Synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3-d]pyrimidinone derivatives using Fe3O4@Ph-PMO-NaHSO4 as a new magnetically separable nanocatalyst

Article abstract of DOI:10.1166/jnn.2019.16032

Immobilized NaHSO₄ on core/shell phenylene bridged periodic mesoporous organosilica magnetic nanoparticles (Fe₃O₄@Ph-PMO-NaHSO₄) as a new acidic magnetically separable nanocatalyst was successfully prepared in three steps: (i) preparation of Fe₃O₄ nanoparticles by a precipitation method, (ii) synthesis of an organic-inorganic periodic mesoporous organosilica structure with phenyl groups on the surface of Fe₃O₄ magnetic nanoparticles (MNPs) and (iii) finally adsorption of NaHSO₄ on periodic mesoporous organosilica (PMO) network. The prepared organic-inorganic magnetic reagent was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), N₂ adsorption-desorption and energy-dispersive X-ray (EDX) techniques. Finally, it was used as a reusable and new catalyst to promote the synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3-d]pyrimidinone derivatives as important biologically active compounds. Eco-friendly protocol, high yields, short reaction times and easy and quick isolation of the products are the main advantages of this procedure.

Full text of DOI:10.1166/jnn.2019.16032

Article
Journal of
Nanoscience and Nanotechnology
Vol. 19, 3447–3458, 2019
Copyright © 2019 American Scientific Publishers
All rights reserved
Printed in the United States of America
www.aspbs.com/jnn
Synthesis of Tetrahydrobenzo[b]pyran and
Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives Using
Fe O @Ph-PMO-NaHSO as a New Magnetically
3
4
4
Separable Nanocatalyst
1
1ꢀ∗
2
Mahdieh Haghighat , Farhad Shirini , and Mostafa Golshekan
1Department of Chemistry, College of Sciences, University of Guilan, Rasht, 41335-19141, Iran
Institute of Medical Advanced Technologies, Guilan University of Medical Science, Rasht, 41346-45971, Iran
2
Immobilized NaHSO on core/shell phenylene bridged periodic mesoporous organosilica magnetic
4
nanoparticles (Fe O @Ph-PMO-NaHSO ꢀ as a new acidic magnetically separable nanocatalyst
3
4
4
was successfully prepared in three steps: (i) preparation of Fe O nanoparticles by a precipita-
3
4
tion method, (ii) synthesis of an organic–inorganic periodic mesoporous organosilica structure with
phenyl groups on the surface of Fe O magnetic nanoparticles (MNPs) and (iii) finally adsorption
3
4
of NaHSO on periodic mesoporous organosilica (PMO) network. The prepared organic–inorganic
4
magnetic reagent was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray
IP: 46.161.60.137 On: Sun, 17 Mar 2019 02:32:34
powder diffraction (XRD), transmission electron microscopy (TEM), N adsorption–desorption and
2
Copyright: American Scientific Publishers
energy-dispersive X-ray (EDX) techniques. Finally, it was used as a reusable and new catalyst
Delivered by Ingenta
to promote the synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3-d]pyrimidinone derivatives as
important biologically active compounds. Eco-friendly protocol, high yields, short reaction times and
easy and quick isolation of the products are the main advantages of this procedure.
Keywords: PMO,
Nanocatalyst,
Fe O @Ph-PMO-NaHSO .
Tetrahydrobenzo[b]pyran,
Pyrano[2,3-d]pyrimidinone,
3
4
4
1
. INTRODUCTION
post-synthetic grafting method2–4 and remarkable decrease
in the mesostructured arrangement and textural proper-
In recent years, porous materials have played a very
important role in science and industry so that billion dol-
lars are spent annually in the use of these materials in
various fields. Some of these important fields are ionic
exchange, separation, catalysis, preparation of batteries,
fuel cells, sensors and many others. Among these mate-
rials, mesoporous silica has attracted considerable atten-
tion in the field of adsorption and catalysis because of its
uniform pore size, large pore volume, and high surface
5
–6
ties at a high loading level of functional groups.
999, use of periodic mesoporous organosilica materials
as another member of this family has attracted the atten-
In
1
7
–9
tion of research groups. Periodic mesoporous organosil-
ica materials are a class of hybrid materials which in
them organic groups are distributed uniformly inside the
framework, causing properties including mechanical and
hydrothermal stability, diffusion of guest molecule and
lack of pore blocking and they are more hydrophobic
and stable in water than pure organized silicas (MCM-41
or SBA-15). This feature expands the range of applications
in, for example, optical gas sensing, catalysis, chromatog-
1
area. The surface of mesoporous silica can be modified
with various types of organic functional groups, produc-
ing organic–inorganic hybrid materials, in order to use
as a catalyst. Some members of these mesoporous mate-
rials such as MCM-41 and SBA-15 in spite of men-
tioned properties often suffer from pore blocking and
in homogeneous distribution of the functional groups in
1
0–12
raphy, separation and nanotechnology.
For the prepara-
tion of this kind of materials, a common method including
hydrolysis and condensation of a bridged organosilane pre-
ꢀ
ꢀ
ꢀ
cursor of the type (R O) Si–R–Si(OR ) (R is methyl or
3
3
ethyl and R is an organic group) in the presence of a struc-
ture directing agent can be used.
∗
Author to whom correspondence should be addressed.
J. Nanosci. Nanotechnol. 2019, Vol. 19, No. 6
1533-4880/2019/19/3447/012
doi:10.1166/jnn.2019.16032
3447

Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
Shirini et al.
On the other hand, the synthesis of catalysts based on
the principles of green chemistry is very important and it
will be possible by the preparation of nanocatalysts based
on high selectivity and activity and easy separation. Simul-
taneous use of magnetic nanoparticles because of their
easy separation and periodic mesoporous materials with
their unique properties in a single material can be consid-
ered to follow the green chemistry principles.
benzene, sodium bisulfate monohydrate, Pluronic P-123
−1
(M : 5800 g · mol ꢃ, NaOH, benzaldehyde derivatives,
n
1,3-cyclohexanedione, barbituric acid, thiobarbituric acid
and malononitrile were purchased with high purity from
Sigma, Aldrich and Merck Companies. The purity deter-
mination of the substrate and reaction monitoring were
accomplished by TLC on silica-gel polygram SILG/UV
2
54 plates.
The synthesis of natural molecules, pharmaceuti-
cals and biologically active compounds for a long
time has been a significant branch of organic syn-
thesis. Tetrahydrobenzo[b]pyran and pyrano[2,3-d]-
pyrimidinones derivatives belong to important classes
of nitrogen-containing heterocyclic compounds that
show significant pharmaceutical and biological activ-
ities including anticancer, antitumor, antimalarial,
antibacterial, antihypertensive, anti-inflammatory, hep-
atoprotective, cardiotonic, vasodilator, bronchiodila-
tor, antifolate, and antiallergic activities.13–19 Several
synthetic methods have been reported to obtain
more potentially biological derivatives of these com-
2
.2. Characterization Techniques
The crystallinity of the synthesized MNPs were analyzed
by an X-PERT High Score X-ray diffraction (PANaliti-
cal) and measured with Cu Kꢄ radiations in the range
of 0.78–80 (2ꢅꢃ. The quality and composition of the
synthesized nanoparticles were characterized by a Perkin-
Elmer spectrum BX series in the range of 400–4000 cm .
The size and morphology of particles were studied by
a Philips transmission electron microscopy (TEM, CM10
HT 100 kV). Melting points were measured by a Büchi
B-545 apparatus in open capillary tubes. N adsorption–
desorption was measured by a BELSORP-mini II instru-
ment at 77 K. Before using the samples were degassed for
ꢁ
−1
2
2
0
pounds using catalysts such as N-methylimidazole,
2
1
22
24
tetrabutylammonium bromide,
p-dodecylbenzenesulfonic acid, poly(4-vinylpyridine),
trisodium citrate,
ꢁ
2
3
2 h at 120 C. The specific surface area of each material
2
5
26
was calculated using the Brunauer–Emmett Tellet (BET)
method. The EDX characterization of the catalyst was per-
formed on a field emission scanning electron microscope
potassium phthalimide-N-oxyl,
NH H PO /Al O ,
4
2
4
2
28
3
2
7
Na CaP O , NiFe O @SiO @H [NaP W O110] and
2
2
7
2
4
2
14
5
30
silica coated magnetic NiFe O nanoparticles sup-
2
4
ported H PW O (NFS-PWA )I P (: f 4o 6r . 1t h6 e1 . 6s 0y n. 1t h3 e7 s iOs n o: fSun, 17 Mar 2019 02:32:34
making by TE-SCAN Company and equipped with energy
3
12 40
2
9
Copyright: American S cd ii es pn et irf si ci v Pe uX b- lri as yh es pr se ctrometer operating at 15 kV.
tetrahydrobenzo[b]pyrans),
diammonium hydrogen
Delivered by Ingenta
3
0
31
32
phosphate, L-proline, KAl(SO ꢃ · 12H O (alum),
4
2
2
2
1
tetrabutylammonium bromide, sulfonic acid nanoporous
2.3. Preparation of Fe
Fe O -MNPs were chemically synthesized with a little
modification in the methodology already described in the
literature. For the synthesis of Fe O -MNPs, ferric chlo-
O -MNPs
3 4
3
3
34
silica (SBA-Pr-SO H),
nano-sawdust-OSO H,
Al-
3
3
3
4
HMS-20,3 and ZnO-supported copper oxide (for the
5
3
6
37
synthesis of pyrano[2,3-d]-pyrimidinones).
Despite
3
4
undeniable advantages of these methods, most of them
are accompanied with limitations including drastic reac-
ride hexahydrate FeCl ·6H O (11.0 g, 40.7 mmol) and fer-
3
2
rous chloride tetrahydrate FeCl ·4H O (4.0 g, 20.1 mmol)
2
2
3
3
tion conditions, difficulties in the preparation of the
catalyst,34 long reaction times and non-recoverability of
the catalyst. To overcome the drawbacks of these meth-
ods there has been continuous interest to develop easier
methods for the synthesis of tetrahydrobenzo[b]pyran and
pyrano[2,3-d]-pyrimidinones derivatives. In the present
study and in order to develop simple, efficient, and mild
procedures using easily separable and reusable solid cata-
lysts, a new magnetically separable solid acid nanocatalyst
is prepared and applied to the synthesis of tetrahy-
drobenzo[b]pyrans and pyrano[2,3-d]-pyrimidinones. This
strategy involves Fe O nanoparticles as the magnetic core
were dissolved in deionized water (250 mL) under nitro-
35
ꢁ
gen atmosphere with mechanical stirrer at 85 C in order
to prepare the stock solution of ferrous and ferric chlo-
ride. Then the prepared solution was slowly added to
−
1
ꢁ
2
50 mL of a 2 mol L ammonia solution heated at 80 C
under argon gas protection and vigorous stirring. During
the process, the solution temperature was kept constant at
ꢁ
8
0 C and argon gas was purged to prevent the intrusion
of oxygen. After completion of the reaction, the obtained
precipitate of Fe O -MNPs was separated from the reac-
3
4
tion medium by the magnetic field and then was washed
four times with 500 mL double-distilled water. Finally,
the obtained Fe O -MNPs were suspended in 500 mL of
3
4
coated by Ph-PMO as a thin layer on which NaHSO is
4
3
4
adsorbed.
degassed deionized water.
2
2
. EXPERIMENTAL DETAILS
.1. Material
All chemicals including FeCl · 6H O, FeCl · 4H O,
2.4. Preparation of Fe O @Ph-PMO Nanocomposite
3
4
For the synthesis of Fe O @Ph-PMO, 3.3 g Pluronic p123
3 4
(Mn = 5800 g/mol) was dissolved in a mixture of Fe O -
3
2
2
2
3
4
tetraethylorthosilicate (TEOS), 1,4-bis(triethoxysilyl)
MNPs (2 g) and concentrated HCl (0.55 mL) in distilled
3448
J. Nanosci. Nanotechnol. 19, 3447–3458, 2019

Shirini et al.
Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
water (120 mL) under argon gas protection at room tem-
perature. Then, 1,4-bis(triethoxysilyl) benzene (2.3) mL
and tetraethoxysilane (1.5 mL) were added simultaneously
ꢁ
to the mixture dropwise and stirred for 2 hours at 40 C. At
the end of this process, the magnetic composite was kept
ꢁ
at 100 C for 24 h under static conditions. The resultant
solid was filtered, and the template was removed by sol-
vent extraction. For this purpose, the magnetic nanocom-
ꢁ
posite was dispersed in acetone and refluxed at 56 C for
1
0 h, then washed with distilled water and hot ethanol.
This procedure was repeated twice to be sure of removing
of the surfactant.
2
.5. Preparation of Fe O @Ph-PMO-NaHSO
3 4 4
Figure 2. The FT-IR spectra of Fe O @Ph-PMO, before removal of
3
4
Nanocatalyst
the template (a), Fe O @Ph-PMO, after removal of the template (b) and
3
4
3
9
Based on the method of Golshekan et al., Fe O @Ph-
3
4
Fe O @Ph-PMO-NaHSO (c).
3
4
4
PMO-NaHSO was prepared by adding the synthesized
4
mesoporous Fe O @Ph-PMO nanoparticles (1.5 g) to an
3
4
Fe O @Ph-PMO-NaHSO (20 mg) in 3 mL aqueous
3 4 4
ꢁ
aqueous solution of NaHSO ·H O (20 mL, 0.7 g, 5 mmol)
ethanol (1:1) was stirred while heating at 80 C in certain
times. The reaction products were monitored using thin-
layer chromatography (n-hexane:ethylacetate; 7:3). After
completion of the reaction, the mixture was triturated with
ethanol (3 mL). The magnetic nanocomposite was then
separated in the presence of a magnetic stirring bar; the
reaction mixture became clear. The crude product was
recrystallized from ethanol to give the pure product.
4
2
ꢁ
and the mixture was sonicated at 25 C for 1 min. In
continue, the mixture was stirred for 30 min. Finally,
water was removed by decanting and the powder was
ꢁ
dried in an oven at 90 C for 2 h. A brown solid acid
formulated as Fe O @ph-PMO-NaHSO was obtained.
3
4
4
Schematic preparation of Fe O @ph-PMO-NaHSO is
3
4
4
shown in Figure 1.
IP: 46.161.60.137 On: Sun, 17 Mar 2019 02:32:34
2
.6. General Procedure for the Synthesis of
2.7. General Procedure for the Synthesis of
Copyright: American Scientific Publishers
Tetrahydrobenzo[b]pyran Derivatives
Delivered by Ing eP ny tra ano[2,3-d]pyrimidinone Derivatives
A mixture of an aromatic aldehyde (1 mmol), mal-
ononitrile (1 mmol), dimedone (1.0 mmol), and
Fe O @Ph-PMO-NaHSO (30 mg) was added to a
mixture of aromatic aldehyde (1 mmol), malononitrile
3 4 4
Con. HCl/ H O
2
40 ºC, 2 h
TEOS
+
Pluronic p123
(
EtO) Si
Si(OEt)3
3
Fe O
3
4
Removal of template
NaHSO .H O
4
2
room tempreture
NaHSO4
(EtO) Si
3
Si(OEt)3
Figure 1. Preparation of Fe O @Ph-PMO-NaHSO .
3
4
4
J. Nanosci. Nanotechnol. 19, 3447–3458, 2019
3449

Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
Shirini et al.
Table I. Structural parameters of the synthesized Fe O @Ph-PMO, and
3
4
Fe O @Ph-PMO-NaHSO .
3
4
4
2
−1
3
SBET (m ·g
ꢃ
V (cm ·g)
Fe O @Ph-PMO
357ꢆ83
163ꢆ5
0.5154
0.3093
3
4
Fe O @Ph-PMO-NaHSO
3
4
4
Notes: SBET: Specific surface area; V : Total pore volume at relative pressure 0.99.
d (ppm) 5.06 (s, 1H), 7.34 (s, 2H), 7.48 (dt, J = 7.6 Hz,
1
J = 1.6 Hz, 1H), 7.54 (dd, J = 8 Hz, J = 1.2 Hz, 1H),
2
1
2
7
8
.67 (dt, J = 7.6 Hz, J = 1.2 Hz, 1H), 7.86 (dd, J =
1
2
1
Hz, J = 1.2 Hz, 1H), 12.43 (NH, s, 1H), 13.67 (NH,
2
1
3
s, 1H); C NMR (100 MHz, DMSO-d ꢃ: d (ppm) 30.7,
6
5
1
6.9, 93.4, 119.0, 124.2, 128.6, 131.5, 133.9, 138.0, 149.7,
52.1, 158.6, 160.7, 174.4.
3
. RESULTS AND DISCUSSION
3
.1. FT-IR Analysis
Figure 2 shows the FT-IR spectra of the synthesized
Fe O @Ph-PMO (before and after removal of the tem-
3
4
Figure 3. The XRD spectra of Fe O @Ph-PMO after removal of the
template.
3
4
plate) and Fe O @Ph-PMO-NaHSO MNPs, respectively.
3
4
4
Before removal of the template (Fig. 2(a)), the FT-IR spec-
tra showed high-intensity peaks for the CH stretching
2
(
1 mmol) and barbituric or thiobarbituric acid (1 mmol)
−1
modes located at ∼2870 and 2970 cm (symmetric and
ꢁ
in water (3 mL). Then the mixture was heated at 80 C
in appropriate times and the progress of the reaction was
asymmetric), as well as for the CH bending mode at
2
−1
∼
1473 cm . These peaks are related to the surfactant
tail and their intensities represent to the surfactant con-
centration. The absence of CH peaks in Figure 2(b), con-
firms the surfactant removal. Two intense bands at 525
indicated by TLC (n-hexane:ethy lI Pa c: e4 t 6a t. e1 ;6 31 : .76) 0. W. 1 3i t 7h Oc o nm: -S un, 17 Mar 2019 02:32:34
Copyright: American Scientific Publishers
pleting the reaction, 3 ml ethanol was poured and the mag-
2
Delivered by Ingenta
netic nanocomposite was separated in the presence of a
magnetic stirring bar; the reaction mixture became clear
and the crude product was recrystallized from ethanol to
give the pure product. The pure products were character-
ized by conventional spectroscopic methods. Physical and
spectral data for selected compound are represented below.
−1
and 1648 cm are attributed to the Si–C and asymmet-
ric phenylene (C C) stretching modes, respectively. The
−1
peaks at 1159 and 2891 cm are attributed to the bridg-
ing phenyl C–H vibration and stretching, respectively. The
−1
sharp band at 1075 cm from Si–O stretching confirms
−1
the formation of siloxane bonds. The band at 3435 cm
is from the Si–OH groups. Fe O usually presents bands
2
.7.1. 7-Amino-5-(2-nitrophenyl)-4-Oxo-2-Thioxo-
,3,4,5-Tetrahydro-2H-Pyrano[2,3-d]pyrimidine-6-
3
4
−1
1
at ∼570 and 430 cm , due to the Fe-O vibrations in
Carbonitrile (8e)
tetrahedral and octahedral sites, respectively. The sulfonic
ꢁ
−1
Mp = 242–246 C; IR (KBr) v /cm : 3426, 3062, 2197,
acid bonds can be observed at ∼1200–1250, 1010–1100
max
1
−1
1
675, 1573, 1518, 1349; H NMR (400 MHz, DMSO-d ꢃ:
and 650 cm , which are attributed to the O
S
O
6
Figure 4. N adsorption–desorption of Fe O @Ph-PMO (a), and Fe O @Ph-PMO-NaHSO (b).
2
3
4
3
4
4
3450
J. Nanosci. Nanotechnol. 19, 3447–3458, 2019

Shirini et al.
Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
Table III. Optimization of the amounts of the catalyst, temperature
and solvent in the synthesis of pyrano[2,3-d]-pyrimidinone derivative of
4-chlorobenzaldehyde.
Amount
of catalyst
Temp.
( C)
Time
(min)
Conversion
(Yield %)
ꢁ
a
Entry
(g)
Solvent
1
2
3
4
5
6
7
0.02
0.02
0.02
0.02
0.02
0.02
0.02
CH Cl2
r.t.
Reflux
r.t.
Reflux
r.t.
120
120
120
120
120
120
120
Trace
Trace
Trace
Trace
Trace
Not
2
CH Cl2
2
CH CN
3
CH CN
3
C H OH
2
5
C H OH
Reflux
80
2
5
–
Not
Figure 5. The TEM image of Fe O @Ph-PMO-NaHSO .
3
4
4
completed
100(90)
100(95)
100(80)
Trace
8
9
0.02
0.03
0.01
–
H O
80
80
80
80
16
8
20
2
H O
2
10
1
C H OH:H O (1:1)
2
5
2
1
H O
120
2
a
Note: Isolated yields.
3
.2. X-ray Diffraction (XRD) Analysis
Figure 3 shows the powder X-ray diffraction (XRD) pat-
tern of the synthesized Fe O @Ph-PMO. The peak at
3
4
3
8
2
theta near 0.9 is related to (d100) hexagonal structures.
The peaks at 10 < 2ꢅ < 80 from Fe O @Ph-PMO could
3
4
be confirmed the presence of MNPs. The MNPs indi-
ꢁ
ꢁ
ꢁ
ꢁ
cated peaks with 2 theta at 30.06 , 35.67 , 43.47 , 53.83 ,
5
ꢁ
ꢁ
7.36 and 62.96 which is quite identical to pure mag-
Figure 6. EDX analysis of Fe O @Ph-PMO-NaHSO .
3
4
4
netite and matched well with the XRD pattern of the stan-
IP: 46.161.60.137 On: Sun, 17 Mar 2019 02:32:34
Copyright: American S dc ai er dn t Fi f iec OP u bf rl oi smh eJ ros int Committee on Powder Diffraction
3
4
4
0
Delivered byS It na ng de an r tda s (JCPDS No. 19-692). The XRD measurements
asymmetric and symmetric stretching vibrations and S–O
stretching vibration of SO H groups, respectively. How-
of Fe O @Ph-PMO was carried out to confirm the pres-
3 4
3
ever, in the FT-IR spectra of the synthesized nanoparticles,
such bands could not be observed because they are prob-
ence of magnetic nanoparticles in the cave of the synthe-
sized nanocomposite. The same peaks were observed in
both bare and periodic mesoporous coated MNPs, indicat-
ing the accurate synthesis of the Fe O @Ph-PMO MNPs.
ably overlapped by the bands of SiO . On the other hand,
2
−
1
the band at ∼3360 cm became much broader. The broad
3
4
−
1
peak at 3000–3500 cm is correlated to OH groups of
NaHSO and Si–OH groups.
3.3. BET Analysis
4
The results of N2 adsorption–desorption isotherms of
Fe O @Ph-PMO and Fe O @Ph-PMO-NaHSO were
3
4
3
4
4
Table II. Optimization of the amount of the catalyst, temperature
and solvent in the synthesis of tetrahydrobenzo[b]pyran derivative of
4
-chlorobenzaldehyde.
O
Ar
Fe O @Ph-PMO–NaHSO
O
O
3
4
4
CN
O
CN
(
0.02 g)
Amount
of catalyst
+
+
Me
Temp.
( C)
Time
(min)
Conversion
(Yield %)
Ar
H
CN
(2)
C H OH:H O (1:1), 80 °C
O
NH2
ꢁ
a
Me
Me
2
5
2
Me
Entry
(g)
Solvent
(
4a-q)
(
1)
(3)
1
2
3
4
5
0.02
0.02
0.02
0.02
0.02
CH Cl2
r.t.
Reflux
r.t.
Reflux
r.t.
90
90
90
90
90
Trace
Trace
Trace
Trace
2
Scheme 1. Synthesis of tetrahydrobenzo[b]pyran derivatives catalyzed
by Fe @Ph-PMO-NaHSO in aqueous ethanol (1:1) under thermal
condition.
CH C
2
l2
CH CN
3
O
4
4
3
CH CN
3
H O
Not
2
completed
100(80)
100(90)
100(98)
100(90)
100(80)
100(90)
6
7
8
9
0.02
0.02
0.02
0.01
0.02
0.03
H O
80
80
80
80
80
80
90
24
10
36
25
20
2
C H OH
2
5
C H OH:H O (1:1)
2
5
2
C H OH:H O (1:1)
2
5
2
10
1
–
1
C H OH:H O (1:1)
2
5
2
Scheme 2. Synthesis of pyrano[2,3-d]-pyrimidinone derivatives cat-
Note: aIsolated yields.
alyzed by Fe O @Ph-PMO-NaHSO in water under thermal conditions.
3
4
4
J. Nanosci. Nanotechnol. 19, 3447–3458, 2019
3451

Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
Shirini et al.
Table IV. Preparation of tetrahydrobenzo[b]pyran and pyrano[2,3-d]-pyrimidinone derivatives by using Fe O @Ph-PMO-NaHSO as the catalyst.
3
4
4
ꢁ
M.P. ( C)
a
Entry
1
Aldehyde
C H CHO
Product
Time (min)
4a
Yield (%)
9
Found
Reported
227–229
Ref.
[41]
95
98
227–229
6
5
2
3
4-ClC H CHO
4b
4c
12
15
211–212
234–236
210–212
235–237
[42]
[42]
6
4
3-ClC H CHO
93
6
4
4
5
2-ClC H CHO
4d
4e
15
9
95
97
219–220
204–206
218–220
203–205
[21]
[21]
6
4
4-BrC H CHO
6
4
6
7
4-FC H CHO
4f
10
90
171–174
179–180
211–213
176–178
177–178
212–214
[42]
[20]
[21]
6
4
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Copyright: American Scientific Publishers
Delivered by Ingenta
4-NO C H CHO
4g
4h
8
6
95
90
2
6
4
8
9
3-NO C H CHO
2 6 4
2-NO C H CHO
4i
4j
8
90
93
213–217
202–205
215–217
204–205
[21]
[20]
2
6
4
1
0
1
4-OHC H CHO
35
6
4
1
4-MeOC H CHO
4k
39
90
200–203
199–201
[21]
6
4
3452
J. Nanosci. Nanotechnol. 19, 3447–3458, 2019

Shirini et al.
Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
Table IV. Continued.
ꢁ
M.P. ( C)
a
Entry
Aldehyde
4-MeC H CHO
Product
Time (min)
4m
Yield (%)
20
Found
Reported
214–216
Ref.
[23]
12
90
211–214
6
4
1
3
4
4-NMe C H CHO
4n
4o
35
45
85
92
199–203
255–257
198–200
258–260
[45]
[43]
2
6
4
1
2-Naphthaldehyde
1
5
6
4-CHOC H CHO
4p
4q
20
25
90
85
264–266
243–244
266–268
243–244
[44]
[44]
6
4
1
3-CHOC H CHO
6
4
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Copyright: American Scientific Publishers
Delivered by Ingenta
1
7
8
C H CHO
7a
30
90
214–216
238–240
215–217
242–243
[35]
[35]
6
5
1
4-ClC H CHO
7b
8
95
6
4
19
3-ClC H CHO
7c
14
93
238–240
240–241
[34]
6
4
2
0
1
2-ClC H CHO
7d
7e
4
95
95
212–213
227–230
212–214
230–231
[34]
[30]
6
4
2
4-BrC H CHO
10
6
4
J. Nanosci. Nanotechnol. 19, 3447–3458, 2019
3453

Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
Table IV. Continued.
Shirini et al.
ꢁ
M.P. ( C)
Reported
a
Entry
Aldehyde
Product
Time (min)
7f
Yield (%)
20
Found
Ref.
[36]
22
4-FC H CHO
80
85
264–266
268–270
238–240
6
4
23
4-NO C H CHO
7g
4
237–239
[36]
2
6
4
2
4
5
3-NO C H CHO
7h
7i
25
40
85
90
268–270
267–269
335–337
[46]
[45]
2
6
4
2
4-CHOC H CHO
>300
6
4
IP: 46.161.60.137 On: Sun, 17 Mar 2019 02:32:34
Copyright: American Scientific Publishers
2
6
7
C H CHO
Deliver e8 ad by Ingenta20
85
220–224
224–225
[35]
[35]
6
5
2
4-ClC H CHO
8b
30
90
>300
>300
6
4
b
28
29
30
4-BrC H CHO
8c
8d
8e
35
40
42
85
83
84
235(dec.)
233–235
242–245
236(dec.)
235–236
242–246
[30]
[30]
[49]
6
4
4-NO C H CHO
2
6
4
2-NO C H CHO
2
6
4
Notes: aIsolated yields. bDecomposition.
3454
J. Nanosci. Nanotechnol. 19, 3447–3458, 2019

Shirini et al.
Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
3
.5. EDX Analysis
The energy-dispersive Xray analysis (EDX) analysis
Fig. 6) of the catalyst showed the presence of Fe, Si, Na,
(
S, O, and C elements in the expected nanocatalyst.
+
3
.6. H Content Determination
+
The amount of exchangeable H was determined by neu-
tralization titration. For this purpose, 0.02 g Fe O @Ph-
3
4
PMO-NaHSO was dispersed in 10 mL of NaCl solution
4
(
0.1 M) and stirred for 30 minutes then the mixture was
titrated with NaOH (0.02 M) in the presence of phenolph-
thalein as indicator. The amounts of acidic protons were
−1
found to be 0.8 mmol · g . This result confirms the syn-
thesis of nanocatalyst and acting it as a solid acid catalyst.
3
.7. Catalytic Activity
Figure 7. Photographs of an aqueous suspension of Fe O @Ph-PMO-
3
4
The above mentioned structural analysis results directed us
to assume that Fe O @Ph-PMO-NaHSO may be able to
NaHSO before (a) and after (b) magnetic capture.
4
3
4
4
promote the organic transformations which need the acidic
catalysts to speed-up. In order to confirm this assumption
the promoting ability of this reagent was studied in the
preparation of tetrahydrobenzo[b]pyran and pyrano [2,3-
d]-pyrimidinone derivatives. To prepare these compounds,
the reaction of 4-chlorobenzaldehyde (1.0 mmol), mal-
ononitrile (1.0 mmol), and dimedone (1.0 mmol) or bar-
bituric acid (1.0 mmol) was selected as a model system.
Then the effect of the amounts of the catalyst, temper-
ature, and solvent for the more efficient conditions was
investigated and the obtained results were arranged in
Tables II and III. After the selection of the best conditions,
as indicated in Schemes 1 and 2, a wide range of aromatic
aldehydes were subjected to react with malononitrile and
1,3-cyclohexanedione or barbituric acid in the presence of
Fe O @Ph-PMO-NaHSO to generate the requested prod-
shown in Figure 4. From N adsorption–desorption analy-
2
sis of samples, a type IV BET isotherm for both samples
was obtained, as shown in Figure 4, which is attributed
3
8
to mesoporous structures. The Brunauer-Emmet-Teller
BET) surface areas and total pore volume of Fe O @Ph-
(
3
4
2
−1
3
PMO were 357.83 m · g and 0.5154 cm · g, respec-
tively. The BET surface area and total pore volume of
Fe O @Ph-PMO-NaHSO decreased which proves the
3
4
4
IP: 46.161.60.137 On: Sun, 17 Mar 2019 02:32:34
adsorption of NaHSO on the surface and successful syn-
4
Copyright: American Scientific Publishers
thesis of the nanocatalyst. Table I summarizes the struc-
Delivered by Ingenta
tural parameters obtained from N adsorption–desorption.
2
3
.4. TEM Analysis
Figure 5 shows TEM image of the synthesized Fe O @Ph-
3
4
PMO-NaHSO . The TEM image revealed that all samples
4
3
4
4
were spherical-like particles. Based on the TEM images,
analysis of the Fe O @Ph-PMO-NaHSO surface mor-
phology demonstrated that the aggregation of the particles
is uniform and the size of them is up to 15 nm.
ucts and the results were summarized in Table IV. Also,
the reactions were checked by aliphatic aldehydes that lead
to a mixture of unidentified products. So the method is
not useful for these types of compounds. It is important
3
4
4
Table V. Catalytic activity and reaction conditions comparison of Fe O @Ph-PMO-NaHSO with other reported catalysts in the synthesis of 4b and
3
4
4
7e products.
Time (min) Yield (%) TOF (s 1ꢃc
−
Ref.
Entry
Catalyst
Amount
Condition
ꢁ
1
2
3
4
5
6
7
8
9
KAl(SO ꢃ ·12H O (alum)
(0.1 mol)
(0.1 mol)
0.1 g
H O/80 C
40
30
180
240
60
12
120
90
30
30
20
10
93
95
90
69
86
98
81
75
85
95
61
95
0ꢆ0008
0ꢆ0016
0ꢆ083
0ꢆ037
0ꢆ796
6ꢆ8
0ꢆ0009
0ꢆ0024
0ꢆ0009
0ꢆ0016
2ꢆ541
5ꢆ278
[32]
[42]
[47]
[23]
[48]
4
2
2
2
Tetrabutylammonium bromide
C H OH/reflux
H O: C H OH (1:1)/reflux
H O/reflux
H O: C H OH (1:1)/reflux
H O: C H OH (1:1)/reflux
H O: C H OH (1:1)/r.t.
2
5
Na SeO4
2
2
2
5
a
−4
p-Dodecylbenzenesulfonic acid
(4×10 mol)
2
Fe O -SiO -Met
0.03 g
0.02 g
3
4
2
2
2
5
Fe O @Ph-PMO-NaHSO
[This work]
[30]
3
4
4
2
2
5
b
Diammonium hydrogen phosphate
(0.1 mol)
(0.05 mol)
(0.1 mol)
(0.1 mol)
0.02 g
2
2
5
b
L-Proline
H O: C H OH (1:1)/r.t.
[31]
[32]
[21]
[29]
2
2
5
ꢁ
KAl(SO ꢃ ·12H O (alum)
H O/80 C
4
2
2
2
10
11
12
Tetrabutylammonium bromide
H O/reflux
2
ꢁ
SBA-Pr-SO H
Neat/140 C
3
ꢁ
Fe O @Ph-PMO-NaHSO
0.03 g
H O/80 C
[This work]
3
4
4
2
Notes: aAldehyde (1 mmol), dimedone (1 mmol) and malononitrile (1.1 mmol) were used in this method. bIn this method, ratio of aldehyde (mmol): barbituric acid (mmol):
malononitrile (mmol): is 1:1:1.2. cThe amounts of catalysts in TOF were calculated in term of gram of catalysts for all mentioned catalysts in the table.
J. Nanosci. Nanotechnol. 19, 3447–3458, 2019
3455

Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
Shirini et al.
Scheme 3. Plausible mechanism for the preparation of tetrahydrobenzo[b]pyran (4) and pyrano [2,3-d]-pyrimidinone (7 and 8) derivatives.
IP: 46.161.60.137 On: Sun, 17 Mar 2019 02:32:34
to note that the superparamagnetic property of the syn-
cyclo condensation and dehydration to produce the corre-
sponding product.
Copyright: American Scientific Publishers
thesized nanocatalyst made the separation and reuse of
Delivered by Ingenta
this catalyst very easy. Figure 7 shows the separation of
this nanocatalyst from its aqueous dispersion within a few
minutes.
3.8. Reusability of the Catalyst
The recovery ability of Fe O @Ph-PMO-NaHSO was
3
4
4
To demonstrate the worthiness of the prepared catalyst,
the results obtained from the synthesis of 2-amino-4-
measured in the synthesis of 7-amino-6-cyano-5-(4-
chlorophenyl)-5H-pyrano[2,3-d]pyrimidinone (7b) and in
the synthesis of 2-amino-4-(4-chlorophenyl)-7,7-dimethyl-
5-oxo-5,6,7,8 tetrahydro-4H chromene-3-carbonitrile (4b)
under optimized reaction conditions. After completion of
the reaction and separation of the catalyst from the reaction
(
4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-
4
7
2
H-chromene-3-carbonitrile (4b) (Entry 2, Table IV) and
-amino-5-(4-bromophenyl)-2,4-dioxo-1,3,4,5-tetrahydro-
H-pyrano[2,3-d]pyrimidine-6-carbonitrile (7e) (Entry 21,
Table IV) using this method is compared with the
selected catalysts in Table V. This comparison shows the
effectiveness of the heterogeneous catalyst Fe O @Ph-
3
4
PMO-NaHSO in increasing of the rate and yield of the
4
reaction. The turnover frequency (TOF) was calculated
and the higher amount of it displays the better perfor-
mance of the prepared catalyst in comparison with others
as shown in Table V. On the other hand, the catalyst can
be easily separated using an external magnetic field, and
the reaction proceeds under mild conditions.
A suggested mechanism for the studied reactions is
shown in Scheme 3. According to this mechanism, the
Fe O @Ph-PMO-NaHSO catalyst activates the carbonyl
3
4
4
of the aromatic aldehyde to produce the intermediate (b).
In continue, this intermediate reacts with beta-diketone
to give the intermediate (c). This intermediate undergoes
Figure 8. Reusability of Fe O @Ph-PMO-NaHSO in the synthe-
sis of 2-amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile (4b).
3
4
4
3456
J. Nanosci. Nanotechnol. 19, 3447–3458, 2019

Shirini et al.
Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
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. L. Mercier and T. J. Pinnavaia, Chem. Mater. 12, 188 (2000).
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0. F. Goethals, B. Meeus, A. Verberckmoes, P. Van der Voort, and
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pyrano[2,3-d]pyrimidine-6-carbonitrile (7b).
3
4
4
(
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air, and reused with the least change in the reaction time
and yield even after five cycles of the synthesis of the
product (Figs. 8 and 9). The amount of the acidic pro-
tons for both fresh and the recycled catalyst after fifth
run was measured by the neutralization titration as men-
tioned before. According to this, the amount of acidic
protons was changed from 0.8 mmol/g for fresh catalyst
to 0.6 mmol/g for recycled catalyst, whereas this factor
was 0.2 mmol/g for Fe O @Ph-PMO, which showed that
1
1
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4
1
although washing with water/ethanol leached out a small
2
IP: 46.161.60.137 On: Sun, 17 Mar 2019 02:32:34
amount of NaHSO , due to its highly solubility, the prod-
4
(2010).
Copyright: American Scientific Publishers
ucts were obtained in least change in reaction times and
yields.
22. J. Azizian, A. Shameli, S. Balalaie, M. M. Ghanbari,
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2
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In conclusion, Fe O @Ph-PMO-NaHSO as a new
3
4
4
5, 1089 (2013).
nanocatalyst was successfully synthesized and utilized
as an efficient catalyst for the preparation of tetrahy-
drobenzo[b]pyran and pyrano[2,3-d]-pyrimidinone deriva-
tives under mild conditions. This catalyst is thermally
stable, green, recyclable, inexpensive and easy to prepare.
In addition, it can be easily separated from the reaction
mixture and recovered up to five times without any sig-
nificant influence on its activity or the reaction yield. The
operational simplicity, high yields, and easy work-up pro-
cedure associated with this catalytic process give it advan-
tages over the other methods.
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J. Nanosci. Nanotechnol. 19, 3447–3458, 2019
3457

Synthesis of Tetrahydrobenzo[b]pyran and Pyranoꢀ2ꢁ3-dꢂpyrimidinone Derivatives
Shirini et al.
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J. Nanosci. Nanotechnol. 19, 3447–3458, 2019