Magnetic nano-Fe3O4-supported 1-benzyl-1,4- dihydronicotinamide (BNAH): Synthesis and application in the catalytic reduction of α,β-epoxy ketones

Article abstract of DOI:10.1021/ol203423u

A novel magnetically recoverable organic hydride compound was successfully constructed by using silica-coated magnetic nanoparticles as a support. An as-prepared magnetic organic hydride compound, BNAH (1-benzyl-1,4- dihydronicotinamide), showed efficient activity in the catalytic reduction of α,β-epoxy ketones. After reaction, the magnetic nanoparticle- supported BNAH can be separated by simple magnetic separation which made the separation of the product easier.

Full text of DOI:10.1021/ol203423u

ORGANIC
LETTERS
2012
Vol. 14, No. 5
1210–1213
Magnetic Nano-Fe3O4-Supported
1-Benzyl-1,4-dihydronicotinamide
(BNAH): Synthesis and Application in the
Catalytic Reduction of r,β-Epoxy Ketones
Hua-Jian Xu,*,† Xin Wan,† Yong-Ya Shen,‡ Song Xu,† and Yi-Si Feng*,‡
School of Medical Engineering, School of Chemical Engineering, Hefei University of
Technology, Hefei 230009, P. R. China
hjxu@hfut.edu.cn; ysfeng@hfut.edu.cn
Received December 22, 2011
ABSTRACT
A novel magnetically recoverable organic hydride compound was successfully constructed by using silica-coated magnetic nanoparticles as a
support. An as-prepared magnetic organic hydride compound, BNAH (1-benzyl-1,4-dihydronicotinamide), showed efficient activity in the catalytic
reduction of R,β-epoxy ketones. After reaction, the magnetic nanoparticle-supported BNAH can be separated by simple magnetic separation
which made the separation of the product easier.
In recent years, organic hydride compounds has at-
tracted more attention due to the catalytic reduction of
various substrates by hydride transfer. There are many
natural organic hydride compounds, such as nicotinamide
adenine dinucleotide (NADH) and its phosphate deriva-
tive (NADPH), flavin adenine dinucleotide (FADH), vi-
tamins C and E, coenzyme F420, and so on. NADH (or
NADPH) is a very famous biological catalyst which has
been used widely in biological redox reactions.1 Due to
much effort from various research groups, it is already
clear that NADH acts as a coenzyme in hydrogenation
reactionsand the activecore is 1,4-dihydropyridine. There-
fore, a number of NADH models with this core, such as
BNAH, Hantzsch ester (HEH), and 10-methyl-9,10-
dihydroacridine (AcrH2) have been successfully synthesized
and appliedinorganicsynthesis.2 Theyand their analogues
are already known to reduce R,β-unsaturated aldehydes
or ketones, activated olefins, imines, R,β-epoxy ketones,
β-nitroacrylates, and tertiary amides, alone or accompanied
by other catalysts.3
(3) For precedent reviews and selective highlights on hydrogenation,
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2008, 3, 1750–1770. (e) Rueping, M.; Sugiono, E.; Schoepke, F. R.
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S.; Tanaka, T. J. Am. Chem. Soc. 1989, 111, 1497–1499. (j) Zhu, X. Q.;
Liu, Y. C. J. Org. Chem. 1998, 63, 2786–2787. (k) Li, J.; Liu, Y. C.; Deng,
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† School of Medical Engineering.
‡ School of Chemical Engineering.
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10.1021/ol203423u
Published on Web 02/10/2012
2012 American Chemical Society

Despite their wide employment,3ꢀ5 their separation is
very difficult due to the homogeneous reaction system.
Recently, to address this problem effort has been focused
mainly on loading the homogeneous catalyst on some solid
supports.6 Polymer (Merrifield resin)7 and SiO28 are pop-
ular solid supports in the immobilization of organic
hydride compounds in the past few decades. However,
Merrifield resin is affected largely by solvent and SiO2
often leads to the low reactivity of organic hydride com-
pounds. To solve these problems, Zhu et al. reported the
synthesis of polysiloxane-BNAH and its application in the
reduction of some activated olefins.9 Meanwhile, magnetic
separation provides a very convenient approach for re-
moving and recycling magnetic nanoparticles (MNPs)
with an external magnet. Recently, the MNPs have been
served as highly promising supports of organocatalysts in
some prestigious work. DMAP, a phase-transfer catalyst,
and aa chiral catalyst which show high catalytic properties
and recyclabilities have been developed successfully and
used in organic reactions.10 However, to the best of our
knowledge, no example of an MNP-supported organic
hydride compound was discovered. Herein, we reported
the catalytic reduction of R,β-epoxy ketones with a mag-
netically recoverable MNPs-BNAH for the first time.
Magnetite nanoparticles (Fe3O4) and silica-coated mag-
netite nanoparticles (Fe3O4@SiO2) were selected as sup-
ports, with the former prepared by coprecipitation11 and
Figure 1. XRD pattern of 2. The bottom row of tick marks
indicates the reflection positions for a standard magnetite
pattern (JCPDS no. 00-002-1035).
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8608–8610. (h) Ohkubo, K.; Nanjo, T.; Fukuzumi, S. Org. Lett. 2009, 7,
4265–4268. (i) Xu, H. J.; Lin, Y. C.; Wan, X.; Yang, C. Y.; Feng, Y. S.
Tetrahedron 2010, 66, 8823–8827.
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Levacher, V.; Queguiner, G.; Bourguignon, J. Tetrahedron 2001, 57,
3087–3098. (b) He, R.; Toy, P. H.; Lam, Y. Adv. Synth. Catal. 2008, 350,
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Ohno, A. Bull. Chem. Soc. Jpn. 1987, 60, 2423–2427. (b) Fujii, M. Bull.
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2011, 67, 318–325.
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(10) For precedent reviews and the newest reports, see: (a) Shylesh,
Figure 2. TEM images of MNPs-BNAH 1 aggregation (a) as
well as Fe3O4 (b) and Fe3O4@SiO2 (c) nanoparticles.
€
S.; Schunemann, V.; Thiel, W. R. Angew. Chem., Int. Ed. 2010, 49, 3428–
the latter prepared according to the literature.12 BNAH
was covalently immobilized onto the surface of the MNPs
by forming FeꢀSiꢀO or SiꢀOꢀSi bond between MNPs
and 3-aminopropyltriethoxysilane (APTS) (Scheme 1).
The loading steps proceeded cleanly and could be mon-
itored quantitatively by elemental analysis; the loadings
of MNPs-BNAH 1 and 2 were determined to be 0.52 and
0.57 mmol/g, respectively.
3459 and references therein. (b) Lim, C. W.; Lee, I. S. Nano Today 2010,
5, 412–434 and references therein. (c) Zeng, T. Q.; Yang, L.; Hudson, R.;
Song, G. H.; Moores, A. R.; Li, C. J. Org. Lett. 2011, 13, 442–445. (d)
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Biomol. Chem. 2009, 7, 2669–2677.
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X. P. Chin. J. Chem. 2000, 18, 834–837.
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Zhang, X. M. Adv. Mater. 2006, 18, 3289–3293.
Org. Lett., Vol. 14, No. 5, 2012
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Table 1. Hydrogenation of R,β-Epoxy Ketones to β-Hydroxy Ketones Catalyzed by 2
a Reaction conditions: R,β-epoxy ketones (0.5 mmol), Na2CO3 (2.5 mmol), Na2S2O4 (1.5 mmol), and 2 (0.025 mmol, 44 mg) in 10 mL of AcOEt/H2O
(v/v = 1:1), 6 h, rt, under argon atmosphere. Isolated yield.
According to our previous work,3q MNPs-BNAH was
examined in the reduction of phenyl(3-phenyloxiran-2-
yl)methanone (Scheme 2) and 2 showed higher catalytic
activity than 1. The reason may be the slight aggregation
of bare Fe3O4 nanoparticles of 1, which influenced the
activity (Figure 2a). Therefore, 2 was selected for further
investigation.
The crystalline structure of 2 was characterized by X-ray
diffraction (XRD). The diffraction pattern showed char-
acteristic peaks, and the relative intensity matched well
with those of standard Fe3O4 nanoparticles (JCPDS card
no. 00-002-1035, Figure 1). Moreover, we also could see
the peaks of amorphous silica from 2θ = 20° to 30°. It was
demomstrated roughly that the Fe3O4 nanoparticles were
successfully coated with SiO2. Transmission electron mi-
croscope (TEM) analysis (Figure 2b and c) of the Fe3O4
and Fe3O4@SiO2 nanoparticles showed a uniform-sized
dark Fe3O4 nanoparticles core with an average size range
of 10ꢀ16 nm surrounded by a gray silica shell about 8ꢀ10 nm
thick. And TG curves confirmed the anchoring of BNAH on
MNPs (see Supporting Information).
As shown in Table 1, a series of R,β-epoxy ketones were
investigated; the corresponding hydrogenation products
β-hydroxyketones were obtained with good to excellent
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Org. Lett., Vol. 14, No. 5, 2012

Table 2. Recyclable Experiments of 2
Scheme 1. Preparation of MNPs-BNAH
2 (5 mol %)
AcOEt=H2O (1 : 1)
3l
4l
f
Na2S2O4, Na2CO3
Ar, hv, rt, 6 h
cycle
1
2
3
4
5
6
yield (%)
98
97
97
94
93
90
system,3q a more simple separation of MNPs-BNAH
could be achieved in our current protocol.
For practical application to heterogeneous systems, the
lifetime of MNPs-BNAH and their level of reusability are
very important factors. To clarify this issue, we established
a set of experiments for the catalytic hydrogenation of
4-bromophenyl-3-phenyloxiran-2-yl-methanone (3l) with
2. It was shown that 2 could be used at least six times with
little change in the activity (Table 2).
In conclusion, we have developed the first example of
an MNP-supported organic hydride compound, BNAH,
which was used in the catalytic hydrogenation of R,β-
epoxy ketones. Between as-prepared MNPs-BNAH 1
and 2, 2 demonstrated higher activity in the reaction and
could be recycled six times with little loss in activity. Due to
their low toxicity, easy separation from the reaction system
with an external magnet, and the sustained activity in
recyclable processes, such a magnetic particle is a potential
alternative in both laboratory research and scale production.
Scheme 2. Comparation of Catalytic Activity of 1 and 2
yields, catalyzed by 2. When R1 and R2 were aryl or
heteroaryl, the substituent and steric effect were not very
visible in this system (3aꢀp). The yield would decrease
slightly when R1 was an aliphatic substituting group (3q).
Moreover, a series of imines were also tried; unfortunately,
no reaction was observed in the current system. It is known
that imines could not be reduced directly by BNAH, which
is in accord with the results reported by Zhu et al.13
Easy and rapid separation by magnetism is the most
advantageous feature of MNPs-BNAH. It was concen-
trated on the sidewall of a reaction vessel with an external
magnet after the reaction, and the aqueous and organic
phases were separated by magnetic decantation. Com-
pared with our previous report that free BNAþBrꢀ or
BNAH cannot be separated from the homogeneous
Acknowledgment. We gratefully acknowledge financial
support from the National Natural Science Foundation of
China (Nos. 20802015, 21072040, 21071040) and the
Program for New Century Excellent Talents in University
of the Chinese Ministry of Education. We thank Prof.
Shou-Hu Xuan from the University of Science and Tech-
nology of China for valuable discussions on the prepara-
tion of catalysts. We also thank Qiang Huang in this group
for reproducing the results of compounds 3a, 3e, and 3h.
Supporting Information Available. Synthesis and char-
acterizations of MNPs-supported BNAH and copies of
1H and 13C NMR spectra for the products in Table 1.
These materials are available free of charge via the
Internet at http://pubs.acs.org.
(13) (a) Zhu, X. Q.; Zhang, M. T.; Yu, A.; Wang, C. H.; Cheng, J. P.
J. Am. Chem. Soc. 2008, 130, 2501–2516. (b) Zhu, X. Q.; Liu, Q. Y.;
Chen, Q.; Mei, L. R. J. Org. Chem. 2010, 75, 789–808.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 5, 2012
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