WO2008034990A1 - Method for preparing a composition of glucuronic acid or a glucuronic-acid derivative comprising an electrochemical oxidation step - Google Patents

Abstract

The invention relates to a method for preparing a composition of glucuronic acid or a glucuronic acid derivative, characterised in that it comprises a step during which a C1-protected glucose composition is submitted to an electro-oxidation treatment carried out: a) in the presence of an amino oxide; b) in a partitioned reactor; and c) at a temperature lower than 20° C, preferably lower than 16° C, and more preferably between 1 and 14° C.

Description

 PROCESS FOR PREPARING AN ACID COMPOSITION

GLUCURONIC OR GLUCURONIC ACID DERIVATIVE

COMPRISING AN ELECTROCHEMICAL OXIDATION STEP.

The subject of the present invention is a new process for preparing a glucuronic acid or glucuronic acid derivative composition, said process comprising an electrochemical oxidation step carried out under particular conditions, By "glucuronic acid composition" is meant any composition, whatever its form of presentation (liquid, solid, pasty ...) and its concentration, the dry matter (DM) is constituted mainly, ie for at least 50% by weight and up to 100% by weight (in dry / dry therefore), of glucuronic acid. Any other constituent of such a composition may especially consist of a glucuronic acid derivative and especially glucuronolactone. It may be, for example, a liquid composition containing mainly from 70 to 90%, in particular of the order of about 75-85%, of glucuronic acid (dry / dry), and from 5 to 30% , in particular of the order of about 15 to 25%, of glucuronolactone (dry / dry). By "composition of glucuronic acid derivative" is meant any composition, whatever its form of presentation and its concentration, the dry matter of which

(MS) is constituted mainly, i.e for at least

5O ¹ J by weight and up to 100? by weight (dry / dry), one or more derivatives of glucuronic acid.

These derivatives may especially be chosen from the grcαpe comprising; the salts of glucuric acid, glucuronolactone and the methylated, ethylated derivatives, isopropylated, benzylated, acetylated or phosphated glucuronic acid and its salts.

It may also be di-, oligo- or polysaccharides containing at least one unit corresponding to glucuronic acid or to one of its derivatives.

All of these compositions may not contain glucuronic acid as such or contain proportions of less than 50% (dry / dry), including less than a few%, or even less than 1% or even 0.5 % (dry / dry).

It can be compositions whose MS consists mainly, or exclusively or almost exclusively, of sodium glucuronate, glucuronolactone, methyl-, ethyl- or isopropyl-glucuronic acid, methyl-, ethyl- or isopropyl - sodium glucuronate, respectively.

Such compositions may consist, for example, in liquid compositions containing mainly from 5 to 45%, in particular of the order of about 15 to 45%, of glucuronic acid (dry / dry), and from 51 to 90%, in particular about 55 to 85%, glucuronolactone (dry / dry).

It can also be, as

"Glucuronolactone compositions" means compositions, solid or pasty, the MS of which consists exclusively or almost exclusively of glucuronolactone crystals.

Glucuronic acid and its lactonized form, in this case glucuronolactone ("GRL"), are products that find applications mainly in the food, pharmaceutical and cosmetic fields and in particular: in drinks, especially energizing, in pharmaceutical specialties, in particular with detoxifying or anti-fatigue effect. Among the processes for obtaining glucuronic acid or LRG, glucose is often used as raw material, which must, before any oxidation, be previously "protected in Cl", ie be converted into a derivative whose The hemiacetal function carried by the carbon in position 1 (Cl) of glucose has been protected against oxidation, for example by amination, esterification, etherification, acetalization or grafting.

The composition of "C1-protected glucose" intended to be subjected to oxidation may in particular consist of a composition of alkylated glucose, in particular methylated, ethylated or isopropylated, benzylated, acetylated or phosphated, in Cl.

It may also be di-, oligo- or polysaccharides containing at least one C1-protected glucose unit. In view of the oxidation of such compositions or more generally of any saccharide composition, a compound may then be used. of the "amine oxide" type as a catalyst.

The use of 2,2,6,6-tetramethylpiperidinyloxy ("TEMPO") and / or its derivatives is in particular widely described for about fifteen years, for example in the following documents:

Selective Oxidation of Monosaccharide Derivatives to Uronic Acids, N. J. DAVIS et al., TETRAHEDRON LETTERS, 1993, Vol. 34, N O -,

I pp. 1181-1184,

"Cataiytic oxidation of sugars by 4- (acetylamino) -TEMPO", K. ITO et al., Proc. Electrochem. Soc., 1993, Vol. 93-11, pp. 260-267,

"Electroorganic Synthesis 66: Selective Anodic Oxidation of Carbohydrates Mediated by TEMPO", K. SCHNATBAUM et al., Synthesis, 1999,

No. 5, pp. 864-872,

"TEMPO-mediated oxidation of maltodextrins and D-glucose: effect of pH on the selectivity and sequestering ability of the resulting polycarboxylates", J. F. THABURET et al.,

Carbohydrate Research, 330 (2001), pp. 21-29, "Selective oxidation of carbohydrates on Nafion®-TEMPO-modified graphite felt electrodes", E. M. BELGSIR et al., 2001, Electrochemistry Communications 3, pp. 32-35, patent application EP 1 027 931 A1 published in 2000 in the name of CHUGAI SEIYAKU Company. As regards the use of amine oxide for the specific preparation of uronic and derivative acids, in particular glucuronic acid and derivatives, the observation can be made that very few documents truly envisage and exemplify such use, especially in electrochemical oxidation processes of the saccharide. The chemical oxidation processes, without the use of saccharide electrooxidation means, have the major disadvantage of the use of sodium hypochlorite, which is undesirable considering the current constraints in terms of the protection of humans. and its environment.

In view of the preparation of uronic acids, the above-mentioned patent EP 1 027 931 mainly envisages two improvements to these chemical oxidation processes:

1) the immobilization of the amine oxide on a synthetic resin in order to reduce the rate of use and the risk of loss of this catalyst, and

2) the generation of sodium hypochlorite by electrochemical oxidation of a salt solution (usually sodium chloride and sodium carbonate) containing the saccharide to be oxidized, the hypochlorite regenerating the amine oxide continuously. In practice and as is apparent from FIG. 1 of patent EP 1 027 931, the oxidation reaction of the saccharide in the presence of amine oxide immobilized on resin takes place in a chamber ("reaction cell") which is separated from the chamber ("electrolysis cell") where sodium hypochlorite is generated electrolytically.

This, to avoid deterioration of the carrier resin and, especially, to limit the decomposition, by over-oxidation, of the amine oxide that may result from its presence near the electrodes of this electrolytic cell.

According to this technology, the saccharide subjected to oxidation: • is therefore always brought into contact with a halogenated oxidizing agent, the latter being in particular generated by electrochemical oxidation ("electrolytically oxidized product of a halogen-containing compound"), and • n ' is never put in the simultaneous presence of an amine oxide and an electrolytic cell.

This technology, if it seems relatively efficient in terms of oxidized saccharide yields, in practice, however, and especially because of the need to: physically separate the synthetic resin supporting the amine oxide on the one hand and the electrodes on the other hand (cf. particular means and methods for effectively depositing and effectively maintaining the amine oxide on said synthetic resin; using an organic solvent for amine oxide recovery.

With a view to preparing uronic acids, it has been recommended, for example in the aforementioned articles of SCHNATBAIM and BELGSIR, to overcome any use of halogenated oxidizing agents such as sodium hypochlorite, the regeneration of the amine oxide, for example TEMPO, being electrochemically, more precisely anodically. SCHNATBAUM envisages the electrochemical preparation in the presence of TEMPO of methyl glucuronic acid (in this case methyl α-D-glucopyranuronic acid) from C1-methylglucose (in this case methyl). D-glucopyranoside) as a substrate and this, in small undiffed glass-type glass chambers, in buffered carbonate medium and at 20 ^° C.

It is clear that despite a very large amount of TEMPO implementation (TEMPO / substrate molar ratio of 1/5) and a significant amount of electricity consumed (5.5 faraday / substrate irtcie), not industrially feasible, the molar yield of the desired product does not exceed 96%. In order to prepare the same product, BELGSIR envisages, at ambient temperature and in the presence also of a carbonate buffer (pH 10), to use, within a small compartment compartmentalized electrolyte ("modified micro flow cell") TEMPO immobilized on a synthetic polymeric film ("Nafion®") itself arranged on the graphite anode.

Despite these adaptations, it appears that the molar yield of the desired product (methyl α-D-glucopyranosiduronic acid) remains only of the order of 95%.

Moreover, the authors point out a very consistent loss (40-50%) of the TEMPO during electrolysis, which is unacceptable loss at an industrial stage, and in conclusion question the stability of the electrodes.

In addition, both in the SCHNATBAUM article and in that of BELGSIR, the electrochemical oxidation is conducted according to a qualifying process technology "with imposed potential", ie imposing a potential, for example 0.53V for BELGSIR, between working electrode and a reference electrode, for example based on calomel.

This type of "potential-imposed" process has the generally recognized advantage of minimizing the spurious reactions and of achieving a very high selectivity in the desired oxidized product.

However, it has the disadvantage of requiring the implementation of expensive equipment, especially at the industrial level, based on a three-electrode potentiostatic assembly.

It follows from the above that there is a need for a means at once simple, efficient, inexpensive but also truly extrapolabie at the stage. process for preparing glucuronic acid or one of its derivatives electrochemically in the presence of amine oxide.

In particular, there is a need for a method incorporating an electrochemical oxidation step which, even on an industrial scale, makes it possible to obtain a high molar yield of the specifically desired oxidized product without the need to preferably by exempting, from the implementation:

• long reaction times and / or high energy consumption,

High amounts of amine oxide and / or means, expensive and not always effective, immobilization of the amine oxide on a synthetic resin and / or an electrode,

• specific and costly equipment (three-electrode potentiostatic assembly) inherent to any "potential-imposed" process. In particular, a means is advantageously applicable to the industrial production of a molar yield at least equal to 97%, preferably at least 99% and up to 99.5-100%, in the oxidized product specifically sought. and usable as an intermediate for the preparation of glucuronic acid and / or GRL, these percentages being expressed in moles relative to the number of moles of the non-oxidized saccharide substrate used.

It is furthermore sought a means allowing the lowest possible energy consumption compared with the theoretical minimum quantity considered by those skilled in the art to be 4 faradays / mole of glucose unit in the saccharide substrate to be oxidized. And the Applicant Company found, after much research and analysis, that such a means could consist in the implementation, during the electrochemical oxidation reaction of the saccharide substrate in the presence of amine oxide. both selected temperatures in a relatively low range (<20 ° C) and a particular type of reactor, namely compartmentalized.

More specifically, the subject of the present invention is a process for the preparation of a glucuronic acid composition or a glucuronic acid derivative, characterized in that it comprises a step in the course of which a composition of C1 protected glucose to an electrooxidation treatment carried out: a) in the presence of an amine oxide, b) in a compartmentalized reactor, and c) at a temperature below 20 ^° C., preferably below 16 ^° C. and more preferably still between 1 and 140 ^° C.

By "compartmentalized reactor" is meant any reaction chamber comprising at least one cell, said cell comprising at least one anode, at least one cathode and at least one means of separation between an anolyte flow and a catholyte flow.

The separation means may in particular consist of a porous diaphragm, for example based on sintered glass or ceramic, or an ion exchange membrane, in particular a cationic membrane. The Applicant Company has observed that such a means of separation, in particular disposed in the environment close to the anode, or even in contact with it, makes it possible to significantly improve the percolation of the anolyte flow (generally containing the amine oxide and the C1-protected glucose composition through the anode.

Compared to a non-compartmentalized reactor, a significant increase in the productivity of the desired product has been observed / in particular because of the possibility of significantly increasing, for example doubling or tripling, the current density applicable to the system.

In addition, the presence of at least one separation means makes it possible to avoid any possible passage of hydrogen, generated at the cathode, through the anode and, more generally, in the event of a malfunction of the system limiting the formation. oxidized saccharide (amine oxide in an insufficient quantity or degraded, for example) and thus promoting the production of oxygen at the anode, to avoid any potentially dangerous contact between hydrogen and oxygen.

Hydrogen, a flammable gas, can thus follow a particular and risk-free treatment cycle. The compartmented reactor used in accordance with the invention may have a multitude of variants, in particular in terms of cell number (s), unit size of any cell, number of electrodes and means (s) of separation per cell and or by reactor, of nature and dimensions of these electrodes and means (s) of separation and their arrangement within any cell or reactor.

It may be used, for example, modular devices, in particular of the "Modular Membrane CeIl" type, as proposed by the EiectroCell Company.

Beyond the importance of the type of reactor as outlined above, the Applicant Company also found that to obtain high returns In the oxidized product sought, it was particularly advantageous, in the context of electrochemical oxidation in a compartmented reactor, to carry out said oxidation under temperature conditions which are decidedly lower than those envisaged in the prior art, in particular in the patent. EP 1 027 931 or the articles of SCHNATBAUM and BELGSIR cited above.

In particular, it has been found that, in the presence of temperatures of less than 20 ^° C., preferably of less than 16 ° C. and in particular of between 1 ° and 140 ^° C., molar yields at least equal to 99%, for example sodium salt of rαethyl α-D-glucopyranuronic acid, due, among other things, to a very good stability of the amine oxide under these conditions.

Particularly advantageously, these temperatures are between 2 and 12.5 ^° C., in particular between 4 and 11 ° C., ie in temperature ranges making it possible to obtain excellent yields of the desired product and excellent stability of the product. amine oxide but without harming the economy of the system that could result from a crippling increase in the power consumed induced by an increase in the voltage implemented due to the decrease in the conductivity of the medium at temperatures too low.

According to a first variant of the invention, the step during which a C1-protected glucose composition is subjected to an electrochemical oxidation treatment is furthermore carried out at a pH which is decidedly higher than those envisaged in the prior art. , in particular in the articles of SCHNATBAUM and BELGSIR mentioned above, namely at a pH greater than 10, especially between 10.2 and 13.5.

This pH may advantageously be between 10.5 and 13.0, i.e in a sufficiently high range to obtain, in this case, optimum productivity.

(Good conductivity of the medium and good kinetics of oxidation of the saccharide substrate by the amine oxide) without, however, being too high to avoid any oxidation of water, generating gaseous oxygen and consuming electricity.

According to a second variant, whether or not associated with the preceding one, the step during which a C1-protected glucose composition is subjected to an electrochemical oxidation treatment is not carried out "with imposed potential" as described in the articles. of SCHNATBAUM and BELGSIR above, but, on the contrary, is carried out "at imposed intensity".

According to this expression, well known to those skilled in the art, any process is understood according to which it is the intensity (quantity of electricity consumed / unit of time), generally expressed in amperes, which is imposed by the operator and not the oxidation potential, usually expressed in volts / reference electrode.

The Applicant Company has found that such a variant has the advantages, in addition to the simplicity and a more bearable equipment cost, of allowing much more precise control and reproduction of the duration of the electrooxidation reaction, an undeniable asset at the industrial stage. , in particular for operations carried out in discontinuous or "batch" mode.

According to another variant, associated or not with any variant described above, any anode present in the compartmentalized electrochemical oxidation reactor consists of a volumic anode, ie a porous anode or spongy in which the anolyte solution can truly percolate.

This volumic anode may notably consist of a graphite felt, a carbon felt or a porous or spongy material of a metallic nature, for example based on nickel or a nickel / chromium alloy.

The Applicant Company observed with astonishment that in the context of the invention, a graphite felt could be significantly more efficient than the other aforementioned porous or spongy materials, including a carbon felt having characteristics (geometrical surface, thickness, specific surface) yet identical or very close.

Any volumic anode, in particular of the graphite felt type, contained in the compartmentalized reactor used in accordance with the invention may advantageously have: a) a geometrical surface or "Electrode area", which does not take into account its thickness or its porosity , greater than 0.01 m ² , preferably at least 0.05 m ² , b) a thickness greater than 2 mm, preferably at least 2.5 mm, and / or c) a higher specific surface area at 0.3 mVg, preferably at least 0.35 πr / g.

Said anode volume may for example have: a) a geometric surface area of between 0.1 and 2 m "^'and in particular between 0.1 and 1 m, b) a thickness comprised between 3 and 15 mm and in particular between 3 and 12 mm and c) a specific surface area of between 0.4 and 1 μm / g and in particular between 0.5 and 0.8 μm / g.

Advantageously, any voluminal anode, for example any graphite felt, is placed directly in contact with a separation means, for example a cationic membrane, at least in the immediate environment, ie within 2 mm of a means of separation.

Any cathode also present in the compartmented reactor used according to the invention may also be a voluminal electrode, including a graphite felt, or conversely an so-called surface electrode, ie neither porous nor spongy, for example under the shape of a stainless steel plate. According to another variant of the process according to the invention, associated or not with any variant previously described, the electrochemical oxidation treatment is carried out with a relatively high current density, ie greater than 150 A / m ² , expressed in Amperes. relative to the total geometric area, expressed in m ² , of the anode or anodes present in the reactor.

This current density may especially be between 180 and 1000 A / m ² , preferably between 200 and 800 A / m ² .

Particularly advantageously, this current density is between 200 and 600 A / m ² , especially between 350 and 450 A / m ² .

According to another variant, associated or not with any variant previously described, the electrooxidation treatment is carried out by using, in at least one compartmented reactor cell, an anolyte whose dry matter (DM), including that brought by the substrate to be oxidized saccharide, is between 1 and 50 ^ι I, preferably between 2 and 40 I and more preferably between 5 and ¹ 3O I., expressed as dry weight relative to the total weight of the anolyte introduced into said cell. This MS of the anolyte flow may advantageously be between 7 and 20%.

The process according to the invention may also be characterized in that the electrooxidation treatment is carried out by using, in at least one compartmented reactor cell, an anolyte which has already circulated within said cell and / or from another cell.

Said anolyte which has already circulated in this way consists of a glucuronic acid derivative composition such as a composition of salt (s), for example sodium, methyl, ethyl or isopropyl α-D-glucopyranuronic acid. It is thus qualified by the skilled person of "background salt" and ensures the system conductivity sufficient, thus limiting the voltage within said cell.

Thus, during operations carried out in batch or batch mode, the anolyte obtained at the end of a reaction may advantageously be used, in whole or in part, as "bottom salt" for the preparation of the anolyte to be used. implemented for the next batch reaction.

For an anolyte used as "bottom salt" for the following reaction, the proportion, by weight or volume, of said anolyte thus used may in particular be between 5 and 95%, preferably between 10 and 80%, and more preferably still between 10 and 60%.

Advantageously, the rate of recirculation of the anolyte flow within any cell of the compartmented reactor is relatively high, ie greater than 10 l / min / m%, expressed in liters per minute but relative to the total geometrical surface, expressed in m, of the anode or anodes present in said cell. The Applicant Company has found that, in the context of the invention, it was of particular interest, in particular at the industrial stage, to implement an anolyte recirculation flow rate of between 20 and 250 l / min / m ² , preferably between 25 and 200 l / min / πr and more preferably still between 30 and 150 1 / min / m ² . This flow rate may especially be between 30 and 120 l / min / m ² and for example between 40 and 100 l / min / m ² .

It should be emphasized that in the context of the process according to the invention, it is possible to use, at any time and especially at the beginning of the reaction, in at least one cell of the compartmented reactor, an anolyte comprising a "bottom salt" containing other salts than glucuronic acid derivatives and in particular chloride and / or sodium sulphate.

According to another variant, associated or not with any variant described above, the electrooxidation treatment is carried out by implementing, in at least one compartmented reactor cell, an amount of amine oxide, in particular TEMPO or a TEMPO derivative, at least equal to 0.3 g / l, expressed as the dry weight of amine oxide per liter of anolyte introduced into said cell.

This amount may, for example, be between 0.4 and 2 g / l and most preferably between 0.5 and 1.5 g / l. It is advantageously between 0.6 and 1.2 g / l.

According to another optional feature of the process according to the invention, said amount of amine oxide, in particular TEMPO or a TEMPO derivative, used is between 0.1 and 2 ^c :, expressed in dry weight. of amine oxide relative to the dry weight of saccharide substrate ("C1-protected glucose composition") introduced into said cell. This amount may in particular be between 0.2 and 1.5% (dry / dry) and especially between 0.3 and 1.2% (dry / dry).

Although it is in no way excluded that the amine oxide may be wholly or partly attached to any solid support (anode, film, synthetic resin and / or other support), the process according to the invention implements, preferably, an amine oxide not fixed on a solid support. The electrochemical oxidation step according to the invention, a number of variants of which have been previously described, constitutes a simple, efficient, inexpensive and truly extrapolatable method at the industrial, preparative stage, with high yields and purity levels. compositions of glucuronic acid derivatives such as salts of, for example, sodium, methyl, ethyl or isopropyl α-D-glucopyranuronic acid.

These compositions are especially useful as intermediates for the synthesis of glucuronic acid and / or glucuronolactone (LRG).

For this purpose, the method according to the invention may in particular comprise successively, after the step

("Step a)" during which a C1 protected glucose composition is subjected to an electrooxidation treatment:

- at least one step b) during which the composition resulting from said treatment of electrooxidation, for example a composition of methyl ^<χ sodium -D-glucoρyranuronate, is subjected, preferably after a concentration treatment, a treatment electrodialysis, preferably bipolar electrodialysis, and / or passing through cationic resin, in order to transform it into a corresponding acid composition, for example methyl χ-D-glucopyranuronic acid, at least one step c) during which the composition resulting from said electrodialysis treatment and / or passing on cationic resin is subjected to a hydrolysis treatment, preferably chemical hydrolysis, in order to transform it into a glucuronic acid composition, and

at least one step d) during which the resulting glucuronic acid composition is subjected to a purification treatment, said treatment preferably being chosen from the group consisting of fading, demineralization and crystallization treatments.

At the end of step d), the resulting composition may consist of a glucuronic acid composition as defined above or of a glucuronic acid derivative composition as defined above and very particularly a glucuronolactone composition (LRG). ), which may especially be in the form of crystals.

The present invention will be described in more detail with the aid of the examples which follow and which are in no way limiting.

EXAMPLE 1 (COMPLIES WITH THE INVENTION)

In the context of this example, a reactor with separate compartments of electrolysis is used marketed by the company ElectroCell AB, type "Electro Prod CeIl" 2 cells, connected to a pH and temperature control system and equipped with:

- 2 anodes consisting of a 6 mm thick graphite felt, a specific surface area of 0.7 m ² / g and a total anodic geometrical surface area of 0.8 m ² , and 2 cathodes based on stainless steel. In this compartmented reactor, successively introduced into the anolyte tank: a) 30 1 of a bottom salt providing 4.7 kg, expressed by dry weight, of sodium methyl glucuronate, then b) 30 1 of water demineralized, 4 kg (20.6 moles) of methyl α-D-glucopyranoside and 24 g of "TEMPO". The MS of the anolyte flow is therefore about 14.5%.

In the catholyte tank, 80 l of demineralized water are introduced.

The electrolysis is carried out at constant intensity, namely 320 Amperes. The current density is therefore 400 A / m% expressed in Amperes relative to the total geometrical surface of the present anodes (0.8 m ² ).

The electrolysis is moreover carried out by maintaining the temperature of the reaction medium at a value of the order of 2 to 3.5 ^° C. and a pH of 12 with the aid of a 50% sodium hydroxide solution.

In addition, a recirculation flow of 50 1 / min is applied to the anolyte compartment, ie an anolyte flow recirculation flow rate of 62.5 i / min / m, expressed taking into account the total geometrical surface of the anodes present (0 , 8 m ² ).

The éiectrolyse is stopped after a 7hl5 reaction time when the power quantity actually consumed corresponds to 4,2 Faraday / mole of substrate, ie 105 ^'' of theory necessary for the oxidation of any primary alcohol function of the saccharide substrate in carboxylic function.

A solution of sodium methyl glucuronate is thus obtained with a molar yield of

99.4% compared to the methyl oc-D-glucopyranoside used.

Further tests carried out on the same plant and under the same conditions, including temperature (2 - 3.5 ^° C.), have shown that yields of sodium methyl glucuronate in the order of 99.4 -

99.5% could be obtained consistently over time.

EXAMPLE 1 shows that, by using a compartmentalized reactor, which is also already of consistent size, and a relatively low reaction temperature, it is possible to obtain and maintain a high molar yield over time, ie at least equal to 97% and can significantly exceed 99%, in the oxidized product specifically sought and this, excluding, in particular, the implementation:

• high energy consumption,

• long reaction times,

High amounts of amine oxide; specific and expensive means such as, for example, linked to the immobilization of the amine oxide on any support or to the three-electrode potentiostatic assembly necessary for any process; imposed potential ". In the context of additional tests conducted under the same general conditions as those described above, the Applicant Company has found that: overall, yields of the desired oxidized product of at least 98% were obtained in the most advantageous manner for reaction temperatures in the range of 1 to 14 ^° C., and

in particular, yields of the desired oxidized product equal to or greater than 99.5% could even be attained and maintained over time, provided that the reaction temperature was selected between 2 and 12.5 ° C., especially in the preferential range of 4 to H ⁰ C.

EXAMPLE 2 (COMPLIES WITH THE INVENTION)

In the context of this example, a reactor with separate electrolysis compartments marketed by the company ElectroCell AB, of the "Electro MP-CeIl" type with a single compartmentalized cell, connected to a pH and temperature control system, is used. equipped:

an anode consisting of a graphite felt having a thickness of 6 mm, a specific surface area of 0.7 mVg and a total anodic geometric area of 0.01 m ² , and

- 1 cathode made of stainless steel.

In this monocellular compartmented reactor, 0.5 l of demineralised water, 50 g (0.26 moles) of α-D-glucopyranoside and 0.3 g of "TEMPO" are introduced into the anolyte tank. the catholyte tank, introduced 1 1 of demineralized water. The MS of the anolyte flow is therefore about 9.1 - " The electrolysis is carried out at constant intensity, namely 4 Amperes. The current density is therefore 400 A / m ² , expressed in Amperes relative to the geometric surface of the single anode present (0.01 m ² ). The electrolysis is moreover carried out by maintaining the temperature of the reaction medium at a value of the order of 2 to 3.5 ^° C. and a pH of 12 with the aid of a 50% sodium hydroxide solution.

In addition, a recirculation flow of 1 1 / min is applied to the anolyte compartment, ie an anilic flow recirculation flow rate of 100 l / min / m ² , expressed taking into account the geometrical surface of the single anode present (0 , 01 m ² ).

The electrolysis is stopped after a reaction time of 7 h 15 at the moment when the quantity of electricity actually consumed corresponds to 4.2 faradays / mole of substrate, ie to 105% of the theoretical quantity necessary for the oxidation of any alcohol function. primary of the saccharide substrate in carboxylic function.

A solution of sodium methyl glucuronate is thus obtained with a molar yield of about 98% with respect to the methyl α-D-glucopyranoside used. Other tests conducted subsequently on the same plant and under the same conditions, including temperature (2 - 3.5 ⁰ C), have shown that yields of sodium methyl glucuronate of the order of 98 - 98.5 % could be obtained consistently over time.

Even if, in the present case, the yields obtained with the single-cell "Electro MP-CeIl" device are slightly lower than those observed with the "Electro Prod CeIl" device with 2 cells of EXAMPLE 1, the fact remains that all the objectives are achieved here, including yields of the specifically desired oxidized product which are higher than those described in the SCHNATBAUM and BELGSIR articles cited above.

EXAMPLE 3 (NOT COMPLYING WITH THE INVENTION)

In the context of this example, not in accordance with the invention, an experiment is carried out under conditions identical to those described for EXAMPLE 1 except that, in the present case, the reaction temperature has always been maintained at a temperature of at least 20 ^° C.

Under these conditions, a very significant drop in the molar yield of formation of sodium methyl glucuronate is observed, this yield being only about 60% approximately with respect to the methyl α-D-glucopyranoside used.

It follows that in the context of the invention, it is the specific association of a compartmentalized reactor and a temperature below 20 ⁰ C that achieves the technical and economic objectives set, recalled above.

EXAMPLE 4 (NOT CONFORMING TO THE INVENTION)

In the context of this example, not in accordance with the invention, an experiment is carried out under conditions identical to those described for EXAMPLE 1 except that, in the present case, a marketed electrolysis reactor is used. by ElectrcCell AB, of the "Electro MP-CeIl" type with only one cell, but this time, according to a non-compartmentalized variant. The reactor, connected to a pH and temperature control system, is therefore equipped with: 1 single anode made of 6 mm thick graphite felt, with a specific surface area of 0.7 μV and a total anodic geometric area of 0.01 m ² , and

- 1 single cathode based on stainless steel,

but no means of separation between anode and cathode. Under these conditions, a very significant drop in the molar yield of formation of sodium methyl glucuronate is also observed, this yield also being only around 60% approximately with respect to the methyl α-D-glucopyranoside used. . This confirms that, in the context of the invention, it is the specific association of a compartmentalized reactor and a temperature below 20 ⁰ C that achieves the technical and economic objectives set, recalled above.

Claims

A process for the preparation of a glucuronic acid composition or a glucuronic acid derivative, characterized in that it comprises a step in which a C1-protected glucose composition is subjected to a treatment of electrooxidation performed: a) in the presence of an amine oxide, b) in a compartmentalized reactor, and c) at a temperature below 20 ^° C., preferably below 16 ^° C. and more preferably still between 1 and 14 ^° C. ⁰ C.

2. Method according to claim 1, characterized in that the electrooxidation treatment is carried out at a temperature between 2 and 12.5 ^° C, in particular between 4 and 11 ° C.

3. Method according to one of claims 1 or 2, characterized in that the electrooxidation treatment is carried out at a pH greater than 10, in particular between 10.2 and 13.5.

4. Method according to claim 3, characterized in that the pH is between 10.5 and 13.0.

5. Method according to any one of claims 1 to 4, characterized in that the electrooxidation treatment is carried out at an imposed intensity.

6. Method according to any one of claims 1 to 5, characterized in that the compartmentalized reactor comprises at least one volumic anode, said volumic anode preferably having: a) a geometric surface greater than 0.01 itr, preferably less than 0,05 m, (b) a thickness greater than 2 mm, preferably not less than 2,5 mm, and / or c) a specific surface area greater than 0.3 m ² / g, preferably at least 0.35 mVg.

7. Method according to any one of claims 1 to 6, characterized in that the electrooxidation treatment is carried out with a current density greater than 150 A / m ^* , expressed in Amperes relative to the total geometrical surface, expressed in m ² , anode or anodes present in the reactor.

8. Method according to claim 7, characterized in that the current density is between 180 and

1000 A / m ² , preferably between 200 and 800 A / m ² .

9. Process according to any one of claims 1 to 8, characterized in that the electrooxidation treatment is carried out by using, in at least one compartmented reactor cell, an anolyte whose dry matter (DM) is included between 1 and 50%, preferably between 2 and 40% and more preferably between 5 and 30%, expressed by dry weight relative to the total weight of the anolyte introduced into said cell.

10. Process according to any one of claims 1 to 9, characterized in that the electrooxidation treatment is carried out by using, in at least one compartmented reactor cell, an anolyte which has already circulated within said cell. and / or another cell, the rate of recirculation of the anolyte flow within said cell being greater than 10 1 / min / m ² , expressed in liters per minute and relative to the total geometrical surface, expressed in m ² , of the anode had anodes present in said cell.

11. The method of claim 10, characterized in that the recirculation flow rate of the anolyte is between 20 and 250 l / min / rrr, preferably between 25 and 200 l / min / πr and more preferably still between 30 and 150 l / min / m ¹ .

12. Method according to any one of claims 1 to 11, characterized in that the electrooxidation treatment is carried out by using, in at least one compartmented reactor cell, an amount of amine oxide, in particular of TEMPO or a TEMPO derivative, at least equal to 0.3 g / l, expressed as dry weight of amine oxide per liter of anolyte introduced into said cell.

13. Process according to claim 12, characterized in that the amount of amine oxide is between

0.4 and 2 g / l and most preferably between 0.5 and 1.5 g / l.

14. Method according to any one of claims 1 to 13, characterized in that the electrooxidation treatment is carried out by implementing, in at least one compartmented reactor cell, an amount of amine oxide, in particular of TEMPO or a TEMPO derivative, between 0.1 and 2%, expressed by dry weight of amine oxide relative to the dry weight of C1-protected glucose composition introduced into said cell.

15. Method according to any one of claims 1 to 14, characterized in that it comprises successively, after the step ("step a)" during which a C1-protected glucose composition is subjected to a treatment. Electrooxidation:

- at least one step b) during which the composition resulting from said treatment of electrooxidation is subjected, preferably after a concentration treatment, a treatment of électrcdiaiyse, preferably ^r bipolar electrodialysis and / or passing on cationic resin, in order to convert it into a corresponding acid composition, at least one step c) during which the composition resulting from said electrodialysis and / or cationic resin treatment treatment is subjected to a hydrolysis treatment, preferably of chemical hydrolysis, in order to transform it into a glucuronic acid composition, and

at least one step d) during which the resulting glucuronic acid composition is subjected to a purification treatment, said treatment preferably being chosen from the group consisting of fading, demineralization and crystallization treatments.