410
S.J. Ahmadi et al. / Ultrasonics Sonochemistry 20 (2013) 408–412
Table 1
metal oxides at the supercritical conditions: (1) at high tempera-
ture dissociation constant (Kw) of water increases, providing more
[OHꢀ] ions for metal cations (Fe3+) to be hydrolyzed to their
hydroxides and through which to the resultant oxides, (2) dielec-
tric constant of water is decreased, and in the same way its solvent
power for dissolution of electrolytes declines. As a consequently, at
elevated temperature supersaturation for precipitation of metal
oxide becomes larger which as a result leads to formation of more
nucleation centers, and therefore formation of smaller particles
(i.e. nanoparticles) (Eqs. (1)–(3)).
Synthesis of 3e under different reaction conditions.
Entry Conditions
Catalyst
Time (min) Yield (%)
1
2
3
4
Stirring
rt
Stirring
rt
Without catalyst
45
11
34
65
97
Fe2O3 nanoparticles 30
Ultrasound-assisted Without catalyst
rt
Ultrasound-assisted Fe2O3 nanoparticles 15
rt
30
Water dissociation : H2O ! Hþ þ OHꢀ
Hydrolysis : Fe3þ þ 2OHꢀ ! FeðOHÞ3
Dehydration : FeðOHÞ3 ! Fe2O3 þ H2O
ð1Þ
ð2Þ
ð3Þ
the reaction time was shortened to 15 min (97% yield). To investi-
gate the role of ultrasonic irradiation in this method, the reactions
were carried out in the presence of the same amount of iron oxide
nanoparticles under stirring condition at room temperature. The
results are summarized in Table 1. It is clear that in the same reac-
tion condition reactions under ultrasonic irradiation led to rela-
tively higher yields and shorter reaction times. Lower yield was
obtained with stirring under the same conditions of time and tem-
perature without catalyst (11%). This optimized reaction condition
was then applied to a number of reactions where the aldehyde was
varied (Table 2). All the reactions proceed to completion at the
time indicated in the Table 2 and the yield data are for the isolated
products. As shown in Table 2, we can see a series of 2 reacted with
1 to give the corresponding products 3 in good yields.
The reaction mechanism is depicted in Scheme 2, which in-
volves a polar transition state starting from a neutral ground state.
Typically, under ultrasonic irradiation ionic reactions are acceler-
ated by physical effects – better mass transport – which is also
called ‘‘False Sonochemistry’’. It was suggested that sonication also
assists in the breakdown of intermediates and desorption of the
products from the surface [16]. The effect of iron oxide nanoparti-
cles can be attributed to the carbonyl complexation by iron cations
leading to electrophilic assistance during nucleophilic attack on
this group [5].
It must be regarded that operational condition for synthesis of
ferric oxide here, extracted from optimization of the synthesis pro-
cess of copper oxide nanoparticles which was our prime goal, and
thus it was discussed in our previous study [13]. Our prior research
had revealed that at supercritical conditions the controlling factors
whose variations significantly influence the characteristic of the
nanoparticles were: ‘‘temperature’’, ‘‘residence time’’, ‘‘initial con-
centration of relevant metal ions’’ and eventually its ‘‘initial pH’’.
The outcomes of that research were specific operational conditions
in which the three target parameters of the study (i.e. purity, yield,
and size of the nanoparticles) attain their optimum values. The sec-
tion started with describing of the procedure of design of experi-
mental array, which was followed by analysis of the responses of
the system using Taguchi–ANOVA analysis. Then, complementary
experiments were discussed that together with the foregoing sta-
tistical methods specify the optimum reaction conditions.
3.2. Reaction mechanism of synthesized azlactones
The use of ultrasound in chemical reactions in solution provides
specific activation based on a physical phenomenon: acoustic cav-
itation. Cavitation is a process in which mechanical activation de-
stroys the attractive forces of molecules in the liquid phase.
Applying ultrasound, compression of the liquid is followed by rar-
efaction (expansion), in which a sudden pressure drop forms small,
oscillating bubbles of gaseous substances. These bubbles expand
with each cycle of the applied ultrasonic energy until they reach
an unstable size; they can then collide and/or violently collapse.
It has been estimated and calculated that the pressure within a
bubble in water can rise to more than one thousand atmospheres,
and the temperature can reach several thousand degrees during a
collapse, as heat conduction cannot keep up with the resulting adi-
abatic heating. As 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 [11].
As part of an ongoing program for the construction of natural
product-like compounds [14,15], we decided to investigate the
possibility of using ultrasonic to accelerate the synthesis of a range
of azlactones. Initial study was performed by treatment of 4-meth-
oxy benzaldehyde and hippuric acid in acetic anhydride at room
temperature under ultrasound irradiation. We observed the forma-
tion of the desired product although the yield was not as good as
expected (65%). Next, we surveyed the efficiency of iron oxide
nanoparticles catalyst for the reaction. The same reaction was car-
ried out in the presence of catalytic amount of iron oxide nanopar-
ticles under ultrasound irradiation at room temperature. The result
was dramatically improved when the reaction was performed in
the presence of catalytic amount of iron oxide nanoparticles and
Finally, the efficacy of the present method for the synthesis of
azlactones was compared with other reported procedures (Table 3)
[5,6,17,18]. We found that the reaction was efficiently promoted
by ultrasound irradiation, and the reaction time was strikingly re-
duced to 10–15 min from hours (1–6 h) required under the tradi-
tional heating conditions in solvent, and the yield was also
increased. In comparison of microwave and ultrasound irradiation
for the above reaction, we observed that this heterocyclic compound
can be prepared under ultrasound irradiation with some improve-
ment in the yield (Table 3).
3.3. Effect of sonication on morphology and size of Fe2O3 nanoparticles
Fig. 4 shows the XRD pattern of both Fe2O3 before and after son-
ication. Obviously, neither related peaks were added nor vanished.
If relative intensity was considered as a morphology criteria in
comparison with reference peaks of haematite iron oxide; then
we can confirm the insistence of morphology during sonification
process. Moreover, calculation of sizes of the particles from their
Table 2
Erlenmeyer–Plöchl reaction with different aldehydes.
Product
X
Time (min)
Yield (%)
Mp (°C) found/reported [15]
3a
3b
3c
3d
3e
H
4-Br
4-NO2
2-NO2
4-OMe
10
10
10
15
15
95
98
98
93
97
168–170/170
204–206/204
240–241/241
164–165/166
164–165/165