Microwave-assisted synthesis of alkyl glycosides

Article abstract of DOI:10.1081/SCC-100104035

The reaction of sugars with alcohols and catalytic amounts of an acid in a high frequency field (2.45 GHz) leads to high yields of the corresponding alkyl glycosides. The ratio of the α/β-anomers is influenced by the reaction conditions and reaction controlling.

Full text of DOI:10.1081/SCC-100104035

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MICROWAVE-ASSISTED
SYNTHESIS OF ALKYL
GLYCOSIDES
a
a
Matthias Nüchter , Bernd Ondruschka & Werner
b
Lautenschläger
a
Institut für Technische Chemie, Friedrich-
Schiller-Universitaät Jena , Lessingstraβe 12,
Jena, D-07743, Germany
b
Mikrowellen Labor Systeme (MLS) GmbH ,
Auenweg 37, Leutkirch/Allgäu, D-88299, Germany
Published online: 09 Nov 2006.
To cite this article: Matthias Nüchter , Bernd Ondruschka & Werner Lautenschläger
2001) MICROWAVE-ASSISTED SYNTHESIS OF ALKYL GLYCOSIDES, Synthetic
(
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 31:9, 1277-1283, DOI: 10.1081/SCC-100104035
To link to this article: http://dx.doi.org/10.1081/SCC-100104035
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SYNTHETIC COMMUNICATIONS, 31(9), 1277–1283 (2001)
MICROWAVE-ASSISTED SYNTHESIS OF
ALKYL GLYCOSIDES
1
,
1
Matthias Nu
and Werner Lautenschla
¨
chter, * Bernd Ondruschka,
2
¨
ger
1
Institut fu
¨
Friedrich-Schiller-Universita
¨
r Technische Chemie,
t Jena, Lessingstraße 12,
D-07743 Jena, Germany
Mikrowellen Labor Systeme (MLS) GmbH, Auenweg 37,
2
¨
D-88299 Leutkirch/Allgau, Germany
ABSTRACT
The reaction of sugars with alcohols and catalytic amounts of
an acid in a high frequency field (2.45 GHz) leads to high
yields of the corresponding alkyl glycosides. The ratio of the
a/b-anomers is influenced by the reaction conditions and reac-
tion controlling.
Alkyl glycosides with long-chain alkyl groups >C are important
8
nonionic tensides from natural raw materials. Up to now, the industrial
production of long-chain alkyl glycosides has been based exclusively on
1
,2
the Fischer glycosidation and has a production volume of 60 kt/year.
Alkyl glycosides are used more and more for the production of tenside
3
formulations because of their technological degradability. Furthermore,
alkyl glycosides play an important role as chemical intermediates in the
4
biotechnology (Scheme 1).
,5
*
Corresponding author.
1
277
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

¨
¨
NUCHTER, ONDRUSCHKA, AND LAUTENSCHLAGER
1
278
Scheme 1.
In the Fischer glycosidation of sugars with alcohols and catalytic
amounts of an acid, either the a-anomer alone or mixtures of a- and b-
anomers were obtained at the temperature range from 65 –140 C by long
ꢀ
ꢀ
6
reaction times (24–72 h). The a/b-ratio of alkyl glycosides is, as a rule,
without practical importance in normal tenside formulations, such as in
dishwashing detergents or in cosmetics. On the other hand, the application
characteristics of the b-anomers as more difficult available products, are
3
advantageous, especially in the microbiological research. According to
Fischer-glycosidation, b-anomers have been formed in a kinetically con-
trolled reaction. They react very fast under the reaction conditions to ther-
modynamically stable a-anomers.
7
The synthesis by Koenigs-Knorr as a competing process to the
Fischer glycosidation proceeds as a multistep reaction (acetylation–halo-
genation–substitution–deacetylation) and produces only b-anomers, but
this synthesis is economically and ecologically undesirable and has only
little laboratory importance (Scheme 2).
Scheme 2.

ALKYL GLYCOSIDES
1279
In the last years there have been many experiments conducted to intro-
duce dissipative-initiated (microwave-assited), low-temperature, synthesis
8
–15
reactions.
equipment. Most rections were carried out in domestic microwave ovens
The main failing was the absence of appropriate microwave
1
6,19
with insufficient control of temperature, energy, and pressure.
The
majority of results is poorly reproducible because of hetereogeneity of the
microwave fields in domestic microwave ovens. In this work, the Fischer
glycosidation was conveyed in a microwave oven ETHOS MR (MLS
¨
GmbH Leutkirch/Allgau) with installed refluxing apparatus and in a rotor
reactor with pressure bombs HPR 3000/1‘‘K’’. By means of these systems, a
scaling-up of microwave-assisted organic reactions to the kg-scale is poss-
ible, and the economic efficiency improves attractively, too. These micro-
1
8
wave set-ups were driven and controlled by a personal computer. The
pressure and temperature dependencies are quite reproducible. Moreover,
the microwave power is automatically recorded and the average microwave
power and the applied energy can be calculated. An example record of the
reaction of D-glucose with ethanol is represented in Figure 1.
In batch reactions, carbohydrates were converted in 50-g scale with
- 30-fold molar amount of alcohol in the presence of a catalytic amount
3
of acid (see Experimental). The results of the reactions of D-glucose,
D-mannose, and D-galactose with different alcohols are summarized in
Table 1 are found in all reactions; furanosides are not stable under the
reaction conditions.
Figure 1. Plot of temperature and pressure against time for the reaction of
D-glucose with ethanol in presence of catalytic amounts of HCl (ETHOS MR,
HPR 3000/1‘‘K’’).

¨
¨
NUCHTER, ONDRUSCHKA, AND LAUTENSCHLAGER
1
280
Table 1. Reaction of Sugars or Sugar Derivatives with Alcohols in a Microwave
Batch Reactor (Catalyst: HCl or Acetylchloride, 0.5 wt-%)
Yield [wt-%]
Alkyl-D-pyranoside
Sugar
Alcohol
Reaction Conditions
D-Glucose
Methanol
Methanol
Ethanol
Butanol
Butanol
Octanol
Octanol
Methanol
Ethanol
Methanol
Ethanol
Decanol
reflux, 60 min, 500/300 W
ꢀ
100%(a:b ¼ 85:15)
100%(a:b ¼ 100:0)
140 C, 20 min, 500 W
ꢀ
a
140 C, 30 min, 750 W, MSt
reflux, 40 min, 750 W
100%
a
90%
100%(a:b ¼ 95:5)
b
reflux, 60 min, 750 W, MeSt
ꢀ
c
120 C, 20 min, 500 W,
ꢀ
10%
95%
a
120 C, 20 min, 500 W, Mst
D-Mannose
D-Galactose
reflux, 35 min, 500 W
reflux, 40 min, 750 W
reflux, 35 min, 500 W
reflux, 40 min, 750 W
100%(a:b ¼ 100:0)
a
100%
100%(a:b ¼ 100:0)
a
100%
a
85%
ꢀ
Butyl-D-
glucose
Starch
120 C, 30 min, 500 W, Mst
ꢀ
ꢀ
Methanol
Methanol
140 C, 20 min, 500 W
140 C, 20 min, 500 W, Mst
60%(a:b ¼ 100:0)
100%(a:b ¼ 100:0)
Mst=magnetic stirring; MeSt=mechanical stirring of the reaction mixture,
a
b
mixture of anomers; three-fold amount of educts; 90% of D-glucose is degraded.
c
In further experiments the feasibility of the Fischer glycosidation was
tested in the microwave flow system. The premixed educts were pumped
1
9
through the reactor
under variation of residence time, pressure,
temperature, and microwave energy. The results of these tests are given in
Table 2.
EXPERIMENTAL
All educts were purchased from Sigma-Aldrich GmbH and used as
received. The melting points of the pure anomers were obtained on a Kofler
1
melting point apparatus and are uncorrected. H NMR spectra were
recorded on a Varian unity 400 or a Bruker 250 using HMDSO as standard
internal reference and D -ethanol or D -DMSO as a solvent. Analytical thin
layer chromatography was performed on Macherey & Nagel ALUGRAM
6
6
Õ
SIL G/UV254 silica gel plates by means of a mixture of acetone, methanol,
and absolute formic acid (30:1.5:1.5) as liquid phase. The reactions were
performed in commercial microwave systems (2,45 GHz) of MLS GmbH
¨
Leutkirch/Allgau – Germany. The equipments are characterised in Table 3.

ALKYL GLYCOSIDES
1281
Table 2. Reaction of D-Glucose or D-Glucose Derivatives with Alcohols in a
Microwave Flow Reactor (System: ETHOS, Catalyst: Acetylchloride, 0.5wt-%)
Reaction
Conditions
Residence Yield [wt-%]
Time (min) Alkyl-D-glucopyranoside
Sugar
Alcohol
ꢀ
ꢀ
ꢀ
D-Glucose Methanol 140 C, 16 bar
Methanol 140 C, 12 bar
10
4
5
100 a:b ¼ 95:5
100 a:b ¼ 10:90
a
Octanol
Octanol
120 C, 12 bar
120 C, 12 bar
95
100
ꢀ
a
Ethyl-D-
glucose
5
ꢀ
a
Butyl-D-
glucose
Octanol
120 C, 12 bar
5
100
ꢀ
b
Octanol
Decanol
120 C, 15 bar
110 C, 12 bar
12
5
100
100
ꢀ
a
Butyl-D-
glucose
a
b
Mixture of anomeres; The octyl-a-D-glucopyranoside is produced only.
Table 3. Characteristics of Microwave Systems Used
Microwave System
Reactor
Border Parameter
Õ
ETHOS MR
reflux apparatus
boiling point of the reaction
mixture normal pressure
ꢀ
HPR 3000/1, ‘‘K’’
HPR 1000/6
Glass reactor GR I
flow reactor
250 C, 30 bar, 250 mL
280 C, 80 bar, 6 ꢁ 50 mL
ꢀ
ꢀ
ꢀ
250 C, 3 bar, 500 mL
160 C, 50 bar, max 1.61/h
Õ
ETHOS ContFlow
Typical Experiment
D-Glucose 30 g (0.166 mol) is suspended in 200 g (4.76 mol) methanol.
Acetyl chloride (1 g) is added to this mixture, which is placed in a 250-mL,
three-necked, round-bottomed flask, equipped with Teflon-coated magnetic
stirring bar, fiber optical temperature sensor, and reflux condenser, and
Õ
installed in MW-system ETHOS MR. The magnetic stirrer bar is used
with 80% of the possible power. The mixture was irradiated with micro-
waves in the MW-system ETHOS MR for 60 min. After end of the reaction
(
TLC-control), the mixture of anomeres consisted of 85% methyl-a-D-glu-
copyranoside and 15% methyl-b-D-glucopyranoside (yield: 100%), and is
quenched, neutralized with 2 g magnesium oxide, and stirred for 30 min with
5 g carbon powder. The colorless mixture is filtrated, the surplus methanol is
distilled in vacuo, and resulting viscous oil is crystallized in a refrigerator.

¨
¨
NUCHTER, ONDRUSCHKA, AND LAUTENSCHLAGER
1
282
The anomer mixtures were analyzed as viscous oil. The solid product is
recrystallyzed from ethylacetate and the isolated yield of methyl-a-D-gluco-
pyranoside is 80%.
Higher surplus alcohols (octanol, decanol) are distilled in a steam
distillation. The reaction mixtures of the higher alcohols are analyzed as
anomeres mixtures. Solid residues are recrystallized from ethanol or ethy-
lacetate.
2
0,21
All products obtained are described in the literature
1
and were
confirmed by H NMR spectroscopy and finally by comparison (mp,
TLC) with authentic samples (Sigma-Aldrich GmbH).
ACKNOWLEDGMENTS
The authors gratefully acknowledge Dr. Kolar (Luckenwalde) for
discussions during the starting phase of this study.
REFERENCES AND NOTES
1
. Hill, K.; Rybinski, W.v.; Stoll, G. Alkyl Polyglycosides; VCH:
Weinheim, 1997.
2
3
4
5
6
7
8
9
. Rybinski, W.v.; Hill, K. Angew. Chem. Engl. Ed.; 1998, 37, 1328.
. Stubbs, G.W. Biochim. Biophys. Acta 1976, 426, 46.
. Fischer, E. Ber. Dtsch. Chem. Ges. 1893, 26, 40.
. Fischer, E. Ber. Dtsch. Chem. Ges. 1895, 28, 1145.
. Kahre, J.; Nieendick, C. Verfahrenstechnik 1995, 29, 35.
. Koenigs, W.; Knorr, E. Ber. Dtsch. Chem. Ges. 1901, 34, 957.
. Gedye, R.N.; Smith, F.E.; Westaway K. C. Can. J. Chem. 1988, 66, 17.
. Abramovitch, R.A. Org. Prep. Proc. Int. 1991, 23, 685.
1
1
1
1
0. Caddick, S. Tetrahedron 1995, 51, 10403.
1. Strauss, C.R.; Trainor, R.W. Aust. J. Chem. 1995, 48, 1665.
2. Galema, S.A. Chem. Soc. Rev. 1997, 26, 233.
3. For reactions of carbohydrates under focused microwaves see: Gelo-
Pucic, M.; Guibe-Jampel, E.; Loupy, A.; Trincone, A. J. Chem. Soc.,
Perkin Trans. 1 1997, 1001.
1
4. Limousin, C.; Clephax, J.; Loupy, A.; Petit, A. Tetrahedron 1998, 54,
1
3567.
5. Gelo-Pucic, M.; Guibe-Jampel, E.; Loupy, A.; Galema, S.A.; Mathe,
D. J. Chem. Soc., Perkin Trans. 1 1996, 2777.
1
1
1
6. Srikrishna, A.; Nagaraju, S.; Kondaiah, P. Tetrahedron 1995, 51, 1809.
7. Diaz-Ortiz, A.; Prieto, P.; Vazquez, E. Synlett. 1997, 269.

ALKYL GLYCOSIDES
1283
Õ
1
1
2
2
8. The microwave apparatus as controlled by PC (Easywave designed by
MLS).
9. A membran pump of ALLDOS Eichler GmbH, Pfinztal, Germany,
type 281-9.6 V63/G02 was used.
0. For alkyl-a-glucopyranosides see: Brown, G.M.; Dubreuil, P.;
Ichhaporia, F.M.; Desnoyers, J.E. Can. J. Chem. 1970, 48, 2526.
1. For alkyl-b-glucopyranosides see also (5) and Bollenbach, G.N.
Methyl Glycoside; Academic Press: New York, 1958.
Received in the Netherlands July 7, 2000