One-Pot Synthesis of Benzo[4,5]imidazo[1,2-a]pyrimidin-2-ones Using a Hybrid Catalyst Supported on Magnetic Nanoparticles in Green Solvents

Article abstract of DOI:10.1002/open.202100063

The conversion of soluble polyoxometalate into insoluble polyoxometalate is considered to be one of the major challenges in synthetic organic chemistry. Here, polyoxometalate was bonded to the salt part of an organic branch immobilized on the silica-coate

Full text of DOI:10.1002/open.202100063

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One-Pot Synthesis of Benzo[4,5]imidazo[1,2-a]pyrimidin-2-
ones Using a Hybrid Catalyst Supported on Magnetic
Nanoparticles in Green Solvents
[a]
[b]
Alkassoume Moussa and Abbas Rahmati*
The conversion of soluble polyoxometalate into insoluble
polyoxometalate is considered to be one of the major
challenges in synthetic organic chemistry. Here, polyoxometa-
late was bonded to the salt part of an organic branch
(DMAD), derivatives of benzaldehyde and 2-aminobenzimida-
zole in water/ethanol as a green solvent. 21 derivatives of
benzo[4,5]imidazo[1,2-a]pyrimidin-2-one were synthesized by
this method and fully characterized. The high stability of the
catalyst showed that it can be reused for 6 times without
decreasing in activity. The combination of new synthetic
method, new ferromagnetic heterogeneous nano-catalyst,
green solvent and simple separation method were presented in
this work.
immobilized on the silica-coated Fe O4 nanoparticle and
3
characterized using various techniques. The fabricated complex
was used as a heterogeneous catalyst in a novel one-pot
reaction for synthesis of benzo[4,5]imidazo[1,2-a]pyrimidin-2-
ones using aromatic amines, dimethyl acetylenedicarboxylate
1. Introduction
proceeds in the presence of the lower amount of catalyst by
using this green solvent .
7
A green chemistry approach entails that chemical products and
processes are designed in a way that reduce or eliminate the
use and/or generation hazardous materials from the
The use of heterogeneous catalysts instead of homoge-
neous catalysts has increased in both laboratories and industry
due to easy separation, decreasing of the corrosion, stability
and catalytic activity as well as economic and environmental
[1]
environment. In recent years, the green chemistry (Green
ChemisTREE) has grown and it was converted to an enormous
[8–11]
advantages.
Keggin-type heteropolyacids (HPAs) are homo-
[
2]
tree. Green solvents, heterogeneous catalysts, and one-pot
syntheses are important branches of green chemistry based
approaches.
geneous catalysts which were widely applied in organic
[12,13]
transformations.
The fixation of these soluble heteropolya-
cids on insoluble inorganic-organic hybrid magnetic nano-
particles via covalent bonds not only makes heterogeneous
catalyst but also creates a large contact surface and improves
The utilization of green solvents such as ionic liquids, deep
eutectic solvents, liquid polymers, fluorous solvents, water, and
nontoxic organic solvents such as ethanol has been well
[14,15]
flexibility of branches of HPA.
[3–6]
documented in synthesis of organic compounds.
Water is
Recently, attention to one-pot reactions has increased due
to complex molecules constructed from readily available
starting materials in one-pot without separation of
one of the most important green solvents used for organic
syntheses due to its efficiency, eco-friendly nature, non-toxicity,
low cost, availability, and easy performance as well as its
positive effects on the rate, time and yield of the reaction and
selectivity of organic transformations. Also, the reaction
[16,17]
intermediates.
Multicomponent reactions, a sub group of
one-pot reactions, are divided into three categories entitled
[18]
domino, sequential and consecutive reactions. In consecutive
multicomponent reactions, conditions are changeable and
intermediates are isolable, but no separation takes place due to
[19]
the one-pot nature of the reactions. Thus, these processes are
very important in the economic, environmental and industrial
[
[
a] A. Moussa
Department of Chemistry
University of Isfahan
Isfahan (Iran)
b] Dr. A. Rahmati
Department of Chemistry
University of Isfahan
P. O. Box 81746-73441
Isfahan, (Iran)
[20]
fields and from the viewpoint of the green chemistry. Various
MCRs are applied to synthesize heterocyclic molecules in the
[21,22]
presence and absence of catalysts.
Benzimidazo[1,2-a]pyrimidines are an important category of
N-fused heterocycles containing pyrimidine and benzimidazole
[23]
rings. Benzimidazopyrimidines have also been reported as
E-mail: a.rahmati@sci.ui.ac.ir
[
23–25]
pyrimidobenzimidazoles in literature.
They have widely
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/open.202100063
[26]
[27]
biological properties such as antibacterial,
antiviral,
[28]
[29]
[30]
[31,32]
©
2021 The Authors. Published by Wiley-VCH GmbH. This is an open access
antifungal,
antiulcer,
anti-HIV,
anticancer,
article under the terms of the Creative Commons Attribution Non-Com-
mercial NoDerivs License, which permits use and distribution in any med-
ium, provided the original work is properly cited, the use is non-commercial
and no modifications or adaptations are made.
[33]
[34]
antiproliferative and anti-inflammatory activities. For treat-
ment of Alzheimer disease, some of these compounds have
been applied as allosteric enhancer of acetylcholine affinity at
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[
35]
[51]
muscarinic M receptor, imaging agent for detecting neuro-
to the supported ionic liquid in water very slowly. Immedi-
3
[36]
logical disorders and protection against amyloid β associated
neurotoxicity. They are also used as NK1 receptor antagonist
for treatment of schizophrenia disease. These molecules bind
to DNA via π-π interactions and prohibits replication of DNA
double helix. Moreover, pyrimido[1,2-a]benzimidazole-5(6H)-
ones have been used as potent and orally active inhibitors of
lymphocyte specific kinase.
pyrimidines have been shown antineoplastic activity against
ately, a bulk precipitate was generated and it was washed
several times using water and ethanol until the final catalyst
was obtained. The formation of the catalysts was proved using
various techniques such as EA, FT-IR, SEM, TEM, EDX and VSM.
Initially, elemental analysis techniques such as flame atomic
absorption (FAA), inductively coupled plasma-optical emission
spectrometry (ICP-OES), and CHNS elemental analysis method
were used to prove the structures of the nanomagnetic
compounds (intermediates including NM, NM-SiO2, NM-
SiO @SiPA, NM-SiO @SiPA-MA and NM-SiO @SiPA-MA-Arg) and
[37]
[38]
[39]
[40]
Hydrated benzimidazo[1,2-a]
[41]
some of the human anticancer cell lines. Thus synthesis of
these compounds are very important. A three-component
reaction has been reported by ourselves in 2005.
2
2
2
[42]
In this
final catalyst (NM-SiO @SiPA-MA-Arg@HPA). Table 1, shows the
2
reaction, 4H-pyrimido[2,1-b]benzazoles are synthesized using 2-
aminobenzimidazole, an aldehyde, and a β-ketoester in the
presence of 1,1,3,3-N,N,N’,N’-tetramethylguanidinium trifluoroa-
cetate as an ionic liquid (Scheme 1). This approach has been
developed by other groups using various catalysts and
elemental percentage in the structures in every stage by various
techniques. Results confirm that all layers were successively
immobilized. Also, results show that the amount of iron
percentage decreased at every stage by addition of the layers
(Entries 1 and 5, Table 1). Also, EA revealed that wt% of the C
and N atoms are 2.54 and 1.05% in the structure of the
catalysts. Correspondingly, analyses with AA revealed that wt%
of the Fe, W, Zn, and P atoms are 14.50, 40.41, 1.42, and 1.20%
in the structure of the catalyst, respectively. These results are
almost confirmed by ICP-OES technique. Some water molecules
exist in the surface or cavities of intermediates in form of
chemisorbed and/or physisorbed, to eliminate these physi-
sorbed water molecules and also to decrease the calculation
[43–50]
conditions.
In the rest of these works, we report a new
consecutive four-component reaction for the synthesis of 3,4-
dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-2(1H)-ones by succes-
sive addition of aniline, DMAD, benzaldehyde derivatives and 2-
aminobenzimidazole in the presence of new organic-inorganic
hybrid nanomagnetic catalyst in water/EtOH as a green solvent.
error, the sample is heated at 120–150
°
C for 5 hours, before
2
. Results and Discussion
using in every stage. Next, they were cooled down to room
temperatures while it was fully controlled. These results confirm
the successful bonding of these molecules to previous immobi-
lized molecules. Results showed that the amount of phosphorus
is higher than the actual amount. Probably, some phosphate
ions are adsorbed to silica surface physically.
2
.1. Synthesis and Characterization of NM-SiO @SiPA-MA-Arg
2
@
HPA Catalyst
NM-SiO @SiPA-MA-Arg@)HPA, as a nanomagnetic organic-inor-
ganic hybrid catalyst, was prepared as depicted in Scheme 2.
Initially, Fe O magnetic nanoparticles (MNPs) were fabricated
2
Synthesis steps of the intermediates and NM-SiO @SiPA-MA-
3
4
2
by aqueous co-precipitation manner using FeCl .4H O and
Arg@HPA were also confirmed by the FT-IR spectra. The
spectrum of Fe O (NM) showed two characteristic absorptions
2
2
FeCl .6H O compounds. Then, the surface of nanomagnet was
3
2
3
4
À 1
coated by silica, after that triethoxysilylpropyl amine was
immobilized onto the surface of afforded coated-MNPs. These
inorganic-organic nanomagnetic particles reacted with maleic
anhydride and then with arginine and resulted in the formation
at 632 and 558 cm due to the Fe-O-Fe vibrations. After
coating with a layer of SiO , the FT-IR spectrum of Fe O @SiO
2
2
3
4
(NM-SiO ) proved the addition of another peak at 1059. The
2
presence of the broad absorption signals around 3431 or 3392
indicates OÀ H stretching vibrations representing a strong
intermolecular hydrogen bond in both cases. The presence of
of a supported compound NM-SiO @SiPA-MA-Arg. On the other
2
hand, a solution of heteropoly acid-containing zinc atom was
produced using the reported method in literature from
Na HPO , Na WO .2H O and Zn(II) nitrate salt in water in the
À 1
SiPA was demonstrated by the absorption peak at 2924 cm
related to the stretching vibrations of CH bonds. Also, the
2
4
2
4
2
2
À 1
presence of HNO at pH of 4.8. Finally, this solution was added
broad band at 1049 cm is due to Si-O-C and C-N vibrations
3
Scheme 1. One-pot synthesis of 3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-2(1H)-ones.
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2
Scheme 2. Synthesis of the NM-SiO @SiPA-MA-Arg@)HPA catalyst.
which have overlapped. Peaks at 1704, 1604 and another peak
at 1439 cm correspond to stretching vibrations of C=O, C=C
W=O and WÀ OÀ W bands of the terminal oxygen of polyox-
À 1
[52,53]
ometalate moiety, respectively.
The latter signal has over-
and NÀ CO groups showed the addition of maleic anhydride on
lapped with strong stretching frequencies of CH . These bands
2
NM-SiO @SiPA. The FT-IR spectrum of NM-SiO @SiPA-MA-Arg
demonstrate the construction of the final catalyst. (Figure 1)
The immobilization of the organic part and HPA onto the
Fe O magnetic nanoparticle was confirmed by EDX spectrum
2
2
À 1
showed the bands at about 2750–350 and 1650 cm assigned
to the stretching of the carboxylic acid and guanidine part of
arginine. Based on the literature, the observed stretching
3
4
(Figure 2). This spectrum revealed the presence of the O, C, N,
Zn, Fe, Si, P and W elements in the structure of the catalyst. EDX
À 1
frequencies at 891, 951 and 1079 cm are attributed to PÀ O,
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Table 1. Determination of element wt% in intermediates and catalyst by various methods.
Entry
Technique
FAA
Portion
NM
NM-SiO2
NM-SiO2@SiPA
NM-SiO2@SiPA-MA
NM-SiO2@SiPA-MA-Arg
NM-SiO2@SiPA-MA-Arg @HPA
1
2
3
4
5
6
7
8
9
Fe %
W %
Zn %
P %
Fe %
Si %
W %
Zn %
P %
69.80%
–
–
–
71.04%
–
–
–
39.92%
–
–
–
38.87%
16.34%
–
–
36.22%
–
–
–
35.36%
17.19%
–
–
–
33.65%
–
–
–
32.98%
16.81%
–
–
–
31.40%
–
–
–
31.59%
16.23%
–
–
–
14.50%
40.41%
1.42%
1.20%
13.91%
7.21%
41.07%
1.29%
1.14%
2.54%
0.98%
1.05%
ICP-OES
CHNS
–
–
–
–
1
1
1
0
1
2
C %
H %
N %
2.17%
1.41%
0.84%
4.29%
1.64%
0.84%
6.27%
2.05%
2.41%
0.44%
–
1.19%
–
mapping analysis of NM-SiO @SiPA-MA-Arg@HPA catalyst
2
showed the spatial distribution of the different atoms taken one
by one in the catalyst and the mixture of all atoms in the
catalyst (Figure 3). The morphology of the catalyst was further
identified by FE-SEM analysis (Figure 4A,B). SEM images showed
that particles of the catalyst are relatively uniform and spherical.
Also, the size of the particles differs almost from 20–30 nm.
Also, TEM images clearly illustrates the structure of the
synthesized catalyst were spherical and nanoscale. The average
particle size confirmed the results of SEM. The TEM images
showed that the core of the nanoparticles is nanomagnet and
the shell of the nanoparticle has been covered using organic
structures (Figure 4C, D).
The magnetism of the catalyst was tested by VSM analysis
(Figure 5). Comparison of the magnetism of the NM, NM-
SiO @SiPA-MA-Arg and NM-SiO @SiPA-MA-Arg@HPA displayed
2
2
a difference of 10 emu/g for NM and NM-SiO @SiPA-MA-Arg
2
and 5 emu/g for NM-SiO @SiPA-MA-Arg and NM-SiO @SiPA-MA-
Figure 1. FT-IR: NM (A), NM-SiO
MA (D), NM-SiO
2
(B), NM-SiO
@SiPA-MA-Arg (E) and NM-SiO
2
@SiPA (C), NM-SiO
2
@SiPA-
2
2
2
2
@SiPA-MA-Arg@)HPA (F).
Arg @HPA. The results indicated that the magnetizations
decreased by addition of the organic layers and HPA on to the
Fe O magnetic nanoparticle. This weak magnetization is due
3
4
2
Figure 2. EDX pattern of NM-SiO @SiPA-MA-Arg@HPA catalyst.
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2
Figure 3. MAP images of spatial distribution of the carbon, nitrogen, oxygen, silicium, phosphorus, iron, zinc, tungsten atoms in NM-SiO @SiPA-MA-Arg@HPA.
2 2
Figure 4. SEM images of NM-SiO @SiPA-MA-Arg@HPA catalyst as magnetic nanoparticle in two different scale(A,B). TEM image of NM-SiO @SiPA-MA-Arg@HPA
core/shell in two different scale (C,D).
the decomposition of organic groups. The last stage shows a
weight loss about 3.56% from 330 to 600°C resulting from the
decomposition of organic spacer grafting to the Fe surface. To
determine the amount, type and distribution of acid sites,
temperature-programmed desorption of ammonia (NH -TPD)
3
technique was used. The applied gas in this process was He
monitored by the FTIR apparatus. Before each NH -TPD experi-
3
ment, the catalyst was degassed using He at 300°C in a flow of
1
0 sccm during 1 hour, and cooled down to 110°C. Next, 65 mg
of the catalyst placed in a U-shaped quartz reactor, followed by
the adsorption of 5% NH /He at 110°C for 30 min. The sample
3
was then purged in a He stream for 30 min at 110°C in order to
remove loosely bond ammonia. Then, the sample was heated
3 4 2
Figure 5. The VSM measurements of Fe O (A), NM-SiO @SiPA-MA-Arg (B),
NM-SiO @SiPA-MA-Arg@HPA (C).
2
again from 110°C to 800°C at a heating rate of 10°C/min in a
flow of He (10 sccm). The curve (Figure 6B) shows three areas
corresponding to three range of temperature. The first small
area (31.92) at 100 to 300°C range is related to the organic
first to a weak fixation of the organic chain. Also to the length
of this chain witch is too long as well as its flexibility decreasing
the obstacle to the magnetic fields.
acids (carboxylic acid groups). The second area (421.18) is
assigned to acidic sites of heteropolyacid about 300–600°C.
Finally, the adsorbed NH at 600 to 800°C range corresponds to
3
Thermal gravimetric analysis (TGA) of the NM-SiO @SiPA-
the strong Lewis acids sites in which created by Zn substituted
HPA and possibly defects in HPA structures.
2
MA-Arg@HPA was investigated to study its thermal decom-
position (Figure 6A). The sample was heated from 40°C to
8
30°C at 10°C/min, and showed three main stages. The first
small weight loss of 1.81% at 150°C is assigned to removal of
physically adsorbed water and surface hydroxyl groups, and the
second weight loss about 4.63% at 330°C is probably due to
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2
Figure 6. The TGA (A) and TPD (B) curve of NM-SiO @SiPA-MA-Arg@HPA.
2
.2. Synthesis of Benzoimidazo[1,2-a]Pyrimidin-2-one with
was increased and completed in the short time (2 h) when the
catalyst was used. Next, 2-aminobenzimidazole was added to
the reaction medium and followed by TLC. It showed that the
reaction was completed at considerable time. It was decided to
optimize systematically the reaction conditions such as the
solvent and temperature as well as catalyst amount.
At first, the model reaction (aniline, DMAD, benzaldehyde
and 2-aminobenzimidazole) was done as consecutive four-
component reaction in several solvents in the presence of NM-
NM-SiO @SiPA-MA-Arg @HPA Catalyst
2
[42]
Based on our previous work, a new reaction was designed for
synthesis of benzoimidazo[1,2-a]pyrimidin-2-one. In this reac-
tion, an enamine-one was synthesized in situ from the reaction
of aromatic amine and dialkyl acetylenedicarboxylate and used
as a CÀ H acid instead of β-ketoester (scheme 3).
The designed multicomponent reaction was studied in
ethanol under reflux condition. After 24 h, in the absence of the
catalyst monitoring of the reaction by the TLC showed that no
SiO @SiPA-MA-Arg@HPA catalyst under reflux conditions (Ta-
2
ble 2). The results showed that the protic solvents are almost
better than the others. Among them the water was the best
solvent. When ethanol as co solvent was added to water the
reaction yield was extremely increased. Thus, mixture of water/
ethanol was chosen as reaction media. Next, the effect of the
temperature was checked on the yield of reaction (Table 2,
Entries 8–11). Results showed that the temperature plays an
important role in this approach. When the reaction was
performed at 25 and 50°C, the reaction yields were moderate. It
product was created. Then, the efficiency of the NM-SiO @SiPA-
2
MA-Arg@HPA catalyst was studied in the proposed reaction.
TLC revealed that some products were generated in this stage.
Separation of products showed that the yield of one of them
was be more than the others (23%). The obtained product was
1
13
characterized by IR, H NMR and C NMR spectra as well as
elemental analysis. It was found that the product is benzo[4,5]
imidazo[1,2-a]pyrimidin-2-one. This result encourages us to do
more investigation about this synthesis. All efforts including to
change solvent and temperature as well as catalyst amount to
improve the yield of the reaction failed in the case of domino
process. For this reason, the reaction was done in form of a
consecutive four-component reaction. Consequently, the reac-
tion of an aniline with DMAD was done without any separation.
This step of reaction was performed very fast. It is important to
note that the reaction between aniline and DMAD is exother-
mic, so DMAD should be added drop by drop at room
temperature. Next, aldehyde was added and followed by TLC.
This step proceeded very hard and was not completed even
after 24 h in the absence of the catalyst. The rate of reaction
was realized that the yield of benzo[4,5]imidazo[1,2-a]
pyrimidin-2-one without catalyst is trace even at mixture of
water/ethanol solvent. When different amounts of the catalyst
were loaded it was indicated the optimum amount is 0.04 g.
Finally, the optimum time for the reaction was 7 h in the
presence of catalyst at 70°C.
In order to extend the above reaction to a library of benzo
[4,5]imidazo[1,2-a]pyrimidin-2-ones, various kinds of aryl alde-
hydes and anilines were subjected under optimum conditions
(Scheme 4). The final products differed only according to the
groups substituted in ortho, meta and para of the aldehyde and
aniline. The reaction was performed both either electron-
withdrawing and electron-donating groups. However, the
reaction was not performed with aliphatic aldehydes and
heterocyclic aldehydes such as n-butanal, n-heptanal, furfural,
thiophene-2-carboxaldehyde and pyridine-4-carboxaldehyde
under the optimized condition. Also, 2-aminobenzothiazole, 2-
aminopyridine, 2-aminopyrimidine was used instead of 2-
aminobenzimidazole, unfortunately the reaction did not pro-
ceed. Moreover, diethyl acetylenedicarboxylates (DEAD) and
methyl propiolate was used instead of DMAD. DEAD acted
exactly like DMAD and produced benzo[4,5]imidazo[1,2-a]
Scheme 3. A four-component reactions.
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[
a]
Table 2. Optimization of one-pot consecutive synthesis of the benzo[4,5]imidazo[1,2-a]pyrimidin-2-one.
Entry
Solvent
Temperature/°C
Catalyst amount/g
Yields/%
0
42 (23)
45
41
29
trace
56
86 (86%)
86
54
42
1
2
3
4
5
6
7
8
9
Ethanol
Ethanol
Methanol
Isopropanol
Acetonitrile
Solvent free
reflux
70
–
[b]
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.03
0.02
0.01
–
reflux
70
70
70
70
70
95
50
25
70
70
70
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
O
[c]
O/EtOH
O/EtOH
O/EtOH
O/EtOH
O/EtOH
O/EtOH
O/EtOH
O/EtOH
1
1
1
1
1
1
0
1
2
3
4
5
55
44
32
trace
70
2
[a] Aniline (0.5 mmol), DMAD (0.5 mmol), benzaldehyde (0.5 mmol), 2-aminobenzimidazole (0.5 mmol), NM-SiO @SiPA-MA-Arg@HPA, 20 h, solvent. [b] One-
pot domino synthesis. [c] 7 h.
pyrimidin-2-ones (Scheme 4). While by methyl propiolate mole-
cule, dimethyl 1-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,6-bis
which has been activated by the catalyst. In result, an α,β-
unsaturated compound 9 is created by elimination of one water
molecule. This α,β-unsaturated compound is activated again by
the catalyst via linking onto the oxygen atoms. Next, the
reaction is followed by Michael addition of 2-aminobenzimida-
zole to this active compound 10, followed by compound 11 is
synthesized and activated by catalyst once again. By intra-
molecular cyclization of compound 11, the compound 12 is
created. Finally, the final product (5) is obtained by elimination
of a methanol molecule and other molecules and/or parts by
(
phenylamino)-1,4-dihydropyridine-3,5-dicarboxylate was ob-
tained (Scheme 5).
The structure of products 5a–n is deduced from their IR, H
1
1
3
NMR and C NMR spectra and by elemental analysis. For
example, the FT-IR spectrum of the 5g indicated the formation
of benzoimidazo[1,2-a]pyrimidin-2-ones. The absorption bands
À 1
around 3311 and 3112 cm are related to amid NÀ H and amine
NÀ H bonds, respectively. The vibrations bands at 2948 and
À 1
[42]
2
874 cm were assigned to the CH part. The broad strong
removing the catalyst using a magnet.
3
À 1
vibration signal at 1680 cm is attributed to the stretching
vibrations of carbonyl groups and bending vibrations of NÀ H
groups. Stretching of the imine and vinyl bonds are at 1626 and
The reusability of NM-SiO @SiPA-MA-Arg@HPA catalyst was
2
investigated up to six times in model reaction under optimized
conditions. After each reaction, the catalyst is separated from
the reaction medium by a magnet and washed with 20 ml of
ethanol, to remove reactants and products adsorbed on the
catalyst. After each time, it was dried in an oven at 100°C for
À 1
2
SP )
3
1
496 cm respectively. CÀ N, C( À O and C À O bonds vibrate
(SP )
1
À 1
separately at 1389, 1228 and 1198 cm . The H NMR of the 5g
product shows two singlets at 2.17 and 3.51 ppm for hydrogens
of benzylic CH group and methoxy (OCH ) group, respectively.
2 h and used again with new substrates under the same
conditions. The results showed that the catalyst can be reused
several times due to the negligible decrease in the yields of the
reactions (86 to 84%) (Figure 7A). The FT-IR spectrum and SEM
images of the catalyst were obtained after six rounds (Figure 7B
and 7C). FT-IR spectrum displayed the same signals in both of
the fresh and final catalysts. Just like that, the SEM images
revealed that the morphology and particle size of the catalyst
have the identical shape before and after using of six times.
Thus, these results show that this inorganic-organic hybrid
catalyst is stable.
3
3
Another singlet is also appeared at 5.91 ppm that is related to
hydrogen of CÀ H group. This CH locates among nitrogen and
two aromatic rings. Aromatic hydrogens are seen at δ=6.98–
7
.28 as multiplet. Finally, two hydrogens amine and amid are
observed as two close singlets at 7.56 and 7.58 ppm, respec-
1
3
tively. On the other hand, C NMR shows the production of
1
13
final compound. H-decoupled C NMR spectrum of 5b shows
the carbons of methyl, methine and methoxy are appeared at
2
0.06, 49.73 and 59.52 ppm, respectively. Aromatic carbons are
observed at 110–136 ppm. Carbonyls of amide and ester
functional groups resonate at 162.81 and 165.58 ppm, respec-
tively. In any case, the number of carbon signals is less than the
number of carbons which was expected due to the overlap of 3. Conclusion
some carbons. Thus, elemental analysis was prepared from the
sample and the results completely confirmed that the exper-
imental value is very similar to theoretical value.
The possible mechanism for the synthesis of benzo[4,5]
imidazo[1,2-a]pyrimidin-2-one has been shown in Scheme 6. At
first, aniline (1a) reacts quickly with DMAD (2) and gives
enamine 8. Then, enamine is condensed with an aldehyde
In summary, we have synthesized a new hybrid nanomagnetic
catalyst that with excellent catalytic potential in the synthesis of
the new benzo[4,5]imidazo[1,2-a]pyrimidin-2-one molecules via
one-pot consecutive four components reaction. The high yields
of products were due to a synergistic effect between high
catalytic performance and hydrophobic effect of water solvent.
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2
Scheme 4. Benzo[4,5]imidazo[1,2-a]pyrimidin-2-one derivatives using NM-SiO @SiPA-MA-Arg@HPA catalyst. Aniline (1 mmol), DMAD (1 mmol), benzaldehyde
derivatives (1 mmol), 2-aminobenzimidazole (1 mmol), water/ethanol (5/1 mL), 70°C.
The presence of a long organic part caused the excellent
dispersion of the catalyst in water solvent and easy flexibility of
the catalyst. Using magnetic nanocatalyst facilitated the iso-
lation and reusability. The use of water as a green solvent,
a stable heterogeneous catalyst and excellent yields of the
products as well as recyclability of the catalyst were the
significant results of this work. Alternatively, production of new
organic compounds with valuable heterocyclic parts including
pyrimidine and imidazole rings is one of the main goals of
sustainable organic chemistry. Therefore, we believe that this
Scheme 5. Synthesis of 1,4-dihydropyridine using methyl propiolate mole-
cule in the presence of NM-SiO
2
@SiPA-MA-Arg@HPA catalyst.
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Scheme 6. Suggested mechanism for the formation of benzo[4,5]imidazo[1,2-a]pyrimidin-2-one.
Preparation of Nanomagnetic Particles Coated by Silica
NM-SiO2)
work opens a new path to green chemistry and organic
synthesis.
(
This silica coated NMs have been synthesized using the Stöber
[55]
method with some modifications. The NM (1 g) was dispersed by
the ultrasonic waves in 50 mL of distilled water at 20 min. Then,
this suspension was added into 140 mL of ethanol, stirring at 40 C.
Next, 5 mL of NH .H O was poured into the obtained mixture. After
Experimental Section
°
3
2
that, 1 mL of TEOS was diluted in ethanol (20 mL) and added drop
wise to this suspension. The resulting suspension was kept stirred
mechanically for 14 h at room temperature. Then, this dispersed
mixture was centrifuged at 6000 rpm for 30 min. The magnetic
Fe O /SiO nanoparticles were collected by a magnet and washed
Synthesis of NM-SiO @SiPA-MA-Arg@HPA as
2
Organic-Inorganic Hybrid Nano-Catalyst
Preparation of Fe O magnetic nanoparticles (NMs)
3
4
3
4
2
with ethanol and deionized water several times.
Fe O nanoparticles (NMs) were prepared according to the reported
3
4
[
54]
procedure in the literature.
hexahydrate (4.6 g, 0.017 mol) and iron (II) chloride (2.2 g,
.011 mol) was subjected in 100 ml of deionized water until the
The mixture of iron (III) chloride
Preparation of Nanomagnet-SiO @silyl Propylamine
0
2
(
NM-SiO @SiPA)
salts were completely dissolved. Then, 10 ml of aqueous ammonia
2
was rapidly mixed in nitrogen atmosphere at 25°C for about
[56]
As described in the literature, NM-SiO @Si-PA was synthesized as
2
3
0 minutes with a mechanical stirrer. The obtained precipitates
follows: NM-SiO (1.50 g) was further diluted with ethanol (200 mL)
2
were removed using a magnet and washed with distilled water
several times.
containing γ-amino propyl-triethoxysilane (13 mmol, 3 mL) under
ultra-sonication in a water bath. The resultant dispersion was
bubbled with argon gas for 30 min, and then heated at 40°C under
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Figure 7. Recyclability of the catalyst (A), The SEM images (B) and FT-IR spectrum (C) after six rounds.
mild mechanical stirring for 24 h. Finally, the APTES-modified Fe O
nanoparticles were collected using a magnet and washed repeat-
edly with ethanol and deionized water. The precipitated products
acid was added until an acidic solution was obtained (pH=4.8).
Thus, a solution of heteropolyacid salt was obtained 51.
3
4
of NM-SiO @SiPA were dried at 30°C under vacuum.
2
Final Synthesis of NM-SiO @SiPA-MA-Arg@HPA Catalyst
2
The last step of the synthesis of NM-SiO @SiPA-MA-Arg@HPA was
2
Preparation of Maleic Acid Functionalized
adding the NM-SiO @SiPA-MA-Arg salt to the beaker containing the
2
Nanomagnet-SiO @silyl Propylamine (NM-SiO @SiPA-MA)
2
2
solution of the heteropolyacid salt. The rapid complexion of these
two synthetic products made it possible to have the magnetic
hybrid catalyst which was isolated using a magnet. Then, the
synthesized catalyst was washed several times with distilled water.
NM-SiO @SiPA (0.2 g) and excess amount of maleic anhydride were
2
added to a test tube which was closed thermally and then placed
in an oven at 100°C for 24 h. The obtained product was washed
three times with ethyl acetate and then dried.
General Procedure for the Preparation of Benzo[4,5]imidazo
[1,2-a]pyrimidin-2-one Derivatives
Preparation of silica coated Fe O nanomagnets@silyl
3
4
propylamine-maleic acid-arginine salt (NM-SiO @SiPA-MA-Arg)
2
DMAD or DEAD (1 mmol) was added to a 25 mL round-bottomed
balloon containing aniline derivative (1 mmol) and water (5 mL)
and stirred for 40 min at room temperature. Then, aromatic
First, 1 mmol of arginine was treated with soda in a solution of
methanol: with a ratio of 2:1. The obtained mixture was poured
into a test tube containing 0.1 g of NM-SiO @SiPA-MA and then
aldehyde (1 mmol) and the NM-SiO @SiPA-MA-Arg@HPA catalyst
2
2
hermetically closed. After 5 hours at 120°C, the obtained product
was washed with distilled water and dried. The dry product was
treated with excess hydrochloric acid converting the amine
functions to ammonium salt, which facilitates complexion with
negatively charged heteropolyacid.
(0.04 g) were added to this mixture and stirred until a precipitate
was appeared. Next, 2-aminobenzimidazole (1 mmol) poured out
into this mixture. Subsequently, 1 mL of ethanol was added until
dissolve the formed precipitate and 2-aminobenzimidazole. Prog-
ress of the reaction was monitored by TLC for 4 h. After completion
of the reaction, mixture of the product and catalyst were filtered,
washed and heated in ethanol. Then, the catalyst was removed by
an external magnet. The pure crystals were obtained by the cooling
of the solution.
Synthesis of Heteropolyacid (HPA)
A mixture of 8.33 mmol of sodium tungstate and 0.76 mmol of
sodium hydrogen phosphate in 20 mL of distilled water was stirred
until completely dissolved, and then the addition of 1 mmol of zinc
nitrate. these three reagents were maintained under vigorous
stirring for one hour at room temperature, then concentrated nitric
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Conflict of Interest
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The authors declare no conflict of interest.
Keywords: Benzimidazopyrimidinone
heteropoly acid · magnetic hybrid catalysts · one-pot reactions
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green solvents
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