Expanding the gelation properties of valine-based 3,5-diaminobenzoate organogelators with N-alkylurea functionalities

Article abstract of DOI:10.3762/bjoc.6.114

A new family of valine-containing 3,5-diaminobenzoate derivatives 2 with N-alkylurea moieties attached to the valine moieties was prepared. By appending these two new N-alkylurea chains to the molecular structure, their organogelating properties were exte

Full text of DOI:10.3762/bjoc.6.114

Expanding the gelation properties of valine-based
3,5-diaminobenzoate organogelators
with N-alkylurea functionalities
Hak-Fun Chow*1,2,3 and Chin-Ho Cheng1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2010, 6, 1015–1021.
1Department of Chemistry, The Chinese University of Hong Kong,
Shatin, NT, Hong Kong SAR, 2The Center of Novel Functional
Molecules, The Chinese University of Hong Kong, Shatin, NT, Hong
Kong SAR and 3Institute of Molecular Functional Materials, Areas of
Excellence Scheme, University Grants Committee, Hong Kong SAR
doi:10.3762/bjoc.6.114
Received: 29 June 2010
Accepted: 12 October 2010
Published: 26 October 2010
Email:
Guest Editor: J.-P. Desvergne
Hak-Fun Chow* - hfchow@cuhk.edu.hk
© 2010 Chow and Cheng; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
amino acids; hydrophobic effect; organogelators; self-assembly; urea
Abstract
A new family of valine-containing 3,5-diaminobenzoate derivatives 2 with N-alkylurea moieties attached to the valine moieties was
prepared. By appending these two new N-alkylurea chains to the molecular structure, their organogelating properties were extended
from only aromatic solvents, to a wide range of other types of solvents such as alicyclic hydrocarbons, alcohols and polar solvents
such as DMSO and DMF. It was also found that a longer N-alkylurea chain conferred improved gelation power and higher thermal
stability as compared to those of the shorter ones.
Introduction
Organic gelators are an interesting group of molecules that are beforehand. Most often a subtle change of the substituents of
able to form a non-covalent three dimensional network with a the organgelator can lead to substantial modification in its
particular solvent system. The ultimate result is the immobiliza- gelating properties. This is because gelation is the result of a
tion of solvent molecules. These molecules possess many delicate balance of various driving forces. If the binding interac-
potential applications in biomedical science, environmental and tions between the organogelator molecules are too strong,
separation technology [1-6].
precipitation or crystallization will take place. On the other
hand, if the interactions are too weak, dissolution of the
One key problem in the design and synthesis of organogelators organogelator will result. In addition, non-specific interactions
lies in the difficulty in predicting their gelation properties such as hydrophobic and van der Waals interactions are diffi-
1015

Beilstein J. Org. Chem. 2010, 6, 1015–1021.
Figure 1: Amino acid based organogelators 1 and 2.
cult to quantify, yet they can play very important roles on a and DMF by replacing the Cbz group with an N-alkylurea func-
cumulative scale when such interactions actually involve a large tionality (e.g., 2). In addition, the length of the alkyl chain
ensemble of solvent and gelator molecules.
–(CH2)nMe also exhibited some interesting effects on their
gelation ability [15].
Our group has been interested in the synthesis and self-assem-
bled gelating properties of amino acid-containing non-dendritic
Results and Discussion
[7,8] and dendritic molecules [9,10]. We recently showed that Synthesis
the organogelation strength in aromatic solvents of a series of In our earlier report it was shown that, amongst the many
α-amino acid-based low molecular weight organogelators 1 α-amino acids used, valine-based 1 (R = CHMe2) possessed
(Figure 1) could be enhanced by appending additional aromatic- much better organogelating properties. Hence in the present
containing substituents [7]. Both the Cbz protecting group and study we focused only on valine derivatives 2. A homologous
the benzyl ester functionality were responsible for the enhanced series of N-alkylurea side chain derivatives 2 (n = 3–6, 9, 10,
gelating power in aromatic solvents. However, they are poor or- 12, 15, 18 and 20) was prepared in order to evaluate effect of
ganogelators in non-aromatic solvents such as alkanes, alcohols, the length of the alkyl side chain on the resulting gelation prop-
acetone, acetonitrile and DMSO. In order to further expand erties.
their gelating power in other solvents, we decided to further
modify the appending Cbz groups with other functionalities. The target organogelators were prepared according to
One particular interesting moiety is the urea group, which can Scheme 1. The known Boc protected benzyl ester 3 [7] was
act simultaneously as a donor and an acceptor of hydrogen converted into the corresponding diamino compound 4 in 98%
bonds and is known to be a key structural element in many or- yield by treatment with trifluoroacetic acid (TFA) followed by
ganogelators [11-14]. Herein we report that the organogelating neutralization with NaHCO3. The N-alkylurea derivatives 2
properties of 1 could be expanded to include alicyclic hydro- were then obtained in 88–94% as white solids by coupling com-
carbon, alcohols and even polar aprotic solvents such as DMSO pound 4 with various O-succinimidyl alkylcarbamates 6,
Scheme 1: Synthesis of organogelators 2.
1016

Beilstein J. Org. Chem. 2010, 6, 1015–1021.
prepared from the corresponding alkanoic acids 5 according to a dance of the M+ decreased with increasing length of the alkyl
literature procedure [16], in the presence of N-diisopropylethyl- hydrocarbon side chain.
amine.
Gelation properties
Structural characterization
The gelation behavior of bis(N-alkylurea valine) benzyl esters 2
All synthesized compounds were characterized by 1H and 13C were examined at a concentration of 2% w/v in various solvents
nuclear magnetic resonance spectroscopy, mass spectrometry, (Table 1). Most organogelators 2 were found to be insoluble in
elemental analysis, and optical polarimetry. Due to the poor common non-aromatic organic solvents at room temperature. In
solubilities of the target organogelators 2 in chloroform and contrast, they were soluble in aromatic solvents and organic
acetone, their 1H and 13C NMR spectra were recorded in solvents of high polarity such as 1,4-dioxane, DMF and DMSO
DMSO-d6. In addition, the 1H and 13C NMR spectra of upon warming. Interestingly, homologues having shorter ali-
analogues with thirteen or more carbon atoms in the aliphatic phatic chain (n < 10) were poor organogelators, while the
hydrocarbon chains were recorded at 100 °C to avoid gelation longer aliphatic chain analogues (n ≥ 10) formed transparent
of the solvent. The 1H NMR spectra of compounds 2 showed gels in aromatic solvents and translucent gels in 1,4-dioxane,
the presence of the aliphatic hydrocarbon chains and the urea DMF and DMSO. Most interestingly, it was observed that
moieties. The methyl group of the aliphatic chains appeared as a organogelator 2 (n = 20) with the longest hydrocarbon chain
triplet at ~ δ 0.86, while the methylenes of the aliphatic chains also formed opaque gels in alcoholic solvents and translucent
were located in close proximity to the signals of the valine side gels in alicyclic hydrocarbon solvents, respectively. Hence, the
chain. On the other hand, the signals from the isopropyl group range of the solvents that these new compounds can gel was
of the valine residue overlapped with those of the methylenes of significantly expanded by replacing the Cbz group with an
the aliphatic chains. The two NH protons of the urea groups N-alkylurea functionality.
were different and appeared as a doublet at δ 6.04 and a triplet
at δ 6.07. The benzyl ester group appeared as a singlet at δ 5.24 Based on these experiments, organogelators 2 with longer ali-
and a set of multiplets at δ 7.35–7.47. Finally, the aromatic phatic hydrocarbon chains (n ≥ 10) were found to exhibit better
protons of the 3,5-diaminobenzoate moiety appeared as two gelation behavior in aromatic solvents. However, it was
singlets at δ 7.98 and δ 8.26.
interesting to note that compounds with less than or equal to
eight carbon atoms in the side chain failed to induce gelation.
The 13C NMR signals of the target molecules 2 could be The effect of aliphatic hydrocarbon chain length (n = 10, 12, 15,
grouped into three separate regions. First, in the downfield 18 and 20) on their gelation power was then compared by the
region, the 13C signals located at δ 157, 165 and 171 were determination of their minimum gelation concentration (MGC)
attributed to the urea, ester and anilide C=O groups, respective- and gel-sol transition temperature (Tg) in different solvents
ly. Second, the 13C signals of the central 3,5-diamino-substi- (Table 2). It was found that the longer the alkyl chain, the lower
tuted aromatic core were scattered between δ 110–140, while the MGC but the higher the Tg value. Hence, the cumulative
the aromatic signals due to the benzyl ester were found at ~ δ hydrophobic interaction between organogelator molecules with
127–135. Finally, the 13C signals of the valine side chain and longer aliphatic chains must be stronger than that of the shorter
the aliphatic hydrocarbon side chain were located in a range of ones, and this factor should contribute to the higher thermal
δ 12–66. Specifically, the 13C signal situated at δ 58 corres- stability of the longer chain organogels. In addition, the pres-
ponded to the valine α-carbon. The benzylic carbon appeared at ence of the long aliphatic chain also prevented the organogel-
δ 66. The remaining aliphatic 13C signals due to the aliphatic ators from crystallizing by imposing a higher degree of local
carbons and some of the resonance peaks overlapped with each disorder.
other. Hence, the number of the observed signals was some-
times less than theoretically predicted. One 13C signal (CH2NH) Fourier transform infrared spectroscopy (FT-IR) was employed
was located at δ 39 and was often buried within the residual to elucidate the extent of intermolecular hydrogen bonding in
solvent signals of DMSO-d6. For organogelators with longer the different macroscopic phases of organogelator 2 (n = 20) in
aliphatic chains, this signal was too weak to be observed and o-xylene (Table 3). In 1% w/v hot o-xylene solution (100 °C),
assignment could only be made based on the chemical shift two peaks at 3342 and 3247 cm−1 in the νN–H regions were
value of other homologues where this signal could be observed. identified. These two signals could be assigned to the stretching
bands of urea N–H and anilide N–H, respectively. The two
High-resolution mass spectra were recorded for all synthesized peaks at 1729 and 1629 cm−1 in the νC=O region were found
compounds. The experimental determined M+ results were in and they were attributed to the anilide C=O and urea C=O, res-
accordance with the theoretical values. Generally, the abun- pectively. Signal assignments of the urea C=O and N–H were
1017

Beilstein J. Org. Chem. 2010, 6, 1015–1021.
Table 1: Gelation behavior of bis(N-alkylurea valine) compounds 2 at 2% w/v a.
Solvent
2 (n = 3–6)
2 (n = 9)
2 (n = 10)
2 (n = 12)
2 (n = 15)
2 (n = 18)
2 (n = 20)
THF
I
P
I
P
P
P
P
P
acetone
I
I
I
I
I
I
chloroform
dichloromethane
ethyl acetate
ethylene glycol
1-butanol
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
–
–
–
–
I
–
–
–
–
–
OG
OG
OG
TG
I
1-heptanol
1-dodecanol
cyclooctanol
hexane
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
I
I
I
I
I
cyclohexene
cyclooctene
1,4-dioxane
DMF
–
–
S
S
S
S
S
S
S
S
S
S
–
–
–
–
–
TG
TG
TG
TG
TG
CG
CG
CG
CG
TG
CG
CG
–
–
–
–
–
S
S
S
S
S
CG
CG
S
CG
CG
S
TG
TG
TG
CG
CG
CG
CG
TG
CG
CG
TG
TG
TG
CG
CG
CG
CG
TG
CG
CG
TG
TG
TG
CG
CG
CG
CG
TG
CG
CG
S
DMSO
TG
CG
S
anisole
benzene
benzyl alcohol
o-dichlorobenzene
nitrobenzene
toluene
CG
CG
TG
CG
CG
o-xylene
aI = insoluble; P = precipitation; S = soluble; CG = clear transparent gel; OG = opaque gel; TG = translucent gel.
based on the spectral data of a model compound, namely 1,3- property of the urea moiety. In addition, broadening of absorp-
didodecylurea. In the FT-IR spectrum of 2 (n = 20) (1% w/v) in tion signals in the gel state was observed which suggests that
o-xylene gel at 25 °C, the corresponding peaks were identified further intermolecular hydrogen bonding occurred during gel
at 3335, 3268, 1728 and 1628 cm−1, respectively. Hence, there formation.
was little difference in terms of the stretching frequencies both
in solution and in the gel state. Furthermore, both sets of values Conclusion
are very similar to those of 2 (n = 20) in solid KBr, where the We have reported the synthesis of novel valine-containing 3,5-
C=O and N–H moieties are known to form extensive intermole- diaminobenzoate derivatives 2 with additional N-alkylurea
cular hydrogen bonds. Hence, it is very likely that compound 2 functionality at the N-terminal of the valine residues. The
exists as aggregates via intermolecular hydrogen bonding in resulting organogelators were found to possess gelating ability
solution state due to the extremely strong hydrogen bonding that covered a wider range of organic solvents, including alco-
Table 2: Minimum gelation concentration and gel-to-sol transition temperature of compounds 2 (n = 10, 12, 15, 18 and 20).
Solvent
2 (n = 10)
2 (n = 12)
2 (n = 15)
2 (n = 18)
2 (n = 20)
MGCa Tgb
MGC
Tg
MGC
Tg
MGC
Tg
MGC
Tg
benzyl alcohol
o-dichlorobenzene
o-xylene
1.8
1.5
1.6
—
—
—
1.8
1.2
1.5
70
1.5
1.3
1.5
79
1.2
1.0
1.0
88
1.0
0.8
1.0
94
109
75
113
80
116
83
120
86
aIn w/v%; bIn °C as determined by inverted tube method.
1018

Beilstein J. Org. Chem. 2010, 6, 1015–1021.
Table 3: FT-IR data of compound 2 (n = 20) and 1,3-di(dodecyl)ureaa.
Samples
urea N–H
anilide N–H
anilide C=O
urea C=O
2 (n = 20) in o-xylene solution at 100 °C
2 (n = 20) in o-xylene gel at 25 °C
2 (n = 20) in solid in KBr pellet
3342
3335
3348
3340
3247
3268
3248
—
1729
1728
1730
―
1629
1628
1629
1622
1,3-di(dodecyl)urea in solid KBr pellet
ain cm−1.
holic, aromatic, alicyclic hydrocarbon and polar solvents. was added to a THF solution (100 mL) of the diamino benzyl
Furthermore, attachment of longer aliphatic chains not only ester 4 (2.2 g, 5.0 mmol). The reaction mixture was stirred at 25
enhanced hydrophobic interactions between the organogelators, °C for 4 h. The insoluble crude solid product was filtered and
but also prevented crystallization of the self assembled aggre- washed successively with boiling n-hexane (100 mL), acetone
gates during gelation, producing gels with a higher Tg and a (100 mL) and THF (100 mL) to afford the title compound.
lower MGC value.
2 (n = 3). The product was obtained as a white solid (3.0 g,
Experimental
94%) from O-succinimidyl butylcarbamate 6 (n = 3) (2.2 g,
General. Optical rotation measurements were conducted in 10.0 mmol). [α]D = +62.4 (c 1.01). mp 221–222 °C. 1H NMR
DMSO (unless otherwise stated) and below the MGC to avoid (DMSO-d6): δ 0.83–0.90 (18H, m, CH(CH3)2 and
molecular aggregation or gelation and were measured with a CH2CH2CH3), 1.22–1.36 (8H, m, aliphatic H), 1.92–1.94 (2H,
Perkin Elmer 341 polarimeter. The starting materials 6 were m, CHCH(CH3)2), 2.99 (4H, q, J = 6, NHCH2CH2), 4.18 (2H,
prepared according to a literature procedure [16]. General pro- dd, J = 8.7 and 6.6, NHCHCH), 5.34 (2H, s, PhCH2), 6.05 (2H,
cedures, yields and characterization data of compounds 6 (n = d, J = 4.2, urea NH), 6.09 (2H, t, J = 5.6, urea NH), 7.35–7.47
3–20) can be found in Supporting Information File 1.
(5H, m, ArH), 7.99 (2H, s, ArH), 8.28 (1H, s, ArH), 10.30 (2H,
s, CONHAr). 13C NMR (DMSO-d6): δ 13.7, 17.9, 19.3, 19.5,
Compound 4. Trifluoroacetic acid (50 mL, 60 mmol) was 31.2, 32.1, 38.9, 58.7, 66.4, 114.4, 114.8, 128.2, 128.4, 128.6,
added to a solution of the benzyl ester 3 [2] (6.40 g, 10.0 mol) 130.3, 136.0, 139.6, 157.9, 165.4, 171.8. MS (FAB) 639 (M +
in CH2Cl2 (100 mL) at 25 °C. The progress of deprotection was H+, 12%). HRMS (LSIMS): calcd for C34H50N6O6, 639.3865;
monitored by TLC. Upon complete deprotection (~ 12 h), the found, 639.3854. Anal. found: C, 63.75; H, 7.95; N, 13.08.
solvent was removed on a rotary evaporator. The crude product C34H50N6O6 requires C, 63.93; H, 7.89; N, 13.15.
was made alkaline by the addition of aqueous NaHCO3 solu-
tion to pH 8. The mixture was extracted with CH2Cl2 2 (n = 4). The compound was obtained as a white solid (3.1 g,
(50 mL × 3), the combined organic layers were washed with 94%) from O-succinimidyl pentylcarbamate 6 (n = 4) (2.3 g,
saturated NaCl solution (100 mL × 2), dried (MgSO4), filtered 10.0 mmol). [α]D = +57.9 (c 1.08). mp 224–225 °C. 1H NMR
and concentrated in vacuo to give compound 4 as a pale yellow (DMSO-d6): δ 0.82–0.90 (18 H, m, CH(CH3)2 and
liquid (4.3 g, 98%). [α]D20 −177.6 (c 0.50, CHCl3). 1H NMR CH2CH2CH3), 1.20–1.39 (12 H, m, aliphatic H), 1.91–1.95
(DMSO-d6): δ 0.85 (6H, d, J = 6.9, CH(CH3)Me), 0.91 (6H, d, (2H, m, CHCH(CH3)2), 2.97 (4H, q, J = 6, NHCH2CH2), 4.16
J = 6.9, CH(Me)CH3), 1.85–1.99 (2H, m, CH(CH3)2), 3.12 (2H, (2H, dd, J = 9.0 and 6.6, NHCHCH), 5.34 (2H, s, PhCH2), 6.05
d, J = 5.7, H2NCHCH), 3.2–3.5 (6H, brs, NH), 5.35 (2H, s, (2H, d, J = 4.5, urea NH), 6.08 (2H, t, J = 5.6, urea NH),
PhCH2), 7.36–7.49 (5H, m, ArH), 7.98 (2H, d, J = 1.8, ArH), 7.38–7.48 (5H, m, ArH), 7.98 (2H, s, ArH), 8.26 (1H, s, ArH),
8.35 (1H, t, J = 1.8, ArH). 13C NMR (DMSO-d6): δ 17.4, 19.5, 10.30 (2 H, s, CONHAr). 13C NMR (DMSO-d6): δ 13.9, 17.9,
31.8, 60.8, 66.4, 114.4, 114.7, 128.2, 128.4, 128.6, 130.3, 136.1, 19.3, 21.9, 28.6, 29.6, 31.2, 39.2, 58.7, 66.4, 114.4, 114.8,
139.6, 165.4, 174.1. MS (FAB): 441 (M + H+, 30%). HRMS 128.1, 128.2, 128.6, 130.3, 136.0, 139.6, 157.9, 165.3, 171.8.
(LSIMS): calcd for C24H32N4O4, 441.2496; found, 441.2505. MS (FAB) 667 (M + H+, 10%). HRMS (LSIMS): calcd for
Anal. found: C, 65.63; H, 7.50; N, 12.71. C24H32N4O4 requires C36H54N6O6, 667.4178; found, 667.4185. Anal. found: C,
C, 65.43; H, 7.32; N, 12.71.
64.77; H, 8.20; N, 12.53. C36H54N6O6 requires C, 64.84; H,
8.16; N, 12.60.
General procedure for the preparation of bis-(N-alkylurea)
benzyl esters 2. A mixture of O-succinimidyl carbamate 6 2 (n = 5). The product was obtained as a white solid (3.2 g,
(10.0 mmol) and diisopropylethylamine (1.8 mL, 10.0 mmol) 91%) from O-succinimidyl hexylcarbamate 6 (n = 5) (2.4 g,
1019

Beilstein J. Org. Chem. 2010, 6, 1015–1021.
10.0 mmol). [α]D = +63.6 (c 0.99). mp 225–226 °C. 1H NMR (DMSO-d6): δ 0.81–0.90 (18H, m, CH(CH3)2 and
(DMSO-d6): δ 0.79–0.89 (18H, m, CH(CH3)2 and CH2CH2CH3), 1.22–1.34 (36H, m, aliphatic H), 1.91–1.97 (2H,
CH2CH2CH3), 1.21–1.35 (16H, m, aliphatic H), 1.89–1.96 (2H, m, CHCH(CH3)2), 2.97 (4 H, q, J = 6, NHCH2CH2), 4.18 (2H,
m, CHCH(CH3)2), 2.95 (4H, q, J = 6, NHCH2CH2), 4.17 (2H, dd, J = 8.7 and 6.6, NHCHCH), 5.34 (2H, s, PhCH2), 6.04 (2H,
dd, J = 8.4 and 6.6, NHCHCH), 5.31 (2H, s, PhCH2), 6.00 (2H, d, J = 5.4, urea NH), 6.07 (2H, t, J = 5.3, urea NH), 7.35–7.47
d, J = 9, urea NH), 6.04 (2H, t, J = 5.6, urea NH), 7.32–7.44 (5H, m, ArH), 7.98 (2H, s, ArH), 8.26 (1H, s, ArH), 10.27 (2H,
(5H, m, ArH), 7.96 (2H, s, ArH), 8.24 (1H, s, ArH), 10.20 (2H, s, CONHAr). 13C NMR (DMSO-d6): δ 14.0, 18.0, 19.4, 22.2,
s, CONHAr). 13C NMR (DMSO-d6): δ 13.9, 17.9, 19.3, 22.1, 26.5, 28.8, 28.9, 29.1, 29.2, 30.1, 30.8, 31.3, 31.4, 39, 58.9,
26.1, 29.9, 31.0, 31.2, 39, 58.7, 66.4, 114.4, 114.8, 128.1, 128.4, 66.5, 114.6, 114.9, 128.2, 128.3, 128.7, 130.4, 136.1, 139.7,
128.5, 130.3, 136.0, 139.6, 157.9, 165.4, 171.8. MS (FAB) 695 158.1, 165.5, 171.9. MS (FAB) 836 (M + H+, 5%). HRMS
(M + H+, 12%). HRMS (LSIMS): calcd for C38H58N6O6, (LSIMS): calcd for C48H78N6O6, 835.6056; found, 835.6041.
695.4491; found, 695.4501. Anal. found: C, 65.26; H, 8.43; N, Anal. found: C, 68.67; H, 9.45; N, 10.05. C48H78N6O6 requires
11.81. C38H58N6O6 requires C, 65.68; H, 8.41; N, 12.09.
C, 69.03; H, 9.41; N, 10.06.
2 (n = 6). The product was obtained as a white solid (3.4 g, 2 (n = 12). The product was obtained as a white solid (4.0 g,
94%) from O-succinimidyl heptylcarbamate 6 (n = 6) (2.6 g, 90%) from O-succinimidyl tridecylcarbamate 6 (n = 12) (3.4 g,
10.0 mmol). [α]D = +59.7 (c 1.05). mp 227–228 °C. 1H NMR 10.0 mmol). [α]D = +53.9 (c 0.99). mp 235–236 °C. 1H NMR
(DMSO-d6): δ 0.81–0.91 (18H, m, CH(CH3)2 and (DMSO-d6, 100 °C): δ 0.82–0.90 (18 H, m, CH(CH3)2 and
CH2CH2CH3), 1.23–1.37 (20H, m, aliphatic H), 1.90–1.97 (2H, CH2CH2CH3), 1.23–1.35 (44H, m, aliphatic H), 1.91–1.98 (2H,
m, CHCH(CH3)2), 2.98 (4H, q, J = 6, NHCH2CH2), 4.18 (2H, m, CHCH(CH3)2), 2.99 (4H, q, J = 7, NHCH2CH2), 4.18 (2H,
dd, J = 9.0 and 6.6, NHCHCH), 5.34 (2H, s, PhCH2), 6.04 (2H, dd, J = 9.0 and 6.6, NHCHCH), 5.34 (2H, s, PhCH2), 6.02 (2H,
d, J = 9.3, urea NH), 6.07 (2H, t, J = 5.7, urea NH), 7.35–7.48 d, J = 9.6, urea NH), 6.05 (2H, t, J = 6.2, urea NH), 7.35–7.47
(5H, m, ArH), 7.99 (2H, s, ArH), 8.27 (1H, s, ArH), 10.26 (2H, (5H, m, ArH), 7.98 (2H, s, ArH), 8.26 (1H, s, ArH), 10.20 (2H,
s, CONHAr). 13C NMR (DMSO-d6): δ 13.9, 17.9, 19.3, 22.0, s, CONHAr). 13C NMR (DMSO-d6, 100 °C): δ 13.0, 17.3, 18.5,
26.3, 28.4, 30.0, 31.2, 31.3, 39, 58.7, 66.3, 114.4, 114.8, 128.1, 21.3, 25.8, 27.9, 28.1, 28.3, 29.3, 30.4, 30.6, 39, 58.7, 65.7,
128.4, 128.5, 130.3, 136.0, 139.6, 157.9, 165.3, 171.8. MS 114.9, 115.0, 127.2, 127.4, 127.8, 130.0, 135.7, 138.9, 157.4,
(FAB) 723 (M + H+, 5%). HRMS (LSIMS): calcd for 164.9, 171.0. MS (FAB) 892 (M + H+, 3%). HRMS (LSIMS):
C40H62N6O6, 723.4804; found, 723.4819. Anal. found: C, calcd for C52H86N6O6, 891.6682; found, 891.6691. Anal.
66.42; H, 8.68; N, 11.63. C40H62N6O6 requires C, 66.45; H, found: C, 69.95; H, 9.79; N, 9.47. C52H86N6O6 requires C,
8.64; N, 11.62.
70.08; H, 9.73; N, 9.42.
2 (n = 9). The product was obtained as a white solid (3.7 g, 2 (n = 15). The product was obtained as a white solid (4.2 g,
92%) from O-succinimidyl decylcarbamate 6 (n = 9) (3.0 g, 89%) from O-succinimidyl hexadecylcarbamate 6 (n = 15)
10.0 mmol). [α]D = +53.9 (c 1.00). mp 230–231 °C. 1H NMR (3.8 g, 10.0 mmol). [α]D = +50.5 (c 1.05). mp 239–240 °C. 1H
(DMSO-d6): δ 0.82–0.91 (18H, m, CH(CH3)2 and NMR (DMSO-d6, 100 °C): δ 0.86 (6H, t, J = 3.5,
CH2CH2CH3), 1.22–1.35 (32H, m, aliphatic H), 1.91–1.97 (2H, CH2CH2CH3), 0.91 (6H, d, J = 6.9, CH(CH3)Me), 0.94 (6H, d,
m, CHCH(CH3)2), 2.98 (4 H, q, J = 6, NHCH2CH2), 4.18 (2H, J = 6.9, CHMe(CH3)), 1.26–1.40 (56H, m, aliphatic H),
dd, J = 9.0 and 6.6, NHCHCH), 5.34 (2H, s, PhCH2), 6.03 (2H, 1.90–2.15 (2H, m, CHCH(CH3)2), 2.95–3.06 (4H, m,
d, J = 8.7, urea NH), 6.06 (2H, t, J = 3.8, urea NH), 7.35–7.47 NHCH2CH2), 4.19 (2H, dd, J = 6.3 and 9, NHCHCH), 5.36
(5H, m, ArH), 7.99 (2H, s, ArH), 8.26 (1H, s, ArH), 10.23 (2 H, (2H, s, PhCH2), 5.86 (2H, d, J = 9, urea NH), 5.93 (2H, t, J =
s, CONHAr). 13C NMR (DMSO-d6): δ 13.9, 17.9, 19.3, 22.1, 5.4, urea NH), 7.37–7.47 (5H, m, ArH), 7.95 (2H, d, J = 2.1,
26.4, 28.7, 28.8, 28.9, 29.0, 30.0, 31.3, 39, 58.7, 66.3, 114.4, ArH), 8.26 (1H, t, J = 2.1, ArH), 9.90 (2H, s, CONHAr). 13C
114.8, 128.1, 128.2, 128.5, 130.3, 136.0, 139.5, 157.9, 165.3, NMR (DMSO-d6, 100 °C): δ 13.0, 17.3, 18.6, 21.3, 25.8, 28.0,
171.8. MS (FAB) 808 (M + H+, 5%). HRMS (LSIMS): calcd 28.2, 28.4, 29.4, 30.5, 30.6, 39, 58.6, 65.7, 114.87, 114.93,
for C46H74N6O6, 807.5743; found, 807.5730. Anal. found: C, 127.3, 127.4, 127.9, 130.0, 135.7, 139.0, 157.5, 164.9, 171.0.
67.97; H, 9.24; N, 10.39. C46H74N6O6 requires C, 68.45; H, MS (FAB) 976 (M + H+, 5%). HRMS (LSIMS): calcd for
9.24; N, 10.41.
C58H98N6O6, 975.7621; found, 975.7626. Anal. found: C,
71.46; H, 9.94; N, 8.35. C58H98N6O6 requires C, 71.42; H,
2 (n = 10). The product was obtained as a white solid (3.8 g, 10.13; N, 8.61.
91%) from O-succinimidyl undecylcarbamate 6 (n = 10) (3.1 g,
10.0 mmol). [α]D = +52.3 (c 1.02). mp 232–233 °C. 1H NMR
1020

Beilstein J. Org. Chem. 2010, 6, 1015–1021.
2. van Esch, J. H.; Feringa, B. L. Angew. Chem., Int. Ed. 2000, 39,
2263–2266.
2 (n = 18). The product was obtained as a white solid (4.7 g,
88%) from O-succinimidyl nonadecylcarbamate 6 (n = 18) (4.3
g, 10.0 mmol). [α]D = +52.5 (c 1.01). mp 243–244 °C. 1H NMR
(DMSO-d6, 100 °C): δ 0.84–0.93 (18H, m, CH(CH3)2 and
CH2CH2CH3), 1.25–1.37 (68H, m, aliphatic H), 1.95–1.99 (2H,
m, CHCH(CH3)2), 2.95–3.06 (4H, m, NHCH2CH2), 4.19 (2H,
dd, J = 8.4 and 6.6, NHCHCH), 5.35 (2H, s, PhCH2), 5.92 (2H,
d, J = 8.7, urea NH), 5.98 (2H, t, J = 5.6, urea NH), 7.35–7.47
(5H, m, ArH), 7.96 (2H, s, ArH), 8.24 (1H, s, ArH), 10.04 (2H,
s, CONHAr). 13C NMR (DMSO-d6, 100 °C): δ 13.0, 17.3, 18.6,
doi:10.1002/1521-3773(20000703)39:13<2263::AID-ANIE2263>3.0.CO
;2-V
3. Gronwald, O.; Snip, E.; Shinkai, S. Curr. Opin. Colloid Interface Sci.
2002, 7, 148–156. doi:10.1016/S1359-0294(02)00016-X
4. Sangeetha, N. M.; Maitra, U. Chem. Soc. Rev. 2005, 34, 821–836.
doi:10.1039/b417081b
5. Dastidar, P. Chem. Soc. Rev. 2008, 37, 2699–2715.
doi:10.1039/b807346e
6. Vintiloiu, A.; Leroux, J.-C. J. Controlled Release 2008, 125, 179–192.
doi:10.1016/j.jconrel.2007.09.014
21.3, 25.8, 28.0, 28.2, 28.4, 29.4, 30.5, 30.6, 39, 58.6, 65.7, 7. Chow, H.-F.; Zhang, J.; Lo, C.-M.; Cheung, S.-Y.; Wong, K.-W.
Tetrahedron 2007, 63, 363–373. doi:10.1016/j.tet.2006.10.066
114.87, 114.93, 127.3, 127.4, 127.9, 130.0, 135.7, 139.0, 157.5,
8. Chow, H.-F.; Wang, G.-X. Tetrahedron 2007, 63, 7407–7418.
164.9, 171.0. MS (FAB) 1060 (M + H+, 3%). HRMS (LSIMS):
doi:10.1016/j.tet.2007.02.037
calcd for C64H110N6O6, 1069.8560; found, 1069.8550. Anal.
9. Chow, H.-F.; Zhang, J. Chem.–Eur. J. 2005, 11, 5817–5831.
found: C, 72.53; H, 10.57; N, 7.81. C64H110N6O6 requires C,
doi:10.1002/chem.200500174
72.55; H, 10.46; N, 7.93.
10.Chow, H.-F.; Zhang, J. Tetrahedron 2005, 61, 11279–11290.
doi:10.1016/j.tet.2005.08.006
11.Steed, J. W. Chem. Soc. Rev. 2010, 39, 3686–3699.
doi:10.1039/b926219a
2 (n = 20). The product was obtained as a white solid (4.8 g,
86%) from O-succinimidyl heneicosylcarbamate 6 (n = 20) (4.5
g, 10.0 mmol). [α]D = +53.1 (c 1.00). mp 249–250 °C. 1H NMR
(DMSO-d6, 100 °C): δ 0.86 (6H, t, J = 6.9, CH2CH2CH3), 0.92
(6H, d, J = 6.9, CH(CH3)Me), 0.95 (6H, d, J = 6.9,
CHMe(CH3)), 1.28–1.43 (76H, m, aliphatic H), 1.95–2.12 (2H,
m, CHCH(CH3)2), 3.00 (4H, q, J = 6, NHCH2CH2), 4.19 (2H,
dd, J = 8.1 and 6.6, NHCHCH), 5.36 (2H, s, PhCH2), 5.82 (2H,
d, J = 9, urea NH), 5.88 (2H, t, J = 5.6, urea NH), 7.37–7.47
(5H, m, ArH), 7.94 (2H, d, J = 2.1, ArH), 8.19 (1H, t, J = 1.8,
ArH), 9.80 (2H, s, CONHAr). 13C NMR (DMSO-d6, 100 °C): δ
13.0, 17.3, 18.5, 20.2, 21.3, 25.8, 27.9, 28.1, 28.3, 29.3, 30.4,
30.6, 39, 58.7, 65.7, 114.9, 115.0, 127.2, 127.4, 127.8, 130.0,
135.7, 138.9, 157.5, 164.9, 171.0. MS (FAB) 1116 (M + H+,
100%). HRMS (LSIMS): calcd for C68H118N6O6, 1115.9186;
found, 1115.9192. Anal. found: C, 73.17; H, 10.53; N, 7.45.
C68H118N6O6 requires C, 73.20; H, 10.66; N, 7.53.
12.van Esch, J.; Kellogg, R. M.; Feringa, B. L. Tetrahedron Lett. 1997, 38,
281–284. doi:10.1016/S0040-4039(96)02292-7
13.van Esch, J.; de Feyter, S.; Kellogg, R. M.; de Schryver, F.;
Feringa, B. L. Chem.–Eur. J. 1997, 3, 1238–1243.
doi:10.1002/chem.19970030811
14.van de Laan, S.; Feringa, B. L.; Kellogg, R. M.; van Esch, J. Langmuir
2002, 18, 7136–7140. doi:10.1021/la025561d
15.George, M.; Tan, G.; John, V. T.; Weiss, R. G. Chem.–Eur. J. 2005, 11,
3243–3254. doi:10.1002/chem.200401066
16.Guichard, G.; Semetey, V.; Didierjean, C.; Aubry, A.; Briand, J. P.;
Rodriguez, M. J. Org. Chem. 1999, 64, 8702–8705.
doi:10.1021/jo990092e
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Supporting Information
General procedure, yields and characterization data of
compounds 6 (n = 3–20).
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
Supporting Information File 1
Experimental Part.
(http://www.beilstein-journals.org/bjoc)
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-6-114-S1.pdf]
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.6.114
References
1. Terech, P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133–3159.
doi:10.1021/cr9700282
1021