SO3H-functionalized ionic liquids catalyzed the synthesis of α-aminophosphonates in aqueous media

Article abstract of DOI:10.1002/hc.20644

SO₃H-functionalized halogen-free ionic liquids were prepared and used as efficient and recyclable catalysts for the synthesis of α-aminophosphonates at room temperature via the one-pot three-component condensation reaction in aqueous media with good yields of 80-96%. The postprocessing was simple, and the catalysts could be reused at least six times without noticeably decreasing the catalytic activity.

Full text of DOI:10.1002/hc.20644

Heteroatom Chemistry
Volume 21, Number 7, 2010
SO H-Functionalized Ionic Liquids Catalyzed
3
the Synthesis of α-Aminophosphonates in
Aqueous Media
Dong Fang,1,2 Changmei Jiao,2 and Chunjie Ni2
1Jiangsu Provincial Key Laboratory of Coast Wetland Bioresources & Environment Protection,
Yancheng 224002, People’s Republic of China
2School of Chemistry & Chemical Engineering, Yancheng Normal University, Yancheng 224002,
People’s Republic of China
Received 27 July 2010; revised 11 September 2010
Some synthetic methods including one-pot synthe-
ABSTRACT: SO3H-functionalized halogen-free ionic
sis of α-aminophosphonates have been explored in
liquids were prepared and used as efficient
the presence of Lewis acids [2–6], Brønsted acids [7–
and recyclable catalysts for the synthesis of α-
8], solid acids [9–10], rare metal salts [11], or metal
aminophosphonates at room temperature via the
oxides [12] over recent decades.
one-pot three-component condensation reaction in
One of the prime concerns of industry and
aqueous media with good yields of 80–96%. The post-
academia is the search for replacements to the en-
processing was simple, and the catalysts could be
vironmentally damaging solvents/catalysts used on
reused at least six times without noticeably decreas-
a large scale, especially those that are volatile and
ꢀ
C
ing the catalytic activity. 2010 Wiley Periodicals, Inc.
difficult to handle. Ionic liquids have been turned to
be a kind of promising alternative medium/catalysts
for various chemical processes, of which function-
Heteroatom Chem 21:546–550, 2010; View this article on-
line at wileyonlinelibrary.com. DOI 10.1002/hc.20644
alized ionic liquids (FILs) have been one of the
most exciting topics. In view of both the advan-
INTRODUCTION
tages and disadvantages of homogeneous and het-
erogeneous catalytic system, the use of FILs as re-
action media/catalytic system may be in terms of
settlement to both the solvent emission and cat-
alytic recycling problem in traditional chemical pro-
cedure. However, very few papers were concerned
with the synthesis of α-aminophosphonates in the
presence of ionic liquids. Yadav et al. used ionic liq-
uids [bmim]BF4/[bmim]PF6 as novel reaction media
for the synthesis of α-aminophosphonates [13]. Very
recently, Akbari and Heydari used imidazolium-
based ionic liquid [bsmim][CF3SO3] and Sadaphal
et al. used [bnmim][HSO4] as the recyclable catalyst
for the synthesis of α-aminophosphonates, respec-
tively [14,15]. However, typical ionic liquids consist
of halogen-containing anions (e.g., [PF6]−, [BF4]−,
α-Aminophosphonates have received considerable
attention in medicinal chemistry for their broad bi-
ological activities such as peptide mimics, enzyme
inhibitors, antibiotics, and catalytic antibodies[1].
Correspondence to: Fang Dong; e-mail: fang-njust@hotmail
.com.
Contract grant sponsor: Educational Commission of Jiangsu
Provinces.
Contract grant number: 07KJD530238.
Contract grant sponsor: Jiangsu Provincial Key Laboratory of
Coastal Wetland Bioresources & Environmental Protection.
Contract grant number: JLCBE 09023.
Contract grant sponsor: Professional Elite Foundation of
Yancheng Normal University.
c
ꢀ
2010 Wiley Periodicals, Inc.
546

SO3H-Functionalized Ionic Liquids Catalyzed the Synthesis of α-Aminophosphonates in Aqueous Media 547
TABLE 1 Effect of the Different Catalysts on the Synthesis
of α-Aminophosphonatesa
N
N
SO3H
A
n
Entry
Catalyst (mmol)
Time (min) Isolated Yield (%)
1
2
3
4
5
6
7
8
0
120
60
30
30
30
60
60
60
60
30
30
60
60
60
0
78
92
92
91
65
80
81
53
79
79
50
82
82
FILs [psmim][HSO4] : n=1, A=HSO4;
[psmim][HSO4] (0.5)
[psmim][HSO4] (1.0)
[psmim][HSO4] (1.5)
[psmim][HSO4] (2.0)
[psmim][H2PO4] (0.5)
[psmim][H2PO4] (1.0)
[psmim][H2PO4] (1.5)
[bsmim][HSO4] (0.5)
[bsmim][HSO4] (1.0)
[bsmim][HSO4] (1.5)
[psmim][H2PO4] (0.5)
[psmim][H2PO4] (1.0)
[psmim][H2PO4] (1.5)
[psmim][ H2PO4] : n=1, A= H2PO4;
[bsmim][HSO4] : n=2, A=HSO4;
[bsmim][ H2PO4] : n=2, A= H2PO4;
SCHEME 1 Structure of FILs.
9
10
11
12
13
14
[CF3COO]−, [CF3SO3]−, or [(CF3SO2)2N]−), which in
some regard limits their “greenness” [16,17]. Thus,
it is necessary to synthesize less expensive and
halogen-free ionic liquids that can be used in sim-
ple procedures. In fact, the search for new, readily
available, and green catalysts is still being actively
pursued.
a10 mmol benzaldehyde, 10 mmol aniline, 10 mmol triethyl phosphite,
and 0.5 mL H2O; r.t.
RESULTS AND DISCUSSION
We are especially interested in preparation
and developing the potential use of efficient,
simple and readily available FIL catalysts, and
some novel SO3H-functional halogen-free acidic
ionic liquids have been prepared and their cat-
alytic activities for acid-catalyzed reactions have
also been investigated previously [18,19]. In con-
tinuation of our work, we report here the
preparation of SO3H-functionalized halogen-free
ionic liquids ([psmim][HSO4], [psmim][H2PO4],
[bsmim][HSO4]), and [bsmim][H2PO4] (Scheme 1),
and their uses as the novel catalysts in one-pot,
three-component condensation in water have also
been investigated (Scheme 2). To the best of our
knowledge, such FILs used for the synthesis of α-
aminophosphonates have not been reported in the
open literature.
To begin with catalytic activity experiments, ben-
zaldehyde, aniline, and triethyl phosphite were em-
ployed as the model reactants at room temperature
in FILs for a length of time to compare the catalytic
performance (Table 1). It was shown that no desir-
able product could be detected when a mixture of
benzaldehyde, aniline, and triethyl phosphite was
stirred at room temperature for 120 min in the ab-
sence of FILs (entry 1), which indicated that the
catalysts were absolutely necessary for this one-pot
three-component reaction.
All the FILs were proved to be very active,
and it is clear that the yield was increased with the
increase in FILs and the optimal amount of FILs was
1.0 mmol (entry 3, 7, 10, and 13), leading to 79–92%
yield of α-aminophosphonates in the presence of
10% mmol FILs. Higher amount of the catalysts
could not improve the yield obviously. It is suggested
that the increase in acidity of FILs should facili-
tate the reaction and may decrease the amount of
catalyst [15]. In addition, ionic liquids containing the
FILs [psmim][HSO4]: n = 1, A = HSO4
[psmim][H2PO4]: n = 1, A = H2PO4
[bsmim][HSO4]: n = 2, A = HSO4
[bsmim][H2PO4]: n = 2, A = H2PO4
O
R2
P(OEt)3
NH
O
R1
H
FILs(10 mol%)
H2O , rt
or
P
1
R1
OEt
OEt
+
H
H(O)P(OEt)2
R2NH2
4
3
2
SCHEME 2 Synthesis of α-aminophosphonates via one-pot three-component condensation reaction catalyzed by FILs.
Heteroatom Chemistry DOI 10.1002/hc

548 Fang, Jiao, and Ni
TABLE 2 Influence of the Amounts of Water on the Synthe-
sis of α-Aminophosphonatesa
ferent from the literature [14]. As a clean and cheap
solvent, it is important to carry out the reaction in
water for the environmental and economic reasons,
as well as the workup procedure. Then, effect of the
amount of water on the reaction was explored and
the results are listed in Table 2.
The recycling performance of the [psmim]
[HSO4] was also investigated using the above-
mentioned model reaction. After completion of the
reaction, the products were isolated from the cat-
alytic system by filtration; the catalyst contained in
filtrate was reused in the next run after the extrac-
tion with CH2Cl2. The catalyst can be reused at least
six times without an appreciable decrease in yield
and the reaction rate, more than 90% yield of α-
aminophosphonates could be obtained in each re-
cycle. Compared with the traditional solvents and
catalysts, the easy recycling performance is also an
attractive property of the FILs for the environmental
protection and economic reasons.
Then, this condensation reaction with various
aldehydes, amines, and tri/diethyl phosphite in the
presence of [psmim][HSO4] as the catalyst was
explored under the optimized reaction conditions
described above, and the results are presented in
Table 3.
It can easily be seen that this one-pot,
three-component condensation completed within
20–60 min, and the products were isolated in
good yields by filtration. For aromatic aldehy-
des carrying either electron-donation or electron-
withdrawing substituents could afford good yields
Entry
Water (mL)
Isolated Yield (%)
1
2
3
4
5
6
7
8
0
92
92
91
90
87
85
83
81
0.5
1.0
2.0
4.0
6.0
8.0
10.0
a10 mmol benzaldehyde, 10 mmol aniline, 10 mmol triethyl phosphite,
and 1 mmol [psmim][HSO4]; r.t., 30 min.
shorter length of alkyl chain are relatively inexpen-
sive. Furthermore, the better immiscibility of the
resulted α-aminophosphonates with the FILs con-
taining shorter length of alkyl chain should facili-
tate the separation in the workup procedure. Hence,
[psmim][HSO4] should be the best catalyst for this
procedure among the four FILs and the optimized re-
action conditions are presented in Table 1 (entry 3).
The chemical industry is under considerable
pressure to replace many of the volatile organic com-
pounds that are currently used as solvents in organic
synthesis. For overcoming these problems, one ap-
proach is to use the water as the green medium,
another approach is to develop new processes in-
volving the solvent-free conditions. To our surprise,
the reaction could be carried out either in aqueous
media or under solvent-free condition, which is dif-
TABLE 3 One-Pot Three-Component Condensation for α-Aminophosphonatesa
Entry
R1
R2
3
Time (min)
Yieldb%
1
2
3
4
5
6
7
8
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3C6H4
C H5
C H5
6
P(OEt)3
H(O)P(OEt)2
P(OEt)3
H(O)P(OEt)2
H(O)P(OEt)2
H(O)P(OEt)2
H(O)P(OEt)2
H(O)P(OEt)2
P(OEt)3
H(O)P(OEt)2
P(OEt)3
P(OEt)3
P(OEt)3
P(OEt)3
60
60
60
60
60
60
60
60
30
30
60
60
20
20
30
30
60
60
90
91
93
95
82
81
83
80
92
90
89
89
96
96
93
93
86
80
C6H5
4-CH3C6H4
4-NO2C6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
C H5
9
C6H5
10
11
12
13
14
15
16
17
18
C6H5
C6H5
C6H5
3-NO2C6H4
4-NO2C6H4
C H5
6
C6H5
6
2-ClC6H4
4-ClC6H4
4-HOC6H4
4-NO2C6H4
butyl
C6H5
C6H5
P(OEt)3
P(OEt)3
P(OEt)3
P(OEt)3
C6H5
C6H5
Cyclohexyl
C6H5
6
a10 mmol benzaldehyde, 10 mmol aniline, 10 mmol tri/diethyl phosphite, 1 mmol [psmim][HSO4], and 0.5 mL H2O; r.t.
bIsolated yields.
Heteroatom Chemistry DOI 10.1002/hc

SO3H-Functionalized Ionic Liquids Catalyzed the Synthesis of α-Aminophosphonates in Aqueous Media 549
of α-aminophosphonates (entries 2, 13–16). In the
General Procedure for Synthesis of
case of anilines, it is noteworthy that both the
electron-donating and electron-withdrawing sub-
stituents (entries 3–7) were advantageous to this re-
action. In addition, both triethyl phosphite and di-
ethyl phosphite could be employed to carry out the
condensation.
α-Aminophosphonates Catalyzed by FILs
In a typical experiment, to a round-bottomed flask
charged with aldehyde (10 mmol) and aniline
(10 mmol) in water of 0.5 mL, FIL (1.0 mmol) was
added under stirring. The mixture was stirred at
room temperature for 5 min, and then tri/diethyl
phosphite (10 mmol) was added. On completion
(monitored by TLC), the products were separated
by filtration and dried under vacuum. The products
CONCLUSION
1
were identified by H NMR and physical data (mp)
In summary, some readily available SO3H-
functionalized halogen-free ionic liquids were
prepared and behaved as the novel recyclable
catalysts for one-pot synthesis of a variety of α-
aminophosphonates at room temperature in aque-
ous media; the procedure offers several advan-
tages including short reaction time, good yields,
and easy workup procedures; and this method is
useful addition to the present methodology for α-
aminophosphonates.
matches with the literature.
Selected Spectral Data for α-Aminophosphonates
Diethy(phenyl)-N-(phenyl)aminomethylphosphonate
(entry 9): White solid, mp 89–90◦C(lit. 90–91◦C) [12],
1H NMR, δ: 1.02 (t, J = 7.0 Hz, 3H), 1.17 (t, J = 7.0
Hz, 3H), 3.36 (s, 1H), 3.72–3.64 (m, 1H), 3.90–3.82
(m, 1H), 4.09–3.99 (m, 2H), 5.02 (d, J = 24.9 Hz,
1H), 6.52 (t, J = 7.1 Hz, 1H), 6.78 (d, J = 8.0 Hz,
2H), 6.99 (t, J = 7.75 Hz, 2H), 7.32–7.20 (m, 3H),
7.52 (d, J = 7.2 Hz, 2H).
Diethy(phenyl)-N-(phenyl)aminomethylphospho-
nate (entry 11): Yellow solid, mp 124–125◦C (lit.124–
EXPERIMENTAL
1
126◦C) [12], H NMR, δ: 1.04 (t, J = 7.0 Hz, 3H),
Melting points were determined by use of an X6-
Data microscope apparatus. The IR spectra were run
on a Bruker Vectter 22 spectrometer and expressed
1.17 (t, J = 7.0 Hz, 3H), 3.37 (brs, 1H), 3.76–3.68
(m,1H), 3.93–3.85 (m, 1H), 4.09–4.02 (m, 2H), 5.23
(d, J = 24.3 Hz, 1H), 7.27–7.20 (m, 3H), 7.33 (t,
J = 7.5 Hz, 3H), 7.54 (d, J = 7.1 Hz, 2H), 7.68 (d,
J = 2.0 Hz, 1H).
1
in cm−1 (KBr). H NMR spectra were recorded on
a Bruker DRX300 (300 MHz) spectrometer. 13C
NMR spectra were recorded on a Bruker DRX300
(75 MHz) spectrometer. Mass spectra were obtained
with an automated Fininigan TSQ Quantum Ultra
AM (Thermal) LC-MS spectrometer. All chemicals
(AR grade) were commercially available and used
without further purification.
Diethy(2-cholorophenyl)-N-(phenyl)aminomethy-
lphosphonate (entry 13): White solid, mp 59–60◦C
1
(lit. 60◦C) [12], H NMR (300 MHz, DMSO-d6), δ:
0.99 (t, J = 7.0 Hz, 3H), 1.22 (t, J = 7.0 Hz, 3H), 3.37
(d, J = 6.2 Hz, 1H), 3.67–3.64 (m, 1H), 3.86–3.83
(m, 1H), 4.13–4.07 (m, 2H), 5.20 (d, J = 25.0 Hz,
1H), 6.55(t, J = 7.0 Hz, 1H), 6.68 (d, J = 7.9 Hz.
2H), 7.03 (t, J = 7.1 Hz, 2H), 7.32–7.27 (m, 2H),
7.45 (d, J = 7.5 Hz, 1H), 7.69–7.66 (m, 1H).
Preparation of SO3 H-Functionalized
Halogen-Free Ionic Liquid
All used acyclic SO3H-functionalized halogen-free
acidic ionic liquids were synthesized according to
our previous methods [20]. The FILs were analyzed
by 1H NMR, 13C NMR, and MS spectroscopic meth-
ods, and the spectral data agreed with their struc-
tures (Scheme 1).
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