Multiple catenanes based on tetraloop derivatives of calix[4]arenes

Article abstract of DOI:10.1016/j.tet.2008.10.099

Four novel tetraarylurea calix[4]arenes (4a-d) have been synthesized, substituted by ω-alkenyloxy residues in 3,5-positions of the arylurea residues. The eight alkenyl groups were pairwise connected by olefin metathesis and subsequent hydrogenation. The r

Full text of DOI:10.1016/j.tet.2008.10.099

Tetrahedron 65 (2009) 7220–7233
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Multiple catenanes based on tetraloop derivatives of calix[4]arenes
,
Olena Molokanova a, Ganna Podoprygorina a, Michael Bolte b, Volker Bo¨hmer a
*
a Johannes Gutenberg-Universita¨t, Duesbergweg 10-14, Mainz D-55099, Germany
b Johann Wolfgang von Goethe-Universita¨t, Marie Curie-Straße 11, Frankfurt/Main D-60439, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Four novel tetraarylurea calix[4]arenes (4a–d) have been synthesized, substituted by
u-alkenyloxy
Received 1 September 2008
Accepted 31 October 2008
Available online 5 November 2008
residues in 3,5-positions of the arylurea residues. The eight alkenyl groups were pairwise connected by
olefin metathesis and subsequent hydrogenation. The ring-closure reaction was carried out with het-
erodimers exclusively formed by 4 with a tetratosylurea calix[4]arene 1, which serves as a template in
this reaction step. The potential trans-cavity bridging is entirely suppressed in this way. Bis- and tet-
raloop calix[4]arenes cannot form dimers due to overlapping loops. However, they readily form hetero-
dimers with open-chain tetraureas, as long as their urea residues can pass through the loops. Thus, five
heterodimeric capsules 8a–e with bis[3]catenane structure were synthesized using again the olefin
metathesis followed by hydrogenation. Two different strategies were compared for this reaction se-
quence, starting with heterodimers formed either by tetraloop derivatives 5 with tetraalkenyl tetraureas
6 (pathway A) or by bisloop derivatives 7 with octaalkenyl tetraureas 4 (pathway B). A distinct advantage
of one of these pathways was not observed; the bis[3]catenanes were obtained with yields of 20–60%.
Heterodimers formed by tetraloop derivatives 5b–d and octaalkenyl ureas 4b–d were converted ana-
logous to three novel cyclic [8]catenanes 9a–c in 30–42% yield. The structure of the novel catenanes was
unambiguously proved by 1H NMR and ESI MS, and for 8a and 9a additionally by single crystal X-ray
analysis.
Dedicated to the memory of Dmitry
M. Rudkevich
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
toluene, chloroform, dichloromethane, etc. Their structure was first
deduced from the 1H NMR spectra22,23 and proved later by several
The synthesis of various interlocked structures (such as cate-
nanes, rotaxanes, knots,1 Borromean rings,2,3 etc.) is one of the most
attractive topics in modern organic or supramolecular chemistry.
Such compounds are interesting not only due to their topological
properties but also theycould find potential applications, e.g., for the
design of controlled molecular-level machines and motors.4,5 An
important factor for the synthesis of such intricate molecules is the
suitable preorganization of the reactive moieties to form selectively
the desired covalent connections. A suitable arrangement of the
functional groups in space can be achieved either by appropriate
covalent linkage6–8 or by reversible interactions,9 such as hydrogen
X-ray structures.24,25 The two calix[4]arene molecules in such a
dimer are turned by 45ꢀ with respect to each other allowing the
formation of a cyclic array of 16 intermolecular hydrogen bonds
between the NH and C]O groups of the interlocking urea functions
at their wide rim (see Fig. 1a).
The internal volume of the tetraurea capsules is about 190–
200 Å3.24 One molecule of the solvent is usually included as guest in
the
p-electron-rich cavity of the tetraurea dimer. It can be ex-
changed against other, more attractive guests, 26 e.g., neutral mol-
ecules (1,4-difluorobenzene)27 or cations of appropriate size
(tetraethylammonium,25 cobaltocenium28).
bonding,10–12
p
–p
interactions,13 or by coordination to metals14–18
In the presence of a polar solvent tetraurea dimers dis-assemble
to monomers, which don’t possess such host properties as the di-
meric capsules.
or anions.19,20 Among numerous self-assembly motives, also the
dimerization of calix[4]arenes bearing four urea functions at their
wide rim, has been utilized for the preparation of novel structures
with interesting topology and properties.21
2. Results and discussion
2.1. General considerations
Tetraurea derivatives of calix[4]arenes (further ‘tetraureas’)
form dimeric capsules in apolar, aprotic solvents, such as benzene,
In tetraurea dimers the residues attached to the calixarene
skeleton via the urea functions are specifically arranged in space. If
appropriate reactive groups are introduced to these residues,
* Corresponding author. Tel.: þ49 6131 3922319; fax: þ49 6131 3925419.
E-mail address: vboehmer@uni-mainz.de (V. Bo¨hmer).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.10.099

O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
7221
a
Y
C5H11
b
O
O
NH
NH
4
4
O
C
O
C
NH
R
NH
SO2
Tos
Y = alkyl
R = aryl
CH3
1
α
α
α
Tos
R
α'
β
R
R
R
R
R
R
R
R
R
R
R
R
R
R
Tos
Tos
R
'
Tos
β
α
Figure 1. (a) Side and top views of the tetraurea dimer (oxygen functions omitted). (b) Possible connections by ring-closure reactions within a tetraurea dimer, a monomer, and
a heterodimer with tetratosylurea 1.
intramolecular or intermolecular connections (
are possible between neighboring groups within a dimer. Addi-
tionally,
0-connections with remote functions have to be consid-
ered within a dimer, while an
0-connection should be possible only
a
- or
b
-connections)
reactions (
monomeric form, and makes only
a
0-connections), which are inevitable in the case of the
-connections possible. Conse-
a
b
quently, ring-closure reactions between the neighboring arms
within such a heterodimer should lead exclusively to compounds
containing ‘loop(s)’ between adjacent urea groups.
Recently, we have successfully used this heterodimerization for
the synthesis of various novel multi-macrocyclic tetraureas.31–33
Several examples with two, three, and four ‘loops’ (Fig. 2) were
prepared in good yields by the covalent connection of their adja-
cent alkenyl residues by metathesis reaction within the hetero-
dimer with 1.
a
in a monomeric calix[4]arene (Fig. 1b). This assumption was fully
confirmed by our early experiments in which the metathesis re-
action and subsequent hydrogenation were applied to the dimer of
a
tetra-m-(
expected isomers, the bis[2]catenane (four
doubly bridged mono[2]catenane (two - and two
and the tetra-bridged capsule (four -connections), could be iso-
u
-octenyloxy)phenylurea calix[4]arene.29 The three
a-connections), the
a
b
-connections),
b
lated. This first successful attempt inspired us to improve the se-
lectivity of the synthesis.
The exclusive formation of 1:1 heterodimers between tetrato-
sylurea calix[4]arene 1 and other tetraarylurea derivatives de-
scribed by Rebek et al.30 has provided us with a perfect template for
the highly selective synthesis of a family of novel macrocycles. In
these heterodimers, like in the tetraurea homodimers, residues
attached to the urea groups of both tetratosyl- and tetraarylurea
calixarenes are alternatingly entangled. Thus, reacting moieties
attached to tetraarylurea become separated in space by the tosyl
groups. This prevents automatically unfavored trans-cavity
Figure 2. Schematic representation of bis-, tris-, and tetramacrocyclic tetraurea ca-
lix[4]arenes obtained by
a-connections within the heterodimers formed between the
corresponding precursors and tetratosylurea 1.

7222
O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
COOH
O
O
(CH2)m
(CH2)m
3a-d
C5H11
C5H11
O
O
i), ii)
NH2
NH
NH
4
4
C
O
2
O
O
(CH2)m
(CH2)m
m = 3
m = 4
m = 6
m = 9
83%
95%
48%
57%
a
b
c
d
4a-d
Figure 3. The synthesis of the octaalkenyl precursors 4 for tetraloop compounds. (i) DPPA, Et3N, benzene, heating; (ii) benzene, heating.
Although these macrocyclic compounds possess four urea func-
catenanes34,35 by ring closure36 or to rotaxanes by stoppering re-
actions37 if the open-chain tetraurea bears appropriate reactive groups.
Obviously, variation of the length of the reacting alkenyl resi-
dues and the size of the loops may lead to combination(s) where
either the heterodimer (pseudo-rotaxane) cannot be formed or the
ring closure is impossible due to steric reasons. Thus, one of the
tions, they are not able to form homodimers due to the repulsion of
their overlapping ‘loops’. However, the multi-loop tetraureas readily
form heterodimers with open-chain tetraureas provided the re-
spective urea residues can pass through the loops. These heterodimers
can be considered as pseudo-rotaxanes. They can be converted to
Tos
Tos
i), ii)
Tos
Tos
Tos
Tos
Tos
Tos
p = 2•m + 2
(CH2)p
1•4
1•5
5
O
O
O
O
O
O
H
N
N
5a-d
C
H
H
C
N
H
N
p = 8
32%
80%
93%
88%
a
b
c
d
Y
O
O
O
O
Y
Y
(CH2)p
(CH2)p
p = 10
p = 14
p = 20
Y
O
O
H
N
N
C
H
H
C
N
N
H
O
O
O
Y = C5H11
O
(CH2)p
Figure 4. Schematic representation of the synthesis of tetraloop compounds 5a–d. (i) Grubbs’ catalyst, CH2Cl2, rt; (ii) H2, PtO2, THF, rt.

O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
7223
Approach A
n = 2•m + 2
Approach B
p = 2•m + 2
5•6
8
4•7
(CH2)n
C5H11
O
O
O
O
O
H
N
N
C
H
NH
NH
4
H
C
n = 8
a
b
c
d
N
N
O
C
m = 3
a
H
Y
n = 10
n = 14
n = 20
O
O
O
Y
m = 4
m = 6
m = 9
b
c
d
Y
Y
O
O
O
O
(CH2)m
H
N
N
C
H
H
C
N
N
H
O
6a-d
Y = C5H11
7a-d
O
(CH2)n
(CH2)n
O
8a-e
O
O
O
(CH2)p
H N
A
B
C
O
O
H
N
N
C
H
N
H
H
50%
n = p = 8
(CH2)p
a
b
c
d
e
C
N
N
H
O
O
O
O
O
35%
20%
49%
n = p = 10
n = p = 14
n = p = 20
47%
48%
33%
C
H
N
H
N
N
H
N
C
O
H
O
O
H
N
N
(CH2)p
C
H
H
C
N
H
N
N
H
O
O
C
n = 10; p = 8
60%
N H
(CH2)p
O
O
O
O
(CH2)n
Figure 5. Above: two strategies/approaches to synthesize bis[3]catenanes 8. Below: formula survey of tetraureas with four m-u-alkenyloxyphenyl groups 6a–d, bisloop macrocycles
7a–d, and bis[3]catenanes 8a–e and their yields by approaches A and B. Pentoxy groups in 8 are omitted for clarity.
goals of our present work is an exploration of the scope and the
limits for the synthesis of multiple catenanes derived from the
available tetraloop tetraureas. In addition, it is interesting to in-
vestigate the influence of mechanical connections within tetraurea
dimers on their host properties.
tetrapentylether 2 with isocyanates formed in situ via Curtius rear-
rangement from the corresponding acids in the presence of diphenyl-
phosphorylazide (DPPA) and triethylamine (Fig. 3). The resulting
octaalkenyl derivatives 4a–d (m¼3, 4, 6, 9) were purified by column
chromatography and/or recrystallization and isolated in 48–95% yields.
As evidenced by 1H NMR spectra tetraureas 4a–d easily form
homodimers and exclusively heterodimers with the tetratosylurea
1. This property was used for the preparation of tetraloop com-
pounds 5 by ring-closing olefin metathesis applied to the hetero-
dimers 1,4 in benzene solution (Fig. 4). To exclude complications by
2.2. Synthesis of tetraloop compounds
Tetraureas with eight alkenyl chains, the precursors for tetraloop
compounds, were preparedbyacylation of the tetraamino calix[4]arene

7224
O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
O
The significantly lower yield for the tetraloop compound 5a
NH
NH
(32%) is due to the formation of the stable tetrakis[2]rotaxane-like
structure 1,5a, which was also isolated and characterized as in-
dividual species.36 As mentioned before, the loops formed by ring-
closure reactions within the heterodimer 1,4a are too narrow in
this case to easily release the relatively bulky tosyl units of the
template 1. Nevertheless, during the hydrogenation in tetrahydro-
furan and the purification by column chromatography (ethyl ace-
tate/n-hexane, 1:7) the dissociation process slowly takes place,
allowing to isolate the tetraloop compound 5a in 32% yield.
The structure and the purity of compounds 3a–d, 4a–d, and 5a–
d were confirmed by 1H NMR spectroscopy and field-desorption
(FD) or electrospray ionization (ESI) mass spectrometry.
O
O
= ArH
O
NH
= ArH
bisloop
tetraloop
= ArH
skeleton
= NH
a
10.0
9.0
8.0
7.0
6.0
(ppm)
*
2.3. Synthesis of bis[3]catenanes
There are two possible pathways (Fig. 5) to prepare the bis[3]-
catenanes 8: one, starting from the heterodimers between tetra-
loops 5 and tetralkenyl tetraureas 6 (approach A) and another one,
starting with the heterodimers between bisloop compounds 7 and
octaalkenyl tetraureas 4 (approach B). The only example of
a bis[3]catenane 8 described previously was synthesized following
the approach A,34 while the second strategy B was not yet
attempted. Consequently, a general comparison of both strategies is
also lacking.
[CHCl3]
b
*
CHCl3
Tetraloop compounds 5a–d readily form heterodimers with
tetraureas 6a–d, bearing four
u-alkenyloxyphenyl groups. Ring-
closure by metathesis reaction followed by hydrogenation leads to
bis[3]catenanes 8a–d in 20–50% yield. The yields of these com-
pounds show no correlation with the length of the alkenyl residues
and the size of the loops; however, the procedure has not been
optimized for each single case. Reaction conditions were similar to
those published before:34,35 olefin metathesis was carried out in
dichloromethane solution under inert atmosphere using Grubbs’
catalyst (first generation). The resultant products were directly
hydrogenated in the presence of platinum dioxide.
Alternatively, the catenanes 8b–d were prepared in 33–48%
yield from heterodimers between bisloop macrocycles 7a–d and
octaalkenyl tetraureas 4b–d using the same reaction steps.
In the case of bisloop compound 7a (n¼8) and tetraurea 4a
(m¼3) the formation of heterodimers in dichloromethane solution
was not observed. This might be explained by sterical reasons. Most
probably, the 3,5-dialkenyloxyphenyl groups of the tetraurea 4a are
too voluminous to pass through the smallest loops of the series. In
fact compound 7b, which has loops larger only by two methylene
groups dimerizes easily with tetraurea 4a; ring closure of this
heterodimer led to the corresponding ‘hybrid’ bis[3]catenane 8e
(n¼10, p¼8) in 60% yield.
c
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5
(ppm)
Figure 6. Sections of the 1H NMR spectra (400 MHz, 25 ꢀC) of bis[3]catenane 8a (a) in
THF-d8, (b) with chloroform as guest in C6D6, and (c) with C6D6 as guest in C6D6. The
solvent peaks are marked by asterisk.
cis- and trans-isomers the double bonds in the products were di-
rectly hydrogenated in the presence of platinum dioxide as catalyst.
The macrocyclic compounds 5b–d were easily ‘liberated’ from the
tetratosylurea template by the addition of hydrogen bond breaking
solvents (e.g., tetrahydrofuran) and isolated in 80–93% yield.
*
a
*
By its topology a bis[3]catenane has C2v symmetry. The for-
mation of the hydrogen-bonded belt requires the orientation of
the urea groups, which reduces the symmetry to C2. This is
reflected by their NMR spectra in apolar solvents (CDCl3, CD2Cl2,
C6D6). However, the spectra of bis[3]catenanes 8a–e show a split-
ting of the signals, which is similar to that observed in apolar
solvents also in a polar solvent such as tetrahydrofuran-d8.
[Et4N+]
[Et4N+]
b
*
[Et4N+]
[Et4N+]
Table 1
c
Survey on the molecular peaks found by ESI MS for bis[3]catenanes 8a–e
10.0
9.0
8.0
7.0
6.0
(ppm)
0.0 -1.0 -2.0 -3.0
Bis[3]catenanes
Cations
Guests
Abundance (%)
8a
8b
8c
2Naþ
2 ꢂ acetonitrile
Tetrahydrofuranþethanol
Acetonitrile
Tetrahydrofuran
d
100
100
100
47
100
100
NaþþHþ
Figure 7. The inclusion of the tetraethylammonium cation in bis[3]catenane 8c
demonstrated by its 1H NMR spectra (400 MHz, 25 ꢀC) in CD2Cl2 (marked by asterisk).
(a) Spectrum of pure 8c, (b) the spectrum 3 min after addition of Et4NþPF6ꢁ (a mixture
of two complexes of 8c with CD2Cl2 and Et4Nþ as guests), and (c) the spectrum of 8c
with Et4Nþ as guest.
2Naþ
2Naþ
8d
8e
2Hþ
NaþþHþ
2 ꢂ acetonitrile

O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
7225
i), ii)
p = 2•m + 2
9
4•5
(CH2)p
O
O
O
O
(CH2)p
H N
O
O
C
O
O
H
N
N
C
H
N
9a-c
H
H
(CH2)p
C
N
N
(CH2)p
H
O
O
O
O
O
p = 10
p = 14
p = 20
a
32%
41%
40%
H
N
H
N
C
N
H
N
C
O
H
O
b
c
O
H
(CH2)p
N
N
(CH2)p
C
H
H
C
N
H
N
N
H
O
O
C
O
O
N H
(CH2)p
O
O
O
O
(CH2)p
Figure 8. The synthesis of [8]catenanes 9a–c (pentoxy groups at the phenolic oxygens of calix[4]arene skeletons are omitted for clarity). (i) Grubbs’ catalyst, dichloromethane, rt;
(ii) H2, PtO2, tetrahydrofuran, rt.
Figure 6a contains a representative part of a spectrum of com-
pound 8a recorded in THF-d8. With the help of COSY spectra it was
deduced that the signals for NH protons are split into two groups,
four singlets shifted downfield and four upfield. The signals for
the aromatic protons of calixarene skeletons and for the protons in
2,6-positions of the 3-alkoxyphenyl (bisloop) and 3,5-dialkoxy-
phenyl (tetraloop) units are also split and appear in the spectra as
pairs of m-coupled doublets. All these are typical signs for the
hydrogen-bonded ‘dimeric’ structure. Obviously, not only a com-
plete separation of the two calixarenes forming the catenane is
impossible, but also their individual solvatation. Thus, a hydrogen-
bonded capsule seems to be still the energetically most favored
structure for bis[3]catenanes in THF. The hydrogen-bonded belt
can be broken, however, by pyridine, where the two NH protons
appear as two somewhat broad signals separated by 0.06 ppm for
8c (n¼p¼14).
included guest was dissolved in C6D6 displayed already only the
signals for the catenane containing C6D6.
Due to their shorter interlocking loops the guest exchange is
relatively slow for the catenanes 8a and 8e and can be monitored by
NMR spectroscopy. For example, chloroform included in the cate-
nane 8a is completely replaced by the solvent C6D6, the more fa-
vored guest, in 40–46 h. A section of the 1H NMR spectrum of the
complex of 8a with chloroform in C6D6 is shown in Figure 6b. The
signal for the encapsulated chloroform is shifted upfield and ap-
pears at 5.13 ppm. The signals of the complex of 8a with deutero-
benzene as guest are slightly shifted in comparison to the complex
with chloroform (Fig. 6c). The appearance of the signal for the re-
leased chloroform at 6.13 ppm gives additional evidence for the
formation of the complex with C6D6. The complete exchange of
C6H6 against C6D6 in bis[3]catenanes 8a and 8e requires 7–8 days.38
The inclusion of a comparatively larger guest, such as the tet-
raethylammonium cation, in bis[3]catenanes was followed by 1H
NMR spectroscopy for compound 8c (n¼p¼14) in dichloromethane.
The signals for the capsules with tetraethylammonium appeared
immediately after the addition of the tetraammonium hexa-
fluorophosphate to the solution (Fig. 7). Like in the case of open-
chain tetraureas, the ethyl groups of the included cation have
pairwise different magnetic environments: two of them are within
the ‘equatorial plane’ (the plane of the hydrogen-bonded belt),
while the other two point toward the ‘poles’ of the capsule (the
The difference to bis[2]catenanes,35 which show a broad, un-
resolved spectrum in THF is most probably due to the fact that
the loops of the bisloop compound penetrate into two adjacent
loops in bis[3]catenanes, which obviously limits their mobility
drastically.
2.4. Guest inclusion of bis[3]catenanes
Like the dimers of open-chain tetraureas bis[3]catenanes 8a–e
include in their cavity small molecules as guest. For compounds
with relatively large loops (8b–d) the exchange of included ben-
zene or chloroform against benzene-d6 takes place within seconds.
The 1H NMR spectra recorded immediately after a sample with pre-
p
-basic cavity) and hence are much more shielded by the aromatic
rings.39 This is reflected in their spectra, where two characteristic
signals can be observed at high field at ꢁ0.13 and ꢁ3.27 ppm. The
complete exchange of the guest in 8c was achieved in 2 h.

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O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
ESI MS spectra for 8a–e have shown peaks for molecular ions
doubly charged by either two sodium cations, or two protons, or by
one sodium cation and one proton 1:1. Different guest molecules
were included (see Table 1) depending on the solvent for the
preparation of the samples. The number of guest molecules varies
between two (8a, 8b, 8e) and one (8c). For bis[3]catenane 8d only
the peak corresponding to ‘empty’ doubly charged species was
found by ESI MS. Obviously, compounds 8 release guest molecules
from their cavity with increasing size of the loops more easily.
*
a
*
2.5. Synthesis of [8]catenanes
Metathesis reaction of the heterodimers formed by the open-
chain octaalkenyl tetraureas 4b–d and the tetraloop calix[4]arenes
5b–d, followed by hydrogenation produced the pure [8]catenanes
9a–c in 32–41% yield (Fig. 8).
b
In the case of tetraloop 5b (p¼10) and tetraurea 4b (m¼4) we
met difficulties with the formation of their heterodimer under the
following standard conditions. Normally, stirring the solution of
both compounds (where 5b is taken in 5% excess) in dichloro-
methane at room temperature for 48 h is sufficient to complete the
dimerization of the derivatives with larger loops 5c (p¼14) and 5d
(p¼20) with the corresponding tetraureas 4c and 4d. However, for
the pair with shorter residues only the signals for the homodimer of
tetraurea 4b and broad unclear signals for the tetraloop 5b were
observed in the 1H NMR spectrum recorded in CD2Cl2 (Fig. 9a).
Stirring for further 48 h at room temperature led to the appearance
of some tiny signals of the heterodimer 4b,5b in the spectrum.
Refluxing the reaction mixture for 20 h resulted in a slight but in-
significant growth of these signals. This showed us that the for-
mation of the heterodimer 4b,5b is possible in principle (in
contrast to the heterodimer 4a,7a), however, it is kinetically hin-
dered due to steric reasons.
*
c
10.0
9.0
8.0
7.0
6.0
(ppm)
5.0
4.0
3.0
1
Figure 9. H NMR spectra (400 MHz, 25 ꢀC) in CD2Cl2 (marked by asterisk) of (a) the
dimer 4b,4b in the presence of tetraloop 5b, 48 h after mixing, (b) the heterodimer
4b,5b, formed after 16 days under reflux in dichloromethane/tetrahydrofuran solu-
tion, and (c) the resulting cyclic [8]catenane 9a.
formation of two kinds of hydrogen bonds (weaker and stronger) to
the neighboring urea groups and appear at 9.38–9.45 and
6.68–6.91 ppm. Two m-coupled doublets for the aryl protons of
calixarene skeletons were observed in COSY spectra at 7.74–7.76
and 5.68–5.89 ppm. The aromatic protons of the 3,5-dialkox-
yphenyl residues, which are adjacent to the urea functions are
inequivalent for the same reasons as the protons of calixarene
skeleton. They appear as m-coupled doublets at 7.50–7.72 and
Of course, the homodimer 4b,4b forms in solution much
more rapidly than the heterodimer 4b,5b, which requires that
four 3,5-dialkoxyphenyl residues of 4b are threaded through
the loops of 5b. For this sterically difficult process only the
very small (usually not detectable) concentration of ‘free’ 4b is
available.
This brought us to the idea that the formation of heterodimers
(the only dimers possible for the tetraloop compounds!) might be
accelerated by the weakening of the urea–urea hydrogen bonds.
Therefore, we added tetrahydrofuran (10 mL) to the solution of
tetraloop 5b and tetraurea 4b in dichloromethane (100 mL) and
kept it under reflux. The re-assembly process was regularly moni-
tored by the growth of the signals for the heterodimers in the 1H
NMR spectrum (CD2Cl2). Finally, as shown in Figure 9b, after 11
days the signals for the heterodimer became dominant in the so-
lution (although some tiny peaks of the signals for the homodimer
4b,4b could be still observed). An increase of the content of tet-
rahydrofuran (to 20 mL) in the reaction mixture followed by stir-
ring under reflux for further 11 days caused no changes in the 1H
NMR spectrum. Thus, the solution was evaporated, the resulting
pseudo-rotaxanes were re-dissolved in dichloromethane, and
subjected to olefin metathesis in the presence of Grubbs’ catalyst.
After hydrogenation, the corresponding [8]catenane 9a (32% yield)
and the unreacted tetraloop compound were separated from the
reaction mixture by column chromatography.
*
a
*
b
Et4N+
*
Et4N+(icl.)
2.6. Spectroscopic properties and guest inclusion
of [8]catenanes
c
10.0 9.0
8.0
7.0
6.0
5.0
(ppm)
4.0
3.0
0 -1.0 -2.0 -3.0
The 1H NMR spectra of [8]catenanes 9a–c in CD2Cl2 reflect the S8
symmetry of the molecules (see an example in Fig. 9c) and remind
of the spectra for homodimers of tetraureas 4a–d. The signals for
NH protons in 9a–c are also split into two singlets due to the
1
Figure 10. H NMR spectra (400 MHz, 25 ꢀC): (a) 9c in THF-d8; (b) 9c in CD2Cl2 and (c)
9c and 9c$Et4NþPF6ꢁ (marked by circles) in CD2Cl2 (the solvent peaks are marked by
asterisk).

O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
7227
Table 2
Comparison of some characteristic crystallographic data for the bis[3]catenane 8a
and the cyclic [8]catenane 9a
Dimer
8a
9a
Tetraester24
Planes of calix-O-atoms
Distance between centers [Å]
Angle [ꢀ]
12.692
4.59
12.938
5.99
12.487
0.0
Planes of methylene C atoms
(¼reference)
Distance between centers [Å]
Angle [ꢀ]
10.252
4.54
10.417
3.99
9.784
0.0
Planes of carbonyl C atoms
Distance between centers [Å]
Angle [ꢀ]
1.502
3.04
1.606
2.56
1.100
0.0
Calixarene Aa
O–O distance diagonal
5.188
3.647
7.163
7.155
10.227
11.253
73.2b
48.0b
69.5c
56.4c
5.166
3.649
7.112
7.267
9.831
11.370
73.4
55.0
73.5
50.8
4.376
C–C distance diagonal (reference
plane) [Å]
C–C distance diagonal (carbonyl
groups) [Å]
Angle calix-phenyl plane/ reference
plane [ꢀ]
62.4
Calixarene Ba,d
O–O distance diagonal [Å]
Figure 11. Side (left) and top (right) views of the X-ray structure of bis[3]catenane 8a
(n¼p¼8) and arrangement of the molecules in the crystal lattice. One molecule of
n-hexane is included in the cavity of the catenane. Pentyl residues at the phenolic
oxygens of calixarene skeletons and hydrogens are omitted.
5.076
3.813
7.466
7.035
10.330
11.130
70.6
5.057
3.732
7.127
7.256
10.809
10.391
69.1
4.469
C–C distance diagonal (reference
plane) [Å]
C–C distance diagonal (carbonyl
groups) [Å]
Angle calix-phenyl plane/reference
plane [ꢀ]
6.13 ppm. The proton in the p-position of the 3,5-dialkoxyphenyl
residues is observed as a broad singlet at 6.39–6.68 ppm.
64.1
54.2
59.0
Similar to bis[3]catenanes 8a–e, [8]catenanes 9a–c keep their
system of hydrogen bonds and stay as ‘hydrogen-bonded dimers’ in
polar solvent such as tetrahydrofuran. The stability of this system
was checked by NMR spectroscopy on [8]catenanes 9b and 9c,
which were kept in THF-d8 for more than one week and showed no
70.7
58.7
71.3
53.0
Data for the first crystal structure of a dimeric capsule of tetraurea calix[4]arenes are
included for comparison.
a
Two calixarenes per catenane.
b,c
Adjacent phenyl rings connected by the same loop.
d
Bisloop calixarene in 8a.
signs of ‘dissociation’ of the hydrogen-bonded capsule in their
spectra (see Fig. 10a in comparison to Fig. 10b).
The capsular structure with a hydrogen-bonded belt is stable
even in pyridine, where two sharp singlets for NH protons are
observed at 7.41 and 9.89 ppm for 9b (p¼14), a striking difference
to the bis[3]catenane 8c having the same size of the loops.
The inclusion of tetraethylammonium cation as guest was
attempted for [8]catenane 9b under the same conditions as for
bis[3]catenane 8c. Both compounds have an identical length of
the loops (n¼p¼14), however, they show a significant difference
in their host properties. As observed by 1H NMR spectrometry, the
cation inclusion for 8c was complete in 2 h, while it needs about
three weeks for [8]catenane 9b. Obviously this is due to steric
reasons. The growth of the signals in the spectra for the species
9b containing tetraethylammonium as guest is illustrated in
Figure 10c. It shows two sets of signals in the ratio 1:1 for 9c
still having a solvent molecule as guest and for the complex of
9c with the cation. The signals for the complex 9c$Et4Nþ (as
hexafluorophosphate) are marked by circles (compare with
the spectrum of 9b before the addition of Et4NþPF6ꢁ in
Fig. 10b). The signals for the methyl groups of the included tet-
raethylammonium cation appear as two broad singlets at ꢁ0.07
and ꢁ3.22 ppm.
The structure of [8]catenanes 9a–c was also proved by ESI
MS. The peaks detected with high abundance by ESI MS corre-
spond to the doubly charged (due to the presence of two sodium
cations) molecular ions of [8]catenanes 9a–c, all containing
Figure 12. Side (left) and top (right) views of the X-ray structure of [8]catenane 9a
(p¼10) and arrangement of the molecules in the crystal lattice. One molecule of n-
hexane is included in the cavity of the catenane. Pentyl residues at the phenolic
oxygens of calixarene skeletons and hydrogens are omitted.

7228
O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
surprisingly one tetrahydrofuran molecule. The latter is one of
the components of the solvent mixture, which was used for the
preparation of the samples for the experiments. Tetrahydrofu-
ran was obviously ‘imprisoned’ in the cavity of [8]catenanes as
guest and couldn’t escape under conditions of ESI MS
measurements.
For catenane 9a with the smallest loops (p¼10), besides the
dominant peak for the molecular ion with tetrahydrofuran (100%),
the peaks for doubly charged molecular ions with two molecules of
acetonitrile (45%) and one molecule of trifluoroacetic acid (12%),
which was added to all samples as a source of protons, were found.
This shows that guest exchange is possible even for such sterically
hindered structures as 9a.
dimer (5.076/3.813 and 5.188/3.647 Å for 8a and 5.057/3.733 and
5.166/3.649 Å for 9a) together with the angles between the planes
of the phenolic units and the reference plane of the methylene
carbons characterize quantitatively the oval-like deformation.
These angles (48–73ꢀ for 8a, and 51–74ꢀ for 9a) show, that both
catenanes have practically the same shape. The distortion for single
diphenylurea structures may be characterized by the interplanar
angle of the aromatic rings. It varies between 16.4ꢀ and 31.6ꢀ
(bisloop part) and 14.2ꢀ and 23.8ꢀ (tetraloop part) for 8a, and 14.3ꢀ
and 32.9ꢀ for 9a. In spite of these distortions the capsules are glued
together by a seam of strong intermolecular hydrogen bonds, in-
dicated by Nphenyl/Ocarbonyl distances between 2.787 and 2.900 Å
(8a) and 2.783 and 2.883 Å (9a).40
Surprisingly, one molecule of n-hexane is included as guest in
the cavity of the catenane 9a although usually tetraurea dimers
encapsulate (like 8a), other molecules, such as benzene, chloroform
and dichloromethane, which are used as ‘classic’ solvents for the
dimerization of tetraurea calix[4]arenes. Three dichloromethane
molecules are also present in the crystal lattice outside the dimeric
capsule, packed between disordered alkyl chains of the loops.
2.7. Crystal structures
Slow evaporation of the solution of bis[3]catenane 8a (n¼p¼8)
in chloroform/methanol and of [8]catenane 9a (p¼10) in
dichloromethane/n-hexane produced single crystals suitable for
X-ray analysis. The crystal structure reveals that in both cases the
‘dimeric’ system with a belt of hydrogen bonds is kept in the solid
state (Fig. 11 and Fig. 12), although for 8a a polar, hydrogen bond
breaking solvent (methanol) was used. However, in contrast to
a similar [8]catenane with larger loops (p¼14)34 both structures are
noticeably deformed.
Some characteristic angles and distances between atoms and
planes are collected for both structures in Table 2, and compared
with the first crystal structure of a hydrogen-bonded dimer of
a tetraurea calix[4]arene.24 Technical details and a summary of
crystallographic data are reported in Table 3.
In contrast to the C4 symmetrical reference both structures are
more or less distorted. The planes of the phenolic oxygens, of the
methylene bridge carbons, and of the carbonyl carbon atoms are
not parallel but tilted by 3.0–6.0ꢀ. The distances between the cen-
ters of these planes are insignificantly longer (0.40–0.63 Å).
For both catenanes the methylene bridges of the two calix[4]-
arenes form the corners of a (nearly) regular square. The diagonal
distances differ by 6% or less. Unequal diagonal distances between
the opposite phenolic oxygens for each single calixarene of the
3. Conclusion and outlook
Tetraarylurea calix[4]arenes in which adjacent phenylurea
residues are linked by four –(CH2)8–, –(CH2)10–, –(CH2)14–, and
–(CH2)20– loops were synthesized by ring-closing metathesis fol-
lowed by hydrogenation. The exclusive formation of heterodimers
between tetratosyl- and tetraarylureas substituted by two u-alkenyl
residues was successfully used to preorganize the reacting groups
and to avoid trans-cavity bridging. While the originally resulting
[4]rotaxanewas difficulttosplit intothetetraloopcalixarene and the
template for the smallest ring size (n¼8) the synthesis of calix[4]-
arenes with larger loops (longer (CH2) chains with n >20) should be
possible.
Since bis- and tetraloop tetraureas cannot form homodimers
they form exclusively heterodimers with open-chain tetraurea
calix[4]arenes. The reaction sequence olefin metathesis/hydroge-
nation applied to these heterodimers with tetraalkenyl or octaal-
kenyl tetraurea calix[4]arenes leads to various bis[3]catenanes on
two different pathways and to cyclic [8]catenanes. Again we faced
difficulties for calix[4]arenes with shorter loops (n¼8) since their
formation of heterodimers with bis-u-alkenyl tetraureas is obvi-
Table 3
ously sterically hindered. Reasonable yields were obtained, how-
ever, for loops with n¼10, 14, and 20, and [8]catenanes with larger
loops, including different loop sizes within the [8]catenane should
be possible too.
Crystal data and structure refinement
Compound
8a
9a
C410H530Cl30N32O56
7866.16
173
Triclinic
Pꢁ1
C120.5H170Cl3N8O16
2093.08
173
Monoclinic
P21/c
23.7409(6)
28.0178(11)
37.0435(11)
90
106.820(2)
90
23,586.0(13)
8
1.179
0.143
Formula weight
Temperature [K]
Crystal system
Space group
a [Å]
In contrast to simple hydrogen-bonded dimers of tetraurea
calix[4]arenes the multiple catenanes described offer the possibil-
ity for a (more or less) permanent inclusion of a guest, also in polar
solvents. The strength of this inclusion can be controlled by the
general structure (bis[2]catenanes, bis[3]catenanes, or [8]cate-
nanes) and especially by the length of the interlocking rings. The
easiness of the guest release may be modified also by the structure
of the interlocking rings and by their attachment to the calix[4]-
arene. Further combinations, for instance a multi-catenane formed
by a trisloop and a tetraloop calix[4]arene, are also possible.
17.964(2)
21.996(3)
28.534(4)
101.345(10)
106.437(9)
99.404(10)
10,311(2)
1
b [Å]
c [Å]
a
b
g
, [ꢀ]
[ꢀ]
[ꢀ]
V [Å3]
Z
Dcalcd [g cmꢁ3
]
1.267
0.267
m
(Mo K
a
) [mmꢁ1
]
4. Experimental
4.1. General
Reflections collected
Independent reflections
Observed reflections, [I>2
108,720
36,360
7232
36,360/382/1892
1.448
277,905
41,652
15,047
41,652/770/2639
1.133
s
(I)]
Data/restraints/parameters
Goodness of fit on F2
Solvents and all other chemicals were purchased from Acros,
Aldrich, and Lancaster, and used without further purification.
1H NMR spectra were recorded on a Bruker DRX400 Avance
instrument (at 400 MHz). FD and ESI mass spectra were measured
on a Finnigan MAT 8230 spectrometer and a Micromass Q-ToF
Final R indices [I>2
R indices (all data), R1, wR2
Largest diff.
peak and hole
CCDC deposition number
s
(I)], R1, wR2
0.2441, 0.4794
0.4552, 0.5533
2.306, ꢁ0.554
0.1503, 0.3669
0.2713, 0.4331
2.789, ꢁ0.747
699485
699484

O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
7229
Ultima3 instrument, respectively. Melting points are uncorrected.
p-Tetraamino calix[4]arene tetradecylether 1 and p-tosyltetraurea
The methylester (8.10 g, 17.1 mmol) was hydrolyzed in ethanol
(140 mL) with potassium hydroxide (4.89 g, 87.4 mmol) in H2O
(20 mL). Pure acid 3d was isolated as a white, wax-like solid; yield
tetrapentylether
5
were prepared according to published
procedures.41
7.41 g, 94%. Mp: 46–48 ꢀC; 1H NMR (CDCl3):
d
7.22 (d, 2H, J¼2.0 Hz,
ArH), 6.68 (t, 1H, J¼2.1 Hz, ArH), 5.90–5.75 (m, 2H, CH]CH2), 5.05–
4.85 (m, 4H, CH]CH2), 3.97 (t, 4H, J¼6.5 Hz, OCH2), 2.10–1.95 (m,
4H, CH2), 1.85–1.70 (m, 4H, CH2), 1.50–1.15 (m, 24H, CH2); MS (FD)
m/z: calcd for C19H26O4 (Mþ) 458.7, observed 458.6.
4.2. Synthesis of 3,5-di-(u-alkenyloxy)benzoic acids 3
4.2.1. Benzoic acid 3a
The mixture of 5-bromo-1-pentene (9.48 g, 60.5 mmol),
methyl-3,5-dihydroxy benzoate (4.62 g, 27.5 mmol), and K2CO3
(8.34 g, 60.5 mmol) in DMF (140 mL) was vigorously stirred at 55 ꢀC
for 24 h. Then DMF was removed in vacuo, and the residue was
partitioned between dichloromethane (2ꢂ120 mL) and water
(120 mL). The organic layer was separated, washed with water
(100 mL) and brine (100 mL), and dried (MgSO4). Evaporation of the
solvent gave the crude product as an oil. Purification by column
chromatography (silica gel, ethyl acetate/n-hexane, 4:70) furnished
the pure product as a viscous oil (6.43 g, 77%), which was used for
the next step without characterization.
4.3. Synthesis of octaalkenyl derivatives 4
4.3.1. Tetraurea 4a
A solution of 3,5-di-(5-pentenyloxy)benzoic acid 3a (0.30 g,
1.03 mmol), diphenylphosphorylazide (0.31 g, 0.25 mL, 1.1 mmol),
and triethylamine (0.12 g, 0.016 mL, 1.1 mmol) in toluene (20 mL)
was stirred for 2 h at 55 ꢀC. Tetraamino calix[4]arene 2 (0.132 g,
0.172 mmol) was added and the mixture was stirred for 2 h at 85 ꢀC.
Then the solvent was evaporated and the residue was triturated with
methanol. Thesolid wasfilteredoffanddriedtogivethepureproduct
as a gray powder; yield 0.272 g, 83%. The product can be additionally
purified by column chromatography (silica gel, ethyl acetate/hexane,
1:14) followed by reprecipitation from methanol/dichloromethane.
Mp238 ꢀC; 1H NMR (DMSO-d6): 8.29 (s, 4H, NH), 8.12 (s, 4H, NH), 6.76
(s, 8H, ArH), 6.51 (s, 8H, ArH), 6.04 (s, 4H, ArH), 5.90–5.71 (m, 8H,
CH]CH2), 5.09–4.86 (m, 16H, CH]CH2), 4.33 (d, 4H, J¼13.3 Hz,
ArCH2Ar), 3.82 (pseudot, 24H, J¼6.1 Hz, OCH2), 3.11 (d, 4H, J¼12.9 Hz,
ArCH2Ar), 2.19–2.05 (m, 16H, CH2), 1.88 (m, 8H, CH2), 1.80–1.66 (m,
16H, CH2),1.46–1.30 (m,16H, CH2), 0.93 (br t,12H, CH3); MS (ESI) m/z:
calcd for C116H152N8O16 (MNaþ) 1937.5, observed 1937.0.
Methyl-3,5-di-(5-pentenyloxy)benzoate (6.43 g, 21.1 mmol) was
dissolved in ethanol (170 mL) and mixed with the solution of po-
tassium hydroxide (6.03 g, 0.108 mol) in H2O (23 mL). The mixture
was stirred at room temperature for 2 h, evaporated in vacuo, and
the residue was partitioned between 5% HCl (130 mL) and ethyl
acetate (130 mL). The organic layer was washed with water (100 mL)
and brine (100 mL), and dried (MgSO4). Evaporation of the filtrate
gave the corresponding acid as a white, waxy solid; yield 5.15 g, 84%.
Mp: 58.5–59.5 ꢀC; 1H NMR (CDCl3):
d 11.7 (br s, 1H, COOH), 7.22 (d,
J¼2.3 Hz, 2H, ArH), 6.68 (t, J¼2.3 Hz, 1H, ArH), 5.90–5.82 (m, 2H,
CH]CH2), 5.11–5.00 (m, 4H, CH]CH2), 4.00 (t, J¼7.4 Hz, 4H, OCH2),
2.25 (m, 4H, CH2CH]CH2), 1.91 (m, 4H, –OCH2CH2); MS (FD) m/z:
calcd for C17H22O4 (Mþ) 290.4, observed 290.2.42
4.3.2. Tetraurea 4b
Prepared as described for 4a from 3,5-di-(6-hexenyloxy) benzoic
acid3b(1.25 g, 3.92 mmol), diphenylphosphorylazide(1.2 g, 0.96 mL,
4.3 mmol), triethylamine (0.43 g, 0.61 mL, 4.3 mmol) in toluene
(79 mL), and tetraamino calix[4]arene 2 (0.500 g, 0.654 mmol). Tet-
raurea 4b was obtained as a powder; yield 1.264 g, 95%. Additional
purification was carried out by column chromatography (silica gel,
ethyl acetate/n-hexane, 1:22) followed by reprecipitation from
methanol/dichloromethane. Mp 235 ꢀC; 1H NMR (DMSO-d6): 8.27 (s,
4H, NH), 8.12 (s, 4H,NH), 6.76(s, 8H, ArH), 6.50(s, 8H,ArH), 6.03(s, 4H,
ArH), 6.00–5.68 (m, 8H, CH]CH2), 5.10–4.83 (m,16H, CH]CH2), 4.33
(d, 4H, J¼12.5 Hz, ArCH2Ar), 3.82 (m, 24H, OCH2), 3.11 (d, 4H,
J¼11.0 Hz, ArCH2Ar), 2.13–1.98 (m, 16H, CH2), 1.88 (m, 8H, CH2), 1.74–
1.56(m,16H, CH2),1.54–1.30(m, 32H, CH2),0.93(s,12H, CH3);MS(ESI)
m/z: calcd for C124H168N8O16 (MNaþ) 2049.7, observed 2049.1.
4.2.2. Benzoic acid 3b
Methyl-3,5-di-(6-hexenyloxy)benzoate was obtained as de-
scribed for 3a from 6-bromo-1-hexene (7.48 g, 43.6 mmol), methyl-
3,5-dihydroxy benzoate (3.51 g, 20.8 mmol), and K2CO3 (6.33 g,
45.9 mmol) in DMF (105 mL); yield 5.53 g, 80%.
The methylester (5.53 g, 16.6 mmol) was hydrolyzed in ethanol
(140 mL) with potassium hydroxide (4.75 g, 84.8 mmol) in H2O
(18 mL). Pure 3b was isolated as a white, wax-like solid; yield
4.43 g, 84%. Mp: 61 ꢀC; 1H NMR (CDCl3):
d
7.24 (d, 2H, J¼2.4 Hz,
ArH), 6.70 (t, 1H, J¼2.4 Hz, ArH), 5.90–5.82 (m, 2H, CH]CH2), 5.10–
5.00 (m, 4H, CH]CH2), 4.00 (t, 4H, J¼6.5 Hz, OCH2), 2.20–2.10 (m,
4H, CH2), 1.90–1.75 (m, 4H, CH2), 1.60 (m, 4H, CH2); MS (FD) m/z:
calcd for C19H26O4 (Mþ) 318.4, observed 318.3.
4.3.3. Tetraurea 4c
4.2.3. Benzoic acid 3c
Prepared as described for 4a from 3,5-di-(8-octenyloxy)benzoic
acid 3c (1.47 g, 3.92 mmol), diphenylphosphorylazide (1.19 mL,
4.31 mmol), triethylamine (0.436 g, 4.31 mmol), and tetraamino
calix[4]arene 2 (0.500 g, 0.654 mmol). The crude product was pu-
rified bycolumn chromatography (silica gel, ethyl acetate/n-hexane,
1:20) followed by reprecipitation from methanol/dichloromethane.
Pure 4c was obtained as a colorless powder; yield 0.714 g, 48%. Mp
232 ꢀC; 1H NMR (DMSO-d6): 8.27 (s, 4H, NH), 8.11 (s, 4H, NH), 6.76 (s,
8H, ArH), 6.49 (d, 8H, J¼1.7 Hz, ArH), 6.01 (br t, 4H, ArH), 5.83–5.71
(m, 8H, CH]CH2), 5.03–4.88 (m, 16H, CH]CH2), 4.33 (d, 4H,
J¼13.3 Hz, ArCH2Ar), 3.80 (pseudo t, 24H, J¼6.0 Hz, OCH2), 3.11 (d,
4H, J¼12.3 Hz, ArCH2Ar), 2.04–1.95 (m, 16H, CH2), 1.89 (m, 8H, CH2),
1.63 (m,16H, CH2),1.45–1.22 (m, 64H, CH2), 0.93 (br t,12H, J¼6.8 Hz,
CH3); MS (ESI) m/z: calcd for C140H200N8O16 (MHþ) 2252.2, observed
2251.5; (Mþ2Hþ) 1126.6, observed 1126.3.
Methyl-3,5-di-(8-octenyloxy)benzoate was prepared as de-
scribed for 3a from 8-bromo-1-octene (10.0 g, 52.6 mmol), methyl-
3,5-dihydroxy benzoate (4.02 g, 23.9 mmol), and K2CO3 (7.26 g,
52.6 mmol) in DMF (120 mL); yield 8.24 g, 89%.
The methylester (8.24 g, 21.2 mmol) was hydrolyzed in ethanol
(175 mL) with potassium hydroxide (6.06 g, 108 mmol) in H2O
(25 mL). Pure 3c was isolated as a white, waxy solid; yield 7.36 g,
93%. Mp: 39–43 ꢀC; 1H NMR (CDCl3):
d 11.7 (br s, 1H, COOH), 7.23 (d,
2H, J¼2.3 Hz, ArH), 6.69 (t, 1H, J¼2.2 Hz, ArH), 5.90–5.75 (m, 2H,
CH]CH2), 5.00–4.95 (m, 4H, CH]CH2), 4.00 (t, 4H, J¼7.4 Hz, OCH2),
2.07 (m, 4H, CH2), 1.79 (m, 4H, CH2), 1.50–1.35 (m, 12H, CH2); MS
(FD) m/z: calcd for C23H34O4 (Mþ) 374.5, observed 374.3.
4.2.4. Benzoic acid 3d
Methyl-3,5-di-(11-undecenyloxy)benzoate was prepared as
described for 3a from 11-bromo-1-octene (9.51 g, 38.8 mmol),
methyl-3,5-dihydroxy benzoate (2.96 g, 17.6 mmol), and K2CO3
(5.35 g, 38.8 mmol) in DMF (90 mL); yield 8.10 g, 97%.
4.3.4. Tetraurea 4d
Prepared as described for 4a from 3,5-di-(11-undecenyloxy)-
benzoic acid 3d (1.798 g, 3.921 mmol), diphenylphosphorylazide

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O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
(1.2 g, 0.96 mL, 4.3 mmol), triethylamine (0.43 g, 0.61 mL,
4.3 mmol), and tetraamino calix[4]arene 2 (0.500 g, 0.654 mmol).
Purification was carried out by column chromatography (silica gel,
tetrahydrofuran/n-hexane, 1:25) followed by reprecipitation from
methanol/dichloromethane. Pure 4d was obtained as a colorless
powder; yield 0.967 g, 57%. Mp 229 ꢀC; 1H NMR (THF-d8): 7.50 (s,
4H, NH), 7.43 (s, 4H, NH), 6.79 (s, 8H, ArH), 6.57 (d, 8H, J¼1.7 Hz,
ArH), 6.01 (br t, 4H, J¼2.0 Hz, ArH), 5.84–5.71 (m, 8H, CH]CH2),
5.00–4.83 (m, 16H, CH]CH2), 4.43 (d, 4H, J¼12.9 Hz, ArCH2Ar), 3.87
(t, 8H, J¼7.3 Hz, OCH2), 3.79 (t, 16H, J¼6.5 Hz, OCH2), 3.07 (d, 4H,
J¼13.3 Hz, ArCH2Ar), 2.07–1.98 (m, 16H, CH2), 1.94 (m, 8H, CH2),
1.75–1.63 (m under the solvent peak, 16H, CH2), 1.48–1.23 (m, 112H,
CH2), 0.96 (t, 12H, J¼6.8 Hz, CH3); MS (ESI) m/z: calcd for
C164H248N8O16 (MNaþ) 2610.8, observed 2610.8; (Mþ2Naþ) 1316.9,
observed 1316.4.
powder; yield 0.267 g, 93%. Mp >270 ꢀC (decomposition); 1H NMR
(THF-d8): 7.56 (s, 4H, NH), 7.47 (s, 4H, NH), 6.86 (s, 8H, ArH), 6.57 (s,
8H, ArH), 6.01 (s, 4H, ArH), 4.44 (d, 4H, J¼13.7 Hz, ArCH2Ar), 3.94–
3.70 (m, 24H, OCH2), 3.07 (d, 4H, J¼13.3 Hz, ArCH2Ar), 1.96 (m, 8H,
CH2), 1.80–1.60 (m under the solvent peak, 16H, CH2), 1.50–1.10 (m,
96H, CH2), 0.97 (t, 12H, J¼7.0 Hz, CH3); MS (ESI) m/z: calcd for
C132H192N8O16 (MHþ) 2148.0, observed 2147.4; (Mþ2Hþ) 1074.5,
observed 1074.2.
4.4.4. Tetraloop 5d
Tetratosylurea 1 (0.2702 g, 0.1739 mmol), tetraurea 4d (0.300 g,
0.116 mmol), Grubbs’ catalyst (0.0381 g, 0.0464 mmol) in dichlo-
romethane (480 mL), triethylamine (1.5 mL), and platinum dioxide
(83% Pt, 0.047 g, 0.21 mmol) in THF (25 mL) were reacted as de-
scribed for 5a. Purification by column chromatography (silica gel,
THF/n-hexane, 1:2) followed by reprecipitation from chloroform/
methanol gave the desired tetraloop calix[4]arene 5d as a colorless
powder; yield 0.252 g, 88%. Mp 160 ꢀC; 1H NMR (THF-d8): 7.51 (s,
4H, NH), 7.43 (s, 4H, NH), 6.82 (s, 8H, ArH), 6.57 (s, 8H, ArH), 6.01 (s,
4H, ArH), 4.44 (d, 4H, J¼13.3 Hz, ArCH2Ar), 3.96–3.69 (m, 24H,
OCH2), 3.07 (d, 4H, J¼13.6 Hz, ArCH2Ar),1.94 (m, 8H, CH2), 1.80–1.60
(m under the solvent peak,16H, CH2),1.50–1.20 (m,144H, CH2), 0.96
(br t, 12H, J¼6.8 Hz, CH3); MS (ESI) m/z: calcd for C156H240N8O16
(Mþ2Hþ) 1242.8, observed 1242.4.
4.4. Synthesis of tetraloop derivatives 5
4.4.1. Tetraloop 5a
Tetratosylurea 1 (0.243 g, 0.157 mmol) and tetraurea 4a (0.20 g,
0.105 mmol) were dissolved in dichloromethane (320 mL) and
stirred for 8 h at room temperature. The mixture was purged with
nitrogen for 30 min, Grubbs’ catalyst (34 mg, 0.042 mmol) was
added, and then stirring was continued for 48 h at room temper-
ature under nitrogen. Then triethylamine (1.0 mL) was added to
destroy the catalyst and the complex with tetratosylurea 1. After
1 h, the solvent was evaporated, the residue was dissolved in THF,
and the solvent was evaporated again. The crude product was hy-
drogenated in THF (20 mL) for 24 h (room temperature, normal
pressure) using platinum dioxide (83% Pt, 43 mg, 0.19 mmol) as
catalyst. The residue obtained by evaporation was purified by col-
umn chromatography (silica gel, ethyl acetate/n-hexane, 1:7). After
reprecipitation from chloroform/methanol, the desired tetraloop
calix[4]arene 5a was finally obtained as a colorless powder; yield
61 mg, 32%. Mp >310 ꢀC (decomposition); 1H NMR (THF-d8): 7.60
(s, 4H, NH), 7.53 (s, 4H, NH), 6.90 (s, 8H, ArH), 6.54 (s, 8H, ArH), 5.99
(s, 4H, ArH), 4.44 (d, 4H, J¼12.5 Hz, ArCH2Ar), 3.94–3.76 (m, 24H,
OCH2), 3.07 (d, 4H, J¼12.5 Hz, ArCH2Ar), 2.14–1.92 (m, 8H, CH2),
1.78–1.60 (m, 16H, CH2), 1.50–1.20 (m, 48H, CH2), 0.98 (t, 12H,
J¼6.5 Hz, CH3); MS (ESI) m/z: calcd for C108H144N8O16 (MHþ) 1811.4,
observed 1811.1; (Mþ2Hþ) 906.2, observed 906.1.
4.5. Synthesis of bis[3]catenanes 8
4.5.1. Approach A (starting from tetraloop compounds 5 and
tetraalkenyl derivatives 6)
A solution of the respective compounds 5 and 6 in freshly dis-
tilled and degassed dichloromethane was stirred at room temper-
ature for 48 h; the complete formation of the heterodimer was
verified by 1H NMR. When the signals of the homodimer had dis-
appeared, the reaction mixture was purged with nitrogen for
30 min and a solution of Grubbs’ catalyst was added. After 48 h of
stirring, triethylamine was added, the solution was stirred for 1 h,
and evaporated. The crude product was dissolved in THF, and hy-
drogenated for 4 h (room temperature, normal pressure) using
platinum dioxide (83% Pt) as catalyst. The crude product obtained
by evaporation was finally purified by column chromatography
followed by recrystallization.
4.4.2. Tetraloop 5b
4.5.2. Approach B (starting from bisloop compounds 7 and
octaalkenyl derivatives 4)
A solution of the respective compounds 4 and 7 was reacted as
described in approach A.
Tetratosylurea 1 (0.345 g, 0.222 mmol), tetraurea 4b (0.300 g,
0.148 mmol), Grubbs’ catalyst (49 mg, 0.059 mmol) in dichloro-
methane (600 mL), triethylamine (1.5 mL), and platinum dioxide
(83% Pt, 0.0605 g; 0.266 mmol) in THF (25 mL) were reacted as
described for 5a. Purification by column chromatography (silica gel,
THF/n-hexane, 1:3) followed by reprecipitation from chloroform/
methanol gave the desired tetraloop calix[4]arene 5b as a colorless
powder; yield 0.228 g, 80%. Mp >300 ꢀC (decomposition); 1H NMR
(THF-d8): 7.51 (s, 8H, NH), 6.89 (s, 8H, ArH), 6.56 (s, 8H, ArH), 6.00 (s,
4H, ArH), 4.44 (d, 4H, J¼12.6 Hz, ArCH2Ar), 3.94–3.76 (m, 24H,
OCH2), 3.08 (d, 4H, J¼12.9 Hz, ArCH2Ar),1.99 (m, 8H, CH2), 1.75–1.62
(m, 16H, CH2), 1.50–1.20 (m, 64H, CH2), 0.97 (t, 12H, J¼6.5 Hz, CH3);
MS (ESI) m/z: calcd for C116H160N8O16 (MHþ) 1923.6, observed
1923.2; (Mþ2Hþ) 962.3, observed 962.1.
4.5.3. Bis[3]catenane 8a
Approach A: starting with tetraloop compound 5a (58.0 mg,
0.0320 mmol), tetraalkenyl tetraurea 6a (0.0459 g, 0.0291 mmol)
in dichloromethane (120 mL), and Grubbs’ catalyst (14.4 mg,
0.0175 mmol). Hydrogenation in THF (20 mL) using platinum di-
oxide (83% Pt, 5.9 mg; 0.0261 mmol). The final purification was
achieved by column chromatography (silica gel, THF/n-hexane,
1:12; followed by THF/n-hexane, 1:6); recrystallization from chlo-
roform/methanol gave the bis[3]catenane 8a as a colorless, crys-
talline powder; yield 49 mg, 50%. Mp >320 ꢀC (decomposition); 1H
NMR (C6D6): 10.13 (s, 2H, NH), 10.10 (s, 2H, NH), 10.02 (s, 2H, NH),
9.89 (s, 2H, NH), 8.58 (s, 2H, ArH), 8.35 (d, 2H, J¼8.4 Hz, ArH), 8.27
(s, 2H, ArH), 8.18 (d, 2H, J¼2.2 Hz, ArH), 8.11 (d, 2H, J¼2.2 Hz, ArH),
8.09 (s, 2H, ArH), 8.07 (d, 2H, J¼1.8 Hz, ArH), 7.86 (d, 2H, J¼2.2 Hz,
ArH), 7.58 (s, 2H, ArH), 7.52 (s, 2H, NH), 7.40 (s, 2H, ArH), 7.35 (d, 2H,
J¼8.0 Hz, ArH), 7.30–7.00 (m under the solvent peak, 6H, ArH), 6.83
(s, 2H, NH), 6.82 (s, 2H, NH), 6.81 (s, 2H, NH), 6.73 (dd, 2H, J¼8.3 Hz,
J¼1.6 Hz, ArH), 6.62–6.55 (m, 4H, ArH), 6.52 (s, 2H, ArH), 6.32 (d, 2H,
J¼2.2 Hz, ArH), 6.06 (d, 2H, J¼1.8 Hz, ArH), 6.04 (d, 2H, J¼2.2 Hz,
4.4.3. Tetraloop 5c
Tetratosylurea 1 (0.311 g, 0.200 mmol), tetraurea 4c (0.300 g,
0.133 mmol), Grubbs’ catalyst (44 mg, 0.0533 mmol) in dichloro-
methane (540 mL), triethylamine (2 mL), and platinum dioxide
(83% Pt, 0.0545 g, 0.240 mmol) in THF (25 mL) were reacted as
described for 5a. Purification by column chromatography (silica gel,
THF/n-hexane, 1:2) followed by reprecipitation from chloroform/
methanol gave the desired tetraloop calix[4]arene 5c as a colorless

O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
7231
ArH), 6.01 (d, 2H, J¼2.2 Hz, ArH), 4.59 (d, 2H, J¼11.7 Hz, ArCH2Ar),
4.56–4.46 (m, 6H, ArCH2Ar), 4.30–4.02 (m, 12H, OCH2), 3.92–3.60
(m, 28H, OCH2), 3.29 (d, 2H, J¼12.1 Hz, ArCH2Ar), 3.24 (d, 2H,
J¼11.7 Hz, ArCH2Ar), 3.14 (d, 2H, J¼11.4 Hz, ArCH2Ar), 3.13 (d, 2H,
J¼11.7 Hz, ArCH2Ar), 2.20–1.65 (m, 26H, CH2), 1.55–1.09 (m, 82H,
CH2), 1.06–0.89 (m, 24H, CH3); MS (ESI) m/z: calcd for
C200H260N16O28 (Mþ2Naþþ2CH3CN) 1732.2, observed 1732.0.
7.90 (d, 2H, J¼2.2 Hz, ArH), 7.44 (m, 4H, NH, ArH), 7.40 (s, 2H, NH),
7.35 (m, 2H, ArH), 7.90–7.00 (m under the solvent peak, 12H, NH,
ArH), 6.62 (dd, 2H, J¼8.4, 1.7 Hz, ArH), 6.48–6.33 (m, 12H, ArH), 6.30
(d, 2H, J¼2.2 Hz, ArH), 4.54 (d, 2H, J¼12.0 Hz, ArCH2Ar), 4.48 (d, 2H,
J¼11.7 Hz, ArCH2Ar), 4.47 (d, 2H, J¼11.4 Hz, ArCH2Ar), 4.39 (d,
2H, J¼11.4 Hz, ArCH2Ar), 3.96–3.50 (m, 40H, OCH2), 3.33 (d, 2H,
J¼12.4 Hz, ArCH2Ar), 3.28 (d, 2H, J¼12.1 Hz, ArCH2Ar), 3.21 (d, 2H,
J¼12.4 Hz, ArCH2Ar), 3.20 (d, 2H, J¼11.4 Hz, ArCH2Ar), 2.15–1.87 (m,
16H, CH2), 1.74–1.02 (m, 160H, CH2), 0.98 (t, 12H, J¼7.3 Hz, CH3),
0.97 (t, 12H, J¼7.3 Hz, CH3); MS (ESI) m/z: calcd for C236H332N16O28
(Mþ2NaþþCH3CN) 1963.8, observed 1963.8; (Mþ2NaþþTHF)
1979.3, observed 1979.4.
4.5.4. Bis[3]catenane 8b
Approach A: starting with tetraloop compound 5b (80.0 mg,
0.0416 mmol), tetraalkenyl tetraurea 6b (64.7 mg, 0.0396 mmol) in
dichloromethane (160 mL), Grubbs’ catalyst (6.5 mg, 0.0079 mmol),
and triethylamine (0.5 mL). Hydrogenation in THF (20 mL) using
platinum dioxide (83% Pt, 8.0 mg, 0.036 mmol). The final puri-
fication by column chromatography (silica gel, THF/n-hexane, 1:15)
followed by recrystallization from chloroform/methanol gave
the bis[3]catenane 8b as a colorless, crystalline powder; yield
48.1 mg, 35%.
4.5.6. Bis[3]catenane 8d
Approach A: starting with tetraloop compound 5d (0.1362 g,
0.0548 mmol), tetraalkenyl tetraurea 6d (0.10 g, 0.0522 mmol) in
dichloromethane (211 mL), Grubbs’ catalyst (8.6 mg, 0.0104 mmol),
and triethylamine (1 mL). Hydrogenation in THF (20 mL) using
platinum dioxide (83% Pt, 10.6 g; 0.0470 mmol). The final purifi-
cation by column chromatography (silica gel, THF/n-hexane, 1:35)
followed by recrystallization from chloroform/methanol gave the
bis[3]catenane 8d as a colorless, crystalline powder; yield 0.112 g,
49%.
Approach B: starting with bisloop compound 7b (65.6 mg,
0.0414 mmol), octaalkenyl tetraurea 4b (0.0800 g, 0.0395 mmol)
in dichloromethane (160 mL), Grubbs’ catalyst (13.0 mg,
0.0158 mmol), and triethylamine (0.5 mL). Hydrogenation in THF
(20 mL) using platinum dioxide (83% Pt, 16.0 mg; 0.0713 mmol).
The final purification by column chromatography (silica gel, THF/n-
hexane, 1:15) followed by recrystallization from chloroform/
methanol gave the bis[3]catenane 8b as a colorless, crystalline
powder; yield 65.6 mg, 47%. Mp >280 ꢀC (decomposition); 1H NMR
(C6D6): 10.11 (s, 2H, NH), 10.06 (s, 2H, NH), 10.03 (s, 2H, NH), 10.00
(s, 2H, NH), 8.48 (s, 2H, ArH), 8.40 (d, 2H, J¼7.8 Hz, ArH), 8.28 (d, 2H,
J¼2.0 Hz, ArH), 8.23 (s, 2H, ArH), 8.16 (s, 2H, ArH), 8.10 (d, 2H,
J¼2.0 Hz, ArH), 8.07 (d, 2H, J¼1.7 Hz, ArH), 8.06 (d, 2H, J¼2.4 Hz,
ArH), 7.59 (s, 2H, ArH), 7.52 (s, 2H, NH), 7.38 (s, 2H, ArH), 7.27 (d, 2H,
J¼8.5 Hz, ArH), 7.22–7.07 (m under the solvent peak, 10H, NH, ArH),
7.05 (s, 2H, NH), 6.82 (s, 2H, NH), 6.71 (d, 2H, J¼8.2 Hz, ArH), 6.58 (s,
2H, ArH), 6.53 (dd, 2H, J¼7.8, 1.4 Hz, ArH), 6.48 (s, 2H, ArH), 6.43 (d,
2H, J¼2.0 Hz, ArH), 6.32 (d, 2H, J¼2.0 Hz, ArH), 6.27 (d, 2H, J¼2.4 Hz,
ArH), 6.25 (d, 2H, J¼2.4 Hz, ArH), 4.53 (d, 2H, J¼11.6 Hz, ArCH2Ar),
4.50 (d, 4H, J¼11.9 Hz, ArCH2Ar), 4.40 (d, 2H, J¼11.6 Hz, ArCH2Ar),
4.14–3.49 (m, 40H, OCH2), 3.31 (d, 2H, J¼11.9 Hz, ArCH2Ar), 3.29 (d,
2H, J¼11.9 Hz, ArCH2Ar), 3.16 (d, 2H, J¼11.9 Hz, ArCH2Ar), 3.15 (d,
2H, J¼11.9 Hz, ArCH2Ar), 2.11 (m, 4H, CH2), 1.97 (m, 12H, CH2), 1.81–
1.60 (m, 16H, CH2), 1.57–1.00 (m, 92H, CH2), 0.97 (t, 24H, J¼7.3 Hz,
CH3); MS (ESI) m/z: calcd for C212H284N16O28 (MHþþNaþþ
THFþEtOH) 1816.4, observed 1816.1.
Approach B: starting with bisloop compound 7d (75.2 mg,
0.0406 mmol), octaalkenyl tetraurea 4d (0.10 g, 0.0386 mmol) in
dichloromethane (150 mL), Grubbs’ catalyst (0.0127 g, 0.0154 mmol),
and triethylamine (1 mL). Hydrogenation in THF (20 mL) using
platinum dioxide (83% Pt, 15.8 mg; 0.0695 mmol). The final purifi-
cation by column chromatography (silica gel, THF/n-hexane, 1:25)
followed by recrystallization from chloroform/methanol gave the
bis[3]catenane 8d as a colorless crystalline powder; yield 56.4 mg,
33%. Mp >130 ꢀC (decomposition); 1H NMR (C6D6): 10.03 (s, 8H,
NH), 8.24 (d, 2H, J¼2.2 Hz, ArH), 8.20 (d, 2H, J¼1.9 Hz, ArH), 8.18 (d,
2H, J¼9.2 Hz, ArH), 8.14 (s, 6H, ArH), 8.06 (s, 2H, ArH), 8.00 (s, 2H,
ArH), 7.69 (s, 2H, ArH), 7.61 (d, 2H, J¼8.0 Hz, ArH), 7.39 (s, 2H, ArH),
7.31 (s, 2H, ArH), 7.30 (s, 2H, NH), 7.21 (s, 2H, NH), 7.19–7.05 (m
under the solvent peak, 8H, ArH, NH), 6.60 (dd, 2H, J¼8.3, 1.9 Hz,
ArH), 6.53 (dd, 2H, J¼8.6,1.6 Hz, ArH), 6.48 (s, 2H, ArH), 6.43 (s,
2H, ArH), 6.38 (s, 4H, ArH), 6.30 (d, 2H, J¼1.6 Hz, ArH), 6.28 (d, 2H,
J¼2.2 Hz, ArH), 4.62–4.47 (m, 8H, ArCH2Ar), 3.97–3.60 (m, 40H,
OCH2), 3.42 (d, 2H, J¼11.4 Hz, ArCH2Ar), 3.38 (d, 2H, J¼10.5 Hz,
ArCH2Ar), 3.34 (d, 2H, J¼10.8 Hz, ArCH2Ar), 3.27 (d, 2H, J¼11.4 Hz,
ArCH2Ar), 2.20–1.95 (m, 16H, CH2), 1.70–1.08 (m, 232H, CH2), 1.05–
0.96 (m, 24H, CH3); MS (ESI) m/z: calcd for C272H404N16O28
(Mþ2Hþ) 2174.2, observed 2174.0.
4.5.5. Bis[3]catenane 8c
Approach A: starting with tetraloop compound 5c (51.6 mg,
0.0240 mmol), tetraalkenyl tetraurea 6c (40.0 mg, 0.0229 mmol) in
dichloromethane (92 mL), Grubbs’ catalyst (3.8 mg, 0.0046 mmol),
and triethylamine (0.5 mL). Hydrogenation in THF (20 mL) using
platinum dioxide (83% Pt, 4.7 mg; 0.021 mmol). The final purifica-
tion by column chromatography (silica gel, THF/n-hexane, 1:20)
followed by recrystallization from chloroform/methanol gave the
bis[3]catenane 8c (0.0176 g, 20% yield) as a colorless, crystalline
powder.
4.5.7. Bis[3]catenane 8e
Approach B: starting with bisloop compound 7b (70.0 mg,
0.0442 mmol), octaalkenyl tetraurea 4a (80.7 mg, 0.0421 mmol)
in dichloromethane (170 mL), Grubbs’ catalyst (13.8 mg,
0.0168 mmol), and triethylamine (1 mL). Hydrogenation in THF
(20 mL) using platinum dioxide (83% Pt, 17.2 g; 0.0758 mmol). The
final purification by column chromatography (silica gel, THF/n-
hexane, 1:9) followed by recrystallization from chloroform/meth-
anol gave the bis[3]catenane 8e as a colorless, crystalline powder;
yield 85.7 mg, 60%. Mp >340 ꢀC (decomposition); 1H NMR (C6D6):
10.05 (s, 2H, NH), 10.04 (s, 2H, NH), 10.03 (s, 2H, NH), 9.94 (s, 2H,
NH), 8.49 (s, 2H, ArH), 8.42 (d, 2H, J¼8.3 Hz, ArH), 8.20 (s, 2H, ArH),
8.17 (d, 2H, J¼2.2 Hz, ArH), 8.11 (d, 2H, J¼2.5 Hz, ArH), 8.10 (s, 2H,
ArH), 8.06 (d, 2H, J¼2.2 Hz, ArH), 7.96 (d, 2H, J¼2.5 Hz, ArH), 7.58 (s,
2H, ArH), 7.50 (s, 2H, NH), 7.42–7.36 (m, 4H, ArH), 7.27 (s, 2H, ArH),
7.20–7.00 (m under the solvent peak, 8H, ArH, NH), 6.78 (s, 2H, NH),
6.72 (s, 2H, NH), 6.66 (dd, 2H, J¼8.0, 1.9 Hz, ArH), 6.58 (s, 2H, ArH),
6.55–6.50 (m, 4H, ArH), 6.33 (d, 2H, J¼2.2 Hz, ArH), 6.23 (d, 2H,
J¼1.9 Hz, ArH), 6.05 (d, 2H, J¼2.2 Hz, ArH), 6.02 (d, 2H, J¼2.2 Hz,
ArH), 4.58–4.46 (m, 8H, ArCH2Ar), 4.28–4.16 (m, 8H, OCH2),
Approach B: prepared from bisloop compound 7c (70.0 mg,
0.0413 mmol), octaalkenyl tetraurea 4c (88.5 mg, 0.0393 mmol) in
dichloromethane
(160 mL),
Grubbs’
catalyst
(12.9 mg,
0.0157 mmol), and triethylamine (1 mL). Hydrogenation in THF
(20 mL) using platinum dioxide (83% Pt, 16.1 mg; 0.0707 mmol).
The final purification by column chromatography (silica gel, THF/n-
hexane, 1:20) followed by recrystallization from chloroform/
methanol gave the bis[3]catenane 8c as a colorless, crystalline
powder; yield 72.4 mg, 48%. Mp >300 ꢀC (decomposition); 1H NMR
(C6D6): 9.99 (s, 2H, NH), 9.94 (s, 2H, NH), 9.91 (s, 2H, NH), 9.87 (s,
2H, NH), 8.30–8.19 (m, 8H, ArH), 8.07 (s, 2H, ArH), 8.00 (m, 4H, ArH),

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O. Molokanova et al. / Tetrahedron 65 (2009) 7220–7233
4.07–3.59 (m, 32H, OCH2), 3.31 (d, 2H, J¼12.1 Hz, ArCH2Ar), 3.22 (d,
2H, J¼11.1 Hz, ArCH2Ar), 3.19 (d, 2H, J¼11.4 Hz, ArCH2Ar), 3.15 (d,
2H, J¼11.8 Hz, ArCH2Ar), 2.13–2.85 (m, 24H, CH2), 1.65 (m, 4H, CH2),
1.58–0.89 (m, 128H, CH2, CH3); MS (ESI) m/z: calcd for
C204H268N16O28 (MHþþNaþþ2CH3CN) 1749.2, observed 1749.0.
(0.5 mL) were reacted as described for 9b. The residue formed after
evaporation of the reaction mixture was passed through a column
(silica gel, THF/n-hexane, 1:14). The crude product was dissolved in
THF (20 mL), platinum dioxide (83% Pt, 30.2 mg, 0.0133 mmol) was
added to the solution, and the reaction mixture was stirred vigor-
ously under a hydrogen atmosphere for 6 h at room temperature.
The final purification by column chromatography (silica gel, THF/n-
hexane, 1:14) followed by recrystallization from chloroform/n-
hexane gave the [8]catenane 9c as a colorless, crystalline powder;
yield 14.7 mg, 40%. Mp 120 ꢀC; 1H NMR (CD2Cl2): 9.38 (s, 8H, NH),
7.76 (s, 8H, ArH), 7.50 (s, 8H, ArH), 6.90 (s, 8H, NH), 6.41 (br s, 8H,
ArH), 6.13 (s, 8H, ArH), 5.75 (s, 8H, ArH), 4.27 (d, 8H, J¼11.7 Hz,
ArCH2Ar), 4.05–3.63 (m, 48H, OCH2), 2.94 (d, 8H, J¼11.7 Hz,
ArCH2Ar), 1.97 (m, 16H, CH2), 1.74 (m, 16H, CH2), 1.63 (m, 16H, CH2),
1.50–1.00 (m, 288H, CH2), 0.97 (t, 24H, J¼7.2 Hz, CH3); MS (ESI) m/z:
calcd for C312H480N16O32 (MþTHFþ2Naþ) 2542.8, observed 2542.4.
4.6. Synthesis of [8]catenanes 9
4.6.1. [8]Catenane 9a
A solution of tetraloop compound 5b (50.0 mg, 0.0260 mmol)
and tetraurea 4b (50.2 mg, 0.0248 mmol) in freshly distilled and
degassed dichloromethane (100 mL) was stirred at room temper-
ature for 96 h and for 20 h under reflux. Tetrahydrofuran (10 mL)
was added to the mixture, which was stirred under reflux for 18
days. The mixture was purged with nitrogen for 30 min and Grubbs’
catalyst (8.1 mg, 0.00992 mmol) was added. After 48 h of stirring,
the solvent was evaporated from under reduced pressure. The
residue was dissolved in chloroform (5 mL), and passed through
a column (silica gel, THF/n-hexane, 1:12). The crude product was
dissolved in THF (20 mL), platinum dioxide (83% Pt, 5.1 mg,
0.0223 mmol) was added to the solution, and the reaction mixture
was stirred vigorously under a hydrogen atmosphere for 6 h at
room temperature. The final purification by column chromatogra-
phy (silica gel, THF/n-hexane, 1:10) followed by recrystallization
from chloroform/n-hexane furnished (in addition to 11 mg of the
unreacted tetraloop 5b) the [8]catenane 9a as colorless, crystalline
powder; yield 32.5 mg, 32%. Mp >230 ꢀC (decomposition); 1H NMR
(CD2Cl2): 9.42 (s, 8H, NH), 7.74 (s, 8H, ArH), 7.72 (s, 8H, ArH), 6.91 (s,
8H, NH), 6.39 (s, 8H, ArH), 6.13 (s, 8H, ArH), 5.68 (s, 8H, ArH), 4.28 (d,
8H, J¼11.9 Hz, ArCH2Ar), 4.14–3.97 (m, 16H, OCH2), 3.97–3.84 (m,
16H, OCH2), 3.73 (t, 16H, J¼8.0 Hz, OCH2), 2.86 (d, 8H, J¼11.6 Hz,
ArCH2Ar),1.97 (m, 16H, CH2), 1.78 (m,16H, CH2), 1.50–1.00 (m, 144H,
CH2), 0.96 (t, 24H, J¼7.3 Hz, CH3); MS (ESI) m/z: calcd for
C232H320N16O32 (MþTHFþ2Naþ) 1981.7, observed 1981.2.
4.7. X-ray crystallography
X-ray diffraction measurements were performed on a Stoe-
IPDS-II diffractometer. An absorption correction was carried out
with the MULABS43 option in PLATON.44 Crystal data and re-
finement details are given in Table 3. The structures were solved by
SHELXD45 and refined by full-matrix least-squares techniques us-
ing SHELXL.45 The methylene chain C atoms were only refined
isotropically. All hydrogen atoms were inserted in calculated posi-
tions and refined using a riding model. Restraints had to be applied
to keep the geometric parameters in a reasonable range.
Acknowledgements
We thank the Deutsche Forschungsgemeinschaft for financial
support (grants Bo 523/14 and SFB 625).
4.6.2. [8]Catenane 9b
References and notes
A solution of tetraloop compound 5c (50.0 mg, 0.0233 mmol)
and tetraurea 4c (49.9 mg, 0.0222 mmol) in freshly distilled and
degassed dichloromethane (90 mL) was stirred at room tempera-
ture for 48 h; the complete formation of the heterodimer was
verified by 1H NMR. After the signals of the homodimer had dis-
appeared, the mixture was purged with nitrogen for 30 min and
Grubbs’ catalyst (70 mg, 0.0088 mmol) was added. After 48 h of
stirring, triethylamine (0.5 mL) was added and the solution was
stirred for 1 h and evaporated. The residue was dissolved in
dichloromethane (5 mL) and passed through a column (silica gel,
THF/n-hexane, 1:12). The crude product was dissolved in THF
(20 mL), platinum dioxide (83% Pt, 0.009 g; 0.0399 mmol) was
added to the solution, and the reaction mixture was stirred vigor-
ously under a hydrogen atmosphere for 6 h at room temperature.
The final purification by column chromatography (silica gel,
THF/hexane, 1:12) followed by recrystallization from chloroform/
n-hexane gave the [8]catenane 9b as a colorless, crystalline
powder; yield 39.4 mg, 41%. Mp >285 ꢀC (decomposition); 1H NMR
(CD2Cl2): 9.45 (s, 8H, NH), 7.74 (s, 8H, ArH), 7.64 (s, 8H, ArH), 6.68
(br s, 16H, ArH, NH), 6.13 (s, 8H, ArH), 5.89 (s, 8H, ArH), 4.28
(d, 8H, J¼11.7 Hz, ArCH2Ar), 4.06–3.63 (m, 48H, OCH2), 2.88 (d,
8H, J¼11.7 Hz, ArCH2Ar), 1.96 (m, 16H, CH2), 1.74 (m, 16H, CH2),
1.70–1.00 (m, 208H, CH2), 0.95 (t, 24H, J¼7.2 Hz, CH3); MS (ESI)
m/z: calcd for C264H384N16O32 (MþTHFþ2Naþ) 2206.8, observed
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