A mild route for one pot synthesis of 5,6-unsubstituted 1,4-dihydropyridines catalyzed by sulphated mixed metal oxides

Article abstract of DOI:10.1039/c3cy00651d

Synthesis of 1,4-dihydropyridines via a four component one pot reaction starting from α,β-unsaturated aldehyde, β-keto ester, amine and alcohol, catalysed by SO₄^2-/Ce_xZr _1-xO₂ is explored. The method has several advantages such as reusability of catalyst, avoidance of a multistep procedure and readily available starting materials. The protocol gives high to moderate yields for structurally diverse amines, β-keto esters and α,β-unsaturated aldehydes. SO₄^2-/Ce_xZr_1-xO ₂ (x = 0.02-0.15 mol%) catalysts were prepared and characterized by various analytical techniques such as XRD, FT-IR, TGA-DSC, SEM-EDAX and the total acidity.

Full text of DOI:10.1039/c3cy00651d

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A mild route for one pot synthesis of 5,6-unsubstituted
1,4-dihydropyridines catalyzed by sulphated mixed
metal oxides†
Cite this: Catal. Sci. Technol., 2014,
4, 672
a
a
b
a
*
*
Sandeep S. Kahandal, Sandip R. Kale, Manoj B. Gawande and Radha V. Jayaram
Synthesis of 1,4-dihydropyridines via a four component one pot reaction starting from α,β-unsaturated
aldehyde, β-keto ester, amine and alcohol, catalysed by SO42−/CexZr1−xO2 is explored. The method has
several advantages such as reusability of catalyst, avoidance of a multistep procedure and readily available
starting materials. The protocol gives high to moderate yields for structurally diverse amines, β-keto esters
and α,β-unsaturated aldehydes. SO42−/CexZr1−xO2 (x = 0.02–0.15 mol%) catalysts were prepared and char-
acterized by various analytical techniques such as XRD, FT-IR, TGA-DSC, SEM-EDAX and the total acidity.
Received 30th August 2013,
Accepted 12th November 2013
DOI: 10.1039/c3cy00651d
www.rsc.org/catalysis
2,6-dimethyl-4-substituted-1,4-dihydropyridines and 5,6-unsubstituted
1,4-dihydropyridines.10 Among them, the development of
Introduction
Dihydropyridines and their derivatives are important
analogues of NADH coenzymes that could be involved in
hydrogen transfer reactions.1 A literature study reveals that
1,4-dihydropyridines (1,4-DHPs) exhibit neuroprotectant and
platelet anti-aggregratory activity and also shows biological
properties such as being cerebral anti-ischemic agents in the
treatment of Alzheimer's disease, being effective calcium
channel modulators for the treatment of cardio-vascular dis-
orders, dimeric 4-aryl-1,4-dihydropyridines as a third class of
nonpeptide HIV-1 protease inhibitor and as chemosensitizers
in tumour therapy.2–5 1,4-DHPs constitute a molecular frame-
work able to provide ligands for diverse receptors6 and also
exhibit diverse biological and pharmological applications;7
they have proven to be important synthetic intermediates,
including in the synthesis of nitrogen containing alkaloids.8
The most common method for the synthesis of symmetrical
1,4-DHPs is the Hantzsch synthesis route based on the reaction
of β-keto ester, ammonium salt and aldehyde, but many of
those methodologies suffer from drawbacks such as longer
reaction time, harsh reaction conditions, and lower yield of
products.9 Additionally, the Hantzsch synthesis and related
methods are not applicable for the synthesis of some important
unsymmetrical derivatives such as N-aryl-1,4-dihydropyridines,
efficient methods for the synthesis of 5,6-unsubstituted
1,4-dihydropyridines is particularly important for systematic
study of their biological activities and this type of substitution
pattern allows the use of dihydropyridines as nucleophiles11 or
the dienophile component in acid-catalyzed imino Diels–Alder
reactions,12 and they can also be used as enamine-like reagents
for the preparation of a variety of complex heterocyclic com-
pounds.13 To the best of our knowledge, very few methods are
available for the synthesis of unsymmetrical 5,6-unsubstituted
1,4-dihydropyridines, such as use of piperidine, ceric ammo-
nium nitrate–neutral alumina, Mg(ClO4)2, p-toluenesulphonic
acid, InCl3, chiral phosphonic acid, nano CuO, LiI and FeCl3.
But they are also restricted to the synthesis of the less reactive
N-aryl derivatives, give mixtures of products, require harsh reac-
tion conditions, β-enaminoesters and β-enaminoketones as
starting materials, inert atmosphere, dehydrating agent and
longer reaction times and lead to formation of pyridinium salts
as side products.14
Environmental and economic considerations have recently
given rise to strong attention to the redesigning of commer-
cially important processes so that the use of harmful sub-
stances and the generation of toxic waste can be avoided.15
In this respect, heterogeneous catalytic processes are more
favourable over their homogeneous counterparts in the pro-
duction of chemicals, owing to their ease of handling, simple
workup procedures and, most importantly, their reusability.16
Sulphated metal and mixed metal oxides gained much more
recognition than metal and mixed metal oxides due to their
higher number of acid sites and larger surface area, which
resulted in enhanced catalytic activity.17
a Department of Chemistry, Institute of Chemical Technology, Matunga,
Mumbai 400 019, India. E-mail: rv.jayaram@ictmumbai.edu.in;
Fax: +91 22 3361 1020; Tel: + 91 22 3361 1111/2222
b Regional Centre of Advanced Technologies and Materials, Faculty of Science,
Department of Physical Chemistry, Palacky University, Šlechtitelů 11, 783 71,
Olomouc, Czech Republic. E-mail: manoj.gawande@upol.cz,
mbgawande@yahoo.co.in; Tel: +420 585 634 385
Sulphated ceria–zirconia as a solid acid catalyst has been suc-
cessfully used for 2-propanol dehydration, cumene dealkylation,18
† Electronic supplementary information (ESI) available: Experimental details
and characterization data of selected products. See DOI: 10.1039/c3cy00651d
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and modified Ritter reaction.19 In continuation of our efforts
in nanocatalysis, green synthesis and application of heteroge-
neous catalysts in various organic transformations,20–22 we
herein report a mild, green and simple catalytic protocol that
uses inexpensive and reusable catalysts for the one pot synthe-
sis of 5,6-unsubstituted 1,4-dihydropyridines catalyzed by
sulphated mixed metal oxides.
In this paper, we have explore surface modified metal oxides
and mixed metal oxides as catalysts for a four component
reaction of amine, α,β-unsaturated aldehyde, β-keto ester and
alcohol (Scheme 1). Reusability of the catalysts, avoidance of
multiple steps and readily available starting materials makes
this synthetic route more attractive and environmentally benign.
Fig. 1 XRD patterns of (a) ZrO2, (b) CeO2, (c) SO42−/ZrO2,
(d) SO42−/Ce0.02Zr0.98O2, (e) SO42−/Ce0.07Zr0.93O2, (f) SO42−/Ce0.10Zr0.90O2
and (g) SO42−/Ce0.15Zr0.85O2.
Results and discussion
X-Ray diffraction analysis
The XRD patterns of sulphated metal oxides and mixed metal
oxides with different Ce content are shown in Fig. 1. All the
samples were crystalline in nature, wherein CeO2 forms a solid
solution with ZrO2. SO42−/CexZr1−xO2 (x = 0.02–0.15 mol%)
show characteristic peaks of catalytically active tetragonal
phase (2θ = 30.18° (with 100 as relative intensity) and the peaks
located at 34.616°, 35.283°, 50.214°, 50.770°, 59.291°, 60.187°,
62.724° and 74.617°) [d–g]. The oxide of cerium (CeO2) shows
characteristic peaks of fluorite phase, whereas ZrO2 is present
in both tetragonal and monoclinic phases [a–b]. Sulphated
zirconia shows characteristic peaks of tetragonal phase, which
is supposed to be the catalytically active phase [c].
FT-IR spectral analysis
Fig. 2 FT-IR spectrum of (a) CeO2, (b) ZrO2, (c) SO42−/CeO2, (d) SO42−/ZrO2,
(e) SO42−/Ce0.02Zr0.98O2, (f) SO42−/Ce0.07Zr0.93O2, (g) SO42−/Ce0.10Zr0.90O2
and (h) SO42−/Ce0.15Zr0.85O2.
FT-IR spectra were recorded to confirm the presence of
sulphate ion units on the surface of ceria–zirconia (Fig. 2).
The intense absorption bands at around 1250, 1222, 1142
and 1096 cm−1 are assigned to the S–O stretching frequency
region for bidentate sulphate ions coordinated to the metal.
The former and the latter two bands are assigned to asym-
metric and symmetric stretching vibrations of the OSO
and O–S–O groups, respectively. The bands at 1625 cm−1 and
1635 cm−1 are assigned to the deformation vibration modes
of the adsorbed water (e–h). These characteristic bands of
bidentate sulphate ions are absent in unsulphated ZrO2 and
CeO2 (a–b). In sulphated zirconia, IR absorption bands were
observed in the same region as those of the SO42−/CexZr1−xO2 (d).
In sulphated ceria, slight shift of absorption bands at 1300,
1143, 1196 and 1056 cm−1 was observed (c).
Potentiometric titration for determination of total acidity
The determination of the total acid sites of the catalysts
was carried out by a potentiometric titration method, in which
the total number of acid sites was determined by using
n-butylamine in acetonitrile as a non-aqueous medium.
In this method, the initial electrode potential (Ei) indicates
the strength of the acid sites and the end point of the titration
expressed in mmol g−1 indicates the total number of acidic
sites.23 The results indicate a good correlation with product
yield, strength (Ei) and number of acid sites (Table 1). The
highest amount of n-butylamine consumed was 4.23 mmol g−1
for the SO42−/Ce0.07Zr0.93O2, as compared to other catalysts
used in the present study (Fig. 3).
TGA-DSC profile of the catalysts
The thermal stability of SO42−/CexZr1−xO2 (x = 0.2–0.15) cata-
lysts was investigated by TGA-DSC thermal analysis. The first
Scheme 1 SO42−/CexZr1−xO2 catalysed four component reaction of
amine, α,β-unsaturated aldehyde, β-keto ester and alcohol.
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Table 1 Effect of catalysts on the synthesis of 5,6-unsubstituted 1,4-dihydropyridinesa
Entry
Catalyst
Total acidityb (mmol g−1
)
Eic (mV)
Yieldd (%)
1e
2e
3e
4
5
6
7
8
9
10
11
12
13
14
15
16f
—
CeO2
—
0.3
0.8
—
27
14
17
48
25
77
76
94
70
50
43
51
57
80
65
60
47
ZrO2
55
154
168
440
560
450
460
148
195
310
530
330
248
—
SO42−/CeO2
1.22
2.07
3.17
4.23
3.52
3.50
1.23
1.64
1.93
4.19
2.91
2.65
—
SO42−/ZrO2
SO42−/Ce0.02Zr0.98O2
SO42−/Ce0.07Zr0.93O2
SO42−/Ce0.10Zr0.90O2
SO42−/Ce0.15Zr0.85O2
SO42−/Y0.04Zr0.96O2
SO42−/Y0.08Zr0.92O2
SO42−/Y0.12Zr0.88O2
SO42−/Y0.16Zr0.84O2
SO42−/Y0.20Zr0.80O2
SO42−/Y0.24Zr0.76O2
SO42−/CeO2 + SO42−/ZrO2
a
Reaction conditions: ethyl acetoacetate (2 mmol), n-butylamine (2 mmol), cinnamaldehyde (2.2 mmol) ethanol (2 mmol), acetonitrile (4 ml),
1.5 h, 32 °C (RT), catalyst: 20 wt% w.r.t. to β-keto ester. b Total acidity values determined by n-butylamine potentiometric titration method. c Ei – initial
electrode potential (mV). d Isolated yield. e 5 h. f 10 (wt%) of each catalyst with respect to β-keto ester.
Fig. 3 Potentiometric titration curves for (a) , SO42−/Ce0.07Zr0.93O2;
(b) , SO42−/Ce0.02Zr0.98O2; (c) , SO42−/Ce0.10Zr0.90O2; (d) , SO42−/CeO2;
(e) , CeO2; (f) , ZrO2; (g) , SO42−/ZrO2; (h) , SO42−/Ce0.15Zr0.85O2.
Fig. 4 DSC-TGA curves of (a) SO42−/Ce0.02Zr0.98O2, (b) SO42−/Ce0.07 Zr0.93 O2,
(c) SO42−/Ce0.10Zr0.90O2 and (d) SO42−/Ce0.15Zr0.85O2.
weight loss for all the compositions occurs below 200 °C,
which is due to the loss of physically adsorbed water. The
catalysts exhibit good thermal stability and no further
remarkable weight loss was observed up to 700 °C. The next
prominent weight loss of the catalysts occurs at 700 °C to
800 °C mainly due to decomposition of sulphate species
with the evolution of SO3 (a–d). The endothermic peaks at
712–728 °C observed in the case of SO42−/CexZr1−xO2 (x = 0.2–0.15)
samples are due to the evolution of SO3 from sulphate species
bonded to the surface of sulphated ceria–zirconia. The decom-
position temperature depends on the amount of Ce and sul-
phate species present in the catalyst. The decomposition
temperature increases (713–728 °C) with increasing Ce con-
tent from 0.02–0.15 mol%, resulting in increased thermal
stability of the surface sulphate species (Fig. 4).
micrograph of the sample is shows in Fig. 5a. EDX-XAF analy-
sis showed 7 mol% of Ce and 93.0 mol% of Zr metal in the
case of SO42−/Ce0.07Zr0.93O2. The results are in good agreement
with the calculations and minimal difference was observed
(Fig. 5b). The EDAX spectrum of sulphated ceria–zirconia
clearly indicated the presence of Ce and Zr metals (Fig. 5b).
Catalytic studies
In general, the unsymmetrical dihydropyridines are synthe-
sized by conducting a reaction between ethyl acetoacetate
(1a), n-butylamine (2a) and cinnamaldehyde (3a) with ethanol
to primarily form the alkoxy derivatives of dihydropyridines
(Scheme 2, 6a). These alkoxy derivatives will be further
treated with an acid catalyst such as neutral Al2O3 in acetoni-
trile under reflux conditions to form the final desired product
dihydropyridine (7a). In this method, the synthesis of substituted
dihydropyridine and unsubstituted dihydropyridine require
different catalysts and reaction conditions.24 However we
SEM-EDAX analysis of SO42−/Ce0.07Zr0.93O2
SEM-EDAX analysis was performed using a tungsten source
on JEOL model JSM-6390 instrument. The scanning electron
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intermediate (β-enaminone), which upon further addition of
the cinnamaldehyde (3a) with ethanol in the same pot and
the same reaction conditions for 1 h, gives the desired dihydro-
pyridine (7a) in good yield. It should also be noted that without
the addition of ethanol, which results in a prior substitution at
the 6-position of the ring, the reaction did not take place under
experimental conditions.
Encouraging preliminary results prompted us to test the
model reaction with various metal oxides and mixed metal
oxides and their surface modified forms (Table 1, entries 1–16).
In the absence of catalyst, only 14% product yield was
observed, even after a prolonged reaction time (Table 1,
entry 1). The yield of the desired products was much lower
when the reaction was carried out in the presence of CeO2
or ZrO2 alone, (Table 1, entries 2–3) as compared to those
obtained with their sulphated forms (Table 1, entries 4–5).
It is well documented that when mixed metal oxides are
sulphated their acidity improves to a large extent, thus
improving their catalytic activity. The investigation was initi-
ated on several compositions of sulphated ceria–zirconia
and sulphated yttria–zirconia catalysts, and it was observed
that sulphated ceria–zirconia provides superior catalytic
activity as compared to the sulphated yttria–zirconia for
the synthesis of 5,6-unsubstituted 1,4-dihydropyridines
(Table 1, entries 6–15). Total acidity and surface area of
SO42−/CexZr1−xO2 increased as the content of cerium increased
from 0.02–0.07 mol% but further increase of cerium content
resulted in the decrease of total acidity and surface area
(see ESI†). This trend correlates well with the observed cata-
lytic activity.
Fig. 5 (a) SEM image and (b) EDAX spectrum of SO42−/Ce0.07Zr0.93O2.
The SO42−/Ce0.07Zr0.93O2 catalyst gave 94% yield of the
product, which is highest amongst the several compositions
of SO42−/CexZr1−xO2 and SO42−/YxZr1−xO2 catalysts studied in
the present investigation (Table 1, entry 7). A physical mix-
ture of SO42−/CeO2 and SO42−/ZrO2 (10 wt% of each) gave
47% yield of the desired product (Table 1, entry 16). The
highest catalytic activity of SO42−/Ce0.07Zr0.93O2 catalyst
could be attributed to the surface area (53 m2 g−1) and acidity
(4.23 mmol g−1). The initial electrode potential (Ei) of 560 mV
also indicates the presence of very strong acid sites. The total
number of acid sites and their strength was determined by
potentiometric titration using n-butylamine. In this method
the initial electrode potential (Ei) indicates the strength of
the acid sites and the end point of the titration expressed in
mmol g−1 indicates the total number of acidic sites.
In acid catalysed reactions the amount of catalyst
employed is one of the important factors and hence efforts
were made to determine the optimum loading of catalyst
required. The model reaction was carried out in the presence
of SO42−/Ce0.07Zr0.93O2 at various catalyst loadings (Table 2,
entries 1–6), and it was found that an increase of the catalyst
loading from 5 to 20 wt% resulted in an increase in the yield
of dihydropyridine up to 94% (Table 2, entries 1–4). The yield
of the reaction remained unchanged beyond 20 wt% of the
catalyst (Table 2, entries 5–6). Hence, 20 wt% of catalyst load-
ing was selected for further investigations.
Scheme 2 Mechanistic rationale proposed for the four component
one pot reaction for the synthesis of dihydropyridine compounds.
could formulate a synthetic methodology in which the same
catalyst system could couple both of these reaction steps in
one pot (Scheme 1). To this effect, the reported synthesis is
both cost and energy efficient.
In any sequential reaction, the initial step plays an important
role as the complexity of the subsequent steps can be reduced
to a large extent if the desired product is selectively obtained in
the first step. In order to optimize the reaction conditions for
the synthesis of 5,6-unsubstituted 1,4-dihydropyridines, reaction
of ethyl acetoacetate, n-butylamine, cinammaldehyde and etha-
nol was carried out as model reaction. Ethyl acetoacetate (1a)
and n-butylamine (2a) are treated for 30 min at 32 °C (room
temp.) by using SO42−/CexZr1−xO2 catalysts. This forms an
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Table 2 Effect of catalyst loading on the synthesis of 1,4-dihydropyridinesa
Table 4 Effect of various substituents on the synthesis of 5,6-unsubstituted
1,4-dihydropyridinesa
Entry
Catalyst loading (wt%)
Yieldb (%)
Entry
Product
R1
R2
R3
Yield (%)b
1
2
3
4
5
6
5
10
15
20
25
30
75
82
87
94
95
95
1
7a
7a
7b
7c
7d
7e
7e
7f
7g
7h
7i
7j
7k
7l
n-Butyl
n-Butyl
n-Methyl
n-Allyl
n-Hexyl
Ph
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OMe
OMe
OMe
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
Me
Me
Me
Me
Me
Me
Me
Ph
94
92
83
72
79
76
78
84
80
78
88
90
85
78
76
73
72
74
2c
3
4
5
6
a
7c
8
Ph
Reaction conditions: ethyl acetoacetate (2 mmol), n-butylamine
(2 mmol), cinnamaldehyde (2.2 mmol), ethanol (2 mmol), acetonitrile
(4 mL), 1.5 h, 32 °C (rt), SO42−/Ce0.07Zr0.93O2 catalyst: wt.% w.r.t. ethyl
acetoacetate. b Isolated yield.
PhCH2
4-Cl-Ph
n-Butyl
n-Butyl
n-Allyl
n-Hexyl
n-Heptyl
PhCH2
n-Heptyl
PhCH2
n-Heptyl
9
10
11
12
13
14
15
16
17
18
The effect of solvent on the reaction was also studied
(Table 3, entries 1–10). Under solvent-free conditions only
35% yield of desired product was obtained (Table 3, entry 1).
When the reaction was carried out in 1,4-dioxane, diethyl
ether and chloroform solvents, low yield of product was
obtained (Table 3, entries 2–4). Ethyl acetate and tetrahydro-
furan gave moderate yields of 7a (Table 3, entries 5–6). It
was observed that in dichloromethane, dichloroethane and
acetone the reaction proceeded more rapidly, but better
results were obtained with acetonitrile solvent (Table 3,
entries 7–10). It is clearly indicates that using polar solvents
as the reaction medium gave better yields as compared to
non-polar solvents for the synthesis of dihydropyridines.
Applicability of the reaction protocol to various structur-
ally diverse amines, β-keto esters and α,β-unsaturated alde-
hyde with ethanol was also tested (Table 4, entries 1–18). The
model reaction of ethyl acetoacetate (1a), n-butylamine (2a)
and cinnamaldehyde (3a) gave 94% yield of the desired
dihydropyridine (Table 4, entry 1). Structurally diverse amines
with ethyl acetoacetate (1a), cinnamaldehyde (3a) and ethanol
(Table 4, entries 3–6, 8–9) gave good yields of dihydropyridines
(72–84%, 7b–7g). When cinnamaldehyde was replaced with
acrolein, 78% yield of the desired product was obtained
(Table 4, entry 10, 7h). The synthetic protocol was also found
7m
7n
7o
7p
a
Reaction condition: β-keto ester (2 mmol), amine (2 mmol),
α,β-unsaturated aldehyde (2.2 mmol), ethanol (2 mmol), acetonitrile
(4 ml), 1.5 h, 32 °C (RT), SO42−/Ce0.07Zr0.93O2 catalyst : 20 wt% w.r.t
b
c
to β-keto ester. Isolated yield. β-Keto ester (15 mmol), amine
(15 mmol), α,β-unsaturated aldehyde (16.5 mmol), ethanol (15 mmol),
acetonitrile (30 ml).
to be compatible with several structurally diverse amines with
crotonaldehyde (but-2-enal) providing good yields (76–90%,
7i–7m) of the desired dihydropyridines (Table 4, entries 11–15).
When the protocol was extended to heptylamine and benzylamine
with replacement of ethyl acetoacetate by methyl acetoacetate,
good yield of the desired products was obtained (Table 4,
entries 16–18, 7n–7p). In order to evaluate the possibility of
increasing the scale of application of our methodology, we
carried out the synthesis of dihydropyridine from 15 mmol of
starting materials without any noticeable loss in catalytic
activity (Table 4, entries 2, 7). Thus, aromatic, aliphatic and
acid sensitive amines, β-keto-esters and α,β-unsaturated alde-
hydes were found to be viable for these transformation to give
high to moderate yields under mild reaction conditions.
On the basis of experimental results and a literature
survey, a possible reaction mechanism for the synthesis of
dihydropyridine involves the formation of a β-enaminones as
an intermediate in the initial step. The second step involves
Michael addition of an α,β-unsaturated aldehyde (3a) to the
β-enaminone to form hydroxytetrahydropyridine 5a, which
is finally transformed into the 6-alkoxy derivative of tetra-
hydropyridine 6a.25 In the final step, ethanol is eliminated
from 6a to give the desired product 7a (Scheme 2).
Table 3 Effect of solvent on the synthesis of 5,6-unsubstituted
1,4-dihydropyridinesa
Entry
Solvent
Yield (%)b
1c
2
3
4
5
6
7
8
9
—
35
49
54
60
65
67
80
83
85
94
1,4-Dioxane
Diethyl ether
Chloroform
Ethyl acetate
Tetrahydrofuran
Dichloromethane
Dichloroethane
Acetone
A standard leaching experiment for the model reaction
with SO42−/Ce0.07Zr0.93O2 was carried out. The model reaction
proceeded for 50 min at 32 °C, the reaction mixture and cata-
lyst were then separated under suction. The reaction mixture
was then stirred for the appropriate time, but no enhancement
in the yield was observed. This result clearly shows that the reac-
tion proceeded heterogeneously and no homogeneous catalyst
10
Acetonitrile
a
Reaction conditions: ethyl acetoacetate (2 mmol), n-butylamine
(2 mmol), cinnamaldehyde (2.2 mmol) ethanol (2 mmol), solvent
(4 ml), 1.5 h, 32 °C (rt), catalyst : 20 wt% w.r.t. to β-keto ester.
b
Isolated yield. c No solvent.
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FT-IR, TGA-DSC, SEM–EDAX and total acidity determined
using n-butylamine by potentiometric titration method. The
percentage conversion, purity and relative yields of the final
products were determined by using a Thermofisher GC-1000
equipped with a capillary column (30 m × 0.32 mm ID-0.25 μm
BP-10) with an FID detector and high purity nitrogen as the car-
rier gas. The products were identified by GC-MS by using a
Shimadzu (GCMS-QP 2010) E.I. mode with high purity helium as
carrier gas. Powder XRD patterns of catalysts were recorded on a
Bruker AXS diffractometer D8 Cu-Kα radiation (λ = 1.540562)
over a 2θ range of 0–80°. SEM-EDAX was recorded using a
tungsten source on a JEOL model JSM-6390 instrument. Ther-
mograms were recorded on a SDT Q 600v 8.2 Build 100 model
by TA instruments. Potentiometric titrations were carried out
by using Equip-tronic model (EQ-614A) instruments with a
double junction electrode. For analytical and thin-layer chro-
matography, Merck, 0.2 mm and 0.5 mm Kieselgel G F 254
precoated were used, respectively.
Fig. 6 Test for catalyst leaching a) reaction with catalyst for 90 min.
b) Reaction in the filtrate, after 50 min of reaction with catalyst.
Table 5 Recyclability of the catalystsa
Run
1
2
3
4
5
Yieldb (%)
94
93
93
91
90
Catalyst preparation
a
Reaction conditions: ethyl acetoacetate (2 mmol), n-butylamine
(2 mmol), cinammaldehyde (2.2 mmol), ethanol (2 mmol), acetonitrile
(4 mL), 1.5 h, 32 °C (r.t.), catalyst: 20 wt% w.r.t. to ethyl acetoacetate.
The SO42−/CexZr1−xO2 were prepared by the method described
by Lee et al.25 Precipitation of Zr(OH)4 was obtained by
adding aqueous ammonia into a 0.25 M solution of zirconium
oxychloride at room temperature with vigorous stirring until
the pH of the mother liquor reached at 8. The preparation of
catalyst doped with Ce and modified with sulphate simulta-
neously was carried out by adding an acidic aqueous solution
of cerium sulphate (Ce(SO4)2·4H2O) to the Zr(OH)4 followed
by drying at 110 °C for 24 h and calcined at 650 °C for 2 h.
The series of catalysts was prepared by varying the mol% of
cerium (0.02–0.15) added to the catalyst.
b
Isolated yield.
was involved while performing the reaction (Fig. 6,a–b). The
reusability of the sulphated ceria–zirconia was tested for the
synthesis of 1,4-dihydropyridines. At the end of the reaction, the
heterogeneous catalyst was separated by simple filtration and
the recovered catalyst again used for next cycle after washing
with acetone and drying in an oven at 110 °C for 2 h. It was
observed that the catalyst retained its catalytic activity for dihydro-
pyridine synthesis even after the fifth catalytic cycle (Table 5).
Catalyst characterization
After calcination, sulphated ceria–zirconia was characterized
by XRD, FT-IR, TGA-DSC, SEM-EDAX and total acidity deter-
mined by the n-butylamine potentiometric titration method.
Powder X-ray diffraction (XRD) patterns were obtained using
Bruker AXS diffractometer D8 Cu-Kα radiation (λ = 1.540562)
over a 2θ range of 0–80°. SEM-EDAX analysis was performed
using a tungsten source on JEOL model JSM-6390 instru-
ment. Thermogravimetric analysis under a nitrogen atmo-
sphere was carried out using SDT Q 600v 8.2 Build 100 model
by TA instruments. Potentiometric titrations were carried out
by using Equiptronic model (EQ-614A) instruments with a
double junction electrode. The Fourier transform infrared
spectra (FT-IR) of the samples were recorded on a FT-IR spec-
trometer (Spectrum 100) Perkin-Elmer by the KBr method.
Conclusions
In conclusion, we have demonstrated a simple and efficient
procedure for the one pot synthesis of 5,6-unsubstituted 1,4-
dihydropyridines using surface modified metal oxides and
mixed metal oxides. The advantageous like operational sim-
plicity, mild reaction conditions, high yields and reusability
of the catalysts make this protocol an important addition to
the existing methods of dihydropyridine synthesis. This proto-
col is applicable for structurally diverse amines, β-keto-esters
and α,β-unsaturated aldehydes provides good yields. The
catalyst is reusable up to five consecutive cycles without any
prominent loss of catalytic activity. Sulphated ceria–zirconia
exhibits superior catalytic activity over the sulphated yttria–
zirconia catalysts.
A typical experimental procedure for the synthesis
of dihydropyridines
Experimental
General information
A 10 mL round-bottomed flask was charged with suitable
amine (2 mmol) and β-keto ester (2 mmol), SO42−/Ce0.07Zr0.93O2
(20 wt%) along with acetonitrile (4 mL) and the solution was
stirred at room temperature for 30 minutes. To this solution
was then added an α,β-unsaturated aldehyde (2.2 mmol) with
All the chemicals and catalysts were purchased from firms of
repute with their highest purity available and were used as
provided. Sulphated ceria–zirconia was characterized by XRD,
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ethanol (2 mmol). The reaction mixture was further stirred at
room temperature for 1 h, the catalyst was separated by sim-
ple filtration and the filtrate dried over anhydrous Na2SO4
and concentrated to dryness. The progress of the reaction was
monitored by TLC and GC. All the products obtained and
discussed in this work have been previously reported and rep-
resentative products were characterized by suitable technique
169.7. GC–MS (EI, 70 eV): m/z (%) = 265 [M+] (14%), 250
(100%), 234 (6%), 218 (15%), 206 (10%), 120 (20%), 106 (35%).
Acknowledgements
S. S. Kahandal is thankful to Council of Scientific and Indus-
trial Research (CSIR) New Delhi, India for providing a Senior
Research Fellowship (09/019(0072) 2009-EMR-I). The author
gratefully acknowledges the support by the Operational Pro-
gram Research and Development for Innovations – European
Regional Development Fund (project CZ.1.05/2.1.00/03.0058)
and by the Operational Program Education for competitive-
ness – European Social Fund (project CZ.1.07/2.3.00/30.0041)
of the Ministry of Education, Youth and Sports of the
Czech Republic.
1
such as H NMR (Varian 300 MHz) and GC-MS (Shimadzu QP
2010) analysis.
A typical experimental procedure for the scale up of
the procedure
A 25 mL round-bottomed flask was charged with amine
(15 mmol) and β-keto ester (15 mmol), SO42−/Ce0.07Zr0.93O2
(20 wt%) and acetonitrile (30 mL) and the solution was
stirred at room temperature for 30 minutes. To this solution
was then added an α,β-unsaturated aldehyde (16.5 mmol)
with ethanol (15 mmol). The reaction mixture was further
stirred at room temperature for 1 h, the catalyst was sepa-
rated by simple filtration and the filtrate dried over anhy-
drous Na2SO4 and concentrated to dryness. The progress of
the reaction was monitored by TLC and GC.
References
1 (a) R. J. Lavilla, J. Chem. Soc., Perkin Trans. 1, 2002, 1141;
(b) A. Sausins and G. Duburs, Heterocycles, 1988, 27, 269.
2 M. Kawase, A. Shah, H. Gaveriya, N. Motohashi,
H. Sakagami, A. Varga and J. Molnar, Bioorg. Med. Chem.,
2002, 10, 1051.
3 (a) R. A. Janis, P. J. Silver and D. J. Triggle, Adv. Drug Res.,
1987, 16, 309; (b) F. Bossert and W. Vater, Med. Res. Rev.,
1989, 9, 291.
Characterization data of some selected compounds
1-Butyl-2-methyl-4-phenyl-1,4-dihydropyridine-3-carboxylic
acid ethyl ester (Table 4, entry 1). Light yellow viscous liquid.
1H NMR (300 MHz, CDCl3, 25 °C, ppm): δ = 0.99 (t, 3H), 1.13
(t, J = 7.1 Hz, 3H), 1.31–1.46 (m, 2H), 1.55–1.68 (m, 2H), 2.49
(s, 3H), 3.21–3.32 (m, 1H), 3.44–3.56 (m, 1H), 3.99 (q, J = 7.1 Hz,
2H), 4.60 (d, J = 5.6 Hz, 1H), 4.96 (dd, J = 5.6, 7.5 Hz, 1H), 5.91
(d, J = 7.6 Hz, 1H), 7.15–7.55 (m, 5H). 13C NMR (75 MHz,
CDCl3, 25 °C, ppm): δ = 14.3, 14.7, 16.2, 20.1, 32.7, 40.5, 50.4,
59.5, 99.9, 108.2, 126.3, 127.7 (2C), 128.6 (2C), 129.3, 149.1,
149.7, 169.6. GC–MS (EI, 70 eV): m/z (%) = 299 [M+] (24%),
270 (15%), 254 (10%), 226 (50%), 222 (100%), 194 (20%),
166 (9%), 138 (30%), 57 (8%), 41 (14%).
1-Butyl-2-methyl-1,4-dihydropyridine-3-carboxylic acid ethyl
ester (Table 4, entry 10). 1H NMR (300 MHz, CDCl3, 25 °C, ppm):
δ = 0.92 (t, J = 7.2 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H), 1.29–1.38
(m, 2H), 1.44–1.56 (m, 2H), 2.31 (s, 3H), 3.1 (d, J = 3.5 Hz, 2H),
3.2 (t, J = 7.2 Hz, 2H), 4.05–4.13 (m, 2H), 4.68–4.75 (m, 1H),
5.67 (d, J = 7.9 Hz, 1H). 13C NMR (75 MHz, CDCl3, 25 °C,
ppm): δ = 14.3, 14.9, 15.8, 20.3, 24.9, 32.7, 50.2, 59.6, 94.9,
104.2, 130.9, 150.9, 169.6. GC–MS (EI, 70 eV): m/z (%) = 223
[M+], (62%) 194 (27%), 178 (20%), 150 (100%), 134 (58%), 106
(55%), 91 (60%).
4 A. Zarghi, H. Sadeghi, A. Fassihi, M. Faizi and A. Shafiee,
Il Farmaco, 2003, 58, 1077.
5 A. Hilgeroth, Mini-Rev. Med. Chem., 2002, 2, 235.
6 (a) G. Muller, Drug Discovery Today, 2003, 8, 681; (b)
R. W. DeSimone, K. S. Currie, S. A. Mitchell, J. W. Darrow
and D. A. Pippin, Comb. Chem. High Throughput Screening,
2004, 7, 473; (c) A. A. Shelat and R. Kiplin Guy, Nat. Chem.
Biol., 2007, 3, 442; (d) B. E. Evans, K. E. Rittle, M. G. Bock,
R. M. DiPardo, R. M. Freidinger, W. L. Whitter, G. F. Lundell,
D. F. Verber, P. S. Anderson, R. S. L. Chang, V. J. Lotti,
D. H. Cerino, T. B. Chen, P. J. Kling, K. A. Kunkel,
J. P. Springer and J. Hirshfield, J. Med. Chem., 1998, 31, 2235.
7 (a) D. J. Triggle, Cell. Mol. Neurobiol., 2003, 23, 293; (b)
K. Ohashi and A. Ebihara, Cardiovasc. Drug Rev., 2007, 14, 1;
(c) B. J. Epstein, K. Vogel and B. F. Palmer, Drugs, 2007, 67,
1309; (d) R. H. Fagard, J. Clin. Basic Cardiol., 1999, 2, 163; (e)
M. D. Vergouwen, M. Vermulen, R. J. De Haan, M. Levi and
Y. B. Roos, J. Cereb. Blood Flow Metab., 2007, 27, 1293; (f)
T. Straub, C. Boesenberg, V. Gekeler and F. Boege,
Biochemistry, 1997, 36, 10777; (g) I. O. Donkor, X. Zhou,
J. Schmidt, K. C. Agrawal and V. Kishore, Bioorg. Med.
Chem., 1998, 6, 563; (h) A. Kuzmin, S. Semenova,
N. F. Ramsey, E. E. Zvartau and J. M. Van Ree, Eur. J.
Pharmacol., 1996, 295, 19; (i) E. Teodori, S. Dei, S. Scapecchi
and F. Gualtieri, Farmaco, 2002, 57, 385; (j) C. Advendano,
J. C. Menéndez Curr. Med. Chem., 2002, 9, 159; (k) J. Robert
and C. Jarry, J. Med. Chem., 2003, 46, 4805; (l) C. Avendano
and J. C. Menendez, Med. Chem. Rev.–Online, 2004, 1, 419;
(m) A. Hilgeroth, Mini-Rev. Med. Chem., 2002, 2, 235; (n)
A. Hilgeroth and H. Lilie, Eur. J. Med. Chem., 2003, 38, 495;
1-Heptyl-2,4-dimethyl-1,4-dihydropyridine-3-carboxylic acid
1
methyl ester (Table 4, entry 16). Colorless viscous liquid. H
NMR (300 MHz, CDCl3, 25 °C, ppm): δ = 0.85–0.89 (m, 3H),
0.93 (d, J = 6.4 Hz, 3H), 1.28–1.57 (m, 10H), 2.36 (s, 3H),
3.09–3.19 (m, 1H), 3.28–3.48 (m, 2H), 3.65 (s, 3H), 4.85 (dd,
J = 6.1, 7.3 Hz, 1H), 5.79 (d, J = 7.4 Hz, 1H). 13C NMR
(75 MHz, CDCl3, 25 °C, ppm): δ = 14.0, 15.6, 22.5, 24.8, 26.5,
28.1, 28.9, 30.3, 31.7, 50.1, 50.5, 100.3, 108.9, 129.2, 149.1,
678 | Catal. Sci. Technol., 2014, 4, 672–680
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Paper
(o) A. S. Misra1, S. Ganesh, A. Shahiwala and S. P. Shah,
J. Pharm. Sci., 2003, 6, 252; (p) N. Bodor and P. Buchwald,
Drug Discovery Today, 2002, 7, 766; (q) L. Prokai, K. Prokai-
Tatrai and N. Bodor, Med. Res. Rev., 2000, 20, 367.
L. Sambri, Synlett, 2007, 18, 2897; (d) D. D. Weller and
H. Rapoport, J. Am. Chem. Soc., 1976, 98(21), 6650; (e)
M. L. Kantam, T. Ramani, L. Chakrapani and B. M. Choudary,
Catal. Commun., 2009, 10, 370; (f) P. T. Franke, R. L. Johansen,
S. Bertelsen and K. A. Jørgensen, Chem.–Asian J., 2008, 3,
216–224; (g) J. Jiang, J. Yu, X. X. Sun, Q. Q. Rao and L. Z. Gong,
Angew. Chem., Int. Ed., 2008, 47, 2458; (h) R. K. Vohra,
C. Bruneau and J.-L. Renaud, Adv. Synth. Catal., 2006, 348,
2571; (i) J. K. F. Geirsson and J. F. Johannesdottir, J. Org.
Chem., 1996, 61, 7320; (j) A. J. Kay, A. D. Woolhouse,
G. J. Gainsford, T. G. Haskell, T. H. Barnes, I. T. McKinnie and
C. P. Wyss, J. Mater. Chem., 2001, 11, 996; (k) S. Maiti and
J. C. Menéndez, Synlett, 2009, 14, 2249.
8 (a) D. M. Stout and A. I. Meyers, Chem. Rev., 1982, 82, 223;
(b) D. L. Comins and S. O'Connor, Adv. Heterocycl. Chem.,
1988, 44, 199; (c) K. Achiwa and T. Kato, Curr. Org. Chem.,
1999, 3, 77; (d) R. Kumar and R. Chandra, Adv. Heterocycl.
Chem., 2001, 78, 269; (e) R. J. Lavilla, J. Chem. Soc., Perkin
Trans. 1, 2002, 1141; (f) D. S. Johnson and J. J. Li, The Art of
Drug Synthesis, John Wiley and Sons, New York, 2007, ch. 11.
9 (a) G. D. Henry, Tetrahedron, 2004, 60, 6043; (b) F. Lieby-
Muller, C. Allias, T. Constantieux and J. Rodriguez, Chem.
Commun., 2008, 4207; (c) C. Simon, T. Constantieux and
J. Rodriguez, Eur. J. Org. Chem., 2004, 4957.
10 (a) N. M. Evdokimov, I. V. Magedov, A. S. Kireev and
A. Kornienko, Org. Lett., 2006, 6, 899; (b) V. Sridharan,
P. T. Perumal and C. Avendan, J. C. Menéndez Tetrahedron,
2007, 63, 4407; (c) G. Bartoli, K. Babiuch, M. Bosco,
A. Carlone, P. Galzerano, P. Melchiorre and L. Sambri,
Synlett, 2007, 2897; (d) L. Singh, M. P. S. Ishar, M. Elango,
V. Subramanian, V. Gupta and V. P. Kanwal, J. Org. Chem.,
2008, 73, 2224; (e) M. Li, Z. Zuo, L. Wen and S. Wang,
J. Comb. Chem., 2008, 10, 436; (f) P. T. Franke,
R. L. Johansen, S. Bertelsen and K. A. Jørgensen, Chem.–
Asian J., 2008, 3, 216; (g) A. Kumar and R. A. Maurya,
Tetrahedron, 2008, 64, 3477; (h) I. Carranco, J. L. Díaz,
O. Jiménez and R. Lavilla, Tetrahedron Lett., 2003, 44, 8449;
(i) R. Lavilla, M. C. Bernabeu, I. Carranco and J. L. Díaz,
Org. Lett., 2003, 5, 717; (j) R. Lavilla, I. Carranco, J. L. Díaz
and M. C. Bernabeu, Mol. Diversity, 2003, 6, 171; (k) O. Jiménez,
G. de la Rosa and R. Lavilla, Angew. Chem., Int. Ed., 2005, 44,
6521; (l) C. Masdeu, E. Gomez, N. A. O. Williams and R. Lavilla,
Angew. Chem., Int. Ed., 2007, 46, 3043; (m) X. Q. Zhu, B. J. Zhao
and J. P. Cheng, J. Org. Chem., 2000, 65, 8158; (n) X. Q. Zhu,
H. Y. Wang, H. Y. Wang, J. S. Wang and Y. C. Liu, J. Org. Chem.,
2001, 66, 344; (o) M. Kidwai and R. Mohan, Can. J. Chem.,
2004, 82, 427; (p) D. Shi, D. Shi, C. Yu, C.-X. Yu, Q.-Y. Zhuang
and Q.-Y. Zhuang, J. Chem. Res., 2008, 8, 441; (q) H. Jiang,
R. Mai, H. Cao, Q. Zhu and X. Liu, Org. Biomol. Chem., 2009,
7, 4943; (r) A. T. Khan and M. M. Khan, Tetrahedron Lett.,
2011, 52, 3455.
15 (a) J. Chen, S. K. Spear, J. G. Huddleston and R. D. Rogers,
Green Chem., 2005, 7, 64; (b) H. Zeng, Q. Tian and H. Shao,
Green Chem. Lett. Rev., 2011, 4(3), 281–287; (c) A. Taguchi
and F. Schüth, Microporous Mesoporous Mater., 2005, 77(1),
1–45.
16 (a) J. Beckers and G. Rothenberg, Green Chem., 2010, 12,
939; (b) F. Rajabi, S. Ghiassian and M. R. Saidi, Green Chem.,
2010, 12, 1349; (c) S. Yan, M. Kim, S. O. Salley and
K. Y. Simon Ng, Appl. Catal., A, 2009, 60, 363.
17 (a) A. Keshavaraja, V. R. Hegde, B. Pandey, A. V. Ramaswamy,
P. Kumar and T. Ravindranathan, Angew. Chem., Int. Ed.
Engl., 1995, 34, 2143; (b) K. V. Katkar, P. S. Chaudhari and
K. G. Akamanchi, Green Chem., 2011, 13, 835; (c) Z. Si,
D. Weng, X. Wu, J. Yang and B. Wang, Catal. Commun., 2010,
11, 1045; (d) D. E. Lopez, J. G. Goodwin Jr, D. A. Bruce and
S. Furuta, Appl. Catal., A, 2008, 339, 76; (e) M. L. Testa,
V. L. Parola, L. F. Liotta and A. M. Venezia, J. Mol. Catal. A:
Chem., 2013, 367, 69.
18 J. R. Sohn, S. H. Lee and J. S. Lim., Catal. Today, 2006,
116, 143.
19 (a) S. S. Kahandal, S. R. Kale, S. T. Disale and R. V. Jayaram,
Chem. Lett., 2012, 41, 738; (b) S. S. Kahandal, S. R. Kale,
S. T. Disale and R. V. Jayaram, Synfacts, 2012, 8(10), 1161; (c)
S. S. Kahandal, S. R. Kale, S. T. Disale and R. V. Jayaram,
J. Cheminf., 2012, 49, 43.
20 (a) M. B. Gawande, P. S. Branco and R. S. Varma, Chem. Soc.
Rev., 2013, 42, 3371; (b) M. B. Gawande, A. Rathi, I. D. Nogueira,
C. A. A. Ghumman, N. Bundaleski, O. M. N. D. Teodoro and
P. S. Branco, ChemPlusChem, 2012, 77, 865; (c) M. B. Gawande,
P. S. Branco, I. D. Nogueira, C. A. A. Ghumman, N. Bundaleski,
A. Santos, O. M. N. D. Teodoro and R. Luque, Green Chem.,
2013, 15, 682; (d) M. B. Gawande, D. B. Bonifacio Vasco,
R. Luque, P. S. Branco and R. S. Varma, Chem. Soc. Rev.,
2013, 42, 5522; (e) M. B. Gawande, A. Rathi, I. D. Nogueira,
R. S. Varma and P. S. Branco, Green Chem., 2013, 15, 1895.
21 (a) M. B. Gawande, A. Rathi, P. S. Branco, I. D. Nogueira,
A. Velhinho, J. J. Shrikhande, U. U. Indulkar, R. V. Jayaram,
C. A. A. Ghumman, N. Bundaleski and O. M. N. D. Teodoro,
Chem.–Eur. J., 2012, 18, 12628; (b) M. B. Gawande, R. K. Pandey
and R. V. Jayaram, Catal. Sci. Technol., 2012, 2, 1113; (c)
S. S. Kahandal, S. R. Kale, S. T. Disale and R. V. Jayaram, Catal.
Sci. Technol., 2012, 2, 1493; (d) M. B. Gawande and
P. S. Branco, Green Chem., 2011, 13, 3355.
11 (a) C. Masdeu, E. Gómez, N. A. O. Williams and R. Lavilla,
Angew. Chem., Int. Ed., 2007, 46, 3043; (b) I. Carranco,
J. L. Dıaz, O. Jiménez and R. Lavilla, Tetrahedron Lett., 2003,
44, 8449.
12 R. Lavilla, M. C. Bernabeu, I. Carranco and J. L. Díaz, Org.
Lett., 2003, 5(5), 717.
13 (a) I. Carranco, O. Jiménez and R. Lavilla, Tetrahedron Lett.,
2003, 44(46), 8449; (b) O. Jiménez, G. D. L. Rosa and
R. Lavilla, Angew. Chem., Int. Ed., 2005, 44(40), 6521.
14 (a) L. Singh, M. P. Singh Ishar, M. Elango, V. Subramanian,
V. Gupta and P. Kanwal, J. Org. Chem., 2008, 73, 2224; (b)
V. Sridharan, P. T. Perumal, C. Avendaño and J. C. Menéndez,
Tetrahedron, 2007, 63(21), 4407; (c) G. Bartoli, K. Babiuch,
M. Bosco, A. Carlone, P. Galzerano, P. Melchiorre and
This journal is © The Royal Society of Chemistry 2014
Catal. Sci. Technol., 2014, 4, 672–680 | 679

View Article Online
Paper
Catalysis Science & Technology
22 (a) M. B. Gawande, V. D. B. Bonifacio, R. Luque, P. S. Branco
and R. S. Varma, ChemSusChem, 2013, DOI: 10.1002/
cssc.201300485d; (b) M. B. Gawande, A. Velhinho, I. D. Nogueira,
C. A. A. Ghumman, O. M. N. D. Teodoro and P. S. Branco,
RSC Adv., 2012, 2, 6144.
S. D. Salim, R. V. Sawant and K. G. Akamanchi, Green Chem.,
2010, 12, 1707.
24 (a) S. Maiti, V. Sridharan and J. C. Menendez, J. Comb. Chem.,
2010, 12, 713; (b) V. Sridharan, S. Maiti and J. C. Menendez,
Chem.–Eur. J., 2009, 15, 4565.
23 (a) K. M. Reddy, N. Lingaiah, S. Prasad and I. Suryanarayana,
J. Solution Chem., 2006, 35, 408; (b) P. S. Chaudhari,
25 J. R. Sohn, J. S. Lim and S. H. Lee, Chem. Lett., 2004,
11, 1490–1491.
680 | Catal. Sci. Technol., 2014, 4, 672–680
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