Highly efficient solvent free synthesis of α-aminophosphonates catalyzed by recyclable nano-magnetic sulfated zirconia (Fe3O4@ZrO2/SO42-)

Article abstract of DOI:10.1039/c5ra13173a

In this project, nano-magnetic sulfated zirconia Fe₃O₄@ZrO₂/SO₄^2- was prepared and characterized using various instrumental methods. Sulfated zirconia supported on magnetic nanoparticles can act as a well-organized nanocatalyst and can be easily separated from the reaction mixture using an external magnetic field. Nano-Fe₃O₄@ZrO₂/SO₄^2- is a heterogeneous acidic catalyst and has particular advantages such as a facile synthesis procedure, high activity, easy separation and reusability. It was applied as an efficient nanocatalyst in the synthesis of α-aminophosphonate derivatives in the Kabachnik-Fields reaction. This synthetic method has several advantages including high yields, short reaction times, easy workup and environmentally benign reaction conditions.

Full text of DOI:10.1039/c5ra13173a

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: H. Ghafuri, A.
Rashidizadeh and H. R. Esmaili Zand, RSC Adv., 2016, DOI: 10.1039/C5RA13173A.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 11
RSC Advances
View Article Online
DOI: 10.1039/C5RA13173A
RSC advance
ARTICLE
Highly efficient solvent free synthesis of αꢀ
aminophosphonates catalyzed by recyclable
52cv5[Cite this: DOI:
10.1039/x0xx00000x
nano
magnetic
sulfated
zirconia
2ꢀ
(Fe3O4@ZrO2/SO4 )
Hossein Ghafuri*a, Afsaneh Rashidizadeha and Hamid Reza Esmaili Zanda
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
2-
In this project, the nano magnetic sulfated zirconia Fe3O4@ZrO2/SO4 was prepared and characterized
www.rsc.org/
by various instrumental methods. Sulfated zirconia supported on magnetic nanoparticles can act as a
well-organized nanocatalyst also can be easily separated by the external magnetic field from the
2-
reaction mixture. Nano Fe3O4@ZrO2/SO4 is heterogeneous acidic catalyst and has special advantages
such as facile synthesis procedure, high activity, easy separation and reusability. It was applied as an
efficient nanocatalyst in the synthesis of
α-aminophosphonate derivatives in Kabachnik-Fields
reaction. These synthetic methods has several advantages including high yields, short reaction times,
easy workup and environmentally benign reaction conditions.
substrates cause to some advantages such as smooth and easy
process reaction conditions, pureproducts, increased selectivity,
Introduction
αꢀaminophosphonates are structurally similar to αꢀamino acids
and also they are important class of compounds in medicinal
chemistry which are involved in the metabolism of αꢀamino
acids.1ꢀ3 αꢀaminophosphonates have some biological
applications such as antiꢀcancer drugs, strong antibiotics,
nervous system activator, antibody production and antiꢀclotting
agent.
For the first time, Arbuzov produced alkyl phosphonates from
the reaction of trialkyl phosphates with alkyl halides. In 1982
Osipova understand that Nꢀ alkoxy αꢀaminophosphonates can
be produced by nucleophiles addition of trimethyl phosphates
to oximes which converted to αꢀaminophosphonates after one
setp reduction. Some of disadvantages like low yields which
could be mentioned.4 In 1992, Genet obtained αꢀ
aminophosphonates by using trialkyl phosphite.5 Kabachnikꢀ
Fields three component reaction includes the one pot
condensation of the amine, aldehyde and di or triꢀalkyl
Phosphite.3,7ꢀ15 Padvyk reaction in which the dialkyl phosphites
to imine in the presence of a Lewis acid or a base is done.16ꢀ24
Most catalysts used in the synthesis of αꢀaminophosphonates
have shortcomings such as high cost, the use of stoichiometric
amounts of catalyst, sensitivity to moisture and difficulties of
separation and the recycling. Using of reagents on mineral
reduce byꢀproduct and waste generated, the speed of response
and recovery capabilities, recommended as catalysts.3,11,25
Antimony trichloride stabilized on aluminum oxide bed is one
of the example of catalyst which recently used in Kabachnikꢀ
Fields reaction in acetonitrile and under reflux condition.26
Using microwave irradiation is the other method for the
synthesis of αꢀaminophosphonate, which was done under
totally different conditions.27 AmberliteꢀIR 120 resin is used as
a heterogeneous catalyst in many chemical reactions, including
the preparation of αꢀaminophosphonates under microwave
irradiation.28
Using heteropolyacid as catalyst for efficient and green
condition have been reported in many heterogeneous reactions.
These classes of compounds are ecoꢀfriendly, reusable, nonꢀ
toxic and easily removed. Producing αꢀaminophosphonates in
the presence of H3PW12O40 as catalysts by using trimethyl
Phosphite in CH2Cl2 at room temperature is also reported.29, 30
Tosyl chloride in catalyst amount used in the preparation αꢀ
aminophosphonates in CH2Cl2 in the presence of alcohols and
in the room temperature. One of the weaknesses of this catalyst
is nonꢀrecyclability.31Hydrous zirconium chloride at 35°C and
under solventꢀfree conditions or in temperatures above 80°C
This journal is © The Royal Society of Chemistry 2013
Organic Chemistry Frontiers., 2013, 00, 1-3 | 1

RSC Advances
Page 2 of 11
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C5RA13173A
2ꢀ
and
a
shorter duration, can be catalyzed the αꢀ From the FTIR spectrum of Fe3O4@ZrO2/SO4 in figure 2, a
aminophosphonate synthesis. 32
broad peak around 3400 cmꢀ1 has been seen that can be
The other new method for the synthesis of these materials that attributed to the OH stretching vibration. This peak is related to
has been developed, using a catalytic amount of sulfonium the absorption of water molecules on the catalyst surface that
bromide. In the presence of this catalyst the reaction is carreid cause to broadening of hydrogen bond. A peak around 1630
out with a short time, low temperature and high efficiency. cmꢀ1 is related to the bending mode of H2O bonds.
But is limited to aliphatic aldehydes.33 In other work on the
synthesis of αꢀaminophosphonate is using sulfamic acid as a
heterogeneous and recyclable catalyst.34 Another method for
this synthesis is the usage of magnesium ferrite magnetic
nanoparticles as the catalyst. The catalyst is reusable and can be
easily separated from the reaction mixture.35 The use of
magnetic nanoparticles catalyst coated with dehydroascorbic
acid as a heterogeneous catalyst with magnetism properties and
the recent approach is recyclability in the synthesis of αꢀ
aminophosphonates.36 αꢀaminophosphonates are also prepared
by Mg(ClO4)2.37
Recycling problem of bronsted acids and lewis acids cause to
use these only for one time. The separation of them from the
reaction environment is difficult and causes to remaining of
impurities in the reaction. In continuation of our previous
2-
Figure 1: The X-ray diffraction patterns of Fe3O4 and Fe3O4@ZrO2/SO4
research on the development of new synthetic methods of nano
A strong peak for stretching vibration of S=O was appeared in
magnetic sulfated zirconia as a solid acid catalyst in organic
1126
cmꢀ1 and a peak in 1400 cmꢀ1 can be attributed to
38ꢀ39
synthesis,
here in, we investigated the catalytic properties
asymmetric stretching vibration of S=O covalent bond. Peaks
around 1600 cmꢀ1 was appeared in ZrꢀO bond and the
absorption at 500 cmꢀ1 is related to FeꢀO bond.
2ꢀ
of Fe3O4@ZrO2/SO4 in the KabachnikꢀFields reaction which
in this case in addition of the benefits of having a super acid
catalyst and heterogeneous catalyst, ease recovery and can be
resolved the separation difficulties by using magnetic property.
To assess the efficiency of the synthesized catalyst, it was
applied in the KabachnikꢀFields reaction for the synthesis of αꢀ
aminophosphonates, three component KabachnikꢀFields
reaction between 2ꢀchlorobenzaldehyde, aniline and dimethyl
phosphite as a model reaction in the presence of nano magnetic
sulfated zirconia.
Fe3O4
ZrO2
Fe3O4@ZrO2
2-
Fe3O4@ZrO2 SO4
R2
O
O
NH
2ꢀ
Fe3O4 @ZrO2/SO4
R2NH2
P
+
+
O
R1
MeO
OMe
R
R
P
Solventꢀfree
800C
Scheme1. Kabachnik-Fields reaction by using nano magnetic sulfated zirconia
Wave Number (cmꢀ1)
H
R1
OMe
OMe
2-
Figure 2: FT-IR spectra of the Fe3O4, ZrO2, Fe3O4@ZrO2 and Fe3O4@ZrO2/SO4
2-
Fe3O4@ZrO2/SO4
Scanning electron microscope (SEM) image can be provided
information about the size and morphology of the catalyst
structure. SEM in figure 3 has shown that the catalyst structure
is uniform. Its constituent particles are roughly the same size
and the average particle size is about 30 nm. Particle size
distribution curve obtained by scanning electron microscope
image shows the average size of 40ꢀ30 nm for 200 particles.
The graphs were plotted using Excel software (figure 4).
Result and discussion
Catalyst characterization
Six characteristic peaks of Fe3O4 (2θ = 30.1, 35.4, 43.0, 53.5,
57.0 and 62.5) and three diffraction peaks of ZrO2 (30.6, 51.1,
60.1) can be seen in XRD patterns in figure 1. In XRD pattern
2ꢀ
of Fe3O4@ZrO2/SO4
,
Fe3O4 peaks of synthesized
Fe3O4@ZrO2/SO42ꢀ can be observed which no change in peak’s
2ꢀ
position during the production of Fe3O4@ZrO2/SO4 has not
been occurred and this shown that the retention of crystalline
structure of the magnetite. Due to XRD pattern of
2ꢀ
Fe3O4@ZrO2/SO4 can be shown that, the major form of this
catalyst is a tetragonal phase after calcinations.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 3 of 11
Journal Name
RSC Advances
View Article Online
ARTICLE
DOI: 10.1039/C5RA13173A
2
Figure 6: TEM image of Fe3O4@ZrO2/SO4
2ꢀ
Finally, to confirm the structure of Fe3O4@ZrO2/SO4 EDX
spectrum was used. As shown in figure 7, can be cofrimed
existence of iron, oxygen, and sulfur zirconium in the sample of
this catalyst.
2-
Figure 3: SEM of Fe3O4@ZrO2/SO4
Figure 4: The graphs of Fe3O4@ZrO2/SO42- by using Excel software
2-
Figure 7: Energy dispersive X-ray spectroscopy of Fe3O4@ZrO2/SO4
According to result of the analysis VSM, the saturation
magnetizatino curve depicted in Fig. 5 there is not any
hysteresis in the magnetization sweep. Therefore, the magnetic
coercivity of the nano structure is zero, which suggests that the
sample containing Fe3O4 is superparamagnetic.
Figure 5: A) VSM of Fe3O4@ZrO2/SO42-, synthesized by 0.3 gr Fe3O4 and calcinated
in at air atmosphere.B) VSM of Fe3O4@ZrO2/SO42-, synthesized by 3 gr Fe3O4 and
calcinated in Nitrogen furnace .
Figure 8: Nitrogen adsorption- desorption isotherm and pore- size distribution of
2-
Fe3O4@ZrO2/SO4
.
TEM in figure 6 has shown quantitative measures of particle
and grain size, size distribution, and morphology.
N2 adsorption measurements were measured to investigate the
BET specific surface area of the Fe3O4@ZrO2/SO42ꢀ. As can be
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 3

RSC Advances
Page 4 of 11
ARTICLE
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5RA13173A
2ꢀ
seen from figure 8, the BET surface area of Fe3O4@ZrO2/SO4
is 121 m2/g. The high specific surface may endow the material
stronger catalytic properties. The corresponding poreꢀ size
distribution determined by BJH method are also shown in
figure 8 (3.77 nm).
Table1.The various conditions for the KabachnikꢀFields reaction in the
presence of a Fe3O4@ZrO2/SO42ꢀ catalyst (a)
.
Time Catalyst Yield
Entry
Solvent
Temperature
(min)
(mg)
(%)b
(oC)
80
1
2
3
4
5
6
7
8
9
EtOH
H2O
CH3CN
20
20
20
20
20
20
20
20
20
20
80
80
80
80
80
80
80
60
40
100
65
low
65
93
10
65
93
75
73
95
Catalytic properties
80
80
80
RT
60
100
80
80
-
-
-
-
-
-
-
The proposed mechanism of the KabachnikꢀFields reaction in
the presence of a Fe3O4@ZrO2/SO42ꢀ catalyst
The
proposed
mechanism
for
the
synthesis
of
2ꢀ
αꢀaminophosphonate with the Fe3O4@ZrO2/SO4 catalyst has
been shown in scheme 2. According to this mechanism, catalyst
can be facilated the formation of imine intermediate by
activating the carbonyl group. 39
10
80
a
Reaction conditions: 2ꢀchlorobenzaldehyde (1.0 mmol), aniline (1.0mmol),
dimethyl phosphite (1.2 eq), catalyst (aldehyde or ketone was added with
O
P
catalyst), solvent (2.0 ml). b Isolated yields.
MeO
OMe
H
ꢀ H2O
O
R2
R1
R1
R2
N
P
R
After obtaining the optimized conditions, the reaction for the
preparation of αꢀaminophosphonate was carried out in solvent
free and 80°C. In the first step,the reaction were studied
without catalyst and then with the iron oxide magnetic
nanoparticles, oxide nanoparticles zirconium and zirconium
(IV) chloride as a catalyst of this reaction. The results in table 2
(4ꢀ7) are summarized.
HO
OMe
OMe
O
R1
R2
R
NH2
MeO
P
O H
MeO
R1
R2
N
OMe
R
OMe
O
P
H
R2
N
R
R1
Table 2 various conditions for the preparation of αꢀaminophosphonat
e
with and without catalysts (a)
.
2ꢀ
Catalyst (Fe3O4@ZrO2/SO4
)
=
Catalyst
(mol %)
-
10
10
10
80 (mg)
80 (mg)
80 (mg)
Time
(min)
24(hr)
20
20
20
20
20
20
Yield
(%)b
Scheme 2. The proposed mechanism of the Kabachnik-Fields reaction in the
presence of a Fe3O4@ZrO2/SO42- catalyst
Entry
Catalyst
1
2
3
4
5
6
7
30
76
82
85
45
36
93
-
NanoꢀFe3O4
NanoꢀZrO2
ZrCl4
ZrO2/SO4
Fe3O4@ZrO2
In the presence of catalyst, carbon of imine attacked by
phospite and the desired product is obtained.
2ꢀ
The optimal conditions for the KabachnikꢀFields reaction in the
presence of a Fe3O4@ZrO2/SO42ꢀ catalyst
2ꢀ
Fe3O4@ZrO2/SO4
In the first, reaction done in ethanol, 80°C temperature and in
the presence of 80 mg of catalyst and production was obtained
in the yield of 65%. To improve the efficiency of the reaction,
the effect of different solvents such as water, acetonitrile and
solventꢀfree conditions were studied and the best yields were
obtained in solventꢀfree conditions. The effect of temperature
on the reaction efficiency was investigated. Therefore, the
optimal conditions were obtained: 80 mg of the catalyst,
temperature of 80°C with solvent free condition (table 1).
a
Reaction conditions: 2ꢀchlorobenzaldehyde (1.0 mmol), aniline (1.0mmol),
dimethyl phosphite (1.2 eq), catalyst, solventꢀfree, 80 0C .b Isolated yields.
In the absence of a catalyst, the reaction did not progress. Nano
magnetic sulfated zirconia catalyst (Fe3O4@ZrO2/SO42ꢀ) in
comparison with other catalysts has a higher yield. It was
observed that the addition of Fe3O4 to sulfated zirconia
dramatically affected the catalytic activity in the synthesis of
α−aminophosphonates (entries 5, 7, Table 2), it was found that
iron oxide (Fe3O4) modifies the sulfated zirconia surface by
generating acidic sites of medium strength. Sufficiently doping
the sulfated zirconia with iron oxide can increase the total
number acidic sites with lower strength. These changes,
especially the simultaneous presence of two acidic type sites
with different strengths, are interesting for catalytic activity.
The ionic nature of S=O imparts the Bronsted acid site to the
catalyst which enhances the acidity of the material thereby
reinforcing the catalytic activity (entries 6, 7, Table 2).
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 5 of 11
Journal Name
RSC Advances
View Article Online
ARTICLE
DOI: 10.1039/C5RA13173A
The optimal conditions for the development of other derivatives
of αꢀaminophosphonates
using a XꢀPERTꢀ PRO diffractometer with Cu Kα, (λ= 1.54 Å)
irradiation, in the range of 5 to 80 (2θ) with a scan Step of
0.026. The morphology of catalyst was studied with scanning
electron microscopy using SEM (KYKY, EM 3200) on gold
This reaction performed with simple and sensitive aldehydes to
acid such as thiophene carbaldehyde and also several amines
and the products were obtained with good yields. In addition to
aldehydes, ketones were also tested. For example,
cyclohexanone can be react with aniline and dimethyl
phosphate and the product was obtained in good yield. All the
derivatives has been shown in table 4.
2ꢀ
coated samples. The magnetic properties of Fe3O4@ZrO2/SO4
nanoparticles were measured with a vibrating magnetometer/
Alternating Gradient Force Magnetometer (VSM/, MDKFD).
2ꢀ
The BET surface area and pore volume of Fe3O4@ZrO2/SO4
was determined with a micromeritics ASAP 2020 apparatus
using nitrogen as the analysis gas.
Recyclability of the Fe3O4@ZrO2/SO42ꢀcatalyst in Kabachnikꢀ
Fields reaction
Preparation of the magnetic Fe3O4 nanoparticles (MNPs)
Reusability of catalyst for the reaction between 2ꢀchloro
benzaldehyde, aniline and dimethyl Phosphite was investigated.
When the reaction was completed, catalyst separated with an
external magnetic field and then was washed with ethanol and
dried at room temperature and subsequent reactions without
further purification was followed. The catalyst recycled and
used 5 times in a row without a significant change in the
catalytic capability (figure 9).
Ferric acid and ferrous salts were employed as precursors for
the synthesis of Fe3O4 nano particles. Briefly, FeCl3.6H2O (12.2
g, 0.04 mol) and FeCl2.4H2O (4.7 g, 0.02 mol) were dissolved
in 100 ml distilled water under vigorous stirring. After 10
minutes, the solution was heated at 50 0C under nitrogen
atmosphere. Consequently, the ammonium hydroxide solution
(25%) was added dropwise to the reaction mixture to maintain
the reaction pH about 9. Afterward, the reaction mixture was
cooled at room temperature and black precipitate which was
separated by external magnet from the reaction mixture,
repeatedly washed with deꢀionized water for several times to
remove the remaining impurities. At the final step nanoparticles
was dried at 60 0C in vacue.
2ꢀ
General procedure for the synthesis of Fe3O4@ZrO2/SO4
Initially 30g ZrCl4 were dissolved in 1000 ml EtOH: H2O (1:1)
to form a colorless solution and aqueous ammonia (10%) was
added dropwise under vigorous stirring until the pH of the
solution reached 2. Then 3g Fe3O4NPs was added to the
mixture, after that aqueous ammonia (10%) was added
dropwise again under sonication up to pH 9. The precipitate
was filtered, thoroughly washed with distilled water, the
absence of chloride ion was confirmed by AgNO3 test.
Subsequently the obtained solid was dipped in (NH4)2SO4 (3
mol.Lꢀ1) aqueous solution at room temperature for 24 h. Then
the solid was filtered, dried without washing overnight at 100
0C and calcined at 600 0C, for 6 h in the N2 atmosphere.
2-
Figure 9: Recyclability of the Fe3O4@ZrO2/SO4 catalyst in Kabachnik-Fields
reaction
Comparison of the results obtained in the the synthesis of αꢀ
2ꢀ
aminophosphonat in the presence of Fe3O4@ZrO2/SO4
catalyst and other catalysts which have been reported
Finally, a comparative study of the catalytic system with some
recent reported in oneꢀpot reaction between benzaldehyde,
aniline and dimethyl phosphite indicates that, the catalytic
propertise of Fe3O4@ZrO2/SO4 is comparable with other
catalytic reported systems (table 3).
General procedure for the synthesis of αꢀaminophosphonates
To a mixture of aldehydes or ketones (1 mmol), amine (1
mmol) and dimethylphosphite (1.2 mmol) in the percense of
2ꢀ
2ꢀ
Fe3O4@ZrO2/SO4 (80.0 mg) and stirred at 80oC for the
appropriate reaction time (for the period of time listed in Table
4), The reaction was monitored by TLC (50:50 EtOAC/nꢀ
hexane), Dichloromethane was added after completion of the
reaction, catalyst was recovered with an external magnet (or
filteration). A saturated aqueous NaHCO3 solution (20 mL) and
brine (20 mL) were added, the mixture was extracted with
EtOAc (25 mL), and the organic layer was dried over
anhydrous Na2SO4. The solvent was evaporated under reduced
pressure, and the crude product was purified either by
recrystallization or by preparative TLC (silica gel) (eluent:
50:50 EtOAC/nꢀhexane) if necessary. The products thus
obtained(in table4) were characterized by mp, IR, NMR
Experimental
Chemicals and Instruments
All chemicals used, such as salts of iron (III) chloride, iron (II)
chloride, zirconium (IV) chloride, ammonium sulfate,
aldehydes, ketones, amines, and dimethyl phosphite and
solvents used were supplied by Merck and Aldrich chemical
companies. FTꢀIR spectra were obtained over the region 400ꢀ
4000 cmꢀ1 with a Nicolet IR 100 FTꢀIR with spectroscopic
grade KBr. The powder Xꢀray diffraction pattern was recorded
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5

RSC Advances
Page 6 of 11
VJieowuArrtnicalelONnlainme e
ARTICLE
DOI: 10.1039/C5RA13173A
spectroscopy; Spectral data for selected products is presented in The end point was reached when the colour changed from pink
the support information.
to colourless.
2ꢀ
Spectral data : reported in the support information.
Back titration in aqueous media catalyst Fe3O4@ZrO2/SO4
The amount of released [H+] by catalyst was determined by
back titration. In a container which contained 35 ml of distilled
water, 0.5 g of NaCl, 0.5 g catalyst and 10 ml NaOH (0.1 M)
were added and stirred for 24 h on a magnetic stirrer until
neutralized [H+] which produced from catalyst hydrolysis. Then
three drops of phenolphthalein were added to the container and
the solution titrated with 0.1 M solution of hydrochloric acid.
Table 3: Comparison of the results obtained in the the synthesis of αꢀaminophosphonate in the presence of Fe3O4@ZrO2/SO42ꢀ catalyst and other
catalysts
temp
(oC)
catalyst
(mol %)
Time
(hr)
Yield
(%)
Entry
Solvent
Ref.
Cat 1
(5)
1
2
3
4
5
CH3CN
3
2
2
2
rt
90
98
94
93
95
26
Cat 2
(10)
-
-
-
-
50
35
40
80
39
Cat 3
(10)
35
36
Cat 4
(0.09)
Cat 5
(80 mg)
30
(min)
Present work
2ꢀ
Catalysts: 1ꢀ SbCl3/Al2O3, 2ꢀ Oxalic acid, 3ꢀ MgFe2O4, 4ꢀ DHAA@Fe3O4, 5ꢀ Fe3O4@ZrO2/SO4
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 7 of 11
Journal Name
RSC Advances
View ArticAle ROnTliInCeLE
DOI: 10.1039/C5RA13173A
2ꢀa
Table 4. synthesis derivatives of αꢀaminophosphonate in the presence catalyst Fe3O4@ZrO2/SO4
Time
Yield
(%)b
Entry
1
Carbonyls
PhCHO
amines
Aniline
Products
Mp(oC)[Ref]
(min)
30
O
P
OMe
OMe
90ꢀ92
[41]
95
93
95
NHPh
1a
1b
Cl
O
OMe
OMe
128ꢀ129
[42]
P
2
3
20
15
2ꢀ(Cl)C6H4CHO
4ꢀ(Cl)C6H4CHO
Aniline
Aniline
NHPh
Cl
O
P
OMe
OMe
139ꢀ140
[43]
NHPh
1c
Cl
Cl
O
OMe
OMe
P
110ꢀ112
[42]
4
5
30
70
2,4ꢀ(Cl)2C6H3CHO
2,6ꢀ(Cl)2C6H3CHO
Aniline
Aniline
89
85
NHPh
1d
Cl
O
P
OMe
OMe
98ꢀ100
[19]
Cl
NHPh
1e
Me
O
OMe
OMe
P
125ꢀ128
[45]
6
25
4ꢀ(Me)C6H4CHO
Aniline
93
NHPh
1f
MeO
O
P
OMe
OMe
123ꢀ124
[41]
7
8
15
20
4ꢀ(OMe)C6H4CHO
4ꢀ(NO2)C6H4CHO
Aniline
Aniline
90
96
NHPh
O
1g
O2N
OMe
P
127ꢀ128
[41]
OMe
NHPh
1h
NO2
OH
O
122ꢀ124
[44]
OMe
OMe
9
40
3ꢀ(NO2)C6H4CHO
Aniline
95
P
NHPh
1i
O
P
OMe
OMe
130ꢀ132
Present work
10
11
12
20
80
30
3ꢀ(OH) C6H4CHO
Thiophenꢀ2ꢀcarbaldehyde
1ꢀnaphthaldehyde
Aniline
Aniline
Aniline
96
80
90
NHPh
1j
O
OMe
P
83ꢀ86
[19]
OMe
S
NHPh
1k
143ꢀ145
[45]
OMe
OMe
PhHN
P
O
1l
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 7

RSC Advances
Page 8 of 11
ARTICLE
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5RA13173A
Me
N
Me
O
P
OMe
OMe
4ꢀ(dimethyl amino)
benzaldehyde
144
[13]
13
20
Aniline
85
NHPh
1m
NHPh
O
P
O
OMe
170ꢀ173
[46]
14c
15
15
10
Terephthaldehyde
4ꢀ(NO2)C6H4CHO
Aniline
90
92
MeO
P
MeO
MeO
NHPh
1n
Me
Me
HN
209ꢀ211
[47, 52]
p-Toluidine
O
P
OMe
MeO
1oO N
2
HN
96ꢀ99
[41]
O
16
20
4ꢀ(OMe)C6H4CHO
p-Toluidine
88
P
OMe
MeO
MeO
1p
NO2
HN
160ꢀ162
[13]
O
17
18
15
25
4ꢀ(Cl)C6H4CHO
4ꢀNitroaniline
4ꢀNitroaniline
76
82
P
OMe
MeO
Cl
1q
NO2
HN
150ꢀ152
[13]
O
4ꢀ(OMe)C6H4CHO
P
OMe
MeO
MeO
1r
NO2
HN
170ꢀ173
[13]
O
19
15
4ꢀ(NO2)C6H4CHO
4ꢀNitroaniline
80
P
OMe
MeO
O2N
1s
1t
O
P
99ꢀ102
[13]
OMe
OMe
20
21
50
Cyclohexanone
Acetophenone
Aniline
Aniline
75
70
NHPh
NHPh
P
OMe
OMe
125ꢀ129
[13]
120
O
1u
a Reaction conditions: aldehyde or ketone (1.0 mmol), amine (1.0 mmol), dimethyl phosphite (1.2 eq), catalyst (80 mg), under solventꢀfree condition, 80oC, b
Isolated yield, c Reaction condition: aldehyde (1.0 mmol), amine (2.0 mmol), dimethyl phosphite (2.4 eq), catalyst (100 mg) , solventꢀfree, 80oC.
loss of activity, short reaction time, high yielid, and easy work
Conclusion
2
up processe. Thermal durability of Fe3O4@ZrO2/SO4 ꢀ and good
There are many routes to synthesized αꢀaminophosphonate
derivatives.49ꢀ51 In this work we introduced sulfated zirconia
supported on magnetic nanoparticles as an effective
nanocatalyst for KabachnikꢀFields reaction to synthesis of
αꢀaminophosphonate derivatives. From the best advantages of
resistance of fanctional groups in washing process are two
briliant benefits of this compund as a catalyst in reactions.
2
Fe3O4@ZrO2/SO4 ꢀ as a nanocatalyst are easy separation by the
external magnetic field and recyclability of catalyst without
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 9 of 11
Journal Name
RSC Advances
View ArticAle ROnTliInCeLE
DOI: 10.1039/C5RA13173A
25ꢀ D. Mahajan, B.A. Ganai, R.L. Sharma and K.K. Kapoor, Tetrahedron
letters, 2006, 47, 7919ꢀ7921.
Acknowledgments
The authors gratefully acknowledge the partial support from the
Research Council of the Iran University of Science and
Technology.
26ꢀ S. Kumar, S.C. Taneja, M.S. Hundal and K.K. Kapoor, Tetrahedron
Letters, 2008, 49, 2208ꢀ2212.
27ꢀ B. Kaboudin and R. Nazari, Tetrahedron Letters, 2001, 42, 8211ꢀ
8213.
Notes and references
28ꢀ A.K. Bhattacharya and K.C. Rana, Tetrahedron Letters, 2008, 49
,
aDepartment of Chemistry of Iran University of Science and Technology,
Tehran, Iran. 16846_13114, Fax: 982177491204; Tel: 982177240516-7, E-
mail: ghafuri@iust.ac.ir
2598ꢀ2601.
29ꢀ M. Timofeeva, Applied Catalysis A: General, 2003, 256, 19ꢀ35.
30ꢀ A. Heydari, H. Hamadi and M. Pourayoubi, Catalysis
Communications, 2007, , 1224ꢀ1226.
8
References
31ꢀ B. Kaboudin and E. Jafari, Synlett, 2008, 1837ꢀ1839.
32ꢀ S. Bhagat and A.K. Chakraborti, The Journal of organic chemistry
2008, 73, 6029ꢀ6032.
,
,
1ꢀ D.E.C. Corbridge, Phosphorusꢀan outline ofits chemistry, biochemistry
and technology, Elsevier Science Publishers BV, 1985.
2ꢀ R. Hudson, Organo-Phosphorus Chemistry, 1965, 24ꢀ28.
3ꢀ S. Chandrasekhar, S.J. Prakash, V. Jagadeshwar and C. Narsihmulu,
Tetrahedron Letters, 2001, 42, 5561ꢀ5563.
33ꢀ S. Kudrimoti and V. Rao Bommena, Tetrahedron letters, 2005, 46
1209ꢀ1210.
34ꢀ S. Mitragotri and D. Pore, U. Desai, P. Wadgaonkar, Catalysis
Communications, 2008, , 1822ꢀ1826.
9
4ꢀ N. Azizi and M.R. Saidi, Tetrahedron, 2003, 59, 5329ꢀ5332.
5ꢀ J. Genet, J. Uziel, M. Port, A. Touzin, S. Roland, S. Thorimbert and S.
Tanier, Tetrahedron letters, 1992, 33, 77ꢀ80.
35ꢀ M. Sheykhan, H. Mohammadnejad, J. Akbari and A. Heydari,
Tetrahedron Letters, 2012, 53, 2959ꢀ2964.
36ꢀ D. Saberi, S. Cheraghi, S. Mahdudi, J. Akbari and A. Heydari,
Tetrahedron Letters, 2013, 54, 6403ꢀ6406.
6ꢀ A. Pudovik, Dokl Akad Nauk SSSR, 1952, 865ꢀ868.
7ꢀ A. Heydari, A. Karimian and J. Ipaktschi, Tetrahedron letters, 1998,
39, 6729ꢀ6732.
37ꢀ Wu, J; Sun, W; Xiaa, H and Suna, X. Org. Biomol. Chem., 2006, 4,
1663ꢀ1666.
8ꢀ N. Azizi and M.R. Saidi, European Journal of Organic Chemistry
2003, 23, 4630ꢀ4633.
,
38ꢀ H. Ghafuri and M. Roshani. Rsc adv. 2014, 4, 58280ꢀ58286.
39ꢀ H. Ghafuri, A. Rashidizadeh, B. Ghorbani and M. Talebi, New
Journal of Chemistry, 2015, 39, 4821ꢀ4829.
9ꢀ B.C. Ranu and A. Hajra, U. Jana, Organic Letters, 1999, 1, 1141ꢀ1143.
10ꢀ K. Manabe and S. Kobayashi, Chemical Communications, 2000,
669ꢀ670.
8,
40ꢀ S.M. Vahdat, R. Baharfar, M. Tajbakhsh, A. Heydari, S.M.
Baghbanian, S. Khaksar, Tetrahedron Letters, 2008, 49, 6501ꢀ6504.
11ꢀ B. Kaboudin and A. Rahmani, Synthesis, 2003, 17, 2705ꢀ2708.
41ꢀ X.ꢀJ. Mu, M.ꢀY. Lei, J.ꢀP. Zou and W. Zhang, Tetrahedron letters
,
12ꢀ T. Akiyama, M. Sanada and K. Fuchibe, Synlett, 2003, 10, 1463ꢀ
2006, 47, 1125ꢀ1127.
1464.
42ꢀ M.T. Maghsoodlou, S.M.H. Khorassani, N. Hazeri, M. 2, S.S.
13ꢀ S. Bhagat and A.K. Chakraborti, The Journal of organic chemistry
2007, 72, 1263ꢀ1270.
,
Sajadikhah, Z. Shahkarami and N. Maleki, Heteroatom Chemistry
2009, 20, 316ꢀ318.
,
14ꢀ Y.T. Reddy, P.N. Reddy, B.S. Kumar, P. Rajput, N. Sreenivasulu and
B. Rajitha, Phosphorus, Sulfur and Silicon, 2007, 182, 161ꢀ165.
43ꢀ L. Lukanov and A. Venkov, Synthesis, 1992, 3, 263ꢀ264.
,
44ꢀ A. Pudovik and M. Ikorchemkina, Izvestiya akademii NAUK SSSR-
Seriya Khimicheskaya, 1952, 940ꢀ946.
15ꢀ A. Heydari and A. Arefi, Catalysis Communications, 2007, 8, 1023ꢀ
1026.
45ꢀ B. Movassagh and S. Alapour, Heteroatom Chemistry, 2013, 24, 174ꢀ
178.
16ꢀ K.M. Yager, C.M. Taylor and A.B. Smith, Journal of the American
Chemical Society, 1994, 116, 9377ꢀ9378.
46ꢀ A. Pudovik and M. Pudovik, journal of general chemistry USSR
1996, 36, 1471.
,
17ꢀ D. Simoni, F.P. Invidiata, M. Manferdini, I. Lampronti, R. Rondanin,
M. Roberti and G.P .Pollini, Tetrahedron letters, 1998, 39, 7615ꢀ
7618.
47ꢀ X. Zhang, Y. Qu, X. Fan, C. Bores, D. Feng, G. Andrei, R. Snoeck,
E. De Clercq and P.M. Loiseau, Nucleosides, Nucleotides and
Nucleic Acids, 2010, 29, 616.
18ꢀ A. Klepacz and A. Zwierzak, Tetrahedron letters, 2002, 43, 1079ꢀ
1080.
48ꢀ D. V. Vorobyeva, N. M. Karimova, I. L. Odinets, G. Röschenthaler
19ꢀ A. Manjula, B. Vittal Rao and P. Neelakantan, Synthetic
communications, 2003, 33, 2963ꢀ2969.
and S. N. Osipova, Org. Biomol. Chem., 2011, 9, 7335ꢀ7342.
49ꢀ F. Palacios, T. K. Olszewskia and J. Vicarioa, Org. Biomol. Chem.
2010, 8, 4255ꢀ4258.
,
20ꢀ S. Doye, Synlett, 2004, 1653ꢀ1672.
21ꢀ I. Schlemminger, A. Willecke, W. Maison, R. Koch, A. Lützen and J.
50ꢀ L. Gu and Ch. Jin, Org. Biomol. Chem., 2012, 10, 7098ꢀ7102.
Martens, J. Chem. Soc., Perkin Trans., 2001,
1, 2804ꢀ2816.
22ꢀ S. Laschat and H. Kunz, Synthesis, 1992, , 90ꢀ95.
1
23ꢀ E. Matveeva and N. Zefirov, Russian journal of organic chemistry
2006, 42, 1237ꢀ1238.
,
51ꢀ B. Srikant, S. Parth, K.G Sanjeev, M. Shweta , K.K. Preet, S. Sushma,
C.K. Asit , Med. Chem. Commun., 2014, 5, 665ꢀ670.
24ꢀ Z. Hou, N. Theyssen and W. Leitner, Green Chemistry, 2007, 9, 127ꢀ
52ꢀY. Yu, D. Zhen Xu, Synthesis, 2015, 47, 1869ꢀ1876.
132.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 9

RSC Advances
Page 10 of 11
ARTICLE
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5RA13173A
53ꢀ Shafeek A. R. Mulla, Mohsinkhan Y. Pathan, Santosh S. Chavan, Suwara
P. Gample, Dhiman Sarkar, RSC Adv., 2014, 4,7666ꢀ7672.
10 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 11 of 11
RSC Advances
View Article Online
DOI: 10.1039/C5RA13173A
Highly efficient solvent free synthesis of α-aminophosphonates
catalyzed by recyclable nano magnetic sulfated zirconia
2-
(Fe3O4@ZrO2/SO4 )
Hossein Ghafuri,*aAfsaneh Rashidizadeha and Hamid Reza Esmaili Zanda
aDepartment of Chemistry of Iran University of Science and Technology, Tehran, Iran. 16846_13114, Fax: 982177491204; Tel: 982177240516-
7, E-mail: ghafuri@iust.ac.ir