A highly efficient magnetic solid acid catalyst for synthesis of 2,4,5-trisubstituted imidazoles under ultrasound irradiation

Article abstract of DOI:10.1016/j.ultsonch.2012.10.004

Fe₃O₄ nanoparticles were prepared by chemical coprecipitation method and subsequently coated with 3-aminopropyltriethoxysilane (APTES) via silanization reaction. Grafting of chlorosulfuric acid on the amino-functionalized Fe₃O₄ nanoparticles afforded sulfamic acid-functionalized magnetic nanoparticles (SA-MNPs). SA-MNPs was found to be a mild and effective solid acid catalyst for the efficient, one-pot, three-component synthesis of 2,4,5-trisubstituted imidazoles under ultrasound irradiation. This protocol afforded corresponding imidazoles in shorter reaction durations, and in high yields. This green procedure has many obvious advantages compared to those reported in the previous literatures, including avoiding the use of harmful catalysts, easy and quick isolation of the products, excellent yields, short routine, and simplicity of the methodology.

Full text of DOI:10.1016/j.ultsonch.2012.10.004

Ultrasonics Sonochemistry 20 (2013) 740–746
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Ultrasonics Sonochemistry
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A highly efficient magnetic solid acid catalyst for synthesis of 2,4,5-trisubstituted
imidazoles under ultrasound irradiation
⇑
Javad Safari , Zohre Zarnegar
Laboratory of Organic Compound Research, Department of Organic Chemistry, College of Chemistry, University of Kashan, P.O. Box: 87317-51167 Kashan, Islamic Republic of Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 August 2012
Received in revised form 29 September 2012
Accepted 9 October 2012
Available online 17 October 2012
Fe3O4 nanoparticles were prepared by chemical coprecipitation method and subsequently coated with
3-aminopropyltriethoxysilane (APTES) via silanization reaction. Grafting of chlorosulfuric acid on the
amino-functionalized Fe3O4 nanoparticles afforded sulfamic acid-functionalized magnetic nanoparticles
(SA-MNPs). SA-MNPs was found to be a mild and effective solid acid catalyst for the efficient, one-pot,
three-component synthesis of 2,4,5-trisubstituted imidazoles under ultrasound irradiation. This protocol
afforded corresponding imidazoles in shorter reaction durations, and in high yields. This green procedure
has many obvious advantages compared to those reported in the previous literatures, including avoiding
the use of harmful catalysts, easy and quick isolation of the products, excellent yields, short routine, and
simplicity of the methodology.
Keywords:
Fe3O4 nanoparticles
Sulfamic acid
Imidazole
Solid acid catalyst
Ultrasound irradiation
Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction
and play important roles in biochemical processes [8–10]. A num-
ber of methods have been developed for the synthesis of 2,4,5-tri-
During the past decades, advances in nanoscience and nanotech-
nology have pushed forward the synthesis of functional magnetic
nanoparticles (MNPs), which is one of the most active research
areas in advanced materials. MNPs that have unique magnetic prop-
erties and other functionalities have enabled a wide spectrum of
applications [1]. Iron oxide magnetic nanoparticles (Fe3O4-MNPs)
are approximately 20–30 nm in size containing a single magnetic
domain with a single magnetic moment and exhibit superparamag-
netism [2]. Surface functionalized iron oxide magnetic nanoparti-
cles (MNPs) are a kind of novel functional materials, which have
been widely used in biotechnology and analysis. Magnetic nanocat-
alysts can easily be separated and recycled from the products by an
external magnet. Moreover, their catalytic performance is en-
hanced, for the available surface area of the nonporous MNPs is
external and the internal diffusion is practically avoided [3].
On the other hand, solid acid catalysts such as clays, zeolites,
sulfated metal oxides or carbons and heteropolyacids have already
attracted extensive research interests [4–7]. Among these solid
acid catalysts, magnetically recyclable nanocatalyst systems, are
unique due to simple work-up procedure, ease of separation, and
higher catalytic activity, etc. [1,3].
substituted imidazoles. Several methods are used for synthesis of
multi-substituted imidazoles [11–22]. Recently, one-pot condensa-
tions of an aldehyde and ammonium acetate with an
a-hydroxy
ketone, an -keto oxime, or a 1,2-diketone have been achieved
a
by using a variety acid catalysts, for example silica sulfuric acid
[23,24], boric acid [25], phosphomolybdic acid [26], H2SO4 [27],
H3PO4 [28], oxalic acid [29], p-toluenesulfonic acid [30].
Despite their potential utility, some of these methods are not
environmentally friendly and suffer from one or more disadvan-
tages, for example hazardous reaction conditions, complex work-
up and purification, strongly acidic conditions, high temperature,
poor yields, occurrence of side reactions, and long reaction time.
Therefore, the development of a mild general method to overcome
these shortcomings remains a challenge for organic chemists in the
synthesis of highly substituted imidazoles [10,31].
During the last three decades, ultrasound-accelerated organic
chemical reactions have been increasingly developed by research-
ers across the globe for the synthesis of organic molecules. Ultra-
sound irradiation offers an alternative energy source for organic
reactions which are ordinarily accomplished by heating. Ultra-
sound- assisted reactions proceed by the formation, growth and
collapse of acoustic bubbles in the reaction medium. These directly
help in shortening the time span of reactions and increasing the
yield of products [32].
Imidazole derivatives are a very interesting class of heterocyclic
compounds because they have many pharmacological properties
In this study, we report immobilization of sulfamic acid groups
on the magnetic Fe3O4 nanoparticles, as a new heterogeneous
⇑
Corresponding author. Tel.: +98 3615912320; fax: +98 361 5912397.
E-mail address: Safari@kashanu.ac.ir (J. Safari).
1350-4177/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ultsonch.2012.10.004

J. Safari, Z. Zarnegar / Ultrasonics Sonochemistry 20 (2013) 740–746
741
chloride gas evolved from the reaction vessel immediately. Then,
the as prepared functionalized MNPs nanoparticles were separated
by magnetic decantation and washed three times with dry CH2Cl2
to remove the unattached substrates.
2.3. General procedure for the synthesis of 2,4,5-trisubstituted
imidazoles under silent condition
A mixture of benzil (1 mmol), aldehyde (1 mmol), ammonium
acetate (0.4 g, 5 mmol) and SA-MNPs (0.1 g) in 10 ml ethanol was
taken in a 50 ml flask and the reaction mixture was stirred under
reflux conditions. After the completion of the reaction (monitored
by TLC), the reaction was allowed to cool and the catalyst was sep-
arated by an external magnet. The reaction mixture was concen-
trated on a rotary evaporator under reduced pressure and the
solid product obtained was dissolved in acetone and filtered. The
product was washed with water and recrystallized from acetone–
water 9:1 (v/v) to produce the desired product 5a as white solid
in 90% yield.
Scheme 1. One-pot synthesis of 2,4,5-trisubstituted imidazoles catalyzed by SA-
MNPs under ultrasound irradiation at ambient temperature.
catalyst for the synthesis of trisubstituted imidazoles via one-pot
condensation of 1,2-diketone 1 with aldehyde 2 and NH4OAc under
ultrasound irradiation (Scheme 1). This method is an efficient and
rapid ultrasonic assisted route for the synthesis of a range of tri-
substituted imidazoles.
2. Experimental
2.4. General procedure for the synthesis of 2,4,5-trisubstituted
imidazoles ultrasonic irradiation
2.1. Chemicals and apparatus
Chemical reagents in high purity were purchased from the
Merck Chemical Company. All materials were of commercial re-
agent grade. Melting points were determined in open capillaries
using an Electrothermal Mk3 apparatus and are uncorrected. 1H
NMR and 13C NMR spectra were recorded with a Bruker DRX-400
spectrometer at 400 and 100 MHz respectively. NMR spectra were
obtained in DMSO-d6 solutions and are reported as parts per mil-
lion (ppm) downfield from tetramethylsilane as internal standard.
The abbreviations used are: singlet (s), doublet (d), triplet (t) and
multiplet (m). FT-IR spectra were obtained with potassium bro-
mide pellets in the range 400–4000 cmꢀ1 with a Perkin–Elmer
550 spectrometer. A mass spectrum was recorded by a QP-
1100EX Shimadzu spectrometer. The element analyses (C, H, N)
were obtained from a Carlo ERBA Model EA 1108 analyzer carried
out on Perkin–Elmer 240c analyzer. The UV–vis measurements
were obtained with a GBC cintra 6 UV–vis spectrophotometer.
Nanostructures were characterized using a Holland Philips Xpert
X-ray powder diffraction (XRD) diffractometer (CuK, radiation,
k = 0.154056 nm), at a scanning speed of 2°/min from 10° to 100°
(2h). Scanning electron microscope (SEM) was performed on a FEI
Quanta 200 SEM operated at a 20 kV accelerating voltage. The sam-
ples for SEM were prepared by spreading a small drop containing
nanoparticles onto a silicon wafer and being dried almost com-
pletely in air at room temperature for 2 h, and then were trans-
ferred onto SEM conductive tapes. The transferred sample was
coated with a thin layer of gold before measurement. Sonication
was performed in Shanghai Branson-BUG40-06 ultrasonic cleaner
(with a frequency of 35 kHz and a nominal power 200 W) esti-
mated calorimetrically [33]. A circulating water bath (DC2006,
Shanghai Hengping Apparatus Factory) with an accuracy of 0.1 K
was adopted to keep the reaction temperature at a constant.
A 25 mL Erlenmeyer flask was charged with benzil (1 mmol),
aldehyde (1 mmol), ammonium acetate (0.4 g, 5 mmol), SA-MNPs
(0.1 g) and ethanol (10 mL). The reaction flask was located in the
ultrasonic bath, where the surface of reactants is slightly lower
than the level of the water, and irradiated under 20, 40, 60, 80
and 100% of the power of the ultrasonic bath and the temperature
inside the reactor at 40 °C for the period of time (The reaction was
monitored by TLC) separately as indicated in Table 4. After the
reaction was completed, the catalyst was separated by an external
magnet and reused as such for the next experiment. The reaction
mixture was concentrated on a rotary evaporator under reduced
pressure and the solid product obtained was dissolved in acetone
and filtered. The solid product obtained was washed with water
and recrystallized from acetone–water 9:1 (v/v) to offer pure prod-
uct 3a in 98% yield. All products were known and characterized by
comparison of their physical and spectra data with those already
reported [31].
2.5. Spectroscopic data of selected compounds
2-(3-Nitrophenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole (3o).
Yellow solid. IR (KBr) (t
max/cmꢀ1): 3428 (NH), 1615 (C=C), 1523
(C=N), 1460 (N=O), 1348 (N–O), 1249 (C–O); 1H NMR (400 MHz,
DMSO-d6): dH 12.92 (s, 1H, NH), 8.92 (s, 1H, Ar–H), 8.50 (d, 1H,
J = 8.2 Hz, Ar–H), 8.20 (d, 1H, J = 8.2 Hz, Ar–H), 7.75 (t, 1H,
J = 8.2 Hz, Ar–H), 7.47 (d, 2H, J = 8.4 Hz, Ar–H), 7.43 (d, 2H,
J = 8.4 Hz, Ar–H), 7.00 (d, 2H, J = 8.4 Hz, Ar-H), 6.90 (d, 2H,
J = 8.4 Hz, Ar–H), 3.80 (s, 3H, OMe), 3.75 (s, 3H, OMe) ppm; 13C
NMR (100 MHz, DMSO-d6): dC 159.4, 158.6, 148.8, 143.1, 137.5,
132.5, 131.4, 130.8, 130.2, 128.8, 128.7, 127.9, 123.5, 122.7,
119.7, 114.6, 114.1, 55.7, 55.5 ppm; Anal. Calcd. for C23H19N3O4:
C, 68.82; H, 4.77; N, 10.47%. Found: C, 68.79; H, 4.75; N, 10.44%.
2-(3-methoxyphenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole
2.2. Preparation of solid acid catalyst
(3p). White solid. IR (KBr) (t
max/cmꢀ1): 3430 (N–H), 1608 (C=C),
Fe3O4-MNPs were prepared using chemical coprecipitation de-
scribed in the literature [34] and subsequently were coated with
3-aminopropyltriethoxysilane to achieve aminofunctionalized
magnetic nanoparticles APTES-MNPs [35]. Sulfamic acid-function-
alized magnetic Fe3O4 nanoparticles was prepared by means of a
procedure reported elsewhere [3]. In short, The APTES-MNPs
(500 mg) were dispersed in dry CH2Cl2 (3 ml) by ultrasonic bath
for 10 min. Subsequently, chlorosulfuric acid (1 ml) was added
dropwise over a period of 30 min at room temperature. Hydrogen
1519 (C=N), 1246 (C–O); 1H NMR (400 MHz, DMSO-d6): dH 12.50
(s, 1H, NH), 7.64 (d, 1H, J = 8.0 Hz, Ar–H), 7.62 (s, 1H, Ar–H),
7.36–7.46 (m, 5H, Ar–H), 7.00 (d, 2H, J = 8.4 Hz, Ar–H), 6.91 (dd,
1H, J = 8.4, 2.2 Hz, Ar–H), 6.87 (d, 2H, J = 8.4 Hz, Ar–H), 3.82 (s,
3H, OMe), 3.79 (s, 3H, OMe), 3.74 (s, 3H, OMe) ppm; 13C NMR
(100 MHz, DMSO-d6): dC 160.0, 158.9, 158.2, 145.1, 136.2, 132.3,
130.2, 130.2, 128.6, 128.2, 127.2, 124.1, 117.0, 115.5, 114.4,
114.3, 110.5, 55.6, 55.5, 55.5 ppm; Anal. Calcd. for C24H22N2O3: C,
74.59; H, 5.74; N, 7.25%. Found: C, 74.58; H, 5.75; N, 7.24%.

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J. Safari, Z. Zarnegar / Ultrasonics Sonochemistry 20 (2013) 740–746
5-[4,5-Bis(4-methoxyphenyl)-1H-imidazol-2-yl]-2- methoxyphe-
nol (3q). Ash-gray solid. IR (KBr) (
t
max/cmꢀ1): 3424 (N–H), 3320
(O–H), 1615 (C=C), 1504 (C=N), 1249 (C–O); 1H NMR (400 MHz,
DMSO-d6): dH 12.26 (s, 1H, NH), 9.11 (s, 1H, OH), 7.52 (s, 1H, Ar–
H), 7.37–7.46 (m, 6H, Ar–H), 6.98 (d, 2H, J = 8.4 Hz, Ar–H), 6.86
(d, 2H, J = 8.4 Hz, Ar–H), 3.80 (s, 3H, OMe), 3.78 (s, 3H, OMe),
3.73 (s, 3H, OMe) ppm; 13C NMR (100 MHz, DMSO-d6): dC 159.1,
158.7, 148.4, 146.9, 145.6, 129.8, 129.2, 128.4, 126.3, 126.0,
123.5, 124.1, 116.8, 114.3, 114.0, 113.2, 112.5, 56.1, 55.5,
55.1 ppm; Anal. Calcd. for C24H22N2O4: C, 71.63; H, 5.51; N,
6.96%. Found: C, 71.61; H, 5.49; N, 6.95%.
3. Results and discussion
3.1. Characterization of SA-MNPs as solid acid catalyst
The magnetite nanoparticles of 18–20 nm were prepared by
coprecipitation of iron(II) and iron(III) ions in basic solution at
85 °C using the method described by Massart [34]. For the surface
modification, the magnetic nanoparticles coated with 3-aminopro-
pyltriethoxysilane (APTES) to achieve aminofunctionalized mag-
netic nanoparticles. Ultimately, the reaction of amino groups
with chlorosulfuric acid led to sulfamic acid-functionalized mag-
netic Fe3O4 nanoparticles (SA-MNPs) (Scheme 2).
Fig. 1. XRD patterns of (a) MNPs, (b) APTES–MNPs and (c) SA-MNPs.
0:94k
b cos h
The number of H+ sites of SA-MNPs was determined by pH-ISE
conductivity titration (Denver Instrument Model 270) and found to
be 1.25 H+ sites per 1 g of solid acid at 25 °C (pH 2.30). Titration
carried out under sonication and the number of available H+ is
the same under the silence and the sonication, however, the tem-
perature must be constant. Like any other equilibrium constant,
the value of Kw for H2O varies with temperature. Its value is usually
taken to be 1.00 ꢁ 10ꢀ14 mol2 dmꢀ6 at room temperature. Fig. 1
presents the XRD-diffraction patterns of the prepared Fe3O4-MNPs,
APTES–MNPs, and SA-MNPs. The position and relative intensities
of all peaks confirm well with standard XRD pattern of Fe3O4
(JCPDS card No. 79-0417) indicating retention of the crystalline cu-
bic spinel structure during functionalization of MNPs. The XRD pat-
terns of the particles show six characteristic peaks reveal a cubic
iron oxide phrase (2h = 30.35, 35.95, 43.45, 53.70, 57.25, 62.88,
71.37, 74.46). These are related to their corresponding indices
(220), (311), (400), (331), (422), (333), (440) and (531), respec-
tively [34]. It is implied that the resultant nanoparticles are pure
Fe3O4 with a spinel structure and that the grafting process did
not induced any phase change of Fe3O4. A weak broad band
(2h = 18–27°) appeared in the the SA-MNPs which could be as-
signed to the amorphous silane shell formed around the magnetic
cores [36].
DðhklÞ ¼
where D(hkl) is the average crystalline diameter, 0.94 is the
Scherrer’s constant, k is the X-ray wavelength, b is the half width
of XRD diffraction lins and h is the Bragg’s angle in degree. Here,
the (311) peak of the highest intensity was picked out to evaluate
the particle diameter of the nanoparticles. MNPs and SA-MNPs were
calculated to be 18 nm and 20 nm, respectively. Fig. 2 shows the
Fourier transform infrared (FTIR) spectra of both the unfunctional-
ized and functionalized magnetic nanoparticles. The Fe–O stretch-
ing vibration near 580 cmꢀ1
, O–H stretching vibration near
3432 cmꢀ1 and O–H deformed vibration near 1625 cmꢀ1were ob-
served for both in Fig. 2(a) and (b). The significant features observed
for Fig. 2(b) are the appearance of the peaks at 1002 cmꢀ1 (Si–O
stretching) and at 2800 cmꢀ1 (–CH2 stretching). The peak at
3423 cmꢀ1 in Fig. 2(b) was probably attributed to the free amino
groups, which is overlapped by the O–H stretching vibration. These
Scheme 2. Preparation steps for fabricating sulfamic acid-functionalized magnetic
Fig. 2. The comparative FT-IR spectra for (a) MNPs, (b) APTES–MNPs and (c) SA-
Fe3O4 nanoparticles.
MNPs.

J. Safari, Z. Zarnegar / Ultrasonics Sonochemistry 20 (2013) 740–746
743
sample indicate
a
saturation magnetization value (Ms) of
52.3 emu gꢀ1, lower than that of bare magnetic nanoparticles
(60.7 emu gꢀ1) due to the coated shell. In Fig. 4 we can also see that
the two magnetization curves both follow a Langevin behavior
over the applied magnetic field and the coercivity (HC) could be
ignored, which can be considered as superparamagnetism [37].
The sulfamic acid-functionalized magnetic Fe3O4 nanoparticles
could be separated to the sidewall of the container after 30 s. using
a magnet of 2000 Gs, suggesting the obtained magnetic micro-
spheres had an excellent magnetic responsivity, which prevents
composite microspheres from aggregation and enables them to
redisperse rapidly when the magnetic field is removed.
The SEM image shows that magnetite (Fe3O4) particles have a
mean diameter of about 18 nm and a nearly spherical shape in
Fig. 4(a) and (b) shows that APTES–MNPs particles still keep the
morphological properties of Fe3O4 except for a slightly larger parti-
cle size and smoother surface, which silica are uniform coated on the
Fe3O4 particles to form silica shell. Compared to the APTES–MNPs,
The SEM image shown in Fig. 4(c) demonstrates that SA-MNPs nano-
particles are nearly spherical with more than 20 nm in size.
Fig. 3. Magnetization curves for the prepared MNPs and SA-MNPs at 40 °C.
results provided the evidences that the amino groups were success-
fully attached to the surface of Fe3O4 nanoparticles [37]. Reaction of
APTES–MNPs with chlorosulfuric acid produces SA-MNPs in which
the presence of sulfonyl moiety is asserted with 1217 and
1124 cmꢀ1 bands in FT-IR spectra [3].
3.2. Evaluation of the catalytic activity of SA-MNPs through the
synthesis of 2,4,5-trisubstituted imidazoles
The magnetization curve for Fe3O4 nanoparticles and SA-MNPs
is shown in Fig. 3. Room temperature specific magnetization (M)
versus applied magnetic field (H) curve measurements of the
To achieve suitable conditions for the synthesis of 2,4,5-trisub-
stituted imidazoles, various reaction conditions have been investi-
gated in the reaction of 4-methoxybenzaldehyde 2b, benzil 1a, and
Fig. 4. The SEM image of (a) MNPs, (b) APTES-MNPs and (c) SA-MNPs.

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J. Safari, Z. Zarnegar / Ultrasonics Sonochemistry 20 (2013) 740–746
Table 3
The effect of intensity power of ultrasonic on the synthesis of 3b.
Max power
20%
40%
60%
80%
100%
intensity (W)
(40 W)
(80 W)
(120 W)
(160 W)
(200 W)
Time (min) Yields 40 (85)
(%)
35 (92)
30 (97)
30 (90)
30 (87)
b
Isolated yields.
Scheme 3. Standard model reaction.
the rate power of the ultrasonic bath (40, 80, 120, 160 and
200 W). The results were showed in Table 3. The intensity of son-
ication is proportional to the amplitude of vibration of the ultra-
sonic source and, as such, an increment in the amplitude of
vibration will lead to an increase in the intensity of vibration and
to an increase in the sonochemical effects. Increase of ultrasonic
powerled to relatively higher yield and shorter reaction time be-
fore the ultrasound power intensity reached 60%, and then the
yield decreased slightly with increasing ultrasound power inten-
sity. Generally, The increase in the acoustic power could increase
the number of active cavitation bubbles and also the size of the
individual bubbles. Both increases can be expected to result in an
increase in the maximum collapse temperature [40], and the
respective reaction could be accelerated.
Moreover, when ultrasonic intensity exceeded the optimal va-
lue, a large number of gas bubbles exist in the solution and a lesser
level of energy is focused on the reaction vessel because of the
scattering effect of gas bubbles on the sound waves. The use of high
ultrasonic intensity does not always lead to good results. On the
other hand, it is possible the coalescence of the cavities in the pres-
ence of large number of cavities resulting in the formation of a
large cavity which collapses less violently. So with the inordinate
increase in the operating intensity, the utilization efficiency of
ultrasound would decrease and the reaction yield decreased too
[41].
Using the optimized reaction conditions, this process was dem-
onstrated by the wide range of substituted and structurally divers
aldehydes to synthesize the corresponding products in high to
excellent yields (Table 4, method A). Aldehydes bearing either elec-
tron-withdrawing or electron-donating groups perform equally
well in the reaction and all imidazoles were obtained in high
yields. For more examination of the influence of ultrasound irradi-
ation in this transformation, comparison of the reaction under two
methods, ultrasound irradiation at 40 °C (method A) and reflux
conditions (method B) was performed. As illustrated in Table 4,
method A in comparison with method B is better in both yields
and especially in the reaction times (see Table 4).
ammonium acetate as a model reaction (Scheme 3). We examined
the effect of different solvents such as EtOH, MeOH, THF, DMF,
CH3CN, and DCM on a model reaction under ultrasound irradiation
(power intensity: 40%) at 40 °C. The results were summarized in
Table 1. The use of 0.008 g of SA-MNPs in ethanol afforded a 86%
yield (Table 1, entry 1) of the desired product. Therefore EtOH
was chosen as solvent of reaction.
After this, the reaction was performed in the presence of 0.005,
0.008, 0.1, 0.12 and 0.15 g of SA-MNPs (Table 2) with and without
ultrasonic irradiation. In all cases, the experimental results shows
that the reaction times are shorter and the yields of the products
are higher under sonication. The reason may be the phenomenon
of cavitation produced by ultrasound. Cavitation is the origin of
sonochemistry, a physical process that creates, enlarges, and im-
plodes gaseous and vaporous cavities in an irradiated liquid, thus
enhancing the mass transfer and allowing chemical reactions to oc-
cur. Applying ultrasound, compression of the liquid is followed by
rarefaction (expansion), in which a sudden pressure drop forms
small, oscillating bubbles of gaseous substances. these bubbles
are small and rapidly collapse, they can be seen as microreactors
that offer the opportunity of speeding up certain reactions and also
allow mechanistically novel reactions to take place in an absolutely
safe manner [32,38,39]. The best results were obtained using 0.1 g
of the catalyst under both conditions (Table 2, entry 4). As shown,
in the absence of catalyst the yield of the product was found to be
low (Table 2, entry 1).
In order effect of intensity power of ultrasonic on reaction, the
reaction was also performed at 20%, 40%, 60%, 80% and 100% of
Table 1
Screening of solvent effect on model reaction.a
Entry
Solvent
Time (min)
Yield (%)b
1
2
3
4
5
6
Ethanol
Methanol
DCM
DMF
THF
30
30
30
30
30
30
86
60
15
32
35
48
Acetonitril
A plausible mechanism for the formation of trisubstituted imi-
dazoles is envisaged in Scheme 4. A plausible mechanism for
these reactions is that aldehyde and 1,2-diketone are first acti-
vated by SA-MNPs (H+) to afford A and B respectively. Then, imine
intermediate (A), condenses further with the carbonyl carbon of
1,2 diketone imine (B) and formation of carbocation (C) followed
by attack imine nitrogen to positive center and dehydration to af-
ford the iso-imidazole (E), which rearranges via [1,5] sigmatropic
shift to the required imidazole (Scheme 4). The reaction mecha-
nism involves a polar transition state starting from a neutral
ground state, that under ultrasonic irradiation ionic reactions
are accelerated by physical effects – better mass transport, Typi-
cally, in a heterogeneous solid/liquid system, the collapse of the
cavitation bubble results in significant structural and mechanical
defects. Collapse near the surface produces an asymmetrical in-
rush of the fluid to fill the void forming a liquid jet targeted at
the surface. This effect is equivalent to high-pressure/high-velocity
liquid jets. These jets activate the solid catalyst and increase the
mass transfer to the surface by the disruption of the interfacial
a
Reaction of benzil, 4-methoxybenzaldehyde and ammonium acetate (1:1:5) in
presence of SA-MNPs (0.008) as a catalyst under ultrasonic irradiation with power
intensity of 40% at 40 °C.
b
Isolated yield based on aldehyde.
Table 2
Comparison of reaction time and yields with or without sonication for the synthesis of
3b product.
Entry
Catalyst (g)
With sonicationa
Without sonicationb
Yield (%)
Time (min)
Yield (%)
Time (min)
1
2
3
4
5
6
0
10
50
70
92
92
93
35
35
35
35
35
45
15b(5)a
30b
180
180
180
180
180
210
0.005
0.008
0.1
0.12
0.15
72b
90b
90b
92b
a
Under ultrasonic waves (power intensity: 40%) at 40 °C.
Reflux condition.
b

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745
Table 4
One-pot synthesis of 2,4,5-trisubstituted imidazoles catalyzed by SA-MNPs in EtOH under ultrasound irradiation at 40 °C (method A) and reflux conditions (method B)a.
Entry
Benzil
R1, R2
Aldehyde
R3
Productb
Method A time (min)/yield (%)c
Method B time (min)/yield (%)c
mprep/mplit. (°C)
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1c
1c
H
H
H
H
H
H
H
H
2a
2b
2c
2d
2e
2f
2g
2
2i
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
3a
3b
3c
3d
3e
b
b
3h
3i
25/98
30/97
35/90
30/95
30/93
30/92
30/93
30/97
30/95
35/97
45/95
40/92
35/95
35/92
35/94
35/97
35/98
35/94
25/98
25/96
120/9o
180/89
150/84
150/92
150/90
150/91
120/93
120/94
120/92
130/91
180/80
180/90
160/87
160/85
160/87
160/89
140/91
140/92
90/95
(271–273)/(270–272)31
(230–231)/(228–231)31
(229–232)/(230–233)31
(302–304)/(301–303)31
(260–261)/25931
p-OMe
p-Me
m-Br
m-OH
m-NO2
(268–270)/(269–271)31
(258–260)/(259–262)31
(215–216)/(214–216)31
(255–257)/(256–257)32
(202–204)/(201–203)31
(184–186)/(183–185)31
(187–189)/(186–188)31
(250–252)/(248–251)31
(229–231)/(230–232)31
(242–244)/(240–242)32
(235–236)/(234–236)31
(131–133)/(132–134)31
(194–196)/(195–197)31
(249–250/(248–250)10
(272–274)/(271–273)10
m-OMe
m-OH, p-OMe
m-OMe, m-OMe
H
p-OMe
p-Me
9
H
10
11
12
13
14
15
16
17
18
19
20
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
F
3j
3k
3l
m-Br
m-OH
3m
3n
3o
3p
3q
3r
3s
3t
m-NO2
m-OMe
m-OH, p-OMe
m-OMe, m-OMe
m-OH, p-OMe
m-Br
2h
2d
F
70/85
a
b
c
Benzil (1 mmol), Aldehyde (1 mmol), NH4OAc (5 mmol), SA-MNPs (0.1 g).
All products were characterized by 1H NMR, 13C NMR, IR and MS spectra.
Isolated yields.
boundary layers as well as dislodging the material occupying the
inactive sites. Collapse on the surface, produces enough energy to
cause fragmentation. Thus, in this situation, ultrasound can
increase the surface area for a reaction and provide additional
activation through efficient mixing and enhanced mass transport
[42]. Moreover, ultrasound irradiation activates the reaction mix-
ture by inducing high local temperatures and pressure generated
inside the cavitation bubble and its interfaces when it collapses
and accelerates the reaction rate and shortens the reaction time
[42].
by an external magnet and was washed with acetone, and the recy-
cled catalyst was saved for the next reaction. The recycled catalyst
could be reused five times without any further treatment. No
observation of any appreciable loss in the catalytic activity of nan-
ocatalyst was observed (Fig. 5). As observed in Fig. 6 the XRD of the
recovered nanocatalyst was indexed according to the magnetite
phase (JCPDS card No. 761849), and so there is no considerable
change in its magnetic phase. Thus, the magnetite nanocatalyst is
stable during synthesis of trisubstituted imidazoles under ultra-
sound irradiation.
The possibility of recycling the catalyst was examined using the
reaction of benzil, benzaldehyde, and ammonium acetate under
optimized conditions. Upon completion, the catalyst was separated
In conclusion, have reported an an efficient and environmen-
tally friendly approach for the synthesis of biologically active tri-
substituted imidazoles via condensation of 1,2-diketone with
Scheme 4. Plausible mechanism of the reaction.

746
J. Safari, Z. Zarnegar / Ultrasonics Sonochemistry 20 (2013) 740–746
catalyst, as well as the ability to tolerate a wide variety of substi-
tutions in the reagents.
Acknowledgments
We gratefully acknowledge the financial support from the Re-
search Council of the University of Kashan for supporting this work
by Grant No. (159198/II).
References
[1] A. Kong, P. Wang, H. Zhang, F. Yang, S.P. Huang, Y. Shan, Appl. Catal. A: Gen.
417–418 (2012) 183–189.
[2] J. Zhu, J. He, X. Du, R. Lu, L. Huang, X. Ge, Appl. Surf. Sci. 257 (2011) 9056–9062.
[3] M.Z. Kassaee, H. Masrouri, F. Movahedi, Appl. Catal. A: Gen. 395 (2011) 28–33.
[4] P. Wang, A.G. Kong, W.J. Wang, H.Y. Zhu, Y.K. Shan, Catal. Lett. 135 (2010) 159–
164.
[5] R.A. Sheldon, R.S. Downing, Appl. Catal. A: Gen. 189 (1999) 163–183.
[6] A. Mitsutani, Catal. Today 73 (2002) 57–63.
Fig. 5. Recyclability of SA-MNPs in the reaction of benzil (1 mmol), benzaldehyde
(1 mmol) and ammonium acetate (5 mmol) under ultrasonic waves (35 KHz) at
40 °C.
[7] J. Safari, S.H. Banitaba, S.D. Kalili, J. Mol. Catal. A. Chem. 335 (2011) 46–50.
[8] J.G. Lambardino, E.H. Wiseman, J. Med. Chem. 17 (1974) 1182–1188.
[9] A. Puratchikody, M. Doble, Bioorg. Med. Chem. Lett. 15 (2007) 1083–1090.
[10] J. Safari, S.D. Khalili, M. Rezaei, S.H. Banitaba, F. Monatsh, Chemistry 141
(2010) 1339–1345.
[11] R.B. Sparks, A.P. Combs, Org. Lett. 6 (2004) 2473.
[12] S. Zaman, K. Mitsuru, A.D. Abell, Org. Lett. 7 (2005) 609–611.
[13] J. Tsuji, K. Sakai, H. Nemoto, H. Nagashima, J. Mol. Catal. 18 (1983) 169–176.
[14] D.A. Evans, K.M. Lundy, J. Am. Chem. Soc. 114 (1992) 1495–1496.
[15] B. Radziszewski, Ber Deut Chem. Ges. 15 (1882) 1493–1496.
[16] H.H. Wasserman, Y.O. Long, R. Zhang, J. Parr, Tetrahedron Lett. 43 (2002)
3351–3353.
[17] Y. Kamitori, J. Heterocycl. Chem. 38 (2001) 773–775.
[18] C. Zhang, E.J. Moran, T.F. Woiwade, K.M. Short, A.M.M. Mjalli, Tetrahedron Lett.
37 (1996) 751–754.
[19] I. Lantos, W.Y. Zhang, Y. Shui, D.S. Eggleston, J. Org. Chem. 58 (1993) 7092.
[20] K.H. Bleicher, F. Gerber, Y. Wuthrich, A. Alanine, A. Capretta, Tetrahedron Lett.
43 (2002) 7687–7690.
[21] S. Balalaie, M.M. Hashemi, M. Akhbari, Tetrahedron Lett. 44 (2003) 1709–1711.
[22] D.V. Paone, A.W. Shaw, Tetrahedron Lett. 49 (2008) 6155–6159.
[23] A. Shaabani, A. Rahmati, J. Mol. Catal. A: Chem. 249 (2006) 246–248.
[24] A. Shaabani, A. Rahmati, E. Farhangi, Z. Badri, Catal. Commun. 8 (2007) 1149–
1152.
[25] K.F. Shelke, S.B. Sapkal, S.S. Sonar, B.R. Madje, B.B. Shingate, M.S. Shingare, Bull
Korean Chem. Soc. 30 (2009) 1057–1060.
Fig. 6. XRD patterns of recovered SA-MNPs after five recovery.
[26] S.D. Jadhave, N.D. Kokare, S.D. Jadhave, J. Heterocycl. Chem. 45 (2009) 1461–
1464.
[27] H. Weinmann, M. Harre, K. Koeing, E. Merten, U. Tilestam, Tetrahedron Lett. 43
(2002) 593–595.
various aromatic aldehydes and ammonium acetate using SA-
MNPs as a solid acid catalyst under ultrasound irradiation. Corro-
siveness, safety, less waste, ease of separation and recovery,
replacement of liquid acids with solid acid are all among desirable
factors for the chemical industry which we have considered in our
green chemistry approach. Furthermore, the catalyst could be mag-
[28] J. Liu, J. Chen, J. Zhao, Y. Zhao, L. Li, H. Zhang, Synthesis (2003) 2661–2666.
[29] N.D. Kokare, J.N. Sangshetti, D.B. Shinde, Synthesis (2007) 2829–2834.
[30] M.M. Khodaei, K. Bahrami, I. Kavianinia, J. Chin. Chem. Soc. 54 (2007) 829–833.
[31] J. Safari, S.D. Khalili, S.H. Banitab, H. Dehghani, J. Korean Chem. Soc. 55 (2011)
1–7.
[32] D. Nagargoje, P. Mandhane, S. Shingote, P. Badadhe, C. Gill, Ultrason.
Sonochem. 19 (2012) 94–96.
[33] M.W.I. Schmidt, C. Rumpel, I. Kogel-Knabner, J. Soil Sci. 50 (1999) 87–94.
[34] R. Massart, IEEE Trans. Magn. 17 (1981) 1247–1248.
[35] Y. Deng, Y. Cai, Z. Sun, J. Liu, C. Liu, J. Wei, W. Li, C. Liu, Y. Wang, D. Zhao, J. Am.
Chem. Soc. 132 (2010) 8466–8473.
netically isolated with
a permanent magnet and the yields
achieved above 90% after reused at least 5 times.
[36] Y. Jiang, J. Jiang, Q. Gao, M. Ruan, H. Yu, L. Qi, Nanotechnology 19 (2008) 75714.
[37] B. Hu, J. Pan, H.L. Yu, J.W. Liu, J.H. Xu, Process Biochem. 44 (2009) 1019–1024.
[38] S. Sadjadi, H. Sepehrian, Ultrason. Sonochem. 18 (2011) 480–483.
[39] J. Safari, S.H. Banitaba, Sh. Dehghan Khalili, Ultrason. Sonochem. 19 (2012)
1061–1069.
[40] X. Wang, Y. Wei, J. Wang, W. Guo, C. Wang, Ultrason. Sonochem. 19 (2012) 32–
37.
[41] A. Iskalieva, B.M. Yimmou, P.R. Gogate, M. Horvath, P.G. Horvath, L. Csoka,
Ultrason. Sonochem. 19 (2012) 984–993.
4. Conclusions
An ultrasound assisted, efficient and environmentally friendly
method has been developed for the preparation of 2-aryl-4,5-di-
phenyl imidazoles c in the presence of catalytic amounts of SA-
MNP. This new method offers several advantages including higher
yields, mild reaction conditions, short reaction time, simple work-
up procedure, ease of separation, and recyclability of the magnetic
[42] J. Safari, S.H. Banitaba, S.D. Khalili, Ultrason. Sonochem. 20 (2013) 401–407.