N-diphenylphosphorylureas on the basis of natural α-amino acid esters: One-pot synthesis and extraction properties

Full text of DOI:10.1134/S0012500811060012

ISSN 0012ꢀ5008, Doklady Chemistry, 2011, Vol. 438, Part 2, pp. 151–154. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © E.I. Goryunov, A.E. Shipov, I.B. Goryunova, G.K. Genkina, P.V. Petrovskii, A.O. Borisova, A.M. Safiulina, I.G. Tananaev, E.E. Nifant’ev, B.F. Myasoedov,
2011, published in Doklady Akademii Nauk, 2011, Vol. 438, No. 4, pp. 480–484.
CHEMISTRY
NꢀDiphenylphosphorylureas
on the Basis of Natural ꢀAmino Acid Esters:
α
OneꢀPot Synthesis and Extraction Properties
E. I. Goryunova, A. E. Shipova, I. B. Goryunovaa, G. K. Genkinaa, P. V. Petrovskiia,
A. O. Borisovaa, A. M. Safiulinab, Corresponding Member of the RAS I. G. Tananaevb,
Corresponding Member of the RAS E. E. Nifant’eva, and Academician B. F. Myasoedovb
Received December 28, 2010
DOI: 10.1134/S0012500811060012
We have shown recently that
phoryl)ureas R2P(O)NHC(O)NHR' (
ꢀdiphenylphosphorylated derivatives (Ia, R = Ph),
are highꢀperformance extractants for the recovery of
actinides and lanthanides from nitric acid solutions
[1]. To date, extraction properties were studied for
ureas Ia containing alkyl, aralkyl, and cycloalkyl
groups as substituent R' at the terminal nitrogen;
Nꢀ(diorganylphosꢀ tant that the use of these esters opens a unique opporꢀ
tunity to design both optically inactive (for example,
starting from glycine esters) and chiral phosphorusꢀ
and nitrogenꢀcontaining ligands (when the esters of
I), especially
N
Lꢀαꢀamino acids are employed) on the basis of a uniꢀ
form approach. It should be also noted that ꢀdipheꢀ
N
nylphosphorylated ureas based on the esters of natural
amino acids may be of real interest as biologically
active compounds [6].
N
ꢀdiphenylphosphorylꢀ
Ph2P(O)NHC(O)NНAlk prepared from commerꢀ
cially available and cheap ꢀalkylamines was found to
N'ꢀnꢀalkylureas (DPPAUs)
At present, only few compounds of this family of
ꢀphosphorylureas are described in the literature, all
N
n
the compounds being prepared from neat dipheꢀ
nylphosphoryl isocyanate Ph2P(O)NCO (II) as the iniꢀ
tial organophosphorus reagent [6, 7]. Although this
compound became available when we developed a
simple and efficient catalytic method for the synthesis
of phosphoryl isocyanates [8], the necessity to isolate
isocyanate II in pure state inevitably leads to a subꢀ
stantial deterioration of the environmental and ecoꢀ
nomic characteristics of any synthetic processes on its
basis.
be the most efficient extractants [1–3], which conꢀ
siderably exceed in efficiency and selectivity strucꢀ
turally related diphenyl(carbamoylmethyl)phosꢀ
phine oxides [1].
Therefore, in the context of a search for new
extractants of practical interest among
lated ureas , it is promising to modify DPPAUs by
introduction of different functional groups, especially
those capable of complexing with ꢀelements, into the
Nꢀphosphoryꢀ
I
f
alkyl fragment of these molecules. Taking into account
that the most rational approach to the synthesis of
phosphorylureas I consists in the reaction of phosphoꢀ
ryl isocyanates with amines [4, 5], the initial functionꢀ
alized amines should be sufficiently available and
inexpensive to make modified DPPAUs commercially
appealing, which is a necessary condition for their furꢀ
ther utilization as extractants. Alkyl esters of natural
amino acids best meet these requirements. It is imporꢀ
Recently, we have developed and patented a simꢀ
ple, efficient, and industrially applicable oneꢀpot
method for the synthesis of DPPAUs using cheap
technicalꢀgrade chlorodiphenylphosphine Ph2PCl
(III) as the initial organophosphorus compound,
while intermediate isocyanate II reacted in situ [9].
Later, this method was extended to the preparation of
a great variety of
Nꢀdiphenylphosphorylated ureas
[10], however, it was not applied to the synthesis of
such ureas based esters of amino acids, including natꢀ
ural amino acids.
a Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences, ul. Vavilova 28, Moscow,
119991 Russia
b Frumkin Institute of Physical Chemistry and
Electrochemistry, Russian Academy of Sciences,
Leninskii pr. 31, Moscow, 119991 Russia
In this work, we obtained for the first time a series
Nꢀdiphenylphosphorylureas containing fragments
of
of natural amino acids starting from chlorophosphine
III and esters of these acids with the use of a threeꢀ
stage oneꢀpot process (Scheme 1).
151

152
GORYUNOV et al.
SO Cl
NaOCN, [MgCl ]
2
MeCN
2
CCl
2
Ph2PCl
[Ph2P(O)Cl]
[Ph2P(O)NCO]
4
III
IV
II
H NCHRCOOMe
2
Va–Vc
Ph2P(O)NHC(O)NHCHRCOOMe
VIa–VIc
[V, VI: a) R = H, b) R = CH COOMe, c) R = CH CH COOMe].
2 2 2
Scheme 1.
tal analysis and 1H, 1H{31P}, and 31Р{1H} NMR specꢀ
At the first stage of the process, the initial chloroꢀ
1
phosphine is oxidized to form diphenylchlorophosphꢀ
inate (IV), which reacts with sodium cyanate in the
presence of anhydrous magnesium chloride as a cataꢀ
lyst (2.5 mol %) at the second stage to give isocyanate
II. At the final stage, the isocyanate as a solution in
tra. The H NMR spectra of compounds VIb
,
VIc
show the complicated character of CH2 proton signals.
This effect is undoubtedly results from the presence of
an asymmetric carbon atom in the molecules of these
ureas that causes the geminal protons of the methylene
groups to become diastereotopic and hence magnetiꢀ
cally nonequivalent.
acetonitrile reacts with amino acid esters (Va
produce corresponding ureas (VIa VIc). The initial
amino acid esters used were methyl ester of glycine
Va ), the simplest natural amino acid, and dimethyl
esters of dibasic ꢀamino acids: ꢀaspartic (Vb) and
ꢀglutamic (Vc). All three stages of the oneꢀpot proꢀ
–Vc) to
–
Ureas VIa–VIc are colorless crystalline solids staꢀ
(
ble in air and melting without decomposition. They
are readily soluble in dimethyl sulfoxide, poorly soluꢀ
ble in acetonitrile, and practically insoluble in ether,
hexane, and heptane. All the three ureas are satisfacꢀ
torily soluble in chloroform and deuteriochloroform,
α
L
L
cess occur at a rather high rate even at ambient temꢀ
perature and produce no marked amounts of byprodꢀ
ucts according to 31Р{1H} NMR data, this fact makes
the obtained solutions of compounds VIb
, VIc being
it possible to prepare ureas VIa–VIc that require no
completely stable in time, while a solution of urea VIa
in CDCl3 after several hours produces a crystalline
product; according to Xꢀray diffraction analysis, the
product is a solvate of compound VIa with one CDCl3
molecule (Fig. 1).
additional purification in a yield of 90–91%. It should
be noted, however, that such high yields of the target
compounds were achieved only after the development
of ingenious procedures for the treatment of reaction
mixtures, which substantially differ from the proceꢀ
dures of DPPAUs isolation disclosed in the patent [9].
We have studied the extraction of U(VI) and
The structure of ureas VIa
–VIc obtained by the Nd(III) with 0.05 M solutions of ureas VIb and VIc in
oneꢀpot method was confirmed by the data of elemenꢀ chloroform in a wide range of nitric acid concentraꢀ
O(1)
O(2)
C(10)
C(9)
N(1)
N(2)
P(1)
C(3)
C(5)
C(1)
C(2)
O(3)
O(4)
H(2N)
H(1N)
C(4)
C(11)
C(12)
C(8)
C(16)
C(6)
C(13)
C(14)
C(7)
C(15)
Fig. 1. Structure of compound VIa with the atoms shown by 50% probability thermal ellipsoids.
DOKLADY CHEMISTRY Vol. 438
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N
ꢀDIPHENYLPHOSPHORYLUREAS
153
tions (0.06–5.15 M). In the case of uranium, the disꢀ
tribution ratios were found to increase with HNO3
concentrations for both phosphorus–nitrogen ligands
(Fig. 2). Urea VIc proved to be a more efficient extracꢀ
tant within the entire range of acid concentrations, the
maximum difference in efficiency was observed at
DU(VI)
40
2
1
30
20
10
= 0.06 M (DU(VI) = 1.5 for VIb and 25 for VIc).
c
HNO3
Moreover, in contrast to the all types of
Nꢀdipheꢀ
nylphosphorylated ureas, including DPPAUs previꢀ
ously studied by us, these ligands show a unique capaꢀ
bility to extract uranyl nitrate even from neutral aqueꢀ
ous solutions, which significantly extends the area of
their possible practical application. Compound VIc is
the most efficient in this context (DU(VI) = 7.22). Phosꢀ
phorylureas VIb, VIc extract Nd(III) from nitric acid
solutions with much lower distribution ratios than
those for U(VI).
2
4
6
0
cHNO , M
3
Fig. 2. Extraction of U(VI) with 0.05 M solutions of ureas
VIb and VIc in chloroform depending on the HNO conꢀ
centration (phase ratio is 1 : 1). Compounds: (
3
1) VIb and
(
2
)
VIc
.
chromator,
ω scanning), and 5340 independent reflecꢀ
Thus, we have found a new type of phosphorusꢀ
and nitrogenꢀcontaining ligands showing unusual
extraction properties and developed a simple and
industrially applicable method for their synthesis.
tions (Rint = 0.0395) were used in further refining. The
structure was solved by direct methods and refined by
least squares in the fullꢀmatrix anisotropic–isotropic
2
approximation on
. Hydrogen atoms were located
Fhkl
from difference Fourier syntheses of electron density
and refined in the isotropic approximation. For comꢀ
pound VIa, the refinements converged to R1 = 0.0550
EXPERIMENTAL
1H, 1H{31P}, and 31Р{1H} NMR spectra of the
obtained compounds were recorded on a Bruker
AVꢀ400 spectrometer (operating at 400.13 MHz for
1H and 1H{31P} and at 161.98 MHz for 31P{1H}). Solꢀ
vents used were CDCl3 and (CD3)2SO, concentration
was 0.05 M, residual proton signals of the deuterated
(calculated on Fhkl for 4147 reflections with I > 2σ(I)],
2
wR2 = 0.1182 (calculated on
for all 5340 reflecꢀ
Fhkl
tions), the number of refinement parameters was 252,
GOF = 1.001. The calculations were performed with
the SHELXTL 5.10 program suit [12].
1
solvent were used as an internal reference for H and
1H{31P} NMR, and 85% H3PO4 was used as an exterꢀ
nal reference for 31Р{1H} NMR spectra.
Oneꢀpot synthesis of methyl ester of Nꢀ[Nꢀ(dipheꢀ
nylphosphoryl)carbamoyl]glycine (VIa). A solution of
0.9 g (6.7 mmol) of freshly distilled SO2Cl2 in 2 mL of
anhydrous CCl4 was added dropwise to a magnetically
stirred solution of 1.19 g (5.4 mmol) of chlorophosꢀ
phine III in 5 mL of anhydrous CCl4 under an argon
atmosphere at ambient temperature for 40 min, stirred
for additional 20 min at the same temperature, the solꢀ
vent and other volatile components of the reaction
mixture were removed in a vacuum. The residue was
dissolved in 10 mL of anhydrous MeCN, 13 mg
(0.136 mmol) of finely divided anhydrous MgCl2 was
added, the mixture was stirred until complete dissoluꢀ
tion of the catalyst, 0.7 g (10.8 mmol) of NaOCN was
added, and the mixture was stirred for 1 h at ambient
temperature. Methyl ester Va (0.48 g, 5.39 mmol) was
added dropwise to the obtained suspension, the mixꢀ
ture was stirred for 1 h at ambient temperature, and the
solvent was removed in a vacuum. A 17% aqueous
NaCl solution (15 mL) was added to the residue, and
the mixture was stirred for 1 h at ambient temperature.
The precipitate was separated, washed with ice water
Chlorodiphenylphosphine (Acros, technical
grade) was distilled in a vacuum, NaOCN (Aldrich,
96%) was dried for 4 h at 120
Р2О5, and carbon tetrachloride and acetonitrile were
distilled over Р2О5 prior to use. Methyl esters of
amino acids Va Vc were isolated from corresponding
°C in a vacuum over
α
ꢀ
–
hydrochlorides (Acros and Aldrich, 98–99%) immeꢀ
diately before the reaction by the known procedure
[11].
Elemental analyses were carried out in the Laboraꢀ
tory of Microanalysis (Nesmeyanov Institute of Orgaꢀ
noelement Compounds, Russian Academy of Sciꢀ
ences).
At 120 K, the crystals of VIa
hombic, space group Pbca = 17.677(3) Å,
10.248(2) Å, = 22.194(5) Å,
= 4021(1) Å3,
= 1), dcalc = 1.492 g cm–3 = 5.61 cm–1
(000) =
⋅ СDCl3 are orthorꢀ
,
a
b =
c
V
Z = 8
(Z
'
,
μ
,
F
1856. The intensities of 41 756 reflections were meaꢀ
sured at 100 K with a Bruker AXS SMART 1000 difꢀ
fractometer (λ(MoKα) = 0.71073 Å, graphite monoꢀ
(2 × 5 mL), dried in air, extracted with boiling chloroꢀ
DOKLADY CHEMISTRY Vol. 438
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2011

154
GORYUNOV et al.
form (
4
×
20 mL), and the solvent was removed from (diphenylphosphoryl)carbamoyl]ꢀ
Lꢀglutamic
acid
the extract. The residue was dried in vacuum
~1 mmHg, 90 С, 15 h) to give 1.63 g of methyl ester
of ꢀ[ ꢀ(diphenylphosphoryl)carbamoyl]glycine
VIa). Yield 91%, mp 170–172
For C16H17N2O4P anal. calcd. (%): C, 57.83; H,
(
VIc). Yield 90%, mp 176.5–178.5°C.
(
°
For C20H23N2O6P anal. calcd. (%): C, 57.42;
N
N
H, 5.54; N, 6.70; P, 7.40.
(
°С.
Found (%): C, 57.34; H, 5.50; N, 6.54; P, 7.38.
1H NMR (CDCl3,
1H, СНСНАНВ), 2.04–2.16 (m, 1H, СНС
.16–2.29 (m, 2H, 2СООСН3), 3.59 (s, 3H,
СН2СООСН3), 3.61 (s, 3H, СНСООСН3), 4.30–
4.39 (m, 1H, CH), 7.27 (d, 1H, СНN
3JHH = 7.9),
7.36–7.48 (m, 4H, С6Н5), 7.49–7.58 (m, 2H,
δ, ppm,
J, Hz): 1.81–1.97 (m,
5.16; N, 8.43; P, 9.32.
Н
АНВ),
Found (%): C, 57.74; H, 5.05; N, 8.31; P, 9.28.
2
СН
1Н [(CD3)2SO,
δ, ppm, J, Hz): 3.63 (s, 3H,
CH3O), 3.83 (d, 2H, СН2N, 3JHH = 5.5), 6.88 (t, 1H,
H,
3
NH, JHH = 5.5), 7.46–7.55 (m, 4H,
mꢀC6H5), 7.58
mꢀ
pꢀ
3
(t, 2H,
p
ꢀC6H5, JHH = 6.6), 7.75 (dd, 4H, ꢀC6H5,
o
C6H5), 7.71–7.85 (m, 4H,
NHP(O), 2JHР = 9.6).
oꢀC6H5), 7.96 (d, 1H,
1
3
3JHH = 7.3, JHР = 12.3), 8.72 (d, 1H, NHP(O),
2JHР = 10.6).
31Р{1H} NMR (CDCl3,
δ, ppm): 24.89 s.
31P{1H} NMR ((CD3)2SO,
Oneꢀpot synthesis of dimethyl ester of
(diphenylphosphoryl)carbamoyl]ꢀ ꢀaspartic acid (VIb).
δ, ppm): 15.59 s.
Extraction properties of ureas VIb and VIc were
studied as described in [3].
Nꢀ[Nꢀ
L
Dimethyl ester Vb (0.81 g, 5.03 mmol) was added
dropwise to the acetonitrile solution of isocyanate II
obtained by the above procedure from 1.11 g
(5.03 mmol) of chlorophosphine III, the mixture was
stirred for 1 h at ambient temperature, the solvent was
removed in a vacuum, 15 mL of a 17% aqueous NaCl
solution was added to the residue, and the mixture was
stirred for 1 h at ambient temperature. The precipitate
ACKNOWLEDGMENTS
This work was supported by the Russian Acadꢀ
emy of Sciences (the Program of the Presidium of
the RAS no. Pꢀ7 “Development of Methods for
Preparing Chemical Compounds and Designing
New Materials”).
was separated, washed with ice water (2
dried in air to give 1.82 g of dimethyl ester of
(diphenylphosphoryl)carbamoyl]ꢀ ꢀaspartic
VIb). Yield 90%, mp 180–182
For C19H21N2O6P anal. calcd. (%): C, 56.44; H,
×
5 mL),
ꢀ[
acid
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N
N
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δ
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DOKLADY CHEMISTRY Vol. 438
Part 2
2011