Fe3O4@SiO2·HM·SO3H as a recyclable heterogeneous nanocatalyst for the microwave-promoted synthesis of 2,4,5-trisubstituted imidazoles under solvent free conditions

Article abstract of DOI:10.1039/c5nj01273b

A simple, highly versatile and efficient synthesis of 2,4,5-trisubstituted imidazoles is achieved through a three component one pot reaction of benzil, benzaldehyde and NH₄OAc. This reaction has been catalyzed by Fe₃O₄@SiO₂·HM·SO₃H, a very efficient, novel recyclable heterogeneous catalyst, under microwave irradiation and solvent free conditions. The catalyst can be recovered for the subsequent reactions and reused for at least five rounds, without any appreciable loss of its efficiency.

Full text of DOI:10.1039/c5nj01273b

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DOI: 10.1039/C5NJ01273B
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Article
Fe3O4@SiO2.HM.SO3H as a recyclable heterogeneous
nanocatalyst for microwave-promoted synthesis of
2,4,5-trisubstituted imidazoles under solvent free
condition
HosseinNaeimi*, Dorsa Aghaseyedkarimi
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan,
87317, I.R. Iran
Abstract: A simply,highly versatile and efficient synthesis of 2,4,5ꢀtrisubstituted imidazoles is
achievedthrough three component one pot reaction of benzil, benzaldehyde and NH4OAc. This
reaction has been catalyzed by Fe3O4@SiO2.HM.SO3H as a very efficient, novel recyclable
heterogeneous catalyst, under microwave irradiation and solvent free condition. The catalyst
can be recovered for the subsequent reactions and reused for at least five rounds, without any
appreciable loss of its efficiency.
separated by magnetic separation9. Magnetite nanoparticles are not
very stable under ambient conditions, and are easily oxidized to
magnetite or dissolved in an acidic medium10.
1. Introduction
Imidazole derivativesare very important because of their
A silica shell does not only protect the magnetic core, but can
also prevent the direct contact of the magnetic core with additional
agents linked to the silica surface thus avoiding unwanted
interactions. The surfaces of silica coated magnetic nanoparticles can
readily modify with functional groups11. In this article, silica coated
magnetite nanoparticles have been functionalized with multiꢀSO3H
functionalized acidic ionic liquid, so it shows strong catalytic
activity for one pot green synthesis of 2,4,5ꢀtrisubstituted imidazoles
under microwave irradiation.
diverse biological activities in pharmaceuticals as well as
agrochemical field1. Moreover the imidazole nucleus constitutes the
2, 3
core unit of many natural products
such as; essential aminoacids
histidine, histamine and pilocarpine alkaloids. Also, 2,4,5ꢀtriaryl
imidazoles are popular building blocks for the construction of
pharmaceutically interesting compounds like; inhibitors of P38 MAP
kinase4, BꢀRaf kinase transforming growth factor b1, fungicides and
herbicides.
Microwave assisted organic synthesis (MAOS) has had a
significant impact on synthetic chemistry since the introduction of
controlled, precise microwave reactors. In comparison with
conventional thermal heating using microwave irradiation in
chemical reactions, has some advantages such as reductions in
reaction times, increase in yield and suppression of side product
formation, a vast improvement in operations like distillation, and
considerable saving in energy5.
In comparison between microwave and conventional heating,
in case of using microwave the heating is created in the interior of
the sample and is then radiated outward, but in conventional heating
the heat is generated in the outer region and must then be directed
towards the center.
Heterogeneous catalysis has been known for many years and
has become strategically vital for the efficient and ecoꢀfriendly
organic transformations over the past few decades6ꢀ8. Magnetite is an
ideal oxide support, easy to prepare, having a very active surface for
adsorptions or immobilization of metals and ligands, which can be
2. Experimental
2.1. Chemicals
All commercially available reagents were used without further
purification and purchased from Merck, Chemical Company in
high purity. The used solvents were purified by standard
procedure.
2.2. Apparatus
Products were characterized by comparison of their physical
data; IR and 1H NMR and 13C NMR spectra with known
samples. Fourier transform infrared (FTꢀIR) spectra were
obtained using a PerkinꢀElmer 781 spectrophotometer. The
NMR spectra were recorded on a Bruker Advance DPX 400
MHz instrument spectrometer at 400 and 100 MHz in DMSO
and Acetone as solvent in the presence of tetramethylsilane
(TMS) as internal standard. Thereaction monitory was
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New Journal of Chemistry
DOI: 10.1039/C5NJ01273B
accomplished by TLC on silica gel Poly Gram SILG/UV 254 room temperature, the intermediate was collected by
nm plates. Field emission scanning electron microscopy (FE permanent magnet and rinsed thrice with ethanol (30 ml).
a
SEM) images were obtained by HITACHI Sꢀ4160. Xꢀray The concentrated H2SO4 (0.154 ml, 3mmol) was added to the
diffraction patterns of samples were taken on a Philips Xpert Xꢀ mixture of above intermediate and ethanol as solvent under
ray powder diffraction diffractometer (Cuk, radiation, k= reflux for 2h to form the ionic liquid. The final catalyst was
0.154056 nm). Melting points were measured on a Yanagimoto then washed repeatedly with ethanol to remove nonionic
micro melting point apparatus. To produce ultrasonic residues and then dried.
irradiation, the Bandelin ultrasonic HD 3200 with probe model
KE 76.6 mm diameter. The amount of ionic liquid coated
MNPs was estimated using energy dispersive Xꢀray
spectroscopy (SEMꢀEDX).
2.4. General procedure for synthesis of substituted
imidazoles in the presence of Fe3O4@SiO2.HM.SO3H.
The reported synthesis of 2,4,5ꢀtrisubstituted imidazoles
involve the reaction of 0.21 g benzil (1mmol), 0.35 g
ammonium acetate (2mmol) and a substituted benzaldehyde
2.3. Catalyst preparation
New Fe3O4@SiO2.HM.SO3H was prepared based on the (1mmol). These reagents were mixed together and treated in the
following procedure.
presence of catalyst (0.060 g) under microwave irradiation and
solvent free condition. Progress of the reaction was monitored
by TLC (petroleum ether ethyl acetate 7: 3) after the reaction
completed the mixture was cooled and the substrates separated
from the catalyst by dissolving them in acetone. Then the
catalyst was separated by using an external magnet. The
product recrystalization with ethanol or acetone/water obtained
pure 2,4,5ꢀtrisubstituted imidazoles.
General procedure for preparation of nano-Fe3O4
Fe3O4 MNPs were synthesized according to a previously
reported procedure by chemical coꢀprecipitation method
12
.
FeCl3.6H2O (2.7 g) and FeCl2.4H2O (1g) were dissolved in 100
ml of 1.2 mmol.Lꢀ1 aqueous HCl by ultrasonic bath for 30 min.
Then, 1.25 mol.Lꢀ1 aqueous NaOH (150 ml) was added under
vigorous stirring and heated at 80°C under nitrogen atmosphere
and a black precipitate was immediately formed. After 2h, the
precipitate was magnetically separated and washed several
times with water until the supernatant liquor reached neutrality
(pH~7).
2,4,5-triphenyl-1H-imidazole (3a), white solid; m.p.: 274ꢀ
277°C, Lit.16 m.p.: 273ꢀ276°C; IR(KBr)/ν (cmꢀ1): 3426 (NH),
3041(C=CꢀH), 1490(C=N), 1460, 1598 (C=C aromatic);1H
NMR (Acetoneꢀd6, 400 MHz) δ (ppm): 7.36ꢀ8.15 (m, 15H, Arꢀ
H), 11.73(s, 1H, NH); 13C NMR(DMSOꢀd6, 100MHz) δ (ppm):
122.72, 124.07, 125.67, 127.76, 128.72, 128.87, 129.15,
130.81, 136.93, 145.98.
General procedure for preparation of nano-Fe3O4@SiO2
core-shell
The coreꢀshell Fe3O4@SiO2nanospheres were prepared by a
modified Stober method 13, briefly, Fe3O4 (0.5g, 2.1mmol) was
dispersed in the mixture of ethanol (50 ml), deionized water
(5ml) and tetraethoxysilane (TEOS) (0.2ml), followed by the
addition of 5.0 ml NaOH (10 %wt). This solution was stirred
mechanically for 30 min at room temperature. Then the
product, Fe3O4@SiO2, was separated by an external magnet,
and was washed with the mixture of deionized water and
ethanol three times and dried at 80oC for 10 h. FTꢀIR (KBr
pellets, cmꢀ1): 3400 (OꢀH), 1000ꢀ1150 (SiꢀOꢀSi) and 556 (FeꢀO)
2-(3-methoxyphenyl)-4,5-diphenyl-1H-imidazole (3b), white
solid;m.p.: 260ꢀ262 °C, Lit.17m.p.: 259ꢀ262 °C;IR (KBr)/ν (cmꢀ
1): 3425 (NH), 3059(C=CꢀH), 2925 (CꢀCꢀH), 1482 (C=N),
1
1444, 1593 (C=C aromatic), 1239 (CꢀO); H NMR (DNSOꢀd6,
400 MHz) δ (ppm): 3.82 (s, 3H, OMe), 6.94 (s, 1H, ArꢀH),
7.30ꢀ7.67 (m, 13H, ArꢀH), 12.67 (s, 1H, NH); 13C NMR
(DMSOꢀd6, 100MHz) δ (ppm): 55.67, 110.68, 114.70, 118.11,
126.59, 126.94, 127.69, 128.16, 128.89, 129.21, 129.47,
129.67, 130.29, 132.10, 145.85, 160.04.
14
.
2-(3,4-dimethoxyphenyl)-4,5-diphenyl-1H-imidazole
(3c),
white solid; m.p.: 213ꢀ216 °C, Lit.18m.p.: 215ꢀ219 °C;IR
(KBr)/ν (cmꢀ1): 3427 (NꢀH), 3048(C=CꢀH), 2927 (CꢀCꢀH),
1602 (C=C), 1500 (C=N), 1258(CꢀO), 766 (C=CꢀH), 696(C=Cꢀ
H).1H NMR (DNSOꢀd6, 400 MHz) δ (ppm): 12.51 (s, 1H, Nꢀ
H), 7.65 (s, 1H, ArꢀH), 7.4ꢀ 7.55 (m, 6H, ArꢀH), 7.36 (t, 2H, 3J=
7.0 Hz, ArꢀH), 7.28 (t, 2H,3J= 7.6 Hz, ArꢀH), 7.2 (t, 1H, 3J= 7.0
General procedure for preparation of ionic liquid
intermediate
To create an active site for binding to Fe3O4@SiO2, on the ionic
liquid, initially Hexamethylenetetramine (HM) (0.14g, 1mmol)
was mixed with 3ꢀchloropropyltrimethoxysilane (0.18ml,
1mmol) and the mixture was stirred for 6h and heated to 60oC,
under nitrogen atmosphere.
3
Hz, ArꢀH), 7.15 (d, 1H, J= 7.6 Hz, ArꢀH), 3.78 (s, 3H, OCH3),
3.75 (s, 3H, OCH3).13C NMR (DMSOꢀd6, 100MHz) δ (ppm):
148.6, 147.0, 146.3, 137.2, 135.9 131.7, 129.0, 128.8, 128.6,
128.0, 127.5, 126.8, 123.9, 117.0, 113.3, 112.5, 56.1, 55.8 .
Then, this product and 1,4ꢀbutane sultone (0.36 ml, 3 mmol)
were mixed together without solvent and stirred 72h at room
temperature (25oC), and then white solid zwitterions was
formed and the solid was washed repeatedly with ethyl ether.
o
2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole
(3d);
Then it was dried in vacuum (110 C, 0.01 torr). The white
bisque solid ; m.p.: 231ꢀ232 °C, Lit.19m.p.: 230ꢀ232 °C;
IR(KBr) / ν (cmꢀ1): 3423 (NH), 3054 (C=CꢀH), 2837 (CꢀCꢀH),
1459 (C=N), 1447, 1611 (C=C aromatic), 1252 (CꢀO); 1H NMR
(DMSO ꢀd6, 400 MHz) δ (ppm): 3.27 (s,3H,OMe), 7.03ꢀ7.05(d,
2H, J=8 Hz, HꢀAr), 7.28ꢀ7.51 (m, 10H, ArꢀH), 8.00ꢀ8.02(d,
2H, J=8 Hz, HꢀAr),12.64 (s, 1H, NꢀH); 13C NMR(DMSOꢀd6,
100MHz) δ (ppm): 54.78, 114.00, 123.26, 126.83, 127.00,
127.87, 128.28, 133.50, 145.96.
solid zwitterions was obtained in a good yield (>90%) and
sufficient purity 15
.
A
procedure for joining IL to Fe3O4@SiO2 and
functionalization of IL
1.0 g of SiO2ꢀcoated Fe3O4 nanoparticle was dispersed in 50 ml
ethanol by sonication for 1h. An ethanol solution of above
zwitterions was then added, and the reaction mixture was
refluxed for 2 days under nitrogen atmosphere. After cooling to
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2-(2,3-dimethxyphenyl)-4,5-diphenyl-1H-imidazole
(3e)
;
IR(KBr) / ν (cmꢀ1): 3433 (NꢀH), 3062 (C=CꢀH), 2924 (CꢀCꢀH),
white solid; m.p.: 235ꢀ236°C; IR (KBr) / ν (cmꢀ1): 3421 (NH), 1477 (C=N), 1448, 1604 (C=C aromatic), 1054 (CꢀCl); 1H
3056 (C=CꢀH), 2966 (CꢀCꢀH), 1483 (C=N), 1442, 1586 (C=C NMR (DMSOꢀd6, 400 MHz) δ (ppm): 7.24ꢀ7.78 (m, 14H,Arꢀ
aromatic), 1272 (CꢀO); 1H NMR (Acetoneꢀd6, 400 MHz) δ H), 12.64 (s, 1H, NH); 13C NMR(Acetoneꢀd6, 100MHz) δ
(ppm): 2.94(s,3H,OMe), 3.07(s,3H,OMe)7.06ꢀ7.92(m, 13H, Hꢀ (ppm): 127.15, 127.91, 128.35, 129.88, 130.27, 131.21, 131.34,
Ar), 11.20 (s, 1H, NꢀH);13C NMR(DMSOꢀd6, 100 MHz) δ 143.40.
(ppm): 55.02, 58.49, 118.34, 119.04, 123.14, 123.60, 127.86,
128.04, 128.87, 129.03, 129.60, 136.01, 145.92, 147.23, 2-(2,3-dichlorophenyl)-4,5-diphenyl-1H-imidazole (3l); white
150.11; Anal. Calcd. For C23H20N2O2: C 77.51, H 5.66, N 7.86, solid; m.p.: 194ꢀ197 °C; IR(KBr) / ν (cmꢀ1): 3436 (NꢀH), 3059
Found C 78.24, H 5.98, N 7.84.
(C=CꢀH), 2818 (CꢀCꢀH), 1502 (C=N), 1444, 1604 (C=C
aromatic), 1049 (CꢀCl); 1H NMR (DMSOꢀd6, 400 MHz) δ
;
white (ppm): 7.22ꢀ7.74 (m, 13H,ArꢀH), 12.75 (s, 1H, NH); 13C
2-(4-methylphenyl)-4,5-diphenyl-1H-imidazole (3f)
solid;m.p.: 232ꢀ236 °C, Lit.20m.p.: 232ꢀ235 °C; IR(KBr) / ν NMR(DMSOꢀd6, 100MHz) δ (ppm): 126.67, 127.42, 127.98,
(cmꢀ1): 3430 (NꢀH), 3033 (C=CꢀH), 2923 (CꢀCꢀH), 1482 128.08, 128.44, 128.71, 129.70, 130.02, 130.47, 131.17,
1
(C=N), 1448, 1598 (C=C aromatic); H NMR (DMSOꢀd6, 400 132.41, 133.28, 142.93; Anal. Calcd. For C21H14Cl2N2: C
MHz) δ (ppm): 2.34 (s,3H, Me), 7.20ꢀ7.22(d, 2H, J=8 Hz, Hꢀ 69.06, H 3.86, N 7.67, Found C 70.14, H 3.72, N 7.50.
Ar), 7.26ꢀ7.54 (m, 10H, ArꢀH), 7.95ꢀ7.97 (d, 2H, J=8 Hz, Hꢀ
Ar),12.98 (s, 1H, NꢀH); 13C NMR(DMSOꢀd6, 100MHz) δ 2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole (3m); white
(ppm): 21.36, 125.63, 126.94, 127.53, 128.13, 128.16, 128.40, solid; m.p.: 260ꢀ261 °C, Lit.1 m.p.: 262ꢀ264°C; IR(KBr) / ν
128.64, 128.86, 129.11, 129.72, 131.59, 135.69, 137.38, (cmꢀ1): 3420 (NꢀH), 3062 (C=CꢀH), 1485 (C=N), 1443, 1604
1
138.17, 146.13.
(C=C aromatic), 1092 (CꢀCl); H NMR (DMSOꢀd6, 400 MHz)
δ (ppm): 7.20ꢀ8.53 (m, 12H, ArꢀH), 8.61ꢀ8.65 (m, 2H, ArꢀH),
2-(2-hidroxyphenyl)-4,5-diphenyl-1H-imidazole (3g); white 12.76 (s, 1H, NꢀH); 13C NMR(DMSOꢀd6, 100MHz) δ (ppm):
solid; m.p.: 118ꢀ120 °C, Lit.21m.p.: 117ꢀ119 °C; IR(KBr) / ν 126.59, 126.75, 127.36, 127.84, 128.05, 128.38, 128.67,
(cmꢀ1): 3430 (NꢀH), 3033 (C=CꢀH), 2923 (CꢀCꢀH), 1482 135.77, 129.95, 133.46, 144.76.
1
(C=N), 1448, 1598 (C=C aromatic); H NMR (DMSOꢀd6, 400
MHz) δ (ppm): 12.89 (s,1H, OH), 7.00ꢀ7.96(m, 14H, HꢀAr),
2-(2,4-dichlorophenyl)-4,5-diphenyl-1H-imidazole
11.98 (S, NH); 13C NMR(DMSOꢀd6, 100MHz) δ (ppm): (3n);bisque solid; m.p.: 175ꢀ178 °C, Lit.19m.p.: 176.5ꢀ177 °C;
113.82, 117.95, 119.57, 125.27, 127.93, 128.01, 129.09, IR(KBr) / ν (cmꢀ1): 3437 (NꢀH), 3063 (C=CꢀH), 2968 (CꢀCꢀH),
129.21, 129.52, 129.61, 130.99.
1
1475 (C=N), 1448, 1597 (C=C aromatic); H NMR (Acetoneꢀ
d6, 400 MHz) δ (ppm): 7.23ꢀ8.09 (m, 13H, ArꢀH), 11.66 (s, 1H,
4-(4,5-diphenyl-1H-imidazole-2-yl)phenol (3h); light bisque NꢀH).
solid; m.p.: 264ꢀ267 °C, Lit.18m.p.: 268ꢀ270 °C; IR(KBr) / ν
(cmꢀ1): 3408 (NꢀH), 3200 (OH), 3058 (C=CꢀH), 1493 (C=N),
1
3. Results and discussion
1454, 1609 (C=C aromatic), 1254 (CꢀO); H NMR (DMSOꢀd6,
400 MHz) δ (ppm): 6.83ꢀ6.85 (d, 2H, J=8.4 Hz, HꢀAr), 7.28ꢀ
7.51 (m, 10H, ArꢀH), 7.88ꢀ7.90 (d, 2H, J=8.4 Hz, HꢀAr), 9.69
3.1. Preparation of catalyst
(s, 1H, OH), 12.40(s, 1H, NH); 13C NMR(DMSOꢀd6, 100MHz) For the synthesis of catalyst, at first Fe3O4 and tetraethoxysilane
δ (ppm): 115.89, 122.05, 127.35, 128.15, 128.85, 146.55, were mixed together to produce Fe3O4@SiO2. On the other
158.26.
hand, hexamethylentetramine (HM) was reacted with
chloropropyltrimethoxysilane and the product was mixed to
; white 1,4ꢀbutane sultone to produce an ionic liquid intermediate with
2-(3-methylphenyl)-4,5-diphenyl-1H-imidazole (3i)
solid; m.p.: 296ꢀ299 °C, Lit.22 m.p.: 298ꢀ299 °C; IR(KBr) / ν an active site for binding to the MNP@SiO2. The Fe3O4@SiO2
(cmꢀ1): 3423 (NꢀH), 3059 (C=CꢀH), 2924 (CꢀCꢀH), 1483 and activated ionic liquid joined together, the final catalyst was
(C=N), 1448, 1601 (C=C aromatic).1H NMR (DMSOꢀd6, 400 obtained
MHz) δ (ppm): 2.37 (s, 3H, Me), 7.17 (s, 1H, ArꢀH), 7.19ꢀ7.93
(m, 13H, ArꢀH), 12.64 (s, 1H, NH). 13C NMR(DMSOꢀd6,
100MHz) δ (ppm): 21.57, 122.86, 126.23, 126.99, 127.58,
128.20, 128.65, 128.87, 129.06, 129.40, 130.73, 131.54,
135.67, 137.54, 138.29, 146.11.
after
treating
H2SO4
(Scheme
1).
2-(4-isopropylphenyl)-4,5-diphenyl-1H-imidazole (3j); white
solid; m.p.: 254ꢀ256 °C, Lit.23m.p.: 253ꢀ255 °C; IR(KBr) / ν
(cmꢀ1): 3422 (NꢀH), 3054 (C=CꢀH), 2960 (CꢀCꢀH), 1493
1
(C=N), 1446, 1603 (C=C aromatic); H NMR (DMSOꢀd6, 400
MHz) δ (ppm): 1.22ꢀ1.23 (d, 6H, J=6.4 Hz, 2Me), 2.92ꢀ2.93
(m, 1H, CH),7.20ꢀ7.22 (d, 2H,J=8, HꢀAr), 7.28ꢀ7.54 (m, 10H,
HꢀAr), 7.97ꢀ7.99(d, 2H, J=8, HꢀAr), 12.57(s, 1H, NH); 13C
NMR(DMSOꢀd6, 100MHz) δ (ppm): 24.23, 33.72, 125.75,
126.94, 127.06, 127.55, 128.16, 128.41, 128.51, 128,64,
128.86, 129.11, 131.59, 135.69, 137.42, 146.18, 149.06.
2-(2-chlorophenyl)-4,5-diphenyl-1H-imidazole (3k)
;
light
bisque solid; m.p.: 196ꢀ199 °C, Lit.24m.p.: 199ꢀ201 °C;
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N
indicate a crystallized structure at 2θ: 30.1°, 35.67°, 43.42°, 53.88°,
Cl-
N
57.38° and 62.95°, which are assigned to the (220), (311), (400),
N
26
H3CO
H3CO
N
H3CO
H3CO
H3CO
3
(422), (511) and (440) crystallographic faces of magnetite
.
Si
3
Si
Cl
N
N
N
Characteristic peak of SiO2 in core shell structure has been hidden
under weak peak of Fe3O4 at 2θ=30° 27. The average diameter for
Fe3O4@SiO2.HM.SO3H was about 55 nm and the average core
diameter was calculated to be about 21 nm from XRD results by
DebyeꢀScherer equation.
H3CO
N
O
O
S
O
3
-O3S
4
N
Cl-
H3CO
H3CO Si
H3CO
HO3S
-
N
SO3
N
N
4
4
N
Cl-
SiO2
Fe3O4
4
-O3S
N
SO3H
N
Si
N
4
1) Fe3O4@SiO2
2) H2SO4
4
HO3S
-
HSO4
3
Scheme 1. Different steps for the synthesis of Fe3O4@SiO2.HM.SO3H
3.2. Characterization of catalyst Fe3O4@SiO2.HM.SO3H
The catalyst was characterized using FE SEM, XRD, FTꢀIR and
VSM.Successful functionalization of the MNPs can be characterized
by FTꢀIR spectra. Figure 1 shows the FTꢀIR spectrum of the catalyst
and ionic liquid. The presence of FeꢀO stretching vibration is
inferred from the peak near 635 cmꢀ1, OꢀH stretching vibration near
3366 cmꢀ1 and OꢀH deformation vibration near 1628 cmꢀ1. Peaks of
(SiꢀO) stretching are around 1090 cmꢀ1. At about 1207 cmꢀ1 and 1136
cmꢀ1, S=O stretching was appeared and the CꢀN stretching bond is
about 1000ꢀ1350 cmꢀ1.
Fig 2. XRD patterns of (a) Fe3O4@SiO2.HM.SO3H, (b) Fe3O4@SiO2, (c)
Fe3O4.
Figure 3 shows the FE SEM image of Fe3O4@SiO2.HM.SO3H,
in that the cubic morphology with an average diameter of about
60 nm for catalyst was observed.
500nm
Fig 1. FTꢀIR spectrums of (a) Fe3O4@SiO2.HM.SO3H, (b) HM.SO3H (IL)
The Xꢀray diffraction patterns of Fe3O4, Fe3O4@SiO2 and
Fe3O4@SiO2.HM.SO3H, are shown in Figure 2. The positions and
relative intensities of all the peaks in the XRD pattern of Fe3O4,
indicating retention of the crystalline cubic spinel structure during
functionalization of the MNPs 25. The patterns in both catalysts
Fig 3. FESEM of Fe3O4@SiO2.HM.SO3H
The components of the catalyst were analyzed by using energy
dispersive spectroscopy (EDX). The EDX spectrum in Figure 4
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shows the elemental composition (S, O, N, C, Si and Fe) of the
catalyst.
3.3. Investigation of catalytic activity for synthesis of 2,4,5-
trisubstituted imidazoles
The acidity of the catalyst was measured by an acidꢀbase
titration.The pH was calculated to be approximately 1.The
efficiency of the supported catalyst was found to be solvent
independent and without any solvent good yields observed.
3.3.1. Optimization of the microwave power
Power of the microwave instrument was optimized and the best
operating power was found to be 450 watt.
Table1. Microwave power optimizationa, b
Entry
Power (w)
Time (min)
Yield (%)
1
2
3
4
5
6
180
360
450
600
650
700
7
7
7
7
7
7
45
70
91
84
83
78
Fig 4. EDX of Fe3O4@SiO2.HM.SO3H
a Reaction condition: benzil (1 mmol), 3,4ꢀdimethoxy
benzaldehyde (1 mmol), NH4OAc (2 mmol)
b amount of catalyst (30 mg)
Magnetic properties of catalyst and Fe3O4@SiO2 nanoparticles were
determined by VSM at room temperature (Figure 5). Magnetization
of samples could be completely saturated at high fields of up to 1.0 T
and the saturation magnetization of samples changed from 47 to 7
emu gꢀ1, because of the functionalization by ionic liquid. Moreover,
the room temperature magnetization curves, before and after
3.3.2. Optimization reactions of catalyst amount
The reaction has been done in the presence of different catalyst
amounts under optimized power.
functionalization exhibit no hysteresis which demonstrates its super
27,
paramagnetic characteristic
28. The strong magnetization of the
Table 2. Optimization of the catalyst amounta
Amount of
catalystwas also revealed by simple attraction with an external
magnet.
Entry
Time (min)
Yield (%)
catalyst (g)b
1
2
3
4
5
6
0.010
15
10
7
42
77
91
87
87
85
0.020
0.030
0.040
7
0.045
7
0.050
7
a Benzil (0.5mmol), 3,4ꢀdimethoxy benzaldehyde (0.5mmol),
NH4OAc (1mmol), microwave power 450 W.
b The amount of Fe3O4@SiO2.HM.SO3H
After optimizing the reaction conditions, it was used different
benzaldehydes as the substrates for this reaction. The results are
summarized in Table 3. As the entries in Table 3 show, the
catalysis proceeded well for a wide variety of aldehydes,
providing the corresponding imidazoles in high yields and short
reaction times.
Fig 5. VSM of (a) Fe3O4@SiO2, (b) Fe3O4@SiO2.HM.SO3H
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Scheme 2. Synthesis of 2,4,5ꢀtrisubstituted imidazoles from benzil, benzaldehyde and NH4OAc
Table 3. Synthesis of 2,4,5ꢀtrisubstituted imidazoles in the presence of catalyst Fe3O4@SiO2.HM.SO3H a
Entry
Benzaldehyde
Product
Time (min)
8
Yield(%)b
77
1
2a
3a
3b
2
3
4
7
7
8
85
90
87
2b
2c
3c
2d
3d
MeO
OMe
H
N
Ph
Ph
5
6
7
7
8
7
89
80
85
N
3e
3f
2e
2f
3g
3h
2g
2h
8
9
7
8
85
76
2i
3i
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10
11
8
7
93
84
3j
2j
2k
3k
12
13
7
7
89
85
2l
3l
2m
3m
14
7
90
3n
2n
a.Reaction condition: benzil (1 mmol), 3,4ꢀdimethoxy benzaldehyde (1 mmol), NH4OAc (2 mmol) was under microwave irradiation (power 450 w) and solvent
free condition, Catalyst amount: 30 mg.
b Isolated product yields
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CHO
NH3
Ph
O
O
Ph
Ph
O
H
NH
Ph
Ph
(A)
NH
(B)
NH3
H+
HO
Ph
N
Ph
H
N
Ph
Ph
Ph
Ph
NH
N
(C)
Ph
OH
Ph
N
Ph
NH
H
+HN
Ph
Ph
Ph
N
H+
HO3S
4
N
Cl-
SiO2
Fe3O4
N
SO3H
N
Si
N
4
4
HO3S
-
HSO4
3
Scheme 4. Proposed mechanism of the reaction
Conclusions
The reusability of the catalyst is an important benefit for
catalytic reactions. The reusability was investigated using
the reaction of benzil, 3,4ꢀdimethoxy benzaldehyde and
NH4OAc in the presence of Fe3O4@SiO2.HM.SO3H under
optimized conditions (Figure 6).The catalyst was recovered
by an external magnet and washed thrice with acetone, dried
and then reused for subsequent reactions for at least 5 times
with less reduction in its catalytic activity.
A novel ionic liquid coated nano magnetite catalyst was
synthesized and tested as a reusable nano catalyst in the oneꢀpot
three component reaction of benzil, benzaldehyde and NH4OAc
under microwave irradiation and neat condition to give 2,4,5ꢀ
trisubstituted imidazoles. Excelling features of the proposed
methodology include high efficiency, reusability, short times of
reaction, high yields of products and simplicity, making it an
attractive alternative for the clean synthesis of 2,4,5ꢀtrisubstituted
imidazoles as biologically and pharmaceutically relevant
material.
90
90
90
88
86
100
80
60
40
20
0
85
Acknowledgements
The authors are grateful to University of Kashan for supporting
this work by Grant No. 159148/47.
1
2
3
4
5
6
References:
Fig 6.Reusability of catalyst for the synthesis of 2,4,5ꢀtrisubstituted
imidazoles
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Graphical abstract
A simply, highly versatile and efficient synthesis of 2,4,5-trisubstituted imidazoles catalyzed
by Fe3O4@SiO2.HM.SO3H is achieved via three component one pot reaction of benzil,
benzaldehyde and NH4OAc.