4-(4-Propylpiperazine-1-yl)butane-1-sulfonic acid-modified silica-coated magnetic nanoparticles: A novel and recyclable catalyst for the synthesis of 5-arylidinebarbituric acids and pyrano[2,3-d]pyrimidinedione derivatives in aqueous media

Article abstract of DOI:10.1002/aoc.4605

A mild, simple and efficient procedure for the preparation of barbituric acid and pyrano[2,3-d]pyrimidine derivatives in aqueous media is described using 4-(4-propylpiperazine-1-yl)butane-1-sulfonic acid-modified silica-coated magnetic nanoparticles as a novel and reusable catalyst. The catalyst was easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused at least eight times without significant degradation in activity.

Full text of DOI:10.1002/aoc.4605

Received: 23 June 2018
DOI: 10.1002/aoc.4605
Revised: 18 August 2018
Accepted: 28 August 2018
F U L L P A P E R
4‐(4‐Propylpiperazine‐1‐yl)butane‐1‐sulfonic acid‐modified
silica‐coated magnetic nanoparticles: A novel and recyclable
catalyst for the synthesis of 5‐arylidinebarbituric acids and
pyrano[2,3‐d]pyrimidinedione derivatives in aqueous media
M. Pourghasemi‐Lati1 | F. Shirini2
| M. Alinia‐Asli1 | M.A. Rezvani1
1 Department of Chemistry, College of
A mild, simple and efficient procedure for the preparation of barbituric acid
Science, University of Zanjan, Zanjan
45195‐313, Iran
and pyrano[2,3‐d]pyrimidine derivatives in aqueous media is described using
2 Department of Chemistry, College of
Science, University of Guilan, Rasht
41335, Iran
4‐(4‐propylpiperazine‐1‐yl)butane‐1‐sulfonic
acid‐modified
silica‐coated
magnetic nanoparticles as a novel and reusable catalyst. The catalyst was easily
isolated from the reaction mixture by magnetic decantation using an external
magnet and reused at least eight times without significant degradation in
activity.
Correspondence
Farhad Shirini, Department of Chemistry,
College of Science, University of Guilan,
Rasht, 41335, Iran.
KEYWORDS
Email: fshirini@gmail.com
aqueous media, barbituric acid, heterogeneous catalyst, magnetite nanoparticles, pyrano[2,3‐d]
M. Alinia‐Asli, Department of Chemistry,
College of Science, University of Zanjan,
Zanjan, 45195‐313, Iran.
pyrimidines
Email: m_aliniaaslir@znu.ac.ir
1 | INTRODUCTION
methods are effective, most of them suffer from draw-
backs such as harsh reaction conditions, use of harmful
5‐Arylidinebarbituric
acids
and
pyrano[2,3‐d]
organic solvents, long reaction times, tedious work‐up
procedures, expensive and moisture‐sensitive reagents,
strongly acidic conditions, unsatisfactory yields, non‐
recoverability of the catalyst and environmental pollu-
tion. Hence, finding newer and more efficient methods
for the synthesis of these types of compounds is still
important.
Reactions in aqueous media have many advantages
such as high polarity that causes immiscibility with most
organic compounds, simple work‐up and environmental
friendliness. Also, reactions in aqueous media are
cheaper to operate and particularly important in industry.
Magnetic nanoparticles (MNPs) play a basic role in
modern sciences and technologies due to their wide range
of applications in various fields such as magnetic reso-
nance imaging,[27] hyperthermia,[28] fluid transport,[29]
drug delivery,[30] environmental remediation[31] and het-
erogeneous catalysis.[32]
pyrimidinedione derivatives are important classes of het-
erocyclic compounds which have attracted great interest
due to their widespread biological and pharmacological
properties, such as antitumour,[1] cardiotonic,[2]
antibronchitic,[3] antimalarial,[4] antihypertensive,[5]
analgesic[6] and antiviral[7] properties. A variety of cata-
lysts and reagents have been used to facilitate the synthe-
sis of 5‐arylidinebarbituric acids including CuO‐NPs,[8]
BiCl3,[9]
[DABCO](SO3H)2Cl2,[10]
Ce1MgxZr1−xO2
(CMZO),[11] BF3/nano‐g‐Al2O3,[12] CoFe2O4,[13] SiO2⋅
12WO3⋅24H2O,[14] NH2SO3H[15] and K2NiP2O7.[16]
Pyrano[2,3‐d]pyrimidinedione derivatives have also been
prepared in the presence of various catalysts, such as
Zn[L‐proline]2,[17] DAHP,[18] SBA‐Pr‐SO3H,[19] L‐pro-
line,[20] [BMIm]BF4,[21] N‐methylmorpholine,[22] 1,4‐
dioxane,[23]
H14[NaP5W30O110],[24]
dibutylamine
(DBA)[25] and [KAl (SO4)2].[26] Although some of these
Appl Organometal Chem. 2018;e4605.
wileyonlinelibrary.com/journal/aoc
© 2018 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4605

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POURGHASEMI‐LATI ET AL.
Fe3O4 MNPs have superparamagnetic properties.
2.2 | Catalyst Preparation
2.2.1 | Preparation of 4‐(4‐
These magnetic nanomaterials have gained significant
popularity as heterogeneous supports for various catalytic
species due to their easy preparation, good stability, ease
of surface modification, high dispersibility, low toxicity,
high surface area and easy recovery from solution using
an external magnet.
In order to limit the aggregation of Fe3O4 nanopar-
ticles, their surface is usually modified with silica layer,
because the surface of silanol groups can easily
react with various organic and inorganic materials to
achieve specific purposes particularly in the field of
catalysis.[33]
The use of recyclable solid acids in organic reactions
is often considered for pursuing the principles of green
chemistry. Nanostructured solid acids exhibit high activ-
ity and selectivity. Also, MNPs are unique due to their
thermal stability, easy recovery by magnetic separation
and higher catalytic activity.[34] Thus the combination of
the advantageous of homogeneous protic acids and solid
properties using silica‐coated Fe3O4 nanoparticles is a
useful and attractive way to prepare efficient catalytic
systems.
propylpiperazine‐1‐yl)butane‐1‐sulfonic
acid‐modified silica‐coated MNPs
(Fe3O4@SiO2‐Propyl‐pip‐SO3H.HSO4)[35]
Magnetite (Fe3O4) nanoparticles of approximately 9–
11 nm in size were synthesized using a reported chemical
co‐precipitation technique.[36] The thus prepared Fe3O4
MNPs (4 g) were dispersed in a mixture of deionized
water (48 ml) and ethanol (180 ml) by ultrasonication
for 30 min. Subsequently, NH3⋅H2O (4.0 ml, 25%) and
tetraethyl orthosilicate (TEOS; 2.4 ml) were charged to
the reaction dish. After stirring at room temperature for
12 h, the silica‐coated nanoparticles (Fe3O4@SiO2) 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.
Then the obtained brown precipitate (3.0 g) in dry tol-
uene (40 ml) was sonicated for 30 min. After this time, 3‐
chloropropyltrimethoxysilane (1.0 ml) was added to the
dispersed Fe3O4@SiO2 in toluene and slowly heated to
105°C. The reaction mixture was stirred at this tempera-
ture for 24 h. The residue was separated using an external
magnet and washed three times with diethyl ether and
dichloromethane and dried at 40°C in vacuum for 24 h.
After this step, piperazine (2.83 g) was added to a magnet-
ically stirred mixture of the prepared Fe3O4@SiO2‐Propyl‐
Cl (2.78 g) in dry toluene (40 ml), and the mixture was
stirred at room temperature for 36 h. The resulting solid
material was separated using an external magnet, washed
with diethyl ether and dichloromethane, and dried at
40°C in vacuum to afford Fe3O4@SiO2‐Propyl‐Pip MNPs.
In continuation, the sulfonation of the obtained
MNPs was executed using the reaction of Fe3O4@SiO2‐
Propyl‐Pip MNPs with 1,4‐butanesultone. For this pur-
pose, Fe3O4@SiO2‐Propyl‐Pip MNPs (0.5 g) and 1,4‐
butanesultone (1.2 ml) were suspended in dry toluene
(40 ml) and the colloidal solution was refluxed for 48 h,
followed by introduction with one equivalent of H2SO4
(0.62 ml) to yield the magnetically retrievable reagent
(Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4) and the separation
was repeated as in previous steps (Scheme 1).
2 | EXPERIMENTAL
2.1 | Chemicals
All chemicals, including iron(II) chloride tetrahydrate
(99%), iron(III) chloride hexahydrate (98%) and alde-
hyde 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 Fourier transform infrared (FT‐IR),
1H NMR and 13C NMR spectroscopies. Purity determi-
nation of substrates and reaction monitoring were
accomplished by TLC using 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‐Nanotechnol-
ogy Company, Japan). Samples were heated from 25 to
700°C at 10°C min−1 under nitrogen atmosphere. Scan-
ning election microscopy (SEM) images were obtained
with a Philips XL30. Wide‐angle X‐ray diffraction
(XRD) measurements were performed at room tempera-
2.3 | Catalytic Activity
2.3.1 | General procedure for preparation
of 5‐arylidinebarbituric acids
ture with
a Siemens D‐500 X‐ray diffractometer
(Germany), using Ni‐filtered Co Kα radiation
(λ = 0.15418 nm). The chemical composition was
obtained using energy‐dispersive X‐ray (EDX) analysis
(ESEM, Philips XL30).
Aromatic aldehyde (1.0 mmol), barbituric acid (1.0 mmol)
and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 (25 mg) in
water (10 ml) were stirred at 60°C for the appropriate
time. After evaporation of the solvent, the product was

POURGHASEMI‐LATI ET AL.
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SCHEME 1 Synthesis of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4
dissolved in warm ethanol. The catalyst was then sepa-
rated using an external magnet from the aqueous ethanol.
The obtained products were characterized using FT‐IR,
1H NMR and 13C NMR spectroscopies and by comparison
of their melting points with reported ones.
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 (2C). EI‐MS: m/z 250 (M+).
2.4.3 | 5‐(4‐Hydroxybenzylidene)
barbituric acid
2.3.2 | General procedure for preparation
of pyrano[2,3‐d]pyrimidinedione
derivatives
FT‐IR (KBr, νmax, cm−1): 3420, 3216, 2970, 1755, 1703,
1
1570. H NMR (DMSO, δ, ppm): 6.86 (d, 2H, Ar—H),
8.31 (dd, 2H, Ar—H), 8.24 (s, 1H, HC═C), 10.68 (s, 1H,
OH), 11.13 (s, 1H, NH), 11.25 (s, 1H, NH). 13C NMR
(CDCl3, δ, ppm): 115.60 (2C), 118.76, 128.70, 148.80
(2C), 150.20, 152.32, 157.65, 165.10 (2C). EI‐MS: m/z 232
(M+).
A mixture of the aromatic aldehyde (1.0 mmol),
barbituric acid (1.0 mmol), ethyl cyanoacetate (1.0 mmol)
and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 (30 mg) in
water (10 ml) was stirred at 80°C for the appropriate time.
After completion of the reaction, the catalyst was col-
lected using an external magnet and the product was
purified by recrystallization from aqueous ethanol. The
obtained products were characterized using FT‐IR, 1H
NMR and 13C NMR spectroscopies and by comparison
of their melting points with reported ones.
2.4.4 | 7‐Amino‐5‐(4‐methoxyphenyl)‐2,4‐
dioxo‐1,3,4,5‐tetrahydro‐2H‐pyrano[2,3‐d]
pyrimidine‐6‐carbonitrile
FT‐IR (KBr, νmax, cm−1): 3319, 3282, 3145, 3063, 2215,
1743, 1668. 1H NMR (DMSO, δ, ppm): 3.81 (s, 3H,
OCH3), 4.16 (s, 1H, CH), 6.80–6.89 (m, 4H, Ar—H and
NH2), 7.14 (d, J = 7.5 Hz, 2H, Ar—H), 10.80 (s, 1H,
NH), 10.98 (s, 1H, NH). 13C NMR (DMSO, δ, ppm):
53.46, 57.46, 58.66, 93.41, 113.14, 123.56, 129.50, 130.34,
151.36, 151.97, 155.61, 159.11, 161.99. MS: m/z 313.01
(M+).
2.4 | Spectroscopic data
2.4.1 | 5‐(4‐Chlorobenzylidene)barbituric
acid
FT‐IR (KBr, νmax, cm−1): 3404, 3213, 2970, 1755, 1703,
1
1570. H NMR (DMSO, δ, ppm): 7.53 (d, 2H, Ar—H),
8.08 (dd, 2H, Ar—H), 8.25 (s, 1H, HC═C), 11.25 (s, 1H,
NH), 11.40 (s, 1H, NH). 13C NMR (CDCl3, δ, ppm):
117.46, 127.70, 128.29 (2C), 133.25, 133.50 (2C), 148.70,
150.16, 165.10 (2C). EI‐MS: m/z 250 (M+).
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
FT‐IR (KBr, νmax, cm−1): 3311, 3188, 3091, 2228, 1690,
1648, 1543. H NMR (400 MHz, DMSO, δ, ppm): 1.17 (t,
J = 7.1 Hz, 3H, CH3), 3.8 (s, 1H, CH), 4.11 (q,
J = 7.0 Hz, 2H, CH2), 7.28 (m, 2H, 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): 27.09, 39.5,
2.4.2 | 5‐(2‐Chlorobenzylidene)barbituric
1
acid
FT‐IR (KBr, νmax, cm−1): 3462, 3121, 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),

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POURGHASEMI‐LATI ET AL.
67.1, 78.3, 83.3, 128.8 (2C), 129.9 (2C), 130.5, 139.2, 150.1,
155.4, 155.8, 159.7, 160.9. MS: (M+) m/z 313, 278, 188,
153, 111, 77, 57, 43.
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
FT‐IR (KBr, νmax, cm−1): 3413, 3278, 2239, 2165, 1695,
1
1662, 1543. H NMR (400 MHz, DMSO, δ, ppm): 1.29 (t,
J = 7.2 Hz, 3H, CH3), 3.32 (s, 3H, OCH3), 3.71 (s, 1H,
CH), 4.41 (q, J = 7.1 Hz, 2H, CH2), 6.93 (m, 2H, H
—Ar), 7.65 (m, 2H, H—Ar), 7.09 (s, 2H, NH2), 10.03 (s,
1H, NH), 11.09 (s, 1H, NH), 13C NMR (CDCl3, δ, ppm):
23.03, 37.2, 55.8, 62.02, 75.6, 78.9, 114.2, 130.1, 134.1,
143.9, 150.5, 157.2, 162.4, 165.2, 167.3. EI‐MS: m/z = 89
(M+), 269, 232, 221, 201, 176, 149, 110.
3 | RESULTS AND DISCUSSION
FIGURE
1
FT‐IR spectra of Fe3O4 (a), Fe3O4@SiO2 (b),
Fe3O4@SiO2‐Propyl‐Pip (c) and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.
HSO4 (d)
In recent years, the introduction of new catalysts for the
promotion of organic reactions has become an important
part of our ongoing research programme.[35,37–44] Herein
and in continuation of these studies, we report the use
of our novel magnetic Fe3O4‐based nanoreagent formu-
lated as Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4[35] as a cata-
lyst in the preparation of 5‐arylidinebarbituric acids and
pyrano[2,3‐d]pyrimidinedione derivatives.
3.1.2 | Powder XRD
The XRD pattern of Fe3O4 clearly matches with the liter-
ature data from JCPDS 79‐0419. Notably, the same peaks
were also observed in the XRD pattern of Fe3O4@SiO2‐
Propyl‐Pip‐SO3H.HSO4, with slight changes in the nature
of the peaks, which could be due to the presence of sul-
fonic acid functionality on the surface of the prepared
reagent (Fig. 2).
3.1 | Catalyst Characterization
3.1.1 | FT‐IR analysis
FT‐IR spectra of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2‐Pro-
pyl‐Pip and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 are com-
pared in Fig. 1. These spectra show broad bands at
around 550–650 cm−1, which are attributed to Fe—O
vibrations. In the spectra of Fe3O4@SiO2, Fe3O4@SiO2‐
Propyl‐Pip and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4, the
strong band observed at around 1000–1200 cm−1 can be
due to Si—O—Si stretching modes of the silica shell. In
the case of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4, the
strong bands at 1150 and 1432 cm−1 are related to the
stretching modes of the S═O bonds and the broad band
around 1100 cm−1 is assigned to other stretching modes
of S═O which is overlapped with the stretching modes
of Si—O. In this spectrum the bands corresponding to
S—O stretching modes of sulfonic acid functional group
lie at around 804 and 875 cm−1. This comparison con-
firms the probable preparation of the catalyst.
FIGURE 2 XRD pattern of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4

POURGHASEMI‐LATI ET AL.
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3.1.3 | Thermal analysis
3.1.5 | EDX analysis
The thermal stability of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.
HSO4 was investigated using TGA (Fig. 3). The loss of
the adsorbed water on the support and silane groups
resulted in initial weight loss of 0.87% up to 120°C.
Another peak appears in the range from 120 to 200°C
due to decomposition of the sulfonic acid group and for-
mation of sulfur dioxide. According to TGA, the amount
of sulfonic acid functionality on Fe3O4 is evaluated to be
0.18%. The curve also shows a steady weight loss in the
range from 200 to 600°C, which could be ascribed to the
loss of covalently attached organic moiety. The amount
of organic moiety was found to be about 8.68% against
total solid catalyst.
The EDX spectrum of the Fe3O4@SiO2‐Propyl‐Pip‐SO3H.
HSO4 sample is shown in Fig. 5 Which clearly show the
presence of N, C and S elements in the Fe3O4@SiO2‐Pro-
pyl‐Pip‐SO3H.HSO4 catalyst. Moreover, the presence of
Si, O and Fe signals indicates the wrapping of SiO2 on
the Fe3O4 particles, and the considerable intensity of the
Si peak indicates that the Fe3O4 nanoparticles were
trapped by SiO2. According to the above analysis, it can
be concluded that Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4
had been successfully synthesized.
3.2 | Application of Fe3O4@SiO2‐Propyl‐
pip‐SO3H.HSO4
After successful use of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.
HSO4 in the synthesis of 1‐(benzothiazolylamino)
phenylmethyl‐2‐naphthols, we were interested in investi-
gating the applicability of this reagent in the promotion of
the synthesis of 5‐arylidinebarbituric acids and
pyrano[2,3‐d]pyrimidinedione derivatives in aqueous
media.
3.1.4 | SEM analysis
The samples of Fe3O4 and nano‐sized Fe3O4@SiO2‐Pro-
pyl‐Pip‐SO3H.HSO4 were analysed using SEM for deter-
mination of particle shape, surface morphology and size
distribution (Fig. 4). The SEM images of Fe3O4 and
Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 samples show that
these particles are roughly spherical in shape, and the
average size is about 10–15 and 65–75 nm, respectively.
An increase of the average size of Fe3O4@SiO2‐Propyl‐
Pip‐SO3H.HSO4 is in agreement with its preparation.
At first and in order to optimize the reaction condi-
tions, the reaction of 4‐chlorobenzaldehyde and
FIGURE 5 EDX spectrum of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.
FIGURE 3 TGA curve of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4
HSO4
FIGURE 4 SEM micrographs of Fe3O4 (1 μm) (a), Fe3O4@SiO2‐Propyl‐Pip‐SO3H (1 μm) (b) and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4
(500 nm) (c)

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POURGHASEMI‐LATI ET AL.
TABLE 1 Optimization of reaction conditions for synthesis of 5‐arylidinebarbituric acid derivatives using Fe3O4@SiO2‐Propyl‐Pip‐SO3H.
a
HSO4
Entry
Catalyst (mg)
Solvent
Temp. (°C)
Time (min)
Conversion (%)
1
2
25
25
25
15
35
25
25
25
25
25
H2O
r.t.
60
80
60
60
60
60
60
60
60
60
10
10
30
5
100
100
100
80
H2O
3
H2O
4
H2O
5
H2O
100
100
50
6
H2O–EtOH
EtOH
—
40
90
90
90
90
7
8
20
9
CH2Cl2
CH3CN
20
10
20
aReaction conditions: 4‐chlorobenzaldehyde (1 mmol), barbituric acid (1 mmol) and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 under various conditions.
SCHEME 2 Synthesis of 5‐
arylidinebarbituric acid derivatives
catalysed by Fe3O4@SiO2‐Propyl‐Pip‐
SO3H.HSO4
a
TABLE 2 Preparation of 5‐arylidinebarbituric acid derivatives catalysed by Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4
M.p. (°C)
Time
(min)
Yield
(%)b
Entry
Aldehyde
Found
Reported
1
C6H4CHO
12
10
15
10
15
20
25
12
12
20
22
20
20
25
30
40
45
89
95
89
88
93
88
88
92
94
95
89
90
85
85
92
91
90
248–250
298–300
261–263
290–292
273–274
229–232
273–275
>300
255–256[10]
298.5[45]
2
4‐ClC6H4CHO
3
2‐ClC6H4CHO
268[15]
4
4‐BrC6H4CHO
292–293[45]
268–270[46]
231–233[13]
274–276[10]
>300[45]
249–250[13]
306–308[47]
268–269[8]
210–214[8]
268[45]
5
4‐NO2C6H4CHO
3‐NO2C6H4CHO
2‐NO2C6H4CHO
4‐OHC6H4CHO
2‐OHC6H4CHO
4‐MeOC6H4CHO
2‐MeOC6H4CHO
3‐CH3C6H4CHO
C6H5CH&dbond;CHCHO
4‐NMe2C6H4CHO
2‐Naphthaldehyde
4‐CHOC6H4CHO
3‐CHOC6H4CHO
6
7
8
9
252–254
297–300
265–267
213–215
270–273
280–281
266 (dec.)
>300
10
11
12
13
14
15
16
17
281–282[47]
266 (dec.)[45]
>300[10]
>300
>300[10]
aReaction conditions: aldehyde (1 mmol), barbituric acid (1 mmol) and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 (25 mg) in H2O at 60°C.
bIsolated yields.

POURGHASEMI‐LATI ET AL.
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barbituric acid was selected as a model reaction and the
effects of various conditions including amount of catalyst
and temperature were explored (Table 1). For choosing
the reaction media, various solvents such as EtOH,
H2O, CH2Cl2 and CH3CN and also solvent‐free conditions
were used for this reaction. The best result was obtained
using 25 mg of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 when
the reaction is proceeded in water at 60°C (Scheme 2). It
is important to note that using smaller amounts of the
catalyst led to the product in longer times.
After optimization of the reaction conditions and in
order to establish the effectiveness and the applicability
of the method, the protocol was explored for a variety of
FIGURE 6 Reusability of fe3o4@sio2‐propyl‐pip‐so3h.hso4 in
the reaction of 4‐chlorobenzaldehyde with barbituric acid
TABLE 3 Comparison of performance of various catalysts and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 in synthesis of 5‐(4‐chlorobenzylidene)
pyrimidine‐2,4,6‐(1H,3H,5H)‐trione (Table 2, entry 2)
Entry
Catalyst/conditions
Time (min)
Yield (%)a
Ref.
[45]
1
2
3
4
5
6
7
8
1‐n‐Butyl‐3‐methylimmidazoliumtetrafluoroborate ([bmim]BF4)/grinding
Aminosulfonic acid/grinding
120
180
5
77
96
93
92
94
91
98
95
[15]
[47]
[48]
[11]
[13]
[8]
PVP‐Ni nanoparticles/ethylene glycol, 50°C
NaPTSA/solvent free, r.t.
4
CMZO/solvent free, microwave
3
CoFe2O4 nanoparticles/water–ethanol, r.t.
Copper oxide nanoparticles/solvent‐free, r.t.
Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4/H2O, 60°C
2
12
10
This work
aIsolated yields.
TABLE 4 Optimization of reaction conditions for synthesis of pyrano[2,3‐d]pyrimidine derivatives using Fe3O4@SiO2‐Propyl‐Pip‐SO3H.
a
HSO4
Entry
Catalyst (mg)
Solvent
Temp. (°C)
Time (min)
Conversion (%)
1
2
3
4
5
6
7
8
20
30
40
30
30
30
30
30
H2O
80
80
20
20
15
10
60
60
60
60
80
100
100
100
80
H2O
H2O
80
H2O
Reflux
80
H2O–EtOH
H2O
r.t.
20
EtOH
EtOH
r.t.
20
80
20
aReaction conditions: 4‐chlorobenzaldehyde (1 mmol), barbituric acid (1 mmol), malononitrile (1 mmol) and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 under various
conditions.
SCHEME 3 Synthesis of pyrano[2,3‐d]
pyrimidinone derivatives catalysed by
Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4

8 of 11
POURGHASEMI‐LATI ET AL.
a
TABLE 5 Preparation of pyrano[2,3‐d]pyrimidine derivatives catalysed by Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4
M.p. (°C)
Found
Time
(min)
Yield
(%)b
Entry
Aldehyde
X
Reported
1
C6H4CHO
CN
15
20
25
15
20
15
30
30
25
50
60
60
70
90
90
90
95
92
90
97
90
90
87
90
85
90
85
80
95
85
219–220
240–242
210–212
227–230
240–243
265–268
268–270
>300
221–224[49]
246[50]
2
4‐ClC6H4CHO
2‐ClC6H4CHO
4‐BrC6H4CHO
4‐NO2C6H4CHO
3‐NO2C6H4CHO
4‐MeOC6H4CHO
4‐OHC6H4CHO
4‐CHOC6H4CHO
C6H4CHO
CN
3
CN
211–212[51]
230–231[18]
238–240[25]
267–269[42]
266–270[10]
>300[49]
4
CN
5
CN
6
CN
7
CN
8
CN
9
CN
>300
>300[52]
10
11
12
13
14
15
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
202–204
>300
206–210[25]
>300[53]
4‐ClC6H4CHO
4‐NO2C6H4CHO
3‐NO2C6H4CHO
4‐MeOC6H4CHO
4‐MeC6H4CHO
286–289
245–248
293–295
230–233
289–293[25]
265[17]
297–298[53]
225[17]
aReaction conditions: 4‐chlorobenzaldehyde (1 mmol), barbituric acid (1 mmol), malononitrile (1 mmol) and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 (30 mg) in
H2O at 80°C.
bIsolated yields.
SCHEME 4 Proposed mechanism of studied reactions in the presence of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4

POURGHASEMI‐LATI ET AL.
9 of 11
Table 3 compares our results with the results reported
using various other catalysts in the synthesis of 5‐(4‐
chlorobenzylidene)pyrimidine‐2,4,6‐(1H,3H,5H)‐trione
(Table 2, entry 2). This comparison demonstrates the
favourable catalytic activity of Fe3O4@SiO2‐Propyl‐Pip‐
SO3H.HSO4 compared to the other catalysts presented in
Table 3.
After the successful application of Fe3O4@SiO2‐Pro-
pyl‐Pip‐SO3H.HSO4 in the preparation of 5‐
arylidinebarbituric acid derivatives, we attempted to
study the applicability of this catalyst in the promotion
of the synthesis of pyrano[2,3‐d]pyrimidinone derivatives
by studying the reaction of 4‐chlorobenzaldehyde,
barbituric acid and malononitrile in the presence of this
reagent. The obtained results (Table 4) indicated the suit-
able conditions for the synthesis of pyrano[2,3‐d]
pyrimidinones in the presence of Fe3O4@SiO2‐Propyl‐
Pip‐SO3H.HSO4, as shown in Scheme 3. After optimiza-
tion studies and to determine the efficiency of
Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 in the preparation
of pyrano[2,3‐d]pyrimidine derivatives, various aromatic
aldehydes were subjected to the same reaction under
the optimal conditions. The obtained results showed that
these conversions occurred with excellent yields in very
short times (Table 5).
FIGURE 7 Reusability of Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 in
the reaction of 4‐chlorobenzaldehyde, barbituric acid and
malononitrile
simple readily available substrates under the optimal con-
ditions. It was observed that under the optimized condi-
tions, a wide range of aromatic aldehydes containing
electron‐withdrawing as well as electron‐donating groups
such as Cl, Br, CH3, OCH3, Et, NO2 and OH in the ortho,
meta and para positions of the benzaldehyde ring in reac-
tion with barbituric acid were easily converted to the cor-
responding products in short reaction times with high
isolated yields (Table 2).
The recyclability of the catalyst was examined in the
synthesis of 5‐arylidinebarbituric acid derivatives. When
the reaction was completed, the catalyst was separated
using an external magnet, washed with ethanol and
diethyl ether, dried and reused for the same reaction. This
process was carried out over eight runs and each time the
product was obtained with the least change in the reac-
tion time and yield. The results are shown in Fig. 6.
The proposed mechanism for the synthesis of 5‐
arylidinebarbituric acids and pyrano[2,3‐d]pyrimidinone
derivatives in the presence of the catalyst is shown in
Scheme 4. According to this mechanism, the aldehyde is
activated by the proton from Fe3O4@SiO2‐Propyl‐Pip‐
SO3H.HSO4. Then, the activated aldehyde (1) is attacked
by activated barbituric acid (2) through a Knoevenagel
reaction to generate intermediate (I) and, with loss of a
TABLE 6 Comparison of performance of various catalysts and Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4 in the synthesis of pyrano[2,3‐d]
pyrimidine derivatives
Entry
Catalyst/conditions
Time (min)
Yield (%)a
Ref.
[17]
[25]
[24]
[18]
[26]
[19]
[49]
[21]
[23]
[50]
[54]
1
Zn[L‐proline]2/EtOH, reflux
30–720
43–129
30–60
120
80–92
83–94
85–90
71–81
80–90
30–90
84–95
82–95
60–70
73–91
59–92
90–98
2
DBA/(H2O, EtOH), reflux
3
H14[NaP5W30O110]/EtOH, reflux
DAHP/EtOH, r.t.
4
5
[KAl(SO4)2]/H2O, 80°C
40–50
5–45
6
SBA‐Pr‐SO3H/solvent‐free, 140°C
Al‐HMS‐20/EtOH, r.t.
7
720
8
[BMIm]BF4/90°C
180–300
1–2
9
1,4‐Dioxane/H2O, reflux
10
11
12
Fe3O4@SiO2@formamidinesulfinic acid/H2O, 80°C
Fe3O4@MCM‐41@Zr‐piperazine‐MNPs/(H2O, EtOH), 80°C
Fe3O4@SiO2‐Propyl‐Pip‐SO3H.HSO4/H2O, 80°C
360
6–35
15–90
This work
aIsolated yields.

10 of 11
POURGHASEMI‐LATI ET AL.
molecule of water, 5‐arylidinebarbituric acid derivatives
(a) are achieved (Table 2, entries 1–17).
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How to cite this article: Pourghasemi‐Lati M,
Shirini F, Alinia‐Asli M, Rezvani MA. 4‐(4‐
Propylpiperazine‐1‐yl)butane‐1‐sulfonic acid‐
modified silica‐coated magnetic nanoparticles: A
novel and recyclable catalyst for the synthesis of 5‐
arylidinebarbituric acids and pyrano[2,3‐d]
pyrimidinedione derivatives in aqueous media.
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