Keggin type phosphotungstic acid encapsulated chromium (III) terephthalate metal organic framework as active catalyst for Biginelli condensation

Article abstract of DOI:10.1016/j.apcata.2015.05.021

Keggin-type phosphotungstic acid (H₃PW₁₂O₄₀, PTA) encapsulated in the mesocages of chromium-based terephthalate metal-organic framework (MIL-101) was established to be an active heterogeneous catalyst for three component B

Full text of DOI:10.1016/j.apcata.2015.05.021

Accepted Manuscript
Title: Keggin type phosphotungstic acid encapsulated
Chromium (III) Terephthalate Metal Organic Framework as
active catalyst for Biginelli condensation
Author: Mrinal Saikia Diganta Bhuyan Lakshi Saikia
PII:
S0926-860X(15)00326-9
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2015.05.021
APCATA 15395
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
7-3-2015
9-5-2015
16-5-2015
Please cite this article as: M. Saikia, D. Bhuyan, L. Saikia, Keggin type phosphotungstic
acid encapsulated Chromium (III) Terephthalate Metal Organic Framework as
active catalyst for Biginelli condensation, Applied Catalysis A, General (2015),
http://dx.doi.org/10.1016/j.apcata.2015.05.021
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Highlights:
 The Biginelli reaction was studied.
 Heteropoly acid H3PW12O40 (PW) encapsulated into MIL101 was used as catalyst.
 Effect of MIL-101 on catalytic behaviour of PW was demonstrated.
 The catalyst is easily recoverable and reusable without much change in activity.
Page 1 of 18

Keggin type phosphotungstic acid encapsulated Chromium (III) Terephthalate Metal
Organic Framework as active catalyst for Biginelli condensation
Mrinal Saikiaa,b, Diganta Bhuyana, Lakshi Saikiaa,b*
aMaterials Science Division, CSIR-North East Institute of Science and Technology
Jorhat – 785006, Assam, India
bAcademy of Scientific and Innovative Research, New Delhi, India
*Corresponding author. Tel.: +91 376 2370 081; fax. +91 376 2370 011
*E-mail address: lakshi_saikia@yahoo.com
Abstract
Keggin- type phosphotungstic acid (H3PW12O40, PTA) encapsulated in the mesocages of
chromium-based terephthalate metal-organic framework (MIL-101) was established to be an
active heterogeneous catalyst for three component Biginelli condensation reaction with
excellent yields(75-90%) and selectivity under solvent free condition. Here phosphotungstic
acid can effectively incorporated into the matrix of MIL-101 by an impregnation method. The
synthesized PTA@MIL-101 was characterized by employing various spectroscopic
techniques as well as different analytical methods. Moreover, the catalyst could easily be
recovered and recycled without any significant loss of its catalytic activity.
Keywords: PTA@MIL-101; Impregnation, Biginelli condensation
1. Introduction
Nowadays multicomponent reaction has become a remarkable area of research,
particularly in organic chemistry [1] as these reactions surpass the atom economy of the
process. These reactions are key source of molecular diversity which makes them powerful
tool in modern drug discovery processes. Furthermore, the one-pot character furnishes fewer
by-products in comparison to classical stepwise synthetic route with lower cost, time and
energy. Among the multicomponent reactions, Biginelli reaction is one of the most studied
reactions since the product of this reaction is Dihydropyrimidinones (DHPMs) which are vital
medicinal synthones that display a wide range of biological activities such as antibacterial,
anti-inflammatory, antiviral, anti-tumour [2-4]. A large number of dihydropyrimidinones
derivatives are pharmacologically important as antagonists, antihypertensive agents,
significant calcium channel blockers, and neuropeptide antagonists [5-10]. Additionally,
several marine alkaloids involving the DHPM core unit, such as batzelladine alkaloids
possess certain biological properties which are of great significance.
Page 2 of 18

Various classical methods are available for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones
employing Lewis acids such as BF3·Et2O and Sr(NO3)2, ceric ammonium nitrate [11,12,13].
Heteropolyacids are also use as an acid catalyst for this transformation [14]. However, the
difficulties with polyoxometalates are their recovery and reuse in presence of water and
organic solvents [15,16]. To overwhelm this shortcoming, heterogenisation of these
polyoxometalates into various host supports like silica [17], activated carbon [18] and
zeolites [19] has already been reported. Nevertheless, these supported catalyst tend to have
restricted POM loading, show some leaching and susceptible for agglomeration [20].
MIL-101(Materials of the Institut Lavoisier no. 101) is mesoporous metal-organic
framework, has mesosize cages of 2.9 and 3.4 nm with two microporous windows of 1.2 and
1.6 nm respectively[21-22], resulting a high surface area that make this MOF an attractive
host for the encapsulation of polyoxometalates. Moreover, supporting phosphotungstic acid
in the host lattice structure of metal-organic framework provide many advantages like
improving the molecular accessibility by isolating the individual keggin units as compared to
its bulk counterpart which has relatively low surface area(<10 m2g-1), facile catalyst recovery
and recycling etc. Several attempts have been made for encapsulating polyoxometalates into
the matrix of metal-organic framework [23-34]. These phosphotungstic acids encapsulated
into MIL-101 exhibits good catalytic performance in the esterification reaction of n-butanol
with acetic acid in the liquid phase [24], Knoevenagel condensation [24], oxidative
desulfurization[29], selective oxidation of alkenes with aqueous hydrogen peroxide[30],
hydrolysis and esterification reaction [33], selective dehydration of fructose and glucose to 5-
hydroxymethylfurfural [34], aldehyde-alcohol reactions [36], etc. Like MIL-101,
Cu3(BTC)2(HKUST-1) is also a potential metal-organic framework for successful
incorporation of keggin type phosphotungstic acids. L.H. Wee and his co-workers
synthesized Cu3(BTC)2 encapsulated Keggin heteropolyacid nanomaterial and investigate its
catalytic activity in acid catalyzed esterification reaction [23] [32]. Micek-Ilnicka et al.
synthesized a hybrid material of tungsten heteropolyacid (HPW) and iron-based MOF Basolite™ F
300 and demonstrate the influence of acid particles distribution on ethanol conversion in hybrid
materials [27]. Keeping that in mind, we have synthesized a hybrid material of
phosphotungstic acid with MIL-101 through an impregnation technique [37] and studied its
catalytic activity in Biginelli reaction under solvent free condition. The catalyst is easily
recoverable and reused up to three times without significant loss of its activity. Hence, short
Page 3 of 18

reaction time, facile recovery and recycling of the catalyst and solvent free condition makes
our process more advantageous to that of the other processes.
2. Experimental
2.1 Synthesis of MIL-101
MIL-101 was prepared according to the reported method by Férey et al[1]. involving
hydrothermal treatment of a mixture of 3mmol of Cr(NO3)3·9H2O, 3mmol of terephthalic
acid (H2bdc) and 0.6ml of 5M HF (3mmol) in 15ml H2O at 2200C for 8h in a Teflon-lined
autoclave bomb. After equilibration at ambient temperature, the resulting Cr-MIL-101 solid
was filtered to remove the unreacted colourless crystals of H2bdc and purified by double
treatment with DMF at 600C for 3h and then triple treatment with ethanol at 700C for 2.5h.
Finally the green solid was separated by centrifugation, dried in an air oven at 700C overnight
and kept it in a vacuum desiccator.
2.2 Synthesis of PTA@MIL-101
1 g of dry MIL-101 was added to an aqueous solution of phosphotungstic acid (0.6g
dissolved in 20ml of distilled water). The resulting suspension was sonicated and stirring at
room temperature for 48h. The solids were separated by centrifugation, repeatedly washed by
methanol and water and dried under vacuum. The W content (10wt %) in the synthesized
material has been calculated from AAS technique.
2.3 General procedure for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones
A solution of ethylacetoacetate (1 mmol), aldehyde (1 mmol) and urea (1.5 mmol)
was heated to 1000 C under solvent-free condition in the presence of PTA@MIL-101 (0.6
mol%). The progress of the reaction was monitored through TLC. After completion, the
reaction mixture was cooled to room temperature, dissolved in ethanol and filtered to separate
the catalyst. The ethanol was evaporated in rotavapor and the crude product was poured into
crushed ice with thorough stirring for 10 min. The solid product was filtered and further
purified by re-crystallization from n-hexane/ethyl acetate(3:1), to afford pure 3,4-
dihydropyrimidin -2(1H)-ones. The products were characterized by (1H, 13C) NMR
spectroscopy and all give satisfactory results (ESI).
3. Results and Discussion
Metal-organic framework like MIL-101 is a robust material with mesoporous cages
that possesses high surface area as well as high hydrothermal stability. These features make
this MOF a good candidate as catalyst support [38] for various important organic
transformations. The MOF is synthesized by following the reported method by Férey et al.
Page 4 of 18

and phosphotungsic acid was incorporated in its matrix by a simple impregnation method.
The resulting PTA@MIL-101 was thoroughly characterized with the help of different
analytical techniques like PXRD, FT-IR, N2 physisorption, 31P Solid state MAS NMR, NH3-
TPD, XPS and FESEM analysis. The PXRD pattern of the composite PTA@MIL-101
possesses notable changes in the diffraction patterns after incorporation of PTA in MIL-101.
Characteristic diffraction peaks appears between 2(6-8o) of the composite materials (Fig
1(b)) in comparison to the parent material (Fig 1(a)) clearly demonstrated the ordered
assembly of PTA molecules into the cages of MIL-101 [23]. This ordered encapsulation of
heteropoly acid increases the stability of MIL-101 as indicated by the thermogravimetric
study (ESI, Fig S2). However, no reflection peak characteristic of bulk PTA is observed,
establishing the well dispersion of PTA molecules in the mesocages of MIL-101.
The FESEM images of MIL-101 and PTA@MIL-101 is shown in (ESI, Fig.S3 (a),
(b)). It is seen that phosphotungstic acid incorporates on MIL-101 surface without
fragmenting the characteristic cubic symmetry of parent MIL-101. TEM images of the
composites (ESI, Fig S4) retained the overall octahedral shape of the autoclaved MIL-101
particles although the shape was slightly less well defined, because of the extended exposure
of the MIL-101 to water in the process of impregnation. The elemental mapping (Fig.2) of
different elements clearly demonstrate the well distribution of phosphotungstic acid in the
mesocages of MIL-101.
The specific surface area of the composite material was measured by N2 physisorption
analysis at 77K (Fig.4(a)). The BET surface area and pore volume of PTA@MIL-101 was
found to be lower than that of the pristine MIL -101 which is supposed to be filling of the
pore space of the support by the heavy heteropolyacid molecules. In spite of that, significant
BET surface area and pore volume of 1032 m2g-1 and 0.61cm3g-1 were retained. The
differential pore volume versus pore diameter plot, i.e. BJH plot, (ESI, Fig.S5) shows the
uniform pore distribution of the support after encapsulation of the heteropoly acid molecules.
FT-IR analysis of the composite material (Fig. 3(b)) shows the characteristic bands at 828,
903 ν(W-O-W), 983 ν(W=O) and 1080 cm-1 ν(P-O), confirming the incorporation of Keggin
HPW in MIL-101[38,39]. The 31P solid-state MAS NMR (Fig.3(c)) exhibit a single signal at -
15.4 ppm which clearly indicates the stability of Keggin polyoxometal anion within the cages
of MIL-101. XPS spectrum of PTA@MIL-101 reveals the presence of phosphotungstic acid
within the framework of MIL-101(ESI, Fig. S1)
Page 5 of 18

The acidity of the PTA@MIL-101 has measured through Temperature- programmed
desorption (TPD) of ammonia. In the NH3-TPD profile (ESI, Fig S6) the desorption peak
positioned at low temperature 233oC can be designated to NH3 adsorbed on the open metal
sites of MIL-101 [39]. The signal appeared at higher temperature (667oC) may be attributed
to the ammonium salt of heteropoly acids [40]. The position of the peak at higher temperature
is shifted as compared to that of the neat phosphotungstic acid may be owing to the
incorporation of phosphotungstic acid to the matrix of the parent MOF [38]. The total amount
of acidic sites on the synthesized PTA@MIL-101 as determined from the NH3-TPD was
found to be 0.288 mmol g-1.
The condensation reaction between aldehydes, 1,3-dicarbonyl compounds and urea or
thiourea catalyzed by phosphotungstic acid, an environmentally benign solid protic acid
under solvent free condition is an important organic transformation as the products of the
reaction are of biological importance. In our present protocol, the three component
condensation reaction between benzaldehyde, ethylacetoacetate and urea was carried at
100oC using PTA@MIL-101 as catalyst under solvent free condition. This protocol gives
good yield of the products. The problems associated with using solvent such as cost, safety,
and handling are also examined. Furthermore, under solvent free condition, the reactivity
increases which results in the decrease of the reaction time. The use of the parent MIL-101
gave essentially no required product in this reaction system, confirming as anticipated the
need of phosphotungstic acid moiety to perform the condensation reaction. The incorporation
of phosphotungstic acid significantly enhances the reaction.
In order to monitor the catalytic efficiency of the heterogeneous PTA@MIL-101
catalytic system, we were carried out the same reaction in the presence of PTA@MIL-101
containing different PTA loading. Results of the reaction (Table.1) pointed to an optimized
performance of 0.6 mol% of PTA@MIL-101, which selectively furnish the corresponding
3,4-dihydropyrimidin-2(1H)-one in 90% yield at 100oC under solvent-free condition after 1h.
With increases in the amount of catalyst, i.e. for 0.9 mol% (Table.1, entry 4) resulted in the
declining of the product yield due to the internal diffusion limitations inside the porous
catalyst [41].
The potency of the reaction was influenced by temperature. Results of the reaction
between benzaldehyde, ethylacetoacetate and urea are summarized in (Table. 2). The yield of
the reaction was low below 80oC (Table. 2, entry 2) where increasing temperature from 90-
Page 6 of 18

130oC (Table.2, entry 3, 4) had insignificant effect on the yield%. Taking all these aspects
1000C temperature was selected for all the further studies.
The dimension of the presented catalyst system was then subsequently extended to the
different substituted aromatic aldehydes with electron withdrawing and electron releasing
substituents on the phenyl ring using the optimum PTA@MIL-101 catalyst. The results
summarized in (Table. 3), shows that PTA@MIL-101 was extremely active for all the
substrates of benzaldehydes including methylacetoacetate(Table. 3, entry 9, 10, 11, and 12)
and more importantly thiourea (Table. 3, entry 13, 14 and 15) that provide dihydropyrimidin-
2 (1H)-thiones which are of much concern relevant to biological activity indicating a high
flexibility of the MOF supported phosphotungstic acid catalyst.
The advantages of this present protocol over some reported methods were short
reaction time, solvent free reaction condition, catalyst recovery etc. From the catalysis point
of view we have selected the three component condensation reaction of urea,
ethylacetoacetate, and 4-nitrobenzaldehyde as a model reaction and make a comparison of
our results with that of the reported one (ESI, Table S1). Our catalyst is superior on the basis
of mol% of the catalyst as well as the time required for the chemical transformation.
A plausible mechanism (Scheme 1) was proposed based on available literature and
our experimental report. The reaction was proceed by imine formation from aldehyde and
urea or thiourea followed by the addition of enol tautomer of 1,3- dicarbonyl compounds to
the imine. The final step of the reaction is the cyclodehydration of ureide to afford the
corresponding dihydropyrimidin-2(1H)-one. Here PTA@MIL-101 acts as a proton source
which enhances the progress of the reaction by enolizing the 1,3-dicarbonyl compounds to
enolate intermediate and dehydrating the ureide. The support, due to its high surface area
provides not only better dispersion for the phosphotungstic acid, the active sites of the
reaction but also make a facile recovery of the catalyst from the reaction medium.
The heterogeneous nature of PTA@MIL-101 was confirmed by performing leachability
study of phosphotungstic acid from the support. A hot filtration test was carried out by taking
the reaction between ethylacetoacetate, benzaldehyde and urea as the model reaction (detail
procedure is in the supporting information). After 20 minute of the reaction the isolated
product yield was found to be 35%. No further increased in the yield beyond 40% is observed
after 60 minute of the reaction. The increase in the isolated product yield from 35% to 40%
may be due to the slight leaching of the phosphotungstic acid moiety from the support.
Page 7 of 18

For the interest of environmental friendly procedure, the reuse of the catalyst is more
desirable. The recyclability of the PTA@MIL-101 catalyst was examined in the condensation
of benzaldehyde, ethylacetoacetate and urea under the optimized conditions. After the
catalytic reaction, the catalyst was washed with ethanol, then with acetone, and dried at
1000C for 3h. The catalyst is then reutilized in subsequent runs under identical reaction
condition. The results included in the plot (Fig.4) shows that there was no loss in efficiency
of the catalyst up to three runs. FT-IR study of the recovered catalyst (Fig 3(b)) is also in
good agreement with this result. The peaks around 800-1100 cm-1 clearly established the
conservation of keggin structure of the heteropoly acid. The FESEM image of the recovered
catalyst (ESI, Fig S3 (C)) displays the preservation of the integrity of parent material. These
experimental results recommend that all the reactions are part of a heterogeneous process and
also reveal the robustness of the catalyst.
4. Conclusion
In summary, PTA encapsulated MIL-101 have been synthesized using the simple
impregnation approach. The obtained catalyst exhibited excellent activity for the solvent free
synthesis of various bioactive 3,4-dihydropyrimidin-2(1H)-ones through Biginelli reaction of
benzaldehyde, urea and ethylacetoacetate. Additionally, the catalyst is easily recoverable and
can be reused without notable change in its catalytic activity. The support makes an impact of
this catalytic transformation by heterogeneized heteropolyacids and facilitated the progress of
the reaction. Therefore, facile catalyst recovery, short reaction time as well as recyclability
established this heterogeneous catalyst as a potent candidate for this organic transformation
and making this methodology economically and environmentally acceptable.
Acknowledgements
The authors are grateful to the Director of CSIR-North East Institute of Science and
Technology, Jorhat, Assam, India for his kind permission to publish the work. We are
thankful to Dr P. Sengupta, Head of Materials Science Division and Dr D. K. Dutta for
support, and non network project MLP-6000(WP-1) and network project (CSC-0408) project
for financial assistance. M. S. acknowledges DST New Delhi for an INSPIRE fellowship.
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Captions
Fig. 1 (a) PXRD pattern of MIL-101, (b) PXRD pattern of PTA@MIL-101
Fig.2 EDS mapping of different elements of PTA@MIL-101
Fig.3 (a) N2 adsorption isotherm of PTA@MIL-101(red), MIL-101(black), (b) FT-IR spectra
of recovered PTA@MIL-101(Green), MIL-101(black), PTA@MIL-101(red) and PTA(blue)
(c) 31P solid-state MAS spectrum of PTA@MIL-101
Fig. 4 Catalyst recycling test for PTA@MIL-101
Table 1 Effect of catalyst amount.
Table 2 Effect of temperature.
Table 3 PTA@MIL-101 catalyzed Biginelli reaction with different substrates.
Scheme1 Plausible mechanism of Biginelli condensation.
Page 12 of 18

(c )
(b )
(a )
6
8
1 0
1 2
1 4
1 6
1 8
2 0
2 T h e ta (d e g r e e )
Fig.1 PXRD pattern of (a) MIL-101, (b) PTA@MIL-101, (c) recovered PTA@MIL-101
C
Cr
W
P
F
Fig.2 EDS mapping images of different elements of PTA@MIL-101
Page 13 of 18

(a)
1200
1000
800
600
400
200
0
0.0
0.2
0.4
0.6
0.8
1.0
Relative pressure(P/Po)
(b)
1800 1600 1400 1200 1000 800
600
400
-1
Wavenumber(cm )
(c)
-24
-22
-20
-18
-16
-14
-12
-10
-8
-6
Chemical shift (ppm)
Fig. 3 (a) N2 adsorption isotherm of MIL-101(Black), PTA@MIL-101(red),
(b) FT-IR spectra of recovered PTA@MIL-101(Green), MIL-101(Black),
PTA@MIL-101(red) and PTA(blue) (c)31P solid state MAS NMR spectrum
of PTA@MIL-101
Page 14 of 18

80
60
40
20
0
Fresh
Cycle 1 Cycle 2 Cycle 3
No of cycles
Fig.4 Catalyst recycling test for PTA@MIL-101
Table1: Effect of catalyst amounta
Entry Catalyst amount Yield (%)b
(mol%)
1
2
3
4
0.2
0.4
0.6
0.9
50
65
90
82
aReaction conditions: benzaldehyde (1mmol), ethylacetoacetate (1mmol), urea (1.5 mmol),
temperature= 100oC, time 1h
bIsolated yields are based on benzaldehyde
Table2: Effect of temperaturea
Entry Temperature(0C)
Yield (%)b
1
2
3
4
5
Room temperature
75
90
130
100
No desired product
60
87
88
90
aReaction conditions: benzaldehyde (1mmol), ethylacetoacetate (1mmol), urea (1.5 mmol),
PTA@MIL-101= 0.6 mol%, temperature= 100oC, time 1h
bIsolated yields are based on benzaldehyde
Page 15 of 18

Table 3: PTA@MIL-101 catalyzed Biginelli reaction with different substratesa
O
R1
X
O
O
PTA@MIL-101
NH
+
R2O
R CHO
+
NH2
H2N
1
R2O
CH3
1000C, Solvent free
N
H
X
Entry
1
R1
C6H5
4-ClC6H5
R2
X
O
O
O
O
O
O
O
O
O
O
O
O
Time(h)
Yield (%)
90
-C2H5
-C2H5
-C2H5
-C2H5
-C2H5
-C2H5
-C2H5
-C2H5
-CH3
1
2
2
2
2
2
2
3
1
2
2
2
2
82
3
4-CH3C6H5
4-BrC6H5
4-OMeC6H5
4-OHC6H5
4-NO2C6H5
3-NO2C6H5
C6H5
80
4
83
5
85
6
76
7
81
8
78
9
82
10
11
12
4-NO2C6H5
4-CH3C6H5
4-ClC6H5
-CH3
75
-CH3
78
-CH3
80
13
14
C6H5
-C2H5
-C2H5
S
S
1
2
80
85
4-ClC6H5
15
4-CH3C6H5
-C2H5
S
2
83
aReaction conditions: Substituted benzaldehyde (1mmol), dicarbonyl compound (1mmol),
urea or thiourea (1.5 mmol), PTA@MIL-101(0.6 mol%).b Isolated yields are based on
aldehyde. All compounds have been characterized by 1H and 13C NMR (available in the ESI)
Page 16 of 18

Scheme:1 Plausible mechanism of Biginelli condensation
Page 17 of 18

Graphical abstract
Keggin type phosphotungstic acid encapsulated Chromium (III) Terephthalate Metal
Organic Framework as active catalyst for Biginelli condensation
Mrinal Saikiaa,b, Diganta Bhuyan,a Lakshi Saikiaa*
aMaterials Science Division, CSIR-North East Institute of Science and Technology
Jorhat – 785006, Assam, India
bAcademy of Scientific and Innovative Research, New Delhi, India
*Corresponding author. Tel.: +91 376 2370 081; fax. +91 376 2370 011
*E-mail address: lakshi_saikia@yahoo.com
O
H
H3C
O
O
C2H5O
H3C
NH
O
C2H5O
N
O
H
O
H2N
NH2
Page 18 of 18