Magnetic acyclovir-copper nanoparticle: DFT study and application as an efficient, magnetically separable and recyclable catalyst for N-arylation of amines under green condition

Article abstract of DOI:10.1016/j.inoche.2020.108240

A copper(I)‐acyclovir complex supported on magnetic was designed and successfully synthesized. Catalytic activity and stability of two structures of copper(I)‐acyclovir complex supported on magnetic were investigated by the theoretical method. The more active and stable copper(I)‐acyclovir complex supported on magnetic was applied as a catalyst for C–N cross‐coupling reaction with high yield in a deep eutectic solvent (DES) as a green solvent. Also, these nanoparticles could be easily recovered and reused for new rounds of reaction without any considerable loss in catalytic activity.

Full text of DOI:10.1016/j.inoche.2020.108240

InorganicChemistryCommunications122(2020)108240
Contents lists available at ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Short communication
Magnetic acyclovir-copper nanoparticle: DFT study and application as an
efficient, magnetically separable and recyclable catalyst for N-arylation of
amines under green condition
Farzane Pazoki, Akbar Heydari⁎
Department of Chemical, Faculty of Sciences, Tarbiat Modares University, Tehran 14117-13116, Iran
G R A P H I C A L A B S T R A C T
A R T I C L E I N F O
A B S T R A C T
This article is dedicated to the memory of
Mostafa Chamran.
A copper(I)‐acyclovir complex supported on magnetic was designed and successfully synthesized. Catalytic
activity and stability of two structures of copper(I)‐acyclovir complex supported on magnetic were investigated
by the theoretical method. The more active and stable copper(I)‐acyclovir complex supported on magnetic was
applied as a catalyst for C–N cross‐coupling reaction with high yield in a deep eutectic solvent (DES) as a green
solvent. Also, these nanoparticles could be easily recovered and reused for new rounds of reaction without any
considerable loss in catalytic activity.
Keywords:
Nanocatalyst
Cross‐coupling
Theoretical method
Acyclovir
1. Introduction
reported different metal-chelating ligands as a catalyst for the N-ar-
ylation of nitrogen containing hetero cycles.[1,6–9] Traditionally, the
Developing an efficient route for the preparation of nitrogen-con-
taining compounds is an important area of study in the preparation of
organic compounds because aryl subunits are generally found in bio-
logical [1,2], pharmaceutical [3,4], and materials sciences[5].
In a series of papers started in 1999, Buchwald and co-workers were
coupling of aryl halides with amines has been performed under Ull-
mann-type conditions at high temperature with the stoichiometric
amount of copper and the yields are not very reproducible [10].
Various catalytic systems have been employed for the arylation of
nitrogen heterocycles include the use of Cu2O [9], Cu@SB@MCM-41
⁎ Corresponding author at: Chemistry Department, Tarbiat Modares University, PO Box 14155-4838, Tehran, Iran.
E-mail address: heydar_a@modares.ac.ir (A. Heydari).
https://doi.org/10.1016/j.inoche.2020.108240
Received 25 July 2020; Received in revised form 24 August 2020; Accepted 10 September 2020
Availableonline16September2020
1387-7003/©2020ElsevierB.V.Allrightsreserved.

F. Pazoki and A. Heydari
InorganicChemistryCommunications122(2020)108240
[11], CuI [12], CuBr [13], Cu(II)ttpy [14], Fe3O4@SiO2‐TCT‐NH2 [15],
Cu-HB@AS-MNPs [16] and CuFe2O4 [17].
orthosilicate (TEOS) in basic aqueous medium with pH about 11. This
solution was refluxed for 24 h, the final product thoroughly washed
with deionized water and ethanol until the solution was neutral and
dried in an oven at 50 °C. After that, 1.0 g of Fe3O4@SiO2 was dispersed
in toluene. 10 mmol (3-chloropropyl)triethoxysilane was added to this
solution. This solution was refluxed for 24 h. Afterward, the final pro-
duct separated by a magnet, next washed with distilled water and
ethanol three times until neutralization and dried in an oven for 24 h.
The Fe3O4@SiO2-Si(CH2)3N-acyclovir was prepared by dispersing
Fe3O4@SiO2-Si(CH2)3Cl in toluene and 2.0 mmol acyclovir was added
to this solution. This solution was refluxed for 24 h. Then, the final
product separated by a magnet, next washed with distilled water and
ethanol three times until neutralization and dried in an oven for 24 h.
The product was dispersed in THF and 0.5 mmol CuI was added to
solution and stirred for 24 h. Finally, the final product separated by a
magnet, next washed with distilled water and ethanol three times until
neutralization, and dried in an oven for 24 h [22] (Scheme 1)
Despite the advantages of these methods, there have problems in-
cluding the use of recyclability and reusability of catalysts for several
runs, harsh reaction conditions and high-cost reagents. Therefore, there
is a need for the improving methods that performed by using nontoxic,
suitable and inexpensive reagent, possible as well as environmentally
route for the arylation of nitrogen heterocycles.
Herein, we describe the development of magnetic nanoparticles that
show many attributes of the perfect catalyst for example, an effective
surface, low cost, thermal stability and recoverability. Copper
(I)‐acyclovir complex immobilized on the surface of magnetic nano-
particles, Fe3O4@ acyclovir–Cu(I) is a robust and safe nanocatalyst for
the arylation of nitrogen heterocycles in ethylene glycol with K2CO3 as
deep eutectic solvents.
Solvents also play a considerable role in green reactions. The major
problems of using solvents are their volatile nature, adverse impacts on
environment [18]. Deep eutectic solvents as an important category of
promising solvents have desirable properties such as cheap, sustainable,
low toxicity, biodegradability and compatibility for applying to in-
dustrial processes [19]. Deep eutectic solvents are prepared by two or
three components which can be to establish the varieties ratios of
ammonium or phosphonium based salts with different hydrogen bonds
[20]. In this study, we decided to use potassium carbonate and ethylene
glycol (EG) as a DES.
2.3. General procedure for C–N cross‐coupling
A mixture of amine (1.0 mmol), aryl halide (1.0 mmol) and Fe3O4@
SiO2-Si(CH2)3N-acyclovir-Cu(I) (0.020 g) in DES (4 mL) was stirred at
100 °C for 2 h. Upon completion, the Fe3O4@SiO2-Si(CH2)3N-acyclovir-
Cu(I) was separated by an external magnet. Finally, the product was
decanted by dilution of the residue with water and separated the
magnetic catalyst by a magnet and the residue was isolated by column
chromatography on silica gel (70–230 Mesh) using n-hexane–ethyl
acetate (4:1) to afford the desired product. The melting point, FT-IR,
mass and 1HNMR analyses of products are in supporting information.
Hence, in continuation of our efforts in the development of simple
and efficient protocols for arylation of nitrogen heterocycles [21]. We
attempted to report the synthesis of Fe3O4@SiO2-Si (CH2)3N-acyclovir-
Cu(I) as a robust, renewable, efficient and environmentally friendly
catalyst for arylation of nitrogen heterocycles with high yields in DES.
Also in this research, two different structures of Copper(I)‐acyclovir
complex supported on magnetic were investigated in the catalytic ac-
tivity of nanoparticles and physicochemical properties by the theore-
tical method.
3. Computational
3.1. Computational details
The quantum chemical calculations were performed by GAMESS
software DFT method, B3LYP functional and 6-31G (d) basis set was
used on each step to predict the optimization molecular structure. Two
structure of copper(I)‐acyclovir complex supported on magnetic were
designed and the geometry optimization of Fe3O4@SiO2-Si(CH2)3N-
acyclovir-Cu(I), Fe3O4@SiO2-O-acyclovir-Cu(I) and acyclovir shown in
Fig. 1. DFT calculations, including natural bonding orbitals (NBO),
highest occupied molecular orbital (HOMO), and lowest unoccupied
molecular orbital (LUMO) were carried out aiming at providing effec-
tive information for understanding the physicochemical properties and
proposed interactions between Copper (I)‐acyclovir complex supported
on magnetic and acyclovir.
2. Experimental
2.1. General
All required chemical were purchased from Aldrich chemical com-
panies. Structure of sample Fe3O4@SiO2-Si(CH2)3-N-acyclovir-Cu(I)
was recorded at 25 °C by X-ray diffraction (a Philips X‐Pert 1710 dif-
fractometer at a voltage of 40 kV and current of 40 mA in the 2θ range
of 5– 80°) and fourier transform infrared (FT-IR) spectra were collected
with spectroscopic grade KBr (Nicolet IR100). The morphology of the
powder catalyst was studied using a Philips XL 30 and S‐4160 scanning
electron microscope with energy‐dispersive X‐ray (EDX) spectroscopy
capability. Inductively coupled plasma (ICP) analyses was performed
using a Varlan Vista-Pro ICP-OE spectrometer. The magnetic properties
were measured with a vibrating sample magnetometer (VSM) (LDJ
9600-1, USA).
3.2. Computational assessment
3.2.1. Density functional theory calculations
The DFT calculations [23] were computed by GAMESS software
[24] at the DFT/b3lyp/ 6-31G in order to compare stability of the
different copper(I)‐acyclovir complex supported on magnetic systems
that could be obtained. B3LYP functional and 6-31G basis set were used
to predict the optimization molecular structure. This is shown in Fig. 1,
structure 1 is determined when the nitrogen of acyclovir reacts with the
MNPs, while structure 2 is formed by reaction of oxygen of acyclovir
with the MNPs. Relevant energy Gibbs (ΔG) and enthalpy (ΔH) de-
pending on the optimized structures were calculated. These results in-
2.2. Preparation of the Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I)
Fe3O4 was synthesized by dissolving a mixture iron (II) and iron (III)
salts as sources in distilled water under vigorous stirring (800 rpm) with
dropwise addition of NH4OH to produce a black solid product then the
mixture was refluxed for 1 h under argon. Afterward, the solid product
separated by a magnet, next product was washed with distilled water
and ethanol three times until neutralization and dried in an oven for
24 h. The next step was performed to form Fe3O4@SiO2 using tetraethyl
dicate that structure
1
is
a
little more stable (nearly
−20.000 × 10−18 KJ mol−1) than structure 2 (−19.487 × 10−18).
2

F. Pazoki and A. Heydari
InorganicChemistryCommunications122(2020)108240
Scheme 1. Preparation of the Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I).
3.2.2. NBO
The peaks at around 1083 cm−1 are depended on Si–O stretching. Vi-
bration in the FT-IR spectra of Fe3O4@SiO2-Si(CH2)3N-acyclovir (Green
curve) at 1527 cm−1 with Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I)
(Black curve) at 1631 cm−1 prove the formation of the complex. Also,
the FT-IR of Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) nanoparticles be-
fore and after reaction are shown. The comparison of these leads to the
conclusion that there is not much difference in the structures between
the particles before and after reaction and this the structure is stable.
To give information about the elements present in Fe3O4@SiO2-Si
(CH2)3N-acyclovir-Cu(I) EDX analysis was used (Fig. 4). EDX pattern
indicates the good dispersion of magnetic nanoparticle and shown
elements composition of the typical sample shows including Fe, Si, N, C,
Cu and I. ICP mass spectrometry revealed that the loading of copper of
According to the NBO analysis, atomic charge of acyclovir was in-
vestigated and shows in Fig. 2 and Table 2 SD (supporting information).
We obtained from NBO calculations the atomic charge of N 10 is more
than atomic charge of O26. The atomic charge of N10 and O26 is
−0.843 and −0.755 respectively.
3.2.3. Analysis of orbital energies
The molecular orbital energy diagrams for the highest occupied
molecular orbitals (HOMOs), the lowest unoccupied molecular orbitals
(LUMOs) and band gap for Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) and
Fe3O4@SiO2-O-acyclovir-Cu(I) were calculated. It is well-known that
the frontier orbitals effect on the chemical stability of a molecule [25].
The energy difference between the HOMO and LUMO (HOMO–LUMO
gap) indicates the chemical activity of the material due to the HOMO
represents electron-donating ability, and the LUMO characterizes
electron accepting ability. The Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I)
and Fe3O4@SiO2-O-acyclovir-Cu(I) differs on the possibility of ad-
justing the width of the band gap. The band gap obtained 0.17 × 10−18
and 0.2 × 10−18 J for compound Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu
(I) and Fe3O4@SiO2-O-acyclovir-Cu(I) respectively. Therefore, the
Fe3O4@SiO2-SiO2(CH2)3N-acyclovir-Cu(I) is more effective than
Fe3O4@SiO2@O-acyclovir-Cu(I) and has high catalytic activity.
the Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) NPs was 0.25 mmol g−1
.
Thermogravimetric analysis of the nanoparticles was used for in-
vestigation of the percent of organic functional groups chemisorbed
onto the surface of Fe3O4@SiO2-SiO2(CH2)3N-acyclovir-Cu(I) (Fig. 5).
The TGA pattern of the Fe3O4@SiO2-SiO2(CH2)3N-acyclovir-Cu(I) was
obtained at a rate of 20 °C/min within the range of 20–800 °C in ni-
trogen atmosphere. The first weight loss observed nearby 210 °C is
probably depended on evaporation of physisorbed water. The second
peak at rang 210 °C and 530 °C which is a feature of the surface
functionalities and the decomposition of the acyclovir complex. Also,
correspondent thermal analysis, this catalyst was stable up to 210 °C.
Fig. 6 exhibits the XRD spectra of Fe3O4 @SiO2 (red curve) Fe3O4@
SiO2-SiO2(CH2)3N-acyclovir-Cu(I) (blue curve). The XRD pattern of
nanoparticle shows diffraction peaks about (34°, 42°, 50°, 62°, 67° and
74°) corresponding to a typical spinel Fe3O4 structure and these peaks
match [21,29–31], these reveal that the structure of Fe3O4 remains
after surface modification. Also, the diffraction peak of the amorphous
silica shell was obvious at 25° [32,33].
4. Results and discussions
The FT-IR spectra of the Fe3O4@SiO2 (Blue curve), Fe3O4@SiO2-Si
(CH2)3N-acyclovir (Green curve), and Fe3O4@SiO2-Si(CH2)3N-acy-
clovir-Cu(I) before (Black curve) and after reaction (Yellow curve) were
shown in Fig. 3. The peaks that appeared at around 555 cm−1 and
462 cm−1 are related to the bond Fe-O stretching vibration [26–28]. On
the spectrum region around 3415 cm−1 due to O-H vibrations of water.
Morphological studies of Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I)
3

F. Pazoki and A. Heydari
InorganicChemistryCommunications122(2020)108240
(Blue curve), and Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) (Black curve)
were characterized by VSM at room temperature (Fig. 8). The satura-
tion magnetization of Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) is around
22.1 emu/g which accounts for easy recovery of this catalyst and the
magnetization curve demonstrate that these Fe3O4@SiO2-Si(CH2)3N-
acyclovir-Cu(I) nanoparticles have superparamagnetic properties. The
formation of Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) performed be-
cause Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) nanoparticles have lower
magnetization in comparison with that of Fe3O4.
Nitrogen-containing heterocycles are broadly applied in the phar-
maceutical industry. This route was selected to evaluate the environ-
mental effect of coupling of aryl halides with amines. DES is a green
solvent which expanding a safe and inexpensive technique for pre-
paration of heterocycles compounds. Our preliminary experiments in-
dicate that Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) is a more effective
promoter for the safe and suitable catalyst for coupling of aryl halides
with amines. The yields of coupling of aryl halides with amines, and
catalyst of Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) was investigated by
different solvent, temperature and amount catalyst are listed in Table 1
(Entries 1–11).
Initially, the reaction performed leisurely in DMF, H2O, dioxane,
dichloromethane and DES (Table 1). The reaction is carried out in 24 h
in DMF, H2O, dioxane, dichloromethane that this time is higher than
the reaction when DES was used as a solvent (2 h). At the next step, to
evaluate the effect of amount catalyst, we used the 10, 15, 20 and
25 mg of the nanocatalyst to investigate the suitable amount of catalyst
(Table 1, Entry 8, 9, 10 and 6) that the best result for reaction was
20 mg. Finally, we studied the reaction temperature. The improvement
in the yield take placed by increasing the temperature to 80 °C.
Also, the reaction was studied in the presence of Fe3O4@SiO2-Si
(CH2)3N-acyclovir-Cu(I) without K2CO3 and in the presence of K2CO3
without Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I). Therefore, The co-
operation of Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) and K2CO3 is es-
sential for performing this reaction.
Fig. 1. Complete molecular graphs (MGs) of the (1) and the (2) obtained with
b3lyp/ 6-31g electron density functions.
was carried out using FE-SEM micrographs as shown in Fig. 7. Fe3O4@
SiO2-Si(CH2)3N-acyclovir-Cu(I) has an approximate diameter of
50–60 nm with nearly spherical shapes.
The magnetic properties of the Fe3O4 (Red curve), Fe3O4@SiO2
Different molar ratios of EG to K2CO3 were investigated by various
Fig. 2. Complete molecular graphs (MGs) of the acyclovir obtained with b3lyp/ 6-31g electron density functions.
4

F. Pazoki and A. Heydari
InorganicChemistryCommunications122(2020)108240
Fig. 3. The FT-IR spectra of the Fe3O4@SiO2 (Blue curve), Fe3O4@SiO2-Si(CH2)3N-acyclovir (Green curve), and Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) before (Black
curve) and after reaction (Yellow curve). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 4. EDX analysis of various elements on the surface of the Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) NPs.
Fig. 5. TGA of Fe3O4 (red curve), Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) (blue curve). (For interpretation of the references to colour in this figure legend, the reader
is referred to the web version of this article.)
5

F. Pazoki and A. Heydari
InorganicChemistryCommunications122(2020)108240
Fig. 6. The X-ray diffraction pattern of Fe3O4 @SiO2 (red curve) Fe3O4@SiO2-SiO2(CH2)3N-acyclovir-Cu(I) (blue curve). (For interpretation of the references to
colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 7. FE-SEM micrographs of a) Fe3O4 b) Fe3O4@SiO2-SiO2(CH2)3N-acyclovir-Cu(I).
The best result was obtained by using 20 mg Fe3O4@SiO2-Si
(CH2)3N-acyclovir-Cu(I) at 80 °C in DES (Entry 8).
The efficiency of the Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) was
compared with Fe3O4 under similar conditions (Table 2). When Fe3O4@
SiO2-Si(CH2)3N-acyclovir-Cu(I) resulted in yield better than Fe3O4
(Table 2, Entry 2 and 3). Also, no product was obtained when the re-
action was performed without any catalyst (Table 2 Entry 1).
The reaction conditions of coupling of aryl halides with amines were
performed by using the optimized conditions described above. Finally,
the products were acquired in good to excellent yields and can be seen
in Table 3.
When 4-chloroaniline and 4-nitroiodobenzene with benzyl bromide
and 3-nitroiodobenzene were used in the reaction, the corresponding
product was provided in the excellent yield (Table 3, Entry 3 and 3).
Iodobenzene and 2-amino pyridine was reacted to obtain the product in
the good yield (Table 3, Entry 11).
Fig. 8. VSM of the Fe3O4 (Red curve), Fe3O4@SiO2 (Blue curve), and Fe3O4@
4.1. Recycling of the catalyst
SiO2-Si(CH2)3N-acyclovir-Cu(I) (Black curve). (For interpretation of the refer-
ences to colour in this figure legend, the reader is referred to the web version of
this article.)
The reusability of the catalyst is the principal advantage for an ef-
ficient heterogeneous catalyst. It is revealed that the Fe3O4@SiO2-Si
(CH2)3N-acyclovir-Cu(I) nanoparticle catalyst can be recovered and
reused five times without any loss of the activity (Fig. 9 a). Also, the
XRD and SEM of Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) nanoparticles
after reaction are shown in Fig. 9 b and c. The comparison of these leads
EG molar ratio at a fixed amount of K2CO3. The best molar ratio was
molar ratio of 1:4 EG to K2CO3 for this reaction due to this molar ratio
has excellent yield.
6

F. Pazoki and A. Heydari
InorganicChemistryCommunications122(2020)108240
Table 1
Optimization of the reaction conditions of coupling of aryl halides with amines.
Entry
Amount of catalyst (mg)
Solvent
Base
Temperature (°C)
Yield (%)d
1
20
20
20
20
20
20
20
20
20
15
10
20
25
DMFa
Triethylamine
Triethylamine
Triethylamine
Triethylamine
K2CO3
100
100
100
60
75
–
2
H2Oa
3
Dioxanea
70
80
90
90
80
30
90
85
75
85
90
4
Dichloromethanea
5
EGb
EGb
EGb
EGb
EGb
EGb
EGb
EGc
EGb
100
80
6
K2CO3
7
K2CO3
60
7
K2CO3
25
8
K2CO3
80
9
K2CO3
80
10
11
12
K2CO3
80
K2CO3
80
K2CO3
80
Reaction conditions:
a
b
c
Aniline (1.2 mmol), bromo benzene (1.0 mmol) and triethylamine (2.0 mmol) in various solvent (3.0 mml) in presence of Fe3O4@creatine-Cu(I) (0.02 g) for 24 h.
Aniline (1.2 mmol), bromo benzene (1.0 mmol) in DES (with molar ratio 1:4) at presence of Fe3O4@SiO2-Si(CH2)3N-Acyclovir-Cu(I) (20 mg) for 2 h.
Aniline (1.2 mmol), bromo benzene (1.0 mmol) in DES (with molar ratio 1:5) at presence of Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) (20 mg) for 2 h.
Isolated yield.
d
Table 2
Table 3
Screening of the catalysts.
Products of coupling of aryl halides with amines by
Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I).
Entry
Catalyst
Yield (%)
1
2
3
None
< 5%
90%
Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I)
Fe3O4@SiO2-O-acyclovir-Cu(I)
85%
to the conclusion that there is not much difference in the structure and
morphology between the particles before and after reaction and this the
structure is stable.
To explore the stability of the nanocatalyst, the leaching test was
performed. A mixture of nanoparticles (20 mg) in DES was stirred at
80 °C for 2 h. The Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) nanoparticles
were removed by dilution of the mixture with water and using an ex-
ternal magnet and the solution was analyzed by inductively coupled
plasma (ICP). This revealed that a little amount of Cu (< 1.5 ppm)
leached.
In comparison with other reported other catalytic systems for the N-
arylation of amines, Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) showed
good catalytic performance in terms of ecofriendly, facile separation,
activity and reusability in green solvent with short time (Table 4).
5. Conclusion
In conclusion, Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) was success-
fully prepared and catalytic activity and physicochemical properties of
two structure of Copper (I)‐ acyclovir complex supported on magnetic
nanoparticles were evaluated by the theoretical method. We find that
Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) were a stable formulation ra-
ther than Fe3O4@SiO2-O-acyclovir-Cu(I). Also, the development of
general methods for coupling of aryl halides with amines catalyzed
with Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) in DES as a green solvent
are highly desired in the case of from synthetic, environmental view-
points.
aCondition reaction: amine (1.0 mmol), aryl halide
(1.0 mmol) DES (with molar ratio 1:4) as a solvent at
presence
of
Fe3O4@SiO2-Si(CH2)3N-Acyclovir-Cu(I)
(20 mg) at 80 °C for 2 h.
7

F. Pazoki and A. Heydari
InorganicChemistryCommunications122(2020)108240
Fig. 9. The reusability of the a) Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) b) SEM of recycled Fe3O4@SiO2-SiO2(CH2)3N-acyclovir-Cu(I) catalyst after 5th use, c) XRD of
recycled Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) catalyst after 5th use.
Table 4
Comparison of the catalytic efficiency of Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu(I) with the previously reported catalytic systems in the N-arylation of amines reaction.
Entries
Catalyst
Reaction conditions
Yield (%)
1
FeCl3
amine (1.0 mmol), aryl halide (1.5 mmol), K3PO4,toluene at 135 °C for 24 h
Trace [34]
79 [35]
97 [36]
30 [37]
80 [21]
90
2
CuI
aryl halide (2 mmol), amine (3 mmol), ligand (0.4 mmol), K2CO3 (4 mmol) in DMF (3 mL) under N2 ;
aryl halide(4.0 mmol), amine (1.0 mmol), DAB (1) (6 mol%), KOtBu (3 mmol), toluene (5 mL) for 48 h at 120 °C
aryl halide(4.0 mmol), amine (1.0 mmol), KOH (2 mmol), and in DMSO (2 mL) at 100 °C for 1.30 h
aniline (1.2 mmol), bromobenzene (1.0 mmol) in DES at 80 °C for 24 h.
3
CuI
4
Fe3O4@TiO2/Cu2O
Fe3O4@creatine-Cu(I)
Fe3O4@SiO2-Si(CH2)3N-acyclovir-Cu
(I)
5
6a
Aniline (1.2 mmol), bromo benzene (1.0 mmol) in DES (with molar ratio 1:4) at presence of Fe3O4@SiO2-Si
(CH2)3N-Acyclovir-Cu(I) (20 mg) for 2 h
Declaration of Competing Interest
Appendix A. Supplementary material
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.inoche.2020.108240.
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
References
Acknowledgements
[1] B.T. Ingoglia, C.C. Wagen, S.L. Buchwald, Biaryl monophosphine ligands in palla-
dium-catalyzed C-N coupling: an updated User’s guide, Tetrahedron 75 (2019)
4199–4211.
Our research groups gratefully acknowledge Tarbiat Modares
University, Iran for partial financial support of this work.
[2] J.S.K. Clark, M.J. Ferguson, R. McDonald, M. Stradiotto, PAd2-dalphos enables the
8

F. Pazoki and A. Heydari
InorganicChemistryCommunications122(2020)108240
nickel-catalyzed C− N cross-coupling of primary heteroarylamines and (Hetero)
aryl chlorides, Angew. Chemie Int. Ed. 58 (2019) 6391–6395.
their use (2007).
[21] S. Bagheri, F. Pazoki, I. Radfar, A. Heydari, Copper (I)–creatine complex on mag-
netic nanoparticles as a green catalyst for N-and O-arylation in deep eutectic sol-
vent, Appl. Organomet. Chem. 34 (2020) e5447.
[3] Z. Jin, Muscarine, imidazole, oxazole and thiazole alkaloids, Nat. Prod. Rep. 22
(2005) 196–229.
[4] J.M. Dennis, N.A. White, R.Y. Liu, S.L. Buchwald, Pd-Catalyzed C-N coupling re-
actions facilitated by organic bases: mechanistic investigation leads to enhanced
reactivity in the arylation of weakly binding amines, ACS Catal. 9 (2019)
3822–3830.
[22] M.A. Zolfigol, R. Ayazi-Nasrabadi, S. Baghery, V. Khakyzadeh, S. Azizian,
Applications of a novel nano magnetic catalyst in the synthesis of 1, 8-dioxo-octa-
hydroxanthene and dihydropyrano [2, 3-c] pyrazole derivatives, J. Mol. Catal. A:
Chem. 418 (2016) 54–67.
[5] E. Azzali, M. Girardini, G. Annunziato, M. Pavone, F. Vacondio, G. Mori,
M.R. Pasca, G. Costantino, M. Pieroni, 2-Aminooxazole as a novel privileged scaf-
fold in antitubercular medicinal chemistry, ACS Med. Chem. Lett. (2020).
[6] B.Y. Park, M.T. Pirnot, S.L. Buchwald, Visible light-mediated (hetero) aryl amina-
tion using Ni (II) salts and photoredox catalysis in flow: a synthesis of Tetracaine, J.
Org. Chem. 85 (2020) 3234–3244.
[23] E.D. Glendening, A.E. Reed, J.E. Carpenter, F. Weinhold, Nbo Version 3.1, Tci,
Univ. Wisconsin, Madison 65 (1998).
[24] M.W. Schmidt, K.K. Baldridge, J.A. Boatz, S.T. Elbert, M.S. Gordon, J.H. Jensen,
S. Koseki, N. Matsunaga, K.A. Nguyen, S. Su, General atomic and molecular elec-
tronic structure system, J. Comput. Chem. 14 (1993) 1347–1363.
[25] M. Bonsaii, K. Gholivand, K. Abdi, A.A.E. Valmoozi, M. Khosravi, A combined ex-
perimental and computational study on the interaction of nitrogen mustards with
DNA, Medchemcomm. 7 (2016) 2003–2015.
[7] E.P.K. Olsen, P.L. Arrechea, S.L. Buchwald, Mechanistic insight leads to a ligand
which facilitates the palladium-catalyzed formation of 2-(Hetero) arylaminoox-
azoles and 4-(Hetero) arylaminothiazoles, Angew. Chemie Int. Ed. 56 (2017)
10569–10572.
[26] G. Pathak, K. Rajkumari, L. Rokhum, Wealth from waste: M. acuminata peel waste-
derived magnetic nanoparticles as a solid catalyst for the Henry reaction, Nanoscale
Adv. 1 (2019) 1013–1020.
[8] S.D. McCann, E.C. Reichert, P.L. Arrechea, S.L. Buchwald, Development of an aryl
amination catalyst with broad scope guided by consideration of catalyst stability, J.
Am. Chem. Soc. (2020).
[27] E. Karaoğlu, A. Baykal, M. Şenel, H. Sözeri, M.S. Toprak, Synthesis and character-
ization of piperidine-4-carboxylic acid functionalized Fe3O4 nanoparticles as a
magnetic catalyst for Knoevenagel reaction, Mater. Res. Bull. 47 (2012) 2480–2486.
[28] F. Pazoki, F. Mohammadpanah, A.S. Manesh, J.A. Mehraban, A. Heydari, Diphenyl
phosphate creatine immobilized on magnetite nanoparticles: an efficient and re-
cyclable catalyst for Aza-Michael reaction, J. Chem. Sci. 132 (2020) 30.
[29] Y. Jain, M. Kumari, R.P. Singh, D. Kumar, R. Gupta, Sonochemical decoration of
graphene oxide with magnetic Fe 3 O 4@ CuO nanocomposite for efficient click
synthesis of coumarin-sugar based bioconjugates and their cytotoxic activity, Catal.
Letters. 150 (2020) 1142–1154.
[9] R.A. Altman, E.D. Koval, S.L. Buchwald, Copper-catalyzed N-arylation of imidazoles
and benzimidazoles, J. Org. Chem. 72 (2007) 6190–6199.
[10] A.F. Pozharskii, B.K. Martsokha, A.M. Simonov, Direct N-arylation of five-mem-
bered nitrogen heterocycles, J. Gen. Chem. USSR 33 (1963) 994.
[11] M. Niakan, Z. Asadi, S. Zare, Preparation, characterization and application of
copper schiff base complex supported on MCM-41 as a recyclable catalyst for the
ullmann-type N-arylation reaction, ChemistrySelect. 5 (2020) 40–48.
[12] A. Shafir, P.A. Lichtor, S.L. Buchwald, N-versus O-arylation of aminoalcohols:
Orthogonal selectivity in copper-based catalysts, J. Am. Chem. Soc. 129 (2007)
3490–3491.
[30] F. Pazoki, J.A. Mehraban, M. Shamsayei, B. Bakhshi, R. Esfandiarpour, M.K. Miraki,
A. Heydari, Aza-michael addition of 5-substituted tetrazole catalysed by a novel
nanoparticle solid base catalyst involving a layered zinc hydroxide supported on a
ferrite core, ChemistrySelect. 4 (2019), https://doi.org/10.1002/slct.201804070.
[31] F. Pazoki, A. Salamatmanesh, S. Bagheri, A. Heydari, Synthesis and characterization
of copper (I)-cysteine complex supported on magnetic layered double hydroxide as
an efficient and recyclable catalyst system for click chemistry using choline azide as
reagent and reaction medium, Catal. Lett. (2019) 1–10.
[13] F. Wu, C. Nan, M. Ma, H. Li, J. Xie, Commercial drug norfloxacin as a novel ligand
for the copper-catalyzed N-arylation of imidazole with aryl halides, Appl.
Organomet. Chem. 33 (2019) e5195.
[14] H. Sharghi, A.A. Saei, M. Aberi, N-arylation of nitrogen-containing heterocycles
with Cu (II) complex of 4-(2, 2′: 6′, 2 “-terpyridin-4′-yl) toluene as a versatile and
efficient catalyst, ChemistrySelect. 4 (2019) 13228–13234.
[15] M. Esmaeilpour, A.R. Sardarian, H. Firouzabadi, Dendrimer-encapsulated Cu (Π)
nanoparticles immobilized on superparamagnetic Fe3O4@ SiO2 nanoparticles as a
novel recyclable catalyst for N-arylation of nitrogen heterocycles and green
synthesis of 5-substituted 1H-tetrazoles, Appl. Organomet. Chem. 32 (2018) e4300.
[16] R. Zahedi, Z. Asadi, F.D. Firuzabadi, A highly active, recyclable and cost-effective
magnetic nanoparticles supported copper catalyst for N-arylation reaction, Catal.
Lett. 150 (2020) 65–73.
[32] Y. Zheng, K. Ma, H. Li, J. Li, J. He, X. Sun, R. Li, J. Ma, One pot synthesis of imines
from aromatic nitro compounds with a novel Ni/SiO 2 magnetic catalyst, Catal.
Lett. 128 (2009) 465–474.
[33] C.I. Fernandes, M.D. Carvalho, L.P. Ferreira, C.D. Nunes, P.D. Vaz, Organometallic
Mo complex anchored to magnetic iron oxide nanoparticles as highly recyclable
epoxidation catalyst, J. Organomet. Chem. 760 (2014) 2–10.
[34] K. Bahrami, M. Khodamorady, Design of BNPs-TAPC palladium complex as a reu-
sable heterogeneous nanocatalyst for the O-arylation of phenols and N-arylation of
amines, Catal. Lett. 149 (2019) 688–698.
[17] N. Panda, A.K. Jena, S. Mohapatra, S.R. Rout, Copper ferrite nanoparticle-mediated
N-arylation of heterocycles: a ligand-free reaction, Tetrahedron Lett. 52 (2011)
1924–1927.
[35] X. Guo, H. Rao, H. Fu, Y. Jiang, Y. Zhao, An inexpensive and efficient copper cat-
alyst for N-arylation of amines, amides and nitrogen-containing heterocycles, Adv.
Synth. Catal. 348 (2006) 2197–2202.
[18] F. Pazoki, S. Bagheri, M. Shamsayei, M.J. Nejad, A. Heydari, BiPO4 decorated with
Ni–Fe layered double hydroxide as a highly efficient and reusable heterogeneous
catalyst for aldol condensation in green solvent, Mater. Chem. Phys. (2020)
123327.
[36] Y.-H. Liu, C. Chen, L.-M. Yang, Diazabutadiene: a simple and efficient ligand for
copper-catalyzed N-arylation of aromatic amines, Tetrahedron Lett. 47 (2006)
9275–9278.
[19] M.K. Miraki, J.A. Mehraban, E. Yazdani, A. Heydari, Deep eutectic solvent (DES) as
dual solvent/catalyst for synthesis of α-diazocarbonyl compounds using aldol-type
coupling, J. Mol. Liq. 234 (2017) 129–132.
[37] F. Nemati, A. Elhampour, Nano-magnetic Fe 3 O 4@ TiO 2/Cu 2 O composite: a
simple, effective and reusable heterogeneous catalyst for ligand-free N-arylation of
amines and nitrogen heterocycles, Res. Chem. Intermed. 42 (2016) 7611–7624.
[20] A.P. Abbott, D.L. Davies, G. Capper, R.K. Rasheed, V. Tambyrajah, Ionic liquids and
9