Mesoporous nickel hydroxyapatite nanocomposite for microwave-assisted Henry reaction

Article abstract of DOI:10.1016/j.tetlet.2012.03.086

The utility of nickel hydroxyapatite nanocomposite (Ni-HAp) as a green catalyst for solvent free, microwave-assisted Henry reaction using nitromethane and a series of aromatic aldehydes as substrates is presented. The selected catalyst performed well to afford the respective nitrostyrenes which were quantified by gas chromatography equipped with a mass spectral detector (GC-MS). A few of the products were identified from the respective nuclear magnetic resonance (NMR) spectral data.

Full text of DOI:10.1016/j.tetlet.2012.03.086

Tetrahedron Letters 53 (2012) 2980–2984
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Tetrahedron Letters
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Mesoporous nickel hydroxyapatite nanocomposite for microwave-assisted
Henry reaction
N. Neelakandeswari a, G. Sangami a, P. Emayavaramban a, R. Karvembu b, N. Dharmaraj a, , Hak Yong Kim c
⇑
a Department of Chemistry, Bharathiar University, Coimbatore 641 046, India
b Department of Chemistry, National Institute of Technology, Tiruchirappalli 620 015, India
c Inorganic/Organic Nanomaterials Research Laboratory, Department of Textile Engineering, Chonbuk National University, Chonju 561 756, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
The utility of nickel hydroxyapatite nanocomposite (Ni-HAp) as a green catalyst for solvent free, micro-
wave-assisted Henry reaction using nitromethane and a series of aromatic aldehydes as substrates is pre-
sented. The selected catalyst performed well to afford the respective nitrostyrenes which were quantified
by gas chromatography equipped with a mass spectral detector (GC–MS). A few of the products were
identified from the respective nuclear magnetic resonance (NMR) spectral data.
Received 6 November 2011
Revised 21 March 2012
Accepted 22 March 2012
Available online 29 March 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Nickel hydroxyapatite
Green chemistry
Henry reaction
Heterogeneous catalysis
Hydroxyapatite (HAp), Ca10(PO4)6(OH)2 is one of the most
important materials in various fields such as biology, chromatogra-
phy, and catalysis because of its unique property of containing
both acidic and basic sites in a single crystal lattice. HAp has the
potential for both cationic and anionic isomorphous substitutions
leading to a hexagonal unit cell with highly flexible composition.
It has been reported in the literature that the transition metal sup-
ported HAp based solids were more efficient catalysts for the oxi-
dation of alcohols,1 mild racemization of alcohols,2 deprotection of
N-benzyloxycarbonyl group of amino acids,3 Michael addition,4
hydroformylation,5 N-arylation,6 and three component coupling
reactions.7 For a long time, nickel based catalysts have been stud-
ied as one of the best systems for hydrogenation, coupling, dehy-
drogenation, and isomerization reactions and they are more
active at the nanoscale. Nickel catalysts supported on alumina have
been reported to show high activity in catalysis.8
b-Nitrostyrene is an important pharmacophore of many biolog-
ically active molecules with antifungal, antibacterial, and antican-
cer activities. The most commonly practiced protocol for the
synthesis of nitrostyrene and its derivatives involves the coupling
of a nucleophile generated from nitroalkane with the electrophilic
carbon of aldehydes under basic conditions. Classical Henry reac-
tions performed under homogeneous catalytic conditions9,10 suf-
fered from the difficulty to separate the catalyst from the reaction
mixture. Since chemists have long been aware of the ecological
and economical impact of the homogeneous catalytic reactions,
they tried heterogeneous solid catalysts like amberlite, hydrotal-
cites, MgO, layered silicates, etc., for the Henry reaction.11–16
Due to the larger applicability of the products formed in Henry
reaction, methodologies such as sonication or super critical fluids
were applied by some researchers.17 Though these methodologies
are highly explored, their industrial adaptability is hindered by
the facts such as low yield, retro-aldol reaction, side products
formed by the Cannizzaro reaction of aldehydes, requirement of
stoichiometric quantity of base, and purification of products from
the bases. In addition, the nitro alcohol formed should be dehy-
drated using reagents like phthalic anhydride, methane sulfonyl
chloride, dicyclohexylcarbodiimide (DCC), pivaloyl chloride,
ammonium acetate, acetic acid, or amines18 that requires an ele-
vated temperature. Hence, an alternate strategy to overcome the
above mentioned factors was adopted. Microwave-assisted process
is recognized as a versatile method to carry out the large number of
organic reactions that were considered to be difficult with the
involvement of too many steps in the conventional methods.19–22
Microwave approach enhances the merit of the synthesis with
higher yields and the purity of products than the conventional tech-
niques and also satisfies some of the aspects of green chemistry.23
There are several advantages of performing solvent-free synthesis
such as short reaction time, increased safety, and economic advan-
tages of the absence of solvent.24 Hence, we attempted to synthe-
size b-nitrostyrene and its derivatives via microwave-assisted
Henry reaction catalyzed by Ni-HAp. To the best of our knowledge,
this is the first report on the use of Ni-HAp as a heterogeneous cat-
alyst for Henry reaction under microwave irradiation.
⇑
Corresponding author.
E-mail address: dharmaraj@buc.edu.in (N. Dharmaraj).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.086

N. Neelakandeswari et al. / Tetrahedron Letters 53 (2012) 2980–2984
2981
To an equimolar mixture of respective aldehydes and nitro-
methane (0.5 mM), 50 mg of Ni-HAp catalyst was added and irra-
diated in a closed vessel under 160 W microwave radiation for
1 min as given in Scheme 1. Then, the reaction mixture was ex-
tracted with methanol and quantified by GC–MS. The catalyst sep-
arated was washed several times with methanol, dried at room
temperature, and subjected to reusability test.
Gas chromatograph equipped with 5% diphenyl and 95% di-
methyl siloxane, Elite 5MS (60 m length, 0.25 mm dia), and a mass
detector (MS) with helium as a carrier gas was used for the quan-
tification of products. The initial column temperature was in-
creased from 80 to 160 °C at a rate of 10 °C/min and then to
280 °C at the rate of 40 °C/min. The temperatures of the injection
port and transfer line were kept constant at 280 and 250 °C,
respectively, during the product analysis.
The FT-IR spectrum of Ni-HAp presented (Fig. S1) is analogous
to that of the normal apatite structure as evidenced from the liter-
ature. A broad band observed around 3467 cmÀ1 and another weak
band around 1386 cmÀ1 were assigned to the stretching and bend-
ing vibrations of hydroxyl group, respectively. Further, the appear-
ance of three bands at 1023, 614, and 555 cmÀ1 was characteristic
of P–O bonds in (PO4)3À group.25 Loading of Ni onto HAp does not
significantly alter any of these vibrational modes of HAp.
Powder X-ray diffraction pattern of the synthesized Ni-HAp
(Fig. S2) contains peaks corresponding to a mixture of HAp, cal-
cium nickel phosphate (Ca2NiPO4Á2H2O), and NiO. All the diffrac-
tions observed due to Hap and Ca2NiPO4 were indexed based on
the respective JCPDS files (No: 76-0694 and 20-0228). The pres-
ence of hexagonal NiO was also identified from the JCPDS file
(89-7130). These mixed diffraction lines indicated that a part of
Ca2+ ions in the HAp framework was substituted by Ni2+ ions.
Surface morphology and elemental composition of nickel
hydroxyapatite sample were analyzed through SEM equipped with
energy dispersive X-ray analysis. The SEM image of the sample
shown in Figure 1(a) revealed the presence of a flake-like layered
morphology for the prepared Ni-HAp. Further, the presence of
nickel by exchanging calcium ions from HAp was identified from
the elemental composition of EDAX data corresponding to Ca+Ni/
P ratio 1.77 which is very close to the stoichiometry of natural
HAp (Fig. 1b).
A typical TEM image of Ni-HAp with selected area diffraction
pattern and HRTEM image is given in Figure S3, wherein the pres-
ence of flake-like networks with black spots assigned due to hexag-
onal NiO nanoparticles on the surface is observed. The SAED
pattern consists of circular rings rather the individual spots that
confirm the polycrystalline nature of the material as was further
supported by the non-existence of well aligned diffraction lines
in the HRTEM image.
Textural properties of the prepared Ni-HAp sample were inves-
tigated by nitrogen adsorption/desorption analysis. The BET iso-
therm given in Figure S4 is of type-IV in nature.26 The measured
surface area and pore volume of Ni-HAp were found to be
129.6 m2/g and 0.356 cm3/g, respectively, and the pore radius
was found to be nearly uniform that ranges between 5 and 8 nm.
It is noteworthy to mention here that a very narrow distribution
of pore size was obtained in the absence of any template or other
super critical conditions.
Figure 1. (a) SEM image and (b) EDAX spectrum of Ni-HAp.
Table 1
Catalyst quantity optimization using benzaldehyde and nitromethane
S. No
Catalyst quantity (mg)
Yield (%)
1
2
3
4
0
25
50
75
0
65.4
95.6
96.1
In the temperature programed reduction profile (Fig. S5), a
reduction peak was observed at 740 °C corresponding to the reduc-
tion of Ni2+ incorporated into the Ca(I) sites of the apatite.25 Fur-
ther, the amount of hydrogen consumed for reduction was found
to be 0.167 mM/g which corresponds to the reduction of
0.334 mM of Ni2+ per gram of Ni-HAp.
The oxidation state of the constituent metal ions as well as the
environment around the active sites of Ni-HAp catalyst surface was
investigated through XPS. The XPS plot of Ni-HAp is given in Figure
S6. A detailed scan of the Ni 2p core level reveals its binding energy
around 854.3 eV corresponding to NiO.27 The shake-up satellite
peak registered at 859.6 eV, characteristic of Ni2+ species, con-
firmed the presence of Ni2+ as NiO. A little higher binding energy
value corresponding to Ni2+ obtained in our case than the free/
unsupported NiO (853.5 eV) suggested a strong interaction be-
tween the metal ion and the support.28
O
NO2
Ni-HAp
H
+
CH3NO2
Microwave
R
R
Optimization of reaction conditions
R= Cl, Br, –OCH3, –NO2 or –N(CH3)2.
In order to optimize the more suitable reaction conditions for
the preparation of nitrostyrene and its derivatives via this novel
Scheme 1. Microwave assisted Henry reaction.

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N. Neelakandeswari et al. / Tetrahedron Letters 53 (2012) 2980–2984
Table 2
Microwave-assisted Henry reaction of nitromethane with various aldehydes
S. No.
1
Substrate
Product
Yielda (%)
95.6
O
NO2
H
O
NO2
NO2
H
H
2
3
96.2
96.5
Cl
Cl
Br
O
Br
NO2
O
NO2
NO2
4
5
63.9
69.3
H
O
O2N
O2N
NO2
O2N
H
H
O
NO2
6
97.1
O2N
O
NO2
OCH3
H
7
8
9
47.2
NR
OCH3
O
NO2
H
OH
OH
O
NO2
NO2
H
NR
OH
OH
O
H
10
69.8
N
N
N
S
H
11
12
58.0
62.5
N
S
NO2
NO2
O
H
O
O
NO2
H
13
47.5
O
O
O
NO2
14
15
76.2b
74.9b
N
Cl
N
Cl
O
H3CO
NO2
H3CO
N
Cl
N
Cl

N. Neelakandeswari et al. / Tetrahedron Letters 53 (2012) 2980–2984
2983
Table 2 (continued)
S. No.
Substrate
Product
Yielda (%)
O
NO2
16
75.6b
N
Cl
N
Cl
NR- No reaction.
a
GC yield = (peak area of the product/total peak area) Â 100.
b
Isolated yield.
conducted but without the catalyst wherein the reaction did not
proceed at all.
Table 3
Results of reusability test using benzaldehyde and nitromethane as substrates
The generality of the reaction was studied by extending it to
nitromethane and a series of aromatic aldehydes and the result is
presented in Table 2. From the data of Table 2, it is clear that aro-
matic aldehydes bearing electron withdrawing substituents were
more reactive toward Henry reaction than those with electron
donating groups as reported earlier for the same reaction catalyzed
by layered silicates.15 However, salicylaldehyde and 2-hydrox-
ynaphthaldehyde (Table 2, entries 8 and 9) did not undergo con-
densation with nitromethane under the optimized reaction
conditions. The non-reactivity of them has been attributed to the
preferred deprotonation of –OH group of salicylaldehyde or naph-
thaldehyde on the catalyst surface resulting in the formation of
electron rich carbon center at the carbonyl group.
S. No
Catalytic cycle
Yield (%)
1
2
3
4
Cycle 1
Cycle 2
Cycle 3
Cycle 4
95.6
94.9
94.2
93.1
green chemical approach, quantity of the catalyst required was
determined by choosing benzaldehyde and nitromethane as model
substrates. A linear relationship was observed between the quan-
tity of nitrostyrene formed and the amount of catalyst used as pre-
sented in Table 1 with 50 mg of the catalyst as a limiting case.
Further increase in the quantity of catalyst did not show apprecia-
ble improvement in the yield of nitrostyrene. To ascertain the role
of Ni-HAp for the Henry reaction, a similar experiment was
Similar reactions carried out with hydrotalcite catalyst under
conventional reaction conditions yielded only 8% of the corre-
sponding nitroaldol even after 5 h of the reaction time.18 Though
NO2
O
H
z
+
CH3NO2
R
R
H
H
C
R
H
H
H
R
C
NO2
NO2
O
H
O
H
H
z
z
H
H
H
H
R
R
H
C
NO2
C
H
NO2
H
O
O
H
z
z
Step III
Figure 2. Mechanism for Henry reaction on Ni-HAp surface.

2984
N. Neelakandeswari et al. / Tetrahedron Letters 53 (2012) 2980–2984
the yield of nitro-olefin from the reactions of heterocyclic alde-
hydes like pyridine-2-carboxaldehyde and thiophene-2-carboxal-
dehyde (Table 2, entries 11 and 12) was moderate, they are quite
satisfactory upon comparison with the base catalyzed Henry reac-
tions under microwave conditions.18 Presence of substituents at a
position ortho to the carbonyl group decreased the yield of nitro-
styrenes considerably due to steric reasons. Though Henry reaction
is already reported under microwave conditions, this is the first re-
port on the condensation of formyl-quinoline or its derivatives
with nitromethane to afford a satisfactory yield of nitro-vinyl quin-
olines (Table 2, entries 14–16). The structure of respective quino-
line derivatives was confirmed from their spectral data. A band
appeared around 760 cmÀ1 in the FT-IR spectra of entries 14–16
in Table 2, confirmed the presence of C–Cl bond in their structure.
Further, the formation of conjugated olefinic system in nitrosty-
renes was identified from the corresponding NMR data. These
observations proved the specificity of the catalyst toward the
polarizable carbonyl group but not the labile functional groups like
–Cl, –Br, –NO2, etc., Since Ni-HAp catalyst possess both acidic and
basic sites on the surface, it has the capability to hold both car-
bonyl group of aldehydes as well as the active methylene carbon
of nitromethane in close proximity and thus favored the formation
of cyclic intermediate followed by dehydration to the desired
nitrostyrene.
transition state rather than the ground state and hence increases
the reaction rate.
Acknowledgment
The authors sincerely thank Professor K. Pitchumani, Senior
Professor in Chemistry, the Madurai Kamaraj University, Madurai,
India, for useful scientific discussions related to this work. We are
grateful to the Department of Science and Technology (DST), Min-
istry of science and Technology, Government of India, New Delhi
for the financial support to this work. (DST Project file No. SR/S1/
IC-45/2007 dated 02.04.2008).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.03.
086.
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