Fast and Solvent-Free Synthesis of Polyhydroquinolines Catalyzed by a Keplerate Type Giant Nanoporous Isopolyoxomolybdate as a Reusable Catalyst

Article abstract of DOI:10.1080/15533174.2015.1004419

A novel application of (NH₄)₄₂[Mo^VI₇₂Mo^V₆₀O₃₇₂(CH₃COO)₃₀(H₂O)₇₂] catalyst, a Keplerate type giant nanoporous isopolyoxomolybdate, deno

Full text of DOI:10.1080/15533174.2015.1004419

Synthesis and Reactivity in Inorganic, Metal-Organic, and
Nano-Metal Chemistry
ISSN: 1553-3174 (Print) 1553-3182 (Online) Journal homepage: http://www.tandfonline.com/loi/lsrt20
Fast and Solvent-Free Synthesis of
Polyhydroquinolines Catalyzed by a Keplerate
Type Giant Nanoporous Isopolyoxomolybdate as a
Reusable Catalyst
Abolghasem Davoodnia & Ahmad Nakhaei
To cite this article: Abolghasem Davoodnia & Ahmad Nakhaei (2015): Fast and Solvent-
Free Synthesis of Polyhydroquinolines Catalyzed by a Keplerate Type Giant Nanoporous
Isopolyoxomolybdate as a Reusable Catalyst, Synthesis and Reactivity in Inorganic, Metal-
Organic, and Nano-Metal Chemistry, DOI: 10.1080/15533174.2015.1004419
To link to this article: http://dx.doi.org/10.1080/15533174.2015.1004419
Accepted author version posted online: 29
Oct 2015.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsrt20
Download by: [University of Nebraska, Lincoln]
Date: 03 November 2015, At: 00:58

ACCEPTED MANUSCRIPT
Fast and Solvent-Free Synthesis of Polyhydroquinolines Catalyzed by a Keplerate Type
Giant Nanoporous Isopolyoxomolybdate as a Reusable Catalyst
AbolghasemDavoodnia*, Ahmad Nakhaei
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
*Corresponding author. E-mail: adavoodnia@mshdiau.ac.ir; adavoodnia@yahoo.com
A novel application of (NH4)42[MoVI72MoV60O372(CH3COO)30(H2O)72] catalyst, a
Keplerate type giant nanoporous isopolyoxomolybdate, denoted as ({Mo132}), in the synthesis of
polyhydroquinolines is reported. The catalyst was prepared using inexpensive and readily
available materials and characterized using FT-IR, and UV spectra. The results showed that this
catalyst has high catalytic activity and the desired products were obtained within a few seconds
or minutes (for some cases) in high yields under solvent-free conditions at 120 ºC. Furthermore,
the catalyst could be recycled after a simple work-up, and reused at least four times without
significant reduction in its catalytic activity.
Keywords
Giant nanoporous isopolyoxomolybdate, Keplerate, {Mo132}, Polyhydroquinolines.
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
INTRODUCTION
Organic syntheses involving greener process and under solvent-free conditions have been
investigated worldwide due to stringent environment and economic regulations.[1-3] In addition,
maximizing synthetic efficiency by designing a complexity generating diversity-oriented
synthesis is gaining more and more importance in organic synthesis and drug discovery. For this
purpose, development and utilization of multicomponent reactions (MCRs) are of prime
importance.[4-6] Generally, a product in a MCR is assembled according to a cascade of
elementary chemical reactions. Thus, there is a network of reaction equilibria, in which all the
starting materials finally flow into an irreversible step yielding the product. The challenge is thus
to conduct a MCR in such a way that the network of preequilibrated reactions channels into the
main product and does not yield side products.[7] Thus, the developing of new MCRs and
improving known MCRs are popular areas of research in current organic chemistry.
The principles of green chemistry have been introduced to eliminate or at least to reduce
the use of hazardous materials, such as H2SO4 or H3PO4 in chemical processes. Cleaner
technologies could become possible by making use of the environmental friendly materials, such
as the use of solid acids. These catalysts have many advantages over liquid acid catalysts.[8] They
are not corrosive but environmentally benign, presenting fewer disposal problems. Thus the
development and use of solid green catalysts are very important in organic syntheses.
Polyoxometalates (POMs), constituting a large class of metal oxide molecules, are known
to have a variety of sizes, structures, electrochemical properties, and chemical reactivities.[9]
POMs has been extensively studied because they have many practical applications in
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
catalysis,[10,11] molecular materials,[12] and corrosion inhibition.[13] In recent decades, uses of
some POMs as catalysts for fine organic synthetic processes have been developed and are
important for industries related with fine chemicals,[14] including flavors, pharmaceuticals and
food industries.[15] In recent years, the synthesis of nanotubular materials consisting of POMs
such as POMs-including titania nanotubes[16] and POMs-organic hybrid nanotubes[17] have been
a subject of increasing interest. These new types of nanotubes show both the functional
properties of POMs but also the advantages of tubular systems in the application, for example, of
catalytic and photochemical properties. [16-18] Müller and co-workers, for the first time, reported
the famous remarkable giant nanosized porous Keplerate type POM.[19] The Keplerate and giant
nanosized porous polyoxometalates show unique features which can be considered as the basis
of a new type of nanochemistry and nanomaterials science.[20,21] They find a large variety of
applications in fundamental and applied science, such as in modelling passive cation transport
through membranes, encapsulation, nanoseparation chemistry, magnetic and optics
properties.[22,23] In spite of these valuable properties, to the best of our knowledge, there is only
one reference in the literature on the use of giant nanosized porous polyoxometalates as catalyst
in epoxidation of olefins[24] and there is no report on the use of them as catalyst in MCRs.
The 1,4-dihydropyridine (1,4-DHP) core is found in a range of compounds exhibiting a
broad spectrum of biological activities.[25,26] Some of the representative compounds of this class
possess antimicrobial,[27] antitubercular,[28] insecticidal,[29] and neuroprotectant[30] activities.
Particularly, 4-aryl-1,4-DHPs are well known as calcium channel blockers and have emerged as
one of the most important class of drugs for the treatment of cardiovascular diseases.[31,32]
Polyhydroquinolines are a class of fused 1,4-DHPs which have received less attention than other
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
fused 1,4-DHPs and comparatively very few methods for their preparation have been reported.
Polyhydroquinolines are generally synthesized by unsymmetrical Hantzsch reaction which
involves the one-pot four-component condensation of dimedone, aldehydes, ammonium acetate,
and ethyl acetoacetate using a catalyst such as montmorillonite K-10,[33] Nafion-H,[34] L-
proline,[35] vanadium dodecylamino phosphate,[36] trifluoroethanol,[37] FeF3,[38] Yb(OTf)3,[39]
K7[PW11CoO40],[40] TiO2 nanoparticles,[41] and [TBA]2[W6O19].[42] Synthesis of these compounds
using microwave irradiation,[43,44] solar thermal energy,[45] and grinding[46] have also been
reported. Nevertheless, in most of these methodologies, the reaction times are long. Also,
unsatisfactory yields and tedious isolation procedures are some disadvantages in some of them.
These finding make further improvements for the synthesis of these compounds essential.
Due to our interest in the synthesis of heterocyclic compounds,[47-50] and as part of our
research on the development of environmentally friendly methods for the synthesis of organic
compounds using reusable catalysts,[51-54] we report here the application of a Keplerate type giant
nanoporous isopolyoxomolybdate, (NH4)42[MoVI72MoV60O372(CH3COO)30(H2O)72], denoted as
({Mo132}) (Figure 1), as highly efficient and reusable novel catalyst to promote the synthesis of
polyhydroquinoline derivatives by a one-pot, four-component Hantszch condensation of
dimedone, an aldehyde, ammonium acetate, and ethyl acetoacetate under solvent-free conditions
(Scheme 1). The diameter of this ball-shaped POM which calculated theoretically is 2.9 nm.[19,20]
For the first time this molybdenum cluster has been characterized by the TEM image by Polarz
et.al.[21] The TEM picture clearly shows a periodic structure with an average size approximately
3 nm diameter. This experimentally obtained diameter fits nicely with the theoretical value for
the inner diameter of the ball-shaped POM. [19,20]
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
EXPERIMENTAL
Chemicals and Apparatus
All chemicals were available commercially and used without additional purification. The
catalyst was synthesized according to the literature. Melting points were recorded on a Stuart
SMP3 melting point apparatus. The IR spectra were obtained using a Tensor 27 Bruker
1
spectrophotometer as KBr disks. The H NMR (400 and 500 MHz) spectra were recorded with
Bruker 400 and 500 spectrometers.
Synthesis of the Keplerate {Mo132}
N2H4.H2SO4 (0.8 g, 6.1 mmol) was added to a solution of (NH4)6Mo7O24.4H2O (5.6 g, 4.5
mmol) and CH3COONH4 (12.5 g, 162.2 mmol) in H2O (250 ml). The solution was then stirred
for 10 min (color change to bluegreen) and 50% CH3COOH (83 ml) was subsequently added.
The reaction solution, now green, was stored in an open 500-ml Erlenmeyer flask at 20°C
without further stirring (slow color change to dark brown). After 4 d the precipitated red-brown
crystals were filtered off, washed with absolute ethanol and diethyl ether, respectively, and
finally dried in air.[19]
General Procedure for the Synthesis of Polyhydroquinolines 5a-k catalyzed by
{Mo132}
A mixture of dimedone 1 (1 mmol), an aldehyde 2a-k (1 mmol), ammonium acetate 3 (1
mmol), ethyl acetoacetate 4 (1 mmol) and {Mo132} (0.08 g) was heated in an oil bath at 120°C
for a few seconds or (for some cases) minutes. The reaction was monitored by TLC. Upon
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
completion of the transformation, the reaction mixture was cooled to room temperature and hot
ethanol was added. This resulted in the precipitation of the catalyst, which was collected by
filtration. The catalyst was washed with a small portion of hot ethanol (5 ml). The combined
filtrate was concentrated by half and allowed to stand at r.t.. The precipitated solid was collected
by filtration, and recrystallized from ethanol to give compounds 5a-k in high yields.
1H NMR & FT-IR data:
Ethyl 2,7,7-trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
(5a)
1H NMR (500 MHz, CDCl3):  0.96 (s, 3H, CH3), 1.10 (s, 3H, CH3), 1.22 (t, 3H, J = 7.1
Hz, CH3), 2.16-2.39 (m, 4H, 2CH2), 2.41 (s, 3H, CH3), 4.08 (q, 2H, J = 7.1 Hz, OCH2), 5.09 (s,
1H, CH), 6.18 (s br., 1H, NH), 7.13 (t, 1H, J = 7.3 Hz, arom-H), 7.22 (t, 2H, J = 7.5 Hz, arom-
H), 7.33 (d, 2H, J = 7.7 Hz, arom-H); IR (KBr, cm1): υ 3290, 3082, 2957, 1699, 1641, 1611,
1485, 1382, 1215, 1072, 699.
Ethyl
4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5b)
1H NMR (400 MHz, CDCl3):  0.94 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.21 (t, 3H, J = 7.2
Hz, CH3), 2.13-2.38 (m, 4H, 2CH2), 2.40 (s, 3H, CH3), 4.07 (q, 2H, J = 7.2 Hz, OCH2), 5.03 (s,
1H, CH), 5.95 (s br., 1H, NH), 7.20 (d, J = 8.4 Hz, 2H, arom-H), 7.33 (d, J = 8.4 Hz, 2H, arom-
H); IR (KBr, cm1): υ 3276, 3206, 3075, 2925, 1703, 1648, 1604, 1491, 1381, 1280, 1215, 1072.
Ethyl
4-(2-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
carboxylate (5c)
1H NMR (400 MHz, CDCl3):  0.96 (s, 3H, CH3), 1.08 (s, 3H, CH3), 1.19 (t, 3H, J = 6.8
Hz, CH3), 2.10-2.35 (m, 4H, 2CH2), 2.32 (s, 3H, CH3), 4.05 (q, 2H, J = 6.8 Hz, OCH2), 5.40 (s,
1H, CH), 6.14 (s br., 1H, NH), 7.04 (t, J = 7.2 Hz, 1H, arom-H), 7.13 (t, J = 7.2 Hz, 1H, arom-
H), 7.25 (d, J = 8.0 Hz, 1H, arom-H), 7.40 (d, J = 7.2 Hz, 1H, arom-H); IR (KBr, cm1): υ 3290,
3209, 3080, 2959, 1699, 1610, 1493, 1380, 1281, 1217, 1074, 755.
Ethyl
4-(4-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5d)
1H NMR (400 MHz, CDCl3):  0.95 (s, 3H, CH3), 1.10 (s, 3H, CH3), 1.21 (t, 3H, J = 7.2
Hz, CH3), 2.15-2.38 (m, 4H, 2CH2), 2.40 (s, 3H, CH3), 4.07 (q, 2H, J = 7.2 Hz, OCH2), 5.04 (s,
1H, CH), 6.08 (s br., 1H, NH), 7.18 (d, J = 8.4 Hz, 2H, arom-H), 7.26 (d, J = 8.4 Hz, 2H, arom-
H); IR (KBr, cm1): υ 3275, 3192, 3076, 2959, 1706, 1649, 1604, 1489, 1382, 1280, 1214, 1071.
Ethyl 4-(3-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5e)
1H NMR (400 MHz, DMSO-d6):  0.87 (s, 3H, CH3), 1.01 (s, 3H, CH3), 1.15 (t, 3H, J =
6.8 Hz, CH3), 1.98 (d, J = 16.4 Hz, 1H, one proton of diastereotopic protons in CH2), 2.16 (d, J =
16.4 Hz, 1H, one proton of diastereotopic protons in CH2), 2.28 (d, J = 16.8 Hz, 1H, one proton
of diastereotopic protons in CH2), 2.27 (s, 3H, CH3), 2.40 (d, J = 16.8 Hz, 1H, one proton of
diastereotopic protons in CH2), 3.98 (q, 2H, J = 6.8 Hz, OCH2), 4.78 (s, 1H, CH), 6.43-6.61 (m,
3H, arom-H), 6.95 (t, J = 8.0 Hz, 1H, arom-H), 9.03 (s br., 1H, NH or OH), 9.10 (s br., 1H, NH
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
or OH),; IR (KBr, cm1): υ 3291, 3079, 2959, 1677, 1609, 1485, 1380, 1278, 1217, 1074.
Ethyl 4-(4-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5f): 1H NMR (400 MHz, DMSO-d6):  0.85 (s, 3H, CH3), 1.00 (s, 3H, CH3), 1.13
(t, 3H, J = 7.2 Hz, CH3), 1.96 (d, J = 16.8 Hz, 1H, one proton of diastereotopic protons in CH2),
2.15 (d, J = 16.8 Hz, 1H, one proton of diastereotopic protons in CH2), 2.25 (s, 3H, CH3), 2.27
(d, J = 17.2 Hz, 1H, one proton of diastereotopic protons in CH2), 2.40 (d, J = 17.2 Hz, 1H, one
proton of diastereotopic protons in CH2), 3.96 (q, 2H, J = 7.2 Hz, OCH2), 4.73 (s, 1H, CH), 6.55
(d, J = 8.4 Hz, 2H, arom-H), 6.92 (d, J = 8.4 Hz, 2H, arom-H), 8.98 (s br., 1H, NH or OH), 9.06
(s br., 1H, NH or OH); IR (KBr, cm1): υ 3416, 3280, 3207, 3076, 2959, 1687, 1612, 1486, 1380,
1271, 1220.
Ethyl
4-(3-nitrophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5g)
1H NMR (400 MHz, CDCl3):  0.95 (s, 3H, CH3), 1.11 (s, 3H, CH3), 1.21 (t, 3H, J = 7.2
Hz, CH3), 2.13-2.39 (m, 4H, 2CH2), 2.41 (s, 3H, CH3), 4.07 (q, 2H, J = 7.2 Hz, OCH2), 5.17 (s,
1H, CH), 6.23 (s br., 1H, NH), 7.39 (t, J = 8.0 Hz, 1H, arom-H), 7.74 (d, J = 7.6 Hz, 1H, arom-
H), 7.97-8.02 (m, 1H, arom-H), 8.13 (t, J = 2.0 Hz, 1H, arom-H); IR (KBr, cm1): υ 3283, 3211,
3076, 2958, 1704, 1606, 1534, 1487, 1380, 1352, 1280, 1211, 1071.
Ethyl
4-(4-nitrophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5h)
1H NMR (400 MHz, CDCl3):  0.94 (s, 3H, CH3), 1.12 (s, 3H, CH3), 1.20 (t, 3H, J = 7.1 Hz,
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
CH3), 2.15-2.43 (m, 4H, 2CH2), 2.45 (s, 3H, CH3), 4.08 (q, 2H, J = 7.1 Hz, OCH2), 5.19 (s, 1H,
CH), 6.00 (s br., 1H, NH), 7.51 (d, J = 8.5 Hz, 2H, arom-H), 8.11 (d, J = 8.5 Hz, 2H, arom-H);
IR (KBr, cm1): υ 3275, 3189, 3074, 2966, 1703, 1649, 1607, 1518, 1493, 1378, 1344, 1280,
1215, 1072.
Ethyl
4-(4-methylphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5i)
1H NMR (400 MHz, CDCl3):  0.96 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.24 (t, 3H, J = 7.2
Hz, CH3), 2.14-2.35 (m, 4H, 2CH2), 2.28 (s, 3H, CH3), 2.36 (s, 3H, CH3), 4.09 (q, 2H, J = 7.2
Hz, OCH2), 5.03 (s, 1H, CH), 6.41 (s br., 1H, NH), 7.02 (d, J = 7.6 Hz, 2H, arom-H), 7.21 (d, J =
7.6 Hz, 2H, arom-H); IR (KBr, cm1): υ 3276, 3207, 3077, 2959, 1702, 1605, 1494, 1380, 1281,
1216, 1072.
Ethyl 4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5j)
1H NMR (400 MHz, CDCl3):  0.96 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.23 (t, 3H, J = 7.2
Hz, CH3), 2.15-2.36 (m, 4H, 2CH2), 2.38 (s, 3H, CH3), 3.75 (s, 3H, OCH3), 4.09 (q, 2H, J = 7.2
Hz, OCH2), 5.02 (s, 1H, CH), 6.27 (s br., 1H, NH), 6.75 (d, J = 8.8 Hz, 2H, arom-H), 7.23 (d, J =
8.8 Hz, 2H, arom-H); IR (KBr, cm1): υ 3276, 3206, 3077, 2957, 1702, 1649, 1605, 1496, 1380,
1280, 1215, 1072.
Ethyl 2,7,7-trimethyl-5-oxo-4-propyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
(5k)
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1H NMR (400 MHz, CDCl3):  0.84 (t, 3H, J = 7.2 Hz, CH3), 1.10 (s, 6H, 2CH3), 1.15-
1.27 (m, 2H, CH2), 1.30 (t, 3H, J = 7.2 Hz, CH3), 1.30-1.43 (m, 2H, CH2), 2.17-2.37 (m, 4H,
2CH2), 2.32 (s, 3H, CH3), 4.03 (t, 1H, J = 5.2 Hz, CH), 4.10-4.25 (m, 2H, OCH2), 6.09 (s br.,
1H, NH); IR (KBr, cm1): υ 3277, 3210, 2958, 1699, 1639, 1601, 1489, 1393, 1279, 1216, 1066.
RESULTS AND DISCUSSION
Characterization of the Catalyst
The {Mo132} catalyst was characterized by FT-IR and UV/Vis spectroscopy. The FT-IR
spectrum of the catalyst shown in Figure 3a exhibits the characteristic vibrational bonds of Mo =
+
O at 969 and 936, the COO and NH4 at 1544 & 1407 as well as H2O at 2500-3600 & 1618. The
locations of these featured peaks for the prepared catalyst as well as other bonds at 855, 792,
725, 628, 568, 514 and 467 were in well agreement with those reported by Müller[19] and
Zhou.[20] The UV/Vis spectrum also confirms the structure of the prepared catalyst indicating the
characteristic absorption bonds at 213, 232, 265, and 447 nm which are in agreement with
literature.[19]
Catalytic Performance of {Mo132} in the Synthesis of Polyhydroquinolines
In order to evaluate the catalytic efficiency of {Mo132} in the synthesis of
polyhydroquinolines and to determine the most appropriate reaction conditions; initially a model
study was carried out on the synthesis of compound 5d by reaction of dimedone 1 (1 mmol), 4-
chlorobenzaldehyde 2d (1 mmol), ammonium acetate 3 (1 mmol), and ethyl acetoacetate 4 (1
mmol) in different sets of reaction conditions (Table 1). As can be seen from Table 1, among the
10
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
tested solvents such as EtOH, MeOH, H2O, CH2Cl2, CH3CN, and also solvent-free conditions
and various amounts of the catalyst, the shortest time and best yield was achieved in solvent-free
conditions. It was also found that the yield of compound 5d was strongly affected by the catalyst
amount and reaction temperature in solvent-free conditions. No product was obtained in the
absence of the catalyst at 120°C following a 60 min reaction time (entry 1) indicating that the
catalyst is necessary for the reaction. Increasing the amount of the catalyst and reaction
temperature up to 0.08 g and 120°C, respectively, increased the yield of the product 5d, whereas
further increase in both catalyst amount and temperature did not improve the product yield and
reaction time.
With optimized conditions in hand, and in order to evaluate the scope of this catalytic
transformation, a range of polyhydroquinolines were prepared by the reaction of dimedone,
various aldehydes, ammonium acetate, and ethyl acetoacetate. The results are summarized in
Table 2. In most cases, the reactions are terminated after a few seconds and for some cases in a
few minutes, giving the products 5a-k in high yields. On the other hand, easy separation of
obtained products from the catalyst makes this method useful for the synthesis of
polyhydroquinolines.
To further evaluate the overall utility of the current methodology, we compared our
results with those of the other methods reported for the synthesis of polyhydroquinolines (Table
3). Our reaction conditions showed a shorter reaction time than all the other conditions and gave
high yields of the desired products.
11
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
The reusability of {Mo132} was also investigated. For this purpose, the synthesis of
compound 5d was again studied under optimized conditions. The {Mo132} catalyst was readily
recovered from the reaction mixture using the procedure outlined in the experimental section.
The separated catalyst was washed with hot ethanol and then dried at 60°C under vacuum for 1 h
before being reused in a similar reaction. We found that the catalyst could be reused at least four
times with only a slight reduction in activity (Figure 2). Furthermore, the FT-IR spectra of the
recovered catalysts were almost identical to the spectrum of the fresh catalyst, indicating that the
structure of the catalyst was unchanged by the reaction (Figure 3).
At the end, since the {Mo132} catalyst has several accessible Mo sites which can act as
Lewis acid centers, we therefore believe that it promotes these reactions by increasing the
electrophilic character of the carbonyl groups in the reactions.
CONCLUSION
In conclusion, we showed that {Mo132}, a Keplerate type giant nanoporous
isopolyoxomolybdate, efficiently catalyzes the synthesis of polyhydroquinolines via one-pot
four-component unsymmetrical Hantzsch condensation of dimedone, aromatic or aliphatic
aldehydes, ammonium acetate, and ethyl acetoacetate. The method was very fast and the desired
products were obtained within a few seconds or minutes (for some cases) in high yields under
solvent-free conditions at 120 ºC. The catalyst can be recycled after a simple work-up, and
reused at least four times without substantial reduction in its catalytic activity. The procedure is
also advantageous in the sense that it is a solvent-free reaction and therefore operates under
environmentally friendly conditions.
12
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Acknowledgement
The authors express their gratitude to the Islamic Azad University, Mashhad Branch for its
financial support.
13
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
REFERENCES
1. Trost, B. M. Science 1991, 254, 1471.
2. Jalde, S. S.; Chavan, H. V.; Adsul, L. K.; Dhakane, V. D.; Bandgar, B. P. Synth. React.
Inorg. Met.-Org. Nano-Met. Chem. 2014, 44, 623.
3. Davoodnia, A.; Norouzi, H.; Tavakoli-Hoseini, N.; Zare-Bidaki, A. Synth. React. Inorg.
Met.-Org. Nano-Met. Chem. 2014, 44, 70.
4. Domling, A. Chem. Rev. 2006, 106, 17.
5. Mobinikhaledi, A.; Foroughifar, N.; Karimi, G.; Forougifar, N. Synth. React. Inorg. Met.-
Org. Nano-Met. Chem. 2007, 37, 279.
6. Mohammadzadeh-Dehsorkh, N.; Davoodnia, A.; Tavakoli-Hoseini, N.; Moghaddas, M.
Synth. React. Inorg. Met.-Org. Nano-Met. Chem. 2011, 41, 1135.
7. Toure B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439.
8. Okuhara, T. Chem. Rev. 2002, 102, 3641.
9. Pope, M. T. Heteropoly and Isopoly Oxometalates; Springer- Verlag: Berlin, 1983.
10. Mizuno, N.; Misono, M. Chem. Rev. 1998, 98, 199.
11. Sadakane, M.; Steckhan, E. Chem. Rev. 1998, 98, 219.
12. Coronado, E.; Gomez-Garcia, C. J. Chem. Rev. 1998, 98, 273.
14
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
13. Katsoulis, D. E. Chem. Rev. 1998, 98, 359.
14. Kozhevnikov, I. V. in: E. Derouane (Ed.), Catalysts for Fine Chemical Synthesis, Catalysis
by Polyoxometalates 2, Wiley, New York, 2002.
15. Okuhara, T.; Mizuno, N.; Misono, M. Adv. Catal. 1996, 41, 113.
16. Xie, Y. Adv. Funct. Mater. 2006, 16, 1823.
17. Ma, Z.; Liu, Q.; Cui, Z.; Bian, S.; Song, S. J. Phys. Chem. C 2008, 112, 8875.
18. Zhang, Y.; Li, D.; Chen, Y.; Wang, X.; Wang, S. Appl. Catal. B 2009, 86, 182.
19. Muller, A.; Krickemeyer, E.; Bögge, H.; Schmidtmann, M.; Peters, F. Angew. Chem. Int. Ed.
1998, 37, 3359.
20. Zhang, L.; Xiong, T.; Zhou, Y.; Zhang, L. Chem. Asian J. 2010, 5, 1984.
21. Polarz, S.; Smarsly, B.; Gçltner, C.; Antonietti, M. Adv. Mater. 2000, 12, 1503.
22. Muller, A.; Das, S K.; Talismanov, S.; Roy, S.; Beckmann, E.; Bçgge, H.; Schmidtmann, M.;
Merca, A.; Berkle, A.; Allouche, L.; Zhou, Y.; Zhang, L. Angew. Chem. Int. Ed. 2003, 42,
5039.
23. Greedan, J. Mater. Chem. 2001, 11, 37.
24. Rezaeifard, A.; Haddad, R.; Jafarpour, M.; Hakimi, M. J. Am. Chem. Soc. 2013, 135, 10036.
25. Carosati, E.; Ioan, P.; Micucci, M.; Broccatelli, F.; Cruciani, G.; Zhorov, B. S.; Chiarini, A.;
Budriesi, R. Curr. Med. Chem. 2012, 19, 4306.
15
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
26. Vo, D.; Matowe, W. C.; Ramesh, M.; Iqbal, N.; Wolowyk, M. W.; Howlett, S. E.; Knaus, E.
E. J. Med. Chem. 1995, 38, 2851.
27. Murthy, Y. L. N.; Rajack, A.; Taraka Ramji, M.; Jeson Babu, J.; Praveen, C.; Aruna
Lakshmi, K. Bioorg. Med. Chem. Lett. 2012, 22, 6016.
28. Trivedi, A.; Dodiya, D.; Dholariya, B.; Kataria, V.; Bhuva, V.; Shah, V. Chem. Biol. Drug
Des. 2011, 78, 881.
29. Sun, C.; Chen, Y.; Liu, T.; Wu, Y.; Fang, T.; Wang, J.; Xing, J. Chin. J. Chem. 2012, 30,
1415.
30. Klusa, V. Drugs Fut. 1995, 20, 135.
31. Miyashita, K.; Nishimoto, M.; Ishino, T.; Obika, S.; Imanishi, T. Chem. Pharm. Bull. 1995,
43, 711.
32. Bossert, F.; Meyer, H.; Wehinger, E. Angew. Chem. Int. Ed. 1981, 20, 762.
33. Song, G.; Wang, B.; Wu, X.; Kang, Y.; Yang, L. Synth. Commun. 2005, 35, 2875.
34. Kidwai, M.; Chauhan, R.; Bhatnagar, D.; Singh, A. K.; Mishra, B.; Dey, S. Monatsh. Chem.
2012, 143, 1675.
35. Karade, N. N.; Budhewar, V. H.; Shinde, S. V.; Jadhav, W. N. Lett. Org. Chem. 2007, 4, 16.
36. Rajini, A.; Nookaraju, M.; Reddy, I. A. K.; Narayanan, V. Chem. Pap. 2014, 68, 170.
16
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
37. Heydari, A.; Khaksar, S.; Tajbakhsh, M.; Bijanzadeh, H. R. J. Fluorine Chem. 2009, 130,
609.
38. Surasani, R.; Kalita, D.; Dhanunjaya Rao, A. V.; Yarbagi, K.; Chandrasekhar, K. B. J.
Fluorine Chem. 2012, 135, 91.
39. Wang, L. M.; Sheng, J.; Zhang, L.; Han, J. W.; Fan, Z. Y.; Tian, H.; Qian, C. T. Tetrahedron
2005, 61, 1539.
40. Heravi, M. M.; Bakhtiari, K.; Javadi, N. M.; Bamoharram, F. F.; Saeedi, M.; Oskooie, H. A.
J. Mol. Catal. A: Chem. 2007, 264, 50.
41. Tajbakhsh, M.; Alaee, E.; Alinezhad, H.; Khanian, M.; Jahani, F.; Khaksar, S.; Rezaee, P.;
Tajbakhsh, M. Chin. J. Catal. 2012, 33, 1517.
42. Davoodnia, A.; Khashi, M.; Tavakoli-Hoseini, N. Chin. J. Catal. 2013, 34, 1173.
43. Sapkal, S. B.; Shelke, K. F.; Shingate, B. B.; Shingare, M. Tetrahedron Lett. 2009, 50, 1754.
44 Tu, S. J.; Zhou, J. F.; Deng, X.; Cai, P. J.; Wang, H.; Feng, J. C. Chin. J. Org. Chem. 2001,
21, 313.
45. Mekheimer, R. A.; Hameed, A. A.; Sadek, K. U. Green Chem. 2008, 10, 592.
46. Kumar, S.; Sharma, P; Kapoor, K. K.; Hundal, M. S. Tetrahedron 2008, 64, 536.
47. Davoodnia, A.; Bakavoli, M.; Pooryaghoobi, N.; Roshani, M. Heterocycl. Commun. 2007,
13, 323.
17
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
48. Davoodnia, A.; Roshani, M.; Saleh-Nadim, E.; Bakavoli, M.; Tavakoli-Hoseini, N. Chin.
Chem. Lett. 2007, 18, 1327.
49. Davoodnia, A.; Bakavoli, M; Bashash, M.; Roshani, M.; Zhiani, R. Turk. J. Chem. 2007, 31,
599.
50. Davoodnia, A.; Zhiani, R.; Tavakoli-Hoseini, N. Monatsh. Chem. 2008, 139, 1405.
51. Saburi, E.; Davoodnia, A.; Tavakoli-Hoseini, N. Synth. React. Inorg. Met.-Org. Nano-Met.
Chem. 2011, 41, 1063.
52. Davoodnia, A. Synth. React. Inorg. Met.-Org. Nano-Met. Chem. 2012, 42, 1022.
53. Davoodnia, A.; Zare-Bidaki, A.; Behmadi, H. Chin. J. Catal. 2012, 33, 1797.
54. Khoshnevis, M.; Davoodnia, A.; Zare-Bidaki, A.; Tavakoli-Hoseini N. Synth. React. Inorg.
Met.-Org. Nano-Met. Chem. 2013, 43, 1154.
18
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
TABLE 1 Optimization of reaction conditions for synthesis of compound 5d catalyzed by
{Mo132}
Isolated Yield
Entry
Catalyst (g)
Solvent
T (°C)
Time (min)
(%)
-----
73
1
-----
0.02
0.02
0.04
0.04
0.06
0.06
0.08
0.08
0.10
0.10
0.08
0.08
0.08
0.08
0.08
-----
-----
120
100
60
10
7
2
3
-----
120
78
4
-----
100
8
77
5
-----
120
5
83
6
-----
100
5
80
7
-----
120
2
89
8
-----
100
2
86
9
-----
120
<1
2
97
10
11
12
13
14
15
16
-----
100
92
-----
120
<1
60
60
60
70
70
96
EtOH
MeOH
H2O
Reflux
Reflux
Reflux
Reflux
Reflux
25
19
32
CH2Cl2
CH3CN
trace
trace
Reaction conditions: dimedone 1 (1 mmol), 4-chlorobenzaldehyde 2d (1 mmol), ammonium
acetate 3 (1 mmol), and ethyl acetoacetate 4 (1 mmol)
19
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
TABLE 2 {Mo132} catalyzed synthesis of polyhydroquinolines 5a-k
m.p. (ºC)
Entr
y
Time
(min)
Isolated
Yields (%)
R
Products
Found
Reported
202-205
[35]
1
<1
95
210-212
5a
251-253
[35]
2
<1
94
250-253
5b
206-208
[42]
3
<1
20
92
205-207
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
5c
246-248
[42]
4
<1
97
245-247
5d
225-227
[42]
5
2
90
220-223
5e
6
1
91
237-240
234-237
21
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
[35]
5f
176-179
[35]
7
<1
95
179-181
5g
241-243
[35]
8
<1
91
243-245
22
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
5h
260-261
[39]
9
<1
92
258-260
5i
252-254
[35]
10
<1
90
256-259
5j
147-148
[39]
11
3
90
148-150
23
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
5k
Reaction conditions: dimedone 1 (1 mmol), an aldehyde 2a-k (1 mmol), ammonium acetate 3 (1
mmol), ethyl acetoacetate 4 (1 mmol), {Mo132} (0.08 g), 120 ºC, solvent-free.
24
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
TABLE 3 Comparison of the efficiencies of different catalysts for the synthesis of
polyhydroquinolines
Conditions
Solvent
Isolated
Yield
(%)
Catalyst
Time (min)
Ref.
T (ºC)
reflux
montmorillonite K-10
Nafion-H
EtOH
20-100
90-100
360-420
34-95
88-96
81-92
[33]
[34]
[35]
PEG
400/H2O
50
L-Proline
EtOH
reflux
Vanadium
MeOH/H2O
r.t.
70
90-160
180
68-83
75-98
[36]
[37]
dodecylamino
phosphate
trifluoroethan
ol
trifluoroethanol
FeF3
EtOH
EtOH
CH3CN
EtOH
----
reflux
reflux
reflux
reflux
110
60-90
120-480
25-35
85-95
85-95
80-90
80-96
67-95
[38]
[39]
[40]
[41]
[42]
Yb(OTf)3
K7[PW11CoO40]
TiO2 nanoparticles
[TBA]2[W6O19]
25-45
20-40
This
work
{Mo132}
----
120
<1-3
90-97
25
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 1. Structure of {Mo132}
26
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 2. Reusability of {Mo132} for the synthesis of compound 5d.
27
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 3. FT-IR spectra of fresh catalyst {Mo132} (a, first run), and recovered catalysts (b-e,
second to fifth run, respectively) for synthesis of compound 5d in model reaction.
28
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Scheme 1. Synthesis of polyhydroquinolines catalyzed by {Mo132}
29
ACCEPTED MANUSCRIPT