Synthesis and evaluation of lipophilic BTBP ligands for An/Ln separation in nuclear waste treatment: The effect of alkyl substitution on extraction properties and implications for ligand design

Article abstract of DOI:10.1002/ejoc.201101576

Four new 6,6′-bis(1,2,4-triazin-3-yl)-2,2′-bipyridine (BTBP) ligands, which contain either additional alkyl groups on the pyridine rings or seven-membered aliphatic rings attached to the triazine rings, have been synthesized, and the effects of the additional alkyl substitution in the 4- and 4′-positions of the pyridine rings on their extraction properties with Ln^III and An^III cations in simulated nuclear waste solutions have been studied. The speciation of ligand 13 with some trivalent lanthanide nitrates was elucidated by ¹H NMR spectroscopic titrations and ESI-MS. Although 13 formed both 1:1 and 1:2 complexes with La^III and Y^III, only 1:2 complexes were observed with Eu^III and Ce^III. Quite unexpectedly, both alkyl-substituted ligands 12 and 13 showed lower solubilities in certain diluents than the unsubstituted ligand CyMe₄-BTBP. Compared to CyMe₄-BTBP, alkyl-substitution was found to decrease the rates of metal-ion extraction of the ligands in both 1-octanol and cyclohexanone. A highly efficient (D_Am > 10) and selective (SF_Am/Eu > 90) extraction was observed for 12 and 13 in cyclohexanone and for 13 in 1-octanol in the presence of a phase-transfer agent. The implications of these results for the design of improved extractants for radioactive waste treatment are discussed.

Full text of DOI:10.1002/ejoc.201101576

FULL PAPER
DOI: 10.1002/ejoc.201101576
Synthesis and Evaluation of Lipophilic BTBP Ligands for An/Ln Separation in
Nuclear Waste Treatment: The Effect of Alkyl Substitution on Extraction
Properties and Implications for Ligand Design
Frank W. Lewis,*[a] Laurence M. Harwood,*[a] Michael J. Hudson,[a] Petr Distler,[b]
Jan John,[b] Karel Stamberg,[b] Ana Núñez,[c] Hitos Galán,[c] and Amparo G. Espartero[c]
Keywords: Actinides / Lanthanides / Nuclear waste / Extraction / N ligands
Four new 6,6Ј-bis(1,2,4-triazin-3-yl)-2,2Ј-bipyridine (BTBP)
ligands, which contain either additional alkyl groups on the
pyridine rings or seven-membered aliphatic rings attached
to the triazine rings, have been synthesized, and the effects
of the additional alkyl substitution in the 4- and 4Ј-positions
of the pyridine rings on their extraction properties with LnIII
and AnIII cations in simulated nuclear waste solutions have
been studied. The speciation of ligand 13 with some trivalent
lanthanide nitrates was elucidated by 1H NMR spectroscopic
titrations and ESI-MS. Although 13 formed both 1:1 and 1:2
complexes with LaIII and YIII, only 1:2 complexes were ob-
served with EuIII and CeIII. Quite unexpectedly, both alkyl-
substituted ligands 12 and 13 showed lower solubilities in
certain diluents than the unsubstituted ligand CyMe4-BTBP.
Compared to CyMe4-BTBP, alkyl-substitution was found to
decrease the rates of metal-ion extraction of the ligands in
both 1-octanol and cyclohexanone.
A highly efficient
(DAm Ͼ 10) and selective (SFAm/Eu Ͼ 90) extraction was ob-
served for 12 and 13 in cyclohexanone and for 13 in 1-octanol
in the presence of a phase-transfer agent. The implications
of these results for the design of improved extractants for ra-
dioactive waste treatment are discussed.
A large number of extractants has been proposed and
tested in recent years for their ability to extract actinides in
the presence of lanthanides from aqueous nitric acid solu-
tions produced during the PUREX reprocessing of nuclear
waste.[4] Most promising are the 2,6-bis(1,2,4-triazin-3-yl)-
pyridine (BTP)[5] and 6,6Ј-bis(1,2,4-triazin-3-yl)-2,2Ј-bipyr-
idine (BTBP)[6] ligands, and one of the latter family,
CyMe4-BTBP (1, Figure 1)[7,8] is the current benchmark li-
gand for the SANEX process. This has been demonstrated
on genuine waste-fuel solution.[9] The substituted aliphatic
rings in 1 are designed to confer solubility in solvents such
as 1-octanol, and the absence of benzylic hydrogen atoms
enhances the resistance of the ligands to radiolytic degrada-
tion caused by free-radical species.[10] Recently, it has been
shown that the extraction properties of ligands such as 1
can be improved considerably if the ligand is preorganized
Introduction
One of the major goals in the treatment of nuclear waste
from the PUREX process is the selective removal of the
radiotoxic minor actinides (Am and Cm) from the lantha-
nides in a solvent extraction process, known as the SANEX
process.[1] Once removed, the oxides of these elements may
be converted by high-energy neutrons (transmutation) into
less radiotoxic or nonradiotoxic elements, which enables
safer geological disposal of the remaining waste or they
may be used as fuel in their own right in the proposed Gen-
eration IV fast reactors.[2] This strategy, known as partition-
ing and transmutation, promises to reduce the environmen-
tal impact and ultimately increase the sustainability of nu-
clear energy.[3]
[a] Department of Chemistry, University of Reading,
Whiteknights, Reading RG6 6AD, UK
Fax: +44-118-378-6121
E-mail: f.lewis@reading.ac.uk
l.m.harwood@reading.ac.uk
[b] Department of Nuclear Chemistry, Czech Technical University
in Prague,
Brˇehová 7, 11519 Prague 1, Czech Republic
Fax: +420-222-317-626
E-mail: jan.john@fjfi.cvut.cz
[c] Centro de Investigaciones Energéticas, Medio Ambientales y
Tecnológicas (CIEMAT),
Avda. Complutense 40, 28040 Madrid, Spain
Fax: +34-913-460-837
E-mail: amparo.espartero@ciemat.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101576.
Figure 1. Structures of 1 and 2.
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F. W. Lewis, L. M. Harwood, et al.
FULL PAPER
for metal binding with a phenanthroline moiety, which
We also reasoned that a BTBP ligand that contained a
seven-membered aliphatic ring would have a higher solubil-
locks the ligand into the required cis conformation.[11]
The tert-butyl-substituted derivative 2[12] (Figure 1) pos- ity than 1 in suitable organic diluents. Consequently, we
sesses a higher solubility than 1 in suitable diluents such as pursued the synthesis of BTBPs 24 and 25 derived from
1-octanol and cyclohexanone,[13] although its solvent ex- the condensation of dicarbohydrazonamide 23[22] with the
traction kinetics are slower than those of 1. More recently, seven-membered ring diketones 17 and 22. α-Diketones
a symmetrical BTP ligand derived from camphor has 17[23–25] and 22[23,24,26] were synthesized according to litera-
shown both improved solubility and fast extraction kinetics ture procedures as shown in Schemes 2 and 3. The intramo-
compared to related BTP ligands.[14] However, this ligand lecular acyloin reaction of diesters 15[23b] and 20[27] with
is susceptible to precipitate formation in contact with nitric
acid solutions of high acidity. A high extractant solubility
is desirable for the treatment of waste solutions that contain
high concentrations of metal ions, such as those produced
in the PUREX process.[15] In this study, we have synthesized
and evaluated some lipophilic symmetrical BTBP ligands
based on 1, which contain either two additional alkyl
groups or seven-membered aliphatic rings, in order to deter-
mine the effects of these modifications on the solubilities
and extraction properties of the ligands, and our results are
reported herein.
Results and Discussion
Scheme 2.
Ligand Synthesis
The 4,4Ј-disubstituted BTBP ligands 12 and 13 were syn-
thesized using the methodology previously used to synthe-
size 1.[7,8] Oxidation of the 2,2Ј-bipyridines 3 and 4 with
hydrogen peroxide in acetic acid afforded the bis-N-oxides
5[16,17] and 6,[17,18] which were converted into the dicar-
bonitriles 7[17,19] and 8[17] by a Reissert–Henze reaction with
trimethylsilyl cyanide and benzoyl chloride in CH2Cl2
(CAUTION: trimethylsilyl cyanide is a volatile hydrogen cy-
anide equivalent). The dicarbonitriles 7 and 8 were treated
with hydrazine hydrate in ethanol to generate the new dicar-
bohydrazonamides 9 and 10 in 81 and 79% yield, respec-
tively. Finally, the condensation of 9 and 10 with 3,3,6,6-
tetramethylcyclohexane-1,2-dione 11[20] (which was synthe-
sized by a modified procedure)[11,21] furnished the new 4,4Ј-
disubstituted BTBP ligands 12 and 13 (Scheme 1).
Scheme 3.
Scheme 1.
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Synthesis and Evaluation of Lipophilic BTBP Ligands for An/Ln Separation
sodium in the presence of chlorotrimethylsilane afforded NMR Spectroscopic Titrations with Lanthanide Salts
the enediolate bis-silyl ethers 16[23] and 21,[23] respectively.
NMR spectroscopic titrations of ligands with metal salts
These products were then oxidized to the corresponding α-
are a useful tool to probe the binding properties of ligands
diketones 17 and 22 with bromine in CCl4.
in solution and determine the stoichiometries of their com-
The condensation reaction of dicarbohydrazonamide 23
plexes.[30] The solution-phase speciation of 13 with some
with 17 and 22 failed to generate the corresponding BTBP
trivalent lanthanide nitrate salts was thus studied by 1H
ligands 24 and 25 in a range of different solvents [tetra-
NMR spectroscopic titrations in order to determine the
hydrofuran (THF), dioxane, EtOH, toluene, dibutyl ether,
stoichiometries of the complexes formed. The progressive
dimethyl sulfoxide (DMSO)] and starting materials were re-
addition of lanthanide nitrate salts (in CD3CN) in aliquots
covered in each case. Eventually, we found that the reac-
of 0.1 equiv. to a solution of 13 in CDCl3 led to the gradual
tions proceeded in pyridine after heating to reflux for 3 d
disappearance of the resonances from the free ligand and
(Scheme 4). We attribute the reduced reactivity of 17 and
the appearance of resonances that correspond to the metal
22 in these reactions to the differences in the O=C–C=O
complexes. Integration of a given resonance for each species
dihedral angles between these diketones and the more reac-
gives the relative amounts of the species present at different
tive six-membered ring diketone 11.[25b] Examination of the
metal/ligand ratios. In the case of lanthanum, both 1:1 and
1H NMR spectrum of the crude products showed the ex-
1:2 complexes were formed during the titration (see Sup-
pected resonances of the BTBPs in addition to at least one
porting Information). The 1:1 species was the major species
other product in each case, which could not be identified.
present at high metal/ligand ratios, whereas the 1:2 species
Unfortunately, all attempts to purify crude 24 and 25 failed
dominated if the metal/ligand ratio was 0.7 or less. How-
(recrystallization, chromatography, trituration) and, conse-
ever, even after 1.3 equiv. of metal were added, some 1:2
quently, pure samples of these ligands could not be ob-
complex still remained. In a previous study on BTP ligands,
tained for evaluation of their solvent extraction properties.
lanthanum complexes of 1:1, 1:2 and 1:3 stoichiometries
were found to be in equilibrium.[10] The normalized species
distribution curve for the titration of lanthanum with 13 is
presented in Figure 2. An enlargement of the aromatic re-
gion of the stack plot is shown in the Supporting Infor-
mation.
Scheme 4.
It is also known that the BTP and BTBP ligands extract
a number of fission products such as Mo, Zr, Ni, Pd and
Pb into the organic phase in addition to AmIII and
1
Figure 2. H NMR spectroscopic titration of 13 with La(NO3)3 in
CmIII [5g]
The presence of these metals in sufficiently high
.
CDCl3/CD3CN (᭿ free ligand, ᭹ 1:1 complex, ᭡ 1:2 complex).
concentrations can interfere with the extraction of AmIII by
sequestering the extractant. We therefore synthesized a PdII
In the titrations of 13 with europium and cerium nitrates,
complex of 13 using a previously reported procedure[28] in the progressive formation of only a single metal complex
order to characterize the type of species that could be in- was observed. Coordination of 13 to the paramagnetic EuIII
volved in the extraction of PdII. The 1:1 and 1:2 complexes ion caused a pronounced upfield shift to ca. 6.2 ppm of one
of related BTBPs with NiII have been reported pre- of the resonances for the aromatic protons. The disappear-
viously.[29] The 1:1 PdII complex of 13 was synthesized by ance of the free ligand resonances once 0.7 equiv. of euro-
treatment of 13 with Pd(OAc)2 in MeOH at reflux followed pium or 0.8 equiv. of cerium were added suggests that a 1:2
by anion metathesis with saturated methanolic ammonium complex was formed rather than a 1:1 complex. However,
1
hexafluorophosphate. The H NMR spectroscopic data for at a metal/ligand ratio of 0.5, the ratio of free ligand to
the complex were consistent with the formation of a single metal complex was close to 1:1 (Supporting Information).
symmetrical species. However, attempts to obtain crystals Assuming the formation of 1:2 complexes, the observation
suitable for X-ray diffraction were unsuccessful.
of free ligand resonances after 0.5 equiv. of metal were
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F. W. Lewis, L. M. Harwood, et al.
FULL PAPER
added indicates that the complexation reaction does not tribution patterns of the mass peaks were in excellent agree-
reach completion and is effectively driven to completion by ment with those calculated. Despite repeated attempts, ef-
the further addition of lanthanide salt. A stack plot for the forts to elucidate the crystal structures of the lanthanide
titration of 13 with Eu(NO3)3 is shown in Figure 3.
complexes of 13 by X-ray crystallography were unsuccess-
ful.
The data collected from the NMR spectroscopic ti-
trations of 13 with lanthanide nitrate salts were used to de-
velop a model for the complexation reactions from which
the preliminary stability constants of the complexes were
obtained (see Supporting Information for details).[32] The
preliminary calculated equilibrium stability constants for
the complexes formed between 13 and LaIII, YIII, EuIII and
CeIII are presented in Table 1.
Table 1. Calculated stability constants of the 1:1 (K1) and 1:2 (K2)
complexes of 13 with LnIII
.
LnIII
K1 [L/mol]
K2 [L/mol]
Ce
Eu
Y
n/a[a]
1.44ϫ1016 Ϯ2.08ϫ1015
1.42ϫ1016 Ϯ1.52ϫ1015
6.12ϫ1021 Ϯ2.48ϫ1021
6.12ϫ1021 Ϯ2.63ϫ1021
n/a[a]
6.12ϫ1013 Ϯ2.26ϫ1013
6.12ϫ1013 Ϯ2.32ϫ1013
Figure 3. NMR spectroscopic stack plot of the titration of 13 with
Eu(NO3)3. Bottom: spectrum of the free ligand. Each subsequent
spectrum corresponds to the addition of 0.1 equiv. of Eu(NO3)3.
La
[a] 1:1 complex not observed.
As was the case with lanthanum, both 1:1 and 1:2 species
were observed in the titration of 13 with yttrium (Figure 4).
However, in contrast to lanthanum, the 1:1 species is more
prevalent even at low metal/ligand ratios. Whereas the 1:1
complex of 13 with lanthanum became the major solution
species after the addition of 0.8 equiv. of metal salt, the 1:1
complex of 13 with yttrium was the major species present
after only 0.4 equiv. of metal salt were added. The bis com-
plex of 13 with yttrium was less able than that of lanthanum
to dissociate and form 1:1 complexes towards the end of
the titration, and the ratio of 1:1 and 1:2 complexes re-
mained largely unaltered despite the further addition of
metal salt. This may reflect the greater polarizing ability of
the YIII cation compared to LaIII. The stoichiometries of
the metal complexes formed at the end of the titrations of
13 with LaIII, EuIII and CeIII were verified by ESI-MS (Sup-
porting Information). Mass peaks were observed for the 1:2
complexes [M(13)2(NO3)]2+ in each case.[31] The isotope dis-
Solvent Extraction Properties
Ligands 12 and 13 were evaluated for their ability to ex-
tract and separate AmIII from EuIII from aqueous nitric
acid solutions into suitable organic diluents. The crude li-
gands 24 and 25 were not evaluated owing to the difficulties
encountered in their purification. The approximate solubili-
ties of 12 and 13 in these diluents were first determined and
are shown in Table 2. Quite unexpectedly, both 12 and 13
showed slightly lower solubilities than 1 and 2 in both 1-
octanol and cyclohexanone,[13] despite the presence of the
additional alkyl groups. A higher solubility of the ligands
was anticipated in these diluents. However, as shown by Ek-
berg et al., nonsymmetrical 2 possesses a far higher solubil-
ity than symmetrical 1 due to its higher entropy of dissol-
ution.[13] In symmetrical 12 and 13, this entropy effect will
be lost and results in a lower solubility than 2. It thus ap-
pears that alkyl substitution in a nonsymmetrical BTBP li-
gand such as 2 is the most promising method to increase
its solubility. Both 12 and 13 were more soluble in cyclo-
hexanone than 1-octanol, although paradoxically the solu-
bility of 12 was slightly higher than that of 13 in both of
these diluents. Neither ligand showed any appreciable solu-
bility in dodecane. For comparison purposes, 5 mm solu-
tions of each ligand in each of the diluents were used in the
initial extraction experiments (a concentration of 4.8 mm
was used for 13 in 1-octanol).
Table 2. Approximate solubilities [mm] of 12 and 13.
Diluent
12
13
1-Octanol
Cyclohexanone
3-Methylcyclohexanone 6–8
6–8
17–19
4.8–10
14–17
n.d.[a]
[a] Not determined.
The distribution ratios for AmIII and EuIII (DAm and
DEu) and the separation factors for americium over euro-
1
Figure 4. H NMR spectroscopic titration of 13 with Y(NO3)3 in
CDCl3/CD3CN (᭿ free ligand, ᭹ 1:1 complex, ᭡ 1:2 complex).
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Synthesis and Evaluation of Lipophilic BTBP Ligands for An/Ln Separation
pium (SFAm/Eu) for dimethyl-substituted 12 in 1-octanol as
a function of the nitric acid concentration of the aqueous
phase are shown in Figure 5. A reasonable selectivity was
observed for AmIII over EuIII, particularly at higher acidi-
ties (SFAm/Eu = 26 at 4 m HNO3). The D values for both
AmIII and EuIII increase with increasing nitric acid concen-
tration in the aqueous phase, in agreement with previous
studies on BTBP ligands. Similar results were observed for
the more lipophilic di-tert-butyl-substituted 13 in octanol
(Figure 6). A lower maximum separation factor was ob-
served in this case (SFAm/Eu = 14.8 at 4 m HNO3). For both
ligands the D values remained below 1, despite using a long
phase contact time of 6 h in each case. In contrast, D values
of up to 10 were observed for 1 in 1-octanol (10 mm) within
1 h of phase contact,[7] although a faster shaking device was
used in that case. As the extracted complexes formed by 12
Figure 6. Extraction of AmIII and EuIII as a function of [HNO3]
for 13 in 1-octanol (4.8 mm) at 25 °C, nonthermostatted
(᭡ DAm, ᭹ DEu, ᭿ SFAm/Eu, contact time: 6 h).
and 13 would be expected to be more lipophilic than those
formed by 1 or 2, we wondered if the lower D values ob-
served might be due to slower extraction kinetics.
Figure 7. Extraction of AmIII from 4 m HNO3 as a function of
contact time for 12, 13 and 1 in 1-octanol (5 mm for 12 and 1,
4.8 mm for 13) at 25 °C, nonthermostatted (᭿ = DAm for 12, ᭹ =
DAm for 13, ᭡ = DAm for 1).
Figure 5. Extraction of AmIII and EuIII as a function of [HNO3]
for 12 in 1-octanol (5 mm) at 25 °C, nonthermostatted (᭡ DAm
,
᭹ DEu, ᭿ SFAm/Eu, contact time: 6 h).
The extraction of AmIII and EuIII from 4 m HNO3 by 12 octyldiglycolamide (TODGA).[34] Using cyclohexanone as
and 13 in 1-octanol as a function of time was subsequently the diluent instead of 1-octanol also increases the rates of
investigated and compared with the corresponding data for extraction by BTBP ligands.[35] Therefore, we studied the
1. The dependence of the D value for AmIII on contact time extraction of AmIII and EuIII by 12 and 13 (5 mm solutions)
for 5 mm solutions of 1, 12 and 13 in 1-octanol is shown in as a function of [HNO3] using cyclohexanone as the dilu-
Figure 7. Both 12 and 13 suffer from slower extraction ki- ent. The results are presented in Figures 8 and 9 and show
netics than 1, and equilibrium was not reached even after that the choice of diluent strongly affects the extraction
30 h of contact time. Distribution ratios for AmIII greater properties of the ligands. For both ligands, there is a
than 1 were observed only after 30 h of contact for both marked improvement in both the extraction efficiency and
ligands, which confirms that slow extraction kinetics are re- Am/Eu selectivity in cyclohexanone compared to 1-octanol.
sponsible for the lower D values for 12 and 13 compared to When [HNO3] Ն 1 m, the D value for AmIII exceeds 10 and
1. Alkyl substitution of 1 at the 4- and 4Ј-positions of the SFAm/Eu is close to or exceeds 100. Although it is known
pyridine rings thus has a deleterious effect on the rates of that cyclohexanone participates to some extent in the non-
metal-ion extraction.
selective extraction of both metal ions, this effect is small
The kinetics of AmIII and EuIII extraction by BTBP li- and usually negligible.[36] It is possible that a synergistic ef-
gands in 1-octanol can be improved by using a phase-trans- fect takes place in the extraction by 12 and 13 in cyclohex-
fer agent such as 2-(hexyloxyethyl)-N,NЈ-dimethyl-N,NЈ-di- anone, which does not occur in 1-octanol. We briefly exam-
octylmalonamide (DMDOHEMA)[33] or N,N,NЈ,NЈ-tetra- ined the extraction properties of 12 in 3-methylcyclohex-
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F. W. Lewis, L. M. Harwood, et al.
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anone, a diluent we have investigated recently (see Support- straight line with a slope of 1.79 (for 12) and 2.01 (for 13),
ing Information),[36] but a detrimental effect on both the which confirms that 1:2 complexes were formed by both
extraction ability and the Am/Eu selectivity was observed ligands in agreement with previous studies on 1.[7]
in this diluent compared to cyclohexanone.
Figure 10. Extraction of AmIII from 2 m HNO3 as a function of
contact time for 12 and 13 in cyclohexanone (5 mm) at 25 °C, non-
thermostatted (᭿ DAm for 12, ᭹ DAm for 13).
Figure 8. Extraction of AmIII and EuIII as a function of [HNO3] for
12 in cyclohexanone (5 mm) at 25 °C, nonthermostatted (᭡ DAm
,
᭹ DEu, ᭿ SFAm/Eu, contact time: 6 h).
It is known that the presence of benzylic hydrogen atoms
in BTP and BTBP ligands leads to chemical attack at these
positions by free-radical species formed during exposure of
the organic and aqueous phases to radionuclides.[37] Fur-
ther studies on 12 were discontinued and 13 was chosen for
studies to improve the kinetics of extraction into 1-octanol,
which is the preferred diluent for process implementation.
The effect of the nitric acid concentration of the aqueous
phase on the distribution ratios of AmIII and EuIII and the
extraction kinetics was studied to determine the optimum
conditions for the extraction. The variation of the D values
with contact time at three different concentrations of nitric
acid (0.2, 1 and 3 m HNO3) show that the optimum extrac-
tion by 13 takes place from 3 m HNO3 after 90 min of con-
tact time (Supporting Information). In the extraction from
0.2 m HNO3, the D values for both metals remain below
0.1, which indicates that dilute nitric acid solutions would
be suitable for the back-extraction of both metals from the
loaded organic phase.
Figure 9. Extraction of AmIII and EuIII as a function of [HNO3] for
13 in cyclohexanone (5 mm) at 25 °C, nonthermostatted (᭡ DAm
,
᭹ DEu, ᭿ SFAm/Eu, contact time: 6 h).
The influence of DMDOHEMA and TODGA on the
extraction of AmIII and EuIII by 13 from 3 m HNO3 was
The variation of DAm with phase contact time for 12 and investigated in order to improve the slow extraction kinetics
13 in cyclohexanone is shown in Figure 10. As expected, the of 13. The extraction of AmIII and EuIII as a function of
use of cyclohexanone as the diluent led to a considerable contact time was studied at three different concentrations
improvement in the kinetics of extraction compared to 1- of DMDOHEMA (Figure 11). Progressively higher concen-
octanol. Equilibrium was reached within 30 min for 12 and trations of DMDOHEMA led to the improved extraction
within 2 h for 13. For 12, these extraction kinetics are com- of both metals, although equilibrium was not reached
parable to other BTBP ligands,[36] but for the more lipo- within 45 min of contact. The best results were observed in
philic 13, the extraction kinetics are still significantly slower the presence of 0.25 m DMDOHEMA, which improved the
than those of other BTBP ligands in cyclohexanone.[35] The kinetics of extraction such that a DAm value of 3.6 was ob-
relationship between the D values for AmIII in cyclohex- tained after 45 min of contact (this compares to DAm
=
anone and the ligand concentration was investigated to de- 0.959 after 45 min in the absence of DMDOHEMA). Sim-
termine the metal/ligand stoichiometry of the extracted ilar results were observed in the presence of TODGA (DAm
complexes. A plot of log(DAm) vs. log[BTBP] gave a = 3.63 after 45 min), although the extraction of EuIII was
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Synthesis and Evaluation of Lipophilic BTBP Ligands for An/Ln Separation
XXX400 instrument. Chemical shifts are reported in parts per mil-
significantly higher in this case and led to a reduction in
the Am/Eu separation factor (Supporting Information).
lion downfield from tetramethylsilane. Coupling constants (J) are
quoted in Hertz. Assignments were verified with 1H-1H and 1H-
13C COSY experiments as appropriate. Multiplicities and peak as-
signments are abbreviated as follows: singlet (s), doublet (d), triplet
(t), quartet (q), quintet (qu), multiplet (m), double doublet (dd),
double triplet (dt), double quartet (dq), broad (br.), apparent (app.)
and quaternary carbon (quat.). Mass spectra were obtained under
electrospray conditions with a Thermo Scientific LTQ Orbitrap XL
instrument. Elemental analyses were carried out by Medac Ltd.,
Chertsey Road, Chobham, Surrey, UK. Anhydrous diethyl ether
was dried and distilled from sodium benzophenone ketyl prior to
use. Diisopropylamine was dried and distilled from calcium hydride
prior to use. Toluene was dried with calcium chloride prior to use.
All organic reagents were obtained from either Acros or Aldrich,
whereas inorganic reagents were obtained from either BDH or Ald-
rich and used as received. 3,3,6,6-Tetramethylcyclohexane-1,2-di-
one (11) was synthesized by a previously described procedure.[11,21]
Synthesis of Bis-N-Oxides 5 and 6. General Procedure: The 4,4Ј-
disubstituted-2,2Ј-bipyridine 3 or 4 (9.00 g, 48.84 mmol for 3,
33.53 mmol for 4) was dissolved in acetic acid (50 mL) and hydro-
gen peroxide (27.66 mL for 3, 19.00 mL for 4, 30%, 5 equiv.) was
added dropwise. The solution was stirred at 100 °C for 4 h. The
solution was allowed to cool to room temperature, and hydrogen
peroxide (27.66 mL for 3, 19.00 mL for 4, 30%, 5 equiv.) was added
dropwise. The solution was stirred at 100 °C for 4 h. The solution
was allowed to cool to room temperature and stirring was contin-
ued for a further 24 h. Solid sodium hydrogen carbonate was added
until the solution became basic. The solution was extracted with
chloroform (3ϫ100 mL). The combined organic phases were dried
with sodium sulfate and evaporated to afford 5 or 6.
Figure 11. Extraction of AmIII and EuIII from 3 m HNO3 into 1-
octanol by 13 (5 mm) as a function of contact time at different
concentrations of DMDOHEMA (full symbols: DAm, empty sym-
bols: DEu, ᭿ D at 0.05 m DMDOHEMA, ᭡ D at 0.16 m
DMDOHEMA, ᭹ D at 0.25 m DMDOHEMA).
Conclusions
We have reported the synthesis, lanthanide speciation
and AmIII/EuIII solvent extraction properties of BTBP li-
gands that bear additional alkyl groups in the 4- and 4Ј-
positions of the pyridine rings of the parent ligand. A lower
reactivity was observed in the condensation reactions of
seven-membered ring α-diketones with a dicarbohydrazon-
amide compared to those of a six-membered ring α-diketone.
Paradoxically, the presence of the additional alkyl groups
does not increase the solubilities of the ligands and leads to
extraction kinetics that are considerably slower than those
found for unsubstituted BTBPs. However, the substituted
BTBPs are highly efficient and selective in the extraction
and separation of AmIII from EuIII both in cyclohexanone
and 1-octanol in the presence of a phase modifier. Thus
alkyl substitution of BTBP ligands does not necessarily im-
prove their solubilities, at least in the case of symmetrical
BTBPs. NMR spectroscopic titrations and MS studies
showed that the ligands formed both 1:1 and 1:2 complexes
with LaIII and YIII but only 1:2 complexes with EuIII and
CeIII. Preliminary stability constants of the LnIII complexes
were determined from NMR spectroscopic data. The chal-
lenge to increase the solubilities of the BTBP ligands with-
out adversely affecting their extraction kinetics thus re-
mains to be addressed.
4,4Ј-Dimethyl-2,2Ј-bipyridine 1,1Ј-Dioxide (5):[16,17] Yellow solid
1
(7.89 g, 74%). H NMR (400.1 MHz, CDCl3, Me4Si): δ = 8.27 (d,
J = 6.6 Hz, 2 H, 6-ArH and 6Ј-ArH), 7.51 (app. s, 2 H, 3-ArH and
3Ј-ArH), 7.17 (app. d, J = 6.6 Hz, 2 H, 5-ArH and 5Ј-ArH), 2.39
(s, 6 H, 4-CH3 and 4Ј-CH3) ppm. HRMS (CI): calcd. for
C12H13N2O2 [M + H]+ 217.0977; found 217.0965.
4,4Ј-Di-tert-butyl-2,2Ј-bipyridine 1,1Ј-Dioxide (6):[17,18] Yellow
1
foamy solid (9.72 g, 96%). H NMR (400.1 MHz, CDCl3, Me4Si):
δ = 8.25 (d, J = 8.0 Hz, 2 H, 6-ArH and 6Ј-ArH), 7.64 (d, J =
4.0 Hz, 2 H, 3-ArH and 3Ј-ArH), 7.33 (dd, J = 8.0 and 4.0 Hz, 2
H, 5-ArH and 5Ј-ArH), 1.35 (s, 18 H, 4-C(CH3)3 and 4Ј-C(CH3)3)
ppm. HRMS (CI): calcd. for C18H25N2O2 [M + H]+ 301.1916;
found 301.1918.
Synthesis of Dicarbonitriles 7 and 8. General Procedure: Bis-N-oxide
5 or 6 (7.89 g, 36.52 mmol for 5, 13.53 g, 45.10 mmol for 6) was
suspended in CH2Cl2 (130 mL for 5, 200 mL for 6) and trimethyl-
silyl cyanide (15.99 mL, 127.84 mmol for 5, 19.74 mL, 157.85 mmol
for 6, 3.5 equiv.) was added. Benzoyl chloride (14.84 mL,
127.84 mmol for 5, 18.32 mL, 157.85 mmol for 6, 3.5 equiv.) was
slowly added over 15 min, and the solution was stirred at room
temperature for 24 h and then heated under reflux for 2 d. The
solution was allowed to cool to room temperature and CH2Cl2
(100 mL) was added. The undissolved solid was collected by fil-
tration and washed with solvents [MeOH (15 mL) and ether
(15 mL) for 5, CH2Cl2 (20 mL) for 6] and allowed to dry in air to
afford 7 or 8 (0.49 g for 7, 8.11 g for 8). 10% Potassium carbonate
solution (150 mL) was added to the filtrate and the phases were
vigorously stirred for 15 min. The phases were separated and the
aqueous phase was extracted with CH2Cl2 (25 mL). The combined
organic phases were dried (MgSO4) and evaporated to yield a semi-
solid which was triturated with MeOH (100 mL), filtered and
Experimental Section
General Procedures: Melting points were obtained with a Stuart
SMP10 instrument. IR spectra were recorded as Nujol® mulls with
a Perkin–Elmer RX1 FTIR instrument. 1H and 13C{1H} NMR
spectra were recorded using either a Bruker AMX400 or an Avance
Eur. J. Org. Chem. 2012, 1509–1519
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1515

F. W. Lewis, L. M. Harwood, et al.
FULL PAPER
washed with MeOH (100 mL) and ether (50 mL) to yield 7 or 8
(3.83 g for 7, 1.97 g for 8).
lid was collected by filtration and washed with MeOH (80 mL) and
diethyl ether (40 mL) to afford 12 or 13.
4,4Ј-Dimethyl-2,2Ј-bipyridine-6,6Ј-dicarbonitrile (7):[17,19] Off-white
4,4Ј-Dimethyl-6,6Ј-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-
solid. Total yield: 4.32 g (50%). 1H NMR (400.1 MHz, CDCl3, benzotriazin-3-yl)-2,2Ј-bipyridine (12): Yellow solid (0.46 g, 49%);
Me4Si): δ = 8.52 (app. q, J = 0.7 Hz, 2 H, 3-ArH and 3Ј-ArH),
m.p. 286 °C (from MeOH). C34H42N8 (562.35): calcd. C 72.57, H
7.58 (app. q, J = 0.7 Hz, 2 H, 5-ArH and 5Ј-ArH), 2.54 (s, 6 H, 4- 7.52, N 19.90; found C 72.14, H 7.80, N 19.65. IR (Nujol): ν
=
˜
max
CH3 and 4Ј-CH3) ppm. HRMS (CI): calcd. for C14H11N4
2916, 1588, 1556, 1507, 1456, 1376, 1349, 1249, 1142, 1048, 1015,
[M + H]+ 235.0984; found 235.0979.
929, 867, 832, 717, 682 cm–1 1H NMR (400.1 MHz, CDCl3,
.
Me4Si): δ = 8.78 (app. q, J = 0.7 Hz, 2 H, 3-ArH and 3Ј-ArH),
8.32 (app. q, J = 0.7 Hz, 2 H, 5-ArH and 5Ј-ArH), 2.58 (s, 6 H, 4-
CH3 and 4Ј-CH3), 1.89 (s, 8 H, 4ϫCH2), 1.53 (s, 12 H, 4ϫCH3),
1.47 (s, 12 H, 4 ϫ CH3) ppm. 13C NMR (100.6 MHz, CDCl3,
Me4Si): δ = 164.2 (2ϫquat.), 162.9 (2ϫquat.), 161.0 (2ϫquat.),
156.0 (2ϫquat.), 152.6 (2ϫquat.), 149.1 (2ϫquat.), 124.8 (C-5
and C-5Ј), 123.7 (C-3 and C-3Ј), 37.2 (2ϫquat.), 36.4 (2ϫquat.),
33.8 (2ϫCH2), 33.3 (2ϫCH2), 29.7 (4ϫCH3), 29.2 (4ϫCH3), 21.5
(4-CH3 and 4Ј-CH3) ppm. HRMS (CI): calcd. for C34H43N8 [M +
H]+ 563.3605; found 563.3606.
4,4Ј-Di-tert-butyl-2,2Ј-bipyridine-6,6Ј-dicarbonitrile (8):[17] White
solid. Total yield: 10.08 g (70%). 1H NMR (400.1 MHz, CDCl3,
Me4Si): δ = 8.68 (d, J = 1.9 Hz, 2 H, 3-ArH and 3Ј-ArH), 7.75 (d,
J = 1.9 Hz, 2 H, 5-ArH and 5Ј-ArH), 1.42 (s, 18 H, 4-C(CH3)3 and
4Ј-C(CH3)3) ppm. HRMS (CI): calcd. for C20H23N4
[M + H]+ 319.1923; found 319.1926.
Synthesis of Dicarbohydrazonamides 9 and 10. General Procedure:
To a suspension of 7 or 8 (1.08 g, 4.61 mmol for 7, 10.08 g,
31.69 mmol for 8) in EtOH (80 mL for 7, 300 mL for 8) was added
hydrazine hydrate (30 mL, 64% for 7, 150 mL, 64% for 8). The
suspension was stirred at room temperature for 14 d. In the case of
8, the suspension was stirred at 60–70 °C for an additional 2 d to
give a clear solution. Water (400 mL for 7, 3 L for 8) was added,
and the precipitated solid was collected by filtration, washed with
water (150 mL for 7, 400 mL for 8) and allowed to dry in air over-
night to afford 9 or 10.
4,4Ј-Di-tert-butyl-6,6Ј-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-
1,2,4-benzotriazin-3-yl)-2,2Ј-bipyridine (13): Yellow solid (0.71 g,
21%); m.p. Ͼ300 °C (from MeOH). C40H54N8 (646.44): calcd. C
74.27, H 8.41, N 17.31; found C 73.92, H 8.43, N 17.01. IR (Nujol):
ν
max = 2921, 1591, 1550, 1510, 1456, 1376, 1346, 1260, 1161, 1099,
˜
1
1061, 894, 854, 720 cm–1. H NMR (400.1 MHz, CDCl3, Me4Si):
δ = 8.96 (d, J = 1.8 Hz, 2 H, 3-ArH and 3Ј-ArH), 8.65 (d, J =
1.8 Hz, 2 H, 5-ArH and 5Ј-ArH), 1.91 (s, 8 H, 4ϫCH2), 1.53 (s,
12 H, 4ϫCH3), 1.51 (s, 12 H, 4ϫCH3), 1.48 (s, 18 H, 4-C(CH3)3
and 4Ј-C(CH3)3) ppm. 13C NMR (100.6 MHz, CDCl3, Me4Si): δ =
164.7 (2 ϫ quat.), 162.7 (2 ϫ quat.), 162.0 (2 ϫ quat.), 161.6
(2ϫquat.), 156.4 (2ϫquat.), 152.6 (2ϫquat.), 121.1 (C-5 and C-
5Ј), 119.6 (C-3 and C-3Ј), 37.3 (2ϫquat.), 36.4 (2ϫquat.), 35.3 (4-
C(CH3)3 and 4Ј-C(CH3)3), 33.8 (2ϫCH2), 33.3 (2ϫCH2), 30.6 (4-
C(CH3)3 and 4Ј-C(CH3)3), 29.8 (4ϫCH3), 29.1 (4ϫCH3) ppm.
HRMS (CI): calcd. for C40H55N8 [M + H]+ 647.4544; found
647.4529.
4,4Ј-Dimethyl-2,2Ј-bipyridine-6,6Ј-dicarbohydrazonamide (9): White
solid (1.12 g, 81%); m.p. Ͼ300 °C (from H2O/EtOH). C14H18N8
(298.16): calcd. C 56.36, H 6.08, N 37.54; found C 55.97, H 5.74,
N 37.42. IR (Nujol): ν
= 3439 (NH2), 3346 (NH2), 2917, 1626,
˜
max
1591, 1454, 1374, 1231, 1160, 1026, 990, 869, 828, 779, 754 cm–1.
1H NMR (400.1 MHz, [D6]DMSO): δ = 8.44 (app. q, J = 0.7 Hz,
2 H, 3-ArH and 3Ј-ArH), 7.79 (app. q, J = 0.7 Hz, 2 H, 5-ArH
and 5Ј-ArH), 5.96 (br. s, 4 H, 2ϫNH2), 5.48 (br. s, 4 H, 2ϫNH2),
2.44 (s, 6 H, 4-CH3 and 4Ј-CH3) ppm. 13C NMR (100.6 MHz, [D6]-
DMSO): δ = 153.1 (2ϫquat.), 151.1 (2ϫquat.), 147.7 (2ϫquat.),
120.9 (C-3 and C-3Ј), 119.7 (C-5 and C-5Ј), 113.6
(2ϫH2NC=NNH2), 20.8 (4-CH3 and 4Ј-CH3) ppm. HRMS (CI):
calcd. for C14H19N8 [M + H]+ 299.1727; found 299.1725.
Diethyl 2,2,6,6-Tetramethylheptanedioate (15):[23b] Anhydrous di-
ethyl ether (240 mL) was placed in an oven-dried 500 mL three-
necked flask and sealed under an atmosphere of nitrogen. Diiso-
propylamine (34.6 mL, 246.87 mmol, 1.1 equiv.) was added by sy-
ringe and the solution was cooled to –20 °C. n-Butyllithium
(89.7 mL, 2.5 m, 224.43 mmol, 1 equiv.) was added dropwise by sy-
ringe and the solution was stirred at –20 °C for 15 min. Ethyl iso-
butyrate 14 (30.0 mL, 26.07 g, 224.43 mmol) was added dropwise
by syringe over 30 min, and the solution was warmed to room tem-
perature and stirred for an additional 1 h. 1,3-Diiodopropane
(12.88 mL, 112.21 mmol, 0.5 equiv.) was added dropwise over
15 min and the solution was heated under reflux for 24 h. The flask
was allowed to cool to room temperature, the solution was
quenched with saturated aqueous ammonium chloride solution
(150 mL) and the phases were mixed and separated. The aqueous
phase was extracted with diethyl ether (2ϫ50 mL). The combined
organic extracts were dried (MgSO4) and evaporated under reduced
pressure to afford a yellow liquid (42.95 g), which was purified by
vacuum distillation using a Vigreux column to afford 15 as a
colourless liquid (17.35 g, 56 %). B.p. 86–92 °C at 0.1 Torr. 1H
NMR (400.1 MHz, CDCl3, Me4Si): δ = 4.10 (q, J = 7.8 Hz, 4 H,
2ϫCO2CH2CH3), 1.46–1.50 (m, 4 H, 3-CH2 and 5-CH2), 1.23 (t,
J = 7.8 Hz, 6 H, 2ϫCO2CH2CH3), 1.17 (s, 2 H, 4-CH2), 1.14 (s,
12 H, 2ϫ2-CH3 and 2ϫ6-CH3) ppm.
4,4Ј-Di-tert-butyl-2,2Ј-bipyridine-6,6Ј-dicarbohydrazonamide (10):
Light brown solid (9.63 g, 79%); m.p. Ͼ300 °C (from H2O/EtOH).
C20H30N8 (382.25): calcd. C 62.80, H 7.90, N 29.28; found C 62.46,
H 7.51, N 28.83. IR (Nujol): νmax = 3438 (NH2), 3325 (NH2), 2916,
˜
1647, 1585, 1545, 1456, 1376, 1268, 1201, 1144, 1031, 994, 884, 725
cm–1. 1H NMR (400.1 MHz, [D6]DMSO): δ = 8.45 (d, J = 1.8 Hz,
2 H, 3-ArH and 3Ј-ArH), 7.99 (d, J = 1.8 Hz, 2 H, 5-ArH and 5Ј-
ArH), 5.88 (br. s, 4 H, 2ϫNH2), 5.38 (br. s, 4 H, 2ϫNH2), 1.37
(s, 18 H, 4-C(CH3)3 and 4Ј-C(CH3)3) ppm. 13C NMR (100.6 MHz,
[D6]DMSO):
δ = 160.4 (2ϫquat.), 153.6 (2ϫquat.), 151.4
(2ϫH2NC=NNH2), 143.4 (2ϫquat.), 117.2 (C-3 and C-3Ј), 115.7
(C-5 and C-5Ј), 34.8 (4-C(CH3)3 and 4Ј-C(CH3)3), 30.2 (4-C-
(CH3)3 and 4Ј-C(CH3)3) ppm. HRMS (CI): calcd. for C20H31N8
[M + H]+ 383.2666; found 383.2670.
Synthesis of BTBP Ligands 12 and 13. General Procedure: Dicar-
bohydrazonamide
9 or 10 (0.50 g, 1.67 mmol for 9, 2.00 g,
5.23 mmol for 10) was suspended in dioxane (50 mL for 9, 150 mL
for 10) and 11 (0.62 g, 3.69 mmol for 9, 1.93 g, 11.51 mmol for 10,
2.2 equiv.) was added. Triethylamine (5 mL for 9, 15 mL for 10)
was added and the suspension was heated under reflux for 3 d.
The suspension was allowed to cool to room temperature, and the
insoluble solid was filtered and washed with CH2Cl2 (10 mL). The
filtrate was evaporated under reduced pressure to afford a yellow
solid, which was triturated with MeOH (50 mL). The insoluble so-
3,3Ј-Thiobis(2,2-dimethylpropanoic Acid) (19):[26a,26b,27,38] Chloro-
pivalic acid 18 (50.37 g, 368.79 mmol) was suspended in water
(45 mL) and solid sodium carbonate (19.54 g, 184.39 mmol,
1516
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1509–1519

Synthesis and Evaluation of Lipophilic BTBP Ligands for An/Ln Separation
0.5 equiv.) was added. A solution of sodium sulfide nonahydrate
(400.1 MHz, CDCl3, Me4Si): δ = 1.71–1.77 (m, 2 H, 5-CH2), 1.64–
(44.28 g, 184.39 mmol, 0.5 equiv.) in water (35 mL) was added 1.68 (m, 4 H, 4-CH2 and 6-CH2), 1.15 (s, 12 H, 2ϫ3-CH3 and
dropwise over 10 min. The solution was stirred at 45–50 °C for
24 h. The flask was cooled to room temperature, and 50% aqueous
sulfuric acid (ca. 100 mL) was added in small aliquots with stirring.
The precipitated solid was collected by filtration, washed with
water (50 mL) and allowed to dry in air. The solid was dried at
2ϫ7-CH3) ppm.
3,3,6,6-Tetramethylthiepane-4,5-dione (22):[23,24,26] Yellow liquid
(12.06 g, 94%). B.p. 82–84 °C at 0.1 Torr. 1H NMR (400.1 MHz,
CDCl3, Me4Si): δ = 2.59 (s, 4 H, 2-CH2 and 7-CH2), 1.27 (s, 12 H,
2ϫ3-CH3 and 2ϫ6-CH3) ppm.
1
70 °C for 2 d to afford 19 as a pale brown solid (28.90 g, 66%). H
Synthesis of Crude BTBP Ligands 24 and 25. General Procedure:
Dicarbohydrazonamide 23 (0.10 g, 0.37 mmol) was suspended in
pyridine (20 mL) and 17 or 22 (0.15 g for 17, 0.16 g for 22,
0.81 mmol, 2.2 equiv.) was added. The suspension was heated un-
der reflux for 3 d. The suspension was allowed to cool to room
temperature, and the insoluble solid was collected by filtration and
washed with pyridine (10 mL). The filtrate was evaporated under
reduced pressure to afford crude 24 or 25 as a yellow semisolid.
Attempted purification by trituration with MeOH and ether,
recrystallization from CH2Cl2/hexane or chromatography on silica
(2.5% MeOH in CH2Cl2) was unsuccessful and pure samples of 24
and 25 could not be obtained.
NMR (400.1 MHz, MeOD): δ = 2.82 (s, 4 H, 3-CH2 and 3Ј-CH2),
1.24 (s, 12 H, 2ϫ2-CH3 and 2ϫ2Ј-CH3) ppm.
Diethyl 3,3Ј-Thiobis(2,2-dimethylpropanoate) (20):[23b,26a,26b,27,38]
Diacid 19 (34.62 g, 147.94 mmol) was dissolved in EtOH (150 mL)
and benzene (100 mL) and concentrated sulfuric acid (5 mL) was
added. The solution was heated under reflux for 24 h. The flask
was allowed to cool to room temperature, and the solution was
diluted with diethyl ether (100 mL). The solution was washed with
water (2ϫ75 mL) and dilute aqueous sodium hydrogen carbonate
solution (2 ϫ 50 mL), dried (MgSO4) and evaporated to yield a
brown liquid (36.85 g), which was purified by vacuum distillation
using a Vigreux column to afford 20 as a colourless liquid (32.33 g,
1
75%). B.p. 108–110 °C at 0.1 Torr. H NMR (400.1 MHz, CDCl3,
6,6Ј-Bis(5,5,9,9-tetramethyl-6,7,8,9-tetrahydro-5H-cyclohepta[e]-
1,2,4-triazin-3-yl)-2,2Ј-bipyridine (24): 1H NMR (400.1 MHz,
CDCl3, Me4Si): δ = 8.96 (dd, J = 7.8 and 0.9 Hz, 2 H, 3-ArH and
3Ј-ArH), 8.56 (dd, J = 7.8 and 0.9 Hz, 2 H, 5-ArH and 5Ј-ArH),
8.05 (t, J = 7.8 Hz, 2 H, 4-ArH and 4Ј-ArH), 1.97–2.02 (m, 4 H,
2ϫ7-CH2), 1.86–1.91 (m, 8 H, 2ϫ6-CH2 and 2ϫ8-CH2), 1.56 (s,
12 H, 4ϫCH3), 1.52 (s, 12 H, 4ϫCH3) ppm.
Me4Si): δ = 4.14 (q, J = 8.0 Hz, 4 H, 2ϫCO2CH2CH3), 2.77 (s, 4
H, 3-CH2 and 3Ј-CH2), 1.26 (t, J = 8.0 Hz, 6 H, 2ϫCO2CH2CH3),
1.23 (s, 12 H, 2ϫ2-CH3 and 2ϫ2Ј-CH3) ppm.
Intramolecular Acyloin Reactions of Diesters 15 and 20. General
Procedure: Dry toluene (300 mL) was placed in an oven-dried flask
and sealed under nitrogen. Freshly cut sodium (10.99 g,
478.12 mmol for 15, 12.82 g, 557.41 mmol for 20, 5 equiv.) was
added, and the flask was heated under reflux until the sodium
melted. Diester 15 or 20 (26.01 g, 95.62 mmol for 15, 32.33 g,
111.48 mmol for 20) was added followed by chlorotrimethylsilane
(60.44 mL, 478.12 mmol for 15, 70.47 mL, 557.41 mmol for 20,
5 equiv.). The mixture was heated under reflux for 24 h. The mix-
ture was allowed to cool to room temperature and filtered through
a sintered disk under nitrogen using a wide Schlenk tube. The solid
residue was washed with toluene (100 mL) and THF (50 mL), and
the filtrate was evaporated under reduced pressure to afford a li-
quid, which was purified by vacuum distillation using a Vigreux
column to afford 16 or 21. The excess sodium was quenched under
nitrogen by washing the solid residue with EtOH (150 mL).
6,6Ј-Bis(5,5,9,9-tetramethyl-5,6,8,9-tetrahydrothiepino[4,5-e]-1,2,4-
triazin-3-yl)-2,2Ј-bipyridine (25): 1H NMR (400.1 MHz, CDCl3,
Me4Si): δ = 8.95 (dd, 2 H, J = 7.8 and 0.8 Hz, 3-ArH and 3Ј-ArH),
8.56 (dd, 2 H, J = 7.8 and 0.8 Hz, 5-ArH and 5Ј-ArH), 8.08 (t, 2 H,
J = 7.8 Hz, 4-ArH and 4Ј-ArH), 2.90 (s, 4 H, 2ϫ6-CH2), 2.89 (s, 4
H, 2ϫ8-CH2), 1.67 (s, 12 H, 4ϫCH3), 1.64 (s, 12 H, 4ϫCH3) ppm.
Synthesis of a PdII Complex of 13: Ligand 13 (0.10 g, 0.154 mmol)
was dissolved in MeOH (20 mL) and Pd(OAc)2 (0.034 g,
0.154 mmol, 1 equiv.) was added. The solution was heated under
reflux for 3 h. The solution was allowed to cool to room tempera-
ture, and a saturated solution of ammonium hexafluorophosphate
in MeOH (10 mL) was added. The solution was evaporated, the
solid was triturated with water (50 mL), filtered, washed with water
(50 mL) and allowed to dry in air to afford the complex as a brown
solid (0.13 g, 81%); m.p. 261–262 °C (dec.). C40H54F12N8P2Pd
(1042.27): calcd. C 46.05, H 5.22, N 10.74, F 21.85, Pd 10.20; found
1,2-Bis(trimethylsilyloxy)-3,3,7,7-tetramethylcyclohept-1-ene
(16):[23] Colourless liquid (12.88 g, 41%). B.p. 72–80 °C at 0.1 Torr.
1H NMR (400.1 MHz, CDCl3, Me4Si): δ = 1.41–1.48 (m, 6 H, 4-
CH2, 5-CH2 and 6-CH2), 0.92 (s, 12 H, 2ϫ3-CH3 and 2ϫ7-CH3),
0.00 (s, 18 H, 2ϫOSi(CH3)3) ppm.
C 45.78, H 4.83, N 10.44, F 21.67, Pd 10.28. IR (Nujol): ν
=
˜
max
2967, 2873, 1611, 1538, 1475, 1459, 1376, 1366, 1264, 1242, 1153,
1118, 1092, 1048, 1025, 935, 896, 835, 827, 627, 556 cm–1. 1H NMR
(400.1 MHz, [D6]acetone): δ = 8.99 (app. s, 2 H, 3-CH and 3Ј-CH),
8.70 (app. s, 2 H, 5-CH and 5Ј-CH), 2.04 (s, 8 H, 4ϫCH2), 1.61 (s,
12 H, 4ϫCH3), 1.56 (s, 30 H, 4ϫCH3, 4-C(CH3)3 and 4Ј-C(CH3)3)
ppm. 13C NMR (100.6 MHz, [D6]acetone): δ = 173.4 (2ϫquat.),
172.7 (2ϫquat.), 167.5 (2ϫquat.), 167.0 (2ϫquat.), 158.0
(2ϫquat.), 152.6 (2ϫquat.), 126.8 (3-CH and 3Ј-CH), 125.2 (5-
CH and 5Ј-CH), 39.6 (2ϫquat.), 38.4 (2ϫquat.), 38.2 (4-C(CH3)3
and 4Ј-C(CH3)3), 33.3 (2ϫCH2), 33.0 (2ϫCH2), 30.3 (4-C(CH3)3
and 4Ј-C(CH3)3), 29.7 (4ϫCH3), 29.2 (4ϫCH3) ppm.
4,5-Bis(trimethylsilyloxy)-3,3,6,6-tetramethyl-2,3,6,7-tetrahydro-
thiepine (21):[23] Colourless liquid (22.12 g, 57%). B.p. 104–108 °C
1
at 0.1 Torr. H NMR (400.1 MHz, CDCl3, Me4Si): δ = 2.44 (br. s,
4 H, 2-CH2 and 7-CH2), 1.07 (s, 12 H, 2ϫ3-CH3 and 2ϫ6-CH3),
0.00 (s, 18 H, 2ϫOSi(CH3)3) ppm.
Synthesis of α-Diketones 17 and 22. General Procedure:[39] The
starting material 16 or 21 (12.88 g, 39.26 mmol for 16, 22.12 g,
63.93 mmol for 21) was dissolved in carbon tetrachloride (130 mL),
and bromine (2.01 mL, 39.26 mmol for 16, 3.27 mL, 63.93 mmol
for 21, 1 equiv.) was added dropwise over 15 min. The solution was
stirred at room temperature for 30 min. The solution was washed
with water (2ϫ50 mL) and saturated aqueous sodium sulfite solu-
tion (50 mL), dried (MgSO4) and evaporated under reduced pres-
sure to yield a liquid, which was purified by vacuum distillation
using a Vigreux column to afford 17 or 22.
Solvent Extraction Experiments: The aqueous solutions were pre-
pared by spiking nitric acid solutions (0.01–4 moldm–3) with stock
solutions of 241Am and 152Eu tracers in nitric acid. The stock solu-
tion of 241Am in 0.5 m HNO3 was prepared by dissolving americ-
ium oxide in 5 m HNO3 and subsequent dilution with water. The
stock solution of 152Eu was prepared by appropriate dilution of
a commercial preparation (REu-2, supplied by Polatom, Poland).
3,3,7,7-Tetramethylcycloheptane-1,2-dione (17):[23–25] Pale brown li-
quid (5.34 g, 74 %). B.p. 158–160 °C at 10–20 Torr. 1H NMR
Eur. J. Org. Chem. 2012, 1509–1519
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1517

F. W. Lewis, L. M. Harwood, et al.
FULL PAPER
Solutions of 12 and 13 (0.0048–0.005 moldm–3) were prepared by
dissolving in the appropriate diluent with or without an additional
phase modifier. Prior to labelling, the aqueous phases were pre-
equilibrated with the neat diluents by shaking them for 4 h at
400 min–1 and volume ratio of 4:1. The organic phases were pre-
equilibrated with the respective nonlabelled aqueous phases by
shaking them for 4 h at 400 min–1 and volume ratio of 1:1. In each
case, 1.2 mL of labelled aqueous phase was prepared from which
200 μL standards were taken (to allow for mass balance calcula-
tions) prior to contacting the aqueous phases with the organic
phases. Each organic phase (1 mL) was shaken separately with each
of the aqueous phases for 6 h at ambient temperature (ca. 25 °C,
nonthermostatted) with a GFL 3005 Orbital Shaker (250 min–1).
After phase separation by centrifugation, two parallel 200 μL ali-
quots of each phase were withdrawn for analysis. The same pro-
cedure was used to investigate the kinetics of 241Am extraction.
Activity measurements of 241Am and 152Eu were performed with a
γ-ray spectrometer EG&G Ortec (USA) with a PGT (USA) HPGe
detector. The γ-lines at 59.5 and 121.8 keV were examined for
241Am and 152Eu, respectively. The errors given in the figures are
1σ and are based on counting statistics only. The approximate solu-
bilities of 12 and 13 were determined by stepwise dissolution of a
known mass of the ligand in the appropriate solvent. The solvent
was then added incrementally in 200 μL aliquots followed by ultra-
sound after each addition until a clear solution was obtained. The
resulting solutions were used in the solvent extraction tests.
Supporting Information (see footnote on the first page of this arti-
cle): NMR stack plots, ESI-MS peaks and species distribution
graphs for lanthanide complexes of 13. Details of stability constant
determination. Tables and graphs of solvent extraction data.
Acknowledgments
We thank the Nuclear Fission Safety Program of the European
Union for support under the ACSEPT (FP7-CP-2007-211 267)
contract. Additional support was provided by the Czech Ministry
of Education, Youth and Sports grant MSM 6840770020. Use of
the Chemical Analysis Facility at the University of Reading is
gratefully acknowledged.
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1
placed in an NMR tube and the H NMR spectrum was recorded.
The appropriate lanthanide salt solution was added to the NMR
tube in 50 μL aliquots (i.e. 0.1 equiv. each time) using a calibrated
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Eur. J. Org. Chem. 2012, 1509–1519

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Received: October 29, 2011
Published Online: January 12, 2012
Eur. J. Org. Chem. 2012, 1509–1519
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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