Preparation of alkyl α- and β-D-glucopyranosides, thermotropic properties and X-ray analysis

Article abstract of DOI:10.1016/S0008-6215(98)00302-4

Monohydrates of heptyl to decyl α-D-glucopyranosides as obtained from product mixtures of the Fischer glucosylation were crystallized from water at the Krafft point. The results of the single-crystal X-ray analysis of anhydrous α anomers and their monohydrates provide for a better understanding of crystal formation and stability of their hydrates. The preparation of alkyl β-D-glucopyranosides-without concomitant formation of α anomers as by-products-has been described. The thermotropic properties have been investigated for the α compounds and their monohydrates, and for the β-D-glucopyranosides. Copyright (C) 1998 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(98)00302-4

Carbohydrate Research 314 (1998) 177–187
Preparation of alkyl a- and b-
D
-glucopyranosides,
ꢀ
thermotropic properties and X-ray analysis
a
a
c
a
Volker Adasch , Bettina Hoffmann , Wolfgang Milius , Gerhard Platz ,
b,
Gundula Voss *
a
Department of Physical Chemistry I, Uni6ersity of Bayreuth, D-95440 Bayreuth, Germany
Department of Organic Chemistry II, Uni6ersity of Bayreuth, D-95440 Bayreuth, Germany
b
c
Department of Inorganic Chemistry I, Uni6ersity of Bayreuth, D-95440 Bayreuth, Germany
Received 2 March 1998; accepted 12 November 1998
Abstract
Monohydrates of heptyl to decyl a-
D
-glucopyranosides as obtained from product mixtures of the Fischer
glucosylation were crystallized from water at the Krafft point. The results of the single-crystal X-ray analysis of
anhydrous a anomers and their monohydrates provide for a better understanding of crystal formation and stability
of their hydrates. The preparation of alkyl b- -glucopyranosides—without concomitant formation of a anomers as
D
by-products—has been described. The thermotropic properties have been investigated for the a compounds and their
monohydrates, and for the b- -glucopyranosides. © 1998 Elsevier Science Ltd. All rights reserved.
D
Keywords: -Glucopyranosides; Hydrates; Separation; Syntheses; Liquid crystals; X-ray
D
ranosides is a multistep procedure developed
1
. Introduction
Alkyl -glucosides have recently attracted
by Koenigs and Knorr [10]. A valuable mod-
ification of the classical Koenigs–Knorr reac-
tion was described by Kunz and Harreus [11].
It is shown in this paper that this method is
D
attention as surfactants with special properties
desirable to customers. They are used e.g., in
cosmetic products, as food emulsifiers, textile
lubricants, drug carriers and as solubilizing
agents for membrane proteins [1–5]. One re-
markable advantage is their biodegradability
best suited for the preparation of alkyl b- -
D
glucopyranosides.
Alkyl glucosides form micelles in water
above their critical micellar concentration
(CMC) [8,12,13]. The solubility of surfac-
tants—as a function of temperature—is char-
acterized by the Krafft point (minimal
temperature where the surfactants form mi-
celles). Below that temperature, the surfactant
precipitates from solution because its solubil-
ity becomes lower than the CMC [14]. The
Krafft points of alkyl glucosides are higher for
a anomers (considerably above room tempera-
ture) than for the corresponding b anomers
[
2,3].
The first preparation of alkyl glucosides as
anomeric mixtures was described more than
one hundred years ago by Emil Fischer [6].
This procedure provided mainly alkyl a-
copyranosides [7–9]. The classical method for
D-glu-
the directed preparation of alkyl b- -glucopy-
D
ꢀ
Dedicated to Professor Dr H. Gerlach.
(
50 °C). Consequently, it should be possible
*
Corresponding author. Fax: +49-921-53474.
E-mail address: gundula.voss@uni-bayreuth.de (G. Voss)
to separate, by crystallization, from water an
0008-6215/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(98)00302-4

178
V. Adasch et al. / Carbohydrate Research 314 (1998) 177–187
excess of the sparingly soluble a anomers from
mixtures of anomers at temperatures between
their Krafft points [15].
2. Results and discussion
Alkyl h-
drates.—Alkyl a-
pared according to the procedure of Fischer [6].
In this one-step synthesis, a 5% solution of
D
-glucopyranosides and monohy-
-glucopyranosides were pre-
We have systematically explored this eco-
nomically superior approach to the separation
of certain a anomers from aqueous solutions.
It was found that these surfactants form well-
defined hydrates, a fact that seems to have
eluded most investigators in this field. Until
now, only Barrall and co-workers [16] have
made a general remark, pointing out the impor-
tance of water in the crystallization process, and
Dorset and Rosenbusch [17] used such a
D
D-glucose in dioxane was used for the reaction
with the respective alcohol. Sulfuric or p-tolue-
nesulfonic acid monohydrate was used as cata-
lyst. The formation of undesired oligosaccha-
rides and their alkyl glycosides was reduced by
using up to a 12-fold molar amount of the
alcohol, the excess of which was removed by
subsequent distillation. By-products were re-
moved (after neutralization and evaporation of
solvent) by filtration through the 20-fold
method for the crystallization of octyl a- -glu-
D
copyranoside without being aware that they
possibly obtained a hydrate. It is assumed that
the preferred crystallization of alkyl a- -glu-
D
amount of silica gel. Thus, alkyl a/b- -glucopy-
D
copyranosides originates from optimal crystal
packing, i.e., when a maximum number of
hydrogen bonds are present [9,17,18].
Traditionally, organic solvents have been
used for crystallization of alkyl glucopyra-
nosides [8,19]. This paper describes the prepara-
tion and some properties of compounds 1a–g
and 2a–g and some monohydrates of the for-
mer.
ranosides were obtained in a ratio up to 7:3 [7]
in about 70% yield. For separation of the major
components and their purification, water was
used as solvent. Monohydrates of a anomers
1
b to 1e were isolated in yields of up to 34%
aq
aq
when an aqueous solution (5–10%) was cooled
from about 70 to 4 °C (i.e., below the Krafft
point) (see Table 1). The supernatants which
contain all of the b anomers were found to be
about 1:1 mixtures of a and b compounds.
The mixtures of anomers 1a/2a, 1f/2f and
1
g/2g were separated by conventional crystal-
lization from organic solvents to get the spar-
ingly soluble a compounds as pure anhydrous
substances. The argument is, that the Krafft
point of 1a is too low for crystallization from
water. Those of the a/b anomers 1f/2f and
Table 1
Physicochemical properties of alkyl a-D-glucopyranoside monohydrates 1b –1e
aq aq
2
0
a
Entry
[a] , MeOH
Water, %
KF-Titration)
Elemental analysis
Krafft points (°C)
D
(
Calcd
% C
Found
% C
Calcd
Found
% H
% H
1
1
1
1
baq C H O +117.0° (c 1.00)
6.09
5.81
5.56
5.33
6.10
5.70
5.67
5.33
52.69
54.18
55.54
56.78
9.52
9.74
9.94
10.13
52.71
53.82
55.40
56.61
9.55
9.68
9.78
10.03
34
40
43
43
13
28
7
b
caq C H O +120.0° (c 0.93)
14
30
7
daq C H O +107.8° (c 1.00)
15
32
7
c
eaq C H O +104.0° (c 1.07)
16
34
7
a
Krafft points were determined by heating a mixture of surfactant and water in a probe tube (see Materials and General
Methods). The solution temperature corresponds to the Krafft point of the surfactant [14]. The Krafft point of 1a is 55 °C.
b
4
0 °C [18].
c
Krafft points for 2e: 22.5 °C, 1f: 53 °C, 2f: 37.5 °C [21].

V. Adasch et al. / Carbohydrate Research 314 (1998) 177–187
179
Table 2
successfully removed by crystallization from
water or an organic solvent to recover about
an additional 10% of mostly pure a and b
anomers. The use of anion-exchange resin for
separation of the a/b glucopyranosides is also
described [20]. We chromatographed success-
fully a mixture of 1b/2b on Dowex 1×2
Transition points of alkyl a-D-glucopyranoside monohydrates
a
1
b –1e and anhydrous alkyl a-D-glucopyranosides 1b–1e
aq
aq
b
c
d
e
d
Lit
Entry
(tp) cp (°C) (mp) cp
°C)
(mp) cp
(°C)
(
g
1
1
1
1
1
1
1
1
baq (n=7) (48.8–51.6)
(51.4) 97.9
f
9
5.1
−
i
(OH -form) with water. Contrary to the sep-
b (n=7)
(53.7–55.3)
(52–54)
h
99.9
aration on silica gel, the a anomer 1b eluted
g
g
g
caq (n=8) (57.3–57.8)
(54.9) 120.1
first, followed by the b anomer 2b.
f
1
17.5
Representative for the synthesis, separation,
j
c (n=8)
(73.0–74.4)
(73) 117
h
and isolation, the preparation of decyl a- -
D
1
17.4
glucopyranoside monohydrate (1e ) accord-
daq (n=9) (59.0–59.2)
(57.0) 128.0
aq
f
1
30.0
ing to Fischer with the b anomer 2e as
i
d (n=9)
(67.5–68.6)
(69–70)
by-product has been described in detail.
h
1
26.2
Alkyl i-
rected synthesis of anomerically pure alkyl
-glucopyranosides, we adapted the well-
D
-glucopyranosides.—For the di-
eaq (n=10) (66.2–67.6)
(70.3) 134.2
f
1
35.2
k
e (n=10)
(77.0–77.2)
(76) 138
b-D
h
1
38.3
known Koenigs–Knorr synthesis as modified
by Kunz and Harreus [11]. Briefly, we reacted
a
Determined between crossed polarizers.
n: alkyl-chain length.
tp: loss of H O, proved by thermogravimetry.
cp: clearing point (anisotropic[isotropic liquid).
mp: melting point (solid[anisotropic liquid).
Water.
Unknown origin (see text), DSC [16].
Lyophilized.
b
c
d
e
f
tetrapivaloyl a- -glucosyl bromide [11] in di-
D
ethyl ether with the appropriate alcohol in the
presence of molecular sieves and silver car-
bonate to obtain the peracylated glucosides.
After chromatographic purification on silica
gel, pivaloyl moieties were removed by
NaOMe-catalyzed transesterification with
methanol. Treatment of the resulting mixture
with ion-exchange resin in water or methanol,
followed by lyophilization (water) or distilla-
tion (methanol), yielded the anomerically pure
2
g
h
i
From EtOAc [19].
From EtOAc (DSC) [9].
Unknown origin [18].
j
k
1
g/2g are too close for a convenient separa-
b-
D
-glucopyranosides 2a, 2e to 2g in up to
tion from water (see Table 1).
7
5% yield based on the acylated glucosyl bro-
With the exception of 1c , the isolated
aq
D
-glucopyranoside monohydrates 1baq
mide (see Table 3). By this procedure, we
avoided the traditional final purification of
alkyl a-
and 1d to 1eaq have not previously been
aq
alkyl b- -glucopyranosides on silica gel with
D
described. Storage in a desiccator over KOH
for several days or lyophilization transformed
the hydrates into the anhydrous compounds
polar eluent [9,12].
Representative for the synthesis of alkyl
b-
modified Koenigs–Knorr procedure, the
-glucopyranoside (2a)
D
-glucopyranosides according to the
1
b to 1e; for physical properties see Tables 1
and 2.
preparation of hexyl b-
D
To isolate also b anomers and residual a
including the characterization of the tetrapi-
valoyl intermediate has been described in
detail.
anomers from the supernatants, we chro-
matographed them on the 50 to 75-fold
amount of silica gel (9:1 EtOAc–EtOH). The
Thermotropic properties and single-crystal
alkyl b-
D
-glucopyranosides are less polar and
X-ray structure analysis of alkyl a-
ranosides.—Alkyl a/b- -glucopyranosides ex-
hibit phase transitions first to liquid crystals
mp, melting point) upon heating before they
melt to isotropic liquids (cp, clearing point)
D-glucopy-
eluted first (R about 0.40), followed by the
f
D
more polar a anomers (R about 0.35). The
enriched fractions typically still contained
some of the undesired anomers. These were
f
(

180
V. Adasch et al. / Carbohydrate Research 314 (1998) 177–187
[
16,20,24–26]. Our study of transition points
monohydrates 1baq to 1eaq that we observed,
but detailed preparation conditions are not
described.
and X-ray analyses of some alkyl a- -glu-
D
cosides and their monohydrates may elicit in-
sights into their thermotropic properties.
These observations may add some knowledge
to the formation of liquid crystals of these
substances. Both the spontaneous loss of crys-
tal water of the monohydrates 1b to 1e and
According to previous reports [27], the tran-
sition to the liquid crystal phase of the alkyl
a- -glucopyranosides is accompanied by a
D
partial melting of the hydrophobic part of the
crystal structure.
aq
aq
the loss upon heating have been monitored
and interpreted. The melting points of the
hydrates are lower compared to those of the
anhydrous substances [26]. Focher and co-
workers [9] found a lower temperature for the
gel–liquid crystal transition of hydrated octyl
a- -glucopyranoside (stored at 90% relative
humidity) relative to the anhydrous
compound.
The hydrocarbon chains are densely packed
in the anhydrous compounds. The incorpora-
tion of a water molecule increases the bonding
energy between the sugar groups. Due to ster-
ical hindrance the hydrocarbon chains lose
their optimal packing and become somewhat
crossed. This effect reduces the lattice energy
of the hydrocarbon chains and explains the
low stability of the monohydrates (loss of
water).
D
The transition points of the thermotropic
substances 1b to 1e and their monohydrates
Structure descriptions
1
baq to 1eaq have been observed between
Hexyl h- -glucopyranoside (1a). The anhy-
D
crossed polarizers in open test tubes and ex-
drous hexyl a- -glucopyranoside (1a) crystal-
D
amined side by side. The hydrates 1b to 1eaq
lizes in the same space group (P2 ) as the
aq
1
have distinctively lower transitions points (loss
of crystal water, proved by thermogravimetry)
in relation to the melting points of the anhy-
drous substances 1b to 1e, whereas the clear-
ing points do not differ substantially (see
Table 2). Barrall and co-workers [16] pub-
other known anhydrous compounds 1c, e [27–
29] (see Figs. 1–3). The unit cell parameters
are comparable to those of the anhydrous
octyl and the decyl compound 1c, e. In con-
trast to the hydrates, the 2 screw axes point
1
parallel to the plane built by the hydrocar-
bons, which is also in analogy with the known
anhydrous a anomers. This structural feature
lished transition points of alkyl a-
D
-glucopy-
of the
ranosides
confirming
those
Table 3
Physicochemical properties of alkyl b-
D
-glucopyranosides 2a–2g
a
20
D
Entry
mp (°C)
Found
[a] , MeOH (or as mentioned)
R (9:1 EtOAc–EtOH)
f
Lit
Found
Lit
b
c
e
c
c
2a (n=6)
2b (n=7)
2c (n=8)
2d (n=9)
2e (n=10)
2f (n=12)
2g (n=14)
(88.1) 89.0
88–91
74–77
65–99
−33.4° (c 1.02)
−32.3° (c 1.13)
−24.2° (c 1.32)
−25.8° (c 1.06)
−25.4° (c 1.15)
−24.1° (c 1.06)
−23.9° (c 1.02)
−33.7°
0.36
0.37
0.38
0.39
0.40
0.41
0.43
d
e
(74.5–74.9) 78.3
(77–83) 99–101
−34.2° (H O)
2
f,g
g
c
−30.3°
−28.8°
−27.8°
−24.7°
b,h
c
c
c
h
c
(66.2)118.7–119.0
65–118
75–130
77–137
f
c
(65–70) 130
(73–75) 135
f
c
f
i
(64.8)147.1
82.0–147.5
a
n: Alkyl-chain length.
b
c
d
e
f
From EtOAc–Et O (1:1).
2
From EtOAc [22].
Lyophilized.
From EtOH [23].
From acetone.
Containing 5% of 1c.
Containing 5% of 1d.
DSC [1].
g
h
i

V. Adasch et al. / Carbohydrate Research 314 (1998) 177–187
181
Fig. 1. Packing plot of hexyl a-
D
-glucopyranoside (1a), perspective view along the b-axis.
is in agreement with the findings concerning
the formation of liquid crystal phases by
\O …H-6A−O-6…H-4A−O-4…H-3A
W
−
O-3…H −O −H …O-2−H-2A.
W
W
W
alkyl a-
edge, the hexyl a-
first compound in the series of alkyl a-
D
-glucopyranosides. To our knowl-
-glucopyranoside is the
-glu-
D
As in other known hydrates of this type
(e.g., octyl a- -glucopyranoside hemihydrate
D
D
copyranosides showing liquid crystal behav-
ior. Analogously to the other anhydrous
glucopyranosides, the hydrogen bridging
bonds at the hydrophilic end of the molecule
form a three-dimensional network without
any water:
and the monohydrate 1c [28,29]), the 2 screw
aq
1
axes of 1b point perpendicularly to the plane
aq
built by the alkyl carbons.
By comparing the crystal structures of anhy-
drous hexyl a-
octyl a-
those of the monohydrates 1b /1c , the main
D
-glucopyranoside (1a) and
D
-glucopyranoside (1c) [28,29] with
aq
aq
O-6−H-6A···O-4−H-4A···O-3−H-3A···O-2
difference is seen to be in the arrangement of
the alkyl chains. Whereas, in all the anhydrous
glucopyranosides, the hydrophobic chains lie
parallel to one another forming the non-polar
layer, in the monohydrates 1baq and 1caq
[28,29] the interwoven chains cross each other.
We are now able to state that the crossing
angle decreases with increasing chain length,
being about 150° in the heptyl compound 1baq
−
H-2A···O-6−
Heptyl h- -glucopyranoside monohydrate
-glucopyra-
D
(
1b ). The structure of heptyl a-
D
aq
noside monohydrate (1b ) consists of alter-
aq
nating regions of polar and non-polar groups
in analogy to the octyl monohydrate 1caq
[
28,29] (see Figs. 4 and 5). This arrangement
of the molecules constitutes close packing of
fully extended alkyl chains between hydro-
gen-bonded layers of glucopyranoside rings.
Inspecting the unit cells of the heptyl- and
the octyl-monohydrates 1baq and 1caq reveals
great similarity concerning the orientation of
the molecules relative to the cell axes and the
metric except for the monoclinic b-angle. The
difference in the b-angles can be explained by
the shorter alkyl-chains in the heptyl com-
pound. Schematically, pressure against oppo-
site corners of the unit cell will have the same
effect as shortening the alkyl-chains. The wa-
ter molecule plays a decisive role in building
the hydrogen bond scheme at the glucopyra-
noside rings. The hydrogen bond arrange-
ment is
and about 130° in the octyl compound 1caq.
3. Experimental
Materials and general methods.—If not oth-
erwise mentioned, the physical constants of the
prepared substances and references are given in
Tables 1–3. TLC was carried out on Silica Gel
60 F254 glass plates (E. Merck); compounds
were visualized by concd H SO /180 °C (]3%
2
4
b anomer detectable in a anomer). Column
chromatography was performed on Silica Gel
60 (E. Merck) and an anion-exchange chro-
−
matography on Dowex 1×2, OH -form 200–
400 mesh. Melting points and Krafft points
were determined with a B u¨ chi 510 apparatus.

182
V. Adasch et al. / Carbohydrate Research 314 (1998) 177–187
Fig. 2. Packing plot of hexyl a-D-glucopyranoside (1a), perspective view along the a-axis.
Transition points were estimated with test tubes
between crossed polarizers. Optical rotations
were measured with a Perkin–Elmer 241 polar-
imeter. Crystal water was determined with a
KF-coulometer-684 (Metrohm) with voltam-
metric endpoint determination. For CMC mea-
surements, a Lauda ring tension apparatus (TE
tometer with graphite-monochromatic Mo Ka
radiation (u 71.073 pm); the intensity of the
primary beam was controlled by monitoring
three reference reflections every 100 reflections.
The structures were solved by direct methods
and refined against F by full-matrix least
squares using the program package SHELXTL
V.4.2 [30,31]. For crystal structure analyses,
the positions of the hydrogen atoms were
1
C) and a Lauda drop volume tension appara-
tus (TVT 1) were used. IR spectra were
recorded on a Paragon 1000 FT IR-spectrom-
geometrically calculated and refined with fixed
˚
2
1
U values (0.08 A ) applying the riding
eter (Perkin–Elmer) and H (270.17 MHz) and
1
3
C (67.94 MHz) NMR spectra on a JEOL
JNM-EX 270 instrument in CD OD as solvent,
3
if not mentioned otherwise; chemical shifts (l)
measured from the appropriate residual solvent
signal are referenced to Me Si; quantitative
4
compositions of anomeric mixtures were calcu-
lated from the ratio of the H-1-signal integrals
(
doublets at 4.6790.10 ppm for the a-
D
-glu-
copyranosides and at 4.1590.20 ppm for b-
D
-
13
glucopyranosides);
C signal multiplicities
were determined from DEPT spectra. In the
case of X-ray analysis reflection intensities were
estimated at 296 K on a Siemens P4 diffrac-
Fig. 3. ORTEP drawing of the molecule of hexyl a-
ranoside (1a).
D-glucopy-

V. Adasch et al. / Carbohydrate Research 314 (1998) 177–187
183
chromatography (9:1 EtOAc–EtOH) and re-
crystallization, an additional 3.99 g (7%,
EtOAc) of 1a and 5.1 g (9%, 1:1 EtOAc–
Et O) of hexyl b-
D
-glucopyranoside (2a) were
2
isolated.
Determination of the crystal structure of
-glucopyranoside (1a). The crystal of
C H O (264.32) suitable for X-ray analysis
hexyl h-
D
1
2
24
6
was a colorless platelet of size 0.60×0.30×
0
.15 mm. The compound crystallized mono-
clinically in the space group P2 with the
1
lattice parameters a=511.5(2), b=758.9(2),
c=1779.5(4) pm, i= 96.11(3) , V=
o
6
3
6
86.8(4)×10 pm , and Z=2. D is 1.278 g
−3
Fig. 4. Packing plot of heptyl a-
D
-glucopyranoside monohy-
x
drate (1b ), perspective view along [101].
aq
cm . 3727 Reflections in the range 3–55° (2
Theta) were collected, 3157 were independent,
model. Elemental analyses were carried out by
the Microanalytical Laboratory Ilse Beetz, D-
and 3040 were assigned to be observed [F ]
o
2
|(F )]. The refinement of 164 parameters
o
9
6317 Kronach.
Hexyl h- -glucopyranoside (1a) and hexyl
-glucopyranoside (2a).— -Glucose (40.4
with anisotropic displacement coefficients for
D
all non-hydrogen atoms converged at R/wR=
−
1
2
i-
D
D
0
.058/0.059 [w =| (F )]. The positions of
o
g, 224 mmol) was reacted with hexanol (275
mL, 226 g, 2.21 mol) in dioxane (800 mL)
with p-toluenesulfonic acid monohydrate (7.0
g, 37 mmol). After neutralization and evapo-
ration of the solvent, the excess of hexanol
was azeotropically distilled with water at 20
Torr. The residue was suspended in water and
extracted twice with toluene. The aqueous
layer was lyophilized and filtered on silica gel
the hydrogen atoms connected to oxygen
could be located by successive Fourier synthe-
ses; those which are connected to carbon were
calculated geometrically. The max/min resid-
˚
−3
ual electron density was 0.42/–0.24 e A
Heptyl h- -glucopyranoside monohydrate
(1b ) and heptyl i- -glucopyranoside (2b).
-Glucose (40.0 g, 222 mmol) was reacted
.
D
D
aq
—
D
with heptanol (373 mL, 307 g, 2.64 mol) in
dioxane (800 mL) and 96% H SO (2.0 mL,
(
(
9:1 EtOAc–EtOH): 40.05 g (68%) of 1a/2a
2
4
67:33). The product was recrystallized twice
3.7 g, 37 mmol). The mixture was subse-
quently neutralized and concentrated in vac-
uum. The residue was filtered through silica
gel (9:1 EtOAc–EtOH): 42.2 g (68%) of 1b/2b
(68:32). The mixture was recrystallized twice
from EtOAc to yield 12.84 g (22%) of anomer-
ically pure hexyl a- -glucopyranoside (1a) as
colorless small crystals: mp (58.6) 67.0 °C, lit
7
+
4
1
D
2
0
0 °C [8]; [a] +132.4° (c 0.99, MeOH), lit
D
1
132.1° (MeOH) [8]; R 0.33; H NMR: l
from water to give 6.88 g (10%) heptyl a- -
D
f
13
glucopyranoside monohydrate (1b ) as color-
.67 (d, 1 H, J 3.6 Hz, H-1 ); C NMR: l
aq
glc
1
less crude needles. H NMR: l 4.71 (d, 1 H, J
.6 Hz, H-1 ); C NMR: l 100.06 (d, C-1 ).
00.06 (d, C-1 ); CMC: 0.136 M, lit 0.20 M
glc
1
3
3
[
8]. From supernatants (28.2 g), following
glc
glc
From supernatants (29.05 g), after chromatog-
raphy (9:1 EtOAc–EtOH) and recrystalliza-
tion, 5.33 g (8%, H O) of 1b and 10.0 g of
2
aq
heptyl a/b-
D
-glucopyranosides (1b/2b, 7:93;
1
:1 EtOAc–Et O) were isolated as oily
2
products.
For analysis of 2b, 605 mg (1b/2b, 62:38)
was separated on Dowex 1×2 (170 g) with
H O as eluent to give 210 mg of pure heptyl
2
b- -glucopyranoside 2b as a white powder
D
Fig. 5. ORTEP drawing of the molecule of heptyl a-
ranoside monohydrate (1baq).
D-glucopy-
1
after lyophilization. H NMR: l 4.14 (d, 1 H,

184
V. Adasch et al. / Carbohydrate Research 314 (1998) 177–187
1
3
J 7.9 Hz, H-1glc); C NMR: l 104.37 (d,
1d/2d (62:38). The product was recrystallized
C-1 ).
twice from water to yield 12.5 g (17%) of
glc
Determination of crystal structure of heptyl
-glucopyranoside monohydrate (1b ). The
crystal of C H O ·H O (296.36) suitable for
X-ray analysis was a colorless needle of di-
mensions 0.60×0.20×0.07 mm. The com-
pound crystallized monoclinically in the space
group C with the lattice parameters a=
830.4(4), b=497.1(2), c=1962.0(4) pm, i=
15.11(3)°, V=1616.4(8)×10 pm , and
nonyl a- -glucopyranoside monohydrate
D
1
h-D
(1d ) as colorless small needles. H NMR: l
aq
aq
13
4.75 (d, 1 H, J 3.8 Hz, H-1 ); C NMR: l
1
3
26
6
2
glc
100.00 (d, C-1 ). From supernatants (27.9 g),
glc
after chromatography (9:1 EtOAc–EtOH)
and recrystallization was isolated: 5.7 g (8%,
H O) 1d and 4.04 g (6%, 1:1 EtOAc–Et O)
2
2
aq
2
1
1
nonyl b-
D
-glucopyranoside (2d) as a white
6
3
1
powder, containing 5% of 1d. H NMR: l
1
3
Z=4. 2460 Reflections in the 2 Theta range
–55° were measured, 2267 were independent,
and 1740 were assigned to be observed [F ]
4.16 (d, 1 H, J 7.3 Hz, H-1 ); C NMR: l
glc
3
104.38 (d, C-1glc).
Decyl h-
D
-glucopyranoside monohydrate
-glucopyranoside (2e).—A
vol of 96% H SO (1.0 mL, 1.8 g, 18 mmol)
o
3
|(F )]. The refinement of 182 parameters
(1e ) and decyl i-
D
o
aq
with anisotropic temperature factors for all
2
4
non-hydrogen atoms converged at R/wR=
was added to decanol (252 mL, 209 g, 1.32
mol) in dioxane (400 mL). After raising the
−
1
2
0
.061/0.052 [w =| (F )]. The positions of
o
the hydrogen atoms had been calculated geo-
temperature to 80 °C,
D
-glucose (20.0 g, 111
metrically. The max/min residual electron
mmol) was added. The mixture was stirred for
6 h at 90 °C and then evaporated in vacuum
to about 3/4 of the original volume. After
heating for another 6 h, 2 M KOH (22 mL)
was added (pH 7.5 of the aq phase) and the
volatile components were evaporated first at
15 Torr followed by distillation at 0.01 Torr.
The residue (38 g) was filtered on 800 g silica
gel (9:1 EtOAc–EtOH). The resulting mixture
of 1e/2e (24.9 g, 70%, 7:3) was recrystallized
˚
−3
density was 0.34/−0.30 e A
Octyl h-
1c ) and octyl i-
.
D
-glucopyranoside monohydrate
(
D
-glucopyranoside (2c).—
D-
aq
Glucose (20.0 g, 111 mmol) was reacted with
octanol (172 mL, 142 g, 1.09 mol) in dioxane
(
400 mL) containing 96% H SO (1.0 mL, 1.8
2
4
g, 18 mmol), followed by neutralization and
evaporation of volatile compounds. The
residue was filtered through silica gel (9:1
EtOAc–EtOH): 21.88 g (67%) of 1c/2c (7:3).
The mixture was recrystallized twice from wa-
from a 5% solution in H O. The precipitate
2
was collected from the supernatant by cen-
trifugation (30 min, 9000 U) and dissolved in
hot water. After lyophilization, a mixture of
14.3 g of 1e/2e (9:1) was obtained. Additional
recrystallization from a 5% solution in water
ter to yield 8.99 g (26%) of octyl a- -glucopy-
D
ranoside monohydrate (1c ) as colorless small
aq
1
needles. H NMR: l 4.68 (d, 1 H, J 3.6 Hz,
1
3
H-1 ); C NMR: l 100.07 (d, C-1 ). The
glc
glc
supernatants (9.70 g), after chromatography
9:1 EtOAc–EtOH) and recrystallization, gave
provided 12.6 g (34%) decyl a- -glucopyra-
D
(
noside monohydrate (1e ) as small colorless
aq
additional 1.30 g (4%, H O) of 1c and 2.20 g
needles, containing 53% b anomer. Further
recrystallization for analysis as described
above provided the anomerically pure com-
2
aq
(
(
7%, acetone) of octyl b-
D
-glucopyranoside
1
2c), containing 5% 1c, as a white powder. H
13
1
NMR: l 4.17 (d, 1 H, J 7.3 Hz, H-1 ); C
pound. H NMR: l 4.66 (d, 1 H, J 3.6 Hz,
glc
1
3
NMR: l 104.31 (d, C-1glc).
H-1 ); C NMR: l 100.07 (d, C-1 ).
glc
glc
Nonyl h-
D
-glucopyranoside monohydrate
-glucopyranoside (2d).—
-Glucose (40.1 g, 223 mmol) was reacted
The aq supernatants were lyophilized (12.2
g, 1e/2e about 1:1) and chromatographed on
950 g of silica gel (9:1 EtOAc–EtOH); (a), (b)
and (c) were obtained:
(
D
1d ) and nonyl i-
D
aq
with nonanol (376 mL, 311 g, 2.16 mol) in
dioxane (800 mL) and p-toluene sulfonic acid
monohydrate (7.0 g, 37 mmol), followed by
neutralization and evaporation of volatile
compounds. The residue was filtered through
silica gel (9:1 EtOAc–EtOH): 40.67 g (60%) of
(a) 2.1 g of crude decyl a- -glucopyranoside
D
(a/b anomer 85:15). After recrystallization
from water, another 1.6 g (4%) of pure decyl
a-
D
-glucopyranoside monohydrate (1e ) was
aq
obtained.

V. Adasch et al. / Carbohydrate Research 314 (1998) 177–187
185
(
b) 3.5 g of crude decyl b-
D
-glucopyra-
acetone) of tetradecyl b-
D
-glucopyranoside
noside (a/b anomer 5:95). This mixture was
(2g), containing 55% 1g as a white powder.
recrystallized from 8 mL of acetone yielding
Hexyl 2,3,4,6-tetra-O-pi6aloyl-i-
ranoside and hexyl i- -glucopyranoside
D-glucopy-
2
.2 g (6%) of pure decyl b-
2e).
(
D-glucopyranoside
D
(
(2a).—To 360 mL of anhydrous Et O were
2
c) 4.4 g (12%) of anomer mixture of 1e/2e,
added: 27.0 g (47 mmol) 2,3,4,6-tetra-O-pival-
about 1:1.
oyl-a- -glucopyranosyl bromide [11], 6.2 mL
D
Dodecyl h-
D
-glucopyranoside (1f) and dode-
(5.1 g, 50 mmol) hexanol, 16.7 g (60.6 mmol)
Ag CO , and 75 g of fine powdered molecular
cyl i-
D
-glucopyranoside (2f).—
D-Glucose
2
3
˚
(
(
10.0 g, 56 mmol) was reacted with dodecanol
123 g, 0.66 mol) and dioxane (200 mL) con-
sieve (4 A). The mixture was stirred at room
temperature for 24 h, filtered and concen-
trated. The residue (35.3 g) was chro-
matographed on 1 kg silica gel (19:1
cyclohexane–EtOAc) to yield 23.07 g (80%) of
taining 96% H SO (0.5 mL, 0.9 g, 9 mmol),
2
4
followed by neutralization and evaporation of
volatile compounds. The residue was filtered
through silica gel (9:1 EtOAc–EtOH): 12.32 g
hexyl 2,3,4,6-tetra-O-pivaloyl-b-
D-glucopyra-
(
63%) 1f/2f (68:32). The a anomer was sepa-
rated by crystallization from EtOAc yielding
noside as a white powder: mp 74.3–75.0 °C;
2
3
[a] –8.69° (c 0.84, MeOH); R 0.38; IR (KBr):
D
f
−
1
1
5
(
1
1
.26 g (27%) of dodecyl a-
D-glucopyranoside
w 1745 cm (CꢀO); H NMR (CDCl ): l 0.85
3
1f) as colorless small platelets: mp (76.8)
(t, 3 H, J 7.0 Hz, H-6 ), 1.09, 1.13, 1.13, 1.20
alk
2
0
43.0–144.0 °C, lit 140–141 °C [9]; [a] +
(4 s, 36 H, CMe ), 1.20–1.35 (6 H, H-3 to
D
3
alk
01.0° (c 1.72, MeOH), lit+99.6° (c 1,
H-5 ), 1.43–1.60 (2 H, H-2 ), 3.42 (dt, 1 H,
alk
alk
1
MeOH) [9]; R 0.39; H NMR: l 4.66 (d, 1 H,
J 1a,1b 9.4, J 1a,2 6.9 Hz, H-1a ), 3.69 (ddd, 1
f
alk
13
J 3.6 Hz, H-1glc); C NMR: l 100.07 (d,
H, J 5,6a 1.7, J 5,6b 6.0, J 5,4 9.5 Hz, H-5 ), 3.80
glc
C-1 ). The supernatants (7.27 g), after chro-
(dt, 1 H, J 1b,2 6.6 Hz, H-1b ), 4.03 (dd, J
glc
alk
6b,6a
matography and recrystallization yielded addi-
12.0, 1 H, H-6b ), 4.19 (dd, 1 H, H-6a ),
glc
glc
tional 1.00 g (5%, EtOAc) of pure 1f and 1.90
4.33 (d, 1 H, J 1,2 7.9, H-1 ), 4.98 (dd, 1 H,
glc
g (10%, acetone) of pure dodecyl b-
D-glucopy-
J 2,3 9.5, H-2 ), 5.07 (t, 1 H, J =9.5 Hz,
glc
4,3
1
3
ranoside (2f) as a white powder.
H-4 ), 5.29 (t, 1 H, H-3 ); C NMR
glc
glc
Tetradecyl h-
D-glucopyranoside (1g) and te-
(CDCl ): l 14.1 (q, C-6 ), 22.6, 25.7, 31.6 (3
3
alk
tradecyl i- -glucopyranoside (2g).—
D
D-Glu-
t, C-3alk to C-5 ), 29.5 (t, C-2 ), 27.11,
alk
alk
cose (12.6 g, 70 mmol) was reacted with
tetradecanol (168.9 g, 0.79 mol) and p-toluene
sulfonic acid monohydrate (2.20 g, 11.6 mmol)
in dioxane (360 mL) for 6 h and after concen-
tration in vacuum (20 Torr) for an additional
27.14, 27.16, 27.21 (4 q, C(CH ) ), 38.76,
3
3
38.76, 38.81, 38.92 (4 s, CMe ), 62.2 (t, C-6 ),
3
glc
68.3 (d, C-4 ), 70.0 (t, C-1 ), 71.3 (d, C-2 ),
glc
alk
glc
72.3, 72.4 (2 d, C-3 , C-5 ), 101.1 (d, C-1 ),
glc
glc
glc
176.48, 176.53, 177.3, 178.1 (4 s, CꢀO). Anal.
1
8 h. Following neutralization and evapora-
Calcd for C H O : C, 63.97; H, 9.40.
3
2
56 10
tion of volatile compounds (0.001 Torr), the
residue was filtered on silica gel (9:1 EtOAc–
EtOH): 14.2 g (54%) of 1g/2g, (56:44). Recrys-
tallization from 1:1 EtOAc–EtOH yielded
Found: C, 63.98; H, 9.49.
The above prepared hexyl 2,3,4,6-tetra-O-
pivaloyl-b- -glucopyranoside (22.7 g, 37
D
mmol) was dissolved in 335 mL anhyd MeOH
containing 70 mmol NaOMe and kept at
room temperature for 24 h. After addition of
100 mL toluene, the solvent was evaporated
and the residue (15.8 g) was dissolved in 250
mL MeOH. The solution was stirred with
ion-exchange resin (20 g, Amberlyst 15) at
room temperature for 60 min, and then
filtered. The filtrate was concentrated in vac-
uum. The residue (8.89 g) was recrystallized
2
(
.93 g (11%) tetradecyl a-
D-glucopyranoside
1g) as a white powder, containing 52% b
2
D
0
anomer: mp (81–84) 144.0 °C; [a] +93.0° (c
1
1
.00, MeOH); R 0.40; H NMR: l 4.65 (d, 1
f
13
H, J 3.6 Hz, H-1 ); C NMR: l 100.00 (d,
glc
C-1 ). Anal. Calcd for C H O : C, 63.80; H,
glc
20 40
6
1
0.71. Found: C, 63.76; H, 10.54.
From supernatants (6.98 g), after chro-
matography (9:1 EtOAc–EtOH) and recrys-
tallization, was obtained 0.54 g (2%, 1:1
EtOAc–EtOH) of 1g and 1.35 g (5%, from
from 1:1 EtOAc–Et O yielding 7.72 g hexyl
2
b- -glucopyranoside (2a) (79% in the de-acy-
D

186
V. Adasch et al. / Carbohydrate Research 314 (1998) 177–187
1
lation step) as a white powder; H NMR: l
tradecyl b- -glucopyranoside (8.55 g, 11.8
D
13
4
.15 (d, 1 H, J 7.3 Hz, H-1 ); C NMR: l
mmol) and subsequent reaction with ion-ex-
change resin (Amberlyst 15) in MeOH yielded,
after recrystallization from acetone, 2.38 g of
glc
1
04.40 (d, C-1 ); CMC: 0.190 M.
glc
Decyl i- -glucopyranoside (2e).—Reaction
D
of decanol (3.40 g, 21.5 mmol) with 2,3,4,6-te-
tra-O-pivaloyl-a- -glucopyranosyl bromide
11] (12.4 g, 21.4 mmol) in Et O (120 mL) in
tetradecyl b-
D
-glucopyranoside (2g) (54% in
1
D
the de-acylation step) as a white powder. H
1
3
[
NMR: l 4.14 (d, 1 H, J 7.9 Hz, H-1glc); C
NMR: l 104.40 (d, C-1glc). Anal. Calcd
2
the presence of Ag CO (7.45 g, 27 mmol) and
molecular sieve yielded after silica gel chro-
matography (9:1 cyclohexane–EtOAc) 12.7 g
89%) of decyl 2,3,4,6-tetra-O-pivaloyl-b-
glucopyranoside as an oily product: R 0.62;
2
3
C H O : C, 63.80; H, 10.71. Found: C,
20 40
6
6
3.77; H, 10.51.
(
D
-
f
−
1
IR (CCl ): w 1745 cm
(CꢀO). Transesterifi-
-glucopyra-
Acknowledgements
4
cation of the acylated decyl b-
D
We are grateful to Dr Willfried Schramm
for valuable discussions.
noside (12.1 g, 18.1 mmol) with NaOCH /
3
MeOH and subsequent reaction with ion-ex-
change resin (Amberlyst 15) in water gave,
after lyophilization and recrystallization from
acetone, 4.20 g decyl b-
D
-glucopyranoside (2f)
References
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1
3
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glc
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D
-glucopyranoside (2f).—Reac-
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[
[
[
[
[
[
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(
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4
f
(
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(
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[
[
[
[
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(
(
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(
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action of tetradecanol (2.78 g, 13.0 mmol),
D
[
[
15] F. Nilsson, Inform, 7 (1996) 490–497.
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,3,4,6-tetra-O-pivaloyl-a- -glucopyranosyl
D
16] E. Barrall, B. Grant, M. Oxsen, E.T. Samulski, P.C.
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2
mL) in the presence of Ag CO (4.58 g, 17
2
3
[
[
[
17] D.L. Dorset, J.P. Rosenbusch, Chem. Phys. Lipids, 29
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(
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D
-glucopyranoside:
mp
−1
3
9.8–41.1 °C; R 0.65; IR (KBr): w 1748 cm
f
[20] V. Vill, T. Boecker, J. Thiem, F. Fischer, Liq. Cryst., 6
(
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[
(
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[
[
(
[
31] Tables of atomic co-ordinates, bond lengths, and bond
angles have been deposited with the Cambridge Crystal-
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Data Centre, 12 Union Road, Cambridge, CB2 1EZ,
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4
[
[
25] G.A. Jeffrey, Acc. Chem. Res., 19 (1986) 168–173.
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(
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[
[
6
115212 for 1a.
.