Knoevenagel condensation of aldehydes with active methylene compounds catalyzed by MgC2O4/SiO2 under microwave irradiation and solvent-free conditions

Article abstract of DOI:10.1007/s11164-011-0355-2

MgC₂O₄/SiO₂ catalyzes the efficient Knoevenagel condensation of aldehydes with active methylene compounds in solvent-free conditions under microwave irradiation to give alkenes derivatives in excellent yields. MgC₂

Full text of DOI:10.1007/s11164-011-0355-2

Res Chem Intermed (2012) 38:393–402
DOI 10.1007/s11164-011-0355-2
Knoevenagel condensation of aldehydes with active
methylene compounds catalyzed by MgC O /SiO
2
4
2
under microwave irradiation and solvent-free
conditions
Shizhen Yuan
•
Zhen Li Ling Xu
•
Received: 31 May 2011 / Accepted: 26 July 2011 / Published online: 20 August 2011
Ó Springer Science+Business Media B.V. 2011
Abstract MgC O /SiO catalyzes the efficient Knoevenagel condensation of
2
4
2
aldehydes with active methylene compounds in solvent-free conditions under
microwave irradiation to give alkenes derivatives in excellent yields. MgC O /SiO
2
2
4
can be reusable for Knoevenagel condensation. However, ketones have been found
to be unsatisfactory in the reaction under the same conditions.
Keywords Knoevenagel condensation Á Solvent-free conditions Á
Microwave irradiation Á Magnesium oxalate
Introduction
The Knoevenagel condensation reaction is one of the most important methods for
the formation of carbon–carbon bonds [1], which the alkenes are obtained from
carbonyl compounds and active methylene compounds in the presence of a basic
catalyst or Lewis acid catalyst. Traditionally, the Knoevenagel condensation
reaction is carried out in organic solvents (e.g., benzene, ethanol, and DMF) by
using organic bases as catalysts, such as aliphatic amines, urea, ethylenediamine,
and piperidine or their corresponding ammonium salts [1], and the amino acids
glycine or b-alanine [2]. Due to economical and environmental concerns, recently,
the use of inorganic solids as catalysts for the Knoevenagel reaction is increasing
rapidly, these catalysts including ZnCl [3], CdI [4], TiCl [5], Al O [6], Ni-SiO
2
2
2
4
2
3
[
KF or NP/NaNO ] [11] and synthetic phosphate (Na CaP O [12], Ca P O [12]
7], MgO or ZnO [8], AlPO –Al O [9], KF-Al O [10], natural phosphate [(NP)/
4 2 3 2 3
3
2
2
7
2 2 7
and K NiP O [13]), zeolite [14], alkylamine-functionalized silica gel [15], resins
2
2 7
[
16], LDH-F hydrotalcite [17], MCM-41 [18], and modified Mg–Al hydrotalcite,
S. Yuan (&) Á Z. Li Á L. Xu
Department of Chemistry, Anhui University of Architecture, Hefei 230022, China
e-mail: yuanshzh3@hotmail.com
123

394
S. Yuan et al.
etc. [19]. Ionic liquid [20], microwave-assisted reactions and solvent-free reaction
have also been reported [21].
These reactions often involve milder reaction conditions, easier work-up, and
higher selectivity than similar homogenous reactions. Nevertheless, most of these
known methods suffered from significant limitations, which include toxic reagents,
harsh reaction conditions, low yields, or long reaction times. Therefore, it is
necessary to develop a simple, efficient and more general method for the
Knoevenagel condensation.
Herein, we describe a rapid and simple procedure for the Knoevenagel
condensation reaction. Various aldehydes smoothly react with active methylene
compounds (malononitrile or ethyl cyanoacetate) by using MgC O /SiO as a
2
4
2
catalyst under solvent-free and microwave-irradiation conditions (Scheme 1).
Results and discussion
Our initial study was started by reacting benzaldehyde (0.01 mol) with malono-
nitrile (0.01 mol) or ethyl cyanoacetate (0.01 mol) under different conditions.
The results are summarized in Table 1.
As shown in Table 1, 3a (2-nitrile-3-phenyl-acrylonitrile) and 3g (2-nitrile-
-phenyl-ethyl-acrylate) were not observed in the absence of the catalyst under
3
solvent-free and MW activation (entries 1, 4, 14, Table 1). The catalytic activity of
magnesium oxalate was better than that of calcium oxalate (entries 2, 3, Table 1).
When MgC O was used alone, a sticky mixture was formed and the yield was low.
2
4
For overcoming this limitation, we used a small amount of SiO together with
2
MgC O , where the silicon dioxide acts as water-absorbing agents, anti-caking
2
4
agent, and dispersant. Surprisingly, we found that 3a was obtained in higher yields
entries 5, 6, Table 1). Augment of the catalyst moderately helped to increase yields
(
of Knoevenagel condensation (entries 7, 8, Table 1). It is necessary to control for
the appropriate irradiation time to increase the yield of product 3 under certain
power (entries 8–12, 14, 15, Table 1). In similar experimental conditions with the
same amount of starting materials and catalyst, conventional heating needed 80 min
to give the expected product in similar yield (entry 13, Table 1). Inspiringly,
catalyst MgC O /SiO can be used in circulation after simple treatment. A recycling
2
4
2
experiment exhibited that the activity of the catalyst decreased with the increase
R
H
CN
R
H
CN
R1
MgC O / SiO
2
2
4
O
+
MW
R1
1
2
3
Scheme 1 Knoevenagel condensation of aldehydes 1 and active methylene compounds 2 catalyzed by
MgC /SiO
2
O
4
2
1
23

Knoevenagel condensation of aldehydes with active methylene
395
Table 1 Knoevenagel condensation of benzaldehydes with ethyl cyanoacetate and malononitrile cata-
lyzed by magnesium oxalate or calcium oxalate under solvent-free and microwave irradiation
a,b
Time (min) Power (W) Yield (%)
Entry
R
R
1
Catalyst
1
2
3
4
5
6
7
8
9
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CO
CO
CN
CN
CN
CN
CN
CN
/
1
400
400
400
400
400
400
400
400
400
400
460
320
/
/
0.05 g CaC
2
O
4
1
3a (63)
3a (67)
/
0.05 g MgC
0.05 g SiO
0.05 g CaC
2
O
4
1
2
1
2
O
4
/0.01 g SiO
2
1
3a (82)
3a (87)
3a (89)
3a (91)
3a (93)
3a (86)
3a (89)
3a (84)
3a (85)
/
0.05 g MgC
0.10 g MgC
0.10 g MgC
0.10 g MgC
0.10 g MgC
0.10 g MgC
0.10 g MgC
0.10 g MgC
/
2
O
4
4
4
4
4
4
4
4
/0.01 g SiO
/0.01 g SiO
/0.02 g SiO
/0.02 g SiO
/0.02 g SiO
/0.02 g SiO
/0.02 g SiO
/0.02 g SiO
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
O
O
O
O
O
O
O
1
1
1.2
1.5
1.2
1.2
10
11
12
13
14
15
16
17
18
19
20
21
a
c
90
2
2
C
C
2
H
H
5
5
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
400
400
400
400
400
400
400
400
2
0.1 g MgC
2
O
4
/0.02 g SiO
2
3g (87)
3a (91)
3a (89)
3a (88)
3a (85)
3a (77)
3a (69)
d
0.12 g 1st recovery cat.
0.12 g 2nd recovery cat.
0.12 g 3rd recovery cat.
0.12 g 4th recovery cat.
0.12 g 5th recovery cat.
0.12 g 6th recovery cat.
The isolated yields are reported
1 13
The pure product was identified by IR, H, C NMR, and HRMS
b
c
The reaction temperature was at 80 °C
Using recovery catalyst: refer to experiment
d
of recycling times; after being used for six times, the reaction yields declined from
1 to 69% (entries 16–21, Table 1). Therefore, the effective number of catalyst
reuses is no less than four times from Table 1.
9
After a comprehensive survey of the reaction conditions, MgC O /SiO was
2
4
2
considered as an appropriate catalyst for the Knoevenagel condensation reaction.
Subsequently, a variety of carbonyl compounds were examined by using this
method (Scheme 1); the mixture of aldehyde 1 (0.01 mol), active methylene
compounds 2 (0.01 mol), and MgC O /SiO (0.12 g) was subjected to microwave
2
4
2
irradiation at 400 W intermittently at 1.2 min. The results are shown in Table 2.
Benzaldehyde and its derivatives could smoothly implement Knoevenagel
condensation reaction with active methylene compounds 2 to afford the corre-
sponding substituted alkene products 3 in excellent yields under solvent-free and
MW activation conditions (entries 1–5, 7–14, Table 2). The electronic effect of the
substitution group seldom had an effect on reaction yields (entries 2–5, 8–14,
Table 2). While using ethyl cyanoacetate as an active methylene compound 2, it is
123

396
S. Yuan et al.
Table 2 Microwave promoted Knoevenagel condensation of aldehydes with active methylene com-
O
pounds in the presence of MgC
2
4
/SiO
2
under solvent-free conditions
a,b
Entry
Substrate 1
R
1
Time
min)
Yield
(%)
M.p./°C or
b.p./°C (Pa)
References
(
1
2
3
4
5
6
CN
CN
CN
CN
CN
CN
1.2
1.2
1.2
1.0
1.0
1.2
3a (93)
3b (96)
3c (95)
3d (91)
3e (93)
3f (81)
81–82
130–132
114–116
162–164
161–162
72–74
[22]
CHO
[22]
H3C
H3CO
Cl
CHO
[22]
CHO
CHO
CHO
[22]
[22]
O2N
[12, 24]
CHO
O
7
CO
2
C
2
H
5
1.2
3g (87)
49–50
[22]
CHO
8
9
CO
CO
CO
CO
2
2
2
2
C
2
C
2
C
2
C
2
H
5
H
5
H
5
H
5
1.2
1.2
1.2
1.2
3h (93)
3i (97)
3j (86)
3k (88)
93–94
87–89
[22]
H3C
H3CO
HO
CHO
[22]
CHO
1
0
1
170–171
95–96
[22], [23]
[22]
CHO
1
O
O
CHO
c
1
2
CO
2
2
C
2
2
H
5
5
1.2
0.8
3m (90)
3n (95)
125–127
92–93
[25]
[22]
(
H3C)2N
Cl
CHO
1
3
CO
C
H
CHO
1
1
4
5
CO
2
2
C
2
2
H
5
5
0.8
1.2
3p (92)
3q (85)
171–172
92–93
[22]
O2N
CHO
CO
C
H
[12, 24]
CHO
O
16
17
18
CH
3
(CH
2
)
4
CHO
CN
CN
CN
1.2
1.2
1.2
3r (79)
3s (71)
3t (/)
Liquid
Liquid
/
[24]
[24]
/
OCH(CH
2
)
3
CHO
O
C H 3
a
The isolated yields are reported
1 13
The pure product was identified by IR, H, C NMR and HRMS
b
1
23

Knoevenagel condensation of aldehydes with active methylene
397
worthy to note that the stereochemistry of all product 3 obtained were E-isomers
exclusively [24b, 24c]. Heterocycle aromatic aldehyde, such as Furfural, also
underwent the above reaction to produce the product 3 in high yields (entries 6, 15,
Table 2). Usually, aliphatic aldehydes gave lower yields of alkene products 3,
however aliphatic aldehydes showed good yield in 79% under such reaction
condition (entry 16, Table 2). When pentanedial was used in the present reaction,
the product [1,1,7,7-tetracyano-1,6-heptadiene] was formed with two units of
olefinic bond (entries 17, Table 2). However, unlike aldehydes, ketones provided
none of the desired Knoevenagel alkenes (entries 18, Table 2).
Based on our experimental results and previous reports [12], a plausible catalytic
2
mechanism of MgC O could be ascribed to the Mg –O acid–base pair that
?
2-
2
2
participates in the catalysis of deprotonation, aldol, and dehydration steps, as
proposed in Scheme 2.
In conclusion, MgC O /SiO has been employed as an appropriate catalyst for
2
4
2
the Knoevenagel condensation reaction considering its (a) high efficiency, (b) easy
R
N C
R
2
N C
R 2
O
deprotonation
R
1
H
O
H
O
O
O
O
O
M g
M g
O
O
A ldol
H
H
O
R
2
R
2
H
H
O
O
O
O
O
N C
N C
O
R
O
R
O
O
R
1
R
1
M g
M g
O
O
O
dehyd ration
M g
O
R
C N
2 2
S iO ·H O
R
1
R
2
Scheme 2 Mechanism of Knoevenagel condensation catalyzed by MgC
2
O
4
/SiO
2
123

398
S. Yuan et al.
availability, (c) low cost, (d) operational simplicity, and (e) recycling. This catalyst
is significantly effective for the present reaction to form alkene products in excellent
yields under solvent-free and MW irradiation reaction conditions.
Experimental
All melting points were determined on a WT-melting point apparatus. IR (Perkin-
1
13
Elmer, 2000 FTIR), H NMR, and C NMR were recorded on a Bruker AC-300 FT
spectrometer using TMS as the internal standard. The chemical shifts (d) and
coupling constants (J) were expressed in ppm and Hz, respectively. HRMS was
recorded on an MS-GC (HP5890 (II)/HP 5972, EI) spectrometer. TLC was
purchased from Anhui Liangchen Silicon Material Co., Ltd. and all material from
Aldrich and used directly as received. The reactions were carried out in a multimode
microwave oven (frequency: 2,450 Hz; maximal power: 1,600 W).
General procedure for the synthesis of Knoevenagel alkenes
Mixture of carbonyl compounds 1 (0.01 mol), active methylene compounds 2
0.01 mol) and MgC O /SiO (0.12 g, 0.10/0.02 g) was subjected to microwave
2 4 2
(
irradiation at 400 W intermittently for a specified time (Table 2). After completion
of the reaction as indicated by TLC, the reaction mixture was cooled to room
temperature and extracted with CH Cl , and filtered. The catalyst filtered was then
2
2
dried at 80 °C for 2 h and used in circulation. The organic phase is washed with
saturated brine, dried over anhydrous magnesium sulfate, and concentrated in
vacuo. The pure products were obtained by flash chromatography on silica gel
1
13
eluting with petroleum ether/EtOAc (1:6, V:V), and identified by IR, H, C NMR,
and HRMS. All compounds obtained were consistent with authentic ones in the
literature [12, 22, 24, 25].
2
-(Phenylmethylene)-malononitrile (3a)
-
1 1
Solid, m. p. 81–82 °C; IR: 3,032, 2,223, 1,590, 1,218, 755 cm ; H NMR (CDCl ,
3
3
00 MHz) d: 7.55–7.58 (m, 3H, Ph), 7.73 (s, 1H, = CH), 7.91 (d, J = 7.8 Hz, 2H,
13
Ph); C NMR (CDCl , 75 MHz) d: 163.1, 134.6, 128.9, 127.7, 126.4, 115.2, 114.3,
3
8
0.3; HRMS: calcd for C H N : 154.3572, found: 154.3685.
10 6 2
2
-(4-Methylphenylmethylene)-malononitrile (3b)
-
1
1
Solid, m. p. 131–132 °C; IR: 3,033, 2,223, 1,589, 1,220, 841 cm ; H NMR
CDCl , 300 MHz) d: 7.84 (d, 2H, J = 8.2 Hz, Ph), 7.72(s, 1H, = CH), 7.34(d, 2H,
(
3
1
3
J = 8.2 Hz, Ph), 2.47 (s, 3H, CH3); C NMR (CDCl , 75 MHz) d: 164.3, 134.9,
3
132.3, 129.7, 126.4, 114.7, 114.3, 81.1, 21.2; HRMS: calcd for C H N : 168.2394,
11 8 2
found: 168.2536.
1
23

Knoevenagel condensation of aldehydes with active methylene
399
2
-(4-Methyoxyphenylmethylene)-malononitrile (3c)
-
1
1
Solid, m. p. 114–116 °C; IR: 3,031, 2,224, 1,587, 1,279, 838 cm ; H NMR
(
CDCl , 300 MHz) d: 7.86 (d, 2H, J = 8.2 Hz, Ph), 7.74(s, 1H, = CH), 7.28 (d,
3
13
2
1
1
H, J = 8.2 Hz, Ph), 3.74 (s, 3H, OCH3); C NMR (CDCl , 75 MHz) d: 164.1,
3
58.7, 131.3, 129,5, 121.6, 114.7, 114.3, 81.4, 67.1; HRMS: calcd for C H N O:
84.4318, found: 184.3625.
1
1 8 2
2
-(4-Chlorophenylmethylene)-malononitrile (3d)
-
1
1
Solid, m. p. 162–164 °C; IR: 3,032, 2,228, 1,587, 1,273, 827 cm ; H NMR
(
CDCl , 300 MHz) d: 7.86 (d, 2H, J = 8.5 Hz, Ph), 7.72 (s, 1H, = CH), 7.38 (d,
3
13
2
H, J = 8.2 Hz, Ph); C NMR (CDCl , 75 MHz) d: 164.2, 134.3, 133.8, 128,3,
3
1
27.6, 114.7, 114.3, 81.1; HRMS: calcd for C H N Cl: 188.8717, found: 188.8695.
1
0 5 2
2
-(4-Nitrophenylmethylene)-malononitrile (3e)
-
1
1
Solid, m. p. 161–162 °C; IR: 3,033, 2,232, 1,587, 1,273, 831 cm ; H NMR
CDCl , 300 MHz) d: 8.2(s, 1H, = CH), 7.9 (d, 2H, J = 8.5 Hz, Ph), 7.56 (d, 2H,
(
3
1
3
J = 8.5 Hz, Ph); C NMR (CDCl , 75 MHz) d: 164.0, 147.3, 140.2, 127,4, 124.6,
3
1
15.0, 114.8, 81.6; HRMS: calcd for C H N O : 199.1877, found: 199.1693.
10 5 3 2
2
-(2-Furylmethylene)-malononitrile (3f)
-
1 1
Solid, m. p. 69–71 °C; IR: 3,045, 2,225, 1,596, 1,298, 822, 761 cm ; H NMR
(
CDCl , 300 MHz) d: 7.81 (s, 1H, = CH), 7.42 (d, 1H, J = 4.2 Hz, furyl), 7.31 (d,
3
13
1
1
1
H, J = 4.2 Hz, furyl), 6.72–6.75 (m, 1H, furyl); C NMR (CDCl , 75 MHz) d:
3
64.0, 156.2, 143.2, 116.1, 115.8, 112.3, 109.8, 87.5; HRMS: calcd for C H N O:
44.2174, found: 144.2169.
8
4 2
Ethyl (E)-2-cyano-3-phenyl-2-acrylate (3g)
Solid, m. p. 49–50 °C; IR: 3,034, 2,213, 1,720, 1,674, 1,583, 861 cm ; H NMR
-
1 1
(
CDCl , 300 MHz) d: 8.21 (s, 1H, = CH), 7.92 (d, J = 8.2 Hz, 2H, Ph), 7.42–7.57
3
13
(
m, 3H), 4.21 (q, J = 7.2 Hz, 2H, OCH ), 1.35 (t, J = 7.2 Hz, 3H, CH CH );
3
C
2
2
NMR (CDCl , 75 MHz) d: 164.1, 153.4, 134.2, 128.1, 127.5, 126.1, 115.2, 106.3,
3
5
6.3, 17.3; HRMS: calcd for C H NO : 201.5201, found: 201.5317.
12 11 2
Ethyl (E)-2-cyano-3-(4-methylphenyl)-2-acrylate (3h)
-
1 1
Solid, m. p. 93–94 °C; IR: 3,032, 2,214, 1,713, 1,670, 1,579, 812 cm ; H NMR
CDCl , 300 MHz) d: 8.23 (s, 1H, = CH), 7.83 (d, 2H, J = 8.2 Hz, Ph), 7.31 (d,
(
3
2
H, J = 8.2 Hz, Ph), 4.22 (q, J = 7.2 Hz, 2H, OCH ), 2.43 (s, 3H, CH ), 1.37 (t,
2 3
1
3
J = 7.2 Hz, 3H, CH CH ); C NMR (CDCl , 75 MHz) d: 164.2, 157.1, 134.2,
2
3
3
1
28.6, 127.8, 126.3, 114.9, 106.2, 57.2, 21.2, 17.1; HRMS: calcd for C H NO :
13 13 2
2
15.4319, found: 215.4591.
123

400
S. Yuan et al.
Ethyl (E)-2-cyano-3-(4-Methoxyphenyl)-2-acrylate (3i)
-
1 1
Solid, m. p. 87–89 °C; IR: 3,035, 2,213, 1,728, 1,653, 1,564, 832 cm ; H NMR
CDCl , 300 MHz) d: 8.20 (s, 1H, = CH), 7.78 (d, 2H, J = 8.2 Hz, Ph), 7.21 (d,
(
3
2
H, J = 8.2 Hz, Ph), 4.23 (q, J = 7.2 Hz, 2H, OCH ), 3.73 (s, 3H, OCH3), 1.35 (t,
2
1
3
J = 7.2 Hz, 3H, CH CH ); C NMR (CDCl , 75 MHz) d: 164.4, 160.8, 157.3,
2
3
3
1
28.2, 127.5, 115.2, 106.9, 102.1, 57.2, 54.7, 17.3; HRMS: calcd for C H NO :
13 13 3
2
31.3185, found: 231.3217.
Ethyl (E)-2-cyano-3-(4-hydroxyphenyl)-2-acrylate (3j)
-
1 1
Solid, m. p. 170–171 °C; IR: 3,271, 3,033, 2,231, 1,716, 1,663, 1,571, 831 cm ; H
NMR (CDCl , 300 MHz) d: 8.21 (s, 1H, = CH), 7.85 (d, 2H, J = 8.2 Hz, Ph), 7.23
3
(
d, 2H, J = 8.2 Hz, Ph), 6.21–6.53 (br, 1H, OH), 4.21 (q, J = 7.2 Hz, 2H, OCH ),
2
1
3
1
1
2
.36 (t, J = 7.2 Hz, 3H, CH CH ); C NMR (CDCl , 75 MHz) d: 164.1, 157.6,
3
2
3
34.2, 128.1, 127.5, 115.7, 113.6, 107.4, 57.1, 17.8; HRMS: calcd for C H NO :
11
1
2
3
17.4317, found: 217.4293.
Ethyl (E)-2-cyano-3-piperonyl-2-acrylate (3k)
-
1 1
Solid, m. p. 95–96 °C; IR: 3,271, 3,033, 2,223, 1,727, 1,591, 758 cm ; H NMR
CDCl , 300 MHz) d: 8.19 (s, 1H, = CH), 7.32 (d, 1H, J = 8.0 Hz, Ph), 7.11 (d,
(
3
1
J = 7.2 Hz, 2H, OCH ), 1.35 (t, J = 7.2 Hz, 3H, CH CH ); C NMR (CDCl3,
H, J = 8.0 Hz, Ph), 6.27 (d, 1H, J = 8.0 Hz, Ph), 6.03 (s, 2H, OCH O), 4.25 (q,
2
1
3
2
2
3
7
5 MHz) d: 165.2, 157.8, 147.3, 146.1, 128.6, 120.3, 118.6, 115.2, 112.1, 107.4,
9
2.6, 57.1, 17.8; HRMS: calcd for C H NO : 245.2136, found: 245.2561.
1
3
11
4
Ethyl (E)-2-cyano-3-(4-N,N-dimethylphenyl)-2-acrylate (3m)
-
1 1
Solid, m. p. 125–127 °C; IR: 3,033, 2,224, 1,735, 1,673, 1,583, 815 cm ; H NMR
CDCl , 300 MHz) d: 8.21 (s, 1H, = CH), 7.85 (d, 2H, J = 8.2 Hz, Ph), 7.23 (d,
(
3
2
H, J = 8.2 Hz, Ph), 4.22 (q, J = 7.2 Hz, 2H, OCH ), 3.15 (s, 6H, N(CH ) ), 1.37
2 3 2
1
3
(
t, J = 7.2 Hz, 3H, CH CH ); C NMR (CDCl , 75 MHz) d: 164.1, 157.6, 143.2,
3
2
3
1
28.3, 127.1, 115.9, 114.2, 106.2, 57.2, 43.2, 17.6; HRMS: calcd for C H N O :
4 16 2 2
1
2
44.3707, found: 244.3695.
Ethyl (E)-2-cyano-3-(4-chlorophenyl)-2-acrylate (3n)
-
1
1
Solid, m. p. 92–93 °C; IR: 3,034, 2,224, 1,726, 1,673, 1,591, 819 cm ; H NMR
CDCl , 300 MHz) d: 8.25 (s, 1H, = CH), 7.87 (d, 2H, J = 8.2 Hz, Ph), 7.63 (d,
(
3
2
H, J = 8.2 Hz, Ph), 4.23 (q, J = 7.2 Hz, 2H, OCH ), 1.36 (t, J = 7.2 Hz, 3H,
1
2
3
CH CH ); C NMR (CDCl , 75 MHz) d: 165.7, 158.2, 134.7, 133.6, 128.9, 127.4,
2
3
3
1
18.1, 106.2, 57.2, 17.3; HRMS: calcd for C H NO Cl: 235.5707, found:
12 10 2
2
35.5695.
1
23

Knoevenagel condensation of aldehydes with active methylene
401
Ethyl (E)-2-cyano-3-(4-nitropheny1)-2-acrylate (3p)
-
1 1
Solid, m. p. 168–170 °C; IR: 3,031, 2,225, 1,723, 1,673, 1,582, 812 cm ; H NMR
CDCl , 300 MHz) d: 8.35 (s, 1H, = CH), 8.17 (d, 2H, J = 8.6 Hz, Ph), 7.87 (d,
(
3
2
H, J = 8.6 Hz, Ph), 4.25 (q, J = 7.2 Hz, 2H, OCH ), 1.35 (t, J = 7.2 Hz, 3H,
2
1
3
CH CH ); C NMR (CDCl , 75 MHz) d: 165.1, 157.3, 148.1, 142.6, 127.9, 124.2,
2
3
3
1
16.8, 107.1, 58.6, 17.8; HRMS: calcd for C H N O : 246.5214, found: 246.5195.
12 10 2 4
Ethyl (E)-2-cyano-3-(2-fury1)-2-acrylate (3q)
-
1 1
Solid, m. p. 92–93 °C; IR: 3,037, 2,215, 1,754, 1,671, 1,534, 872 cm ; H NMR
CDCl , 300 MHz) d: 8.01 (s, 1H, = CH), 7.72 (d, 1H, J = 4.2 Hz, furyl), 7.36 (d,
(
3
1
1
1
1
H, J = 4.2 Hz, furyl), 6.62–6.74 (m, 1H, furyl), 4.20 (q, J = 7.2 Hz, 2H, OCH ),
1
2
3
.34 (t, J = 7.2 Hz, 3H, CH CH ); C NMR (CDCl , 75 MHz) d: 165.3, 158.2,
2
3
3
54.7, 146.3, 117.5, 111.6, 108.4, 106.3, 57.2, 17.3; HRMS: calcd for C10H9NO3:
91.3127, found: 191.3571.
2
-cyano-3-pentyl-acrylonitrile (3r)
-
1 1
Liquid. IR: 3,025.2, 2,253.7, 1,621.3, 1,175.8, 976.3, 810 cm ; H NMR (CDCl ,
3
3
4
00 MHz) d: 0.94 (t, J = 6.5 Hz, 3H, CH ), 1.25–1.35 (m, 2H, CH ), 1.40–1.50 (m,
3 2
H, 2 9 CH ), 1.97–2.05 (m, 2H, CH ), 7.66 (t, J = 10.0 Hz, 1H, CH = C(CN) );
2
2
2
1
3
C NMR (CDCl , 75 MHz) d: 14.21, 23.32, 25.01, 29.34, 32,97, 79.81, 119.26,
3
1
67,10; HRMS: calcd for C H N : 148.2377, found: 148.2495.
9
12 2
2
-cyano-3-pentyl-acrylonitrile (3s)
-
1
1
Liquid. IR: 3,020.7, 2,231.6, 1,625.3, 1,157.2, 836 cm
3
;
H NMR (CDCl3,
00 MHz) d: 1.42–1.56 (m, 2H, CH ), 1.98–2.23 (m, 4H, 2 9 CH ), 7.31 (t,
2
2
1
3
J = 10.0 Hz, 2H, 2 9 CH = C(CN)2); C NMR (CDCl , 75 MHz) d: 26.08,
3
2
9.16, 81.71, 119.63, 167,25; HRMS: calcd for C H N : 196.2175, found:
11 8 4
1
96.2411.
Acknowledgments We appreciate the financial support provided by the Natural Science Fund of Anhui
Province Education Office (KJ2011z050), the Natural Science Foundation of China (20771004/B0101),
and the Anhui Key Laboratory of Advanced Building Materials.
References
1
2
3
4
5
6
7
8
. G. Jones, The Knoevenagel condensation. Org. React. 15, 204 (1967)
. Y. Kubota, Y. Nishizaki, Y. Sugi, Chem. Lett. 29, 998 (2000)
. P.S. Rao, R.V. Venkataratnam, Tetrahedron Lett. 32, 5821 (1991)
. D. Prajapati, J.S. Sandhu, J. Chem. Soc. Perkin Trans. 1 1, 739 (1993)
. W. Lehnert, Tetrahedron Lett. 54, 4723 (1970)
. F. Texier-Boullet, A. Foucaud, Tetrahedron Lett. 23, 4927 (1982)
. V.S. Rajasekhar Pullabhotla, A. Rahman, S.B. Jonnalagadda, Catal. Commun. 10, 365 (2009)
. H. Moison, F. Texier-Boullet, A. Foucaud, Tetrahedron 43, 537 (1987)
123

402
S. Yuan et al.
9. J.A. Cabello, J.M. Campelo, A. Garcia, D. Luna, J.M. Marinas, J. Org. Chem. 49, 5195 (1984)
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
0. G. Dai, D. Shi, L. Zhou, Y. Huaxue, Chin. J. Appl. Chem. 12, 104 (1995)
1. S. Sebti, A. Smahi, A. Solhy, Tetrahedron Lett. 43, 1813 (2002)
2. L.D. Mohit, J.B. Pulak, Tetrahedron Lett. 46, 6453 (2005)
3. A. Maadi, C.L. Matthiesen, P. Ershadi, J. Baker, D.M. Herron, J. Chem. Cryst. 33, 757 (2003)
4. M.J. Climent, A. Corma, R. Guil-Lopez, S. Iborra, J. Primo, Catal. Lett. 59, 33 (1999)
5. E. Angeletii, C. Canepa, G. Martinetti, P. Venturello, J. Chem. Soc. Perkin Trans. 1 105, 105 (1989)
6. J. Simpson, D.L. Rathbone, D.C. Billington, Tetrahedron Lett. 40, 7031 (1999)
7. B.M. Choudary, M.L. Kantam, V. Neeraja, K.K. Rao, Green Chem. 3, 257 (2001)
8. Y.V.S. Rao, D.E. De Vos, P.A. Jacobs, J. Org. Chem. 64, 1033 (1999)
9. A. Ramani, B.M. Chanda, S. Velu, S. Sivasanker, Green Chem. 1, 163 (1999)
0. R.M. Kumbhare, M. Sridhar, Catal. Commun. 9, 403 (2008)
1. R. Trotzki, M.H. Hoffmann, B. Ondruschka, Green Chem. 11, 767 (2009)
2. K. Mogilaiah, H.S. Babu, K. Vidya, K.S. Kumar, Indian J. Chem. 48, 390 (2010)
3. S. Mallouk, K. Bougrin, A. Laghzizil, R. Benhida, Molecules 15, 813 (2010)
4. X.S. Wang, J.T. Li, W.Z. Yang, T.S. Li, Ultrason. Sonochem. 9, 159 (2002)
5. P. De la Cruz, E. D ´ı ez-Barra, A. Loupy, F. Langa, SFSDF. Tetrahedron Lett. 37, 1113–7879 (1996)
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