Efficient clay supported Ni0 nanoparticles as heterogeneous catalyst for solvent-free synthesis of Hantzsch polyhydroquinoline

Article abstract of DOI:10.1016/j.catcom.2011.12.013

A green and efficient multicomponent one-pot synthesis of Hantzsch polyhydroquinoline was achieved by the condensation of aldehydes, dimedone, ethylacetoacetate and ammonium acetate at room temperature using environmentally benign modified Montmorillonite

Full text of DOI:10.1016/j.catcom.2011.12.013

Catalysis Communications 19 (2012) 1–4
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Efficient clay supported Ni0 nanoparticles as heterogeneous catalyst for solvent-free
synthesis of Hantzsch polyhydroquinoline
⁎
Lakshi Saikia, Dipanka Dutta, Dipak Kumar Dutta
Materials Science Division, CSIR-North East Institute of Science and Technology, Jorhat, 785 006, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 October 2011
Received in revised form 5 December 2011
Accepted 8 December 2011
Available online 16 December 2011
A green and efficient multicomponent one-pot synthesis of Hantzsch polyhydroquinoline was achieved by
the condensation of aldehydes, dimedone, ethylacetoacetate and ammonium acetate at room temperature
using environmentally benign modified Montmorillonite supported Ni0-nanoparticles as catalyst. The well
dispersed Ni0-nanoparticles having a high surface to volume ratio have promising features for the reaction
such as easy removal of the catalyst, solvent-free, shorter reaction time, high product yields (about 95%)
and easy work up procedure. There is no significant effect of electron withdrawing or donating nature of
substituent on aldehydes in the formation of polyhydroquinoline derivatives.
Keywords:
Hantzsch polyhydroquinoline
Dimedone
© 2011 Elsevier B.V. All rights reserved.
Montmorillonite
Ni0-nanoparticles
1. Introduction
be improved by using nanosized catalysts because of their small size
and large surface to volume ratio. It has been observed that Ni0-
4-Substituted 1,4-dihydropyridine (DHP) nucleus comprises a
large family of medicinally important compounds such as Ca2+ chan-
nel blockers and some of the representative compounds of this class
possess acaricidal, insecticidal, bactericidal and herbicidal activities
[1]. 1,4-Dihydropyridine possesses a variety of biological activities,
such as, vasodilator, bronchodilator, anti-atherosclerotic, antitumor,
geroprotective, hepatoprotective and antidiabetic agent [2–5]. Photo-
catalytic oxidation of these compounds to pyridine derivatives consti-
tutes the principal metabolic pathway in biological systems [6].
Therefore, oxidative aromatization of DHPs has been a subject of
great interest of organic and medicinal chemists.
Realizing the importance of polyhydroquinoline derivatives, several
synthesis methods have been reported, like conventional heating [7],
refluxing in acetic acid [8] and microwave irradiation [9] and ultrasound
[10]. Different other approaches for the syntheses of polyhydroquinoline
derivatives using various catalysts, such as TMSCl [11], ionic liquids
[12,13], L-proline [14], polymers [15], Yb(OTf)3 [16], Sc(OTf)3 [17],
HClO4–SiO2 [18], cerric ammonium nitrate [19], heteropoly acid [20],
p-TSA [21], HY-zeolite [22] and Mont. K10 [23] have also been reported
and some of the methods are associated with several shortcomings
such as long reaction times, expensive reagents, harsh reaction condi-
tions, low-product yields and the use of large quantity of volatile organic
solvents.
nanoparticles as catalysts offer great attention for a wide range of appli-
cations in organic transformations such as chemo-selective oxidative
coupling of thiols [24], reduction of aldehydes and ketones [25–27], hy-
drogenation of olefins [28] and support for hydrogen adsorption [29].
Recently, the progress in the field of solvent-free reactions is gaining
significance because of their high efficiency, operational simplicity and
environmentally benign processes. The multi-component reactions
are powerful tools in the modern drug discovery process and allow
fast, automated and high throughput generation of organic compounds.
The possibility of performing multi-component reactions under
solvent-free conditions with a heterogeneous catalyst could enhance
their efficiency from an economic as well as an ecological point of view.
Herein, we would like to report Hantzsch polyhydroquinoline deriv-
ative synthesis catalyzed by modified Montmorillonite supported Ni0-
nanoparticles under solvent-free conditions, using aromatic aldehyde,
dimedone, ethylacetoacetate and ammonium acetate. This method not
only preserves the simplicity, but also consistently gives the corre-
sponding products in good to excellent yields. The modified clay sup-
port has paved the way for better dispersion of the Ni0-nanoparticles
which results in higher catalytic activity.
2. Experimental
In recent years, heterogeneous catalysts are gaining more impor-
tance due to environmental and economic factors. The efficiency can
2.1. Materials and method
Naturally occurring Montmorillonite contains impurities like silica
sand, iron oxide, etc. and were purified by dispersion cum sedimenta-
tion technique [30] to collect the b2 μm fraction. The reagents were
⁎
Corresponding author. Tel.: +91 376 2370 081; fax: +91 376 2370 011.
E-mail address: dipakkrdutta@yahoo.com (D.K. Dutta).
1566-7367/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2011.12.013

2
L. Saikia et al. / Catalysis Communications 19 (2012) 1–4
O
Ar
O
O
COOC H
O
O
2
5
NH OAc/Catalyst
4
RT, No solvent
Ar-CHO
1
+
+
OC H
N
H
2
5
2
3
4
Scheme 1. Modified Montmorillonite supported Ni0-nanoparticle catalyzed synthesis of polyhydroquinone under solvent-free condition.
purchased from Acros Organic, Aldrich, Spectrochem and Merck and
used as received from the supplier without further purification.
catalyst was removed by filtration and washed with dichloromethane
and acetone. Then, the liquid portion was extracted with ethyl acetate
and water to remove any unreacted ammonium acetate; the organic
layer was dried over sodium sulfate and concentrated in vacuum to
afford the crude products. The pure product was obtained by recrystal-
lization from ethanol.
2.2. Preparation of clay supported Ni0-nanoparticles
The preparation of modified Montmorillonite and supported Ni0-
nanoparticles was carried out as reported earlier [31]. In a synthetic
methodology, a known amount of acid treated clay was taken in a
100 ml beaker to which 10 ml (0.05 mM) aqueous solution of Ni
(CH3COO)2 was added under vigorous stirring condition. The stirring
was continued for 5–6 h followed by evaporation to dryness in rotary
evaporator. The dry composite thus obtained was dispersed in 50 ml
ethylene glycol in a double necked round bottom flask and refluxed
for 6 h under nitrogen atmosphere to form an in situ solid product
of Ni0-nanoparticles. The materials were recovered, washed with
methanol until it was free from ethylene glycol and dried at about
40 °C for 12 h. The Ni loading in the supported catalysts was
determined by AAS analysis and found to be 4.85 wt.%.
3. Results and discussion
The XRD patterns of modified Montmorillonite (AT-Mont.) along
with parent clay are shown in Fig. 1. The significant structural modi-
fication of Montmorillonite was reflected in their relative intensity
and location of basal spacing (d001). The parent Montmorillonite
clay exhibited an intense basal peak at 2θ=7.06°, corresponding to
basal spacing of 12.5 Å. When the clay is activated with mineral acid
under controlled conditions for different time periods, the intensity
due to basal spacing (d001) decreases. From the XRD [Fig. 2], the char-
acteristic peaks at 2θ=44°, 51.8° and 76° marked by their indices
(111), (200) and (222) indicate the formation of Ni0 in the nanoparti-
cles. The TEM study [Fig. 3] also reveals the formation of well dispersed
Ni0-nanoparticles of size less than 10 nm on modified Montmorillonite.
The supported Ni0-nanoparticles were investigated as a catalyst in
the synthesis of polyhydroquinoline derivatives i.e. condensation of
benzaldehyde, dimedone, ethylacetoacetate, and ammonium acetate in
the presence of catalytic amount of Ni0-nanoparticles under solvent-
free conditions at room temperature, which afforded product 4a in 95%
yield [Table 1]. Such reaction occurs with a wide range of aromatic alde-
hydes carrying either electron-donating or electron withdrawing sub-
stituents in the ortho, meta, and para positions [Table 1]. The products
were established by comparing their melting points and the spectral
data for selected compounds. A possible explanation for the better
yield in solvent-free conditions is that the eutectic mixture having uni-
form distribution of the reactants brings the reacting species in close
proximity to react than in solvent.
2.3. Characterization
The modified clay support and supported Ni0-nanoparticles were
characterized by using PXRD, surface area analyzer and transmission
electron microscopy (TEM) studies [32]. The powder XRD was recorded
in Rigaku Ultima IV machine with Cu Kα radiation (λ=1.5409 Å).
The textural properties measured by using Autosorb-1 (Quantachome,
USA) and transmission electron microscopy (TEM) image were recorded
on a JEOL JEM-2011 electron microscope.
2.4. Synthesis of Hantzsch polyhydroquinoline derivatives
To a mixture of aromatic aldehyde (1 mmol), dimedone (1 mmol),
ethylacetoacetate (1 mmol), and ammonium acetate (1.5 mmol) in a
10 ml round bottom flask, modified Mont. supported Ni0-nanoparticle
catalyst (25 mg) was added [Scheme 1]. The mixture was homogenized
and stirred at room temperature for 20–25 min, the progress of the re-
action was monitored by thin layered chromatography. After comple-
tion, 10 ml dichloromethane was added to the reaction mixture; the
To investigate the effects of solvent, the condensation reaction of
benzaldehyde, dimedone, ethylacetoacetate, and ammonium acetate
in various organic solvents at room temperature using 4.85 wt.% Ni0-
nanoparticles as the catalyst was carried out. About 75% of the expected
(111)
4000
At-Mont
3500
3000
2500
(200)
2000
Unactivated Mont
(222)
1500
10
20
30
40
40
50
60
70
80
2 Theta (degree)
2 (degree)
Fig. 2. Powder XRD pattern of Ni0-nanoparticles supported on modified Montmorillonite.
Fig. 1. Powder XRD pattern of unactivated and acid treated Montmorillonite (At-Mont.).

L. Saikia et al. / Catalysis Communications 19 (2012) 1–4
3
Fig. 3. Representative TEM image of Ni0-nanoparticles on modified Montmorillonite.
Fig. 4. TEM of Ni0-nanoparticles recovered after run no. 1 of the Hantzsch condensation.
The reusability of supported Ni0-nanoparticles was tested under
similar reaction condition. The catalyst was separated by filtration,
washed, dried and reused for Hantzsch condensation for a fresh reac-
tion mixture up to run no. 4. The results in Fig. 5 showed that there is
a decrease in product yield in subsequent reuse i.e. 95% in run no. 1 de-
creased to 81% in run no. 4. The stability of the used catalyst recovered
after run no. 1 was investigated by HRTEM [Fig. 4] and there is no signif-
icant change in size or shape of the Ni0-nanoparticles. The nanoparticles
were well dispersed on the support and sized in the range of 3–10 nm.
The effect of nickel loading of 1.0, 3.0 and 4.85 wt.% of the catalyst, on
the condensation reaction of benzaldehyde, dimedone, ethylacetoace-
tate, and ammonium acetate was investigated and the corresponding
yields of 41.3%, 69% and 95% were found. This clearly indicates that
4.85 wt.% of Ni nanoparticles showed the best efficacy.
product 4a was obtained when the solvent was ethanol. Obviously, the
polar solvents such as ethanol and acetonitrile [Table 2] were much
better than non polar solvents. It was observed that in the presence of
solvent the reaction takes more time to give high yields of product
under similar ratio of the reactants. This may be due to the competitive
adsorption of the solvent with the substrate molecule on the catalyst
surface; hence reaction under solvent-free condition gives better yields
in less time. The model reaction was carried out without any catalyst,
but the product formation was in poor yield. Therefore, the catalyst
plays an important role in the success of the reaction in terms of rate
and yields of Hantzsch polyhydroquinoline derivatives. The reaction
was also investigated with acid activated Mont. alone as catalyst and
only a negligible amount of product formation was observed. Therefore,
it is evident that supported Ni0-nanoparticles are the active sites.
A comparison of the efficiency of catalytic activity of the modified
Montmorillonite supported Ni0-nanoparticles with several previous
methods is presented in Table 3. The results show that the present
method is better compared to some of the earlier reports in terms
of yield and reaction time.
Table 1
Modified Montmorillonite supported Ni0-nanoparticle catalyzed Hantzsch condensation.
Sr. no.
Ar
Time (min)
Yield %
4a
4b
4c
4d
4e
4f
4g
4h
4i
C6H5
2-Cl.C6H4
4-Cl.C6H4
15
15
15
20
15
20
25
25
20
25
10
95
91
88
87
85
89
82
87
92
86
91
100
80
60
40
20
0
2-NO2.C6H4
3-NO2.C6H4
4-NO2.C6H4
2-OH.C6H4
4-OH.C6H4
4-OMe.C6H4
4-NMe2.C6H4
2,4-Cl.C6H3
4j
4k
Reaction condition: aromatic aldehydes (1 mmol), dimedone (1 mmol), ethylacetoacetate
(1 mmol), ammonium acetate (1.5 mmol) and catalyst — 25 mg, room temperature.
Table 2
Effect of solvent on Hantzsch polyhydroquinoline synthesis.
Solvent
Reaction time (h)
Yield (%)
C2H5OH
CH3CN
Ph–CH3
CH2Cl2
4
4
4
4
75
66
40
37
95
1
2
3
4
No. of Run
No solvent
15 min
Fig. 5. Reusability of supported Ni0-nanoparticles catalyst for the reaction of benzalde-
hyde (1 mmol), dimedone (1 mmol), ethylacetoacetate (1 mmol), ammonium acetate
(1.5 mmol) and catalyst — 25 mg.
Reaction condition: benzaldehyde (1 mmol), dimedone (1 mmol), ethylacetoacetate
(1 mmol), ammonium acetate (1.5 mmol) and catalyst — 25 mg, room temperature.

4
L. Saikia et al. / Catalysis Communications 19 (2012) 1–4
Table 3
Acknowledgments
Comparison of catalytic activity of modified Montmorillonite supported Ni0-nanoparticles
with several known catalysts.
The authors are grateful to Dr. P. G. Rao, Director, North East Institute
of Science and Technology (CSIR), Jorhat, Assam, India, for his kind per-
mission to publish the work. Dr. P. Sengupta, Head, Materials Science
Division is acknowledged for his constant support and encouragement.
Thanks are also due to CSIR, New Delhi for the financial support
(Network Project NWP 0010 and OLP-3700 Non Network Project).
Entry
Condition
Yield (%)
Ref.
1
2
3
4
5
6
Yb(OTf)3, EtOH, rt, 5 h
Sc(OTf)3, EtOH, rt, 4 h
CAN, EtOH, rt, 1 h
90
93
92
93
93
95
[16]
[17]
[19]
[21]
[22]
This work
p-TSA, EtOH, rt, 2 h
HY-Zeolite, CH3CN, rt, 2 h
Modified Mont. supported Ni0-nanoparticles,
solvent-free, 0.25 h
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In conclusion, we have reported that four-component Hantzsch
condensation reaction can effectively be performed with modified
Montmorillonite supported Ni0 nanoparticle catalyst without using
any organic solvent. The yield of Hantzsch polyhydroquinoline deriva-
tives obtained was up to 95% at room temperature. So, the present pro-
cedure provides an efficient and very simple method for the synthesis
of polyhydroquinoline derivatives. The advantage of this method is its
facile conditions and the product can be isolated very easily with excel-
lent purity and that too without the use of column chromatography and
the catalyst is recyclable. The simplicity of the present process makes it
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Compound 4a: 1H NMR (300 MHz, CDCl3) 0.96 (s, 3H), 1.07 (s, 3H),
1.18 (t, 3H), 2.15–2.36 (m, 4H), 2.38 (s, 3H), 4.06 (q, 2H), 5.07
(s, 1H), 5.8 (s, 1H), 7.06–7.34 (m, 5H);
Compound 4e: 1H NMR (300 MHz, CDCl3) 0.94 (s, 3H), 1.08
(s, 3H), 1.21 (t, 3H), 2.11–2.26 (m, 3H), 2.30–2.38 (m, 4H), 3.67
(q, 2H), 5.15 (s, 1H), 6.88 (s, 1H), 7.34 (t, 1H);
Compound 4i: 1H NMR (300 MHz, CDCl3) 0.96 (s, 3H), 1.07 (s, 3H),
1.21 (t, 3H), 2.13–2.28 (m, 3H), 2.34–2.38 (m, 4H), 3.75 (s, 3H),
4.07 (q, 2H), 5.03 (s, 1H), 5.82 (s, 1H), 6.72–6.76 (m, 2H),
7.21–7.24 (m, 2H);
Compound 4j: 1H NMR (300 MHz, CDCl3) 0.97 (s, 3H), 1.08 (s, 3H),
1.23 (t, 3H), 2.10–2.26 (m, 3H), 2.30–2.37 (m, 4H), 2.87 (s, 6H),
4.08 (q, 2H), 4.96 (s, 1H), 5.88 (s, 1H), 6.62 (d, J=8.2 Hz, 2H),
7.16 (d, 2H).
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