Dual acidic ionic liquid immobilized on α-Fe2O3-MCM-41 magnetic mesoporous materials as the hybrid acidic nanocatalyst for the synthesis of pyrimido[4,5-d]pyrimidine derivatives

Article abstract of DOI:10.1007/s10562-014-1330-5

Magnetic α-Fe₂O₃-MCM-₄₁ mesoporous material functionalized by dual acidic ionic liquid (DAIL) was prepared through a two-step approach as a novel powerful acidic catalyst which provides high ionic media for reactions, by means of post-surface grafting of the mesochannels of α-Fe₂O₃-MCM-₄₁ materials with 3-sul-fobutyl- 1-(3-propyltrimethoxysilane)imidazolium hydrogen sulfate as DAIL. Mesoporous MCM-41 was simply packed on the surface of ferric oxide nanoparticles and DAIL was efficiently incorporated into the mesochannels of MCM-41 generating Lewis and Br?nsted acidic sites. The catalyst was characterized by FT-IR, X-ray powder diffraction, HRTEM, vibrating sample magnetometer, X-ray energy diffraction spectra, thermogravimetric and differential thermal analyses, and N₂ adsorption-desorption measurements. The synthesized hybrid acidic MCM-41 showed good catalytic performance in the one-pot synthesis of pyrimido[4,5-d]pyrimidine derivatives using 6-aminouracil, aldehyde, and urea or thiourea under solvent free conditions. Moreover, it was proved that under this condition, the use of such a hybrid material as a catalyst plays the role of rendering the reactions while neither the α-Fe₂O₃-MCM-41 nor the 3-methyl-1-(4-sulfonic acid)butylimidazolium hydrogen sulfate were able to promote this reaction.

Full text of DOI:10.1007/s10562-014-1330-5

Catal Lett (2014) 144:1772–1783
DOI 10.1007/s10562-014-1330-5
Dual Acidic Ionic Liquid Immobilized on a-Fe2O3–MCM-41
Magnetic Mesoporous Materials as the Hybrid Acidic
Nanocatalyst for the Synthesis of Pyrimido[4,5-d]pyrimidine
Derivatives
•
Shahnaz Rostamizadeh Masoomeh Nojavan
•
•
Reza Aryan Mohammad Azad
Received: 15 June 2014 / Accepted: 28 July 2014 / Published online: 13 August 2014
Ó Springer Science+Business Media New York 2014
Abstract Magnetic a-Fe2O3–MCM-41 mesoporous
material functionalized by dual acidic ionic liquid (DAIL)
was prepared through a two-step approach as a novel
powerful acidic catalyst which provides high ionic media
for reactions, by means of post-surface grafting of the
mesochannels of a-Fe2O3–MCM-41 materials with 3-sul-
fobutyl-1-(3-propyltrimethoxysilane)imidazolium hydro-
gen sulfate as DAIL. Mesoporous MCM-41 was simply
packed on the surface of ferric oxide nanoparticles and
DAIL was efficiently incorporated into the mesochannels
acid)butylimidazolium hydrogen sulfate were able to pro-
mote this reaction.
Keywords Hybrid mesoporous materials Á Dual acidic
ionic liquid Á a-Fe2O3–MCM-41 Á
Pyrimido[45-d]pyrimidine derivatives
1 Introduction
¨
of MCM-41 generating Lewis and Bronsted acidic sites.
The application of conventional homogeneous acid catal-
ysis in organic synthesis has been restricted today because
of difficulty in their waste neutralization, separations,
reactor corrosion, and reusability. One of the major
research directions in the pharmaceutical and fine chemical
industries is to convert homogeneous catalytic reactions to
heterogeneous versions through different methods.
The catalyst was characterized by FT-IR, X-ray powder
diffraction, HRTEM, vibrating sample magnetometer,
X-ray energy diffraction spectra, thermogravimetric and
differential thermal analyses, and N2 adsorption–desorption
measurements. The synthesized hybrid acidic MCM-41
showed good catalytic performance in the one-pot syn-
thesis of pyrimido[4,5-d]pyrimidine derivatives using
6-aminouracil, aldehyde, and urea or thiourea under sol-
vent free conditions. Moreover, it was proved that under
this condition, the use of such a hybrid material as a cat-
alyst plays the role of rendering the reactions while neither
the a-Fe2O3–MCM-41 nor the 3-methyl-1-(4-sulfonic
The heterogenized catalysts offer the opportunity of
easy catalyst recycling which is particularly important for
precious metal catalyst [1]. In addition, the application of
many metal oxides on different supports appears to be a
good alternative as Lewis acid catalysts [2].
From a classical viewpoint with a view of recent liter-
ature reports, a support material serves to handle and
recover the catalyst and such surfaces will often act
cooperatively to stabilize specific catalyst structures [3].
Thus, researchers currently focus their attempts to precisely
positioning bi- or multifunctional groups on solid supports
for cooperative catalytic reactions [4]. Undoubtedly, this
concept of multifunctional heterogeneous or heterogenized
catalysts can be considered as a reasonable approach
toward designing economical and environmentally benign
processes [5]. For this purpose, organic–inorganic hybrid
materials have shown their efficiency in a broad range of
heterogeneous catalytic reactions [6]. High mechanical,
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-014-1330-5) contains supplementary
material, which is available to authorized users.
S. Rostamizadeh (&) Á M. Nojavan Á M. Azad
Department of Chemistry, Faculty of Science, K. N. Toosi
University of Technology, P.O. Box: 15875-4416, Tehran, Iran
e-mail: shrostamizadeh@yahoo.com
R. Aryan
Department of Chemistry, Faculty of Science, University of
Zabol, Zabol, Iran
e-mail: rezaaryan@uoz.ac.ir
123

DAIL Immobilized on a-Fe2O3–MCM-41
1773
thermal and chemical stability provided by the inorganic
components, while the organic compartments can be
independently selected and optimized for specific catalytic
applications are the major and significant features of these
catalysts.
explored. The use of microwave irradiation [14–16], long
reaction time [17] and high temperature [18] are some of the
challenging features which are included in many of the
reported methods. This catalyst in turn showed superior cat-
alytic activity in direct synthesis of pyrimido[4,5-d]pyrimi-
dine derivatives 4 from 4(6)-aminouracil 1, aldehyde 2, and
urea or thiourea 3, at 120 °C with good to excellent yields of
the products within short reaction times (Scheme 1).
Mesoporous materials such as MCM-41 possess unique
structural features such as their large surface areas, tunable
nanometer-scale pore sizes, and well-defined surface prop-
erties. Therefore, they are ideal platforms for constructing
multifunctional materials that incorporate a variety of
functional nanostructured materials among them [7]. It has
2 Experimental
¨
been shown that Si–MCM-41 lacks Bronsted acid sites and
exhibits only weak hydrogen-bonded-type sites [8].
2.1 Catalyst Preparation
Recently, the integration of mesoporous silica with
magnetic nanoparticles (NPs) to form porous magnetic
nanocomposites has undoubtedly been of great interest for
practical applications. This type of magnetic nanocom-
posites, have the advantages of both mesoporous silica and
magnetic NPs [9]. Moreover, recently the synthesis and
application of these magnetic nanocomposites has been
reported as Lewis acid catalyst in organic synthesis [10].
It must be mentioned that SO3H-functionalized ILs with
a hydrogen sulfate counter anion have been intensively
studied as a class of dual acidic functionalized ILs and there
is a considerable number of reports in the literature for the
application of these acidic ionic liquids as catalysts in
organic synthesis [11]. It is due to the fact that the existence
of both SO3H functional groups and hydrogen sulfate
counter anions can obviously enhance their acidities [12].
In the present study, the MCM-41 mesoporous material
was functionalized with ferric oxide and 3-sulfobutyl-1-(3-
propyltrimethoxysilane)imidazolium hydrogen sulfate as
dual acidic ionic liquid (DAIL), in order to produce active
and selective catalysts with Lewis acid sites associated
2.1.1 Preparation of (a-Fe2O3)–MCM-41
A mixture with molar ratio of 3.2 FeCl3:1.6 FeCl2:1
cetyltrimethylammonium bromide (CTAB):39 NH4-
OH:2300 H2O was used for the preparation of naked Fe3O4
NPs at room temperature. Typically, 2 g of iron (III)
chloride (FeCl3 Á 6H2O) and 0.8 g of iron (II) chloride
(FeCl2 Á 4H2O) were dissolved in 10 mL of distilled water
under nitrogen atmosphere. The resulting solution was
added drop wise to a 100 mL solution of 1.0 M NH4OH
solution containing 0.4 g of CTAB to construct a colloidal
suspension of magnetic iron oxide NPs.
The magnetic MCM-41 was prepared by adding 20 mL
of the magnetic colloid to a 1 L solution with the molar ratio
of 292 NH4OH:1 CTAB:2,773 H2O under vigorous mixing
and sonication. Then, sodium silicate (16 mL) was added,
and the mixture was allowed to stir at room temperature for
24 h under well-mixed conditions. The magnetic MCM-41
[(Fe3O4)–MCM-41] was collected by external magnetic
field and washed with alcoholic ammonium nitrate. The
surfactant template was then removed from the synthesized
material by calcination at 450 °C for 4 h to give the (a-
Fe2O3)–MCM-41. It is worth mentioning that in the absence
of nitrogen the magnetic property of Fe3O4 is decreased.
¨
¨
with the Bronsted acidic ILs, which have Bronsted acidity
that adds up to the introduced Lewis acid sites of the ferric
oxide species.
To investigate the characteristics and catalytic perfor-
mance of the DAIL along with mesoporous magnetic MCM-
41 system, a-Fe2O3–MCM-41–DAIL was applied in the
synthesis of valuable heterocyclic compounds such as py-
rimido[4,5-d]pyrimidine derivatives. Pyrimido[4,5-d]pyrim-
idine derivatives emerged as an important class of
heterocycles with a wide range of pharmacological and bio-
logical activities [13] and their synthesis have widely been
2.1.2 Preparation of 3-Sulfobutyl-1-(3-
Propyltrimethoxysilane)Imidazolium Hydrogen
Sulfate (DAIL)
Well ground imidazole (1.7 g, 26.5 mmol) and 3-chlor-
opropyltrimethoxysilane (4.8 mL, 26.5 mmol) were mixed
Scheme 1 (a-Fe2O3)–MCM-
41–DAIL as a magnetic
nanocatalyst for the synthesis of
pyrimido[4,5-d]pyrimidine
derivatives 4
O
R
O
X
α
(
)-MCM-41-DAIL
-Fe2O3
HN
NH
HN
H2N
X=
+
+
RCHO
Solvent
120°C
NH2
O
Free,
N
H
N
H
X
O
N
NH2
O
H
S,
4
3
1
2
123

1774
S. Rostamizadeh et al.
and refluxed in dry toluene (30 mL) under inert N2 atmo-
sphere overnight. Then, the resulting mixture was evapo-
rated in vacuo. The product N-(3-propyltrimethoxysilyl)
imidazole was obtained as a transparent liquid. To a
solution of 2.72 g (10 mmol) of the product N-(3-propyl-
trimethoxysilyl)imidazole in toluene (30 mL), 1, 4-butane
sultone (1.42 g, 10.5 mmol) was added gradually over a
period of 30 min, and then this mixture was stirred at room
temperature for 8 h. The resulting white powder was fil-
tered off and poured into flask containing concentrated
H2SO4 (0.54 mL, 10 mmol). This mixture was kept stirring
for another 8 h at 80 °C. The resulting viscous yellow
liquid was washed with diethyl ether, dried in vacuo and
characterized by IR, NMR spectra, and elemental analysis
[19–21].
catalyst and X-ray energy diffraction (XED) spectra were
recorded by scanning electron microscope model
VEGA\\TESCAN-XMU instrument with an accelerating
voltage of 20 kV. Thermogravimetric and differential
thermal analyses (TG-DTG) were carried out using a
thermal gravimetric analysis instrument (NETZSCH TG
209F1 Iris) with a heating rate of 10 °C min-1
.
2.3 Catalytic Tests
2.3.1 General Experimental Procedure for the Synthesis
of Pyrimido[4,5-d]Pyrimidine Derivatives
in the Presence of (a-Fe2O3)–MCM-41–DAIL
A mixture of 4(6)-aminouracil (1 mmol), aldehyde deriv-
atives (1 mmol), urea or thiourea (1.2 mmol), and the
catalyst (0.06 g) was ground thoroughly and then trans-
ferred into a reaction vessel where this mixture was stirred
at 120 °C for the appropriate times. The reactions were
monitored by TLC (EtOAc:Methanol, 10:2). After com-
pletion of the reaction, the mixture was allowed to be
cooled down to room temperature, DMF (3 mL) was added
and the mixture was stirred for an extra 30 min. After
collecting the magnetic catalyst with an external magnet,
H2O (10 mL) was added to the DMF solution and the
precipitates were vacuum filtered with a Buchi funnel,
dried, and recrystallized from ethanol to furnish the desired
pyrimido[4,5-d]pyrimidine derivatives.
2.1.3 Preparation of (a-Fe2O3)–MCM-41–DAIL
A mixture of (a-Fe2O3)–MCM-41 (2 g) and 3-sulfobutyl-
1-(3-propyltrimethoxysilyl)imidazolium hydrogen sulfate
(1 g) in 10 mL absolute ethanol was refluxed for 62 h.
Then the solvent was separated by vacuum filtration and
the residues were washed with diethyl ether to give (a-
Fe2O3)–MCM-41–DAIL as a brown powder (Scheme 2).
2.2 Catalyst Characterization
X-ray powder diffraction (XRD) was carried out on a
Philips X’Pert diffractometer with CuKa radiation. The
pore structure of the prepared catalyst was verified by the
nitrogen sorption isotherm ([5.0.0.3] Belsorp, BEL Japan,
Inc.). Transmission electron micrographs (TEM) were
recorded on a Philips EM-208 instrument on an acceler-
ating voltage of 100 kV. The magnetic measurement of
samples was carried out in a vibrating sample magnetom-
eter (VSM) (4 in., Daghigh Meghnatis Kashan Co., Ka-
shan, Iran) at room temperature. The morphology of the
2.3.2 The Pyrimido[4,5-d]Pyrimidine Derivatives
Characterization
Melting points were recorded on a Buchi B-540 apparatus.
IR spectra were recorded on an ABB Bomem Model
1
FTLA200-100 instrument. H and 13C NMR spectra were
measured on a Bruker DRX-300 spectrometer, at 300 and
75 MHz, using TMS as an internal standard. Chemical
α-Fe2O3
-
HSO4
-
HSO4
N+
(OMe)3Si
N+
4
O
O
OH
SO H
3
N
3
N
3
SO3H
Si
4
OH
OH
O
OH
OH
absolute EtOH
reflux
OH
Scheme 2 Preparation of (a-Fe2O3)–MCM-41–DAIL
123

DAIL Immobilized on a-Fe2O3–MCM-41
1775
Fig. 1 The FT-IR spectra of
a (a-Fe2O3)–MCM-41 and
b (a-Fe2O3)–MCM-41–DAIL
Fig. 2 The XRD patterns of a the fresh and reused (a-Fe2O3)–MCM-41–DAIL in the region of 2.0° (2h) to 10.0° (2h) and b, c the fresh and
reused (a-Fe2O3)–MCM-41–DAIL in the region of 20.0° (2h) to 80.0° (2h)
123

1776
S. Rostamizadeh et al.
Fig. 3 Nitrogen adsorption/
desorption isotherms of
a (a-Fe2O3)–MCM-41 and
b (a-Fe2O3)–MCM-41–DAIL
and BJH of c (a-Fe2O3)–MCM-
41, and d (a-Fe2O3)–MCM-41–
DAIL
shifts (d) were reported relative to TMS, and coupling
constants (J) were reported in Hertz (Hz). Mass spectra
were recorded on a Shimadzu QP 1100 EX mass spec-
trometer with 70-eV ionization potential.
Table 1 Surface area and pore volume of (Fe2O3)–MCM-41 and
(a-Fe2O3)–MCM-41–DAIL
Adsorbent
Surface area Pore volume Average pore
(m2 g-1
)
(cm3 g-1
)
diameter (nm)
(Fe2O3)–MCM-41
1,213
157
1.59
0.18
5.26
4.58
(Fe2O3)–MCM–DAIL
3 Results and Discussion
The prepared catalyst (a-Fe2O3)–MCM-41–DAIL was
characterized with FT-IR, XRD, SEM, TEM, VSM, XED
spectra, TG-DTG, nitrogen physisorption measurement,
and acid–base titration. The acidity of catalyst evaluated by
an indirect titration method [22] showed that the pH of the
catalyst is 1.90.
surface of the solid catalyst resulted in this shift
(Fig. 1a, b). The band about 1,100 cm-1 belongs to (Si–O)
stretching vibrations.
The peaks appearing at 1,460, 2,848, 2,923, and
2,969 cm-1 are attributed to the CH bending bonds of
aliphatic carbons. The peaks at 1,610 and 3,159 cm-1 are
related to the C=N stretching bond of imidazole ring and
the CH bonds of aliphatic carbons respectively. The peak at
1,168 cm-1 is related to stretching of S=O group (Fig. 1b).
XRD patterns of the fresh and reused (a-Fe2O3)–MCM-
41–DAIL catalysts are presented in Fig. 2. The XRD
analysis was performed from 2.0° (2h) to 80.0° (2h). XRD
In FT-IR spectra, the bands in the region of
400–650 cm-1 and between 1,460 and 1,610 cm-1 are
attributed to the stretching vibrations of the (Fe–O) bond in
a-Fe2O3. The small shift in the position of the peak
between 1,460 and 1,610 cm-1 is due to the fact that ionic
liquid has been supported on the surface of magnetic
MCM-41 and the interaction between ionic liquid and the
123

DAIL Immobilized on a-Fe2O3–MCM-41
1777
Fig. 4 a The SEM of (a-Fe2O3)–MCM-41–DAIL and b, c TEM images of fresh and reused (a-Fe2O3)–MCM-41–DAIL
Fig. 5 a Magnetization (M) as
a function of field (H) for (a-
Fe2O3)–MCM-41–DAIL. b The
catalyst in a typical reaction
mixture in the absence (i) and
the presence (ii) of a magnetic
field
pattern of the fresh and reused (a-Fe2O3)–MCM-41–DAIL
catalysts (Fig. 2a) displays all the characteristic peaks of
MCM-41 at corresponding to Miller indices values {h k l}
of {1 0 0}, {1 1 0}, and {2 0 0}, respectively at 2.0° (2h) to
10.0° (2h) (low-angle region) indicating a high degree of
pore symmetry of MCM-41. The XRD spectra patterns at
20.0° (2h) to 80.0° (2h) of the fresh and reused (a-Fe2O3)–
MCM-41–DAIL catalysts display diffraction peaks at
123

1778
S. Rostamizadeh et al.
Fig. 6 The XED spectra of a the fresh and b recovered (a-Fe2O3)–MCM-41–DAIL
Fig. 7 The TG and
DTG diagrams for the
(a-Fe2O3)–MCM-41–DAIL
catalyst
about 2h = *22.1°, *33.2°, *49.8°, *60.5°, *70.0°
corresponding to Miller indices values {h k l} of {2 2 0},
{3 1 1}, {4 0 0}, {4 2 2}, and {4 4 0} respectively (Fig. 2b,
c); these values are in good agreement with standard XRD
pattern of a-Fe2O3 [23]. The XRD spectra of the fresh and
reused (a-Fe2O3)–MCM-41–DAIL materials at 20.0° (2h)
to 80.0° (2h) (Fig. 2b, c) confirm the magnetic substance in
MCM-41 as a-Fe2O3 and the change of sample’s color
from black to brick-red after calcination of the catalyst is
due to the oxidation of embedded Fe3O4 to a-Fe2O3 NPs
[24].
The N2 adsorption isotherms of (a-Fe2O3)–MCM-41 fil-
led with DAIL showed a hysteresis loop resembling the type
IV isotherm with H1-type, which is characteristic of highly
ordered two-dimensional hexagonal mesostructure material
with uniform open cylindrical channels (Fig. 3a, b).
The specific surface area, pore volume, and average pore
diameter were obtained by the N2 adsorption isotherms
calculated by the Brunauer–Emmett–Teller (BET) method
[25] and found 1,213 m2 g-1, 1.59 cm3 g-1, and 5.26 nm
respectively before functionalization and 157 m2 g-1
0.18 cm3 g-1, and 4.58 nm respectively after loading ionic
,
123

DAIL Immobilized on a-Fe2O3–MCM-41
1779
Scheme 3 The model reaction
for the synthesis of
pyrimido[4,5-d]pyrimidines
Cl
CHO
O
H
N
HN
O
Cl
NH
S
α
( -Fe
)-MCM-41-DAIL
2O3
2b
N
H
NH2
O
HN
+
N
H
O
S
1
H2N
NH2
4j
3
Table 2 Optimization of one-pot synthesis of 5-(4-chlorophenyl)-
1,3,5,6,8-pentahydro-7-thioxo-pyrimido[4,5-d]pyrimidines-2,4-dione
4j in the presence of (a-Fe2O3)–MCM-41–DAIL as the catalyst
Table 3 Comparison of catalytic activity of different catalysts in the
model reaction
Entry Catalysta
Time
(h)b
Yield
(%)c
Entry
(a-Fe2O3)–MCM-
41–DAIL (g)
T (°C)
Time (h)
Yield of
4j (%)a
1
2
3
4
5
6
MCM-41
4
4
4
4
4
4
–
1
2
3
4
5
6
7
8
a
0.01
0.01
0.01
0.01
0.03
0.05
0.06
0.07
60
80
4
4
4
4
4
4
4
4
–
(a-Fe2O3)–MCM-41
MCM-41–DAIL
–
–
89
97
–
100
120
120
120
120
120
–
(a-Fe2O3)–MCM-41–DAIL
(a-Fe2O3)–MCM-41–SO3H
15
42
85
97
97
3-Methyl-1-(4-sulfonic
acid)butylimidazolium hydrogen
sulfated
32
a
b
c
d
0.06 g of catalyst was used in model reaction
Model reaction was performed at 120 °C
Isolated yields
Isolated yield
1 mmol was used in the model reaction
liquid into the catalyst pores. The results of N2 adsorption
experiments of (a-Fe2O3)–MCM-41 and (a-Fe2O3)–MCM-
41–DAIL are summarized in Table 1, in which the surface
area, pore volume, and average pore diameter of the
functionalized magnetic MCM-41 were found to be lower
than those of corresponding mesoporous silica due to
loading of DAIL. These data indicate that the ionic liquid
was successfully introduced inside the nanochannels of
(a-Fe2O3)–MCM-41 (Table 1).
VSM magnetization curves exhibited a ferromagnetic
character of (a-Fe2O3)–MCM-41–DAIL (Fig. 5a). The
saturation magnetization of (a-Fe2O3)–MCM-41–DAIL
catalyst is 2.22 emu g-1. Nevertheless, the magnetization
value of the (a-Fe2O3)–MCM-41–DAIL catalyst was quite
sufficient for common magnetic separation by using an
external magnet (Fig. 5b).
Seen from Fig. 4a, uniform and spherical morphology
of (a-Fe2O3)–MCM-41–DAIL were confirmed by SEM
image. An ordered hexagonal pore system represented in
TEM micrographs of fresh and reused (a-Fe2O3)–MCM-
41–DAIL catalyst (Fig. 4b, c).
The XED spectra of the fresh and recovered catalysts
were recorded in which no sign of degradation of the
loaded ionic liquid as well as leaching of embedded NPs
was observed according to relative peak surfaces (Fig. 6).
In addition, TG-DTG were conducted to determine the
amount of organic composition and to assess the thermal
stability of modified (a-Fe2O3)–MCM-41–DAIL material
The magnetic properties of the (a-Fe2O3)–MCM-41–
DAIL catalyst were evaluated at room temperature and the
Scheme 4 Synthesis of
pyrimido[4,5-d]pyrimidine
derivatives under optimized
reaction conditions
RCHO
O
R
α
( -Fe2O3)-MCM-41-DAIL
H
N
O
(0.06gr)
X
HN
NH
+
HN
H2N
NH2
O
N
NH2
N
X
T= 120° C
Solvent free
H
H
O
X= O, S
123

1780
S. Rostamizadeh et al.
Table 4 Synthesis of
Entry
Product
Time (h)
Yielda (%) M.P (°C)Found
pyrimido[4,5-d]pyrimidine
derivatives in solvent free
conditions catalyzed with
(a-Fe2O3)–MCM-41–DAIL
O
HN
NH
1
4a
4b
3
95
97
244
298
O
N
N
H
O
H
O
O
O
HN
NH
NH
O
2
3
8
8
Cl
O
N
H
HN
O
NH
4c
98
400
NH
O
NC
N
H
HN
O
NH
NH
O
4
5
4d
4e
4
3
93
92
316
243
N
H
O
Cl HN
O
NH
NH
O
Cl
N
H
O
HN
O
NH
NH
6
7
4f
3
8
97
91
255
221
N
O
H
O
OH
NH
HN
O
4g
N
H
N
O
H
O
HN
O
NH
NH
8
9
4h
8
2
91
98
262
291
O
N
H
O
O
4i
HN
NH
O
N
H
N
S
H
123

DAIL Immobilized on a-Fe2O3–MCM-41
Table 4 continued
1781
Entry
Product
Time (h)
Yielda (%) M.P (°C)Found
O
HN
NH
NH
10
4j
3
97
96
277
255
Cl
O
N
S
H
O
HN
NH
NH
11
12
4k
5
5
NC
O
N
S
H
O
HN
NH
NH
4l
90
278
O
N
H
S
O
Cl HN
NH
NH
13
14
4m
4n
3
3
95
95
285
257
Cl
O
N
S
H
O
HN
NH
NH
O
N
S
H
O
OH
NH
HN
15
16
4o
4p
5
5
94
91
199
235
O
N
N
S
H
H
O
HN
NH
NH
O
O
N
S
H
a
Isolated yield
with heating from room temperature to 850 °C under
argon flow. Seen from Fig. 7, an initial weight loss of
4.44 % can be assigned to the release of adsorbed mois-
ture, and then the material decomposed within two steps:
the weight loss of 1.99 % at 150 °C and a weight loss of
35.56 % at about 200 °C. The two weight losses of 35.56
and 1.99 % (totally 37.55 %) are due to the decomposi-
tion of ionic liquid organic substance. Thus the prepared
catalysts were stable against thermolysis and are suitable
for the use in the reaction under consideration below
150 °C.
Then, the reaction of 6-aminouracil 1 (1 mmol),
4-chlorobenzaldehyde 2b (1 mmol), and thiourea
3
(1.2 mmol), was chosen as the model reaction with various
amounts of (a-Fe2O3)–MCM-41–DAIL as the catalyst at
different temperatures under solvent-free conditions
(Scheme 3, Table 2).
As indicated in Table 2, the best yield for 4j was
obtained when 0.06 g of the catalyst was used at 120 °C
(Table 2, Entry 7). Further increasing the amount of cata-
lyst neither did affect the yield nor the reaction time
(Table 2, Entry 8).
123

1782
S. Rostamizadeh et al.
In order to compare the efficiency of this hybrid organic–
inorganic catalyst with its building components, a-Fe2O3–
MCM-41 (not charged with DAIL), a-Fe2O3–MCM-41–
SO3H, MCM-41, DAIL–MCM-41, and 3-methyl-1-(4-sul-
fonic acid)butylimidazolium hydrogen sulfate were sepa-
rately examined under the optimized condition (Table 3).
Significant distinction in the catalytic activities was
clearly ascertained by taking into account the results of
Table 3. When MCM-41, a-Fe2O3–MCM-41, and a-
Fe2O3–MCM-41–SO3H were used as catalyst in the
model reaction, no product was obtained (Table 3, Entries
1, 2, and 5) which indicates that acidic character or high
surface area alone is not sufficient for the reaction. Com-
parison of magnetic MCM-41–DAIL with non-magnetic
MCM-41–DAIL (Table 3, Entries 3 and 4), showed that
the presence of ferric oxide in the solid catalyst as Lewis
acid, resulted in higher yields for the reaction. Notably, the
use of ionic liquid 3-methyl-1-(4-sulfonic acid)butylimi-
dazolium hydrogen sulfate was shown to give consider-
ably low product yield (32 %) (Table 3, Entry 6),
demonstrating the significance of supporting DAIL on
hybrid organic–inorganic material to reach high catalytic
activity (Table 3, Entry 4). The introduction of DAIL to a-
Fe2O3–MCM-41 leads to the formation of a highly polar
reactive medium inside the pores of the magnetic MCM-41
material. On the other hand, the high polar nature of DAIL
Scheme 5 Catalytic reusability of (a-Fe2O3)–MCM-41–DAIL
As shown in Table 4, this reaction was fairly general,
clean, rapid, and efficient under the optimized reaction
conditions in the presence of (a-Fe2O3)–MCM-41–DAIL.
4 Conclusion
In summary, we have introduced a multifunctional solid
acid catalyst that shows remarkable and somehow
extraordinary catalytic activity in the synthesis of pyrimi-
do[4,5-d]pyrimidine derivatives at ambient temperature
under solvent-free conditions. It is believed that the
À
having two acidic SO3H and HSO4 acidic sites and high
surface area of the magnetic mesoporous material pos-
sessing Lewis acidic species (Fe3?) cooperated synergis-
tically with each other. This means that a very well-
distributed highly polar and acidic medium develops
inside the pores of magnetic MCM-41 with the advantage
of a high probability for the starting materials to react and
causes the reaction to be proceeded most efficiently lead-
ing to best yield (Table 3, Entry 4). These observations
clearly highlight the cooperation between acidic and ionic
strength of various components incorporated in the cata-
lyst structure in promoting the reaction toward synthesis of
pyrimido[4,5-d]pyrimidines.
¨
Bronsted acidity and high ionic strength of DAIL together
with Lewis acidity of ferric oxide might increase the cat-
alytic activity inside the pores of the magnetic nanocata-
lyst. Good to excellent yields of the products, remarkably
short reaction times, high reactivity for aldehydes with
various electron demands and outstanding reusability of the
catalyst are the most important features of the present
work.
Acknowledgments The authors gratefully acknowledge K. N. To-
osi University Research Council for partial financial support of this
study.
In order to examine the scope and generality of the pro-
cess, we then explored the synthesis of various pyrimido
[4,5-d]pyrimidine derivatives under optimized reaction
conditions. The results are summarized in Table 4. These
results indicate the fact that the use of as low as 0.06 g of (a-
Fe2O3)–MCM-41–DAIL exhibits marked efficiency for all
of the reactants tested under the optimized reaction condi-
tions (Scheme 4, Table 4).
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