Synthesis of arylmethylenemalononitriles catalyzed by KF-Al 2O3 under ultrasound

Article abstract of DOI:10.1071/CH03308

Knoevenagel condensation of malononitrile with aromatic aldehydes catalyzed by KF-Al₂O₃ under ultrasound irradiation in anhydrous ethanol results in the formation of arylmethylenemalononitriles in 73-97% yields within 15-60min. CSIRO

Full text of DOI:10.1071/CH03308

Short Communication
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2005, 58, 231–233
Synthesis of Arylmethylenemalononitriles Catalyzed by KF–Al O
2
3
under Ultrasound
Ji-Tai Li,A,B Guo-Feng Chen, Shu-Xiang Wang, Lin He, and Tong-Shuang Li
A
A
A
A
A
College of Chemistry and Environmental Science, Hebei University, Key Laboratory of Analytical
Science and Technology of Hebei Province, Baoding 071002, China.
Corresponding author. Email: orgsyn@mail.hbu.edu.cn
B
Knoevenagel condensation of malononitrile with aromatic aldehydes catalyzed by KF–Al2O3 under ultrasound
irradiation in anhydrous ethanol results in the formation of arylmethylenemalononitriles in 73–97% yields within
1
5–60 min.
Manuscript received: 15 June 2004.
Final version: 8 December 2004.
Arylmethylenemalononitriles are used as precursors in the
synthesis of potentially bioactive pyrimidine derivatives.
α-cyanocinnamates to afford the desired products in higher
[
1]
[18,19]
yields.
In continuation of a broad programme pursued
Preparation of arylmethylenemalononitriles is usually
achieved by Knoevenagel condensation of malononitrile
with various aromatic aldehydes under conventional heat-
ing using organic bases (primary, secondary, and tertiary
in our laboratory into ultrasound-induced organic reactions,
we herein wish to report a facile sonochemical synthesis of
arylmethylenemalononitriles catalyzed by KF–Al2O3.
Most products described herein were previously reported
[
2]
[3–11]
amines, ammonia or ammonium salts) as catalysts. Alter-
in the literature.
As shown in Scheme 1 and Table 1,
[
3]
natively, the use of Al2O3, silica gel functionalized with
the KF–Al2O3 catalyzed condensation of malononitrile with
a series of aromatic aldehydes in anhydrous ethanol under
ultrasound irradiation afforded arylmethylenemalononitriles
in excellent yields. However, the most dramatic changes
observed were with regard to reaction time. In the reaction
[4]
[5]
[6]
[7]
[8]
amino groups, ZnCl2, CdI2, K3PO4, USY zeolite,
[9]
[10]
xonotlite,
and KF–Al2O3,
has also been reported.
Recently, urotropine coupled with microwave irradiation has
been shown to be an efficient method for the synthesis
[11]
[8]
of arylmethylenemalononitriles.
Furthermore, Ren et al.
catalyzed by USY zeolite, 3a was obtained in 92% yield
have reported that the Knoevenagel condensation reaction
of aromatic aldehydes with malononitrile proceeded in good
after being heated at reflux in benzene for 12 h, whereas the
present procedure afforded 3a in 90% yield within 20 min
[12]
◦
yields in the absence of solvents and catalysts.
In the last two decades, ultrasound has become widely
of being stirred at 22–25 C. Similarly, in the reaction cat-
[
9]
alyzed by xonotlite, 3d and 3l were obtained after 24 h in
65 and 70% yield, respectively, whereas the present procedure
afforded 3d and 3l in 97 and 92% yield within 20–40 min.
Moreover, although the condensation reaction was carried
out at room temperature, Michael addition products were not
detected. It is apparent that complete condensation can be
achieved under milder conditions and in higher yields upon
ultrasound irradiation and catalysis with KF–Al2O3.
[13]
used in organic synthesis.
In comparison with traditional
methods, this procedure is more convenient and easily con-
trolled. A large number of organic reactions can be carried
out in higher yields, shorter reaction times, and milder
[14,15]
conditions under ultrasound.
Recently, our laboratory
has reported the pyridine-catalyzed condensation of ethyl
cyanoacetate with various aromatic aldehydes under ultra-
[16]
sound irradiation.
The results were better than those
A KF–basic Al2O3 catalyst system was also trialed for the
condensation of 2-nitroarylmethylenemalononitrile 3g, but
the yield (69%) was found to be lower than that obtained
for the reaction catalyzed by KF–Al2O3. As shown by the
formation of 2-nitroarylmethylenemalononitrile 3g, the KF–
Al2O3 catalyst can be reused twice upon being washed with
obtained under conventional heating conditions, but it was
found that the catalyst could not be recycled.
Catalysts and reagents supported on inorganic substrates
have received increasing attention in recent years as a means
[17]
to develop more convenient substrates.
In particular, KF–
Al2O3 has been used as an efficient catalyst in a number of
organic reactions with the advantage that it is reusable and
has minimal environmental impact. As reported in previous
papers, potassium fluoride adsorbed onto alumina has been
used as a catalyst in the preparation of chalcones and ethyl
CN
CN
CN
CN
KF–Al O
2
3
ArCHO ϩ H C
ArCH
C
2
)))
Scheme 1.
©
CSIRO 2005
10.1071/CH03308
0004-9425/05/030231

2
32
J.-T. Li et al.
Table 1. Synthesis of arylmethylenemalononitriles under ultrasound irradiation
◦
YieldA [%] (lit.)
◦
Compound
Ar
t [min]
T [ C]
Mp [ C] (lit.)
[
[
12]
12]
[12]
3
3
3
3
3
3
3
a
b
c
d
e
f
C6H5
2-ClC6H4
3-ClC6H4
4-ClC6H4
2,4-Cl2C6H3
3,4-(OCH2O)C6H3
2-O2NC6H4
20
20
30
20
60
20
15
15
15
15
15
15
15
15
35
20
20
25
20
40
40
35
22–25
23–26
24–30
20–24
22–29
18–22
23–25
23–25
23–25
23–25
23–25
23–25
23–25
23–25
23–25
21–24
22–24
25–29
24–26
19–26
19–26
19–26
90 (68
95 (95
83
97 (85
89
)
)
87–88 (82–83
97–98 (94–95
121–122
)
)
[12]
[
12]
[12]
)
163–164 (162–163
)
155–156
[
[
12]
10]
[12]
[10]
94 (80
91 (97
)
)
205–206 (201–202
144–145 (139–140
)
)
g
B
2-O2NC6H4
2-O2NC6H4
2-O2NC6H4
2-O2NC6H4
2-O2NC6H4
2-O2NC6H4
2-O2NC6H4
2-O2NC6H4
90
89
86
85
69
79
85
66
–
–
–
–
–
–
–
–
C
D
E
F
G
H
I
[
[
12]
[12]
[12]
3
3
3
3
3
h
i
j
k
l
3-O2NC6H4
4-O2NC6H4
2-HOC6H4
4-HOC6H4
4-CH3C6H4
84 (88
73 (40
91
)
109–110 (103–104
166–167 (161–162
163–164
193–194 (187–188
139–140 (134–135
139–140
[12]
119–120 (113.5–114 )
)
)
9]
)
[
[
12]
12]
[12]
[12]
90 (83
92 (96
)
)
)
)
B
4
-CH3C6H4
95
[
12]
3
m
4-CH3OC6H4
90 (94
)
A
B
C
Isolated yield based on aromatic aldehydes. First recycled KF–Al2O3 was used. Second recycled
KF–Al2O3 was used. At 40 kHz. E At 59 KHz. KF/basic alumina was used as catalyst. G KF as catalyst.
D
F
H
I
Al2O3 as catalyst. Stirred for 35 min without ultrasound.
◦
dichloromethane and reactivated at 120 C for 4 h without
significant decrease in activity (90% on the second run and
cleaner, in which the surface of reactants is slightly lower than the level
of the water. The reaction temperature was controlled by addition or
removal of water from the ultrasonic bath.
8
9% on the third run).
We also monitored the effects of using different fre-
Preparation of the Catalyst (KF–Al2O3)
quencies of ultrasound irradiation on the reaction of 2-
nitrobenzaldehyde with malononitrile and found that higher
yields were obtained at lower frequencies. For example, when
thefrequencywas25 kHz, thedesiredproductwasobtainedin
Neutral aluminium oxide (30 g) was added to a solution of KF (20 g)
in water (80 mL) and the resultant reaction mixture was stirred at 65–
◦
7
5 C for 1 h. The water was then removed under reduced pressure and
◦
the free-flowing powder was dried at 120 C for 4 h. The content of KF
was determined to be about 40%.
9
1% yield after 15 min, while upon sonication in an ultrasonic
cleaner with a frequency of 59 kHz, the condensation reaction
afforded the desired product in only 85% yield after 15 min.
As a result of these findings, the condensation catalyzed by
KF–Al2O3 was carried out under 25 kHz irradiation.
In conclusion, we have found a practical Knoevenagel
condensation procedure for the preparation of arylmethylene-
malononitrilescatalyzedbyKF–Al2O3 underultrasoundirra-
diation. Our procedure is characterized by milder conditions,
shorter reaction times, higher yields, and the involvement of
a non-toxic and inexpensive catalyst.
General Procedure
Aromatic aldehydes 1 (2.0 mmol) and malononitrile 2 (2.0 mmol) were
dissolved in anhydrous ethanol (2 mL) in a 50 mL conical flask. The
KF–Al O3 (300 mg) was then added and the mixture was irradiated
2
in the water bath of an ultrasonic cleaner at the temperature and period
indicated inTable 1 (sonication was continued until crystals appeared or
the aromatic aldehydes disappeared byTLC).The mixture was dissolved
in CH2Cl2 and the catalyst was removed by filtration and washed with
further portions of CH2Cl2. The solvent was then evaporated under
reduced pressure and the resultant crude products were recrystallized
from 95% ethanol. The authenticity of the products was established by
spectroscopic data and by comparing their melting points with literature
values.
Experimental
Materials and Measurements
Compound 3c
Liquid aldehydes were purified by distillation before use. Melting points
were uncorrected. IR spectra were recorded on a Bio-Rad FTS-40
spectrometer (KBr). H NMR spectra were measured on a Bruker
−
1
Isolated as white needles. νmax (KBr)/cm 2230 (CN). δH 7.50–7.87
(5H, m, ArH and CH). m/z 188 (83%, M ), 163 (8), 161 (28), 137 (32),
1
+•
AVANCE-400 (400 MHz) spectrometer using TMS as internal standard
and CDCl3 as solvent. Mass spectra were determined on a VG-7070E
spectrometer (EI, 70 eV). Sonication was performed in a Shanghai
Branson-CQX ultrasonic cleaner (25 kHz and a nominal power of
126 (19), 137 (32), 126 (19), 100 (17), 87 (12).
Compound 3e
2
50W) and an SK 250 LH ultrasonic cleaner (40 and 59 kHz, and a
Isolated as white needles. νmax (KBr)/cm 1 2250 (CN). δH 7.45–8.18
−
(3H, m, ArH), 8.21 (s, CH). m/z 222 (100%, M ), 187 (72), 152 (16),
124 (17), 99 (34), 85 (15), 75 (35), 61 (22), 50 (36), 40 (98).
+
•
nominal power of 250W; Shanghai Kudos Ultrasonic Instrument Co.).
The reaction flasks were located in the maximum energy area in the

Synthesis of Arylmethylenemalononitriles
233
Compound 3j
[7] Y. Q. Li, J. Chem. Res., Synop. 2000, 524.
−
Isolated as yellow needles. νmax (KBr)/cm 1 2200 (CN). δH 7.12–7.63
(
(
[8] Q. L. Wang,Y. D. Ma, B. J. Zuo, Synth. Commun. 1997, 27, 4107.
[9] S. Chalais, P. Laszlo, A. Mathy, Tetrahedron Lett. 1985, 26, 4453.
doi:10.1016/S0040-4039(00)88928-5
+
•
4H, m, ArH), 7.39 (s, CH), 8.85 (s, OH). m/z 170 (74%, M ), 144
100), 113 (39), 87 (25), 76 (13), 63 (26), 51 (28), 39 (40).
[
[
[
10] L. H. Zhou, Y. Gao, D. Q. Shi, G. Y. Dai, Huaxueshiji 1998,
2
0, 135.
11] Y. Q. Peng, G. H. Song, X. H. Qian, J. Chem. Res., Synop.
001, 188.
Acknowledgment
2
The project was supported by the Educational Ministry of
China and Natural Science Foundation of Hebei Province
12] Z. J. Ren, W. G. Cao, W. Q.Tong, Synth. Commun. 2002, 32, 3475.
doi:10.1081/SCC-120014780
(
203107), China.
[13] (a) J. L. Luche, Synthetic Organic Sonochemistry 1998, p. 3
(
(
(
Plenum: New York, NY).
b) T. J. Mason, D. Peter, Practical Sonochemistry, 2nd edn 2002
Ellis Horwood: London).
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