Copper (II)-supported polyethylenimine-functionalized magnetic graphene oxide as a catalyst for the green synthesis of 2-arylquinazolin-4(3H)-ones

Article abstract of DOI:10.1007/s11164-018-3420-2

A novel copper (II) catalyst supported on polyethylenimine-functionalized magnetic graphene oxide (denoted Cu@PEI-MGO) has been developed and applied for the cyclization of benzylacetamide with 2-aminobenzamide to afford 2-arylquinazolin-4(3H)-ones in acetonitrile as an inexpensive, non-toxic and reusable solvent medium. Cu@PEI-MGO was characterized by transmission electron microscopy, scanning electron microscopy, thermo-gravimetric analysis, and Fourier-transform infra-red spectroscopy.

Full text of DOI:10.1007/s11164-018-3420-2

Res Chem Intermed
https://doi.org/10.1007/s11164-018-3420-2
Copper (II)-supported polyethylenimine-functionalized
magnetic graphene oxide as a catalyst for the green
synthesis of 2-arylquinazolin-4(3H)-ones
Mohammad Hosein Sayahi1 Saeed Bahadorikhalili2
•
•
Seyyed Jafar Saghanezhad3
Mohammad Mahdavi4
•
Received: 6 November 2017 / Accepted: 27 March 2018
Ó Springer Science+Business Media B.V., part of Springer Nature 2018
Abstract A novel copper (II) catalyst supported on polyethylenimine-functional-
ized magnetic graphene oxide (denoted Cu@PEI-MGO) has been developed and
applied for the cyclization of benzylacetamide with 2-aminobenzamide to afford
2-arylquinazolin-4(3H)-ones in acetonitrile as an inexpensive, non-toxic and reu-
sable solvent medium. Cu@PEI-MGO was characterized by transmission electron
microscopy, scanning electron microscopy, thermo-gravimetric analysis, and
Fourier-transform infra-red spectroscopy.
Keywords Copper (II) Á Immobilized catalyst Á Polyethylenimine Á Magnetic
graphene oxide Á Quinazolinone
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11164-
018-3420-2) contains supplementary material, which is available to authorized users.
&
&
Mohammad Hosein Sayahi
sayahymh@pnu.ac.ir
Seyyed Jafar Saghanezhad
Saghanezhad@acecr.ac.ir
1
2
Department of Chemistry, Payame Noor University (PNU), P.O. Box 19395-3697, Tehran, Iran
School of Chemistry, College of Science, University of Tehran, P.O. Box 14155-6455 Tehran,
Iran
3
4
ACECR-Production Technology Research Institute, Ahvaz, Iran
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical
Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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M. H. Sayahi et al.
Introduction
Copper is an important catalyst due to its high activity and selectivity in modern
organic synthesis [1–3]. Facile separation and recovery of catalysts is a significant
issue, while immobilization on nanoparticles is a favorable approach. Among
different nanoparticles which are used as supports, magnetic graphene oxide (MGO)
has attracted interest because of its high surface area, stability, easy separability and
unique potential technical applications [4–6]. Poly(ethyleneimine) (PEI) is a
nitrogen-rich and water-compatible polymer with unique properties including
physical and chemical stabilities, good water solubility, and high content of
functional groups. Due to these advantages, it has attracted interest for the
functionalization of nanoparticles [7–9].
Quinazoline-4(3H)-one core is an important biologically active nitrogen-
containing heterocyclic scaffold because of its extensive biological and pharma-
cological activities. Anticancer [10], antimicrobial [11], anti-inflammatory [12],
anticonvulsant [13], anti-ulcer [14], antibacterial [15], and antivirus [16] properties
have been reported for these heterocyclic compounds. Additionally, the quinazo-
line-4(3H)-one subunit has been widely applied in medicinal chemistry.
Methaqualone, luotonin, piriqualone and bouchardatine are a few illustrative
examples of potentially pharmacologically active quinazolineones (Fig. 1) [17].
Regarding the remarkable biological activities of quinazolines, it is not surprising
that various procedures for their preparation have been reported in the literature.
The typical approaches generally include condensation of 2-aminobenzamide with
aldehydes, alkyl halides, primary amines or alcohols, reductive cyclization of
2-nitrobenzamide with aldehydes or primary alcohols, reaction of isatoic anhydride
with amidoximes, or ammonium salts and aldehydes, and so on [18]. Also, the
synthesis of quinazolines under oxidation conditions by reaction of 2-halo or
2-aminobenzamides with benzylic substrates, such as benzyl halides or benzyl
amines under copper-promoted aerobic oxidation, or by use of H2O2 as an oxidant,
has recently been explored [19]. Thus, we wish to develop these procedures for the
synthesis of quinazolin-4(3H)-ones using sequential oxidative cyclization of
Fig. 1 Examples of
pharmacologically active
quinazolineones
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Copper (II)-supported polyethylenimine-functionalized…
primary benzyl amines with 2-aminobenzamide in acetonitrile as an appropriate and
convenient reaction medium.
We have previously reported several efforts for the development of efficient and
eco-friendly methodologies for the preparation of biologically active target
molecules [20–22], and also on extending methodologies based on transition
metal-catalyzed reactions [23–28]. In continuation of our previous efforts, we here
introduce a novel copper (II) catalyst supported on polyethylenimine-functionalized
magnetic graphene oxide, Cu@PEI-MGO. The catalyst has been used for the
synthesis of 2-arylquinazolin-4(3H)-ones 3a–j by reaction of 2-aminobenzamide 1
with benzylacetamide 2a–j in acetonitrile as a green solvent in reflux conditions
with N-hydroxyphthalimide (NHPI) and O2 as oxidant (Scheme 1).
Experimental
All chemicals were purchased from Merck and Fluka. All yields refer to isolated
products. Melting points were determined in a capillary tube and are not corrected.
The progress of the reactions was followed by TLC using silica gel SILG/UV 254
1
and 365 plates. H and 13C NMR spectra were recorded on a Brucker (Rheinstetten,
Germany) NMR spectrometer at 500 and 125 MHz using tetramethylsilane (TMS)
as the internal standard. IR spectra of the compounds were obtained on a FT-IR
Magna 550 spectrographs (KBr disks) (Nicolet, Madison, WI, USA). All products
1
are known compounds and were characterized by comparing the IR, H and 13C
NMR spectroscopic data and their melting points with the literature values. A TGA
diagram was recorded via TGA Q500 V20.13 Build 39. SEM images were recorded
by a HITACHI S-4160 instrument. A CM30 300 kV instrument was used to record
TEM images.
Preparation of magnetic graphene oxide
According to our previous report, the GO was manufactured from graphite using a
modified Hummer’s method [27]: briefly, 1 g of graphite powder was added to a
continuously stirred solution of 50 mL H2SO4 98% in an ice bath, then 2 g KMnO4
was gently added to it. It should be noted that the rate of addition was carefully
controlled to avoid a sudden increase in the mixture temperature. The reaction
mixture stirred for 2 h at temperatures below 10 °C, followed by another 1 h at
35 °C. Then, the reaction mixture was diluted with 50 mL of deionized water in an
Scheme 1 Cu@PEI-MGO-promoted synthesis of 2-arylquinazolin-4(3H)-ones
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M. H. Sayahi et al.
ice bath and the temperature was kept below 100 °C. After 1 h of stirring, the
mixture was further diluted to 150 mL with deionized water. Then, 10 mL of H2O2
30% was added to the mixture which changed its color to brilliant yellow. The
resulting solid was separated by centrifuging and washed thoroughly with 5% HCl
aq. solution and deionized water to neutralize it. Finally, the resultant product was
dried at 60 °C for 24 h.
For the preparation of the magnetic graphene oxide (MGO), MGO nanosheets
were synthesized by co-precipitation of Fe3? and Fe2? in the presence of GO [27].
The solution of Fe3? and Fe2? was prepared in a 2:1 mol ratio. Next, 50 mg of GO
was dispersed in 40 mL of water by sonication for 45 min. Then, a 50-mL solution
of FeCl3 (1 g) and FeCl2 (375 mg) in deionized water was added to the latter
solution. The reaction temperature was raised to 85 °C and ammonia solution 30%
was added to it, increasing the pH to 10. After 45 min of vigorous stirring, the
solution was cooled to room temperature, and the obtained black precipitate was
centrifuged at 6000 rpm for 10 min, washed thoroughly with deionized water and
dried at 60 °C for 24 h.
Preparation of polyethylenimine-functionalized magnetic graphene oxide
(PEI-MGO)
To produce the polyethylenimine-functionalized magnetic graphene oxide (PEI-
MGO) nanosheets, the necessary carboxylic acid functional groups were introduced
by taking 50 mg of MGO in deionized water (4 mg mL-1) and sonicating it for 1 h,
and then 50 mL NaOH 1 M was added to it and sonicated for 3 h. Afterwards, HCl
was added to neutralize it and the solution was filtered and then rinsed. Then, 50 mg
of the modified MGO was homogenized in 70 mL of deionized water by
ultrasonication for 10 min. Next, 10 mg of 1-ethyl-3-(3-dimethylaminopropyl)car-
bodiimide and 8 mg of N-hydroxysuccinnimide were added to the latter solution.
This mixture was stirred for 1 h and homogenized by ultrasonication for another
30 min. Then, 2.5 mmol of PEI (MW = 1200) was added into the suspension and
sonicated for 30 min. Finally, the reaction was carried out at 90 °C for 1 h under
stirring. The obtained PEI-MGO was purified by magnetic separation and washed
with deionized water until neutral, and dried under vacuum at 60 °C for 24 h to
achieve PEI-MGO nanosheets.
Preparation of copper supported on polyethylenimine functionalized
magnetic graphene oxide (Cu@PEI-MGO)
To a mixture of PEI-MGO (50 mg) in DMF (10 mL) was added 0.4 mmol of
CuCl2Á2H2O. The mixture was stirred at room temperature for 10 h. The reaction
mixture was filtered and the solid material was washed sequentially with 25 mL of
acetone and then dried in a vacuum oven at 40 °C. Finally, the Cu@PEI-MGO
catalyst was obtained as a dark solid.
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Copper (II)-supported polyethylenimine-functionalized…
General procedure for synthesis of products 3a–j
A mixture of 2-aminobenzamide (1.0 mmol), benzylacetamide (1.0 mmol),
Cu@PEI-MGO (5.0 mg) and NHPI (2.0 mmol) was stirred in acetonitrile (5 mL)
in reflux conditions for 4 h under an oxygen atmosphere. After completion of the
reaction (monitored by TLC), the reaction mixture was cooled, the catalyst was
separated with an external magnet and the product was extracted with ether. The
ether layer was decanted, dried, and concentrated under reduced pressure, and the
semisolid residue was purified by column chromatography on silica gel (eluent:
hexane–EtOAc) affording 3a–j.
Spectral data
2-Phenylquinazolin-4(3H)-one (3a) 1H NMR (DMSO-d6, 500 MHz): d 7.51–7.61
(4H, m), 7.75 (1H, d, J = 8.0 Hz), 7.84 (1H, t, J = 8.0 Hz), 8.16 (1H, d,
J = 8.0 Hz), 8.20 (2H, d, J = 7.0 Hz), 12.50 (1H, s, NH). 13C NMR (DMSO-d6,
125 MHz): d 120.9, 125.7, 126.4, 127.4, 127.6, 128.4, 131.2, 132.6, 134.4, 148.6,
152.1, 162.1; IR (KBr) (mmax/cm-1): 3314 (NH), 1662 (C=O).
2-(4-Methylphenyl)quinazolin-4(3H)-one (3b) 1H NMR (DMSO-d6, 500 MHz): d
2.39 (3H, s, CH3), 7.35 (2H, d, J = 8.5 Hz), 7.50 (1H, t, J = 8.0 Hz), 7.72 (1H, d,
J = 8.0 Hz), 7.82 (1H, t, J = 8.0 Hz), 8.10 (2H, d, J = 8.5 Hz), 8.14 (1H, d,
J = 8.0 Hz), 12.39 (1H, s, NH). 13C NMR (DMSO-d6, 125 MHz): d 20.8, 120.8,
125.7, 126.2, 127.2, 127.5, 129.0, 129.8, 134.3, 141.3, 148.8, 152.1, 162.1; IR (KBr)
(mmax/cm-1): 3319 (NH), 1658 (C=O).
2-(2-Methoxyphenyl)quinazolin-4(3H)-one (3c) 1H NMR (DMSO-d6, 500 MHz):
d 3.88 (3H, s, OCH3), 7.08 (1H, t, J = 7.0 Hz), 7.19 (1H, d, J = 8.5 Hz), 7.50–7.55
(2H, m), 7.70 (1H, d, J = 8.0 Hz), 7.49 (1H, d, J = 7.5 Hz), 7.82 (1H, t,
J = 7.5 Hz), 8.16 (1H, d, J = 7.5 Hz), 12.00 (1H, s, NH). 13C NMR (DMSO-d6,
125 MHz): d 55.7, 111.8, 120.3, 120.9, 122.4, 125.6, 126.3, 127.2, 130.3, 132.1,
134.2, 148.9, 152.1, 157.1, 161.0; IR (KBr) (mmax/cm-1): 3323 (NH), 1662 (C=O).
2-(4-Methoxyphenyl)quinazolin-4(3H)-one (3d) 1H NMR (DMSO-d6, 500 MHz):
d 3.85 (3H, s, CH3), 7.08 (2H, d, J = 8.5 Hz), 7.48 (1H, t, J = 7.5 Hz), 7.70 (1H, d,
J = 7.5 Hz), 7.80 (1H, t, J = 7.5 Hz), 8.14 (1H, d, J = 7.5 Hz), 8.20 (2H, d,
J = 8.5 Hz), 12.33 (1H, s, NH). 13C NMR (DMSO-d6, 125 MHz): d 55.3, 113.8,
120.6, 124.7, 125.7, 125.9, 127.1, 129.3, 134.3, 148.8, 151.7, 161.7, 162.2; IR (KBr)
(mmax/cm-1): 3312 (NH), 1668 (C=O).
2-(Thiophen-2-yl)quinazolin-4(3H)-one (3e) 1H NMR (DMSO-d6, 500 MHz): d
7.24 (1H, t, J = 6.0 Hz), 7.49 (1H, t, J = 8.0 Hz), 7.66 (1H, d, J = 8.0 Hz), 7.80
(1H, t, J = 8.0 Hz), 7.86 (1H, d, J = 6.0 Hz), 8.13 (1H, d, J = 8.0 Hz), 8.23 (1H, d,
J = 6.0 Hz), 12.62 (1H, s, NH). 13C NMR (DMSO-d6, 125 MHz): d 120.8, 125,
126.1, 126.8, 128.3, 129.2, 131.9, 134.5, 137.2, 147.7, 148.5, 161.6; IR (KBr) (mmax
/
cm-1): 3316 (NH), 1664 (C=O).
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M. H. Sayahi et al.
2-(4-Fluoropheny)quinazolin-4(3H)-one (3f) 1H NMR (DMSO-d6, 500 MHz): d
7.38 (2H, t, J = 9.0 Hz), 7.52 (1H, t, J = 7.5 Hz), 7.73 (1H, d, J = 7.5 Hz), 7.83
(1H, t, J = 7.5 Hz), 8.15 (1H, d, J = 7.5 Hz), 8.26 (2H, dd, J = 9.0, 5.5 Hz), 12.53
(1H, s, NH); 13C NMR (DMSO-d6, 125 MHz): d 115.4 (d, 2JC–F = 22.6 Hz), 120.7,
125.7, 126.4, 127.2, 129.1, 130.2 (d, 3JC–F = 8.8 Hz), 134.4, 148.4, 151.3, 162.5 (d,
1JC–F = 104.3 Hz), 164.9; IR (KBr) (mmax/cm-1): 3315 (NH), 1664 (C=O).
2-(2-Chlorophenyl)quinazolin-4(3H)-one (3g) 1H NMR (DMSO-d6, 500 MHz): d
7.50 (1H, t, J = 8.0 Hz), 7.75–7.62 (3H, m,), 7.67 (1H, d, J = 7.5 Hz), 7.71 (1H, d,
J = 8.0 Hz), 7.85 (1H, t, J = 8.0 Hz), 8.19 (1H, d, J = 8.0 Hz), 12.58 (1H, s, NH);
13C NMR (DMSO-d6, 125 MHz): d 121.1, 122.8, 125.7, 126.9, 127.0, 127.3, 129.4,
130.7, 131.4, 133.7, 134.4, 148.5, 152.1, 161.2; IR (KBr) (mmax/cm-1): 3316 (NH),
1657 (C=O).
2-(4-Chlorophenyl)quinazolin-4(3H)-one (3h) 1HNMR (DMSO-d6, 500 MHz): d
7.51 (1H, t, J = 8.0 Hz), 7.60 (2H, d, J = 8.0 Hz), 7.75 (1H, d, J = 8.0 Hz), 7.80
(1H, t, J = 8.0 Hz), 8.16–8.20 (3H, m), 12.63 (1H, s, NH); 13C NMR (DMSO-d6,
125 MHz): d 121.9, 125.2, 126.8, 127.3, 128.5, 129.6, 131.8, 134.6, 136.1, 148.4,
150.3, 163.2; IR (KBr) (mmax/cm-1): 3316 (NH), 1664 (C=O).
2-(3-Nitrophenyl)quinazolin-4(3H)-one (3i) 1H NMR (DMSO-d6, 500 MHz): d
7.57 (1H, t, J = 7.5 Hz), 7.79–7.86 (3H, m), 8.17 (1H, d, J = 7.0 Hz), 8.41 (1H, d,
J = 7.0 Hz), 8.61 (1H, d, J = 7.0 Hz), 9.02 (1H, s), 12.82 (1H, s, NH); 13C NMR
(DMSO-d6, 125 MHz): d 121.2, 122.5, 125.6, 125.7, 126.9, 127.4, 130.1, 133.8,
134.3, 134.5, 147.9, 148.2, 152.2, 162.0; IR (KBr) (mmax/cm-1): 3318 (NH), 1659
(C=O).
2-(4-Nitrophenyl)quinazolin-4(3H)-one (3j) 1H NMR (DMSO-d6, 500 MHz): d
7.50 (1H, t, J = 8.0 Hz), 7.75 (1H, d, J = 8.0 Hz), 7.86 (1H, t, J = 8.0 Hz), 8.16
(1H, d, J = 8.0 Hz), 8.35–8.44 (4H, m), 12.75 (1H, s, NH); 13C NMR (DMSO-d6,
125 MHz): d 120.1, 124.6, 125.7, 128.3, 128.7, 129.2, 135.7, 137.5, 146.3, 146.9,
152.7, 160.2; IR (KBr) (mmax/cm-1): 3314 (NH), 1657 (C=O).
Results and discussion
For the preparation of the Cu@PEI-MGO catalyst, graphene oxide (GO) was first
prepared by the oxidation of purified natural graphite. MGO was constructed by
coprecipitation of Fe2? and Fe3? on the surface of the GO. The obtained MGO was
then functionalized by PEI, which is a nitrogen-rich and water-compatible polymer,
and therefore acts as a ligand for copper, and makes the catalyst water dispersible.
Finally, copper was supported on PEI-MGO to form Cu@PEI-MGO as an efficient
reusable catalyst. The preparation steps are shown in Scheme 2.
The Cu@PEI-MGO catalyst was characterized by different methods. To
determine the Cu content of Cu@PEI-MGO, the inductively coupled plasma
(ICP) technique was used which showed the copper content of the catalyst to be
0.35 mmol/g of the catalyst.
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Copper (II)-supported polyethylenimine-functionalized…
Scheme 2 Preparation steps of Cu@PEI-MGO
Transmission electron microscopy (TEM) and scanning electron microscopy
(SEM) were applied for more characterization of the catalyst (Fig. 2a, b,
respectively). In the TEM image, the presence of magnetic nanoparticles in the
structure of Cu@PEI-MGO can clearly be observed. The magnetic iron oxide
nanoparticles can be seen as dark spots with diameters of about 15 nm in the sheet-
like GO structures. In the SEM image in Fig. 2b, the surface morphology of
Cu@PEI-MGO can be observed.
For more detailed study, Fourier-transform infra-red spectroscopy (FT-IR)
spectroscopy was applied. The FT-IR spectra of GO and Cu@PEI-MGO can be seen
in Fig. 3a, b, respectively. The strong bands at 3428 and 1245 cm-1 in Fig. 3a can
be correlated with the vibrations of the O–H bond. The peaks at 1719 and
1637 cm-1 can be attributed to the vibration of carbonyl bonds in the structure of
GO. In Fig. 3b, in addition to the peaks assigned above, a peak at 576 cm-1 can be
assigned to Fe–O–Fe vibrations. The peak at 3236 cm-1 can be correlated with N–H
vibrations in the structure of the PEI.
As the final characterization step, the thermo-gravimetric analysis (TGA) of
Cu@PEI-MGO was recorded (Fig. 4). According to the diagram, a sharp decrease
from about 300 to 550 °C is attributed to the decomposition of the polyethylenimine
of the catalyst. Fig. S1 shows the x-ray diffraction pattern of the Cu@PEI-MGO
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M. H. Sayahi et al.
Fig. 2 a TEM and b SEM image of Cu@PEI-MGO catalyst
catalyst before and after use. The diffraction peaks confirm the desired structure of
the catalyst.
The magnetic behavior of the catalyst was evaluated by a vibrating-sample
magnetometer (VSM) analysis, and the result is shown in Fig. 5. The superpara-
magnetic behavior of Cu@PEI-MGO can clearly be observed in the VSM curve.
The exact loading of the copper on PEI-MGO is a significant factor. Therefore, ICP
was used for the determination of the copper content in the catalyst. The ICP results
showed that the Cu content is * 0.078 mmol per each gram of Cu@PEI-MGO.
After characterization of Cu@PEI-MGO, the activity of the catalyst was
evaluated in the synthesis of quinazolinones from the reaction of 2-aminobenzamide
and benzylacetamides in the presence of N-hydroxyphthalimide as the oxidizing
agent.
To achieve optimized reaction conditions, the effect of different variables was
investigated for the synthesis of 2-phenylquinazolin-4(3H)-one 3a as the model
system. The effect of various oxidants and solvents was then investigated (Table 1),
which shows that the best yields of the product was obtained with N-
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Copper (II)-supported polyethylenimine-functionalized…
Fig. 3 FT-IR spectra of a GO
and b Cu@PEI-MGO
Fig. 4 TGA diagram of Cu@PEI-MGO
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M. H. Sayahi et al.
Fig. 5 VSM curve of Cu@PEI-
MGO
Table 1 Investigation of the reaction conditions for the synthesis of compound 3a
Entry
Oxidant (mmol)
Catalyst (mol%)
Solvent
Temp. (°C)
Yield (%)a
1
NHPI (1.0)
NHPI (2.0)
NHPI (2.0)
NHPI (3.0)
NHPI (2.0)
NHPI (2.0)
NHPI (3.0)
NHPI (2.0)
NHPI (2.0)
NHPI (2.0)
NHPI (20)
NHPI (2.0)
I2 (2.0)
5
3
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
DMSO
Reflux
Reflux
Reflux
56
62
82
2
3
5
4
5
Room temperature
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
100
31
82
0
5
10
0
6
7
5
76
72
56
NRb
NR
10
66
35
32
24
48
8
5
9
5
DMF
10
11
12
13
14
15
16
17
5
CH2Cl2
5
THF
5
EtOH
5
EtOH
DDQc (2.0)
K2S2O8 (2.0)
H2Od2 (2.0)
TBHPe (2.0)
5
MeOH
5
MeOH
100
5
H2O
100
5
EtOH
100
Reaction condition: 1 (1.0 mmol), 2a (1.0 mmol), solvent (3 mL), 4 h. Bold type (Entry 3) indicates the
best reaction conditions
aIsolated yield
bNR, no reaction
cDDQ = 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone
d30 wt% H2O2 in H2O
eTBHP, tert-butyl hydroperoxide (70 wt% TBHP in H2O)
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Copper (II)-supported polyethylenimine-functionalized…
hydroxyphthalimide (2.0 mmol) as the oxidant and acetonitrile as the reaction
medium in reflux conditions for 4 h (Entry 2). We note that performing the reaction
in the presence of different amounts of Cu@PEI-MGO proved that the product is
obtained in the highest yield when 5 mol% of the catalyst is used. No increase in the
yield was observed with higher catalyst amounts, while in the absence of Cu@PEI-
MGO, no product is formed. This observation proves that the presence of Cu@PEI-
MGO is necessary for the reaction.
To investigate the scope of this reaction, the reaction between 2-aminobenzamide
1 and various benzylacetamide derivatives 2a–j, carrying both electron-donating
and electron-withdrawing substituents, were explored under the optimized condi-
tions to afford the 2-arylquinazolin-4(3H)-ones 3a–j in 62–84% yields (Fig. 6).
A great advantage of Cu@PEI-MGO is its reusability. In order to test the
recycling ability of this catalyst, it was easily separated by an external magnet,
washed with water and ethanol, and used again for the next reaction. The catalyst is
recyclable for 10 consecutive reactions as can be seen in Fig. 7. The reusability
results showed no decrease in catalytic activity. For the recycling study, the catalyst
was isolated via an external magnet after each cycle and washed with ethanol
(3 9 15 mL). Then, the isolated Cu@PEI-MGO was dried, and reused for a
subsequent round of the reaction.
Fig. 6 Investigation of the reaction scope for the synthesis of quinazolin-4(3H)-ones 3a–j
Fig. 7 The reusability of Cu@PEI-MGO after 10 runs
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M. H. Sayahi et al.
O
O
OO
O
PINO
NHPI
N
H
N
H
N
O2
H
(2)
(4)
(5)
NHPI
O
NHPI
NH
N
PINO
(3)
OOH O
N
H
(6)
O
NH
N
H
(10)
PINO
O
OH
O
O
O
O
N
N
H
NH2
H
NH2
PINO
NHPI
(1)
(9)
(8)
(7)
Scheme 3 A proposed mechanism for the preparation reaction of quinazolin-4(3H)-one derivatives
A suggested mechanism can be seen in Scheme 3. In the first step, benzylac-
etamide (2) oxidizes to compound (4) in the presence of quinazolin-4(3H)-ones
(PINO). Compound (4) will form the peroxide compound (6) in two steps, which
convert to (7) in the presence of Cu@PEI-MGO. Compound (7), finally converts to
(9), which reacts with 2-aminobenzaimde (1) and produces compound (10). The
desired compound (3) will be prepared from (10) in the presence of Cu@PEI-MGO
and PINO.
Conclusion
In summary, a novel copper catalyst supported on modified MGO is introduced. The
MGO is functionalized by PEI. The advantage of PEI is the high nitrogen content in
its structure which can be efficiently applied as the ligand for the catalyst. The
hydrophilic nature of PEI makes the catalyst highly water dispersible and therefore
it easily performs the reaction in acetonitrile. The reaction between benzylac-
etamides and 2-aminobenzamide in the presence of Cu@PEI-MGO and NHPI in
acetonitrile provides an efficient approach to the synthesis of 2-aryl quinazolin-
123

Copper (II)-supported polyethylenimine-functionalized…
4(3H)-ones of potential synthetic and pharmacological interest. The simplicity of
the starting materials, the reusability of the catalyst, good yields of the products, and
the use of acetonitrile as a cheap and green solvent are the main advantages of this
method.
Acknowledgements This study was supported by the research council of Tehran University of Medical
Sciences (TUMS), and the Iran National Science Foundation (INSF).
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