Tween-20: An efficient catalyst for one-pot synthesis of α-aminophosphonates in aqueous media

Article abstract of DOI:10.1080/10426507.2011.631641

A green one-pot three-component synthesis has been developed for α-aminophosphonates by condensation of aldehydes, amines, and diethylphosphite by using nonionic surfactant Tween-20 as catalyst in aqueous media. The results showed that this synthetic rout

Full text of DOI:10.1080/10426507.2011.631641

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Phosphorus, Sulfur, and Silicon and the
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Tween-20: An Efficient Catalyst for One-
Pot Synthesis of α-Aminophosphonates in
Aqueous Media
Ch. Syama Sundar a , D. Srinivasulu a , S. K. Nayak b & C. Suresh
Reddy a
a Department of Chemistry , Sri Venkateswara University , Tirupati ,
Andhra Pradesh , India
b Bio-Organic Division , Bhabha Atomic Research Centre , Mumbai ,
Maharashtra , India
Published online: 31 Jan 2012.
To cite this article: Ch. Syama Sundar , D. Srinivasulu , S. K. Nayak & C. Suresh Reddy (2012)
Tween-20: An Efficient Catalyst for One-Pot Synthesis of α-Aminophosphonates in Aqueous
Media, Phosphorus, Sulfur, and Silicon and the Related Elements, 187:4, 523-534, DOI:
10.1080/10426507.2011.631641
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Phosphorus, Sulfur, and Silicon, 187:523–534, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.631641
TWEEN-20: AN EFFICIENT CATALYST FOR ONE-POT
SYNTHESIS OF α-AMINOPHOSPHONATES
IN AQUEOUS MEDIA
Ch. Syama Sundar,1 D. Srinivasulu,1 S. K. Nayak,2
and C. Suresh Reddy1
1Department of Chemistry, Sri Venkateswara University, Tirupati,
Andhra Pradesh, India
2Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai,
Maharashtra, India
GRAPHICAL ABSTRACT
Abstract A green one-pot three-component synthesis has been developed for α-
aminophosphonates by condensation of aldehydes, amines, and diethylphosphite by using
nonionic surfactant Tween-20 as catalyst in aqueous media. The results showed that this
synthetic route for α-aminophosphonates takes just 25–60 min for completion at 60 ◦C
and affords 64%–91% yields depending on the nature of the amine substrates. The major
advantages of this novel method are green reaction conditions with water as solvent, simple
workup, less reaction times, and high to moderate yields.
Keywords α-Aminophosphonates; Aqueous media; Three-component one-step reaction;
Tween-20
INTRODUCTION
Multicomponent, one-pot synthesis has received considerable attention because of
its wide range of applications in pharmaceutical chemistry for the creation of structural
Received 13 June 2011; accepted 10 October 2011.
The authors express their grateful thanks to Prof. C. D. Reddy, Department of Chemistry, Sri Venkateswara
University, Tirupati, for his helpful discussions and also thank BRNS, BARC, Mumbai for providing financial
assistance (2010/37C/26/BRNS/1424).
Address correspondence to C. Suresh Reddy, Department of Chemistry, Sri Venkateswara University,
Tirupati 517502, Andhra Pradesh, India. E-mail: csrsvu@gmail.com
523

524
CH. S. SUNDAR ET AL.
diversity and combinatorial libraries of drug discovery.1 Multicomponent reactions are
extremely convergent, producing remarkably high increase of molecular complexity in
a single-step operation.2 Multicomponent synthesis of α-aminophosphonates has gained
much interest in recent times, due to their structural similarity to the corresponding α-
aminophosphonic acids and transition state mimics of peptide hydrolysis.3,4 Many nat-
ural and synthetic α-aminophosphonates and their derivatives have greater prominence
as anti-HIV, cancer, biotic, bacterial, tumor, and antiviral agents.5–10 Furthermore, α-
aminophosphonates are used in agricultural industry as fungicidal, herbicidal agents, and
plant growth regulators.11–13 Consequently, different methods have been developed for their
synthesis. Among them, nucleophilic addition of phosphites to imines is an established most
useful method in which catalysts like InCl3, SnCl4, amberlite-IR 120, sulfamic acid, TiO2,
In(OTf)3, Silica sulphuric acid, Al(H2PO4)3, Mg(ClO4)2, TaCl5-SiO2, bismuth nitrate penta
hydrate, and lithium perchlorate14–25 are conveniently used. However, many of these cata-
lysts involved in their synthesis required tedious procedures and complex workups. Also,
their high preparation cost is of great concern especially with low product yields. Therefore,
development of an efficient, inexpensive, and eco-friendly synthesis for them is imperative.
In recent times, nonionic surfactant Tween-20 is used as a catalyst, emulsifier, and
complexing agent in both aqueous and nonaqueous media.26 It is one of the most commonly
used detergents in industry as solubilizer with a wide range of applications to biological
systems.27 Tween-20 solubilizes the nucleophilic reagent, as well as enhances the nucle-
ophilicity of the counterions. Besides, the surfactant properties of Tween-20 improve the
reaction kinetics by increasing interfacial area. In green chemistry, use of water as sol-
vent has attracted much attention in organic synthesis because of its unique reactivity
and selectivity that is not possible in organic solvents.28 Water is readily available, safest,
and the most nontoxic solvent in the chemical world. It is also considered as an ideal
solvent due to economical and environmental concerns.29 However, the possibility of us-
ing water as solvent is limited because the majority of reactants are sparingly soluble in
water. This solubility problem can be overcome by the use of a surfactant.30 Surfactants,
which are usually organic compounds that are amphiphilic and contain both hydropho-
bic and hydrophilic groups, have been recently employed to facilitate the reactions ‘‘in
water” (http://en.wikipedia.org/wiki/Surfactant). As a part of our continued interest in the
development of synthetic methods for the preparation of phosphonate derivatives,31–33
we found that Tween-20 can be readily used as efficient catalyst for the preparation of
α-aminophosphonates in aqueous media.
RESULTS AND DISCUSSION
In order to delineate the standard operating conditions the reaction among 6-
nitrobenzo[d][1,3]dioxole-5-carbaldehyde, diethylphosphite and aniline was selected as
a model (Scheme 1).
At room temperature, there is no sufficient quantity formation of the corresponding
α-aminophosphonates in water in the presence of Tween-20 catalyst even after 5 h of
reaction time (Table 1, Entry 1). Increase of the reaction temperature from 30 ◦C to 60 ◦C
led to formation of α-aminophosphonates up to 84% yields (Figure 1). Further increase of
temperature did not show any improvement in the yields. This reaction progress is sluggish
and did not go to completion even after 12 h of the reaction time in the absence of Tween-20
(Table 1, Entry 7). This shows that Tween-20 is essential and remarkably catalyzes these
reactions.

TWEEN-20: CATALYST FOR SYNTHESIS OF α-AMINOPHOSPHONATES
525
Scheme 1
Figure 1 The influence of temperature on the preparation of α-aminophosphonate 4a by using tween-20 in
aqueous media.
After optimization of experimental conditions with aniline, we extended this
three-component coupling reaction with several other amines keeping 6-nitrobenzo[d]
[1,3]dioxole-5-carbaldehyde and diethylphosphite as constant substrates and Tween-20
as catalyst. In all the cases, the reactions were completed within 25–60 min and gave
the corresponding α-aminophosphonates in 69%–91% isolated yields. In these reactions,
initial formation of imine intermediate is the key step for which further addition of
diethylphosphite occurs to form α-aminophosphonates. Observation of the synthetic data
(Table 2) reveals that the reaction goes smoothly with aromatic amines (4a–h) and affords
high yields. Nature and position of the substituent in the aromatic ring of the amines
Table 1 Optimization of reaction conditions for synthesis of 4a
Entry
Temperature (◦C)
Tween-20 (mol%)
Time (min/h)
Yield (%)a
1
2
3
4
5
6
7
30/RT
40
50
60
70
5
5
5
5
5
5
0
5 h
35
58
71
84
84
84
—
30 min
30 min
30 min
30 min
30 min
12 h
80
60
aIsolated yield.

526
CH. S. SUNDAR ET AL.
Table 2 Synthesis of α-aminophosphonates (4a-l)
Entry
1
Amine
Product (4)a
Time (min)
Yield (%)b
84
4a
30
30
30
30
2
3
4
4b
4c
4d
89
87
84
5
4e
30
85
6
7
8
4f
4g
4h
30
25
30
82
91
91
9
4i
4j
60
60
74
77
10
11
12
4k
4l
60
60
69
71
aThe products were characterized by NMR, IR, mass and elemental analysis.
bIsolated yields.

TWEEN-20: CATALYST FOR SYNTHESIS OF α-AMINOPHOSPHONATES
527
exert only marginal effect on the reaction rate and product yields. However, in the case of
aliphatic amine substrates (4j–l), overall reaction times are longer and product yields are
significantly low. Perhaps this anomaly maybe attributed to the varied stability of the imine
intermediate formed during the course of the reaction. Aromatic imines are resonance
stabilized to a larger extent when compared to their aliphatic analogues due to the presence
of aromatic ring in conjugation with the imine double bond.
To explore the scope and limitations of this reaction, we extended our protocol
to other aromatic and aliphatic carbonyl compounds and aromatic and aliphatic amines
under optimized conditions (Scheme 2). The reactions proceeded efficiently with aromatic
Scheme 2
amines when compared with those aliphatic amines as indicated by the data in Table 3.
However, the condensation of ketone with both aromatic and aliphatic amines gave lower
yields (Table 3, Entries 4, 8). This may perhaps be due to less electrophilic character with
Table 3 Synthesis of α-aminophosphonates from various carbonyl compounds
Entry
1
Carbonyl Compound (5)
Amine (6)
Product (7)
Time (min)
30
Yield (%)a
85
7a
2
3
4
5
6
7
8
7b
7c
7d
7e
7f
30
30
30
60
60
60
60
88
74
62
70
72
64
51
7g
7h
aIsolated yields.

528
CH. S. SUNDAR ET AL.
1
carbonyl carbon atom. All the products were characterized by H NMR, 13C NMR, IR,
and Mass spectral data.
CONCLUSIONS
A simple and environmental friendly protocol for the synthesis of α-
aminophosphonates using Tween-20 as catalyst in aqueous media is reported. The
major advantages of this procedure are operational simplicity, wide substrate scope,
high yields, and the nonuse of hazardous reagents and organic solvents. In many cases,
relatively pure products are obtained after workup, which gave analytical samples only on
one-column chromatographic run. This method being a more practical one serves as an
alternative to the existing synthetic methods for α-aminophosphonates.
EXPERIMENTAL
IR spectra were recorded in KBr pellets on a PerkinElmer 683 spectrophotometer. 1H,
13C, and 31P NMR spectra were taken on Bruker avance 500 MHz spectrometer in CDCl3
using TMS as internal standard. 31P NMR (202.44 MHz) was taken in CDCl3 using 85%
H3PO4 as external standard with broadband 1H decoupling. EI-Mass spectra were obtained
on JEOL GCMATE II GC-MS spectrometer at SAIF, IIT-Madras, Chennai. All chemicals
were purchased from Sigma Aldrich and used with out further purification. Double distilled
water was used as solvent.
General Procedure for α-Aminophosphonates (4a–l) and (7a–h).
A mixture of aldehyde (1 mmol), amine (1 mmol), diethylphosphite (1 mmol), and
Tween-20 (5 mol%) in water (3 mL) was stirred at 60 ∞C. When the reaction was com-
pleted (monitored by TLC), the reaction mixture was extracted with CH2Cl2. The extract
was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude
product obtained was subsequently purified by silica gel column chromatography using
EtOAc:hexane (1:4) as eluent.
Physical, Analytical, and Spectral data for the Compounds 4a-j.
Diethyl (6-nitrobenzo[d][1,3]dioxol-5-yl)(phenylamino)methylphosphon
◦
◦
ate (4a). Brown Solid, Yield: 84%, mp: 175 C–176 C. IR (KBr) (νmax cm−1): 3301
(NH), 1525 (N O), 1262 (P O), 749 (P–Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.16
(3H, t, J = 7.0 Hz, P–OCH2CH3), 1.29 (3H, t, J = 7.5 Hz, P OCH2CH3), 3.71–3.79 (1H,
m, P OCH2CH3), 3.94–4.01 (1H, m, P OCH2CH3), 4.08–4.16 (2H, m, P OCH2CH3),
4.60 (1H, d, J = 24.0 Hz, P CH), 5.93 (1H, s, OCH2O), 6.46–7.19 (7H, m, Ar H), 6.77
(1H, s, NH). 13C NMR (125.7 MHz, CDCl3) δ: 16.0 (d, J = 5.9 Hz, P OCH2CH3), 16.3
(d, J = 5.6 Hz, P OCH2CH3), 49.6 (d, J = 152.0 Hz, P CH), 63.5 (d, J = 7.2 Hz,
P OCH2CH3), 63.9 (d, J = 7.0 Hz, P OCH2CH3), 103.1 (C-6), 107.5 (C-9), 114.6 (C-21
and C-61), 123.5 (C-41), 128.9 (C-3), 129.3 (C-31 and C-51), 131.0 (C-1), 143.4 (C-8),
144.0 (C-4), 147.6 (C-11), 152.3 (C-2). 31P NMR (202.4 MHz, CDCl3) δ: 20.60. EI-MS
(m/z,%): 409 (M+1, 20), 408 (M+•, 100), 380 (30), 270 (50), 137 (34). Anal. Calcd for
C18H21N2O7P: C, 52.94; H, 5.18; N, 6.86. Found: C, 52.90; H, 5.12; N, 6.76.

TWEEN-20: CATALYST FOR SYNTHESIS OF α-AMINOPHOSPHONATES
529
Diethyl(4-bromophenylamino)(6-nitrobenzo[d][1,3]dioxol-
5-yl)methylphosphonate (4b)
Yellow Solid, Yield: 89%, mp: 181 ◦C–183 ◦C. IR (KBr) (νmax cm−1): 3299 (NH),
1
1525 (N O), 1260 (P O), 746 (P Caliphatic). H NMR (500 MHz, CDCl3) δ: 1.14 (3H,
t, J = 7.2 Hz, P OCH2CH3), 1.24 (3H, t, J = 7.6 Hz, P OCH2CH3), 3.76–3.82 (1H,
m, P OCH2CH3), 3.89–3.96 (1H, m, P OCH2CH3), 4.04–4.19 (2H, m, P OCH2CH3),
4.84 (1H, d, J = 26.0 Hz, P CH), 5.94 (2H, s, OCH2O), 6.50–7.05 (6H, m, Ar H),
6.93 (1H, s, NH). 13C NMR (125.7 MHz, CDCl3) δ: 16.0 (d, J = 5.9 Hz, P OCH2CH3),
16.3 (d, J = 5.6 Hz, P OCH2CH3), 50.2 (d, J = 152.2 Hz, P CH), 63.5 (d, J = 7.2 Hz,
P OCH2CH3), 63.9 (d, J = 7.0 Hz, P OCH2CH3), 103.1 (C-6), 107.5 (C-9), 110.7 (C-41),
115.1 (C-21 and C-61), 128.9 (C-3), 132.1 (C-31 and C-51), 143.3 (C-1), 144.4 (C-4), 144.5
(C-8), 147.6 (C-11), 152.3 (C-2). 31P NMR (202.4 MHz, CDCl3) δ: 20.54. EI-MS (m/z,%):
488 (M+1, 99), 486 (M+•, 100), 459 (30), 457 (30), 350 (60), 348 (55). Anal. Calcd for
C18H20BrN2O7P: C, 44.37; H, 4.14; N, 5.75. Found: C, 44.30; H, 4.09; N, 5.64.
Diethyl(4-chlorophenylamino)(6-nitrobenzo[d][1,3]dioxol-
5-yl)methylphosphonate (4c)
Yellow Solid, Yield: 87%, mp: 168 ◦C–169 ◦C. IR (KBr) (νmax cm−1): 3292 (NH),
1
1593 (N O), 1234 (P O), 752 (P Caliphatic). H NMR (500 MHz, CDCl3) δ: 1.05 (3H,
t, J = 7.5 Hz, P OCH2CH3), 1.19 (3H, t, J = 6.9 Hz, P OCH2CH3), 3.72–3.94 (2H,
m, P OCH2CH3), 4.00–4.12 (2H, m, P OCH2CH3), 5.12 (1H, d, J = 26.4 Hz, P CH),
6.01 (2H, s, OCH2O), 6.19 (1H, s, NH), 6.23–7.68 (6H, m, Ar H). 13C NMR (125.7 MHz,
CDCl3) δ: 16.2 (d, J = 5.5 Hz, P OCH2CH3), 16.4 (d, J = 5.9 Hz, P OCH2CH3), 55.7
(d, J = 152.4 Hz, P CH), 63.3 (d, J = 6.6 Hz, P OCH2CH3), 63.4 (d, J = 7.0 Hz,
P OCH2CH3), 103.4 (C-6), 114.6 (C-21 and C-61), 123.5 (C-9), 128.9 (C-1), 129.3 (C-31
and C-51), 131.0 (C-3), 139.4 (C-11), 143.4 (C-8), 144.0 (C-4), 147.6 (C-41), 152.3 (C-2).
31P NMR (202.4 MHz, CDCl3) δ: 22.02. EI-MS (m/z,%): 444 (M+1, 20), 442 (M+•, 100),
306 (35), 304 (80), 119 (22), 117 (22). Anal. Calcd for C18H20ClN2O7P: C, 48.83; H, 4.55;
N, 6.33. Found: C, 48.72; H, 4.43; N, 6.22.
Diethyl(4-fluoro-3-nitrophenylamino)(6-nitrobenzo[d][1,3]dioxol-
5-yl)methylphosphonate (4d)
◦
◦
White Solid, Yield: 84%, mp: 168 C–169 C. IR (KBr) (νmax cm−1): 3310 (NH),
1546 (N O), 1230 (P O), 747 (P–Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.12 (3H, t,
J = 7.6 Hz, P OCH2CH3), 1.31 (3H, t, J = 7.6 Hz, P OCH2CH3), 3.74–3.82 (1H, m,
P OCH2CH3), 3.88–4.12 (1H, m, P OCH2CH3), 4.15–4.30 (2H, m, P OCH2CH3), 4.82
(1H, d, J = 26.0 Hz, P CH), 5.98 (2H, s, OCH2O), 6.14–7.65 (5H, m, Ar H), 6.41 (1H,
s, NH). 13C NMR (125.7 MHz, CDCl3) δ: 16.1 (d, J = 5.8 Hz, P OCH2CH3), 16.3 (d, J =
6.2 Hz, P OCH2CH3), 51.7 (d, J = 150.4 Hz, P CH), 62.4 (d, J = 6.8 Hz, P OCH2CH3),
62.8 (d, J = 7.2 Hz, P OCH2CH3), 101.2 (C-6), 110.4 (C-21), 112.5 (C-9), 118.2 (C-51),
124.6 (C-61), 129.6 (C-1), 130.0 (C-3), 136.4 (C-31), 140.2 (C-11), 142.4 (C-41), 146.6
(C-2), 148.2 (C-4),152.4 (C-8). 31P NMR (202.4 MHz, CDCl3) δ: 22.10. EI-MS (m/z,%):
472 (M+1, 18), 471 (M+•, 100), 333 (45). Anal. Calcd for C18H19FN3O9P: C, 45.87; H,
4.06; N, 8.92. Found: C, 45.79; H, 4.01; N, 8.84.

530
CH. S. SUNDAR ET AL.
Diethyl(4-nitrophenylamino)(6-nitrobenzo[d][1,3]dioxol-
5-yl)methylphosphonate (4e)
◦
◦
Red Solid, Yield: 85%, mp: 191 C–192 C. IR (KBr) (νmax cm−1): 3296 (NH),
1
1598 (N O), 1235 (P O), 751 (P Caliphatic). H NMR (500 MHz, CDCl3) δ: 1.05 (3H,
t, J = 7.2 Hz, P OCH2CH3), 1.19 (3H, t, J = 7.8 Hz, P OCH2CH3), 3.72–3.92 (2H,
m, P OCH2CH3), 4.02–4.12 (2H, m, P OCH2CH3), 5.02 (1H, d, J = 26.4 Hz, P CH),
5.51 (s, 2H, OCH2O), 6.17 (1H, s, NH), 6.27–7.65 (6H, m, Ar H). 13C NMR (125.7
MHz, CDCl3) δ: 16.2 (d, J = 5.7 Hz, P OCH2CH3), 16.4 (d, J = 5.6 Hz, P OCH2CH3),
55.8 (d, J = 152.4 Hz, P–CH), 63.2 (d, J = 7.0 Hz, P OCH2CH3), 63.4 (d, J = 7.0 Hz,
P OCH2CH3), 101.2 (C-6), 108.0 (C-9), 115.5 (C-21 and C-61), 121.3 (C-41), 123.1 (C-3),
129.0 (C-31 and C-51), 129.2 (C-1), 144.9 (C-4), 147.4 (C-8), 147.6 (C-11), 148.0 (C-2).
31P NMR (202.4 MHz, CDCl3) δ: 21.12. EI-MS (m/z,%): 454 (M+1, 18), 453 (M+•, 100),
315 (45). Anal. Calcd for C18H20N3O9P: C, 47.69; H, 4.45; N, 9.27. Found: C, 47.58; H,
4.38; N, 9.20.
Diethyl(2-nitrophenylamino)(6-nitrobenzo[d][1,3]dioxol-
5-yl)methylphosphonate (4f)
◦
◦
Brown Solid, Yield: 82%, mp: 125 C–127 C. IR (KBr) (νmax cm−1): 3333 (NH),
1
1520 (N O), 1239 (P O), 762 (P Caliphatic). H NMR (500 MHz, CDCl3) δ: 1.10 (3H,
t, J = 8.2 Hz, P OCH2CH3), 1.22 (3H, t, J = 8.5 Hz, P OCH2CH3), 3.82–4.09 (2H,
m, P OCH2CH3), 4.14–4.26 (2H, m, P OCH2CH3), 5.32 (1H, d, J = 25.2 Hz, P CH),
5.90 (2H, s, OCH2O), 6.16 (1H, s, NH), 6.24–8.12 (6H, m, Ar H). 31P NMR (202.4 MHz,
CDCl3) δ: 24.08. Anal. Calcd for C18H20N3O9P: C, 47.69; H, 4.45; N, 9.27. Found: C,
47.61; H, 4.40; N, 9.24.
Diethyl(4-methoxyphenylamino)(6-nitrobenzo[d][1,3]dioxol-
5-yl)methylphosphonate (4g)
Yellow Solid, Yield: 91%, mp: 181 ◦C–183 ◦C. IR (KBr) (νmax cm−1): 3296 (NH),
1555 (N O), 1235 (P O), 751 (P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.16 (3H, t,
J = 7.4 Hz, P OCH2CH3), 1.30 (3H, t, J = 7.8 Hz, P OCH2CH3), 3.79 (3H, s, Ar OCH3),
3.85–3.99 (2H, m, P OCH2CH3), 4.08–4.17 (2H, m, P OCH2CH3), 4.92 (1H, d, J = 24.6
Hz, P CH), 5.94 (2H, s, OCH2O), 5.62 (1H, s, NH), 6.75–7.55 (6H, m, Ar H). 31P NMR
(202.4 MHz, CDCl3) δ: 22.20. Anal. Calcd for C19H23N2O8P: C, 52.06; H, 5.29; N, 6.39.
Found: C, 52.01; H, 5.22; N, 6.32.
Diethyl (6-nitrobenzo[d][1,3]dioxol-5-yl)
(o-tolylamino)methylphosphonate (4h)
Bright yellow Solid, Yield: 91%, mp: 157 ◦C–159 ◦C. IR (KBr) (νmax cm−1): 3348
(NH), 1547 (N O), 1242 (P O), 762 (P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.02
(3H, t, J = 7.6 Hz, P OCH2CH3), 1.15 (3H, t, J = 7.6 Hz, P OCH2CH3), 3.76–3.92 (2H,
m, P OCH2CH3), 3.96–4.14 (2H, m, P OCH2CH3), 4.80 (1H, d, J = 25.0 Hz, P CH),
5.04 (2H, s, OCH2O), 6.28 (1H s, NH), 6.65–7.58 (6H, m, Ar H). 31P NMR (202.4 MHz,
CDCl3) δ: 22.18. Anal. Calcd for C19H23N2O7P: C, 54.03; H, 5.49; N, 6.63. Found: C,
53.98; H, 5.41; N, 6.59.

TWEEN-20: CATALYST FOR SYNTHESIS OF α-AMINOPHOSPHONATES
531
Diethyl (benzylamino)(6-nitrobenzo[d][1,3]dioxol-5-yl)
methylphosphonate (4i)
◦
◦
White Solid, Yield: 74%, mp: 131 C–133 C. IR (KBr) (νmax cm−1): 3344 (NH),
1524 (N O), 1240 (P O), 760 (P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.03 (3H, t,
J = 8.5 Hz, P OCH2CH3), 1.19 (3H, t, J = 7.8 Hz, P OCH2CH3), 3.78–3.92 (2H, m,
NCH2), 3.96–4.10 (2H, m, P OCH2CH3), 4.17–4.28 (2H, m, P OCH2CH3), 4.88 (1H, d,
J = 24.6 Hz, P CH), 5.86 (2H, s, OCH2O), 6.25 (1H, s, NH), 6.45–7.52 (7H, m, Ar H).
31P NMR (202.4 MHz, CDCl3) δ: 20.12. Anal. Calcd for C19H23N2O7P: C, 54.03; H, 5.49;
N, 6.63. Found: C, 54.01; H, 5.44; N, 6.57.
Diethyl(6-nitrobenzo[d][1,3]dioxol-5-yl)(1-phenylethylamino)
methylphosphonate (4j)
Brick red Solid, Yield: 77%, mp: 125 ◦C–127 ◦C. IR (KBr) (νmax cm−1): 3265 (NH),
1
1530 (N O), 1266 (P O), 752 (P Caliphatic). H NMR (500 MHz, CDCl3) δ: 1.17 (3H,
t, J = 8.4 Hz, P OCH2CH3), 1.31 (3H, t, J = 8.6 Hz, P OCH2CH3), 1.42 (3H, d, J =
15.8 Hz, CHCH3), 3.72–3.85 (2H, m, P OCH2CH3), 3.92–4.08 (2H, m, P OCH2CH3),
4.18–4.31 (1H, m, NCH), 4.82 (1H, d, J = 24.2 Hz, P CH), 5.98 (2H, s, OCH2O), 6.46
(1H, s, NH), 6.57–7.82 (7H, m, Ar H). 31P NMR (202.4 MHz, CDCl3) δ: 21.92. Anal.
Calcd for C20H25N2O7P: C, 55.05; H, 5.77; N, 6.42. Found: C, 55.01; H, 5.72; N, 6.37.
Diethyl (6-nitrobenzo[d][1,3]dioxol-5-yl)(propylamino)
methylphosphonate (4k)
◦
◦
White Solid, Yield: 69%, mp: 144 C–146 C. IR (KBr) (νmax cm−1): 3255 (NH),
1
1565 (N O), 1254 (P O), 746 (P Caliphatic). H NMR (500 MHz, CDCl3) δ: 0.94 (3H,
t, J = 8.6 Hz, CH2CH3), 1.04 (3H, t, J = 6.8 Hz, P OCH2CH3), 1.18 (3H, t, J = 7.2
Hz, P OCH2CH3), 1.40-1.56 (2H, m, CH2CH2CH3), 2.42–2.56 (2H, m, NHCH2CH2),
3.80–3.99 (2H, m, P OCH2CH3), 4.14–4.26 (2H, m, P OCH2CH3), 4.86 (1H, d, J =
24.4 Hz, P CH), 5.99 (2H, s, OCH2O), 6.32 (1H, s, NH), 6.82–7.02 (2H, m, Ar H). 31
P
NMR (202.4 MHz, CDCl3) δ: 20.81. Anal. Calcd for C15H23N2O7P: C, 48.13; H, 6.19; N,
7.48. Found: C, 48.09; H, 6.11; N, 7.40.
Diethyl (butylamino)(6-nitrobenzo[d][1,3]dioxol-5-yl)
methylphosphonate (4l)
◦
◦
Brown Solid, Yield: 71%, mp: 187 C–189 C. IR (KBr) (νmax cm−1): 3310 (NH),
1
1525 (N O), 1230 (P O), 747 (P Caliphatic). H NMR (500 MHz, CDCl3) δ: 0.92 (3H,
t, J = 8.8 Hz, CH2CH3), 1.12 (3H, t, J = 7.6 Hz, P OCH2CH3), 1.22 (3H, t, J = 6.8
Hz, P OCH2CH3), 1.35–1.40 (2H, m, CH2CH2CH3), 1.44–1.49 (2H, m, CH2CH2CH2),
2.55–2.63 (2H, m, NHCH2CH2), 3.88–4.12 (2H, m, P OCH2CH3), 4.15–4.30 (2H, m,
P OCH2CH3), 5.02 (1H, d, J = 25.0 Hz, P CH), 5.94 (2H, s, OCH2O), 6.14 (1H, s,
NH), 6.92–7.24 (2H, m, Ar H). 31P NMR (202.4 MHz, CDCl3) δ: 21.02. Anal. Calcd for
C16H25N2O7P: C, 49.48; H, 6.49; N, 7.21. Found: C, 49.41; H, 6.35; N, 7.12.

532
CH. S. SUNDAR ET AL.
Diethyl (4-methoxyphenyl)(phenylamino)methylphosphonate (7a)
Viscous Liquid, Yield: 85%. IR (KBr) (νmax cm−1): 3312 (NH), 1232 (P O), 749
1
(P Caliphatic). H NMR (500 MHz, CDCl3) δ: 1.05 (3H, t, J = 7.2 Hz, P OCH2CH3),
1.20 (3H, t, J = 7.4 Hz, P OCH2CH3), 3.52 (3H, s, Ar OCH3), 3.72–4.04 (2H, m,
P OCH2CH3), 4.08–4.24 (2H, m, P OCH2CH3), 4.63 (1H, d, J = 25.2 Hz, P CH), 5.45
(1H, s, NH), 6.50–7.34 (9H, m, Ar H). 31P NMR (202.4 MHz, CDCl3) δ: 20.04. Anal.
Calcd for C18H24NO4P: C, 61.88; H, 6.92; N, 4.01. Found: C, 61.76; H, 6.84; N, 3.94.
Diethyl benzo[d][1,3]dioxol-5-yl(phenylamino)methylphosphonate (7b)
Yellow Solid, Yield: 88%, mp: 162 ◦C–164 ◦C. IR (KBr) (νmax cm−1): 3308 (NH),
1264 (P O), 755 (P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.12 (3H, t, J = 7.8 Hz,
P OCH2CH3), 1.18 (3H, t, J = 7.4 Hz, P OCH2CH3), 3.92–4.10 (2H, m, P OCH2CH3),
4.14–4.20 (2H, m, P OCH2CH3), 4.52 (1H, d, J = 24.8 Hz, P CH), 5.45 (2H, s, OCH2O),
6.77 (1H, s, NH), 6.94–8.45 (8H, m, Ar H). 31P NMR (202.4 MHz, CDCl3) δ: 21.15. Anal.
Calcd for C18H22NO5P: C, 59.50; H, 6.10; N, 3.85. Found: C, 59.45; H, 6.01; N, 3.74.
(E)-Diethyl 3-phenyl-1-(phenylamino)allylphosphonate (7c)
◦
◦
White Solid, Yield: 74%, mp: 103 C–105 C. IR (KBr) (νmax cm−1): 3328 (NH),
1258 (P O), 759 (P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.09 (3H, t, J = 6.8 Hz,
P OCH2CH3), 1.21 (3H, t, J = 7.2 Hz, P OCH2CH3), 3.54–3.78 (2H, m, P OCH2CH3),
3.90-4.12 (2H, m, P OCH2CH3), 5.02 (1H, d, J = 24.8 Hz, P CH), 5.45 (1H, d, J = 7.8
Hz, Ar CH = CH), 5.68 (1H, d, J = 9.2 Hz, Ar CH = CH), 6.12 (1H, s, NH), 7.14–8.28
(10H, m, Ar H). 31P NMR (202.4 MHz, CDCl3) δ: 20.64. Anal. Calcd for C19H24NO3P:
C, 66.07; H, 7.00; N, 4.06. Found: C, 66.00; H, 6.91; N, 3.96.
Diethyl 1-(phenylamino)cyclohexylphosphonate (7d)
◦
◦
White Solid, Yield: 62%, mp: 94 C–96 C. IR (KBr) (νmax cm−1): 3324 (NH),
1257 (P O), 758 (P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.09 (3H, t, J = 7.0 Hz,
P OCH2CH3), 1.18 (3H, t, J = 7.4 Hz, P OCH2CH3), 1.57–1.64 (2H, m, CH2CH2CH2),
1.66–174 (2H, m, CH2CH2CH2), 1.78–1.87 (2H, m, CH2CH2CH2), 1.90 (2H, t, J = 9.2 Hz,
CH2CO), 1.96 (2H, t, J = 9.0 Hz, CH2CO), 3.71–3.89 (2H, m, P OCH2CH3), 4.01–4.16
(2H, m, P OCH2CH3), 5.42 (1H, d, J = 24.4 Hz, P CH), 6.41 (1H, s, NH), 6.52–7.52
(5H, m, Ar H). 31P NMR (202.4 MHz, CDCl3) δ: 21.42. Anal. Calcd for C16H26NO3P: C,
61.72; H, 8.42; N, 4.50. Found: C, 61.64; H, 8.36; N, 4.42.
Diethyl (4-methoxyphenyl)(propylamino)methylphosphonate (7e)
Viscous Liquid, Yield: 70%, IR (KBr) (νmax cm−1): 3345 (NH), 1254 (P O), 751
(P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 0.91 (3H, t, J = 8.4 Hz, CH2CH3), 1.08 (3H,
t, J = 7.4 Hz, P OCH2CH3), 1.18 (3H, t, J = 7.2 Hz, P OCH2CH3), 1.45–1.59 (2H, m,
CH2CH2CH3), 2.52–2.64 (2H, m, NHCH2CH2), 3.65 (3H, s, Ar OCH3), 3.82–3.96 (2H,
m, P OCH2CH3), 4.04–4.19 (2H, m, P OCH2CH3), 5.07 (1H, d, J = 24.2 Hz, P CH),
6.45 (1H, s, NH), 6.99–7.68 (4H, m, Ar H). 31P NMR (202.4 MHz, CDCl3) δ: 21.12. Anal.
Calcd for C15H26NO4P: C, 57.13; H, 8.31; N, 4.44. Found: C, 57.07; H, 8.24; N, 4.32.

TWEEN-20: CATALYST FOR SYNTHESIS OF α-AMINOPHOSPHONATES
533
Diethyl benzo[d][1,3]dioxol-5-yl(propylamino)methylphosphonate (7f)
◦
◦
White Solid, Yield: 72%, mp: 132 C–134 C. IR (KBr) (νmax cm−1): 3255 (NH),
1254 (P O), 746 (P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 0.98 (3H, t, J = 8.8 Hz,
CH2CH3), 1.02 (3H, t, J = 7.4 Hz, P OCH2CH3), 1.12 (3H, t, J = 7.8 Hz, P OCH2CH3),
1.48–1.60 (2H, m, CH2CH2CH3), 2.52–2.68 (2H, m, NHCH2CH2), 3.74–3.92 (2H, m,
P OCH2CH3), 4.04–4.20 (2H, m, P OCH2CH3), 5.12 (1H, d, J = 22.8 Hz, P CH), 6.07
(2H, s, OCH2O), 6.45 (1H, s, NH), 6.84–7.14 (3H, m, Ar H). 31P NMR (202.4 MHz,
CDCl3) δ: 22.08. Anal. Calcd for C15H24NO5P: C, 54.71; H, 7.35; N, 4.25. Found: C,
54.64; H, 7.28; N, 4.17.
(E)-Diethyl 3-phenyl-1-(propylamino)allylphosphonate (7g)
Yellow Solid, Yield: 64%, mp: 103 ◦C–105 ◦C. IR (KBr) (νmax cm−1): 3328 (NH),
1258 (P O), 759 (P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.02 (3H, t, J = 8.4 Hz,
CH2CH3), 1.12 (3H, t, J = 7.0 Hz, P OCH2CH3), 1.22 (3H, t, J = 7.2 Hz, P OCH2CH3),
1.44–1.54 (2H, m, CH2CH2CH3), 2.47–2.56 (2H, m, NHCH2CH2), 3.85–3.99 (2H, m,
P OCH2CH3), 4.07–4.22 (2H, m, P OCH2CH3), 4.52 (1H, d, J = 24.8 Hz, P CH), 5.57
(1H, d, J = 7.6 Hz, Ar CH = CH), 5.99 (1H, d, J = 10.4 Hz, Ar CH = CH), 6.44 (1H,
s, NH), 7.17–8.47 (5H, m, Ar H). 31P NMR (202.4 MHz, CDCl3) δ: 21.14. Anal. Calcd
for C16H26NO3P: C, 61.72; H, 8.42; N, 4.50. Found: C, 61.65; H, 8.37; N, 4.44.
Diethyl 1-(propylamino)cyclohexylphosphonate (7h)
White Solid, Yield: 51%, mp: 129 ◦C–131 ◦C. IR (KBr) (νmax cm−1): 3339 (NH), 1229
(P O), 745 (P Caliphatic). 1H NMR (500 MHz, CDCl3) δ: 1.02 (3H, t, J = 8.0 Hz, CH2CH3),
1.09 (3H, t, J = 7.4 Hz, P OCH2CH3), 1.18 (3H, t, J = 7.6 Hz, P OCH2CH3), 1.40–1.64
(2H, m, CH2CH2CH3), 1.68–1.74 (2H, m, CH2CH2CH2), 1.78–1.84 (2H, m, CH2CH2CH2),
1.85–1.90 (2H, m, CH2CH2CH2), 1.94 (2H, t, J = 9.2 Hz, CH2CO), 1.99 (2H, t, J = 9.8 Hz,
CH2CO), 2.51–2.68 (2H, m, NHCH2CH2), 3.88–4.12 (2H, m, P OCH2CH3), 4.18–4.42
(2H, m, P OCH2CH3), 5.24 (1H, d, J = 24.0 Hz, P CH), 6.32 (1H, s, NH), 6.43–8.12
(5H, m, Ar H). 31P NMR (202.4 MHz, CDCl3) δ: 20.32. Anal. Calcd for C13H28NO3P: C,
56.30; H, 10.18; N, 5.05. Found: C, 56.24; H, 10.11; N, 4.97.
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