Hierarchical self-assembly of a bow-shaped molecule bearing self-complementary hydrogen bonding sites into extended supramolecular assemblies

Article abstract of DOI:10.1002/chem.200400826

The bow-shaped molecule 1 bearing a self-complementary DAAD-ADDA (D = donor A = acceptor) hydrogen-bonding array generates, in hydrocarbon solvents, highly ordered supramolecular sheet aggregates that subsequently give rise to gels by formation of an entangled network. The process of hierarchical self-assembly of compound 1 was investigated by the concentration and temperature dependence of UV-visible and ¹H NMR spectra, fluorescence spectra, and electron microscopy data. The temperature dependence of the UV-visible spectra indicates a highly cooperative process for the self-assembly of compound 1 in decaline. The electron micrograph of the decaline solution of compound 1 (1.0 mM) revealed supramolecular sheet aggregates forming an entangled network. The selected area electronic diffraction patterns of the supramolecular sheet aggregates were typical for single crystals, indicative of a highly ordered assembly. The results exemplify the generation, by hierarchical self-assembly, of highly organized supramolecular materials presenting novel collective properties at each level of organization.

Full text of DOI:10.1002/chem.200400826

Hierarchical Self-Assembly of a Bow-Shaped Molecule Bearing Self-
Complementary Hydrogen Bonding Sites into Extended Supramolecular
Assemblies
Masato Ikeda,[a, c] Tadahito Nobori,[a, d] Marc Schmutz,[b] and Jean-Marie Lehn*[a]
Abstract: The bow-shaped molecule 1
bearing a self-complementary DAAD–
ADDA (D=donor A=acceptor) hy-
drogen-bonding array generates, in hy-
drocarbon solvents, highly ordered
supramolecular sheet aggregates that
subsequently give rise to gels by forma-
tion of an entangled network. The
process of hierarchical self-assembly of
compound 1 was investigated by the
concentration and temperature de-
pendence of UV-visible and 1H NMR
spectra, fluorescence spectra, and elec-
tron microscopy data. The temperature
dependence of the UV-visible spectra
indicates a highly cooperative process
for the self-assembly of compound 1 in
decaline. The electron micrograph of
the decaline solution of compound 1
(1.0mm) revealed supramolecular sheet
aggregates forming an entangled net-
work. The selected area electronic dif-
fraction patterns of the supramolecular
sheet aggregates were typical for single
crystals, indicative of a highly ordered
assembly. The results exemplify the
generation, by hierarchical self-assem-
bly, of highly organized supramolecular
materials presenting novel collective
properties at each level of organiza-
tion.
Keywords:
hydrogen bonds
·
molecular recognition · self-assem-
bly · supramolecular chemistry ·
supramolecular polymers
Introduction
noncovalent interactions, that may have liquid-crystal fea-
tures.[1–9] Hydrogen-bonded supramolecular polymeric
chains were realized first through complementary, triple hy-
drogen-bonding ADA–DAD arrays (D: hydrogen-bonding
donor; A: hydrogen-bonding acceptor) and gave rise to
supramolecular liquid crystals.[5a]
For the structural features of liquid crystalline mesophas-
es, the shape of individual molecules is crucial. In particular,
rigid molecules of bent shape (“banana-shaped” com-
pounds[10]) may form liquid crystals with a unique alignment
that confers potential application for ferro- or antiferroelec-
tric switching. Similarly, the shape of the monomeric mole-
cules determines the morphology and ordering of supra-
molecular polymeric associations. The self-assembly of a
number of such supramolecular polymers from linear-, disk-,
macrocyclic-, and helical-shaped molecules has been de-
scribed.[8,9] The self-assembly of rigid bent-shaped molecules
could yield supramolecular polymers with interesting elec-
tronic and optical material properties as well as unique
structural features.
Hierarchical self-assembly of molecules in a supramolecular
network represents a versatile approach for developing well-
defined polymolecular architectures with preprogrammed
arrangements and tailored properties. Particular attention
has been paid to supramolecular polymers, materials derived
from the polyassociation of monomeric components through
[a] Dr. M. Ikeda, Dr. T. Nobori, Prof. Dr. J.-M. Lehn
Laboratoire de Chimie Supramolꢀculaire
ISIS, Universitꢀ Louis Pasteur
8, allꢀe Gaspard Monge, BP 70028
67083 Strasbourg Cedex (France)
Fax : (+33)390-245-140
E-mail: lehn@isis.u-strasbg.fr
[b] Dr. M. Schmutz
Institut Charles Sadron, CNRS
6, rue Boussingault, 67083 Strasbourg Cedex (France)
[c] Dr. M. Ikeda
Because of its versatility and directionality, hydrogen
bonding is a suitable noncovalent interaction for generating
supramolecular polymers. Since the degree of polymeriza-
tion is strongly dependent on the strength of association, the
number and the pattern of hydrogen bonds are important
Present address: ERATO (Yashima Super-Structured Helix)
Creation Core Nagoya 2266–22 Aza-Anagahora Shimoshidami
Moriyama-ku Nagoya 463–0003 (Japan)
[d] Dr. T. Nobori
Present address: Material Science Laboratory, Mitsui Chemicals
662
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/chem.200400826
Chem. Eur. J. 2005, 11, 662 – 668

FULL PAPER
factors to obtain high degrees of polymerization. As indicat-
ed above, the first example of linear hydrogen-bonded
supramolecular polymers were derived from complementary
triple hydrogen-bonding ADA–DAD arrays.[5a] Strong com-
plementary quadruple hydrogen bonding DDAA–AADD or
DADA–ADAD arrays have extensively studied and the re-
sulting supramolecular polymers have very concentration-
and temperature-dependent viscosity.[9] Sextuple hydrogen
bonding has been implemented between two-faced symmet-
rical heterocomplementary components, with DAD/DAD
and ADA/ADA patterns.[6] As most of these studies have
concerned the polyassociation of symmetrical monomers
bearing complementary hydrogen-bonding sites (such as
Scheme 1. Structure of the monomer
DAAD–ADDA patterns of hydrogen bonding sites and its directional
self-assembly into ribbon-like supramolecular polymer through an
1 bearing self-complementary
ADA-(spacer)-ADA
+ DAD-(spacer)-DAD or DDAA-
a
(spacer)-AADD), the supramolecular polymers formed
were also symmetric and possessed no directionality. In con-
trast, a supramolecular polymer derived from a monomer
bearing two different self-complementary hydrogen-bonding
faces will induce directional assembly, because of their non-
symmetric polyassociation. In biology, it bears analogy to
the integrated network formed by the supramolecular poly-
mer filament of actin, responsible for the mechanical integri-
ty of the cell and critically involved in such processes as cell
division, mobility, and plasticity.[11]
array of four hydrogen bonds.
known to enforce a highly preferred transoid conformation
around a,a’-interheterocyclic bonds,[12] thus conferring the
orientation required for establishing the self-complementary
array of hydrogen bonds to the heterocyclic subunits in 1
(Scheme 2).
We thus envisioned that the self-assembly of bow-shaped
molecules bearing self-complementary hydrogen-bonding
patterns would allow the generation of a highly organized,
directional supramolecular architecture. To this end, com-
pound 1 was designed. It has a rigid bent-shape and self-
complementary quadruple hydrogen-bonding DAAD–
ADDA arrays and thus is expected to undergo polar supra-
molecular self-assembly as shown in Scheme 1. The structur-
al codon represented by the pyridine–pyrimidine moiety is
Scheme 2. Preferred conformation of compound 1.
Herein, we report that compound 1 indeed forms highly
ordered supramolecular sheet aggregates in hydrocarbon
solvents in a cooperative manner and subsequently gives
rise to gels with an entangled network of these supramolec-
ular sheet aggregates.
Abstract in French: La molꢀcule 1 prꢀsente une forme
courbe en arc et porte un ensemble autocomplꢀmentaire
DAAD–ADDA de liaisons hydrogꢁne. En solution hydrocar-
bonꢀe, elle gꢀnꢁre des feuillets supramolꢀculaires hautement
ordonnꢀs qui ensuite produisent des gels par formation dꢂun
rꢀseau enchevÞtrꢀ. Le processus dꢂautoassemblage hiꢀrarchisꢀ
du composꢀ 1 a ꢀtꢀ ꢀtudiꢀ par lꢂexamen des modifications des
spectres UV-visible, de RMN et de fluorescence en fonction
de la concentration et de la tempꢀrature, ainsi que par micro-
scopie ꢀlectronique. La variation des spectres UV-visible en
fonction de la tempꢀrature indique que lꢂautoassemblage de 1
dans la dꢀcaline est un processus hautement coopꢀratif. La
micrographie ꢀlectronique du sol formꢀ par 1 dans la dꢀcali-
ne (1.0 mm) rꢀvꢁle la formation dꢂagrꢀgats supramolꢀculaires
en feuillets constituant un rꢀseau enchevÞtrꢀ. La diffraction
ꢀlectronique de ces agrꢀgats fournit des images typiques de
cristaux, indiquant que lꢂensemble est hautement ordonnꢀ.
Les rꢀsultats obtenus illustrent la genꢁse, par autoassemblage
hiꢀrarchisꢀ, de matꢀriaux supramolꢀculaires hautement orga-
nisꢀs prꢀsentant de nouvelles propriꢀtꢀs collectives ꢃ chaque
niveau dꢂorganisation.
Results and Discussion
Synthesis of compounds 1 and 2: Compound 1 was synthe-
sized according to Scheme 3. Treatment of 2-amino-6-bromo
pyridine with dodecanoic acid chloride gave the amide 3a,
which was converted into the stannyl derivative 4a by reac-
tion with hexamethylditin in the presence of a [Pd(PPh3)4]
catalyst. Double coupling of 2.1 equivalents of 4a with Boc-
protected 2-amino-4,6-dichloropyrimidine (5) in the pres-
ence of [Pd(PPh3)4] catalyst led to the Boc-protected com-
pound 1 in 67% yield; subsequent deprotection by treat-
ment with trifluoracetic acid (TFA) gave the desired com-
pound 1 in 84% yield. Compound 2, bearing shorter chains,
was obtained following the same pathway.
Hierarchical and cooperative self-assembly of compound 1
1H NMR spectroscopy in chloroform: The self-assembly of
compound 1 was first investigated by evaluating the concen-
Chem. Eur. J. 2005, 11, 662 – 668
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
663

J.-M. Lehn et al.
ing a monomer–dimer equilibrium,[13] yielding a small asso-
ciation constant of 20mꢀ1, which is coincident with the asso-
ciation constant between Boc-protected 1 and 2-aminopy-
1
rimidine (18mꢀ1) (vide infra). In addition, all H NMR sig-
nals remained sharp even at 250mm, showing that higher
order aggregations beyond the dimer were negligible in
these conditions.
Remarkable up-field shifts were also observed for the sig-
nals of the alkyl chain protons, especially for the protons
close to the amide groups (Figure 1). Such up-field shifts
were not observed for the complexation between Boc-pro-
tected 1 and 2-aminopyrimidine (data not shown). There-
fore, the observed up-field shifts do not result from the hy-
drogen bonding interaction, but from a shielding effect of
the pyridine rings as shown in Figure 2. These results agree
Scheme 3. i) RCOCl, Py, CH2Cl2, room temperature; ii) Me3SnSnMe3,
5mol% [Pd(PPh3)4], PhMe, 1108C; iii) (Boc)2O, DMAP, CH2Cl2, room
temperature; iv) 5mol% [Pd(PPh3)4], DMF, 1108C; v) TFA, CH2Cl2,
room temperature.
1
tration dependence of H NMR spectra in chloroform. At
1.0mm, compound 1 showed a clearly resolved spectrum,
corresponding to a molecular solution. On increasing the
concentration of 1 up to 250mm, significant and correlated
down-field shifts were observed for both the amide-NH and
the pyrimidine-NH2 signals (Figure 1), indicating that self-
Figure 2. Schematic representation of the shielding effect due to the pyri-
dine rings.
with the formation by compound 1 of well-defined self-as-
sembled supramolecular assemblies through self-comple-
mentary quadruple hydrogen bonding as expected
(Scheme 1).
Gelation properties of compound 1: The self-assembly of
compound 1 in nonpolar solvents, in which hydrogen-bond-
ing strength should be markedly enhanced, was then investi-
gated by examining its gelation ability. The powder of com-
pound 1 was dispersed in a given solvent (10.0mm), the mix-
ture was heated in a septum-capped test tube and then
cooled to room temperature. Compound 1 was found to
gelate hydrocarbon solvents such as decaline (mixture of
cis- and trans-isomer), toluene, p-xylene, and paraffin. In
contrast, compound 2 was not able to form a gel. The long
alkyl chains play an important role in gel formation in the
hydrocarbon solvents, presumably by preventing the crystal-
lization of the compound. The gels of compound 1 were
opaque not transparent, suggesting the presence of micro-
scale aggregates. These aggregates displayed a birefringent
character in the polarized optical micrograph of the decaline
gel of compound 1, indicating that they possessed a certain
Figure 1. 400 MHz 1H NMR spectra of
b) 1.0mm (s: solvent, inset: concentration dependence of chemical shift
of the amide protons) at 258C.
1 in [D1]CHCl3 a) 250.0mm,
assembly through hydrogen bonding was taking place and
can be explained by the interaction mode depicted in
Scheme 1. The plot of the chemical shift of the amide-NH
signal against concentration was tentatively analyzed assum-
664
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 662 – 668

Hierarchical Self-Assembly
FULL PAPER
extent of molecular ordering. The most stable gels were ob-
tained with decaline as solvent; they were stable at room
temperature for one month without precipitation. The gel
formation was completely reversible with temperature.
These results led us to evaluate the self-assembly properties
of compound 1 in decaline in detail by spectroscopic and mi-
croscopic methods.
sorption spectroscopy measurements were performed. Rais-
ing the temperature of a solution of compound 1 (0.10mm)
in decaline from 258C to 658C resulted in blue shifts of the
absorption bands, from 312.0 to 307.0 and 313.0 nm and
from 355.0 to 343.0 nm, with a clear isosbestic point at
364.5 nm (Figure 4). At 658C, the spectrum had almost the
UV-visible spectra of compound 1 in decaline: The aggrega-
tion behavior of compound 1 was studied by using UV-visi-
ble spectroscopy, monitoring the changes in the p!p* tran-
sitions. As shown in Figure 3, the UV-visible abbsorption
Figure 4. Temperature dependent UV-visible spectra of compound
1
(0.10mm) in decaline (inset: absorbance at 349.0 nm at different tempera-
tures).
same band shape as in chloroform at room temperature. In-
terestingly, it was found that a S-shaped transition took
place around 458C (Tm), indicating that the formation of
self-assembled aggregates by compound 1 in decaline was
cooperative, that is, the self-assembled aggregates dissociate
to the monomeric comound 1 in an all-or-nothing manner.
The origin of a cooperative behavior may be attributed to
the synergistic operation of hydrogen bonding and p–p
stacking interactions in the self-assembly of compound 1.
Figure 3. UV-visible spectra (top) and fluorescence spectra (bottom)
(lex =340.0 nm) of 1 (0.10mm) in a) chloroform and b) decaline at 258C.
Electron microscopy of the gel formed by compound 1: To
obtain insight into the microstructure of the gel formed by
compound 1, it was investigated by electron microscopy.
Since a freeze–fracture image of compound 1 decaline gel
could not be obtained, a direct observation of compound 1
in decaline (1.0mm) was carried out.
The electron micrograph obtained revealed lamellar mor-
phologies with an average width of 1.0 mm and thickness
probably around 30 nm, since they are transparent to elec-
trons (Figure 5). Very interestingly, the selected area elec-
tron diffraction pattern (inset of Figure 5) of the supra-
molecular sheet aggregates yields a clear high-resolution dif-
fraction pattern, indicating a highly ordered self-assembly.
The pattern indicates a unit cell with orthogonal projection.
The cell parameters are a=9.6, b=16.1 ꢂ (a axis is parallel
to the length of the crystal).
spectrum of compound 1 in decaline (0.10mm) was different
from that in chloroform. From the concentration depend-
1
ence of the UV-visible spectra (data not shown ) and the H
NMR spectrum (vide supra), it was confirmed that com-
pound 1 was moleculary dissolved in this concentration
range in chloroform. Red shifts (from 304.5 to 312.0 nm and
from 345.0 to 355.0 nm) of the absorption bands in decaline
with respect to those in chloroform were observed and a
shoulder appeared around 378.0 nm. This result is consistent
with an enhanced p-electronic conjugation of compound 1
resulting from an increased planarity due to the aggregation
with hydrogen bonding and most probably to so-called J-
type aggregation. Fluorescence spectra gave a red-shifted
emission band around 403.0 nm in decaline relative to that
in chloroform (400.0 nm).
Since molecular modeling calculations based on the supra-
molecular polymerization mode depicted in Scheme 1 sug-
gested a width of about 20 ꢂ for individual supramolecular
To obtain further insight into the self-assembly of com-
pound 1 in decaline, temperature-dependent UV-visible ab-
Chem. Eur. J. 2005, 11, 662 – 668
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
665

J.-M. Lehn et al.
ened at room temperature (gel state) and underwent, when
the sample was heated from room temperature to 1008C, a
significant sharpening due to the dissociation of the self-as-
sembled aggregates. The gel collapsed above 808C; howev-
er, the sample was still turbid, indicating that self-assembled
aggregates exist after the sol–gel transition. The sample
became transparent above 908C, and the spectrum at 1008C
had almost the same peak shape as that of compound 1
(1.0mm) in chloroform. Both amide-NH and pyrimidine-
NH2 proton NMR signals appeared around 608C and shifted
first to lower-field (8.03 to 8.17 ppm: Dd=0.14 ppm for
amide-NH and 4.32 to 4.36 ppm: Dd=0.04 ppm for pyrimi-
dine-NH2) up to 808C and then to higher-field (8.17 to
7.78 ppm: Dd=ꢀ0.39 ppm for amide-NH and 4.36 to
4.32 ppm: Dd=ꢀ0.04 ppm for pyrimidine-NH2) from 808C
to 1008C. Hydrogen bonding in the gel at room temperture
Figure 5. Electron micrograph of compound 1 in decaline (1.0mm) ob-
tained by the direct observation technique, (inset: selected area electron
diffraction pattern).
was confirmed by an FTIR measurement (hydrogen-bonded
ꢀ1
ꢀ
N H stretching band 3230 cm and C=O stretching bands
1663 and 1630 cmꢀ1). These spectral results, together with
the microscopic image, suggest that compound 1 forms en-
tangled and laminated self-assembled supramolecular sheets
with hydrogen bonding and p–p stacking in the gel state at
room temperature. On raising the temperature up to 808C,
this network of self-assembled supramolecular sheets, which
is responsible for the gel formation, would collapse to indi-
vidual self-assembled supramolecular sheets as suggested by
the change of macroscopic properties (from gel to opaque
solution). This structural change would lead to downfield
shifts of the amide-NH and pyrimidine-NH2 signals by loss
of the shielding effect due to p–p stacking. The upfield
shifts, observed when the temperature is raised from 808C
to 1008C, correspond to breaking of the hydrogen bonds on
dissociation of the self-assembled supramolecular sheets
into monomeric compound 1 units.
sheets, the structures observed here could be ascribed as
large bundles of the individual supramolecular sheets.
Presumably, the bow-shape and the self-complementary
hydrogen bonding sites of compound 1 play an important
role in the generation of such a highly ordered supramolec-
ular sheet structure, as evidenced by electron diffraction
(Figure 5). Molecular modeling calculations suggested that
the self-assembly of compound 1 did not lead to a flat supra-
molecular sheet owing to steric hindrance between pyridine
rings and alkyl chains (Figure 2). Nonetheless, supramolec-
ular sheet aggregates were observed even in a chiral solvent
(b-pinene; data not shown here); the most probable explan-
ation is that compound 1 forms a zig-zag type self-assembly
not a helical one, which would generally form fiber aggre-
gates instead of sheet aggregates.
Variable-temperature 1H NMR spectra of compound 1 in
decaline: The H NMR spectra of compound 1 (10 mm) in
Conclusion
1
[D18]decaline were measured in order to elucidate its self-as-
sembly process (Figure 6). The signals were strongly broad-
In conclusion, we have shown that compound 1 forms supra-
molecular sheet aggregates in hydrocabon solvents by direc-
tional assembly through a self-
complementary, quadruple hy-
drogen-bonding
DAAD–
ADDA array (Scheme 1) and
subsequently leads to supra-
molecular gels by formation of
an entangled and laminated
network of the supramolecular
sheet aggregates. Most interest-
ingly, the supramolecular sheet
aggregates
obtained
were
highly organized. This kind of
dissymmetric, directional self-
assembled structure with high
molecular organization is of in-
terest as model of biological
self-assembly, such as that
1
Figure 6. : Variable temperature 400 MHz H NMR spectra of compound 1 (10.0mm) in [D18]decaline.
666
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 662 – 668

Hierarchical Self-Assembly
FULL PAPER
degassed DMF (10 mL) were heated at 1108C for 15 h. The reaction mix-
ture was concentrated under vacuum. The resulting solid was dissolved in
chloroform and subjected to chromatography (Al2O3, n-hexane/ethyl ace-
tate=20:1). Recrystallization from MeOH gave Boc-protected com-
pound 1 as a white solid. Yield: 1.80 g (67%); 1H NMR (400 MHz,
[D1]CHCl3): d=8.92 (s, 1H), 8.37 (d, J=8.2 Hz, 2H), 8.20 (d, J=7.6 Hz,
2H), 8.07 (s, 2H), 7.87 (t, J=7.8 Hz, 2H), 2.46 (t, J=7.6 Hz, 4H), 1.77
(m, 4H), 1.42 (s, 18H), 1,24 (m, 32H), 0.85 ppm (t, J=6,4 Hz, 6H); FAB
MS: m/z calcd for [M+H]+: 844.6; found: 844.5.
found in actin filaments, as well as for the development of
functional supramolecular entities, presenting novel emerg-
ing properties (such as optical,[14] magnetic,[15] ferroelectric,
etc.) at each level of organization.
Experimental Section
Trifluoroacetic acid (1.14 g, 20 equiv) was added to a solution of the Boc-
protected compound 1 (422 mg, 0.5 mmol) in dichloromethane (8 mL).
The reaction mixture was stirred at room temperature for 6 h. It was
then washed with a saturated aqueous solution of NaHCO3 (10 mL) and
water (10 mL). The solvent was evaporated under vacuum. The resulting
solid was recrystalized from 1-propanol to give the desired compound 1
as a white solid. Yield: 270 mg (84%); m.p. 179.7–180.58C; 1H NMR
(400 MHz, [D1]CHCl3): d=8.37 (s, 1H), 8.33 (d, J=8.2 Hz, 2H), 8.25
(brs, 2H), 8.07 (d, J=7.2 Hz, 2H), 7.84 (t, J=8.2 Hz, 2H), 5.21 (brs,
2H), 2.33 (t, J=7.6 Hz, 4H) 1.70 (m, 4H), 1.25 (m, 32H), 0.85 ppm (t,
J=6.4 Hz, 6H); FAB HRMS: m/z calcd for [M+H]+: 644.46520; found
644.46435; elemental analysis calcd (%) for C38H57N7O2: C 70.88, H 8.92,
N 15.23; found: C 70.84, H 9.01, N 15.05.
General methods: All commercially available products were used with-
out further purification. Flash column chromatography was performed on
silica gel (40–63 mm, Merck). Melting points were recorded on a Bꢃchi
1
Melting Point B-540 apparatus and uncorrected. 400 MHz H NMR spec-
tra were recorded on a Bruker Avance 400 spectrometer. The solvent
signal was used as an internal reference. UV-visible and fluorescence
spectra were measured with Varian Cary 3 and Aminco-Bowman Series 2
spectrometers, respectively. FAB mass spectrometric measurements were
performed by the Service de Spectromꢀtrie de Masse, Institut de Chimie,
Universitꢀ Louis Pasteur.
Electron microscopy—direct observation: A 5 mL drop of a solution of
the compound under investigation (1.0mm) in decaline was deposited
onto a 400 mesh EM grid covered with a carbon supporting film. To
allow for sample adsorption, the excess solution was removed with a
piece of filter paper (Whatman 2 or 5), and the grids were air dried. They
were then placed in an Edwards Auto 306 Evaporator and rotary shad-
owed at an angle of 138 with platinum/tungsten. The grids were observed
with a Philips CM12 electron microscope operating at 120 kV.
2-Amino-4,6-bis[6-(ethyrylamino)pyridine-2-yl]pyrimidine (2): Com-
pound 2 was synthesized by a similar procedure to that described for
1
compound 1. M.p. >268.08C (decomp.); H NMR (400 MHz, [D1]CHCl3/
[D6]DMSO): d=9.50 (s, 1H), 8.14 (s, 1H), 8.01 (d, J=7.8 Hz, 2H), 7.78
(d, J=7.8 Hz, 2H), 7.53 (t, J=7.8 Hz, 2H), 5.42 (brs, 2H), 2.33 (m, 4H),
0.93 ppm (t, J=7.8 Hz, 6H); FAB HRMS: m/z calcd for [M+H]+:
392.18350; found: 392.18363.
Synthetic procedures
N-(6-bromopyridin-2-yl)dodecylamide (3a): 2-Amino-6-bromopyridine
(1.73 g, 10.0 mmol) and pyridine (2.10 mL, 26.0 mmol) were dissolved in
dry dichloromethane (40 mL), and the solution was cooled to 58C in an
ice bath. A solution of lauroyl chloride (2.84 g, 13.0 mmol) was added
dropwise, and the reaction was allowed to proceed at room temperature
for 15 hours. The reaction mixture was washed with water (2ꢄ50 mL)
and a aturated aqueous solution of NaHCO3, and the organic layer was
dried over Na2SO4. The solvent was removed under vacuum. n-Hexane
was added to the residual oil to afford compound 3a as white solid.
Yield: 3.29 g (93%); m.p. 67.8–69.18C; 1H NMR (400 MHz, [D1]CHCl3):
d=8.16 (d, J=8.4 Hz, 1H), 7.80 (s, 1H), 7.53 (t, J=7.7 Hz, 1H), 7.18 (d,
J=7.6 Hz, 1H), 2.34 (t, J=7.7 Hz, 2H) 1.67 (m, 2H), 1.24 (m, 16H),
0.86 ppm (t, J=7.0 Hz, 3H); FAB MS: m/z calcd for [M+H]+: 355.1;
found: 355.1
Acknowledgement
We thank Dr. Raymond Hueber for HRMS measurements and Dr. Arno
Tuchbreiter for POM measurements. M.I. thanks Dr. Ibon Odoriozola,
Jean-Louis Schmitt, and Adrian-Mihail Stadler for their kind support and
the JSPS for a Research Fellowship for Young Scientists.
[1] J.-M. Lehn, Supramolecular Chemistry, VCH, Weinheim, Germany,
1995.
[2] a) Supramolecular Polymers (Ed.: A. Cifferi), Marcel Dekker, New
York, 2000; b) J.-M. Lehn, Polym. Int. 2002, 51, 825–839.
[3] M. J. Krische, J.-M. Lehn, Struct. Bonding 2000, 94, 3–29.
[4] L. Brunsveld, B. J. B. Folmer, E. W. Meijer, R. P. Sijbesma, Chem.
Rev. 2001, 101, 4071–4098.
[5] a) C. Fouquey, J.-M. Lehn, A.-M. Levelut, Adv. Mater. 1990, 2, 254–
257; b) M. Kotera, J.-M. Lehn, J.-P. Vigneron, J. Chem. Soc. Chem.
Commun. 1994, 197–199; c) U. Kumar, T. Kato, J. Frꢀchet, J. Am.
Chem. Soc. 1992, 114, 6630–6639.
N-[6-(Trimethylstannanyl)pyridin-2-yl]dodecylamide (4a): Compound 3a
(1.00 g, 2.82 mmol), hexamethylditin (2.92 g, 1.5 equiv), and tetrakis(tri-
phenylphosphino)palladium (161 mg, 0.141 mmol, 5 mol%) in degassed
toluene (25 mL) were heated at 1108C for 15 h. The reaction mixture
was concentrated under vacuum. The resulting solid was dissolved in
chloroform and subjected to chromatography (Al2O3, n-hexane/ethyl ace-
tate=20:1). Compound 4a was obtained as a white solid. Yield: 850 mg
(69%); m.p. 58.9–59.98C; 1H NMR (400 MHz, [D1]CHCl3): d=8.03 (m,
1H), 7.85 (brs, 1H), 7.51 (m, 1H), 7.15 (m, 1H), 2.38 (m, 2H), 1.70 (m,
2H), 1.25 (m, 16H), 0.84 (m, 3H), 0.25 ppm (m, 9H); FAB MS: m/z
calcd for [M+H]+: 439.2; found: 441.2
[6] V. Berl, M. Schmutz, M. J. Krische, R. G. Khoury, J.-M. Lehn,
Chem. Eur. J. 2002, 8, 1227–1244.
[7] Recently, orthogonal self-assemblies of supramolecular polymers in
liquid crystals have been explored. a) T. Kato, Science 2002, 295,
2414–2418; b) N. Mizoshita, H. Monobe, M. Inoue, M. Ukon, T.
Watanabe, Y. Shimizu, K. Hanabusa, T. Kato, Chem. Commun.
2002, 428–429; c) N. Mizoshita, K. Hanabusa, T. Kato, Adv. Funct.
Mater. 2003, 13, 313–317, and references therein.
[8] a) Two-steps self-assembly of columnar entities: M. Suꢅrez, J.-M.
Lehn, S. C. Zimmerman, A. Skoulios, B. Heinrich, J. Am. Chem.
Soc. 1998, 120, 9526–9532; b) Self-assembly of helical monomers:
L. A. Cuccia, J.-M. Lehn, J.-C. Homo, M. Schmutz, Angew. Chem.
2000, 112, 239–243; Angew. Chem. Int. Ed. 2000, 39, 233–237; C.
Nuckolls, T. Katz, J. Am. Chem. Soc. 1998, 120, 9541–9544; c) Self-
asembly of disk-shaped molecules: M. Ikeda, M. Takeuchi, S. Shin-
kai, Chem. Commun. 2003, 1354–1355; L. Brusveld, H. Zhang, M.
Glasbeck, J. A. J. M. Vekemans, E. W. Meijer, J. Am. Chem. Soc.
2-Bis-(tert-butoxycarbonyl)amino-4,6-dichloropyrimidine (5): Di-tert-
butyl dicarbonate (9.62 g, 2.2 equiv) was added to a solution of 2-amino-
4,6-dichloropyrimidine (3.24 g, 19.8 mmol) and 4-dimetylaminopyridine
(244 mg, 0.1 equiv) in dry THF (30 mL). The reaction mixture was stirred
at room temperature for 16 h. Then a small amount of water was added
to the reaction mixture to quench the reaction. The solvent was removed
under vacuum. The resulting residue was subjected to chromatography
(Al2O3, n-hexane/ethyl acetate=50:1–30:1). Compound 5 was obtained
as
a
white solid. Yield: 6.97 g (97%); m.p. 49.1–51.08C; 1H NMR
(400 MHz, [D6]DMSO): d=1.43 (s, 18H), 8.06 ppm (s, 1H); FAB MS:
m/z calcd for [M+H]+: 364.1; found: 364.1
2-Amino-4,6-bis[6-(dodecylamino)pyridine-2-yl]pyrimidine (1): Com-
pound 4a (1.40 g, 3.19 mmol), compound 5 (546 mg, 1.50 mmol), and tet-
rakis(triphenylphosphino)palladium (200 mg, 0.175 mmol, 5 mol%) in
Chem. Eur. J. 2005, 11, 662 – 668
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
667

J.-M. Lehn et al.
2000, 122, 6175–6182; H. Engelkamp, S. Middel beek, R. J. M.
Nolte, Science 1999, 284, 785–788; Y. Yasuda, E. Iishi, H. Inada, Y.
Shirota, Chem. Lett. 1996, 575–576; d) Self-assembly of macrocyclic
molecules: D. T. Bong. T. D. Clark, J. R. Granja, M. R. Ghadiri,
Angew. Chem. 2001, 113, 1016–1041; Angew. Chem. Int. Ed. 2001,
40, 988–1011; S. Lahiri, J. L. Thompson, J. S. Moore, J. Am. Chem.
Soc. 2000, 122, 11315–11319.
suming that the measured chemical shift is the weighted average
that of the monomer and dimer, then the fraction of the species
present as dimer is given by Equation (3) in which di is the mea-
sured chemical shift at concentration ci, while d0 and dd are limiting
chemical shifts of monomer and dimmer, respectively. See: A. S.
Shetty, J. Zhang, J. S. Moore, J. Am. Chem. Soc. 1996, 118, 1019–
1027.
[9] a) R. P. Sijbesma, F. H. Beijer, L. Brunsveld, B. J. B. Folmer, J. H. K.
Ky Hirschberg, R. F. M. Lange, J. K. L. Lowe, E. W. Meijer, Science
1997, 278, 1601–1604; b) J. H. K. Ky Hirschberg, R. A. Koevoets,
R. P. Sijbesma, E. W. Meijer, Chem. Eur. J. 2003, 9, 4222–4231.
[10] a) T. Niori, F. Sekine, J. Watanabe, T. Furukawa, H. Takezoe, J.
Mater. Chem. 1996, 6, 1231–1233; b) G. Pelzl, S. Diele, W. Weissflog,
Adv. Mater. 1999, 11, 707–724.
[11] a) T. P. Loisel, R. Boujemaa, D. Pantaloni, M.-F. Carlier, Nature
1999, 401, 613–616; b) M. O. Steinmetzl, A. Hoenger, P. Tittmann,
K. H. Fuchs, H. Gross, U. Aebil, J. Mol. Biol. 1998, 278, 703–711.
[12] a) G. S. Hanan, J.-M. Lehn, N. Kyritsakas, J. Fischer, J. Chem. Soc.
Chem. Commun. 1995, 765–766; b) D. M. Bassani, J.-M. Lehn, G.
Baum, D. Fenske, Angew. Chem. 1997, 109, 1931–1933; Angew.
Chem. Int. Ed. Engl. 1997, 36, 1845–1847; c) M. Ohkita, J.-M. Lehn,
G. Baum, D. Fenske, Chem. Eur. J. 1999, 5, 3471–3481.
Kd
2M
1
M
H
(1)
(2)
G
2
2½M2ꢁ
c
=
+
ꢀ2
2c Kd
c
2½M2ꢁ
2½M2ꢁ d0ꢀdi
=
(3)
c
d0ꢀdd
[14] For instance, second harmonic generation: P. Zhu, H. Kang, A. Fac-
chetti, G. Evmenenko, P. Dutta, T. J. Marks, J. Am. Chem. Soc. 2003,
125, 11496–11497.
[15] For a case of hierarchical generation of magnetic properties, see: M.
Ruben, U. Ziener, J.-M. Lehn, V. Ksenofontov, P. Gꢃtlich, G. B. M.
Vaughan, Chem. Eur. J. 2005, in press.
[13] The curve fitting procedure was used to analyze assuming the di-
merization of compound 1 as below [Eqs. (1) and (2)], in which Kd
is the dimerization constant, c is the total concentration of M. As-
Received: August 11, 2004
Published online: November 25, 2004
668
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 662 – 668