Silica supported polyphosphoric acid (PPA-SiO2): An efficient and reusable heterogeneous catalyst for the one-pot synthesis of α-amino phosphonates

Article abstract of DOI:10.3906/kim-0910-28

An efficient green protocol is described for the preparation of α-amino phosphonates, employing a one-pot three-component condensation reaction between aldehydes, amines, and trialkyl phosphites in the presence of PPA-SiO₂ under solvent-free conditions at 80 ° C. The present procedure offer advantages such as high to excellent yields, short reaction time, inexpensiveness, recovery, and reusability of catalyst. tuebitak.

Full text of DOI:10.3906/kim-0910-28

Turk J Chem
34 (2010) , 565 – 570.
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c
ꢀ TUBITAK
doi:10.3906/kim-0910-28
Silica supported polyphosphoric acid (PPA-SiO2 ): an
efficient and reusable heterogeneous catalyst for the
one-pot synthesis of α-amino phosphonates
Malek Taher MAGHSOODLOU1,∗, Sayyed Mostafa HABIBI KHORASSANI1,
Reza HEYDARI1, Nourollah HAZERI1, Seyed Sajad SAJADIKHAH1,
Mohsen ROSTAMIZADEH1 and Leila KEISHAMS2
1Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan,
P. O. Box 98135-674, Zahedan-IRAN
e-mail: mt maghsoodlou@yahoo.com
2Central Laboratory, Shahid Chamran University, Ahvaz-IRAN
Received 12.10.2009
An efficient green protocol is described for the preparation of α-amino phosphonates, employing a one-pot
three-component condensation reaction between aldehydes, amines, and trialkyl phosphites in the presence
of PPA-SiO2 under solvent-free conditions at 80 ◦ C. The present procedure offer advantages such as high
to excellent yields, short reaction time, inexpensiveness, recovery, and reusability of catalyst.
Key Words: α-Amino phosphonates; PPA-SiO2 ; heterogeneous catalyst; trialkyl phosphites
Introduction
The development of simple synthesis routes for widely used organic compounds using readily available reagents
is one of the most important tasks in organic chemistry.1 Organophosphorus compounds are synthetic reagents
of interest, at least because of their value for a variety of industrial, biological, and chemical synthetic uses.2,3 α-
Amino phosphonates have been reported as enzyme inhibitors,4 HIV protease,5 antibiotics,6 and antimicrobial
agents,7 peptide mimics,8 anti-therombotics,9 herbicides, insecticides, and fungicides.10 As a result, a large
number of methods have appeared describing novel synthesis for α-amino phosphonates by nucleophilic addition
∗Corresponding author
565

Silica supported polyphosphoric acid..., M. T. MAGHSOODLOU, et al.,
reactions between phosphites and imines.13−15 However, these reactions cannot proceed in a one-pot reaction
because the amines and water that exist during imine formation can decompose or deactivate the Lewis acids. 16
To overcome some of these problems, recently one-pot three-component procedures have been devel-
oped. This conversion can proceed using lanthanide triflate,17 InCl3 ,18 scandium tris(dodecyl sulfate),19
TaCl 5 -SiO2 ,20 lithium perchlorate,21 CF3 CO2 H,22 metal triflates [M(OTf)n , M = Li, Mg, Al, Cu, Ce],23
27
In(OTf)3 ,24 magnesium perchlorate,25 PhNMe3 Cl,26 H3 PW12 O40
,
Amberlite-IR 120,28 Amberlyst-15,29
sulfamic acid,30 TiO2 ,31 oxalic acid,32 microwave assisted,33 trifluoroethanol,34 AlCl3 ,35 and (bromodimethyl)
sulfonium bromide.36 However, most of these methods displayed drawbacks such as environmental pollution
caused by utilization of organic solvents, unsatisfactory yields, long reaction times, drastic reaction conditions,
and the help of microwave irradiation. Furthermore, some of these catalysts are either expensive or difficult to
prepare and cannot be recovered.
Recently, heterogeneous catalysts have attracted increasing interest due to economic and environmental
considerations. One of these heterogeneous catalysts is silica supported polyphosphoric acid (PPA-SiO2). PPA-
SiO2 was prepared from the reaction of silica gel with polyphosphoric acid.37 PPA-SiO2 has been explored as
a powerful catalyst for various organic transformations under mild conditions.37−40 Herein we report a novel,
simple, and efficient protocol for a one-pot three-component synthesis of α-amino phosphonates (Figure).
Ar2
H
N
H
N
OR
P
O
PPA-SiO2
O
+
+
Ar1
P
Ar1
Ar2
RO
OR
solvent-free, 80 °C
H
H
OR
RO
Figure. Synthesis of α-amino phosphonates.
Experimental
General procedure for preparation of α-amino phosphonates: The aldehyde (1 mmol), amine (1 mmol), and
PPA-SiO2 (0.05 g, 0.025 mmol H+) were stirred for a few minutes. Then trimethyl/triethyl phosphite (1
mmol) was added. The mixture was stirred at 80 ◦ C in an oil bath for the appropriate time (see Table 2).
After completion of the reaction (followed by TLC), the reaction mixture was cooled and CH2 Cl2 (10 mL) was
added. The catalyst was separated by simple filtration and the filtrate was washed with H2 O (3 × 10 mL).
Then the organic layer dried over anhydrous Na2 SO4 and was evaporated. The crude product was purified
by silica gel column chromatography with the mixture of n-hexane/EtOAc (7:3) as an eluent to provide pure
α-amino phosphonates. Physical and chemical data of the new products are represented below:
Compound 11: White solid, mp 133-135 ◦ C. 1 H-NMR (400 MHz, CDCl3): δ = 2.53 (s, 3H), 3.41 (d, J
= 10.5 Hz, 3H), 3.80 (d, J = 10.5 Hz, 3H), 4.60 (br, 1H), 5.06 (d, J = 23.8 Hz, 1H), 6.58 (d, J = 8.5 Hz, 2H),
6.72 (t, J = 7.3 Hz, 1H), 7.10-7.28 (m, 5H), 7.55 (d, J = 2.7 Hz, 1H) ppm; 13 C-NMR (100 MHz, CDCl3):
δ = 19.68, 51.89 (d, J = 151.2 Hz), 53.72 (d, J = 6.9 Hz), 53.85 (d, J = 6.9 HZ), 113.81, 118.69, 126.64 (d,
J = 2.9 Hz), 127.21 (d, J = 4.5 Hz), 128.96, 129.25, 130.65 (d, J = 2.5 Hz), 133.68, 136.33 (d, J = 6.7 Hz),
145.79 (d, J = 14.4 Hz) ppm; 31 P-NMR (161 MHz, CDCl3): δ = 25.86 ppm; IR (KBr, cm−1): 3314 (NH),
566

Silica supported polyphosphoric acid..., M. T. MAGHSOODLOU, et al.,
1234 (P=O),1060, 1019 (P|O|Me); MS m/z (%): 305 (M+ , 21), 196 (100), 194 (18), 109 (12), 104 (64), 91
(18), 77 (75); Anal. Calcd for C16 H20 NO3 P: C, 62.94; H, 6.60; N, 4.59. Found: C, 62.90; H, 6.74; N, 4.50.
Compound 12: Yellow solid, mp 92-94 ◦ C. 1 H-NMR (400 MHz, CDCl3): δ = 3.66 (d, J = 10.7 Hz,
3H), 3.89 (d, J = 10.7 Hz, 3H), 5.20 (br, 1H), 5.61 (d, J = 27.1 Hz, 1H), 6.61-6.77 (m, 3H), 6.95-7.01 (m,
1H), 7.10-7.21 (m, 4H) ppm;13 C-NMR (100 MHz, CDCl3): δ = 51.75 (d, J = 152.5 Hz), 53.54 (d, J = 7.0
Hz), 54.28 (d, J = 7.0 Hz), 113.75, 115.50, 119.07, 122.97, 125.64, 129.35, 129.83 (d, J = 2.6 Hz), 129.93 (d,
J = 2.6 Hz), 130.20, 145.77 (d, J = 14.5 Hz) ppm; 31 P-NMR (161 MHz, CDCl3): δ = 23.00 ppm; IR (KBr,
cm−1): 3313 (NH), 1246 (P=O), 1056, 1033 (P|O|Me); MS m/z (%): 345 (M+2, 3), 343 (M+ ,10), 234 (100),
198 (21), 109 (11), 107 (15), 93 (51), 77 (47); Anal. Calcd for C15 H16 ClFNO3 P: C, 52.42; H, 4.69; N, 4.08.
Found: C, 52.62; H, 4.71; N, 4.19.
Compound 13: White solid, mp 146-148 ◦ C. 1 H-NMR (400 MHz, CDCl3): δ = 3.48 (d, J = 10.4 Hz,
3H), 3.78 (s, 3H), 3.82 (d, J = 10.4 Hz, 3H), 3.92 (s, 3H), 4.42 (br, 1H), 5.30 (d, J = 24.2 Hz, 1H), 6.46-6.72
(m, 5H), 7.10-7.42 (m, 3H) ppm; 13 C-NMR (100 MHz, CDCl3): δ = 47.42 (d, J = 155.9 Hz), 53.67 (d, J =
6.9 Hz), 53.81 (d, J = 6.9 Hz), 55.31, 55.84, 98.55(d, J = 2.0 Hz), 104.93 (d, J = 2.5 Hz), 113.88, 116.21,
118.49, 129.08 (d, J = 4.7 Hz), 129.55, 145.87 (d, J = 14.7 Hz), 158.17 (d, J = 6.1 Hz), 160.63 (d, J = 2.6
Hz) ppm; 31 P-NMR (161 MHz, CDCl3): δ = 26.21 ppm; IR (KBr, cm−1): 3290 (NH), 1233 (P=O), 1050,
1027 (P|O|Me); MS m/z (%): 351 (M+ , 24), 242 (100), 227 (10), 149 (48), 109 (21), 93 (30), 77 (20); Anal.
Calcd for C17 H22 NO5 P: C, 58.18; H, 6.31; N, 3.99. Found: C, 58.28; H, 6.44; N, 3.87.
Results and discussion
Initially, we tried to optimize the amount of PPA-SiO2 for the reaction between benzaldehyde, aniline, and
trimethyl phosphite under solvent-free conditions at 80 ◦ C (Table 1). As can be seen in Table 1, maximum
yield was obtained with 0.05 g (0.025 mmol H+) of the catalyst.
Table 1. Optimization of the amount of PPA-SiO2 for the reaction between benzaldehyde, aniline, and trimethyl
phosphite under solvent-free conditions at 80 ◦ C.
Entry Catalyst (g) Time (min) Yield (%)a
1
2
3
4
5
0.01
0.02
0.03
0.05
0.1
80
65
45
35
10
81
89
94
97
96
aIsolated yields.
Hence, several reactions between different aldehydes, amines, and trialkyl phosphites were examined in
the presence of PPA-SiO2 as a catalyst under solvent-free conditions at 80 ◦ C. The results are summarized in
Table 2.
567

Silica supported polyphosphoric acid..., M. T. MAGHSOODLOU, et al.,
Table 2. The synthesis of α-amino phosphonates catalyzed by PPA-SiO2 .
Entry
1
Ar1
Ph
Ar2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
R
Time (min) Yield (%)a
Ref.b
25
31
28
26
28
32
31
29
28
31
–
Me
Et
35
120
80
97
95
94
95
91
95
92
95
92
95
96
98
98
98
92
94
95
94
96
91
93
95
2
Ph
3
3-NO2-C6H4
4-NO2-C6H4
4-NO2-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-NMe2-C6H4
4-F-C6H4
Et
4
Me
Et
15
5
80
6
Me
Et
20
7
100
20
8
Me
Et
9
90
10
11
12
13
14
15
16
17
18
19
20
21
4-Me-C6H4
2-Me-C6H4
2-Cl-6-F-C6H3
2,4-di-OMe-C6H3
2,5-di-OMe-C6H3
3-NO2-C6H4
4-NO2-C6H4
Ph
Et
180
45
Me
Me
Me
Me
10
–
35
–
35
36
24
25
20
33
33
31
25
33
3-NO2-C6H4 Et
4-NO2-C6H4 Me
4-OMe-C6H4 Et
115
25
100
35
Ph
4-Cl-C6H4
4-Me-C6H4
4-F-C6H4
Me
Me
Et
Ph
30
4-OMe-C6H4
4-OMe-C6H4
4-NO2-C6H4
130
40
4-OMe-C6H4 Me
4-OMe-C6H4 Me
22
15
a
Yields refer to the pure isolated products.
bAll known products have been reported previously in the literature and were characterized by
comparison of IR and NMR spectra with authentic samples.
Each benzaldehyde with electron-deficient or electron-releasing groups reacts efficiently with aniline or
substituted aniline to give the corresponding α-amino phosphonates in high to excellent yields. Sensitive
functionality groups such as NO2 , NMe2 , OMe, F, and Cl were unaffected during the reaction. In all cases
the one-pot three-component reaction proceeded smoothly to yield the corresponding α-amino phosphonates
exclusively without any undesired side products. Moreover, on the basis of experimental results, the rate of
all reactions in the presence of trimethyl phosphite was increased in comparison with triethyl phosphite under
constant conditions. The wide applicability of the present method is evident from the fact that it is tolerant
towards various functional groups including alkoxy, halides, and nitro groups. We have also prepared 3 new
analogues of these compounds in excellent yields (entries 11-13).
The reusability of the catalyst is an important factor from economical and environmental point of views
and has attracted much attention in recent years. Thus, the reusability of PPA-SiO2 was examined in the
reaction between 2,4-dimethoxy benzaldehyde, aniline, and trimethyl phosphite under solvent-free conditions at
568

Silica supported polyphosphoric acid..., M. T. MAGHSOODLOU, et al.,
80 ◦ C. As PPA-SiO2 is a heterogeneous catalyst, it was separated and reused after being washed with methanol
and drying at 100 ◦ C for 30 min. The results showed that the catalyst can be used 5 times without loss of its
activity (Table 3).
Table 3. Investigation of reusability of the catalyst in the reaction between 2,4-dimethoxy benzaldehyde, aniline, and
trimethyl phosphite in the presence of PPA-SiO2 .
Run no. Yield (%)a
1
98
96
92
90
86
2
3
4
5
aIsolated yields
Conclusion
We have developed a novel and efficient method for the synthesis of α-amino phosphonates with the one-
pot three-component reaction under thermal solvent-free conditions. The use of PPA-SiO2 as an efficient,
inexpensive, easy to handle, non-toxic, and reusable heterogeneous catalyst makes the present procedure eco-
friendly and economically acceptable. In addition, the thermal solvent-free green procedure offers noteworthy
advantages such as short reaction times, easy work-up, and high to excellent yields, which make this method a
valid contribution to the existing methodologies.
Acknowledgements
We gratefully acknowledge the funding support received for this project from the Research Council of the
University of Sistan and Baluchestan.
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