Functionalized nanomagnetic graphene by ion liquid containing phosphomolybdic acid for facile and fast synthesis of paracetamol and aspirin

Article abstract of DOI:10.1002/aoc.6413

A nanocomposite has been synthesized by supporting of polyaniline-modified polyoxometalate-paired poly(ionic liquid) on the surface of magnetic graphene and characterized by various techniques. The fabricated nanocomposite was found to be a versatile catalyst for the synthesis of paracetamol and aspirin drugs showing high activity and selectivity. The observed high catalytic activity of the newly synthesized catalyst, in the preparation of these two important drugs, can be attributed to the presence of graphene, which provides high surface area for the supporting of polyaniline–polyoxometalate pair and also to the strong acidity of the solid acid. This catalytic system has several advantages, such as simple experimental process, easy separation of the product, solvent-free condition, efficient isolation, and recovery of the magnetic catalyst as well as high reusability.

Full text of DOI:10.1002/aoc.6413

Received: 18 May 2021
DOI: 10.1002/aoc.6413
Revised: 29 July 2021
Accepted: 3 August 2021
R E S E A R C H A R T I C L E
Functionalized nanomagnetic graphene by ion liquid
containing phosphomolybdic acid for facile and fast
synthesis of paracetamol and aspirin
Elahe Nasiri1
| Feridoon Kooshki1
| Mohammad Kooti1
|
Rezvan Rezaeinasab2
1Department of Chemistry, Shahid
Chamran University of Ahvaz, Ahvaz,
Iran
2Department of Medicinal Chemistry,
School of Pharmacy, Lorestan University
of Medical Sciences, Khorramabad, Iran
A nanocomposite has been synthesized by supporting of polyaniline-modified
polyoxometalate-paired poly(ionic liquid) on the surface of magnetic graphene
and characterized by various techniques. The fabricated nanocomposite was
found to be a versatile catalyst for the synthesis of paracetamol and aspirin
drugs showing high activity and selectivity. The observed high catalytic activity
of the newly synthesized catalyst, in the preparation of these two important
drugs, can be attributed to the presence of graphene, which provides high
surface area for the supporting of polyaniline–polyoxometalate pair and also to
the strong acidity of the solid acid. This catalytic system has several advan-
tages, such as simple experimental process, easy separation of the product,
solvent-free condition, efficient isolation, and recovery of the magnetic catalyst
as well as high reusability.
Correspondence
Mohammad Kooti and Elahe Nasirii,
Department of Chemistry, Shahid
Chamran University of Ahvaz,
Ahvaz, Iran.
Email: m_kooti@scu.ac.ir;
elahe_mahz84@yahoo.com
Funding information
Research Council of Shahid Chamran
University of Ahvaz, Iran, Grant/Award
Number: 1398
K E Y W O R D S
aspirin, ionic liquid, magnetic graphene, nanocatalyst, paracetamol
1 | INTRODUCTION
In this regard, Keggin-type heteropolyacids and other
derivatives have been reported to be efficient catalysts for
Paracetamol and aspirin are produced in massive scales
annually because of their widespread use in medicine as
antipyretic and analgesic drugs. In addition to their use
as drugs, aspirin (acetylsalicylic acid) and paracetamol
(N-(4-hydroxyphenyl)acetamide) are also employed as
precursors for the synthesis of several valuable organic
and pharmaceutical materials. Therefore, the synthesis
methods for paracetamol and aspirin should be highly
efficient, simple, safe, and cost effective to be suitable for
high-scale production.[1–5] Concentrated sulfuric and
phosphoric acids are most frequently used as catalysts for
the preparation of these drugs. However, the mentioned
acids are highly corrosive, and the obtained yield of the
drugs is rather poor.[6–10]
the synthesis of organic compounds. These solid acids
have been used as catalysts either in a free state or
supported on proper substrates. Among the various
heteropolyacids, phosphomolybdic acid (PMoA), as Brøn-
sted acid catalyst, has attracted much attention.[11–20]
On the other hand, polyaniline (PANI), one of the
well-known conductive polymers, is widely used as sup-
port for the designing of various hybrid composites. This
is due to its interesting properties, such as low weight,
ease of synthesis, low cost, flexibility, environmental sta-
bility, and optical and characteristic redox properties.
Therefore, Zhang et al. have supported molybdic acid
(H2MoO4, MoA) on PANI microstructure through its
Mo–OH groups. The obtained MoA–PANI hybrid is of
some interest in biochemical and catalysis research
because the presence of protons in the structure of PANI
Solid inorganic acids are another alternative com-
monly used as catalysts toward various organic reactions.
Appl Organomet Chem. 2021;e6413.
wileyonlinelibrary.com/journal/aoc
© 2021 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.6413

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NASIRI ET AL.
provides acidic sites and the Mo(IV) center exhibits
remarkable coordination chemistry.[21]
Advance DPX 400-MHz spectrometer using TMS as
internal standard. FT-IR spectra were obtained using a
FT BOMEM MB102 spectrophotometer. Powder x-ray
diffraction (PXRD) patterns were taken with a Philips
x-ray diffractometer (model PW1840) over a 2θ range
from 10ꢀ to 80ꢀ using Cu Kα radiation (λ = 1.54056 Å).
The FESEM images were obtained using a Hitachi
Japan S4160 scanning electron microscope, and TEM
images were taken with Philips CM10-HT 100-K
instrument. The magnetic properties of the samples
were studied by vibrating sample magnetometry (VSM)
of Meghnatis Daghigh Kavir Company. The molybde-
num content of the G/MF@PANI-PMoA nanocatalyst
was determined using an ICP-AES instrument
The magnetic nanocatalysts, as heterogeneous cata-
lysts with high surface area and consequently more
catalytic sites, can efficiently interact with the precursors
present in the reaction mixture. They can also be readily
separated from the reaction media and recycled and thus
have the advantages of both heterogeneous and homoge-
neous catalysts. Efficient separation of these types of cata-
lysts is achieved by merely applying an external magnetic
field. Therefore, magnetic nanocatalysts can be consid-
ered as green catalysts and are expected to be superior to
nonmagnetic heterogeneous or homogeneous counter-
parts.22–34
Although several methods have been so far reported
for the synthesis of paracetamol and aspirin, finding
highly efficient and more environmentally friendly
methods for the preparation of these important drugs is
still of great value. Therefore, in this study, we have fabri-
(HORIBA
Jobin
Yvon,
Longjumeau
Cedex,
France). Gas chromatography (GC) experiments were
performed with a Shimadzu GC-16A instrument using
a
2-m column packed with silicone DC-200 or
carbowax 20M.
cated
a magnetic hybrid, composed of magnetic
graphene, PANI, and PMoA, through a straightforward
process. In this procedure, nanoscale graphene plates
were first magnetized by depositing of manganese ferrite
(MF) nanoparticles on their surfaces. This was then
followed by coating of the magnetic graphene plates with
PANI and subsequently functionalizing with PMoA. Each
of the components in the prepared hybrid, designated as
G/MF@PANI-PMoA, has its own advantage. That is,
graphene will provide higher surface area, MF ensures
the magnetic property, and PANI offers means for the
anchoring of PMoA, the Brønsted acid, on the core of
this hybrid. The catalytic activity of this magnetic
nanocomposite was examined for the synthesis of para-
cetamol and aspirin under solvent-free condition. It was
found that the synthesis of these drugs is achieved readily
at mild conditions in the presence of a catalytic amount
of this catalyst. Moreover, due to the magnetic and
heterogeneous characters of this catalyst, it can be easily
recovered from the reaction mixture and reused for
several times.
2.2 | Preparation of G/MF@PANI-PMoA
nanocomposite
Graphene/manganese ferrite (G/MF) nanocomposite
was prepared using the previously reported method.36
A
1.0 g of G/MF was added to 50 ml of aqueous solution
of 0.5 M nitric acid containing 0.1 M aniline and
0.125 M ammonium peroxydisulfate. The reaction mix-
ture was stirred for 2 h at room temperature. The
resulting precipitate, consisted of G/MF and PANI, was
then isolated by applying a magnet to fix it on the wall
of the reaction vessel. The product (G/MF@PANI) was
washed with ethanol twice and dried at 60ꢀC for 2 h in
an oven. In the next step, 1.0 g of the pre-synthesized
G/MF@PANI with 0.5 g of PMoA was introduced into
ethanol/water solution (at the ratio of 5:35) and stirred
at room temperature for 24 h. The resulting black pre-
cipitate (G/MF@PANI-PMoA) was then separated mag-
netically and washed twice with distilled water and
dried at 60ꢀC in an oven for 3 h. The amount of molyb-
denum content in the nanocomposite was measured by
ICP analysis to be 0. 360 mmol/g. The step-by-step
preparation of G/MF@PANI-PMoA nanocatalyst is
shown in Scheme 1.
2 | EXPERIMENTAL
2.1 | Chemicals
Aniline (Sigma-Aldrich) was first distilled under vac-
uum prior to use. PMoA was prepared as reported.35
The final products of the catalytic reactions were char-
acterized by comparison of their physical data, such as
2.3 | Synthesis of paracetamol in the
presence of G/MF@PANI-PMoA
1
FT-IR and H NMR spectra, with those of known sam-
A mixture of 4-hydroxyaniline (1.0 mmol, 0.1 g), acetic
anhydride (2 ml, 1.5 mmol), and G/MF@PANI-PMoA
ples. 1H NMR spectra were recorded on a Bruker

NASIRI ET AL.
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nanocatalyst (0.1 g) was stirred at room temperature
under solvent-free condition (Figure S1). The progress of
the reaction was monitored by TLC technique, and it was
completed in 15 min. The heterogeneous nanocatalyst
was magnetically separated, washed with ethanol, and
dried for reuse in a new reaction. The remaining residue
was then recrystallized in deionized water to give pure
paracetamol with 98% yield (Table 1).
magnetic field, washed with ethanol, and dried to be
ready for reuse in a new reaction. Distilled water was
added to the remained organic phase and placed in an ice
bath. The residual acetic anhydride is converted to acetic
acid and was removed from the reaction media. The crys-
tals of aspirin were separated and dissolved in 48 ml of
ethanol/water solvent, in a ratio of 3:1, at 60ꢀC. The solu-
tion was cooled to room temperature and placed in an ice
bath to reform pure aspirin crystals with 97% yield
(Table 1). Identification of the products in both of these
reactions was achieved by FT-IR and H1NMR spectrome-
try techniques and CHN analysis.
2.4 | Preparation of aspirin catalyzed by
G/MF@PANI-PMoA
A mixture of salicylic acid (1.0 mmol, 0.14 g) and acetic
anhydride (2.5 ml, 3 mmol) with catalytic amount of
G/MF@PANI-PMoA nanocatalyst (0.1 g) was stirred
at room temperature and solvent-free conditions
(Figure S2). The progress of the reaction was continu-
ously monitored by TLC and took only 30 min for the
reaction to be completed. Again, the heterogeneous
nanocatalyst was isolated via applying an external
3 | RESULTS AND DISCUSSION
In order to characterize of the as-prepared four-
component G/MF@PANI-PMoA nanocatalyst and con-
firming its composition, FT-IR spectroscopy and other
techniques were utilized.
3.1 | FT-IR spectroscopy
The FT-IR spectra of G/MF@PANI-PMoA, H3PMo12O40,
and G/MF are depicted in Figure 1. In the FT-IR spec-
trum of G/MF (Figure 1c), two peaks at 463 and
582 cmꢁ1 are observed, which can be assigned to Fe–O
stretching in the octahedral and tetrahedral sites of
MnFe2O4, respectively. The observed peak at 3438 cmꢁ1
region is related to OH stretching vibrations on surface of
MnFe2O4 nanoparticles. Also, the graphitic C=C
stretching band at about 1560 cmꢁ1 is observed. The
peaks belonging to MnFe2O4, with some shift (412 and
524 cmꢁ1), are clearly seen in Figure 1a for
SCHEME 1 Stepwise preparation of G/MF@PANI-PMoA
nanocatalyst
TABLE 1 Synthesis of paracetamol and aspirin catalyzed by G/MF@PANI-PMo
Entry
Starting material
Starting material
Product
Yield (%)
TON
TOF (hꢁ1
)
1
98
376.5
1470
2
97
194
388
Abbreviations: TOF, turnover frequency = the catalytic turnover per unit time; TON, turnover number = number of moles of product formed per mole of Mo
in the catalyst.[35]

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NASIRI ET AL.
polyoxoanion by PANI. In fact, the observed slight shifts
of the FT-IR bands of the supported PMoA can be due to
this interaction. The characteristic peaks at 1582 and
1490 cmꢁ1 in the FT-IR spectrum of PANI are due to the
presence of quinoid and benzenoid rings, respectively, in
the polymer chain. Other observed peaks related to PANI
match well with those reported in the literature for this
conductive polymer.37,38
3.2 | PXRD analysis
The XRD patterns of G/MF and G/MF@PANI-PMoA
compounds are presented in Figure 2. The expected
peaks for MnFe2O4 are seen in the XRD patterns of both
G/MF and G/MF@PANI-PMoA (Figure 2a,b). The dif-
fraction peaks (2θ) of the MnFe2O4 at 30.1ꢀ (2 2 0), 35.2ꢀ
(3 1 1), 43.0ꢀ (4 0 0), 53.1ꢀ (4 2 2), 56.6 (3 3 3), and 62.1ꢀ
(4 4 0) are consistent with the standard PXRD data for
the MnFe2O4 (JCPDS card, file no. 02-7158) with a face-
centered cubic (fcc) structure. This observation confirms
that the spinel cubic structure of the MF is retained in
both of these samples. The intensity of the XRD peaks for
G/MF@PANI-PMoA is somewhat lower than that of
G/MF, which may be due to the interaction of the
immobilized ionic liquid with MF nanoparticles. In addi-
tion to the MF peaks, other peaks are also seen in the
XRD pattern of G/MF@PANI-PMoA, which can be
ascribed to PMoA. The PXRD of G/MF@PANI-PMoA in
Figure 2a shows the characteristic peaks of MnFe2O4, but
the peaks are slightly shifted. The incorporation of PMoA
into the MF lattice might be responsible for the larger lat-
tice constants and d-spacing values. On the basis of
Bragg's law, these shifts can be attributed to the change
in the interplanar spacing in the framework structures.
Also, in the XRD pattern of G/MF@PANI-PMoA
nanocomposite, a broad peak was observed at 2θ less
than 30ꢀ, which can be possibly due to the amorphous
phases of graphene and/or PANI.[39,40]
FIGURE 1 FT-IR spectra of G/MF@PANI-PMoA (a), PMoA
(b), and graphene/MnFe2O4 (c)
G/MF@PANI-PMoA, indicating the presence of this
magnetic spinel ferrite in the nanocomposite.
FT-IR spectrum of the prepared H3PMo12O40
(Figure 1b) in the range of 750–1080 cmꢁ1 showed char-
acteristic vibration bands at 1076, 945, 910, and
780 cmꢁ1. Corresponding to the vibrations of the poly-
oxoanion, the peak at 1076 cmꢁ1 could be attributed to
asymmetric stretch vibration of P–Oa (Oa = oxygen atom
of tetrahedral phosphate). The asymmetric stretch vibra-
tion of Mo=Ot (Ot = terminal oxygen atoms) is observed
at 945 cmꢁ1. The bending vibration of Mo–Ob–Mo
(Ob = bridged oxygen of two tungsten atoms) and Mo–
Oc–Mo (Oc = bridged oxygen at the corners of the Keggin
structure) are observed at 910 and 780 cmꢁ1, respectively.
In the FT-IR spectrum of PMoA (Figure 1b), the peaks
observed at 1630 and 3438 cmꢁ1 regions are related to
OH bending and stretching vibrations in structure of
pure H3PMo12O40.
In the spectrum of the nanocatalyst (Figure 1a),
almost all the peaks of neat H3PMo12O40 (PMoA) are
observed at 1077, 942, 906, and 789 cmꢁ1, indicating that
polyoxoanion species is supported on G/MF@PANI. It
has been reported that the interaction between the
supported H3PMo12O40 and PANI, in these types of
composites, is attributed to chemical adsorption of
3.3 | SEM and TEM analysis
The morphology of the as-synthesized nanocomposite
was studied by SEM and TEM analysis. The SEM images
of the synthesized nanocomposite are depicted in
Figure 3. Graphene-like sheet structure coated with
MnFe2O4 and functionalized with ionic liquid that are
well integrated on the surface of graphene is clearly seen
in Figure 3a,b. Its TEM images are presented in
Figure 3c,d, which clearly shows spherical morphology
with slight aggregation. The images indicate that
ionic liquid attached to magnetic nanoparticles

NASIRI ET AL.
5 of 11
FIGURE 2 PXRD patterns of G/MF@PANI-
PMoA (a), G/MF (b), and neat PMoA (c)
(seen as dark spots) is grafted on the graphene sheets
(seen as bright sheets) with almost uniform distribution.
A particle size distribution diagram and the selected area
electron diffraction (SAED) of the G/MF@PANI-PMoA
were shown in Figure 3e,f. The nanocomposite size distri-
bution in Figure 3e shows an average particle size of 70–
80 nm. It can be seen that the nanoparticles are fairly
uniform in size. The six strong diffraction rings in the
SAED were assigned to the (2 2 0), (3 1 1), (4 0 0), (4 2 2),
(3 3 3), and (4 4 0) reflections of the cubic spinel structure
of magnetite, respectively. This was in good agreement
with the XRD results, indicating that MnFe2O4 particles
have high crystallinity.
3.5 | Thermal analysis
To characterize the thermal stabilities of synthesized
magnetic nanocomposite, its thermal decomposition
behavior was investigated by the TGA (Figure 5). The
experiment was performedꢁu1nder nitrogen atmosphere at
a heating rate of 10ꢀC min in the temperature range of
50–1000ꢀC. On the basis of the TGA, Thermal decompo-
sition of nanocomposites can be divided into two stages.
The TGA curve showed a small weight loss (15%) starting
at 50–317ꢀC that can be attributed to the release of the
water molecules and the first steps of degradation of
PANI chains. A large weight loss of around 53% was
observed at 545ꢀC, which is related to the degradation of
organic framework and also to the degradation of the
H3PMo12O40 molecules. The total weight of volatile mate-
rial in the TGA curve for G/MF@PANI-PMoA is 68%.
3.4 | Magnetic property
The magnetic property of G/MF@PANI-PMoA
nanocomposite was measured at room temperature
using the vibration sample magnetometer (VSM), and the
magnetic hysteresis loops are shown in Figure 4. The
value of saturation magnetization (Ms) for G/MF was
43.53 emu/g and decreased to 8.47 emu/g in the final
G/MF@PANI-PMoA nanocomposite. The decrease of Ms
can be attributed to the presence of nonmagnetic PANI
and PMoA components on the surface of G/MF. In spite
of the marked decrease of Ms, G/MF@PANI-PMoA
composite still has significant magnetic property ensur-
ing its effective recovery and separation from the reaction
mixture by applying an external magnetic field.
3.6 | Evaluation of catalytic activity of
G/MF@PANI-PMoA
In order to evaluate the catalytic activity of
G/MF@PANI-PMoA nanocatalyst, it was examined as
catalyst for the preparation of paracetamol and aspirin.
The characterization of the produced paracetamol and
aspirin samples was achieved by FT-IR, 1HNMR,
and CHN techniques. The FT-IR spectrum of paraceta-
mol shows a peak at 1654 cmꢁ1 related to the amide car-
bonyl stretching. Also, two peaks at 3327 and 3164 cmꢁ1

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NASIRI ET AL.
FIGURE 3 The FESEM images (a,b), TEM (c,d), particle size distribution diagram (e), and SAED of G/MF@PANI-PMoA (f)
are assigned to phenolic OH and N–H stretching, respec-
tively (Figure S3). The synthesized paracetamol sample
was further characterized by 1H NMR spectroscopy using
CDCl3 as solvent. The methyl group protons were
observed at 2.1 ppm. Aromatic protons of paracetamol
appeared in the range of 6.5–7.5 ppm. The proton of the
NH group was observed at 9.4 ppm and the proton
of phenolic OH group at 10.2 ppm (Figure S4). The
obtained results of CHN analysis for paracetamol: anal.
calcd. for C8H9NO2 C: 63.5, H:6.00, N: 9.26; found: C:
63.60, H:6.07, N: 9.35. Melting point: 170ꢀC. The physical,
1HNMR, and FT-IR spectral and CHN analysis data of
the prepared paracetamol were compared with those
reported in the literature.[41–44]

NASIRI ET AL.
7 of 11
FIGURE 4 Hysteresis loops of G/MF (a) and G/MF@PANI-PMoA (b)
FIGURE 5 The TGA thermogram of
G/MF@PANI-PMoA
The newly made nanocatalyst was also used in the
preparation of aspirin from salicylic acid and acetic anhy-
dride. The FT-IR spectrum of the obtained aspirin from
this catalytic system shows two peaks at 1741 and
1691 cmꢁ1, which are related to ester carbonyl and acidic
carbonyl respectively (Figure S5). The structure of the
paracetamol and aspirin can be attributed to the presence
of PMoA, as Brønsted acid, in this nanocomposite. To
further prove this idea, each of MnFe2O4, G/MF, and
neat PMoA were examined separately for the preparation
of paracetamol. As seen in Table 2, neither of MnFe2O4
or G/MF has shown any catalytic effect on this reaction;
whereas PMoA was found to be nearly as effective cata-
lyst as G/MF@PANI-PMoA. However, the difficulty in
recovery and recycling of the pure PMoA limits its appli-
cation as catalyst for these types of reactions.
1
synthesized aspirin was further confirmed by H NMR
study. The protons of methyl group in aspirin appeared
at 2.37 ppm, aromatic protons in are observed in the
range of 7.34–8.12 ppm, and the proton of the acidic OH
group is seen at 10.91 ppm (Figure S6). The obtained
results of CHN analysis: anal. calcd. for C9H8O4 C: 60.00,
H:4.47; found: C: 60.09, H:4.39. Melting point: 135ꢀC.
These results are in agreement with the other previously
reported findings.[45–48]
3.7 | Recycling and reusing of the
catalyst
The efficiency of the as-synthesized G/MF@PANI-
PMoA heterogeneous nanocatalyst in preparation of
Facile recovery is considered as valuable property for any
heterogeneous catalytic system. In order to test the as-

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NASIRI ET AL.
TABLE 2 Stepwise optimization of catalyst for the synthesis of
paracetamol
Time
(min)
Entry
Catalystsa
Yield%
1
2
3
4
5
MnFe3O4
15
-
-
G/MF
15
H3PMo12O40
15
85
73
98
G/MF@PANI-PMoA
G/MF@PANI-PMoA (0.1 g)
15
15
aAmount of catalyst: 0.05 g.
TABLE 3 Reusability of G/MF@PANI-PMoA
Run
Fresh
98
1
2
3
4
Yield (%) (paracetamol)
Yield (%) (aspirin)
98
97
98
96
97
97
97
96
SCHEME 2 The proposed mechanism for the synthesis of
97
paracetamol in the presence of G/MF@PANI-PMoA
fabricated catalyst reusability, aspirin and paracetamol
preparation reactions were performed in the presence of
catalytic amount of G/MF@PANI-PMoA under optimized
reaction conditions. After completion of each reaction, the
catalyst was isolated by applying an external magnetic
force, followed by washing it for two times with ethanol.
After drying the isolated catalyst, it was reused in a new
reaction with fresh substrates. The reusability result of this
catalyst is presented in Table 3, which indicates that the
recovered catalyst could be reused for at least four succes-
sive times with almost the same catalytic activity. The
amount of molybdenum was measured in the recycled
nanocatalyst after four runs by ICP-AES analysis. This
measurement showed that the molybdenum content of the
recycled G/MF@PANI-PMoA, after four runs, was
0.356 mmol/g. This shows the loss of only 1.1% of the Mo
amount in the original catalyst. This finding shows that
leaching of the catalyst in this reaction is not significant,
which indicates high stability of the present magnetic
nanocatalyst. The FT-IR spectrum of the nanocatalyst after
recovery is given in Figure S7 in which no clear change
was observed after using the catalyst for four times. Fur-
thermore, the TEM image of the nanocatalyst after recov-
ery, presented in Figure S8, shows no clear change with
the original sample, which also confirms the stability and
green nature of the examined catalyst.
mechanism can be proposed (see Scheme 2) for this
catalytic system. In the preparation of paracetamol,
first, the reaction starts with the adsorption process of
the reactants to the surface of the catalyst, where the
solitary pair of electrons in the carbonyl oxygen of the
acetic anhydride and nitrogen and hydrogen of
4-hydroxyaniline are activated by interaction to ion liq-
uid on surface of G/MF (Intermediate [I]). Then, the
nitrogen of 4-hydroxyaniline, as nucleophilic group,
attacks the carbon of acetic anhydride (electrophile) to
form
a
protonated
tetrahedral
intermediate
(Intermediate [II]). In the next step, the tetrahedral
intermediate loses an acetic acid molecule and results
in a protonated amide, which is still adsorbed to the
catalyst surface. Thus, with the diffusion of acetic acid
into the reaction medium, the desorption of the pro-
tonated amide is initiated with the transfer of electrons
from catalyst to the oxygen of the carbonyl, thus
breaking
the
bond
and
simultaneously
the
deprotonation of paracetamol and the regeneration of
the catalyst.9
An analogous mechanism, as the one suggested for
the paracetamol preparation, can be also proposed for the
reaction of aspirin preparation (Scheme 3). Again,
the starting precursors initially interact with ion liquid
on surface of the nanocatalyst to give Intermediate (I). In
the second step, the hydroxyl group of salicylic acid, as
nucleophilic group, attacks the carbon of the carbonyl
group of acetic anhydride to form Intermediate (II). The
latter will then give Intermediate (III) through some
rearrangement that finally passes through proton transfer
and some other rearrangements ending to the formation
of aspirin.3
3.8 | Proposed mechanisms for
preparation of paracetamol and aspirin
According to the previous studies and our experiences
regarding these types of reactions, a tentative multistep

NASIRI ET AL.
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SCHEME 3 Proposed mechanism for the
preparation of aspirin in the presence of
G/MF@PANI-PMoA
TABLE 4 Comparison of efficiency of the G/MF@PANI-PMoA in preparation of paracetamol with other catalysts
Entry
Catalyst
Solvent
Temp. ꢀC
RT
Time
10 min
15 h
Yield%
75
Ref.
[8]
1
2
3
4
5
6
EST-PtNP
-
[49]
[10]
[50]
[51]
Ammonium acetate
Al-MCM-41/H3PO4
Zeolite β or heteropolyacid
CF@[Cu2(Si–N=SA)2(2,20-bipy)2 (PTA)]
G/MF@PANI-PMoA
-
220
95
Acetone
70
1 h
81
-
-
-
280–300
RT
15 h
86
1 min
15 min
98
RT
98
This work
3.9 | Comparison of the results of
present work with previously
reported works
hydroquinone reaction with high yield (95%).
Unfortunately, this method has the limitations of high
temperature (220ꢀC) and long reaction time (15 h)
(Table 4, Entry 2).[49]
In Tables 3 and 4, the catalytic activity of the as-prepared
nanocatalyst was compared with other recently studied
catalysts. Although some alternative catalysts have been
so far introduced to improve the process of paracetamol
and aspirin preparation, most of the used catalysts have
their own limitations. One of the main encountered prob-
lems in using these catalysts is the difficulty of their
regeneration and recycling for repeated usage in order to
avoid releasing of hazardous waste into the environment.
Harsh reaction condition is another drawback that most
of the reported catalytic systems for these reactions are
suffered from. The data in Table 4 show that the hetero-
geneous nanocatalyst of the present work is superior to
the previously reported catalysts with respect to reaction
times and reaction conditions.
Another method was used for the synthesis of para-
cetamol by Ghiaci and coworkers. In this reaction, an
environmentally benign synthetic method using Al-
MCM-41 modified with H3PO4 as solid acid catalyst pre-
sents some advantages; however, the use of solvent, the
presence of H3PO4, and the low yield are considered as
drawbacks of this system (Table 4, Entry 3).[10]
On the other hand, for the preparation of aspirin, two
catalysts have been recently reported, which seem to be
promising for improving the acetylation of salicylic acid.
Tyagi et al.[4] have synthesized nanocrystalline sulfated
zirconia solid acid catalyst, which was found to be effi-
cient in minimal amount to give excellent yield of
acetylsalicylic acid crystals from its precursors (Table 5,
Entry 2). However, in spite of some advantages of this
catalytic system, high yield of aspirin can be only
obtained at reaction temperature of 120ꢀC, and the molar
Joncour et al. have recently designed a green
chemical method for direct synthesis of paracetamol from

10 of 11
NASIRI ET AL.
TABLE 5 Comparison of efficiency of the G/MF@PANI-PMoA in preparation of aspirin with other catalysts
Entry
Catalyst
Solvent
Temp. ꢀC
Time(h)
Yield%
80
Ref.
[7]
1
2
3
4
WO3/ZrO2
-
-
-
-
120
90
2
[4]
[2]
Sulfated zirconia
H14[NaP5W30O110
2
95
]
25
5
78
G/MF@PANI-PMoA
RT
30 min
97
This work
ratio of acetic anhydride to salicylic acid has to be higher
than 3. In addition, the catalyst has to be heated at high
temperature (450ꢀC) for regeneration purposes. The other
reported catalyst for this preparation is WO3/ZrO2 solid
super-acid, which was designed by Zhang and coworkers.
The synthesis of this catalyst, however, is rather tedious,
and the obtained yield of acetylsalicylic acid using this
catalyst was less than 80%. Also, the catalyst has to be
calcined at 550ꢀC before reuse in another reaction
(Table 5, Entry 1).[7]
ACKNOWLEDGMENTS
The authors wish to acknowledge the support of this
work (Grant No. 1398) provided by the Research Council
of Shahid Chamran University of Ahvaz, Iran.
DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are avail-
able in the supplementary material of this article.
ORCID
In brief, compared with the previous methods that
had been used for the synthesis of paracetamol and aspi-
rin, the current approach has advantages in terms of
time, cost, and environmental safety. This is because the
reactions were carried out at room temperature, solvent-
free condition, and atmospheric pressure within a very
short period of time, without using complex compounds
or expensive equipment. Moreover, the advantage of our
introduced nanocomposite will be more evident when its
magnetic property is taken into account, which ensures
facile and efficient separation of the nanocatalyst, one of
the crucial steps in the recycling process. Consequently,
according to all the advantages of the present catalytic
system, it might be a potentially suitable method to be
introduced for the preparation of paracetamol and aspirin
drugs, as well as other similar organic compounds, at
large scales.
Elahe Nasiri https://orcid.org/0000-0003-2701-4691
Feridoon Kooshki https://orcid.org/0000-0003-3079-
3470
Mohammad Kooti https://orcid.org/0000-0002-5226-
349X
Rezvan Rezaeinasab https://orcid.org/0000-0002-5638-
3106
REFERENCES
[1] A. Majedi, F. Davar, A. Abbasi, Ind. Eng. Chem. 2014, 20,
4215.
[2] F. F. Bamoharram, M. M. Heravi, M. Roshani, A. Gharib, M.
Jahangir, J. Chin. Chem. Soc. 2007, 54, 1017.
[3] D. Montes, M. Sanabria, J. Garcia, J. Castro, J. Fajardo,
J. Chem. Educ. 2006, 83, 628.
[4] B. Tyagi, M. K. Mishral, R. V. Jasra, J. Mol. Catal. A: Chem.
2010, 317, 41.
[5] S. Jung, Y. Tsukuda, R. Kawashima, T. Ishiki, A. Matsumoto,
A. Nakaniwa, M. Takagi, T. Noguchi, N. Imai, Tetrahedron
Lett. 2013, 54, 5718.
[6] A. Bhattacharya, V. C. Purohit, V. Suarez, R. Tichkule, G.
Parmer, F. Rinald, Tetrahedron Lett. 2006, 47, 1861.
[7] C. Zhang, T. Liu, H. J. Wang, F. Wang, X. Y. Pan, Chem.
Eng. J. 2011, 174, 236.
[8] B. H. San, S. Ravichandran, K. Park, V. K. Subramani, K. K.
Kim, ACS Appl. Mater. Interfaces 2016, 8, 30058.
[9] A. N. Oliveira, E. T. L. Lima, D. T. Oliveira, R. S. Angelica,
E. H. A. Andrade, G. N. R. Filho, C. E. F. Costa, F. F. Costa, R.
Luque, L. A. S. Nascimento, Materials 2019, 12, 2995.
[10] M. Ghiaci, H. Aghaei, M. Oroojeni, B. Aghabarari, V. Rives,
M. A. Vicente, I. Sobrados, J. Sanz, Catal. Commun. 2009, 10,
1486.
[11] A. Shaabani, A. Maleki, Appl. Catal. A: Gen. 2007, 331, 149.
[12] Y. Leng, J. Zhao, P. Jiang, J. Wang, ACS Appl. Mater. Interfaces
2014, 6, 5947.
[13] W. R. K. Thalgaspitiya, T. K. Kapuge, J. He, P. Kerns, A. G.
Meguerdichian, S. L. Suib, Dalton Trans. 2020, 49, 3786.
4 | CONCLUSIONS
In the present work, we described a straightforward
protocol for the synthesis of G/MF@PANI-PMoA, an ion
liquid magnetic nanocomposite catalyst, containing a
mineral acid. We also demonstrated that the prepared
catalyst could be used for a one-pot preparation of
paracetamol and aspirin drugs through a mild, fast, cost-
effective, and environmentally friendly procedure. This
method offers significant advantages compared with the
currently available synthetic processes so far used for the
synthesis of these important drugs. Therefore, the intro-
duced nanocatalyst in this study may be practically used
for large-scale production of various drugs in pharmaceu-
tical industry.

NASIRI ET AL.
11 of 11
[14] M. Kooti, E. Nasiri, J. Mol. Catal. A: Chem. 2015, 406, 168.
[15] D. Zhang, D. Zhang, W. Zhang, Z. Lin, J. Dong, N. Zhen, Y.
Chi, C. Hu, Inorg. Chem. 2020, 59, 9756.
[16] S. H. Mansourian, S. Shahhosseini, A. Maleki, Russ. J. Appl.
Chem. 2019, 92, 1291.
[36] M. Kooti, P. Kharazi, H. Motamedi, J. Taiwan Inst. Chem. Eng.
2014, 45, 2698.
[37] M. Ghorbanloo, H. Hosseini Monfared, C. Janiak, J. Mol.
Catal. A: Chem. 2011, 345, 12.
[38] L. Lu, Y. Xie, New J. Chem. 2017, 41, 335.
[17] M. Lei, Q. Gao, K. Zhou, P. Gogoi, J. Liu, J. Wang, H. Song, S.
Wang, X. Liu, Sep. Purif. Technol. 2021, 257, 117933.
[18] W. Xie, F. Wan, Chem. Engin. J. 2019, 365, 40.
[19] S. Saikia, R. Borah, Appl. Organomet. 2020, 34, 1.
[20] M. A. Rezvani, M. H. Seyed, A. Mirsadri, Appl. Organomet.
2020, 34, 1.
[21] L. Zhang, L. Zhang, M. Wana, Eur. Polym. J. 2008, 44, 2040.
[22] S. Zhang, P. He, W. Lei, G. Zhang, J. Electroanal. Chem. 2014,
724, 29.
[39] Z. Cui, C. X. Guoa, C. M. Li, J. Mater. Chem. A, J. Mater. Chem.
A 2013, 1, 6687.
[40] J. Tao, Appl. Mech. Mater. 2014, 484-485, 137.
[41] M. L. Peterson, D. McIlroy, P. Shaw, J. P. Mustonen, M.
Oliveira, O. Almarsson, Cryst. Growth des. 2003, 3, 761.
[42] M. A. Neumann, M. A. Perrin, CrystEngComm 2009, 11, 2475.
[43] V. K. Pecharsky, P. Y. Zavalij, Fundamentals of Powder Diffrac-
tion and Structural Characterization of Materials, Springer,
Maryland, USA 2009.
[23] Z. Cui, C. X. Guo, C. M. Li, J. Mater. Chem. A 2013, 1, 6687.
[24] S. Ren, M. Xu, Y. Yang, S. Ma, C. Hao, J. Appl. Polym. Sci.
2014, 131, 41033.
[25] J. Gao, T. Yang, X. Wang, Q. He, P. He, L. Jia, L. Du, H. Deng,
H. Zhang, B. Jia, X. He, B. Tang, Microchem. J. 2020, 158,
105158.
[44] M. A. Perrin, M. A. Neumann, H. Elmaleh, L. Zaske, Chem.
Commun. 2009, 14, 3181.
[45] J. Olmsted III, J. Chem. Educ. 1998, 75, 1261.
[46] S. G. Zhang, Fine Organic Chemicals Technique Handbook,
China Machine Press, Beijing, China 1991.
[47] C. Ouvrard, S. L. Price, Cryst. Growth des. 2004, 4, 1119.
[48] X. Yan, H. He, J. Meng, C. Zhang, M. Hong, X. Tang, Drug
Dev. Ind. Pharm. 2012, 38, 1221.
[26] P. R. A. Selvan, E. Subramanian, R. Murugesan, J. Appl. Chem.
2017, 13, 593.
[27] G. G. Papagianni, D. V. Stergiou, G. S. Armatas, M. G.
Kanatzidis, M. I. Prodromidis, Sens. Actuators B Chem. 2012,
173, 346.
[28] L. C. P. Almeida, A. D. Gonçalves, J. E. Benedetti, P. C. M. L.
Miranda, L. C. Passoni, A. F. Nogueira, J. Mater. Sci. 2010, 45,
5054.
[49] R. Joncour, N. Duguet, E. Metay, A. Ferreira, M. Lemaire,
Green Chem. 2014, 16, 2997.
[50] S. Gopinathan, C. Gopinathan, J. Kuruvilla, S. Pardhy, A.
Ratnasamy, U.S. Patent 5856575, 1999.
[51] M. Kooti, E. Nasiri, Appl. Organomet. Chem. 2018, 32, 1.
[29] S. R. Thakare, V. R. Mate, K. Urkude, S. B. Gawande,
FlatChem 2020, 22, 100179.
SUPPORTING INFORMATION
Additional supporting information may be found in the
online version of the article at the publisher's website.
[30] R. G. Rani, S. Kumar, Int. J. Hydrogen Energy 2019, 44, 16933.
[31] A. Maleki, Z. Varzi, F. Hassanzadeh, Polyhedron 2019,
171, 193.
[32] A. Maleki, H. Movahed, P. Ravaghi, Carbohydr. Polym. 2017,
156, 259.
[33] A. Maleki, P. Zand, Z. Mohseni, RSC Adv. 2016, 6, 110928.
[34] A. Maleki, M. Azizi, Z. Emdadi, Green Chem. Lett. Rev. 2018,
11, 573.
How to cite this article: E. Nasiri, F. Kooshki,
M. Kooti, R. Rezaeinasab, Appl Organomet Chem
2021, e6413. https://doi.org/10.1002/aoc.6413
[35] J. C. Bailar, H. S. Booth, M. Grennert, Inorg. Synth. 1939,
1, 132.