Asymmetrically substituted benzene-1,3,5-tricarboxamides: Self-assembly and odd-even effects in the solid state and in dilute solution

Article abstract of DOI:10.1002/chem.200802196

Asymmetric benzene-1,3,5-tricarboxamides (aBTAs) comprising two n-octyl and one chiral methylalkyl side chain were synthesised and characterised. The influence of the position and the configuration of the chiral methyl group (methyl at the α, β or y posit

Full text of DOI:10.1002/chem.200802196

FULL PAPER
DOI: 10.1002/chem.200802196
Asymmetrically Substituted Benzene-1,3,5-tricarboxamides: Self-Assembly
and Odd–Even Effects in the Solid State and in Dilute Solution
Patrick J. M. Stals, Maarten M. J. Smulders, Rafael Martꢀn-Rapffln,
Anja R. A. Palmans,* and E. W. Meijer*[a]
Abstract: Asymmetric benzene-1,3,5-
tricarboxamides (aBTAs) comprising
two n-octyl and one chiral methyl–
alkyl side chain were synthesised and
characterised. The influence of the po-
sition and the configuration of the
chiral methyl group (methyl at the a, b
or g position) in the aliphatic side
chains on the liquid-crystalline proper-
ties and the aggregation behaviour of
the aBTAs was systematically studied
and compared to symmetrical benzene-
1,3,5-tricarboxamides (sBTAs). Solid-
state characterisation (polarised optical
microscopy, IR spectroscopy, X-ray dif-
fraction and differential scanning calo-
rimetry) revealed that all aBTAs show
threefold, a-helical-type intermolecular
hydrogen bonding between neighbour-
ing molecules and exhibit a columnar
hexagonal organisation from room
temperature to well above 2008C.
Moving the chiral methyl group closer
to the amide group stabilises the
liquid-crystalline state, as evidenced by
a higher clearing temperature and cor-
responding enthalpy. The self-assembly
of dilute solutions of the aBTAs in
Cotton effect demonstrated a pro-
nounced odd–even effect, whereas the
value of the molar ellipticity, De, in the
aBTAs was independent of the position
of the methyl group. Subsequent tem-
perature-dependent CD measurements
showed that the aggregation of all
aBTAs can quantitatively be described
by the nucleation-growth model and
that the stability of the aggregates in-
creases when the chiral methyl group is
closer to the amide moiety. The results
presented herein illustrate that even
small changes in the molecular struc-
ture of substituted benzene-1,3,5-tri-
carboxamides affect their solid-state
properties and their self-assembly be-
haviour in dilute solutions.
methylcyclohexane
was investigated with circular dichro-
ism (CD) spectroscopy. The sign of the
(ꢀ10ꢁ5 molLꢁ1)
Keywords: chirality
·
circular
dichroism · liquid crystals · self-
assembly · synthesis design
Introduction
(Figure 1). BTA-based compounds have been studied in
detail as organogelators,[2] liquid crystals,[3] nucleating agents
for isotactic polypropylene[4] and nanostructured materials.[5]
These rather simple molecules self-assemble into long, heli-
cal columnar aggregates due to threefold a-helical-type in-
termolecular hydrogen bonding and p–p stacking. The helic-
ity in the columns was unequivocally observed in the solid
state by crystal structure elucidation (Figure 1).[6] In dilute
apolar solutions, strong Cotton effects were observed when
a chiral centre was introduced into the alkyl side chains,
showing that the helical structure remains intact upon dilu-
tion.[7]
To date, studies relating to the self-assembly of alkyl-sub-
stituted BTAs in dilute alkane solutions focussed predomi-
nantly on symmetrical derivatives comprising three chiral
(R)- or (S)-3,7-dimethyloctyl side chains (sBTA-R/S-3Me,
Scheme 1) or three achiral n-octyl side chains (sBTA-C8,
Scheme 1).[7] A disadvantage of using symmetrical BTAs is
that diastereomers are formed when the chiral side chain is
not optically pure, which complicates the interpretation of
Self-assembly has attracted considerable interest in the field
of (macro)organic chemistry because it allows for the forma-
tion of complex, dynamic systems starting from relatively
simple building blocks.[1] In this respect, benzene-1,3,5-tricar-
boxamides (BTAs) represent a particularly interesting class
of compounds because they show well-defined aggregates in
the solid state, and in concentrated and dilute solutions
[a] P. J. M. Stals, M. M. J. Smulders, Dr. R. Martꢀn-Rapffln,
Dr. A. R. A. Palmans, Prof. Dr. E. W. Meijer
Laboratory of Macromolecular and Organic Chemistry and Institute
for Complex Molecular Systems
Eindhoven University of Technology, PO Box 513
5600 MB Eindhoven (The Netherlands)
Fax : (+31)402-451-036
E-mail: A.Palmans@tue.nl
E.W.Meijer@tue.nl
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200802196.
Chem. Eur. J. 2009, 15, 2071 – 2080
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dition, the solubility of symmetrically a- and b-methyl-sub-
stituted derivatives is poor in alkane solvents.[8]
For these reasons, we decided to continue our studies to
elucidate the self-assembly of BTAs with asymmetrically
substituted BTAs (aBTAs) comprising two achiral, n-octyl
chains and one chiral chain. Apart from avoiding diastereo-
meric mixtures, such derivatives allow the systematic study
of the effect of changing the configuration and position of
one methyl group on the side chain on the solid-state prop-
erties and self-assembly behaviour in dilute solutions. In
view of odd–even effects observed in (chiral) nematic liquid
crystals,[9] helical polymers[10] and helical aggregates of oligo-
and polythiophenes,[11] we anticipated that odd–even effects
may also be operative in these aBTAs. Typically, the odd–
even effect is ascribed to the alteration of the spatial posi-
tion of a chiral group when moving down an aliphatic chain,
which is reflected in the clearing temperatures in nematic
liquid crystals, helical pitches in cholesteric mesophases and
chiroptical properties of helical polymers and aggregates.
For example, when changing the position of a methyl group
from the a to the b and g position along the alkyl chain in
helical polyisocyanides and maintaining the same configura-
tion, alternating signs of the Cotton effects were ob-
served.[12]
Figure 1. Different aggregation states of BTAs as function of concentra-
tion (top) and the helical packing of a BTA derivative in the solid state
(bottom).
We herein show the synthesis
and characterisation of a new
family of aBTAs comprising
two n-octyl chains. In the third,
chiral side chain, we vary the
configuration (R and S) and the
position of the methyl group
from the a position to the g po-
sition (Scheme 1). Characterisa-
tion of the aBTAs in the solid
state was conducted with infra-
red (IR) spectroscopy, differen-
tial
scanning
calorimetry
(DSC), polarised optical micro-
scopy (POM) and X-ray diffrac-
tion. Two symmetrically substi-
tuted reference compounds,
[2a]
sBTA-CH3
and sBTA-me-
thoxyethyl,[6a] were included in
this study because their crystal
structures have previously been
elucidated. For comparison, we
remeasured the solid-state data
for selected symmetrically sub-
stituted BTAs (sBTAs, sBTA-
C8 and sBTA-R/S-3Me) under
identical conditions. In addi-
tion, the self-assembly behav-
iour in dilute alkane solutions
of aBTAs was studied by circu-
Scheme 1. Chemical structure of symmetric and asymmetric benzene-1,3,5-tricarboxamides (sBTA and aBTA,
respectively).
the data. As Hanabusa et al. recently showed, the solution
behaviour of rac-3,7-dimethyloctyl-substituted BTAs differs
significantly from the optically enriched derivatives.[2g] In ad-
lar dichroism (CD) spectroscopy to assess the presence of
an odd–even effect. CD spectroscopy was recently found to
be a powerful tool in elucidating the nature of the self-as-
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Asymmetrically Substituted Benzene-1,3,5-tricarboxamides
FULL PAPER
Table 1. Relevant IR vibrations for sBTAs and aBTAs.[a]
sembly process in sBTAs.[7b] Finally, temperature-dependent
CD measurements were conducted to investigate self-assem-
bly of the aggregates formed and their stability.
ꢁ
Entry
Compound
n
R
n
G
nACHTUNGTRENNUNG
A
A
]
A
]
1
2
3
4
5
6
7
8
sBTA-methoxyethyl
sBTA-CH3
3250
3333/3259
3236
3306
3223
3234
3235
3240
3240
1635
1641
1640
1644
1637
1634
1635
1638
1637
1636
1639
1551
1539
1557
1531
1564
1556
1556
1556
1557
1558
1563
sBTA-C8H17
sBTA-C8H17
Results
[b]
sBTA-S-3Me
aBTA-R-1Me
aBTA-S-1Me
aBTA-R-2Me
aBTA-S-2Me
aBTA-R-3Me
aBTA-S-3Me
Synthesis of asymmetric BTAs: Asymmetric BTAs (aBTAs,
Scheme 1) were synthesised by coupling 3,5-bis-n-octylami-
nocarbonyl-benzoic acid[5a] to the appropriate chiral amine.
While (R)- and (S)-1-methylheptylamine are commercially
available, (R)- and (S)-3,7-dimethyloctylamine were synthes-
ised according to the procedure described by Koeckelberghs
et al.[13] starting from commercially available (R)- and (S)-
citronellol. Since a suitable chiral synthon is not commercial
for the b-methyl-substituted amines, (R)- and (S)-2-methyl-
octylamine were synthesised from (R)- or (S)-2-octanol
using an SN2 reaction with cyanide after tosylation of the al-
cohol group. Some racemisation occurred during the SN2 re-
action which resulted in a decrease of the enantiomeric
excess (ee) from 99% (as observed by chiral GC-FID) in
(R)- or (S)-2-octanol to 60% in (R)- or (S)-2-cyano-octane
(see Figure S1 in the Supporting Information). Since the re-
duction of 2-cyano-octane does not alter the ee, both (R)-2-
methyloctylamine and (S)-2-methyloctylamine were isolated
with ee values of 60%.
9
10
11
3239
3240
[a] All IR spectra were measured at room temperature. [b] IR vibrations
of a different crystal structure.
aBTA-S-1Me is given in Figure 2A. Interestingly, in some
BTAs, a different IR spectrum was measured after standing,
which is indicative for a different crystal packing at room
All aBTAs were obtained in high purity, as evidenced by
MALDI-TOF-MS, elemental analysis and NMR. Since the
optical purity of the amines employed was high, we can
assume that the ee of all chiral aBTAs is ꢂ 98.5%, except
for aBTA-R/S-2Me showing ee values of 60%.
IR spectroscopy of BTAs in the solid state: IR spectroscopy
is a sensitive tool to study the presence of intermolecular
hydrogen bonding in BTAs in the solid state. Vibrations for
the N H stretch at ꢀ3240 cmꢁ1, the C=O stretch at
ꢁ
ꢀ1640 cmꢁ1 and the amide II at ꢀ1560 cmꢁ1 have typically
been attributed to the presence of threefold, a-helical-type
intermolecular hydrogen bonding between neighbouring
molecules.[7a,2a,g] We can now confirm, by measuring the IR
spectrum of sBTA-methoxyethyl, which has a known crystal
structure, that indeed these values are representative for
well-defined intermolecular hydrogen bonds between neigh-
bouring molecules within the same column (Table 1, entry 1;
Figure S2A in the Supporting Information). In contrast,
sBTA-CH3 shows a completely deviating IR spectrum: two
Figure 2. A) IR spectrum of aBTA-S-1Me. B) Optical texture of aBTA-
R-1Me at 2178C (crossed polarizers) after slow cooling from the isotropic
state.
ꢁ
sharp N H stretching vibrations are observed at 3333 and
3259 cmꢁ1, whereas the amide II band is found at the low
value of 1539 cmꢁ1 (Table 1, entry 2; Figure S2B in the Sup-
porting Information). Indeed, in the crystal structure of
sBTA-CH3 no C3 symmetry is present, but in contrast lateral
hydrogen bonds are formed between the amides of mole-
cules of different stacks.
temperature (Figure S3 in the Supporting Information). For
ꢁ
example, the IR spectrum of sBTA-C8 can show an N H
stretch at the higher wavenumber of 3300 cmꢁ1 and an ami-
de II band at 1531 cmꢁ1 (Table 1, entry 4). One can trans-
form the latter crystal structure into the former by heating
up the BTA to the isotropic melt and subsequently cooling
it to room temperature. This effect was observed for sBTA-
C8, aBTA-R-3Me and aBTA-S-3Me, but not for the other
aBTAs.
All other aBTAs and sBTAs show IR vibrations at similar
ꢁ
positions, although the N H stretch vibration for sBTA-S-
3Me is at the slightly lower value of 3223 cmꢁ1 (Table 1, en-
tries 3 and 5–11). As a typical example, the IR spectrum of
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A. R. A. Palmans, E. W. Meijer et al.
Taking the IR results of sBTA-CH3 into account, the devi-
ating IR spectrum observed for sBTA-C8, for example, must
be related to the loss of the characteristic threefold intermo-
lecular hydrogen-bonding motif in the solid state. Prelimina-
ry variable-temperature IR measurements show that for
sBTA-C8, for example, the C3-symmetrical packing is not
thermodynamically stable (Figure S4 in the Supporting In-
formation). Although in the liquid-crystalline state C3-sym-
metrical packing is dominant, upon cooling and standing for
several days a rearrangement takes place. Presumably this is
related to optimising space filling in the solid state.
sBTA-S-3Me (K 120 M 235 I) are very similar to those pre-
viously reported.[7a]
Comparing the values of the transition temperatures Tm
and Tcl of aBTAs shows an increase in the Colho!I transi-
tion (Tcl) when the chiral methyl group is closer to the
amide group. Furthermore, Tcl is slightly lower in the asym-
metrically substituted BTAs, as evidenced by comparing
aBTA-R-3Me (Tcl =2168C) with sBTA-R-3Me (Tcl =2338C).
The temperature range in which aBTA-3Me displays liquid
crystallinity is much larger (over 300 K) than that of its sym-
metrical analogue (110 K). Cooling to ꢁ808C did not show
crystallisation for the asymmetric BTAs in DSC conditions,
but it is still possible that there is very slow crystallisation.
To date, BTAs have been widely studied by X-ray diffrac-
tion (XRD),[3a,b,5b] but, to the best of our knowledge,
nobody has performed XRD experiments on aligned sam-
ples of BTAs in the liquid-crystalline state. XRD patterns of
such aligned samples may confirm that the helical structure
present in crystalline N,N’,N’’-tris(2-methoxyethyl)benzene-
1,3,5-tricarboxamide is retained in the liquid-crystalline
state of analogous compounds. To confirm that the meso-
phase observed in all BTAs is indeed Colho, XRD measure-
ments were performed on (aligned) samples of selected
BTAs. The results are summarised in Table 3.
Characterisation of the mesophase of the BTAs: With the
help of POM and DSC, the thermal behaviour of the aBTAs
was investigated. Under crossed polarisers, all asymmetric
BTAs show birefringence at room temperature until the
clearing temperature is reached. Slow cooling induces the
growth of a pseudo-focal conic texture with large homeo-
tropic areas (see Figure 2B) which is typical for a columnar
hexagonal mesophase (Colho).
The melting temperatures (Tm) and clearing temperatures
(Tcl) were determined by using DSC with heating rates of
10 Kminꢁ1. All transition temperatures (in 8C) and corre-
sponding enthalpies (in kJmolꢁ1) are collected in Table 2
and were derived from the second heating run. Although
the thermal data for sBTA-C8 (K 102 LC 204 I)[3a] and
sBTA-S-3Me (K 119 Col 236 I)[7a] have been published
before, we decided to remeasure them to have data avail-
able that are obtained under identical conditions.
Table 3. Diffraction spacings in Š for BTAs.
hkl
aBTA-
1Me[a,b]
aBTA-
2Me[a,c]
aBTA-
3Me[a,c]
sBTA-
sBTA-
C8
[c]
3Me[d,e]
1 0 0
1 1 0
15.8
9.1
16.0
9.3
16.3
9.5
17.2
9.9
16.0
9.1
2 0 0
8.0
8.1
8.2
8.6
8.1
halo
interdisc
multiple
3.4
4.9
3.5
4.9
3.5
5.0
3.5
4.8
3.5
Table 2. Transition temperatures [8C] and corresponding enthalpies
[kJmolꢁ1] of sBTAs and aBTAs obtained by DSC measurements.[a]
intercolumn 18.2
18.5
18.9
19.9
18.5
Compound
K
T (DH)
Colho
T (DH)
[a] The R enantiomer was used. [b] Measurement at 1808C. [c] Measure-
ment at 1598C. [d] Measurement at 1408C. [e] Data from reference [15].
*
*
*
–
–
–
–
–
–
*
*
*
*
*
*
*
*
*
sBTA-C8
19 (17)
120 (13)
120 (9)
–
–
–
–
–
–
198 (8)
sBTA-S-3Me
sBTA-R-3Me
aBTA-R-1Me
aBTA-S-1Me
aBTA-R-2Me
aBTA-S-2Me
aBTA-R-3Me
aBTA-S-3Me
235 (18)
233 (13)
253 (24)
255 (27)
229 (15)
226 (18)
216 (12)
211 (13)
The diffraction pattern of a shear-aligned sample of
sBTA-C8 at 1598C is given in Figure 3. Two features in the
pattern allow the unambiguous assignment of a Colho phase.
First, a set of three equatorial reflections in the small-angle
pffiffi
region with spacings in the reciprocal ratio 1: 3:2 is consis-
tent with a hexagonal packing in the plane perpendicular to
the shear direction. Second, a sharp arc is centred on the
meridian and corresponds to 3.5 Š, which is the typical
stacking distance in ordered columnar mesophases. Surpris-
ingly, the diffuse halo that results from the aliphatic tails is
not isotropic in this case. The azimuthal profile shows four
distinct maxima that are about 458 off the meridian (Fig-
ure 3A). We propose two non-excluding hypotheses to ex-
plain this four split pattern (Figure 3B). First, the split can
arise from a preferred conformation of the aliphatic tails
tilted about 458 with respect to the column axis. This would
improve the packing due to the low number of aliphatic
tails to fill large spaces between the columns. Second, there
is a periodicity of 6.9 Š along the column axis, correspond-
ing to the qz component of the scattering vector of these
*
[a] all DSC data are derived from the second heating run; : phase ob-
served; –: phase not observed; K=crystalline phase; Colho =hexagonally
ordered columnar phase; I=isotropic phase.
The melting temperature found for sBTA-C8 in this study
(K 19 M 198 I) is lower than that reported by Matsunaga
et al. This can be explained by the fact that we determined
the transition temperatures from the second heating run,
whereas Matsunaga et al. derived their data from the first
heating run.[3a] In fact, in the first heating, we also observe a
broad melting peak at 1198C. Presumably, these differences
in melting temperatures are related to the different types of
packing in the crystalline state (see discussion on the IR
spectra above). In contrast, the transition temperatures for
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Asymmetrically Substituted Benzene-1,3,5-tricarboxamides
FULL PAPER
rather similar. Only sBTA-R-3Me shows a slightly larger in-
tercolumnar spacing (19.9 Š), which can be rationalised by
the three branched end groups at the aliphatic side chains.
Characterisation of aBTAs in solution with CD spectrosco-
py: To further characterise the stacking properties of the
asymmetrically substituted BTAs, their self-assembly was in-
vestigated in dilute alkane solutions. In all cases, mirror-
image CD spectra were obtained for enantiomer pairs (Fig-
ure S5 in the Supporting Information). Figure 4A shows the
CD spectra of the aBTAs with the R configuration in meth-
ylcylcohexane (MCH) at a concentration of 30 mm; the cor-
responding molar ellipticities at l=223 nm are summarised
in Table 4.
Figure 3. A) Diffraction pattern observed for aligned sBTA-C8 measured
at 1598C. B) Model showing the proposed structure of a stack based on
references [6a,b] and the characteristics of the structure, which can pro-
duce the splitting in the halo in the diffraction pattern.
maxima. This periodicity might be due to the helical struc-
ture of the stack and means that after two monomers
(3.5 Š) we return to an equivalent position. Taking into ac-
count the C3 symmetry of the molecules, there is a 608 turn
between consecutive discs. This turn is the same as that de-
scribed in the crystalline analogues[6] and allows for the
threefold intermolecular hydrogen bonding, which gives rise
to the threefold a helix. These two hypotheses are, however,
not mutually exclusive, and it can be verified that the out-
of-plane rotation of the amide groups to construct the inter-
molecular hydrogen bonds leads to a necessary tilt of about
458 of the alkyl tails with respect to the aromatic ring (Figur-
e 3B).[6b] We thus think that the split in the halo due to the
aliphatic tails proves that the helical structure in the liquid-
crystalline phase is indeed the same as in the crystalline
solids.
*
Figure 4. A) CD spectra of aBTA-R-1Me ( ), aBTA-R-2Me (c) and
*
aBTA-R-3Me ( ) at a concentration of 30 mm in MCH at 208C. B) CD
spectra of aBTA-S-2Me (c) at a concentration of 30 mm and aBTA-S-
2MeBu ( ) at a concentration of 140 mm in MCH at 208C.
*
The positive Cotton effects observed for the a- and g-
methyl-substituted aBTAs and the negative Cotton effect of
the b-methyl-substituted aBTA indicate the presence of the
odd–even effect. Whereas the shape and strength of the
Cotton effect of aBTA-R-1Me (De=41 Lmolꢁ1 cmꢁ1) and
aBTA-R-3Me (De=39 Lmolꢁ1 cmꢁ1) are almost identical,
the shape of the Cotton effect of aBTA-R-2Me differs. The
Unfortunately we could not achieve appropriate align-
ment of samples for the aBTAs. The powder patterns at
high temperatures are, however, analogous to that of sBTA-
C8, which confirms a Colho phase for all aBTAs.[14] The inter-
columnar distances found in the aBTAs and sBTAs are
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A. R. A. Palmans, E. W. Meijer et al.
Table 4. Molar ellipticities (De) of aBTAs at l=223 nm in MCH at 208C
and he values determined from CD cooling curves and from van ꢂt Hoff
plots.
Compound
De
[Lmolꢁ1 cmꢁ1
Te[a]
[K]
he (S.D.)[a]
[kJmolꢁ1
he (R2)[b]
[kJmolꢁ1
]
]
G
]
U
aBTA-R-1Me
aBTA-S-2Me
aBTA-R-3Me
aBTA-S-2MeBu
sBTA-R-3Me[d]
41
39
39
9
43
0
339.7 ꢁ59.7 (ꢃ0.8) ꢁ69.4 (0.99)
336.2 ꢁ55.6 (ꢃ0.7) ꢁ69.8 (0.99)
333.9 ꢁ59.8 (ꢃ0.6) ꢁ68.6 (0.99)
n.d.[c] n.d.[c]
345.9 ꢁ60.9
350.0 ꢁ69.6
n.d.[c]
ꢁ66.0
ꢁ75.0
[e]
sBTA-C8
[a] Derived from the CD cooling curves, c=20 mm in MCH, S.D.=stan-
dard deviation. [b] Derived from the van ꢂt Hoff plot. [c] n.d. =not deter-
mined. [d] Data from reference [7b], c=21 mm in heptane. [e] Data from
reference [7b], c=22 mm in heptane, data derived from UV measure-
ments.
molar ellipticity at 223 nm (De=ꢁ39 Lmolꢁ1 cmꢁ1), on the
other hand, is similar in magnitude despite its lower enantio-
meric excess (ee) value of 60%. Remarkably, the values for
De of the aBTAs comprising only one chiral centre are close
to the value of 43 Lmolꢁ1 cmꢁ1 previously found for sBTA-
R-3Me (Table 4), which has three chiral centra.[7b]
To rule out the possibility that the lower ee value is re-
sponsible for the different shape of the CD effect in the b-
methyl-substituted aBTA, we prepared aBTA-S-2MeBu
(Scheme 1) from (S)-2-methylbutylamine (ee>99%). The
shape of the CD spectra of both b-methyl-substituted
aBTAs is similar (Figure 4B). However, the molar ellipticity
of aBTA-S-2MeBu (De=9 Lmolꢁ1 cmꢁ1 at 223 nm) is about
four times smaller than that of aBTA-S-2Me (De=
39 Lmolꢁ1 cmꢁ1 at 223 nm). This large difference can be at-
tributed to two different effects. First, there is low asymme-
try around the chiral centre of aBTA-S-2MeBu and second,
its chiral side chain is much shorter than the achiral side
chains, resulting in a highly asymmetric system. The latter
may result in poorer aggregation.
~
&
*
Figure 5. A) CD spectra of aBTA-R-1Me at 19 ( ), 30 ( ), 44 ( ) and
!
49m ( ) at 208C. B) Results of the temperature-dependent CD measure-
ments of aBTA-R-1Me at 19 ( ), 30 ( ), 44 ( ) and 49m ( ) in MCH
monitored at l=223 nm.
~
!
&
*
at around room temperature. Clearly, Te increases with in-
creasing concentration, indicative for the earlier (when cool-
ing down from 908C) formation of aggregates.
Stability of BTA stacks in MCH solution: The influence of
the position of the methyl group on the stability of the
aBTA aggregates in solution was investigated with tempera-
ture-dependent CD measurements at different concentra-
tions in MCH. The temperature was decreased from 90 to
208C at l=223 nm because this is the maximum of the
Cotton effect for aBTA-R-1Me and aBTA-R-3Me. The re-
sults are summarised in Figure 5; additional curves are given
in Figure S5 in the Supporting Information.
As expected, the intensity of the CD effect decreases with
decreasing concentration (Figure 5A).[7b] A typical tempera-
ture-dependent CD measurement at different concentra-
tions is shown in Figure 5B. The curves in Figure 5B reveal
two regimes; a nucleation regime, in which all molecules are
molecularly dissolved (indicated by the absence of a CD
effect) and an elongation regime in which the aggregate rap-
idly grows. Upon cooling, at a certain (concentration-depen-
dent) temperature, the elongation temperature Te, a large
enough nucleus is formed to allow the formation of an ag-
gregate. The increase in the degree of aggregation levels off
Quantitative data on the self-assembly process can be de-
rived from the CD cooling curves by fitting the data to a re-
cently developed nucleation-growth model by van der
Schoot,[16] which is a modified version of a model originally
developed by Oosawa and Kasai.[17] We recently successfully
used this model to describe the aggregation behavior of
sBTA-R-3Me and sBTA-C8.[7b] Fitting the cooling curves to
the model affords Te (the elongation temperature) and he
(the enthalpy release upon elongation). Moreover, a dimen-
sionless equilibrium constant Ka can be derived that reflects
the degree of cooperativity in the aggregation process. The
results of Te and he as a function of the concentration are
given in Figure 6 and the data for a 20 mm solution are
shown in Table 4. All relevant thermodynamic data are col-
lected in Table S5 in the Supporting Information.
Figure 6 and Table 4 show that aBTA-R-1Me has a slight-
ly higher Te than aBTA-S-2Me, which in turn has slightly
higher Te than aBTA-R-3Me, indicating that shifting the
methyl moiety closer to the core gives a more stable aggre-
2076
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Chem. Eur. J. 2009, 15, 2071 – 2080

Asymmetrically Substituted Benzene-1,3,5-tricarboxamides
FULL PAPER
cules, as inferred from IR measurements in the solid state.
In some cases, packing effects in the crystalline state result
in a rearrangement of the hydrogen bonds, causing the loss
of the characteristic threefold hydrogen-bonding motif.
However, in the liquid-crystalline state, a-helical-type inter-
molecular hydrogen bonding is dominant. X-ray diffraction
measurements confirm that all derivatives are in a Colho
phase above Tm and that helical columnar order is preserved
in the liquid-crystalline state. Moving the methyl group
closer to the amide moiety, results in a stabilisation of the
mesophase, as seen in the increase in Tcl from 216 to 2538C
and a concomitant increase in the transition enthalpies DH.
Although there are small differences in the length of the
chiral side chains, the observed differences in the Tcl are
larger than expected based on the number of carbon atoms
in the chiral side chain.
In dilute alkane solutions, the molar ellipticity (De) of all
aBTAs is around ꢃ40 Lmolꢁ1 cmꢁ1, which suggests that the
degree to which the chirality of the side chain is transferred
to the helical aggregate is independent of the position of the
methyl group. This in contrast to induction of chirality in
chiral polythiophenes and polyisocyanides; in these systems
the Cotton effect decreases rapidly when the chiral substitu-
ent is placed further from the chromophore.[10a,11a,12] The sta-
bility of the aggregation process is affected by the position
of the methyl group: Te increases from 60.98C for the g-
methyl aBTA to 66.78C for the a-methyl aBTA. Unexpect-
edly, the position of the methyl group at an odd or an even
position has a clear influence on the shape of the CD effect:
in aBTA-S-2Me the CD spectrum shows a lmax at 216 nm
and a shoulder at 240 nm. As is clear from Figure 7, the spa-
tial position of the methyl at an odd or even position is dif-
ferent with respect to its vicinity to the C=O group. This
may inflict small changes in packing and hydrogen-bond
lengths, which affect the shape of the CD spectra.
Figure 6. A) he as a function of concentration and B) Te as a function of
concentration, the standard deviations given for he result from the fit of
the van der Schoot model. No standard deviations are displayed for the
*
*
:
Te because they are too small (typically ꢃ0.05 K). : aBTA-R-1Me,
~
aBTA-R-3Me and : aBTA-S-2Me.
gate. The he values derived from the CD melting curves are
between ꢁ55 and ꢁ59 kJmolꢁ1 and are concentration inde-
pendent (Figure 6A). Interestingly, aBTA-S-2Me shows a
slightly lower enthalpy release (he =ꢁ55.6 kJmolꢁ1) than the
other aBTAs, which may be related to its lower ee value. All
Ka values are very small (=10ꢁ5/10ꢁ6), indicating a highly co-
operative system.
Conclusion
Asymmetrically substituted, chiral benzene-1,3,5-tricarboxa-
mides are readily synthesised by coupling chiral amines to
3,5-bis-n-octylaminocarbonylbenzoic acid. In these aBTAs,
the chiral methyl group varies in configuration (R or S) and
position (a, b or g) with respect to the amide group. IR
spectroscopy revealed that in the solid state the aBTAs
form columnar structures through threefold, a-helical-type
intermolecular hydrogen bonding. All aBTAs are liquid
crystalline at room temperature and with X-ray diffraction
studies we could determine that the mesophase is Colho in
all cases. Shifting the chiral methyl group in the aliphatic
side chain closer to the amide bond stabilises the columnar
structure as evidenced by an increase in the clearing temper-
ature and enthalpy. In dilute solution, cooperative growth
characterises the formation of aBTA aggregates, and
moving the methyl group closer to the benzene core results
in a more stable aggregate. A clear odd–even effect is pres-
ent for aBTAs in dilute alkane solutions, and the degree to
Fitting the natural logarithm of the (dimensionless)
Cotton effect versus the reciprocal Te allows for the con-
struction of a modified van ꢂt Hoff plot (Figure S6 in the
Supporting Information), which provides a second method
to determine the he value.[7b] The data are summarised in
Table 4. The enthalpies obtained (ꢀꢁ69 kJmolꢁ1) are simi-
lar for all aBTAs and in between those previously reported
for
sBTA-R-3Me
(ꢁ66 kJmolꢁ1)
and
sBTA-C8
(ꢁ75 kJmolꢁ1).
Discussion
aBTAs show the presence of threefold, a-helical-type inter-
molecular hydrogen bonding between neighbouring mole-
Chem. Eur. J. 2009, 15, 2071 – 2080
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2077

A. R. A. Palmans, E. W. Meijer et al.
(ꢁ)-3,7-dimethyloctylamine, (R)-(+)-3,7-dimethyloctylamine and (S)-
(ꢁ)-2-methylbutylamine[20] were synthesised following the procedures de-
[2a]
scribed by Koeckelberghs et al.[13] Reference compounds sBTA-CH3
and sBTA-methoxyethyl[6a] were prepared as described previously and re-
cystallised from water and methanol, respectively. All solvents were ob-
tained from Biosolve, except for DMSO (Acros) and spectrophotometric
grade methylcylcohexane (Aldrich). All other chemicals were obtained
from either Acros or Aldrich. Dry THF was tapped off a distillation
setup which contained molecular sieves, CHCl3 was dried over molsieves
and triethylamine was stored on KOH pellets. All other chemicals were
used as received.
Methods: UV/Vis and circular dichroism measurements were performed
on a Jasco J-815 spectropolarimeter where the sensitivity, time constant
and scan rate were chosen appropriately. Corresponding temperature-de-
pendent measurements were performed with a PFD-425S/15 Peltier-type
temperature controller with a temperature range of 263–383 K and ad-
justable temperature slope, in all cases a temperature slope of 1 Kminꢁ1
was used. In all other measurements the temperature was set at 208C. In
all experiments the linear dichroism was also measured and in all cases
no linear dichroism was observed. Separate UV/Vis spectra were ob-
tained from a Perkin–Elmer UV/Vis spectrometer Lambda 40 at 208C.
Cells with an optical path length of 1 cm were employed and spectroscop-
ic grade solvents were employed. Solutions were prepared by weighing in
the necessary amount of compound for a given concentration, whereafter
this amount was transferred to a volumetric flask (flasks of 10, 25 and
3
50 mL were employed). Then the flask was filled for = with the spectro-
4
scopic grade solvent and put in an oscillation bath at 408C for 45 min,
whereafter the flask was allowed to cool down and filled up to its menis-
cus. The anisotropy value g was calculated from De and e: g=De/e and
De=CD effect/(32980·c·l) in which c is the concentration in mol/L and l
is the optical path length in cm. Optical rotations were recorded at room
temperature on a Jasco DIP-370 polarimeter at a wavelength of 589 nm
(NaD-line). 1H and 13C NMR spectroscopy measurements were conduct-
ed on a Varian Mercury 200 MHz and/or a Varian Gemini 400 MHz.
Proton chemical shifts are reported in ppm downfield from tetramethylsi-
lane (TMS). Carbon chemical shifts are reported using the resonance of
CDCl3 as internal standard. Maldi-TOF-MS were acquired using a Per-
serptive Biosystem Voyager-DE PRO spectrometer. In all cases, a-cyano-
4-hydroxycinnamic acid was employed as the matrix material. Elemental
analyses were performed on a Perkin–Elmer 2400 series II CHNS/O ana-
lyser. IR spectra were recorded on a Perkin–Elmer spectrum 1 using a
universal ATR. Polarisation optical microscopy measurements were done
using a Jenaval polarisation microscope equipped with a Linkam THMS
600 heating device, with crossed polarizers. The thermal transitions were
determined with DSC using a Perkin–Elmer Pyris 1 DSC under a nitro-
gen atmosphere with heating and cooling rates of 10 Kminꢁ1. The Tg was
determined with heating and cooling rates of 40 Kminꢁ1. The XRD pat-
terns were obtained with a pinhole camera (Anton-Paar) operating with
a point-focused Ni-filtered CuKa beam. In this setup, the samples are held
in Lindemann glass capillaries (0.9 mm diameter). Aligned samples are
obtained by shearing inside the capillary at the temperature of the meso-
phase, typically at 1608C. The capillary axis is perpendicular to the X-ray
beam and the pattern is collected on a flat photographic film perpendicu-
lar to the beam. Spacings are obtained via Braggꢂs law (nxl= 2xdxsinq).
The ee values of (R)- and (S)-2-cyano-octane were determined with GC-
FID measurements using a Perkin–Elmer autosystem GC equipped with
a WCOT fused silica column of 25 m”0.25 mm with a CP Chirasel DEX
CB DF=0.12 coating. Separation of the enantiomers was performed
under isothermal conditions with an oven temperature of 808C and a
pressure of 11.6 or 12.0 psi. The ee values of commercially available (R)-
and (S)-citronellol were measured on a Shimadzu GC-17A equipped
with an FID detector and employing a Rt-bDex saTM column of Restek.
Separation of the enantiomers was achieved using isothermal conditions
with an oven temperature of 1008C. In all cases, injection and detection
temperatures were set at 2508C.
Figure 7. CPK models of aBTAs with a substituent at the 1 and 3 posi-
tions (R configuration) highlighted in yellow and at the 2 position (S con-
figuration) highlighted in orange.
which the chirality of the side chain is transferred to the hel-
ical aggregate is independent of the position of the methyl.
Unexpectedly, we found that the shape of the CD effect
differs when the methyl group is placed at an odd or an
even position. The subtleties involved in the packing of
aBTA-R/S-3Me, aBTA-R/S-2Me or aBTA-R/S-1Me are in-
triguing and currently we are performing vibrational CD
(VCD) measurements on the aBTAs in solution to gather
further information on packing effects. Moreover, we are
performing sergeants-and-soldiers[18] and majority-rules ex-
periments[19] to evaluate the impact of the position of the
methyl group on the amplification of chirality in these sys-
tems. With this systematic study on the effect of the position
of the chiral methyl goup in BTAs, we expect to increase
our understanding of the subtleties involved in the self-as-
sembly processes of seemingly simple compounds. Ultimate-
ly, our goal is to extend this understanding to achieve a
design-driven, non-covalent synthesis of complex, functional
supramolecular assemblies.
Experimental Section
Materials: (S)-Citronellol was obtained from Takasago, (98.4%ee), (R)-
citronellol was obtained from Aldrich, 99%ee, (S)-2-octanol was ob-
tained from Chiraselect (99.5%ee), (R)-2-octanol was obtained from
Janssen Chimica (99%ee), (S)-2-octylamine was obtained from ABCR
(99%ee, [a]2D3 =6.16, neat). (R)-2-octylamine was obtained from ABCR
(99%ee, [a]2D3 =ꢁ5.99, neat), (S)-2-methylbutanol was obtained from
Acros ([a]2D3 =ꢁ5.80, neat). 3,5-Bis(n-octylaminocarbonyl)benzoic acid
was synthesised according to a previously published procedure.[5a] (S)-
Synthesis of (S)-(ꢁ)-2-methyloctylamine and (R)-(+)-2-methyloctyla-
mine: A 100 mL three-necked round-bottom flask was charged with a so-
lution of (S)-(+)-2-octanol (8.70 g, 0.0668 mol) in pyridine (20 mL), while
keeping the solution at ꢁ58C in an ice/salt bath under an argon atmos-
2078
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Chem. Eur. J. 2009, 15, 2071 – 2080

Asymmetrically Substituted Benzene-1,3,5-tricarboxamides
FULL PAPER
phere. Subsequently, p-toluenesulfonyl chloride (1.1 equiv, 14.03 g,
0.0735 mol) was added to the mixture and the mixture was stirred over-
night at 48C. After completion of the reaction was comfirmed by
1H NMR spectroscopy, the excess p-toluenesulfonyl chloride was slowly
quenched in small portions with cold H2O. Subsequently, cold H2O
(100 mL) was added to the solution. This mixture was then extracted
with CHCl3 (3”100 mL), the organic layers were collected and washed
with 1m H2SO4 (3”100 mL) and 0.4m CuSO4 (3”100 mL) until no color
change was observed in the copper sulfate, then the solution was washed
once with H2O. Drying of the organic layer with MgSO4, filtration and
concentration of the filtrate gave (S)-2-p-toluenesulfonate octane as a
colorless oil (17.45 g, 92%). 1H NMR (CDCl3): d=7.79 (d, 2H; Ar-H),
7.35 (d, 2H; Ar-H), 4.63 (sextett, 1H; O-CH), 2.45 (Ar-CH3), 1.64–
0.80 ppm (m, 16H; CH2, CH3). A 250 mL three-necked round-bottom
flask was charged with a solution of (S)-2-p-toluenesulfonate octane
(14.99 g, 0.052 mol) in DMSO (70 mL) under an argon atmosphere with
a gas wash bottle filled with 1m NaOH at the end of the gasflow. The
mixture was heated to 508C. Subsequently, NaCN (1.1 equiv, 2.26 g,
0.057 mol) was added to the solution and the mixture was stirred over-
night at 508C under an argon atmosphere. After the reaction was com-
pleted, the mixture was allowed to cool to room temperature, after which
time it was transferred to a separating funnel and water (560 mL) was
added. The water layer was extracted with CH2Cl2 (3”100 mL), the or-
ganic layers were collected and washed with 1m KCl (3”100 mL). After
evaporation in vacuo the crude product was obtained as a dark-brownish
oil. Vacuum distillation afforded (R)-2-cyano-octane as a yellowish oil
(4.46 g, 62%, b.p. 568C at 0.27 mbar). 1H NMR (CDCl3): d=2.65–2.38
(m, 1H; CN-CH), 1.66–1.18 (m, 13H; CH2, CH3), 0.89 ppm (t, 3H; CH3),
trace amounts of 2-octanol; 13C NMR (CDCl3): d=123.0 (C=N), 34.0
(CH2), 31.5 (CH2), 28.7 (CH2), 26.9 (CH2), 25.4 (CH), 22.4 (CH2), 17.9
(CH3), 13.9 ppm (CH3), trace amounts of 2-octanol. A 250 mL three-
necked round-bottom flask was charged with a solution of 1m borane-
THF-complex (60 mL) in dry THF (25 mL), while keeping the solution
at 08C and under an argon atmosphere. A solution containing (R)-2-
cyano-octane (4.00 g, 0.029 mol) in dry THF (25 mL) was slowly added to
the reaction mixture through a dropping funnel. The mixture was stirred
for 30 min at 08C, after which the mixture was heated at reflux for 1 h.
Finally the mixture was stirred overnight at room temperature. After this,
the mixture was cooled to 08C, and methanol (60 mL) was added drop-
wise (CAUTION! hydrogen gas is formed). Hydrochloric acid (37% in
water, 7 mL) was added slowly; the reaction mixture was stirred for 1 h
and subsequently evaporated to dryness in vacuo. 2m NaOH (100 mL)
was added to the resulting viscous liquid and this was extracted with di-
ethyl ether (3”200 mL). The organic layers were collected and dried
with sodium sulfate, filtered and the solvent was removed in vacuo to
obtain (R)-(+)-2-methyl-octylamine as a yellowish liquid (3.68 g, 88.6%)
1H NMR (CDCl3): d=2.68–2.41 (m, 2H; NH2-CH2), 2.03 (s, 2H; NH2),
1.62–1.15 (m, 11H; CH, CH2), 0.96–0.85 ppm (m, 6H; CH3), trace
amounts of 2-octanol; [a]2D3 =4.05 (neat). (S)-(ꢁ)-2-methyloctylamine was
obtained in a similar fashion and obtained as a yellowish liquid (1.26 g,
C), 29.5 (CH2), 29.3 (CH2), 29.2 (CH2), 27.0 (CH2), 22.6 (CH2), 14.1 ppm
(CH3); IR: n˜ =3236 (NH stretch), 1640 (C=O), 1557 cmꢁ1 (amide II);
MS (Maldi-TOF): m/z: 566.30 Da [M+Na+]; elemental analysis calcd
(%) for C33H57N3O3 (543.82 gmolꢁ1) C 72.88, H 10.56, N 7.73; found: C
72.77, H 10.90, N 7.45. observed DSC transitions: Tm =19.88C, DH=
16.6 kJmolꢁ1; Tcl =198.48C, DH=8.50 kJmolꢁ1
sBTA-S-3Me: sBTA-S-3Me was obtained as
.
a
white solid (0.77 g,
63%).1H NMR (CDCl3): d=8.35 (s, 3H; Ar-H), 6.45 (t, 3H; N-H), 3.50
(m, 6H; NH-CH2), 1.67–1.10 (m, 36H; CH, CH2), 0.96 (d, 9H; CH3),
0.88 ppm (d, 18H; 2”CH3); IR: n˜ =3223 (NH stretch), 1637 (C=O),
1564 cmꢁ1 (amide II); MS (Maldi-TOF): m/z: 650.47 Da [M+Na+]; ele-
mental analysis calcd (%) for C39H69N3O6 (627.97 gmolꢁ1) C 74.59, H
11.07, N 6.69; found: C 74.01, H 10.94, N 6.63; observed DSC transitions:
Tm =119.78C, DH=13.2 kJmolꢁ1; Tcl =234.98C, DH=18.2 kJmolꢁ1
.
sBTA-R-3Me: sBTA-R-3Me was obtained as a white solid (0.39 g, 33%).
1H NMR (CDCl3): d=8.34 (s, 3H; Ar-H), 6.40 (t, 3H; N-H), 3.49 (m,
6H; NH-CH2), 1.69–1.14 (m, 36H; CH, CH2), 0.95 (d, 9H; CH3),
0.87 ppm (d, 18H; 2”CH3). IR: n˜ =3222 (NH stretch), 1637 (C=O),
1566 cmꢁ1 (amide II); MS (Maldi-TOF): m/z: 650.48 Da [M+Na+]; ele-
mental analysis calcd (%) for C39H69N3O6 (627.97 gmolꢁ1): C 74.59, H
11.07, N 6.69; found: C 74.31, H 10.96, N 6.56; observed DSC transitions:
Tm =120.08C, DH=9.3 kJmolꢁ1; Tcl =232.98C, DH=12.9 kJmolꢁ1
.
General procedure for the synthesis of aBTAs: A 100 mL three-necked
round-bottom flask was charged with a solution of 3,5-bis(n-octylamino-
carbonyl)benzoic acid (0.220 g, 0.509 mmol), DMAP (1.7 equiv, 0.106 g)
and the appropriated amine (1.7 equiv, 0.865 mmol)[21] in dry CHCl3
(30 mL) under an argon atmosphere; the solution was cooled in an ice/
salt bath. A solution containing 1-(3-dimethylpropyl)-3-ethylcarbodiimide
hydrochloride (EDC; 1.7 equiv, 0.162 g, 0.865 mmol) in dry CHCl3
(10 mL) was quickly added to the reaction mixture. The solution was
stirred for 4 d under an argon atmosphere. The mixture was then trans-
ferred to a separating funnel and CHCl3 (50 mL) was added and subse-
quently washed with 1m HCl (50 mL), 10% aqueous NaHCO3 (50 mL)
and brine (50 mL). The solvent was removed in vacuo before the crude
product was purified by means of column chromatography. Column chro-
matography was performed by using silica gel (9 g) in a column with a di-
ameter of 1.5 cm; the silica was equilibrated in CHCl3. Because of the
relatively poor solubility of the crude product in chloroform, the crude
product was dissolved in a large volume of chloroform, silica gel was
added (around 1 g), the mixture was stirred for 15 min and was evaporat-
ed to dryness in vacuo. This impregnated silica was then poured on top
of the column. The eluent was then applied (chloroform/ethyl acetate 8:2
v/v) and the product fractions were collected (monitored by TLC) and
the solvent was removed in vacuo to obtain a white solid.
aBTA-S-3Me: aBTA-S-3Me was obtained as
a sticky white solid
(0.1634 g, 56%). 1H NMR (CDCl3): d=8.34 (s, 3H; Ar-H), 6.41 (t, 3H;
N-H), 3.50 (m, 6H; NH-CH2), 1.72–1.13 (m, 36H; CH, CH2), 0.96
ꢁ0.85 ppm (m, 15H; CH3); IR: n˜ =3240 (NH stretch), 1639 (C=O),
1563 cmꢁ1 (amide II); MS (Maldi-TOF): m/z: 594.50 [M+Na+]; observed
DSC transitions: Tcl =211.28C, DH=12.8 kJmolꢁ1
.
1
80.0%). H NMR (CDCl3): d=2.71–2.41 (m, 2H; NH2-CH2), 1.86 (s, 2H;
NH2), 1.62–1.17 (m, 11H; CH, CH2), 1.00–0.86 ppm (m, 6H; CH3), trace
aBTA-R-3Me: aBTA-R-3Me was obtained as
a sticky white solid
amounts of 2-octanol; [a]2D3 =ꢁ4.10 (neat).
1
(0.0904 g, 68.7%). H NMR (CDCl3): d=8.33 (s, 3H; Ar-H), 6.55 (t, 3H;
N-H), 3.45 (m, 6H; NH-CH2), 1.73–1.14 (m, 31H; CH, CH2), 0.94–
0.83 ppm (m, 15H; CH3); IR: n˜ = 3239 (NH stretch), 1636 (C=O),
1558 cmꢁ1 (amide II); MS (Maldi-TOF): m/z: 594.36 [M+Na+]; observed
General procedure for the synthesis of sBTAs: A 100 mL three-necked
round-bottom flask was charged with a solution of the appropriated
amine (62.2 mmol), triethylamine (1 equiv, 0.67 g, 66.2 mmol) in dry
CHCl3 (35 mL, stabilised with amylene) under inert atmosphere. A solu-
tion containing 1,3,5-benzenetricarboxylic acid chloride (0.3 equiv, 0.5 g,
18.8 mmol) in dry CHCl3 (15 mL, stabilised with amylene) was slowly
added dropwise to this solution. The solution was stirred overnight under
inert atmosphere. The reaction mixture was then transferred to a separat-
ing funnel and washed with 1m HCl (40 mL, check for acidity, pH<1).
The organic layer was collected and the solvent was removed in vacuo.
The obtained crude product was then purified by recrystallisation from
ethanol to obtain a white powder.
DSC transitions: Tcl =215.98C, DH=11.8 kJmolꢁ1
aBTA-R-2Me: aBTA-R-2Me was obtained as
.
a
sticky white solid
(0.1363 g, 48%). 1H NMR (CDCl3): d=8.38 (s, 3H; Ar-H), 6.43 (t, 3H;
N-H), 3.55–3.27 (m, 6H; NH-CH2), 1.73–1.16 (m, 31H; CH, CH2), 1.02–
0.84 ppm (m, 15H; CH3); IR: n˜ =3240 (NH stretch), 1638 (C=O),
1556 cmꢁ1 (amide II); MS (Maldi-TOF): m/z: 558.36 Da [M+H+]; ob-
served DSC transitions: Tcl =229.28C, DH=14.9 kJmolꢁ1
aBTA-S-2Me: aBTA-S-2Me was obtained as
.
a
sticky white solid
(0.1326 g, 47%). 1H NMR (CDCl3): d=8.34 (s, 3H; Ar-H), 6.48 (t, 3H;
N-H), 3.50–3.27 (m, 6H; NH-CH2), 1.75–1.14 (m, 35H; CH, CH2), 1.00–
0.84 ppm (m, 12H; CH3); IR: n˜ =3240 (NH stretch), 1637 (C=O),
1557 cmꢁ1 (amide II); MS (Maldi-TOF): m/z: 580.34 Da [M+Na+]; ob-
sBTA-C8: sBTA-C8 was obtained as a white solid (3.5 g, 54.9%).1H NMR
(CDCl3): d=8.34 (s, 3H; Ar-H), 6.56 (t, 3H; N-H), 3.47 (q, 6H; NH-
CH2), 1.68–1.28 (m, 36H; CH2), 0.91 ppm (t, 9H; CH3); 13C NMR
(CDCl3): d=166.3 (C=O), 135.3 (Ar-C-C=O), 127.8 (Ar-C), 31.8 (NH-
served DSC transitions: Tcl =226.08C, DH=18.4 kJmolꢁ1
.
Chem. Eur. J. 2009, 15, 2071 – 2080
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2079

A. R. A. Palmans, E. W. Meijer et al.
aBTA-R-1Me: aBTA-R-1Me was obtained as
a
sticky white solid
[4] a) M. Blomenhofer, S. Ganzleben, D. Hanft, H.-W. Schmidt, M.
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2394–2404.
(0.1761 g, 46%). 1H NMR (CDCl3): d=8.25 (s, 3H; Ar-H), 6.80 (t, 2H;
N-H), 6.47 (d, 1H; N-H), 4.16 (sextett, 1H; NH-CH), 3.45 (q, 4H; NH-
CH2), 1.68–1.17 (m, 36H; CH2), 0.88 ppm (t, 9H; CH3); IR: n˜ =3234
(NH stretch), 1634 (C=O), 1556 cmꢁ1 (amide II); MS (Maldi-TOF): m/z:
566.33 Da [M+Na+]; elemental analysis calcd (%) for C33H57N3O3
(543.82 gmolꢁ1): C 72.88, H 10.56, N 7.73; found: C 72.75, H 10.45, N
7.74; observed DSC transitions: Tcl =252.98C, DH=24.1 kJmolꢁ1
aBTA-S-1Me: aBTA-S-1Me was obtained as sticky white solid
.
a
(0.1828 g, 48%). 1H NMR (CDCl3): d=8.25 (s, 3H; Ar-H), 6.77 (t, 2H;
N-H), 6.47 (d, 1H; N-H), 4.16 (sextett, 1H; NH-CH), 3.45 (q, 4H; NH-
CH2), 1.66–1.16 (m, 36H; CH2), 0.90 ppm (t, 9H; CH3); IR: n˜ =3235
(NH stretch), 1635 (C=O), 1556 cmꢁ1 (amide II); MS (Maldi-TOF): m/z:
566.38 Da [M+Na+]; elemental analysis calcd (%) for C33H57N3O3
(543.82 gmolꢁ1): C 72.88, H 10.56, N 7.73; found: C 72.43, H 10.43, N
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7.73; observed DSC transitions: Tcl =255.08C, DH=26.5 kJmolꢁ1
.
[8] The solubility of N,N’,N’’-tris((S)-1-methylheptyl)benzene-1,3,5-tri-
carboxamide and N,N’,N’’-tris((R)-1-methylheptyl)benzene-1,3,5-tri-
carboxamide was below 10ꢁ6 m in MCH.
aBTA-S-2MeBu: aBTA-S-2MeBu was obtained as a sticky white solid
(0.070 g, 60%). H NMR (CDCl3): d=8.30 (s, 3H; Ar-H), 6.41 (t, 3H; N-
1
H), 3.44–3.22 (m, 6H; NH-CH2), 1.60–1.15 (m, 27H; CH, CH2), 0.94–
0.77 ppm (m, 12H; CH3). IR: n˜ =3239 (NH stretch), 1639 (C=O),
1558 cmꢁ1 (amide II); MS (Maldi-TOF): m/z: 524.47 Da [M+Na+]; ob-
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17; b) G. W. Gray, D. G. McDonnel, Mol. Cryst. Liq. Cryst. 1977, 34,
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served DSC transitions: Tcl =222.68C,[22] DH=2.2 kJmolꢁ1
.
Acknowledgements
The authors would like to thank Dr. J. A. J. M. Vekemans for stimulating
discussions, Martijn Gillissen, Fokko Haveman and Dirk Balkenende for
their help with the synthesis and the NRSC-C and NWO for financial
support. R.M.-R. acknowledges support from an EU Marie Curie Intra-
European Fellowship (Project MEIF-CT-2006-042044) within the EC
Sixth Framework Program. We gratefully thank Dr. J. Barberµ for pro-
viding us access to the powder X-ray diffraction equipment at the Uni-
versity of Zaragoza (ES) and Philips Research in Eindhoven (NL) for al-
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were observed in the second and consecutive runs.
Received: October 23, 2008
Published online: January 13, 2009
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