Efficient Reduction of C–N Multiple Bonds Catalyzed by Magnetically Retrievable Magnetite Nanoparticles with Sodium Borohydride

Article abstract of DOI:10.1007/s10562-016-1822-6

Abstract: A simple, rapid and efficient methodology has been developed for the reductive transformation of the compounds bearing C–N multiple bonds such as oximes and nitriles to the corresponding amines by sodium borohydride catalyzed by highly active solid Fe₃O₄ nanoparticles. The catalyst was easily recovered using external magnet and reused five times without losing its catalytic activity. Graphical Abstract: A simple, rapid, efficient and reusable heterogeneous catalytic system has been developed for the reductive transformation of oximes and nitriles into corresponding amines by sodium borohydride in presence of Fe₃O₄ nanoparticles.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10562-016-1822-6

Catal Lett
DOI 10.1007/s10562-016-1822-6
Efficient Reduction of C–N Multiple Bonds Catalyzed
by Magnetically Retrievable Magnetite Nanoparticles
with Sodium Borohydride
Pratibha Kumari1 Renu Gautam1 Harshit Yadav1 Vikas Kushwaha1
•
•
•
•
Avinash Mishra1 Shilpi Gupta1 Veena Arora1
•
•
Received: 26 May 2016 / Accepted: 16 July 2016
Ó Springer Science+Business Media New York 2016
Abstract A simple, rapid and efficient methodology has
been developed for the reductive transformation of the
compounds bearing C–N multiple bonds such as oximes
and nitriles to the corresponding amines by sodium boro-
hydride catalyzed by highly active solid Fe3O4 nanoparti-
cles. The catalyst was easily recovered using external
magnet and reused five times without losing its catalytic
activity.
Keywords Heterogeneous catalysis Á Nanotechnology Á
Magnetic separation Á Reduction Á Nanoparticles Á
Recycling
1 Introduction
The reductive transformation of compounds bearing C–N
multiple bonds to amines is one of the most versatile syn-
thetic routes to synthesize various functionalized amines.
Amine compounds represent a versatile class of biologically
active molecules that includes various types of alkaloids,
neurotransmitters, amino acids and pharmaceutical agents.
Amines are crucial precursors for the biosynthesis of diverse
biomolecules as well [1]. Various amino compounds have
also been used to manufacture different types of dyes,
antioxidants, photographic materials, agriculture chemicals
and corrosion inhibitors. Recently, synthetic strategies for
the reduction of oximes and nitriles into amines have
received much attention in research and development pro-
gramme at both academic and industrial level.
Graphical Abstract A simple, rapid, efficient and reu-
sable heterogeneous catalytic system has been developed
for the reductive transformation of oximes and nitriles into
corresponding amines by sodium borohydride in presence
of Fe3O4 nanoparticles.
NOH
NH2
NaBH Fe O NPs
R
R
,
4
R
R
R'
3
4
R'
CH2NH2
MeOH
CN
Sodium borohydride (NaBH4) is one of the most widely
used mild and selective hydride transferring agents in
organic synthesis [2]. Sodium borohydride does not nor-
mally reduce groups like ester, nitro, amides and nitriles.
The reduction capacities of sodium borohydride can be
modified by some additives, in particular, transition metals.
There are a few reports known for the reductive conversion
of oximes and nitriles into amines using NaBH4 in com-
bination with some additives such as NaBH4/ZrCl4 [3],
NaBH4/TiCl4 [4, 5] NaBH4/CuSO4 [6], NaBH4 in acidic
[7–9] or basic condition [10], NaBH4/NiCl2 [11], NaBH4/
InCl3 [12] and NaBH4/Nickel [13]. These methods suffer
from some disadvantages such as harsh reaction conditions
A part of the manuscript has been presented in ‘‘International
Conference on Material Science & Technology’’ organized by
Department of Chemistry, University of Delhi, New Delhi (March
1–4, 2016).
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-016-1822-6) contains supplementary
material, which is available to authorized users.
& Pratibha Kumari
pratibhatanwar77@gmail.com
1
Department of Chemistry, Deshbandhu College, University
of Delhi, Kalkaji, New Delhi 110019, India
123

P. Kumari et al.
2.2 Synthesis of Fe3O4 Nanoparticles
(strong acidic or basic reaction media), limitation to use
acid or base sensitive functional groups, prolonged reaction
time, high temperature, tedious isolation process, decom-
position of the catalyst, formation of side products and low
reducing capability which produces hydroxylamine.
Therefore, there is an immense interest to develop an
efficient, rapid, simple and reusable reductive system for
the selective conversion of oximes and nitriles into corre-
sponding amines.
Nanoparticles of Fe3O4 were prepared by chemical
coprecipitation method [22]. To a solution of FeCl3Á6H2O
(2.35 g) and FeCl2Á4H2O (0.86 g) in distilled water
(40 mL), aqueous ammonia solution (25 %, 40 mL) was
added drop wise under nitrogen atmosphere with vigorous
stirring over a period of 20 min. The solution was heated to
70 °C for 5 h, and Fe3O4 nanoparticles were separated
from the resulting black dispersion by external magnet and
washed three times with water and ethanol. The final
product was dried under vacuum.
Nanoparticles have been used as highly active, mild and
selective catalysts in several organic transformations as
they are exposed to more reactant molecules due to their
large surface area [14]. Magnetic Fe3O4 (magnetite)
nanoparticles have attracted a great attention as heteroge-
neous catalyst due to its simple handling, easy recovery
with an external magnetic field, high stability and high
catalytic activities in various organic transformations [15].
Recently, Magnetic Fe3O4 nanoparticles have been used as
catalyst for efficient reduction of nitro compound [16] and
organic azide compounds into corresponding amino com-
pounds [17]. In continuation of our research pertaining to
the use of sodium borohydride as a reducing agent for
selective reductions of flavonoids [18], isoflavonoids [19]
and atrazine [20], herein, we report reductive conversion of
various oximes and nitriles to corresponding amines with
sodium borohydride catalyzed by Fe3O4 nanoparticles
under different reaction conditions.
2.3 General Procedure for the Reduction of Oximes
and Nitriles with Sodium Borohydride
Catalyzed by Fe3O4 Nanoparticles
To the solution of substrate (10 mmol) in dry methanol
(25 mL), Fe3O4 nanoparticles (50 mg) were added and the
solution was sonicated for 10 min and then vigorously
stirred at 40 °C. Sodium borohydride (30 mmol) was
added in small lots cautiously while stirring the solution for
30 min and the progress of the reaction was monitored by
thin layer chromatography (TLC). After the completion of
reaction, the catalyst was separated by using external
magnet and the reaction mixture was diluted with water
and extracted with ethyl acetate. The organic layer was
washed with brine solution and then separated and dried
over anhydrous sodium sulfate. The solvent was evapo-
rated under reduced pressure and the crude product was
purified by column chromatography over silica gel
(100–200 mesh) using ethyl acetate-hexane mixture
(varying concentration) as the eluent. All products were
analyzed by IR and NMR spectra which were in good
agreement with the reported values [5, 10].
2 Experimental
2.1 Methods and Materials
Powder X-ray diffraction data were carried out using a
Bruker D8 Advance diffractometer using Ni-filtered CuKa
radiation. Transmission electron microscopy (TEM) stud-
ies were carried out using a FEI Netherlands, Technai
G2T30, U-Twin TEM instrument operated at 200 kV. The
dispersed sample of Fe3O4 nanoparticles prepared by
treating nanoparticles in ethanol with ultrasound sonicator
and then a few drops were put on a copper grid and dried in
air. Scanning Electron Microscopy studies were carried out
using JEOL, JSM 6610LV SEM instrument. 1H NMR
spectra were recorded using a Jeol, JNM-EXCP 400 NMR
spectrometer at 400 MHz. FT-IR spectra were recorded
using Perkin Elmer, Spectrum RXI—Mid IR. Thin layer
chromatography (TLC) was done over silica gel 60 F254
aluminum sheet. All solvents and reagents were purchased
from commercial sources with the best quality and they
were used without further purification. All oximes were
prepared by the reaction of corresponding aldehydes and
ketones with hydroxylamine hydrochloride under different
conditions [21].
1
Benzylamine H NMR (CDCl3, 400 MHz): d 7.29–7.33
(m, 5H, ArH), 3.86 (s, 2H, CH2), 1.49 (br s, 2H, NH2); IR
(film): 3367, 3296, 3062, 3027, 2919, 2850, 1586, 1495,
1453, 737, 698 cm-1
.
Cyclohexylamine 1H NMR (CDCl3, 400 MHz): d
2.59–2.54 (m, 1H, NCH), 1.78–1.74 (m, 2H, CH2),
1.68–1.65 (m, 2H, CH2), 1.57–1.53 (m, 1H, CH), 1.29 (br
s, 2H, NH2), 1.27–1.16 (m, 2H, CH2), 1.11–1.03 (m, 1H,
CH), 1.00–0.94 (m, 2H, CH2); IR (film): 3349, 3249, 2927,
2853, 1586, 1449 cm-1
.
1
4-Methyl benzylamine H NMR (CDCl3, 400 MHz): d
7.22 (d, J = 8.4 Hz, 2H, ArH), 7.17 (d, J = 8.4 Hz, 2H,
ArH), 3.85 (s, 2H, CH2), 2.36 (s, 3H, CH3), 1.51 (br s, 2H,
NH2); IR (film): 3381, 3309, 2919, 1481, 1329, 794 cm-1
.
1
4-Chloro benzylamine H NMR (CDCl3, 400 MHz): d
7.28 (m, 2H, ArH), 7.22 (m, 2H, ArH), 3.82 (s, 2H, CH2),
1.48 (br s, 2H, NH2); IR (film): 3369, 2861, 1595, 1491,
1091, 815 cm-1
.
123

Efficient Reduction of C–N Multiple Bonds Catalyzed by Magnetically Retrievable Magnetite…
1
4-Bromo benzylamine H NMR (CDCl3, 400 MHz): d
7.27 (m, 2H, ArH), 7.22 (m, 2H, ArH), 3.82 (s, 2H, CH2),
1.49 (br s, 2H, NH2).
diffraction peaks are in good agreement with the XRD
standard for Fe3O4 nanoparticle (JCPDS no. 85-1436) [24].
The results indicate the spinel phase structure of magnetite
nanoparticles and support a cubic crystal system. The
morphology of the prepared magnetite nanoparticles was
1-Phenylethylamine 1H NMR (CDCl3, 400 MHz): d
7.32–7.21 (m, 5H, ArH), 4.10 (q, J = 7.2 Hz, 1H, NCH),
2.09 (br s, 2H, NH2), 1.39 (d, J = 7.2 Hz, 3H, CH3).
1
1-Propylamine H NMR (CDCl3, 400 MHz): d 2.61 (t,
J = 6.9, 2H, CH2), 1.46–1.37 (m, 4H, NH2 and CH2), 0.87
(t, J = 7.3, 3H, CH3); IR (film): 3418, 2923, 2851, 1560,
1466, 1053 cm-1
1
1-Butyl amine H NMR (CDCl3, 400 MHz): d 2.66 (t,
J = 6.8 Hz, 2H, NCH2), 1.42–1.27 (m, 6H, CH2 and NH2),
0.89 (t, J = 7.2 Hz, 3H, CH3); IR (film): 3429, 2931, 1608,
1512, 1467 cm-1
.
3 Results and Discussion
3.1 Characterization of Magnetite (Fe3O4)
Nanoparticles
Fig. 1 Powder XRD data of Fe3O4 nanoparticles
Magnetite nanoparticles were prepared by chemical co-
precipitation method under alkaline condition and were
characterized by different techniques. The FT-IR spectrum
of Fe3O4 MNPs (Supporting Information, Fig. S1) exhibits
a prominent band as around 580 cm-1 which corresponds
to stretching vibration of metal–oxygen bond (Feoctahedral
–
O–Fetetrahedral stretching vibrations) for the spinel structure
of iron oxide [23]. A broad band at 3417 cm-1 indicates
that presence of hydroxyl group on the surface of Fe3O4
nanoparticles. The phase and crystalline structures of
Fe3O4 nanoparticles were determined by powder X-ray
diffraction (P-XRD) (Fig. 1). It was found that the P-XRD
pattern of Fe3O4 exhibits diffraction lines (hkl) corre-
sponding to the crystal planes at (200) (311), (400), (422),
(511) and (440). The position and relative intensity of
Fig. 2 SEM image of Fe3O4 nanoparticles
Fig. 3 TEM image of Fe3O4 nanoparticles (left), selected electron area diffraction pattern (SEAD) (right)
123

P. Kumari et al.
studied by scanning electron microscopy (SEM) technique
(Fig. 2). The shape, size, and morphology of the Fe3O4
nanoparticles were also analyzed by using transmission
electron microscopy (TEM) technique. It is observed from
Fig. 3 that the magnetite nanoparticles are cubic in shape
and their sizes are almost uniform. The SEAD pattern
shows the reflections at (200), (311), (400), (422), (511)
and (440) hkl positions (Fig. 3) which are also present in
P-XRD pattern. The size distribution of nanoparticles is
shown in Fig. 4. Energy-dispersive X-ray spectrometry
data (EDX) (Supporting Information, Fig. S2) confirms the
presence of iron and oxygen and thus the formation of
Fe3O4 nanoparticles without any impurity peak. The
presence of carbon and copper is due to the usage of carbon
coated copper grid for sample preparation. The thermo-
gravimetric analysis (TGA) (Supporting Information,
Fig. S3) of Fe3O4 nanoparticles indicates decomposition at
100–290 °C which may be attributed to the removal of
absorbed water molecules.
3.2 Catalytic Activity of Fe3O4 Nanoparticles
The reductions of compounds containing C–N multiple
bonds such as oximes and nitriles have been studied with
sodium borohydride catalyzed by magnetite nanoparticles
in methanol. To optimize the reaction conditions, ben-
zaldehyde oxime was used as a model substrate (Table 1).
The reduction of benzaldehyde oxime with sodium boro-
hydride in absence of catalyst gives corresponding amine
in poor yield. However, the presence of magnetite
nanoparticles in this reduction reaction improves the yield
of primary amine significantly (Table 1). It was observed
that the yield increased considerably when the amount of
sodium borohydride was increased from 1 mol equivalent
to 3 mol equivalents with reference to the substrate.
However, further increment in the amount of sodium
borohydride to 6 mol equivalent was not much beneficial
in terms of reductive transformation of oxime into amine.
The yield was observed to be high at elevated temperature.
Not much influence of the amount of magnetite nanopar-
ticles was observed on the yield of amine product (Table 1,
entry 4). The effect of solvent on the course of reduction
was also studied and it was observed that the present
reductive system works efficiently in methanol and ethanol.
The results clearly indicate that the presence of a polar
Fig. 4 Size distribution of Fe3O4 nanoparticles
Table 1 Optimization of reaction conditions for benzaldehyde oxime (1 mmol), reaction time 30 min
OH
NH2
NaBH4
N
Fe3O4 NPs
H
Ph
H
Ph
Entry no.
NaBH4 (mmol)
Catalyst (Fe3O4) (mg)
Solvent
Temp. (°C)
Yielda (%)
1
2
3
4
5
6
7
8
9
10
a
1.0
3.0
6.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
5.0
5.0
5.0
10.0
5.0
5.0
5.0
5.0
5.0
5.0
Methanol
Methanol
Methanol
Methanol
Methanol
Methanol
Ethanol
rt
57
80
85
83
88
90
89
75
72
53
rt
rt
rt
40
70
40
40
40
40
Propan-2-ol
Butanol
Tetrahydrofuran
Isolated yields obtained following the general procedure
123

Efficient Reduction of C–N Multiple Bonds Catalyzed by Magnetically Retrievable Magnetite…
Table 2 Reduction of oximes with NaBH4 catalyzed by Fe3O4 nanoparticles
Yielda
(%)
Entry
no.
Substrate
Product
Time
(min)
1
2
30
30
64
NOH
NH2
78b
85
H3C
CH NOH
NH2
CH2
H3C
3
4
5
30
30
40
NH2
CH2
Br
Br
CH NOH
86
81
NH2
CH2
Cl
Cl
CH NOH
C
NOH
NH2
CH2
CH3
CH3
a
Isolated yields obtained following the general procedure
b
The catalyst was recovered magnetically and reused, and the % yield of product is 78, 76, 73, 70 and 68 after 1st, 2nd, 3rd, 4th and 5th run
respectively
Fig. 5 Powder XRD of recovered Fe3O4 nanoparticles
protic solvent favours the reduction as the reaction was
sluggish in tetrahydrofuran. Further, the efficiency of the
present catalytic system could be correlated to the dielec-
tric constants and thereby to the polarity of solvents (Di-
electric Constants at 25 °C- methanol: 32.7, ethanol: 24.5,
Fig. 6 SEM of recovered Fe3O4 nanoparticles
123

P. Kumari et al.
Table 3 Reduction of nitriles with NaBH4 catalyzed by Fe3O4 nanoparticles
Entry
no.
1
Substrate
Product
Time
(min)
30
Yieldb
(%)
CH3–CH2–CN
CH3– CH2–CH2–NH2
72
2
3
4
CH3–CH2–CH2–CN
CH3–CH2–CH2–CH2–NH2
30
30
30
74
87
88
CN
CH2NH2
NH2
NH2
CH2
CH2
H3C
CN
H3C
Cl
5
40
86
Cl
CN
a
Isolated yields obtained following the general procedure
isopropyl alcohol: 19.9, butanol: 17.8, tetrahydrofuran:
7.6). Solvent with high polarity may contribute more
towards the stabilization of reaction intermediates which
are supposed to be more polarized/charged than the reac-
tant molecules and thereby positive impact of solvent has
been observed.
substituted oximes and corresponding amines were iso-
lated and purified by column chromatography. The
products were characterized by the NMR and IR spec-
troscopic data which were in good agreement with the
reported data. The catalyst was separated by using
external magnet and reused five times without any sig-
nificant loss in its activity. The SEM and powder XRD
pattern after fifth cycle of the reaction are shown in
Figs. 5 and 6 which indicate that there is not much
change in the morphology and phase of Fe3O4
nanoparticles. The TEM image of the recovered Fe3O4
The scope and limitations of the present reductive
system were studied by performing the reactions of
different aldoximes and ketoximes with sodium boro-
hydride catalyzed with Fe3O4 nanoparticles (Table 2).
The present catalytic system worked well for different
Fig. 7 TEM image (left), size distribution (right) of recovered Fe3O4 nanoparticles
123

Efficient Reduction of C–N Multiple Bonds Catalyzed by Magnetically Retrievable Magnetite…
Scheme 1 A plausible mechanism for Fe3O4 nanoparticles catalyzed reduction of oximes
nanoparticles also justifies that the shape of nanoparti-
cles remains the same; however, the size distribution has
changed (Fig. 7) which could be attributed to the inter-
action of magnetite with reactant in presence of NaBH4.
The SEAD pattern of recovered nano Fe3O4 also shows
strong reflections at the same (hkl) positions verifying
the pattern for Fe3O4 nanoparticles (Supporting Infor-
mation, Fig. S17).
gives products with high yield and selectivity. The catalyst
is magnetically separable which makes the work up of the
reaction very easy. The catalyst is reusable for more than
five reaction cycles for the conversion of oximes to the
corresponding amine. This method offers some advantages
in terms of clean reaction conditions, recyclability of
castalyst, short reaction times, easy work-up procedure and
suppression of side products.
The reduction of different aliphatic and aromatic nitriles
was also studied by sodium borohydride catalyzed by
magnetite nanoparticles at 40 °C in methanol (Table 3).
High yield of products were obtained under mild conditions.
The present catalytic system exhibited good activity and
selectivity for the reduction of various oximes and nitriles. It
is believed that Fe3? of nano Fe3O4 coordinates to nitrogen
and oxygen of oxime group or nitrogen of cyano group and
thereby makes the carbon of [C=NOH bond or CN bond
more electrophilic to facilitate the attack of hydride ion from
sodium borohydride leading to the formation of imine
intermediate (Scheme 1). Further, imine intermediate gets
reduced to amine product by sodium borohydride in the
presence of nano Fe3O4. The similar interaction of Fen? ion
of Fe3O4 nanoparticles with electronegative atoms such as
nitrogen and oxygen has also be explained in nano Fe3O4
catalyzed synthesis of various oximes and pyrimidine
derivatives [25–27]. Various studies have been reported to
explain the similar course of reductions assisted by transition
metal—NaBH4 system under different conditions whereby
reactant such as nitrile binds to the solid surface of transition
metal compound through nitrogen and thereby facilitating
the attack of hydride ions from borohydride to electrophilic
carbon of CN bond [28, 29].
Acknowledgments Authors acknowledge University of Delhi (In-
novation Project DBC 306/2015-16) and Science and Engineering
Research Board (SERB), New Delhi (Project File No. ECR/2015/
000541) for financial support. Authors are also thankful to University
Science Instrumentation Centre (USIC) & Department of Chemistry,
University of Delhi, New Delhi for spectroscopic data and Desh-
bandhu College, Kalkaji, New Delhi for providing necessary facilities
for the research work.
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