Influence of laterally attached alkyl groups on the conformational behaviour of a basic calix[4]arene: Combined NMR, molecular mechanics and X-ray study

Article abstract of DOI:10.1080/10610270903437044

Three new calixarenes 3-5 featuring an alkyl residue of different chain lengths attached to one of the central ring methylene groups of the basic calix[4]arene 1 have been prepared. A systematic study that includes also the lower homologous compound 2 showing the effect of the alkyl substitution on the conformational behaviour of the calixarene framework in comparison with the unsubstituted parent compound 1 is reported. The application of special 2D NMR techniques, 2D-EXSY and ROESY methods at various temperatures establishes that calixarenes 2-5 adopt the partial cone conformation of lower symmetry and far less the symmetric cone and 1,2-alternate conformations. In solution, they undergo a fast interconversion with relatively low activation energies of about 15 kcal/mol at room temperature. The conformer distribution is well reproduced by molecular mechanistic calculations (MMFF94), indicating the present conformers to assume the lowest steric energies. A single-crystal X-ray structure of the lateral ethyl derivative 2 corroborates these results, showing the molecule in a sterically favourable partial cone conformation.

Full text of DOI:10.1080/10610270903437044

This article was downloaded by: [Moskow State Univ Bibliote]
On: 08 October 2013, At: 06:45
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Supramolecular Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gsch20
Influence of laterally attached alkyl groups on the
conformational behaviour of a basic calix[4]arene:
combined NMR, molecular mechanics and X-ray study
Margit Gruner a , Conrad Fischer b , Tobias Gruber b & Edwin Weber b
a Institut für Organische Chemie , Technische Universität Dresden , Mommsenstr. 13,
D-01062, Dresden, Germany
b Institut für Organische Chemie , Technische Universität Bergakademie Freiberg , Leipziger
Str. 29, D-09596, Freiberg/Sachs, Germany
Published online: 17 Feb 2010.
To cite this article: Margit Gruner , Conrad Fischer , Tobias Gruber & Edwin Weber (2010) Influence of laterally attached
alkyl groups on the conformational behaviour of a basic calix[4]arene: combined NMR, molecular mechanics and X-ray study,
Supramolecular Chemistry, 22:4, 256-266, DOI: 10.1080/10610270903437044
To link to this article: http://dx.doi.org/10.1080/10610270903437044
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

Supramolecular Chemistry
Vol. 22, No. 4, April 2010, 256–266
Influence of laterally attached alkyl groups on the conformational behaviour of a basic
calix[4]arene: combined NMR, molecular mechanics and X-ray study
Margit Grunera, Conrad Fischerb, Tobias Gruberb and Edwin Weberb*
a
b
Institut fur Organische Chemie, Technische Universitat Dresden, Mommsenstr. 13, D-01062 Dresden, Germany; Institut fur
¨
Organische Chemie, Technische Universitat Bergakademie Freiberg, Leipziger Str. 29, D-09596 Freiberg/Sachs, Germany
¨
¨
¨
(Received 26 January 2009; final version received 23 October 2009)
Three new calixarenes 3–5 featuring an alkyl residue of different chain lengths attached to one of the central ring methylene
groups of the basic calix[4]arene 1 have been prepared. A systematic study that includes also the lower homologous
compound 2 showing the effect of the alkyl substitution on the conformational behaviour of the calixarene framework
in comparison with the unsubstituted parent compound 1 is reported. The application of special 2D NMR techniques,
2D-EXSY and ROESY methods at various temperatures establishes that calixarenes 2–5 adopt the partial cone
conformation of lower symmetry and far less the symmetric cone and 1,2-alternate conformations. In solution, they undergo
a fast interconversion with relatively low activation energies of about 15 kcal/mol at room temperature. The conformer
distribution is well reproduced by molecular mechanistic calculations (MMFF94), indicating the present conformers to
assume the lowest steric energies. A single-crystal X-ray structure of the lateral ethyl derivative 2 corroborates these results,
showing the molecule in a sterically favourable partial cone conformation.
Keywords: calixarenes; lateral substitution; synthesis; conformational study; solution 2D NMR measurements; X-ray
crystal structure
Introduction
only fragmentarily in a few cases of modified tetra-
hydroxycalix[4]- and -calix[5]arenes (7c,d). This warrants
dealing with the conformational property of laterally
monosubstituted calixarenes more broadly. Hence, a series
of calixarenes that feature a lateral substitution of alkyl
groups of different chain lengths and include a well-known
parent compound were considered for this purpose.
The concrete system of compounds, which was chosen
for this study, as specified in Figure 1, covers the tetra-tert-
butyltetramethoxycalix[4]arene (1) as the reference and
2–5 as the test compounds. This shows an advantage since
the conformational behaviour of 1 is known rather detailed
from previous work (10). Moreover, for the synthesis of
2–5, one can follow a literature method elaborated for
calixarene 2 by Scully et al. (7a). The conformational
properties of 2–5, which are described here, were
determined from a detailed solution NMR study. This
involves measurements at various temperatures and uses
special 2D NMR techniques to yield a full description of
the conformer distribution and the free activation energies
of conformational interconversion. We also report on the
crystal structure of the corresponding laterally ethyl-
monosubstituted calixarene 2, being the first crystal
structure of a laterally monosubstituted tetramethoxy-
calix[4]arene.
Calixarenes and their derivatives are an important class of
compounds that have been extensively investigated
regarding their supramolecular recognition properties
during the past two decades (1). Calixarenes have also
emerged as very attractive building blocks for the
development of highly ingenious functional systems and
devices (2). In both of these respects, much work has been
dedicated to the synthesis of calixarenes modified on the
upper and lower rims, giving rise to an enormous variety of
compound structures (3). Homocalixarenes (4), thiacalix-
arenes (5) and others (1), where the bridging methylene
units of the conventional calixarene framework are
completely replaced by modifying organic groups or
hetero-atoms, represent further currently studied yet rather
well-known types of structural modifications of the
calixarene family (6). By way of contrast, calixarenes
featuring a substitution of only one of the methylene
bridges are presently rare (7), although these laterally
substituted calixarenes may open interesting aspects of
calixarene chemistry including linked constructions of
oligotopic receptors (8), as well as systems distinguished
by particular anchoring of the calixarene to a specific
target or support (2, 9). As a result, the conformational
behaviour of this particular compound type is also studied
*Corresponding author. Email: edwin.weber@chemie.tu-freiberg.de
ISSN 1061-0278 print/ISSN 1029-0478 online
q 2010 Taylor & Francis
DOI: 10.1080/10610270903437044
http://www.informaworld.com

Supramolecular Chemistry
257
less important for a designed purpose (15). As a rule, these
conformations are mainly determined by the ring size or the
nature and the space required for the substituents being
present at the upper and lower rims of the calixarene
molecule. Conformational property will also depend on the
physical condition, including the type of the solvent as well
as the presence of a proper guest molecule. However, in no
manner, O-alkylated calixarenes that feature an alkyl residue
laterally attached to one of the methylene groups of the
central ring have been studied conformationally. Only
analogous tetrahydroxycalixarenes were taken for a
corresponding study (7c,d).
A well-known molecular structure is that of the tetra-
tert-butyltetramethoxycalix[4]arene (1), which was
chosen as the parent compound for the test. According to
the NMR data (10), 1 in a solution of CDCl3 exists in
equilibrium of all four conventional conformers of which
the partial cone conformation is the preferred one.
A partial cone conformer is also reported for the solvent-
free calixarene 1 (16) as well as for the furan (17) and
dichloromethane (18) inclusion compounds in the solid
state, while a corresponding sodium complex shows a cone
conformation both in the crystal structure and in
CDCl3/CD3CN solution due to the coordination of the
sodium ion (10b). Thus, it is clear that a potential change
of the conformational behaviour in the present cases of
calixarenes, in comparison with 1, is attributed to the
laterally substituted alkyl groups.
Figure 1. Compounds studied in this paper.
Results and discussion
Synthesis
Calixarene 1, which is the basic compound for the synthesis
of 2–5, was obtained from a two-stage methylation reaction
of 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrahydroxy-
calix[4]arene (11) using in a starting phase-transfer process
sodium hydroxide, dimethyl sulphate and tetrabutylam-
monium bromide to yield the intermediate compound with
two distal methyl groups, followed by treatment with
sodium hydride and iodomethane in a final methylation step
(12). A corresponding one-step methylation method of the
parent tetrahydroxycalixarene with sodium hydride and
iodomethane, described in the literature (10a, 13), did not
prove competitive in its result. The target calixarenes 2–5
featuring different laterally substituted alkyl groups were
prepared by deprotonation of 1 with n-butyllithium and
reaction with respective alkyl halides following the
procedure described by Scully et al. (7a).
A complex pattern of signals in the NMR spectra of the
alkyl-substituted calixarenes 2–5 in both CDCl3 and
tetrachloroethane-d2 (TCl-d2) at various temperatures
indicates that the compounds exist in different conformers,
as demonstrated exemplary for the lateral propyl derivative 3
in Figure 2. To minimise the signal broadening and to
separate the overlapping region of methine and methylene
signals, we carried out the NMR experiments at an optimised
temperature of 269 K, yielding three different signals for the
methine protons between 4.47 and 4.79ppm in CDCl3 for
compounds 2–5. Detailed 2D NMR measurements using
COSY-, 1H/13C-correlated HSQC (19), HMBC (20) as well
as NOESY and ROESY experiments gave a full determi-
1
nation of conformers (specified in Figure 3; H and 13C
chemical shifts are summarised in Tables S1–S4 of the
Supplementary Material). A special denotation of the
calixarene scaffold in the three observed conformations is
illustrated in Figure 3, indicating similarities in the chemical
shift for different pairs of atoms.
Conformational study
Conformational predominance and conformational flexi-
bility are important structural parameters of a calixarene
molecule, being decisive of its supramolecular behaviour
both in solution and solid state (1–3). While the so-called
cone conformation, providing a spacious cavity structure,
is perhaps the most frequent conformation of the
existing calixarenes (1, 14), the other types of molecular
conformations, including partialcone, 1,2-and1,3-alternate
conformations, are somewhat more rarely found though not
Depending on the alignment of the four arene units with
reference to the lateral substituent, there are 16 different
conformational isomers possible (Figure 4). Six of them are
mirror images of each other resulting in identical NMR
spectra. The 2D experiments show that the laterally
substituted n-alkyl calixarenes, studied here, exist mainly
in one partial cone conformation ( pacoD in Figure 4), with
an equatorial substituent between two syn-orientated arene

258
M. Gruner et al.
Figure 2. 1H NMR spectra of 3 in CDCl3 at T ¼ 269 and 295 K.
Figure 3. Denotation of atoms of the conformers of 2–5 studied in this paper.
units, and also as 1,2-alternate (alt2C in Figure 4) and cone
(coneB in Figure 4) conformers (Scheme 1), which are
revealed in the region of the OCH3 groups of the HSQC
spectrum (Figure 5). In the ROESY spectrum (Figure 6), all
conformers possess stronger positive cross-peaks between
the axial methine H-1 protons in the bridge and the near
H-8 protons of the methoxy groups than between these
protons and the H-3 protons of the same aromatic rings,
indicating the vicinity of one of the methoxy groups on the
lower rim to H-1. Further characteristic-specific inter-
actions between aromatic protons of the calixarene and
protons of OCH3 or tert-butyl groups neighbouring the
methylene bridge are marked in Figure 6. These
correlations suggest the orientation of arene units of the
calixarene ring for each individual isomer. For example, the
paco isomer is characterised by the cross-peaks 8O0/11O0,
16O/13O, 16O0/5O0 and 16O0/13O, and the 1,2-alternate
species by the 8B/11B and 8B/13B relation.
Furthermore, in Figure 6, negative cross-peaks between
different H-1 proton signals can be observed due to
chemical exchange processes in the form of a dynamic
interconversion of conformers. To extract the rate constants
for the conformational chemical exchange (kchem), the 2D-
EXSY method (21) was used, and thus the free activation
energies DG # of the interconversion have been calculated
(Table 1). Interestingly, compounds 2–5 display a fast

Supramolecular Chemistry
259
Figure 4. Possible conformers of 2 with sterical energy differences (in kcal/mol) relative to the most stable partial cone (pacoD)
conformation. The filled and unfilled circles represent an ‘up’ or ‘down’ orientation of the methoxy groups, respectively. Mirror images
are separated by a broken line and indicated by inverted letters.
Scheme 1. Conformational isomers and conformational behaviour in solution of the laterally alkyl-substituted calixarenes 2–5 (R as
specified in Figure 1).

260
M. Gruner et al.
Figure 5. HSQC spectrum of 3 in CDCl3 at 265 K (region of OCH3 only).
Figure 6. Part of the ROESY spectrum of 3 in CDCl3 at 265 K.

Supramolecular Chemistry
261
partial cone/cone interconversion involving values of free
activation energy rather comparable to the reported
,13 kcal/mol for the laterally unsubstituted prototype
calixarene 1 in the same solvent (10a). The observed
influence of the solvent and the temperature on the
conformational behaviour is in agreement with the
common expectation. In this connection, the conformation-
al reorientation was found to be faster at higher temperature
and retarded in solution of the larger and less polar solvent
molecules of TCl-d2 compared to CDCl3.
The conformer distribution of 1–5, summarised in
Table 2, shows that the partial cone conformation
predominates the present series of tetra-tert-butyltetra-
methoxycalix[4]arenes in CDCl3, varying only little by
introduction of the lateral alkyl substituents, i.e. the
predominance of the partial cone conformation is only
slightly affected. Nevertheless, its frequency decreases to
some extent for the benefit of the rarely occurring cone and
1,2-alternate structures in the following manner. With
increasing chain length, the ratio of the partial cone
conformation remains nearly unchanged, while the cone
conformation decreases and the 1,2-alternate confor-
mation increases. However, as contrasted with the
prototype calixarene 1, for none of the studied compounds
a 1,3-alternate conformation was detected. This points to a
predominance of thermodynamically stable conformers
and suggests the avoidance of an isoclinal arrangement of
the lateral substituent, presumably for energetic reasons.
MM calculation
To evaluate the steric influence of the lateral alkyl
substituent, relative energies of the different conformers of
2 as a model compound, summarised in Figure 4, were
determined using the MMFF94 force field (22) as
implemented in the SYBYL software. As proven by
previous mechanistic studies (7d), all conformations with
an axial arrangement of the lateral substituent are
energetically discriminated due to their higher angle
bending energy. The predominance of the partial cone
conformation resulting from the NMR experiments,
bearing the lateral substituent in an equatorial position
between syn-orientated arene units in solution ( pacoD),
may thus be explained with the avoidance of repulsion
between the a-C-atom of the lateral alkyl moiety and the
neighbouring methoxy groups, indicated by their low
sterical energies (Table 3). Analogously, the frequency and
stability of the coneB conformer detected by NMR can be
assumed due to its similar low ground state energy. It is
also shown that the energy gap between the 1,2-alternate
(alt2C) and the 1,3-alternate conformer is small, giving
evidence of their potential presence in solution. The fact
that only the 1,2-alternate conformer is detected in the
NMR could result from its higher energy gap to the lowest
energy partial cone conformer (,3.8 kcal/mol for alt2C)

262
M. Gruner et al.
Table 3. Relative energies (in kcal/mol) for possible
conformers of ethyl compound 2 obtained by the MMFF94 force
field (SYBYL) and calculated populations.
Relative energy Relative to pacoD Population
(kcal/mol)
Conformation
(kcal/mol)
(%)
coneA
coneB
pacoA
pacoB
pacoC
pacoD
alt2A
alt2B
alt2C
alt3
225.76
233.15
233.99
227.77
227.58
225.75
237.02
233.00
229.50
227.98
0.01
7.40
8.24
2.02
1.83
0.00
11.27
7.25
3.75
2.23
47.13
–
–
1.58
2.18
47.93
–
–
0.08
1.11
leading to separate signals, whereas the interconversion to
the 1,3-alternate conformer is too fast on the NMR time
scale.
Crystal structure of compound 2·CHCl3
In order to compare the conformational results from the
solution NMR study with the conformational behaviour in
the solid state, we tried to obtain suitable crystals of
compounds 2–5 for the X-ray study. Unfortunately, we
were unsuccessful in obtaining high-quality crystals in the
case of 3–5, presumably due to the high flexibility of the
rather extended alkyl chains. However, the corresponding
laterally ethyl-substituted compound 2 yielded colourless
crystals (space group Pca21) from a solvent mixture of
methanol and chloroform (2:1) suitable for the X-ray study
(Table 4). The crystals were analysed to be a stoichiometric
1:1 solvate with chloroform. Not surprisingly, also in the
solid state, one low-energy partial cone conformer bearing
the lateral substituent in an equatorial position between
syn-orientated arene units is found (Figure 7). This result is
in agreement both with the predominance of the partial
cone conformation in solution and with the lowest energy
conformer ( pacoD) from the MM calculation.
Selected conformational parameters of the calixarene
molecule 2 are summarised in Table S5. The opposite
phenyl rings A and C differ only little from coplanarity
[8.98 (1)], while the aromatic rings B and D are orientated
in an angle of 42.88 (1). Similar to a comparable 2:1 solvate
of the lateral unsubstituted calixarene 1 with dichloro-
methane (18), the methoxy group of ring D points outwards
and maintains no interactions with the other rings. In
consequence of the compact structure caused by the partial
cone conformer, the calixarene does not allow a cavitate
inclusion of solvent molecules, which are therefore located
interstitially in the crystal lattice. With reference to the
crystal packing, the calixarene molecules are orientated
translatory staggered along the crystallographic b-axis
(Figure 8). Corresponding to the non-polar character of the
calixarene, the interactions are limited to weak C–H· · ·p

Supramolecular Chemistry
263
conformational property of the tetramethoxycalix[4]arene
system.
Table 4. Crystal data and selected details of the data collection
and refinement calculations of compound 2·CHCl3.
The following main conclusions can be obtained from
this study. (1) The lateral attachment of an alkyl residue to
one of the central ring methylene groups of the basic
calixarene 1 has no substantial consequence on the
conformational behaviour. That is, independent of the
chain length, a respective substitution of an alkyl group
does not hamper the predominance of the partial cone
conformation of 1 in chloroform solution, as proven by
NMR spectroscopy. This particular conformation was also
found to be low energetic in the calculated sterical energies.
Moreover, the crystal structure of compound 2 in its
solvated form with chloroform is in structural agreement,
showing the partial cone conformation in the crystalline
state. (2) As against the unsubstituted calixarene 1, the free
activation energy for the conformational interconversion of
2–5 in solution is found to be only moderately higher.
Hence, it is shown that (3) an alkyl substitution of one of the
hydrogen atoms of a methylene group between the flanking
aryl residues of the central ring offers a very promising
possibility for the coupling of a basic tetramethoxy-
calix[4]arene structural element to spacer or linker units in
order to realise future developments of new complex
framework structures without substantial impairment of the
initial calixarene conformation, while corresponding
modifications at the upper and lower rim sites normally
result in distinct changes of the conformational behaviour.
Future work is required to explore the effect of more
than one laterally attached alkyl group or of a substituent
containing polar or functional units in the side chain.
Investigations in this direction are the aim of our group.
Compound
2·CHCl3
Empirical formula
Formula weight (g/mol)
Crystal system
C51H69Cl3O4
852.4
Orthorhombic
Pca21
23.9269(5)
16.8437(4)
12.6634(3)
90.00
Space group
˚
a (A)
˚
b (A)
˚
c (A)
a (8)
b (8)
g (8)
90.00
90.00
3
˚
V (A )
5103.6(2)
4
1832
Z
F (000)
Dc (mg m23
)
1.109
0.219
m (mm21
Data collection
Temperature (K)
)
93(2)
57,108
1.21–28.10
231/31, 222/21,
216/10
No. of collected reflections
Within the u limit (8)
Index ranges ^h, ^k, ^l
No. of unique reflections
Rint
Refinement calculations: full-matrix
least squares on all F 2 values
Weighting expression, wa
9944
0.0968
[s2(F2o) þ (0.1788P)2
þ 4.6405P ]21
537
8817
No. of refined parameters
No. of F values used [I . 2s(I)]
Final R indices
R (¼SjDFj/SjFoj)
0.0843
0.2405
1.092
wR on F 2
S (¼Goodness of fit on F 2)
23
˚
Final Drmax/Drmin (e A
)
0.000
a P ¼ (F2o þ 2F2c).
Experimental
contacts (23) involving guest and calixarene molecules
˚
Materials
[d(C1GA· · ·centroid C) ¼ 3.569 (1) A] or the calixarene
molecules among each other [d(C33· · ·centroid B) ¼ 3.486
1-Iodopropane (Fluka, Buchs, Switzerland), 1-iodopen-
tane (Acros, Morris Pla, NJ, USA) and 1-bromodecane
(Fluka) were used as received. The n-BuLi (1.6 M in
hexane) was purchased from Acros. Analytical TLC was
performed on precoated silica gel plates (60 F254; Merck,
Darmstadt, Germany). Organic solvents were purified by
standard procedures (24).
˚
(1) A], as specified in Table S6.
Conclusions
According to the literature (1, 7), calixarenes showing a
substitution of a single methylene bridge, especially in the
case of an alkyl substitution, are a rather low developed
class of compounds. As derivatives of the archetype
tetramethoxycalix[4]arene 1, only the first two members of
the potential compound series, i.e. the methyl and ethyl (2)
derivatives, have previously been synthesised and
preliminarily described regarding their conformational
behaviour. With the present calixarenes 3–5 featuring the
corresponding mode of lateral substitution but using
higher alkyl groups of different chain lengths, new
examples of this particular compound type have now been
made available. They enable to perform a first systematic
study of the influence of the given alkyl groups on the
Techniques
Melting points were determined with a hot-stage
microscope (VEB Dresden Analytik, Dresden, Germany)
and are uncorrected. 1H and 13C NMR spectra were
recorded using a Bruker DRX 500 spectrometer.
The chemical shifts (d) are reported in ppm relative to
TMS ¼ 0 ppm. Mass spectra were recorded with EI-MS
(Finnigan MAT 8200). The elemental analyses were
performed with a Heraeus CHN rapid analyser.

264
M. Gruner et al.
(1:1) yielded 60% of intermediate 5,11,17,23-tetra-tert-
butyl-26,28-dihydroxy-25,27-dimethoxycalix[4]arene as
a colourless solid, mp 235–2388C. Following the
literature protocol (13), this compound was caused to
react with NaH and iodomethane to afford 67% of
calixarene 1 as a colourless solid, mp 242–2448C (lit.
(12) 242–2438C).
General procedure for the synthesis of the laterally
monoalkylated calix[4]arenes (2–5)
The synthesis of products 2–5 follows the protocol
described by Scully et al. (7a). To a stirred solution of
1 (1.0 mmol) in dry THF (30 ml), n-BuLi (1.6 N in
n-hexane, 2.9 ml, 4.6 mmol) was added at room
temperature under argon. After having stirred for
30 min, the respective 1-halogenalkane (8.0 mmol) was
added via a syringe to the solution, causing a change of
its colour from red to yellow. Stirring was continued for
1 h. The solvent was removed under reduced pressure
and the residue partitioned into water–dichloromethane
(1:1, 60 ml). The organic layer was washed with water
(2£ 30 ml), dried (MgSO4) and evaporated under
reduced pressure. Recrystallisation from MeOH yielded
the products as colourless solids. Experimental, MS and
elemental analysis data of the individual compounds are
specified below. For the detailed 2D NMR experiments,
all substances were dried for 24 h under vacuum at 508C.
The respective NMR data of 2–5 are given in the
Supplementary Material (Tables S1–S4). The NMR data
for 2 correspond to the literature (7a).
Figure 7. Molecular structure of the solvate compound 2· CHCl3 .
5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetramethoxy-2-
ethylcalix[4]arene (2)
1-Bromoethane was used. Yield 0.42 g (57%), mp
183–1858C [lit. (7a) 184–1868C].
5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetramethoxy-2-
n-propylcalix[4]arene (3)
1-Iodopropane was used. Yield 0.34 g (46%), mp
132–1358C. Anal. Calcd for C51H70O4 0.5 MeOH:
C 81.06, H 9.51. Found: C 80.99, H 9.78%. MS (70 eV),
m/z (%): 747 (Mþ, 100), 748 (52), 358 (35), 177 (28).
Figure 8. Packing diagram of 2· CHCl3 viewed down the b-axis,
illustrating the strands of calixarene molecules and localisation of
the solvent molecules.
Synthesis of 5,11,17,23-tetra-tert-butyl-25,26,27,28-
tetramethoxycalix[4]arene (1)
5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetramethoxy-2-
n-pentylcalix[4]arene (4)
A mixture of 5,11,17,23-tetra-tert-butyl-25,26,27,28-
tetrahydroxycalix[4]arene (11), NaOH (aqueous, 50
p.c.), dimethyl sulphate and tetrabutylammonium bro-
mide in toluene was reacted following a known
procedure (12). Recrystallisation from MeOH–CHCl3
1-Iodopentane was used. Yield 0.35 g (47%), mp
76–808C. Anal. Calcd for C53H74O4: C 82.12, H 9.62.
Found: C 82.15, H 9.80%. MS (70 eV), m/z (%): 775 (Mþ,
100), 776 (64), 372 (43), 177 (14).

Supramolecular Chemistry
265
(6) For recent studies, see: (a) Columbus, I.; Biali, S.E. J. Org.
Chem. 2008, 73, 2598–2606. (b) Columbus, I.; Biali, S.E.
Org. Lett. 2007, 9, 2927–2929.
(7) (a) Scully, P.A.; Hamilton, T.M.; Bennett, J.L. Org. Lett.
2001, 3, 2741–2744. (b) Middel, O.; Greff, Z.; Taylor, N.J.;
Verboom, W.; Reinhoudt, D.N.; Snieckus, V. J. Org. Chem.
2000, 65, 667–675. (c) Bergamaschi, M.; Bigi, F.;
Lanfranchi, M.; Maggi, R.; Pastorio, A.; Pellinghelli,
M.A.; Peri, F.; Porta, C.; Satori, G. Tetrahedron 1997, 53,
5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetramethoxy-2-
n-decylcalix[4]arene (5)
1-Bromodecane was used. Yield 0.37 g (44%), mp
139–1448C. Anal. Calcd for C58H84O4 1.5 MeOH:
C 80.00, H 10.15. Found: C 79.85, H 9.88%. MS (70 eV),
m/z (%): 845 (Mþ, 100), 846 (63), 407 (42), 177 (32).
¨
13037–13052. (d) Biali, S.E.; Bohmer, V.; Cohen, S.;
X-ray crystallography
Ferguson, G.; Gru¨ttner, C.; Grynspan, F.; Paulus, E.F.;
Thondorf, I.; Voigt, W. J. Am. Chem. Soc. 1996, 118,
12938–12949.
Crystals of 2 suitable for X-ray diffraction analysis were
obtained by slow recrystallisation from methanol–chloro-
form (2:1) solution. The intensity data were collected on a
Bruker APEX II diffractometer with Mo Ka radiation
¨
(8) (a) Podoprygorina, G.; Janke, M.; Janshoff, A.; Bohmer, V.
Supramol. Chem. 2008, 20, 59–69. (b) Breitkreuz, C.J.;
Zadmard, R.; Schrader, T. Supramol. Chem. 2008, 20,
109–115. (c) Othman, A.B.; Lee, Y.H.; Ohto, K.; Abidi, R.;
Kim, Y.; Vicens, J. J. Incl. Phenom. Macrocycl. Chem.
2008, 62, 187–191. (d) Baklouti, L.; Cheriaa, N.;
Mahouachi, M.; Abidi, R.; Kim, J.S.; Kim, Y.; Vicens, J.
J. Incl. Phenom. Macrocycl. Chem. 2006, 54, 1–7.
(e) Garozzo, D.; Gattuso, G.; Notti, A.; Pappalardo, A.;
Pappalardo, S.; Parisi, M.F.; Perez, M.; Pisagatti, I. Angew.
Chem. 2005, 117, 4970–4974 (Angew. Chem. Int. Ed. 2005,
44, 4892–4896).
˚
(l ¼ 0.71073 A) using v- and f-scans. Reflections were
corrected for background and Lorentz polarisation effects.
Preliminary structure models were derived by application
of direct methods (25) and were refined by full-matrix
least-squares calculation based on F 2 for all reflections
(26). All hydrogen atoms were included in the models in
calculated positions and were refined as constrained to
bonding atoms. Relevant crystal data together with the
refinement details are listed in Table 4.
(9) (a) Costa, A.I.; Prata, J.V. Supramol. Chem. 2008, 20,
95–108. (b) Jain, V.K.; Pandya, R.A.; Pillai, S.G.;
Shrivastav, P.S. Talanta 2006, 70, 257–266. (c) Vocanson,
F.; Seigle-Ferrand, P.; Lamartine, R.; Fort, A.; Coleman,
A.W.; Shahgaldian, P.; Mugnier, J.; Zerroukki, A. J. Mater.
Sci. 2003, 13, 1596–1602.
(10) (a) Gutsche, C.D.; Dhawan, B.; Levine, J.A.; Kwang, H.N.;
Bauer, L. Tetrahedron 1983, 39, 409–426. (b) Blixt, J.;
Detellier, C. J. Am. Chem. Soc. 1995, 117, 8536–8540.
Crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic Data
Centre (No. CCDC 748215). Copies of this information
may be obtained free of charge from The Director, CCDC,
12 Union Road, Cambridge CB2 1EZ, UK. Fax (þ44)
1223-336-033; E-mail: deposit@ccdc.cam.ac.uk or www.
ccdc.cam.ac.uk.
´
(c) Harada, T.; Rudzinski, J.M.; Shinkai, S. J. Chem. Soc.,
Perkin Trans. 2 1992, 2109–2115. (d) Van Loon, J.-D.;
Groenen, L.C.; Wijmenga, S.S.; Verboom, W.; Reinhoud,
D.N. J. Am. Chem. Soc. 1991, 113, 2378–2384.
Supplementary Material
1H and 13C NMR data of 2–5 in CDCl3 and TCl-d2,
selected conformational parameters and geometric par-
ameters of potential hydrogen bond-type interactions from
the crystal structure of 2·CHCl3 are available as
Supplementary Material, available online.
(11) Gutsche, C.D.; Dhawan, B.; No, K.H.; Muthukrishnan, R.
J. Am. Chem. Soc. 1981, 103, 3782–3792.
´
ˆ
(12) Bitter, I.; Gru¨n, A.; Agai, B.; Toke, L. Tetrahedron 1995,
51, 7835–7840.
(13) (a) Iwamoto, K.; Araki, K.; Shinkai, S. J. Org. Chem. 1991,
56, 4955–4962. (b) Gutsche, C.D.; Dhawan, B.; Levine,
J.A.; No, K.H.; Bauer, L.J. Tetrahedron 1983, 39, 409–426.
¨
(14) Bohmer, V. Angew. Chem. 1995, 107, 785–818 (Angew.
Chem., Int. Ed. 1995, 34, 713–745).
Acknowledgements
(15) For example, see: O’Malley, S.; Alhashimy, N.; O’Mahony,
J.; Kieran, A.; Pryce, M.; Nolan, K. Tetrahedron Lett. 2007,
48, 681–684.
(16) Grootenhuis, P.D.; Kollman, P.A.; Groenen, L.C.; Rein-
houdt, D.N.; van Hummel, G.J.; Ugozzoli, F.; Andreetti,
G.D. J. Am. Chem. Soc. 1990, 112, 4165–4176.
(17) Fischer, C.; Gruber, T.; Seichter, W.; Weber, E. Acta Cryst.
2007, E63, o4572–o4573.
(18) Fischer, C.; Gruber, T.; Seichter, W.; Schindler, D.; Weber,
E. Acta Cryst. 2008, E64, o673.
(19) Bodenhausen, G.; Ruben, D.J. Chem. Phys. Lett. 1980, 69,
185–189.
(20) (a) Summer, M.F.; Marzilli, L.G.; Bax, A. J. Am. Chem.
Soc. 1986, 108, 4285–4294. (b) Bax, A.; Summer, M.F.
J. Am. Chem. Soc. 1986, 108, 2093–2094. (c) Bax, A.;
Aszalos, A.; Dinya, Z.; Sudo, K. J. Am. Chem. Soc. 1986,
108, 8056–8063.
This work was supported by the German Federal Ministry of
Economics and Technology (BMWi) under Grant No. 16IN0218
‘ChemoChips’. The authors are also grateful to Dr I. Thondorf for
help with the MM calculation.
References
(1) Gutsche, C.D. Calixarenes – An Introduction, 2nd ed.;
Royal Society of Chemistry: Cambridge, UK, 2008.
(2) Baklouti, L.; Vicens, J.; Harrowfield, J. Calixarenes in the
Nanoworld; Springer: Dordrecht, 2007.
¨
(3) Asfari, M.Z.; Bohmer, V.; Harrowfield, J.; Vicens, J.
Calixarenes 2001; Kluwer: Dordrecht, 2001.
¨
(4) Ibach, S.; Prautzsch, V.; Vogtle, F.; Chartroux, C.; Gloe, K.
Acc. Chem. Res. 1999, 32, 729–740.
(5) Morohashi, N.; Narumi, F.; Iki, N.; Hattori, T.; Miyano, S.
Chem. Rev. 2006, 106, 5291–5316.

266
M. Gruner et al.
(25) Sheldrick, G.M. SHELXL-97: Program for Crystal
(21) (a) Pons, M.; Millet, O. Progr. Nucl. Magn. Res. Spectr.
2001, 28, 267–324. (b) Perrin, C.L.; Dwyer, T. Chem. Rev.
1990, 90, 935–967.
¨
Structure Solution; University of Gottingen: Germany,
1990.
(22) Halgren, T.A. J. Comput. Chem. 1999, 20, 730–748.
(23) Nishio, M. CrystEngComm 2004, 6, 130–158.
(24) Smallwood, I.M. Handbook of Organic Solvent Properties;
Arnold: London, 1996.
(26) Sheldrick, G.M. SHELXL-97: Program for Crystal
¨
Structure Refinement; University of Gottingen: Germany,
1990.