Synthesis and NMR Spectroscopic Study of the Self-Aggregation of 2-Substituted Benzene-1,3,5-tricarboxamides

Article abstract of DOI:10.1002/ejoc.201500506

The self-assembly of N,N′,N′-trialkylbenzene-1,3,5-tricarboxamides (BTAs) 1 or of "crowded" BTAs 11 and 12 lead to supramolecular columnar-stacked structures with attractive material properties. The introduction of three alkoxy groups is reported to reinf

Full text of DOI:10.1002/ejoc.201500506

FULL PAPER
DOI: 10.1002/ejoc.201500506
Synthesis and NMR Spectroscopic Study of the Self-Aggregation of
2-Substituted Benzene-1,3,5-tricarboxamides
Christian Invernizzi,[a] Claudio Dalvit,[b] Helen Stoeckli-Evans,[c] and Reinhard Neier*[a]
Keywords: Supramolecular chemistry / Self-assembly / Hydrogen bonds / Pi interactions / Liquid crystals
The self-assembly of N,NЈ,NЈЈ-trialkylbenzene-1,3,5-tricarb-
oxamides (BTAs) 1 or of “crowded” BTAs 11 and 12 lead to
supramolecular columnar-stacked structures with attractive
material properties. The introduction of three alkoxy groups
is reported to reinforce the self-assembly process. The influ-
ence of a single substituent introduced onto the aromatic
core of BTA significantly affects the self-assembly process.
The aggregation process of 2-substituted BTAs in the bulk
and in solution, as studied by DSC, POM, X-ray diffraction
and 1H NMR experiments, is impaired by hydrogen-bond-
accepting substituents but strengthened by non-hydrogen-
bond-accepting substituents.
of our studies was a simple design exploring linear dimers
with minimal disturbance of the benzenetricarboxamide ba-
sic structure. The physical properties of interest in such
mesomorphic materials, such as 1D charge transport,
strongly depend on the molecular alignment in the liquid
crystalline phases.[10] Enhanced control over self-organiza-
tion of discotic compounds is expected by covalently link-
ing two discotic units through a rigid linker.[9b,11] This ap-
proach aims to create an interface between materials by
using nano-sized structures and microtechnology. Predic-
ting reliably the efficiency of the self-assembly process and
as a consequence the material properties is still the biggest
challenge.
Introduction
Understanding the processes that create order from sim-
ple building blocks is the key to deepening our insight into
the life and material sciences.[1] Data identifying and quan-
tifying interactions in solution and correlating them with
material properties help to overcome the gap between mod-
els based on the interplay between individual molecules and
material properties. The relatively small number of widely
known interactions responsible for self-assembly are com-
bined with a wealth of empirical data. “Our ability to pre-
dict the structural features and the functional outcome of
the assembled materials is still limited and most of the
learning is done in retrospect”.[2] N,NЈ,NЈЈ-Trialkylbenzene-
The first synthesis of BTAs was achieved by Curtius in
1915.[12] In their pioneering work published in 1988, Mat-
sunaga et al. reported the first controlled fabrication of co-
lumnar liquid crystals based on BTA as a fundamental unit
(Figure 1, a).[3] The discovery of the liquid crystalline be-
haviour of 1 stimulated intense studies of BTA derivatives.
Detailed studies by Meijer and co-workers elucidated the
cooperative nature of the supramolecular assembly.[13] The
nucleation constant Kn and the elongation constant Ke of
the cooperative aggregation process of the N,NЈ,NЈЈ-trioct-
ylbenzene-1,3,5-tricarboxamide derivative were determined
by these authors.[13b] An impressive number of modifica-
tions of BTAs have been reported, varying the lateral
chains, introducing stereogenic centres into the chains,[14]
changing the polarity[6] and adding gallic acid elements to
impose additional π stacking.[15] Nuckolls and co-workers
reported in 2001 the first modification of the central aro-
matic core. The 2,4,6-trialkoxy-substituted BTA 11, referred
to as a “crowded arene”, was described as a new substance
forming mesomorphic materials (Figure 1, b).[8a,16] The in-
troduction of dodecyloxy chains into the 2-, 4- and 6-posi-
tions in 11 led to considerably stronger intermolecular
hydrogen bonds. Nuckolls and co-workers postulated that
1,3,5-tricarboxamides (BTAs)
1 form supramolecular
columnar-stacked structures[3] that show attractive material
properties.[4] The observation of discotic mesophases based
on the triamide structures has been attributed to the occur-
rence of π stacking[5] and to the simultaneous formation of
the maximum number of hydrogen bonds.[3,6] The hypothe-
ses used for rationalizing the material properties of BTAs
are based on X-ray structures of simpler crystalline models
and on modelling studies (see parts a,b of Figure 4 and
Supporting Information).[7]
The unexpected results obtained in the context of our
approach to creating novel addressable organic electronic
elements[9] induced us to undertake studies correlating ma-
terial properties with NMR experiments. The starting point
[a] Institut de chimie, Université de Neuchâtel,
Avenue Bellevaux 51, 2000 Neuchâtel, Switzerland
E-mail: Reinhard.Neier@unine.ch
http://www2.unine.ch/cho/page-7961.html
[b] NPAC, Université de Neuchâtel,
Avenue Bellevaux 51, 2000 Neuchâtel, Switzerland
[c] Institut de physique, Université de Neuchâtel,
Avenue Bellevaux 51, 2000 Neuchâtel, Switzerland
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500506.
Eur. J. Org. Chem. 2015, 5115–5127
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5115

C. Invernizzi, C. Dalvit, H. Stoeckli-Evans, R. Neier
FULL PAPER
the three additional substituents induced a conformational novel modified BTAs. We decided to study the assembly of
twist out of planarity. The formation of a columnar super- the two BTA derivatives 2 and 3. We present their synthesis
structure of crowded arenes by replacing the dodecyloxy (Scheme 1 and Scheme 2) and the analyses of their supra-
chains by phenylacetylene substituents has been reported molecular assembly in the liquid-crystalline and solid states
for compound 12 (Figure 1, b).[8b,17]
(see the Supporting Information). To elucidate the aggrega-
tion mechanism of 2 and 3, thermodynamic data in con-
junction with structural information were extracted by re-
cording their 1H NMR spectra in solution.[18] The two phe-
nomena invoked, hydrogen bonding and π stacking, should
1
be easy to detect by H NMR spectroscopy. The formation
of intermolecular hydrogen bonds induces a downfield shift
of the amide protons, whereas π stacking causes an upfield
shift of the aromatic protons.[19] NMR diffusion-ordered
spectroscopy (DOSY)[20] measures the changes in the dif-
fusion coefficient and allows evaluation of the formation
and size of supramolecular aggregates,[21] dendrimers[22]
and proteins.[23] The thermodynamic data, derived from
concentration-induced variations in the chemical shifts in
1H NMR experiments, give a readout of the sum of all the
forces in place during the aggregation process. The 2-substi-
tuted BTA scaffolds in 2 and 3 are compared with the C3-
symmetric BTA 1. A comparison of the relative capacities
of these molecules to form intramolecular hydrogen bonds
provides a measure of the influence of the alkynyloxy group
in 2 and of the sterically demanding bromine atom in 3 on
the aggregation process.
Results and Discussion
The choice of the introduction of an alkynyloxy group
was driven by the attractiveness of forming dimeric struc-
tures by “click chemistry”. Terminal triple bonds can be
selectively and efficiently transformed with the help of Cu-
catalysed azido-alkyne “click-chemistry” (CuAAC),[24]
a
strategy that has already been used by our group to form
mesogenic dimeric structures.[9b] The alkynyloxy substituent
can easily be introduced by phenol alkylation and varying
the alkyne derivative allows modulation of the length of the
linker. The study of the material and self-assembly proper-
ties of 2-bromo-substituted BTA 3 was envisaged for com-
parison reasons with a sterically demanding but non-
hydrogen-bonding substituent. The synthesis of the 2-alk-
ynyloxy-BTA scaffold was started from the previously re-
ported 2-methoxytrimesic acid (4; Scheme 1). Compound 4
was prepared according to the procedure reported by Ray-
mond and co-workers.[25] A permanganate-mediated oxid-
ation under basic conditions of 2,6-bis(hydroxymethyl)-p-
cresol furnished the 2-methoxy-triacid 4 in yields compar-
able to those reported in the literature. The triacid 4 was
converted into the corresponding triacyl chloride by em-
Figure 1. a) Supramolecular architectures of columnar-stacked tri-
alkylbenzene-1,3,5-tricarboxamide units 1 reported by Matsunaga
et al.[3] b) Supramolecular motif of “crowded arenes” 2,4,6-trisub-
stituted benzene-1,3,5-tricarboxamides 11 and 12 proposed by
Nuckolls and co-workers.[8] The introduction of three additional
substituents on the BTA skeleton strengthened the intermolecular
interactions and leads to a wider temperature range for the occur-
rence of the liquid crystalline phase. c) Tentatively proposed supra-
molecular structures of columnar-stacked BTA derivatives substi-
tuted in the 2-position. To apply the new BTA derived design we
had to explore the supramolecular assembly, the molecular proper-
ties of the novel structures and the influence of the introduction of
a single, disturbing substituent into the skeleton. In parts a–c, the
red dashed lines indicate intermolecular hydrogen bonds.
We proposed to introduce a single alkoxy group into the ploying 3 equivalents of thionyl chloride, which was then
aromatic scaffold to make a “minimal” structural change treated with an excess of primary amine. The corresponding
(Figure 1, c). The alkoxy group would be used as a linker amides 5 and 6 were isolated in good yields over two steps.
to create covalent linear dimers. To the best of our knowl-
The 2-methoxy-benzamides 5 and 6 were deprotected by
edge, no studies of 2-monosubstituted BTAs have been re- nucleophilic methyl ether cleavage according to the condi-
ported and we have characterized the mechanism of the tions reported by Chakraborti et al.,[26] employing the
self-aggregation and the structures of the aggregates of the potassium salt of thiophenol in N-methyl-2-pyrrolidone at
5116
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5115–5127

Self-Aggregation of 2-Substituted Benzene-1,3,5-Tricarboxamides
Scheme 1. Synthesis of 2-alkynyloxy-BTA derivatives 2 and 9.
150 °C. The final alkylation step of the phenol derivatives (–2.54 kJmol–1) at 64.1 °C associated with the transition
7 and 8 was found to be a difficult transformation. Mod- from the solid to the mesomorphic phase. A second exo-
ifying the reaction conditions led to moderate yields of the thermic phase transition (–2.14 kJmol–1) was observed at
products 2 and 9 (42 and 17%, respectively) when caesium 109.4 °C. The final isotropization (141.1 °C) was associated
as large carbocation in DMF was used. The electronic sta- with a strong exothermic transition with an enthalpy of
bilization of the phenoxide by conjugation coupled with the –5.09 kJmol–1. Three phase transitions were also measured
formation of intramolecular hydrogen bonds affected nega- in the cooling cycle. The isotropic liquid formed the meso-
tively the nucleophilicity and thereby the reactivity of 7 and morphic phase at 147.5 °C, showing a strong endothermic
8. Crystallographic evidence for these strong intramolecular transition (4.66 kJmol–1). The small endothermic transition
hydrogen-bonding interactions has been reported by Uey- (1.75 kJmol–1) at 120.3 °C indicated a change in the meso-
ama and co-workers in their study of the deprotonated form morphic organization and the final solidification of 2 at
of salicylamide derivatives.[27]
2-Bromo-BTA 3 was obtained in two steps starting from micity (2.49 kJmol–1).
57.0 °C was associated with a medium intense endother-
2-bromotrimesic acid (10), as described by Wallenfels et al.
(Scheme 2).[28] The triacid 10 was converted into 3 by using
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and
N-hydroxysuccinimide in DMF in an acceptable 18% yield.
The heating cycle of 3 presented a very small exothermic
peak (–0.48 kJmol–1) indicating the phase transition be-
tween the solid and mesomorphic phase at 70.8 °C. Two
other phase modifications were observed in the heating
cycle: a strong endothermic peak (18.86 kJmol–1) at 146.7 °C
followed by a strong exothermic peak (–20.8 kJmol–1) at
209.1 °C. These two transitions might indicate the forma-
tion of a partially organized structure during the heating
cycle (cold crystallization) and its relative melting. The final
isotropization of 3 was reached at 239.5 °C. In the cooling
cycle, the isotropic liquid underwent a phase transition
(9.00 kJmol–1) towards the mesomorphic phase at 245.2 °C
and the final solidification was observed at 69.5 °C, associ-
ated with a very small endothermicity (0.4 kJmol–1).
Scheme 2. Synthesis of 2-bromo-BTA derivative 3.
The temperature range of liquid crystallinity for 3 is
much larger than the range observed for 1 (Table 1). The
liquid crystallinity of 3 resembles that reported by Nuckolls
and co-workers for trialkoxy-substituted crowded derivative
Analyses in the Bulk
DSC Analysis
BTAs 2 and 3 were analysed by DSC, which revealed 11 (Table 1).[8a] The presence of an alkynyloxy group in 2
polymorphism and a liquid-crystalline mesophase over a considerably reduced the temperature range of liquid crys-
broad range of temperatures for both derivatives (Table 1; tallinity in comparison with BTAs 1 and 3. The enthalpies
for DSC traces, see the Supporting Information). The determined for the transitions of compound 2 resemble
heating cycle of
2 presented an exothermic peak those reported for compounds 1 and 11 forming columnar
Eur. J. Org. Chem. 2015, 5115–5127
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5117

C. Invernizzi, C. Dalvit, H. Stoeckli-Evans, R. Neier
Table 1. Transition temperatures[a] and, in parentheses, the relative enthalpies of different BTA derivatives.
FULL PAPER
BTA
Transition temp. [°C] (ΔH [kJmol–1])
1st cooling cycle
ΔT [°C][b]
2nd heating cycle
1[c]
2
99 (–12)
64.1 (–2.54) 109.4 (–2.14)
70.8 (–0.48) 146.7 (18.86) 209.1 (–20.8) 239.5 (–7.78)
98 (–57.1) 294 (–35.1)
205 (–22)
141.1 (–5.09)
106
77
168.7
196
147.5 (4.66) 120.3 (1.75) 57.0 (2.49)
3
245.2 (9.00)
247 (5.6)
69.5 (0.4)
83 (39.1)
11[d]
[a] The transition temperatures have an associated error of Ϯ0.2 °C.[b] Temperature range of liquid crystallinity calculated from the 2nd
heating cycle. [c] Transition temperatures and enthalpy, as reported by Matsunaga et al.[3] [d] Transition temperatures and enthalpies, as
reported by Nuckolls and co-workers.[8a]
liquid crystals. The presence of bromine increases the solid- (Table 2, Figure 4, c,d). All three measured amide torsion
like behaviour of 3, whereas the presence of the pentynyloxy angles Cortho–Cipso–C=O, for both independent molecules
group in 2 decreases its melting point and consequentially 9-α and 9-β in the crystal, show significant twisting from
its phase-transition energies. The enthalpies for the phase coplanarity. The conformation of the amide group in N-
transition of 2 are smaller than those for the reference com- alkylbenzamides is usually coplanar giving an optimal over-
pounds 1 and 11. In accordance with this data, the tempera- lap between the aromatic π system and the π orbitals of the
ture for the first observed transition is lower and, in paral- amide group (see the Supporting Information). One of the
lel, the range of liquid crystallinity is smaller.
N–H groups in the ortho position of 9 (N1 for α and N4
for β, Figure 3 and Figure 4, c,d) additionally forms an in-
tramolecular hydrogen bond with the oxygen of the pentyn-
yloxy group (Figure 3, magenta dashed lines; Figure 4, c,d,
red dashed lines; Figure 5 magenta dashed lines, see
Table 2).
Polarized Optical Microscopy
Polarized optical microscopy (POM) was carried out on
BTAs 2 and 3. Both BTAs 2 and 3 formed pseudo-conic
textures when cooled from their isotropic liquid phases
(Figure 2). These textures are characteristic of columnar li-
quid crystals. The DSC and POM analyses together indi-
cate that 2-substituted BTAs, such as 2 and 3, present sim-
ilar mesomorphic behaviour to the unsubstituted BTA 1
and the fully substituted 11.
Figure 2. POM micrographs at 100ϫ magnification of a) 2 at
137 °C and b) 3 at 202 °C.
Figure 3. Crystal structures of 9-α and 9-β. Hydrogen atoms have
been omitted for clarity. Red dashed lines indicate intermolecular
hydrogen bonds. Blue dashed lines indicate intramolecular
hydrogen bonds. Oxygen atoms are highlighted in red and nitrogen
atoms are highlighted in blue.
Single-Crystal X-ray diffraction
Chu and co-workers successfully crystallized the
The amides in the ortho position, not involved in intra-
N,NЈ,NЈЈ-trioctyl-BTA derivative reporting a chiral nano- molecular hydrogen bonds (N3 for α and N6 for β), show
sheet arrangement.[29] Unfortunately, compound 2 did not an unusually large torsion angle between the amide group
crystallize in our hands. By replacing the hexyl chains by and the plane of the aromatic ring (ca. 60°, twice as big as
ethyl groups (BTA 9, Scheme 1), crystals suitable for X-ray the other torsion angles, see Table 2). The occurrence of a
diffraction could be obtained by slow evaporation from larger dihedral angle on “crowded arenes” has already been
CDCl3. The ethyl-substituted BTA 9 crystallizes in a mono- postulated by Nuckolls and co-workers.[8a] Our crystallo-
clinic unit cell containing two independent molecules in the graphic results are in agreement with his hypothesis and
asymmetric unit (Figure 3, molecules α and β, Figure 4, c,d, molecular modelling calculations.
see the Supporting Information). All three secondary amide
The two ortho-amide groups point in the same direction
groups are involved in two intermolecular hydrogen bonds, (same sign of the dihedral angle) with respect to the plane
as confirmed by the measured C=O···H–N distances of the aromatic ring (same helicity of the propeller-like ar-
5118
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5115–5127

Self-Aggregation of 2-Substituted Benzene-1,3,5-Tricarboxamides
Figure 4. a) Structure of the model compound 13 reported by Lightfoot et al.[7a] and b) schematic representation of its X-ray structure.
All the carbonyl groups are oriented towards the same face with respect to the aromatic plane. c,d) Schematic representations of the X-
ray structures of 9-α and 9-β. The dihedral angles of the amide groups with respect to the main plane of the aromatic core are indicated.
Red dashed lines indicate intramolecular hydrogen bonds and black dashed lines indicate intermolecular hydrogen bonds.
rangement), whereas the para-amide group points in the op-
Table 2. Hydrogen bond lengths of molecules 9-α and 9-β.
posite direction. This switch of directionality of the amide
Molecule Donor
(N–H)
Acceptor
(C=O)
d [Å][a] Dihedral angle θ [°] [b]
groups is in contrast with the BTA model derivative 13 re-
ported in the literature, which forms columnar mesophases
(Figure 4, a,b, see the Supporting Information). The asym-
metric unit contains two independent molecules, α and β,
arranged in pseudo-sheets in the crystal lattice (Figure 5).
Both molecules have the maximum number of six intermo-
lecular hydrogen bonds each (Figure 5, blue and black
dashed lines). In addition to these intermolecular hydrogen
bonds, one intramolecular hydrogen bond is formed be-
tween one of the ortho-amide groups (N–H) and the oxygen
of the alkynyloxy group (see Table 2, Figure 5, magenta
dashed lines). Only two out of the six intermolecular
hydrogen bonds contribute to the sheet packing (NH5···O4
and NH2···O8, see Table 2 and Figure 5, blue dashed lines).
These intermolecular interactions generate dimeric aggre-
gates in which the molecules are almost coplanar (the intra-
planar dihedral angle is ca. 4°, see Figure 5 and the Sup-
porting Information). This arrangement allows π–π interac-
tions thereby potentially enabling columnar organizations.
The other four intermolecular interactions (Figure 5, black
dashed lines) are directed out of the sheet plane generating
an orthogonal packing that deviates from the potential co-
lumnar arrangement (no π–π stacking). The formation of
the intramolecular hydrogen bond perturbs the regular
growing of the sheet aggregates.
9-α
N1
O6
O8
O7
O2
O4
O3
2.10(3) C1–C6–C7–O2 –150.4(3)
1.94(3) C5–C4–C10–O3 30.3(4)
2.06(3) C3–C2–C13–O4 –113.7(3)
2.12(3) C23–C22–C27–O6 –30.6(4)
2.12(3) C25–C24–C30–O7 148.4(3)
2.07(3) C21–C26–C33–O8 –60.3(4)
N2[c]
N3
9-β
N4
N5[c]
N6
Intramolecular hydrogen bond
9-α
9-β
NH1
NH4
O1
O5
2.30(3) N1–H1–O1 119(2)[d]
2.27(3) N4–H4–O5 119(2)[d]
[a] The distance d refers to the H···O bond. [b] The sign of the
amide dihedral angles indicates the orientation of the carbonyl
(C=O) of the amide group with respect to the aromatic plane. For
a columnar assembly all of the amide groups have to be directed in
the same orientation, leading to the same helicity of the hydrogen-
bonding network. [c] This interaction generates a sheet arrange-
ment between the two independent molecules 9-α and 9-β. [d] Mea-
sured angle of the intramolecular hydrogen bond.
Despite the significant differences between the crystal
structure of 9 and the structure of the model BTA 13, a
liquid crystalline phase has been observed for 2. Therefore
an analysis of the thermodynamic parameters of the self-
assembly process in solution was needed to elucidate quan-
titatively the effect of the additional substituent on the for-
mation of intermolecular hydrogen bonds in an effort to
rationalize the differences found between 1, 2 and 3 in the
liquid-crystalline state.
Figure 5. X-ray structure of the pseudo-sheet formed by 9.
Hydrogen atoms have been omitted for clarity. Magenta dashed
lines refer to intramolecular hydrogen bonds and blue dashed lines
refer to intermolecular hydrogen bonds generating sheet aggrega-
tion. The dimer sheet aggregates, indicated by the same colour
(light green and light blue) arise exclusively from NH5···O4 and
NH2···O8 hydrogen bonds. Black dashed lines refer to intermo-
lecular hydrogen bonds generating quasi-orthogonal aggregates.
Eur. J. Org. Chem. 2015, 5115–5127
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5119

C. Invernizzi, C. Dalvit, H. Stoeckli-Evans, R. Neier
FULL PAPER
Analyses in Dilute Solution
was measured (Δδ ≈ 1.6 ppm) over the same concentration
1
range. A concentration-induced variation of the H NMR
1
chemical shift of BTA 2 was also observed at 295 K in
CD2Cl2 (Figure 7). The presence of the pentynyloxy substit-
uent on the aromatic ring causes a reduction of the sym-
metry of the molecule (C2v), generating two distinct signals
for the N–H group of the three amides. For the sake of
clarity, these signals are referred to as N–Hortho and N–
Variable-Concentration H NMR Dilution Experiments
1H NMR experiments were performed at different con-
centrations of 2 and 3 in [D2]dichloromethane as the sol-
vent to measure the association constant Ka. BTA 1 was
chosen as the reference compound. The association process
has been well studied and is described in the literature.[13b]
We chose [D2]dichloromethane to minimize the hydrogen-
bond-donor or -acceptor effects that occur with other sol-
vents such as CDCl3 or [D6]DMSO. The H NMR spectra
of BTA 1 were recorded at 295 K in a concentration range
varying from 0.39 to 202 mm (Figure 6).
Hpara, respectively (see Scheme 3). Increasing the concentra-
tion (from 0.77 to 198 mm) caused an upfield shift of the
aromatic protons (Δδ = 0.21 ppm) and a downfield shift of
both types of N–H protons (N–Hortho Δδ = 0.281 ppm, N–
Hpara Δδ = 0.59 ppm). The Δδ values are considerably
smaller than those observed for BTA 1. The Δδ values for
the N–Hortho and the C–H protons of the aromatic ring are
similar, whereas the Δδ value for the N–Hpara proton is
twice as large, but still almost a factor of four less than
that of BTA 1. The bromo-BTA derivative 3 has a very low
solubility in CD2Cl2 and we were forced to replace [D2]-
1
1
Figure 6. Variable-concentration H NMR spectra of 1 in CD2Cl2
at 295 K. The NMR spectra were recorded by decreasing the con-
centration from 202.3 to 0.395 mm. Only the aromatic region be-
tween 8.7 and 6.5 ppm is presented.
1
Figure 7. Variable-concentration H NMR spectra of 2 in CD2Cl2
Upon increasing the concentration, a large downfield
shift of the N–H signals (Δδ ≈ 2 ppm) was observed. On
at 295 K. The NMR spectra were recorded by decreasing the con-
centration from 198 to 0.77 mm. In the figure only the aromatic
the other hand, a large upfield shift of the aromatic protons region (8.5–6.0 ppm) is presented.
Scheme 3. Comparison of the different BTA structures 1–3. The reduced symmetry in 2-substituted BTA 2 and 3 generates two distinct
signals of the amide protons (N–Hortho and N–Hpara).
5120
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5115–5127

Self-Aggregation of 2-Substituted Benzene-1,3,5-Tricarboxamides
dichloromethane with [D1]chloroform. As in the case of ence of such an intramolecular hydrogen bond not only in
BTA 2, the N–H signals are referred to as N–Hortho and N– the pure material but also in solution.
Hpara (see Scheme 3). By increasing the concentration from
1H DOSY NMR Study
0.10 to 82 mm, a large upfield shift for the C–H protons (Δδ
To complete the analysis of the aggregation of our BTA
derivatives in solution, 1H 2D-DOSY experiments were exe-
cuted. As for the variable-concentration H NMR experi-
ments, BTA 1 was selected as the reference compound for
the 2D DOSY experiments and [D2]dichloromethane was
used as the solvent. For all three BTAs 1–3, a reduction of
the diffusion coefficient was observed upon increasing the
concentration (Figures 9–11 and Table 3).
= 0.95 ppm) was observed and a very large downfield shift
was observed for the N–H protons of the amides (N–Hortho
Δδ = 2.45 ppm, N–Hpara Δδ = 2.53 ppm, Figure 8). The Δδ
values for both types of N–H protons are even larger than
those observed for compound 1, whereas the Δδ value for
the aromatic C–H was almost a factor of two smaller than
the values observed for our reference compound. The NMR
spectra of 3 show extensive line-broadening at certain con-
centrations, probably due to the intermediate exchange rate
of the association of 3.
1
1
Figure 9. H 2D DOSY spectra of 1 in CD2Cl2 at a concentration
of 202.3 and 25.9 mm. The spectra were recorded at 295 K.
1
Figure 8. Variable-concentration H NMR spectra of 3 in CDCl3
at 295 K. The NMR spectra were recorded by decreasing the con-
centration from 82 to 0.10 mm. In the figure only the aromatic re-
gion (9.0–5.0 ppm) is presented. * The asterisks indicate the 13C
satellite signals of the residual CHCl3 in the NMR solvent.
Globally, the observed concentration-induced upfield
shifting of the aromatic protons is coherent with the en-
hancement of π–π interactions. According to the X-ray
structures of the model tris(2-methoxyethyl)-BTA derivative
13 (see the Supporting Information), the short inter-ring
distance (3.62 Å) enables strong aromatic interactions (π–π
stacking) along the columnar axis of the mesophase re-
sulting in an upfield ring-current shift of the aromatic pro-
tons. In the case of the amide protons, the observed concen-
tration-induced downfield shifting is consistent with the
formation of intermolecular hydrogen-bonding interactions.
The presence of a bulky atom, such as bromine, influences
the amide torsion angle. The carbonyls of the amides are
1
Figure 10. H 2D DOSY spectra of 2 in CD2Cl2 at 198 (in grey),
49.5 ⁽in red⁾, 6.18 ⁽in green⁾, and 0.772 mm (in blue) recorded at
295 K.
These results are consistent with the formation of supra-
forced out of planarity despite the concomitant loss of con- molecular aggregates, which diffuse more slowly than the
jugation. In the case of BTA 2, the concentration-induced monomeric species. In the DOSY spectrum of 13.7 mm of
shift of the N–Hortho protons is two-fold smaller than the 3, the signals of the amide protons are broad, whereas the
shifts of the N–Hpara proton and four-fold smaller than the aromatic proton signal partially overlaps with the residual
shifts observed for the reference compound 1. In an effort signal of CHCl3. These experimental difficulties hamper the
to explain this observation, we invoked the formation of precise measurement of the diffusion coefficient from these
intramolecular hydrogen bonds by the N–Hortho protons of signals. However, the diffusion coefficient of the molecule
2. The dilution experiments are compatible with the pres- can be measured from the analysis of the signals in the ali-
Eur. J. Org. Chem. 2015, 5115–5127
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5121

C. Invernizzi, C. Dalvit, H. Stoeckli-Evans, R. Neier
FULL PAPER
Figure 13. Curves fitted according to Equation (3) for the plot δ vs.
[2]. a) N–H protons: ᭹ indicate N–Hortho signals and ᭿ indicate
N–Hpara signals. b) C–H aromatic protons. In both curves the as-
ymptotes, indicating full aggregation, are not reached due to a
weakness of the binding.
Figure 11. 1H 2D DOSY spectra of 3 in CD2Cl2 at 41 and 13.7 mm.
The spectra were recorded at 295 K.
Table 3. Observed diffusion coefficients D for BTA 1–3 at different
concentrations.
BTA 1
BTA 2
BTA 3
[BTA][a] 202.3
25.9
198
49.5 6.18
0.772
–8.89
0.994
41
13.7
[b]
Dobs
–9.79
0.03
–9.19
–9.23 –9.08 –9.02
0.40 0.77 0.96
–9.46 –9.22
0.14 0.35
[c]
χmon
0.58[d]
[a] BTA concentrations in mmol/L. [b] Diffusion coefficients mea-
sured as log(m2 s–1). [c] The molar fractions of the monomer species
χmon were obtained based on the extrapolated limiting value (see
the Supporting Information) obtained from the fitting curves (see
Figures 12, 13 and 14). [d] Extrapolated values (see the Supporting
Information).
Figure 14. Curves fitted according to Equation (3) for the plot δ vs.
[3]. a) N–H protons: ᭹ indicate N–Hortho signals and ᭿ indicate
N–Hpara signals. b) C–H aromatic protons.
Assuming complete aggregation (χagg = 1) and complete
disaggregation (χmon = 1) at the two limits of the fitting
curves, an estimation of the ratio (molar fraction χ) of the
aggregate and the monomer can be obtained for the mea-
sured experimental points. The monomer molar fraction
χmon was calculated based on the measured shift of the N–
H signal. In the case of BTAs 2 and 3, the calculation was
carried out based on the shift of the N–Hpara signal being
exclusively due to intermolecular hydrogen-bonding inter-
actions (Table 3).
phatic region of the spectrum (Figure 11). The observed
chemical shift δobs is the weighted average of the chemical
shifts of the monomeric species (δmon) and the aggregated
species (δagg) according to Equation (1)
(1)
in which χmon and χagg are the fractions of monomer and
aggregate, respectively, and χmon + χagg = 1. Similarly, the
observed diffusion coefficient Dobs is the weighted average
of the diffusion coefficient of the monomer (Dmon) and the
aggregate (Dagg), respectively, according to Equation (2).
Simulation of the Aggregation Process
The concentration-induced chemical shifts were fitted ac-
cording to a non-linear least-squares equation. Meijer and
co-workers elaborated a fitting equation to interpolate iso-
desmic aggregation curves, specifically excluding cooper-
ativity.[30] However, BTA 1 is known to aggregate according
to a cooperative mechanism characterized by a nucleation
step (Kn) and an elongation step (Ke). Therefore the general
fitting procedure based on a logistic fitting function using
the OriginePro8® program[32] [δC–H and δN–H vs. [BTA],
Equation (3)] was used, giving a considerably better fit (cor-
relation coefficients above 0.99).
(2)
The limiting values of δmon and δagg can be extrapolated
from the curve fitting (Figure 12, 13 and 14).
(3)
In Equation (3), c is the total concentration of the BTA,
p is the slope factor of the fitting curve, δmon and δagg are,
Figure 12. Curves fitted according to Equation (3) for the plot δ vs.
[1]. a) N–H protons and b) C–H aromatic protons.
5122
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5115–5127

Self-Aggregation of 2-Substituted Benzene-1,3,5-Tricarboxamides
Table 4. Thermodynamic data for the aggregation of BTAs 1–3 calculated at 295 K by applying the logistic fitting equation and the isodesmic
fitting model.
Logistic[a]
BTA 1
BTA 2
N–Hpara
BTA 3
N–Hpara
N–H
C–H
N–Hortho
C–Harom.
N–Hortho
C–Harom.
Kd [mM]
34 (1)
29(4)
39 (2)
26(5)
196(53)
5(1)
176(30)
6(1)
337 (117)
3(1)
8.4(3)
119(4)
8.0(4)
125(6)
9.3(2)
108(2)
Ka [m–1]
R2
p
0.9985
1.8(1)
–8.3 (1)
0.9968
2.2(2)
–8.0 (1)
0.9998
0.91(4)
–4.0(7)
0.9999
0.94(3)
–4.3(4)
0.9999
0.90(4)
–2.7(9)
0.9994
1.22(5)
–11.7(1)
0.9993
1.16(5)
–11.8(1)
0.9998
1.19(3)
–11.5(1)
ΔG[d] [kJmol–1]
Isodesmic[b]
Ka [m–1]
R2
15(6)[c]
0.9728
–7(1)
10(5)[c]
0.9584
–6(1)
4.7(3)
0.9998
–3.8(2)
4.5(2)
0.9999
–4(1)
3.3(2)
0.9998
–2.9(1)
109(25)
0.9909
–11.5(6)
120(25)
0.9927
–11.7(5)
98(20)
0.9928
–11.3(5)
ΔG[d] [kJmol–1]
[a] Calculated from the fitting procedure using Equation (3). [b] Calculated from the fitting procedure using Equation (4). [c] The values
calculated for 1 by applying the isodesmic model have a low correlation coefficient (R2), which indicates low quality of fit. [d] Gibbs free
energy.
respectively, the extrapolated values of the chemical shifts from C–H) is compatible with the loss of one hydrogen-
for the monomer at infinite dilution and the chemical shift bonding interaction in 2.
for the aggregate obtained by the fitting procedure, and Kd
This observation supports the hypothesis that the forma-
(mmolL–1) is the dissociation constant of the aggregates. tion of an intramolecular hydrogen bond in 2 destabilizes
The association constants, measured as m–1, were calculated the columnar assembly, tentatively attributed to the occur-
based on the relation Ka = 1000/Kd. If p Ͼ 1, a sigmoidal rence of a competing intramolecular hydrogen bond. The
behaviour of the fitting curve is indicated that is compatible presence of bromine in 3 significantly stabilizes the colum-
with positive cooperativity, and if p Ͻ 1 negative cooper- nar association process. The large dihedral angle of at least
ativity is indicated. When p = 1, the curve assumes a hyper- one of the amide groups relative to the plane of the aro-
bolic behaviour, which indicates the absence of cooperativ- matic ring in BTA 3 may enhance the formation of intermo-
ity. This statistical data fitting was applied to the concentra- lecular hydrogen bonds. The increase in this dihedral angle
tion-dependent NMR data of 1. The best fit (Figure 12, has been invoked as an argument for the reinforced strength
a,b) gave a sigmoidal curve with positive cooperativity, as of the self-assembly.[8a] The slope factors obtained from the
indicated by the slope factor of 1.8(1) for N–H and of 2.2(2) fitting of the curves of the experimental data for 2 and 3
for C–H (Table 4). The result of the statistical data analysis gave p values close to 1 (Table 4), which indicates no or only
shows cooperativity for the aggregation of 1, in agreement small cooperativity. For compounds 2 and 3, the use of the
with the findings reported in the literature.[13b] As our isodesmic model [Equation (4)] for the fitting process gave
NMR results for 1 are compatible with the conclusion re- results that cannot be distinguished from the results ob-
ported in the literature, we deduced that our procedure is tained by the more general approach using logistic fit-
suitable for the analysis of the aggregation behaviour of ting.[30]
BTA derivatives. The values of Ka, 29 m–1 determined by
using the shifts of the N–H signals and 26 m–1 deduced by
using the shifts of the C–H aromatic signals, are, to all in-
(4)
tent and purposes, sufficiently similar such that we can as-
sume that the aggregation observed by monitoring the two
separate sensors is the same association process. The ob-
served association constants Ka for the three studied com-
pounds decrease in the order 3 Ͼ 1 Ͼ 2 (Table 4). The rela-
tive strength of the association constant Ka follows the same
trend as the material property expressed as the temperature
range of the liquid-crystalline phase observed by DSC
(Table 1).
As indicated, the application of Equation (4) to the
NMR data of 1 resulted in poorer data fitting due to the
cooperativity effects described (see Table 4 and the Sup-
porting Information).
Conclusions
The unsubstituted BTA 1 has been carefully studied and
The mono-core-functionalized BTA derivatives 2 and 3
characterized. Therefore we used BTA 1 as the reference form columnar mesophases over a broad temperature
compound in our studies. The association constant Ka of 2- range. By using the C3v-symmetric molecule 1 as a reference
pentynyloxy-BTA 2 is significantly smaller than that of 1 compound, the thermodynamics of the supramolecular as-
(about six- to eight-fold smaller). On the other hand, the sembly process could be analysed by a variable-concentra-
1
value of Ka determined for the association of 3 is four-fold tion H NMR analysis. Concentration-dependent chemical
larger than that of 1 (Table 4). The calculated difference in shifts together with the results of DOSY experiments al-
ΔG (ΔG = –RTlnKa) between 1 and 2 (4.3 kJmol–1 from lowed the determination of the thermodynamics of the sup-
the N–Hortho, 4.0kJmol–1 from N–Hpara and 5.3 kJmol–1 ramolecular aggregation process and differentiation be-
Eur. J. Org. Chem. 2015, 5115–5127
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5123

C. Invernizzi, C. Dalvit, H. Stoeckli-Evans, R. Neier
FULL PAPER
recorded with a Perkin–Elmer Spectrum One FT-IR version B
spectrophotometer using the Perkin–Elmer Spectrum™ 5 soft-
ware[33] for recording and treating the data. Peaks are reported in
cm–1 with relative intensities indicated as follows: s (strong, 67–
100%), m (medium, 34–66%) and w (weak, 0–33%). Solid samples
were measured in freshly prepared KBr pellets. Liquids were mea-
sured as films using polished KBr plates. Melting points were deter-
mined by using a Gallenkamp MPD 350-BM capillary melting-
point apparatus in open tubes. Analytical TLC was performed on
Merck silica gel plates [aluminium sheets pre-coated with silica (60
tween isodesmic and cooperative self-assembly. The intro-
duction of the pentynyloxy group, a hydrogen-bond-ac-
ceptor substituent, into the BTA derivative 2 reduced the
temperature range of the liquid crystalline phase and the
strength of the aggregation process in solution. Both of
these observations are compatible with the destabilization
of the supramolecular assembly, formed through intermo-
lecular hydrogen bonds, by the formation of an intramolec-
ular hydrogen-bonding interaction. The introduction of
bromine onto the BTA aromatic core efficiently stabilized F254)] or on Merck aluminium oxide plates [aluminium sheets pre-
coated with aluminium oxide (60 F254)]. Visualization was ac-
complished with UV light unless noted otherwise. Flash column
chromatography was performed by using silica gel (Brunschwing
Silica gel 60, 32–63 or Brunschwing Silica gel 60, 63–200). All reac-
tion temperatures refer to oil bath temperatures measured with
Heidolph EKT 3 mA® thermocouples unless specifically men-
tioned otherwise. DSC analyses were accomplished with a Mettler
Toledo DSC1 STARe® instrument. The samples were prepared in
an aluminium sampler. Each analysis refers to three heating–cool-
ing cycles performed at 10 °Cmin–1 under nitrogen flux. The re-
ported temperatures refer to the “onset” peak. Data were analysed
by using STARe software. POM analyses were performed with an
Axio Scope Zeiss microscope. Samples were heated on a Linkam
THMS600® heater controlled by a Linkam 93 apparatus. POM
images were taken by using a Fujix Digital Camera HC-300Z® and
processed with the AxioVision Rev 4.8® program.
the columnar organization and increased the strength of the
aggregation in solution. In both cases, the functionalization
of the aromatic core induced the loss of cooperativity dur-
ing the supramolecular assembly process. The BTA deriva-
tives 2 and 3 were found to aggregate according to an iso-
desmic self-assembly process.
Experimental Section
General: Reactions requiring anhydrous conditions were performed
in oven-dried (120 °C) glassware under dry N2 or dry Ar. An-
hydrous solvents such as toluene (Ն99.7%, Յ0.005% H2O), DMF
(Ն99.8%, Յ0.01% H2O), DMSO (Ն99.5%, Յ0.005 H2O), THF
(Ն99.5%, Յ0.025 H2O, stabilized with 0.025% 2,6-di-tBu-4-meth-
ylphenol) were obtained from Aldrich and stored over molecular
sieves. N-Methylpyrrolidone (NMP) was purchased from Acros
(purity 99%). Brine refers to a satd. aq. solution of NaCl. Petro-
leum ether refers to the boiling fraction of 40–60 °C. All other sol-
vents were of technical grade and used without further purifica-
tions. 1H and 13C NMR spectra were recorded with Bruker Avance
II-400 (400.13 MHz, 1H; 100.61 MHz, 13C) and DPX 400
N1,N3,N5-Trihexylbenzene-1,3,5-tricarboxamide (1): Benzene-1,3,5-
tricarbonyl trichloride (1 g, 3.77 mmol) was dissolved in dry THF
(6 mL) and the solution was added dropwise to a solution of hex-
ylamine (2.3 mL, 30.1 mmol) in dry THF (6 mL) at 0 °C under
nitrogen. The reaction mixture was stirred at 0 °C for 30 min and
at room temperature for another 18 h. The organic solvent was
removed under vacuum and the crude solid was diluted with 2 m
HCl (15 mL). The product was extracted with ethyl acetate. The
resulting organic solution was washed again with 2 m HCl, 5% sol.
of NaHCO3 and brine. The organic phase was dried with MgSO4
and the solvent was removed under vacuum. The product was puri-
fied by chromatography on silica gel using cyclohexane/ethyl acet-
ate (1:1) as eluent to afford 1.125 g of 1 as an amorphous white
solid in 65% yield. Rf (SiO2, cyclohexane/ethyl acetate, 1:1) = 0.55.
1H NMR (CDCl3 400 MHz, 295 K): δ = 8.32 (s, 3 H, Ar-H), 6.56
1
(400.13 MHz, H; 100.61 MHz, 13C) spectrometers at the Neuchâ-
tel Platform of Analytical Chemistry (NPAC) of the University of
Neuchâtel. Chemical shifts (δ) are quoted in ppm and are given
relative to tetramethylsilane (δ = 0 ppm) as the internal standard
or the residual solvent peak of CDCl3 (δ = 7.26 ppm, 1H; δ =
77.0 ppm, 13C), dichloromethane (δ
= δ =
5.32 ppm, 1H;
53.84 ppm, 13C), methanol (δ = 3.31 ppm, 1H; δ = 49.00 ppm, 13C),
DMSO (δ = 2.50 ppm, 1H; δ = 39.52 ppm, 13C). All the deuteriated
NMR solvents were purchased from Cambridge Isotope. Multi-
plicities are indicated by s (singlet), d (doublet), t (triplet), q (quar-
tet), m (multiplet) and br. (broad). Coupling constants, J, are re-
ported in Hz. The assignments were verified by the following 2D
experiments if necessary: HSQC, HMBC and COSY. 1H 2D-COSY
experiments were performed by stimulated echo and LED schemes
using bipolar gradient pulses for diffusion and two spoil gradients.
The strength of the diffusion gradients was varied from 5 to 95%
in 32 increments. Typically, 8 to 32 scans were recorded for each
increment.[31] The lengths of the diffusion and spoil gradients were
2 and 1.1 ms, respectively, with a gradient recovery time of 200 μs.
The data matrix was 4Kϫ32 in the time domain and 4Kϫ512 in
the processed domain. Mass spectrometry was performed at the
NPAC of the University of Neuchatel. Electrospray [ESI (+/–)] MS
was performed with an API 4000 QTrap ABSciex or LC/MSD Trap
Agilent spectrometer. The LC–MS retention times (Rt) and low-
resolution MS were recorded with a UPLCUltimate 3000 Dionex –
API 4000 QTrap, ABSciex instrument. The solvents were of UPLC
3
3
(t, JH,H = 4.5 Hz, 3 H, NH), 3.45 (q, JH,H = 6.7 Hz, 6 H,
3
CH2NH), 1.60 (quint., JH,H = 7.2 Hz, 6 H, CH2CH2NH), 1.39–
1.31 (m, 18 H, CH2), 0.89 (t, JH,H = 6.5 Hz, 9 H, CH3) ppm. 13C
3
NMR (CDCl3, 100 MHz, 295 K): δ = 165.8, 135.4, 128.1, 40.5,
31.6, 29.6, 26.8, 22.7,14.2 ppm.
2-Methoxybenzene-1,3,5-tricarboxyilic Acid (4): Compound 4 was
prepared according to the procedure previously reported by Ray-
mond and co-workers.[27] 2,6-Bis(hydroxymethyl)-4-methylphenol
(10 g, 59.4 mmol) was dissolved in acetone (200 mL). Anhydrous
K2CO3 (12.32 g, 89.175 mmol) was added and the suspension was
stirred for 5 min. Me2SO4 (6.8 mL, 71.3 mmol) was added and the
reaction was stirred at 70 °C for 15 h. The solid was filtered off and
the solvent evaporated under vacuum to afford a crude white solid
product. The product was purified by recrystallization from ethyl
acetate to afford 6.4 g of a white solid in 60% yield. Rf (SiO2, ethyl
acetate/petroleum ether, 9:1) = 0.57, m.p. 107 °C. 1H NMR (CDCl3
400 MHz, 295 K): δ = 7.14 (s, 2 H, Ar-H), 4.71 (s, 4 H, CH2), 3.84
grade and water was Milli-Q® grade. High-resolution mass spectra (s, 3 H, OMe), 2.32 (s, 3 H, Me), 1.94 (s, 2 H, OH) ppm. 13C NMR
were recorded with a Bruker FTMS 4.7T BioAPEX II FT/ICR
spectrometer by using a standard electrospray ion (ESI) or MALDI
source at the University of Fribourg (Switzerland). IR spectra were
(CDCl3, 100 MHz, 295 K): δ = 165.8, 153.8, 134.3, 133.5, 124.3,
115.9, 62.2, 60.9, 20.8 ppm. MS (ESI): m/z (%) = 205.0 (100) [M +
Na]+.
5124
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5115–5127

Self-Aggregation of 2-Substituted Benzene-1,3,5-Tricarboxamides
KOH caps (3.8 g, 67.9 mmol) were added to a solution of (2-meth-
oxy-5-methyl-1,3-phenylene)dimethanol (6.18 g, 33.9 mmol) in dis-
tilled water (400 mL) and the mixture was stirred for 10 min.
KMnO4 (26.83 g, 169.7 mmol) was added portionwise and further
distilled water (200 mL) was added. The dark solution was stirred
at 100 °C for 7 h. The reaction mixture was cooled to room tem-
perature and Na2S2O3 powder was added until the permanganate
was reduced forming a dark-brown suspension. The solid residue
was filtered off and the volume of water was reduced to 150 mL by
distillation under vacuum. Concentrated HCl (37%) was added un-
til pH 3. The aqueous phase was saturated by adding solid NaCl.
The aqueous solution was extracted with AcOEt (4ϫ 200 mL). The
organic phases were dried with MgSO4 and the solvent was re-
moved under vacuum. The resulting white solid was dissolved in
methanol and the yellowish insoluble solid was filtered off. The
solvent was evaporated under vacuum to afford 6.2 g of 4 as a white
solid in 76% yield. The crude product was used without further
purification. 1H NMR (DMSO, 400 MHz, 295 K): δ = 8.31 (s, 2
H, Ar-H), 3.85 (s, 3 H, OMe) ppm. 13C NMR (DMSO, 100 MHz,
295 K): δ = 166.6, 166.0, 161.7, 134.8, 128.1, 126.1, 63.5 ppm. MS
(ESI): m/z (%) = 239.1 (100) [M – H]–.
to afford 207.3 mg of 7 as a yellowish solid in 61% yield. Rf (SiO2,
ethyl acetate) = 0.52, m.p. 187–190 °C. IR (KBr): ν = 3382 (w),
˜
3291 (m), 3067 (w), 2975 (w), 2934 (w), 2344 (vw), 1663 (s), 1630
(s), 1579 (s), 1541 (s), 1459 (s), 1336 (m), 1285 (s), 1196 (m), 1146
1
(m), 1062 (w), 936 (w), 800 (w), 769 (w), 692 (w) cm–1. H NMR
(CD3OD, 400 MHz, 295 K): δ = 8.45 (s, 2 H, Ar-H), 3.45 (q, 3JH,H
3
= 7.3 Hz, 4 H, CH2-NH), 3.41 (q, JH,H = 7.3 Hz, 2 H, CH2-NH),
3
3
1.25 (t, JH,H = 7.2 Hz, 6 H, CH3-CH2), 1.23 (t, JH,H = 7.2 Hz, 3
H, CH3-CH2) ppm. 13C NMR (CD3OD, 100 MHz, 295 K): δ =
168.7 (C=Oortho), 168.3 (C=Opara), 163.6 (C-OH), 132.8 (Ar), 126.2
(C-C=Opara), 119.4 (C-C=Oortho), 35.9 (CH2-NH), 35.7 (CH2-NH),
14.9 (CH3-CH2), 14.8 (CH3-CH2) ppm. MS (ESI): m/z (%) = 330.3
(100) [M + Na]+. HRMS (ESI): calcd. for C15H21N3O4Na+
330.1424; found 330.1427 [M + Na]+.
N1,N3,N5-Triethyl-2-(pent-4-ynyloxy)benzene-1,3,5-tricarboxamide
(9): N1,N3,N5-Triethyl-2-hydroxybenzene-1,3,5-tricarboxamide (7;
212 mg, 0.69 mmol) was dissolved in dry DMF (2 mL) in a vial
under N2. Cs2CO3 (226.9 mg, 0.69 mmol) and NaI (51.7 mg,
0.35 mmol) were added and the suspension was stirred for 5 min at
room temperature. 5-Chloro-1-pentyne (0.146 mL, 141.5 mg,
1.38 mmol) was added and the vial was sealed with a Teflon®-
coated cap and stirred at 60 °C for 48 h. The reaction was cooled
to room temperature and diluted with water. The solution was ex-
N1,N3,N5-Triethyl-2-methoxybenzene-1,3,5-tricarboxamide (5): 2-
Methoxybenzene-1,3,5-tricarboxylic acid (4) (500 mg, 2.1 mmol)
was suspended in dry toluene (5 mL) and SOCl2 (0.53 mL, tracted with ethyl acetate and the organic phases were dried with
7.3 mmol) and 2 drops of DMF were added. The suspension was
heated at 110 °C for 2 h. The resulting yellowish solution was
cooled to room temperature and the volatile compounds were re-
moved under high vacuum to furnish a pale-yellow oil. The re-
sulting acid chloride was dissolved in THF (5 mL) and added drop-
wise to a solution of EtNH2 (1.15 mL, 14.46 mmol, 70% sol. in
water) dissolved in THF (5 mL) at 0 °C. After the complete ad-
dition, the reaction mixture was stirred at 0 °C for 1 h and at room
temperature for another 4 h. The solution was acidified to pH 3 by
adding 2 m HCl. The organic solvent was removed under vacuum
and the resulting aqueous solution was diluted with water. The
product was extracted with ethyl acetate. The organic phase was
dried with MgSO4 and the solvent removed under vacuum. The
product was purified by chromatography on SiO2 using ethyl acet-
ate/methanol (8:2) as eluent to afford 429 mg of 5 as a white solid
in 64% yield. Rf (ethyl acetate/MeOH, 9:1) = 0.5, m.p. 167–168 °C.
MgSO4. The solvent was removed under vacuum and the product
was purified by chromatography on SiO2 using ethyl acetate (100%)
to furnish 43 mg of 9 as a white solid in 17% yield. Suitable crystals
for X-ray diffraction were obtained by slow evaporation from
CDCl3. Rf (SiO2, ethyl acetate) = 0.15, m.p. 147–148 °C. IR (film
CDCl ): ν = 3260 (m), 3074 (w), 2974 (w), 2935 (w), 2877 (w), 1639
˜
3
(s), 1539 (s), 1448 (m), 1381 (w), 1356 (w), 1297 (m), 1149 (w), 1029
(w), 665 (w) cm–1. 1H NMR (CDCl3, 400 MHz, 295 K): δ = 8.26
(s, 2 H, Ar-H), 7.18 (t, 3JH,H = 5.0 Hz, 2 H, NHortho), 6.46 (t, 3JH,H
3
= 4.9 Hz, 2 H, NHpara), 4.12 (t, JH,H = 6.5 Hz, 2 H, ArO-CH2-
3
CH2-CH2), 3.53–3.42 (m, 6 H, CH2-NH), 2.37 (dt, JH,H = 6.9,
4JH,H = 2.6 Hz, 2 H, CH2-CH2-C-CH), 2.03–1.96 (m, 3 H, O-CH2-
3
CH2-CH2-, Alkyne-CH), 1.26 (t, JH,H = 7.3 Hz, 6 H, CH3-CH2),
3
1.22 (t, JH,H = 7.3 Hz, 3 H, CH3-CH2) ppm. 13C NMR (CDCl3,
100 MHz, 295 K): δ = 165.5 (C=Opara), 164.9 (C=Oortho), 156.6 (C-
O), 131.9 (Ar), 131.0 (C-C=Opara), 129.2 (C-C=Oortho), 82.6 (C-
IR (KBr): ν = 3272 (m), 3077 (w), 2977 (m), 2937 (m), 1714 (m), CH), 75.7 (ArO-CH2-CH2-CH2-), 69.8 (Alkyne-CH), 35.2 (CH2-
˜
1644 (s), 1543 (s), 1465 (m), 1300 (s), 1149 (m), 1093 (m), 1057 NH), 35.1 (CH2-NH), 29.0 (ArOCH2-CH2-CH2-), 15.3 (-CH2-
1
(w), 1003 (m), 924 (w), 656 (w), 601 (w) cm–1. H NMR (CD3OD, CH2-C-CH), 14.89 (CH3-CH2), 14.86 (CH3-CH2) ppm. MS (ESI):
400 MHz, 295 K): δ = 8.15 (s, 2 H, Ar-H), 3.90 (s, 3 H, OCH3), m/z (%) = 396.5 (100) [M + Na]+ 769.8 (87) [2M + Na]+. HRMS
3
+
3.47–3.37 (m, 6 H, CH2-NH), 1.25 (t, JH,H = 7.3 Hz, 6 H,
(MALDI-TOF): calcd. for C20H27N3NaO4 396.1894; found
CH3ortho), 1.22 (t, JH,H = 7.3 Hz, 3 H, CH3para) ppm. 13C NMR 396.1885 [M + Na]+.
3
(CD3OD, 100 MHz, 295 K): δ = 168.0 (C=Oortho), 167.7 (C=Opara),
N1,N3,N5-Trihexyl-2-methoxybenzene-1,3,5-tricarboxamide (6): 2-
159.0 (C-OMe), 131.9 (Ar), 131.2 (C-C=Opara), 131.0 (C-C=Oortho),
63.3 (OCH3), 35.9 (CH2-NH), 35.8 (CH2-NH), 14.8 (CH3-CH2),
14.7 (CH3-CH2) ppm. MS (ESI): m/z (%) = 344.3 (100) [M +
Na]+. HRMS (ESI): calcd. for C16H23N3O4Na+ 344.1581; found
344.1575 [M + Na]+.
Methoxybenzene-1,3,5-tricarboxylic acid (4) (1.31 g, 5.46 mmol)
was suspended in dry toluene (15 mL). SOCl2 (1.4 mL,
19.09 mmol) and 5 drops of DMF were added. The reaction mix-
ture was stirred at 110 °C for 2 h. Volatile compounds were re-
moved under high vacuum to afford a yellowish oil. The oil was
N1,N3,N5-Triethyl-2-hydroxybenzene-1,3,5-tricarboxamide
(7): dissolved in dry THF (10 mL) and added dropwise to a solution
(5;
N1,N3,N5-Triethyl-2-methoxybenzene-1,3,5-tricarboxamide
of hexylamine (5 mL, 37.8 mmol) in dry THF (10 mL) at 0 °C. The
reaction mixture was stirred at 0 °C for 1 h and then for 15 h at
room temperature. The organic solvent was removed under vacuum
357 mg, 1.11 mmol) was dissolved in N-methyl-2-pyrrolidone
(3 mL). Thiophenol (0.11 mL, 1.11 mmol) and anhydrous K2CO3
(184.2 mg, 1.3 mmol) were added and the solution was stirred at and the resulting crude solid was dissolved in ethyl acetate and
150 °C for 2 h. The reaction mixture was cooled to room tempera-
ture and diluted with water. The resulting solution was acidified to
pH 5 by adding 2 m HCl and the product was extracted with ethyl
acetate. The organic phase was dried with MgSO4 and the solvent
was removed under vacuum. The product was purified by
chromatography on silica gel using ethyl acetate (100%) as eluent
washed with 2 m HCl, a 5% sol. of NaHCO3 and brine. The or-
ganic phase was dried with MgSO4 and the solvent was removed
under vacuum. The product was purified by chromatography on
silica gel by using ethyl acetate/toluene (1:1) to afford 1.729 g of 6
as a white amorphous solid in 64% yield. Rf (SiO2, ethyl acetate/
toluene, 1:1) = 0.36, m.p. 155.5 °C (DSC). IR (CDCl3 film): ν =
˜
Eur. J. Org. Chem. 2015, 5115–5127
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5125

C. Invernizzi, C. Dalvit, H. Stoeckli-Evans, R. Neier
FULL PAPER
3256 (m), 3076 (w), 2958 (s), 2931 (s), 2859 (m), 2245 (w), 1635 (s),
= 2.6 Hz, 2 H, CH2-CH2-C-CH), 2.01–1.93 (m, 3 H, O-CH2-CH2-
1549 (s), 1468 (m), 1423 (w), 1379 (w), 1273 (w), 1122 (vw), 1005 CH2-, Alkyne-CH), 1.63–1.53 (m, 6 H, NH-CH2-CH2-), 1.41–1.27
(w), 908 (s), 735 (s), 649 (w) cm–1. 1H NMR (CDCl3, 400 MHz, (m, 18 H, 3ϫ6 CH2), 0.90–0.85 (m, 9 H, CH3) ppm. 13C NMR
3
295 K): δ = 8.24 (s, 2 H, Ar-H), 7.32 (t, JH,H = 5.5 Hz, 2 H, (CDCl3, 100 MHz, 295 K): δ = 165.5 (C=Opara), 165.0 (C=Oortho),
NHortho); 6.52 (t, 3JH,H = 5.5 Hz, 1 H, NHpara), 3.88 (s, 3 H, OMe),
3.42 (q, JH,H = 6.9 Hz, 4 H, CH2-NH), 3.38 (q, JH,H = 6.9 Hz, 2
156.5 (C-O), 131.8 (Ar), 131.0 (C-C=Opara), 129.2 (C-C=Oortho),
82.6 (C-CH), 75.7 (O-CH2-CH2-CH2-), 69.7 (Alkyne-CH), 40.4
3
3
H, CH2-NH), 1.63–1.53 (m, 6 H, NH-CH2-CH2-), 1.39–1.23 (m, (CH2-NH), 40.3 (CH2-NH), 31.6 (CH2), 29.7 (NH-CH2-CH2-),
18 H, 9 CH2), 0.90–0.85 (m, 9 H, CH3) ppm. 13C NMR (CDCl3, 28.9 (OCH2-CH2-CH2-), 26.9 (CH2), 26.8 (CH2), 22.68 (CH2),
100 MHz, 295 K): δ = 165.6 (C=Opara), 164.8 (C=Oortho), 157.7 (C- 22.67 (CH2), 15.3 (-CH2-CH2-C-CH), 14.1 (CH3-CH2) ppm. MS
O), 132.0 (Ar), 131.1 (C-C=Opara), 128.7 (C-C=Oortho), 63.3 (OMe),
(ESI): m/z (%) = 564.6 (100) [M + Na]+. HRMS (MALDI-TOF):
40.4 (CH2-NH), 40.2 (CH2-NH), 31.6 (CH2), 29.61 (NH-CH2- calcd. for C32H51N3NaO4 564.3772; found 564.3773 [M + Na]+.
CH2-), 29.56 (NH-CH2-CH2-), 26.85 (CH2), 26.77 (CH2), 22.68
+
2-Bromobenzene-1,3,5-tricarboxylic Acid (10): Compound 10 was
synthesized according to the procedure reported by Wallenfels et
al.[29] 2-Bromomesitylene (2.6 g, 13.07 mmol) was dissolved in a
mixture of tert-butyl alcohol (150 mL) and distilled water
(350 mL). K2CO3 (5.42 g, 39.21 mmol) was added and the solution
was stirred for 5 min. KMnO4 (20.65 g, 130.7 mmol) was slowly
added and the dark-violet solution was stirred at 100 °C for 9 h.
The reaction mixture was then cooled to room temperature and the
excess permanganate was reduced by slowly adding solid Na2S2O3.
The brown solid was filtered off and tert-butyl alcohol was removed
by distillation under rotatory evaporation. The aqueous solution
was acidified with concentrated HCl (37%) until pH 3, saturated
with solid NaCl and extracted with ethyl acetate. The organic
phases were dried with MgSO4 and the solvent was removed under
vacuum. The white solid obtained was washed with dichlorometh-
ane to afford 2.3 g of 10 as a white solid in 62% yield. The crude
product was used without further purifications, m.p. 275–276 °C.
(CH2), 22.66 (CH2), 14.1 (CH3) ppm. MS (ESI): m/z (%) = 512.5
(100) [M + Na]+. HRMS (ESI): calcd. for C28H47N3O4Na+
512.3459; found 512.3435 [M + Na]+.
N1,N3,N5-Trihexyl-2-hydroxybenzene-1,3,5-tricarboxamide (8):
N1,N3,N5-Trihexyl-2-methoxybenzene-1,3,5-tricarboxamide (6;
1.7 g, 3.47 mmol) was dissolved in N-methyl-2-pyrrolidone (8 mL).
Thiophenol (0.35 mL, 3.47 mmol) and anhydrous K2CO3
(575.8 mg, 4.16 mmol) were added and the reaction mixture was
stirred at 150 °C for 2 h. It was then cooled to room temperature
and diluted with water. The solution was acidified to pH 3 by add-
ing concentrated HCl (37 %). The product was extracted with
dichloromethane. The organic phases were dried with MgSO4. The
solvent was removed under vacuum and the product was purified
by chromatography on silica gel using cyclohexane/ethyl acetate
(6:4) as eluent to afford 1.287 g of 8 as yellowish amorphous solid
in 78% yield. Rf (SiO2, cyclohexane/ethyl acetate, 6:4) = 0.49, m.p.
54 °C. IR (liquid film): ν = 3306 (m), 3081 (w), 2957 (s), 2930 (s),
˜
IR (solid KBr): ν = 3075 (m), 1699 (s), 1385 (w), 1284 (w), 1241
˜
2858 (m), 1634 (s), 1579 (s), 1542 (s), 1464 (s), 1415 (w), 1378 (w),
1287 (m), 1194 (w), 1149 (w), 1063 (vw), 932 (w), 806 (w), 768 (w),
727 (w), 674 (w) cm–1. 1H NMR (CDCl3, 400 MHz, 295 K): δ =
8.57 (s, 2 H, Ar-H), 7.88 (br., 2 H, NHortho), 6.61 (t, 3JH,H = 5.2 Hz,
1 H, NHpara), 3.47–3.37 (m, 6 H, CH2-NH), 1.63–1.52 (m, 6 H,
NH-CH2-CH2-), 1.37–1.26 (m, 18 H, 9 CH2), 0.90–0.85 (m, 9 H,
CH3) ppm. 13C NMR (CDCl3, 100 MHz, 295 K)*: δ = 166.6
(C=Opara), 163.2 (C=Oortho), 131.9 (C-C=Opara. C-C=Oortho)**,
124.7 (Ar), 40.5 (CH2-NH), 40.1 (CH2-NH), 31.61 (CH2), 31.58
(CH2), 29.6 (NH-CH2-CH2-), 29.3 (NH-CH2-CH2-), 26.81 (CH2),
26.79 (CH2), 22.6 (CH2), 14.1 (CH3) ppm. MS (ESI): m/z (%) =
499.0 (100) [M + Na]+. HRMS (ESI): calcd. for C27H45N3O4Na+
498.3302; found 498.3300 [M + Na]+. * C-O aromatic signal was
not detected. ** Very broad signal.
1
(m), 1033 (w), 922 (w), 763 (w), 674 (w) cm–1. H NMR (DMSO,
400 MHz, 295 K): δ = 8.15 (s, 2 H, Ar-H) ppm. 13C NMR (DMSO,
100 MHz, 295 K): δ = 167.0 (C=Oortho), 165.4 (C=Opara), 137.1 (C-
Br), 131.0 (Ar), 130.3 (C-C=Oortho), 121.6 (C-C=Opara) ppm.
2-Bromo-N1,N3,N5-trihexylbenzene-1,3,5-tricarboxamide (3): 2-
Bromobenzene-1,3,5-tricarboxylic acid (10; 80 mg, 0.277 mmol)
was dissolved in dry DMF (3 mL) and cooled to 0 °C under nitro-
gen. EDC·HCl (191.2 mg, 0.997 mmol) and N-hydroxysuccinimide
(127.5 mg, 1.108 mmol) were added and the murky solution was
stirred at 0 °C for 5 min. A solution of hexylamine (0.128 mL,
0.969 mmol) dissolved in dry DMF (2 mL) was slowly added to the
reaction at 0 °C. The reaction was stirred for 15 min at 0 °C and
then at 45 °C for 18 h. The reaction mixture was diluted with ethyl
acetate (15 mL) and the organic phase was washed with 2 m HCl
(2ϫ 15 mL), 10% Na2CO3 (2ϫ 10 mL) and brine (1ϫ 15 mL).
The organic phase was dried with MgSO4 and the solvent was re-
N1,N3,N5-Trihexyl-2-(pent-4-ynyloxy)benzene-1,3,5-tricarboxamide
(2): N1,N3,N5-Trihexyl-2-hydroxybenzene-1,3,5-tricarboxamide (8;
610 mg, 1.28 mmol) was dissolved in dry DMF (2 mL) in a vial.
KI (212 mg, 1.28 mmol) and anhydrous Cs2CO3 (424 mg, moved under reduced pressure. The product was purified by
1.28 mmol) were added and the suspension was stirred for 5 min at
room temperature. 5-Chloro-1-pentyne (0.41 mL, 3.85 mmol) was
then added and the vial was sealed with a Teflon®-coated cap and
stirred at 70 °C for 48 h and for another 48 h at room temperature.
The reaction was diluted in water and the solution was extracted
with ethyl acetate. The organic phases were dried with MgSO4 and
the solvent was removed under vacuum. The product was purified
by chromatography on silica gel using cyclohexane/ethyl acetate
(6:4) as eluent to furnish 292 mg of 2 as a colourless solid in 42%
yield. Rf (SiO2, cyclohexane/ethyl acetate, 6:4) = 0.46, m.p. 141.1 °C
chromatography on silica gel using toluene/ethyl acetate (4:6) as
eluent to afford 27 mg of 3 as a white solid in 18% yield. Rf (SiO2,
toluene/AcOEt, 4:6) = 0.42, m.p. 239.5 °C (see Table 1). IR (KBr):
ν = 3271 (m), 3081 (w), 2957 (m), 2929 (m), 2857 (m), 1639 (s),
˜
1553 (s), 1467 (m), 1378 (w), 1304 (w), 1149 (w), 1028 (w), 908 (w),
1
726 (w) cm–1. H NMR (CDCl3, 400 MHz, 295 K, c = 20 mm)*: δ
= 8.06 (s, 1 H, NHpara), 7.71 (s, 2 H, NHortho), 7.12 (s, 2 H, Ar-H),
3.32–3.29 (m, 6 H, CH2-NH), 1.63–1.56 (m, 6 H, NH-CH2-CH2-),
1.36–1.25 (m, 18 H, 3ϫ6 CH2), 0.93–0.88 (m, 9 H, CH3) ppm. 13
C
NMR (CDCl3, 100 MHz, 295 K, c = 20 mm)**: δ = 167.3 (C=O),
138.5 (C-Br), 127.9 (Ar), 40.6 (CH2-NH), 40.3 (CH2-NH), 31.7
(CH2), 29.3 (NH-CH2-CH2-), 27.0 (CH2), 26.9 (CH2), 22.8 (CH2),
(see Table 1). IR (KBr): ν = 3246 (m), 3079 (w), 2930 (m), 2859
˜
(m), 1634 (s), 1552 (s), 1451 (m), 1376 (w), 1297 (m), 1033 (w), 915
(w), 725 (w) cm–1. 1H NMR (CDCl3, 400 MHz, 295 K): δ = 8.25 14.2 (CH3) ppm. MS (ESI): m/z (%) = 560.7 (100) [M + Na]+, 562.6
(s, 2 H, Ar-H), 7.17 (t, 3JH,H = 5.6 Hz, 2 H, NHortho), 6.44 (t, 3JH,H (100) [M
+
Na]+. HRMS (MALDI-TOF): calcd. for
3
+
= 5.6 Hz, 2 H, NHpara), 4.11 (t, JH,H = 6.5 Hz, 2 H, O-CH2-CH2- C27H45BrN3O3 538.2639 and 540.2618; found 538.2643 [M + H]+
3
4
CH2-), 3.46–3.37 (m, 6 H, CH2-NH), 2.35 (dt, JH,H = 6.9, JH,H and 540.2611 [M + H]+. * All the signals are broad due to intense
5126
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5115–5127

Self-Aggregation of 2-Substituted Benzene-1,3,5-Tricarboxamides
130, 606–611; c) T. F. A. De Greef, M. M. J. Smulders, M.
Wolffs, A. P. H. J. Schenning, R. P. Sijbesma, E. W. Meijer,
Chem. Rev. 2009, 109, 5687–5754; d) A. J. Markvoort,
H. M. M. ten Eikelder, P. A. J. Hilbers, T. F. A. de Greef, E. W.
Meijer, Nat. Commun. 2011, 2, 1517/1511–1517/1519.
[14] A. R. A. Palmans, J. A. J. M. Vekemans, E. E. Havinga, E. W.
Meijer, Angew. Chem. Int. Ed. Engl. 1997, 36, 2648–2651; An-
gew. Chem. 1997, 109, 2763.
[15] A. R. A. Palmans, J. A. J. M. Vekemans, H. Fischer, R. A.
Hikmet, E. W. Meijer, Chem. Eur. J. 1997, 3, 300–307.
[16] T.-Q. Nguyen, M. L. Bushey, L. E. Brus, C. Nuckolls, J. Am.
Chem. Soc. 2002, 124, 15051–15054.
[17] T.-Q. Nguyen, R. Martel, P. Avouris, M. L. Bushey, L. Brus,
C. Nuckolls, J. Am. Chem. Soc. 2004, 126, 5234–5242.
[18] a) L. Fielding, Tetrahedron 2000, 56, 6151–6170; b) R. S. Mac-
omber, J. Chem. Educ. 1992, 69, 375–378; c) P. Thordarson,
Chem. Soc. Rev. 2011, 40, 1305–1323.
[19] R. B. Martin, Chem. Rev. 1996, 96, 3043–3064.
[20] a) C. S. Johnson Jr., Prog. Nucl. Magn. Reson. Spectrosc. 1999,
34, 203–256; b) A. Macchioni, G. Ciancaleoni, C. Zuccaccia,
D. Zuccaccia, Chem. Soc. Rev. 2008, 37, 479–489; c) K. F. Mor-
ris, P. Stilbs, C. S. Johnson Jr, Anal. Chem. 1994, 66, 211–215.
[21] a) L. Allouche, A. Marquis, J.-M. Lehn, Chem. Eur. J. 2006,
12, 7520–7525; b) A. Perez, D. de Saa, A. Ballesteros, J. L. Ser-
rano, T. Sierra, P. Romero, Chem. Eur. J. 2013, 19, 10271–
10279.
association of the solute. ** Two aromatic signals (C-C=Oortho and
C-C=Opara) were not detected.
Crystallographic Information: CCDC-1055357 (for 9) contains the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Further details of the single-crystal X-ray diffraction study are pro-
vided in the Supporting Information.
Acknowledgments
The authors thank Dr. Armelle Vallat-Michel and Mr. Fredy Nyd-
egger (NPAC University of Neuchâtel) for her assistance with the
mass spectrometry and Dr. Sebastiano Guerra and Prof. De-
schenaux (UniNE) for POM and DSC analyses. Financial support
by the University of Neuchâtel and the Swiss National Science
Foundation (grant number 200020-140555) are gratefully acknowl-
edged.
[1] G. M. Whitesides, M. Boncheva, Proc. Natl. Acad. Sci. USA
2002, 99, 4769–4774.
[2] S. I. Stupp, L. C. Palmer, Chem. Mater. 2014, 26, 507–518.
[3] Y. Matsunaga, N. Miyajima, Y. Nakayasu, S. Sakai, M. Yonen-
aga, Bull. Chem. Soc. Jpn. 1988, 61, 207–210.
[4] a) P. Besenius, J. L. M. Heynens, R. Straathof, M. M. L.
Nieuwenhuizen, P. H. H. Bomans, E. Terreno, S. Aime, G. J.
Strijkers, K. Nicolay, E. W. Meijer, Contrast Media Mol. Im-
[22] a) I. B. Rietveld, D. Bedeaux, Macromolecules 2000, 33, 7912–
7917; b) A. Sagidullin, B. Fritzinger, U. Scheler, V. D. Skirda,
Polymer 2004, 45, 165–170.
[23] W. S. Price, F. Tsuchiya, Y. Arata, J. Am. Chem. Soc. 1999, 121,
11503–11512.
aging 2012, 7, 356–361; b) S. Cantekin, T. F. A. de Greef, [24] H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. Int.
A. R. A. Palmans, Chem. Soc. Rev. 2012, 41, 6125–6137; c) T.
Shikata, D. Ogata, K. Hanabusa, J. Phys. Chem. B 2004, 108,
508–514.
Ed. 2001, 40, 2004–2021; Angew. Chem. 2001, 113, 2056.
[25] G.-L. Law, T. A. Pham, J. Xu, K. N. Raymond, Angew. Chem.
Int. Ed. 2012, 51, 2371–2374.
[26] A. K. Chakraborti, L. Sharma, M. K. Nayak, J. Org. Chem.
2002, 67, 6406–6414.
[5] C. A. Hunter, J. K. M. Sanders, J. Am. Chem. Soc. 1990, 112,
5525–5534.
[6] L. Brunsveld, H. Zhang, M. Glasbeek, J. A. J. M. Vekemans,
E. W. Meijer, J. Am. Chem. Soc. 2000, 122, 6175–6182.
[7] a) M. P. Lightfoot, F. S. Mair, R. G. Pritchard, J. E. Warren,
Chem. Commun. 1999, 1945–1946; b) P. J. M. Stals, M. M. J.
Smulders, R. Martin-Rapun, A. R. A. Palmans, E. W. Meijer,
Chem. Eur. J. 2009, 15, 2071–2080.
[8] a) M. L. Bushey, A. Hwang, P. W. Stephens, C. Nuckolls, J.
Am. Chem. Soc. 2001, 123, 8157–8158; b) M. L. Bushey, T.-Q.
Nguyen, C. Nuckolls, J. Am. Chem. Soc. 2003, 125, 8264–8269;
c) M. L. Bushey, T.-Q. Nguyen, W. Zhang, D. Horoszewski, C.
Nuckolls, Angew. Chem. Int. Ed. 2004, 43, 5446–5453; Angew.
Chem. 2004, 116, 5562.
[27] a) D. Kanamori, A. Furukawa, T.-A. Okamura, H. Yamamoto,
N. Ueyama, Org. Biomol. Chem. 2005, 3, 1453–1459; b) D.
Kanamori, T.-a. Okamura, H. Yamamoto, S. Shimizu, Y. Tsuji-
moto, N. Ueyama, Bull. Chem. Soc. Jpn. 2004, 77, 2057–2064;
c) D. Kanamori, T.-a. Okamura, H. Yamamoto, N. Ueyama,
Angew. Chem. Int. Ed. 2005, 44, 969–972; Angew. Chem. 2005,
117, 991.
[28] K. Wallenfels, K. Friedrich, F. Witzler, Tetrahedron 1967, 23,
1353–1358.
[29] X. Hou, M. Schober, Q. Chu, Cryst. Growth Des. 2012, 12,
5159–5163.
[30] M. M. L. Nieuwenhuizen, T. F. A. de Greef, R. L. J.
van der Bruggen, J. M. J. Paulusse, W. P. J. Appel, M. M. J.
Smulders, R. P. Sijbesma, E. W. Meijer, Chem. Eur. J. 2010, 16,
1601–1612.
[9] a) D. Thevenet, Ph.D. thesis no. 2182, University of Neuchatel,
2010; http://doc.rero.ch/record/21252?ln=fr; b) D. Thevenet, R.
Neier, Synthesis 2011, 3801–3806.
[10] L. Schmidt-Mende, A. Fechtenkotter, K. Mullen, E. Moons,
R. H. Friend, J. D. MacKenzie, Science 2001, 293, 1119–1122.
[11] S. Kumar, Liq. Cryst. 2005, 32, 1089–1113.
[31] D. Wu, A. Chen, C. S. Johnson Jr., J. Magn. Reson., Ser. A
1995, 115, 260–264.
[32] OriginPro 8, Data Analysis and Graphing Software, OriginLab
Cooperation, Northhampton, MA 01060, USA.
[12] T. Curtius, J. Prakt. Chem. 1915, 91, 39–102.
[13] a) M. M. J. Smulders, M. M. L. Nieuwenhuizen, T. F. A. [33] Perkin–Elmer Spectrum™ 5, Infrared Spectroscopy Software
de Greef, P. van der Schoot, A. P. H. J. Schenning, E. W. Me-
ijer, Chem. Eur. J. 2010, 16, 362–367; b) M. M. J. Smulders,
A. P. H. J. Schenning, E. W. Meijer, J. Am. Chem. Soc. 2008,
Platform, Perkin–Elmer, Waltham, MA 02451, USA.
Received: April 21, 2015
Published Online: July 14, 2015
Eur. J. Org. Chem. 2015, 5115–5127
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5127