Solvent-free sonochemical preparation of α-aminophosphonates catalyzed by 1-hexanesulphonic acid sodium salt

Article abstract of DOI:10.1016/j.ultsonch.2010.02.002

1-Hexanesulphonic acid sodium salt was found to be an efficient catalyst for the green synthesis of α-aminophosphonates by the coupling of aldehydes/ketone, an amine and triethyl phosphite under ultrasound irradiation at ambient temperature for appropriate time to furnish the desired product in good to excellent yield under solvent-free condition. This catalyst provides clean conversion; greater selectivity and easy workup make this protocol practical and economically attractive.

Full text of DOI:10.1016/j.ultsonch.2010.02.002

Ultrasonics Sonochemistry 17 (2010) 760–763
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Short Communication
Solvent-free sonochemical preparation of
1-hexanesulphonic acid sodium salt
a-aminophosphonates catalyzed by
*
Kirti S. Niralwad, Bapurao B. Shingate, Murlidhar S. Shingare
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 January 2010
Received in revised form 2 February 2010
Accepted 2 February 2010
Available online 8 February 2010
1-Hexanesulphonic acid sodium salt was found to be an efficient catalyst for the green synthesis of
a-
aminophosphonates by the coupling of aldehydes/ketone, an amine and triethyl phosphite under ultra-
sound irradiation at ambient temperature for appropriate time to furnish the desired product in good to
excellent yield under solvent-free condition. This catalyst provides clean conversion; greater selectivity
and easy workup make this protocol practical and economically attractive.
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
1-Hexanesulphonic acid sodium salt
a-Aminophosphonates
Aldehydes/ketone
Amines
Triethyl phosphite
Ultrasonication
1. Introduction
formation of many side products. Consequently, there is still needs
to develop a more efficient, simple, milder and high yield protocol
Phosphonic acids and their phosphonate derivatives are of im-
mense interest in synthetic organic chemistry due to their biolog-
ical activities [1]. They are employed in synthetic operations
leading to carbon–carbon bond formation [2] and as transition
state analogues in production of antibody catalysts for a wide vari-
ety of reactions [3]. In recent years, considerable interest has been
for the synthesis of a-aminophosphonates.
Ultrasonication has increasingly been used in organic synthesis
in the last three decades. It has been demonstrated as an alterna-
tive energy source for organic reactions ordinarily accomplished
by heating. A great number of organic reactions can be carried
out in short reaction time, high yields and mild reaction condition
under ultrasonication [21]. The use of ultrasound-irradiation tech-
nique for activating various reactions is well documented in the lit-
erature such as Reformatsky reaction [22], Pinacol–pinacolone
reaction [23], Ullmann condensation [24] and Suzuki cross-cou-
pling [21a].
focused on the synthesis of
are considered to be structural analogues of the corresponding
amino acids and transition state mimics of peptide hydrolysis. In
these connections, the utilities of -aminophosphonates as peptide
a-aminophosphonates, because they
a
-
a
mimics [4], enzymes inhibitors [5], haptens of catalytic antibodies
[6], antibiotics and pharmacologic agents [7] are well documented.
A number of synthetic methods for the preparation of a-amino-
phosphonates have been carried out under solvent-free conditions
A search of the literature revealed that the 1-hexanesulphonic
acid sodium salt [25] liberates corresponding acid with extreme
wide applications such as sulphonation of alkanes [26]. However,
there are very few reports using hexanesulphonic acid sodium salt
as a catalyst in the organic transformation [27]. For the first time
we herein report the use of 1-hexanesulphonic acid sodium salt
in the presence of TFA [8], TsCl [9], LiClO4 [10], Mg(ClO4)2 [11], me-
tal triflate [12]. The
in organic solvents using In(OTf)3/MgSO4 [13], GaI3 [14], BiCl3
[15], Cu(OTf)2 [16], SbCl3/Al2O3 [17]. The synthesis of -amino-
a-aminophosphonates also been synthesized
a
for the synthesis of a-aminophosphonates under ultrasound irradi-
phosphonates have also been carried out in presence of ionic liq-
uids [18], Lewis acid–surfactant-combined catalyst [19] and even
in absence of solvent and catalyst [20]. However, most of these
procedures are sluggish, requires long reaction time, use of strong
acidic condition, unsatisfactory yield, which also suffer from the
ation and solvent-free condition.
2. Experimental
Melting points were determined in open capillaries in a paraffin
bath and are uncorrected. IR spectra were recorded on a Bruker
spectrophotometer using KBr discs, and the absorption bands are
* Corresponding author.
E-mail address: msshingare11@gmail.com (M.S. Shingare).
expressed in cmÀ1 1H NMR spectra were recorded on a Varian
.
1350-4177/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2010.02.002

K.S. Niralwad et al. / Ultrasonics Sonochemistry 17 (2010) 760–763
761
Table 1
AS 400 MHz spectrometer in CDCl3/DMSO-d6, chemical shifts (d)
Effect of catalyst concentration on model reaction.a
are in ppm relative to TMS, and coupling constants (J) are ex-
pressed in Hertz (Hz). Mass spectra were taken on a Macro mass
spectrometer (Waters) by electro-spray method (ES). Bandelin
Sonorex (with a frequency of 35 kHz and a nominal power
200 W) ultrasonic bath was used for ultrasonic irradiation. Built-
in heating, 30–80 °C thermostatically adjustable. The reaction ves-
sel placed in side the ultrasonic bath containing water.
Entry
Catalyst (mol%)
Yieldb (%)
1
2
3
4
5
6
2
4
6
8
10
12
56
63
78
85
94
94
a
Reaction of benzaldehyde, aniline and triethyl phosphite in presence of 1-
3. General procedure
hexanesulphonic acid sodium salt under ultrasonic waves and solvent-free condi-
tion for 15 min.
b
A mixture of substituted aldehydes/ketone (1 mmol), amine
(1 mmol), and triethyl phosphite (1.2 mmol) were placed in a
round bottom flask. Further 1-hexanesulphonic acid (10 mol%)
was added, this mixture was irradiated under ultrasonic irradiation
at ambient temperature for the precised time. After the completion
of reaction as monitored by TLC; 20 mL ice cold water was added to
the reaction mixture and product was extracted by chloroform
(2 Â 25 mL). The organic layer washed by brine (2 Â 20 mL) and
dried over anhydrous sodium sulphate. The solvent was distilled
out on rota-evaporator under reduced pressure to afford the pure
products. The products 4(a–n) were confirmed by their spectral
data after comparisons with authentic samples [31], IR, 1H NMR,
mass spectra and melting point.
Isolated yield.
Table 2
Optimization of solvent effect on the model reaction.a
Entry
Solvent
Time (min)
Yieldb (%)
1
1
2
3
4
5
6
Water
Ethanol
15
15
15
15
15
15
15
20
65
52
68
54
63
94
Methanol
Dichloromethane
Toluene
Acetonitrile
Solvent-free
a
Reaction of benzaldehyde, aniline and triethyl phosphite catalyzed by 1-hex-
anesulphonic acid sodium salt (10 mol%) under ultrasonic waves for 15 min.
4. Results and discussion
b
Isolated yield.
In the continuation of our research work of developing methods
in various organic transformations [28–30]. Herein, we have devel-
vent-free condition, we got the excellent yield of product. The ob-
tained results summarized in Table 2. We have also discussed the
effect of ultrasonic irradiation. When the model reaction was car-
ried out under conventional method it gave comparatively low
yields of products, while at the same time the model reaction car-
ried in the influence of ultrasonic irradiation it gives excellent
yields of product in short reaction time (Table 3).
After optimizing the conditions, the generality of this method
was examined by the reaction of several substituted aryl/hetero-
aryl aldehydes/ketone, amine and triethyl phosphite using 1-hex-
anesulphonic acid as a catalyst under ultrasound irradiation, the
results are shown in Table 3. Here, we have carried out the similar
reaction with various aromatic/heteroaromatic aldehydes contain-
ing electron donating or electron withdrawing functional groups at
different positions but it did not showed any remarkable differ-
ences in the yields of product and reaction time. Further study of
ketones revealed that it gives very low yields of products even after
prolonged reaction time (Table 3, entries 13 and 14). All the syn-
thesized compounds were characterised by spectral data and com-
pared (MS, NMR, and IR) with authentic sample. This comparison
revealed that the compounds synthesized by this newly developed
method were exactly similar in all aspects to the reference com-
pounds [18]. The developed methodology is simple and a good
oped methodology for the synthesis of
a-aminophosphonates
using 1-hexanesulphonic acid sodium salt, which makes use of
mild catalyst under solvent-free condition over the reported proce-
dure as depicted in Scheme 1.
Here we have carried out the reaction of benzaldehyde (1a),
aniline (2) and triethyl phosphite (3) catalyzed by 1-hexanesul-
phonic acid sodium salt under solvent-free condition and ultra-
sonic irradiation, it has been considered as a standard model
reaction.
We also have studied the catalyst concentration on model reac-
tion. We have varied the concentration of catalyst to 2, 4, 6, 8, 10,
and 12 mol%. The result revealed that, when the reaction was car-
ried out in the presence of 2, 4, 6 mol% of catalyst it gave lower
yield of product even after prolonged reaction time. At the same
time when the concentration of catalyst was 10 or 12 mol% we
got the excellent yields of product in short span. Even after increas-
ing the catalyst concentration the yields of the products were
found to be constant. So, the use of 10 mol% of catalyst is sufficient
to push the reaction forward. The obtained results summarized in
Table 1.
Further, we have also studied the effect of solvents on model
reaction. Here, we have kept the concentration of catalyst constant
on model reaction and varied the solvents condition like water,
ethanol, methanol, dichloromethane, toluene, acetonitrile and sol-
vent-free, the observation revealed that in all the solvents the
yields of the products were found to be low but in case of sol-
contribution in the field of
a-aminophosphonates.
5. Conclusion
1-Hexanesulphonic acid sodium salt was found to be mild and
effective catalyst in green synthesis of -aminophosphonate under
a
ultrasonic irradiation and solvent-free condition. The use of this
catalyst provides faster conversion; greater selectivity and easy
workup which make this manipulation practical and economically
O
1-hexanesulphonic
acid sodium salt
O
P
O
R
R''-NH2
P(OEt)3
O
R
R'
)))))
R''
attractive. We believed that, sonochemical synthesis of
a-amino-
N
H
R'= H, R
phosphonates using 1-hexanesulphonic acid sodium salt as a cata-
lyst promoted methodology will be a valuable contribution in the
field of phosphorous chemistry as compared to the existing
processes.
R'
4(a-n)
1
(a-n)
2
3
Scheme 1.

762
K.S. Niralwad et al. / Ultrasonics Sonochemistry 17 (2010) 760–763
Table 3
Sonochemical effect on the synthesis of a-aminophosphonates.
Entry
1
Product
Aldehyde/ketone
Aniline
With USa
Time (min)
15
Without USb
Time (min)
60
Yieldc.d(%)
94
Yieldc,d (%)
75
4a
CHO
NH2
NH2
2
3
4
5
4b
4c
4d
4e
12
12
15
20
92
94
89
87
60
60
60
60
70
78
72
68
CHO
H3C
CHO
NH2
NH2
NH2
H3CO
CHO
O2N
Cl
CHO
Cl
6
7
4f
18
15
88
86
60
60
65
69
Cl
CHO
NH2
NH2
4g
CHO
HO
O
8
4h
30
80
60
62
NH2
NH2
CHO
9
4i
4j
35
15
82
90
60
60
65
70
CHO
CHO
S
10
NH2
H3C
11
12
4k
4l
20
20
88
86
60
60
72
73
CHO
CHO
NH2
Cl
NH
H3CO
13
14
4m
4n
120
140
43
32
60
60
30
33
O
NH2
NH2
O
a
b
c
Reaction of aldehyde/ketone, amine, triethylphosphite in presence of 1-hexanesulphonic acid sodium salt (10 mol%) under ultrasonic waves for 15 min.
Reaction of aldehyde/ketone, amine, triethylphosphite in presence of 1-hexanesulphonic acid sodium salt (10 mol%) under stirring at ambient temperature.
Isolated yield.
d
Compounds were characterised by 1H NMR, MS spectral data and were compared with the reference compounds [31].

K.S. Niralwad et al. / Ultrasonics Sonochemistry 17 (2010) 760–763
763
(c) S. Lee, J.K. Lee, C.E. Song, D.C. Kim, Bull. Korean Chem. Soc. 23 (2002) 667;
(d) S. Lee, J.H. Park, J. Kang, J.K. Lee, Chem. Commun. (2001) 1698.
[19] K. Manabe, S. Kobayashi, Chem. Commun. (2000) 669.
[20] S. Chandrasekhar, C. Narsihmulu, S.S. Sultana, B. Saritha, S.J. Prakash, Synlett
(2003) 505.
[21] (a) R. Rajagopal, D.V. Jarikote, K.V. Srinivasan, Chem. Commun. (2002) 616;
(b) B.A. Song, G.P. Zhang, S. Yang, D.Y. Hu, L.H. Jin, Ultra. Chem. 13 (2001)
1544;
Acknowledgements
The authors are thankful to University Grants Commission, New
Delhi, for awarding the fellowship and to The Head, Department of
Chemistry, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad, for his valuable support and laboratory facility.
(c) A. Gaplovsky, M. Goplosky, S. Toma, J.L. Luche, J. Org. Chem. 65 (2000)
8444.
[22] V. Singh, V. Sapehiyia, G.L. Kad, Synthesis (2003) 198.
[23] J.T. Li, Y.J. Bian, H.J. Zang, T.S. Li, Synth. Commun. 32 (2002) 547.
[24] M. Robin, V. Pique, R. Faure, J.P. Glay, J. Hetero. Chem. 39 (2002) 1083.
[25] (a) J. Weiss, V.C.H Verlags gesellschaft mbH, IInd ed., VCH Publisher, Inc., New
York, Weinheim, Germany, 1995.;
(b) H. Small, Ion Chromatography, Plenum Press, New York and London, 1989.
[26] J.L. Boyer, B. Gilot, J.P. Canselierm, Phosphorus, sulphur, and silicon related
elements 20 (1984) 259.
References
[1] B.E. Maryanoff, A.B. Reitz, Chem. Rev. 89 (1989) 863.
[2] R. Engel, Chem. Rev. 77 (1977) 349.
[3] R.A. Lerner, S.J. Benkovic, P.G. Schultz, Science 252 (1991) 659.
[4] P. Kafarski, B. Lejezak, Phosphorus, sulfur, silicon related elements 63 (1991)
193.
[5] M.C. Allen, W. Fuhrer, B. Tuck, R. Wade, J.M. Wood, J. Med. Chem. 32 (1989)
1652.
[6] R. Hirschmann, A.B. Smith, C.M. Taylor, P.A. Benkovic, S.D. Taylor, K.M. Yager,
P.A. Sprengler, S. Venkovic, J. Sci. 265 (1994) 234.
[7] (a) F.R. Atherton, C.H. Hassal, R.W. Lambert, J. Med. Chem. 29 (1986) 29;
(b) E.K. Baylis, C.D. Campell, J.G. Dingwall, J. Chem. Soc. Perkin Trans. 1 (1984)
2845.
[8] T. Akiyama, M. Sanada, K. Fuchibe, Synlett (2003) 1463.
[9] B. Kaboudin, E. Jafari, Synlett (2008) 1837.
[10] (a) N. Azizi, F. Rajabi, M.R. Saidi, Tetrahedron Lett. 45 (2004) 9233;
(b) N. Azizi, M.R. Saidi, Eur. J. Org. Chem. 23 (2003) 4630.
[11] S. Bhagat, A.K. Chakraborti, J. Org. Chem. 72 (2007) 1263.
[12] H. Firouzabadi, N. Iranpoor, S. Sobhani, Synthesis (2004) 2692.
[13] R. Ghosh, S. Maiti, A. Chakraborty, D. Maiti, J. Mol. Chem. A 53 (2004) 210.
[14] P.P. Sun, Z.X. Hu, Z.H. Huang, Synth. Commun. 34 (2004) 4293.
[15] Z.P. Zhan, J.P. Li, Synth. Commun. 35 (2005) 2501.
[16] A.S. Paraskar, A. Sudalai, Arkivoc 10 (2006) 183.
[17] K.S. Ambica, S.C. Taneja, M.S. Hundal, K.K. Kapoor, Tetrahedron Lett. 49 (2008)
2208.
[27] (a) R.S. Joshi, P.G. Mandhane, S.D. Diwakar, C.H. Gill, Ultrason. Sonochem. 17
(2010) 298;
(b) G.R. Jadhav, M.U. Shaikh, R.P. Kale, C.H. Gill, Chin. Chem. Lett. 20 (2009)
292.
[28] (a) S.S. Sonar, S.A. Sadaphal, V.B. Labade, B.B. Shingate, M.S. Shingare,
Phosphorus sulfur silicon and related elements 65 (2010) 185.;
(b) S.S. Sonar, A.H. Kategaonkar, C.H. Gill, B.B. Shingate, M.S. Shingare, Arkivoc
2 (2009) 138;
(c) R.U. Pokalwar, R.V. Hangarge, B.R. Madje, M.N. Ware, M.S. Shingare,
Phosphorous sulphur silicon related elements 183 (2008) 1461.
[29] S.B. Sapkal, K.F. Shelke, B.B. Shingate, M.S. Shingare, Tetrahedron Lett. 50
(2009) 1754.
[30] (a) K.F. Shelke, S.B. Sapkal, M.S. Shingare, Chin. Chem. Lett. 20 (2009) 283;
(b) S.S. Sonar, S.A. Sadaphal, A.H. Kategaonkar, R.U. Pokalwar, B.B. Shingate,
M.S. Shingare, Bull. Korean Chem. Soc. 30 (2009) 825.
[31] Spectral data of reprehensive compounds (4a) M.P 98–100 °C 1H NMR (CDCl3-
400 MHz): 1.13 (3H, t), 1.23 (3H, t), 3.66 (1H, ddq, J = 7.1, 11.2, 8.1 Hz), 3.97
(1H, ddq, J = 7.1, 8.1, 11.2 Hz), 4.13 (2H, m), 4.75 (1H, br, –NH), 4.78 (1H, d,
J = 17.9 Hz), 6.61 (2H, d, J = 8.5 Hz), 6.70 (1H, t, J = 7.4), 7.11 (2H, t, J = 7.4), 7.26
(1H, m), 7.34 (2H, t, J = 7.4 Hz), 7.49 (2H, m); IR (KBr) cmÀ1: 3295 (–NH), 1233
(P–O), 1103–997 (P–O–Et) Es-MI.320 (M+).
[18] (a) S.A. Sadaphal, S.S. Sonar, A.H. Kategaonkar, M.S. Shingare, Bull. Korean
Chem. Soc. 30 (2009) 1054;
(b) J.S. Yadav, B.V.S. Reddy, P. Sreedhar, Green Chem. 4 (2002) 436;