SCMNPs@Urea/Py-CuCl2: a recyclable catalyst for the synthesis of pyrano[2,3-d]pyrimidinone and pyrano[2,3-d] pyrimidine-2,4,7-trione derivatives

Article abstract of DOI:10.1080/00958972.2020.1737681

An efficient, simple, and mild strategy for the one-pot multicomponent synthesis of pyrano[2,3-d]pyrimidinone and pyrano[2,3-d]pyrimidine-2,4,7-trione derivatives is described using SCMNPs@Urea/Py-CuCl₂ nanoparticles as a reusable heterogeneous magnetic nanocatalyst. The catalyst was characterized using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The SCMNPs@Urea/Py-CuCl₂ can be easily collected from the reaction solution by magnetic decantation using a permanent magnetic field and reused in six runs without significant decrease in catalytic activity.

Full text of DOI:10.1080/00958972.2020.1737681

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: https://www.tandfonline.com/loi/gcoo20
SCMNPs@Urea/Py-CuCl2: a recyclable catalyst for
the synthesis of pyrano[2,3-d]pyrimidinone and
pyrano[2,3-d] pyrimidine-2,4,7-trione derivatives
Jun Zhang, Hongqing Song, Ruirui Cui, Chaoyong Deng & Qahtan A. Yousif
To cite this article: Jun Zhang, Hongqing Song, Ruirui Cui, Chaoyong Deng & Qahtan
A. Yousif (2020): SCMNPs@Urea/Py-CuCl2: a recyclable catalyst for the synthesis of
pyrano[2,3-d]pyrimidinone and pyrano[2,3-d] pyrimidine-2,4,7-trione derivatives, Journal of
Coordination Chemistry, DOI: 10.1080/00958972.2020.1737681
To link to this article: https://doi.org/10.1080/00958972.2020.1737681
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JOURNAL OF COORDINATION CHEMISTRY
https://doi.org/10.1080/00958972.2020.1737681
SCMNPs@Urea/Py-CuCl2: a recyclable catalyst for the
synthesis of pyrano[2,3-d]pyrimidinone and pyrano[2,3-d]
pyrimidine-2,4,7-trione derivatives
Jun Zhanga,b,c, Hongqing Songa,c, Ruirui Cuia,c, Chaoyong Denga,c and
Qahtan A. Yousifd
aCollege of Big Data and Information Engineering, Guizhou University, Guiyang, Guizhou, China;
bCollege of Computer and Information Engineering, Guizhou University of Commerce, Guiyang,
c
Guizhou, China; Key Laboratory of Functional Composite Materials of Guizhou Province, Guizhou
d
University, Guiyang, Guizhou, China; College of Education, Department of Chemistry, University of
Al-Qadisiyah, Al Diwaniyah, Republic of Iraq
ABSTRACT
ARTICLE HISTORY
Received 10 December 2019
Accepted 10 February 2020
An efficient, simple, and mild strategy for the one-pot multicompo-
nent synthesis of pyrano[2,3-d]pyrimidinone and pyrano[2,3-d]pyr-
imidine-2,4,7-trione derivatives is described using SCMNPs@Urea/
Py-CuCl2 nanoparticles as a reusable heterogeneous magnetic
nanocatalyst. The catalyst was characterized using Fourier transform
infrared spectroscopy (FTIR), thermogravimetric analysis (TGA),
vibrating sample magnetometry (VSM), energy dispersive X-ray
spectroscopy (EDX), X-ray diffraction (XRD), and scanning electron
microscopy (SEM). The SCMNPs@Urea/Py-CuCl2 can be easily col-
lected from the reaction solution by magnetic decantation using a
permanent magnetic field and reused in six runs without significant
decrease in catalytic activity.
KEYWORDS
SCMNPs@Urea/Py-CuCl2;
pyrano[2,3-d]pyrimidinone;
pyrano[2,3-d]pyrimidine-
2,4,7-trione; multicompo-
nent synthesis; magnetic
nanocatalyst
CONTACT Chaoyong Deng
chaoyongdeng@163.com
ß 2020 Informa UK Limited, trading as Taylor & Francis Group

2
J. ZHANG ET AL.
1. Introduction
Synthesis of separable and reusable heterogeneous catalysts has received significant
attention [1–6]. One strategy to achieve this purpose is the functionalization of the het-
erogeneous supports with homogeneous catalysts [7]. To avoid tedious work-up proc-
esses like centrifugation and filtration, the catalysts can be supported on magnetic
nanoparticles as the core magnetic support and separated from the reaction media at the
end of the process via an external magnetic field due to the magnetic nature of these par-
ticles. After separating, rinsing, and drying of the catalysts, they can be reused several
times while keeping their primary activity. Fe3O4 magnetic nanoparticles (MNPs) have
been widely investigated among the various utilized nanoparticles because of their
technological applications [8, 9]. Naked Fe3O4 MNPs due to high initial chemical activity,
great surface area to volume ratio, and dipole-dipole attractions between MNPs tend to
oxidize and accumulate and they are susceptible to loss of their magnetic nature during
the reaction period [10]. Formation of an organic (polymers, surfactants) or inorganic (sil-
ica, carbon, calcium hydroxyapatite) shell on the MNPs was introduced to overcome their
drawback, which enhanced their chemical stability [11–19].
The use of barbituric acid as a 1,3-dicarbonyl compound in the synthesis of func-
tionalized pyrimidine compounds has attracted attention because they are very
important in natural material chemistry and pharmacological activities [20–22].
Synthesized derivatives of barbituric acid with alkyls and aryls have hypnotic and
seductive properties while the precursor itself does not exhibit these properties [23,
24]. The pyrano fused pyrimidines like pyrimido[2,3-d]pyrimidinone have been investi-
gated due to its wide-range of pharmaceutical and biological properties such as anti-
hypertensive, antimicrobial, antitumor, antifungal, anti-inflammatory, antiallergic,
antibacterial, and antimalarial [25–31]. Some of these heterocyclic compounds can be
utilized in photoactive materials, cosmetics, and pigments [32, 33]. The pyrano[2,3-
d]pyrimidine-2,4,7-triones are among other pyrano fused pyrimidines. These biologic-
ally active compounds with pyrimidinone scaffolds have attracted much attention
because of their potent antitumor function in the treatment of P388 leukemia and
B16 melanoma [34–36]. Also, pyrano[2,3-d]pyrimidine-2,4,7-triones are diverse and
densely functionalized heterocyclic molecules that show antiplatelet antimicrobial,
anticonvulsant, as well as antifungal activities [37–41].
2. Experimental
All the pure substances were purchased from Fluka, Merck, and Aldrich Chemical
€
Companies. Melting points of the substrate were determined using a Buchi B-545 appar-
atus in open capillary tubes. FT-IR spectroscopy was performed using a Perkin Elmer spec-
trum BX series. TGA spectra were obtained using a Linseis SATPT 1000 thermoanalyzer.
Magnetic susceptibility measurements were examined using a vibrating sample magnet-
ometry (VSM; Lake Shore 7200 at 300 K VSM). The chemical composition was done by
energy dispersive X-ray spectroscopy (EDX) on ESEM, Philips, and XL30. ICP analysis was
carried out on a VISTA-PRO, CCD simultaneous ICP analyzer. Powder X-ray diffraction
(XRD) was carried out on a Siemens D-500 X-ray diffractometer (Munich, Germany).
Scanning electron microscopy was done with a SEM-LEO 1430VP analyzer.

JOURNAL OF COORDINATION CHEMISTRY
3
2.1. Fe3O4 nano-particles preparation
To prepare Fe3O4 nanoparticles, a mixture of FeCl3ꢀ6H2O (6.68 g) and FeCl2ꢀ4H2O
(2.55 g) was poured in 150 mL deionized water and stirred mechanically under N2.
Then, 22 mL of NH4OH (25 wt%) was injected into the reaction solution until pH ¼ 11.
The reaction solution was stirred at 70 ꢁC for 1 h. The resulting mixture was cooled to
25 ꢁC and the magnetic nanoparticles were isolated by a permanent magnetic field,
rinsed three times with deionized water, and dried under vacuum.
2.2. Synthesis of silica-coated magnetic nanoparticles (Fe3O4@SiO2)
0.1 g of prepared Fe3O4 MNPs was dispersed in a solution mixture of 150 mL ethanol,
10 mL deionized water and 7 mL NH4OH (25%) under mechanical stirring for 25 min.
Then, 0.3 mL of tetraethylorthosilicate (TEOS) was added dropwise to the reaction solu-
tion under vigorous sonication for another 25 min. After continuous stirring for 7 h,
the silica-coated magnetic nanoparticles were collected by magnetic decantation and
then rinsed several times with water and ethanol to remove unreacted chemicals;
finally, they were dried under vacuum.
2.3. Preparation of Fe3O4@SiO2/PC nanoparticles
Two grams of prepared Fe3O4@SiO2 nanoparticles were suspended in 50 mL of dry
toluene and sonicated for 30 min in an ultrasonic bath. Then, 4 mL of 3-chloropropyl-
triethoxysilane (PC) was added into the reaction vessel and the reaction mixture was
refluxed for 24 h under nitrogen gas. Next, the resulting solid product was isolated
using a permanent magnetic field and rinsed three times with water and ethanol to
remove any unreacted chemicals; finally, it was dried under vacuum.
2.4. Preparation of SCMNPs@urea
1 g of core-shell Fe3O4@SiO2/PC nanoparticles and 1.2 g of KI were poured in 75 mL
acetonitrile and dispersed using ultrasonication for 30 min. Next, 0.5 g of urea and
1.1 g of K2CO3 were added into the reaction solution and refluxed for 24 h under nitro-
gen. After this period, the resultant solid precipitates were collected from the solution
by an external magnet and then washed several times with water/ethanol. Finally, the
solid product was dried in a vacuum oven.
2.5. Preparation of SCMNPs@urea/Py
1 g of SCMNPs@Urea was dispersed in 50 mL dry ethanol under ultrasonic irradiation
for 30 min. After that, 2.5 mmol of pyridine-2-carbaldehyde (Py) was added to the reac-
tion vessel, and the mixture was stirred for 24 h under reflux conditions. Finally, the
resultant solid product was isolated using an external magnet and washed thoroughly
with ethanol and dried in an oven at 60 ꢁC for 12 h.

4
J. ZHANG ET AL.
Scheme 1. The SCMNPs@Urea/Py-CuCl2 synthesis.
2.6. Preparation of SCMNPs@urea/Py-CuCl2
1 g of the SCMNPs@Urea/Py was dispersed in 75 mL of ethanol under ultrasonic irradi-
ation for 30 min and 0.3 g of CuCl2 was added to the reaction mixture. Afterwards, the
solution was refluxed for 12 h and the solid product was collected by magnetic
decantation in the presence of the external magnet, washed thoroughly with ethanol,
and dried in an oven. All stages of the SCMNPs@Urea/Py-CuCl2 preparation are illus-
trated in Scheme 1.
2.7. General process for synthesis of pyrano[2,3-d]pyrimidinone derivatives (4)
A mixture of barbituric acid (1 mmol), aldehyde (1 mmol), malononitrile (1.1 mmol),
and SCMNPs@Urea/Py-CuCl2 (12 mg) was refluxed in the presence of H2O-EtOH as a
suitable solvent for the appropriate time. The reaction was monitored by TLC [n-hexa-
ne:ethyl acetate (7:4 ratio)] analyses. At the end of the reaction, the reaction solution
was cooled to room temperature and then the catalyst was removed using an external
magnetic field. The remaining mixture was isolated by filtration and the achieved
product was purified by re-crystallization in aqueous EtOH (25%).
2.8. General process for synthesis of pyrano[2,3-d]pyrimidine-2,4,7-trione
derivatives (6)
A mixture of barbituric acid (1 mmol), aldehyde (1 mmol), Meldrum’s acid (1 mmol),
and SCMNPs@Urea/Py-CuCl2 (15 mg) was refluxed in the presence of H2O as a green
and suitable solvent for the appropriate time. The reaction was monitored by TLC [n-
hexane:ethyl acetate (9:5 ratio)] analyses. At the end of the reaction, the reaction solu-
tion was cooled to room temperature and then the catalyst was removed using an

JOURNAL OF COORDINATION CHEMISTRY
5
Figure 1. FTIR spectra of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2/PC, SCMNPs@Urea, SCMNPs@Urea/Py,
and SCMNPs@Urea/Py-CuCl2.
external magnetic field. The remaining mixture was isolated by filtration and the
achieved product was purified by re-crystallization in aqueous EtOH (25%).
3. Results and discussion
3.1. FTIR analysis of SCMNPs@Urea/Py-CuCl2
FT-IR spectra of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2/PC, SCMNPs@Urea, SCMNPs@Urea/Py,
and SCMNPs@Urea/Py-CuCl2 samples from 400 to 4000 cmꢂ1 are shown in Figure 1.
The bands at 586 cmꢂ1 and 3379 cmꢂ1 in Fe3O4 can be attributed to the stretching
vibration of the Fe-O and O-H of the water molecule. In the FT-IR spectrum of the
Fe3O4@SiO2, the absorption peaks at 975 and 1045 cmꢂ1 are related to the Si-O-Si and
Si-OH stretches, respectively. The band at 2975 cmꢂ1 of Fe3O4@SiO2/PC is attributed to
the C-H stretch after treating the Fe3O4@SiO2 with 3-chloropropyltriethoxysilane. The
FT-IR spectrum of SCMNPs@Urea illustrates the peak at 1631 cmꢂ1 that is indexed to
the C ¼ O bond of the amide group. In the FTIR spectrum of SCMNPs@Urea/Py, the
characteristic bands between 1400 and 1600 cmꢂ1 and the absorption at 1638 cmꢂ1
can be, respectively, ascribed to the C ¼ C and C ¼ N groups. The appearance of the
same bands in the FT-IR spectrum of SCMNPs@Urea/Py-CuCl2 is also confirmed.
3.2. Thermal analysis of SCMNPs@Urea/Py-CuCl2
The thermal stability of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2/PC, SCMNPs@Urea,
SCMNPs@Urea/Py, and SCMNPs@Urea/Py-CuCl2 were also studied by thermogravimetric

6
J. ZHANG ET AL.
Figure 2. TGA graphs of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2/PC, SCMNPs@Urea, SCMNPs@Urea/Py,
and SCMNPs@Urea/Py-CuCl2.
analyzer under nitrogen at 10 ꢁC.minꢂ1 of heating rate (Figure 2). TGA data for all samples
have slight weight loss below 235 ꢁC due to evaporation of the physically adsorbed water
molecules and dehydration of silica layers. Another weight loss at 430 ꢁC was found in
TGA curves of Fe3O4@SiO2/PC and SCMNPs@Urea, which can be related to decompos-
ition of attached 3-chloropropyltriethoxysilane and urea groups on the Fe3O4@SiO2 sur-
face. SCMNPs@Urea/Py and SCMNPs@Urea/Py-CuCl2 have weight loss stages at 370 and
580 ꢁC, respectively, which are associated with the decomposition of functionalized
groups grafted to the Fe3O4 surface.
3.3. VSM analysis of SCMNPs@Urea/Py-CuCl2
Magnetic features of Fe3O4, Fe3O4@SiO2, and SCMNPs@Urea/Py-CuCl2 were determined
using a vibrating sample magnetometer (VSM) at ambient temperature (Figure 3). The
saturation magnetization (Ms) of Fe3O4 and Fe3O4@SiO2 were 62.56 and 50.86 emu
g
ꢂ1, respectively, which can be related to the functionalization of the Fe3O4 with the
silica layers. As shown, the value of the SCMNPs@Urea/Py-CuCl2 saturation magnetiza-
tion was 33.52 emu gꢂ1. This reduction in the value of Ms indicates formation of func-
tional groups on the surface of the Fe3O4@SiO2. The catalyst, even with this reduction
in the value of Ms, can be separated from the reaction solution using an external mag-
netic field.

JOURNAL OF COORDINATION CHEMISTRY
7
Figure 3. VSM patterns of Fe3O4, Fe3O4@SiO2, and SCMNPs@Urea/Py-CuCl2.
3.4. EDX analysis of SCMNPs@Urea/Py-CuCl2
The energy dispersive X-ray (EDX) spectrum was applied to identify the elemental
composition of the SCMNPs@Urea/Py-CuCl2, approving the presence of all expected
elements such as Fe, Si, Cu, C, N, and O (Figure 4). In addition, the ICP analysis demon-
strated that 4.5% (0.7 mmol per gram) of copper was anchored on SCMNPs@Urea/
Py-CuCl2.
3.5. XRD analysis of SCMNPs@Urea/Py-CuCl2
The XRD-diffraction patterns of Fe3O4 and SCMNPs@Urea/Py-CuCl2 confirm the crystal-
line nature of these nanoparticles (Figure 5). The XRD patterns of Fe3O4 show several
characteristic peaks at 2h ¼ 32.24ꢁ (220), 36.45ꢁ (311), 43.15ꢁ (400), 52.76ꢁ (422), 57.65ꢁ
(511) and 62.84ꢁ (440), corresponding to the crystalline cubic spinel structure and they
are in agreement with (JCPDS card no. 19-0629). The similar characteristic peaks were
also observed for SCMNPs@Urea/Py-CuCl2, indicating the stability of pure magnetic
nanoparticles by surface modification with imine and a coordination complex.
3.6. SEM analysis of SCMNPs@Urea/Py-CuCl2
The morphology and size of Fe3O4 and SCMNPs@Urea/Py-CuCl2 were evaluated using
scanning electron microscopy (SEM) as shown in Figure 6. The SEM images show that
porous surface and spherical nanoparticles were achieved with an average diameter
of 38–45 nm.

8
J. ZHANG ET AL.
Figure 4. EDX spectrum of SCMNPs@Urea/Py-CuCl2.
Figure 5. XRD patterns of Fe3O4 and SCMNPs@Urea/Py-CuCl2.

JOURNAL OF COORDINATION CHEMISTRY
9
Figure 6. SEM image of Fe3O4 and SCMNPs@Urea/Py-CuCl2.
Scheme 2. Synthesis of pyrano[2,3-d]pyrimidinone and pyrano[2,3-d]pyrimidine-2,4,7-trione deriva-
tives using SCMNPs@Urea/Py-CuCl2.
Table 1. Optimization of the three-component reaction of barbituric acid (1), 4-chlorobenzalde-
hyde (2i), and malononitrile (3) under various amounts of the catalyst, temperature, and solventa.
Entry
Catalyst (mg)
Solvent
Temp. (ꢁC)
Time (min)/Yield (%)
1
2
3
4
5
6
7
8
12
12
12
12
12
12
12
12
12
6
H2O
EtOH
H2O-EtOH (1:1)
H2O-EtOH (2:1)
H2O-EtOH (1:2)
CH3CN
CH2Cl2
CHCl3
–
H2O-EtOH (1:1)
H2O-EtOH (1:1)
H2O-EtOH (1:1)
H2O-EtOH (1:1)
H2O-EtOH (1:1)
H2O-EtOH (1:1)
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
25 ꢁC
25/91
20/93
12/96
12/87
12/94
120/45
120/trace
120/trace
25/87
12/58
12/69
9
10
11
12
13
14
15
8
10
14
16
12
12/83
12/95
12/95
60/75
aReaction conditions: barbituric acid (1 mmol), 4-chlorobenzaldehyde (1 mmol), malononitrile (1.1 mmol), and
SCMNPs@Urea/Py-CuCl2 under various conditions.

10
J. ZHANG ET AL.
Table 2. Preparation of pyrano[2,3-d]pyrimidinone derivatives catalyzed by SCMNPs@urea/
a
Py-CuCl2 .
Entry Product
Aldehyde (2)
Compounds
Time (min.) Yield(%)b M.P (Obsd.) (ꢁC) M.P (Lit.) (ꢁC)
1
4a
20
91
210–212
215–217 [42]
2
4b
20
92
251–254
254–256 [43]
3
4c
15
96
225–228
230–231 [44]
4
5
4d
4e
15
20
93
91
251–253
269–271
254–255 [43]
267–269 [45]
6
4f
15
95
234–237
238–240 [46]
7
8
4g
4h
10
20
95
93
209–211
238–240
212–214 [47]
240–241 [47]
(continued)

JOURNAL OF COORDINATION CHEMISTRY
11
Table 2. Continued.
Entry Product
Aldehyde (2)
Compounds
Time (min.) Yield(%)b M.P (Obsd.) (ꢁC) M.P (Lit.) (ꢁC)
9
4i
12
96
237–239
242–243 [42]
233–235 [48]
10
4j
12
94
231–234
11
12
13
4k
4l
15
25
15
92
91
96
265–268
295–298
248–251
268–270 [46]
>300 [43]
4m
254–256 [48]
14
15
4n
4o
20
25
90
88
238–240
237–239
233–235 [43]
234–236 [43]
16
4p
18
92
272–274
266–270 [49]
(continued)

12
J. ZHANG ET AL.
Table 2. Continued.
Entry Product
Aldehyde (2)
Compounds
Time (min.) Yield(%)b M.P (Obsd.) (ꢁC) M.P (Lit.) (ꢁC)
17
4q
15
91
229–231
228–230 [50]
18
19
20
4r
4s
4t
15
20
20
87
90
89
222–224
239–241
230–232
224–225 [42]
242–246 [49]
234–235 [49]
21
22
23
4u
4v
15
18
15
92
90
94
237–239
235–236 [44]
>300
>300 [42]
4w
256–258
236(dec.) [44]
aReaction conditions: barbituric acid (1 mmol), aldehyde (1 mmol), malononitrile (1.1 mmol), and 12 mg of the
SCMNPs@Urea/Py-CuCl2.
bThe yields refer to the isolated product.
In this study, we investigate the effect of this recyclable magnetic catalyst on the
synthesis of pyrano[2,3-d]pyrimidinone and pyrano[2,3-d]pyrimidine-2,4,7-trione deriva-
tives (Scheme 2).
To optimize the conditions of the reaction for preparation of the 7-amino-5-(4-
chlorophenyl)ꢂ2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile,

JOURNAL OF COORDINATION CHEMISTRY
13
Table 3. Optimization of the three-component reaction of barbituric acid (1), 4-chlorobenzalde-
hyde (2h), and meldrum’s acid (5), under various amounts of the catalyst, temperature,
and solventa.
Entry
Catalyst (mg)
Solvent
Temp. (ꢁC)
Time (min)/Yield (%)
1
2
3
4
5
6
7
8
15
15
15
15
15
15
15
15
15
8
10
12
17
20
12
H2O
EtOH
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
25 oC
30/95
40/85
30/91
120/42
60/74
120/62
120/60
120/56
30/89
50/62
45/69
36/87
30/94
30/92
55/73
H2O-EtOH (1:1)
Toluene
CH3OH
CH3CN
CH2Cl2
CHCl3
–
H2O
H2O
H2O
H2O
9
10
11
12
13
14
15
H2O
H2O
aReaction conditions: barbituric acid (1 mmol), 4-chlorobenzaldehyde (1 mmol), Meldrum’s acid (1 mmol), and
SCMNPs@Urea/Py-CuCl2 under various conditions.
we commenced the study by treating a mixture of barbituric acid 1, 4-chlorobenzalde-
hyde 2i, and malononitrile 3 under various temperatures, solvents, and amounts of
the catalyst (Table 1). To corroborate the interference of solvents during this reaction,
we performed the model reaction in the presence of H2O, EtOH, H2O-EtOH, CH3CN,
CH2Cl2, CHCl3, and solvent-free conditions (Table 1, entries 1–9). The best result of the
reaction was achieved in the presence of H2O-EtOH as a suitable solvent after 12 min
of starting the reaction (Table 1, entry 3). To continue optimization of the reaction
conditions, we tested the effect of catalyst concentration by carrying out the model
reaction at concentrations ranging from 6 to 16 mg (Table 1, entries 3 and 10–14). As
shown, 12 mg was the optimum concentration of the catalyst in terms of product yield
and reaction time (Table 1, entry 3). Performing the model reaction in concentrations
above or below 12 mg did not produce the desired results compared to the optimized
value (Table 1, entries 10–14). Note that carrying out the reaction at room temperature
led to formation of the target product 4i in moderate yield and long reaction time
(Table 1, entry 15).
With a set of optimized reaction conditions at hand, we generalized the scope of
this transformation process for the preparation of pyrano[2,3-d]pyrimidinone deriva-
tives. Various aryl aldehydes with both electron-withdrawing and electron-donating
substituents were efficiently reacted with malononitrile and barbituric acid/(thio) barbi-
turic acid, which produced high-to-excellent yields of target products (4a-w) in less
reaction times. The results are summarized in Table 2.
For the optimization of the desired organic transformation conditions, the reaction
of barbituric acid 1, 4-cholorobenzaldehyde 2 h, and Meldrum’s acid 5 is selected as a
model reaction under various temperatures, solvents and amounts of the catalyst
(Table 3). Initially, the model reaction was performed in the presence of various sol-
vents such as H2O, EtOH, H2O-EtOH, toluene, CH3OH, CH3CN, CH2Cl2, CHCl3 and solv-
ent-free conditions (Table 3, entries 1–9). When the desired reaction was used in H2O
as the solvent, the time and yield of the reaction became shorter and higher, respect-
ively (Table 3, entry 1). After the selection of H2O as the best solvent, various amounts

14
J. ZHANG ET AL.
Table 4. Preparation of pyrano[2,3-d]pyrimidine-2,4,7-trione derivatives catalyzed by
a
SCMNPs@urea/Py-CuCl2 .
Time
(min.)
M.P (Obsd.)
(oC)
M.P (Lit/)
(oC)
Entry
1
Product
Aldehyde (2)
Product
Yield(%)b
94
6a
45
245–248
254–256 [51]
2
2
6b
6b
40
93
95
265–268
273–275 [51]
40
270–272
264–266 [52]
3
4
6c
35
40
95
92
218–221
270–272
216–218 [52]
6d
273 [53]
5
6e
35
94
243–246
250–252 [52]
6
7
6f
30
40
94
91
240–242
262–264
242–244 [52]
268–270 [51]
6g
(continued)

JOURNAL OF COORDINATION CHEMISTRY
15
Table 4. Continued.
Time
(min.)
M.P (Obsd.)
(oC)
M.P (Lit/)
Entry
8
Product
Aldehyde (2)
Product
Yield(%)b
95
(oC)
6h
30
287–299
284–286 [52]
9
6i
6j
45
45
90
92
293–295
297–299
290–292 [52]
>300 [51]
10
11
12
6k
6l
40
40
93
92
282–284
232–234
291–293 [51]
235–237 [53]
13
14
15
6m
6n
6o
45
35
35
93
95
94
271–274
291–294
281–233
277 [53]
290–291 [51]
280–282 [51]
(continued)

16
J. ZHANG ET AL.
Table 4. Continued.
Time
(min.)
M.P (Obsd.)
(oC)
M.P (Lit/)
(oC)
Entry
16
Product
Aldehyde (2)
Product
Yield(%)b
92
6p
35
263–265
268–270 [51]
17
18
6q
6r
30
40
93
90
265–268
289–291
260–261 [51]
280–282 [51]
aReaction conditions: barbituric acid (1 mmol), aldehyde (1 mmol), Meldrum’s acid (1 mmol), and 15 mg of the
SCMNPs@Urea/Py-CuCl2.
bThe yields refer to the isolated product.
of the catalyst ranging from 8 to 20 mg were selected to generate the requested prod-
ucts (Table 3, entries 1 and 10–14). When the reaction was performed with 15 mg of
the catalyst, the reaction produced the highest yield of the product with less reaction
time (Table 3, entry 1). Carrying out the reaction in high or low concentrations of the
catalyst relative to the optimized value did not lead to highest yields of the product
(Table 3, entries 10–14). At room temperature, when the reaction was done in H2O,
moderate percentage of the desired product was obtained in longer reaction time
(Table 3, entry 15).
According to the best optimal condition achieved, several pyrano[2,3-d]pyrimidine-
2,4,7-trione derivatives were prepared and the outcomes are listed in Table 4. To study
the catalyst efficiency to determine the scope of the present system, various pyrimi-
dines (6a–r) were synthesized by the one-pot condensation reaction of a barbituric
acid, wide range of aromatic aldehydes with both electron-withdrawing and electron-
donating substituents, and Meldrum’s acid at high-to-excellent yields and in shorter
reaction times. The results are shown in Table 4.
A probable mechanism for the synthesis of pyrano[2,3-d]pyrimidinone and pyr-
ano[2,3-d]pyrimidine-2,4,7-trione derivatives catalyzed by SCMNPs@Urea/Py-CuCl2 is
presented in Scheme 3. The first step may be initiated with the Knoevenagel conden-
sation of malononitrile 3/Meldrum’s acid 5 to activated carbonyl group of aldehyde 2
by the catalyst, resulting in intermediates 7 and 8. These intermediates may further
tolerate Michael addition with barbituric acid 1 and generate polar transition states 9
and 10. These unstable intermediates undergo an intramolecular cyclization, dehydra-
tion and aromatization to afford desired products 4 and 6.

JOURNAL OF COORDINATION CHEMISTRY
17
Scheme 3. A plausible mechanism for the one-pot, three-component reaction of barbituric acid 1,
aldehyde 2, and malononitrile 3/Meldrum’s acid 5 catalyzed by SCMNPs@Urea/Py-CuCl2.
Recyclability of the synthesized catalyst was investigated for preparation of 7-amino-5-
(4-chlorophenyl)ꢂ2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile
4i (a) and 5-(4-chlorophenyl)ꢂ5,6-dihydro-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-tri-
one 6h (b) in the presence of SCMNPs@Urea/Py-CuCl2. Upon completion of the reaction,

18
J. ZHANG ET AL.
Figure 7. The recycling of SCMNPs@Urea/Py-CuCl2 in the synthesis of 7-amino-5-(4-chlorophenyl)-
2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile 4i (a) and 5-(4-chlorophenyl)-
5,6-dihydro-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-trione 6h (b).
Table 5. Comparison of the results of the production of products 4i (entries 1–5) and 6h
(entries 6–10).
Cl
Cl
O
O
CN
HN
HN
O
N
H
O
O
O
N
H
O
NH2
(6h)
(4i)
Reaction time
(min.)
Entry
Catalyst and conditions
Yield (%)b
Ref.
[54]
[55]
[56]
[57]
This work
[52]
[53]
[51]
[58]
1
2
3
4
5
6
7
8
9
l-Proline/H2O:EtOH/25 ꢁC
SBA-Pr-SO3H/Solvent-free/140 ꢁC
TBAB/H2O/Reflux
45
15
35
120
12
40
45
60
240
30
73
90
80
92
96
83
95
88
97
95
DABCO/H2O:EtOH/25 ꢁC
SCMNPs@Urea/Py-CuCl2/H2O:EtOH/Reflux
CAN/H2O/Ultrasound
K2CO3/MW
b-Cyclodextrin/H2O/Ultrasound
Electrolys-NaBr/EtOH
SCMNPs@Urea/Py-CuCl2/H2O/Reflux
10
This work
the catalyst was extracted from the reaction mixture by permanent magnetic field, rinsed
with hot ethanol and reused for the next run. The recycled catalyst was reused at least in
six runs to catalyze the reaction without any notable decreases in the product yield
(Figure 7). To illustrate the efficiency and applicability of SCMNPs@Urea/Py-CuCl2 com-
pared to those of other reported homogeneous and heterogeneous catalysts, we
assessed the outcomes achieved for the preparation of 7-amino-5-(4-chlorophenyl)ꢂ2,4-
dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile 4i (a) and 5-(4-
chlorophenyl)ꢂ5,6-dihydro-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-trione 6 h (b) under
various conditions. The outcomes in Table 5 illustrate that our method required lower
amounts of the catalyst and provided appropriate reaction times and highest yields of
the product compared to previously reported catalysts.

JOURNAL OF COORDINATION CHEMISTRY
19
4. Conclusion
A new and reusable heterogeneous magnetic nanocatalyst, SCMNPs@Urea/Py-CuCl2,
was prepared and characterized by Fourier transform infrared spectroscopy (FTIR),
thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), energy
dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and scanning electron
microscopy (SEM). SCMNPs@Urea/Py-CuCl2 was proven to be an effective nanocata-
lyst for the synthesis of pyrano[2,3-d]pyrimidinone and pyrano[2,3-d]pyrimidine-
2,4,7-trione derivatives via two one-pot, three-component reactions under solvent-
free conditions. This strategy offers several key characteristics such as omitting toxic
solvents, high percentages of the products, less reaction times, very simple work-
up, and magnetic separation by an external magnetic field. This catalyst exhibited
suitable recyclability with no considerable decrease in the catalytic behavior even
after six runs.
Acknowledgement
This work was supported by National Natural Science Fund of China (No. 51762010), Guizhou
Provincial High-level innovative talents (2015-4006).
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by National Natural Science Fund of China (No. 51762010), Guizhou
Provincial High-level innovative talents (2015-4006).
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