JP3065150B2 - Method for recovering methanol from aqueous esterification extract layer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for recovering methanol from an aqueous extraction layer after producing an amino acid methyl ester.

More specifically, a reaction solution in which an amino acid methyl ester is produced from an amino acid and methanol with a mineral acid catalyst is neutralized with an aqueous alkali solution, and after extracting the amino acid methyl ester with a water-insoluble organic solvent, the aqueous layer is treated with methanol. And a method for collecting the same.

[0003] Amino acids are constituent units of physiologically active substances such as proteins and peptides, and amino acid esters are useful as synthetic intermediates for these peptides. In particular, L-phenylalanine methyl ester has attracted attention as a main raw material of the artificial sweetener aspartame.

[0004]

2. Description of the Related Art Methyl esterification of amino acids has been known for a long time. JP-A-61-267600 discloses that a reaction solution obtained by esterifying an amino acid with methanol in the presence of a mineral acid catalyst is mixed with a basic aqueous solution for neutralizing the catalyst and water for extracting a free amino acid ester. It describes a method of adding an organic solvent and then using the amino acid ester in the separated organic solvent layer for the next reaction.

[0005]

However, in this method, the aqueous layer after the extraction of the amino acid ester contains a large amount of methanol, and if this methanol is discarded as waste water as it is, only the loss of raw material methanol occurs. However, there are problems such as high COD value and high cost of wastewater treatment.

[0006] Industrially, it is desired to recover and reuse methanol from the aqueous layer and to reduce the methanol content in wastewater.

[0007]

Means for Solving the Problems In order to solve the above problems, it has been studied to recover methanol by distillation.

In general, the balance of methanol to an organic layer and an aqueous layer after extraction of an amino acid methyl ester with an organic solvent depends on the type of the organic solvent used for the extraction. 15-30% is present in the organic layer.

[0009] The remaining methanol is considered to remain in the aqueous layer. However, when the methanol in the extracted aqueous layer is analyzed by gas chromatography (GC), only an analysis value lower than expected is obtained. The amount of methanol recovered by distillation from the aqueous layer was also small.

On the other hand, when the reaction solution obtained by esterifying the amino acid was neutralized, the neutralization was completed with about 2/3 equivalent of sodium hydroxide used for the esterification.

From the above facts, it was presumed that a part of the sulfuric acid and a part of the methanol reacted, and it was considered that the amount of methanol distilled and recovered from the extracted aqueous layer was small.

The present inventors have studied the conditions for recovering methanol from the aqueous layer. As a result, they have found that methanol can be efficiently recovered from the aqueous layer by adding a mineral acid catalyst to the aqueous layer and distilling it. The present invention has been completed.

According to the present invention, an amino acid and methanol are reacted with a mineral acid as a catalyst, a reaction solution in which an amino acid methyl ester is produced is neutralized with an aqueous alkali solution, and the amino acid methyl ester is extracted with an organic solvent. In a method for recovering methanol by distillation, a method for recovering methanol, which comprises performing distillation after adding an acid to an aqueous extraction layer,
It is.

According to the method of the present invention, methanol present in the extracted aqueous layer can be almost quantitatively recovered. Methanol can be recovered almost quantitatively.

The extraction aqueous layer containing methanol used in the present invention is obtained by esterifying an amino acid in methanol with a mineral acid as a catalyst, neutralizing with an aqueous alkali solution, and extracting with an organic solvent immiscible with water. Or an aqueous layer after neutralization with an aqueous alkali solution in the presence of an organic solvent immiscible with water and extraction with the organic solvent.

The amino acids used here are racemic,
Regardless of the optically active substance, for example, neutral α-amino acids such as glycine, alanine, valine, leucine, isoleucine, phenylalanine, serine, threonine, methionine, cysteine, tryptophan, proline, glutamine, asparagine, tyrosine, aspartic acid, and glutamic acid Acidic α-amino acids such as, lysine, arginine, basic α-amino acids such as histidine, β-phenylalanine,
β-aminopropionic acid, γ-aminobutyric acid and the like.

Mineral acids used as a catalyst for esterification include sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid and the like.

The water-immiscible organic solvent used as the extraction solvent in the present invention may be any solvent that can be separated from the aqueous layer containing the salt formed by neutralization after neutralization with a base. And hydrocarbons such as toluene, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride and 1,2 dichloroethane, and esters such as ethyl acetate and butyl acetate.

The base used for the neutralization of the present invention is
Sodium hydroxide, alkali metal hydroxides such as potassium hydroxide, sodium bicarbonate, alkali metal bicarbonates such as potassium bicarbonate, sodium carbonate, inorganic bases represented by alkali metal carbonates such as potassium carbonate, triethylamine, An organic base represented by a tertiary amine such as tributylamine may be mentioned, but an inorganic base which is not mixed with an organic solvent extraction layer of amino acid methyl ester is preferable.

The base, in the form of an aqueous solution, is added to a mixture of a reaction solution obtained by methyl esterification of an amino acid and a water-insoluble organic solvent,
Add with stirring. When a strong base such as an alkali metal hydroxide is used, hydrolysis of amino acid methyl ester due to local pH increase is suppressed.
It is added as an aqueous solution of not more than wt%.

The pH during neutralization is adjusted to 7.5. When the extraction operation of the amino acid ester is performed, the pH slightly decreases, but is adjusted to 7.5 each time.

In the present invention, the mineral acid added when recovering and distilling methanol includes sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, and the like. Sulfuric acid having no volatility and low corrosivity is preferable. The amount of the mineral acid to be added is preferably 1.8 mole ratio or more based on the amino acid used for the esterification. If the amount is less than this, a high recovery rate cannot be obtained. More preferably, the molar ratio is 2.2 or more.

It is preferable that the temperature at which methanol is distilled off is as high as possible.
The temperature should be raised to 00 ° C.

The pressure is sufficient at normal pressure, but in some cases, it can be carried out under pressure.

The mineral acid may be added before distillation, or may be added after methanol is distilled off to some extent. Further, it may be continuously added while distilling.

[0026]

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

Example 1 29.76 g of 98% sulfuric acid was added dropwise to a suspension of 27.31 g of L-phenylalanine (L-PA) and 54.5 g of methanol, and the mixture was reacted at 40 to 50 ° C. for 7 hours. An 8% aqueous sodium hydroxide solution was added dropwise to the obtained reaction mass, the pH was adjusted to 7.5, and 57.7 g of butyl acetate was added. Here, since the pH slightly dropped, the pH was adjusted again to 7.5 with an 8% aqueous NaOH solution, and the mixture was stirred for 30 minutes and allowed to stand for 30 minutes to separate two layers. The above separation operation was performed four times in total, and the butyl acetate layer 27 was removed.
5.5 g and 237.2 g of an aqueous layer were obtained. After treating the butyl acetate layer with an aqueous solution of sulfuric acid (L-phenylalanine methyl ester is hydrolyzed), GC analysis of methanol revealed that 22.6 g of methanol was present. Further, after a part of the extracted aqueous layer was diluted with a 5% aqueous sulfuric acid solution, and analyzed by GC (column temperature: 160 ° C., injection temperature: 180 ° C.), the aqueous layer contained 31.14 g of methanol. .

34.4 g of 98% sulfuric acid was added to the above extracted aqueous layer.
(2.2 molar ratio / L-PA) was added to distill off methanol. The pot temperature during distillation rose to 100 ° C. At this time,
The methanol distilled out was 31.11 g, and the recovery of methanol in the extracted aqueous layer was 99.86%. Also,
99% of the used methanol can be recovered including the extracted organic layer and the extracted aqueous layer.

Example 2 To 111.6 g of the methyl esterified mass of L-PA obtained by the same operation as in Example 1, 57.7 g of toluene was added, and an 8% aqueous NaOH solution was added dropwise to adjust the pH to 7.0. The mixture was stirred for 30 minutes and allowed to stand for 30 minutes to separate two layers. The above separation operation was performed three times in total, and 216 g of a toluene layer and 246.5 of an aqueous layer were obtained. As a result of GC analysis in the same manner as in Example 1, the amount of methanol in the aqueous layer was 37.16 g.
34.4 g of 98% sulfuric acid (2.2 mol ratio /
L-PA) was added to distill off methanol. The pot temperature during distillation rose to 100 ° C. At this time, 36.88 g of methanol was distilled off, and the recovery of methanol in the extracted aqueous layer was 98.07%. The unrecovered rate in the pot residue was 0.062%.

Example 3 To a suspension of 194.6 g of L-PA and 390.8 g of methanol, 211.86 g of 98% sulfuric acid was added and reacted at 45 to 50 ° C. for 7 hours. To this reaction mass, toluene 423.6 was added.
g was added thereto, and an 8% aqueous solution of NaOH was added dropwise to adjust the pH to 7.5. The mixture was stirred for 30 minutes and allowed to stand for 30 minutes to separate two layers.
This separation operation was performed four times in total, and 1895.1 g of a toluene layer was obtained.
And 1956.85 g of an aqueous layer were obtained. As a result of GC analysis in the same manner as in Example 1, the methanol concentration of the aqueous layer was 17.
It was 28 wt%.

[0031] 5.5% of 98% sulfuric acid was added to 101.6 g of the aqueous layer.
g (0.9 molar ratio / L-PA) was added to distill off methanol. The pot temperature during distillation rose to 100 ° C. As a result of analyzing the residue by gas chromatography, the recovery loss was 8.75%. The amount of methanol distilled was 15.86 g,
The recovery of methanol in the extracted aqueous layer was 90.33%.

Example 4 The esterified aqueous layer 10 obtained by the operation in Example 3
To 1.6 g, 11.0 g of 98% sulfuric acid (1.8 mol ratio / LP)
A) was added and methanol was distilled off. The pot temperature during distillation rose to 100 ° C. As a result of analyzing the bottom, the recovery loss was 0.970%.

Example 5 29.96 g of L-tyrosine (L-Tyr) and methanol 6
To 0.0 g of the suspension was added 29.76 g of 98% sulfuric acid,
The reaction was carried out at 50 ° C. for 7 hours. To the obtained esterified mass, 63.3 g of toluene was added, and an 8% aqueous NaOH solution was added dropwise to adjust the pH to 7.5. Then, the mixture was stirred for 30 minutes and allowed to stand for 30 minutes to separate two layers. This operation was performed four times in total, to obtain 283.1 g of a toluene layer and 236.04 g of an aqueous layer. As a result of GC analysis in the same manner as in Example 1, the methanol concentration in the aqueous layer was 17.50 wt%.

In the above aqueous layer, 41.19 g of 85% phosphoric acid (2.
2 mol ratio / L-Tyr) was added to distill off methanol. The pot temperature during distillation rose to 100 ° C. The amount of methanol distilled was 40.61 g, the recovery of methanol in the extracted aqueous layer was 98.32%, and the recovery was 0.53%.
Met.

COMPARATIVE EXAMPLE 100 g of the extracted aqueous layer after esterification obtained by the same operation as in Example 1 (13.49 g as methanol as determined by GC analysis as in Example 1) was distilled as it was. , Methanol was distilled off. The pot temperature during distillation rose to 100 ° C. Distilled methanol is 9.4
6 g, and the recovery rate reached only 70.12%.

[0036]

According to the present invention, it is possible to quantitatively recover methanol contained in an extraction water layer at the time of synthesizing an amino acid ester, thereby making it possible to reduce solvent recycling and wastewater treatment costs.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-4-112857 (JP, A) JP-A-61-267600 (JP, A) JP-A-3-47151 (JP, A) (58) Field (Int.Cl. ⁷ , DB name) C07C 229/36 B01D 3/34 C07C 29/84 C07C 31/04 C07C 227/40

Claims (4)

(57) [Claims] 1. An amino acid and methanol are reacted with a mineral acid as a catalyst to neutralize a reaction solution in which an amino acid methyl ester is produced with an aqueous alkali solution, and the amino acid methyl ester is extracted with an organic solvent. A method for recovering methanol, wherein a method for recovering by distillation comprises adding an acid to an aqueous extract layer and then performing distillation. 2. The method for recovering methanol according to claim 1, wherein the acid to be added is sulfuric acid. 3. The method for recovering methanol according to claim 1, wherein the acid to be added is at least 1.8 mole ratio to the amino acid used for the esterification. 4. The method according to claim 1, wherein the amino acid is L-phenylalanine.