Accepted Manuscript

Title: Silica Nanoparticles Immobilized Benzoylthiourea

Ferrous Complex as an Efficient and Reusable Catalyst for
One-pot Synthesis of Benzopyranopyrimidines

Author: Farnaz Movahedi Sara Amirnejat Hassan Masrouri

Meysam Mohadesi M.Z. Kassaee

PII: S1381-1169(13)00229-X
DOI: http://dx.doi.org/doi:10.1016/j.molcata.2013.05.023
Reference: MOLCAA 8776

To appear in: Journal of Molecular Catalysis A: Chemical

Received date: 26-12-2012

Revised date: 25-5-2013
Accepted date: 31-5-2013

Please cite this article as: F. Movahedi, S. Amirnejat, H. Masrouri, M.

Mohadesi, M.Z. Kassaee, Silica Nanoparticles Immobilized Benzoylthiourea Ferrous
Complex as an Efficient and Reusable Catalyst for One-pot Synthesis of
Benzopyranopyrimidines, Journal of Molecular Catalysis A: Chemical (2013),
http://dx.doi.org/10.1016/j.molcata.2013.05.023

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Silica Nanoparticles Immobilized Benzoylthiourea Ferrous Complex

as an Efficient and Reusable Catalyst for One-pot Synthesis of

Benzopyranopyrimidines

t
Farnaz Movahedia, Sara Amirnejatb, Hassan Masrouria, Meysam Mohadesib and

ip
M.Z. Kassaee*,b

cr
a
Department of Chemistry and Petrochemical Engineering, Standard Research

Institute, P.O. Box 31745-139, Karaj, Iran

us
b
Department of Chemistry, Tarbiat Modares University, P.O. Box 14155-4838,

Tehran, Iran

Abstract: an
M
Benzoylthiourea Fe(ΙΙ) Complex was supported on silica nanoparticles and employed

as a heterogeneous catalyst in preparation of benzopyranopyrimidines through one-

d

pot condensation reaction of salicylaldehydes, malononitrile and secondary amines in

te

EtOH, at room temperature. The prepared catalyst was characterized by BET, ICP,
p

FT-IR, TGA, SEM-EDX, TEM and Elemental analysis. The catalyst could be
ce

recovered easily and reused at least five times without significant loss of its catalytic

activity.
Ac

Keywords: Benzopyranopyrimidines, Nanohybrid catalyst, Silica nanoparticles, Fe(ΙΙ)

complex, Heterogeneous catalysis

1. Introduction

*
Corresponding author. Tel.: +98-912-1000392; Fax: +98-21-88006544
E-mail: kassaeem@modares.ac.ir (M.Z. Kassaee).

Page 1 of 24
Chemical industries are investing in specific strategies to catalyze organic reactions

environmentally benign and commercially profitable [1, 2]. Although homogeneous

catalysis has demonstrated high activity and selectivity at milder conditions for a wide

variety of reactions, their use has been limited for difficulties of at the stage of

t
separation catalytic resource from products [3]. In this respect, various heterogeneous

ip
catalysts have been synthesized and tested in the last decades, which were based

cr
either on metal oxides or supported precious metals [4–8]. Despite stability, durability

and good catalytic activity, these catalysts suffer from leaching of their active

us
ingredients. Therefore, chemists are inspecting systems with less expensive but stable

an
and catalytically active compounds [7]. Indeed, anchoring of homogeneous catalysts

onto solid supports, prepare their heterogenic analogs with desirable high catalytic
M
activity, possibility of recovery, and reuse characteristics. The other significance of

this point is inhibition of catalyst leaching, especially when the homogeneous

d

catalysts are anchored covalently onto the suitable supports [9, 10].
te

On the other hand, the preferences which should be considered to choose a solid

support including vast surface area, tunable pore sizes, high thermal, mechanical
p

stability via the feasibility in surface functionalization, specify silica nanoparticles as

ce

an alternative for immobilization of catalytic resources. The high external surface area

of these nanoparticles reduces the mass transfer limitations in liquid-phase reactions.

Ac

In addition, their surface can be modified with diverse functionalities which allow for

a wide range of strategies to covalently attach the main catalytic active species, in

order to prevent metal leaching and thus to increase catalyst stability and its possible

reuse in the process [11-16].

Designing diverse procedures to produce biologically active compounds has been led

to an important area of research in organic, combinatorial, and medicinal chemistry

Page 2 of 24
named multicomponent reactions (MCRs) [17-20]. The MCR strategy represents

flexibility and atom efficiency in which lays it superior to conventional linear-type

synthesis [21, 22]. Producing combinatorial small heterocyclic molecules as a value in

the research track for novel desired structures is influenced by the advances

t
discovered in heterocyclic MCR methodologies [23, 24]. In this respect

ip
environmentally benign multicomponent procedures are inclined toward those

cr
methods in which loss of catalytic supplies is prevented with possible recycling.

Finally, benzopyranopyrimidines have provided an important pharmacophore

us
synthesized research platform for chemists. This is because of there specific

an
characteristics which consist of anti-inflammatory, analgesic, in vivo antitumor, in

vitro anti-aggregating activities as well as cytotoxic activity against cancer cell lines,
M
and causing significant perturbation in cell cycle kinetics [25-30]. In this respect, lots

of methods have been developed for the preparation of benzopyranopyrimidine

d

derivatives [25-35] while none of them contain recyclable and reusable catalysts in
te

their protocols.

Iron complexes have attracted lots of consideration as catalysts in organic chemistry

p

due to a number of advantages involving low price, non-toxicity and environmentally

ce

benign character [36-43]. Utilization of Iron-based catalyst systems has been reported

for carbon–heteroatom [44, 45] and carbon–carbon bond-forming reactions [40, 46-
Ac

47], cross-coupling [39], isomerization, and cycloaddition [46, 48–50], oxidations

[51, 52] and reductions [53]. Their application is comparable with other transition

metal catalytic systems in natural product syntheses from the point of yield and

selectivity [54, 55].

In the present work, immobilization of a benzoylthiourea Fe(ІІ) complex on silica

nanoparticles (SNPs) led to a new heterogeneous system in which its catalytic activity

Page 3 of 24
was investigated for one-pot synthesis of benzopyranopyrimidines through pseudo

four-component condensation reaction of salicylaldehydes, malononitrile and

secondary amines in EtOH at room temperature.

t
2. Experimental

ip
2.1. Chemicals and instruments

cr
The reagents and solvents used in this work were obtained from Fluka or Merck and

used without further purification. Aerosil 200 silica powder was purchased from

us
Degussa, with a quoted surface area of 200 m2g−1 and a primary particle diameter of

an
20 nm. Fourier transform infrared spectroscopy (FT-IR) measurements were

performed using KBr disc on a Thermo IR-100 infrared spectrometer (Nicolet).

M
Elemental analyses for C, H and N were performed using a Heraeus CHN–O–Rapid

analyzer. The thermogravimetric analysis (TGA) curve was recorded using a

d

TGA/DTA 6300 (manufactured by SΙΙ Nanotechnology Inc.). The particle size and
te

morphology were investigated by a transmission electron microscope (TEM,

EM208S, Netherlands, on an accelerating voltage of 100 kV), and scanning electron

p

microscope (SEM, Holland Philips XL30 microscope with an accelerating voltage of

ce

25 kV). The Brunauer-Emmett-Teller (BET) surface area of the catalyst was studied

using a nitrogen adsorption instrument (Micrometrics ASAP 2020). A radial view

Ac

Varian Vista-Pro simultaneous ICP-OES (Springvale, Australia) coupled to a V-

groove nebulizer and equipped with a charge coupled device (CCD) was applied for

determination of the Fe(ΙΙ) ions. The 1H- and 13C-spectra were measured at 500.1, and

125.7 MHz, respectively,on a Bruker DRX 500-Avance FT-NMR instrument with

CDCl3 solvent.

Page 4 of 24
2.2. Preparation of SNPs functionalized with (3-aminopropyl)-triethoxysilane

(APTES-SNPs)

Silica nanoparticles (5 g) were dispersed in a solution of deionized (DI) water and

concentrated hydrochloric acid (300 mL, volume ratio, 1:1), activated by refluxing for

t
24 h, then washed at least three times with DI water and dried for 12 h. Organic

ip
modification of SNPs with (3-aminopropyl)-triethoxysilane (APTES) was performed

cr
by stirring 5 g of SNPs with 1 ml of APTES in dry toluene and refluxing for 24 h

under nitrogen atmosphere. The resulting white solid product (APTES-SNPs) was

us
centrifuged and washed with absolute ethanol and DI water, then dried for 12 h under

an
vacuum making it ready for the next modification stage [56].
M
2.3. Synthesis of Benzoylthiourea functionalized SNPs (BTU-SNPs)

To a solution of 10 mmol benzoyl chloride in dry acetone was added 10 mmol KSCN
d

and refluxed 30 min to yield benzoyl isothiocyanate [57]. Then, APTES-SNPs (2 g)

te

were added to react with benzoyl isothiocyanate in the reflux conditions in dry

toluene for 5 h. The resulting pale yellow solid was centrifuged and was washed
p

thoroughly with DI water, acetone and absolute ethanol, then dried at 100 ºC for 24 h
ce

to provide the corresponding benzoylthiourea functionalized SNPs (BTU-SNPs) [58].

Ac

2.4. Immobilization of FeCl2 on Benzoylthiourea functionalized SNPs (Fe(ІІ)-BTU-

SNPs)

In order to anchoring Fe(ΙΙ) onto the surface of BTU-SNPs, anhydrous FeCl2 (1.5

mmol, 190 mg) was added in one portion to a solution of BTU-SNPs (2 g) in dry

acetone (50 ml), and stirred for 4 h at room temperature. The as prepared solid

complex was separated by centrifugation (RCF = 6000×g, 10 min), then washed with

Page 5 of 24
DI water, acetone and absolute ethanol to remove the unattached substrates, and

subsequently dried at 100 ºC for 16 h to furnish the desired Fe(ІІ)-BTU-SNPs

heterogeneous complex.

2.5. General procedure for the synthesis of benzopyranopyrimidines (3a-o)

t
To a 10mL round-bottomed flask were added salicylaldehyde (2 mmol), malononitrile

ip
(1 mmol), secondary amine (1 mmol), EtOH (3 ml), and Fe(ІІ)-BTU-SNPs (15 mg).

cr
The suspension was stirred vigorously for the required reaction time, at room

temperature (see Table 1). The progress of the reactions was monitored by TLC

us
(eluent: EtOAc/n-hexane, 1:3). After completion of the reaction, the catalyst was

an
removed from the mixture via sintering in hot EtOH, and then reused as such for the

next experiment after washing with EtOH and CH2Cl2. Upon cooling of the remained
M
alcoholic aqueous phase, the crude product was precipitated, then was filtered and

washed with H2O and EtOH to afford the pure benzopyranopyrimidine derivative (3a-
d

o).
te

3. Results and discussion

p

3.1. Synthesis and characterization of Fe(ІІ)-BTU-SNPs

ce

Scheme 1 represents the synthetic strategy for covalently immobilization of Fe(ІІ)

onto the silica nanoparticles (Fe(ІІ)-BTU-SNPs); SNPs were coated with 3-

Ac

aminopropyltriethoxysilane (APTES) to achieve amino-functionalized silica

nanoparticles (APTES-SNPs) in which subsequently reaction with benzoyl

isothiocyanate led to the immobilization of the benzoylthiourea functionality on the

SNPs through a propyl tether (BTU-SNPs). Ultimately, anchoring ferrous chloride

with benzoylthiourea ligand led to preparation of the desired catalytic resource

(Fe(ІІ)-BTU-SNPs). The coordination chemistry of aroylthioureas to a number of

Page 6 of 24
transition metals has been reported previously [59, 60]. These studies clearly have

demonstrated existence of two coordination mode of [M(L-O,S)2] and [M(L-S)2X2]

for two valence transition metals (M2+). For Benzoylthiourea ligands with

intramolecular hydrogen bond between the thiourea -C(S)NHR moiety and the

t
oxygen atom of the amidic moiety, generally coordination occurs through the S donor

ip
atom to the metal ions in mono-dentate fashion. Elemental analysis showed loading of

cr
0.93 mmol/g benzoylthiourea moiety onto the SNPs, corresponding to S content of

2.98 %. The metal loading in catalyst was determined by Inductively Coupled Plasma

us
(ICP) and found to be 0.46 mmol/g of iron which is in good agreement with the

an
results obtained from TGA and admits the ratio of 1:2 of ferrous (II) chloride to the

grafting ligand.
M
d
p te
ce
Ac

Page 7 of 24
 O
O
Si
Si O
OH O
Si
OH O
HO O
Si
OH O O
HO

(EtO) 3Si NH2

HO OH O S
O

HO OH
Toluene, N 2, R ef lux, 24 h O
Si O
Si

t
O
HO OH
O

ip
O O
HO OH O Si

SiO 2 NPs (SNPs) Si O

cr
Benzoyl iso

us
Toluene, R

an
O
O
Si
Si O
O
Si O
O Si
O
O
M
O S

O Ph O

H Si
O O
S
d
O
O
O
N NH O
O
Si O
O Si
Si O
te

Si O
O Si O
O
Si S
O O
O

Cl Fe FeCl 2, dry acetone

p

O Si Cl
O
O
r.t., 4 h
O
ce

Si O S
O
O Si
O
O Si
O
NH O
N O
Si
Si O Si O
Ac

O
Si O
H Ph O Si
O O
Fe(II)-BTU-SNPs O

O S

O O
Si S
O
O
O O
O Si

Si O

Scheme 1

Page 8 of 24
Successful surface modification of the SNPs with Fe(ΙΙ)-BTU was evidenced by

Fourier transform infrared (FT-IR) spectral analysis. One strong absorption band at

1087 cm-1 was attributed to the stretching vibrations of the silica (Si–O–Si) network

and an O–H stretching vibration due to physisorbed water and potentially surface

t
hydroxyls near 3432 cm−1 (Fig. 1a). The significant features observed for the APTES

ip
functionalized SNPs were the appearance of the peaks at 2914 and 3457 cm-1

cr
attributed to C-H and N-H stretching vibrations of propylamine moiety, respectively

(Fig. 1b) [61, 62]. Observation of a band at 1659 cm-1 which is assigned to the C=O

us
stretching vibration as well as 1537 cm-1 due to the asymmetric stretching vibrations

an
of N-C-N, verifies successfully modification of amine groups to benzoylthiourea. The

peaks due to C–N stretching vibration, Si–CH2–R and C=S stretching frequencies are

usually observed in the range of 1000–1200, 1200–1250 and 1282–1355 cm-1

M
respectively, did not observed in all spectra because they were masked by Si–O–Si
d

stretching band [63, 64]. The peaks attributed to N1-H1 stretching vibration and intra-
te

molecular hydrogen bonds of N2-H2 with carbonyl moiety were evidenced at 3440

and 3261 cm-1, respectively. Also, the band at 2353 cm-1 in the spectrum should be
p

assigned to the stretching vibration of S-H which indicates existence of an S-H group
ce

in the free ligand as a result of thione–thiol tautomerism (Fig. 1c) [65]. The absorption

band attributed to the stretching vibration of S-H group disappeared as the ligand
Ac

coordinated to Fe(II), while the stretching frequencies of the C=O and N-H remained

in the same region in the corresponding complex, indicating the strong possibility of

coordination occurring only through the S atom (Fig. 1d) [64].

Page 9 of 24
 t
ip
cr
us
251658240

an
Fig. 1: The comparative FT-IR spectra for (a) SNPs (b) APTES-SNPs (c) BTU-SNPs

and (d) Fe(ІІ)-BTU-SNPs.

M
The thermogravimetric analysis (TGA) curves of the BTU-SNPs and Fe(II)-BTU-
d

SNPs showed mass loss of the organic materials as they decomposed upon heating
te

(Fig. 2). They were studied by thermogravimetric analysis from the ambient

temperature to 873 K in nitrogen atmosphere. BTU-SNPs displayed decomposition in

p

two steps; a gradual mass loss of about 1.6% on heating from 25 to 137 °C was
ce

attributed mainly to the loss of water [66] while a major loss of mass about 15.8%

was observed at 332-580 ºC and attributed to decomposition of the anchored organics.

Ac

The initial mass loss due to decomposition of organics was achieved at 332 °C, higher

than that of the boiling point of liquid (3-aminopropyl)-triethoxysilane confirming

that the relatively thermally stable aminopropyl groups were chemically bonded on

the surface of the SNPs [67]. The total mass losses attributed the grafting ligand was

showed to be 20.7% (Fig. 2a). A gradual mass loss of about 3.2% was achieved up to

117 ºC due to the loss of the adsorbed water on the surface of the catalyst. A major

Page 10 of 24
drop of 23.4% was observed at 230-560 ºC and the total mass loss was gained 26.6%

owing to the anchored complex (Fig. 2b). Regarding to the variance of the calculated

amounts of the mass drop in TGA curves, it was found that value of the anchored

ferrous chloride is 0.47 mmol/g of catalyst which is in good agreement with the

t
obtained results from ICP (0.46 mmol/g).

ip
cr
us
an
M
d

251658240
te

Fig. 2: TGA curves of (a) BTU-SNPs and (b) Fe(II)-BTU-SNPs.

p

The energy dispersive X-ray spectroscopy EDX (Fig. 3a) analysis shows the Si and
ce

Fe elements, which confirm the elemental composition of the sample. The SEM and

TEM micrographs provide more accurate information on the particle size and
Ac

morphology of the functionalized SNPs (Fig. 3b, 3c). The SEM images of the all

samples show that the nanoparticles have a uniform size, spherical shape, and

disordered mesopores. The shape of the carrier is retained even after immobilization

with the organic groups and the complex formation. The nature of the complex does

not have significant impact on the morphology of the SNPs. TEM images indicate that

the nanoparticles developed in this work are highly monodispersed with the average

Page 11 of 24
diameter estimated around 34 nm. The BET surface area for Fe(ІІ)-BTU-SNPs was

found to be 103 m2g-1. This was as anticipated, since the surface area of the Fe(ІІ)

complex functionalized SNPs was decreased considerably compared to the bare ones,

indicating presence of the anchored organic ligands in the pore channels of SNPs [68].

t
Indeed, occupying pore sites because of anchoring the corresponding complex has led

ip
to the lower N2 uptake.

cr
251658240

us
an
M
d
te

Fig. 3: (a) The EDX analysis of catalyst, (b) SEM and (c) TEM images of the Fe(ІІ)-
p

BTU-SNPs.
ce
Ac

3.2. Evaluation the catalytic activity of Fe(ІІ)-BTU-SNPs through synthesis of the

benzopyranopyrimidines

We investigated the catalytic activity of Fe(ІІ)-BTU-SNPs as a heterogeneous catalyst

in one-pot synthesis of benzopyranopyrimidines through pseudo four-component

reaction of salicylaldehydes, malononitrile and secondary amines (Scheme 2) and the

results are summarized in Table 1. For this purpose, the reaction of salicylaldehyde,

Page 12 of 24
malononitrile and morpholine as a simple model reaction was probed in order to

establish the feasibility of the strategy and optimize the reaction conditions. The

reaction did not proceed in the absence of the catalyst or even in the presence of

SNPs. However, high product yields were obtained using either iron(ΙΙ) chloride or

t
Fe(ΙΙ) anchored SNPs (Table 1, entries 3 and 8, respectively). All the same, lack of

ip
recyclability of the former limited its application for further use. To overcome this

cr
problem and uncertainty, FeCl2 is anchored on SNPs through a covalently

incorporation of an organic entity. In these types of the solid catalysts the reactive

us
center is highly mobile similar to homogeneous catalysts and at the same time the

an
advantage of recyclability is accessible.

NR 2
M
NC CN

Fe(II)-BTU-SNPs
R 2NH
d

2 EtOH, r.t.
te

CHO O N
X
3a-o
p
ce

OH
X
1
Ac

Scheme 2

To appraise the effects of media, the reaction was carried out in various organic

solvents by using Fe (ІІ)-BTU-SNPs (15 mg per 1 mmol of reactants) as the catalyst,

where the best results appeared in EtOH, at room temperature. To investigate the

effect of the catalyst concentration, systematic studies were carried out in the presence

of different amounts of the catalyst (10, 15, 30 mg) in EtOH, affording

Page 13 of 24
benzopyranopyrimidines with 78%, 95% and 95% isolated yields, respectively. Thus,

the best yield is accessible in the presence of just 15 mg Fe(ІІ)-BTU-SNPs, and use of

higher amounts of the catalyst (30 mg) did not improve the result to an appreciable

extent.

t
ip
Table 1: Optimization of Fe(ІІ)-BTU-SNPs catalyzed model reaction for synthesis of

cr
benzopyranopyrimidines.a

Entry Catalyst Solvent Time Yield (%)b

us
1 No catalyst EtOH 10h Nil

an
2 Silica nanoparticles (20 mol%) EtOH 10h Nil

3 FeCl2 (15 mol %) EtOH 4h 94

M
4 Fe(ІІ)-BTU-SNPs (15 mg) CH3CN 8h 34

5 Fe(ІІ)-BTU-SNPs (15 mg) Toluene 10h 26

d

6 Fe(ІІ)-BTU-SNPs (15 mg) H2O 8h 15

te

7 Fe(ІІ)-BTU-SNPs (10 mg) EtOH 4h 78

8 Fe(ІІ)-BTU-SNPs (15 mg) EtOH 4h 95

p
ce

9 Fe(ІІ)-BTU-SNPs (30 mg) EtOH 10h 95

a
Reaction conditions: salicylaldehyde (2 mmol), malononitrile (1 mmol), morpholine (I mmol),

catalyst, solvent (3 ml), room temperature.

Ac

b
Isolated yields.

The reaction can tolerate α-hydroxybenzaldehydes and some of its derivatives

carrying either electron-donating or halogen substituents in the ortho, meta and para

positions and the results were reasonable (Table 2). Aliphatic amines such as diethyl

amine and dibutyl amine did not react while the best results were achieved with cyclic

Page 14 of 24
secondary amines. All products were characterized on the basis of their elemental

analysis and spectroscopic data such as FT-IR, 1H and 13C NMR spectra.

Table 2: One-pot synthesis of benzopyranopyrimidines by the reaction of salicylaldehydes,

t
malononitrile and secondary amines in the presence of Fe(ІІ)-BTU-SNPs in EtOH.a

ip
Entry Amine Aldehyde Product Yield (%)b

1 dimethyl amine 2-hydroxy benzaldehyde 3a 90

cr
2 diethyl amine 2-hydroxy benzaldehyde 3b nil

us
3 dibuthyl amine 2-hydroxy benzaldehyde 3c nil

4 morpholine 2-hydroxy benzaldehyde 3d 93

5 pyrrolidine 2-hydroxy benzaldehyde 3e 95

7
4-methyl piperidine

morpholine
an
2-hydroxy benzaldehyde

2-hydroxy-4-methoxy benzaldehyde
3f

3g
89

97
M
8 dimethyl amine 5-chloro-2-hydroxyl benzaldehyde 3h 88

9 morpholine 5-chloro-2-hydroxyl benzaldehyde 3i 90

d

10 4-methyl piperidine 5-chloro-2-hydroxyl benzaldehyde 3j 92

11 4-methyl piperidine 2-hydroxy-5-methoxy benzaldehyde 3k 85

te

12 pyrrolidine 5-chloro-2-hydroxyl benzaldehyde 3l 94

p

13 morpholine 3,5-dichloro-2-hydroxy benzaldehyde 3m 91

ce

14 4-methyl piperidine 3,5-dichloro-2-hydroxy benzaldehyde 3n 96

15 morpholine 5-bromo-2-hydroxyl benzaldehyde 3o 93

a
Reaction conditions: Aldehyde (2 mmol), malononitrile (1 mmol), amine (1 mmol), Fe(ІІ)-BTU-SNPs (15 mg),
Ac

EtOH (3 mL), room temperature.

b
Isolated yields.

In order to investigate the catalytic activity and the possibility of the catalyst

recyclability and reusability, the Fe(ІІ)-BTU-SNPs was recovered from the reaction

mixture by simple filtration in hot EtOH. The separated catalyst was dried in vacuum

oven at 100 °C and was reused as such for subsequent experiments under similar

Page 15 of 24
reaction conditions. The results showed that the catalyst could be effectively used for

at least five consecutive cycles without much appreciable loss in its catalytic activity

(Table 3). The recyclability data demonstrate high stability of the catalyst under the

reaction conditions. In addition, an important factor which should be studied for this

t
kind of heterogeneous system is the possibility of leaching of some active metal into

ip
the reaction mixture. Therefore the filtrates were tested for the presence of iron after

cr
each catalytic cycle by ICP. It was found that no active species were present in the

supernatant in which rules out the contribution of any homogeneous catalysis system.

us
an
Table 3: Reusability of the Fe(ІІ)-BTU-SNPs catalyst.a

Cycles Yield (%) Recovery of Fe(ІІ)-BTU-SNPs (%)

fresh 93 99
M
1 93 97

2 92 96
d

3 91 94
te

4 91 94

5 90 92
p

a
Reaction conditions: salicylaldehyde (2 mmol), malononitrile (1 mmol), morpholine (I mmol),
ce

Fe(ІІ)-BTU-SNPs (15 mg), EtOH, room temperature.

Ac

A plausible mechanism for the formation of the product would be as follows: the

catalyst facilitates the Knoevenagel condensation reaction through Lewis acid sites

(Fe2+) which are coordinated to the oxygen of the salicylic aldehyde 1 and activate it

for nucleophilic attack of Malononitrile. On the other hand, catalyst can activate O-H

groups so that the Pinner reaction (45) occurs in the presence of Lewis basic sites

such as O2- from the SiO2. Next, the cyano group of intermediate 5 can be attacked by

the amine 2 to produce intermediate 6. Finally, intermediate 6 reacts with another

Page 16 of 24
molecule of salicylic aldehyde followed by proton transfer to afford the final

benzopyranopyrimidine 3. In fact, the formation of product proceeds through

activating reactants with both Lewis acid and basic sites of catalyst (Scheme 3).

Fe2+
O

t
X

ip
X CN X CN
H
+

cr
CN N
OH OH O NH
1 4 5

us
Fe2+
NR 2 O OH NR2
H
X

an
X

NH H N
+
M
O NH O N
X
H
6 1 7
d

Scheme 3
te

4. Conclusion
p

Fe(ΙΙ)-benzoylthiourea complex has been anchored covalently into the organic-

ce

modified SNPs in order to prepare a new interphase nanocatalyst. This heterogenized

solid catalyst has been proved to be highly active towards one-pot synthesis of
Ac

benzopyranopyrimidines via pseudo four-component coupling reactions of α-

hydroxybenzaldehydes, malononitrile and secondry amines in EtOH, at room

temperature. The prepared catalyst offers several advantages including high

concentration of catalytically active sites cooperated with a silica nanoparticle-support

with high surface area as well as ease of separation, and recyclability of the catalytic

resource desired environmentally and economically.

Page 17 of 24
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[1]. Corma, Chem. Rev. 95 (1995) 559–614.

[2]. Corma, H. Garcia, Catal. Today 38 (1997) 257–308.

t
[3]. P.T. Anastas, J.C. Warner, Green Chemistry: Theory and Practice, Oxford

ip
University Press, New York, 1998, p.30.

cr
[4]. F. Luck, Catal Today 53 (1999) 81–91.

us
[5]. K. Pirkanniemi, M. Sillanpää, Chemosphere 48 (2002) 1047–1060.

an
[6]. F. Stüber, J. Font, A. Fortuny, C. Bengoa, A. Eftaxias, A. Fabregat, Top Catal

33 (2005) 3–50.
M
[7]. J. Levec, A. Pintar, Catal Today 124 (2007) 172–184.

[8]. A. Cybulski, Ind Eng Chem Res 46 (2007) 4007–4033.

d
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*Graphical Abstract (for review)

Silica Nanoparticles Immobilized Benzoylthiourea Ferrous Complex as

an Efficient and Reusable Catalyst for One-pot Synthesis of
Benzopyranopyrimidines

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Farnaz Movahedia, Sara Amirnejatb, Hassan Masrouria, Meysam Mohadesib and
M.Z. Kassaee*,b

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a
Department of Chemistry and Petrochemical Engineering, Standard Research Institute, P.O.
Box 31745-139, Karaj, Iran
b
Department of Chemistry, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran

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Benzoylthiourea Fe(ΙΙ) Complex was supported on silica nanoparticles and employed as a
an
heterogeneous catalyst in preparation of benzopyranopyrimidines through one-pot condensation
reaction of salicylaldehydes, malononitrile and secondary amines in EtOH, at room temperature.
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*Research Highlights

Research highlights

 Synthesis of nanosilica immobilized benzoylthiourea iron complex (Fe(ІІ)-BTU-SNPs)

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 High catalytic activity of Fe(ІІ)-BTU-SNPs in synthesis of benzopyranopyrimidines

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 Reusability of Fe(ІІ)-BTU-SNPs without significant loss of its catalytic activity

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