Nano-TiO 2: An eco-friendly and clean reusable heterogeneous catalyst for preparation of α-aminophosphonates under ambient and solvent-free conditions

Article abstract of DOI:10.1080/10426507.2012.717135

A one-pot catalytic three-component synthesis of α-aminophosphonates from arylaldehydes, anilines, and triethylphosphite by employing TiO₂ nanoparticles as a catalyst is described. Nano-TiO₂ has been found to be an excellent catalyst for the green synthesis of α-aminophosphonates under ambient and solvent-free conditions. This green and mild nano catalytic procedure showed good recyclability and provides cleaner conversion in a short reaction time. These advantages make the protocol feasible and economically attractive for researchers.

Full text of DOI:10.1080/10426507.2012.717135

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Phosphorus, Sulfur, and Silicon and the
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Nano-TiO2: An Eco-Friendly and Clean
Reusable Heterogeneous Catalyst for
Preparation of α-Aminophosphonates
Under Ambient and Solvent-Free
Conditions
Hamid Reza Shaterian a , Javad Farbodeh a & Majid Mohammadnia a
a Department of Chemistry, Faculty of Sciences , University of Sistan
and Baluchestan , Zahedan , Iran
Accepted author version posted online: 09 Aug 2012.Published
online: 05 Jul 2013.
To cite this article: Hamid Reza Shaterian , Javad Farbodeh & Majid Mohammadnia (2013) Nano-TiO2:
An Eco-Friendly and Clean Reusable Heterogeneous Catalyst for Preparation of α-Aminophosphonates
Under Ambient and Solvent-Free Conditions, Phosphorus, Sulfur, and Silicon and the Related
Elements, 188:7, 850-854, DOI: 10.1080/10426507.2012.717135
To link to this article: http://dx.doi.org/10.1080/10426507.2012.717135
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Phosphorus, Sulfur, and Silicon, 188:850–854, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.717135
NANO-TiO2: AN ECO-FRIENDLY AND CLEAN REUSABLE
HETEROGENEOUS CATALYST FOR PREPARATION
OF α-AMINOPHOSPHONATES UNDER AMBIENT
AND SOLVENT-FREE CONDITIONS
Hamid Reza Shaterian, Javad Farbodeh,
and Majid Mohammadnia
Department of Chemistry, Faculty of Sciences, University of Sistan and
Baluchestan, Zahedan, Iran
GRAPHICAL ABSTRACT
Abstract A one-pot catalytic three-component synthesis of α-aminophosphonates from ary-
laldehydes, anilines, and triethylphosphite by employing TiO2 nanoparticles as a catalyst is
described. Nano-TiO2 has been found to be an excellent catalyst for the green synthesis of
α-aminophosphonates under ambient and solvent-free conditions. This green and mild nano
catalytic procedure showed good recyclability and provides cleaner conversion in a short
reaction time. These advantages make the protocol feasible and economically attractive for
researchers.
Keywords Nano-TiO2; three-component reaction; α-aminophosphonates; catalyst; solvent-
free; ambient conditions
INTRODUCTION
Phosphonic acids and their phosphonate derivatives are of immense interest
in synthetic organic chemistry due to their biological activities.1 The synthesis of
α-aminophosphonates has attracted much interest because of their biological activity
and structural analogy to α-amino acids as well as heterocyclic phosphonates.2 Their
diverse applications include inhibition of synthase,3 HIV protease,4 renin,5 and PTPases,6,7
Received 10 May 2012; accepted 14 July 2012.
We are thankful to the University of Sistan and Baluchestan Research Council for the partial support of this
research.
Address correspondence to Hamid Reza Shaterian, Department of Chemistry, Faculty of Sciences, University
of Sistan and Baluchestan, PO Box 98135-674, Zahedan Iran. E-mail: hrshaterian@chem.usb.ac.ir
850

NANO-TIO2 AND α-AMINOPHOSPHONATES
851
some of these derivatives are potential antibiotics8 or herbicides.9 Furthermore,
α-aminophosphonates are chief substrates in the synthesis of phosphonopeptides.10
Nanoparticles are of great scientific interest as they are effectively a bridge between
bulk materials and atomic or molecular structures. A bulk material should have constant
physical properties regardless of its size, but at the nanoscale, size-dependent properties
are often observed. Thus, the properties of materials change as their size approaches the
nanoscale and as the percentage of atoms at the surface of a material becomes significant.11,12
Original research on synthetic approach to α-aminophosphonates is the
Kabachnik–Fields reaction.13,14 A number of synthetic methods for the preparation
of α-aminophosphonates have been developed using various Brønsted acids, Lewis
acids, heteropoly acids, heterogeneous catalysts, ionic liquids, and nano catalysts such as
silica-supported boron trifluoride (BF3-SiO2),15 N,N,N-trimethyl-N-propanesulfonic acid
ammonium hydrogensulfate [TMPSA][HSO4],16 choline chloride·2ZnCl2 ionic liquid,17
cadmium perchlorate hydrate,18 cerium(III) chloride heptahydrate CeCl3·7H2O,19 ethyl
ammonium nitrate [EtNH3]NO3,20 1-hexanesulphonic acid sodium salt,21 tetramethyl-
tetra-3,4-pyridinoporphyrazinato copper (II) methyl sulfate [Cu(3,4-tmtppa)](MeSO4)4,22
thiamine hydrochloride (VB1),23 nano-Fe3O4,24 nano-CeO2,25 and commercial bulk
TiO2.26 However, many of these catalysts involve tedious separation procedures21,23 with
prolonged reaction times.22,24 Therefore, the development of a simple, convenient, and an
efficient protocol would extend the scope of the synthesis of α-aminophosphonates.
In this article, we report that nano-TiO2 (10 mol%) is a highly efficient catalyst for the
one-pot three-component coupling synthesis of α-aminophosphonates from arylaldehydes,
anilines, and triethylphosphite under ambient and solvent-free conditions (see Scheme 1).
Scheme 1 Nano-TiO2 catalyzed three-component synthesis of α-aminophosphonates.
RESULTS AND DISCUSSION
In order to optimize the reaction conditions, the reaction between benzaldehyde
(1 mmol), aniline (1 mmol), and triethylphosphite (1 mmol) was chosen as a model.
Initially, we tried to optimize the amount of nano-TiO2 in the reaction model. Thus 0.008 g
(10 mol%), 0.020 g (25 mol%), and 0.035 g (43 mol%) of nano-TiO2 (size < 3 nm) were
used (see Table 1). We found that the amount of nano-TiO2 0.008 g (10 mol%) was the most
effective in catalyzing preparation of α-aminophosphonates under ambient conditions.
Then, to establish the generality, the reaction of several substituted arylaldehydes,
anilines, and triethylphosphite using nano-TiO2 as a catalyst under solvent-free and ambient
conditions were examined. The results are shown in Table 2. We have carried out the

852
H. R. SHATERIAN ET AL.
Table 1 Optimization of the amount of nano-TiO2 as a catalyst in the synthesis of
α-aminophosphonates under ambient conditions
Entry
Catalyst (mol%)
Time (min)
Yield (%)a
1
2
3
10
25
43
9
5
2
90
93
92
aYields refer to isolated pure product.
similar reaction with various aromatic aldehydes containing electron donating or electron
withdrawing functional groups at ortho, meta, and para positions, but it did not showed
any remarkable differences in the yields of product and reaction time.
We also investigated the recycling of the nano-TiO2 as the catalyst under solvent-
free conditions using the model reaction of benzaldehyde, aniline, and triethylphosphite
(10 mol%) (see Table 2, Entry 1). After completion of the reaction, the reaction mixture
was diluted with dichloromethane and the catalyst was separated by centrifugation and was
reused for subsequent experiments under similar reaction conditions. The results showed
us that the nano-TiO2 is a stable catalyst and reused several times without significant loss
of its catalytic activity.
In order to show the accessibility of the present work in comparison with several re-
ported results in the literature, we summarized some of the results for the preparation of di-
ethyl phenyl(phenylamino)methylphosphonate from the reaction of benzaldehyde, aniline,
and triethylphosphite (see Table 3). The results show that nano-TiO2 relative to cerium(III)
chloride heptahydrate (CeCl3·7H2O),19 tetramethyl-tetra-3,4-pyridinoporphyrazinato cop-
per (II) methyl sulfate ([Cu(3,4-tmtppa)](MeSO4)4),22 nano-Fe3O4,24 and bulk TiO226 are
the most efficient catalysts with respect to the reaction time and in terms of yields. In
addition, nanosize of TiO2 with high surface area as a catalyst shows high catalytic activity
Table 2 Synthesis of α-aminophosphonate from the reaction of substituted arylaldehydes, anilines, and tri-
ethylphosphite using nano-TiO2 (10 mol%) as a catalyst under solvent-free and ambient conditions
Time
(min)
Yield
(%)a
Found
Literature
Entry
Arylaldehydes
C6H5CHO
C6H5CHO
C6H5CHO
Anilines
C6H5NH2
4-NO2C6H5NH2
4-BrC6H4NH2
4-MeC6H4NH2
4-MeOC6H4NH2
C6H5NH2
mp (◦C)
mp (◦C)Ref
1
2
3
4
5
6
7
8
9
10
11
12
13
14
9
35
12
12
11
23
15
18
20
22
19
20
18
19
90
85
90
93
87
90
85
90
92
92
92
92
94
93
89–90
145–147
123–124
116–118
116
122–123
65–67
110–111
143–144
109-111
75–76
8719
145–14619
12219
C6H5CHO
C6H5CHO
117–11819
11519
4-NO2C6H4CHO
4-MeC6H4CHO
4-MeOC6H4CHO
4-HOC6H4CHO
3-NO2C6H4CHO
4-ClC6H4CHO
2-HOC6H4CHO
3,4-diMeOC6H3CHO
3,4-diMeOC6H3CHO
12019
C6H5NH2
C6H5NH2
66–6719
10819
4-Cl-2-NO2C6H5NH2
4-Cl-2-NO2C6H5NH2
4-Cl-2-NO2C6H5NH2
4-Cl-2-NO2C6H5NH2
C6H5NH2
141–14320
107–11020
75–7620
125–12820
7719
127–128
76–78
108
4-Cl-2-NO2C6H5NH2
105–10720
aYields refer to isolated pure product. The desired known pure products were characterized by comparison of
their physical data (mp, melting points; IR, 1H NMR, and 13C NMR) with those of known compounds.19,20

NANO-TIO2 AND α-AMINOPHOSPHONATES
853
Table 3 Comparing the results of nano-TiO2 with other metallic catalysts such as cerium (III) chloride
heptahydrate (CeCl3·7H2O),19 tetramethyl-tetra-3,4-pyridinoporphyrazinato copper (II) methyl sulfate ([Cu(3,4-
tmtppa)](MeSO4)4),22 nano-Fe3O4,24 and bulk TiO2 in the synthesis diethyl phenyl(phenylamino)methyl-
26
phosphonate
Entry
Catalyst
Conditions
Time
5 h
Yield (%) [Ref]
9519
1
2
CeCl3·7H2O (5 mol%)
Solvent-free, room
temperature
H2O, 80◦C
[Cu(3,4-tmtppa)](MeSO4)4
(160 mol%)
Nano-Fe3O4 (5 mol%)
Bulk TiO2 (20 mol%)
Nano-TiO2 (10 mol%)
30 min
9622
3
4
5
50◦C
48 min
3.5 h
9 min
9424
9826
50◦C
Solvent-free, room
temperature
90 (present work)
aYields refer to isolated pure products and based on the reaction of benzaldehyde, aniline, and triethylphosphite.
relative to commercial bulk TiO2.26 Nano-TiO2 acts with a low catalytic amount under
ambient and solvent-free conditions, whereas micron-size bulk TiO2 acts with 20 mol%
under thermal conditions.26
CONCLUSIONS
In summary, we have developed a novel efficient solvent-free protocol for the synthe-
sis of α-aminophosphonates using catalytic TiO2 nanoparticle. The method is effective and
provides excellent yields of the products in short reaction time, which makes this protocol a
novel, environmentally friendly, and economically valuable process for the synthesis of this
class of compounds. The nano-TiO2 as a catalyst exhibits a straightforward approach to be
used in green organic synthesis. Nano-TiO2 shows high activity (like a homogeneous and
a heterogeneous system) in spite of micron-size bulk TiO2 (like a heterogeneous system).
EXPERIMENTAL
All reagents were purchased from Merck and Sigma-Aldrich and used without further
purification. Nanopowder TiO2 with a size of ellipsoid <3 nm was purchased from Merck
chemical company (95% anatase, 5% brokite); CAS no: 1317-70-0. All yields refer to
isolated products after purification. Products were characterized by the comparison of
physical data with authentic samples and spectroscopic data (IR and NMR). The NMR
spectra were recorded on a Bruker Avance DPX 500 MHz instrument. The spectra were
measured in CDCl3 relative to TMS (0.00 ppm). IR spectra were recorded on a JASCO
FT-IR 460 plus spectrophotometer. Melting points were determined in open capillaries with
a BUCHI 510 melting point apparatus. Thin layer chromatography (TLC) was performed
on silica-gel polygram SILG/UV 254 plates.
General Procedure for the Preparation of α-aminophosphonates
Arylaldehydes (1 mmol), anilines (1 mmol), triethylphosphite (1 mmol), and nano-
TiO2 (10 mol%, 0.008 g) were mixed under solvent-free and ambient conditions. The
reaction mixture was stirred at room temperature for appropriate time (see Table 2). The

854
H. R. SHATERIAN ET AL.
completion of the reaction was monitored by TLC. After the completion of the reaction,
dichloromethane was added to the reaction mixture and the catalyst was removed from the
reaction mixture by centrifugation, washed with dichloromethane, and dried. The reusable
nano catalyst clearly reveals that the nano-TiO2 can be used for four cycles without any
significant loss in its activity. The organic solvent was removed under reduced pressure.
After purification by column chromatography on silica gel (ethyl acetate/n-hexane 20:80 as
eluent), the α-aminophosphonates were obtained. All products were characterized by NMR
and FTIR spectral data and compared with the known compounds in the literature.19,20
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