JP2016210717A - Production process for n-acylamino acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a production process in which a high-purity N-acylamino acid having a good color tone can be produced with high yield.SOLUTION: A production process for N-acylamino acid is provided in which an acylation reaction between an amino acid represented by formula (1) and a fatty acid chloride having a carbon number of 16 to 22 is performed in a mixed solvent between a water and an organic solvent and having an octanol/water partition coefficient of 1.6 to 3.5 under an alkali condition. (In the formula (1), Rrepresents a hydrogen atom or a methyl group, Rrepresents a hydrogen atom or an alkali metal atom, and n represents an integer of 1 or 2.).SELECTED DRAWING: None

Description

  The present invention relates to a method for producing an N-acylamino acid.

As a method for producing an N-acylamino acid, a method in which an amino acid and a fatty acid chloride are reacted by a Schotten-Baumann reaction under an alkaline condition and then isolated as an N-acylamino acid using an acid is generally known. Yes.
For the production of acylamino acids, it is known that the reaction proceeds even when only water is used as a solvent. However, when the acyl group is a long chain, reaction with water as a solvent causes formation of products and salts. Since the reaction solution is thickened, stirring is insufficient particularly when the reaction is performed at a high concentration, and a fatty acid production reaction as a side reaction is likely to occur.
On the other hand, even when the amount of water as a solvent is increased in order to suppress an increase in viscosity and the reaction is carried out at a low concentration, the production of fatty acid as a side reaction is promoted.
For this reason, various attempts have been made to increase the purity of N-acylamino acids.

  For example, Patent Document 1 discloses a method in which β-alanine and a long-chain fatty acid chloride are reacted with water as a solvent in the presence of potassium hydroxide. In this method, potassium hydroxide is used to increase the solubility of the product in water, and the increase in viscosity is suppressed by setting the reaction temperature as high as 60 to 90 ° C. However, since the reaction temperature is high in this method, the hue of the resulting product may be deteriorated. In applications such as cleaning agents, the hue of the acylamino acid may affect the hue of the product, so a good hue is desired.

In addition, attempts have been made to suppress an increase in the viscosity of the reaction solution by using a homogeneous mixed solvent of water and a hydrophilic organic solvent as the reaction solvent. For example, in Patent Document 2, when an acidic amino acid and a long-chain fatty acid chloride are condensed in the presence of an alkali, a mixed solvent of water and a hydrophilic organic solvent such as acetone, methyl ethyl ketone, dioxane, and tetrahydrofuran is used as a reaction solvent. Thus, it is disclosed that an N-long chain acyl acidic amino acid can be obtained in high yield.
Patent Document 3 discloses a method for increasing the purity of an N-long chain acyl neutral amino acid by reacting a neutral amino acid and a fatty acid chloride in a mixture of a hydrophilic organic solvent and water in the presence of a base. Is disclosed.
However, since a hydrophilic solvent is used in these methods, a part of the product may be dissolved in the aqueous layer in the purification process, and the yield may be reduced. Furthermore, since a part of the product is dissolved in the aqueous layer, an emulsion layer of water, a hydrophilic organic solvent mixture and the product may be formed, and thus the yield may be reduced by separating the emulsion layer. is there. Moreover, when it heats in order to cancel | release emulsification, a yield fall will be suppressed, but a hue may deteriorate.

  Thus, it is difficult to obtain a high-purity N-acylamino acid having a good hue in a high yield by the conventional technique, and a N-acylamino acid having a good hue and purity can be obtained in a high yield. A new method was sought.

Japanese Patent Laid-Open No. 5-70418 Japanese Patent Publication No.46-8865 JP 2003-221371 A

  An object of this invention is to provide the manufacturing method which can obtain the highly purified N-acylamino acid which has a favorable hue with a high yield.

  As a result of intensive studies to solve the above problems, the present inventors have a predetermined octanol / water partition coefficient when acylating a specific amino acid and a specific fatty acid chloride under alkaline conditions. It has been found that the above problem can be solved by carrying out the reaction in a mixed solvent of an organic solvent and water, and the present invention has been completed.

（式（１）中、Ｒ^１は水素原子またはメチル基を示し、Ｒ^２は水素原子またはアルカリ金属原子を示し、ｎは１または２の整数を示す。） That is, the present invention provides a mixed solvent of an organic solvent and water having an octanol / water partition coefficient of 1.6 to 3.5, the amino acid represented by the formula (1) and a fatty acid chloride having 16 to 22 carbon atoms. A method for producing an N-acylamino acid, characterized by carrying out an acylation reaction under alkaline conditions.

(In formula (1), R ¹ represents a hydrogen atom or a methyl group, R ² represents a hydrogen atom or an alkali metal atom, and n represents an integer of 1 or 2.)

  According to the production method of the present invention, a highly pure N-acylamino acid having a good hue is produced in high yield from the amino acid represented by the formula (1) and a fatty acid chloride having 16 to 22 carbon atoms. Can do.

Hereinafter, embodiments of the present invention will be described.
In the production method of the present invention, a specific amino acid and a specific fatty acid chloride are acylated in a mixed solvent of an organic solvent and water having an octanol / water partition coefficient of 1.6 to 3.5 under alkaline conditions. The reaction is characterized by having at least an acylation step described later. Further, usually, the target N-acylamino acid is produced through a separation step, a water washing step and a solvent distillation step after the acylation step.

The amino acid used in the present invention is an amino acid represented by the formula (1). In the formula, R ¹ represents a hydrogen atom or a methyl group, preferably a methyl group. R ² represents a hydrogen atom or an alkali metal atom. Examples of the alkali metal include lithium, sodium, potassium, and the like, preferably sodium or potassium. n represents an integer of 1 or 2. Specific examples of the amino acid represented by the formula (1) include glycine, N-methylglycine (hereinafter also referred to as sarcosine), β-alanine, and N-methyl-β-alanine.

  The fatty acid chloride to be reacted with the amino acid represented by the formula (1) is a chloride of a saturated or unsaturated fatty acid having 16 to 22 carbon atoms. The carbon chain of the fatty acid may be linear, branched, or a combination thereof, and may contain one or more unsaturated bonds. Examples of the fatty acid chloride include palmitic acid chloride, isopalmitic acid chloride, stearic acid chloride, isostearic acid chloride, oleic acid chloride, linoleic acid chloride, linolenic acid chloride, behenic acid chloride, erucic acid chloride, and the like. Preferred are unsaturated fatty acid chlorides such as oleic acid chloride and erucic acid chloride.

The organic solvent used in the present invention has a predetermined octanol / water partition coefficient (P _ow ). The octanol / water partition coefficient (P _ow ) is a ratio of equilibrium concentrations of substances dissolved in two phases composed of two immiscible solvents. In the present invention, Japanese Industrial Standard (JIS Z 7260-107 (2000) ) Distribution coefficient (1-octanol / water)-a value measured by a flask shaking method.
In the present invention, the organic solvent used for the reaction by mixing with water has a P _ow of 1.6 to 3.5. If an organic solvent having an excessively small _Pow is used, it will be miscible with the aqueous phase and an emulsion layer will be formed, which may lead to a decrease in yield. Degradation of purity and deterioration of hue may occur due to decomposition. If an organic solvent having an excessively large _Pow is used, the generation reaction of fatty acid, which is a side reaction, easily occurs, resulting in a decrease in purity, or the unreacted amino acid dissolves in the aqueous phase during oil-water separation. The rate may be reduced.
Examples of the organic solvent having P _ow of 1.6 to 3.5 include chloroform (P _ow = 1.97), benzene (P _ow = 2.13), isoprene (P _ow = 2.42), toluene ( _Pow = 2.69), chlorobenzene ( _Pow = 2.89), terpineol ( _Pow = 2.98), ethylbenzene ( _Pow = 3.15), cyclohexane ( _Pow = 3.44), etc. Can be mentioned. A preferred range of P _ow is 2.0 to 3.3, more preferred range is 2.4 to 3.2, particularly preferred range is 2.6 to 3.0. Preferable organic solvents include, for example, toluene and terpineol, more preferably toluene.

The amount of water in the mixed solvent in the acylation reaction is preferably 2 to 10 parts by mass, more preferably 4 to 8 parts by mass with respect to 1 part by mass of the amino acid of formula (1) to be subjected to the reaction.
Further, the amount of the organic solvent in the mixed solvent in the acylation reaction is preferably 0.05 to 1, more preferably 0.1 to 0.25 in terms of a mass ratio (organic solvent / water) to water used in the reaction. It is.

(Acylation step)
In the present invention, the acylation reaction is carried out under alkaline conditions, preferably in a reaction solution having a pH of 10 to 14. Examples of the method for bringing the reaction solution into an alkaline condition include a method in which an alkali compound is present in the reaction solution. For example, the amino acid represented by the formula (1) is dissolved in the presence of water, an organic solvent and an alkali compound, and fatty acid chloride is dropped into the reaction solution.
Examples of the alkali compound to be used include sodium hydroxide, potassium hydroxide, sodium carbonate, ammonia and the like.
In the present invention, the reaction temperature of the acylation reaction is not particularly limited, but is preferably in the range of 0 to 50 ° C., more preferably 10 to 40 ° C., from the viewpoint of the progress of the reaction and the hue of the target substance.
Regarding the use ratio of the amino acid represented by the formula (1) and the fatty acid chloride, the former is preferably used in the same mole or more with respect to the latter in order to obtain the target substance in high yield. That is, the use ratio (amino acid / fatty acid chloride molar ratio) of the amino acid of the formula (1) to the fatty acid chloride is preferably in the range of 1.0 to 1.5.

  In carrying out the reaction, a method in which the amino acid represented by the formula (1) is dissolved in water and an organic solvent and then the fatty acid chloride is gradually added dropwise with stirring in order to increase the reaction rate. Although the reaction time varies depending on various conditions, the dropping time of fatty acid chloride is usually about 30 minutes to 6 hours, and the reaction time after dropping is usually about 10 minutes to 4 hours.

(Layer separation process)
After completion of the reaction, the reaction mixture is acidified with a mineral acid such as sulfuric acid and hydrochloric acid, and the temperature is raised to about 60 to 80 ° C. Thereafter, the stirring is stopped, and the mixture is allowed to stand while maintaining the temperature for about 10 minutes to 1 hour to separate into an organic phase and an aqueous phase, and the organic phase is separated therefrom.

(Washing process)
To the separated organic phase, 5 to 10% by mass of an acidic aqueous solution such as sulfuric acid, hydrochloric acid or citric acid is added to 70 to 90% by mass with respect to the mass of the organic phase, and the temperature is raised to about 60 to 80 ° C. with stirring. . Thereafter, the stirring is stopped, and the mixture is allowed to stand while maintaining the temperature for about 10 minutes to 1 hour, and is separated into an organic phase and an aqueous phase. In order to reduce the remaining alkali metal, the same operation may be performed a plurality of times on the separated organic phase.

(Solvent distillation step)
In order to distill off water and the organic solvent from the separated organic phase, the distillation is usually performed by heating to 40 to 100 ° C. If necessary, distillation can be performed under reduced pressure.

[Examples 1 to 5 and Comparative Examples 1 to 4]
Hereinafter, it demonstrates further more concretely by an Example and a comparative example. In addition, the N-acylamino acids obtained in Examples and Comparative Examples were analyzed as follows.

(1) Yield Yield is the theoretical amount of N-acylamino acid relative to the fatty acid chloride used in the reaction.

(2) Free fatty acid content The amount of free fatty acid contained was measured by gas chromatography (Shimadzu Corporation, GC-2014) using an FID detector under the conditions shown in Table 1 below. It was. The column used was OV-1 (packed column).

  A measurement sample was prepared by trimethylsilylation using 1,1,1,3,3,3-hexamethyldisilazane and trimethylchlorosilane, and measurement was performed.

(3) Purity Purity was a value obtained by subtracting the free fatty acid content from 100% by mass.

(4) Hue Hue was measured according to the Gardner method of JOCS (Established by the Japan Oil Chemists' Society, Standard Oil Analysis Test) 2.2.1.3. In addition, it is so preferable that a numerical value is small, 4 or less are preferable with a Gardner, and 3 or less are more preferable.

[Example 1]
(Acylation step)
138.7 g (0.50 mol) of 40% by weight aqueous sarcosine sodium solution, 167.7 g of water, 57.9 g of 24% by weight aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide), toluene (P _ow = 2.69) ) 72.1 g (0.24 mol) of oleic acid chloride was added dropwise over 30 minutes while cooling to 33.6 g of the mixed solution. Thereafter, the mixture was reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide) was added, and 72.1 g (0.24 mol) of oleic acid chloride was added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.

(Layer separation process)
62. A 5% by mass sulfuric acid aqueous solution was added dropwise to bring the pH of the solution to 2, and the temperature of the solution was adjusted to 70 ° C. After completion of the dropwise addition, the stirring was stopped and the mixture was allowed to stand at 70 ° C. for 30 minutes.

(Washing process)
To the separated organic phase, 180.3 g of an aqueous 5.5% by mass citric acid solution was added and stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase. To the separated organic phase, 180.3 g of an aqueous 5.5% by mass citric acid solution was added and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.

(Solvent distillation step)
The separated and obtained organic phase was distilled under reduced pressure at 60 ° C. under a pressure of 30 mmHg.
The yield of the obtained N-oleoyl sarcosine was 97.8% by mass, the free fatty acid content was 2.1% by mass, the purity was 97.9% by mass, and the hue was 4 by Gardner.

[Example 2]
It implemented by the same method as the acylation process of Example 1, a layer separation process, and the water washing process except having changed the organic solvent to be used into terpineol ( _Pow = 2.98). In the solvent distillation step, the separated and obtained organic phase was distilled under reduced pressure at 80 ° C. under a pressure of 10 mmHg.
The yield of the obtained N-oleoyl sarcosine was 96.5% by mass, the free fatty acid content was 4.7% by mass, the purity was 95.3% by mass, and the hue was 4 by Gardner.

Example 3
(Acylation step)
37 mass% N-methyl-β-alanine sodium aqueous solution 126.8 g (0.38 mol), water 120.3 g, 24 mass% sodium hydroxide aqueous solution 43.4 g (sodium hydroxide 0.26 mol), toluene (P _ow = 2.69) 54.0 g (0.18 mol) of oleic acid chloride was dropped into the mixed solution of 24.1 g over 30 minutes while cooling. Thereafter, the mixture is reacted at 30 ° C. for 15 minutes, 43.4 g of a 24 mass% sodium hydroxide aqueous solution (0.26 mol of sodium hydroxide) is added, and 54.0 g (0.18 mol) of oleic acid chloride is added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.

(Layer separation process)
The same method as in Example 1 was performed.

(Washing process)
To the separated organic phase was added 139.2 g of an aqueous 5.5% by mass citric acid solution, and the mixture was stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase. To the separated organic phase was added 139.2 g of an aqueous 5.5% by mass citric acid solution, and the mixture was stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.

(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of N-oleoyl-N-methyl-β-alanine obtained was 97.1% by mass, the free fatty acid content was 2.8% by mass, the purity was 97.2% by mass, and the hue was 4 by Gardner. It was.

Example 4
(Acylation step)
138.7 g (0.50 mol) of 40% by weight aqueous sarcosine sodium solution, 167.7 g of water, 57.9 g of 24% by weight aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide), toluene (P _ow = 2.69) ) 66.0 g (0.24 mol) of palmitic acid chloride was added dropwise to the 33.6 g mixed solution over 30 minutes while cooling. Thereafter, the mixture was reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% sodium hydroxide aqueous solution (0.35 mol of sodium hydroxide) was added, and 66.0 g (0.24 mol) of palmitic acid chloride was added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.

(Layer separation process)
The same method as in Example 1 was performed.

(Washing process)
To the separated organic phase, 5.5 wt% citric acid aqueous solution (166.9 g) was added and stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase. To the separated organic phase, 5.5 wt% citric acid aqueous solution (166.9 g) was added and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.

(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of the obtained N-palmitoyl sarcosine was 96.2% by mass, the free fatty acid content was 4.9% by mass, the purity was 95.1% by mass, and the hue was 3 by Gardner.

Example 5
(Acylation step)
A mixed solution of 44.5 g (0.50 mol) of sarcosine, 178.6 g of water, 141.6 g of a 24% by mass aqueous sodium hydroxide solution (0.85 mol of sodium hydroxide), and 33.6 g of toluene (P _ow = 2.69) While cooling, 85.7 g (0.24 mol) of erucic acid chloride was added dropwise over 30 minutes. Thereafter, the mixture is reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide) is added, and 85.7 g (0.24 mol) of erucic acid chloride is added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.

(Layer separation process)
The same method as in Example 1 was performed.

(Washing process)
To the separated organic phase was added 202.7 g of an aqueous 5.5% by mass citric acid solution and stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase. To the separated organic phase was added 202.7 g of an aqueous 5.5% by mass citric acid solution and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.

(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of the obtained N-ercaroyl sarcosine was 96.7% by mass, the free fatty acid content was 4.4% by mass, the purity was 95.6% by mass, and the hue was 4 by Gardner.

[Comparative Example 1]
(Acylation step)
138.7 g (0.50 mol) of 40% by mass aqueous sodium sarcosine solution, 167.7 g of water, 57.9 g of 24% by mass aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide), acetone (P _ow = −0.0. 24) 72.1 g (0.24 mol) of oleic acid chloride was added dropwise to the mixed solution of 33.6 g over 30 minutes while cooling. Thereafter, the mixture was reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide) was added, and 72.1 g (0.24 mol) of oleic acid chloride was added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.

(Layer separation process)
A 62.5 mass% sulfuric acid aqueous solution was dropped to adjust the pH of the solution to 2 and the temperature of the solution was adjusted to 70 ° C. After completion of the dropwise addition, stirring was stopped and the mixture was allowed to stand at 80 ° C. for 1 hour, so that the organic phase and the aqueous phase were separated, and the organic phase was separated therefrom.

(Washing process)
To the separated organic phase, 150.3 g of an aqueous 5.5% by mass citric acid solution was added and stirred for 15 minutes. When the stirring was stopped, the mixture was allowed to stand at 80 ° C. for 1 hour, and the organic phase and the aqueous phase were separated. To the separated organic phase, 150.3 g of an aqueous 5.5% by mass citric acid solution was added and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 80 ° C. for 1 hour to separate into an organic phase and an aqueous phase, and then the organic phase was separated.

(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of the obtained N-oleoyl sarcosine was 92.5% by mass, the free fatty acid content was 6.5% by mass, the purity was 93.5% by mass, and the hue was 5 by Gardner.

[Comparative Example 2]
N-oleoyl sarcosine was obtained in the same manner as in Comparative Example 1 except that the organic solvent used was changed to tertiary butanol (P _ow = 0.37). The yield of the obtained N-oleoyl sarcosine was 91.6% by mass, the free fatty acid content was 7.2% by mass, the purity was 92.8% by mass, and the hue was 5 by Gardner.

[Comparative Example 3]
(Acylation step)
138.7 g (0.50 mol) of 40% by weight aqueous sarcosine sodium solution, 167.7 g of water, 57.9 g of 24% by weight aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide), 1,2-dichloroethane (P _ow = 1.48) 72.1 g (0.24 mol) of oleic acid chloride was added dropwise to 33.6 g of the mixed solution over 30 minutes while cooling. Thereafter, the mixture was reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide) was added, and 72.1 g (0.24 mol) of oleic acid chloride was added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.

(Layer separation process)
A 62.5 mass% sulfuric acid aqueous solution was dropped to adjust the pH of the solution to 2 and the temperature of the solution was adjusted to 70 ° C. After completion of the dropwise addition, stirring was stopped and the mixture was allowed to stand at 70 ° C. for 30 minutes, so that the organic phase and the aqueous phase were separated, and the organic phase was separated therefrom.

(Washing process)
178.8 g of 5.5 mass% citric acid aqueous solution was added to the separated organic phase and stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 80 ° C. for 30 minutes, and the organic phase and the aqueous phase were separated. 178.8 g of 5.5 mass% citric acid aqueous solution was added to the separated organic phase and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 80 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.

(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of the obtained N-oleoyl sarcosine was 91.0% by mass, the free fatty acid content was 6.8% by mass, the purity was 93.2% by mass, and the hue was 4 by Gardner.

[Comparative Example 4]
N-oleoyl sarcosine was obtained in the same manner as in Example 1 except that the organic solvent used was changed to methylcyclohexane (P _ow = 3.61). The yield of the obtained N-oleoyl sarcosine was 89.7% by mass, the free fatty acid content was 43.1% by mass, the purity was 56.9% by mass, and the hue was 4 by Gardner.

  Table 3 summarizes the organic solvent, amino acid, fatty acid chloride, and various analysis values used for the above results. Table 2 shows the relationship between the amino acids used and the various symbols in formula (1).

Examples 1-5 were good results in all items.
On the other hand, in Comparative Examples 1 to 3, _{Pow of} the organic solvent used was less than 1.6, so the purity decreased and the hue deteriorated. In Comparative Example 4, _{Pow of} the organic solvent used was 3.5. As a result, the yield and purity decreased.

Claims (1)

An amino acid represented by the formula (1) and a fatty acid chloride having 16 to 22 carbon atoms are subjected to alkaline conditions in a mixed solvent of an organic solvent and water having an octanol / water partition coefficient of 1.6 to 3.5. And a method for producing an N-acylamino acid, characterized by carrying out an acylation reaction.

(In formula (1), R ¹ represents a hydrogen atom or a methyl group, R ² represents a hydrogen atom or an alkali metal atom, and n represents an integer of 1 or 2.)