Guest exchange in dimeric capsules formed by tetra-urea calix[4]arenes

Article abstract of DOI:10.1039/b719053k

Ten tetra-urea calix[4]arene derivatives with different ether residues (methyl, pentyl, benzyl, all combinations of methyl and pentyl, 1,3-dibenzyl-2,4-dipentyl), including also the tetrahydroxy compound and the 1,3-dipentyl ether, were synthesised. Their

Full text of DOI:10.1039/b719053k

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Guest exchange in dimeric capsules formed by tetra-urea calix[4]arenes†
Ivan Vatsouro, Ellen Alt, Myroslav Vysotsky and Volker Bo¨hmer*
Received 11th December 2007, Accepted 16th January 2008
First published as an Advance Article on the web 14th February 2008
DOI: 10.1039/b719053k
Ten tetra-urea calix[4]arene derivatives with different ether residues (methyl, pentyl, benzyl, all
combinations of methyl and pentyl, 1,3-dibenzyl-2,4-dipentyl), including also the tetrahydroxy
compound and the 1,3-dipentyl ether, were synthesised. Their urea groups were substituted with a
lipophilic residue to ensure sufficient solubility in cyclohexane. Thus, kinetics for the exchange of the
included guest (benzene) against the solvent (cyclohexane) could be followed by 1H NMR spectroscopy.
The apparent first order rate constants decrease with increasing size of the ether residues from methyl
to benzyl by more than three orders of magnitude. This can be understood by a decreasing
flexibility/mobility of the calixarene skeleton. In line with this explanation is the rather slow exchange
for the tetrahydroxy compound, where the cone conformation is stabilised by a cyclic array of
intramolecular OH · · · OH hydrogen bonds.
The guest included in a capsule can be exchanged with another
Introduction
guest and the mechanism of this guest exchange 1·G1·1 → 1·G2·1
The inclusion of guest molecules into the cavity of self-assembled
is another challenging problem. A simple opening of a single flap
as described for glycoluril based dimeric capsules10 is surely not
possible here. However, it seems at least possible that the hydrogen
bonded belt is partly retained. Yet, early studies by a series of 2D
NMR experiments suggested that the guest (benzene) included in
a dimeric capsule is exchanged with the solvent (benzene) via a
dissociation–recombination process.11 Much deeper insight into
the association and dissociation process was obtained by FRET
techniques, using tetra-urea derivatives marked by covalently
attached donor and acceptor dyes.12 The rate for the guest
release is lower if benzene is replaced by cyclohexane as solvent,
allowing kinetic measurements for the decyl ether of the tetratolyl
urea 1 (Y = C10H21, R = p-CH3–C6H4) and various guests by
“conventional” NMR spectroscopy.13 To elucidate the influence of
the ether residues on the kinetic stability, we have now conducted a
detailed kinetic study of the exchange of included benzene against
cyclohexane used as solvent.
capsules is a topic of steadily growing interest, since the first
example of a hydrogen bonded capsule was reported nearly
15 years ago.1 Calix[4]arenes substituted at their wide rim by four
urea functions (1) form dimeric capsules held together by a seam
of intermolecular hydrogen bonds between the urea groups.2,3
3
˚
The internal volume of about 190–200 A is large enough to
host suitably sized (neutral or cationic) guests. Although larger
capsules are known, including examples composed of more than
two molecular building blocks,4–6 dimers formed by 1 are attractive
and challenging due to their special geometry. The two calixarene
molecules are turned by 45◦ around their common axis and the
interdigitating urea groups of the two calixarenes point in opposite
directions including angles of 25–30◦ with the S4 axis of the
dimer and of 120–130◦ between adjacent urea groups. Functional
groups R attached to the urea residues are thus brought into
a unique mutual position.7,8 This has been used, for instance,
to synthesise various topologically interesting molecules, such as
multiple catenanes or rotaxanes.9
Results and discussion
To ensure sufficient solubility for all combinations of ether residues
we have chosen tetra-urea compounds 8 substituted by branched
tetradecyloxy phenyl groups. As ether groups, Y, we considered
initially methyl (small enough to pass the annulus) and pentyl
in all possible combinations. The series was later completed by
selected compounds with benzyl ether groups and free phenolic
hydroxy groups. Again, all exchange reactions could be monitored
by recording the NMR spectra as a function of time.
Syntheses
Fachbereich Chemie, Pharmazie und Geowissenschaften, Johannes
Gutenberg-Universita¨t Mainz, Duesbergweg 10-14, D-55099, Mainz, Ger-
many. E-mail: vboehmer@mail.uni-mainz.de; Fax: +49 (0)6131 3925419;
Tel: +49 (0)6131 3922319
The main synthetic steps are summarised in Scheme 1.
All tetra-urea derivatives were obtained by acylation of the
respective tetraamino calix[4]arene 4 with the isocyanate obtained
in situ from the alkoxy aniline 7 with triphosgene. 7 was prepared
by O-alkylation of N-(p-hydroxyphenyl)acetamide 5, followed
by alkaline hydrolysis. Tetraamino calix[4]arenes 4 were usually
† Electronic supplementary information (ESI) available: Experimental
1
details for the preparation of new compounds 2–7; H NMR spectra of
tetra-ureas 8 in cyclohexane-d12; rate constants for separate kinetic runs.
See DOI: 10.1039/b719053k
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Scheme 1 Synthesis of tetra-urea derivatives, 8, used for the kinetic studies. Ether residues Y are indicated by letters M (= methyl), P (= pentyl), B (=
benzyl) and H (free OH group) as subscript, e.g. 8MPPP = methyltripentyl ether, 8BBBB = tetrabenzyl ether, 8PHPH = 1,3-dipentyl ether.
synthesised by ipso-nitration (60–77%) of the corresponding
tetraethers 2 of tert-butylcalix[4]arene and subsequent hydrogena-
tion. Mixed pentyl/methyl ethers of tert-butylcalixarene were
prepared via the mono-, di- and tripentyl ethers followed by
exhaustive O-methylation.14 This sequence is essential to ensure
that all pentyl ether groups are in a syn-orientation.
Since all attempts to ipso-nitrate the tetrabenzyl ether of tert-
butylcalix[4]arene (2BBBB) failed, the respective tetraamine 4BBBB
was prepared as described.2 The tetraamine 4PBPB was synthesised
analogously. The dibenzyldipentyl ether of p-H-calix[4]arene,
obtained by 1,3-dibenzylation followed by exhaustive O-alkylation
with pentylbromide, was iodinated, substituted by phthalimide
and finally reacted with hydrazine.
compound (such as benzene) are much less reliably monitored,
than those of non-volatile compounds. (For details see the
experimental part).
As anticipated, clean first order reactions were observed for
all compounds from 5% up to conversions of 70–80%. Plots are
shown in Fig. 2, which show linearity during the course of the
exchange reaction with the exception of the initial period of the
reaction. Presently it is not clear if the slight but distinct deviations
observed in the very beginning are due to an artefact. Fig. 2
contains plots for three examples from which the apparent first
order rate constants are easily derived as the slopes of their linear
parts. These values are collected in Table 1. Since they differ by a
factor higher than 103 the respective half-life times are visualised
in Fig. 3 using a logarithmic scale.
It can be easily shown, that the rate of the guest exchange
increases upon addition of small amounts of water. Although the
measurements were done under dry conditions (see experimental
part), the available technique did not allow us to exclude traces
of water completely. This may be the reason why a reproducibility
of 10% was observed for the rate constants within a period of
The whole synthetic sequence was followed step-by-step by 1H
NMR spectroscopy, which in this case is the most appropriate
analytical technique. Only partially methylated nitro- and amino-
compounds could not be easily characterised due to their confor-
mational flexibility. However, the dimeric capsule of the tetra-urea
1
derivative showed a well resolved H NMR spectrum. On the
other hand, for tetra-urea derivatives with Cs-symmetry (8MMMP
,
8
MMPP, 8MPPP) two regioisomeric capsules exist, which leads to
rather complicated spectra.15 Nevertheless, they could be analysed,
showing that both capsules were formed with the same probability.
(Kinetic data refer to this average).
Kinetics
The 1H NMR spectra of the dimeric capsules containing benzene
or cyclohexane-d12 are sufficiently different so as to enable a rapid
identification as to the identity of the encapsulated guest. Thus,
the exchange could be followed by NMR spectroscopy, using the
more or less resolved signal(s) of the benzene-filled capsules (in
most cases a urea NH signal). An example is shown in Fig. 1.
Intuitively it might be more reasonable to use the increasing
signal of free benzene in cyclohexane. However, due to the long
reaction times (often several weeks), the signals of a volatile
Fig. 1 Section of the NMR spectrum of 8PPPP as a function of time,
illustrating the exchange of encapsulated benzene by cyclohexane-d12; red:
signals for free (eꢀ) and included (e) benzene, green: signals for the new
complex (aꢀ–dꢀ), the respective signals of the initial complex are marked as
a–d.
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Table 1 Apparent first order rate constants for the exchange of benzene
by cyclohexane-d12
Tentatively this may be explained by an increasing rigidity
(decreasing flexibility) of the calixarene skeleton with increasing
size of the ether groups. A tetraether with ether residues equal to
or larger than propyl is kept in one of the basic conformations,
e.g. the cone conformation, which however is “pinched” due to the
repulsion of the ether residues. Methoxy groups still can pass the
annulus of the calix[4]arene and for the same reason a tetramethyl
ether normally prefers the partial cone conformation.16 Within
the dimeric capsule the calixarenes are kept in a regular (C4-
symmetrical) cone conformation. The opening of the capsule by
bending one (or several) urea residues outwards, means that the
corresponding ether residues must be bent inwards. And this is
obviously more easily facilitated for small ether residues where the
repulsion is lower.
Tetra-urea
k/h−1
8MMMM
8MMMP
8MPMP
8MMPP
8MPPP
8PPPP
0.47 0.03
0.37 0.02
0.35 0.02
0.090 0.008
0.052 0.003
0.027 0.003
0.0082 0.0001
0.00026 0.00007
0.031 0.002
0.0039 0.0003
8PBPB
8BBBB
8PHPH
8HHHH
This explanation is further corroborated by the whole series of
compounds with methyl and pentyl ether groups 8MMMM to 8PPPP
,
which show decreasing rate constants with increasing number of
pentyl ether groups. Interestingly, the alternating arrangement in
8MPMP leads to 3.9 times higher rates for the guest release than
the adjacent position of identical ether groups Y in 8MMPP. In this
alternating arrangement the inwards moving methyl group faces
the opposite methyl group. An opposite pentyl ether group as in
8MMPP might cause a stronger repulsion, which explains the lower
exchange rate.
A slow exchange reaction is also observed for 8HHHH and may be
explained in a similar way, although in this case the main reason
for the stabilisation of the cone conformation is the cyclic belt of
intramolecular OH · · · OH hydrogen bonds between the phenolic
hydroxyl groups. A lower stability for the capsule of 8PHPH is in
line with this but a further interpretation in comparison with the
tetraether derivatives is not possible on the basis of the present
results.
Fig. 2 Examples of first order plots for the exchange of encapsulated
benzene by cyclohexane-d12.
Conclusions
We have shown that the rate of guest exchange strongly depends
on the size of the ether groups attached to the narrow rim of tetra-
urea calix[4]arenes. This is in keeping with a mechanism where the
opening of the capsule is connected with an outwards movement
of the urea residues, necessarily accompanied by an inward motion
of the alkoxy groups. This movement is sterically hindered by the
repulsion of the ether residues, which increases with increasing
size. Although other mechanisms for the guest exchange might be
also possible, e.g. an opening by rotation around the aryl–urea–
aryl axis, the proposed explanation is in agreement with the lower
rate of guest exchange found for capsules where the calix[4]arenes
are rigidified by two short crown ether groups.17
Fig. 3 Illustration of the half-life times for the exchange of encapsulated
benzene by cyclohexane-d12 for the series of compounds 8.
Experimental
1–2 months (using also the same samples of cyclohexane-d12 and
benzene) while the reproducibility is lower over a longer period.
However, for the present discussion it is only important that the
apparent rate constants can be compared within the set of data
presented in Table 1.
Among the tetraether derivatives with identical ether residues
Y (8MMMM, 8PPPP and 8BBBB) the rate of the guest release decreases
drastically with increasing size of Y. The ratio of the rate constants
for capsules formed by 8MMMM, 8PPPP and 8BBBB is 1808 : 104 : 1.
Mixed tetraethers show intermediate rates.
Cyclohexane-d12 (Deutero GmbH, 99.5 atom% D) and benzene
(Riedel-de Hae¨n, p.a.) were treated as described below. All other
solvents and commercially available chemicals were purchased
from Acros and Aldrich, and used without further purification.
NMR spectra were recorded on a Bruker Avance DRX400
spectrometer at 25 ◦C if not stated otherwise. FD- and ESI-mass
spectra were measured on Finnigan MAT 8230 and Micromass
QToF Ultima 3 instruments. Melting points were determined
with a MEL TEMP 2 capillary melting point apparatus and
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14
are uncorrected. 1-Bromo-2-hexyloctane,18 tetraamines 4MMMM
,
7.03 (d, J 9.2 Hz, 4H, ArHPh), 6.95 (d, J 8.9 Hz, 4H, ArHPh),
6.92 (d, J 8.9 Hz, 4H, ArHPh), 6.82 (d, J 9.2 Hz, 4H, ArHPh), 6.54
(d, J 2.2 Hz, 2H, ArH), 6.47 (d, J 2.2 Hz, 2H, ArH), 6.40 (d, J
2.2 Hz, 2H, ArH), 6.38 (d, J 2.2 Hz, 2H, ArH), 4.53 (d, J 12.1 Hz,
2H, ArCH2Ar), 4.47 (d, J 12.1 Hz, 2H, ArCH2Ar), 4.44 (d, J
12.1 Hz, 2H, ArCH2Ar), 4.41 (d, J 12.1 Hz, 2H, ArCH2Ar), 3.92
(s, 12H, OCH3), 3.71–3.47 (m, 24H, OCH2), 3.43 (d, J 12.1 Hz,
2H, ArCH2Ar), 3.31 (d, J 12.1 Hz, 2H, ArCH2Ar), 3.29 (d, J
12.1 Hz, 2H, ArCH2Ar), 3.20 (d, J 12.1 Hz, 2H, ArCH2Ar), 1.97
(m, 8H, CH2), 1.74 (m, 8H, CH), 1.57–1.16 (m, 176H, CH2) and
1.09–0.90 (m, 60H, CH3). Monomer: dH(400 MHz; DMSO-d6–
CDCl3) 8.31 (s, 2H, NH), 8.22 (s, 2H, NH), 7.88 (s, 2H, NH),
7.78 (s, 2H, NH), 7.31 (d, J 8.9 Hz, 4H, ArHPh), 7.21 (s, 4H,
ArH), 7.09 (d, J 8.9 Hz, 4H, ArHPh), 6.77 (d, J 8.9 Hz, 4H,
ArHPh), 6.68 (d, J 8.9 Hz, 4H, ArHPh), 6.48 (s, 4H, ArH), 4.26
(d, J 11.4 Hz, 4H, ArCH2Ar), 3.88 (s, 6H, OCH3), 3.75 (d, J
5.4 Hz, 4H, OCH2CH), 3.70 (d, J 5.4 Hz, 4H, OCH2CH), 3.63
(br s, 4H, OCH2), 3.09 (d, J 11.4 Hz, 4H, ArCH2Ar), 1.87 (m,
4H, CH2), 1.68 (m, 4H, CH), 1.55 (m, 4H, CH2), 1.47–1.11 (m,
84H, CH2), 0.92 (t, J 7.3 Hz, 6H, CH3) and 0.88–0.76 (m, 24H,
19
11
2
4PPPP
,
4MPMP and 4BBBB
,
and p-H-calix[4]arene 1,3-dibenzyl
ether20 were described previously. Synthesis and characterisation
of the new compounds 2–7 are reported in the ESI.†
Synthesis
General procedure for the preparation of tetra-urea calixarenes 8
from tetraamines 4. Triphosgene (0.36 g, 1.2 mmol) was added
to a stirred solution of 4-[(2-hexyloctyl)oxy]aniline 7 (0.37 g,
1.2 mmol) in toluene (70 ml). The solution was refluxed under
nitrogen for 1 h, cooled and the solvent evaporated in vacuo at
70–80 ◦C. The resultant oil was dissolved in toluene (5 ml) and
the solution of the respective calixarene 4 (0.2 mmol) in toluene
(30 ml) was added. The reaction mixture was stirred overnight at
room temperature and then concentrated in vacuo. The residue
was finally purified by column chromatography (gradient from
dichloromethane to dichloromethane–ethanol, 30 : 1).
Calix[4]arene 8MMMM
.
Yield 62%, mp 192–194 ◦C. Dimer:
dH(400 MHz; C6D6) 9.68 (s, 8H, NH), 8.07 (d, J 9.2 Hz, 16H,
ArHPh), 8.02 (d, J 2.2 Hz, 8H, ArH), 7.47 (s, 8H, NH), 6.87 (d,
J 9.2 Hz, 16H, ArHPh), 6.30 (d, J 2.2 Hz, 8H, ArH), 4.27 (d,
J 11.8 Hz, 8H, ArCH2Ar), 3.61 (s, 24H, OCH3), 3.57 (m, 16H,
OCH2CH), 3.17 (d, J 11.8 Hz, 8H, ArCH2Ar), 1.69 (m, 8H, CH),
1.51–1.15 (m, 160H, CH2), 0.91 (t, J 7.0 Hz, 24H. CH3) and 0.90 (t,
J 7.0 Hz, 24H, CH3). Monomer: dH(400 MHz; THF-d8) 7.57 (br s,
4H, NH), 7.40 (br s, 4H, NH), 7.26 (d, J 8.6 Hz, 8H, ArHPh), 6.87
(s, 8H, ArH), 6.73 (d, J 8.6 Hz, 8H, ArHPh), 4.32 (d, J 12.7 Hz, 4H,
ArCH2Ar), 3.77 (br s, 20H, OCH3 + OCH2), 3.09 (d, J 12.7 Hz,
4H, ArCH2Ar), 1.57–1.21 (m, 84H, CH2), 0.89 (m, 24H. CH3) and
=
CH3). dC(100 MHz; DMSO-d6–CDCl3) 154.03, 153.87 (C O),
152.96, 152.78, 152.44, 150.72, 136.08, 134.25, 132.86, 132.67,
132.56, 132.45 (CAr), 119.70, 119.49, 118.49, 117.39, 114.31, 114.19
(CHAr), 75.07 (OCH2), 70.53 (OCH2CH), 60.21 (OCH3), 37.30
(CH), 31.20, 31.18, 30.76, 30.73 (CH2), 29.70 (ArCH2Ar), 29.05,
29.02, 27.91, 26.15, 26.13, 22.04, 22.01 (CH2), 13.76, 13.74 and
13.72 (CH3). ESI-MS m/z 2001.45 (100%), 2000.46 (57), 2002.46
(57) [M + Na]+ for C124H184NaN8O12 (2000.39).
Calix[4]arene 8MMPP
.
Yield 47%, mp 198–200 ◦C.21
dH(400 MHz; THF-d8) 7.61 (br s, 4H, NH), 7.51 (br s, 4H,
NH), 7.25 (br d, 8H, ArHPh), 6.84 (br s, 8H, ArH), 6.72 (br
d, 8H, ArHPh), 4.34 (br s, 4H, ArCH2Ar), 3.75 (br d, 8H,
OCH2CH), 3.73 (br s, 4H, OCH2), 3.57 (s, 6H, OCH3), 3.04 (br
d, 4H, ArCH2Ar), 1.93 (br s, 4H, CH2), 1.73 (br s, 4H, CH),
1.53–1.20 (m, 88H, CH2), 0.95 (br s, 6H, CH3) and 0.88 (br s,
=
0.90 (t, J 7.0 Hz, 24H, CH3). dC(100 MHz; THF-d8) 154.01 (C O),
152.53, 151.97, 134.22, 133.80, 132.80 (CAr), 118.94, 117.74, 113.67
(CHAr), 70.11 (OCH2CH), 60.35 (OCH3), 37.63 (CH), 31.30, 30.84
(CH2), 30.12 br s (ArCH2Ar), 29.16, 26.26, 22.03 (CH2) and 12.92
(CH3). ESI-MS m/z 1889.26 (100%), 1888.26 (64), 1890.26 (46)
[M + Na]+ for C116H168NaN8O12 (1888.27).
=
24H, CH3). dC(100 MHz; THF-d8) 155.54 (C O), 153.85 br s,
.
Yield 62%, mp 190–192 ◦C.21
153.76, 152.83, 135.90 br s, 135.60 br s, 135.24 br s, 135.01 br s,
134.30 (CAr), 120.55, 119.63 br s, 115.20 (CHAr), 76.01 (OCH2),
71.66 (OCH2CH), 61.66 (OCH3), 39.16 (CH), 32.82, 32.37, 30.68
(CH2), 29.44 (ArCH2Ar), 27.79, 23.68, 23.55 (CH2), 14.60 and
14.45 (CH3). ESI-MS m/z 2001.44 (100%), 2000.44 (60), 2002.45
(60) [M + Na]+ for C124H184NaN8O12 (2000.39).
Calix[4]arene 8MMMP
dH(400 MHz; THF-d8; 0 ◦C) 8.00–7.47 (m, 6H, NH), 7.46–
7.07 (m, 14H, NH + ArHPh + ArH), 6.84–6.60 (m, 8H, ArHPh),
6.47 (br s, 4H, ArH), 4.31 (br d, 3H, ArCH2Ar), 4.03 (br s, 1H,
ArCH2Ar), 3.95–3.60 (m, 19H, OCH2 + OCH3 + OCH2CH),
3.09 (m, 4H, ArCH2Ar), 1.90 (m, 2H, CH2), 1.61 (m, 2H, CH),
1.53–1.16 (m, 86H, CH + CH2), 0.96 (t, J 7.1 Hz, 3H, CH3) and
Calix[4]arene 8MPPP
.
Yield 54%, mp 200–202 ◦C.21
=
0.88 (m, 24H, CH3). dC(100 MHz; THF-d8) 155.56, 155.52 (C O),
dH(400 MHz; THF-d8; 0 ◦C) 7.95 (s, 1H, NH), 7.94 (s, 1H,
NH), 7.80 (s, 2H, NH), 7.50 (s, 2H, NH), 7.44–7.19 (m, 10H, NH
+ ArHPh + ArH), 7.14 (br d, J 7.8 Hz, 4H, ArHPh), 6.77 (br d, J
7.8 Hz, 4H, ArHPh), 6.65 (br d, J 8.3 Hz, 4H, ArHPh), 6.40 (m,
4H, ArH), 4.42 (d, J 12.2 Hz, 2H, ArCH2Ar), 4.30 (d, J 12.2 Hz,
2H, ArCH2Ar), 4.06 (m, 2H, OCH2), 3.89–3.60 (m, 15H, OCH2
+ OCH3 + OCH2CH), 3.06 (d, J 12.2 Hz, 4H, ArCH2Ar), 2.07
(m, 2H, CH2), 1.89 (m, 4H, CH), 1.63–1.16 (m, 96H, CH2), 0.96
(t, J 7.1 Hz, 9H, CH3) and 0.87 (m, 24H, CH3). dC(100 MHz;
154.49, 153.68, 153.59, 152.48, 137.38, 137.32, 135.81, 134.78,
134.60, 134.43, 134.35, 134.20 (CAr), 120.55, 120.47, 119.42 br s,
115.23, 115.15 (CHAr), 75.93 (OCH2), 71.66 (OCH2CH), 62.55,
61.30 (OCH3), 39.16 (CH), 32.83, 32.39, 32.36, 31.80, 31.64,
31.18, 30.69 (CH2), 29.55 (ArCH2Ar), 27.79, 23.55 (CH2) and
14.45 (CH3). ESI-MS m/z 1945.37 (100%), 1944.37 (63), 1946.37
(58) [M + Na]+ for C120H176NaN8O12 (1944.33).
Calix[4]arene 8MPMP
.
Yield 43%, mp 193–195 ◦C. Dimer:
=
dH(400 MHz; C6D6) 9.90 (s, 2H, NH), 9.88 (s, 2H, NH), 9.81
(s, 2H, NH), 9.79 (s, 2H, NH), 8.46 (d, J 2.2 Hz, 2H, ArH), 8.27
(br s, 2H, ArH), 8.25 (d, J 8.9 Hz, 4H, ArHPh), 8.18 (d, J 8.9 Hz,
4H, ArHPh), 8.17 (d, J 9.2 Hz, 4H, ArHPh), 8.07 (br s, 2H, ArH),
8.05 (d, J 9.2 Hz, 4H, ArHPh), 7.78 (d, J 2.2 Hz, 2H, ArH), 7.70
(s, 2H, NH), 7.67 (s, 2H, NH), 7.35 (s, 2H, NH), 7.34 (s, 2H, NH),
THF-d8) 155.54, 155.52 (C O), 154.54, 153.91, 153.66, 153.58,
152.23, 137.51, 137.40, 135.71, 135.38, 134.58, 134.47, 134.44,
134.16, 134.09 (CAr), 120.59, 120.47, 120.44, 119.66, 119.57,
115.23, 115.14 (CHAr), 75.98 (OCH2), 71.66 (OCH2CH), 61.27
(OCH3), 39.18, 39.15 (CH), 32.83, 32.40, 32.35 (CH2), 31.97
(br s, ArCH2Ar), 31.16 (CH2), 30.69, 29.62 (CH2), 29.27 (br s,
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ArCH2Ar), 27.80, 23.80, 23.62, 23.56 (CH2), 14.52 and 14.46
(CH3). ESI-MS m/z 2057.44 (100%), 2058.45 (61), 2056.44 (57)
[M + Na]+ for C128H192NaN8O12 (2056.46).
ESI-MS m/z 2153.56 (100%), 2154.56 (46), 2152.56 (27) [M +
Na]+ for C136H192NaN8O12 (2152.46).
Calix[4]arene 8BBBB
.
Yield 75%, mp 182–184 ◦C. Dimer:
dH(400 MHz; C6D6) 9.77 (s, 8H, NH), 8.11 (d, J 2.2 Hz, 8H,
ArH), 8.02 (d, J 9.2 Hz, 16H, ArHPh), 7.49 (s, 8H, NH), 7.50 (br t,
J 7.2 Hz, 8H, ArHBz), 7.29 (br t, J 7.2 Hz, 16H, ArHBz), 7.21 (br
d, J 7.2 Hz, 16H, ArHBz), 6.82 (d, J 9.2 Hz, 16H, ArHPh), 6.33 (d,
J 2.2 Hz, 8H, ArH), 4.85 (d, J 12.1 Hz, 8H, OCH2Ph), 4.58 (d, J
12.1 Hz, 8H, OCH2Ph), 3.97 (d, J 12.1 Hz, 8H, ArCH2Ar), 3.60
(m, 16H, OCH2), 2.75 (d, J 12.1 Hz, 8H, ArCH2Ar), 1.72 (m, 8H,
CH), 1.45 (m, 16H, CH2), 1.39–1.14 (m, 144H, CH2) and 0.88 (t, J
6.5 Hz, 48H, CH3). Monomer: dH(400 MHz; THF-d8) 7.47 (s, 4H,
NH), 7.38–7.33 (m, 12H, NH + ArHBz), 7.27–7.19 (m, 20H, ArHPh
+ ArHBz), 6.76 (s, 8H, ArH), 6.73 (d, J 9.2 Hz, 8H, ArHPh), 4.94
(s, 8H, OCH2Ph), 4.21 (d, J 13.3 Hz, 4H, ArCH2Ar), 3.78 (d, J
5.5 Hz, 8H, OCH2CH), 2.84 (d, J 13.3 Hz, 4H, ArCH2Ar), 1.53–
1.24 (m, 84H, CH + CH2) and 0.89 (m, 24H, CH3). dC(100 MHz;
Calix[4]arene 8PPPP
.
Yield 71%, mp 202–204 ◦C. Dimer:
dH(400 MHz; C6D6) 9.92 (s, 8H, NH), 8.15 (d, J 2.2 Hz, 8H,
ArH), 8.13 (d, J 9.2 Hz, 16H, ArHPh), 7.41 (s, 8H, NH), 6.85 (d,
J 9.2 Hz, 16H, ArHPh), 6.49 (d, J 2.2 Hz, 8H, ArH), 4.61 (d, J
11.8 Hz, 8H, ArCH2Ar), 3.76 (m, 16H, OCH2), 3.53 (d, J 5.7 Hz,
16H, OCH2CH), 3.33 (d, J 11.8 Hz, 8H, ArCH2Ar), 2.12 (m,
16H, CH2), 1.68 (m, 8H, CH), 1.52–1.16 (m, 192H, CH2), 1.02 (t,
J 7.3 Hz, 24H, CH3), 0.91 (t, J 6.8 Hz, 24H, CH3) and 0.90 (t,
J 6.8 Hz, 24H, CH3). Monomer: dH(400 MHz; THF-d8) 7.51 (s,
4H, NH), 7.39 (s, 4H, NH), 7.25 (d, J 8.6 Hz, 8H, ArHPh), 6.81 (s,
8H, ArH), 6.72 (d, J 8.6 Hz, 8H, ArHPh), 4.44 (d, J 13.0 Hz, 4H,
ArCH2Ar), 3.87 (t, J 6.7 Hz, 8H, OCH2), 3.78 (d, J 5.1 Hz, 8H,
OCH2CH), 3.07 (d, J 13.0 Hz, 4H, ArCH2Ar), 1.95 (m, 8H, CH2),
1.56–1.16 (m, 100H, CH + CH2), 0.98 (t, J 6.7 Hz, 12H, CH3) and
=
THF-d8) 153.96 (C O), 151.89, 149.87, 137.57, 134.67, 133.79,
=
0.89 (m, 24H, CH3). dC(100 MHz; THF-d8) 153.96 (C O), 151.96,
132.85 (CAr), 129.14, 127.17, 126.87, 118.86, 117.68, 113.63 (CHAr),
75.73 (OCH2), 70.10 (OCH2CH), 37.63 (CH), 31.30 (CH2), 31.06
(ArCH2Ar), 30.84, 29.15, 26.26, 22.02 (CH2) and 12.92 (CH3).
ESI-MS m/z 1108.23 (100%), 1108.73 (63), 1107.72 (34) [M +
2Na]2+ for C140H184Na2N8O12 (2215.38) and 2193.45 (28), 2194.42
(20) [M + Na]+ for C140H184NaN8O12 (2192.39).
151.07, 134.34, 133.54, 132.86 (CAr), 118.86, 117.81, 113.63 (CHAr),
74.31 (OCH2), 70.11 (OCH2CH), 37.64 (CH), 31.29, 30.84 (CH2),
30.62 (ArCH2Ar), 29.36, 29.16, 27.98, 26.26, 22.25, 22.02 (CH2),
13.09 and 12.92 (CH3). ESI-MS m/z 2113.52 (100%), 2114.52 (69),
2112.52 (53) [M + Na]+ for C132H200NaN8O12 (2112.52).
Calix[4]arene 8PHPH
. Pd/C (10%, 0.048 g, 0.045 mmol) was
Calix[4]arene 8PBPB
.
Yield 89%, mp 198–200 ◦C. Dimer:
added to a solution of 8PBPB (0.096 g, 0.045 mmol) in THF (30 ml)
and the mixture was stirred at room temperature under H2 for 14 h.
The reaction mixture was filtered and the filtrate concentrated. The
product was re-precipitated f◦rom dichloromethane–ethanol. Yield
51% (0.045 g), mp 220–222 C. Dimer: dH(400 MHz; C6D6) 9.67
(s, 2H, NH), 9.66 (s, 2H, NH), 9.40 (s, 2H, NH), 9.38 (s, 2H, NH),
8.50 (s, 2H, OH), 8.49 (s, 2H, OH), 8.30 (d, J 2.2 Hz, 2H, ArH),
8.19 (d, J 2.2 Hz, 2H, ArH), 8.13 (br s, 2H, ArH), 8.11 (d, J 8.9 Hz,
4H, ArHPh), 8.07 (d, J 8.9 Hz, 4H, ArHPh), 8.03 (d, J 8.9 Hz, 4H,
ArHPh), 7.99 (d, J 8.9 Hz, 4H, ArHPh), 7.98 (br s, 2H, ArH), 7.84
(s, 2H, NH), 7.81 (s, 2H, NH), 7.76 (s, 2H, NH), 7.71 (s, 2H, NH),
6.95 (d, J 8.9 Hz, 4H, ArHPh), 6.89 (d, J 8.9 Hz, 4H, ArHPh),
6.87 (d, J 8.9 Hz, 4H, ArHPh), 6.82 (d, J 8.9 Hz, 4H, ArHPh), 6.39
(d, J 2.2 Hz, 2H, ArH), 6.35 (d, J 2.2 Hz, 2H, ArH), 6.34 (d, J
2.2 Hz, 2H, ArH), 6.33 (d, J 2.2 Hz, 2H, ArH), 4.42 (d, J 12.6 Hz,
2H, ArCH2Ar), 4.39 (d, J 12.6 Hz, 2H, ArCH2Ar), 4.32 (d, J
12.6 Hz, 2H, ArCH2Ar), 4.28 (d, J 12.6 Hz, 2H, ArCH2Ar), 3.68–
3.42 (m, 24H, OCH2), 3.35 (d, J 12.6 Hz, 2H, ArCH2Ar), 3.32
(d, J 12.6 Hz, 2H, ArCH2Ar), 3.25 (d, J 12.6 Hz, 2H, ArCH2Ar),
3.22 (d, J 12.6 Hz, 2H, ArCH2Ar), 2.03 (m, 8H, CH2), 1.71 (m,
4H, CH), 1.63 (m, 4H, CH), 1.55–1.09 (m, 176H, CH2), 1.04 (t,
J 7.0 Hz, 6H, CH3), 1.03 (t, J 6.8 Hz, 6H, CH3) and 0.90 (m,
48H, CH3). Monomer: dH(400 MHz; DMSO-d6–CDCl3) 8.13 (s,
2H, NH), 8.08 (s, 2H, OH), 8.07 (s, 2H, NH), 8.06 (s, 2H, NH),
8.03 (s, 2H, NH), 7.25 (d, J 9.2 Hz, 4H, ArHPh), 7.16 (d, J 9.2 Hz,
4H, ArHPh), 7.12 (s, 4H, ArH), 7.02 (s, 4H, ArH), 6.72 (d, J 9.2 Hz,
4H, ArHPh), 6.69 (d, J 9.2 Hz, 4H, ArHPh), 4.19 (d, J 12.7 Hz, 4H,
ArCH2Ar), 3.91 (br t, J 6.5 Hz, 4H, OCH2), 3.71 (d, J 5.7 Hz, 4H,
OCH2CH), 3.69 (d, J 5.7 Hz, 4H, OCH2CH), 3.28 (d, J 12.7 Hz,
4H, ArCH2Ar), 2.00 (m, 4H, CH2), 1.67 (m, 8H, CH + CH2), 1.47
(m, 4H, CH2), 1.40–1.12 (m, 80H, CH2), 0.97 (t, J 7.3 Hz, 6H,
CH3), 0.82 (t, J 6.8 Hz, 12H, CH3) and 0.82 (t, J 6.5 Hz, 12H, CH3).
dH(400 MHz; C6D6) 9.95 (s, 4H, NH), 9.90 (s, 2H, NH), 9.89
(s, 2H, NH), 8.26 (d, J 2.2 Hz, 2H, ArH), 8.21 (d, J 2.2 Hz, 2H,
ArH), 8.18 (d, J 8.9 Hz, 4H, ArHPh), 8.17 (br d, 4H, ArH), 8.15
(d, J 8.9 Hz, 4H, ArHPh), 8.14 (d, J 8.9 Hz, 4H, ArHPh), 8.11
(d, J 8.9 Hz, 4H, ArHPh), 7.57 (s, 2H, NH), 7.54–7.45 (m, 12H,
NH + ArHBz), 7.40 (s, 2H, NH), 7.39–7.33 (m, 12H, ArHBz), 6.92
(d, J 8.9 Hz, 4H, ArHPh), 6.89 (d, J 8.9 Hz, 4H, ArHPh), 6.88
(d, J 8.9 Hz, 4H, ArHPh), 6.87 (d, J 8.9 Hz, 4H, ArHPh), 6.53
(d, J 2.2 Hz, 4H, ArH), 6.47 (d, J 2.2 Hz, 2H, ArH), 6.45 (d, J
2.2 Hz, 2H, ArH), 4.70 (d, J 12.0 Hz, 2H, OCH2Ph), 4.88 (d, J
12.0 Hz, 2H, OCH2Ph), 4.77 (d, J 12.0 Hz, 2H, OCH2Ph), 4.76 (d, J
12.0 Hz, 2H, OCH2Ph), 4.54 (d, J 12.0 Hz, 2H, ArCH2Ar), 4.53 (d,
J 12.0 Hz, 2H, ArCH2Ar), 4.40 (d, J 12.0 Hz, 2H, ArCH2Ar), 4.38
(d, J 12.0 Hz, 2H, ArCH2Ar), 3.72–3.50 (m, 24H, OCH2), 3.27 (d,
J 12.0 Hz, 2H, ArCH2Ar), 3.23 (d, J 12.0 Hz, 2H, ArCH2Ar), 3.11
(d, J 12.0 Hz, 2H, ArCH2Ar), 3.06 (d, J 12.0 Hz, 2H, ArCH2Ar),
1.76 (m, 16H, CH + CH2), 1.55–1.15 (m, 176H, CH2), 1.10 (m,
12H, CH3) and 1.00–0.89 (m, 48H, CH3). Monomer: dH(400 MHz;
THF-d8) 7.66 (s, 2H, NH), 7.54 (s, 2H, NH), 7.50 (m, 4H, ArHBz),
7.41 (s, 2H, NH), 7.36–7.27 (m, 10H, ArHPh + ArHBz), 7.25 (s, 2H,
NH), 7.17 (d, J 8.9 Hz, 4H, ArHPh), 7.07 (s, 4H, ArH), 6.76 (d,
J 8.9 Hz, 4H, ArHPh), 6.68 (d, J 8.9 Hz, 4H, ArHPh), 6.56 (s, 4H,
ArH), 4.80 (s, 4H, OCH2Ph), 4.41 (d, J 13.2 Hz, 4H, ArCH2Ar),
3.84 (m, 4H, OCH2), 3.79 (d, J 5.9 Hz, 4H, OCH2CH), 3.75 (d,
J 5.9 Hz, 4H, OCH2CH), 3.02 (d, J 13.2 Hz, 4H, ArCH2Ar),
1.53–1.00 (m, 96H, CH + CH2) and 0.92–0.82 (m, 30H, CH3).
=
dC(100 MHz; THF-d8) 155.55, 155.47 (C O), 153.66, 153.61,
153.13, 151.33, 139.20, 136.87, 135.16, 135.12, 134.40, 134.29
(CAr), 130.03, 128.86, 128.47, 120.47, 120.43, 119.51, 119.43,
115.22, 115.14 (CHAr), 77.85, 75.81 (OCH2), 71.65 (OCH2CH),
39.16 (CH), 32.82, 32.38, 32.36, 32.27, 30.67, 30.30 (CH2), 29.06
(ArCH2Ar), 27.79, 23.55, 23.52 (CH2), 14.73 and 14.45 (CH3).
=
dC(100 MHz; DMSO-d6–CDCl3) 154.03, 153.97 (C O), 152.85,
1002 | Org. Biomol. Chem., 2008, 6, 998–1003
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152.53, 147.85, 147.46, 136.16, 133.49, 132.54, 130.98, 127.65,
126.32 (CAr), 119.74, 119.68, 119.38, 118.47, 114.23, 114.17 (CHAr),
76.34 (OCH2), 70.54 (OCH2CH), 37.29, 37.27 (CH), 31.18, 30.73,
30.71, 29.02, 29.01, 28.06, 27.49, 26.14, 26.12, 22.02, 21.92 (CH2),
13.76 and 13.72 (CH3). ESI-MS m/z 1973.44 (100%), 1972.44 (50),
1974.44 (41) [M + Na]+ for C122H180NaN8O12 (1972.36).
runs were performed. Measurements at different concentrations
(1.0 mM to 4.0 mM) did not show any significant deviation or
trend in the rate constants, thus confirming the first order rate law.
The individual exchange rate values for each run are given in the
ESI.†
Calix[4]arene 8HHHH was obtained from calixarene 8BBBB (0.271 g,
0.125 mmol) and Pd/C (10%, 0.133 g, 0.125 mmol) in THF
(40 ml) as described for 8PHPH. Yield 95% (0.22 g), mp 244–246 ◦C
(decomp.). Dimer: dH(400 MHz; C6D6) 10.13 (s, 8H, OH), 9.19
(s, 8H, NH), 8.01 (d, J 2.2 Hz, 8H, ArH), 7.93 (d, J 8.9 Hz,
16H, ArHPh), 7.87 (s, 8H, NH), 6.90 (d, J 8.9 Hz, 16H, ArHPh),
6.11 (d, J 2.2 Hz, 8H, ArH), 4.00 (d, J 13.4 Hz, 8H, ArCH2Ar),
3.62 (m, 16H, OCH2), 3.18 (d, J 13.4 Hz, 8H, ArCH2Ar), 1.71
(m, 8H, CH), 1.43 (m, 16H, CH2), 1.37–1.16 (m, 144H, CH2)
and 0.90 (m, 48H, CH3). Monomer: dH(400 MHz; DMSO-d6–
CDCl3) 9.66 (s, 4H, OH), 8.08 (s, 4H, NH), 7.96 (s, 4H, NH),
7.16 (d, J 8.9, 8H, ArHPh), 7.10 (s, 8H, ArH), 6.67 (d, J 8.9 Hz,
8H, ArHPh), 4.14 (br s, 4H, ArCH2Ar), 3.67 (br d, J 5.1 Hz,
8H, OCH2CH), 3.37 (br s, 4H, ArCH2Ar), 1.63 (m, 4H, CH),
1.41–1.05 (m, 80H, CH2) and 0.79 (m, 24H, CH3). dC(100 MHz;
Acknowledgements
Financial support from the Deutsche Forschungsgemeinschaft
(Bo 523/14, SFB 625) and from the European Community (project
EUROPART) is gratefully acknowledged.
References
1 R. Wyler, J. de Mendoza and J. Rebek, Jr., Angew. Chem., Int. Ed. Engl.,
1993, 32, 1699–1701.
2 K. D. Shimizu and J. Rebek, Jr., Proc. Natl. Acad. Sci. U. S. A., 1995,
92, 12403–12407.
3 B. C. Hamann, K. D. Shimizu and J. Rebek, Jr., Angew. Chem., Int. Ed.
Engl., 1996, 35, 1326–1329.
4 J. M. C. A. Kerckhoffs, F. W. B. van Leeuwen, A. L. Spek, H. Kooijman,
M. Crego-Calama and D. N. Reinhoudt, Angew. Chem., Int. Ed., 2003,
42, 5717–5722.
5 T. Evan-Salem, I. Baruch, L. Avram, Y. Cohen, L. C. Palmer and J.
Rebek, Jr., Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 12296–12300.
6 L. R. MacGillivray and J. L. Atwood, Nature, 1997, 389, 469–472.
7 O. Mogck, E. F. Paulus, V. Bo¨hmer, I. Thondorf and W. Vogt, Chem.
Commun., 1996, 2533–2534.
8 I. Thondorf, F. Broda, K. Rissanen, M. Vysotsky and V. Bo¨hmer,
J. Chem. Soc., Perkin Trans. 2, 2002, 1796–1800.
=
DMSO-d6–CDCl3) 154.15 (C O), 152.74, 143.33, 133.38, 132.16,
128.18 (CAr), 119.83, 118.38, 114.17 (CHAr), 70.60 (OCH2CH),
37.30 (CH), 31.18, 30.72, 29.02, 26.14, 22.01 (CH2) and 11.66
(CH3). ESI-MS m/z 1833.23 (100%), 1832.23 (56), 1834.23 (28)
[M + Na]+ for C112H160NaN8O12 (1832.21).
9 A. Bogdan, Y. Rudzevich, M. O. Vysotsky and V. Bo¨hmer, Chem.
Commun., 2006, 2941–2952.
10 J. M. Rivera, S. L. Craig, T. Martin and J. Rebek, Jr., Angew. Chem.,
Int. Ed., 2000, 39, 2130–2132.
11 O. Mogck, M. Pons, V. Bo¨hmer and W. Vogt, J. Am. Chem. Soc., 1997,
119, 5706–5712.
12 R. K. Castellano, S. L. Craig, C. Nuckolls and J. Rebek, Jr., J. Am.
Chem. Soc., 2000, 122, 7876–7882.
13 M. O. Vysotsky and V. Bo¨hmer, Org. Lett., 2000, 2, 3571–3574.
14 Compare the synthesis of mixed methyl/propyl ethers: S. E. Matthews,
M. Saadioui, V. Bo¨hmer, S. Barboso, F. Arnaud-Neu, M.-J. Schwing-
Weill, A. Garcia Carrera and J.-F. Dozol, J. Prakt. Chem. (Weinheim,
Ger.), 1999, 341, 264–273.
15 A. Pop, M. O. Vysotsky, M. Saadioui and V. Bo¨hmer, Chem. Commun.,
2003, 1124–1125.
16 W. P. van Hoorn, W. J. Briels, J. P. M. van Duynhoven, F. C. J. M. van
Veggel and D. N. Reinhoudt, J. Org. Chem., 1998, 63, 1299–1308.
17 M. O. Vysotsky, O. Mogck, Y. Rudzevich, A. Shivanyuk, V. Bo¨hmer,
M. S. Brody, Y. L. Cho, D. M. Rudkevich and J. Rebek, Jr., J. Org.
Chem., 2004, 69, 6115–6120.
Kinetic studies
All the tetra-ureas 8 were dissolved in dichloromethane–ethanol
(100 : 1, v/v) and then passed through a 1 cm layer of silica. The
evaporated samples were solidified upon addition of methanol
(p.a.) and then pre-dried with a rotary evaporator first at
room temperature and then at 60 ◦C. The obtained powders of
monomeric 8 were kept in vacuo over P2O5 and solid NaOH for
1 week. Cyclohexane-d12 was dried over molecular sieves 3 A for
at least 4 weeks. Benzene was passed through a 1 cm layer of basic
Al2O3 and then kept over molecular sieves 3 A for 2 days. NMR
tubes, sample pipettes and flasks for kinetic runs were kept in vacuo
over P2O5 and NaOH for 2 days.
A sample of the monomeric 8 was weighted in a flask to give
finally a 2 mM solution of the respective dimer in the NMR tube
(4.89–5.86 mg of 8). Benzene (5 ml) was added and the solution
was kept at room temperature for 1 h. The solvent was evaporated
without heating, and the glassy mass of 8·C6H6·8 was dried in vacuo
over P2O5 and NaOH for 2–3 days. Cyclohexane-d12 (0.675 ml)
was added to the flask and, after 1 min, the clear solution was
transferred in one portion to the NMR tube, containing one piece
˚
˚
18 M. Kato, K. Komoda, A. Namera, Y. Sakai, S. Okada, A. Yamada,
K. Yokoyama, E. Migita, Y. Minobe and T. Tani, Chem. Pharm. Bull.,
1997, 45, 1767–1776.
19 R. A. Jakobi, V. Bo¨hmer, C. Gru¨ttner, D. Kraft and W. Vogt,
New J. Chem., 1996, 20, 493–501.
20 J.-D. van Loon, A. Arduini, L. Coppi, W. Verboom, A. Pochini, R.
Ungaro, S. Harkema and D. N. Reinhoudt, J. Org. Chem., 1990, 55,
5639–5646.
˚
of molecular sieve 3 A. The tube was stoppered with the cap
21 NMR spectra of homodimers of 8MMMP, 8MMPP, 8MPPP in C6D6 or
cyclohexane-d12 are too complicated for a description since mixtures of
regioisomeric dimers exist. Still, the characteristic patterns in the NH
region with the definite number of (partially overlapped) signals were
obtained; see pictures in the ESI† and ref. 15 for symmetry notation. In
THF-d8 these tetra-ureas exist in monomeric form but as mixtures of
conformers. 1H NMR spectra in THF-d8 were measured at +50, +25,
0, −25 and −50 ◦C and the data presented are taken from the best
resolved spectra. Nevertheless, from the ratio between CH3 signals of
pentyl groups at the narrow rim and those of 2-hexyloctyl groups at
the wide rim, the number of pentyl residues at the narrow rim can be
unambiguously concluded.
and covered with PARAFILM. The first NMR measurement was
performed exactly 10 min after the addition of cyclohexane-d12
to 8·C6H6·8. Normal H NMR spectra were acquired at 25 ◦C
1
with 32 scans accumulation. The total duration of one kinetic
measurement was 3 min 58 s, so for the rate calculations the middle
of this time interval was used. Between kinetic measurements
samples were thermostated at 25 ◦C. The guest exchange was
monitored by the integration of the same signals from 8·C6H6·8
and 8·C6D14·8. For each tetra-urea 8 at least 3 independent kinetic
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