Protecting group/halogen effect of N-glycosylamines on the self assembly of organogelator

Article abstract of DOI:10.1039/b9nj00400a

A series of N-glycosylamine based organogelators were synthesised from three different 4,6-O-protected saccharides. All these compounds were characterized using different spectral techniques. The effect of substituents present in the N-glycosylamines on g

Full text of DOI:10.1039/b9nj00400a

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Protecting group/halogen effect of N-glycosylamines on the self assembly
of organogelator
Subbiah Nagarajan,a Pawar Ravinder,b Venkatesan Subramanianb and
Thangamuthu Mohan Das*a
Received (in Gainesville, FL, USA) 12th August 2009, Accepted 29th September 2009
First published as an Advance Article on the web 5th November 2009
DOI: 10.1039/b9nj00400a
A series of N-glycosylamine based organogelators were synthesised from three different
4,6-O-protected saccharides. All these compounds were characterized using different spectral
techniques. The effect of substituents present in the N-glycosylamines on gelation was studied
from NMR and computation. Among the eighteen different gelators studied, 3b, bearing fluorine
as a substituent, was observed to gelate at very low concentrations (CGC: 1%). Further,
it is revealed that dipole–dipole interactions play an important role in the case of
N-glycosylamine-based gelators. The presence of p–p stacking and H-bonding, as
inferred from the reported X-ray diffraction data, are responsible for the gelation. Various
possible modes of interaction are identified from computational studies. The gelation properties
of these compounds were studied with regard to their molecular structure by scanning electron
microscopy, differential scanning calorimetry, FT-IR and NMR studies.
(BzGP) 2c were synthesised from D-glucose (1)6–9 and
Introduction
characterised by adopting literature procedures. N-Glycosyl-
In recent years, low molecular weight organogelators
amines were synthesised by reacting the primary amine in the
(LMOGs) have played an important role in the field of
aromatic moiety and the active hydroxyl group of the
materials.1 Some of the sugar-based derivatives possessing
4,6-O-protected D-glucose.10–12 N-Glycosylamine compounds
strong H-bond-forming segments are prone to form gels even
at low concentration.2 Molecular self assembly is becoming a
(3–5) were identified through spectral techniques. During the
synthesis of different N-glycosylamines using partially-
popular tool to construct different types of micro- and nano-
protected saccharides, gel formation was observed and this
structured materials.3 LMOGs are known as distinct soft
1
observation prompted us to study the gelation property. H
materials and can self-assemble into various types of fibrils,
NMR spectra of N-glycosylated products 3–5 showed glycosidic
strands, and tapes in organic solvents via weak intermolecular
interactions.4 In an organogel medium, one dimensional (1D)
NH at around 5.0–6.0 ppm, the anomeric proton at around
4.5 ppm and the acetal proton changing with respect to the
supramoleculer fibers are bundled up together and entangled
protecting group, whereas in the case of 3f, 4f and 5f,
at nodes, so-called ‘‘junction points’’, to form three-
the glycosidic NH appeared below 5.0 ppm. The existence of
dimensional (3D) network structures, which entrap the solvent
the b-anomeric form was identified from coupling constant
values given in Table 1.
molecules. The nanostructured functional molecular assembly
thus created is a promising candidate for organic devices with
intriguing photo- and electrochemical functions.5 In the
Gelation studies
present case, H-bonding, CH–p, p–p stacking and dipole–
dipole interactions seem to play an important role in
self assembly. In order to obtain further insight into the
structure–function relationship of sugar-based organogelators,
we have generated a library of N-glycosylamines.
All gel samples were prepared by dissolving the gelator in a
solvent in such a way that it forms a homogenous solution.
The solution was allowed to cool down to room temperature,
whereby the gel is formed. The gelation ability of N-glycosyl-
amines [3(a–f)–5(a–f)] has been assessed by using ‘‘stable to
inversion of the container’’ method. The study includes
eighteen substituted aromatic-based saccharide derivatives
[3(a–f)–5(a–f)] in fourteen different organic solvents and the
results of gelation are summarised in Table 2. Recently, we
have reported4 the gelation of a novel class of 4,6-O-protected-
b-C-glycosides and sugar-pyridyl derivatives and the present
studies show gel formation of N-glycosylamines. In general,
protecting groups such as ethylidene, butylidene and
benzylidene present on the D-glucose moiety and the
substituents present on the aromatic ring showed remarkable
changes to the gelation process. Among the three different
Results and discussion
Synthesis and characterisation of N-glycosylamines
4,6-O-Butylidene-D-glucopyranose (BGP) 2a, 4,6-O-ethylidene-
D-glucopyranose (EGP) 2b and 4,6-O-benzylidene-D-glucopyranose
a Department of Organic Chemistry, University of Madras,
Guindy Campus, Chennai—600 025, India.
E-mail: tmdas_72@yahoo.com; Fax: +91 44-22352494;
Tel: +91 44-22202814
b Chemical Laboratory, Central Leather Research Institute (CSIR),
Adyar, Chennai-600 020, India
ꢀc
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Table 1 Synthesis of N-glycosylamines
Substituents
X
3
3
CGC %/g mLÀ1
d (ano-H), JH1,H2/Hz
d (gly-NH), JH1,H2/Hz
Yield (%)
Y
R
Compound
C3H7
3
a
b
H
H
F
Cl
H
CH3
H
H
F
Cl
H
CH3
H
H
F
Cl
H
Cl
F
1.5
1.0
—
—
1.5
—
1.3
1.5
1.1
—
1.5
—
4.51, 8.4
4.47–4.59, —
4.52–4.56, —
4.60, 8.4
4.50, 7.5
4.56–4.63
4.51, 8.4
4.47, 7.2
4.59, 5.1
4.60–4.74, —
4.77, 5.1
4.60, 7.4
5.36, 6.3
5.54, 6.6
4.66, 8.8
4.69, 8.5
4.56, 7.5
5.54, 8.7
5.71, 6.9
5.33, 6.3
5.63, 5.1
5.59, —
5.84, 6.9
4.56–4.63
5.60, 6.6
5.22, 6.6
5.93–5.95
5.60, 7.2
5.68, 6.6
4.68, 6.0
5.54, —
5.51, —
5.99, 6.0
5.63, 7.3
6.10, 6.6
4.63–4.75
89
81
78
92
85
91
85
86
81
87
84
87
81
83
79
91
89
92
ca
da
e
H
H
Br
H
Cl
F
H
H
Br
H
Cl
F
fa
a
CH3
4
b
c
da
e
fa
aa
b
C6H5
5
—
1.5
1.5
1.5
2.0
—
c
d
H
H
Br
H
e
fa
CH3
a
Denotes compound does not form gel. For all gelators, except gelators 4b, 4c and 4e, 1,2-dichlorobenzene was used to measure the CGC. For 4b
and 4c, o-xylene was used and for 4e benzene was used.
4,6-O-protected N-glycosylamines studied, BGP and EGP
derivatives possessing a halogen at the para position form gels
in both polar and non-polar solvents. Whereas in case of
BzGP, both ortho- and para-halogen substituted derivatives
form gels. The difference in gelation ability is mainly due to the
effect of the protecting group and it is as follows: 4c > 5c >
3a, 3b, 3e, 4a, 4b, 4e > 5b, 5d, 5e. The critical gelation
concentrations (CGC) of these compounds are given in
Table 1. Among the various polar and non-polar solvents
used for gelation, aromatic solvents viz., 1,2-dichlorobenzene
(1,2-DCB), o-xylene, m-xylene, benzene and toluene were
found to be the best solvents for the gelation process, which
may be attributed to a strong solute–solvent interaction.
Of all the gelators, N-glycosylamine 3b acts as an efficient
organogelator and gelates at lower concentrations
(CGC: 1%). The gelation ability of the organogelator has a
significant dependence on the protecting group and the
substitutents present on the aromatic ring. The greater
gelation ability of BGP and EGP is due to higher London
dispersion forces13 which exist between the alkyl chain groups.
However, in BzGP, p–p interactions seem to be largely
responsible for the gelation property. These results support
the fact that partially protected N-glycosylamines with
halogen substituted at the para position of the aromatic ring
have a greater ability to undergo gelation compared to the
substituents present at the ortho position. Moreover,
anisotropic interactions through H-bonding, CH–p, p–p
stacking and dipole–dipole interactions were also responsible
for the linear aggregation of LMOGs, allowing gel
formation. A pictorial representation of the groups in different
N-glycosylamines, which are responsible for gel formation is
shown in Fig. 1.
Single crystal X-ray diffraction (XRD) data of compounds
3d11 and 4d12 helps us to understand the p–p stacking and
H-bonding interactions that exists in different N-glycosylamines.
Free hydroxyl groups present at the C-2 and C-3 positions of
the glucopyranose ring are involved in the strong hydrogen
Fig. 1 Rationalization of different groups responsible for gelation in
different N-glycosylamines.
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Table 2 Gelation studies of N-glycosylamines
3 (R = C3H7) 4 (R = CH3)
5 (R = C6H5)
a
b
e
a
b
c
e
b
c
d
e
Solvent
C6H6
G
G
G
G
G
G
G
P
I
P
G
G
S
G
G
G
G
S
G
G
S
PG
PG
G
G
S
G
G
S
PG
G
G
G
G
G
G
S
G
G
G
G
S
PG
G
PG
G
G
G
G
S
G
G
S
G
G
G
G
S
G
S
S
G
G
G
G
P
CH3C6H5
NO2C6H5
p-Xylene
o-Xylene
m-Xylene
1,2-DCB
CHCl3
G
G
G
G
G
P
G
PG
PG PG
PG PG
G
S
S
G
G
G
PG
G
G
S
Fig. 3 p–p Stacking and H-bonding interactions of compound 4d. 12
CCl4
P
G
P
S
S
P
G
PG
P
S
S
PG PG PG
S
S
S
PG
S
S
P
S
PG
G
S
S
P
S
G
S
P
S
PG
S
i-PrOH
1,2-DCE
CH3CN
MeOH
G
G
G
P
S
G
S
S
S
S
G
S
S
S
S
S
PG PG PG
existence of surface tension in the gels. In addition, the
presence of a channel-like architecture with different bore size
is responsible for the gelation capacities.
S
P
PG
S
P
P
S
P
P
EtOH
S
P
S
S
Note: G—gelator, PG—partial gelator, S—solution, P—precipitation,
I—insoluble.
Thermoanalysis
To study the thermal properties of the organogelators and
gels, differential scanning calorimetry (DSC) experiments for
three different N-glycosylamines of 4,6-O-protected deri-
vatives (3a, 4b and 5c) were performed. In the case of 3a,
the enthalpy values and the melting point peak values are
found to be 191 J gÀ1 and 189 1C, and 248 J gÀ1 and 82 1C in
the solid and gel phases, respectively (Fig. 5). The enthalpy
values and the melting point peaks for compound 4b are
35 J gÀ1 and 128 1C in the solid phase, and 74 J gÀ1 and
99 1C in the gel phase. The peak appearing at around 112 1C
(DH = 138 J gÀ1) is due to the liberation of moisture. The
enthalpy values and melting point peak for compound 5c and
its gel were found to be 113.4 J gÀ1 and 143 1C, and 186 J gÀ1
bonding, thereby forming a chain of molecules (Fig. 2 and
Fig. 3). Although protecting groups are different in 3d and 4d,
the hydrogen bonding interactions are the same and one may
presume that just changing the protecting group and substituents
may not affect the hydrogen bonding. However, H-bonding of
the core sugar moiety remains unaltered in all the N-glycosyl-
amines. Thus, self-assembly of a gelator molecule depends
upon the nature of the protecting group and also the
substituents present in the aromatic ring.
Microscopy studies
In order to obtain visual insight into the aggregation modes,
scanning electron microscopy (SEM) images were obtained,
showing the presence of elongated nanofibers (Fig. 4). SEM
images of N-glycosylamines show well-defined 3D fibrous
networks. SEM images of compound 3b show the presence
of interwined thin sheets (Fig. 4b), whereas compounds 4e and
5d show elongated nanofibers around 310–350 nm with a bore
size range of 400–1000 nm. SEM images of compound 5c show
it forms a fibrous network with junction points (Fig. 4c). From
the SEM images (Fig. 4), the bore size of compound 3b
(CGC: 1%) is greater than that of 5c, 5d and 4e
(CGC: 1.5%), hence, compound 3b acts as a good gelator,
compared to the others. Three dimensional fibrous networks
hold the solvent molecules together, which is due to the
Fig. 4 SEM images of organogel formed from (a), 5d in 1,2-DCB;
(b), 3b in 1,2-DCE; (c), 5c in 1,2-DCB; (d), 4e in benzene; (e), 4e in
benzene (magnified) and (f), 4e in benzene (fiber and bore are labeled).
Fig. 2 p–p Stacking and H-bonding interactions of compound 3d.11
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Fig. 6 1H NMR of compound, 4a recorded at 27 1C in (a) CDCl3 + 2
drops of DMSO-d6 and (b) CDCl3 + 2 drops of DMSO-d6 + 4 drops
of D2O.
Fig. 5 DSC spectra of (a) 3a (gel formed from benzene), (b) 4b
(gel formed from 1,2-DCE) and (c) 5c (gel formed from toluene).
and 115 1C, respectively. These results indicate the thermal
stabilities of both gel and organogelator. DSC studies further
reveal that in the gel phase, the molecules were loosely packed
and the system moves from the most ordered state to a
less ordered state. The phase transition temperatures of
compounds, 3a, 4b and 5c and their corresponding gels are
given in Table 3. The melting temperatures of gelator and gel
are obtained from DSC experiments.
NMR studies
1H NMR studies were carried out for solution of 1.0–1.5% wt
of compounds 4a and 4f. In the case of compound 4a (Fig. 6)
the formation of the gel at 27 1C was accompanied by a
broadening and shifting of both aromatic and core sugar
proton signals. The 1H NMR spectrum of non-gelator 4f
shows slight broadening due to D2O exchange and not due
to gelation (Fig. 7); gelator molecules are assembled in the gel
network by means of hydrogen bonding, p–p stacking and
dipole–dipole interactions, which results in the broadening
of signals and due to long correlation times. The entire
broadening and shifting of signals in the organogelator 4a
shows the involvement of the aromatic ring, the sugar part and
also the protecting group, whereas, in the case of non-gelator
molecule 4f, these effects were not observed. Moreover, the
involvement of H-bonding in gelation can also be explained by
FT-IR and single crystal XRD studies.11,12
Fig. 7 1H NMR of compound, 4f recorded at 27 1C in (a) CDCl3 + 2
drops of DMSO-d6 and (b) CDCl3 + 2 drops of DMSO-d6 + 4 drops
of D2O.
N-glycosylamines both in solid and gel phase. FT-IR spectra
of the gel prepared from 3d in 1,2-DCB shows five prominent
characteristic peaks corresponding to nNH and nOH which
appear at 3578, 3446, 3352, 3235 and 3066 cmÀ1 (Fig. 8).
The degree of H-bonding was determined from the relative
intensities of the well known –OH stretching vibration at
around 3600 cmÀ1 which corresponds to free –OH and at
3300 cmÀ1 which corresponds to bonded –OH.14 The decrease
in intensity of the peak at 3578 cmÀ1 and the appearance of the
strong peaks at 3352, 3235 and 3066 cmÀ1 in the gel show the
presence of bonded –OH. However, in the solid, all four peaks
corresponding to the –OH group merged and appeared
as a broad band with shoulders at around 3355 cmÀ1. In
compound 5d, there is a prominent shift in wavelength
between gel and gelator, which clearly indicates the presence
of hydrogen bonding as shown in Fig. 8.
FT-IR studies
The role of hydrogen bonding in the process of gelation was
established with the help of FT-IR studies. In order to explain
the H-bonding, we have measured the FT-IR spectra of
Table 3 Melting temperatures of 3a, 4b and 5c in the solid and gel phases
Compound
Phase transition temperature of gelator/1C
Phase transition temperature of gel/1C
3a
4b
5c
189
128
143
82
99
115
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experimental results. Moreover, cis-Me–C6H4–NH2 and
cis-F–C6H4–NH2 have larger SE values than their corresponding
trans arrangements, as presented in Table 5, but practically
(i.e. considering the complete molecule) this arrangement is
highly unstable due to the repulsion among the various
groups.
Conclusion
In summary, we have reported the synthesis and gelation
properties of various sugar-based N-glycosylamines derived
from aromatic amines. The presence of p–p stacking and
H-bonding in N-glycosylamines was identified from single
crystal XRD studies.11,12 The gelation nature of these sugar
N-glycosylamine derivatives depends on the protecting groups
such as 4,6-O-butylidene, 4,6-O-ethylidene, 4,6-O-benzylidene
and halogen substituents. Variation in the protecting groups
and the position of the halogen atom alters the morphology
and the gelation abilities to a considerable extent as observed
from SEM analysis. Thermoanalysis of these gelators reveals
that molecules move from the most ordered state to a less
ordered state by forming a gel, whereby the melting temperature
becomes lower than the corresponding gelator. Moreover, the
presence of H-bonding was established from FT-IR and of
molecular aggregation by NMR studies. Computational
studies show the existance of dipole–dipole interactions,
CH–p and p–p stacking which play a vital role in gel
formation. Experimental results were reinforced with theore-
tical prediction. From these results, even a small tuning of
molecules can drastically alter their gelation properties.
Based on the present studies, one could conclude that
the presence of aliphatic or aromatic rings present at the
4,6-O-positions of the D-glucose unit of N-glycosylamines
result in gelation. The presence of halogen atoms is needed
for dipole–dipole interaction, whereas the methyl-substituted
do not form gels.
Fig. 8 FT-IR spectra of (a), gelator solvent (1,2-DCB); (b), 5d
(gel formed from 1,2-DCB) and (c), 5d (solid in KBr matrix).
Computational studies
In the present study, gelators 3b, 4b and 5b and non-gelators
3f, 4f, and 5f have been taken into account. All the systems
were optimized (without any geometrical constraint) by using
the M05-2X hybrid density functional method.15 The optimized
geometries were characterized as the minima on the potential
energy surface by frequency analysis. The stabilization energies
(SEs) are obtained using the equation,
SE = À[(Ecomplex À (Emonomer1 + Emonomer2)]
where Ecomplex, Emonomer1, and Emonomer2 are the total energies
of the complex and the monomers. The SE are corrected for
basis set superposition error (BSSE) using the method adopted
by Boys and Bernardi.16 All the calculations were performed
using the GAUSSIAN 03 (revision E.01) suite of programs.17
Due to the large system size and limited computational
facility, two approaches were used for calculation here:
(i) the complete system with the 6-31G* basis set; (ii) only
the active part of the system with the 6-311++G* basis set.
All the optimized dimeric complexes are shown in Fig. 9 and
their corresponding BSSE-corrected SE are depicted in
Table 4. Since the binding energies for gelator complexes are
comparatively larger than those of non-gelators, one can
predict that the dipole–dipole interactions (Fig. 9) play a vital
role in the gel formation. Fluorine substitution plays a
significant role in the high SE values because it interacts with
the glycosidic NH group of N-glycosylamines. In the case of
non-gelators, very weak CH–p interactions are observed,
causing the lower SE.
Experimental
General details
All reagents were purchased from Sigma Aldrich (benzaldehyde
dimethyl acetal), SRL (D-glucose) and Loba chemie
(butyraldehyde, paraldehyde, aromatic amines). Solvents used
for gelation studies were analytical grade and were purchased
from Qualigens, Sd-fine chemicals and SRL, India. NMR
spectra were recorded with a Bruker Avance 300 (300 MHz)
using TMS as internal standard. FT-IR studies were carried
out using a Perkin Elmer PE257 IR spectrometer. Thermal
transitions for gelators and gels were determined on a
NETZSCH DSC 204 instrument. The measurments were
carried out under nitrogen atmosphere using 50 mL sealed
aluminium sample pans. The temperature calibration for the
DSC was done using two standard materials (n-decane,
indium) and energy calibration by an indium standard
(28.45 J gÀ1). The gels were imaged with a HITACHI-S-
3400W scanning electron microscope. The samples were
gold-coated in such a way that the gold coating was less than
1 nm thick on average. Elemental analysis was performed by
using a Perkin-Elmer 2400 series CHNS/O analyser.
Other interactions are also important in gel formation,
therefore analysis of just the active part of the system has
been considered. Since this system size is small, a larger basis
set has been employed for the calculations. All the SE and
optimized geometries are shown in Table 5 and Fig. 10. In the
case of the benzene dimer (Bz–Bz), only the stable parallel-
displaced conformation is taken into account, the other
conformation, parallel, is less stable.4b The calculation
suggests that, apart from the dipole–dipole interacting sites,
various other possible interactions play a significant role
in the gel formation (Fig. 10). The Bz–Bz stacking energy is
1.67 kcal molÀ1 which reflects in the weak tail–tail interactions
in 5b, whereas in the case of 3b and 4b, head–head and
head–tail interactions were observed. Two different basis
sets were used here, but in the first case (i.e. complete
system consideration) results show good agreement with the
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Fig. 9 Optimized geometries of the complete dimer: grey = C, blue = N, red = O, white = H, yellow = F
concentration of 1.5% (gm LÀ1) and the mixture was heated
until the solid was dissolved. By this procedure, the solvent
boiling point becomes higher than that under standard
atmospheric pressure. The sample vial was cooled in air to
25 1C, left for 12 h at this temperature and then turned upside
down. When the gelator formed a clear or slightly opaque gel
by immobilizing the solvent at this stage, it was denoted by
‘‘G’’. Some of them form a partial gel, denoted PG. Some of
them are insoluble and some get precipitated, denoted by I and
P, respectively.
Table 4 Stabilization energy due to dipole interactions obtained at
the M05-2X level of calculation using 6-31G* basis set
S. No.
Compound
BSSE-corrected SE/kcal molÀ1
1
2
3
4
5
6
3b
4b
5b
3f
4f
5f
9.66948
6.98644
8.39269
2.54499
1.52937
3.25684
BGP, EGP and BzGP were synthesised by adopting the
literature procedures.6–9 N-Glycosylamines 3c, 3d, 4c, 4d, 5c
and 5d were synthesised and their purity confirmed using
different spectral techniques.10–12 Synthetic procedures and
spectral data for all other compounds are provided below.
Spectral characterization of gelators
Abbreviations, such as Sac and Ar, correspond to the saccharide
and aromatic groups, respectively.
4,6-O-Butylidene-N-(p-chlorophenyl)-b-D-glucopyranosyl-
amine (3a). Mp 186–188 1C; 1H NMR (CDCl3 + DMSO-d6):
d 7.09 (d, J = 8.4 Hz, 2H, Ar–H), 6.68 (d, J = 8.4 Hz, 2H,
Ar–H), 5.71 (d, J = 6.9 Hz, 1H, –NH), 5.10 (s, 1H, Sac-OH),
4.80 (s, 1H, Sac-OH), 4.57 (d, J = 4.8 Hz, 1H, Sac-H), 4.51
(t, J = 8.4 Hz, 1H, Sac-H), 4.12–4.16 (dd, J = 3.9 Hz, J =
9.6 Hz, 1H, Sac-H), 3.69 (t, J = 8.7 Hz, 1H, Sac-H), 3.26–3.51
(m, 4H, Sac-H), 1.60–1.67 (m, 2H, –CH2), 1.37–1.50 (m, 2H,
–CH2), 0.92 (t, J = 7.2 Hz, 3H, –CH3) ppm; 13C NMR
(CDCl3 + DMSO-d6): d 144.7, 128.3, 122.4, 114.6, 101.7,
86.2, 80.0, 73.6, 73.4, 67.9, 66.7, 35.8, 16.9, 13.5 ppm. Anal.
calcd for C16H22NO5Cl: C 55.90, H 6.45, N 4.07. Found C
56.18, H 6.62, N 4.19.
Synthesis
General synthetic procedure for the synthesis of compounds
3–5 is as follows:
To a solution of 1 mol of the 4,6-O-protected-b-D-
glucopyranose, (2a–c) in 10 ml of ethanol, 1.2 mol of the
substituted aniline was added. The reaction mixture was then
stirred at 50 1C for 10 min and at room temperature for 24 h.
The reaction was thereby followed through TLC. The solid,
which separates, was filtered off, washed with ethanol and
dried using diethyl ether.
Synthesis of gels
The gelation ability of N-glycosylamines was determined by
the ‘‘stable to inversion of the container’’ method.13 The
gelation properties have been tested with fourteen different
solvents as follows: gelator (1.5 mg) was mixed in a
close capped test tube with 1 ml of solvent to result in a
4,6-O-Butylidene-N-(p-fluorophenyl)-b-D-glucopyranosyl-
amine (3b). Mp 147–149 1C; 1H NMR (CDCl3 + DMSO-d6):
d 6.84–6.90 (m, 2H, Ar–H), 6.67–6.71 (m, 2H, Ar–H), 5.33
(d, J = 6.3 Hz, 1H, –NH), 4.99 (d, J = 4.2 Hz, 1H, Sac-H),
4.47–4.59 (m, 3H, Sac-H), 4.14–4.19 (dd, J = 4.2 Hz, J = 9.6 Hz,
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Fig. 10 Optimized geometries of the various interacting active parts of the gelators and non-gelators: grey = C, blue = N, red = O, white = H,
yellow = F.
1H, Sac-H), 3.69–3.73 (m, 1H, Sac-H), 3.28–3.54 (m, 4H, Sac-H),
1.61–1.67 (m, 2H, –CH2), 1.41–1.48 (m, 2H, –CH2), 0.92
13C NMR (CDCl3 + DMSO-d6): d 145.1, 131.1, 115.1, 109.5,
101.7, 90.0, 80.04, 73.6, 73.4, 67.9, 66.7, 35.8, 16.9, 13.5 ppm.
Anal. calcd for C16H22NO5Br: C 49.50, H 5.71, N 3.61. Found
C 49.27, H 5.92, N 3.45.
(t, J = 6.9 Hz, 3H, –CH3) ppm; 13C NMR (CDCl3
+
DMSO-d6): d 142.5, 115.4, 115.1, 114.8, 114.7, 102.1, 87.3,
80.3, 74.1, 73.9, 68.3, 67.1, 36.1, 17.2, 13.8 ppm. Anal. calcd
for C16H22NO5F: C 58.71, H 6.77, N 4.28. Found C 58.47, H
7.06, N 4.51.
4,6-O-Butylidene-N-(o-methylphenyl)-b-d-glucopyranosyl-
1
amine (3f). Mp 101–103 1C; H NMR (CDCl3 + DMSO-d6):
d 7.01–7.11 (m, 2H, Ar–H), 6.69–6.78 (m, 2H, Ar–H),
4.56–4.63 (m, 3H, Sac-H), 4.15–4.19 (dd, J = 4.2 Hz, J =
9.2 Hz, 1H, Sac-H), 3.73–3.79 (m, 1H, Sac-H), 3.41–3.55
(m, 3H, Sac-H), 3.34 (t, J = 8.9 Hz, 1H, Sac-H), 3.03
(s, 2H, Sac-H), 2.19 (s, 3H, Ar–CH3),1.62–1.68 (m, 2H, –CH2),
1.41–1.48 (m, 2H, –CH2), 0.92 (t, J = 7.4 Hz, 3H, –CH3) ppm;
13C NMR (CDCl3 + DMSO-d6): d 143.5, 129.7, 126.5, 122.4,
118.4, 111.4, 101.8, 86.1, 79.9, 73.8, 73.6, 68.0, 66.8, 35.8, 17.0,
16.87, 13.4 ppm. Anal. calcd for C17H25NO5: C 63.14, H 7.79,
N 4.33. Found C 62.89, H 7.87, N 4.50.
4,6-O-Butylidene-N-(p-bromophenyl)-b-D-glucopyranosyl-
amine (3e). Mp 118–120 1C; H NMR (CDCl3 + DMSO-d6):
1
d 7.21 (d, J = 8.7 Hz, 2H, Ar–H), 6.64 (d, J = 8.7 Hz, 2H,
Ar–H), 5.84 (d, J = 6.9 Hz, 1H, –NH), 5.22 (d, J = 4.2 Hz,
1H, Sac-H), 4.95 (d, J = 3.3 Hz, 1H, Sac-H), 4.56 (t, J =
5.1 Hz, 1H, Sac-H), 4.50 (d, J = 7.5 Hz, 1H, Sac-H), 4.11–4.15
(dd, J = 4.2 Hz, J = 9.4 Hz, 1H, Sac-H), 3.65–3.72 (m, 1H,
Sac-H), 3.29–3.50 (m, 4H, Sac-H), 1.59–1.67 (m, 2H, –CH2),
1.37–1.49 (m, 2H, –CH2), 0.92 (t, J = 7.3 Hz, 3H, –CH3) ppm;
Table 5 Stabilization energies due to all possible interactions obtained from M05-2X level of calculation using the 6-311++G* basis set
Entry
Interacting species
Nature of interaction
BSSE-corrected SE/kcal molÀ1
1
2
3
4
5
6
7
8
9
Bz (parallel displaced)
trans-Me–C6H4–NH2
cis-Me–C6H4–NH2
trans-F–C6H4–NH2
cis-F–C6H4–NH2
Bz–F–C6H4–NH2
Bz–Sug
Dimer
Dimer
Dimer
Dimer
Dimer
—
—
—
—
1.6739
3.3971
5.8217
5.1062
6.8986
2.8867
4.7878
5.9550
6.8595
F–C6H4–NH2–Sug
Me–C6H4–NH2–Sug
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4,6-O-Ethylidene-N-(p-chlorophenyl)-b-D-glucopyranosyl-
amine (4a). Mp 123–125 1C; 1H NMR (CDCl3 + DMSO-d6):
d 7.09 (d, J = 8.7 Hz, 2H, Ar–H), 6.71 (d, J = 8.7 Hz, 2H,
Ar–H), 5.60 (d, J = 6.6 Hz, 1H, –NH), 5.06 (d, J = 3.9 Hz,
1H, Sac-H), 4.74 (t, J = 4.0 Hz, 2H, Sac-H), 4.48–4.53
(dd, J = 6.9 Hz, J = 8.4 Hz, 1H, Sac-H), 4.11–4.16 (dd, J =
4.2 Hz, J = 9.9 Hz, 1H, Sac-H), 3.67–3.74 (m, 1H, Sac-H),
3.40–3.53 (m, 4H, Sac-H), 1.36 (d, J = 5.1 Hz, 3H, –CH3)
ppm; 13C NMR (CDCl3 + DMSO-d6): d 149.8, 133.6, 127.8,
119.8, 104.2, 91.5, 85.2, 78.9, 78.7, 73.0, 71.8, 25.2 ppm. Anal.
calcd for C14H18NO5Cl: C 53.25, H 5.75, N 4.44. Found C
53.46, H 5.63, N 4.61.
67.1 ppm. Anal. Cald for C19H20NO5Cl: C 60.40, H 5.34,
N 3.71. Found C 60.65, H 5.19, N 3.94.
4,6-O-Benzylidene-N-(p-fluorophenyl)-b-D-glucopyranosyl-
amine (5b). Mp 117–119 1C; 1H NMR (CDCl3 + DMSO-d6):
d 7.46–7.51 (m, 2H, Ar–H), 7.34–7.36 (m, 3H, Ar–H),
6.82–6.90 (m, 2H, Ar–H), 6.69–6.73 (dd, J = 4.5 Hz, J =
11.4 Hz, 2H, Ar–H), 5.53 (m, 1H, –NH), 5.18 (s, 1H, Sac-OH),
4.48–5.04 (m, 2H, Sac-H), 5.54 (d, J = 6.6 Hz, 1H, Sac-H),
4.30–4.34 (m, 1H, Sac-H), 3.45–3.95 (m, 5H, Sac-H) ppm; 13
C
NMR (CDCl3 + DMSO-d6): d 142.4, 133.8, 132.9, 131.3,
120.3, 120.0, 119.6, 119.5, 106.4, 92.2, 86.0, 78.9, 78.6, 73.6,
71.8 ppm. Anal. calcd for C19H20NO5F: C 63.15, H 5.58,
N 3.88. Found C 62.80, H 5.77, N 3.71.
4,6-O-Ethylidene-N-(p-fluorophenyl)-b-D-glucopyranosyl-
amine (4b). Mp 124–126 1C; 1H NMR (CDCl3 + DMSO-d6):
d 6.85–6.90 (d, J = 8.6 Hz, 2H, Ar–H), 6.67–6.72 (d, J =
8.5 Hz, 2H, Ar–H), 5.22 (d, J = 6.6 Hz, 1H, –NH), 5.01
(d, J = 3.9 Hz, 1H, Sac-H), 4.73–4.76 (m, 2H, Sac-H),
4.49–4.45 (t, J = 7.2 Hz, 1H, Sac-H), 4.14–4.17 (m, 1H,
Sac-H), 3.73–3.75 (m, 1H, Sac-H), 3.35–3.53 (m, 4H, Sac-H),
1.38 (d, J = 5.1 Hz, 3H, –CH3) ppm; 13C NMR (CDCl3 +
DMSO-d6): d 147.4, 120.3, 120.0, 119.6, 119.5, 104.1, 92.6,
85.2, 78.99, 78.7, 73.1, 71.8, 25.2 ppm. Anal. calcd for
C14H18NO5F: C 56.18, H 6.06, N 4.68. Found C 55.87, H
6.24, N 4.75.
4,6-O-Benzylidene-N-(p-bromophenyl)-b-D-glucopyranosyl-
amine (5e). Mp 135–137 1C; H NMR (CDCl3 + DMSO-d6):
1
d 7.50 (d, J = 2.4 Hz, 2H, Ar–H), 7.35 (d, J = 2.9 Hz, 2H,
Ar–H), 6.88 (d, J = 8.7 Hz, 2H, Ar–H), 7.22 (d, J = 8.7 Hz,
1H, Ar–H), 6.67 (d, J = 8.7 Hz, 1H, Ar–H), 6.10 (d, J =
6.6 Hz, 1H, –NH), 5.53 (d, J = 5.7 Hz, 1H, Sac-H), 4.56
(t, J = 7.5 Hz, 1H, Sac-H), 4.21–4.30 (m, 2H, Sac-H), 4.10
(d, J = 2.4 Hz, 1H, Sac-H), 3.12–3.72 (m, 5H, Sac-H) ppm;
13C NMR (CDCl3 + DMSO-d6): d 150.7, 142.6, 136.4, 133.8,
132.9, 131.4, 120.3, 114.3, 106.3, 91.3, 86.1, 83.4, 78.6, 73.6,
71.8 ppm. Anal. calcd for C19H20NO5Br: C 54.04, H 4.77, N
3.32. Found C 54.36, H 4.71, N 3.42.
4,6-O-Ethylidene-N-(p-bromophenyl)-b-D-glucopyranosyl-
1
amine (4e). Mp 127–129 1C; H NMR (CDCl3 + DMSO-d6):
4,6-O-Benzylidene-N-(o-methylphenyl)-b-D-glucopyranosyl-
1
d 7.26 (d, J = 8.7 Hz, 2H, Ar–H), 6.62 (d, J = 8.7 Hz, 2H,
Ar–H), 5.68 (d, J = 6.6 Hz, 1H, –NH), 5.20 (d, J = 3.9 Hz,
1H, Sac-H), 4.84 (d, J = 3.4 Hz, 1H, Sac-H), 4.77 (d, J =
5.1 Hz, 1H, Sac-H), 4.52–4.58 (t, J = 7.8 Hz, 1H, Sac-H),
4.15–4.19 (dd, J = 4.2 Hz, J = 10.2 Hz, 1H, Sac-H), 3.32–4.19
(m, 5H, Sac-H), 1.40 (d, J = 4.8 Hz, 3H, –CH3); 13C NMR
(CDCl3 + DMSO-d6): d 145.3, 131.6, 115.4, 110.1, 99.3, 80.2,
73.9, 73.7, 68.2, 66.9, 20.3. Anal. calcd for C14H18NO5Br: C
46.68, H 5.04, N 3.89. Found C 46.45, H 5.26, N 4.03.
amine (5f). Mp 99–101 1C; H NMR (CDCl3 + DMSO-d6):
d 7.51 (d, J = 4.5 Hz, 2H, Ar–H), 7.36 (d, J = 3.9 Hz, 3H,
Ar–H), 7.02–7.12 (m, 2H, Ar–H), 6.70–6.81 (m, 2H, Ar–H),
5.54 (d, J = 8.7 Hz, 1H, –NH), 5.02 (s, 1H, Sac-OH),
4.63–4.75 (m, 3H, Sac-H), 4.32–4.37 (m, 1H, Sac-H),
3.48–3.85 (m, 4H, Sac-H), 2.87 (m, 1H, Sac-H), 2.20 (s, 3H,
Ar-CH3) ppm; 13C NMR (CDCl3 + DMSO-d6): d 148.2,
141.6, 134.2, 133.1, 132.2, 131.0, 130.6, 126.9, 122.9, 116.0,
105.8, 91.0, 85.3, 78.3, 78.1, 73.0, 71.2, 21.6 ppm. Anal. calcd
for C20H23NO5: C 67.21, H 6.49, N 3.92. Found C 67.55,
H 6.23, N 3.78.
4,6-O-Ethylidene-N-(o-methylphenyl)-b-D-glucopyranosyl-
1
amine (4f). Mp 129–131 1C; H NMR (CDCl3 + DMSO-d6):
d 7.02–7.11(m, 2H, Ar–H), 6.69–6.79 (m, 2H, Ar–H), 4.98
(d, J = 4.2 Hz, 1H, Sac-H), 4.73–4.78 (dd, J = 4.8 Hz,
J = 9.9 Hz, 1H, Sac-H), 4.68 (d, J = 6.0 Hz, 1H, Sac-H), 4.60
(t, J = 7.4 Hz, 1H, Sac-H), 4.50 (d, J = 2.7 Hz, 1H, Sac-H),
4.15–4.19 (m, 1H, Sac-H), 3.73–3.79 (m, 1H, sac-H), 3.50–3.57
(m, 4H, Sac-H), 2.19 (s, 3H, Ar–CH3), 1.39 (d, J = 4.8 Hz,
3H, –CH3) ppm; 13C NMR (CDCl3 + DMSO-d6): d 143.9,
130.1, 126.9, 122.8, 118.8, 111.8, 99.4, 86.3, 80.3, 74.3, 74.1,
68.3, 67.0, 20.3, 17.4 ppm. Anal. calcd for C15H21NO5:
C 61.00, H 7.17, N 4.74. Found C 61.13, H 7.36, N 4.60.
Acknowledgements
T.M.D. acknowledges financial support from the Department
of Science and Technology, New Delhi, India. We thank the
Department of Science and Technology, New Delhi for the
300 MHz NMR facility under FIST scheme to the Department
of Organic Chemisty, University of Madras, Chennai, India.
S.N. thank UGC, New Delhi for research fellowship.
References
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