Magnetic cobalt ferrite nanoparticles functionalized with citric acid as a green nanocatalyst for one-pot three-component sonochemical synthesis of substituted 3-pyrrolin-2-ones

Article abstract of DOI:10.1007/s11164-019-03878-1

Abstract: A clean, convenient and facile approach for one-pot ultrasonic assisted synthesis of substituted 3-pyrrolin-2-ones from diethyl acetylenedicarboxylate, aniline and aldehyde derivatives is described. The reactions were carried out in the presence

Full text of DOI:10.1007/s11164-019-03878-1

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03878-1
Magnetic cobalt ferrite nanoparticles functionalized
with citric acid as a green nanocatalyst for one‑pot
three‑component sonochemical synthesis of substituted
3‑pyrrolin‑2‑ones
Hamideh Ahankar1 · Ali Ramazani1,2 · Katarzyna Ślepokura3 · Tadeusz Lis3 ·
Vasyl Kinzhybalo4
Received: 22 March 2019 / Accepted: 3 June 2019
© Springer Nature B.V. 2019
Abstract
A clean, convenient and facile approach for one-pot ultrasonic assisted synthesis of
substituted 3-pyrrolin-2-ones from diethyl acetylenedicarboxylate, aniline and alde-
hyde derivatives is described. The reactions were carried out in the presence of an
efcient, green and reusable acidic nanocatalyst, magnetic cobalt ferrite nanopar-
ticles functionalized with citric acid (CoFe2O4@CA), with high yields under mild
conditions. Also, use of ultrasound irradiation made this approach an attractive pro-
tocol for the synthesis of these products. The method has been successful in achiev-
ing the green chemistry objective. An energy efcient protocol using ultrasound
irradiation instead of conventional heating or stirring and use of ethanol as a non-
hazardous, inexpensive and green solvent in the one-step reaction against sequen-
tial reaction steps thus combining the features of both economic and environmental
advantages.
Graphic abstract
In this research, magnetic cobalt ferrite nanoparticles functionalized with citric
acid (CoFe2O4@CA) catalyzed synthesis of substituted 3-pyrrolin-2-ones under
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-03878-1) contains supplementary material, which is available to authorized users.
*
Ali Ramazani
aliramazani@znu.ac.ir; aliramazani@gmail.com
1
2
Department of Chemistry, University of Zanjan, P O Box 45195-313, Zanjan, Iran
Research Institute of Modern Biological Techniques, University of Zanjan, P O Box 45195-313,
Zanjan, Iran
3
4
Faculty of Chemistry, University of Wrocław, 14 Joliot-Curie St., 50-383 Wrocław, Poland
Institute of Low Temperature and Structure Research, Polish Academy of Sciences, P O
Box 1410, 50-950 Wrocław, Poland
Vol.:(0123456789)
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H. Ahankar et al.
ultrasonic irradiation via a practical and environmentally benign one-pot three-com-
ponent protocol.
Keywords Ultrasonic irradiation · Acidic nanocatalyst · Magnetic cobalt ferrite ·
3-Pyrrolin-2-ones
Introduction
Nowadays, the implementation of the principles of green chemistry in chemi-
cal reactions, especially multicomponent reactions (MCRs) in green solvents has
attracted the attention of many chemists and researchers. In fact, this has become
one of the main goals of research and industrial centers [1–3].
This phenomenon is not only due to the abundance and the low cost of green
solvents, but also because of their unique properties in chemical reactions with
higher efciency and selectivity, as compared to other organic solvents. Given
the growing importance of preserving the environment and the development
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Magnetic cobalt ferrite nanoparticles functionalized with…
of sustainable or green chemistry, it is expected that by these eforts, new and
efcient methods will be developed to obtain a wide range of compounds using
green solvents in MCRs [4, 5].
In recent years, the synthesis and usage of nanoparticles, especially magnetic
nanoparticles of various ferrites, have gained remarkable attention in chemical
reactions as a green and reusable catalyst. The active sites, small size, and the
high surface area of magnetic nanoparticles contribute to their very good cata-
lytic activity. It should be noted; these nanoparticles have some outstanding ben-
efts; for example, they are inexpensive, non-toxic, recyclable, reusable, easily
available and environmentally benign [6–10]. Although, there are some refer-
ences regarding the catalytic properties of magnetic cobalt ferrite nanoparticles
(CoFe2O4 MNPs) grafted or coated of these nanoparticles with diferent organic
ligands like silica, dendrimers, surfactants, polymers, biomolecules, metal or
nonmetal elementary substances in MCRs [11–14], oxidation reactions [15, 16]
and biomedical researches [17–19], but the magnetic nanoparticles of CoFe2O4
functionalized with citric acid have not been investigated in MCRs.
In recent decades, scientists are seeking to produce diverse heterocyclic com-
pounds with important medicinal, therapeutic and biological properties using
MCRs in green solvents to develop a sustainable environment. Pyrrolidinone
derivatives such as (-)-rolipram [20], piracetam [21], (S)-(-)-cotinine [22], etho-
suximide [23], doxapram [24] and povidone [25] are signifcant heterocyclic
compounds as drugs involving 2-pyrrolidinone moiety with medicinal and bio-
logical attributes. Also, some important natural products have been reported to
contain a 2-pyrrolidinone ring such as salinosporamide A [26], lactacystin [27],
and (-)-azaspirine [28]. In addition, two important compounds of this category,
N-Methyl-2-pyrrolidone (NMP) and N-Vinylpyrrolidone (NVP), have pharma-
ceutical and industrial applications and are produced industrially [29]. Moreo-
ver, there are several reports showing that many natural and synthetic compounds
have considerable biological and medicinal properties; these include HIV-1 inte-
grase inhibitors, antitumor, anticancer, antibacterial, antiinfammatory, and anti-
microbial [30–35].
As part of our ongoing program aiming to synthesise substituted 3-pyrrolin-
2-ones, once again we report a green, clean and new method for the synthesis
of substituted 3-pyrrolin-2-ones as a heteroatom-containing organic compound in
the presence of magnetic cobalt ferrite nanoparticles functionalized with citric
acid (CoFe2O4@CA) under the ultrasound irradiation in the ethanol solvent. We
used a green catalyst, solvent and energy for the one-pot sonochemical synthe-
sis of substituted 3-pyrrolin-2-ones without generating harmful by-products from
aniline, diethyl acetylenedicarboxylate and aldehyde derivatives. We found that
no reference has been reported for the production of the desired compounds in the
presence of green solvents, magnetic nanoparticles ferrites, and the use of ultra-
sonic waves. Herein, we explain an easy and efectual sonochemical synthesis of
several substituted 3-pyrrolin-2-ones from aniline (1), diethyl acetylenedicarbox-
ylate (2) and aldehydes (3a–p) in the presence of CoFe2O4@CA under ultrasonic
irradiation (Scheme 1).
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H. Ahankar et al.
Scheme 1 Ultrasonic-assisted synthesis of substituted 3-pyrrolin-2-ones
Experimental
Materials and methods
All reagents and solvents were purchased from commercial sources such as Merck,
Fluka, and Aldrich. The structural properties of CoFe2O4@CA were characterized
by X-ray powder difraction (XRPD) with an X’Pert-PRO advanced difractometer
using Cu (Kα) radiation (wavelength: 1.5406 Å), operated at 40 kV and 40 mA at
room temperature in the range of 2θ from 20° to 80°. The particle size and morphol-
ogy of the surfaces of the sample were analyzed by scanning electron microscopy
(KYKY Co., China, Model: EM 3200). The disc was coated with gold in an ioniza-
tion chamber. The thermogravimetric analysis (TGA) was carried out using a Set-
aram-SETSYS-16/18 thermogravimetric analyzer, operated under air atmosphere,
with a heating rate of 10 °C/min and in the range of 30–800 °C.
Sonication was performed in a Bandelin SONOPULS ultrasonic homogenizer
(made in Germany) with 20 kHz processing frequency, a nominal power of 250 W
and uniform sonic waves. Reactions were monitored by thin-layer chromatography
(TLC) carried out on precoated glass-backed plates Merck 60 HF254 (0.25 mm)
with UV light. Melting points were measured on an Electrothermal 9100 apparatus
(LABEQUIP LTD., Markham, Ontario, Canada) and are uncorrected. FT-IR spectra
of the catalyst ant products were measured on a Jasco 6300 FT-IR spectrometer. Ele-
mental analysis was performed using an inductively coupled plasma optical emis-
1
sion spectroscopy (ICP-OES, Model: VISTA-PRO). H and 13C NMR (DMSO-d6
and CDCl3) spectra were recorded on a Bruker DRX-250 Avance spectrometer at
250.13 and 62.90 MHz, respectively.
Preparation of catalyst
Preparation of CoFe2O4 MNPs
Cobalt ferrite nanoparticles were synthesized by the co-precipitation of Co2+ and
Fe3+ ions (molar ratio 1:2) in sodium hydroxide solution. FeCl3·6H2O (540 mg) and
CoCl2·6H2O (238 mg) were dissolved in 10 mL deionized water. NaOH (1200 mg)
1 3

Magnetic cobalt ferrite nanoparticles functionalized with…
was dissolved in 10 mL deionized water and this solution was added into the pre-
viously prepared solution while stirring at 80 °C. The stirring was continued for
30 min and cooled to room temperature. The black precipitate was isolated in a
magnetic feld, washed with deionized water three times, and fnally dried. Then, the
structure and particle size were obtained by studying the FT-IR, XRPD and SEM.
Preparation of magnetic cobalt ferrite nanoparticles functionalized with citric acid
(CoFe2O4@CA)
Magnetic cobalt ferrite nanoparticles were not directly used as catalyst. Rather, they
were functionalized with citric acid as an acidic functional group during the process
of stratifcation. Mixtures of synthesized CoFe2O4 MNPs (1 g), citric acid (7 g) and
200 mL dry toluene were added to round-bottom fask. The mixture was heated up
to 110–120 °C and was stirred in this temperature for 3 h. Water of stratifcation was
removed from the reaction medium using the Dean-Stark glass device. Meanwhile,
the collected toluene was dried twice and used for the next tests. The resulting nano-
particles were cooled and washed with ethyl acetate and ethanol and then dried at
room temperature.
Ultrasound‑assisted and room temperature synthesis of substituted
3‑pyrrolin‑2‑ones
A solution of aniline (1 mmol), diethyl acetylenedicarboxylate (1 mmol), alde-
hyde derivatives (1 mmol), CoFe2O4@CA (75 mg) and ethanol (4 mL) was soni-
cated under ultrasound irradiation. The same reaction also was conducted without
sonication at room temperature. The progress of the reaction was checked by TLC
(n-Hexane: EtOAc, 10:7). After completion of the reaction, the resulting product
was heated in ethanol. The acidic nanocatalyst was magnetically separated from the
reaction mixture and washed several times with acetone for reuse. Then, the product
was cooled in crushed ice and fltered and the pure product was obtained by recrys-
tallization from hot ethanol.
Melting points and spectral data for representative products
Ethyl 2‑(4‑fuorophenyl)‑4‑hydroxy‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 1), White crystal; m.p: 193–196 °C; Yield: 89%. IR (KBr) (νmax
,
cm−1): 3295, 3066, 2984, 1717, 1499, 1027. 1H NMR (250.13 MHz, CDCl3) δH: 1.19
(t, J=7.00 Hz, 3H), 4.19 (q, J=7.00 Hz, 2H), 5.72 (s, 1H), 6.90–7.45 (m, 9H), 9.06
(br s, 1H). 13C NMR (62.90 MHz, CDCl3) δC: 13.93, 60.86, 61.28, 112.94, 115.63 (d,
2JCF =21.89 Hz), 122.39, 125.99, 129.07, 129.29, 129.08 (d, 3JCF =9.37 Hz), 130.89
(d, 4JCF =3.08 Hz), 136.03, 156.38, 160.58, 162.72, 164.70 (d, 1JCF =23.40 Hz).
Ethyl 2‑(4‑chlorophenyl)‑4‑hydroxy‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 2), White crystal; m.p: 195–198 °C; Yield: 91%. IR (KBr) (νmax
,
1
cm−1): 3307, 3067, 2982, 1733, 1499, 1015. H NMR (250.13 MHz, CDCl3) δH:
1.19 (t, 3H, J=7.00 Hz, 2H), 4.20 (q, J=7.00 Hz, 2H), 5.72 (s, 1H), 7.08–7.74 (m,
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H. Ahankar et al.
9H), 9.07 (br s, 1H). 13C NMR (62.90 MHz, CDCl3) δC: 13.97, 60.83, 61.38, 112.77,
122.26, 126.05, 128.87, 129.08, 133.74, 134.29, 135.93, 156.40, 162.76, 164.81.
Ethyl 2‑(3‑chlorophenyl)‑4‑hydroxy‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 3), White crystal; m.p: 184–187 °C; Yield: 89%. IR (KBr) (νmax
,
1
cm−1): 3302, 3050, 2979, 1725, 1475, 1021. H NMR (250.13 MHz, CDCl3) δH:
1.20 (t, 3H, J=7 Hz, 3H), 4.20 (q, 2H, J=7 Hz, 2H), 5.71 (s, 1H), 7.10–7.48 (m,
9H), 9.17 (br s, 1H); 13C NMR (62.90 MHz, CDCl3) δC: 13.90, 60.87, 61.39, 112.72,
122.14, 125.49, 126.03, 127.88, 128.77, 129.10, 129.93, 134.37, 135.99, 137.35,
156.56, 162.75, 164.83.
Ethyl 2‑(2‑chlorophenyl)‑4‑hydroxy‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 4), White crystal; m.p: 204–207 °C; Yield: 89%. IR (KBr) (νmax
,
cm−1): 3300, 3064, 2986, 1728, 1499, 1076. 1H NMR (250.13 MHz, CDCl3) δH: 1.16
(t, J=7.15 Hz, 3H), 4.16 (q, J=7.15 Hz, 2H), 6.43 (s, 1H), 6.93–7.54 (m, 9H), 9.24
(br s, 1H); 13C NMR (62.90 MHz, CDCl3) δC: 13.73, 56.45, 61.34, 112.5, 119.2,
121.62, 125.82, 126.88, 127.49, 129.03, 129.64, 132.77, 136.05, 157.33, 162.72,
165.22.
Ethyl 2‑(4‑bromophenyl)‑4‑hydroxy‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 5), White crystal; m.p: 190–193 °C; Yield: 87%. IR (KBr) (νmax
,
1
cm−1): 3297, 3052, 2981, 1717, 1499, 1027. H NMR (250.13 MHz, DMSO-d6) δH:
1.06 (t, J=7.00 Hz, 3H), 3.64 (br s, 1H), 4.01 (q, J=7.00 Hz, 2H), 6.05 (s, 1H), 7.07–
7.60 (m, 9H); 13C NMR (62.90 MHz, DMSO-d6) δC: 14.41, 60.23, 60.42, 112.20,
121.46, 122.93, 125.99, 126.70, 129.15, 131.60, 136.03, 142.07, 153.27, 162.36,
164.32.
Ethyl 2‑(3‑bromophenyl)‑4‑hydroxy‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 6), White crystal; m.p: 192–194 °C; Yield: 90%. IR (KBr) (νmax
,
1
cm−1): 3304, 3048, 2980, 1727, 1499, 1023. H NMR (250.13 MHz, CDCl3) δH:
1.22 (t, J=7.13 Hz, 3H), 4.21 (q, J=7.13 Hz, 2H), 5.68 (s, 1H), 7.09–7.48 (m, 9H),
9.16 (br s, 1H); 13C NMR (62.90 MHz, CDCl3) δC: 13.92, 60.80, 61.41, 112.73,
122.13, 122.44, 125.90, 126.04, 129.12, 130.22, 130.80, 131.68, 135.97, 137.58,
156.57, 162.74, 164.84.
Ethyl 4‑hydroxy‑2‑(4‑nitrophenyl)‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 7), Yellow solid; m.p: 181–183 °C; Yield: 88%. IR (KBr) (νmax
,
cm−1): 3299, 3073, 2983, 1732, 1498, 1025. 1H NMR (250.13 MHz, DMSO-d6) δH:
7.06–8.05 (m, 9H), 6.25 (s, 1H), 4.00 (q, J=7.00 Hz, 2H), 3.97 (br s, 1H), 1.05
(t, J=7.00 Hz, 3H); 13C NMR (62.90 MHz, DMSO-d6) δC: 14.39, 60.17, 60.26,
111.53, 122.85, 123.77, 126.03, 129.48, 130.66, 136.42, 145.21, 147.53, 153.98,
162.31, 164.45.
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Magnetic cobalt ferrite nanoparticles functionalized with…
Ethyl 4‑hydroxy‑2‑(3‑nitrophenyl)‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 8), Yellow crystal; m.p: 225–227 °C; Yield: 88%. IR (KBr) (νmax
,
1
cm−1): 3319, 3087, 2982, 1736, 1498, 1022. H NMR (250.13 MHz, CDCl3) δH:
1.46 (t, J=7.25 Hz, 3H), 4.21 (q, J=7.08 Hz, 2H), 5.87 (s, 1H), 7.10–8.24 (m, 9H),
9.09 (br s, 1H); 13C NMR (62.90 MHz, DMSO-d6) δC: 14.30, 60.05, 60.28, 111.72,
122.92, 123.48, 123.63, 126.03, 129.28, 130.34, 134.36, 136.32, 139.78, 147.93,
153.81, 162.25, 164.34.
Ethyl
4‑hydroxy‑2‑(2‑nitrophenyl)‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 9), Yellow crystal; m.p: 203–205 °C; Yield: 86%. IR (KBr) (νmax
,
cm−1): 3294, 3080, 2982, 1732, 1499, 1021. 1H NMR (250.13 MHz, CDCl3) δH: 1.20
(t, J=7.13 Hz, 3H), 4.18 (q, J=7.00 Hz, 2H), 5.65 (s, 1H), 7.08–7.68 (m, 9H), 9.10
(br s, 1H); 13C NMR (62.90 MHz, DMSO-d6) δC: 14.34, 54.98, 60.39, 112.19, 122.58,
125.18, 126.11, 127.84, 129.54, 131.64, 134.21, 136.65, 150.51, 153.85, 160.13, 162.26,
164.83.
Ethyl 4‑hydroxy‑5‑oxo‑1,2‑diphenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxylate (Table 4,
entry 10), White crystal; m.p: 174–177 °C; Yield: 81%. IR (KBr) (νmax, cm−1):
1
3250, 3077, 2970, 1710, 1458, 1090. H NMR (250.13 MHz,, CDCl3) δH: 1.16 (t,
3H, J=7.00 Hz, 3H), 4.17 (q, J=7.00 Hz, 2H), 5.74 (s, 1H), 7.05–7.50 (m, 9H),
9.14 (br s, 1H); 13C NMR (62.90 MHz, CDCl3) δC: 13.91, 61.23, 61.56, 113.19,
122.27, 125.81, 127.53, 128.50, 128.57, 128.94, 135.07, 136.24, 156.36, 162.94,
165.05.
Ethyl 2‑([1,1’‑biphenyl]‑4‑yl)‑4‑hydroxy‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑car‑
boxylate (Table 4, entry 11), White solid; m.p: 222–225 °C; Yield: 90%. IR (KBr)
(νmax, cm−1): 3238, 3030, 2976, 1702, 1485, 1018. 1H NMR (250.13 MHz, CDCl3)
δH: 1.20 (t, J=7.13 Hz, 3H), 4.21 (q, J=7.17 Hz, 2H), 5.79 (s, 1H), 7.08–7.5 (m,
12H), 9.10 (br s, 1H); 13C NMR (62.90 MHz, CDCl3) δC: 14.0, 61.23, 61.31, 113.12,
122.23, 125.85, 126.21, 126.94, 127.38, 127.92, 128.76, 129.01, 1334.04, 136.30,
140.18, 141.28, 156.46, 162.88, 165.09.
Ethyl 4‑hydroxy‑5‑oxo‑1‑phenyl‑2‑(p‑tolyl)‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxylate (Table 4,
entry 12), White crystal; m.p: 202–205 °C; Yield: 78%. IR (KBr) (νmax, cm−1): 3250,
3077, 2970, 1710, 1458, 1090. 1H NMR (250.13 MHz, CDCl3) δH: 1.19 (t, J=7.00 Hz,
3H), 2.25 (s, 3H), 4.18 (q, J=7.00 Hz, 2H), 5.71 (s, 1H), 7.02–7.50 (m, 9H), 9.00 (br
s, 1H); 13C NMR (62.90 MHz, CDCl3) δC: 13.93, 21.11, 61.21, 61.32, 113.24, 122.24,
125.73, 127.36, 128.90, 128.27, 131.93, 136.33, 138.24, 156.30, 162.90, 165.11.
Ethyl 4‑hydroxy‑2‑(4‑(methylthio)phenyl)‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑car‑
boxylate (Table 4, entry 13), Yellow crystal; m.p: 159–161 °C; Yield: 82%. IR
1
(KBr) (νmax, cm−1): 3250, 3077, 2970, 1710, 1458, 1090. H NMR (250.13 MHz,
CDCl3) δH: 1.18 (t, J=7.00 Hz, 3H), 2.38 (s, 3H), 4.17 (q, J=7.00 Hz, 2H), 5.68 (s,
1H), 7.10–7.47 (m, 9H), 9.15. (br s, 1H); 13C NMR (62.90 MHz, CDCl3) δC: 13.98,
1 3

H. Ahankar et al.
15.26, 61.12, 61.27, 113.07, 122.24, 125.84, 126.13, 127.95, 128.96, 131.58, 136.14,
139.00, 156.00, 163.00, 164.81.
Ethyl 4‑hydroxy‑2‑(4‑methoxyphenyl)‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carboxy‑
late (Table 4, entry 14), White crystal; m.p: 150–153 °C; Yield: 80%. IR (KBr) (νmax
,
1
cm−1): 3250, 3029, 2929, 1706, 1458, 1107, 1032. H NMR (250.13 MHz, CDCl3)
δH: 1.20 (t, J=7.25 Hz, 3H), 3.73 (s, 3H), 4.19 (q, J=7.08 Hz, 2H), 5.69 (s, 1H),
6.74–7.46 (m, 9H), 9.15. (br s, 1H); 13C NMR (62.90 MHz, CDCl3) δC: 13.98, 55.16,
61.03, 61.25, 113.21, 113.97, 122.37, 125.80, 126.71, 128.66, 128.94, 136.23, 156.38,
159.52, 162.00, 165.00.
Ethyl 4‑hydroxy‑2‑(4‑hydroxyphenyl)‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carbox‑
ylate (Table 4, entry 15), White solid; m.p: 243–245 °C (dec.); Yield: 82%. IR (KBr)
1
(νmax, cm−1): 3311, 3027, 2990, 1698, 1451, 1071. H NMR (250.13 MHz, DMSO-
d6) δH: 1.10 (t, J=7.00 Hz, 3H), 3.55 (br s, 1H), 3.99 (q,, J=7.00 Hz, 2H), 5.93
(s, 1H), 6.55–7.69 (m, 9H), 9.34 (br s, 1H); 13C NMR (62.90 MHz, DMSO-d6) δC:
14.44, 60.08, 60.78, 112.94, 115.41, 123.03, 125.67, 126.66, 129.03, 129.24, 136.79,
152.57, 157.24, 162.48, 164.27.
Ethyl 4‑hydroxy‑2‑(naphthalen‑1‑yl)‑5‑oxo‑1‑phenyl‑2,5‑dihydro‑1H‑pyrrole‑3‑carbox‑
ylate (Table 4, entry 16), White crystal; m.p: 225–228 °C; Yield: 90%. IR (KBr)
(νmax, cm−1): 3250, 3077, 2970, 1710, 1458, 1090. 1H NMR (250.13 MHz, CDCl3)
δH: 1.13 (t, 3H, J=7.00 Hz, 3H), 4.14 (q, 2H, J=7.00 Hz, 2H), 5.91 (s, 1H), 7.02–
7.47 (m, 12H), 9.18 (br s, 1H); 13C NMR (62.90 MHz, CDCl3) δC: 13.89, 61.26,
61.69, 113.13, 122.24, 123.83, 125.87, 126.38, 127.71, 127.77, 127.89, 128.67,
128.98, 132.46, 133.06, 133.26, 136.27, 156.59, 162.93, 164.11.
X‑ray crystallography
The crystallographic measurement of 4i was performed on a κ-geometry Kuma
KM4–CCD (ω scans) automated four-circle difractometer equipped with a CCD
camera Sapphire2 and graphite monochromatized MoKα radiation (λ=0.71073
Å). The data were collected at 100(2) K by using the Oxford-Cryosystems cooler.
Data were corrected for the Lorentz and polarization efects. Data collection, cell
refnement, data reduction and analysis were carried out with KM-4 software,
CrysAlisCCD and CrysAlisRED [36]. Empirical (multi-scan) absorption correc-
tion was applied. Structure was solved with direct methods using SHELXT-2014
[37] and refned by a full-matrix least-squares technique with the anisotropic ther-
mal parameters for non-H atoms with the use of SHELXL-2014 [38]. All the H
atoms were found in diference Fourier maps and were refned isotropically. In the
fnal refnement cycles, the C-bonded H atoms were repositioned in their calcu-
lated positions and refned using a riding model, with C–H=0.95–1.00 Å, and with
Uiso(H)=1.2Ueq(C) for CH and CH2, and 1.5Ueq(C) for CH3. The hydroxyl H atoms
were refned freely. Figures were made with the Diamond program [39]. Details
of structure refnement are given in the crystallographic information fle (CIF)
1 3

Magnetic cobalt ferrite nanoparticles functionalized with…
deposited with the Cambridge Crystallographic Data Centre (CCDC 1866084) and
provided as Supplementary data.
Crystal data for 4i. C19H16N2O6, Mr =368.34, colorless plate, crystal size
̄
0.52×0.30×0.12 mm, triclinic, space group P 1, a=8.778(2), b=13.299(3),
c=15.042(3) Å, α=106.26(3)°, β=95.44(3)°, γ=93.71(3)°, V=1670.5(7) Å3,
T=100(2) K, Z=4, μ=0.11 mm−1 (for Mo Kα, λ=0.71073 Å), empirical absorp-
tion correction (multi-can), Tmin =0.973, Tmax =1.000, 22884 refections measured,
11994 unique (Rint =0.044), 7705 observed (I>2σ(I)), (sin θ/λ)max =0.844 Å−1, 495
parameters, 0 restraints, R=0.062, wR=0.164 (observed ref.), GOOF=S=1.00,
(Δρmax)=0.51 and (Δρmin)=−0.41 e Å−3.
Results and discussion
CoFe2O4 MNPs characterization
Characterization of magnetic cobalt ferrite nanoparticles functionalized with citric
acid was performed using FT-IR spectroscopy, X-ray powder difraction (XRPD)
pattern, scanning electron microscopy (SEM) and thermogravimetric analysis
(TGA). By taking the FT-IR spectrum from CoFe2O4 MNPs and CoFe2O4@CA
separately, the position and absorption rates of the irradiation associated with the
Co–O and OH bonds on the surface of magnetic cobalt ferrite nanoparticles, the car-
bonyl bonding of the acidic group, C–O bond and OH bonds of citric acid on nano-
particles were determined. The absorption in 602 cm−1 was confrmed the presence
of metal–oxygen bond in the CoFe2O4 MNPs structure. It can also be said that the
average absorbance of 3405 cm−1 was based on magnetic cobalt ferrite nanoparticles
Fig. 1 FT-IR spectra of CoFe2O4 MNPs and CoFe2O4@CA
1 3

H. Ahankar et al.
show the presence of OH groups and the adsorption of moisture at the catalyst level
in Fig. 1.
As shown in Fig. 1, the presence of citric acid on the surface of the magnetic
cobalt ferrite nanoparticles, in the FT-IR spectrum, through peaks appearing in the
3600–2900 cm−1 area of the functional groups of citric acid bound to the desired
nanoparticles, appeared at 1609 and 1397 cm−1 for C=O and C–O bonds of citric
acid compared to the cobalt ferrite magnetic nanoparticle spectrum.
Using XRPD, fuzzy analysis, crystalline structure, and grain size of CoFe2O4
MNPs was performed. In this catalyst, the expansion of the peaks is due to the pres-
ence of nanoparticles. The position and intensity of the difraction peaks (220),
(311), (400), (511), and (440) correspond to the obtained pattern with standard pow-
der difraction (JCPDS) and scientifc documentation [40] and its structure was spi-
nel cubic. By examining the XRPD difraction pattern obtained in both CoFe2O4
and CoFe2O4@CA, the relative position and relative intensity of the peaks, as well
as their coherence, proved the presence of CoFe2O4 in the catalytic structure. From
the comparison of two CoFe2O4 and CoFe2O4@CA difusion patterns, the width of
the peaks and the difraction angle, it was found that the nanoparticles were pro-
tected with citric acid. Considering the scientifc resources and standards, the loca-
tion and intensity of the difusion peaks, all major peaks related to CoFe2O4 are also
observed in the CoFe2O4@CA sample. The average size of nanoparticles using the
Debye–Scherrer equation for CoFe2O4 MNPs 40 nm and nanoparticles functional-
ized with citric acid 25 nm (Fig. 2) were obtained.
Also, the catalyst study was performed by examining SEM (Fig. 3). The SEM
images shows the particle size and external morphology of the nanocatalyst. It can
be seen from the SEM image, the nanoparticles have a crystal spherical shape. The
diameter of the CoFe2O4@CA nanoparticles is about 25 nm.
Fig. 2 XRPD patterns of CoFe2O4 MNPs and CoFe2O4@CA
1 3

Magnetic cobalt ferrite nanoparticles functionalized with…
Fig. 3 SEM images of CoFe2O4@CA
Fig. 4 TGA analyses of CoFe2O4@CA
The amount of citric acid groups on the nanoparticles was measured using
TG–DTA (Fig. 4). In the frst stage, the mass loss of catalyst was about 4.9% in
the range of 25–150 °C, which was attributed to water vaporization (endothermic
efect). The second decrease in the mass of the CoFe2O4@CA curve at tempera-
tures above 150 up to 300 °C was more consistent with the analysis of species
with molecular mass, which could indicate that about 21.0% of the mass belongs
to the citric acid groups (exothermic efect).
1 3

H. Ahankar et al.
Application of CoFe2O4@CA in the ultrasonic‑assisted synthesis of substituted
3‑pyrrolin‑2‑ones
In this part of the research, diferent conditions such as the efect of solvent, the
amount of catalyst and ultrasonic irradiation power were investigated on the synthe-
sis of compound 4b as a pattern reaction using aniline, diethyl acetylenedicarboxy-
late, 4-chlorobenzaldehyde and CoFe2O4@CA nanocatalyst (Scheme 2).
Efect of solvent on the synthesis of 4b product
At frst, we tested the efect of the diferent solvents on the synthesis of 4b product
to fnd the best reaction solvent. We investigated dichloromethane (CH2Cl2), ace-
tonitrile (CH3CN) and ethyl acetate (CH3COOC2H5) and ethanol (C2H5OH) and
methanol (CH3OH) solvents (Table 1). The synthesis of 4b product from aniline 1,
diethyl acetylenedicarboxylate 2, 4-chlorobenzaldehyde 3b and CoFe2O4@CA as
a nanocatalyst in ethanol solvent under ultrasound irradiation was obtained in 91%
yield. As shown in Table 1, entries 1–3 and 5, the yield of reactions in other solvents
was reduced. Thus, ethanol was selected as the best solvent for all of the reactions
(Table 1, entry 4).
The efciency of the ultrasonic irradiation on the synthesis of 4b product
Also, to evaluate of the efciency of the ultrasonic irradiation, 50–150 W of power
was investigated for the synthesis of compound 4b as a sample reaction. By increas-
ing the power of ultrasound from 50 to 100 W, the desired reaction efciency
increased, but with increasing power from 100 to 150 W, no particular efect on the
reaction efciency was created. On the other hand, we found that ultrasonic radiation
Scheme 2 Ultrasonic-assisted synthesis of 4b product
1 3

Magnetic cobalt ferrite nanoparticles functionalized with…
Table 1 The efect of the
Entry
Solvent
Time (min)
Yielda (%)
diferent solvents on the
synthesis of 4b producta
1
2
3
4
5
CH2Cl2
CH3CN
CH3COOC2H5
C2H5OH
CH3OH
35
35
35
35
35
73
75
71
91
78
Reaction conditions: aniline 1 (1 mmol), diethyl acetylenedicarboxy-
late 2 (1 mmol), 4-chlorobenzaldehyde 3b (1 mmol) and CoFe2O4@
CA (75 mg) as a nanocatalyst in various solvents under ultrasound
irradiation (100 W)
aIsolated yield
as green energy has a signifcant efect on the produce of the products. Finally, the
best reaction efciency was obtained with 100 W ultrasonic power (Table 2).
The efect of the catalyst amount on the synthesis of 4b product
Then, we checked the role of the catalyst amount on the synthesis of 4b product in
the ethanol solvent. As can be seen in Table 3, entry 1, the yield of reaction was
obtained 38% without catalyat under ultrasound irradiation (100 W). When the
reaction was carried out with adding catalyst under ultrasound irradiation (100 W)
in 35 min, the yield of reactions were increased (Table 3, entry 1). However with
increasing the catalyst amount to 100 mg, the yield of reaction did not change. We
believe that ultrasonic radiation activates the nanocatalyst.
To check the behavior of types of aldehydes in the synthesis of substituted 3-pyr-
rolin-2-ones, we tested numerous and diverse aldehydes like aromatic aldehydes
with diferent groups in the ortho, meta and para positions, hetero-aromatic, unsatu-
rated and aliphatic aldehydes under the reaction conditions with and without sonica-
tion at room temperature under stirring condition. As demonstrated in Table 4, we
found that the aromatic aldehydes with electron-withdrawing groups reacted faster.
For further investigation, other aldehydes such as trans-cinnamaldehyde, salicyla-
ldehyde, 5-bromosalicylaldehyde 2-hydroxy-1-naphthaldehyde, 4-(dimethylamino)
Table 2 Efciency of the
Entry
Ultrasonic power Time (min.)
(W)
Yielda (%)
ultrasonic irradiation in the
synthesis of 4b product
1
2
3
50
100
150
35
35
35
70
91
93
Reaction conditions: aniline 1 (1 mmol), diethyl acetylenedicarboxy-
late 2 (1 mmol), 4-chlorobenzaldehyde 3b (1 mmol) and CoFe2O4@
CA (75 mg) as a nanocatalyst in ethanol solvent and diferent ultra-
sonic power
aIsolated yield
1 3

H. Ahankar et al.
Table 3 The efect of the
catalyst amount on the synthesis
of 4b product
Entry
Catalyst (mg)
Time (min.)
Yielda (%)
1
2
3
4
5
–
35
35
35
35
35
38
56
71
91
91
25
50
75
100
Reaction conditions: aniline 1 (1 mmol), diethyl acetylenedicarboxy-
late 2 (1 mmol), 4-chlorobenzaldehyde 3b (1 mmol) and CoFe2O4@
CA diferent amounts as a nanocatalyst in ethanol solvent under
ultrasound irradiation (100 W)
aIsolated yield
Table 4 Synthesis of substituted 3-pyrrolin-2-ones with and without sonication
Entry
Ar
Product
With sonicationa
Without sonicationb
Time (min)
Yieldc (%)
Time (min)
Yieldc (%)
1
2
3
4
5
6
7
8
4–F–C6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4 m
4n
4o
4p
30
35
40
25
35
25
65
35
40
40
35
65
70
80
65
35
90
91
89
89
87
92
91
89
87
85
90
82
82
80
85
89
720
720
720
720
720
720
720
720
720
720
720
720
720
720
720
720
89
89
90
88
85
90
88
89
86
81
89
78
82
79
82
90
4–Cl–C6H4
3–Cl–C6H4
2–Cl–C6H4
4–Br–C6H4
3–Br–C6H4
4–NO2–C6H4
3–NO2–C6H4
2–NO2–C6H4
Ph
4–Ph–C6H4
4–Me–C6H4
4–MeS–C6H4
4–MeO–C6H4
4–OH–C6H4
2-Naphthal
9
10
11
12
13
14
15
16
aReaction conditions: aniline 1 (1 mmol), diethyl acetylenedicarboxylate 2 (1 mmol), aldehyde 3a–p
(1 mmol) and CoFe2O4@CA (75 mg) as a nanocatalyst in ethanol solvent (4 mL) under ultrasound irra-
diation (100 W)
bReaction conditions: aniline 1 (1 mmol), diethyl acetylenedicarboxylate 2 (1 mmol), aldehyde 3a–p
(1 mmol) and CoFe2O4@CA (75 mg) as a nanocatalyst in ethanol solvent (4 mL) without sonication at
room temperature under stirring condition
cIsolated yield
benzaldehyde, acetaldehyde, isobutyraldehyde, 3-phenylpropionaldehyde, furfural
and glyoxal under the reaction conditions with or without ultrasound irradiation did
not produce desired product and mixture of several products and starting materials
were observed (based on TLC observations). The yield of some aldehydes under
1 3

Magnetic cobalt ferrite nanoparticles functionalized with…
mentioned reaction conditions such as thiophene-2-carbaldehyde, pyrrole-2-car-
boxaldehyde and formaldehyde were very scanty and no specifc product could be
isolated.
The possible mechanism of one-pot three-component sonochemical synthesis of
substituted 3-pyrrolin-2-ones (4a–p) in the in the presence of CoFe2O4@CA as a
green nanocatalyst is shown in Scheme 3. In beginning, an aromatic aldehyde and
aniline are condensed to imine via the acid-catalysed reaction. Then, diethyl acety-
lenedicarboxylate with water undergoes a nucleophilic addition to give 1,3-dipolar
intermediate and is addition to imine. Finally, the target product with nitrogen-con-
taining fve-membered ring is produced by cyclization.
According to Table 4, the signifcant subject is that ultrasound irradiation could
accelerate all of the reactions considerably to decrease the reaction times. Also, the
yield of reactions with sonication was increased compared with the yield of reac-
tions without sonication. It seems that when ultrasound is passed through a liq-
uid–solid system, bubble cavitation causes a series of unique physical phenom-
ena that can afect the mixture of reaction. High energetic waves are produced by
Scheme 3 The possible mechanism for the synthesis of substituted 3-pyrrolin-2-ones (4a–p)
1 3

H. Ahankar et al.
cavitation. Shockwaves are formed when cavities rapidly expand or collapse. Spheri-
cal particles can be accelerated signifcantly that occurs during the explosive growth
of a cavity on the particle surface. During the collapse of a cavity, high local tem-
peratures and pressures arise which results in a pressure shockwave. We believed
that the ultrasonic irradiation played an important role in this reaction and enabled
the reaction to proceed smoothly under mild conditions. Easy workup procedure,
cleaner reaction profle, use of green and reusable acidic nanocatalyst, short reaction
times and excellent yields are some notable features of this method. Application of
ultrasound irradiation makes this procedure potentially very clean, useful, fast and
convenient. In recent years, there are very few reports on the synthesis of substi-
tuted 3-pyrrolin-2-ones under ultrasound irradiation or in the presence of magnetic
nanoparticles.
Eventually, the recyclability of the catalyst was studied considering its magnetic
nature. The catalyst was separated by an external magnet from the reaction mix-
ture and dried after being washed with ethanol and acetone. The catalyst was used
repeatedly in the conditions obtained in the reaction. In the comparison of the ef-
ciency of the reactions, this catalyst can conduct the reaction up to fve consecutive
times without reducing the activity and loss of the magnetic characteristic of the
reaction (Fig. 5).
The structure of one chosen product, i.e. ethyl 4-hydroxy-2-(2-nitrophenyl)-
5-oxo-1-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate (4i), was confrmed by
single-crystal X-ray analysis. The asymmetric unit of the crystal (centrosymmetric
̄
space group P 1; racemic compound) consists of two diferent molecules, A and B,
of the same chirality (Fig. 6a). The conformations of A and B are almost identi-
cal, which is shown in Fig. 6b and Table 5, and in addition, bears many common
features with the analogous previously reported compounds: 2-phenyl derivative
[41] (CCDC refcode LIFBEJ [42]) and isomorphous to it 2-(4-fuorophenyl) com-
pound [5], and two polymorphs of 2-(2-chlorophenyl) analogue [43]. As in these
compounds, also in 4i, the C(O)OEt group is planar and, along with the N1-bound
phenyl ring, is almost coplanar with the planes of the pyrroline rings (see the
C8–C9–C10–O4, C11–O4–C10–C9, C10–O4–C11–C12 and C7–N1–C6–C1 torsion
angles in Table 5, which are close to 180° or 0°). The molecules have a C=Oester
,
C–OH syn-periplanar arrangement, which is accompanied by the formation of intra-
molecular C–O–H···O=C hydrogen bond stabilizing the planar conformation of
Fig. 5 Reusability of CoFe2O4@
120
90
CA for the synthesis of com-
87
88
88
91
100
80
60
40
20
0
pound 4b
1
2
3
4
5
Number of cycles
1 3

Magnetic cobalt ferrite nanoparticles functionalized with…
Fig. 6 a The asymmetric unit of 4i: molecular dimers built up from two molecules (A and B) of the same
chirality (here R enantiomers showed), joined by the bifurcated O–H···O hydrogen bonds (red dashed
lines), giving rise to R2(4) ring motif. The partial atom-numbering scheme and the symmetry-independ-
2
ent C–H···O hydrogen bonds (black dashed lines) are also shown. Displacement ellipsoids are drawn at
the 50% probability level. b Comparison of the conformations of both molecules. H atoms are omitted
for clarity. The common reference points are pyrroline atoms
Table 5 Selected geometric
Molecule A
Molecule B
parameters (Å, º) for 4i
O1–C7
O2–C8
N1–C7
N1–C6
1.2196(16)
1.3261(17)
1.3752(18)
1.4230(17)
1.4733(17)
−176.84(13)
−174.55(15)
−7.4(2)
116.18(14)
−30.2(2)
177.89(14)
143.18(13)
−102.95(15)
1.2168(16)
1.3265(17)
1.3819(18)
1.4174(18)
1.4777(17)
179.99(13)
175.87(14)
−14.2(2)
121.58(13)
−35.6(2)
179.94(14)
139.23(13)
−106.76(16)
N1–C13
C11–O4–C10–C9
C10–O4–C11–C12
C7–N1–C6–C1
C7–N1–C13–C14
O5–N2–C15–C14
C8–C9–C10–O4
N1–C13–C14–C15
C9–C13–C14–C15
the molecules (see Fig. 6a and Table S1 in supplementary material). The planes of
pyrroline and its Csp3-bound phenyl rings are almost perpendicular to each other,
with the intersection angles of 79.02(2)° in molecule A and 82.66(2)° in B. The
2-NO2 substituent is twisted relative to that Ph ring, which is refected in the value
of O5–N2–C15–C14 torsion angle (-30.2(2)° in A and −35.6(2)° in B). Its orienta-
tion is stabilized by two bifurcated C–H···O hydrogen interactions.
As shown in Fig. 6a, two crystallographically diferent molecules A and B, of
the same chirality, are joined to each other by two bifurcated O–H···O hydrogen
bonds formed between hydroxyl and ester C=O groups. As a result, the homochiral
1 3

H. Ahankar et al.
dimers are built with the intradimeric R2(4) ring motif found in the middle and
2
with the nitrophenyl rings located on the same side of the central planar fragment.
The molecular self-assembly into dimers of this type is a common structural motif
observed in the crystals of similar compounds with the syn mutual arrangement
of C=Oester and C–OH groups. They have been found previously in 2-phenyl ana-
logue [41], 2-(4-fuorophenyl) compound [5] and one of the polymorphic forms
of 2-(2-chlorophenyl) compound [43], while in the other polymorph—the dimers
formed were centrosymmetric (heterochiral). In the crystal lattice, the adjacent
dimers interact with each other via the network of C–H···O and C–H···π contacts
(see Table S1 for the geometry in supplementary material).
Conclusions
In conclusion, magnetic cobalt ferrite nanoparticles functionalized with citric acid
(CoFe2O4@CA) catalyzed synthesis of substituted 3-pyrrolin-2-ones under ultra-
sonic irradiation via a practical and environmentally benign one-pot three-compo-
nent protocol. To the best our knowledge, no reference has been reported for the
synthesis of substituted 3-pyrrolin-2-ones in the presence of magnetic nanoparticles
and the use of ultrasonic irradiation. We reported a novel method includes several
key features such as ultrasonic irradiation, magnetically and reusability of the nano-
catalyst, avoiding hazardous organic solvents, easy work-up and simple separation of
products without need to traditional separation and purifcation method. Ultrasounds
induce a remarkable acceleration for these reactions, the reaction times decreasing
dramatically and the yields increasing considerably.
Acknowledgements This work was supported by the “Iran National Science Foundation”.
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