Synthesis of α- and β-glucose pentaacetates
Vaardigheden, Hogeschool Utrecht
Wouter Nieuwstraten, w_oute_r@hotmail.com
Abstract
Two glucose pentaacetate anomers are synthesized using two separate catalysts and acetic anhydride with
glucose. Iodine and sodium respectively yield α- and β-glucose pentaacetate.
5Results and discussion
Glucose exists in equilibrium of two different
anomers; α- and β-glucose. The difference
between these two stereo isomers is the location
of the hydroxyl group on the C1-atom. This
10equilibrium is pH dependant and described in
Scheme 1.
According to the citations used, the α-glucose is
formed in acidic solution, while the β-glucose is
formed in basic solution. In neutral pH, the
15glucose prefers to be in the β-state. This state
has less hindrance since all hydroxyl groups are
in equatorial position. In the α-state, the C1-hy-
droxyl exists in axial position, which is less fa-
vorable due to some steric hindrance from the
20C2-hydroxyl.
Scheme 1: Acid-Base equilibrium of α- and β-glucose
anomers
The different anomers form because of anomer-
25ization; the hemiacetal bond (C1) breaks open to
form the aldehyde (and alcohol). The aldehyde
will close the ring to form the hemiacetal again.
Depending on the conditions, the hydroxyl
group on the hemiacetal will form the α- or β-
30anomer.
When glucose is reacted with acetic anhydride
and a catalyst the pentaacetate forms. Depend-
ing on the type of catalyst used in the reaction,
either α- or β-glucose pentaacetate is synthes-
35ized. The acetic anhydride reacts with the hy-
droxyl groups in a general ester reaction
(Scheme 2).
Date: 2009-03-05
Scheme 2: Mechanism of esterification with acetic anhyd-
40ride
Hypothesized is that the sodium acetate in the
reaction mixture will not change the pH drastic-
ally, but will buffer the acetic acid co-product
enough to prevent formation of the α-anomer.
45The iodine has no buffering properties; the
solution will become acidic, consequently the
α-anomer will form.
When the hemiacetal is formed into the more
stable acetal (hydroxyl group is converted to an
50ester/ether), the anomerization will not occur
anymore. Therefore the pentaacetate glucose
anomers created can be isolated and tested for
their properties.
In total three experiments were performed, of
55which one experiment was performed with
galactose in stead of glucose. The galactose
pentaacetate could not be isolated.
The found data on all products are displayed in
Table 1. To view the experiment description,
60see the Experimental section.
Table 1: Physical data and constants, all reactions per-
formed with acetic anhydride.
Reagents Product data
Catalyst Sugar Yield Appearance Mp. α/ β
NaOAc D-Glucose 68% White solid 130°C β
I2 D-Glucose 87% White ndls. 91°C α
I2 D-Galactose No isolatable product formed
The anomers are determined by comparing the
1
H-NMR spectra of the products; according to
65the given literature, the resonance peak at 6.6
ppm for the β-anomer (Figure 1) is shifted to
7.3 ppm for the α-anomer (Figure 2).
The IR spectra should be nearly exactly the
same for both products. However, the α-
Page 1 of 3
 70anomer’s IR spectrum has a distinctive hydro-
gen bridge peak at around 3200. This may be
caused by some trapped methanol/water in the
crystalline structure of the product. It may also
be caused by some residing hydroxyl peaks, but
75these should have been washed away from the
product.
The melting point (mp.) found unexpected
properties in the α-anomer. Instead of a melting
point of 110 °C (Literature ), a melting point of
8091 °C was found. This may correspond to the
IR spectrum found earlier, as impurities may
(will) lower melting points. In the β-anomer, no
abnormalities have been discovered; a melting
point of 130 °C was obtained, while 130-131
85°C was discussed in the synthesis in Literature .
Synthesis of α-D-galactose pentaacetate
10 mL of acetic anhydride is added. 2 g of D-
115galactose is carefully added. While stirring with
a magnetic stirrer, add few crystals (max. 0.5 g)
of iodine.
Keep this mixture at room temperature while
stirring for at least 40 minutes. When the reac-
120tion has proceeded, a solution of 10% sodium
bisulfite is added until the solution’s color turns
to pale lemon yellow.
The remaining solution is mixed with approx-
imately 50 g of ice and is stirred until all ice is
125dissolved. The powder is then filtered off. The
filtered product is recrystallized from a 1:2
solution of water/methanol.

Experimental Literature
1. Blokboek VC6R 2008-2009, Vaardig-
Synthesis of α-D-glucose pentaacetate 130 heden, C. Schneiders, p. 15-17
To a 50 mL round bottomed flask, 10 mL of
acetic anhydride is added. 2 g of D-glucose is
90carefully added. While stirring with a magnetic
stirrer, add few crystals (max. 0.5 g) of iodine.
Keep this mixture at room temperature while
stirring for at least 40 minutes. When the reac-
tion has proceeded, a solution of 10% sodium
95bisulfite is added until the solution’s color turns
to pale lemon yellow.
The remaining solution is mixed with approx-
imately 50 g of ice and is stirred until all ice is
dissolved. The powder is then filtered off. The
100filtered product is recrystallized from a 1:2
solution of water/methanol.

Synthesis of β-D-glucose pentaacetate

To a 50 mL round bottomed flask, 2.5 g of D-
glucose and 2 g of sodium acetate is added. Add
10512.5 mL acetic anhydride and apply cooler to
flask. Heat the mixture to 100°C for 1.5 hours
while stirring.
After the reaction, mix the solution with 125
mL of ice water (0°C!). Keep mixing at 0°C for
110another 10 minutes. Filter off the product and
recrystallized from a 1:2 solution of
water/methanol.

Page 2 of 3
 Appendix

Figure 4: IR of the pentaacetate formed with

iodine as the catalyst.

Figure 1: 1H-NMR of the pentaacetate in CDCl3 formed

with sodium acetate. The anomer formed is the β-anomer.

135
Figure 2: 1H-NMR of the pentaacetate in CDCl3 formed
with iodine as catalyst. The anomer formed is the α
-anomer.

140Figure 3: IR of the pentaacetate formed with sodium acet-

ate.

5 Page 3 of 3