J. Chil. Chem. Soc., 57, Nº 4 (2012)
(m, 4H, 2CH2), 4.99 (s, 1H, CH), 5.67 (s br, 1H, NH), 6.90 (t, J = 8.8 Hz, 2H,
Aromatic), 7.22-7.29 (m, 2H, Aromatic).
Also, the reaction was carried out in various solvents. As shown in Table
2, in comparison to conventional methods the yields of the reaction under
solvent-free conditions are higher and the reaction times are shorter.
Diethyl
4-(4-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylate (4c): FT-IR (KBr disc): υ 3358, 2988, 1696, 1652, 1487, 1371,
1299, 1213, 1118, 1093, 1052, 1016 cm-1; 1H NMR (500 MHz, CDCl3, δppm):
1.25 (t, J = 7.0 Hz, 6H, 2CH3), 2.36 (s, 6H, 2CH ), 4.05-4.18 (m, 4H, 2CH2),
4.99 (s, 1H, CH), 5.66 (s br, 1H, NH), 7.19 (d, J =38.3 Hz, 2H, Aromatic), 7.24
(d, J = 8.3 Hz, 2H, Aromatic).
Table 2. Synthesis of diethyl 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-
3,5-dicarboxylate 4a in the presence of [TBA]2[W6O19] (0.04 g) in different
solventsa
Temperature
Diethyl
4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-
Entry
Solvent
Time (min)
Yield (%)b
(°C)
dicarboxylate (4d): FT-IR (KBr disc): υ 3361, 2984, 1694, 1651, 1486, 1370,
1299, 1213, 1118, 1096, 1052, 1013 cm-1; 1H NMR (500 MHz, CDCl3, δppm):
1.25 (t, J = 7.1 Hz, 6H, 2CH3), 2.36 (s, 6H, 2CH ), 4.06-4.17 (m, 4H, 2CH2),
4.97 (s, 1H, CH), 5.62 (s br, 1H, NH), 7.19 (d, J =38.4 Hz, 2H, Aromatic), 7.35
(d, J = 8.4 Hz, 2H, Aromatic).
1
2
3
4
5
MeOH
EtOH
64
90
80
58
55
63
68
60
83
78
PhCH3
110
40
70
Diethyl
2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-
CH2Cl2
100
100
20
dicarboxylate (4e): FT-IR (KBr disc): υ 3345, 2990, 1705, 1645, 1525, 1488,
1371, 1347, 1301, 1213, 1119, 1052, 1022 cm-1; 1H NMR (500 MHz, CDCl3,
δppm): 1.25 (t, J = 7.2 Hz, 6H, 2CH3), 2.40 (s, 6H, 2CH3), 4.05-4.20 (m, 4H,
2CH ), 5.13 (s, 1H, CH), 5.74 (s br, 1H, NH), 7.40 (t, J = 7.9 Hz, 1H, Aromatic),
7.672(dt, J = 7.6, 1.3 Hz, 1H, Aromatic), 8.00-8.05 (m, 1H, Aromatic), 8.16 (t,
J = 2.0 Hz, 1H, Aromatic).
CHCl3
61
6
Solvent-free
80
a
Benzaldehyde (2 mmol), ethyl acetoacetate (4 mmol) and ammonium
acetate (2 mmol).
Diethyl
2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-
b Isolated yields
dicarboxylate (4f): FT-IR (KBr disc): υ 3321, 2979, 1702, 1649, 1518, 1489,
1
1372, 1347, 1302, 1214, 1120, 1095, 1050, 1020 cm-1; H NMR (500 MHz,
The effect of temperature was studied by carrying out the same model
reaction in the presence of 0.04 g of the catalyst and at different temperatures
in solvent-free conditions (Table 3). It was observed that yield is a function
of temperature, so the yield increased as the reaction temperature was raised
and at 80 ºC the product 4a was obtained in high yield. So in other studies all
reactions carried out at 80 ºC in the presence of 0.04 g of [TBA]2[W6O19] under
solvent-free conditions.
CDCl3, δppm): 1.25 (t, J = 7.1 Hz, 6H, 2CH3), 2.39 (s, 6H, 2CH3), 4.07-4.17
(m, 4H, 2CH2), 5.13 (s, 1H, CH), 5.72 (s br, 1H, NH), 7.48 (d, J = 8.7 Hz, 2H,
Aromatic), 8.11 (d, J = 8.7 Hz, 2H, Aromatic).
Diethyl
2,6-dimethyl-4-(4-hydroxyphenyl)-1,4-dihydropyridine-
3,5-dicarboxylate (4g): FT-IR (KBr disc): υ 3435, 3342, 2984, 1689, 1650,
1
1510, 1490, 1372, 1302, 1210, 1121, 1089, 1032 cm-1; H NMR (400 MHz,
DMSO-d , δppm): 1.14 (t, J = 7.2 Hz, 6H, 2CH ), 2.25 (s, 6H, 2CH3), 3.90-4.10
(m, 4H, 26CH ), 4.75 (s, 1H, CH), 6.58 (d, J = 83.4 Hz, 2H, Aromatic), 6.94 (d, J
= 8.4 Hz, 2H2, Aromatic), 8.73 (s, 1H, NH or OH), 9.10 (s br, 1H, NH or OH).
Table 3. Synthesis of diethyl 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-
3,5-dicarboxylate 4a in the presence of [TBA]2[W6O19] (0.04 g) at different
temperatures in solvent-free conditionsa
Diethyl
2,6-dimethyl-4-(4-methylphenyl)-1,4-dihydropyridine-3,5-
dicarboxylate (4h): FT-IR (KBr disc): υ 3360, 3093, 2988, 1698, 1653, 1487,
1369, 1299, 1213, 1118, 1097, 1053, 1019 cm-1; 1H NMR (500 MHz, CDCl3,
δppm): 1.26 (t, J = 7.1 Hz, 6H, 2CH3), 2.31 (s, 3H, CH3), 2.36 (s, 6H, 2CH3),
4.07-4.17 (m, 4H, 2CH ), 4.99 (s, 1H, CH), 5.60 (s br, 1H, NH), 7.04 (d, J = 7.8
Hz, 2H, Aromatic), 7.220 (d, J = 7.8 Hz, 2H, Aromatic).
Entry
Temperature (°C)
Time (min)
Yield (%)b
1
2
3
4
25
50
65
80
90
90
40
30
20
20
25
43
62
83
83
Diethyl 2,6-dimethyl-4-(4-methoxyphenyl)-1,4-dihydropyridine-3,5-
dicarboxylate (4i): FT-IR (KBr disc): υ 3343, 3096, 2984, 1690, 1650, 1509,
1
1491, 1372, 1302, 1254, 1210, 1141, 1122, 1089, 1031 cm-1; H NMR (500
MHz, CDCl , δppm): 1.26 (t, J = 7.1 Hz, 6H, 2CH3), 2.36 (s, 6H, 2CH3), 3.78
(s, 3H, OCH33), 4.07-4.17 (m, 4H, 2CH2), 4.97 (s, 1H, CH), 5.59 (s br, 1H, NH),
6.78 (d, J = 8.7 Hz, 2H, Aromatic), 7.23 (d, J = 8.7 Hz, 2H, Aromatic).
5
a
Benzaldehyde (2 mmol), ethyl acetoacetate (4 mmol) and ammonium
acetate (2 mmol).
RESULTS AND DISCUSSION
b Isolated yields
In order to optimize the reaction conditions, the synthesis of diethyl
2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate 4a was used
as a model reaction. Therefore, a mixture of benzaldehyde (2 mmol), ethyl
acetoacetate (4 mmol), and ammonium acetate (2 mmol) was heated on the oil
bath under various reaction conditions.
To show the generality of this method, the optimized system used for
the synthesis of other 1,4-dihydropyridine derivatives with various aromatic
aldehydes, ethyl acetoacetate and ammonium acetate (Table 4). In all cases
the expected products were obtained in excellent yields in short reaction times.
The efficiency of the reaction is mainly affected by the amount of
[TBA] [W6O19] (Table 1). It showed that no product could be detected in the
absenc2e of this catalyst (entry 1), which indicated that the catalyst should
be absolutely necessary for this condensation reaction. When the amount
of [TBA] [W6O19] was increased, a ramp in the yield of the product 4a was
observed.2The optimal amount of [TBA]2[W O19] was 0.04 g (entry 5), the
higher amount of the catalyst did not increase6the yield (entry 6).
Table 1. Effect of the amounts of [TBA]2[W6O19] on the model reactiona
Entry
Catalyst (g)
None
0.01
Time (min)
Yield (%)b
1
2
180
90
60
40
20
20
0
55
67
74
83
83
3
0.02
4
0.03
5
0.04
6
0.05
a
Benzaldehyde (2 mmol), ethyl acetoacetate (4 mmol) and ammonium
acetate (2 mmol) at 80°C.
b Isolated yields
1433