Butane-1-sulfonic acid immobilized on magnetic Fe3O4@SiO2 nanoparticles: A novel and heterogeneous catalyst for the one-pot synthesis of barbituric acid and pyrano[2,3-d] pyrimidine derivatives in aqueous media

Article abstract of DOI:10.1002/aoc.4455

Butane-1-sulfonic acid immobilized on magnetic Fe₃O₄@SiO₂ nanoparticles (Fe₃O₄@SiO₂-Sultone) was easily prepared via direct ring opening of 1,4-butanesultone with nanomagnetic Fe₃O₄@SiO₂. The prepared reagent was characterized and used for the efficient promotion of the synthesis of barbituric acid and pyrano[2,3-d] pyrimidine derivatives. All reactions were performed under mild and completely heterogeneous reaction conditions affording products in good to high yields. The catalyst is easily isolated from the reaction mixture by magnetic decantation and can be reused at least eight times without significant loss in activity.

Full text of DOI:10.1002/aoc.4455

Received: 27 March 2018
DOI: 10.1002/aoc.4455
Revised: 7 May 2018
Accepted: 12 May 2018
F U L L P A P E R
Butane‐1‐sulfonic acid immobilized on magnetic
Fe3O4@SiO2 nanoparticles: A novel and heterogeneous
catalyst for the one‐pot synthesis of barbituric acid and
pyrano[2,3‐d] pyrimidine derivatives in aqueous media
M. Pourghasemi‐Lati1 | F. Shirini2
| M. Alinia‐Asli1 | M.A. Rezvani1
1 University of Zanjan, Department of
Butane‐1‐sulfonic acid immobilized on magnetic Fe3O4@SiO2 nanoparticles
(Fe3O4@SiO2‐Sultone) was easily prepared via direct ring opening of 1,4‐
butanesultone with nanomagnetic Fe3O4@SiO2. The prepared reagent was
characterized and used for the efficient promotion of the synthesis of barbituric
acid and pyrano[2,3‐d] pyrimidine derivatives. All reactions were performed
under mild and completely heterogeneous reaction conditions affording prod-
ucts in good to high yields. The catalyst is easily isolated from the reaction mix-
ture by magnetic decantation and can be reused at least eight times without
significant loss in activity.
Chemistry, College of Science, Zanjan
45195‐313, Iran
2 University of Guilan, Department of
Chemistry, College of Science, Rasht
41335, Iran
Correspondence
F. Shirini, Department of Chemistry,
College of Science, University of Guilan,
Rasht 41335, Iran.
Email: shirini@guilan.ac.ir
M. Alinia‐Asli, Department of Chemistry,
College of Science, University of Zanjan,
Zanjan 45195‐313, Iran.
KEYWORDS
aqueous media, barbituric acid, heterogeneous catalyst, magnetite nanoparticles, pyrano[2,3‐d]
Email: m_aliniaaslir@znu.ac.ir
pyrimidines
1 | INTRODUCTION
Sulfonation using this reagent leads to organic–inorganic
hybrid materials that have been applied as impressive
In recent years the use of magnetic nanoparticles (MNPs)
for the preparation of supported heterogeneous catalysts
has attracted significant attention.[1–12] This attention
can be attributed to the unique properties of these types
of compounds including high thermal and mechanical
stability, large surface area to volume ratio, low toxicity,
ease of recovery by use of an external magnetic field
and well‐defined pore size distribution.[13] In this regard
magnetic metal oxide nanoparticles and especially Fe3O4
nanoparticles have been the focus of much research
recently. This is because, among other advantages, the
existence of many hydroxyl groups on the surface of
solid acid catalysts in organic transformations, a useful
way to combine the advantageous characteristics of
homogeneous protic acids and solid properties.[14]
Arylidene barbituric acids, as important heterocyclic
compounds, can be obtained via the Knoevenagel
condensation reaction between barbituric acid and its
derivatives with aldehydes or ketones that do not contain
α‐hydrogen. For this purpose, a variety of catalysts and
reagents have been used to facilitate this reaction
including CuO nanoparticles,[15] BiCl3,[16] [DABCO]
(SO3H)2Cl2,[17] Ce1MgxZr1 − xO2,[18] ZnO,[19] CoFe2O4,[20]
SiO2 ⋅12WO3 ⋅24H2O,[21] NH2SO3H[22] and K2NiP2O7.[23]
The various biological properties of pyrano[2,3‐d]
pyrimidine derivatives[24–26] cause wide interest in the
preparation of these compounds. For this reason a variety
of methods using various catalysts such as Zn[(L)pro-
line]2,[27] DAHP,[28] SBA‐Pr‐SO3H,[29] L‐proline,[30]
[BMIm]BF4,[31] N‐methylmorpholine,[32] 1,4‐dioxane,[33]
Fe3O4 MNPs leads to
a reaction with tetraethyl
orthosilicate (TEOS) to form Si─ O bonds and to provide
reaction sites for further functionalization of Fe3O4@SiO2
MNPs. Among various types of reagents that can be used
for the functionalization of the surface of solid supports,
1,4‐butanesultone is one of the most important.
Appl Organometal Chem. 2018;e4455.
wileyonlinelibrary.com/journal/aoc
© 2018 John Wiley & Sons, Ltd.
1 of 11
https://doi.org/10.1002/aoc.4455

2 of 11
POURGHASEMI‐LATI ET AL.
[34]
H14[NaP5W30O110
]
and [KAl (SO4)2][35] have been
Subsequently, the prepared Fe3O4 MNPs (4 g) were
dispersed in a mixture of deionized water (48 ml) and
ethanol (180 ml) by ultrasonication for 30 min. Then,
ammonia (4.0 ml, 25%) and TEOS (2.4 ml) were charged
to the reaction dish. After stirring at room temperature
for 12 h, the silica‐coated nanoparticles (Fe3O4@SiO2‐
MNPs) were collected using a permanent magnet
followed by washing three times with ethanol and diethyl
ether and dried at 40 °C in vacuum for 24 h.
The sulfonation of the MNPs was conducted using the
reaction of Fe3O4@SiO2‐MNPs with 1,4‐butanesultone.
For this purpose, Fe3O4@SiO2‐MNPs (4 g) were
suspended in 100 ml of dry toluene containing 1,4‐
butanesultone (2.4 ml), and the colloidal solution was
refluxed for 48 h to yield a magnetically separable
reagent, namely butane‐1‐sulfonic acid immobilized on
Fe3O4@SiO2‐MNPs (Fe3O4@SiO2‐Sultone), which was
isolated and purified as described for Fe3O4@SiO2‐MNPs
(Scheme 1).
reported for this purpose.
Although the methods mentioned above were accom-
panied by some improvements, most of them suffer from
disadvantages such as harsh reaction conditions, use of
harmful organic solvents, long reaction times, tedious
work‐up procedure, use of expensive and moisture‐
sensitive
reagents,
strongly
acidic
conditions,
unsatisfactory yields, non‐recoverability of the catalyst
and environmental pollution. Thus, it is important to find
more efficient catalysts and methods for the synthesis of
arylidine barbituric acids and pyrano[2,3‐d] pyrimidine
derivatives.
2 | EXPERIMENTAL
2.1 | Chemicals
All chemicals, including iron (II) chloride tetrahydrate
(99%), iron (III) chloride hexahydrate (98%) and aldehyde
derivatives, were purchased from Merck or Fluka and were
used without further purification. Water and other solvents
were distilled before use. Yields refer to isolated products.
The products were characterized by their physical
constants, comparison with authentic samples and using
FT‐IR, 1H NMR and 13C NMR spectroscopies. Determina-
tion of the purity of the substrates and reaction monitoring
were accomplished using TLC with silica‐gel Polygram
SILG/UV 254 plates. The FT‐IR spectra were obtained with
a VERTEX 70 (Bruker, Germany). Thermogravimetric
analysis (TGA) was performed with a TG/DTA6300 (All‐
Nanotechnology Company, Japan). Samples were heated
from 25 to 700 °C at 10 °C min−1 under nitrogen atmo-
sphere. Scanning election microscopy (SEM) was con-
ducted with a Philips XL30. Wide‐angle X‐ray diffraction
(XRD) measurements were performed at room temperature
with a Siemens D‐500 X‐ray diffractometer (Germany),
using Ni‐filtered Co‐Kα radiation (λ = 0.15418 nm). The
surface morphologies were characterized using atomic
force microscopy (Ara Nanoscope, Iran).
2.3 | Catalytic Activity
2.3.1 | General procedure for preparation
of 5‐arylidine barbituric acids
Aldehyde (1.0 mmol), barbituric acid (1.0 mmol) and
Fe3O4@SiO2‐Sultone (25 mg) were added to a 25 ml
round‐bottomed flask in water and the resulting mixture
was stirred at room temperature for the appropriate time.
After completion of the reaction (monitored by TLC:
n‐hexane–ethyl acetate, 7:3), water was evaporated and
the product dissolved in warm ethanol (5 ml). The
catalyst was then separated using an external magnet.
The solvent (ethanol) was evaporated to afford the pure
product. If needed, for further purification, the product
can be recrystallized from ethanol.
2.3.2 | General procedure for preparation
of pyrano[2,3‐d] pyrimidine derivatives
A mixture of aromatic aldehyde (1.0 mmol), barbituric
acid (1.0 mmol), malononitrile (1.0 mmol) and
Fe3O4@SiO2‐Sultone (25 mg) in water was stirred at
60 °C for the appropriate time. After completion of the
reaction, water was evaporated, ethanol (5 ml) was added
and the mixture was warmed to dissolve the product.
2.2 | Catalyst Preparation
Firstly, Fe3O4 MNPs approximately 9–11 nm in size were
synthesized using a reported chemical co‐precipitation
technique.[36]
SCHEME 1 Preparation of Fe3O4@SiO2‐Sultone

POURGHASEMI‐LATI ET AL.
3 of 11
Then the catalyst was separated using an external mag-
net. The solvent (ethanol) was evaporated to afford the
pure product. If needed, for further purification, the prod-
uct can be recrystallized from ethanol.
2.4.5 | Ethyl‐7‐amino‐5‐(4‐chlorophenyl)‐
2,4‐dioxo‐1,3,4,5‐tetrahydro‐2H‐pyrano[2,3‐
d]pyrimidine‐6‐carboxylate (5n)
FT‐IR (KBr, νmax, cm−1): 3311, 3188, 3091, 2228, 1899,
1
1648, 1543. H NMR (400 MHz, DMSO, δ, ppm): 2.17
(3H, s, CH3), 4.8 (2H, s, CH2), 5.28 (s, 1H, H‐5) 4.11
(2H, s, CH2), 2.29 (3H, s, CH3), 7.28 (m, H─ Ar), 7.38
(m, 2H, H─ Ar), 7.75 (s, 2H, NH2), 10.99 (s, 1H, NH),
11.55 (s, 1H, NH). 13C NMR (CDCl3, δ, ppm): 88.3, 98.5,
114.8, 126.9, 128.8, 129.0, 129.9, 130.5, 135.9, 150.1,
155.4, 155.8, 159.7, 160.9. MS: (M+) m/z, 313, 278, 188,
153, 111, 77, 57, 43.
2.4 | Spectroscopic Data
2.4.1 | 5(4‐Cl‐Benzylidene) barbituric acid
(4b)
FT‐IR (KBr, νmax, cm−1): 3404, 3214, 2970, 1755, 1703,
1
1570. H NMR (DMSO, δ, ppm): 7.53 (d, 2H, Ar─ H),
8.08 (2d, 2H, Ar─ H), 8.25 (s, 1H, HC═ C), 11.25 (s, H,
NH), 11.40 (s, 1H, NH). 13C NMR (CDCl3, δ, ppm):
117.46, 127.76, 128.29, 133.25, 133.50, 148.70, 150.16,
165.10. EI‐MS: m/z (%) 250 (M+).
2.4.6 | Ethyl‐7‐amino‐5‐(4‐
methoxyphenyl)‐2,4‐dioxo‐1,3,4,5‐
tetrahydro‐2H‐pyrano[2,3‐d]pyrimidine‐6‐
carboxylate (5p)
FT‐IR (KBr, νmax, cm−1): 3413, 3278, 2239, 2165, 1878,
1662, 1543. 1H NMR (400 MHz, DMSO‐d6, δ, ppm):
3.32 (s, 3H, OCH3), 4.41 (1H, s, H‐5), 3.71 (s, 2H, CH2),
2.49 (s, 3H, CH3) 6.93 (m, 2H, H─ Ar), 7.65 (m, 2H,
H─ Ar), 9.07 (2H, br, s, NH2), 11.09–10.03 (s, br, 2H,
NH). 13C NMR (100 MHz, DMSO‐d6, δ, ppm): 33.03,
37.2, 55.8, 75.6, 114.2, 130.1, 134.1, 143.9, 150.5, 157.2,
162.4, 167.3. EI‐MS: (m/z) = 89 (M+), 269, 232, 221,
201, 176, 149, 110.
2.4.2 | 5(2‐Cl‐Benzylidene) barbituric acid
(4c)
FT‐IR (KBr, νmax, cm−1): 3460, 3120, 2981, 1754, 1569,
1
1454, 1079, 910, 782. HNMR (CDCl3, δ, ppm): 7.36 (t,
1H, H─ Ar), 7.47 (t, 1H, H─ Ar), 7.53 (d, 1H, H─ Ar),
7.73 (d, 1H, Ar─ H), 8.29 (s, 1H, HC═ C), 11.25 (s, 1H,
NH), 11.47 (s, 1H, NH). 13C NMR (CDCl3, δ, ppm):
121.76, 126.29, 128.29, 131.88, 132.25, 133.15, 146.70,
150.16, 160.85, 162.60. EI‐MS: m/z (%) 250 (M+).
3 | RESULTS AND DISCUSSION
2.4.3 | 5(4‐OH‐Benzylidene) barbituric
In recent years, the introduction of new catalysts for the
promotion of organic reactions has become an important
part of our ongoing research programme.[37–39] Based on
the above mentioned difficulties in the preparation of 5‐
arylidine barbituric acids and pyrano[2,3‐d] pyrimidine
derivatives and in continuation of our ongoing research
programme on the introduction of new nanocatalysts
for the promotion of organic reactions, we were inter-
ested in preparing, characterizing and studying the appli-
cability of Fe3O4@SiO2‐Sultone in the synthesis of these
compounds. After preparation of the reagent as described
in Section 2, it was characterized using various methods,
and the obtained results are summarized in the following
sections.
acid (4 h)
FT‐IR (KBr, νmax, cm−1): 3420, 3214, 2970, 1755, 1703,
1
1570. H NMR (DMSO, δ, ppm): 6.86 (d, 2H, Ar─ H),
8.32 (2d, 2H, Ar─ H), 8.24 (s, 1H, HC═ C), 10.68 (S, 1H,
OH), 11.13 (s, H, NH), 11.25 (S, 1H, NH). 13C NMR
(CDCl3, δ, ppm): 115.60, 118.76, 128.70, 148.80, 150.20,
157.65, 165.10. EI‐MS: m/z (%) 232 (M+).
2.4.4 | 7‐Amino‐5‐(4‐methoxyphenyl)‐2,4‐
dioxo‐1,3,4,5‐tetrahydro‐2H‐pyrano[2,3‐d]
pyrimidine‐6‐carbonitrile (5i)
FT‐IR (KBr, νmax, cm−1): 3317, 3282, 3145, 3063, 2215,
1743, 1668. 1H NMR (DMSO, δ, ppm): 10.98 (s, 1H,
NH), 10.80 (s, 1H, NH), 7.14 (d, J = 7.5 Hz, 2H, Ar═
H), 6.86–6.82 (m, 4H, Ar═ H and NH2), 4.16 (s, 1H,
CH), 3.81 (s, 3H, OCH3). 13C NMR (DMSO, δ, ppm):
161.99, 159.11, 155.61, 151.97, 151.36, 130.34, 129.50,
123.56, 113.14, 93.41, 58.66, 57.46, 53.46. MS (m/z) (%):
313.01 (M+).
3.1 | Characterization of Fe3O4@SiO2‐
Sultone
3.1.1 | FT‐IR analysis
FT‐IR spectra of Fe3O4, Fe3O4@SiO2 and Fe3O4@SiO2‐
Sultone are compared in Figure 1. These spectra showed

4 of 11
POURGHASEMI‐LATI ET AL.
(5 1 1) and (4 4 0) are readily recognized in the XRD pat-
tern. The observed diffraction peaks match with those of
the standard Fe3O4 sample (JCPDS file no. 19–0629). The
average crystallite size was calculated to be 10.7 nm using
the Scherrer equation.
3.1.3 | Thermal analysis
The thermal stability of Fe3O4@SiO2‐Sultone was deter-
mined using TGA (Figure 3). The weight loss of about
0.89% at a temperature below 130 °C can be related to
desorption of water molecules from the catalyst surface.
Also, another weight loss of 0.72% appears at around
240 °C due to decomposition of sulfuric acid and forma-
tion of sulfur dioxide. The complete loss of covalently
attached organic moiety was observed in the range
420–600 °C. The amount of organic moiety was found
to be about 12.12% against total solid catalyst.
FIGURE 1 FT‐IR spectra of (a) Fe3O4, (b) Fe3O4@SiO2 and (c)
Fe3O4@SiO2‐Sultone
3.1.4 | SEM analysis
broad bands at around 550–650 cm−1, which were attrib-
uted to Fe─
Samples of Fe3O4 and Fe3O4@SiO2‐Sultone were also
analysed using SEM for determining the size distribution,
particle shape and surface morphology, as illustrated in
Figure 4. The SEM images of Fe3O4 and Fe3O4@SiO2‐
Sultone samples show that Fe3O4 has an amorphous
morphology with particles of ca 10 nm in size and the syn-
thesized Fe3O4@SiO2‐Sultone has nanometric dimensions
ranging from ca 50 to 60 nm. It was also observed that all
the supported particles have highly porous surfaces suit-
able for harbouring and shielding catalytic species and
these particles are roughly globular in shape.
O
vibrations.[40] In the spectra of
Fe3O4@SiO2 and Fe3O4@SiO2‐Sultone, the strong bands
observed at 1078 and 1088 cm−1 can be due to the Si─
O─ Si stretching modes of the silica shell. The peak at
1154 cm−1 is related to the stretching of S═ O bonds.
The S─ O stretching modes of sulfunic acid functional
group lies at around 637 cm−1 proving the probable prep-
aration of the catalyst.
3.1.2 | Powder XRD analysis
Figure 2 shows the XRD pattern of Fe3O4@SiO2‐Sultone.
Diffraction peaks at 2θ= 30.4°, 35.8°, 43.3°, 54.0°, 57.6°
and 63.2° corresponding to (2 2 0), (3 1 1), (4 0 0), (4 2 2),
3.1.5 | Transmission electron microscopy
analysis
Also, a study of the same region of Fe3O4@SiO2‐Sultone
using transmission electron microscopy (TEM) confirmed
that the magnetite particles were evenly distributed
within this composite material (Figure 5). To our delight,
TEM analysis of Fe3O4@SiO2‐Sultone showed a well‐
dispersed pattern of nanoparticles in a narrow size range
of 50–60 nm.
3.1.6 | Energy‐dispersive X‐ray analysis
The energy‐dispersive X‐ray (EDX) spectrum of
Fe3O4@SiO2‐Sultone is shown in Figure 6. This clearly
shows the presence of Fe, N, O, C, Si and S in
Fe3O4@SiO2‐Sultone.
FIGURE 2 XRD pattern of Fe3O4@SiO2‐Sultone

POURGHASEMI‐LATI ET AL.
5 of 11
FIGURE 3 TGA curve of Fe3O4@SiO2‐Sultone
FIGURE 4 SEM images od (a) Fe3O4 and (b–d) Fe3O4@SiO2‐Sultone
FIGURE 5 TEM images Fe3O4@SiO2‐Sultone
structure, it is anticipated that this reagent may be able
to catalyse the reactions which need acidic catalysts to
increase their rate. In order to establish this suggestion,
the catalytic effect of this reagent in the synthesis of
3.2 | Application of Fe3O4@SiO2‐Sultone
The results obtained from the structural studies directed
us to accept that the prepared reagent can be formu-
lated as Fe3O4@SiO2‐Sultone. On the basis of this
5‐arylidine
barbituric
acids
and
pyrano[2,3‐d]

6 of 11
POURGHASEMI‐LATI ET AL.
obtained using 25 mg of Fe3O4@SiO2‐Sultone at room
temperature in water (Scheme 2).
After optimization of the reaction conditions, we
scrutinized the efficiency of Fe3O4@SiO2‐Sultone in the
preparation of 5‐arylidine barbituric acid derivatives
using various types of aldehydes containing
electron‐withdrawing as well as electron‐donating
groups. All the selected aldehydes gave the desired prod-
ucts in good to excellent yields during short reaction
times (Table 2).
The proposed mechanism for the synthesis of
5‐arylidine barbituric acid derivatives in the presence
of the prepared catalyst is shown in Scheme 3.
According to this mechanism and in the first step, the
aldehyde is activated by a proton from Fe3O4@SiO2‐
Sultone. Then, the carbonyl carbon is attacked by the
nucleophilic compound to produce the Knoevenagel
products.
FIGURE 6 EDX spectrum of Fe3O4@SiO2‐Sultone
pyrimidine derivatives, as two model reactions, was
studied.
First of all and in order to optimize the reaction con-
ditions and the amounts of the catalyst, the reaction
between 4‐chlorobenzaldehyde and barbituric acid was
studied in the presence of Fe3O4@SiO2‐Sultone. For
choosing the reaction media, various solvents such as
H2O, EtOH, CH2Cl2 and CH3CN and also solvent‐free
conditions were used and the best results were obtained
in aqueous media. Moreover, the effects of the amount
of the catalyst and temperature were examined in the
model reaction (Table 1). Finally the best result was
Recyclability is an important factor for judging the
sustainability of any catalyst. In this study, the recyclabil-
ity of the catalyst was examined in the synthesis of 5‐
arylidine barbituric acid derivative obtained from the
reaction of 4‐chlorobenzaldehyde with barbituric acid
under the optimized reaction conditions. When the reac-
tion was completed, the catalyst was easily recovered by
magnetic decantation. The recovered catalyst was washed
with ethanol and diethyl ether (Figure 7), dried and
reused over eight runs for the same reaction. Each time
TABLE 1 Optimization of reaction conditions for synthesis of 5‐arylidene barbituric acid derivative of 4‐chlorobenzaldehyde and
barbituric acid catalysed by Fe3O4@SiO2‐Sultonea
Entry
Catalyst (mg)
Solvent
Temp. (°C)
Time (min)
Conversion (%)
1
2
20
25
35
25
25
25
25
20
25
35
EtOH
EtOH
EtOH
—
r.t.
60
60
60
60
60
60
4
20
20
r.t.
3
r.t.
20
4
Reflux
r.t.
50
5
—
10
6
—
60
20
7
H2O
H2O
H2O
H2O
60
100
100
100
100
8
r.t.
8
9
r.t.
4
10
r.t.
4
aReaction conditions: 4‐chlorobenzaldehyde (1 mmol), barbituric acid (1 mmol) and Fe3O4@SiO2‐Sultone.
SCHEME 2 Synthesis of 5‐arylidine
barbituric acid derivatives catalysed by
Fe3O4@SiO2‐Sultone

POURGHASEMI‐LATI ET AL.
7 of 11
TABLE 2 Preparation of 5‐arylidine barbituric acid derivatives catalysed by Fe3O4@SiO2‐Sultonea
M.p. (°C)
Found
Time
(min)
Yield
(%)b
Entry
ArCHO
Product
Reported
1
C6H4CHO
4a
4b
4c
5
4
98
98
95
92
93
92
90
94
90
95
95
90
95
98
98
95
257–259
295–297
265–266
292–293
269–272
239–240
275–277
>300
255–256[17]
298–300[22]
268[41]
288–290[15]
268–270[15]
242–243[42]
274–276[17]
>300[42]
249–250[17]
266–268[43]
296–298[15]
275–277[17]
210–214[17]
>300[18]
2
4‐ClC6H4CHO
3
2‐ClC6H4CHO
5
4
4‐BrC6H4CHO
4d
4e
6
5
4‐NO2C6H4CHO
3‐NO2C6H4CHO
2‐NO2C6H4CHO
4‐OHC6H4CHO
2‐OHC6H4CHO
C6H5CH═ CHCHO
4‐MeOC6H4CHO
4‐CH3C6H4CHO
3‐CH3C6H4CHO
4‐CHOC6H4CHO
3‐CHOC6H4CHO
2‐Naphthaldehyde
5
6
4f
8
7
4 g
4 h
4i
8
8
10
12
7
9
246–248
267–269
295–297
276–277
208–209
>300
10
11
12
13
14
15
16
4j
4 k
4 l
4 m
4n
4o
4p
5
12
8
10
10
6
>300
>300[18]
263–264
266 (dec.)[44]
aReaction conditions: benzaldehyde (1 mmol), barbituric acid (1 mmol) and Fe3O4@SiO2‐Sultone (25 mg); in H2O at room temperature.
bIsolated yields.
SCHEME 3 Proposed mechanism for synthesis of 5‐arylidene barbituric acid using Fe3O4@SiO2‐Sultone
FIGURE 7 Separation of Fe3O4@SiO2‐
Sultone in water using an external
magnetic field

8 of 11
POURGHASEMI‐LATI ET AL.
the product was obtained with the least change in the
reaction time and yield (Figure 8).
5‐Arylidene barbituric acid derivatives have previ-
ously been synthesized using various methods, but these
methods either gave low yields or involved complex reac-
tion conditions (Table 3). It is clear that the present
method is superior in terms of reaction time and amount
of catalyst.
After the successful application of Fe3O4@SiO2‐
Sultone in the preparation of 5‐arylidene barbituric acid
derivatives from aldehydes and barbituric acid, we
decided to prepare pyrano[2,3‐d] pyrimidine derivatives
in the presence of this reagent. The optimization studies
FIGURE 8 Reusability of Fe3O4@SiO2‐Sultone in the reaction of
4‐chlorobenzaldehyde with barbituric acid
TABLE 3 Comparative performance of previously reported catalysts and Fe3O4@SiO2‐Sultone in the synthesis of 5‐(4‐chlorobenzylidene)
pyrimidine‐2,4,6(1H,3H,5H)trione
Entry Catalyst/conditions
Time (min) Yield(%)a TOF (h−1
)
Ref.
[21]
1
2
3
4
5
6
7
8
SiO2.12WO3.24H2O/H2O, r.t.
40
96
77.9
96
91
93
82
94
98
8000
10.82
77.5
[42]
[22]
[20]
[44]
[45]
[17]
1‐n‐Butyl‐3‐methylimidazolium tetrafluoroborate ([bmim]BF4)/grinding, r.t. 120
Aminosulfonic acid/grinding
CoFe2O4/water–ethanol/r.t.
180
2
15.16
6.88
PVP‐Ni nanoparticles/ethylene glycol, 50 °C
CTAMB/H2O, r.t.
5
30
5
91.11
15166
50
[DABCO](SO3H)2Cl2/H2O, 70 °C
Fe3O4@SiO2‐Sultone/H2O, r.t.
4
This work
aIsolated yields.
TABLE 4 Optimization of reaction conditions for synthesis of pyrano[2,3‐d] pyrimidine derivatives catalysed by Fe3O4@SiO2‐Sultonea
Entry
Catalyst (mg)
Solvent
Temp. (°C)
Time (min)
Conversion (%)
1
2
15
25
35
25
25
25
25
25
25
25
H2O
H2O
60
60
20
12
95
100
100
95
3
H2O
60
12
4
H2O
r.t.
60
40
5
EtOH
CH2Cl2
CH3CN
—
60
50
6
60
120
120
60
20
7
60
20
8
r.t.
100
60
20
9
—
60
40
10
H2O/EtOH
20
100
aReaction conditions: 4‐chlorobenzaldehyde (1 mmol), barbituric acid (1 mmol), malononitrile (1 mmol) and Fe3O4@SiO2‐Sultone.
SCHEME 4 Synthesis of pyrano[2,3‐d]
pyrimidine derivatives catalysed by
Fe3O4@SiO2‐Sultone

POURGHASEMI‐LATI ET AL.
9 of 11
(Table 4) showed that the suitable conditions for the syn-
thesis of pyrano[2,3‐d] pyrimidines in the presence of
Fe3O4@SiO2‐Sultone were as shown in Scheme 4.
After optimization of the reaction conditions, various
types of aromatic aldehydes were used in the same reac-
tion under the determined conditions and the results
TABLE 5 Preparation of pyrano[2,3‐d] pyrimidine derivatives catalysed by Fe3O4@SiO2‐Sultonea
M.p. (°C)
Found
Time
(min)
Yield
(%)b
Entry
ArCHO
R
Product
Reported
1
C6H4CHO
CN
5a
5b
5c
10
12
15
20
15
17
25
20
12
10
35
15
35
30
25
40
50
98
97
95
92
98
95
90
95
97
95
98
95
95
95
90
90
87
222–223
295–297
210–212
237–239
238–239
262–264
253–255
>300
224–225[17]
298–300[46]
213–215[17]
235–236[29]
236–237[17]
266–268[17]
254–256[17]
>300[46]
2
4‐ClC6H4CHO
2‐ClC6H4CHO
4‐BrC6H4CHO
4‐NO2C6H4CHO
3‐NO2C6H4CHO
2‐NO2C6H4CHO
4‐OHC6H4CHO
4‐MeOC6H4CHO
3‐MeOC6H4CHO
4‐CHOC6H4CHO
4‐CH3C6H4CHO
C6H4CHO
CN
3
CN
4
CN
5d
5e
5
CN
6
CN
5f
7
CN
5 g
5 h
5i
8
CN
9
CN
277–278
207–209
>320
280–284[29]
200–206[29]
>320[17]
10
11
12
13
14
15
16
17
CN
5j
CN
5 k
5 l
5 m
5n
5o
5p
5q
CN
221–223
207–210
>300
225[27]
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
206–210[47]
>300[48]
289–293[47]
297–298[48]
225[27]
4‐ClC6H4CHO
4‐NO2C6H4CHO
4‐MeOC6H4CHO
4‐MeC6H4CHO
295–297
293–295
220–222
aReaction conditions: benzaldehyde (1 mmol), barbituric acid (1 mmol), malononitrile (1 mmol) and Fe3O4@SiO2‐Sultone (25 mg); in H2O at 60 °C.
bIsolated yields.
SCHEME 5 Proposed mechanism for
synthesis of pyrano[2,3‐d] pyrimidine
derivatives using Fe3O4@SiO2‐Sultone

10 of 11
POURGHASEMI‐LATI ET AL.
TABLE 6 Comparison of performance of previously reported catalysts with that of Fe3O4@SiO2‐Sultone in synthesis of 7‐amino‐6‐cyano‐5‐
(4‐nitrophenyl)‐5H‐pyrano[2,3‐d]pyrimidine
Entry
Catalyst/conditions
Time (min)
Yield(%)a
TOF (h−1
)
Ref.
[35]
1
2
3
4
5
6
7
8
KAl (SO4)2.12H2O/H2O, 80 °C
45
92
72
92
95
73
80
83
98
0.34
0.1
[28]
[49]
[46]
[30]
[50]
[17]
Diammonium hydrogen phosphate/(H2O, EtOH), r.t.
DABCO/(H2O, EtOH), r.t.
120
120
720
45
0.13
—
Al‐HMS‐20/EtOH, r.t.
L‐Proline/(H2O, EtOH), r.t.
0.54
0.38
1106
13.3
Tetrabutylammonium bromide (TBAB)/H2O, reflux
[DABCO](SO3H)2Cl2/H2O, reflux
Fe3O4@SiO2‐Sultone/H2O, 60 °C
35
25
15
This work
aIsolated yields.
are summarized in Table 5. Using this method, all reac-
tions were performed under mild and completely hetero-
geneous reaction conditions with high yields and in short
reaction times.
in aqueous media. The procedure gave the products in
excellent yields in very short reaction times. The most
important advantages of the method include the simplic-
ity in the preparation procedure, easy work‐up, high reac-
tion rates, excellent yields, recyclability of the catalysts
using an external magnet and eco‐friendly procedure.
Further work to utilize this catalyst in other organic syn-
theses and transformations is in progress.
The proposed mechanism for the synthesis of
pyrano[2,3‐d] pyrimidine derivatives in the presence of
the catalyst is shown in Scheme 5. According to this
mechanism, the aldehyde is activated by a proton from
Fe3O4@SiO2‐Sultone. Then, the carbonyl carbon is
attacked by the nucleophilic compound to produce the
Knoevenagel products. In continuation, a Michael addi-
tion occurs. The Michael adduct tautomerizes in the pres-
ence of acidic catalyst to generate intermediate I. This
intermediate cyclizes to give the related intermediate II,
which tautomerizes to produce the fully aromatized
compound.
ACKNOWLEDGEMENTS
The authors are grateful to the Guilan and Zanjan Uni-
versities Research Councils for the partial support of this
work.
ORCID
To investigate the reusability of the catalyst, the reac-
tion of 4‐chlorobenzaldehyde, barbituric acid and
malononitrile under the optimized reaction conditions
was studied. After the separation of the catalyst using
an external magnet, the catalyst was washed with ethanol
and diethyl ether, dried and reused for the same reaction.
This process was carried out over seven runs and each
time the product was obtained in high yields during short
reaction times.
Table 6 presents a comparison of our results with
those reported using other catalysts in the synthesis of
pyrano[2,3‐d] pyrimidine derivatives. This comparison
indicates that in most cases, the reaction time is too long
in the presence of the other nanocatalysts.
F. Shirini http://orcid.org/0000-0002-0768-3241
REFERENCES
[1] F. Kabiri Esfahani, D. Zareyee, R. Yousefi, ChemCatChem
2014, 6, 3333.
[2] F. Nemati, M. M. Heravi, R. Saeedi Rad, Chin. J. Catal. 2012,
33, 1825.
[3] M. Haghighat, F. Shirini, M. Golshekan, J. Mol. Struc. 2018,
1171, 168.
[4] A. R. Karimi, Z. Eekhari, M. Karimi, Z. Dalirnasab, Synthesis
2014, 46, 3180.
[5] H. Naeimi, S. Mohamadabadi, Dalton Trans. 2014, 43, 12967.
[6] L. Ghandi, M. K. Miraki, I. Radfar, E. Yazdani, A. Heydari,
ChemistrySelect 2018, 3, 1787.
4 | CONCLUSIONS
[7] M. A. El Aleem, A. A. El‐Remaily, H. A. Hamad, J. Mol. Catal.
A 2015, 148, 404.
We have introduced a novel and heterogeneous catalyst
formulated as Fe3O4@SiO2‐Sultone as a highly powerful
nanomagnetic catalyst for the synthesis of 5‐arylidine
barbituric acids and pyrano[2,3‐d] pyrimidine derivatives
[8] H. Veisi, P. Mohammadi, J. Gholami, Appl. Organometal.
Chem. 2014, 28, 868.
[9] R. Ghorbani‐Vaghei, N. Sarmast, Appl. Organometal. Chem.
2018, 32, e4003.

POURGHASEMI‐LATI ET AL.
11 of 11
[10] H. Veisi, S. Taherib, S. Hemmati, Green Chem. 2016, 18, 6337.
[34] M. M. Heravi, A. Ghods, F. Derikvand, K. Bakhtiari, F. F.
Bamoharram, J. Iran. Chem. Soc. 2010, 7, 615.
[11] S. Mirfakhraei, M. Hekmati, F. Hosseini Eshbalab, H. Veisi,
New J. Chem. 2018, 42, 1757.
[35] A. Mobinikhaledi, N. Foroughifar, M. A. B. Fard, Synth. React.
Inorg. Met.‐Org. Nano‐Met. Chem 2010, 40, 179.
[12] F. Bonyasi, M. Hekmati, H. Veisi, J. Colloid Interface Sci. 2017,
496, 177.
[36] Z. Cheng, Z. Gao, W. Maa, Q. Sun, B. Wang, X. Wang, Chem.
Eng. J. 2012, 209, 451.
[13] J. Mondal, A. Biswas, S. Chiba, Y. Zhao, Sci. Rep. 2015, 5, 8294.
[14] A. Bamoniri, N. Moshtael‐Arani, RSC Adv. 2015, 5, 16911.
[37] F. Shirini, M. Abedini, M. Seddighi, J. Nanosci. Nanotechnol.
2016, 16, 8208.
[15] N. R. Dighore, P. L. Anandgaonker, S. T. Gaikwad, A. S.
[38] F. Shirini, M. Abedini, S. Zarrabzadeh, M. Seddighi, J. Iran.
Chem. Soc. 2015, 12, 2105.
Rajbhoj, Res. J. Chem. Sci. 2014, 4, 93.
[16] K. M. Khan, M. Ali, T. A. Farooqui, M. Khan, M. Tahan, S.
[39] F. Shirini, M. Pourghasemi Lati, J. Iran. Chem. Soc. 2017, 14,
Perveen, J. Chem. Soc. Pak. 2009, 31, 823.
75.
[17] N. Seyyedi, F. Shirini, M. S. N. Langarudi, RSC Adv. 2016, 6,
[40] S. Sobhani, M. S. Ghasemzadeh, M. Honarmand, Catal. Lett.
2014, 144, 1515.
44630.
[18] S. B. Rathod, A. B. Ghamhire, B. R. Arbad, M. K. Lande, Bull.
Korean Chem. Soc. 2010, 31, 339.
[41] S. Kamble, G. Rashinkar, A. Kumbhar, K. Mote, R. Salunkhe,
Arch. Appl. Sci. Res. 2010, 2, 217.
[19] M. T. Maghsoodlou, N. Hazeri, S. M. Habibi‐Khorassani, Z.
Shahkarami, N. Maleki, M. Rostamizadeh, M. Moradian, Iran.
J. Org. Chem. 2010, 2, 391.
[42] C. Wang, J. J. Ma, X. Zhou, X. H. Zang, Z. Wang, Y. J. Gao, P.
L. Cui, Synth. Commun. 2005, 35, 2759.
[43] J. K. Rajput, J. Kaur, Chin. J. Catal. 2013, 34, 1697.
[44] J. M. Khurana, K. Vij, Catal. Lett. 2010, 138, 104.
[20] J. R. Kaur, G. Kaur, Chin. J. Catal. 2013, 34, 1697.
[21] J. T. Li, M. X. Sun, Aust. J. Chem. 2009, 62, 353.
[45] Z. Ren, W. Cao, W. Tong, X. Jing, Synth. Commun. 2002, 32,
[22] J. T. Li, H. G. Dai, D. Liu, T. S. Li, Synth. Commun. 2006,
36, 789.
1947.
[46] B. Sabour, M. H. Peyrovi, M. Hajimohammadi, Res. Chem.
Intermed. 2015, 41, 1343.
[23] E. A. Maadi, C. L. Matthiesen, P. Ershadi, J. Baker, D. M.
Herron, E. M. Holt, J. Chem. Crystallogr. 2003, 33, 757.
[47] A. R. Bhata, A. H. Shallab, R. S. Dongrea, JTUSCI 2016, 10, 9.
[24] G. L. Anderson, J. L. Shim, A. D. Broom, J. Org. Chem. 1976,
41, 1095.
[48] H. R. Safaei, M. Shekouhy, S. Rahmanpur, A. Shirinfeshan,
Green Chem. 2012, 14, 1696.
[25] D. Heber, C. Heers, U. Ravens, Pharmazie 1993, 48, 537.
[49] J. Azizian, A. Shameli, S. Balalaie, M. M. Ghanbari, S.
Zomorodbakhsh, M. Entezari, S. Bagheri, G. Fakhrpour, Ori-
ent. J. Chem. 2012, 28, 327.
[26] Y. Sakuma, M. Hasegawa, K. Kataoka, K. Hoshina, N. Kadota,
Chem. Abstr. 1991, 115, 71646.
[27] M. M. Heravi, A. Ghods, K. Bakhtiari, F. Derikvand, Synth.
Commun. 2010, 40, 1927.
[50] A. Mobinikhaledi, M. A. Bodaghi‐Fard, Acta Chim. Slov. 2010,
57, 931.
[28] S. Balalaie, S. Abdolmohammadi, H. R. Bijanzadeh, A. M.
Amani, Mol. Diversity 2008, 12, 85.
[29] G. M. Ziarani, S. Faramarzi, S. Asadi, A. Badiei, R. Bazl, M.
How to cite this article: Pourghasemi‐Lati M,
Shirini F, Alinia‐Asli M, Rezvani MA. Butane‐1‐
sulfonic acid immobilized on magnetic
Amanlou, DARU J. Pharm. Sci. 2013, 21, 3.
[30] M. Bararjanian, S. Balalaie, B. Movassagh, A. M. Amani,
J. Iran. Chem. Soc. 2009, 6, 436.
Fe3O4@SiO2 nanoparticles: A novel and
[31] J. Yu, H. Wang, Synth. Commun. 2005, 35, 3133.
heterogeneous catalyst for the one‐pot synthesis of
barbituric acid and pyrano[2,3‐d] pyrimidine
derivatives in aqueous media. Appl Organometal
Chem. 2018;e4455. https://doi.org/10.1002/aoc.4455
[32] A. A. Shestopalov, L. A. Rodinovskaya, A. M. Shestopalov, V. P.
Litvinov, Russ. Chem. Bull. 2004, 53, 724.
[33] H. H. Zoorob, M. Abdelhamid, M. A. El‐Zahab, M. Abdel‐
Mogib, Arzneim. Forsch. 1997, 47, 958.