L-valine derivatised 1,3,5-benzene-tricarboxamides as building blocks for a new supramolecular organogel-like alignment medium

Article abstract of DOI:10.1002/ejoc.201801306

We were previously able to demonstrate that meso-gens self-assembled from small molecules, more specifically 1,3,5-benzene-tricarboxamides (BTAs), are capable of forming lyotropic liquid crystalline phases in chloroform and CCl₄, which are suit

Full text of DOI:10.1002/ejoc.201801306

A Journal of
Accepted Article
Title: L-Valine derivatised 1,3,5-Benzene-tricarboxamides as
Building Blocks for a new Supramolecular Organogel-like
Alignment Medium
Authors: Kevin Knoll, Martin Leyendecker, and Christina Thiele
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801306
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801306
Supported by

European Journal of Organic Chemistry
10.1002/ejoc.201801306
FULL PAPER
L-Valine derivatised 1,3,5-Benzene-tricarboxamides as
Building Blocks for a new Supramolecular Organogel-like
Alignment Medium
[
a]
[a]
[a]
Kevin Knoll, Martin Leyendecker, and Christina M. Thiele*
Abstract: We were previously able to demonstrate that mesogens
is due to the rapid, unrestricted tumbling of the molecules and
the corresponding averaging of anisotropic interactions to zero.
Thus RDCs are generally measured in lyotropic liquid crystals or
anisotropically swollen gels - collectively called alignment media
- Here, the free tumbling of the molecules is restricted by the
presence of mesogens or gel pores/cavities and therefore some
orientations are favoured over others, which results in partial
alignment. This alignment induced is ideally rather small, so that
only a small fraction of the dipolar coupling (hence called
residual dipolar coupling), approximately on the same order of
magnitude as the scalar coupling, remains and spectra thus stay
easy to interpret. This last point, specifically, is of major
importance; in fact did structure determination using dipolar
self-assembled
from
small
molecules,
more
specifically
1
,3,5-benzene-tricarboxamides (BTAs), are capable of forming
lyotropic liquid crystalline phases in chloroform and CCl
4
, which are
suitable for use as alignment media for small organic molecules. In
this context, however, it became quickly apparent that one major
limitation of such systems arises from the disruption of the self-
assembly process by certain analytes. Here, we present a modified
version of our original BTA-monomers, containing an additional
L
-valine moiety. Through this modification, the number of available
hydrogen bond acceptors/donators per monomer is doubled,
resulting in vastly increased stability. The new system thus obtained
exhibits anisotropic properties at much lower concentrations of BTA
and allows for the determination of residual dipolar couplings for
previously incompatible analytes like isopinocampheol (IPC).
Interestingly, the BTA system rather exhibits the properties of an
organogel than of a liquid crystal. This is thus the first report of the
use of an organogel based alignment medium.
[
5]
couplings, while in principle known for several decades, only
become feasible for all but the simplest molecules with the
[
6]
advent of weak aligning media in the 1990s.
From this, it is immediately apparent, that the availability of
suitable alignment media, both in relation to the induced degree
of order and compatibility with different solvents, analytes and
measurement conditions is of critical importance to the
application and further development of RDC based methods in
organic structure determination. Furthermore these media
should be easily obtainable, modifiable and allow for the highest
possible ease of sample preparation.
Introduction
In recent years the possibilities of organic structure
determination using nuclear magnetic resonance spectroscopy
Currently, the two most common groups of alignment media
used for organic compounds are lyotropic liquid crystals (LLC)
and anisotropically swollen gels. While there are few liquid
crystalline alignment media based on small molecule
(
NMR) have been much expanded thanks to ongoing and
intensive research in this field. Special attention has been paid
in this regard to the elucidation of the three-dimensional
structure of compounds. Maybe one of the most successful new
techniques in this context is the structure determination using
[7]
[8]
[9]
mesogens and peptidic LLC phases for water and MeOH,
the alignment media compatible with organic solvents thus
[
1]
residual dipolar couplings (RDCs):
Here the direct through-
[10]
usually involve either macromolecular mesogens or covalently
space interactions of two nuclear spins are utilized to obtain not
only distance, but also orientational correlations, adding to the
[11]
cross-linked polymer gels . However, to the best of our
knowledge no (low molecular weight) organogelator has been
successfully applied for this purpose yet as these are – in
[
2]
information acquired through Nuclear Overhauser Effect (NOE)
and Karplus relations.
[3]
contrast to covalently crosslinked polymer gels
– cross-
In order to obtain RDCs special experimental requirements must
be fulfilled, owing to the fact, that dipolar couplings are
linked/self-assembled via hydrogen bonds or via van der Waals
[12]
forces,
which usually do not sustain the strain needed for
[
4]
anisotropic interactions. As such they are strongly dependent
on the orientation of the spin-spin-vector in relation to the
alignment. The polymeric nature of the most-commonly applied
alignment media thus usually asks for a certain synthetic effort
external magnetic field B
0
, which makes them non-observable in
involving preparation of highly pure monomers under strictly
the isotropic solutions normally used in NMR-spectroscopy. This
[10e, 10k]
inert conditions
. Preparation of anisotropically swollen
[
11e, 11g,
gels on the other hand may involve uncommon equipment
11l]
[11c, 13]
or long equilibration times in sample preparation
.
Sample preparation times for some of the gels can be
[
a]
K. Knoll, M. Leyendecker, Prof. Dr. C. M. Thiele
Technische Universität Darmstadt,
Clemens Schöpf Institut für Organische Chemie und Biochemie,
Alarich-Weiss-Str. 4, 64287 Darmstadt, Germany.
[
11h,
significantly reduced by a compressing/ stretching-apparatus.
1
3a, 14]
Both of these groups have additionally in common, that the
alignment-) properties of the final product can depend on the
(
*
E-Mail: cthiele@thielelab.de; Homepage: www.thielelab.de
chosen polymerization and/or crosslinking conditions. This can
give rise to challenges associated with reproducibility, since
Supporting information for this article is given via a link at the end of
the document
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European Journal of Organic Chemistry
10.1002/ejoc.201801306
FULL PAPER
even small differences can impact polymer properties like chain
length or degree of crosslinking and in turn alignment
properties.
polymers are dynamic systems and therefore vulnerable to
disturbances: Other components of the sample, most
prominently the analyte can interfere with this self-assembly,
[
15]
[
16]
disrupting the alignment properties.
In our case even the
presence of the single hydrogen bond donor/acceptor in
isopinocampheol (IPC) caused a significant drop in quality of the
spectra obtained, making the extraction of RDCs impossible. It
became therefore evident, that the basic BTA structure needed
to be modified in order to increase the supramolecular stacks’
stability and in turn reduce the influence of other sample
components on self-assembly.
For this purpose we have synthesized a BTA with an additional
L-valine moiety inserted between aromatic core and the aliphatic
chain (2). Our hypothesis is, that this modification effectively
doubles the amount of possible hydrogen bonds between
monomers and thus should considerably increase the stability of
the resulting stacks. Alignment media obtained this way are
therefore expected to be much more tolerant towards analytes
or solvents capable of disrupting monomer self-assembly.
Additionally, the amino acid moiety provides easy access to a
stereogenic center, and therefore potential enantiodifferentiating
[
16]
Figure 1: The previously reported BTA monomers
sidechains (1; a: achiral, b: chiral side chain) and the modified structure with
additional -valine moieties inserted between aromatic core and aliphatic chain
2). This simple modification doubles the amount of hydrogen bond
with long aliphatic
L
(
acceptors/donators and thus allows for stronger interactions between
monomers.
[
24]
properties. As several groups
have demonstrated, the
An answer to these polymer-related challenges might be the use
of non-polymeric alignment media build from small molecules.
In this context we were recently able to demonstrate that
mesogens self-assembled from small molecules using non
covalent interactions, so called supramolecular polymers, can be
used to obtain suitable alignment media in organic solvents as
supramolecular interactions of such amino acid containing BTAs
can also be easily tuned by the choice of amino acid and should
thus facilitate further customizations in the future. In the
following we thus investigate the alignment properties of the
[
7]
L-valine-modified benzene-tricarboxamide obtained.
[
16]
well.
For this purpose we have utilized benzene-
tricarboxamides (BTAs, Fig. 1), known to self-assemble into
long helical stacks by threefold hydrogen bonding in solution.
[
17]
Results and Discussion
These aggregates can then in turn act as mesogens essentially
analogous to the polymer helices in conventionally used
polymer-based alignment media. Additionally it is possible to
obtain chiral BTA stacks and control the handedness of the
Synthesis
The desired tris-L-valine-n-octadecyl-BTA was synthesized using
a three step sequence starting form 1,3,5-benzene-tricarboxylic
[
17b]
supramolecular helix
by adding a stereocenter to the
acid (3, Scheme 1), using carbonyldiimidazole (CDI) as coupling
substituents and thus causing one helix sense to be
[
25]
[
18]
[19]
reagent. An intermediate protection of the amino acid moiety
as ester is required to avoid oligomerization reactions during the
first step. We have chosen this CDI based coupling method over
the, especially in regards to BTAs, more commonly used
energetically
favoured over the other.
Due to
diastereomorphous interactions between chiral mesogens and
chiral analyte, leading to different orientations of the latter
[
10b]
depending on configuration,
such a chiral alignment medium
[
22b, 26]
route
utilizing carboxylic acid chlorides in order to avoid a
enables discrimination of enantiomers based on anisotropic
[
10c, 10d, 10j]
[16]
possible racemization of the amino acid , which is expected to
occur when such rather harsh reaction conditions are used.
Using this sequence the -valine-methyl-ester-BTA (4) was
obtained in 72.7 %, the BTA-amino acid (5) in 83.0 % and finally
the target compound (2) in 28.9 % yield, respectively. For the
last step it is of great importance to use a substoichiometric
amount of CDI and to make sure that all of it has reacted prior to
NMR observables.
As we were able to demonstrate,
[
25]
this principle remains operative even if just a small amount of
L
chiral BTA (1b) is added to the bulk of achiral BTAs (1a,
[
20]
sergeant-and-soldier-principle ).
In addition to the aforementioned lyotropic liquid crystalline
phases, there have also been reported some cases, in which
[
21]
[22]
BTAs form hydro-
and organogels,
either by polymer-
1
[
22b, 23]
adding the amine (e.g. through H NMR). Otherwise a side
analogous coiling of long aggregates
and/or extensive
[
22a]
product (a substituted urea) would form (presumably) from the
reaction of surplus CDI with some of the amine, which we found
to be essentially inseparable from 2. The final product is a white
cross-linking
between monomers.
A large advantage of such supramolecular systems lies not only
in the much easier preparation and purification of the monomers
required, but also in the absence of a preceding polymerization
step, avoiding the influence of aforementioned polymer-specific
factors. A considerable limitation of our previously reported
systems stems, however, from the fact that supramolecular
(if very pure) to off-white solid, essentially insoluble in most polar
solvents (except for trifluoroacetic acid) and very sparsely
soluble in non-polar solvents. This made purification challenging,
but we found a solid-liquid extraction using 2-propanol as the
liquid phase to be quite effective.
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European Journal of Organic Chemistry
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Scheme 1: Three step synthesis of the tris-L-valine-n-octadecyl-BTA (2) from 1,3,5-benzene-tricarboxylic acid: 1,3,5-benzene-tricarboxylic acid (3) is coupled with
L-valine methyl ester using CDI. The resulting BTA-valine methyl ester (4) is then deprotected by saponification and the BTA-amino acid (5) obtained
subsequently coupled utilizing CDI once again, this time with n-octadecylamine, forming the target BTA (2). This reaction sequence should, in theory, allow for the
synthesis of similar BTAs containing different amino acids as well.
General Properties of Phases
-
Finally we did also oberserve some effect of the purity of the
Before describing our new system´s interactions with selected
analytes it is necessary to first discuss some general properties,
as there are a number of major differences compared to our
original systems.
used deuterated solvent, with freshly destilled CDCl (acid and
water free) yielding best results in terms of solvent signal
quadrupolar splittings.
3
For the previously described, purely alkyl substituted BTAs,
sample preparation consists simply of homogeneously
dissolving the BTA monomers in the solvent by heating. This
method was, however, rather unsuccessful for our new system
and yielded mostly isotropic samples or if anisotropy was
observed at all it was badly reproducible. Further investigation
Based on these findings we were able to devise an optimized
preparation procedure: The phase components are mixed by
gentle shaking, then directly placed in the pre-heated
spectrometer (320 K) while the mixture is still fluid and kept
inside the field until the solvent signal quadrupolar splitting is
stable (approx.
3 h). Phases thus obtained appear as
(
for more details see SI section 2) then revealed a number of
homogenous, slightly turbid gels. Surprisingly, there was no
observable birerefringence between crossed polarizers.
factors impacting phase behaviour decisively. These, were not
observed for the original system:
The approximate concentration range for anisotropic behaviour
in deuterated chloroform lies between 0.7 and 4.0 percent (w/w),
which is a significant improvement over the original system with
-
High temperature and centrifugation seem to heavily disrupt
[
16a]
aggregation. This is clearly demonstrated by the fact, that even
previously anisotropic samples became irreversibly isotropic
upon centrifugation or heating close to boiling point of the
solvent. (This allows to obtain both isotropic and anisoptropic
couplings from the same sample, see SI sections 2 and 6.5)
26 to 33 percent (w/w) . Even higher concentrations than that
may be possible, but mixing the phase components becomes
increasingly difficult above 4 percent w/w), because of their high
viscosity, leading to highly inhomogeneous phases unsuitable
for determination of RDCs. Also, our new system does not seem
to possess a lower critical concentration, at which it starts to
become partly isotropic. Instead it steadily progresses towards
lower solvent signal quadrupolar splittings with decreasing
-
Magnetic fields appear to play a major role: Samples prepared
without the presence of the spectrometer´s B
isotropic in all cases.
0
field stayed
concentration, eventually reaching
a point, at which the
2
individual branches of the H signal are no longer distinguishable.
With values of up to 200 Hz the solvent signal quadrupolar
splittings of our new system are significantly lower than for the
purely alkyl substituted BTAs (>1000 Hz). Still, taking into
account the vast differences in solubility, this might just reflect
the difference in monomer concentration.
-
The viscosity of the sample at the time of entering the magnetic
field is another point of critical importance. While all samples
prepared formed a solid gel after some time, those which had
already partly congealed exhibited drastically reduced H solvent
signal quadrupolar splittings (as indicator of anisotropy and
strength thereof) or were even isotropic.
2
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European Journal of Organic Chemistry
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The in some cases significant differences between our original,
purely alkyl substituted and the new, amino-alkyl substituted
BTA, especially in regards to the successful preparation of
anisotropic samples, certainly urge the question, in how far the
valine moiety changes the self-assembly process. In fact,
considering the apparent lack of typical liquid crystalline
on BTA self-assembly we found to be minimal in our previous
work.
[
16]
properties (fluidity, birefringence) and of
a lower critical
concentration typically observed for liquid crystalline alignment
media, it must be questioned, whether our new system is a liquid
crystal at all. Actually, it seems to have far more in common with
a gel. It would then, however, differ significantly from other
(
covalently cross-linked) gel based alignment media, for which
external strain is required to induce anisotropic properties.
Returning to the question regarding what causes this transition
from lyotropic liquid crystal to gel, the most obvious explanation
is the additional set of hydrogen bond donators/acceptors
present in our new monomer. While this was intended to
predominantly enhance the supramolecular stacks´ stability, it of
course also allows for cross-linking between monomers or
aggregates. Compared to the set of hydrogen bond
donators/acceptors at the BTA core, the outer set of hydrogen
bond donators/ acceptors has much more degrees of freedom.
This probably promotes cross-linking. The sensibility of our
system to heating and centrifugation is then likely caused by the
destruction of already present aggregates, followed by cross-
linking of the liberated monomers/oligomers. The result is a
heavily cross-linked state, from which the system cannot recover,
because doing so would require an extensive micro-scale
reorganisation. Still, some moderate heating seems to be
beneficial, possibly because this allows for faster reorientation of
stacks and/or promotes certain self-assembly processes
Figure 2: Extracted one-bond C-H-RDCs for samples "K" with (-)- and
"O" with (+)-β-pinene, containing 4.0% BTA 2 (w/w, see SI section 3.2 for
exact sample compositions). Solvent signal quadrupolar splittings:
(
Q
∆ (300/320 K) = 129.88/125.55 Hz ("K"), 129.47/125.38 Hz ("O")).
Since all samples became gels after some time, the
aformentioned cross-linking can apparently not be suppressed
completely. That we are able to obtain anisotropic phases at all,
is then probably owed to the orientation of preformed stacks
being faster than cross-linking. If these small aggregates are
subjected to a strong directing force, in our case a magnetic field,
the resulting gel then contains small, uniformly oriented,
anisotropic cavities, which in turn allow for alignment of analytes.
Such an interaction between the aggregates and the magnetic
field is plausible, as BTA stacks are known to possess a macro
Samples with β-pinene exhibit very similar solvent signal
quadrupolar splittings to those prepared without any analyte.
While the RDCs observed (Fig. 2B) amount only to a few Hz,
[
29]
probably due to the relatively small alignment strength, fits
performed using these datasets yielded very good Q-factors
[
30]
for
both
temperatures.
There
seems
to
be
no
enantiodifferentiation present, however, as RDCs for the
different enantiomers are essentially identical within the
estimated error. This is in contrast to our original, purely alkyl-
substituted BTAs, in which a stereogenic center, even within a
small fraction of monomers used, was able to make enantiomers
distinguishable.
[
27]
dipole moment along the stack axis
and orientation in a
magnetic field has previoisly been reported for different
[
28]
supramolecular systems other than BTAs.
Experiments with an analyte lacking hydrogen bond
acceptors/donators: β-pinene
Experiments with an analyte containing hydrogen bond
acceptors/donators: Isopinocampheol
Before adding an analyte potentially capable of disrupting BTA-
self-assembly to our system, we have first performed tests with
two enantiomers of an analyte devoid of hydrogen bond
acceptors/donators at two different temperatures (300 K and
With our original, purely alkyl-substituted BTAs it was difficult to
obtain stable, anisotropic phases, when isopinocampheol (IPC,
Fig. 3), an analyte containing just a single hydroxy group was
3
20 K). This was done both in order to investigate general phase
[
16]
added. Since such a group can act both as a hydrogen bond
acceptor and donor, it is expected to be able to disrupt proper
self-assembly of the stacks. After the promising results with β-
pinene we therefore repeated the experiments described in the
previous section with IPC as analyte.
properties like stability, alignment strength and
enantiodifferentiation without interferences and to provide a
point of reference in terms of relative stability. The analyte
chosen for this purpose was β-pinene (Fig. 2), whose influence
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European Journal of Organic Chemistry
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The effects of adding IPC to our new system were very limited
and did not significantly differ from those obtained with β-pinene.
While sample components formed a gel slightly faster, probably
because the additional functional group on the analyte promotes
cross-linking to some degree, this poses no problem if the
samples are properly prepared. Changes in the solvent signal
quadrupolar splittings observed in comparison to the pure phase
here again amounted to just a few Hz and spectral quality was
still good at 320 K, even though lines were broader and line
shape distortions appeared. At 300 K, on the other hand,
distortions and line broadening became very pronounced for
some signals, making extraction very difficult from CLIP-
[
31]
[32]
HSQCs
and necessitating the use of F1 coupled HSQC
spectra for determination. Surprisingly, we found the average
size of the RDCs obtained to be more than an order of
magnitude larger than for β-pinene, which could also be an
explanation for the observed reduction in spectral quality.
Nevertheless, this is a stunning observation, as it could mean,
that the size of observable RDCs is, at least for such BTA based
systems, heavily dependent and therefore tuneable by specific
monomer-analyte interactions.
We were able to extract all C-H-couplings (Fig. 3) from our
spectra measured at 320 K and most from those measured at
3
00 K. The missing RDCs (C4-H4s and C5-H5) were
unobtainable due to strong signal distortions, likely due to too
strong alignment. Accordingly distortions decreased
substantially at even slightly reduced BTA concentrations (3.5%
"S") vs. 4.0%, both w/w; see SI section 3.2) and the
Figure 3: Extracted one-bond C-H-RDCs for samples "P" with (-)- and
"
D" with (+)-IPC, containing 4.0 % BTA 2 (w/w, see SI section 3.2 for exact
sample compositions). Values (RDC and errors) for sample “P” were scaled up
2
according to the difference in solvent signal H quadrupolar splitting for
(
comparison (∆
("P")).
Q
(300/320 K) = 128.23/126.51 Hz ("D"), 121.85/114.29 Hz
aforementioned couplings became extractable even at 300 K.
Fits performed with these RDC datasets as before yield
excellent Q-factors, again with better results for the 320 K
measurements. Regardless of the greater size of the RDCs,
however, the differences in couplings between enantiomers
were still small. Only a few are greater than the estimated range
of error. It is therefore not possible to answer the question
regarding enantiodifferentiation at this point; still, even if there
was such an effect, it seems to be very limited in our system. A
possible explanation for this lack of enantiodifferentiating
properties could be the gel-like nature of our system, which most
likely is accompanied by a more complex micro structure,
deviating from the ideal 6-fold hydrogen bonding. In such a
situation, the stereogenic information of the stereogenic centre
of the amino acid might not be properly translated into a
Conclusions
We were able to demonstrate that the stability of BTA-based
supramolecular alignment media against self-assembly
disrupting analytes can be decisively improved by increasing the
amount of hydrogen bond donors/ acceptors via the addition of
an
L-valine moiety. While this addition apparently leads to
unwanted cross-linking between monomers, proper sample
preparation can minimize the impact of these interactions. The
spectrum of compatible analytes for these systems is therefore
vastly increased. In tandem with our observation that alignment
strength for a given analyte is apparently depending on specific
monomer-analyte interactions, this could in future allow to tailor
preferred helical sense. Furthermore the long alkyl chains (C18
)
could shield the stacks´ centre too much and thus prohibit the
proper interaction necessary for enantiodiscrimination. In order
to check for the latter we have also synthesised the n-dodecyl-
analogue of BTA 2 - While this compound also formed gels,
none of them demonstrated anisotropic behaviour, however.
3
BTA-based alignment media in CDCl . Probably the only
setback is the apparent loss of enantiodifferentiating properties
compared to our originally published sergeant-and-soldier
systems. As this is, however, likely caused by the additional set
of hydrogen bond acceptors changing the way stacks are
formed from the simple three-fold helical stacking mode to a
more complex one, suitable changes to the BTA structure might
be able to amend this as well.
While a determination of the exact phase morphology is certainly
beyond the scope of this work, we can at least attest, that our
new system shares more characteristics with a gel than it does
with a liquid crystal. If it should indeed prove to belong in the
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European Journal of Organic Chemistry
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former group, this would represent an entirely new class of
amorphous supramolecular organogel-based alignment media.
by filtration and dried thoroughly in vacuo. Yield: 1.62 g of a yellowish
solid (3.19 mmol, 83.0 %). This is essentially the general procedure
[34]
proposed by Theodorou et al. . This compound has previously been
[22b]
prepared by Ishioka et al.
Experimental Section
Synthesis of
1
3
5
N ,N ,N -tris-[L-Val-OMe]-benzene-1,3,5-tricarboxamide (4)
In a flask flushed with argon 1.11 g trimesic acid (5.28 mmol, 1 eq.) were
dissolved in 100 ml of dry THF. This solution was then cooled to 0 °C,
2
.67 g CDI (16.47 mmol, 3.1 eq.) were added slowly and the resulting
mixture stirred for 24 h at room temperature. Next, the mixture was
cooled to 0 °C again, 2.92 g L-valine methyl ester hydrochloride (17.42
mmol, 3.3 eq.) and 2.6 ml triethylamine (1.89 g, 18.71, 3.5 eq.) added
and the stirring continued for another 24 h at room temperature. Finally,
the solvent was removed in vacuo and the residue recrystallized from 2-
propanol, yielding 2.11 g (3.84 mmol, 72.7 %) of a white, voluminous
1
6
H NMR (500 MHz, DMSO-d , 300K, ref.: DMSO = 2.5 ppm): δ = 12.67
[33]
solid. This is in principle the procedure used by Gelinsky et al.
to
7
4
1
5
(
(
s, 3H ), 8.74 (d, J = 8.2 Hz, 3H ), 8.40 (s, 3H ), 4.33 (m, 3H ), 2.21
pseudo sx [expected: dqq], J = 6.8 Hz, 3H ), 0.99 (pseudo-t [expected:
obtain substituted BTAs. This compound has previously been prepared
8
[22b]
by Ishioka et al.
9a+b
2
*d], J = 6.1 Hz, 18H ) ppm.
1
3
6
C NMR (126 MHz, DMSO-d , 300K, ref.: DMSO = 39.51 ppm):
6
3
2
1
5
δ = 172.98 (C ), 166.42 (C ), 134.52 (C ), 129.56 (C ), 58.56 (C ), 29.58
8
9a
9b
(
C ), 19.35 (C ), 18.82 (C ) ppm.
MS (ESI, DMSO): expected: 508.23 m/z; found: 508.23 m/z, 586.25 m/z
M+DMSO).
(
IR (pure solid, characteristic bands): N-H = 3226.33 (valence), Ar-H
057.23 (valence), -CH3 = 2966.57 (valence), C=O = 1716.18 (valence,
acid), C=O = 1634.22 (valence, amide), N-H = 1546.29 (deformation)
=
3
-
1
cm .
1
3 3
H NMR (500 MHz, CDCl , 300 K, ref.: CDCl = 7.24 ppm): δ = 8.38 (s,
1
4
5
3
9
H ), 6.97 (d, J = 8.6 Hz, 3H ), 4.76 (dd, J = 8.6, 5.3 Hz, 3H ), 3.78 (s,
Synthesis of
7
8
9a
1
3
5
H ), 2.27 (m [expected: dqq], 3H ), 1.01 (d, 4.0 Hz, 9H ), 0.99 (d, 4.0
N ,N ,N -tris-[L-Val-n-octadecyl]-benzene-1,3,5-tricarboxamide
(2, BTA-Val-C18
9b
Hz, 9H ) ppm.
)
1
3
C NMR (126 MHz, CDCl
3
, 300 K, ref.: CDCl
3
= 77.21 ppm): δ = 172.52
In a flask flushed with argon 806.00 mg of the N1,N3,N5-tris-[L-Val-OH]-
1,3,5-benzene-tricarboxamide 5 (1.59 mmol, 1 eq.) were suspended in
70 ml of dry THF. This suspension was then cooled to 0 °C, 757 mg of
CDI (4.67 mmol, 2.9 eq.) were added and the resulting mixture stirred for
6
3
2
1
5
7
(
(
C ), 165.75 (C ), 135.08 (C ), 128.85 (C ), 58.16 (C ), 52.58 (C ), 31.72
C ), 19.28 (C ), 18.35 (C ) ppm.
8
9a
9b
2
1
4 h at room temperature. Afterwards it was once again cooled to 0 °C,
.465 g n-octadecylamine (5.44 mmol, 3.4 eq.) dissolved in 60 ml of dry
MS (ESI): expected: 550.28 m/z; found: 550.28 m/z.
THF were added slowly via dropping funnel and then stirred for another
4 h at room temperature. The resulting solid was collected by filtration,
IR (pure solid, characteristic bands): N-H = 3222.13 (valence), Ar-H
=
2
3
056.08 (valence), -CH3 = 2958.53 (valence), C=O = 1754.31 (valence,
washed with small portions of THF and 2-propanol, sequentially, and
then dried. Purification of this dry raw product was performed by
suspending it in approx. 400 ml of 2-propanol, breaking down particles to
a uniform size with a low power ultrasonic bath and decanting the
homogeneous suspension from remaining larger particles. This
suspension was then filtrated again (requires frit with small pore size, min.
Por. 3), washed with 2-propanol and the obtained residue dried
thoroughly to yield 574.90 mg of a white solid (0.46 mmol, 28.9 %). This
ester), C=O = 1640.92 (valence, amide), N-H = 1551.84 (deformation)
-
1
cm .
Synthesis of
1
3
5
N ,N ,N -tris[L-Val-OH]benzene-1,3,5-tricarboxamide (5)
To a suspension of 2.11 g of the N1,N3,N5-tris-[L-Val-OMe]-benzene-
[33]
1
7
,3,5-tricarboxamide (3.84 mmol, 1 eq.) in 200 ml of THF were added
68 mg of sodium hydroxide (19.20 mmol, 5 eq.) dissolved in 100 ml
is in principle the procedure used by Gelinsky et al.
substituted BTAs.
to obtain
methanol and 50 ml deionised water and the resulting mixture then
stirred at room temperature for 24 h. The suspension obtained was
brought close to neutral with 1N HCl (approx. 90% of the theoretical
amount) and the solvents were subsequently removed in vacuo. This
residue was then dissolved in 50 ml of deionised water and acidified with
1
N HCl (pH = 2) causing a white solid to precipitate, which was collected
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European Journal of Organic Chemistry
10.1002/ejoc.201801306
FULL PAPER
part of 14-20
9b
13
11
[
2
29.10, 29.09, 28.99, 28.88, 28.86] (C
6.2 (C ), 22.0 (C ), 17.63 (C ), 17.49 (C ), 12.36 (C ).
), 28.54 (C ), 27.9 (C ),
12
18
9a
21
MS (MALDI):
expected: 1008.8 u/z;
found:
1031.8 u/z (M+Na).
see SI section 1.3 for isotope pattern.
IR (pure solid, characteristic bands): N-H = 3281.28 (valence), -CH2
=
2
920.76 (valence), -CH2 = 2851.77 (valence), C=O = 1634.53 (valence,
-
1
amide), N-H = 1532.11 (deformation), -CH2 = 1466.31 (deformation) cm .
1
0
H NMR (700 MHz, TFA-d , 300K, ref.: TFA = 11.50 ppm): δ = 8.72 (s,
1
4
7
5
3
6
-
H ), 8.33 (m, 3H ), 7.96 (br s [expected: t], 3H ), 4.44 (m, 3H ), 3.42 (m,
Acknowledgements
1
0
8
11
12
13
H
), 2.32 (m, 3H ), 1.59 (m, 6H ), 1.31 (m, 6H ), 1.29 (m, 6H ), 1.24
1
4-26
9a
9b
1.12 (br m, 78H
), 1.08 (d, 6.6 Hz, 9H ), 1.05 (d, 6.6 Hz, 9H ), 0.77
27
The authors would like to thank the Deutsche
(
t, 9H ) ppm.
Forschungsgemeinschaft
(DFG)
for
funding
(grant
1
3
TH 1115/11-1) and Volker Schmidts for assistance and
helpful discussion regarding the calculation of tensors using
0
C NMR (175 MHz, TFA-d , 300K, obtained from HSQC and HMBC):
6
3
2
1
5
10
δ = 174.7 (C ), 169.6 (C ), 133.29 (C ), 131.63 (C ), 62.3 (C ), 42.0 (C ),
3
2
part of 14-26
8
part of 14-26
), 28.92 (C ), 28.23 (C ), the software RDC@hotFCHT. We thank Leon Bleichrodt for
9a 9b 27
13
11
1.90 (C
6.52 (C ), 23.32 (C
), 30.52 (C ), 29.40 (C
12
part of 14-26
), 17.99 (C ), 17.86 (C ), 12.70 (C ) ppm.
help with the synthesis of Val-BTA-C12
.
MS (MALDI):
expected: 1261 u/z;
found: 1284 u/z (M+Na), 1300 u/z (M+K).
see SI section 1.2 for isotope pattern.
Keywords: Benzene-tricarboxamides • Alignment Media •
Residual Dipolar Couplings • NMR-Spectroscopy • Self
Assembly
IR (pure solid, characteristic bands): N-H = 3283.44 (valence), -CH2
=
2
916.87 (valence), -CH2 = 2849.18 (valence), C=O = 1637.43 (valence,
-
1
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3
5
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European Journal of Organic Chemistry
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European Journal of Organic Chemistry
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Entry for the Table of Contents (Please choose one layout)
FULL PAPER
We present a modified version of our
original BTA-monomers, containing
Alignment Media, Supramolecular
Polymers
an additional L-valine moiety.
Kevin Knoll, Martin Leyendecker, and
Christina M. Thiele*
Through this modification, the
number of available hydrogen bond
acceptors/donators per monomer is
doubled, resulting in vastly increased
stability. The new system thus
obtained exhibits anisotropic
properties at much lower
Page No. – Page No.
L-Valine derivatised 1,3,5-Benzene-
tricarboxamides as Building Blocks
for a new Supramolecular
concentrations of BTA and allows for
the determination of residual dipolar
couplings for previously incompatible
analytes.
Organogel-like Alignment Medium
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