JPS62142143A - Purification and separation of dl-phenylalanine - Google Patents

Abstract

PURPOSE:To deposit and separate DL-phenylalanine in high quality, by reacting 2-chloro-3-phenylpropionic acid with aqueous ammonia and adding a lower aliphatic alcohol to the resultant reaction solution of the DL-phenylalanine. CONSTITUTION:2-Chloro-3-phenylpropionic acid is reacted with aqueous ammonia to give a reaction solution of DL-phenylalanine and a lower aliphatic alcohol, e.g. methanol, is then added thereto to crystallize the DL-phenylalanine, which is purified and separated. If the ammonia is recovered from the reaction solution of the DL-phenylalanine by distillation and the DL-phenylalanine is deposited and separated by an ordinary method for concentrating and cooling the residual solution, etc., there are problems of bad coloring and solution state of hydrochloric acid (presence or absence of a colored state or suspended materials of a phenylalanine solution in hydrochloric acid). The aimed DL-phenylalanine of high quality, particularly improved hue, however, can be obtained by this method.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a novel purification and separation method for DL-phenylalanine.

More specifically, DL-phenylalanine of high quality, particularly excellent color, is purified and separated in one step from a reaction solution containing DL-phenylalanine obtained by reacting 2-chloro-8-phenylpropionic acid with aqueous ammonia. Regarding the method.

Phenylalanine is an essential amino acid and is also useful as an intermediate for analgesics and sweeteners.

<Prior art> DL-phenylalanine has been disclosed in R. Kokai No. 60-81157 and Can, J. Research, 2388 (
1945), 2-chloro-3-phenylpropionic acid and aqueous ammonia were heated at 50°C.
It is obtained by reacting at a reaction temperature of -150'C.

JP-A No. 60-81157 discloses that ammonia is recovered from a DL-phenylalanine reaction solution by distillation, and the remaining liquid is concentrated, cooled, or isoelectrically focused to obtain DL-
It is described that phenylalanine crystals can be precipitated and isolated.

To purify isolated phenylalanine crystals, the crystals are generally washed with water or alcohol, or recrystallized.

JP-A-60-161952 discloses that N-acetyl-
A purification method using activated carbon is described for hydrolyzing D,L-phenylalanine with aminoacylase to obtain L-phenylalanine with high selectivity.

Furthermore, JP-A-60-161952 also describes that purification using an ion exchange resin is also possible.

<Problems to be Solved by the Invention> When ammonia is recovered from the reaction solution of DL-phenylalanine by distillation, and crystals of DL-phenylalanine are precipitated and separated by conventional methods such as concentrating and cooling the residual solution,
There is a problem in that DL-phenylalanine has poor coloration and poor hydrochloric acid solubility (the colored state of the hydrochloric acid solution of phenylalanine and the presence or absence of suspended substances). There is also the problem that the soil and by-product ammonia nitrogen such as ammonium cinnamate and ammonium chloride are contained in the wastewater.

As a method to solve the problem of hue, even if the colored crystals are washed again with water or alcohol, no improvement in coloring or hydrochloric acid solubility is observed. Furthermore, in the method of recrystallizing after separating the crude crystals, the loss to the solvent is large and the separation yield is considerably reduced, and only a slight improvement in quality is observed. The method of treatment with activated carbon requires a large amount of activated carbon, and a large amount of phenylalanine is adsorbed to the activated carbon and lost. Purification using an ion exchange resin requires dilution and dissolution in order to pass through the solution at a low concentration, and it is said that the concentration load is too large.

As described above, the conventional technique is difficult to solve the problems of coloration and hydrochloric acid dissolution without impairing the separation yield, and requires many processing steps, and is not an industrially preferable method.

Means for Solving the Problems> The present inventor has intensively studied an industrially advantageous purification and separation method for DL-phenylalanine, and has developed a method for reacting 2-chloro-8-phenylpropionic acid with aqueous ammonia. By adding a lower aliphatic alcohol to the reaction solution of DL-phenylalanine obtained at least to crystallize DL-phenylalanine, it is possible to purify DL-phenylalanine with high quality, especially excellent color, without impairing the separation yield. He discovered a separation method and completed the present invention.

Since the reaction between 2-chloro-8-phenylpropionic acid and aqueous ammonia is usually carried out in excess of ammonia, excess ammonia remains in the reaction solution, so ammonia is recovered by distillation.

When 2-chloro-3-phenylpropionic acid and aqueous ammonia are reacted, in addition to DL-phenylalanine, ammonia is recovered from ammonium cinnamate, ammonium chloride, etc., and alkali is added to reduce ammonia nitrogen in wastewater. Preferably, ammonia is recovered by adding metal hydroxide.

Examples of the alkali metal hydroxide used in the present invention include sodium hydroxide, potassium hydroxide, and lithium hydroxide.

The amount of alkali metal hydroxide used per liter is preferably 0.8 to 1.05 times the mole of 2-chloro-8-phenylpropionic acid.

If the alkali metal hydroxide used 11 is less than this range, the daily yield of ammonia will decrease. On the other hand, if it is larger than this range, the separation yield of DL-phenylalanine decreases, which is not preferable.

In the present invention, a lower aliphatic alcohol is added to the reaction solution of DL-phenylalanine obtained by reacting 2-chloro-3-phenylpropionic acid and aqueous ammonia, and the mixture is refluxed at °C. When adding alcohol, it is better to do it before or after recovering ammonia. If ammonia is recovered after adding alcohol, alcohol will be included in the recovered ammonia, so if it is used directly in the reaction, the pressure during the reaction will increase, After ammonia is recovered by adding an alkali metal oxide to the reaction solution, it is preferable to add a lower aliphatic alcohol and perform a reflux treatment.

The lower aliphatic alcohol used in the present invention only needs to be compatible with water, such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, i-butanol, or t-butanol. Butanol etc.

Among these lower aliphatic alcohols, methanol, ethanol or i-propanol is preferred.

The alcohol concentration is 25 VO 1% or more, particularly preferably 80 to 7 Q VO 1%.

If the amount of alcohol used is less than this range, DL-
Phenylalanine coloring and hydrochloric acid layering are poor. On the other hand, if it is larger than this range, there will be no problem in refining, but it will be unfavorable because it will be uneconomical.

In the present invention, the DL-phenylalanine reaction solution obtained by reacting 2-chloro-8-phenylpropionic acid with aqueous ammonia is treated by adding alcohol, and the treatment temperature is 40 to 120"C1, preferably 50"C. ``C'' is the boiling point of the alcohol aqueous solution.

You can just add alcohol and mix, but 1-2
The solubility in hydrochloric acid is improved by returning for a longer period of time.

If the treatment temperature is lower than this range, the coloring and salt solubility of DL-phenylalanine will deteriorate. Conversely, if it is larger than this range, no commensurate effect can be obtained.

Regarding the processing pressure of the present invention, there will be no problem as long as it is within the wA range that can maintain the boiling point of the alcohol aqueous solution at a level that does not exceed the above processing temperature.

Most of the D L--phenylalanine condensate +M+ is refluxed with alcohol and then cooled to be filtered out, which is then collected from house to house.

<Example> The present invention will be explained in more detail with reference to Examples below.

In addition, in the following examples, 5 g of phenylalanine was dissolved in 2N salt fi100- as a hydrochloric acid layer, and 10 m
By measuring the transmission percentage of 48Q nm using a cell and using a spectrophotometer with 4 shadows, the coloring state of phenylalanine and the degree of absence of insoluble matter can be expressed quantitatively.

Example 1 2-chloro-3-phenylpropionic acid 55.49 (
0.8 mol) and 25% by weight ammonia water 408F (6 mol) were placed in a 10100O glass autoclave.
It was heated to 85"C and reacted for 6 hours. The reaction yield of υL-phenylalanine was 89 mol% based on 2-chloro-8-phenylpropionic acid. After that, 40%
After adding 80 y of sodium hydroxide solution and recovering excess ammonia by distillation, 800 rnt of methanol was supplied and refluxed. After this, the cooled and precipitated product was distributed door to door,
The cleaning rate was increased with cold methanol. Thus, crystals of DL-phenylalanine 84.8
I got 1. The separation yield was 86.7% based on the product L-phenylalanine. The purity of the obtained crystals was 99
．． 8%, 5 g of this crystal was dissolved in 100-2N hydrochloric acid, and measured with a spectrophotometer using a 101 cell at 80 nm.
The transmission percentage was measured and was 95%.

Example 2 Methanol 150 instead of methanol 800rrLt
The same procedure as in Example 1 was conducted except that WLt was used. DL-
84.4 f of crystals of phenylalanine were obtained. The separation yield was 86.0% based on the product L-phenylalanine.

The purity of the obtained crystals was 991%.

Percent transmission was 80%.

Example 8 The same procedure as in Example 1 was carried out except that 90 methanol was used instead of 800 methanol. 84.4y of crystals of DL-phenylalanine were obtained. The separation yield was 85.8% based on the product L-phenylalanine.

The purity of the obtained crystals was 99.0%.

Percent transmission was 70%.

Example 4 The same procedure as in Example 1 was carried out except that 60 rnt of methanol was used instead of 300 ml of methanol. 84.8 f of crystals of DL-phenylalanine were obtained. The separation yield was 86.8% based on the product L-phenylalanine.

The purity of the obtained crystals was 98.5%.

Percent transmission was 60%.

Comparative Example 1 The same procedure as in Example 1 was carried out except that 40% sodium hydroxide solution 861 was used instead of 30 g of 40% sodium hydroxide solution.

It was 70.0% based on DL-phenylalanine.

The purity of the obtained crystals was 99.0%. Percent transmission was 93%.

Comparative Example 2 The same procedure as in Example was carried out except that MEC/-L was not used in place of 800 nL of methanol. 84.8 g of DL-phenylalanine crystals were obtained. The separation yield was 85.2<s based on the product L-phenylalanine.

The purity of the obtained crystals was 97.0! It was Q5.

The transmission percentage is 50%.

Comparative example 3 Obtained in the same manner as Comparative Example 2. Supply 800% of tanol and return 5! Let's do it too.

After cooling, crystals of DL-phenylalanine 84.2
I got f. The separation yield was 85.0% based on the produced L-phenylalanine paste. The purity of the obtained crystals was 41
It was 8.4%. Percent transmission was 513%.

Comparative Example 4 The crystals obtained in the same manner as in Comparative Example 2 were further recrystallized using water to obtain DL-phenylalanine crystals 2B and 5f. The isolated yield was 71.8 forms based on the product L-phenylalanine. The purity of the obtained crystals was 99.0
%Met. Percent transmission was 72%.

Comparative Example 5 2-chloro-3-phenylpropionic acid 55.41 (
0.3 mol) and 408f (6 mol) of 25M aqueous ammonia were placed in a 1000 m glass autoclave.
After heating to 5° C. and reacting for 6 hours, 0.5 g of activated carbon was added and stirred for 2 hours. After this, the waste coal is filtered and 40% hydroxyl is added.
After adding sodium mnaoy and recovering excess ammonia by distillation, the product was cooled and collapsed. z tt
It was separated with water and washed with cold methanol. In this way, DL-phenylalanine crystals 8B and 8W were obtained. The separation yield was 88.7% based on the product L-phenylalanine. The purity of the obtained crystal was 98.0%, and when 5 g of this crystal was dissolved in 100rnt of 2N hydrochloric acid and the transmission percentage of F80nnt was measured using a 10μ cell, it was 55% (t9). It was.

Comparative Example 6 Activated carbon instead of o and 5y! ;,'(The procedure was carried out in the same manner as in Comparative Example 8 except that 2,5f was used.

DL-phenylalanine's tJ crystal is 29.9 y. The isolated yield is 74% based on the product L-phenylalanine.
．． The purity of the obtained crystal was 99.0%.
In fact. Percent transmission was 80%.

Example 5 Methanol aoOrnt substitute) Methanol 600
The same procedure as in Example 1 was carried out except that +rt was used. DL
- 34.41 crystals of phenylalanine were obtained. The isolated yield was 86.7% based on raw, dDL-phenylalanine.

The purity of the obtained crystals was 99.8%.

Percent transmission was 96%.

Example 6 The same procedure as in Example 1 was carried out except that methanol 900- was used instead of methanol 800-. 34.4 crystals of DL-phenylalanine were obtained. The isolated yield is the product L-
The phenylalanine pace was 86.7%.

The purity of the obtained crystals was 99.8%.

Percent transmission was 96%.

Example 7 Ethanol 800r instead of methanol 800WLt
The same procedure as in Example 1 was conducted except that nt was used. 84.49 crystals of DL-phenylalanine were obtained. The separation yield was 86.4% based on the produced L-phenylalanine paste.

The purity of the obtained crystals was 99.5%.

Percent transmission was 94%.

Example 8 The same procedure as in Example 1 was carried out except that 1-propertool 800- was used instead of methanol 300-. Crystals 34.4j' of DL-phenylalanine were obtained. The separation yield was 86.5% based on the produced L-phenylalanine paste. The purity of the obtained crystals was 99.6%. Percent transmission was 9496.

<Effects of the Invention> As explained above, DL- obtained by reacting 2-chloro-8-phenylpropionic acid and aqueous ammonia
By adding a lower aliphatic alcohol to the reaction solution of phenylalanine and crystallizing DL-phenylalanine, it is possible to obtain DL-phenylalanine of high quality, particularly excellent color, in one step.

Claims (1)

[Claims] DL-phenylalanine, which is characterized in that a lower aliphatic alcohol is added to a reaction solution of DL-phenylalanine obtained by reacting 2-chloro-3-phenylpropionic acid and aqueous ammonia to crystallize DL-phenylalanine. purification separation method.