Phosphomolybdic acid: An efficient and reusable catalyst for the synthesis of β- Phosphono malonates

Article abstract of DOI:10.1007/BF03246216

Phosphomolybdic acid (H₃PMo₁₂O₄₀) is an efficient and reusable catalyst for the synthesis of the phospha-Michael addition of phosphite esters with different types of α,β- Unsaturated malonates to produce a variety of β- Ph

Full text of DOI:10.1007/BF03246216

J. Iran. Chem. Soc., Vol. 8, No. 1, March 2011, pp. 198-203.
JOUIRrNaAnLiaOnF THE
Chemical Society
ꢀꢀꢀꢀꢀꢀꢀꢀ
Phosphomolybdic Acid: An Efficient and Reusable Catalyst for the Synthesis of β-
Phosphono Malonates
S. Sobhani* and S. Rezazadeh
Department of Chemistry, College of Sciences, Birjand University, Birjand 414, Iran
(Received 10 May 2010, Accepted 24 June 2010)
Phosphomolybdic acid (H3PMo12O40) is an efficient and reusable catalyst for the synthesis of the phospha-Michael addition of
phosphite esters with different types of α,β-unsaturated malonates to produce a variety of β-phosphono malonates.
Keywords: β-Phosphono malonates, Heteropoly acid, Phospha-Michael addition, Phosphite esters, Malonates
INTRODUCTION
high temperature; long reaction times; low yields; tedious
work-up protocols; requiring a promoter such as microwave
and using large amounts of un-recyclable catalyst which
would eventually result in the generation of a large amount of
toxic waste. Hence, the development of a new and efficient
catalyst for this important transformation is still in demand.
For the last two decades, the use of heteropoly acids as
environmentally benign catalysts has become important in
industries related with fine chemicals [17]. Heteropoly acids,
especially those comprising the strongest Keggin-type
structure such as H3PW12O40, H3PMo12O40 and H4SiW12O40,
are more active catalysts than the conventional inorganic and
organic acids [17-20]. In addition, solid heteropoly acids are
soluble in water and polar organic solvents such as lower
alcohols and carboxylic acids, but insoluble in hydrocarbons
[21]. These properties make it possible to recover heteropoly
acids from the reaction mixture without neutralization, simply
by extracting with H2O or precipitating by a hydrocarbon
solvent [21].
Synthesis of phosphonate derivatives has considerably
attracted the attention of organic chemists due to their wide
range of applications in agriculture and bio-chemistry. For
example, phosphonate derivatives are used as insecticides,
herbicides, fungicides and plant-growth regulators in the area
of agricultural chemistry [1]. They play an important role in
our lives as antiviral agents and in mammalian cells as
inhibitors of gene expression. They also play an important role
in the treatment of bone disorders and in medical
decalcification [2-4].
Direct phosphorus-carbon bond formation represents one of
the most versatile and powerful tools for the synthesis of
phosphonates. Amongst these methods, phospha-Michael
addition, that is, the addition of a phosphorous nucleophile to
an electron-deficient alkene has received remarkable attention
from organic chemists [5,6]. These reactions are most
commonly promoted by bases [5-9], acids [10,11],
microwaves [12], transition metals [13,14] or radical initiators
such as AIBN [15,16]. Although these methods are valuable,
they suffer from one or more of the following disadvantages:
ꢀ
Recently, we have focused our efforts on the development
of useful and novelmethods for the synthesis of phosphonate
derivatives [22-31]. In this connection, herein, we report the
successful synthesis of β-phosphono malonates via phospha-
Michael addition of trialkyl phosphites to α,β-unsaturated
*Corresponding author. E-mail: ssobhani@birjand.ac.ir

Sobhani & Rezazadeh
2
malonates catalyzed by heteropoly acids as recyclable
catalysts.
4.46 (dd, 1H, 3JHH = 8.2, JHP = 21.2 Hz), 4.61 (t, 1H, 3JHH
=
3
8.5 Hz), 7.35 (d, 2H, JHH = 4 Hz), 7.47 (s, 1H), 7.75 (d, 1H,
3JHH = 5.3 Hz) ppm; 13C NMR (CDCl3, TMS): δ 16.0 (d, 3JCP
=
3
1
EXPRIMENTAL
6.3 Hz), 16.2 (d, JCP = 5.6 Hz), 24.9, 39.4 (d, JCP = 144.6
2
2
Hz), 63.6 (d, JCP = 7.5 Hz), 64.4 (d, JCP = 6.9 Hz), 110.9 (d,
3JCP = 5.6 Hz), 111.1, 127.8, 128.6, 129.6, 130.6, 135.1 ppm;
31P NMR (CDCl3, TMS): δ 19.47 ppm; MS (70 eV), m/e: 326
(M+), 328 (M++2), 189 [M+-P(O)(OEt)2], 191 [(M++2)-
P(O)(OEt)2].
Chemicals and Apparatus
Chemicals were purchased from Merck and Fluka
Chemical Companies. All of the products were identified
by their physical and spectral data. NMR spectra were
recorded in ppm in CDCl3 on a Bruker Avance DPX-250
instrument using TMS as internal standard. Mass spectra
were recorded on a Shimadzu GCMS-QP5050A. The purity
of the products and the progress of the reactions were
accomplished by TLC on silica-gel polygram SILG/UV254
plates.
[1-(4-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid
1
diethyl ester (2c). H NMR (CDCl3, TMS): δ 1.16 (t, 3H,
3
3JHH = 7.0 Hz), 1.33 (t, 3H, JHH = 7.0 Hz), 3.62 (dd, 1H,
3JHH = 7.5 Hz, 2JHP = 21.5 Hz), 3.82-4.19 (m, 4 H), 4.55 (t, 1H,
3JHH = 7.7 Hz), 7.42 (s, 4H) ppm; 13C NMR (CDCl3, TMS): δ
3
3
16.1 (d, JCP = 5.0 Hz), 16.2 (d, JCP = 5.6 Hz), 25.5, 43.9 (d,
1JCP = 144.7 Hz), 63.5 (d, JCP = 7.0 Hz), 64.4 (d, JCP = 7.0
2
2
3
3
General Procedure for the Synthesis of β-
Phosphono Malonates (2a-o)
Hz), 111.0 (d, JCP = 11.9 Hz), 111.2 (d, JCP = 11.3 Hz),
128.8, 129.6, 130.7, 135.7 ppm; 31P NMR (CDCl3, TMS): δ
19.42 ppm; MS (70 eV), m/e: 326 (M+), 328 (M++2), 189 [M+-
P(O)(OEt)2], 191 [(M++2)-P(O)(OEt)2].
H3PMo12O40 (0.02 mmol) was added to a stirring mixture
of α,β-unsaturated malonates (1a-o) (1 mmol) and P(OEt)3 (1
mmol) at ambient temperature or at 80 °C (Table 2). The
reaction mixture was stirred for the appropriate time (Table 2).
n-Hexane was added to the reaction mixture. The catalyst was
separated from the resulting mixture by filtration and washed
with n-hexane (2 × 10 ml). Evaporation of the solvent of the
filtrate under reduced pressure gave the crude products. The
pure products were isolated by chromatography on silica gel
eluted with n-hexane:EtOAc (1:1).
[1-(Naphthalen-2-yl)-2,2-dicyanoethyl] phosphonic acid
1
diethyl ester (2h). H NMR (CDCl3, TMS): δ 1.08 (t, 3H,
3JHH = 7.0 Hz), 1.36 (t, 3H, 3JHH = 7.0 Hz), 3.65-4.22 (m, 5H),
4.66 (t, 1H, 3JHH = 8.5 Hz), 7.52-7.58 (m, 3H), 7.87-7.96 (m,
4H) ppm; 13C NMR (CDCl3, TMS): δ 16.1 (d, JCP = 5.6 Hz),
3
3
1
16.2 (d, JCP = 6.2 Hz), 25.7, 44.8 (d, JCP = 144.0 Hz), 63.4
(d, 2JCP = 7.5 Hz), 64.4 (d, 2JCP = 7.0 Hz), 111.2 (d, 3JCP = 13.2
3
Hz), 111.3 (d, JCP = 8.2 Hz), 125.9, 126,9, 127.2, 127.6,
127.7, 127.8, 128.2,129.2, 129.4, 133.3 ppm; 31P NMR
(CDCl3, TMS): δ 19.95 ppm.
Spectral Data for Selected Product
[1-Phenyl-2,2-dicyanoethyl] phosphonic acid diethyl
[1-(Furan-2-yl)-2,2-dicyanoethyl] phosphonic acid
1
1
esterꢀ(2a). H NMR (CDCl3, TMS): δ 1.11 (t, 3H, 3JHH = 6.8
diethyl ester (2i). H NMR (CDCl3, TMS): δ 1.24-1.37 (m,
3
3
2
Hz), 1.33 (t, 3H, JHH = 7.0 Hz), 3.65 (dd, 1H, JHH = 8.0,
6H), 3.87 (dd, 1H, 2JHH = 6.5 Hz, JHP = 22.7 Hz), 3.98- 4.23
2JHP = 21.0 Hz), 3.91-4.21 (m, 4H), 4.55 (t, 1H, JHH = 8.3
(m, 4H), 4.51 (t, 1H, 2JHH = 8.7 Hz), 6.44 (s, 1H), 6.62 (s, 1H),
7.49 (s, 1H) ppm; 13C NMR (CDCl3, TMS): δ 16.1, 16.2, 24.3,
3
Hz), 7.43 (s, 5H) ppm; 13C NMR (CDCl3, TMS): δ 16.1 (d,
3JCP = 5.6 Hz), 16.2 (d, JCP = 5.6 Hz), 25.5, 44.6 (d, JCP
=
39.1 (d, JCP = 147.1 Hz), 63.9 (d, JCP = 6.9 Hz), 64.2 (d,
3
1
1
2
2
2
3
3
144.0 Hz), 63.4 (d, JCP = 7.5 Hz), 64.4 (d, JCP = 7.0 Hz),
2JCP = 6.9 Hz), 110.9 (d, JCP = 9.4 Hz), 111.1 (d, JCP = 11.9
Hz), 111.3, 111.7, 143.2, 144.0 ppm; 31P NMR (CDCl3, TMS):
δ 19.88 ppm; MS (70 eV), m/e: 282 (M+), 145 [M+-
P(O)(OEt)2].
3
3
111.1 (d, JCP = 12.5 Hz), 111.3 (d, JCP = 10.0 Hz), 129.2,
129.3, 129.4, 129.8 ppm; 31P NMR (CDCl3, TMS): δ 20.04
ppm; MS (70 eV), m/e: 292 (M+), 155 [M+-P(O)(OEt)2].
[1-(2-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid
[1-(Pyridin-3-yl)-2,2-dicyanoethyl] phosphonic acid
diethyl ester (2b). 1H NMR (CDCl3, TMS): δ 1.11 (t, 3H, JHH
diethyl ester (2k). H NMR (CDCl3, TMS): δ 1.18 (t, 3H,
3
1
= 7.0 Hz), 1.36 (t, 3H, 3JHH = 7.0 Hz), 3.75-4.30 (m, 4H),
3JHH = 6.8 Hz), 1.33 (t, 3H, 3JHH = 7.0 Hz), 3.65 (dd, 1H, 3JHH
=
ꢀ
199

Phosphomolybdic Acid: An Efficient and Reusable Catalystꢀ
6.8 Hz, 2JHP = 21.6 Hz), 3.92-4.21 (m, 4H), 4.63 (t, 1H, 3JHH
=
8.5 Hz), 7.39 (t, 1H, 3JHH = 6.5 Hz), 7.95 (d, 1H, 3JHH = 6.5
Hz), 8.67 (s, 2H) ppm; 13C NMR (CDCl3, TMS): δ 16.1 (d,
O
R'
P(OEt)2
R'
CN
CN
H3PMo12O40 (2 mol%)
solvent-free
P(OEt)3
R
+
R
3
1
3JCP = 5.0 Hz), 16.2 (d, JCP = 5.0 Hz), 25.3, 42.1 (d, JCP
=
CN
1a-o
CN
2
2
144.6 Hz), 63.8 (d, JCP = 7.0 Hz), 64.5 (d, JCP = 7.0 Hz),
2a-o
3
3
110.8 (d, JCP = 10.7 Hz), 111.0 (d, JCP = 11.9 HZ), 124.0,
126,7, 136.5, 150.5, 150.8 ppm; 31P NMR (CDCl3, TMS): δ
19.03 ppm; MS (70 eV), m/e: 293 (M+), 156 [M+-P(O)(OEt)2].
1,1-Dicyanopentan-2-yl phosphonic acid diethyl ester
(2l). H NMR (CDCl3, TMS): δ = 1.00 (t, 3H, JHH = 7.0 Hz),
1.37 (t, 6H, JHH = 7.0 Hz), 1.61 (q, 2H, JHH = 7.0 Hz), 1.73-
R=aryl, heteroaryl, alkyl
R'=H,alkyl
Scheme 1
1
3
3
3
unsaturated malonates with triethyl phosphite were examined
in the presence of H3PMo12O40 to show the generality and
scope of the method (Scheme 1). The results of these studies
are summarized in Table 2.
2.10 (m, 2H), 2.29-2.34 (m, 1H), 4.16-4.25 (m, 4H), 4.29-4.35
3
(m, 1H). 13C NMR (CDCl3, TMS): δ = 13.73, 16.3 (d, JCP
=
3
1
5.6 Hz), 20.7 (d, JCP = 7.6 Hz), 29.2, 37.8 (d, JCP = 144.9
3
3
Hz), 110.7 (d, JCP = 5.0 Hz), 112.2 (d, JCP = 17.0 Hz). MS
As it is obvious from Table 2, the catalytic phospha-
Michael addition of triethyl phosphite with benzylidenemalo-
nitriles containing different electron-donating and electron-
withdrawing groups proceeded well and the desired products
(2a-g) were obtained in good to high yields (entries 1-7). In
the reaction of 1b-d and 1g, the catalyst was compatible with
functional groups such as Cl, Br and O-Me. No competitive
nucleophilic methyl ether cleavage was observed for the
substrate possessing an aryl-O-Me group (entry 7), despite the
strong nucleophilicity of phosphites. α,β-Unsaturated
malonates substituted with polyaromatic and heteroaromatic
groups underwent successful phospha-Michael addition by
triethyl phosphite (entries 8-11). This method is also
applicable for the synthesis of β-phosphono malonates from
the reaction of triethyl phosphite with α,β-unsaturated
malonates substituted with aliphatic groups (1l and 1m).
Similar reactions with β,β-disubstituted malonates (1n and 1o)ꢀ
led to the formation of the desired product in good yields
(70 eV): 259 (M++1), 121 [M+-P(O)(OEt)2].
RESULTS AND DISSCUSIONS
At first, the ability of some heteropoly acids such as
H3PMo12O40, H3PW12O40, H4SiW12O40 and (NH4)3PMo12O40 in
the phospha-Michael addition of triethyl phosphite with
benzylidenemalonitrile (1a) under solvent-free conditions at
room temperature was investigated (Table 1). Amongst
heteropoly acids tested, H3PMo12O40 turned out to be the most
effective catalyst in terms of yield and reaction time (Table 1,
entry 1). In order to show the role of the catalyst, a similar
reaction in the absence of the catalyst was triggered. This
reaction led to the formation of the desired product (2a) in low
yield after 24 h (Table 1, entry 5), which was a good
indication of the crucial role of the catalyst in the reaction.
Then, the reaction of various structurally diverse α,β-
Table 1. Phospha-Michael Addition of Triethyl Phosphite to 1a Catalyzed by HPAs
Entry
Catalyst
H3PMo12O40
Time (h)
0.25
Yield (%)a
88
1
2
3
4
5
H3PW12O40
H4SiW12O40
(NH4)3PMo12O40
-
1
2
3
85
50
89
50
24
aIsolated yield; Conditions: 1a/phosphite/catalyst:1/1/0.02, room temperature, solvent-free.
ꢀ
200

Sobhani & Rezazadeh
Table 2. Synthesis of β-Phosphono Malonates Catalyzed by H3PMo12O40
Entry
1
Substrate
Product
Time (min)
15
Yield (%)a
88
CN
CN
2a
1a
Cl
CN
CN
2
3
5
82
95
2b
2c
1b
CN
CN
30
Cl
1c
CN
4
5
6
7
15
5
85
83
85
84
2d
2e
2f
CN
CN
CN
Br
1d
CN
CN
CN
O2N
1e
60
30
Me
1f
2g
CN
CN
MeO
1g
8
5
5
80
85
86
2h
2i
CN
CN
1h
9
O
CN
1i
1j
CN
10
30
2j
S
CN
N
CN
11
12
13
5
98
72
64
2k
2l
CN
1k
CN
4 hb
4 hb
CN
CN
1l
2m
CN
1m
CN
14
2 hb
4 hb
70
2n
2o
CN
CN
1n
ꢀ
15
71
CN
1o
ꢀ
aIsolated yield; Conditions: α,β-unsaturated malonate/phosphite/catalyst: 1/1/0.02. All the products were characterized
by spectroscopic methods and compared with the authentic spectra [32,33]. bReaction temperature = 80 °C.
ꢀ
201

Phosphomolybdic Acid: An Efficient and Reusable Catalystꢀ
(entries 14 and 15).
The possibility of recycling the catalyst was examined
using the reaction of benzylidenemalonitrile (1a) and triethyl
phosphite under solvent-free conditions at room temperature.
Upon completion of the reaction, n-hexane was added to the
reaction mixture. Then the catalyst was separated by a simple
filtration from the resulting heterogeneous mixture, washed
with n-hexane (3 × 30 ml), dried and reused for subsequent
runs. The recycled catalyst was reused five times without any
additional treatment. The average isolated yield of 2a for five
consecutive runs was 85%, which clearly demonstrates the
practical reusability of this catalyst (Fig. 1).
Finally, we have evaluated the generality of the present
method for the phospha-Michael addition of different
phosphite esters with benzylidenemalonitrile (1a). The results
of these studies are summarized in Table 3.
As it is shown in Table 3, 1a underwent catalytic phospha-
Michael addition with trimethyl/tri-iso-propyl phosphite and
the desired products were obtained in good yields (entries 1
and 2). A similar reaction in the presence of triphenyl
phosphite as a phosphorus nucleophile led to the formation of
the desired product in low yield (entry 3). No yield was
obtained when the reaction took place out in the presence of
diethyl phosphite.
Fig. 1. Reusability of H3PMo12O40 as a catalyst for the
synthesis of β-phosphono malonate 2a: (ꢀ) time,
(ꢁ) yield.
simple work-up, ease of catalyst recovery, no by-product
formation and using a catalytic amount of H3PMo12O40 make
this method attractive and a useful addition to the presently
existing methodologies.
ACKNOWLEDGMENTS
We are thankful to Birjand University Research Council
for their support of this work.
CONCLUSIONS
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H3PMo12O40 was found to be an efficient and reusable
catalyst for the synthesis of a variety of β-phosphono
malonates by phospha-Michael addition of phosphite esters
with different α,β-unsaturated malonates. Short reaction times,
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Time (h)
Yield (%)a
1b
2b
3
P(OMe)3
P(O-i-Pr)3
P(OPh)3
2
1
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73
78
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24
aIsolated yield; Conditions: 1a/phosphite/catalyst:1/1/0.02, room temperature, (except for entries 1
and 2), solvent-free. bReaction temperature = 50 °C.
ꢀ
202

Sobhani & Rezazadeh
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