Phospha-Michael addition of diethyl phosphite to α,β-unsaturated malonates catalyzed by nano γ-Fe2O3-pyridine based catalyst as a new magnetically recyclable heterogeneous organic base

Article abstract of DOI:10.1016/j.apcata.2013.01.009

Nano γ-Fe₂O₃-pyridine based catalyst as a new magnetically recyclable heterogeneous organic base was synthesized. The synthesized odorless pyridine based catalyst was used as a new catalyst for the efficient synthesis of β-phosphonom

Full text of DOI:10.1016/j.apcata.2013.01.009

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Applied Catalysis A: General 454 (2013) 145–151
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Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Phospha-Michael addition of diethyl phosphite to ␣,␤-unsaturated
malonates catalyzed by nano ␥-Fe2O3-pyridine based catalyst as a
new magnetically recyclable heterogeneous organic base
Sara Sobhani∗, Mahboobeh Bazrafshan, Amin Arabshahi Delluei, Zahra Pakdin Parizi
Department of Chemistry, College of Sciences, University of Birjand, Birjand 414, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Nano ␥-Fe2O3-pyridine based catalyst as a new magnetically recyclable heterogeneous organic base
was synthesized. The synthesized odorless pyridine based catalyst was used as a new catalyst for the
efficient synthesis of ␤-phosphonomalonates by the reaction of diethyl phosphite with ␣,␤-unsaturated
malonates. The catalyst was easily isolated from the reaction mixture by a magnetic bar and reused at
least 10 times without significant degradation in the activity.
Received 21 October 2012
Received in revised form
30 December 2012
Accepted 10 January 2013
Available online xxx
© 2013 Elsevier B.V. All rights reserved.
Keywords:
␤-Phosphonomalonates
Nanoparticles
Heterogeneous catalyst
Pyridine
Iron oxide
1. Introduction
economical and practical efficient process for catalyst separation
and reuse have been attracted much attention as a central focus
In recent years, extensive efforts have been made to introduce
convenient and efficient methods for the synthesis of phospho-
nates. Direct P C bond formation is the most versatile and powerful
tools for the synthesis of phosphonates. Within the methods
for P C bond formation, phospha-Michael addition has evoked
remarkable attention by organic chemists [1–17]. Synthesis of
␤-phosphonomalonates by this method are most commonly pro-
moted by BrØnsted/Lewis acids [1–3], bases [4–10], transition
metals [11,12], radical initiators [13,14], microwaves [15] or ionic
liquid [17]. Even though, phospha-Michael addition could proceed
by these methods, many of these reagents cannot be reused, and in
many instances, long reaction time, drastic reaction conditions and
sometimes, according to the nature of the catalyst, tedious work-up
is needed. Therefore, the development of a new method to over-
come these short comings still remains an ongoing challenge for
the synthesis of these significant scaffolds.
area in the green chemistry research in 21st century. Heterogeniza-
tion of homogeneous catalysts by their immobilization on various
insoluble supports simplifies the catalyst removal and minimizes
the amount of waste formed. However, although heterogeneous
catalysts can be recovered by filtration or centrifugation methods,
these methods are time consuming and may cause loss of the cata-
lyst. Moreover, a substantial decrease in the activity and selectivity
of the immobilized catalyst is frequently observed due to the het-
erogeneous nature of support materials in reaction media, steric
and diffusion factors [18,19]. Therefore, to maintain economic via-
bility, a suitable heterogeneous system must not only minimize
the production of waste, but should also exhibit activity and selec-
tivity comparable or superior to existing homogeneous routes. In
an attempt to resolve such problems, nanoparticles (NPs) have
been used as alternative matrix for supporting homogeneous cat-
alysts. When the size of the support materials is decreased to the
nanometer scale, the surface area of the NPs might be increased. As
a consequence, NPs could have a higher catalyst loading capacity
and a higher dispersion than many conventional support matrices,
leading to an improved catalytic activity of the supported catalysts.
However, conventional separation methods may become ineffi-
cient for support particle sizes below 100 nm. The use of magnetic
NPs (MNPs) such as iron oxide as supporting materials offers a
solution to this problem [20–22]. MNPs are easily separated by
an external magnet. The magnetic separation of MNPs is simple,
In the past decades, much attention has been paid to research
dedicated to the development of environmentally compatible
processes. Along with this awareness; industries have started
implementing safer practices such as waste prevention using new
catalysts. In this view, the design of environmentally benign, an
∗
Corresponding author. Tel.: +98 561 2502065; fax: +98 561 2502065.
E-mail addresses: sobhanisara@yahoo.com, ssobhani@birjand.ac.ir (S. Sobhani).
0926-860X/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.apcata.2013.01.009

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S. Sobhani et al. / Applied Catalysis A: General 454 (2013) 145–151
mixture was refluxed for 18 h. The solid material was then filtered,
washed with water, methanol, CH2Cl2 and dried at room temper-
ature in vacuum to afford nano ␥-Fe2O3-pyridine based catalyst
1.
2.2. Back titration analysis of catalyst 1
Scheme 1. ␥-Fe2O3-pyridine based catalyst 1.
HCl solution (10 mL, 0.1 M) was added to the catalyst (100 mg) in
an Erlenmeyer flask. Excess amount of the acid was neutralized by
addition of NaOH solution (0.1 M) to the equivalence point of titra-
tion. The required volume of NaOH to this point was 9.76 mL. The
amount of pyridine functionalized on ␥-Fe2O3@SiO2 is evaluated
economical and promising for industrial applications. It is also typ-
ically more effective than filtration or centrifugation as it prevents
loss of the catalyst.
to be 0.24 mmol g−1
.
Pyridine is a well-known liquid organic base, which is used as an
active catalyst in organic syntheses. However, its separation from
homogeneous reaction mixtures requires neutralization by acidic
conditions which lead to worthless pyridinium salts. The best way
to avoid the harmful effect of acidic work-up is supporting pyri-
dine on a solid surface [23]. Supporting provides the reusability of
pyridine and eliminates the unpleasant fish-like odor of pyridine.
Due to the importance of the synthesis of supported pyridine
on the solid surface and characteristic properties of nano magnetic
iron oxides as supporting material, in this paper, we have synthe-
sized nano ␥-Fe2O3-pyridine based catalyst 1 (Scheme 1) as a new
odorless pyridine based catalyst. We have also used it as a magnet-
ically recyclable heterogeneous basic catalyst for the synthesis of
␤-phosphonomalonates via Michael addition of dialkyl phosphites
to ␣,␤-unsaturated malonates.
2.3. General procedure for Michael addition of diethyl phosphite
to ˛,ˇ-unsaturated malonates catalyzed by nano
ꢀ-Fe2O3-pyridine based catalyst 1
Catalyst 1 (5 mol%) was added to a mixture of ␣,␤-unsaturated
malonate (5 mmol) and diethyl phosphite (10 mmol). The mixture
was stirred at 70 ◦C for the appropriate time (Table 2). The cat-
alyst was separated by a magnetic bar from the cooled mixture,
washed with EtOH, dried 30 min at 110 ◦C and reused for a consec-
utive run under the same reaction conditions. Evaporation of the
solvent of the remaining solution under reduced pressure gave the
crude products. The pure products (2–18, Table 2) were isolated by
chromatography on silica gel eluted with n-hexane:EtOAc (1:2).
2.4. Typical procedure for the use of nano ꢀ-Fe2O3-pyridine
based catalyst 1 in multiple sequential synthesis of
ˇ-phosphonomalonate 2
2. Experimental
2.1. Large scale synthesis of nano ꢀ-Fe2O3-pyridine based
catalyst 1
Catalyst 1 (5 mol%) was added to a mixture of benzyliden-
malononitrile (5 mmol) and diethyl phosphite (10 mmol). The
mixture was stirred at 70 ◦C for 1 h. New samples of benzyliden-
emalononitrile (5 mmol) and diethyl phosphite (10 mmol) were
added to the reaction mixture (ten times) and each time the reac-
tion mixture was stirred at 70 ◦C for 1 h. After separation of the
catalyst from the cooled mixture by a magnetic bar, the solvent
was evaporated to give a crude product. The pure product 2 was
isolated in 83% yield by chromatography on silica gel eluted with
n-hexane:EtOAc (1:2).
The ␥-Fe2O3 nanoparticles were synthesized by a reported
chemical co-precipitation technique of ferric and ferrous ions
in alkali solution with minor modifications [24–26]. FeCl2·4H2O
(3.68 g) and FeCl3·6H2O (10 g) were dissolved in deionized
water (300 mL) under Ar atmosphere at room temperature. A
NH4OH solution (25%, 100 mL) was then added drop wise (drop
rate = 1 mL min−1) to the stirring mixture at room temperature
to reach the reaction pH to 11. The resulting black dispersion
was continuously stirred for 1 h at room temperature and then
heated to reflux for 1 h to yield a brown dispersion. The mag-
netic nanoparticles were then purified by a repeated centrifugation
(1730–3461 g, 20 min), decantation, and redispersion cycle 3 times.
The as-synthesized sample was heated in air at 2 ◦C min−1 up to
200 ◦C and then kept in the furnace for 3 h to give a reddish-brown
powder.
Concentrated solution of ammonia was then added to the dis-
persed ␥-Fe2O3 nanoparticles (8.5%, w/w, 20 mL) in methanol
(80 mL) and the resulting mixture was stirred at 40 ◦C for 30 min.
Subsequently, tetraethyl orthosilicate (TEOS, 1.0 mL) was charged
to the reaction vessel, and the mixture was continuously stirred at
40 ◦C for 24 h. The silica-coated nanoparticles (␥-Fe2O3@SiO2) were
collected by a permanent magnet, followed by washing 3 times
with EtOH and diethyl ether and dried at 100 ◦C in vacuum for 24 h.
A mixture of ␥-Fe2O3@SiO2 (2 g) in toluene (40 mL) was soni-
cated for 30 min. 3-Mercaptopropyl trimethoxysilane (0.5 mL) was
added to the dispersed ␥-Fe2O3@SiO2 in toluene and slowly heated
to 105 ◦C and stirred at this temperature for 20 h. The resulting
mercapto-functionalized ␥-Fe2O3@SiO2 was separated by an exter-
nal magnet and washed 3 times with methanol, ethanol and CH2Cl2
and dried under vacuum. 3-(Chloromethyl)pyridine hydrochloride
(0.15 g) and triethylamine (0.13 mL) were added to mercapto-
functionalized ␥-Fe2O3@SiO2 (1.7 g) in dry toluene (15 mL), and the
3. Results and discussion
3.1. Synthesis of nano ꢀ-Fe2O3-pyridine based catalyst 1
At first, ␥-Fe2O3 NPs were synthesized by a chemical co-
precipitation technique of ferric and ferrous ions in alkali solution
[24–26]. Fig. 1 shows the XRD pattern of ␥-Fe2O3 NPs. Diffraction
о
о
о
о
о
peaks at around 2ꢁ = 30.4 , 35.8 , 43.6 , 53.7 , 57.6◦, 63.2 cor-
responding to the (2 2 0), (3 1 1), (4 0 0), (4 2 2), (5 1 1) and (4 4 0)
are readily recognized from the XRD pattern. The observed diffrac-
tion peaks agree with the cubic structure of maghemite (JCPDS
file No 04-0755) with a unit cell dimension of 0.835 nm and the
space group of P4132 (213). The average crystallite size was cal-
culated to be 13.1 nm using the Scherrer equation in which K = 0.9
and ꢂ = 0.154 nm.
Ultimately, sonication of ␥-Fe2O3 NPs suspension in an alka-
line solution of tetraethyl orthosilicate (TEOS) caused coating of
the magnetic cores with silica shells. The outer shell of silica not
only improves the dispersibility but also provides suitable sites
(Si-OH groups) for further surface functionalization. The result-
ing silica-coated ␥-Fe2O3 NPs (␥-Fe2O3@SiO2) were then allowed
to react with an appropriate concentration of 3-mercaptopropyl
trimethoxysilane to give mercapto-functionalized silica-coated

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S. Sobhani et al. / Applied Catalysis A: General 454 (2013) 145–151
147
1)
1
(3
2200
2000
1800
1600
1400
1200
(4
4
0
)
0)
(
5
1
1
)
0
(4
(
4
2
2
)
30
40
50
60
70
o
2 Theta ( )
Fig. 1. XRD pattern of ␥-Fe2O3 NPs.
␥-Fe2O3. To this end, the obtained mercapto-functionalized ␥-
Fe2O3@SiO2 was subjected to react with 3-(chloromethyl)pyridine
hydrochloride to obtain nano ␥-Fe2O3-pyridine based catalyst 1.
Fig. 2. SEM image of catalyst 1.
␥-Fe2O3@SiO2. This band which is related to the stretching vibra-
tion of S H bonds is disappeared in the spectra of catalyst 1. The
peaks placed at 626 and 1062 cm−1 are related to the stretch-
ing vibrations of Fe O and Si O bonds, respectively. These two
peaks are also observed in the FT-IR spectra of ␥-Fe2O3@SiO2
and mercapto-functionalized ␥-Fe2O3@SiO2. The strong and broad
band in the range of 3147–3504 cm−1 corresponds to the hydrogen
bonded Si OH groups and adsorbed water. Another broad band at
1612 cm−1 is also due to the OH vibration of adsorbed water.
3.2. SEM and HRTEM
The size and structure of nano ␥-Fe2O3-pyridine based catalyst 1
were evaluated using scanning electron microscopy (SEM) and high
resolution transmission electron microscopy (HRTEM). The SEM
image of the supported catalyst showed uniformity and spherical
morphology of nanoparticles (Fig. 2). The aggregation gives rise to
increase the size of observed nanoparticles with an average diam-
eter of ca. 63 nm. Fig. 3 shows HRTEM of nano ␥-Fe2O3-pyridine
based catalyst 1 which further confirmed an assembly of the cat-
alyst and its size is less than 13 nm. HRTEM image of the catalyst
demonstrates the core-shell structure of the particles and confirms
the presence of the silica coating (Fig. 3b). This observation is in
agreement with reducing surface area calculated by BET method
for catalyst 1 (56 m2 g−1) compared with ␥-Fe2O3 (91 m2.g−1). It
is worth to note that reducing surface area is also a consequence
of incorporation of organic spacer containing pyridine groups onto
the surface of nanoparticles.
3.4. Thermo-gravimetric analysis (TGA)
The thermal behavior of nano ␥-Fe2O3-pyridine based catalyst 1
is shown in Fig. 5. A significant decrease in the weight percentage of
catalyst1 atabout150 ◦Cis relatedtodesorptionofwatermolecules
from the catalyst surface. This was evaluated to be ∼0.07% accord-
ing to the TG analysis. Another decreasing peak started at 279 ◦C
and exhibits high thermostability of the catalyst. The organic parts
decomposed completely at around 800 ◦C. According to the TGA,
the amount of pyridine functionalized on ␥-Fe2O3@SiO2 calcu-
lated to be 0.25 mmol g−1. These results are in agreement with
back titration and elemental analysis (N = 0.35 and C = 2.5%). The
average number of pyridine attached to one NP evaluated to be
2.27 × 10−18 mmol per one NP [27]. It was calculated using sur-
face area (obtained from BET method), the amount of pyridine
3.3. FT-IR spectra
In the FT-IR spectra of catalyst 1 (Fig. 4), characteristic absorp-
tion bands due to the ring stretching vibrations of C C and C N are
observed at 1325–1436 cm−1. An absorption band at 2624 cm−1
is observed in the FT-IR spectra of mercapto-functionalized
Fig. 3. HRTEM images of catalyst 1.

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S. Sobhani et al. / Applied Catalysis A: General 454 (2013) 145–151
Table 1
Michael addition of diethyl phosphite to benzylidenmalononitrile under different conditions.
Entry
Catalyst
Molar ratio (%)
Reaction temperature (◦C)
Reaction time (h)
Yield of product 2a (%)
1
2
3
4
5
6
Catalyst 1
Catalyst 1
Catalyst 1
Catalyst 1
–
5
3
1
5
–
5
70
70
70
r.t.
70
70
1
1.5
3
6
24
24
85
70
70
40
60
65
␥-Fe2O3@SiO2
a
Isolated yield. Conditions: benzylidenmalononitrile (1 mmol), diethyl phosphite (2 mmol).
functionalized on catalyst 1 (obtained from TGA) and average dime-
ter of nanoparticles (obtained from HRTEM image).
[28], heterogeneous catalysts {H3PMo12O40 [29], HClO4/SiO2 [30],
nano n-propylsulfonated ␥-Fe2O3 (NPS-␥-Fe2O3) [31]} and 5-
hydroxypentylammonium acetate (5-HPAA) [32] as an ionic liquid
for the synthesis of ␤-phosphonomalonates. In these reactions,
due to the use of acidic or neutral conditions, malodorous tri-
alkyl phosphite was used as the phosphorus compound. In one
report, we have synthesized ␤-phosphonomalonates using amino-
propylated silica (AP-SiO2) [33] as a basic catalyst in the presence
of dialkyl phosphite as an odorless phosphorus nucleophile. In
this connection, in order to show the merit of synthesized nano
␥-Fe2O3-pyridine based catalyst 1 as magnetically recyclable het-
erogeneous catalyst in organic synthesis, we have studied Michael
addition of dialkyl phosphites to ␣,␤-unsaturated malonates in the
presence of this newly synthesized organic base.
3.5. Catalytic activity of nano ꢀ-Fe2O3-pyridine based catalyst 1
for the synthesis of ˇ-phosphonomalonates
As part of our efforts directed toward the development of
new methods for the synthesis of phosphonate derivatives, we
have recently introduced micellar solution of sodium stearate
At first, reaction of diethyl phosphite to benzylidenmalonon-
itrile was chosen to optimize the reaction conditions such as
temperature and molar ratio of the catalyst (Scheme 2, Table 1).
We found that in the presence of 5 mol% of nano ␥-Fe2O3-
pyridine based catalyst 1, the best yield of the corresponding
␤-phosphonomalonate was obtained at 70 ◦C (Entry 1). In order to
show the role of the catalyst, similar reactions in the absence of the
catalyst and in the presence of nanomagnetic ␥-Fe2O3@SiO2 were
also examined. Under these conditions, the reactions led to the for-
mation of the desired product in low yields after a long reaction
time (Entries 5 and 6). A reaction of banzaldehyde, malononitrile
and diethyl phosphite in the presence of catalyst 1 (5 mol%) at 70 ◦C
produced the desired product in 20% yield after 1 h.
The reaction of diethyl phosphite with different ␣,␤-
unsaturated malonates in the presence of nano ␥-Fe2O3-pyridine
based catalyst 1 under the best reaction conditions was then
investigated. The results of this study are depicted in Table 2.
As indicated in Table 2, phospha-Michael addition of diethyl
phosphite with benzylidenemalononitriles substituted with dif-
ferent electron-donating and electron-withdrawing groups pro-
ceeded well and the corresponding ␤-phosphonomalonates in
71–96% yields were obtained (Entries 1–11). The catalyst was
compatible with functional groups such as Cl, Br and O-Me. No
competitive nucleophilic methyl ether cleavage was observed for
the substrates which possessed an aryl-O-Me group (Entries 2 and
3), despite the strong nucleophilicity of phosphites. The reaction
of diethyl phosphite with ␣,␤-unsaturated malonates substituted
with heteroaromatic groups worked well to produce the desired
products in good to high yields (Entries 12 and 13). The method
is also applicable for the synthesis of ␤-phosphonomalonates
from the reaction of diethyl phosphite with ␤,␤-disubstituted
malonates (Entries 14 and 15). The applicability of this method
was also studied for the phospha-Michael addition to some other
3440
2940
2440
1940
1440
940
440
Wavelength (cm-1)
γ-Fe2O3@SiO2
mercapto-functionalized γ-Fe2O3@SiO2
catalyst 1
Fig.
4. FT-IR
␥-Fe2O3@SiO2 and catalyst 1.
spectra
of
␥-Fe2O3@SiO2,
mercapto-functionalized
100
99
98
97
96
95
94
o
279
C
99.03%
o
813
C
94.83%
O
O
CN
CN
CN
CN
(EtO)2P
Ph
catalyst
HP(OEt)2
+
100
200
300
400
500
600
700
800
Temperature oC
Ph
Fig. 5. TGA diagram of catalyst 1.
Scheme 2. Michael addition of diethyl phosphite to benzylidenmalononitrile.