Synthesis of new liophilic functionalized aminomethylphosphine oxides and their acid-base and membrane-transport properties toward acidic substrates

Article abstract of DOI:10.1134/S1070363209090114

A large number of new lipophilic mono- and bisphosphinylamines including those possessing additional potential centers of coordination was synthesized on the basis of the Kabachnik-Fields reaction, and acid-base and membrane transport properties of the sy

Full text of DOI:10.1134/S1070363209090114

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 9, pp. 1835–1849. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © R.A. Cherkasov, A.R. Garifzyanov, A.S. Talan, R.R. Davletshin, N.V. Kurnosova, 2009, published in Zhurnal Obshchei Khimii,
2009, Vol. 79, No. 9, pp. 1480–1494.
Synthesis of New Liophilic Functionalized
Aminomethylphosphine Oxides and Their Acid–Base
and Membrane-Transport Properties Toward Acidic Substrates
R. A. Cherkasov, A. R. Garifzyanov, A. S. Talan, R. R. Davletshin, and N. V. Kurnosova
Kazan State University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia
e-mail: rafael.cherkasov@ksu.ru
Received April 7, 2009
Abstract—A large number of new lipophilic mono- and bisphosphinylamines including those possessing
additional potential centers of coordination was synthesized on the basis of the Kabachnik–Fields reaction, and
acid–base and membrane transport properties of the synthesized compounds toward the mono- and polybasic
carboxylic acids were studied. By their basicity all the synthesized aminophosphine oxides were shown to be
inferior to their aliphatic amine precursors. Introduction of the second phosphinyl group so strongly decreases
the basicity that the determination of pKa by potentiometric method becomes impossible. Interrelation between
the structure of aminophosphinyl carrier and substrate and the efficiency of the membrane transport of acidic
substrates are discussd.
DOI: 10.1134/S1070363209090114
A vital problem of contemporary analytical,
coordination and environmental chemistry is the
creation of new highly effective extractants for the
separation and concentration of the mixtures of
substrates of different origin, both natural and
technogenic. An acknowledged and promising method
of solution of this problem is the application of the
membrane technology based on the liquid impregnated
membranes. In a large series of investigations [1–13]
we have established high efficiency and selectivity of
the membrane transfer of different substrates of
organic and inorganic nature at the application of
functionalized phosphoryl compounds, and first of all
aminophosphoryl compounds, the analogs of natural
amino acids. Thus, the high efficiency was shown of
the membrane transport of the ions of alkaline and
alkaline earth metals by phosphorylated azapodands
[11], and of the transfer through the liquid membranes
by mono- and diphosphorylated amines of mono- and
polybasic carboxylic acids [12, 13].
aminophosphine oxides are stable in acidic and
alkaline media and show a high rate of transfer of
monobasic (acetic) and dibasic (glutaric) acids that we
have explained by the formation in the source aqueous
phase of strong “substrate–carrier” N-complexes with
the participation of one or two basic centers of the
carrier. As to polybasic hydroxy acids, tartaric and
citric, a sharp drop in the transfer flow rate for these
substrate is connected obviously with the presence in
them of highly hydrophilic hydroxy and carboxy
groups not connected with the basic centers of the
carrier and capable to form strong hydrogen bonds
with water molecules to retain the formed complexes
in the source aqueous phase.
For further examination of the relationship between
structure of aminophosphine oxide carriers and their
membrane-transport properties with respect to acid
substrates we perfomed the purposeful synthesis of
new aminophosphoryl compounds containing one or
two aminomethylphosphinyl groups and possessing an
increased lipophilicity due to the introduction of long-
chain substituents to the nitrogen and phosphorus
atoms. Their formulas and characteristics are given in
Table 1. In addition, it seems important to trace the
effect of the introduction to their molecules of
additional functional groups capable of coordination
Among the many aminophosphoryl compounds we
have investigated the most suitable for the transfer of
acids we believe to be the aminophosphine oxides with
one or two phosphinyl groups located at different
distances from the carrier basic center, the nitrogen
atom [13]. Due to the absence of labile ester bonds the
1835

1836
CHERKASOV et al.
Table 1. Aminophosphoryl compounds
Comp. no.
Formula
mp, °С
n2D0 (nDt)
δP, ppmа
48
Rfb
O
28
–
0.65
I
NHC H
(C H ) P
8
17
6
13 2
O
O
O
O
c
c
c
c
c
c
1.4870
1.4652
1.4648
1.4710
45
47
47
44
0.58
0.66
0.53
0.57
II
(C H ) P
NH
6
13 2
III
IV
V
N(C H
)
(C H ) P
8
17 2
6
13 2
N(C H )
(C H ) P
4
9 2
6
13 2
NHC H
(C H ) P
4
9
6
13 2
O
1.4729
1.4719
–
25
45
48
43
27
0.54
0.57
0.68
0.61
0.4
VI
(c-
N(i-Oct)
2
C H O) P
6
11
2
O
VII
VIII
IX
NHC H
(C H ) P
4
9
8
17 2
O
O
36
NHC H
(C H ) P
8
17
8
17 2
c
1.4760
1.4749
NH
(C H ) P
8
17 2
O
c
c
X
(p-Tol) P
NHC H
2
8
17
O
O
O
O
1.4650
45, 31
XI
(C H ) P
N
P(OC H -i)
2
8
17 2
3
7
C H
4
9
O
c
43, 26
46
XII
N
(C H ) P
P(OC H )
4 9 2
8
17 2
C H
4
9
O
89
–
0.15
XIII
N
N
(C H ) P
P(C H )
6 13 2
6
13 2
OH
O
O
c
c
c
c
1.4520
1.4729
1.5190
1.4652
25
0.52
0.53
0.45
0.46
XIV
XV
(C H O) P
P(OC H )
4
9
2
4
9 2
C H
8
17
O
O
O
O
44
(C H ) P
N
P(C H
)
6
13 2
6
13 2
C H
8
17
O
45, 27
49
XVI
XVII
(C H ) P
N
P(p-Tol)
6
13 2
2
C H
8
17
O
(C H ) P
N
C
OC H
2 5
6
13 2
C H
4
9
O
c
1.4728
–
47d
53
0.60
0.51
XVIII
XIX
OH
(C
(C
H
) P
N
10 21 2
C H
6
13
O
O
65
H
) P
N
C
OH
10 21 2
C H
4
9
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009

SYNTHESIS OF NEW LIOPHILIC FUNCTIONALIZED AMINOMETHYLPHOSPHINE OXIDES
Table 1. (Contd.)
1837
Comp. no.
Formula
mp, °С
n2D0 (nDt)
δP, ppmа
Rfb
O
O
O
C
29
–
53
0.46
XX
(C H ) P
N
OH
8
17 2
C H
4
9
O
c
53
0.4
XXI
(C H ) P
N
C
OH
6
13 2
C H
4
9
O
69
53e
XXII
NH
(C
(C
H ) P
10 21 2
N
O
O
80
82
–
46
43
0.30
0.15
XXIII
XXIV
NH(CH ) HN
H
) P
P(C
H )
2 4
10 21 2
10 21 2
O
O
NH(CH ) HN
(C H ) P
P(C H )
8 17 2
2 6
8
17 2
a
b
External reference 85% H3PO4, solvent toluene. Most of Rf values of the obtained aminophosphoryl compounds were measured with
c
d
the eluent chloroform–acetone (3:1), Silufol UV 254. External reference 85% H3PO4, solvent acetonitrile. External reference 85%
H3PO4, solvent chloroform. e Undistillable viscous liquid (oil).
with the proton substrates, that, in our opinion, could
facilitate or, conversely, hinder the formation of the
substrate–carrier complex, which should affect the
value of the flow at the transport through the
membrane. The revealed regularities could obviously
serve as a basis for purposeful introduction into the
molecule of the carrier of certain functional groups and
thus regulate consciously the efficiency and selectivity
of the membrane transport of substrates with a certain
structure.
constraints to the use of column chromatography for
the highly lipophilic objects we developed an original
“oxalate” method for purification of the amino-
phosphoryl compounds that consists in the treatment of
the crude aminophosphine oxide with oxalic acid taken
in a small excess, recrystallization of the formed salt,
and release of the phosphorylated amine by a weak
alkalinization. The purity of the aminophosphoryl
compounds thus obtained (control by TLC and NMR
31P) was almost 100%. In addition, we used the
method of microwave activation of the Kabachnik–
Fields reaction, which reduces the reaction duration
from hours to 10–20 minutes.
For the synthesis of target substances I–XXIV we
used the classical one-pot Kabachnik-Fields method
emp;oying ternary system of dialkylphosphinous acid–
form-aldehyde–amine as well as the multistep methods
of synthesis developed by us specifically for this
purpose. We carried out a investigation of the reaction
conditions (solvent, catalyst, temperature) with respect
to the reactivity of reagents and the stability of the
target products. Moreover, owing to technological
Synthesis of aminophosphoryl compounds I, II, V,
VII–X containing a phosphoryl center and amino-
methyl group with a secondary nitrogen atom was
carried out for 1–4 h using the three-component
Kabachnik–Fields reaction with p-toluenesulfonic acid
as a catalyst, in boiling benzene or toluene as solvents.
Boiling temperature of solvent,
O
H
O
TsOH
+
P
P
CH2O + HN
N
Benzene, toloene, o-xylene,
acetonitrile
The completion of the reaction was monitored by
TLC, by the amount of formed water collected in a
Dean-Stark trap, and by 31P NMR spectroscopy. The
structure of the compounds was proved by NMR (1H,
31P) and IR spectroscopy, elemental analysis, and mass
spectrometry. The IR spectra of aminophosphoryl
compounds contain a signal in the region of 1100–
1200 cm–1 characteristic of P=O group. The com-
pletion of the reaction with secondary amines was
determined by the disappearance of the NH signal at
~3300 cm–1. In the 31P NMR spectra the completion of
the reaction is shown by the appearance of a singlet at
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009

1838
CHERKASOV et al.
44–49 ppm characteristic of the most aminophosphoryl
compounds with phosphine oxide structure [2, 3]. In
some cases this signal is accompanied by a signal at
~51 ppm indicating the presence in the reaction
mixture of hydroxymethylphosphine oxide, the product
of the competitive route along Abramov’s reaction. In
the spectra of the aminomethylphosphonates and
compound X with the acceptor p-tolyl group at the
phosphorus atom the signal of parent product is shifted
upfield to 22–30 ppm in agreement with the published
data [2].
In the 1H NMR spectra of all obtained
aminophosphoryl compounds of this group were ob-
served a typical doublet of the methylene groups P–
CH2 and a triplet of methylene group at the nitrogen
atom N–CH2, or a multiplet of N–CH proton. More
detailed identification of signals is not possible
because of the presence of multiplets and broad singlets
of long-chain hydrocarbon substituents.
elemental analysis. At the same time analogous opera-
tion at the synthesis of dihexyl-N-octylaminophos-
phine oxide I (heating the reaction mixture without a
solvent to 210°C) does not prevent the side reaction
giving the hydroxymethylphosphine oxide. Moreover,
after prolonged heating the strong tarring of the
mixture is observed, and in the NMR spectra appear
additional signals indicating formation of oxidation
products. The same pattern is observed also in the case
of dihexyl-N,N-dioctylaminomethylphosphine oxide III.
We succeeded in preventing the undesirable side
reactions of formation and decomposition of hydroxy-
methylphosphine oxides in the synthesis of amino-
phosphine oxides with the tertiary nitrogen atom by
replacing the nonpolar solvents by the more polar
acetonitrile. We suggest that in this case in the reaction
with secondary amine the intermediately formed
iminium cation is better stabilized. Monitoring the
reaction course by tracing isolation of water in the
Dean–Stark trap becomes impossible, and the
completion of the synthesis was checked by TLC and
by NMR spectroscopy. The reaction was carried out at
the solvent boiling point in the presence of catalytic
amount of p-toluenesulfonic acid. In all cases in aceto-
nitrile the reaction proceeded successfully in 2–4 h, the
signals of side product hydroxymethylphosphine oxide
in the NMR spectra were not registered. For removing
the catalyst, into the reaction mixture after the reaction
completion was added sodium carbonate at stirring and
heating to 50°C. Then the mixture was washed with
water, organic fraction was dried over magnesium
sulfate, filtered, and then evaporated to dryness. The
products were obtained in high yield (85%) in the form
of white crystals or light oily substance; in the latter
case we used “oxalate” method for the purification of
aminophosphoryl compounds.
The synthesis of aminophosphoryl compounds in
the described above conditions in some cases is com-
plicated by the formation of hydroxymethylphosphine
oxide. This product of the side reaction is formed in
10–30% yield. The separation of these substances from
mixtures by traditional methods of distillation or
recrystallization was not always possible, and we used
the new method we developed: preparation of the set
of aminophosphoryl compound with oxalic acid, recrys-
tallization of the salt, and isolation of the target amino-
phosphoryl compound by weak alkalinization. This
method of purification can be used for oily amino-
phosphoryl compounds; it replaces effectively the
time-consuming method of column chromatography.
The reaction with the participation of secondary
amines in nonpolar solvents proceeds less actively than
with primary amines since the iminium intermediate
formed in the course of the reaction [14] is less stable
in the nonpolar solvent than imine, and it is rapidly
decomposed into the initial formaldehyde and second-
dary amine. By the example of dihexyl-N,N-dibutyl-
aminomethylphosphine oxide IV we showed that
regardless the duration of stirring the reagents in
boiling o-xylene the ratio of the side dihexyl-α-hyd-
roxymethylphosphine oxide (δ 51 ppm) and amino-
phosphine oxide IV (δ 47 ppm) reaches, according to
the data of 31P NMR spectroscopy, 3:4 and is not
changed. However, after removing the solvent in a
vacuum and heating the mixture to 210°C the reaction
proceeds to the end with formation of amine IV, as
follows from the data of NMR spectroscopy and
The information that appeared recently in the literature
on the microwave activation of the Kabachnik–Fields
reaction with the participation of ketones and
phosphites [15–17] impelled us to use this method for
the preparation of lipophilic aminomethylphosphine
oxides by the three-component Kabachnik–Fields
reaction with paraform and respective amines using an
ordinary cooking microwave furnace at the maximum
regime of heating (720 W). In this case we, however,
encountered the same complications which were
characteristic for the syntheses of aminophosphine
oxides in nonpolar solvents described above. Thus, the
reaction with the dioctylphosphinous acid, paraform
and dibutylamine, according to the data of NMR
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SYNTHESIS OF NEW LIOPHILIC FUNCTIONALIZED AMINOMETHYLPHOSPHINE OXIDES
1839
spectra, proceeded with the formation of two products:
~20% of hydroxymethylphosphine oxide and ~80% of
the desired aminophosphine oxide IV. After heating
for 30 min the signal of the by-product did not
disappear. A similar situation was observed also in the
case of didecylphosphinous acid and di-2-ethylhexyl-
amine: the formation of the by-product reached approxi-
mately 30%, and the ratio of the target compound and
by-product did not change at the prolonged heating
(50 min).
The conditions we found for the three-component
Kabachnik–Fields reaction for obtaining monophos-
phorylated amines we applied to the synthesis of diphos-
phorylated amines XII–XVI. In this case for obtaining
symmetrical diphosphinylamines XIV and XV the
appropriate hydrophosphoryl compounds, formaldehyde
and primary amine in the ratio 2:2:1 were introduced
into the reaction. The most suitable solvents for the
synthesis of the phosphonate derivatives XII and XIV
proved to be benzene and toluene; the best results at
the synthesis of bis-phosphine oxides XV and XVI
were reached at the use of acetonitrile as the medium.
These complications do not appear in the reactions
of primary amines: the almost quantitative yield of the
final aminophosphoryl compounds II and VII is
achieved at heating for ~20 min. Obviously, the
Kabachnik–Fields reaction with the participation of
secondary amines is controlled by steric factors. While
the reaction with dibutylamine in the medium of a
nonpolar solvent or without it proceeds readily, in the
case of secondary amines with the bulky radicals
(octyl, 2-ethylhexyl) the rates of formation of imines
and products of their further hydrophosphorylation
(“imine” way of Kabachnik–Fields reaction) and of
Abramov reaction (“hydroxyphosphine oxide” way)
apparently become comparable.
The synthesis of asymmetrical diphosphinylamines
was carried out in two stages. The monoaminophos-
phoryl compound formed during the first stage was
used without purification and isolation in the reaction
with paraform and the corresponding hydrophosphoryl
compound. This procedure allowed the prevation of
the formation of hydroxymethylphosphoryl compound.
Thus, by the two-stage version the synthesis was per-
formed of asymmetrical aminophosphoryl compound
XII: to the preliminarily obtained N-[(dibutoxyphos-
phoryl)methyl]butylamine dissolved in acetonitrile
were added phosphinous acid and paraform:
−H2O
O
O
+ CH2O + H2NC4H9
NHC4H9
(C4H9O)2P
(C4H9O)2P
H
−H2O
O
H
O
O
N
O
NHC4H9
(C4H9O)2P
+ CH2O + (C8H17)2P
(C8H17)2P
P(OC4H9)2
C4H9
XII
The second stage of reaction, as follows from the
data of 31P NMR spectroscopy, proceeds completely.
This is confirmed by the presence of two signals: a
peak at 48 ppm corresponding to the phosphine oxide
phosphorus atom, and a signal at 26 ppm which
belongs to phosphorus atom of phosphonate group.
data of 31P NMR spectra, the formation of
dioctylphosphinyl compound XXIV proceeds without
any complications: one signal at 47 ppm is observed
and the signal of the initial compound is absent.
Compound XXIII was analogously prepared when
didecylphosphinous
acid
was
used
as
a
For the synthesis of N,N'-bisdiaminophosphine
oxides XXIII and XXIV we introduced the respective
primary 1,4-and 1,6-diamines into the reaction with
phosphinous acids and paraform employing general
procedure with toluene as a solvent. According to the
hydrophosphoryl component. However, in this case for
an increase in the solvent polarity we used 1:2 mixture
of DMF with benzene, which allowed not to elevate
the reaction temperature and thus to avoid tarring. In
the 31P NMR spectrum one signal at 46 ppm was fixed.
O
O
O
TsOH
P(R)2
NH(CH2)nNH
2 (R)2P
+ 2 CH2O + NH2(CH2)nNH2
(R)2P
−2 H2O
H
R = C10H21, n = 4 (XXIII); R = C8H17, n = 6 (XXIV).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009

1840
CHERKASOV et al.
We developed two methods for the synthesis of
binding the formed hydrochloric acid. The remaining
0.05 mol of hydrochloric acid had to perform the role
of a catalyst. The reactions were completed approxi-
mately in 2 h. By the data of 31P NMR spectra
the yield of the product is close to quantitative, only
one peak appeared at –53 ppm of compound XIX or
XX.
aminophosphoryl compounds with the aminoacid
group. The first was the traditional Kabachnik–Fields
reaction: interaction of phosphinous acid with the
carbonyl component and the corresponding ammonium
chloride derivative of the acid in acetonitrile. Into the
reaction mixture 0.45 mol of K2CO3 was added for
O
O
H
ΑΝ, K2CO3
O
O
+ CH2O + Cl−H2N+CH2C
C4H9
R2P
R2P
N
C OH
−2 H2O, −KCl
OH
C4H9
XIX, XX
R = C10H21 (XIX), C8H17 (XX).
The second method consists in the “construction”
of the aminoacid with the use of aminophosphine
oxide as the amino component. This strategy is based
on the two-stage process, which makes it possible also
to obtain aminophosphine oxides with the ester group.
the chromatogram; splitting of this signal of ion
current probably indicates the formation of a
sufficiently stable dimer which also is fixed in the
mass-spectrum. Furthermore, a peak of the protonated
molecule is also seen (474.10), of its dimer (947.19),
and of the complex with didecylphosphoryl cation
(810).
O
O
(C6H13)2P
NHC4H9 + BrCH2
C
OC2H5
For the synthesis of promising membrane-transport
carriers and extractants containing as the additional
potential center of coordination the hydroxy group, we
brought aminoalcohols to the Kabachnik–Fields
reaction. The reaction with the participation of
ethanolamine in the medium of acetonitrile afforded
the final product in the form of a viscous liquid, whose
salt with oxalic acid was obtained, recrystallized, and
transformed into aminophosphoryl compound XVIII
to which in the 31P NMR spectrum corresponded a
singlet at 51 ppm.
V
ΑΝ, K2CO3
−KBr
O
O
(C6H13)2P
N
C OC2H5
C4H9
XVII
The aminophosphine oxide V obtained by this
method undergoes reaction with ethyl bromoacetate in
acetonitrile with 1.5 molar excess of K2CO3. In the 31P
NMR spectrum to the reaction product XVII, the
phosphorylated ester of aminoacetic acid, corresponds
a singlet at 53 ppm, the formation of other phosphorus-
containing products was not registered.
For introduction into this molecule of the second
phosphoryl group to obtain diphosphorylated amino-
ethanol XIII we used the two-stage version of the
reaction in order to avoid the formation of hydroxy-
methylphosphine oxide.
The structure of this compound was studied also by
GC–MS method. One peak at 2.72 min is present on
O
O
TsOH
OH
OH
NH
O
(C6H13)2P
(C6H13)2P
O
H N
2
+ CH2O +
OH
−H2O
H
O
O
H
TsOH
N
(C6H13)2P
P(C6H13)2
OH
(C6H13)2P
NH
(C H ) P
+ CH2O +
6
13 2
−H2O
XIII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009

SYNTHESIS OF NEW LIOPHILIC FUNCTIONALIZED AMINOMETHYLPHOSPHINE OXIDES
1841
In the first stage for the condensation of dihexyl-
phosphinite with paraform and aminoethanol a 1:2
mixture of DMF with benzene was used as a solvent.
Further the solvent was distilled off and the second
part of the synthesis, the reaction of dihexyl-N-2-
hydroxyethylaminomethylphosphine oxide with para-
form and dihexylphosphinous acid, was carried out in
the medium of acetonitrile. In the 31P NMR spectrum
of compound XIII recrystallized from hexane a singlet
is present at 46 ppm.
basis for studying their extraction and membrane
transport properties toward diverse substrates. We
assumed that introduction of additional functional
groups capable to form both N-complexes with acidic
substrate and complexes with metal ions would give a
possibility to reveal the interrelation between their
structure and practically useful properties including the
studied membrane transport, extraction and, later,
ionofor properties, etc. This, in turn, would open a way
to the selection of complementary pairs substrate–
carrier and thus would allow to optimize the processes
of the membrane and liquid extraction of the objects of
different nature.
We believe that the promising pathway for the
creation of the polyfunctional carriers of acids consists
in the introduction into the molecule of an amino-
phosphoryl compound, together with the aminomethyl
group, of other organonitrogen basic function, for
example, pyridine ring. We undertook an attempt of
the synthesis of aminophosphine oxides on the basis of
α-aminopyridine in o-xylene at heating during five
days. However, reaction did not proceed to the end, the
formation of by-products was observed, and it was
impossible to isolate the final product even by the
“oxalate” purification. Under the milder conditions, at
the use of acetonitrile and dioxane as solvents,
according to the 31P NMR spectra the reaction
proceeded completely enough, although not to the end
(in the acetonitrile approximately up to 10% of
phosphinous acid was present, in dioxane, about 5%);
in this case the formation of by-products, first of all, of
hydroxyphosphine oxide, was not observed. After
removal of the solvent on the rotary evaporator the
residue was dissolved in benzene and washed initially
with aqueous alkali and then with water. According to
the data of TLC and 31P NMR spectroscopy (singlet at
30.8 ppm) the product did not contain foreign matter.
The yield of pure didecyl-β-(2-pyridyl)aminophos-
phine oxide XXII was about 70%.
The protolytic equilibria with the participation of
aminophosphoryl compound occur in all the processes
at their practical appliction (membrane transport, extrac-
tion, and complex formation). Therefore we determined
the ionization constants (pKa) of the conjugate acids of
the aminophosphine oxides obtained by us.
Earlier [2, 18] we determined the ionization
constants of a wide range of α-aminophosphonates in
water and in the water–2-propanol media with the
water content 50 and 25 vol %, and revealed linear
correlations between the values of pKa determined in
the media with different content of water. For the
comparability of these results we also have determined
the ionization constants of a series of newly syn-
thesized aminophosphoryl compounds in the medium
of aqueous 2-propanol containing 50 vol % of water to
ensure a sufficiently high solubility of the compounds
investigated. The values of pKa of lipophilic α-
aminophosphine oxides and a number of the func-
tionalized derivatives are given in [19].
For the estimation of the effect of introduction of
phosphinyl groups to the amine molecule we deter-
mined also the ionization constants of aliphatic and
aromatic amines of different structure, mainly the
amine precursors of the corresponding aminophos-
phoryl compound. The values of their pKa differ little
from each other and vary in the range of 8–10 units.
The analysis of the influence of the aminophosphoryl
compound structure on its basicity in the investigated
series allows to derive a number of the most general
regularities connecting the structure and the basicity of
the studied lipophilic aminophosphoryl compounds.
First of all, it should be noted that like α-amino-
phosphonates [2], the α-aminophosphine oxides are
considerably inferior by the basicity to their pre-
cursors, the non-posphorylated amines: the pKa values
of amines and the corresponding aminophosphine
N
O
(C10H21)2P
+ CH O +
H2N
2
H
N
O
TsOH
N
(C10H21)2P
−H2O
XXII
The method of the synthesis of the first repre-
sentative of γ-aminophosphoryl compounds, the diphos-
phorylated amine XI, we described earlier [13].
The compounds of phosphine oxide and phos-
phonate structure (Table 1) we synthesized form a
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009

1842
CHERKASOV et al.
Table 2. Difference in basicity of aminophopshine oxides
and parent amines
from the acidic media as compared to the widely
utilized at present aliphatic amines or the neutral
organophosphorus reagents. Thus, a new possibility
appears of creating on their basis reagents with the
specific properties like enhanced selectivity.
Amine
Aminophosphine
ΔpKa
oxide
V
C4H9NH2
9.74 − 5.70 = 4.04
9.49 − 5.51 = 3.98
9.68 − 5.65 = 4.13
9.60 − 4.47 = 5.13
8.87 − 3.90 = 4.97
Earlier we established that α- and β-
aminophosphoryl compounds could be used as
selective extractants of the ions of noble metals [3–5]
and as ionophores in the ion-selective electrodes [1].
Also, they are of undoubted interest as carriers in the
processes of the membrane extraction of organic and
inorganic substrates [6, 20]. A study of the influence of
structure of the functionalized phosphoryl carriers on
the efficiency of the membrane transport of proton-
donor substrates [21] and of interphase ion transfer of
metals [5, 6] made it possible to establish the influence
of “additional” donor functional groups on the ability
of phosphoryl extractants to complexation. A similar
comparison for mono- and diphosphorylated phos-
phine oxides and phosphonates as the membrane
carriers of proton-donor substrates has not been per-
formed so far.
C8H17NH2
I
o-C6H11NH2
IX
(C4H9)2NH
IV
HOCH2CH2(C6H13)NH2
XVIII
oxides differ approximately by 4 units in the case of
primary amines and by 5 units for the secondary
amines. This change in the basicity of amines as a
result of their phosphorylation is completely
undestandable if we consider the significant electron-
acceptor effect of the phosphoryl group. For the
illustration of the aforesaid in Table 2 are compared
the values of pKa of aminophosphine oxides and the
respective amine precursors.
We determined for the first time the ionization
constants of N,N’-bis-phosphorylated 1,6-diamino-
hexane XXIV. In this case the influence on the basicity
of the introduction of phosphinyl groups is clearly
seen: the change in pKa at the both stages of
dissociation occurs in the same range as in the case of
monobasic amines. Thus, to 1,6-hexamethylene-
diamine correspond the values of pKa1 = 10.06 and
pKa2 = 9.08; for its 1,6-bis(dioctylaminomethyl-
phosphinyl) derivative are obtained the values of
pKa1 = 5.90 and pKa2 = 5.42, i.e., the difference in the
acidity ΔpKa for two stages is respectively 4.16 and
3.66 pKa units.
The aminophosphoryl carriers synthesized by us we
investigated in the processes of the membrane
extraction of organic acids of the moderate strength
differing by the number of functional groups: acetic,
glutaric, tartaric and citric. The sequential growth of
the number of hydrophilic carboxy and hydroxy
groups in them should have strongly affected their
ability “to utilize” certain basic centers of carriers, and
also to form the H-bond complexes of different
strength with the molecules of water in the source
phase.
It is noteworthy that we failed to determine the
precise values of the pKa of bis-phosphorylated amines
XIV–XVI. Under the conditions of titration selected
by us the necessary portion of the protonated form of
these compounds was not reached. However, this fact
is completely understandable: if we proceed from the
assumption that the introduction of the second
methylenephosphoryl group contributes the same as
the mono-phosphorylation, then the pKa of bis-phos-
phorylated amines must have values less than 1.7.
The purposeful selection of the aminophosphoryl
carriers by structure we accomplished taking into
account that, as had been established earlier [21],
among the functionalized phosphoryl compounds
which contain hydroxy, alkoxy and amino groups
located in different position with respect to phosphorus
atom, the most effective membrane transfer of acids
was observed just in the case of amino derivatives: the
flow value of the transfer by aminophosphonates
considerably exceeded that of oxygen analogs.
Obviously the hydrogen binding of the transferred
substrate acid by nitrogen centers is much stronger
than by oxygen centers. Introduction into the molecule
of the carrier of the second phosphoryl group to the α-
position (compounds XII–XVI) or the γ-position
(compound XI) with respect to nitrogen atom not only
The fact of the low basicity of bis-phosphorylated
amines is very remarkable. We suggest that lipophilic
bisphosphorylated amines are of undoubted interest as
new extraction reagents, since a weak affinity to
proton must lead to an essential difference in the
behavior of these reagents at the extraction of metals
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SYNTHESIS OF NEW LIOPHILIC FUNCTIONALIZED AMINOMETHYLPHOSPHINE OXIDES
1843
Table 3. Values of flows (P) at the membrane transport of
acetic, glutaric, citric and tartaric acids. Concentration of
carrier in the membrane phase 0.1 М, concentration of
substrate in source phase 0.2 М. Error of measuring P ±
10%
changes (decreases) the electron density on the latter
[6], but also creates obvious steric hindrances for the
com-plexation, especially for the large molecules of
polybasic acids. Thus, we were able to estimate the
efficiency and the selectivity of membrane extraction
and the concentration of acid substrate taking com-
plementary pairs substrate–aminophosphoryl carrier.
P×106, mol m–2 min–1
Comp. no.
Acetic
Glutaric
Citric
Tartaric
As the membrane solvent we selected low polar
phenylcyclohexane, which excludes the possibility of
the specific solvation both of carriers and of the com-
plexes formed in the membrane phase.
170
100
73
79
2.0
3.0
0.3
260
6.0
0.3
330
250
100
15
19
0.06
−
I
−
IV
4.0
−
V
We repeatedly have indicated [8, 21] that in the
processes of the membrane transfer through the liquid
impregnated membranes the simple dependences
between the structure and the transport properties of
carriers usually cannot be found, since the efficiency
of the transfer depends both on the carrier binding with
the substrate and on the ease of the reextraction into
the receiving phase. Furthermore, in the case of
polyfunctional complexones of the type of the amino-
phosphoryl compounds under study, into the binding
with the transferred substrate can be involved at once
not all centers of coordination, for example, by steric
reasons. It is important also that the rate of transfer is
connected also with the the characteristics of the
medium viscosity of all phases that also cannot be
completely estimated.
200
190
170
79
13
95
−
0.06
2.0
0.6
1.0
11
35
34
1.0
18
15
3.0
11
2.0
1.0
−
VI
VIII
IX
−
X
420
610
410
240
460
500
500
710
150
78
23
60
62
XI
XII
XIII
XIV
XV
2.0
240
280
140
450
29
30
25
4.0
38
XVI
XVII
XVIII
XIX
XX
2.0
At the same time, analysis of the results of
determining the flow values of transfer of organic
acids by different aminophosphoryl compounds through
the liquid membranes listed in Table 3 makes it
possible to reveal some trends in the interrelation
between the structure of the partners interacting at the
complex formation and the efficiency of the transfer.
This interrelation is manifested distinctly at the
analysis of the transfer of monobasic acetic acid. The
comparison of flow values for phosphorylamines I–X
confirms the fact we have noted earlier [21] that the
center of the carrier protonation is the nitrogen atom,
while the phosphoryl oxygen atom is not involved into
the binding the substrate or little affects the transfer
efficiency. The phosphoryl carriers not containing
nitrogen atoms sharply increase their efficiency at the
transfer of monobasic acids upon the replacement of
electron-acceptor alkoxy substituents at phosphorus by
the donor alkyl groups. In this case the comparison of
the flow values of the transfer in the series of
phosphine oxides and phosphonate VI shows that the
replacement of donor alkyl groups in phosphine oxide
amines by the acceptor cyclohexyloxy substituents at
14
1.0
1.5
110
270
300
390
10
XXI
XXII
XXIII
XXIV
150
6.0
100
34
12
−
−
74
34
the phosphoryl center does not decrease, but on the
contrary, increases the flow intensity. Undouptedly,
together with the basicity of amino center, an
important role in the case of phosphonate VI belongs
to the high lipophilicity of the carrier caused by the
presence of two isooctyl groups at the nitrogen atom.
The transport properties of two aminophosphine
oxides I and VIII, phosphonate VI, diphosphine oxide
XV and phosphorylated γ-phosphonate XI we already
described in [13]. For the completeness of con-
sideration we use some data from that publication that
which in essence well agree with newly obtained data
for aminophosphoryl compounds lacking additional
centers of coordination. The majority of monophos-
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1844
CHERKASOV et al.
phorylated aminophosphine oxides I, IV, VII, and IX
possesses a moderate efficiency of the acetic acid
transfer, in the range of 100–200 P, and in these cases,
obviously, the solvate mechanism operates which
assumes the formation of the aminoacid N-complexes.
Falling out from this series of phosphine oxides of
compound X is due undoubtedly to the presence at the
phosphorus atom of two acceptor tolyl groups. As to
the low transport properties of secondary amine V, this
fact most likely is connected with the insufficient
lipophilicity of the carrier. Previously we showed
[1, 5] that the acceptable interphase distribution was
achieved at the presence in the molecule of
aminophosphoryl compound no less than 20 carbon
atoms.
hampers its complexing with the proton-donor
substrate. However, this carrier displays high activity
not only with respect to acetic acid, but also toward
other selected substrates. The possible reason for this
phenomenon can be the ability of hydroxyl to bind into
complex B the acetate anion “liberated” after the
protonation of nitrogen.
O
O
H
+N
P(C6H13)2
O
(C6H )
13 2P
C
O
CH3
−
H
O
B
In this connection a special interest presentes an
example of the phosphorylated aminoalcohol XVIII,
which demonstrates exclusively high transport activity.
On the basis of the above suggested model of
participation of a hydroxy group in “additional”
binding of the transferred acid substrate (acetic acid),
the structure appearing in this case can be represented
in the form H-bound complex C.
The sharp increase in the flow value of the acetic
acid transfer in the case of diphosphorylated amines
XII–XVII is natural to connect with “involvemnt” into
the complex formation with acetic acid also of other
centers of basicity: one or two phosphoryl oxygen
atoms. We initially expressed it as assumption [13],
but now it is confirmed by the experimental data
obtained in this study: diphosphine oxides XV and
XVI, phosphonatephosphine oxide XIV, and,
especially, “mixed” diphosphorylamine XII demonstrate
high transport efficiency with respect to acetic acid. In
this case the high result obtained with the latter
compound, as we assume, is caused by the optimum
combination of the basic properties of the carrier with
its hydrophilic–lipophilic balance.
O
H
+N
(C6H )
13 2P
C6H13
O
C
O
CH3
−
H
O
C
Thus, the presence of “additional” hydrophilic
function in the carrier capable of forming with the
molecule of substrate one or more additional hydrogen
bonds is favorable for the process of the membrane
transport of proton-donor substrate.
With respect to α,α-diphosphorylamines XII, XIV–
XVI it would be possible to use the model of the
tricentric hydrogen binding of hydrogen atom with
nitrogen and two oxygen atoms of phosphoryl groups
(complex A). However, this assumption requires
serious experimental testing, for example, at the level
of X-ray diffraction analysis on the specially
synthesized models that we intend to make in future.
We attempted to verify this assumption by the
example of the phosphorylated amino acids XIX–XXI.
It turned out that in this case the flow values at the
transfer of acetic acid are quite moderate and are
comparable with those of α-aminophosphine oxides I,
IV, V, and IX. It seems that the additional proton-
donor carboxylic groups do not participate in the
process of binding the substrate. This is possible only
in two cases. First, the acidic groups are not
dissociated under the conditions of the interphase
transfer, and the center of binding is the tertiary
nitrogen atom, a highly improbable version. Second,
phosphine oxides XIX–XXI like any amino acids are
zwitter-ions due to “internal” protonation of nitrogen
by the carboxyl group. In this case the carboxylate
anion and/or phosphoryl group should behave as the
R
H
O
O
P
P
N
A
Noteworthy is a sufficiently high transport activity
of diphosphine oxide XIII containing hydroxyethyl
group at the nitrogen atom. It is expectable owing to
the increased hydrophilic nature of this reagent that
leads to its retention in the source phase or, at least,
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SYNTHESIS OF NEW LIOPHILIC FUNCTIONALIZED AMINOMETHYLPHOSPHINE OXIDES
1845
center of coordination with the acid substrate. As we
have established earlier [21], these functional groups
are less effective in the processes of the membrane
transport of acids than the amino centers of carriers. It
is very significant that the ester XVII incapable of various
prototropic processes shows high membrane transport
activity with respect to acetic acid as compared with
the activity of diphosphine oxides XV and XVI.
obvious: sterically completely hindered α,α-diphos-
phinylamines XV and XVI due obviously to screening
of the nitrogen center are less accessible for the bulky
glutaric acid than α,γ-analog XI. The reason for the
low performance at the transfer of glutaric acid by
phosphine oxides II and III and especially by phos-
phonate VI can be the unfavorable hydrophilic–lipo-
philic balance of the carrier (previously such difference
at the change in the length of hydrocarbon groups at
the phosphorus atom has been observed at the study of
membrane transport with the participation of phospho-
rylated azapodands [3]). Another possible cause of the
observed phenomenon is the presence of the second
hydrophilic carboxy group not connected with the carrier,
which retains substrate in the source phase because of
the strong hydrogen bonds with the medium. However,
the absence of transfer via the formation of complex with
phosphonate VI can be due to the specific properties of
the complex, for example, to poor solubility in the
membrane organic phase. The anomalously high index
of transfer characteristic of phosphorylated ethanol-
amine XVIII appeared also in the case of glutaric acid.
The most plausible explanation is the formation of a
complex of the same type as that formed by acetic
acid, while the “extra” carboxylic group is connected
by hydrogen bond with the phosphoryl oxygen. However,
this hypothesis needs experimental confirmation.
Diphosphorylated diamines XXIII and XXIV
exceed in the effeiciency of the transfer of acetic acid
their “monoamine” analogs. Possibly in these cases
each amino group operates as an independent center of
coordination, and the highest activity of 1,6-
diaminohexene derivative XXIV is connected with the
comparatively favorable steric conditions for the
formation of N-complexes with all nitrogen atoms,
which are sufficiently “distant” from each other.
The interrelation “structure–efficiency of transfer”
seems more ambiguous in the case of dicarboxylic
glutaric acid. Although in this case the tendency is
observed of an increase in the transfer by the
diphosphoryl carriers, however it is not so clearly
expressed as for the monobasic acid substrate. The
high index for phosphine oxide VIII can be understood
as the participation of both carboxy groups of acid in
the protonation of two basic centers of the phos-
phorylated amine, as the relative steric accessibility of
the second atom of nitrogen, and as the suitable
hydrophilic–lipophilic balance. Approximately the
same factors can determine a comparatively high rate
of transfer of this dicarboxylic acid by diphos-
phorylated amines XI, XII, XV, and XVI.
The relatively low flow values of the transfer of
glutaric acid by diaminodiphosphine oxides XXIII and
XXIV can be understood only by eclipsing of nitrogen
atoms by the large dialkylphosphinyl groups, which
hamper the complexing with the large molecule of
dicarboxylic acid. At the same time quite accessible
nitrogen atom of pyridine fragment in phosphine oxide
XXII makes this carrier completely suitable for the
transport of dibasic acids.
A possibility of both basic centers of α-amino-
phosphonates to bind hydrogen simultaneously was
previously shown in the study of the membrane
transport of α-hydroxy acids [22–23]. The X-ray
structure of the complex reveals the protonation of
amino center by the carboxy group while the phos-
phoryl oxygen atom is connected by a hydrogen bond
with the hydroxyl proton of the transferred acid. It is
interesting that the hydroxy proton of substrate is
connected also with one of the atoms of acylate anion,
thus forming a tricentric hydrogen bond; we noted
above a possibility of existence of the latter.
The effect of “additional” hydrophilic group which
we had observed earlier for the transfer of dicarboxylic
acids and hydroxy acids by the functionalized
phosphoryl carriers [21] was fully found also in this
study. The low flow values of transfer of di- and
tricarboxylic hydroxy acids, tartaric and citric,
obviously is connected just with the high hydrophilic
nature of the N-complexes of phosphorylated amines
with these substrate: the number of basic centers is
insufficient for binding all proton-donor functional
groups of these substrates. The free extra hydroxy and
carboxylic groups enter into the hydrogen bonding
with the molecules of water and therefore are retained
in the source phase.
In the formation of complexes by diphosphorylated
amines with the acid substrate an important role,
besides the basicity of the centers of protonation,
obviously plays the steric effect. In this sense the
essential difference in the efficiency of the transfer is
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1846
CHERKASOV et al.
Thus, the results of this work show that the
when necessary were purified additionally employing
known procedures. Primary and secondary amines
produced by Acros Organics were used. Toluene-
sulfonic acid is of “chemically pure” grade. Other
substances if necessary were synthesized from the
commercially accessible reagents employing standard
procedures.
performance of the membrane transport of the
substrate of different nature is provided only at the
complementary cooperation of carrier with the trans-
ferred substance. Thus, at the ion transfer of metals by
phosphorylated azapodands [11] or at the use of
aminophosphoryl compounds in the ion-selective elec-
trodes [9] an important role belongs to the cor-
respondence of the size of ion and potential pseudo-
cavity formed by the podand. In the processes of the
membrane transport of acidic substrate the accounting
is important for the acid–base interactions of proton
donor with the potential electron-donor centers of the
complex-forming agent, and for the presence or
absence of “additional” hydrophilic groups in the
substrate and the carrier. Obviously, the speciic feature
of hydrophilic-lipophilic balance both in the carrier
and in the complex formed by it should be taken into
consideration, although the exact estimation of this
factor is difficult. This fully corresponds also to the
estimation of the steric factors, essential at the
formation of the complexes transferred into the
membrane phase. Nevertheless, the laws governing the
change in the transport properties of carriers in the
dependence on their structure and nature of the
transferred substrate that we revealed make it possible
to a certain approximation to optimize the processes of
membrane transport by the selection of complementary
substrate–carrier pairs.
At the potentiometric titration of aminophosphoryl
compounds were used ES-1060 glass electrode, ESr-
1010 silver chloride electrode filled with 3 M solution
of KCl, universal ionomer I-160MI, and a thermostat
U15 MLW. For the preparation of solutions was used
2-propanol of “chemically pure” grade, potassium
chloride of “extra pure” grade, and bidistilled water.
Processing of analytical data was accomplished on the
computer using original software on the base of
VisualBasic compiler.
The research of membrane transport properties of
aminophosphoryl compounds was carried out on the
installation we described in [24]. As a hydrophobic
matrix for the impregnated membranes were used the
porous filters “Vladipor” MFFK-4, with the size of
pores 0.6 μm that were Teflon matrix on the polyester
support. The acid–base titration was performed with
the use of a 10 ml burette, a change in pH was fixed by
a laboratory ionomer I-30 measuring the potential of
glass electrode relative to the silver chloride reference
electrode.
EXPERIMENTAL
General procedure of the synthesis of amino-
methylphosphoryl compounds in three-component
system of hydrophosphoryl compound, formal-
dehyde, and amine. In a round-bottom three-neck
100 ml flask equipped with a mechanic stirrer, a Dean–
Stark trap, and a reflux condenser were mixed
50 mmol of phosphoryl compound, 52.5 mmol of
paraform, 52.5 mmol of amine, 35 ml of anhydrous
nonpolar high-boiling solvent (benzene, toluene, o-
xylene), and 100 mg of p-toluenesulfonic acid. The
obtained mixture was refluxed with stirring till
complete liberation of water into the trap. The course
of reaction was monitored by measuring the volume of
water in the Dean–Stark trap, by the method of TLC,
and also by 31P NMR spectra of the sampes. At the end
of the reaction into the solution ~500 mg of K2CO3
was added, and the mixture was refluxed for 10 min
for the removal of catalyst. The mixture was then
cooled, washed with water (3×5 ml), and dried over
anhydrous MgSO4. The filtrate was evaporated in a
vacuum on the rotary evaporator. The obtained
The 31P NMR spectra were registered on a Varian
Unity instrument with the operating frequency 300
MHz (external reference 85% phosphoric acid) in the
1
solution of deuterochloroform; the H NMR spectra
were taken on Varian Unity instruments with operating
frequencies 300 and 400 MHz (internal reference
TMS) from the condensed phase or solution in
benzene. The IR spectra were registered on a Specord-
M80 spectrometer.
The completion of the reactions was monitored by
the volume of isolated water in Dean–Stark trap as
compared with the calculated volume of water (in the
case of nonpolar solvent) and by the method of thin-
layer chromatography with references on silica gel
(Silufol). The mobile phase is a mixture of chloroform
and acetone (3: 1); development by treatment with
iodine vapor and then by distilled water.
For the syntheses were used the solvents of the
“analytically pure” and “chemically pure” grade which
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SYNTHESIS OF NEW LIOPHILIC FUNCTIONALIZED AMINOMETHYLPHOSPHINE OXIDES
1847
substances were oily or crystalline compounds; the
yields of aminophosphoryl compounds are 60–95%.
Oxalic derivative of phosphine oxide IX. mp =
145°C, yield 90%. Found, %: C 63.42, N 2.99, H
11.45. C25H50NO5P. Calculated, %: C 63.13, N 2.94, H
10.60.
Oily residue was treated with a calculated amount
of oxalic acid in diethyl ether. The separated white
crystalline precipitate was recrystallized from acetone,
treated with aqueous solution of alkali to neutral
reaction, and the target aminophosphoryl compound
was extracted with toluene, the extract was dried over
anhydrous magnesium sulfate, then the solvent was
removed in a vacuum. The methods of synthesis and
the characteristic of compounds I, VI, VII, XI and XV
were described earlier [13].
Di-p-tolyl-N-octylaminomethylphosphine oxide
(X). nD20 = 1.4749, yield 80%, Rf 0.4. Found, %: N
3.72, P 7.94. C23H34NOP. Calculated, %: N, 3.77; P,
8.34.; IR spectrum, ν, cm–1: 1121 (P=O); 31P NMR
1
spectrum: 27 ppm. H NMR spectrum, ppm: 7.60 m
2
(CH)4, 7.25 m (CH)4, 3.46 d (CH2, JP–H = 7.2 Hz),
3
3.02 t (CH2, JC–H = 6.9 Hz), 1.46 br.s (CH3), 1.25 m
(CH2)6, 0.94 m (CH3)2.
Oxalic derivative of phosphine oxide X. mp =
153°C, yield 86%. Found, %: C 65.04, N 3.11, H 7.82
C25H36NO5P. Calculated, %: C 65.06, N 3.03, H 7.86.
Dihexyl-N-cyclohexylaminomethylphosphine oxide
(II). nD20 = 1.4870, yield 98%, Rf 0.58. Found, %: N
4.73, P 8.59 C19H40N2OP. Calculated, %: N 4.28, P
9.46; P NMR spectrum: 45 ppm. H NMR spectrum,
ppm: 2.84 d (CH2, 2JP–H = 6 Hz), 2.33 br.s (CH), 1.78–
0.83 m [(CH3)2, (CH2)15, NH].
31
1
N-[(Dibutoxyphosphoryl)methyl]-N-[(dioctylphos-
phinyl)methyl]butylamine (XII). Yield 60%. 31P
NMR spectrum: (C6H6, 300 Hz); δ, ppm: 43; 26.
Dihexyl-N,N-dioctylaminomethylphosphine oxide
(III). nD20 = 1.4652, yield 80%, Rf 0.51. IR spectrum, ν,
cm–1: 1158 (P=O); 31P NMR spectrum: 47 ppm.
Dihexyl-N-2-hydroxyethyl-N-(dihexylphosphinyl-
methyl)phosphine oxide (XIII). mp = 89°C, yield
45%, Rf 0.15. Found, %: N 2.61, H 12.17, C 62.86.
C28H61NO3P2·H2O. Calculated, %: N 2.60, H 11.86, C
62.31. IR spectrum, ν, cm–1: 1145 (P=O), 3240 (OH);
31P NMR spectrum: 46 ppm. 1H NMR spectrum, ppm:
Dihexyl-N,N-dibutylaminomethylphosphine oxide
(IV). nD20 = 1.4648, yield 85%, Rf 0.53 .Found, %: N
1
4.46. C2 H46NOP. Calculated, %: N 3.90; IR spectrum,
1
ν, cm–1 : 1161 (P=O). 31P NMR spectrum: 47 ppm. H
2
3
3.09 d [(CH2)2, JP–H = 4.8 Hz], 3.01 t (CH2, JC–H
4.8 Hz), 3.66 t (CH2, JC–H = 4.8 Hz), 2.67 br.s (OH),
=
2
3
NMR spectrum, ppm: 2.69 d (CH2, JP–H = 7.2 Hz),
3
2.49 t [(CH2)2, JC–H = 6.6 Hz], 1.67–0.87 m [(CH3)4,
1.8–1.1 m [(CH3)4, (CH2)20].
(CH2)14].
Dibutyl N-octyl-N-(dibutyloxyphosphinylmethyl)
phosphonate (XIV). nD20 = 1.4520, yield 90%, Rf 0.52.
Found, %: N 2.78. C26H57NO6P2. Calculated, %: N
2.59. IR spectrum, ν, cm–1: 1027 (P=O); 31P NMR
spectrum: (C6H6, 300 Hz); 25 ppm.
Dihexyl-N-butylaminomethylphosphine oxide (V).
nD20 = 1.4710, yield 81%, Rf 0.57. Found, %: N 4.62
C17H38NOP. Calculated, %: N, 4.62. IR spectrum, ν,
cm–1: 1144 (P=O). 31P NMR spectrum: 44 ppm. H
1
2
NMR spectrum ppm: 2.85 d (CH2, JP–H = 8.7 Hz),
2.62 t (CH2, JC–H = 5.7 Hz), 1.67–0.81 m [(CH3)3,
(CH2)12, NH].
Dihexyl-N-octyl-N-(di-p-tolylphosphinylmethyl)
phosphine oxide (XVI). nD20 = 1.5190, yield 70%, Rf
0.55. Found, %: N 2.91. C36H61NO2P2. Calculated, %:
N 2.33. IR spectrum, ν, cm–1: 1121 (P=O), 1179
3
Dioctyl-N-butylaminomethylphosphine oxide (VII).
nD20 = 1.4719, yield 98%, Rf 0.57. Found, %: N 4.40
C21H46NOP. Calculated, %: N 3.92; 31P NMR spec-
1
(P=O). 31P NMR spectrum: 45, 27 ppm. H NMR
spectrum, ppm: 7.74 m (CH)4, 7.38 m (CH)4, 3.59 d
(CH2, 2JP–H = 5.4 Hz), 3.05 d (CH2, 2JP–H = 6 Hz), 2.92
t (CH2, 3JC–H = 4.2 Hz), 2.38–0.93 m [(CH3)5,(CH2)16].
1
trum: 45 ppm; H NMR spectrum, ppm: 2.86 d (CH2,
2JP–H = 6 Hz), 2.63 t (CH2, 3JC–H = 7.5 Hz), 1.7–0.89 m
[(CH3)3, (CH2)17, NH].
Dihexyl-N-butyl-N-ethoxycarbonylaminomethyl-
phosphine oxide (XVII). nD20 = 1.4652, yield 95%, Rf
0.4. Found, %: N 3.71, P 7.27. C21H44NO3P.
Calculated, %: N 3.60, P 7.95. IR spectrum, ν, cm–1:
Dioctyl-N-cyclohexylaminomethylphosphine oxide
(IX). nD20 = 1.4760, yield 82%, Rf 0.61. Found, %: N
3.48, P 7.67. C23H48NOP. Calculated, %: N 3.63; P,
8.03. IR spectrum, ν, cm–1: 1147 (P=O); 31P NMR
1
1156 (P=O). 31P NMR spectrum: 49 ppm. H NMR
3
1
spectrum (CDCl3, 300 Hz); ppm: 4.11 q (CH2 JC–H
=
spectrum: 43 ppm. H NMR spectrum ppm: 2.84 d
[(CH2) JP–H = 8.1 Hz], 1.78–0.80 m [(CH3)2, (CH2)19,
6 Hz), 3.39 s (CH2), 2.99 d (CH2, 2JP–H = 6 Hz), 2.68 t
(CH2, 3JC–H = 6 Hz), 1.69–0.85 m [(CH3)4, (CH2)12].
2
NH, CH].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009

1848
CHERKASOV et al.
Found, %: N 4.03, C 69.94, H 13.28. C40H86N2O2P2.
Calculated, %: N 4.07, C 69.72, H 12.58. IR spectrum,
ν, cm–1: 1148 (P=O), 3275 (NH). 31P NMR spectrum:
Didecyl-N-hexyl-N-(2-hydroxyethyl)aminomethyl-
phosphine oxide (XVIII). nD20 = 1.4728, yield 77%, Rf
0.66. Found, %: N 3.71, P 7.27 C21H44NO3P.
Calculated, %: N 3.60, P 7.95. IR spectrum, ν, cm–1:
1138 (P=O), 3300 (OH). 31P NMR spectrum: (C6H6,
300 Hz); 47 ppm. 1H NMR spectrum (CDCl3, 300 Hz);
43 ppm. 1H NMR spectrum, ppm: 2.88 d [(CH2)2, 2JP–H
=
3
5.4 Hz], 2.65 t [(CH2)2, JC–H = 6.9 Hz], 1.8–0.8 m
[(CH3)4, (CH2)32, (NH)2].
ppm: 3.61 t (CH2, 3JC–H = 4.8 Hz), 2.21 d (CH2, 2JP–H
4.2 Hz), 2.73 t (CH2, JC–H = 4.8 Hz), 2.58 t (CH2,
=
3
ACKNOWLEDGMENTS
3JC–H = 7.2 Hz), 1.1–0.8 m [(CH3)3, (CH2)23].
This work was financially supported by the Russian
Foundation for basic Research, grant 07-03-00306.
Didecyl-N-butyl-N-carboxymethylaminomethyl-
phosphine oxide (XIX). mp = 50°C, yield 90%, Rf
0.47. Found, %: %: N 3.79, P 7.73, C 62.44, H 11.80.
C19H40NO3P. Calculated, %: N 3.87, P 8.57, C 63.13,
REFERENCES
1
H 11.15. 31P NMR spectrum: 53 ppm. H NMR spec-
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R.A,
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G.Kh.,
and
2
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2.73 t (CH2, 3JC–H = 6 Hz), 1.75–0.85 m [(CH3)3, (CH2)11].
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Oxalic derivative of phosphine oxide XIX. mp =
50°C, yield 90%, Rf 0.66. Found, %: C 63.78, N 2.48,
H 11.43. C3 H64NO6P. Calculated, %: C 64.44, N 2.48,
1
H 11.19.
Dioctyl-N-butyl-N-carboxymethylaminomethyl-
phosphine oxide (XX). mp = 65°C, yield 90%, Rf
1
0.51. 31P NMR spectrum: (C6H6, 300 Hz); 53 ppm. H
NMR spectrum, ppm: 3.48 s (CH2), 3.06 d (CH2, 2JP–H
=
6 Hz), 2.73 t (CH2, 3JC–H = 6 Hz), 1.75–0.85 m [(CH3)3,
(CH2)11].
Dioctyl-N-butyl-N-carboxymethylaminomethyl-
phosphine oxide (XXI). mp = 84°C, yield 90%, Rf
0.46. Found, %: N 2.94. C23H48NO3P. Calculated, %:
N 3.35. IR spectrum, ν, cm–1: 1027 (P=O). 31P NMR
1
spectrum: 53 ppm. H NMR spectrum, ppm: 3.71 s
(CH2), 3.28 d (CH2, 2JP–H = 6 Hz), 2.90 t (CH2, 3JC–H
=
6 Hz), 1.91–0.97 m [(CH3)3, (CH2)17] .
Didecyl-β-(2-piridyl)aminophosphine oxide (XXII).
Yield 90%. 31P NMR spectrum: (C6H6, 300 Hz);
30.7 ppm.
Oxalic derivative of phosphine oxide XXII. Yield
80%. Found, %: C 63.85. C28H51N2O5P. Calculated, %:
C 63.56.
N,N-Bis(didecylphosphinylmethyl)tetramethylene-
diamine (XXIII). mp = 80°C, yield 75%, Rf 0.3.
Found, %: C 72.03. C46H98N2O2P2. Calculated, %: C
71.45. IR spectrum, ν, cm–1: 1150 (P=O), 3280 (NH).
31P NMR spectrum: 46 ppm. 1H NMR spectrum, ppm:
2.87 d [(CH2)2, 2JP–H = 7.8 Hz], 2.66 t [(CH2)2, 3JC–H
=
6 Hz], 1.8–0.8 m [(CH3)4, (CH2)32, (NH)2].
13. Cherkasov, R.A., Talan, A.S., Tarasov, A.V., and
Garifzyanov., A.R., Zh. Obshch. Khim., 2008, vol. 78,
no. 7, p. 1093.
N,N-Bis(didecylphosphinylmethyl)hexamethylene-
diamine (XXIV). mp = 82°C, yield 85%, Rf 0.15.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009

SYNTHESIS OF NEW LIOPHILIC FUNCTIONALIZED AMINOMETHYLPHOSPHINE OXIDES
1849
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