One-pot synthesis of β-phosphonomalonates catalyzed by molecular iodine

Article abstract of DOI:10.1080/00397911.2013.768670

A one-pot procedure has been developed for the synthesis of β-phosphonomalonates via P-C bond formation through tandem Knoevenagel-phospha-Michael reaction catalyzed by iodine as a new, inexpensive, nonmetallic, and commercially available catalyst. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]

Full text of DOI:10.1080/00397911.2013.768670

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One-Pot Synthesis of β-
Phosphonomalonates Catalyzed by
Molecular Iodine
Sara Sobhani a & Roya Jahanshahi
a Department of Chemistry, College of Sciences , University of
Birjand , Birjand , Iran
Published online: 05 Sep 2013.
To cite this article: Sara Sobhani & Roya Jahanshahi (2013) One-Pot Synthesis of β-
Phosphonomalonates Catalyzed by Molecular Iodine, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 43:24, 3247-3257
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Synthetic Communications1, 43: 3247–3257, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.768670
ONE-POT SYNTHESIS OF b-PHOSPHONOMALONATES
CATALYZED BY MOLECULAR IODINE
Sara Sobhani and Roya Jahanshahi
Department of Chemistry, College of Sciences, University of Birjand,
Birjand, Iran
GRAPHICAL ABSTRACT
Abstract A one-pot procedure has been developed for the synthesis of b-phosphonomalo-
nates via P-C bond formation through tandem Knoevenagel–phospha–Michael reaction
catalyzed by iodine as a new, inexpensive, nonmetallic, and commercially available catalyst.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Iodine; malononitrile; phosphites; b-phosphonomalonates; tandem reaction
INTRODUCTION
Within organophosphorous compounds, the synthesis of phosphonates has
evoked remarkable attention from organic chemists because of the biological activi-
ties and applications of phosphonates as enzyme inhibitors, metabolic probes,[1]
peptide mimetics,[2] antibiotics, and pharmacologic agents.[3] The most versatile
and powerful synthetic approach for the synthesis of phosphonates is direct phos-
phorus–carbon bond formation. Among the tools for P-C bond formation,
phospha-Michael addition is known as the most important routes.[4] Synthesis of
b-phosphonomalonates by this method is commonly promoted by Brønsted=Lewis
acids,[4g,4h] transition metals,[4i,4j] bases,[4a–f] microwave radiation,[4m] and radical
initiators.[4k,4l] Even though synthesis of b-phosphonomalonates could be proceeded
by these methods, they suffer from one or more of the following drawbacks, such as
long reaction time, drastic reaction conditions, and use of expensive catalyst. Some-
times, according to the nature of the catalyst, tedious workup is needed. Moreover,
Received October 13, 2012.
Address correspondence to Sara Sobhani, Department of Chemistry, College of Sciences,
University of Birjand, Birjand 414, Iran. E-mail: ssobhani@birjand.ac.ir, sobhanisara@yahoo.com
3247

3248
S. SOBHANI AND R. JAHANSHAHI
these methods proceed through a two-pot reaction in which P-C and C-C bond
formations occurred in separate steps. On the other hand, a literature survey
revealed that only a few papers have been published toward the one-pot synthesis
of b-phosphonomalonates.[5,6] Therefore, a new, simple, and efficient protocol for
the one-pot synthesis of such significant scaffolds is required.
Over the past few years, molecular iodine has emerged as a powerful catalyst
for various organic transformations.[7] Utilizing iodine is interesting for organic che-
mists, because iodine is a mild Lewis acid, cheap, readily available, less toxic than
alternatives, and moisture stable. Most of the reactions that are catalyzed by iodine
are associated with mild conditions, greater stereo- and regioselectivities, short reac-
tion times, and simplicity in their operation.
As part of our ongoing program on the development of new methods for the
phosphonates synthesis via P-C bond formation,[8] recently we have reported iodine
as an efficient nonmetallic catalyst for the synthesis of primary a-aminophospho-
nates.[9] Herein, we report iodine as a new catalyst for the synthesis of b-phosphono-
malonates by one-pot reaction of aldehydes, trialkyl phosphites, and malononitrile.
RESULTS AND DISCUSSION
At first, the reactions of benzaldehyde, malononitrile, and triethyl phosphite in
the presence of different amounts of iodine and at different temperatures were stud-
ied. The results of these studies are summarized in Table 1.
As depicted in Table 1, investigation of separate reactions in the presence of 5,
10, and 15 mol% of iodine under solvent-free conditions indicated that 10 mol% of this
catalyst was the best amount for this transformation at room temperature (entry 2).
The reason for the lower product yield in the presence of the greater amount of iodine
might be ascribed to the production of a sticky mixture, which in turn led to decreased
catalytic activity of iodine. Increase in reaction temperature (50 ꢀC) using 10 mol% of
iodine provided excellent product yield (entry 4). A similar reaction in the absence of
any amount of catalyst produced the desired product in poor yield after a long reaction
time at 50 ꢀC (entry 5). Solvent screening (entries 6–9) showed that the reaction
afforded maximum yield of the product under solvent-free conditions.
Table 1. Tandem Knoevenagel–phospha–Michael reaction of benzaldehyde,
malononitrile, and triethyl posphite under different conditions
Entry
I2 (mol%)
T (ꢀC)
Solvent
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
5
rt
rt
—
—
24
24
24
2
42
65
35
90
48
71
72
63
71
10
15
10
0
rt
—
—
50
50
50
50
50
50
—
24
6
10
10
10
10
n-Hexane
CH3CN
Toluene
CH2Cl2
3
4
4
aIsolated yield. Conditions: aldehyde (1 mmol), malononitrile (1 mmol), triethyl
phosphite (1 mmol).

SYNTHESIS OF b-PHOSPHONOMALONATES
3249
Scheme 1. One-pot synthesis of b-phosphonates catalyzed by iodine.
With these optimistic results in hand, the generality of the presented method
was evaluated for the one-pot synthesis of b-phosphonomalonates. For this reason
a range of various aldehydes were subjected to react with malononitrile and triethyl
phosphite in the presence of 10 mol% of iodine at 50 ꢀC under solvent-free conditions
(Scheme 1, Table 2).
As shown in Table 2, different substituted benzaldehydes with electron-donating
and electron-withdrawing groups underwent successful Knoevenagel–phospha–
Michael reaction with malononitrile and triethyl phosphite to produce the desired pro-
ducts in good to excellent yields (entries 1–8). Furan-2-carbaldehyde and pyridin-3-
carbaldehyde as acid-sensitive aldehydes underwent smooth reactions without any
decomposition or polymerization under the present reaction conditions (entries 9
and 10). Aliphatic aldehydes such as butyraldehyde and heptanal reacted with malo-
nonitrile and triethyl phosphite to afford the corresponding products in good yields
(entries 11 and 12). Synthesis of b-phosphonomalonates from the reactions of cinna-
maldehyde and crotonaldehyde as unsaturated aldehydes with malononitrile and
triethyl phosphite was also examined and no yields of the desired products were
obtained even after 48 h. The reactions of some ketones including cyclohexanone,
ethylmethyl ketone, and isatine were conducted under the present reaction conditions.
These reactions resulted in the recovery of the starting materials with a trace amount
of the corresponding products. It is worth noting that the phospha-Michael addition
of triethyl phosphite to a,b-unsaturated malonates of cyclohexanone, ethylmethyl
ketone, and isatine proceeded well in 1–3 h to afford the corresponding products
(13, 14, 15) in 65, 76, and 83% yields, respectively.
Noticeably, possible side reactions leading to a-hydroxyphosphonates were not
observed in all of these transformations. These observations encouraged us to exam-
ine the possibility of the formation of a-hydroxyphosphonate as an intermediate in
these reactions. For this purpose, the reaction of 4-chlorobenzaldehyde and triethyl
phosphite catalyzed by iodine at 50 ꢀC was studied and we found that no amount of
a-hydroxyphosphonate was not produced, even after 24 h.
Synthesis of b-phosphonomalonates through a one-pot reaction of aldehydes,
malononitrile, and triethyl phosphite was proposed to involve in a tandem
process. Aldehydes are activated by molecular iodine as a Lewis acid and undergo
Knoevenagel condensation with malononitrile to produce a,b-unsaturated malo-
nates. The resulting adducts are further activated by iodine to react with triethyl
phosphite via a phospha-Michael addition reaction (Scheme 2).
Occurrence of the initial Knoevenagel condensation reaction was confirmed by
the isolation of a,b-unsaturated malonate in 89% yield from the reaction of 4-chlor-
obenzaldehyde and malononitrile as a model reaction catalyzed by iodine at 50 ꢀC
after 15 min.

3250
S. SOBHANI AND R. JAHANSHAHI
Table 2. One-pot synthesis of different b-phosphonomalonates via tandem Knoevenagel–phospha–
Michael reaction catalyzed by iodine
Entry[ref]
Aldehyde
Product
Time (h)
Yielda (%)
1[6]
2
85
2[4f,6]
3
91
3[4f,6]
4[4f,6]
5[4f]
2
2
85
90
81
2.5
6[10]
1
82
95
7
8
2
2
82
(Continued )

SYNTHESIS OF b-PHOSPHONOMALONATES
Table 2. Continued
3251
Entry[ref]
Aldehyde
Product
Time (h)
Yielda (%)
9[11]
1
81
85
10
0.5
11
12
1
3
82
83
aIsolated yield. Conditions: aldehyde (1 mmol), malononitrile (1 mmol), triethyl phosphite (1 mmol),
iodine (10 mol%), 50 ꢀC, solvent-free conditions. All the products were characterized by spectroscopic
methods and compared with the authentic spectra.
Scheme 2. Suggested mechanism for one-pot reaction of aldehydes, malononitrile, and triethyl phosphite.

3252
S. SOBHANI AND R. JAHANSHAHI
Scheme 3. Synthesis of b-phosphonates from in situ–generated Michael acceptors and trialkyl phosphites.
Further investigations were carried out to explore the applicability of iodine as
a catalyst for the synthesis of b-phosphonomalonates from in situ–generated
Michael acceptors and trialkyl phosphites (Scheme 3, Table 3).
As indicated in Table 3, the catalytic one-pot reaction of 4-chlorobenzaldehyde
with malononitrile and trialkyl phosphites such as triethyl, trimethyl, and tri-iso-pro-
pyl phosphite worked well and the desired products were isolated in 95, 80, and 85%
yields, respectively (entries 1–3). However, no products were not obtained when
ethylcyanoacetate, diethyl malonate, nitromethane, ethylacetoacetate and Mel-
drum’s acid were employed as Knoevenagel donors instead of malononitrile under
the same reaction conditions (entries 4–8).
To show the unique catalytic behavior of iodine in the one-pot synthesis of b-
phosphonomalonates, the reaction of benzaldehyde, malononitrile, and triethyl
phosphite catalyzed by metal oxides such as CuO, Sb2O3, SnO2, HgO, MgO, and
CaO; Brønsted acids such as HClO4–SiO2 and H3PMo12O40; and also sodium stea-
rate was performed (Table 4). The summarized results in Table 4 illustrate that iod-
ine is the most effective catalyst for this transformation (entry 1).
Successful application of iodine as a catalyst for the one-pot synthesis of b-
phosphonomalonates via P-C bond formation encouraged us to study the applica-
bility of this method for the synthesis of 4-substituted 2-amino-4H-chromenes with
phosphonic acid diethyl ester by coupling reaction of salicylaldehyde, malononitrile=
ethylcyanoacetate, and triethyl phosphite (Scheme 4, Table 5).
Table 3. One-pot synthesis of b-phosphonomalonates from the reaction of different in situ–generated
Michael acceptors and trialkyl phosphites
Entry[ref]
R
X
Y
Product
Time (h)
Yielda (%)
1
Et
CN
CN
CN
CN
4
2
24
2
90
81
85
0
2[12]
3[13]
4
Me
iso-Pr
Et
16
17
—
—
—
—
—
CN
CN
CN
CO2Et
CO2Et
NO2
24
24
24
24
24
5
Et
Et
CO2Et
H
COMe
0
6
0
7
Et
Et
CO2Et
0
8
0
aIsolated yield. 4-Chlorobenzaldehyde (1 mmol), active methylene group (1 mmol), trialkyl phosphite
(1 mmol), catalyst (10 mol %), 50 ꢀC, solvent-free conditions. All the products were characterized by spec-
troscopic methods and compared with the authentic spectra.

SYNTHESIS OF b-PHOSPHONOMALONATES
3253
Table 4. Comparison of the catalytic efficiency of iodine with various catalysts
Entry
Catalyst
Time (h)
Yielda (%)
1
2
Iodine
CuO
2
85
37
46
45
54
41
46
47
48
45
24
24
24
24
24
24
24
24
24
3
Sb2O3
SnO2
4
5
HgO
MgO
CaO
6
7
8
HClO4–SiO2
H3PMo12O40
Sodium stearate
9
10
aIsolated yield. Conditions: catalyst (10 mol%), benzaldehyde (1 mmol), malononitrile (1 mmol), triethyl
phosphite, 50 ꢀC, solvent free.
Scheme 4. Synthesis of 4-substituted 2-amino-4H-chromenes with phosphonic acid diethyl esters catalyzed
by iodine.
As shown in Table 5, coupling reaction of substituted salicylaldehydes bearing
electron-withdrawing and electron-releasing groups with malononitrile and triethyl
phosphite proceeded well to give the corresponding products in good to excellent
yields (entries 1–4). The reaction of 3-methoxysalicylaldehyde and 3-ethoxysalicylal-
dehyde with ethylcyanoacetate and triethyl phosphite produced the desired products
in 94 and 80% yields, respectively (entries 5 and 6).
It is worth mentioning that 4-substituted 2-amino-4H-chromenes were intro-
duced as analogs of tumor antagonist HA 14-1 (Scheme 5).[16] HA 14-1 is a new class
of small molecules that exhibits binding activity for the surface pocket of the
Table 5. Synthesis of 4-substituted 2-amino-4H-chromene with phosphonic acid diethyl ester in the
presence of iodine
Entry[ref]
Aldehyde
Product
X
Time (h)
Yielda (%)
1[14]
2[15]
3[14b]
4
5[14b]
6
5-Bromosalicylaldehyde
5-Chlorosalicylaldehyde
3-Methoxysalicylaldehyde
3-Ethoxysalicylaldehyde
3-Methoxysalicylaldehyde
3-Ethoxysalicylaldehyde
18
19
20
21
22
23
CN
CN
4
3.5
1
79
81
93
82
94
80
CN
CN
1
CO2Et
CO2Et
2
2
aIsolated yield. Conditions: catalyst (10 mol%), salicylaldehyde (1 mmol), active methylene group
(1 mmol), triethyl phosphite, 50 ꢀC, solvent free.

3254
S. SOBHANI AND R. JAHANSHAHI
Scheme 5. Tumor agonist HA 14-1.
cancer-implicated Bcl-2 protein and induces apoptosis or programmed cell death in
follicular lymphoma B cells and leukemia HL-60 cells.[16]
EXPRIMENTAL
Typical Procedure for the Synthesis of [1-(4-Chlorophenyl)-
2,2-dicyanoethyl]phosphonic Acid Diethyl Ester (4)
Iodine (0.005 g, 10 mol%) was added to a mixture of 4-chlorobenzaldehyde
(0.141 g, 1 mmol), malononitrile (0.066 g, 1 mmol), and triethyl phosphite (0.166 g,
1 mmol). The reaction mixture was stirred at 50 ꢀC for 2 h under solvent-free
conditions. EtOH (10 mL) and Na2S2O3 (ꢁ0.3 g, in portion) were added to the
cooled reaction mixture. The resulting mixture was stirred for an additional
10 min and filtered. The filtrated cake was washed with EtOH (10 mL), and the sol-
vent was evaporated under reduced pressure to give the crude product. The crude
product was purified by chromatography eluted with n-hexane=EtOAc (1=1) and
gave product 4 (0.294 g, 90%) as a yellow solid.
Data
Mp 98 ꢀC; Rf ¼ 0.53; 1H NMR (250 MHz, CDCl3): d 1.16 (t, 3 H,
3
3
3JHH ¼ 7.0 Hz), 1.33 (t, 3 H, JHH ¼ 7.0 Hz), 3.62 (dd, 1 H, JHH ¼ 7.5 Hz,
2JHP ¼ 21.5 Hz), 3.82–4.19 (m, 4 H), 4.55 (t, 1 H, JHH ¼ 7.7 Hz), 7.42 (s, 4 H) ppm.
3
CONCLUSION
In conclusion, we have introduced a one-pot method for the successful synthesis
of b-phosphonomalonates via P-C bond formation through tandem Knoevenagel–
phospha–Michael reaction catalyzed by iodine as a new, inexpensive, nonmetallic,
and commercially available catalyst. A variety of b-phosphonomalonates were synthe-
sized by this simple method in good to excellent yields from the reaction of aldehydes
(aromatic, heteroaromatic, and aliphatic), malononitrile, and trialkyl phosphites.
Using this method, several 4-substituted 2-amino-4H-chromenes with phosphonic
acid diethyl ester were also synthesized by coupling reaction of salicylaldehyde,
malononitrile=ethylcyanoacetate, and triethyl phosphite in good to excellent yields.
SUPPORTING INFORMATION
Full experimental details, spectral data of the products, and 1H NMR and 13
C
NMR spectra of new compounds can be found via the Supplementary Content
section of this article’s Web page.

SYNTHESIS OF b-PHOSPHONOMALONATES
3255
ACKNOWLEDGMENT
We are thankful for all the support we received from the University of Birjand
Research Council.
REFERENCES
1. (a) Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. Renin inhibitors: Synthesis
of transition-state analogue inhibitors containing phosphorus acid derivatives at the sciss-
ile bond. J. Med. Chem. 1989, 32, 1652–1661; (b) Patel, D. V.; Rielly-Gauvin, K.; Ryono,
D. E. Preparation of peptidic a-hydroxy phosphonates, a new class of transition state ana-
log renin inhibitors. Tetrahedron Lett. 1990, 31, 5587–5590; (c) Stowasser, B.; Budt, K. H.;
Li, J. Q.; Peyman, A.; Ruppert, D. New hybrid transition state analog inhibitors of HIV
protease with peripheric C2-symmetry. Tetrahedron Lett. 1992, 33, 6625–6628.
2. Kafarski, P.; Lejczak, B. Biological activity of aminophosphonic acids. Phosphorus, Sulfur
Silicon Relat. Elem. 1991, 63, 193–215.
3. (a) Baylis, E. K.; Campbell, C. D.; Dingwall, J. G. 1-Aminoalkylphosphonous acids, part 1:
Isosteres of the protein amino acids. J. Chem. Soc, Perkin Trans. 1 1984, 2845–2853; (b)
Atherton, F. R.; Hassall, C. H.; Lambert, R. W. Synthesis and structure–activity relation-
ships of antibacterial phosphonopeptides incorporating (1-aminoethyl)phosphonic acid
and (aminomethyl)phosphonic acid. J. Med. Chem. 1986, 29, 29–40.
4. (a) Pudovik, A. N.; Konovalova, I. V. Addition reactions of esters of phosphorus(III)
acids with unsaturated systems. Synthesis 1979, 81–96; (b) Enders, D.; Saint-Dizier,
A.; Lannou, M. I.; Lenzen, A. The phospha-Michael addition in organic synthesis.
Eur. J. Org. Chem. 2006, 29–49; (c) Miller, R. C.; Bradley, J. S.; Hamilton, L. A. Dis-
ubstituted phosphine oxides, III: Addition to a,b-unsaturated nitriles and carbonyl com-
pounds. J. Am. Chem. Soc. 1956, 78, 5299–5303; (d) Bodalski, R.; Pietrusiewicz, K. A
new route to the phospholane ring system. Tetrahedron Lett. 1972, 13, 4209–4212; (e)
Simoni, D.; Invidiata, F. P.; Manferdini, M.; Lampronti, I.; Rondanin, R.; Roberti,
M.; Pollini, G. P. Tetramethylguanidine (TMG)–catalyzed addition of dialkyl phosphites
to a,b-unsaturated carbonyl compounds, alkenenitriles, aldehydes, ketones, and imines.
Tetrahedron Lett. 1998, 39, 7615–7618; (f) Hosseini-Sarvari, M.; Etemad, S. Nanosized
zinc oxide as a catalyst for the rapid and green synthesis of b-phosphono malonates.
Tetrahedron 2008, 64, 5519–5523; (g) Green, K. Trimethylaluminum-promoted conjugate
additions of dimethylphosphite to a,b-unsaturated esters and ketones. Tetrahedron Lett.
1989, 30, 4807–4810; (h) Hindersinn, R. R.; Ludington, R. S. The reaction of trialkyl
phosphites with maleate esters. J. Org. Chem. 1965, 30, 4020–4025; (i) Shulyupin, M.
O.; Kazankova, M. A.; Beletskaya, I. P. Catalytic hydrophosphination of styrenes.
Org. Lett. 2002, 4, 761–763; (j) Xu, Q.; Han, L.-B. Palladium-catalyzed asymmetric
hydrophosphorylation of norbornenes. Org. Lett. 2006, 8, 2099–2101; (k) Semenzin,
D.; Etemad-Moghadam, G.; Albouy, D.; Diallo, O.; Koenig, M. Dual radical=polar
Pudovik reaction: Application field of new activation methods. J. Org. Chem. 1997,
62, 2414–2422; (l) Han, L.-B.; Zhao, C.-Q. Stereospecific addition of H-P bond to
alkenes: A simple method for the preparation of (RP)-phenylphosphinates. J. Org. Chem.
2005, 70, 10121–10123; (m) Stockland, Jr., R. A.; Taylor, R. I.; Thompson, L. E.; Patel,
P. B. Microwave-assisted regioselective addition of P(O)-H bonds to alkenes without
added solvent or catalyst. Org. Lett. 2005, 7, 851–853; (n) Mahran, M. R.; Abdou,
W. M.; Abd El-Rahman, N. M.; Khidre, M. D. Organophosphorus chemistry 23 [1],
the reaction of a,b-unsaturated nitriles with alkyl phosphites and phosphorus ylides.
Heteroatom Chem. 1992, 3, 93–99.

3256
S. SOBHANI AND R. JAHANSHAHI
5. Jiang, Z.; Zhang, Y.; Ye, W.; Tan, C.-H. P–C bond formation via direct and
three-component conjugate addition catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene
(TBD). Tetrahedron Lett. 2007, 48, 51–54.
6. Kolla, S. R.; Lee, Y. R. Efficient one-pot synthesis of b-phosphono malonates and
2-amino-4H-chromen-4-ylphosphonate derivatives by ethylenediamine diacetate-
catalyzed three-component reactions. Tetrahedron 2012, 68, 226–237.
7. (a) Ramachandran, G.; Karthikeyan, N. S.; Giridharan, P.; Sathiyanarayanan, K. I.
Efficient iodine-catalyzed three-component domino reaction for the synthesis of
1-((phenylthio)(phenyl)methyl)pyrrolidin-2-one derivatives possessing anticancer activi-
ties. Org. Biomol. Chem. 2012, 10, 5343–5346; (b) Gao, S.; Tzeng, T.; Sastry, M. N. V.;
Chu, C.-M.; Liu, J.-T.; Lin, C.; Yao, C.-F. Iodine-catalyzed conjugate addition of mer-
captans to a,b-unsaturated carboxylic acids under solvent-free condition. Tetrahedron
Lett. 2006, 47, 1889–1893; (c) Banik, B. K.; Fernandez, M.; Alvarez, C. Iodine-catalyzed
highly efficient Michael reaction of indoles under solvent-free condition. Tetrahedron Lett.
2005, 46, 2479–2482; (d) Kidwai, M.; Bansal, V.; Mothsra, P.; Saxena, S.; Somvanshi, R.
K.; Dey, S.; Singh, T. P. Molecular iodine: A versatile catalyst for the synthesis of
bis(4-hydroxycoumarin) methanes in water. J. Mol. Catal. A: Chem. 2007, 268, 76–81;
(e) Ge, W.; Wei, Y. Iodine-catalyzed oxidative system for 3-sulfenylation of indoles with
disulfides using DMSO as oxidant under ambient conditions in dimethyl carbonate. Green
Chem. 2012, 14, 2066–2070.
8. (a) Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Metal triflate–catalyzed one-pot synthesis
of a-aminophosphonates from carbonyl compounds in the absence of solvent. Synthesis
2004, 2692–2696; (b) Sobhani, S.; Safaei, E.; Asadi, M.; Jalili, F.; Tashrifi, Z. Efficient syn-
thesis of secondary and primary dialkyl a-aminophosphonates catalyzed by
tetramethyl-tetra-3,4-pyridinoporphyrazinato copper(II) methyl sulfate under solvent-free
conditions. J. Porphyrins Phthalocyanines 2008, 12, 849–856; (c) Sobhani, S.; Safaei, E.;
Asadi, M.; Jalili, F. An ecofriendly procedure for the efficient synthesis of dialkyl a-ami-
nophosphonates in aqueous media. J. Organomet. Chem. 2008, 693, 3313–3317; (d)
Sobhani, S.; Tashrifi, Z. Al(OTf)3 as an efficient catalyst for one-pot synthesis of primary
diethyl 1-aminophosphonates under solvent-free conditions. Synth. Commun. 2009, 39,
120–131; (e) Sobhani, S.; Tashrifi, Z. One-pot synthesis of primary 1-aminophosphonates:
Coupling reaction of carbonyl compounds, hexamethyldisilazane, and diethyl phosphite
catalyzed by Al(OTf)3. Heteroatom Chem. 2009, 109–115; (f) Sobhani, S.; Vafaee, A.
Micellar solution of sodium dodecyl sulfate (SDS) catalyzes Kabacknik–Fields reaction
in aqueous media. Synthesis 2009, 1909–1915; (g) Sobhani, S.; Vafaee, A. Efficient one-pot
synthesis of b-hydroxyphosphonates: Regioselective nucleophilic ring-opening reaction of
epoxides with triethyl phosphite catalyzed by Al(OTf)3. Tetrahedron 2009, 65, 7691–7695;
(h) Sobhani, S.; Rezazadeh, S. HClO4-SiO2 as a novel and recyclable catalyst for the
phospha-Michael addition of phosphorous nucleophiles to a,b-unsaturated malonates.
Synlett 2010, 1485–1488; (i) Sobhani, S.; Pakdin Parizi, Z.; Rezazadeh, S.
Phospha-Michael addition of phosphorus nucleophiles to a,b-unsaturated malonates
using 3-aminopropylated silica gel as an efficient and recyclable catalyst. J. Organomet.
Chem. 2011, 696, 813–817; (j) Sobhani, S.; Rezazadeh, S. Phosphomolybdic acid: An
efficient and reusable catalyst for the synthesis of b-phosphono malonates. J. Iran. Chem.
Soc. 2011, 8, 198–203; (k) Sobhani, S.; Pakdin Parizi, Z. An eco-friendly procedure for
one-pot synthesis of b-phosphonomalonates: Micellar solution of sodium stearate cata-
lyzes tandem Knoevenagel–phospha–Michael reaction of aldehydes, malonitrile, and
phosphites in aqueous media. Tetrahedron 2011, 67, 3540–3545; (l) Sobhani, S.; Pakdin
Parizi, Z.; Razavi, N. Nano n-propylsulfonated c-Fe2O3 as magnetically recyclable hetero-
geneous catalyst for the efficient synthesis of b-phosphonomalonates. Appl. Catal. A: Gen.
2011, 409–410, 162–166; (m) Sobhani, S.; Honarmand, M. 5-Hydroxypentylammonium

SYNTHESIS OF b-PHOSPHONOMALONATES
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acetate as a reusable ionic liquid catalyzes tandem Knoevenagel–phospha–Michael reac-
tion of aldehydes, malononitrile, and phosphites. J. Iran. Chem. Soc. 2012, 9, 661–669.
9. Sobhani, S.; Vafaee, A. Molecular iodine: An efficient catalyst for the one-pot synthesis of
primary 1-aminophosphonates. J. Iran. Chem. Soc. 2010, 7, 227–236.
10. Fahmy, A. A.; Ismail, N. A.; Hafez, T. S. Reaction of alkyl phosphites on some deriva-
tives of malononitriles. Phosphorus, Sulfur Silicon Relat. Elem. 1992, 66, 201–205.
11. Abdou, W. M.; Khidre, M. D.; Mahran, M. R. Organophosphorus chemistry, 16: The
reaction of furfurylidenemalonitrile with alkyl phosphites. J. Prakt. Chem. 1990, 332,
1029–1034.
12. Lilia Ben, G.; Hedi, Z. Action des hydrazines et de l’hydroxylamine sur quelques phos-
phonates b,b-bifonctionnalises: Synthese de phosphonoaminopyrazoles et isoxazoles.
Phosphorus, Sulfur Silicon Relat. Elem. 2000, 157, 153–164.
13. Rymareva, T. G.; Sandakov, V. B.; Khaskin, B. A.; Promonenkov, V. K.; Koroleva, T. I.
Synthesis of sodium derivatives of phosphorylated 1,1-dicyanoethanes. Zh. Obshch. Khim.
1982, 52, 220–221.
14. (a) Jayashree, P.; Shanthi, G.; Perumal, P. T. Indium trichloride–catalyzed one-pot syn-
thesis of new (2-amino-3-cyano-4H-chromen-4-yl) phosphonic acid diethyl ester. Synlett
2009, 6, 917–920; (b) Narayana Murthy, S.; Madhav, B.; Prakash Reddy, V.; Nageswar,
Y. V. D. One-pot synthesis of 2-amino-4H-chromen-4-yl phosphonate derivatives using
b-cyclodextrin as reusable catalyst in water. Tetrahedron Lett. 2010, 51, 3649–3653.
15. Kulkarni, M. A.; Pandurangi, V. R.; Desai, U. V.; Wadgaonkar, P. P. A practical and
highly efficient protocol for multicomponent synthesis of b-phosphonomalononitriles
and 2-amino-4H-chromen-4-yl phosphonates using diethylamine as a novel organocata-
lyst. C. R. Chim. 2012, 15, 745–752.
16. (a) Skommer, J.; Wlodkowic, D.; Matto, M.; Eray, M. HA14–1, a small molecule Bcl-2
antagonist, induces apoptosis and modulates action of selected anticancer drugs in follicu-
lar lymphoma B cells. J. Pelkonen, Leukemia Res. 2006, 30, 322–331; (b) Wang, J. L.; Liu,
D.; Zhang, Z.; Shan, S.; Han, X.; Srinvasula, S. M.; Croce, C. M.; Alnemeri, E. S.; Huang,
Z. Structure-based discovery of an organic compound that binds Bcl-2 protein and
induces apoptosis of tumor cells. Proc. Natl. Acad. Sci. USA 2000, 97, 7124–7129.