Synthesis and ionophoric properties of α,ω-diphosphorylated aza podands: II. Kabachnik-fields reaction as a method for design of α,ω-diphosphorylated aza podands and their use for determination of metal ions

Article abstract of DOI:10.1007/s11176-005-0201-6

Methods of the design of podands with α-aminomethylphosphine oxide terminal groups with the purpose of investigation of the ionophoric properties of the podands and their use as components of ion-selective electrodes are analyzed. The most convenient procedure is a one-pot synthesis based on the Kabachnik-Fields reaction in a system comprising a dialkyl(aryl)phosphinous acid, formaldehyde, and a diamine. An alternative procedure is two-stage and involves the reaction of a primary amine with a phosphinous acid and formaldehyde to form an α-aminomethyldialkyl(aryl)phosphine oxide in the first stage and cross-linking of two molecules of this compound via reaction with a dihalooligoether of the corresponding length in the second. Advantages and disadvantages of both procedures are considered. Electrode-active properties of the prepared aza podands are studied to show that ion-selective electrodes on their basis can be used for selective determination of low concentrations of alkali and alkaline-earth metal ions. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11176-005-0201-6

Russian Journal of General Chemistry, Vol. 75, No. 2, 2005, pp. 217 224. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 2, 2005,
pp. 244 252.
Original Russian Text Copyright
2005 by Garifzyanov, Vasil’ev, Cherkasov.
Synthesis and Ionophoric Properties
of , -Diphosphorylated Aza Podands:
II.1 Kabachnik Fields Reaction as a Method for Design
of , -Diphosphorylated Aza Podands
and Their Use for Determination of Metal Ions
A. R. Garifzyanov, R. I. Vasil’ev, and R. A. Cherkasov
Kazan State University, Kazan, Tatarstan, Russia
Received August 28, 2000
Abstract Methods of the design of podands with -aminomethylphosphine oxide terminal groups with the
purpose of investigation of the ionophoric properties of the podands and their use as components of ion-selec-
tive electrodes are analyzed. The most convenient procedure is a one-pot synthesis based on the Kabachnik
Fields reaction in a system comprising a dialkyl(aryl)phosphinous acid, formaldehyde, and a diamine. An
alternative procedure is two-stage and involves the reaction of a primary amine with a phosphinous acid and
formaldehyde to form an -aminomethyldialkyl(aryl)phosphine oxide in the first stage and cross-linking of
two molecules of this compound via reaction with a dihalooligoether of the corresponding length in the second.
Advantages and disadvantages of both procedures are considered. Electrode-active properties of the prepared
aza podands are studied to show that ion-selective electrodes on their basis can be used for selective determina-
tion of low concentrations of alkali and alkaline-earth metal ions.
One of the most promising fields in the chemistry
of host guest complexes is design of polyfunctional
host molecules with preset properties, capable of ef-
fectively binding inorganic and organic molecules.
Various complex-forming agents that can play the role
of a host are nowadays used in ion-selective elec-
trodes, membrane transport, and as biologically active
compounds, catalysts, etc. Podands with donor
terminal groups hold much promise in this respect [2].
Of them the most extensively studied are oligoethers
with amino and amido terminal groups [3], that have
found wide application as components of ion-selective
electrodes for metal cations [4, 5]. Considerable recent
attention has been attracted to podands with phos-
phine oxide and phosphonate terminal groups, as
potent complex-forming agents for alkali metal
cations and effective neutral carriers and extractants
for rare-earth metals [4 9]. The available published
data on the complex-forming ability of aminophos-
phonates and aminophosphine oxides suggest that
these compounds, too, may serve as effective reagents
for extraction and separation of metal ions [9, 10].
and properties of podands containing -aminoalkyl-
phosphoryl terminal groups is scarce. We set our-
selves the task to develop procedures for preparing
such structure with the aim to study their ionophoric
properties and utility as components of ion-selective
electrodes. It might be expected that introduction of
nitrogen atoms in phosphorylated podands would
significantly affect their extractive, transporting, and
ionophoric properties and endow the organophos-
phorus compounds with features inherent in mono-
functional aminophosphoryl carriers. These expecta-
tions were based on the structural similarity of phos-
phorylated aza podands having two -aminomethyl-
phosphine oxide terminal groups to macrocyclic
ligands, such as crown ethers or cryptands, on the one
side, and four-coordinate phosphorus compounds,
aminophosphonates and phosphine oxides on the other;
eventually, this would predetermine specific complex-
forming properties of such podands.
Analysis of published data on the synthesis of
phosphorylated compounds, as well as podands
having terminal nitrogen-containing functional groups
enabled us to outline a number of possible ways to
constructing the target compounds. One of them
might include the reduction of the nitro or nitroso in-
corporates in the structure of podands, like that
At the same time, the information on the synthesis
1
For communication I, see [1].
1070-3632/05/7502-0217 2005 Pleiades Publishing, Inc.

218
GARIFZYANOV et al.
described in [12]. However, this protocol seemed un-
likely to hold promise, because compounds containing
phosphoryl, nitro, and nitroso groups in one molecule
are usually synthesized by multistage and, therefore,
practically unfeasible procedures. Moreover, the reduc-
tion of the nitro and nitroso groups, which in the
frames of this strategy would lead to amino groups,
might touch the phosphoryl centers. For the above
reasons, we ruled out this synthetic approach to
phosphorylated aza podands.
sed on the creation of the -aminomethylphosphoryl
skeleton P(O)C N by means of the Kabachnik Fields
reaction in a three-component system comprising a
hydrophosphoryl and a carbonyl compounds, and an
amine. One of the participants of this process might
be alkanolamine I. This compound could be converted
into hydroxyl-substituted aminophosphoryl compound
II that is easy to covert into alcoholate III. Sub-
sequent reaction of the latter with , -dihaloethers or
other bifunctional compounds with easily leaving
groups, such as tosyl, would provide target aza
podand IV as the final product [Scheme (1)].
More attractive seemed the synthetic strategy ba-
Scheme 1.
R2PCH2NCH2CH2OH
Na
ether
R2PHO + CH2O + R NHCH2CH2OH
R2PCH2NCH2CH2ONa
H2O
R
O
R
O
I
II
III
R
R
O
2III + X
X
NCH2PR2
O
R2PCH2N
O
O
O
O
This strategy was subjected to experimental testing.
As the phosphorus-containing components we used
N-( -hydroxyethyl)- -aminomethylphosphine oxide
derivatives prepared by means of the Kabachnik
Fields reaction from dialkyl- or diarylphosphinous
acids, Paraform, and secondary amines with a -hydr-
oxyethyl substituent I. Aminomethylphosphorylated
alcohol II prepared in this manner was treated with
metallic sodium in ether to obtain sodium derivative
III whose suspension was treated with the correspond-
ing , -dihalooligoether.
functional version of a classical Kabachnik Fields
reaction, was found to be a more successful approach
[Scheme (2)].
Scheme 2.
O
R PHO + CH O +
O
NHBu
BuNH
2
2
IV
H2O
Bu
Bu
R2PCH2N
O
O
O
NCH2PR2
However, this method did not lead to the desired
result. After removal of sodium chloride, in the 31P
NMR spectrum of the reaction mixture we observed
several groups of signals presumably belonging to the
phosphorus atoms in phosphine oxide and phosphine
structures. This result is probably associated with the
fact that the described reaction pathway was com-
plicated by the redox processes yielding phosphines
and phosphonium salts, that develop on treatment of
N-alkyl-N-(hydroxyethyl)aminomethylphosphine
oxides with sodium. Our attempts to carry out the
analogous reaction with ditosyl derivatives of oligo-
ethers failed. Hence, this method, too, proved to be
unsuitable for our purposes.
O
VI IX
R = pentyl (V), p-Tol (VII), octyl (VIII), decyl (IX).
This process was carried out with aliphatic (di-
amyl-, dioctyl-, didecyl-) and an aromatic (di-p-tolyl-)
phosphinous acids. N,N -Dibutyl-1,10 diaza-4,7-di-
oxadecane IV was chosen as the bifunctional amine.
The phosphine oxide Paraform diamine molar ratio
was 2:2:1. The reaction was carried out in boiling
benzene or toluene, using a Dean Stark trap. The re-
action progress was controlled by the amount of water,
as well as by means of TLC and 31P NMR spec-
troscopy.
The Kabachnik Fields reaction in a system com-
prising a hydrophosphoryl compound, formaldehyde,
and , -bis(alkylamino)oligoether IV, i.e. the bi-
After the reaction had been complete, the solvent
was removed in a vacuum, and the residue was dried
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SYNTHESIS AND IONOPHORIC PROPERTIES OF , -DIPHOSPHORYLATED AZA PODANDS: II. 219
Table 1. Characteristics of phosphorylated aza podands of the general formula
O
O
R2P CH2 N X N CH2 PR2
R
R
Comp.
no.
IR spectrum,
(P=O), cm
R
R
X
n2D0
Rf
Yield, %
, ppm
1
VI
Pentyl
p-Tol
Octyl
Decyl
Octyl
Decyl
Bu
TEGa
TEG
TEG
TEG
(CH2)2
N(CH2CH2)2N
1.4763
0.407
0.45
0.588
0.484
0.35
64
68 74
64
76
99 (73)
67
1165
1190
1150
1140
1140
1160
46
b
VII
VIII
IX
X
XI
Bu
Bu
Bu
Bu
24.7
44.53
43.2
49
1.4735
b
1.472
c
0.297
51
Table 1. (Contd.)
Found, %
Calculated, %
H
Comp. no.
Formula
C
H
P
C
P
VI
65.1
11.75
9.21
12.3
12.5
12.63
12.47
9.3
6.66
7.5
6.57
8.33
8.05
C36H78N2O4P2
C44H62N2O4P2
C48H102N2O4P2
C56H118N2O4P2
C44H94N2O2P2
C46H96N2O2P2
67.55
73.84
70.1
70.9
71.12
71.83
12.41
8.76
11.76
12.54
12.52
12.31
9.1
6.96
7.4
6.43
8.43
7.93
VII
VIII
IX
X
XI
73.74
69.23
71.19
70.97
71.69
a
b
c
TEG = CH CH OCH CH OCH CH
3
Tar.
Solid.
2
2
2
2
2
1
to constant weight and subjected to column chromato-
graphy on silica gel. Characteristics of products VI
IX are listed in Table 1.
In H NMR spectra of the phosphorylated 2,11-di-
aza-5,8-dioxadodecanone with tolyl substituents on
phosphorus (compound VII) there are a doublet of
doublets at 7.86 and 7.46 ppm, characteristic of aro-
matic systems, and a well-defined singlet at 2.6 ppm
from the p-methyl substituents of the tolyl groups on
phosphorus. The oxyethylene chain is identified by a
set of signals: The singlet at 3.63 ppm (4H) belongs to
protons of the symmetrical O CH2 CH2 O system of
the central ethylenedioxy fragment, the -methylene
P CH2 N group gives a doublet at 3.61 ppm (4H,
2JPH 15.3 Hz); and the N CH2CH2 O fragment gives
two well-defined signals: a triplet of the OCH2 group
Podands VI IX are viscous liquids readily soluble
in most organic solvents. Their purity was controlled
by TLC and elemental analysis, and the structure was
assessed by IR and NMR spectroscopy. The IR spec-
tra contain a characteristic sharp peak at 1140
1
1190 cm due to P=O stretching vibrations. Stretch-
ing vibrations of C O bonds appear in the range 1050
1
1100 cm , and symmetric and antisymmetric vibra-
tions of CH2 and CH3 groups, as characteristic multi-
1
plets at 3050 3100 cm . Aromatic aza podands VII
3
at 3.62 ppm (4H, JHH 5.9 Hz) and a triplet of the
is additionally identified by the characteristic bands at
3
1
N CH2 group at 2.96 ppm (4H, JHH 5.6 Hz). Protons
750 805 cm , belonging to out-of-plane deformation
1
of the butyl group attached to nitrogen appear as a
well-resolved group of signals in the range 1.02
2.84 ppm, characteristic of alkyl protons. Regretfully,
vibrations of the aromatic ring and at 1600 cm ,
belonging to double bonds of the tolyl group.
The 31P NMR spectra of the aliphatic phosphine
oxides all contain a singlet signal at 42 51 ppm and
those of the aromatic phosphine oxides, a signal at
25 ppm.
1
the H NMR spectra of aza podands with alkyl substi-
tuents on phosphorus proved to be poorly informative.
The latter synthetic approach was applied to
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220
GARIFZYANOV et al.
success to prepare bis(aminoalkyl)phosphine oxides
containing bridging ethylenediamine and piperazine
fragments (compounds X and XI, respectively).
Characteristics of these products are listed in Table 1.
Compound X is liquid, and it was purified by column
chromatography. Compound XI crystallizes as white
needles and was purified by crystallization from
hexane.
mentioned. First of all this is the limited possibility
of varying of the bridging polyether fragment in
podands (no more than two oxyethylene units can be
introduced). Furthermore, we came up against signi-
ficant difficulties in attempted synthesis of aza
podands with more lipophilic substituents on nitrogen,
since diaminooligoethers with long hydrocarbon
chains were hard to prepare pure. The example of
diaminophosphine oxide VII was used to show that
there is one more successful synthetic approach to
phosphorylated aza podands. By means of the Ka-
bachnik Fields reaction we prepared -aminophos-
phine oxide XII which was involved in reaction with
1,8-dibromo-4,7-dioxaoctane in the presence of
anhydrous potassium carbonate in DMF (Scheme 3).
The developed one-stage synthesis of bis( -amino-
methyl)phosphorylated ligands VI XI offers some
undoubted advantages. The target compounds are
formed in high or nearly quantitative yields. The re-
action proceeds under mild conditions and its progress
is controlled by simple methods.
Disadvantages of this method should also be
Scheme 3.
O
R
R2PHO + CH2O + R NH2
R2PCH2NH
H2O
V
R
R
O
O
Br
R2PCH2N
O
2V + Br
O
NCH2PR2
O
K2CO3, DMF
KBr
O
VII
R = p-Tol, R = Bu.
Spectral characteristics (31P NMR and IR) of the
samples of phosphorylated aza podand VII, obtained
by both the above-described methods are completely
identical. Our opinion is that the latter method is the
most promising. In this case, organic radicals of any
desired structure can be easily introduced to the phos-
phorus and nitrogen atoms of the aminophosphine
oxides prepared by the Kabachnik Fields reaction.
This type compounds are easily purified by usual
methods. Moreover, the dibromooligoethers used in
this procedure are comparatively available and can be
purified by vacuum distillation.
compound with a carbonyl compound and a primary
amine, followed by cross-linking of two molecules of
the phosphorylated secondary amine with a dihalo-
oligoether of corresponding length. Though these
procedures both are rather facile and practically
feasible, each of them has its merits and faults. The
choice of a suitable one depends on the desired hydro-
phobic hydrophilic balance or lipophilic character-
istics of the target podand. Undoubtedly, the desired
dimensions of the potential pseudocavity and number
of potential coordination centers should be taken into
account. Using the devised procedures we carried out
the first synthesis of new podands with -aminophos-
phoryl terminal groups, which allowed as to explore
their use as electrode-active components of ion-selec-
tive electrodes for chemical analysis.
Hence, we have developed two relatively facile and
convenient procedures for preparing phosphorylated
podands, based on the Kabachnik Fields reaction. The
first of them is a one-pot synthesis in a three-com-
ponent system comprising a hydrophosphoryl and a
carbonyl compounds, and a diaminooligoether, which
provides the target compounds in extremely high
yields. The alternative procedure is a two-stage
process involving the synthesis of the -aminophos-
phine oxide synthon by reaction of a hydrophosphoryl
In the short preliminary report [1] we mentioned
that ion-selective electrodes doped with aza podand
VII can used for determination of cesium and
rubidium ions in the presence of other ions. In the
present work we present the results of a more ex-
tended and thorough investigation of the feasibility
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SYNTHESIS AND IONOPHORIC PROPERTIES OF , -DIPHOSPHORYLATED AZA PODANDS: II. 221
for determination of alkali and alkaline-earth metal
ions of ion-selective electrodes containing aza
podands with tolyl (VII) and octyl (VIII) substituents
on phosphorus. The choice of these two of all our
prepared phosphorylated aza podands (Table 1) was
motivated, first, by the fact that their phosphorus-
containing functional groups are fairly strongly differ
in structure and, consequently, in lipophilicity. Then,
as found by special investigations, these aza podands
exhibit the highest selectivity, among the synthesized
compounds, to heavy alkali and alkaline-earth metal
cations in membrane transport (the results of this
study will be reported elsewhere).
effects the stability of such complexes [4]. In solvents
with a high dielectric permeability, the selectivity of
complex formation with double-charged cations is
higher than with single-charged cations with the same
radius. Therefore, nitroaromatic solvents are usually
used as membrane solvents in ion-selective electrodes
on the basis of neutral carriers sensitive to doble-
charged ions [4].
To study the ionophoric properties of the aza
podands, we made ion-selective electrodes with liquid
membranes. Their construction was analogous to that
described in [14]. The body of the electrode is a poly-
ethylene pipette tip packed with a Teflon powder
impregnated with a liquid membrane. Phosphorylated
2,11-diaza-5,8-dioxadodecanes with tolyl ((VII)) and
octyl (VIII) substituents on phosphorus were used as
active components of the liquid membranes. The
membranes were solutions of the podands in nitro-
benzene or o-nitrophenyl octyl ether containing
equimolar (with respect to carrier) amount of sodium
nitrophenylborate added to suppress the anionic
function of the electrode.
According to published data, the most sensitive to
alkali and alkaline-earth metal cations among neutral
carriers used in ion-selective electrodes are oligoethers
with the low-polarity amido and amino terminal
groups [3, 4], as well as natural antibiotics, such as
nigericin, monensin, and valinomicin [13]. One of the
most important factors controlling the selectivity of
ion-selective electrodes is compliance of the structure
of the carrier to coordination demands of the ion. At
the same time, an important role belongs to correct
selection of the membrane phase, since the electro-
static interaction between the membrane solvent and
the complex of the cation with neutral carrier strongly
Potentiometric measurements with membrane ion-
selective electrodes were carried out in the following
galvanic transfer circuit.
2
Ag AgCl, KCl 1 10 1 10 5 M Membrane 1 10 2 M AgCl Ag.
MCl
MCl
Here M is a metal to be determined. The internal
electrode solution is a standard solution of the cor-
responding salt.
Table 2. Characteristics of ion-selective electrodes with
liquid membranes on the basis of phosphorylated aza
podands VII and VIII
We found that ion-selective electrodes doped with
aza podands VII and VIII give a response on alkali
and alkaline-earth metal ions, and the selectivity of
the electrodes significantly depends on the structure
of the podand. Hence, aza podand VII exhibits the
highest affinity and selectivity to ions of heavy alkali
metals, such as cesium and rubidium.
Cation Detection limit Cmin, M Slope, E/pC(M), mV
Ionophore VII
5
Rb+
Cs+
1.0 10
1.0 10
56.3 1.7
62.7 1.8
5
Ionophore VIII
4
From Table 2 it follows that the electrode contain-
ing this podand is characterized by electrode function
slopes of 56.27 1.65 mV for rubidium cation and
62.7 1.77 for cesium cation. These values are close
to the theoretical slopes found from the Nernst equa-
tion for single-charged cations, which implies rever-
sibility of the processes on the interface. We found
that the described electrode is sensitive to cesium and
Li+
1.0 10
57.9 1.0
44.9 0.3
3
3
4
4
5
5
5
5
Na+
K+
1.0 10
1.0 10
1.0 10
1.0 10
5.0 10
1.0 10
5.0 10
1.0 10
NH+4
Rb+
Mg2+
Ca2+
Sr2+
Ba2+
28.7 1.8
31.1 1.3
29.6 1.5
31.7 1.4
2
rubidium ions in the concentration range 10 10 5 M.
It should be emphasized that a high selectivity of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 2 2005

222
GARIFZYANOV et al.
shows that the aromatic compound exhibits the
E, mV
highest sensitivity to the single-charged rubidium
cation, while its aliphatic analog is the most suitable
for determination of the double-charged barium ion.
However, in both cases podands VII and VIII are
best complementary to larger radius ions, thus pro-
viding one more evidence showing that an ion to be
determined should fit the size of the potenial
pseudocavity.
100
50
0
50
The practical feasibility of ion-selective electrodes
on the basis of phosphorylated aza podands we tested
using the example of electrodes with a podand VII
doped liquid membrane. With this electrode we per-
formed potentiometric titration of rubidium chloride
with sodium tetraphenylborate. The titration curve is
presented in the figure. In the equivalence point we
observe a strong potential jump, which suggest the
applicability of the indicator electrodes for potentio-
metric titration of rubidium salts.
100
0
1
2
3
4
5
6
7
8
V, ml
Potentiometric titration curve of RbCl with the indicator
Hence, we have developed a new type of iono-
phores having the structure of , -aminomethyl-
phosphorylated oligoethers, which can be used as
components of ion-selective electrodes. We have also
established the feasibility of such electrodes for
determination of heavy alkali and alkaline-earth metal
cations in low concentrations in the presence of
sodium, potassium, and ammonium ions.
electrode on the basis of aza podand VII.
the simultaneous determination of potassium and
rubidium ions is attained. The log rubidium/potassium
selectivity coefficient log kpot(Rb+/K+) 1.2, i.e. the
sensitivity to rubidium is more that an order of mag-
nitude higher than to potassium. A still higher selec-
tivity was found for the rubidium/ammonium cation
pair, log kpot(Rb+/NH+4) 1.38. The lowest are the
rubidium/barium (0.72), rubidium/lithium (0.89) and
rubidiun/sodium (0.83) selectivities. Aza podand VII
containing aromatic fragments exhibits the highest
affinity to heavy alkaline and alkaline-earth metal
cations.
EXPERIMENTAL
1
The H and 31P NMR spectra were recorded on a
Varian Unity NMR spectrometer (300 MHz) and on a
custom-made spectrometer with a working frequency
of 8 MHz, external references TMS and 85% phos-
phoric acid. The IR spectra were recorded on a Spe-
cord M-80 spectrometer.
Aliphatic aza podand VIII was found to be the
most selectivite for barium cation. In this case,
log kpot(Ba2+/M) decreases in order K+ (2.24), Na+
(1.82), NH+4 (1.41), Li+ (1.36), Ca2+ (0.75), and Rb+
(0.51). Hence, here, too, complex formation occurs in
preference to the heavy barium ion compared to
ammonium and most alkali metal ions, which allows
barium to be determined in the presence of the latter
ions. Note that the selectivity for the heaviest barium
and rubidium is the lowest. This fact may imply
similarity in the character of complex formation of
these two ions.
The electrode characteristics of ion-selective elec-
trodes were measured after preliminary 24-h exposure
of the membranes to standard solutions of cations to
be determined. The measurements were performed at
constant temperature (20 2 C) under continuous
stirring in a temperature-controlled cell.
Potentiometric measurements with ion-selective
electrodes as indicator electrodes were carried out on
an I-130 pH-meter millivoltmeter. The reference
electrode was an EVL-1M3 silver chloride electrode.
Note that the ion-selective electrode containing
octyl-substituted aza podand VIII is feasible for de-
termination double-charged metal ions (detection limit
The starting dialkylphosphinous acids were ob-
tained according to the procedure in [15] by reactions
of diethyl hydrogen phosphite with the corresponding
5
10 M). The detection limit for light metal ions is
3
4
much lower (10 10 , Table 2).
aryl- or alkylmagnesium halides. Intermediate
-
Comparison of the ionophoric properties of aza
podands with tolyl (VII) and octyl (VIII) substituents
aminophosphine oxide XII was synthesized by means
of the Kabachnik Fields reaction. , -Dibutylamino-
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SYNTHESIS AND IONOPHORIC PROPERTIES OF , -DIPHOSPHORYLATED AZA PODANDS: II. 223
ethers were prepared by alkylation of , -dihaloethers. that, 5.31 g of diamylphosphinous acid in 20 ml of
Reaction progress and product purity were controlled
by TLC on Silufol plates (eluents 1:1 acetonitrile
chloroform and 1:4 acetone chloroform) using re-
ference compounds, developer iodine vapor. For better
visualization the plates were treated with water.
benzene was added, and the reaction mixture was
refluxed with a Dean Stark trap for 6.5 h. Over this
period, 0.7 ml of water (88%) was collected. The
solvent was removed in a vacuum until constant
weight. The residual light yellow oil, 11.6 g, was
purified by column chromatography. Characteristics
of compounds VI XI are listed in Table 1.
Purification of the reaction products was carried
out on a column (70 5 cm) of Silica gel L100/400
(LaChema), eluent 1:9 methanol chloroform. The
sorbent was preliminary exposed to the eluent for
1 day. The samples was diluted with a little chloro-
form before application to the column. The average
time of elution was about 4 h. The solvents were
purified by standard procedures [16].
1,12-Bis[di( p-tolyl)phosphinoyl]-2,11-dibutyl-
2,11-diaza-5,8-dioxadodecane (VII). a. A mixture
of 2.76 g of di(p-tolyl)phosphinous acid, 0.36 g of
Paraform, and 1.56 of compound XII was refluxed in
benzene with a Dean-Stark trap for 40 min. Over this
period, about 95% of water was collected. After that
the mixture was refluxed for an additional 40 min and
then evaporated to constant weight. The residual
viscous liquid was purified by column chromato-
graphy to obtain 3.3 g (74%) of a light yellow viscous
liquid.
1,10-Dibutyl-1,10-diaza-4,7-dioxadecane (IV).
Dibutylamine, 27 g, was heated to boil, and 15 g of
1,8-dibromo-4,7-dioxaoctane was added dropwise.
Addition of each drop was accompanied by heat evo-
lution, and the reaction mixture boiled without heating.
After the addition was complete, the reaction mixture
was refluxed for 5 h, cooled to room temperature, and
washed with a solution of 4.34 g of sodium hydroxide
in 15 ml of water. The product and the aqueous layer
were extracted with ether (3 20 ml), and the com-
bined extracts were dried over sodium sulfate for a
day. The solvent and excess butylamine were removed
in a vacuum. The crude product was distilled in a
vacuum to obtain 6.2 g (32%) of compound IV as a
b. To a solution of 3.05 g of compound V in 20
ml of DMF, 1.32 g of 1,8-dibromo-4,7-dioxaoctane
was added dropwise with stirring at 50 C in the
presence of 0.7 g of potassium carbonate. After the
addition was complete, the reaction mixture was
heated for 5 h at 70 C (bath temperature). After that
it was cooled, washed with water, extracted with
chloroform, and dried oved sodium sulfate. Then
chloroform was removed, and the residue was sub-
jected to a vacuum until constant weight. The crude
20
colorless liquid, bp 122-125 C (38 Pa), nD 1.4513.
Found, %: C 64.52; H 12.43. C14H32N2O2. Calculated, product was purified by column chromatography as
%: C 64.62; H 12.30.
described above to obtain 2.43 g (68%) of product
VII whose Rf and spectral characteristics were similar
to those of the above sample.
(Aminomethyl)butyldi(p-tolyl)phosphine oxide
(V). To solution of 2.92 g of n-butylamine in 20 ml
of benzene, 0.13 g of Paraform was added. The re-
sulting mixture was treated with a solution of 2.3 g of
di(p-tolyl)phosphinous acid in 15 ml of benzene, re-
fluxed with a Dean Stark trap for 4 h, and then let to
stand for 2 h. The residual solvent, butylamine, and
water were removed in a vacuum to give 3.03 g of a
viscous light yellow oil. According to TLC (Silufol,
elution with 4:1 chloroform-acetone), it was an
almost pure compound which can be used in further
syntheses. Crystallization from hexane benzene gave
a pure low-melting crystalline product V, yield after
purification 2.8 g (92%), Rf 0.35 (elution with 4:1
1,12-Bis(dioctylphosphinoyl)-2,11-dibutyl-2,11-
diaza-5,8-dioxadodecane (VIII). A mixture of 6.53 g
of dioctylphosphinous acid, 0.72 g of Paraform, 3.1 g
of compound XII, and 30 ml of benzene was refluxed
for 4 h with the removal of water. After 0.3 ml (75%)
of water evolved, 0.2 g of Paraform was added, and
the resulting mixture was refluxed for 2 h. The solvent
was removed, and the residue was exposed to a
vacuum to constant weight to obtain 9.8 g of a crude
light yellow product which was purified by column
chromatography under the above-described conditions
(eluent 1:1 chloroform acetonitrile) to give 6.5 g
(64%) of a yellow resinous product.
chloroform acetone). 31P NMR spectrum:
42 ppm
P
(benzene). Found, %: C 72.5; H 8.11; P 9.4.
C19H26NOP. Calculated, %: C 72.38; H 8.25; P 9.84.
1,12-Bis(didecylphosphinoyl)-2,11-dibutyl-2,11-
diaza-5,8-dioxadodecane (IX). A mixture of 3.3 g of
didecylphosphinous acid, 0.3 g of Paraform, and 1.3 g
of compound XII was refluxed for 2 h in benzene
with removal of water. After that, the solvent was
removed in a vacuum, the residue was dissolved in
toluene, p-toluenesulfonic acid was added, and the
1,12-Bis(diphenylphosphinoyl)-2,11-dibutyl-
2,11-diaza-5,8-dioxadodecane (VI). To a solution of
5.8 g of 1,10-dibutyl-1,10-diaza-4,7-dioxadecane (XII)
in 30 ml of benzene, 1.34 g of Paraform was added.
Cooling of the reaction mixture was observed. After
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 2 2005

224
GARIFZYANOV et al.
mixture was refluxed for an additional 2 h. A total of
0.2 ml of water (100%) was removed. The mixture
was cooled, washed with aqueous potassium bicar-
bonate and two portions of water, and dried over an-
hydrous magnesium sulfate. The product was purified
by column chromatography to give 3.6 g (76%) of a
resinous product (elution with 1:1 chloroform aceto-
nitrile).
2. Host Guest Complex Chemistry. Macrocycles: Syn-
thesis, Structures, Applications, Vogtle, F. and
Weber, E., Eds., Berlin: Springer, 1985.
3. Kron, T.E. and Tsvetkov, E.N., Usp, Khim., 1990,
vol. 59, no. 3, pp. 483 508.
4. Markovich, I.S. and Dziomko, V.M., Zh. Vses. Khim.
O va, 1985, vol. 30, no. 5, pp. 562 570.
5. Morf, W.E., The Principles of Ion-Selective Elec-
trodes and of Membrane Transport, New York:
Elsevier, 1981.
1,6-Bis(dioctylphosphinoyl)-2,5-dibutyl-2,5-di-
azahexane (X). A mixture of 8.22 g of dioctylphos-
phinous acid, 0.9 g of Paraform, and 2.58 g of N,N -
dibutylethylenediamine was refluxed in toluene with
removal of water for 3 h. Over the reaction period,
0.25 ml of water was collected. The toluene was
removed in a vacuum, and the residue was heated for
6 h at 145 C to obtain 11 g (99%) of a crude product.
Column chromatography gave 8.1 g of a viscous light
yellow liquid.
6. Evreinov, V.I., Baulin, V.E., Vostroknutova, Z.N.,
Bondarenko, N.A., Syundyukova, V.Kh., and Tsvet-
kov, E.N., Izv. Akad. Nauk, Ser. Khim., 1989, no. 9,
pp. 1990 1997.
7. Evreinov, V.I., Baulin, V.E., Vostroknutova, Z.N.,
Safronova, Z.V., Bondarenko, N.A., and Tsvet-
kov, E.N., Zh. Obshch. Khim., 1995, vol. 65, no. 2,
pp. 223 231.
N,N -Bis(didecylphosphinoylmethyl)piperazine
(XI). A mixture of 7.20 g of didecylphosphinous acid,
0.6 g of Paraform, and 0.86 g of piperazine was re-
fluxed in toluene with removal of water. After water
no longer separated, the reaction mixture was refluxed
for an additional 1.5 h, and the toluene was then
removed in a vacuum. The solid residue was twice
crystallized from hexane to give 5.6 g (67%) of a pure
product, white downy crystals.
8. Tsvetkov, E.N., Evreinov, V.I., Baulin, V.E., Ragu-
lin, V.V., Bondarenko, N.A., Vostroknutova, Z.N.,
and Safronova, Z.V., Zh. Obshch. Khim., 1995,
vol. 65, no. 9, pp. 1421 1431.
9. Shvedene, N.V., Berdnikova, L.P., Baulin, V.E., and
Pletnev, I.V., Izv. Akad. Nauk, Ser. Khim., 2000,
no. 10, pp. 1729 1733.
10. Cherkasov, R.A. and Galkin, V.I., Usp. Khim., 1998,
vol. 67, no. 10, pp. 940 968.
11. Garifzyanov, A.R., Mikryukova, E.Yu., and Toropo-
va, V.F., Zh. Obshch. Khim., 1991, vol. 61, p. 1346.
12. Gromov, S.P. and Dmitrieva, S.N., Izv. Ross. Akad.
Nauk, Ser. Khim., 1999, no. 3, pp. 542 545.
13. Ovchinnikov, Yu.A., Ivanov, V.T., and Shkrob, A.M.,
Membrano-aktivnye kompleksony (Membrane-Active
Complex-Forming Agents), Moscow: Nauka, 1974.
14. Garifzyanov, A.R., Khramov, A.N., and Toropo-
va, V.F., Zh. Anal. Khim., 1991, vol. 45, no. 1,
pp. 133 138.
ACKNOWLEDGMENTS
The work was financially supported by the Russian
Foundation for Basic Research (project no. 04-03-
32906), Universities of Russia Basic Research
Program of the Ministry of Education of the Russian
Federation, and the Basic Research and Higher
Education Collaborative Program of CRDF and the
Ministry of Education of the Russian Federation
(project no. REC-007).
15. Kormachev, V.V. and Fedoseev, M.S., Preparativ-
naya khimiya fosfora (Preparative Chemistry of
Phosphorus), Perm: Ural Branch Ross. Akad. Nauk,
1992.
16. Gordon, A.J. and Ford, R.A., The Chemist’s Compa-
nion, New York: Wiley, 1972.
REFERENCES
1. Vasil’ev, R.I., Durmanova, N.V., Garifzyanov, A.R.,
and Cherkasova, R.A., Zh. Obshch. Khim., 2003,
vol. 73, no. 6, p. 1051.
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