CS234623B1 - Process for producing D-tnannitol - Google Patents

Abstract

O-Mannitol is produced by the method according to the invention, the essence of which consists in catalytically hydrogenating dextran calcinations and, after the hydrogenation is completed, the catalyst is filtered off and the filtrate is concentrated, D-mannitol is allowed to crystallize.

Description

The invention relates to the production of the sugar alcohol D-matinitol from dextran stillage, i.e. mother liquors, after fermentative production of dextran from sucrose using Leuconostos mesenteroides, containing predominantly D-fructose, by catalytic hydrogenation at elevated temperature and elevated pressure.

D-Mannitol is in pure form, used in medicine and as a raw material in the chemical industry.

D-Mannitol is widespread in nature both in the lower and in the wild. higher plants. It was discovered in 1808 in manna, a sweet pathological effusion from manna ash (fraxinus ornus). Some seaweed, especially brown seaweeds, also have a high content of D-mannitol. It has also been found in lichens and higher fungi.

Of these plant raw materials, D-mannitol is most often obtained by alcohol extraction. Some of these natural sources of D-mannitol have recently been used to produce D-mannitol, such as manna from Fraxinus rotundifolius and F. ornus, or some brown seaweeds. Described the isolation of D-mannitol from the fermentation ^of methyl di.a after biosynthesis of dextran in which a small amount of by-product (Vaněček R. Čs.pat. 102742, 1962).

Today, D-mannitol is mostly produced by catalytic hydrogenation of readily available suitable hexoses in an aqueous or aqueous-alcoholic solution (Brit. Pat. 801732, 1958). The highest yield is provided by the reduction of D-mannose, which proceeds with almost 100% yield; the disadvantage, however, is the high cost of D-mannose, which is produced by the hydrolysis of mannan, polysaccharides present, for example, in the fruit of the tropical palm Phytelephas macrocarpa. Hydrogenation of D-fructose solutions gives D-mannitol in addition to D-sorbitol in 50% yield; however, pure D-fructose is relatively expensive as a raw material. Among the cheaper raw materials containing D-fructose, sucrose is also suitable, which after hydrolysis yields a 1: 1 mixture of D-glucose and D-fructose.

234 623

The yield of D-mannitol from sucrose is 25%, but practically less is obtained since the separation of D-mannitol from the mixture containing 25% D-mannitol and 75% D-sorbitol does not proceed quantitatively. A somewhat higher yield of D-mannitol is provided by hydrogenation of the so-called fructose syrup, a mother liquor from the production of crystalline D-glucose from sucrose, wherein the ratio of D-glucose and D-fructose is approximately 4-6 (Kulhánek M. a. Tadra M · Ss. U.S. 135989, 1970). D-Mannitol can also be prepared by catalytic hydrogenation or electroreduction of alkaline D-glucose solutions and isomerization of D-fructose so that D-mannitol can be obtained in yields of up to 20%. Biochemical methods for preparing D-mannitol by microbial conversion of D-fructose are also known. which is carried out by heterofermentative lactic bacteria with a relatively high yield. More recently, the biotransformation of D-glucose in D-mannitol by some fungi has also been described. Waste waters from dextran production have also been used as a source of D-fructose for the biochemical preparation of D-mannitol (Behrens H. et al., GDR Pat. 51818, 1966). Although these fermentation processes provide high yields of D-mannitol, they are economically disadvantageous because they are operated at relatively low concentrations of sugar solutions (optimum concentration is 7-8%) & processing of these solutions places considerable demands on cleaning operations.

SUMMARY OF THE INVENTION The dextran stillage containing D-fructose as the main constituent is subjected to catalytic hydrogenation in the presence of Raney nickel at a pH of 6 to 7, a temperature of 60 to 120 ° C gradually increased over 4 to 6 h and a pressure of 2 to 10 MPa. and the resulting solution containing D-mannitol is acidified to pH 3-5 or deionized after filtering off the catalyst, concentrated under reduced pressure and cooled; Crude D-mannitol crystallizes, which is purified by recrystallization from hot water. The yield of pure D-mannitol thus obtained, having a melting point of 166-167 ° C, is about 90%, calculated on the pure D-fructose present.

Dextran stillage represents waste from the fermentation production of dextran for pharmaceutical and / or pharmaceutical production. technical purposes. Are the mother liquors after isolation of the so-called native dextran from the fermentation broth after precipitation with alcohol (methanol, ethanol or isopropanol) from which the alcohol has been evaporated and which have been eventually? thickened for further use; depending on the degree of concentration, they may have up to 70% dry matter, of which about 50% fructose. The rest of the dry matter represent

234 623 small amounts of minor metabolites such as D-mannitol, leucrose, D-glucose oligosaccharides, low molecular weight dextran or D-glucose and sucrose from incomplete fermentation media, inorganic salts, mainly phosphates and small amounts of nitrogen organic substances from media components ·

Dextran stillage suitable for hydrogenation contains 10 to 50% fructose, the by-products present are not defective. If the acidity of the dextran stillage is less than pH 6, it is adjusted to a neutral reaction. Calcium carbonate is preferably used as neutralizing additive and pH regulator in an amount of about 1% to the content of reducing sugars present. Raney nickel is used as a catalyst, used for example in the production of D-sorbitol from D-glucose. The hydrogenation itself is carried out under a hydrogen pressure of 2 to 10 MPa and at a temperature which is maintained for 2 to 3 hours in the range of 60 to 80. ° C and after this time, when hydrogen absorption ceases, it increases to 100-120 ° C for 2.3 h. Maintaining these temperatures is advantageous in order to hydrogenate the present D-fructose at a temperature below 100 ° C and avoid darkening of the solution due to its partial destruction; only then can the temperature be raised to 100 to 120 ° C to complete the reduction of the remaining carbohydrates present (the optimum for D-glucose is 100 to 120 ° C). Hydrogenation is complete when the absorption of hydrogen stops and the solution no longer contains any reducing agents.

Dextran stillage solutions after hydrogenation contain D-mannitol as a major component. After separation of the catalyst by filtration, they are processed to crystalline D-mannitol in a conventional manner, e.g. by evaporating to a smaller volume and cooling or adding a lower aliphatic alcohol, e.g. methanol. The solutions prior to crystallization of D-mannitol can be deionized to remove any inorganic salts present, or to adjust the pH to 3-5 with dilute hydrochloric acid and keep the calcium salts present in solution.

The crystallized crude D-mannitol is separated from the mother liquors by filtration or by centrifugation and washing with water or a dilute lower aliphatic alcohol such as methanol. After drying, m.p. 150-165 ° C. It is purified by recrystallization in a known manner, i.e. by dissolving in hot water, decolourising the resulting solution with activated carbon and hot filtration. By cooling these solutions to room temperature (18 to 22 ° C) or preferably to 5 to 5 ° C, pure D-mannitol crystallizes which is separated by filtration from the mother liquors.

234 623 lyes, washed with cold water or dilute methanol and dried at 50-80 ° C. The pure product obtained had m.p. 166 to 167 ° θ ·

The following examples illustrate the invention but do not limit it in more detail. ,

Example 1

In a 3 L high pressure autoclave, 1 L dextran stillage (40% solids content, 29.8 g fructose content in 100 mL) is hydrogenated in the presence of 3 g calcium carbonate & 50 mL Raney nickel at 70-80 ° C and hydrogen pressure 6-8 MPa for 2 h and then the temperature is raised to 110-120 ° C and hydrogenation is continued for a further 2 hours. When the hydrogen uptake ceased, the contents of the autoclave were allowed to cool and filtered from the catalyst. A clear and almost colorless solution containing no reducing agents (Fehling's solution) was evaporated under reduced pressure at 50 ° C to a smaller volume (50-60% solids content). The solution was diluted with 200 mL of methanol and left at room temperature for 48 h. The crystallized crude D-mannitol is filtered, washed with 50% methanol and dried in a vacuum oven at 60 ° C. The yield of crude material is 140 g, mp 152-156 °. This crude product is dissolved in 400 ml of water at 80 ° C, the hot solution is clarified and decolorized by filtration with 2 g of activated carbon (carboraffin) and evaporated under reduced pressure starting crystallization. The major portion of pure D-mannitol crystallizes within 24 h at 3 ° C; Filter, wash with cold 50% methanol and dry in a vacuum oven at 80 ° C. Further portions of pure D-mannitol are obtained from the mother liquor by evaporation to a smaller volume. The total yield of chips was 128 g, i.e. 85% of theory (calculated on D-fructose present in dextran slices). Melting point 166-167 ° C.

Example 2,

In a 3 L high-pressure autoclave, 1.5 L of dextran stillage (30% dry matter, fructose content 22.9 g in 100 mL) is hydrogenated in the presence of 5 g of calcium carbonate and 50 mL of Raney nickel (W-2). of hydrogen at 70 to 78 ° C for 2 h at which time the temperature was raised to 110 to 115 ° C and continued hydrogenation for a further 2 h. After cooling, the contents of the autoclave were filtered from the catalyst. The solution does not contain

234,623 reducing agents and has a pH of 8.3. Acidify with dilute hydrochloric acid to pH 4 and evaporate to 60% solids content under reduced pressure at 50 ° C. After dilution with 300 ml of methanol, D-mannitol crystallizes at room temperature; isolation was carried out as in Example 1. The yield of crude dried product was 155 g, mp 153-156 ° C. It is dissolved in 450 ml of water at 75 ° C and clarified by filtration and 3 g of activated carbon. The colorless solution was evaporated to incipient crystallization and cooled to 5 ° C. After 48 h, the pure product is filtered off with suction and the mother liquors are evaporated to further fractions. The total yield of pure D-mannitol is; 150 g, i.e., 87% of theory to the initial D-fructose content. Melting point 166-167 ° C.

Example 3

In a 3 L autoclave, 1 L of dextran stillage (30% solids content, 22.9 g D-fructose content in 100 ml) is hydrogenated with stirring in the presence of 2 g calcium carbonate and 25 ml Raney nickel (W-2) under the same conditions as in Examples 1 and 2. After completion of the hydrogenation and separation of the catalyst, the solution is deionized on columns of cation exchange resin (Wofatit KPS-200; Reform, 200 mL volume) and anion exchange resin (Wofatit SBK; 0H ** form, 250 mL volume). impurities present, in particular inorganic salts. The deionized solution was evaporated under reduced pressure at 50 ° C to a dry matter content of 65%, diluted with 200 ml of methanol and cooled to 2-5 ° C. After 48 h, the crude D-mannitol crystallized (m.p. 158-164 ° C) was recrystallized in the same manner as in the previous examples. 106.5 g of pure D-mannitol are obtained, i.e. 92% of theory. Melting point 166-167 ° C ·

Claims (7)

SUBJECT OF THE INVENTION 234 623 A process for the preparation of D-mannitol, characterized in that D-mannitol ae is obtained from catalytic hydrogenation at a pressure of from 2 to 10 MPa at a temperature gradually increased from 60 to 120 ° C over a time period of 4 to 50% fructose. up to 6 hours while maintaining the pH at 6-7, then after completion of hydrogenation, removal of the catalyst and concentration of the filtrate, and D-mannitol is crystallized. 2. The process according to claim 1, wherein the catalytic hydrogenation is carried out under a hydrogen pressure of 5 to 8 MPa. 3. A process according to claim 1, wherein Raney nickel is used as the hydrogenation catalyst. 4. The process of claim 1 wherein the hydrogenation is carried out at 60 to 80 ° C for 2 to 3 hours and then at 100 to 120 ° C for a further 2 to 3 hours. 5. The method of claim 1, wherein calcium hydrogen carbonate is used to maintain the pH at about 6-7 during hydrogenation. 6. Process according to claim 1, characterized in that after the hydrogenation has been completed and the catalyst has been separated off, the solution is acidified to pH 3 to 5 with hydrochloric acid. 7. The process of claim 1, wherein after the hydrogenation and catalyst separation the solution is deionized. Printed by Moravian Printing Works,