Micellar effect on the direct Fischer synthesis of alkyl glucosides

Article abstract of DOI:10.1016/j.apcata.2017.04.002

This manuscript presents results from the investigation on the synthesis of alkyl glucosides by the novel, very efficient and environmentally friendly protocol of the Fischer-type synthesis from unprotected glucose and aliphatic alcohols. The use of the dual functionality catalysts (surfactant?+?acid catalyst) and micellar reaction system are the main novelty of described method. It has been found, that in developed method of synthesis the reaction of unprotected glucose with aliphatic alcohols carried out with significantly different route, than the normal (classical) route and leads to alkyl glucopyranoside derivatives with high yields. In progress analyses by DLS, HPLC and GC/MS confirm the general postulated pathway of developed method.

Full text of DOI:10.1016/j.apcata.2017.04.002

Applied Catalysis A, General 539 (2017) 13–18
Contents lists available at ScienceDirect
Applied Catalysis A, General
journal homepage: www.elsevier.com/locate/apcata
Research Paper
Micellar effect on the direct Fischer synthesis of alkyl glucosides
J. Nowicki⁎, J. Woch, M. Mościpan, E. Nowakowska-Bogdan
Institute of Heavy Organic Synthesis “Blachownia”, PL47-225 Kędzierzyn-Koźle, Poland
A R T I C L E I N F O
A B S T R A C T
Keywords:
This manuscript presents results from the investigation on the synthesis of alkyl glucosides by the novel, very
efficient and environmentally friendly protocol of the Fischer-type synthesis from unprotected glucose and
aliphatic alcohols. The use of the dual functionality catalysts (surfactant + acid catalyst) and micellar reaction
system are the main novelty of described method. It has been found, that in developed method of synthesis the
reaction of unprotected glucose with aliphatic alcohols carried out with significantly different route, than the
normal (classical) route and leads to alkyl glucopyranoside derivatives with high yields. In progress analyses by
DLS, HPLC and GC/MS confirm the general postulated pathway of developed method.
Alkyl glucoside
Fischer reaction
Catalysis
Micellar effect
1. Introduction
not removed from the reaction mixture by conventional methods, but is
captured inside the micelles. This phenomenon is the main essence of
Alkyl glucosides (AGs) are considered as a very important class of
biodegradable nonionic surfactants. AGs contain a carbohydrate head
group (glucose, galactose, maltose, xylose etc.) and hydrocarbon tail
(usually a linear alkyl chain of different length) [1–5]. AGs have
numerous important applications as a main components of personal
care products, cosmetics, in the preparation of microemulsions (espe-
cially in detergents and pesticide formulations) because of their
excellent behavior at interfaces and also as agents for extraction of
organic dyes and in the membrane protein research [6–8]. The common
method of the synthesis of alkyl glucosides is Fischer glycosylation
through direct or transacetalization route. In the direct synthesis (one-
step protocol), fatty alcohol reacts with glucose or commercial glucose
oligomers (e.g. glucose syrup, starch) producing a complex mixture of
AGs with various degree of oligomerization (n ≥ 1, Scheme 1) [9,10].
The main disadvantage of this procedure, however, is poor solubi-
lity of carbohydrates in long chain aliphatic alcohols. One of the
possible way to eliminate this inconvenience is to conduct this process
in biphasic reaction system with phase transfer catalyst (ptc), such as
ammonium salts or ammonium ionic liquids [11–15]. A special case of
biphasic catalysis is the synthesis in micellar reaction systems [16–18].
Formation of micelles results in a great increase in interfacial surface of
two immiscible phases, which makes the reaction proceeding at the
interface more effective. Synthesis in micellar reaction systems, such as
microemulsion is nowadays one of the most interesting and promising
method applied in organic synthesis [19,20]. One of the most specta-
cular example described in literature of “micellar” effect is esterifica-
tion reactions [21–23]. Water formed during esterification reaction is
this method. Synthesis in biphasic systems has been also applied in
carbohydrate chemistry, in particular in enzymatic methods of the
synthesis of alkyl glucosides. Water in oil microemulsions with reverse
micelles provide an interesting alternative to common organic solvents
in enzyme catalysis with strong hydrophilic substrates, such as carbo-
hydrates. Several examples of the synthesis of alkyl glycosides in
reverse micelles using glycosidases as enzyme catalysts were reported
with satisfying results compared to standard aqueous reaction media
[24–29].
The use of micelles for separation of reactants was first described by
Kobayashi in esterification of carboxylic acids and alcohols [22]. The
surfactant-type acid catalyst (dodecylbenzenesulfonic acid, DBSA) and
organic substrates in water form microdroplets with hydrophobic
interior. For lipophilic substrates (carboxylic acids and alcohols), the
equilibrium position between the substrates and the products (esters)
lies at the ester side and water molecules would be moved out of the
droplets due to hydrophobic nature of their interior.
Application of interfacial phenomena in synthesis of alkyl gluco-
sides is very limited. Only a few reports in this field described the use of
micellar reaction systems, but not in the synthesis of alkyl glucosides
directly from the unprotected glucose. Although Kobayashi et al.
reported stereoselective C-glycosylation in water in microemulsion
reaction system with the use of DBSA as a surfactant catalyst, but in
this method only fully protected (acetylated) sugars were used [30].
Direct synthesis of alkyl glucosides from peracetylated 1-bromoglucose
and aliphatic derivatives of phenols was also described by Kumar [31].
The reaction was carried out in the presence of surfactant ionic liquids,
⁎
Corresponding author.
E-mail address: nowicki.j@icso.com.pl (J. Nowicki).
http://dx.doi.org/10.1016/j.apcata.2017.04.002
Received 3 February 2017; Received in revised form 29 March 2017; Accepted 2 April 2017
Available online 04 April 2017
0926-860X/ © 2017 Published by Elsevier B.V.

J. Nowicki et al.
Applied Catalysis A, General 539 (2017) 13–18
min N2) and methanol/water was used as the mobile phase (0.5 ml/min
flow rate). Data were collected and processed using CHROMELEON
(version 6.80) software. Analyses were performed at 30 °C and chro-
matograms of synthesized alkyl glucosides are presented in Fig. S1–S3
(Supporting information).
Scheme 1. Synthesis of alkyl glucoside, “classic” route.
GC/MS analyses were carried out on the head-space system using
HP 5890 Series II chromatograph equipped with flame ionization
which play a dual role both as simple phase transfer catalyst and
solvent.
detector,
capillary
column,
Ultra-high-2
(5HT), l = 15 m,
d = 0,32 mm. All samples were transformed into silane derivatives
with BSA (N,O-bis(trimethylsilyl)acetamide). Instrument settings: in-
jector temp. −360 °C, detector temp. − 380 °C. Temperature program-
ming: initial isotherm 100 °C – 1 min, 100–380 °C – gradient 15 °C/
min., final isotherm 380 °C − 3 min. Carrier gas: argon −1.8 ml/min.
GC/MS chromatograms and corresponding MS spectra are presented in
Figs. S4–S13 (Supporting information).
Dynamic Light Scattering (DLS) analyses were performed with
Zetasizer Nano ZS (Malvern) equipped with vertically polarized in-
cident light of wavelength = 633 nm, supplied by a He-Ne laser.
Measurements were carried out at angle 173° at 25 or 50 °C. The
apparent hydrodynamic diameter of aggregates formed in studied
materials, Dh, was calculated using the Stokes-Einstein equation from
data derived by cumulants analysis and was given as average from 4
measurements. All samples were filtered before measurements through
Pureland PVDF syringe filters of the nominal pore size 0.22 μm. Size
distributions of micelles for synthesized alkyl glucosides are presented
in Fig. S14 and in Table S1 (Supporting information).
Fischer glycosidation may be considered as a very similar to
esterification reaction (acidic catalyst and water as a main by-product).
Our idea was based on the methodology successfully applied in the
esterification reaction. In contrary to the above described esterification
reaction, both reagents (glucose) and products (alkyl glucoside, water)
have strong hydrophilic nature. This could suggest, that it will be
difficult to remove water from the reaction mixture. Our study,
however, clearly showed, that it could be done. We demonstrated, that
Fischer glycosidation reaction in micellar system may be carried out
according to similar methodology, after some modification.
This paper presents investigation of the synthesis of alkyl glycosides
direct from glucose and aliphatic alcohols in microemulsion reaction
system. The use of micellar reaction system in the synthesis of alkyl
glucosides from alcohols and unprotected glucose has been described
for the first time. The proposed reaction pathway is presented below
(Scheme 2).
2. Experimental
3. Results and discussion
2.1. Materials
3.1. Synthesis of alkyl glucosides
D-glucose (Sigma-Aldrich), 1-octanol, 1-decanol and 1-dodecanol
(Alfa Aesar), dodecylbenzenesulfonic acid (DBSA) 95% (Sigma-
Aldrich), methanesulfonic acid 99% (Sigma-Aldrich) and octyl-β-glu-
copyranoside (Sigma-Aldrich) were used as received. Glucopon 225 DK
(C8-C10 alkyl polyglucoside, BASF) was used as commercial alkyl
glucoside surfactant for comparative synthesis.
To demonstrate our assumptions reactions of D-glucose with
selected aliphatic alcohols have been conducted under biphasic (mi-
cellar) reaction conditions in the presence of dodecybenzenesulfonic
acid (DBSA) as surfactant catalyst (Table 1). It has been examined in
terms of alcohol used, effect on additional amount of water and reaction
temperature. The results clearly demonstrate, that DBSA effectively
catalysed this reaction. Firstly, the reaction of glucose with 1-octanol
(the molar ratio of glucose to alcohol = 1:10) has been investigated in
the presence of dodecylbenzenesulfonic acid (5 mol% in relation to
glucose) as surfactant-type Brønsted acid for 24 h at 60 °C, 70 °C and
80 °C, with addition of water (10 wt% in relation to glucose). In the
presence of water the conversion of glucose (determined by HPLC
analysis) decreased from 96.1% at 60 °C to 55.2% at 80 °C (Table 1,
entries 1–3). It has been observed, that increasing reaction temperature
had a negative impact on glucose conversion. In the absence of
additional amounts of water the situation has significantly changed.
At 60 °C conversion of glucose was 79.7%, but after increasing the
temperature to 80 °C conversion was also increased and reached 99%.
2.2. Synthesis procedure
A typical reaction was carried out by adding 3.6 g (0.02 mol)
glucose to a 100 ml glass reactor containing 0.2 mol of corresponding
alcohol and 0.33 g (0.01 mol) dodecylbenzenesulfonic acid. The result-
ing suspension was agitated intensively (700 rpm) at desired tempera-
ture for 24 h. After that the reaction mixture (clear liquid) was cooled
down to room temperature and analysed (GPC and GC/MS).
2.3. Analytical methods
High performance liquid chromatography (HPLC) analyses were
carried out on Dionex UltiMate 3000 chromatograph (Thermo Fisher
Sci.) and RP-18 Purospher HPLC column 250 × 4.6 mm, 5 μm. The
system was fitted with ELSD 2000 UV detector (Alltech, 50 °C, 1.5 ml/
Table 1
Results of Fischer synthesis of alkyl glucosides in presence of surfactant- type Brønsted
catalysts.
Entry
Alcohol
Catalyst
Reaction temp.
°C
Water
wt%
Conversion
%
1
2
3
4
5
6
7
8
9
1-octanol
1-octanol
1-octanol
1-octanol
1-octanol
1-octanol
1-decanol
1-dodecanol
1-octanol
DBSA
DBSA
DBSA
DBSA
DBSA
DBSA
DBSA
DBSA
60
70
80
60
70
80
80
80
80
10
10
10
–
–
–
–
–
–
96.1
66,3
55.2
79.7
80.5
99
98.2
97.5
45.7
APG + KMS
(reaction conditions: glucose: alcohol molar ratio − 1:10; DBSA − 5 mol%; 24hr;
Scheme 2. Synthesis of alkyl glucosides, “microemulsion” route.
700 rpm).
14

J. Nowicki et al.
Applied Catalysis A, General 539 (2017) 13–18
Table 2
Effect of amount of added catalyst on glucose conversion.
Entry
Alcohol
Reaction temp °C
DBAS
mol%
Conversion
%
9
10
11
1-octanol
1-octanol
1-octanol
80
80
80
5
2.5
1
99.0
96.4
67.1
(reaction conditions: glucose: alcohol molar ratio − 1:10.
Fig. 3. HPLC chromatogram of Oct-G sample (entry 6).
3.2. Micellar effect in Fischer synthesis of alkyl glucosides—general
assumption
As shown before, the satisfactory conversions of glucose (96–99%)
were achieved in experiments with the amounts of catalyst (DBSA) at
the level 2.5–5 mol%. Because of the hydrophobicity of continuous
phase (octanol) and hydrophilicity of cluster interior in dispersed
phase, water molecules could be gradually trapped in the cluster
interior while the product (alkyl glucoside) enters the continuous
phase. With the progress of the reaction, surfactant clusters are
enlarged to form inverse micelles with the aid of alcohol as a co-
surfactant (Figs. 1 and 2).
This mechanism was also observed in similar solvent-less esterifica-
tion carried out in micellar system [23]. Synthesis of alkyl glucosides in
micellar reaction system in the presence of surfactant catalysts is more
complex than conventional method. In the reaction mixture are present
both surfactant catalyst (DBSA) and alkyl glucoside. Alkyl glucosides
Fig. 1. Cluster effect of water capture.
(Table 1, entries 4–6). The same reaction conditions, using 1-dodecanol
instead 1-decanol resulted with similar conversions (Table 1, entries
7–8).
The effect of the amount of the added catalyst (DBSA) on the
conversion of D-glucose has been also investigated. Table 2 shows the
lower conversion of glucose for low load of DBAS (only 67% for 1 mol
%) and the best result for 5 mol% of added catalyst.
Fig. 2. Proposed micelle structure.
15

J. Nowicki et al.
Applied Catalysis A, General 539 (2017) 13–18
Fig. 4. GC chromatogram of Oct-G sample (a, entry 6) and octyl-β-glucopyranoside (b).
acid, 0.2 g) were used (Table 1, enter 9). As can be seen the presence of
APG and homogeneous sulfonic acid were not sufficient to obtain high
yield of alkyl glucoside. Conversion of glucose was only 67%. One of
the possible explanations of this phenomenon is the different solubility
of used reagents and formed products. Water is fully miscible with APG
and does not form micelles able to capture water molecules.
3.3. Micellar effects on Fischer synthesis of alkyl glucosides—effect on
selectivity
Fig. 3 presents HPLC chromatogram of reaction product of glucose
and 1-octanol (Oct-G). As can be observed in Fig. 3, the reaction of
glucose with 1-octanol in micellar reaction system leads to product
contains octyl glucoside and small amount of octyl diglucoside. The
presence of main product was confirmed by HPLC chromatography and
CG/MS spectroscopy using octyl-β-D-glucopyranoside and D-glucose as
analytical standards. GC/MS chromatograms of Oct-G sample (a) and
octyl-β-D-glucopyranoside (b) are presented in Fig. 4. Surprisingly, it
has been found, that on the GC chromatogram only two main
compounds were seen (no α and β anomers of octylglucofuranoside
present). The results of GC/MS analysis confirmed, that the product was
a mixture of α and β anomers of octylglucopyranoside 1. GC/MS
analysis also shows the specific selectivity of developed method. In the
reaction mixture α and β anomers of octylglucofuranoside 2 (generally
observed in post-synthesis mixtures obtained in Fischer glycosidation
conducted in conventional reaction conditions) were not seen (Scheme
3) [32]. Table 3 presents α and β anomers ratios for selected alkyl
glucosides.
Scheme 3. Possible change of selectivity in “micellar” Fischer reaction.
Table 3
α and β anomer ratios for selected alkyl glucosides.
alkyl glucoside
Yield, %
anomer α, wt%
anomer β, wt%
Oct-G
Dec-G
Laur-G
99.0
98.6
97.4
60.4
63.8
67.7
39.6
36.2
32.3
are characterized by very good surfactant properties and may affect the
course of the reaction. However, medium chain alkyl glucosides
(e.g. C8) are characterized rather by foaming than emulsifier properties.
In order to verify the possible impact of APG, the simulated experiment
has been done. In place of surfactant catalyst commercial APG
(Glucopon, 0.4 g) and homogeneous acid catalyst (methanesulfonic
As can be seen from Table 3, the dominant anomer is octyl-α-
16

J. Nowicki et al.
Applied Catalysis A, General 539 (2017) 13–18
Fig. 5. Micelle hydrodynamic diameters.
glucopyranoside, which is the main component in reaction product of 1-
octanol and glucose according well described Fischer glycosylation
mechanism [9].
For C10 and C12 alcohols in post-synthesis mixtures only single
products: corresponding alkyl glucosides were observed. The results of
HPLC and GC/MS analysis of all glucosides have been shown in
Supporting Information file.
aliphatic alcohols. Dodecylbenzenesulfonic acid has shown dual cap-
abilities, both as surfactant and Brønsted catalyst in Fischer glycosida-
tion reaction. Dodecylbenzenesulfonic acid is also considered as
environmentally acceptable catalyst. Sodium salt of DBSA formed after
alkali working out is fast and fully biodegradable. The main originality
and novelty of the described protocol is related to creating microemul-
sion reaction system for effective course of reaction. The described
method has additional advantages compared to the classical method of
Fischer. First of all at the lower reaction temperature high carbohydrate
conversion is achieved. Furthermore the reaction does not result in
oligomers of alkyl glucoside formation. The process also does not
require the removal of water using distillation methods, which gen-
erally requires a vacuum equipment. The described method may have
significant application potential, especially in synthesis of series of
important carbohydrate surfactants—alkyl glucosides.
3.4. Micellar effect in Fischer synthesis of alkyl glucosides—formation of
micelles
The key pathway assumption for the research described in this
paper was to create a micellar system for the Fischer reaction. The
reaction products were clear liquids. It is well known that the solubility
of water and carbohydrates (e.g. glucose) in C8–C12 alcohols is very
low. HPLC analyses and GC/MS showed a virtual absence of glucose in
post-synthesis mixtures. Described in Scheme 2 path of the reaction
assumed, that the water molecules, a main byproduct of the Fischer
reaction were captured inside the surfactant micelles. To confirm this
assumption, the micelle size was measured by DLS method (Fig. 5).
For C8–C12 alkanols micelle hydrodynamic diameter was in the
range of 6.5-40.9 nm and could be classified as micromicelles. Analyses
of dynamic light scattering results indicated Dh = 6.5 nm (C8 alcohol),
Dh = 6.7 nm (C10 alcohol) and Dh = 40.9 nm (C12 alcohol). 1-
Dodecanol is solid in 25 °C, so size measurements must be carried out
in 50 °C. Hydrodynamic diameter of microemulsion droplets, where the
continuous phase is 1-dodecanol was, therefore, significantly larger
(40.9 nm) than for the 1-octanol and 1-decanol (6.5 and 6.7 nm,
respectively). This is consistent with the published literature data.
Microemulsion droplet size grows with increasing temperature is
common [33,34]. Calculated polydispersity indexes (Pdi) were 0.3 for
C8 − C10 glucosides, which are characteristic for moderate type
polydispersity. For C12 glucoside Pdi = 0.6, which is characteristic for
broad type polydispersity.
Acknowledgements
The research was conducted with financial support from the Polish
Ministry of Science and Higher Education for statutory research. This
work has been also done within the framework of COST Actions
MP1106 “Smart and green interfaces − from single bubbles and drops
to industrial, environmental and biomedical applications (SGI)”
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