Carbamoylmethylphosphinoxide derivatives based on the triphenylmethane skeleton. Synthesis and extraction properties

Article abstract of DOI:10.1021/jo050717a

Two different strategies were used to synthesize tri(2-alkoxy-5- nitrophenyl)methanes 6a,b. The X-ray structures of 6a and its precursor 5 show the molecules in a conformation with a syn-orientation of the nitro and alkoxy groups. Hydrogenation and acylat

Full text of DOI:10.1021/jo050717a

Carbamoylmethylphosphinoxide Derivatives Based on the
Triphenylmethane Skeleton. Synthesis and Extraction Properties
Valentyn Rudzevich,†,‡ Dieter Schollmeyer,§ Damien Braekers,| Jean F. Desreux,*,|
Romain Diss, Georges Wipff,*, and Volker Bo¨hmer*,†
Abteilung Lehramt Chemie, Fachbereich Chemie und Pharmazie and Institut fu¨r Organische Chemie,
Johannes Gutenberg-Universita¨t Mainz, Duesbergweg 10-14, D-55099 Mainz, Germany,
Coordination and Radiochemistry, University of Lie`ge, Sart Tilman B16/B6, B-4000 Lie`ge, Belgium, and
Laboratoire MSM, Institut de Chimie, UMR CNRS 7551, Universite´ Louis Pasteur, 4, rue B. Pascal,
67 000 Strasbourg, France
jf.desreux@ulg.ac.be; wipff@chimie.u-strasbg.fr; vboehmer@mail.uni-mainz.de
Received April 11, 2005
Two different strategies were used to synthesize tri(2-alkoxy-5-nitrophenyl)methanes 6a,b. The
X-ray structures of 6a and its precursor 5 show the molecules in a conformation with a
syn-orientation of the nitro and alkoxy groups. Hydrogenation and acylation by the appropriate
active ester gave the corresponding tri-CMPO derivatives 4a,b. Their ability to complex lanthanide
ions was studied by NMR spectroscopy and by nuclear magnetic relaxation dispersion and further
characterized by quantum mechanical calculations. Extraction experiments from acidic solution to
dichloromethane reveal a reasonable selectivity of Am(III) over Eu(III), but in contrast to similar
tetra-CMPOs derivatives of calix[4]arenes the distribution coefficients strongly decrease with
increasing concentration of HNO3.
Introduction
elements provided an efficient separation from the lan-
thanides can be achieved.
The appropriate treatment and storage of nuclear
wastes from technical, military, or medical (or other)
sources is one of the permanent and urgent problems of
modern/industrial/civilized societies. Consequently, what-
ever the envisaged strategies are, there is a continuous
search for improved ligands/extractants which are able
to remove the most harmful elements from the total
waste, usually those elements/isotopes with long half-
lifes. In the case of actinides this would not only lead to
a reduction of the total waste volume to be stored but
would also allow for a transmutation into less dangerous
Carbamoylmethylphosphine oxides (CMPOs) represent
such a general class of compounds,1 able to extract
actinides from highly acidic solutions, and N,N-diisobu-
tylcarbamoylmethyloctylphenylphosphine oxide is used
industrially in the TRUEX process.2 In a series of studies,
we could show that the attachment of four CMPO
functions at the wide rim (1)3 or at the narrow rim (2)4
of calix[4]arenes leads to a drastic increase of the
extraction efficiency, suggesting a cooperative action of
(1) (a) Martin, K. A.; Horwitz, E. P.; Ferraro, J. R. Solvent Extr. Ion
Exch. 1986, 4, 1149-1169. (b) Baker, J. D.; Mincher, B. J.; Meikrantz,
D. H.; Berreth, J. R. Solvent Extr. Ion Exch. 1988, 6, 1049-1065.
(2) (a) Horwitz, E. P.; Kalina, D. G.; Diamond, H.; Vandegrift, G.
F.; Schultz, W. W. Solvent Extr. Ion Exch. 1985, 3, 75-109. (b)
Chamberlain, D. B.; Leonard, R. A.; Hoh, J. C.; Gay, E. C.; Kalina, D.
G.; Vandegrift, G. F. Truex Hot Demonstration: Final Report, Report
ANL-89/37, Argonne, IL, April 1990.
† Abteilung Lehramt Chemie, J. G.-Universita¨t Mainz.
‡ Permanent address: Institute of Organic Chemistry, NAS of
Ukraine, Murmanska str. 5, Kyiv-94, 02094, Ukraine.
§ Institut fu¨r Organische Chemie, J. G.-Universita¨t Mainz.
| Coordination and Radiochemistry, University of Lie`ge.
Institut de Chimie, Universite´ Louis Pasteur.
10.1021/jo050717a CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/25/2005
J. Org. Chem. 2005, 70, 6027-6033
6027

Rudzevich et al.
CHART 1
SCHEME 1. Synthesis of the Triphenylmethane
4aa
the four CMPO functions (Chart 1). In addition, there is
a pronounced selectivity for Am over Eu when extracted
from acidic media, as well as within the lanthanide series
for the lighter over the heavier elements. Rigidification
of the calix[4]arene skeleton surprisingly does not change
the selectivity, but increases further the extraction
ability.5
a
Reagents and conditions: (i) H2SO4, 155 °C; (ii) All-Br, K2CO3,
acetone, reflux; (iii) H2, Raney Ni, THF/EtOH; (iv) 8, NEt3 (cat),
CHCl3.
SCHEME 2. Synthesis of the Triphenylmethane
4ba
Early studies from Horwitz et al.2 indicated that three
CMPO molecules are coordinated to the trivalent actinide
cation strongly via their PdO and more weakly via their
CdO functions in a complex which contains additionally
three nitrate anions and three HNO3 molecules loosely
bound to the CdO groups. Consequently, a tripodal
arrangement of three CMPO groups should lead to an
even better ligand. Thus, trihydroxytriphenylmethane
was proposed as a scaffold6 on which three CMPO groups
were bound (3) similarly to compounds 2. Single-crystal
X-ray structures of lanthanide complexes showed the
expected coordination of 3.6 However, although high
extraction percentages were found for Th4+ the extraction
of trivalent cations (lanthanides) was less effective than
with 2. Since subtle differences in the mutual arrange-
ment/orientation of the CMPO groups might have a
crucial influence, we decided to study the tri-CMPO
derivatives 4, which are based again on trihydroxytri-
phenylmethane, but have (in contrast to 3) the CMPO
functions attached to the aromatic moieties as in the wide
rim derivatives 1.
a Reagents and conditions: (i) H2SO4, 105 °C; (ii) C5H11-Br,
K2CO3, CH3CN, reflux; (iii) HNO3, CH2Cl2; (iv) H2, Raney Ni, THF/
EtOH; (v) 8, NEt3 (cat), CHCl3.
by the active ester 8. While the yield of 7a (40% after
column chromatography) leaves room for improvement,
85% of 4a was obtained in the last step.
An alternative reaction sequence, exemplified in Scheme
2, allows (alkyl) substituents ortho to the alkoxy groups.
The triphenylmethane 10 was obtained by acid-catalyzed
condensation in formal analogy to 5, however, under
much milder conditions. Due to the higher nucleophilic-
ity, a complete O-alkylation is possible by simple alkyl-
bromides, e.g., pentyl bromide (K2CO3, acetonitrile, re-
flux, 80% of 11). The subsequent ipso-nitration (82% of
6b) and reduction (72% of 7b) followed procedures
described for calixarenes.8 The final N-acylation by 8
furnished 4b in 86% yield.
Results and Discussion
Synthesis. The parent compound 4a, unsubstituted
in the ortho positions relative to the alkoxy groups, was
obtained as shown in Scheme 1. Acid-catalyzed conden-
sation of 2-hydroxy-5-nitrobenzaldehyde with an excess
of p-nitrophenol led to the triphenylmethane 5 in nearly
90% yield. Since p-nitrophenol units are less reactive (less
nucleophilic) than alkylphenols we chose allyl bromide
for the etherification in the presence of K2CO3 (92% of
6a). Subsequent exhaustive hydrogenation gave the
propyl ether 7a7 in one step which was acylated as usual
All compounds were characterized by 1H and 13C NMR
spectra, which reflect their (dynamic) C3v symmetry, and
by FD mass spectra. In addition, the structures of 5 and
6a (Figure S3, Supporting Information) were confirmed
by single-crystal X-ray analysis. Both molecules assume
a conformation resembling a three bladed propeller with
a syn-orientation of the oxygen functions (OH, O-allyl)
and nitro groups. Angles between least-squares planes
through the aromatic rings are 88.9° for 5, which lies on
a 3-fold axis and 84.8, 82.6, and 82.3° for 6a. Intramo-
lecular distances for oxygen and nitrogen are O‚‚‚O 4.10
(3) Arnaud-Neu, F.; Bo¨hmer, V.; Dozol, J.-F.; Gru¨ttner, C.; Jakobi,
R. A.; Kraft, D.; Mauprivez, O.; Rouquette, H.; Schwing-Weill, M.-J.;
Simon, N.; Vogt, W. J. Chem. Soc., Perkin Trans. 2 1996, 1175-1182.
(4) Barboso, S.; Carrera, A. G.; Matthews, S. E.; Arnaud-Neu, F.;
Bo¨hmer, V.; Dozol, J.-F.; Rouquette, H.; Schwing-Weill, M.-J. J. Chem.
Soc., Perkin Trans. 2 1999, 719-723.
(5) Arduini, A.; Bo¨hmer, V.; Delmau, L.; Desreux, J.-F.; Dozol, J.-
F.; Carrera, M. A. G.; Lambert, B.; Musigmann, C.; Pochini, A.;
Shivanyuk, A.; Ugozzoli, F. Chem. Eur. J. 2000, 6, 2135-2144.
(6) Peters, M. W.; Werner, E. J.; Scott, M. Inorg. Chem. 2002, 41,
1707-1716.
(7) Rudzevich, Y.; Rudzevich, V.; Schollmeyer, D.; Thondorf, I.;
Bo¨hmer, V. Org. Lett. 2005, 7, 613-616.
(8) Jakobi, R. A.; Bo¨hmer, V.; Gru¨ttner, C.; Kraft, D.; Vogt, W. New
J. Chem. 1996, 20, 493-498.
6028 J. Org. Chem., Vol. 70, No. 15, 2005

Carbamoylmethylphosphinoxide Derivatives
than the Eu-O(C) ones, indicating a stronger coordina-
tion of the more basic phosphine oxide groups as observed
by crystallography in the case of a lanthanide CMPO
complex.5 The helical arrangement of ligand 4 around the
metal is reflected by gauche O-P-C-C and O-C-C-P
torsion angles as reported in Table 1. The [Eu(H2O)‚4]3+
and [Eu(NO3)‚4]2+ complexes with maximum CNs of
seven and eight, respectively, were also optimized to
assess whether ligand 4 can retain its coordination to
Eu3+ in the presence of either monodentate (H2O) or
bidentate (nitrate) ligands. The calculations show that
the [Eu‚4]3+ complex has a high affinity for H2O and
-
NO3 (-17 and -280 kcal/mol, respectively, at the DFT
level). The coordination of these groups leads to some
weakening and lengthening of the Eu-O bonds (∼ 0.05
and 0.1 Å, respectively) but has little influence on the
geometry of the ligand. The nitrate ion and the water
molecule are located close to the 3-fold axis and the
geometry of the trityl unit and of the amide groups
remains unchanged. However, the coordination sphere
of the Eu3+ ion is somewhat flattened (about 0.15 Å) by
-
the NO3 and H2O moieties.
FIGURE 1. Calculated structure of the Eu3+‚4 complex.
Ligand 4a is thus firmly coordinated to trivalent
lanthanide cations and the arrangement of its substitu-
ents is well adapted to forming stable 1:1 inclusion
complexes. The encapsulation of paramagnetic lan-
thanide ions in anhydrous acetonitrile is readily observed
by NMR spectroscopy and by nuclear magnetic relaxation
dispersion (NMRD). These two techniques were used
previously to unravel the properties of various calix[4]-
arenes featuring CMPO groups.12,13 Spectroscopy yields
information on the solution structure of a complex
because the induced paramagnetic shifts directly depend
on simple geometric factors. On the other hand, NMRD
allows one to investigate complexation and association
processes in solution. Figure 2 presents NMRD titration
curves of Gd(ClO4)3 by a calix[4]arene with four amide
groups12,13 on the narrow rim and by ligands 1, 4a, and
4b in anhydrous acetonitrile. The formation of a complex
is accompanied by a decrease in the longitudinal relax-
ation rate 1/T1 of the solvent molecules (relaxivity, in s-1
mmol-1) when a ligand is added to Gd3+ because resonat-
ing nuclei are removed from the first coordination sphere
of the paramagnetic ions and are thus allowed to relax
much more slowly. A linear relaxivity decrease followed
by a plateau for a 1:1 metal:ligand concentration ratio is
observed for a very stable complex. Figure 2 illustrates
the case of a calix[4]arene tetraamide that obviously
forms a highly stable 1:1 complex.12 By contrast, the
relaxivity can increase rather than decrease upon addi-
tion of a ligand if slowly rotating large polymeric species
are formed in solution as already reported for the Gd3+
complex with 1. The relaxivity of Gd3+ mixtures with 4a
and 4b in anhydrous acetonitrile have been measured
up to the solubility limit. A plateau is not yet reached in
these conditions but the relaxivities are very close to the
value obtained for the calix[4]arene tetraamide for which
only one acetonitrile molecule is coordinated to the metal
Å, N‚‚‚N 6.89 Å for 5 and between O‚‚‚O 3.61-4.01 Å,
N‚‚‚N 6.60-7.00 Å for 6a.
Molecular Simulation and Solution Properties.
In contrast with their transition-metal analogues, the
lanthanide ions have no stereochemical requirements and
the conformation of their complexes depends essentially
on the ligand properties. No crystal of diffraction quality
of the metal trityl-CMPO complexes could be obtained,
and it was thus decided to generate structures by
quantum mechanics and to study the solution behavior
of the complexes by nuclear magnetic resonance tech-
niques. Although a complete encapsulation of the lan-
thanides by ligand 4a was expected,6 the possibility
remained that the location of the substituents on the
trityl platform was not suitable for complexing these
metal ions. Moreover, solid state structures are known
in which carbamoylmethylphosphonate units are linked
to lanthanide ions either by the two donor groups or only
by the PdO function.6,10,11
Ab initio QM modeling studies were first undertaken
at the HF and DFT levels on the Eu(III) trityl-CMPO,
[Eu‚4]3+, in which the maximum coordination number
(CN) was fixed to six, i.e., less than the common CN of
eight or nine. For computing time saving purposes, the
P(Ph)2 groups of 4a were replaced by P(Me)2 moieties.
As shown in Figure 1, the metal is coordinated to all the
oxygenated binding sites of the ligand and the complex
features an approximate 3-fold symmetry. The main
Eu-O-optimized distances of the complexes are pre-
sented in Table 1.
The DFT results are a priori more accurate as electron
correlation effects are somewhat better taken into ac-
count. The Eu-O(P) distances are somewhat shorter
(9) Cambridge Crystallographic Data Centre, Cambridge, CB2 1EZ,
U.K.
(12) Lambert, B.; Jacques, V.; Shivanyuk, A.; Matthews, S. E.;
Tunayr, A.; Baaden, M.; Wipff, G.; Bo¨hmer, V.; Desreux, J. F. Inorg.
Chem. 2000, 39, 2033-2041.
(13) Schmidt, C.; Saadioui, M.; Bo¨hmer, V.; Host, V.; Spirlet, M. R.;
Desreux, J. F.; Brisach, F.; Arnaud-Neu, F. Dozol, J.-F. Org. Biol.
Chem. 2003, 1, 4089-4096.
(10) Gru¨ner, B.; Plesˇek, J.; Ba´cˇa, J.; Cisarˇova´, I.; Dozol, J. F.;
Rouquette, H.; Vinˇas, C.; Selucky´, P.; Rais, J. New. J. Chem. 2002,
26, 1519-1527.
(11) Caudle, L. J.; Duesler, E. N.; Paine, R. T. Inorg. Chem. 1985,
24, 4441-4444.
J. Org. Chem, Vol. 70, No. 15, 2005 6029

Rudzevich et al.
TABLE 1. Main Characteristics of Ln3+ Complexesa with CMPO Derivatives Obtained from QM Calculations (Top) and
Retrieved in the Crystallographic Structural Database9
QM optimized structures
CN
method
Eu-OP
Eu-OC
Eu-Owat
Eu-Onit
æ1
æ2
Eu3+‚4
6
6
7
7
8
8
HF
DFT
HF
DFT
HF
DFT
2.33
2.32
2.38
2.39
2.42
2.41
2.40
2.36
2.45
2.39
2.51
2.47
-
-
30
39
45
50
61
63
44
39
49
45
42
41
Eu3+‚4
-
-
Eu(H2O)3+‚4
Eu(H2O)3+‚4
Eu(NO3)2+‚4
Eu(NO3)2+‚4
2.52
2.54
-
-
-
-
2.49
2.46
X-ray structures6,10,11
CN
“REFCODE”
Ln-OP
Ln-OC
Ln-Owat
Ln-Onit
æ1
æ2
Nd(NO3)2+‚3 6
8
9
XILKAE A
XILKAE B
MUMDED
DODVAT
2.42
2.43
2.49
2.46
2.39
2.47
2.52
2.49
-
2.54
2.62
-
60
51
39
63
41
44
46
44
Nd(NO3)2+(H2O)‚1 6
La(H2O)33+‚CMPO-dicarbolide3
2.52
2.58
-
10
9
11
Nd(NO3)3‚CMPO2
10
2.60
a Eu-O distances (in Å) and torsional angles (in deg) æ1 (O-P-C-C) and æ2 (O-C-C-P) are averaged over the different CMPOs.
equilibria between different forms. The NMR spectrum
of [Yb‚4a]3+ as a perchlorate salt in anhydrous acetoni-
trile at room temperature features relatively narrow
peaks that cover about 35 ppm with paramagnetic shifts
both toward high and low fields (see the Supporting
Information). All resonances become exceedingly broad
when the temperature is decreased down to the freezing
point of the solvent. A complete assignment of the
resonances observed at room temperature is limited by
the inability to resolve closely overlapped peaks between
0 and 5 ppm. However, there are a few well-resolved
resonances between 7 and 12 ppm and at -4 ppm.
Moreover, one resonance at -20 ppm and of relative area
one is much more shifted than all other peaks and stands
out for special notice. The polar coordinates of each
FIGURE 2. Nuclear magnetic relaxation dispersion titration
proton have been deduced from the structure reported
curves. Gd(ClO4)3 in anhydrous acetonitrile titrated with .:
in Figure 1 for the Eu3+‚4a complex and a linear fit
1,12 2: 4a, b: 4b, ~: 5,11,17,23-Tetra-tert-butyl-25,26,27,28-
between the paramagnetic shifts and the geometric
factors yielded the magnetic susceptibility term D (see
the Supporting Information). These calculations showed
that the aromatic proton in ortho position relative to the
central methine group resonates at -20 ppm while all
other protons give rise to peaks between -2 and 12 ppm
in keeping with the observed spectrum. It is thus
concluded that the monomeric 1:1 [Yb‚4a]3+ complex is
probably the main solution species but a more detailed
analysis appears difficult.
tetrakis(N,N-diethylaminocarbonyl) methoxycalix[4]arene12
ion.12,14 No quantitative interpretation of the relaxivity
titration curves of 4a and 4b could be made on the basis
of a simple 1:1 equilibrium even if the relaxivity of the
complex was included in the fit in addition to the stability
constant. A 1:1 complex is most probably formed but
other species are certainly present in solution. The same
conclusion was reached with calix[4]arene featuring
CMPO groups on the wide rim.12
Paramagnetic lanthanide complexes of 3-fold sym-
metry such as those presumably formed by ligands 4a
and 4b are particularly interesting because their solution
structure can be directly deduced from the simplest form
of the dipolar equation
Extraction Data. The reprocessing of nuclear wastes
is currently performed by extracting selectively metal
ions from concentrated HNO3 aqueous solutions (1-3 M).
(Diisobutylcarbamoyl)methyloctylphenylphosphine oxide
(CMPO) is a relatively ineffective extractant and does not
allow an easy separation of Am(III) from Eu(III).15 Much
higher distribution coefficients of the trivalent lan-
thanides and actinides and much better Am(III)/Eu(III)
separation factors (about 10) are obtained if four CMPO
units are grafted on the wide rim of calix[4]arene, 1, as
shown in Figure 3. Extraction studies were performed
in hope that the trityl derivatives 4a and 4b would
feature the same interesting properties. Figure 3 presents
the acid dependency of the extraction coefficients of
Am(III) and Eu(III) by 4a in dichloromethane. Very simi-
lar results were obtained in the case of 4b. In contrast
3 cos2 θi - 1
δi ) D
(1)
ri3
that links the induced paramagnetic shift δi to the polar
coordinates θi and ri of nucleus i relative to the C3 axis
and to a magnetic susceptibility factor D which is
identical for all nuclei in a complex. However, this
equation is only valid if a single rigid species exists in
solution.12 NMRD indicates that this condition is not
fulfilled and only qualitative information can then be
obtained from spectra that result from rapid dynamic
(15) Delmau, L. H.; Simon, N.; Schwing-Weill, M. J.; Arnaud-Neu,
F.; Dozol, J. F.; Eymard, S.; Tournois, B.; Bo¨hmer, V.; Gru¨ttner, C.;
Musigmann, C.; Tunayar, A. J. Chem. Soc., Chem Commun. 1998,
1627-1628.
(14) Lambert, B.; Jacques, V.; Desreux, J. F. Adv. Chem. Ser. 2000,
757, 165-178.
6030 J. Org. Chem., Vol. 70, No. 15, 2005

Carbamoylmethylphosphinoxide Derivatives
FIGURE 3. Acid dependency of the extraction coefficients of Am3+ and Eu3+. Left: extraction by tripodal ligand 4a; right:
extraction by tetrapodal ligand 1 (b: Am3+; 9: Eu3+).
with calix[4]arene 1, the extraction efficiency of trityl 4a
drastically decreases when nitric acid is added to a 4 M
NaNO3 aqueous phase and it slightly increases at high
acidities. A selectivity DAm/DEu of about 2 is observed over
the whole range of nitric acid concentrations.
The trivalent f elements are extracted as neutral
adducts between the trinitrate salts and the ligand.16 As
observed with many CMPO derivatives, the extraction
coefficients of 1 increase up to 1 M HNO3 because the
larger concentration of nitrate ions favors the formation
of adducts. At higher acidities, the competition between
the protons and the metal ions for the complexation sites
brings about a decrease in extraction. The position of the
extraction maximum depends essentially on the basicity
of the phosphine oxide groups.16
The extraction of acid by 1 mM solutions of 1 and 4a
in dichloromethane was analyzed by titrating the organic
phases after equilibration with equal volumes of 2 M
HNO3/4 M NaNO3 aqueous phases. Under these condi-
tions, the organic phases containing 1 and 4a were,
respectively, 1.41 and 1.11 mM in HNO3. Furthermore,
the addition of NaNO3 to a 0.1 M HNO3 aqueous phase
only brings about a regular increase of the distribution
coefficients of Eu(III) and Am(III) (for a 1 mM dichlo-
romethane solution of 4a from 0.03 and 0.07 to 110 and
190 respectively when the concentration of NaNO3 is
increased to 5 M). The same tendency is observed with
all CMPO-containing compounds and 4a is not different
in this respect.
from the atmosphere whether as a solid or dissolved in
an organic solvent.
Conclusions
Since their extraction results are sensitive to acidity,
extractants 4a and 4b are of little practical interest.
However, these ligands illustrate the difficulties encoun-
tered when designing a priori ligands featuring scaffolds
that seem particularly well suited for extracting metal
ions. Ligand 1 with eight donor groups appears ideal for
the complexation of lanthanide ions that are well-known
to favor large coordination numbers. This ligand is indeed
a very effective extracting agent of the f elements but its
solution behavior is not as simple as anticipated5,12 and
the origin of its selectivity remains uncertain. The trityl-
CMPO ligands 4a and 4b also appeared as interesting
extracting agents before they were synthesized but their
sensitivity to acidity turned out to be detrimental. At first
glance, extraction processes seem very simple but they
are in fact quite complex as they depend on a number of
poorly defined parameters. According to small angle
neutron diffraction studies, CMPO and extracted lan-
thanide complexes form large elongated polymers of
17-40 Å in diameter and up to 500 Å long, the size of
which decreases if an excess of ligands is added.18 What
happens with grafted CMPOs remains to be investigated.
The assembly of several ligating functions on a com-
mon platform and the rigidifying effect of cyclic structures
often leads to improved efficiencies as demonstrated
many times by calixarene derived ligands. However,
because of the complex nature of the extraction process
selecting and developing new extractants still remains
essentially a trial and error process, as shown by the
present results.
The extracted amount of nitric acid reported above
corresponds to a protonation of 35-37% of the CMPO
functions for both compounds 1 as well as 4a. The
dramatic decrease of the distribution coefficients in the
latter case may be understood therefore, assuming that
all three ligating CMPO arms are necessary for the
complexation of a metal cation in the case of 4a in
addition to nitrate ions. All four CMPO functions of 1
are not necessarily required in the first coordination
sphere of the extracted metal ions as shown by the solid-
Experimental Section
Tris(2-hydroxy-5-nitrophenyl)methane (5). A mixture
of 5-nitrosalicylaldehyde (5.20 g, 0.031 mol) and p-nitrophenol
(26.0 g, 0.187 mol) was stirred with a mechanical stirrer at
110 °C under nitrogen until a homogeneous dark yellow melt
was formed. After that, sulfuric acid (4 mL) was added, the
temperature was increased to 155 °C, and stirring of the dark
brown viscous mass was continued for 2 h. To remove the
excess of p-nitrophenol the reaction mixture was extracted first
with hot water (3 × 150 mL). The remaining dark-brown
17
state structure of La2(NO3)6‚12 and by NMR studies.12
This would mean that the “better preorganization”
intended by the design of 4 is disadvantegous under the
envisaged extraction conditions. It is noteworthy in this
connection that 4a readily and reversibly picks up water
(16) Horwitz, E. P.; Martin, K. A.; Diamond, H.; Kaplan, L. Solvent
Extr. Ion Exch. 1986, 4, 449-494.
(17) Cherfa, S. Ph.D. Thesis, University of Paris, 1998.
(18) Diamond, H.; Thiyagarajan, P.; Horwitz, E. P. Solvent Extr. Ion
Exch. 1990, 8, 503-513.
J. Org. Chem, Vol. 70, No. 15, 2005 6031

Rudzevich et al.
powder was dissolved in 5% aqueous sodium hydroxide (300
mL), and an insoluble black solid was filtered off. The yellow
brown solution was added dropwise with stirring to 3.5%
aqueous hydrochloric acid (700 mL). The precipitate was
filtered off and dried at 140 °C on the air to give compound 5
(11.9 g, 89%) as a brown powder. Crystals suitable for X-ray
diffraction were obtained by crystallization from acetone: mp
310-320 °C dec; 1H NMR (400 MHz, DMSO-d6) δ 6.16 (s, 1H),
7.04 (d, 3H, 3JHH ) 9 Hz), 7.53 (d, 3H, 4JHH ) 3 Hz), 8.12 (d ×
[{M - Ph2P(O)CH2C(O)}+] (calcd 1190.27); MS (ESI-TOF) m/z
calcd for C70H70N3NaO9P3 1212.4217 (M + Na)+, found
1212.4196.
5-tert-Butyl-2-hydroxy-3-methylbenzaldehyde (9). A
mixture containing 4-tert-butyl-2-methylphenol (50 g, 0.304
mol), hexamethylenetetramine (HTM) (85.4 g, 0.609 mol), and
acetic acid (150 mL) was stirred at 130 °C for 3 h under
nitrogen. After cooling to 70 °C, aqueous sulfuric acid (33%,
150 mL) was added, and stirring was continued at 100 °C for
1 h. The resulting mixture was finally extracted with diethyl
ether (5 × 80 mL), and the extract was washed with water (5
× 80 mL) and dried (MgSO4). The solvent was removed under
reduced pressure to yield a dark yellow oil still containing
acetic acid. The crude product was purified by column chro-
matography (chloroform) to yield 9 (30.0 g, 51%) as a yellow
3
4
d, 3H, JHH ) 9 Hz, JHH ) 3 Hz); 13C{1H} NMR (100.6 MHz,
DMSO-d6) δ 37.8 (s), 115.5 (s), 124.5 (s), 124.9 (s), 128.7 (s),
139.4 (s), 161.5 (s); MS (FD) m/z 427.6 (100) [M+] (calcd
427.33).
Tris(2-allyloxy-5-nitrophenyl)methane (6a). Potassium
carbonate (1.94 g, 14.0 mmol) and allyl bromide (2.26 g, 18.7
mmol) were added to a solution of compound 5 (1.0 g, 2.3 mmol)
in acetone (10 mL) under nitrogen. The reaction mixture was
stirred at 65 °C for 2 days. The precipitate was filtered off.
Acetone and the excess allyl bromide were removed under
reduced pressure. The residue was dissolved in chloroform and
washed with 5% aqueous potassium carbonate and water. The
organic layer was separated, dried (MgSO4), and evaporated
to yield compound 6a (1.18 g, 92%) as a brown powder.
Crystals suitable for X-ray diffraction were obtained by
1
oil which slowly crystallized: mp ) 43-45 °C; H NMR (400
4
MHz, CDCl3) δ 1.32 (s, 9H), 2.27 (s, 3H), 7.35 (d, 1H, JHH
)
4
2.4 Hz), 7.44 (d, 1H, JHH ) 2.4 Hz), 9.86 (s, 1H), 11.11 (s,
1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ 15.3 (s), 31.3 (s), 34.0
(s), 119.4 (s), 126.2 (s), 127.3 (s), 135.7 (s), 142.2 (s), 157.9 (s),
196.9 (s); MS (FD) m/z 192.4 (100) [M+] (calcd 192.26).
Tris(5-tert-butyl-2-hydroxy-3-methylphenyl)meth-
ane (10). A mixture of 9 (10.0 g, 0.052 mol) and 4-tert-butyl-
2-methylphenol (25.6 g, 0.156 mol) was stirred at 105 °C under
nitrogen until a homogeneous melt was formed. Sulfuric acid
(0.5 mL) was added, and stirring of the dark-red viscous
mass was continued for 2 h. The cooled reaction mixture
was treated with methanol (160 mL), and the precipitate
formed was filtered off and dried on the air to give compound
1
crystallization from acetone: mp 164-165 °C; H NMR (400
MHz, CDCl3) δ 4.56 (m, 6H), 5.18 (m, 6H), 5.77 (m, 3H), 6.39
3
4
(s, 1H), 6.94 (d, 3H, JHH ) 9 Hz), 7.73 (d, 3H, JHH ) 3 Hz),
8.20 (d × d, 3H, JHH ) 9 Hz, JHH ) 3 Hz); 13C{1H} NMR
(100.6 MHz, CDCl3) δ 39.6 (s), 69.4 (s), 111.6 (s), 117.9 (s),
125.1 (s), 125.3 (s), 130.4 (s), 131.4 (s), 141.4 (s), 160.8 (s); MS
(FD) m/z 547.9 (100) [M+] (calcd 547.53).
3
4
1
10 (23.5 g, 90%) as a white powder: mp 335-340 °C dec; H
NMR (400 MHz, DMSO-d6) δ 1.10 (s, 27H), 2.13 (s, 9H), 6.62
4
4
(s, 1H), 6.73 (d, 3H, JHH ) 2.4 Hz), 6.87 (d, 3H, JHH ) 2.4
Hz), 7.83 (s, 3H); 13C{1H} NMR (100.6 MHz, DMSO-d6) δ 17.0
(s), 31.2 (s), 33.4 (s), 35.9 (s), 123.1 (s), 124.4 (s), 124.5 (s), 130.5
(s), 139.9 (s), 149.9 (s); MS (FD) m/z 503.3 (100) [M+] (calcd
502.74).
Tris(2-propoxy-5-aminophenyl)methane (7a). Com-
pound 6a (1.10 g, 2.0 mmol) was dissolved in a mixture of THF
(30 mL) and ethanol (25 mL) and hydrogenated for 24 h at
room temperature in the presence of the Raney nickel. The
catalyst was filtered off and washed with THF, and the
combined organic layers were evaporated under reduced
pressure. The pure product 7a (0.35 g, 38%) was isolated by
column chromatography (THF/hexane 3:2) as a brown pow-
der: mp ) 182-184 °C; 1H NMR (400 MHz, CDCl3) δ 0.83 (t,
Tris(5-tert-butyl-2-pentoxy-3-methylphenyl)methane
(11). Potassium carbonate (11.6 g, 0.084 mol) and 1-bromopen-
tane (16.8 g, 0.111 mol) were added under nitrogen to a
solution of compound 10 (7.0 g, 0.014 mol) in acetonitrile (200
mL). The reaction mixture was stirred at 90 °C for 6 days.
After the mixture was diluted with chloroform (200 mL), the
potassium salts were filtered off and the solvents were
removed under reduced pressure. Crystallization of the yellow
residue from chloroform/methanol gave compound 11 (7.96 g,
80%) as white crystals: mp 90-92 °C; 1H NMR (400 MHz,
CDCl3) δ 0.88 (t, 9H, 3JHH ) 7 Hz), 1.15 (s, 27H), 1.28 (m, 12H),
3
9H, JHH ) 7 Hz), 1.57 (m, 6H), 3.11 (br s, 6H), 3.68 (t, 6H,
4
3JHH ) 7 Hz), 6.22 (d, 3H, JHH ) 2.8 Hz), 6.39 (d × d, 3H,
4
3
3JHH ) 9 Hz, JHH ) 2.8 Hz), 6.41 (s, 1H), 6.61 (d, JHH ) 9
Hz); 13C{1H} NMR (100.6 MHz, CDCl3) δ 10.4 (s), 22.8 (s), 36.9
(s), 70.7 (s), 113.0 (s), 113.6 (s), 117.7 (s), 134.5 (s), 139.2 (s),
150.1 (s); MS (FD) m/z 463.8 (100) [M+] (calcd 463.63).
Tris(2-propoxy-5-diphenylphosphorylacetamido-
phenyl)methane (4a). Triethylamine (0.4 mL) was added
to a solution of p-nitrophenyl (diphenylphosphoryl)acetate3
(0.98 g, 2.57 mmol) and amino compound 7a (0.34 g, 0.73
mmol) in chloroform (10 mL), and the reaction mixture was
stirred for 12 h at room temperature. After the addition of
chloroform (10 mL), the organic solution was washed with
10% aqueous potassium carbonate and water. After drying
(MgSO4), the chloroform was removed under reduced pressure
and the residue was precipitated from chloroform by diethyl
ether to give compound 4a (0.74 g, 85%) as a light brown
powder. The product obtained as described contains three
molecules of water per molecule of 4a (according to the 1H
NMR) which can be removed by drying in a vacuum (0.1
mm/Hg) at 110 °C. 1H NMR investigations in CDCl3 show
broad signals due to weak association: mp ) 146-150 °C; 1H
NMR (400 MHz, THF-d8) δ 0.75 (t, 9H, 3JHH ) 7 Hz), 1.47 (m,
6H), 3.41 (d, 6H, 2JPH ) 14 Hz), 3.65 (t, 6H, 3JHH ) 6 Hz), 6.43
3
1.66 (m, 6H), 2.22 (s, 9H), 3.40 (t, 6H, JHH ) 7 Hz), 6.63 (s,
4
4
1H), 6.84 (d, 3H, JHH ) 2.4 Hz), 6.95 (d, 3H, JHH ) 2.4 Hz);
13C{1H} NMR (100.6 MHz, CDCl3) δ 14.1 (s), 16.8 (s), 22.7 (s),
28.2 (s), 29.9 (s), 31.4 (s), 34.1 (s), 37.5 (s), 72.4 (s), 125.4 (s),
125.8 (s), 129.7 (s), 136.7 (s), 144.8 (s), 153.4 (s); MS (FD) m/z
713.8 (100) [M+] (calcd 713.15).
Tris(5-nitro-2-pentoxy-3-methylphenyl)methane (6b).
Nitric acid (8 mL) was slowly added to a solution of compound
11 (4.2 g, 5.9 mmol) in methylene chloride (100 mL) and acetic
acid (12 mL). After being stirred for 2 h, the reaction mixture
was washed with water and dried (MgSO4), and the solvents
were removed under reduced pressure. Crystallization of the
yellow residue from chloroform/methanol gave compound 6b
(3.30 g, 82%) as beige crystals: mp 167-169 °C; 1H NMR (400
MHz, CDCl3) δ 0.87 (t, 9H, 3JHH ) 6.6 Hz), 1.25 (m, 12H), 1.57
(m, 6H), 2.36 (s, 9H), 3.49 (t, 6H, 3JHH ) 6.6 Hz), 6.64 (s, 1H),
4
4
7.57 (d, 3H, JHH ) 2.8 Hz), 8.05 (d, 3H, JHH ) 2.8 Hz);
13C{1H} NMR (100.6 MHz, CDCl3) δ 14.0 (s), 17.1 (s), 22.5 (s),
27.9 (s), 29.7 (s), 38.7 (s), 73.3 (s), 122.8 (s), 126.4 (s), 133.0
(s), 136.9 (s), 143.4 (s), 161.1 (s); MS (FD) m/z 680.7 (100) [M+]
(calcd 679.82).
3
(s, 1H), 6.50 (br s, 3H), 6.62 (d, 3H, JHH ) 9 Hz), 7.39 (m,
18H), 7.73 (br d, 3H, 3JHH ) 9 Hz), 7.82 (m, 12H), 9.34 (s, 3H);
13C{1H} NMR (100.6 MHz, THF-d8) δ 10.8 (s), 23.6 (s), 38.0
(s), 41.0 (d, 1JPC ) 61.5 Hz), 70.5 (s), 112.1 (s), 119.4 (s), 121.9
2
3
(s), 129.1 (d, JPC ) 12.3 Hz), 132.0 (d, JPC ) 9.8 Hz), 132.2
Tris(5-amino-2-pentoxy-3-methylphenyl)methane (7b).
Compound 7b was prepared as described for 7a. The pure
product 7b (72%) was isolated by column chromatography
(ethyl acetate/hexane 1:1) as a brown powder: mp ) 207-
4
1
(d, JPC ) 1.9 Hz), 132.9 (s), 133.8 (s), 134.8 (d, JPC ) 100.9
Hz), 154.0 (s), 163.3 (d, 2JPC ) 5 Hz); 31P{1H} NMR (162 MHz,
THF-d8) δ 26.2 (s); MS (FD) m/z 1191.1 (73) [M+], 948.6 (100)
6032 J. Org. Chem., Vol. 70, No. 15, 2005

Carbamoylmethylphosphinoxide Derivatives
1
3
210 °C; H NMR (400 MHz, CDCl3) δ 0.87 (t, 9H, JHH ) 6.6
when brought into contact with organic materials. It is highly
advisable to use only small quantities of metal salts with
proper care. All materials were handled under argon in a
glovebox.
Hz), 1.27 (m, 12H), 1.62 (m, 6H), 2.14 (s, 9H), 3.21 (br s, 6H),
3
4
3.38 (t, 6H, JHH ) 6.6 Hz), 6.17 (d, 3H, JHH ) 2.8 Hz), 6.31
(d, 3H, 4JHH ) 2.8 Hz), 6.42 (s, 1H); 13C{1H} NMR (100.6 MHz,
CDCl3) δ 14.1 (s), 16.5 (s), 22.7 (s), 28.2 (s), 29.9 (s), 37.6 (s),
72.6 (s), 115.4 (s), 115.7 (s), 131.6 (s), 138.5 (s), 141.1 (s), 148.6
(s); MS (FD) m/z 590.4 (100) [M+] (calcd 589.87).
Methods/Quantum Mechanics (QM) Calculations. The
metal complexes were optimized without symmetry constraints
by quantum mechanical calculations at the Hartree-Fock (HF)
and DFT (B3LYP functional) levels of theory, using Gaussi-
an98 software.21 As f-orbitals do not play a major role in the
studied metal-ligand bonds,22 the 46 core and 4f electrons of
europium were described by quasi-relativistic effective core
potentials (ECP) of the Stuttgart group, enhanced by an
additional single f-function with an exponent of 0.591.23,24 For
the valence orbitals, the affiliated (7s6p5d)/[5s4p3d] basis set
was used, enhanced by an additional single f-function. For the
ligands we used the 6-31G* basis set.
Tris(5-diphenylphosphorylacetamido-2-pentoxy-3-me-
thylphenyl)methane (4b). Compound 4b was synthesized
as described for 4a and isolated as a light brown powder with
86% yield: mp ) 160-164 °C; H NMR (400 MHz, CDCl3) δ
0.85 (t, 9H, JHH ) 6.6 Hz), 1.24 (m, 12H), 1.58 (m, 6H), 2.02
1
3
(br s, 9H), 3.15-3.35 (br m, 12H), 6.58 (s, 1H), 6.63 (br s, 3H),
7.30-7.45 (m, 18H), 7.68 (m, 12H); 13C{1H} NMR (100.6 MHz,
CDCl3) δ 14.0 (s), 16.5 (s), 22.6 (s), 28.1 (s), 29.8 (s), 36.6 (s),
1
39.9 (d, JPC ) 61.4 Hz), 72.6 (s), 120.2 (s), 122.2 (br s), 128.6
2
3
(d, JPC ) 12.2 Hz), 130.9 (d, JPC ) 9.5 Hz), 131.6 (s), 131.8
1
Acknowledgment. Financial support by the Euro-
pean Commission (Contracts No. FIKW-CT-2000-00088
and No. FI6W-CT-2003-508854) and by the Deutsche
Forschungsgemeinschaft (SFB 625) are gratefully ac-
knowledged. R.D. and G.W. thank the CNRS IDRIS and
CINES for allocation of computing time. J.F.D. and D.B.
acknowledge the financial support of the Institut In-
teruniversitaire des Sciences nucle´aires of Belgium.
(d, JPC ) 101.9 Hz), 132.3 (s), 132.8 (s), 137.4 (s), 152.5 (s),
163.0 (br s); 31P{1H} NMR (162 MHz, CDCl3) δ 29.5 (br s); MS
(FD) m/z 1319.4 (3) [M + 3H+], 1075.5 (100) [M - Ph2P(O)-
CH2C(O) + H+], 833.0 [M - 2{Ph2P(O)CH2C(O)} + H+] (calcd
1316.52); MS (ESI-TOF) m/z calcd for C79H88N3NaO9P3
1338.5626 (M + Na)+, found 1338.5593.
Single-Crystal X-ray Diffraction. All intensity data were
collected on a Enraf Nonius CAD4 diffractometer with Cu KR
radiation (graphite monochromator) at -80 °C (5) or at room
temperature (6a). The structures were solved using SIR9219
and refined with SHELX97.20 All non-hydrogen atoms were
refined anisotropically with C-H hydrogen atoms generated
at idealized positions and refined as riding atoms with
individual isotropic displacement parameters. The refinement
converged at R1 ) 0.071 for 5 and R1 ) 0.055 for 6a. The
position of the second disordered solvent molecule in crystals
of 5 could not be clarified.
Extraction Studies. Aqueous solutions containing the
152-154Eu and 241Am nuclides in tracer amounts were equili-
brated at 25 °C with equal volumes of dichloromethane
solutions of ligands 1, 4a, and 4b. After phase separation, the
activities of the aqueous and organic solutions were deter-
mined with a Canberra Genie 2000 γ spectroscopy system. All
extraction experiments were performed in triplicate.
Supporting Information Available: General experimen-
tal procedures; 1H NMR spectrum of Yb(ClO4)3‚4a in anhy-
drous acetonitrile; correlation between the calculated and the
experimental paramagnetic shifts; crystallographic data for
compounds 5 (CCDC 268244) and 6a (CCDC 268245); Carte-
sian coordinates optimized by HF and DFT calculations;
selected 1H and 13C NMR spectra of newly synthesized
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO050717A
(21) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A.,
Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.;
Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo,
C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.;
Wong, M. W.; Andres, J. L. Gonzalez, C.; Head-Gordon, M.; Replogle,
E. S.; Pople, J. A. Gaussian 98, Revision A.5 ed.; Gaussian, Inc.:
Pittsburgh, PA, 1998.
Nuclear Magnetic Resonance Studies. The NMR spectra
were recorded under the conditions reported elsewhere.12
Relaxivities 1/T1 were measured between 0.01 and 80 MHz
with a relaxometer equipped with a 2 T permanent magnet.
Anhydrous Yb(ClO4)3 was prepared as reported previously.12
CAUTION: lanthanide perchlorates are potentially explosive
(19) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi. A.;
Burla, M. C.; Polidori, G.; Camalli, M. J. Appl. Crystallogr. 1994, 27,
435-436.
(20) (a) Sheldrick, G. M. SHELXS97. Program for the Crystal
Structure Solution. University of Go¨ttingen, Germany, 1997. (b)
Sheldrick, G. M. SHELXS97. Program for the Crystal Structure
Refinement. University of Go¨ttingen, Germany, 1997.
(22) Maron, L.; Eisenstein, O. J. Phys. Chem. A 2000, 104, 7140-
7143.
(23) Dolg, M.; Stoll, H.; Savin, A.; Preuss, H. Theor. Chim. Acta 1989,
75, 173-194.
(24) Dolg, M.; Stoll, H.; Savin, A.; Preuss, H. Theor. Chim. Acta 1993,
85, 441-450.
J. Org. Chem, Vol. 70, No. 15, 2005 6033