Synthesis and application of novel 1,2,3-triazolylferrocene-containing ionic liquid supported on Fe3O4 nanocatalyst in the synthesis of new pyran-substituted Betti bases

Article abstract of DOI:10.1002/aoc.4701

A novel magnetic ferrocene-labelled ionic liquid based on triazolium, [Fe₃O₄@SiO₂@Triazol-Fc][HCO₃], has been synthesized and has been successfully introduced as a recyclable heterogeneous nanocatalyst. The cata

Full text of DOI:10.1002/aoc.4701

Received: 4 August 2018
DOI: 10.1002/aoc.4701
Revised: 19 October 2018
Accepted: 19 October 2018
F U L L P A P E R
Synthesis and application of novel 1,2,3‐triazolylferrocene‐
containing ionic liquid supported on Fe3O4 nanocatalyst in
the synthesis of new pyran‐substituted Betti bases
Mahdi Gholamhosseini‐Nazari1 | Somayeh Esmati1 | Kazem D. Safa1
Reza Teimuri‐Mofrad1
| Alireza Khataee2 |
1 Department of Organic and
A novel magnetic ferrocene‐labelled ionic liquid based on triazolium,
[Fe3O4@SiO2@Triazol‐Fc][HCO3], has been synthesized and has been success-
fully introduced as a recyclable heterogeneous nanocatalyst. The catalytic
activity of the novel magnetic nanoparticles was evaluated in the one‐pot
three‐component synthesis of a wide variety of Betti bases. A simple, facile
and highly efficient green method has been developed for the synthesis of kojic
acid‐containing Betti base derivatives at room temperature. Additionally, this
new protocol has notable advantages such as short reaction times, green
reaction conditions, high yields and simple workup and purification steps.
Also, the novel nanocatalyst could be easily recovered using an external mag-
netic field and reused for six consecutive reaction cycles without significant
loss of activity. The newly synthesized nanocatalyst was characterized using
Fourier transform infrared spectroscopy, X‐ray diffraction, energy‐dispersive
X‐ray spectroscopy, field emission scanning electron microscopy, transmission
electron microscopy and Brunauer–Emmett–Teller measurements.
Biochemistry, Faculty of Chemistry,
University of Tabriz, Tabriz 5166614766,
Iran
2 Research Laboratory of Advanced Water
and Wastewater Treatment Processes,
Department of Applied Chemistry,
Faculty of Chemistry, University of
Tabriz, 51666‐16471 Tabriz, Iran
Correspondence
Kazem D. Safa, Department of Organic
and Biochemistry, Faculty of Chemistry,
University of Tabriz, Tabriz 5166614766,
Iran.
Email: dsafa@tabrizu.ac.ir
Funding information
University of Tabriz
KEYWORDS
Betti base, ferrocene, kojic acid, magnetic nanocatalyst, triazole
1 | INTRODUCTION
separations, drug delivery, magnetic resonance imaging,
hyperthermia and catalytic processes.[8–15]
In recent years, supported heterogeneous catalysts as
reusable and environmentally friendly materials have
played a key role in modern science and technology,
especially in organic syntheses.[1–3] Because of the
advantages of catalysts immobilized on solid supports,
such as easy handling, non‐toxicity, low solubility and
increased selectivity, these types of heterocatalysts have
been widely studied.[4] Catalysts immobilized on nano-
structure supports are more attractive because of their
higher activity, selectivity and easy recyclability.[5–7]
Nowadays, magnetic nanoparticles are applied in
various industrial and biological fields such as bio‐
Multicomponent reactions have major roles in organic
synthesis[16] because of their advantages such as high atom
efficiency, environmental friendliness, time and energy
saving and quick and simple performance.[17–20] One of
the important multicomponent reactions is the Betti reac-
tion which was introduced by Mario Betti.[21,22] After the
initial report of the synthesis of Betti bases, the study of
these compounds has become an important area,[23–26]
because of their significant biological,[27,28] synthetic[29–32]
and catalytic[33] applications.
Pyran‐annulated heterocyclic compounds have
attracted considerable attention because of their various
Appl Organometal Chem. 2019;e4701.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4701

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GHOLAMHOSSEINI‐NAZARI ET AL.
useful biological and pharmaceutical activities. Pyrans
and fused pyran derivatives are known to exhibit anti‐
HIV,[34] antifungal,[35] antimicrobial,[36] antiviral and
anti‐inflammatory,[37] antidiabetic[38] and antioxidant[39]
activities. Additionally, pyran‐based scaffolds show
promising anticancer activities which encouraged many
researchers to investigate the synthesis of these types of
compounds as antitumour drug candidates.[40] Kojic acid
and its derivatives are an important class of pyran‐
annulated heterocycles which can be found in natural
and synthetic compounds.[41,42] Therefore, the develop-
ment of novel methods for the efficient and convenient
SCHEME 1 Three‐component
synthesis of pyran‐substituted Betti bases
catalysed by [Fe3O4@SiO2@Triazol‐Fc]
[HCO3] nanocatalyst at room temperature
SCHEME 2 Synthesis of [Fe3O4@SiO2@Triazol‐Fc][HCO3] nanoparticles

GHOLAMHOSSEINI‐NAZARI ET AL.
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synthesis of libraries of these compounds is an
important field for modern medicinal and combinatorial
chemists.
In continuation of our recent studies on the modifica-
tion and development of multicomponent reactions,[43,44]
and the design and synthesis of ferrocene‐containing
magnetic nanocatalysts[45–48] and Betti bases,[49–53] herein
we introduce a new 1,2,3‐triazolylferrocene‐containing
ionic liquid nanocatalyst stabilized on silica‐coated
Fe3O4 ([Fe3O4@SiO2@Triazol‐Fc][HCO3]). We also
report a simple and efficient protocol for the three‐
component one‐pot synthesis of pyran‐containing Betti
base derivatives catalysed by [Fe3O4@SiO2@Triazol‐Fc]
[HCO3] at room temperature (Scheme 1).
FIGURE 1 FT‐IR spectra of (a) Fe3O4, (b) Fe3O4@SiO2, (c)
Fe3O4@SiO2@(CH2)3Cl, (d) [Fe3O4@SiO2@Triazol‐Fc][Cl] and (e)
[Fe3O4@SiO2@Triazol‐Fc][HCO3] nanoparticles
2 | RESULTS AND DISCUSSION
This research was performed in two stages. The first
challenge of this work was the synthesis of the [Fe3O4@
SiO2@Triazol‐Fc][HCO3] nanocatalyst. In the second
stage, pyran‐containing Betti base derivatives were
FIGURE 2 EDX analysis of (a) [Fe3O4@SiO2@Triazol‐Fc][Cl]
and (b) [Fe3O4@SiO2@Triazol‐Fc][HCO3]
FIGURE 3 XRD patterns of (a) [Fe3O4@SiO2@Triazol‐Fc][Cl]
and (b) [Fe3O4@SiO2@Triazol‐Fc][HCO3]

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GHOLAMHOSSEINI‐NAZARI ET AL.
successfully synthesized using the [Fe3O4@SiO2@Triazol‐
Fc][HCO3] nanocatalyst at room temperature.
Initially, magnetite (Fe3O4) nanoparticles were pre-
pared and coated with SiO2 and subsequently modified
Fe3O4@SiO2 core–shell magnetic nanoparticles are
related to the asymmetric stretching vibrations of
Si&bond;O&bond;Si. In the FT‐IR spectrum of
[Fe3O4@SiO2@Triazol‐Fc][Cl] the absorption peaks at
1643 and 1549 cm−1 are due to the stretching vibration
of C&dbond;N and C&dbond;C bonds on aromatic rings.
In addition, at 2923 cm−1 the asymmetric stretching
vibration of aliphatic C&bond;H appeared. An absorption
peak appeared at above 3000 cm−1 related to the
stretching vibration of aromatic C&bond;H on triazol
and ferrocene groups. Finally, the absorption peak at
about 3400 cm−1 is related to O&bond;H group
vibrations. Accordingly, in FT‐IR spectrum of the
[Fe3O4@SiO2@Triazol‐Fc][HCO3] nanoparticles, related
absorption peaks appeared and, especially at about
1700 cm−1, the absorption peak related to the vibration
of the HCO3 group appeared, which confirmed the
successful synthesis of target nanoparticles.
by
(3‐chloropropyl)trimethoxysilane
according
to
reported procedures.[46,47] Then, cycloaddition reaction of
4‐chlorobutylferrocene, propargyl alcohol and sodium
azide afforded (1‐(4‐ferrocenylbutyl)‐1H‐1,2,3‐triazol‐4‐yl)
methanol. Then the reaction of Fe3O4@SiO2‐(CH2)3Cl
with 1,2,3‐triazolylferrocene derivative produced the
[Fe3O4@SiO2@Triazol‐Fc][HCO3] nanocatalyst (Scheme 2).
Chemical analysis of novel [Fe3O4@SiO2@Triazol‐Fc]
[HCO3] nanoparticles was conducted using Fourier
transform infrared (FT‐IR) spectroscopy, X‐ray diffraction
(XRD), energy‐dispersive X‐ray (EDX) analysis, field emis-
sion scanning electron microscopy (FE‐SEM), transmission
electron microscopy (TEM) and Brunauer–Emmett–Teller
(BET) analysis.
The FT‐IR spectra of Fe3O4, Fe3O4@SiO2,
Fe3O4@SiO2@(CH2)3Cl, [Fe3O4@SiO2@Triazol‐Fc][Cl]
and [Fe3O4@SiO2@Triazol‐Fc][HCO3] nanoparticles are
shown in Figure 1. The absorption peaks at about
635 cm−1 are related to Fe&bond;O bond vibrations.
The absorption peaks at about 1079 cm−1 for all
EDX analyses of [Fe3O4@SiO2@Triazol‐Fc][Cl] and
[Fe3O4@SiO2@Triazol‐Fc][HCO3] nanoparticles are pre-
sented in Figure 2. In the EDX spectrum of the newly
synthesized nanocatalyst the expected elements (C, N,
O, Si and Fe) in their regions appeared and showed the
true composition of the nanocatalyst. The absence of Cl
FIGURE 4 (a–c) FE‐SEM images and (d) TEM image of [Fe3O4@SiO2@Triazol‐Fc][HCO3] nanocatalyst

GHOLAMHOSSEINI‐NAZARI ET AL.
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in the EDX spectrum of the final nanocatalyst confirmed
the successful synthesis of nanoparticles.
cos θ), where D is the crystallite size, λ is the X‐ray wave-
length (Cu Kα, 1.54 Å), β is the FWHM of the diffraction
peak and θ is the Bragg diffraction angle in degrees.
The surface morphology and particle size of
[Fe3O4@SiO2@Triazol‐Fc][HCO3] nanoparticles were
evaluated using FE‐SEM analysis (Figure 4a–c). The
FE‐SEM images of the nanocatalyst showed that the
shapes of nanoparticles are spherical with non‐smooth
surfaces which increase the surface‐to‐volume ratio
and cause an improvement in catalytic activity of the
nanoparticles. The [Fe3O4@SiO2@Triazol‐Fc][HCO3]
nanocatalyst was also characterized using TEM and the
results are shown in Figure 4d. The TEM image of the
nanocatalyst confirmed that the shapes of nanoparticles
are spherical. Also the core–shell structure of nanoparti-
cles was observed in the TEM image which demon-
strates the successful synthesis of the nanocatalyst.
According to TEM and FE‐SEM results the particles
are relatively monodisperse and have a uniform size dis-
tribution around 30 nm.
The XRD patterns of [Fe3O4@SiO2@Triazol‐Fc][Cl]
and [Fe3O4@SiO2@Triazol‐Fc][HCO3] nanoparticles
were recorded at 10° to 70°. As shown in Figure 3, the
XRD patterns of nanocatalysts show the crystalline dis-
persions of Fe3O4 magnetic nanoparticles (JCPDS card
no. 85‐1436). The appearance of the same peaks in the
Fe3O4 and [Fe3O4@SiO2@Triazol‐Fc][HCO3] XRD pat-
terns showed that the intended nanoparticles have spinel
structures and, during the functionalization processes,
phase change of Fe3O4 did not occur.
The peak width (full width at half maximum,
FWHM), size and interplanar distance from the
XRD pattern of the [Fe3O4@SiO2@Triazol‐Fc][HCO3]
nanocatalyst were investigated. Crystallite sizes obtained
from several diffraction lines using the Debye–Scherrer
equation were found to be in the nanometre range, which
is mainly in good agreement with the FE‐SEM and TEM
results. For example, measurements for the main diffrac-
tion line, 35.62°, reveal a crystalline size for the catalyst of
28.5 nm using the Debye–Scherrer equation: D = 0.9λ/(β
We investigated the catalytic activity of the newly syn-
thesized [Fe3O4@SiO2@Triazol‐Fc][HCO3] nanocatalyst
TABLE 1 Optimization of solvent and amount of [Fe3O4@SiO2@Triazol‐Fc][HCO3] nanocatalysta
Entry
Catalyst (amount, mg)
Solvent
Time (min)
Yield (%)b
1
—
—
180
120
120
120
120
120
120
120
90
Trace
15
12
12
20
30
15
20
54
30
60
85
96
65
90
2
[BuMeIm][Cl] (10)
[BuMeIm][BF4] (10)
[BuMeIm][PF6] (10)
[BuMeIm][HCO3] (10)
A (10)
—
3
—
4
—
5
—
6
—
7
A (10)
CHCl3
8
A (10)
CH2Cl2
9
A (10)
EtOH
10
11
12
13
14
15
A (10)
H2O
120
60
A (10)
EtOH–H2O (1:1)
EtOH–H2O (2:1)
EtOH–H2O (3:1)
EtOH–H2O (3:1)
EtOH–H2O (3:1)
A (10)
50
A (10)
40
A (5)
60
A (15)
40
aReaction conditions: kojic aldehyde/2‐naphthol/4‐methylaniline (1:1:1.1); catalyst A: [Fe3O4@SiO2@Triazol‐Fc][HCO3].
bIsolated yield.

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GHOLAMHOSSEINI‐NAZARI ET AL.
in the synthesis of kojic acid‐containing Betti bases. Ini-
tially, the reaction of kojic aldehyde (1), 2‐naphthol (2a)
and 4‐methylaniline (3a) was chosen as a model reaction
to optimize the reaction conditions. In this context,
the efficiency of the [Fe3O4@SiO2@Triazol‐Fc][HCO3]
nanocatalyst was investigated in various solvents, at
TABLE 2 Synthesis of 2‐hydroxynaphthalenyl(arylamino)methyl‐4H‐pyran‐4‐one derivatives using 10 mg of [Fe3O4@SiO2@Triazol‐Fc]
[HCO3] nanocatalyst
Entry
Product
Time (min)
Yield (%)
Obs. m.p. (°C)
Lit. m.p. (°C)
1
40
96
134–136
—
2
40
94
145–147
—
3
4
5
45
40
45
90
92
88
138–140
158–160
152–154
—
—
—
(Continues)

GHOLAMHOSSEINI‐NAZARI ET AL.
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TABLE 2 (Continued)
Entry
Product
Time (min)
Yield (%)
Obs. m.p. (°C)
Lit. m.p. (°C)
6
50
86
122–124
123–125[49]
7
8
9
50
45
50
85
92
88
143–145
152–154
185–186
144–146[49]
151–153[49]
184–186[49]
10
50
90
193–195
192–194[49]
various temperatures and with various amounts of
nanocatalyst to obtain a simple, rapid and efficient
procedure for the synthesis of pyran‐bearing Betti bases.
As evident from Table 1, a variety of ionic liquids
were used as catalysts in the model reaction under
solvent‐free conditions, and the results showed that
[Fe3O4@SiO2@Triazol‐Fc][HCO3] is more efficient
than other catalysts. Then a variety of conventional
organic solvents such as CHCl3, CH2Cl2, EtOH and
water were screened for the model reaction in the pres-
ence of 10 mg of nanocatalyst at room temperature.
Interestingly, the best result was achieved when EtOH–
H2O (3:1) was used as solvent in the model reaction
at room temperature (Table 1, entry 13). In continuation,

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GHOLAMHOSSEINI‐NAZARI ET AL.
the model reaction was conducted using various quanti-
ties of nanocatalyst (10, 5 and 15 mg). It was observed
that excellent yield was achieved using 10 mg of
[Fe3O4@SiO2@Triazol‐Fc][HCO3] (Table 1, entry 13)
and further decrease or increase in catalyst quantity did
not increase the yield of the product significantly.
TABLE 3 Synthesis of aryl(pyridinylamino)methyl‐4H‐pyran‐4‐one derivatives using 10 mg of [Fe3O4@SiO2@Triazol‐Fc][HCO3]
nanocatalyst
Entry
Product
Time (min)
Yield (%)
Obs. m.p. (°C)
Lit. m.p. (°C)
1
35
93
181–183
182–184[51]
2
3
35
35
91
92
168–170
173–175
168–170[51]
172–174[51]
4
30
94
174–176
174–176[51]
5
6
30
35
92
87
156–158
160–162
155–157[51]
160–162[51]
(Continues)

GHOLAMHOSSEINI‐NAZARI ET AL.
9 of 15
TABLE 3 (Continued)
Entry
Product
Time (min)
Yield (%)
Obs. m.p. (°C)
Lit. m.p. (°C)
7
30
89
182–184
183–185[51]
8
40
84
161–163
160–162[51]
9
30
90
172–174
173–175[51]
10
30
88
165–167
164–166[51]
To demonstrate the scope and generality of the
method, we designed and synthesized a new class of Betti
bases bearing kojic acid scaffold. For this purpose, the
three‐component condensations of kojic aldehyde (1), 2‐
naphthols (2) and aniline derivatives (3) were investigated
in the presence of the [Fe3O4@SiO2@Triazol‐Fc][HCO3]
nanocatalyst (10 mg) at room temperature. As evident
from Table 2, the reactions were carried out efficiently
within 40–50 min and the corresponding products were
afforded in good to high yields. All compounds were char-
of 2‐naphthol in the traditional Betti reaction. Therefore,
various aldehydes with either electron‐donating or elec-
tron with‐drawing groups were investigated under the
optimized condition. According to the results summarized
in Table 3, the three‐component condensation completed
within 30–40 min with high isolated yields.
The novel synthesized [Fe3O4@SiO2@Triazol‐Fc]
[HCO3] nanocatalyst has several basic and acidic active
sites which could help the promotion of the reaction.
HCO3 is a Brønsted base site of the nanocatalyst which
could activate nucleophiles. Consequently, acidic sites of
the nanocatalyst increase the electrophilicity of the alde-
hydes and activate them to the nucleophilic attack. A
plausible mechanism to explain these three‐component
reactions is presented in Scheme 3. The acid–base inter-
actions among the nanocatalyst, aldehyde and amine lead
1
acterized using FT‐IR, H NMR and 13C NMR spectros-
copies and elemental analysis (C, H and N).
After establishing a general method for the synthesis of
naphthopyran derivatives 4, we tried to synthesize another
important group of pyran‐substituted Betti base derivatives
6 (Table 3). To achieve this aim, kojic acid was used instead

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GHOLAMHOSSEINI‐NAZARI ET AL.
to the efficient reaction of aldehyde and amine deriva-
tives, followed by dehydration and formation of related
imine. In the next step, the catalyst activates 2‐naphthol
or kojic acid and, consequently, nucleophilic attack to
the imine produces the desired products.
Furthermore, the reusability of the catalyst was
investigated with the model reaction under modified
conditions and the results are shown in Figure 5. After
completion of the reaction, the catalyst was separated
using an external magnet. The collected nanocatalyst
was washed several times with EtOH prior to reuse. The
recovered nanocatalyst could be reused for six runs
without significant decrease in activity.
FIGURE 5 Recyclability of [Fe3O4@SiO2@Triazol‐Fc][HCO3]
nanocatalyst in the synthesis of 4a
XRD and FT‐IR analysis of the nanocatalyst after 6
runs of recycling were studied to prove the catalyst stabil-
ity. According to the related data (Figure 6), significant
changes in the nanocatalyst have not been observed after
several uses.
To evaluate the stability of the [Fe3O4@SiO2@Triazol‐
Fc][HCO3] nanocatalyst under acidic conditions, 20 mg of
nanoparticles was dispersed in 50 ml of HCl solution with
a concentration of 0.1 M. After 24 h, the nanocatalyst was
magnetically separated and the leached iron concentra-
tion was determined using atomic emission spectrometry.
This experiment was also repeated for the recycled
[Fe3O4@SiO2@Triazol‐Fc][HCO3] nanocatalyst for com-
parison. The results showed that the leaching of iron from
the nanoparticles was less than 1% which shows the
stability of the nanocatalyst. The measured BET surface
areas for Fe3O4, Fe3O4@SiO2 and [Fe3O4@SiO2@Triazol‐
Fc][HCO3] nanoparticles are 76.4, 72.5 and 53.2 m2 g−1
,
respectively. It is clear that Fe3O4 nanoparticles had the
highest surface area. After coating with a layer of silica,
the surface area slightly decreased and functionalization
of the surface of Fe3O4@SiO2 core–shell nanoparticles
caused a further decrease in surface area to 53.2 m2 g−1
.
The decrease of surface area may be because of an increase
in the size of the particles and their agglomeration.
The magnetization curves measured for Fe3O4,
[Fe3O4@SiO2@Triazol‐Fc][Cl] and [Fe3O4@SiO2@Triazol‐
Fc][HCO3] are compared in Figure 6. The saturation
magnetization value was measured to be 68.0 emu g−1
SCHEME 3 Proposed mechanism for synthesis of products using [Fe3O4@SiO2@Triazol‐Fc][HCO3] nanocatalyst

GHOLAMHOSSEINI‐NAZARI ET AL.
11 of 15
FIGURE 6 XRD and FT‐IR of the nanocatalyst after 6 times use
FIGURE 7 Magnetization curves of (a) Fe3O4, (b) [Fe3O4@SiO2@Triazol‐Fc][Cl] and (c) [Fe3O4@SiO2@Triazol‐Fc][HCO3] nanoparticles
and photographs of magnetic separation of nanocatalyst with an external magnetic field
for Fe3O4. After being coated with silica and subsequent
modifications, the saturated magnetization for
synthesized via three‐component condensation of kojic
aldehyde, 2‐naphthol and aniline derivatives catalysed by
[Fe3O4@SiO2@Triazol‐Fc][HCO3] nanoparticles at room
temperature. Also aryl(pyridinylamino)methyl‐4H‐pyran‐
4‐one derivatives (8a–j) were synthesized using the
novel nanocatalyst via the one‐pot three‐component
condensation reactions of various aromatic aldehydes,
kojic acid and aminopyridine or methylaminopyridine in
EtOH–H2O (3:1) at room temperature. In summary, a
general, efficient and simple operation protocol using a
novel recoverable magnetic nanocatalyst has been
demonstrated to produce pyran‐substituted Betti bases in
short reaction times and good to high yields.
[Fe3O4@SiO2@Triazol‐Fc][Cl] and [Fe3O4@SiO2@Triazol‐
Fc][HCO3] nanoparticles decreased to 28.5 and
26.2 emu g−1, respectively. Although the saturation magne-
tization was reduced for the final nanocatalyst, complete
magnetic separation of [Fe3O4@SiO2@Triazol‐Fc][HCO3]
nanoparticles was achieved using an external magnet.
3 | CONCLUSIONS
A new perspective on the synthesis of pyran‐substituted
Betti base derivatives has been introduced which could
be applied in several fields of synthetic medicinal chem-
istry. In this context, novel [Fe3O4@SiO2@Triazol‐Fc]
[HCO3] nanoparticles were synthesized, characterized
and applied as an efficient heterogeneous catalyst for
the synthesis of a wide variety of pyran‐containing Betti
base derivatives. A series of 2‐hydroxynaphthalenyl(-
arylamino)methyl‐4H‐pyran‐4‐one derivatives (4a–j) were
4 | EXPERIMENTAL
4.1 | Materials and apparatus
All of the chemical reagents used in this project
were purchased from Merck and Sigma‐Aldrich. A MEL‐

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GHOLAMHOSSEINI‐NAZARI ET AL.
TEMP model 1202D apparatus was used for the determi-
nation of melting points. A Bruker Tensor 27 spectrometer
was applied for recording FT‐IR spectra. The 1H NMR and
13C NMR spectra were recorded with a Bruker Spectrospin
Avance 400 spectrometer. A Vario EL III analyser was
applied for the of elementary analyses (C, H, N). XRD pat-
terns of the nanoparticles were obtained with a Siemens
D500 powder X‐ray diffractometer (CuK radiation,
λ = 1.5406 Å). EDX analysis and FE‐SEM were conducted
using a TESCAN MIRA3 field emission scanning electron
microscope. TEM images were recorded with a Zeiss EM
10C electron microscope. BET surface areas of the nano-
particles were determined by N2 adsorption/desorption
with a BELSORP Mini II. Magnetization measurements
were carried out with a model 155 alternative gradient
force magnetometer at room temperature.
Fe3O4@SiO2(CH2)3Cl (1.0 g) in 10 ml of toluene, (1‐(4‐
ferrocenylbutyl)‐1H‐1,2,3‐triazol‐4‐yl)methanol (1.0 g)
was added and the reaction mixture was heated at 80°C
for 72 h. Then, the residue was filtered and washed
with toluene (3 × 20 ml), MeOH (3 × 20 ml) and CH2Cl2
(3 × 20 ml) followed by drying under reduced pressure for
48 h at 40°C to afford the desired [Fe3O4@SiO2@Triazol‐
Fc][Cl] nanoparticles.
4.2.3 | Synthesis of [Fe3O4@SiO2@Triazol‐
Fc][HCO3]
An amount of 0.2 g of sodium bicarbonate was dissolved
in acetone–water (3:1, 40 ml) followed by the addition of
[Fe3O4@SiO2@Triazol‐Fc][Cl] nanoparticles (0.2 g) and
the reaction mixture was placed in an ultrasonic bath
for 15 min. Then, the suspension was stirred using a
mechanical stirrer for 24 h at room temperature. Target
nanoparticles were separated from the reaction mixture
using an external magnet and washed with water, EtOH
and acetone. The desired nanocatalyst was then dried
under vacuum and characterized using FT‐IR spectros-
copy, EDX analysis, XRD, FE‐SEM and TEM.
4.2 | Synthesis of [Fe3O4@SiO2@Triazol‐
Fc][HCO3] nanoparticles
4.2.1 | Synthesis of (1‐(4‐ferrocenylbutyl)‐
1H‐1,2,3‐triazol‐4‐yl)methanol
Propargyl alcohol (5 mmol), 4‐chlorobutylferrocene
(5 mmol) and sodium azide (5.2 mmol) were
introduced in a 25 cm3 round‐bottomed flask in 8 ml od
4.3 | General procedure for synthesis of
2‐hydroxynaphthalenyl(arylamino)methyl‐
4H‐pyran‐4‐one derivatives (4a–j)
dimethylformamide.
A
catalytic amount of CuI
(10 mol%) was then added and the reaction mixture was
heated to 80°C for 12 h. The progress of the reaction
was monitored by TLC until total conversion of the
starting materials. After completion of the reaction, the
product was extracted with EtOAc. The combined organic
layers were dried over anhydrous Na2SO4, filtered and
the solvent evaporated to afford the corresponding
ferrocenyltriazole derivative. The residue was purified
with silica column chromatography (n‐hexane–ethyl ace-
tate, 9:1, as eluent) to produce (1‐(4‐ferrocenylbutyl)‐1H‐
1,2,3‐triazol‐4‐yl)methanol. FT‐IR (cm−1): 3324, 3122,
To a mixture of kojic aldehyde (1 mmol), 2‐naphthol or 6‐
bromo‐2‐naphthol (1 mmol) and aniline derivative
(1.1 mmol) in 4 ml of EtOH–H2O (3:1) was added
[Fe3O4@SiO2@Triazol‐Fc][HCO3] nanocatalyst (10 mg).
The mixture was stirred at room temperature and the
progress of the reaction was monitored by TLC (EtOAc–
n‐hexane, 1:4). After completion of the reaction, the
catalyst was separated using an external magnet and the
precipitate was collected by filtration and purified by
recrystallization from EtOH. The separated nanocatalyst
was washed with EtOH several times and dried for
subsequent uses. The structures of newly synthesized
compounds were characterized using FT‐IR, 1H NMR
and 13C NMR spectroscopies and CHN analysis.
1
2945, 2884, 1663, 1631, 1547. H NMR (δ, ppm): 1.57–
1.61 (m, 2H, &bond;CH2&bond;), 1.66–1.73 (m, 2H,
&bond;CH2&bond;), 2.34 (t, J = 7.5 Hz, 2H, &bond;
CH2&bond;), 4.09–4.15 (m, 9H, CpH), 4.15–4.19 (m, 2H,
&bond;CH2&bond;), 4.62 (s, 2H, &bond;CH2OH), 5.26
(bs, 1H, &bond;OH), 8.06 (s, 1H, triazole&bond;H). 13C
NMR (δ, ppm): 26.0, 27.0, 27.8, 55.7, 62.5, 66.0, 66.9,
67.4, 87.4, 128.7, 149.8.
4.4 | General procedure for synthesis of
aryl(pyridinylamino)methyl‐4H‐pyran‐4‐
one derivatives (8a–j)
4.2.2 | Synthesis of [Fe3O4@SiO2@Triazol‐
Fc][Cl]
To a mixture of kojic acid (1 mmol), aldehyde derivative
(1 mmol) and aminopyridine or methylaminopyridine
(1.1 mmol) in 4 ml of EtOH–H2O (3:1) was added
[Fe3O4@SiO2@Triazol‐Fc][HCO3] nanocatalyst (10 mg).
Fe3O4@SiO2‐propylchloride was prepared according
to reported procedures.[46,47] Then, to a mixture of

GHOLAMHOSSEINI‐NAZARI ET AL.
13 of 15
The mixture was stirred at room temperature and the
progress of the reaction was monitored by TLC (EtOAc–
n‐hexane, 2:1). After completion of the reaction, the
catalyst was separated using an external magnet and the
precipitate was collected by filtration and purified by
recrystallization from EtOH. The separated nanocatalyst
was washed with EtOH several times and dried for subse-
quent uses.
4.5.3 | 5‐(Benzyloxy)‐2‐[((3‐chlorophenyl)
amino)(2‐hydroxynaphthalen‐1‐yl)methyl]‐
4H‐pyran‐4‐one (4c)
Pale yellow solid; m.p. 138–140°C. FT‐IR (KBr, cm−1):
3351, 3298, 3045, 2984, 1632, 1546, 1219. 1H NMR
(400 MHz, CDCl3, δ, ppm): 4.98 (2H, 2 × d, J = 12.0 Hz,
benzylic‐H), 5.74 (1H, s, NH), 6.29 (1H, s, methine‐H),
6.55–6.57 (1H, m, Ar‐H), 6.70–6.78 (2H, s, Ar‐H), 6.86
(1H, d, J = 8.8 Hz, Ar‐H), 7.08–7.13 (1H, m, Ar‐H),
7.29–7.37 (7H, m, Ar‐H), 7.50–7.57 (2H, m, Ar‐H), 7.61–
7.64 (1H, m, Ar‐H), 7.79–7.81 (1H, m, Ar‐H), 8.05–8.07
(1H, m, Ar‐H), 10.43 (1H, bs, OH). 13C NMR (100 MHz,
CDCl3, δ, ppm): 53.5, 71.9, 112.0, 112.3, 113.2, 113.7,
118.7, 119.1, 121.5, 123.2, 127.4, 127.6, 128.6, 128.8,
128.9, 129.2, 130.5, 130.9, 132.2, 135.2, 135.3, 141.7,
146.9, 147.7, 154.2, 169.2, 176.1. Anal. Calcd for
C29H22ClNO4 (%): C, 71.97; H, 4.58; N, 2.89. Found (%):
C, 71.73; H, 4.60; N, 2.86.
4.5 | Characterization data
4.5.1 | 5‐(Benzyloxy)‐2‐((2‐
hydroxynaphthalen‐1‐yl)(p‐tolylamino)
methyl)‐4H‐pyran‐4‐one (4a)
Pale yellow solid; m.p. 134–136°C. FT‐IR (KBr, cm−1):
1
3375, 3334, 3051, 2955, 1639, 1579, 1514, 1203. H NMR
(400 MHz, CDCl3, δ, ppm): 2.26 (3H, s, CH3), 4.98 (2H,
2 × d, J = 12.4 Hz, benzylic‐H), 5.12 (1H, s, NH), 6.21
(1H, s, methine‐H), 6.67–6.70 (3H, m, Ar‐H), 6.98 (2H,
d, J = 8.4 Hz, Ar‐H), 7.23–7.25 (1H, m, Ar‐H), 7.29–7.41
(6H, m, Ar‐H), 7.51–7.55 (2H, m, Ar‐H), 7.68 (1H, d,
J = 8.8 Hz, Ar‐H), 7.81 (1H, d, J = 8.0 Hz, Ar‐H), 7.97
(1H, d, J = 8.8 Hz, Ar‐H), 10.61 (1H, bs, OH). 13C NMR
(100 MHz, CDCl3, δ, ppm): 20.5, 55.7, 71.8, 112.7, 113.3,
115.1, 119.5, 121.3, 121.4, 123.1, 127.3, 127.7, 127.8,
128.5, 128.8, 128.9, 129.2, 129.6, 129.9, 130.1, 130.9,
132.1, 135.5, 141.4, 143.7, 147.0, 155.2, 167.7, 175.5. Anal.
Calcd for C30H25NO4 (%): C, 77.74; H, 5.44; N, 3.02.
Found (%): C, 77.51; H, 5.46; N, 3.00.
4.5.4 | 5‐(Benzyloxy)‐2‐[((5‐chloro‐2‐
iodophenyl)amino)(2‐hydroxynaphthalen‐
1‐yl)methyl]‐4H‐pyran‐4‐one (4d)
Pale yellow solid; m.p. 158–160°C. FT‐IR (KBr, cm−1):
1
3345, 3278, 3063, 2874, 1637, 1577, 1505, 1208. H NMR
(400 MHz, CDCl3, δ, ppm): 4.99 (2H, 2d, J = 12.2 Hz,
benzylic‐H), 6.27 (1H, d, J = 6.9 Hz, methine‐H), 6.47–
6.49 (1H, m, Ar‐H), 6.57 (1H, s, pyrone‐H), 6.67 (1H, s,
N‐H), 7.03 (1H, s, Ar‐H), 7.28–7.36 (7H, m, Ar‐H), 7.46
(1H, d, J = 8.2 Hz, Ar‐H), 7.52–7.60 (3H, m, Ar‐H,
pyrone‐H), 7.74 (1H, d, J = 8.1 Hz, Ar‐H), 8.10 (1H, d,
J = 8.7 Hz, Ar‐H), 10.81 (1H, s, OH). 13C NMR
(100 MHz, CDCl3, δ, ppm): 52.1, 82.5, 70.9, 109.4, 110.7,
112.6, 117.9, 118.3, 120.6, 122.0, 126.3, 126.6, 127.5,
127.7, 127.9, 128.2, 129.9, 131.1, 134.3, 134.4, 138.9,
140.8, 145.9, 145.9, 152.9, 168.1, 175.4. Anal. Calcd for
C29H21ClINO4 (%): C, 57.12; H, 3.47; N, 2.30. Found (%):
C, 56.88; H, 3.48; N, 2.31.
4.5.2 | 5‐(Benzyloxy)‐2‐[((4‐chlorophenyl)
amino)(2‐hydroxynaphthalen‐1‐yl)methyl]‐
4H‐pyran‐4‐one (4b)
Pale yellow solid; m.p. 145–147°C. FT‐IR (KBr, cm−1):
1
3361, 3342, 3049, 2928, 1633, 1608, 1516, 1218. H NMR
(400 MHz, CDCl3, δ, ppm): 5.01 (2H, 2 × d, J = 12.0 Hz,
benzylic‐H), 5.58 (1H, s, NH), 6.22 (1H, s, methine‐H),
6.62 (2H, d, J = 8.8 Hz, Ar‐H), 6.77 (1H, s, Ar‐H), 7.12
(2H, d, J = 8.8 Hz, Ar‐H), 7.26–7.29 (1H, m, Ar‐H),
7.32–7.38 (6H, m, Ar‐H), 7.52–7.58 (2H, m, Ar‐H), 7.63
(1H, d, J = 8.8 Hz, Ar‐H), 7.80 (1H, d, J = 8.0 Hz, Ar‐
H), 8.01 (1H, d, J = 8.8 Hz, Ar‐H), 10.43 (1H, bs, OH).
13C NMR (100 MHz, CDCl3, δ, ppm): 54.4, 71.8, 112.6,
113.2, 115.3, 119.2, 121.3, 123.2, 124.0, 127.4, 127.6,
128.6, 128.8, 128.9, 129.2, 129.3, 130.9, 132.1, 135.3,
141.6, 144.9, 146.9, 154.4, 168.5, 175.9. Anal. Calcd for
C29H22ClNO4 (%): C, 71.97; H, 4.58; N, 2.89. Found (%):
C, 71.71; H, 4.59; N, 2.85.
4.5.5 | 5‐(Benzyloxy)‐2‐((6‐bromo‐2‐
hydroxynaphthalen‐1‐yl)((2‐bromophenyl)
amino)methyl)‐4H‐pyran‐4‐one (4e)
Pale yellow solid; m.p. 152–154°C. FT‐IR (KBr, cm−1):
1
3389, 3342, 3066, 2925, 1637, 1576, 1499, 1206. H NMR
(400 MHz, CDCl3, δ, ppm):4.92 (2H, 2d, J = 12.4 Hz,
benzylic‐H), 6.22 (2H, s, methine‐H, N&bond;H), 6.55–
6.59 (2H, m, Ar‐H), 6.78 (1H, s, pyrone‐H), 7.05 (1H, t,
J = 7.8 Hz, Ar‐H), 7.20–7.31 (7H, m, Ar‐H), 7.36 (1H, d,
J = 8.8 Hz, Ar‐H), 7.47 (1H, dd, J = 9.1 Hz, J = 1.5 Hz,
Ar‐H), 7.51 (1H, s, pyrone‐H), 7.79 (1H, d, J = 1.5 Hz,

14 of 15
GHOLAMHOSSEINI‐NAZARI ET AL.
[20] A. Shahrisa, R. Teimuri‐Mofrad, M. Gholamhosseini‐Nazari,
Synlett 2015, 26, 1031.
Ar‐H), 7.88 (1H, d, J = 9.1 Hz, Ar‐H), 10.63 (1H, s, OH).
13C NMR (100 MHz, CDCl3, δ, ppm): 52.3, 70.9, 110.0,
110.9, 111.1, 113.1, 115.5, 118.3, 119.1, 122.4, 126.6,
127.5, 127.7, 128.8, 129.1, 129.3, 129.7, 130.0, 131.8,
134.3, 140.8, 142.3, 145.9, 153.4, 167.7, 175.1. Anal. Calcd
for C29H21Br2NO4 (%): C, 57.36; H, 3.49; N, 2.31. Found
(%): C, 57.11; H, 3.51; N, 2.30.
[21] C. Cardellicchio, M. A. M. Capozzi, F. Naso, Tetrahedron:
Asymmetry 2010, 21, 507.
[22] I. Szatmári, F. Fülöp, Tetrahedron 2013, 69, 1255.
[23] A. Kumar, M. K. Gupta, M. Kumar, Tetrahedron Lett. 2010, 51,
1582.
[24] B. Karmakar, J. A. Banerji, Tetrahedron Lett. 2011, 52, 4957.
[25] S. D. Dindulkar, V. G. Puranik, Y. T. Jeong, Tetrahedron Lett.
2012, 53, 4376.
ACKNOWLEDGEMENTS
The authors acknowledge financial support from the Iran
National Science Foundation (INSF) and the University
of Tabriz.
[26] K. M. Khandarkar, M. D. Shanti, M. Ahmed, J. S. Meshram,
J. Chem. Sci. 2013, 125, 1573.
[27] N. Gyémánt, H. Eng, Z. Schelz, I. Szatmári, D. Tóth, F. Fülöp,
J. Molnár, P. De Witte, Br. J. Cancer 2010, 103, 178.
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ORCID
877.
Kazem D. Safa https://orcid.org/0000-0003-4550-9751
[29] I. Szatmári, A. Hetényi, L. Lázár, F. Fülöp, J. Heterocycl. Chem.
2004, 41, 367.
Reza Teimuri‐Mofrad
https://orcid.org/0000-0002-5812-
6445
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How to cite this article: Gholamhosseini‐Nazari
M, Esmati S, Safa KD, Khataee A, Teimuri‐Mofrad
R. Synthesis and application of novel 1,2,3‐
triazolylferrocene‐containing ionic liquid
supported on Fe3O4 nanocatalyst in the synthesis of
new pyran‐substituted Betti bases. Appl
Organometal Chem. 2019;e4701. https://doi.org/
10.1002/aoc.4701
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