Synthesis, aggregation, and adsorption phenomena of shape-persistent macrocycles with extraannular polyalkyl substituents

Article abstract of DOI:10.1021/ja003990x

The synthesis of shape-persistent macrocycles based on the phenyl-ethynyl backbone containing various extraannular alkyl side chains is described. Although compound solubility increases with increasing size of the side groups, decreasing the solvent polar

Full text of DOI:10.1021/ja003990x

J. Am. Chem. Soc. 2001, 123, 5651-5659
5651
Synthesis, Aggregation, and Adsorption Phenomena of
Shape-Persistent Macrocycles with Extraannular Polyalkyl
Substituents
Sigurd Ho1ger,*,§ Klaus Bonrad,§ Ahmed Mourran,*,‡ Uwe Beginn,‡ and Martin Mo1ller‡
Contribution from the Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz,
Germany, and Organische Chemie III/Makromolekulare Chemie, UniVersita¨t Ulm, D-89069 Ulm, Germany
ReceiVed NoVember 16, 2000
Abstract: The synthesis of shape-persistent macrocycles based on the phenyl-ethynyl backbone containing
various extraannular alkyl side chains is described. Although compound solubility increases with increasing
size of the side groups, decreasing the solvent polarity induces aggregation of the rings by nonspecific
interactions. This was investigated by proton NMR spectroscopy. The magnitude of aggregation can be varied
by using solvent mixtures of different hexane content, supporting the model of a solvophobic effect. From
1,2,4-trichlorobenzene solution the macrocycle 1c adsorbs at the surface of highly oriented pyrolitic graphite
(HOPG). The two-dimensional order of the structure was investigated by scanning tunneling microscopy (STM)
revealing the formation of a two-dimensional lattice of p12mm symmetry with lattice parameters A ) 3.6 nm,
B ) 5.7 nm, and Γ ) 74°.
Introduction
hydrogen bonds in cyclopeptides or cyclosaccharides lead to
large association constants and, even at low concentrations, lead
to the formation of extended structures.4 Weaker forces, like
π-π interactions, have been used to aggregate phenyl-ethynyl
or phenyl-butadienyl macrocycles.5 In these cases the occurrence
of aggregation strongly relies on the electronic structure of the
molecules; only macrocycles with electron-deficient core struc-
tures show the behavior of self-aggregation.6
During our work on the synthesis and the adaptable behavior
of shape-persistent macrocycles we also became interested in
the organization of these molecules into structures of higher
dimensionality.7 As we have shown in our previous work, the
synthesis of functionalized structures can be performed in good
to high yields by the oxidative coupling of rather rigid phenyl-
ethynyl oligomers containing ethynyl end groups.2b,8 Under-
standing how these molecules can be organized in a predictable
way will provide the basis for obtaining defined arrangements
of their functional groups in one or more dimensions.
One important objective in supramolecular chemistry is the
preparation of molecules which organize into well-defined
superstructures.1 The possibility to control the organization by
defined structure variations helps to understand the important
forces and geometrical requirements necessary for molecular
self-assembly. Moreover, these superstructures may act as
templates for the arrangement of substances whose organization
parameters are even more difficult to control, they may facilitate
epitaxial or topographic organization.
Macrocyclic compounds and their aggregation phenomena
have attained increasing attention over the past years.2 Based
on Chandrasekhar’s pioneering work on columnar mesophases
of discotic (disklike) molecules, rings with a defined internal
void (shape-persistent macrocycles) were examined as valuable
candidates for the formation of hollow columns.3 One could
envision that the arrangement of the molecules in an axial stack
would produce a molecular tube that, if functionalized appro-
priately, may give rise to ion channels, micro reaction chambers
or functionalized rodlike micellar aggregates.
(4) (a) Ghadiri, M. R.; Kobayashi, K.; Granja, J. R.; Chadha, R. K.;
McRee, D. E. Angew. Chem. 1995, 107, 76.; Angew. Chem., Int. Ed. Engl.
1995, 34, 3. (b) Clark, T. D.; Ghadiri, M. R. J. Am. Chem. Soc. 1995, 117,
12364. (c) Gattuso, G.; Menzer, S.; Nepogodiev, S. A.; Stoddart, J. F.;
Williams, D. J. Angew. Chem. 1997, 109, 1615; Angew. Chem., Int. Ed.
Engl. 1997, 36, 1451.
(5) (a) Zhang, J.; Moore, J. S. J. Am. Chem. Soc. 1992, 114, 9701. (b)
Shetty, A. S.; Zhang, J.; Moore, J. S. J. Am. Chem. Soc. 1996, 118, 1019.
(c) Tobe, Y.; Utsumi, N.; Kawabata, K.; Naemura, K. Tetrahedron Lett.
1996, 37, 9325. (d) Tobe, Y.; Utsumi, N.; Nagano, A.; Naemura, K. Angew.
Chem. 1998, 111, 1347; Angew. Chem., Int. Ed. Engl. 1998, 37, 1285. (e)
Tobe, Y.; Nagano, A.; Kawabata, K.; Sonoda, M.; Naemura, K. Org. Lett.
2000, 2, 3265.
The strength of the attractive forces between the single units
of the stack can vary over a broad range. For example, multiple
* Corresponding author. Fax: (+49) 6131-379 100. E-mail: hoeger@
mpip-mainz.mpg.de.
§ Max Planck Institute for Polymer Research.
‡ University of Ulm.
(1) (a) Lehn, J.-M. Supramolecular Chemistry; VCH: Weinheim, 1995.
(b) Schneider, H.-J.; Yatsimirsky, A. Principles and Methods in Supramo-
lecular Chemistry, VCH: Weinheim, 2000. (c) Fuhrhop, J.-H.; Ko¨ning, J.
Membranes and Molecular Assemblies: The Synkinetic Approach; The
Royal Society of Chemistry: Cambridge, 1994.
(2) Reviews about shape-persistent macrocycles: (a) Moore, J. S. Acc.
Chem. Res. 1997, 30, 402. (b) Ho¨ger, S. J. Polym. Sci., Part A: Polym.
Chem. 1999, 37, 2685. (c) Haley, M. M.; Pak, J. J.; Brand, S. C. Top. Curr.
Chem. 1999, 201, 81.
(6) Independently, the solvophobic π-stacking of phenylene ethynylene
macrocycles and oligomers has been reported by others: (a) Tanikawa, S.;
Moore, J. S. Polym. Prepr. (Am. Chem. Soc., DiV. Polym. Chem.) 1999, 40
(2), 169. (b) Lahiri, S.; Thompson, J. L.; Moore, J. S. J. Am. Chem. Soc.
2000, 122, 11315.
(3) (a) Chandrasekhar, S.; Sadashiva, B. K.; Suresh, K. A. Pramana 1977,
7, 471. (b) Mindyuk, O. Y.; Stetzer, M. R.; Heiney, P. A.; Nelson, J. C.;
Moore, J. S. AdV. Mater. 1998, 10, 1363. (c) Lehn, J.-M.; Maltheˆte, J.;
Levelut, A. M.; J. Chem. Soc., Chem. Commun. 1985, 1794. (d) van
Nostrum, C. F. AdV. Mater. 1996, 8, 1027.
(7) (a) Ho¨ger, S.; Enkelmann,V. Angew. Chem. 1995, 107, 2917; Angew.
Chem., Int. Ed. Engl. 1995, 34, 2713. (b) Morrison, D. L.; Ho¨ger, S. J.
Chem. Soc., Chem. Commun. 1996, 2313.
(8) Ho¨ger, S.; Meckenstock, A.-D.; Mu¨ller, S. Chem. Eur. J. 1998, 4,
2421.
10.1021/ja003990x CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/22/2001

5652 J. Am. Chem. Soc., Vol. 123, No. 24, 2001
Ho¨ger et al.
Scheme 1a
a Reagents and conditions: (a) i: TIPS acetylene, Pd(0) (cat.), Cu(I) (cat.), piperidine; ii: TMS acetylene, 84%; (b) K2CO3, MeOH, THF, 94%;
(c), Pd(0) (cat.), Cu(I) (cat.), piperidine, 86%; (d) Bu4NF, THF, 94%; (e) Pd(0) (cat.), Cu(I) (cat.), piperidine, 64%; (f) TMS acetylene, Pd(0) (cat.),
Cu(I) (cat.), piperidine, 91%; (g) K2CO3, MeOH, THF, quant.; (h) CuCl, CuCl2, pyridine, 48%; (i) p-TsOH, MeOH, CHCl3, 98%; (j) alkyl halide,
K2CO3, DMF, 14-48%.
Target structures for our investigation of the influence of
different extraannular alkyl side groups on the melting and
solubility properties of large rigid rings are compounds 1a-c
(Scheme 1).
are used to determine the association constants of these
compounds. Per macrocycle, four phenol ether groups are
pointing to the outside and act as connectors for the extraannular
alkyl groups.
They are based on a noncollapsible molecular backbone
having a lumen of about 2 nm. The internal void of the rings is
large enough to incorporate functional groups in a convergent
arrangement,9 and therefore these compounds serve as useful
models for the purpose described above. Each ring contains eight
propyloxy units and two methyl groups which ensure sufficient
solubility of all intermediate compounds. In addition, the methyl
groups simplify the proton NMR spectra in the aromatic region.
This will be important if concentration-dependent NMR spectra
Results and Discussions
Synthesis. As shown in Scheme 1, the Glaser coupling of
the bisacetylenes 11 was used for the cyclization reaction.
However, two synthetic strategies to prepare 1 were considered.
In the first strategy considered, the phenol corner pieces with
the corresponding alkyl substituents could be joined prior to
the ring formation. In this case a quadruple coupling reaction
could be avoided, which may decrease the product yield. In
the second strategy, the phenol macrocycle is formed first (via
oxidative coupling of the tetrahydropyranyl (THP)-protected half
(9) Ho¨ger, S.; Meckenstock, A.-D. Chem. Eur. J. 1999, 5, 1686.

Macrocycles with Extraannular Polyalkyl Substituents
J. Am. Chem. Soc., Vol. 123, No. 24, 2001 5653
rings), followed by its derivatization with the alkyl groups. By
using the second strategy the cyclization reaction had to be
optimized only once. Furthermore, the second strategy was
chosen because the Rf values of the cyclic dimers and the higher
oligomers and polymers are often similar, making the product
purification troublesome in cases where purification by recrys-
tallization or reprecipitation is not possible.
The formation of the bisacetylenes was performed by a bi-
directional synthesis starting from the toluoyl corner piece 5
(Scheme 1). Although the convergent-type synthesis of the
bisacetylenes 11 starting from a protected phenol ether corner
piece similar to 8 might have some advantages,8 the required
starting materials are not as easily available as in the procedure
outlined here.
2-Bromo-5-iodo-1,4-dipropyloxybenzene 210 was treated with
1.1 equiv of triisopropylsilyl (TIPS) acetylene at room temper-
ature, and an additional 2 days at 55 °C. Subsequently, an excess
of trimethylsilyl (TMS) acetylene (2 equiv) was added, and the
mixture was stirred for an additional 2 days at the same
temperature before workup. Deprotection of the TMS group of
this coupling product (3) was performed by stirring with
potassium carbonate in methanol/THF (1:1) overnight. Pal-
ladium-catalyzed coupling of 4 with 3,5-diiodotoluene (5), and
desilylation of 6 by reaction with Bu4NF gave 7.
Protected 3-bromo-5-iodo-phenol, necessary for the selective
coupling using the bromo-iodo strategy, is only available by a
time-consuming multistep reaction starting from trinitrotolu-
ene.11 We therefore explored the possibility to use the much
more available THP-protected 3,5-diiodophenol 8 in an excess
reaction.12 Reaction of a 6-fold excess of 8 with 7 afforded the
diiodo compound 9 in 64% yield after chromatography. The
excess of 8 was almost completely recovered. Palladium-
catalyzed coupling of 9 with TMS acetylene gave 10, from
which the TMS groups were removed with potassium carbonate
in THF/methanol. CuCl/CuCl2-promoted coupling of the half
ring 11 was performed under pseudo-high dilution conditions
at 60 °C and gave the ring 12 in 45-50% yield. Mentioned
previously, this temperature is a compromise between the
increased coupling rate favoring the dimer formation and the
decreased product stability at elevated temperatures.13 Acid-
catalyzed deprotection of the THP groups generated the tet-
raphenol 13 in quantitative yield.
All macrocycles 1 are slightly yellow solids. 1a has a low
solubility in common organic solvents (<1 mg ml-1) and a
melting point of about 220-222 °C. Investigations under the
polarizing microscope gave no indications for the occurrence
of a liquid crystalline (LC) phase.15 Replacement of the four
linear C18-chains by 12 C6-chains does not change the melting
point dramatically, 1b still has a melting point slightly above
200 °C. A meta-stable liquid crystalline phase was observed
when the sample was quenched (15-20 °C/min), but the texture
was fast superimposed by the formation of spherolites.16 If the
ratio of alkyl chains to the rigid backbone is increased, as in
1c, the melting point decreased to 122-126 °C. Even so, a LC-
phase was not observed. All of these observations are consistent
with the notion that the large internal void of the rings hinders
the formation of a stable LC-phase.15
Aggregation. Macrocycle 1a is only moderately soluble in
common organic solvents; whereas, 1b and 1c are readily
soluble in THF and in aromatic and chlorinated solvents. The
proton NMR data in these solvents are concentration-indepen-
dent, giving no indications for the presence of any aggregation
phenomena. However, it has been reported earlier that the
aggregation constant of shape-persistent macrocycles is solvent-
dependent, and solvophobic interactions are also responsible for
the aggregation of self-assembled disk-shaped molecules.5
Although in the case described here, the ratio of the aromatic
backbone to the total surface of the molecule is much smaller
(due to the size of the rings and their large internal void), we
assumed that the aggregation of the macrocycles might be
induced by adding a solvent which solubilizes the peripheric
alkyl side chains and acts as a nonsolvent for the rigid
macrocyclic core of the molecule. Indeed, the proton NMR
spectra in the aromatic region of a solution of 1c in a mixture
of dichloromethane/n-hexane show a strong concentration
dependence that increases as the proportion of the nonpolar
solvent increases. All proton NMR signals remained distinct,
and only a single set of signals was detected, indicating that
aggregate formation and dissociation occurred rapidly on the
NMR time scale. The aggregation constants were determined
by measuring concentration-dependent chemical shifts of the
aromatic protons of the macrocycle. Analysis of the data was
performed under the assumption that the monomer-dimer
equilibrium is the predominant process in solution.17 Whereas
macrocycle 1c shows no aggregation in pure CD2Cl2, solvo-
phobic interactions lead to an aggregation with a dimerization
constant of 130 ( 30 M-1 in CD2Cl2/hexane-d14 (1:3 at 25 °C).
A further polarity decrease of the solvent system by increasing
the volume fraction of hexane increases the dimerization
constant to 790 ( 180 M-1 (in CD2Cl2/hexane-d14 (1:6) at 25
°C). These data indicate that aggregation of the rings can be
enforced by the addition of a solvent that acts as a good solvent
for the alkyl chains and a poor solvent for the core (solvopho-
We investigated three different extraannular alkyl side groups,
which are either commercially available or were prepared.14
Attachment of the side groups was accomplished by potassium
carbonate-catalyzed reaction of 13 with an excess of the
corresponding alkyl halide at 60 °C in DMF. The progress of
the alkylation could be monitored by proton NMR spectroscopy
(see Supporting Information). The proton signals from the
phenolic parts of the ring shifted downfield after the alkylation,
which was complete after 3-4 days. Purification of the rings
was performed by repeated column chromatography. The low
yield of 1a was attributed to its restricted solubility, which
complicated workup and purification.
(15) Ho¨ger, S.; Enkelmann, V.; Bonrad, K.; Tschierske, C. Angew. Chem.
2000, 112, 2356; Angew. Chem., Int. Ed. Engl. 2000, 39, 2268;
(16) In some experiments, the supercooled LC-phase of small portions
of the material could even be observed at room temperature; however, their
detailed investigation was not possible (see Supporting Information).
(17) Nonlinear regression analysis was used to fit the concentration C
against the 1H NMR chemical shifts δ, to iterate the chemical shifts at
infinite dilution (δ0) and complete association (δ∞) to the theoretical equation
(see, e.g.: Martin, R. B. Chem. ReV. 1996, 96, 3043):
(10) Ho¨ger, S.; Bonrad, K.; Scha¨fer, G.; Enkelmann, V. Z. Naturforsch.
1998, 53b, 960. The formation of 3 also has been described by starting
from 2,5-diiodo dipropyloxybenzene: Yu, C. J.; Chong, Y.; Kayyem, J.
F.; Gozin, M. J. Org. Chem. 1999, 64, 2070. Opposite to our synthesis, a
two-step reaction was used involving a statistical coupling reaction, which
diminished the product yield.
(11) Hodgson, H. H.; Winall, J. S. J. Chem. Soc. 1926, 2079.
(12) 3,5-Diiodo phenol was prepared by a modified literature procedure.
Details on the synthesis are reported in the Supporting Information.
(13) Ho¨ger, S.; Bonrad, K.; Karcher, L.; Meckenstock, A.-D. J. Org.
Chem. 2000, 65, 1588.
(14) Balagurusamy, V. S. K.; Ungar, G.; Percec, V.; Johansson, G. J.
Am. Chem. Soc. 1997, 119, 1539.
4KMtot + 1 - 8KMtot + 1
x
δ ) δ0 + (δ∞ - δ0)
(
)
4KMtot
The addition of the nonsolvent hexane rapidly decreases the solubility of
the compound. Therefore, the NMR signals could not be detected at higher
concentrations, giving rise to an additional uncertainty of the dimerization
constants.

5654 J. Am. Chem. Soc., Vol. 123, No. 24, 2001
Ho¨ger et al.
Figure 1. Schematic presentation of the solvent-induced macrocycle
dimerization.
bically induced aggregation, Figure 1).18,19 However, it must
be pointed out that a further increase of the association constants
by decreasing the volume fraction of the polar solvent is not
possible due to the limited solubility of 1c in hexane. Neverthe-
less, control of the degree of aggregation and ordering is indeed
possible in this system that combines solvophobically induced
aggregation with the formation of a soluble shell of the alkyl
substituents.
This approach widely extends the possibility to form complex
superstructures by the organization of cyclic moieties since it
does not require a special electronic substitution pattern on the
ring. Ongoing studies with rings containing noncrystallizable
side groups will show if this approach can be extended toward
the formation of hollow, cylinder-like molecular objects by a
solvent-induced self-organization process.3d,6,19
Adsorption. A different approach toward the control of the
organization of shape-persistent macrocycles is the formation
of regular two-dimensional arrays. As Moore has shown, shape-
persistent macrocycles with extraannular phenolic groups can
form (quasi-) two-dimensional structures in the solid state. The
driving force for this arrangement is the interaction of the polar
groups of the macrocycles leading to an extended hydrogen-
bonded network.20
However, the organization of nonfunctionalized rigid cyclic
structures requires another driving force. One possible meth-
odology should be the assembly of the objects at the air-water
interface. Contrary to the expectations, Moore’s phenylacetylene
macrocycles studied on a Langmuir-Blodgett trough adopt at
the interface an edge-on orientation, while the face-on orienta-
tion is not stable.21
Another approach toward regular 2D structures would be the
adsorption of macrocycles from solution to the surface of highly
oriented pyrolytic graphite (HOPG). In the case of our oligo-
alkyl substituted rings we expected that the lateral intermolecular
interaction of the peripheric alkyl side chains and the balance
between these groups and the hydrophobic HOPG substrate
would drive the macrocycles to form well-ordered structures.22
Ultimately, these 2D structures may provide a tool for epitaxially
induced supramolecular 3D structures.23
Figure 2. Monolayer domain structure of compound 1c adsorbed from
solution onto graphite. STM height image, size of 90 nm × 90 nm,
height range 0.5 nm, I ) 8 pA, U ) -500 mV.
(001) surface. High-resolution scanning tunneling microscopy
(STM) images show clearly two-dimensional structures of the
macrocycles. The molecular image usually appeared im-
mediately after bringing the solution of the ring in 1,2,4-
trichlorobenzene onto the HOPG surface. During the first scan
the image contrast of the 1c adsorbates on HOPG varied
spontaneously, yielding only fuzzy pictures. Then the observed
structure was rather stable during repeated scanning by the STM
tip at sufficiently low tunneling currents. Figure 2 shows a
representative in situ STM image of a large scan area depicting
boundaries between different domains. Within the domains
superstructural arrays are seen aligned along particular direc-
tions. The angle between domain directions is 120° ( 3°,
corresponding to the hexagonal graphite symmetry.24
To study the arrangement of the molecules relative to the
graphite lattice the underlying graphite was investigated by
lowering the bias voltage (50 mV) at increased tunneling current
(60 pA) (see inset in Figure 3). The high-resolution STM images
reveal that the molecular rows were oriented with an angle of
31 ( 3° to the main crystallographic direction of the graphite.
The peripheric alkyl tails of the macrocycles were oriented along
the atomic rows of HOPG (001). The two-dimensional unit cell
is of oblique symmetry (plane group p12mm), containing one
macrocyclic molecule. The lattice constants were determined
to be A ) 3.6 ( 0.2 nm, B ) 5.7 ( 0.2 nm, and Γ ) 74 ( 3°.
Since the two-dimensional elementary cell is filled with only
one molecue, the plane group implies C2 symmetry for each
molecule, including its alkyl periphery. These data suggest that
the molecules cover the surface in the form of a densely packed
monolayer with a tight arrangement of the alkyl chains that lie
between the rows of the rings. A model of the molecular
arrangement of the rings derived from the STM pictures is
depicted in Figure 4. The size of individual macrocycle
measured by STM is in agreement with the dimensions of the
aromatic ring backbone determined by single-crystal X-ray
analysis in similar compounds.7a,15
Indeed, 1c can be adsorbed at the solution-HOPG interface
and forms a highly ordered and stable monolayer on the HOPG
(18) For the solvophobic induced aggregation of branched noncovalent
complexes see, e.g.: (a) Kraft, A.; Osterod, F.; Fro¨hlich, R. J. Org. Chem.
1999, 64, 6425. (b) Palmans, A. R. A.; Vekemans, J. A. J. M.; Havinge, E.
E.; Meijer, E. W. Angew. Chem. 1997, 109, 2763; Angew. Chem., Int. Ed.
Engl. 1997, 36, 2648.
(19) For reviews about low molecular mass organic gelators see, e.g.:
(a) Terech, P.; Weiss, R. G. Chem. ReV. 1997, 97, 3133. (b) Abdallah, D.
J.; Weiss, R. G. AdV. Mater. 2000, 12, 1237.
(20) Venkataraman, D.; Lee, S.; Zhang, J.; Moore, J. S. Nature 1994,
371, 591.
(21) Shetty, A. S.; Fischer, P. R.; Stork, K. F.; Bohn, P. W.; Moore, J.
S. J. Am. Chem. Soc. 1996, 118, 9409.
(22) For 2D crystals of large polycyclic aromatic hydrocarbons on HOPG
see, e.g.: Vivekanantan, S. I.; Yoshimura, K.; Enkelmann, V.; Epsch, R.;
Rabe, J. P.; Mu¨llen, K. Angew. Chem. 1998, 110, 2843; Angew. Chem.,
Int. Ed. Engl. 1998, 37, 2696;
(23) During the preparation of the manuscript the adsorption of cyclic
thiophene oligomers on HOPG was independently reported by others:
Kro¨mer, J.; Rios-Carreras, I.; Fuhrmann, G.; Musch, C.; Wunderlin, M.;
Debaerdemaeker, T.; Mena-Osteritz; E.; Ba¨uerle, P. Angew. Chem. 2000,
112, 3623; Angew. Chem., Int. Ed. Engl. 2000, 39, 3481.
(24) Spong, J. K.; Mizes, H. A.; LaComb, L. J., Jr.; Dovek, M. M.;
Frommer, J. E.; Foster, J. S. Nature 1989, 338, 137.

Macrocycles with Extraannular Polyalkyl Substituents
J. Am. Chem. Soc., Vol. 123, No. 24, 2001 5655
Figure 3. STM height image of the compound 1c adsorbed on graphite.
Image size 18.8 nm × 18.8 nm, the height range cover 0.5 nm, I ) 8
pA, U ) -500 mV. The inset shows an STM image of the underlying
graphite lattice (side 3 nm, I ) 60 pA, U ) -50 mV).
Figure 5 displays two-high resolution images of the same
region in which each aromatic system of the rings and the alkyl
side chains are clearly visible. The most intriguing feature is
that the unit cells of both micrographs show different contrast.
In general, the image contrast depends on large variations of
tunnel gap resistance (Rgap ) U/I).25 Our case is notable because
only a 5% variation of Rgap affects the image contrast strongly.
In both pictures the contrast variation between the aromatic ring
and the alkyl side chains is clearly visible. Whereas in Figure
5A the cyclic backbone is represented with uniform intensity,
in Figure 5B the diacetylene bridge cannot be seen. Hence, the
contrast in the STM images relies strongly on the local electronic
coupling of the adsorbed molecules with the surface and tip,
and cannot be attributed simply to the topography.26,27 To test
this assumption, the frontier orbitals of the cyclic backbone of
1c have been calculated by the MNDO method. The density of
the lowest unoccupied molecular orbital (LUMO) is uniformly
distributed over the whole ring (Figure 6A), while the density
of the highest occupied molecular orbital (HOMO) exhibits
distinct minima at the two diacetylene bridges (Figure 6B).
Quantitatively, it can be inferred that the contrast is due to the
perturbation of the frontier orbital by the presence of the tip-
HOPG surface. Namely, the LUMO dominates the contrast in
Figure 5A, while the HOMO contributes on the appearance of
Figure 5B.
Figure 4. Possible structure of 1c based on the registry of the alkyl
side chains on the HOPG (001) surface (A and B). The dimensions of
the aromatic backbone of an analogue compound obtained by single-
crystal X-ray analysis are marked (*).
force field (MMFF).29 The single cyclic macrocycle exhibits
two energetically similar nonplanar molecular geometries, which
are denoted the “boat” (Figure 7A) and the “chair” conformation
(Figure 7B); the chair conformation is also found in the solid-
state structure of similar rings.7a,15 Figure 7D shows the potential
curves obtained from the approximation of the macrocycles to
the HOPG surface. At large distances (d > 1.5 nm, d is the
shortest distance between the surface and a point defined as
the intersection of lines between opposite located phenyl rings
of the macrocycle) between substrate and adsorbate the flat
conformation (Figure 7C) is less stable than the boat and the
chair conformation by about 30 kJ/mol. However, this situation
changes dramatically when the macrocycles were brought in
contact with a graphite surface. Due to their nonplanar geometry
the latter cannot approach the surface closely (d > 0.6-0.8 nm),
To understand the effect of the HOPG surface on the
macrocycle, computer simulations of the cyclic backbone were
performed with MacroModel 7.028 using the Merck molecular
(25) At low magnification the interaction tip-sample, due to the scanning
speed, affects the ordering of the adsorbed molecules. The true structure of
the monolayer is deduced from the high magnification micrographs showing.
Careful examination shows the presence of local hexagonal symmetry in
all cases.
(26) Foster, J. S.; Frommer, J. E. Nature 1988, 333, 542.
(27) (a) Lazzaroni, R.; Calderone, A.; Lambin, G.; Rabe, J. P.; Bre´das,
J. L. Synth. Met. 1991, 525, 41. (b) Lazzaroni, R.; Calderone, A.; Bre´das,
J. L.; Rabe, J. P. J. Phys. Chem. 1997, 107, 99.
(28) Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.;
Lipton, M.; Caulfield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J.
Comput. Chem. 1990, 11, 440.
(29) Halgren, T. A. J. Comput. Chem. 1996, 17, 490.

5656 J. Am. Chem. Soc., Vol. 123, No. 24, 2001
Ho¨ger et al.
Figure 5. STM height images of 1c on the HOPG (001) surface. Scan
area: 10.4 nm × 10.4 nm. (A) I ) 8.79 pA and U ) -1 V, (B) I )
9.24 pA and U ) -1 V.
Figure 6. (A) LUMO, and (B) HOMO of the cyclic backbone of 1c.
Result of the MNDO calculation using SPARTAN1.3.5.
while the flat conformation can reach a minimum distance of
0.4 nm. The calculated difference in adsorption enthalpy is larger
than the difference of the three conformations. Hence, the
potential curves predict the transition from the nonplanar to the
flat conformation during the adsorption process. The driving
force for this change in molecular conformation is the optimiza-
tion of the contact area between the aromatic units and the
graphite surface, since the aliphatic units were not considered
in the calculation (see Supporting Information).30
The use of functionalized macrocycles for the preparation of
functionalized nano-patterned surfaces is in progress.
Conclusions
We have described the synthesis of shape-persistent macrocy-
cles with four phenol OH groups pointing to the outside,
allowing the attachment of alkyl- and branched oligoalkyl-sub-
stituents to the rings. In solution, the aggregation of the macro-
cycles can be influenced by changing the solvent properties. In
good solvents for both the stiff core and the flexible extraannular
alkyl chains (CD2Cl2), no aggregation was observed. However,
by adding a nonsolvent with respect to the core (n-hexane-d14),
the rings tend to aggregate. The degree of association increases
as the polarity of the solvent mixture decreases.
Our STM investigation clearly demonstrates that the macro-
cycle 1c adsorbs on HOPG surface in a two-dimensional ordered
monolayer. The strong interaction between the substrate and
the adsorbates caused a sufficient flattening of the shape-
persistent macrocycle. The assembly of macrocycles onto the
graphite surface could be a valuable tool for surface patterning
in the nanometer regime. Patterning could be achieved by a
judicious choice of macrocycle size and specific functionality,
allowing one to pattern the surface with a “bottom-up” approach.
(30) Linear paraffins are known to absorb strongly on HOPG. Hence,
the interaction between 1c and HOPG is underestimated by our calculations,
e.g.; Rabe, J. P.; Buchholz, S. Phys. ReV. Lett. 1991, 66, 2096.

Macrocycles with Extraannular Polyalkyl Substituents
J. Am. Chem. Soc., Vol. 123, No. 24, 2001 5657
Figure 7. Boat (A), chair (B), and planar (C) conformation of the macrocycle and potential curves of their approximation to the HOPG sur-
face (D).
low-current RHK 1000 control system. In situ STM imaging was
performed at the internal interface between HOPG and concentrated
solution of 1c dissolved in 1,2,4-trichlorobenzene. A drop of solution
was placed on a freshly cleaved HOPG surface, while the surface had
already been scanned by STM under conditions that allowed atomic
resolution of the graphite surface structure. A potential of V ) ( 1 V
was applied to the substrate. The scan rate was varied between 0.2 and
0.6 µm/s. The tunneling current set point was 8-20 pA. All images
presented were obtained at constant current mode using a Pt/Ir (90/
10)-tip, which was mechanically sharpened. The specific tunneling
conditions are given in the figure captions. Molecular Modeling was
performed with MacroModel 7.0,28 using the Merck molecular force
field (MMFF).29 Structure optimization was performed by application
of the Polak-Ribier algorithm31 to random start conformations until a
final gradient below 0.005 kJ/Å was reached. The structure was refined
further by means of the Truncated Newton conjugate gradient methode32
until the final gradient was below 0.005 kJ/Å. A HOPG surface was
simulated by two layers of polycyclic aromates of sufficient lateral
extension to cover the adsorbed species. Semiempirical calculations
were done with SPARTAN 5.1.3, using the MNDO option. The default
convergence criterion was used (rms change in density matrix <0.001,
self-consistent field energy convergence: <10-6 eV. No symmetry
condition was applied. Convergence criterion was met after 3494
cycles).
1,4-Dipropyloxy-2-(2-triisopropylsilylethynyl)-5-(2-trimethylsi-
lylethinyl)benzene (3). Pd(PPh3)2Cl2 (300 mg) and CuI (150 mg) were
added to a solution of 4-bromo-2,5-dipropyloxy-iodobenzene (12.0 g,
30.0 mmol), triisopropylsilylacetylene (5.85 g, 32.0 mmol), and PPh3
(300 mg) in piperidine (60 mL) at 0 °C. The mixture was allowed to
reach room temperature and was stirred for 2 days, followed by an
additional 2 days at 55 °C. Then trimethylsilylacetylene (5.89 g, 60.0
mmol) was added, and the mixture was stirred for an additional 2 days
at the same temperature. After the reaction mixture cooled to room
temperature, ether and water were added. The organic phase was
separated and extracted with water, 10% acetic acid, water, 10%
Apart from the possibility to organize the macrocycles by
aggregation, it is possible to use the adsorption on HOPG to
obtain a two-dimensional arrangement of the rings. Our previous
work on the synthesis of functionalized macrocycles should
enable us to pattern the surface on a nanoscale with various
functionalities, and subsequently use these structures as a
platform for the formation of 3D supramolecular structures.
Experimental Section
General Methods. Commercially available chemicals were used as
received. THF was distilled from potassium prior to use. Piperidine
and pyridine were distilled from CaH2 and stored under argon. 1H NMR
and 13C NMR spectra were recorded on Bruker AC-300 (300 MHz for
proton 75.48 MHz for carbon). Thin-layer chromatography was
performed on aluminum plates precoated with Merck 5735 silica gel
60 F254. Column chromatography was performed with Merck silica gel
60 (230-400 mesh). Radial chromatography was performed with Merck
silica gel 60 PF254 containing CaSO4. The gel permeation chromato-
grams were measured in THF (flow rate 1 mL min-1) at room
temperature, using a combination of three styragel columns (porosity
103, 105, and 106) and an UV detector operating at λ ) 254 nm. The
molecular weight was obtained from polystyrene calibrated SEC
columns. The matrix-assisted laser desorption ionization time-of-flight
measurements were carried out on a Bruker reflex spectrometer (Bruker,
Bremen), incorporating a 337 nm nitrogen laser with a 3 ns pulse
duration (106-107 W cm-1, 100 µm spot diameter). The instrument
was operated in a linear mode with an accelerating potential of 33.65
kV. The mass scale was calibrated using polystyrene (Mp ) 4700),
using a number of resolved oligomers. Samples were prepared by
dissolving the macrocycle in THF at a concentration of 10-4 mol L-1
.
Then 10 µL of this solution and 10 µL of a 10-3 mol l-1 silver
trifluoroacetate solution were added to 10 µL of a 0.1 mol L-1 matrix
solution, dissolved in THF. In all cases 1,8,9-trihydroxyanthracene
(Aldrich, Steinheim) was used as matrix. Then1 µL of this mixture
was applied to the multistage target and airdried. Microanalysis was
performed by the University of Mainz. Scanning tunneling microscopy
(STM) measurements were carried out at ambient conditions with a
(31) Polak, E.; Ribiere, G. ReV. Franc. Informat. Rech. Operat. 1969,
35, 16.
(32) Ponder, J. W.; Richardson, F. M. J. Comput. Chem. 1987, 8, 1016.

5658 J. Am. Chem. Soc., Vol. 123, No. 24, 2001
Ho¨ger et al.
aqueous sodium hydroxide, water, and brine, and then dried over
MgSO4. Evaporation of the solvent yielded a brown residue that was
filtered over silica gel with petroleum ether/ether (10:1) as the eluent
(Rf ) 0.90) and recrystallized from methanol to give 4 as a colorless
of the solvent yielded a slightly yellow oil, which was chromatographed
over silica gel with hexanes/CH2Cl2 (2:1) as the eluent (Rf ) 0.77).
The solvent was removed to give 8 as colorless solid (12.1 g, 86%)
1
mp 57-59 °C; H NMR (300 MHz, CD2Cl2) δ 7.68 (m, 1 H), 7.39
1
powder (11.9 g, 84%) mp 89 °C; H NMR (CD2Cl2) δ 6.92 (s, 1 H),
(m, 2 H), 5.37 (t, J ) 3.0 Hz, 1 H), 3.79 (m, 1 H), 3.59 (m, 1 H),
2.00-1.60 (m, 6 H); 13C NMR (75.45 MHz, CD2Cl2) δ 158.05, 138.37,
125.45, 96.81, 94.26, 62.09, 30.16, 25.13, 18.49; MS (FD) m/z 430.0
[M+] Anal. Calcd for C11H12O2I2 (430.02): C, 30.72; H, 2.81. Found:
C, 30.69; H, 2.75.
6.90 (s, 1 H), 3.93 (t, J ) 6.5 Hz, 2 H), 3.91 (t, J ) 6.5 Hz, 2 H), 1.80
(m, 4 H), 1.15 (s, 21 H), 1.07 (t, J ) 7.4 Hz, 3 H), 0.26 (s, 9 H);13C
NMR (CD2Cl2) δ 154.61, 154.07, 117.92, 116.90, 114.43, 114.11,
103.08, 101.31, 99.98, 96.70, 71.36, 71.06, 22.89, 22.82, 18.60, 11.57,
10.48, 10.41, -0.27. MS (EI) m/z ) 470.2 (75) [M+], 427.1 (29), 385.2
(25), 343.1 (22), 315.1 (15), 298.9 (15), 270.9 (17), 73.0 (100). Anal.
Calcd for C30H46O2Si2 (470.84): C, 71.43; H, 9.85. Found: C, 71.06;
H, 9.81.
3,5-Bis-[2-(2,5-dipropyloxy-4-{2-[5-iod-3-(tetrahydro-2H-pyran-
2-yloxy)phenyl]ethynyl}phenyl)ethynyl]toluene (9). Pd(PPh3)2Cl2 (40
mg) and CuI (20 mg) were added to a solution of 8 (9.50 g, 22.1 mmol),
7 (2.10 g, 3.68 mmol), and PPh3 (40 mg) in piperidine (20 mL), and
the mixture was stirred for 12 h at 60 °C. Workup was performed as
described for compund 6. The oily crude product was chromatographed
over silica gel with CH2Cl2/hexanes (1:2) as the eluent to recover most
of the excess of 8 (Rf ) 0.77). Changing the eluent to CH2Cl2/hexanes
(1:1) yielded as second fraction (Rf ) 0.50) 9 as a slightly yellow solid
1,4-Dipropyloxy-2-ethynyl-5-(2-triisopropylsilylethynyl)ben-
zene (4). Compound 3 (4.71 g, 10.0 mmol) was dissolved in MeOH/
THF (1:1, 30 mL), K2CO3 (4.1 g, 30 mmol) was added, and the mixture
was stirred overnight. The mixture was poured into ether and water,
and the organic layer was extracted with water and brine. Drying over
MgSO4 and subsequent evaporation of the solvent yielded a yellow
residue that was purified by column chromatography over silica gel
with hexanes/CH2Cl2 (7:1) as the eluent (Rf ) 0.34) to give 5 as a
1
(2.77 g, 64%). H NMR (300 MHz, CD2Cl2) δ 7.51 (t, J ) 1.5 Hz, 2
H), 7.50 (m, 1 H), 7.41 (dd, 1J ) 1.3 Hz, 2J ) 1.5 Hz, 2 H), 7.34 (m,
2 H), 7.19 (dd, 1J ) 1.2 Hz, 2J ) 2.3 Hz, 2 H), 7.04 (s, 2 H), 7.03 (s,
2 H), 5.41 (t, J ) 3.1 Hz, 2 H), 4.00 (t, J ) 6.4 Hz, 8 H), 3.84 (m, 2
H), 3.63 (m, 2 H), 2.37 (s, 3 H), 2.00-1.60 (m, 20 H), 1.11 (t, J ) 7.2
Hz, 6 H), 1.10 (t, J ) 7.2 Hz, 6 H); 13C NMR (75.45 MHz, CD2Cl2)
δ 157.52, 153.88, 153.82, 138.83, 133.44, 132.25, 131.42, 126.30,
126.00, 123.71, 118.93, 117.21, 117.25, 114.33, 113.74, 96.87, 94.24,
93.52, 92.95, 87.11, 86.28, 71.32, 62.19, 30.29, 25.22, 22.83, 20.92,
18.68, 10.43; MS (FD) m/z 1176.3 [M+]. Anal. Calcd for C61H62I2O8
(1176.96): C, 62.25; H, 5.31. Found: C, 62.48; H, 5.32.
1
slightly yellow solid (3.75 g, 94%) mp 97 °C; H NMR (300 MHz,
CD2Cl2) δ 6.94 (s, 2 H), 3.94 (t, J ) 6.5 Hz, 2 H), 3.91 (t, J ) 6.5 Hz,
2 H), 3.37 (s, 1 H), 1.81 (m, 4 H), 1.15 (m, 21 H), 1.07 (t, J ) 6.5 Hz,
3 H), 1.05 (t, J ) 6.5 Hz, 3 H); 13C NMR (75.45 MHz, CD2Cl2) δ
154.31, 154.16, 117.68, 117.59, 114.85, 112.88, 102.95, 96.83, 82.25,
80.12, 71.33, 71.15, 22.85, 22.82, 18.64, 11.76, 10.73, 10.40; MS (FD)
m/z 398.1 [M+]. Anal. Calcd for C25H38O2Si (398.66): C, 75.32; H
9.61. Found C, 75.32; H, 9.68.
3,5-Bis-{2-[2,5-dipropyloxy-4-(2-triisopropylsilylethynyl)phenyl]-
ethynyl}toluene (6). Pd(PPh3)2Cl2 (150 mg) and CuI (80 mg) were
added to a solution of 4 (8.02 g, 20.1 mmol), 3,5-diiodotoluene (3.27
g, 9.50 mmol), and PPh3 (150 mg) in piperidine (100 mL). The solution
was stirred for 24 h at room temperature and then poured into ether
and water. The organic phase was separated and extracted with water,
10% acetic acid, water, 10% aqueous sodium hydroxide, water, and
brine. Drying over MgSO4 and evaporation of the solvent yielded an
oily residue that was chromatographed over silica gel with CH2Cl2/
hexanes (1:3) as the eluent (Rf ) 0.42) to give 6 as a slightly yellow
solid (7.2 g, 86%). 1H NMR (300 MHz, CD2Cl2) δ 7.47 (s, 1 H), 7.32
(br s, 2 H), 6.98 (s, 2 H), 6.96 (s, 2 H), 3.98 (t, J ) 6.5 Hz, 4 H), 3.94
(t, J ) 6.5 Hz, 4 H), 2.36 (s, 3 H), 1.83 (m, 8 H), 1.15 (m, 42 H), 1.10
(t, J ) 7.4 Hz, 3 H), 1.05 (t, J ) 7.4 Hz, 3 H); 13C NMR (75.45 MHz,
CD2Cl2) δ 154.93, 154.13, 139.29, 132.68, 131.87, 124.25, 118.29,
117.27, 114.88, 114.47, 103.61, 97.27, 94.47, 86.87, 71.89, 71.61, 23.40,
23.33, 21.43, 12.03, 10.99, 10.95; MS (FD) m/z 885.3 [M+].
3,5-Bis-[2-(2,5-dipropyloxy-4-{2-[3-(tetrahydro-2H-pyran-2-yloxy)-
5-(2-trimethylsilylethynyl)phenyl]ethynyl}phenyl)ethynyl]toluene (10).
Pd(PPh3)2Cl2 (20 mg) and CuI (10 mg) were added to a solution of 9
(1.05 g, 0.93 mmol), TMS acetylene (0.55 g, 5.6 mmol), and PPh3 (20
mg) in piperidine (20 mL), and the mixture was stirred for 12 h at 60
°C. Workup was performed as described for compund 6. Column
chromatography over silica gel with CH2Cl2/hexanes (1:1) as the eluent
(Rf ) 0.54) gave 10 as a slightly yellow oil which slowly solidified
(0.95 g, 91%). 1H NMR (300 MHz, CD2Cl2) δ 7.50 (m, 1 H), 7.34 (m,
2 H), 7.24 (m, 2 H), 7.18 (dd, 1J ) 1.5 Hz, 2J ) 2.3 Hz, 2 H), 7.12 (m,
2 H), 7.04 (s, 3 H), 7.03 (s, 3 H), 5.43 (m, 2 H), 4.01 (t, J ) 6.5 Hz,
8 H), 3.86 (m, 2 H), 3.63 (m, 2 H), 2.38 (s, 3 H), 2.00-1.60 (m, 20
H), 1.12 (t, J ) 7.5 Hz, 6 H), 1.11 (t, J ) 7.5 Hz, 6 H), 0.26 (s, 18 H);
13C NMR (75.45 MHz, CD2Cl2) δ 157.02, 153.83, 138.83, 132.23,
131.41, 128.26, 124.64, 124.50, 123.73, 120.08, 120.00, 117.25, 114.17,
113.96, 104.01, 96.73, 94.88, 94.16, 93.85, 86.43, 86.30, 71.32, 62.17,
30.34, 29.26, 22.84, 20.93, 18.75, 10.42, -0.36; MS (FD) m/z 1117.0
[M+].
3,5-Bis-[2-(2,5-dipropyloxy-4-{2-[3-(tetrahydro-2H-pyran-2-yloxy)-
5-ethynylphenyl]ethynyl}phenyl)ethynyl]toluene (11). Compound 11
was prepared by the procedure described for 4, with 10 (1.50 g, 1.34
mmol), K2CO3 (0.93 g, 6.7 mmol) and MeOH/THF (1:1, 40 mL).
Purification was performed by column chromatography (silica gel) with
hexanes/ethyl acetate (3:1) as the eluent (Rf ) 0.62) to give 11 in nearly
quantitative yield as a slightly yellow oil that slowly solidified. 1H NMR
(300 MHz, CD2Cl2) δ 7.50 (br s, 1 H), 7.35 (br s, 2 H), 7.28 (m, 2 H),
7.22 (m, 2 H), 7.16 (m, 2 H), 7.04 (m, 4 H), 5.42 (m, 2 H), 4.01 (t, J
) 6.1 Hz, 8 H), 3.86 (m, 2 H), 3.61 (m, 2 H), 3.15 (s, 2 H), 2.38 (s,
3 H), 1.50-2.00 (m, 20 H), 1.12 (t, J ) 7.2 Hz, 3 H), 1.11 (t, J ) 7.2
Hz, 3 H); 13C NMR (75.45 MHz, CD2Cl2) δ 157.08, 153.89, 153.83,
138.83, 132.23, 131.42, 128.39, 124.77, 123.72, 123.42, 120.50, 120.25,
117.27, 114.24, 113.89, 96.84, 94.19, 93.71, 86.54, 86.29, 82.68, 77.53,
71.33, 62.23, 30.35, 25.25, 22.84, 20.92, 18.79, 10.43; MS (FD) m/z
972.7 [M+]. Anal. Calcd for C65H60O8 (973.21): C, 80.22; H, 6.63.
Found: C, 80.30; H, 6.91.
3,5-Bis-[2-(2,5-dipropyloxy-4-ethynylphenyl)-ethynyl]toluene (7).
A 1 M solution of Bu4NF in THF (13.5 mL, 13.5 mmol) was added to
a solution of 6 (3.00 g, 3.39 mmol) in THF (20 mL). The mixture was
stirred for 2 h at room temperature and then poured into ether and
water. The organic layer was extracted with water and brine and dried
over MgSO4. Evaporation of the solvent yielded a slightly yellow-brown
oil, which was purified by chromatography over silica gel with hexanes/
CH2Cl2 (1:1) as the eluent (Rf ) 0.72) to give 7 as a slightly yellow
1
solid (1.82 g, 94%) mp 112 °C; H NMR (300 MHz, CD2Cl2) δ 7.49
(m, 1 H), 7.34 (m, 2 H), 7.02 (s, 2 H), 7.00 (s, 2 H), 3.98 (t, J ) 6.5
Hz, 4 H), 3.97 (t, J ) 6.5 Hz, 4 H), 3.40 (s, 2 H), 2.37 (s, 3 H), 1.84
(m, 8 H), 1.10 (t, J ) 7.4 Hz, 6 H), 1.06 (t, J ) 7.4 Hz, 6 H); 13C
NMR (75.45 MHz, CD2Cl2) δ 154.28, 153.64, 138.82, 132.26, 131.42,
123.66, 118.02, 117.09, 114.50, 112.91, 94.08, 86.09, 82.36, 80.01,
71.30, 71.20, 22.82, 22.72, 20.92, 10.41, 10.31; MS (FD) m/z 572.2
[M+] Anal. Calcd for C39H40O4 (572.74): C, 81.79; H, 7.04. Found:
C, 81.76; H, 7.08.
3,5-Diiodo-(tetrahydro-2H-pyran-2-yloxy)benzene (8). p-Tolu-
enesulfonic acid (∼30 mg) was added to a solution of 3,5-diiodophenol
(11.3 g, 32.7 mmol) and of 3,4-dihydro-(2H)-pyran (13.5 g, 160 mmol)
in CH2Cl2 (100 mL) at 0 °C. The solution was stirred for 2 h at this
temperature and subseqently for 45 min at room temperature before
being poured into ether and 10% aqueous sodium hydroxide. The
organic phase was separated and washed with 10% aqueous sodium
hydroxide, water, and brine and then dried over MgSO4. Evaporation
THP-Protected Macrocycle 12. A solution of 11 (1.8 g, 1.85 mmol)
in pyridine (35 mL) was added to a suspension of CuCl (10.2 g, 103
mmol) and CuCl2 (2.0 g, 15 mmol) in pyridine (250 mL) over 96 h at
60 °C. After the completion of the addition, the mixture was allowed
to stir for an additional 4 d at room temperature and then was poured
into CH2Cl2 and water. The organic phase was extracted with water,
25% NH3 solution (in order to remove the copper salts), water, 10%

Macrocycles with Extraannular Polyalkyl Substituents
J. Am. Chem. Soc., Vol. 123, No. 24, 2001 5659
acetic acid, water, 10% aqueous sodium hydroxide, and brine and dried
over MgSO4. After evaporation of the solvent to about 30 to 40 mL,
the coupling products were precipitated by the addition of methanol
(200 mL) and collected by filtration. Recrystallization from pyridine
mg, 0.55 mmol) in DMF (130 mL). Purification was performed by
repeated column chromatography over silica gel with hexanes/CH2Cl2
(2:3) as the eluent (Rf ) 0.24) to give 1b as a slightly yellow powder
(190 mg, 48%) mp 202-204 °C; 1H NMR (300 MHz, CD2Cl2) δ 7.53
(m, 2 H), 7.36 (t, J ) 1.4 Hz, 4 H), 7.34 (dd, 1J ) 1.4 Hz, 2J ) 0.8 Hz,
4 H), 7.17 (dd, 1J ) 2.5 Hz, 2J ) 1.4 Hz, 4 H), 7.11 (dd, 1J ) 2.5 Hz,
2J ) 1.4 Hz, 4 H), 7.05 (m, 8 H), 6.63 (m, 8 H), 4.05-3.90 (m, 40 H),
2.38 (s, 6 H), 1.95-1.65 (m, 40 H), 1.55-1.25 (m, 72 H), 1.13 (t, J )
7.4 Hz, 12 H), 1.12 (t, J ) 7.4 Hz, 12 H), 0.91 (m, 36 H); 13C NMR
(75.45 MHz, CD2Cl2) δ 158.82, 153.96, 153.85, 153.50, 138.89, 138.18,
131.93, 131.34, 128.83, 125.22, 123.72, 123.00, 119.09, 118.53, 117.27,
114.45, 113.71, 106.16, 94.28, 93.44, 87.03, 86.28, 80.97, 74.02, 73.48,
71.35, 70.86, 69.27, 31.90, 31.73, 30.43, 29.53, 25.90, 22.87, 22.81,
22.75, 20.96, 13.95, 13.90, 10.45; MS (MALDI-TOF) m/z 3275.48 [M
+ Ag+]; C210H260O24 (3168.30).
Macrocycle 1c. Compound 1c was prepared by the procedure
described for 1a, by adding K2CO3 (690 mg, 5.0 mmol) to a solution
of 13 (200 mg, 125 µmol) and 3,4,5-tridodecyloxy benzyl chloride (373
mg, 0.55 mmol) in DMF (130 mL). Purification was performed by
repeated column chromatography over silica gel with hexanes/CH2Cl2
(1:1) as the eluent (Rf ) 0.36) to give 1a as a slightly yellow solid
(167 mg, 32%) mp 122-126 °C; 1H NMR (300 MHz, CD2Cl2) δ 7.52
(m, 2 H), 7.36 (t, J ) 1.4 Hz, 4 H), 7.34 (dd, 1J ) 1.4 Hz, 2J ) 0.8 Hz,
4 H), 7.17 (dd, 1J ) 2.5 Hz, 2J ) 1.4 Hz, 4 H), 7.11 (dd, 1J ) 2.2 Hz,
2J ) 1.4 Hz, 4 H), 7.05 (m, 8 H), 6.63 (s, 8 H), 4.98 (s, 8 H), 4.05-
3.90 (m, 40 H), 2.38 (s, 6 H), 1.95-1.65 (m, 40 H), 1.50-1.20 (m,
216 H), 1.12 (t, J ) 7.4 Hz, 12 H), 1.13 (t, J ) 7.4 Hz, 12 H), 0.88
(m, 36 H); 13C NMR (125 MHz, CD2Cl2) δ 158.79, 153.94, 153.82,
153.47, 138.87, 138.13, 132.00, 131.31, 128.84, 125.20, 123.71, 122.98,
119.06, 118.49, 117.24, 114.41, 113.67, 106.13, 94.26, 93.43, 87.02,
86.26, 80.96, 74.02, 73.47, 71.31, 70.84, 69.23, 32.05, 30.48, 29.87,
29.82, 29.77, 29.56, 29.49, 26.25, 22.85, 22.81, 20.94, 13.97, 10.45;
MS (MALDI-TOF) m/z 4287.7 [M + Ag+]; C282H404O24 (4178.35).
1
gave 12 as a slightly yellow solid (0.86 g; 48%) mp 240 °C dec; H
NMR (300 MHz, CD2Cl2) δ 7.49 (m, 2 H), 7.34 (m, 4 H), 7.32 (m, 4
H), 7.25 (m, 4 H), 7.22 (m, 4 H), 7.12 (s, 4 H), 7.11 (s, 4 H), 5.52 (m,
4 H), 4.04 (t, J ) 6.2 Hz, 16 H), 3.83 (m, 4 H), 3.62 (m, 4 H), 2.37 (s,
6 H), 2.00-1.50 (m, 40 H), 1.14 (t, J ) 7.5 Hz, 24 H); 13C NMR
(75.45 MHz, d8-THF) δ 158.29, 154.89, 154.79, 139.46, 132.85, 132.37,
129.71, 126.18, 124.94, 123.64, 121.28, 120.80, 117.88, 115.28, 114.74,
97.40, 94.70, 94.06, 87.82, 87.28, 81.57, 74.49, 71.77, 62.37, 31.03,
26.10, 23.63, 21.05, 19.40, 10.93; MS (MALDI-TOF) m/z 2052.4 [M
+ Ag]+.
Macrocycle 13. To a suspension of 12 (500 mg, 0.26 mmol) in
CHCl3 (200 mL) was slowly added MeOH (15 mL) and then
p-toluenesulfonic acid (10-15 mg). The mixture was stirred for 3 d at
room temperature under an argon atmosphere. Methanol was added,
and the yellow precipitate was collected by filtration and vacuum-dried
in the dark to give 13 as a slightly yellow solid (436 mg; 98%) mp
1
240 °C dec; H NMR (300 MHz, d7-DMF, 80 °C) δ ) 10.10 (br s, 4
H), 7.55 (s, 2 H), 7.43 (m, 4 H), 7.28 (m, 12 H), 7.13 (m, 8 H), 4.15
(t, J ) 6.3 Hz, 8 H), 4.14 (t, J ) 6.3 Hz, 8 H), 2.43 (s, 6 H), 1.95-
1.80 (m, 16 H), 1.15 (m, 24 H); 13C NMR (75.45 MHz, d7-DMF, 80
°C) δ 159.51, 155.23, 140.45, 132.90, 132.60, 127.90, 126.25, 124.98,
123.74, 120.80, 120.30, 119.06, 119.01, 115.57, 115.38, 95.10, 94.77,
87.91, 87.83, 82.36, 74.60, 72.58, 23.73, 21.34, 11.13; MS (MALDI-
TOF) m/z 1712.9 [M + Ag]+.
Macrocycle 1a. K2CO3 (520 mg, 3.7 mmol) was added to a solu-
tion of 13 (150 mg, 94 µmol) and stearylbromide (138 mg, 0.42 mmol)
in DMF (60 mL) at 60 °C and stirred for 4 d at the same temperature
in the dark. After the reaction mixture cooled to room temperature,
CH2Cl2 and water were added. The organic phase was separated and
extracted with water and brine and dried over MgSO4. After evaporation
of the solvent the residue was chromatographed over silica gel with
hexanes/CH2Cl2 (1:3) as the eluent (Rf ) 0.57) to give 1a as a slightly
yellow powder (34 mg, 14%): mp 220-222 °C; 1H NMR (300 MHz,
CD2Cl2) δ 7.54 (m, 2 H), 7.33 (m, 4 H), 7.32 (m, 4 H), 7.09 (m, 4 H),
7.06 (m, 8 H), 7.04 (m, 4 H), 4.08-3.98 (m, 24 H), 2.39 (s, 6 H),
2.00-1.75 (m, 24 H), 1.45-1.25 (m, 120 H), 1.14 (t, J ) 7.6 Hz, 24
H), 0.90 (m, 12 H); 13C NMR (75.45 MHz, CD2Cl2) δ 159.30, 154.06,
153.98, 138.91, 132.02, 128.40, 125.17, 123.83, 123.00, 118.83, 118.39,
117.48, 117.42, 114.53, 113.97, 94.30, 93.66, 86.86, 86.36, 81.09, 73.93,
71.50, 68.79, 41.36, 32.09, 29.85, 29.81, 29.75, 29.72, 29.50, 29.27,
26.11, 22.93, 22.83, 13.97, 10.47; MS (FD) m/z 2614.5 [M+];
Acknowledgment. Financial support by the VW-Stiftung
for a part of this work is gratefully acknowledged. We also thank
Professor P. Ba¨uerle for access to the STM.
Supporting Information Available: Synthetic schemes for
1
diiodophenol, H NMR spectra for 13 and 1a, texture of the
metastable LC-phase of 1b, NMR dilution experiments for 1c
in CD2Cl2/hexanes (1:3) and CD2Cl2/hexanes (1:6), energy-
minimized structures and energetic parameters of the macro-
cyclic ring, additional calculated potential curves of the
macrocyclic ring in the presence of HOPG (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
C182H236O12 (2615.81).
Macrocycle 1b. Compound 1b was prepared by the procedure
described for 1a, by adding K2CO3 (690 mg, 5.0 mmol) to a solution
of 13 (200 mg, 125 µmol) and 3,4,5-trihexyloxy benzyl chloride (234
JA003990X