JPS63132856A - Production of pyruvate - Google Patents

Abstract

PURPOSE:To obtain the titled compound which is a synthetic raw material for amino acids in one process in a simple apparatus without using an acid catalyst causing troublesome reaction, by hydrolyzing and neutralizing a pyruvic acid ester in the presence of water and a base catalyst. CONSTITUTION:A pyruvic acid ester is hydrolyzed and neutralized in the presence of water and a base catalyst at 0-60 deg.C, particularly 10-50 deg.C, preferably in an inert gas atmosphere, e.g. nitrogen, etc., to afford the aimed compound. An inorganic compound of an alkali metal or alkaline earth metal such as LiOH, NaOH, CaO, Pb2CO3, etc., is used in the form of a solution dissolved in water or suspension, etc., as the base catalyst in <=50wt% concentration by dripping into the reaction system. The molar amount of the water used for the reaction is 10-200 times, preferably 30-100 times based on the raw material pyruvic acid ester. The pH of the reaction system is <=12, preferably about 10-6.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing pyruvic acid salts by hydrolyzing and neutralizing pyruvic acid esters.

Pyruvate is a compound useful as a raw material for synthesizing amino acids such as citribut7in by enzymatic reactions.

[Conventional technology]

An industrially advantageous method for producing pyruvate is a method in which pyruvate is hydrolyzed to produce pyruvic acid, which is then neutralized with an aqueous solution of an alkali metal mineralized adduct.

However, pyruvic acid esters, pyruvic acid, and pyruvate salts are highly reactive compounds, and side reactions such as condensation are likely to proceed particularly under basic conditions. Therefore, methods using acid catalysts have been proposed for the hydrolysis of pyruvate esters. For example, (1) the method (% opening 56-4
0638), (2) 50 in the presence of water and an acid catalyst
At a temperature of ~80°C and a conversion of pyruvate ester of 9
8 or less and unreacted substances are distilled off as an azeotrope with water (Japanese Unexamined Patent Publication No. 61-27941). Then, the obtained pyruvic acid is treated with activated carbon having an iron content of so ppm or less, and is neutralized at a temperature of 30 tons or less and while maintaining the reaction system's put-6 or less (Japanese Patent Application Laid-Open No. According to Japanese Patent No. 61-27940), it has been proposed to produce pyruvate by two steps of hydrolysis and neutralization using different reaction conditions from pyruvate ester. but,
The hydrolysis reaction using an acid catalyst is a reversible reaction, and the alcohol produced must be distilled out of the system. In order to distill off this alcohol, the inside of the reaction system must be maintained at a constant reduced pressure. In addition, in order to prevent the raw materials from distilling off, it is necessary to keep the temperature at the top of the tower constant.If some of the raw materials remain in the middle of the tower as an azeotropic mixture with water, the hydrolysis rate will decrease, so the temperature at the top of the tower must be kept constant. Although this is a complicated method, such as the need to circulate part of the reaction mixture to the middle stage, it is conceivable that a part of the raw material will still be distilled out.

[Problem that the invention seeks to solve]

As mentioned above, acid-catalyzed hydrolysis is preferable for the stability of raw materials and products, but the reaction becomes very complicated. The present invention provides a method for producing pyruvate from pyruvate ester in one step in order to solve these drawbacks.

[Means for solving problems]

The present invention is a method for producing pyruvate in a -step by subjecting pyruvate ester to hydrolysis and neutralization reaction in the presence of water and a basic catalyst.

According to the BAK of the present invention, it is possible to produce pyruvate by hydrolysis reaction and neutralization reaction of pyruvate ester in one step and using a very simple reaction apparatus.

In the reaction method of the present invention, pyruvate ester is dissolved in water, stirred, and when a predetermined temperature is reached, an aqueous solution of a base catalyst is formed into a suspension I! Alternatively, the powder is added dropwise while measuring the pH of the reaction solution. The produced alcohol is recovered by a method such as depressurization after the reaction is completed.

Examples of the pyruvate ester used as a starting material in the present invention include methyl pyruvate, ethyl pyruvate, n-propyl pyruvate, and n-butyl pyruvate.

In the present invention, base catalysts include inorganic compounds of alkali metals and alkaline earth metals, such as LiOH, NaO
H, KOH% RbOH, Cs0HXCa(OH)x,
Hydroxide such as 5r(OH)z, Ba(OH), etc.: Na
Oxides such as 2O, K, 01CslO, CaO1SrO1BaO: NazCOi, KtCOs, RbzCOi
, C5zCO, carbonates such as % NaHCOl, and ammonia. The above-mentioned catalysts are dissolved in water, suspended in water, or in the form of powder, and used dropwise into the reaction system.

The amount of water for dissolving the pyruvate ester in the reaction system is suitably 10 to 200 times the amount of the pyruvate ester, particularly preferably 30 to 100 times the amount of water. If the amount of water used is too small, the reaction will be slow and the amount of by-products such as condensate will increase. Moreover, if the amount of water is too large, the concentration of pyruvate produced will be low and the process will not be efficient.

The pH of the reaction system is preferably 12 or less, preferably 10 or less. When pyruvate ester is dissolved in water and stirred, hydrolysis occurs and the pH decreases. When a base catalyst is dropped there, the pH rises as the catalyst is dropped until it reaches around pH 6, but from around 6, when an aqueous medium is dropped, the pH instantly rises to 8-9 and then quickly It also drops to around 6. This dropping operation is carried out within a pH range of about 10 to 6. When the pH is strongly basic for a long time @-
However, since the amount of by-product of the condensation product increases, it is preferable to maintain the pH at about 6-7 even if it is within the range of 10-6.

The amount of base catalyst used in the process of the invention is less than or equal to the amount of pyruvate ester. If the amount of catalyst is present in excess of an equivalent amount, the pH of the reaction system will be 13 or higher, and the amount of by-products such as condensation products will increase.

When the base catalyst to be added dropwise is in the form of powder, solution or suspension, an aqueous solution or suspension with a concentration of 50% by weight or less is preferable, since if the concentration is too high, the amount of by-products such as condensates will increase.

The reaction temperature is suitably 0°C to 60°C, especially 10 to 50°C.
°C is preferred. If the reaction temperature is too low, the reaction rate is too slow to be practical, and if the reaction temperature is higher than 60°C, the amount of by-products such as condensates increases.

The reaction time is not particularly limited as it is related to the reaction temperature, etc., but since the reactivity of the product is high, it is preferably as short as possible, preferably 10 hours or less, and more preferably 5 hours or less. It is better to complete the reaction within a certain amount of time.

Since the present invention uses a base catalyst, there is no need to carry out the reaction while distilling off the alcohol produced from the reaction system. Therefore, the reaction system can be at normal pressure, and there is no need to reduce the pressure. There is no concern at all about the distillation of raw materials used in water. The optimum reaction temperature can be selected regardless of the boiling point of the alcohol produced.

Note that the alcohol produced is preferably recovered under reduced pressure after the reaction is completed.

The atmosphere of the reaction system may be air, but it is more preferably an atmosphere of an inert gas such as nitrogen, argon, or helium.

Since pyruvic acid is considered to exhibit strong acidity during the reaction, metal ions may be eluted from the reactor depending on the material of the reactor. The eluted metal ions may promote side reactions and inhibit the reaction when the next enzymatic reaction is performed. Therefore, the materials for the reactor are glass, JIS standard, SUS 304, and SUS.
Stainless steel such as 316 is preferred.

Since the pyruvate obtained by the reaction is an aqueous solution, if you want to further condense the pyruvate or isolate the pyruvate, #i. It can be concentrated to a concentration of K.

Examples of pyruvates obtainable by the method of the invention include lithium pyruvate, sodium pyruvate, potassium pyruvate, rubidium pyruvate, cesium pyruvate, calcium pyruvate, strontium pyruvate, barium pyruvate, ammonium pyruvate. Examples include. These pyruvate salts can be manufactured as appropriate depending on the purpose.

Note that the pyruvate ester as a raw material can be easily obtained by a known method such as subjecting the corresponding lactic acid ester to an oxidative dehydrogenation reaction.

EXPERIMENTAL EXAMPLES Next, the present invention will be explained in more detail with reference to Examples and Comparative Examples.

Incidentally, pyruvate was analyzed by high performance liquid chromatography and quantified as pyruvic acid. It was clear from the isolate of Example 1 and the pH of each reaction solution that it was a pyruvate, and the yield was reported as pyruvate.

Example 1 Methyl pyruvate (Gyudon Chemical Co., Ltd.) 2.55 f (25 mmol) was placed in a 100 m four-hole flask equipped with a thermometer, a dropping tube), a pH meter electrode, and a magnetic stirrer.
and 40 f (2.22 mol) of water were added and stirred using a magnetic stirrer. The reaction solution had a pH of 1.99 and was a homogeneous colorless solution. Sodium hydroxide (manufactured by Wako Tsumugi Pharmaceutical Co., Ltd.) was added to the reaction solution.1. Of (25 mmol)
was dissolved in 11.5 f of water. Concentration 8% by weight 1
An aqueous sodium hydroxide solution was added dropwise over 15 minutes while maintaining the reaction temperature at 20-25°C. The patient developed a slight fever and was sad. The pH during this period was between 6 and 1O, and the dropwise addition was completed when the pH was within the range of 6 to 8. The pH was 7.01 at the end of dropping an equivalent amount of sodium hydroxide, and the pH continued to drop slightly thereafter. 1 hour after completion of dropping, reaction temperature 2
Stirring was carried out while maintaining the temperature at 0 to 30°C. Analysis of the reaction solution by high performance liquid chromatography revealed that the yield of pyruvic acid was 96.8%, and the reaction solution was almost colorless. Water and methanol were distilled off from the reaction solution under reduced pressure, and the solution was concentrated until pyruvate was precipitated. The liquid volume at this time was 7°8f, and this concentrated liquid was filled with isopropanol 30
2 was added to precipitate white crystals. The crystals were filtered, washed and dried to obtain 2.58f white crystals.

The isolated yield was 93.7, and the product was confirmed by NMR.

Example 2 Using the same reactor as in Example 1, the reaction temperature was t-40 to 45.
The raw materials and water were charged in the same manner, except that the temperature was changed to ℃. It was heated in a hot water bath, and when the temperature of the reaction solution reached 40° C., the pH was 1.92.

The dropping of the sodium hydroxide aqueous solution Fi was completed in 5 minutes.

The pH therebetween was in the range of 6-9. After finishing the dripping, 2
The mixture was stirred for an hour while maintaining the reaction temperature at 40-45°C.

As a result of analyzing the reaction solution by high performance liquid chromatography, the yield of sodium pyruvate was found to be Fi96.1 after 1 hour.
6%, and 98.2% after 2 hours. The reaction solution was almost colorless.

Example 3 Using the same reaction apparatus as in Example 1, the reaction conditions were the same as in Example 2, except that the concentration of the aqueous sodium hydroxide solution added dropwise was changed by 50% by weight.

pH before dropping): tl, 87, dropping pH 6-9
It was carried out within the range of The dripping was completed in 2 minutes and then for 2 hours.
The mixture was stirred while maintaining the temperature. Analysis of the reaction solution by high performance liquid chromatography revealed that the yield of sodium pyruvate was 94.4%.

The reaction solution was almost colorless.

Example 4 In a reactor similar to Example 1, methyl pyruvate 5.1
? The reaction conditions were the same as in Example 1, except that 37.49 (50 mmol) and 37.49 (2.08 mol) of water were charged. hydroxide) pHFil before dropping IJum aqueous solution,
84, and the dropping was performed in the pH range of 6 to 10. The dropwise addition was completed in 2 minutes, and the mixture was stirred for 2 hours while maintaining the temperature. As a result of analyzing the reaction solution by high performance liquid chromatography, the yield of sodium pyruvate was 98.2.
%Met. The reaction solution was almost colorless.

Example 5 The reaction was carried out using the same reaction apparatus as in Example 1 and under the same reaction conditions as in Example 2, except that 2.9 f (25 mmol) of ethyl pyruvate (manufactured by Tokyo Kasei) was used. The pH before dropping the sodium hydroxide aqueous solution was 2.34, and the pH before dropping was 6.
-9. The dropwise addition was completed in 15 minutes, and the mixture was stirred for 2 hours while maintaining the temperature. As a result of analyzing the reaction solution by high performance liquid chromatography, the yield of sodium pyruvate was 94.1. The reaction solution was almost colorless.

Example 6 In the same reactor as in Example 1, the base catalyst was added dropwise to a concentration of 25% by weight aqueous ammonia of 1.70% by weight. (25 mmol) The reaction was carried out under the same conditions as in Example 1 except that K was changed. The pE before dropping ammonia water was 2.OO, and the dropping FipH was in the range of 6 to 9. The dropping was completed in 35 minutes, and then stirred for 2 hours while maintaining the temperature. As a result of the two-fee analysis,
The yield of ammonium pyruvate was 92.5%.

The reaction solution was almost colorless.

Example 7 In a reactor similar to Example 1, a base catalyst was added dropwise to a 15% by weight aqueous sodium carbonate solution at a concentration of 8.8% by weight.
The reaction conditions were the same as in Example 1 except that the amount was changed to (12.5 mmol). The pH before dropping IJium carbonate was 1.90, and the dropping was carried out within the range of hpas to 9. The dropwise addition was completed in 5 minutes, and the mixture was stirred for 2 hours while maintaining the temperature. As a result of analyzing the reaction solution by high performance liquid chromatography, the yield of sodium pyruvate was 89.6.
%Met.

The reaction solution took on a slightly yellow color.

Example 8 In the same reactor as in Example 1, a basic catalyst was added dropwise to a concentration of 5% by weight barium hydroxide aqueous fi42.9.
F (12.5 mmol) Example 1 except that I/c was changed.
The reaction was carried out under the same reaction conditions. p before dropping barium hydroxide
Htil, 93 was used, and the dropping was carried out in the range of I) H6-9. The dropwise addition was completed in 20 minutes, and the mixture was stirred for 2 hours while maintaining the temperature. The reaction solution was analyzed by high performance liquid chromatography, and the barium pyruvate content was 84.7%. The reaction solution took on a slightly yellow color.

COMPARATIVE EXAMPLE Hydroxylation was carried out in the same reactor as in Example 1) IJum2.
8 f (70 mmol) and 32.29 g of water were charged. (Sodium hydroxide concentration Fi 8% by weight at this time), 5.259 (50 mmol) of methyl pyruvate was added to the dropping funnel at a reaction temperature of 20 to 30°C.
It was dripped in minutes. The pH before dropping was 14.10 and 13.81 after finishing dropping.

After stirring for 30 minutes, the reaction solution was analyzed by high performance liquid chromatography, and the yield of sodium pyruvate was 118.6%. Several other liquid chromatography peaks were observed, and the reaction solution also had a deep yellow color.

Claims (1)

[Claims] A method for producing pyruvate by hydrolyzing and neutralizing pyruvate ester in the presence of water and a base catalyst