General Procedure for Preparation of Chalcones. A mixture of acetophenone (1 mmol, 0.12 g), sodium hydroxide
5 mL, 3N), and ethanol (30 mL, 96%) was stirred at 0ꢃC. 4-Chlorobenzaldehyde (1 mmol, 0.14 g) was added dropwise to the
(
reaction mixture. After 2 h the product was isolated to obtain a yellow oil, which was re-crystallized from absolute ethanol to
afford the pure chalcone. The other derivatives of benzaldehyde were used to prepare various chalcones.
General Procedure for Preparation of Benzylidene Malonates (1a–e). A mixture of diethyl malonate (6.5 mmol,
1
mL) and benzaldehyde (6.5 mmol, 0.69 mL) in 20 mL toluene was stirred at 110ꢃC for 48 h. The reaction mixture was
concentrated in vacuo, and the residual oil was purified by column chromatography to yield the corresponding pure benzylidene
malonates.
General Procedure for Lipase-Catalyzed Aminolysis of Benzylidene Malonate Derivatives (2a–e). In a typical
experiment, benzylidene malonate (1 mmol, 0.25 g) was added to 20 mL toluene. The reaction was initiated by adding 200 mg
of lipase, and the mixture was further stirred at room temperature on an orbital shaker (120 rpm) for 1 h; then 0.2 mL
pyrrolidine was added, and the reaction was monitored by TLC. The mixture was filtered, and the solvent of the filtrate was
evaporated in vacuo. The resulting crude oily product was purified by thin-layer chromatography.
General Procedure for Lipase-Catalyzed Michael Addition of Acetophenone to Chalcone Derivatives (4a–d).
To a mixture of 4-chlorochalcone (0.2 mmol, 0.048 g) in 20 mL toluene, 200 mg of PPL was added. The reaction mixture was
stirred for 1 h. Then 0.2 mL pyrrolidine was added and the mixture stirred for a further 72 h after filtration from solid PPL. The
product was purified by thin-layer chromatography.
1
Diethyl 2-Benzylidenemalonate (1a). H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 7.74 (1H, s), 7.37–7.46 (5H, m),
3
4
7
.33 (2H, q, J = 7.2), 4.30 (2H, q, J = 7.2), 1.33 (3H, t, J = 7.2), 1.28 (3H, t, J = 7.2).
1
Diethyl 2-(3-Chlorobenzylidene)malonate (1b). H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 7.45 (1H, s),
3
.30–7.38 (4H, m), 4.31 (2H, q, J = 7), 4.28 (2H, q, J = 7), 1.30 (3H, t, J = 7), 1.27 (3H, t, J = 7).
1
Diethyl 2-(3-Nitrobenzylidene)malonate (1c). H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 8.31 (1H, s), 7.55–8.24
3
(
4H, m), 4.35 (2H, q, J = 7.2), 4.31, (2H, q, J = 7.2), 1.32 (3H, t, J = 7.2), 1.30 (3H, t, J = 7.2).
1
Diethyl 2-(3-(Dimethylamino)benzylidene)malonate (1d). H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 7.64 (1H,
3
s), 7.38 (2H, d, J = 8.7), 6.65 (2H, d, J = 8.7), 4.38 (2H, q, J = 6.9), 4.28 (2H, q, J = 6.9), 3.04 (6H, s), 1.35 (3H, t, J = 6.9), 1.33
(
3H, t, J = 6.9).
1
Diethyl 2-(3-Methoxybenzylidene)malonate (1e). H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 8.08 (1H, s), 6.88–7.39
3
(
4H, m), 4.30 (2H, q, J = 7.2), 4.27 (2H, q, J = 7.2), 3.85 (3H, s), 1.33 (3H, t, J = 7.2), 1.23 (3H, t, J = 7.2).
–
1
(
Z)-Ethyl 3-Phenyl-2-(pyrrolidine-1-carbonyl)acrylate (2a). Yield 38%. IR (KBr, ꢅ, cm ): 2968, 2872, 1713,
1
1
3
1
634, 1444. H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 7.68 (1H, s), 7.36–7.55 (5H, m), 4.32 (2H, q, J = 6.9), 3.63 (2H, m),
.15 (2H, br.s), 1.78–1.90 (4H, m), 1.34 (3H, t, J = 7.1). C NMR (75 MHz, CDCl , ꢄ, ppm): 165.46, 164.72, 140.20, 133.11,
3
1
3
3
30.46, 129.74, 128.90, 127.04, 61.48, 46.99, 45.51, 25.67, 24.41, 14.29.
–
1
(
Z)-Ethyl 3-(3-Chlorophenyl)-2-(pyrrolidine-1-carbonyl)acrylate (2b). Yield 35%. IR (KBr, ꢅ, cm ): 2975, 2866,
1
1
3
1
713, 1633, 1495, 1450. H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 7.61 (1H, s), 7.33–7.49 (4H, m), 4.31 (2H, q, J = 7.1),
.61 (2H, t, J = 6.5), 3.13 (2H, br.s), 1.78–1.90 (4H, m), 1.33 (3H, t, J = 7.2). C NMR (75 MHz, CDCl , ꢄ, ppm): 165.19,
3
1
3
3
64.50, 138.73, 136.49, 131.62, 130.80, 129.32, 129.22, 61.64, 47.04, 45.57, 25.71, 24.41, 14.29.
–
1
(
Z)-Ethyl 3-(3-Nitrophenyl)-2-(pyrrolidine-1-carbonyl)-acrylate (2c). Yield 30%. IR (KBr, ꢅ, cm ): 2924, 2846,
1
1
713, 1627, 1529, 1441. H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 7.65–8.39 (5H, m), 4.35 (2H, q, J = 7.1), 3.69 (2H, t,
3
1
3
J = 6.6), 3.22 (2H, t, J = 6.3), 1.85–1.97 (4H, m), 1.37 (3H, t, J = 7.2). C NMR (75 MHz, CDCl , ꢄ, ppm): 198.29, 164.48,
3
1
64.00, 148.60, 137.09, 135.30, 134.78, 131.88, 130.06, 124.71, 123.82, 61.97, 47.11, 45.66, 25.79, 24.39, 14.27.
–
1
(
Z)-Ethyl 3-(3-(Dimethylamino)phenyl)-2-(pyrrolidine-1-carbonyl)acrylate (2d). Yield 22%. IR (KBr, ꢅ, cm ):
1
2917, 2846, 1700, 1629, 1591. H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 7.58 (1H, s), 7.41 (2H, d, J = 8.7), 6.62 (2H, d, J = 8.7),
3
4
.27 (2H, m), 3.64 (2H, m), 3.24 (2H, m), 3.02 (6H, s), 1.90 (4H, m), 1.31 (3H, t, J = 7.2).
–
1
(
Z)-Ethyl 3-(3-Methoxyphenyl)-2-(pyrrolidine-1-carbonyl)acrylate (2e). Yield 25%. IR (KBr, ꢅ, cm ): 2968,
1
2
872, 1712, 1633, 1482, 1442. H NMR (300 MHz, CDCl , ꢄ, ppm, J/Hz): 8.02 (1H, s), 6.83–7.52 (4H, m), 4.24 (2H, m), 3.80
3
1
3
(
3H, s), 3.40 (2H, m), 3.05 (2H, br.s), 1.69–1.93 (4H, m), 1.24 (3H, t, J = 7.2). C NMR (75 MHz, CDCl , ꢄ, ppm): 165.78,
3
1
64.88, 157.93, 134.92, 131.67, 128.18, 122.13, 120.65, 110.66, 61.23, 55.53, 46.99, 45.87, 25.98, 25.60, 14.27.
1
(
E)-3-(4-Chlorophenyl)-1-phenylprop-2-en-1-one (3a). Yellow crystals, mp 114–116ꢃC. H NMR (300 MHz, CDCl ,
3
ꢄ, ppm, J/Hz): 8.04 (2H, d, J = 8), 7.78 (1H, d, J = 16), 7.50–7.64 (6H, m), 7.41 (2H, d, J = 8).
1
(
E)-3-(4-Fluorophenyl)-1-phenylprop-2-en-1-one (3b).Yellow crystals, mp 88–90ꢃC. H NMR (300 MHz, CDCl ,
3
ꢄ, ppm, J/Hz): 8.03 (2H, d, J = 8), 7.80 (1H, d, J = 16), 7.46–7.68 (6H, m), 7.13 (2H, t, J = 8.4).
863