Benzyl and tert-butyl carbamate derivatives of 1,ω-amino acids as simple yet efficient gelators

Article abstract of DOI:10.1016/j.tet.2007.03.126

We report the synthesis and a study of the gelation properties of a series of N-protected long-chain amino acids. Especially, benzyl and tert-butyl carbamate derivatives of 11-aminoundecanoic acid in their deprotonated form can gelate polar organic solvents and water at very low concentration (less than 5 mM). This is explained by the contribution of multiple forces-H-bond, van der Waals and ionic interactions-in the gel aggregate formation and stabilization, which is confirmed by the experimental data. Among the series of compounds investigated, only a dimer of 11-aminoundecanoic acid is capable of gelating toluene, which stems from the increased number of hydrogen bonding sites in the main aliphatic chain.

Full text of DOI:10.1016/j.tet.2007.03.126

Tetrahedron 63 (2007) 7482–7488
Benzyl and tert-butyl carbamate derivatives of 1,u-amino
acids as simple yet efficient gelators
a
Anthony D’Aleo, Jean-Luc Pozzo, Karine Heuze, Fritz Vogtle and Frederic Fages
a
b
c,
ꢀ a
€
ꢀ ꢀ
*
ꢀ
a
´
LCOO UMR 5802 CNRS, Universite Bordeaux 1, 33405 Talence Cedex, France
Kekule-Institut fu€r Organische Chemie und Biochemie, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
b
´
GCOM2 UMR 6114 CNRS, Universite de la Mediterranee, Faculte des Sciences de Luminy, Case 901,
c
´
13288 Marseille Cedex 9, France
´
´
´
Received 3 November 2006; revised 2 March 2007; accepted 16 March 2007
Available online 24 March 2007
Abstract—We report the synthesis and a study of the gelation properties of a series of N-protected long-chain amino acids. Especially, benzyl
and tert-butyl carbamate derivatives of 11-aminoundecanoic acid in their deprotonated form can gelate polar organic solvents and water at
very low concentration (less than 5 mM). This is explained by the contribution of multiple forces—H-bond, van der Waals and ionic inter-
actions—in the gel aggregate formation and stabilization, which is confirmed by the experimental data. Among the series of compounds
investigated, only a dimer of 11-aminoundecanoic acid is capable of gelating toluene, which stems from the increased number of hydrogen
bonding sites in the main aliphatic chain.
Ó 2007 Published by Elsevier Ltd.
1. Introduction
the gel materials with specific supramolecular functions,
such as molecular recognition, photo- or electroactivity.1,2
However, as they are usually available in small amounts be-
cause their synthesis needs numerous synthetic steps, they
are not often suited for large-scale applications. Structurally
simple compounds, that can be obtained in gram scale quan-
tities from cheap precursors in a limited number of synthetic
steps, are also of great interest because they allow the pro-
duction of nanostructured materials with thermoreversible
properties at very moderate costs.1b,3 Such systems can
find applications as host matrices or media for a variety of
applications, including sensing and separation technologies,
catalysis, (bio)mineralization, etc.
Molecular gels represent outstanding functional nanoscale
materials with high potential in a wide range of advanced
applications.1 Their formation stems from the spontaneous
but controlled self-assembly of low molecular mass com-
pounds into fibrous architectures, which, in turn, form
entangled three-dimensional networks entrapping solvent
molecules.1a,g In contrast to the case of their polymeric
counterparts, molecular gels involve discrete molecular
components with well-defined chemical structures. It is
therefore possible, by introducing subtle changes in the
chemical composition of the gelator backbone, to fine-tune
the morphology, chirality and size of the aggregates and,
ultimately, the macroscopic properties of the gel.1 Arguably
this unique feature largely contributes to motivate the great
deal of activity towards the synthesis of new gelator mole-
cules. When considering the data available in the literature
over the last 20 years, it is amazing to realize that both kinds
of molecular systems, structurally sophisticated chemical
entities and, on the other hand, simple compounds, can be
found in the library of gelators. The former are generally
multi-component molecular systems and they are appealing
in that they give the opportunity to endow the aggregates and
Recently, we reported in a preliminary communication the
gelling behaviour of a series of N-acyl-1,u-amino acid
derivatives.4 Within the series, amide compounds including
the 11-aminoundecanoic acid (AUDA) motif were proven
very effective and versatile gelators of water and/or organic
solvents.5,6 In this paper, we focus on a series of structurally
simple carbamate derivatives of 1,u-amino acids such as
CBZ-n-R with different chain lengths (n¼3, 5, 7, 10, 11,
12) and Boc-10-R (Scheme 1). The effects of the ionization
state of the terminal carboxylic acid functionality (R¼H or
M+), and of the nature of the alkali metal cation (M¼Li,
Na, K, Rb, Cs for n¼10) are described. In line with our
investigation on AUDA-based compounds,5 the synthesis
and gelation abilities of a new dimeric species of CBZ-10-
H, CBZ-10-10-H, are also reported (Scheme 1).
Keywords: Self-assembly; Molecular gels; Amino acids; Hydrogen bond-
ing; Ionic interactions.
* Corresponding author. Fax: +33 (0)4 91 82 95 81; e-mail: fages@luminy.
univ-mrs.fr
0040–4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.03.126

A. D’Aleꢀo et al. / Tetrahedron 63 (2007) 7482–7488
7483
O
O
O
O
O
N
H
(CH2)n
O
N
H
OR
OR
R = H, Na
BOC-10-R
CBZ-n-R (n = 3, 5, 7, 10, 11, 12)
O
O
O
O
O
HOSu, DCC
DMF
O
N
H
N
O
N
H
OH
O
11-AUDA
O
O
O
O
N
H
N
H
OH
CBZ-10-10-H
Scheme 1. Synthesis of the gelators.
2. Results and discussion
insoluble in solvents of low polarity. Remarkably, these
systems are also efficient gelators of concentrated aqueous
NaOH (pH¼14), which indicates an ambidextrous behav-
iour.3b The need for such a high pH value for self-
aggregation to be observed has already been reported for
fatty acids.8 None of these compounds in their neutral
carboxylic form are gelators in the solvents investigated. In-
stead, the protonated acids are highly soluble in the polar
solvents. The only compound, which is able to gelate tolu-
ene, is the dimer CBZ-10-10-H as a result of a large number
of hydrogen bonding sites, consistent with a trend previously
reported for AUDA-containing amide derivatives.5 At room
temperature, the minimum gelation concentration (MGC)
was about 7 mM in toluene, which is remarkably low, and
the gel-to-solution phase transition temperature, Tgel, was
observed to reach 82 ꢀC at 20 mM. Within the series of
compounds, CBZ-10-Na was found to gelate DMF at a con-
centration of ca. 5ꢁ10ꢂ3 M at room temperature, which
represents less than 0.2 wt %, indicating that this substance
has the character of a ‘supergelator’.9 The gels of CBZ-
10-Na at such low concentration in DMF were transparent
and thermoreversible over a period of more than 10 months.
Transmission electron microscopy of a DMSO gel of CBZ-
10-Na provided direct evidence of an entanglement of
numerous, randomly orientated thin filaments, the diameter
of the smallest ones being approximately 30 nm (Fig. 1).
Rheology confirmed the occurrence of a rigid three-
dimensional network in the gel samples. A DMF gel of
CBZ-10-Na (20 mM) was subjected to a nondestructive
2.1. Synthesis
Compounds CBZ-n-H and Boc-10-H were obtained in good
yields according to well-known synthetic procedures widely
used for the protection of amino groups in oligopeptide
synthesis (Scheme 1).7 Especially, excellent gelators can
be produced in large amounts from the commercially avail-
able and not expensive AUDA starting material, which is
used industrially to produce Nylon-11Ò. The dimer species,
CBZ-10-10-H, was prepared by a two-step procedure from
CBZ-10-H. The latter was activated via DCC-mediated
condensation with N-hydroxysuccinimide to give the corre-
sponding ester CBZ-10-OSu. The latter was reacted with
AUDA in DMF to afford the dimer. The sodium salt
and, in the case of CBZ-10-H, the alkali metal salts of the
N-protected-amino acid compounds were obtained upon
treatment of the acid with 1 molar equiv of the correspond-
ing metal hydroxide in solution.
2.2. Gelation experiments
The gelation ability of the compounds investigated was
tested for 10 different solvents with 20 mM as a standard
concentration. The results are summarized in Table 1.
Only the sodium salts of the N-protected AUDA compounds,
CBZ-n-R and Boc-10-R (R¼H, Na), appeared to be gelators
of polar organic solvents (DMF, DMSO) while they are
Table 1. Gelation ability of the gelators investigated in this study
R¼
CBZ-5-R
CBZ-7-R
CBZ-10-R
CBZ-11-R
CBZ-12-R
Boc-10-R
CBZ-10-10-R
H
Na
H
Na
H
Na
H
Na
H
Na
H
Na
H
Na
Toluene
EtOAc
THF
Dioxane
MeOH
DMF
DMSO
Propylene carbonate
N,N-Dimethylacetamide
H2O (pH¼14)
I
I
I
P
P
P
P
P
P
P
S
S
S
S
S
I
I
P
P
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
S
S
S
S
P
S
S
S
S
G
I
I
I
I
P
S
G
G
G (7)
P
P
P
I
P
S
VS
P
P
I
I
I
I
P
P
P
P
P
P
P
P
I
P
S
S
S
S
S
P
P
P
S
S
S
S
G
P
P
P
S
S
S
S
G
P
P
P
S
S
S
S
G
P
G (17)
G
VS
P
P
G (15)
G
G
G
G
I
I
I
G (4)
G
G
G
G (5)
G (8)
G
G
G
G
G (4)
G
G
G
G
P
G (5)
S
Gelator concentration 20 mM (room temperature). G, gel; S, solution; VS, viscous solution; P, precipitate; I, insoluble when heated. Values in parentheses are
MGC at 25 ꢀC.

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A. D’Aleꢀo et al. / Tetrahedron 63 (2007) 7482–7488
0 ꢀC. A similar trend has been observed for isophthalic
acid derivatives forming long organic fibres.11 Similarly,
replacement of sodium ions by ammonium cations (NH+4,
n-Bu4N+) led to the loss of gelation. When KryptofixÒ
[211] (a selective Na+ binder) was introduced into a hot
solution of CBZ-10-Na, gelation failed again, which points
to the intimate participation of the sodium cation in the
self-assembly and stabilization of the gel aggregate.
2.3.2. Hydrogen bond formation. The FTIR spectrum of
a xerogel of CBZ-10-Na prepared from a DMF gel is char-
acterized by bands attributed to hydrogen bonding and is
similar to that of the solid obtained from evaporation of
a methanol solution, which indicates the marked propensity
of the compound to form hydrogen bonds. Bands at
3360 cmꢂ1 and 1690 cmꢂ1 were observed for N–H and
1
Figure 1. TEM image of xerogel prepared from a DMSO gel of CBZ-10-Na
(4 mg/mL) (scale bar 100 nm).
C]O stretching vibrations, respectively. H NMR spectra
of CBZ-10-Na in DMSO-d6 (12 mM) were recorded at
different temperatures. At 25 ꢀC, the spectrum of the gel
showed resonance patterns close to those recorded for a
methanol-d4 solution. However, the signals of the gelator
molecules in the gel network were observed to be shifted
and considerably broadened. As compared to the solvent
signal intensity, the peaks also displayed very low intensity
in the gel state relative to the solution. Such features were al-
ready reported for other self-assembled gels and are typical
of molecular systems with long correlation times as a result
of aggregation.12 When the temperature was increased, the
ratio of the solvent signal (nondeuterated residue of
DMSO-d6) intensity to the urethane NH signal intensity sig-
nificantly increased (Fig. 3a), which is consistent with the
dissociation of the gel network leading to an increased gela-
tor concentration in the solution. The plot in Figure 3 shows
a gradual disassembly, which is complete by 50 ꢀC, which is
in agreement with the value of 48 ꢀC for Tgel determined by
the tube inversion method. Monitoring of the gelator’s chem-
ical shift changes as a function of temperature confirmed the
occurrence of hydrogen bond formation (Fig. 3b). As the
temperature increased, the NH proton of the urethane frag-
ment was shifted upfield (Dd¼0.26 ppm), while the phenyl
and benzylic methylene protons were only very slightly
shifted downfield (Dd<0.02 ppm).
frequency sweep experiment with a constant shear stress of
20 Pa at room temperature and the result is given in Figure 2.
This shows that the G0 and G00 parameters are independent of
oscillation frequency over three decades and take the values
10,000 Pa and 1000 Pa, respectively, at 1 Hz. G0 is thus
one order of magnitude larger than G00, which reflects the
dominant elastic character of this gel.10
2.3. Factors influencing the gelation ability
2.3.1. Influence of the counterion. From the data in Table 1,
the presence of an ionized carboxylate function is required
for gelation to be observed. The neutral form CBZ-10-H
and a fortiori the ethyl ester derivative CBZ-10-Et did not
show any gelation ability and only gave rise to solutions in
DMF even at high concentration. To confirm the occurrence
of an ionic interaction contributing to self-assembly, com-
pound CBZ-10-R was investigated in which the nature of the
alkali metal cation was varied (R¼Li, Na, K, Rb). Indeed
the gelation ability was found to be sensitive to the nature
of the metal. Gels could be prepared with Na+ and Rb+ but
not with Li+ and K+. In the case of Rb+, a very weak gel at
high concentration (70 mM) could only be observed at
2.3.3. Influence of the (CH2)n spacer. As mentioned in
Table 1, the MGC in DMF decreases with the length of the
(CH2)n spacer. The MGC values are around 15 mM for
n¼5, 7, and below 10 mM for n¼10, 11, 12. The commer-
cially available CBZ-3-Na was also able to gelate DMF,
but only at high concentration (70 mM) and the gel was
opaque and weak. This trend is due to the occurrence of sol-
vophobic interactions during the gelation process; the longer
the chain the larger the inter-chain interactions via van der
Waals interactions. Such behaviour is well-known for self-
assembling systems containing long alkyl chains.13 It should
be mentioned that the MGC value determined for CBZ-11-
Na was found to be lower than that of CBZ-10-Na and
CBZ-12-Na. In order to clarify this result, the Tgel values
were plotted as a function of gelator concentration in DMF
(Fig. 4). These curves clearly indicate that the melting tem-
perature of the gels increases with concentration and tends to
level off at higher concentrations. Noticeably, compounds
with n¼10 and 12 show a very similar behaviour, forming
highly thermally stable gels (Tgel ca. 100 ꢀC) above
105
105
G´ (Pa)
G˝(Pa)
104
104
1000
100
1000
100
0.01
0.1
1
10
(Hz)
Figure 2. Frequency sweep experiments on a DMF gel of CBZ-10-Na
(20 mM, 25 ꢀC). Three different measurements of G0 and G00 as a function
of oscillation frequency (the gel was heated to yield the sol and reformed
upon cooling between each measurements). The applied shear stress is
20 Pa and the experiment is performed in the linear regime.

A. D’Aleꢀo et al. / Tetrahedron 63 (2007) 7482–7488
7485
(a)
chains.13 It is considered to be indicative of the presence
of the molecules in the gel aggregate in their extended
‘zig-zag’ conformation, which controls the extent of
H-bond and ionic interactions at the termini and, in turn,
aggregate stability. All together, the results support a model
of one-dimensional aggregation as sketched in Scheme 2,
which is consistent with the literature data on fatty acids.4,13
30
25
20
15
10
5
ionic
H-bonds
interactions
O
O
0
-
O
N
H
O
20
30
40 50
Temperature (°C)
60
70
Na+
(b)
O
O
7.5
7
-
O
N
H
O
Na+
O
O
-
O
N
H
O
6.5
6
Na+
van der Waals
interactions
Phenyl
NH
5.5
5
Benzylic
Scheme 2. One-dimensional aggregate model of CBZ-n-Na in the gel
phase.
2.3.4. CBZ versus Boc. The gelation properties of CBZ-10-
Na and Boc-10-Na were compared in H2O at pH¼14. Both
compounds have a MGC of about 5 mM (0.15 wt %) at
25 ꢀC, which makes them also supergelators of water at
highly basic pH. The gel-to-sol phase transition temperature
was plotted against concentration (Fig. 5). The results show
a higher thermal stability for the CBZ N-protected com-
pound relative to the Boc derivative. Remarkably, the Tgel
value for CBZ-10-Na at 25 mM is high (95 ꢀC) and close
to the boiling point of water, which reflects the remarkable
stability of the self-assemblies in water. It is also worth
20
30
40 50
Temperature (°C)
60
70
Figure 3. 1H NMR experiments on a DMSO-d6 gel of CBZ-10-Na
(12 mM). (a) Changes of the solvent to gelator signal (N–H) intensity ratios
(Isol/Igelator) and (b) changes of selected gelator chemical shifts (d) versus
temperature.
50 mM. Interestingly, the curve obtained for n¼11 is below
those of the two former compounds. This odd/even effect has
already been observed for gelators containing long alkyl
100
a)
90
b)
100
90
80
70
60
50
40
30
20
10
0
c)
80
70
60
50
40
30
20
10
0
10
20
30
Concentration (mM)
40
50
60
0
10
20
Concentration (mM)
30
40
Figure 4. Plots of Tgel against gelator concentration in DMF: (a) CBZ-10-
Na, (b) CBZ-12-Na, (c) CBZ-11-Na.
Figure 5. Plots of Tgel against gelator concentration in H20 at pH¼14: CBZ-
10-Na (filled symbols), Boc-10-Na (empty symbols).

7486
A. D’Aleꢀo et al. / Tetrahedron 63 (2007) 7482–7488
mentioning that gelation was complete in ca. 1 h with Boc-
10-Na at 10 mM while the gelation time was only a few
minutes with CBZ-10-Na. The discrepancy in thermal and
kinetic features could arise from the occurrence of p-stack-
ing interactions and a lower steric demand for the CBZ
derivative as compared to the bulky tert-butyl-containing
compound. Intriguingly, however, rheological experiments
pointed to a higher mechanical rigidity of the Boc-10-Na
network (30 mM). This system has G0 and G00 parameters
that are independent of the oscillation frequency, and the
values obtained at 1 Hz are 1,70,000 Pa and 1200 Pa, respec-
tively. Thesevalues are typical for a solid-like gel with a clear
viscoelastic behaviour. Under the same conditions, the DMF
gel of CBZ-10-Na has G0 and G00 values of 19,000 Pa and
1200 Pa, respectively. Therefore, it is the best gelator with
regard to gelation time and thermal stability but has lower
rigidity. The origin of this disparity has not been the subject
of further investigation and remains unclear at this point. In
the literature, such behaviour has already been observed and
kinetic effects have been proposed.14
4.2. Syntheses
4.2.1. General procedure for the synthesis of compounds
CBZ-n-H (n=5, 7, 9, 10, 11, 12). Benzyloxycarbonyl chlo-
ride (11 mmol) was added dropwise to a solution of the
corresponding 1,u-amino acid (10 mmol) in aqueous
NaOH (11 mmol) at 0 ꢀC. The resulting suspension was
stirred for 1 h. Concentrated HCl was then added under
vigorous stirring until pH 2. The precipitated solid was fil-
tered off and recrystallized twice from methanol. The
desired products were obtained in good yields (75–
85%). The sodium salts were obtained upon mixing the
corresponding acid with the stoichiometric amount of
NaOH in 1/1 (v/v) H2O/MeOH and evaporation of the
mixture to dryness. All compounds were obtained as
white solids.
4.2.1.1. CBZ-5-H. FTIR (KBr) 3361, 2926, 2851, 1690,
1633, 1528 cmꢂ1; H NMR ((CD3)2SO/CD3OD, 2/1, v/v)
1
d 7.40–7.20 (m, 5H), 5.03 (s, 2H), 3.05 (t, J¼6.8 Hz, 2H),
2.15 (t, J¼7 Hz, 2H), 1.30–1.20 (m, 6H). Elemental analysis
calcd (%) for C14H19NO4 (265): C 63.38, H 7.22, N 5.28;
found: C 62.93, H 7.26, N 5.24.
3. Conclusion
The present study has demonstrated that very simple yet
efficient gelators can be produced in large amounts from
1,u-amino acids and classical reagents that form carbamate
amino-protecting group. Especially, the compounds contain-
ing 10 methylene groups display remarkable gelation ability
in polar solvents and also in highly basic water, acting as
‘supergelators’. The results clearly indicate the contribution
of multiple forces—H-bond, van der Waals and ionic inter-
actions—in the gel aggregate formation and stabilization,
which confirms the model of one-dimensional aggregation
proposed previously (Scheme 2).4 Gelation of nonpolar sol-
vents, such as toluene, is possible by increasing the number
of hydrogen bonding sites in the main aliphatic chain, as
illustrated by the dimer compound CBZ-10-10-H. All to-
gether, the data allow us to delineate the influence of critical
structural parameters and provide useful guidelines for pro-
ducing gel materials with tailored characteristics. Moreover,
the fact that some of the compounds are able to gelate highly
concentrated alkaline solutions may be interesting for appli-
cations.
4.2.1.2. CBZ-5-Na. FTIR (KBr) 3362, 2926, 2854,
1691, 1560, 1529 cmꢂ1
.
4.2.1.3. CBZ-7-H. FTIR (KBr) 3363, 2922, 2852, 1690,
1
1634, 1528 cmꢂ1; H NMR ((CD3)2SO/CD3OD, 2/1, v/v)
d 7.35–7.25 (m, 5H), 5.02 (s, 2H), 3.08 (t, J¼6.8 Hz, 2H),
2.15 (t, J¼6.9 Hz, 2H), 1.30–1.20 (m, 10H). Elemental anal-
ysis calcd (%) for C16H23NO4 (293): C 65.51, H 7.90, N
4.77; found: C 65.13, H 7.86, N 5.04.
4.2.1.4. CBZ-7-Na. FTIR (KBr) 3359, 2922, 2861,
1688, 1560, 1530 cmꢂ1
.
4.2.1.5. CBZ-10-H. FTIR (KBr) 3363, 2926, 2851,
1690, 1635, 1528 cmꢂ1; 1H NMR ((CD3)2SO/CD3OD, 2/1,
v/v) d 7.38–7.25 (m, 5H), 5.14 (s, 2H), 3.04 (t, J¼6.7 Hz,
2H), 2.15 (t, J¼7.2 Hz, 2H), 1.35 (m, 16H); 13C NMR
d 177.25, 158.2, 138.7, 129.5, 128.9, 128.8, 67.1, 35.2,
31.1, 30.7, 30.55, 30.4, 29.9, 29.3, 27.9, 26.1. Elemental
analysis calcd (%) for C19H29NO4 (335): C 68.03, H 8.71,
N 4.18; found: C 68.43, H 9.03, N 4.24.
4. Experimental
4.1. General
4.2.1.6. CBZ-10-Na. FTIR (KBr) 3362, 2926, 2854,
1690, 1560, 1529 cmꢂ1
.
Chemicals were purchased from Aldrich and Merck, and
were used as supplied. N-Carbobenzoxy-4-aminobutyric
acid (CBZ-3-H) was obtained from TCI. The 12-membered
amino acid was synthesized according to a published pro-
cedure.15 1H and 13C NMR spectroscopies were performed
using a Bruker AM 400 apparatus operating at 400 MHz
and 100.6 MHz, respectively. NMR spectra were obtained
at 25 ꢀC unless otherwise stated. Gelation tests and Tgel
determinations were performed using the inverted-test tube
method as published elsewhere.16 Transmission electron
microscopy was performed with a JEOL 2000 apparatus.
The gels were deposited on copper grids coated with a carbon
film and evaporated under vacuum. The rheological setup
was described in a previous publication.17
4.2.1.7. CBZ-11-H. FTIR (KBr) 3361, 2927, 2854,
1690, 1635, 1527 cmꢂ1; 1H NMR ((CD3)2SO/CD3OD, 2/1,
v/v) d 7.36–7.25 (m, 5H), 4.95 (s, 2H), 3.04 (t, J¼6.9 Hz,
2H), 2.15 (t, J¼7.2 Hz, 2H), 1.35 (m, 18H). Elemental
analysis calcd (%) for C20H31NO4 (349): C 68.74, H 8.94,
N 4.01; found: C 68.33, H 9.03, N 3.92.
4.2.1.8. CBZ-11-Na. FTIR (KBr) 3361, 2923, 2851,
1690, 1561, 1522 cmꢂ1
.
4.2.1.9. CBZ-12-H. FTIR (KBr) 3362, 2927, 2854,
1690, 1634, 1529 cmꢂ1; 1H NMR ((CD3)2SO/CD3OD, 2/1,
v/v) d 7.50–7.35 (m, 5H), 5.05 (s, 2H), 3.14 (t, J¼7.6 Hz,
2H), 2.15 (t, J¼7.5 Hz, 2H), 1.10–1.50 (m, 20H). Elemental

A. D’Aleꢀo et al. / Tetrahedron 63 (2007) 7482–7488
7487
analysis calcd (%) for C21H33NO4 (363): C 69.39, H 9.15, N
3.85; found: C 69.03, H 9.13, N 4.04.
off, washed several times with pentane and dried under
vacuum for 24 h. The compound was obtained as a white
solid in 34.5% yield (2.74 g). FTIR (KBr) 3312, 3036,
4.2.1.10. CBZ-12-Na. FTIR (KBr) 3363, 2927, 2854,
1690, 1559, 1529 cmꢂ1
2921, 2851, 1684, 1632, 1533, 1471 cmꢂ1 1H NMR
;
.
((CD3)2SO) d 7.71 (m, 1H), 7.40–7.30 (m, 5H), 7.25–7.18
(m, 1H), 4.99 (s, 2H), 3.00–2.90 (m, 4H), 2.19 (t, J¼7 Hz,
2H), 2.03 (t, J¼7.1 Hz, 2H), 1.50–1.20 (m, 32H). Elemental
analysis calcd (%) for C30H50N2O5 (518): C 69.46, H 9.72, N
5.40; found: C 68.98, H 9.83, N 5.24.
4.2.1.11. CBZ-10-Et. A mixture of compound CBZ-10-
H (3.0 g, 8.94 mmol) and a catalytic amount of p-tolylsul-
fonic acid in 75 mL of ethanol and 75 mL of chloroform
was refluxed for 6 h. The reaction mixture was extracted
with water, the organic layer was dried over MgSO4 and
evaporated to dryness. Crystallization of the crude product
from petroleum ether afforded the ethyl ester CBZ-10-Et
(2.2 g, 68% yield) as a colourless solid. FTIR (KBr) 3289,
4.2.1.16. CBZ-10-10-Na. FTIR (KBr) 3314, 2921,
2851, 1685, 1641, 1558, 1533, 1471 cmꢂ1
.
2926, 2853, 1742, 1690, 1534 cmꢂ1 1H NMR (CDCl3)
;
Acknowledgements
d 7.35–7.25 (m, 5H), 5.05 (s, 2H), 4.05 (q, J¼7.15 Hz,
2H), 3.05 (t, J¼7.5 Hz, 2H), 2.25 (t, J¼7.6 Hz, 2H), 1.2–
1.5 (m, 18H). Elemental analysis calcd (%) for C21H33NO4
(363): C 69.39, H 9.15, N 3.85; found: C 69.12, H 9.43,
N 3.77.
The authors wish to thank warmly Dr. A. Colin and Dr. M.
Lescanne (University Bordeaux 1, France) for their help in
rheological measurements.
4.2.1.12. Boc-10-H. Di-tert-butyl-dicarbonate (5.74 g,
26.3 mmol) was added portionwise to a solution of 11-
aminoundecanoic acid (4.07 g, 20.2 mmol) in aqueous
NaOH (0.3 M, 130 mL) at 5 ꢀC for 3 h. The reaction mixture
was stirred at room temperature for 3 h. The gelatinous pre-
cipitate was filtered off, washed with water and suspended in
water and acidified with a few drops of concentrated HCl.
The white precipitate was filtered off and dried under
vacuum at 60 ꢀC for 5 h. Boc-10-H was used without further
purification (65% yield). FTIR (KBr) 3367, 2919, 2851,
References and notes
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1685, 1635, 1522, 1470 cmꢂ1; H NMR (CDCl3) d 4.52
(br s, 1H), 3.09 (t, J¼7 Hz, 2H), 2.35 (t, J¼7.2 Hz, 2H),
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;
(CD3OD) d 3.01 (m, 2H), 2.24 (t, 2H), 1.70–1.55 (m, 2H),
1.55–1.40 (m, 2H), 1.45–1.35 (m, 11H), 1.31 (m, 12H).
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15.3 mmol), N-hydroxysuccinimide (1.94 g, 16.8 mmol)
and DCC (4.74 g, 23 mmol) in 45 mL DMF was stirred over-
night at room temperature. After filtration, the solution was
evaporated to dryness to give the succinimidyl ester in
a quantitative yield (6.6 g) as a white solid. FTIR (KBr)
3327, 2925, 2851, 1816, 1786, 1739, 1684, 1634, 1532,
1
1470 cmꢂ1; H NMR (CDCl3) d 7.47–7.35 (m, 5H), 5.31
(s, 2H), 3.25–3.17 (m, 2H), 2.90–2.80 (m, 4H), 2.61 (t,
J¼7.1 Hz, 2H), 1.20–2.00 (m, 16H).
4.2.1.15. CBZ-10-10-H. To a solution of CBZ-10-OSu
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tion of 11-aminoundecanoic acid (1.54 g, 7.6 mmol) and
ethyl diisopropylamine (3.0 g, 23 mmol) in 20 mL DMF at
55 ꢀC. Stirring was maintained for 6 h at 50–60 ꢀC and
then for 24 h at room temperature. After the reaction mixture
was evaporated to dryness, the solid residue was taken up
with dichloromethane and filtered off. The solid was washed
several times with dichloromethane and then heated in
refluxing methanol for 4 h. The white solid was filtered
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