Synthesis of novel mono- and bisaminophosphoryl compounds and their membrane transport properties for acidic substrates

Article abstract of DOI:10.1134/S1070363208070062

Some novel aminophosphoryl compounds were synthesized by the Kabachnik-Fields reaction. Their membrane transport properties for mono-and polyfunctional carboxylic acids with different number of functional groups were studied to establish that the transpor

Full text of DOI:10.1134/S1070363208070062

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 7, pp. 1330–1333. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © R.A. Cherkasov, A.S. Talan, A.V. Tarasov, A.P. Garifzyanov, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 7,
pp. 1093–1096.
Synthesis of Novel Mono- and Bisaminophosphoryl Compounds
and Their Membrane Transport Properties for Acidic Substrates
R. A. Cherkasov, A. S. Talan, A. V. Tarasov, and A. P. Garifzyanov
Kazan State University,
ul. Kremlevskaya 18, Kazan, Tatarstan, 420008 Russia
е-mail: rafael.cherkasov@ksu.ru
Received January 29, 2008
Abstract—Some novel aminophosphoryl compounds were synthesized by the Kabachnik–Fields reaction.
Their membrane transport properties for mono- and polyfunctional carboxylic acids with different number of
functional groups were studied to establish that the transport rate of acidic substrates through liquid
impregnated membranes increases in going from mono- to diphosphoryl carriers. Additional hydrophilic
groups in the substrate molecule, too, affect transport efficiency.
DOI: 10.1134/S1070363208070062
Earlier we reported that α- and β-aminated
phosphoryl compounds can be used as selective
extractants for noble metal ions [1, 2] and as
ionophores in ion-selective electrodes [3]. They are
also of undoubtful interest as carriers in membrane
extraction of organic and inorganic substrates [4, 5].
Research on the influence of the structure of
functionalized phosphoryl carriers on the efficiency of
membrane transport of proton–donor substrates [4] and
phase transfer of metal ions [2, 6] established that the
complexing ability of phosphoryl extractants is af-
fected by “additional” donor functional groups. Mono-
and diphosphorylated phosphine oxides have never
been compared as membrane carriers for proton-donor
substrates. Phosphine oxide carriers are obviously
advantageous over their phosphonate analogs in being
hydrolytically more stable in acidic and alkaline media.
organic acids are given in the table. The one-pot
syntheses of compounds I–-V were carried out in the
three-component system formaldehyde–-octylamine–-
dihexyl phosphinite (for I) or dioctyl phosphinite (for
II). Phosphonate III was synthesized from bis(2-
ethylhexyl)amine and dicyclohexyl hydrogen phos-
phite. Phosphorylated amine II was, in its turn, used as
the amine component in the three-component
Kabachnik–Fields system, along with formaldehyde
and dihexylphosphinous acid to synthesize diphos-
phorylated amine IV. The synthesis of γ-aminophos-
phonate V was carried out in three stages. In the first
stage we obtained diisopropyl (3-chloropropyl)phos-
phonate by selective substitution of bromine in 1-
chloro-3-bromopropane with sodium diisopropyl
phosphite by the Michaelis–Becker reaction [8]. The
product was refluxed in excess butylamine to obtain
the corresponding γ-(N-butylamino)phosphonate whose
Kabachnik–Fields reaction with formaldehyde and
dioctyl phosphinite gave diphosphorylated amine V
with high yield. We developed a procedure for puri-
fication of aminophosphine oxides, according to which
the latter are converted into crystalline oxalic acid salts
in diethyl ether, and the oxalates are recrystallized and
treated with aqueous alkali to recover the neutral form.
In the present work we synthesized novel α-
aminophosphine oxides of various nature and studied
their membrane transport properties for proton-donor
substrates. Using the Kabachnik–Fields reaction we
obtained a number of amines of the phosphonate and
phosphine oxide structures with various mutual
arrangements of the nitrogen and phosphorus atoms,
one or two phosphorus-containing groups, and, for a
required hydrophilic–lypophilic balance, fairly long-
chain substituents at the potential coordination centers
[7]. Their formulas and the transport flows rates of
Our obtained aminophosphoryl carriers were
investigated as carriers for membrane extraction of
medium-strength organic acids with different numbers
1330

SYNTHESIS OF NOVEL MONO- AND BISAMINOPHOSPHORYL COMPOUNDS
1331
Membrane transport flow rates of organic acids with aminophosphoryl compounds R2P(O)CH2NR1R2
Carrier
Flow rate×106 mol min–1m2
Comp. no.
R
R1
Oct
R2
Acetic acid
Glutaric acid
Tartaric acid
Citric acid
Hex
Oct
H
170
190
200
460
420
79
260
0.294
240
330
0.026
2.3
19
95
13
30
23
I
Oct
H
II
III
IV
V
cyclo-HexO
Hex
2-EtHex
Oct
2-EtHex
0.066
18
CH2P(O)Hex2
Oct
Bu
(CH2)3P(O)(ОPr-i)2
11
of functional groups: acetic, glutaric, tartaric, and
citric. We considered it important and interesting to
choose specifically this series of acids, since the
consecutive increase in the number of the hydrophilic
carboxy and hydroxy groups was expected to affect
strongly the ability of the acids “to employ” certain
basic centers of carriers and also to form complexes
with hydrogen bonds of various strength with was
molecules in the feed phase.
donor and the corresponding basic center of the partner
[4]. In this case, the extraction efficiency will be
defined by the hydration energy of the acid molecule
and the energy of the forming hydrogen bond, i.e. by
the strength of the arising carrier–acid associate and its
hydrophilicity. It is quite probable that our studied
carriers and acids, too, form such associates.
Interrelationships between the structure and
transport properties of carriers are commonly not
sufficiently simple, since the transport efficiency is
dependent both the rate of carrier-substrate bonding
and on the facility of re-extraction in the receiving
phase. Moreover, polyfunctional complex-forming
agents, like our studied aminophosphoryl compounds,
not always employ simultaneously all their coordina-
tion centers in bonding with the transported substrate,
say, by steric reasons.
We carried out the purposeful selection of the
structure of aminophosphoryl carriers in view of the
fact that, as we earlier established [4], the most
effective membrane transport of acids with function-
alized phosphoryl compounds containing hydroxy,
alkoxy, and amino groups in various positions to the
phosphorus atom is observed with the latter deriv-
atives: Aminophosphonates provide much higher
transport flow rates compared to oxygen analogs.
Hydrogen bonding of transported acidic substrates is
obviously much stronger with nitrogen centers than
with oxygens. The second phosphoryl group in the
carrier molecule, α (IV) or γ (V) to nitrogen, not only
affects (decreases) the electron density on the latter
[9], but also creates obvious steric hindrances to
complex formation, especially with large molecules of
polyfunctional acids. Thus we had a good chance to
assess the efficiency and selectivity of membrane
extraction and concentration of acidic substrates by
selecting complementary substrate–-aminophosphoryl
carrier pairs.
Nevertheless, the results presented in the table
reveal fair correlations between the structure of the
complex-forming partners and the transport flow rates.
This correlation is especially clear in the case of the
monobasic acetic acid. Comparison of the flow rates of
amines I–V provides unequivocal evidence showing
that the nitrogen atom is the protonation center of the
carrier, and the phosphoryl oxygen is not involved in
bonding with the substrate. As we showed earlier [4],
the efficiency of nitrogen-free phosphoryl carriers for
monobasic acids is much enhanced when the electron-
acceptor alkoxy substituents on phosphorus are
replaced by the donor alkyl groups. In this case, the
transport flow rate over the series phosphine oxide I,
II, phosphonate III remains almost unchanged.
The low-polarity phenylcyclohexane was chosen as
a membrane solvent to exclude the possibility of
specific solvation of both carriers and complexes
formed in the membrane phase.
At the same time, with diphosphorylated amines,
the transport flow rate of acetic acid increases sharply,
implying that it is the phosphoryl group that is
involved in H-complex formation with the substrate.
It is known that weak organic and inorganic acids
are extracted by the solvate mechanism, which
assumes formation of H-complexes between the proton
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1332
CHERKASOV et al.
There are two possible reasons for the “inclusion” in
bonding of an additional basic center, the oxygen
atom. On the one hand, tertiary amines, such as
carriers IV and V, are incapable of forming intra-
molecular hydrogen bonds, which, as we showed
earlier [10], can seriously affect the acid–base
properties of aminophosphoryl compounds. This
makes additional coordination centers available for
protonation, even though the structure of the resulting
complexes (simultaneous H-bonding with two or three
centers and complex formation with two or three acid
molecules at once) is difficult to establish from the
available data.
obviously connected just with a high hydrophilicity of
the H-complexes of phosphorylated amines with these
substrates, since the carriers have not enough basic
centers for bonding with all their proton-donor
functional froups. The excess nonbound hydroxy and
carboxy groups form hydrogen bonds with water
molecules and thus keep the substrates in the feed
phase.
Thus, the present results provide evidence for our
earlier conclusion that efficient membrane transport of
substrates of various nature is provided exclusively by
complementary carrier-substrate interactions. Thus, in
the transport of metal ions with phosphorylated aza
podands [6] or in the use of aminophosphoryl
compounds in ion-selective electrodes [3], of im-
portance is for the ion size to be compatible with the
size of the potential pseudo-cavity formed by the
podand. Acid–base interactions of a proton donor with
potential electron-donor centers of the complex-
forming agent and presence or absence of “additional”
hydrophilic groups in the substrate should also be
taken into account in considering membrane transport
of acidic substrates. Evidently, features of the
hydrophylic–lipophilic balance both in the carrier and
in its formed complex, too, should be taken into
consideration, even though this factor is fairly difficult
to evaluate explicitly. This relates to full measure to
steric factors essential on the formation of complexes
transferred into the membrane phase. Nevertheless, the
revealed trends in variation of the transport properties
of carriers as a function of their and transported
substrate structure allow optimization of membrane
transport processes by selection of complementary
substrate–carrier pairs.
The “structure–transport efficiency” interrelation-
ship for the dibasic glutaric acid is less unequivocal. In
this case, diphosphoryl carriers, too, tend to provide a
more efficient transport, but this tendency is not as
well-defined as with the monobasic acid substrate. The
high flow rate with phosphine oxide II is attributable
to the involvement of both the carboxylic groups in
protonation of the two basic centers of the phos-
phorylated amine, as may also be the case with
diphosphorylated amines IV and V. In this respect
quite illustrative is an almost 1.5-fold difference in the
efficiency of the latter two amines: α,α-Diphos-
phylamine IV is highly sterically congested, and,
therefore, the nitrogen center in it is shielded and less
accessible than in its α,γ-analog V. The reason for the
low efficiency of transport of glutaric acid with
phosphine oxide I and, especially, phosphonate II can
consist in an unfavorable hydrophylic-lipophilic
balance of the carriers (we earlier observed such
distinction when varied the length of the hydrocarbon
groups on phosphorus in a membrane transport study
on phosphorylated aza podands [6]). Another possible
explanation of the observed phenomenon is the
presence of the second hydrophilic carboxy group
which is not bonded with the carrier but has a strong
hydrogen bond with the medium and thus keeps the
substrate in the feed phase. However, the lack of
transfer with complex formation in the case of
phosphonate II can be connected with its specific
properties, for example, poor solubility in the organic
membrane phase.
EXPERIMENTAL
Equipment and technique of the membrane
transport study are described in [5]. Vladipor МFFK-4
filters, pore size 0.1 μm, impregnated with 0.1 M
solutions of carriers in phenylcyclohexane were used
as impregnated membranes. The initial concentration
of carboxylic acids in the feed solution was 0.1 M.
Synthesis of aminophosphoryl compounds by the
Kabachnik–Fields reaction (general procedure). A
solution of 0.3 mol of dialkyl phosphinite or phos-
phite, 0.3 mol of Paraform, 0.3 mol of amine, and a
small amount of p-toluenesulfonic acid in 30 ml of
solvent (benzene, toluene, or o-xylene) was refluxed
with a Dean–Stark trap until water no longer released.
The effect of an “additional” hydrophilic group,
which we observed earlier on transport of dicarboxylic
and hydroxy acids with functionalized phosphoryl
carriers [4], revealed itself to full measure in the
present reaserch, too. The low transport flow rates for
di- and trihydroxy acids, such as tartaric and citric, are
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 7 2008

SYNTHESIS OF NOVEL MONO- AND BISAMINOPHOSPHORYL COMPOUNDS
1333
A calculated quantity of Na2CO3 was added to remove
ACKNOWLEDGEMENTS
the catalyst. The reaction mixture was washed with
water, and the aqueous layer was extracted with
benzene. The organic fractions were combined and
dried over anhydrous magnesium sulfate. The solvent
was removed in a rotary evaporator. The crystalline or
oily residue was treated with a calculated quantity of
oxalic acid in diethyl ether. White crystals precipitated
and were recrystallized from acetone and then treated
with aqueous alkali until neutral reaction. The target
aminophosphoryl compound was extracted with
toluene, dried over anhydrous magnesium sulfate, and
the solvent was removed under a vacuum.
The work was financially supported by the Russian
Foundation for Basic Research (project no. 07-03-
00306).
REFERENCES
1. Cherkasov, R.A., Garifzyanov, A.R., Zakharov, S.V.,
Vinokurov, A.I., and Galkin, V.I., Zh. Obshch. Khim.,
2006, vol. 76, no. 3, p. 438.
2. Garifzyanov, A.R., Zakharov, S.V., Кryukov, S.V.,
Galkin, V.I,. and Cherkasov, R.A.., Zh. Obshch. Khim.,
2005, vol. 75, no. 8, p. 1273.
Dihexyl(N-octylaminomethyl)phosphine oxide (I).
Yield 70%, mp 35°C. 31P NMR spectrum (toluene): δP
48 ppm. IR spectrum, ν, cm–1: 1159 (P=O). Calcul-
ated, %: P 8.61; N 3.90. C21H46NOP. Found, %: P
8.60; N 3.89.
3. Cherkasov, R.A., Nuriazdanova, G.Kh., and Garifzya-
nov, A.R., Zh. Obshch. Khim., 2006, vol. 76, no. 2, p. 215.
4. Cherkasov, R.A, Garifzyanov, A.R., Krasnova, N.S.,
Cherkasov, A.R., and Talan, A.S., Zh. Obshch. Khim.,
2006, vol. 76, no. 10, p. 1603.
Dioctyl(N-octylaminomethyl)phosphine oxide (II).
31
Yield 80% mp 48°C. P NMR spectrum (toluene): δP
5. Garifzyanov, A.R., Shyrshova, N.V., and Cherkasov, R.A.,
Zh. Obshch. Khim., 2005, vol. 75, no. 4, p. 575.
48 ppm. IR spectrum, ν, cm–1: 1161 (P=O). Calculated,
%: P 7.45; N 3.37. C25H54NOP. Found, %: P 7.41; N
3.32.
6. Cherkasov, R.A., Garifzyanov, A.R., Vasilyev, R.I., and
Talan A.S., Zh. Obshch. Khim., 2008, vol. 78 no. 6, p. 940.
Dicyclohexyl [N,N-bis(2-ethylhexyl)aminomethyl]-
7. Garifzyanov, A.R., Nuriazdanova, G.Kh., Zakharov, S.V.,
and Cherkasov R.A., Zh. Obshch. Khim., 2004, vol. 74,
no. 12, p. 1998.
31
phosphonate (III). Yield 70%, nD20 1.4729. P NMR
spectrum (toluene): δP 25 ppm. IR spectrum, ν, cm–1:
1246 (P=O). Found, %: P 5.54; N 2.76. C29H58NO3P
Calculated, %: P: 6.20; N: 2.80.
8. Каbachnik, М.I., Godovikov, N.N., and Godina, E.I.,
Zh. Obshch. Khim., 1963, vol. 33, no. 7, p. 1355.
Dihexyl[[N-octyl-N-(dihexylphosphinoylmethyl)
amino]methyl]phosphine oxide (IV). Yield 50%, nD20
1.4729. 31P NMR spectrum (toluene): δP 44 ppm. IR
spectrum, ν, cm–1: 1165 (P=O).
9. Cherkasov, R.A., Galkin, V.I., Khusainova, N.G., Mos-
tovaya, O.A., Garifzyanov, A.R., Nuriazdanova, G.Kh.,
Krasnova, N.S., and Berdnikov E.A., Zh. Org. Khim.,
2005, vol. 41, no. 10, p. 1511.
{[N-Butyl-N-[3-(diisopropoxyphosphinoyl)propyl]-
amino]methyl}dioctylphosphine oxide (V). Yield 40%,
nD20 1.4651. 31P NMR spectrum (toluene), δP, ppm: 45, 31.
10. Zakharov, S.V., Nuriazdanova, G.Kh., Garifzyanov, A.R.,
Galkin, V.I., and Cherkasov, R.A., Zh. Obshch. Khim.,
2004, vol. 74, no. 6, p. 946.
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