Silica gel and polystyrene supported aluminum chloride as heterogeneous catalysts for the preparation of α-aminophosphonates

Article abstract of DOI:10.1002/hc.20629

Silica gel supported aluminum chloride (SiO₂-AlCl₃) and cross-linked polystyrene-supported aluminum chloride (PS-AlCl₃) are environment- friendly heterogeneous catalysts for the condensation of amines and aldehydes with diethyl phosphite to afford α-aminophosphonates. These solid acid catalysts are stable (as bench top catalysts) and can be easily recovered and reused without appreciable change in their efficiency.

Full text of DOI:10.1002/hc.20629

Heteroatom Chemistry
Volume 21, Number 6, 2010
Silica Gel and Polystyrene Supported
Aluminum Chloride as Heterogeneous
Catalysts for the Preparation of
α-Aminophosphonates
Kaveh Parvanak Boroujeni1 and Amir Nasrolahi Shirazi2
1Department of Chemistry, Shahrekord University, Shahrekord 115, Iran
2Department of Chemistry, Shiraz University, Shiraz 71454, Iran
Received 6 May 2010; revised 11 June 2010
convenient method for the preparation of these com-
ABSTRACT: Silica gel supported aluminum chloride
(SiO2-AlCl3) and cross-linked polystyrene-supported
aluminum chloride (PS-AlCl3) are environment-
friendly heterogeneous catalysts for the condensation
of amines and aldehydes with diethyl phosphite to af-
ford α-aminophosphonates. These solid acid catalysts
are stable (as bench top catalysts) and can be eas-
ily recovered and reused without appreciable change
pounds. Several types of catalysts were introduced
previously for this purpose, such as ZrCl4 [11], AlCl3
[12], LiClO4 [13], SiO2-NH4HCO3 [14], Al(OTf)3 [15],
ionic liquid [bmim]Cl-AlCl3 [16], Mg(ClO4)2 [17],
TiCl4 [18], Al2O3-SbCl3 [19], ZrOCl2·8H2O [20], TiO2
[21], amberlyst-15 [22], [Cu(3,4-tmtppa)](MeSO4)4
[23], sulfamic acid [24], FeCl3 [25], sodium dodecyl
sulfate [26], mesoporous aluminosilicate nanocage
[27], and H3BO3 [28]. Most of the above-mentioned
methods suffer from the drawbacks such as gener-
ation of environmentally perilous waste material,
tedious workup, long reaction times, the use of
malodorous trialkyl phosphite as the phospho-
rus nucleophile, unsatisfactory yields, complicated
operations, and the use of moisture-sensitive, expen-
sive, hazardous, difficult to handle, or unreusable
catalysts. Sometimes, some of the mentioned
catalysts do not work well with electron-deficient
amines and/or secondary amines. On the other
hand, the formation of α-hydroxyphosphonate or
a product of its rearrangement frequently accom-
panies the formation of α-aminophosphonates. In
view of these, the search for finding a cost-effective,
mild, and simple chemoselective protocol specially
using heterogeneous catalysts for the synthesis of
α-aminophosphonates is still relevant.
ꢀ
C
in their efficiency.
2010 Wiley Periodicals, Inc. Het-
eroatom Chem 21:418–422, 2010; View this article online
at wileyonlinelibrary.com. DOI 10.1002/hc.20629
INTRODUCTION
α-Aminophosphonates as a kind of natural amino
acid analogs occupy an important place and reveal
diverse and interesting biological and biochemical
properties [1–3]. Their potential as plant growth reg-
ulators [4], herbicidals [5], pharmacogenic agents
[6], antibiotics [7], enzyme inhibitors [8], HIV
protease [9], and antithrombotic agents [10] is well
documented. Three-component condensation of an
aldehyde, an amine, and a phosphite is the most
In recent years, the use of solid-supported cat-
alysts has received considerable attention in differ-
ent areas of organic synthesis due to their environ-
mental compatibility, moisture and air tolerance,
Correspondence to: Kaveh Parvanak Boroujeni; e-mail:
parvanak-ka@sci.sku.ac.ir.
Contract grant sponsor: Research Council of Shahrekord
University.
c
ꢀ
2010 Wiley Periodicals, Inc.
418

Silica Gel and Polystyrene Supported Aluminum Chloride as Heterogeneous Catalysts 419
SCHEME 1 One-pot preparation of α-aminophosphonates using SiO2–AlCl3 and PS–AlCl3.
nontoxicity, noncorrosiveness, easier handling, and
reusability, and the development of solventless pro-
tocol has an added advantage in the green con-
text [29]. In this pursuit, and during the course of
our ongoing interest in the application of hetero-
geneous Lewis acid catalysts in organic reactions
[30,31], we now wish to introduce SiO2-AlCl3 and
PS-AlCl3 for the synthesis of α-aminophosphonates
(Scheme 1).
tries 25, 27). However, under the same reaction con-
ditions the coupling reaction of ketones with aniline
and diethyl phosphite in the presence of PS-AlCl3
was very slow (entries 26,28). In another attempt, we
extend the efficiency of the method by using different
amines including different substituted anilines and
primary aliphatic amines in the condensation with
benzaldehyde and diethyl phosphite (entries 29–44).
As can be seen from Table 1 entries 33–40, the pres-
ence of electron-withdrawing substituents on the
aromatic ring in substituted anilines increases reac-
tion times and decreases the yields. We also decided
to test the feasibility of using secondary amines in
the synthesis of α-aminophosphonates, a transfor-
mation that is difficult to accomplish via conven-
tional methods. As it is evident from the results,
secondary amines such as piperidine, diethylamine,
and N-methylaniline afforded the corresponding α-
aminophosphonates in the presence of SiO2-AlCl3
in high yields (entries 45, 47, 49). The condensa-
tion of secondary amines with aldehydes and di-
ethyl phosphite in the presence of PS-AlCl3 failed
(entries 46, 48, 50). Noteworthy was that no com-
petitive side reactions such as the formation of α-
hydroxyphosphonates were observed in these trans-
formations. As the results show, SiO2-AlCl3 promotes
the reactions more effectively than PS-AlCl3. These
solid catalysts were stable under the reaction con-
ditions, and there is no leaching of acid moieties
during reactions.
It is worth noting that with excess AlCl3
in the absence of silica gel, condensation of 4-
methylbenzaldehyde, aniline, and diethyl phosphite
proceeded to the extent of only 74% in 5 h at
room temperature (vs. 91% conversion in 1.1 h,
Table 1, entry 3). Presumably, the less catalytic ac-
tivity of AlCl3 than SiO2-AlCl3 in synthesis of α-
aminophosphonates is due to its ability to strongly
complex Lewis base products. Unlike AlCl3, SiO2-
AlCl3 is a milder catalyst, which forms no stable com-
plex with starting materials and/or products. Fur-
thermore, the efficiency of SiO2-AlCl3 may also be
attributed to its large surface area and its remark-
able ability to act as a water scavenger.
RESULTS AND DISCUSSION
SiO2-AlCl3 was prepared by treating silica gel with
AlCl3 in refluxing carbon tetrachloride. PS-AlCl3
was prepared by addition of AlCl3 to cross-linked
polystyrene (8% divinylbenzene) in carbon disulfide
under reflux conditions. Using these catalysts, dif-
ferent aldehydes (aromatic and aliphatic) were con-
verted to their corresponding α-aminophosphonates
with diethyl phosphite and aniline in good to excel-
lent yields (Table 1). The best results in terms of
yield as well as reaction time were obtained using
SiO2-AlCl3 as catalyst under solvent-free conditions
at room temperature and using PS-AlCl3 in reflux-
ing acetonitrile, which proved to be the solvent of
choice among other organic solvents. The optimum
molar ratios of SiO2-AlCl3 and PS-AlCl3 to aldehyde
were found to be 0.1:1 and 0.15:1, respectively. Both
electron-deficient and electron-releasing benzalde-
hydes react efficiently with aniline to give the corre-
sponding α-aminophosphonates (entries 1–16). The
coupling reaction of naphthalene-2-carbaldehyde as
a polynuclear aromatic aldehyde with aniline and
diethyl phosphite also gave the corresponding prod-
uct in the presence of SiO2-AlCl3 and PS-AlCl3 in
high yields (entries 17,18). Aliphatic aldehydes need
slightly more time to produce corresponding α-
aminophosphonates (entries 19, 20). It was pleasing
to observe that even acid-sensitive substrates such
as cinnamaldehyde and furan-2-carbaldehyde gave
the corresponding α-aminophosphonates without
any decomposition, conjugate addition to the α,β-
unsaturated carbonyl group or generation of poly-
meric by-products under the present reaction condi-
tions (entries 21–24). Ketones also afforded the cor-
responding phosphates in relatively good yields (en-
The ability to recycle SiO2-AlCl3 and PS-AlCl3 is
a notable feature, since the catalysts were recov-
ered and reused five times for the preparation of
Heteroatom Chemistry DOI 10.1002/hc

420 Boroujeni and Shirazi
TABLE 1 SiO2-AlCl3 and PS-AlCl3 Catalyzed Synthesis of
α-Aminophosphonate Derivativesa
TABLE 1 (Continued)
Entry
Aldehyde
Amine
Time (h) Yield (%)b
Entry
Aldehyde
Amine
Time (h) Yield (%)b
37
38
2.51
42
85 [21]
79 [21]
1
2
11
22
93 [26]
93 [26]
39
2.61
81 [15]
3
4
1.11
2.12
91 [21]
90 [21]
40
42
75 [15]
1.21
2.22
95 [15]
91 [15]
5
6
1.31
2.22
92 [26]
94 [26]
41
42
1.41
2.32
90 [21]
89 [21]
7
8
1.51
32
90 [21]
90 [21]
43
44
1.81
4
89 [17]
–
9
0.91
1.52
94 [21]
94 [21]
45
46
10
47
1.91
90 [16]
1.31
2.92
90 [23]
85 [23]
48
49
(Et)2NH
4
1.8
–
11
12
90 [25]
50
PhMeNH
4
–
13
14
11
22
90 [26]
88 [26]
aRatio of catalyst:carbonyl compound:amine:diethyl phosphite is
0.1:1:1:1.2 for SiO2-AlCl13 and 0.15:1:1:1.2 for PS-AlCl23.
bIsolated yields. All products are known compounds and were iden-
tified by comparison of their physical and spectral data with those of
the authentic samples.
15
1.11
84 [21]
cThe reaction was carried out at 40◦C.
16
17
18
2.12
1.51
2.52
89 [21]
90 [15]
88 [15]
α-aminophosphonates without a significant de-
crease in their efficiency (Scheme 2).
19
20
21
3.52
90 [23]
88 [23]
A comparison of the efficiency of SiO2-AlCl3 cat-
alyst with some of those reported in the literature
is presented in Table 2. As it is seen in addition to
having the general advantages attributed to the solid
catalysts, SiO2-AlCl3 has a good efficiency compared
to many of those reported catalysts in the conden-
sation of aniline and 4-methoxybenzaldehyde with
diethyl phosphite.
In conclusion, in this paper we have used SiO2-
AlCl3 and PS-AlCl3 for the three-component cou-
pling reaction of aldehydes, amines, and diethyl
phosphite for the synthesis of α-aminophosphonates
21
22
1.91
3.52
70 [26]
67 [26]
23
24
1.41
3.42
90 [26]
70 [26]
25
26
2.11
4
80c [16]
10c [16]
27
28
2.11
3.52
88c [15]
30c [15]
29
30
0.91
1.82
94 [11]
92 [11]
31
32
11
2.12
90 [15]
90 [15]
33
34
21
3.52
81 [23]
78 [23]
35
2.11
83 [15]
36
3.72
79 [15]
SCHEME 2 Preparation of α-aminophosphonates using re-
covered SiO2–AlCl3 and PS–AlCl3.
(Continued )
Heteroatom Chemistry DOI 10.1002/hc

Silica Gel and Polystyrene Supported Aluminum Chloride as Heterogeneous Catalysts 421
TABLE 2 Comparison of the Efficiencies of a Number of Different Reported Catalysts with That of SiO2-AlCl3 in Condensation
of Aniline and 4-Methoxybenzaldehyde with Diethyl Phosphite
Entry
Catalyst/Solvent/Temperature
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
ZrCl4/MeCN/rt
5
3
2
90 [11]
90 [15]
95 [16]
95 [17]
92 [19]
95 [20]
98 [21]
90 [23]
87 [24]
92 [25]
98 [26]
90 [27]
92
Al(OTf)3/neat/80◦C
Ionic liquid [bmim]Cl–AlCl3/neat/rta
Mg(ClO4)2/neat/rt
5 min
3.5
5 min
2.5
3
Al2O3-SbCl3/MeCN/rt
ZrOCl2.8H2O/neat/rta
TiO2/neat/50◦C
[Cu(3,4-tmtppa)](MeSO4)4/H2O/80◦C
Sulfamic acid/neat/rt
9
2
10
11
12
13
FeCl3/THF/60◦C
0.75
30 min
4
Sodium dodecyl sulfate/H2O/50◦C
AlKIT-5b/MeCN/80◦C
SiO2-AlCl3/neat/rt
1.3
aWithbenzaldehyde.
bMesoporous aluminosilicate nanocage catalyst.
in good to excellent yields. The simplicity, easy
workup, low cost, easy preparation and handling of
the catalysts, and using diethyl phosphite instead of
nasty odor triethyl phosphite for the preparation of
α-aminophosphonates are the highlights of this pro-
cedure. In addition, the use of SiO2-AlCl3 and PS-
AlCl3 has resulted in a reduction in the unwanted
and hazardous waste that is produced during con-
ventional homogeneous processes.
rified by column chromatography (silica gel) using
n-hexane–EtOAc as eluent so as to afford the pure
product. The spent catalyst from different experi-
ments was washed with Et2O, dried and used again.
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Heteroatom Chemistry DOI 10.1002/hc

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