J IRAN CHEM SOC
(Scheme 2). The DES has dual roles of catalyst as well as
solvent in this synthesis. To examine the versatility of the
employed DES in this synthesis, simple and substituted
salicylaldehydes (4-hydroxy- and 5-bromo-) with three dif-
ferent active methylene compounds (dimethyl malonate,
ethyl cyano acetate and ethyl 3-oxo-3-phenylpropanoate)
have been used to prepare different coumarin derivatives.
To obtain the best conditions (amount of catalyst, reaction
time and temperature), some preliminary reactions were
done based on the reaction of salicylaldehyde and diethyl
malonate (the model reaction) and the results are listed in
Table 1. Based on the previous reports on the same reac-
tions, 10 mol % of DES in overnight conditions (20 h) was
used to obtain the best reaction temperatures. In the opti-
mization of reaction temperature, according to the obtained
results (entries 1–3 of Table 1), the maximum yield was
obtained at 80 °C.
It should be noticed that the reaction did not pro-
ceed successfully without using DES. To obtain the best
amount of DES, these conditions were used with different
amounts of DES (5, 10, 15 and 20 mol %). These experi-
ments showed that increasing the amount of DES from 5
to 10 mol % extensively increases the reaction yield. How-
ever, by increasing this amount to larger values, any sig-
nificant increasing could not be observed in the reaction
yield (entries 4–7 of the Table 1). Therefore, the reaction
proceeds completely with 10 mol % the DES. To optimize
the reaction time (using optimum values of the other con-
ditions), the time was decreased (from 20 h, entries 9–12
Table 1) and the obvious decreasing in the reaction yield
was observed. Therefore, 20 h has been considered as the
best time for this reaction. The results obtained from these
optimization processes were employed for the synthesis
of the other coumarin derivatives through Knoevenagel
condensation in the presence of choline chloride/zinc
chloride DES (Scheme 2). When our results have been
compared with previous reports related to the synthesis of
coumarins, it will be defined that we avoid using any toxic
catalyst or solvent to ensure that this method could be con-
sidered as a green method. In addition, we have used a sim-
ple procedure (in preparation and separation of product)
and mild condition.
Furthermore, other DESs (choline chloride/SnCl2 and
various molar ratios of choline chloride/ZnCl2) were
employed on the model reaction to examine their effi-
ciencies in this reaction and the results are summarized in
Table 2. It should be mentioned that using another ionic
liquids and basic DES in the synthesis of coumarin deriva-
tives has been previously reported [11, 33–37] and we have
only focused on acidic DESs in this synthesis. When ChCl.
ZnCl2 was employed in the model reaction, the reaction
yield was decreased (to only 25 % after 20 h) and using
ChCl.3ZnCl2, any significant increasing in the reaction
yield has not been observed. In addition, ChCl.2SnCl2 was
also employed as another DES in the model reaction and
the obtained yield for the reaction was only 35 % after
20 h. Therefore, ChCl.2ZnCl2 has been considered as the
best DES for this reaction.
As it shown in the Scheme 2, the reaction yield for dif-
ferent derivatives was between 61 and 96 %. Using simple
salicylaldehyde, the reactions have more yields than sub-
stituted salicylaldehyde and dimethyl malonate has the
maximum yield among all active methylene compounds.
Therefore, the highest yield was observed in the reaction of
salicylaldehyde with dimethyl malonate and the minimum
yield was observed in the reaction of 5-bromo salicylalde-
hyde with ethyl 3-oxo-3-phenylpropanoate. It seems that
the electron donor groups reduce the reactivity of salicylal-
dehyde derivatives.
The role of DES in the mechanistic details of these syn-
theses is depicted in Scheme 3 for the model reaction. This
mechanism has been presented based on the acidic nature
of DES that participates in the reaction as choline cation
and ZnCl3− anion. Zinc chloride acts as Lewis acid and the
chloride ion may be involved in the reaction as Lewis base
to adsorb a proton of diethylmalonate. More details about
the role of DESs in the organic synthesis were defined in
the reported work of Abbot [38].
Table 1 The results of optimization of the reaction parameters for
coumarins synthesis using DES in the model reaction (salicylalde-
hyde and diethyl malonate)
Entry
DES (mol %)
Time (h)
Temp. (°C)
Yield %
1
10
10
10
10
20
15
5
20
20
20
20
20
20
20
20
15
13
4
25
60
80
120
80
80
80
80
80
80
80
80
0
56
96
96
96
96
64
<10
73
30
13
10
2
3
4
5
6
Table 2 The yields of model reaction using different DESs
7
Entry
Catalyst
Yield (%)
8
0
9
10
10
10
10
1
2
3
4
Choline chloride.ZnCl2
Choline chloride.2ZnCl2
Choline chloride.3ZnCl2
Choline chloride.SnCl2
25
96
94
35
10
11
12
2
1 3