Synthesis and characterization of d-glucosamine-derived low molecular weight gelators

Article abstract of DOI:10.1016/j.tet.2010.05.071

Carbohydrate-based low molecular weight gelators are an interesting class of molecules with many potential applications. Previously, we have found that certain esters and carbamates of 4,6-O-benzylidene-α-d-methyl- glucopyranoside are low molecular weight

Full text of DOI:10.1016/j.tet.2010.05.071

Tetrahedron 66 (2010) 5962e5971
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and characterization of -glucosamine-derived low molecular
D
weight gelators
1
1
*
Navneet Goyal , Sherwin Cheuk , Guijun Wang
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Carbohydrate-based low molecular weight gelators are an interesting class of molecules with many
Received 21 April 2010
Accepted 17 May 2010
Available online 1 July 2010
potential applications. Previously, we have found that certain esters and carbamates of 4,6-O-benzylidene-
a-
D
-methyl-glucopyranoside are low molecular weight gelators for a variety of solvents, including water. In
order to obtain effective and robust sugar-based organogelators and understand the structure and gelation
relationship, we extended our studies using 4,6-O-benzylidene- -methyl-2-deoxy-2-amino-glucopyr-
anoside as the headgroup. A series of amides and ureas were prepared from the protected -glucosamine
a-D
Keywords:
D
Hydrogelator
Organogelator
Glucosamine
Carbohydrate
Self-assembling
and the corresponding isocyanates or acid chlorides, in good yields. The self-assembling properties of these
compounds were studied in several solvents, including water and aqueous solutions. Comparing to the
ester and carbamate derivatives previously prepared from D-glucose, the amides and urea derivatives
afforded more robust gels at lower concentrations typically. Most of these compounds were found to be
efficient low molecular weight hydrogelators (LMHGs) for aqueous solutions at concentrations lower than
0.5 wt %. The preparation and characterization of these compounds are reported here.
Ó 2010 Published by Elsevier Ltd.
1. Introduction
organogelators is of great interests to us.11e14 Previously, we had
found that various derivatives of 4,6-O-benzylidene-methyl-a-D-
In recent years, low molecular weight gelators (LMWGs) have
gained great attention because of their potential applications as
advanced soft materials. LMWGs are small molecules that are
able to form reversible gels in organic solvents or aqueous
solutions. These compounds are able to self-assemble and form
three-dimensional networks by solely non-covalent forces, such
glucopyranose exhibited good gelation properties.11e13 A series of
esters and carbamates were synthesized and studied systemati-
cally, and we found that certain structural features are important
for forming gels in aqueous solutions of DMSO or ethanol. For ex-
ample, compounds with the general structure 1 exhibited good
gelation in polar solvents when the R group is a short alkyl chain
with terminal acetylene function.11 In monoesters 1, the free hy-
droxyl group can function as hydrogen bond donor and facilitates
the self-assembling. The carbamate derivatives 2 were more effi-
cient gelators compared to the esters and the R group tolerated
a broader range of functional groups, typically these compounds
were able to form gels at lower concentrations. We also synthesized
several carbamate derivatives with the general structure 3, these
compounds generally showed gelation capability in aqueous mix-
tures. The improved gelation efficacy for carbamates is attributed to
the additional hydrogen bonding donor NH group (Fig. 1).14
as hydrogen bonding,
pep stacking, hydrophobic interactions,
etc. The resulting gels are usually called supramolecular gels or
physical gels to differentiate from polymer gels. There has been
much effort in discovering effective LMWGs and understanding
the gelation phenomenon.1e5 LMWGs encompass broad structure
classes and are often discovered by serendipity. Carbohydrates
are naturally abundant renewable resources, which are useful in
the preparation of chiral intermediates and advanced materials.
The dense chiral hydroxyl groups present in carbohydrates can be
regioselectively functionalized to form interesting self-assembled
supramolecular structures including LMWGs. Sugar-based
organogelators have been found to be versatile materials for drug
delivery, enzyme immobilization, etc.6e10
The carbamates 3 were synthesized using the protected D-glu-
cosamine 4 as the headgroup.15,16 Based on the improved gelation
for carbamates, it is reasonable to expect that other types of de-
rivatives of compound 4 such as amides and ureas may offer even
better gelation results. Urea derivatives have been studied exten-
sively as organogelators. Much of their gelation ability stems from
the one-dimensional hydrogen bonding array formed by the urea
functional groups.17e37 This allows the molecules to self-assemble in
a highly ordered fashion. Though they are not as extensively studied
The modification of simple carbohydrate derivatives to
obtain effective low molecular weight hydrogelators and
* Corresponding author. Tel.: þ1 504 280 1258; fax: þ1 504 280 6860; e-mail
address: gwang2@uno.edu (G. Wang).
1
The two authors, Goyal N. and Cheuk S. contributed equally.
0040-4020/$ e see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tet.2010.05.071

N. Goyal et al. / Tetrahedron 66 (2010) 5962e5971
5963
Ph
O
amides synthesized and their gelation properties in several
solvents are summarized in Table 1. These functional groups were
chosen partially based on the structural information obtained from
the ester derivatives. We expected that the additional hydrogen
bonding unit would allow a wider range of the hydrophobic tail R
groups to afford gels because of the potential for enhanced
hydrogen bonding interactions. Therefore, a broader series of acyl
groups were selected here. These include the straight chain analogs
with 5e8 carbons 10e13, compounds with terminal acetylene
functional groups 14e17, compounds with alkene groups 18 and 19,
compounds with halogens 20 and 21, and aromatic derivatives 22
and 23. After their preparation, these compounds were screened
for their gelation properties (Table 1).
Ph
O
O
NH
O
Ph
Ph
O
O
O
O
O
HO
O
HO
HO
O
OMe
OMe
NH
O
O
OMe
O
O
R
R
O
R
3
1
2
Ph
O
O
O
Ph
O
O
O
O
O
HO
O
HO
HO
NH
OMe
NH
NH
R
2OMe
OMe
O
NH
4
5
6
R
From Table 1, most of the compounds were able to form stable gels
in 33% aqueous solutions of DMSO or ethanol at concentrations lower
than 5.0 mg/mL. Several compounds also formed gels in ethanol and
fewer formed gels in hexane or water. These results are different than
the ones obtained from the glucose ester derivatives, in which a ma-
jority of the alkynyl 2-esters were able to gelate both hexane and
water.11 The presence of the amide bonds, especially the NH bond, is
important in the formation of the self-assembled networks. Similar to
theglucoseesterderivatives, thealkylchainplays animportantrolein
gelation. We found that amides containing chains that were 6e8
carbons in length formed very stable gels at relatively low concen-
trations. Typically, the amides formed robust and translucent gels
(FigureS1). Forexample, thehexylamideformedgelsthatwerestable
for several months in closed containers. The gels can be reformed
repeatedly by reheating and sonication of the solution phases. The
abilityof thesevariousamidestoform stablegels inaqueousmixtures
might arise from a hydrogen bonding interaction of the amide bonds
with the solvents. Ethanol and DMSO can aid in self-assembly by
solvating the hydrophobic regions of the LMOGs, disrupting the
crystalline packing, and thus forming gels. In addition, the
compounds and the solvents have a certain ‘matched’ hydrophobicity
and hydrophilicity, in that ethanol and DMSO can help to stabilize the
gels by interacting with both regions in the amides.
For the aliphatic derivatives, the amides with saturated alkyl
chains (10e13) are quite versatile and efficient LMOGs that are able
to efficiently gelate a range of solvents, including hexane and
aqueous mixtures of ethanol and DMSO, but not pure water. The
compounds with 6e8 carbon chains (11e13) are the most efficient
gelators. The alkynyl derivatives exhibit a similar trend, in that
a longer chain is somewhat more favorable than a shorter chain;
compounds 15e17 are good gelators for aqueous solutions of DMSO
and EtOH. The hexynyl compound 16 proved to be the most
efficient, forming stable gels in ethanol/water at 0.7 mg/mL. For the
Figure 1. General structures of several D-glucose and D-glucosamine derivatives.
as the ureas, amides can also form hydrogen bonding arrays, and are
also used often in the design and synthesis of low molecular weight
gelators.38e42 Therefore, with the proper selection of alkyl groups,
the amide and urea derivatives 5 and 6 are expected to be good
hydrogelators or organogelators. The structure information
obtained from our studies of the glucose-based gelators 1, 2, and 3
can help us to select suitable substituents for the amino group.
2. Results and discussions
In order to understand the structure requirements for the glu-
cosamine derivatives to form stable and efficient hydro/organogels
at lower gelation concentrations, we synthesized and characterized
two new series of compounds, the amides 5 and ureas 6. These
compounds can be synthesized readily using the headgroup
glucosamine derivative 4, which was obtained in a few steps from
N-acetyl-glucosamine 7 as shown in Scheme 1.16 First, N-acetyl-
glucosamine 7 was methylated in the presence of acidic resin,
giving a mixture of anomers with the anomer as the major
D-
a
product. The resulting intermediate 8 was converted to the acetal 9
using benzylidene dimethyl acetal. The major isomer was separated
via recrystallization in ethanol, followed by hydrolysis using KOH to
afford the headgroup 4.
2.1. Preparation of amides and gelation properties
The amides 5 were prepared by the method shown in the last
step of Scheme 1. The amino group from 4 was typically function-
alized with an acid chloride in the presence of pyridine or trie-
thylamine to give the amide in good yield. The structures of the
OH
PhCH(OMe)2
OH
O
Ph
O
O
pTsOH
Amberlite IR120
MeOH
O
O
HO
HO
HO
HO
HO
NH
DMF
45°C, 2 hrs
90%
NH
OC
H3
NH
OCH3
O
OH
O
reflux, 6hrs
O
9
91% (a:β, 6:1)
8
7
O
X
O
Ph
O
+ base
O
R
HO
1) EtOH
NH
R
(70–89%)
recrystallization
O
O
O
OCH3
OCH3
Ph
5
O
O
2) 3N KOH, EtOH
reflux, 18 hrs
72% (2 steps)
HO
O
NH2
OCH3
Ph
O
NH
NH
R-NCO
O
4
HO
quantitative
6
R
Scheme 1. Synthesis of the amides and ureas from N-acetyl-D-glucosamine.

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N. Goyal et al. / Tetrahedron 66 (2010) 5962e5971
Table 1
Library of amide derivatives of 4 and their corresponding minimum gelation concentrations (MGCs) in mg/mL
R¼
Hexane
Water
EtOH
Water:DMSO (2:1)
Water:EtOH
(2:1)
THF
i-PrOH
DCM
10
11
12
13
14
I
I
G 5.0
G 4.0
G 1.3
G 1.0
G 1.2
G 10.0
4.0
S
S
S
S
S
S
S
S
S
S
S
C
C
I
S
G 1.3
G 2.0
G 1.6
G 5.0
S
G 1.7
S
S
P
C
I
S
S
I
G 10.0
G 20
15
16
17
18
19
20
21
C
I
S
G 5.0
G 2.0
G 1.7
C
G 2.2
G 0.7
G 1.2
G 10
G 2.5
G 5.0
G 20
S
C
P
S
P
S
S
G10
C
S
S
S
S
S
S
S
C
C
I
S
G 4.0
S
C
C
C
C
I
I
S
S
I
G 10
G 10
G 20
G 5
S
I
G 6.6
G 5
S
I
S
22
23
I
G 2
I
S
S
G 5.0
C
G 3.3
G 10
C
C
S
S
S
S
C
G, gel at room temperature; the numbers in the table are the minimum gelation concentrations in mg/mL; I, insoluble; C, crystallization; S, soluble at w20 mg/mL; P,
precipitation.
alkenyl derivatives, the pentenyl derivative 19 is a versatile gelator,
but the methacrylate derivative 18 is less efficient. The halogenated
compounds 20 and 21 also showed positive results. For the two aryl
derivatives, the phenyl amide 22 formed stable gels in water, and
aqueous DMSO and ethanol, while the naphthyl amide 23 only
formed gels in aqueous DMSO at higher concentrations.
For the sugar derivatives here, the urea analogs showed gelation
tendencies similar to the amides, with the aliphatic derivatives
with 5e7 carbons being most versatile gelators for aqueous
mixtures. Compounds 24e27 formed gels in EtOH/water and
DMSO/water at concentrations lower than 0.2 wt %. The presence of
a terminal acetylene group does not seem to affect gelation, and the
compounds with the same chain length as their saturated
counterparts gave similar gelation results. Interestingly, the chlor-
oethyl and methacryloylethyl ureas (30, 31) were also able to form
gels in aqueous solutions, while the carbamate and ester analogs
were not able to form gels in these solvents. The methacrylate 30
can form gels in water at 10 mg/mL. After hydrolysis of the
methacrylate, the alcohol 32 can also form stable clear gels in water
(Figure S1 in Supplementary data). Aromatic ureas are somewhat
less effective for aqueous solutions compared to the aliphatic ureas;
this may be due to the extra rigidity in the molecule. The aromatic
urea derivatives 33e35 contain hydrogen bonding functions plus
2.2. Preparation of ureas and gelation properties
Several urea derivatives were prepared by reacting compound 4
with a stoichiometric amount of the corresponding isocyanate in
THF. For the compounds with terminal acetylenes, terminal alkynyl
acids were converted to the corresponding isocyanates in situ by
Curtis rearrangement using DPPA and triethylamine. The reactions
generally proceeded with close to quantitative yields, and the
products can be purified on silica gel by flash chromatography
using a polar solvent. The structures of the ureas synthesized and
their gelation properties are shown in Table 2. The selection of the R
groups is based on the results from the carbamate and amide series
and the availability of starting materials. These include compounds
24e26, with saturated 5e7 carbon alkyl chains, and 27 and 28,
which are 5e6 carbon terminal alkynyl derivatives. The cyclohexyl
urea 29, several compounds with terminal substituents 30e32, and
aryl ureas 33e35 were also prepared. The gelation test results are
shown in Table 2. From the screening of the gelation results of these
compounds, we can determine how the structure of the alkyl or
aryl groups affects self-assembling.
the aromatic rings necessary for
p p stacking. These aromatic
ꢀ
interactions reinforce the molecular packing and result in stronger
intermolecular forces. Therefore, they tend to be insoluble or
crystallize in polar solvents.
We analyzed several gels in their gel states using optical
microscopy, in an attempt to reveal the supramolecular assembly of
the gels with the solvents still trapped inside. The dried xerogels
were also studied by optical microscopy and scanning electron
microscopy. These results are shown in Figures 2e5. The optical
micrographs of the wet gels formed by compounds 17 and 19 are

N. Goyal et al. / Tetrahedron 66 (2010) 5962e5971
5965
Table 2
Library of urea derivatives of 4 and corresponding MGCs (mg/mL)
R¼
Hexane
Water
EtOH
S
Water:DMSO (2:1)
G 1.2
Water:EtOH (2:1)
G 1.3
THF
S
i-PrOH
DCM
24
I
I
S
S
25
26
27
28
I
I
S
G 1.0
G 1.0
G 2.8
G 2.8
G 1.5
G 1.6
G 1.2
G 1.3
S
S
S
P
S
S
S
S
S
I
P
I
G 10
G 6.6
S
G20
G20
S
P
C
I
29
30
I
I
I
I
G 10
S
G 3.3
G 10
G 1.3
G 10
S
S
S
S
S
S
31
32
33
P
I
G 10
G 2.2
I
S
G 6.7
G 10
G 5
G 2.2
G 4.0
G 20
S
S
S
S
S
S
S
G 20
G 10
G20
S
I
34
35
I
I
I
I
I
G 2.5
G 2.2
G 2.0
P
C
S
S
S
S
S
G 15
G, stable gel at room temperature, the numbers are the minimum gelation concentrations in mg/mL; I, insoluble; C, crystallization; S, soluble at w20 mg/mL, P, precipitate.
shown in Figures 2 and 3. The gel of 17 in ethanol/water showed
bundled fibrous assemblies, as shown in Figure 2AeC. At lower
magnification (200ꢁ), we can see the long fibers floating in the gel
solvent matrix. Figure 2C is a picture of the bundled fibers in 2B at
a higher magnification, and it is evident that the dark regions are
composed of many tubular types of aggregates and smaller, softer,
feather like fibers spanning from the center. In DMSO/water solu-
tions, we also observed tubular types of structures, as shown in
Figure 2DeF. The fibers or tubules emerged from the gel media or
were trapped in the gel media (Fig. 2D and E). At higher magnifi-
cation (500ꢁ), we can observe the embedded fibrous network at
the surface of the gel droplet (Fig. 2F).
Figure 2. Optical micrographs of the gels formed by compound 17 in wet gel state. AeC are gels in EtOH/H2O (1:2) at 3 mg/mL; DeF are gels in DMSO/H2O (1:2) at 2 mg/mL. A, B, D,
and E are obtained at 200ꢁ magnification, C and F are at 500ꢁ magnification.

5966
N. Goyal et al. / Tetrahedron 66 (2010) 5962e5971
Figure 3. Optical micrographs of the gels formed by compound 19 in wet gel state. AeD are gels in EtOH/H2O (1:2) at 2.5 mg/mL; E and F are gels in DMSO/H2O (1:2) at 3 mg/mL.
These images were obtained under crossed polarizers in phase contrast mode. A and E are 200ꢁ, B, C, D, and F are at 500ꢁ magnification.
Figure 4. Optical micrographs of the gels formed by compounds 24 and 28 in gel phases. A, gel by 28 in EtOH/H2O (1:2) at 1.5 mg/mL; B, gel by 28 in DMSO/H2O (1:2) at 3.0 mg/mL;
C and D, gel by 24 in EtOH/H2O (1:2) at 1.5 mg/mL; E and F, gel by 24 in DMSO/H2O (1:2) at 1.2 mg/mL. Magnification for E is 200ꢁ, and for the rest is 500ꢁ.
The gels formed by compound 19 also showed somewhat sim-
ilar morphologies, as shown in Figure 3. In EtOH/H2O, we can
clearly observe the fibrous assemblies at low magnification
(Fig. 3A), while at higher magnification, more detailed features of
the fibrous networks can be observed (Fig. 3BeD), including bi-
refringent fibers and tubules. In DMSO/water, long fibers were also
the predominant morphologies observed in the gel (Fig. 3E and F).
These were more difficult to image since the gel is three-di-
mensional. In many regions, we were only able to focus on one slice
of the gels. Changing the focus on the microscope allowed us to
observe the gels at different depths and some of these images are
shown in Figure S2 in Supplementary data section.
We also obtained the optical micrographs of the ureas in the gel
phase, and these are shown in Figure 4. They formed somewhat
different morphologies compared tothose of the amides. Compound
28 formed a stable gel in ethanol/water (1:2). The gel surface was
smooth and contained some contiguous fibrous assemblies, though
it was difficult to obtain better-quality pictures since, typically,
they were not isolated fibers (Fig. 4A). In DMSO/water (1:2), it
formed a similar morphology, and a slice of the gel showed some
intertwined fibrous networks (Fig. 4B). The gel formed by com-
pound 24 showed different morphologies as well. In EtOH/H2O, in
thinner regions, we could observe the soft tubular networks
(Fig. 4C), while in the denser regions, when the solvent evapo-
rated, we were able to observe densely packed fibrous structures
(Fig. 4D). In DMSO/H2O, we again were able to see some contin-
uous intertwined fibrous assemblies at low magnification (Fig. 4E)
and the tubular fibrous networks were observed more clearly at
higher magnifications (Fig. 4F). Again, it was difficult to obtain the
images of the gels since they are -three-dimensional, so we
obtained the micrographs of different cross-sections of the gels.
These images showed that at different surfaces of the gels, similar
features of the fibrous assemblies can be observed (Figure S3 in
Supplementary data).

N. Goyal et al. / Tetrahedron 66 (2010) 5962e5971
5967
Figure 5. Optical micrographs (A, B, D, E) and scanning electron micrographs (C, F) of several dried gels. A, gel of compound 16 in EtOH/H2O (1:2) at 0.7 mg/mL, B and C, gel of
compound 12 in hexane at 1.7 mg/mL; D, gel formed by compound 11 in DMSO/H2O (1:2) at 1.0 mg/mL, E and F, gel formed by compound 32 in water at 2.5 mg/mL. Magnifications
for A, B, C, and E are1000ꢁ.
For the dried gels, it was easier to obtain their morphologies
using OM or EM, and several of these are shown in Figure 5. The
gels exhibit different morphologies, depending on their structures.
The optical microscopy of the dried gels revealed that flexible fibers
lead to more effective gelators, and that the derivatives with
straight alkyl chains (as opposed to aromatic groups) tend to form
these morphologies, especially in aqueous solvents. The gel formed
by 16 in ethanol/water showed long uniform fibrous features
(Fig. 5A). The gel of compound 11 in DMSO/water showed presence
of very thin fibrous network structures (Fig. 5D). Both the OM and
SEM of the gel formed by heptyl amide 12 in hexane showed the
formation of entangled fibrous networks (Fig. 5B and C). The urea
derivative 32 also formed fibrous or tubular type of structures
(Fig. 5E and F). The SEM indicated that the tubular structures
force in organogels. In aqueous solutions of DMSO and ethanol, the
presence of organic soluble components makes the hydrogen
bonding somewhat more important and the hydrophobic
interactions less important. The notable difference in the gelation
ability between the ester and carbamate derivatives of compound 4
indicates that the eNH is essential. This hydrogen bond donor is
likely involved in the formation of a one-dimensional hydrogen
bonding network. When the hydrogen bond donor NH group is
closer to the sugar pyranoside ring as in compounds 13 and 17, the
gelation capabilities are similar to that of the carbamates. Few of
the 2- or 3- monoesters of 4,6-O-benzylidene-methyl-a-D-gluco-
pyranoside (1) formed gels in water or in aqueous solution. From
esters to carbamates, amides, and ureas, the number of hydrogen
bond donors in the molecules increases. It seems that the increase
in intermolecular interactions is necessary to extend the network.
Typically, the amides and ureas formed more robust gels than the
esters. However, there is not much difference between the classes
of amides and ureas. We also carried out IR studies for two repre-
sentative compounds amide 17 and urea 24 in their solid and gel
states (in EtOH/H2O), respectively. The results are shown in Figures
S4 and S5 in the Supplementary data section. In the gel states, both
compounds exhibited similar patterns with their corresponding
solid forms except for the region from 2500 to 3500 cmꢀ1, at which
typically have diameters less than 1 mm.
From Tables 1 and 2, we can compare the gelation properties of
amides and ureas containing similar alkyl chain derivatives. The
compounds containing similar alkyl chain lengths are shown in
Table 3, where the headgroup linkages are ester 36, carbamate 37,
amide 12, or urea 24. The gelation ability of the compounds
increases with the addition of an NH hydrogen bond donor.
The solvents also affect the results, since hydrophobic forces are
dominant in hydrogels, whereas hydrogen bonding is the primary
Table 3
Comparing LMOGs with similar alkyl chain lengths. Positive gelation results are noted in mg/mL; P, precipitate; I, insoluble.
Compounds
36
37
12
24
H2O
I
20
I
I
H2O:DMSO 2:1
H2O:EtOH 2:1
P
P
3.0
1.4
1.0
2.0
1.2
1.3

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N. Goyal et al. / Tetrahedron 66 (2010) 5962e5971
the gels’ IR spectra showed broad and strong absorptions. This
clearly indicates the presence of hydrogen bonds of the gelator
molecules with the solvents.
4.2. General procedure for the synthesis of amides
4,6-O-Benzylidene-2-amino-2-deoxy-methyl-
-glucopyrano-
a-D
side 4 and pyridine or DIEA (2 equiv) were mixed in anhydrous THF
at 0 ꢂC. The corresponding acyl halide (1.1 equiv) was added
dropwise. After 4e6 h the reaction was diluted with DCM and
washed with H2O and then dilute HCl (w0.1 N). The organic layer
was dried with anhydrous Na2SO4. The crude products were puri-
fied using flash chromatography on silica gel with a solvent gra-
dient of hexane and acetone or DCM with 1–2% MeOH.
3. Conclusions
A series of amide and urea derivatives of the protected D-glu-
cosamine 4 were prepared and analyzed for their self-assembling
properties in several solvents. They were synthesized via straight-
forward reactions with high yields in general. We found that the
amides and ureas with alkyl chains are excellent gelators for so-
lutions of aqueous ethanol and aqueous DMSO, while the aryl de-
rivatives studied are also gelators for some polar solvents. In
comparison to the esters with similar acyl functional groups, the
amides and ureas showed enhanced gelation due to the presence of
extra hydrogen bond donors. Optical microscopy and scanning
electronic microscopy studies revealed that typically the aqueous
gels are composed of self-assembled fibrous networks. Therefore,
the glucosamine derivative 4 is a good building block for synthe-
sizing effective low molecular weight gelators, and the correlation
of the structure and gelation can be used for the design of other
functional organo/hydrogelators. These simple sugar-derived
LMWGs are expected to be useful in a variety of applications, such
as in entrapping large biomolecules including enzymes, and pro-
viding a good media for enzymatic reactions.
4.2.1. General procedure for the synthesis of ureas. The urea library
was synthesized by mixing compound 4 and the corresponding
isocyanate in stoichiometric quantities in anhydrous THF. The so-
lution was stirred at rt for 6e8 h. The crude products were purified
by flash chromatography on silica gel if the 1H NMR spectrum
indicates the product is not pure. Typically DCM/MeOH gradient
solvent system is used for the chromatographyseparation, if needed.
4.2.2. Pentyl amide 10. The compound was obtained as a white
solid at a yield of 88%, mp 195.2e196.0 ꢂC. 1H NMR (400 MHz,
CDCl3),
d (ppm) 7.47e7.54 (m, 2H), 7.32e7.40 (m, 3H), 5.83 (d, 1H,
J¼8.1 Hz), 5.57 (s, 1H), 4.72 (d, 1H, J¼4.0 Hz), 4.20e4.33 (m, 2H),
3.90 (dt, 1H, J¼3.3, 9.5 Hz), 3.78 (m, 2H), 3.59 (m, 1H), 3.41 (s, 3H),
3.13 (d, 1H, J¼3.3 Hz, OH), 2.26 (t, 2H, J¼7.3 Hz), 1.64 (m, 2H), 1.36
(sext, 2H, J¼7.3 Hz), 0.92 (t, 3H, J¼7.3 Hz). 13C NMR (100 MHz,
CDCl3)
d 174.7, 137.1, 129.1, 128.2, 126.3, 101.8, 98.8, 82.0, 70.7, 68.8,
62.3, 55.3, 54.0, 36.3, 27.6, 22.2, 13.7. HRMS calcd for C19H28NO6
4. Experimental section
4.1. General methods
[MþH]þ 366.1917, found 366.1920.
4.2.3. Hexyl amide 11. The hexyl amidewas obtained as awhite solid
at a yield of 86%, mp 192.3e193.1 ꢂC. 1H NMR, (400 MHz, CDCl3)
4.1.1. Gelation testing. The compounds were tested in a 1 dram vial
with a rubber lined screw cap from Kimble. A starting concentra-
tion of 20 mg/mL was used. The mixture was heated and sonicated
until the sample was fully dissolved. Typically the mixture was
heated in a closed container at lower temperature than the boiling
points of the solvents used. The solution was then left at room
temperature for 20e30 min. The vial was then examined by visual
observation; if it appears as a homogenous liquid/solid, the vial is
inverted, and if no solvent flows while the gel is inverted or gently
shaking then it is called a stable gel. If the semi-solid like material
falls apart during inversion and by gentle shaking, then it is called
an unstable gel or self-supporting solids depending on the ap-
pearance. If a stable gel is formed, serial dilution is performed until
the resulting gel is no longer stable. The concentration prior to
formation of the unstable gel was recorded as the minimum gela-
tion concentration (MGC).
d
(ppm) 7.47e7.52 (m, 2H), 7.33e7.39 (m, 3H), 5.85 (d, 1H, J¼8.4 Hz),
5.57 (s, 1H), 4.72 (d, 1H, J¼3.7 Hz), 4.19e4.32 (m, 2H), 3.91 (ddet, 1H,
J¼9.7 Hz), 3.74e3.83 (m, 2H), 3.59 (m, 1H), 3.41 (s, 3H), 2.25 (t, 2H,
J¼7.3), 1.65 (p, 2H, J¼7.3 Hz), 1.32 (m, 4H), 0.90 (t, 3H, J¼7.2 Hz). 13C
NMR, (100 MHz, CDCl3) d (ppm) 174.9,137.0,129.1,128.2,126.2,101.8,
98.9, 82.0, 69.7, 68.7, 62.4, 55.2, 53.8, 36.3, 31.2, 25.1, 22.2,13.8. HRMS
calcd for C20H30NO6 [MþH]þ 380.2073, found 380.2071.
4.2.4. Heptyl amide 12. The product was obtained as a white crys-
talline solid at a yield of 87%, mp 197.8e198.1 ꢂC. 1H NMR (400 MHz,
CDCl3)
d (ppm) 7.44e7.51 (m, 2H), 7.30e7.38 (m, 3H) 6.08 (d, 1H,
J¼8.8 Hz), 5.54 (s,1H), 4.69 (d,1H, J¼3.7 Hz), 4.25 (m,1H), 4.15 (d,1H,
J¼3.7, 9.9 Hz), 3.83 (t, 1H, J¼9.7 Hz), 3.69e3.78 (m, 2H), 3.55 (m, 1H),
3.37 (s, 3H), 2.13e2.26 (m, 3H), 1.60 (m, 2H), 1.27 (s, 6H), 0.85 (t, 3H,
J¼6.6 Hz).13C NMR (100 MHz, CDCl3)
d 174.8, 137.0, 129.1, 128.2, 126.2,
101.9, 98.9, 82.1, 70.0, 68.8, 62.4, 55.3, 53.8, 36.5, 31.4, 28.7, 25.5, 22.4,
14.0. HRMS calcd for C21H32NO6 [MþH]þ 394.2230, found 394.2237.
4.1.2. Optical microscopy. The slides were prepared after a stable
gel was formed. A small amount of the gel was placed on a clean
glass slide and observed immediately while the solvent is still
present. For DMSO aqueous solutions, since the solvent evaporates
very slowly, the gels were observed within 2 h typically. For the
dried gels, the slides were air dried for hydrogels and in a desiccator
for organogels for overnight or longer. The gels were observed with
an Olympus BX60M optical microscope using a DSP Color Hi-Res
EXvision camera and an Olympus U-TV1X lens. The program used
to acquire and store the photos was Corel Photo-Paint 7.
4.2.5. Octyl amide 13. The product was obtained as a white crys-
talline solid at a yield of 88%, mp 183.8e185.0 ꢂC. 1H NMR
(400 MHz, CDCl3)
d (ppm) 7.46e7.52 (m, 2H), 7.33e7.39 (m, 3H),
5.85 (d, 1H, J¼8.8 Hz), 5.57 (s, 1H), 4.72 (d, 1H, J¼4.0 Hz), 4.28 (m,
1H), 4.23 (m, 1H), 3.90 (t, 1H, J¼9.5 Hz), 3.74e3.83 (m, 2H), 3.59 (m,
1H), 3.41 (s, 3H), 3.15 (br s, 1H), 2.25 (m, 2H), 1.64 (m, 2H), 1.19e1.40
(m, 8H), 0.87 (t, 3H, J¼7.0 Hz). 13C NMR (100 MHz, CDCl3)
d (ppm)
174.7, 137.0, 129.2, 128.2, 126.3, 101.9, 98.8, 82.1, 70.9, 68.8, 62.3,
55.3, 54.0, 36.6, 31.7, 29.1, 29.0, 25.6, 22.6, 14.0. HRMS calcd for
C22H34NO6 [MþH]þ 408.2386, found 408.2395.
4.1.3. Scanning electron microscopy. Samples were prepared by
drying the gel on an aluminum pellet in a desiccator under reduced
pressure for several days. A thin layer of platinum was deposited on
to the pellet by a Denton Vacuum (model Desk II) at a reduced
pressure of w30 mtorr and a current of 45 mA for 60 s. The sample
was analyzed using a JEOL JSM 5410 scanning microscope.
4.2.6. 4-Pentynyl amide 14. The compound was obtained as a white
solid at a yield of 79%, mp 180.0e180.7 ꢂC. 1H NMR (400 MHz,
CDCl3),
d (ppm) 7.46e7.53 (m, 2H), 7.32e7.40 (m, 3H), 6.04 (d, 1H,
J¼8.4 Hz), 5.57(s,1H), 4.72 (d,1H, J¼4.0 Hz), 4.22e4.33 (m, 2H), 3.91
(t, 1H, J¼9.5 Hz), 3.73e3.85 (m, 2H), 3.59 (m, 1H), 3.41 (s, 3H), 2.99

N. Goyal et al. / Tetrahedron 66 (2010) 5962e5971
5969
(br s, 1H), 2.52e2.59 (m, 2H), 2.45e2.50 (m, 2H), 2.02 (m, 1H). 13
C
2.14 (m, 2H). 13C NMR (100 MHz, CDCl3)
d
173.1, 136.9, 129.0, 128.1,
NMR (100 MHz, CDCl3)
d
172.4, 136.9, 129.1, 128.1, 126.2, 101.8, 98.8,
126.1, 101.7, 98.8, 81.8, 69.3, 68.7, 62.4, 55.2, 53.8, 44.2, 33.0, 27.9.
82.6, 81.9, 69.5, 69.2, 68.7, 62.4, 55.2, 53.9, 35.0, 14.7. HRMS calcd for
HRMS calcd for C18H25NO6Cl [MþH]þ 386.1370, found 386.1355.
C19H24NO6 [MþH]þ 362.1604, found 366.1604.
4.2.13. 5-Bromopenyl amide 21. The compound was obtained as
a white solid at a yield of 80.5%, mp 169.2e170.0 ꢂC. 1H NMR
4.2.7. 5-Hexynyl amide 15. Flash chromatography (CH2Cl2:MeOH
9.3:0.7) was used to obtain the product in 70% yield as a white solid,
(400 MHz, CDCl3), d (ppm) 7.45e7.52 (m, 2H), 7.33e7.39 (m, 3H), 5.88
mp 176.1e177.0 ꢂC. 1H NMR (400 MHz, CDCl3),
d
(ppm) 7.47e7.52
(d,1H, J¼8.4 Hz), 5.56 (s,1H), 4.72 (d,1H, J¼4.0 Hz), 4.28 (m,1H), 4.22
(m,1H), 3.89 (ddet,1H, J¼9.7 Hz), 3.77 (m, 2H), 3.58 (m,1H), 3.41 (t, 2H,
J¼6.6 Hz), 3.40 (s, 3H), 2.38 (t, 2H, J¼7.1 Hz),1.90 (m, 2H),1.81 (m, 2H).
(m, 2H), 7.33e7.40 (m, 3H), 5.92 (d, 1H, J¼8.8 Hz), 5.57 (s, 1H), 4.72
(d, 1H, J¼3.7 Hz), 4.20e4.31 (m, 2H), 3.90 (dt, 1H, J¼3.3, 9.9 Hz),
3.73e3.83 (m, 2H), 3.59 (m, 1H), 3.41 (s, 3H), 3.06 (d, 1H, J¼3.3 Hz),
2.41 (t, 2H, J¼7.1 Hz), 2.28 (m, 2H), 1.99 (t, 1H, J¼2.6 Hz), 1.88 (m,
13C NMR (100 MHz, CDCl3)
d 173.1,136.9,129.0,128.1,126.1,101.7, 98.8,
81.8, 69.2, 68.6, 62.4, 55.1, 53.8, 44.2, 32.9, 27.9. HRMS calcd for
2H). 13C NMR (100 MHz, CDCl3)
d
172.7, 137.0, 129.2, 128.3, 126.3,
C19H27BrNO6 [MþH]þ 444.1022, found 444.1014.
101.9, 98.8, 83.4, 82.0, 70.8, 69.3, 68.8, 62.3, 55.3, 53.9, 34.9, 23.9,
17.6. HRMS calcd for C20H26NO6 [MþH]þ 376.1760, found 376.1756.
4.2.14. Benzoyl amide 2243. The product was obtained as a white
crystalline solid at a yield of 89%, mp 247.2e247.8 1H NMR
4.2.8. 6-Heptynyl amide 16. The compound was isolated as a white
(400 MHz, CDCl3/MeOH),
d
(ppm) 7.74 (d, 2H, J¼8.1 Hz), 7.40e7.47
solid, 70%, mp 174.4e175.1 ꢂC. 1H NMR (400 MHz, CDCl3),
d
(ppm)
(m, 3H), 7.33e7.38 (m, 3H), 7.26e7.32 (m, 3H), 5.52 (s, 1H), 4.78 (d,
1H. J¼3.7 Hz), 4.27 (dd, 1H, J¼3.3, 10.3 Hz), 4.22 (m, 1H), 3.91 (t, 1H,
J¼9.5 Hz), 3.70e3.82 (m, 2H), 3.57 (t, 1H, J¼8.8 Hz), 3.33 (s, 3H). 13C
7.47e7.53 (m, 2H), 7.33e7.40 (m, 3H), 5.85 (d, 1H, J¼8.4 Hz), 5.57 (s,
1H), 4.72 (d, 1H, J¼3.7 Hz), 4.29 (m, 1H), 4.24 (ddd, 1H, J¼3.7, 4.0,
8.8 Hz), 3.90 (dt, 1H, J¼3.3, 9.5 Hz), 3.74e3.85 (m, 2H), 3.59 (m, 1H),
3.41 (s, 3H), 3.03 (d, 1H, J¼3.3 Hz), 2.29 (t, 2H, J¼7.3 Hz), 2.22 (dt,
1H, J¼2.6, 7.0 Hz), 1.96 (t, 1H, J¼2.6 Hz), 1.79 (m, 2H), 1.58 (m, 2H).
NMR (100 MHz, CDCl3/MeOH)
d (ppm) 168.7, 137.0, 133.6, 131.8,
129.0, 128.4, 128.1, 127.0, 126.1, 102.1, 99.1, 81.9, 69.1, 68.7, 62.5, 55.2,
54.4. HRMS calcd for C21H24NO6 [MþH]þ 386.1604, found 386.1595.
13C NMR (100 MHz, CDCl3)
d 174.0, 137.0, 129.1, 128.2, 126.3, 101.8,
98.8, 84.0, 82.0, 70.6, 68.8, 68.6, 62.3, 55.3, 53.9, 35.9, 27.7, 24.6, 18.1.
4.2.15. Naphthyl amide 23. The compound was obtained as a white
solid at a yield of 84%, mp 206.8e207.4 ꢂC. 1H NMR (400 MHz,
HRMS calcd for C21H28NO6 [MþH]þ 390.1917, found 390.1917.
CDCl3, CD3OD),
d
(ppm) 8.34 (d, 1H, J¼8.1 Hz), 7.93 (d, 1H, J¼8.4 Hz),
4.2.9. 10-Undecynyl amide 17. The product was obtained as a white
solid at a yield of 84%, mp 184.5e185.3 ꢂC. 1H NMR (400 MHz,
7.88 (d, 1H, J¼7.3 Hz), 7.67 (d, 1H, J¼7.0 Hz), 7.43e7.59 (m, 5H),
7.32e7.40 (m, 3H), 6.38 (d, 1H, J¼8.8 Hz), 5.60 (s, 1H), 4.93 (d, 1H,
J¼3.7 Hz), 4.53 (m, 1H), 4.31 (m, 1H), 4.02 (m, 1H), 3.75e3.88 (m,
2H), 3.63 (t, 1H, J¼9.2 Hz), 3.41 (s, 3H), 3.25 (d, 1H, J¼3.3 Hz). 13C
CDCl3)
d (ppm) 7.46e7.52 (m, 2H), 7.32e7.39 (m, 3H), 5.92 (d, 1H,
J¼8.4 Hz), 5.54 (s, 1H), 4.71 (d, 1H, J¼3.7 Hz), 4.26 (m, 1H), 4.20
(ddd, 1H, J¼3.7, 4.0, 8.8 Hz), 3.87 (t, 1H, J¼9.6 Hz), 3.71e3.82 (m,
2H), 3.57 (t, 1H, J¼9.0 Hz), 3.38 (s, 3H), 2.22 (m, 2H), 2.16 (dt, 2H,
J¼2.6, 7.1 Hz), 1.93 (t, 1H, J¼2.6 Hz), 1.62 (m, 2H), 1.50 (pentet, 2H,
NMR (100 MHz, CDCl3, CD3OD)
d 170.7, (170.6 minor rotamer),
136.9, 133.6 (133.62, minor rotamer), 133.4, 130.6, 129.8, 129.0,
128.1, 128.06, 127.0, 126.2, 126.1, 125.1, 124.9, 124.6, 101.7, 98.9, 81.9,
69.1, 68.7, 62.5, 55.2, 54.4 (54.5, minor tautomer). HRMS calcd for
C25H26NO6 [MþH]þ 436.1760, found 436.1742.
J¼7.0),1.37 (m, 2H),1.29 (m, 6H). 13C NMR (100 MHz, CDCl3)
d (ppm)
174.6,137.1,129.1, 128.2, 126.3, 101.8, 98.8, 84.6, 82.0, 70.5, 68.7, 68.1,
62.3, 55.2, 53.9, 36.5, 29.1, 29.0, 28.8, 28.5, 28.3, 25.5, 18.3. HRMS
calcd for C25H36NO6 [MþH]þ 446.2543, found 446.2524.
4.2.16. Pentyl urea 24. The compound was obtained as a white solid
at a yield of 96%, mp 186.2e187.0. 1H NMR (400 MHz, DMSO-d6)
4.2.10. Methacrylamide 18. The compound was obtained as a white
solid at a yield of 85%, mp 187.2e187.9 ꢂC. 1H NMR (400 MHz,
d
(ppm) 7.41e7.49 (m, 2H), 7.34e7.41 (m, 3H), 6.06 (t, 1H, J¼5.5 Hz),
5.79 (d, 1H, J¼8.8 Hz), 5.59 (s, 1H), 5.21 (d, 1H. J¼5.1 Hz), 4.61 (d, 1H,
J¼3.7 Hz), 4.16 (dd, 1H, J¼4.8, 9.9 Hz), 3.63e3.77 (m, 2H), 3.41e3.62
(m, 3H), 3.28 (s, 3H), 2.95 (q, 2H, J¼6.3 Hz), 1.35 (pentet, 2H,
J¼7.0 Hz), 1.24 (m, 4H), 0.85 (t, 3H, J¼6.6 Hz). 13C NMR, (100 MHz,
CDCl3),
d (ppm) 7.45e7.55 (m, 2H), 7.30e7.42 (m, 3H), 6.21 (d, 1H,
J¼8.4 Hz), 5.76 (s, 1H), 5.56 (s, 1H), 5.39 (s, 1H), 4.76 (d, 1H,
J¼3.7 Hz), 4.23e4.33 (m, 2H), 3.94 (t, 1H, J¼9.5 Hz), 3.72e3.84 (m,
2H), 3.60 (t, 1H, J¼8.8 Hz), 3.40 (s, 3H), 3.29 (s, 1H), 1.99 (s, 3H). 13C
DMSO-d6)
d (ppm) 158.1, 137.8, 129.0, 128.1, 126.5, 101.0, 99.6, 82.0,
NMR (100 MHz, CDCl3)
d
169.3, 139.2, 137.1, 129.1, 128.2, 126.3,
68.6, 68.1, 62.6, 54.8, 54.7, 39.2, 29.6, 28.7, 21.9, 14.0. HRMS calcd for
120.7, 101.8, 98.8, 82.0, 70.6, 68.8, 62.3, 55.3, 54.1, 18.5. HRMS calcd
C20H31N2O6 [MþH]þ 395.2182, found 395.2196.
for C18H24NO6 [MþH]þ 350.1604, found 355.1588.
4.2.17. Hexyl urea 25. Isolated as a light yellow solid in quantitative
4.2.11. 5-Hexenyl amide 19. The compound was obtained as a white
solid at a yield of 76%, mp 178.1e179.0 ꢂC. 1H NMR (400 MHz, CDCl3),
yield, mp 183.8e185.0 ꢂC. 1H NMR (400 MHz, DMSO-d6)
d (ppm)
7.42e7.49 (m, 2H), 7.34e7.41 (m, 3H), 6.07 (t, 1H, J¼5.5 Hz), 5.80 (d,
1H, J¼8.4 Hz), 5.60 (s, 1H), 5.22 (br s, 1H), 4.62 (d, 1H, J¼3.7 Hz), 4.17
(dd, 1H, J¼4.8, 9.9 Hz), 3.73 (t, 1H, J¼10.3 Hz), 3.69 (dd, 1H, J¼3.7,
8.8 Hz), 3.55e3.62 (m, 1H), 3.49 (m, 2H), 3.30 (s, 3H), 2.98 (q, 2H,
J¼6.2 Hz), 1.35 (m, 2H),1.25 (br s, 6H), 0.86 (t, 3H, J¼6.8 Hz). 13C NMR
d
(ppm) 7.46e7.52 (m, 2H), 7.33e7.39 (m, 3H), 5.86 (d, 1H, J¼8.4 Hz),
5.77 (m, 1H), 5.56 (s, 1H), 5.03 (d, 1H, J¼17.9 Hz), 4.99 (d, 1H,
J¼10.6 Hz), 4.71 (d, 1H, J¼3.7 Hz), 4.28e4.19 (m, 2H), 3.88 (t, 1H,
J¼9.5 Hz), 3.77(m, 2H), 3.58(m,1H), 3.40(s, 3H),3.19(brs,1H), 2.25(t,
2H, J¼7.5 Hz), 2.10 (q, 2H, J¼7.0 Hz), 1.76 (pentet, 2H, J¼7.5 Hz). 13C
(100 MHz, DMSO-d6)
d (ppm) 157.9, 137.7, 128.8, 127.9, 126.3, 100.8,
NMR (100 MHz, CDCl3)
d
174.3, 137.8, 137.1, 129.2, 128.2, 126.3, 115.5,
99.5, 81.9, 68.5, 68.0, 62.4, 54.6, 54.55, 39.1, 31.0, 29.8, 26.0, 22.0,13.8.
101.9, 98.8, 82.0, 70.8, 68.8, 62.3, 55.3, 54.0, 35.7, 33.0, 24.5. HRMS
HRMS calcd for C21H33N2O6 [MþH]þ 409.2339, found 409.2355.
calcd for C20H28NO6 [MþH]þ 378.1917, found 378.1899.
4.2.18. Heptyl urea 26. Isolated as an off white solid in quantitative
4.2.12. 4-Chlorobutyl amide 20. The compound was obtained as
a white solid at a yield of 89%, mp 195.2e196.1. ꢂC. 1H NMR
yield, mp 201.3e202.2 ꢂC. 1H NMR (400 MHz, DMSO)
d (ppm)
7.40e7.46 (m, 2H), 7.32e7.39 (m, 3H), 6.04 (t, 1H, J¼5.5 Hz), 5.78 (d,
1H, J¼8.4 Hz), 5.58 (s, 1H), 5.21 (d, 1H, J¼5.1 Hz), 4.60 (d, 1H,
J¼3.2 Hz), 4.15 (dd, 1H, J¼4.6, 9.8 Hz), 3.63e3.74 (m, 2H), 3.57 (m,
1H), 3.42e3.51 (m, 2H), 3.28 (s, 3H), 2.96 (q, 2H, J¼6.2 Hz), 1.33 (m,
2H), 1.23 (br s, 8H), 0.84 (t, 3H, J¼6.4 Hz). 13C NMR (100 MHz,
(400 MHz, CDCl3),
d (ppm) 7.46e7.53 (m, 2H), 7.34e7.40 (m, 3H),
5.89 (d, 1H, J¼8.4 Hz), 5.57 (s, 1H), 4.72 (d, 1H, J¼4.0 Hz), 4.21e4.34
(m, 2H), 3.91 (dt, 1H, J¼2.9, 9.9 Hz), 3.73e3.84 (m, 2H), 3.55e3.68
(m, 3H), 3.42 (s, 3H), 2.91 (d, 1H, J¼2.9 Hz), 2.46 (t, 2H, J¼7.0 Hz),

5970
N. Goyal et al. / Tetrahedron 66 (2010) 5962e5971
DMSO)
d
157.8, 137.7, 128.8, 127.9, 126.3, 100.8, 99.4, 81.9, 68.4, 68.0,
2H, overlap), 3.29 (s, 3H), 3.05 (q, 2H, J¼5.5 Hz). 13C NMR (100 MHz,
62.4, 54.6, 54.5, 39.1, 31.2, 29.9, 28.4, 26.3, 22.0, 13.9. HRMS calcd for
DMSO-d6) d (ppm) 158.2, 137.7, 128.8, 128.0, 126.4, 100.8, 99.5, 81.9,
C22H35N2O6 [MþH]þ 423.2495, found 423.2500.
68.3, 68.0, 62.5, 60.7, 54.7, 42.0. HRMS calcd for C17H25N2O7
[MþH]þ 369.1662, found 369.1677.
4.2.19. 4-Pentynyl urea 27. The compound was obtained as a white
solid at a yield of 90.5%, mp 210.0e211.0 ꢂC. 1H NMR (400 MHz,
DMSO),
4.2.25. Phenyl urea 33. Isolated as a light yellow solid in quanti-
d
(ppm) 7.42e7.48 (m, 2H), 7.34e7.41 (m, 3H), 6.13 (t, 1H,
tative yield, mp >300 ꢂC. 1H NMR (400 MHz, DMSO-d6)
d (ppm)
J¼5.6 Hz), 5.78 (d, 1H, J¼8.8 Hz), 5.60 (s, 1H), 5.20 (d, 1H, J¼5.5 Hz),
4.62 (d, 1H, J¼3.7 Hz), 4.17 (dd, 1H, J¼4.8, 9.9 Hz), 3.73 (m, 1H), 3.69
(m, 1H), 3.59 (dt, 1H, J¼4.8, 9.9 Hz), 3.44e3.55 (m, 2H), 3.30 (s, 3H),
3.04 (pseudo q, 2H, J¼6.0 Hz), 2.78 (t, 1H, J¼2.6 Hz), 2.15 (dt, 2H,
J¼2.6, 7.0 Hz), 1.54 (pentet, 2H, J¼7.0 Hz), 13C NMR (100 MHz,
8.65 (s, 1H), 7.43e7.49 (m, 2H), 7.43e7.42 (m, 5H), 7.22 (m, 2H), 6.89
(m, 1H), 6.15 (d, 1H, J¼8.8 Hz), 5.63 (s, 1H), 5.34 (br s, 1H), 4.71 (d,
1H, J¼3.3 Hz), 4.20 (dd, 1H, J¼4.8, 9.9 Hz), 3.72e3.83 (m, 2H), 3.63
(m, 1H), 3.49e3.60 (m, 2H), 3.34 (s, 3H). 13C NMR (100 MHz, DMSO-
d6) d (ppm) 154.8, 140.3, 137.7, 128.8, 128.6, 127.9, 126.3, 121.0, 117.3,
DMSO)
d
157.8, 137.7, 128.8, 127.9, 126.3, 100.8, 99.4, 83.9, 82.0, 71.3,
100.8, 99.2, 81.7, 68.3, 68.0, 62.6, 54.7, 54.2. HRMS calcd for
68.5, 68.0, 62.4, 55.6, 54.5, 38.2, 28.8, 15.2. HRMS calcd for
C21H25N2O6 [MþH]þ 401.1713, found 401.1726.
C20H27N2O6 [MþH]þ 391.1869, found 391.1855.
4.2.26. 4-Bromophenyl urea 34. The compound was obtained as
4.2.20. 5-Hexynyl urea 28. The compound was obtained as a white
solid at a yield of 87%, mp 212.0e213.0 ꢂC. 1H NMR (400 MHz,
a white solid at a yield of 92%, mp unstable after 265 ꢂC. 1H NMR,
(400 MHz, DMSO-d6)
d (ppm) 8.77 (br s, 1H), 7.43e7.48 (m, 2H),
CDCl3),
d
(ppm) 7.47e7.52 (m, 2H), 7.33e7.39 (m, 3H), 5.58 (s, 1H),
7.33e7.42 (m, 7H), 6.16 (d, 1H, J¼8.4 Hz), 5.62 (s, 1H), 5.33 (d, 1H,
J¼5.5 Hz), 4.70 (d, 1H, J¼3.7 Hz), 4.19 (dd, 1H, J¼4.8, 9.9 Hz),
3.72e3.82 (m, 2H), 3.49e3.66 (m, 3H), 3.33 (s, 3H). 13C NMR
4.72 (d, 1H, J¼3.7 Hz), 4.62e4.81 (m, 2H), 4.28 (m, 1H), 3.84e3.96
(m, 2H), 3.73e3.83 (m, 2H), 2.53e3.61 (m, 1H), 3.40 (s, 3H), 3.21 (m,
2H), 2.22 (dt, 2H, J¼2.6, 6.9 Hz), 1.96 (t, 1H, J¼2.6 Hz), 1.51e1.68 (m,
(100 MHz, DMSO-d6) d (ppm) 154.6, 139.7, 137.7, 131.4, 128.8, 128.0,
4H). 13C NMR (100 MHz, CDCl3eone drop of CD3OD)
d
159.2, 137.0,
126.4, 1119.3, 112.3, 100.8, 99.2, 81.7, 68.3, 68.0, 62.6, 54.7, 54.2.
129.0, 128.1, 126.2, 101.8, 99.5, 84.1, 82.0, 70.5, 68.8, 68.5, 62.4, 55.2,
54.9, 39.5, 28.9, 25.5, 18.0. HRMS calcd for C21H29N2O6 [MþH]þ
405.2026, found 405.2034.
HRMS calcd for C21H24N2O6Br [MþH]þ 479.0818, found 479.0836.
4.2.27. Napthyl urea 35. Isolated as a light yellow solid in quanti-
tative yield, mp 253.8e255.0 ꢂC. 1H NMR, (400 MHz, DMSO-d6)
4.2.21. Cyclohexyl urea 29. Isolated as a light yellow solid in quan-
d
(ppm) 8.73 (s, 1H), 8.14 (d, 1H, J¼8.1 Hz), 8.09 (d, 1H, J¼7.7 Hz),
titative yield, mp 210 ꢂC (dec). 1H NMR (400 MHz, DMSO-d6)
d
(ppm)
7.87 (d, 1H, J¼8.1 Hz), 7.49e7.56 (m, 3H), 7.44e7.49 (m, 2H),
7.39e7.43 (m, 1H), 7.34e7.39 (m, 3H), 6.81 (d, 1H, J¼8.4 Hz), 5.63 (s,
1H), 5.42 (br s, 1H), 4.76 (d, 1H, J¼3.3 Hz), 4.20 (dd, 1H, J¼4.4,
9.9 Hz), 3.88 (m,1H), 3.77 (t,1H, J¼10.1 Hz), 3.60e3.71 (m, 2H), 3.56
7.42e7.47 (m, 2H), 7.35e7.40 (m, 3H), 6.04 (d, 1H, J¼8.1 Hz), 5.74 (d,
1H, J¼8.4 Hz),5.60(s,1H), 5.23(d,1H, J¼4.8 Hz), 4.61(d,1H, J¼3.3 Hz),
4.17 (dd,1H, J¼4.8,9.9 Hz), 3.64e3.76 (m, 2H), 3.58(m,1H), 3.44e3.54
(m, 2H), 3.36 (m, 1H), 3.34 (s, 3H), 1.68e1.78 (m, 2H), 1.57e1.67 (m,
2H),1.46e1.55 (m,1H),1.19e1.32 (m, 2H),1.00e1.18 (m, 3H).13C NMR
(m, 1H), 3.36 (s, 3H). 13C NMR, (100 MHz, DMSO-d6)
d 155.4, 137.7,
135.1, 133.7, 128.9, 128.4, 128.1, 126.4, 126.0, 125.8, 125.4, 125.0,
121.9, 121.2, 115.7, 101.0, 99.4, 81.9, 68.5, 68.1, 62.7, 54.8, 54.5. HRMS
calcd for C25H27N2O6 [MþH]þ 451.1869, found 451.1882.
(100 MHz, DMSO-d6)
d (ppm) 157.1, 137.7, 128.8, 127.9, 126.3, 100.8,
99.4, 81.9, 68.5, 68.0, 62.4, 54.6, 54.5, 47.6, 33.2, 25.2, 24.3. HRMS calcd
for C21H31N2O6 [MþH]þ 407.2182, found 407.2191.
Acknowledgements
4.2.22. 2-Chloroethyl urea 30. The compound was obtained as
a white solid at a yield of 95%, mp 184.1 ꢂC. 1H NMR, (400 MHz,
We thank the financial support from National Science Founda-
tion (grant CHE-518283). We also thank PVN Reddy, Hao Yang, and
Kristopher Williams for their assistance during the preparation of
the manuscript.
DMSO-d6) d (ppm) 7.40e7.47 (m, 2H), 7.33e7.39 (m, 3H), 6.34 (t,1H,
J¼5.5 Hz), 6.07 (d, 1H, J¼8.8 Hz), 5.58 (s, 1H), 5.20 (d, 1H, J¼5.5 Hz),
4.61 (d, 1H, J¼3.3 Hz), 4.15 (dd, 1H, J¼4.8, 9.9 Hz), 3.64e3.75 (m,
2H), 3.53e3.61 (m, 3H), 3.42e3.53 (m, 2H), 3.32 (m, 2H), 3.28 (s,
3H). 13C NMR, (100 MHz, DMSO-d6)
d (ppm) 157.6, 137.7, 128.9,
Supplementary data
128.0, 126.4, 100.8, 99.4, 81.9, 68.3, 68.0, 62.5, 54.7, 54.6, 44.7, 41.4.
HRMS calcd for C17H24N2O6Cl [MþH]þ 387.1323, found 387.1335.
The 1H and 13C NMR spectra for compounds 10e35 are provided
in supplementary data file. The preparation of compound 4 is also
provided in the Supplementary data. The photographs of gels
formed by 12 and 32, and optical micrographs of gels by com-
pounds 19 and 24 are also shown in the Supplementary data sec-
tion. Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.tet.2010.05.071. These data
include MOL files and InChIKeys of the most important compounds
described in this article.
4.2.23. 2-Methyl-acrylic acid 2-ureido-ethyl ester 31. The com-
pound was obtained as a white solid in quantitative yield, mp
198.8e200.0 ꢂC. 1H NMR (400 MHz, DMSO-d6)
d (ppm) 7.42e7.48
(m, 2H), 7.34e7.40 (m, 3H), 6.24 (t, 1H, J¼5.7 Hz), 6.08 (br s, 1H),
5.99 (d, 1H, J¼8.4 Hz), 5.70 (m, 1H), 5.60 (s, 1H), 5.20 (d, 1H,
J¼5.5 Hz), 4.62 (d, 1H, J¼3.7 Hz), 4.17 (dd, 1H, J¼4.8, 9.9 Hz), 4.06
(m, 2H), 3.66e3.77 (m, 2H), 3.65e3.63 (m, 1H), 3.43e3.53 (m, 2H),
3.22e3.32 (m, 5H), 1.89 (s, 3H). 13C NMR (100 MHz, DMSO-d6)
d
(ppm) 166.5, 157.7, 137.7, 135.8, 128.8, 127.9, 126.4, 125.9, 100.8,
References and notes
99.4, 81.9, 68.3, 68.0, 64.2, 62.5, 54.62, 54.57, 38.1, 17.9. HRMS calcd
for C21H29N2O8 [MþH]þ 437.1924, found 437.1944.
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