Geminal Bis-ureas as gelators for organic solvents: Gelation properties and structural studies in solution and in the gel state

Article abstract of DOI:10.1002/1521-3765(20000717)6:14<2633::AID-CHEM2633>3.0.CO;2-L

Several geminal bis-urea compounds were synthesised by means of an acid-catalysed condensation of various benzaldehydes with different monoalkylureas. Many of these compounds form thermoreversible gels with a number of organic solvents at very low concent

Full text of DOI:10.1002/1521-3765(20000717)6:14<2633::AID-CHEM2633>3.0.CO;2-L

FULL PAPER
Geminal Bis-ureas as Gelators for Organic Solvents: Gelation Properties and
Structural Studies in Solution and in the Gel State
Franck S. Schoonbeek,[a] Jan H. vanEsch,*[a] Ron Hulst,[b] Richard M. Kellogg,[a] and
Ben L. Feringa*[a]
Abstract: Several geminal bis-urea
compounds were synthesised by means
of an acid-catalysed condensation of
various benzaldehydes with different
monoalkylureas. Many of these com-
pounds form thermoreversible gels with
a number of organic solvents at very low
concentrations (<3mm) and which are
stable to temperatures higher than
1008C. Electron microscopy revealed a
three-dimensional (3D) network of in-
tertwined fibres, which are several tens
of micrometers long and have a width
ranging from approximately 30to
300 nm. The possible aggregate forms
and aggregate symmetries were evalu-
ated by means of molecular mechanics
calculations. 1H NMR, 2D NMR,
13C NMR and 13C-CP/MAS NMR tech-
niques were used to obtain information
about the aggregation and possible ag-
gregate symmetry of geminal bis-ureas
in solution, in the gel state, and in the
solid state.
Keywords: aggregation
´
gels
´
hydrogen bonds ´ molecular model-
ing ´ self-assembly
for gelation is by the design of novel organogelators. Recently,
Hanabusa et al. and our group independently demonstrated
that bis-urea compounds are exceptionally well-suited for the
design of low molecular weight gelators owing to the rigidity,
strength and high directionality of the multiple intermolecular
hydrogen bonds that can be formed.[4, 5] A key feature in the
design of novel gelators appeared to be unidirectional
gelator± gelator interactions, as is most clearly the case in
trans-1,2-cyclohexyl- and 1,2-phenyl-bis(ureido) gelators.[6]
The proximity of the urea groups in these gelating scaffolds,
leads to adoption of a coplanar orientation, which strongly
favours one-dimensional aggregation through hydrogen-bond
formation (Figure 1). However, molecular modelling studies
and experimental results indicate that one-dimensional ag-
gregation by these compounds is prone to polymorphism,
although the 1,2-bis(urea)cyclohexane and 1,2-bis(urea)ben-
zene gelating scaffolds have little conformational freedom
and the actual or dominant aggregate structure in the gels is
not known in detail. So the problem that is faced is not trivial:
is it possible to establish a clear relationship between crystal
structure, gel structure, aggregation in solution and monomer
structure? Reports on crystal structures of gelator molecules
have been scarce up to now, and we were able to demonstrate
in one case that the arrangement of gelator molecules in the
crystal does not correspond fully with the molecular arrange-
ment in a gel.[6b, 7, 8]
Introduction
Low molecular weight organic gelling agents are currently the
subject of much attention, not only because of the numerous
applications of gels, but also because gelation phenomena by
low molecular weight organic gelling agents are still poorly
understood.[1, 2, 3] These organogelators have in common that
in organic solvents they self-assemble into long fibre-like
structures through highly specific noncovalent interactions,
such as hydrogen bonding and p ± p stacking. These fibres
then entangle to form a three-dimensional (3D) network
which retains the solvent within the pores through capillary
forces. The molecular structures of known (very potent)
organogelators are, however, very diverse, and often structur-
ally closely related compounds do not exhibit any gelation
properties. Most of the research has thus focussed on the
exploration of the molecular diversity of organogelators, but
many of these studies are hampered by the lack of knowledge
on the self-assembly properties of the compounds under study.
A different approach towards a better understanding of
organogels and the elucidation of the molecular prerequisites
[a] Dr. J. H. vanEsch, Prof.Dr. B. L. Feringa, F. S. Schoonbeek,
Prof. Dr. R. M. Kellogg
Department of Organic and Molecular Inorganic Chemistry Stratingh
Institute, University of Groningen, Nijenborgh 4
9747 AG Groningen (The Netherlands)
Fax : (‡31)50-363-4296
E-mail: esch@chem.rug.nl
In the present work we turned our attention to the
aggregation behaviour and gelation capability of novel
geminal bis-urea compounds. For geminal bis-ureas it is
expected that the two urea fragments do not have much
feringa@chem.rug.nl
[b] Dr. R. Hulst
Department of Chemical Analysis, University of Twente P.O. Box 217,
7500 AE Enschede (The Netherlands)
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J. H. van Esch, B. L. Feringa et al.
FULL PAPER
acetamides.[9] This entails an, in principle, rather straightfor-
ward acid-catalysed condensation of a benzaldehyde and the
desired monoalkylurea in refluxing toluene with azeotropic
removal of water (Scheme 1). In most cases, however, a gel
Scheme 1. Synthesis of geminal bis-ureas 1 ± 6.
was formed during the reaction, and 100% conversion to the
desired product was prevented. A decrease in the concen-
tration of the reactants solved this problem for most of the
systems studied. Upon cooling of the reaction mixture a
precipitate or gel-like solid was formed, which could easily be
isolated from the reaction mixture by filtration with suction.
Attempts to synthesise bis-ureas with longer alkyl chains
(octyl, dodecyl) were not successful. Although inspection of
1
Figure 1. Conformational freedom in a 1,2-bis(urea)benzene derivative
and X-ray structure of a 1,2-bis(urea)benzene in the solid state,[6b] clearly
showing the presence of linear hydrogen-bonded aggregates in the solid
state.
samples from these reaction mixtures by H NMR spectro-
scopy revealed that most of the starting materials had
disappeared, no product precipitated from the reaction
mixture upon cooling to room temperature, and all attempts
to isolate the products by other means failed. The most likely
explanation is that these geminal bis-ureas are very sensitive
to the combination of traces of acid and moisture. For
example, dissolving samples of 1 ± 6 in commercial CDCl3
(which contains traces of water and HCl) results in partial or
complete decomposition into the parent aldehyde and alkyl-
urea. In pure, acid-free CDCl3 and in [D6]DMSO (which does
contain some water but no acid) this problem does not exist.
independent rotational freedom owing to their proximity, as
demonstrated for 1,2-bis(urea)cyclohexane and 1,2-bis(urea)-
benzene derivatives. It is extremely likely that the hydrogen-
bonding ability is directed along one intermolecular axis and
therefore should strongly favour one-dimensional aggrega-
tion. The possible gelation of organic solvents by geminal bis-
urea compounds will thus strengthen the concept of unidirec-
tional interactions as a prerequisite for gelation. This know-
ledge will be valuable in the elucidation of the structural
requirements for gelation by other types of gelling agents for
which a first approximation of the directionality of intermo-
lecular interactions is less well defined as with the hydrogen-
bonding systems in the bis-urea compounds.
The second aim of our research on geminal bis-ureas is to
obtain insight in to the relationship between conformation
and aggregation. Here we report on the synthesis of geminal
bis-urea compounds and their gelation capability for organic
solvents, we also report on molecular modelling, and solution
and solid-state NMR studies on their aggregation behaviour
in solution and on the structure of the gels.
Gelation of organic solvents: The gelating ability of geminal
bis-urea compounds 1 ± 6 for a range of organic solvents was
examined (with the exception of 5, which turned out to be too
unstable with respect to hydrolysis) by dissolving approx-
imately 10mg of compound in 1 mL of the desired solvent
under heating. The solubility of these compounds at room
temperature (RT) is very poor in most solvents (chloroform is
a notable exception). Upon cooling to room temperature, a
gel, a precipitate or a clear solution was observed, depending
on the solvent used. In the case of 1, if gelation occurred, the
concentration was gradually lowered until the gelating ability
had disappeared. The results are summarised in Table 1 and
show that a gelator concentration range of 3 ± 15mm is typical,
this has also been found for other bis-urea compounds and
many other organogelators.[1, 4, 6] Apparently these values
represent a lower limit, at which the concentration of these
aggregates is high enough and/or at which the size of the
various aggregates in solution is large enough to sustain a 3D
Results and Discussion
Synthesis: The synthesis of compounds 1 ± 6 was based on a
literature procedure for the preparation of geminal bis-
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Geminal Bis-ureas
2633±2643
Table 1. Gelation properties and critical gelator concentrations.[a]
Solvent
Compound
1
2
3
4
6
hexadecane
cyclohexane
toluene
p-xylene
tetralin
n-butylacetate
1,2-dichloroethane
chloroform
dibutyl ether
acetonitrile
2-octanol
2-propanol
ethanol
DMSO
< 3
< 3
< 5
< 5
< 15
< 5
< 15
s
< 15
p
s (d)
s (d)
s (d)
s
p
p
p
p
p
p
p
s
p
p
s (d)
s (d)
s (d)
s
g
g
s
s
s
s
s
s
p
g
g
g
g(t)
p
g
s
i
g
g
g
g
p
p
s
p
p
s (d)
s (d)
s (d)
s
g
g
g
s
s (d)
s (d)
s (d)
s
s (d)
s (d)
s (d)
s
Figure 2. Melting points of a tetralin gel of 1 as determined by the
dropping ball method.
cyclohexanone
p
s
s
s
p
Schraders equation, which describes ideal solubility behav-
iour, is not justified.[12, 13, 14] Furthermore, a gradual weakening
of the gel is observed by the dropping ball method rather than
a discrete phase transition, in complete agreement with the
results from the DSC experiments.
Light microscopy shows that gels of 1 are birefringent
(indicative of anisotropic properties), as was the case with
previously reported linear bis-ureas, but further structural
details cannot be seen. Electron microscopy (EM) reveals that
compound 1 is able to aggregate into long, intertwining
bundles of fibres which are occasionally split up and fused
with other fibre bundles (junction zones), thus showing that
the network does not result from purely mechanical contacts
between the various fibres (Figure 3). The elongated shape of
[a] Critical gelator concentrations are given in mm. The following
abbreviations are used: d, decomposition; g, gel; i, insoluble; p, precipitate;
s, soluble; t, thixotropic.
network that retains the solvent, and results in the formation
of a gel.[1]
From Table 1 it is clear that only 2 is not an effective
gelator, this may be because the butyl groups in the other
compounds are much more flexible than the benzyl groups
present in 2, and an increased tendency of 2 to crystallise or
precipitate results, rather than gel formation. It is also clearly
demonstrated that none of the compounds 1 ± 6 gelate or
precipitate in the tested protic solvents. NMR analysis of the
solutions revealed that in these solvents 1 ± 6 easily decom-
pose to an acetal and monoalkylurea, both of which are
soluble in protic solvents.
The gels given in Table 1 are stable for at least a few weeks
at room temperature. In some solvents (hexadecane, cyclo-
hexane) the gels are very turbid and are destroyed easily by
mechanical agitation, whereas in tetralin, p-xylene and
toluene the gels are completely transparent and stable
towards agitation. The gel from the methoxy-substituted
compound 4 in tetralin is thixotropic, that is, upon shaking, the
gel loses its rigidity and becomes free flowing. Upon standing
at rest for a few minutes the gel properties returned
completely. This process can be repeated many times.
In all cases gelation was found to be completely thermo-
reversible. Differential scanning calorimetry (DSC) of a
tetralin gel of 1 (80mm) gave a very broad melting endotherm
(Tonset ˆ 908C, Tmax ˆ 1198C, Tend ˆ 1308C) with an enthalpy
change of ‡65 kJmolÀ1. This enthalpy corresponds well with
gelation enthalpies reported previously for bis-urea gelators
in various solvents,[4, 5a] and is about twice as large as the value
that is found for breaking up large aggregates of mono-urea
compounds in an apolar medium.[10] The broad temperature
range of the melting process is indicative of a less cooperative
phase transition.
Figure 3. Electron microscopy photograph of a tetralin gel of 1 (Pt
The relationship between gelator concentration and melt-
ing point of the gel was studied in tetralin by the dropping ball
method (Figure 2).[11] The melting point determined by the
dropping ball method lies approximately 108C below the
maximum of the DSC melting endotherm, and therefore the
evaluation of these data by a phase-separation model or
shadowing, bar is 500 nm).
the fibres most likely results from a strongly anisotropic
growth process, and indicates that the intermolecular inter-
actions are highly directional.[15] Electron microscopy of the
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J. H. van Esch, B. L. Feringa et al.
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various precipitates of 2 revealed that these precipitates
consist of many relatively short crystallites.
FT-IR experiments: The relationship between gelating ability
and intermolecular hydrogen bonding was studied by means
of FT-IR spectroscopy, since the N ± H stretch and the amide-I
and amide-II bands of ureas generally show large shifts upon
the formation of hydrogen bonds. When 1 is dissolved in 1,2-
dichloroethane, we found that at low concentration (4.4mm)
there is a homogeneous solution and no gel is formed. This
solution shows three absorptions at 3436 (N ± H), 1690
(amide-I) and 1512 (amide-II) cmÀ1, which are characteristic
for non-hydrogen-bonded urea groups (Table 2).[16] Increasing
Figure 4. Dihedral angles definition (a) and calculated minimum energy
and saddle point conformations of 7 (b ± d).
Table 2. FT-IR data for 1 in the solid state, in solution and in the gel state.[a]
field as implemented in Quanta97 was carried out by system-
atic variation of f2 and f3, whereas no restrictions were
applied to f1.[18] Only one stable conformation (7a) was
identified by this conformational search, and for symmetry
reasons results in two global energy minima on the potential-
energy surface formed by the dihedral angles f2 and f3. In the
minimum-energy conformation a single hydrogen bond is
present between the two urea groups (Figure 4b). The
rotation of the urea groups around f2 and f3 is marked by
two saddle points (7b, 7c, Figure 4c and 4d) which are
6.3 kcalmolÀ1 and 8.0kcalmol À1 higher in energy.
The interaction potential surfaces of 7a ± c were explored
by calculating the interaction energy between a molecule of 7
located at the centre of a cubic box with a second molecule of
7 while systematically varying the Euler angles of rotation and
repeating this procedure at each point of a cubic box spaced
by 0.5 Š in each direction. The interaction potential surfaces
of the conformers 7a and 7b do not show preferential sites for
complementary hydrogen-bond interactions with a second
molecule. This is in large contrast with 7c, which has a highly
anisotropic interaction potential surface, with the most
favourable sites of interaction being located on the axes
along the urea carbonyl bonds (Figure 5). Similar results have
been obtained for bis-ureas based on 1,2-diaminobenzene and
1,2-diaminocyclohexane.[6b]
Solvent and concentration
Absorptions [cmÀ1
Amide-I
]
NH-stretch
Amide-II
1523
CHCl3, 2.8mm (sol)
ClCH2CH2Cl, 4.4mm (sol)
CHCl3, 47.7mm (sol)
ClCH2CH2Cl, 26.8mm (gel)
Nujol mull
3443
3436
33401639
3306
3343
1667
16901512
1560
1634
1632
1562
1561
[a] All spectra are recorded at RT.
the concentration to 26.8mm results in the formation of a gel,
and the IR spectrum of this gel showed that the urea
adsorption bands are shifted towards 3306, 1634 and
1562 cmÀ1. These spectral shifts are characteristic for the
presence of hydrogen-bonded urea groups, and apparently
formation of a gel is accompanied by the formation of
intermolecular hydrogen bonds between the urea groups. The
absorptions for solid 1 (Nujol mull) are in close agreement
with these data (3343, 1632, 1561 cmÀ1, respectively), and
indicates that in the solid state hydrogen bonding also occurs.
Although 1 does not form gels in chloroform, it was found
that aggregates do build up in this solvent (vide infra). The
FT-IR spectrum of a homogeneous solution of 1 in chloroform
at low concentration shows strong absorptions for the urea
groups at 3443 (N ± H), 1667 (amide-I) and 1523 (amide-
II) cmÀ1, and corresponds very well with values reported for
N,N'-dialkylureas in the same solvent.[17] Increasing the
concentration of 1 to 47.7mm causes a shift of these
absorptions towards 3340, 1639 and 1560 cmÀ1 respectively
(Table 2). These concentration-dependent spectral shifts are
again indicative of the formation of aggregates stabilised by
intermolecular hydrogen bonds between the urea groups.[4b, 6b]
Molecular modelling: Molecular modelling is a powerful tool
to provide insight into the interaction potential surface of
molecules and into their possible modes of aggregation, but
for many known gelators the use of molecular modelling is
complicated by the large degree of conformational freedom of
the compounds. In order to reduce the conformational space
to a minimum, geminal bis-urea 7 was chosen as a model
compound for the molecular modelling experiments. The
conformational space of 7 is formed by the three dihedral
angles f1, f2 and f3 of the bonds connecting the urea moieties
and the phenyl group with the geminal carbon atom (Fig-
ure 4a). A conformational search using the CHARMm force
Figure 5. Interaction potential surface of conformer 7c.
One-dimensional aggregates of 7 can then be constructed
by applying the appropriate symmetry operations to the
various conformers: translation (P1), screw axis (P21), glide
[19]
Å
plane (Pa) or inversion (P1). When these operations are
carried out along an axis that runs through the most
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Geminal Bis-ureas
2633±2643
favourable site(s) of interaction, which can be obtained from
the interaction potential surface, one can expect that the most
stable 1D aggregates will be formed.
In general, for bis-urea molecules in which the urea groups
can be connected by any kind of linker, aggregates with
antiparallel (a-) oriented hydrogen-bonded arrays of urea
groups can be constructed by application of a translation (a-
Å
P1), glide plane (a-Pa) or inversion (a-P1) operation.
Aggregates in which the hydrogen-bonded arrays of urea
groups have a parallel (p-) orientation can be constructed by a
translation (p-P1), screw axis (p-P21) or glide plane (p-Pa)
operation (Figure 6). Evidently, a glide plane and inversion
Figure 7. Symmetry-restricted one-dimensional aggregates of 7 obtained
by molecular modelling. Energies (kcalmolÀ1) are relative to conformer 7a.
aggregates every urea group participates completely in
hydrogen bonding with an adjacent molecule.
The structures of the calculated hydrogen-bonded networks
are in general in good agreement with what is found for
various mono-urea derivatives in the solid state. For the
translational aggregates p-P1 and a-P1 the repeating distances
that give the lowest aggregate energies are 4.5 ± 4.6 Š, values
that are in excellent agreement with previously reported
X-ray data.[20] The other aggregates contain two molecules per
unit cell and give repeating distances in the range of 8.8 ±
9.0Š, which are also in good agreement with literature
reports.[6b, 20]
Figure 6. Symmetry-restricted aggregates of 7. For reasons of clarity the
hydrogen-bonding direction of the urea groups is indicated by the carbonyl
groups only.
operation can not be used when a chiral centre is present
unless one is dealing with aggregates containing both enan-
tiomers, but this restriction does not apply to our achiral
geminal bis-urea compounds.
The structures and stabilities of all these six aggregate
forms were investigated by means of molecular mechanics
calculations. Although no distinctive sites of interaction could
be obtained for conformers 7a and 7b (vide supra) it was
found that they do give stable one-dimensional aggregates, all
with an antiparallel orientation of the urea groups, whereas
the use of conformer 7c leads to aggregates with parallel-
oriented urea groups (Figure 7). The loss of the intramolec-
ular hydrogen bond in the three conformers 7a,b is compen-
sated by the formation of four intermolecular hydrogen bonds
between adjacent molecules. It was found that in all these
A distinct feature of urea compounds is that in crystal
structures the urea groups form colinear and coplanar hydro-
Å
gen-bonded arrays (Figure 8). Within the a-Pa and a-P1
aggregates, however, the hydrogen-bonded arrays deviate
substantially from colinearity and coplanarity, with a ˆ 908
Å
and b ˆ 288 for a-Pa and a ˆ 958 and b ˆ 278 for a-P1.
Therefore these aggregates are less likely to occur. In the
aggregates with a-P1, p-P1, p-P21 and p-Pa symmetry the urea
groups form indeed colinear and coplanar hydrogen-bonded
arrays. Of these aggregates, the ones with p-P21 and p-Pa
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FT-IR data. The data in Figure 9 could not be fitted by a
model which involved only the formation of dimers, and thus
suggests that higher aggregates rather than dimers are
involved.[23] This formation of higher aggregates is also
confirmed by NOESY experiments (vide infra).
1
The H NMR spectra of 1 in CDCl3 are very sensitive to
changes in temperature. Increasing the temperature for a
concentrated solution (47.7mm) of 1 causes an upfield shift of
the spectral positions of the NH protons (and a downfield shift
of the a-CH2 protons), and indicates a return to mainly
monomeric species in solution. Decreasing the temperature
causes the opposite effect, and is accompanied by line-
broadening of the spectra. Evidently, at higher concentrations
the degree of aggregation is strongly dependent on the
temperature.
À À
Figure 8. Colinearity angle a and dihedral N C O ´´´ H angle b of two
hydrogen-bonded urea fragments.
symmetry are the most stable ones, indicating that an
alternating orientation of successive molecules is more
favourable.[20, 21]
At low concentrations a change of the temperature has a
different effect (Figure 10). At 258C and a concentration of
1.6 mm the NH(e) and NH(f) signals are broad singlets but
NMR experiments: In general, NMR techniques can give a
great deal of information on, for example, self-assembly
processes in solution. Especially the use of NOESY experi-
ments may provide an insight in to how molecules are
orientated with respect to one another in an aggregated state.
It was found that the geminal bis-urea compounds do not form
gels in chloroform and are soluble up to a concentration of at
least 78.0m m, but the concentration-dependent infrared
measurements showed that these compounds nevertheless
do aggregate in this solvent (vide supra). We therefore studied
the aggregation behaviour of these compounds in chloroform
1
in more detail by using solution NMR techniques. H NMR
measurements of compound 1 in CDCl3 showed that the
spectra are extremely sensitive to changes in concentration
and temperature. Concentration-dependent measurements
revealed that at low concentrations (<0.62mm) the 1H NMR
spectrum does not change significantly, but an increase of the
concentration resulted in clear downfield shifts of the spectral
positions of the NH protons and an upfield shift of the spectral
positions of the a-CH2 protons, until at higher concentration a
plateau is reached (Figure 9). Apparently, at low concentra-
Figure 10. Temperature-dependent 1H NMR spectrum of a 1.6mm solution
of 1 in CDCl3.
when the temperature is raised to 558C, the NH(e) signal
becomes a well-resolved doublet. On the other hand, decreas-
ing the temperature results in a broadening of only the NH
signals, until at À108C they disappear, but at À308C four new
signals appear. Apparently, at À308C and lower all four NH
protons are inequivalent, indicating that rotation around f2
and f3 (Figure 4) has become slow on the NMR time scale.
These results are in excellent agreement with the molecular
modelling calculations which indicate that the minimum-
energy conformation lacks an element of symmetry and that
this conformation is stabilised by the presence of a single
intramolecular hydrogen bond. Apparently, at room temper-
ature this intramolecular hydrogen bond becomes weak
enough so that rotation around f2 and f3 becomes fast on
the NMR time scale and consequently the NH protons are
observed as two time-averaged signals.
Figure 9. Concentration-dependent 1H NMR shifts of 1 in CDCl3 at room
temperature.
Interestingly, the coupling pattern of the urea NH protons
indicates that for the monomeric species the position of the
NH(e) proton is upfield relative to the position of NH(f). This
is confirmed by 2D NOESY (vide infra) and COSY experi-
tion 1 is mainly present as a monomer, whereas at higher
concentration the equilibrium is shifted in favour of the
aggregate.[22] These results are in excellent agreement with the
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Geminal Bis-ureas
2633±2643
ments. As shown in Figure 10,
upon aggregation a large down-
field shift of NH(e) of 1.5 ppm
is observed (from 0.31 to
60.2mm in CDCl3), whereas
the other signals shift only by
0.2 ± 0.5 ppm. The high-field
position of the NH(e) signal
relative to the NH(f) signal at
low concentration and high
temperature is quite remarka-
ble and counterintuitive, since
one would have expected it the
other way round, based on sub-
stituent effects. 1H NMR ex-
periments with the model com-
pound N-benzyl-N'-octylurea
showed that in this compound
this is indeed the case. Most
likely, the anomalous upfield position of the NH(e) proton for
the monomeric species is due to shielding by the phenyl group.
This is again in excellent agreement with the results from
molecular modelling which showed that for the minimum-
energy conformation 7a one of the NH(e) protons is indeed
located in the shielding region, and apparently also compound
1 exist predominantly in the most stable intramolecular
hydrogen-bonded form both at low as well as higher temper-
atures. Since upon aggregate formation a significant confor-
mational change must take place, the NH(e) proton is no
longer to be found in the shielding region of the phenyl group,
and consequently for the aggregated species present at high
concentration the signals of the NH protons return to their
ꢁnormalꢁ spectral positions as one would have expected based
on substituent effects and the formation of hydrogen-bonded
urea species. More support for this idea comes from the data
obtained from 1H NMR spectra with [D6]DMSO as a solvent.
In [D6]DMSO no aggregation takes place and intramolecular
hydrogen bonding is also highly unlikely owing to the strongly
hydrogen-bond accepting character of [D6]DMSO, and this is
known to disrupt inter- and intramolecular solute hydrogen
bonds. In this solvent, we find for all compounds 1 ± 6 that the
signal for the NH(e) proton lies downfield with respect to the
signal for NH(f), exactly what is to be expected on the basis of
substituent effects.
Figure 11. NOESY spectrum of 1 at a concentration of 27.2mm in CDCl3.
six monomeric units.[24] Apparently, the additional NOE inter-
actions observed at high concentration correspond to inter-
molecular close contacts only present in the aggregate of 1.
On the basis of the additional NOE interactions it is evident
Å
that there must be aggregates present with P21, Pa or P1
symmetry (Figure 7), since only in these aggregates will there
be NOE interactions between protons of the phenyl and butyl
groups (Figure 12). Although on the basis of these NOESY
Figure 12. Explanation of NOE interactions between adjacent molecules
of 1.
experiments the presence of aggregates with P1 symmetry
cannot be excluded, it must be considered highly unlikely that
more than one aggregate form is present, since none of the
experiments that were carried out points towards polymor-
phism.[25]
Since the FT-IR spectroscopy results showed that hydrogen
bonding also occurs in the solid state (vide supra) H-MAS
and 13C-CP/MAS NMR experiments were carried out in order
to establish a relationship between the aggregated species in
solution (CDCl3), in the gel-state ([D8]toluene) and in the
solid state.[26]
In order to obtain more information about the structure of
these aggregates, two NOESY experiments were carried out
with 1 in CDCl3 at different temperatures and concentrations.
At 508C and a concentration of 4.0m m, the only cross peaks
observed are the ones from nearest neighbour contacts, so it
can be concluded that there is (almost) exclusively non-
aggregated 1 in solution. Increasing the concentration to
27.2mm at 258C results in a number of additional NOE cross
peaks, especially between the phenyl and butyl segments of the
molecule (Figure 11). It was observed that all NOE enhance-
ments in the aggregated state are negative, whereas they are
all positive in the nonaggregated state. This indicates that at
this concentration and temperature the majority of the
formed aggregates have a molecular weight of at least 1500
or higher, which means that these aggregates consist of at least
1
1
In general it was found that attempts to measure H NMR
spectra of gels are not successful owing to excessive dipolar
broadening, and 1H-MAS NMR of both the gel and the solid
state gave complex and highly broadened spectra, most likely
owing to dipolar interactions and spin diffusion. However, the
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J. H. van Esch, B. L. Feringa et al.
FULL PAPER
13C-CP/MAS NMR spectra are of a much better quality
(Figure 13), and give well-resolved signals for both the solid
state and the gel state, although the 13C NMR spectrum of the
latter has a poor S/N ratio, due to limited experiment time.
also occurs. In [D6]DMSO (H-bond acceptor) an upfield shift
of 1.3 ppm is observed. Doubling of the signals for the
carbonyl carbon was not observed in solution or in the solid
and gel states, suggesting that both carbonyl groups are
equivalent, although in solution there is of course a fast
exchange (vide supra). If the two carbonyls of 1 are equivalent
in the aggregate and in the gel state, then the only possible
aggregate symmetries are p-P21 and p-Pa (Figure 6, 7).
For the quaternary phenyl carbon (n) a different behaviour
is observed. It shifts from 142.8 ppm in [D6]DMSO (Fig-
ure 13a) to 139.9 ppm in CDCl3 at low concentration (Fig-
ure 13b), this results mainly from going from no intra- or
intermolecular hydrogen bond (in [D6]DMSO) to the for-
mation of an intramolecular hydrogen bond and hence to a
change of the conformation of 1. As soon as aggregation takes
place (Figure 13c and e), the signal of this quaternary carbon
atom (n) shifts downfield again. In the solid state virtually the
same position is found as in the gel state (Figure 13d).
Furthermore, upon aggregate formation in CDCl3 (Fig-
ure 13c) the signal of the geminal carbon atom (o) shows a
large line broadening. This points to a fast relaxation of this
carbon atom, probably owing to the fact that upon aggregate
formation the two urea dipoles are locked.
In general the chemical shifts in the solid state, gel state and
high concentration in CDCl3 are almost the same, and
indicates that 1 has the same conformation in these different
states. In the solid state the signals of the butyl carbon atoms
of 1 are clearly split, whereas this is not the case for the phenyl
carbon atoms. This means that in the solid state all the phenyl
groups are equivalent, but that there are two inequivalent
butyl groups present. If this splitting of butyl signals also holds
for the gel state whereas the phenyl signals do not split, then
that would be strong evidence for an aggregate with Pa-like
symmetry (Figure 6, 7), since in an aggregate with this
symmetry the two butyl groups of 1 are inequivalent. The
same is probably true in the gel state, but given the poor
quality spectra this is not a hard fact. Another reason for the
splitting of the signals may be found in the packing of the
linear aggregates in the solid state and the gel state, which
gives rise to secondary interactions that are of course not
present in solution.
Figure 13. Comparison of solution 13C NMR data (a: 61.1mm in
[D6]DMSO; b: 5.4mm in CDCl3; c: 47.7mm in CDCl3) of
1 with
13C NMR-CP/MAS data of the solid state (d) and the gel state (e).
A comparison of 1 in [D6]DMSO (Figure 13a), at low
concentration in CDCl3 (Figure 13b), at high concentration in
CDCl3 (Figure 13c), in the solid state (Figure 13d) and the gel
state in [D8]toluene (Figure 13e) reveals that the changes in
the spectral positions of the various carbon atoms are less
dramatic than for the corresponding proton spectral positions
Conclusion
1
in the H NMR spectrum.
It has been demonstrated that geminal bis-urea compounds
are effective gelators for various organic solvents, and the
concept of strong unidirectional intermolecular interactions is
very useful for the design of new organogelators. The gels
formed by these geminal bis-urea compounds have much in
common with gels from cyclic bis-urea gelators previously
reported by our group: gel formation takes place at very low
concentrations (typically less then 15mm) in a variety of
organic solvents, and is completely thermoreversible with
melting temperatures up to 1158C. Electron microscopy
showed that gel formation is due to the formation of long,
intertwined fibres with widths of 30± 300nm and lengths up to
40 mm by the bis-urea gelling agents, whereas FT-IR and
1H NMR experiments in chloroform and 1,2-dichloroethane
It is found that at both low and high concentration of 1 in
CDCl3 (Figure 13b and 13c) the carbonyl signal (p) is at about
the same position, even though at high concentration
aggregates are formed. The fact that upon aggregation the
carbonyl spectral position is shifted by not more than 0.1 ppm
can be explained by the presence of intramolecular hydrogen
bonding at low concentration, combined with additional weak
hydrogen bonding between the solvent (H-bond donor) and
the solute (both H-bond acceptor and donor). Apparently
these combined interactions have the same effect upon the
chemical shift as aggregation. In the gel and in the solid state
the same spectral positions are found for the carbonyl signal,
and indicates again that in the solid state hydrogen bonding
2640
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Chem. Eur. J. 2000, 6, No. 14

Geminal Bis-ureas
2633±2643
Preparation of geminal bis-ureas
showed that aggregation of these geminal bis-urea com-
pounds is accompanied by formation of intermolecular
hydrogen bonds between the urea groups.
1-Butyl-3-[(3-butylureido)phenylmethyl]urea (1): Benzaldehyde (2.03 g,
19.1 mmol) and n-butylurea (4.44 g, 38.2 mmol) were suspended in toluene
(125 mL). A little p-TsOH was added and the solution was refluxed for 3 h
under Dean ± Stark conditions with the exclusion of moisture from the air.
During the reaction the mixture became turbid and after cooling to room
temperature, a nontransparent, white gel was formed. The gel was filtered
with suction over a glass filter and the residue, an off-white crusty
compound, was crushed with a spatula, suspended in a 50:50 mixture of
dichloromethane and diethyl ether and subjected to ultrasound in order to
obtain a very finely divided suspension. This suspension was centrifuged
and the white sediment was collected. This procedure was repeated twice,
The relationship between molecular structure and aggre-
gation ability and structure was studied in more detail by
molecular modelling and NMR spectroscopy. Molecular
modelling revealed that these geminal bis-urea compounds
can form highly stable one-dimensional aggregates, which are
stabilised by four hydrogen bonds between urea groups of
adjacent molecules within the aggregate. Most interestingly,
the modelling experiments also indicate that for the mini-
mum-energy conformation of the monomer the urea moieties
do not have the correct orientation for the formation of stable
one-dimensional aggregates. Upon aggregation, however, a
conformational change takes place which involves rotation of
the urea moieties to a coplanar orientation, thereby exposing
all hydrogen-bonding sites along one common direction.
NMR experiments showed that such a conformational change
indeed takes place upon the formation of hydrogen-bonded
aggregates, and moreover, that the conformation in the
aggregate and the gel state is the same.
A symmetry analysis of possible one-dimensional aggregate
structures of bis-urea compounds showed that in principle a
number of aggregate structures are possible, all of which are
stabilised by the maximum number of hydrogen bonds
between adjacent molecules. The relative stabilities of the
possible aggregate structures were investigated by molecular
modelling and these studies indicate that aggregates with
either p-P21 or p-Pa symmetry are favoured over others. The
results of the NOESY NMR experiments agree well with the
molecular modelling calculations: the observed intermolecu-
lar close contacts between the phenyl and butyl moieties of
the geminal bis-urea compound unambiguously show the
presence of aggregates with either p-P21 or p-Pa symmetry,
but unfortunately, they do not exclude the presence of a
significant fraction of aggregates with P1 (translation) sym-
metry.
1
after which white solid 1 was obtained (4.72g, 13.9 mmol, 73%). H NMR
(300 MHz, [D6]DMSO): d ˆ 0.84 (t, J ˆ 7.0Hz, 6H), 1.30(m, 8H), 2.98 (dt,
J ˆ 5.9, 8.5 Hz, 4H), 6.08 (t, J ˆ 8.5 Hz, 1H), 6.15 (t, J ˆ 8.3 Hz, 2H), 6.58
(d, J ˆ 8.3 Hz, 2H), 7.21 ± 7.35 (m, 5H); 13C NMR (75.48 MHz, [D6]DMSO):
d ˆ13.7, 19.5, 32.1, 38.8, 59.2, 126.1, 127.1, 128.4, 143.0, 157.1; elemental
analysis: calcd (%) for C17H28N4O2: C 63.69, H 8.81, N 17.51; found: C
63.53, H 8.86, N 17.34; m.p.: >170oC (decomp); IR (Nujol mull): nÄmax
(cmÀ1): 3343 (s, N ± H), 1632 (s, amide-I), 1562 (s, amide-II).
1-Benzyl-3-[(3-benzylureido)phenylmethyl]urea (2): This compound was
prepared as described for 1, starting from benzylurea and benzaldehyde.
Yield 82%. White solid. 1H NMR (300 MHz, [D6]DMSO): d ˆ 4.22 (d, J ˆ
5.9 Hz, 4H), 6.25 (t, J ˆ 8.2 Hz, 1H), 6.60(t, J ˆ 9.6 Hz, 2H), 6.80(d, J ˆ
8.1 Hz, 2H), 7.19 ± 7.35 (m, 15H); 13C NMR (75.48 MHz, [D6]DMSO): d ˆ
42.8, 59.4, 125.9, 126.6, 127.0, 128.1, 128.2, 140.6, 142.7, 157.0, 182.9;
elemental analysis: calcd (%) for C23H24N4O2: C 71.13, H 6.22, N 14.41;
found: C 71.06, H 6.16, N 14.44; m.p.: >1708C (decomp); IR (Nujol mull):
nÄmax (cmÀ1): 3337 (s, N ± H), 1630(s, amide-I), 1559 (s, amide-II).
1-Butyl-3-[(3-butylureido)-(p-chlorophenyl)methyl]urea (3): This com-
pound was prepared as described for 1, starting from butylurea and p-
chlorobenzaldehyde. Yield 78%. White solid. 1H NMR (300 MHz,
[D6]DMSO): d ˆ 0.85 (t, J ˆ 7.1 Hz, 6H), 1.19 ± 1.36 (m, 8H), 2.97 (dt, J ˆ
5.9, 8.8 Hz, 4H), 6.10(brs, 3H), 6.64 (d, J ˆ 8.1 Hz), 7.30(d, J ˆ 8.4 Hz,
2H), 7.37 (d, J ˆ 8.4 Hz, 2H); 13C NMR (75.48 MHz, [D6]DMSO): d ˆ 13.7,
19.5, 32.0, 38.8, 58.7, 127.9, 127.9, 131.4, 142.0, 157.0; elemental analysis:
calcd (%) for C17H27ClN4O2: C 57.50, H 7.70, N 15.80; found: C 57.53, H
7.71, N 15.68; m.p.: >1708C (decomp); IR (Nujol mull): nÄmax (cmÀ1): 3331
(s, N ± H), 1638 (s, amide-I), 1562 (s, amide-II).
1-Butyl-3-[(3-butylureido)-(p-methoxyphenyl)methyl]urea (4): This com-
pound was prepared as described for 1, starting from butylurea and p-
methoxybenzaldehyde. Yield 65%. White solid. 1H NMR (300 MHz,
[D6]DMSO): d ˆ 0.85 (t, J ˆ 7.1 Hz, 6H), 1.22 ± 1.36 (m, 8H), 2.97 (dt, J ˆ
6.2, 9.3 Hz, 4H), 3.72 (s, 6H), 6.04 ± 6.11 (m, 3H), 6.50 (d, J ˆ 8.4 Hz, 2H),
6.87 (d, J ˆ 8.8 Hz, 2H), 7.21 (d, J ˆ 8.8 Hz, 2H); 13C NMR (75.48 MHz,
[D6]DMSO): d ˆ 13.7, 19.5, 32.1, 38.8, 55.1, 58.8, 113.4, 127.1, 134.8, 157.0,
158.3; elemental analysis: calcd (%) for C18H30N4O2: C 61.70, H 8.61, N
16.03; found: C 61.74, H 8.51, N 15.90; m.p.: >1708C (decomp); IR (Nujol
mull): nÄmax (cmÀ1): 3345 (s, N ± H), 1638 (s, amide-I), 1568 (s, amide-II).
These studies clearly show that molecular modelling and
solution NMR studies of aggregation for organic gelling
agents in combination with solid-state NMR studies can give
valuable insights into gel formation and gel structure.
Although at present polymorphism in solution aggregates
and gels of geminal bis-ureas can not be excluded, the NMR
studies point to the presence of exclusively one kind of
aggregate.[27]
1-Butyl-3-[(3-butylureido)-(p-dimethylaminophenyl)methyl]urea (5): This
compound was prepared as described for 1, starting from butylurea and p-
dimethylaminobenzaldehyde. Yield 48%. White solid. Purification of this
compound was very difficult (see elemental analysis) because of its
instability. It decomposes rapidly to the starting materials, as was noted by
the always present smell of the parent aldehyde. NMR spectroscopy reveals
that, after purification, the compound is at least of 90% purity. 1H NMR
(300 MHz, [D6]DMSO): d ˆ 0.87 (t, J ˆ 7.1 Hz, 6H), 1.27 ± 1.41 (m, 8H),
2.85 (s, 6H), 2.97 (d, J ˆ 5.5 Hz, 4H), 6.05 (brs, 3H), 6.40 (d, J ˆ 8.1 Hz,
2H), 6.67 (d, J ˆ 8.1 Hz, 2H), 7.11 (d, J ˆ 8.1 Hz, 2H); 13C NMR
(75.48 MHz, [D6]DMSO): d ˆ 13.7, 19.5, 32.1, 38.8, 40.3, 58.9, 112.1, 121.7,
130.3, 149.7, 157.0; elemental analysis: calcd (%) for C19H33N5O2: C 62.80, H
9.20, N 19.30; found: C 59.88, H 8.78, N 18.57; m.p.: >1708C (decomp); IR
(Nujol mull): nÄmax (cmÀ1): 3337 (s, N ± H), 1630(s, amide-I), 1559 (s, amide-
II).
Experimental Section
Chemicals: All compounds used (benzaldehyde, p-chlorobenzaldehyde, p-
methoxybenzaldehyde, p-nitrobenzaldehyde, dimethylaminobenzalde-
hyde, butylurea, benzylurea) were commercially available (Aldrich,
ACROS) and were used without further purification. Toluene and diethyl
ether were distilled from sodium prior to use. Dichloromethane was
distilled from P2O5 prior to use. CDCl3 (Aldrich) was dried and freed from
traces of acid over Na2SO4/K2CO3 and kept basic with some triethylamine
in order to prevent decomposition of the geminal bis-urea 1 during the
NMR experiments. [D6]DMSO (Aldrich) was used as received and stored
over molecular sieves.
1-Butyl-3-[(3-butylureido)-(p-nitrophenyl)methyl]urea (6): This com-
pound was prepared as described for 1, starting from butylurea and p-
nitrobenzaldehyde. Yield 79%. White solid. 1H NMR (300 MHz,
[D6]DMSO): d ˆ 0.85 (t, J ˆ 7.1 Hz, 6H), 1.22 ± 1.36 (m, 8H), 2.98 (dt, J ˆ
6.2, 9.3 Hz, 4H), 6.15 ± 6.22 (m, 3H), 6.82 (d, J ˆ 8.1 Hz, 2H), 7.54 (d, J ˆ
8.4 Hz, 2H), 8.20(d, J ˆ 8.4 Hz, 2H); 13C NMR (75.48 MHz, [D6]DMSO):
Chem. Eur. J. 2000, 6, No. 14
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J. H. van Esch, B. L. Feringa et al.
FULL PAPER
d ˆ 13.7, 19.5, 32.0, 38.8, 58.9, 123.2, 127.2, 146.4, 150.9, 157.0; elemental
analysis: calcd (%) for C17H27N5O4: C 55.92, H 7.39, N 19.42; found: C
55.89, H 7.24, N 19.16; m.p.: >1708C (decomp); IR (Nujol mull): nÄmax
(cmÀ1): 3352 (s, N ± H), 1640(s, amide-I), 1580(s, amide-II).
suppress additional solvent signals and allow the recording of 2D 1H ± 1H
spectra. The deuterium signal was used for locking by tuning the X-channel
on the deuterium frequency during 2D experiments.
Gelation experiments: In a typical gelation experiment a weighed amount
(ca. 10mg) of the bis-urea compound and 1 mL of the solvent were put in a
GC vial, after which the vial was tightly sealed with a thin teflon disk and a
screw cap. The vial was then heated with shaking until all the solid material
had dissolved. The solution was set aside and allowed to cool to room
temperature. Gelation was considered to have occurred when a homoge-
neous substance was obtained, which exhibited no gravitational flow.
Molecular modelling: Molecular modelling calculations were carried out
using the CHARMm 23 force field as implemented in Quanta97/
CHARMm, a product of Molecular Simulations Inc., San Diego, USA.
All calculations were carried out in the gas phase with a dielectric constant
of 1. For the non-bonding interactions a cut-off radius of 15 Š was used with
a switch function working from 11 to 14 Š. Template charges were used and
all energy terms were included, with the exception of an explicit hydrogen-
bonding term.
For the determination of melting points of the gels a steel ball (150mg) was
placed on top of a gel, after which the vial was sealed. A series of these
samples was placed in a stirred oil bath which was slowly heated (typically
2 ± 4oCminÀ1), while the positions of the steel balls were observed and the
temperature was simultaneously monitored with the aid of a thermocouple
in one of the vials. The temperature at which the steel ball had reached the
bottom of the vial was considered to be the melting point of a sample.[11]
For the calculation of interaction maps (docking experiments) one
molecule (substrate) of 7 was placed at the centre of a cube (15 Â 15 Â
15 Š3), with grid points spaced at 0.5 Š. A second molecule (probe) was
placed on a grid point and allowed to rotate with 308 increments around the
Euler angles, whereby the interaction energy with the substrate was
computed for each rotation. This procedure was repeated for each grid
point, after which the interaction map could be constructed.
For calculations of the possible 1D aggregates the crystal modelling facility
of Quanta97/CHARMm was used, with the application of periodic
boundary conditions. One conformer of 7 is placed in a tetragonal unit
Acknowledgements
This research was supported by the Stichting Technische Wetenschappen
(STW) and the Dutch Foundation for Scientific Research (NWO). The
research of Dr. J. vanEsch has been made possible in part by a fellowship of
the Royal Netherlands Academy of Sciences (KNAW). The authors also
wish to thank Ms. M. deLoos of the Stratingh Institute together with Prof.
Dr. A. Brisson and Mr. J. vanBreemen of the Biophysical Chemistry
Department for their assistance with the Electron Microscopy experiments.
ˆ
cell (a ˆ b=c) in such a way that the C O bonds of the urea groups are
more or less (anti)parallel with one of the crystallographic axes (e.g. c). Two
sides of the box are kept at a constant size of 50Š, which is much larger
than the cutoff radius for nonbonded interactions. In this way it is certain
that no interaction with neighbouring molecules is taken into account in
these directions. The third side of the box, which corresponds to the applied
symmetry operation, is kept much smaller and is systematically varied. By
doing so we only include intermolecular interaction along the c axis and
thus 1D aggregation. The chosen length of this side of the box is varied
from 4.2 ± 5.0Š when there is one molecule per unit cell (translational
symmetries p-P1 and a-P1), or from 8.4 ± 9.4 Š when there are two
molecules per unit cell (all other symmetries), thus yielding the minimum-
energy distance and optimal aggregate structure.
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it is going, NATO ASI Series, Series C: Mathematical and Physical
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281; b) J. van Esch, S. DeFeyter, R. M. Kellogg, F. DeSchryver, B. L.
Feringa, Chem. Eur. J. 1997, 3, 1238 ± 1243.
[6] a) M. de Loos, J. vanEsch, I. Stokroos, R. M. Kellogg, B. L. Feringa, J.
Am. Chem. Soc. 1997, 119, 12675 ± 12676; b) J. H. vanEsch, F. S.
Schoonbeek, M. deLoos, H. Kooijman, R. M. Kellogg, B. L. Feringa,
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Instruments: Differential scanning calorimetry (DSC) measurements were
carried out on a Perkin ± Elmer DSC7 apparatus as previously described,
and all FTIR spectra were recorded on a Matthson Instruments 4020
Galaxy series FT-IR apparatus.[6b]
Electron microscopy: For electron microscopy a piece of the gel was
deposited on a formvar/carbon coated copper grid (400 mesh) and removed
after one minute, leaving some small patches of the gel on the grid. After
drying at low pressure (<10À5 Torr) the specimen was shadowed at an angle
of 458 with platinum. The specimen was examined in a JEOL 1200 EX
transmission electron microscope operating at 80kV. In studying the
specimen, we first searched for patches of the gel to be sure that the
observed structures originate from the gel. Micrographs were taken from
structures at the periphery of the gel patches because here the fibres are
deposited in a layer thin enough to be observed by transmission electron
microscopy.
NMR experiments: Routine NMR spectra were recorded on a Varian
VXR-300 spectrometer. All other experiments were performed on a Varian
VXR-500 MHz spectrometer, with the exception of MAS-experiments,
which were carried out with a Varian Unity 400 WB NMR spectrometer
operating at 400 and 100 MHz for 1H and 13C, respectively. Chemical shifts
are denoted in d units (ppm) relative to CHCl3 (1H: d ˆ 7.27 ppm, 13C: d ˆ
77.0ppm) or DMSO ( 1H: d ˆ 2.49 ppm, 13C: d ˆ 39.5 ppm). 2D NOESY
experiments were carried out with the following parameters: spectral width
4500 Hz; 16 transients for each FID; 512 t1 increments and a 2024 Â 2024
data matrix; a mixing time tm ˆ 0.6 s was used; a p/2 shifted sine-squared
weighting function was applied prior to Fourier transformation.
For solid-state experiments, a Jakobsen-design probehead was used in
combination with a Sùrensen heating apparatus and a Varian rotor speed
control unit. The 5 mm ZrO2 spinners were spun under the magic angle
with speeds of 8.9 kHz (for solids) and at 1.8 kHz (for gels) at 308C.
13C NMR spectra were recorded after careful moulding using a recycle time
of 5 s or more and gated high power decoupling (GHPD) during
acquisition. Usually, the accumulation of 3000 ± 6000 transients resulted
in 13C spectra with appropriate signal to noise ratios. The solid state spectra
in the gel state were carried out using deuterated co-solvents in order to
[11] A. Takahashi, M. Sakai, T. Kato, Polym. J. 1980, 12, 335 ± 341.
[12] C. M. Garner, P. Terech, J.-J. Allegraud, B. Mistrot, P. Nuygen, A.
deGeyer, D. Rivera, J. Chem. Soc. Faraday Trans. 1998, 94, 2173 ±
2179.
[13] K. Murata, M Aoki, T. Suzuki, T. Harada, H. Kawabata, T. Komori, F.
Ohseto, K. Ueda, S. Shinkai, J. Am. Chem. Soc. 1994, 116, 6664 ± 6676.
[14] Evaluation of the temperature dependence of the critical aggregation
concentrations or the solubility by means of a phase-separation model
or Schraders equation is only justified when the exact solute
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Geminal Bis-ureas
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concentration at the melting temperature is known. Apparently, in this
case the melting process is not completed, and hence the solute
concentration at the melting point as determined by the dropping ball
method is not equal to the given concentration.
hydrogen bonding are most likely to be colinear (angle a, Figure 9). In
addition to that, the dihedral N ± C ± O ´´´ H angle (angle b, Figure 9) is
either (close to) 08 (24 cases) or (close to) 908 (3 cases).
[22] The same is observed for N,N'-dimethylurea, only at much higher
concentrations (0.2 ± 1.0m): K. A. Haushalter, J. Lau, J. D. Roberts, J.
Am. Chem. Soc. 1996, 118, 8891 ± 8896.
[15] a) P. Hartman, P. Bennema, J. Cryst. Growth 1980, 49, 145 ± 156; b) I.
Weissbuch, R. Popovitz-Biro, M. Lahav, L. Leiserowitz, Acta Crys-
tallogr. Sect. B 1995, 51, 115 ± 148.
[23] R. Deans, G. Cooke, V. M. Rotello, J. Org. Chem. 1997, 62, 836 ± 839.
[24] The fact that a NOE enhancement can be either positive or negative
(or even zero) has to do with the correlation time of tumbling of the
molecule or, in this case, the aggregate and hence is related to the size.
Any advanced textbook on NOE NMR spectroscopy will provide a
thorough explanation. See for example: D. Neuhaus and M. P.
Williamson, The Nuclear Overhauser Effect, VCH, Weinheim, 1989,
pp. 31 ± 39.
[25] There are bis-urea compounds that form different types of aggregates
in the same solution, but in these cases NMR experiments show
distinctive signals for the different types of aggregates: E. M. Veen, J.
vanEsch, R. M. Kellogg, B. L. Feringa, unpublished results.
[26] a) M. D. Sefcik, J. Schaefer, E. O. Stejskal, R. A. McKay, Macro-
molecules 1980, 13, 1132 ± 1137; b) H. Schönherr, P. J. A. Kenis, J. F. J.
Engbersen, S. Harkema, R. Hulst, D. N. Reinhoudt, G. J. Vancso,
Langmuir 1998, 14, 2801 ± 2809.
Â
[16] J. Cz. Dobrowolsky, M. H. Jamroz, A. P. Mazurek, Vibr. Spectrosc.
1994, 8, 53.
[17] The amide-I absorption for 1 at low concentration in chloroform
shows a quite large deviation (23 cmÀ1) from the value for 1 at low
concentration in dichloroethane. This is most likely due to the fact that
chloroform acts as a hydrogen-bond donor: a) Y. Mido, Spectrochim.
Acta 1973, 29A, 431 ± 438; b) E. I. Harnagea, P. W. Jagodzinski, Vibr.
Spectrosc. 1996, 169.
[18] Quanta97/CHARMm is a product of Molecular Simulations Inc., San
Diego, USA. Internet: http://www.msi.com.
[19] a) R. P. Scaringe, S. Perez, J. Phys. Chem. 1987, 91, 2394 ± 2403; b) J.
Perlstein, J. Am. Chem. Soc. 1994, 116, 11420± 11432; c) J. W. Lauher,
Y.-L. Chang, F. W. Fowler, Mol. Cryst. Liq. Cryst. 1992, 211, 99 ± 109.
[20] a) Y.-L. Chang, M.-A. West, F. W. Fowler, J. W. Lauher, J. Am. Chem.
Soc. 1993, 115, 5991 ± 6000; b) W. Kolodziejski, I. Wawer, K. Wozniak,
J. Klinowski, J. Phys. Chem. 1993, 97, 12147 ± 12152; c) A. J. Carr, S. J.
Melendez, S. J. Geib, A. D. Hamilton, Tetrahedron Lett. 1997, 39,
7447 ± 7450; d) C. L. Schauer, E. Matwey, F. W. Fowler, J. W. Lauher,
J. Am. Chem. Soc. 1997, 119, 10245 ± 10246; e) X. Zhao, Y.-L. Chang,
F. W. Fowler, J. W. Lauher, J. Am. Chem. Soc. 1990, 112, 6627 ± 6634.
[21] An examination of 27 crystal structures of noncyclic urea compounds
deposited in the Cambridge Crystallographic Database revealed that
the carbonyl groups of adjacent urea fragments participating in
[27] It is expected that the spectral characteristics of translational P1
aggregates are different from those of P21 and Pa aggregates.
However, highly resolved spectra are only obtained in solution, under
the conditions of fast exchange. In the solid state no exchange takes
place, but the resolution is, in these cases, drastically reduced.
Received: October 8, 1999 [F2078]
Chem. Eur. J. 2000, 6, No. 14
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