MXPA97007010A - Procedure for the manufacture of d-eritr - Google Patents

Abstract

The invention relates to a process for the manufacture of D-erythrose, characterized in that an aqueous solution of a gluconic acid salt is brought into contact with hydrogen peroxide in the presence of a salt of a metal selected from the group consisting of cobalt, nickel and ruthenium. It also relates to a process for the manufacture of erythritol by the hydrogenation of D-erythrose asynchronous

Description

PROCEDURE FOR THE MANUFACTURE OF D-ERITROSA The subject of the present invention is a process for the manufacture of D-erythrose. More precisely, the subject of the present invention is a process for the manufacture of D-erythrose from gluconic acid, catalyzed by the ions of a metal chosen from the group consisting of cobalt, nickel and ruthenium, and is developed in an aqueous phase. The manufacturing processes of D-erythrose are already known. Among them, we can mention first the one proposed by RUFF (Ber. 32, 3674 (1899); 33, 1799 (1900)) and that it consists of oxidizing calcium D-arabinonate in the presence of oxygenated water. Such a procedure has the disadvantage of using as a raw material the arabinonic acid which is not a commercially available product. Other methods of making D-erythrose have been followed, such as the oxidation of D-glucose in the presence of lead tetraacetate, known as the PERLIN method (Perlin AS, Methods Carbohydr, Chem., 1962, 1.64). or the acid hydrolysis of the 2,4-O-ethylidene-D-erythrose obtained by the oxidation with 4,6-0-ethylidene-D-glucose periodate (Schaffer.RTM., J. Am. Chem. Soc. 81 (1959 ) 2838, Barker R. and Mac Donald DL, JA Chem. Soc. 82 (1960) 2301).

The D-eritrosa, as such, does not present a great interest, but it would be above all an important strong synthesis intermediary if it could be produced in large quantity and at low cost. In fact, a simple complementary stage of hydrogenation of D-erythrose makes it possible to obtain easily erythritol which is a polyol which can be used in multiple food applications, and especially as a non-cariogenic and hypocaloric substitute for sucrose. From this fact, the subject of the present invention is also a process for the manufacture of erythritol from the D-erythrose obtained according to the method of the invention. Although distributed in nature and assimilated all the time by man through his diet, erythritol was long ignored by the food industry, in view of the difficulties encountered to obtain it profitably. In the pharmaceutical industry, erythritol allows access through oxidation to L-eritrulose, a molecule that has an interesting functionality that gives it the possibility of being used for the synthesis of biologically active compounds. The studies made on the manufacturing processes of erythritol are divided globally between two major routes: chemical synthesis and biosynthesis via fermentation. However none of the known techniques in chemical synthesis such as the reduction of meso-tartrate, the oxide-reduction of D-ethylidene-4,6-D-glucose and the hydrogenation of hydrolysates of starch dialdehyde (T. Dola and T. Sasaki , Bio-Industry, (1988), 5, (9), 32) can reach a true industrial dimension. Although clearly more numerous than the chemical synthesis, the works conducted on the fermentation techniques are mostly interested in the production of erythritol as a secondary constituent. These works are applied to the production of erythritol by the yeasts Debaryomyces (US-A 2,986,495), Pichia (US-A 2, 986, 495), Candida (US-A 3, 756, 917), Moniliella (Antonie van Leeuwenhoek, 37 (1971) 107-118), and Aureobasi di um (JP-A 61 / 31,091). The results provided to date by the studies on the fermentation of erythritol, however, show a number of drawbacks, such as the formation of foam during fermentation, the speed of fermentation, the importance of by-products and especially the low performance, which compromises more the possibilities of industrialization. There is thus a need to improve a process that performs the manufacture of D-erythrose (and then erythritol by hydrogenation of the D-erythrose thus obtained) that does not have the limitations and / or disadvantages of the prior art. It is working on this research topic that the Applicant has perfected a new process for the manufacture of D-eritrosa by chemical route from gluconic acid or its salts. The process according to the invention again takes the principle of the method set forth by RUFF almost a century ago. This method allows to pass, generally of an aldonic acid having n carbon atoms to an aldose having (n-l) carbon atoms thanks to the combined action of ferric ions and hydrogen peroxide. However, yields in aldose are very modest. Thus, the conversion of gluconic acid to D-arabinose is carried out according to this method. Some improvements were made, later, by R.C. Hockett C.S. Hudson (J. Amer. Chem. Soc. 56, 1632-1633, (1934) and Ibid., 72, 4546, (1950)) and by US-A 3,755,294. The 60 percent yields of arabinose starting from gluconic acid are described there. One progress achieved by V. Bilik (CZ-232647, (1983)) using cupric ions (Cu (II)) as catalysts. Yields of the order of 70 percent are reached after laborious purification.

Recently identical results were recently obtained with a mixture of ferric and ferrous ions as catalysts (CZ-279002, (1994)). Finally, under particular conditions, EP-A 0,716,067 relates the yields of 78 percent in certain aldoses. During a large investigation of the RUFF reaction, the Applicant discovered that the cobalt, nickel, as well as the ruthenium salts catalyzed the reaction of gluconic acid with hydrogen peroxide to give, surprisingly, D-erythrose and not, as you could wait, D-arabinose. There is then loss of two carbon atoms with respect to the starting aldonic acid. Thus according to the invention, the process for the manufacture of D-erythrose is characterized in that an aqueous solution of a gluconic acid salt is contacted with hydrogen peroxide in the presence of a salt of a metal chosen in the group constituted by cobalt, nickel and ruthenium. A first advantage of such a process compared to the prior art fermentation processes is obviously to avoid all restrictions and problems related to fermentation techniques such as those mentioned above. A second advantage of the method according to the invention resides in the fact that it is extremely easy to use since both the raw material and the reagents are easily accessible. A third advantage of the process according to the invention is that D-erythrose is obtained with a very good yield close to the stoichiometry. Another advantage of the method according to the invention is that it finds its place easily in the food industry, because it uses water as a solvent, an undeniable advantage both in terms of toxicity and in terms of safety. The process of the invention employs a gluconic acid salt. In the present invention, gluconic acid salt is understood as the gluconic acid in free form, in lactonized form or as a mixture of these two forms, in the form of salts or in the form of esters. Thus, for example calcium gluconate, sodium gluconate or glucono-d-lactone agree perfectly. Gluconic acid is obtained in a known manner by the oxidation of glucose. This oxidation step can be conducted either chemically or microbiologically. The preferred chemical route within the framework of the invention consists in oxidizing glucose with the aid of air or oxygen in an alkaline medium and with the aid of palladium catalysts. A particularly preferred method is that described in U.S. Patent Number: A 4,845,208, of which the Applicant is an assignee, which consists in using as an oxidation catalyst, palladium fixed on activated carbon and excited to bismuth. It is also possible to consider oxidizing glucose electrolytically or with the aid of hypobromite. It can also be oxidized glucose microbiologically with the help of Gluconobacter or Aspergillus. Preferably the process of the invention is employed, in water, with a content of dry matter of gluconic acid salt comprised between 1 and 60 percent, preferably between 5 and 50 percent, and more particularly between 10 and 30 percent. The lower dry matter restrictions are imposed for obvious reasons of economy of evaporation of water and reduction of the size of the reagents. The upper dry matter restrictions are essentially imposed by problems of solubility or viscosity of the reaction medium. In the present description, all percentages are expressed with respect to gluconic acid (example: 50 mole percent means 50 moles of X per 100 moles of gluconic acid, and 50 percent means 50 grams of X per 100 grams of gluconic acid at beginning) . In the process according to the invention, the catalyst is constituted by ions of a metal selected from the group consisting of cobalt, nickel and ruthenium which may be carried in the form of any cobalt, nickel or divalent or trivalent ruthenium salt. Advantageously, the cobalt salts: acetate, acetylacetonate, halides, nitrate, sulfate, cobalt are preferred, for example, they are perfectly suitable. An amount of catalyst (cobalt, nickel or ruthenium salt) comprised between 0.001 and 50 percent, preferably between 0.002 and 20 percent and more particularly between 0.005 and 5 percent with respect to the gluconic acid salt used gives good results in the process according to the invention, both as regards the yield and the purity of the D-erythrose obtained. To the mixture of gluconic acid salt, catalyst and water thus made, hydrogen peroxide is added slowly under stirring, preferably in the form of hydrogen peroxide of 30% strength, at a ratio of 1 to 500 mole percent, preferably 50 to 400 mole percent and more particularly 100 to 300 mole percent with respect to the gluconic acid salt used. It is possible to use hydrogen peroxide in the form of oxygenated water of a wealth greater than 30 percent, especially for example up to 70 percent. The addition of the hydrogen peroxide is carried out at a rate of introduction such that the temperature of the reaction medium does not rise, preferably, beyond 50 ° C and more particularly beyond 35 ° C. Thus, the rate of introduction of hydrogen peroxide is generally between 30 minutes and two hours. Preferably, the process of the invention is employed at a temperature comprised between 0 and 100 ° C and preferably between 10 and 50 ° C. The lower temperatures lead reaction times too long and the higher temperatures, besides that they would need the use of pressure resistant reactors, would lead to a degradation of the products of the reaction. Temperatures of 20 to 40 ° C are then preferred particularly in the process of the invention. Still preferably, the process of the invention is employed at a pH comprised between 2 and 12, preferably between 5 and 8 and more particularly comprised between 6 and 7.

The D-erythrose obtained according to the process of the invention, under its crude form, can easily be hydrogenated catalytically. The hydrogenation of such a sugar is carried out in accordance with the rules of the art leading, for example, to the production of sorbitol from glucose. Ruthenium-based catalysts as well as Raney nickel catalysts can be used for this step. It is preferred, however, to use Raney nickel catalysts which are less onerous. In practice, from 1 to 10 weight percent of catalyst is used in relation to the sugar dry matter subjected to hydrogenation. The hydrogenation is preferably carried out on syrups whose dry matter is between 15 and 50 percent, in practice about 30 to 45 percent, under a hydrogen pressure of between 20 and 200 bars It can be done continuously or discontinuously. When operating discontinuously, the hydrogen pressure used is generally between 30 and 60 bars and the temperature at which the hydrogenation takes place is between 100 and 150 ° C. Care is also taken to maintain the pH of the hydrogenation medium by the addition of soda or sodium carbonate, for example, but without exceeding a pH of 9.0. This way of doing allows to avoid the appearance of cracking or isomerization products. The reaction is stopped when the content of the reaction medium in reducing sugars becomes less than 1 percent, preferably still less than 0.5 percent and more particularly less than 0.1 percent. After cooling of the reaction medium, the catalyst is removed by filtration and the D-erythritol thus obtained is demineralized on the cationic and anionic resins. In this stage, the syrups contain at least 90 percent D-erythritol and it is easy to purify them by crystallization after concentration and cooling of the solutions. The invention will be better understood by means of the examples which follow and which are solely intended to better illustrate the invention without wishing to reduce it to the embodiments expressly described and to the calcium gluconate salt used. In the examples that follow, all results are expressed in molar percentage.

EXAMPLE 1: Calcium monohydrate gluconate (115.7 grams, 0.255 moles), cobalt hexahydrate chloride (0.58 grams, 2.4 mmol) and water (1000 milliliters) are introduced into a double-cover reactor. The mixture is brought to a temperature of 30 ° C and to a pH of 6.5 by the addition of 2N sodium hydroxide. Oxygenated water (130 milliliters, 1.28 moles) is introduced during 70 minutes maintaining the temperature between 30 and 35 ° C and the pH at 6.5 with the help of 2N soda. At the end of the addition, the solution is stirred an additional hour. The pH is brought to between 2.5 and 3 by the addition of concentrated sulfuric acid (14 milliliters) in order to precipitate the calcium salts. After filtration, the pink solution has the following composition: D-erythrose (87 percent), D-arabinose (2 percent), gluconic acid (7 percent). The percentages given are those corresponding to the analytical results. The sum is not equal to 100 since there is sometimes a little arabinonic acid (2 percent) and other byproducts. These byproducts are: formic acid, "carbonates" and carbon dioxide. EXAMPLE 2: Calcium monohydrate gluconate (115.1 grams, 0. 25 mol), nickel hexahydrate chloride (2.24 grams, 9.5 mmol) and water (1000 milliliters) are introduced into a double-shell reactor. The mixture is brought to a temperature of 40 ° C and to a pH of 6.5 by the addition of 2N sodium hydroxide. Hydrogen peroxide is introduced at 35 percent (95 milliliters, 1.1 moles) for 70 minutes maintaining the temperature between 40 and 45 ° C and the pH at 6.5 with the help of 2N soda. At the end of the addition, the solution is stirred for three additional hours. The pH is brought to 2.5 by the addition of concentrated sulfuric acid (14 milliliters) in order to precipitate the calcium salts. After the filtration, the green solution has the following composition: D-erythrose (40 percent), gluconic acid (45 percent). The percentages given are those corresponding to the analytical results. The sum is not equal to 100 since there is also formation of glyceraldehyde (6 percent) and arabinose (2 percent). The byproducts of the reaction are: formic acid, carbon dioxide.

Claims (9)

1. Process for the manufacture of D-erythrose, characterized in that an aqueous solution of a gluconic acid salt is contacted with hydrogen peroxide in the presence of a salt of a metal selected from the group consisting of cobalt, nickel and ruthenium .

2. Process for the manufacture of D-erythrose according to claim 1, characterized in that the aqueous solution has a dry matter of gluconic acid salt comprised between 1 and 60 percent. Process for the manufacture of D-erythrose according to any of claims 1 or 2, characterized in that the salt of a metal chosen from the group consisting of cobalt, nickel and ruthenium is present in an amount comprised between 0.001 and 50 percent expressed in relation to the gluconic acid salt. Process for the manufacture of D-erythrose according to any of claims 1 to 3, characterized in that the hydrogen peroxide is used, preferably in the form of hydrogen peroxide of a richness of 30 percent, in an amount between 1 and 500 molar percent expressed with respect to the gluconic acid salt. 5. Process for the manufacture of D-erythrose according to any of claims 1 to 4, characterized in that it is operated at a temperature comprised between 0 and 100 ° C and preferably between 10 and 50 ° C. 6. Process for the manufacture of D-erythrose according to any of claims 1 to 5, characterized in that the working is carried out at a pH comprised between 2 and 12, and preferably between 5 and 8. 7. Method of manufacturing D -eritrous according to any of claims 1 to 6, characterized in that the salt of gluconic acid is obtained by oxidation of glucose effected with the aid of air or oxygen, in an alkaline medium, in the presence of palladium catalysts. 8. Process for manufacturing D-erythrose according to any of claims 1 to 6, characterized in that the salt of gluconic acid is obtained by oxidation of glucose by microbiological route. 9. Process for the manufacture of erythritol by the hydrogenation of D-erythrose, characterized in that the D-erythrose is obtained by the process according to any of claims 1 to 8.