Catalysis Communications 4 (2003) 521–524

www.elsevier.com/locate/catcom

Hydroxyapatite: new efficient catalyst for the Michael addition

a,*
M. Zahouily , Y. Abrouki a, B. Bahlaouan a, A. Rayadh a, S. Sebti b

a
Laboratoire de Catalyse, Synthese et Environnement, UFR de Chimie Appliqu ee,
Facult
e des Sciences et Techniques, Universit
e Hassan II, B.P. 146, 20650 Mohammadia, Morocco
b
Laboratoire de Chimie Organique Appliqu ee et Catalyse, Universit
e Hassan II,
Facult
e des Sciences Ben M’Sik, B.P. 7955, 20702 Casablanca, Morocco
Received 16 April 2003; accepted 11 August 2003
Published online: 10 September 2003

Abstract

The synthetic hydroxyapatite is a new basic catalyst for Michael addition of mercaptans to chalcone derivatives with
high yields in few minutes and mild reaction conditions. By-products of usual undesirable reactions in Michael addition
such as 1.2-addition, bis-addition and polymerisation are not observed. The yields obtained are good to excellent.
Ó 2003 Elsevier B.V. All rights reserved.

Keywords: Michael addition; Hydroxyapatite; Heterogeneous catalysis; Recyclable catalyst

1. Introduction [5], aluminium oxide [6], Mg–Al hydrotalcite [7]

Conjugate addition to a; b-unsaturated car-
bonyl compounds is a useful strategy for the
construction of a carbon–carbon and sulfur–
carbon bonds [1–3]. The development of solid
basic catalysts which could replace the liquid bases
currently used in industrial processes is a major
field of to dayÕs catalysis research. In this paper we
report a mild and convenient method for hetero-
geneous catalysis of the Michael addition using
hydroxyapatite (Scheme 1). In heterogeneous
phase various solid catalysts have been found
useful, including zeolite [4], NiBr2 /montmorillonite
*
Corresponding author. Fax: +212-23-31-5353.
E-mail address: m.zahouily@univh2m.ac.ma (M. Zahouily).
and other catalysts with more or less success [8–
11]. Recently, we have shown that natural phos-
phate [12], natural phosphate doped by potassium
fluoride [12], synthetic diphosphate Na2 CaP2 O7
[13] and fluoroapatite [14] are excellent catalysts of
the Michael reaction.
2. Preparation of the catalyst and structural char-
acteristics
The synthesis of the hydroxyapatite (HAP) [15–
19] in powder state is carried out by the co-
precipitation method [20,21] (Scheme 2). Two
hundred and fifty milliliters of a solution contain-
ing 7.93 g of diammonium hydrogen phosphate,
maintained at a pH greater than 12, by addition of

1566-7367/$ - see front matter Ó 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2003.08.001
522 M. Zahouily et al. / Catalysis Communications 4 (2003) 521–524
Scheme 1.
Scheme 2.
ammonium hydroxide (60–70 ml), were dropped
under constant stirring into 150 ml of a solution
containing 23.6 g of calcium nitrate [Ca(NO3 )2

4H2 O]. The suspension was refluxed for 4 h.
Doubly distilled water (DDW) was used to prepare
the solutions. The HAP crystallites were filtered,
washed with DDW, dried overnight at 80 °C and
calcined in air at 700 °C for 30 min before use.
The final product is identified by X-ray dif-
fraction (space group hexagonal system; a ¼ 9:422
 and c ¼ 6:883 A
A ), infrared spectra IR and
chemical analysis. The surface area of calcined
HAP was determined by BET method from
adsorption–desorption isotherm of nitrogen at
its liquid temperature (77 K) and was found to
be S ¼ 38 m2 /g. The total pore volume was cal-
culated by BJH method at P =P0 ¼ 0:98 (Vt ¼ 0:16
cm3 g1 ).
3. Reaction procedure
To a flask containing an equimolar mixture (1
mmol) of thiol 2 and chalcone derivative 1 in
methanol (1.5 ml), HAP (0.1 g) was added and the
mixture was stirred at room temperature until
completion of the reaction, as monitored by thin
layer chromatography (TLC). The reaction mix-
ture was filtered and the catalyst washed with di-
chloromethane. After concentration of the filtrate
under reduced pressure the residue was subjected
to recrystallization (AcOEt/CH2 Cl2 ) or distillation
under vacuum leading to the Michael adduct as
solid. The product structure was analysed by 1 H,
13
C NMR and IR spectrometry.
In all cases the use of HAP as heterogeneous
catalyst in the Michael addition has allowed the
isolation of products 3 rapidly (1–5 min) and with
good to excellent yields (82–96%; Table 1). Except
in the case where the nucleophile is EtCO2 CH2 SH
and Michael acceptor bearing a methyl or meth-
oxy group (entry 15 and 18; Table 1).
4. Results and discussion
Thiophenol and chalcone (X ¼ H, Scheme 1)
were chosen as model substrates to determine
suitable reaction conditions. We proceeded to
study the solvent effect in the synthesis of product
3a using the HAP catalyst. In the cases of hexane,
acetone, butanol, pentanol, iso-propanol no
product was observed. The use of ethanol and
methanol gave after 5 min of reaction, 91% and
93% yield of 3a, respectively. It can be concluded
that ethanol and methanol are the best solvents for
this reaction. A similar effect of solvent has been
observed in the use of the natural phosphate cat-
alyst [12]. In absence of the solvent, only a 5%
yield is obtained. This behaviour indicates that
some solvent is needed to facilitate the contact
between the reagents and active site.
The study of the influence of the volume of the
solvent showed that 0.7–2 ml of methanol per-
mitted to reach the best yield. An increase in the
volume up to 3 ml slightly decreases the reaction
yield (72%), and this drops further to 39% when a
volume of 10 ml is used. The large volume of the
solvent reduces the concentration what explains
the decreasing of the yields. Except in one case, all
 M. Zahouily et al. / Catalysis Communications 4 (2003) 521–524 523

Table 1
Synthesis of products 3 by Michael addition using HAP as catalyst
Yield/% (time/min)a
Entry Products X R HAP
1 3a H –Ph 93 (05)
2 3b ’’ –2–NH2 –C6 H4 96 (03)
3 3c ’’ –CH2 –CO2 Et 82 (05)
4 3d p-Cl –Ph 95 (05)
5 3e ’’ 2–NH2 –C6 H4 – 96 (02)
6 3f ’’ –CH2 –CO2 Et 84 (05)
7 3g m-NO2 –Ph 93 (05)
8 3h ’’ 2–NH2 –C6 H4 – 92 (02)
9 3i ’’ –CH2 –CO2 Et 87 (05)
10 3j p-NO2 –Ph 94 (03)
11 3k ’’ 2–NH2 –C6 H4 – 91 (01)b
12 3l ’’ –CH2 –CO2 Et 91 (05)
13 3m p-OMe –Ph 90 (60)
14 3n ’’ 2–NH2 –C6 H4 – 94 (04)
15 3p ’’ –CH2 –CO2 Et 52 (60)
16 q p-Me –Ph 91 (20)
17 r ’’ 2–NH2 –C6 H4 – 92 (03)
18 s ’’ –CH2 –CO2 Et 68 (60)
a
Yields in pure products isolated by recrystallization with AcOEt/CH2 Cl2 or distillation under vacuum and identified by 1 H, 13
C
NMR and IR spectroscopy.
b
Reaction found 83% of 1.4-addition product and 17% of 1.3-addition product.

the combination lead selectivity to the corre- polarization of the C@O bond and the basic sites
sponding expected 1.4-adducts. No by-products (CaOH and oxygen of PO4 group) enhance the
resulting from the undesirable 1.2-addition and/or thiol nucleophilicity. Consequently, the S–C bond
bis-addition side reactions (usually observed under formation is accelerated and the final product is
classical conditions in some cases) were observed. obtained after protonation of the resulting enolate.
However, reaction of 2-aminothiophenol with The results obtained in this reaction with HAP
Michael acceptor bearing in para position a nitro as catalyst were compared to that of other phos-
group (entry 11 with X ¼ NO2 ) gives a 83/17 phates. Thus the activity of HAP was higher than
mixture of 1.4- and 1.3-addition products. natural phosphate (NP) [12], synthetic diphos-
Solid catalysts become particularly interesting phate Na2 CaP2 O7 [13] and fluoroapatite (FAP)
when they can be regenerated. Indeed, in our case, [14] and slightly lower than potassium fluoride
HAP was recovered quantitatively by simple fil- doped natural phosphate (KF/NP) [12] (Table 2).
tration and regenerated by calcination at 500 °C
during 15 min. The recovered catalysts was reused
several times without loss of activity, even after the Table 2
seventh cycle product 3a was obtained with the Comparison of the activity of HAP with other phosphates
catalysts
same yield.
For the catalytic activity of HAP in this Mi- Yield/% (time/min)
chael addition we speculate that the reaction oc- Catalysts/products 3c 3i
curs at the surface rather than inside tunnels of the HAP 82 (05) 87 (05)
catalyst. The dimension of the tunnels in our cat- FAP [14] 72 (60) 82 (60)
alyst are not large enough compared to those of Na2 CaP2 O7 [13] 56 (45) 63 (40)
zeolites [22]. Thus, we estimate that the surface of NP [12] 56 (45) 86 (20)
KF/NP [12] 95 (05) 97 (05)
HAP to acidic character [23] probably induced the
524 M. Zahouily et al. / Catalysis Communications 4 (2003) 521–524
5. Conclusion
In summary, we have reported a high catalytic
activity and selectivity in Michael reaction of the
HAP catalyst coupled with its ease of use and re-
duced environmental problems. This catalyst can
be regenerated and reused without lost of activity
which make it attractive alternative to homoge-
neous basic reagents.
References
[1] T. Sasai, T. Arai, Y. Satow, K.N. Houk, M. Shibasaki,
J. Am. Chem. Soc. 117 (1995) 6194.
[2] P.H. Lee, H. Ahn, K. Lee, S. Sung, S. Kim, Tetrahedron
Lett. 42 (2001) 37.
[3] S. Cheng, D.D. Cromer, Tetrahedron Lett. 43 (2002) 1179.
[4] R. Sreekurnar, P. Rugmimi, R. Padmakumar, Tetrahedron
Lett. 38 (1997) 6557.
[5] P. Laszlo, P.M-T. Montaufier, S.L. Randriamahefa,
Tetrahedron Lett. 31 (1990) 4867.
[6] U. Sharma, U. Bora, R.C. Boruah, J.S. Sandhu, Tetra-
hedron Lett. 42 (2002) 143.
[7] B.M. Choudary, M. Lakshmi Kantam, Ch. Venkat Reddy,
K. Koteswara Rao, F. Figueras, J. Mol. Catal. 146 (1999)
279.
[8] B.C. Ranu, M. Saha, S. Bhar, Tetrahedron Lett. 34 (1993)
1989.
[9] M. Curini, M.C. Marcotullio, E. Pisani, O. Rosati, Synlett
(1997) 769.
[10] D.J. Macquarrie, Tetrahedron Lett. 39 (1998) 4125.
[11] D.J. Macquarrie, Chem. Commun. 6 (1997) 601.
[12] Y. Abrouki, M. Zahouily, A. Rayadh, B. Bahlaouan,
S. Sebti, Tetrahedron Lett. 43 (2002) 8951.
[13] M. Zahouily, Y. Abrouki, A. Rayadh, Tetrahedron Lett.
43 (2002) 7729.
[14] M. Zahouily, Y. Abrouki, A. Rayadh, S. Sebti, H.
Dhimane, M. David, Tetrahedron Lett. 44 (2003)
2463.
[15] M.E. Fleet, X. Liu, J. Solid State Chem. 149 (2000)
391.
[16] K. Kandori, A. Fudo, T. Ishkawa, Phys. Chem. Chem.
Phys. 2 (2000) 2015.
[17] S. Sugiyama, T. Minamo, T. Moriga, H. Hayashi, K.
Koto, M. Tamka, J.B. Moffat, J. Mater. Chem. 6 (1996)
459.
[18] S. Sugiyama, K. Abe, H. Hayashi, K. Koto, Y. Matsum-
ura, J.B. Moffat, J. Mol. Catal. A 144 (1999) 347.
[19] S. Sebti, R. Tahir, R. Nazih, A. Saber, S. Boulaajaj, Appl.
Catal. A 228 (2002) 155.
[20] T.S.B. Narasaraju, D.E. Phebe, J. Mater. Sci. 31 (1996) 1.
[21] K. Ishikawa, M. Kon, S. Tenshin, N. Kuwayama, Dent.
Mater. J. 9 (1990) 58.
[22] W.F. Holderich, H. Van Bekkum, in: H. Van Bekkum,
E.M. Flanigen, J.C. Jansen (Eds.), Introduction to Zeolite
Science and Practice, Stud. Surf. Sci. Catal., 58, 1991,
p. 631.
[23] S. Sebti, R. Tahir, R. Nazih, S. Boulaajaj, Appl. Catal. A
218 (2001) 25.