Palladium-catalyzed cross-coupling of various phosphorus pronucleophiles with chloropyrazines: Synthesis of novel Am(iii)-selective extractants

Article abstract of DOI:10.1039/c2ob25787d

Palladium-catalyzed cross-coupling of (di)chloropyrazines with phosphorus pronucleophiles in the presence of a base gave the phosphorylated pyrazines in 81-95% yields. Based on this methodology a series of appropriately functionalized pyrazines was prepared as potential extractants of trivalent cations from highly acidic nuclear waste. A few hydrophilic derivatives exhibited a very good selectivity for Am³⁺ over Eu³⁺ with separation factors up to 40 at pH 1 at 0.01 mol L^-1 ligand concentration.

Full text of DOI:10.1039/c2ob25787d

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PAPER
Palladium-catalyzed cross-coupling of various phosphorus pronucleophiles
with chloropyrazines: synthesis of novel Am(III)-selective extractants†
Nicolai I. Nikishkin,a Jurriaan Huskens,a Jana Assenmacher,b Andreas Wilden,b Giuseppe Modolob and
Willem Verboom*a
Received 24th April 2012, Accepted 1st June 2012
DOI: 10.1039/c2ob25787d
Palladium-catalyzed cross-coupling of (di)chloropyrazines with phosphorus pronucleophiles in the
presence of a base gave the phosphorylated pyrazines in 81–95% yields. Based on this methodology a
series of appropriately functionalized pyrazines was prepared as potential extractants of trivalent cations
from highly acidic nuclear waste. A few hydrophilic derivatives exhibited a very good selectivity for
Am3+ over Eu3+ with separation factors up to 40 at pH 1 at 0.01 mol L−1 ligand concentration.
reported the Pd(OAc)2/PPh3/dppp-catalyzed reaction of mono-
Introduction
chloropyrazine with alkyl hypophosphites13 and dialkyl phos-
phites.14 Applying a completely different methodology, based on
Owing to its unique electronic and structural properties pyrazine
is of high demand in such areas as construction of multidimen-
sional metal–organic frameworks and supramolecular coordi-
nation complexes,1,2 transition metal catalyzed oxidation,3,4 soft
metal extracting agents, and sensors.5 However, the functionali-
zation of pyrazines still remains a challenging task. Synthetic
strategies leading to substituted pyrazines generally include a
direct metallation followed by a subsequent reaction (quenching)
with an electrophile,6 heteroaromatic nucleophilic substitution,7,8
and different types of transition metal-catalyzed coupling
reactions.
The direct metallation of pyrazines is always complicated by
side reactions such as nucleophilic addition or intermolecular
deprotonation due to the electrophilic nature of this heterocycle.6
The aromatic nucleophilic substitution of halogenated pyrazines
is a rather simple method, but mostly limited to malonate-type
substrates or primary/secondary amines and usually is being
applied for the introduction of alkyl and amino groups,
respectively.7
the thermally induced rearrangement of 2H-azirine-2-phospho-
nates and -phosphine oxides, pyrazine-2,5-diphosphonates and
phosphine oxides were synthesized, respectively.15
Herein we report a simple, general, and versatile method for
the Pd(dppf)Cl2-catalyzed coupling of chlorinated pyrazines
with dialkyl phosphites, secondary phosphines, and secondary
phosphine oxides to give the until now unknown 2,6-disubsti-
tuted pyrazines containing one or two phosphorus substituents.
The lanthanide/actinide extraction properties and the complexa-
tion behavior of selected O,N,O-pyrazine-based ligands will also
be demonstrated.
Results and discussion
Palladium-catalyzed cross-coupling reactions with
chloropyrazines
Palladium-catalyzed P–C cross-coupling of chloropyrazines was
performed by reaction of methyl 6-chloropyrazine-2-carboxylate
(1) with a phosphorus pronucleophile in the presence of a suit-
able base and 1 mol% of Pd(dppf)Cl2 in refluxing acetonitrile
(Scheme 1). Pd(dppf)Cl2 was the catalyst of choice, since it was
previously identified as one of the best second generation cata-
lysts for various carbon–heteroatom couplings that provides high
yields of coupled products in cases where most of the palladium
complexes with other bidentate phosphine ligands were not suc-
cessful.16,17 Also in our case applying other palladium catalysts
like Pd(OAc)2/Buchwald ligand, Pd(PPh3)4, or Pd(dppe)2 did
not give rise to any conversion.
Transition metal-catalyzed couplings are generally used for
carbon–carbon bond formation in pyrazines and include classic
examples like Sonogashira,9 Heck,10 Suzuki,11 and Stille12 reac-
tions. However, only a few examples of carbon–phosphorus
bond formation in pyrazines are known. Montchamp et al.
aLaboratory of Molecular Nanofabrication, MESA+ Institute for
Nanotechnology, University of Twente, P.O. Box 217, 7500 AE
Enschede, The Netherlands. E-mail: w.verboom@utwente.nl
bForschungszentrum Jülich GmbH, Institut für Energie- und
Klimaforschung – Nukleare Entsorgung und Reaktorsicherheit (IEK-6),
52425 Jülich, Germany
†Electronic supplementary information (ESI) available: Copies of the
1H NMR and 13C NMR spectra of the novel compounds. See DOI:
10.1039/c2ob25787d
Reaction of 1 with 1.05 equiv. of diisopropyl phosphite (2) in
the presence of 1.05 equiv. of Huenig base and 1 mol% of Pd-
(dppf)Cl2 for 15 h afforded methyl 6-(diisopropylphosphono)-
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Scheme 1 Palladium-catalyzed coupling reactions on 6-chloropyrazine-2-carboxylate (1).
pyrazine-2-carboxylate (5) in 92% isolated yield. In the 1H
NMR spectra the signals for the pyrazine protons were shifted
from 8.79 and 9.20 ppm in 1 to 9.20 and 9.34 ppm in 5, respect-
ively. The peak at 9.34 ppm for the proton adjacent to the phos-
phonate group was split into a doublet (J = 3.6 Hz) due to
phosphorus–hydrogen coupling. The formation of 5 was also
confirmed by the molecular ion peak in the electrospray mass
spectrum.
Also here the difference in reactivity between diphenylphosphine
(3) and diphenylphosphine oxide (4) is reflected in reaction
times of 3 h and 24 h, respectively. This significant difference in
reaction times can be easily explained considering the lower
acidity of 3 on the one hand and the pyrazine ring deactivation
towards the second oxidative addition (vide infra) to the palla-
dium catalyst by the introduction of an electron-donating diphe-
nylphosphino group on the other hand.
However, under these conditions with diphenylphosphine (3)
and diphenylphosphine oxide (4) no reaction occurred. Appar-
ently, Huenig base is too weak to perform the reaction. In a
study carried out in DMSO the pKa values of diphenylphosphine
(3) and diphenylphosphine oxide (4) were found to be approxi-
mately four and two orders of magnitude larger, respectively,
than that of dialkylphosphites.18 Therefore, using DBU as a
base, reaction of 1 with 3 and 4 afforded methyl 6-(diphenylphos-
phino)- (6) and methyl 6-(diphenylphosphoryl)pyrazine-2-car-
boxylate (7) in 85% and 90% yield, respectively. In the case of
the more acidic diphenylphosphine oxide (4) the reaction was
already completed within 3 h, while starting from diphenylphos-
The 1H NMR spectra of 9, 10, and 11 showed a double reson-
ance for the pyrazine protons at 9.12, 8.24, and 9.39 ppm,
respectively, as a pair of superimposed doublets. The slight
difference in the chemical shifts of the protons is probably due
to a different spatial orientation of the substituents and hindered
rotation of the bulky (i-PrO)2P(O), Ph2P, and Ph2P(O) groups. In
addition to the 1H NMR spectra, all compounds exhibited
characteristic [M + H]+ peaks in their electrospray mass spectra.
With regard to the mechanism of the reaction, we assume that
the reaction follows the established mechanism of the palladium-
catalyzed coupling of aryl halides and phosphorus nucleo-
philes.19 To our knowledge, no detailed mechanistic study of
palladium-catalyzed reactions of phosphorus pronucleophiles
with heteroaryl halides has been reported. However, kinetic and
computational studies on the coupling of aryl halides with
dialkyl phosphites and secondary phosphines have been pub-
lished.20 Kohler et al.21 synthesized stable arylpalladium inter-
mediates containing a dialkylphosphonate fragment. This study
on the ligand influence on the arylpalladium complex stability
revealed that the reductive elimination of the corresponding aryl-
phosphonate happens much faster, almost instantaneously, in the
case of palladium complexes with diphosphine ligands compared
to those with bipyridyls, for example. This indicates that the
reductive elimination is not the rate-limiting step in the catalytic
cycle. At the same time, the presence of an electron-withdrawing
group activates the carbon–chlorine bond towards oxidative
addition of palladium species and accelerates the reaction, as can
be concluded from the difference in reactivities between 3 and 4.
This also explains why our attempts to prepare monosubstituted
pyrazines starting from 2,6-dichloropyrazine (8) were unsuccess-
ful. Even using 1 equiv. of diisopropylphosphite (2) or diphenyl-
phosphine oxide (4) gave rise to a 50 : 50 mixture of 2,6-
disubstituted product and starting material; in the 1H NMR
spectra of the crude reaction mixtures only minute peaks of pos-
sibly monosubstituted product are present.
1
phine (3) the reaction required 20 h. In the H NMR spectra the
characteristic peaks of the pyrazine protons of 1 were shifted
from 8.79 and 9.20 ppm to 8.39 and 9.12 ppm for 6 and to 9.34
and 9.59 ppm (d, J = 3.0 Hz) for 7. All compounds showed
characteristic [M + H]+ peaks in their electrospray mass spectra.
To further explore the scope of the palladium-catalyzed cross-
coupling of phosphorus pronucleophiles with chloropyrazines,
the same series of experiments was performed with 2,6-dichloro-
pyrazine (8) (Scheme 2). Thus reaction of 8 with 2.1 equiv. of
diisopropylphosphite (2) in the presence of 2.1 equiv. of Huenig
base and 1 mol% of Pd(dppf)Cl2 in refluxing acetonitrile for
20 h afforded 2,6-bis(diisopropylphosphono)pyrazine (9) in 90%
yield.
Performing the reaction of 8 under exactly the same conditions
with 2 equiv. of diphenylphosphine (3) and diphenylphosphine
oxide (4) in the presence of 2 equiv. of DBU gave the corres-
ponding 2,6-bis(diphenylphosphino)- (10) and 2,6-bis(diphenyl-
phosphoryl)pyrazines (11) in 81% and 95% yield, respectively.
Synthesis of pyrazine-based lanthanide/actinide ligands
As part of a project aimed at the design and synthesis of novel
extracting agents for actinide/lanthanide separation with
improved selectivity for nuclear waste treatment,22–24 we have
Scheme 2 Palladium-catalyzed coupling reactions on 2,6-dichloropyr-
azine (8).
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developed a series of pyrazine-based lipophilic and water-
soluble ligands 12, 13, 15, 20, and 21, containing amide, phos-
phinoxide, phosphonate and in one case phosphine sulfide moi-
eties. The lipophilic ligands are typically used to extract f-block
elements from highly acidic radioactive waste solutions, while
the water-soluble complexants are applied to strip metal ions
back.25 Pyridine-based ligands, picolinamides for instance, are
known to lose their extraction ability significantly at a pH < 3,
due to protonation of the pyridine nitrogen.25 Pyrazine will be
with trimethylbromosilane in acetonitrile and subsequent
hydrolysis with NaOH in methanol.
The H NMR spectrum of 12 shows a triplet (J = 1.8 Hz) for
the pyrazine protons at 8.91 ppm, and complete disappearance of
the characteristic phosphonate isopropyl group signals. The elec-
trospray mass spectrum of 12 gave the correct [M + H]+,
2[M + H]+, and 3[M + H]+ peaks.
1
Simple oxidation of diphosphine 10 with 2 equiv. of elemen-
tary sulphur in refluxing toluene gave pyrazine-2,6-diylbis-
(diphenylphosphine sulfide) (13) in quantitative yield
(Scheme 3). In addition to the correct peak of the molecular ion
less acid sensitive, since the pyrazine nitrogen (pKb,pyrazine
13.8) is much less basic than that of pyridine (pKb,pyridine
=
=
8.8).26 It was anticipated that the introduction of phosphinoxides
or phosphonates will further decrease the basicity of the pyrazine
nitrogens, hence increasing the affinity towards actinides over
lanthanides, the first ones being slightly softer cations than the
lanthanides. In general, picolinamides show a reasonable extrac-
tion selectivity of Am(III) over lanthanides, although the amide
substituents and the diluent play an important role.27 The well
known carbamoylphosphinoxides are highly efficient extractants
among the bidentate organophosphorus compounds for the
recovery of trivalent actinides and lanthanides from highly acidic
nuclear waste solutions.22,23
in the electrospray mass spectrum, the H NMR spectrum of 13
1
reveals two overlapped doublets for the pyrazine protons at
9.79 ppm, which is 0.40 ppm higher, than in the case of diphos-
phorylpyrazine 11, with a negative spin-coupling constant (J =
−4.2 Hz), as can be concluded from the decreased intensity of
the inner lines of the multiplet.28
Initially, sodium hydrogen(6-(morpholine-4-carbonyl)pyrazin-
2-yl)phosphonate (15) was prepared in 59% yield in two steps
starting with amidation of ester 5 with morpholine in the pres-
ence of MgCl2 29 in methanol and followed by phosphonate clea-
vage of the resulting product 14 with trimethylbromosilane
(Scheme 4). However, due to the modest reactivity of ester 5,
amidation of it required a 3-fold excess of the amine, which in
turn promoted morpholine alkylation by diisopropyl phospho-
nate, complicating the purification and significantly decreasing
the yield of 14. Therefore, the synthetic sequence was altered.
Starting from 6-chloropyrazine-2-carbonyl chloride (16), the cor-
responding amide 17 was obtained in quantitative yield upon
reaction with morpholine. Performing P–C coupling of 17 with
2, following the established procedure, afforded 14 in 90% yield.
The 1H NMR spectrum reveals two singlets for the pyrazine
protons at 8.66 and 8.88 ppm, also displaying characteristic
signals for the diisopropylphosphonate group at 4.67–4.80 and
1.36 ppm (d). Treatment of 14 with trimethylbromosilane in
acetonitrile and subsequent hydrolysis with NaOH in methanol
The synthesis of the pyrazine-based ligands 12, 13, 15, 20,
and 21 is mainly based on the above described methodology.
Pyrazine-2,6-diyldiphosphonic acid (12) was synthesized in 98%
yield (Scheme 3) by performing phosphonate ester cleavage of 9
1
gave amidophosphonate 15 in 96% yield. In its H NMR spec-
trum, the characteristic peaks of the pyrazine protons did not
Scheme 3 Synthesis of ligands 12 and 13.
undergo a significant shift compared to 14, however, the
Scheme 4 Synthesis of amidophosphonate 15.
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Scheme 5 Synthesis of ligand 20.
Fig. 1 D ratios of 241Am(III) and 152Eu(III) and SF values as a function
of the initial HNO3 concentration by ligand 11. Organic phase:
0.05 mol L−1 11 in TPH. Aqueous phase: variable concentrations of
HNO3, tracers: 241Am, 152Eu, mixing time: 60 min, T = 22 °C 1 °C.
Scheme 6 Synthesis of ligand 21.
of the ligands were contacted with nitric acid solutions
(0.01 mol L−1–4 mol L−1) containing 241Am and 152Eu radio-
tracers. These conditions are commonly used for testing the
extraction properties of extractants relevant for nuclear waste
treatment.
The metal distribution ratio DM was calculated according to
eqn (1) and the percentage of metal ions retained in the water
phase after extraction using eqn (2).
successful cleavage of the phosphonate ester group was proven
by the complete absence of the isopropyl signals as present in
14. The electrospray mass spectrum of 15 demonstrated the
molecular ion peak.
Surprisingly, pyrazine ester 7 proved to be completely unreac-
tive towards dioctylamine, hence it was decided to apply the
same approach, as described for 15, and to perform amidation
prior to P–C coupling. Treatment of pyrazine acid chloride 16
with dioctylamine gave pyrazine dioctylamide 18 in quantitative
yield. Reaction of 18 with 1 equiv. of diphenylphosphine (3) in
the presence of 1 equiv. of DBU and 1 mol% of Pd(dppf)Cl2 in
refluxing acetonitrile overnight, followed by oxidation of the
diphenylphosphino group with hydrogen peroxide in acetone,
afforded 6-(diphenylphosphoryl)-N,N-dioctylpyrazine-2-carbox-
½Mꢀorg
½Mꢀaq
DM
¼
ð1Þ
1
%Meq;aq
¼
ꢁ 100%
ð2Þ
1 þ DM
The separation factor (SF) between Am(III) and Eu(III) was cal-
culated using eqn (3).
1
amide (20) in 75% yield (Scheme 5). In the H NMR spectrum
the signals for the pyrazine protons of 18 at 8.62 and 8.80 ppm
were shifted to 8.24 and 8.72 ppm, respectively, for 19 and to
8.99 (d, J = 3.3 Hz) and 9.41 ppm, after oxidation of the phos-
phine, for 20. The electrospray mass spectrum confirmed the for-
mation of 20, exhibiting the molecular ion peak.
Eu
DEu
SF
¼
ð3Þ
Am DAm
The extraction results of ligand 11 are presented in Fig. 1. It
shows that ligand 11 is a poor extractant under the tested con-
ditions. The distribution ratios for Am(III) and Eu(III) are below 1
in the region between 0.01 and 4 mol L−1 nitric acid. Since the
D-values decrease with increasing acidity, it is assumed that 11
is protonated at the central N atom, and the poor extraction of
Am(III) (DAm = 0.5 at 0.01 mol L−1 HNO3) may be explained by
ion-pair extraction. However, this is only a hypothesis and needs
to be studied by additional extraction studies e.g. testing syner-
gistic mixtures with lipophilic anions.
The solubility of 11 in the hydrocarbon diluent TPH (Total
Petroleum Hydrocarbon/hydrogenated tetrapropene) was moder-
ate. Solubility problems were also encountered with ligand 13,
in which the two phosphoryl oxygens were replaced by sulphur-
donor atoms. Ligand 13 shows no extraction efficiency for both
Am(III) and Eu(III); distribution ratios were below 0.01 in the
entire HNO3 region tested.
Diisopropyl (6-(dioctylcarbamoyl)pyrazin-2-yl)phosphonate
(21) was obtained by reaction of 18 with 1.05 equiv. of diisopro-
pyl phosphite (2) in the presence of 1.05 equiv. of Huenig base
and 1 mol% of Pd(dppf)Cl2 in refluxing acetonitrile overnight in
1
87% yield (Scheme 6). In the H NMR spectrum the signals for
the pyrazine protons of 18 at 8.62 and 8.80 ppm were shifted to
8.98 ppm (d, J = 3.6 Hz) and 9.08 ppm, respectively, for 21.
The formation of 21 was also confirmed by the molecular ion
peak in the electrospray mass spectrum.
Extraction results
Lipophilic ligands
Preliminary solvent extraction experiments were carried out to
determine the ability of the new lipophilic ligands 11, 13, 20,
and 21 to extract f-block elements from highly acidic radioactive
solutions into an organic phase. Therefore, organic solutions
To increase the solubility and possibly the affinity for trivalent
actinides with the new pyrazine-based ligands, two modifications
were realized: (a) one phosphoryl group was replaced by an
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amide moiety containing two lipophilic n-octyl groups (ligand
20) and (b) the residual phosphoryl was replaced by a phospho-
nate group bearing isopropoxy moieties (ligand 21). The extrac-
tion results showed, however, that the ligands 20 and 21 are not
able to extract f-block elements like Am(III) and Eu(III) from
highly acidic radioactive waste solutions; 95% up to 100% of the
radionuclides Am and Eu were still remaining in the aqueous
phase.
Water-soluble ligands
Fig. 2 D ratios of 241Am(III) and 152Eu(III) as a function of the initial
pH and the influence of the concentration of ligand 12. Organic phase:
0.2 mol L−1 TODGA + 5 vol% 1-octanol in TPH. Aqueous phase:
0.5 mol L−1 NH4NO3, variable pHini, variable concentrations of ligand
12, tracers: 241Am, 152Eu, mixing time: 60 min, T = 22 °C 1 °C.
Actinide separation processes developed over the last 20 years
are predominantly based on multi-cycle processes, i.e. the com-
bined extraction of actinides (An(III)) and lanthanides (Ln(III))
from the PUREX raffinate (Plutonium Uranium Recovery by
Extraction) followed by their subsequent group separation. In
single-cycle processes, on the other hand, An(III) + Ln(III) are
also simultaneously separated. Following an An(III)/Ln(III) co-
extraction step, the trivalent actinides are selectively back-
extracted (stripped) from the loaded organic phase, e.g. using a
hydrophilic polyaminocarboxylic acid such as diethylenetriami-
nepentaacetic acid (DTPA). However, they have a limited solubi-
lity, which also greatly depends on the pH of the aqueous
solution. Among the most important developments of this
process, in Europe the so-called “innovative SANEX” (Selective
ActiNide EXtraction) concept is being studied.30,31 It is basically
a DIAMEX (DIAMide EXtraction) process (An(III) and Ln(III)
co-extraction) with selective back extraction of An(III) from the
loaded organic phase. Instead of a water-soluble complexing
agent such as DTPA, which requires in most cases buffering
agents to adjust the pH, the search is for stronger acid resistant
water-soluble ligands.
Table 1 Percentages of retained ions in the aqueous phase and Eu/Am
separation factors using ligands 12 and 15
Ligand
conc.
[mol
Ligand 12
Ligand 15
Initial
pH
%
%
%
%
L−1
]
Amaq,eq Euaq,eq SFEu/Am Amaq,eq Euaq,eq SFEu/Am
0
1
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
2.8
2.4
1.6
0.4
0.4
0.4
0.3
2.0
11.8
26.4
30.3
62.0
94.1
96.9
98.5
99.8
99.9 ∼1
99.9 ∼1
99.9 ∼1
7.2
6.3
4.5
4.3
2.8
2.4
1.6
1.3
2.3
3.4
5.7
5.3
2.1
10.3
22.9
24.9
8.5
61.4
87.0
84.2
0.4
0.4
0.4
0.3
0.3
0.5
1.1
1.3
0.3
1.0 11
3.2
4.5
0.9 11
10.3 14
35.2 12
30.5 12
7.2
6.3
4.5
4.3
7.4
7.2
5.6
4.3
6.7
1.3
0.001
0.01
0.1
29.3
75.8
84.7
86.3
98.5
99.8
99.9
99.9
99.9
99.9
99.9
99.9
20
23
15
15
40
26
21
18
9.0
7.1
In the present study the new hydrophilic ligands 12 and 15
were tested for selective stripping of Am(III) from loaded organic
solutions into an aqueous phase. An organic solution containing
4.6
TODGA (N,N,N′,N′-tetra-n-octyl diglycolamide) (0.2 mol L−1
)
and 5 vol% 1–octanol in TPH was used as a solvent.32 The
TODGA molecule is known to efficiently extract trivalent lantha-
nides and actinides from moderate to high nitric acid concen-
trations.33,34 A weighted amount of the hydrophilic ligand was
dissolved in an aqueous NH4NO3 (0.5 mol L−1) solution fol-
lowed by pH adjustment (HNO3 or NaOH) and addition of
traces of 241Am(III) and 152Eu(III). The nitrate ion was used as a
salting-out agent to compensate the metal charge, since TODGA
extracts metals only as neutral species (solvating extraction
mechanism).35
Calculated using eqn (2) and (3) using the distribution ratios from Fig. 2
and 3, respectively.
Ligand 12 exhibits a very strong extractability for 241Am and
152Eu. At a ligand concentration of 0.1 mol L−1 nearly 100% of
Am(III) and Eu(III) are complexed in the aqueous phase
(Table 1). As expected, the distribution ratios increase with
decreasing ligand concentration. However, the one of 152Eu
increases at a much higher rate than that of 241Am. Therefore, it
becomes possible to separate Am over Eu at lower ligand con-
centrations. The separation factor SFEu/Am of Eu over Am at an
initial pH of 1 increases from 4.6 to 40, upon decreasing the
ligand concentration from 0.1 mol L−1 to 0.01 mol L−1
(Table 1). While decreasing the ligand concentration to
0.001 mol L−1 the distribution ratios increase further.
The higher the SFEu/Am is, the better the selectivity of the
water-soluble ligand for Am(III) versus Eu(III) is.
Fig. 2 displays the distribution ratios as a function of the
initial pH of different concentrations of ligand 12. For compari-
son, the results of the reference system (TODGA) are expressed
by the dotted lines in Fig. 2. TODGA shows a slightly higher
affinity for Eu(III) over Am(III). High distribution ratios for Am
(III) and Eu(III) were obtained and they were not affected by the
initial pH of the aqueous phase due to the salting-out effect of
NO3−. The D values for Am are between 34 and 76, whereas
higher D values (250–323) were obtained for Eu, resulting in
SFEu/Am values between 4.5 and 7.2.
It is possible to adjust conditions, which are of great interest
for the innovative-SANEX concept.29 At a ligand concentration
of 0.001 mol L−1 and an initial pH between 2 and 4, Eu(III) is
held back preferentially in the organic phase, whereas Am(III) is
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containing ligands make them very suitable candidates to be
applied in the innovative SANEX process.
Experimental
General
The solvents, catalyst, and all reagents were obtained from com-
1
mercial sources and used without further purification. H NMR
and 13C NMR spectra were recorded on a Varian Unity INOVA
(300 MHz) spectrometer. 1H NMR chemical shift values
(300 MHz) are reported as δ using the residual solvent signal as
an internal standard (CDCl3, δ = 7.257). 13C NMR chemical
shift values (75 MHz) are reported as δ using the residual
solvent signal as an internal standard (CDCl3, δ = 77.0 ppm).
Electrospray ionization (positive mode) mass spectra were
recorded on a WATERS LCT (Micromass KC-340) mass spec-
trometer. Infrared spectra were taken on a Thermo Scientific
spectrometer. All reactions were performed under a nitrogen
atmosphere.
Fig. 3 D ratios of 241Am(III) and 152Eu(III) as a function of pHini and
the influence of the concentration of ligand 15. Organic phase:
0.2 mol L−1 TODGA + 5 vol% 1-octanol in TPH. Aqueous phase:
0.5 mol L−1 NH4NO3, variable pHini, variable concentrations of ligand
15, tracers: 241Am, 152Eu, mixing time: 60 min, T = 22 °C 1 °C.
complexed selectively in the aqueous phase. The DAm values are
between 0.3 and 0.2 (Fig. 2), which expresses that 76% to 86%
of the metal is retained in the aqueous phase. However, the DEu
values are between 2 and 7, which means that >70% of the metal
is kept in the organic phase. In a multi-step counter-current
extraction process these conditions can be used for a complete
group separation. As the ligand concentration is very low, the
system may be very sensitive to loading effects.
General procedure for the palladium-catalyzed P–C coupling of
monochloropyrazines 1, 17 and 18 with diisopropyl phosphite.
Formation of 5, 14, and 21
To a solution of chloropyrazines 1, 17, 18 (10 mmol) and Pd
(dppf)Cl2 (0.073 g, 1 mol%) in CH3CN (50 mL) were sub-
sequently added HPO(O-i-Pr)2 (1.7 mL, 10.5 mmol) and
i-Pr2NEt (1.8 mL, 10.5 mmol). The resulting mixture was
refluxed for 3 h and then all the volatiles were removed in vacuo.
The residue was partitioned between H2O (50 mL) and EtOAc
(50 mL). The organic phase was dried over Na2SO4 and the sol-
ution was passed through a short plug of silica. The resulting
solution was dried in vacuo yielding the coupled products as
oils.
The back extraction results with ligand 15 are depicted in
Fig. 3 and also summarized in Table 1. At a low ligand concen-
tration of 0.01 mol L−1 or 0.001 mol L−1, the extraction of Am
and Eu is less pronounced, compared to ligand 12; only a moder-
ate amount (<50%) of the radionuclides is extracted into the
aqueous phase (Table 1). However, at a ligand concentration of
0.1 mol L−1, the conditions are again interesting for the innova-
tive-SANEX concept. The DAm values are <1 in the initial pH-
range between 2 and 4, but those of Eu are >1, which makes a
selective separation of both radionuclides possible. Although the
observed separation factors are lower than those of ligand 12
(SFEu/Am ∼ 10–14), due to the higher ligand concentrations, the
process will be less sensitive to metal loading effects. This
makes this ligand a good candidate for the innovative SANEX
process.36
Diisopropyl (6-(methoxycarbonyl)pyrazin-2-yl)phosphonate
1
(5). Yield 2.78 g, 92%. H NMR (CDCl3): δ = 9.34 (d, 1 H,
3JHP = 3.6 Hz, PyzH), 9.20 (s, 1 H, PyzH), 4.92–4.82 (m, 2 H,
CH(CH3)2), 4.02 (s, 3 H, CH3OC(O)), 1.42 and 1.36 (d, 6 H, J
= 6.0 Hz, CH(CH3)2). 13C NMR: δ = 164.2, 150.3 (d, JCP
=
4.2 Hz), 149.9 (d, JCP = 4.2 Hz), 147.6 (m), 147.5 (m), 73.3
2
(t, JCP = 6.8 Hz), 53.4, 24.2–24.8 (set of doublets). IR
Conclusions
(νmax/cm−1): 2981, 1728, 1441, 1387, 1377, 1311, 1251, 1125,
1102, 985, 894, 780. MS (ES+) (m/z): 303.0 [M + H]+.
HRMS-TOF (m/z): [M + H]+ calcd 303.1110, found 303.1108.
A simple method has been developed for the preparation of a
novel class of compounds, viz. 2,6-disubstituted pyrazines
bearing one or two phosphorus substituents, comprising the Pd
(dpppf)Cl2-catalyzed coupling of (di)chloropyrazines with phos-
phorus-containing pronucleophiles. The introduction of an elec-
tron-withdrawing group enhances the rate of the second coupling
step in the case of dichloropyrazines. From a series of pyrazine-
based lipophilic and water-soluble ligands, prepared according to
this methodology, the latter ones exhibit a very good selectivity
for Am3+, used as a typical representative of the minor actinides,
over lanthanides. This underlines the importance of further
development of pyrazine-based ligands. On the other hand, its
relatively simple synthesis, the extraction behavior and the
reduced sensitivity towards acid compared to pyridine-
Diisopropyl (6-(morpholino-4-carbonyl)pyrazin-2-yl)phospho-
1
nate (14). Yield 3.22 g, 90%. H NMR (CDCl3): δ = 8.88 (s, 1
H, PyzH), 8.66 (s, 1 H, PyzH), 4.80–4.67 (m, 2 H, CH(CH3)2),
3.84–3.79 (m,
4 H, OCH2CH2N), 3.75–3.64 (m, 4 H,
OCH2CH2N), 1.36 (d, 12 H, J = 6.0 Hz, CH(CH3)2). 13C NMR:
1
δ = 165.8, 149.2, 148.5, 147.8 (d, JCP = 16.2 Hz), 147.1 (d,
2JCP = 4.3 Hz), 73.3 (d, JCP = 3.0 Hz), 73.2 (d, JCP = 3.0 Hz),
2
2
3
67.9, 67.0, 48.1, 43.5, 25.6–25.0 (set of doublets, JCP = 1.5
Hz). IR (νmax/cm−1): 2925, 2855, 1636, 1466, 1376, 1253, 1168,
1009, 887, 768. HRMS-TOF (m/z): [M + H]+ calcd 358.1532,
found 358.1536.
5448 | Org. Biomol. Chem., 2012, 10, 5443–5451
This journal is © The Royal Society of Chemistry 2012

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1
(d, 12 H, J = 6.0 Hz, CH(CH3)2). 13C NMR: δ = 151.1 (d, JCP
Diisopropyl (6-(dioctylcarbamoyl)pyrazin-2-yl)phosphonate
1
2
2
(21). Yield 4.45 g, 87%. H NMR (CDCl3): δ = 9.08 (s, 1 H,
= 17.3 Hz), 149.3 (t, JCP = 4.1 Hz), 148.9 (t, JCP = 4.1 Hz),
3
1
2
2
PyzH), 8.98 (d, 1 H, JHP = 3.6 Hz, PyzH), 4.86–4.76 (m, 2 H,
148.1 (d, JCP = 17.3 Hz), 73.2 (d, JCP = 3.0 Hz), 73.1 (d, JCP
2
2
CH(CH3)2), 3.50 and 3.40 (t, 2 H, J = 7.5 Hz, CH2N),
1.15–1.75 (m, 36 H, AlkH), 0.86 (t, 6 H, J = 7.6 Hz, CH3). 13C
NMR: δ = 163.2, 149.0, 148.6, 147.7 (d, 1JCP = 16.5 Hz), 147.2
= 3.0 Hz), 73.0 (d, JCP = 3.0 Hz), 72.9 (d, JCP = 3.0 Hz),
24.0–24.5 (set of doublets, JCP = 1.5 Hz). IR (νmax/cm−1):
3
2982, 1377, 1238, 1179, 1143, 1105, 964. MS (ES+) (m/z):
409.2 [M − H]+. HRMS-TOF (m/z): [M + H]+ calcd 409.1657,
found 409.1654.
2
2
2
(d, JCP = 4.5 Hz), 73.2 (d, JCP = 3.0 Hz), 73.1 (d, JCP = 3.0
Hz), 32.1, 31.8, 29.8, 29.6, 29.5, 28.4, 28.0, 27.3, 26.5, 22.8,
21.9, 20.8, 14.3. IR (νmax/cm−1): 2979, 1638, 1519, 1386, 1255,
1143, 995, 883, 766. HRMS-TOF (m/z): [M + H]+ calcd
512.3617, found 512.3621.
2,6-Bis(diphenylphosphino)pyrazine (10). To a solution of 8
(1.49 g, 10 mmol) and Pd(dppf)Cl2 (0.146 g, 2 mol%) in
CH3CN (50 mL) were subsequently added HPPh2 (3.4 mL,
20 mmol) and DBU (3.0 mL, 20 mmol). The resulting mixture
was refluxed for 24 h and then all the volatiles were removed in
vacuo. The residue was partitioned between H2O (50 mL) and
EtOAc (50 mL). The organic phase was dried over Na2SO4 and
the solution was passed through a short plug of silica. The result-
ing solution was dried in vacuo. The crude product was crystal-
lized from toluene–hexane affording pure 10 (3.63 g, 81%). Mp
116–118 °C. 1H NMR (CDCl3): δ = 8.24 (d, 2 H, 3JHP = 3.0 Hz,
PyzH), 7.28–7.24 (m, 20 H, ArH). 13C NMR: δ = 153.4 (d, 1JCP
Methyl 6-(diphenylphosphoryl)pyrazine-2-carboxylate (7). To
a solution of 1 (1.74 g, 10 mmol), Pd(dppf)Cl2 (0.073 g,
1 mol%) and HP(O)Ph2 (2.02 g, 10 mmol) in CH3CN (50 mL)
was added DBU (1.5 mL, 10 mmol). The resulting mixture was
refluxed for 3 h and then all the volatiles were removed in vacuo.
The residue was partitioned between H2O (50 mL) and EtOAc
(50 mL). The organic phase was dried over Na2SO4 and the sol-
ution was passed through a short plug of silica. The resulting
solution was dried in vacuo yielding 7 as an amber oil (3.04 g,
1
2
1
= 13.5 Hz), 151.8 (d, JCP = 13.5 Hz), 149.5 (d, JCP = 1.3 Hz),
90%). H NMR (CDCl3): δ = 9.59 (s, 1 H, PyzH), 9.34 (d, 1 H,
2
3JHP = 3.0 Hz, PyzH), 7.97–7.90 (m, 4 H, ArH), 7.53–7.40 (m,
6 H, ArH), 4.02 (s, 3 H, CH3OC(O)). 13C NMR: δ = 166.8,
149.2 (d, JCP = 1.3 Hz), 132.9, 132.8, 132.6, 132.3, 132.1,
131.5, 130.1, 129.1, 129.0, 128.9, 128.7, 128.5. MS (ES+) (m/z):
448.9 [M + H]+. HRMS-TOF (m/z): [M + H]+ calcd 449.1336,
found 449.1335.
1
151.2 (d, JCP = 17.3 Hz), 148.6, 148.3, 146.9, 133.1, 132.5,
132.4, 131.3, 131.0, 129.6, 129.0, 128.8, 128.7, 128.6, 128.5,
128.3, 56.5. IR (νmax/cm−1): 2954, 1750, 1522, 1439, 1399,
1306, 1198, 1167, 1152, 1121, 972, 861, 725. MS (ES+) (m/z):
362.2 [M + Na]+. HRMS-TOF (m/z): [M + H]+ calcd 339.0899,
found 339.0898.
2,6-Bis(diphenylphosphoryl)pyrazine (11). To a solution of 8
(1.49 g, 10 mmol) and Pd(dppf)Cl2 (0.146 g, 2 mol%) and HP
(O)Ph2 (4.04 g, 20 mmol) in CH3CN (50 mL) was added DBU
(3.0 mL, 20 mmol). The resulting mixture was refluxed for 3 h
and then all the volatiles were removed in vacuo. The residue
was partitioned between H2O (50 mL) and EtOAc (50 mL). The
organic phase was dried over Na2SO4 and the solution was
passed through a short plug of silica. The resulting solution was
dried in vacuo. The crude product was crystallized from toluene–
hexane to give 11 (4.56 g, 95%). Mp 206–208 °C. 1H NMR
General procedure for the palladium-catalyzed P–C coupling of
monochloropyrazines 1 and 18 with diphenylphosphine.
Formation of 6 and 19
To a solution of monochloropyrazines 1 and 18 (10 mmol) and
Pd(dppf)Cl2 (0.073 g, 1 mol%) in CH3CN (50 mL) were sub-
sequently added HPPh2 (1.7 mL, 10 mmol) and DBU (1.5 mL,
10 mmol). The resulting mixture was refluxed for 20 h and then
the solvent was removed in vacuo. The residue was partitioned
between H2O (50 mL) and EtOAc (50 mL). The organic phase
was dried over Na2SO4 and all the volatiles were removed
in vacuo. The resulting crude phosphines 6 and 19 were charac-
terized as their phosphine oxides.
3
5
(CDCl3): δ = 9.39 (dd, 2 H, JHP = 3.6 Hz, JHP = −3.3 Hz,
PyzH), 7.57–7.50 (m, 12 H, ArH), 7.29–7.25 (m, 8 H, ArH).
13C NMR: δ = 149.3 (d, JCP = 22.5 Hz), 148.6, 132.8–132.0
1
(m), 131.5, 130.1, 129.1–128.2 (m), 123.0. MS (ES+) (m/z):
480.8 [M + H]+. HRMS-TOF (m/z): [M + H]+ calcd 481.1235,
found 481.1231.
General procedure for phosphonate 9 and 14 deprotection.
Formation of 12 and 15
1
6: yield 85%, H NMR (CDCl3): δ = 9.12 (s, 1 H, PyzH),
3
8.39 (d, 1 H, JHP = 1.5 Hz, PyzH), 7.41–7.35 (m, 10 H, ArH),
3.99 (s, 3 H, CH3OC(O)). MS (ES+) (m/z): 323.1 [M + H]+.
To a solution of dialkylphosphonates 9 and 14 (5 mmol) in
CH3CN (50 mL) was added Me3SiBr (3 equiv. per phosphonate
group). The resulting mixture was refluxed for 18 h and all the
volatiles were removed in vacuo. The residue was dissolved in
CH3OH (50 mL), whereupon NaOH (0.2 g, 5 mmol) was added.
The resulting solution was stirred for 1 h and then acidified with
1 M HCl and dried in vacuo affording the corresponding amido-
phosphonic acids 12 and 15.
2,6-Bis(diisopropylphosphono)pyrazine (9). To a solution of 8
(1.49 g, 10 mmol) and Pd(dppf)Cl2 (0.146 g, 2 mol%) in
CH3CN (50 mL) were subsequently added HPO(O-i-Pr)2
(3.5 mL, 21.0 mmol) and i-Pr2NEt (3.7 mL, 21.0 mmol). The
resulting mixture was refluxed for 3 h and then all the volatiles
were removed in vacuo. The residue was partitioned between
H2O (50 mL) and EtOAc (50 mL). The organic phase was dried
over Na2SO4 and the solution was passed through a short plug
Pyrazine-2,6-diyldiphosphonic acid (12). Yield 2.35 g, 98%.
1
3
of silica. The resulting solution was dried in vacuo to give 9
Mp 205–206 °C. H NMR ((CD3)2SO): δ = 8.91 (t, 2 H, JHP =
(3.67 g, 90%). 1H NMR (CDCl3): δ = 9.12 (d, 2 H, JHP
=
1.8 Hz, PyzH). 13C NMR: δ = 154.3 (d, JCP = 15.8 Hz), 151.4
3
1
1
2
2
4.5 Hz, PyzH), 4.86–4.76 (m, 4 H, CH(CH3)2), 1.37 and 1.31
(d, JCP = 15.8 Hz), 147.6 (t, JCP = 4.5 Hz), 147.3 (t, JCP
=
This journal is © The Royal Society of Chemistry 2012
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4.5 Hz). MS (ES+) (m/z): 241.0 [M + H]+. HRMS-TOF (m/z):
stirring the reaction mixture for 30 min all the volatiles were
removed in vacuo and the residue was partitioned between H2O
(30 mL) and CHCl3 (30 mL). The organic phase was dried over
Na2SO4 and passed through a short plug of silica, giving 20
after evaporation of the solvent as a yellow oil (2.05 g, 75%). 1H
[M + H]+ calcd 240.9779, found 240.9772.
(6-(Morpholino-4-carbonyl)pyrazin-2-yl)phosphonic acid (15).
1
Yield 2.63 g, 96%. H NMR ((CD3)2SO): δ = 8.95 and 8.85 (s,
1 H, PyzH), 3.65 (bs, 4 H, OCH2CH2N), 3.55 and 3.44 (t, 2 H,
3
NMR: δ = 9.41 (s, 1 H, PyzH), 8.99 (d, 1 H, JHP = 3.3 Hz,
J = 3.0 Hz, OCH2CH2N). 13C NMR: δ = 163.7, 148.1, 147.4,
PyzH), 7.85–7.75 (m, 8 H, ArH), 7.60–7.35 (m, 12 H, ArH),
3.46 and 3.11 (t, 2 H, J = 7.5 Hz, CH2N), 1.70–0.70 (m, 30 H,
1
1
145.7 (d, JCP = 3.8 Hz), 143.6 (d, JCP = 5.3 Hz), 67.0, 66.9,
47.9, 43.1. IR (νmax/cm−1): 2971, 1632, 1362, 1442, 1268,
1068, 1025, 1008, 803, 767. HRMS-TOF (m/z): [M + H]+ calcd
274.0593, found 274.0585.
1
AlkH). 13C NMR: δ = 165.8, 150.1 (d, JCP = 17.3 Hz), 148.3,
147.3, 145.8, 133.0, 132.4, 132.2, 131.3, 130.9, 129.5, 129.0,
128.9, 128.7, 128.6, 128.5, 128.4, 32.0, 31.9, 29.6, 29.5, 29.4,
29.3, 29.0, 27.2, 26.6, 22.9, 22.8, 20.8, 14.3. IR (νmax/cm−1):
2922, 2852, 1631, 1436, 1209, 1114, 1013, 723, 694.
HRMS-TOF (m/z): [M + H]+ calcd 548.3406, found 548.3405.
2,6-Bis(diphenylthiophosphoryl)pyrazine (13). A suspension
of 10 (4.48 g, 10 mmol) and elementary sulfur (0.64 g,
20 mmol) in toluene (100 mL) was refluxed overnight forming a
brown solution. Then all the volatiles were removed in vacuo.
The residue was recrystallized from hot EtOH giving 13 as
Solvent extraction studies
1
orange crystals (4.51 g, 88%). Mp 154–157 °C. H NMR: δ =
9.79 (dd, 2 H, 3JHP = 3.6 Hz, 5JHP = −4.2 Hz, PyzH), 7.56–7.45
(m, 12 H, ArH), 7.33–7.26 (m, 8 H, ArH). 13C NMR: δ = 151.9
The batch experiments were performed in 2 mL glass vials.
Organic and aqueous phases (500 μL) were prepared as
described below, spiked with 10 μL of radiotracer (241Am,
152Eu, approx. 25 kBq mL−1) and shaken by a vortex mixer for
60 min. The radiotracers were supplied by Isotopendienst
M. Blaseg GmbH, Waldburg (Germany). Separation of the
phases by centrifugation was followed by sampling 200 μL of
each phase for analysis using a high-purity germanium spec-
trometer system obtained from EG&G Ortec, München,
Germany, and equipped with the gamma vision software. The
γ-lines at 59.5 and 121.8 keV were examined for 241Am and
152Eu, respectively. The distribution ratio DM was measured as
the ratio between the radioactivity of an isotope in the organic
and the aqueous phases. Distribution ratios between 0.01 and
100 exhibit a maximum error of 5%. The error may be up to
20% for smaller and larger values.
1
1
2
(d, JCP = 11.3 Hz), 150.5 (d, JCP = 11.3 Hz), 149.5 (d, JCP
=
2
3.8 Hz), 149.2 (d, JCP = 3.8 Hz), 132.5, 132.4, 132.2, 131.6,
130.4, 128.8, 128.7, 128.6. MS (ES+) (m/z): 512.9 [M + H]+.
HRMS-TOF (m/z): [M + H]+ calcd 513.0778, found 513.0775.
(6-Chloropyrazin-2-yl)(morpholino)methanone (17). To a sol-
ution of acid chloride 16 (5.3 mmol) in dry CH2Cl2 (25 mL)
was added dropwise a solution of morpholine (0.48 mL,
5.5 mmol) and Et3N (1.5 mL, 10 mmol) in dry CH2Cl2 (25 mL).
The resulting mixture was stirred for 2 h and then all the volatiles
were removed in vacuo. The residue was partitioned between
H2O (30 mL) and EtOAc (70 mL). The organic phase was dried
over Na2SO4 and the solvent was removed in vacuo, giving 17
1
in quantitative yield as a pale yellow oil. H NMR: δ = 8.88 and
8.66 (s, 1 H, PyzH), 3.83–3.78 (m, 4 H, OCH2CH2N),
3.75–3.64 (m, 4 H, OCH2CH2N). 13C NMR: δ = 163.7, 148.2,
147.5, 145.8, 143.7, 67.1, 47.9, 43.2. IR (νmax/cm−1): 2971,
1636, 1393, 1066, 668, 654. HRMS-TOF (m/z): [M + H]+ calcd
200.0591, found 200.0599.
Lipophilic ligands
All the lipophilic ligands should have been dissolved in TPH to
a preferable concentration of 0.1 mol L−1. But due to their low
solubility, ligands 11 and 13 had been dissolved in a mixture of
6-Chloro-N,N-dioctylpyrazine-2-carboxamide (18). To a sol-
ution of acid chloride 16 (10 mmol) in dry CH2Cl2 (50 mL) was
1-octanol and toluene to a concentration of 0.05 mol L−1
.
added dropwise
a solution of di-n-octylamine (3.0 mL,
The obtained organic solvent was contacted with nitric acid of
variable concentrations (0.01–4 mol L−1) containing traces of
Am(III) and Eu(III). Nitric acid solutions were prepared by dilut-
ing concentrated nitric acid (Merck KGa, Darmstadt, Germany)
with ultrapure water (resistivity, 18 MΩ cm). The acidity was
checked by titration with NaOH.
10 mmol) and Et3N (3.0 mL, 20 mmol) in dry CH2Cl2 (50 mL).
The resulting mixture was stirred overnight and then all the vola-
tiles were removed in vacuo. The residue was partitioned
between H2O (30 mL) and EtOAc (70 mL). The organic phase
was dried over Na2SO4 and the solvent was removed in vacuo,
1
to afford 18 in quantitative yield as a yellow oil. H NMR: δ =
8.80 and 8.62 (s, 1 H, PyzH), 3.48 and 3.32 (t, 2 H, J = 7.5 Hz,
CH2N), 1.65–1.55 (m, 4 H, AlkH), 1.39–1.15 (m, 20 H, AlkH),
0.88–0.78 (m, 6 H, CH3). 13C NMR: δ = 162.8, 148.1, 147.3,
144.9, 143.5, 32.0, 31.9, 29.6, 29.5, 29.4, 29.3, 29.0, 27.3, 26.5,
23.0, 22.6, 21.3, 14.1. IR (νmax/cm−1): 2927, 2854, 1632, 1558,
1541, 1507, 669. HRMS-TOF (m/z): [M + H]+ calcd 382.2625,
found 382.2632.
Water-soluble ligands
All the aqueous solutions were prepared by dissolution of
weighted amounts of the ligand in ultrapure water (resistivity, 18
MΩ cm) containing 0.5 mol L−1 NH4NO3 (salting-out agent).
The initial pH of the aqueous phase was adjusted using
ammonia or diluted nitric acid. The organic solvent consisted of
0.2 mol L−1 TODGA (extractant) and 5 vol% 1-octanol dis-
solved in TPH. The organic phase was not loaded with Am and
Eu followed by stripping as TODGA extracts significant
amounts of HNO3 which would prevent obtaining reasonable
6-(Diphenylphosphoryl)-N,N-dioctylpyrazine-2-carboxamide
(20). A solution of the crude phosphine 19 (2.23 g, 5 mmol)
and H2O2 (30% aqueous, 0.8 mL) in acetone (25 mL) was
stirred for 12 h and then 1 M HCl (10 mL) was added. After
5450 | Org. Biomol. Chem., 2012, 10, 5443–5451
This journal is © The Royal Society of Chemistry 2012

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20 K. Damian, M. L. Clarke and C. J. Cobley, Appl. Organomet. Chem.,
2009, 23, 272–276.
21 M. C. Kohler, T. V. Grimes, X. Wang, T. R. Cundari and R. A. Stockland,
Organometallics, 2009, 28, 1193–1201.
22 H. H. Dam, D. N. Reinhoudt and W. Verboom, Chem. Soc. Rev., 2007,
36, 367–377.
23 Z. Kolarik, Chem. Rev., 2008, 108, 4208–4252.
results at pH > 1 without using a buffer. Instead, each of the
aqueous phases (500 μL) was spiked with the radiotracers and
contacted with the organic solvent (500 μL). The acidities of the
initial aqueous solutions were determined using a 691 Metrohm
pH meter (3 mol L−1 KCl).
24 F. W. Lewis, M. J. Hudson and L. M. Harwood, Synlett, 2011, 2609–
2632.
25 M. Iqbal, J. Huskens, M. Sypula, G. Modolo and W. Verboom, New
J. Chem., 2011, 35, 2591–2600.
Acknowledgements
26 M. Galletta, L. Baldini, F. Sansone, F. Ugozzoli, R. Ungaro, A. Casnati
and M. Mariania, Dalton Trans., 2010, 39, 2546–2553.
The authors gratefully acknowledge the financial support from
the EU ACSEPT (Actinide reCycling by SEParation and Trans-
mutation) project (FP7 collaborative project 211267).
27 See e.g. (a) E. Makrlίk, P. Vaňura, P. Selucký, V. A. Babain and
I. V. Smirnov, J. Radioanal. Nucl. Chem., 2010, 284, 629–633;
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R. Ungaro, K. Liger and J.-F. Dozol, Eur. J. Org. Chem., 2005, 2338–
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and A. Casnati, Eur. J. Org. Chem., 2010, 2675–2686; (e) R. Wietzke,
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