FR2688780A1 - Process for the selective oxidation of a saccharide - Google Patents

Abstract

This process consists in reacting the said saccharide in aqueous solution with hydrogen peroxide and hydrobromic acid or bromine.

Description

PROCESS FOR SELECTIVE OXIDATION OF A SACCHARIDE
The present invention relates to a process for the selective oxidation of a saccharide comprising an aldehyde or hemiacetal reducing terminal group, in which said terminal group is selectively oxidized respectively to a carboxylic group (-CO2H-) or to a lactone group (-C02-) .

 The state of the art already includes such methods of selective oxidation of the hemiacetal end group of a saccharide, in which the hydroxyl groups are not oxidized.

Thus patent EP 0233816 (Roquette Frères) discloses a process for the oxidation of aldoses and in particular of
D-glucose to corresponding aldonic acids, process in which the oxidation is carried out in an alkaline medium, by means of a gas containing oxygen, using a catalyst consisting of at least one of the metals of the groups
IV, V and VI and palladium deposited on an inert support Preferably said metals are bismuth, lead, antimony, tin or selenium.

 Patent application EP 0232202 (Roquette Frères) discloses a process for the selective oxidation of di-, tri-, oligo- and polysaccharides comprising a terminal reducing function, as found in aldoses, to polyhydroxycarboxylic acids, process in which the oxidation is carried out in an alkaline medium, by means of an oxygen-containing gas, in the presence of a catalyst based on a noble metal chosen from the group consisting of palladium, platinum, rhodium and osmium, fixed on an inert support, said catalyst being doped using one or more metals from groups IV, V or VI of the periodic table.

 As recalled by the two documents above, aldonic acids and polyhydroxycarboxylic acids can advantageously be used as metal chelating agents, as agents intended for washing glass and metal articles or as additives for detergents, medicaments or even as food additives. Thus sodium gluconate is used for pickling metallic surfaces, as a setting retarder in hydraulic binders and as an admixture for concrete.

 The two above methods have the drawbacks inherent in the means used to carry them out. First of all they each require catalysts based on noble metals, therefore costly in investment. Doping is carried out with heavy metals which can interfere with the industrial use of the products obtained, in particular in their use in the food or pharmaceutical fields.

 The heterogeneity of the reaction medium requires filtration of the catalyst before any recovery of the final product. Oxygen-containing gas is blown into the alkaline medium, which can cause annoying foam. The alkaline medium can cause isomerization of certain unstable saccharides at high pH.

HSIsbell et al., J.Rés.Natl.Bur., L932,8,327 and 615; ibid., 1933,10,337; ibid., 1937,18,141; have shown that the
D-glucose and other aldohexoses and aldopentoses, are directly oxidized by bromine, in aqueous solution, to give delta-lactones isomerizing into thermodynamically more stable gamma-lactones.

2HBr + -C(O)-OR.However, this bromine oxidation has the drawback of theoretically requiring one mole of Br2 per mole of hemiacetal function to be oxidized to lactone according to the reaction -CH (OH) OR + Br2

2HBr + -C (O) -OR.

 In addition, the formation of 2 moles of HBr per mole of lactonic compound has the effect of rapidly increasing the acidity of the reaction medium.

 D. Miljkovic et al., ZB Matice Srp. Took.

Nanke, 1989, 77, 89-93, describe the oxidation of D-glucose by a mixture of hydrogen peroxide and iodine as a catalyst, in the presence of calcium carbonate. The best yield of calcium D-gluconate (18.8%) is obtained for an H2O2 / D-glucose molar ratio of 5/1.

The increase in the molar ratio causes a decrease in the yield of calcium D-gluconate probably resulting from an overoxidation of Dgluconic acid.

 By comparison, the best yield obtained by iodine oxidation in the absence of H2O2 was 59.5% for D-glucose / I2 / CaCO3 molar ratios equal to 1/1/2.

These authors noted that D-fructose was not oxidized under the conditions of optimal oxidation of D-glucose by the mixture H2 02 + 12
These authors conclude by estimating that the optimal yield of calcium D-gluconate is obtained for an oxidation of D-glucose by a stoichiometric amount of elemental iodine at 900C for 3 hours, in neutral medium.

Thus the comparison of the yields above, ie 59.5% for oxidation by iodine only and 18.8% for the use of the couple I2 / H202, clearly indicates that iodine alone is clearly more efficient than The mixture
H202 and iodine.

 The object of the present invention is to define a process for the selective oxidation of the reducing terminal function of a saccharide, which would not have the drawbacks mentioned above, while leading to a satisfactory yield to allow industrial development.

 This object is achieved according to the present invention by a method of selective oxidation of a saccharide comprising an aldehyde or hemiacetalic reducing terminal group, in which said terminal group is selectively oxidized respectively to a carboxylic group (-CO2H) or to a lactonic group. (-COO-), characterized in that said saccharide is reacted in aqueous solution with hydrogen peroxide and a halogenated compound chosen from hydrobromic acid and bromine.

 Unexpectedly, choosing bromine or hydrobromic acid instead of iodine, in the presence of H2O2, as will be shown in more detail in the examples which follow, makes it possible to obtain much better yields, even not optimized. This is how calcium D-gluconate is obtained with a non-optimized yield of recrystallized product of 92% relative to the Dglucose reacted.

 Preferably, the process according to the invention is carried out while maintaining the reaction medium at a pH of between 0.5 and 7. Even more preferably the pH is maintained between 0.5 and 4.

 Advantageously, the temperature of the reaction medium is maintained between 20 and 600C.

 Preferably, the hydrogen peroxide / bromine molar ratio is between 1 and 200.

 Also preferably, the hydrogen peroxide / HBr molar ratio is between 0.5 and 100.

 Advantageously, the molar ratio of hydrogen peroxide / said end group is between 5 and 1.

 The term saccharide includes mono-, di-, water-soluble polysaccharides at weight concentrations between 50 and 200 g per 100 g of water. The saccharide is chosen in a preferred manner from aldopentoses, aldohexoses, disaccharides or else a starch hydrolyzate having a degree of polymerization (DP) from 1 (for example glucose) to a DP of 20, such as for example glucose syrups used in patent EP 0232202.

 The present invention will be better understood using the following examples given purely by way of illustration.

 Hydrogen peroxide and hydrobromic acid are introduced in the form of an aqueous solution, the title of which (for example 30%) expresses the mass in grams of H 2 O 2, or of HBr per 100 grams of solution.

EXAMPLE 1
Oxidation of D-glucose to D-qluconic acid
In a closed chamber (500 ml screw bottle), D-glucose (10 g, 55 mmol) is dissolved in an aqueous solution of hydrogen peroxide (30%, 5 ml, 49 mmol) with magnetic stirring and ambient temperature of 200C. Hydrobromic acid (40% aqueous solution, 2 ml, 13.6 mmol) is added all at once, while continuing the stirring. After 24 hours, an aqueous solution of hydrogen peroxide is added (70%, 2.5 ml, 68 mmol) and the reaction is continued for another 24 hours.

Then the solution obtained is added with water (25 ml) and freed from the residual bromine by air bubbling, before being added with calcium hydroxide (2 g), heated and concentrated under reduced pressure to a volume d '' about 20 ml. Calcium gluconate, which spontaneously crystallizes from the solution after a few hours, is isolated by filtration and recrystallized from water. 11 g (92%) of a product having the following characteristics are obtained
(alpha20 = + 8.50 (c = 3, water)
13C NMR (D20, pH = 7, Me2CO, delta 31.04)
178.7 (Cl); 74.4, 72.6, 71.3, 70, 9 (C-2 to
C-5); 62.7 (C-6).

By way of comparison, the literature gives the following values for D-gluconic acid [alpha] D = + 8.50 (H2O) Hudson and Isbell
J. Am. Chem. Soc, 1929.51,
2225.

13 C NMR (pH 14): delta 179.8 (Cl); 75.2; 73.8;
72.4; 72.0 (C-2 to C-5); 63.6 (C
6).

Isbell, Carbohydr. Res., 1981.90,
123
EXAMPLE 2
Oxidation of D-xvlose to D-xvloniaue acid isolated in the form of ammonium xvlonate
In a closed chamber (500 ml screw bottle), D-xylose (8 g, 53.3 mmol) is dissolved in an aqueous solution of hydrogen peroxide (30%, 5 ml, 49 mmol) with magnetic stirring at room temperature.

 Hydrobromic acid (40% aqueous solution, 1 ml, 6.8 mmol) is added all at once at room temperature of 200C, while continuing the stirring. After 24 hours an aqueous solution of hydrogen peroxide (30% 5 ml, 49 mmol) is added and the reaction is continued for another 24 hours.

 H2O2 / water (30%, 5 ml) and HBr (40%, 0.5 ml, 3.4 mmol) are then added and left for 72 hours.

13
A C NMR spectrum (D20, pH 2, Me2CO, delta 31.04) is then produced on an aliquot of the reaction mixture. The spectrum makes it possible to determine that at least 85% of the starting D-xylose has been transformed into Dxylonic acid (comparison of the intensities of the peaks of D-xylose: delta 97.5 and 93.1 (Cl); 66.1 and 61.9 (C-6) with peaks 177.9 and 176.5 (Cl); 63.3 and 59.9 (C-6) of the corresponding aldonic acid forms.

 The residual bromine is then removed by bubbling air, then the solution is added with ammonia (20%) to pH 9. The ammonium salt, which crystallizes from the solution, is isolated by filtration (6.9 g, 70.3%). A second crystallization, after concentration of the mother liquors, makes it possible to recover further ammonium xylonate (1 g, 10.2%), which leads to an overall yield of 80.5%.

This salt has the following characteristics [alpha] D = + 1800 (c = 3, H20)
PF = 121 C.

By way of comparison, the literature (Zinner,
Voigt and Voigt, Carbohydr. Res., 1968,7, p. 48) gives the following values
Ealpha] 20 = + 19.10 (c = 2, H2O); PF = 118 1220C
EXAMPLE 3
Maltose oxidation to maltobionicrue acid
Hydrobromic acid (aqueous solution) is added to a closed enclosure (100 ml) containing maltose (5 g, 13.9 mmol) dissolved in an aqueous solution of hydrogen peroxide (70%, 5 ml, 136 mmol) at 40%, 0.5 ml, 0.34 mmol). The solution, protected from light, is left under stirring for 48 hours, then an aliquot is taken 13 which is analyzed in 1 C NMR.

 The oxidation rate, estimated on non-anomeric C-i carbons, carbons which resonate at 100.6 and 100.2 p.p.m. for the oxidized form and at 99.8 p.p.m. for the starting maltose, is 61%.

 The volume of the reaction solution is then reduced by approximately half under reduced pressure. The solution thus obtained is added up with a solution of hydrogen peroxide (70%, 5 ml, 136 mmol) and hydrobromic acid (40% aqueous solution, 0.5 ml, 0.34 mmol). The reaction is continued, protected from light, with magnetic stirring for 48 hours. An analysis by R.M.N. C on an aliquot under the conditions described above, shows an overall oxidation rate of approximately 90% to maltobionic acid.

EXEHPLE 4
Oxidation of maltose to maltobionic acid isolated in the form of its brucine salt
The usual precautions are taken to take into account the toxicity of brucine.

 In a closed enclosure (100 ml) containing maltose (5g, 13.9 mmol) dissolved in an aqueous solution of hydrogen peroxide (70%, 2.5 ml, 68 mmol) is added hydrobromic acid (solution 40% aqueous, 0.25 ml, 0.17 mmol). The solution, protected from light, is left to stir. After 24 hours, an aqueous solution of H 2 O 2 (70%, 2.5 ml, 68 mmol) and hydrobromic acid (40% aqueous solution, 0.25 ml, 0.17 mmol) are added.

 After 48 hours, a spectrum of R.M.N. C, carried out on an aliquot of the reaction mixture, makes it possible to determine that at least 85% of the starting maltose has been transformed into maltobionic acid (comparison of the intensities of the peaks 99.8 (Cl) for the maltose and 100.2 and 100 , 6 (Cl) for the oxidation product). The residual bromine is removed by bubbling with air, then the solution is added with water (20 ml) and brucine (6g, 13.9 mmol).

The brucine salt crystals are filtered (8.2 g, 75%),
PF = 151 C,
[alpha] D = + 33O (c = 1.3; H2O)
By way of comparison, the literature (Carbohydrate, PM Collins ed., Chapman 1987) gives the following characteristics for brucine maltobionate
PF = 1530C
[alpha] D = + 38.1 (H2O)
EXAMPLE 5
Oxidation of maltodextrins to olvhvdroxy-carboxylic acids.

 The maltodextrins used have an average degree of polymerization (DPm) of 5 and come from the hydrolysis of a starch. They are marketed under the name Glucidex 19 by the company Roquette Frères (France).

 In a closed enclosure (100 ml) containing an aqueous solution of hydrogen peroxide (70%, 2.5 mi, 68 mmol) are added maltodextrins (5 g, 31 mmol of anhydroglucose corresponding to 5.8 m equivalent of dextrose) and hydrobromic acid (40% aqueous solution, 0.25 ml, 0.17 mmol). The highly viscous solution is stirred magnetically away from light for 96 hours at 200C. An aliquot is then taken and analyzed 13 in R.M.N. C compared to the starting product. We note on the spectrum of the oxidized product the disappearance of signals 96 (C-1 B) and 92 (C-1 alpha) corresponding to the hemiacetal reducing ends of oligosaccharides and the appearance of signals 176 (C -1), 82 (C-3) and 62.5 (C-6) corresponding to the oxidation of these ends to aldonolactone. The reaction solution is then added with water (5 ml) and the oligosaccharides are precipitated by addition of ethanol (100 ml) and filtered. The solid product collected is taken up in water (50 ml) and lyophilized (3, 5 g, 70%). A potentiometric titration, carried out by adding a sodium hydroxide solution (0.0468 N), taking into account the inflection point of the neutralization curve, makes it possible to determine an overall acidity rate of 18, 6% taking into account all of the bromine introduced at the start. The equivalent dextrose level of the starting compound is 18.8%, indicating a practically quantitative conversion of the starting maltodextrins into polyhydroxy-carboxylic acids.

EXAMPLE 6
Oxvdation of maltodextrins to Polvhvdroxv-carboxvliaues acids
The maltodextrins used are the same as in Example 5.

In a closed enclosure (100 ml) containing a solution of hydrogen peroxide (70%, 2.5 ml, 68 mmol) are added maltodextrins (5 g, 31 mmol of anhydroglucose corresponding to 5.8 m. Equivalent of. dextrose) and hydrobromic acid (40% aqueous solution, 0.25 ml, 0.17 mmol). The highly viscous solution is stirred magnetically away from light for 96 hours at 200C. An aliquot is then taken and analyzed
13 in C NMR compared to the starting product. The evolution of the oxidation reaction is noted as in Example 5 above.

 In order to remove the residual bromine, the reaction solution is then added with water (25 ml) and neutralized with sodium hydroxide (0.0468 N, 172 ml). The lyophilized product (5.6 g) is washed with methanol, filtered, redissolved in water (50 ml) and lyophilized again (5.2 g, 100%). A microanalysis indicates that 0.08% of residual bromine remains.

Claims (11)

 RETURN! > ICTIONS  1. Method for the selective oxidation of a saccharide comprising an aldehyde or hemiacetal reducing terminal group, in which said terminal group is selectively oxidized respectively to a carboxylic group (-CO2H) or to a lactonic group (-COO-), characterized in what is reacted in aqueous solution said saccharide with hydrogen peroxide and a halogenated compound selected from hydrobromic acid and bromine.  2. Method according to claim 1, characterized in that said aqueous solution containing said saccharide, H2O2 and the halogenated compound is maintained, at a pH of between 0.5 and 7.  3. Method according to claim 2, characterized in that said pH is maintained between 0.5 and 4.  4. Method according to one of claims 1 to 3, characterized in that the temperature of the aqueous solution is maintained between 20 and 600C.  5. Method according to one of claims 1 to 4, characterized in that the hydrogen peroxide / bromine molar ratio is between 1 and 200.  6. Method according to one of claims i to 4, characterized in that the hydrogen peroxide / HBr molar ratio is between 0.5 and 100.  7. Method according to one of claims 1 to 6, characterized in that the molar ratio of hydrogen peroxide / said end group is between 5 and 1.  8. Method according to one of claims 1 to 7, characterized in that the saccharide is an aldopentose.  9. Method according to one of claims 1 to 7, characterized in that the saccharide is an aldohexose.  10. Method according to one of claims 1 to 7, characterized in that the saccharide is a disaccharide.  11. Method according to one of claims l to 7, characterized in that the saccharide is a starch hydrolyzate.