Periodic mesoporous organosilica with ionic-liquid framework supported manganese: An efficient and recyclable nanocatalyst for the unsymmetric Hantzsch reaction

Article abstract of DOI:10.1039/c4ra12673d

An efficient approach for the green and rapid synthesis of biologically active substituted polyhydroquinoline derivatives via unsymmetric Hantzsch reaction using an ionic liquid based periodic mesoporous organosilica supported manganese (Mn@PMO-IL) catalyst under solvent-free conditions is described. This catalyst showed high reactivity and selectivity for the preparation of a set of different derivatives of polyhydroquinolines under moderate reaction conditions and short times. Moreover, the catalyst was also recovered and reused several times without important decrease in reactivity and yields. The nitrogen adsorption-desorption and transmission electron microscopy of the recovered catalyst significantly proved the high stability and durability of the catalyst under applied reaction conditions. Furthermore, compared to the classical methodologies, this method consistently illustrated the advantages of short reaction times, low catalyst loading, high yields, easy separation and purification of the products, and high recoverability and reusability of the catalyst.

Full text of DOI:10.1039/c4ra12673d

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Periodic Mesoporous Organosilica with Ionic-Liquid
Framework Supported Manganese: An Efficient and
Recyclable Nanocatalyst for the Unsymmetric
Hantzsch Reaction
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
M. NasrꢀEsfahani,*a D. Elhamifar,*a T. Amadeh,a and B. Karimib
DOI: 10.1039/x0xx00000x
An efficient approach for the green and rapid synthesis of biologically active substituted
polyhydroquinoline derivatives via unsymmetric Hantzsch reaction using ionic liquid based
periodic mesoporous organosilica supported manganese (Mn@PMOꢀIL) catalyst under
solventꢀfree conditions is described. This catalyst showed high reactivity and selectivity for the
preparation of a set of different derivatives of polyhydroquinolines under moderate reaction
conditions and short times. Moreover, the catalyst was also recovered and reused several times
without important decrease in reactivity and yields. The nitrogen adsorptionꢀdesorption and
transmission electron microscopy of the recovered catalyst significantly proved high stability
and durability of the catalyst under applied reaction conditions. Furthermore, compared to the
classical methodologies, this method consistently illustrated the advantages of short reaction
times, low catalyst loading, high yields, easy separation and purification of the products, and
high recoverability and reusability of the catalyst.
www.rsc.org/
Iodine,16
PTSAꢀSDS,17
tris(pentafluorophenyl)borane,18
Introduction
21
boronic acids,19,20 HClO4/SiO2 and BINOLꢀphosphoric acids.
22
Nevertheless, the problems of environmentally harmful,
expensive and nonꢀreusable catalysts and product separation
limit the use of these homogeneous catalytic systems. To
overcome these drawbacks, recently several attempts have been
successfully developed for the synthesis of polyhydroquinoline
derivatives using efficient and reusable heterogeneous catalysts
under appropriate conditions. Some of applied catalysts are
silicaꢀsupported acids,23,24 ZnO NPs,25 polymers26,27 and Ni
nanoparticles.28 However, some of the later catalytic methods
have disadvantages of high reaction temperature, the use of
ecologically suspected organic solvents and longer reaction
times. Therefore, the developing reaction conditions in the
synthesis of polyhydroquinoline derivatives using efficient and
reusable catalysts under green conditions is still the need of the
day.
On the other hand, organic functionalized ordered mesoporous
silicas with tailored porosity on several length scales are of
interest for a variety applications in areas of adsorption,
chromatography, catalysis, sensor technology, and gas storage
due to their large specific surface area and uniform pore size
with high coverage of introduced functional groups.29,30 Among
different types of organic containing mesoporous silicas,
periodic mesoporous organosilicas (PMOs), which are
synthesized by the simultaneous use of a soft template and a
hydrolysable bisꢀsilane condensing around the template,31 have
mostly progressed the field of material science research. The
unique properties of PMOs such as tuneable chemophysical
Polydroquinolines, as a family of 1,4ꢀdihydropyridine (1,4ꢀ
DHP) derivatives, are one of the most important group of
nitrogen heterocycles that have attracted considerable interest
due to their promising pharmacological and therapeutic
activities such as calcium channel blockers, vasodilator,
bronchodilator, antiatherosclerotic, antitumor, geroprotective,
hepatoprotective, and antidiabetic.1,2 Moreover, some of 1,4ꢀ
dihydropyridines exhibited other medicinal applications which
include platelet antiaggregatory activity,3 neuroprotectant,4
cerebral antischemic activity in the treatment of Alzheimer’s
disease,5 and chemosensitizer acting in tumour therapy.6 As an
example, quinolines having a 1,4ꢀdihydropyridine nucleus are
being used as antiasthamatic, antiinflammatory, antibacterial,
and tyrosine kinase inhibiting agents.7 Furthermore, the
dihydropyridine unit has widely been used as a hydride source
for reductive amination.8 Due to the aforementioned advantages
of the polyhydroquinolines in the biological and chemical
worlds, to date many strategies have been developed for the
synthesis of these compounds. These were firstly prepared by
Hantzsch in 18829 via cyclocondensation reaction between
alkyl acetoacetate, aldehyde and ammonia in acetic acid or by
refluxing in alcohol. In recent years, numerous catalysts have
been successfully reported for the preparation of these
compounds under homogeneous reaction conditions. Some of
ꢀ
these developing catalysts include TMSꢀiodide,10 Bu4N+HSO4
11
,
K7[PW11CoO40],12 ionic liquids,13 metal triflates,14 CAN,15
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properties, high loading of uniform distribution of organic
functional groups in their framework and superior thermal
stability make them attractive candidate for a wide range of
applications in catalysis, electronic, support and adsorption
chemistry.32 In the last decades, ionic liquids (ILs) have
attracted rising interest with a various range of applications in
different areas of chemistry because of their significant
properties such as extremely low volatility, low melting point,
high chemical and thermal stability and high ionic
conductivity.33 However, in spite of the remarkable utility of
these compounds, their widespread applications in process
chemistry is still restricted because many of them are very
expensive.34 Moreover, due to their high viscosity of ionic
liquids only a small amount of them (called diffusion layer)
participates in the chemical process.35 To overcome these
limitations, the concept of supported ionic liquids has been
recently developed. Especially, silica supported ionic liquids
has been successfully developed and applied in several
chemical transformations as an effective support for transition
metal catalysts. Along this regard, more recently we have
prepared a novel periodic mesoporous organosilica with alkyl
imidazolium ionic liquid framework (PMOꢀIL) and studied its
application as effective support for the immobilization and
stabilization of set of different transition metals (M@PMOꢀIL).
The prepared metal containing PMOꢀIL nanomaterials were
then successfully applied as powerful and highly reusable
catalysts in a number of organic reactions such as aerobic
oxidation of alcohols and carbonꢀcarbon bond coupling
processes.36,37 In continuation of our study on applications of
metal supported PMOꢀIL, herein the catalytic application of a
manganese containing ionic liquidꢀbased periodic mesoporous
organosilica (Mn@PMOꢀIL) material is investigated in the
synthesis of polyhydroquinoline derivatives. This was achieved
by the oneꢀpot condensation of aldehydes (aromatic, aliphatic,
Results and discussion
The PMOꢀIL nanomaterial was first prepared by hydrolysis and
coꢀcondensation of 1,3ꢀbis(3ꢀtrimethoxysilylpropyl)
imidazolium iodide and tetramethoxysilane in the presence of
Pluronic P123 under acidic conditions.37 The PMOꢀIL
nanomaterial was then reacted with a subꢀstoichiometric
amount of manganese acetate in DMSO solvent, according to
our recently reported procedure, to produce the Mn@PMOꢀIL
nanocatalyst (Scheme 1).38 This catalyst was then characterized
with some techniques such as infrared (IR) spectroscopy,
thermal gravimetric analysis (TGA), powder Xꢀray diffraction
(PXRD), transmission electron microscopy (TEM) and energy
dispersive Xꢀray (EDX) spectroscopy. The IR spectrum of the
Mn@PMOꢀIL was performed to investigate the presence of
organic functional groups in the material framework (Figure 1).
This showed bands at 1147, 1073 and 952 cm−1 corresponding
to asymmetric and symmetric vibrations of SiꢀOꢀSi bonds.36c
The strong and broad signal cleared about 3300 cm−1 is
attributed to OꢀH bonds of siloxane groups. The bands observed
at 2933 and 2859 cm−1 are assigned to CꢀH stretching of
aliphatic moieties. Moreover, the signals cleared at 1563 and
1635 cm−1 are, respectively, attributed to C=C and C=N
stretching vibrations of imidazolium ring.36c,36e These
observations successfully confirm victorious incorporation of
alkyl imidazolium ionic liquid groups in the material
framework.
unsaturated
and
heterocyclic),
5,5ꢀdimethylꢀ1,3ꢀ
cyclohexanedione (dimedone) or 1,3ꢀcyclohexanedione, βꢀ
dicarbonyl and ammonium acetate in the presence of
Mn@PMOꢀIL nanocatalyst under solvent free conditions
(Scheme 1). Moreover the reactivity, reusability and stability of
the catalyst during reaction process have also been studied in
detail.
Figure 1. IR spectrum of the Mn@PMOꢀIL nanocatalyst
Thermal gravimetric analysis (TGA) of the Mn@PMOꢀIL was
performed to investigate the thermal stability of the material
(Figure 2). This analysis illustrated a weight loss of 6.64 % in
°
the temperature below 120 C corresponding to removal of
water. A very small weight loss (2.28 %) between 120 and 280
°C is attributed to elimination of surfactant template remained
from extraction process. The third weight loss (18.35 %) from
°
280 to 800 C is related to removal of ionic liquid functional
groups located in the material framework. This data
successfully proves the successful incorporation of organic
functional moieties in the solid network and confirms high
thermal stability of the material.
Scheme 1. Preparation of the Mn@PMOꢀIL nanocatalyst and its
application in synthesis of polyhydroquinolines
2 | J. Name., 2012, 00, 1-3
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Figure 2. Thermal gravimetric analysis (TGA) of the Mn@PMOꢀIL
nanocatalyst.
The PXRD analysis of the material demonstrated a single high
intensity peak at 2θ 0.7–1.3 which indexed as the d100 reflection
and matches with the 2ꢀdimensional hexagonal materials having long
range periodicity (Figure 3). This significantly proves the presence
of uniform mesostructure with high regularity. The transmission
electron microscopy (TEM) image of the Mn@PMOꢀIL was in
good agreement with PXRD analysis and successfully
confirmed a two dimensional hexagonal structure with high
regularity for the material (Figure 4). Furthermore, this image
together with PXRD analysis proved the high stability of the
material structure after immobilization of manganese species
onto/into the mesopores.
Figure 4. Transmission electron microscopy (TEM) image of
Mn@PMOꢀIL
Energyꢀdispersive Xꢀray (EDX) spectroscopy showed the
presence of C, O, Si, S, Cl and Mn in the Mn@PMOꢀIL
nanocatalyst (Figure 5). The elemental distribution mapping of
this analysis shows signals of carbon: oxygen: silicon: sulfur:
chlorine: manganese in the ratio of 34.2: 44.9: 16.7: 0.9: 1.3:
1.9 wt%, respectively. This confirms successful incorporation
of expected elements in the material network. It is also important
to note that the Xꢀray photoelectron spectroscopy (XPS) of the
catalyst showed peaks at binding energies of 654.2 and 642.6 eV for
the Mn 2p1/2 and Mn 2p3/2, respectively, confirming that Mn species
are strongly bound to electronegative atoms and may be they are as
Mn(III).38
Figure 5. Energy dispersive Xꢀray (EDX) spectroscopy of the
Mn@PMOꢀIL
Effect of catalyst loading, solvent and temperature in the
synthesis of polyhydroquinolines
After characterization, the catalytic activity of Mn@PMOꢀIL in
the synthesis of polyhydroquinolines under different reaction
conditions was investigated. For comparison of the results
between solvent and solventꢀfree conditions, the solvent effect
in the condensation of dimedone (1mmol), benzaldehyde (1
mmol), ethylacetoacetate (1 mmol) and ammonium acetate (1
mmol) in the presence of Mn@PMOꢀIL (1 mol%), as a test
model, was studied. As shown in Table 1, among the applied
solvents such as ethanol, methanol, water, chloroform and a
solventꢀfree system, the best result was obtained after 20 min
under solventꢀfree conditions in excellent yield (Table 1, entries
1ꢀ5). With this optimistic result in hand, we then investigated
the best reaction conditions by using different amounts of
catalyst. An increase in the quantity of Mn@PMOꢀIL from 0.35
to 1 mol % also increased the product yield from 35% to 95%
(Table 1, entries 5ꢀ7).
Figure 3. Powder Xꢀray diffraction (PXRD) of Mn@PMOꢀIL
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Table 1. Catalytic activity evaluation and the effect of temperature and
with nearly equal ease. As shown, benzaldehyde substrates
containing activating substituents such as OH (Table 2, entries
6, 12 and 19), CH3O (Table 2, entry 21) and CH3 (Table 2,
entries 8, 14 and 23) furnished high yields of corresponding
coupling adducts. Benzaldehyde (Table 2, entries 1, 5, 9 and
23) also gave satisfactory yields of related products. Moreover,
other aldehyde substrates containing deactivating substituents
such as NO2 (Table 2, entries 2, 10 and 22) and Cl (Table 2,
entries 4, 13, 18 and 20) delivered high yields of corresponding
coupling products. In addition, the aliphatic aldehydes such as
butanal (Table 2, entry 15) afforded a 55% yield in 100 min.
Also acidꢀsensitive substrates such as cinnamaldehyde
proceeded well to give the corresponding polyhydroquinolines
without any side products (Entry 17). Furthermore, the
procedure worked well for heterocyclic aldehydes (Table 2,
entries 3, 7, 11 and 16). These observations strongly confirm
high efficiency and powerful activity of the present catalyst for
a broad range of aldehydes to produce different derivatives of
polyhydroquinolines which are important and applicable in
drug chemistry.
solvent in the synthesis of polyhydroquinolinesa
Entry Mn@PMOꢀIL Temp.
Solvent
Time Yieldb
(mol%)
(
°C
)
(min)
(%)
1
2
3
1
1
1
reflux
reflux
reflux
ethanol
metanol
water
30
30
30
53
48
45
4
1
reflux chloroform
30
38
5
6
7
8
9
10
11
1
0.7
0.35
None
1
80
80
80
80
60
45
80
-
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
20
20
20
120
20
20
60
20
95
67
35
Trace
53
30
25
95
1
PMOꢀIL
12 Mn(OAc)3.2H2O 80
a
Reaction conditions: dimedone (1 mmol), benzaldehyde (1 mmol),
ethylacetoacetate (1 mmol), ammonium acetate (1 mmol) and catalyst
in mol%. b Isolated yields.
Since the reusability of the catalysts is an important benefit and
makes them useful for commercial applications, in the next
study the recovery and reusability of Mn@PMOꢀIL were
investigated. For this, the reaction of dimedone, benzaldehyde,
ethylacetoacetate and ammonium acetate in the presence of 1
mol% catalyst was selected as a test model. To achieve the
reaction efficiency of recovered catalyst, after completion of the
reaction, the obtained mixture was filtered and washed
completely with ethanol to give the catalyst. The recovered
catalyst was dried and then used again in the same reaction that
led to the yield of 94%. The more investigations showed that
the catalyst could be recovered and reused, under the same
conditions of the fresh run, for at least five times without any
considerable loss in activity (Figure 6A). Also, reꢀactivity of
the catalyst was investigated (Figure 6B). To do this,
The study also showed that the catalyst loading plays a key role in
the reaction progress (Table 1, entries 5ꢀ7). It is also important to
note, in the absence of catalyst at 120 min under the same conditions
as before, only a trace amount of product was obtained (Table 1,
entry 8). Furthermore, by using PMOꢀIL instead of Mn@PMOꢀIL as
catalyst, the rate of the model reaction was significantly decreased
and a lower yield of product was obtained after 60 min (Table1,
entry 11). On the other hand, applying of Mn(OAc)3.2H2O as
catalyst gave excellent yield of the product (Table1, entry 12),
however, this is not recoverable and reusable for the next runs.
These observations show that the reaction cycle is mainly catalyzed
by manganese species immobilized on the PMOꢀIL nanostructure.
Accordingly, in all further reactions 1 mol% of the Mn@PMOꢀIL
catalyst was used because of satisfactory yield of the product in
reasonably short time.
Mn@PMOꢀIL was added to
benzaldehyde, ethylacetoacetate and ammonium acetate and the
reaction mixture was heated in 80 C. After completion of the
a mixture of dimedone,
Our study also showed that the reaction was also effected by
the amount of heat and the best result was observed at 80 C
°
°
(Table 1, entry 5 vs. entries 9, 10). In another study, the
reaction was performed using different quantities of reagents.
This showed that the best result is obtained with a 1:1:1:1 ratio
of dimedone, benzaldehyde, ethyl acetoacetate and ammonium
acetate, respectively.
reaction, monitored by TLC, the fresh amounts of starting
materials were added to the previous reaction mixture in the
flask and stirring and heating were carried out to complete the
second cycle. These cycles were occurred to ten times without
noticeable decrease in yield of the reactions (Figure 6B). These
observations significantly prove high recoverability, reusability,
reactivity and stability of the present catalyst under applied
reaction conditions. This may be attributed to ionic liquid
ligands and mesopore channels of PMOꢀIL material that protect
catalytic manganese species against leaching and deactivation.
To demonstrate the generality of this method, we next
investigated the scope of this reaction under the optimized
°
conditions (Mn@PMOꢀIL 1 mol%, solventꢀfree, 80 C). As
shown in Table 2, this method was equally effective
irrespective of the nature and positions of the substituents
attached to the phenyl ring of the aromatic aldehyde. All
strongly activating (4c
activating (4h 4n 4x), weakly deactivating (4d
and strongly deactivating (4b 4j 4v) substrates gave products
,
4f
,
4g
,
4k
,
4l,
4p
,
4s
,
4u), weakly
,
,
,
4m 4r 4t),
,
,
,
,
Table 2. Synthesis of polyhydroquinoline derivatives in the presence of Mn@PMOꢀIL catalysta
Mp (˚C)
Entry
R1
R2
R3
Compounds Time (min) Yield (%)b
Found
241ꢀ242
203ꢀ205
Reported
240ꢀ241
204ꢀ205
1
2
C6H5
4ꢀNO2C6H4
H
H
OEt
OEt
20
25
90
90
4a
4b
4 | J. Name., 2012, 00, 1-3
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3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2ꢀThienyl
4ꢀClC6H4
C6H5
3ꢀHOC6H4
2ꢀFuryl
H
H
H
H
H
OEt
OEt
Me
15
20
45
35
20
20
20
20
20
20
20
20
100
20
28
20
20
20
20
20
20
20
92
87
80
87
95
89
95
88
90
92
92
88
55
92
87
85
91
85
87
85
90
86
232ꢀ233
234ꢀ236
227ꢀ230
244ꢀ246
212ꢀ216
218ꢀ220
202ꢀ204
243ꢀ245
239ꢀ241
220ꢀ222
207ꢀ209
260ꢀ262
147ꢀ149
247ꢀ248
204ꢀ206
240ꢀ243
202ꢀ204
219ꢀ222
258ꢀ260
232ꢀ234
209ꢀ211
268ꢀ271
233ꢀ234
234ꢀ235
229ꢀ230
ꢀ
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
Me
OMe
OMe
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
ꢀ
ꢀ
4ꢀCH3C6H4
C6H5
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
203ꢀ204
244ꢀ246
237ꢀ239
218ꢀ220
206ꢀ208
261ꢀ263
147ꢀ148
246ꢀ248
205ꢀ207
241ꢀ244
200ꢀ202
220ꢀ222
259ꢀ261
234ꢀ236
212ꢀ214
270ꢀ274
4ꢀNO2C6H4
2ꢀThienyl
3ꢀHOC6H4
2ꢀClC6H4
4ꢀCH3C6H4
CH3CH2CH2
2ꢀFuryl
4m
4n
4o
4p
4q
4r
4s
C6H5–CH=CH
2,4ꢀCl2C6H3
3ꢀCH3Oꢀ4ꢀHOC6H4 Me
4ꢀClC6H4
4ꢀCH3OC6H4
3ꢀNO2C6H4
C6H5
Me OMe
Me OMe
Me OMe
Me OMe
Me OMe
4t
4u
4v
4w
4x
4ꢀCH3C6H4
aAll products were characterized by 1H NMR, 13C NMR and IR spectroscopy and comparison with these reported in the
literature. 15,26,28,39,40
b Isolated yields.
significantly illustrated a uniform and regular mesopores which
is characteristics of two dimensional hexagonal structures
(Figure 8). These observations strongly confirm high stability
and recoverability of the Mnꢀnanocatalyst under applied
reaction conditions. The high activity, recoverability and
stability of the present catalytic system may be attributed to
ionic liquid nature of the PMOꢀIL as well as uniform
mesoporous channels of the material, which effectively
immobilize the active Mn species and protect them against
leaching and deactivation.
Figure 6. (A) Reusability and (B) Reꢀactivity of the Mn@PMOꢀIL
nanocatalyst in the synthesis of 4i
The recovered catalyst after third reaction cycle was analyzed
by transmission electron microscopy and nitrogen adsorptionꢀ
desorption experiment. The nitrogen adsorptionꢀdesorption
analysis showed a type IV isotherm with H1 hysteresis loop and
high intensity in relative pressure of 0.4ꢀ0.6 (Figure 7). The
BET surface and mean pore volume of this material was found
to be 435 m2/g and 8.54 cm3/g, respectively. Moreover, the BJH
calculations also illustrated a peak with high intensity and mean
pore diameter of 6 nm confirming the presence of uniform
pores in the mesoꢀrange (Figure 7). The TEM image of this
material was in good agreement with nitrogen sorption data and
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O
R
O
N
H
9
7
O
R1
O
O
H2O
+
H O
2
+AcO
H
R3
R2
H2N
R2
6
5
Step 1
Step 3
Step 2
R1CHO
NH4OAc
R2
1
O
O
O
R1
O
R3
R3
R2
O
3
O
R2
N
2
R2
6
H
4
NH4OAc
R1CHO
Step 5
Step 4
Step
O
O
R3
R1
+
H2O
R2
NH2
H2O + AcOH
O
R2
8
7
: Mn@PMOꢀIL
Figure 7. Nitrogen adsorptionꢀdesorption (top) and BJH pore size
distribution (bottom) isotherms of recovered Mn@PMOꢀIL after
third reaction cycle
[Mn]
[Mn]
R1
[Mn]
O
R1
O
O
R1
OH
O
O
O
R2
R2
R2
R2
R2
H
O
- H2O
R2
O
O
7
R2
R2
R1
O
O
O
O
O
R1
O
H
R3
R1
R3
- H2O
R3
+
H2N
R2
R2
R2
O
N
R2
OH
HN
R2
H
R2
8
[Mn]
4
[Mn]
Scheme 2. Plausible mechanism of catalytic synthesis of
polyhydroquinolines using Mn@PMOꢀIL
Experimental
Figure 8. TEM image of recovered Mn@PMOꢀIL catalyst after third
reaction cycle
Synthetic procedures, Materials and methods
A proposed mechanism for the Mn@PMOꢀIL nanocatalyst
catalyzed synthesis of polyhydroquinolines is presented in
Scheme 2. The role of catalyst is shown in steps 1 and 5 where
it catalyzes the Knoevenagel type coupling of aldehydes with
Chemicals were purchased from Merck, Fluka and Aldrich
chemical companies. Melting points were determined using a
Barnstead Electrothermal (BI 9300) apparatus and are
uncorrected. IR spectra were obtained using a FTꢀIR JASCOꢀ
680 spectrometer instrument. NMR spectra were taken with a
Bruker 400 MHz Ultrashield spectrometer at 400 MHz (1H) and
100 MHz (13C) using CDCl3 or DMSOꢀd6 as the solvent with
TMS as the internal standard. TEM image was taken on a FEI
Tecnai 12 BioTWIN microscope operated at 120 kV. The
thermal gravimetric analysis (TGA) was measured by
NETZSCH STA 409 PC/PG from room temperature to 800 °C.
active methylene compounds and in steps
catalyzes the Michael type addition of intermediates
to give product . The formation of acridinedione
when
reacts with 7,41 since this possibility is discarded due to
nonꢀformation of intermediates A literature survey
and 6 42
3
and
6
where it
5
,
6
or
7, 8
4
9 is possible
5
5
.
also adjusts with absence of acridinediones as a byꢀproduct
during present reaction.10ꢀ28
Preparation of manganese supported ionic liquid based periodic
meoporous organosilica (Mn@PMO-IL) catalyst.
To do this, firstly the PMOꢀIL nanomaterial was prepared according
to our previous reported procedure.37 Then Mn(OAc)3.2H2O (0.5
mmol)) was added to a monodispersed solution of PMOꢀIL material
(1g, 1.0 mmol IL/g) in DMSO (4.5 mL) under argon atmosphere.
The mixture was first stirred at 50 ° for 6 h and then at 100 °
C C for 2
6 | J. Name., 2012, 00, 1-3
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h. After that, the reaction solution was cooled to room temperature In a flask containing benzaldehyde (1 mmol), ethylacetoacetate
(1 mmol), dimedone (1 mmol) and ammonium acetate (1mmol)
1 mol% of Mn@PMOꢀIL nanocatalyst was added and the
mixture was stirred at 80 C. After completion of the reaction,
the mixture was added to hot ethanol and the obtained solution
was hotly filtered and completely was washed with ethanol.
The catalyst was then recovered and reused at the same
conditions as the first run for at least 5 reaction cycles and
delivered corresponding product in high yield and selectivity.
and the resulting mixture was filtered and washed completely with
ethanol to remove unsupported Mn(OAc)3.2H2O. The final material
was obtained after drying by evacuation at 60 °C for 12 h and
denoted as Mn@PMOꢀIL.38
°
General procedure for the preparation of polyhydroquinolines
In
a roundꢀbottomed flask the aldehyde (1mmol), 1,3ꢀ
cyclohexanedione derivatives (1 mmol), ammonium acetate (1
mmol), βꢀdicarbonyl (1 mmol) and Mn@PMOꢀIL nanocatalyst
1 mol%) were mixed thoroughly. The flask was heated at 80 °C
with concomitant stirring. After completion of the reaction
Conclusions
We have described the catalytic application of a manganese
containing ionic liquidꢀbased ordered mesoporous organosilica
(Mn@PMOꢀIL) in the unsymmetric Hantzsch reaction. The
reaction system was significantly affected by catalyst loading,
reaction temperature and solvent. The catalyst illustrated high
efficiency and reactivity for the synthesis of substituted
polyhydroquinoline derivatives using a variety of activated and
deactivated aldehyde, 1,3ꢀcyclohexanedione derivatives,
ammonium acetate and βꢀdicarbonyls under solventꢀfree
conditions. In addition, the catalyst could be recovered and
reused at least five times with no decrease in its activity and
selectivity. Also, investigation of the reꢀactivity of the catalyst
showed that the repeating cycles could be occurred to ten times
without noticeable decrease in times and yields of the reactions.
Therefore, the attractive features of this protocol are simple
procedure, short reaction times, high yields, simple workup,
reusability and reꢀactivity of the catalyst and simple purification
of the products.
confirmed by TLC (eluent: EtOAc:nꢀhexane), hot ethanol (5
mL) was added and the obtained solution was filtered and
completely washed with ethanol. The solvent was then
evaporated and the crude products were recrystallized in
ethanol and gave pure crystals in 80ꢀ95% yields based on the
1
starting aldehyde. The products were characterized by IR, H
NMR, 13C NMR and via comparison of their melting points
with the reported ones. Spectroscopic data of new compounds
are as following:
2-Methyl-3-acetyl-5-oxo-4-(3-hydroxyphenyl)-1,4,5,6,7,8-
hexahydroquinoline (4f)
Mp: 244ꢀ246 ˚C; Rf = 0.31 (nꢀhexane:ethyl acetate = 3:1); IR
(KBr): 3417, 3255, 3202, 2960, 1665, 1613, 1478, 1222 cmꢀ1;
1H NMR (400MHz, DMSOꢀd6)
δ
(ppm): 1.91ꢀ2.15 (m, 2H),
2.18 (s, 3H), 2.25 (t,
J
= 11.2 Hz, 2H), 2.41 (s, 3H), 2.46 (t,
J =
7.9 Hz, 2H), 5.24 (s, 1H), 7.08ꢀ7.30 (m, 4H), 9.11 (s, 1H); 13C
NMR (100MHz) δ (ppm): 18.79, 26.24, 29.13, 29.88, 31.95,
35.22, 50.24, 109.86, 113.09, 127.05, 127.58, 129.26, 131.14,
131.46, 142.74 ,144.55, 149.44, 193.78, 197.91; Anal. Calcd.
for C18H19NO3: C, 72.71; H, 6.44; N, 4.71; O, 16.14; found: C
72.62, H 6.37, N 4.80.
Acknowledgements
The authors thank the Yasouj University and the Iran National
Science Foundation (INSF) for supporting this work.
2-Methyl-5-oxo-4-(2-furyl)-1,4,5,6,7,8-hexahydroquinoline-
3-carboxylic acid methyl ester (4g)
Notes and references
a
Department of Chemistry, Yasouj University, Yasouj, 75918ꢀ74831,
Mp: 212ꢀ216 ˚C; Rf = 0.40 (nꢀhexane:ethyl acetate = 3:1); IR
Iran.
(KBr): 3285, 3079, 2944, 1698, 1649, 1608, 1483, 1220 cmꢀ1;
b Department of Chemistry, Institute for Advanced Studies in Basic Sciences
(IASBS), 45137ꢀ6731, Gava Zang, Zanjan, Iran
1H NMR (400 MHz, DMSOꢀd6)
δ
(ppm): 0.91ꢀ1.15 (m, 2H),
1.93 (t,
J
= 6.5 Hz, 2H), 2.26 (s, 3H), 2.51 (t, = 4.0 Hz, 2H),
J
3.60 (s, 3H), 5.06 (s, 1H), 5.79ꢀ5.83 (m, 1H), 6.19ꢀ6.25 (m,
1H), 7.32ꢀ7.40 (m, 1H), 9.25 (s, 1H); 13C NMR (100MHz) δ
(ppm):18.16, 20.78, 26.11, 29.35, 36.58, 50.78, 100.24, 104.0,
107.71, 109.43, 141.18, 146.03, 152.26, 158.29, 167.09,
194.42; Anal. Calcd. for C16H17NO4: C, 66.89; H, 5.96; N,
4.88; O, 22.27; found: C 66.78, H 5.89, N 4.95.
1
2
(a) F. Bossert, H. Meyer and E. Wehinger, Angew. Chem. Int.
Ed. Engl., 1981, 20, 762ꢀ769; (b) H. Nakayama and Y.
Kasoaka, Heterocycles, 1996, 42, 901ꢀ909.
(a) T. Godfraid, R. Miller and M. Wibo, Pharmocol. Rev.
,
1986, 38 321ꢀ416; (b) A. Sausins and G. Duburs,
,
2-Methyl-5-oxo-4-(4-methylphenyl)-1,4,5,6,7,8-
Heterocycles, 1988, 27, 269ꢀ289; (c) P. P. Mager, R. A.
Coburn, A. J. Solo, D. J. Triggle and H. Rothe, Drug Design
hexahydroquinoline-3-carboxylic acid methyl ester (4h)
Mp: 218ꢀ220 ˚C; Rf = 0.33 (nꢀhexane:ethyl acetate = 3:1); IR
(KBr): 3286, 2960, 1716, 1671, 1605, 1379, 1225 cmꢀ1; 1H
Discov., 1992, 8, 273ꢀ289; (d) R. Mannhold, B. Jablonka, W.
Viogdt, K. Schoenafinger and K. Schravan, Eur. J. Med.
Chem., 1992, 27, 229ꢀ235.
NMR (400 MHz, DMSOꢀd6)
(t, = 4.2 Hz, 2H), 2.26 (s, 3H), 2.28 (s, 3H), 2.47 (t,
Hz, 2H), 3.52 (s, 3H), 4.87 (s, 1H), 6.97 (d, = 7.8 Hz,
2H),7.02 (q,
= 7.93 Hz, 2H), 9.13 (s, 1H); 13C NMR(100
δ
(ppm): 1.70ꢀ1.92 (m, 2H), 2.18
J
J
= 7.7
J
3
R. G. Bretzel, C. C. Bollen, E. Maeser and K. F. Federlin, Am.
J. Kidney Dis., 1993, 21, 53ꢀ64.
J
MHz) δ (ppm):18.14, 20.52, 26.08, 31.64, 34.90, 50.60, 103.24,
111.23, 111.26, 112.58, 127.09, 128.45, 134.53, 144.74,
145.03, 151.16, 167.38, 194.61; Anal. Calcd. for C19H21NO3: C,
73.29; H, 6.80; N, 4.50; O, 15.41; found: C 73.19, H 6.72, N
4.57.
4
5
V. Klusa, Drugs Future, 1995, 20, 135ꢀ138.
R. G. Bretzel, C. C. Bollen, E. Maeser and K. F. Federlin,
Drugs Future, 1992, 17, 465ꢀ468.
6
7
R. Boer and V. Gekeler, Drugs Future, 1995 20, 499ꢀ509.
(a) Y. L. Chen, K. C. Fang, J. Y. Sheu, S. L. Hsu and C. C.
Tzeng, J. Med. Chem., 2001, 44, 2374ꢀ2377; (b) G. Roma, M.
D. Braccio, G. Grossi and M. Chia, Eur. J. Med. Chem., 2000,
General procedure for the recovery of Mn@PMO-IL
nanocatalyst in the polyhydroquinolines synthesis
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ARTICLE
DOI: 10.1039/C4RA12673D
35, 1021ꢀ1035; (c) M. P. Maguire, K. R. Sheets, K. McVety,
A. P. Spada and A. Zilberstein, J. Med. Chem., 1994, 37, 2129ꢀ
2137.
34 D. B. Zhao, Y. C. Liao and Z. D. Zhang, Clean: Soil, Air,
Water, 2007, 35, 42ꢀ48.
35 A. Riisager, R. Fehrmann, S. Flicker, R. van Hal, M. Haumann
and P. Wasserscheid, Angew. Chem. Int. Ed., 2005, 44, 815ꢀ
819.
8
9
T. Itoh, K. Nagata, M. Miyazaki, H. Ishikawa, A. Kurihara and
A. Ohsawa, Tetrahedron, 2004, 60, 6649ꢀ6655.
A. Hantzsch, Ann. Chem., 1882, 215, 1ꢀ82.
36 (a) B. Karimi, D. Elhamifar, J. H. Clark and A. J. Hunt, Chem.
Eur. J., 2010, 16, 8047ꢀ8053; (b) B. Karimi, D. Elhamifar, J.
10 G. Sabitha, G. S. K. K. Reddy, C. S. Reddy and J. S. Yadav,
Tetrahedron Lett., 2003, 44, 4129ꢀ4131.
H. Clark and A. J. Hunt, Org. Biomol. Chem., 2011,
7426; (c) B. Karimi, D. Elhamifar, O. Yari, M. Khorasani, H.
Vali, J. H. Clark and A. J. Hunt, Chem. Eur. J., 2012, 18
13520ꢀ13530; (d) D. Elhamifar, F. Hosseinpoor, B. Karimi and
S. Hajati Microporous Mesoporous Mater. 2015, 204 269ꢀ275;
9, 7420ꢀ
11 N. Tewari, N. Dwivedi and R.P. Tripathi, Tetrahedron Lett.
2004, 45, 9011ꢀ9014.
,
,
12 M. M. Heravi, K. Bakhtiari, N. M. Javadi, F. F. Bamoharram,
M. Saeedi and H. O. Oskooie, J. Mol. Catal. A: Chem., 2007,
264, 50ꢀ52.
,
,
(e) D. Elhamifar, B. Karimi, A. Moradi and J. Rastegar,
ChemPlusChem 2014, 79, 1147ꢀ1152.
13 S. J. Ji, Z. Q. Jiang, J. Lu and T. P. Loh, Synlett, 2004, 831ꢀ
835.
37 D. Elhamifar, B. Karimi, J. Rastegar and M. H. Banakar,
14 L. M. Wang, J. Sheng, L. Zhang, J. W. Han, Z. Fan, H. Tian,
C. T. Qian, Tetrahedron, 2005, 61, 1539ꢀ1543.
15 S. Ko and C. F. Yao, Tetrahedron Lett., 2006, 62, 7293ꢀ7299.
16 S. Ko, M. N. V. Sastry, C. Lin and C. F. Yao, Tetrahedron
Lett., 2005, 46, 5771ꢀ5774.
ChemCatChem, 2013, 5, 2418ꢀ2424.
38 D. Elhamifar and A. Shábani, Chem. Eur. J., 2014, 20, 3212ꢀ
3217.
39 A. Khojastenezhad, F. Moeinpour and A. Davoodnia, Chin.
Chem. Lett., 2011, 22, 807ꢀ810.
17 A. Kumar and R. A. Maurya, Synlett, 2008, 883ꢀ885.
18 S. Chandrasekhar, Y. S. Rao, L. Sreelakshmi, B. Mahipal and
C. R. Reddy, Synthesis, 2008, 1737ꢀ1741.
40 L. M. Wang, J. Sheng, L. Zhang, J. W. Han, Z.Y. Fan and H.
Tian, Tetrahedron, 2005, 61, 1539ꢀ1543.
41 G. W. Wang and C. B. Miao, Green Chem., 2006, 8, 1080ꢀ
19 R. Sridhar and P. T. Perumal, Tetrahedron, 2005, 61, 2465ꢀ
2470.
1085.
42 K. A. Undale, T. S. Shaikh, D. S. Gaikwad and D. M. Pore, C.
R. Chimie, 2011, 14, 511ꢀ515.
20 A. Debache, R. Boulcina, A. Belfaitah, S. Rhouati and B.
Carboni, Synlett, 2008, 509ꢀ512.
21 M. Maheswara, V. Siddaiah, G. L. V. Damu and C. V. Rao,
Arkivoc, 2006, 2, 201ꢀ206.
22 C. G. Evans and J. E. Gestwicki, Org. Lett., 2009, 11, 2957ꢀ
2959.
23 M. Maheswara, V. Siddaiah, Y. K. Rao, Y. Tzeng and C.
Sridhar, J. Mol. Catal. A: Chem., 2006, 260, 179ꢀ180.
24 R. Gupta, S. Paul and A. Loupy, Synthesis, 2007, 2835ꢀ2838.
25 M. Z. Kassaee, H. Masrouri and F. Movahedi, Monatsh.
Chem., 2010, 141, 317ꢀ322.
26 J. G. Brietenbucher, G. Figliozzi, Tetrahedron Lett., 2000, 41
,
4311ꢀ4314.
27 A. Dondoni, A. Massi, E. Minghini and V. Bertolasi,
Tetrahedron, 2004, 60, 2311ꢀ2326.
28 B. S. Sapkal, K. F. Shelke, B. B. Shingate and M. S. Shingare,
Tetrahedron Lett., 2009, 50, 1754ꢀ1756.
29 F. Hoffmann, M. Corneluis, J. Morell, M. Froba, Angew.
Chem. Int. Ed., 2006, 45, 3216ꢀ3251.
30 X. S. Zhao, G. Q. Lu and H. Y. Zhu, 24th Australia and New
Zealand Chemical Engineering Conference and Exhibition
,
1996, , 39.
4
31 S. Fujita and S. Inagaki, Chem. Mater. 2008, 20, 891; S. E. Hankari,
B. MotosꢀP_rez, P. Hesemann, A. Bouhaouss and J. J. E. Moreau,
Chem. Commun., 2011, 47, 6704ꢀ6706.
32 (a) Q. Yang, J. Liu, L. Zhang and C. Li, J. Mater. Chem. 2009, 19,
1945ꢀ1955; (b) F. Hoffmann and M. Fröba, Chem. Soc. Rev. 2011, 40,
608ꢀ620; (c) M. S. Moorthy, S. S. Park, D. Fuping, S. H. Hong, M.
Selvaraj and C. S. Ha, J. Mater. Chem. 2012, 22, 9100ꢀ9108.
33 H. OlivierꢀBourbigou, L. Magna and D. Morvan, Appl. Catal.
A: Gen., 2010, 373, 1ꢀ56.
8 | J. Name., 2012, 00, 1-3
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We have described the catalytic application of a manganese containing ionic liquid-based
ordered mesoporous organosilica in the synthesis of polyhydroquinolines.