A practical and highly efficient protocol for multicomponent synthesis of β-phosphonomalononitriles and 2-amino-4H-chromen-4-yl phosphonates using diethylamine as a novel organocatalyst

Article abstract of DOI:10.1016/j.crci.2012.07.001

Diethylamine has been demonstrated for the first time to be a highly efficient organocatalyst in the solvent-free synthesis of β- phosphonomalononitriles by a three component condensation of aldehyde, malononitrile and dialkyl phosphite at ambient temperature. The applicability of the same catalyst in the synthesis of diethyl (2-amino-3-cyano-chromene-4-yl) phosphonic acid esters has also been described.

Full text of DOI:10.1016/j.crci.2012.07.001

C. R. Chimie 15 (2012) 745–752
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Preliminary communication/Communication
A practical and highly efficient protocol for multicomponent synthesis
of -phosphonomalononitriles and 2-amino-4H-chromen-4-yl
b
phosphonates using diethylamine as a novel organocatalyst
b
M.A. Kulkarni a, V.R. Pandurangi a, U.V. Desai a, , P.P. Wadgaonkar
*
a Organic Chemistry Division, Department of Chemistry, Shivaji University, Kolhapur 416,004, India
b Polymer Science and Engineering Division, National Chemical Laboratory, Pune 411,008, India
A R T I C L E I N F O
A B S T R A C T
Article history:
Diethylamine has been demonstrated for the first time to be
a highly efficient
Received 8 February 2012
Accepted after revision 2 July 2012
Available online 13 August 2012
organocatalyst in the solvent-free synthesis of
b-phosphonomalononitriles by a three
component condensation of aldehyde, malononitrile and dialkyl phosphite at ambient
temperature. The applicability of the same catalyst in the synthesis of diethyl (2-amino-3-
cyano-chromene-4-yl) phosphonic acid esters has also been described.
Keywords:
´
ß 2012 Published by Elsevier Masson SAS on behalf of Academie des sciences.
b-phosphonomalononitriles
Phospha-Michael reaction
Multicomponent reactions
Diethylamine
Organocatalyst
2-amino-4H-chromenes
1. Introduction
approaches to address this challenge rely in the selection
of an appropriate reaction path as well as catalyst.
An art to develop operationally simple and environ-
mentally benign routes for organic compounds having
high synthetic as well as biological potential is one of the
fundamental objectives in synthetic organic chemistry
[1]. In this context, the possibility of performing one-pot
condensation of three or more components, multicompo-
nent reactions (MCRs), is of relevance both from an
economical as well as ecological point of view [2].
Although the main attraction of multicomponent reac-
tions is their ability to construct two or more C-C or
C-heteroatom bonds in single step, a typical challenge in
performing them is to obtain only the desired product
when competitive two component reactions between the
selected substrates are equally probable. Two main
Phosphonates are important intermediates in organic
synthesis and their utility in Wittig and related reactions is
well documented [3]. Currently they have also been the
focus of intensive studies due to their usefulness as
enzyme inhibitors [4], metabolic probes [5], peptide
mimetics [6], antibiotics, pharmacologic agents [7], etc.
Many natural products containing C–P bond are also
known to exhibit important biological activities [8]. Owing
to such a wide range of applications, development of
efficient protocols for the synthesis of phosphonates,
phosphonic acids and related compounds via C–P bond
formation is enjoying growing interest. It is worth
mentioning that, apart from the Kabaschnik-Field, Michae-
lis-Beker, and Michaelis-Arbuzov reaction [9], addition of
phosphite nucleophile across carbon-carbon double bond
(phospha-Michael reaction) is an ever green and widely
used method in C–P bond formation [10,11]. The reaction
is usually catalyzed by alkaline earth metal oxides [12],
transition metal catalysts [13], tetramethylguanidine [14],
Lewis/Bronsted acids [15], MWs [16], etc. In the recent
* Corresponding author.
E-mail addresses: uvdchem2011@gmail.com,
uprabhu_desai@rediffmail.com (U.V. Desai).
1631-0748/$ – see front matter ß 2012 Published by Elsevier Masson SAS on behalf of Acade´mie des sciences.
http://dx.doi.org/10.1016/j.crci.2012.07.001

746
M.A. Kulkarni et al. / C. R. Chimie 15 (2012) 745–752
(OEt)2
O
P
CHO
O
P
K3PO4 / Et2NH
Neat, RT
OH
a)
b)
+
H
(OEt)2
MeO
MeO
MeO
K3PO4 (10 mol %) : 3 = 100 %
Et2NH (100 mol %); 3 = 100 %
1
1
3
2
(OEt)2
O
P
CHO
CN
CN
CN
CN
K3PO4 / Et2NH
O
P
3
+
+
+
+
CN
CN
H
(OEt)2
MeO
Neat, RT
MeO
6
5
4
K3PO4 ; 3 : 5 : 6 = 0 ; 50 : 50 %
Et2NH ; 3 : 5 : 6 = 0 : 0 : 100 %
O
P
CHO
Et2NH,
H
(OEt)2
CN
CN
6
c)
5
5
+
+
Neat, RT
MeO
5 : 6 = 50 : 50 %
1
4
Scheme 1. Screening of reaction path/catalyst for one-pot synthesis of
b-phosphonomalononitrile.
past, the phospha-Michael reaction has been explored in
the synthesis of -phosphonomalononitriles using HClO4.-
condensation product, 5 and the desired
b
-phosphono-
b
malononitrile, 6, in nearly 1:1 proportion (1H-NMR). Most
SiO2 [17a], 3-aminopropylated silica gel [17b], nanoflake-
ZnO [17c], sodium stearate [17d], etc. as catalysts. Many of
these two component protocols essentially involve addi-
tion of phosphite nucleophile to benzylidine malononi-
strikingly, formation of a-hydroxy phosphonate, 3, was not
noticed (Scheme 1b). In short, although potassium
phosphate has been demonstrated by us as a highly
efficient catalyst to effect two component condensations
between an aldehyde and diethyl phosphite [20b] as well
as between an aldehyde and active methylene compounds
[19f], during a three component condensation using these
substrates, the reaction exclusively followed the tandem
Knoevenagel-phospha-Michael pathway. This break-
through result directed us to test the feasibility in using
trile; however, reports on one-pot synthesis of
b-
phosphonomalononitriles are scanty [18]. Our interest in
this class of compounds stems from the ongoing studies in
our laboratory on the development of new synthetic
methodologies [19] including a recent report on expedi-
tious synthesis of
a-hydroxy phosphonates using potassi-
um phosphate as well as diethylamine as catalyst [20]
(Scheme 1a). Based upon these results, we further expand
other base catalysts in one-pot synthesis of b-phospho-
nomalononitriles. Accordingly, various homogeneous and
heterogeneous base catalysts were screened for this three
component condensation reaction (Table 1). It was noticed
that, under solvent-free condition, compared to inorganic
salts (entry 2, 3, 4 & 5, Table 1), organic bases such as
pyrrolidine, piperidine and diethylamine (entry 11, 12, 13,
Table 1), with very close pKa values, were equally efficient
this chemistry towards the synthesis of
b-phosphonoma-
lononitriles using diethylamine as a novel organocatalyst.
2. Results and discussion
For one-pot synthesis of
b-phosphonomalononitriles,
one of the cleaner routes involves a base catalyzed,
multicomponent condensation between an aldehyde,
malononitrile and di/tri alkyl phosphite. On the other
hand, a typical challenge in execution of this route relies in
the choice of a base catalyst which would furnish the
to furnish the desired b-phosphonomalononitrile in
excellent yield. On the other hand, with the choice of
heterogeneous catalysts like PVP, DBU, DMAP as well as
DABCO, the reactions furnished a mixture of
phosphonate and -phosphonomalononitrile in different
proportions. From the view point of operational simplicity,
another cleaner route for the synthesis of -phosphono-
a-hydroxy
b
targeted
b-phosphonomalononitrile, 6, in excellent yields
with total avoidance of the formation of
a
-hydroxy
b
phosphonate, 3, via the competitive Pudovik Reaction
[21]. Thus, we planned to develop a base catalyzed one-pot
malononitriles involves the sequential, one-pot, Knoeve-
nagel-phospha-Michael addition reaction (Scheme 1c).
During exploration of this route, Knoevenagel condensa-
tion between anisaldehyde and malononitrile was initially
effected using diethylamine as catalyst. To the resultant
product, 5, diethyl phosphite (1 eqv) was added and
stirring was continued over night. The resultant crude
product was identified (1H- NMR) to be a mixture of
protocol for the synthesis of
b-phosphonomalononitriles.
Initial exploratory reaction was carried out between
anisaldehyde, malononitrile and diethyl phosphite using
potassium phosphate as a catalyst (10 mol %). The crude
product which resulted after stirring the reaction mixture
over night was identified to be a mixture of Knoevenagel

M.A. Kulkarni et al. / C. R. Chimie 15 (2012) 745–752
747
Table 1
Knoevenagel condensation product, 5 and the desired
phospha-Michael addition product, 6, in nearly 1:1
proportion. Finally, a control experiment was carried out
using the same substrate combination. In absence of a
catalyst, the reaction furnished a mixture of products
(Entry 1, Table 1). Based upon the results summarized in
Table 1 and on the basis of parameters of commercial
availability, low toxicity, cost, ease in handling as well as
its easy removal from the reaction mixture, diethylamine
was recognized to be the best suited organocatalyst in the
one-pot synthesis of B-phosphonomalononitriles. A careful
literature survey very interestingly revealed that there are
no reports on the use of diethylamine in any multicompo-
nent reaction. Thus, it was then planned to explore the
generality of the reaction conditions towards the synthesis
Effect of catalyst in one-pot synthesis of
b-phosphonomalononitrile, 6e.
No.
Catalyst
Time
Yield (%)a
(mol %/mgm)
(h)
3
5
6
1
–
24
40
–
40
50
50
–
20
50
50
70
60
–
2
K3PO4 (10)
12
3
K3PO4 (20)
12
–
4
Borax (200 mg)
MgO (200)
Amberlite (OHÀ, 200 mg)
PVP (100 mg)
DBU (10)
12
20
20
20
20
80
80
40
–
5
10
20
80
70
20
20
20
–
6
16
7
16
–
8
30b
30b
2
–
9
DABCO (10)
DMAPc
–
10
11
12
13
40
90
90
95
Pyrrolidine (10)
Piperidine (10)
Diethylamine (10)
30b
30b
15b
–
–
–
–
of various
b-phosphonomalononitriles. Initially, the reac-
Reaction conditions: anisaldehyde, malononitrile, diethyl phosphite
(2 mmol, each), catalyst, Neat, RT.
tions were performed between malononitrile, diethyl
phosphite and various aromatic aldehydes bearing elec-
tron withdrawing (6h, Table 2) as well as electron donating
groups (6e, g, Table 2) and having obtained the satisfactory
a
Yields based upon TLC comparison with authentic samples.
b
Time in minutes.
c
Dimethylamino pyridine.
Table 2
Diethyl amine catalyzed one-pot synthesis of
b-phosphonomalononitriles.
Entry
a
Product (6)
Time (min)
10
Yield (%)
96
Ref.
[18c]
O
P
(OEt)2
CN
CN
O
(R)2
P
CN
CN
b
c
R = CH3
R = C2H5
10
15
15
94
90
93
–
[17d]
–
d
R = HC(CH3)2
e
15
10
10
95
95
93
[18a,18c]
[17d,18c]
–
O
(OEt)2
CN
P
CN
MeO
O
f
(OEt)2
P
CN
CN
Cl
g
O
(OEt)2
CN
P
MeO
MeO
CN
h
20
15
94
96
–
–
O
(OEt)2
CN
P
O2N
CN
i
O
(OEt)2
CN
P
CN

748
M.A. Kulkarni et al. / C. R. Chimie 15 (2012) 745–752
Table 2 (Continued )
Entry
Product (6)
Time (min)
15
Yield (%)
90
Ref.
j
[17f]
O
(OEt)2
P
P
CN
CN
O
O
k
20
15
95
93
[17b]
[17e]
O
O
O
(OEt)2
CN
CN
HO
NC
l
(OEt)2
CN
P
P
CN
m
n
30
20
30
84a
–
(OEt)2
CN
CN
90
[17a]
[17a,b]
O
O
(OEt)2
CN
P
P
S
CN
o
87
(OEt)2
CN
CN
p
q
3b
30
[17a]
[17b]
O
O
(OEt)2
Y
P
P
X
15
95c
(OEt)2
CN
COOEt
Reaction conditions: aldehyde, malononitrile/ethyl cyanoacetate and diethyl phosphite (2 mmol, each), diethyl amine (10 mol %), rt.
a
Mixture of products.
b
Time in hours.
dr = 60:40 (1H NMR).
c
results, the scope of the protocol was extended towards
heteroaromatic (6n, Table 2) as well as non-aromatic
aldehyde (6o, Table 2). Except aliphatic aldehyde, (6p,
furnish diastereoisomeric mixture of desired phosphono-
cyanomalonate (6q, Table 2, dr = 60:40, 1H NMR) while the
reactions using diethyl malonate or phenylsulfonyl aceto-
nitrile yielded a mixture of products.
Table 2), in all cases, respective b-phosphonomalononitrile
was obtained in a short time, in excellent yield as well as
purity. (Table 2) We then investigated the possibility of
replacing diethyl phosphite with dimethyl and di-iso-
propyl phosphite. (Table 2, entry b, d). In all the cases the
reactions were equally smooth and furnished correspond-
As regards the one-pot synthesis of b-phosphonoma-
lononitriles, an interesting observation is noteworthy. The
catalyst, diethylamine, which was found to be highly
efficient to furnish
b-phosphonomalononitrile following
the multicomponent pathway (Scheme 1b), was unable to
drive sequential, Knoevenagel-phospha-Michael reaction
to completion (Scheme 1c). At this stage of our work, we do
not have any concrete answer to explain this anomaly.
However, with reference to our recent report on catalyst as
well as solvent-free protocol for Michael addition of
anilines to enones [22] and our current experiences in the
ing
b-phosphonomalononitrile in excellent yield. In an
attempt to broaden the scope of this protocol, studies were
also performed using ethyl cyanoacetate, diethyl malonate
and phenylsulfonyl acetonitrile as other active methylene
components. Interestingly, with the choice of ethyl
cyanoacetate alone, the reaction proceeded smoothly to

M.A. Kulkarni et al. / C. R. Chimie 15 (2012) 745–752
749
(OEt)2
CN
NC
COOEt
COOEt
O
synthesis of
b-phosphonomalononitriles, we believe that
P
this anomaly is possibly concerned with the difference in
the amount of heat liberated in following the two different
pathways. It could be shown very easily that, under
solvent-free condition, the heat released upon addition of
diethylamine to a mixture of aldehyde, malononitrile and
diethyl phosphite is much larger than that released upon
addition of diethyl phosphite to a stirred mixture of
Knoevenagel condensation product and diethylamine. In
short, the heat released during this MCC reaction might be
sufficient enough to drive this tandem Knoevenagel-
phospha-Michael reaction to completion.
Br
O
NH2
O
NH2
B
A
COOEt
NC
CN
COOEt
NH2
CN
O
O
NH2
C
D
Following this initial success in the development of a
R1
EtOOC
COOEt
COOEt
R
NO2
one-pot protocol for the synthesis of
b-phosphonomalo-
Br
nonitriles, it was planned to explore the applicability of the
developed protocol towards designing of molecular frame
work in a few biologically active compounds. In this
context, our attention became focused on the synthesis of
2-amino-4H-chromenes (Fig. 1).
X
O
NH2
O
NH2
E
F
X = CN, COOEt R = H, R1 = H, Me, Et, etc.
;
The chromene moiety often appears as an important
structural motif in many natural products while chromene
pharmacophore can serve as a useful building block in the
generation of a variety of natural products with important
biological activities [23]. Among different types of
chromenes, 2-amino-4H-chromene derivatives constitute
an important class of heterocycles customarily used in
cosmetics, pigments and biodegradable agrochemicals
[24]. They are also known to exhibit important biological
activities such as antimicrobial, antiviral, antitumor,
antihypertensive anti-ischemic behavior, etc. [25–27].
With the rapid progress both in chemistry as well as
biology of 2-amino-4H-chromenes, development of a
protocol meeting to the demands of an ‘‘ideal synthesis’’
[28] is highly desirable. It is worth mentioning that,
amongst various 2-amino-4H-chromene derivatives, syn-
thesis of (2-amino-3-cyano-4H-chromen-4-yl) phospho-
nic acid diethyl ester derivatives, 11, has been reported
Fig. 1. Structures of a few biologically active 2-amino-4H-chromene
derivatives.
[18c] as catalysts. In light of the developed protocol for the
expeditious synthesis of
b-phosphonomalononitriles, we
envisaged that, diethyl amine catalyzed three component
condensation between ortho-hydroxy benzaldehyde, mal-
ononitrile and diethyl phosphite would easily furnish
diethyl (2-amino-3-cyano-4H-chromen-4-yl) phospho-
nate, 11a, following one of the paths depicted in Scheme 2.
In a template reaction, salicylaldehyde, malononitrile
and diethyl phosphite were stirred together at ambient
temperature in presence of diethylamine (10 mol %) as
catalyst. It was truly gratifying to notice that the resultant
product in excellent yield was the desired chromene
derivative, 11a (Table 3, Scheme 3).
This initial success prompted us to explore the potential
of this protocol in the synthesis of various 2-amino-4H-
chromene derivatives. Accordingly, the reactions were
earlier using InCl3 [29a], potassium phosphate [29b],
b-
cyclodextrin [29c] as well as ethylenediaminediacetate
O
(OEt)2
X
O
(OEt)2
X
(OEt)2
O
P
P
P
H
X
+
X
Et2NH
H
-
Path A)
CN
OH
HP(O) (OEt)2
N
OH
N
NH
O
O
-
Et2NH
-
Nu
(OEt)2
X
O
P
X
X
X
+
H
HP(O) (OEt)2
(NuH)
N
Path B)
-
O
N
O
O
NH
N
NH2
-
-
9 : X = CN
10 : X = COOEt / CN
11, Nu = P(O) (OEt)2 ; X = CN
-
12 ; Nu = P(O) (OEt)2 ; X = COOEt
Scheme 2. Plausible mechanism for the formation of (2-amino-3-cyano-4H-chromen-4-yl) phosphonic acid esters.

750
M.A. Kulkarni et al. / C. R. Chimie 15 (2012) 745–752
Table 3
performed between various substituted salicylaldehydes,
malononitrile and diethyl phosphite. The attempted
reactions under solvent-free conditions were slightly
exothermic and failed to furnish corresponding 2-ami-
no-4H-chromene derivatives in high yields as well as
purity. However, with the choice of ethanol as an
ecofriendly reaction medium, the reactions with all the
substituted salicylaldehydes proceeded smoothly (Table
3). To expand the scope of the developed protocol,
malononitrile component in above reaction was then
replaced by ethyl cyanoacetate. However, the reaction
Diethyl amine catalyzed synthesis of (2-amino-3- cyanochromen-4-yl)
phosphonic acid diethyl esters, 11a-h.
O
(OEt)2
CN
O
P
CN
CN
O
P
H
Et2NH
RT
+
+
OH
(OEt)2
H
O
NH2
R
R
11
7
Entry
Product (11)
Time
(h)
Yield
(%)a
M.P (8 C)
(Rep)
product was identified to be
a mixture (TLC) and
modification of the reaction conditions as regards change
in the reaction temperature as well as solvent was not
found to be beneficial to obtain the desired phosphonate
ester, 12, (Scheme 2) as a sole product. Interestingly, when
the diethyl phosphite component in above reaction was
replaced with triethyl phosphite, the reaction did not go to
completion.
ref./Ods.
a
2
95
(140–142)
[29a]/
O
(OEt)2
CN
P
139–140
O
NH2
b
c
6
92
94
150–152
O
(OEt)2
P
3. Conclusion
Cl
Cl
CN
In conclusion, we have described for the first time, the
use of diethylamine as a highly efficient organocatalyst in a
one-pot, multicomponent synthesis of b-phosphonoma-
O
P
NH2
2.5
(172–174)
[29b]/
O
(OEt)2
CN
lononitriles at ambient temperature. Usability of the same
catalyst in synthesis of diethyl (2-amino-3-cyano-4H-
chromen-4-yl) phosphonic acid esters has also been
described. Easy commercial availability of non-toxic
catalyst at extremely low cost, ambient temperature,
excellent yields, operational simplicity, easy work-up
procedures have made this greener protocol a user friendly
alternative to the exiting ones.
In continuation of these studies, diethylamine cata-
lyzed synthesis of other chromene derivatives B-F (Fig. 1)
has also been accomplished and those results will be
reported separately.
172–174
O
P
NH2
Cl
d
2
95
93
(180–82)
[29a]/
O
O
(OEt)2
CN
180–182
Br
Br
O
P
NH2
e
2.5
(198–200)
[18c]/
(OEt)2
CN
194–197
4. Experimental
O
NH2
Dialkyl phosphites, aldehydes (Aldrich), potassium
phosphate (Lancaster), diethylamine and malononitrile
(SD Fine Chemicals, Mumbai) were used as received.
Melting points were recorded in open capillaries using
Kumar melting point apparatus. IR spectra were recorded
as KBr discs or as neat, using Perkin Elmer Spectrum-1 IR
spectrometer. 1H (300 MHz) and 13C (75.4 MHz) NMR
spectra were recorded as CDCl3 solutions using TMS as
internal standard on Bruker Avance II spectrometer. GCMS
spectra were recorded using Shimatzu-QP 2010 analyzer.
Br
f
2
2
95
90
(213–215)
[18c]/
O
(OEt)2
CN
P
O2N
216–218
O
NH2
g
(160–162)
[18c]/
O
(OEt)2
CN
P
161–164
O
NH2
4.1. Typical experimental procedure
4.1.1. Synthesis of
b-phosphonomalononitriles, 6a–o
h
2
92
(180–182)
[18c]/
O
P
(OEt)2
CN
To an equimolar and well stirred mixture of aldehyde,
diethyl phosphite and malononitrile (2 mmol, each) was
added diethyl amine (10 mol %) and stirring continued.
Upon completion of reaction, (tlc) water (10 mL) was
added and the reaction mixture was extracted using ethyl
acetate. The organic extract was washed with water, dried
over anhydrous sodium sulphate and solvent removed. The
178–182
MeO
O
NH2
a
Salicylaldehyde, malononitrile and diethyl phosphite (2 mmol, each)
ethanol (3 mL), diethylamine (10 mol %), rt.

M.A. Kulkarni et al. / C. R. Chimie 15 (2012) 745–752
751
(d, 3JCP = 3.8 Hz, CH3), 25.80 (CH), 44.23 (d, 1JCP = 144.7 Hz,
CH), 55.72, 55.90, 63.14 (d, JCP = 6.7 Hz, CH2), 64.24 (d,
2JCP = 6.7 Hz, CH2), 111.12 (d, 3JCP = 10.5 Hz, CN), 111.40 (d,
3JCP = 10.5 Hz, CN), 111.97, 112.04, 122.10, 122.15, 122.20,
149.46, 149.97, 149.99 ppm; GCMS: m/z = 352, 287, 259,
214, 177, 151, 138, 121.
O
(OEt)2
CN
O
P
2
CN
CN
O
P
H
Et2NH
RT
+
+
OH
(OEt)2
H
O
NH2
R
R
11
7
[1-(3-Nitrophenyl)-2,2-dicyanoethyl] phosphonic acid
diethyl ester, (6 h): IR (CHCl3): 2944, 2833, 2205, 1537,
Scheme 3. Diethylamine catalyzed synthesis of (2-amino-3-
cyanochromen-4-yl) phosphonic acid diethyl esters, 11.
1354, 1251, 1024 cmÀ1 1H NMR (300 MHz, CDCl3):
d = 1.26
;
(t, 3H, J = 7.2 Hz), 1.37 (t, 3H, J = 6.9 Hz), 3.71 (dd, 1H,
2JHP = 21.6 Hz, 3JHH = 7.5 Hz), 3.95–4.27 (m, 4H), 4.58 (t, 1H,
3JHP = 3JHH = 7.8 Hz), 7.69 (t, 1H, J = 7.8 Hz), 7.87 (dd, 1H,
resultant oil was chromatographed over silica-gel. Elution
with hexane-ethyl acetate (90:10) furnished the desired
phosphonomalononitrile in excellent yield.
b-
J = 7.5 and 0.9 Hz), 8.32–8.37 (m, 2H); 13C NMR (75.4 MHz,
3
CDCl3):
d
= 16.09 (d, JCP = 5.2 Hz, CH3), 16.18 (d,
1
4.1.2. Synthesis of (2-amino-3-cyano-chromene-4-yl)
phosphonic acid diethyl ester derivatives, 11a–g
3JCP = 6.0 Hz, CH3), 25.07 (CH), 43.45 (d, JCP = 143.1 Hz,
2
2
CH), 63.80 (d, JCP = 6.7 Hz, CH2), 64.35 (d, JCP = 6.7 Hz,
CH2), 111.20 (d, 3JCP = 9.8 Hz, CN), 111.30 (d, 3JCP = 11.3 Hz,
CN), 124.21, 124.58, 124.67, 130.33, 133.09, 133.17,
135.37, 135.45, 148.46 ppm; GCMS: m/z = 337, 291, 183,
174, 153, 128, 109, 91.
To a well stirred solution of salicylaldehyde, diethyl
phosphite and malononitrile (2 mmol, each) in ethanol
(3 mL) was added diethyl amine (10 mol %) and stirring
continued. Upon completion of the reaction, (tlc) water
(10 mL) was added and stirring continued till a free flowing
colourless solid was obtained. It was filtered, washed
successively with water, n-hexane and dried in air.
[1-(4-iso-propylphenyl)-2,2-dicyanoethyl] phosphonic
acid diethyl ester, (6i): IR (CHCl3): 2944, 2833, 2220,
1246,1028 cmÀ1, 1H NMR (300 MHz, CDCl3):
d = 1.11 (t, 3H,
J = 6.9 Hz), 1.28 (d, 6H, J = 6.9 Hz), 1.37 (t, 3H, J = 7.2 Hz),
2
4.2. Spectral data of the representative compounds
2.94 (septet, 1H, J = 7.2 Hz), 3.53 (dd, 1H, JHP = 21.8 Hz,
3JHH = 8.4 Hz), 3.70- 3.78 (m, 1H), 3.95–4.04 (m, 1H), 4.10–
4.23 (m, 2H), 4.48 (t, 1H, JHP = 8.4 Hz, JHH = 8.1 Hz), 7.27
(d, 2H, J = 8.4 Hz), 7.37 (dd, 2H, J = 8.4 & 1.4 Hz); 13C
= 16.04 (d, JCP = 5.4 Hz, CH3),
16.23 (d, 3JCP = 5.8 Hz, CH3), 23.84 (CH3) 25. 46 (CH), 44.44
(d, JCP = 144.7 Hz), 63.08 (d, JCP = 6 Hz, CH2), 64.14 (d,
2JCP = 6.7 Hz, CH2), 110.95 (d, 3JCP = 12.7 Hz, CN), 111. 14 (d,
3JCP = 10.6 Hz, CN), 127.38, 127.40, 127.49, 127.57, 129.18,
129.28, 150.16, 150.20 ppm; GCMS: m/z = 334, 319, 291,
269, 241, 197,171, 156, 138, 111, 91.
[1-(2-Thiophenyl)-2,2-dicyanoethyl] phosphonic acid
diethyl ester, (6 n): IR (CHCl3): 2944, 2216, 1247, 1026,
d = 1.26 (t, 3H,
J = 7.2 Hz), 1.38 (t, 3H, J = 7.2 Hz), 3.87 (dd, 1H,
2JHP = 21.9 Hz, JHH = 6.6 Hz), 3.92–4.25 (m, 4H), 4.46 (dd,
1H, JHP = 8.4 Hz, JHH = 6.9 Hz), 7.10 (dd, 1H, J = 4.8 &
3.9 Hz), 7.33 (t, 1H, J = 2.4 Hz), 7.39 (d, 1H, J = 5.1 Hz); 13C
= 16.18 (d, JCP = 3.7 Hz, CH3),
16.25 (d, JCP = 3.7 Hz, CH3), 26.53 (CH), 39.98 (d,
1JCP = 146 Hz, CH), 63.60 (d, JCP = 6.7 Hz, CH2), 64.44 (d,
3
3
[1-(4-Methylphenyl)-2,2-dicyanoethyl] phosphonic acid
dimethyl ester; (6b): IR (CHCl3): 2987, 2197, 1648, 1256,
1233, 1043 cmÀ1
;
1H NMR (300 MHz, CDCl3):
d
= 2.4 (s,
NMR(CDCl3, 75.4 MHz):
d
3
3H), 3.53 (d, 3H, 2JHP = 10.5 Hz), 3.82 (d, 3H, 2JHP = 10.8 Hz),
3.64 (d, 1H, J = 10.8 Hz), 4.46 (t, 1H, J = 10.5 Hz), 7.23-7.34
1
2
(m, 2H), 7.36 (m, 2H); 13C NMR (75.4 MHz, CDCl3):
1
d
= 21.26, 25.08, 44.12 (d, JCP = 145.14 Hz, CH), 53.30 (d,
2JCP = 7.38 Hz,
OCH3),
54.55
(d,
2JCP = 6.93 Hz,
OCH3),110.88, 111.06, 111.20, 126.97, 127.05, 129.09,
129.17, 129.91, 130.14, 139.45; GCMS: m/z = 294, 278,
213, 167, 115, 110, 93, 79, 63.
[1-(4-Methylphenyl)-2,2-dicyanoethyl] phosphonic acid
di-iso-propyl ester; (6d): IR (CHCl3): 2984, 2256, 2206,
713 cmÀ1 1H NMR (300 MHz, CDCl3):
;
1632, 1381, 1233, 1027 cmÀ1
;
1H NMR (300 MHz, CDCl3):
3
3
3
d
= 0.87 (d, 3H, J = 6.6 Hz), 1.29 (d, 3H, J = 6.3 Hz), 1.36 (dd,
6H, J = 6.1
&
2.7 Hz), 2.39 (s, 3H), 3.44 (dd, 1H,
3
3
2JHP = 18.3 Hz, JHH = 8.4 Hz), 4.38-4.50 (m, 2H), 4.8-4.84
NMR (75.4 MHz, CDCl3):
d
(m, 1H), 7.19–7.26 (m, 2H), 7.31–7.37 (m, 2H); 13C NMR
3
3
2
(75.4 MHz, CDCl3):
d
= 21.25, 22.90 (d, JCP = 6.5 Hz, CH3),
3
3
23.80 (d, JCP = 5.4 Hz, CH3), 23.98 (d, JCP = 3.7 Hz, CH3),
2JCP = 6.7 Hz, CH2), 110.79 (d, 3JCP = 10.5 Hz, CN), 110.91 (d,
3JCP = 10.5 Hz, CN), 125.67, 127.23, 127.26, 129.29, 129.39,
130.61, 130.70 ppm; GCMS: m/z = 298, 233, 205, 190, 162,
138, 123, 111.
[1-(Cyclohexyl)-2,2-dicyanoethyl] phosphonic acid
diethyl ester, (6o): IR (CHCl3): 2933, 2255, 1650, 1450,
1240, 1022, 971 cmÀ1 1H NMR (300 MHz, CDCl3):
3
24.36 (d, JCP = 3.6 Hz, CH3), 25.70 (CH), 44.78 (d,
1JCP = 145.2 Hz, CH), 72.29 (d, JCP = 7.5 Hz, CH), 73.41
2
(2JCP = 7.5 Hz, CH), 111.04 (d, JCP = 12.8 Hz, CN), 111.32
3
3
(d, JCP = 9.8 Hz, CN), 127.56, 127.63, 129.29, 129.37,
129.95, 129.97, 139.19, 139.22 ppm; GCMS: m/z = 334,
277, 250, 187, 143.
;
[1-(3,4-Dimethoxyphenyl)-2,2-dicyanoethyl] phospho-
nic acid diethyl ester; (6g): IR (CHCl3): 2945, 2833, 2221,
d = 1.25-1.42 (m, 11H), 1.70–2.24 (m, 7H), 4.15–4.26
2
3
(m, 4H), 4.37 (dd, 1H, JHP = 14.7 Hz, JHH = 3.7 Hz); 13C
3
1267, 1032 cmÀ1
;
1H NMR (300 MHz, CDCl3):
d
= 1.17 (t,
NMR (75.4 MHz, CDCl3):
d
= 16.30 (d, JCP = 6.0 Hz, CH3),
3
3H, J = 7.2 Hz), 1.38 (t, 3H, J = 7.2 Hz), 3.48 (dd, 1H,
16.36 (d, JCP = 6.0 Hz, CH3), 21.81, 25.68, 26.19, 26.28
(CH2), 31.14, 31.21, 31.37, 31.47, 37.59, 37.63 (CH), 44.19
(d, 1JCP = 140.2 Hz, CH), 62.83 (d, 2JCP = 7.5 Hz, CH2), 63.05
(d, 2JCP = 7.5 Hz, CH2), 111.27, 111.32, 112.08, 112.28 ppm;
GCMS: m/z = 298, 258, 233, 190, 177, 162, 138, 123,
111, 97.
3
2JHP = 21.6 Hz, JHH = 7.8 Hz), 3.74–3.82 (m, 1H), 3.90 (s,
3H), 3.91 (s, 3H), 3.97–4.07 (m, 1H), 4.12–4.24 (m, 2H),
3
3
4.44 (dd, 1H, JHP = 9.0 Hz and JHH = 7.8 Hz), 6.90 (d, 1H,
J = 8.4 Hz and 2.1 Hz), 6.97–7.04 (m, 2H); 13C NMR
(75.4 MHz, CDCl3):
3
d
= 16.19 (d, JCP = 3.8 Hz, CH3), 16.28

752
M.A. Kulkarni et al. / C. R. Chimie 15 (2012) 745–752
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phonic acid diethyl ester, (11b): Colourless solid;
mp = 150–152 8C; IR (KBr) = 3349, 3153, 2189, 1654,
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1419, 1244, 1037, 973 cmÀ1 1H NMR (300 MHz, CDCl3):
;
d
= 1.27 (t, 3H, J = 7.2 Hz), 1.36 (t, 3H, J = 7.2 Hz), 3.83 (d, 1H,
1JHP = 18.5 Hz), 4.03-4.18 (m, 4H), 5.00 (brs, 2H), 6.94 (d,
1H, J = 8.7 Hz), 7.24 (dt, 1H, J = 8.7 Hz & 2.4 Hz), 7.32 (t, 1H,
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(2005) 851.
J = 2.4 Hz); 13C NMR (75.4 MHz, CDCl3):
d = 16.41 (d,
3JHP = 5.2 Hz, CH3), 16.48 (d, JHP = 5.5 Hz, CH3), 35.35 (d,
3
1JCP = 147.7 Hz, CH), 63.12 (d, JCP = 7.5 Hz, CH2), 63.38 (d,
2
2JCP = 7.5 Hz, CH2), 117.70, 117.74, 118.43, 128.99, 129.03,
129.23, 129.29, 148.38, 148.45, 161.64, 164.68 ppm;
HRMS: Mass Calcd for (C14H16O4N2PCl + Na): 365.0434;
Obs. mass: 365.0465.
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Acknowledgement
(f) M.R.H. Mahran, T.S. Hafez, M.M. Henary, Phosphorus, Sulfur, Silicon
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(g) N.M. AbdEl-Rahman, S.T. Rabei, Phosphorus, Sulfur, Siliconand Relat.
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The authors (UVD and MAK) are grateful to UGC, New
Delhi for financial assistance (F. No. 34-362/2008) as well as
for a Junior Research Fellowship, respectively. We are also
thankful to DST and UGC, New Delhi for financial assistance
under DST-FIST and UGC-SAP programme, respectively. We
are sincerely grateful to Prof. A. Srikrishna (IISc, Bangalore)
for fruitful discussions and timely help.
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Appendix A. Supplementary data
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Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.
crci.2012.07.001.
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