Silica sulfuric acid as a recyclable catalyst for a one-pot synthesis of α-aminophosphonates in solvent-free conditions

Article abstract of DOI:10.2174/157017809789124830

A simple and efficient method has been developed for the synthesis of a-aminophosphonates by a one-pot three-component condensation of aldehydes, amines and diethyl phosphite in the presence of a catalytic amount of silica sulfuric acid under solvent-free reaction conditions. The major advantages of the present method are good yields, inexpensive, ecofriendly and reusable catalyst, short reaction times, mild and solvent-free reaction conditions.

Full text of DOI:10.2174/157017809789124830

470
Letters in Organic Chemistry, 2009, 6, 470-473
Silica Sulfuric Acid as a Recyclable Catalyst for a One-Pot Synthesis of
ꢀ-Aminophosphonates in Solvent-Free Conditions
Jing-Jun Yang, Jin-Ning Dang, Yu-Wei Chang*
Department of Chemistry, Gansu Normal University for Nationalities, Hezuo,Gansu 747000, P.R. China
Received April 28, 2009: Revised June 25, 2009: Accepted June 25, 2009
Abstract: A simple and efficient method has been developed for the synthesis of ꢀ-aminophosphonates by a one-pot
three-component condensation of aldehydes, amines and diethyl phosphite in the presence of a catalytic amount of silica
sulfuric acid under solvent-free reaction conditions. The major advantages of the present method are good yields,
inexpensive, ecofriendly and reusable catalyst, short reaction times, mild and solvent-free reaction conditions.
Keywords: ꢀ-Aminophosphonates, aldehydes, amines, alkyl phosphite, three-component reaction.
INTRODUCTION
associated with this cheap and nonhazardous catalyst, we
considered silica sulfuric acid to be an ideal heterogeneous
acid catalyst for the synthesis of ꢀ-aminophosphonates.
ꢀ-Aminophosphonates and other related derivatives have
been valuably involved in the preparation of medicinal
compounds and synthetic intermediates [1]. The utilities of
ꢀ-aminophosphonates as peptide mimics [2], haptens of
catalytic antibodies [3], antibiotics and pharmacological
agents [4], and herbicides [5] have been reported. Hence,
greater attentions has been attracted to these compounds due
to their wide biological activity.
O
O
SiO2
OH
Cl
S
OH
+
SiO2
O
S
OH
O
O
Scheme 1.
Also, it is widely reported in the literature [10] that
application of microwave (MW) irradiation enables
realization of reactions, otherwise requiring harsh conditions
and too slow for practical purposes. Moreover, MW assisted
reactions are believed to satisfy the demands of ‘green
chemistry’ allowing for solvent-free conditions to be
employed.
Recently many synthetic methods for ꢀ-aminophos-
phonates have been reported. Among these, the classical
method is the nucleophilic addition of phosphites with
imines, that was one of the most preferred methods in the
presence of Lewis acids [6] SnCl2, SnCl4, BF3.Et2O, ZnCl2,
MgBr2, and InCl3. However, these reactions cannot proceed
in one-pot manner from a carbonyl compound, an amine, and
a phosphite because the water generated during the course of
the reaction can decompose or deactivate the Lewis acid [7].
Although three-component ꢀ-aminophosphonate syntheses
starting from aldehydes, amines, and diethyl phophite or
triethyl phosphite catalyzed by Lewis acids [8] have been
reported, these new developments also suffer from
stoichiometric amount of catalysts, expensive reagents,
longer reaction times, and use of harmful organic solvents.
Hence, there is still a need to develop a more efficient,
practical, and environmentally benign method for the
synthesis of ꢀ-aminophosphonic esters.
Herein, we report an efficient, practical, and high
yielding method for a three-component, one-pot synthesis of
ꢀ-aminophosphonic esters using silica sulfuric acid under
solvent-free reaction conditions.
RESULTS AND DISCUSSION
An initial study was conducted by the treatment of
benzaldehyde (1), aniline (2), and diethyl phosphite in
methanol in the presence of a catalytic amount of silica
sulfuric acid [11] (20 mol%) and irradiating with MWs for 3
min to afford the corresponding aminophosphonate 3a in 85
% yield. Under these conditions, we attempted to prolong
reaction time to improve the yield, but no relevant effect has
not been observed (Entry 2 in Table 1). It is exciting that the
removing of methanol as solvent can wonderfully improve
the yield (94%) (Entry 5 in Table 1). Rise in MW power has
not led to better yield in 3 min. When water was used as
solvent, although all of the substrates did not dissolve well in
it, the yield has not been remarkably decreased (Entry 3 in
Table 1). After that, the amount of the catalyst was
optimized. It was found that, under solvent-free conditions,
silica sulfuric acid can effectively catalyze ꢀ-
aminophosphonate formation under MW irradiation. The
above results are summarized in Table 1.
Recently, the use of solid acidic catalysts in organic
synthesis has attracted much attention since they possess
many advantages, for example operational simplicity,
nontoxicity, recyclability, low cost, and ease of isolation
after completion of the reaction. Silica sulfuric acid has
emerged as a powerful solid acidic catalyst in synthetic
methodology [9]. The silica sulfuric acid could easily be
prepared by the reaction of silica gel and chlorosulfonic acid
(Scheme 1) [9b]. Owing to the numerous advantages
*Address correspondence to this author at the Department of Chemistry,
Gansu Normal University for Nationalities, Hezuo, Gansu 747000, P. R.
China Tel: +86 (941) 8252686; Email: changyuwei@hzmtc.edu.cn
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

Silica Sulfuric Acid as a Recyclable Catalyst for a One-Pot
Letters in Organic Chemistry, 2009, Vol. 6, No. 6
471
Table 1. Synthesis of ꢀ-Aminophosphonate 3a under Different Conditionsa
O
H
O
O
P
Silica sulfuric acid
MW
OEt
OEt
N
P
OEt
Ph NH2
+
+
Ph
Ph
H
H
OEt
Ph
3a
1
2
Entry
Solvent
Amount of Catalyst (mol %)
Time (min)
Yields (%)b
1
2
Methanol
Methanol
Water
20
20
20
20
20
20
20
20
10
3
5
3
2
3
5
3
3
3
85
86
90
88
94
93
83
90
85
3
4
No solvent
No solvent
No solvent
No solvent
No solvent
No solvent
5
6
7 c
8 d
9
aAll the reactions were performed on aldehyde 1 (1 mmol), amine 2 (1 mmol) and diethyl phosphite (1 mmol) in the presence of silica sulfuric acid (20 mol%) for 3 min under MW
irradiation (power 1000 W) unless otherwise specified.
bIsolated yield.
cMW irradiation power 1200 W.
d MW irradiation power 800 W.
Table 2. Synthesis of ꢀ-Aminophosphonates Catalyzed by Silica Sulfuric Acida
O
O
O
P
H
Silica sulfuric acid
MW
OEt
OEt
N
P
OEt
R1 NH2
+
+
R1
R
H
H
OEt
R
Yieldsb
R
R1
Entry
Product
Time (min)
1
3a
3b
3c
3d
3e
3
94
2
3
4
5
O2N
Me
2
2
5
3
96
93
97
94
MeO
MeO
O2N
6
7
3f
4
4
85
97
OH
MeO
MeO
3g

472 Letters in Organic Chemistry, 2009, Vol. 6, No. 6
Yang et al.
(Table 2). Contd…..
Yieldsb
R
R1
Entry
Product
3h
Time (min)
8
9
3
89
96
3i
3j
3
5
MeO
MeO
OMe
10
88
Me
11
12
3k
3l
4
5
79
97
Me
MeO
O
Me
O
O
13
3m
4
91
Me
OH
Me
aReaction conditions: aldehyde (1 mmol), amine (1 mmol), diethyl phosphite (1 mmol), silica sulfuric acid (20 mol%), 1000 W.
bIsolated yield.
Table 3. The Investigation of Recovering and recycling the
Catalysta
Encouraged by the remarkable results obtained with the
above reaction conditions, and in order to show the
generality and scope of this new protocol, we used a variety
of aldehydes and amines, which were subjected to the one-
pot three-component operation in the presence of a catalytic
amount of silica sulfuric acid to furnish the corresponding ꢀ-
aminophosphonates in moderate to high yields [12]. The
results are summarized in Table 2. Table 2 demonstrates that
there were not obvious electronic effects from differently
substituted aromatic aldehydes. Benzaldehydes with both
electron-donating and -withdrawing groups could be
accomplished the one-pot reaction. The reaction was
compatible with various substitutents such as OMe, NO2 and
Me. Lower yields were observed for aliphatic aldehydes,
including cinnamaldehyde (Entries 8 and 11 in Table 2).
Morever, no conjugate addition product was obtained for
cinnamaldehyde (Entry 8 in Table 2). When anilines with
electron-withdrawing substituents were used, the reactions
needed to be carried out for longer periods (Entry 4 in Table
2). In the case of aliphatic amines, such as benzylamine, the
corresponding ꢀ-aminophosphonates were obtained in good
yields (Entry 9 in Table 2). In order to estimate the
efficiency of this catalyst system, an amino acid was used as
starting product under the selected conditions (Entry 13 in
Table 2): the reaction proceeded smoothly, and the yield was
good.
Run
Yieldb (%)
Recovery of catalyst (%)
1
2
3
4
94
94
93
94
99
98
98
97
aReaction conditions: aldehyde(1) (1 mmol), amine (2) (1 mmol), diethyl phosphite (1
mmol), silica sulfuric acid (20 mol%), 1000 W.
bIsolated yield.
In conclusion, silica sulfuric acid was found to be an
efficient catalyst for the one-pot reaction of aldehydes,
amines,
and
diethyl
phosphite
to
obtain
ꢀ-
aminophosphonates in good to excellent yields. With the
increasing need of green synthetic procedures, the
advantages such as high yields, solvent-free condition, and
ease of product isolation make the present methodology
environmentally benign.
ACKNOWLEDGEMENT
The financial support from Gansu Normal University for
Nationalities is gratefully acknowledged.
The ability to recover and recycle silica sulfuric acid and
its catalytic activity was studied (Table 3). The catalyst can
be easily separated by addition of CH2Cl2 and filtration.
Thus, the recovery and recycle of silica sulfuric acid could
be very convenient. The reaction of benzaldehyde
(1), aniline (2), and diethyl phosphite, under the present
reaction conditions reported in Table 3, furnished the
ꢀ-aminophosphonates in good yields over four cycles.
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