One-step synthesis of magnetically recyclable palladium loaded magnesium ferrite nanoparticles: application in synthesis of anticancer drug PCI-32765

Article abstract of DOI:10.1080/24701556.2020.1724147

Novel Palladium nanoparticles supported nano Magnesium ferrite catalyst (Pd/MgFe₂O₄) was synthesized by one-step ultrasound assisted coprecipitation. In-situ formed by-products assisted salt cage calcination approach was employed to

Full text of DOI:10.1080/24701556.2020.1724147

Inorganic and Nano-Metal Chemistry
ISSN: 2470-1556 (Print) 2470-1564 (Online) Journal homepage: https://www.tandfonline.com/loi/lsrt21
One-step synthesis of magnetically recyclable
palladium loaded magnesium ferrite
nanoparticles: application in synthesis of
anticancer drug PCI-32765
Gopala Krishna Dasari, Satyaveni Sunkara & Purna Chandra Rao Gadupudi
To cite this article: Gopala Krishna Dasari, Satyaveni Sunkara & Purna Chandra Rao Gadupudi
(2020): One-step synthesis of magnetically recyclable palladium loaded magnesium ferrite
nanoparticles: application in synthesis of anticancer drug PCI-32765, Inorganic and Nano-Metal
Chemistry, DOI: 10.1080/24701556.2020.1724147
To link to this article: https://doi.org/10.1080/24701556.2020.1724147
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INORGANIC AND NANO-METAL CHEMISTRY
https://doi.org/10.1080/24701556.2020.1724147
One-step synthesis of magnetically recyclable palladium loaded magnesium
ferrite nanoparticles: application in synthesis of anticancer drug PCI-32765
Gopala Krishna Dasaria,b, Satyaveni Sunkaraa, and Purna Chandra Rao Gadupudia
b
aDepartment of Chemistry, Jawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, India; Chemical Research and
Development, Shilpa Medicare Limited, Vizianagaram, Andhra Pradesh, India
ABSTRACT
ARTICLE HISTORY
Received 8 September 2019
Accepted 22 January 2020
Novel Palladium nanoparticles supported nano Magnesium ferrite catalyst (Pd/MgFe2O4) was syn-
thesized by one-step ultrasound assisted coprecipitation. In-situ formed by-products assisted salt
cage calcination approach was employed to control the particle size by minimizing the risk of
nanoparticle aggregation during calcination. Palladium nanoparticles were grafted on the surface
of nanocrystalline MgFe2O4 without using any reducing agents, capping agents and surface modi-
fiers. The catalyst preparation method was having minimum process operations and can be used
for synthesis of various potential nanocatalytic systems. The catalyst was extensively characterized
by using various techniques SEM-EDS, TEM, FT-IR, XPS, XRD, VSM, BET, and ICP-AES. Pd/MgFe2O4
was magnetically separable and shown its potential utility for ligand less Suzuki-Miyaura coupling
reaction using green solvent system Water and Ethanol. The nanocatalyst shows consistent activity
and excellent reusability in the synthesis of Biaryls with excellent yields. In addition, the prepared
catalytic nanoparticles were successfully applied in the synthesis of 5-(4-phenoxyphenyl)-7H-pyr-
rolo[2,3-d]pyrimidin-4-ylamine an intermediate for preparing the marketed anticancer drug PCI-
KEYWORDS
One-step synthesis;
coprecipitation; salt cage
assisted calcination; Pd-
Magnesium ferrite;
magnetic nanoparticles;
Suzuki-Miyaura coupling
R
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32765 under the name IMBRUVICA (Ibrutinib-BTK inhibitor).
Introduction
Ferrites can be prepared by various techniques, such as
conventional coprecipitation, pyrolysis, solution combustion,
freege drying.[8] Fino et al.[9] synthesized AB2O4 (CoCr2O4,
MnCr2O4, MgFe2O4 and CoFe2O4 with high specific surface
by solution combustion synthesis using metal nitrates and
urea. Ultrasonic irradiation assisted co-precipitation was one
of the important tool for synthesis ferrites and their compo-
sites.[10] Senapati et al.[11] prepared the CoFe2O4–Cr2O3–SiO2
nanocomposite by using ultrasonic irradiation. Magnetic
nanomaterial, magnesium ferrite is a soft spinel[12] and pos-
sess large number of surface hydroxyl groups and Lewis
acidic Mg2þ sites of cubic spinel ferrite structure provides
effective interaction with active phase and with the reactants.
MgFe2O4 based catalysts shown considerable improvements
in their catalytic functionality due to the physiochemical
properties, surface interactions.[13] Magnetic nanomaterial
MgFe2O4 and its composites offers applications in various
fields such as biomedical applications, dye adsorption, mer-
Nanocatalysts are semi-heterogeneous catalysts which con-
sists of hybrid advantages of both heterogeneous as well as
homogenous catalysts. This is due to their structural and
morphological properties, along with enhanced recovery and
recyclability.[1] In the presence of magnetic field applied
externally the magnetic nanocatalytic systems provide easy
separation of the catalyst based on their intrinsic magnetic
properties.[2] The catalyst activity depends on various char-
acteristics such as particle size distribution, surface area,
morphology and active phase dispersion on catalyst support
phase. The combined physiochemical properties and elec-
tronic properties of the active phase and support material
greatly influence the functionality of the catalyst.[3]
Nano magnetic ferrites are act as very good catalysts and
also serve as excellent catalytic supports.[4] Ferrites have
shown tremendous catalytic applications such as transfer
hydrogenation, biodiesel synthesis, dye degradation,
Nitrophenol reduction, and b-lactams synthesis.[5] Ferrites
supported nano catalysts were highly stable, recyclable and
magnetically retrievable after completion of reactions. Saire-
Saire et al.[6] reported Au/CoFe2O4 for catalytic reduction of
4-nitrophenol and dimethylphenylsilane oxidation, Dutta
et al.[7] developed CoFe2O4@SiO2-SH-CuI, applied in the
synthesis of oxidative amidation.
cury measurement, Pertechnetate (99TcO4 ) removal, photo
-
catalysis, Hydrogen storage, Knoevenagel condensation, gas
sensors, electro chemistry.[14] Magnesium ferrite supported
catalysts and their nanocomposites are magnetically separable
and shown their applications in diverse fields CO-oxidation,
b-chloroacetates synthesis, vanillin production, Biomedical
applications, antibacterial study.[15]
CONTACT Gopala Krishna Dasari
Krishna.chemistry@yahoo.com
Department of Chemistry, Jawaharlal Nehru Technological University, Kakinada, Andhra
Pradesh 500085, India
Supplemental data for this article is available online at https://doi.org/10.1080/24701556.2020.1724147.
ß 2020 Taylor & Francis Group, LLC

2
G. K. DASARI ET AL.
Palladium is an industrially important active catalyst use- Microscopy with X-ray microanalysis was performed by
ful in the synthesis of pharmaceuticals, fine chemicals and
agrochemicals.[16] Palladium supported on magnetic ferrite
material is the most important heterogeneous catalyst as it
offers high surface area and easy separation.[17] Rathi
et al.[18] synthesized the Maghemite decorated with ultra-
small palladium nanoparticles (c-Fe2O3–Pd) by simple
coprecipitation method. The incorporation of active catalytic
species (Pd) during the synthesis of magnetic nanoparticles
provides easy access in preparation.[19] The magnetic nano-
palladium catalysts can be prepared by various chemical
modifications includes functionalization and surface modifi-
cation. However but most of the methods require several
conversions steps and involve usage of several toxic
chemicals.[20]
Most importantly Green Chemistry states the need for
environmentally benign and sustainable catalytic systems to
save ecological aspects. There is still a need for developing
simple, efficient methods to synthesize palladium nanocata-
lysts and their applicability in potential industrial processes.
Herein we report an efficient and successful loading of palla-
dium nanoparticles on magnetic ferrite during the synthesis
itself. The catalyst was prepared by one-step ultrasound
assisted co-precipitation method, and salt cage assisted calcin-
ation to minimize the risk of aggregation and controlled par-
ticle size.[21] The catalyst preparation was designed to
improve the distribution of active catalytic phase over the
catalyst support phase, by using the metal precursors directly
and nanocrystal growth was controlled by using the with in-
situ formed by-products aided calcination. This one-step
co-precipitation method provides easy access for catalyst syn-
thesis. It minimizes the addition of multiple reagents and
number of steps which will save energy, time and reduces
effluent. Proposed facile approach promises a wide range of
applications and could be useful for preparation of various
potential nano catalytic systems with good dispersion, con-
trolled particle size. Magnesium and iron are very less toxic
to humans and the environment. According to ICH-Q3D
guidelines these metal impurities were having low inherent
toxicity than class-3 elements,[22] MgFe2O4 based catalysts
have advantages over more toxic Ni, Co based ferrites espe-
cially in pharmaceutical applications. Pd/MgFe2O4 nanocata-
lyst was applied for Suzuki cross coupling reactions and
synthesis of an intermediate for preparing marketed anti-
SEM-EDS, JEOL JSM-7600F, at operating voltage range 0.1
to 30 kV. Transmission electron microscopy TEM-PHILIPS.
CM 200, operating voltage range 20-200kV was used to
examine the morphology, SAED pattern, and size of the
nanoparticles. Powder X-ray diffraction pattern was exam-
ined by using XPert Pro (PANalytical) using Cu Ka radi-
ation (k ¼ 1.5406 Aꢀ) with scanning rate 2 degree per
minute to investigate the crystal structure and size of the
nanoparticles. Inductively coupled plasma atomic emission
spectroscopy ICP-AES-ARCOS 1.6 kW, 27.12 MHz was used
to obtain the palladium content in samples. To record the
NMR spectra of products NMR- VARIAN, USA, Mercury
plus 300 MHz NMR Spectrometer, 5 mm Auto switchable
probe with PFG was used. FT-IR spectra were obtained by
using Agilantcary 300. The XPS analysis was carried out
using X-ray Photoelectron Spectroscopy (XPS) with Auger
Electron Spectroscopy (AES) Module Model: PHI 5000
Versa Prob II,FEI Inc. Surface area and Porosity analyzer
(Gemini VII-2390t) was used to measure the BET surface
area of the sample. The magnetic moment of the sample
was analyzed with Lakeshore 7410S Vibrating Sample
Magnetometer (VSM) 3.42 Tesla (Electromagnet)
Sensitivity: 10-7 emu, Low Temperature range 15-300 K.
ꢁ
Synthesis of palladium loaded magnesium ferrite (Pd/
MgFe2O4) nanoparticles
Magnesium ferrite nanoparticles were loaded with palladium
during their synthesis by ultrasound assisted co-precipitation
method. In a 500 ml glass beaker containing 100 ml double
distilled demineralized water, added FeCl3(10 mmol), and
MgCl2 (5 mmol). The reaction mixture was placed in an
ultrasonicator (Bio-technics, BTI-48, frequency 33kHz, power
250 W) and added PdCl2 150 mg, sonicated for 10min (clear
solution observed). The reaction mixture pH was adjusted to
12 using 1 N aqueous NaOH solution (orange precipitate was
observed). The reaction mixture was slowly evaporated to
dryness at 120 ꢀC. The obtained material was calcinated at
300 ꢀC for about 4 h along with in-situ formed sodium chlor-
ide salts. Obtained cake was distributed in water, separated by
centrifugation, washed with excess water, ethanol and then
oven dried at 100 ꢀC overnight under nitrogen atmosphere
(flow rate 30ml/min). The obtained catalyst was stored in a
glass vial. The catalyst was reproduced by the above proced-
ure. In this process, the salts obtained by adjustment of pH
in the reaction mixture may surround the nanoparticles dur-
ing calcination. Thus the nanocrystal growth was controlled.
The catalyst obtained as a fine powder after calcination, fur-
ther grinding was not required. The prepared Pd-Magnesium
ferrite nanocatalyst was denoted as Pd/MgFe2O4.
R
V
cancer drug PCI-32765, under the name of IMBRUVICA
via Suzuki coupling.[23]
Experimental
Materials and instruments
Iron(III)chloride (FeCl3), Magnesium(II)chloride (MgCl2)
and Sodium Hydroxide were purchased from Fischer
Scientific. Palladium chloride (PdCl2) was purchased from
Aldrich. Ethanol was purchased from Merck. All the chemi-
cals were of analytical grade.
Results and discussion
Synthesis and characterization of Pd/MgFe2O4
The prepared catalyst Pd/MgFe2O4 was characterized by
various techniques such as SEM-EDS, TEM, ICP-AES, FT-
Magnesium ferrite was loaded with palladium by simple co-
IR, XPS, VSM, BET and XRD. Scanning Electron precipitation of metal precursors, represented as

INORGANIC AND NANO-METAL CHEMISTRY
3
Figure 1. XPS spectra of Pd/MgFe2O4.
PdxMgFe2O4(palladium weight%, x ¼ 1). The catalyst manu- corresponding elements XPS screening results of Fe 2p, Mg
facturing process involves the utilization of in-situ formed 2p and O 1S. The presence of XPS (Figure 1) characteristic
sodium salts as a salt cage for nanoparticles. These Sodium peak at regions 335 eV and 342 eV for Pd(0) indicates that
chloride salts obtained by adjustment of pH in the reaction the majority amount of palladium was adsorbed on the sur-
mixture were surrounding the palladium loaded Magnesium face of MgFe2O4 as palladium (0) nanoparticles.[17] The XPS
ferrite nanoparticles during calcination. Upon dispersion of peck position for Pd(OH)2 and PdO were in the region
calcinated cake in water, the surrounded sodium chloride 336.80 eV, so Pd(OH)2 and/or PdO might be also present
19
salts were dissolved in water; Pd/MgFe2O4 was simply sepa- along with palladium nanoparticles.
The palladium con-
rated by application magnetic field. The catalyst obtained as tent measured by XPS analysis was 1.24 wt%. And the palla-
fine powder, further grinding was not required. Thus, the dium content measured by ICP-AES was 1.20 wt %.
nanocrystal growth was controlled by salt cage.
Conventional Pd/MFe2O4(M ¼ Co, Ni, Zn) catalyst prepar- SEM-EDS and shown in Figure 2. The elemental distribution
ation methods required multiple process operations such as of Pd/MgFe2O4 was Mg
13.00%, Fe 24.15%,
The elemental analysis of Pd/MgFe2O4 was studied by
¼
¼
collecting the precipitate by centrifugation leaving sodium O ¼ 62.43%, and Pd ¼ 0.41%. The atomic ratio of Fe to Mg
salts in mother liquors, loading of active catalytic phase, cal- obtained was 0.54. The palladium weight % obtained from
cination and grinding the obtained calcinated cake. The Pd/ EDS analysis was 1.33%.
XRD analysis (Figure 3) showed peaks at 2h ¼ 29.79ꢀ,
MgFe2O4 catalyst preparation method was advantageous in
terms of minimizing process operations, reducing the
35.44ꢀ, 43.04ꢀ, 53.42ꢀ, 57.42ꢀ, 62.71ꢀ which represent the
Braggs reflections from the (220), (311), (400), (422), (511),
(440), respectively. The ‘d’ spacing values observed were
2.99, 2.53, 2.099, 1.714, 1.614 and 1.481. The crystalline data
matches with the JCPDS Card No. (#89-4924). Palladium
peaks were observed at 2h values 40ꢀ, 46ꢀ. The data
agglomerization risk, simplicity and industrially viability for
large scale synthesis of nanocatalysts toward industrially
important catalytic transformations. It provides high surface
area, thereby the number of active sites was increased, and
resulting in enhanced catalytic activity.
The active catalytic phase palladium was distributed by obtained from TEM, SAED pattern (Figures 4 and 5) were
forming ultra fine nanoparticles <6nm upon the magnesium in agreement with XRD analysis. Based on the XRD pat-
ferrite phase. The Palldium chloride (PdCl2) was converted terns, the plane corresponding to the most intense peak 2h
into palladium hydroxide (Pd(OH)2) colloids and dispersed value 35.44ꢀ was (311). The average crystallite domain sizes
on the ferrite nanoparticles under basic conditions. The col- (D) of particles have been calculated from XRD peaks using
loidal Pd(OH)2 are further converted into PdO or Pd(0) Scherrer’s equation: D ¼ k/(DW Cosh), where k is wave-
nanoparticles in presence of aqueous NaOH at basic pH via length of X-ray, h is the Bragg’s diffraction angle in radians,
reduction of Pd(II); and during workup with ethanol. The and DW is the true half-peak width of the XRD lines. The
support phase magnesium ferrite was attributed by the average crystallite (grain) size was 6.4 nm obtained by XRD

4
G. K. DASARI ET AL.
data, 8.5 nm from TEM analysis (particle size 5-18 nm). The
The magnetic properties of the nanocrystalline Pd/
grain size obtained from XRD analysis was lower than the MgFe2O4 were measured as a function of the field and tem-
particle size from TEM analysis.
perature. Figure 9 shows the magnetization curves of the
Pd/MgFe2O4 nanoparticles. The saturation magnetization
(Ms) obtained was 19.65 emu/g. The magnetization slightly
decreased in comparison with bulk sample due to weak
bonding of magnetic spins at the surface of nanocrystal-
line MgFe2O4.
Figure 5 shows that the Pd/MgFe2O4 nanoparticles are
crystalline, having size below 20 nm with random distribu-
tion in 5-18nm range. The dispersion of palladium was con-
firmed by EDS element mapping analysis. Further the Pd
nanoparticles (black dots, size < 6 nm) are of lower size
than nanocrystalline magnesium ferrite.
Figure 6 represents the EDS elemental mapping of Fe,
Mg, O and Pd. The TEM image analysis (Figure 5) and
SEM-EDS elemental dot mapping (Figure 6) clearly repre-
senting the palladium active phase was well distributed along
with the catalyst support (nano magnesium ferrite). The
histogram (Figure 7) reveals that the magnesium ferrite
nanoparticles size ranging from 5 nm to 18 nm with an aver-
age size of 8.5 nm. The palladium nanoparticles are having
lower particle size than Magnesium ferrite nanocrystal. The
FT-IR spectrum shown in Figure 8, indicates the presence of
OH groups (3450 cmꢂ1) on the surface of magnesium fer-
rite, and 576 cmꢂ1 and 434 cmꢂ1 bands indicates tetrahedral
and octahedral intrinsic stretching vibrations of Fe-O.[24]
The nitrogen adsorption–desorption isotherms of Pd/
MgFe2O4 NPs were studied using Brunauer-Emmett-Teller
(BET) method at temperature 77.35 K (Figure 10). The BET
surface area for Pd/MgFe2O4 was found to be 31.28 m2 gꢂ1
.
The higher surface area of MgFe2O4 NPs can be attributed
to the decrease in size of the crystallite. The average pore
diameter of Pd/MgFe2O4 was calculated by using Barret-
Joyner-Halenda (BJH) method and found to be 3.04 nm.
The average pore diameters obtained from ferrite NPs are
due to the intra-granular pore formed within the
metal oxides.
Figure 2. SEM-EDS of Pd/MgFe2O4.
Figure 4. TEM-SAED pattern of Pd/MgFe2O4.
Figure 3. XRD pattern of Pd/MgFe2O4.

INORGANIC AND NANO-METAL CHEMISTRY
5
Figure 5. TEM-Imaging of Pd/MgFe2O4 at different magnifications.
Figure 6. SEM-EDS, Elemental mapping a) SEM, b) Pd/MgFe2O4, c) Oxygen, d) Magnesium, e) Iron, f) Palladium.
enhanced catalytic efficiency. The effective distribution of
palladium nanoparticles and hydroxyl groups of MgFe2O4
provides an effective interaction of active catalytic species
with catalyst support and with reactant molecules. So the
catalyst efficiency in Suzuki coupling reaction was improved
and the products were obtained with excellent yield.
Catalytic activity of Pd/MgFe2O4
The catalytic activity of nano Pd/MgFe2O4 has been eval-
uated against the Suzuki coupling reaction (Scheme 1).
Reaction of Iodobenzene with phenylboronicacid was treated
as a model reaction to verify various reaction parameters.
0.50 mmol of Iodobenzene was treated with 0.75 mmol phe-
nylboronicacid in the presence of Pd/MgFe2O4 (0.2 mol% of
Pd), K2CO3 (1.00 mmol) as base in 4 ml of ethanol: water
Figure 7. Particle size distribution of Pd/MgFe2O4.
The reduced particle size of the Pd/MgFe2O4 nanocatalyst
results increased active surface area. The number of active
catalytic active sites was increased and resulting in leads to (1:1) solvent system at 80 ꢀC. Experiments were performed

6
G. K. DASARI ET AL.
Figure 8. Infrared spectrum of Pd/MgFe2O4.
Figure 9. Hysteresis curve of nanocrystalline Pd/MgFe2O4 measured at 300 K.
Figure 10. N2 adsorption-desorption isotherm of Pd/MgFe2O4 sample obtained at 77 K.

INORGANIC AND NANO-METAL CHEMISTRY
7
Scheme 1. Suzuki coupling reaction of Aryl Halides and Arylboronicacids.
Table 1. Optimization of reaction conditions for Suzuki couplinga with
Iodobenzene and Phenylboronicacid.
Solvent
Base Catalyst (mol %) Temp. (ꢀC) Time (h) Yieldb (%)
DMF
Ethanol
Water
Toluene
Ethanol/Water K2CO3
Ethanol/Water TEA
Ethanol/Water KOAc
Ethanol/Water Na2CO3
Ethanol/Water Cs2CO3
Ethanol/Water K2CO3
Ethanol/Water K2CO3
Ethanol/Water K2CO3
Ethanol/Water K2CO3
Ethanol/Water K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.5
0.1
0.2
0.2
–
80
80
80
100
80
80
80
80
80
80
80
4
12
20
8
2
2
8
2
4
1
84
86
64
69
99
92
88
94
93
96
94
58
Figure 11. Magnetic separation of Pd/MgFe2O4 from the reaction mixture.
In economical and environmental point of view, the
recovery and reuse of catalyst are most important. The cata-
lytic activity and magnetic separation of nano Pd/MgFe2O4
were investigated at present reaction conditions. The mag-
8
RT
30
15
24
50
80
86
No reaction
aReaction
conditions:
0.5 mmol
of
Iodobenzene,
0.75 mmol
of
Phenylboronicacid and 1.0 mmol of base, nano Pd/MgFe2O4 catalyst, ethanol netic property of Pd/MgFe2O4 provides an efficient magnetic
2 ml and water 2 ml, Temperature RT-80 ꢀC.
separation from the reaction mixture as shown in Figure 11.
The recyclability of Pd/MgFe2O4 catalyst for coupling reac-
bisolated yield by column chromatography
tion of Iodobenzene with Phenylboronicacid is shown in
Table 2. Suzuki cross coupling reactionsa of Aryl halides and Aryl boronic
Figure 12. After completion of the reaction, the reaction
mixture was cooled to ambient temperature and the catalyst
was separated by an external magnet. The recovered catalyst
was washed with excess EtOH, dried in vacuum oven at
100 ꢀC and reused for next cycle. The catalyst reusability
was tested up to five cycles without significant loss of its
activity. The isolated yields were decreased slightly after the
fifth cycle due to Pd leaching, which was confirmed by ICP-
AES analysis. After five cycles, the leaching of Pd was 0.1%
wt was observed.
acids by using Pd/MgFe2O4.
Aryl halide (R1)
Aryl boronic acid (R2)
X
Time (h)
Yield (%)b
H
H
H
H
H
H
I
Br
Cl
I
I
I
I
I
I
I
I
I
I
Br
I
I
I
2
4
24
1.5
2
3.5
2.5
3
2
1.5
2
2
99
96
81
93
91
93
96
94
95
97
98
94
96
92
87
96
98
3-NO2
3-NO2
4-Cl
4-COMe
4-OMe
3-NO2
4-NO2
H
4-OMe
Thienyl
Thienyl
4-OMe
Thienyl
Naphthyl
4-Me
3-NO2
4-OMe
4-OMe
4-COMe
4-Et
4-OMe
4-OMe
H
4-Me
4-Me
Thienyl
4-OMe
4-OMe
Reusability of Pd/MgFe2O4 catalyst
6
9
7
5
The heterogeneous nature of the catalyst was examined by
hot filtration test. The supported catalyst was filtered off
after 30 min of the reaction time and the filtrate was allowed
to react further for the required time under the same reac-
tion conditions. The results indicate that after this hot filtra-
tion, further reaction did not proceed. The catalyst was
heterogeneous, there is no leaching of Pd during the reac-
tion. The results were supported by ICP-AES analysis. The
leaching of Pd was not observed up to 5 cycles. Further,
after five cycles the catalyst was analyzed by SEM image
shown in Figure 10 (Supplementary information). It clearly
showed that the catalyst was highly stable and reusable.
4
aReaction conditions: 0.5 mmol of Aryl Halide, 0.75 mmol of Aryl boronic acid
and 1.0 mmol of K2CO3, 0.2 mol% nano Pd/MgFe2O4 catalyst, ethanol 2 ml
and water 2 ml, 80 ꢀC.
bIsolated yield by column chromatography
to optimize the reaction parameters such as catalyst loading,
solvent, base and temperature.
The investigated experimental results explored the opti-
mized reaction conditions were found in Ethanol: Water
solvent media with 0.2 mol% of Pd (Pd/MgFe2O4) at 80 ꢀC
temperature in the presence of K2CO3 as a base for about
2 h (Table 1).
The scope of the reaction was studied with various sub-
stituents (electron withdrawing and electron releasing
nature) on both Aryl halides and Arylboronicacids (Table
2). The obtained yields are good to excellent with various
Aryl, Heteroaryl Halides and Boronicacids depending on the
nature of substituent due to electronic effects.
Comparison of catalytic activity for Suzuki
coupling reaction
The catalytic activity of Pd/MgFe2O4 in the preparation of
biphenyl using Iodobenzene and Phenylboronicacid was
compared with various palladium nanocatalysts reported in
literature. The Pd/MgFe2O4 nanocatalyst showed remarkable

8
G. K. DASARI ET AL.
Figure 12. Recyclability of Pd/MgFe2O4 with Iodobenzene and Phenylboronicacid cross coupling reaction.
Table 3. Comparison of various MgFe2O4 catalyst preparation methods.
Catalyst
Preparation method
Application
Ref.
Pd/MgFe2O4
One-step synthesis
Suzuki coupling
Present work
1. Pd/MgFe2O4 synthesis by Co-precipitation,
Two-step synthesis 1. MgFe2O4 synthesis by Sol-gel, 2. Colloidal deposition of
synthesized Au nanoparticles
Au/ MgFe2O4
Pt/MgFe2O4
CO-oxidation
CO-oxidation
[15(a)]
[15(b)]
Two-step synthesis
1. MgFe2O4 synthesis by solid-state method,
2. Colloidal deposition of synthesized Pt nanoparticles.
Three-step synthesis
1. MgFe2O4 synthesis by Co-precipitation,
2. MgO/MgFe2O4 synthesis by impregnation,
3. Colloidal deposition of synthesized Au nanoparticles.
Au /MgO/MgFe2O4
Benzyl alcohols
oxidation
[15(c)]
activity with 99% yield with 0.2 mol% palladium loadings reported methods, requires minimum number of operations
(TON-495, TOF-247.5 hꢂ1) toward ligand less Suzuki cou-
and minimal instrumentation.
pling reaction utilizing greener solvent mixture Water:
Ethanol. Moreover, the catalyst preparation procedure is
Application of Pd/MgFe2O4 nanocatalyst in synthesis of
one-step co-precipitation, salt cage assisted calcination. Pd/
PCI-32765
MgFe2O4 was one of the efficient catalysts among the
reported un-functionalized and functionalized catalysts.
The prepared Pd/MgFe2O4 nanocatalyst was applied for the
synthesis of 5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimi-
din-4-ylamine an intermediate in preparation of the mar-
R
V
keted drug PCI-32765 under the name IMBRUVICA
Comparison of catalyst preparation methods
(Ibrutinib -BTK inhibitor). Our group successfully prepared
the drug PCI-32765 by a new synthetic approach.[25] The
The proposed catalyst preparation was compared with
reported methods; magnesium ferrite supported metal cata-
lysts and shown in Table 3. Generally, multi-step synthesis
and numerous operations were involved in the preparation
of catalysts. The present work is a one-step coprecipitation
and in-situ formed by-products act as a masking agent dur-
ing calcination. This methodology is superior, does not
involves additives, templating agent and surface modifiers.
molecule is biologically active and can be used as an anti-
cancer drug to treat B cell cancers like mantle cell lymph-
€
oma, chronic lymphocytic leukemia, and Waldenstrom’s
macroglobulinemia, a form of non-Hodgkin’s lymphoma by
binding the Bruton’s tyrosine kinase(BTK) protein of B cells.
The synthetic intermediate 5-(4-phenoxyphenyl)-7H-pyr-
rolo[2,3-d]pyriMidin-4-ylamine can be easily prepared from
Proposed method is more efficient compared to other commercially available 3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-

INORGANIC AND NANO-METAL CHEMISTRY
9
Scheme 2. Synthesis of PCI-32765.
4-amine and 4-phenoxybenzeneboronicacid by Suzuki cou- d]pyrimidin-4-ylamine, an important intermediate for pre-
pling reaction (Scheme 2). The active molecule PCI-32765 paring the marketed drug PCI-32765.
can be synthesized by reacting obtained product with 1-
(tert-butoxycarbonyl) piperidin-3-yl methanesulfonate,[26]
simultaneous deprotection and amide formation with
Acknowledgments
The authors are very thankful to SAIF Department IIT Bombay, India,
Center for Excellence: Nanotechnology, Andhra University,
Visakhapatnam, India. The authors are thankful to M/S Shilpa
Medicare Limited for providing the opportunity and Dr. Sriram
Rampalli, Dr. Lavkumar Upalla for continuous support and
encouragement.
Acrylic acid. The magnetically recoverable Pd/MgFe2O4 is
an efficient catalyst in the synthesis of intermediate for pre-
paring PCI-32765 drug and, the obtained product was hav-
ing negligible content of trace metals <2ppm.
Conclusions
References
In conclusion, we have prepared a new, palladium nanopar-
ticles loaded magnesium ferrite nanocatalyst (Pd/MgFe2O4)
was synthesized by one-step co-precipitation using ultra-
sound; in-situ formed by-products assisted salt cage calcin-
ation method. The catalyst was well characterized by using
SEM-EDS, TEM, FT-IR, XPS, XRD, VSM, BET, and ICP-
AES. The synthesized Pd/MgFe2O4 was magnetically separ-
able (Saturation magnetization Ms ¼ 19.85 emu/g), having
particle size (TEM) 5 nm to 18 nm and posses specific sur-
1. (a) Chng, L. L.; Erathodiyil, N.; Ying, J. Y. Nanostructured
Catalysts for Organic Transformations. Acc. Chem. Res. 2013, 46,
1825. (b) Sharma, N.; Ojha, H.; Bharadwaj, A.; Pathak, D. P.;
Sharma, R. K. Preparation and Catalytic Applications of
Nanomaterials: A Review. RSC Adv. 2015, 5, 53381. DOI: 10.
1039/C5RA06778B.
2. (a) Sharma, R. K.; Dutta, S.; Sharma, S.; Zboril, R.; Varma, R. S.;
Gawande, M. B. Fe3O4 (Iron Oxide)-Supported Nanocatalysts:
Synthesis, Characterization and Applications in Coupling
Reactions. Green Chem. 2016, 18, 3184. (b) Karimi, B.;
Mansouri, F.; Mirzaei, H. M. Recent Applications of
Magnetically Recoverable Nanocatalysts in C-C and C-X
Coupling Reactions. ChemCatChem. 2015, 7, 1736. DOI: 10.
1002/cctc.201403057.
3. (a) Fodor, A.; Hell, Z.; Pirault-Roy, L.; The Influence of the
Nature of the Support on the Copper–Palladium Catalysed
Suzuki–Miyaura-Coupling. Catal. Lett. 2016, 146, 596. (b) Yang,
J.; Tian, C.; Wang, L.; Fu, H. An Effective Strategy for Small-
Sized and Highly-Dispersed Palladium Nanoparticles Supported
on Graphene with Excellent Performance for Formic Acid
Oxidation. J. Mater. Chem. 2011, 21, 3384. DOI: 10.1039/
c0jm03361h.
face area 31.28 m2
g
ꢂ1. The active phase palladium was
effectively dispersed and Pd/MgFe2O4 particle size was con-
trolled by minimizing aggregation risk during calcination.
The palladium nanoparticles preparation was carried out
without using additional reducing agents such as Hydrazine,
Sodium borohydride, Hydrogen. This one-step preparation
method was simple, efficient and having very less number of
process operations, can be used for several potential nanoca-
talysts. The catalyst preparation process was useful for pre-
paring several potential nano catalytic systems having
numerous industrial applications. The active catalyst effica-
ciously catalyzed the Suzuki coupling reaction without using
toxic Phosphine ligands. The Pd/MgFe2O4 catalyst is
reusable up to 5 cycles with superior catalytic activity. The
magnetic nature of the catalyst provides the ease of separ-
ation from the reaction mixture in the presence of an
applied external magnetic field, which eliminates the need of
catalyst filtration after completion of the reaction.
Furthermore, easy isolation of the crude products, negligible
metal contamination and reusability of the catalyst can have
a huge green impact and industrial interest. The proposed
nano Pd/MgFe2O4 catalyst was successfully applied in the
4. Kharisov, B. I.; Rasika Dias, H. V.; Kharissova, O. V. Mini-
Review: Ferrite Nanoparticles in the Catalysis. Arab. J. Chem.
2019, 12, 1234–1246. DOI: 10.1016/j.arabjc.2014.10.049.
5. (a) He, J.; Yang, S.; Riisager, A. Magnetic Nickel Ferrite
Nanoparticles as Highly Durable Catalysts for Catalytic Transfer
Hydrogenation of Bio-Based Aldehydes. Catal. Sci. Technol.
2018, 8, 790–797. (b) Mapossa, A. B.; Dantas, J.; Silva, M. R.;
Kiminami, R. H. G. A.; Costa, A. C. F. M.; Daramola, M. O.
Catalytic Performance of NiFe2O4 and Ni0.3Zn0.7Fe2O4 Magnetic
Nanoparticles During Biodiesel Production. Arab. J. Chem. 2019,
in press. (c) Kalam, A.; Al-Sehemi, A. G.; Assiri, M.; Du, G.;
Ahmad, T.; Ahmad, I.; Pannipara, M. Modified Solvothermal
Synthesis of Cobalt Ferrite (CoFe2O4) Magnetic Nanoparticles
Photocatalysts for Degradation of Methylene Blue with H2O2/
Visible Light. Results Phys. 2018, 8, 1046–1053. (d) Han, F.; Xu,
synthesis
of
5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-

10
G. K. DASARI ET AL.
X.; Fu, Y.; Wang, X. Synthesis of Rice-Husk-Carbon-Supported
Nickel Ferrite Catalyst for Reduction of Nitrophenols. J. Nanosci.
Nanotechnol. 2019, 19, 5838–5846. (e) Ibrahim, I.; Athanasekou,
C.; Manolis, G.; Kaltzoglou, A.; Nasikas, N. K.; Katsaros, F.;
Devlin, E.; Kontos, A. G.; Falaras, P. Photocatalysis as an
Advanced Reduction Process (ARP): The Reduction of 4-
Nitrophenol Using Titania Nanotubes-Ferrite Nanocomposites. J.
Hazard. Mater. 2019, 372, 37–44. (f) Moslehi, A.; Zarei, M.
Application of Magnetic Fe3O4 Nanoparticles as a Reusable
Heterogeneous Catalyst in the Synthesis of b-Lactams
Containing Amino Groups. New J. Chem. 2019, 43,
12690–12697. DOI: 10.1039/C9NJ02759A.
Ghomi, J.; Akbarzadeh, Z. Ultrasonic Accelerated Knoevenagel
Condensation by Magnetically Recoverable MgFe2O4
Nanocatalyst: A Rapid and Green Synthesis of Coumarins Under
Solvent-Free Conditions. Ultrason. Sonochem. 2018, 40, 78–83.
(g) Patil, J. Y.; Nadargi, D. Y.; Mulla, I. S.; Suryavanshi, S. S.
Cerium Doped MgFe2O4 Nanocomposites: Highly Sensitive and
Fast Response-Recoverable Acetone Gas Sensor. Heliyon. 2019,
5, e01489. (h) Baby, J. N.; Sriram, B.; Wang, S.-F.; George, M.
Effect of Various Deep Eutectic Solvents on the Sustainable
Synthesis of MgFe2O4 Nanoparticles for Simultaneous
Electrochemical Determination of Nitrofurantoin and 4-
Nitrophenol. ACS Sustain. Chem. Eng. 2020, 8, 1479–1486. DOI:
10.1021/acssuschemeng.9b05755.
6. Saire-Saire, S.; Barbosa, E. C. M.; Garcia, D.; Andrade, L. H.;
Garcia-Segura, S.; Camargo, P. H. C.; Alarcon, H. Green 15. (a) Jia, C.-J.; Liu, Y.; Schwickardi, M.; Weidenthaler, C.;
Synthesis of Au Decorated CoFe2O4 Nanoparticles for Catalytic
Reduction of 4-Nitrophenol and Dimethylphenylsilane
Oxidation. RSC Adv. 2019, 9, 22116–22123. DOI: 10.1039/
C9RA04222A.
Spliethoff, B.; Schmidt, W.; Sch
u€th, F. Small Gold Particles
Supported on MgFe2O4 Nanocrystals as Novel Catalyst for CO
Oxidation. Appl. Catal. A. 2010, 386, 94. (b) Zheng, B.; Wu, S.;
Yang, X.; Jia, M.; Zhang, W.; Liu, G. Room Temperature CO
Oxidation over Pt/MgFe2O4: A Stable Inverse Spinel Oxide
Support for Preparing Highly Efficient Pt Catalyst. ACS Appl.
Mater. Interfaces 2016, 8, 26683. (c) Moura de, E. M.; Garcia,
M. A. S.; Gonc¸alves, R. V.; Kiyohara, P. K.; Jardim, R. F.; Rossi,
L. M. Gold Nanoparticles Supported on Magnesium Ferrite and
Magnesium Oxide for the Selective Oxidation of Benzyl Alcohol.
RSC Adv. 2015, 5, 15035. (d) Hassanzadeh, S.; Eisavi, R.;
Abbasian, M. Preparation and Characterization of Magnetically
Separable MgFe2O4/Mg(OH)2 Nanocomposite as an Efficient
Heterogeneous Catalyst for Regioselective One-Pot Synthesis of
b-Chloroacetates from Epoxides. Appl. Organometal. Chem.
2018, 32:e4520. (e) Rahmanivahid, B.; Pinilla-de Dios, M.;
Haghighi, M.; Luque, R. Mechanochemical Synthesis of CuO/
MgAl2O4 and MgFe2O4 Spinels for Vanillin Production from
Isoeugenol and Vanillyl Alcohol. Molecules. 2019, 24, 2597. (f)
Ramos-Ramꢀırez, E.; Tzompantzi-Morales, F.; Gutiꢀerrez-Ortega,
N.; Mojica-Calvillo, H.G.; Castillo-Rodrꢀıguez, J. Photocatalytic
Degradation of 2,4,6-Trichlorophenol by MgO–MgFe2O4
Derived from Layered Double Hydroxide Structures. Catalysts.
2019, 9, 454. (g) Godlyn Abraham A.; Manikandan A.;
Manikandan E.; Vadivel S.; Jaganathan S. K.; Baykal A.; Sri
Renganathan P. Enhanced Magneto-Optical and Photo-Catalytic
Properties of Transition Metal Cobalt (Co2þ Ions) Doped Spinel
MgFe2O4 Ferrite Nanocomposites. J. Magnet. Magnet. Mater.
2018, 452, 380–388. (h) Kamzin, A. S.; Das, H.; Wakiya, N.
Magnetic Core/Shell Nanocomposites MgFe2O4/SiO2 for
Biomedical Application: Synthesis and Properties. Phys. Solid
State. 2018, 60, 1752–1761. DOI: 10.1134/S1063783418090147.
16. (a) Torborg, C.; Beller, M.; Recent Applications of Palladium-
Catalyzed Coupling Reactions in the Pharmaceutical,
Agrochemical, and Fine Chemical Industries. Adv. Synth. Catal.
2009, 351, 3027–3043. (b) Devendar, P.; Qu, R.-Y.; Kang, W.-M.;
He, B.; Yang, G.-F. Palladium-Catalyzed Cross-Coupling
Reactions: A Powerful Tool for the Synthesis of Agrochemicals.
J. Agric. Food Chem. 2018, 66, 8914–8934. DOI: 10.1021/acs.jafc.
8b03792.
7. Dutta, M. M.; Talukdar, H.; Phukan, P. CuI Incorporated Cobalt
Ferrite Nanoparticles as a Magnetically Separable Catalyst for
Oxidative Amidation Reaction. Dalton Trans. 2019, 48,
16041–16052. DOI: 10.1039/C9DT03440D.
8. (a) Hajalilou, A.; Mazlan, S. A. A review on preparation techni-
ques for synthesis of nanocrystalline soft magnetic ferrites and
investigation on the effects of microstructure features on mag-
netic properties. Appl. Phys. A 2016, 122, 680. (b) Ortiz-
~
Quinonez, J.-L.; Pal, U.; Villanueva, M. S. Structural, Magnetic,
and Catalytic Evaluation of Spinel Co, Ni, and Co–Ni Ferrite
Nanoparticles Fabricated by Low-Temperature Solution
Combustion Process. ACS Omega. 2018, 3, 14986–15001 DOI:
10.1021/acsomega.8b02229.
9. Fino, D.; Russo, N.; Saracco, G.; Specchia, V. CNG Engines
Exhaust Gas Treatment via Pd-Spinel-Type-Oxide Catalysts.
Catal. Today 2006, 17, 559. DOI: 10.1016/j.cattod.2006.06.003.
10. Rashad, M. M. Magnetic Properties of Nanocrystalline
Magnesium Ferrite by Co-Precipitation Assisted with Ultrasound
Irradiation. J. Mater. Sci. 2007, 42, 5248–5255. DOI: 10.1007/
s10853-006-0389-9.
11. Senapati, K. K.; Roy, S.; Borgohain, C.; Phukan, P. Palladium
Nanoparticle Supported on Cobalt Ferrite: An Efficient
Magnetically Separable Catalyst for Ligand Free Suzuki
Coupling. J. Mol. Catal. A Chem. 2012, 352, 128–134. DOI: 10.
1016/j.molcata.2011.10.022.
12. Govha, J.; Bala Narasaiah, T.; Kumar, P.; Shilpa Chakra, C.
Synthesis of Nano-Magnesium Ferrite Spinel and Its
Characterization. Int. J. Eng. Res. Technol. (IJERT). 2014, 3,
1420.
13. Maensiri, S.; Sangmanee, M.; Wiengmoon, A. Magnesium Ferrite
(MgFe2O4) Nanostructures Fabricated by Electrospinning.
Nanoscale Res. Lett. 2009, 4, 221–228.
14. (a) Bououdina, M.; Al-Najar, B.; Falamarzi, L.; Judith Vijaya, J.;
Shaikh, M. N.; Bellucci, S.; Effect of Annealing on Phase
Formation, Microstructure and Magnetic Properties of MgFe2O4
Nanoparticles for Hyperthermia. Eur. Phys. J. Plus. 2019, 134,
84. (b) Erdawati, E.; Darsef, D, Synthesis of Magnesium Ferrites
for the Adsorption of Congo Red from Aqueous Solution Using
Batch Studies. IOP Conf. Ser. Mater. Sci. Eng. 2018, 335, 012024.
(c) Arun Kumar, N. S.; Ashoka, S.; Pandurangappa, M. MgFe2O4
Nanoparticles Synthesis and Characterization: Application to
17. Zhang, F.; Niu, J.; Wang, H.; Yang, H.; Jin, J.; Liu, N.; Zhang, Y.;
Li, R.; Ma, J. Palladium Was Supported on Super Paramagnetic
Nanoparticles: A Magnetically Recoverable Catalyst for Heck
Reaction. Mater. Res. Bull. 2012, 47, 2, 504–507. DOI: 10.1016/j.
materresbull.2011.10.030.
Trace Level Mercury(II) Measurement from Waste Water 18. Rathi, A. K.; Gawande, M. B.; Pechousek, J.; Tucek, J.; Aparicio,
Samples. Mater. Res. Express. 2019, 6, 125049. (d) Abdellah, W.;
C.; Petr, M.; Tomanec, O.; Krikavova, R.; Travnicek, Z.; Varma,
R. S.; Zboril, R. Maghemite Decorated with Ultra-Small
Palladium Nanoparticles (c-Fe2O3–Pd): Applications in the
Heck–Mizorokiolefination, Suzuki Reaction and Allylic
Oxidation of Alkenes. Green Chem. 2016, 18, 2363. DOI: 10.
1039/C5GC02264A.
-
Ezzat, A; Samir, I. Removal of Pertechnetate (99TcO4 ) from
Liquid Waste by Magnesium Ferrite (MgFe2O4) Nanoparticles
Synthesized Using Sol-Gel Auto Combustion Method. Open J.
Appl. Sci. 2019, 9, 68–86. (e) Ali, N. A.; Idris, N. H.; Din,
M. F. M.; Mustafa, N. S.; Sazelee, N. A.; Halim Yap, F. A.;
Sulaiman, N. N.; Yahya, M. S.; Ismail, M. Nanolayer-Like- 19. Jadhav, V. G.; Bhojane, J. M.; Nagarkar, J. M. Palladium on
Shaped MgFe2O4 Synthesised via
Method and Its Catalytic Effect on the Hydrogen Storage
Properties of MgH2. RSC Adv. 2018, 8, 15667–15674. (f) Safaei
a
Simple Hydrothermal
Manganese Ferrite: An Efficient Catalyst for One Pot Synthesis
of Primary Amides from Iodobenzene. RSC Adv. 2015, 5,
6636–6641. DOI: 10.1039/C4RA12827C.

INORGANIC AND NANO-METAL CHEMISTRY
11
20. (a) Dehghani Firuzabadi F.; Asadi Z.; Panahi F.; Immobilized
NNN Pd-Complex on Magnetic Nanoparticles: Efficient and
Reusable Catalyst for Heck and Sonogashira Coupling Reactions
RSC Adv. 2016, 6, 101061. (b) Wang, J.; Xu, B.; Sun, H.; Song,
G. Palladium Nanoparticles Supported on Functional Ionic
Liquid Modified Magnetic Nanoparticles as Recyclable Catalyst
for Room Temperature Suzuki Reaction. Tet. Lett. 2013, 54, 238.
(c) Singh, A. S.; Shelkar, R. S,; Nagarkar, J. M. Palladium(II) on
Functionalized NiFe2O4: An Efficient and Recyclable Phosphine-
Free Heterogeneous Catalyst for Suzuki Coupling Reaction.
Catal. Lett. 2015, 145, 723. (d) Ghorbani-Vaghei, R.; Hemmati,
S.; Hekmati, M. Pd Immobilized on Modified Magnetic Fe3O4
Nano-Particles: Magnetically Recoverable and Reusable Pd
Nanocatalyst for Suzuki-Miyaura Coupling Reactions and
Ullmann-Type N-Arylation of Indoles J. Chem. Sci. 2016, 128,
1157. (e) Mahmoudzadeh, M.; Mehdipour, E.; Eisavi, R.
MgFe2O4@SiO2-PrNH2/Pd/bimenthonoxime Core-Shell Magnetic
Nanoparticles as a Recyclable Green Catalyst for Hete-rogeneous
Suzuki Cross-Coupling in Aqueous Ethanol. J. Coord. Chem.
2019, 72, 841.
and High Saturation Magnetization. RSC Adv. 2013, 3, 13961.
DOI: 10.1039/c3ra41543k.
22. CH Q3D (R1) Guideline for Elemental Impurities, ICH
International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use (ICH).
Official web sitehttps://database.ich.org/sites/default/files/Q3D-
R1EWG_Document_Step4_Guideline_2019_0322.pdf
(accessed
Jan 10, 2020).
23. Todd, B.; Darren, D.; Joshua, C. H.; Shuang, L.; Renee, M. Z.
Heteroaromatic Compounds as btk Inhibitors. 2014, PCT Int.
Appl. WO/2014/152114A1.
24. Fariba, S.; Ali, R.; Hamideh, A.; Saeid, T. F.; Pegah, A. A.;
Mehdi, K.; Sang, W. J.; Nahid, D. Aqueous-Phase Oxidation of
Alcohols with Green Oxidants (Oxone and Hydrogen Peroxide)
in the Presence of MgFe2O4 Magnetic Nanoparticles as an
Efficient and Reusable Catalyst. J. Nanostruct. 2016, 6, 264.
25. Rampalli, S.; Upalla, L. K.; Patneedi, C. B.; Dasari, G. K.;
Chaturvedi, A. K. Process for the Preparation of Ibrutinib. 2017,
PCT Int. Appl., WO/2017/134588.
26. Muddasani, P.; Budideti, S. R.; Madalapu, V.; Gattu, A.; Konda,
B. A.; Nannapaneni, V. C. A Process for the Preparation of
Ibrutinib. 2017, PCT Int. Appl. WO/2017/134684.
21. Wenshu, T.; Su, Y.; Li, Q.; Shian Gand Jian, K. S. Well-
Dispersed, Ultrasmall, Superparamagnetic Magnesium Ferrite
Nanocrystallites with Controlled Hydrophilicity/Hydrophobicity