L. Edjlali, R. H. Khanamiri
Scheme 1
Table 1 Effects of catalyst amount, solvent, and temperature on the
reaction yield
Entry
Catalyst amount/g
Solvent
Temp./°C
Yield/%a
1
2
0.04
0.04
0.04
0.04
0.02
0.03
0.05
0.04
0.04
–
PhCH3
MeOH
EtOH
H2O
50
50
50
50
50
50
50
40
25
50
69
95
94
91
41
80
92
67
28
48
3
4
5
H2O
6
H2O
7
H2O
8
H2O
bronchiodilator, hepatoprotective, cardiotonic, and anti-al-
lergic activities [13–15]. In addition, some of them have
been used as the antimalarial, antifungal, analgesics, and
herbicidal agents [16, 17]. Thus, development of new
greener approaches for their synthesis is still of interest
[18–21].
9
H2O
10
H2O
Reaction conditions: benzaldehyde (1a, 1.00 mmol), malononitrile (2,
1.00 mmol), dimedone (3a, 1 mmol), 5 cm3 solvent, 9 h
a
Isolated yield
After our efforts for development of new routes for the
synthesis of heterocyclic compound [22, 23], herein a
green route was developed for the synthesis of pyrans 4 in
the presence of TiO2 NPs as the heterogeneous recyclable
catalyst, in H2O at 50 °C within 9 h (Scheme 1).
washed with acetone (3 9 5 cm3), dried in the oven
(100 °C, 5 h), and was used again. This procedure was
carried out for six times. Results of these successive
reactions are shown in the Table 3. It is clear that by
successive use of the catalyst, no decrease in the reactivity
can be seen for TiO2 NPs. Also, the image of the catalyst
before and after the reaction is shown in Fig. 2 which
indicate any changes in catalyst.
Results and discussion
Synthesis of pyrans 4 was investigated via three-compo-
nent reaction of an aldehyde 1, malononitrile (2), and a
cyclic CH-acid 3 in the presence of TiO2 NPs. For opti-
mization of the reaction conditions, the reaction of
benzaldehyde (1a), malononitrile (2), and dimedone (3a)
was investigated as a model reaction (Table 1). As shown
in the Table 1, it was found that 0.04 g of TiO2 NPs in H2O
at 50 °C is the best reaction conditions (entry 3). The
reaction gave high yields in MeOH or EtOH as the solvent,
but H2O was selected due to correspondence with green
chemistry principles. Also, the reaction in the absence of
TiO2 NPs gave the corresponding product in 48 % yield
(entry 10).
The represented approach has some advantages such as
green reaction conditions such as heterogeneous catalyst,
and water as the solvent. The catalyst is cheap, available,
and non-toxic. The reaction is economical regarding
recycling of TiO2 NPs.
The results of our catalyst are compared with previous
reports were performed with mesoporous silica nanoparti-
cles [18], clinoptilolite zeolite [19], amino-functionalized
silicagel [20], and choline hydroxide [21] as the catalysts
with respect to their yields, solvents, and temperatures
required for the reaction. As shown in Table 4, in the case
of TiO2 NPs the reaction yield is comparable with pervious
work in milder reaction conditions.
To evaluate the use of this interesting approach, a
variety of aldehydes and cyclic CH-acids were examined of
which good library of pyrans 4 was obtained. The struc-
tures of products are shown in Fig. 1. Diverse structural
pyrans were obtained in high yields using various aldehy-
des and CH-acids. For aliphatic aldehydes, the reaction was
performed with dimedone as the CH-acid in low yields and
other CH-acids did not carry out the reaction. These
compounds were characterized unambiguously using
melting point and NMR data (Table 2).
Although no detailed mechanistic studies have been
carried out at this point, it is conceivable that the initial
event is the activation of aldehyde 1 via coordination
with TiO2. After that, the activated aldehyde 1 under
nucleophilic attack of malononitrile (2) produces inter-
mediate 5. Another nucleophilic attack from CH-acid to
intermediate 5 led to the formation of intermediate 6
which via intramolecular cyclization afforded products 4
(Scheme 2).
TiO2 NPs could be recovered and reused in this reaction
for several times. For examination of the recyclability of
TiO2 NPs, recovered TiO2 NPs from the reaction between
benzaldehyde (1a), malononitrile (2), and dimedone (3a),
In conclusion, TiO2 NPs were found as a recyclable
heterogeneous catalyst for the synthesis of pyran’s annu-
lated heterocyclic systems in H2O as the green solvent. The
present route has the advantages such as good yields, green
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