Cd(ClO4)2·xH2O as a novel catalyst for the synthesis of α-aminophosphonates under solvent-free conditions

Article abstract of DOI:10.1016/j.catcom.2011.10.025

In this paper, we report cadmium perchlorate hydrate to be an novel, expeditious catalyst for the three-component one-pot reaction of an amine, an aldehyde and a H-phosphonate diesters in open air without any solvent, leads to α-aminophosphonates in excellent yields. To the best of our knowledge this finding is the first example of a cadmium perchlorate hydrate catalyzed Kabachnik-Fields reaction.

Full text of DOI:10.1016/j.catcom.2011.10.025

Catalysis Communications 17 (2012) 114–117
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Catalysis Communications
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Short Communication
Cd(ClO4)2∙xH2O as a novel catalyst for the synthesis of α-aminophosphonates under
solvent-free conditions
⁎
Someshwar D. Dindulkar, Mudumala Veeranarayana Reddy, Yeon Tae Jeong
Department of Image Science and Engineering, Pukyong National University, Busan, Republic of Korea, 608-737
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 July 2011
Received in revised form 19 October 2011
Accepted 23 October 2011
Available online 30 October 2011
In this paper, we report cadmium perchlorate hydrate to be an novel, expeditious catalyst for the three-
component one-pot reaction of an amine, an aldehyde and a H-phosphonate diesters in open air without
any solvent, leads to α-aminophosphonates in excellent yields. To the best of our knowledge this finding is
the first example of a cadmium perchlorate hydrate catalyzed Kabachnik-Fields reaction.
© 2011 Elsevier B.V. All rights reserved.
Keywords:
Cd(ClO4)2∙xH2O
One-pot reaction
α-aminophosphonates
Solvent-free conditions
1. Introduction
have been reported as an effective catalyst for the synthesis of α-
aminophosphonates without any activator or base [22].
Phosphorus compounds constitute an important class of organic
compounds with diverse biological activities and possess a wide
range of application [1], owing to their biological and physical proper-
ties as well as their utility as synthetic intermediates [2–6]. The activ-
ity of α-aminophosphonates as antibiotics, antitumor agents,
pharmacogenic agents and herbicidal is reported in literature
In this paper, we report the use of Cd(ClO4)2∙xH2O as a novel, effi-
cient catalyst for the preparation of α-aminophosphonates via a
three-component system, composing of aldehydes/ketones, amines,
and dimethylphosphite/diethylphosphite under solvent-free condi-
tion (Scheme 1). We eventually achieved excellent yields in very
short duration at milder condition. Solvent-free reaction condition
has been demonstrated to be an efficient technique for various organ-
ic reactions. It often leads to a remarkable decrease in reaction time,
increased yields, easier workup procedure. Our model of studies indi-
cated that this reaction proceeds with catalytic amount of catalyst
with short reaction time (20 to 55 min) and easy work up procedure
are the some of the advantages of this protocol.
[7–11].
A more detailed discussion of the mechanism of the
Kabachnik-Fields reaction, its synthetic potential and the biological
activity of the α-aminophosphonates was well documented [12].
There are many report available using addition of phosphorous
nucleophiles to imines is a general synthetic method for the prepara-
tion of α-aminophosphonates via two steps [13–16]. Catalytic syn-
thetic methods attract
a
special attention because they play
In search for an effective catalyst and the best operative experi-
mental conditions, we have selected 4-chlorobenzaldehyde, 4-
nitroaniline as an electron-deficient amine and dimethylphosphite.
For this model reaction, we have tested various acids and metal cata-
lysts. The best results were obtained in using 5 mol% of Cd(ClO4)2∙-
xH2O at rt for 2 h (yields 94%) and at 40 °C for 20 min (96%) under
neat conditions (Table 1).
impressive role in many organic reaction. Over the last few years
we observed there are many acid catalysts were used in synthetic or-
ganophosphorus chemistry. Typically Bronsted acid or Lewis acids
like In(OTf)3, ZnCl2, CdI2/benzene, CdI2/microwave have been used
[17–21]. Some loss of advantage of these reported catalyst because
of their long reaction time, comparative more tedious work up purifi-
cation procedure and most of the reported methods require strictly
anhydrous conditions. Very recently Zirconium(IV) Compounds
2. Experimental
2.1. General
Solvents were purified by conventional methods and distilled
under nitrogen, prior to use. Dimethylphosphite/diethylphosphite
and Cd(ClO4)2∙xH2O were obtained from Aldrich. The progress of
the reactions was monitored by thin layer chromatography (TLC) on
⁎
Corresponding author at: Department of Image Science and Engineering, Pukyong
National University, Busan, Republic of Korea. Tel.: +82 51 6296411; fax: +82 51
6296408.
E-mail address: ytjeong@pknu.ac.kr (Y.T. Jeong).
1566-7367/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2011.10.025

S.D. Dindulkar et al. / Catalysis Communications 17 (2012) 114–117
115
Scheme 1. Cd(ClO4)2∙xH2O catalyzed synthesis of α-aminophosphonates.
250 μm silica plates using 8:2 n-hexane and ethyl acetate mixture as
an eluent. All the 1H and 13 C NMR spectra of the synthesized com-
pounds were recorded on Jeol JNM ECP 400 NMR spectrometer at
294 K. The 1H and 13 C NMR spectra were measured respectively
0.03 M and 0.05 M solutions in CDCl3 with TMS as internal reference
in 5 mm NMR tubes. The 1H and 13 C chemical shift values are given
in δ scale (ppm) and referred to TMS, (13 C, via the solvent signal of
CHCl3 at 77.16 ppm). Coupling constants J are reported in Hz.
crude solid was recrystallized in the mixture of chloroform and hex-
ane to afford the pure product without further column purification.
3. Results and discussion
In order to explore the scope and the limitations of this novel meth-
od, we investigated the reaction using several electron-donating meth-
oxy, ethoxy, hydroxy and isopropyl and electron-withdrawing nitro,
bromo and chloro substituted benzaldehydes as well as amine with
H-dialkylphosphonate HP(O)(OR1)2 (R1: Me, Et) under solvent-free
conditions at 40 °C (Table 2). It was observed that, excellent yields
were obtained with electron withdrawing substituent on aromatic
benzaldehyde and aromatic amine. The reaction was compatible with
various functional groups such as Cl, Br, F, OMe, OEt, NO2, OH, do not in-
terfere by competitive complex formation with the catalyst.
The reaction of 4-chlorobenzaldehyde, 4-nitroaniline and dimethyl
phosphite in presence of different catalyst was considered as the
model reaction. In our present study we screened different catalyst
and condition. Surprisingly, the best result obtained in using 5 mol%
Cd(ClO4)2 ∙xH2O at room temperature in 2 h, afforded a high yield of
2.2. General procedure for the preparation of α-aminophosphonates
using Cd(ClO4)2∙xH2O
In a typical experiment, to a mixture of aldehyde (1 mmol), amine
(1 mmol), and dimethylphosphite/diethylphosphite (1.2 mmol) was
added Cd(ClO4)2∙xH2O (5.0 mol%) and stirred at room temperature
to 40 °C for the appropriate reaction time. The progress of the reac-
tion was monitored by TLC. When the reaction was completed, plenty
of water was added to the reaction mixture then filtered and washed
with hexane in order to get the solid crude product. And obtained
Table 1
Effect of various catalysts and solvent condition on the synthesis of α-aminophosphonates 13a.
NO2
O
H2N
O
H
HN
+
+
HP(OMe)2
P(OMe)2
O
Cl
NO2
Cl
Entry
Catalyst (5 mol%)
Solvent
Temp (°C)
Time (h)
Yieldb(%)
1
2
3
4
5
6
7
8
Cu-Sn (200 mesh)
Cu-Sn (200 mesh)
Amberlite-IR-15
Amberlite-IR-15
ZnCl2 SiO2
ZnCl2 SiO2
ZnCl2 SiO2
MgCl2·4H2O
MgCl2·4H2O
Cd(ClO4)2∙xH2O
Cd(ClO4)2∙xH2O
Cd(ClO4)2∙xH2O
Cd(ClO4)2∙xH2O
Cd(ClO4)2∙xH2O
Cd(ClO4)2∙xH2O
Cd(ClO4)2∙xH2O
Cd(ClO4)2∙xH2O
Cd(ClO4)2∙xH2O
Cd(ClO4)2∙xH2O (10 mol%)
Cd(ClO4)2∙xH2O (20 mol%)
Toluene
Neat
Toluene
neat
MeCN
neat
neat
90
90
90
90
80
80
80
80
80
rt
80
rt
80
100
100
rt
12
4
24
7
5
5
1
3
1
5
2
6
3
4
4
2
65
85
70
75
60
73
78
52
74
78
84
70
82
78
75
94
96
96
97
97
MeCN
neat
9
10
11
12
13
14
15
16
17
18
19
20
MeCN
MeCN
EtOH
EtOH
H2O
PEG-400
neat
neat
40
60
40
40
20 min
20 min
20 min
20 min
neat
neat
neat
a
4-Chlorobenzaldehyde (1 mmol) was treated with 4-nitroaniline (1 mmol) and Dimethyl phosphite (1.2 mmol) in the presence of the catalyst 5 mol% (except entry 19, 20)
under solvent-free conditions (except entry 1, 3, 5, 8, 10, 11, 12, 13, 14, and 15).
b
Isolated yields.

116
S.D. Dindulkar et al. / Catalysis Communications 17 (2012) 114–117
Table 2
when Cd(ClO4)2∙xH2O was used under solvent condition. We observed
reaction proceeding with high yield in less time when diethyl phosphite
used as nucleophile in place of dimethyl phosphite nucleophile. In
terms of catalyst loading, 5 mol% was sufficient and mandatory for com-
pletion of reaction. However no significant improvement was observed
with 10 or 20 mol% of Cd(ClO4)2∙xH2O. Once, the reaction conditions
were optimized using Cd(ClO4)2∙xH2O, a variety of aromatic/aliphatic
aldehydes as well as aliphatic ketone and different substituted anilines,
were coupled with HP(O)(OMe)2/ HP(O)(OEt)2 and substituted ani-
lines to produce desired product.
Therefore, the advantages of our present methodology using of
Cd(ClO4)2∙xH2O include: (i) use of solvent free condition (ii) anhy-
drous condition need not to be maintained (iii) no base or any addi-
tional activator as well as additive required. However, there is not a
single report on the use of cadmium perchlorate hydrate as a catalyst
for the synthesis of α-aminophosphonates. All the compounds are
well reported which were further characterized by their spectral
techniques (1H and 13 C NMR) and synthesized compounds are in
good agreement with the literature compounds, which were further
provided as supplementary information.
Synthesis of diversified α-aminophosphonates derivatives in presence of 5 mol% Cd
(ClO4)2∙xH2O via Scheme 1.
Entrya
Aldehyde/Ketone
R1
R2
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
R=H
R=H
R=4-MeO
R=4-MeO
R=4-EtO
R=4-EtO
R=4-OH
R=4-OH
R=4-OH
R=4-OH
R=4-Cl
R=4-Cl
R=4-Cl
R=4-Cl
R=4-Cl
R=4-Br
R=4-Br
R=4-iso-Pr
R=4-NO2
Cylohexanone
2-Pentanone
Butyraldehyde
Butyraldehyde
Butyraldehyde
Cyclohexanecarboxaldehyde
Isobutyraldehyde
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
H
4-NO2
4-F
4-Br
NO2
4-Br
4-Br
4-F
45
30
55
50
35
30
50
45
40
15
20
30
20
10
25
20
40
50
50
40
55
360
270
360
40
180
92
96
87
91
90
96
94
90
94
96
94
98
96
97
96
93
91
96
87
82
79
53
67
52
78
72
9
4-NO2
4-NO2
4-F
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Me
Me
Me
Et
4-Br
4-NO2
4-Br
4-NO2
4-Br
4-NO2
4-NO2
4-NO2
4-NO2
H
H
4-NO2
4-Cl
4-NO2
H
Et
Me
Me
Me
Me
Me
Me
Me
Me
Et
A plausible mechanism of the reaction has been proposed on the
basis of formation of a Schiff base as intermediate [23, 24], which
has been isolated and characterized by NMR spectroscopy. After for-
mation of Schiff base followed by the nucleophilic attack of phosphite
on imino carbon, subsequent shifting of hydrogen atom leads to the
formation of α-aminophosphonates (Scheme 2).
Me
Me
a
All reaction condition: aldehydes (1 mmol), amine (1 mmol), HP(O)(OMe)2/ HP
(O)(OEt)2 (1.2 mmol) and Cd(ClO4)2∙xH2O (5 mol%) at 40 °C.
4. Conclusion
b
Isolated yields.
In conclusion, we have developed a new method for the synthesis
of α-aminophosphonates by a three-component one-pot reaction
using commercially available Cd(ClO4)2∙xH2O as efficient catalyst.
This methodology using Cd(ClO4)2∙xH2O is simple, novel and highly
efficient catalyst, which afford α-aminophosphonates in good to ex-
cellent yields under mild and solvent free conditions. Cleaner conver-
sion, solvent-free, higher yields, very short duration, avoidance of the
tedious work-up procedure as well as the simplicity of operation are
some of the advantages of this protocol.
96% in 20 min at 40 °C. However, no improvement in the yield beyond
this duration and increase in amount of catalyst (see Table 1 entry
17). To see effect of solvent for improvement of yield we screen differ-
ent solvents such as MeCN, EtOH, PEG-400 and aqueous medium, it is
observed that under solvent condition required longer times (2–6 h)
to afford comparable yields. A careful analysis of Table 1 reveals the
fact that, the reaction afforded only 30–82 % yield in the presence of differ-
ent catalysts such as Y(O2CCH3)3·xH2O, Zn(O2CCH3)2∙2H2O, ZnCl2∙SiO2
and MgCl2·4H2O. It is interesting to report that with use of Y(O2CCH3)3·
xH2O and Zn(O2CCH3)2·2H2O conversion rate of intermediate imine to
product is very poor in neat as well as under solvent condition. When
ZnCl2 SiO2 heterogeneous catalyst and MgCl2·4H2O used as catalyst
under neat condition, they showed good improvement in the yield of re-
action, but promising results were obtained with Cd(ClO4)2∙xH2O in lesser
time with better yield.
Acknowledgements
This research work was supported by the Industrial Technology
Development Program, which was conducted by the Ministry of
Knowledge Economy of the Korean Government.
Appendix A. Supplementary data
In order to elucidate the role of Cd(ClO4)2∙xH2O, a controlled reac-
tion was carried out with Cd(ClO4)2∙xH2O with different mole, temper-
ature and solvent condition. Reaction takes long time to complete,
Supplementary data to this article can be found online at doi:10.
1016/j.catcom.2011.10.025.
Scheme 2. Postulated mechanism for the one-pot synthesis of α-aminophosphonates promoted by Cd(ClO4)2∙xH2O.

S.D. Dindulkar et al. / Catalysis Communications 17 (2012) 114–117
117
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