JPH07238063A - Method for recovering and purifying 5-aminolevulinic acid - Google Patents

Abstract

PURPOSE:To obtain white and high-purity 5-aminolevulinic acid in high yield according to simple operations without carrying out troublesome recrystallizing operations such as those in a conventional method. CONSTITUTION:This method for recovering and purifying 5-aminolevulinic acid is to cool a solution, containing 5-aminolevulinic acid and obtained by hydrolyzing 5-phthalimidolevulinic acid with hydrochloric acid to <=10 deg.C, deposit phthalic acid as a crystal, then carry out the decoloring treatment with active carbon, concentrate the resultant solution to dryness and wash the obtained crystal with ethanol.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for recovering and purifying 5-aminolevulinic acid from a reaction solution containing 5-aminolevulinic acid synthesized by a chemical method.

[0002]

BACKGROUND OF THE INVENTION 5-Aminolevulinic acid is a biosynthetic intermediate such as heme and vitamin B ₁₂ , and is a compound useful as a raw material for agricultural chemicals and chemicals, and as a herbicide.

Conventionally, as a method for producing 5-aminolevulinic acid, (1) a method of introducing a phthalimide group at the 5-position of levulinic acid and then hydrolyzing the phthalimide group, (2) an amino group of tetrahydrofurfurylamine Is protected as phthalimide, followed by oxidation and ring opening, and finally hydrolysis of the phthalimide group. (3) After protecting the amino group of furfurylamine as phthalimide, oxidation, ring opening, and reduction are performed, and finally It is known to hydrolyze the phthalimide group, (4) cyanate a monoester of succinic acid, reduce it, and then hydrolyze it. In many of these methods, phthalimide is used to protect the amino group. ing.

Therefore, according to these methods, the phthalimido group must be hydrolyzed to remove the phthaloyl group in the final step. To remove the phthaloyl group, a method of hydrolyzing the phthalimido group with hydrochloric acid is performed. The 5-aminolevulinic acid produced there is mainly dissolved in a hydrochloric acid solution as a mixture with phthalic acid. Therefore, usually, the phthalic acid that is left to stand at room temperature is filtered off, then concentrated to dryness under reduced pressure, and the resulting crystals are recrystallized using a water-ethanol mixed solvent to give 5-aminolevulinic acid. A method of collecting and purifying is used.

However, the above-mentioned hydrolysis with hydrochloric acid is liable to cause coloration due to severe reaction conditions, and in order to obtain white highly pure 5-aminolevulinic acid, recrystallization is repeated many times. Although it has to be carried out using a large amount of solvent, this has a drawback that it requires a lot of labor and leads to a decrease in recovery rate. Also,
As this decolorization method, a method of treating the reaction solution with activated carbon can be considered, but this method has a problem that almost no decolorization effect can be obtained.

[0006]

SUMMARY OF THE INVENTION Therefore, the present invention provides 5
-Produced by hydrolyzing phthalimidolevulinic acid 5-
It is intended to provide a method for recovering white, highly pure 5-aminolevulinic acid in high yield from a solution containing aminolevulinic acid by a simple operation.

[0007]

Under such circumstances, the present inventor has conducted earnest research on the decolorization method of the above-mentioned reaction solution containing aminolevulinic acid. As a result, almost no decolorizing effect can be obtained by treating this reaction solution or the solution obtained by precipitating phthalic acid at room temperature with active carbon, which is generally used. This is because the phthalic acid dissolved in is adsorbed on the activated carbon and inhibits its decolorization effect.Therefore, if the reaction solution is cooled to precipitate the dissolved phthalic acid as completely as possible, it is necessary to treat it with activated carbon. The present invention has been completed by finding that decolorization is effectively performed.

That is, according to the present invention, in recovering and purifying 5-aminolevulinic acid from a solution containing 5-aminolevulinic acid obtained by hydrolyzing 5-phthalimidolevulinic acid with hydrochloric acid, the solution containing 5-aminolevulinic acid is heated to 10 ° C. The present invention provides a method for recovering and purifying 5-aminolevulinic acid, which comprises cooling and precipitating phthalic acid as crystals, followed by decolorizing treatment with activated carbon.

As the 5-phthalimidolevulinic acid in the method of the present invention, any of those prepared by the above-mentioned known method can be used. Hydrolysis of 5-phthalimidolevulinic acid with hydrochloric acid is carried out by a known method. If the concentration of the hydrochloric acid solution at this time is less than 1N, the reaction takes a long time, and if it exceeds 10N, hydrochloric acid is generated during heating under reflux. Since it may be released as a gas, it is generally 1 to 10 N, preferably 4 to 10 N.

The hydrolysis reaction solution is cooled to 10 ° C. or lower to completely precipitate phthalic acid dissolved in the solution in a supersaturated state. The cooling temperature may be 10 ° C. or lower, but excessive cooling increases the cost, so 0 is practically used.
5 ° C is preferred. The cooling time varies depending on the concentration of 5-aminolevulinic acid in the reaction solution, the cooling temperature, etc., but the concentration of 5-aminolevulinic acid which is a normal reaction condition is 1 to 20.
In the range of weight% (hereinafter, simply referred to as%), when the cooling temperature is 5 ° C, 2 hours or more, particularly 3 hours or more are effective.

By doing so, the phthalic acid dissolved in the reaction solution is almost completely precipitated as crystals. The precipitated crystals of phthalic acid can be removed by filtration, etc., but this does not necessarily have to be removed at this time, and activated carbon is added to the solution containing the phthalic acid crystals to carry out a decolorization treatment to remove the activated carbon. At the same time, the phthalic acid crystals can be removed.

The decolorization treatment with activated carbon needs to be carried out by adding activated carbon to the reaction solution after the phthalic acid crystals have been precipitated, and even if it is added to the reaction solution before the precipitation of phthalic acid crystals, the decolorization effect is almost eliminated. I can't get it. The amount of activated carbon used is 5 dissolved
-If the amount of aminolevulinic acid (conversion rate from 5-phthalimidolevulinic acid is 100%) is 1% or more, the effect can be obtained. However, if the amount used is small, the treatment takes a long time. 10% or more is particularly preferable. The treatment temperature is not particularly limited and is usually room temperature.

The decolorizing treatment with activated carbon may be carried out in a batch system or in a flow system using a column packed with activated carbon. In the case of the flow type, it is necessary to remove the precipitated phthalic acid crystals and then flow into the column. After decolorizing with activated carbon, the activated carbon is removed by filtration or the like. At this time, if precipitated crystals of phthalic acid are present, they are also removed together with the activated carbon.

Crystals of 5-aminolevulinic acid (hydrochloride) are obtained by distilling off the solvent and residual hydrochloric acid from the solution containing 5-aminolevulinic acid decolorized in this way. The solvent and residual hydrochloric acid are preferably distilled off at a low temperature under reduced pressure so that decomposition of 5-aminolevulinic acid does not occur. It is usually preferably carried out at a temperature of 70 ° C. or lower, particularly 50 ° C. or lower.

The crystals of 5-aminolevulinic acid thus obtained can be converted into white needle crystals simply by washing with ethanol without subjecting them to recrystallization from a conventional water-ethanol mixed solvent. You can

This ethanol washing is performed to remove impurities adhering to the surface of the 5-aminolevulinic acid crystal. If the amount of ethanol used is too small, the dissolution and removal of impurities will be inadequate, and if too large, 5-
Since the yield is lowered due to dissolution of aminolevulinic acid, the minimum amount is preferable so that a uniform slurry state can be obtained by stirring. Generally, it is preferable to use 5 to 20 ml per 10 g of 5-aminolevulinic acid crystals. The temperature of the cleaning alcohol is preferably 0 to 25 ° C, particularly preferably 0 to 10 ° C.

The ethanol washing can be carried out by adding ethanol to the 5-aminolevulinic acid crystals and stirring the mixture to form a slurry, and then separating the 5-aminolevulinic acid crystals by filtration, centrifugation or the like.

Since ethanol is attached to the surface of the thus-obtained 5-aminolevulinic acid crystal, it is preferable that the crystal is secondarily washed with a small amount of ethanol. The amount of ethanol used in the secondary washing is preferably about half that in the case of the primary washing. The temperature of ethanol for secondary washing is preferably 25 ° C or lower, and particularly preferably 10 ° C or lower.

[0019]

According to the method of the present invention, white highly pure 5-aminolevulinic acid can be obtained in a high yield by a simple operation without performing a troublesome recrystallization operation as in the prior art.

[0020]

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited thereto.

Example 1 20.0 g (76.6 mmol) of 5-phthalimidolevulinic acid and 800 ml of 6N-hydrochloric acid were placed in a 1-liter glass flask equipped with a reflux condenser and heated under reflux for 10 hours. The flask containing the reaction solution was cooled to room temperature with water, and then allowed to stand in a refrigerator at 5 ° C. for 3 hours to precipitate phthalic acid crystals. Next, 5 g of activated carbon was added thereto, and the mixture was stirred at room temperature for 3 hours, and then the solid content (activated carbon and phthalic acid crystals) was removed by filtration. Hydrochloric acid and water were distilled off from this solution under reduced pressure to obtain 12.6 g of pale yellow crystals. To the pale yellow crystals, 10 ml of ethanol at 5 ° C. was added and stirred, and the crystals obtained by filtration were further washed with 5 ml of ethanol at 5 ° C. on the filter paper to replace the primary washing liquid, and then dried under reduced pressure to 5 −
9.39 g (yield 73%) of white needle crystals of aminolevulinic acid hydrochloride were obtained. The melting point of this product is 150-151 ° C.
It was (decomposition).

Comparative Example 1 The same operation as in Example 1 was carried out except that the activated carbon treatment was carried out on the reaction solution before the precipitation of phthalic acid crystals by cooling. As a result, the crystals of 5-aminolevulinic acid hydrochloride before washing with ethanol were dark brown, and the crystals obtained by washing this with ethanol were brown crystals with a melting point of 147 to 150 ° C. (decomposition). The yield was 9.46 g (yield 74
%)Met.

Comparative Example 2 In a 1 liter glass flask equipped with a reflux condenser, 20.0 g (76.6 mmol) of 5-phthalimidolevulinic acid was added.
Then, 800 ml of 6N hydrochloric acid was added and the mixture was heated under reflux for 10 hours. The flask containing the reaction solution was allowed to stand at room temperature for 3 hours, and the precipitated phthalic acid crystals were removed by filtration. Next, 5 g of activated carbon was added thereto, and the mixture was stirred at room temperature for 3 hours, and then the solid content was removed by filtration. Hydrochloric acid and water were distilled off from this solution under reduced pressure to obtain 12.8 g of dark brown crystals. The crystals were washed with ethanol in the same manner as in Example 1 to obtain 9.48 g (74%) of brown 5-aminolevulinic acid hydrochloride crystals.
%) Was obtained. The melting point of this product was 146 to 150 ° C. (decomposition).

Comparative Example 3 20.0 g (76.6 mmol) of 5-phthalimidolevulinic acid was placed in a 1 liter glass flask equipped with a reflux condenser.
Then, 800 ml of 6N hydrochloric acid was added and the mixture was heated under reflux for 10 hours. The flask containing the reaction solution was allowed to stand at room temperature for 3 hours, and the precipitated phthalic acid crystals were removed by filtration. The filtrate was concentrated to dryness under reduced pressure to obtain 12.9 g of brown crystals. Then, the crystals were dissolved by heating in 10 ml of water-ethanol (2: 8) and allowed to cool to recrystallize. The precipitated crystals were filtered, and the crystals were washed on a filter paper with 5 ml of ethanol at 5 ° C. to replace the mother liquor, and the obtained crystals were dried under reduced pressure to give 5
-7.86 g (61% yield) of white crystals of aminolevulinic acid hydrochloride were obtained. The melting point of this product was 150 to 151 ° C.

Claims (2)

[Claims] 1. When recovering and purifying 5-aminolevulinic acid from a solution containing 5-aminolevulinic acid obtained by hydrolyzing 5-phthalimidolevulinic acid with hydrochloric acid, the solution containing 5-aminolevulinic acid is cooled to 10 ° C. or lower. The method for recovering and purifying 5-aminolevulinic acid is characterized in that phthalic acid is precipitated as crystals and then decolorized with activated carbon. 2. A method of precipitating and removing phthalic acid crystals according to claim 1 and decolorizing the resulting solution, the solution containing 5-aminolevulinic acid is concentrated to dryness, and the resulting crystals are washed with ethanol. A method for collecting and purifying 5-aminolevulinic acid.