A facile one-pot ultrasound assisted for an efficient synthesis of benzo[g]chromenes using Fe3O4/polyethylene glycol (PEG) core/shell nanoparticles

Article abstract of DOI:10.1016/j.ultsonch.2016.04.025

In this research, a general synthetic method for the synthesis of benzo[g]chromenes has been developed using Fe₃O₄/polyethylene glycol (PEG) core/shell nanoparticle under ultrasonic irradiations. Compared to the conventional methods,

Full text of DOI:10.1016/j.ultsonch.2016.04.025

Accepted Manuscript
A facile one-pot ultrasound assisted for an efficient synthesis of benzo[g]chro-
menes using Fe3O4/polyethyleneglycol (PEG) core/shell nanoparticles
Javad Safaei-Ghomi, Fahime Eshteghal, Hossein Shahbazi-Alavi
PII:
S1350-4177(16)30123-7
DOI:
http://dx.doi.org/10.1016/j.ultsonch.2016.04.025
ULTSON 3199
Reference:
Ultrasonics Sonochemistry
To appear in:
Received Date:
Revised Date:
Accepted Date:
4 March 2016
20 April 2016
21 April 2016
Please cite this article as: J. Safaei-Ghomi, F. Eshteghal, H. Shahbazi-Alavi, A facile one-pot ultrasound assisted
for an efficient synthesis of benzo[g]chromenes using Fe3O4/polyethyleneglycol (PEG) core/shell nanoparticles,
Ultrasonics Sonochemistry (2016), doi: http://dx.doi.org/10.1016/j.ultsonch.2016.04.025
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

A facile one-pot ultrasound assisted for an efficient synthesis of
benzo[g]chromenes using Fe3O4/polyethyleneglycol (PEG) core/shell
nanoparticles
Javad Safaei-Ghomi,* Fahime Eshteghal, Hossein Shahbazi-Alavi
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, 51167,
I. R. Iran
Corresponding Author Tel.: +98 31 55912385; fax: +98 31 55552935; *E-mail:
safaei@kashanu.ac.ir
Abstract
In this research, a general synthetic method for the synthesis of benzo[g]chromenes has been
developed using Fe3O4/polyethyleneglycol (PEG) core/shell nanoparticle under ultrasonic
irradiations. Compared to the conventional methods, ultrasound procedure showed several
advantages including mild reaction conditions, high yield products, short reaction times,
reusability of the catalyst and little catalyst loading.
Keywords: Benzo[g]chromenes, Magnetic nanoparticles, PEG core/shell, Fe3O4, Ultrasonic
irradiation, Three-component condensation
1

1. Introduction
Regarding the necessity of obtaining drugs using effective methods to the preparation of organic
compounds, the researchers have carried out many efforts in this area [1]. Ultrasound irradiation
has increasingly been considered as a simple, clean and suitable method in drug synthesis in
recent years [2]. Ultrasound irradiation has been applied to accelerate a number of synthetically
useful reactions through the formation, growth, and implosive collapse of bubbles in a liquid [3].
Bubble collapse initiated by cavitation creates high pressures, intense local heating and very
short lifetimes [4-5]. Compared to conventional heating which provides thermal energy in the
macro system, ultrasound irradiation is able to activate many reactions by providing the
activation energy in micro environment [7-8]. The ultrasound approach offers several
advantages, including higher yields, enhanced organic reaction rates, and milder reaction
conditions, nontoxic, environmentally friendly solvent, waste minimization compared with
traditional methods and saving money, energy and raw materials [9-10]. Recently, ultrasound
irradiation was applied for the appropriate and rapid synthesis of 4H-chromene-3-carbonitrile
scaffolds [11], 2-amino-2-chromenes [12] and 2-amino-4H-chromenes [13]. Chromenes are
attractive targets in organic and medicinal chemistry owing to their potency and wide spectrum
of biological activities including antimicrobial [14], antioxidant [15], antimalarial [16],
antibacterial [17] and anticancer [18]. Among various chromenes, benzo[g]chromenes have
received considerable attention because of their unique biological properties in diverse fields
[19]. The synthesis of benzo[g]chromenes has been reported in the presence of diverse catalysts
including lipase [20], Zn(L-proline)2 [21], DBU [22], Triethylbenzylammonium Chloride
(TEBA) [23], Et3N [24] and 1-butyl-3-methyl imidazolium hydroxide ([bmim]OH) [25].
However, some of the reported methods tolerate disadvantages including long reaction times, use
2

of toxic and non-reusable catalyst and utilize of specific conditions. Therefore, to avoid these
limitations, the exploration of an efficient, easily available catalyst with high catalytic activity
and short reaction time for the preparation of benzo[g]chromenes is still favored. Undoubtedly,
the synthesis of benzo[g]chromenes through multicomponent reactions (MCR) has been paid
much attention because of excellent synthetic efficiency, inherent atom economy, the use of
readily available starting materials, experimental simplicity and environmental friendliness. The
possibility of accomplishing multicomponent reactions with a heterogeneous catalyst under
ultrasonic irradiation could improve their effectiveness from operating cost and ecological points
of view [26-27]. In recent years, core/shell nanoparticles have received considerable attention
because of their unique properties [28-29]. The magnetic core/shell Fe3O4 nanoparticles have
been utilized as a suitable catalyst in many reactions [30, 31]. Therefore, the development of
surface modification of magnetic nanoparticles (MNPs) as important candidates in the search for
supporting of catalysts is currently an issue of increasing interest in chemical reactions. The
surface of MNPs can be functionalized easily through appropriate surface modifications to
enable the loading of a variety of desirable functionalities [32-33]. In the present paper,
Fe3O4/polyethylene glycol (PEG) magnetic composite nanoparticles with a core–shell structure
were prepared. Then, we disclosed a novel methodology for the synthesis of benzo[g]chromenes
by one-pot condensation of aldehydes, malononitrile and 2-hydroxy-1,4-naphthoquinone
catalyzed by core/shell Fe3O4/PEG nanoparticle as a magnetic catalyst under ultrasonic
irradiation.
Scheme 1.
3

2. Experimental
2.1. Materials and Apparatus
All organic materials were purchased commercially from Sigma–Aldrich and Merck and
were used without further purification. A multiwave ultrasonic generator (Sonicator 3200;
Bandelin, MS 73, Germany), equipped with a converter/transducer and titanium oscillator (horn),
12.5 mm in diameter, operating at 20 kHz with a maximum power output of 200 W, was used
for the ultrasonic irradiation. The ultrasonic generator automatically adjusted the power level. All
melting points are uncorrected and were determined in capillary tube on Boetius melting point
microscope. FT-IR measurements were recorded on Magna 550 apparatus using with KBr plates.
The 1H NMR and 13C NMR spectra were recorded on Bruker Avance-400 MHz spectrometers in
the presence of tetramethylsilane as internal standard. The elemental analyses (C. H. N) of the
samples were performed using a LECO CHNS 923 analyser. Nanostructures were characterized
using a Holland Philips Xpert X-ray powder diffraction (XRD) diffractometer (Cu Kα, radiation,
λ = 0.154056 nm), at a scanning speed of 2 °/min from 10 º to 100 ° (2θ). DLS was performed
using a Malvern Zetasizer Nano-S (Malvern Instruments). FE-SEM images of the products were
visualized by a Sigma ZEISS, Oxford Instruments Field Emission Scanning Electron
Microscope. The magnetic properties of nanoparticles have been measured with a vibrating
sample magnetometer (VSM, PPMS-9T) at 300 K in Iran (Kashan University).
2.2. Preparation of Fe3O4/PEG nanoparticles
Fe3O4 nanoparticles were synthesized by FeCl2·4H2O and FeCl3·6H2O according to the reported
procedure [34]. The iron solution was strongly stirred with 100 mL of distilled water, which was
º
heated up to 80 C. The molar ratio of Fe2+ and Fe3+ was 5.5:1. After stirring for 10 min,
4

ammonium hydroxide was added. The precipitates were separated by magnetic decantation with
ethanol and distilled water after cooling of the suspension at room temperature. The subsided
Fe3O4 nanoparticles were dried in a vacuum atmosphere at 60 ºC.
Afterward Fe3O4/PEG magnetic composite nanoparticles with a core/shell structure were
prepared by two step additions of the primary and the secondary surfactants, respectively. In a
250 mL round-bottomed three-necked flask, Fe3O4 nanoparticles (1.0 g) and deionized water (60
mL) were vigorously stirred under a mechanical stirrer, an inlet of nitrogen and a condenser then
mixture was kept under ultrasonic vibration for 20 min. Then a solution of 25 mL oleate sodium
was added under nitrogen protection. The suspension was retaining for 20 min with constant
stirring. The PEG-400 solution was then added to the suspension. Then, the mixture was kept
under ultrasonic vibration for 20 min. The products were purified by magnetic field separation
and decantation with water after cooling of the suspension at room temperature. This purification
procedure was repeated five times. The products were dried under vacuum at 60 ◦C for 10 h.
2.3. General procedure for the preparation of benzo[g] chromenes
A mixture of aldehyde (1 mmol), malononitrile (1.5 mmol), 2-hydroxy-1,4-naphthoquinone (1
mmol) and 12 mg of nano-Fe3O4/PEG in 10 mL of ethanol was sonicated at 60 W power for 15-
20 min. After completion of the reaction, 10 mL of ethanol was added to the mixture and the
catalyst was separated by external magnetic field. The reaction mixture was allowed to cool at
room temperature. After cooling, the crude products were precipitated. The precipitate was
washed with water and cold diethyl ether three times to afford the pure product.
5

2.4. Representative spectral data
2-amino-5,10-dihydro-5,10-dioxo-4-phenyl-4H–benzo[g]chromene-3-carbonitrile (4a):
Orange powder, mp 261-262 °C; IR (KBr) (νmax/cm-1): 3398, 3315, 3177, 2193, 1667, 1592,
1
1406; H NMR (400 MHz, DMSO-d6): δ (ppm) 4.61 (1H, s, CH), 7.29-7.84 (11H, m, Ar and
13
NH2); C NMR (100 MHz, DMSO- d6): δ (ppm) 36.9, 57.9, 119.8, 122.4, 126.2, 126.5, 127.5,
128.1, 129.0, 131.1, 131.4, 134.6, 134.9, 144.0, 149.4, 158.8, 177.3, 183.0; Anal. calcd for
C20H12N2O3: C, 73.16; H, 3.68; N, 8.53; found: C, 73.12; H, 3.61; N, 8.58.
2-amino-4-(4-bromophenyl)-5,10-dihydro-5,10-dioxo-4H–benzo[g]chromene-3-carbonitrile
(4b):
Orange powder, mp 253-255 °C; IR (KBr) (νmax/cm-1): 3396, 3327, 3215, 2188, 1668, 1591,
1
1488. H NMR (400 MHz, DMSO-d6): δ (ppm) 4.62 (1H, s, CH), 7.28-8.04 (10H, m, Ar and
13
NH2). C NMR (100 MHz, DMSO-d6): δ (ppm) 36.5, 57.4, 119.7, 120.7, 121.7, 126.2, 126.5,
130.1, 131.4, 131.5, 131.9, 134.6, 134.9, 143.5, 149.5, 158.7, 177.2, 183.0; Anal. calcd for
C20H11BrN2O3: C, 58.99; H, 2.72; N, 6.88; found: C, 58.94; H, 2.74; N, 6.80.
2-amino-4-(4-chlorophenyl)-5,10-dihydro-5,10-dioxo-4H-benzo[g]chromene-3-carbonitrile
(4c):
Orange powder, mp 249-252 °C; IR (KBr) (νmax/cm-1): 3406, 3333, 3213, 2195, 1668, 1594,
1
1416. H NMR (400 MHz, DMSO-d6): δ (ppm) 4.63 (1H, s, CH), 7.34-8.03 (10H, m, Ar and
13
NH2). C NMR (100 MHz, DMSO-d6): δ (ppm) 36.4, 57.5, 119.7, 121.8, 126.2, 126.5, 128.9,
130.1, 131.1, 131.4, 132.1, 134.6, 134.9, 143.0, 149.5, 158.8, 177.2, 182.9; Anal. calcd for
C20H11ClN2O3: C, 66.22; H, 3.06; N, 7.72; found: C, 66.15; H, 3.09; N, 7.77.
6

2-amino-4-(4-nitrophenyl)-5,10 -dihydro-5,10–dioxo-4H-benzo[g]chromene-3-carbonitrile (4d):
Orange powder, mp 240-242 °C; IR (KBr) (νmax/cm-1): 3456, 3403, 3353, 2185, 1667, 1595,
1
1519. H NMR (400 MHz, DMSO-d6): δ (ppm) 4.75 (1H, s, CH), 7.45-8.15 (10H, m, Ar and
13
NH2). C NMR (100 MHz, DMSO-d6): δ (ppm) 36.4, 56.8, 119.4, 121.1, 124.2, 126.3, 126.5,
129.6, 131.2, 131.4, 134.7, 135.0, 147.0, 149.9, 151.5, 158.8, 177.2, 182.8; Anal. calcd for
C20H11N3O5: C, 64.35; H, 2.97; N, 11.26; found: C, 64.28; H, 2.92; N, 11.21.
2-amino-4-(2-chlorophenyl)-5,10-dihydro-5,10-dioxo-4H-benzo[g]chromene-3-carbonitrile (4e):
Orange powder, mp 237-239 °C; IR (KBr) (νmax/cm-1): 3427, 3320, 3212, 2196, 1662, 1630,
1
1603. H NMR (400 MHz, DMSO-d6): δ (ppm) 5.10 (1H, s, CH), 7.23-8.06 (10H, m, Ar and
13
NH2). C NMR (100 MHz, DMSO-d6): δ (ppm) 33.8, 56.5, 119.3, 121.7, 126.3, 126.5, 128.3,
129.1, 129.8, 130.9, 131.0, 131.3, 132.4, 134.6, 135.5, 141.4, 149.9, 158.8, 177.3, 182.8. Anal.
calcd for C20H11ClN2O3: C, 66.22; H, 3.06; N, 7.22; found: C, 66.26; H, 3.01; N, 7.22.
2-amino-4- (3-nitrophenyl) -5,10-dihydro-5,10-dioxo-4H-benzo[g]chromene-3-carbonitrile (4f):
Orange powder, mp 245-247 °C; IR (KBr) (νmax/cm-1): 3414, 3320, 3186, 2205, 1672, 1585,
1
1532; H NMR (400 MHz, DMSO-d6): δ (ppm) 4.85 (1H, s, CH), 7.48-8.20 (10H, m, Ar and
13
NH2). C NMR (100 MHz, DMSO-d6): δ (ppm) 36.7, 57.1, 119.4, 120.9, 122.6, 122.9, 126.2,
126.5, 130.5, 131.2, 131.4, 134.6, 134.9, 135.3, 146.3, 148.4, 149.8, 158.9, 177.2, 182.8; Anal.
calcd for C20H11N3O5: C, 64.35; H, 2.97; N, 11.26; Found: C, 64.30; H, 2.91; N, 11.22.
7

2-amino-4- (4-Methoxyphenyl) -5, 10 -dihydro-5,10-dioxo-4H-benzo[g]chromene-3-carbonitrile
(4g):
Orange powder, mp 243-245 °C; IR (KBr) (νmax/cm-1): 3443, 3385, 2210, 1744, 1662, 1585,
1456, 1323; 1H NMR (400 MHz, DMSO-d6): δ (ppm) 3.72 (3H, s, OMe), 4.56 (1H, s, CH), 6.84-
13
8.02 (10H, m, Ar and NH2). C NMR (100 MHz, DMSO-d6): δ (ppm) 36.2, 55.4, 58.2, 114.4,
119.9, 122.7, 126.2, 126.5, 129.3, 131.0, 131.5, 134.6, 134.9, 136.1, 149.0, 158.7, 177.4, 182.8.
Anal. calcd for C21H14N2O4: C, 70.39; H, 3.94; N, 7.82; Found: C, 70.47; H, 3.91; N, 7.89.
2-amino-4-(4-Methylphenyl)-5,10-dihydro-5,10-dioxo-4H-benzo[g]chromene-3-carbonitrile
(4h):
Orange powder, mp 242-244 °C; IR (KBr) (νmax/cm-1): 3419, 3311, 3193, 2197, 1668, 1606,
1
1416; H NMR (400 MHz, DMSO-d6): δ (ppm) 2.24 (3H, s, CH3), 4.55 (1H, s, CH), 7.05-8.06
(10H, m, Ar and NH2); 13C NMR (100 MHz, DMSO-d6): δ (ppm) 21.1, 36.5, 57.9, 119.8, 122.5,
126.23, 126.5, 128.0, 129.6, 131.0, 131.5, 134.6.5, 134.9, 136.7, 141.3, 149.2, 158.7, 177.3,
182.8. Anal. calcd for C21H14N2O3: C, 73.68; H, 4.12; N, 8.18; Found: C, 73.76; H, 4.02; N,
8.12.
3. Results and discussion
3.1. Structural analysis of Fe3O4/PEG nanocatalyst
FeCl2·4H2O and FeCl3·6H2O were used as the starting materials for the synthesis of nano-Fe3O4.
In this research, ultrasound irradiation assisted the preparation of Fe3O4/PEG nanoparticles. This
sonication was used to speed dissolution, by breaking the interactions between particles. When
the solution containing precursor is exposed via an ultrasound method, extremely high pressures
8

and temperatures are produced to generate Fe3O4/PEG nuclei. At the beginning of the reaction,
the reactant particles disperse randomly in the water under ultrasounic irradiation. The surface
Fe3O4 modifid by PEG-400, thus the nano Fe3O4/PEG were finally obtained (Scheme 2).
Scheme 2
The particle size diameter (D) of the nano Fe3O4/PEG has been calculated by the Debye–
Scherrer equation (D =Kλ/β cos θ), where β FWHM (full-width at half-maximum or half-width)
is in radian and θ is the position of the maximum of the diffraction peak. K is the so-called shape
factor, which usually takes a value of about 0.9, and λ is the X-ray wavelength. Fig.1 shows the
XRD spectra of nano Fe3O4/PEG. According to the Debye–Scherrer equation, the average
particle sizes of the as-synthesized nano Fe3O4/PEG were calculated and the results show that
nano Fe3O4/PEG was obtained with an average diameter of 8-12 nm.
Fig. 1.
In order to investigate the morphology and particle size of nano-Fe3O4/PEG, FE-SEM image of
nano Fe3O4/PEG was presented in Fig.2. The FE-SEM image shows particles with diameters in
the range of nanometers.
Fig. 2
The FT-IR spectra of the Fe3O4 nanoparticles and core/shell Fe3O4/PEG nanoparticles are shown
in Fig. 3. The peak around 3436cm−1 ascribes to the–OH group. For the Fe3O4 and Fe3O4/PEG
nanoparticles, the peaks at 581.54 cm−1 ascribe to Fe–O group Fig. 3(a) and (b). Two typical
bands near 1413.73cm−1 and 1626.03cm−1 indicated a complex reaction between hydroxy groups
on the surface of Fe3O4 nanoparticles and carboxylate groups of oleate sodium. Absorptions at
9

1143.55cm−1 (–C–O–C–) and 3436cm−1 (the associated hydroxy groups) indicated the existence
of PEG. This result suggested that the Fe3O4 nanoparticles be successfully coated by PEG-400.
[34]
Fig. 3.
TGA of Fe3O4/PEG core/shell MNPs was used in order to confirm the presence of various
groups on the surface of the NPs Fig. 4. The initial weight loss from the catalyst below 190 °C
which could be assigned to the loss of bound water or physically adsorbed solvent. The weight
loss observed at 250–450 °C in TGA curve of nano-Fe3O4/PEG is mainly related to the
decomposition of PEG groups grafted to the Fe3O4 surface.
Fig. 4.
In order to investigate the particle size of nanoparticles, DLS (dynamic light scattering) graph of
the nanoparticles were obtained and are presented in Fig. 5. The DLS graph shows particles with
size in the range of 2-10 nanometers.
Fig. 5.
The magnetic properties of Fe3O4 and Fe3O4/PEG nanoparticles were revealed with the help of a
vibrating sample magnetometer (VSM) (Figure 6). As illustrated in Figure 6, the amounts of
saturation magnetization for Fe3O4 and Fe3O4/PEG are 66.6 emu g-1and 58.25 emu g-1
respectively. These results demonstrate that the magnetization property decreases by coating and
functionalization. However, it is still high enough to be separated by a magnet. These results
prove that the catalysts can be easily separated and recovered by an external magnetic field.
Fig. 6.
10

3.2. Catalytic behaviours of nano-Fe3O4/PEG for the synthesis benzo[g] chromenes
Initially, we focused on systematic evaluation of different catalysts for the model reaction of 4-
nitrobenzaldehyde (1 mmol), malononitrile (1.5 mmol), 2-hydroxy-1,4-naphthoquinone ( 1
mmol) in the different solvents. As illustrated in Table 1, ethanol was preferred as the optimal
solvent. The catalyst showed best activity in ethanol compared to other organic solvents such as
CH3CN, DMF, and H2O (Table1). When the reaction was carried out using nano-Fe3O4/PEG as
the catalyst, the product could be obtained in good yield. The reaction was carried out with
different amounts of nano-Fe3O4/PEG. The results show in Table 1, 12 mg of nano-Fe3O4/PEG
as catalyst was suitable and when the amount of catalyst was increased to 16 mg, the yield was
not improved. The model reaction was carried out in the presence of various catalysts such as p-
TSA, nano- ZnO, SiO2, NiO, SnO, Fe3O4, and nano-Fe3O4/PEG. When the reaction was carried
out using nano-Fe3O4/PEGas the catalyst under ultrasonic irradiation, the product could be
obtained in good yield.
Table 1
In continuation of this method, the role of ultrasonic irradiation and the effect of various powers
of ultrasonic irradiation on the reaction were investigated. These results show that the sonication
certainly affected the reaction system (Table 2). When the reaction was carried out under reflux
conditions, it gave low yields of products and took longer reaction times, while the same reaction
was carried out under ultrasonic irradiation to provide excellent yields of products in short
reaction times. The probable explanation for the positive association of irradiation is that the
ultrasonic irradiation could increase the number of active cavitation bubbles and the size of the
11

individual bubbles, both of which are expected to result in higher maximum collapse temperature
and accelerated respective reaction. We employed various conditions and it was found that the
reaction gave satisfying result in the presence of 12 mg of nano-Fe3O4/PEG under ultrasonic
irradiation with the power of 60W in ethanol.
Table 2.
We examined condensation reaction under ultrasonic irradiation without catalyst. When the
reaction was examined without catalyst, the products were obtained in a moderate to good yields
(Table 1). The results show that the sonication certainly affected the reaction system.
We also applied nano-Fe3O4/PEG in synthesis benzo[g]chromene derivatives from various
aromatic aldehydes under similar condition as represented in Table 3. In general the reactions are
clean and high-yielding. Several groups, such as Cl, Br, NO2, OCH and CH3, are compatible
3
under the reaction conditions. Interestingly, a variety of aromatic aldehydes, including ortho,
meta and para-substituted aryl aldehydes, participated well in this reaction and gave the
corresponding products in a good to excellent yield (Table 3). The influence of electron-
withdrawing and electron-donating substituents on the aromatic ring of aldehydes upon the
reaction yields was investigated. These results show that aromatic aldehydes with electron-
withdrawing groups reacted faster than those with electron-releasing groups.
Table 3.
After completion of the reaction, ethanol was added to the mixture and the catalyst was separated
12

by external magnetic field. Fe3O4/PEG nanoparticles were washed for three to four times with
ethanol and dried at room temperature for 5 h. The separated catalyst can be reused for five
times. As shown in Figure 7, the product yields reduced to a small extent on each reuse (run 1,
95%; run 2, 95%; run 3, 94%; run 4, 94%; run 5, 93%).
Fig. 7.
3.3. The proposed reaction mechanism
A probable mechanism for the reaction using Fe3O4/PEG nanoparticle has been illustrated in
Scheme 3. The formation of product can be rationalized by initial Knoevenagel condensation
reaction between an aldehyde 1 and malononitrile 2; then, the obtained intermediate I has been
attacked by the 2-hydroxynaphthalene- 1,4-dione 3, which leads to the intermediate II on the
active sites of nano-Fe3O4/PEG which are mainly responsible for their catalytic activity, such an
addition intermediate may contribute in a cyclization reaction to generate III; which may
isomerizes under the reaction conditions to produce the fused heterocyclic systems 4a-h. In this
mechanism the nano-Fe3O4/PEG activates the C=O and C≡N groups for better reaction with
nucleophiles. Recently, polyethylene glycol (PEG) was used as a suitable for the synthesis of a
large number of organic transformations [35-40]. Therefore, we used the polyethylene glycol
(PEG) as shell of nano-Fe3O4. This green nanocatalyst could be used for other significant organic
reactions and transformations.
Scheme 3.
13

4. Conclusions
In conclusion, we have developed a simple and highly efficient protocol for the synthesis
ofbenzo[g] chromene heterocyclic systems using nano-Fe3O4/PEG as a magnetic catalyst under
ultrasonic irradiation. The remarkable advantages of this methodology are easy work-up, short
reaction times, recycling of the catalyst, little catalyst loading and use of ultrasonic irradiation as
a valuable and powerful technology.
Acknowledgment
The authors are grateful to University of Kashan for supporting this work by Grant NO:
159196/XXX.
References
1. C. Hulme, V. Gore, Curr. Med. Chem. 10 (2003) 51-80.
2. N.C. Eddingsaas, K.S. Suslick, Nature 444 (2006) 163.
3. K.S. Suslick, Science 247 (1990) 1439–1445.
4. K. S. Suslick, Sci. Am. 260 (1989) 80-86.
5. J. H. Bang, K. S. Suslick, Adv. Mater. 22 (2010) 1039-1059.
6. H. Xu, K. S. Suslick, J. Am. Chem. Soc. 133 (2011) 9148–9151.
7. S. Allahyari, M. Haghighi, A. Ebadi, S. Hosseinzadeh, Ultrason. Sonochem. 21 (2014)
663–673.
8. M. Mirza-Aghayan, N. Ganjbakhsh, M. Molaee Tavana, R. Boukherroub, Ultrason.
Sonochem. 32 (2016) 37–43.
14

9. H. Xu, B. W. Zeiger, K. S. Suslick, Chem. Soc. Rev. 42 (2013)2555-2567.
10. G. Cravotto, P. Cintas, Chem. Soc. Rev. 35 (2006) 180–196.
11. J. Kaur Rajput, P. Arora, G. Kaur, M. Kaur, Ultrason. Sonochem. 26 (2015) 229-240.
12. T. S. Jin, J. C. Xiao, S. J. Wang, T. S. Li, Ultrason. Sonochem. 11 (2004) 393–397.
13. B. Datta, M.A. Pasha, Ultrason. Sonochem. 19 (2012) 725–728.
14. M. M. Khafagy, A.H. F. Abd El-Wahab, F. A. Eid, A. M. El- Agrody, Il Farmaco 57
(2002) 715-722.
15. K. V. Sashidhara, J. N. Rosaiah, G. Bhatia, J.K. Saxena, Eur. J. Med. Chem. 43 (2008)
2592-2596.
16. V. F. De Andrade-Neto, M. O. F. Goulart, J. F. Da Silva Filho, M. J. Da Silva, M. D. C.
F. R. Pinto, A. V. Pinto, M. G. Zalis, L. H. Carvalho, A. U. Krettli, Bioorg. Med.Chem.
Lett. 14 (2004) 1145–1149.
17. S. Kanakaraju, B. Prasanna, S. Basavoju, G. V. P. Chandramouli, J. Molecular Structure.
1017 (2012) 60-64.
18. D. Z. Qiang, J. B. Shi, B. A. Song, X. H. Liu, RSC Adv., 4 (2014) 5607–5617.
19. A. Shaabani, R. Ghadari, A. Sarvary, A. H. Rezayan, J. Org. Chem. 74 (2009) 4372–
4374.
20. F. Yang, H. Wang, L. Jiang, H. Yue, H. Zhang, Z. Wang, L. Wang, RSC Adv. 5 (2015)
5213-5216.
21. B. Maleki, S. Babaee, R. Tayebee, Appl. Organomet. Chem. 29 (2015) 408-411.
22. J.M. Khurana, B.Nand, P. Saluja. Tetrahedron.Lett. 66 (2010) 5637-5641.
23. C. Yao, C. Yu, T. Li, S. Tu, Chin. J. Chem. 27 (2009) 1989-1994.
24. A. Shaabani, R. Ghadari, S. Ghasemi, M. Pedarpour, A. H. Rezayan, A. Sarvary, S. W.
15

Ng, J. Comb. Chem. 11 (2009) 956–959.
25. Y. Yu, H. Gu, X. Li, J. Heterocycl. Chem. 48 (2011) 1264-1268.
26. P. G. Mandhane, R. S. Joshi, D. R. Nagargoje, C. H. Gill, Tetrahedron Lett. 51 (2010)
3138–3140.
27. E. Mosaddegh, Ultrason. Sonochem. 20 (2013) 1436-1441.
28. F. Wang, R. Deng, J. Wang, Q. Wang, Y. Han, H. Zhu, X. Chen, X. Liu, Nat. Mater. 10
(2011) 968-973.
29. S. H. Joo, J. Y. Park, C. K. Tsung, Y. Yamada, P. Yang, G. A. Somorjai, Nat. Mater. 8
(2009) 126-131.
30. Z. Xu, Y. Hou, S. Sun, J. Am. Chem. Soc. 129 (2007) 8698-8699.
31. R. Liu, Y. Guo, G. Odusote, F. Qu, R. D. Priestley, ACS Appl. Mater. Interfaces. 5 (18)
(2013) 9167-9171.
32. J. Safaei-Ghomi, R. Masoomi, M. Hamadanian, S. Naseh, New J. Chem. 40 (2016)
3289-3299.
33. F. Mi, X. Chen, Y. Ma, S. Yin, F. Yuan, H. Zhang, Chem. Commun. 47 (2011) 12804–
12806.
34. D. L. Zhaoa, P. Teng, Y. Xu, Q. Sh. Xia, J. T. Tang, J. Alloys Compd. 502 (2010) 392-
395.
35. M. N. Khan, S. Karamthulla, L. H. Choudhury, M. S. Haque Faizi, RSC Adv. 5 (2015)
22168–22172.
36. V. V. Namboodiri, R. S. Varma, Green Chem. 3 (2001) 146–148.
37. H. Firouzabadi, N. Iranpoor, M. Gholinejad, Adv. Synth. Catal. 352 (2010) 119 – 124.
38. M. Raghu, M. Rajasekhar, B. C. Obula Reddy, C. Suresh Reddy, B. V. Subba Reddy,
16

Tetrahedron Lett. 54 (2013) 3503–3506.
39. M. Veeranarayana Reddy, J. S. Kim, K T. Lim, Y. T. Jeong, Tetrahedron Lett. 55
(2014) 6459–6462.
40. L. Wang, M. Huang, X. Zhu, Y. Wan, Appl. Catal. A: Gen.454 (2013) 160–163.
17

Figure captions
Scheme 1. Synthesis of benzo[g] chromenes using nano-Fe3O4/PEG
Scheme 2. Schematic mechanism for the catalytic activity of nano-Fe3O4/PEG in the synthesis
title compound
Scheme 3. Synthesis of nano-Fe3O4/PEG
Table 1. Optimization of reaction conditions using different catalysts
Table 2. Study of the effect of ultrasonic irradiation on the formation of benzo[g]chromenes
Table 3. Synthesis of benzo[g] chromenes using nano-Fe3O4/PEG under ultrasonic irradiation
Fig 1. XRD patterns of (a) Fe3O4, (b) Fe3O4/PEG nanoparticles
Fig.2. FT-IR spectrum of (a) Fe3O4 (b) Fe3O4/PEG nanoparticles
Fig.3. SEM image of (a) Fe3O4 and (b) Fe3O4/PEG nanoparticles
Fig.4. The TGA graph of Core/shell nano-Fe3O4/PEG
Fig.5. The DLS graph of Core/shell nano-Fe3O4/PEG
Fig.6. Magnetization curves obtained by VSM at room temperature of Fe3O4 and Fe3O4/PEG
Fig. 7. Reusability of nano-Fe3O4/PEG as catalyst for the synthesis of 4d
18

Table 1.Optimization of reaction conditions using different catalystsa
Entry
1
Solvent (condition)
EtOH (reflux)
H2O(reflux)
Catalyst
Time (min)
300
Yieldb(%)
18
p-TSA (5 mol%)
2
nano-ZnO (2 mol%)
nano-SiO2 (3 mol%)
nano-NiO (10 mol%)
nano-SnO (5 mol%)
nano-Fe3O4 (4 mol%)
nano-Fe3O4 (4 mol%)
nano-Fe3O4/PEG (12 mg)
nano-Fe3O4/PEG (12 mg)
nano-Fe3O4/PEG (12 mg)
nano-Fe3O4/PEG (12 mg)
nano-Fe3O4/PEG (8 mg)
nano-Fe3O4/PEG (12 mg)
nano-Fe3O4/PEG (16 mg)
nano-Fe3O4/PEG (12 mg)
nano-Fe3O4/PEG (12 mg)
nano-Fe3O4/PEG (12 mg)
------------
300
21
3
EtOH (reflux)
EtOH (reflux)
EtOH (reflux)
CH3CN (reflux)
EtOH (reflux)
Acetone (reflux)
H2O (reflux)
300
15
4
300
23
5
300
28
6
200
32
7
200
38
8
100
49
9
100
35
10
11
12
13
14
15
16
17
18
19
CH3CN (reflux)
EtOH (reflux)
100
58
80
65
EtOH (US)c
EtOH (US)c
15
15
90
95
EtOH (US)c
CH3CN (US)c
H2O (US)c
15
15
95
82
15
61
DMF (US)c
EtOH (US)c
EtOH (reflux)
15
72
25
43
------------
300
trace
a4-nitro-benzaldehyde (1 mmol), malononitrile (1.5 mmol), 2-hydroxy-1,4-naphthoquinone (1 mmol)
b Isolated yields
c Ultrasonic irradiation (60 W)
19

Table 2.Study of the effect of ultrasonic irradiation on the formation of benzo[g] chromenesa
Entry
Power (W)
Time (min)
Yieldb(%)
1
2
3
4
5
30
40
50
60
70
40
35
25
15
15
51
70
85
95
95
a 4-nitro-benzaldehyde (1 mmol), malononitrile (1.5 mmol), 2-hydroxy-1,4-naphthoquinone (1 mmol) and
nanoFe3O4/PEG (12 mg)
b Isolated yields
20

Table 3. Synthesis of benzo[g] chromenes using nano Fe3O4/PEG under ultrasonic irradiation (60
W)
Entry
Producta
Aldehyde (R)
m.p/°Cref
Time (min)
Yield (%)a
1
H
260-262 23
253-255 24
249-252 24
245-248 23
236-239 24
247-249 24
247-248 24
242-244 24
20
20
20
15
20
15
25
25
85
88
91
95
86
93
80
82
4a
4b
4c
4d
4e
4f
2
4-Br
3
4-Cl
4
4-NO2
2-Cl
5
6
3-NO2
4-OMe
4-Me
7
4g
4h
8
a Isolated yield.
21

CHO
O
O
OH
O
NH2
CN
CN
Fe3O4/PEG
+
+
CN
R
ultrasonic irradiation
EtOH
1
2
3
O
O
4a-h
R
Scheme 1. Synthesis of benzo[g] chromenesusing nano-Fe3O4/PEG
22

OH
OH
OH
HO
PEG
HO
PEG
OH
FeCl3.6H2O
+
PEG
)))))))
NH4OH
HO
Fe3O4 NP
HO
OH
Fe3O4 NP
PEG
OH
N2- 800C
oleate sodium
PEG-400
HO
PEG
OH
PEG
HO
OH
FeCl2.4H2O
PEG
OH
HO
Scheme 2. Synthesis of nano-Fe3O4/PEG
23

Fe3O4
O
PEG
NC
CN
Fe3O4
H
NC
H
CN
OH
H
NC
H2O
NC
H
I
PEG
Fe3O4
O
O
N
O
CN
C
OH
O
H
O
II
PEG
Fe3O4
O
O
NH
CN
O
O
O
NH2
CN
O
H
PEG
III
Fe3O4
Scheme 3. Schematic mechanism for the catalytic activity of nano-Fe3O4/PEG in the synthesis of titled
compound
24

Fig 1. XRD patterns of (a) Fe3O4, (b) Fe3O4/PEG nanoparticles
25

Fig.2. SEM image of (a) Fe3O4 and (b) Fe3O4/PEG nanoparticles
26

Fig. 3. FT-IR spectrum of (a) Fe3O4 (b) Fe3O4/PEG nanoparticles
27

100.0
98.0
96.0
94.0
92.0
90.0
88.0
86.0
84.0
82.0
80.0
78.0
76.0
74.0
25.00
20.00
15.00
10.00
5.00
0.00
-5.00
50.0
100.0
150.0
200.0
250.0
300.0
Temp Cel
350.0
400.0
450.0
500.0
550.0
Fig.4. The TGA graph of Core/shell nano Fe3O4/PEG
28

Fig.5. The DLS graph of Core/shell nano-Fe3O4/PEG
29