A sulfonic acid functionalized ionic liquid as a homogeneous and recyclable catalyst for the one-pot synthesis of α-aminophosphonates

Article abstract of DOI:10.1016/j.tetlet.2009.05.020

A sulfonic acid functionalized ionic liquid is used as a Br?nsted acid catalyst for the one-pot, three-component synthesis of α-aminophosphonates from aldehydes and ketones at room temperature in water. This homogeneous catalytic procedure is simple and e

Full text of DOI:10.1016/j.tetlet.2009.05.020

Tetrahedron Letters 50 (2009) 4236–4238
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A sulfonic acid functionalized ionic liquid as a homogeneous and
recyclable catalyst for the one-pot synthesis of a-aminophosphonates
*
Jafar Akbari, Akbar Heydari
Chemistry Department, Tarbiat Modares University, PO Box 14155-4838, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A sulfonic acid functionalized ionic liquid is used as a Brønsted acid catalyst for the one-pot, three-com-
ponent synthesis of -aminophosphonates from aldehydes and ketones at room temperature in water.
This homogeneous catalytic procedure is simple and efficient and the catalyst can be reused at least
six times without any noticeable decrease in catalytic activity.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 13 March 2009
Revised 25 April 2009
Accepted 8 May 2009
Available online 13 May 2009
a
Keywords:
Homogeneous catalysis
Functionalized ionic liquid
a-Aminophosphonates
Recycling
a
-Aminophosphonates are important compounds from a bio-
their ease of recovery and reuse, which makes them viable
alternatives to volatile organic solvents.27,28 Combining the useful
characteristics of solid acids and mineral acids, Brønsted-acidic
task-specific ionic liquids (TSILs) have been synthesized to replace
traditional mineral liquid acids, such as hydrochloric acid and sul-
furic acid in chemical reactions.29 Such acidic TSILs play dual roles
as solvent and catalyst in organic reactions.30–33 The use of
Brønsted-acidic TSILs as catalysts is an area of ongoing activity
and it is expected that these TSILs may further expand the applica-
tion of ILs in chemistry.
logical point of view. It is known that they can act as peptide
mimetics,1 enzyme inhibitors,2 and antibiotic and pharmacological
agents,3,4 and as herbicides, fungicides, insecticides5 and plant
growth regulators.6 Substantial progress has been made towards
the development of efficient methods for the preparation of these
compounds.7–9 Although many methods have been developed for
hydrophosphonylation of imines, they suffer from drawbacks such
as the use of expensive and hazardous phosphorus sources, high
temperatures, multistep synthesis, stoichiometric amounts of cat-
alyst and low product selectivities and yields. Recently, nucleo-
philic addition of phosphite to imines, catalyzed by an acid or a
base, has emerged as an important alternative for the synthesis
In continuation of our interest in ionic liquid mediated organic
reactions, we have explored the utility of a task-specific ionic
liquid as a catalyst for the reaction between various aldehydes or
ketones, amines and trimethyl phosphite to afford the correspond-
of a
-aminophosphonates.10–20 Typically, Lewis acids such as SnCl4,
ZnCl2, SnCl2, BF3ÁOEt2, MgBr2 and InCl3 have been used as cata-
lysts21,22 for this process. However, these reactions could not be
carried out efficiently in a single step with carbonyl, amine and
phosphite functionalities because amines and the water formed
during imine formation can decompose or deactivate these Lewis
acids.23 In previous reports, we have shown that Brønsted acids
such as heteropoly acid, guanidine hydrochloride and supported
ing a-aminophosphonates (Scheme 1). The synthesis of the ionic li-
quid was carried out using a method similar to that reported.34 To
the best of our knowledge, this is the first report of a functionalized
ionic liquid catalyzed synthesis of
a-aminophosphonates.
O
R3
R1
oxalic acid catalyzed the synthesis of
a
-aminophosphonates.24–26
R2
O
NH
MeO
OMe
TSIL(10 mol%)
H2O
1
P
P
However, there is a need to develop one-pot syntheses of
phosphonates using water-tolerant catalysts.
a-amino-
R1
+
OMe
OMe
R2
OMe
R3NH2
4
In recent years, ionic liquids have emerged as useful alterna-
tives to conventional organic solvents due to their specific proper-
ties, such as wide liquid range, negligible vapor pressure, as well as
3
2
+
_
TSIL
N
N
SO3H
CF3SO3
* Corresponding author. Fax: +98 21 82883455.
E-mail address: akbar.heydari@gmx.de (A. Heydari).
Scheme 1. Three-component reaction catalyzed by a TSIL.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.05.020

J. Akbari, A. Heydari / Tetrahedron Letters 50 (2009) 4236–4238
4237
The reaction of trimethyl phosphite with the imine generated
in situ from benzaldehyde and aniline at room temperature in
the presence of 5 mol % of the sulfonic acid functionalized ionic li-
+
+
H
H
Ph
H
O
N
NH2
quid afforded the corresponding a-aminophosphonate in 98% yield
H
+
P(OMe)3
(Table 1, entry g). The reaction was complete in 10 min at room
temperature and the product was isolated in high purity by filtra-
tion. In order to examine the scope of this process, several aliphatic
and aromatic aldehydes were reacted under the optimized condi-
tions and the results are shown in Table 1. Both aromatic and ali-
phatic aldehydes reacted with aniline to form the corresponding a-
aminophosphonates. Importantly, aromatic aldehydes possessing
either electron-donating or electron-withdrawing substituents re-
+
- H2O
H2O
HN
Ph
MeOH
HN
Ph
_
OH
(OMe)
+
P
2
P
O
Me
O
MeO
OMe
acted efficiently giving excellent yields of the expected
a-amino-
phosphonates 4a,b,e,h,i. Encouraged by these results, we next
directed our studies towards a ketone and performed the reaction
under similar conditions. Reaction of 4-methoxyacetophenone
with aniline and trimethyl phosphite proceeded under mild condi-
Scheme 2. Proposed mechanism for the three-component reaction.
tions (room temperature, 1 h) to give the corresponding
a-amin-
ophosphonate 4l in excellent yield and high purity (Table 1,
entry l), despite the fact that the reactions of ketones and amines
has been repeatedly reported as challenging.35 It is important to
note that when benzaldehyde, aniline and trimethyl phosphite
were reacted in the absence of the ionic liquid, the reaction did
not proceed. The effect of solvent was also examined. Reaction in
the absence of water did not take place, but in the presence of
water (1 mL) the product formed rapidly.
The mechanism of this reaction is believed to involve formation
of an activated imine by the ionic liquid so that addition of the
phosphite is facilitated to give a phosphonium intermediate, which
then undergoes reaction with the water generated during forma-
Figure 1. Recycling of the TSIL catalyst. All reactions run for 10 min at rt.
tion of the imine to give the
a-aminophosphonate and methanol
phosphite (3 mmol) was added. After completion of the reaction,
as indicated by TLC, the ionic liquid was separated from the reac-
tion mixture by extraction with water. The products were sepa-
rated by filtration and vacuum dried. The products were
identified by NMR spectroscopy. Spectral data for selected prod-
ucts: Compound 4a: white solid, mp 60 °C; 1H NMR (500 MHz,
as shown in Scheme 2.36
The ionic liquid could be recycled after removing the products
and water. The reaction of benzaldehyde, aniline and trimethyl
phosphite gave the corresponding product in similar yields and
purities over six cycles (Fig. 1). The ionic liquid retained its struc-
ture as confirmed by NMR spectroscopy.
In summary, we have demonstrated that a readily available,
highly efficient, task-specific ionic liquid can be used as a recycla-
ble catalyst for the synthesis of
hydes and ketones in water.
CDCl3):
d 3.51 (m, 1H), 3.79 (d, J = 11.8 Hz, 3H), 3.83 (d,
J = 10.1 Hz, 3H), 5.20 (d, J = 24 Hz, 1H), 6.80–7.28 (m, 5H), 7.30
(d, J = 8.5 Hz, 2H), 7.50 (d, J = 8.5 Hz, 2H); 13C NMR (125 MHz,
2
2
a-aminophosphonates from alde-
CDCl3): d 56.1 (d, JP–C = 7.0 Hz, OCH3), 56.2 (d, JP–C = 6.8 Hz,
1
OCH3), 57.2 (d, JP–C = 150 Hz, CH), 114.3 (CH), 120.0 (CH), 128.2
(d, JP–C = 5.8 Hz, CH), 128.4 (d, JP–C = 3.1 Hz, CH), 130.1 (CH),
3
3
General procedure for the one-pot, three-component synthesis of
2
a-aminophosphonates: TSIL (0.018 g, 0.1 mmol) was added to a
131.2 (C), 140.0 (C), 146.6 (d, JP–C = 14.5 Hz, C). Compound 4g:
white solid, mp 87 °C; 1H NMR (500 MHz, CDCl3): d 3.51 (d,
J = 10.5 Hz, 3H), 3.81 (d, J = 10.6 Hz, 3H), 4.82 (d, J = 24 Hz, 1H),
4.84 (br s, 1H), 6.64 (d, J = 8.0 Hz, 2H), 6.74 (t, J = 7.2 Hz, 1H),
7.10 (t, J = 7.7 Hz, 2H), 7.30 (t, J = 7.5 Hz, 1H), 7.39 (t, J = 7.4 Hz,
mixture of aldehyde/ketone (2 mmol) and amine or amine deriva-
tive (2.2 mmol) in water (1 mL) at room temperature. The mixture
was stirred at room temperature for 10 min and then trimethyl
2H), 7.50 (d, J = 7.3 Hz, 2H); 13C NMR (125 MHz, CDCl3): d 54.1 (d,
Table 1
1
2JP–C = 7.0 Hz, OCH3), 54.2 (2JP–C = 6.8 Hz, OCH3), 56.2 (d, JP–C
=
Synthesis of
a-aminophosphonates from aldehydes or a ketone, amines and
3
150 Hz, CH), 114.3 (CH), 119.0 (CH), 128.2 (d, JP–C = 5.8 Hz, CH),
128.4 (d, JP–C = 3.1 Hz, CH), 129.1 (CH), 131.2 (CH), 136.0 (C),
146.6 (d, JP–C = 14.5 Hz, C).
trimethylphosphite
3
R1
R2
R3
Time (h)
Yield (%)
2
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
4-ClC6H4
4-O2NC6H4
2-Furyl
4-Pyridyl
4-MeOC6H4
Benzyl
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
15 min
15 min
1
1
2
0.5
10 min
0.5
0.5
1
1
1
15 min
2
1
96
98
95
94
96
98
98
96
95
97
94
92
98
95
92
96
Acknowledgement
This research was supported by the National Research Council
of the Islamic Republic of Iran as National Research project number
984.
Phenyl
4-NCC6H4
4-MeC6H4
i-Propyl
Cinnamyl
4-MeOC6H4
Phenyl
Phenyl
Phenyl
Phenyl
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