P-C bond formation via direct and three-component conjugate addition catalyzed by ZnO nano-rods for the synthesis of 2-oxindolin-3-yl-phosphonates under solvent-free conditions

Article abstract of DOI:10.1039/c2nj20947k

A simple and novel method is reported for the synthesis of 2-oxindolin-3-yl-phosphonates using ZnO nano-rods as a catalyst under solvent-free conditions at room temperature. ZnO nano-rods are synthesized successfully by employing Zn(OAc)₂·2H

Full text of DOI:10.1039/c2nj20947k

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PAPER
P–C bond formation via direct and three-component conjugate
addition catalyzed by ZnO nano-rods for the synthesis of
2-oxindolin-3-yl-phosphonates under solvent-free conditions
Mona Hosseini-Sarvari* and Mina Tavakolian
Received (in Montpellier, France) 9th November 2011, Accepted 27th January 2012
DOI: 10.1039/c2nj20947k
A simple and novel method is reported for the synthesis of 2-oxindolin-3-yl-phosphonates using
ZnO nano-rods as a catalyst under solvent-free conditions at room temperature. ZnO nano-rods
are synthesized successfully by employing Zn(OAc)2Á2H2O, NH3 and polyethylene glycol
(PEG , Mw = 2000). X-Ray diffraction (XRD), scanning electron microscopy (SEM),
transmission electron microscopy (TEM), and BET surface measurement were used to
characterize the structure and morphology of the catalyst.
the nature of the catalyst, tedious workup is needed. Additionally,
in most of these methods, poisonous trialkyl phosphite was used
as the phosphorus nucleophile.
Introduction
The search for new highly effective synthetic methods and
procedures is a key strategic direction in the development of
science and technology.1 In this context, the creation of new
processes of selective chemical bond formation and cleavage is
an important goal of modern organoelement chemistry.2,3
Special attention is devoted to the reaction of highly effective
synthetic methods for preparation of organophosphorus
compounds. The versatile nature of phosphorus allows it to
play a major role in modern synthetic chemistry.4 Phosphonates
and phosphorus ylides are important synthetic intermediates
used in Wittig and related reactions.5
Interestingly, coupling of P–C and C–C bond forming
events during phospha-Michael addition represents a challenge
in organophosphorus synthesis.15 As part of our ongoing
research on phosphonates, we envisioned that the development
of a modular protocol that would involve tandem P–C/C–C
bond formation would be useful for the combinatorial synthesis
of diversified 2-oxindolin-3-yl-phosphonates via condensation
reaction of isatins, malononitrile and dialkyl phosphonates in
single operation (Scheme 1).
A detailed literature survey towards the synthesis of
2-oxindolin-3-yl-phosphonates revealed that only few papers
have been published.16 These methods have limitations such as
low yields, long reaction times, and high temperatures. In
particular, these methods were not multi-component reactions
and use of a Knoevenagel adduct as starting material was
required.16b Thus it is necessary to develop an efficient and
convenient method for the synthesis of such significant scaffolds.
ZnO as a semi-conducting material is one of the popular
oxides based on its electrical, optical and catalytic properties.
ZnO based materials have found a wide range of applications in
solar cells, transparent conducting films, ultraviolet-protection
films, chemical sensors, light emitting diodes, laser diodes, catalysis
and so forth.17–19
Phosphonoformates have shown activity in cell cultures
against HPTLV-III (the virus implicated in AIDS).6 Amino
phosphonates have been intensively studied as stable transition state
analogues and enzyme inhibitors.7 Natural products containing
P–C bonds also show interesting biological activities.8 There-
fore, organophosphorus compounds have found a wide range
of applications in the areas of industrial, agricultural, and
medicinal chemistry. Among various methods to generate P–C
bonds, the conjugate addition of phosphorus nucleophiles to
activated alkenes (phospha-Michael reaction) holds a fundamental
position in organophosphorus compounds chemistry.9 This kind of
phosphorus carbon bond formation is most commonly promoted
by bases,10 Brønsted/Lewis acids,11 microwaves,12 transition
metals,13 and radical initiators such as AIBN.14 Although
phospha-Michael addition could proceed by these methods,
many of these methods suffer from one or more of the following
drawbacks, such as: reagents cannot be re-used, long reaction
times, drastic reaction conditions and sometimes, according to
In recent years, ZnO nano-rods have received extensive attention
in the fabrication of nanodevices. One of the important parameters
of ZnO nano-rods is its size and morphology. It is very crucial
Department of Chemistry, Shiraz University, Shiraz 71454,
I. R. Iran. E-mail: hossaini@shirazu.ac.ir; Fax: 0098 711 2284822;
Tel: 0098 711 2286006
Scheme 1 Tandem C–C/P–C bond forming approach.
c
1014 New J. Chem., 2012, 36, 1014–1021
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Scheme 2 Synthesis of 2-oxindolyl-3-yl-phosphonate catalyzed by
ZnO nano-rods.
to control the morphology of ZnO for use in nanophotonic
devices.20,21
Now in this article, we want to report the use of ZnO nano-
rods (o20 nm) as an efficient catalyst for carbon–carbon and
carbon–phosphorus bonds formation via a direct and three-
component conjugate addition reaction under solvent-free and
room temperature conditions (Scheme 2). The first step in this
concept was the preparation and characterization of ZnO
nano-rods. This nanocatalyst can be easily prepared by using
PEG2000 and conventional heating in a very simple process
without use of any special devices from low cost chemical
sources with reproducible results and also its separation from
the reaction mixture is an easy task and not a time consuming
process. Use of ZnO nano-rods as a catalyst in organic
reactions is as yet limited to a few reports. N-Boc protection
reaction of a wide variety of amines catalyzed directly by ZnO
nano-rods has been reported in the literature.22 Recently, we have
reported the preparation and characterization of ZnO nano-flakes
and their applications in some organic transformations have been
investigated.10f,23 ZnO nano-rods are now reported as a practical,
inexpensive, and environmentally benign catalyst for the tandem
C–C and C–P bond formation in high yields.
Fig. 1 X-Ray diffraction plot of ZnO nano-rods.
Results and discussion
Fig. 2 SEM image of ZnO nano-rods.
Structural properties and characterization of ZnO nano-rods
X-Ray powder diffraction studies confirmed that the synthesized
materials were ZnO of the wurtzite phase. ZnO peaks in the XRD
pattern of the final product are (100), (002), (101), (102), (110),
(103), (112) appearing at 2y = 31, 34, 36, 47, 56, 63, and 681
respectively. No characteristic peaks from other impurities were
detected. XRD patterns of ZnO nano-rods are in good agreement
with the literature data (JCPDS file no. 36-1451). A defined line
broadening of the diffraction peaks is an indication that the
synthesized material is in the nanometre range. The crystallite
size was calculated from the Scherrer’s formula24 applied to the
major peak (y = 002) and was found to be around 20 nm. Fig. 1
shows the powder XRD pattern of the sample synthesized.
The surface morphologies of the ZnO nano-rods are shown
in Fig. 2 and 3. Fig. 2 shows the SEM image of the ZnO nano-rods
and Fig. 3 the TEM image of the ZnO nano-rods. These
demonstrate that the synthesized product is ZnO nano-rods and
the thickness of the wall of the rod is about 17 nm.
For further analysis of the synthesized catalyst, BET surface
area measurements were made by measuring N2 adsorption at
75 1C. The BET surface areas of the synthesized ZnO nano-rod
Fig. 3 TEM image of ZnO nano-rods.
studied the reaction of isatin 1a, malononitrile 2 and diethyl-
phosphite 3a as a model reaction (Table 1). We noticed that
the desired 2-oxindolin-3-yl-phosphonate 4a was produced in
80–98% yields by using different amounts of the catalyst under
solvent-free conditions at room temperature. As observed in
Table 1, entries 1–4, the addition of different amounts of the
catalyst are measured to be about 480 m2 gÀ1
.
Evaluation of catalytic activity of ZnO nano-rods
In order to ascertain or negate the role of ZnO nano-rods as
the catalyst and also the reproducibility of the results, we have
c
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Table 1 Condition screening of the reaction between isatin 1a
(1 mmol), malononitrile
(1.3 mmol)
Table 2 Comparison of catalytic activity of the ZnO nano-rod
catalyst with other nano and bulky ZnO and several other catalysts
for the synthesis of 4aa
2 (1 mmol), and diethylphosphite 3a
Crystal Surface area/ Time/ Yield of
size/nm m2 gÀ1
Entry Catalyst
min
3ab (%)
1
2
3
4
5
6
7
ZnO nano-rods 17–20
ZnO nano-flakes 20–30
480 Æ 0.6
60
98
70
75
20
40
Trace
Trace
380 Æ 0.8
250 Æ 0.6
2.5–12
10–40
—
100
200
210
240
190
150
Nano-MgO
Bulky ZnO
Bulky MgO
Bulky TiO2
Nano-TiO2
30–40
—
—
1000
122
Entry
Mol% of catalyst
Solvent
Time min
Yielda (%)
35
1
2
3
4
5
6
7
8
5
None
None
None
None
None
H2O
EtOH
EtOAc
Toluene
CH3CN
CHCl3
60
60
60
70
48 h
120
300
180
240
300
300
95
98
90
80
—
85
80
60
a
Reaction conditions: isatin (1 mmol), malononitrile (1 mmol),
diethylphosphite (1.3 mmol), catalyst (10 mol%, 0.008 g), solvent-free
10
25
50
Free
10
10
10
10
10
10
b
conditions, and room temperature. Isolated yield.
in terms of the size and the specific surface area of the catalyst
that also contribute in making the reaction more feasible due
to easy diffusion of reactants and product molecules. ZnO
nano-rods used in the present study are found to have large
surface area (480 m2 gÀ1), compared to the other nanometal
oxides. Also, the presence of the ZnO nano-rod appeared to be
essential not only for its basicity but also for the activation of
the P–H group. No reaction was observed when only a simple
base such as KOH was used.
9
10
11
10
Trace
Trace
a
Isolated yield.
ZnO nano-rod to the reaction mixture affects the yield of the
product noticeably. Moreover, in the absence of the ZnO
nano-rod catalyst, the desired product was not produced even
after 48 h. The effect of different solvents was also studied
(entries 6–11). The best result was observed under solvent-free
conditions. Probably, the ZnO nano-rod surface contributes to
the reaction so the solvents may be deactivated by the catalyst
decreasing the reaction yields. Apart from the environmentally
benign nature of the process under solvent-free conditions, the
desired product is highly soluble in warm EtOH, so the catalyst
can be easily separated from the organic phase by a simple
centrifugation procedure. We have applied this procedure for
the isolation and recycling of the catalyst for the semi-large
scale reaction of isatin, malononitrile and diethylphosphite.
For demonstrating the major role of ZnO nano-rods as a
catalyst, we have studied the reaction of isatin 1a, malononitrile 2
and diethylphosphite 3a by using a series of other metal oxides with
various particle sizes and the results are shown in Table 2. Nano-
flake ZnO, nano-TiO2, and nano-MgO were simply prepared in
our laboratory. Our studies showed that the ZnO nano-rod was an
efficient catalyst and exhibited the highest activity in comparison
with other metal oxides (both in bulk and nanosizes) in the
synthesis of compound 4a (Table 2, entries 1–7). The use of bulky
ZnO and MgO provided lesser yield, however, the use of TiO2
(both in bulk and nanosizes) did not exhibit any significant
catalytic effect (entries 4–7). The catalytic activity was observed
in the following order: ZnO nano-rods 4 ZnO nano-flakes, and
nano-MgO 4 bulky ZnO, and MgO 4 TiO2 with bulky and
nanodimensions.
With the preliminary success, the scope of this Knoevenagel
phospha Michael tandem process was studied by testing a wide
range of isatins with diverse substitution patterns and various
dialkyl and diphenyl phosphites. It should be emphasized that
in all cases, target compounds of type 4 were easily isolated
from the reaction mixture by a simple and green procedure,
thus satisfying our initial requirement for a synthetically useful
protocol (Table 3 and Scheme 2).
As it is obvious from Table 3, the catalytic phospha-Michael
addition of dialkyl or diphenyl phosphites with isatins containing
different electron-donating and electron-withdrawing groups
proceeded well and the desired products (4a–i) were obtained
in high yields (entries 1–9). In the reaction of (1b–e), the catalyst
was compatible with functional groups such as ÀNO2, ÀMe,
ÀCl, and ÀBr.
In order to examine the applicability of this method, the one-
pot, three-component reaction between isatin (1a), diphenyl-
phosphite (3a) and malononitrile was also studied (entry 9). It is
interesting to note that sterically hindered phenyl groups on the
phosphite moiety can also be converted to the desired 2-oxindolin-
3-yl-phosphonate 4i in good yield under these reaction conditions
albeit with longer reaction time.
To explore the potential of this catalytic system, we next
studied the reaction of ethyl cyanomalonate, which is less reactive
than malononitrile, with isatin and diethylphosphite under the
optimized conditions. The reaction worked well and the product
was isolated in good yield by using water as solvent (Scheme 3).
Apart from the mild conditions and environmentally benign
nature of the process and its excellent results, the simplicity of
product isolation and the possibility to recover and recycle
ZnO nano-rods as a catalyst offer significant advantages.
Because the desired products are soluble in EtOH, the catalyst
can be directly separated by a simple centrifugation procedure.
The catalyst after drying in an oven at 100 1C can directly be
reused. Studies using isatin and diethylphosphite as model
The activation of malononitrile 2 and the P(O)H group in
dialkylphosphite 3 is a prerequisite for the reaction. Generally,
metal oxides can activate malononitrile and the P(O)H group,
so deprotonation of the C–H and P–H bonds occurs much
better in the presence of stronger bases.10i Therefore, ZnO and
MgO were shown to be strongly better than TiO2 depending on
their basicity nature.25 The much greater activity of ZnO nano-
rods over ZnO nano-flakes and nano-MgO could be explained
c
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Table 3 Synthesis of 2-oxindol-3-yl-phosphonates using ZnO nano-rods (10 mol%) at room temperature under solvent-free conditions
Entry
Isatin 1
R3
Product 4
Time/min
Yielda (%)
1
Et
60
98
2
Et
45
98
3
4
5
Et
Et
Et
65
50
55
95
97
88
6
Et
50
45
92
97
7
8
1a
Me
1d
1a
Me
Ph
40
96
90
9
160
a
Isolated yield.
substrates showed that the recovered ZnO nano-rod could be
recycled five times (Table 4). XRD patterns, SEM, and TEM
images of solid ZnO nano-rods used in the reaction after 5th
recycling are shown in Fig. 4. According to the XRD pattern
no impurities were involved in the ZnO nano-rod, after 5th
recycling. In addition SEM and TEM of the recycled catalyst
c
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Scheme 3 Reaction of ethyl cyanomalonate with isatin and
diethylphosphite.
Table 4 Reuse ability of recovered ZnO nano-rodsa
Run
Isolated yield (%)
Recycle number
1
2
3
4
5
98
92
85
80
80
1
2
3
4
5
a
Reaction conditions: isatin (5 mmol), malononitrile (5 mmol),
diethylphosphite (6.5 mmol), catalyst (50 mol%, 0.04 g), solvent-free,
room temperature.
showed that the rods morphology and nanosize of the catalyst
were intact. However the yields of the products decreased
using the recycled catalyst (Table 4). This is perhaps due to the
adsorption of water molecules during work-up. The absorption
of water molecules by the catalyst has been demonstrated with
the FT-IR and TG analysis.
No attempt has been made to probe the mechanism of the
reaction. However, the proposed mechanism for the role of
ZnO nano-rod as a catalyst is shown in Scheme 4. In this
mechanism the formation of 2-oxindolin-3-yl-phosphonates 4
from the three-component reaction of isatin 1, malononitrile 2,
and dialkyl phosphite 3 was proposed to involve two steps:
(i) Knoevenagel condensation of the malononitrile anion with isatin
takes place with elimination of the hydroxide anion and formation
of isatylidenemalononitrile
5 followed by (ii) phospha-
Michael addition of dialkyl phosphate 3 to electron deficient
Knoevenagel adduct 5 leading to the corresponding 2-oxindolin-
3-yl-phosphonate product 4. The nano-ZnO has Lewis acid
(Zn2+) and Lewis basic (O2À) sites.26 In the first step (i) a Lewis
acid site (Zn2+) of nano-ZnO is coordinated to the oxygen of
the carbonyl group, resulting in the increased reactivity of
isatin.10f To argument with this step, Knoevenagel adduct 5
was isolated and characterized (IR, NMR, MS) when isatin
reacted with malononitrile in the presence of ZnO nano-rods
(10 mol%) at room temperature after a few minutes. In the
second step (ii), we proposed that a hydrogen bond from
the ÀOH groups on the surface of the catalyst activates the
Knoevenagel adduct. On the other hand the Lewis basic site of
ZnO NRs (O2À) coordinated to the phosphite form and then it
could attack the electrophilic CQC double bond. Regarding
the phosphorus nucleophile, in the presence of Lewis basic sites
of ZnO NRs (O2À), the actual nucleophilic species is the
phosphite 6 and not phosphonate 3 form.27
Fig. 4 (a) SEM image, (b) TEM image, and (c) XRD patterns of ZnO
nano-rods after 5th recycling reaction.
condensation by the P-Michael addition of dialkyl or diphenyl
phosphite to activated alkenes formed in situ. This unique
tandem C–C/P–C bond forming reaction allows the preparation
of diverse 2-oxindol-3-yl-phosphonates in single step. High yields,
short reaction times, use of dialkyl or diphenyl phosphate instead
of malodorous trialkyl phosphate, simple and green work-up, low
cost and easy recovery of the catalyst, no by-product formation,
room temperature, solvent free conditions and reusability of the
catalyst without appreciable loss of activity make this procedure
attractive and useful.
Conclusions
Studies on the other applications of this catalyst for the
related synthesis of isatin derivatives and also the other C–C
and C-heteroatom bond formation reactions are underway in
our laboratories.
In conclusion, we have developed a novel and practical reaction
sequence that enables the rapid assembly of medicinally relevant
phosphonate structures. The reaction involves a Knoevenagel
c
1018 New J. Chem., 2012, 36, 1014–1021
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Scheme 4 Proposed mechanism.
General procedure for the synthesis of 2-oxindolin-3-yl-phosphonates
Experimental section
1H NMR and 13C NMR spectra were measured on a Bruker
advance DPX FT 250 and 62.9 MHz spectrometer with
TMS as an internal standard. IR spectra were obtained on a
Perkin-Elmer or FTIR-800 instrument. Mass spectra were
obtained on a Shimadzu GCMS0QP 1000EX at 20 and/or
70 eV. Elemental analyses were performed on a Thermo
Finnigan, Flash EA 1112 series microanalyzer by the head
of the CHN lab. The catalyst was characterized by powder
X-ray diffraction (XRD) on a Bruker D8-advance X-ray
diffractometer with Cu Ka (l = 1.54178 A1) incident radiation.
The distribution morphology of the product was analyzed by
Leica Cambridge, model s360, version V03.03 scanning electron
microscopy (SEM) and transmission electron microscopy (Philips
CMIO TEM).
A mixture of isatin (1 mmol), dialkylphosphite (1.3 mmol),
malononitrile (1 mmol) and ZnO nano-rods (0.008 g, 10 mol%)
was stirred at room temperature several times. Upon completion,
the progress of the reaction was monitored by TLC and also by a
color change of the reaction mixture from orange to red and
when the reaction was completed with the color changing to
white, EtOH was added to the reaction mixture and the nano-rod
was separated by centrifugation. Then the solvent was removed
from solution under reduced pressure and the resulting product
purified by recrystallization using ethanol.
4a. White crystal mp 169–171 1C (ref. 11b 168–170 1C);
IR (KBr) (nmax/cmÀ1): 3124, 2877, 2260, 1735, 1620, 1249;
1H-NMR (250 MHz, DMSO-d6): d (ppm) 1.14 (t, J = 7.05
Hz, 3H, CH3), 1.25 (t, J = 7.05 Hz, 3H, CH3), 3.97–4.15
1
(m, 4H, CH2), 5.75 (d, JC–P = 8.00 Hz, 1H, CH(CN)2), 6.97
General procedure for the synthesis of the catalyst
(d, J = 7.75 Hz, 1H, ArH), 7.12 (t, J = 7.62 Hz, 1H, ArH),
7.33-7.30 (m, 1H, ArH), 7.54 (d, J = 7.50 Hz, 1H, ArH), 11.26
(s, 1H, NH); 13C NMR (62.9 MHz, DMSO-d6): 15.8, 26.9, 52.5
In a typical experiment for the synthesis of ZnO nano-rods
zinc acetate dihydrate Zn(OAc)2Á2H2O (1 g) and PEG 2000
(0.30 g) were dissolved in 140 ml deionized water at room
temperature to form a transparent solution. Then 1.5 ml
ammonium hydroxide NH4OH (25%) was added dropwise
to the solution. The mixture was refluxed for 6 h at 80 1C. It
was cooled by cold water to stop the reaction. The product
was centrifuged and washed with deionized water and absolute
ethanol. Then 90 ml deionized water was added and the
mixture was refluxed for 9 h. It was cooled by cold water,
centrifuged and washed. Then the ZnO nano-rod powders
were allowed to dry at 1001C in an oven for 3 h.
1
(d, JC–P = 138.5 Hz), 64.1, 64.8, 110.5, 121.4, 122.3, 125.6,
130.9, 143.0, 170.4; GC-MS/EI: m/z (%) = 333 [M+ = 21.4].
4b. Pale yellow crystal mp 187–190 1C (ref. 11b 185–190 1C);
IR (KBr) (nmax/cmÀ1): 3116, 2877, 2206, 1743, 1627, 1249;
1H-NMR (250 MHz, DMSO-d6): d (ppm) 1.22–1.34 (m, 6H,
3
CH3), 4.10–4.20 (m, 4H, CH2), 5.53 (d, JH–P = 7.40 Hz, 1H,
CH(CN)2), 7.10 (d, J = 8.7 Hz, 1H, ArH), 8.25 (t, J = 8.7 Hz,
1H, ArH), 8.45 (s, 1H, ArH), 11.60 (s, 1H, NH); 13C NMR
(62.9 MHz, DMSO-d6): 20.9, 31.65, 57.6 (d, 1JC–P = 138.6 Hz),
c
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69.7, 70.5, 115.7, 126.8, 127.3, 132.4, 147.9, 154.0, 154.2, 175.9;
GC-MS/EI: m/z(%) = 378 [M+ = 11.2].
7.47–7.57 (m, 2H, ArH), 11.55 (s, 1H, NH); 13C NMR
1
(62.9 MHz, DMSO-d6): 26.5, 52.4 (d, JC–P = 139.0 Hz), 54.6,
55.5, 111.07, 112.3, 123.2, 125.4, 126.4, 131.0, 141.9, 170.1 GC-MS/
EI: m/z(%) = 339 [M+ = 33.8]; anal. calcd. for C13H11ClN3O4P:
C, 45.97; H, 3.26%. Found: C, 45.86; H, 3.14%.
4c. White crystal mp 150–152 1C; IR (KBr) (nmax/cmÀ1):
3120, 3001, 2885, 2268, 1735, 1627, 1242; 1H-NMR (250 MHz,
DMSO-d6): d (ppm) 0.88–1.05 (m, 6H, CH3), 2.08 (s, 3H,
CH3), 3.77–3.91 (m, 4H, CH2), 5.62 (d, 3JH–P = 7.82 Hz, 1H,
CH(CN)2), 6.67 (d, J = 7.9 Hz, 1H, ArH), 6.98 (d, J = 7.22
Hz, 1H, ArH), 7.22 (s, 1H, ArH), 11.01 (s, 1H, NH); 13C NMR
(62.9 MHz, DMSO-d6): 14.9, 20.7, 27.0, 52.4 (d, 1JC–P = 138.7 Hz),
64.1, 64.8, 110.3, 11.4, 121.5, 126.1, 131.2, 131.5, 140.4, 170.4;
GC-MS/EI: m/z(%) = 347 [M+ = 12.6]; anal. calcd. for
C16H18N3O4P: C, 55.33; H, 5.22%. Found: C, 55.21; H, 5.15%.
4i. White crystal mp 170–172 1C (ref. 11b 165–168 1C); IR
(KBr) (nmax/cmÀ1): 3195, 940, 1727, 1620, 1262; 1H-NMR
3
(250 MHz, DMSO-d6): d (ppm) 6.82 (d, JH–P = 7.2 Hz, 1H,
CH(CN)2), 6.88–7.41 (m, 13H, ArH), 7.50 (d, J = 7.60 Hz,
1H, ArH), 11.43 (s, 1H, NH); 13C NMR (62.9 MHz,
1
DMSO-d6): 27.07, 75.5 (d, JC–P = 168 Hz), 110.6, 120.2,
120.7, 121.8, 125.2, 125.9, 126.5, 129.6, 130.5, 142.7, 150.2,
173.7 GC-MS/EI: m/z (%) = 429 [M+ = 15.3].
4d. White crystal mp 175–178 1C; IR (KBr) (nmax/cmÀ1):
3132, 2893, 2268, 1720, 1620, 1249; 1H-NMR (250 MHz,
DMSO-d6): d (ppm) 1.20–1.36 (m, 6H, CH3), 4.08–4.24
4j. White crystal mp 187–190 1C (ref. 11b 192–194 1C); IR
(KBr) (nmax/cmÀ1): 3120, 2870, 2260, 1717, 1622, 1254;
1H-NMR (250 MHz, DMSO-d6): d (ppm) 0.84 (t, J = 7.01
Hz, 3H, CH3), 1.12–1.21 (m, 6H, CH3), 3.84–3.87 (m, 2H,
CH2), À3.97–4.04 (m, 4H, CH2), 4.9 (d, 3JH–P = 7.45 Hz, 1H,
CH(CN)(CO2Et)), 6.86 (d, J = 7.80 Hz, 1H, ArH), 6.99–7.02
(m, 1H, ArH), 7.31–7.25 (m, 1H, ArH), 7.40 (d, J = 8.2 Hz,
3
(m, 4H, CH2), 5.8 (d, JH–P = 7.02 Hz, 1H, CH(CN)2), 7.01
(d, J = 8.37 Hz, 1H, ArH), 7.39–7.44 (m, 1H, ArH), 7.55 (s, 1H,
ArH), 11.41 (s, 1H, NH); 13C NMR (62.9 MHz, DMSO-d6):
1
15.7, 26.5, 53.4 (d, JC–P = 138.2 Hz), 64.2, 64.9, 110.1, 111.7,
121.2, 126.6, 130.5, 141.6, 170.1 (d, J = 3.0 Hz); GC-MS/EI: m/
z(%) = 367 [M+ = 31.4]; anal. calcd. for C15H15ClN3O4P: C,
48.99; H, 4.11%. Found: C, 48.87; H, 4.05%.
1H, ArH), 10.91 (s, 1H, NH); 13C NMR (62.9 MHz,
1
DMSO-d6): 13.3, 16.0, 24.5, 61.8, 63.1, 75.5 (d, JC–P
=
161.9 Hz), 110.3, 114.2, 121.4, 124.6, 126.0, 129.8, 142.5,
4e. White crystal mp 186–189 1C (ref. 11b 182–185 1C); IR
(KBr) (nmax/cmÀ1): 3150, 2890, 2254, 1723, 1620, 1254;
1H-NMR (250 MHz, DMSO-d6): d (ppm) 1.01–1.29 (m, 6H,
165.6, 174.8; GC-MS/EI: m/z(%) = 380 [M+ = 17.4].
5. Yellow powder mp 193–195 1C; IR (KBr) (nmax/cmÀ1):
3130, 2242, 2226, 1735, 1591; 1H-NMR (250 MHz,
DMSO-d6): d (ppm) 6.91 (d, J = 7.71 Hz, 1H, ArH), 7.10
(t, J = 7.602 Hz, 1H, ArH), 7.32–7.28 (m, 1H, ArH), 7.52
(d, J = 7.51 Hz, 1H, ArH), 11.01 (s, 1H, NH); 13C NMR
(62.9 MHz, DMSO-d6): 76.0, 113.2, 113.6, 110.5, 121.2, 122.5,
125.1, 127.4, 140.2, 170.2, 171.3; GC-MS/EI: m/z(%) = 195
[M+ = 25.8].
3
CH3), 3.90–4.10 (m, 4H, CH2), 5.17 (d, JH–P = 7.22 Hz, 1H,
CH(CN)2), 6.83 (d, J = 8.25 Hz, 1H, ArH), 7.41 (d, J = 8.1 Hz,
1H, ArH), 7.64 (s, 1H, ArH), 11.15 (s, 1H, NH); 13C NMR
1
(62.9 MHz, DMSO-d6): 15.6, 26.7, 52.5 (d, JC–P = 139.1 Hz),
64.3, 65.1, 110.1, 112.1, 114.1, 122.8, 128.4, 133.3, 142.0, 169.9
GC-MS/EI: m/z (%) = 411 [M+ = 8.3].
4f. White crystal mp 101–104 1C (ref. 11b 100–104 1C); IR
(KBr) (nmax/cmÀ1): 2985, 2931, 2206, 1720, 1612, 1257;
1H-NMR (250 MHz, DMSO-d6): d (ppm) 1.10 (t, J = 7.02
Hz, 3H, CH3), 1.21 (t, J = 7.01 Hz, 3H, CH3), 3.21 (s, 3H,
CH3), 3.94–4.15 (m, 4H, CH2), 5.93 (d, 3JH–P = 8.22 Hz, 1H,
CH(CN)2), 7.23 (m, 2H, ArH), 7.48–7.91 (m, 2H, ArH);
13C NMR (62.9 MHz, DMSO-d6): 15.8, 26.8, 26.9, 52.0
Acknowledgements
We thank the Shiraz University Research Council and Professor
A. Jarrahpour for his helpful editing of our manuscript.
1
(d, JC–P = 139.1 Hz), 64.2, 65.0, 109.8, 111.1, 111.4, 120.6,
Notes and references
123.2, 125.5, 131.0, 144.1 (d, J = 6.6), 168.9; GC-MS/EI: m/z
(%) = 347 [M+ = 7.9].
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3
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139.7 Hz), 54.8, 55.4, 110.7, 111.5, 121.3 (d, J = 5.7 Hz),
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3
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c
1020 New J. Chem., 2012, 36, 1014–1021
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