New bisamides gelators: Relationship between chemical structure and fiber morphology

Article abstract of DOI:10.1016/S0040-4039(03)00456-8

Different dialkoxybenzoic acid derivatives with identical alkyl chain lengths were synthesized and their properties as organogelators evaluated. Only the compounds bearing amide groups behave like gelators. Their gelation abilities and phase diagrams were described. A structural study was conducted by freeze-fracture electron microscopy and showed that the methyl ester formed platelet-like aggregates whereas the corresponding free acid formed thin fibers in the gel.

Full text of DOI:10.1016/S0040-4039(03)00456-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3171–3174
New bisamides gelators: relationship between chemical structure
and fiber morphology
Rolf Schmidt, Fahuzi B. Adam, Marc Michel, Marc Schmutz, Gero Decher and Philippe J. Me´sini*
Chemistry of Associating Systems, Institut Charles Sadron, 6 rue Boussingault, 67083 Strasbourg Cedex, France
Received 12 February 2003; revised 17 February 2003; accepted 17 February 2003
Abstract—Different dialkoxybenzoic acid derivatives with identical alkyl chain lengths were synthesized and their properties as
organogelators evaluated. Only the compounds bearing amide groups behave like gelators. Their gelation abilities and phase
diagrams were described. A structural study was conducted by freeze-fracture electron microscopy and showed that the methyl
ester formed platelet-like aggregates whereas the corresponding free acid formed thin fibers in the gel. © 2003 Elsevier Science
Ltd. All rights reserved.
Organogelators1 are a growing class of low molecular
mass molecules that possess the ability to gel solvents at
low concentrations (typically a few weight percent). The
origin of this behavior is their ability to spontaneously
self-assemble into fibrillar aggregate networks that
entrap the solvent molecules. As a result, interesting
viscoelastic properties can be observed such as a dra-
matic increase in viscosity (4 to 5 orders of magnitude
with respect to the pure solvent), which often leads to
the formation of self-supported gels. These materials
are widely used as rheomodifying additives, for instance
in lubricating greases2 and gelled fuels.3 New potential
applications in pharmacology,4 oil-spill recovery5 or as
mesoporous materials6 are currently under investiga-
tion. It is often very hard to predict the gelation
properties of a molecule from the chemical structure
alone. Structure–activity relationship studies on this
type of molecule are required in order to appropriately
modify existing gelators or to prepare new ones.
in this series (Scheme 2) and present their characteristic
gelation behavior. A structural study was conducted by
freeze-fracture electron microscopy.
Scheme 1. Chemical structure of 1n, organogelators for n]3.
We recently reported that the oligoamides 1n (Scheme
1) are organogelators of aromatic solvents such as
toluene or xylene for n]3.7 Electron microscopy, along
with small-angle scattering experiments enabled us to
visualize and characterize the gels at a nanometric
scale.8 We prepared shorter analogs of these
oligoamides in order to investigate the influence of the
different structural elements on their gelation proper-
ties. Herein, we report the synthesis of the first analogs
Keywords: gels; organogelators; bisamides; electron microscopy.
* Corresponding author. Tel.: +33-(0)388-414-070; fax: +33-(0)388-
414-099; e-mail: mesini@ics.u-strasbg.fr
Scheme 2. Synthesized analogs.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00456-8

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R. Schmidt et al. / Tetrahedron Letters 44 (2003) 3171–3174
Scheme 3. Reagents and conditions: (a) EDCI (3 equiv.), C10H21NH2 (1 equiv.), HOBt (0.16 equiv.), NMP, 92%; (b) 4 M HCl in
EtOAc; (c) C10H21COOH (1 equiv.), EDCI (2 equiv.), 72%.
All the synthesized analogs contain the dialkoxybenzoic
core structure from 1n and the length of the alkyl chains
is identical in all cases. Compounds 2a, 2b and 3
possess two amide groups, like the trimer 13, which is
the shortest gelator in the original series.7 Compounds
2a and 2b are symmetrical with respect to the amide
group, i.e. the amides are in a parallel orientation. In
compound 3, the orientation of the amides is antiparal-
lel. As a control, we also studied 4, which possesses no
amide groups. Synthesis of the bisamide 2a was
achieved by bis-alkylation of 3,5-dihydroxybenzoic acid
methyl ester with 11-bromo-N-decylundecanamide. The
reaction was carried out under phase transfer catalysis
conditions with excess K2CO3 and gave 2a9 in 58%
yield. Compound 4 was prepared under the same condi-
tions using 1-bromodocosane as alkylating agent.10
Hydrolysis of 2a (Scheme 2) by LiOH in MeOH gave
2b.11 Coupling of acid 512 and decylamine with EDCI
as a condensing agent provided amide 6 in good yield
(92%) (Scheme 3). Treatment of 6 with a 4 M HCl
solution in EtOAc led to the cleavage of the BOC
protecting group. The resulting ammonium salt was not
purified but immediately coupled with undecanoic acid
in the presence of EDCI to provide the final amide 313
(72%).
studied. Only 3 displays higher gel concentrations and
lower transition temperatures than the other gelators.
This can partly be explained by the difference in melt-
ing points of the pure compounds (2a: 104°C, 3: 90°C):
according to the Schro¨der–van Laar relation,16 the gel-
to-sol transition temperature is related to the melting
temperature of the pure gelator.
The internal gel structures were investigated by freeze-
fracture electron microscopy (Fig. 2), according to the
procedure described previously.7 The gels obtained
from 2a and 3 (Figs. 2a and 2b) exhibit similar struc-
tures in the gel: platelet-like aggregates with varying
width (150–180 nm) and length (up to several mm)
throughout the sample. Slight structural differences can
be observed between 2a and 3: inside the 2a platelets,
smaller fibrils can be distinguished (Fig. 2a, arrow). The
structures from gels of 3 show no individual fibrils, but
Table 1. Gelation test for 3% by weight of 1–4 in various
solvents
Solvent
13–14
2a
2b
3
4
CHCl3
Hexane
MeOH
Benzene
Toluene
p-Xylene
S
I
C
G
G
G
S
I
C
G
G
G
S
I
C
G
G
G
S
I
C
G
G
G
S
I
C
S
S
S
The gelling abilities of the synthesized molecules were
tested with different solvents at a concentration of 3%
by weight (Table 1). The samples were heated in sealed
vials until dissolution of the solid was complete. The
isotropic solutions were then cooled back to room
temperature. Depending on the solvent and the sub-
strate, different cases were observed upon cooling: a gel
formed (G), the compound was soluble (S) or the
compound crystallized (C). In some cases, the com-
pounds were not soluble, even in boiling solvent (I).
Compounds 2a, 2b and 3 were able to gel the same
solvents as the parent gelator 13, i.e. benzene and
toluene. Compound 4 showed no gelation properties
under the same conditions. Thus, the presence of amide
groups in the molecule is crucial for the gelation pro-
cess. This result is not as obvious as it may seem as
many organogelators without any polar groups or H-
donor or acceptor groups at all have been described.
This is especially true for the di-n-alkoxybenzenes
described by Pozzo et al.,14 that have a chemical struc-
ture very similar to 4 but with shorter alkyl chains.
S, soluble; C, recrystallizes; I, insoluble; G, gel (see text).
The phase diagrams were established for different gela-
tors in toluene (Fig. 1). We used the dropping ball
technique15 to measure the gel-to-sol transition temper-
atures. The minimal gel concentrations and the stability
of the gels are comparable for all of the compounds
Figure 1. Gel-to-sol transition temperatures in toluene: ꢀ, 13;
ꢁ, 2a; ꢂ, 2b; 2, 3.

R. Schmidt et al. / Tetrahedron Letters 44 (2003) 3171–3174
3173
plays a key role in the aggregation process: the presence
of the acid group prevents the lateral packing of fibrils
into larger objects as for 2a and limits agreggation to
one dimensional fibers. This is another example of the
fact that a small change in the chemical structure can
lead to drastically different internal gel structures.1
While the parallel/antiparallel orientation of the amide
groups in the alkyl chains leads to minor differences of
the internal gel structure, we identified the functional
group on the aromatic ring to be the most important
factor that governs aggregation extent and directional-
ity of the gel-constituting aggregates. The synthesis and
evaluation of extended ester analogues is under
investigation.
Acknowledgements
This work was supported by a MESR fellowship (R.S.).
Dr. P. Schultz is deeply thanked for the use of the
cryofracturing apparatus developed by Dr. J.-C. Homo
at the IGBMC UMR 7104, Illkirch, France
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9. Mp 102–104°C; 1H NMR (200 MHz, CDCl3): l (ppm)
7.14 (m, 2H, C2-H, C6-H), 6.62 (t, 1H, J=2.2 Hz,
C4-H), 5.48 (wide s, 2H, NH), 3.95 (t, 4H, J=6.5 Hz,
ArOCH2), 3.88 (s, 3H, COOCH3), 3.22 (q, 4H, J=6.5

3174
R. Schmidt et al. / Tetrahedron Letters 44 (2003) 3171–3174
Hz, CH2NHCO), 2.14 (t, 4H, J=7.5 Hz, CH2CONH),
ArOCH2), 3.88 (s, 3H, COOCH3), 3.21 (q, 4H, J=6.6
Hz, CH2NHCO), 2.13 (t, 4H, J=7.6 Hz, CH2CONH),
1.75 (p, 4H, J=6.7 Hz, ArOCH2CH2), 1.60 (p, 4H,
J=6.9 Hz, CH2CH2CONH), 1.43 (p, 4H, J=6.7 Hz,
CH2CH2NHCO), 1.28–1.24 (m, 52H), 0.86 (t, 6H, J=6.4
Hz, CH3); 13C NMR (50 MHz, CDCl3): l (ppm) 173.0,
167.0, 160.1, 131.8, 107.6, 106.5, 68.3, 52.1, 39.5, 36.9,
31.9, 29.7, 29.5, 29.3, 26.9, 25.9, 25.8, 22.6, 14.1; IR
(KBr) wmax 3305, 2925, 2855, 1730, 1639, 1546, 1458,
1326, 1239, 1168, 1121 cm−1; Mass (FAB+) calcd for
C50H90N2O6: 814.7; found: m/z 815.7 (MH+). Anal. calcd
for C50H90N2O6: C, 73.66; H, 11.13; N, 3.44. Found: C,
73.45; H, 10.92; N, 3.40.
1.75 (p, 4H, J=6.5 Hz, ArOCH2CH2), 1.60 (p, 4H,
J=6.6 Hz, CH2CH2CONH), 1.28 (m, 56H), 0.86 (t, 6H,
J=6.7 Hz, CH3); 13C (50 MHz, CDCl3): l (ppm) 173.0,
167.0, 160.1, 131.8, 107.6, 106.6, 68.3, 52.1, 39.5, 36.9,
31.9, 29.3, 26.9, 22.6, 14.1; IR (KBr) wmax 3312, 2919,
2851, 1708, 1636, 1536, 1469, 1434, 1357, 1302, 1239
cm−1
C50H90N2O6: 815.6877).
. HRMS (FAB+) 815.6978 (M−H+, calcd for
1
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7.16 (dd, 2H, J=6 Hz, J=2 Hz, C2-H, C6-H), 6.63 (t,
1H, J=2 Hz, C4-H), 3.95 (t, 4H, J=6.3 Hz, ArOCH2),
3.90 (s, 3H, COOCH3), 1.78 (m, 4H, ArOCH2CH2),
1.56–1.20 (m, 76 H), 0.86 (t, 6H, J=6.4 Hz, CH3); 13C
NMR (50 MHz, CDCl3): l (ppm) 171.1, 160.2, 130.8,
106.5, 68.3, 32.1, 29.6, 29.5, 29.3, 27.1, 15.3; IR (KBr)
wmax 2921, 2925, 2853, 1725, 1602, 1472, 1444, 1322, 1237,
1167 cm−1. Anal. calcd for C52H96O4: C, 79.53; H, 12.32;
O, 8.15. Found: C, 79.37; H, 12.19; O, 8.13.
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1
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J=2.2 Hz, C4-H), 5.62 (s large, 2H, NH), 3.93 (t, 4H,
J=6.5 Hz, ArOCH2), 3.24 (q, 4H, J=6.4 Hz,
CH2NHCO), 2.19 (t, 4H, J=7.3 Hz, CH2CONH), 1.75–
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106.3, 70.9, 43.1, 36.7, 31.8, 29.2, 26.8, 25.8, 23.1, 15.2;
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1305 cm−1. Anal. calcd for C49H88N2O6: C, 73.45; H,
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C4-H), 5.56 (s large, 2H, NH), 3.94 (t, 4H, J=6.5 Hz,