Solvent-free knoevenagel condensation over cobalt hydroxyapatite

Article abstract of DOI:10.1080/00397910903531714

The Knoevenagel condensation between various aldehydes (benzaldehyde, 1-naphthaldehyde, p-bromobenzaldehyde and p-methoxybenzaldehyde) and esters (ethylcyanoacetate, ethylacetoacetate and diethylmalonoester) was carried out under solvent free condition in the presence of cobalt hydroxyapatite (CoHAp), as a catalyst. Good to excellent yields (35-96%) were obtained. The catalyst is found to be superior over fluorapatite and several other heterogeneous catalysts. The catalyst can be recycled at least 3 times. Copyright

Full text of DOI:10.1080/00397910903531714

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Solvent-Free Knoevenagel Condensation
over Cobalt Hydroxyapatite
a
a
Manoharan Karuppiah Pillai , Sooboo Singh & Sreekanth B.
a
Jonnalagadda
a
School of Chemistry, University of KwaZulu-Natal, Durban, South
Africa
Published online: 09 Nov 2010.
To cite this article: Manoharan Karuppiah Pillai , Sooboo Singh & Sreekanth B. Jonnalagadda (2010)
Solvent-Free Knoevenagel Condensation over Cobalt Hydroxyapatite, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:24, 3710-3715,
DOI: 10.1080/00397910903531714
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Synthetic Communications , 40: 3710–3715, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903531714
SOLVENT-FREE KNOEVENAGEL CONDENSATION
OVER COBALT HYDROXYAPATITE
Manoharan Karuppiah Pillai, Sooboo Singh, and
Sreekanth B. Jonnalagadda
School of Chemistry, University of KwaZulu-Natal, Durban, South Africa
The Knoevenagel condensation between various aldehydes (benzaldehyde, 1-naphthaldehyde,
p-bromobenzaldehyde and p-methoxybenzaldehyde) and esters (ethylcyanoacetate, ethylace-
toacetate and diethylmalonoester) was carried out under solvent free condition in the presence
of cobalt hydroxyapatite (CoHAp), as a catalyst. Good to excellent yields (35–96%) were
obtained. The catalyst is found to be superior over fluorapatite and several other heterogeneous
catalysts. The catalyst can be recycled at least 3 times.
Keywords: Cobalt hydroxyapatite; environment friendly; Knoevenagel condensation; solvent-free
condition
INTRODUCTION
The Knoevenagel condensation is an important carbon-carbon double bond
forming reaction and used widely in the synthesis of intermediates or end products
[
for pharmaceuticals, perfumes, polymers, etc. The reaction is usually catalysed by
1]
[
bases such as ammonia, primary and secondary amines, quaternary ammonium
2]
[
3,4]
[5–7]
[8]
catalysis containing acid-base sites, etc. and usually
salts
Lewis acids,
carried out under homogeneous conditions, which require organic solvent and this
generates a large volume of solvent waste. For the standpoint of sustainable environ-
ment and minimising pollution, solvent free heterogeneous catalysts have been
receiving increasing attention. Since, these heterogeneous catalysts not only avoid
the use of organic solvent but also suppress side reactions such as self condensation,
[
9]
oligomerisation etc. resulting in better selectivity and product yield. In recent years,
[
10–13]
therefore, the use of heterogeneous catalysts,
very much sought after in industry. The use of fluorapatite was reported earlier as a
their recovery and reusability are
[
14]
heterogeneous catalyst for Knoevenagel condensation.
characterized several hydroxyapatite catalysts and used them for the oxidation of
pentane, n-hexane, etc. We envisioned that cobalt hydroxyapatite, CoHAp could
be extended for Knoevenagel condensation to form various alkenes and the results of
We have synthesized and
[15]
Received August 5, 2009.
Address correspondence to Sreekanth B. Jonnalagadda, School of Chemistry, University of
KwaZulu-Natal, Westville Campus, Post Box X-54001, Durban 4000, South Africa. E-mail:
Jonnalagaddas@ukzn.ac.za
3
710

SOLVENT-FREE KNOEVENAGEL CONDENSATION
3711
that study are communicated herewith. CoHAp was synthesised by the procedure as
described in the literature.
[16]
RESULTS AND DISCUSSION
In the present study, we report the Knoevenagel condensation between various
aldehydes (benzaldehyde, 1a; 1-naphthaldehyde, 1b; p-bromobenzaldehyde, 1c and
p-methoxybenzaldehyde, 1d) and esters (ethylcyanoacetate, 2a; ethylacetoacetate,
2
b and diethylmalonoester, 2c) under solvent free condition in the presence of
CoHAp as a catalyst (Scheme 1). To investigate the effect and the role of catalyst
on the yield of products, each one of the reactions was carried out in triplicate by
varying the amounts of catalyst as 0.025, 0.05 and 0.100 g. For example, the reaction
of 1a with 2a was carried out by the use of 0.025, 0.05 and 0.100 g of catalyst
and respectively 45, 91 and 96% of yields of product 3a (Table 1) were obtained.
The same reaction was carried out under the similar reaction conditions without
the catalyst and it did not give product in the stipulated time period (5 min). These
results confirm the necessity of CoHAp as catalyst for the proposed reaction.
Further, it was also observed that a maximum yield of 96% of product 3a was
obtained by the use of 0.10 g of catalyst; however, the yield 91%, which was very
close to the maximum yield, was obtained by the use of 0.05 g of catalyst
(Table 1). This observation was noticed in all cases, (Table 1, Entry 2–12) and the
percentage yields of other condensation products, 3b–3l, under similar condition
and the time duration are given in Table 1.
In general the reactions were fast and the products were obtained in short
reaction time of 2 to10 min, except for the reaction of 1b with 2a–2c in which cases
it took about 60–90 min. Among the condensation reactions investigated, the
catalyst was very efficient towards i) the reactions of 1a with 2a, 2b and 2c
which gave the products 3a, 3e, and 3i in an excellent yields of 96%, 87%, and 92%
respectively; and ii) the reactions of 1d with 2a, 2b, and 2c, which gave the products
3
d, 3h, and 3l in an excellent yield of 91%, 88%, and 93% respectively. The reactions
of 1b with 2a, 2b, and 2c were moderately accelerated by the CoHAp which gave the
products 3b, 3f and 3j with a yield of 76, 62 and 82%, respectively. The catalyst
Scheme 1. Knoevenagel condensation.

3712
M. K. PILLAI, S. SINGH, AND S. B. JONNALAGADDA
Table 1. Synthesis of various alkenes, 3a-3l, by Knoevenagel condensation using CoHAp under solvent-
free condition
Amount of catalyst and yields
0.025 g
yield (time)
0.05 g
yield (time)
0.100 g
yield=(time)
Entry
Aldehydes
Esters
Products
1
2
3
4
5
6
7
8
9
benzaldehyde, 1a
2a
2a
2a
2a
2b
2b
2b
2b
2c
2c
2c
2c
3a
3b
3c
3d
3e
3f
45 (5)
42 (90)
35 (5)
47 (2)
61 (10)
41 (60)
39 (8)
47 (5)
51 (2)
53 (70)
46 (10)
48 (2)
91 (5)
72 (90)
44 (5)
85 (2)
80 (10)
55 (60)
56 (8)
84 (5)
85 (2)
78 (70)
49 (10)
87 (2)
96 (5)
76 (90)
49 (5)
91 (2)
87 (10)
62 (60)
60 (8)
88 (5)
92 (2)
82 (70)
56 (10)
93 (2)
1-naphthaldehyde, 1b
p-bromobenzaldehyde, 1c
p-methoxybenzaldehyde, 1d
benzaldehyde, 1a
1-naphthaldehyde, 1b
p-bromobenzaldehyde, 1c
p-methoxybenzaldehyde, 1d
benzaldehyde, 1a
3g
3h
3i
1
1
1
0
1
2
1-naphthaldehyde, 1b
p-bromobenzaldehyde, 1c
p-methoxybenzaldehyde, 1d
3j
3k
3l
Yields are in mol %; time is in minutes.
poorly accelerated the reactions of 1c with 2a, 2b, and 2c which gave the products 3c,
3
g, and 3k with a yield of 49%, 60% and 56%, respectively.
In order to test the reusability of CoHAp, the Knoevenagel condensation of 1a
with 2a was carried out in the presence of 0.100 g of catalyst. The catalyst was tested
for a total of five successive usages and the yields were very satisfactory for three suc-
cessive usages and gave the product 3a with a yield of 92%, 90%, and 86% respect-
ively. Thereafter, the yields were drastically lowered such that for the fourth and fifth
successive usages it gave only 62 and 44% of yields, respectively. In the fourth usage,
the recovered catalyst was about 50% (0.054 g) and if the catalyst is as efficient as
fresh it would have to yield as much as of 91%. However, the obtainment of 62%
of yield implied that the catalyst has lost its efficiency from the fourth usage
onwards. The probable reasons for this can be of twofold: i) apparently, the amount
of catalyst played an important role in the yield of products i.e., higher the amount
of catalyst, the higher is the yield of products. During recovery, a loss of about
1
0–15% of catalyst was observed in every successive cycle and that would be
Table 2. The catalytic activity of recycled CoHA
Knoevenagel condensation of 1a with 2a
P
catalyst (0.100 g) for the
Time
(min)
Yield
(mol%)
Recovery of
catalyst (wt%)
Cycle
1
2
3
4
5
5
5
5
5
5
93
90
86
62
44
84
75
62
54
40

SOLVENT-FREE KNOEVENAGEL CONDENSATION
3713
Table 3. Comparison of CoHAp catalysed Knoevenagel condensation of 1a with 2a
for the yields of product 3a with other heterogeneous catalysts
Entry
Catalyst
Time (min)
Yield (mol%)
1
2
3
4
5
6
7
8
9
CoHAp (0.100 g)
CoHAp (0.050 g)
5
5
96
91
37
95
55
72
86
80
32
78
91
Flourapatite (1.25 g) [14]
Flourapatite (1.25 g) [14]
Nickel hydroxyapatite (0.083 g) [15]
Zeolite (Znb) (0.100 g) [1]
15
90
1200
360
150
15
KF=Al
AlPO =Al
Resin [19]
Zeolite [20]
ZnCl [6]
2
O
3
[17]
4
O [18]
2 3
300
720
10
1
1
0
1
2
one of the reasons for the lower in yield in every successive cycle ii) another plausible
reason would be that the active sites on the surface of the catalyst might have slowly
poisoned due to interaction with products. The poisoning effect might have been
much more pronounced from fourth cycle onwards. Therefore, only 62% of yield
was obtained from 0.054 g of the recovered catalyst in fourth cycle which was
much lower than the yield of 91% obtained from 0.05 g of fresh catalyst, i.e., about
the same quantity of catalyst. Table 2 shows the percentage yield in every cycle and
the corresponding loss of an average of about 10–15% of catalyst in every successive
usage.
A literature survey of the yields reported for Knoevenagel condensation
reaction of 1a with 2a to give 3a using various heterogeneous catalyst materials
and solvent free conditions shows that CoHAp catalysed system proves superior
[
1,14,15,17–20]
than many others.
different catalysts under varied temperature conditions. The fluorapatite catalyst
Table 3 summarises the literature values of yields with
required 1.25 g (>1 mmol) to produce 37 and 95% yields of product 3a in 15 and
[
14]
9
0 min,
respectively. A meager quantity, 0.100 g (<0.1 mmol) and 0.05 g, of
CoHAp is required for producing, respectively, 96 and 91% yields of product 3a
in 5 min times.
EXPERIMENTAL
An equimolar quantity (2.0 mmol) of aldehydes (1a–1d) and esters (2a–2c) were
ꢀ
taken in a flask and the mixture was heated at 80 C for a while and then CoHAp
catalyst was added and stirred vigorously and left to stand. The products (3a–3l) were
extracted with chloroform and the catalyst was removed by simple filtration. The
products were separated by isolation method using column chromatography using
a 40 cm column packed with silica gel 60 (Merck, 0.063–0.200 micron) and eluted
the product mixture with solvents of increasing polarity, in the order hexane, chloro-
form and acetone. Each fraction was monitored through TLC. The pure compound
1
factions were isolated and were identified by H NMR spectroscopy, and then the
yields were calculated. The yields reported in the communication are in mol%;

3714
M. K. PILLAI, S. SINGH, AND S. B. JONNALAGADDA
the amount of the recovered catalyst is reported in wt%. All reagents used were of
Analytical grade reagents; p-methoxybenzaldehyde and 1-naphthaldehyde were pur-
chased from Sigma-Aldrich; benzaldehyde, ethylacetoacetate, p-bromobenzaldehye,
ethylcyanoacetate and diethylmalonoester were purchased from Merck. Silica gel 60
TLC plates were obtained from Merck, Darmstadt, Germany.
CONCLUSIONS
We have demonstrated the efficiency of CoHAp as catalyst for the Knoevenagel
condensation between various aldehydes (1a–1d) and esters (2a–2c) giving good to
excellent yields. The reactions were fast and carried under solvent free conditions.
CoHAp can replace the existing homogeneous catalyst as well as many of the hetero-
geneous catalysts with reasonable recovery and reusability and therefore ideal for
industrial applications.
ACKNOWLEDGMENTS
This research has been supported by a grant from National Research
Foundation and the University of KwaZulu Natal, Durban-Westville Campus.
Manoharan Karuppiah Pillai thanks the National Research Foundation and the
University of KwaZulu Natal for postdoctoral bursary.
REFERENCES
1
. Saravanamurugan, S.; Palanichamy, M.; Hartman, M.; Murugesan, V. Knoevenagel
condensation over b and Y zeolites in liquid phase under solvent free conditions.
Appl. Catal. A: General 2006, 298, 8–15.
2
3
. Cope, A. C. Organic Reactions; G. Jones Ed.; John Wiley and Sons: New York, 1967;
vol. 15, p. 204.
. Wang, S.; Ren, Z.; Cao, W.; Tong. The Knoevenagel condensation of aromatic aldehydes
with malononitrile or ethyl cyanoacetate in the presence of CTMAB in water. Synth.
Commun. 2001, 31, 673–677.
4. Jin, T. S.; Wang, X.; Liu, L. B.; Li, T. S. Clean synthesis of ethyl a-cyanocinnamates
catalysed by hexadecyltrimethyl ammonium bromide in aqueous media. J. Chem. Res.
2006, 6, 346–347.
5
. Attanasi, O.; Fillippone, P.; Mei, A. Effect of metal ions in organic synthesis. part XVI.
Knoevenagel condensations of aldehydes and Tosylhydrazones with 2,4-pentanedione by
copper (II) chloride-catalysed reaction. Synth. Commun. 1983, 13, 1203–1208.
. Shanthan Rao, P.; Venkatratnam, R. V. Zinc chloride as a new catalyst for Knoevenagel-
condensation. Tetrahedron Lett. 1991, 32, 5821–5822.
6
7
8
9
. Bao, W.; Zhnag, Y.; Wang, J. Aldol condensation of b-diketones and b-ketoesters with
aldehydes catalysed by samarium (III) iodide. Synth. commun. 1996, 26, 3025–3028.
. Reeves, R. L.; Patai, S. The Chemistry of Carbonyl Compounds; Interscience Publishers:
New York, 1996; p. 567.
. Zhnag, X.; Lai, E. S. M.; Martin-Aranda, R.; Yeung, K. L. An investigation of Knoevenagel
condensation reaction in microreactors using a new zeolite catalyst. Appl. Catal. A: General
2004, 261, 109–118.

SOLVENT-FREE KNOEVENAGEL CONDENSATION
3715
10. Balalaie, S.; Nemati, N. Ammonium acetate-basic alumina catalysed Knovenagel
condensation under microwave irradiation under solvent-free condition. Synth. Commun.
2000, 30, 869–875.
1
1
1. Wang, G. W.; Cheng, B. Solvent-free and aqueous Knoevenagel condensation of aromatic
ketones with malononitrile. ARKIVOC 2004, ix, 4–8.
2. Mogilaiah, K.; Prashanthi, M.; Reddy, G. R.; Reddy, C. S.; Reddy, N. V. Mocrowave
assisted Knovenagel condensation using sodium fluoride and lithium chloride as catalysts
under solvent free conditions. Synth. Commun. 2003, 33, 2309–2312.
1
1
3. Reddy, G. V.; Maitraie, D.; Narsaiah, M. B.; Rambabu, Y.; Rao, P. S. Mocrowave
assisted Knovenagel condensation: A facile method for the synthesis of chalcones. Synth.
Commun. 2001, 31, 2881–2884.
4. Sebti, S.; Nazih, R.; Tahir, R.; Salhi, L.; Saber, A. Fluorapatite: New solid catalyst of the
Knoevenagel reaction in heterogeneous media without solvent A. Appl. Catal. A: General
2000, 197, L187–L190.
1
1
5. Singh, S.; Jonnalagadda, S. B. Selective oxidation of n-pentane over V O supported on
2
5
hydroxyapatite. Catal. Lett. 2008, 126, 200–206.
6. Pullabhotla, V. S. S. R.; Rahman, A.; Jonnalagadda, S. B. Selective catalytic Knoevenagel
condensation by Ni–SiO supported heterogeneous catalysts: An environmentally benign
2
approach. Catal. Commun. 2009, 10, 365–369.
1
1
1
2
2
7. Opre, Z.; Grunwaldt, J. D.; Maciejewski, M.; Ferri, D.; Mallat, T.; Baiker, A. Promoted
Ru-hydroxyapatite: Designed structure for the fast and highly selective oxidation of
alcohols with oxygen. J. Catal. 2005, 230, 406–419.
8. Yamawaki, J.; Kawate, T.; Ando, T.; Hanafusa, T. Potassium fluoride on alumina:
An efficient solid base for elimination, addition and condensation. Bull. Chem. Soc.
Jpn. 1983, 56, 1885–1886.
9. Cabello, J. A.; Campelo, J. M.; Garcia, A.; Luna, D.; Marinas, J. M. Knoevenagel
condensation in the heterogeneous phase using aluminum phosphate-aluminum oxide
as a new catalyst. J. Org. Chem. 1984, 49, 5195–5197.
0. Saito, T.; Goto, H.; Honda, K.; Fujii, T. Acid-base catalysts derived from weakly
acidic ion exchange resin: Efficiency in the Knoevenagel condensation. Tetrahedron Lett.
1992, 33, 7535–7538.
1. Reddy, T. I.; Varma, R. S. Rare-earth (RE) exchanged NaY zeolite promoted Knoevenagel
condenasation. Tetrahedron Lett. 1997, 38, 1721–1724.