A simple, efficient and green procedure for Knoevenagel condensation in water or under solvent-free conditions

Article abstract of DOI:10.1002/jccs.201200391

1,4-Diazabicyclo[2.2.2]octane was used as an efficient catalyst in the Knoevenagel condensation reaction of various kinds of aromatic/aliphatic/ heterocyclic/α,β-unsaturated aldehydes and ketones with active methylene compounds. This is a convenient and rapid method for Knoevenagel condensation, which affords the corresponding substituted electrophilic alkenes in excellent yields. The reaction condition is mild and the method is operationally simple. The products, only E-isomers were detected, did not need to be purified. The use of water as the reaction mediummakes the process environmentally benign. The catalysts can be recycled six times without activity loss.

Full text of DOI:10.1002/jccs.201200391

General Procedure and spectra data
A 5-mL round bottomed flask was charged with the carbonyl compound (1.0 mmol), active methylene
compound (1.0 mmol), catalyst DABCO (12 mg, 10 mol % of the substrates) and water (0.5 mL). The
reaction mixture was stirred at the room temperature. The formation of the products was monitored by
TLC. After completion of the reaction, the reaction mixture often solidified in the round bottomed flask.
The solid mixture was filtered and washed with cold water to remove the catalyst, and then dried to
obtain the products. In general, no further purification method was required. All the products were
previously reported and were characterized by melting point determination and 1HNMR spectroscopy.
The catalyst was recovered by removing the water of the filtrate and reused in the reaction for six times.
In the case of liquid products, GC was used for yield determination. Selected data for typical
compounds are given below.
2-(Phenylmethylene)malononitrile (3a)
White solid, mp. 83-84 ℃. 1H NMR (400 MHz, CDCl3): δ 7.55 (2H, t, J= 8.0 Hz, ArH), 7.64 (1H, t, J= 7.6Hz,
ArH), 7.78 (1H, s, ArH), 7.92 (2H, d, J= 7.6Hz, ArH).
2-(4-Methylphenylmethylene)malononitrile (3b)
White solid, mp. 133-134 ℃. 1H NMR (400 MHz, CDCl3): δ 2.45 (2H, s, CH3), 7.35 (2H, d, J= 8.0 Hz, ArH),
7.22 (1H, s, ArH), 7.82 (2H, d, J= 8.0Hz, ArH).
2-(4-nitrobenzylidene)malononitrile (3c)
1
Yellow solid, mp. 161-162 ℃. H NMR (400 MHz, CDCl3): δ 7.88 (1H, s, =CH), 8.07 (2H, d, J= 8.8 Hz,
ArH), 8.39 (2H, d, J= 8.8Hz, ArH).
2-(4-chlorobenzylidene)malononitrile (3d)
White solid, mp. 164-165 ℃. 1H NMR (400 MHz, CDCl3): δ 7.52 (2H, d, J= 8.4 Hz, ArH), 7.73 (1H, s, =CH),
7.87 (2H, d, J= 8.4Hz, ArH).
2-((naphthalen-4-yl)methylene)malononitrile (3e)
1
White solid, mp. 113-114 ℃. H NMR (400 MHz, CDCl3): δ 7.59-7.70 (3H, m, ArH), 7.96 (2H, d, J= 2.4Hz,
ArH), 8.12 (1H, d, J= 8.0Hz, ArH), 8.27 (2H, d, J= 7.2Hz, ArH), 8.65 (1H, s, =CH).
2-(2-Furylmethylene)malononitrile (3f)
Red solid, mp. 69-70 ℃. 1H NMR (400 MHz, CDCl3): δ 6.73 (1H, dd, J1= 1.6Hz, J2= 3.6Hz, ArH), 7.35 (1H,
d, J= 3.6Hz, ArH), 7.53 (1H, s, =CH), 7.82 (1H, d, J= 1.2Hz, ArH).
2-(Cyclohexylidene)malononitrile (3i)
1
Colourless liquid. H NMR (400 MHz, CDCl3): δ 1.65-1.73 (2H, m), 1.77-1.84 (4H, m), 2.66 (4H, t, J=
6.0Hz).
2-(Butan-2-ylidene)malononitrile (3j)
1
Colourless liquid. H NMR (400 MHz, CDCl3): δ 1.21 (3H, t, J= 7.6Hz, CH2CH3), 2.29 (3H, s, CCH3), 2.62
(2H, q, J= 7.6Hz, CH2CH3).
(E)-ethyl-3-phenyl-2-cyanoacrylate (5a)
White solid, mp. 48-49 ℃. 1H NMR (400 MHz, CDCl3): δ 1.38 (3H, t, J= 7.2Hz, CH3), 4.37 (2H, q, J= 6.8Hz,
CH2), 7.41-7.56 (3H, m, ArH), 7.87-7.94 (2H, m, ArH), 8.21 (1H, s, =CH).
(E)-ethyl 2-cyano-3-p-tolylacrylate (5b)
1
White solid, mp. 90-92 ℃. H NMR (400 MHz, CDCl3): δ 1.39 (3H, t, J= 7.2Hz, CH3), 2.43 (3H, s, CH3)
4.37 (2H, q, J= 6.8Hz, CH2), 7.30(2H, d, J= 8.0Hz, ArH), 7.90 (2H, d= 8.4Hz, ArH), 8.21 (1H, s, =CH).
(E)-ethyl 2-cyano-3-(4-nitrophenyl)acrylate (5c)
1
White solid, mp. 173-174 ℃. H NMR (300 MHz, CDCl3): δ 1.42 (3H, t, J= 7.2Hz, CH3), 4.43 (2H, q, J=
6.9Hz, CH2), 8.14(2H, d, J= 8.7Hz, ArH), 8.31 (1H, s, =CH), 8.36 (2H, d= 9.0Hz, ArH).
(E)-ethyl 3-(4-chlorophenyl)-2-cyanoacrylate (5d)
1
White solid, mp. 89-90 ℃. H NMR (300 MHz, CDCl3): δ 1.40 (3H, t, J= 7.2Hz, CH3), 4.39 (2H, q, J= 7.2

Hz, CH2), 7.48 (2H, d, J= 8.7Hz, ArH), 7.93 (2H, d= 8.7Hz, ArH), 8.20 (1H, s, =CH).
(E)-ethyl 2-cyano-3-(naphthalen-4-yl)acrylate (5e)
1
White solid, mp. 73-74 ℃. H NMR (300 MHz, CDCl3): δ 1.43 (3H, t, J= 6.9Hz, CH3), 4.43 (2H, q, J= 7.2
Hz, CH2), 7.55-7.64 (3H, m, ArH), 7.89-7.95 (1H, m, ArH), 8.00-8.05 (2H, m, ArH), 8.29-8.35 (1H, m, ArH),
9.10 (1H, s, =CH).
(E)-ethyl 2-cyano-5-phenylpenta-2,4-dienoate (5h)
1
White solid, mp. 112-113℃. H NMR (300 MHz, CDCl3): δ 1.37 (3H, t, J= 7.2Hz, CH3), 4.43 (2H, q, J= 6.9
Hz, CH2), 7.26-7.29 (2H, m, ArH), 7.41-7.45 (3H, m, ArH), 8.00-8.05 (2H, m, =CH), 8.02 (1H, dd, J1= 3.9Hz,
J2= 7.2Hz, =CH).