M. Ibert et al. / Carbohydrate Research 346 (2011) 512–518
517
monosaccharides, through benzilic rearrangement. The proposed
1.3.3. Triacid synthesis from the oxidation of
D-glucaric acid
mechanism accounts for the formation of all diastereoisomers in
different monosaccharides series, along with the stereochemistry
of the resulting compounds. GC analyses combined with NMR
studies of the reaction mixtures established unambiguously the
configuration of the stereogenic centers of the generated triacids.
Sodium -glucarate (23.2 g, 81.2 mmol) and TEMPO (0.3 g,
D
2 mmol) in water (3.3 L, 2 Mohm cm) were electrolyzed at pH
12.2 (adjustment with aqueous KOH 4 mol LÀ1) at 5 °C with a
1000 mA intensity (190 cm2 graphite felt anode without faradic ex-
cess). A mixture containing D-glucaric acid (47%) and triacid acid
(22%) as their potassium salts was obtained together with 27% of
degradation side-products.
1. Experimental
1.3.4. Oxidation of 13C enriched
D-glucose
1.1. Classical electrolysis reactor
13C enriched glucose (100 mg), TEMPO (50 mg), and Na2CO3
(500 mg) in water (80 mL) were electrolyzed at a temperature of
5 °C with a 200 mA intensity (20% Faradic excess), to yield a mix-
A control and an electrolysis device composed the reactor,
which allowed a tight pH and temperature control during the elec-
trolysis. A Micro-pump N21 (from Ismatec) allowed the circulation
between the two parts and was calibrated to a flow rate of
80 mL minÀ1. The temperature was controlled using a jacketed
reactor equipped with a cryothermostat Ecoline RE107 from Lauda.
The power generator was a SDL/PA-R from Sodilec. The pH was
controlled by an Inlab 413 glass electrode connected to an auto-
mated ORSO Electronic System from Logilap™. The electrolysis
time was programmed using a OTIO 93000-001 timer.28
ture containing at least 90% of D-glucaric acid after work-up.
1.4. Purification of the triacid fraction
Purification of triacid was achieved in three steps: Concentra-
tion of the oxidation mixture and acidification to pH 8 afforded a
mixture of the crude potassium salts of the different acids. Most
of the D-glucaric acid was further removed by precipitation of its
mono potassium salt by adjusting the pH to 3.8 by careful addition
of a strong acid exchange H resin CA200. The mother-liquor (65%
enriched in triacid) was subsequently passed over a cationic ex-
change column (PCR532H+) eluted with water. The aqueous phase
was dried in vacuo, to afford a diastereoisomeric mixture of triacid
acid in a 8:2 ratio with a purity of 96% by GC.
1.2. Large scale Priam electrolysis reactor
Larger scale oxidations were achieved on a PRIAM 1-2C reactor
of 3300 mL capacity, fitted with a graphite felt anode and two
stainless steel cathodes, both anode and cathodes having
a
190 cm2 area and 5 mm thickness. A centrifugal pump MD-10-
230GS01 (from Iwaki) allowed the circulation of the electrolyte be-
tween electrolysis and control devices with a calibrated flow rate
of 11 L minÀ1. Temperature, pH, and reaction time were controlled
as for the classical electrolysis reactor.28
1.5. Analytical analyses
All the GC analyses that were performed on the reaction mix-
tures were performed according to the procedure previously de-
scribed by Ibert et al.5 All 1H NMR and 13C NMR spectra were
recorded on a Bruker 300 MHz spectrometer in D2O and the proton
spectra referenced to the residual H2O peak at 4.79 ppm.
1.3. Oxidation general procedure7
D
-Glucose (0.02 mol), TEMPO (0.5 mmol), and NaBr (0.02 mol,
when needed) in water (MiliQ, 330 mL, 2 MohmÁcm) were electro-
lyzed at the desired scan rate with 20% faradic excess. Two elec-
trodes composed the electrolysis system: a graphite felt anode
(90 cm2) and a stainless steel cathode (50 cm2). The amount of cur-
rent needed was calculated as the following: two electrons were
required for the oxidation of the hemiacetal function, and four
electrons for the primary alcohol function, topped with 20% excess
of the oxidant to assure completion. At the end of the oxidation,
the reaction was concentrated to 100 mL, under vacuum. The pH
was adjusted to 8 by addition of Amberlyst resin (CA200, H+). After
removal of the resin by filtration, the remaining solvent was evap-
orated under vacuum, and the resulting product was dried under
vacuum at 60 °C for 24 h.
Acknowledgments
We thank the Roquette Frères society and the Agence Nationale
de la Recherche Technologique for financial support of Mathias
Ibert, as well as the CNRS and the National Institute for Applied Sci-
ences of Rouen (INSA de Rouen) and the University of Rouen for the
scientific and technical environment. Nabyl Merbouh would like to
thank the Consulate-General of France in Vancouver for the travel
support during the course of this research.
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D
-glucose and sodium
D-gluconate
D
-Glucose (15 g, 75.8 mmol), sodium
D-gluconate (8.5 g,
39 mmol) and TEMPO (0.3 g, 2 mmol) in water (3.3 L, 2 Mohm cm)
were electrolyzed at pH 12.2 (adjustment with aqueous KOH
4 mol LÀ1) at 5 °C with a 1000 mA intensity (190 cm2 graphite felt
anode—20% Faradic excess). A mixture containing D-gluconic acid
(4%), glucaric acid (70%), and triacid acid (22%) as their potassium
salts was obtained together with 4% degradation side-products.