2
N. Azizi et al. / Journal of Molecular Liquids xxx (2013) xxx–xxx
8
8
8
8
2
3
4
5
purchased from Merck. Solvents were distilled before use. All the reac-
tions are monitored by thin layer chromatography (TLC) with UV light
as detecting agent. Melting points were recorded on Buchi 535 melting
point apparatus and are uncorrected.
2.4. Recycling of DES
117
The combination of an atom economic, one-pot, multicomponent 118
reaction and the ease of preparation recovery and reuse of DES as 119
novel reaction media and catalyst are expected to contribute to the 120
development of a novel protocol for the simple and fast preparation 121
of benzopyran and pyran derivatives. The recycling of DES was exam- 122
ined using the reaction of benzaldehyde, malononitrile and dimedone 123
in urea–choline chloride under optimized conditions. After reaction 124
was completed, water (5 mL) was added to the reaction mixture, 125
shacked vigorously and solid was separated by filtration to recover 126
reaction mixture from DES. Finally, DES was recovered by evaporating 127
the water at 80 °C under vacuum and was reused for the next batch 128
and recycled again. The color and FT-IR spectra of recycled DES 129
8
6
2.2. Preparation of deep eutectic solvents (DESs) based choline chloride
8
8
8
9
9
7
8
9
0
1
Deep eutectic solvent based choline chloride was prepared according
to the literature [6], choline chloride and the second component were
mixed on the basis of reported relationships (reported in Table 1), and
heated until a clear liquid appeared. The obtained DES was used without
any further purification (Fig. 1).
9
9
2
3
2.3. General procedure for the synthesis of benzopyran and pyran
derivatives
were similar to the original DES.
130
9
9
9
4
5
6
In the test tube with a magnetic stirrer benzaldehyde (0.5 mmol),
malononitrile (0.5 mmol), dimedone (0.5 mmol), and deep eutectic
solvent (1 mL) were added and the mixture was heated at 80 °C for
60–240 min. After completion of the reaction, water (5 mL) was
added. The DES being soluble in water comes in the water layer.
The solid was separated by filtration and was washed with ethanol–
2
.5. Reaction mechanism
131
The role of the DES as a catalyst is still not clear. Hydrogen bond- 132
Q697
ing and Brønsted basicity of urea are the main factors that influence 133
the reactivity and selectivity of the process. We tentatively propose 134
the mechanism of the present reaction to proceed in a manner similar 135
to that described in the analogous urea catalyzed reactions outlined 136
in Fig. 2. The reversible hydrogen bonding between urea and carbonyl 137
groups giving substrate–solvent complex and activated aldehydes are 138
depicted in Fig. 2. The initial condensation of carbonyl groups with ac- 139
tivated malononitrile with urea in the DES leads to the formation of 140
arylidene malononitrile with the loss of a water molecule. Then nu- 141
cleophilic addition of the enolizable ethylacetoacetate to arylidene 142
malononitrile followed by intramolecular cyclization of the resulting 143
9
9
1
1
1
8
9
00 water. The crude products were obtained in high purity after purifica-
01 tion by recrystallization from ethanol.
02
Selected data:
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
03
04
05
06
07
08
09
10
11
12
13
14
15
16
4i: m.p = 240–242 °C, H NMR (500 MHz, DMSO-d6) δ = 0.95
8
(s, 3H, CH
3
), 1.04 (s, 3H, CH
3
), 2.12 (d, J = 16Hz, 1H, C –H), 2.27
8
6
4
(d, J = 16Hz, 1H, C –H), 2.54 (m, 2H, C –H
2
), 4.20 (s, 1H, C –H),
2
7.06 (s, 2H, NH ), 7.18 (d, J = 8.33Hz, 2H, ArH), 7.36 (d, J =
1
3
8.33Hz, 2H, ArH), C NMR (125 MHz, DMSO-d6): δ 20.1, 26.6,
species produces the 4H-pyran derivatives.
144
27.9, 31.2, 34.3, 49.7, 112.7, 114.0, 114.3, 118.7, 128.3, 139.2,
157.7, 159.0, 161.1, 162.2, 195.0;
4p: m.p = 195–199 °C, 1H NMR (500 MHz, DMSO-d6), δ = 0.95
3. Results and discussion
145
8
(s, 3H, CH
3
), 1.04 (s, 3H, CH
3
), 2.11 (d, J = 16 Hz, 1H, C –H),
As part of our continuing interest in developing the environmen- 146
tal benign synthetic methodologies by using water and deep eutectic 147
solvent as the reaction medium [31–33]. herein, we wish to report 148
the first catalyst-free three component reactions of 1,3-dicarbonyl 149
compound's, aldehydes, and malononitrile to synthesize highly function- 150
alized benzopyran and pyran derivatives in deep eutectic solvents based 151
8
6
2.26 (d, J = 16 Hz, 1H, C –H), 2.51 (m, 2H, C –H
2
), 3.71 (s, 3H,
4
OMe), 4.13 (s, 1H, C –H), 6.85 (d, J = 8.5 Hz, 2H, ArH), 6.94 (s,
2H, NH ), 7.06 (d, J = 8.49 Hz, 2H, ArH); C NMR (125 MHz,
2
13
DMSO-d6): δ 26.8, 28.1, 31.3, 34.2, 49.9, 54.4, 60.2, 113.1, 118.9,
127.8, 135.6, 157.6, 160.9, 195.2.
t1:1
t1:2
Table 1
Optimization of reaction condition in model reaction.
t1:3
t1:4
Entry
Solvent (1 mL)
Temp. [°C]
Yields [%]a
t1:5
1
2
3
4
5
6
7
8
Urea:ChCl (2:1)
Urea:ChCl (2:1)
Urea:ChCl (2:1)
Urea:ChCl (2:1)
Malonic acid:ChCl (1:1)
Citric acid:ChCl (1:1)
Tartaric acid:ChCl (0.5:1)
Glycerine:ChCl (2:1)
25
40
60
80
80
80
80
80
80
80
80
80
80
80
80
50
50
50
95
82
60
68
45
62
55
30
60
50
45
78
t1:6
t1:7
t1:8
t1:9
t1:10
t1:11
t1:12
t1:13
t1:14
t1:15
t1:16
t1:17
t1:18
t1:19
9
LaCl
Water
CH CN
EtOH
MeC
3
:ChCl(2:1)
10
11
12
13
14
15
3
H
6 5
EtOAc
DMF
a
t1:20
Isolated yields ChCl:choline chloride.