Fe3O4 magnetic nanoparticles in the layers of montmorillonite as a valuable heterogeneous nanocatalyst for the one-pot synthesis of indeno[1,2-b]indolone derivatives in aqueous media

Article abstract of DOI:10.1007/s11164-018-3659-7

In the present work, iron oxide nanoparticles (Fe₃O₄-NPs) were prepared using a chemical coprecipitation method. At room temperature, Fe₃O₄-NPs are put in interlamellar space and external surfaces of montmorillonite (MMT) as a supported solid. The MMT@Fe₃O₄ was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA) and Fourier transform infrared spectrophotometry (FT-IR). Then, indeno[1,2-b]indolone derivatives were catalyzed by magnetic MMT@Fe₃O₄-NPs. MMT@Fe₃O₄-NPs were found to be a recoverable organocatalyst for the effective synthesis of the indeno[1,2-b]indolone derivatives via one-pot multicomponent cyclocondensation of ninhydrin, 1,3-diketo compound and amine derivatives in water. The significant advantages of this method are excellent yield, mild conditions, eco-friendly catalyst, low expense, and not using an environmentally harmful catalyst or solvent.

Full text of DOI:10.1007/s11164-018-3659-7

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-018-3659-7
Fe3O4 magnetic nanoparticles in the layers
of montmorillonite as a valuable heterogeneous
nanocatalyst for the one‑pot synthesis of indeno[1,2‑b]
indolone derivatives in aqueous media
Javad Safari1 · Narges Hosseini Nasab1
Received: 26 August 2018 / Accepted: 30 October 2018
© Springer Nature B.V. 2018
Abstract
In the present work, iron oxide nanoparticles (Fe3O4-NPs) were prepared using a
chemical coprecipitation method. At room temperature, Fe3O4-NPs are put in inter-
lamellar space and external surfaces of montmorillonite (MMT) as a supported
solid. The MMT@Fe3O4 was characterized by X-ray difraction (XRD), scanning
electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), vibrating
sample magnetometer (VSM), thermogravimetric analysis (TGA) and Fourier trans-
form infrared spectrophotometry (FT-IR). Then, indeno[1,2-b]indolone derivatives
were catalyzed by magnetic MMT@Fe3O4-NPs. MMT@Fe3O4-NPs were found
to be a recoverable organocatalyst for the efective synthesis of the indeno[1,2-b]
indolone derivatives via one-pot multicomponent cyclocondensation of ninhydrin,
1,3-diketo compound and amine derivatives in water. The signifcant advantages of
this method are excellent yield, mild conditions, eco-friendly catalyst, low expense,
and not using an environmentally harmful catalyst or solvent.
Keywords MMT@Fe3O4 nanoparticles · Organocatalyst · Ninhydrin · Indeno[1,2-b]
indolones · Multicomponent reactions
Introduction
A signifcant type of heterocyclic organic compounds is indeno[1,2-b]indoles.
They have biological and pharmacological applications [1]. Recently, this class of
compounds received considerable attention because they act as lipid peroxidation
inhibitors [2], adenosine triphosphate/guanosine triphosphate-competitive inhibitors
*
Javad Safari
safari@kashanu.ac.ir
1
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan,
Kashan 87317-51167, Islamic Republic of Iran
Vol.:(0123456789)
1 3

J. Safari, N. Hosseini Nasab
of protein kinase (CK2) [3], potassium channel openers [4], and estrogenic agents
[5]. In some of the non-cancer illnesses (neurodegenerative disorders, infammatory
activities, angiogenesis illnesses, and viral infections) and cancer illnesses (such as
prostate, colon, breast and lung cancers), indeno[1,2-b]indoles play a unique role [6,
7]. Because of these great features, we decided to explore the simple and efectual
synthesis of indeno[1,2-b]indolone using MMT@Fe3O4 as a heterogeneous nano-
catalyst under aqueous media.
In the last few years, remarkable regard has been paid to functional metal oxide
nanocrystals such as Fe3O4 nanoparticles (Fe3O4-NPs) because of their prominent
and technological applications as sensors, in clinical use, as catalysts and in high-
density magnetic recording media [8]. Some other properties of Fe3O4-NPs include
use as pigment, ferro fuids, in magnetic drug delivery, magnetic resonance imaging
(MRI), data storage media, and recording material [9, 10].
Montmorillonite K10 (MMT-K10) as a catalyst and catalyst support is an exam-
ple of the use of clays in chemical synthesis that has received special attention [11],
due to their surface area in the range of 750 m2/g and high structural charge (up
to 1000 meq/kg) [12]. MMT-K10 is a nanolayered aluminosilicate clay where one
octahedral alumina sheet is sandwiched between two tetrahedral silica sheets, and
can act as a nanoreactor for the chemical reactions and a drug nanocarrier for phar-
maceutical targets. A large surface area, nonhazardous nature, non-corrosiveness,
low cost, nano-sized, ease of handling, high stability and simple processing are the
featured properties of MMT [13].
In particular, various methods for preparing magnetic NPs have been developed,
including hydrothermal processes [14], the sol–gel method [15], the solvothermal
method [16], and coprecipitation [17]. The simplest, most efcient and most eco-
nomical method is coprecipitation.
In recent years, diferent methods have been introduced for the synthesis of dihy-
droxy indeno[1,2-b]indolone derivatives via multicomponent condensation of aro-
matic anilines, dimedone and ninhydrin as substrates with diferent catalysts such as
SnO2 quantum dots (QDs) [18] and C@TiO2-SO3H-IL1 [19]. However, these meth-
ods have their own merits, while use of an expensive catalyst, high reaction time,
low product yield, and difculties in a work-up procedure are their disadvantages.
There are no examples of the use of MMT@Fe3O4 as a catalyst for the synthesis
of dihydroxy indeno[1,2-b]indolone derivatives in aqueous media. Therefore, we
report, for the frst time, a new, efcient and clean methodology for the synthesis of
dihydroxy indeno[1,2-b]indolone derivatives via three-component condensation of
aromatic anilines, 1,3-diketo compounds, ninhydrin, and MMT@Fe3O4 as a hetero-
geneous catalyst in good yields and shorter reaction time in water (Scheme 1).
1 3

Fe3O4 magnetic nanoparticles in the layers of…
Scheme 1 Synthesis of dihydroxy indeno[1,2-b]indolone derivatives
Experimental section
Materials
All commercially available reagents were used without further purifcation and pur-
chased from Merck and Sigma-Aldrich Company in high purity. The used solvents
were purifed by standard procedure.
Apparatus
Melting points were specifed on an Electrothermal MK3 apparatus using an open-
glass capillary and are uncorrected. Fourier transform infrared spectrophotometry
(FT-IR) spectra were recorded as potassium bromide pellets with a Perkin-Elmer
550 spectrometer. Proton nuclear magnetic resonance (1H NMR) and carbon-13
NMR ( 13C NMR) spectra were obtained in DMSO‐d6 solvent with a Bruker
DRX‐400 and Bruker Avance spectrometer at 400 and 100 MHz, respectively. Ana-
lytical thin-layer chromatography (TLC) was done on 0.2-mm precoated plates of
silica gel 60 F-254 (Merck). The elemental analyses (C, H, N) were obtained from
a Carlo ERBA Model EA 1108 analyzer. Nanostructures were specifed using a
Holland Philips Xpert X-ray powder difraction (XRD) difractometer (CuK, radia-
tion, λ=0.154056 nm), at a scanning speed of 2°/min from 10° to 100° (2θ). Scan-
ning electron microscopy (SEM) analysis was performed on an MIRA3 from the
TESCAN Company. Magnetic properties were determined by a vibrating sample
magnetometer (VSM, MDKFD, University of Kashan, Kashan, Iran) at room tem-
perature. Thermogravimetric analysis (TGA) was performed on a Mettler TA4000
system TG-50 at a heating rate of 10 K min−1 under N2 atmosphere. Energy-disper-
sive X-ray spectroscopy (EDX was carried out using a LEVENS device equipped
with an IDFix detector.
A procedure for MMT@Fe3O4 nanoclay
The MMT@Fe3O4 nanoclay was synthesized by chemical coprecipitation technique
as described in the literature. The details are as follows: 1.0578 g of FeCl2·4H2O was
dissolved in 100 mL of deionized water, 1.00 g of MMT was added to the mixture
for 15 min, and the mixture was stirred for 30 min. Then, 2.5228 g of FeCl3·6H2O
1 3

J. Safari, N. Hosseini Nasab
was dissolved in the suspension by vigorously stirring the mixture solution for
30 min at 80 °C under N2 atmosphere. Under the protection of nitrogen gas, 10 mL
of NH3.H2O was added into the mixture rapidly, and the reaction mixture proceeded
for another hour. Finally, the modifed MMT@Fe3O4-NPs were magnetically sepa-
rated and washed with distilled water and ethanol several times [20].
General procedure for the synthesis of indeno[1,2‑b]indole‑9,10‑diones
A mixture of aromatic amine (1.0 mmol), 1,3-dicarbonyl compound (dimedone or
1,3-cyclohexadione; 1.0 mmol), and MMT@Fe3O4 (0.02 g) were stirred in 5 mL
of water at 70 °C for 5 min. Afterward, ninhydrin (1.0 mmol) was added. After the
completion of the reaction (monitored by TLC with hexane/AcOEt at a ratio of 1:2),
the reaction was allowed to cool and the magnetic catalyst was removed by an exter-
nal magnet. The precipitate was collected by fltration and washed with water multi-
ple times. All of the products were identifed by physical and spectroscopic data as
follows;
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4a): white solid; mp=255–257 °C; IR (KBr): 3476, 3238,
1
2927, 1723, 1608, 1547, 1494, 1451 cm−1; H NMR (400 MHz, DMSO-d6), δ
(ppm): 0.89 (3H, s), 0.96 (3H, s), 1.79 (1H, d, J=16.8 Hz), 1.89 (1H, d, J=15.6 Hz),
2.15 (1H, d, J=14.8 Hz), 2.41 (1H, d, J=17.2 Hz), 5.99 (1H, s), 6.59–6.60 (1H, m),
7.27–7.30 (3H, m), 7.45–7.57 (5H, m), 7.71–7.73 (1H, m).
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4b): white solid; mp=240–242 °C; IR (KBr): 3538, 3368,
2956, 1722, 1551, 1494, 1446 cm−1; 1H NMR (400 MHz, DMSO-d6), δ (ppm): 0.87
(3H, s), 0.93 (3H, s), 1.78 (1H, d, J=17.2 Hz), 1.88 (1H, d, J=15.6 Hz), 2.12 (1H,
d, J=15.6 Hz), 2.40 (1H, d, J=16.8 Hz), 6.03 (1H, s), 6.65 (1H, d, J=7.6 Hz),
7.30–7.33 (3H, m), 7.52–7.60 (4H, m), 7.70–7.71 (1H, d, J=7.2 Hz).
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4c): white solid; mp=160–162 °C; IR (KBr): 3325, 2956,
1727, 1630, 1551, 1491, 1448 cm−1; 1H NMR (400 MHz, DMSO-d6), δ (ppm): 0.87
(3H, s), 0.93 (3H, s), 1.78 (1H, d, J=17.2 Hz), 1.88 (1H, d, J=15.6 Hz), 2.12 (1H,
d, J=15.6 Hz), 2.40 (1H, d, J=16.8 Hz), 6.04 (1H, s), 6.66 (1H, d, J=7.2 Hz), 7.24
(2H, d, J=8 Hz), 7.34 (1H, s), 7.50–7.69 (5H, m).
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]
indole-9,10(6H,9bH)-dione (4d): pale yellow solid; mp=201-205 °C; IR (KBr):
1
3068, 3493, 3376, 2958, 1727, 1529, 1451 cm−1; H NMR (400 MHz, DMSO-
d6), δ (ppm): 0.88 (3H, s), 0.94 (3H, s), 1.81 (1H, d, J=17.2 Hz), 1.90 (1H, d,
J=15.6 Hz), 2.15 (1H, d, J=16 Hz), 2.52 (1H, m), 6.14 (1H, s), 6.64–6.66 (1H, m),
7.53–7.78 (6H, m), 8.30-8.34 (2H, m).
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4e): yellow solid; mp=175-177 °C; IR (KBr): 3317, 2957,
1727, 1610, 1556, 1497 cm−1; 1H NMR (400 MHz, DMSO-d6), δ (ppm): 0.90 (3H,
s), 0.94 (3H, s), 1.85-1.93 (2H, m), 2.17 (1H, d, J=16 Hz), 2.57 (1H, d, J=17.2 Hz),
6.18 (1H, s), 6.67 (1H, d, J=6.8 Hz), 7.53–7.61 (5H, m), 7.70–7.72 (1H, m), 8.34
1 3

Fe3O4 magnetic nanoparticles in the layers of…
(2H, d, J=8.8 Hz). 13C NMR (100 MHz, DMSO-d6): 26.0, 29.4, 33.7, 37.1, 51.1,
97.4, 107.7, 123.3, 124.4, 124.5, 129.0, 130.4, 134.5, 135.2, 142.9, 145.8, 146.8,
162.2, 189.9, 197.2. Anal. calcd. for C23H20N2O6: C 65.71, H 4.79, N 6.66%. Found:
C 65.70, H 4.81, N 6.68%.
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4f): white solid; mp=241–243 °C; IR (KBr): 3416, 2957, 1714,
1601, 1569, 1447 cm−1; 1H NMR (400 MHz, DMSO-d6), δ (ppm): 0.84 (3H, s), 0.95
(3H, s), 1.92–2.05 (4H, m), 5.98 (1H, s), 6.65 (1H, m), 7.36 (1H, s), 7.36–7.54 (5H,
m), 7.71 (1H, m), 7.81 (1H, d, J=7.2 Hz).
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4g): yellow solid; mp=205–207 °C; IR (KBr): 3641, 3459,
1
3349, 3162, 2957, 1712, 1618, 1592, 1444 cm−1; H NMR (400 MHz, DMSO-d6),
δ (ppm): 0.83 (3H, s), 0.94 (3H, s), 1.85–1.95 (2H, m), 2.07 (1H, d, J=16 Hz), 2.15
(1H, d, J=17.2 Hz), 5.77 (1H, s), 6.67 (1H, d, J=6.4 Hz), 6.84 (1H, d, J=7.6 Hz),
6.92–7.01 (2H, m), 7.26 (1H, t, J=7.2 Hz), 7.49 (2H, m), 7.59 (1H, d, J=7.2 Hz),
7.66 (1H, d, J=6.4 Hz), 9.41 (1H, s). 13C NMR (100 MHz, DMSO-d6): 27.4, 28.7,
33.1, 36.3, 51.3, 83.2, 95.9, 104.0, 115.7, 118.9, 122.6, 122.7, 124.6, 129.6, 131.2,
134.6, 148.0, 154.2, 165.0, 188.8, 198. Anal. calcd. for C23H20N2O6: C 70.58, H 5.41,
N 3.58%. Found: C 70.57, H 5.44, N 3.56%.
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4h): brown solid; mp=258–260 °C; IR (KBr): 3321, 2927,
1721, 1603, 1552, 1455 cm−1; 1H NMR (400 MHz, DMSO-d6), δ (ppm): 0.85 (3H,
s), 0.93 (3H, s), 1.78 (1H, d, J=16.8 Hz), 1.87 (1H, d, J=15.6 Hz), 2.09 (1H, d,
J=16 Hz), 2.26 (1H, d, J=17.2 Hz), 5.88 (1H, s), 6.71 (1H, d, J=7.6 Hz), 6.82 (2H,
d, J=8.4 Hz), 7.02–7.08 (3H, m), 7.52 (1H, d, J=7.2 Hz), 7.57 (1H, d, J=7.2 Hz),
7.69 (1H, d, J=7.6 Hz), 9.77 (1H, s). 13C NMR (100 MHz, DMSO-d6): 26.6, 29.2,
33.2, 36.8, 51.1, 83.2, 96.3, 104.5, 115.3, 123.0, 125.1, 126.6, 130.0, 134.6, 134.7,
147.2, 157.1, 163.9, 188.8, 197.6. Anal. calcd. for C23H20N2O6: C 70.58, H 5.41, N
3.58%. Found: C 70.57, H 5.43, N 3.60%.
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4i): white solid; mp=235–238 °C; IR (KBr): 3465, 3241,
2947, 1724, 1605, 1548 cm−1; 1H NMR (400 MHz, DMSO-d6), δ (ppm): 1.77–1.79
(2H, m), 1.94–1.98 (1H, m), 2.10–2.14 (2H, m), 2.38–2.42 (1H, m), 5.96 (1H, s),
6.60 (1H, d, J=6.8 Hz), 7.21 (1H, s), 7.3 (2H, d, J=6 Hz), 7.46–7.52 (5H, m), 7.70
(1H, d, J=7.2 Hz).
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4j): white solid; mp=205–208 °C; IR (KBr): 3462, 3180,
1
1729, 1602, 1550 cm−1; H NMR (400 MHz, DMSO-d6), δ (ppm): 1.78 (2H, m),
2.01 (3H, m), 2.40 (1H, m), 6.01 (1H, s), 6.66 (1H, d, J=7.2 Hz), 7.29 (1H, s), 7.33
(2H, d, J=8 Hz), 7.55 (3H, m), 7.70 (1H, d, J=6.8 Hz).
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4k): white solid; mp=202–204 °C; IR (KBr): 3190, 1730,
1
1598, 1546, 1491 cm−1; H NMR (400 MHz, DMSO-d6), δ (ppm): 1.78 (2H, m),
1.96–2.00 (1H, m), 2.10 (2H, m), 2.37–2.44 (1H, m), 6.00 (1H, s), 6.66 (1H, d,
J=7.2 Hz), 7.26 (3H, m), 7.52–7.71 (5H, m).
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J. Safari, N. Hosseini Nasab
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4l): white solid; mp=234–236 °C; IR (KBr): 3170, 2927,
1724, 1559, 1509, 1462 cm−1; 1H NMR (400 MHz, DMSO-d6), δ (ppm): 1.76 (2H,
m), 1.93–2.10 (3H, m), 2.37 (4H, s), 5.91 (1H, s), 6.65 (1H, d, J=7.2 Hz), 7.13 (1H,
s), 7.17 (2H, d, J=7.6 Hz), 7.27 (2H, d, J=8 Hz), 7.51–7.57 (2H, m), 7.70 (1H, d,
J=7.2 Hz).
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4m): yellow solid; mp=195–197 °C; IR (KBr): 3345, 2946,
1
1719, 1614, 1550, 1511 cm−1; H NMR (400 MHz, DMSO-d6), δ (ppm): 1.76
(2H, m), 1.92–1,97 (1H, m), 2.08 (2H, m), 2.30–2.34 (1H, m), 3.79 (3H, s), 5.91
(1H, s), 6.68 (1H, d, J=7.2 Hz), 7.01 (2H, d, J=8 Hz), 7.11 (1H, s), 7.19 (2H, d,
J=7.2 Hz), 7.51–7.57 (1H, m), 7.70 (2H, d, J=6.8 Hz).
4b,9b-Dihydroxy-7,7-dimethyl-5-phenyl-4b,5,7,8-tetrahydroindeno[1,2-b]indole-
9,10(6H,9bH)-dione (4n): white solid; mp=234–236 °C; IR (KBr): 3160, 2928,
1
1724, 1545, 1469 cm−1; H NMR (400 MHz, DMSO-d6), δ (ppm): 1.10 (3H, s),
1.71–1.78 (2H, m), 1.93–1.98 (2H, m), 2.11–2.14 (2H, m), 2.32 (3H, s), 5.85 (1H,
s), 6.65 (1H, m), 7.03 (1H, s), 7.16–7.21 (2H, m), 7.50–7.55 (3H, m), 7.72 (1H, m).
Results and discussion
Characterization of magnetic MMT@Fe3O4‑NPs
The magnetically heterogeneous organocatalyst, MMT@Fe3O4-NPs, was character-
ized by XRD, SEM, EDX, VSM and FT-IR spectroscopy.
The FT-IR spectra of Fe3O4, MMT, and MMT@Fe3O4 are shown in Fig. 1. The
band around 916 cm−1 was attributed to Al–Al–OH due to of the large rate of Al
in the octahedral site of oxygen. The band at 522 cm−1 was assigned to Si–O–Al.
Hydroxyl stretching vibration of structural MMT was discovered at 3422 cm−1. The
Fe–O stretching vibration bond was observed at 577 cm−1. The bending modes of
Al–Mg–OH and Si–O–Fe are found at 845 and 469 cm−1, respectively. The band at
1402 cm−1 can be assigned to N–H in the MMT-Fe3O4 structure. All three FT-IR
spectra confrm the presence of Fe3O4-NPs on the MMT. Thus, the magnetic nano-
composite (NC) is stable during the synthesis of indeno[1,2-b]indole derivatives in
aqueous media.
The XRD patterns of MMT@Fe3O4 are displayed in Fig. 2. All of the charac-
teristic peaks of magnetic Fe3O4-NPs are existent in the difraction pattern and the
difraction peaks match with the standard XRD pattern (JCPDS fle no. 75-0449),
relevant to the crystalline structure with a spinel structure. The well-defned peaks
are shown at 5.8°, 17.7°, 19.8°, 29.5°, 34.9°, 36.0°, 54.0° and 61.9° related to the
hexagonal structure of MMT. According to XRD pattern, 2θ=20.8° and 26.6° dis-
play quartz in MMT.
As illustrated in Fig. 3, the SEM image specifed the microstructures and mor-
phologies of the sample. The obtained SEM images of NPs intelligibly showed
that Fe3O4-NPs were properly composed with the surface of MMT. Thus,
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Fe3O4 magnetic nanoparticles in the layers of…
Fig. 1 FT-IR spectra of Fe3O4,
MMT, and MMT@Fe3O4
MMT@Fe3O4 composite was successfully synthesized according to these results.
The EDX image in Fig. 4 identifes the elemental oxygen and iron in Fe3O4-NPs,
and carbon, sodium, silicon, aluminum and magnesium in MMT. So, the pres-
ence of elemental compounds in the MMT and Fe3O4-NPs without any impurity
peaks is clearly seen in this spectrum. Figure 5 presents the VSM results to exam
the magnetic properties of MMT@Fe3O4 NCs and Fe3O4 being trapped in the
MMT layers. TGA of the MMT@Fe3O4 NC is shown in Fig. 6. The weight loss
below 200 °C could be assigned the evaporation of adsorbed water. The weight
loss observed at 200–400 °C in the TGA curve is mainly related to the desorption
of crystal water. The fnal mass loss at temperatures ranging from 550 to 750 °C
confrmed the loss of structural hydroxyl groups.
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J. Safari, N. Hosseini Nasab
Fig. 2 The X-ray difraction patterns of MMT@Fe3O4
Fig. 3 The SEM image of
MMT@Fe3O4
Investigation of catalyst activity
At frst, we selected a model reaction containing ninhydrin, dimedone and aniline
in the presence of MMT@Fe3O4 as a magnetic NC. Some previous work for the
formation of indeno[1,2-b]indole derivatives was performed to compare the infu-
ence of MMT@Fe3O4 against reported catalyst in the literature. The outcomes are
shown in Table 1. MMT@Fe3O4 was recognized to be an efcient catalyst because
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Fe3O4 magnetic nanoparticles in the layers of…
Fig. 4 EDX spectrum of MMT@Fe3O4
Fig. 5 The VSM curve of MMT@Fe3O4
Fig. 6 The TGA curve of MMT@Fe3O4
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J. Safari, N. Hosseini Nasab
Table 1 Comparison of
results for the synthesis of
indeno[1,2-b]indoles with
various catalysts
Entry
Catalyst
Time
Yield (%)a/Ref
1
2
3
SnO2 QDs
C@TiO2-SO3H-IL1
MMT@Fe3O4
2.5 h
1 h
20 min
89/[18]
92/[19]
97/This work
aIsolated yield
it improved the reaction time and yield. To investigate the optimal amount of the
catalyst, the reaction was done in the presence of diferent amounts of NC (Table 2).
As shown in Table 2, the best amount of the catalyst was 0.02 g and in the absence
of a magnetic catalyst, no product was gained. Our studies demonstrated MMT@
Fe3O4 has supreme catalytic activity for the synthesis of indeno[1,2-b]indolines
compared to another catalyst. This is because MMT@Fe3O4 containing MMT has
active magnetite sites. Accordingly, MMT@Fe3O4 was chosen for this synthesis
because it is obvious its catalytic system speeds up the reaction. Thereafter, the
reaction was tested in diferent solvents such as H2O, EtOH, H2O/EtOH, CH3CN,
dimethylformamide (DMF) and toluene. The results are summarized in Table 3. It
is clear that polar solvents versus non-polar solvents gave more yields. Among the
polar solvents, water had the best efect. After that, we performed the model reaction
at diferent temperatures (r.t., 50, 60, 70, 100 °C) in water. The results are summa-
rized in Table 4. As shown in Table 4, one of the important factors in the speed and
efciency of the reaction is the efect of the reaction temperature. The best tempera-
ture for this reaction was 70 °C; below this temperature, there was not much prod-
uct and no signifcant changes in the reaction efciency were observed at the refux
temperature.
In continuation of our research, after the optimization of all the reaction param-
eters, a series of diferent amines with the electron-donating and electron-withdraw-
ing groups were used to investigate these three-component reactions under MMT@
Fe3O4 catalysis. It is absolutely clear that using aromatic amine derivatives with the
electron-donating group such as OH, CH3 and OCH3 reacted better than aromatic
amine derivatives with an electron-withdrawing group and unsubstituted aromatic
amine (Table 5).
Table 2 Optimization amount of
Entry
Amount of catalyst Time
(g)
Yield (%)a
MMT@Fe3O4 catalyst
1
2
3
4
5
0
24 h
3 h
1.5 h
30 min
45 min
Trace
56
80
92
90
0.005
0.01
0.02
0.03
Reaction conditions: aniline (1 mmol), dimedone (1 mmol), ninhy-
drin, 5 ml of H2O
aIsolated yield
1 3

Fe3O4 magnetic nanoparticles in the layers of…
Table 3 The efect of diferent
Entry
Solvent
Time (min)
Yield (%)a
solvents in the synthesis of 4a
1
2
3
4
5
6
H2O
EtOH
H2O/EtOH(1:1)
CH3CN
DMF
30
70
60
65
80
80
92
35
40
50
20
28
Toluene
Reaction conditions: aniline (1 mmol), dimedone (1 mmol), ninhy-
drin, MMT@Fe3O4 (0.02 g)
aIsolated yield of the pure compound
Table 4 Efect of temperature
Entry
Temperature
Time (min)
Yield (%)a
on the yield of reaction
1
2
3
4
5
r.t
240
180
90
30
45
25
45
82
92
90
50
60
70
100
Reaction conditions: aniline (1 mmol), dimedone (1 mmol), ninhy-
drin, MMT@Fe3O4 (0.02 g), water (5 ml)
aIsolated yield of the pure compound
Reusability test of magnetic catalyst
A very important factor of magnetic heterogeneous NC is its level of reusability
and ease of recovery. To illuminate this issue, the reaction was carried out under
identical conditions in the presence of a reusable catalyst. After completion of
the reaction, the catalytic system was separated from the reaction mixture by an
external magnet, washed with water several times, air-dried and reused directly
with fresh substrates under similar conditions without considerable loss of cata-
lytic activity (Fig. 7).
The proposed reaction mechanism
The probable mechanism for the formation of indeno[1,2-b]indolines is indicated
in Scheme 2. At the outset, the reaction likely proceeds via MMT@Fe3O4 cata-
lyzing the condensation of 1,3-diketo compound and amine to form intermedi-
ate I (enaminone). Fe3O4-NPs, as powerful Lewis acids, promoted the conden-
sation between 1,3-diketo compound and amine derivatives, by enhancing the
electrophilicity of carbonyl groups. In the next step, MMT@Fe3O4 helped the
reaction between intermediate I and ninhydrin by Michael addition to form inter-
mediate II. In the fnal step, intramolecular electrophilic cyclization generated
1 3

J. Safari, N. Hosseini Nasab
Table 5 Synthesis of indeno[1,2-b]indole derivatives 4a
Entry R1
R2
Product Time (min) Yield (%)b Melting point (oC) Melting point (oC)
[Ref.]
1
2
3
4
5
6
7
8
H
4-Cl
4-Br
3-NO2
4-NO2
2-Cl
2-OH
4-OH
H
4-Cl
4-Br
4-CH3
4-OCH3
2,4-(CH3)2
CH3 4a
CH3 4b
CH3 4c
CH3 4d
CH3 4e
CH3 4f
CH3 4g
CH3 4h
30
35
35
35
40
30
35
20
30
35
35
20
20
20
92
90
90
89
90
87
92
94
92
91
90
96
97
97
255–257
240–242
160–162
201–205
175–177
241–243
205–207
258–260
235–238
198–200
202–204
234–236
195–197
234–236
210–212 [18]
238–240 [18]
160–162 [18]
170–172 [18]
New
230–231 [19]
New
New
218–220 [18]
170–172 [21]
200 [21]
228–231 [22]
194–196 [18]
230–233 [21]
9
H
H
H
H
H
H
4i
4j
4k
4l
4m
10
11
12
13
14
4n
aaniline (1 mmol), 1,3-diketo compound (1 mmol), ninhydrin (1 mmol), MMT@Fe3O4 (0.02 g), water
(5 ml)
bIsolated yield of the pure compound
Fig. 7 Reusability results of nanocatalyst in the model reaction (4a)
1 3

Fe3O4 magnetic nanoparticles in the layers of…
Scheme 2 Proposed reaction mechanism for the synthesis of indeno[1,2-b]indoline derivatives
fve-membered rings, which was a result of reaction between MMT@Fe3O4 and
intermediate II.
Conclusion
In this paper, magnetic organocatalyst (MMT@Fe3O4) as a heterogeneous, easy-to-
prepare, reusable, low-cost and nontoxic catalyst was utilized for the synthesis of
indeno[1,2-b]indole derivatives. This novel procedure provides many advantages,
including the use of a green solvent (H2O), being a simple and environmentally
benign method, easy isolation, shorter reaction time and higher yield than available
methods. The development of green chemistry methods using this catalytic system
is a promising and expedient approach.
Acknowledgements The authors gratefully acknowledge the fnancial support from the University of
Kashan for supporting this work by Grant No. 363022/12.
1 3

J. Safari, N. Hosseini Nasab
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