Separation of lanthanides and actinides using magnetic silica particles bearing covalently attached tetra-CMPO-calix[4] arenes

Article abstract of DOI:10.1039/b405602g

Calix[4]arene tetraethers in the cone conformation bearing four -NH-CO-CH₂-P(O)Ph₂ (= CMPO) residues on their wide rim and one, two or four ω-amino alkyl residues of various lengths at the narrow rim were synthesized. Reaction with dichlorotriazinyl (DCT) functionalized magnetic particles led to complete coverage of the available surface by covalently linked CMPO-calix[4]arenes in all cases. Magnetically assisted removal of Eu(III) and Am(III) from acidic solutions was distinctly more efficient with these particles in comparison to analogous particles bearing the same amount of analogous single-chain CMPO-functions. The best result, an increase of the extraction efficiency by a factor of 140-160, was obtained for attachment via two propyl spacers. The selectivity Am/Eu was in the range of 1.9-2.8. No decrease of the extraction ability was observed, when the particles were repeatedly used, after simple back extraction with water.

Full text of DOI:10.1039/b405602g

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A R T I C L E
Separation of lanthanides and actinides using magnetic silica
particles bearing covalently attached tetra-CMPO-calix[4]arenes
Volker Böhmer,a Jean-François Dozol,c Cordula Grüttner,b Karine Liger,c
Susan E. Matthews,†a Sandra Rudershausen,b Mohamed Saadiouia and Pingshan Wang‡a
a
Fachbereich Chemie und Pharmazie, Abteilung Lehramt Chemie, Johannes Gutenberg-
Universität, Duesbergweg 10-14, D-55099 Mainz, Germany
Micromod Partikeltechnologie GmbH, Friedrich-Barnewitz-Str. 4, D-18119 Rostock, Germany
CEA Cadarache/DED/SEP, F-13108 Saint Paul Lez Durence Cedex, France
b
c
Received 16th April 2004, Accepted 25th June 2004
First published as an Advance Article on the web 27th July 2004
Calix[4]arene tetraethers in the cone conformation bearing four –NH–CO–CH2–P(O)Ph2 (= CMPO) residues on their wide
rim and one, two or four -amino alkyl residues of various lengths at the narrow rim were synthesized. Reaction with
dichlorotriazinyl (DCT) functionalized magnetic particles led to complete coverage of the available surface by covalently
linked CMPO-calix[4]arenes in all cases. Magnetically assisted removal of Eu(III) and Am(III) from acidic solutions was
distinctly more efficient with these particles in comparison to analogous particles bearing the same amount of analogous
single-chain CMPO-functions. The best result, an increase of the extraction efficiency by a factor of 140–160, was
obtained for attachment via two propyl spacers. The selectivity Am/Eu was in the range of 1.9–2.8. No decrease of the
extraction ability was observed, when the particles were repeatedly used, after simple back extraction with water.
study we have varied the length and the number of linkers between
Introduction
the calixarene and the particle surface to optimise the extraction
The recovery of actinides from liquid nuclear wastes, generated
capacity of magnetic silica particles coated with tetra-CMPO
as a result of the nuclear fuel cycle, and the development and
calix[4]arenes.
production of nuclear weapons, is an area of world-wide concern.
Current approaches are based on the TRUEX process which utilises
the highly efficient, neutral, organophosphorus ligand octyl phenyl
Syntheses
N,N-diisobutyl carbamoylmethyl phosphine oxide (CMPO).1
Previously, we have reported calix[4]arene based extractants
bearing four CMPO groups at the wide2,3 or narrow rim.4 Such pre-
organisation of the chelating functions leads to a drastic increase2
of the extraction efficiency (>100 fold) combined with an enhanced
selectivity for actinides and lighter lanthanides.5–7
4,6-Dichloro-1,3,5-triazin-2-yl (DCT) functionalized magnetic
particles14 were chosen to attach the ligands by reaction with amino
groups, as outlined in Scheme 1.
This requires calix[4]arenes 1–3, bearing four CMPO-functions
on their wide rim and aminoalkyl groups at the narrow rim. Here
we varied the number of these linkers (one, two and four) as well as
their length. The synthetic pathway is exemplified in Scheme 2 for
the 1,3-derivatives 2a–c.
Solvent extraction methods using either simple extractants or
highly efficient systems such as calix[4]arene based ligands, need
very sophisticated facilities to be implemented for the recovery
of actinides from high activity wastes. However, reprocessing
operations or, more generally, nuclear facilities generate medium
activity wastes bearing actinides for which solvent extraction is not
adapted because it is too complex in its implementation. Recently
interest has focused on the use of magnetic fluidised bed separation
technology and the development of magnetically assisted chemical
separation (MACS) systems for nuclear waste remediation.8 These
techniques avoid the use of large volumes of organic solvent, but
combine the selectivity of solvent extraction with improved phase
separation in the magnetic field, resulting in a system providing
only a small volume of high level waste. The magnetic particles
can be directly vitrified or stripped, to enable their re-use in an
automated process. Particles coated with a solution of CMPO in
tri-n-butylphosphate (TBP) have been prepared by treatment of
crosslinked acrylamide particles with CMPO/TBP using hexane or
ethanol as volatile diluent.9–12
Starting with the known 1,3-dipropylether of tert-butylcalix-
[4]arene (5) the remaining hydroxyl groups were alkylated with
-bromoalkyl-phthalimides in DMF at r.t. using NaH as base.
Yields of the pure product in the cone conformation (6a–c)15
range between 50–65% since the formation of partial cone and
1,3-alternate conformers cannot be entirely avoided. The required
-bromoalkylphthalimides (commercially available for n = 3)
were obtained with yields of 70% by alkylation of phthalimide
with an excess of the respective ,-dibromoalkane (n = 5, 10)
and chromatographic work up. The following steps, ipso-nitration
of the tetra-ether derivatives (100% HNO3, CH2Cl2, rt, 90% of
7a–c), reduction of the nitro groups (SnCl2/ethanol, 90% of 8a–c)
and acylation of the so-formed amino functions by the active ester
(p-nitrophenyl(diphenylphosphoryl)acetate, 70–75% of 9a–c)
were done in close analogy to similar examples.2,3 Cleavage of
the phthalimide groups by hydrazine in refluxing ethanol finally
led with yields of 85–95% to the wide rim tetra-CMPOs 2a–c,
functionalized by two aminoalkyl groups at their narrow rim.
Tetra-CMPO calixarenes bearing one aminopentyl group (1)
or four aminopropyl groups (3) at the narrow rim were synthe-
sised analogously in three steps from the tetra-ethers 14 and 17,
respectively. 17 was directly obtained by O-alkylation of tert-
butylcalix[4]arene (70%), while 10 should be available in two
steps from tert-butylcalix[4]arene either via the syn-tripropylether
or via the monoether formed with N-bromopentylphthalimide.
However, having the monopropylether at hand a mixed 1,3-di-
ether was prepared with N-bromopentylphthalimide (40%) which
finally was exhaustively O-alkylated with propylbromide to yield
14 (51%).
As recently reported our approach is based on the covalent
attachment of CMPO derivatives on the surface of functionalised
magnetic particles.13 Such chemically modified particles should
show increased long-term stability as the ligands cannot be
desorbed or leached. In addition, this covalent attachment takes
advantage of the pre-organisation of the CMPO chelating sites on
various (macrocyclic) platforms like calix[4]arenes. In the present
† Present address: School of Chemical Sciences and Pharmacy, University
of East Anglia, Norwich, UK NR4 7TJ.
‡ Present address: CMDR of Goodyear Polymer Center, Akron University,
Akron, OH 44325-4717, USA.
T h i s j o u r n a l i s
©
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 2 7 – 2 3 3 4
2 3 2 7

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Scheme 1
Scheme 2
Model compounds 4a,b, consisting of a single CMPO-substituted
Magnetic silica particles were prepared by encapsulation of iron
aromatic unit were prepared in four steps from p-nitrophenol by
O-alkylation with the respective bromoalkylphthalimide (85% of
18a,b), reduction of the nitro groups to 19a,b, N-acylation with
the active ester (70–75% of 20a,b) and finally, cleavage of the
phthalimide by hydrazine (80–85% of 4a,b).
oxide into highly porous silica particles followed by introduction of
amino groups on the particle surface. These primary aliphatic amino
groups were derivatised with cyanurchloride to provide DCT groups
on the particle surface. For the attachment of aminofunctionalised
calix[4]arenes 1–3 and model compounds 4 according to Scheme 1
2 3 2 8
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 2 7 – 2 3 3 4

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Table 1 Extraction of europium and americium by magnetic particles with covalently bound ligands 1–4
Compound
Number of linkers
Spacer length
KD(Eu)/ml g−1
KD(Am)/ml g−1
KD(Am)/KD(Eu)
n = m + 2
1
z = 1
z = 2
z = 2
z = 2
z = 4
z = 1
z = 1
n = 5
n = 3
n = 5
n = 10
n = 3
n = 3
n = 5
121
253
130
58
69
1.6
16
226
549
310
132
193
3.8
1.87
2.17
2.38
2.28
2.80
2.38
1.63
2a
2b
2c
3
4a
4b
26
Extraction conditions: 3 M HNO3 + 152Eu + 241Am; volume of aqueous phase: 10 ml; mass of particles: 300 mg; stirring time: 1 h; T = 25 °C.
nS = (cL,0 − cL)·VL
this leads to
c
L,0 −cL
(
)
i
VL
mS
KD
=
cL
Due to saturation phenomena, these KD values are usually not
constant and thus only values obtained under identical conditions
(concentration in the liquid phase, amount of solid phase) should be
compared. Therefore the distribution coefficients KD for Eu andAm
extraction with magnetic particles coated by 1–4 were determined
under constant conditions, shaking 300 mg magnetic particles
(mS) with 10 ml (VL) Eu and Am containing test solution of known
activity (cL,0) for one hour at room temperature. After magnetic
separation of the particles the final radionuclide activity (cL) was
measured in the supernatant.
The results of the extraction experiments are summarized in
Table 1. Since the amount of calixarene fixed to the surface is iden-
tical for all the calix[4]arene based particles 1–3, and the amount of
CMPO-functions is even slightly larger for particles with 4, these
KD values can be directly compared. The following trends/effects
can be observed:
a) The extraction is much more efficient with particles coated
by calix[4]arene derivatives than for particles coated by the model
compounds 4. With a factor of >100 this is most pronounced
for 2a in comparison to 4a (both with n = 3). Thus, it is clearly
advantageous to pre-organize the CMPO-functions on a common
platform (not necessarily a calix[4]arene), and to attach this pre-
organised assembly to the particle surface.
b) The length of the spacer is obviously most crucial for the
“monomeric” CMPOs 4 where KD increases by a factor of ~10
in going from n = 3 to n = 5. This can be understood, assuming
that a certain “mobility” of the CMPO-functions on the surface is
necessary to allow the co-operative interaction of three bidentate
ligating groups with a Eu3+ or Am3+ cation.17 On the other hand,
in the series 2a–c a steady decrease of KD is observed if the length
of the two spacers increases from 3 over 5 to 10. However, this
decrease occurs on a much higher extraction level, since four
CMPO-functions are already pre-organized at the calix[4]arene
platform. These four CMPO-functions do not necessarily complex
a single cation. NMR relaxation time (T1) studies of Gd3+ complexes
of wide rim tetra-CMPOs suggest the formation of polymeric
species under anhydrous conditions, in contrast to narrow rim
tetra-CMPOs,18 and oligomeric species might be involved also in
liquid/liquid extraction. Thus, a comparison of particles coated with
2 or 4 concerns various factors and a tentative explanation for the
opposite effect caused by changes in the spacer length would be
merely speculative at the moment.
c)An indication of the optimum number of linkers (with the same
length) can be obtained by comparison of 1 with 2b and 2a with 3,
respectively. The first pair suggests that there is not much differ-
ence between a one and a two point attachment, while the second
pair indicates a stronger decrease of KD for a four point attachment.
This could be understood to be due to an unfavourable distortion of
the calix[4]arene conformation when fixed to the surface via four
linkers.
these DCT functionalised magnetic silica particles were suspended
in chloroform and shaken at room temperature in the presence of
a stoichiometric quantity of triethylamine to neutralize/capture the
hydrogen chloride. The amount of CMPO-calixarene bound to the
surface in this step was determined by monitoring its disappearance
from the liquid phase by UV-spectrometry. Thus, it was found, that
for all calix[4]arenes (25 ± 3) mol g−1 were bound to the magnetic
particles. This result is surprising since obviously there is no measur-
able influence either of the number of linkers (one, two or four in
compounds 1–3) or of the length of the spacer (3, 5 and 10 C-atoms
in 2a–c). The available surface of the particles, determined by the
BET-method,16 is 3.3 × 1019 nm2 g−1. This leads to an average area
of 2.2 nm2 per calix[4]arene molecule which corresponds more or
less exactly to the area estimated by molecular modelling. Therefore
we can conclude that the surface is completely covered by densely
packed calix[4]arenes which correlates with the observation that
the number and the length of the linkers have no influence on the
amount of calix[4]arene attached to the surface. Similarly it could
be shown that 110 ± 5 mol g−1 of the model compounds 4a,b
were bound to the particle surface, in agreement with the fact that
four single phenolic units can be slightly closer packed than in a
calix[4]arene in the cone-conformation.
Extraction
For liquid/liquid extractions the distribution coefficient KD is
defined as
n1
V
c1
c2
1
KD
=
=
n2
V2
For solid/liquid extractions the extracted amount of substance must
be related to the mass of the solid phase.
nS
nL
nS
mS
VL
mS
KD
=
=
cL
Since the extracted amount is usually determined by its decrease in
the liquid phase
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 2 7 – 2 3 3 4
2 3 2 9

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d) Some selectivity for Am over Eu is observed in all cases and
is unaffected by alterations in spacer length or the number of points
of attachment. Interestingly the values observed of between 1.6
and 2.8 are distinctly lower than those observed for wide rim tetra-
CMPOs in liquid/liquid extractions.5
Although this was not the main goal of the present study, the
potential re-use of beads was shown in a series of five successive
extraction (Eu, 3 M HNO3)/stripping cycles with magnetic particles
bearing 2a. Generally more than 90% of Eu activity was recovered
by stripping twice with demineralised water. After five cycles the
extraction capacity decreased by 10–15%, a value which is still
within the limits of error of these small scale experiments.
in chloroform. The solution was washed twice with water and brine
and then dried. Evaporation of the solvent followed by precipitation
from chloroform/methanol gave the desired compound as a white
1
solid. Yield: 10.1 g, 68%; mp 251–253 °C; H NMR (200 MHz,
CDCl3)  7.72 (m, 4H, Phth), 7.56 (m, 4H, Phth), 7.45 (s, 2H,
OH), 7.03 (s, 4H ArH), 6.78 (s, 4H ArH), 4.30 (d, 4H, J = 13.2 Hz
ArCH2Ar), 4.09 (m, 8H, CH2N + OCH2), 3.31 (d, 4H, J = 13.2 Hz,
ArCH2Ar), 2.43 (quin, 4H, J = 7.3 Hz, CH2CH2N), 1.27 (s, 18H,
t-Bu), 0.93 (s, 18H, t-Bu); FD-MS m/z = 1022.7 (M+, 100%, calc
1022.5).
25,27-Diphthalimidopropoxy-26,28-dipropoxy-p-tert-butyl-
calix[4]arene 6a. A solution of 25,27-diphthalimidopropoxy-p-
tert-butylcalix[4]arene-26,28-diol (4.00 g, 3.92 mmol) in DMF
(60 ml) was flushed with argon, then NaH (300 mg, 11.87 mmol)
was added and the mixture stirred for 30 min. Propylbromide
(1.07 ml, 11.76 mmol) was added and the stirring continued for
2 days. The reaction was quenched with water (30 ml), the result-
ing precipitate collected by filtration, dissolved in chloroform and
washed with water, 15% HCl and brine. The solution was dried
and the solvent evaporated to give a yellow oil. Column chromato-
graphy (chloroform) finally gave a white solid. Yield: 3.55 g, 82%;
Conclusion
A complete coating of the available surface of magnetic silica
particles by covalently linked CMPO-derivatives is easily pos-
sible by aminolysis of 4,6-dichloro-1,3,5-triazin-2-yl groups.
The CMPO-coated beads may be used in magnetically assisted
extraction of lanthanides and actinides. Pre-organization of four
CMPO-groups at the wide rim of calix[4]arenes leads to much bet-
ter extraction results than the direct covalent attachment of the same
amount of analogous single CMPO-functions. The present results
suggest that the binding of wide rim tetra-CMPO calix[4]arenes via
two short spacers of three carbon atoms gives the best results in
terms of extraction efficiency.
1
mp 243–245 °C (Lit.1 241–243 °C); H NMR (200 MHz, CDCl3)
 7.81 (m, 4H, Phth), 7.69 (m, 4H, Phth), 6.92 (s, 4H, ArH), 6.54
(s, 4H ArH), 4.34 (d, 4H, J = 12.2 Hz ArCH2Ar), 4.05 (t, 4H,
J = 7.8 Hz, OCH2), 3.89 (t, 4H, J = 7.3 Hz, CH2N), 3.67 (t, 4H,
J = 7.3 Hz, OCH2CH2CH3), 3.08 (d, 4H, J = 12.7 Hz, ArCH2Ar),
2.50 (quin, 4H, J = 7.8 Hz, CH2CH2N), 1.86 (sext, 4H, J = 7.3 Hz,
CH2CH3), 1.19 (s, 18H, t-Bu), 0.89 (m, 24H, t-Bu + CH2CH3);
FD-MS m/z = 1108.2 (MH+, 100%, calc 1107.6).
Experimental
Starting materials
p-tert-Butylcalix[4]arene and its mono-3 and dipropylether19 were
prepared in analogy to the literature. The synthesis of tetraether
144 and of p-nitrophenyl(diphenylphosphoryl)acetate2,20 has been
described earlier. Compounds 8a, 9a, and 2a were described in the
electronic supplementary information of ref. 13 but are listed here
for completeness.
4,6-Dichloro-1,3,5-triazin-2-yl functionalized magnetic silica
particles (micromod, product-code: 58-39-105) were used for the
covalent attachment of CMPO-derivatives.
25,27-Diphthalimidopentoxy-26,28-dipropoxy-p-tert-
butylcalix[4]arene 6b. A suspension of the dipropylether 5 (1.8 g,
2.45 mmol) in DMF (60 ml) was stirred at room temperature for 1 h
with NaH (0.143 g, 5.96 mmol). N-(5-Bromopentyl)phthalimide
(1.75 g, 5.91 mmol) was added and the mixture was stirred for
1.5 d at room temperature. The solvent was removed under reduced
pressure, and the residue taken up with CH2Cl2 (60 ml). After wash-
ing with saturated NaCl solution (2 × 70 ml), the organic phase
was dried over MgSO4, filtered and evaporated. The residue was
triturated with methanol to yield 6b as a white solid. Yield: 1.8 g,
64%; mp 190–192 °C; 1H NMR (200 MHz, CDCl3)  7.79 (m, 4H,
Phth), 7.69 (m, 4H, Phth), 6.80 (s, 4H, ArH), 6.59 (s, 4H, ArH),
4.37 (d, 4H, ArCH2Ar), 3.74 (m, 12H, OCH2 + NCH2), 3.10 (d, 4H,
ArCH2Ar), 2.02 (m, 8H, CH2), 1.76 (m, 4H, CH2), 1.45 (m, 4H,
CH2), 1.10 (s, 18H, t-Bu), 1.00 (s, 18H, t-Bu), 0.95 (t, 6H, CH3).
Synthesis of calixarenes and model compounds
N-(5-Bromopentyl)phthalimide. 1,5-Dibromopentane (20 ml,
0.140 mol), phthalimide (4.29 g, 0.028 mol) and K2CO3 (8.57 g,
0.059 mol) were added to DMF (70 ml) and stirred for 3 days under
argon. The mixture was filtered and the solvent and excess reagent
were removed under vacuum. The resulting brown oil was puri-
fied by column chromatography (CH2Cl2/hexane 4:1) to afford a
white solid. Yield: 6.27 g, 73%; mp 85–87 °C; 1H NMR (200 MHz,
CDCl3)  7.83 (m, 2H, Phth), 7.79 (m, 2H, Phth), 3.66 (t, J = 7.1,
2H, NCH2), 3.33 (t, J = 6.8, 2H, CH2Br), 1.84 (m, 2H, NCH2CH2),
1.69 (m, 2H, CH2CH2Br), 1.41 (m, 2H, CH2CH2CH2Br).
25,27-Diphthalimidodecyloxy-26,28-dipropoxy-p-tert-butyl-
calix[4]arene 6c. Prepared as described for 6b and isolated as
1
an oil. Yield: 50%; H NMR (400 MHz, CDCl3)  7.78 (m, 4H,
Phth), 7.66 (m, 4H, Phth), 6.77 (s, 4H, ArH), 6.70 (s, 4H, ArH),
4.38 (d, 4H, ArCH2Ar), 3.78 (t, 8H, OCH2), 3.64 (t, 4H, NCH2),
3.08 (d, 4H, ArCH2Ar), 1.98 (m, 8H, CH2), 1.64 (m, 4H, CH2),
1.29 (m, 24H, CH2), 1.06 (s, 18H, t-Bu), 1.01 (s, 18H, t-Bu), 0.94
(t, 6H, CH3).
N-(10-Bromodecyl)phthalimide. 1,10-Dibromodecane (40 g,
0.133 mol), phthalimide (6.18 g, 0.042 mol) and K2CO3 (9.6 g,
0.069 mol) were dissolved in DMF (280 ml) and stirred at room
temperature for 5 days. The precipitate was filtered off and the
solvent was removed under vacuum. The product was purified
by column chromatography (hexane followed by CH2Cl2) and
5,11,17,23-Tetranitro-25,27-diphthalimidopropoxy-26,28-
dipropoxycalix[4]arene 7a. Trifluoroacetic acid (2.4 ml, 31 mM)
was added to a solution of 6a (3.0 g, 2.71 mmol) in dichloromethane
(60 ml). Fuming nitric acid (2.3 ml, 5.5 mmol) was then added to the
solution. After 30 min the solution was poured onto ice and diluted
with 50 ml of dichloromethane. The organic layer was separated,
washed with water (4 times) and brine (3 times), dried and the sol-
vent was evaporated. Precipitation from dichloromethane/methanol
gave a yellow solid which was purified by column chromatography
(chloroform/methanol 30:1) to give the desired 7a. Yield: 1.63 g,
1
obtained as white crystals. Yield: 10.7 g, 70%; mp 63–65 °C; H
NMR (200 MHz, CDCl3)  7.85–7.80 (m, 2H, Phth), 7.70–7.66 (m,
2H, Phth), 3.66 (t, J = 7.0 Hz, 2H, CH2N), 3.38 (t, J = 7.0 Hz, 2H,
BrCH2), 1.89–1.75 (m, 2H, CH2), 1.73–1.60 (m, 2H, CH2), 1.26
(br s, 12H, CH2).
25,27-Diphthalimidopropoxy-p-tert-butylcalix[4]arene-
26,28-diol. p-tert-Butylcalix[4]arene (10 g, 15.4 mmol) and K2CO3
(2.34 g, 17 mmol) were heated at reflux for 1 h in acetonitrile
(380 ml). N-(3-Bromopropyl)phthalimide (9.1 g, 33.9 mmol) was
then added and the mixture heated at reflux for a further 48 h. The
solvent was then evaporated in vacuo and the residue re-dissolved
1
65%; mp 163–167 °C (Lit.1 169–171 °C); H NMR (200 MHz,
CDCl3)  7.82 (m, 4H, Phth), 7.72 (m, 4H, Phth), 7.59 (s, 4H, ArH),
7.48 (s, 4H ArH), 4.50 (d, 4H, J = 14.2 Hz ArCH2Ar), 4.11 (t, 4H,
J = 7.1 Hz, OCH2), 3.93 (t, 4H, J = 7.3 Hz, CH2N), 3.83 (t, 4H,
J = 7.1 Hz, OCH2CH2CH3), 3.38 (d, 4H, J = 13.6 Hz, ArCH2Ar),
2 3 3 0
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 2 7 – 2 3 3 4

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2.50 (quin, 4H, J = 7.1 Hz, CH2CH2N), 1.86 (sext, 4H, J = 7.3 Hz,
CH2CH3), 0.94 (t, 6H, J = 7.3 Hz, CH2CH3); FD-MS m/z = 1062.7
(M+, 100%, calc 1062.3).
acetate (2.54 g, 6.66 mmol) was added to a solution of tetraamine
8a (1.05 g, 1.11 mmol) in toluene (30 ml). The mixture was
heated to 50 °C for 18 h. The solvent was then evaporated and the
residue re-dissolved in dichloromethane. The solution was washed
repeatedly with 10% NaOH, dried and the solvent evaporated.
Column chromatography (chloroform/methanol 30:1) followed by
precipitation from dichloromethane/diethylether gave the desired
compound as a white solid. Yield: 1.43 g, 68%; mp 179–182 °C;
Rf = 0.53 (chloroform/methanol 9:1); 1H NMR (200 MHz,
DMSO-d6)  9.77 (s, 2H, NH), 9.34 (s, 2H, NH), 7.43–7.84 (m,
48H, Phth + Ph2P), 6.93 (s, 4H,ArH), 6.39 (s, 4HArH), 4.23 (d, 4H,
J = 12.7 Hz ArCH2Ar), 3.93 (m, 4H, OCH2), 3.59–3.76 (m, 16H,
OCH2CH2CH3 + CH2N + POCH2CO), 3.00 (d, 4H, J = 13.2 Hz,
ArCH2Ar), 2.12 (m, 4H, CH2CH2N), 1.66 (m, 4H, CH2CH3), 0.83
(t, 6H, J = 7.0 Hz, CH2CH3); FD-MS m/z = 1911.9 (MH+, calc
1911.6).
5,11,17,23-Tetranitro-25,27-diphthalimidopentoxy-26,28-
dipropoxycalix[4]arene 7b. Tetraether 6b (1.5 g, 1.29 mmol) was
dissolved in dry CH2Cl2 (60 ml) at room temperature and mixed
with 13 ml glacial acetic acid. Nitric acid (100%, 4 ml) was added
dropwise with stirring. After 3.5 h, when the colour of the solution
had changed from black-violet to orange-yellow, water was added
and stirring continued for 1 h. The organic phase was separated,
neutralized with sodium carbonate solution, washed with brine,
dried (MgSO4) and evaporated. The residue was dissolved in the
smallest amount of CHCl3, methanol was added, and the crude
product precipitated as a nearly white powder. Yield: 1.28 g, 89%;
mp 162–165 °C; 1H NMR (200 MHz, CDCl3): 7.79 (m, 4H, Phth),
7.72 (m, 4H, Phth), 7.65 (s, 4H, ArH), 7.40 (s, 4H, ArH), 4.49 (d,
4H, ArCH2Ar), 3.93 (t, 8H, OCH2), 3.69 (t, 4H, NCH2), 3.38 (d,
4H, ArCH2Ar), 1.88 (m, 8H, CH2), 1.74 (m, 4H, CH2), 1.44 (m, 4H,
CH2), 0.97 (t, 6H, CH3).
5,11,17,23-Tetra-CMPO-25,27-diphthalimidopropoxy-26,28-
dipentoxycalix[4]arene 9b. p-Nitrophenyl(diphenylphosphoryl)-
acetate (0.8 g, 2.1 mmol) was stirred with 8b (0.35 g, 0.35 mmol) in
CHCl3 (25 ml) containing 0.2 g of triethylamine for 18 h.Additional
CHCl3 (10 ml) was added, the solution was washed repeatedly with
10% aq. NaOH, dried and the solvent evaporated. The residue was
further purified by column chromatography (CHCl3/methanol)
and precipitation from CHCl3/hexane to give a pale yellow
powder. Yield: 1.13 g, 72%; mp 165–167 °C; 1H NMR (400 MHz,
DMSO-d6): 9.50 (s, 2H, CONH), 9.41 (s, 2H, CONH), 7.69 (m, 24H,
Ph2P + Phth), 7.43 (m, 24H, Ph2P), 6.62 (s, 4H, ArH), 6.53 (s, 4H,
ArH), 4.14 (d, 4H, ArCH2Ar), 3.61 (m, 16H, COCH2PO + OCH2),
3.50 (t, 4H, NCH2), 2.90 (d, 4H, ArCH2Ar), 1.69 (m, 8H, CH2), 1.56
(m, 4H, CH2), 1.31 (m, 4H, CH2), 0.81 (t, 6H, CH3).
5,11,17,23-Tetranitro-25,27-diphthalimidodecyloxy-26,28-
dipropoxycalix[4]arene 7c. Prepared as described for 7b. Yield:
87%; mp 169–170 °C; 1H NMR (400 MHz, CDCl3): 7.78 (m, 4H,
Phth), 7.68 (m, 4H, Phth), 7.57 (s, 4H,ArH), 7.51 (s, 4H,ArH), 4.49
(d, 4H, ArCH2Ar), 3.93 (m, 8H, OCH2), 3.63 (t, 4H, NCH2), 3.38
(d, 4H, ArCH2Ar), 1.88 (m, 12H, CH2), 1.63 (m, 4H, CH2), 1.29 (m,
24H, CH2), 0.97 (t, 6H, CH3).
5,11,17,23-Tetraamino-25,27-diphthalimidopropoxy-26,28-
dipropoxycalix[4]arene 8a. SnCl2·H2O (6.6 g) was added to a
suspension of 7a (1.5 g, 1.41 mmol) in ethanol (40 ml) and heated
at reflux for 18 h. The mixture was poured onto ice water, diluted
with dichloromethane (300 ml) and stirred for 1 h. 1 M NaOH
(300 ml) was then added and stirring continued for 1 h. The organic
layer was separated and washed with water and brine. After drying
the solvent was evaporated to give the amine as a pale brown foam.
5,11,17,23-Tetra-CMPO-25,27-diphthalimidopropoxy-26,28-
didecyloxycalix[4]arene 9c. Prepared as described for 9b. Yield:
1
75%; mp 150–152 °C; H NMR (400 MHz, CDCl3): 8.91 (s, 2H,
CONH), 8.85 (s, 2H, CONH), 7.77 (m, 24H, Ph2P + Phth), 7.43
(m, 24H, Ph2P), 6.57 (s, 4H, ArH), 6.48 (s, 4H, ArH), 4.29 (d, 4H,
ArCH2Ar), 3.71 (m, 8H, CH2), 3.63 (t, 4H, NCH2), 3.40 (d, 8H,
COCH2PO), 3.01 (d, 4H, ArCH2Ar), 1.77 (m, 8H, CH2), 1.63 (m,
4H, CH2), 1.23 (m, 24H, CH2), 0.85 (t, 6H, CH3).
1
Yield: 1.19 g, 89%; H NMR (200 MHz, DMSO)  7.80 (m, 8H,
Phth), 6.12 (s, 4H, ArH), 5.73 (s, 4H ArH), 4.3 (b, 4H, NH2), 4.10
(d, 4H, J = 12.7 Hz ArCH2Ar), 3.83 (t, 4H, J = 7.8 Hz, OCH2); 3.64
(t, 4H, J = 6.8 Hz, CH2N), 3.45 (t, 4H, J = 7.3 Hz, OCH2CH2CH3),
2.75 (d, 4H, J = 12.7 Hz, ArCH2Ar), 2.28 (m, 4H, J = 7.1 Hz,
CH2CH2N), 1.66 (m, 4H, J = 7.3 Hz, CH2CH3), 0.79 (t, 6H,
J = 7.3 Hz, CH2CH3); FD-MS m/z = 942.8 (M+, 100%, calc 942.4).
5,11,17,23-Tetra-CMPO-25,27-bis(aminopropoxy)-26,28-
dipropoxycalix[4]arene 2a. Hydrazine hydrate (1.48 ml) was
added to a suspension of 300 mg (0.16 mmol) of 9a in ethanol
(10 ml). The mixture was heated to reflux for 1 h and the solvent
evaporated. The residue was re-dissolved in a mixture of dichloro-
methane and water. The aqueous layer was then separated and
washed four times with dichloromethane. The combined organic
layers were then washed with brine and the solvent evaporated to
give a light yellow foam. Yield: 254 mg, 96%; mp 207–212 °C
(slow decomp.); 1H NMR (200 MHz, DMSO-d6)  9.68 (s, 2H, NH),
9.47 (s, 2H, NH), 7.45–7.82 (m, 40H, Ph2P), 6.80 (s, 4H, ArH), 6.54
(s, 4H ArH), 4.25 (d, 4H, J = 13.2 Hz ArCH2Ar), 3.62–3.78 (m,
16H, OCH2CH2CH3 + POCH2CO + OCH2CH2NH2), 3.50 (br, 8H,
NH2), 3.01 (d, 4H, J = 13.2 Hz, ArCH2Ar), 2.72 (t, 4H, J = 6.8 Hz,
CH2N), 1.85 (m, 8H, CH2CH3 + CH2CH2N), 0.88 (t, 6H, J = 7.3 Hz,
CH2CH3).
5,11,17,23-Tetraamino-25,27-diphthalimidopropoxy-26,28-
dipentoxycalix[4]arene 8b. Calixarene 7b (0.95 g, 0.85 mmol) was
heated under reflux with SnCl2·H2O (3.2 g, 4.5 mol per mol NO2)
in ethanol/dioxane (1:1; 40 ml) for 10 h. NaOH (10%) was then
added and the stirring continued for additional 1 h. The aqueous so-
lution was extracted with CH2Cl2 (2 × 70 ml) and the organic phase
was washed with brine and water, dried (MgSO4) and evaporated.
Precipitation from CHCl3/hexane gave 8b as a pale yellow powder.
Yield: 0.76 g, 90%; mp 155–156 °C; 1H NMR (200 MHz, CDCl3):
7.79 (m, 4H, Phth), 7.66 (m, 4H, Phth), 6.07 (s, 4H, ArH), 5.95 (s,
4H, ArH), 4.27 (d, 4H, ArCH2Ar), 3.68 (t, 8H, OCH2), 3.17 (t, 4H,
NCH2), 2.90 (d, 4H, ArCH2Ar), 1.84 (m, 8H, CH2), 1.44 (m, 8H,
CH2), 0.97 (t, 6H, CH3).
5,11,17,23-Tetra-CMPO-25,27-bis(aminopentyloxy)-26,28-
dipropoxycalix[4]arene 2b. Hydrazine hydrate (1.4 ml) was
added to a solution of 9b (0.2 g) in ethanol (15 ml) and the mixture
refluxed for 2 h. After evaporation the residue was dissolved in
a mixture of CH2Cl2 and water. The aqueous layer was extracted
three times with CH2Cl2, the combined organic layers were then
washed with brine, dried with MgSO4 and evaporated to give 2b
as a white solid. Yield: 0.15 g, 89%; mp 187–190 °C; (Found: C,
69.27; H, 6.49; N, 5.02; C100H106N6O12P4·H2O requires C, 69.59;
5,11,17,23-Tetraamino-25,27-diphthalimidopropoxy-26,28-
didecyloxycalix[4]arene 8c. Prepared as described for 8b. Yield:
87%; 154–157 °C; 1H NMR (400 MHz, CDCl3): 7.78 (m, 4H, Phth),
7.67 (m, 4H, Phth), 6.06 (s, 4H, ArH), 5.96 (s, 4H, ArH), 4.28 (d,
4H, ArCH2Ar), 3.67 (m, 12H, NCH2 + OCH2), 3.10 (b, 8H, NH2),
2.88 (d, 4H, ArCH2Ar), 1.81 (m, 12H, CH2), 1.63 (m, 4H, CH2), 1.5
(m, 24H, CH2), 0.88 (t, 6H, CH3).
1
H 6.31; N 4.87%). H NMR (400 MHz, DMSO-d6): 9.45 (b, 4H,
5,11,17,23-Tetra-CMPO-25,27-diphthalimidopropoxy-26,28-
dipropoxycalix[4]arene 9a. p-Nitrophenyl(diphenylphosphoryl)-
CONH), 7.71–7.43 (m, 40H, Ph2P), 6.61 (b, 8H, ArH), 4.21 (d,
4H, ArCH2Ar), 3.64 (b, 16H, COCH2PO + OCH2), 2.97 (d, 4H,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 2 7 – 2 3 3 4
2 3 3 1

View Article Online
ArCH2Ar), 2.50 (m, 4H, NCH2), 1.74 (m, 8H, CH2), 1.37 (m, 8H,
CH2), 0.89 (t, 6H, CH3).
(MgSO4) and evaporated. The residue was precipitated from
CHCl3/hexane to give 12 as a light yellow powder. Yield: 0.71 g,
81%; mp 155–158 °C; 1H NMR (400 MHz, CDCl3): 7.83 (m, 2H,
Phth), 7.72 (m, 2H, Phth), 6.06 (s, 4H, ArH), 6.05 (s, 2H, ArH),
6.03 (s, 2H, ArH), 4.32, 4.29 (2 × d, 4H, ArCH2Ar), 3.80–3.70 (m,
10H, NCH2 + OCH2), 3.14 (br s, 8H, NH2), 2.93 (d, 4H, ArCH2Ar),
1.90–1.81 (m, 8H, CH2), 1.78–1.71 (m, 2H, CH2), 1.45–1.40 (m,
2H, CH2), 0.97–0.90 (m, 9H, CH3).
5,11,17,23-Tetra-CMPO-25,27-bis(aminodecyloxy)-26,28-
dipropoxycalix[4]arene 2c. Obtained as a pale yellow powder as
described for 2b. Yield: 87%; mp 180–182 °C; (Found: C, 71.01;
H, 7.21; N, 4.76; C110H126N6O12P4·H2O requires C, 70.80; H 6.91;
N, 4.50%). 1H NMR (400 MHz, CDCl3): 8.92 (s, 2H, CONH), 8.79
(s, 2H, CONH), 7.72 (m, 16H, Ph2P), 7.39 (m, 24H, Ph2P), 6.64 (s,
4H, ArH), 6.46 (s, 4H, ArH), 4.32 (d, 4H, ArCH2Ar), 3.76 (m, 4H,
OCH2), 3.65 (b, 4H, NH2), 3.41 (m, 12H, COCH2PO + CH2), 3.02
(d, 4H, ArCH2Ar), 2.66 (t, 4H, NCH2), 1.78 (m, 8H, CH2), 1.42 (m,
4H, CH2), 1.26 (m, 24H, CH2), 0.90 (t, 6H, CH3).
5,11,17,23-Tetra-CMPO-25-phthalimidopentyloxy-26,27,28-
tripropoxycalix[4]arene 13. p-Nitrophenyl(diphenylphosphoryl)-
acetate (0.90 g) was stirred with 12 (0.30 g) in CHCl3 (25 ml)
containing triethylamine (0.1 g) for 18 h. Additional CHCl3
(10 ml) was added, the solution was washed repeatedly with 10%
aq. NaOH, dried (MgSO4) and evaporated. The pale yellow residue
was purified by column chromatography (CHCl3/methanol) and
precipitation from chloroform/hexane to give a white powder.
Yield: 0.54 g, 83%; mp 185–187 °C; 1H NMR (400 MHz, CDCl3):
8.95 (s, 4H, CONH), 7.81 (m, 2H, Phth), 7.74–7.68 (m, 16H,
Ph2P), 7.55–7.41 (m, 26H, Phth + Ph2P), 6.58 (s, 2H, ArH), 6.55
(s, 6H, ArH), 4.32, 4.29 (2 × d, 4H, ArCH2Ar), 3.81–3.68 (m, 10H,
NCH2 + OCH2), 3.45 (d, 8H, COCH2PO), 3.50 (t, 4H, NCH2), 3.05,
3.02 (2 × d, 4H, ArCH2Ar), 1.86–1.78 (m, 8H, CH2), 1.75–1.71(m,
2H, CH2), 1.42–1.38 (m, 2H, CH2), 0.94–0.87 (m, 9H, CH3).
25-Phthalimidopentyloxy-27-propoxy-p-tert-butylcalix[4]-
arene-26,28-diol. A suspension of tert-butylcalix[4]arene mono-
propylether (3.0 g, 4.38 mmol), and K2CO3 (0.42 g, 3.04 mmol)
in acetonitrile (120 ml) was stirred under reflux for 1 h. 5-
Bromopentylphthalimide (1,43 g, 4.83 mmol) was added and the
mixture was refluxed for 2.5 days. After cooling it was filtered and
evaporated. The oily residue was triturated with methanol and the
white solid finally recrystallised from CHCl3/methanol: Yield 1.7 g,
1
39%; mp 139–142 °C. H NMR (400 MHz, CDCl3): 7.76 (s, 2H,
OH), 7.70 (m, 2H, Phth), 7.60 (m, 2H, Phth), 7.01 (s, 2H,ArH), 6.99
(s, 2H, ArH), 6.83 (s, 4H, ArH), 4.25, 4.15 (2 × d, 4H, ArCH2Ar),
3.97 (t, 2H, OCH2), 3.91 (t, 2H, OCH2), 3.78 (t, 2H, NCH2), 3.30,
3.20 (2 × d, 4H, ArCH2Ar), 2.07–2.01 (m, 4H, CH2), 1.87–1.83 (m,
4H, CH2), 1.29–1.25 (m, 21H, CH3 + t-Bu), 1.00 (s, 18H, t-Bu).
5,11,17,23-Tetra-CMPO-25-aminopentyloxy-26,27,28-
tripropoxycalix[4]arene 1. Hydrazine hydrate (1.4 ml) was
heated under reflux with 13 (0.3 g) in ethanol (15 ml) for 2 h.
After evaporation the residue was dissolved in a mixture of
CH2Cl2 and water. The aqueous layer was washed three times with
CH2Cl2, the organic layers were combined, washed with brine,
dried (MgSO4) and evaporated to give 1 as a white solid. Yield:
0.25 g, 91%; mp 180–183 °C; (Found: C, 67.66; H, 6.14; N, 4.51;
25-Phthalimidopentyloxy-26,27,28-tripropoxy-p-tert-
butylcalix[4]arene 10. Asuspension of the mixed diether described
above (1.7 g, 1.88 mmol) in DMF (60 ml) was stirred at RT for 1 h
with NaH (0.122 g, 4.83 mmol). Bromopropane (0.53 g, 4.31 mmol)
was then added and the mixture was stirred for 2 d at room tem-
perature. The solvent was removed under reduced pressure, and the
residue taken up with CH2Cl2 (60 ml). After washing with brine
(2 × 40 ml), the organic phase was dried (MgSO4) and evaporated.
Trituration with methanol gave 10 as a white solid. Yield: 0.65 g,
51%; mp 160–163 °C; 1H NMR (400 MHz, CDCl3): 7.85 (m, 2H,
Phth), 7.72 (m, 2H, Phth), 6.79 (s, 4H, ArH), 6.77 (s, 2H, ArH),
6.76 (s, 2H, ArH), 4.43, 4.37 (2 × d, 4H, ArCH2Ar), 3.88–3.73 (m,
8H, NCH2 + OCH2), 3.13, 3.09 (2 × d, 4H, ArCH2Ar), 2.08–1.98
(m, 4H, CH2), 1.87–1.83 (m, 8H, CH2), 1.84–1.76 (m, 2H, CH2),
1.53–1.47 (m, 2H, CH2), 1.10 (s, 27H, t-Bu), 1.10 (s, 9H, t-Bu),
1.00 (t, 9H, CH3).
1
C98H101N5O12P4·4H2O requires C, 67.77; H, 6.33; N, 4.16%). H
NMR (400 MHz, CDCl3, 55 °C): 8.87 (s, 4H, CONH), 7.79–7.72
(m, 16H, Ph2P), 7.54–7.42 (m, 24H, Ph2P), 6.61 (s, 2H, ArH), 6.58
(s, 6H, ArH), 4.36, 4.33 (2 × d, 4H, ArCH2Ar), 3.85–3.77 (m, 8H,
OCH2), 3.45 (d, 8H, COCH2PO), 3.07 (2 × d, 4H, ArCH2Ar), 2.72
(m, 2H, NCH2), 1.91–1.80 (m, 8H, CH2), 1.53–1.49 (m, 2H, CH2),
1.42–1.38 (m, 2H, CH2), 0.97–0.93 (m, 9H, CH3).
5,11,17,23-Tetranitro-25,26,27,28-tetraphthalimidopropoxy-
calix[4]arene 15. Tetraether 14 (1.6 g) was dissolved in dry CH2Cl2
(60 ml) at room temperature and mixed with 14 ml glacial acetic
acid. Then 100% nitric acid (4.0 ml) was added dropwise with
stirring. After 4 h, when the colour of the solution had changed
from black-violet to orange-yellow, water was added and stirring
continued for 1 h. The organic phase was separated, neutralized
with sodium carbonate solution, washed with brine, dried (MgSO4),
and evaporated. The residue was dissolved in the smallest amount
of CHCl3, methanol was added to precipitate 15 as a nearly white
5,11,17,23-Tetranitro-25-phthalimidopentyloxy-26,27,28-
tripropoxycalix[4]arene 11. Tetraether 10 (1.0 g) was dissolved in
dry CH2Cl2 (60 ml) at room temperature and mixed with glacial ace-
tic acid (11 ml). Then 100% nitric acid (3.2 ml) was added dropwise
with stirring. After 4 h, when the colour of the solution had changed
from black-violet to orange-yellow, water was added and stirring
continued for 1 h. The organic phase was separated, neutralized
with Na2CO3 solution, washed with brine, dried (MgSO4) and evap-
orated. The residue was dissolved in the smallest amount of CHCl3,
methanol was added to precipitate 11 as a nearly white powder.
1
powder. Yield: 0.51 g, 53%; mp > 330 °C; H NMR (400 MHz,
CDCl3): 7.72 (m, 8H, Phth), 7.64 (m, 8H, Phth), 7.54 (s, 8H, ArH),
4.62 (d, 4H,ArCH2Ar), 4.18 (t, 8H, OCH2), 3.92 (t, 8H, NCH2), 3.45
(d, 4H, ArCH2Ar), 2.36–2.31 (m, 8H, CH2); FD-MS m/z = 1354.2
(MH+, 100%, calc 1353.4).
1
Yield: 0.5 g, 88%; mp 164–167 °C; H NMR (400 MHz, CDCl3):
7.84 (m, 2H, Phth), 7.75 (m, 2H, Phth), 7.62 (s, 2H, ArH), 7.61 (s,
2H, ArH), 7.54 (s, 2H, ArH), 7.51 (s, 2H, ArH), 4.54, 4.50 (2 × d,
4H, ArCH2Ar), 4.00–3.92 (m, 8H, OCH2), 3.72 (t, 2H, NCH2), 3.42,
3.39 (2 × d, 4H, ArCH2Ar), 1.96–1.87 (m, 8H, CH2), 1.81–1.74 (m,
2H, CH2), 1.50–1.43 (m, 2H, CH2), 1.03–0.99 (m, 9H, CH3).
5,11,17,23-Tetraamino-25,26,27,28-tetraphthalimido-
propoxycalix[4]arene 16. A solution of 15 (0.50 g) in ethanol/
dioxane (1:1, 20 ml) was heated under reflux with SnCl2·H2O
(1.38 g) for 8 h. NaOH (10%) was added and the stirring continued
for 1 h. The aqueous solution was extracted with CH2Cl2 (2 × 70 ml)
and the organic phase was washed with water and brine, dried
(MgSO4) and evaporated. Precipitation from CHCl3/hexane gave
16 as a pale yellow powder. Yield 0.36 g, 80%; mp 166–170 °C. 1H
NMR (400 MHz, CDCl3): 7.70 (m, 8H, Phth), 7.59 (m, 8H, Phth),
6.03 (s, 8H, ArH), 4.35 (d, 4H, ArCH2Ar), 3.93 (t, 8H, OCH2), 3.87
(t, 8H, NCH2), 2.97 (d, 4H, ArCH2Ar), 2.76 (broad s, 8H, NH2),
2.30–2.23 (m, 8H, CH2); FD-MS m/z = 1233.0 (MH+, 100%, calc
1233.5).
5,11,17,23-Tetraamino-25-phthalimidopentyloxy-26,27,28-
tripropoxycalix[4]arene 12. A solution of 11 (0.5 g) in ethanol/
dioxane (1:1, 35 ml) was heated under reflux for 10 h with
SnCl2·H2O (1.98 g, 4.5 mole per mole NO2). NaOH (10%) was
then added at room temperature and stirring was continued for
1 h. The aqueous solution was extracted with CH2Cl2 (2 × 50 ml)
and the organic phase was washed with water and brine, dried
2 3 3 2
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 2 7 – 2 3 3 4

View Article Online
5,11,17,23-Tetra-CMPO-25,26,27,28-tetraphthalimido-
propoxycalix[4]arene 17. p-Nitrophenyl(diphenylphosphoryl)-
acetate (0.41 g) was stirred with 16 (0.3 g, 0.24 mmol) in
chloroform (25 ml) containing 0.1 g of triethylamine for 18 h.
Additional CHCl3 (10 ml) was added, the solution was washed re-
peatedly with 10% aq. NaOH, dried (MgSO4) and evaporated.After
column chromatography (CHCl3/methanol), and precipitation from
CHCl3 17 was obtained as a pale yellow powder. Yield 0.35 g, 66%;
mp 189–192 °C; 1H NMR (400 MHz, CDCl3): 8.94 (s, 2H, CONH),
7.74–7.71 (m, 16H, Ph2P), 7.69 (m, 8H, Phth), 7.59 (m, 8H, Phth),
7.53–7.42 (m, 24H, Ph2P), 6.55 (s, 4H, ArH), 6.53 (s, 4H, ArH),
4.35 (d, 4H,ArCH2Ar), 3.96 (t, 8H, OCH2), 3.86 (t, 8H, NCH2), 3.44
(d, 8H, COCH2PO), 3.50 (t, 4H, NCH2), 3.07 (d, 4H, ArCH2Ar),
2.28–2.25 (m, 8H, CH2).
7.51–7.40 (6H, m, Ph2P), 7.29 (2H, d, J = 8.3 Hz, ArH), 6.63 (2H,
d, J = 8.3 Hz, ArH), 3.98–3.81 (4H, CH2), 3.45 (2H, d, J = 13.5 Hz,
PCH2), 2.11 (3H, t, J = 6.3 Hz, CH2).
p-(Diphenylphosphorylacetamino)phenoxypentylphtha-
limide 20b. Prepared as described for 20a using monoamine 19b.
1
Yield 75%; mp 256–257 °C; H NMR (200 MHz, CDCl3)  9.45
(1H, s,ArNH), 7.76–7.65 (8H, m, NPhtH and Ph2P), 7.51–7.40 (6H,
m, Ph2P), 7.29 (2H, d, J = 8.3 Hz, ArH), 6.63 (2H, d, J = 8.3 Hz,
ArH), 3.98–3.81 (4H, m, CH2), 3.45 (2H, d, J = 13.5 Hz, PCH2),
2.11 (3H, t, J = 6.3 Hz, CH2).
p-(Diphenylphosphorylacetamino)phenoxypropylamine
4a. Hydrazine hydrate (5.7 ml) was added to a suspension of 20a
(2.0 g, 3.71 mmol) in ethanol (40 ml). The mixture was heated to
reflux upon which the solid dissolves to give a pale yellow solu-
tion. After 1 h, the ethanol was partially removed by evaporation
and the residue dissolved in a mixture of CH2Cl2/water. The aque-
ous layer was extracted four times with CH2Cl2, the combined
organic phase was washed with aqueous Na2CO3 and brine, dried
(MgSO4) and evaporated to afford a white solid powder which was
recrystallised from hexane. Yield: 1.3 g, 86%; mp 243–245 °C;
(Found: C, 67.83; H, 6.41; N, 6.65; C23H25N2O3P requires C,
5,11,17,23-Tetra-CMPO-25,26,27,28-tetra(aminopropoxy)-
calix[4]arene 3. Hydrazine hydrate (1.4 ml) was heated under
reflux with 17 (0.2 g) in ethanol (15 ml) for 2 h. The residue ob-
tained after evaporation was dissolved in a mixture of CH2Cl2 and
water. The aqueous layer was extracted three times with CH2Cl2, the
combined organic layers were washed with brine, dried (MgSO4)
and evaporated to give 3 as a white powder. Yield: 84 mg, 55%;
1
mp 145–147 °C; H NMR (400 MHz, DMSO-d6): 9.24 (s, 4H,
1
67.64; H, 6.17; N. 6.86%). H NMR (200 MHz, CDCl3)  9.56
CONH), 7.83–7.73 (m, 16H, Ph2P), 7.52–7.46 (m, 24H, Ph2P), 6.70
(s, 8H, ArH), 4.33 (d, 4H, ArCH2Ar), 3.90 (m, 8H, OCH2), 3.86
(t, 8H, NCH2), 3.62 (d, 16H, COCH2PO), 3.28–2.76 (broad, 20H,
ArCH2Ar + NH2 + NCH2), 2.00–1.96 (m, 8H, CH2).
(1H, s, ArNH), 7.77–7.66 (4H, m, Ph2P), 7.53–7.42 (6H, m, Ph2P),
7.32 (2H, d, J = 7.8 Hz, ArH), 6.71 (2H, d, J = 8.1 Hz, ArH), 3.93
(2H, t, J = 6.5 Hz, CH2), 3.47 (2H, d, J = 13.8 Hz, PCH2), 2.83
(2H, t, J = 7.5 Hz, CH2), 2.70 (2H, b s, NH2), 1.83 (3H, t, J =
6.8 Hz, CH2).
N-3-(p-Nitrophenoxy)propylphthalimide 18a. A solution of
N-bromopropylphthalimide(9.5g, 35mmol)inacetonitrile(100 ml)
was added dropwise to a stirred suspension of p-nitrophenol (5.0 g,
35 mmol) and K2CO3 (9.6 g, 70 mmol) in acetonitrile (100 ml).
The resulting mixture was heated at reflux for 24 h. The solvent
was evaporated and the residue taken up in CH2Cl2/water. The
organic layer was washed repeatedly with an aqueous Na2CO3
solution, dried (MgSO4) and evaporated. The crude material was
purified by column chromatography (ethyl acetate) and precipitated
from CHCl3/hexane to give a white solid. Yield 9.76 g, 85%; mp
99–100 °C, 1H NMR (200 MHz, CDCl3)  8.21 (2H, d, J = 9.1 Hz,
ArH), 7.87–7.65 (4H, m, Phth), 6.87 (2H, d, J = 8.3 Hz, ArH), 4.15
(2H, t, J = 6.6 Hz, ArOCH2), 3.94 (2H, t, J = 7.2 Hz, NCH2), 2.25
(3H, t, J = 6.8 Hz, CH2).
p-(Diphenylphosphorylacetamino)phenoxypentylamine
4b. Prepared from 20b as described for 4a. Yield: 78%; mp
140–141 °C; (Found: C, 68.43; H, 6.98; N, 6.28; C25H29N2O3P
requires C, 68.79; H 6.70; N, 6.42%). 1H NMR (200 MHz, CDCl3)
 9.50 (1H, s, ArNH), 7.78–6.67 (4H, m, Ph2P), 7.51–7.42 (6H, m,
Ph2P), 7.32 (2H, d, J = 8.1 Hz, ArH), 6.72 (2H, d, J = 8.4 Hz, ArH),
3.86 (2H, t, J = 7.2 Hz, CH2), 3.46 (2H, d, J = 14.2 Hz, PCH2), 2.67
(2H, t, J = 6.7 Hz, CH2), 1.72 (2H, t, J = 7.1 Hz, CH2), 1.50–1.38
(4H, m, CH2).
Preparation of CMPO-coated magnetic particles
Covalent attachment of calix[4]arenes 1–3. 50 mol of each
of the calix[4]arenes 1–3 and 50, 100 or 200 mol triethylamine
(1 mole per mole –NH2) were dissolved in 20 ml chloroform
(solution A). 1.5 g of dry 4,6-dichloro-1,3,5-triazin-2-yl func-
tionalized magnetic silica particles (micromod, product-code:
58-39-105) were added and the particle suspensions were shaken
at room temperature for 24 h. Then the particles were separated
with a permanent magnet. The supernatant (solution B) was re-
moved and the particles were washed with chloroform by three
successive resuspension/magnetic separation cycles using 20 ml
chloroform per washing step. After the last magnetic separation
the supernatant was removed and the particles were dried in
vacuum for 8 h.
For the UV-spectroscopic determination of the calix[4]arene
concentration 20 l of solution A were diluted to 2 ml with
chloroform to reach c(calix) = 25 mol l−1. Further dilutions with
chloroform (c = 12.5, 6.25, 3.13, and 1.56 mol l−1) were used to
measure the absorption at 242 nm and to establish a calibration
curve A(242 nm) = f[c(calix)] by linear regression. 20 l of solution
B were diluted analogously to 2 ml with chloroform, the absorption
at 242 nm was measured to determine c(calix) and to calculate the
amount of calix[4]arene bound to the particles. It was checked that
the amount of calixarene in the chloroform of the first washing step
was negligible.
N-5-(p-Nitrophenoxy)pentylphthalimide 18b. Prepared as de-
scribed for 18a; yield 85%, mp 110–115 °C. 1H NMR (200 MHz,
CDCl3)  8.17 (2H, d, J = 8.2 Hz, ArH), 7.24–7.14 (4H, m, Phth),
6.91 (2H, d, J = 8.3 Hz, ArH), 4.02 (2H, t, J = 7.2 Hz, ArOCH2),
1.95–1.75 (2H, m, CH2), 1.52–1.31 (4H, m, CH2), 0.93 (3H, t,
J = 7.2 Hz, CH2).
N-3-(p-Aminophenoxy)propylphthalimide 19a. A catalytic
amount of Pd/C was added to a solution of 18a (4 g, 12.2 mmol)
in toluene. H2 gas was admitted under normal pressure and the
mixture stirred for 48 h. Filtration through a celite® bed and
evaporation gave the amine as a colourless oil in nearly quantita-
tive yield.
N-5-(p-Aminophenoxy)pentylphthalimide 19b. Prepared
analogously from 18b and both amines were used for the acylation
without further characterisation.
p-(Diphenylphosphorylacetamino)phenoxypropylphtha-
limide 20a. p-Nitrophenyl(diphenylphosphoryl)acetate (2.66 g,
7 mmol) and monoamine 19a (2.0 g, 6.75 mmol) were dissolved in
toluene (30 ml) and kept at 50 °C for 24 h. The solvent was evapo-
rated and the residue dissolved in CH2Cl2. The solution was washed
repeatedly with 10% aqueous Na2CO3, dried (MgSO4) and the sol-
vent removed in vacuo. Precipitation from CH2Cl2/hexane gave a
white solid. Yield 2.5 g, 69%; mp 210–211 °C. 1H NMR (200 MHz,
CDCl3) H 9.45 (1H, s, ArNH), 7.76–7.65 (8H, m, Phth and Ph2P),
Covalent attachment of model compounds 4. The proce-
dure for the immobilization of model compounds 4 was similar
using a solution of 200 mol of 4a,b and 200 mol triethylamine
in 20 ml chloroform for the reaction with 1.5 g of DCT functional-
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 2 7 – 2 3 3 4
2 3 3 3

View Article Online
4 S. Barboso, A. Garcia Carrera, S. E. Matthews, F. Arnaud-Neu,
V. Böhmer, J.-F. Dozol, H. Rouquette and M.-J. Schwing-Weill, J.
Chem. Soc., Perkin Trans. 2, 1999, 719–724.
ized magnetic silica particles. The UV-spectroscopic analysis was
carried out analogously at 266 nm.
5 L. H. Delmau, N. Simon, M.-J. Schwing-Weill, F. Arnaud-Neu, J.-F.
Dozol, S. Eymard, B. Tournois, V. Böhmer, C. Grüttner, C. Musigmann
and A. Tunayar, Chem. Commun., 1998, 1627–1628.
6 For CMPO-functions attached to the wide rim of cavitands see:
H. Boerrigter, W. Verboom and D. N. Reinhoudt, J. Org. Chem., 1997,
62, 7148–7155; for a rigidified calix[4]arene skeleton compare ref.
20.
7 For tripodal CMPO-derivatives see: M. W. Peters, E. J. Werner and
M. J. Scott, Inorg. Chem., 2002, 41, 1707–1716.
8 L. Nuñez and M. D. Kaminski, Chemtech, 1998, 41–44.
9 L. Nuñez, B. A. Buchholz and G. F. Vandegrift, Sep. Sci. Technol., 1995,
30, 1455–1471.
10 L. Nuñez, B. A. Buchholz, M. Kaminski, S. B. Aase, N. R. Brown and
G. F. Vandegrift, Sep. Sci. Technol., 1996, 31, 1393–1398.
11 M. D. Kaminski, L. Nuñez and A. E. Visser, Sep. Sci. Technol., 1999,
34, 1103–1109.
12 M. Kaminski, S. Landsberger, L. Nuñez and G. F. Vandegrift, Sep. Sci.
Technol., 1997, 32, 115–126.
Extraction experiments
10 ml of the Eu/Am solution in 3 M HNO3 were added to 300 mg
magnetic particles. This suspension was shaken for one hour at
room temperature and afterwards separated with the help of a mag-
netic field. The activity of the radionuclide in the starting solution
and in the supernatant after shaking was determined by -spectrom-
etry. In a typical experiment the initial activity of 241Am (1381 kBq
l−1) and 152Eu (1511 kBq l−1) was reduced to 134 kBq l−1 and 309 kBq
l−1 respectively, by shaking with 300 mg of 2b, leading to KD values
of 310 ml g−1 and 130 ml g−1, respectively.
These conditions, leading to a low final activity of 10% or less
for particles 1–3, were chosen to study particles with the model
compounds 4a,b, where the final activity is 90% or more, under
identical conditions.
13 S. E. Matthews, P. Parzuchowski, A. Garcia Carrera, C. Grüttner, J.-F.
Dozol and V. Böhmer, Chem. Commun., 2001, 417–418.
14 Product information: www.micromod.de; product-code: 58-39-105.
15 To prepare tetraether 6a tert-butylcalix[4]arene was first alkylated
with bromopropylphthalimide (68%), followed by alkylation with
propylbromide (82%), see ref. 13.
Acknowledgements
This work was financially supported by the European Commission
in the framework of the research program “Selective extraction
of minor actinides from high activity liquid waste by organized
matrices”, CONTRACT No FIKW-CT2000-00088.
16 K. Winnacker and L. Küchler, Chemische Technologie, vol. 7(3), Carl
Hanser Verlag, München, 1975, p. 93–94.
17 K. A. Martin, E. P. Horwitz and J. R. Ferraro, Solv. Extr. Ion Exch.,
1986, 4, 1149–1169.
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2 3 3 4
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 2 7 – 2 3 3 4