JP5336904B2 - Method for producing carboxylic acid - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a carboxylic acid from an aqueous solution of a crude carboxylic acid containing a carboxylic acid amide as an impurity, especially a method for improving the quality of the finally produced carboxylic acid by converting into an ammonium carboxylate the carboxylic acid amide contained as a reaction byproduct in the aqueous solution of the crude carboxylic acid obtained by desalting an aqueous solution of ammonium carboxylate obtained by the hydrolysis of a nitrile compound. <P>SOLUTION: The aqueous solution of the high-quality carboxylic acid can be obtained by bringing the aqueous solution of the crude carboxylic acid containing the carboxylic acid amide as the impurity into contact with a solid acid catalyst to hydrolyze the carboxylic acid amide. Especially, the hydrolysis of the carboxylic acid amide can efficiently be carried out by decreasing the ammonium carboxylate corresponding to the carboxylic acid contained in the aqueous solution of the crude carboxylic acid. <P>COPYRIGHT: (C)2011,JPO&amp;INPIT

Description

  The present invention relates to a method for producing a carboxylic acid from a crude carboxylic acid aqueous solution containing a carboxylic acid amide as an impurity. In particular, the present invention relates to carboxylic acid amide contained as a reaction by-product in a crude carboxylic acid aqueous solution obtained by desalting an aqueous carboxylic acid ammonium salt solution obtained by hydrolysis of a nitrile compound. It is related with the manufacturing method of carboxylic acid which can make the quality of the carboxylic acid finally manufactured high by converting into.

  Among various methods for producing carboxylic acids, several are known as intermediates via ammonium carboxylate. For example, when carboxylic acid is produced by fermentation, when ammonia water is used for pH control during fermentation, the substance obtained by fermentation production is ammonium carboxylate (Patent Document 1). Moreover, when manufacturing carboxylic acid using a nitrile compound as a starting material, the substance obtained by the hydrolysis reaction using enzymes, such as nitrilase, is ammonium carboxylate (patent document 2). There is also an example of producing ammonium carboxylate by hydrolyzing a nitrile compound in one step using a metal catalyst (Patent Document 3).

  Such aqueous carboxylic acid ammonium salt solutions may contain carboxylic acid amides as impurities. For example, when carboxylic acid is produced using a nitrile compound as a starting material and microbial cells as a catalyst, carboxylic acid amides are produced if nitrile hydratase is present in the microbial cells (Patent Document 4). In addition, even if the microbial cell catalyst is nitrilase, the carboxylic acid amide, which is an intermediate of the hydrolysis reaction, is produced as a by-product even though it originally has catalytic ability to convert to ammonium carboxylate. (Non-Patent Document 1). Furthermore, in the hydrolysis using a metal catalyst, as long as the examples are seen, by-product formation of carboxylic acid amide is inevitable (Patent Document 3).

  Various methods for treating the by-product carboxylic acid amide are also known. For example, a method for thermally decomposing carboxylic acid amide while preventing the formation of carboxylic acid amide by reaction of carboxylic acid with ammonia has been shown (Patent Document 5). There is a problem that it is essential and the process becomes complicated.

  As another method, an acidic catalyst is used to hydrolyze the carboxylic acid amide, but since an ammonium salt of the acidic catalyst is always produced, in order not to make the ammonium salt a waste, It was complicated because it was necessary to regenerate using a method such as electrodialysis. (Patent Document 6) Further, a method of hydrolyzing a carboxylic acid amide using an alkali catalyst such as an alkali metal salt is disclosed (Patent Document 6), but a step of desalting the produced carboxylic acid metal salt is also included. It was necessary and further simplification was desired.

JP 2007-124931 A JP 2005-504506 A JP 2006-522755 A JP 2004-81169 A EP1385593 JP-A-8-245495

Adv. Synth. Catal., 348, 2597-2603 (2006)

  The subject of this invention is providing the method of manufacturing carboxylic acid from the crude carboxylic acid aqueous solution which contains carboxylic amide as an impurity. The problem of the present invention is that, in particular, a carboxylic acid amide contained as a reaction by-product in a crude carboxylic acid aqueous solution obtained by desalting an aqueous carboxylic acid ammonium salt solution obtained by a hydrolysis reaction of a nitrile compound, An object of the present invention is to provide a method for producing a carboxylic acid capable of improving the quality of the carboxylic acid finally produced by converting it to ammonium acid.

  The inventors of the present invention have made extensive studies on a method for reducing the carboxylic acid amide in producing a carboxylic acid from a crude carboxylic acid aqueous solution containing the carboxylic acid amide as an impurity. It has been found that the carboxylic acid amide present in the carboxylic acid aqueous solution is hydrolyzed catalytically by contacting the acid aqueous solution with a solid acid catalyst. Based on this knowledge, the present inventors have further studied the hydrolysis of the carboxylic acid amide, and as the amount of the carboxylic acid ammonium salt corresponding to the carboxylic acid contained in the crude carboxylic acid aqueous solution decreases. The present inventors have found that the hydrolysis reaction of the carboxylic acid amide proceeds efficiently, and found that the quality of the aqueous carboxylic acid solution thus obtained is very high, thereby completing the present invention.

That is, the present invention has a configuration as described below.
(1) A method for producing a carboxylic acid, comprising a step of hydrolyzing the carboxylic acid amide by bringing a crude carboxylic acid aqueous solution containing the carboxylic acid amide into contact with a solid acid catalyst.
(2) A method for producing a carboxylic acid, comprising a step of hydrolyzing the carboxylic acid amide by contacting with a solid acid catalyst after desalting an aqueous solution of a crude carboxylic acid ammonium salt containing the carboxylic acid amide.
(3) The method for producing a carboxylic acid according to (1) or (2), wherein in the step of hydrolyzing the carboxylic acid amide, the carboxylic acid amide is reduced to 500 [weight ppm / carboxylic acid] or less.
(4) The method for producing a carboxylic acid according to any one of (1) to (3), wherein the crude carboxylic acid aqueous solution is obtained by a hydrolysis reaction of a corresponding nitrile compound.
(5) The method for producing a carboxylic acid according to (4), wherein the hydrolysis of the nitrile compound is performed as an enzyme catalyst by nitrilase and / or a combination of nitrile hydratase and amidase.
(6) The method for producing a carboxylic acid according to (4), wherein the hydrolysis of the nitrile compound is performed by nitrilase.
(7) The method for producing a carboxylic acid according to (5) or (6), wherein the nitrilase is derived from the genus Acinetobacter.
(8) The method for producing a carboxylic acid according to (7), wherein the Acinetobacter genus is Acinetobacter sp. AK226.
(9) Any one of (1) to (8), wherein the solid acid catalyst is one or more selected from the group consisting of zeolite, strongly acidic cation exchange resin, heteropolyacid salt, and layered metal oxide. The manufacturing method of carboxylic acid as described in a term.
(10) The solid acid catalyst is a strongly acidic cation exchange resin, and in the step of hydrolyzing the carboxylic acid amide, an ammonium carboxylate salt is produced by the hydrolysis reaction of the carboxylic acid amide by the solid acid catalyst used. The method for producing a carboxylic acid according to any one of (1) to (9), wherein at the same time, the ammonium carboxylate is converted into a carboxylic acid and an impurity cation is removed.
(11) The method for producing a carboxylic acid according to (10), further comprising a step of removing impurity anions with an anion exchange resin after the step of producing the carboxylic acid.
(12) The production of the carboxylic acid according to (10), further comprising a step of removing impurity anions with an anion exchange resin and a step of removing impurity cations with a cation exchange resin after the step of producing the carboxylic acid. Method.
(13) The method for producing an α-hydroxy acid according to any one of (1) to (12), wherein the carboxylic acid is an α-hydroxy acid.
(14) The method for producing an α-hydroxy acid according to (13), wherein the α-hydroxy acid is lactic acid or glycolic acid.
(15) The method for producing an α-hydroxy acid according to (13), wherein the α-hydroxy acid is glycolic acid.
(16) A step of synthesizing an α-hydroxy acid oligomer using an aqueous solution of α-hydroxy acid obtained by the method according to any one of (13) to (15) as a raw material, and the α-hydroxy acid oligomer And depolymerizing to obtain the cyclic dimer ester. A method for producing the cyclic dimer ester.
(17) A method for producing a poly α-hydroxy acid, comprising a step of obtaining a poly α-hydroxy acid by a ring-opening polymerization reaction using the cyclic dimer ester obtained by the method according to (16) as a raw material.

  The present invention can provide a method for producing a carboxylic acid from a crude carboxylic acid aqueous solution containing a carboxylic acid amide as an impurity. In particular, the present invention provides a carboxylic acid amide contained as a reaction by-product in a crude carboxylic acid aqueous solution obtained by desalting an aqueous carboxylic acid ammonium salt solution obtained by hydrolysis of a nitrile compound. By converting to ammonium, it is possible to provide a method for producing a carboxylic acid capable of improving the quality of the finally produced carboxylic acid.

FIG. 1 is a schematic diagram showing an example of a membrane structure of a typical electrodialysis apparatus used in the present invention. FIG. 2 is a production process diagram showing an example of a method for producing a carboxylic acid in the present invention. FIG. 3 is a production process diagram showing another example of the method for producing carboxylic acid according to the present invention. FIG. 4 is a production process diagram showing another example of the method for producing carboxylic acid in the present invention. FIG. 5 shows the results of changes over time in Examples 1 to 4 and Comparative Examples 1 to 3. FIG. 6 shows the result of breakthrough curve in Example 18.

1 Nitrile Compound Supply Line 2 Hydrolysis Reaction Mixture Supply Line 3 Electrodialysis Process Acid Chamber Recovery Carboxylic Acid Mixture Supply Line 4 Electrodialysis Process Base Chamber Ammonia Mixture Recovery Line 5 Electrodialysis Process Base Chamber Ammonia Mixture Circulation Line 6 Electricity Dialysis process base chamber ammonia mixture separation and recovery line 7 Carboxylic acid mixture supply line after deamidation reaction Carboxylic acid mixture supply line 9, 15, 19 after anion exchange purification process Anion exchange purification process washing and regeneration / reverse regeneration liquid recovery Line 10 Carboxylic acid mixture recovery line after cation exchange purification process 11 Cation exchange purification process washing liquid and regeneration / reverse regeneration liquid recovery line 12 Carboxylic acid mixture supply line after α cation exchange 13 Washing liquid after regeneration and reverse regeneration liquid Recovery lines 14, 18 After anion exchange purification process Bon acid mixture recovery line 16 beta cation exchange after acid mixture supply line 17 beta after cation exchange wash and regeneration, reverse regeneration liquid recovery line

The present invention will be specifically described below.
In the present invention, the carboxylic acid common to the three of carboxylic acid, carboxylic acid amide, and ammonium carboxylate is not particularly limited, and can be selected from a wide range of compounds. An exemplary carboxylic acid can be represented by the formula RCOOH. (In the formula, R represents a hydrogen atom, an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an aromatic hydrocarbon group, a heterocyclic group, etc., and these groups may further have a substituent) . The carboxylic acid includes polycarboxylic acids such as dicarboxylic acid and tricarboxylic acid. That is, the aliphatic hydrocarbon group, alicyclic hydrocarbon group, aromatic hydrocarbon group, and heterocyclic group are not limited to monovalent groups, and may be divalent or higher polyvalent groups.

  The aliphatic hydrocarbon group may be a saturated hydrocarbon group such as, for example, methyl, ethyl, propyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, octyl, decyl, etc. Alkyl group or unsaturated hydrocarbon group of about 1 to 12 (preferably 1 to 6), for example, specifically, about 2 to 12 carbon atoms such as vinyl, allyl, 1-propenyl, isopropenyl, 2-butenyl, etc. Alkenyl groups, ethynyl, 2-propynyl and the like alkynyl groups having about 2 to 12 carbon atoms, and alkylene groups having about 2 to 12 carbon atoms.

  Specific examples of the alicyclic hydrocarbon group include cycloalkyl groups having about 3 to 10 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, and cycloalkylene groups corresponding to these. Specific examples of the aromatic hydrocarbon group included include aryl groups having about 6 to 14 carbon atoms such as phenyl and naphthyl, and arylene groups corresponding to these aryl groups.

  Specific examples of the heterocyclic group include a heterocyclic group containing at least one atom selected from nitrogen, oxygen, and sulfur atoms as a hetero atom. The heterocyclic group may be any of an aromatic heterocyclic group, a non-aromatic heterocyclic group, and a condensed heterocyclic group. Specific examples of the heterocyclic group include furyl, thienyl, pyrrolyl, pyrrolidinyl, pyridyl, pyrazinyl, pyrimidyl, pyridazinyl, piperidino, morpholino, morpholinyl, and quinolyl groups.

  These groups represented by R further include a halogen atom, a hydroxyl group, an alkyl group (such as an alkyl group having 1 to 5 carbon atoms such as methyl, ethyl, propyl, isopropyl, etc.), an aryl group (phenyl, tolyl, xylyl, chlorophenyl). , Aryl groups having 6 to 14 carbon atoms such as methoxyphenyl and naphthyl), ether groups, alkoxy groups (for example, alkoxy groups having 1 to 5 carbon atoms such as methoxy and ethoxy), aryloxy groups (for example, phenoxy and the like) An aryloxy group having 6 to 14 carbon atoms, etc.), a mercapto group, an alkylthio group (for example, an alkylthio group having 1 to 5 carbon atoms such as methylthio and ethylthio), an arylthio group (for example, 6 to 14 carbon atoms such as phenylthio). Arylthio group, etc.), carboxyl group, ester group (for example, carbon such as methoxycarbonyl) 1 to 6 alkoxycarbonyl groups, acyloxy groups having 2 to 12 carbon atoms such as acetoxy), acyl groups (for example, acyl groups having 2 to 12 carbon atoms such as acetyl and benzoyl), amino groups, mono or di It may have a substituent such as a substituted amino group (for example, a mono- or di-substituted alkylamino group having 1 to 5 carbon atoms such as methylamino or dimethylamino), a nitro group, or the like. Of these, α-hydroxycarboxylic acid is particularly preferable.

Aliphatic carboxylic acids include, for example, saturated or unsaturated carboxylic acids having 2 to 6 carbon atoms (saturated carboxylic acids such as acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, malonic acid, succinic acid, Saturated dicarboxylic acids such as glutaric acid and adipic acid, and unsaturated carboxylic acids such as acrylic acid, methacrylic acid, allyl acetic acid and crotonic acid).
Examples of the alicyclic carboxylic acid include carboxylic acids having 4 to 10 carbon atoms (cyclopentanecarboxylic acid, cyclohexanecarboxylic acid, etc.).

  Aromatic carboxylic acids include, for example, benzoic acid, o-, m- and p-chlorobenzoic acid, o-, m- and p-fluorobenzoic acid, o-, m- and p-nitrobenzoic acid, o- , M- and p-tolubenzoic acid, 2,4-dichlorobenzoic acid, p-methoxybenzoic acid, α-naphthenic acid, β-naphthenic acid and other aromatic monocarboxylic acids, phthalic acid, isophthalic acid, terephthalic acid, etc. Of the aromatic dicarboxylic acids. Aromatic carboxylic acids also include carboxylic acids having an aralkyl group such as phenylacetic acid, p-hydroxyphenylacetic acid, and p-methoxyphenylacetic acid.

  The heterocyclic carboxylic acid includes a carboxylic acid having a heterocyclic group containing a 5- or 6-membered ring containing at least one atom selected from nitrogen, oxygen and sulfur atoms as a heteroatom, such as 2-thiophenecarboxylic acid, Heterocyclic carboxylic acid having a sulfur or oxygen atom as a hetero atom such as 2-furoic acid, nicotinic acid, isonicotinic acid, pyrazine carboxylic acid, carboxylic acid having a nitrogen atom as a hetero atom, indole carboxylic acid, etc. Condensed heterocyclic carboxylic acids and the like.

  Examples of the carboxylic acid having a substituent on the aliphatic hydrocarbon group, alicyclic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group represented by R include amino acid compounds and hydroxy acid compounds. Examples of the amino acid compound include α-amino acids such as glycine, α-aminopropionic acid and α-aminobutyric acid, β-amino acids such as 3-aminopropionic acid, and the like. Examples of the hydroxy acid compound include α-hydroxy acid, β-hydroxy acid, γ-hydroxy acid and the like. The number of carbon atoms of the hydroxy acid compound is, for example, 2 to 18, preferably about 2 to 8.

[式中、R₁、R₂は、同一もしくは異種の、水素原子、または置換基を有してもよい炭化水素基を示し、R₁とR₂は隣接する炭素原子と共に環を形成していてもよい。] で表される化合物を例示することができる。 Examples of the α-hydroxy acid compound include the following formula (Ia)

[Wherein, R ₁ and R ₂ represent the same or different hydrogen atoms or optionally substituted hydrocarbon groups, and R ₁ and R ₂ form a ring together with adjacent carbon atoms. May be. The compound represented by these can be illustrated.

Examples of the substituent that R ₁ , R ₂ and R ₁ , R ₂ may have include a hydrogen atom, an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an aromatic group described in the explanation section for R above. Group hydrocarbon groups and substituents that these groups may have. For example, the alkyl group having about 1 to 12 carbon atoms, the alkenyl group having about 2 to 12 carbon atoms, the alkynyl group having about 2 to 12 carbon atoms, and the cycloalkyl group having about 3 to 10 carbon atoms described in the explanation part of R above. An aryl group having about 6 to 14 carbon atoms and an aralkyl group having about 7 to 10 carbon atoms such as phenylmethyl, 1-phenylethyl, 3-phenylpropyl and the like.
Examples of the ring in the case where R ₁ and R ₂ form a ring with adjacent carbon atoms include cyclopropyl having about 3 to 8 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl ring, etc. An alkane ring etc. can be mentioned.

  Specific examples of the α-hydroxy acid compound include glycolic acid, lactic acid, 2-hydroxyisobutyric acid, 2-hydroxybutyric acid, 2-hydroxy-4-methylbutyric acid, 2-hydroxy-2-methylbutyric acid, 2 -Hydroxy-3-methylbutyric acid, 2-hydroxy-3-butenoic acid, 2-hydroxyvaleric acid, 2-hydroxyhexanoic acid, 2-hydroxyoctanoic acid and other aliphatic α-hydroxy acids, 2-hydroxy-cyclohexanecarboxylic acid And alicyclic α-hydroxy acids such as α-hydroxycyclopentanecarboxylic acid and α-hydroxycyclohexanecarboxylic acid, and aromatic α-hydroxy acids such as mandelic acid and 2-hydroxy-3-phenylbutyric acid. .

Specific examples of the β-hydroxy acid compound include 3-hydroxypropanoic acid, 3-hydroxybutyric acid, 3-hydroxyhexanoic acid, 2-hydroxycyclohexanecarboxylic acid, and 3-hydroxy-3-phenylpropanoic acid. Can be mentioned.
Specific examples of the γ-hydroxy acid compound include 4-hydroxybutyric acid, 4-hydroxyhexanoic acid, 3-hydroxyhexanecarboxylic acid, 4-hydroxy-4-phenylbutyric acid, and the like.

  The crude carboxylic acid aqueous solution containing the carboxylic acid amide used in the present invention may be produced by any method, but usually the carboxylic acid ammonium salt aqueous solution produced by the hydrolysis reaction using a nitrile compound as a raw material is desalted. It is obtained by doing. The nitrile compounds mentioned here can be defined as the nitrile compounds corresponding to the various carboxylic acids described above. That is, the representative nitrile compound can be represented by the formula RCN. (In the formula, R is completely the same as the definition in the above-mentioned carboxylic acid RCOOH, and is omitted here.)

  A preferred nitrile compound is an α-cyanohydrin compound, for example, the following formula (Ib)

[式中、R₁、R₂は、同一もしくは異種の、水素原子、または置換基を有してもよい炭化水素基を示し、R₁とR₂は隣接する炭素原子と共に環を形成していてもよい。] で表される化合物を例示することができる。ここでのR₁、R₂の具体例についても、上記、α−ヒドロキシ酸と全く同一なので、ここでは省略する。

[Wherein, R ₁ and R ₂ represent the same or different hydrogen atoms or optionally substituted hydrocarbon groups, and R ₁ and R ₂ form a ring together with adjacent carbon atoms. May be. The compound represented by these can be illustrated. The specific examples of R ₁ and R ₂ here are the same as those of the α-hydroxy acid, and are omitted here.

  More preferable nitrile compounds are α-cyanohydrin compounds having a small number of carbon atoms such as glycolonitrile and lactonitrile.

  In the present invention, it is essential to hydrolyze the carboxylic acid amide in the crude carboxylic acid aqueous solution containing the carboxylic acid amide. Therefore, it is assumed that the crude carboxylic acid aqueous solution contains the carboxylic acid amide. It becomes. Thus, first, the reaction method in which a carboxylic acid amide is by-produced as a by-product when preparing an aqueous solution of an ammonium carboxylate salt by hydrolysis of the nitrile compound will be described with various examples.

  For example, specifically, a method of hydrolyzing a nitrile compound using a metal catalyst can be mentioned. (Patent Document 6) Since the hydrolysis reaction goes through a carboxylic acid amide that is an intermediate, the carboxylic acid amide may remain.

  As another example, a method for producing a carboxylic acid ammonium salt using a nitrile compound as a raw material and using a combination of nitrilase or nitrile hydratase and amidase can be mentioned. Here, the nitrilase is an enzyme that converts a nitrile compound directly into an ammonium carboxylate, a nitrile hydratase is an enzyme that converts a nitrile compound into a carboxylate amide, and an amidase is an enzyme that converts a carboxylate amide into an ammonium carboxylate.

  The nitrilase, nitrile hydratase, or amidase enzyme is not particularly limited except that a carboxylic acid amide is included as a by-product during the reaction, and any nitrilase, nitrile hydratase, or amidase enzyme can be used. Those derived from cells or artificially synthesized based on genetic information can be used, but those derived from microbial cells are preferably used because of the amount of enzyme expression per weight and ease of handling. . Many microbial species are known, and examples of those having high nitrilase activity include Rhodococcus genus, Pseudomonas genus, Acinetobacter genus, Alcaligenes genus, and Corynebacterium genus. Examples of nitrile hydratase and amidase having high activity include Rhodococcus genus and Pseudomonas genus. For the production of an aqueous solution of ammonium carboxylate according to the present invention, those having particularly high nitrilase activity are preferred, particularly the genus Acinetobacter which is a gram-negative bacterium, more preferably Acinetobacter sp. AK226 (FERM BP-08590). .

[Reference to Deposited Biological Material 1]
1) Name and address of the depository institution
2) National Institute of Advanced Industrial Science and Technology, Patent Organism Depositary Center 1st, 1st East, 1st Street, Tsukuba City, Ibaraki, Japan 6th (zip code 305-8566)
3) Acceptance number
FERM BP-08590

  The nitrilase may be, for example, a microorganism in which a natural or artificially improved nitrilase gene has been incorporated by a genetic engineering technique, or a nitrilase enzyme extracted from the microorganism. In order to produce a carboxylate ammonium salt using a small amount of a microorganism having a low expression level of nitrilase or a microorganism expressing a nitrilase having a low conversion activity from a nitrile compound to ammonium carboxylate, a longer reaction time is required. Therefore, it is desirable to use a microorganism that highly expresses nitrilase as much as possible, a microorganism that expresses a nitrilase having a high conversion activity, or a nitrilase enzyme extracted from the microorganism.

  As the form of the enzyme catalyst, microorganisms / animal / plant cells or the like may be used as they are, or the microorganisms / animal / plant cells themselves, or those treated by disruption, or nitrilase required from the microorganisms / animal / plant cells, etc. An enzyme extracted from the enzyme may be used as it is, or an enzyme immobilized by a general entrapment method, a crosslinking method, a carrier binding method, or the like may be used. Examples of the immobilization carrier used for immobilization include, but are not limited to, glass beads, silica gel, polyurethane, polyacrylamide, polyvinyl alcohol, carrageenan, alginic acid, and photocrosslinking resin.

  When microorganisms, animal and plant cells, etc. are used as they are, they may be suspended only in water (distilled water and / or ion-exchanged water), but they are usually suspended in a buffer solution because of osmotic pressure. The buffer in this case may be a general inorganic salt such as a phosphate buffer, but in order to reduce the contamination of impurities as much as possible, it is most preferable to use a carboxylic acid ammonium salt as a reaction product. Moreover, also when using what was fix | immobilized, it is normally suspended and used for a buffer solution from the relationship of osmotic pressure. The concentration of the buffer solution at this time is preferably as low as possible from the viewpoint of reducing impurities in the reaction solution, but is usually less than 0.1 M from the viewpoint of maintaining enzyme stability and activity, and preferably 0.01 to 0.08. M, more preferably 0.02 to 0.06M.

 As conditions for the hydrolysis reaction of the nitrile compound, the pH is preferably 6 to 8, and preferably 6.5 to 7. In particular, when the raw material is an α-cyanohydrin compound, since the α-cyanohydrin compound is a very unstable substance, it usually contains an acid component such as sulfuric acid, phosphoric acid or organic acid as a stabilizer. Therefore, it is essential to add an alkali to the reaction system in order to adjust the pH in the reaction system. In this case, the alkali used is not particularly limited as long as it does not affect the reaction, but it is desirable to use ammonia as one of the products. The form of ammonia may be a gas or ammonia water, but ammonia water is usually desirable for ease of handling.

 As for the reaction temperature for hydrolysis of the nitrile compound, if the reaction temperature is too low, the reaction activity becomes low, and more time is required for producing a high concentration carboxylic acid ammonium salt. On the other hand, if the reaction temperature is too high, the enzyme is thermally deteriorated, and if the concentration of the target ammonium carboxylate salt is high, it is difficult to reach the concentration, and as a result, treatment such as addition of a new enzyme is required. The catalyst cost becomes high. In particular, when the raw material is an α-cyanohydrin compound, if the temperature is too high, the decomposition of the substrate α-cyanohydrin compound into hydrocyanic acid and aldehydes or ketones will be promoted, resulting in reaction inhibition or deactivation. It causes a decrease in reaction activity. Therefore, the reaction temperature is usually 30 to 60 ° C, preferably 40 to 50 ° C.

  The reaction method for producing the carboxylic acid ammonium salt may be any of a fixed bed, moving bed, fluidized bed, stirring tank, etc., and may be a continuous reaction or a half-batch reaction, but in particular a non-immobilized microbial cell is used. In this case, a half-batch reaction using a stirring tank is preferable because of the ease of reaction. In that case, it is good to perform appropriate stirring from the viewpoint of reaction efficiency. In the case of carrying out a half-batch reaction, the enzyme catalyst may be used in a single batch or repeatedly. However, when the reaction is repeated, the enzyme catalyst is rapidly changed from a high concentration of ammonium carboxylate to a low concentration, so that the specific activity may be lowered due to the influence of osmotic pressure, etc., so care must be taken.

  The steady concentration of the nitrile compound as the reaction substrate is preferably 2% by weight or less, more preferably 0.1 to 1.5% by weight, still more preferably 0.1 to 1.0% by weight, and most preferably 0.2 to 0.5% by weight. Good. If the concentration of the nitrile compound is too high, the effects of product inhibition and / or deactivation, or substrate inhibition and / or deactivation that become noticeable only at a high product accumulation concentration increase rapidly, and have progressed until then. The reaction may stop. On the other hand, if the concentration of the nitrile compound is too low, the reaction rate is lowered, which is disadvantageous because the carboxylate ammonium salt cannot be produced efficiently. For the above reasons, it is very important to control the steady concentration of the nitrile compound during the reaction.

  The dry enzyme catalyst weight used for the carboxylic acid ammonium salt produced varies depending on the type of substrate and is not necessarily limited, but is usually 1/100 or less, preferably 1/100 to 1/200, more preferably 1/100. 200 to 1/300, more preferably 1/300 to 1/500. If the amount of the dry enzyme catalyst used relative to the carboxylic acid ammonium salt produced is too large, a large amount of impurities derived from the enzyme catalyst suspension is entrained in the reaction solution, which increases the purification cost and lowers the product quality. Conversely, if the amount of dry enzyme catalyst used for the carboxylic acid ammonium salt to be produced is too small, the productivity per reactor volume is lowered, and a large reactor size is required, which is economically disadvantageous.

  The carboxylic acid ammonium salt prepared by the above method is removed by filtering, centrifuging, MF treatment or the like to obtain a carboxylic acid ammonium salt aqueous solution. Furthermore, activated carbon treatment may be performed in a timely manner for the purpose of removing the coloring substance and / or coloring cause substance. The activated carbon used may be general coconut shell activated carbon, synthetic activated carbon, or the like. The amount of activated carbon used may be an amount that can reduce the coloring substance and / or coloring cause substance to the target specification.

  Moreover, even if it is the crude carboxylic acid ammonium salt aqueous solution prepared by methods other than the hydrolysis reaction of a nitrile compound, the case where carboxylic acid amide is contained as an impurity is considered. This is because the conversion reaction from carboxylic acid amide to ammonium carboxylate is an equilibrium reaction, and depending on the conditions, the conversion reaction from ammonium carboxylic acid to carboxylic acid amide may proceed very slightly depending on the reverse reaction. is there. As a method other than the hydrolysis reaction of the nitrile compound, for example, ammonia is used as a pH adjuster in the production of lactic acid and succinic acid by fermentation.

  Next, a process for producing a crude carboxylic acid aqueous solution containing a carboxylic acid amide by desalting a crude carboxylic acid ammonium salt aqueous solution containing the carboxylic acid amide will be described.

 A method for desalting a crude aqueous solution of a carboxylic acid ammonium salt containing a carboxylic acid amide is not particularly limited, and various methods can be exemplified. For example, (i) an ion exchange method and (Ii) Two electrodialysis methods will be described.

 There are roughly two methods for desalting an aqueous solution of a crude carboxylic acid ammonium salt containing a carboxylic acid amide by an ion exchange method. One is a method using a cation exchange resin, and the other is a method using an anion exchange resin. In the case of the method using the cation exchange resin, the resin to be used may be a strong acid cation exchange resin or a weak acid cation exchange resin, but a strong acid cation exchange resin is preferable. . Specifically, for example, Diaion SK1B, SK104, SK110, SK112, SK116, PK208, PK212, PK216, PK220, PK228, UBK530, UBK550, UBK535, UBK555 ( (Mitsubishi Chemical Co., Ltd.), Levacit S100, S109, SP112, STV40, MSD1368 (above LANXESS), Amberlite IR120B, 120BN, IR124, 1006F, 200CT, 252 (above organo) ), Dowex Monosphere 650C, Marathon C, HCR-S, Marathon MSC (manufactured by Dow Chemical Company) and the like, but are not necessarily limited thereto. These cation exchange resins are used after being regenerated into a proton (H +) type by a conventional method.

 As a method of using the cation exchange resin in the present invention, a usual method is adopted. That is, it may be a batch type in which a predetermined amount of a cation exchange resin is added to a crude carboxylic acid ammonium salt aqueous solution containing the carboxylic acid amide, or alternatively, the cation exchange resin is filled in a resin tower and the carboxylic acid amide is added. A column method in which the aqueous solution of the crude ammonium carboxylate salt solution is passed can also be employed. In the case of a batch system, a crude carboxylic acid aqueous solution can be obtained by collecting the supernatant after stirring for a sufficient time to reach equilibrium adsorption of ammonium ions of the ammonium carboxylate onto the cation exchange resin. . In the case of the column method, the resin passing solution until ammonium ions leak out from the column outlet is a crude carboxylic acid aqueous solution. Incidentally, the flow direction of the column method may be up-flow or down-flow.

  The amount of the cation exchange resin used is such that the total exchange capacity of the resin is equivalent to an amount equivalent to or higher than that of ammonium ions, and in order to remove ammonium ions more reliably, the resin is usually 1.2 times equivalent or higher. It is good to use. Further, in the case of the column method, in order to increase the time until resin breakthrough and resin regeneration, it is common practice to use more excess resin.

  The temperature during the resin treatment may be room temperature, but if necessary, the resin may be heated within a range in which the heat resistance of the resin is guaranteed. Usually, it is performed at 70 ° C or lower. In the case of the column method, the liquid flow rate is in the range of 1 to 20, preferably 2 to 10, in terms of space velocity [L / L-resin / Hr].

  In the case of the column method, the point where the ammonium ion is confirmed to exceed the spec in the resin passage liquid is taken as the breakthrough point, and normal washing and regeneration operations (for example, regeneration with mineral acids such as dilute hydrochloric acid and dilute sulfuric acid) are performed from there. For example, the resin can be used repeatedly.

  In the case of the method using the anion exchange resin, the resin used may be a strong basic anion exchange resin, a medium basic anion exchange resin, or a weak basic anion exchange resin. However, a weakly basic or medium basic anion exchange resin is preferable. Specifically, for example, Amberlite IRA-93 (manufactured by Organo), Diaion WA20, WA30 (manufactured by Mitsubishi Chemical Corporation), Lebatit MP64 (manufactured by LANXESS) and the like can be mentioned.

  As a method of using the anion exchange resin in the present invention, a usual method is adopted. That is, it may be a batch type in which a predetermined amount of anion exchange resin is added to an aqueous solution of a crude carboxylic acid ammonium salt containing the carboxylic acid amide, or alternatively, the anion exchange resin is packed in a resin tower and the carboxylic acid amide is added. A column method in which the aqueous solution of the crude ammonium carboxylate salt solution is passed can also be employed. In the case of the batch type, after stirring for a sufficient time to reach equilibrium adsorption of the carboxylic acid anion on the anion exchange resin, the resin is recovered and washed, and then a mineral acid (hydrochloric acid, sulfuric acid, nitric acid, etc. ), A crude carboxylic acid aqueous solution can be obtained. In the case of the column method, after leakage of carboxylic acid anions from the column outlet, a crude ammonium carboxylate aqueous solution containing a sufficient amount of carboxylic acid amide is passed through, and the outlet liquid has the same composition as the inlet liquid. By continuing the liquid flow until it becomes, the maximum amount of carboxylate anion is adsorbed on the resin. Then, after performing sufficient washing | cleaning, the said carboxylate anion is desorbed by passing mineral acid (hydrochloric acid, a sulfuric acid, nitric acid, etc.), and crude carboxylic acid aqueous solution can be obtained.

  The temperature during the resin treatment may be room temperature, but if necessary, the resin may be heated within a range in which the heat resistance of the resin is guaranteed. Usually, it is performed at 70 ° C or lower. In the case of the column method, the liquid flow rate is in the range of 1 to 20, preferably 2 to 10, in terms of space velocity [L / L-resin / Hr].

  In the case of the column method, the breakthrough point is the point where the mineral acid anion is mixed in the resin passing liquid during the desorption operation of the carboxylate anion with mineral acid, and the outlet liquid has the same composition as the inlet liquid. The resin can be used repeatedly if normal washing and regeneration operations (for example, regeneration with a strong alkali aqueous solution such as an aqueous sodium hydroxide solution or an aqueous potassium hydroxide solution) are performed from there.

 Next, there are roughly three methods for desalting the obtained aqueous solution of crude carboxylic acid ammonium salt containing carboxylic acid amide by electrodialysis. One is that in a crude ammonium carboxylate aqueous solution containing a carboxylic acid amide using a two-chamber water splitting electrodialyzer in which bipolar membranes and cation exchange membranes are alternately arranged to form an acid chamber and a base chamber. This is a method of moving ammonium ions through a cation exchange membrane, and the other is a two-chamber water-splitting electrodialysis device in which bipolar and anion exchange membranes are alternately arranged to form an acid chamber and a base chamber. Is used to move the anion exchange membrane to the carboxylate anion in the crude aqueous solution of ammonium carboxylate containing carboxylic acid amide, and the other is a bipolar membrane, a cation exchange membrane, an anion exchange membrane, Ammonium in an aqueous solution of crude carboxylic acid ammonium salt containing carboxylic acid amide using a three-chamber water-splitting electrodialyzer arranged in order and forming a raw material chamber, an acid chamber, and a base chamber ON through the cation exchange membrane is a method of moving an anion-exchange membrane in the carboxylate anion. Any of these methods may be used, but from the viewpoint of the quality and electric efficiency of the resulting crude carboxylic acid aqueous solution, a bipolar chamber and a cation exchange membrane are alternately arranged to form an acid chamber and a base chamber. A method of transferring the cation exchange membrane to ammonium ions in a crude aqueous solution of ammonium carboxylate containing carboxylic acid amide using a water splitting electrodialyzer is preferred.

 As the bipolar membrane in the present invention, a conventionally known bipolar membrane, that is, a bipolar membrane having a structure in which a cation exchange membrane and an anion exchange membrane are bonded together can be used. Specific examples include Neoceptor BP-1 (manufactured by Astom Co., Ltd.). Other examples of the cation exchange membrane include Neoceptor CMB (manufactured by Astom Co., Ltd.), and examples of the anion exchange membrane include Neoceptor AHA (manufactured by Astom Co., Ltd.).

 As an example of the electrodialysis process in the present invention, a two-chamber method comprising a bipolar membrane and a cation exchange membrane will be described. In this method, the crude carboxylic acid aqueous solution is recovered from the acid chamber, and the ammonia aqueous solution is recovered from the base chamber. FIG. 1 shows a schematic diagram of a typical mode of a water-splitting electrodialysis apparatus used in this method. That is, in FIG. 1, the water electrolysis dialysis apparatus has two types of membranes, a bipolar membrane (B) 3 and a cation exchange membrane (C) 4, arranged alternately between a positive electrode 1 and a negative electrode 2. Two chambers, a chamber 7 and a base chamber 8, are formed. The gap 5 between the bipolar membrane (B) 3 and the positive electrode 1 and the gap 6 between the bipolar membrane (B) 3 and the negative electrode 2 are filled with an electrode solution. Here, the chamber between the anion exchanger side of the bipolar membrane (B) 3 and the cation exchange membrane (C) 4 is the base chamber 8, and the cation exchanger side of the bipolar membrane (B) 3 and the cation exchange membrane (C ) The chamber between 4 is the acid chamber 7.

 In the present invention, the water-splitting electrodialysis step using the above-mentioned known water-splitting electrodialysis apparatus is provided with an external tank for the liquid supplied to each of the acid chamber 7 and the base chamber 8, and each chamber and the external tank. A method in which electrodialysis is performed while circulating a solution between the two is preferably used. By supplying a raw aqueous solution of a crude carboxylic acid ammonium salt containing a carboxylic acid amide as a raw material to the acid chamber 7 and energizing it, ammonium ions move to the base chamber 8 through the cation exchange membrane (C) 4, At this time, it combines with OH- ions generated from the bipolar membrane (B) 3 to form an aqueous ammonia solution. In the acid chamber 7, protons generated from the bipolar membrane and the carboxylic acid anion are combined to form a non-dissociable carboxylic acid, which can remain in the acid chamber 7 and be recovered. The temperature during hydrolytic electrodialysis is usually 5 to 70 ° C, preferably 20 to 50 ° C.

  Next, a process for reducing the amount of the carboxylic acid amide by bringing the crude carboxylic acid aqueous solution containing the carboxylic acid amide into contact with a solid acid catalyst will be described.

  The solid acid catalyst used in the present invention may be anything as long as it can efficiently hydrolyze the carboxylic acid amide present in the crude carboxylic acid aqueous solution without producing an undesirable by-product, For example, zeolite, strong acid cation exchange resin, heteropoly acid salt, layered metal oxide, etc. can be mentioned.

Specific examples of the zeolite include, for example, International Zeolite Association code names FAU (X, Y-type zeolite), MFI (silicalite, ZSM-5), MOR (mordenite), MAZ (omega), and BEA (beta). , FER (ferrierite), LTA (A-type zeolite), GIS (B-type zeolite) and others.

Generally, the molar ratio of SiO ₂ to Al ₂ O ₃ in the crystal structure of the zeolite is at least 5: 1 to
Although infinite, preferably the molar ratio of SiO ₂ to Al ₂ O _{3 in} the zeolite structure is in the range of 8: 1 to 200: 1, more preferably 12: 1 to 100: 1. Preferred zeolites are those having medium to large pores, generally having a diameter of more than 4 mm (angstroms). The most preferred zeolite is one having a large pore diameter exceeding, for example, 6 mm, and includes, for example, Y-type zeolite and mordenite. Suitable zeolites are commercially available from companies such as Zeolist International, which sell a wide variety and range of zeolite products.

  Examples of the strong acid cation exchange resin include a sulfonated copolymer of styrene and divinylbenzene functionalized with a sulfonic acid group. In general, the main component of the styrene / divinylbenzene copolymer is styrene, the accessory component is divinylbenzene, and styrene accounts for 75 to 98% by weight or more of the copolymer, and divinylbenzene is 2% of styrene / divinylbenzene copolymer. It occupies less than 25% by weight. Suitable commercially available strong acid cation exchange resins include, for example, Diaion SK104, SK1B, SK110, SK112, UBK08, UBK10, UBK12, PK208, PK212, PK216, PK218, PK220, PK228, etc. (Mitsubishi Chemical or its affiliated companies), Amberlite IR120B, IR124, 200CT, 252, Amberjet 1020, 1024, Amberlist 15, 16, 31, etc. (above made by Organo), Dowex 50W, etc. (Dow Chemical) Manufactured). Moreover, Nafion etc. (made by DuPont) can also be mentioned as a cation exchange resin with higher acidity.

The heteropolyacid salt is not necessarily limited, but is selected from the group consisting of, for example, a heteropolyacid cesium salt, a heteropolyacid potassium salt, a heteropolyacid rubidium salt, and a heteropolyacid ammonium salt. The heteropolyacid salt is represented by the following formula. ^{_{H + p Z + q [XY}} 12 O 40] n- H + p Z + q [X 2 Y 18 O 62] n- H + p Z + q [XY 6 O 24] n- wherein, X is H, B, C, Na, Al, Si, P, S, Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Zr, Rh, Sn, Sb, Te, I, Re, Pt, Bi, Ce, Th, U and Np are selected from the group consisting of Y, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Zr, Nb, Mo. , Tc, Rh, Cd, In, Sn, Ta, W, Re, Tl and Pb, and Z is selected from the group consisting of Ce, K, Rb and NH ₄ . N is 2 to 5, and p + q = n. In the above formula, if Y is determined, X is determined as the corresponding atom. Of these heteropolyacid salts, cesium salts and rubidium salts are preferable, and cesium salts are particularly preferable.

The heteropolyacid moiety is not necessarily limited, but is preferably selected from those represented by the following formula (H ⁺ _n ) [XY ₁₂ O ₄₀ ] ^n- . Here, X is S, P, As, Si, or Ge, and Y is independently selected from the group consisting of Mo, W, Nb, and V. n is a number that compensates for electric charge, preferably 2 to 5, more preferably 3 to 4, and still more preferably 3. More preferably, 12-tungstophosphoric acid, 12-tungstosilicic acid, 12-molybdophosphoric acid, 12-molybdosilicic acid, 12-vanadolinic acid, 12-vanadosilicic acid and 11-molybdo-1-vanadric acid are used as the heteropolyacid. More preferably, 12-tungstophosphoric acid, 12-tungstosilicic acid, 12-molybdophosphoric acid and 12-molybdosilicic acid are used, and most preferably 12-tungstophosphoric acid is used. As the heteropolyacid salt, 12-tungstophosphoric acid cesium salt is preferably used, and more preferably 12 represented by the following formula Cs _r H _3-r PW ₁₂ O ₄₀ (where r is 2 to 3). Tungstophosphoric acid cesium salt is used, most preferably Cs _2.5 H _0.5 PW ₁₂ O ₄₀ is used.

  Examples of the layered metal oxide include, but are not necessarily limited to, for example, a cation-exchangeable layered metal oxide in which polyanion nanosheets composed of a layered metal oxide layer of titanium niobate are regularly stacked with an alkali metal cation interposed therebetween. Can do.

  The method of bringing the solid acid catalyst into contact with the crude carboxylic acid aqueous solution containing the carboxylic acid amide is not particularly limited. For example, the crude ammonium carboxylate remains in a solid state or in a suspension. A so-called batch method of mixing with an aqueous salt solution or a column method in which the solid acid catalyst is packed in a packed tower or the like and contacted by passing the aqueous solution of the crude ammonium carboxylate solution through the packed tower is selected. You can also. In addition, the flow method to the column may be an up flow or a down flow.

  In the case of the batch method, an appropriate stirring operation is preferably performed in order to increase the contact efficiency between the carboxylic acid amide and the solid acid catalyst. Although the rotation speed of stirring is not particularly limited, it is usually 20 to 500 rpm, preferably 100 to 300 rpm, more preferably 150 to 250 rpm.

  The amount of the solid acid catalyst may be used as long as the amount of the carboxylic acid amide in the aqueous solution of the crude carboxylic acid can be hydrolyzed. As mentioned above, Preferably it is 2-100 equivalent, More preferably, it is about 5-30 equivalent.

  The liquid passing speed in the column method is not particularly limited as long as it is not more than a speed at which the reduction of the target carboxylic acid amide can be sufficiently achieved. Usually, the space velocity [L / L-resin / Hr] is 0.5 to 20, preferably 1-10.

  The pressure when the solid acid catalyst is brought into contact with the crude carboxylic acid aqueous solution containing the carboxylic acid amide and the carboxylic acid amide is reduced by the hydrolysis reaction is not particularly limited, and may be under reduced pressure or under pressure. However, it is usually performed under atmospheric pressure.

  If the temperature at which the carboxylic acid amide is reduced by the hydrolysis reaction is too low, the hydrolysis reaction rate decreases, so it may not take time to obtain a certain hydrolysis reaction conversion rate, and if it is too high, It is not good because the deterioration of the functional group possessed by the solid acid catalyst becomes severe. The temperature of the hydrolysis reaction is usually 30 to 150 ° C, preferably 50 to 120 ° C, more preferably 80 to 100 ° C.

A lower pH is desirable when the carboxylic acid amide is reduced by a hydrolysis reaction. For example, in the case of a crude carboxylic acid aqueous solution containing a carboxylic acid amide obtained by desalting, if the desalting is sufficiently performed, the pH of the aqueous carboxylic acid solution approaches, and the pH becomes low. The hydrogen ion (H ⁺ ) derived from the carboxylic acid also has the ability to hydrolyze the carboxylic acid amide. By increasing the temperature, hydrolysis of the carboxylic acid amide can be performed without using the solid acid catalyst. Progress. However, such non-catalytic hydrolysis does not have a sufficient rate, and the hydrolysis rate can be increased by using the solid acid catalyst.

Some of the solid acid catalysts may or may not need to be regenerated to a hydrogen ion type (H ⁺ ) with a mineral acid or the like before the hydrolysis reaction of the carboxylic acid amide. Since the crude carboxylic acid aqueous solution containing the carboxylic acid amide contains hydrogen ions (H ⁺ ) derived from the carboxylic acid, the hydrolysis reaction of the carboxylic acid amide and the regeneration of the solid acid catalyst are performed simultaneously. Is possible. In other words, depending on conditions, the solid acid catalyst can increase the rotational speed catalytically without so-called consumption. As a condition in that case, it is easily analogized that there is a restriction that fresh hydrogen ions (H ⁺ ) are always supplied.

  The concentration of the crude carboxylic acid aqueous solution is not particularly limited, but if it is too low, the productivity will be low, and if it is too high, adverse effects such as precipitation will occur. In consideration of the limitation of the aqueous carboxylic acid ammonium salt synthesis step in the previous step, the amount is usually 5 to 80% by weight, preferably 10 to 60% by weight, and more preferably 20 to 50% by weight.

  In the conversion by the hydrolysis reaction of the carboxylic acid amide, the higher the quality, the better the quality of the final product carboxylic acid may be. However, in order to increase the conversion rate of the hydrolysis reaction of the carboxylic acid amide, the solid acid catalyst There are adverse effects such as a large amount used, high temperature conditions are required, and the hydrolysis reaction time is prolonged. In addition, the α-hydroxy acid aqueous solution obtained by bringing a crude α-hydroxy acid aqueous solution containing a trace amount of α-hydroxy acid amide into contact with the solid acid catalyst is completely removed even when it is subjected to a purification step such as ion exchange. When the poly α-hydroxy acid is finally produced, it may remain in the raw material α-hydroxy acid aqueous solution. Accordingly, the amount of α-hydroxy acid amide remaining in the α-hydroxy acid aqueous solution varies depending on the conversion rate of hydrolysis reaction of the α-hydroxy acid amide, and the α-hydroxy acid amide produces poly α-hydroxy acid. There are various adverse effects. For example, in the α-hydroxy acid oligomerization step, thermal decomposition of the remaining α-hydroxy acid amide may occur, and coloring due to the generated ammonia may occur. Furthermore, also in the cyclic dimer ester synthesis step by depolymerization of the α-hydroxy acid oligomer in the next step, the impurity N component due to the ammonia may be mixed into the cyclic dimer ester. Furthermore, in the poly α-hydroxy acid synthesis step by ring-opening polymerization of the cyclic dimer ester, there may be a case where coloring due to the impurity N content or a decrease in polymer physical properties is caused. The amount of residual carboxylic acid amide when the aqueous solution of ammonium carboxylate containing carboxylic acid amide is brought into contact with a solid acid catalyst to reduce the amount of the carboxylic acid amide is not necessarily limited, but usually 500 [weight ppm / carboxylic acid] or less Preferably, it is 300 [weight ppm / carboxylic acid] or less, more preferably 100 [weight ppm / carboxylic acid] or less, and most preferably 10 [weight ppm / carboxylic acid].

  By the way, when the solid acid catalyst is a strongly acidic cation exchange resin, the hydrolysis reaction of the carboxylic acid amide by the solid acid catalyst and the desalting of the crude ammonium carboxylate aqueous solution containing the carboxylic acid amide are simultaneously performed. Is possible. That is, in the desalting in the column method using the strong acid cation exchange resin described in the explanation of the desalting method, a crude carboxylic acid aqueous solution containing a carboxylic acid amide is generated during the operation. By contacting the strongly acidic cation exchange resin, the hydrolysis reaction of the carboxylic acid amide proceeds. However, in this case, the flow rate, temperature conditions, residence time, etc. of the crude ammonium carboxylate solution containing the carboxylate amide to the strongly acidic cation exchange resin are the conditions under which the hydrolysis reaction of the carboxylate amide proceeds sufficiently. (Determined from the rate-determining stage). The liquid flow rate is in the range of 0.1 to 5, preferably 0.5 to 2, in terms of space velocity [L / L-resin / Hr], and the temperature is usually 30 to 150 ° C, preferably 50 to 120 ° C, more preferably. The residence time varies depending on the temperature conditions and the acidity of the ion exchange resin used, but is usually 30 minutes or longer, preferably 1 hour or longer.

  According to the carboxylic acid production method of the present invention, the carboxylic acid can be obtained as an aqueous solution, and the carboxylic acid aqueous solution contains various impurities. For example, when the desalting method is ion exchange, ammonium ions partially leaked by cation exchange, anion components that are not adsorbed at all, neutral components, etc. are contained as impurities, and metal cations that have not been washed by anion exchange, Ammonium ions, neutral components and anionic components that exhibit the same behavior as carboxylic acids are included as impurities. On the other hand, when the desalting method is electrodialysis, it is difficult to achieve a desalting rate of 100%, and an anion component or the like that partially contains ammonium ions and exhibits the same behavior as carboxylic acid is contained as an impurity.

  Cationic impurities such as metal cations and ammonium ions in the solution can be purified and removed by a general cation exchange method. In addition, when the carboxylic acid to be produced is an α-hydroxy acid, which is a hydrolysis reaction product of an α-cyanohydrin compound, neutral amino acids may be by-produced as a by-product. In that case, in a high concentration α-hydroxy acid aqueous solution, the equilibrium state of the amino acids is biased toward a cationic one, which can be purified and removed by the cation exchange. Also, anionic impurities such as sulfate anions can be purified and removed by a general anion exchange method. When the solid acid catalyst is a strongly acidic cation exchange resin, hydrolysis reaction of the carboxylic acid amide by the solid acid catalyst, demineralization of a crude ammonium carboxylate aqueous solution containing the carboxylic acid amide, and the cationic property Impurities can be purified and removed at the same time.

 In particular, when the carboxylic acid produced in the present invention is an α-hydroxy acid, if the α-hydroxy acid aqueous solution obtained contains a large amount of ammonium ions, metal cations, and impurity anion components, the cyclic in the next step In order to perform the dimer ester synthesis reaction by repeating the batch reaction, it is necessary to reduce the concentration to an appropriate level in order to avoid the influence of accumulation of these cations and anions. In addition, ammonium ions cause coloration and adversely affect the physical properties of the product polymer. Therefore, it is desirable to reduce as much as possible.

  The present invention also includes a step of synthesizing an α-hydroxy acid oligomer from the α-hydroxy acid aqueous solution obtained by the above-described method for producing an α-hydroxy acid according to the present invention, and depolymerizing the α-hydroxy acid oligomer. A process for obtaining a cyclic α-hydroxy acid, and a step for ring-opening polymerization of the cyclic dimer ester to obtain a poly α-hydroxy acid.

  Hereinafter, as an example of an α-hydroxy acid, a case of glycolic acid will be taken up and a production method until polymer synthesis will be described, but the α-hydroxy acid is not limited thereto.

 In the step of synthesizing the glycolic acid oligomer, the raw material glycolic acid is heated to a temperature of usually 100 to 250 ° C., preferably 140 to 230 ° C. under reduced pressure or increased pressure in the presence of a dehydration condensation catalyst, if necessary. The condensation reaction is carried out until the distillation is virtually eliminated. After completion of the condensation reaction, the produced glycolic acid oligomer can be used as it is as a raw material for the next step. Further, the obtained glycolic acid oligomer can be taken out from the reaction system and washed with a non-aqueous solvent such as benzene or toluene to remove unreacted substances, low polymer or catalyst, and then used. The glycolic acid oligomer may be cyclic or linear. The degree of polymerization is not particularly limited, but the melting point (Tm) is usually 140 ° C. or higher, preferably 160 ° C. or higher, more preferably 180 ° C. or higher from the viewpoint of glycolide yield when performing the depolymerization reaction. It is desirable. Here, Tm is a melting point detected by using a differential scanning calorimeter (DSC) to raise the temperature at a rate of 10 ° C./min in an inert gas atmosphere.

  In the step of depolymerizing the glycolic acid oligomer to obtain glycolide, the depolymerization method is not particularly limited, and a general melt depolymerization method or solid phase depolymerization method can be employed. In this case, the depolymerization reaction system is roughly divided into two systems, a system consisting essentially of glycolic acid oligomers and a system containing glycolic acid oligomers and a polar organic solvent, corresponding to the depolymerization method employed. . When a depolymerization reaction system consisting essentially of glycolic acid oligomers is heated under normal pressure or reduced pressure, glycolide produced by the depolymerization reaction sublimates or evaporates. Therefore, glycolide can be obtained by discharging the glycolide out of the depolymerization reaction system by a method such as blowing an inert gas. Moreover, when the depolymerization reaction system which consists of a mixture containing a glycolic acid oligomer and a polar organic solvent is heated, glycolide produced | generated by the depolymerization reaction co-distills with a polar organic solvent. By separating glycolide from the distillate by a method such as crystallization, glycolide can be recovered. Also in this case, the depolymerization reaction is carried out by heating the depolymerization reaction system under normal pressure or reduced pressure. As the depolymerization method, a solution depolymerization method in which the glycolic acid oligomer is depolymerized in a solution phase is preferable from the viewpoint of preventing heavy polymerization of the glycolic acid oligomer used as a raw material and the production efficiency of glycolide.

  Furthermore, the glycolide obtained by this invention can be made into polyglycolic acid by a ring-opening polymerization method. The ring-opening polymerization is usually performed at a temperature of 100 ° C. or higher in the presence of a catalyst, and preferably about 160 to 180 ° C. The catalyst is not particularly limited as long as it is used as a ring-opening polymerization catalyst for various cyclic esters, but specific examples include, for example, tin (Sn), titanium (Ti), aluminum (Al ), Antimony (Sb), zirconium (Zr), zinc (Zn) and other metal compound oxides, halides, carboxylates, alkoxides, and the like. In general, the amount of the catalyst used may be small relative to the cyclic ester, based on the cyclic ester. Usually, it may be within the range of 0.0001 to 0.5% by weight, preferably 0.001 to 0.1% by weight.

  In a typical process of the present invention, a typical example of a process combining a hydrolysis reaction step, a desalting step (electrodialysis) using an nitrile compound as a raw material, an amide decomposition step, a cation exchange purification step, and an anion exchange purification step Fig. 2 is a schematic diagram of (Process A). Hydrolysis reaction step using nitrile compound as raw material, desalting step (electrodialysis), step having both amidolysis and cation exchange purification (α cation exchange step), anion exchange A typical example of a process combining purification steps (Process B) is shown in the schematic diagram of FIG. 3, a hydrolysis reaction step using a nitrile compound as a raw material, a step that combines desalting, amide decomposition, and cation exchange purification (β cation) 4) A representative example of a process combining the anion exchange step) and the anion exchange step (process C) is shown in the schematic diagram of FIG. The actual operation will be specifically described based on these.

Process A
In the example of FIG. 2, in the hydrolysis reaction step <1>, the reactor is charged with a nitrilase enzyme catalyst (microbial cell) and water, the nitrile compound is supplied from the nitrile compound supply line 1, and at a predetermined temperature and a predetermined pH. The hydrolysis reaction is carried out while keeping the constant nitrile compound concentration in the reaction solution constant. (Semi-batch reaction) If necessary, a pH adjuster is supplied to control the pH of the reaction solution to the optimum pH of the nitrilase to be used. When the target ammonium carboxylate concentration is reached, the supply of the nitrile compound is stopped and the reaction is continued until the unreacted nitrile compound is completely consumed. The finally obtained aqueous solution of crude carboxylic acid ammonium salt containing carboxylic acid amide was sterilized and deproteinized by purification means such as centrifugation, MF, UF, etc., through the hydrolysis reaction mixture supply line 2, Supply to the raw material chamber (acid chamber) of electrodialysis step <2>.

  In the example of FIG. 2, in the electrodialysis step <2>, a crude carboxylic acid ammonium salt aqueous solution containing a carboxylic acid amide supplied to the raw material chamber (acid chamber) is used using a bipolar electrodialysis apparatus as shown in FIG. Electrodialysis is performed to recover the crude carboxylic acid aqueous solution from the acid chamber and the ammonia aqueous solution from the base chamber. The recovered aqueous ammonia solution is recovered through the electrodialysis process base chamber ammonia mixture recovery line 4, most of it is recovered through the electrodialysis process base chamber ammonia mixture separation recovery line 6, and part of the electrodialysis process base chamber ammonia mixture is mixed. Recirculate through the liquid circulation line 5 to the electrodialyzer base chamber. On the other hand, the recovered crude carboxylic acid aqueous solution is supplied to the amidolysis reaction step <3> through the electrodialysis step acid chamber carboxylic acid mixed solution supply line 3.

  In the example of FIG. 2, in the amide decomposition reaction step <3>, the carboxylic acid amide in the crude carboxylic acid aqueous solution containing the carboxylic acid amide supplied to the packed column packed with the solid acid catalyst is hydrolyzed to obtain the target amount. A crude carboxylic acid aqueous solution in which the carboxylic acid amide is reduced is obtained below, and supplied to the anion exchange purification step <4> through the carboxylic acid mixed solution supply line 7 after the amide decomposition reaction. Incidentally, when the solid acid catalyst is a strong acid cation exchange resin, ammonium ions generated by hydrolysis of the carboxylic acid amide are adsorbed and accumulated on the strong acid cation exchange resin in the packed column, and eventually the strong acid cation exchange resin is used. When the ion exchange capacity of the ion exchange resin is exceeded, ammonia leaks from the packed tower outlet. However, although the hydrolysis reaction rate decreases, the hydrolysis activity of the carboxylic acid amide itself is maintained, so by selecting appropriate conditions, the amidolysis reaction can be continued without any special regeneration treatment. Is possible.

  In the example of FIG. 2, in the anion exchange purification step <4>, the anion component in the crude carboxylic acid aqueous solution can be purified and removed by anion exchange. Incidentally, the anion exchange resin to be used is prepared in OH type in advance, and immediately after passing the crude carboxylic acid aqueous solution, the adsorption of the carboxylic acid anion proceeds to the ion exchange site. It is replaced with a high anion component (for example, sulfate anion), and the outlet liquid becomes a purified carboxylic acid aqueous solution, and is supplied to the cation exchange purification step <5> through the carboxylic acid mixed solution supply line 8 after the anion exchange purification step. . The resin that has passed through is subjected to washing, reverse regeneration, washing, regeneration, and washing, and the washing solution / regeneration solution is collected through the anion exchange purification process washing solution and the regeneration / reverse regeneration solution collection line 9.

  In the example of FIG. 2, in the cation exchange purification step <5>, the cation component in the aqueous carboxylic acid solution can be purified and removed by cation exchange after the anion exchange purification step. Incidentally, the cation exchange resin to be used is prepared in advance in the H type and replaced with a cation component having a high adsorption selectivity coefficient (for example, ammonium ion, metal cation, etc.), and the outlet liquid is a carboxylic acid aqueous solution obtained by purifying the cation component, After the cation exchange purification step, it is recovered through the carboxylic acid mixture recovery line 10. The resin that has passed through is subjected to washing, reverse regeneration, washing, regeneration, and washing, and the washing solution / regeneration solution is collected through the cation exchange purification process washing solution and the regeneration / reverse regeneration solution collection line 11.

Process B
In the example of FIG. 3, in the hydrolysis reaction step <1>, the reactor is charged with a nitrilase enzyme catalyst (microbial cell) and water, the nitrile compound is supplied from the nitrile compound supply line 1, and at a predetermined temperature and a predetermined pH. The hydrolysis reaction is carried out while keeping the constant nitrile compound concentration in the reaction solution constant. (Semi-batch reaction) If necessary, a pH adjuster is supplied to control the pH of the reaction solution to the optimum pH of the nitrilase to be used. When the target ammonium carboxylate concentration is reached, the supply of the nitrile compound is stopped and the reaction is continued until the unreacted nitrile compound is completely consumed. The finally obtained aqueous solution of crude carboxylic acid ammonium salt containing carboxylic acid amide was sterilized and deproteinized by purification means such as centrifugation, MF, UF, etc., through the hydrolysis reaction mixture supply line 2, Supply to the raw material chamber (acid chamber) of electrodialysis step <2>.

  In the example of FIG. 3, in the electrodialysis step <2>, a crude carboxylic acid ammonium salt aqueous solution containing a carboxylic acid amide supplied to the raw material chamber (acid chamber) is used using a bipolar electrodialysis apparatus as shown in FIG. Electrodialysis is performed to recover the crude carboxylic acid aqueous solution from the acid chamber and the ammonia aqueous solution from the base chamber. The recovered aqueous ammonia solution is recovered through the electrodialysis process base chamber ammonia mixture recovery line 4, most of it is recovered through the electrodialysis process base chamber ammonia mixture separation recovery line 6, and part of the electrodialysis process base chamber ammonia mixture is mixed. Recirculate through the liquid circulation line 5 to the electrodialyzer base chamber. On the other hand, the recovered crude carboxylic acid aqueous solution is supplied to the α cation exchange step <6> through the electrodialysis step acid chamber carboxylic acid mixed solution supply line 3.

  In the example of FIG. 3, in the α cation exchange step <6>, the carboxylic acid amide in the crude carboxylic acid aqueous solution containing the carboxylic acid amide supplied to the packed column packed with the strongly acidic cation exchange resin is hydrolyzed. In addition to obtaining a crude aqueous carboxylic acid solution with a reduced amount of carboxylic acid amide below the target amount, the produced ammonium ion was purified and removed by cation exchange with the strong acid cation exchange resin, and the α-cation exchanged carboxylic acid The acid mixture supply line 12 is supplied to the anion exchange purification step <4>. The strongly acidic cation exchange resin to be used is prepared in the H form in advance, and the resin that has passed through is washed, reverse regenerated, washed, regenerated, washed, and the washing solution / regenerated solution is the washing solution after α cation exchange. And it collects through the regeneration / reverse regeneration solution recovery line 13.

  In the example of FIG. 3, in the anion exchange purification step <4>, the anion component in the crude carboxylic acid aqueous solution can be purified and removed by anion exchange. Incidentally, the anion exchange resin to be used is prepared in OH type in advance, and immediately after passing the crude carboxylic acid aqueous solution, the adsorption of the carboxylic acid anion proceeds to the ion exchange site. It is replaced with a high anion component (for example, sulfate anion), and the outlet liquid becomes a carboxylic acid aqueous solution in which the anion component is purified, and is recovered through the carboxylic acid mixed liquid recovery line 14 after the anion exchange purification step. The resin that has passed through is subjected to washing, reverse regeneration, washing, regeneration, and washing, and the washing solution / regeneration solution is collected through the anion exchange purification step washing solution and the regeneration / reverse regeneration solution collection line 15.

Process C
In the example of FIG. 4, in the hydrolysis reaction step <1>, the reactor is charged with a nitrilase enzyme catalyst (microbial cell) and water, and the nitrile compound is supplied from the nitrile compound supply line 1, at a predetermined temperature and a predetermined pH. The hydrolysis reaction is carried out while keeping the constant nitrile compound concentration in the reaction solution constant. (Semi-batch reaction) If necessary, a pH adjuster is supplied to control the pH of the reaction solution to the optimum pH of the nitrilase to be used. When the target ammonium carboxylate concentration is reached, the supply of the nitrile compound is stopped and the reaction is continued until the unreacted nitrile compound is completely consumed. The finally obtained aqueous solution of crude carboxylic acid ammonium salt containing carboxylic acid amide was sterilized and deproteinized by purification means such as centrifugation, MF, UF, etc., through the hydrolysis reaction mixture supply line 2, Feed to β cation exchange step <7>.

  In the example of FIG. 4, in the β cation exchange step <7>, cation exchange is performed on ammonium ions in a crude ammonium carboxylate aqueous solution containing a carboxylic acid amide supplied to a packed column packed with a strongly acidic cation exchange resin. The carboxylic acid amide is hydrolyzed at the same time as adsorbing to the strong acid cation exchange resin to obtain a crude carboxylic acid aqueous solution in which the carboxylic acid amide is reduced below the target amount, and the carboxylic acid mixed solution after β cation exchange The feed line 16 is supplied to the anion exchange purification step <4>. The strongly acidic cation exchange resin to be used is prepared in the H type in advance, and the resin that has passed through is washed, reverse regenerated, washed, regenerated, washed, and the washing solution / regenerated solution is the washing solution after β cation exchange. And it collects through the regeneration / reverse regeneration solution recovery line 17.

  In the example of FIG. 4, in the anion exchange purification step <4>, the anion component in the crude carboxylic acid aqueous solution can be purified and removed by anion exchange. Incidentally, the anion exchange resin to be used is prepared in OH type in advance, and immediately after passing the crude carboxylic acid aqueous solution, the adsorption of the carboxylic acid anion proceeds to the ion exchange site. It is replaced with a high anion component (for example, sulfate anion), and the outlet liquid becomes a carboxylic acid aqueous solution in which the anion component is purified, and is recovered through the carboxylic acid mixed liquid recovery line 18 after the anion exchange purification step. The resin that has passed through is subjected to washing, reverse regeneration, washing, regeneration, and washing, and the washing solution / regeneration solution is collected through the anion exchange purification step washing solution and the regeneration / reverse regeneration solution collection line 19.

Hereinafter, the present invention will be described in more detail with reference to examples. In addition, this invention is not necessarily limited by these Examples, A various change and modification are possible unless it exceeds the summary. In particular, in Examples, only experiments using glycolonitrile (HO—CH ₂ —CN), a crude ammonium glycolate aqueous solution containing glycolamide, and a crude glycolic acid aqueous solution containing glycolamide are shown. Considering that it is important that the carboxylic acid amide present in the reaction solution can be reduced using a solid acid catalyst, α-hydroxynitrile other than glycolonitrile, a crude α-hydroxy acid ammonium salt containing α-hydroxyacid amide The same phenomenon occurs not only in the aqueous solution and the crude α-hydroxy acid aqueous solution containing the α-hydroxy acid amide, but also in other nitrile compounds, the aqueous solution of the crude carboxylic acid ammonium salt containing the carboxylic acid amide, and the crude carboxylic acid aqueous solution containing the carboxylic acid amide. It can be easily inferred that the results are obtained.

  Acinetobacter sp. AK226, which is a biocatalyst used in the present invention, was internationally deposited by the present inventors at the Patent Organism Depositary, National Institute of Advanced Industrial Science and Technology, and has an international deposit number of FERM BP-08590. Is.

  The method for measuring the weight of the dried biocatalyst in the biocatalyst suspension was performed as follows. First, an appropriate amount of a biocatalyst suspension having an appropriate concentration was taken, cooled to −80 ° C., completely dried using a freeze dryer, and the concentration of the biocatalyst suspension was calculated from the weight value. For the immobilized product, the dry biocatalyst weight was calculated from the amount of the biocatalyst suspension that was known at the time of immobilization and the amount of the crosslinking agent and the immobilized carrier.

  Analysis of the hydrolysis and amidolysis reaction liquid and various treatment liquids was performed as follows. The substrate glycolonitrile, the product glycolic acid or ammonium glycolate, and the byproduct glycolamide were measured by high performance liquid chromatography. The column is an ion exclusion column (Shimadzu Shim-pack SCR-101H), the column temperature is 40 ° C, the mobile phase is phosphoric acid aqueous solution (pH = 2.3), the flow rate is 0.7 mL / min, and the detector is UV (Shimadzu SPD-10AV vp 210 nm) and RI (Shimadzu RID-6A), the injection volume was 10 μL.

  The analysis of the depolymerization reaction solution was performed by gas chromatography. Detector is FID, column is medium polarity capillary column (DB-1701 made by J & W SCIENTIFIC, length: 60m, inner diameter: 0.25mm, film thickness: 1μm), carrier: helium (300kPa), injection temperature: 200 ° C, detector temperature : 200 ° C., operating temperature: 100 ° C. × 5 minutes, 20 ° C./minute, 270 ° C. × 10 minutes.

  Here, the glycolamide concentration in the amidolysis reaction experiment is calculated by the following procedure. In the deamidation reaction experiment, the raw material and the sample liquid sampled at a predetermined time are diluted with distilled water to a predetermined concentration, and the glycolamide and glycolic acid concentrations are calculated by the high performance liquid chromatography. A value obtained by dividing the glycolamide concentration by the glycolic acid concentration is the glycolamide concentration [weight ppm / glycolic acid], and is calculated by (Equation 1). The amidolysis rate is a value obtained by dividing the raw material glycoloamide concentration by the sample glycoloamide concentration by the raw material glycoloamide concentration, and is calculated by (Equation 2).

・ Glycolamide concentration [ppm by weight / glycolic acid] = glycolamide concentration [wt%] / glycolic acid concentration [wt%] × 1000000 (Formula 1)
・ Degradation rate of amido [%] = glycolamide concentration of raw material [wt%] ÷ glycolamide concentration of sample [wt%] × 100 (Formula 2)

[Reference Example 1] Preparation of microbial cell catalyst 0.1% by weight of sodium chloride, 0.1% by weight of potassium dihydrogen phosphate, 0.05% by weight of magnesium sulfate heptahydrate, 0.005% by weight of ferrous sulfate heptahydrate, 0.1% of ammonium sulfate 250% of the culture solution containing 0.005% by weight of 0.1% by weight, potassium nitrate 0.1% by weight potassium nitrate in a conical flask, adjusted with sodium hydroxide so that the pH is 7, and sterilized at 121 ° C for 20 minutes, Acetonitrile 0.5 wt% was added. This was inoculated with Acinetobacter sp. AK226 and cultured with shaking at 30 ° C. (preculture). Mist powder 0.3% by weight, sodium glutamate 0.5% by weight, ammonium sulfate 0.5% by weight, dipotassium hydrogen phosphate 0.2% by weight, potassium dihydrogen phosphate 0.15% by weight, sodium chloride 0.1% by weight, magnesium sulfate heptahydrate 0.18% by weight %, Manganese chloride tetrahydrate 0.02%, calcium chloride dihydrate 0.01%, iron sulfate heptahydrate 0.003%, zinc sulfate heptahydrate 0.002%, copper sulfate pentahydrate 0.002% A 5 L jar fermenter was charged with 3 L of a broth containing 2% by weight and 2% soybean oil, sterilized at 121 ° C. for 20 minutes, inoculated with the pre-culture solution, and aerated and stirred at 30 ° C. Soybean oil feed was started 10 hours after the start of the culture. The pH was controlled with phosphoric acid and aqueous ammonia so that the pH was 7, and finally a suspension of about 5% by weight of Acinetobacter sp. AK226 was obtained. Furthermore, it was washed twice with 0.06M phosphate buffer, and finally Acinetobacter sp. AK226 suspension (dry cell concentration 10.8 wt%) suspended in phosphate buffer was obtained.

[Reference Example 2] Preparation of glycolonitrile for hydrolysis reaction raw material Glycolonitrile for hydrolysis reaction raw material was prepared by using 37 wt% formalin and hydrocyanic acid gas manufactured by Mitsubishi Gas Chemical Co., Ltd., with sodium hydroxide as the catalyst, pH = 4 Cyanhydrination reaction was carried out at a reaction temperature of 40 ° C. After adjusting to pH = 2.2 using sulfuric acid, stripping is performed at 50 ° C under reduced pressure (final ultimate pressure: 50 mmHg) for the purpose of methanol removal, and distilled water is added only for the concentration accompanying water evaporation. Finally, an aqueous solution (pH = 2.0) of glycolonitrile: 55.3% by weight was obtained. This glycolonitrile aqueous solution was used as a raw material for the hydrolysis reaction using a biocatalyst in the following examples.

[Reference Example 3] Preparation 1 of glycolic acid aqueous solution for amidolysis reaction raw material 1
The simulated glycolic acid aqueous solution for the amide decomposition reaction raw material was prepared using DuPont Gripure (glycolic acid crystal), Aldrich Glycolamide, and distilled water.

[Reference Example 4] Preparation 2 of glycolic acid aqueous solution for amidolysis reaction raw material 2
A 5 L four-necked flask is charged with 24 g of 10.8 wt% Acinetobacter sp. AK226 suspension prepared in Reference Example 1 above and 1100 g of distilled water, and a pH meter and a thermometer are installed in the flask, and the pH and temperature of the reaction solution are set. The mixture was placed in a 50 ° C constant temperature water bath and stirred with a three-one motor, and kept for a while until the internal temperature reached 50 ° C. Next, a 55.3 wt% glycolonitrile aqueous solution (pH = 2.0) prepared by the procedure of Reference Example 2 was fed at 0.5 g / min using a liquid chromatography pump. In order to neutralize sulfuric acid contained as a stabilizer in the raw material glycolonitrile, 1.5 wt% aqueous ammonia was fed by a tube pump. The ammonia water feed pump was set so that the pH of the internal solution was 6.9 ± 0.1 by control with a pH meter. Sampling was periodically performed during the reaction, and the concentrations of glycolonitrile and ammonium glycolate were measured by high performance liquid chromatography, and the amount of raw material added was adjusted so that the steady glycolonitrile concentration was 2% by weight or less. The final ammonium glycolate accumulation concentration was 41.4% by weight, and the substrate glycolonitrile was not detected. Next, the resulting glycolic acid ammonium salt aqueous solution was treated at a rotational speed of 10,000 pm, a treatment time of 20 min, and a treatment temperature of 4 ° C. using a centrifuge (manufactured by Kubota: high-speed centrifuge 7700), and the supernatant was recovered. Thereafter, the resultant was treated with UF (Asahi Kasei Chemicals Corp .: SIP-0013) at a flow rate of 1 ml / min and a treatment temperature of 40 ° C. to obtain a 37.2 wt% aqueous ammonium glycolate salt solution. Since this liquid was slightly colored, 5g of commercial activated carbon (Shirakaba A: manufactured by Nippon Enviro Chemicals) was added and stirred at room temperature for 45 minutes, and then the treatment liquid was collected by decantation to remove the colored components. . The ammonium glycolate concentration was 40.5% by weight, and the by-product glycolamide concentration was 0.24% by weight. Next, this solution is electrodialyzed using a bipolar electrodialysis apparatus (ACYLYZER EX3B manufactured by Astom Co., Ltd.) with a combination of a bipolar membrane (Astom Neoceptor BP-1) and a cation exchange membrane (Astom Neoceptor CMB). The crude glycolic acid aqueous solution was obtained. The composition was a glycolic acid concentration of 30.2% by weight and a glycolamide concentration of 6700 [weight ppm / glycolic acid].

[Examples 1 to 3]
A 100 mL three-necked flask was charged with 50 g of a glycoloamide-containing glycolic acid aqueous solution prepared by the method of Reference Example 3 above and a strongly acidic cation exchange resin manufactured by Organo Co., Ltd. (Amberlite IR120B Na previously regenerated to H type). Under the conditions, glycoloamide decomposition experiment was conducted. The results of changes over time in the amide decomposition rate are shown in Table 1 and FIG.

[Comparative Examples 1 and 2]
A glycolamide decomposition experiment (Comparative Example 1) was performed under the same conditions as in Example 1 except that no strongly acidic cation exchange resin was used. Further, a glycolamide decomposition experiment (Comparative Example 2) was performed under the same conditions as in Comparative Example 1 except that the glycolic acid concentration was changed to 70% by weight. The results are shown in Table 1 and FIG.

[Example 4]
A glycolamide decomposition experiment was performed under the same conditions as in Example 1 except that the strongly acidic cation exchange resin was changed to Nafion NR50 manufactured by DuPont. The results are shown in Table 1 and FIG.

[Comparative Example 3]
The glycolamide decomposition experiment was performed under the same conditions as in Example 2 except that no strongly acidic cation exchange resin was used. The results are shown in Table 1 and FIG.

[Example 5]
An amide hydrolysis reaction experiment (100 ° C. × 30 min) was carried out in the same manner as in Example 2 except that 10 wt% aqueous ammonia was added so that the molar ratio of ammonia to the total resin exchange capacity was 1.05 times. As a result, the amide decomposition rate was 43%.

[Comparative Example 4]
A glycolamide decomposing experiment (100 ° C. × 30 min) was carried out under the same conditions as in Example 5 except that no strongly acidic cation exchange resin was used. As a result, the amidolysis rate was less than 1%.

[Example 6]
Zeolyst's zeolite ZSM-5 (ZeolystCBV3024E) was prepared according to a general method in advance to be H-shaped and calcined in 3 g and the glycolamide containing glycolic acid aqueous solution prepared in Reference Example 3 (GA: 30 wt%, GAM: 12000 wt) -ppm / GA) 50 g was charged in a 100 mL three-necked flask and subjected to a glycolamide decomposition experiment (100 ° C. × 2 Hr). The amide decomposition rate was 92%.

[Example 7]
A glycolamide decomposition experiment was conducted in the same manner as in Example 6 except that a heteropolyacid salt and Cs _2.5 H _0.5 PW ₁₂ O ₄₀ were used instead of zeolite, and the amide decomposition ratio was 88%.

[Examples 8 to 13]
A glass column (12φ x 300 mmH) is charged with 35 mL of Organo's strongly acidic cation exchange resin, Amberlite IR120B Na (total exchange capacity is 70 meq), and 400 mL of 2N hydrochloric acid is passed at SV (empty speed) = 4. Then, it was regenerated and washed thoroughly with distilled water. Next, the crude glycolic acid aqueous solution prepared in Reference Example 4 was passed through the regenerated strong acidic cation exchange resin, and the recovered liquid from the column outlet was analyzed to evaluate the amide decomposition rate under each condition. The amide decomposition rate under each condition is expressed as the average value of the analysis value of the outlet recovered liquid when the liquid flow rate is 1 time, 1.5 times, and 2 times the resin volume used, and the results are shown in Table 2. .

[Examples 14 to 17]
Before passing the crude glycolic acid aqueous solution prepared in Reference Example 4 through the regenerated strong acidic cation exchange resin, 400 mL of 2N ammonia water was passed at SV (superficial velocity) = 4 to A glycolamide decomposing reaction experiment was conducted in the same manner as in Example 8, except that the cation exchange resin was converted to NH ₄ type and washed thoroughly with distilled water. The results are shown in Table 3.

[Example 18]
A glass column (12φ x 300 mmH) is charged with 35 mL of Organo's strongly acidic cation exchange resin, Amberlite IR120B Na (total exchange capacity is 70 meq), and 400 mL of 2N hydrochloric acid is passed at SV (empty speed) = 4. Then, it was regenerated and washed thoroughly with distilled water. Next, 25% aqueous ammonia manufactured by Wako Pure Chemical Industries, Ltd. was added to the glycolamide containing glycolic acid aqueous solution (GA = 40 wt%, GAM = 3800 wt ppm / GA) prepared by the method of Reference Example 3 above, and the ammonium ion concentration Was adjusted to 950 ppm by weight. The prepared solution was passed through the regenerated strongly acidic cation exchange resin under the conditions of 80 ° C. and SV = 0.9, and the outlet solution was collected and analyzed by a fraction collector to obtain a breakthrough curve of glycolamide and ammonium ions. The results are shown in FIG.

[Examples 19 and 20 and Comparative Example 5]
About 100 mL of the crude glycolic acid aqueous solution recovered in Examples 11 to 13 was subjected to anion exchange purification and cation exchange purification to obtain purified glycolic acid. In anion exchange purification, the glass column (12φ x 300 mmH) is charged with a weakly basic anion exchange resin (IRA96SB) manufactured by Organo, and 400 mL of 2N aqueous sodium hydroxide solution is passed through with SV = 4 for regeneration treatment. And thoroughly washed with distilled water. Next, the crude glycolic acid aqueous solution was passed under conditions of 40 ° C. and SV = 2 to recover the glycolic acid aqueous solution. Furthermore, in cation exchange purification, the glass column (12φ x 300 mmH) is charged with a strongly acidic cation exchange resin (IRA120B) manufactured by Organo, and 400 mL of 2N aqueous sodium hydroxide solution is passed through with SV = 4 for regeneration treatment. And thoroughly washed with distilled water. Next, the crude glycolic acid aqueous solution after the anion exchange purification was passed through under the conditions of 40 ° C. and SV = 2 to recover the purified glycolic acid aqueous solution. Table 4 shows the analytical results of the purified glycolic acid aqueous solutions collected.

  Part of the resulting aqueous glycolic acid solution was charged into a 50 mL eggplant flask, and after substitution with nitrogen, heating was started under a nitrogen flow, and the temperature was raised from 170 ° C. to 200 ° C. while stirring with a stirrer at normal pressure. The condensation reaction was carried out while distilling off. Subsequently, the pressure was reduced to 40 mmHg with a vacuum pump, and the mixture was heated at 200 ° C. × 2 Hr to remove low boiling substances such as unreacted glycolic acid. Table 4 shows the evaluation results of the degree of coloring of the obtained prepolymer. Subsequently, the temperature was raised to 260 ° C., and the degree of vacuum was increased to 3 to 5 mmHg to carry out the depolymerization reaction. The distillate was recovered with a cooling trap with ice water. The composition of the recovered liquid was implemented by the above gas chromatography, but no peak other than glycolide was observed in any of them. Table 4 shows the evaluation results of the degree of coloring of the recovered liquid and the residual liquid in the flask.

  According to the present invention, carboxylic acid can be produced from a crude carboxylic acid aqueous solution containing carboxylic acid amide as an impurity. According to the present invention, a carboxylic acid amide contained as a reaction by-product in a crude carboxylic acid aqueous solution obtained by desalting an aqueous carboxylic acid ammonium salt solution obtained by a hydrolysis reaction of a nitrile compound, in particular, By converting to ammonium, the quality of the carboxylic acid finally produced can be increased.

Claims (16)

A method for producing a carboxylic acid, comprising: desalting a crude aqueous solution of a carboxylic acid ammonium salt containing a carboxylic acid amide, and then hydrolyzing the carboxylic acid amide by contacting with a solid acid catalyst. The method for producing a carboxylic acid according to claim 1, wherein, in the step of hydrolyzing the carboxylic acid amide, the carboxylic acid amide is reduced to 500 [weight ppm / carboxylic acid] or less. The method for producing a carboxylic acid according to claim 1 or 2 , wherein the crude carboxylic acid aqueous solution is obtained by a hydrolysis reaction of a corresponding nitrile compound. The method for producing a carboxylic acid according to claim 3 , wherein the hydrolysis of the nitrile compound is carried out by an enzyme catalyst using a combination of nitrilase and / or nitrile hydratase and amidase. The method for producing a carboxylic acid according to claim 3 , wherein the hydrolysis of the nitrile compound is performed by nitrilase. The method for producing a carboxylic acid according to claim 4 or 5 , wherein the nitrilase is derived from the genus Acinetobacter. The method for producing a carboxylic acid according to claim 6 , wherein the genus Acinetobacter is Acinetobactersp.AK226. The carboxylic acid according to any one of claims 1 to 7 , wherein the solid acid catalyst is at least one selected from the group consisting of zeolite, strongly acidic cation exchange resin, heteropoly acid salt, and layered metal oxide. Acid production method. The solid acid catalyst is a strongly acidic cation exchange resin, and in the step of hydrolyzing the carboxylic acid amide, the carboxylic acid amide is hydrolyzed by the solid acid catalyst to be used, and at the same time the ammonium carboxylate is formed. The method for producing a carboxylic acid according to any one of claims 1 to 8 , wherein the ammonium carboxylic acid salt is converted into a carboxylic acid and impurity cations are removed. The method for producing a carboxylic acid according to claim 9 , further comprising a step of removing impurity anions with an anion exchange resin after the step of producing the carboxylic acid. The method for producing carboxylic acid according to claim 9 , further comprising, after the step of producing the carboxylic acid, a step of removing impurity anions with an anion exchange resin and a step of removing impurity cations with a cation exchange resin. The method for producing an α-hydroxy acid according to any one of claims 1 to 11 , wherein the carboxylic acid is an α-hydroxy acid. The manufacturing method of the alpha-hydroxy acid of Claim 12 whose said alpha-hydroxy acid is lactic acid or glycolic acid. The manufacturing method of the alpha-hydroxy acid of Claim 12 whose said alpha-hydroxy acid is glycolic acid. A step of synthesizing an α-hydroxy acid oligomer using an aqueous solution of an α-hydroxy acid obtained by the method according to any one of claims 12 to 14 as a raw material, and depolymerizing the α-hydroxy acid oligomer, Obtaining a cyclic dimer ester. A method for producing a cyclic dimer ester. A method for producing a poly α-hydroxy acid, comprising a step of obtaining a poly α-hydroxy acid by a ring-opening polymerization reaction using the cyclic dimer ester obtained by the method according to claim 15 as a raw material.

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