An expedient synthesis of 6-amino-5-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(aryl)methyl]-1,3-dimethyl-2,4,6(1H,3H)-pyrimidinedione derivatives using Fe3O4@TiO2 nanocomposite as an efficient, magnetically separable, and reusable

Article abstract of DOI:10.1515/znb-2018-0030

An efficient methodology dealing with the Fe₃O₄@TiO₂ nanocomposite-catalyzed direct condensation reaction of 4-hydroxycoumarin, aromatic aldehydes, and 6-amino-1,3-dimethyluracil in aqueous media at room temperature is rep

Full text of DOI:10.1515/znb-2018-0030

Z. Naturforsch. 2018; aop
Sakineh Fakheri-Vayeghan, Shahrzad Abdolmohammadi* and Reza Kia-Kojoori
An expedient synthesis of 6-amino-5-[(4-hydroxy-2-oxo-
2H-chromen-3-yl)(aryl)methyl]-1,3-dimethyl-2,4,6(1H,3H)-
pyrimidinedione derivatives using Fe O4@TiO2 nanocomposite
as an efficient, magnetically separab3le, and reusable catalyst
https://doi.org/10.1515/znb-2018-0030
Received February 8, 2018; accepted April 22, 2018
moiety have been reported to show cognitive enhancing
activity [16, 17].
In the last few years, the application of metal oxide
nanoparticle (NP) catalysts in organic synthesis has
been preferably developed due to their special features
such as a high surface area with low coordination sites
[18–21]. Among them, titanium dioxide nanoparticles
(TiO2 NPs) can be used in several organic and inorganic
transformations because of its superior properties such
as high catalytic activity, nontoxicity, ease of availabil-
ity, moisture stability, and reusability [22–31]. Currently,
the magnetic nanoparticles (MNPs) doping to increase
Abstract: An efficient methodology dealing with the
Fe3O4@TiO2 nanocomposite-catalyzed direct conden-
sation reaction of 4-hydroxycoumarin, aromatic alde-
hydes, and 6-amino-1,3-dimethyluracil in aqueous media
at room temperature is reported. This new process has
been successfully applied to the synthesis of 6-amino-5-
[(4-hydroxy-2-oxo-2H-chromen-3-yl)(aryl)methyl]-1,3-di-
methyl-2,4,6(1H,3H)-pyrimidinediones in high to excellent
yields within 2–3 h.
Keywords: aqueous media; aromatic aldehydes; the utilization of heterogeneous solid catalysts have
eco-friendly protocol; Fe3O4@TiO2 nanocomposite; especially attracted great attention in organic and inor-
4-hydroxycoumarin; magnetically reusable catalyst; ganic transformations [32]. MNPs have been reported
pyrimidinediones.
to show an enormous range of various usages such as
cancer treatment [33], drug delivery [34], and simplicity
of catalyst separation. In particular, the core-shell struc-
ture of Fe3O4@TiO2 NPs with their unique characteristics
such as electronic properties, large specific surface area,
and easy magnetic separability can be used to advantage
as an efficient, easily separable heterogeneous catalyst
[35–37].
There have been a few methods for the three-compo-
nent coupling reaction of 4-hydroxycoumarin, aromatic
aldehydes, and 6-amino-1,3-dimethyluracil in the litera-
ture in which the reaction was performed under solvent-
free heating catalyzed by Zr(HSO4)4 [38] or, in another
manner, the reaction occurred under water or ethanol
refluxing using organocatalysts [39, 40]. However, these
methods have some disadvantages such as thermal reac-
tion conditions, longer reaction times, lower yields, and
effluent pollution. Therefore, it is clearly considered
that developing new and flexible procedures could be
desirable.
1 Introduction
Pyrimidinones are well-known heterocycles in the field of
synthetic organic chemistry as well as the pharmaceutical
chemistry [1]. Pyrimidinones show important biological
properties, such as antiviral, antibacterial, antihyper-
tensive, antitumor, and calcium blocker effects [2]. The
pyrimidinone is also a structural motif found in some
natural marine products such as batzelladine and caram-
bine alkaloids, which have been examined as potential
HIV-gp-120CD4 activity inhibitors [3].
Chromene and its derivatives are important core units
that display a wide range of pharmaceutical properties
such as antioxidant [4, 5], anticancer [6–9], antimicrobial
[10–13], hypotensive [14], and local anesthetic activity
[15]. Moreover, some substances containing the chromene
The purpose of this study is to investigate modi-
fied TiO2 NPs doped with Fe3O4 NPs as an efficient
heterogeneous solid catalyst for the synthesis of 6-amino-
5-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(aryl)methyl]-
1,3-dimethyl-2,4,6(1H,3H)-pyrimidinediones (4) through
a condensation reaction of 4-hydroxycoumarin (1), aro-
matic aldehydes (2), and 6-amino-1,3-dimethyluracil (3) in
aqueous media at room temperature (Scheme 1).
*Corresponding author: Shahrzad Abdolmohammadi, Department
of Chemistry, East Tehran Branch, Islamic Azad University,
P.O. Box 18735-138, Tehran, Iran, Tel.: +98-21-3359-4950,
Fax: +98-21-3358-4011, E-mail: s.abdolmohamadi@yahoo.com,
s.abdolmohamadi@iauet.ac.ir
Sakineh Fakheri-Vayeghan and Reza Kia-Kojoori: Department
of Chemistry, East Tehran Branch, Islamic Azad University,
P.O. Box 18735-138, Tehran, Iran
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ꢀS. Fakheri-Vayeghan et al.: An expedient synthesis of pyrimidinedione derivatives using Fe3O4@TiO2 nanocomposite
O
Ar
2a-l
H
Ar
O
N
O
N
OH
OH
CH3
CH3
Fe3O4@TiO2 Nanocomposite
H2O, r. t.
N
N
+
O
O
O
O
O
O
NH2
NH2
CH3
CH3
1
3
4a-l
1a, 4a Ar = C6H5, 1b, 4b Ar = 4-Br-C6H4, 1c, 4c Ar = 4-Cl-C6H4, 1d, 4d Ar = 2,4-Cl2-C6H3, 1e, 4e
Ar = 4-NC-C6H4, 1f, 4f Ar = 3-HO-C6H4, 1g, 4g Ar = 4-CH3O-C6H4, 1h, 4h Ar = 4-CH3-C6H4, 1i,
4i Ar = 3-O2N-C6H4, 1j, 4j Ar = Furan-2-yl, 1k, 4k Ar = Pyridin-4-yl, 1l, 4l Ar = Thiophen-3-yl
Scheme 1:ꢀSynthesis of 6-amino-5-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(aryl)methyl]-1,3-dimethyl-2,4,6(1H,3H)-pyrimidinedione derivatives
using Fe3O4@TiO2 NPs.
In continuation of our ongoing research in developing
nanocatalysts for the environmentally synthetic methods,
we have designed a new approach for direct condensation
reaction of 4-hydroxycoumarin, aromatic aldehydes, and
6-amino-1,3-dimethyluracil in the presence of the synthe-
sized Fe3O4@TiO2 nanocomposite as a highly active and
recyclable catalyst.
Initially, we prepared Fe3O4@TiO2 nanocatalyst using
a simple solvothermal method reported in the literature
[41]. The X-ray powder diffraction (XRD) pattern of the
synthesized nanocomposite reveals relatively weak and
broad diffraction peaks of Fe3O4 and TiO2 structure, con-
firming the lower crystallinity of the TiO2 phase in the
structure of the NPs (Fig. 1) [42].
The morphology and the average particle size of the
Fe3O4@TiO2 nanocomposite were also determined by
Fig. 2:ꢀTEM image of the synthesized Fe3O4@TiO2 NPs.
transmission electron microcopy (TEM) images (Fig. 2).
They reveal the Fe3O4@TiO2 NPs to have an average dia-
meter of 20 nm and a typical core-shell structure. The
thickness of the black Fe3O4 core and the light-colored TiO2
shell is approximately 12 and 9 nm, respectively.
The elemental composition of the catalyst was
determined using energy-dispersive spectroscopy
(EDS). The results showed the presence of Fe, Ti, C, and
Cu in the composites, with contents of 3.45%, 19.38%,
50.24%, 20.71%, and 6.22%, respectively (Fig. 3).
According to the results, the weight ratio of the synthe-
sized nanocomposite is 30:70 referred to Fe3O4 and TiO2,
respectively.
The reaction optimization was next undertaken in our
experiments, which was achieved by using 4-chloroben-
zaldehyde 2c as a model substrate for the reaction with
4-hydroxycoumarin 1, and 6-amino-1,3-dimethyluracil 3
(Table 1).
Fig. 1:ꢀXRD pattern of the synthesized Fe3O4 NPs, TiO2 NPs, and the
Fe3O4@TiO2 NPs.
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S. Fakheri-Vayeghan et al.: An expedient synthesis of pyrimidinedione derivatives using Fe3O4@TiO2 nanocompositeꢂ
aromaticaldehydeswith4-hydroxycoumarinand6-amino-
1,3-dimethyluracil by applying the optimized conditions
(Table 2). The isolated compounds (4a–l) were character-
1
13
ized by IR, H NMR, and C NMR spectroscopic data and
also by elemental analyses.
A plausible mechanism for this reaction is proposed
in Scheme 2. It is supposed that TiO2 NPs accelerate the
formation of alkene 7, which forms through a Knoevenagel
condensation between aromatic aldehydes 2 and 6-amino-
1,3-dimethyluracil 3 through intermediates 5 and 6. TiO2
NPs are also used in the subsequent Michael-type addition
of 4-hydroxycoumarin 1 to alkenes 7. Finally, product 4 is
obtained and the catalyst is released for further reactions.
To confirm the recyclability of the catalyst, after com-
pletion of the model reaction, the catalyst was success-
fully separated magnetically from the reaction mixtures as
explained in the general procedure. The recovered cata-
Fig. 3:ꢀEDS analysis of the synthesized Fe3O4@TiO2 NPs.
To demonstrate the effectiveness of the Fe3O4@TiO2 lyst was used in four subsequent runs for the same reac-
NPs as a catalyst, the model reaction was performed in tion, with only a slight decrease in activity (Fig. 4).
the absence of the catalyst. After 6 h, only 54% of product
The structures of the compounds were confirmed by
(4c) was obtained at reflux in H2O (Table 1, entry 1). In con- their satisfactory elemental analyses, IR, 1H, and 13C NMR
trast, the product (4c) was obtained in a high yield (96%) spectroscopy. Selected spectroscopic data are given in the
by treating the reaction using a catalytic amount (0.02 g) Experimental Section. The synthesized catalyst was fully
of Fe3O4@TiO2 NPs in H2O at room temperature. There was characterized by XRD, TEM, and EDS.
an improvement in the product yield when the catalyst
loading was increased from 0.01 to 0.02 g, but no signifi-
cant change was observed when the catalyst loading was 2 Conclusion
further increased to 0.03 g (Table 1, entries 2–4).
To investigate the influence of the reaction tempera- An efficient and magnetically reusable Fe3O4@TiO2
ture, the model reaction was also examined under reflux. nanocatalyst was prepared through a simple solvother-
It does not affect the product yield but it does increase the mal method. Using this catalyst, a simple, economical,
reaction rate (Table 1, entries 3 and 5).
and environmentally benign route for the synthesis of
was
In the next step, the model reaction was carried out 2-amino-6-aryl-5,6-dihydro-4(3H)-pyrimidinones
in various solvents including H2O, EtOH, CH3CN, CH2Cl2, developed. In general, the present approach offers several
and dimethylformamide (DMF). It was found that the best advantages such as simplicity of operation; use of a non-
results were obtained in water (Table 1, entries 3 and 6–9). toxic, cost-effective, and magnetically recyclable catalyst;
The scope and limitation of this new protocol was high product yields; short reaction times; and the use of
extensively evaluated for various differently substituted water as a green reaction medium.
Table 1:ꢀOptimization of the reaction conditions in the synthesis of 4c.
Entry
Catalyst
Solvent
Temperature (°C)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
None
H2O
Reflux
r. t.
6
2
54
75
96
96
96
70
62
43
79
Fe3O4@TiO2 (0.01 g)
Fe3O4@TiO2 (0.02 g)
Fe3O4@TiO2 (0.03 g)
Fe3O4@TiO2 (0.02 g)
Fe3O4@TiO2 (0.02 g)
Fe3O4@TiO2 (0.02 g)
Fe3O4@TiO2 (0.02 g)
Fe3O4@TiO2 (0.02 g)
H2O
H2O
r. t.
2
H2O
r. t.
2
1
H2O
Reflux
r. t.
EtOH
CH3CN
CH2Cl2
DMF
2.5
3
r. t.
r. t.
3
2
r. t.
aIsolated yield.
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4ꢀ ꢀS. Fakheri-Vayeghan et al.: An expedient synthesis of pyrimidinedione derivatives using Fe3O4@TiO2 nanocomposite
Table 2:ꢀSynthesis of 6-amino-5-[(4-hydroxy-2-oxo-2H-chromen-
3-yl)(aryl)methyl]-1,3-dimethyl-2,4,6(1H,3H)-pyrimidinediones 4a–l
in the presence of 0.02 g Fe3O4@TiO2.
Productꢁ Ar
ꢁ
Timeꢁ Yieldꢁ
(h) (%)a,b
M. p. (°C)
ꢁ
Obsd.ꢁ
Lit.
4a
4b
4c
4d
4e
4f
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
C6H5
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
3ꢃ
2.5ꢃ
2ꢃ
95ꢃ 190–192ꢃ 192–193 [38]
97ꢃ 234–236ꢃ 233–234 [38]
96ꢃ 191–192ꢃ 193–194 [38]
4-Br-C6H4
4-Cl-C6H4
2,4-Cl2-C6H3
4-NC-C6H4
3-HO-C6H4
4-CH3O-C6H4
4-CH3-C6H4
3-O2N-C6H4
Furan-2-yl
Pyridin-4-yl
3ꢃ
94ꢃ 290–291ꢃ
–
2ꢃ
97ꢃ 204–205ꢃ 204–206 [38]
96ꢃ 230–232ꢃ 234–236 [38]
95ꢃ 206–208ꢃ 205–207 [38]
98ꢃ 202–204ꢃ 203–205 [38]
98ꢃ 259–261ꢃ 257–259 [38]
2.5ꢃ
2.5ꢃ
3ꢃ
4g
4h
4i
2ꢃ
4j
4k
4l
2ꢃ
96ꢃ 218–220ꢃ
94ꢃ 227–229ꢃ
97ꢃ 214–216ꢃ
–
–
–
Fig. 4:ꢀRecyclability of the Fe3O4@TiO2 nanocatalyst for the synthe-
sis of 4c.
3ꢃ
Thiophen-3-ylꢃ
3ꢃ
aYields refer to pure isolated products characterized by IR, 1H, and
13C NMR spectral data and by elemental analyses. bIn all cases, the
reactions were done at room temperature in H2O (2 mL) for 2–3 h
under stirring.
3 Experimental section
3.1 Materials and methods
O
TiO2 NPs
All chemicals used in this work were purchased from
Merck and Fluka in high purity. Melting points were deter-
mined with Electrothermal 9100 apparatus. IR spectra
were obtained using a Bruker, Equinox 55, Golden Gate
N
Ar
O
H
HO
O
Ar
Fe3O4
O
N
N
HN
H
Ar
H
H
O
O
N
H2N
3
Ti
O
O
1
Micro-ATR spectrometer. H NMR and 13C NMR spectra
2
6
were recorded on a Bruker DRX-500 AVANCE spectrometer
at 500 and 125 MHz, respectively, using TMS as internal
standard and [D6]DMSO as a solvent. Elemental analy-
ses were carried out using a Foss-Heraeus CHN-O-Rapid
analyzer. The microscopic morphology of the catalyst
was extracted using a TEM technique on a Philips CM300
operating at 100 kV electron beam accelerating voltage.
Powder X-ray diffraction data were determined on a
Philips XPERT PW1800 diffractometer using CuKα radia-
tion (λꢀ=ꢀ1.5406 Å). The composition of the catalyst was
determined using EDS analysis.
Fe3O4
5
O
H2O
O
OH
Ar
Ar
O
N
N
O
N
O
H
N
H
O
1
O
O
HN
O
H
HN
Ti
O
Ti
O
O
O
Fe3O4
Fe3O4
8
7
TiO2 NPs
Fe3O4
3.2 General procedure for the preparation
of Fe3O4@TiO2 nanocomposite
Ar
O
O
N
To a magnetically stirred mixture of Fe3O4 (3 g) in 30 mL
of absolute ethanol, polyvinylpyrolidine (0.1 g) and
tetrabuthylorthotitanat (3.1 mL) were added and the result-
ing mixture was continuously stirred at 87°C for approxi-
mately 15 h. During this process, an aqueous solution of
0.15 m urea (10 mL) was added dropwise to this mixture.
In order to achieve maximum adsorption of Ti(OH)4 on
the surface of the Fe3O4 NPs, the suspension was kept
O
OH
Ar
O
N
N
O
O
OH
H2N
N
O
O
HN
H
4
Scheme 2:ꢀA plausible mechanism for the reaction of 4-hydroxy-
coumarine, aromatic aldehydes, and 6-amino-1,3-dimethyluracil
catalyzed by Fe3O4@TiO2 NPs.
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for 24 h at ambient temperature without any movement. δꢀ=ꢀ29.1 (NCH3), 31.4 (NCH3), 36.9 (C-5), 63.7 (C=C–NH2), 87.7
Afterward, the prepared magnetic nanocomposite was (C=C–OH), 105.5 (CH), 117.0, 117.8, 124.6, 125.2, 126.6, 127.2,
separated magnetically, rinsed with distilled water and 129.0, 133.3, 135.2, 139.2, 150.9, 152.8, 156.0, 164.7, 165.0,
absolute ethanol for three times, respectively, and then 166.7 ppm. – Analysis calcd. for C22H19N3O5 (405.41): C
dried at 60°C for approximately 6 h. The obtained nano- 65.18, H 4.72, N 10.36; found C 65.22, H 4.78, N 10.27.
composite was dispersed in 30 mL of ethylene glycol,
stirred for 30 min, and treated with ultrasonic vibration
for 20 min. Then, the mixture was again vigorously stirred 3.4.2 6-Amino-5-[(4-hydroxy-2-oxo-2H-chromen-
with a magnetic stirrer until a homogeneous mixture was
obtained. The mixture was then transferred to a Teflon-
sealed autoclave and heated at 200°C for 7 h to produce
3-yl)(2,4-dichlrophenyl)methyl]-1,3-dimethyl-
2,4,6(1H,3H)-pyrimidinedione (4d)
a dark-brown magnetic nanocomposite. The produced White solid, yield: 0.446 g (94%), m. p. 290°C–291°C. – IR
core-shell Fe3O4@TiO2 NPs were finally separated using (KBr): νmaxꢀ=ꢀ3438, 3359 (NH2), 3240 (OH), 1702, 1684, 1621
1
an external magnet, rinsed with absolute ethanol three (3CO), 1566, 1505 (C=C) cm−1. – H NMR (500 MHz, [D6]
times, and then dried at 80°C for 3 h in a vacuum oven.
DMSO): δꢀ=ꢀ3.15 (s, 3 H, CH3), 3.40 (s, 3 H, CH3), 5.63 (s, 1
H, H-7), 7.36 (brs, 2 H, NH2), 7.40 (m, 2 H, H-Ar), 7.43 (d,
3JHHꢀ=ꢀ7.9 Hz, 1 H, H-Ar), 7.60 (t, 3JHHꢀ=ꢀ8.0 Hz, 1 H, H-Ar), 7.76
(t, 3JHHꢀ=ꢀ7.8 Hz, 1 H, H-Ar), 7.80 (d, 3JHHꢀ=ꢀ7.0 Hz, 1 H, H-Ar),
7.84 (d, 3JHHꢀ=ꢀ7.2 Hz, 1 H, H-Ar), 13.99 (s, 1 H, OH) ppm. – 13C
NMR (125 MHz, [D6]DMSO): δꢀ=ꢀ29.1, 31.2, 36.6, 62.8, 89.1,
3.3 General procedure for the synthesis of
compounds 4a–l
A mixture of 4-hydroxycoumarine 1 (162 mg, 1 mmol), the 105.2, 117.3, 118.1, 122.2, 124.4, 130.5, 132.4, 133.4, 135.6,
aromatic aldehydes 2a–l (1 mmol; 106, 185, 141, 175, 131, 122, 136.7, 140.1, 150.9, 151.1, 156.1, 164.8, 165.0, 165.4 ppm.
136, 120, 151, 96, 107, and 112 mg, respectively), 6-amino- – Analysis calcd. for C22H17Cl2N3O5 (474.30): C 55.71, H 3.61,
1,3-dimethyluracil 3 (155 mg, 1 mmol), and Fe3O4@TiO2 NPs N 8.86; found C 55.86, H 3.49, N 8.77.
(0.02 g), in H2O (2 mL) were stirred at ambient tempera-
ture for 2–3 h (see Table 2). After completion of the reac-
tion as indicated by thin layer chromatography (eluent/ 3.4.3 6-Amino-5-[(4-hydroxy-2-oxo-2H-chromen-
ethyl acetate-petrolꢀ=ꢀ3:1), the reaction mixture was diluted
with DMF (1 mL) and the catalyst was recovered from the
reaction mixture by simply using an external magnet. For
3-yl)(4-cyanophenyl)methyl]-1,3-dimethyl-
2,4,6(1H,3H)-pyrimidinedione (4e)
reuse, the catalyst was washed with EtOH and dried in air Yellow solid, yield: 0.418 g (97%), m. p. 204°C–205°C (lit.:
at ambient temperature for several hours. The remaining 204°C–206°C [38]). – IR (KBr): νmaxꢀ=ꢀ3432, 3364 (NH2),
solution was diluted with H2O (1 mL), to yield the pure 3211 (OH), 2226 (CN), 1699, 1667, 1618 (3CO), 1571, 1507
1
products by recrystallization from this solution.
(C=C) cm−1. – H NMR (500 MHz, [D6]DMSO): δꢀ=ꢀ3.16 (s,
3 H, CH3), 3.40 (s, 3 H, CH3), 5.72 (s, 1 H, H-7), 7.37 (brs,
3
2 H, NH2), 7.40 (m, 3 H, H-Ar), 7.46 (d, JHHꢀ=ꢀ8.2 Hz, 1 H,
3
3
3.4 Selected spectroscopic data
H-Ar), 7.68 (t, JHHꢀ=ꢀ7.8 Hz, 1 H, H-Ar), 7.71 (d, JHHꢀ=ꢀ8.2 Hz,
3
2 H, H-Ar), 7.86 (d, JHHꢀ=ꢀ7.8 Hz, 1 H, H-Ar), 13.96 (s, 1 H,
13
3.4.1 6-Amino-5-[(4-hydroxy-2-oxo-2H-chromen-3-yl)
(phenyl)methyl]-1,3-dimethyl-2,4,6(1H,3H)-
pyrimidinedione (4a)
OH) ppm. – C NMR (125 MHz, [D6]DMSO): δꢀ=ꢀ29.1, 31.5,
37.4, 63.7, 87.1, 105.1, 109.5, 117.0, 117.7, 119.9, 124.0, 124.6,
125.2, 128.6, 132.8, 133.4, 145.8, 150.9, 152.9, 156.2, 164.7,
165.0, 166.5 ppm. – Analysis calcd. for C23H18N4O5 (430.42):
White solid, yield: 0.385 g (95%), m. p. 190°C–192°C (lit.: C 64.18, H 4.22, N 13.02; found C 64.23, H 4.28, N 13.12.
192°C–193°C [38]). – IR (KBr): νmaxꢀ=ꢀ3430, 3336 (NH2), 3244
1
(OH), 1689, 1668, 1619 (3CO), 1570, 1510 (C=C) cm−1. – H
NMR (500 MHz, [D6]DMSO): δꢀ=ꢀ3.17 (s, 3 H, CH3), 3.40 (s, 3.4.4 6-Amino-5-[(4-hydroxy-2-oxo-2H-chromen-
3 H, CH3), 5.65 (s, 1 H, H-7), 7.17 (d, 3JHHꢀ=ꢀ6.3 Hz, 3 H, H-Ar),
7.25 (t, 3JHHꢀ=ꢀ7.0 Hz, 2 H, H-Ar), 7.34 (brs, 2 H, NH2), 7.39 (t,
3JHHꢀ=ꢀ8.2 Hz, 1 H, H-Ar), 7.45 (d, 3JHHꢀ=ꢀ8.2 Hz, 1 H, H-Ar), 7.67
3-yl)(4-methylphenyl)methyl]-1,3-dimethyl-
2,4,6(1H,3H)-pyrimidinedione (4h)
3
3
(t, JHHꢀ=ꢀ7.6 Hz, 1 H, H-Ar), 7.86 (d, JHHꢀ=ꢀ7.6 Hz, 1 H, H-Ar), White solid, yield: 0.411 g (98%), m. p. 202°C–204°C (lit.:
13
14.00 (s, 1 H, OH) ppm. – C NMR (125 MHz, [D6]DMSO): 203°C–205°C [38]). – IR (KBr): νmaxꢀ=ꢀ3464, 3411 (NH2),
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ꢀꢀꢀꢁ
6ꢀ ꢀS. Fakheri-Vayeghan et al.: An expedient synthesis of pyrimidinedione derivatives using Fe3O4@TiO2 nanocomposite
3212 (OH), 1699, 1672, 1621 (3CO), 1570, 1508 (C=C) cm−1. 3.4.7 6-Amino-5-[(4-hydroxy-2-oxo-2H-chromen-
– 1H NMR (500 MHz, [D6]DMSO): δꢀ=ꢀ2.25 (s, 3 H, CH3), 3.16
3-yl)(3-thienylphenyl)methyl]-1,3-dimethyl-
(s, 3 H, CH3), 3.40 (s, 3 H, CH3), 5.60 (s, 1 H, H-7), 7.04 (brs,
2,4,6(1H,3H)-pyrimidinedione (4l)
3
4 H, H-Ar), 7.27 (brs, 2 H, NH2), 7.36 (t, JHHꢀ=ꢀ7.8 Hz, 1 H,
H-Ar), 7.44 (d, 3JHHꢀ=ꢀ7.8 Hz, 1 H, H-Ar), 7.66 (t, 3JHHꢀ=ꢀ7.0 Hz, Brick-red solid, yield: 0.399 g (97%), m. p. 214°C–216°C.
3
1 H, H-Ar), 7.85 (d, JHHꢀ=ꢀ7.0 Hz, 1 H, H-Ar), 13.98 (s, 1 H, – IR (KBr): νmaxꢀ=ꢀ3434, 3381 (NH2), 3217 (OH), 1710, 1685,
OH) ppm. – 13C NMR (125 MHz, [D6]DMSO): δꢀ=ꢀ21.3, 1618 (3CO), 1579, 1520 (C=C) cm−1. – 1H NMR (500 MHz, [D6]
29.1, 31.4, 36.6, 63.7, 87.9, 105.6, 117.6, 117.8, 124.6, 125.2, DMSO): δꢀ=ꢀ3.16 (s, 3 H, CH3), 3.42 (s, 3 H, CH3), 5.69 (s, 1 H,
127.1, 129.6, 132.2, 133.3, 135.5, 136.0, 150.9, 152.8, 156.0, H-7), 6.87 (d, 3JHHꢀ=ꢀ4.6 Hz, 1 H, H-Ar), 7.26 (t, 3JHHꢀ=ꢀ7.8 Hz, 1 H,
164.7, 164.9, 166.7 ppm. – Analysis calcd. for C23H21N3O5 H-Ar), 7.28 (d, 3JHHꢀ=ꢀ4.3 Hz, 1 H, H-Ar), 7.31 (d, 3JHHꢀ=ꢀ7.9 Hz,
(419.43): C 65.86, H 5.05, N 10.02; found C 65.93, H 5.12, 1 H, H-Ar), 7.35 (brs, 2 H, NH2), 7.39 (s, 1 H, H-Ar), 7.52 (d,
N 10.09.
3JHHꢀ=ꢀ7.6 Hz, 1 H, H-Ar), 7.71 (d, 3JHHꢀ=ꢀ7.6 Hz, 1 H, H-Ar), 14.11
(s, 1 H, OH) ppm. – 13C NMR (125 MHz, [D6]DMSO): δꢀ=ꢀ29.6,
31.1, 36.8, 63.0, 89.0, 104.6, 117.7, 118.6, 119.2, 124.1, 126.5,
132.4, 139.0, 140.4, 151.0, 151.7, 156.1, 163.6, 164.0, 165.8 ppm.
– Analysis calcd. for C20H17N3O5S (411.43): C 58.39, H 4.16,
N 10.21; found C 58.25, H 4.26, N 10.04.
3.4.5 6-Amino-5-[(4-hydroxy-2-oxo-2H-chromen-
3-yl)(2-furanylphenyl)methyl]-1,3-dimethyl-
2,4,6(1H,3H)-pyrimidinedione (4j)
Acknowledgments: We thank East Tehran Branch, Islamic
White solid, yield: 0.380 g (96%), m. p. 218°C–220°C. – IR
(KBr): νmaxꢀ=ꢀ3418, 3324 (NH2), 3211 (OH), 1707, 1676, 1616
Azad University, for its financial support.
1
(3CO), 1569, 1486 (C=C) cm−1. – H NMR (500 MHz, [D6]
DMSO): δꢀ=ꢀ3.15 (s, 3 H, CH3), 3.41 (s, 3 H, CH3), 5.71 (s,
1 H, H-7), 7.17 (m, 3 H, H-Ar), 7.29 (brs, 2 H, NH2), 7.30 (t,
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Z. Naturforsch.ꢂ
ꢂ2018 | Volume x | Issue x(b)
Graphical synopsis
Sakineh Fakheri-Vayeghan, Shahrzad
Abdolmohammadi and Reza Kia-Kojoori
An expedient synthesis of 6-amino-5-
[(4-hydroxy-2-oxo-2H-chromen-3-yl)
(aryl)methyl]-1,3-dimethyl-2,4,6(1H,3H)-
pyrimidinedione derivatives using Fe3O4@
TiO2 nanocomposite as an efficient, mag-
netically separable, and reusable catalyst
https://doi.org/10.1515/znb-2018-0030
Z. Naturforsch. 2018; x(x)b: xxx–xxx
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