SU1538900A3 - Method of producing d-glucosaccharoascorbic acid or its salts - Google Patents

Abstract

NEW MATERIAL:D-glucosaccharoascorbic acid or its salt. USE:Antioxidant. PREPARATION:2-Keto-D-glucaric acid or its 2,3-O-acetal or ketal or their salt or their mixture is treated with preferably 0.2-50 times mol of an acid (e.g. hydrogen chloride). The treatment is carried out usually using water as a solvent preferably at 10-100 deg.C for 20min-12hr.

Description

This invention relates to a process for the preparation of D-glucosaccharoascorbic acid or its salts, which can be used to improve the quality of food products.

The purpose of the invention is to obtain a novel compound D-glucosaccharoascorbic acid, which has improved antioxidant properties.

This goal is achieved in that according to the method, 2-keto-B-glucaric acid or its 2,3,0-acetal or ketal is treated in the form of a mineral acid, an organic acid or in the form of an ion exchange resin in the H + form.

Example 1. A mixture of 24.8 g (0.1 mol) of 2.3-0-isopropylidene-2-keto-P-glucarinic acid and 50 ml

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31538900

concentrated hydrochloric acid is stirred at 50 ° C for 20 minutes. The reaction mixture is concentrated to dryness under reduced pressure, 10 ml of distilled water is added to the residue, and the solution is passed through

a column filled with 50 ml of Shirasagi activated carbon, of special purity for chromatography, manufactured and marketed by Takeda Chemical, Co., Ltd., using water. After elution with water, the eluate is concentrated at

within 30 min. The reaction mixture is concentrated to dryness under reduced pressure, a small amount of activated carbon and 50 ml of distilled water are added to the residue, and the mixture is heated for about 5 minutes and then filtered while hot. The filtrate is evaporated to dryness under reduced pressure, a small amount of dichloromethane is added to the residue, the insoluble matter is collected by filtration, dried, and 1.69 g of D-glucosaccharoascorbic acid are obtained in

reduced pressure. Add 15 monohydrate to the residue. Purity 98.0%.

A small amount of dichloromethane is added and the insoluble matter is collected by filtration, dried, and 19.0 g of crude D-glucosaccharoascorbic acid monohydrate are obtained. Purity 98.5%. Yield 90.0%.

By recrystallization of the obtained product, D-glucosaccharoascorbic acid was obtained from dry acetonitrile. So. mp. 188-189 ° C (decomp.).

Found,%: C 37.80; H 3.21.

C6H607

Calculated,%: C 37.91; H 3.16. , IR spectrum (KBG), 3580, 3400-3000, 1770, 1720, 1690, 1590.

NMR spectrum on Н (оЈ6-DMSO), &: 69.5 (d, С in 5-position): 77.2 (d, С in 4-position), 118.9 (s, С in 2-position ), 152.3 (s, C in 3-position); 170.5 (s, C in the 1-position); 171.7 Cc, C in the 6-position).

Example 2 A mixture consisting of 2.48 g (0.01 mol) of 2.3-0-isopropylidene-2-keto-0-glucaric acid and the aqueous acid solution listed in Table 1 is stirred at 65 ° C 2 After the completion of the reaction period, the volume of the reaction mixture was adjusted to 100 ml and analyzed by liquid chromatography with high resolution (Zorbax BP-NHj column. 4-250 mm; mobile phase - a mixture of 25% 0.01 M KNrP04 and 75% acetonitrile , flow rate - 1.5 ml / min, detector - SE-31 Showa Denko). D-glucosaccharoascorbic acid obtained with the outputs presented in table 1.

Example 3. A mixture of 3.06 g (0.01 mol) of 2.3-0-cyclohexylidene--2-keto-O-glucarinic acid and 6 ml of concentrated hydrochloric acid is stirred at 70 ° C

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Yield 79.6%.

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Example 4 2,3-0-benzylide

-2-keto-B-glucarinic acid (1.48 g, 0.005 mol) was dissolved in 10 ml of 20% hydrochloric acid and the solution was stirred at 70 ° C for 1 hour. After that, the total solution was adjusted to 100%. ml and subjected to its analysis by liquid chromatography with high resolution, which shows the formation of 0.82 g of D-glucose-ascorbic acid. Yield 85.8%

Example 5. A mixture consisting of 24.9 g of unpurified syrup 2-ke TO-D-glucarinic acid (having a purity of 83.7%, as determined by high-resolution liquid chromatography, 0.10 mol), 15 ml 35 of concentrated hydrochloric acid and 150 ml of toluene are stirred at 65 ° C for 4 hours (65 ° C is the internal temperature of the reactor). Thereafter, the reaction mixture is evaporated to dryness, 1.0 g of activated carbon and 200 ml of water are added and the mixture is heated for about 5 minutes, then filtered using a glass filter. The filtrate is analyzed in the usual manner by high resolution liquid chromatography, which indicates the formation of 17.7 g of D-glucosaccharoaccorbic acid. Yield 93.3%.

The filtrate is again concentrated to dry under reduced pressure, a small amount of ether is added to the residue and the insoluble material is collected by filtration, washed with a small amount of dichloromethane and dried, and recrystallized from a mixture of acetone and benzene and 15.8% D-glucosachro-ascorbic acid is obtained. The yield is 83.1%. M.p. 188-189 ° С (decomp

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Yield 79.6%.

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Example 4. 2.3-0-Benzylidene-2-keto-B-glucaric acid (1.48 g, 0.005 mol) was dissolved in 10 ml of 20% hydrochloric acid and the solution was stirred at 70 ° C for 1 hour. After This total amount of the solution is adjusted to 100 ml and analyzed by high performance liquid chromatography, which indicates the formation of 0.82 g of D-glucosaccharo ascorbic acid. The yield is 85.8%.

Example 5. A mixture consisting of 24.9 g of crude 2-ke-TO-D-glucarinic acid syrup (having a purity of 83.7%, by definition using high-resolution liquid chromatography, 0.10 mol), 15 ml 5 concentrated hydrochloric acid and 150 ml of toluene are stirred at 65 ° C for 4 hours (65 ° C is the internal temperature of the reactor). Thereafter, the reaction mixture is evaporated to dryness, 1.0 g of activated carbon and 200 ml of water are added and the mixture is heated for about 5 minutes, then filtered using a glass filter. The filtrate is analyzed in the usual manner by high resolution liquid chromatography, which indicates the formation of 17.7 g of D-glucosaccharoascorbic acid. Yield 93.3%.

The filtrate is again concentrated to dryness under reduced pressure, a small amount of ether is added to the residue, and the insoluble matter is collected by filtration, washed with a small amount of dichloromethane and dried and recrystallized from a mixture of acetone and benzene to obtain 15.8 g of D-glucosaccharoascorbic acid. The yield is 83.1%. M.p. 188-189 ° C (decomp.)

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EXAMPLE 6 A suspension of 50.0 g of crude secondary acid 2-keto B-calcium calcium glucose hydrate (the content of secondary acid 2-keto glucose calcium – C6H609CaHNEO trihydrate is 85.1% by definition using high-performance liquid chromatography, 0, 1417 mol) in 800 ml of acetone is stirred at room temperature and at the same time, drop by drop, slowly add 17.19 g (0.17 mol) of 97% sulfuric acid. At the end of the addition, the mixture is stirred for another 10 hours. The insoluble matter is filtered off and washed with 300 ml of acetone. The filtrate and the washings were combined and evaporated to dryness under reduced pressure, 100 ml of concentrated hydrochloric acid was added to the residue, and the mixture was heated at 70 ° C for 20 minutes. The reaction mixture is evaporated to dryness under reduced pressure. 100 ml of water and 0.5 g of activated carbon are added to the residue and the mixture is heated at 70 ° C for about 5 minutes. The activated carbon is removed by filtration, and the filtrate is concentrated to dryness under reduced pressure. A mixture of ether and acetonitrile is added to the residue, the insoluble matter is collected by filtration, washed with a small amount of dichloromethane and then dried in a desiccator under reduced pressure to obtain 22.2 g of D-glucosachro-ascorbic acid monohydrate. Purity 98.8%. The yield is 74.4%. M.p. 188-18 ° C (decomp.), (Recrystallization from a mixture of acetone and benzene).

Example 7. A mixture consisting of 5 mmol of a 2,3-0-ketal salt or 2-keto-B-glucarinic acid acetal salt or 5 mmol (in total) of a mixture of these two salts and 1U ml of 15% hydrochloric acid stirred at 65 ° C for 1 hour. After this, the total volume was made up to 50 ml and analyzed by high-resolution liquid chromatography using the method described in Example 2. 2-glucosaccharobascorbic acid was obtained in the exits shown in Table 2.

Example 8. 500 g of crude secondary acidic 2-keto-B- calcium glucate (the content of secondary acidic acid 2-keto 389006

-D-calcium calcium C6H6OvSa NO3 is 85.1%, 1.417 mol) is suspended in 1500 ml of distilled water, and 214.9 g of 97% sulfuric acid (2.1255 mol) is gradually added to the suspension with shaking and room temperature. At the end of the addition, the mixture is left overnight with Yu stirring at room temperature. The insoluble matter is collected by filtration and washed with 100 ml of distilled water. Wash water is mixed with the filtrate. The filtrate obtained in this way is discharged.

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The mixture is kept under reduced pressure at a base at 55 ° C until the concentrate remains 300 ml. After cooling, the insoluble material is filtered off. The filtrate is heated in a water bath for 8 hours at 55 ° C and concentrated under reduced pressure. 200 ml of distilled water is added to the concentrate and the insoluble matter is filtered off. The solution thus obtained is passed through a column filled with activated carbon (300 ml Shirasagi activated carbon, special purity for chromatography, manufactured and supplied by Takeda Chemicalio Ltd) with the aid of water. Elution is carried out using distilled water. The extract is concentrated under reduced pressure, and the precipitated crystals are collected by filtration, dried, and receive raw crude crystals. The filtrate is passed through a column filled with activated carbon. The eluate is concentrated under reduced pressure, and the precipitated crystals are collected by filtration, dried, and secondary crude crystals are obtained. The filtration is carried out further in the manner described above, and tertiary raw crystals are obtained. These crystals are mixed with the primary and secondary output of the crystals, thus obtaining 247 g of crude monohydrate of D-glucosaccharoscorbic acid. Purity 81.1%.

Pure D-glucosaccharoascorbic acid monohydrate is obtained by recrystallization of crude D-glucosaccharoascorbic acid monohydrate from distilled water. M.p. 134-138S.

Found,%: C 34.52; H 3.89

s.nvoy

Calculated,%: C 34.63; H 3.87. IR Spectrum (KBG), 3580, 3500, 3400-3000, 1700, 1720, 1690, 1590.

As a method of removing crystallization water from D-glucosaccharoascorbic acid monohydrate, recrystallization from an anhydrous organic solvent and drying under reduced pressure can be mentioned. Azeotropic dehydration is alternatively applicable and is performed as follows.

To 10 g of D-glucosaccharoascorbic acid monohydrate, 100 ml of acetonitrile are added. Distillation of acetonitrile is continued at ordinary pressure using a distillation apparatus, a quantity of acetonitrile equal to distilled acetonitrile is continuously introduced into the apparatus. A total of 250 ml of acetonitrile was distilled. As the acetonitrile is distilled, the anhydrous D-glucose sugar-ascorbic acid begins to precipitate. After distillation, the precipitate is collected by filtration, dried, and 8.8 g of D-glucose sugar-ascorbic acid are obtained. The yield is 96.3%.

This product was completely identical in m. IR-NMR-1 H-, NMR-1 C spectra and wake-up time in high resolution liquid chromatography.

Note 9. A mixture consisting of 12.2 g of crude 2-keto-O-glucaric acid syrup (with a purity of 85.4%, as determined by HPLC; 0.05 mol), 1.0 ml of trifluoroacetic acid and 20 ml distilled water, stirred at 65 ° C (temperature inside the reactor) for 5 hours. After that, the reaction mixture was concentrated to dryness, 0.5 g of active carbon and 50 ml of distilled water were added, and then filtered through a glass filter. The obtained filtrate is analyzed by a conventional method using HPLC, which shows a yield of 8.42 g of D-glucosaccharoascorbic acid. Yield 88.6%.

Example 1U. A mixture consisting of 6.0 g of syrup of raw 2-keto-D-glucarinic acid (purity 85.4%, which is installed 24.6 mm), 15 ml of ion exchange resin in H + -form (IR-120 V) and 50 ml distil

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water is stirred at 50 ° C (temperature inside the reactor) for 4 hours. Thereafter, the ion exchange resin is removed by filtration. To the resulting filtrate, 0.2 g of active carbon was added and the mixture was heated for 3 minutes, then the active carbon was removed by filtration through a glass filter. The filtrate is analyzed by a conventional method using HPLC, which shows the recovery of 4.27 g of D-glucosaccharoascorbic acid. Yield 91.3%.

Example 11. A mixture consisting of 6.0 g of a crude syrup of 2-keto-O-glucaric acid (with a purity of 85.4%, as established by HPLC, 24.6 mm), 5 ml of concentrated HCl and 5 ml of distilled water, stirred under ice cooling for 7 hours. The reaction mixture is concentrated under reduced pressure, keeping the temperature below. 0.1 g of active carbon and 30 ml of distilled water are added to the resulting precipitate, after which the mixture is stirred at room temperature for 10 minutes and then active carbon is removed through a glass filter to obtain a yellow filtrate. 0 The filtrate is analyzed in a traditional manner using HPLC, which shows the production of 3.9 g of D-glucosaccharoascorbic acid. The output of 83.8%.

Example 12. A mixture consisting of 10 g of crude 2-keto-p-glucurinic acid syrup (purity 85.4%, as established by HPLC; 41 mm), 1 ml of concentrated HC1 and 40 mL of diethylene glycol dimethyl ether stirred in an oil bath at 150 ° C (oil bath temperature) for 30 minutes. After that, 1.5 g of barium hydroxide and 50 ml of distilled water are added to the reaction mixture, then the mixture is stirred for another 30 minutes. Insoluble materials are collected by filtration, then washed with a small amount of distilled water. The filtrate is concentrated under reduced pressure and 100 ml of distilled water is added to it. The analysis is carried out by a conventional method using HPLC,. which shows the production of 5.65 t D-glucosaccharoascorbic acid. . Output 72.5%.

Example 13. A solution of 1.0 g (5.26 mmol) of D-glucosaccharoascorbic acid in 10 ml of distilled water is passed through a column filled with cation-exchange resin (30 ml of resin, Na-form, Dowex 50 W-X8 brand from Dow Chemical , USA). The washing is carried out with distilled water and 400 ml of the extract are obtained. This extract is evaporated under reduced pressure and 10 ml of methanol is added to the residue, and the mixture is left under stirring overnight. The precipitate is collected by filtration, dried in a desiccator, and 0.57 g of monosubstituted sodium D-glucosaccharosorbate is obtained. Yield 45.3%. Mp about 170 ° C (decomp.).

Found,%: C 30.38; H 3.21.

С6Н5СЦМа-.1НгО

Calculated,%: C 30.14; H 3.37.

IR Spectrum (KBG), cm 1: 3600-2800, 1750, 1680, 1620, 1420.

Example 14. D-glucose-ascorbic acid (1.90 g, 0.01 mol) was added to 30 ml of distilled water and the mixture was stirred at room temperature. To the resulting aqueous solution, 1.06 g (0.01 mol) of sodium carbonate is added and the mixture is kept stirring until the evolution of carbon dioxide ceases. The resulting reaction mixture is added to 200 ml of methanol. The resulting precipitate was collected by filtration, dried, and 2.50 g of disubstituted D-glucoharco ascorbate sodium was obtained. The yield is 99.2%. M.p. 185 ° C (dec,).

Found,%: C 28.67, H 2.61.

CfeH407NaЈHj, 0

Calculated,%: C, 28.59; H 2.40.

Example 15. A solution of 1.0 g (5.26 mmol) of D-glucosaccharoascorbic acid in 10 ml of distilled water is passed through a column filled with 100 ml of cation-exchange resin (brand JP-1208, K-form, from Rohm and Haas.). The washing is carried out with distilled water and 400 ml of extract with a pH of 5.17 is obtained. The extract was concentrated under reduced pressure, and 400 ml of methanol was added to the residue, the resulting precipitate was collected by filtration, dried in a desiccator under reduced pressure. 1.12 g of monosubstituted potassium D-glucoharcoascorbate is obtained. The yield is 83.5%. M.p. (different).

Found: C 28.10J H 2.83, C6HffOrK "1.5 Hg.0. Calculated,%: C 28.24: H 3, T6. IR spectrum (KBG), 3600-2800, 1760, 1660, 1600.

Example 16. D-glucose-ascorbic acid (1.90 g, 0.01 mol) was added to 30 ml of distilled water and the mixture was stirred at room temperature. 1.38 g (0.01 mol; potassium carbonate is added to the resulting aqueous solution and the mixture is stirred until carbon dioxide formation ceases. The resulting reaction mixture is added dropwise to 300 ml of methanol. The precipitate is collected by filtration, dried at 2.70 g of disubstituted potassium D-glucosaccharo ascorbate is obtained under reduced pressure. The yield is 95.0%, mp. 175 ° C (decomp.).

Found%: C 25.23, H 2.31. C6H50 -K O

Calculated,%: C 25.35; H 2.13. IR spectrum (KBG), cm 1: 3600-2900, 1720, 1590, 1400.

Example 17. A solution of 1.0 g (5.26 mmol) of D-glucosaccharoascorbic acid in 10 ml of distilled water is passed through a column filled with 30 ml of ion-exchange resin in Ca + form (Dowex 50W-X8, Dow Chemical, USA). The elution is carried out with distilled water and 400 ml of the extract are obtained with a pH of 3.5. This extract is concentrated under reduced pressure, 20 ml of acetone is added to the residue, the resulting precipitate is collected by filtration, dried in a desiccator under reduced pressure, and 0.96 g of monosubstituted D are obtained - glucose sugar calcium. Yield 81.6%. M.p. 190-205 ° C (decomp.). Found,%: C 32.13, H 3.19. C6H5071 / 2Ca 0.8 H, .0 Calculated,%: C 32.27; H 2.98 IR spectrum (KBG), 3600-2800, 1760, 1680, 1600.

Example 18 D-glucosaccharoascorbic acid (1, PPO g, 0.01 mol; added to 30 ml of distilled water and the mixture was stirred at room temperature. To the resulting aqueous solution was added 0.741 g (0.01 mol) of hydroxide

Calcium and after 30 minutes, the resulting precipitate is collected by filtration, dried under reduced pressure, and 2.2 g of secondary acidic D-glucose charcoascine calcium are obtained. The yield is 78%. M.p. (different).

Found,%: C 25.23; H 3.84.

С6Н40 -Са-ЗНаО

Calculated,%: C, 25.23 H, 3.57.

Example 19. The study of anti-oxidative activity.

0.4 g of D-gloxosaccharoascorbic acid is dissolved in ethanol;

the tuna is immersed in a 1.0% aqueous solution of sodium L-ascorbate. The results are presented in table 4.

Claims (2)

1. A method for producing D-glucosaccharo ascorbic acid or a salt thereof, characterized in that 2-keto-B-glucaric acid or its 2, J-0-acetal or ketal is treated, acetal or ketal part of which is represented by the formula adjusted to 50 ml; 1.5 part tuna is obtained and another post part improves the quality of fats and oils or products containing oils and fats. To 20 ml of each sample of soybean oil (peroxide value equal to 20 2.85 meg / kg, then given in the reduction as IF), respectively, add 0.5 ml of I, which improves the quality of the products, ethanolic solution of D-ascorbic acid and dibutyl alcohol. 25 of Sitoluene (LOT), as shown in Table 3. These samples are subjected to oxidation by means of an experimental device for determining the stability of fats and 30 oils (AOM-device manufactured by Kuramochi Kagaku Kikai Seisakusho, Ltd.) at 97.8 and 1.0 ° C with aeration at a rate of 2.33 mp / s, then a bootleg - the corresponding IF is timed out. The results are obtained in the form of a curve showing the change in the peroxide number of soybean oil containing various additives. The stability of fats and oils is expressed in terms of the time during which the peroxide value becomes constant and the longer the time, the more stable the sample. Until the corresponding peroxide numbers reached 100 meg / kg, for L-ascorbic acid (experiment 2) it will take 20 hours, for dibutyloxytoluene (experiment 3) consumption-Os Ri - (, 35 where R, and Kr are the same or different and represent hydrogen, lower alkyl, phenyl or R. and R form a cyclohexylidene group, in free form, in aqueous solution or in suspension with a neutral organic solvent at 0-150 ° C, followed by isolation of the free state by the known methods of the desired product or in the form of a salt of alkali or alkaline earth metals. 2. A process according to claim 1, characterized in that mineral acid, organic acid or ion exchange resin in the H-form is used as the acid. lasts 11 hours, while for an agent according to the invention (experiment 1) it takes 28 hours. Thus, the agent according to the invention shows a higher antioxidant effect in comparison with conventional antioxidants. Example 20. The lean part of tuna is cut to 1 ,, cm and immersed for 2 minutes in a 1% solution of disubstituted sodium D-glucosaccharoacorbinate in water, then stored in a refrigerator for 21 hours. The change in color is observed with the naked eye. The control is the raw post. the tuna is immersed in a 1.0% aqueous solution of sodium L-ascorbate. Rezul. tats are presented in table 4. Invention Formula 1. A method for producing D-glucosaccharo ascorbic acid or a salt thereof, characterized in that 2-keto-B-glucaric acid or its 2, J-0-acetal or ketal is treated, acetal or ketal part of which is represented by the formula part of tuna and another post part - (, where R, and Kr are the same or different and represent hydrogen, lower alkyl, phenyl or R. and R form a cyclohexylidene group, in free form, in aqueous solution or in suspension with a neutral organic solvent at 0-150 ° C, followed by isolation of the free state by the known methods of the desired product or in the form of an alkali or alkaline earth metal salt. 2. A process according to claim 1, characterized in that mineral acid, organic acid or ion exchange resin in the H-form is used as the acid. 13 Acid (10 ml) 153890014 Table 1 The output of the D-glukosaharoaskorbin acids, 15 Table Experiment 2 3 Additive Color change after 21 hours D-glucosaccharo ascorbine acid L-ascorbine acid Dibutyloxytoluene No additive ------- Treatment with add-on weight ratio to the volume of y --- Disubstituted D-glu- No change Kosaharoascorbate .l sodium Without additive (control) 0.02 0.02 0.02 Half of the lean part of the darkened L-ascorbate sodium Quarter hour 15 the lean part is darkened 3 sixteen Table 4 Color change after 21 hours Without additive (control) Sodium L-ascorbate 15 the lean part is darkened