WO1999000350A1

WO1999000350A1 - Process for producing free acids from ammonium carboxylates

Info

Publication number: WO1999000350A1
Application number: PCT/JP1998/002844
Authority: WO
Inventors: Kouichi Hayakawa; Masatsugu Hatayama
Original assignee: Nippon Soda Co., Ltd.
Priority date: 1997-06-26
Filing date: 1998-06-25
Publication date: 1999-01-07
Also published as: AU7933798A

Abstract

A process for producing carboxylic acids, characterized by heating an ammonium carboxylate of the general formula (1) RCOO-NH4+: (wherein R is hydrogen, alkyl which may be substituted, cycloalkyl which may be substituted, aryl which may be substituted, or saturated or unsaturated heterocyclic group which may be substituted) in an ether solvent having two or more ether bonds such as ethylene glycol dimethyl ether to liberate ammonia and removing ammonia by distillation.

Description

Description --- Method for producing free acid from ammonium carboxylate-Technical field:

INDUSTRIAL APPLICABILITY The present invention is industrially important as a raw material for synthesizing various pharmaceuticals, agricultural chemicals, organic electronic materials, and the like, and some carbon dioxides used as food additives or feed additives are used. The present invention relates to a method for producing an acid.

Background art:

The most common method of producing a free acid from a carboxylic acid ammonium salt is a method of neutralizing with a mineral acid such as sulfuric acid.In this case, a mineral acid salt such as ammonium sulfate is produced in an equivalent amount or more. Mineral salts have to be treated, which creates a large amount of waste management problems.

As a method of preventing the generation of mineral salts as waste, a method of adding an alcohol to an ammonium salt of a carboxylic acid and esterifying it (Japanese Patent Application Laid-Open No. 7-194873) is used. There is a method in which an ester is obtained once and then hydrolyzed using an acid catalyst. However, this method requires the use of alcohol and acid catalysts as new additives, and these additives must be recovered, which is not an industrially advantageous method. .

Also, a method of obtaining unsaturated fatty acids by adding a small amount of water to an ammonium salt of unsaturated fatty acids and freeing ammonia while completely refluxing in an organic solvent at a temperature of 80 or more to remove ammonia (UK Patent Publication No. 2) Add an organic solvent that azeotropes with water to a 10 to 50% aqueous solution of (meth) acrylic acid ammonium salt, and heat at 60 to 100 to azeotropically distill the water and simultaneously release ammonia To obtain (meth) acrylic acid by distilling off

— 1 15 3 17), a method of obtaining an acidic amino acid by heating and heating water while supplying water to a 10 to 80% aqueous solution of an ammonium acid acid ammonium salt (water). JP 7

-3 3 0 6 9 6) is known.

In these methods, the target carboxylic acid exhibits a high acid dissociation constant, so that it can be easily deammonified in principle.However, in the case of a strong acid having a pKa of 4 or less, a carboxylic acid ammonium salt is used. The degree of dissociation of ammonia from water is small, it is difficult to remove ammonia, and it takes a long time to remove most of the ammonia. Or requires the addition of large amounts of organic solvents or large amounts of water. When the present inventors applied these three methods to the production of carboxylic acids having a pKa of 4 or less, in any of the methods, 50% or more of the carboxylic acid ammonium salt remained, and the industrial production method and Was inappropriate. Disclosure of the invention:

An object of the present invention is to provide a method for producing a free acid of a carboxylic acid from an ammonium salt of a carboxylic acid in a high yield, which is a method which does not cause a problem of waste treatment and which is applicable to carboxylic acid having a high acidity. To provide.

As a result of the present inventor's intensive search for an organic solvent capable of efficiently releasing an ammonium salt even with a carboxylic acid ammonium salt having a high acidity, the use of an ether solvent having two or more ether bonds is particularly effective. I found something.

That is, the present invention relates to the general formula [1]

RC 0 0-NH ₄ ⁺ [1]

(Wherein, R is a hydrogen atom, an alkyl group which may have a substituent, an alkyl group which may or may not have a substituent, an aryl group or a substituent which may have a substituent Represents a saturated or unsaturated heterocyclic group which may have the following formula:) The carboxylic acid ammonium salt represented by the formula is heated in an ether solvent having two or more ether bonds to liberate ammonia and eliminate distillation. This is a method for producing a carboxylic acid.

In addition, in particular, when the length is the general formula [2 3

0 H

1 [2]

R 'C H-

(In the formula, R ′ represents a hydrogen atom, a C 1-6 alkyl group which may have a substituent, or an aryl group which may have a substituent.) [1] is excellent as a method for producing a carboxylic acid from a carboxylic acid ammonium salt represented by the following formula:

The ammonium salt of a carboxylic acid according to the present invention can be produced by the biological or catalytic hydrolysis of the corresponding nitrile amide. Further, when carboxylic acid is obtained as a metal salt by a hydrolysis reaction of nitrile or amide with an inorganic base or a microbial reaction, for example, Japanese Patent Application Laid-Open No. Show It can be converted to ammonium salt in the same way. That is, the metal of the carboxylic acid - by adding NH ₃ and C 0 ₂ in an aqueous solution of a salt may be converted into carboxylic acid-en ΐ Niu unsalted, it can be subjected to the present invention.

In addition, after the hydrolysis of nitrile amide with a mineral acid, an ammonium carboxylate can be obtained by adding an inorganic base. However, in this case, a large amount of mineral salts is by-produced.

BEST MODE FOR CARRYING OUT THE INVENTION

Examples of the substituent of R of the carboxylic acid represented by the general formula [1], which is an object of the present invention, include an alkyl group, an alkoxy group, an alkylthio group, an acyl group, a halogen such as chlorine, bromine, a hydroxy group, Examples include an amino group, a nitro group, a thiol group, a phenyl group, and a heterocyclic group. Examples of the heterocyclic group for R include a 3 to 7-membered ring containing at least one kind of nitrogen, oxygen or sulfur as a hetero atom.

Examples of the substituent of R ′ of the carboxylic acid represented by the general formula [2], which is an object of the present invention, include a halogen such as an alkoxy group, an alkylthio group, an acyl group, chlorine, and bromine, and an aryl group. Can be

Specifically, for example, acetic acid, chloroacetic acid, benzoic acid, paraaminobenzoic acid, phenylacetic acid, chenylacetic acid, glycolic acid, lactic acid, mandelic acid, α-hydroxybutyric acid, α-hydroxyisobutyric acid, α—Hydroxy— 4—Methylthiobutyric acid, β-Hydroxypropionic acid, / 3 , Nicotinic acid, picolinic acid and the like.

In the practice of the present invention, the carboxylic acid ammonium salt is converted to an ether bond.

Ammonia is liberated by heating in an ether solvent having two or more solvents, distilling out together with the ether solvent and, in the case of using an aqueous solution, the mixed vapor of water, The free carboxylic acid is obtained by distilling off. The ether solvent distilled off can be recovered and used as it is. During the reaction, the distillate can be collected with a condenser, and a very small amount of dissolved ammonia can be degassed, and then the ether solvent and water can be separated and collected. Most of the distillate ammonia can be recovered from the condenser tower as gas. In the present invention, the method of the present invention does not require the presence of water, and the carboxylic acid ammonium salt used can be used in an aqueous solution when it can be obtained in an aqueous solution, and a stable carboxylic acid ammonium salt is used as it is. be able to. When used in an aqueous solution, it is preferable that the amount of water is small because the water is distilled.

A series of these operations, that is, desorption and recovery of ammonia, acquisition of free carboxylic acid, and recovery and use of solvent, can be continuous, and the efficiency of producing free acid from ammonium salt of carboxylic acid by continuous operation can be improved. Is further improved. Figure 1 shows the continuous process as a flow chart.

Figure 1

Hara

Supplement

Water treatment process

Sugar tower 1 Separation tank Rectifier 2 Rectifier 3

Reaction tower) (stribbing)

As the reaction device, various distillation devices can be used, but those having a stirrer to increase the evaporation area and those forming a liquid film are particularly advantageous. The reaction temperature is usually in the range of 60 to 200 ° C, preferably 80 to 150 ° C. The end point of the reaction is the time at which distilling of the mon monies stops. During the reaction, by introducing an inert gas, the distillation efficiency of ammonia can be improved and the amount of the distilled solvent can be reduced. The reaction system usually reacts under atmospheric pressure, but may be in a pressurized state or a reduced pressure state in order to adjust the reaction temperature depending on the ether solvent used.

Examples of the ether solvent having two or more ether bonds used in the reaction include ethylene glycol diethylene glycol, ethylene glycol gelatin ester, and ethyl alcohol. Lethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diethylene glycol dimethyl ether, diethylene glycol dibutyl ether, triethylene glycol dimethyl ether, triethylene glycol divinyl ether, propylene glycol dimethyl ether, dioxane, Examples thereof include lioxane, 2,2-dimethoxypropane, 1,1-diethoxycetane, 1,1,2-trimethoxetane and the like.

When a solvent that is difficult to separate from water is used among these solvents, the use of the ether solvent used is mixed with an inert solvent that separates from water, so that the solvent recovery operation is easy. Become. Further, by using a mixed solvent, the amount of expensive ether solvent used can be reduced, and the economic efficiency can be improved. Examples of the solvent used by being mixed with the ether solvent include hydrocarbon solvents such as toluene, xylene and mesitylene, and chlorine solvents such as dichloroethane.

The amount of ether solvent used depends on the type of solvent, the type of carboxylic acid ammonium salt, etc., but in the case of a batch type, the weight ratio of ether solvent / ammonium carboxylate is usually 1 to 10 times. Is selected.

When a mixed solvent is used, the mixing ratio is selected in the range of 0.2 to 10 times by weight based on the ether solvent.

In the reaction, carboxylic acid amide may be formed as a by-product. However, by selecting an organic solvent or increasing the evaporation area, the by-product rate can be suppressed to 1% or less. In addition, in the production of hydroxy acids, polyesters may be formed as a by-product due to dehydration condensation between molecules, but this is also reduced to 5% or less by selecting an organic solvent or increasing the evaporation area. Can be suppressed.

If the carboxylic acid ammonium salt is obtained as an aqueous solution, it may be used for the reaction without being concentrated, but it is better to reduce the water content as much as possible to remove ammonia more efficiently and to reduce the by-products. Generation is also suppressed.

Hereinafter, the present invention will be described specifically with reference to examples. Carboxylic acid and carboxylic acid amides were analyzed by high performance liquid chromatography, and ammonia was analyzed by the method of ultraviolet absorbance measurement using NADH to glutamate dehydrogenase (Methods of Enzymatic Analysis). , Bergmeyer HU ed., 3rd ed., Vol.8, pp.454-461) Quantification.

[Example 1]-A straight tube was attached to a 50 ml flask equipped with a stirrer, a thermometer, and a gas inlet tube, and a fractionation head equipped with a thermometer and a reflux condenser was attached to the top of the straight tube. . In this 5 O ml flask, α-hydroxy-4-methylthiobutyronitrile was subjected to biological hydrolysis and then concentrated, and α-hydroxy-4-methylthiobutyric acid ammonium salt, 21.8 millimoles, was added. An aqueous solution containing 6.36 g (water content: 4.2.9 wt%) and 30 ml of diethylene glycol dimethyl ether were added, and the mixture was heated and stirred in an oil bath at about 14.5. At this time, nitrogen gas was introduced into the reaction solution at a rate of 100 m1 / min. Approximately 15 minutes after the start of the heating, water previously present in the raw material was distilled off as an azeotropic mixture with diethylene glycol dimethyl ether. Thereafter, the temperature of the reaction solution gradually increased and became constant at about 130 ° C., and the mixture was stirred at this temperature for 2 hours while introducing nitrogen gas. During this time, ammonia gas was discharged from the top of the reflux condenser, and the total amount of distillate was 4.5 ml. Diethylenglycol dimethyl ether was distilled off from the reaction solution remaining in the 50 ml flask under reduced pressure, and 5 ml of water was further added and distilled off under reduced pressure to completely drive off dimethyleneglycol dimethyl ether. Got the oil. As a result of high-performance liquid chromatography analysis and ammonia analysis of this oil, the residual rate of ammonia was 0.12%, and the by-product rate of α-hydroxy-4-methylthiobutyric acid amide was 0.1%. The linear by-product of α-hydroxy-4-methylthiobutyric acid was 79% and the by-product ratio was 1.3%. The yield of free acid with respect to the ammonium salt charged with α-hydroxy-14-methylthiobutyric acid was 96.3%.

[Comparative Example 1]

The method was carried out according to the method described in British Patent No. 9673352. In a 5 O ml flask equipped with a stirrer, a thermometer, and a reflux condenser, α-hydroxy-4-methylthiobutyric acid ammonium salt (3.802) and water (1.0 ml) were charged to obtain a homogeneous solution. To this, 23.O ml of toluene was added, and the mixture was heated and refluxed while being stirred in an oil bath at 120 ° C. The temperature of the reaction solution was 100 ° C. to 103 ° C., and ammonia gas was generated from the top of the reflux condenser. After heating and refluxing for 4 hours, toluene and water were distilled off under reduced pressure to obtain 3.82 g of an oil. Table 2 shows the analysis results. From the analysis results, the residual rate of ammonia is 70 0.3%, the by-product rate of α-hydroxy-14-methylthiobutyrate amide is 2.

3%, and the linear by-product of α-hydroxy-14-methylthiobutyric acid is 2

2%. The yield of the free acid with respect to the ammonium salt charged with α-hydroxy-4-methylthiobutyric acid was 28. 2%.

[Comparative Example 2]

It carried out according to the method of Unexamined-Japanese-Patent No. 54-1111517. In a 20 O ml flask equipped with a stirrer, thermometer, simple distillation column (inner diameter 1 O mm, height 10 cm), and a cooler, α-hydroxy-4—ammonium salt of methylthiobutyrate 5.1 A 50% by weight aqueous solution containing 7 g and 115 ml of toluene were added, and the mixture was heated and stirred while introducing a small amount of dry air into the gas phase. Ammonia gas was generated at the same time as the azeotropic mixture of toluene and water was distilled off. The azeotropic distillation stopped about 40 minutes after the start of the distillation, and the reaction was completed about 10 minutes after the distillation of almost only toluene. The total amount of the distillate was 64.5 g, and the total amount of the solution after the reaction was 58.8 g. After the reaction, the solution was concentrated under reduced pressure to obtain 5.6 g of a foil. According to the analysis results, the residual ratio of ammonia was 56.6%, the by-product ratio of α-hydroxy 4-methylthiobutyrate amide was 0.5%, and α-hydroxy-

The by-product of the linear dimer of 4-methylthiobutyric acid was 3.2%. The yield of free acid with respect to the ammonium salt charged with 4-hydroxy-4-methylthiobutyric acid was 37.2%.

[Comparative Example 3]

This was carried out according to the method described in JP-A-7-330696. In a 5 O ml flask equipped with a stirrer, thermometer, dropping port, simple distillation column (inner diameter 1 Omm, height 10 cm), and a condenser, ct-hydroxy-4-ammonium salt of methylthiobutyrate 10 Charge 35 g of water and 12 m1 of water, and continuously supply water preheated to 70 ° C at 20 m1 Zhr while flowing a small amount of nitrogen from the cabinet under atmospheric pressure. The bottom flask was heated in an oil bath at 150 ° C, and the amount of retained liquid was kept almost constant at a top distilling temperature of 99 to 100 and a distilling speed of 20 m1 / hr. The ammonia water was distilled off, and a total of about 80 m 1 of ammonia water was obtained in about 4 hours. The total amount of the solution after the reaction was 21.9 m 1. According to the analysis results, the residual ratio of ammonia was 70.8%, and the yield of free acid with respect to the ammonium salt charged with α-hydroxy-14-methylthiobutyric acid was 24. 8%.

[Examples 2 to 14]-Based on the operation method of Example 1, the reaction was carried out by changing the raw materials, the solvent, and the reaction conditions, and the results shown in Tables 1 and 2 were obtained. In the table, the residual ammonia ratio, amide by-product ratio, and free acid yield are the molar yields relative to the raw material ammonium salt.

Table 1

(Note) HMB A: α-Hydroxy-4-methylthiobutyric acid Solvent type A: Ethylene glycol dimethyl ether

* 1: Pressurized reaction B: Diethylene glycol dimethyl ether * 2: Reduced pressure reaction C: Ethylene glycol dimethyl ether

D: Triethylene glycol dimethyl ether E: Dioxane

Table 2

The invention's effect :

The method of the present invention is suitable from an industrial point of view and is fertile for various reasons;

B) When producing free carboxylic acid from carboxylic acid ammonium, ammonia can be recovered as ammonia gas or a concentrated aqueous solution of ammonia, so that it has high utility value and does not generate ammonium salt waste.

Mouth) There is no need to add new substances such as catalysts and additives for neutralization, which is advantageous in manufacturing cost.

Claims

Scope of claim--1. General formula [1] ―

RC 0 0-NH ₄ + [1]

(Wherein, R represents a hydrogen atom, an alkyl group which may have a substituent, a cycloalkyl group which may have a substituent, an aryl group or a substituent which may have a substituent, The carboxylic acid ammonium salt represented by) is heated in an ethereal solvent having two or more ether bonds to liberate ammonia and eliminate distillate. A method for producing a carboxylic acid, comprising:

2. The length is the general formula [2]

O H

I [2]

R 'C H-

(Wherein, R ′ represents a hydrogen atom, a C 1-6 alkyl group which may have a substituent, or an aryl group which may have a substituent). The manufacturing method described.

3. The process according to claim 1, wherein the ether solvent is ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, ethylene glycol getyl ether, triethylene glycol dimethyl ether or dioxane.

4. The method according to claim 1, wherein an inert solvent which separates from water is mixed with an ether solvent and used.

INTERNATIONAL SEARCH REPORT International application No.

PCT / JP98 / 02844

A. CLASSIFICATION OF SUBJECT MATTER Ichi

Ent, Cl ⁶ C07C51 / 02, C07C53 / 08, C07C63 / 06, C07D213 / 08, C07C323 / 52,

C07B41 / 08

According to International Patent Classification (IPC) or to both national classification and IP

B. FIELDS SEARCHED

Minimum documentation searched (classification system followed by classification symbols)

Int.CI ⁶ C07C51 / 02, C07C53 / 08, C07C63 / 06, C07D213 / 08, C07C323 / 52,

C07B41 / 08

Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched

Electronic data base consulted during the international search (name of data base and, where practicable, search terms used)

C. DOCUMENTS CONSIDERED TO BE RELEVANT

Category * Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No.

X JP, 61-2055, B2 (Nitto Chemical Industry Co., Ltd.) L-4

22 January, 1986 (22.01.86),

Refer to Claims; page 2, column 3, lines 27, 28

(Family: none)

A JP, 61-50937, A (Asahi Chemical Industry Co., Ltd.) L-4

13 March, 1986 (13.03.86),

Refer to Claims page 2, lower right column,

lines 2 to 19 (Family: none)

[I Further documents are listed in the continuation of Box C. ι | See patent family annex.

* Special categories of cited documents: "T" later document published after the international filing date or priority "A" document denning the general state of the art which is not date and not in conflict with the application but cited to understand considered to be of particular relevance the principle or theory underlying the invention

E earlier document but published on or after the international luing date "X" document of particular relevance; the claimed invention cannot be L document which may throw doubts on priority claim (s) or which is considered novel or cannot be considered to involve an inventive step cited to establish the publication date of another citation or other when the document is taken alone

special reason (as specified) "Y" document of particular relevance; the claimed invention cannot be "O" document referring to an oral disclosure, use, exhibitio or other considered to involve an inventive step when the document is means combined with one or more other such documents, such combination

P document published prior to the international filing date but later than being obvious to a person skilled in the art

the priority date claimed "&" document member of the same patent family

Date of the actual completion of the international search Date of mailing of the international search report

22 September, 1998 (22.09.98) 6 October, 1998 (06 · 10, 98)

Name and mailing address of the ISA / Authorized officer

Japanese Patent Office

Facsimile No. Telephone No.

Form PCT / ISA / 210 (second sheet) (July 1992)