JP5787309B2 - Method for producing D-tartaric acid or a salt thereof - Google Patents

Description

  The present invention relates to a method for producing D-tartaric acid or a salt thereof from 4-keto-D-arabonic acid or a salt thereof.

  D-tartaric acid and salts thereof are organic compounds having optical activity and are used as raw materials for optical resolution agents and asymmetric compounds in the production of pharmaceuticals and agricultural chemicals, and industrially as raw materials for D-tartaric acid derivatives. It is an important substance that is widely used.

  As a method for producing D-tartaric acid, for example, D-tartaric acid is selectively collected according to the difference in crystal form of DL-tartaric acid obtained by chemically racemizing L-tartaric acid produced as a by-product during wine production. Chemical resolution method (Patent Documents 1 to 3, Non-Patent Documents 1 and 2), DL-tartaric acid is converted to a catabolic substance using a dehydrase that specifically reacts only with L-tartaric acid, and D-tartaric acid is converted from the remaining components. Enzymatic method (Patent Document 4), and selective fermentation method (Patent Document 5) where L-tartaric acid is selectively assimilated by a fermentation method using DL-tartaric acid as a carbon source and residual D-tartaric acid is collected. ), A method of producing D-tartaric acid by allowing a D-form specific hydrolase to act on cis-epoxysuccinic acid obtained by chemical synthesis from benzene as a petroleum component (Patent Document 6).

Soviet Patent No. 694492 JP 59-55851 A JP 59-29636 A Japanese Patent Laid-Open No. 50-24490 Japanese Patent Publication No.8-17718 JP-A-8-245497

R. Li, “Yiyao Gongye”, (USSR), 1988, 19, p. 442 Moskovets et al., “Deposited Dot. VINITI” (Soviet Union), 1983, p. 81-83

  Conventionally, DL-tartaric acid using L-tartaric acid as a raw material and cis-epoxysuccinic acid using crude oil as raw materials have been used as substrate raw materials in the production of D-tartaric acid, but it is efficient to use cheaper substrate raw materials. There is a need for production of high purity D-tartaric acid.

  The present invention is a method for producing D-tartaric acid or a salt thereof from 4-keto-D-arabonic acid or a salt thereof in a high yield and a high yield, and is highly practical for use in industrial production. It is to provide a method.

  As a result of intensive studies to solve the above problems, the present inventors can efficiently produce D-tartaric acid or a salt thereof from 4-keto-D-arabonic acid or a salt thereof at a low cost. The optimum condition for a highly practical method that can be used for industrial production has been found, and the present invention has been completed.

  That is, the present invention is a method for producing D-tartaric acid or a salt thereof from 4-keto-D-arabonic acid or a salt thereof, wherein a carbonate is added to an aqueous solution containing 4-keto-D-arabonic acid or a salt thereof. The present invention provides a method for producing D-tartaric acid or a salt thereof, which comprises aerobically contacting to produce D-tartaric acid or a salt thereof in a reaction solution.

  According to the present invention, D-tartaric acid or a salt thereof can be produced efficiently and at low cost by aerobically contacting a carbonate with 4-keto-D-arabonic acid or a salt thereof. Furthermore, D-tartaric acid or a salt thereof can be more efficiently produced by bringing a carbonate and a transition metal compound having a catalytic function into contact at the same time. Therefore, the production method of the present invention can be used for industrial production, and is extremely practical.

  Hereinafter, embodiments of the present invention will be described in detail. That is, 4-keto-D-arabonic acid which is a substrate in the present embodiment refers to free 4-keto-D-arabonic acid, and salts thereof include potassium salt of 4-keto-D-arabonic acid. , Sodium salts, calcium salts, ammonium salts and the like.

  The concentration of 4-keto-D-arabonic acid or a salt thereof as the substrate in the present embodiment is not particularly limited, but is preferably in the range of 5 to 15% (w / v), and 5 to 10% (w / v). More preferably, it is the range.

  In this embodiment, carbonates such as potassium, sodium, calcium, and ammonium can be used as the carbonate to be brought into contact with 4-keto-D-arabonic acid or a salt thereof.

  In addition, the carbonate concentration in the present embodiment is preferably in the range of 0.005 to 1.5M and in the range of 0.5 to 1M from the viewpoint of improving the yield of D-tartaric acid or its salts. More preferred.

  In the reaction, from the viewpoint of improving the yield of D-tartaric acid or a salt thereof, the pH is preferably in the range of 8 to 12, and particularly preferably in the range of pH 9 to 11.

  For the pH adjustment, an acid solution such as hydrochloric acid, sulfuric acid or nitric acid or an alkaline solution such as sodium hydroxide, potassium hydroxide, calcium hydroxide or ammonia can be used.

  The acid solution and the alkali solution can be added before the reaction and / or during the reaction.

  From the viewpoint of improving the yield of D-tartaric acid or a salt thereof, the reaction temperature in the present embodiment is preferably in the range of 15 to 60 ° C, and more preferably in the range of 15 to 40 ° C.

  The reaction in the present embodiment must be performed under aerobic conditions. When a small reactor such as a flask is used, the reaction vessel is attached by a stopper having good air permeability and is reciprocally or rotationally shaken. When a large reaction tank such as a reaction tank is used, stirring is performed while supplying air or oxygen.

  In this embodiment, when the reaction is carried out under the above conditions, the reaction is completed in 1 to 5 days, preferably 1 to 3 days, and D-tartaric acid or a salt thereof can be produced with high efficiency.

  In this embodiment, the 4-keto-D-arabonic acid or a salt thereof is aerobically contacted with a carbonate and a transition metal compound having a catalytic function, whereby a better D-tartaric acid or a salt thereof is obtained. Since conversion efficiency is obtained, it is particularly preferable.

  The transition metal compound may be a transition metal such as copper, manganese, nickel, iron and other water-soluble metal compounds such as sulfate, nitrate, carbonate, acetate, copper oxide, manganese oxide. Insoluble metal compounds such as iron oxide can also be used. In particular, the insoluble metal compound can be easily recovered by centrifugation after the completion of the reaction, and the recovered insoluble metal compound can be used again for the reaction.

  The addition amount of the transition metal compound in the present embodiment is preferably in the range of 0.0001 to 2% (w / v) with respect to the reaction solution from the viewpoint of improving the yield of D-tartaric acid or its salts. , 0.001 to 1% (w / v) is more preferable.

  In the present embodiment, the carbonate concentration in the presence of the transition metal compound is preferably in the range of 0.005 to 1.5M, from the viewpoint of improving the yield of D-tartaric acid or its salts, The range of 0.0M is more preferable, and the range of 0.3 to 0.5M is more preferable.

  In this embodiment, when the carbonate and the transition metal compound are brought into aerobic contact with the 4-keto-D-arabonic acid or a salt thereof, the reaction is completed within 1 to 4 days, preferably 1 to 2 days. It is possible to produce D-tartaric acid or a salt thereof with higher efficiency.

  Furthermore, the method for purifying D-tartaric acid or its salts from the reaction solution obtained above is not particularly limited, but for example, potassium D-tartaric acid (also referred to as D-tartaric acid monopotassium salt) with respect to water. It can be easily purified by using a general method utilizing the poorly soluble nature.

  That is, the reaction solution is separated into a centrifugal supernatant and an insoluble component by centrifugation. Note that since the recovered insoluble component contains a transition metal compound, it can be used again for the reaction.

  On the other hand, D-potassium hydrogen tartrate can be obtained as a precipitate by adding an inorganic acid such as hydrochloric acid to the centrifugal supernatant and lowering the pH to a range of 3.5 to 4.0. Further, in order to increase the recovery rate of D-potassium hydrogen tartrate, it is preferable to store it at a low temperature.

  The precipitate containing D-potassium hydrogen tartrate obtained in the above step can be recovered by a method such as centrifugation or filtration.

  The recovered precipitate is suspended in a small amount of water and dissolved while adding 5 M potassium hydroxide as an alkaline solution, and then the remaining insoluble transition metal compound and the like are removed again by centrifugation. A centrifugal supernatant can be obtained.

  By adding an inorganic acid such as hydrochloric acid to the centrifugal supernatant as described above, the pH is lowered to a range of pH 3.5 to 4.0, and kept at a low temperature (for example, 5 ° C.) overnight, whereby D-tartaric acid is obtained. Recrystallization of potassium hydrogen salt can be performed efficiently. Moreover, the purity of D-hydrogen tartrate potassium salt can be improved by repeating these operations.

  The crystals of potassium D-tartrate can be recovered by centrifugation, and the recovered crystals can be dried under vacuum and reduced pressure to obtain highly pure potassium potassium tartrate.

Furthermore, when the potassium D-tartrate is suspended in water and the pH is adjusted to 7-8 by adding a potassium hydroxide solution while stirring, it becomes water-soluble D-potassium tartrate, which is converted to an H ⁺ type cation. After passing through the column filled with the exchange resin, the column can be further washed with deionized water to recover the non-adsorbed fraction and the washing solution that have passed through the column.

  The recovered liquid is concentrated under reduced pressure at 35 ° C., and the resulting paste-like concentrate is dissolved in a small amount of ethanol, and this is retained in a refrigerator at 5 ° C. to precipitate free D-tartaric acid crystals. it can.

  Moreover, the said crystal | crystallization is collect | recovered by centrifugation, A high purity free type D-tartaric acid can be obtained by vacuum-drying this.

  In this embodiment, 4-keto-D-arabonic acid and tartaric acid are quantified by the high-performance liquid chromatography (hereinafter referred to as HPLC) method (Herrmann et. Al, Appl. Microbiol. Biotechnol., 64) reported by Herrmann et al. 86-90, 2004) can be used, but it is more preferable to analyze by a quantitative method obtained by improving the method. The improved quantitative method is shown below.

  The improved quantitative method uses a Shodex RSpak DE-613 column (6.0 mm inner diameter × 150 mm length, manufactured by Shodex Co.) as a column, and 0.5 ml of 9 mM perchloric acid solution as a mobile phase solvent per minute. Quantitative calculation is performed by detecting with an ultraviolet (UV) detector having a wavelength of 210 nm and recording the peak with a recorder. Under these conditions, 4-keto-D-arabonic acid has a retention time of 7.71 minutes and D-tartaric acid has a retention time of 8.76 minutes.

  In the present embodiment, 4-keto-D-arabonic acid and D-tartaric acid in the reaction solution are quantified by measuring the peak areas of the respective samples with known concentrations of 4-keto-D-arabonic acid and D-tartaric acid standard solution. The concentration is calculated by comparing with the peak area.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to a following example.

1. Examination of concentration of dipotassium carbonate-potassium hydrogen carbonate solution 0.0005M, 0.005M, 0.05M, 0.1M, 0.3M, 0.5M, 1 containing 277 mg potassium 4-keto-D-arabonate The reaction was started by preparing in a 100 ml Erlenmeyer flask so that the total amount of 0.0M or 1.5M (final concentration) dipotassium carbonate-potassium bicarbonate solution (pH 10.0) was 3 ml. Further, the reaction was carried out at 30 ° C. with aerobic stirring at 220 rotations per minute. For control, distilled water was used in place of the dipotassium carbonate-potassium bicarbonate solution, and the mixture was adjusted to pH 10.0 with a 5M potassium hydroxide solution. 48 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and D-tartaric acid contained in the diluted solution was quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Moreover, the result converted into D-tartaric acid density | concentration in a reaction liquid is shown in Table 1.

  As shown in Table 1, when a 1.0 M dipotassium carbonate-potassium hydrogen carbonate solution (pH 10.0) was used, the amount of D-tartaric acid produced was the maximum, and 11.3 g / L (molar yield). 16.5%).

2. Study of transition metal compound added to dipotassium carbonate-potassium hydrogen carbonate solution 277 mg of potassium 4-keto-D-arabonate and 0.01% (w / v) powdered copper oxide (II) (Sigma), Basic copper carbonate (II) monohydrate (Wako Pure Chemical Industries), manganese sulfate (II) pentahydrate (Wako Pure Chemical Industries), powdered manganese oxide (IV) (Sigma), nickel sulfate (II) 0.3M (final concentration) containing hexahydrate (Wako Pure Chemical Industries, Ltd.), iron (III) sulfate n hydrate (Wako Pure Chemical Industries, Ltd.) or iron (II) sulfate hexahydrate (Wako Pure Chemical Industries, Ltd.) ) The reaction was started by preparing in a 100 ml Erlenmeyer flask so that the total amount of dipotassium carbonate-potassium bicarbonate solution (pH 10.0) was 3 ml. The reaction was carried out at 28 ° C. with 220 rotations per minute with aerobic stirring. The case where no transition metal compound was added was used as a control. 46 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Table 2 shows the results converted to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 2, in all cases of the seven transition metal compounds tested, the D-tartaric acid concentration in the reaction solution was higher than that in the case of no addition (control). In particular, the addition of a copper compound, a manganese compound or an iron compound was effective in producing D-tartaric acid.

3. Examination of concentration of copper (II) oxide added to dipotassium carbonate-potassium bicarbonate solution 277 mg of potassium 4-keto-D-arabonate and 0.0001% (w / v), 0.001% (w / v ), 0.01% (w / v), 0.05% (w / v), 0.1% (w / v), 0.5% (w / v), 1.0% (w / v) ) Or 2.0% (w / v) powdered copper oxide (II) (Sigma) 0.3M (final concentration) dipotassium carbonate-potassium bicarbonate solution (pH 10.0) is 3 ml in total. Thus, the reaction was started in a 100 ml Erlenmeyer flask. The reaction was carried out at 28 ° C. with 220 rotations per minute with aerobic stirring. In addition, the case where the powdered copper oxide (II) was not added was used as a control. 44 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Table 3 shows the results of conversion to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 3, in all cases where copper (II) oxide (powder) was added, the D-tartaric acid concentration in the reaction solution was higher than that in the case of no addition (control). In particular, in the case of 0.01% (w / v) addition, 23.6 g / L (molar yield is 34.4%), and in the case of 0.05% (w / v) addition, 21.9 g / L. (Molar yield was 31.9%) and was effective in producing D-tartaric acid.

4). Conversion to D-tartaric acid with copper (II) oxide alone 277 mg of potassium 4-keto-D-arabonate and 0.0001% (w / v), 0.001% (w / v), 0.01% ( w / v), 0.05% (w / v), 0.1% (w / v), 0.5% (w / v), 1.0% (w / v) or 2.0% ( Prepared in a 100 ml Erlenmeyer flask so that the total volume of distilled water (w / v) powdered copper oxide (II) (Sigma) adjusted to pH 10.0 with 5M potassium hydroxide solution was 3 ml. The reaction started. The reaction was carried out at 28 ° C. with 220 rotations per minute with aerobic stirring. The case where no powdered copper oxide (II) was added was used as a control. 48 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Table 4 shows the results converted to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 4, in the absence of carbonate, almost no catalytic effect by copper (II) oxide was observed, and the D-tartaric acid concentration in the reaction solution was 0.5 to 1.8 g / L (molar yield). The rate was 0.7 to 2.6%. From this result, it was found that the conversion efficiency of 4-keto-D-arabonic acid to D-tartaric acid was low with copper (II) oxide alone.

5. Study of carbonate 0.3M (final concentration) dipotassium carbonate-carbonate containing 277 mg potassium 4-keto-D-arabonate and 0.01% (w / v) powdered copper (II) oxide (Sigma) Total amount of potassium hydrogen solution (pH 10.0), 0.3 M (final concentration) disodium carbonate-sodium hydrogen carbonate solution (pH 10.0) or 0.3 M (final concentration) diammonium carbonate-ammonia solution (pH 10.0) Was prepared in a 100 ml Erlenmeyer flask so as to be 3 ml, and the reaction was started. The reaction was carried out at 28 ° C. with 220 rotations per minute with aerobic stirring. 48 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Table 5 shows the results of conversion to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 5, D-tartaric acid was produced in all cases tested, especially high in the case of dipotassium carbonate-potassium bicarbonate and in the case of disodium carbonate-sodium bicarbonate.

6). Examination of dipotassium carbonate-potassium bicarbonate concentration in the presence of powdered copper oxide (II) 277 mg potassium 4-keto-D-arabonate and 0.01% (w / v) powdered copper oxide (II) (Sigma) 0.0005M, 0.005M, 0.05M, 0.1M, 0.3M, 0.5M, 1.0M or 1.5M (final concentration) dipotassium carbonate-potassium bicarbonate solution (pH 10. The reaction was started by preparing in a 100 ml Erlenmeyer flask so that the total amount of 0) was 3 ml. The reaction was carried out at 28 ° C. with 220 rotations per minute with aerobic stirring. For control, distilled water was used in place of the dipotassium carbonate-potassium bicarbonate solution, and the mixture was adjusted to pH 10.0 with a 5M potassium hydroxide solution. 48 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Table 6 shows the result of conversion to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 6, when the concentration of dipotassium carbonate-potassium bicarbonate solution (pH 10.0) is 0.3 to 0.5 M, the D-tartaric acid concentration in the reaction solution is 20.3 to 22.9 g. / L (yield was 29.6 to 33.4 mol%), which was a particularly high value.

7). Examination of pH of dipotassium carbonate-potassium bicarbonate solution in the presence of copper (II) oxide 277 mg potassium 4-keto-D-arabonate and 0.01% (w / v) powdered copper (II) oxide ( 100 ml so that the total amount of 0.3 M (final concentration) dipotassium carbonate-potassium bicarbonate solution (pH 8.00, 9.00, 10.0, 11.0 or 12.0) containing Sigma is 3 ml. The reaction was started by preparing in a conical flask. The reaction was carried out at 28 ° C. with 220 rotations per minute with aerobic stirring. 48 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Table 7 shows the result of conversion to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 7, D-tartaric acid was produced at 16.2 to 23.6 g / L (molar yield of 23.6 to 34.4%) at all tested pHs, particularly at pH 10.0. The highest value was shown.

8). Temperature Study 0.3 M (final concentration) dipotassium carbonate-bicarbonate containing 277 mg potassium 4-keto-D-arabonate and 0.01% (w / v) powdered copper (II) oxide (Sigma) The reaction was started by preparing in a 100 ml Erlenmeyer flask so that the total amount of potassium solution (pH 10.0) was 3 ml. The reaction was carried out at 15 ° C., 28 ° C., 40 ° C. or 60 ° C. with 220 rotations per minute with aerobic stirring. 44 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Table 8 shows the result of conversion to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 8, D-tartaric acid was produced at 11.5 to 23.6 g / L (molar yield: 16.8 to 34.4%) at all temperatures tested, particularly at a reaction temperature of 28 ° C. In this case, the highest value was 23.6 g / L (the yield was 34.4 mol%).

9. Presence of oxygen 0.3M (final concentration) dipotassium carbonate-hydrogen carbonate containing 277 mg of potassium 4-keto-D-arabonate and 0.01% (w / v) powdered copper oxide (II) (Sigma) The reaction was started by preparing in a 100 ml Erlenmeyer flask so that the total amount of potassium solution (pH 10.0) was 3 ml. The reaction was carried out at 28 ° C. with 220 rotations per minute with stirring in an air atmosphere or a nitrogen gas atmosphere. 48 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Table 9 shows the result of conversion to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 9, 23.6 g / L (molar yield of 34.4%) of D-tartaric acid was produced under an air atmosphere, while no D-tartaric acid was produced under a nitrogen gas atmosphere. .

10. Substrate concentration studies 5% (w / v), 7.5% (w / v), 10% (w / v) or 15% (w / v) potassium 4-keto-D-arabonate and 0. 100 ml volume so that the total amount of 0.3 M (final concentration) dipotassium carbonate-potassium bicarbonate solution (pH 10.0) containing 01% (w / v) powdered copper oxide (II) (Sigma) is 3 ml. The reaction was started by preparing in an Erlenmeyer flask. The reaction was carried out at 28 ° C. with 220 rotations per minute with aerobic stirring. 48 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. Table 10 shows the result of conversion to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 10, 14.2 to 30.7 g / L of D-tartaric acid (23.6 to 34.4% molar yield) was produced at all concentrations tested.

11. Examination with Tris / HCl solution D-Tartaric acid has the same buffering ability as the presence or absence of carbonate and dipotassium carbonate-potassium bicarbonate solution (pH 9.5) consisting of carbonate and does not contain carbonate. Using Tris / HCl solution (pH 9.5), the production of D-tartaric acid in the presence or absence of powdered copper oxide (II) was examined.

  That is, in the presence of powdered copper oxide (II), 0 containing 277 mg of potassium 4-keto-D-arabonate and 0.01% (w / v) of powdered copper oxide (II) (Sigma) .3M (final concentration) dipotassium carbonate-potassium hydrogen carbonate solution (pH 9.5) or 0.75M (final concentration) Tris / HCl solution (pH 9.5) in a 100 ml Erlenmeyer flask so that the total amount becomes 3 ml. Prepared and started reaction.

  On the other hand, in the absence of powdered copper (II) oxide, a 0.3 M (final concentration) dipotassium carbonate-potassium bicarbonate solution (pH 9.5) containing 277 mg of potassium 4-keto-D-arabonate or The reaction was started by preparing in a 100 ml Erlenmeyer flask so that the total amount of 0.75M (final concentration) Tris.HCl solution (pH 9.5) was 3 ml.

  These reactions were carried out at 28 ° C. with stirring at 220 revolutions per minute. In addition, distilled water was used as a control, and the mixture was adjusted to pH 9.5 with a 5M potassium hydroxide solution. 48 hours after the start of the reaction, the reaction solution was diluted 51 times with 9 mM perchloric acid, and the diluted solution was centrifuged at 10,000 rpm for 10 minutes, and D-tartaric acid contained in the centrifugal supernatant was removed. Quantified by HPLC. At this time, quantification was performed based on a D-tartaric acid standard solution having a concentration of 1 g / L. In addition, Table 11 shows the results converted to the D-tartaric acid concentration in the reaction solution.

  As shown in Table 11, when a Tris.HCl solution was used, in the absence of powdered copper oxide (II), 1.9 g / L (molar yield 2.8%), in the presence of powdered copper oxide (II) Produced 9.1 g / L (molar yield: 13.3%) of D-tartaric acid. On the other hand, in the case of dipotassium carbonate-potassium hydrogen carbonate solution, D-tartaric acid is 6.5 g / L (molar yield 9.5%) in the absence of powdered copper oxide (II), and powdered copper (II) oxide is present. Below, 22.5 g / L (molar yield 32.8%) of D-tartaric acid was produced, which was higher than the respective values when using the Tris.HCl solution.

12 Purification and identification of D-tartaric acid 0.3 M (final concentration) dicarbonate containing 923 mg potassium 4-keto-D-arabonate and 0.01% (w / v) powdered copper (II) oxide (Sigma) The reaction was started by preparing in a 300 ml Erlenmeyer flask so that the total amount of potassium-potassium bicarbonate solution (pH 10.0) was 10 ml. The reaction was carried out at 28 ° C. with 220 rotations per minute with aerobic stirring. In addition, 45 hours after the start of the reaction, a part of the reaction solution was diluted 51 times with 9 mM perchloric acid, and this diluted solution was centrifuged at 10,000 rpm for 10 minutes and contained in the centrifuged supernatant. When D-tartaric acid was quantified by HPLC, 23.5 g / L (molar yield: 34.3%) of D-tartaric acid was produced.

  The reaction solution was centrifuged at 10,000 rpm at 10 ° C. for 10 minutes to obtain a centrifuged supernatant. Further, 6M hydrochloric acid was gradually added to the centrifugal supernatant to pH 3.7, and when a precipitate was formed, it was kept overnight in a refrigerator at 5 ° C.

  The cold aqueous solution containing the precipitate was centrifuged at 10,000 ° C. for 10 minutes at 5 ° C., and separated into a precipitate and a supernatant. In addition, after confirming by HPLC that the target D-tartrate is contained in the precipitate, 5M potassium hydroxide solution is added to the precipitate and adjusted to pH 12, and this is dissolved again. Centrifugation was performed at 10,000 rpm for 10 minutes to remove fine particles.

  To the centrifugal supernatant, 6M hydrochloric acid was gradually added again to adjust the pH to 3.7, and when a precipitate was formed, it was kept in a refrigerator at 5 ° C. overnight.

  The precipitate was collected with a glass filter and pulverized, followed by vacuum drying at room temperature for 4 hours to obtain 221 mg (94% recovery rate) of white powder of potassium D-tartrate.

In addition, an accurate 1 g / L aqueous solution was prepared using the white powder, and this was analyzed by HPLC. The detected peak coincided with the retention time of D-tartaric acid, and the purity was 99.7%. I found out. Further, 200 mg of the above white powder was dissolved in water, and this was passed through a column packed with 50 ml of Urbanlite CG120 cation exchange resin (H ⁺ type, manufactured by Rome & Haas). Further, the column was washed with deionized water, and the non-adsorbed fraction and the washing solution that passed through the column were collected.

  The recovered liquid was concentrated under reduced pressure at 35 ° C., and the obtained paste-like concentrate was dissolved in a small amount of ethanol at 50 ° C., and this was kept in a refrigerator at 5 ° C. for 2 to 3 days. Obtained.

  The crystals were collected by centrifugation and vacuum-dried for 4 hours to obtain 57 mg of crystals.

  By the way, since there are two asymmetric carbons in the tartaric acid molecule, tartaric acid has three stereoisomers, D-form, L-form and meso-form, and D-form and L-form tartaric acid have optical activity. Have.

  Therefore, the specific rotation of the crystal obtained above was measured to determine its optical purity. That is, 20 mg of the crystal was dissolved in 2 ml of pure water, and the optical rotation was measured three times with a polarimeter (high-speed automatic polarimeter SEPA-300, manufactured by Horiba) equipped with a microcell. Asked. Further, the melting point of the crystal was measured three times with a melting point measuring instrument (model MP-500D, manufactured by Yanagimoto Seisakusho Co., Ltd.). The results are shown in Table 12.

  As shown in Table 12, the specific rotation and melting point of the crystal are approximate values for the reported specific rotation and melting point of D-tartaric acid, and are consistent with the retention time in the above-mentioned HPLC. The crystals were identified as D-tartaric acid.

Claims (9)

A method for producing D-tartaric acid or a salt thereof from potassium 4-keto-D-arabonate,
A carbonate is aerobically contacted with an aqueous solution containing potassium 4-keto-D-arabonate to produce D-tartaric acid or a salt thereof in the reaction solution,
A method for producing D-tartaric acid or a salt thereof. The carbonate is potassium carbonate ;
The method for producing D-tartaric acid or a salt thereof according to claim 1. The concentration of the potassium carbonate salt is 0.005 to 1.5M.
The manufacturing method of D-tartaric acid or its salt of Claim 1 or 2. The potassium carbonate salt ;
Contacting with at least one transition metal compound selected from the group consisting of a copper compound, a manganese compound, a nickel compound, and an iron compound;
The manufacturing method of D-tartaric acid or its salt of any one of Claims 1-3. The transition metal compound is composed of copper oxide (II), basic copper carbonate (II), manganese sulfate (II), manganese oxide (IV), nickel sulfate (II), iron sulfate (II), iron sulfate (III). At least one transition metal compound selected from the group consisting of:
The manufacturing method of D-tartaric acid or its salts of Claim 4. The concentration of the transition metal compound is 0.0001 to 2% (w / v).
The manufacturing method of D-tartaric acid or its salt of Claim 4 or 5. The reaction is performed at pH 8-12, temperature 15-60 ° C. for 1-5 days,
The manufacturing method of D-tartaric acid or its salt of any one of Claims 1-6. And further, a step of purifying D-tartaric acid or a salt thereof from the reaction solution.
The manufacturing method of D-tartaric acid or its salt of any one of Claims 1-7. The D-tartrate purified in the purification step is a monopotassium salt of D-tartaric acid.
A method for producing D-tartaric acid or a salt thereof according to claim 8.