Efficient One Pot Synthesis of Phenylimidazo[1,2-a]pyridine Derivatives using Multifunctional Copper Catalyst Supported on β-Cyclodextrin Functionalized Magnetic Graphene oxide

Article abstract of DOI:10.1002/aoc.5913

In this paper, a novel, “green”, efficient and atom-economical methodology for the synthesis of N-(alkyl)-2-phenylimidazo[1,2-a]pyridin-3-amine derivatives based on copper catalyzed oxidative cyclization is presented. An efficient copper nanocatalyst was fabricated by immobilization of Cu on β-Cyclodextrin (βCD) functionalized magnetic graphene oxide nanosheets (denoted as Cu@βCD@MGO). This catalyst primarily oxidizes benzylic alcohols to aldehydes by aerobic O₂. The obtained aldehydes, in situ, takes part in a three component reaction with pyridin-2-amine and isocyanides to produce corresponding N-(alkyl)-2-phenylimidazo[1,2-a]pyridin-3-amine derivatives. The catalyst was characterized by TEM, SEM, VSM, FT-IR, XRD, TGA and ICP. As an advantage, the catalyst showed to be highly recoverable and no appreciable leaching was observed after 10 runs.

Full text of DOI:10.1002/aoc.5913

Received: 30 December 2019
DOI: 10.1002/aoc.5913
Revised: 5 June 2020
Accepted: 11 June 2020
F U L L P A P E R
Efficient One Pot Synthesis of Phenylimidazo[1,2-a]pyridine
Derivatives using Multifunctional Copper Catalyst
Supported on β-Cyclodextrin Functionalized Magnetic
Graphene oxide
Saeed Bahadorikhalili1
| Khodadad Malek2 | Mohammad Mahdavi3
1School of Chemistry, College of Science,
University of Tehran, 14155-6455, Tehran,
Iran
2Department of Chemistry, Isfahan
University of Technology, Isfahan,
84156-83111, Iran
3Endocrinology and Metabolism Research
Center, Endocrinology and Metabolism
Research Institute, Tehran University of
Medical Sciences, Tehran, Iran
In this paper, a novel, “green”, efficient and atom-economical methodology for
the synthesis of N-(alkyl)-2-phenylimidazo[1,2-a]pyridin-3-amine derivatives
based on copper catalyzed oxidative cyclization is presented. An efficient cop-
per nanocatalyst was fabricated by immobilization of Cu on β-Cyclodextrin
(βCD) functionalized magnetic graphene oxide nanosheets (denoted as
Cu@βCD@MGO). This catalyst primarily oxidizes benzylic alcohols to alde-
hydes by aerobic O2. The obtained aldehydes, in situ, takes part in a three com-
ponent reaction with pyridin-2-amine and isocyanides to produce
corresponding N-(alkyl)-2-phenylimidazo[1,2-a]pyridin-3-amine derivatives.
The catalyst was characterized by TEM, SEM, VSM, FT-IR, XRD, TGA and
ICP. As an advantage, the catalyst showed to be highly recoverable and no
appreciable leaching was observed after 10 runs.
Correspondence
Mohammad Mahdavi, Endocrinology and
Metabolism Research Center,
Endocrinology and Metabolism Research
Institute, Tehran University of Medical
Sciences, Tehran, Iran.
K E Y W O R D S
Email: momahdavi@sina.tums.ac.ir
copper nanocatalyst, magnetic grapheneoxide, multifunctional catalyst, aerobic oxidation,
phenylimidazopyridine
1 | INTRODUCTION
solid supports. By this approach, the advantage of both
homogeneous and heterogeneous catalysts could be
An interesting goal in clean chemistry is the development
of simple synthetic methods to provide new and
improved catalysts.[1–6] A large number of transition
metals show catalytic activity in different transforma-
tions, while among them, copper is of importance in
modern organic synthesis.[7–15] Due to the high activity
and selectivity, copper catalysts have also found wide
applications in several transformations such as oxidation
of alcohols,[16–18] synthesis of aryl cyanides,[19,20] oxida-
tion of carbonyl groups,[21–23] carbon-heteroatom bond
formation[24,25] and 1,3-dipolar cycloaddition.[26–28]
obtained to overcome the drawbacks of homogeneous
transition metal catalysts.[29–33] Graphene oxide (GO) is a
one-atom-thick two-dimensional sheet having honey-
comb sp2-bonded carbon. GO has attracted a great deal of
interest for different potential utilizations in theoretical
and experimental studies in catalysis, electronics, and
material sciences.[34–36] Magnetic graphene oxide (MGO),
one of the hottest materials in chemistry and material sci-
ences, has been studied extensively due to its fantastic
thermal, mechanical, and chemical properties and its
unique potential technical applications.[37–42] Its remark-
able characteristics such as numerous oxygen-containing
groups (e.g., –OH, –COOH, and epoxy), and extremely
high surface areas amenable to ligand conjugation and
An important issue, which has attracted great inter-
ests among researchers, is the catalyst recovery. A useful
strategy is immobilization of transition metal catalysts on
Appl Organomet Chem. 2020;e5913.
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https://doi.org/10.1002/aoc.5913

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BAHADORIKHALILI ET AL.
other manipulations enable it to be a promising candi-
date as
a brilliant support to immobilize metal
nanoparticles (NPs) for applying in catalyst development.
Among several ligands for coordination to transition
metals, β-cyclodextrin is of high interest for its unique
properties. Cyclodextrins are cyclic oligosaccharides of D
(+)-glucopyranosyl units linked by α-1,4-glycosidic bonds
and consist of a hydrophilic outer surface and a hydro-
phobic central cavity.[43,44] Cyclodextrins can include
water-insoluble organic materials into the cavity in aque-
ous solution and therefore is applied in phase transfer
and interface reaction catalyst.[45,46] Therefore, complexa-
tion with cyclodextrin is well-known as an effective
method for enhancing dissolution properties of poorly
soluble organic materials. In addition, β-cyclodextrin
showed to be an appropriate ligand for copper to be
applied in a 1,3-dipolar cycloaddition.[47] β-cyclodextrin
is used as ligand for several metallic catalysts, including
palladium,[48] copper[49] and non-metallic catalysis pro-
cesses as well.[50]
Phenylimidazo[1,2-a]pyridine derivatives, are signifi-
cant class of organic compounds and regardinig its struc-
ture, multicomponent reactions have been extended for
the synthesis of this class of compounds.[51–54] We have
reciently applied several nanoparticles, including super-
paramagnetic iron oxide mamoparticles, graphene oxide
and mesoporous silica nanoparticles.[55–59] Among sev-
eral nanopartices, which have been used as support for
the catalysts, magnetic graphene oxide showed an advan-
tageous benefits in the catalytic processes. For the fabri-
cation of more efficient immobilized catalysts,
β-cyclodextrin has been used as ligand in our previously
published papers.[60–63] Considering the interests of the
synthesis of imidazo[1,2-a]pyridine, in this work we
focused on using Cu@ΒCD@MGO as a catalyst. For this
purpose, we conducted oxidative, one-pot, mul-
ticomponent reaction of benzyl alcohol, isicyanides and
pyridin-2-amine derivatives. Regarding our previous
efforts on extending methodologies based on transition
metal catalyzed reactions,[64–66] herein, we report a prom-
ising cyclization reaction methodology via aerobic alco-
hol oxidation using Cu catalyst decorated on
polyethyleneimine modified magnetic graphene oxide to
obtain corresponding N-methyl-2-phenylimidazo[1,2-a]
pyridin-3-amine (4a-j) (Scheme 1).
SCHEME 1 Synthesis of N-(alkyl)-2-phenylimidazo[1,2-a]
pyridin-3-amine derivatives (4a-j)
a previously report methods.[66] Afterwards, the magnetic
graphene oxide (MGO) was manufactured from obtained
GO nanosheets. MGO was synthesized by the addition of
GO to a mixture containing magnetic iron oxide
nanoparticles, followed by ultrasonic irradiation. Then
MGO was functionalized by βCD via the covalent grafting
using βCD–silane obtained from the treatment of βCD
and TESPIC. The βCD@MGO was used as a dispersible
pendant for immobilizing Cu nanoparticles on the sur-
face of MGO nanosheets. Therefore, as synthesized
ΒCD@MGO was reacted with CuCl2 to provide
Cu@βCD@MGO as the designed catalyst (Scheme 2).
The structure of the nanocatalyst was characterized by
diverse techniques including transmission electron
microscopy (TEM), scanning electron microscopy (SEM),
vibrating sample magnetometer (VSM), Fourier trans-
form infrared spectroscopy (FT-IR), N2 adsorption–
desorp cvtion analysis, and inductively couple plasma-
atomic emission spectrometry (ICP-AES) analysis. ICP
was applied for determining the leaching of the copper
after the reaction completion.
The structures of obtained nanosheets were character-
ized by TEM and SEM (Figure 1). The introduction of
iron oxides with mean particle size of 20–25 nm onto the
graphene oxide nanosheets was evident from TEM and
SEM results. Iron oxide nanoparticles can be seen as dark
spots within the graphene oxide nanosheets. As can be
seen in Figure 1, the formation of magnetic iron oxide
nanoparticles on the graphene oxide nanosheets can be
clearly seen.
The magnetic behavior of the nanocatalyst was evalu-
ated by VSM technique. The magnetic hysteresis assessed
by VSM in an applied magnetic field at r.t. with the field
sweeping from −8,000 to +8,000 Oe can be observed in
Figure
2.
The
superparamagnetic
nature
of
2 | RESULTS AND DISCUSSION
Cu@βCD@MGO has been shown by its S-type magneti-
zation hysteresis loop. We note that the catalyst is mag-
netically recoverable. After the reaction completion, the
catalyst was separated from the reaction mixture by an
external magnet and reused in the next run without any
additional process. For proving the presence of copper in
The designed Cu catalyst is fabricated by immobilization
of copper on βCD modified magnetic graphene oxide. For
this purpose, initially, superparamagnetic graphene oxide
nanosheets were synthesized and confirmed according to

BAHADORIKHALILI ET AL.
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SCHEME 2 The synthesis of Cu@βCD@MGO nanocatalyst
the structure of the catalyst, EDX analysis was applied.
The EDX results are presented in Figure 2b. EDX results
clearly proves the presence of Cu in the strusture of
Cu@βCD@MGO catalyst.
the presence of iron oxide and graphene oxide
nanosheets.
It is believed that the immobilization of pincer-like
βCD pendant on the surface of MGO provides a good dis-
tribution of catalytically active Cu species on the support
and accordingly it stabilizes Cu during the chemical reac-
tion, and also prevents the aggregation of Cu
nanoparticles. Moreover, the Cu content of the obtained
solid catalyst was 0.25 mmol per gram of
[Cu@βCD@MGO] catalyst using ICP-AES (0.016 wt%).
The structure of the catalyst was studied by XRD
FT-IR spectroscopy was applied to prove the cova-
lent attachment of βCD to the MGO. In the IR spec-
trum of GO, the strong bands at 3430 and 1,246 cm−1
are attributed to the stretching and bending of the O–H
bond, respectively. The C=O bond in carboxylic acid
(or carbonyl moieties) and aromatic C=C bond in
unoxidized graphitic domains bands appeared at 1725
and 1,630 cm−1 respectively. The peak at 1365 cm−1
can be attributed to the bending absorption of carboxyl
group O=C–O. The existence of Fe3O4 is confirmed by
the appearance of the vibration band of Fe–O around
572 cm−1, in the FTIR spectrum of MGO. The appear-
ance of such bands in FTIR spectrum of βCD@MGO is
in agreement with the attachment of βCD to the MGO.
The bands at 3430 cm−1 are due to the O–H groups of
βCD attached to the surface, and the band at
1691 cm−1 assigned to the C=O. FT-IR spectra of the
nanocatalyst showed characterization peaks for Fe–O–
Fe, C=O and O–H groups (Figure 3), which indicates
method. Figure
4
shows the XRD patterns of
Cu@βCD@MGO. The diffraction pattern matches the
desired structure of copper supported magnetic graphene
oxide. In the diffraction pattern in Figure 4, an intense
peaks at 2θ = 11.4ꢀ could be assigned to the reflection of
the 001 plates of graphene oxide. In addition, the peaks
at 2θ = 30.3ꢀ (220), 35.7ꢀ (311), 43.5ꢀ (400), 53.9ꢀ (422),
57.5ꢀ (511) and 63.0ꢀ (440) could be correlated to the
standard XRD data of magnetic iron oxide nanoparticles.
It should be noted that, the diffraction peak at 2θ = 11.4ꢀ
of graphene oxide is disappeared. This observation can be
due to the covering up the weak carbon peaks by iron

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BAHADORIKHALILI ET AL.
FIGURE 1 SEM (Top) and
TEM images (Bottom) of
Cu@βCD@MGO
oxides after functionalizing the graphene oxide by super-
paramagnetic iron oxide nanoparticles.[67,68]
(Scheme 1). The reaction was studied for finding the opti-
mized conditions. Several factors, which affect the reac-
tion performance, and therefore the yield of the reaction,
were optimized. For this purpose, only one variable was
changed and all the other variables were remained con-
stant to see the effect of the studied variable on the reac-
tion performance. Blank runs showed the lack of
catalytic activity in the presence of MGO or βCD@MGO.
To find the optimal condition, the reaction between
benzyl alcohol, pyridin-2-amine and cyclohexyl
isocyanide was selected as a model reaction and was per-
formed under different conditions. Performing the reac-
tion in the presence of different amounts of the catalyst
proved that, the high amounts of the products are formed
The functionalization content in Cu@βCD@MGO
catalyst was evaluated by thermogravimetric analysis
(TGA) TGA result of Cu@βCD@MGO catalyst is pres-
ented in Figure 5. It could be observed that a weight loss
ꢀ
is occurred in 100 C, which could be correlated to the
evaporation of the adsorbed water. The weight loss in
higher temperatures are due to the decomposition of the
organic moieties in the structure of the catalyst.
The activity of the catalyst was subsequently investi-
gated upon characterization in the C-O oxidation
followed by multicomponent reaction between the pro-
duced aldehydes, pyridin-2-amine and isocyanides

BAHADORIKHALILI ET AL.
5 of 12
FIGURE 2 VSM (a) and EDX (b) result of
Cu@βCD@MGO
FIGURE 5 TGA curve of Cu@βCD@MGO catalyst
FIGURE 3 FTIR spectra for magnetic graphene oxide and
Cu@βCD@MGO
presence of the catalyst is essential for the reaction per-
formance. It could be observed that no products was
observed when the reaction as performed without the
catalyst. Moreover, a reaction was performed and the cat-
alyst was separated after 4 hr. The reaction was
when 25 mg of the catalyst (0.5 mol%) is used for each
mmol of the substrates after 12 hr. The results are pres-
ented in Table 1. According to the results of Table 1, the
FIGURE 4 XRD pattern of
Cu@βCD@MGO catalyst

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BAHADORIKHALILI ET AL.
TABLE 1 Effect of the amount of catalyst on the isolated
amine derivatives were obtained in moderꢀate to good
yields for various examined substrates at 70 C. As illus-
trated, a wide range of products can be efficiently pro-
duced with this catalytic system. All substrates possessing
electron-rich as well as electron-poor substituents under-
yield[a]
Entry
Catalyst (mol%)
Isolated Yield (%)
1
2
3
4
5
6
7
8
9
0.00
0.12
0.25
0.37
0.50
0.75
1.25
1.50
2.00
0
17
40
62
73
73
74
74
74
went
the
cyclization
reaction
catalyzed
by
Cu@βCD@MGO.
A great advantage of Cu@βCD@MGO is its reusabil-
ity. The separation of the catalyst from the reaction mix-
ture could simply be done by using an external magnet.
For evaluating the reusability of the catalyst, the reaction
of 4-methylbenzyl alcohol, cyclohexyl isocyanide and
pyridin-2-amine was selected as the model reaction. The
reusability study was performed under the optimized
reaction conditions. After the reaction completion, the
catalyst was separated by a magnet and in the next
reaction. The reaction was repeated for 10 runs and no
decrease in the reaction performance was observed
(Figure 6).
aCondition: 2-chlorobenzyl alcohol (1 mmol), pyridin-2-amine
(1 mmol), and cyclohexyl isocyanide (1 mmol) in EtOH at 70 ꢀC for
24 hr.
continued without the catalyst up to 12 hr. The perfor-
mance of the reaction was followed by GC analysts. The
results showed that after the removal of the catalyst, the
reaction has not been completed.
Finally, we performed the reaction in various sol-
vents. Table 2 shows that the product formation is
observed in all the tested solvents, however the best
results were observed for the reactions which have been
carried out in DMSO or EtOH as solvent. Regarding the
advantages of ethanol, such as environmental friendly,
low toxicity, facile work up and lower cost in comparison
with DMSO, ethanol was selected as the best solvent for
the reaction.
For studying the stability of the catalyst in the reac-
tion conditions, the structure of Cu@βCD@MGO was
evaluated after recovery of the catalyst by several
methods, including VSM, TGA, and ICP analysis. The
results of TGA and VSM analyses of Cu@βCD@MGO
catalyst after 5th cycle of recovery is presented in
Figure 7a and b, respectively. It could be observed that,
the characters and the properties of the catalyst has not
been changed in the reaction conditions. For studying
possible leaching of copper from the catalyst,
Cu@βCD@MGO was recovered from the reaction mix-
ture after the reaction completion after first and fifth
cycles. The solution was analyzed by ICP-AES and no
copper was observed, which proves the stability of the
catalyst in the reaction conditions. This catalyst is promi-
nent due to the efficient recoverability and high turnover
number (TON). The robust catalyst achieved cumulative
TONs of about 1,500 over 10 successive runs. The cumu-
lative TON is obtained by the sum of the values for the
TONs for all examined runs. In addition, the catalyst was
added to the reaction solvent and stirred under the reac-
tion conditions. After 24 h, the catalyst was separated
and the solution as characterized for any possibly
leaching by ICP analysis. ICP results proved no leaching
of the catalyst, which shows the stability of
Cu@βCD@MGO under the reaction conditions.
We investigated the scope of the Cu catalyzed oxida-
tive cyclization reactions between benzyl alcohol,
pyridin-2-amine, and isocyanides (4a-j) under the opti-
mized conditions. As shown in Table 3, the
corresponding N-alkyl-2-phenylimidazo[1,2-a]pyridin-3-
TABLE 2 Effect of different solvents on the reaction time and
the isolated yield[a]
Entry
Solvent
H2O
Time (hr)
Isolated Yield (%)
1
2
3
4
5
6
7
47
36
36
12
48
48
48
41
56
67
73
48
55
41
DMF
Regarding the good performance of the reaction in
the presence of Cu@βCD@MGO, a possible mechanism
was proposed, which is presented in Scheme 3. As can be
seen, at the beginning of the reaction, an aerobic oxida-
tion of benzyl alcohol to the corresponding albehyde
takes place in the presence of Cu@βCD@MGO catalyst.
The great advantage of this step is that the oxidation reac-
tion occurs in the presence of the oxygen in the air and
DMSO
EtOH
EtOH
CH2Cl2
CH3CN
aCondition: 2-chlorobenzyl alcohol (1 mmol), pyridin-2-amine
(1 mmol), and cyclohexyl isocyanide (1 mmol) at 70 ꢀC.

BAHADORIKHALILI ET AL.
7 of 12
TABLE 3 Substrate scope exploration[a]
aCondition: alcohol (1 mmol), pyridin-2-amine (1 mmol), isocyanide (1 mmol), and Cu@βCD@MGO (0.50 mol%) in ethanol at 70 ꢀC for
12 hr.
FIGURE 6 reusability of Cu@βCD@MGO
catalyst after 10 sequential runs

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BAHADORIKHALILI ET AL.
FIGURE 7 (a) TGA curve;
and (b) VSM result of
Cu@βCD@MGO after 5th cycle
of the recovery of the catalyst
SCHEME 3 Proposed mechanism for
Cu@βCD@MGO catalyzed synthesis of
phenylimidazo[1,2-a]pyridine derivatives
there is no need to any other oxidizing reagent. The
fabricated aldehyde, reacts to pyridin-2-amine and forms
1-phenyl-N-(pyridin-2-yl)methanimine (5) the reaction of
1-phenyl-N-(pyridin-2-yl)methanimine with isocyanide
derivative leads to the formation of N-(2-(alkylimino)-
1-phenylethyl)pyridin-2-amine (6). An intramolecular

BAHADORIKHALILI ET AL.
9 of 12
cyclization reaction takes place in N-(2-(alkylimino)-
1-phenylethyl)pyridin-2-amine, which gives 3-(alkyli
mino)-2-phenyl-2,3-dihydro-1H-imidazo[1,2-a]pyridin-4-
ium (7). The desired phenylimidazo[1,2-a]pyridine will
be formed by a 1,3-H shift in compound (7).
A comparison between the current method and
previously reported methods for the synthesis of
phenylimidazo[1,2-a]pyridine derivatives showed the
good activity and high performance of Cu@βCD@MGO
catalyst for the synthesis of the mentioned compounds.
In most cases, the use of non-reusable catalysts limit
industrial production of these compounds.[51] In addition,
using toxic[51] or high temperature conditions are of other
drawbacks of some of previous reports.[69] In this work,
the reaction was performed in ethanol as a green and
nontoxic solvent. In addition alcohols were oxidized by
aerobic oxygen.
(s), doublet (d), triplet (t), multiplet (m) and doublets of
doublet (dd) are recorded. Mass spectra were recorded on
an Agilent Technology (HP) mass spectrometer operating
at an ionization potential of 70 eV. The elemental analy-
sis was performed with an Elemetar Analysen system
GmbH VarioEL CHNS mode. Purification of all product
were conducted by column chromatography on silica gel
using petroleum ether and ethyl acetate as eluent. Thin
layer chromatography was carried out on silica gel
254 analytical sheets obtained from Fluka. Column chro-
matography was carried out on the column of silica gel
60 Merck (230–240 mesh) in glass columns (2 or 3 cm
diameter) using 15–30 grams of silica gel per one gram of
the crude mixture. Transition electron microscope images
were recorded on a HITACHI S-4160. Thermogravimetric
analysis of the samples were recorded by TGA Q50 V6.3
Build 189 instrument.
3 | CONCLUSIONS
4.2 | Preparation of graphene oxide
In summary, we have introduced a novel methodology
for the facile synthesis of N-alkyl-2-phenylimidazo
[1,2-a]pyridin-3-amine based on Cu catalyzed C-O oxi-
dation followed by multicomponent cyclization reac-
The GO was manufactured from graphite using modified
Hummer's method according to our previous report.[66]
Briefly, 1 g of graphite powder was added to a continuous
stirring solution of 50 mL H2SO4 98% in an ice bath and
then, 2 g KMnO4 was gently added to it. It should be
noted that the rate of addition was carefully controlled to
avoid a sudden increase of mixture temperature. The
reaction mixture was left to stir for 2 hr at temperatures
below 10 ꢀC, and followed by another 1 hr at 35 ꢀC. Then
the reaction mixture was diluted with 50 ml of deionized
water (DWꢀ) in an ice bath and the temperature was kept
below 100 C. After 1 hr of stirring, the mixture was fur-
ther diluted to 150 ml with DW. Then, 10 ml of H2O2
30% was added to the mixture which changing its color
to brilliant yellow. The resulting solid was separated by
centrifuge and washed thoroughly with 5% HCl
aq. solution and DW to neutralize. Finally it was dried at
60 ꢀC for 24 hr.
tions.
A novel and efficient Cu containing βCD
modified magnetite graphene oxide, Cu@βCD@MGO
has been developed as highly active and stable
nanocatalyst for simultaneous C-O bond oxidation and
multicomponent
reactions.
The
transformation
proceeded well with a broad substrate scope under mild
conditions to achieve high to moderate isolated yields.
The salient features of the proposed method include
high efficiency, generality and simplicity which lead to
high yields, a cleaner reaction profile and easy recycla-
bility of the highly stable heterogeneous catalyst by a
simple magnet separation.
4 | EXPERIMENTAL
4.1 | General remarks
4.3 | Preparation of magnetic graphene
oxide (MGO)
Solvents, reagents and chemicals were obtained from
Merck (Germany) and Fluka (Switzerland) Chemical
Companies. Melting points were taken on a Kofler hot
stage apparatus and are uncorrected. The IR spectra were
obtained on a Nicolet Magna FT-IR 550 spectrophoto
meter (potassium bromide disks). Nuclear magnetic reso-
nance spectra were recorded on a Brucker Bruker FT-500
spectrometers using tetramethylsilane (TMS) as internal
standard in pure deuterated solvents. Chemical shifts are
given in the δ scale in parts per million (ppm) and singlet
The MGO nanosheets were synthesized by co-
precipitation of Fe3+ and Fe2+ in the presence of GO.[66]
The solution of Fe3+ and Fe2+ was prepared in a 2:1 mole
ratio. 500 mg of GO was dispersed in 40 mL of water by
sonication for 45 min. Then a 50 mL solution of FeCl3
(1 g) and FeCl2 (375 mg) in DW was added to the later
solution. The reaction temperature was raised to 85 C
and ammonia solution 30% was added to pH 10. After
45 min of vigorously stirring, the solution was cooled to
ꢀ

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BAHADORIKHALILI ET AL.
r.t., and finally the obtained black precipitate was cen-
trifuged at 6000 rpm for 10 min and washed thoroughly
with DW and dried at 60 ꢀC for 24 hr.
recrystallization from ethanol. The structure of all com-
pounds were confirmed by spectral data (1H and
13CNMR, FT-IR, mass spectroscopy) [See supplementary
information]. The recovered catalyst was rinsed with
water and EtOH, and finally dried at r.t. and reused with-
out any pretreatment for the next run. The recycling test
of the catalyst was performed in the reaction according to
the above procedure.
4.4 | Preparation of ΒCD
functionalized MGO
βCD-Silane was synthesized via the hydrogen-transfer
nucleophilic addition reaction between the end hydroxyl
group of βCD and 3-(triethoxysilyl)propyl isocyanate
(TESPIC). 10 mmol of βCD was dissolved into 50 ml of
dry pyridine ꢀwith vigorous stirring under argon atmo-
sphere at 70 C. After stirring for 6 hr, 10 mmol of TES-
PIC was added into the later solution. After 24 h, the
solvent was removed by vacuum evaporation. The resi-
due was washed three times with n-hexane, and then rec-
rystallized from EtOH.
1.1 | Recovery of cu@βCD@MGO catalyst
For studying the reusability of the catalyst, the reac-
tion of 4-methylbenzyl alcohol, cyclohexyl isocyanide
and pyridin-2-amine was selected as the model reac-
tion. After the reaction was completed, the catalyst
was separated from the reaction mixture by using an
external magnet. The catalyst was used in the next
reaction and this process was repeated for 10 times.
Each reaction was performed in the optimal condi-
tions, including 4-methylbenzyl alcohol (1 mmol),
cyclohexyl isocyanide (1 mmol), pyridin-2-amine
(1 mmol), and Cu@βCD@MGO (0.50 mol%) in ethanol
for 12 hr.
Then a solution of 1 g of βCD–silane in 30 ml of EtOH
was added drop-wise to a vigorous stirring solution of
250 mg of MGO in 30 ml EtOH/H2O (1:2) and HCl
(pH = 4). After vigorous stirring for 24 hr, the solution
was magnetically separated and washed thoroughly with
ꢀ
EtOH. The white residue was dried at 100 C in vacuum
for 12 hr to obtain βCD@MGO.
ORCID
Saeed Bahadorikhalili https://orcid.org/0000-0001-
8047-342X
Mohammad Mahdavi https://orcid.org/0000-0002-
4.5 | Preparation of cu@ΒCD@MGO
catalyst
8007-2543
To a mixture of βCD@MGO (1 g) in 50 ml dry
CH2Cl2, CuCl2 (2 mmol) was added and stirred at
room temperature under argon atmosphere for 24 hr.
The obtained solid was magnetically separated and
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washed with CH2Cl2 (2
×
10 ml) and Et2O
(2 10 ml). Cu@βCD@MGO nanocatalyst was
×
obtained as a dark black powder after drying under
vacuum for 12 hr.
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4.6 | General procedure for
cu@βCD@MGO catalyzed synthesis of N-
alkyl-2-phenylimidazo[1,2-a]pyridin-
3-amines
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the catalyst was separated using an external magnet. The
solvent was evaporated and the products were purified by

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BAHADORIKHALILI ET AL.
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: Bahadorikhalili S,
Malek K, Mahdavi M. Efficient One Pot Synthesis
of Phenylimidazo[1,2-a]pyridine Derivatives using
Multifunctional Copper Catalyst Supported on
β-Cyclodextrin Functionalized Magnetic Graphene
oxide. Appl Organomet Chem. 2020;e5913. https://
doi.org/10.1002/aoc.5913