatively strong acidity, leading to a “quasi-
homogeneous” catalyst for acid-catalyzed reactions.
However, in many acid-catalyzed reactions using silica-based
solid acids, the water produced as a by-product can be
adsorbed on the surface of silanol, thus poisoning the
surface, reducing the performance of the catalyst, and deac-
tivating the active acidic sites of the catalyst.
To begin this study, the reaction conditions, such as the
solvent, temperature, and the amount of catalyst, were opti-
mized (Scheme 2). For this purpose, the reaction between
benzaldehyde (1.0 mmol), ethyl acetoacetate (1.0 mmol), and
urea (1.5 mmol) as substrates with the prepared nano-
composite material as a catalyst under reux conditions was
selected as the model reaction. At rst, the optimum amount
of catalyst was investigated in ethanol solvent (Table 1). It
was found that the best results were obtained when the
reaction was carried out in the presence of 0.06 g of catalyst
In continuation of this research, as shown in Table 4, the
corresponding products were obtained in excellent yields and
with short reaction times under the optimum conditions. To
ascertain the scope and limitations of this reaction, some
aliphatic and aromatic aldehydes were reuxed with urea and
ethyl acetoacetate in the presence of 0.06 g of Mag@Morph-
ꢀ
AIL NPs with ethanol as the solvent at 80 C. A best isolated
yield of product of 93% was obtained within 58 min (Table 4).
The desired 3,4-dihydropyrimidinone derivatives were
synthesized and then characterized via spectroscopic
methods.
Reusability of the Mag@Morph-AIL nanocatalyst
The Mag@Morph-AIL nanocatalyst is recoverable without
a considerable loss of catalytic activity. Aer the completion of
the reaction, 5 mL of ethanol was added to the reaction mixture
and the nanocatalyst was recycled using an external magnetic
(
Table 1, entry 4).
In order to optimize the temperature of the reaction, the
reaction was performed at different temperatures in the pres-
ence of 0.06 g of catalyst and with ethanol as the solvent. With
reference to the results shown in Table 2, it was found that the

eld and washed with acetone to remove residual product or
other organic material. The nanocatalyst was reused for a new
Biginelli reaction between p-methyl benzaldehyde, ethyl ace-
toacetate, and urea under similar reaction conditions. As shown
in Fig. 7, the NPs could be reused for up to eight cycles with an
insignicant loss of catalytic activity, providing the product in
high yields.
best results were obtained when the reaction was carried out at
ꢀ
8
0 C (Table 2, entry 3).
In an effort to obtain better yields and the most effective
solvent, various solvents were used for the synthesis of 3,4-
Table 1 Optimization of the catalyst amount for the formation of 3,4-
dihydropyrimidinones
a
Table
3 The effects of the solvent on the synthesis of 3,4-
a
dihydropyrimidinones
b
Entry
Catalyst amount (g)
Time (min)
Yield (%)
b
Entry
Catalyst amount (g)
Time (min)
Yield (%)
1
2
3
4
5
0.01
0.02
0.04
0.06
0.08
150
100
80
60
60
70
75
92
92
92
1
2
3
4
THF
CH CN
EtOH
150
130
60
50
44
92
35
3
DMSO
120
a
a
Reaction conditions: p-methyl benzaldehyde (1 mmol), ethyl
Reaction conditions: p-methyl benzaldehyde (1 mmol), ethyl
acetoacetate (1 mmol), urea compound (1.5 mmol), and Mag@Morph- acetoacetate (1 mmol), urea compound (1.5 mmol), and Mag@Morph-
ꢀ
AIL catalyst (0.06 g) were reuxed in the selected solvent (5 mL) at
AIL catalyst were added to EtOH as the solvent (5 mL) at 80 C.
b
ꢀ
b
Isolated yield.
80 C. Isolated yields.
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a
Table 4 The synthesis of 3,4-dihydropyrimidinones using Mag@Morph-AIL
b
c
d
ꢀ
Entry
1
Name
Product
Time (min)
Yield (%)
MP ( C)
4a
64
65
86
88
204–206 (ref. 47)
2
4b
252–253 (ref. 48)
3
4
5
4c
4d
4e
60
70
60
87
85
89
206–208 (ref. 49)
167–170 (ref. 49)
251–254 (ref. 49)
6
7
4f
65
70
86
88
185–188 (ref. 44)
224–225 (ref. 52)
4g
8
9
4h
4i
60
58
90
93
123–126 (ref. 47)
205–208 (ref. 51)
1
0
4j
70
89
283–285 (ref. 53)
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Table 4 (Contd.)
b
c
d
ꢀ
Entry
Name
Product
Time (min)
66
Yield (%)
MP ( C)
1
1
2
4k
91
92
272–275 (ref. 52)
1
4l
60
75
75
206–207 (ref. 49)
176–179 (ref. 49)
258–261 (ref. 50)
1
1
3
4
4m
4n
85
87
1
5
4o
80
80
169–173 (ref. 44)
a
Reaction conditions: benzaldehyde (1 mmol), ethyl acetoacetate (1 mmol), urea compound (1.5 mmol) and Mag@Morph-AIL catalyst (0.06 g) were
b
c
reuxed in EtOH as the solvent (5 mL). All products were characterized based on their spectroscopic data (FT-IR and 1H-NMR). Isolated yield.
d
Literature reference.
catalyst. The novel magnetic recoverable nanocatalyst was
characterized using FT-IR, SEM, EDX, XRD, VSM, and BET
techniques. The catalyst showed excellent efficiency and could
convert >92% of the substrates to the target molecules within
ꢀ
6
0 min at 78 C. The catalyst was recovered using an external
magnet from the reaction mixture and could be recycled for at
least 8 runs without a major decrease in catalytic activity. The
method offers several advantages, including clean reaction
proles, good availability, high yields, short reaction times,
simple experimental procedures, catalyst reusability, and low
catalyst loading.
Conflicts of interest
Fig. 7 Recyclability study of Mag@Morph-AIL.
There are no conicts to declare.
Conclusions
Acknowledgements
In this report, we have developed a straightforward and efficient
method for the synthesis of 3,4-dihydropyrimidinones using
a Mag@Morph-AIL nanocomposite material as a new metal-free
The authors are grateful to the University of Kashan for sup-
porting this work (grant no. 159148).
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