Sodium benzoate as a green, efficient, and recyclable catalyst for knoevenagel condensation

Article abstract of DOI:10.1080/00397911.2011.574245

Sodium benzoate was utilized as a novel efficient and green catalyst for the Knoevenagel condensation of aldehydes with active methylene compounds such as ethyl cyanoacetate and malononitrile to afford substituted olefins through the conventional stirring

Full text of DOI:10.1080/00397911.2011.574245

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Sodium Benzoate as a Green, Efficient,
and Recyclable Catalyst for Knoevenagel
Condensation
Qing Liu a & Hong-Mei Ai b
a Department of Chemistry and Environmental Science, Taishan
University, Tai'an, China
b Shandong University of Science and Technology, Tai'an, China
Available online: 10 Jan 2012
To cite this article: Qing Liu & Hong-Mei Ai (2012): Sodium Benzoate as a Green, Efficient, and
Recyclable Catalyst for Knoevenagel Condensation, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 42:20, 3004-3010
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Synthetic Communications1, 42: 3004–3010, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.574245
SODIUM BENZOATE AS A GREEN, EFFICIENT, AND
RECYCLABLE CATALYST FOR KNOEVENAGEL
CONDENSATION
Qing Liu1 and Hong-Mei Ai2
1Department of Chemistry and Environmental Science, Taishan University,
Tai’an, China
2Shandong University of Science and Technology, Tai’an, China
GRAPHICAL ABSTRACT
Abstract Sodium benzoate was utilized as a novel efficient and green catalyst for the Knoe-
venagel condensation of aldehydes with active methylene compounds such as ethyl cyanoa-
cetate and malononitrile to afford substituted olefins through the conventional stirring or
under ultrasounic irradiation. Improvements were observed by carrying out the reactions
under ultrasound irradiation. The reaction proceeded smoothly under mild conditions at
room temperature, and the products were obtained in excellent yields within short times:
The catalyst remains active and exhibits no substantial loss of activity for up to four reac-
tion cycles.
Keywords Catalysis; Knoevenagel; sodium benzoate; ultrasound irradiation
INTRODUCTION
Sodium benzoate is a common, safe food preservative and antimicrobial agent.
Sodium benzoate works well in acidic media to inhibit yeasts, molds, and bacterial
growth; is classified in the United States as Generally Recognized as Safe (GRAS),
and is used in food up to the maximum permitted level of 0.1%.[1] From Microtox
studies, the toxicity, in terms of the concentration that eliminated 50% of bacterial
population or EC50, of sodium benzoate was determined to be ꢀ 560 mg=L,[2] which
was three to five orders of magnitude less than that of tributyltin (TBT) (ꢀ0.01–
0.02 mg=L). Recognizing the commercial availability and low cost of sodium
Received September 30, 2010.
Address correspondence to Qing Liu, Department of Chemistry and Environmental Science,
Taishan University, Tai’an 271021, China. E-mail: sdsslq@163.com
3004

SODIUM BENZOATE AS GREEN CATALYST
3005
benzoate, it is used in a variety of products, such as cosmetics and pharmaceuticals,
but more commonly in foods such as soda and fruit juice to preserve freshness.[3]
However, its catalytic ability has been neglected for a long time. Sodium benzoate
has been reported as a catalyst in only one organic reaction to our knowledge.[4]
Therefore, the study of sodium benzoate as an environmentally benign catalyst is
in demand.
The Knoevenagel condensation is one of the most important reactions in
organic synthesis for carbon–carbon bond formation. It is usually performed in
organic solvents in the presence of common bases.[5] In recent years, various catalysts
have been employed to catalyze this reaction, each affording variable yields of Knoe-
venagel condensation compounds in solution or under solvent-free conditions. Using
the methods indicated previously, there are still some limitations which exist, such as
the long reaction time; the highly corrosive, expensive, and large amounts of cata-
lysts needed; and the strict reactive condition (N2 atmosphere or high tempera-
ture).[6,7] Hence, the introduction of efficient and new methods based on green
methodology is still of interest.
Ultrasound has increasingly been used in organic synthesis in the past three
decades. Compared with traditional methods, this method is more convenient and
easily controlled. A large number of organic reactions can be carried out in greater
yield, shorter reaction time, or milder conditions under ultrasonic irradiation.[8] We
report here an efficient condensation between active methylene compounds and vari-
ous aromatic aldehydes catalyzed by sodium benzoate through conventional stirring
(method A) or under ultrasounic irradiation (method B).
RESULTS AND DISCUSSION
At the begining, to evaluate the effect of the amount of catalyst on Knoevena-
gel condensation, we investigated its efficiency in a model reaction between benzal-
dehyde and malononitrile through method A. The yield was 96.7%, when sodium
benzoate was 1 mol% (Table 1, entry 3, and Scheme 1). There was no obvious
increase in the yield when more catalyst was added. The decrease in reactivity with
the decrease in the amount of sodium benzoate also shows that the Knoevenagel
condensation is a base-catalyzed reaction in the procedure described in this study.
To investigate the influence of the solvents, the model reaction was carried out
through method A in various solvents and also under solvent-free conditions. As
shown in Table 2, in comparison to conventional methods in solvent the yield of
Table 1. Effect of catalyst amount on Knoevenagel condensation of
benzaldehyde with malononitrile through method A
Entry
Amount (mol %)
Time (min)
Yield (%)a
1
2
3
4
5
0.25
0.5
1
27
22
15
15
13
94.3
96.7
96.7
95.5
96.5
2
5
aIsolated yield.

3006
Q. LIU AND H.-M. AI
Scheme 1. Knoevenagel condensation of benzaldehyde with malononitrile with different amounts of
sodium benzoate.
the reaction under solvent-free condition was greater and the reaction time was
shorter (Scheme 2). The reaction also proceeded well in ethanol, whereas in the other
solvents the reaction proceeded slowly. Consequently, the remainder of reactions
through both method A and method B were carried out under solvent-free conditions.
We also observed the effect of frequency of ultrasounic irradiation on the
Knoevenagel condensation of furfural with ethyl cyanoacetate. The reaction rate
was compared at 45, 80, and 100 kHz having the same output power of 300 W. Com-
pared to the reaction without ultrasounic irradiation (Table 2, entry 6), in the pres-
ence of ultrasound the yield was 98.7% only after 10 min for 45 kHz (Table 2, entry
7). Experiments performed with variable frequency (80 and 100 kHz) showed the
same trend. These facts mean that ultrasound could enhance this reaction, catalyzed
by sodium benzoate, and there was an optimum frequency of 45 kHz for effective
Knoevenagel condensation. As a result, further experiments were carried out with
45-kHz ultrasounic irradiation.
After optimizing the reaction conditions, aromatic aldehydes were treated with
various active methylene compounds such as ethyl cyanoacetate and malononitrile in
Table 2. Effect of reaction conditions on Knoevenagel condensation catalyzed by sodium benzoate
Entry
Solventa
Ultrasound (kHz)
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
9
C2H5OH
CH3CN
THF
–
–
15
50
96.4
85.1
96.3
76.9
0
–
240
100
600
15
1, 4-Dioxane
Acetone
–
–
Solvent-free
Solvent-free
Solvent-free
Solvent-free
–
96.7
98.7
98.3
96.3
45
80
100
10
12
13
aThe reaction was carried out in 2 mL of solvent.
bIsolated yield.
Scheme 2. Knoevenagel condensation of benzaldehyde with malononitrile under different reaction
conditions.

SODIUM BENZOATE AS GREEN CATALYST
3007
Scheme 3. Knoevenagel condensations of aldehydes with active methylene compounds catalyzed by
sodium benzoate.
the presence of sodium benzoate under ultrasounic irradiation or through conven-
tional stirring (Scheme 3). All of the comparative results are shown in Table 3.
The reactions were first carried out through the conventional stirring under
solvent-free conditions at room temperature. As shown in Table 3, the correspond-
ing products were obtained in good to excellent yields in several minutes except for
the condensation of ethyl cyanoacetate.
The condensation reactions also were carried out under ultrasounic irradiation
at room temperature. As seen in Table 3, the reaction times were reduced and most
of the yields were improved under ultrasound.
We found that the reaction proceeded much faster with acidic malononitrile
than with ethyl cyanoacetate. The aldehydes, containing electron-donating or electron-
withdrawing groups, all gave the desired products in excellent yields in short times
(from 7 to 60min through method A and from 5 to 40min through method B)
(Table 3, entries 1–7). Compared to the Knoevenagel reactions of malononitrile with
aromatic aldehydes, the reactions of ethyl cyanoacetate with the same aromatic
aldehydes needed longer time. However, both the conventional magnetic stirring
and the ultrasounic irradiation afforded the desired arylmethylenemalonitriles and
ethyl a-cyanocinnamates as the single products. The results indicate that only E
isomers of the olefinic products were produced when ethyl cyanoacetate was used.
Table 3. Knoevenagel condensation catalyzed by sodium benzoate under ultrasound irradiation or
through conventional stirring
Time (min)
Yield (%)c
Aa Bb
M.p. (ꢁC)
Entry
R
X
Compound
Aa
Bb
Found
Reported
1
2
C6H5
2-Furyl
CN
CN
3a
3b
3c
3d
3e
3f
15
13
10
10
5
96.7 98.7
90.1 96.2
87.2 90.8
82–83
65–66
93–95
82–83[9]
65–66[9]
95–96[10]
3
2-ClC6H4
2, 4-Cl2C6H3
4-CH3OC6H4
4-OHC6H4
Vanillin
CN
CN
7
14
4
7
95.1 98.3d 154–155 154–155[11]
5
CN
CN
15
23
7
86.8 93.7
111–113 110–112[9]
6
10
40
210
108
192
98.8 98.2d 185–186 183–184[12]
85.8 92.3d 133–135 135–136[10]
7
CN
COOEt
3 g
3 h
3i
60
8
2-Furyl
350
180
360
95.0 95.9
98.2 99.0
84.8 90.4
86–87
83–84
164–167 162–164[9]
86–87[9]
9
10
2, 4-Cl2C6H3 COOEt
4-OHC6H4 COOEt
83–84[10]
3j
aA, without ultrasound irradiation.
bB, under ultrasound irradiation.
cIsolated yield.
dUnder ultrasound irradiation in 2 mL C2H5OH.

3008
Q. LIU AND H.-M. AI
Table 4. The reuse of sodium benzoate
Cycle
1
2
3
4
Yield (%)a
aIsolated yield.
98.6
98.0
97.5
97.3
Table 5. Knoevenagel condensation of benzaldehyde with malononitrile catalyzed by different catalysts
Entry
Catalyst and Conditions
Amount (mol%)
Time (min)
Yield (%)a
Ref.
b
1
2
3
4
5
6
C6H5CO2Na=solvent-free
MgF2=EtOH
1
31
30
0.8
10
15
10
150
12
98.7
93
-
13
14
15
16
17
I2=K2CO3=EtOH
[2-aemin][PF6]=H2O
HEAPs=H2O
80
92
20
10
95
100
[C4dabco][BF4]=H2O
<1
aIsolated yield.
bUnder ultrasound irradiation.
Mention must be made here that 2 mL C2H5OH had to be added when solid
aldehydes were treated with malononitrile under ultrasounic irradiation conditions
(Table 3, entries 4,6, and 7). The volume of malononitrile was so small that the
aldehydes, malononitrile, and catalyst were difficult to mix thoroughly under ultra-
sounic irradiation without stirring, and this may lead to prolonged reaction times.
The miscibility of sodium benzoate with water made the workup process quite
easy, as the catalyst could be removed from the product simply by washing the pro-
duct with 5% aqueous alcohol. The catalyst in the aqueous phase could be recovered
by removing the water under vacuum and then washing the catalyst with acetone and
drying it at rt. Catalyst reusability was assessed in the reaction of benzaldehyde with
malononitrile under ultrasound irradiation. Table 4 shows the catalyst can be reused
four times without significant decrease of the reactivity.
To show the merit of sodium benzoate in comparison with the other catalysts
used for the same reaction, we have tabulated some of the results in Table 4. As is
evident from the results, the required amount for the most catalysts used for this pur-
pose is more than 1 mol% and also the required reaction time is longer. Mention
must be made here that some catalysts are expensive, complex, or unavailable and
solvents are necessary.
CONCLUSION
In conclusion, we have demonstrated a facile and efficient method for the
Knoevenagel condensation of aromatic aldehydes with active methylene compounds
under both ultrasounic irradiation and conventional stirring conditions in the pres-
ence of sodium benzoate. Improvements in rates and yields of the reactions were
observed by carrying out the reactions under ultrasounic irradiation. The catalyst
remained active and exhibited no substantial loss of activity for up to four reaction

SODIUM BENZOATE AS GREEN CATALYST
3009
cycles. The attractive features of this procedure were the mild reaction conditions,
good yields, cleaner reaction profiles, and operational simplicity, all of which make
it a useful and attractive strategy for the preparation of substituted olefins.
EXPERIMENTAL
All reagents were purchased and used without further purification. Melting
points were determined using an XT-4 micro-melting-point apparatus. Infrared
(IR) spectra were recorded on a Nicolet Avatar 360 Fourier-transform instrument
.
in KBr with absorption in cmÀ1 1HNMR spectra were recorded on a Bruker
ARX-300 spectrometer using CDCl3 as solvent and tetramethylsilane (TMS) as
the internal standard. Ultrasonication was performed in a KQ-300VDE ultrasounic
cleaner with frequencies of 45, 80, and 100 kHz and an output power of 300 W.
General Procedure for Knoevenagel Condensation Through Method A
Aldehyde (10 mmol) and the active methylene compound (10 mmol) were
mixed thoroughly, and then 0.1 mmol of sodium benzoate was added. The reaction
mixture was stirred for the specified time at room temperature. After completion of
the reaction, the reaction mixture was treated with cold 5% aqueous alcohol (30 mL).
The product was filtered and dried, and, in general, no further purification method
was required. All the products were previously reported and were characterized by
1
comparing mp, IR, and H NMR with litrature data.
General Procedure for Knoevenagel Condensation Through Method B
Aldehyde (10 mmol), active methylene compound (10 mmol), and 0.1 mmol of
sodium benzoate were put in a flask. The flask was located at the maximum energy
area in the ultrasonic cleaner and addition or removal of water was used to control
the temperature of the water bath at room temperature. After completion of the
reaction, the subsequent steps were the same as in method A.
ACKNOWLEDGMENTS
This work was supported by Shandong Province Natural Science Foundation
(ZR2010BL017). We gratefully thank Prof. Heng Jiang for his kind help and
Taishan University for financial support.
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