An eco-friendly procedure for one-pot synthesis of β- phosphonomalonates: Micellar solution of sodium stearate catalyzes tandem Knoevenagel-phospha-Michael reaction of aldehydes, malonitrile, and phosphites in aqueous media

Article abstract of DOI:10.1016/j.tet.2011.03.014

A new, one-pot convenient method for the synthesis of a variety of β-phosphonomalonates by a tandem Knoevenagel-phospha-Michael reaction of phosphite esters with aryl/heteroaryl/alkyl aldehydes and malonitrile in an aqueous micellar solution of sodium ste

Full text of DOI:10.1016/j.tet.2011.03.014

Tetrahedron 67 (2011) 3540e3545
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An eco-friendly procedure for one-pot synthesis of b-phosphonomalonates:
micellar solution of sodium stearate catalyzes tandem Knoevenagelephospha-
Michael reaction of aldehydes, malonitrile, and phosphites in aqueous media
*
Sara Sobhani , Zahra Pakdin Parizi
Department of Chemistry, College of Sciences, Birjand University, Birjand 414, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A new, one-pot convenient method for the synthesis of a variety of b-phosphonomalonates by a tandem
Received 18 August 2010
Received in revised form 3 March 2011
Accepted 7 March 2011
Knoevenagelephospha-Michael reaction of phosphite esters with aryl/heteroaryl/alkyl aldehydes and
malonitrile in an aqueous micellar solution of sodium stearate is described. This method offers several
advantages, such as using a cheap and environmentally benign reaction media, low loadings of sodium
stearate as catalyst and offers good yields.
Available online 12 March 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Micelle
b-Phosphonomalonates
Sodium stearate
Water
Aldehydes
Phosphites
1. Introduction
shortcomings still remains an ongoing challenge for the synthesis of
these significant scaffolds.
Phosphonates exhibit a wide range of notable biological proper-
ties, which expand their applications as enzyme inhibitors, metabolic
probes,1 peptide mimetics,2 antibiotics, and pharmacologic agents3
besides to their traditional roles as intermediates in organic synthe-
sis.4 Extensive efforts have been made to introduce convenient and
efficient methods for the synthesis of phosphonates. Direct phos-
phorusecarbon bond formation represents one of the most versatile
and powerful tools for the synthesis of phosphonates. Amongst the
methods for PeC bond formation, phospha-Michael addition, that is,
the addition of a phosphorous nucleophile to an electron-deficient
alkene has evoked remarkable attention by organic chemists.5 Syn-
Water is a desirable solvent for the reasons of cost, safety, and
environmental impact.6 In addition, reactions in aqueous media
illustrate unique reactivities and selectivities that are not usually
observed in organic media.7 However, organic solvents are still
used instead of water for mainly two reasons. First, most organic
substrates are not soluble in water and as a result, water cannot
function as a reaction medium. Second, many reactive substrates,
reagents, and catalysts are sensitive toward water and are decom-
posed or deactivated in aqueous media. A possible way to improve
the solubility of substrates is the use of surface active reagents that
can form micelles8 or vesicular structures in aqueous media. Mi-
celles are dynamic clusters of surfactant molecules, which posses
both hydrophilic and hydrophobic structures.9 It is well established
that in many cases, the rates and pathways of many chemical re-
actions can be altered by performing the reactions in micellar
media instead of pure bulk solvents. Micelles can concentrate the
reactants within a small volume, stabilize substrates, intermediates
or products, and orient substrates so that ionization potential,
oxidationereduction properties, dissociation constants, physical
properties, and reactivities are changed. Thus, they can alter the
reaction rate, mechanism, regio- and stereo-selectivity of the re-
action.10 The use of micellar and vesicle-forming surfactants as
catalysts is widespread and has been investigated in detail for
different reactions in aqueous solutions.11 However, from the
thesis of b-phosphonomalonates by this method are most commonly
promotedby bases,5aef Brønsted/Lewis acids,5gei transition metals,5j,k
radical initiators, such as AIBN5l,m or microwaves.5n Although these
methods are valuable, they suffer from one or more of the following
drawbacks, such as: low yields; high temperature; long reaction
times; requiring a promoter, such as microwave; using toxic solvents
or a large amount of catalyst and tedious work-up procedures.
Therefore, the development of a new method to overcome these
* Corresponding author. Tel.: þ98 561 2502008; fax: þ98 561 2502009; e-mail
addresses: sobhanisara@yahoo.com, ssobhani@birjand.ac.ir.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.014

S. Sobhani, Z.P. Parizi / Tetrahedron 67 (2011) 3540e3545
3541
viewpoints of practicability and applicability, the surfactant-aided
organic reactions are still at their preliminary stages.12
b-phosphonomalonates from various structurally diverse alde-
hydes. The results of this study are depicted in Table 2.
As part of our ongoing program directed toward the development
of new methods for the synthesis of phosphonate derivatives,13
recently we have introduced HClO4/SiO2 and H3PMo12O40 as effi-
As shown in Table 2, differently substituted benzaldehydes with
electron-donating and electron-withdrawing groups underwent
successful Knoevenagelephospha-Michael reaction with malono-
nitrile and triethyl phosphite (entries 1e7). The catalyst was com-
patible with functional groups, such as Cl, Br, and OeMe. No
competitive nucleophilic methyl ether cleavage was observed in
the substrate possessing an aryl-OeMe group (entry 1), despite the
strong nucleophilicity of phosphites. Acid-sensitive aldehydes, such
as furan-2-carbaldehyde and pyridine-3-carbaldehyde underwent
smooth reactions without any decomposition or polymerization
under the present reaction conditions (entries 8 and 9). This
cient catalysts for the two-pot synthesis of b-phosphonomalonates
by phospha-Michael addition of trialkyl phosphite to a,b-unsaturated
malonates.13j,k Herein, we wish to report the use of micellar solution
of sodium stearate in water as an efficient media for the one-pot
synthesis of b-phosphonomalonates directly from aldehydes, malo-
nonitrile, and trialkyl phosphites via tandem Knoevenagelephospha-
Michael reaction.
method is also applicable for the synthesis of b-phosphonomalo-
2. Results and discussion
nates from the reaction of triethyl phosphite with aliphatic alde-
hydes and malononitrile (entries 10 and 11). The reaction of
ketones with malononitrile and triethyl phosphite was also studied
under the same reaction conditions. However, the results were not
as positive as those presented above.
In our initial study, evaluation of different types of surfactants
was carried out for the tandem Knoevenagelephospha-Michael
reaction of 4-methoxybenzaldehyde, malononitrile, and triethyl
phosphite in aqueous media. The results of these studies are
summarized in Table 1.
Furthermore, we have evaluated the generality of the presented
method for the one-pot synthesis of b-phosphonomalonates from
different in situ generated Michael acceptors and trialkyl phos-
phites (Table 3).
Table 1
Tandem Knoevenagelephospha-Michael reaction of 4-methoxybenzaldehyde, ma-
lononitrile, and triethyl posphite under different conditions
As is obvious from Table 3, the catalytic one-pot reaction of
4-chlorobenzaldehyde and malononitrile proceeded well with tri-
alkyl phosphites, such as triethyl/trimethyl/tri-iso-propyl phos-
phite (entries 1e3). These results demonstrate that both the yields
and the reaction times are relatively independent of the phos-
phorus compounds. In addition to malononitrile, some other in situ
generated Michael acceptors were also examined to carry out the
reaction with triethyl phosphite (entries 4e6). The results showed
that the reaction involving ethyl cyano acetate worked well and the
desired product was obtained in 73% yield. However, no product
was produced when diethyl malonate or nitromethane were used
in this one-pot reaction under the same conditions.
Entry
Surfactant
Amount (CMC)
T (ꢀC)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
CTAB
Triton X-100
SDS
1
1
1
1
80
80
80
80
80
80
80
60
40
rt
10
7
2
2
1
1
1
1
1
70b
60b
70c
75
85
84
85
65
50
Sodium stearate
Sodium stearate
Sodium stearate
Sodium stearate
Sodium stearate
Sodium stearate
Sodium stearate
d
5
15
25
5
5
5
d
9
10
11
1
24
50
80
60c
a
It should be noted that no competitive side reactions, such as the
Isolated yield, conditions: aldehyde (1 mmol), malononitrile (1 mmol), triethyl
phosphite (1 mmol).
formation of
transformations. These observations prompted us to study the
possibility of the formation of -hydroxyphosphonate as an
a-hydroxyphosphonates were observed in these
b
The yield of the product remained constant after 24 h.
A mixture of by-products besides the desired product was formed.
c
a
intermediate in these reactions. We have found that the treatment
of 4-methoxybenzaldehyde with triethyl phosphite in micellar
solution of sodium stearate in aqueous media at 80 ꢀC did not
As shown in Table 1, surfactants, such as cetyltrimethy-
lammonium bromide(CTAB) as a cationicmicelle and Triton X-100 as
a neutral micelle at their critical micellar concentrations (CMC)
in water produced the desired product in 70 and 60% yields,
respectively (entries 1 and 2). A drastic rate enhancement was ob-
served when the reaction was performed in a micellar solution of
sodium dodecyl sulfate (SDS) (entry 3). The yield of the product
increased by using sodium stearate (entry 4) as the result of
increasing surfactivity by lengthening of sodium stearate hydrocar-
bon chain compared with SDS. The required amount of sodium
stearate for this reaction was also evaluated. It was found that when
increasing the amount of sodium stearate from 1 to 5, 15, and
25 CMCs, the yields increased from 70 to 85% (entries 5e7). Thus,
using a micellar solution of sodium stearate with 5 CMC in water is
sufficient to push this reaction forward. Larger amounts of the sur-
factant did not improve the yields. In order to optimize the reaction
temperature, the reaction was carried out at different temperatures
ranging from room temperature to 80 ꢀC (entries 8e10). Within the
tested temperatures, 80 ꢀC was found to be the mostsuitable reaction
temperature. Further studies showed that the presence of sodium
stearate in this reaction is crucial, such that the similar reaction in the
absence of sodium stearate led to the formation of the desired
product in 60% yields besides a mixture of side products (entry 11).
After optimization of the reaction conditions, to delineate
this approach, particularly in regard to library construction,
this methodology was evaluated for the synthesis of different
produce any significant amount of the corresponding
a-hydrox-
yphosphonate even after 24 h (IR, NMR, MS).
We have also studied the initial Knoevenagel reaction for the
a,b-unsaturated malonate formation as the intermediate from the
reaction of 4-methoxybenzaldehyde and malononitrile. The desired
a,b-unsaturated malonate was isolated in 89% yield after 10 min in
micellar solution of sodium stearate in aqueous media at 80 ꢀC.
These observations delineate the tandem Knoevenagelephos-
pha-Michael reaction for the synthesis of b-phosphonomalonates in
the micellar solution of sodium stearate. Thus, Knoevenagel
reaction between the aldehydes and malononitrile produce an ini-
tial a,b-unsaturated malonate. Subsequent phospha-Michael addi-
tion of trialkyl phosphites then leads to the formation of the desired
products. It is noteworthy to mention that reports on the synthesis
of b-phosphonomalonates are mainly focused on the two-pot pro-
cedures and the report for the one-pot synthesis of these com-
pounds directly from simple and readily available starting materials
is rare in the literature.5i
The catalytic effect of micellar solution of sodium stearate in
these reactions can be explained as follows: aldehyde, malononi-
trile, and trialkyl phosphite are hydrophobic molecules in aqueous
media. In the micellar solution of sodium stearate, the hydrophobic
moieties escape away from water molecules, which encircle the
micelle core of sodium stearate and forced inside the hydrophobic

3542
S. Sobhani, Z.P. Parizi / Tetrahedron 67 (2011) 3540e3545
Table 2
Synthesis of different
b
-phosphonomalonates via tandem Knoevenagelephospha-Michael reaction in solution of sodium stearate in water
O
(EtO)2P
CN
CN
R
H
CN
CN
sodium stearate, H2O
5 CMC, 80 ºC
P(OEt)3
O
+
+
R
1-11
R = aryl, heteroaryl, alkyl
Aldehyde
Entryref
15f,14a
Product
Time (h)
1
Yielda (%)
85
CHO
O
CN
CN
(EtO)2P
MeO
MeO
1
214c
2
85
O
Cl
CN
CN
(EtO)2P
CHO
Cl
2
3
3
84
86
O
Br
CHO
CHO
CN
CN
(EtO)2P
Br
3
45f,14a
5.5
O
CN
CN
(EtO)2P
Me
Me
4
5
3
82
CHO
O
CN
CN
(EtO)2P
Br
Cl
Br
5
65f
3
3
83
91
CHO
CHO
O
CN
CN
(EtO)2P
Cl
6
75f,14a
O
CN
CN
(EtO)2P
Cl
Cl
7
814a,b
2
80
O
CHO
CN
CN
(EtO)2P
O
O
8

S. Sobhani, Z.P. Parizi / Tetrahedron 67 (2011) 3540e3545
3543
Table 2 (continued )
Entryref
9
Aldehyde
CHO
Product
Time (h)
1
Yielda (%)
89
O
CN
CN
(EtO)2P
N
N
9
10
11
a
2
4
85
81
CHO
O
CN
CN
(EtO)2P
10
O
CHO
CN
CN
(EtO)2P
11
Isolated yield, conditions: aldehyde (1 mmol), malononitrile (1 mmol), triethyl phosphite (1 mmol), 80 ꢀC, aqueous solution of sodium stearate (4 mL, 5 CMC). All the
products were characterized by spectroscopic methods and compared with the authentic spectra.5f,14
and triethyl phosphite in the presence of a catalytic amount of
HClO4eSiO2, metal oxides [e.g., TiO2, CdO, CuO, Sb2O3, SnO2, ZnO]
and Brønsted acids [e.g., NH2SO3H and H3PMo12O40] (Table 4). As is
evident from Table 4, the micellar solution of sodium stearate is the
most effective catalyst for this purpose leading to the formation of
Table 3
One-pot synthesis of b-phosphonomalonates from different in situ generated Mi-
chael acceptors and trialkyl phosphites in micellar solution of sodium stearate in
water
O
b-phosphonomalonate (1) in good yield.
X
Y
(R'O)2P
CHO
+
X
Y
Table 4
sodium stearate, H2O
5 CMC, 80 ºC
P(OR')3
+
Comparison of the catalytic efficiency of micellar solution of sodium stearate with
various catalysts
Cl
Entry
Catalyst
Time (h)
Yielda (%)
Cl
1
2
3
4
5
6
7
8
9
Sodium stearate
HClO4eSiO2
TiO2
CdO
CuO
Sb2O3
SnO2
ZnO
NH4SO3H
H3PMo12O40
1
24
24
24
24
24
24
24
24
24
85
28
10
25
20
5
18
15
5
Entryref
Rꢁ
X
Y
Time (h)
Yielda (%)
1 5f,5a,a
214a
315
45f
5
6
Et
CN
CN
CN
CN
CO2Et
H
CN
CN
CN
CO2Et
CO2Et
NO2
3
1
2
1
24
24
91
82
80
73b
0
Me
i-Pr
Et
Et
Et
0
a
Isolated yield, 4-chlorobenzaldehyde (1 mmol), active methylene group
(1 mmol), trialkyl phosphite (1 mmol), 80 ꢀC, aqueous solution of sodium stearate
(4 mL, 5 CMC). All the products were characterized by spectroscopic methods and
compared with the authentic spectra.5f,14a,15
10
0
a
Isolated yield, conditions: catalyst (0.008 mmol), 4-methoxybenzaldehyde
(1 mmol), malononitrile (1 mmol), triethyl phosphite (1 mmol), H2O (4 mL), 80 ꢀC.
b
dr¼50:50, according to NMR.
3. Conclusions
core of the micelle droplets, where the reactions take place more
easily. This explanation is schematically presented by Fig. 1.
In order to show the unique catalytic behavior of the micellar
solution of sodium stearate in these reactions, we have performed
the one-pot reaction of 4-methoxybenzaldehyde, malononitrile,
In conclusion, we have successfully developed a simple one-pot
protocol to generate phosphorusecarbon bonds via a tandem
Knoevenagelephospha-Michael reaction in aqueous micellar so-
lution of sodium stearate. This simple procedure allows a series of
b-phosphonomalonates to be synthesized from the reaction of aryl/
heteroaryl/alkyl aldehydes, malononitrile, and trialkyl phosphites.
H2O
H2O
4. Experimental section
4.1. General
H2O
O
H2O
H2O
H2O
H2O
P(OR')3
(R'O)2P
CN
CN
H2O
R
H
O
CN
R
H2O
Chemicals were purchased from Merck and Fluka Chemical
Companies. NMR spectra were recorded in parts per million in
CDCl3 on a Bruker Avance DPX-250 instrument using TMS as
internal standard. Mass spectra were recorded on a Shimadzu
GCeMS-QP5050A. Elemental analysis for C, H, and N were obtained
using an Elementar, Vario EL III. The purification of the products
and the progress of the reactions were accomplished by TLC on
silica-gel polygram SILG/UV254 plates.
CN
H2O
H2O
H2O
Hydrophilic core
Hydrophobic core
Fig. 1. The proposed pole of micellar sodium stearate droplets for the synthesis of
different types of -phosphonomalonates via Knoevenagelephospha-Michael reaction.
b

3544
S. Sobhani, Z.P. Parizi / Tetrahedron 67 (2011) 3540e3545
4.2. Reaction procedures and spectral data
(m, 1H), 4.03e4.26 (m, 3H), 4.56 (dd, 1H, 3JHH¼8.0 Hz, 3JHP¼9.2 Hz),
7.41e7.45 (m, 3H), 7.50 (s, 1H).
Aldehyde (1 mmol), malononitrile (1 mmol), and triethyl
phosphite (1 mmol) was added to a micellar solution of sodium
stearate (4 mL, 0.002 M) in water. The mixture was stirred for an
appropriate time at 80 ꢀC (Table 1). The solvent was evaporated
under reduced pressure to give a crude product. Pure product was
obtained by column chromatography eluted with n-hexane/EtOAc
(1:1/1:2).
4.2.7. [1-(4-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl
ester (7). Yield 0.30 g, 91%; yellow solid, mp 98 ꢀC; Rf (50% n-hex-
ane/EtOAc) 0.53; dH (250 MHz, CDCl3) 1.16 (t, 3H, 3JHH¼7.0 Hz), 1.33
3
3
2
(t, 3H, JHH¼7.0 Hz), 3.62 (dd, 1H, JHH¼7.5 Hz, JHP¼21.5 Hz),
3
3.82e4.19 (m, 4H), 4.55 (t, 1H, JHH¼7.7 Hz), 7.42 (s, 4H).
4.2.8. [1-(Furan-2-yl)-2,2-dicyanoethyl] phosphonic acid diethyl es-
ter (8). Yield 0.23 g, 80%; dark yellow liquid; Rf (50% n-hexane/
EtOAc) 0.42; dH (250 MHz, CDCl3) 1.24e1.37 (m, 6H), 3.87 (dd, 1H,
4.2.1. [1-(4-Methoxy)-2,2-dicyanoethyl] phosphonic acid diethyl es-
ter (1). Yield 0.27 g, 85%; yellow solid, mp 61 ꢀC; Rf (50% n-hexane/
3
2
EtOAc) 0.50; dH (400 MHz, CDCl3) 1.17 (t, 3H, JHH¼7.2 Hz), 1.37 (t,
3JHH¼6.5 Hz, JHP¼22.7 Hz), 3.98e4.23 (m, 4H), 4.51 (t, 1H,
3
3
2
3H, JHH¼7.2 Hz), 3.57 (dd, 1H, JHH¼8.0 Hz, JHP¼21.2 Hz), 3.84 (s,
3JHH¼8.7 Hz), 6.44 (s, 1H), 6.62 (s, 1H), 7.49 (s, 1H).
3
3
3H), 4.00e4.24 (m, 4H), 4.51 (dd, 1H, JHH¼8.0 Hz, JHP¼8.8 Hz),
3
6.97 (d, 2H, JHH¼8.8 Hz), 7.41e7.44 (m, 2H).
4.2.9. [1-(Pyridin-3-yl)-2,2-dicyanoethyl] phosphonic acid diethyl
ester (9). Yield 0.26 g, 89%; dark orange liquid; [Found: C, 52.71; H,
5.32; N, 14.04. C13H16N3O3P requires C, 53.24; H, 5.50; N, 14.33%]; Rf
4.2.2. [1-(2-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl
ester (2). Yield 0.28 g, 85%; yellow solid, mp 77 ꢀC; Rf (50% n-hex-
ane/EtOAc) 0.57; dH (400 MHz, CDCl3) 1.11 (t, 3H, 3JHH¼7.0 Hz), 1.36
(50% n-hexane/EtOAc) 0.07; ymax (KBr) 2236 (CN),1011 (P]O) cmꢂ1
;
dH (250 MHz, CDCl3) 1.18 (t, 3H, 3JHH¼6.8 Hz),1.33 (t, 3H, 3JHH¼7.0Hz),
3.65 (dd, 1H, 3JHH¼6.8 Hz, 2JHP¼21.6 Hz), 3.92e4.21 (m, 4H), 4.63 (t,
1H, 3JHH¼8.5 Hz), 7.39 (t, 1H, 3JHH¼6.5 Hz), 7.95 (d, 1H, 3JHH¼6.5 Hz),
3
3
(t, 3H, JHH¼7.0 Hz), 3.75e4.30 (m, 4H), 4.46 (dd, 1H, JHH¼8.2,
1JHP¼21.2 Hz), 4.61 (t, 1H, 3JHH¼8.5 Hz), 7.35 (d, 2H, 3JHH¼4 Hz), 7.47
(s, 1H), 7.75 (d, 1H, 3JHH¼5.3 Hz).
3
8.67 (s, 2H); dC (62.9 MHz, CDCl3) 16.1 (d, JCP¼5.0 Hz), 16.2 (d,
3JCP¼5.0 Hz), 25.3, 42.1 (d, 1JCP¼144.6 Hz), 63.8 (d, 2JCP¼7.0 Hz), 64.5
(d, 2JCP¼7.0 Hz), 110.8 (d, 3JCP¼10.7 Hz), 111.0 (d, 3JCP¼11.9 Hz), 124.0,
126.7, 136.5, 150.5, 150.8; dP (101 MHz, CDCl3) 19.03; m/z (EI, 70 eV)
293 (10 Mþ), 156 [100 MþꢂP(O)(OEt)2], 138 (92), 130 (25), 111 (98%).
4.2.3. [1-(3-Bromophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl
ester (3). Yield 0.31 g, 84%; white solid, mp 78e79 ꢀC; [Found: C,
44.33; H, 4.12; N, 7.39. C14H16BrN2O3P requires C, 45.30; H, 4.34; N,
7.55%]; Rf (50% n-hexane/EtOAc) 0.46; ymax (KBr) 2242 (CN), 1003
(P]O) cmꢂ1
;
dH (400 MHz, CDCl3) 1.14 (t, 3H, 3JHH¼7.2 Hz), 1.31 (t,
4.2.10. [1,1-Dicyanopentan-2-yl] phosphonic acid diethyl ester
(10). Yield 0.22 g, 85%; yellow liquid; [Found: C, 51.07; H, 7.12; N,
10.46. C11H19N2O3P requires C, 51.16; H, 7.42; N, 10.85%]; Rf (50% n-
3
3
2
3H, JHH¼7.2 Hz), 3.65 (dd, 1H, JHH¼7.6 Hz, JHP¼21.6 Hz),
3.81e4.19 (m, 4H), 4.7 (dd,1H, 3JHH¼8.0 Hz, 2JHP¼9.2 Hz), 7.28 (t,1H,
3JHH¼8.0 Hz), 7.44 (d, 1H, JHH¼7.2 Hz), 7.52 (d, 1H, JHH¼8.0 Hz),
hexane/EtOAc) 0.5; ymax (KBr) 2240 (CN), 1011 (P]O) cmꢂ1
; dH
3
3
3
7.62 (s, 1H); dC (100 MHz, CDCl3) 16.1 (d, JCP¼5.0 Hz), 16.2 (d,
(250 MHz, CDCl3) 1.00 (t, 3H, 3JHH¼7.0 Hz), 1.37 (t, 6H, 3JHH¼7.0 Hz),
3
3JCP¼6.0 Hz), 25.3, 43.8 (d, 1JCP¼143.0 Hz), 63.6 (d, 2JCP¼7.0 Hz), 64.4
(d, 2JCP¼7.0 Hz), 111.3 (d, 3JCP¼12.1 Hz), 111.4 (d, 3JCP¼11.1 Hz), 123.1,
127.9 (d, 3JCP¼6.0 Hz), 130.8, 132.4 (d, 2JCP¼6.0 Hz), 132.6, 132.8 (d,
3JCP¼6.0 Hz); m/z (EI, 70 eV) 370 (22 Mþ), 372 (22 Mþþ2), 207 (80),
209 (80), 138 (100%).
1.61 (q, 2H, JHH¼7.0 Hz), 1.73e2.10 (m, 2H), 2.29e2.34 (m, 1H),
4.16e4.25(m, 4H), 4.29e4.35 (m,1H); dC (62.9 MHz, CDCl3) 13.73,16.3
3
2
(d, JCP¼5.6 Hz), 20.7 (d, JCP¼7.6 Hz), 29.2, 37.8 (d, 1JCP¼144.9 Hz),
110.7 (d, 3JCP¼5.0 Hz), 112.2 (d, 3JCP¼17.0 Hz); m/z (EI, 70 eV) 259 (4
Mþþ1), 138 (100) 121 [20 MþꢂP(O)(OEt)2], 111 (72), 95 (6%).
4.2.4. [1-(4-Methyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester
4.2.11. [1,1-Dicyanooctan-2-yl] phosphonic acid diethyl ester
(11). Yield 0.24 g, 81%; yellow liquid; [Found: C, 55.36; H, 8.03; N 9.20.
C14H25N2O3P requires C, 55.99; H, 8.39; N, 9.33%]; Rf (50% n-hexane/
(4). Yield 0.26 g, 86%; yellow solid, mp 97 ꢀC; Rf (50% n-hexane/
3
EtOAc) 0.44; dH (400 MHz, CDCl3) 1.16 (t, 3H, JHH¼7.2 Hz), 1.38 (t,
3
3
3H, JHH¼7.2 Hz), 2.40 (s, 3H), 3.57 (dd, 1H, JHH¼8.0 Hz,
EtOAc) 0.6; ymax (KBr) 2238 (CN), 1011 (P]O) cmꢂ1
; dH (400 MHz,
2JHP¼21.2 Hz), 3.74e3.84 (m, 1H), 3.99e4.06 (m, 1H), 4.14e4.25 (m,
CDCl3) 0.81 (t, 3H, JHH¼6.8 Hz), 1.23e1.25 (m, 6H), 1.29 (t, 6H,
3
3
3
2H), 4.50 (dd, 1H, JHH¼8.4 Hz, JHP¼9.0 Hz), 7.25e7.29 (m, 2H),
7.37e7.39 (m, 2H).
3JHH¼7.2 Hz), 1.45e1.50 (m, 2H), 1.66e1.79 (m, 1H), 1.86e1.98 (m, 1H),
3
2.25e2.34 (m, 1H), 4.08e4.16 (m, 4H), 4.36 (dd, 1H, JHP¼13.2 Hz,
3
3JHH¼3.6 Hz); dC (62.9 MHz, CDCl3) 13.9, 16.21 (d, JCP¼5.0 Hz), 22.3,
4.2.5. [1-(4-Bromophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl
ester (5). Yield 0.30 g, 82%; white solid, mp 102 ꢀC; [Found: C,
44.46; H, 4.15; N, 7.39. C14H16BrN2O3P requires C, 45.30; H, 4.34; N,
7.55%]; Rf (50% n-hexane/EtOAc) 0.44; ymax (KBr); 2242 (CN), 1000
23.7, 27.1, 27.2 (d, 3JCP¼6.0 Hz), 28.8, 31.2, 37.7 (d,1JCP¼143.0 Hz), 63.1 (d,
2JCP¼7.0 Hz), 111.1 (d, 3JCP¼3.0 Hz),112.3 (d, 3JCP¼17.0 Hz); m/z(EI, 70 eV)
301 (1 Mþþ1), 163 [18 MþꢂP(O)(OEt)2], 138 (100), 111 (76), 81 (77%).
(P]O) cmꢂ1
;
dH (250 MHz, CDCl3) 1.16 (t, 3H, 3JHH¼7.0 Hz), 1.33 (t,
4.2.12. [1-(4-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid di-
methyl ester. Yield 0.25 g, 82%; white solid, mp 118 ꢀC; Rf (50% n-
hexane/EtOAc) 0.31; dH (400 MHz, CDCl3) 3.61e3.68 (m, 4H), 3.86
(d, 3H, 3JHP¼11.2 Hz), 4.51 (t, 1H, 3JHH¼8.0 Hz), 7.50 (s, 4H).
3
3
2
3H, JHH¼7.0 Hz), 3.58 (dd, 1H, JHH¼7.5 Hz, JHP¼21.5 Hz),
3
3.79e4.18 (m, 4H), 4.56 (t, 1H, JHH¼7.75 Hz), 7.36 (d, 2H,
3JHH¼8.25 Hz), 7.56 (d, 2H, 3JHH¼8.0 Hz); dC (62.9 MHz, CDCl3) 16.1
(d, 3JCP¼4.4 Hz), 16.2 (d, 3JCP¼5.7 Hz), 25.4, 43.9 (d, 1JCP¼144.7 Hz),
2
2
3
63.6 (d, JCP¼7.5 Hz), 64.4 (d, JCP¼7.5 Hz), 111.0 (d, JCP¼11.9 Hz),
4.2.13. [1-(4-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid di-
iso-propyl ester. Yield 0.28 g, 80%; yellow solid, mp 111 ꢀC; Rf (50%
n-hexane/EtOAc) 0.62; dH (400 MHz, CDCl3) 1.00 (d, 3H,
3
111.2 (d, JCP¼10.7 Hz), 123.9, 129.4, 131.0, 132.5; dP (101 MHz,
CDCl3) 19.27; m/z (EI, 70 eV) 370 (7 Mþ), 372 (8 Mþþ2), 233 [12
MþꢂP(O)(OEt)2], 235 [12 (Mþþ2)ꢂP(O)(OEt)2], 207 (100), 209 (99),
138 (66%).
3
3
3JHH¼6.4 Hz), 1.32 (d, 3H, JHH¼6.0 Hz), 1.39 (d, 6H, JHH¼6.0 Hz,),
3
2
3.51 (dd, 1H, JHH¼7.2 Hz, JHP¼21.6 Hz), 4.51e4.57 (m, 1H),
4.75e4.83 (m, 1H), 7.43e7.50 (m, 4H).
4.2.6. [1-(3-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl
ester (6). Yield 0.27 g, 83%; yellow liquid; Rf (50% n-hexane/EtOAc)
4.2.14. [1-(4-Chlorophenyl)-2-cyano-2-ethylcarboxylic acid ethyl es-
ter] phosphonic acid diethyl ester. Yield 0.27 g, 73%; light yellow
liquid; Rf (50% n-hexane/EtOAc) 0.46; dH (400 MHz, CDCl3)
3
0.56; dH (400 MHz, CDCl3) 1.20 (t, 3H, JHH¼7.2 Hz), 1.38 (t, 3H,
3
2
3JHH¼7.2 Hz), 3.60 (dd, 1H, JHH¼8.0 Hz, JHP¼21.2 Hz), 3.83e3.93

S. Sobhani, Z.P. Parizi / Tetrahedron 67 (2011) 3540e3545
3545
3
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1.10e1.15 (m, 2H), 1.19e1.30 (m, 6H), 1.35 (t, 1H, JHH¼7.2 Hz),
3
3.74e3.85 (m, 1H), 3.96e4.21 (m, 6H), 4.27 (dd, 1H, JHH¼6.0 Hz,
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Acknowledgements
We are thankful to Birjand University Research Council for their
support on this work.
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