Amberlyst-15-catalyzed facile synthesis of α-amino phosphonates

Article abstract of DOI:10.1080/00397911003707188

(Chemical Equation Presented) A simple and efficient method has been developed for the synthesis of sulfonamide phosphonates from N-tosyl aldimines and dimethyl trimethylsilyl phosphite at 0 °C in the presence of Amberlyst-15 as a heterogeneous catalyst.

Full text of DOI:10.1080/00397911003707188

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Amberlyst-15–Catalyzed Facile Synthesis
of α-Amino Phosphonates
Dega Sudhakar a , Vidavalur Siddaiah a & Chunduri Venkata Rao a
a Department of Chemistry , Sri Venkateswara University , Tirupati ,
India
Published online: 03 Mar 2011.
To cite this article: Dega Sudhakar , Vidavalur Siddaiah & Chunduri Venkata Rao (2011)
Amberlyst-15–Catalyzed Facile Synthesis of α-Amino Phosphonates, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:7, 976-980, DOI:
10.1080/00397911003707188
To link to this article: http://dx.doi.org/10.1080/00397911003707188
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Synthetic Communications1, 41: 976–980, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003707188
AMBERLYST-15–CATALYZED FACILE SYNTHESIS OF
a-AMINO PHOSPHONATES
Dega Sudhakar, Vidavalur Siddaiah, and
Chunduri Venkata Rao
Department of Chemistry, Sri Venkateswara University, Tirupati, India
GRAPHICAL ABSTRACT
Abstract A simple and efficient method has been developed for the synthesis of sulfonamide
phosphonates from N-tosyl aldimines and dimethyl trimethylsilyl phosphite at 0 ꢀC in the
presence of Amberlyst-15 as a heterogeneous catalyst.
Keywords Amberlyst-15; a-amino phosphonates; dimethyl trimethylsilyl phosphite;
N-tosyl aldimines
INTRODUCTION
a-Amino phosphonates and their derivatives are important targets in synthetic
and medicinal chemistry because they possess several important biological properties
such as anticancer,[1] anti-HIV,[2] antithrombotic,[3] and antibacterial[4] activities.
They also are used as enzyme inhibitors,[5] peptide mimics,[6] and fire retardants
for cotton.[7] Additionally, they are utilized as insecticides,[8] herbicides,[9] and fungi-
cides.[10] A number of methods have been developed for the synthesis of a-amino
phosphonates and their analogs both in racemic and optically active forms.[11–16]
In general, a-amino phosphonates are prepared by the reaction of amines or imines
and carbonyl compounds with alkyl phosphites. Recently, a-amino phosphonates
have been synthesized from N-tosyl aldimines[17] and dialkyl trimethylsilyl phos-
phites. However, there are some limitations such as long reaction times, use of haz-
ardous organic solvents, and moderate yields when aliphatic aldehydes are taken as
starting materials. In addition, some of these catalysts are expensive, moisture sensi-
tive, and difficult to prepare. So, there is a need for the development of an efficient,
Received November 30, 2009.
Address correspondence to Vidavalur Siddaiah, Department of Chemistry, Sri Venkateswara
University, Tirupati 517 502, India. E-mail: sidduchem@gmail.com
976

a-AMINO PHOSPHONATES
977
cost-effective, ecofriendly process for the synthesis of a-amino phosphonates. In
recent years, heterogeneous catalysts have gained importance because of economic
and environmental considerations. The heterogeneous catalyst Amberlyst-15 has
been used in various organic transformations and syntheses because it is inexpensive
and can be easily handled or removed.[18]
RESULTS AND DISCUSSION
In continuation of our work[19] on the development of new synthetic methodol-
ogies, we have synthesized sulfonamide phosphonates by the reaction of N-tosyl
aldimines with dimethyl trimethylsilyl phosphite in the presence of Amberlyst-15
at 0 ꢀC under heterogeneous conditions in excellent yields (Scheme 1).
To achieve suitable conditions for the transformation, we investigated the
reaction of N-tosyl benzaldimine and dimethyl trimethylsilyl phosphite in various sol-
vents and solvent-free conditions in the presence of Amberlyst-15 (Table 1). We found
that the best result was obtained in CH2Cl2 at 0 ꢀC. Furthermore, the catalyst was
recovered, activated, and reused three consecutive times with only slight variations
in the yields of the product. Subsequently, a series of sulfonamide phosphonates were
prepared (Table 2) from different N-tosyl aldimines[20,21] derived from various aro-
matic, heteroaromatic, and aliphatic aldehydes under similar conditions. The N-tosyl
aldimines containing both electron-donating as well as electron-withdrawing groups
gave good yields. The aliphatic aldimine derivatives also underwent smooth conver-
sion into sulfonamide phosphonates. The reaction was completed within 2.0–3.5 h,
and the sulfonamide phosphonates were obtained in excellent yields. The physical
data [melting points, mass spectra (MS), and NMR] of known compounds were found
to be identical with those reported in the literature.[17] The N-tosyl group of the pro-
ducts can easily be deprotected to furnish the corresponding a-amino phosphonates,
which can be used to explore their biological properties.
Scheme 1. Synthesis of a-amino phosphonates from N-tosyl aldimines.
Table 1. Effect of reaction conditions
Conditions
Time (h)
Yield (%)
CH2Cl2, 0 ꢀC, Amberlyst-15
CH2Cl2, 0 ꢀC
MeCN, 0 ꢀC, Amberlyst-15
DMF, 0 ꢀC, Amberlyst-15
EtOH, 0 ꢀC, Amberlyst-15
Solvent-free, 0 ꢀC, Amberlyst-15
2
5
1
6
6
6
94
>20
>40
55
>40
>50

978
D. SUDHAKAR, V. SIDDAIAH, AND C. V. RAO
Table 2. Synthesis of a-amino phosphonates from various N-tosyl aldimines and dimethyl trimethylsilyl
phosphite in the presence of Amberlyst-15
Entry
N-Tosyl aldimines (1)
a-Amino phosphonates (3)
Time (h)
Yield (%)
3a
2
94
3b
3c
3d
3e
2.5
2.5
2.5
3.0
92
90
91
89
3f
3.5
86
3s
3h
3i
2.5
3.0
2.0
89
86
91

a-AMINO PHOSPHONATES
979
CONCLUSION
In conclusion, we have developed a facile method for the synthesis of sulfona-
mide phosphonates from N-tosyl aldimines and dimethyl trimethylsilyl phosphate
with Amberlyst-15 as a heterogeneous catalyst. Operational simplicity, mild reaction
conditions, reusability of the catalyst, and excellent yields are the notable advantages
of this method.
EXPERIMENTAL
General Experimental Procedure for the Synthesis
of a-Amino Phosphonates
N-Tosyl aldimine (1 mmol) was taken in CH2Cl2 (2 mL) under N2, and
Amberlyst-15 (30 mg) was added. The mixture was kept at 0 ꢀC. Dimethyl trimethyl-
silyl phosphite (1.2 mmol) was subsequently added, and the mixture was stirred. The
reaction was monitored by thin-layer chromatography (TLC). After completion of
the reaction, the solvent was evaporated and the reaction mass was diluted with
EtOAc. The catalyst was separated by filtration and washed with EtOAc. The filtrate
was evaporated, and the crude product was subjected to column chromatography
(silica gel, hexane–EtOAc) to obtain pure sulfonamide phosphonate.
Spectral Data for Selected Compounds
Entry 3c. Mp 156–158; 1H NMR (200 MHz, CDCl3): d 2.29 (3H, s), 3.45 (3H,
d, J ¼ 10.0 Hz), 3.90 (3H, d, J ¼ 10.0 Hz), 4.83 (1H, dd, J ¼ 24.0, 10.0 Hz), 6.77 (2H,
t, J ¼ 7.0 Hz), 7.00 (2H, d, J ¼ 8.0 Hz), 7.28–7.17 (2H, m), 7.46 (2H, d, J ¼ 8.0 Hz);
13C NMR (50 MHz, CDCl3): d 21.32, 53.49 (d, J ¼ 7.0 Hz), 54.29 (d, J ¼ 150.5 Hz),
54.94 (d, J ¼ 7.0 Hz), 115.02, 115.31, 126.98, 129.01, 129.91, 137.74, 143.06, 160.72,
164.01; ESIMS: m=z 366 [M þ Na]þ.
Entry 3e. Mp 134–136; 1H NMR (200MHz, CDCl3): d 2.17 (3H, s), 2.28 (3H, s),
2.32 (3H, s), 2.37 (3H, s), 3.33 (3H, d, J ¼ 10.0 Hz), 3.78 (3H, d, J ¼ 10.0 Hz), 5.35 (1H,
dd, J ¼ 24.0, 10.0 Hz), 5.75 (1H, brs), 6.49 (1H, s), 6.72 (1H, s), 6.98 (2H, d, J ¼ 8.0 Hz),
7.36 (2H, d, J ¼ 8.0 Hz); 13C NMR (50 MHz, CDCl3): d 20.60, 20.75, 21.34, 47.98 (d,
J ¼ 153.7 Hz), 50.83 (d, J ¼ 7.0 Hz), 52.73 (d, J ¼ 7.0 Hz), 126.58, 126.82, 128.90,
129.09, 130.86, 136.92, 137.03, 137.66, 143.06; ESIMS: m=z 421 [M þ Na]þ.
ACKNOWLEDGMENT
The authors thank the University Grants Commission, New Delhi, for
financial assistance.
REFERENCES
1. PCT Int. Appl. WO 2007045496, 2007.
2. Alonso, E.; Alonso, E.; Solis, A.; del Pozo, C. Synthesis of N-alkyl-(a-aminoalkyl)
phosphine oxides and phosphonic esters as potential HIV-protease inhibitors, starting
from a-aminoacids. Synlett 2000, 698.

980
D. SUDHAKAR, V. SIDDAIAH, AND C. V. RAO
3. Meyer, J. H.; Barlett, P. A. Macrocyclic inhibitors of penicillopepsin, 1: Design, synthesis,
and evaluation of an inhibitor bridged between P1 and P3. J. Am. Chem. Soc. 1998, 120,
4600.
4. Atherton, F. R.; Hasall, C. H.; Lambert, R. W. Synthesis and structure–activity relation-
ships of antibacterial phosphonopeptides incorporating (1-aminoethyl)phosphonic acid
and (aminomethyl)phosphonic acid. J. Med. Chem. 1986, 29, 29.
5. Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. Renin inhibitors: Synthesis of
transition-state analog inhibitors containing phosphorus acid derivatives at the scissile
bond. J. Med. Chem. 1989, 32, 1652.
6. Kafarski, P.; Lejezak, B. Natural phosphate and potassium fluoride – doped natural
phosphate. Phosphorous, Sulfur Silicon Relat. Elem. 1991, 63, 193.
7. Birum, G. H. U.S. Patent 4,032,601, 1977; Chem. Abstr. 1977, 87, 135933.
8. Emsley, J.; Hall, D. The Chemistry of Phosphorous; Harpar and Row: London, 1976.
9. Klesezynska, H.; Bornarska, D.; Bielecki, K.; Sarapak, J. Antioxidative activity of some
phenoxy and organophosphorous compounds. Cell Mol. Biol. Lett. 2002, 7, 929.
10. Smith, W. W.; Bartlett, P. A. Macrocyclic inhibitors of penicillopepsin, 3: Design, syn-
thesis, and evaluation of an inhibitor bridged between P2 and P10. J. Am. Chem. Soc.
1998, 120, 4622.
11. Changtao, Q.; Taishing, H. One-pot synthesis of a-amino phosphonates from aldehydes
using lanthanide triflate as a catalyst. J. Org. Chem. 1998, 63, 4125.
12. Ramu, B. C.; Hajra, A.; Jana, J. General procedure for the synthesis of a-amino phospho-
nates from aldehydes and ketones using indium(III) chloride as a catalyst. Org. Lett. 1999,
1, 1141.
13. Joly, G. D.; Jacobsen, E. N. Thiourea-catalyzed enantioselective hydrophosphonylation
of imines: Practical access to enantiomerically enriched a-amino phosphonicacids.
J. Am. Chem. Soc. 2004, 126, 4102.
14. Bhagat, S.; Chakraborti, A. K. An extremely efficient three-component reaction of
aldehydes=ketones, amines, and phosphites (Kabachnik–Fields reaction) for the synthesis
of a-aminophosphonates catalyzed by magnesium perchlorate. J. Org. Chem. 2007,
72, 1263.
15. Saito, B.; Egami, H.; Katsuki, T. Synthesis of an optically active Al(salalen) complex and
its application to catalytic hydrophosphonylation of aldehydes and aldimines. J. Am.
Chem. Soc. 2007, 129, 1978.
16. Bhanushali, M. J.; Nandurkar, N. S.; Jagtap, S. P.; Bhanage, B. M. ZrOCl2-8H2O: An
efficient catalyst for one-pot synthesis of a-amino phosphonates under solvent-free
conditions. Synth. Commun. 2009, 39, 845.
17. Das, B.; Balasubramanyam, P.; Krishnaiah, M.; Veeranjaneyulu, B.; Reddy, G. C. Iodine-
catalyzed efficient hydrophosphonylation of N-tosyl aldimines. J. Org. Chem. 2009, 74,
4393.
18. Das, B.; Chowdhury, N. Amberlyst-15: An efficient reusable heterogeneous catalyst
for aza-Michael reactions under solvent-free conditions. J. Mol. Catal. A: Chem. 2007,
263, 212.
19. Maheswara, M.; Siddaiah, V.; Damu, G. L. V.; Koteswara Rao, Y.; Venkata Rao, C.
A solvent-free synthesis of coumarines via Pachmann condensation using heterogeneous
catalyst. J. Mol. Catal. A: Chem. 2006, 255, 49.
20. Jennings, W. B.; Lovely, C. J. The titanium tetrachloride – induced syntheis of
N-phosphinoylimines and N-sulphonylimines directly from aromatic aldehydes. Tetra-
hedron 1991, 47, 5561.
21. Chemla, F.; Hebbe, V.; Normant, J.-F. An easy synthesis of aliphatic and aromatic
N-sulfonyl aldimines. Synthesis 2000, 75.