Convenient one-pot synthesis of α-amino phosphonates in water using p-toluenesulfonic acid as catalyst for the Kabachnik-fields reaction

Article abstract of DOI:10.1002/hc.21071

The three-component Kabachnik-Fields reaction of substituted salicylaldehydes, aromatic amine, and triphenyl phosphite in water was effectively catalyzed by p-toluenesulfonic acid to give various α-amino phosphonates in good yields. The catalyst is easily

Full text of DOI:10.1002/hc.21071

Heteroatom Chemistry
Volume 24, Number 2, 2013
Convenient One-Pot Synthesis of α-Amino
Phosphonates in Water Using
p-Toluenesulfonic Acid as Catalyst for the
Kabachnik–Fields Reaction
Mingshu Wu, Rendie Liu, and Dehui Wan
College of Chemistry and Chemical Engineering, Key Laboratory of Tropical Medicinal Plant
Chemistry, Ministry of Education, Hainan Normal University, Haikou 571158, Hainan, People’s
Republic of China
Received 14 October 2012; revised 9 December 2012, 14 December 2012
pounds with diverse biological activities such as an-
ABSTRACT: The three-component Kabachnik–
tibacterial, anti-HIV, peptidomimetics, enzyme in-
Fields reaction of substituted salicylaldehydes, aro-
hibitors, pharmacogenic agents, haptens of catalytic
matic amine, and triphenyl phosphite in water was
antibodies, herbicidals, inhibitors of serine hydro-
effectively catalyzed by p-toluenesulfonic acid to give
lases, and antitumor agents [2].
various α-amino phosphonates in good yields. The
A large number of methodologies for the syn-
catalyst is easily available and inexpensive, and the
thesis of various α-amino phosphonate compounds
ꢀC
process is green and mild.
2013 Wiley Periodi-
have been extensively developed under various
conditions. However, the one-pot synthesis of α-
aminophosphonates via the Kabachnik–Fields re-
action remains favorable because of its versa-
tile route and highly efficient reactions. Recently,
the three-component synthesis starting with alde-
hydes, amines, and diethyl phosphite or triethyl
phosphite was reported using Lewis and Brønsted
acid catalysts such as LiClO4 [3], InCl3 [4], lan-
thanide triflates/magnesium sulfate [5], TaCl5–SiO2
[6], Amberlyst-15 [7], Al2O3-MW [8], sulfamic acid
[9], scandium tris(dodecyl sulfate) [10], BF3-Et2O
[11], M(OTf)n [12], M(ClO4)n [13], lanthanide tri-
flates/ionic liquids [14], SmI2 [15], AlCl3 [16],
ZrOCl2·8H2O [17], and TiO2 [18]. The majority of
these processes suffer from some drawbacks such
as long reaction times, low yields of the products,
the requirement of a stoichiometric amount of cat-
alysts, costly metal ion, and the use of highly toxic
catalysts. Therefore, it is still necessary to develop a
more efficient method, particularly considering to-
day’s environmental concerns combined with eco-
nomic aspects.
cals, Inc. Heteroatom Chem 24:110–115, 2013; View
this article online at wileyonlinelibrary.com. DOI
10.1002/hc.21071
INTRODUCTION
The chemistry of organophosphorus compounds has
received much attention due to the unique struc-
tural features and the significant biological activities
of these compounds and, therefore utility in a wide
range of applications in the areas of industrial, agri-
cultural, and medicinal chemistry as well as their
utility as synthetic intermediates [1]. As a kind of
structural analogy to natural amino acid, α-amino
phosphonates constitute an important class of com-
Correspondence to: Mingshu Wu; e-mail: wumingshu@126.com.
Contract grant sponsor: National Natural Science Foundation
of China.
Contract grant number: 21162008.
ꢀC
2013 Wiley Periodicals, Inc.
110

Convenient One-Pot Synthesis of α-Amino Phosphonates in Water Using p-Toluenesulfonic Acid 111
p
SCHEME 1 Synthesis of α-amino phosphonates using p-toluenesulfonic acid as a catalyst in water.
terized by 1H NMR, 31P NMR, IR, and elemental
analysis.
More recently, the use of an aqueous medium
as a reaction solvent has attracted much attention.
Scandium tris(dedecyl sulfate) [19], magnesium do-
decyl sulfate [20], and thiamine hydrochloride (VB1)
[21] are reported to be effective catalysts for the
formation of α-amino phosphonates using a three-
component system consisting of aldehydes, amines,
and triethyl phosphite in an aqueous medium. How-
ever, these catalysts are expensive and not easily
available. And so we report on an ecofriendly, facile,
and efficient methodology for the synthesis of α-
amino phosphonates using p-toluenesulfonic acid as
the catalyst by a three-component Kabachnik–Fields
reaction system comprising substituted salicylalde-
hydes, amines, and triphenyl phosphite in an aque-
ous medium (Scheme 1). As shown in Scheme 1,
substituted salicylaldehydes 3 was allowed to react
with aromatic amines 4 and triphenyl phosphite us-
ing a small amount of p-toluenesulfonic acid as the
catalyst in an aqueous medium to give the title com-
pounds 1 in good yields. However, this method ap-
pears to have limited aromatic amine and some sal-
icylaldehydes, since the attempts to extend the re-
action to aliphatic amines failed. All the products
were isolated from the reaction mixture by filtra-
tion, washed with cool water, and recrystallized from
aqueous ethanol, and their structures were charac-
RESULTS AND DISCUSSION
To study the reaction in water, the reaction of sali-
cylaldehydes 3a, aniline 4a, and triphenyl phosphite
5 was tested as a model reaction at room temper-
ature in the presence of various catalysts in water
(Table 1). It was found that p-toluenesulfonic acid
(entry 1) was the catalyst of choice for the reaction
and the desired product (1a) was obtained in excel-
lent yields (80%).
After optimizing the conditions, the generality of
this method was examined by the reaction of several
substituted salicylaldehydes (3), substituted amine
(4), with triphenyl phosphate and p-toluenesulfonic
acid. The results are presented in Table 2. All α-
amino phosphonates derivatives thus obtained show
diagnostic doublets of methylene carbons bearing
phosphonate groups due to their coupling with a
phosphorus atom in their 13C NMR spectra. 31P
NMR chemical shifts of these compounds (1a, 1c,
1d, 1e, 1g) showed four signals each in the re-
gion 16.96–18.35 ppm, and other compounds (1b,
1f, 1h, 1i, 1j, 1k, 1l) showed two signals each in
Heteroatom Chemistry DOI 10.1002/hc

112 Wu et al.
TABLE 1 Optimization of the Catalyst Effect on the Model
phosphorus atom and the neighboring N H pro-
ton. The N H proton signal appeared as doublets
at δ 5.12–5.68 ppm, owing to its coupling with the
neighboring C H proton.
Reactiona
CONCLUSIONS
In conclusion, the three-component Kabachnik–
Fields reaction of substituted salicylaldehydes, aro-
matic amine, and triphenyl phosphite in water was
effectively catalyzed by p-toluenesulfonic acid to give
various α-amino phosphonates in good yields. The
method displays the advantages of green synthesis
without organic solvents involved, mild conditions,
ready operations, and an easily available catalyst.
The results showed that substituted salicylaldehydes
containing electron-withdrawing groups could not
provide better yields than ones not containing sub-
stituted groups. The influence of substituted groups
of aromatic amines on the yields does not seem ob-
vious. Unfortunately, the attempts to extend the re-
action to aliphatic amines failed.
Entry
Catalyst
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
2
2
2
2
2
2
2
2
80
65
63
73
56
53
52
75
(CH3COO)2Mn
NiCl·6H2O
CoCl·6H2O
InCl2
ZnCl2
FeCl3·6H2O
CeCl3
aReaction conditions: All reactions were carried out in 10 mL H2O at
room temperature with 1 mmol of reactants and 10% mol catalyst.
bIsolated yield.
region 16.00–18.35 ppm (Table 2). The magnetic
nonequivalence of the phosphorus atom in phospho-
nate ester groups may be due to a restricted rota-
tion at the phosphorus center by intramolecular hy-
drogen bonds between the phenolic hydoxyl group
and phosphonate ester group (2), and so the two
stereogenic centers were created. Consequently, the
four diastereoisomers should be found. The results
are in agreement with those of analogs described
EXPERIMENTAL
All melting points were determined on a Yanaco ap-
paratus (Japan) and are uncorrected. NMR spectra
were measured on a Brucker 400 NMR instrument
(Switzerland) in DMSO-d6, and chemical shifts were
expressed as units. TMS was used as an internal stan-
1
dard for H NMR, and 13C NMR and 85% H3PO4
1
in the literature [22]. In the H NMR spectra of all
compounds, the proton at the α-carbon position res-
onated as two doublets due to its coupling with the
were used as an external standard for 31P NMR
spectroscopy. IR spectra were determined as KBr
pellets on an Avatar 360 FT-IR spectrophotometer.
TABLE 2 Synthesis of α-Amino Phosphonate from Various Substituted Salicylaldehydes, Amines and Triphenyl Phosphite
Entry
1
R1
H
R2
Product
Time (h)
3
Yield (%)a
93.8
mp (◦C)
31P NMR DMSO-d6/H3PO4
C6H5
1a
126–128
17.45/17.60
17.86 /18.02
17.11/17.27
16.96/17.12
17.48/17.63
17.00/17.15
16.42/16.58
17.01/17.17
17.44/17.59
15.89/16.03
18.35/18.20
17.76/17.61
17.50/17.35
16.28/16.12
16.57/16.42
16.23/16.16
16.15/16.00
2
3
H
H
2-CH3C6H4
4-Br C6H4
1b
1c
3
4
82.2
88.8
142–143
147–148
4
5
H
H
3-NO2C6H4
4-ClC6H4
1d
1e
5
5
89.2
91.1
131–132
143–145
6
7
H
H
2,5-Cl2C6H3
4-CH3C6H4
1f
1g
5
4
82.3
82.0
146–148
136–138
8
9
10
11
12
H
5-Cl
5-Cl
5-Br
5-NO2
2-OCH3C6H4
2-CH3C6H4
2-OCH3C6H4
2-CH3C6H4
4-CH3C6H4
1h
1i
1j
1k
1l
4
5
5
5
5
91.2
86.4
83.1
83.7
83.4
148–149
158–159
159–160
151–152
143–144
aIsolated yields.
Heteroatom Chemistry DOI 10.1002/hc

Convenient One-Pot Synthesis of α-Amino Phosphonates in Water Using p-Toluenesulfonic Acid 113
Elemental analysis was carried out with a Yanaco
Chncorder MT-3 analyzer (Japan).
(100 MHz, DMSO-d6) δ: 46.2 (d, JPC = 161.7 Hz),
108.2, 115.0, 115.2, 119.3, 120.1,120.2, 120.6, 120.7,
121.3, 125.1, 125.3, 129.7, 129.8, 131.4, 146.4, 150.0,
150.1, 155.3; IR (KBr) ν: 3418 (NH), 3020 (Ph OH),
General Procedure for the Synthesis of the
α-Aminophosphonates 1
1244 (P O), 1072 (P
O C); Found: C, 58.79; H,
4.13, N, 2.78. Calcd. for C25H21BrNO4P (509.04); C,
58.84; H, 4.15, N, 2.74.
In a typical experiment, to a round-bottomed flask
charged with substituted salicylaldehydes (1 mmol),
triphenyl phosphite (1.2 mmol), and aromatic amine
(1 mmol) in 5 mL of water, p-toluenesulfonic acid
(5 mol%) was added under stirring. The mixture was
stirred at room temperature for the appropriate time
(Table 2). After complete conversion, as indicated
by TLC, the mixture was quenched with H2O (20
mL ice-cold water) and extracted with ethyl acetate.
The organic layer was washed with brine and dried
over anhydrous sodium sulfate. The solvent was dis-
tilled on a Rota-evaporator under reduced pressure
to afford the crude products. The crude product was
purified by recrystallization from aqueous ethanol,
filtration, washed with cool water, and dried under in
vacuo.
Diphenyl(3-nitrophenyl amino)(2-hydroxyphenyl)
methyl Phosphonate (4d). Brown solid; 1H NMR
(400 MHz, DMSO-d6) δ: 5.80 (m, 1H, NH), 5.30
(d, JPH = 24.1 Hz, 1H, CHP), 6.76–7.69 (m, 18H,
ArH), 10.25 (s, 1H, OH); 13C NMR (100 MHz, DMSO-
d6) δ: 46.3 (d, JPC = 156.6 Hz), 106.2, 107.1, 109.9,
110.8,111.6, 114.9, 119.1, 120.1, 120.5, 122.8, 124.1,
125.3, 128.4, 129.4, 129.9, 148.7, 149.8, 150.1, 151.0,
155.3; IR (KBr) ν: 3412 (NH), 2927 (Ph OH), 1264
(P O), 1049 (P
O C); Found: C, 63.19; H, 4.33, N,
5.78. Calcd. for C25H21N2O6P (476.11); C, 63.03; H,
4.44, N, 5.88.
Diphenyl(4-chlorophenyl amino) (2-hydroxyphe-
nyl)methyl Phosphonate (4e). White solid; 1H NMR
(400 MHz, DMSO-d6) δ: 5.65 (dd, JPH = 25.1 Hz,
J = 9.2 Hz, 1H, CHP), 6.79–7.60 (m, 19H, ArH,
HN), 10.10 (s, 1H, OH); 13C NMR (100 MHz, DMSO-
d6) δ: 46.3 (d, JPC = 161.8 Hz), 114.6, 115.0, 119.2,
119.3, 120.1, 120.2, 120.6, 120.7, 121.3, 125.1, 125.3,
128.6, 129.7, 129.8, 145.9, 149.9, 150.0, 155.2; IR
(KBr) ν: 3416 (NH), 3219 (Ph OH), 1284 (P O),
Diphenyl(2-hydroxyphenyl)(phenylamino)methyl
Phosphonate (1a). White solid; 1H NMR (400 MHz,
DMSO-d6) δ: 5.67 (dd, JPH = 25.3 Hz, J = 8 Hz, 1H,
3
CHP), 5.25 (d, JPH = 8 Hz, 1H, NH), 6.57–7.51 (m,
19H, ArH), 10.05 (s, 1H, OH); 13C NMR (100 MHz,
DMSO-d6) δ: 46.2 (d, JPC = 161 Hz), 113.2, 114.9,
117.3, 119.2, 120.1, 120.2, 120.6, 120.7, 121.7, 125.1,
125.2, 128.9, 129.7, 129.8, 147.1, 150.1, 150.2, 155.3;
IR (KBr) ν: 3421 (NH), 3234 (Ph OH), 1246 (P O),
1071 (P
O C); Found: C, 64.29; H, 4.43, N, 3.18.
Calcd. for C25H21ClNO4P (465.09); C, 64.45; H, 4.54,
N, 3.01.
1178 (P
O C); Found: C, 60.59; H, 5.33, N, 3.15.
Calcd. for C25H22NO4P (431.13); C, 69.60; H, 5.14,
N, 3.25.
Diphenyl(2,5-dichlorophenyl amino)(2-hydroxy-
phenyl)methyl Phosphonate (4f). White solid; 1H
Diphenyl(2-hydroxyphenyl)(2-methylphenylami-
no)methyl Phosphonate (1b). Light yellow solid;
1H NMR (400 MHz, DMSO-d6) δ: 2.18 (s, 3H, CH3);
5.69 (dd, JPH = 25.4 Hz, J = 8 Hz, 1H, CHP), 5.23
(br, 1H, NH), 6.62–7.64 (m, 18H, ArH), 10.17 (s,
1H, OH); 13C NMR (100 MHz, DMSO-d6) δ: 17.3,
48.1 (d, JPC = 160.7 Hz), 111.1, 115.2, 118.1, 120.1,
120.2, 120.5, 120.6, 121.3, 123.6, 125.1, 125.3, 126.8,
129.4, 129.7, 129.8, 130.1, 144.3, 150.2, 150.3, 155.4;
IR (KBr) ν: 3442 (NH), 3063 (Ph OH), 1206 (P O),
NMR (400 MHz, DMSO-d6) δ: 5.83 (dd, JPH
=
23.8 Hz, J = 12 Hz, 1H, CHP), 6.13 (m, 1H,
NH), 6.73–7.56 (m, 17H, ArH), 10.38 (s, 1H, OH);
13C NMR (100 MHz, DMSO-d6) δ: 49.2 (d, JPC
=
158.5 Hz), 112.4, 115.6, 117.7, 118.2, 119.4, 119.8,
120.1, 120.14, 120.4, 125.3, 125.4, 129.8, 129.9,
130.4, 132.7, 143.0,149.8, 149.9, 155.7; IR (KBr)
ν: 3425 (NH), 3255 (Ph OH), 1247(P O), 1097
(P
O C); Found: C, 60.09; H, 4.13, N, 2.88. Calcd.
for C25H20Cl2NO4P (499.05); C, 60.02; H, 4.03, N,
2.80.
1069(P
O C); Found: C, 70.19; H, 5.33, N, 3.18.
Calcd. for C26H24NO4P (445.14); C, 70.10; H, 5.43,
N, 3.14.
Diphenyl(p-tolyl amino)(2-hydroxyphenyl)methyl
Phosphonate (4g). White solid; 1H NMR (400 MHz,
DMSO-d6) δ: 2.09 (s, 3H, CH3), 5.23 (d, JPH = 24.7 Hz,
1H, CHP), 5.63 (d, J = 9 Hz, 1H, NH), 6.61–7.60 (m,
18H, ArH), 10.01 (s, 1H, OH); 13C NMR (100 MHz,
DMSO-d6) δ: 20.0, 46.8 (d, JPC = 156.1 Hz), 113.3,
114.9, 118.9, 120.2, 120.5, 120.7, 121.8, 123.7, 124.0,
Diphenyl(4-bromophenyl amino)(2-hydroxyphe-
nyl)methyl Phosphonate (1c). White solid; 1H NMR
(400 MHz, DMSO-d6) δ: 5.63 (dd, JPH = 24.7 Hz, J =
8 Hz, 1H, CHP), 5.22(d, J = 10 Hz, 1H, NH), 6.67–
7.61 (m, 18H, ArH), 10.12 (s, 1H, OH); 13C NMR
Heteroatom Chemistry DOI 10.1002/hc

114 Wu et al.
125.2, 125.8, 128.1, 129.3, 129.6, 144.8,150.1, 151.1,
155.2; IR (KBr) ν: 3416 (NH), 3228 (Ph OH), 1242
118.4, 120.1, 120.4, 124.2, 124.3, 125.2, 126.7, 129.3,
129.8, 130.2, 131.5, 131.8, 144.2, 150.2, 150.3, 154.7;
IR (KBr) ν: 3444 (NH), 3244 (Ph OH), 1206 (P O),
1058 (P O- C); Found: C, 59.57; H, 4.53, N, 2.80.
Calcd. for C26H23BrNO4P (523.05); C, 59.56; H, 4.42,
N, 2.67.
(P O), 1077 (P
O C); Found: C, 70.09; H, 5.43, N,
3.18. Calcd. for C26H24NO4P (445.14); C, 70.10; H,
5.43, N, 3.14.
Diphenyl(2-methoxyphenyl
amino)(2-hydroxy-
phenyl)methyl Phosphonate (4h). Hazel solid; 1H
NMR (400 MHz, DMSO-d6) δ: 3.75 (s, 3H, OCH3),
5.38 (br, 1H, NH), 5.66 (d, JPH = 20 Hz, 1H, CHP),
6.67–7.40 (m, 18H, ArH), 10.14 (br, 1H, OH); 13C
NMR (100 MHz, DMSO-d6) δ: 47.2 (d, JPC = 157.5
Hz), 55.6, 110.2, 110.7, 115.3, 117.9, 119.3, 120.1,
120.5, 120.9, 121.2, 125.2, 125.4, 128.4, 128.5, 129.2,
129.7, 129.9, 135.4, 147.0, 149.9, 150.0, 155.5; IR
(KBr) ν: 3435 (NH), 2966 (Ph OH), 1226 (P O),
Diphenyl(p-tolyl amino)(2-hydroxy-5-nitrophe-
nyl)methyl Phosphonate (4l). Yellow solid; 1H NMR
(400 MHz, DMSO-d6) δ: 2.12 (s, 3H, Ar-CH3), 5.65
(d, JPH = 25.5 Hz, J = 8 Hz, 1H, CHP), 6.69–7.40
(m, 15H, ArH), 8.08 (d, J = 8 Hz, 1H, ArH), 8.60 (s,
1H, ArH), 11.83 (s, 1H, OH); 13C NMR (100 MHz,
DMSO-d6) δ: 20.0, 46.5 (d, JPC = 157.5 Hz), 113.4,
115.4, 120.0, 120.1, 120.5, 120.6, 123.7, 125.3, 125.4,
126.3, 129.4, 129.8, 129.9, 139.9, 144.2, 149.8, 149.9,
161.6; IR (KBr) ν: 3748 (NH), 3090 (Ph OH), 1187
1105 (P
O C); Found: C, 67.69; H, 5.33, N, 3.15.
Calcd. for C26H24NO5P (461.14); C, 67.67; H, 5.24,
N, 3.04.
(P O), 1099 (P
5.80. Calcd. for C26H23N2O6P (490.13); C, 63.67; H,
4.73, N, 5.71.
O C); Found: C, 63.58; H, 4.63, N,
Diphenyl(o-tolyl amino)(5-chloro-2-hydroxyphe-
1
nyl)methyl Phosphonate (4i). White solid; H NMR
SUPPORTING INFORMATION
(400 MHz, DMSO-d6) δ: 2.21 (s, 3H, Ar-CH3), 5.46
(br, 1H, NH), 5.63 (d, JPH = 24.3 Hz, J = 10 Hz,
1H, CHP), 6.67–7.40 (m, 17H, ArH), 10.52 (s, 1H,
Ph OH); 13C NMR (100 MHz, DMSO-d6) δ: 17.4,
48.1 (d, JPC = 160.7 Hz), 111.1, 115.2, 116.7, 118.4,
120.0, 120.4, 122.9, 123.8, 124.1, 125.2, 125.3, 126.7,
128.9, 129.4, 129.8, 130.2, 144.1, 149.9, 150.0, 154.3;
IR (KBr) ν: 3440 (NH), 3244 (Ph OH), 1270 (P O),
Supporting Information is available from the corre-
sponding author on request.
REFERENCES
[1] (a) Engel, R. Chem. Rev. 1977, 77, 349–367;
(b) Hiratake, J.; Oda, J. Biosci Biotechnol Biochem
1997, 61, 211–218; (c) Schug, K. A.; Lindner, W.
Chem Rev 2005 105, 67–113; (d) Moonen, K.; Lauryn,
I.; Stevens, C. V. Chem Rev 2004, 104, 6177–6215;
(e) Palacios, F.; Alonso, C.; Santos, J. M. Curr Org
Chem 2004, 8, 1481–1496.
1067 (P
O C); Found: C, 65.07; H, 4.73, N, 2.85.
Calcd. for C26H23ClNO4P (479.11); C, 65.07; H, 4.83;,
N, 2.92.
Diphenyl(2-methoxyphenyl amino)(5-chloro-2-
[2] (a) Vovk, A. I.; Mischenko, I. M.; Tanchuk, V. Y.;
Kachkovskii, G. A.; Sheiko, S. Y.; Kolodyazhnyi,
O. I.; Kukhar, V. P. Bioorg Med Chem Lett 2008, 18,
4620–4623; (b) Grembecka, J.; Mucha, A.; Cierpicki,
T.; Kafarski, P. J Med Chem 2003, 46, 2641–2655;
(c) Hirschmann, R.; Smith, A. B., III; Taylor,
C. M.; Benkovic, P. A.; Taylor, S. D.; Yagar, K. M.;
Sprengeler, P. A.; Benkovic, S. J. Science 1994,
265, 234–237; (d) Kafarski, P.; Lejczak, B. Phospho-
rus Sulfur Silicon Relat Elem 1991, 63, 193–215;
(e) Allen, M. C.; Fuher, W.; Tuck, B. J. Med Chem
1989, 32, 1652–1661; (f) Baylis, E. K.; Campbell,
C. D.; Dingwall, J. G. J Chem Soc, Perkin Trans 1
1984, 2845–2853; (g) Benkovic, S. J.; Hirschmann, R.
Tetrahedron Lett 1994, 35. 6853–6856; (h) Pan, W.;
Ansiaux, C.; Vincent, S. P. Tetrahedron Lett 2007, 48,
4353–4356; (i) Rao, X.; Song, Z.; He, L. Heteroatom
Chem 2008, 19, 512–516.
hydroxyphenyl)methyl Phosphonate (4j). Light
1
green solid; H NMR (400 MHz, DMSO-d6) δ: 3.85
(s, 3H, OCH3), 5.59 (br, 1H, NH), 5.66 (d, JPH
=
24.7 Hz, 1H, CHP), 6.66–7.47 (m, 17H, ArH), 10.51
(s, 1H, OH); 13C NMR (100 MHz, DMSO-d6) δ: 47.6
(d, JPC = 160.7 Hz), 55.6, 110.4, 110.9, 117.0, 118.2,
120.0, 120.4, 120.9, 122.8, 123.5, 125.3, 125.4, 128.2,
129.0, 129.8, 135.1, 147.2, 149.8, 149.9, 150.0, 154.6;
IR (KBr) ν: 3411 (NH), 2938 (Ph OH), 1226 (P O),
1070 (P
O C); Found: C, 62.87; H, 4.53, N, 2.85.
Calcd. for C26H23ClNO5P (495.10); C, 62.97; H, 4.46,
2.82.
Diphenyl(o-tolyl amino)(5-bromo-2-hydroxyphe-
nyl)methyl Phosphonate (4k). Lihgt green solid; 1H
NMR (400 MHz, DMSO-d6) δ: 2.21 (s, 3H, Ar-CH3),
5.47 (br, 1H, NH), 5.64 (dd, JPH = 24.3 Hz, J = 9
Hz, 1H, CHP), 6.63–7.93 (m, 17H, ArH), 10.58 (s,
1H, OH); 13C NMR (100 MHz, DMSO-d6) δ: 17.4,
48.1 (d, JPC = 160.3 Hz), 110.5, 111.2, 115.2, 117.3,
[3] (a) Saidi, M. R.; Azizi, N. Synlett 2002 1347–1349;
(b) Azizi, N.; Rajabi, F. M.; Saidi, R. Tetrahedron
Lett 2004, 45, 9233–9236; (c) Azizi, N.; Saidi, M. R.
Tetrahedron 2003, 59, 5329–5332; (d) Azizi, N.; Saidi,
M. R. Eur J Org Chem 2003, 23, 4630–4633.
[4] Ranu, B. C.; Hajra, A.; Jana, U. Org Lett 1999, 1,
1141–1143.
Heteroatom Chemistry DOI 10.1002/hc

Convenient One-Pot Synthesis of α-Amino Phosphonates in Water Using p-Toluenesulfonic Acid 115
[5] Chang, Q.; Huang, T. J. Org Chem 1998, 63, 4125–
[14] Lee, S. G.; Park, J. H.; Kang, J.; Lee, J. K. Chem Com-
mun 2001, 1698–1699.
4128.
[6] Chandrasekhar, S.; Prakash, S. J.; Jagadeshwar, V.
Tetrahedron Lett 2001, 42, 5561–5563.
[7] Tajbakhsh, M.; Heydari, A.; Alinezhad, H.; Ghanei,
M.; Khaksr, S. Synthesis 2008, 352–354.
[8] Kaboudin, B.; Nazari, R. Tetrahedron Lett 2001, 42,
8211–8213.
[9] Mitragotri, S. D.; Pore, D. M.; Desai, U. V.;
Wadgaonkar, P. P. Catal Commun 2008, 1822–
1826.
[10] Manabe, K. K.; Obayashi, S. Chem Commun 2000,
669–670.
[11] Ha, H.; Nam, J. Synth Commun 1992, 22, 1143–1148.
[12] Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Synthesis
2004, 2692–2696.
[15] Xu, F.; Luo, Y.; Deng, M.; Shen, Q. Eur J Org Chem
2003, 4728–4730.
[16] Manjula, A.; Rao, B.; Neelakantan, P. Synth Commun
2003, 33, 2963–2969.
[17] Firouzabadi, H.; Jafarpour, M.J. Iran Chem Soc 2008,
5, 159–183.
[18] Hosseini-Sarvari, M. Tetrahedron 2008, 61, 5459–
5466.
[19] Manabe, K.; Kobayashi, S. Chem Commun 2000,
669–670.
[20] Ando, K.; Egami, T. Heteroatom Chem 2011, 22, 358–
362.
[21] Mandhane, P. G.; Joshi, R. S.; Nagargoje, D. R.; Gill,
C. H. Chin Chem Lett 2011, 22, 563–566.
[22] Wang, B.; Miao, Z. W.; Huang, Y.; Chen, R. Y. Het-
eroatom Chem 2007, 18, 65–69.
[13] Bhagat, S.; Chakraborti, A. K. J Org Chem 2007, 72,
1263–1270.
Heteroatom Chemistry DOI 10.1002/hc