Synthesis of 1-aminoalkyl-2-naphthols derivatives using an engineered copper-based nanomagnetic catalyst (Fe3O4@CQD@Si (OEt)(CH2)3NH@CC@N3@phenylacetylene@Cu)

Article abstract of DOI:10.1002/aoc.6361

In the present study, a molecular level engineered-based method was used to synthesis a copper-based nanomagnetic catalyst (Fe₃O₄@CQD@Si (OEt)(CH₂)₃NH@CC@N₃@phenylacetylene@Cu). The as-synthesized cat

Full text of DOI:10.1002/aoc.6361

Received: 22 October 2020
DOI: 10.1002/aoc.6361
Revised: 22 May 2021
Accepted: 29 May 2021
F U L L P A P E R
Synthesis of 1-aminoalkyl-2-naphthols derivatives using
an engineered copper-based nanomagnetic catalyst
(Fe3O4@CQD@Si (OEt)(CH2)3NH@CC@N3
@phenylacetylene@Cu)
Tahereh Akbarpour1
Negin Sarmasti1
| Ardeshir Khazaei1
| Jaber Yousefi Seyf2
|
1Faculty of Chemistry, Bu-Ali Sina
University, Hamedan, Iran
Abstract
2Department of Chemical Engineering,
Hamedan University of Technology,
Hamedan, Iran
In the present study, a molecular level engineered-based method was used to
synthesis a copper-based nanomagnetic catalyst (Fe3O4@CQD@Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu). The as-synthesized catalyst was
characterized using different techniques, including infrared (IR), X-ray powder
diffraction (XRD), field emission scanning electron microscopy (FESEM) and
transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy
(EDX) and EDX elemental mapping, induced coupled plasma (ICP), thermal
gravimetric analysis (TGA) and differential thermal analysis (DTA), and
vibrating sample magnetometer (VSM). The Fe3O4 nanoparticles surface were
protected using carbon quantum dots (CQDs) instead of conventional SiO2.
The activity of the as-synthesized catalyst was evaluated in the synthesis of
1-aminoalkyl-2-naphthols derivatives. The solvent-free condition with low
reaction time and high reaction yield is the results of the prepared catalyst.
How the reaction was triggered by the catalyst was determined by the IR. The
as-synthesized catalyst provides an 87.5% reaction yield after five cycles.
Fourier Transform Infrared (FTIR), EDX, TEM, TGA, and mapping analyses
were taken to examine the stability of the recovered catalyst. All elements,
especially Cu with 2.4 wt%, are present in the recovered catalyst. These
findings provide strong evidence for the stability of the as-synthesized novel
copper-based heterogeneous magnetic nanocatalyst. The effect of temperature
and the amount of the catalyst (optimum reaction condition) were determined
using a systematic approach, namely, the design of experiment (DOE).
Correspondence
Ardeshir Khazaei, Professor, Faculty of
Chemistry, Bu-Ali Sina University,
Hamedan, Iran.
Email: a_khazaei@basu.ac.ir
K E Y W O R D S
1-aminoalkyl-2-naphthols, copper-based catalyst, design of experiment (DOE)
Appl Organomet Chem. 2021;e6361.
wileyonlinelibrary.com/journal/aoc
© 2021 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.6361

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AKBARPOUR ET AL.
1 | INTRODUCTION
(CQDs) instead of conventional SiO2.[40] The major objec-
tive of this study is to synthesize a novel copper-based
heterogeneous magnetic nanocatalyst and its usage in the
synthesis of 1-(α-aminoalkyl)-2-naphthols derivatives.
The multicomponent reactions (MCRs) have proven a
valuable asset in organic and pharmaceutical chemistry.
MCRs can be used in drug design and discovery because of
the simplicity, efficiency, and high selectivity of the
MCRs.[1] The synthesis of biologically complex molecules,
besides the minimum workup procedure, by MCRs, is
easy, fast, and efficient.[2] Nitrogen-containing biologically
active compounds as a significant branch of organic syn-
thesis are medically important.[3–5] Since 1900, aminoalkyl
naphthols have been synthesized by the three-component
condensation of secondary amines, aromatic aldehydes,
and naphthols.[6] In 1900, Mario Betti synthesized
aminoalkyl naphthols (so-called Betti bases) for the first
time.[7] Interest in the chemistry of Betti base[8] has
recently intensified because of their attractive catalytic[9]
and biological[8] properties. The Betti reaction is useful in
the synthesis of substituted aminonaphthols. Compounds
such as 1-(α-aminoalkyl)-2-naphthols are often found in
naturally occurring biologically active products and potent
drugs, such as nucleoside antibiotics and HIV proteinase
inhibitors.[10–13] These compounds are also important pre-
cursors in the synthesis of compounds that are often used
in biologically important natural products and drugs.[12]
Several catalysts have been applied to synthesize of 1-(α-
aminoalkyl)-2-naphthols derivatives, including deep eutec-
tic solvent (DES),[14] glycerol,[15] Triton X-100 in H2O,[16]
Fe3O4 magnetic nanoparticles (MNPs),[17] microwave
irradiation,[18] nano TiO2-HClO4,[19] and ionic liquid.[20]
In recent years, nanomaterials have been used as a
solid support material for the design of benign environ-
2 | EXPERIMENTAL SECTION
2.1 | Material and methods
FeCl2.4H2O, FeCl3.6H2O, ammonia (28%wt), glucose,
3-(trimethoxysilyl)-propylamine
(TMPA),
toluene
(anhydrous), cyanuric chloride, tetrahydrofuran (THF),
NaN3, K2CO3, acetone, phenylacetylene, NaOH, CH3CN,
Cu (OAc)2, and MeOH all were purchased from Merck
company.
The FTIR spectra (Perkin-Elmer 1600 spectrometer
using KBr disks), field emission scanning electron
microscopy (FESEM), transmission electron microscopy
(TEM), energy-dispersive X-ray analysis (EDXA), thermal
gravimetric analysis (TGA), and vibrating sample magne-
tometer (VSM) were used in the characterization of the
as-synthesized catalyst.
Beta-naphthol, benzaldehyde derivatives, and
secondary amines (morpholine and piperidine) were used
in the synthesis of 1-aminoalkyl-2-naphthols derivatives.
Products were characterized using melting point, FTIR,
1H NMR, and 13C NMR techniques.
2.1.1 | Preparation of Fe3O4 nanoparticles[41]
mental heterogeneous catalysts.[21–23]
A
variety of
Fe3O4 nanoparticles were synthesized using the
co-precipitation method. First, FeCl3.6H2O (15.2 gr,
56.34 mmol) and FeCl2.4H2O (5.6 gr, 28.17 mmol) were
dissolved in deionized H2O at 80ꢀC. After the dissolution
of both salts, ammonia (25 ml, 28%wt) was added to the
solution at once. The obtained black suspension was
vigorously stirred at 80ꢀC for 2 h under a nitrogen
atmosphere. The synthesized Fe3O4 nanoparticles were
separated using an external magnet. Nanoparticles
were dried in an oven after washing several times with
H2O and acetone.
methods have been developed to synthesize magnetite
nanoparticles of various shapes, sizes, and compositions,
but their successful applications are highly dependent on
the stability conditions of these particles.[24,25] MNPs have
a high affinity to agglomeration, and therefore, suitable
protective materials have been investigated for their
stabilization.[26–34] Surfactant/polymer, silica, and carbon-
coating or embedding them in a matrix/support are some
of the critical approaches adopted to stabilize nanostruc-
tured particles.[35,36] It is noteworthy to note that the outer
protective shells created as a result of the coating not only
stabilize nanoparticles but also provide interaction sites
with other synthetic atoms, nanoparticles, and organic
groups suitable for their intended applications. Recently,
the focus has been on the functionality of MNPs to expand
their application, especially in the field of catalysis, as
evidenced by the use of MNPs for the manufacture of
magnetite-based catalysts.[37–39]
2.1.2 | Preparation of CQD by glucose[29,42]
Glucose (10 gr, 55.5 mmol) was added to the hot edible
oil (250ꢀC) and heated until completely blackened. H2O
(50 ml) and diethyl ether (20 ml) were added to the solu-
tion after cooling. The extraction procedure was repeated
three times so that all the synthesized CQDs enter the
aqueous phase and the oil enters the organic phase.
In light of these, this study intends to coat the surface
of Fe3O4 nanoparticles using carbon quantum dots

AKBARPOUR ET AL.
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2.1.3 | Preparation of nano-Fe3O4@CQD
solution composed of H2O (40 ml) and acetone (20 ml)
and was dispersed for 15 min using an ultrasonic bath
(mixture A). Mixture A was added to mixture B and
was stirred at room temperature for 6 h. The
obtained Fe3O4@CQD@ Si (OEt)(CH2)3NH@CC@N3
nanoparticles were separated using an external magnet
and then were dried in an oven after washing with H2O
and acetone. To confirm the nucleophilic substitution of
Clꢁ by Nꢁ3 , Fe3O4@CQD@Si (OEt)(CH2)3NH@CC@N3
was burned in a porcelain crucible and its ash was dis-
solved in acid. Then, AgNO3(aq) was added to the solution
so that the failure to observe AgCl precipitation is a
reason for the nucleophilic substitution of Clꢁ by N3ꢁ.
Of the previous step synthesized Fe3O4 nanoparticles,
1 gr was dispersed in deionized H2O (50 ml) using an
ultrasonic bath for 30 min. Then, CQDs (0.05 gr) were
added to the dispersion and were stirred for 24 h at room
temperature. CQDs are dissolved in water in a molecular-
like form so that a low amount of CQDs can cover
1000 mg of nano-Fe3O4 (in particle form). The obtained
nano-Fe3O4@CQD nanoparticles were separated using
an external magnet and were dried in an oven after wash-
ing with deionized H2O. The used CQDs (50 mg) is
excess so that after the separation of nano-Fe3O4@CQD
nanoparticles, the solution also contains CQDs
(brown solution).
2.1.7 | Preparation of Fe3O4@CQD@Si
(OEt)(CH2)3NH@CC@N3@phenylacetylene[46]
2.1.4 | Surface modification of
Fe3O4@CQD@ Si (OEt)(CH2)3NH2
[43]
Of the Fe3O4@CQD@ Si (OEt)(CH2)3NH@CC@N3
nanoparticles, 1 gr was dispersed in CH3CN using
an ultrasonic bath. Then phenylacetylene (2.5 ml)
and NaOH (0.5%w/v) were added to the dispersion,
and it was stirred at room temperature for 6 h.
The obtained Fe3O4@CQD@Si (OEt)(CH2)3NH@CC@N3
@phenylacetylene nanoparticles were separated using an
external magnet and then were dried in an oven after
washing with CH3CN and H2O.
Of the previous step synthesized nano-Fe3O4@CQD
nanoparticles, 2 gr was dispersed in toluene using an
ultrasonic bath for 25 min. The previous step was carried
out multiple times and does not violate the mass conser-
vation of law. TMPA (2 ml) was added to the dispersion
and was refluxed under a nitrogen atmosphere for 24 h
(at 110–120ꢀC). The obtained Fe3O4@CQD@ Si (OEt)
(CH2)3NH2 nanoparticles were separated using an exter-
nal magnet and were dried in an oven after washing with
toluene and H2O.
2.1.8 | Fe3O4@CQD@Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@cu[47]
2.1.5 | Preparation of Fe3O4@CQD@Si
(OEt)(CH2)3NH@CC[44]
First, a 5% (w/v) solution of Cu (OAc)2 was prepared in
MeOH (solution A). About 1 gr Fe3O4@CQD@Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene nanoparticles was
dispersed in MeOH (50 ml) using an ultrasonic bath for
15 min (dispersion B). Then the solution A was added
to the dispersion B dropwise. After refluxing the
dispersion for 24 h, the obtained Fe3O4@CQD@Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu
nanoparticles were separated using an external
magnet and were dried in an oven after washing several
times with MeOH. This is the final experimental step
in the preparation of a heterogeneous copper-based
Cyanuric chloride (CC, 2.76 gr, 15 mmol) was dissolved
in THF (30 ml) at a nitrogen atmosphere (at 0ꢀC for 3 h).
Of the Fe3O4@CQD@Si (OEt)(CH2)3NH2 nanoparticles,
1 gr was added to the solution and dispersed
using an ultrasonic bath for 30 min then was stirred
at 0ꢀC for 24 h. The obtained Fe3O4@CQD@Si (OEt)
(CH2)3NH2@CC nanoparticles were separated using an
external magnet and were dried in an oven after washing
with EtOH and THF.
nanomagnetic catalyst. Scheme
1
illustrates the
conceptual procedure synthesis of copper-based
nanomagnetic catalyst, namely, Fe3O4@CQD@Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu.
2.1.6 | Preparation of Fe3O4@CQD@ Si
(OEt)(CH2)3NH@CC@N3
[45]
To further study the structure of the formed catalyst,
density functional theory (DFT) calculation was per-
formed using DMol3 module of the material studio soft-
ware. The CC@N3@phenylacetylene parts of the catalyst
were studied in the DFT calculation to find the parts of
Sodium azide (1.56, 24 mmol) together with K2CO3
(1.66 gr, 12 mmol) as a base were dissolved in 20-ml
deionized H2O (mixture A). Of the Fe3O4@CQD@Si
(OEt)(CH2)3NH2@CC nanoparticles, 1 gr was added to a

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AKBARPOUR ET AL.
FIGURE 1 The proposed structure for the as-synthesized
catalyst. Electron density was determined using density function
theory (DFT)
SCHEME 1 The proposed procedure for the synthesis of
copper-based nanomagnetic catalyst, namely, Fe3O4@CQD@Si
(OEt)(CH2)3NH@CC@N3@phenylacetylene@Cu
SCHEME 2 The synthesis of 1-aminoalkyl-2-naphthols
derivatives in the presence of the as-synthesized copper-based
nanomagnetic catalyst
CC@N3@phenylacetylene
with
higher
electron
density. Figure 1 displays the electron density of
CC@N3@phenylacetylene. As is shown, nitrogen atoms
have higher electron density so that the proposed struc-
ture is entropically favorable and it is easier to coordinate
copper with two rings.
130 solvents for the crystallization operation. The solvent
of crystallization was obtained by this method. Scheme 2
presents the conceptual synthesis procedure of the
1-aminoalkyl-2-naphthols derivatives in the presence of
the as-synthesized copper-based nanomagnetic catalyst.
2.2 | General procedure for the synthesis
of 1-aminoalkyl-2-naphthols derivatives
3 | RESULTS AND DISCUSSION
3.1 | Characterization of the catalyst
β-naphthol (0.144 gr, 1 mmol), aryl aldehyde (1 mmol),
and secondary amine including morpholine or piperidine
(1 mmol) together with 0.05 gr of the as-synthesized cata-
lyst were added to a test tube. Then the mixture was
stirred at the obtained optimal condition, including
0.05-gr catalyst at 104ꢀC. The reaction procedure was
monitored using thin-layer chromatography (TLC). Hot
EtOH (20 ml) was added to the reaction mixture after the
completion of the reaction. The heterogeneous catalyst
was separated from the reaction mixture using an
external magnet, and the pure products were obtained
through recrystallization in EtOH. Haghtalab and
Yousefi Seyf[48] and Yousefi Seyf and Asgari[49] have
extended the UNIQUAC-SAC model to fast screening
Various techniques including infrared (IR) spectroscopy,
X-ray powder diffraction (XRD), FESEM, TEM, induced
coupled plasma (ICP), EDXA, energy-dispersive X-ray
spectroscopy (EDX) elemental mapping, TGA, and VSM
were used to characterize the as-synthesized catalyst.
3.1.1 | Infrared
IR technique was used to identify different functional
groups in the as-synthesized nanoparticles qualitatively.

AKBARPOUR ET AL.
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Figure 2 presents the (Fourier Transform Infrared) FTIR
spectra of the Fe3O4, Fe3O4@CQD, Fe3O4@CQD@ Si
(OEt)(CH2)3NH2, Fe3O4@CQD@Si (OEt)(CH2)3NH@CC,
Fe3O4@CQD@ Si (OEt)(CH2)3NH@CC@N3, Fe3O4
@CQD@Si (OEt)(CH2)3NH@CC@N3@phenylacetylene,
triazole ring (brown spectrum). However, accentuations
and small frequency shifts are observed in the cyan IR
spectrum; Cu-N peaks at 592 and 693 cmꢁ1 confirm the
dative bond formation between copper and nitrogen
atoms.[33,47,50]
and
Fe3O4@CQD@
Si
(OEt)(CH2)3NH@CC@N3
@phenylacetylene@Cu. The wave numbers of 584 and
3396 cmꢁ1 are attributed to the Fe-O bending and Fe-O
stretching, respectively (red spectrum). The wave num-
bers of 1619 and 3296 cmꢁ1 are attributed to the carbonyl
and hydroxyl groups in CQD, respectively (green spec-
trum). The wave numbers of 1034, 2922, and 3454 cmꢁ1
belong to the Si-O, C-H stretching and NH2 stretching in
the Fe3O4@CQD@Si (OEt)(CH2)3NH2 nanoparticles
(blue spectrum). The band at 1654 cmꢁ1 is an indication
of the presence of the C=N functional group in cyanuric
chloride that proves the formation of Fe3O4@CQD@Si
(OEt)(CH2)3NH@CC nanoparticles (magenta spectrum).
The wave numbers of 2036 and 2136 cmꢁ1 confirm the
formation Fe3O4@CQD@Si (OEt)(CH2)3NH@CC@N3
nanoparticles with azide functional group (black
spectrum). The reaction between the azide group and
phenylacetylene gives rise to the formation of a pentago-
nal triazole ring so that the azide wave number disap-
pears. The emergence of a band at 1560 and 1620 cmꢁ1
implies to the presence of C=N and N=N groups in the
3.1.2 | X-ray powder diffraction
The resultants nanoparticles were then characterized by
XRD technique. The powder diffraction patterns are
given in Figure 3. Observed sharp peaks prove the
crystallize nature of the nanoparticles. The sharper the
diffraction peaks, the bigger the nanoparticle size.
3.1.3 | Field emission scanning electron
microscopy and transmission
electron microscopy
(Scanning electron microscope) SEM analysis is one of
the most widely used analyses of the surface
of nanocatalysts. Using this method, the microstructure
of materials can be examined by the electron beam in
surface scanning. The most important feature of scanning
electron microscopy is the three-dimensional display of
FIGURE 2 Infrared (IR) spectra of Fe3O4, Fe3O4@CQD, Fe3O4@CQD@Si (OEt)(CH2)3NH2, Fe3O4@CQD@Si (OEt)(CH2)3NH@CC,
Fe3O4@CQD@Si (OEt)(CH2)3NH@CC@N3, Fe3O4@CQD@Si (OEt)(CH2)3NH@CC@N3@phenylacetylene, and Fe3O4@CQD@ Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu

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AKBARPOUR ET AL.
FIGURE 3 X-ray
diffractograms of the
as-synthesized nanoparticles
FIGURE 4 The field emission scanning electron microscopy (FESEM) image of the as-synthesized heterogeneous copper base magnetic
nanocatalyst, namely, Fe3O4@CQD@ Si (OEt)(CH2)3NH@CC@N3@phenylacetylene@Cu
images due to its great depth of field. This technique
is used to determine the shape, size, and morphology
of the nanoparticle surface. The FESEM images of
the as-synthesized heterogeneous copper base magnetic
nanocatalyst are shown in Figure 4. As is shown in this
figure, the obtained nanocatalyst is spherical.
nanoparticles. The gray background between the
nanoparticles is attributed to the CQDs.
3.1.4 | EDX and EDX elemental mapping
To further investigate the structure of the as-
synthesized copper-based magnetic nanocatalyst, the
TEM technique was used. Figure 5. provides the detailed
structure of the as-synthesized nanoparticles. The TEM
image of the as-synthesized catalyst shows a layer
anchoring around the core of the Fe3O4 nanoparticle,
confirming the core-shell structure of the as-synthesized
The EDX technique is used to determine the elemental
analysis of a sample. The EDX analysis of the as-
synthesized copper-based magnetic nanocatalyst is
shown in Figure 6. This figure confirms the presence of
the Fe, O, C, Si, N, and Cu elements in the final as-
prepared catalyst. The mass percent of the Fe, O, C, Si, N,
and Cu elements is 29.35, 24.62, 8.50, 0.90, 2.25, and

AKBARPOUR ET AL.
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FIGURE 5 Transmission electron microscopy (TEM) micrographs of the as-synthesized heterogeneous copper base magnetic
nanocatalyst, namely, Fe3O4@CQD@ Si (OEt)(CH2)3NH@CC@N3@phenylacetylene@Cu
34.37, respectively. Based on the ICP technique, besides,
the mass percent of obtained copper is equal to 21.64%.
These findings confirm the presence of copper in the as-
synthesized catalyst so that 5.4 mmol copper is loaded
per gram of the catalyst (5.4 mmol Cu/g catalyst). To
prove the presence of different elements in the as-
synthesized catalyst structure, the EDX elemental
mapping was taken (Figure 7). As shown in this figure,
carbon, copper, iron, nitrogen, oxygen, and silicon form
the elemental composition of the catalyst.
3.1.5 | Thermal gravimetric analysis and
differential thermal analysis
TGA and differential thermal analysis (DTA) were used
to evaluate the thermal stability of the as-synthesized
catalyst. TAG and DTA of the copper-based magnetic
nanocatalyst are shown in Figure 8. Weight loss before
FIGURE 6 The energy-dispersive X-ray spectroscopy (EDX) of
the as-synthesized catalyst, namely, Fe3O4@CQD@ Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu

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AKBARPOUR ET AL.
FIGURE 7 Energy-dispersive X-ray spectroscopy (EDX) elemental mapping of the as-synthesized catalyst, namely, Fe3O4@CQD@ Si
(OEt)(CH2)3NH@CC@N3@phenylacetylene@Cu
FIGURE 8 Thermal gravimetric analysis
(TGA) and differential thermal analysis (DTA)
of the as-synthesized catalyst, namely,
Fe3O4@CQD@Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu
FIGURE 9 Magnetization curves of the
Fe3O4, and the as-synthesized catalyst, namely
Fe3O4@CQD@ Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu
catalyst

AKBARPOUR ET AL.
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100ꢀC is attributed to the H2O and solvents trapped in
the as-synthesized catalyst structure (A). Drops in regions
B to F are related to different layers loaded on the synthe-
sized catalyst. As is shown in this figure, the as-prepared
catalyst is stable at high temperatures, especially up to
700ꢀC (this catalyst losses only 20%wt of its mass).
3.1.6 | Vibrating sample magnetometer
This technique is used to identify the magnetic properties
of a material. The magnetization curves of the Fe3O4 and
the final as-synthesized catalyst are shown in Figure 9.
Loading different layers on the Fe3O4 reduces the satura-
tion magnetization (from 54 emu/g in Fe3O4 to 25 emu/g
in the as-synthesized catalyst). However, the magnetiza-
tion (25 emu/g) is enough that Fe3O4@CQD@Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu
FIGURE 10 Size distribution of the as-synthesized catalyst,
namely Fe3O4@CQD@Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu catalyst
nanoparticles could be easily recovered from reaction
media using an external magnet.
TABLE 1 Effect of various solvents on the reaction time and
3.1.7 | Size distribution
yield (in the presence of the as-synthesized catalyst)
Figure 10 shows the size distribution of the as-
synthesized particles. The mean size value of the particles
with a 95% probability of random errors is equal to 21.55
5.38 nm. This result implies that the as-synthesized
particles have a nanoscale diameter.
Yield[a] (%)
Entry
Solvent
---
Time (min)
60ꢀC
90
1
2
3
4
5
6
5
13
17
15
20
13
EtOAc
CH3CN
H2O
75
69
84
3.1.8 | Heterogeneity test
n-Hexane
EtOH
37
88
For the proof of heterogeneity, two reactions were carried
out in parallel in two test tubes using β-naphthol,
aIsolated yield.
TABLE 2 Levels of the
runs
X1 (amount of catalyst)
X2 (temperature)
Yield (%)
independent variables and the
1
0.05
0.03
0.03
0.01
0.05
0.03
0.01
0.03
0.01
0.05
0.03
70
110
70
82
74
75
60
61
73
49
58
70
84
69
corresponding reaction yields using the
CCD method
2
3
4
70
5
30
6
70
7
30
8
30
9
110
110
70
10
11
Abbreviation: CCD, central composite design.

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AKBARPOUR ET AL.
benzaldehyde, and morpholine as starting materials at
110ꢀC and solvent-free condition (0.05 gr catalyst). After
2.5 min, one of them was stopped completely with a yield
equal to 42%. At the same time, the catalyst was sepa-
rated from the reaction medium in another test tube and
the reaction was continued without catalyst for up to
30 min with a yield equal to 44%. No significant change
in % conversion confirms the heterogeneity and role of
the as-synthesized catalyst.
investigate the effect of solvent on the reaction yield
and time. The prototype reaction was carried out in
ethyl acetate, CH3CN, H2O, n-hexane, EtOH, and
solvent-free condition. The results are given in Table 1.
As is provided, solvents increase the reaction time to
achieve a specified reaction yield. That is, the solvent-free
condition has the minimum and maximum reaction time
and yield, respectively. So the solvent-free condition was
used to investigate the reaction further. The isolated
yield, in this table, indicates the recrystallization yield in
ethanol.
4 | EVALUATION OF THE
CATALYTIC ACTIVITY OF NANO-
Fe3O4@CQD@ Si (OEt)(CH2)3
NH@CC@N3@phenylacetylene
@Cu catalyst
4.2 | Effect of catalysts and temperature
on the reaction yield by the design of
experiment
4.1 | Effect of solvent on the reaction
Briefly, central composite design (CCD) was used as a
design of experiment (DOE) method.[51–53] CCD is a
useful and practical subclass of response surface method-
ology (RSM) used to find a mathematical relationship
between the dependent variable (here reaction yield) and
independent variables (here temperature and the amount
of catalyst). For the selected prototype reaction, tempera-
ture (X1) and the amount of catalyst (X2) are two inde-
pendent variables that must change to find the maximum
yield of the reaction. Due to the importance of the central
experiment, it was carried out three times. The values of
the independent variables along with the corresponding
reaction yields are given in Table 2. It is important to
note that all reactions in Table 2 were stopped after 5 min
to investigate the effect of the catalyst and the
temperature.
The reaction between β-naphthol, benzaldehyde, and
morpholine was selected as a prototype reaction to
TABLE 3 Analysis of variance for reaction yield
Parameter
Model (yield)
X1
p-val. prob. > F
0.003
0.002
0.0005
0.86
X2
R2
Predicted R2
0.74
Lack of fit
0.32
FIGURE 11 Two- and three-dimensional reaction yields in terms of the amount of the catalyst and temperature

AKBARPOUR ET AL.
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TABLE 4 Synthesized 1-aminoalkyl-2-naphthols derivatives at the optimum prototype reaction condition using nano-Fe3O4@CQD@ Si
(OEt)(CH2)3NH@CC@N3@phenylacetylene@Cu catalyst
Product
1
2
3
4
5
m.p. (ꢀC)
Yield
181–184
131–134
116–120
190–192
174–178
93
5
89
3
85
7
73
9
81
5
Time (min)
Product
6
7
8
9
10
m.p. (ꢀC)
Yield
176–179
126–128
181–183
183–188
198.4–202
94
9
95
5
86
8
91
6
83
5
Time (min)
Product
11
12
13
14
15
m.p. (ꢀC)
Yield
160–164
160–167
160–161
196.8–197.2
197.4–198
81
12
16
78
6
75
8
69
5
75
6
Time (min)
Product
17
18
19
20
m.p. (ꢀC)
Yield
188.2–191.2
156.7–164
159.5–161
193.1–194.3
180–183.5
58
5
70
8
84
7
72
10
73
10
Time (min)
(Continues)

12 of 18
AKBARPOUR ET AL.
TABLE 4 (Continued)
Product
21
22
23
24
25
m.p. (ꢀC)
Yield
159.5–164
159–161
165–171
71
205–211
63
198–202
77
58
12
88
8
Time (min)
Product
10
14
12
26
27
28
29
30
m.p. (ꢀC)
Yield
188–196
197–204
188–189
167–168.5
153–158
72
6
84
5
72
8
69
9
76
5
Time (min)
Product
31
32
33
34
35
m.p. (ꢀC)
Yield
180–182.6
150–152
181–184
131–134
116–120
82
6
73
9
93
5
89
3
85
7
Time (min)
Statistical methods are used to find a mathematical
relation between independent and dependent variables.
Statistical analysis showed that a linear model could
best describe this relation. The linear model shows that
there is no interaction between temperature and cata-
lyst. The analysis of variance (ANOVA), also, is given
in Table 3. The value of the correlation coefficient (R2)
for the reaction yield is equal to 0.86 indicates a good
agreement between the experimental results and the
obtained linear model. The value of p-value (0.003),
also, indicates that the model is statistically significant
and reliable (Table 3).
The following expression states the dependency of
reaction yield to the temperature and the amount of
catalyst.
Yield ¼ 39:14þ400ꢂX1 þ0:25ꢂX2
In general, expressions marked with + and - have an
increasing and decreasing effect on the reaction yield,

AKBARPOUR ET AL.
13 of 18
respectively. The magnitude of the effect of X on reaction
yield is indicated by the coefficient values. Figure 11
shows the two- and three-dimensional reaction yields in
terms of the amount of the catalyst and temperature. This
figure shows that as the amount of catalyst and tempera-
ture increases, the amount of reaction yield increases so
that the 0.05-gr catalyst and 110ꢀC are the optimum
reaction condition.
4.3 | Synthesis of the 1-aminoalkyl-
2-naphthols derivatives at optimum
condition
SCHEME 3 The plausible proposed mechanism for the
synthesis of 1-aminoalkyl-2-naphthols derivatives using the as-
synthesized catalyst, namely, Fe3O4@CQD@ Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu
Using the obtained optimal reaction condition for the
prototype reaction, different derivatives of 1-aminoalkyl-
2-naphthols were synthesized using β-naphthol, various
aryl halides, and secondary amines (morpholine and
piperidine) in the presence of the as-synthesized
catalyst. These derivatives are given in Table 4 with their
values of time, crystallization reaction yield after
completion of corresponding reaction, and melting point.
As Table 4 shows, these derivatives can be obtained with
moderate to high yield (67%–95%) and short reaction
times (3–15 min). The characterizations of the synthe-
sized products are given in the supporting information
DATA S1.
Table 5 provides the some recent research in the
synthesis of 1-aminoalkyl-2-naphthols derivatives using
glycerol,[15] acidic alumina in MW,[18] ionic liquid,[20]
Fe3O4 MNPs,[17] catalyst-free,[54] Triton X-100,[16] and
DES (urea: choline chloride)[14] as catalysts. As given in
Table 4 the as-synthesized copper-based heterogeneous
magnetic nanocatalyst gives the maximum yield at low
time, namely, 5 min than mentioned studied catalysts. In
addition, the reaction between β-naphthol, benzaldehyde,
FIGURE 12 The yield of the prototype reaction versus cycles
using Fe3O4@CQD@ Si (OEt)(CH2)3NH@CC@N3
@phenylacetylene@Cu as-synthesized catalyst
TABLE 5 Comparison of the as-synthesized copper-based nanocatalyst with the available research catalyst, including catalyst type,
condition, time, and yield
Entry
Catalyst
Condition
Time
1–3 h
10 min
2.5 h
25 min
5 min
1 h
Yield
95
Reference
[14]
1
2
3
4
5
6
7
8
DES (urea:choline chloride)
Glycerol
DES 1 ml, 60ꢀC
[15]
[16]
[17]
[18]
[20]
[54]
2 ml cat, 90ꢀC
71
Triton X-100
5 mol % cat H2O, r.t.
0.1 g cat, U. S, 80ꢀC
2 g cat, solvent-free 80ꢀC
1 eq cat, EtOH, 80ꢀC
Dichloromethane, r.t.
0.05 g cat, S. F, 104ꢀC
93
Fe3O4 magnetic nanoparticles
Acidic alumina in MW
Ionic liquid
90
73
85
Catalyst-free
2 h
90
This work (nanocatalyst)
5 min
93
-
Abbreviations: r.t., room temperature, MW, microwave.

14 of 18
AKBARPOUR ET AL.
FIGURE 13 Energy-dispersive X-ray
spectroscopy (EDX) of the recovered
Fe3O4@CQD@ Si (OEt)
(CH2)3NH@CC@N3@phenylacetylene@Cu
catalyst
FIGURE 14 Mapping of the recovered Fe3O4@CQD@ Si (OEt)(CH2)3NH@CC@N3@phenylacetylene@Cu catalyst

AKBARPOUR ET AL.
15 of 18
and morpholine as starting materials was carried out
using Cu (OAc)2.2H2O, dry Cu (OAc)2, and the as-
synthesized catalyst. Both Cu (OAc)2.2H2O, dry Cu
(OAc) provide yield equal to 62%, while the as-
synthesized catalyst provides yield equal to 93%. All three
reactions were stopped after 5 min. These findings con-
firm the effective catalytic activity of the as-synthesized
catalyst compared to the Cu (OAc)2.2H2O, dry Cu
(OAc)2.
catalyst attacks the imine intermediate. Aromatization
driving force entails the formation of 1-aminoalkyl-
2-naphthols.
6 | RETRIEVAL OF THE
CATALYST
After completion of the prototype reaction at the
obtained optimum condition, the as-synthesized catalyst
was separated using an external magnet and used in the
next cycles. The reduction in reaction yield compared to
the different cycles is shown in Figure 12, so that the cat-
alyst provides 87.5% reaction yield after five cycles. Reac-
tions were stopped at 5 min per cycle. IR, EDX, and
mapping analyses were taken to examine the stability of
the recovered catalyst. Figure 13 presents the EDX of the
as-synthesized retrieved catalyst, so that all elements,
especially Cu with 2.4 wt%, are present in the recovered
catalyst. Elemental mapping was used to further investi-
gate the stability of the retrieved catalysts so that the
qualitative spatial distribution of constituent elements
including Fe, O, C, Si, N, and Cu is given in Figure 14. As
is shown in this figure, all elements, in particular
Cu, are present in the retrieved catalyst. This
finding provides strong evidence for the stability of the
as-synthesized novel copper-based heterogeneous mag-
netic nanocatalyst.
5 | PROPOSED MECHANISM
The proposed mechanism for the prototype reaction
is given in Scheme 3. To investigate the
reaction mechanism, IR spectra were taken from the
mixture of Fe3O4@CQD@Si (OEt)(CH2)3NH@CC@N3
@phenylacetylene@Cu with benzaldehyde or β-naphthol
or morpholine. The IR spectrum shows that the catalyst
does not react with morpholine because there is no
change in the wave number, but the catalyst interacts
with benzaldehyde and beta naphthol so that the wave
number in benzaldehyde shifts from 1686 to 1662 cmꢁ1
and the wave number of the hydroxy group in beta naph-
thol shifts from 3209 to 3218 cmꢁ1. These evidences
imply that the copper present on the catalyst surface
interacts with the carbonyl group of the benzaldehyde
and the hydroxy groups of the β-naphthol that triggers
the reaction. Based on these evidences, the proposed
mechanism is given in Scheme 3. As is seen in Scheme 3,
in the first stage, the as-synthesized catalyst interacts
with benzaldehyde and then morpholine attacks the
benzaldehyde, creating an imine intermediate. In the
next step, the activated β-naphthol by the as-synthesized
In another study, the TEM technique was used to
confirm and re-prove the structure of the recovered cata-
lyst. First, the catalyst was used in the six cycles so that
Figure 15 displays the TEM images of the recovered
catalyst. Compared to the intact catalyst (Figure 5), the
structure of the recovered catalyst did not change
FIGURE 15 Transmission electron microscopy (TEM) micrographs of the as-synthesized heterogeneous recovered catalyst after six
cycles

16 of 18
AKBARPOUR ET AL.
FIGURE 16 Thermal gravimetric analysis
(TGA) and differential thermal analysis (DTA)
analysis of the as-synthesized catalyst after six
cycles of recovery
FIGURE 17 The FTIR spectra of the as-
synthesized catalyst before and after six cycles of
recovery
significantly. It should be noted that these two catalysts
(intact and recovered) have been synthesized in different
batches and differences can be due to this issue.
proves the stability of the as-synthesized catalyst even
after the recovery.
Also, the TGA analysis of the recovered catalyst after
six cycles was used to demonstrate the possible changes
before and after the performance tests (Figure 16). As is
shown, the recovered catalyst has multiple step-changes
in mass similar to the neat as-synthesized catalyst. These
analytical findings confirm the stability of the provided
catalyst.
To further investigate the as-synthesized catalyst's sta-
bility, the FTIR spectrum was taken from the recovered
catalyst after six cycles. Figure 17 compares the FTIR of
the as-synthesized catalyst before and after recovery. As
is shown, the FTIR of the recovered catalyst does not
change compared to the virgin catalyst considerably. This
7. CONCLUSION
The proposed precise and engineered method, in sum-
mary, can be used to synthesize novel Lewis acid-based
heterogeneous catalysts, including Cu, Co, etc. These
types of catalysts can be used in various organic transfor-
mations that require a Lewis acid. Of the solvent-free
condition, low reaction time, high reaction yield, mild
reaction condition, and stability of catalyst all are the
main features of the as-synthesized catalyst. Besides, the
findings of this study show that the use of DOE in
organic chemistry to find the optimal conditions is a

AKBARPOUR ET AL.
17 of 18
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ACKNOWLEDGMENTS
The authors gratefully acknowledge partial support of
this work by the Research Affairs Office of Bu-Ali Sina
University (Grant number 32-1716 entitled development
of chemical methods, reagents and molecules), Center of
Excellence in Development of Chemical Method
(CEDCM), Hamedan, I. R. Iran.
AUTHOR CONTRIBUTIONS
Tahereh Akbarpour: Conceptualization; data curation;
formal analysis; methodology. Ardeshir Khazaei:
Funding acquisition; resources; supervision. Jaber
Yousefi Seyf: Project administration; software;
supervision; validation; visualization. Negin Sarmasti:
Investigation; methodology; project administration.
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J. Iran. Chem. Soc. 2020, 17, 1775.
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I. Ali Arabian, Appl. Organomet. Chem. 2020, 34, e5449.
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M. Mahmoudiani Gilan, Polycycl. Aromat. Compd. 2021,
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DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are avail-
able in the supplementary material of this article.
ORCID
Tahereh Akbarpour https://orcid.org/0000-0002-0609-
1228
Ardeshir Khazaei https://orcid.org/0000-0001-7990-
2266
Jaber Yousefi Seyf https://orcid.org/0000-0001-5919-
0206
Negin Sarmasti https://orcid.org/0000-0002-0319-0909
[32] A. Khazaei, N. Sarmasti, J. Yousefi Seyf, J. Mol. Liq. 2018,
262, 484.
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
How to cite this article: T. Akbarpour,
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