Bi-functional modified-phosphate catalyzed the synthesis of α-α′-(EE)-bis(benzylidene)-cycloalkanones: Microwave versus conventional-heating

Article abstract of DOI:10.1016/j.molcata.2010.11.032

The impregnation of hydroxyapatite (HAP) by NaNO₃ leads to a modified-hydroxyapatite which has a bi-functional acid-base property. Sodium-modified-hydroxyapatite (Na-HAP) efficiently catalyzed the cross-aldol condensation of arylaldehydes and cycloketones to afford α-α′- (EE)-bis(benzylidene)-cycloalkanones in good yields under microwave irradiation. Moreover, the methodology described in this paper provides a very easy and efficient synthesis carried out in water as the greenest available solvent under conventional heating. A comparison study between these two different modes of heating was investigated. The catalyst was easily recovered and efficiently re-used.

Full text of DOI:10.1016/j.molcata.2010.11.032

Journal of Molecular Catalysis A: Chemical 336 (2011) 8–15
Contents lists available at ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Bi-functional modified-phosphate catalyzed the synthesis of
␣-␣ꢀ-(EE)-bis(benzylidene)-cycloalkanones: Microwave versus
conventional-heating
Abderrahim Solhya,∗, Walid Amera, Mohamed Karkourib, Rachid Tahirb, Abdeslam El Bouarib,
Aziz Fihrid, Mostapha Bousminaa,c, Mohamed Zahouilya,b,∗∗
a INANOTECH (Institute of Nanomaterials & Nanotechnology), MAScIR Foundation (Moroccan Advanced Science, Innovation and Research), ENSET, Av. De l’Armé Royale, Madinat El
Irfane 10100, Rabat, Morocco
b Laboratoire de Catalyse, Chimiométrie et Environnement (URAC 24), Université Hassan II, Mohammedia B.P. 146, 20650, Morocco
c Hassan II Academy of Science and Technology, Rabat, Morocco
d KAUST Catalysis Center (KCC), King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
The impregnation of hydroxyapatite (HAP) by NaNO3 leads to a modified-hydroxyapatite which has
a bi-functional acid-base property. Sodium-modified-hydroxyapatite (Na-HAP) efficiently catalyzed
the cross-aldol condensation of arylaldehydes and cycloketones to afford ␣-␣ꢀ-(EE)-bis(benzylidene)-
cycloalkanones in good yields under microwave irradiation. Moreover, the methodology described in
this paper provides a very easy and efficient synthesis carried out in water as the greenest available sol-
vent under conventional heating. A comparison study between these two different modes of heating was
investigated. The catalyst was easily recovered and efficiently re-used.
Received 23 June 2010
Received in revised form
13 November 2010
Accepted 27 November 2010
Available online 9 December 2010
Keywords:
© 2010 Elsevier B.V. All rights reserved.
Cross-aldol Condensation
␣-␣ꢀ-(EE)-bis(benzylidene)-cycloalkanones
Hydroxyapatite
Modified hydroxyapatite
Heterogeneous catalysis
Water
Conventional heating
Microwave irradiation
1. Introduction
uniform heating as compared to classical oil or sand bath heating,
resulting in a significant increase of reaction rates even when car-
The use of microwaves has become a well established technique
in chemistry that has found numerous applications in the labora-
tory as well as in industry [1]. It has been successfully used in areas
such as drug discovery, polymer chemistry, material science, nan-
otechnology, and biochemical processes. Moreover, many articles
have been published in the fast-moving field of microwave-assisted
organic syntheses [2], since the appearance of the publication enti-
tled: “The use of Microwave Ovens for Rapid Organic Syntheses”
[3]. The main advantage of microwaves is to provide rapid-and-
ried at the same temperature [4–7]. As a result, microwave-assisted
chemistry has become an important tool in the green chemistry
development [8]. Using microwaves to power chemical reactions
enable chemists to completely eliminate solvents use completely
in some instances. In other cases, water or the eco-friendly solvents
including supercritical CO2, perfluorinated solvents and ionic liq-
uid could replace a variety of organic solvents [9–13]. The use of
water as a medium for organic reactions presents a big challenge
for modern organic chemistry and many reactions that were con-
ventionally believed to occur only in organic solvents have been
found to run in water with excellent conversion [14]. These tech-
niques are completely coherent with the twelve principles of Green
Chemistry, because they meet the advantages of protecting human
health and the environment while simultaneously achieving com-
mercial profitability [15,16]. The development of solid catalysts for
the production of fine chemicals is nowadays a subject of increas-
ing interest [17–20]. Indeed, hydroxyapatite has attracted a wide
∗
Corresponding author. Tel.: +212 537576193; fax: +212 537570880.
Corresponding author at: INANOTECH (Institute of Nanomaterials
∗∗
& Nan-
otechnology), MAScIR Foundation (Moroccan Advanced Science, Innovation and
Research), ENSET, Av. De l’Armé Royale, Madinat El Irfane 10100, Rabat, Morocco.
E-mail addresses: a.solhy@inanotech.mascir.com (A. Solhy),
m.zahouily@inanotech.mascir.com (M. Zahouily).
1381-1169/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2010.11.032

A. Solhy et al. / Journal of Molecular Catalysis A: Chemical 336 (2011) 8–15
9
H
O
O
O
Na-HAP
+
n
A or B
n
R
R
R
1
2
3
A : water / conventional heating
B : without solvent under microwave irradiation
Scheme 1. Cross-aldol condensation over sodium-modified hydroxyapatite.
attention due to its use as inorganic macroligand for solid-base or
acid catalysts [21]. Our research group has demonstrated the cat-
alytic activity of this material, when used alone or modified being
an efficient solid catalyst for many organic transformations [22,23].
The ␣-␣ꢀ-bis(substituted-benzylidene) cycloalkanones are
important pharmacophores and are widely found in many biolog-
ically active compounds such as HIV-1 integrase inhibitory [24],
cytotoxic [25], cancer chemopreventive [26] and have anti-oxidant
properties [27]. Cross-aldol condensation of aromatic aldehydes
with cyclic ketones is an important protocol for the synthesis of
these compounds. This reaction is classically carried out using
strong acid or base [28]. Indeed, different organometallic com-
plexes [29], Lewis acid such as RuCl3 [30], SmI3 [31], BF3 Et2O
[32], FeCl3 6H2O [33], Mg(HSO4)2 [34], Yb(OTf)3 [35], InCl3 4H2O
[36], Cu(OTf)2 [37], and other catalysts such as, SiO2–Pr–SO3H
[38], CH3CO2Na/CH3CO2H under microwave [39], under micellar
medium [40], Polymer-supported sulfonic acid (NKC-9) [41]
SOCl2/EtOH [42], TiCl3(SO3CF3) [43], I2 [44], TMSCl/NaI [45],
LiOH [46], BMPTO [47], and KF/Al2O3 [48] are found to be able
to catalyze this reaction. However, these methods of synthesis
suffer from some drawbacks such as the use of toxic reagents,
unfeasibility of recovering the catalyst, modest yields and long
reaction time. The development of safer, more efficient and
more eco-friendly chemical technologies is a major need for the
humanity in the 21st century. For these reasons and since the last
decade, our research work was focused to develop clean organic
syntheses [22,23,49]. Thus, we present here a new application
of the sodium-modified-hydroxyapatite for the catalysis of the
cross-aldol condensation in water under conventional heating
(Method A) and/or in a solventless system under microwave
irradiation (Method B) (Scheme 1).
6(NH4)2HPO4
10 Ca(NO3)2
8 NH4OH
+
+
Ca10(PO4)6(OH)2
20 NH4(NO3)
6 H2O
+
+
Hydroxyapatite
Scheme 2. Synthesis of hydroxyapatite.
2.2. Catalysts preparation
2.2.1. Preparation of HAP catalyst
The synthesis and characterisation of HAP were already
described [22,23]. The synthesis of HAP [Ca10(PO4)6(OH)2] was
carried out by the co-precipitation method. 250 mL of a solution
containing7.92 gofdiammonium hydrogen phosphate, maintained
at a pH higher 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 fil-
tered, washed with DDW, dried overnight at 80 ◦C and calcined in
an open air at 800 ◦C for 30 min before use (Scheme 2).
2.2.2. Preparation of Na-HAP catalyst
The modified HAP (Na-HAP = 1/2, w/w) was prepared by addi-
tion of HAP (0,1 g) to an aqueous solution of sodium nitrate (50 mL,
1.17 M). The resulting mixture was stirred at room temperature
for 30 min, and then the water was evaporated under vacuum. The
resulting solid was calcined in an open air at 700 ◦C.
2. Experimental
2.1. Materials and apparatus
All commercial reagents were purchased from Aldrich Chem-
ical Company and were used without further purification. X-ray
diffraction (XRD) patterns of the catalyst were obtained at room
temperature on a Bruker AXS D-8 diffractometer using Cu-K˛ radi-
ation in Bragg–Brentano geometry (ꢀ–2ꢀ). The specific surface
areas were determined from the nitrogen adsorption/desorption
isotherms (at −196 C) measured with a Quantachrome Autosorb-1
automatic analyzer, using the BET equation at p/p0 = 0.98. 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. Melting points were
determined using a Stuart SN5228 apparatus. Differential Scanning
Calorimetry (DSC) was conducted under air in a Q100 apparatus.
Elemental analysis (Ca, Na, and P concentrations) was determined
by inductively coupled plasma atomic emission spectroscopy (ICP-
AES) from Jabin Yvan (Ultimate 2).
2.3. General procedure for the synthesis of the
˛-˛ꢀ-(EE)-bis(benzylidene)-cycloalkanones
The typical reaction procedure for the cross-aldol condensation
ofaldehydes with cycloalkanones catalyzed by hydoxyapatite alone
or modified was as follows.
Method A: to a 6 mL of distilled water in a round bottom flask,
was added arylaldehydes 1 (4 mmol), cycloalkones 2 (2 mmol) and
100 mg of the catalyst, and the mixture was refluxed in water.
Method B: to a solution of aldehydes 1 (4 mmol) and cycloalka-
nes 2 (2 mmol), 100 mg of the Na-HAP was added and the mixture
was stirred with a spatula at room temperature and was irradi-
ated by microwave for the appropriate time at (450 W). Hot water
(2 × 20 mL)wasadded, followedbysimplefiltration. For bothmeth-
ods, after filtration and extraction with hot water, the solutions
were concentrated and purified by silica gel chromatography (n-

10
A. Solhy et al. / Journal of Molecular Catalysis A: Chemical 336 (2011) 8–15
Fig. 1. Projection of the hydroxyapatite structure according to the c axis.
hexane/ethyl acetate: 7/3). The products were identified by melting
points, 1H NMR, 13C NMR, and IR spectroscopies. Na-HAP was reac-
tivated by drying at 150 ◦C or, alternatively washed with acetone
and calcined at 600 ◦C for 1 h.
cell along the c axis and form alternate equilateral triangles around
the helicoidal senary axis, their coordination is 7. They are sur-
rounded by six atoms of oxygen [1 O(I), 1 O(II), 4 O(III)] belonging to
[XO4] tetrahedrons and one OH− anion in position 2a (Fig. 3) [51].
The existence of two different calcium sites is of special interest
because the material properties can be tuned by specific modifica-
tion of the site [52]. These channels host OH− groups along the c
axis to balance the positive charge of the matrix. The OH− ions are
located in columns perpendiculars to the unit cell face, at the cen-
tre of the large channels type II. The oxygen of the hydroxyl group
3. Results and discussion
3.1. Catalyst characterization
The preparation of this material was carried out by co-
precipitation method. 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:
˚
is located at 0.4 A out of the plane formed by the calcium ion, and
˚
the hydrogen at 1 A farther, almost on the triangle plane of calcium.
The dimension of the tunnel confers certain mobility to these ions
and allows consequently their circulation along the tunnels in the
direction of OZ axis (Fig. 4). The HAP is a highly non-stoichiometric
calcium phosphate compound with a Ca/P molar ratio ranging from
1.50 to 1.67 [53]. The Ca/P molar ratio of a stoichiometric form of
hydroxyapatite is 1.67. The preparation of the nonstoichiometric
hydroxyapatite can be explained by the fact that the loss of Ca2+
ions and the resulting electrical imbalance are corrected by the
introduction of H+ ions and depletion of OH− ions, denoting this by
the formula Ca10−Z(HPO4)Z(PO4)6−Z(OH)2−Z; 0 < Z ≤ 1 [54]. More-
over, the environment around the OH− sites is very attractive for
substitutions because it allows one to control the ratio between
acid-base sites. It is well known that at a Ca/P ratio of 1.50, HAP
acts as an acid catalyst with the existence always of basic sites. In
contrast, at a Ca/P ratio of 1.67, it acts as a basic catalyst while acid
sites are still present [55]. To sum up, the hydroxyapatite is con-
˚
˚
a = 6.883 A and c = 9.422 A, with all the registered characteristic
peaks of hydroxyapatite being present. The framework of the stoi-
chiometric calcium hydroxyapatite can be described as a compact
assemblage of tetrahedral PO4 groups, where the P5+ ions are in the
centre of the tetrahedrons whose tops are occupied by 4 oxygen
atoms, each PO4 tetrahedron is shared by one column and delimits
two types of unconnected channels (Fig. 1) [50]. The first channel
has a diameter of 2.5 A and is surrounded by Ca2+ ions, denoted CaI
˚
or 4f (4 per unit cell). They are in coordination 9 with the oxygen
atoms of the PO4 tetrahedrons resulting in the formation of a poly-
hedron as shown in Fig. 2. The second type plays an important role
in the properties of the apatites. It has a diameter larger than the
previous one (3–4.5 A), and contains six other Ca2+ ions, referred to
˚
as CaII or 6 h. The latter are located at the periphery of the chan-
nel. These ions are located two dimensions 1/4 and 3/4 of the unit
Fig. 2. Projection showing the arrangement of tetrahedrons [PO4] and the polyhedrons [CaIO9] by giving place to two channels.

A. Solhy et al. / Journal of Molecular Catalysis A: Chemical 336 (2011) 8–15
11
2+
Fig. 3. Projection showing the two channels feature of hydroxyapatite as well as the alternate equilateral triangles formed by CaII having a mixed environment.
Fig. 4. Projection of the structure Ca4(I)Ca6(II)(PO4)6(OH)2 along the b-axis.
NaCaPO4, CaO, and Na2O (Fig. 5). The bulk composition of the HAP
and Na-HAP is summarized in Table 1. Elemental analysis by ICP-
AES (after dissolution in diluted HNO3) indicated that the Ca/P
ratio in HAP corresponded to the theoretical value of stoichiomet-
ric hydroxyapatite (1.67) [55]. The inclusion of sodium affects the
hydroxyapatite structure, and the ratio of Ca/P increases to reach
a value of 2.489, which does not correspond to the hydroxyap-
atite stoichiometric structure. This confirms the observations we
observed by XRD. The percentage of sodium in the analyzed sam-
ple is 9.7%. The specific surface area was determined by the BET
method (S = 1.55 m2 g−1). The TD/DTA analysis of the non-calcined
Na-HAP showed an endothermic behavior at 290–306 ◦C with-
out loss of weight (melting point of NaNO3) and an endothermic
behavior at 600–725 ◦C with 22.5% drop of weight, indicating the
decomposition of NaNO3 (Fig. 6). The basic properties of HAP and
sodium-modified-hydroxyapatite (Na-HAP) have been determined
by the adsorption of phenol (0.6 and 1.6 mmol g−1 in 2 h for HAP
and Na-HAP respectively).
(b)
(a)
10
20
30
40
50
60
70
2θ
Fig. 5. XRD patterns of HAP (a) and Na-HAP (b).
3.2. ˛-˛ꢀ-(EE)-bis(benzylidene)-cycloalkanones synthesis over
Na-HAP under conventional heating and/or microwave irradiation
sidered as a bi-functional catalyst and the control of its acid-base
character depends primarily on the Ca/P molar ratio.
Cross-aldol condensation was first carried out in water using
HAP as a catalyst under conventional heating. In general, the
The basic properties of the HAP have been determined by the
adsorption of phenol which give a value of 0.3 (mmol g−1) for 2 h.
To increase its basic property, HAP was modified by sodium to pro-
vide a catalyst (Na-HAP). Indeed, the value of the adsorbed phenol
on the Na-HAP at the same time (2 h) is 1.6 (mmol g−1). This mod-
ification gives a new strong active catalyst, as it was previously
described [22]. The X-ray diffraction pattern of the calcined Na-
HAP (w/w = 1/2) showed the apparition of new solid phases namely
Table 1
The composition of the catalysts are determined by ICP-AES, and the ratios are
calculated as molar ratios.
Catalyst
Ca/P
(Ca + Na)/P
Na/P
Na (wt%)
HAP
1.67
–
–
–
Na-HAP
2.489
3.009
0.52
2.98

12
A. Solhy et al. / Journal of Molecular Catalysis A: Chemical 336 (2011) 8–15
tional heating. Excellent results (85–96% yields) were obtained and
the reactions were completed after 0.5–2 h (TLC). It can be noticed
that the condensation of various aldehydes with cyclopentanone
is faster than the condensation with cyclohexanone. This may be
due to the removal of the eclipsing effect of adjacent hydrogen
atoms in cyclopentanone after the formation of arylmethylidene
derivative [56]. Moreover, the electron-releasing group (ERG) of
aldehydes (Cl, CH3, OMe), seem to slow down their condensa-
tions with cyclopentanone as will as cyclohexanone (entries 2–4
and 8–10), and that would be because of the decrease in elec-
trophilicity of the active centre of aldehyde. In the case of NO2
which is an electron-withdrawing group (EWG), the same effect
was noted. This may be due to the steric hindrance of this volu-
minous group in meta position. On the other hand, the effect
of conventional heating versus microwave was investigated on
the synthesis of ␣-␣ꢀ-(EE)-bis-(benzylidene)-cycloalkanones. The
cross-aldol condensation of different aldehydes on cycloalkanones
was carried out under microwave irradiation using 10 mol% of cat-
alyst (Na/HAP). Excellent recoveries were obtained (81–97%) in a
relatively short time period (4–10 min). After reaction, the product
is filtered, washed with hot water followed by drying and purifi-
cation. The use of microwave is very helpful to improve the yields
and to decrease the reaction time in comparison to classical thermal
reflux. It was noticed that there was no reaction under microwave
without catalyst, and to what was observed in traditional heat-
ing without solvent. This shows a certain synergy between catalyst
and the microwave. It is thus completely reasonable to think that
the effect of the temperature is a determining factor to promote
this condensation. Unfortunately, domestic microwave was used
and therefore it was impossible to measure the exact temperature
during the reaction. The structures of ␣-␣ꢀ-(EE)-bis-(benzylidene)-
cycloalkanones (3a–3l) were characterized by comparison of their
spectroscopic data (1H NMR and IR) and melting points with those
reported in the literature. The EE geometry of the double bonds
in the above compounds (3a–3l) was based on earlier literature
reports [57]. As noted before, Na-HAP as its homologue HAP is a bi-
functional catalyst which contain at the same time acid and basic
sites. In addition, we believe that the reaction is occurring over both
sites (acid or base) making the catalyst of special interest. More-
over the bi-functional nature (acid/base) of the catalyst as well as
the cooperative effect of the other phases (CaO and Na2O) which
exist with the NaCaPO4 phase contribute significantly to its highly
observed activity. To this end we carried out the reaction of the
synthesis of 3 h under conventional heating in the presence of 0.1 g
of the following catalysts: CaO, Na2O and NaCaPO4. In general, the
obtained yields are poor. Thus, in 3 h reaction, in presence of CaO,
Na2O or NaCaPO4 the yields in product 3 h were 2, 24 and 25%
respectively.
Fig. 6. Sodium nitrate thermogram carried out under nitrogen.
Table 2
Solvent effect on the synthesis of 3a catalyzed by Na-HAP under conventional
heating.
Solvent
n-Butanol
Ethanol
Methanol
Water
Dipole moment, ꢁ (Debye)
Yield (%) in 3a
1.66
30
1.69
40
1.7
70
1.8
96
obtained yields are poor. Thus, in 24 h reaction, the obtained
recoveries in 3a, 3b, 3c, 3d, 3e, 3f, 3 g, 3 h, 3i, 3j, 3k and 3l,
were 25, 30, 27, 25, 30, 35, 24, 35, 25, 20, 28 and 30% respec-
tively. HAP was then activated by sodium nitrate as previously
published. The resulting Na-HAP catalyst used in this study is
prepared according to the method described above. Initially, the
influence of the solvent nature was studied on the synthesis of ␣-
␣ꢀ-(EE)-bis(benzylidene)-cyclopentane 3a under classical heating.
The condensation of cyclopentanone (2 mmol) and benzaldehyde
(4 mmol) (Scheme 1), was carried out in different solvents such as n-
butanol, ethanol, methanol and water (Table 2). The obtained yields
are 30, 40, 70 and 96% respectively. It has been found that water
was the most suitable solvent for the cross-aldol condensation. The
reaction was quite sensitive to the temperature of the solvents, but
especially to the polarity, thus, the yield increases accordingly.
Afterwards, the reaction was carried out in various quantities
of water. In all cases, water seems to positively activate the reac-
tion; however, at higher volume of water the yields start dropping
significantly. The optimum volume of water was determined at
6 mL (Fig. 7). To determine the scope and the limitation of this
reaction, the optimum conditions for the synthesis of the prod-
uct 3a were applied to other substrates. The previous reagents,
reaction time, and product yields for the cross-aldol condensation
are given in Table 3. Different cyclic ketones such as cyclopen-
tanone and cyclohexanone were condensed with various aryl and
heteroaryl aldehydes in water catalyzed by Na-HAP under conven-
Therefore, the proposed reaction mechanism is accordingly
illustrated in Scheme 3. In the first step, the carbonyl group of
cycloalkones 2 is activated by acid site and the proton in position
␣ of carbonyl by the basic site to give a nucleophilic compound on
the level of carbon. This can in turn attack particularly the carbonyl
of the aldehyde which is activated by acid site, making it highly
electrophilic, to give the aldol 4, which then would be dehydrated
to give the product 5. The resulting product would reacts with a
second aldehyde molecule to form ␣,␣ꢀ-bis(substituted benzyli-
dene)cycloalkanone 3. It is though very important to mention that
the catalyst is involved in all these steps by weakening chemical
bonds of the reactants and by consequent lowering the activation
energy.
100
80
60
40
20
0
It is only in theory that the catalyst is found intact at the end
of reaction. All catalysts are exhausted, and when their activities
or selectivities become insufficient, they then have to regener-
ate them under appropriate treatment that will allow them to
recover partially or completely their initial properties. When cycle-
0
2
4
6
8
10
Volume of the water (mL)
Fig. 7. Effect of the volume of water on the synthesis of the product 3a catalyzed by
Na-HAP under conventional heating.

A. Solhy et al. / Journal of Molecular Catalysis A: Chemical 336 (2011) 8–15
13
Table 3
Comparison between conventional heating (method A) and solvent-free microwave methodology (method B), in presence of Na-HAP.
Entry
Cyclo-alkanone
Aldehyde
Productd
Isolated yield (%)a
Method Ab
Method Bc
O
O
O
CHO
1
96 (30)
95 (90)
95 (4)
96 (8)
3a
O
O
O
CHO
2
3
4
Cl
Cl
Cl
3b
O
CHO
91 (90)
90 (60)
97 (10)
96 (10)
H3C
H3C
CH3
3c
O
CHO
MeO
MeO
OMe
3d
O
O
O
O
O
O
CHO
CHO
5
6
96 (30)
92 (90)
95 (6)
92 (8)
3e
O
O2N
NO2
NO2
3f
O
O
O
O
CHO
7
8
9
95 (60)
95 (120)
91 (120)
86 (4)
81 (8)
3g
3h
O
CHO
CHO
Cl
Cl
Cl
O
90 (10)
H3C
CH3
H3C
3i
O
O
CHO
10
85 (120)
92 (10)
MeO
OMe
MeO
3j

14
A. Solhy et al. / Journal of Molecular Catalysis A: Chemical 336 (2011) 8–15
Table 3 (Continued)
Entry
Cyclo-alkanone
Aldehyde
Productd
Isolated yield (%)a
Method Ab
Method Bc
90 (6)
O
O
O
O
O
CHO
11
95 (60)
3k
3l
O
CHO
O
O2N
NO2
12
85 (120)
87 (8)
NO2
a
Values given in parentheses denote the time in minutes.
Reaction carried out in water under conventional heating.
Solvent-free synthesis under microwave irradiation
All products are reported in the literature.
b
c
d
Scheme 3. Proposed mechanism of cross-aldol condensation over sodium-modified-hydroxyapatite.
use (number of regenerations) is bigger, the catalyst becomes more
important. However, it is not sufficient that the catalyst recovers
its activity and selectivity; it must also keep up its stability and
strength in successive regenerations, as well as all its physical and
chemical characteristics. The study of the regeneration and re-use
of Na-HAP was carried out for the microwave-assisted synthesis of
3a. We note that the analysis of the recovered catalyst (Na-HAP)
after second-cycle by ICP-AES shows that the concentrations of the
elements Ca, Na, and P is almost constant compared with base-
line concentrations. Thus, after each cycle, the initial catalyst was
removed, dried and reused in this condensation. The catalyst was
recycled four times, and the activity of the catalyst was found to be
decreasing with each reuse. However, when the recovered catalyst
was washed with acetone and then calcined at 600 ◦C, its catalytic
activity seems to be unchanged for 5-cycle run (Fig. 8). This can
be explained by the fact that after the reaction, a small amount
of reagents remain adsorbed on the dried catalyst, thereby block-
ing accessibility of reagents and molecular traffic. This results in a
decrease of the performance after using this catalyst several times.
But, when we washed and calcined the recovered catalyst, it had its
original activity because this treatment frees the pores which were
blocked and the reagents were made more accessible to the active
sites.
4. Conclusion
In this work, we have developed an efficient and convenient
protocol for the synthesis of ␣-␣ꢀ-(EE)-bis(benzylidene)-
cycloalkanones
via
cross-aldol
condensation
between
arylaldehydes and cycloalkanones catalyzed by sodium-modified-
hydroxyapatite. The reaction can be carried out in water under
classical heating. The microwave-assisted procedure in solvent-
free system has provided a soft and cleaner approach for the
cross-aldol condensation. Compared to conventional heating,
the main advantages of the microwave procedure include mild
conditions, higher yields, shorter reaction period, and catalyst
re-use. Other applications of this method are underway in our
laboratory.
Acknowledgements
Thanks are due to Hassan II Academy of Science and Technol-
ogy and Centre National de la Recherche Scientifique et Technique
(CNRST), for their financial support.
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