Ultrasound-promoted an efficient method for the one-pot synthesis of indeno fused pyrido[2,3-d]pyrimidines catalyzed by H3PW12O40 functionalized chitosan@Co3O4 as a novel and green catalyst

Article abstract of DOI:10.1016/j.jorganchem.2018.10.028

A novel magnetically recoverable nanocomposite including Co₃O₄/chitosan/H₃PW₁₂O₄₀ (Co₃O₄/CS/PWA) as a heterogeneous catalyst was prepared using a facile synthetic method and characterized by FT-IR, XRD, SEM, VSM and EDX. A simple, efficient and rapid synthesis of indeno[2?,1?:5,6]pyrido[2,3-d]pyrimidines was accomplished in excellent yields via one-pot three-component reaction of 1,3-dimethyl-6-aminouracil, aryl aldehydes and 1,3-indandione in the presence of amount of Co₃O₄/CS/PWA catalyst under ultrasound irradiation. Then, the catalyst was recovered with an external magnet and reused several times without significant loss of reactivity.

Full text of DOI:10.1016/j.jorganchem.2018.10.028

Accepted Manuscript
Ultrasound-promoted an efficient method for the one-pot synthesis of indeno fused
pyrido[2,3-d]pyrimidines catalyzed by H PW
3
as a novel and green catalyst
O
functionalized chitosan@Co O
3 4
12 40
Javad Safari, Mona Tavakoli, Mohammad Ali Ghasemzadeh
PII:
S0022-328X(18)30783-6
DOI:
https://doi.org/10.1016/j.jorganchem.2018.10.028
JOM 20613
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 5 September 2018
Revised Date: 24 October 2018
Accepted Date: 28 October 2018
Please cite this article as: J. Safari, M. Tavakoli, M.A. Ghasemzadeh, Ultrasound-promoted an efficient
method for the one-pot synthesis of indeno fused pyrido[2,3-d]pyrimidines catalyzed by H PW
O
12 40
3
functionalized chitosan@Co O as a novel and green catalyst, Journal of Organometallic Chemistry
3 4
(2018), doi: https://doi.org/10.1016/j.jorganchem.2018.10.028.
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ACCEPTED MANUSCRIPT
An efficient three-component reaction of aromatic aldehydes, 1,3-dimethyl-6-aminouracil
and 1,3-indandione in the presence of a novel magnetically recoverable nanocomposite
H3PW12O40 immobilized Co3O4/chitosan led to a synthesis of a new class of
indeno[2ʹ,1ʹ:5,6]pyrido[2,3-d]pyrimidines derivatives under ultrasound irradiation.

ACCEPTED MANUSCRIPT
Ultrasound-promoted an efficient method for the one-pot synthesis of indeno fused
pyrido[2,3-d]pyrimidines catalyzed by H3PW12O40 functionalized chitosan@Co3O4 as a
novel and green catalyst
a
Javad Safari⁄ , Mona Tavakolia, Mohammad Ali Ghasemzadehb
aDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan
87317, Iran
bDepartment of Chemistry, Qom Branch, Islamic Azad University, Qom, Iran
E-mail addresses: safari_jav@yahoo.com, safari@kashanu.ac.ir
Abstract
A novel magnetically recoverable nanocomposite including Co3O4/chitosan/H3PW12O40
(Co3O4/CS/PWA) as a heterogeneous catalyst was prepared using a facile synthetic method and
characterized by FT-IR, XRD, SEM, VSM and EDX. A simple, efficient and rapid synthesis of
indeno[2ʹ,1ʹ:5,6]pyrido[2,3-d]pyrimidines was accomplished in excellent yields via one-pot
three-component reaction of 1,3-dimethyl-6-aminouracil, aryl aldehydes and 1,3-indandione in
the presence of amount of Co3O4/CS/PWA catalyst under ultrasound irradiation. Then, the
catalyst was recovered with an external magnet and reused several times without significant
loss of reactivity.
Key words: Heterogeneous catalyst, Co3O4/CS/PWA, Three-component reaction, Ultrasound
Irradiation, Indeno[2ʹ,1ʹ:5,6]pyrido[2,3-d]pyrimidine
1. Introduction
Nano catalysts have attracted considerable attention in catalysis science. This attention can
be attributed to their efficient recovery characteristics, recycling potential, highly stability,
selectivity, activity and durability in the catalytic activities [1]. These characteristics are
affected by size, shape, morphology, composition, electronic structure and composition and can
also affect the catalytic activity of a material [2].
Recently, magnetic nanoparticles (MNPs) has been applied as an effective heterogeneous
catalyst with a number of advantages such as control of nanoparticle size, shape and activity,
enhanced selectivity, active sites, ease of availability, excellent thermal stability and chemical
inertness [3-7]. In addition, these magnetic nanoparticles reduces energy consumption and
saves time in achieving catalyst recovery through facile separation from the reaction mixture by
an external magnet [8,9]. Cobalt oxide nanoparticles (Co3O4 NPs) are currently attracting
enormous interest owing to their unique size and shape-dependent properties and potential
applications in battery cathodes, magnetic materials, electrochromic devices, solid-state sensors
and catalysis [10-14].
Chitosan is a random copolymer of glucosamine and an N-acetyl glucosamine linked,
obtained after partial deacetylation of chitin, which is a byproduct of seafood processing
industries [15-16]. It is a natural, commercially available, eco-friendly, chemically stable,
biocompatibility, non-toxicity, antioxidant properties, low immunogenicity and inhibits the
growth of a wide variety of bacteria and fungi [17-19]. The amino and hydroxyl groups in the
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repeating glycosidic residue provides various coordination sites for chemical modifications and
a suitable matrix to synthesize magnetic composites [20].
The materials such as Fe3O4 [15,16,18], Cu [21-23], Ag [24], Ni nanoparticles [25] and
magnetic carbon nanotube [26] are as a core in the network of the cross-linked chitosan,
extensively prepared and used in catalytic reaction therefore employed for carbonylation,
oxidation, C–C coupling and multicomponent reactions [16,27].
Heteropolyacids (HPAs) are important class of compounds that are widely used as catalyst
for the synthesis of fine and specific chemicals, medicine, and materials science [28] .These
compounds possess unique properties such as high thermal stability, high proton mobility, high
oxidation potential, easy work-up procedures, safety, easy separability, little waste and easy
filtration [29-32]. HPAs are well known super-strong acids for both homogeneous and
heterogeneous acid-catalyzed reactions [33]. H3PW12O40 (12-phosphotungstic acid; PWA), the
free acidic forms of HPWs with Keggin structure, is considered for chemical conversions
because of their strong Brønsted acidity and higher stability [34].
Ultrasonic-assisted organic synthesis (UAOS) as a green synthetic approach is a promising
technique that is being used in the chemistry process which requires drastic conditions or
prolonged reaction time [10,35]. UAOS can be extremely efficient and it is applicable to an
approach are enhanced reaction rates, formation of purer products in high yields, easier
manipulation and environmental friendliness which compared with traditional methods [16,36].
Pyrido[2,3-d]pyrimidines are an important class of heterocyclic compounds annulated uracil
with wide range of biological and pharmacological activities, such as anti-folate,
anticonvulsants, anti-bacterial, antimicrobial, anti-inflammatory, anti-aggressive activity, anti-
leishmania and inhibitors of cyclin-dependent kinases [37,38].
The synthesis of indeno[2ʹ,1ʹ:5,6]Pyrido[2,3-d]pyrimidines have already been reported via
multicomponent reactions in the presence of β-cyclodextrin-propyl sulfonic acid [39], p-toluene
sulfonic acid [40], indium trichloride [41], zirconium hydrogen sulfate [42] and Fe3O4@SiO2–
SO3H [43] as catalyst.
In this work, we designed the construction of a magnetically recoverable acid
nanocomposite, in which H3PW12O40 (12-phosphotungstic acid) molecules are immobilized
into the network of the cross-linked chitosan with the paramagnetic Co3O4 nanoparticles as a
novel, green and recyclable catalyst (Scheme 1).
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Scheme 1. Preparation process of Co3O4/chitosan/HPA
2. Experimental
All chemicals used in this work from Merck or Aldrich Chemical Company.
FT-IR spectra were obtained with KBr pellets in the range 400–4000 cm-1 with a Perkin-Elmer
1
550 spectrometer. H NMR spectra was obtained using a Bruker DRX-400 AVANCE
spectrometer at 400 MHz. Melting points were determined using an Electrothermal 9100
apparatus and are uncorrected. Nanostructures were characterized using a Holland Philips X
ray powder diffraction (XRD) diffractometer (Cu K, radiation, k = 0.154056 nm), at a scanning
speed of 2 min1 from 10 to 100 (2Ɵ). Microscopic Morphological characteristics were
observed By SEM (LEO 1455VP). Magnetic properties were characterized by a vibrating
sample magnetometer (VSM, MDKFD, University of kashan, Kashan, Iran) at room
temperature. The compositional analysis was done by energy-dispersive analysis of X-ray
(EDX, Kevex, Delta Class I). Sonication was performed in a Shanghai Branson-BUG40-06
ultrasonic cleaner (with a frequency of 40 kHz and anominal power of 200 W).
2.1. Preparation of Co3O4 Nanoparticles
Co3O4 MNPs were prepared according to previously reported procedure by Vela et al. with
some modifications [44]. First, cobalt nitrate hexahydrate (8.60 g) was dissolved in 100 mL of
ethanol the mixture was vigorously stirred. Then, the mixture was heated to 50 °C and kept for
30 min. Finally, oxalic acid (2.14 g) was added quickly to the solution and the reaction mixture
was stirred for 2 h at 50 °C. The formed precipitate including cobalt (II) oxalate was collected
by centrifuge, followed by calcination at 400 °C for 2 h to produce the Co3O4 nanoparticles.
2.2. Preparation of H3PW12O40
H3PW12O40 was synthesized by the addition of Na2WO4 (50 g) in 75 ml H2O to a solution
of 1 ml of H3P04 (85%). The solution was stirred and heated to boiling point followed by
addition of HCl. The hot mixed liquid was filtrated through Buchner funnel and transferred to a
separator funnel after it has been cooled at room temperature and added 30 ml ether. And
finally, it was placed in thermostatic oven with a temperature of 110 °C and dried until the
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solvent had been evaporated, obtained H3PW12O40 [45]. Principle can be expressed as reaction
equation (1):
PO43- + 12WO42- + 24 H+
H3PW12O40 + 12 H2O
(1)
2.3. Procedure for the preparation of Co3O4/chitosan/HPA
For the synthesis of chitosan–Co3O4 core-shell (CS-Co3O4), 0.5 g of Co3O4 nanoparticles
was added to a solution containing 0.5 g of chitosan in 50 mL of acetic acid (0.05 M) solution.
The mixture was sonicated and heated at 40 °C for 0.5 h, After that, 12 ml of 4 wt%
glutaraldehyde aqueous solutions was added drop by drop under stirring and the reactant
mixtures were heated and stirred for 1 h at 40 °C and 1 h at 60 °C. The cross-linking chitosan-
coated Co3O4 (CS-Co3O4) was formed in the process. Then, 20 ml of aqueous solution
containing H3PW12O40 (12-phosphotungstic acid) (0.045 g mL−1) was added to the mixture and
stirred for 0.5 h at 60 °C. Finally, the black gel products were separated by centrifugation,
washed several times with deionized water and ethanol and dried in vacuum at 60 °C for 8 h.
2.4. General procedure for the synthesis of indeno fused pyrido[2,3-d]pyrimidines
A mixture of 1,3-dimethyl-6-aminouracil (1 mmol), aryl aldehyde (1 mmol), 1,3-
indandione (1 mmol) in EtOH (5 ml) was irradiated in the ultrasonic bath in the presence of
Co3O4/CS/HPA (0.005 g). After the completion of the reaction (monitored by TLC), the
reaction was allowed to cool and the magnetic catalyst was removed by an external magnet.
The obtained solid was filtered, cooled and washed with water and ethanol to afford the desired
pure product.
2.5. Spectral data for new compounds
2.5.1. 4-(1,3-dimethyl-2,4,6-trioxo-2,3,4,5,6,11-hexahydro-1H-indeno[2',1':5,6]pyrido[2,3-
d]pyrimidin-5-yl)benzonitrile (4i)
1
m.p = > 300 ºC; Yellow solid; IR (KBr, cm-1): 3424, 2958, 1715, 1661, 1573, 1504; H NMR
(400 MHz, DMSO-d6) δ: 3.14 (s, 3H, CH3), 3.75 (s, 3H, CH3), 7.45 (d, J= 6.8 Hz, 2H, Ar-H),
7.60-7.66 (m, 2H, Ar-H), 7.78 (t, J= 6.1 Hz, 1H, Ar-H), 7.88 (d, J= 6.4 Hz, 2H, Ar-H), 7.99 (d,
J= 6.0 Hz, 1H, Ar-H) ppm; Anal. Calcd (%) for C23H14N4O3: C, 70.05; H, 3.58; N, 14.21.
Found: C, 69.9; H, 3.69; N, 14.13.
2.5.2. 5-(3-bromophenyl)-1,3-dimethyl-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine-
2,4,6(3H)-trione (4j)
1
m.p = > 300 ºC; Yellow solid; IR (KBr, cm-1): 3417, 3067, 1718, 1673, 1567, 1500; H NMR
(400 MHz, DMSO-d6) δ: 3.14 (s, 3H, CH3), 3.73 (s, 3H, CH3), 7.23 (d, J= 7.6 Hz, 1H, Ar-H),
7.36 (t, J= 7.6 Hz, 1H, Ar-H), 7.44 (s, 1H, Ar-H), 7.61 (t, J= 7.2 Hz, 3H, Ar-H), 7.77 (t, J= 7.2
Hz, 1H, Ar-H), 7.97 (d, J= 7.2 Hz, 1H, Ar-H) ppm; Anal. Calcd (%) for C22H14BrN3O3: C,
58.95; H, 3.15; N, 9.37. Found: C, 58.90; H, 3.18; N, 9.33.
2.5.3. 5-(2-chlorophenyl)-1,3-dimethyl-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine-
2,4,6(3H)-trione (4k)
1
m.p = > 300 ºC; Orange solid; IR (KBr, cm-1): 3433, 2922, 1700, 1659, 1629, 1504; H NMR
(400 MHz, DMSO-d6) δ: 3.06 (s, 3H, CH3), 3.59 (s, 3H, CH3), 5.18 (s, 1H, CH), 7.12 (d, J= 7.6
Hz, 1H, Ar-H), 7.18 (t, J= 7.2 Hz, 1H, Ar-H), 7.22 (d, J= 7.2 Hz, 1H, Ar-H), 7.26 (d, J= 8.0
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Hz, 1H, Ar-H), 7.33 (t, J= 7.2 Hz, 2H, Ar-H), 7.47 (t, J= 7.2 Hz, 1H, Ar-H), 7.87 (d, J= 6.8 Hz,
1H, Ar-H) ppm; Anal. Calcd (%) for C22H14ClN3O3: C, 65.44; H, 3.49; N, 10.41. Found: C,
65.41; H, 3.52; N, 10.39.
3. Results and discussion
The magnetically heterogeneous nanocomposite Co3O4/CS/HPA, is characterized by
Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy
(SEM), vibrating sample magnetometer (VSM) and energy-dispersive X-ray spectroscopy
(EDX). The FTIR spectra of Co3O4 nanoparticles, chitosan, H3PW12O4, magnetic Co3O4/CS/
HPA catalyst are shown in Fig. 1. The two strong absorption bands at 567 and 664 cm–1 are
attributed to the vibrations of Co–O in Co3O4 nanoparticles (Fig 1a). In Fig. 1b the main bands
of chitosan were characterized by the following absorption bands: coaxial stretching vibration
of O─H overlapped with N–H stretching visible at 3000–3750 cm−1, C–O of hydroxyl group at
1383 cm-1. Also, the C─H axial stretching band appears at 2922 cm−1 [15-18]. The
characteristic bands of H3PW12O40 are clearly observed at P–O stretching at 1079 cm−1, a band
at 983 cm−1 corresponding to W=O and band at 891 and 792 cm-1 due to W–OC–W and W–Ob–
W respectively (Fig. 1c) [46-47]. In the FTIR spectrum of Co3O4/CS/HPA, the absorption
peaks of Co–O bonds at 569 and 663 cm−1 indicates the successful cross-linking of chitosan on
the Co3O4 particle surface. The stretching vibration characteristic peak of C=N at 1628 cm−1 is
due to cross-linking reaction by glutaraldehyde. The broad band at 3150–3700 cm−1 is due to
the hydroxyl (O–H) stretching in Co3O4/CS/HPA. In addition, the characteristic IR bands of
H3PW12O40 were clearly observed in the IR spectrum of the as-prepared Co3O4/CS/HPA
catalyst at 1079, 954, 889 and 807 cm−1. The results are consistent with the synthesis design,
and confirm that H3PW12O40 are highly dispersed on the net cross-linking chitosan in the
singular molecule form (Fig. 1d).
Fig. 1. FT-IR spectra of Co3O4 NPs (a), chitosan (b), H3PW12O40 (c), Co3O4/CS/HPA (d)
The X-ray diffraction patterns of Co3O4 nanoparticles and Co3O4/CS/HPA are shown in
Fig. 2. The particle size of Co3O4 nanoparticles is determined to be about 25 nm by Scherrer’s
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equation (K = 0.90). As can be seen, the XRD pattern Co3O4/CS/HPA catalyst reveals the same
diffraction peaks to that of bare Co3O4.
Fig. 2. X-ray diffraction of Co3O4 NPs (a) and Co3O4/CS/HPA catalyst (b)
The morphology, size and shape of the catalyst were studied by scanning SEM (Fig. 3). It
showed that magnetic Co3O4/CS/HPA nanocomposite are nearly spherical with diameter about
20-40 nm, which is completely agreement with the XRD spectrum.
Fig. 3. SEM images of Co3O4/CS/HPA catalyst
The magnetic properties of the uncoated Co3O4 and Co3O4/CS/HPA nanocomposite were
measured with VSM (Fig. 4). There are no hysteresis, coercivity and remanence in bare Co3O4
and Co3O4/CS/HPA samples at room temperature that show their typical superparamagnetic
properties. The decrease in magnetic saturation for Co3O4/CS/HPA is attributed to the cover of
CS/HPA hybrid materials shells on the surface of magnetic Co3O4 MNPs cores.
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Fig. 4. VSM magnetization curves of the Co3O4 NPs (a) and Co3O4/CS/HPA (b)
The chemical purity of the catalyst was tested by energy-dispersive X-ray spectroscopy
(EDX). As shown in Fig. 5, the EDX spectrum shows the presence of Co, W, C, O, N and P as
the elements of the nanocomposites.
Fig. 5. EDX spectra of Co3O4/CS/HPA catalyst
In this research, we report an efficient synthesis of indeno[2ʹ,1ʹ:5,6]pyrido[2,3-d]
pyrimidines in high yields via the cyclocondensation reactions in the presence of Co3O4/CS/
HPA as an efficient catalyst under ultrasound irradiation. In order to optimize the reaction
conditions, the model reaction was carried out using 1,3 -indandione 1, aldehyde (R= 4-Cl), 2
and 1,3-dimethyl-6-aminouracil 3 under various conditions by using ultrasound irradiation
(Scheme 2). The reaction conditions were optimized on the basis of the solvent, catalyst, and
different intensity power of ultrasonic for the synthesis of indeno[2ʹ,1ʹ:5,6]pyrido[2,3-
d]pyrimidine.
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Scheme 2. Three-component synthesis of indeno[2ʹ,1ʹ:5,6]pyrido[2,3-d]pyrimidine by
Co3O4/CS/HPA nanocomposite
To determine the effect of different solvents on the model reaction, the reaction was carried
out in a range of different solvents such as: MeOH, EtOH, CH2Cl2, CCl4, and CH3CN. It was
found that CCl4 was completely ineffective for the reaction, with no trace amount of the
product being detected. CH2Cl2 and CH3CN were also unsuitable for the reaction, affording
only 28% and 48% conversion after 30 min, respectively. MeOH offered better performance
than CH2Cl2 and CH3CN, with 75% conversions, being observed after 30 min. Among these
solvents, EtOH exhibited the best performance, and should be the solvent of choice for the
reaction conversion to 95% after 30 min using the Co3O4/CS/HPA catalyst under ultrasound
irradiation (Fig. 6).
CCl4
CH2CL2
CH3CN
MeOH
EtOH
100
75
50
25
0
0
10
15
20
30
Time (min)
Fig. 6. Effect of different solvents on model reaction
After this, we have studied the effect of intensity power of ultrasonic on the model reaction.
The model study was carried out at 20%, 30%, 40% and 50% of the rate power of the
ultrasonic bath (40, 60, 80 and 100 W).
The results are shown in Fig. 7. Generally, the enhance in the acoustic power could
enhance the number of active cavitation bubbles and also the size of the individual bubbles.
Both increases can be supposed to result in an increase in the maximum collapse temperature
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and the respective reaction could be done faster. It can be seen from Fig. 7 that increase of
ultrasonic power led to relatively higher yield and shorter reaction time before the ultrasound
power intensity reached 40%, and then the yield decreased slightly with increasing ultrasound
power intensity.
%20
%30
%40
%50
100
75
50
25
0
0
10
15
20
30
Time (min)
Fig. 7. Effect of intensity power of ultrasonic on the synthesis of indeno[2ʹ,1ʹ:5,6]pyrido[2,3-d]
pyrimidine
In continuation of our research, the model reaction was carried out in the range of 0 to
0.008 g of Co3O4/CS/HPA nanocomposite. According to Fig. 8, no product was obtained in the
absence of the catalyst, confirming the necessity of using the Co3O4/CS/HPA for the reaction
conditions. It was found that the optimum amount of catalyst was 0.005 g catalyst which
proceeded readily to 95% conversion after 30 min. Also the results indicate that decreasing in
the amounts of the catalyst from 0.005 g led to decrease in yield of the reaction. It should be
noted that increasing of the catalyst did not show any significant changes in yield and time of
reaction.
Fig. 8. Effect of amount catalyst on reaction yield
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In order to study the effect of various catalysts under ultrasound irradiation, catalytic
behaviors of five types of catalysts such as TiO2 NPs, SiO2 NPs, Co3O4 NPs, MgO NPs and
Co3O4/CS/HPA were investigated on the model reaction (Fig. 9). When TiO2 NPs, SiO2 NPs,
Co3O4 NPs and MgO NPs was used as the catalyst, the reaction could proceed to 53%, 45%,
64%, 55% conversion after 30 min, respectively. The result of this study showed that
compound provided high yield in the presence of the Co3O4/CS/HPA nanocomposites under
ultrasound irradiation.
100
75
50
25
0
Catalyst
Fig. 9. Effect of various catalysts on the model study
A plausible mechanism for the reaction by catalysis of Co3O4/CS/HPA nanocomposite is
shown in scheme 3. We suppose that Co3O4/CS/HPA behave as strong acid by increasing the
electrophilicity of carbonyl groups and intermediates, through formation of a strong coordinate
band. As shown in scheme 3, first, the activated carbonyl (1) reacts with activated 1,3-
indandione (2) to afford the intermediate A which followed by a Michael-type addition reaction
with 1,3-dimethyl-6-aminouracil (3) to produce the intermediate B. Subsequently,
intramolecular cyclization, dehydration and aromatization on intermediate provided the final
product.
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Scheme 3. Plausible mechanism of the reaction
To study the scope of this procedure, we have synthesized indeno[2ʹ,1ʹ:5,6]pyrido[2,3
d]pyrimidine derivatives by using a wide range of aromatic aldehydes containing electron-
withdrawing and electron-donating groups in the presence of 0.005 g of Co3O4/CS/HPA
nanocomposite. The results in Table 1 indicate that the aryl aldehydes with electron- donating
groups required prolonged reaction time to give the yields, while the aryl aldehydes with
electron- withdrawing groups reacted very smoothly and produced high yields of products.
Table 1. Synthesis of indeno[2ʹ,1ʹ:5,6]pyrido[2,3-d]pyrimidine derivatives by using
Co3O4/CS/HPA nanocomposite as catalyst under ultrasound irradiationa
Entry
R
H
Product
4a
Time (min)
Yield of 4 (%)b
1
2
3
30
25
30
86
90
80
4-Br
4b
4-i-Propyl
4c
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4
5
2-NO2
4-CH3
4-NO2
3-NO2
4-Cl
4d
4e
4f
25
30
30
25
30
20
25
30
83
88
92
85
95
90
86
81
6
7
4g
4h
4i
8
9
4-CN
3-Br
10
4j
11
2-Cl
4k
a Reaction conditions: various aldehydes (1 mmol), 1,3-indandione (1 mmol) and 1,3-
o
dimethyl-6- aminouracil (1 mmol), catalyst (0.005 g) at 40 C under ultrasound
irradiation.
b Yields of isolated products.
In order to investigate the reusability of the catalyst, the model reaction was repeated using
recovered Co3O4/CS/HPA core–shell nanocomposite under the optimized reaction conditions.
After completing the model reactions, the products were removed by filtration. The catalyst
was separated magnetically and then washed with water and ethanol. As shown in Fig. 10, we
observed that the separated catalyst could be used for six cycles with a slightly decreased
activity.
100
80
60
40
20
0
1
2
3
4
5
6
Run
Fig. 10. Reusability of the Co3O4/CS/HPA nanocomposite
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4. Conclusions
In summary, an efficient method for the synthesis of the indeno[2ʹ,1ʹ:5,6]pyrido[2,3-
d]pyrimidines is reported by the treatment of aryl aldehydes, 1,3-indandione with 1,3-dimethyl-
6-aminouracil in the presence of Co3O4/CS/HPA nanocomposite under ultrasonic irradiation.
This method provides several advantages such as clean reaction conditions, simple work-up
procedure, shorter reaction time, excellent yields, and reusability of the catalyst. We expect this
method will find extensive applications in the field of combinatorial chemistry, diversity-
oriented synthesis and sonochemistry and drug discovery.
Acknowledgments
We gratefully acknowledge the financial support from the Research Council of the University
of Kashan for supporting this work.
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A simple, efficient and rapid synthesis of indeno[2ʹ,1ʹ:5,6]pyrido[2,3-d]pyrimidines
catalysts can be magnetically separated from the reaction with an external magnet
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The recovered catalysts and reused several times without significant loss of reactivity
clean reaction conditions and simple work-up procedure
shorter reaction time and excellent yields of products