Fe3-xTixO4-supported sulfamic acid nanoparticles: New magnetic nanocatalyst for the synthesis of hexahydroquinolines

Article abstract of DOI:10.1016/j.jorganchem.2019.05.020

A novel acidic nanocatalytic system, sulfamic acid-functionalized Fe_3-xTi_xO₄ magnetic nanoparticles (MNPs), were synthesized through one-pot reaction of Fe_3-xTi_xO₄ MNPs with 3-chloropropyltrimethoxysilane and imidazolidine-2,4-dione followed by functionalization with chlorosulfonic acid. The structure of this newly synthesized nanocatalyst was established by several analysis methods including, Fourier-transform infrared (FTIR) and energy-dispersive X-ray (EDX) spectroscopies, transmission (TEM) and scanning (SEM) electron microscopies, thermal gravimetric (TG), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The potential catalytic ability of this nanocatalyst was evaluated in one-pot four-component condensation reaction between aromatic aldehydes, dimedone, alkyl acetoacetates and ammonium acetate in order to synthesis of hexahydroquinoline derivatives. The reactions proceeded smoothly under solvent-free condition offering excellent yields of corresponding hexahydroquinolines successfully. In addition, the fabricated nanocatalyst exhibited excellent reusability up to four subsequent runs.

Full text of DOI:10.1016/j.jorganchem.2019.05.020

Accepted Manuscript
Fe Ti O -supported sulfamic acid nanoparticles: New magnetic nanocatalyst for
3-x x 4
the synthesis of hexahydroquinolines
Davood Azarifar, Younes Abbasi, Mehdi Jaymand, Mohammad Ali Zolfigol,
Masoumeh Ghaemi, Omolbanin Badalkhani
PII:
S0022-328X(19)30211-6
DOI:
https://doi.org/10.1016/j.jorganchem.2019.05.020
JOM 20802
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 2 February 2019
Revised Date: 14 May 2019
Accepted Date: 21 May 2019
Please cite this article as: D. Azarifar, Y. Abbasi, M. Jaymand, M.A. Zolfigol, M. Ghaemi, O. Badalkhani,
Fe Ti O -supported sulfamic acid nanoparticles: New magnetic nanocatalyst for the synthesis
3-x x 4
of hexahydroquinolines, Journal of Organometallic Chemistry (2019), doi: https://doi.org/10.1016/
j.jorganchem.2019.05.020.
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ACCEPTED MANUSCRIPT
Fe3-xTixO4-supported sulfamic acid nanoparticles: New magnetic
nanocatalyst for the synthesis of hexahydroquinolines
Davood Azarifar1, Younes Abbasi*,1, Mehdi Jaymand*,2, Mohammad Ali Zolfigol1,
Masoumeh Ghaemi1, and Omolbanin Badalkhani1
1. Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran.
2. Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University
Medical Sciences, Kermanshah, Iran.
*Corresponding
authors:
younes.abbasi@yahoo.com
(Younes
Abbasi)
or
m_jaymand@yahoo.com; m.jaymand@gmail.com (Mehdi Jaymand)

ACCEPTED MANUSCRIPT
Abstract
A novel acidic nanocatalytic system, sulfamic acid-functionalized Fe3-xTixO4 magnetic
nanoparticles (MNPs), was synthesized through one-pot reaction of Fe3-xTixO4 MNPs with
3-chloropropyltrimethoxysilane and imidazolidine-2,4-dione followed by functionalization
with chlorosulfonic acid. The structure of this newly synthesized nanocatalyst was established
by several analysis methods including, Fourier-transform infrared (FTIR) and
energy-dispersive X-ray (EDX) spectroscopies, transmission (TEM) and scanning (SEM)
electron microscopies, thermal gravimetric (TG), X-ray diffraction (XRD), and vibrating
sample magnetometer (VSM). The potential catalytic ability of this nanocatalyst was
evaluated in one-pot four-component condensation reaction between aromatic aldehydes,
dimedone, alkyl acetoacetates and ammonium acetate in order to synthesis of
hexahydroquinoline derivatives. The reactions proceeded smoothly under solvent-free
condition offering excellent yields of corresponding hexahydroquinolines successfully. In
addition, the fabricated nanocatalyst exhibited excellent reusability up to four subsequent
runs.
Keywords: Titanomagnetite; Nanocatalyst; Hexahydroquinolines; Sulfamic acid; Reusability
2

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1. Introduction
Over the last few decades, development of environmentally benign and eco-friendly
processes and catalysts has emerged as increasingly important goal in the chemistry domain
[1, 2]. Recently, an area of intense catalytic endeavor in organic synthesis has emphasized the
use and design of the catalysts immobilized on various nano-sized supports possessing high
performance of catalytic activity and stability compared to unsupported counterparts [3].
Among the solid nanomaterials used as supports for a wide variety of catalysts, magnetic
nanoparticles (MNPs) have attracted great deal of interest as efficient catalysts and supports
throughout the scientific as well as industrial communities due to their unique size, high
surface-to-volume ratio, good biocompatibility, low toxicity, efficient recyclability, and
coordinated parts which provide a larger number of active sites per unit area in comparison
with their corresponding bulk materials [4-18]. Moreover, MNPs can be easily separated
from the reaction mixture simply using an external magnet bar. This strategy avoids the
tedious process of isolation via filtration or centrifugation for such small NPs [19-20].
However, the main problem regarding the application of MNPs is their quick aggregation into
large bunches that leads to lose their unique properties. To circumvent this problem and
preserve their nano-scale properties, their surface is usually shielded with organic (e.g., silan
coupling agent) or inorganic materials (e.g., silica) to form core-shell structures [21, 22].
Among the most extensively studied MNPs as the core magnetic support to immobilize
various catalysts, Fe3O4 [23-27] and Fe2O3 [28-30] NPs have received enormous attention
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because of their simple synthesis, low cost, and relatively large magnetic susceptibility
[31-35]. In addition, the incorporation of Ti4+ cations into the Fe3O4 MNPs structure in order
to produce Fe3-xTixO4 MNPs significantly increase the relative number of surface hydroxyl
groups that lead to improve physicochemical features of the final nanomaterial [23, 26].
A wide variety of pharmacologically active heterocyclic compounds embrace a quinoline
scaffold in their framework [36, 37]. Many of these compounds possesses antibacterial,
anti-hypersensitive, anti-malarial, anti-inflammatory and anti-asthmatic activities [38, 39],
and tyrosine kinase PDGF-RTK inhibiting properties continue to spur synthetic efforts
regarding their acquisition [40, 41]. In addition, quinolones are useful synthons for the
preparation of various industrial products such as nanostructures and polymers with enhanced
electronic, optical and mechanical properties [42]. Therefore, these important industrial,
pharmacological and synthetic values have rendered the quinolones attractive as synthetically
challenging research targets. Various synthetic strategies including, Skraup, Doebner von
Miller, Combs, and Friedländer procedures [43-45], as well as one-pot multi-component
reactions (MCRs) have been introduced for the synthesis of quinolones. Among these, MCRs
catalyzed by various catalysts such as silica-bonded imidazolium-sulfonic acid chloride [46],
hafnium (IV) bis(perfluorooctanesulfonyl)imide complex [47], scandium triflate [48], protic
pyridinium ionic liquid [49], magnetite–ceria nanocatalyst [50], nanometasilica disulfuric
acid and nanometasilica monosulfuric acid sodium salt [51], and ZrO2 nanoparticles [52] are
particular of interest.
In continuation of our ongoing studies towards the development of efficient and
environmentally friendly synthesis of heterogeneous naocatalysts and their application
4

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in organic transformations and heterocyclic compounds synthesis [53-58], herein, we report
the synthesis and characterization of imidazolidine-2,5-dione-1-sulfamic acid-functionalized
Fe3-xTixO4 MNPs (denoted as Fe3-xTixO4-SO3H MNPs) and their application as efficient
nanocatalyst for the synthesis of hexahydroquinolines 5a-m through a one-pot
four-component reaction between aromatic aldehydes, dimedone, alkyl acetoacetates and
ammonium acetate (Scheme 1).
O
O
Ar
O
O
O
O
Cat
OR
NH4OAC
ArCHO
(2a-m)
+
+
+
N
H
OR
(5a-m)
R=Me or Et
Scheme 1. Synthesis of hexahydroquinolines 5a-m catalysed by Fe3-xTixO4-SO3H MNPs.
2. Results and discussion
2.1. Catalyst Characterization
In the present work, we have synthesized Fe3-xTixO4-SO3H as magnetic heterogeneous
nanocatalyst. As illustrated in Scheme 2, we initially synthesized Fe3-xTixO4 MNPs by the
reaction of an equimolar amounts of FeSO4.7H2O and TiCl4 in acidic solution with hydrazine
monohydrate [53]. In the next stage, the surface of Fe3-xTixO4 MNPs were modified using
3-silylpropylhydantoin (SPH) via one-pot reaction with 3-chloropropyltrimethoxysilane and
imidazolidine-2,4-dione (hydantoin). Finally, the resulted NPs were sulfonated by treatment
with chlorosulfonic acid. It is interesting to know that, the presence of Ti+4 cations in the
structure of NPs can increase the number of superficial hydroxyl groups [59], and improve
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the loading capacity of sulfonic acid groups on the surface of the titanomagnetite NPs
(4.1-5.5 mmolg-1) compared with the magnetite Fe3O4 NPs (1.76 mmolg-1) [60], and
magnetite silica-coated Fe3O4 NPs (0.32 mmolg-1) [61].
Scheme 2. Synthesis of Fe3-xTixO4-SO3H MNPs.
The structure of the synthesized nanocatalyst was fully characterized by different analysis
methods including, FTIR spectroscopy, EDX, SEM, TEM, XRD, VSM, and TGA as follows.
The FTIR spectra of the Fe3-xTixO4 NPs (a), SPH-functionalized Fe3-xTixO4 (b), and
Fe3-xTixO4-SO3H MNPs (c) are shown in Figure 1. Comparison between three spectra clearly
confirms the successful conjugation of 3-(3-silyl propyl) hydantoin-1-sulfonic acid onto the
surface of the Fe3-xTixO4 NPs. The peaks shown at 3418, 587 and 796 cm-1 in the FTIR
spectrum of the Fe3-xTixO4 NPs are assigned to the O-H, Fe-O and Ti-O stretching vibrations,
respectively (Figure 1a). Similarly, SPH-functionalized Fe3-xTixO4 and Fe3-xTixO4-SO3H
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exhibited the same stretching vibrations at 3415 (O-H), 684 (Fe-O), 764 (Ti-O) cm-1 (Figure
1b) and 3422 (O-H), 594 (Fe-O), 764 (Ti-O) cm-1 (Figure 1c), respectively. The appearance
of aliphatic C-H stretching vibrations at 2934 to 3058 cm-1 rejoin along with the -CH2
bending vibrations at 1457 and 1460 cm-1 in FTIR spectra provides evidence for the
successful attachment of silylpropyl linker to the surface of the Fe3-xTixO4 NPs.
The successful attachment of the hydantoin moiety onto the surface of these NPs is justified
by the appearance of the absorption bands at 1704 and 1766 cm-1 for the SPH-functionalized
Fe3-xTixO4 and at 1702 and 1743 cm-1 for the Fe3-xTixO4-SO3H MNPs, respectively that
related to the C=O stretching vibrations. In addition, the appearance of two absorption bands
at 988 and 1210 cm-1 in the FTIR spectrum of Fe3-xTixO4-SO3H MNPs (Figure 1c) confirm
the presence of the sulfamic acid groups in the sample.
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Figure 1. FTIR spectra of the Fe3-xTixO4 NPs (a), SPH-functionalized Fe3-xTixO4 (b), and
Fe3-xTixO4-SO3H MNPs (c)
.
The elemental composition of the synthesized Fe3-xTixO4-SO3H nanocatalyst was investigated
using EDX analysis as shown in Figure 2. The EDX analysis clearly indicates the peaks for
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ACCEPTED MANUSCRIPT
Si, Ti, Fe, C, N, S, and O elements that verify the successful formation of Fe3-xTixO4-SO3H
MNPs. The results obtained from EDX analysis is summarized in Table 1.
Figure 2. EDX analysis of Fe3-xTixO4-SO3H nanocatalyst.
Table 1. Results obtained from EDX analysis.
Sample
C (wt%) N (wt%) Si (wt%) O (wt%) Fe (wt%) Ti (wt%) S (wt%)
28.76 13.73 2.81 47.78 0.60 2.46 3.87
Fe3-xTixO4-SO3H
The morphological structure as well as size distribution of the synthesized Fe3-xTixO4-SO3H
nanocatalyst were investigated using SEM as well as TEM analysis as illustrated in Figure 3.
The SEM image exhibited that the catalyst was made up of spherical and nanometer-sized
particles in the range of 35±10 nm. In contrast, the TEM image exhibited spherical core-shell
morphology for these NPs. The average diameters of core and shell are about 60±10 and
70±10 nm, respectively. This morphology as well as diameter can provided high surface area
for the immobilization of organic compounds onto the NPs for efficient catalysis of various
9

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reactions.
Figure 3. SEM (left) and TEM (right) images of the synthesized Fe3-xTixO4-SO3H nanocata-
lyst.
It is well established that the catalytic activity can be strongly affected by crystallinity of the
catalyst. The crystallinity of the synthesized Fe3-xTixO4-SO3H nanocatalyst was studied using
XRD analysis as illustrated in Figure 4. The successful synthesis of crystalline
Fe3-xTixO4-SO3H nanocatalyst was approved through the appearance of some diffraction
peaks at 2θ=30.4, 35.8, 43.5, 53.8, 57.5, and 63.1°. It should be pointed out that the organic
shell around the Fe3-xTixO4-SO3H MNPs act as impurity that reduced the crystallinity of the
nanocatalyst. Despite, the fabricated nanocatalyst has excellent crystallinity according to
XRD pattern.
10

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400
300
200
100
0
5
15
25
35
45
55
65
75
85
2θ (°)
Figure 4. XRD pattern of the synthesized Fe3-xTixO4-SO3H nanocatalyst.
The magnetic properties of the Fe3-xTixO4 MNPs and Fe3-xTixO4-SO3H MNPs were measured
using VSM equipment at 300 K in the applied field sweeping range of -10000 to 10000 Oe.
The saturation magnetization (δs) of the Fe3-xTixO4 MNPs and Fe3-xTixO4-SO3H MNPs were
obtained to be 33.85 and 14.02 emu.g-1, respectively. This reduction in the δs value is origi-
nated from the effective loading of precursors on the surface of Fe3-xTixO4 MNPs that verify
the successful synthesis of Fe3-xTixO4-SO3H MNPs. In spite of this reduction, the catalyst still
retains sufficient magnetism to be efficiently separated from the solution simply using an ex-
ternal magnetic field (Figure 5).
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40
20
0
Fe3-xTixO4 MNPs
Fe3-xTixO4-SO3H MNPs
-20
-40
-10000
-5000
0
5000
10000
Field (Oe)
Figure 5. VSM curves of Fe3-xTixO4 MNPs and Fe3-xTixO4-SO3H MNPs.
The thermal gravimetric (TG) and differential thermal (DT) analyses were performed on the
Fe3-xTixO4-SO3H nanocatalyst to examine its thermal stability (Figure 6). As evidenced from
TGA and DTA curves, the weight loss process of the nanocatalyst is divided into three main
stages. The first stage involves the weight loss at 89 °C due to the loss of adsorbed water or
any organic solvents that used during the synthesis of the nanocatalyst. A significant weight
loss exhibited in the second stage at around 300 °C could be due to the loss of the
immobilized sulfamic acid groups. The third weight loss at 415 °C is attributed to complete
decomposition of organic residue on the surface of the nanocatalyst. According thermal
property study results, the fabricated nanocatalyst has excellent thermal stability even to
apply for various reactions at high temperatures (up to 300 °C).
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Figure 6. TGA (a) and DTA (b) curves of the synthesized Fe3-xTixO4-SO3H nanocatalyst.
2.2. Catalytic activity
The fabricated Fe3-xTixO4-SO3H MNPs were explored as magnetically separable acidic
nanocatalyst for the synthesis of hexahydroquinolines (5a-m) from one-pot four-component
reaction between
aromatic
aldehydes,
dimedone
(5,5-dimethylcyclohexane-
1,3-dione), alkyl acetoacetates and ammonium acetate as illustrated in Scheme 1. In order to
optimize the reaction conditions, the reaction of dimedone 1, 4-chlorobenzaldehyde (2b),
ethyl acetoacetate (3) and ammonium acetate (4) was selected as model reaction. The effects
of different reaction parameters were examined as listed in Table 1. The effect of solvent on
the reaction was evaluated using some solvents including, H2O, EtOH and CHCl3 under the
same amount (0.01 g) of nanocatalyst loading and noticed that solvent-free condition
provided the best result (entry 4). As seen in Table 1, the optimal catalyst loading and
reaction temperature in terms of the reaction time (20 min) and yield (94%) were found to be
0.02 g and 60 °C respectively (entry 5). No improvements of the reaction time and yield were
observed by further increasing the amount of the nanocatalyst (entries 6 and 7) or reaction
temperature (entries 9 and 10). To verify the catalytic importance, the reaction was carried
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out under the optimized conditions in the absence of the catalyst and it was found that the
product was formed in a very low yield (entry 11).
Table 1. Screening the reaction parameters for the model reaction of dimedone,
4-chlorobenzaldehyde, ethyl acetoacetate and ammonium acetate.a
Cl
CHO
O
O
O
O
O
O
Cat
NH4OAC
4
OEt
+
+
+
N
H
Cl
OEt
3
1
2b
5b
Entry
Catalyst (g)
0.01
0.01
0.01
0.01
0.02
0.03
0.04
0.02
0.02
0.02
-
Solvent
Temperature (°C)
Time (min)
Yield (%)b
1
2
H2O
60
60
60
60
60
60
60
RT
90
110
60
60
60
60
20
20
20
20
60
20
20
60
45
61
40
85
94
89
87
56
86
82
15
EtOH
3
CHCl3
4
-
-
-
-
-
-
-
-
5
6
7
8
9
10
11
a Reaction conditions: 4-chlorobenzaldehyde (1 mmol), dimedone (1 mmol), ethyl acetocetate (1 mmol), ammonium acetate
(1.5 mmol), solvent (5 mL).
b Isolated pure yield.
This achievement encouraged us to extend the scope of the described methodology to a series
of variously substituted aromatic aldehydes (2a-m) in reaction with dimedone 1, ethyl or
methyl acetoacetate 3 and ammonium acetate 4 under the optimized conditions (Table 2). As
summarized in Table 2, all the reactions proceeded smoothly to furnish the respective
14

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products in relatively short reaction times with excellent and comparable yields irrespective
of the nature of the substituent groups bonded to the aromatic ring. All the obtained products
(5a-m) were known compounds, which were characterized on the basis of their physical and
1
13
spectral (FTIR, H NMR and C NMR) analysis and compared with the corresponding data
reported in the literature.
Table 2. Fe3-xTixO4-SO3H-catalyzed synthesis of hexahydroquinolines 5a-m under
solvent-free condition at 60 °C. a
O
Ar
O
O
O
O
Cat
OR
NH4OAC
ArCHO
(2a-m)
+
+
+
N
H
O
OR
(5a-m)
R=Me or Et
Entry
Ar
Product
R
Time Yield
Mp (°C)
(min)
25
20
25
25
20
25
25
15
20
15
10
10
15
(%)b
85
94
90
91
93
89
98
96
88
90
94
93
92
Found
Reported
-
1
2
C6H5
5a
5b
5c
5d
5e
5f
Et
Et
Et
Et
Et
Et
Et
Et
225-227
245-247
207-209
204-206
196-299
246-248
264-267
256-258
263-266
245-248
274-277
267-270
271-274
4-ClC6H4
2-ClC6H4
3-ClC6H4
4-FC6H4
245-246 [62]
208-209 [36]
209-211 [63]
184-186 [49]
247-249 [64]
262-264 [49]
256-258 [46]
261-263 [65]
-
3
4
5
6
4-NO2C6H4
4-MeC6H4
4-MeOC6H4
C6H5
7
5g
5h
5i
8
9
Me
Me
Me
Me
Me
10
11
12
13
4-FC6H4
5j
4-MeC6H4
2-MeOC6H3
2-ClC6H4
5k
5l
>270 [66]
-
5m
271-273 [63]
a
Conditions: aldehyde (1 mmol), dimedone (1 mmol), ethyl (or methyl) acetoacetate (1 mmol),
ammonium acetate (1.5 mmol), catalyst (0.02 g), solvent-free, 60 °C.
b Isolated pure yield.
15

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2.3. Reaction mechanism
According to the mechanisms proposed in the literature [36, 46, 65], a plausible reaction
pathway to explain the formation of hexahydroquinolines (5a-m) is depicted in Scheme 3.
First, the Fe3-xTixO4-SO3H-activated dimedone 1 in its enolized form undergoes nucleophilic
condensation with catalyst-activated aldehyde 2 to form the Knoevenagel type intermediate I.
On the other hand, the alkyl acetoacetate 3 undergoes nucleophilic condensation reaction with
ammonium acetate 4 in the presence of the catalyst to produce the enamine intermediate II.
Then, the nucleophilic addition of the enamine II to the catalyst-activated intermediate I
occurs to provide the intermediate III, which undergoes intramolecular nucleophilic
cyclization followed by dehydration to furnish the expected products 5.
Scheme 3. Proposed mechanism for Fe3-xTixO4-SO3H-catalyzed synthesis of the hexahydroquinolines
(5a-m).
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2.4. Recyclability of nanocatalyst
The potential recovery and reusability of the nanocatalyst was investigated for the model
reaction. The nanocatalyst was recovered simply using an external magnet, washed with ethyl
acetate (5 mL) and hot ethanol (10 mL), dried in vacuum at room temperature and reused in
the next 4 subsequent runs. The summarized data in Table 3, demonstrated practical
recyclability of the synthesized nanocatalyst with a slight loss of its activity up to 4 fresh
runs.
Table 3. Recyclability of the Fe3-xTixO4-SO3H nanocatalyst for the model reaction between
4-chlorobenzaldehyde, dimedone, ethyl acetoacetate and ammonium acetate.
Run
Time (min)
Yield (%)a
1
2
3
4
20
20
23
25
94
92
90
87
a Isolated yield.
2.5. Catalyst efficiency
The efficiency of the synthesized Fe3-xTixO4-SO3H nanocatalyst in comparison with some
other catalysts for the synthesis of similar hexahydroquinolines are summarized in Table 4.
As seen, in the case of some products the developed Fe3-xTixO4-SO3H nanocatalyst has higher
catalytic performance than those of the reported in the literatures.
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Table 4. The efficiency of the Fe3-xTixO4-SO3H nanocatalyst in comparison with some other
catalyst that employed to the synthesis of hexahydroquinoline derivatives
.
Sample Catalyst Condition Temperature (°C) Time (min) Yield (%) References
Fe3-xTixO4-SO3H Solvent-free 60
t-BuOK Solvent-free 60
K7[PW11CoO40] CH3CN reflux
Fe3-xTixO4-SO3H Solvent-free 60
K7[PW11CoO40] CH3CN reflux
r.t.
Solvent-free 60 or MW
EtOH r.t.
25
85
73
80
94
85
90
91
88
89
75
80
98
90
89
90
89
90
82
86(82)
86
92
87
96
85
85
5a
5a
5a
5b
5b
5b
5b
5b
5f
Current
120
35
[
[
67
68
]
]
20
Current
30
[
[
[
68
69
70
]
]
]
p-TSA
SSA
EtOH
120
30
ANP
240
25
[71]
Fe3-xTixO4-SO3H Solvent-free 60
Current
Nano MgO
EtOH
reflux
reflux
100
30
[
[
72
68
]
]
5f
K7[PW11CoO40] CH3CN
5f
Fe3-xTixO4-SO3H Solvent-free 60
25
5g
5g
5g
5g
5g
5g
5g
5g
5g
5g
5g
5h
5h
5h
Current
SBA-Pr-SO3H
SO3H-KIT-5
SBISAC
Solvent-free 80
Solvent-free 90
Solvent-free 50
Solvent-free 50
Solvent-free 80
10
[
[
[
[
[
73
74
46
35
75
]
]
]
]
]
70
9
nano-Fe3O4
PPA-SiO2
ANP
7
60
EtOH
r.t.
240
30(35)
5
[71]
DBH or DCH
SnCl2.2H2O
t-BuOK
Solvent-free 130
Solvent-free 80
Solvent-free 60
[
[
[
[
76
77
67
48
]
]
]
]
120
360
15
Sc(OTf)3
EtOH
r.t.
Fe3-xTixO4-SO3H Solvent-free 60
Current
CuO NPs
Solvent-free 140
Solvent-free 60
38
[
[
78
67
]
]
t-BuOK
60
SBA-Pr-SO3H:
sulfonic
acid
functionalized
SBA-15;
ANP:
hreo-(1S,2S)-2-amino-1-(40-nitrophenyl)-1,3-propanediol; p-TSA: p-toluenesulfonic acid; SSA: silica
sulfuric acid; SBISAC: silica-bonded imidazolium-sulfonic acid chloride.
18

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3. Experimental
3.1. General
Melting points were measured in open capillary tubes using a BUCHI 510 apparatus. Fourier
transform infrared (FTIR) spectra were recorded from KBr pellets using a Shimadzu
435-U-04 FTIR spectrophotometer. 1H NMR and 13C NMR spectra were recorded at 250 and
90 MHz, respectively on BRUKER AVANCE instruments using CDCl3 or DSMO-d6 as
solvents at ambient temperature. Scanning electron microscopy (SEM) image was obtained
on a KYKY-EM3200 instrument operated at 26 kV accelerating voltage. Transmission
electron microscopy (TEM) image was captured on a CM10-TH microscope (Philips,
Eindhoven, The Netherlands) with a 100 kV accelerating voltage. Energy-dispersive X-ray
(EDX) analysis of the synthesized nanocatalyst was performed on a FE-SEM TESCAN
MIRA3-FEG instrument. Thermal properties of the nanocatalyst was investigated in air using
TGA/DTA Linseis-181a1750. Magnetic properties of the samples were measured with a
vibrating sample magnetometer (VSM, MDKFT, Iran) at room temperature. Ultrasonication
was performed in a 2200 ETH-SONICA ultrasound cleaner at a frequency of 45 MHz.
3.2. Synthesis of Fe3-xTixO4 MNPs
The Fe3-xTixO4 MNPs were synthesized according to our previously reported procedure [53].
In a round-bottomed glass reactor equipped with a reflux condenser, FeSO4.7H2O (1.90 g, 6.8
mmol) was dissolved in deionized water (10 mL). Afterward, the pH of the solution was
reduced to < 1 using an HCl solution (1 molL-1), then TiCl4 (0.75 mL, 6.8 mmol) and
hydrazine monohydrate (2 mL, 41.2 mmol) were added, respectively. The resulted mixture
was refluxed at 90 °C under nitrogen atmosphere for about 30 minutes followed by
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consecutive dropwise addition a solutions of NaOH (1.60 g) and NaNO3 (0.77 g) in deionized
water (10 mL) under vigorous stirring at a rate of 500 rpm for 1 hour. Afterward, the resulted
mixture was cooled to room temperature, the precipitated Fe3-xTixO4 MNPs were collected
using a magnet bar, washed with deionized water several times, and dried in reduced pressure
at room temperature.
3.3. Synthesis of the (3-silylpropyl)hydantoin-functionalized Fe3-xTixO4
(Fe3-xTixO4-SPH)
The Fe3-xTixO4-SPH MNPs was synthesized as follows. The Fe3-xTixO4 MNPs (1.00 g) were
dispersed in dried pyridine (30 mL) using sonication for 30 minutes. To the resulted mixture
were added a small amount of sodium metal, (3-chloropropyl)-trimethoxysilane (CPTS; 2 mL
10 mmol), and imidazolidine-2,4-dione (hydantoin) (1.50 g, 15 mmol), respectively followed
by refluxing under nitrogen atmosphere for about 24 hours. Eventually, the reaction mixture
was cooled to room temperature to precipitate out the MNPs which were magnetically
separated, washed several times with ethanol and dried in vacuum at room temperature.
3.4. Synthesis of Fe3-xTixO4-SO3H nanocatalyst
The Fe3-xTixO4-SO3H nanocatalyst was synthesized through the solfunation of
Fe3-xTixO4-SPH MNPs. For this purpose, Fe3-xTixO4-SPH MNPs (1.00 g) were dispersed in
dried CH2Cl2 (15 mL) through the sonication for about 30 minutes followed by dropwise
addition of chlorosulfonic acid (1.5 mL, 22.5 mmol). The resulted reaction mixture was
refluxed at room temperature for about 4 hours. At the end of this time, the NPs were
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magnetically separated from the reaction mixture, washed consecutively with CH2Cl2 (2 × 5
mL) and ethanol (3 × 5 mL), and dried in reduced pressure at room temperature.
3.5 General procedure for the synthesis of hexahydroquinoline derivatives
A mixture of dimedone 1 (0.140 g, 1 mmol), aldehyde 2 (1 mmol), ethyl or methyl
acetoacetate 3 (1 mmol), ammonium acetate 4 (0.115 g, 1.5 mmol), and Fe3-xTixO4-SO3H
nanocatalyst (0.02 g) was stirred at 60 °C under solvent-free condition for the appropriate
time (Table 2). After completion of the reaction (monitored by TLC), the reaction mixture
was diluted with hot ethanol (10 mL) and stirred until the solid materials dissolved
completely. The nanocatalyst was recovered magnetically using a magnetic bar. The
remaining supernatant was diluted with water (20 mL) and cooled to room temperature to
precipitate the products 5a-m, which were filtered and purified by recrystallization from a hot
mixed ethanol/water (3:2 v/v) to afford the pure products. All the products synthesized are
known compounds, which were characterized by their melting points and spectral (FTIR, and
1H/13C NMR) analyses and compared with their corresponding data reported in the literature.
Selected physical and spectral data
Ethyl
2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5f)
Yellow solid (342 mg, 89%); m.p. 246–248 °C; FTIR (KBr) ν: 3276, 3187, 3072, 2966, 1703,
1
1651, 1607, 1493, 1344, 1215, 1068, 830, 532 cm-1; H NMR (250 MHz, CDCl3) δ: 0.89 (s,
3H, CH3), 1.06 (s, 3H, CH3), 1.14-1.19 (t, 3H, CH3), 2.08-2.40 (m, 7H, 2CH2, CH3),
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3.99-4.08 (q, 2H, CH2), 5.14 (s, 1H, CH), 6.65 (s, 1H, NH), 7.46-7.49 (d, 2H, Ar-H),
13
8.05-8.08 (d, 2H, Ar-H) ppm; C NMR (62.90 MHz, CDCl3) δ: 14.1, 19.3, 27.0, 29.3, 32.6,
37.2, 40.8, 50.6, 60.0, 104.8, 110.9, 123.3, 128.9, 144.6, 146.1, 149.1, 154.5, 166.8, 195.5
ppm.
Ethyl
4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5h)
Pale yellow solid (355 mg, 96%); m.p. 256–258 °C; FTIR (KBr) ν: 3276, 3204, 3078, 2957,
1701, 1651, 1605, 1496, 1380, 1280, 1215, 1032, 850, 537 cm-1; 1H NMR (250 MHz, CDCl3)
δ: 0.91 (s, 3H, CH3), 1.03 (s, 3H, CH3), 1.18-1.23 (t, 3H, CH3), 2.08-2.31 (m, 7H, 2CH2,
CH3), 3.70 (s, 3H, CH3), 4.02-4.10 (q, 2H, CH2), 4.98 (s, 1H, CH), 6.70-6.73 (d, 2H, H-Ar),
7.04 (s, 1H, NH), 7.19-7.22 (d, 2H, Ar-H) ppm; 13C NMR (62.90 MHz, CDCl3) δ: 14.2, 19.1,
27.0, 29.4, 32.6, 35.7, 40.6, 50.7, 55.0, 59.7, 106.12, 111.9, 113.2, 128.9, 139.7, 143.6, 149.0,
157.7, 167.6, 195.9 ppm.
Methyl
4-(4-fluorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carboxylate (5j)
Pale yellow solid (310 mg, 90%); m.p. 245–248 °C; FTIR (KBr) ν: 3262, 3196, 3072, 2962,
1709, 1679, 1644, 1609, 1501, 1383, 1227, 1169, 1115, 1005, 847, 769, 650, 612, 542 cm-1;
1H NMR (250 MHz, DMSO-d6) δ: 0.80 (s, 3H, CH3), 0.98 (s, 3H, CH3), 1.93-2.47 (m, 7H,
2CH2, CH3), 3.50 (s, 3H, CH3), 4.85 (s, 1H, CH), 6.94-6.97 (d, 2H, Ar-H), 7.12-7.14 (d, 2H,
Ar-H), 9.09 (s, 1H, NH) ppm; 13C NMR (62.90 MHz, DMSO-d6) 18.7, 26.8, 29.5, 32.5, 35.5,
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50.6, 51.1, 103.5, 110.4, 114.7, 115.0, 129.3, 129.4, 144.1, 144.15, 145.9, 149.9, 158.9, 162.8,
167.6, 194.7 ppm.
Methyl
4-(2-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-
3-carboxylate (5l)
White solid (331 mg, 93%); m.p. 267–270 °C; FTIR (KBr) ν: 3283, 3213, 3076, 2957, 1692,
1
1640, 1622, 1609, 1485, 1378, 1218, 1171, 1028, 761, 515 cm-1; H NMR (250 MHz,
DMSO-d6) δ: 0.82 (s, 3H, CH3), 0.97 (s, 3H, CH3), 1.84-2.47 (m, 7H, 2CH2, CH3), 3.45 (s,
3H, CH3), 3.67 (s, 3H, CH3), 5.02 (s, 1H, CH), 6.73-7.02 (m, 4H, Ar-H), 8.96 (s, 1H, NH)
ppm; 13C NMR (62.90 MHz, DMSO-d6) 18.4, 26.6, 29.7, 32.4, 32.9, 50.8, 55.7, 103.4, 109.0,
111.5, 120.1, 127.4, 130.5, 135.4, 144.4, 150.5, 157.4, 168.2, 194.2 ppm.
4. Conclusions
In summary, we have successfully synthesized Fe3-xTixO4-SO3H MNPs as magnetic acidic
nanocatalyst from a simple three-step procedure and fully characterized by FTIR
spectroscopy, EDX, SEM, TEM, XRD, TGA, and VSM analyses. The fabricated MNPs
conveniently catalyzed the one-pot four-component reaction of aromatic aldehydes,
dimedone, ethyl or methyl acetoacetate and ammonium acetate for the synthesis of
hexahydroquinoline derivatives in excellent yields with preserving atom economy. The
prominent advantages of this new protocol are the ease of separation and recyclability of the
nanocatalyst (up to 4 new subsequent runs), operational simplicity, high yields of the
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products, short reaction time, and environmental benignity avoiding toxic reagents and
volatile solvents.
Acknowledgment
The authors wish to thank the Research Council of the Bu-Ali Sina University (Hamedan,
Iran) for instrumental and technical supports to carry out this research.
Note
The authors declare no competing financial interest.
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