A practical and efficient green synthesis of β-aminophosphoryl compounds via the aza-Michael reaction in water

Article abstract of DOI:10.1016/j.crci.2010.03.005

Biphasic systems room temperature imidazolium ionic liquid (RTIL)/water or water as a solvent significantly accelerate the addition of amines to vinylphosphoryl compounds hence opening green and effective synthesis of β-aminophosphoryl compounds in excellent yields over short reaction times. The application of water, being the cheapest and most non-toxic solvent, without any catalyst or co-solvent, is more advantageous as it provides a simple isolation procedure for products having high purity (> 95% according to the NMR data) via simple freeze-drying and does not require extraction with organic solvents. The solubility of the starting phosphorus substrate in water does not play crucial role in the reaction as it was demonstrated using water insoluble diphenylvinylphosphine oxide. In contrast to typical procedures, using a reactant ratio (vinylphosphoryl compound: amine) of 2:1 readily resulted in double phosphorylation of primary amines, including polyamines, in water.

Full text of DOI:10.1016/j.crci.2010.03.005

C. R. Chimie 13 (2010) 964–970
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´
Full paper/Memoire
A practical and efficient green synthesis of
b-aminophosphoryl
compounds via the aza-Michael reaction in water
Ekaterina V. Matveeva a, Pavel V. Petrovskii a, Zinaida S. Klemenkova a,
Natalya A. Bondarenko b, Irina L. Odinets a,
*
a A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,Vavilova str., 28, 119991 Moscow GSP-1, Russian Federation
b State Research Institute of Chemical Reagents and High Purity Substances, Bogorodskii val, 3, 107076 Moscow, Russian Federation
A R T I C L E I N F O
A B S T R A C T
Article history:
Biphasic systems room temperature imidazolium ionic liquid (RTIL)/water or water as a
solvent significantly accelerate the addition of amines to vinylphosphoryl compounds
Received 26 January 2010
Accepted after revision 10 March 2010
Available online 5 May 2010
hence opening green and effective synthesis of
b-aminophosphoryl compounds in
excellent yields over short reaction times. The application of water, being the cheapest and
most non-toxic solvent, without any catalyst or co-solvent, is more advantageous as it
provides a simple isolation procedure for products having high purity (> 95% according to
the NMR data) via simple freeze-drying and does not require extraction with organic
solvents. The solubility of the starting phosphorus substrate in water does not play crucial
role in the reaction as it was demonstrated using water insoluble diphenylvinylphosphine
Keywords:
Green chemistry
Water chemistry
Amines
Nucleophilic addition
Aza-Michael reaction
Phosphaalkenes
oxide. In contrast to typical procedures, using
a reactant ratio (vinylphosphoryl
compound: amine) of 2:1 readily resulted in double phosphorylation of primary amines,
including polyamines, in water.
b-aminophosphoryl compounds
´
ß 2010 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction
One of the main approaches for C–N bond formation
allowing the preparation of a variety of
compounds and their analogues, possessing biological
activity and useful as intermediates in the synthesis of
amino alcohols, amino acids, lactames, and so on, is based
on the aza-Michael reaction, namely the addition of
amines to unsaturated compounds with activated double
bond [4]. In the organophosphorus area, the similar
approach using vinylphosphonates as the starting sub-
b-aminocarbonyl
It is well known that both natural and synthetic
aminophosphonic acid derivatives, being the analogues
of amino acids and competing with them for the active
sites of enzymes, possess high and diverse biological
activities [1]. The type of the activity and the potency of the
compound depend both on the linker length and the
surroundings at the phosphorus and nitrogen atoms.
b
-
Among these compounds, derivatives of
b
-aminopho-
strates and yielding b-aminophosphonates was firstly
sphonic acid, first isolated from Celiate protozoa by
Horiguchi and Kandatsu [2] in 1959, are of great
importance. They demonstrate diverse biochemical prop-
erties such as antibacterial, anti-HIV and protease-
inhibiting activities [3] and possess complexing properties
which are advantageous for selective ionophores or
membrane carrier design [3b].
applied by A.N. Pudovik in 1951 [5]. The further works
based on the above methodology [1,3,6] provided a wide
range of
b-aminophosphonates including quaternary b-
amino-phosphonates which are useful as synthetic nonvi-
ral vector-mediated gene transfer agents [6c], those
bearing perfluoroalkyl groups [6d], and phosphorylated
analogues of putrescine and spermidine [6e], etc. Similarly,
b
-aminophosphine oxides exhibit coordination properties
towards a variety of metals [7] and enantiopure com-
pounds of such a type were used as ligands for ruthenium-
assisted enantioselective transfer hydrogenation of
* Corresponding author.
E-mail address: odinets@ineos.ac.ru (I.L. Odinets).
1631-0748/$ – see front matter ß 2010 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.crci.2010.03.005

E.V. Matveeva et al. / C. R. Chimie 13 (2010) 964–970
965
ketones [8]. Moreover,
b
-aminophosphine oxides are
1,10). Here, 31P and 1H NMR spectra of reaction mixtures
revealed the presence of the starting reactants in the
absence of any side products. To our surprise, in contrast to
the reported data concerning the acceleration of the aza-
Michael addition for non-phosphorus activated alkenes
[11], the reactions at room temperature in ILs were too
sluggish (Table 1, entries 5, 7, 13, 15, 17) or even do not
proceed at all, as in the case of vinylphosphonate 1 in 1-
hexyl-3-methylimidazolium bromide ([hmim]Br) (Table 1,
entry 2). At the same time, addition of water to ionic liquid,
i.e. using the mixture IL/H2O in 1:2 ratio (by weight),
resulted in a drastic increase of the reaction rate and both
counterions of the ionic liquids affected the effectivity
of such systems. Thus, in the case of diethyl vinyl-
phosphonate 1, the reaction with morpholine completed
over 45 min in the system [bmim]Br/H2O while the yield of
the same product was only 82% upon using the system
based on [hmim]Br (Table 1, entries 4 and 3, respectively).
Introduction of hydrophobic counteranions in the IL
structure resulted in a significant decrease of the reaction
rate in the case of 1 and the yields of 2-morpholine-
ethylphosphonate 3a were 60% and 55% for biphasic
systems [bmim]PF6/H2O and [bmim]BF4/H2O, respectively
(Table 1, entries 8 and 6). Primary butylamine was less
useful building-blocks in the synthesis of the correspond-
ing P,N-ligands bearing phosphine donor moieties [9,10].
In any case, the typical reaction conditions for the aza-
Michael synthesis comprise application of amine excess
(either neat or in combination with solvent), basic catalysts
such as EtONa or metal sodium, require elevated tempera-
tures and prolonged reaction times, and hence do not avoid
the polymerization of the starting vinyl substrates, decreas-
ing the yields of the desired products. The substantial
acceleration of amine addition to diphenylvinylphosphine
oxide was observed in MeOH as a protic solvent [10]. The
authors postulated that reactions must involve charged
intermediate which presumable is stabilized and the
protonation step is accelerated in the presence of a proton
source such as the above solvent or amine hydrochloride.
Recently, it was demonstrated that the conjugate
addition of N-nucleophiles to unsaturated compounds
R–CH CH2 (R CO2Et, C(O)Me, CN) proceeds readily at
room temperature in imidazolium ionic liquids (ILs) [11],
biphasic systems IL/water [12] or in water without any
catalyst [13] and results in the final b-aminoderivatives in
the yields close to the quantitative ones. However, in the
so-called ‘‘phosphorus version,’’ before the beginning of
our works, such attempts to optimize the synthesis of
aminophosphoryl compounds using ILs or water as
alternative solvents promoting reaction, were still
limited only by the synthesis of enantiopure -aminopho-
sphine oxide ligands via the reaction of diphenyl- and (R)-
tert-butylphenyl-phosphine oxide with 5–10 molar excess
of the (R)- or (S)-1-phenylethylamine enantiomer in water
(closed ampoule, 110 8C, 7 days) [8].
b
-
reactive and provided 81% of the corresponding b-
aminophosphonate 3b over 45 min in the best system
[bmim]Br/H2O (Table 1, entry 11).
a
b
Under other conditions being equal, the rate of the
amine addition to diphenylvinylphosphine oxide 2 posses-
sing poor water-solubility, was lower comparing with that
for the water soluble phosphonate analogue 1. Moreover,
the effect of the IL nature on the addition rate was different
([bmim]BF4/H2O > [bmim]Br/H2O > [bmim]PF6/H2O), and
the reaction proceeded faster in the system [bmim]BF4/
H2O. As electronic factors for these compounds are close to
each other (sP is 0.965 and 0.955 for Ph2P(O) and
(EtO)2P(O) groups, respectively [15]) and steric factors
should not interfere the reaction, one may assume that the
influence of the phosphorus substrate structure on the
reaction rate is apparently connected with specific
solvatation of the latter in the mixed solvent in use.
Despite mild reaction conditions which provided high
product yields, the main drawback of such biphasic
systems is connected with substantial loss of the target
Taking into account these data, it seems reasonable to
estimate the possibility to use ionic liquids, their
combination with water, or water as suitable solvents
for the ‘green’ and effective synthesis of
b-aminopho-
sphoryl compounds. Herein, we report the results of this
study and suggest an optimized, very simple and high
yielding procedure for
b-aminophosphonates or b-ami-
nophosphine oxides preparation in water without any
catalyst or organic co-solvent and using stoichiometrical
amounts of the reactants, and describe the scopes and
limitations of these reactions.
2. Results and discussion
b-aminophosphoryl compounds over the isolation proce-
dure, i.e., extraction with organic solvents such as diethyl
ether or toluene. At the same time, in water as a sole media
without any co-solvent or catalyst addition of both
morpholine and butylamine to diethyl vinylphosphonate
1 proceeds with the reaction rate commensurable with
that observed in the optimal biphasic system [bmim]Br/
H2O. Moreover, after completion of the reaction, the simple
With regard to higher nucleophilicity of amines in ionic
liquidscomparingwithcommon organic solvents[14] along
withsuccessfulapplicationofILs asapromotingmediumfor
the aza-Michael reaction of non-phosphorus substrates, we
estimated the possibility to use such a medium in the
synthesis of
b-aminophosphoryl compounds. Dietyl vinyl-
phosphonate 1 or diphenylvinylphosphine oxide 2 were
used as representative starting substrates and morpholine
and butylamine asN-nucleophile (Table 1). The differencein
chemical shifts of the phosphorus substrate (17.2 ppm and
24.3 ppm for 1 and 2, respectively) and the product (ca. 30–
31 ppm) allows easy monitoring of the reaction course by
31P NMR spectroscopy.
lyophilization provided the final b-aminophosphonates
with the yields close to the quantitative ones and of high
purity (> 95% according to 1H and 31P NMR data). Even in
the case of diphenylvinylphosphine oxide 2, for which the
rate of the aza-Michael addition in water at room
temperature is significantly lower comparing with that
in the presence of ionic liquid (the system [bmim]BF4/
H2O), the possibility of simple isolation of the product
without loss makes up the deficiency.
In the absence of catalyst, the reaction of 1 with amines
does not proceed in chloroform solution (Table 1, entries

966
E.V. Matveeva et al. / C. R. Chimie 13 (2010) 964–970
Table 1
Influence of the reaction media on the rate of the aza-Michael reaction for vinylphosphoryl compounds.
.
Entry
Phosphorus substrate
Amine
Reaction media
Reaction time
Yield (%)a
1
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
(EtO)2P(O)CH CH2 (1)
Ph2P(O)CH CH2 (2)
Ph2P(O)CH CH2 (2)
Ph2P(O)CH CH2 (2)
Ph2P(O)CH CH2 (2)
Ph2P(O)CH CH2 (2)
Ph2P(O)CH CH2 (2)
Ph2P(O)CH CH2 (2)
Ph2P(O)CH CH2 (2)
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
BuNH2
CHCl3
24 h
0
0
2
[hmim]Br
[hmim]Br/H2O
[bmim]Br/H2O
[bmim]BF4
[bmim]BF4/H2O
[bmim]PF6
[bmim]PF6/H2O
H2O
45 min
45 min
45 min
45 min
45 min
45 min
45 min
45 min
24 h
3
82
100
9
4
5
6
55
2.5
60
100
0
7
8
9
10
11
12
13
14
15
16
17
18
19
20
CHCl3
BuNH2
[bmim]Br/H2O
H2O
45 min
45 min
45 min
45 min
45 min
45 min
45 min
45 min
45 min
36 h
81
79
4
BuNH2
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
[hmim]Br
[hmim]Br/H2O
[bmim]BF4
[bmim]BF4/H2O
[bmim]PF6
[bmim]PF6/H2O
H2O
30
5
45
4
5
8
H2O
100
a
Yield according to 31P NMR spectroscopy.
Therefore, we have moved our attention to the
application of water as a solvent without any additives
for such transformations. It was demonstrated that various
primary and secondary alkylamines add smoothly to
vinylphosphoryl compounds in water at room tempera-
ture, at that the reaction proceeds rapidly in the case of
diethyl vinylphosphonate 1 (generally from 45 mins to 3 h)
[16] and takes more time for the corresponding unsatu-
rated phosphine oxide 2. Indeed, the latter is not soluble in
water, i.e. in this case we use so called ‘on-water’ method
according the definition of Sharpless et al. who demon-
strated that the low miscibility or solubility of organic
compounds in water is not detrimental for their high
reactivity in the presence of water [17]. Hence, the higher
rate of the aza-Michael reaction in the case of vinyl-
phosphine oxide 2 in biphasic systems IL/H2O compared
with that in pure water is obviously connected with phase
transfer properties of onium salts.
The detailed investigation of the aza-Michael addition
has revealed that both the nucleophilic and steric
properties of the amine influence on the reaction rate
which decreased in the series: Alk2NH > AlkNH2 >
ArCH2NH2 for both phosphorus substrates and with an
increase in the bulkiness of the substituents on the
nitrogen atom of the amine. Among secondary amines,
cyclic piperidine was more active than morpholine whose
reactivity was comparable with that of piperid-4-one.
Elongation of the alkyl chain in the alkylamine resulted in a
decrease in reactivity. However, aromatic amines do not
enter the reaction possibly due to a decrease in their
nucleophilic properties. If more than one amine function-
ality was present in the starting reactant, addition to vinyl-
phosphonate in water proceeded readily with participa-
tion of all the amine functionalities.
Thus, in the case of water soluble vinylphosphonate 1,
the reaction with piperidine was complete (quantitative)
just in 7 min at room temperature while the yields of the
corresponding
b-aminophosphonates obtained using
diethylamine, morpholine, n-butylamine and tert-butyla-
mine over the same period of time were 73%, 50%, 25% and
5% [16]. After 45 min, the reaction was complete for
morpholine, Et2NH and n-BuNH2, but for sterically
hindered tert-butylamine the yield of the final addition
product was 78% even after 70 h at r.t. Elongation of the
alkyl chain in the alkylamine resulted in a decrease in
reactivity and at room temperature long-chain aliphatic
dialkylamines (> C8) did not react with vinylphosphonate
1 in water. As mentioned above, in the absence of water
even active amines such as diethylamine did not add to
vinylphosphonate
1 at room temperature over long
reaction times. However, more prolonged reaction time
provided complete conversion under ambient conditions
in all the above cases, including the reactions with
ethylenediamine, meta-xylylenediamine and tris(2-ami-
noethyl)amine which resulted in bis(aminophosphonates)
and tris(aminophosphonate) (Scheme 1) [16].

E.V. Matveeva et al. / C. R. Chimie 13 (2010) 964–970
967
Scheme 1.
For water insoluble vinylphosphine oxide 2, the
reactions with these amines usually required the stirring
of the reaction mixtures for a few days, excluding that with
40% aq. Me2NH (without additional dilution with water)
which proceeded with exothermic effect and afforded
vinylphosphine oxide 4c in quantitative yield over ca
15 min. Fortunately, no side reactions were observed if
reactions of vinylphosphoryl compounds 1,2 with amines
were performed at reflux. Therefore, elevated tempera-
tures could be used to reduce the reaction time. Indeed, at
100 8C the reactions of phosphonate 1 with benzylamine
and N(CH2CH2NH2)3 were complete in 45 min (contrast
with 24 h and 20 h, respectively, at room temperature),
while for less reactive BuNH2 and PhCH(CH3)NH2 about
3 h were required to afford the quantitative conversion
[16]. Performing reactions at reflux was especially
t
Table 2
Influence of reaction temperature on the rate of the aza-Michael addition in water.
.
Entry
R
Amine
Product
Temperature, 8C
Time
Yield, %a
2
3
4
EtO
EtO
EtO
PhCH2NH2
3c
100
100
100
45 min
3 h
100 [16]
100 [16]
100 [16]
L-(-)-PhCH(CH3)NH2
N(CH2CH2NH2)3
L-3d
3e
45 min
5
Ph
4a
100
30 min
100
6
Ph
4b
20
45 min
52
100
20
15 min
15 min
30 min
5 h
100
100
100
100
100
100
7
Ph
Ph
Ph
Ph
Ph
Me2NH
4c
8
Et2NH
4d
4e
100
100
100
100
9
nHexNH2
10
11
nOctNH2
4f
5 h
L-(-)-PhCH(CH3)NH2
L-4g
5 h
12
Ph
4h
4i
100
100
3 h
100
13
Ph
N(CH2CH2NH2)3
45 min
3 h
75
100
a
Yield according to 31P NMR spectroscopy.

968
E.V. Matveeva et al. / C. R. Chimie 13 (2010) 964–970
Scheme 2.
advantageous in the case of vinylphosphine oxide 2 and
under these conditions addition of more reactive second-
ary amines such as piperidine, morpholine and diethyla-
mine completed at the most of 30 min or over a few hours
for other N-nucleophiles. The difference in reactivity of
phosphorus unsaturated compounds 1 and 2 was evident
even at reflux. Thus, at 100 8C, the reaction of phosphine
oxide 2 with L(-)-phenylethylamine and N(CH2CH2NH2)3
completed over 5 h and 3 h, respectively (vs. 3 h and
45 mins for compound 1 [16]) (Table 2).
formed in ca.80% yield, but for complete conversion 20 h
were necessary.
Although the rate of the aza-Michael addition in water
for vinylphosphoryl compounds is a little lower than that
for
amides [13], it proceeds much faster comparing with the
known procedures for the synthesis of -aminophosphoryl
a,b-unsaturated carbocylic acid esters, nitriles or
b
compounds and provide higher yields of the desired
products. Double phosphorylation of primary amines also
proceeds much faster in water compared with MeOH [10]
and does not require application of an additional catalyst
such as amine hydrochloride.
It seems reasonable that acceleration of the aza-
Michael addition in ionic liquids in the presence of water
or in water alone is promoted by both hydrogen bond
formation between the H-atom of water with the oxygen
atom of the phosphoryl moiety increasing the electrophilic
When the starting reactants were used in the ratio 1:1,
only mono adducts were formed in the case of primary
amines and no traces of the corresponding bis-addition
products were observed. However, use of the reactants in
the ratio R2P(O)CH CH2/amine = 2:1 allowed double
phosphonoethylation of primary amines in water. It should
be emphasized that for non-phosphorylated activated
alkenes, double addition to primary amines was not
observed in water as a reaction media [13]. To the best of
our knowledge, no examples of such double phosphono-
ethylation have been observed previously under common
reaction conditions for diethylvinylphosphonate 1. For
diphenylvinylphosphine oxide 2, double addition to
primary amines was performed previously under severe
conditions in the reaction with methylamine (as step-by-
step synthesis, i.e. 10 mol eq. of aq.MeNH2, 1 h, 20–25 8C,
followed by distillation, 76% yield; then addition of 2 (1
eq.), DMSO/H2O, 100 8C, 3 h, 81%) [7], octylamine (neat,
catalyst octylamine hydrochloride, 180 8C, 3 h) [18] or a
character of the
b-carbon atom and that between the H-
atom of the amine with the oxygen atom of water resulting
in increased amine nucleophilic properties.
3. Conclusion
To conclude the results presented, water being the
cheapest and most non-toxic solvent known also as a
‘nature solvent’ significantly accelerates the aza-Michael
reaction for vinylphosphoryl compounds, even those
which are insoluble in water. The synthetic and isolation
procedures are extremely simple and reaction rates are
very high compared with typical toxic or flammable
organic solvents. The reactions can be performed either
under ambient conditions or at reflux. Elevated tempera-
tures do not cause any detrimental effect on the purity of
the final product. The reactions in water allow one to
introduce either one or two phosphorylethyl moieties to
the nitrogen atom in the case of primary amines and to use
all reactive NH-functions in polyamine matrices. Such an
effective, cheap and green approach opens wide possibili-
ties to prepare a variety of biologically active substances,
complexing agents or molecular sensors. In general, the
i
series of C3–C6-alkyl amines (R = nPr, Pr, nBu, sBu, tBu;
sealed tube, MeOH, 80 8C, 8–24 h, or without solvent in the
presence of amine hydrochloride as a catalyst, 140 8C, 4 h)
[10].
At the same time, in water we succeeded in obtaining
the corresponding oligo-phosphonates in excellent yields
using n-butylamine, ethylenediamine, m-xylylenedia-
mine, and tris(2-aminoethyl)amine either under ambient
conditions or at reflux [16]. Despite the lower reactivity of
phosphine oxide 2 compared with phosphonate 1 in water,
the double addition products with phosphine oxide groups
can be also obtained in the yields close to the quantitative
ones as it was illustrated for the reaction with tris-amine as
a representative example (Scheme 2). According to 31P
NMR monitoring, the reaction proceeded via a stepwise
process giving firstly the compound 4i bearing three
phosphine oxide groups. Over 5 h phosphine oxide 5 was
reported approach to
b-aminophosphoryl compounds
being wide in scope, resulted in high yields without any
by-products, proceeded in a benign solvent under simple
reaction conditions with readily available starting materi-
als, satisfies the stringent criteria for classification it as a
click reaction [19].

E.V. Matveeva et al. / C. R. Chimie 13 (2010) 964–970
969
4. Experimental part
4.1.2.2. N-[2-(Diphenylphosphinyl)ethyl]hexylamine
(4e). Yield 95% (after freeze-drying), off-white solid, m.p.
69 8C. 31P NMR (CDCl3): 31.35. 1H NMR (CDCl3):
d d 0.83 (t,
4.1. General remarks
3JHH = 6.5 Hz, 3H, CH3), 1.21 (br. s, 6H, 3CH2), 1.34–1.39 (m,
NMR spectra were recorded with a Bruker AMX-400
spectrometer (1H, 400, 31P, 121 and 13C, 101 MHz) using
residual proton signals of deuterated solvent as an internal
standard (1H, 13C) and H3PO4 (31P) as an external standard.
The 13C NMR spectra were registered using the JMODECHO
mode; the signals for the C atom bearing odd and even
numbers of protons have opposite polarities. IR spectra
were recorded in KBr pellets on a Fourier-spectrometer
‘‘Magna-IR750’’ (Nicolet), resolution 2 cmÀ1, 128 scans.
Melting points were uncorrected.
2H, CH2), 2.06 (br. s, 1H, NH), 2.47–2.53 (m, 4H, P–CH2 and
NH–CH2(CH2)4CH3), 2.92 (dt, JPH = 10.8 Hz, JHH = 7.6 Hz,
2H, PCH2CH2N), 7.41–7.50, 7.65–7.73 (all m, 6H + 4H,
C6H5). 13C NMR (CDCl3):
d 13.74 (s, CH3), 22.24 (s, CH2CH3),
3
3
26.60 (s, CH2(CH2)3CH3), 29.53 (s, CH2CH2CH3), 29.97 (d,
1JPC = 70.8 Hz, P–CH2), 31.38 (s, CH2(CH2)2CH3), 42.56 (s,
NH–CH2(CH2)4CH3), 49.39 (s, NH–CH2–CH2–P), 128.37 (d,
2
3JPC = 11.6, meta-C6H5–P), 130.36 (d, JPC = 9.4 Hz, ortho-
4
C6H5–P), 131.47 (d, JPC = 2.6 Hz, para-C6H5–P), 132.66 (d,
1JPC = 98.9 Hz, ipso-C). IR (KBr; , cmÀ1): 1176 (P = O). Anal.
n
The starting diphenylvinylphospine oxide
2 was
Calcd for C20H28NOP: C, 72.92; H, 8.57; N, 4.25. Found: C,
72.88; H, 8.69; N, 4.17%.
obtained by the known procedure including interaction
of 2-(diphenylphosphinyl)ethanol with phosphoric
trichloride in the presence of triethylamine as reported
in ref. [19]. Other reactants were purchased from Aldrich
and used without further purification.
Physicochemical constants and spectral data of the
known compounds 3a,b [6b], 3c–e [16], 4a,b [20], 4c [21],
and L-4 g [22] fit well the literature data.
4.1.2.3. N-[2-(Diphenylphosphinyl)ethyl]octylamine
(4f). Yield 96% (after freeze-drying), off-white solid, m.p.
35 8C. 31P NMR (CDCl3): 31.33. 1= NMR (CDCl3):
d d 0.84 (t,
3JHH = 6.2 Hz, 3H, CH3), 1.21 (br. s, 10H, 5CH2), 1.78 (br. s,
2H, CH2), 2.48–2.54 (m, 4H, P–CH2 and NH–
CH2(CH2)6CH3), 2.89–2.96 (m, PCH2CH2N), 7.43–7.49,
7.66–7.74 (all m, 6H + 4H, C6H5). 13C NMR (CDCl3):
d
4.1.1. The aza-Michael reaction in ionic liquids and ionic
liquid/water systems
13.88 (s, CH3), 22.44 (s, CH2CH3), 27.06 (s, CH2(CH2)5CH3),
29.01 (s, CH2(CH2)2CH3), 29.26 (s, CH2(CH2)3CH3), 29.66 (s,
CH2(CH2)4CH3), 30.08 (d, JPC = 71.1 Hz, P–CH2), 31.61 (s,
1
In a typical experiment, to a solution of the amine
(1 mmol) (Table 1) in ionic liquid (0.5 g) or biphasic system
ionic liquid (0.5 g)/water (1 ml) was added 1 mmol of diethyl
vinylphosphonate or diphenylvinylphosphine oxide. The
mixture was stirred at room temperature over the time
mentioned in the Table 1. The aliquots were taken off and
analyzed by 31P NMR. For isolation, the reaction solutions
were extracted twice with CH2Cl2. Combine extract was
dried over Na2SO4. After evaporation of the solvent under
reduced pressure, the product was separated from the
residualamountofthecorrespondingionicliquid(inthecase
of [hmim]Br and [bmim]Br) by column chromatography
CH2CH2CH3), 42.69 (s, NH–CH2(CH2)6CH3), 49.50 (s, NH–
3
CH2–CH2–P), 128.50 (d, JPC = 11.7, meta-C6H5–P), 130.52
2
4
(d, JPC = 9.2 Hz, ortho-C6H5–P), 131.61 (d, JPC = 2.6 Hz,
1
para-C6H5–P), 132.81 (d, JPC = 99.0 Hz, ipso-C). IR (KBr; n,
cmÀ1): 1179 (P=O). Anal. Calcd for C22H32NOPÁ0.3H2O: C,
72.70; H, 9.06; N, 3.85. Found: C, 72.50; H, 8.98; N, 3.54%.
4.1.2.4. N-[2-(Diphenylphosphinyl)ethyl]benzenemethana-
mine (4 h). Yield 98% (after freeze-drying), pale yellow oil.
31P NMR (CDCl3):
d d 2.52 (dt,
31.18. 1H NMR (CDCl3):
2JPH = 10.8 Hz, 3JHH = 7.4 Hz, 2H, PCH2), 2.95 (dt,
3
3JPH = 8.2 Hz, JHH = 7.4 Hz, 2H, NCH2CH2P), 3.81 (2H,
(SiO2, CHCl3: methanol, 100:2). The yields of
b-aminopho-
sphoryl compounds after workup range from 65 to 72%.
C5H4N–CH2N), 7.05–7.08, 7.17–7.21 (both m, 1H + 1H,
C5H4N), 7.40–7.47 (m, 6H, C6H5), 7.51–7.55 (m, 1H,
C5H4N), 7.66–7.70 (m, 4H, C6H5), 8.45 (br. s, 1H, C5H4N).
4.1.2. General procedure for b-aminophosphoryl compounds
synthesis via the aza-Michael reaction in water
13C NMR (CDCl3): 29.70 (d, 1JPC = 71.0 Hz, PCH2), 41.86 (s,
d
NCH2CH2P), 54.08 (s, C5H4NCH2N), 121.28 (s, C2), 121.49 (s,
To a solution of the amine (1 mmol) in water (2 ml) at
room temperature was added the appropriate stoichio-
metric amount of diethyl vinylphosphonate 1 or diphe-
nylvinylphosphine oxide 2. The mixture was stirred over
the time mentioned in the Table 2 either at room
temperature or at reflux. Lyophilisation of the reaction
mixture afforded the crude final product with purity > 95%
according to NMR data. If desired, further purification
could be performed via recrystallization from EtOAc for 2-
(amino)ethylphosphine oxides 4a–i, 5. For the experimen-
3
C4), 128.03 (d, JPC = 11.7 Hz, meta-C6H5P), 130.01 (d,
4
2JPC = 9.5 Hz, ortho-C6H5P), 132.32 (d, JPC = 2.6 Hz, para-
C6H5P), 135.79 (s, C3), 148.49 (s, C5), 158.59 (s, C1).
Sample for elemental analysis was obtained by solvent
removing from 13C NMR sample. Anal. Calcd for
C
20H21N2OPÁ1H2O 0.1CDCl3: C, 64.11; H, 6.13; P, 8.18.
Found: C, 63.81; H, 6.08; P, 8.12%.
4.1.2.5. N1-[2-(Diphenylphosphinyl)ethyl]-N2,N2-bis[2-[[2-
(diphenylphosphinyl)ethyl]amino]ethyl]1,2-ethanediamine
(4 i). Yield 95% (after freeze-drying), pale yellow hydro-
tal details for the synthesis of
[16].
b-aminophosphonates see
scopic solid, m.p. 45 8C. 31P NMR (CDCl3):
d
31.84. 1H NMR
4.1.2.1. N-[2-(Diphenylphosphinyl)ethyl]diethylamine
(CDCl3): 2.39–2.46 (m, 6H, PCH2) 2.49–2.59 (m, 12H,
d
(4d). Yield 96% (after freeze-drying), off-white solid, m.p.
NCH2CH2N), 2.84–2.92 (m, 6H, NCH2CH2P), 7.34–7.51,
55 8C [55–56 8C (cyclohexane)]. 31P NMR (CDCl3):
d 31.35.
7.60–7.78 (all m, 18H + 12H, C6H5). 13C NMR (CDCl3):
d
1
Anal. Calcd for C18H24NOP: C, 71.33; H, 8.03; N, 4.65; P,
9.83. Found: C, 71.33; H, 7.95; N, 4.61; P, 10.28%.
29.62 (d, JPC = 70.9 Hz, P–CH2), 42.74 (N–CH2–CH2–P),
46.86 (s, N–CH2–CH2–NH), 53.99 (s, N–CH2–CH2–NH),

970
E.V. Matveeva et al. / C. R. Chimie 13 (2010) 964–970
3
Kafarski, H. Kozlowski, Inorg. Chim. Acta 357 (2004) 1632 ;
(c) M.S. Rahman, M. Oliano, H. Kuok, Tetrahedron: Asymmetry 15
(2004) 1835.
128.50 (d, JPC = 11.7 Hz, meta-C6H5–P), 130.52 (d,
2JPC = 9.2 Hz, ortho-C6H5–P), 131.61 (d, JPC = 2.6 Hz, para-
C6H5–P), 132.81 (d, JPC = 99.0, ipso-C). IR (KBr,
4
1
n
, cmÀ1):
[4] G. Cardillo, C. Tomasini, Chem. Soc. Rev. 25 (1996) 117.
[5] A. N. Pudovik, Dokl. Akad. Nauk USSR 80 (1951) 65.
[6] (a) E.S. Gubnitskaya, L.P. Peresypkina, L.I. Samaray, Russ. Chem. Rev. 59
(1990) 807 (and references cited therein) ;
1175 br. (P = O). Anal. Calcd for C48H57N4O3P3Á2H2O: C,
66.50; H, 7.09; N, 6.46. Found: C, 66.43; H, 6.97; N, 6.39%.
(b) R.A. Cherkasov, V.I. Galkin, N.G. Khusainova, O.A. Mostovaya, A.R.
Garifzyanov, G.Kh. Nuriazdanova, N.S. Krasnova, E.A. Berdnikov, Russ. J.
Org. Chem. 41 (2005) 1481 ;
(c) E. Gue´nin, A.-C. Herve´, V. Floch, S. Loisel, J.-J. Yaouanc, J.-C. Cle´ment,
C. Ferec, H. des Abbayes, Angew. Chem. Int. Ed. 39 (2000) 629 ;
(d) W. Cen, Y. Shen, J. Fluorine Chem. 72 (1995) 107 ;
(e) J. Mortier, A.-D. Fortineau, M. Vaultier, Phosphorus, Sulfur, Silicon
149 (1999) 221.
4.1.2.6. N1,N1-Bis[2-[bis[2-(diphenylphosphinyl)ethyl]ami-
no]ethyl]-N2,N2-bis[2-(diphenylphosphinyl)ethyl]-1,2-etha-
nediamine (5). Yield 96% (after freeze-drying), pale yellow
hydroscopic solid, m.p. 67 8C. 31P NMR (CDCl3):
s). 1H NMR (CDCl3):
2.16–2.18 (m, 6H, NCH2CH2N), 2.26–
d 30.83 (br.
d
2.33 (m, 18H, PCH2 and NCH2CH2N), 2.69–2.74 (m, 12H,
NCH2CH2P), 7.38–7.43, 7.67–7.72 (all m, 36H + 24H, C6H5).
[7] A.N. Turanov, V.K. Karandashev, N.A. Bondarenko, E.M. Urinovich, E.N.
Tsvetkov, Russ. J. Inorg. Chem. 41 (1996) 1658.
[8] M. Maj, K.M. Pietrusiewicz, I. Suisse, F. Agbossou, A. Mortreux, Tetra-
hedron: Asymmetry 10 (1999) 831.
[9] K.K. Hii, M. Thornton-Pett, A. Jutand, R.P. Tooze, Organometallics 18
(1999) 1887.
[10] M.S. Rahman, J.W. Steel, K.K. Hii, Synthesis (2000) 1320.
[11] J.S. Yadav, B.V.S. Reddy, A.K. Basak, A.V. Narsaiah, Chem. Lett. 32 (2003)
988.
13C NMR (CDCl3): 26.56 (d, 1JPC = 69.0 Hz, PCH2), 45.71 (s,
d
NCH2CH2P), 46.61 (s, NCH2CH2N), 52.85 (s, NCH2CH2N),
128.54 (d, 3JPC = 11.7 Hz, meta-C6H5P), 130.54 (d, 2JPC = 9.5,
4
ortho-C6H5P), 131.56 (d, JPC = 2.2 Hz, para-C6H5P), 133.06
1
(d, JPC = 98.3, ipso-C). IR (KBr,
n
, cmÀ1): 1174 br. (P=O).
Anal. Calcd for C90H96N4O6P6Á3H2O: C, 68.87; H, 6.55; N,
[12] Li-W. Xu, J.-W. Li, S.-Li Zhou, C.-Gu Xia, New. J. Chem. 28 (2004) 183.
[13] B.C. Ranu, S. Banerjee, Tetrahedron Lett. 48 (2007) 141.
[14] L. Crowhurst, N.L. Lancaster, J.M. Pe´rez Arlandis, T. Welton, J. Am. Chem.
Soc. 126 (2004) 11549.
3.57. Found: C, 68.89; H, 6.51; N, 3.40%.
[15] M.I. Kabachnik, T.A. Mastryukova, I.M. Aladzheva, P.V. Kazakov, L.V.
Kovalenko, A.G. Matveeva, E.I. Matrosov, I.L. Odinets, E.S. Petrov, M.I.
Terechova, Teor. Exper. Khim. 27 (1991) 284.
[16] E.V. Matveeva, P.V. Petrovskii, I.L. Odinets, Tetrahedron Lett. 49 (2008)
6129.
[17] S. Narayan, J. Muldoon, M.G. Finn, V.V. Fokin, H.C. Kolb, K.B. Sharpless,
Angew. Chem. Int. Ed. 44 (2005) 3275.
[18] M.I. Kabachnik, T.Ya. Medved’, Yu.M. Polikarpov, K.S. Yudina, Izv. Akad.
Nauk SSSR, Ser. Khim. (1962) 1584.
Acknowledgements
This work was supported by Program of Chemistry and
Material Science Division of RAS and program of President
of Russian Federation ‘‘For Young PhD scientists’’ (No MK-
425.2010.3).
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