Efficient synthesis of chalcone derivatives catalyzed by re-usable hydroxyapatite

Article abstract of DOI:10.1016/j.apcata.2009.12.008

Hydroxyapatite was found to be a very efficient heterogeneous catalyst for the preparation of chalcone derivatives via Claisen-Schmidt condensation using microwave irradiation. The impact of water on the catalyst reactivity was studied and was thought to act as co-catalyst due to the high activation observed in its presence. To investigate the origin of this activation, different organic solvents of similar or higher microwave absorbance as/to water were also tested, and it was confirmed that water is acting as co-catalyst when combined with hydroxyapatite, making the process highly efficient. The catalyst was easily recovered and efficiently re-used.

Full text of DOI:10.1016/j.apcata.2009.12.008

Applied Catalysis A: General 374 (2010) 189–193
Contents lists available at ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Efficient synthesis of chalcone derivatives catalyzed by re-usable hydroxyapatite
b
d
a
e
e
A. Solhy a, , R. Tahir
, S. Sebti , R. Skouta , M. Bousmina , M. Zahouily , M. Larzek
*
b,c,**
a Institute for Nanomaterials & Nanotechnologies (INANOTECH), ENSET, Av. De l’Arme´ Royale, Madinat El Irfane 10100 - Rabat, Morocco
b
´
Laboratoire de Chimie Organique Catalyse et Environnement, Universite´ Hassan II, Faculte´ des Sciences Ben MSik, B.P. 7955, Casablanca, Morocco
c ALS Laboratory Group, Environmental Division, 1313-44 Avenue NE Calgary, AB, Canada T2K 4V8
d Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC Canada H3A 2K6
e
´
´
´
´
Laboratoire de Catalyse, Chimiometrie et Environnement, UFR de Chimie Appliquee, Universite Hassan II-Mohammedia-Casablanca, Faculte des Sciences et Techniques, B.P. 146,
20650 Mohammedia, Morocco
A R T I C L E I N F O
A B S T R A C T
Article history:
Hydroxyapatite was found to be a very efficient heterogeneous catalyst for the preparation of chalcone
derivatives via Claisen–Schmidt condensation using microwave irradiation. The impact of water on the
catalyst reactivity was studied and was thought to act as co-catalyst due to the high activation observed
in its presence. To investigate the origin of this activation, different organic solvents of similar or higher
microwave absorbance as/to water were also tested, and it was confirmed that water is acting as co-
catalyst when combined with hydroxyapatite, making the process highly efficient. The catalyst was
easily recovered and efficiently re-used.
Received 1 October 2009
Received in revised form 3 December 2009
Accepted 3 December 2009
Available online 25 December 2009
Keywords:
Hydroxyapatite
Water
ß 2009 Elsevier B.V. All rights reserved.
Claisen–Schmidt condensation
1. Introduction
considered as one of the greenest solvent and the best alternative
for toxic organic solvents. This will provide various intrinsic
Chalcones form the central core for a variety of important
biological compounds. They show antimalarial [1], anti-inflamma-
tory [2], antileishmanial [3] and anticancer [4] properties. Some
chalcones demonstrated the ability to block the voltage-dependent
potassium channels [5]. They are also known as important
intermediates in the biosynthesis of flavonoids [6] and flavones
[7] which are present in the human diet in soy beans and soy
derived products [8]. The chalcones synthesis via Claisen–Schmidt
condensation was promoted using various homogeneous catalysts.
However, the use of heterogeneous basic catalysts such as alumina
[9], barium hydroxide [10], hydrotalcite [11], zeolite [12], and
natural phosphate [13] were used to facilitate the separation of
obtained pure product. Indeed, the use of heterogeneous catalysts
allows a simplification of the purification step to a simple filtration
and separation of the catalyst from the reaction mixture.
benefits, such as eco-friendlier conditions, the simplification of
protection–deprotection steps, and ultimately the reduction of
waste generation. In addition, the reactions promoted by the use of
microwave irradiation [15] provided many advantages such as
simple, rapid and efficient reactions, decreasing the use of energy
in large scale transformations.
Hydroxyapatite (HAP) has attracted wide attention due to
its use as macroligand for different catalytic active centers.
Indeed, Kaneda and co-workers demonstrated the utility of HAP
as a solid support for Ru, Pd, and La species to perform many
organic transformations [16]. Moreover, Sebti et al. developed a
new family of heterogeneous catalysts based on apatite
structures that can be used directly or after activation by several
methodologies to promote organic reactions [17]. Our group
reported successfully the use of HAP as a solid support in
heterogeneous chemical transformations such as Knoevenagel
reaction [18], Friedel–Crafts alkylation [19] and Michael addition
[20]. In 2002, we published the synthesis of chalcones using
sodium-modified-hydroxyapatite as highly efficient catalyst
[21]. Following our ongoing research on using HAP as catalyst,
herein we wish to report a simple and efficient synthesis
of various chalcones via Claisen–Schmidt condensation using a
re-usable HAP-Water system under microwave irradiation
(Scheme 1).
In the past two decades, there was a tremendous interest in
exploring new chemical reactivity in water [14] which is
* Corresponding author. Fax: +212 537570880.
** Corresponding author at: ALS Laboratory Group, Environmental Division, 1313-
44 Avenue NE Calgary, AB, Canada T2K 4V8. Tel.: +1 403 250 4653;
fax: +1 403 291 0298/+212 522 24 96 72.
E-mail addresses: a.solhy@inanotech.ma (A. Solhy), tahirrachid@yahoo.fr
(R. Tahir).
0926-860X/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.apcata.2009.12.008

190
A. Solhy et al. / Applied Catalysis A: General 374 (2010) 189–193
Scheme 1.
2. Experimental
of the HAP used is represented in Fig. 2. It is characterised by OH
stretching at 3580 cmÀ1,vibrational at 632 cmÀ1and PO4 bands (n3
2.1. Materials and apparatus
1090 cmÀ1and 1041 cmÀ1
,
n
1 963 cmÀ1
,
n
4 600 and 571 cmÀ1, and
n2 472 cmÀ1). There was no evidence of CO3
or any other
2À
All commercial reagents and solvents were used without
further purification. X-ray diffraction (XRD) patterns of the catalyst
were obtained at room temperature on a Bruker AXS D-8
impurities in the powder. The bands corresponding to the n3
vibration of C–O between 1410 and 1470 cmÀ1 and the n2
vibrations between 850 and 890 cmÀ1, characteristic of the
carbonate group, were not observed in the FT-IR spectrum of
HAP confirming the stoichiometric formula of the prepared HAP. In
fact, the basic properties of HAP depend considerably on its
stoichiometry as studied in details by Kibby and Hall [23].
Although, basic sites on non-stoichiometric HAP are less strong
as compared to stoichiometric hydroxyapatite. Moreover, the basic
sites on HAP are assumed to be ÀOH and PO43À. The broad and not
very intense bands at 3450 and 1632 cmÀ1 in HAP are due to the
presence of lattice water in the solid. According to Joris and
Amberg [24], the broadness of the O–H stretching band in the
region 3550–3200 cmÀ1 is due to H-bonding between the
adsorbed H2O and the OHÀ group of the apatite.
diffractometer using Cu K
a radiation in Bragg-Brentano geometry
(
u–2u). The specific surface areas were determined from the
nitrogen adsorption/desorption isotherms at 77 K measured with a
Micromeritics ASAP 2010 automatic analyzer, using the BET
equation. Fourier transform infrared (FT-IR) spectra of samples in
KBr pellets were measured on a Bruker Vector 22 spectrometer.
NMR spectra were recorded on a Bruker ARX 300 spectrometer.
EDS realized by using a FEI Quanta 200 F apparatus.
2.2. Preparation and characterisation of the hydroxyapatite
The synthesis of HAP [Ca10(PO4)6(OH)2] was carried out by the
co-precipitation method [22] (Scheme 2). 250 mL of a solution
containing 7.92 g of diammonium hydrogen phosphate, maintained
at a pH greater than 12, by addition of ammonium hydroxide (BDH)
(60–70 mL), were dropped under constant stirring into 150 mL of a
solution containing 23.6 g of calcium nitrate [Ca(NO3)2.4H2O]. The
suspension was refluxed for 4 h and doubly distilled water (DDW)
was used to prepare the solutions. The HAP crystallites were filtered,
washed with DDW, dried overnight at 80 8C and calcined in air at
900 8C for 30 min before use.
2.3. General procedure for the Claisen–Schmidt condensation
catalyzed by HAP under microwave irradiation
To a solution of aldehyde 1 (2.5 mmol) and acetophenone 2
(2.5 mmol) in MeOH (10 mL) 1 g HAP was added and the mixture
was stirred at room temperature for 5 min. Methanol was
evaporated to give a homogeneous solid. A quantity of water
was added to this solid and the mixture was irradiated by
microwave for the appropriate time at (700 W). CH2Cl2 (2 Â 20 mL)
was added, followed by simple filtration. The solution was
concentrated and purified by re-crystallization. The products were
identified by 1H NMR, 13C NMR, and IR spectroscopy.
Fig. 1. XRD patterns of hydroxyapatite.
3. Results and discussion
The Ca/P ratio obtained by Energy Dispersive X-ray (EDX),
shown in Fig. 1, was as expected for HAP (1.67). The FT-IR spectrum
Scheme 2.
Fig. 2. FT-IR spectrum of HAP.

A. Solhy et al. / Applied Catalysis A: General 374 (2010) 189–193
191
Table 1
Effect of different solvents on HAP reactivity, under microwave irradiation.
Entry
Solvent
Time (min)
Product
Yield (%)
1
2
3
4
5
6
Water
60
60
60
60
60
60
3a
3a
3a
3a
3a
3a
80
30
25
18
45
30
DMF
Butanol
Acetonitrile
Methanol
Ethanol
yield reached 80%. In general, outputs increase at around 0.3 mL of
added water. Beyond this quantity, a notable decrease in yield was
observed. This phenomenon can be explained by the fact that
water would act as co-catalyst at a specific volume, while an
increase in the quantity of water would probably form a water-film
on the active surface of the catalyst affecting its hydrophobicity as
well as the accessibility of the reagents within the pores. To better
understand how water would increase the reactivity of HAP,
different organic solvents of similar or higher microwave absor-
bance to/as water were tested at 0.3 mL. Table 1 summarizes the
results obtained for the synthesis of 3a. The best results were
obtained in presence of water (80%), while moderate yield was
obtained in presence of methanol (45%), molecule sterochemically
similar to water (H replaced by methyl group), and poor yields
were obtained for the other solvents (DMF, butanol, acetonitrile,
and ethanol). With these experiments, it was concluded that water
would rather affect the reactivity of HAP, by acting as co-catalyst,
than just providing an added heat generated by microwave
irradiation to the system.
Fig. 3. Effect of the quantity of water in the synthesis of chalcone 3a (yield after 1 h).
The hydroxyapatite crystallizes in the hexagonal system with
the space group P63/m. The lattice parameters of the prepared HAP
˚
are in excellent agreement with standard data: a = 6.883 A and
˚
c = 9.422 A. While referring to standard data (ASTM) correspond-
ing to the hydroxyapatite, it was noticed that all the peaks
registered in these cards are present.
Surface area of the calcined HAP at 900 8C was determined by
the BET method from the adsorption–desorption isotherm of
nitrogen at its liquid temperature (77 K), and was found to be
S = 15 m2 gÀ1. The total pore volume was calculated by the BJH
method at P/Po = 0.98 (VT = 0.157 cm3 gÀ1).
We were interested to understand the effect of water on the
addition of benzaldehyde and acetophenone catalyzed by HAP
(Fig. 3). In the absence of water, only 20% of the desired product 3a
was obtained in 1 h reaction. The yield was increased significantly
by adding various volume of water. Thus, with 0.3 mL water, the
Afterwards, various chalcones were prepared via the conden-
sation of Claisen–Schmidt, while reacting aryaldehydes on ketones
in the presence of 0.3 mL of water and 1 g catalyst (HAP) under
microwave irradiation (Table 2). In general, good to excellent
yields were obtained.
Table 2
Synthesis of chalcones using HAP as catalyst, under microwave conditions.
Entry
1
Substituents in reagents
Time (min)
Product
Yielda,b (%)
R1
H
R2
H
60
3a
80
2
p-Cl
H
60
3b
88
3
4
m-NO2
p-MeO
H
H
60
90
3c
90
74
3d
5
p-OH
H
120
3e
92

192
A. Solhy et al. / Applied Catalysis A: General 374 (2010) 189–193
Table 2 (Continued )
Entry
Substituents in reagents
Time (min)
90
Product
Yielda,b (%)
R1
H
R2
6
p-MeO
3f
76
7
p-Cl
p-MeO
90
3g
81
8
9
m-NO2
p-MeO
p-MeO
p-MeO
90
3h
3i
70
65
120
10
p-OH
p-MeO
90
3j
79
11
12
H
p-NO2
60
60
3k
86
93
p-Cl
p-NO2
3l
13
14
m-NO2
p-MeO
p-NO2
60
90
3m
3n
89
85
p-NO2
15
p-OH
p-NO2
60
3o
92
a
Isolated yields.
b
Products characterised by 1H NMR, 13C NMR, MS spectroscopy and IR.
A heterogeneous catalyst is more interesting when it can be
product 3a was isolated and identified. A portion of the recovered
catalyst was dried at 150 8C then re-used, and other portion was
washed with acetone and calcined at 900 8C. The results obtained
are represented in Fig. 4. The catalyst calcined at 900 8C, clearly
easily recovered and re-used. For this purpose, the synthesis of 3a
was carried out using fresh and recovered catalyst (HAP) for a 4-
cycle run. After 1 h reaction under microwave irradiation, the

A. Solhy et al. / Applied Catalysis A: General 374 (2010) 189–193
193
Acknowledgement
We are grateful to the Ministry of Higher Education of Morocco
for financial support of this research.
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In summary, we have demonstrated the use of hydroxyapatite–
water system as an efficient and clean catalyst for the preparation
of chalcone derivatives via Claisen–Schmidt condensation under
microwave irradiation. Good to excellent yields were obtained. The
high reactivity of HAP–water coupled with its ease of use and
reduced environmental problems makes it attractive as an
alternative to homogeneous reagents.