JP2002187870A - Method for producing citric acid esters - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrially excellent method for producing a citric acid ester compound. SOLUTION: This method for producing a citric acid ester compound represented by general formula (3) [three R3s are the same or different and each an alkyl group] comprises reacting an citric acid compound represented by general formula (1) [R2 is a hydrogen atom or the like; R2 is an alkali metal] with an α-monohalogenated alkyl acetate represented by general formula (2) XCH2COOR3 [X is a halogen atom; R3 is an alkyl group] (the compound represented by general formula may be a single compound or a mixture in which R3 contains different groups). The method is characterized in that the hydrate of the citric acid represented by general formula (1) is used as the citric acid represented by general formula (1), the reaction between the citric acid represented by general formula (1) and the α-monohalogenated alkyl acetate represented by general formula (2) is carried out in the presence of a tertiary amine under reflux with a solvent azeotropic with water and water contained in the solvent is separated and removed when the solvent is refluxed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a citrate compound.

[0002]

2. Description of the Related Art Citric acid ester compounds are useful as plasticizers for various thermoplastic resins such as cellulose acetate and vinyl chloride.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide an industrially excellent method for producing a citrate compound.

[0004]

Means for Solving the Problems The present inventor has found that compatibility with thermoplastic resins is excellent, bleeding out from the resin is small, volatility during molding processing is low, and plasticizers of these resins are used. A method for producing a citrate compound represented by the general formula (3), which is useful as a compound, was studied. As a method for producing an ester compound, for example, British Patent Publication 93
No. 1,781 describes a method for producing phthalyl glycolate from phthalic acid half ester and α-halogenated acetic acid alkyl ester. First of the document
On the page, when phthalic anhydride is half-esterified and then neutralized, water is generated, and when phthalic acid half ester is reacted with α-halogenated acetic acid alkyl ester while water is present in the reaction system, α is formed by water. It is described that the halogenated acetic acid alkyl ester undergoes hydrolysis and the yield of the target compound is reduced. Further, it is described that it is difficult to remove generated water from a reaction system. Therefore, in the method for producing an ester compound using an α-halogenated acetic acid alkyl ester, it has been considered that it is desirable that water does not exist in the reaction system. Even when a hydrate is used as a raw material, water is generated in the system, so using a hydrate as a raw material causes problems such as a decrease in yield and a complicated reaction operation. Occurs,
Seemed undesirable. However, even when a hydrate of a citric acid compound is used as a raw material, a tertiary amine is used as a reaction catalyst and the reaction is carried out while removing water from the reaction system under reflux of a solvent capable of azeotroping with water. The present inventors have found that the target compound can be obtained in high yield and high purity by carrying out, and have completed the present invention.

That is, the present invention relates to the inventions described in the following items. Item 1 General formula (1)

[0006]

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[Wherein, R ¹ is a hydrogen atom or a group having 1 to 1 carbon atoms.
2 represents an aliphatic acyl group, and R ² represents an alkali metal. And a general formula (2) XCH ₂ COOR ³ (2) wherein X represents a halogen atom, and R ³ has 1 to 2 carbon atoms.
4 represents an alkyl group. (However, the compound of general formula (2) may be a single compound or a mixture in which R ³ has a different group.) With the general formula (3)

[0008]

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Wherein R ¹ is as defined above. Three R ³ represents an alkyl group having 1 to 24 carbon atoms the same or different. ]
A method for producing a citrate compound represented by the formula: wherein a hydrate thereof is used as the citrate compound represented by the general formula (1), and the citrate compound represented by the general formula (1) is The reaction with the α-alkylhalogenated alkyl acetate represented by the formula (2) is carried out in the presence of a tertiary amine under reflux of a solvent capable of azeotroping with water. A method comprising separating and removing contained water.
Item 2 The method for producing a citrate ester compound according to Item 1, wherein R ¹ is a hydrogen atom or an aliphatic acyl group having 1 to 5 carbon atoms, and R ³ is an alkyl group having 1 to 4 carbon atoms. Item 3
Item 1. The method for producing a citrate ester compound according to Item 1, wherein R ¹ is a hydrogen atom and R ³ is a methyl group or an ethyl group.
Item 4 The method for producing a citrate compound according to any one of Items 1 to 3, wherein the reaction temperature is 80 to 140 ° C. Item 5. The citrate ester compound according to any one of Items 1 to 4, wherein a part of the total amount of the tertiary amine is present in the reaction system at the start of the reaction, and the remainder is added after the start of the reaction. Production method.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the method of the present invention will be described specifically, but the method of the present invention is not limited thereto.

R ¹ is a hydrogen atom or an aliphatic acyl group. The aliphatic acyl group has 1 to 12 carbon atoms, and preferably 1 to 5 carbon atoms. Specific examples include formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, caproyl, enanthyl, capryloyl, pelargoyl, caprinoyl and the like. Preferably, formyl, acetyl, propionyl, butyryl and isobutyryl can be exemplified. R ¹ is more preferably a hydrogen atom or an acetyl group, and particularly preferably a hydrogen atom.

R ² is an alkali metal atom. As the alkali metal, sodium and potassium are preferable.

R ³ is a linear or branched alkyl group having 1 to 24 carbon atoms, particularly preferably an alkyl group having 1 to 4 carbon atoms. Specifically, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group,
Examples include an isobutyl group, a sec-butyl group, and a t-butyl group. R ³ is more preferably a methyl group or an ethyl group.

X represents a halogen atom, such as a chlorine atom, a bromine atom and an iodine atom.

The compound represented by the general formula (1) includes trisodium citrate, tripotassium citrate and the like. In the present invention, a hydrate thereof is used as the compound of the general formula (1). Hydrates include tripotassium citrate monohydrate, trisodium citrate dihydrate,
And the like are preferably exemplified. Of these, trisodium citrate dihydrate is particularly cheaply available.

Specific examples of the alkyl α-monohalogenated acetate represented by the general formula (2) include methyl monochloroacetate, ethyl monochloroacetate, propyl monochloroacetate and butyl monochloroacetate.

As the compound of the general formula (2), a single compound in which all of R ³ are the same may be used as a raw material, and two or three of the compounds of the general formula (2) having different R ³ may be used. It may be a mixture. When a single compound is used as the compound of the general formula (2), a compound of the general formula (3) having the same ^three R ³ is obtained. When a mixture is used as the compound of the general formula (2), three R ³ Are different from each other, or a compound of the general formula (3) in which two R ³ are the same and different from the remaining one R ³ is obtained. Examples of the mixture include a mixture of methyl monochloroacetate and ethyl monochloroacetate (a mixture having a molar ratio of about 1: 2), a mixture of methyl monochloroacetate and a mixture of ethyl monochloroacetate and propyl monochloroacetate (molar ratio of 1: 2).
1: 1 mixture) and the like can be used.

The amount of the α-alkyl monohalogenated acetate represented by the general formula (2) is not particularly limited.
It is preferable to use the citrate compound of the general formula (1) in an equivalent amount or more, and it is more preferable to use an excess amount with respect to the equivalent amount. It is preferable to use about 3 to 6 mol per 1 mol of the compound.

As the tertiary amine, a chain or cyclic aliphatic tertiary amine or aromatic amine is preferably used. Specifically, linear or cyclic aliphatic tertiary amines such as trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, and dimethylcyclohexylamine; pyridine,
And aromatic amines such as lutidine and ethylpyridine. Among these, triethylamine is preferred.

The amount of the tertiary amine to be used is generally about 0.01 to 1.0 mol, preferably about 0.1 to 0.5 mol, per 1 mol of the citric acid compound of the formula (1). .

Solvents that can be azeotropic with water include benzene (azeotropic point: 69.25 ° C.), toluene (85.0 ° C.), xylene (92-94.5 ° C.), chlorobenzene (90.2 ° C.), dichlorobenzene (90.2 ° C.). 133 ° C), ethylbenzene (92 ° C), propylbenzene (95 ° C) and other aromatic hydrocarbons that can be azeotroped, hexane (61.6 ° C), heptane (79.2 ° C), decane (134 ° C) C), and an alicyclic hydrocarbon capable of azeotroping with water, such as cyclohexane (69.5 ° C.). Among these, toluene is preferably used in the method of the present invention.

There are no particular restrictions on the amount of solvent used,
When the citric acid compound of the general formula (1) is a solid, an amount sufficient to stir the reaction raw material is required, and thus can be appropriately set according to the type of the raw material and the like. Usually, 5 to 5 parts by weight per 100 parts by weight of the citric acid compound of the general formula (1)
The amount is about 0 parts by weight, and about 7 to 33 parts by weight is preferable because of excellent volumetric efficiency.

In the method of the present invention, all of the compounds represented by the general formulas (1) and (2) are usually added in advance to the reaction vessel. The entire amount of the tertiary amine may be added to the reaction vessel, but a part of the tertiary amine (for example, about 0.1 to 10% by weight of the total amount) is added to the reaction vessel together with other raw materials from the beginning. In advance, the remaining amount depends on the reaction time,
It is desirable to add to the reaction system over about 20 hours.

Since the reaction between the compound of the general formula (1) and the compound of the general formula (2) is an exothermic reaction, immediately after the reaction starts, heat is received to decompose the alkyl α-monohalogenated acetate to generate hydrogen halide. However, this may cause a decrease in yield and purity. However, by charging the tertiary amine simultaneously with the raw materials at the beginning of the reaction, the effect of the hydrogen halide as a catching agent can be obtained, and the reaction can be completed without lowering the yield and purity. If a sufficient amount of a tertiary amine as a catching agent for hydrogen halide generated at the beginning of the reaction is charged, the remaining tertiary amine is gradually added to the reaction system as the reaction progresses. This is preferable because the reaction can be completed smoothly.

Usually, when a hydrate thereof is used as a citric acid compound, water of crystallization separates and water is present in the reaction system. If water of crystallization stays in the system, the alkyl ester of α-monohalogenated acetic acid is decomposed and hydrochloric acid is by-produced, resulting in a decrease in purity or a decrease in yield, which is not preferable. Therefore, it is conceivable that the hydrate of the citric acid compound is dehydrated in advance, but there is a problem that the operation becomes difficult because crystals of the anhydride are formed during the dehydration. Also,
It is industrially disadvantageous because it is necessary to dehydrate for a long time in order to prevent the formation of a lump. If the reaction is carried out under reflux of a solvent capable of azeotropic distillation with water as in the present invention, the separated water of crystallization evaporates together with the solvent in an azeotropic composition, so that water can be removed from the reaction system. The solvent containing water may be once distilled out of the reaction system, separated from the solvent and removed, and then returned to the reaction system again. As described above, if water is removed from the reaction system, even if a hydrate of the citric acid compound is used as a raw material, the yield decreases, the cost increases due to the generation of by-products, and the purity of the product decreases. There is no possibility that the problem of lowering will occur, nor will there be a problem that the physical properties of the obtained citrate compound will be inferior. The method of separating and removing water from the solvent containing water during the reflux is not particularly limited, and may be performed according to a conventional method. For example, since water and a solvent azeotropically evaporate and are distilled as an azeotropic composition by heating, the distillate is led to a recovery device provided outside the system, and water is separated from the distillate in the device. The water can be separated by returning the solvent into the system.

When the reaction raw materials are a solid and a liquid, the reaction rate tends to be controlled by stirring. Therefore, it is preferable to sufficiently stir the reaction to increase the reaction rate. Is desirably set not to be retained in the system.

The reaction can be carried out under normal pressure or reduced pressure, but is preferably carried out under reduced pressure. The degree of decompression is 1
It is preferably about 3.3 to 101.3 kPa, and 40 to 80 kPa.
About kPa is more preferable.

The reaction temperature (the temperature in the reaction system) may be appropriately set according to the type of solvent used, the pressure, and the like.
~ 140 ° C, preferably 100 ~ 130
C. is more preferable. A temperature of about 140 ° C. or lower is preferable because impurities due to side reactions are hardly produced as by-products.

More specifically, when toluene is used as the solvent, the reaction temperature is adjusted to about 100 to 130 ° C., and the pressure in the reaction system is adjusted to about 53.3 to 80.0 MPa. preferable.

The reaction time can be appropriately set according to the type and amount of the raw materials, but is usually about 1 to 30 hours, preferably about 10 to 20 hours.

The compound of the general formula (3), which is a reaction product, can be easily isolated and purified by usual separation and purification means, for example, recrystallization, solvent extraction, column chromatography and the like. it can. As the compound of the general formula (1), an alkali metal salt is used, and a salt is by-produced.
After the completion of the reaction, it is desirable to wash and remove it. Further, since an amine salt is by-produced, it is preferable that after the reaction is completed, washing with a dilute acid is performed, followed by neutralization with an alkali and washing with water.

[0032]

According to the method of the present invention, even when a hydrate of a citric acid compound is used as a raw material, the yield is reduced, the cost is increased due to the generation of by-products, and the purity of the product is reduced. The citrate compound obtained is also excellent in physical properties.

[0033]

Example 1 A four-necked flask was equipped with a stirrer, a thermometer, an additional funnel, a water separator, a condenser, 294.1 g (1.0 mol) of trisodium citrate dihydrate, monochloroacetic acid 404.3 g (3.3 mol) of ethyl, 0.3 g (0.003 mol) of triethylamine, 77.5 g of toluene
While stirring under vacuum of 53.3 kPa.
Heated to 10 ° C. 10. When toluene starts refluxing in the external circulating water recovery device and stabilizes, triethylamine
8 g (0.117 mol) were added in 10 hours. 16 hours after the start of the reaction, water of crystallization of sodium citrate dihydrate 3
Since 6.0 g (2.0 mol) was recovered, the reaction was terminated after aging for 1 hour. After completion of the reaction, the mixture was cooled to 40 ° C., and 560 g of a 1% hydrochloric acid aqueous solution was added to remove by-produced sodium chloride and quaternary ammonium salt of triethylamine. Next, 14.2 g of sodium carbonate was added to the oil layer.
(0.135 mol) and 185 g of water were added for neutralization. Further, after the oil layer was washed with 185 g of water,
The solvent was recovered at a temperature of up to 5.33 kPa, followed by 1 hour of steam distillation to obtain the desired compound (412.4).
g, yield 91.5%). In the general formula (3), R ¹
It was confirmed by NMR and IR that a compound in which = hydrogen atom and R ³ = ethyl group was obtained. The purity by area percentage of gas chromatography (GC) is 92.1%,
The acid value was 0.126 (KOHmg / g). Examples 2 to 4 Example 1 was repeated except that the reaction conditions were changed to the methods described in Table 1.
Synthesis was performed in the same manner as described above.

[0034]

[Table 1]

Comparative Example 1 A four-necked flask was equipped with a stirrer, a thermometer, an additional funnel and a condenser, and trisodium citrate dihydrate 29
4.1 g (1.0 mol), monochloroethyl acetate 40
4.3 g (3.3 mol), 0.3 g of triethylamine
(0.003 mol) and 77.5 g of toluene, and heated to 120 ° C. while stirring at 101.3 kPa under normal pressure. When temperature stabilizes, triethylamine 1
1.8 g (0.117 mol) were added in 10 hours. The reaction was completed 16 hours after the start of the reaction. Since no water separator was attached, recovery of water of crystallization of sodium citrate dihydrate was not performed. After completion of the reaction, the mixture was cooled to 40 ° C., and 560 g of a 1% aqueous hydrochloric acid solution was added to remove by-produced sodium chloride and quaternary ammonium salt of triethylamine. Next, 50.6 g of sodium carbonate (0.
(955 mol) and 185 g of water for neutralization. Further, after the oil layer was washed with 185 g of water, it was heated at 120 ° C.
The solvent was recovered under the conditions of up to 33 kPa, followed by 1 hour of steam distillation to obtain the target compound (208.7 g, yield: 46.4%). Gas chromatography (GC)
Was 71.2%, and the acid value was 0.093 (KOHmg / g).

Since the reaction was carried out while water of crystallization was present in the system, the yield and purity decreased.

Comparative Example 2 (Synthesis after Preliminary Dehydration of Crystallized Water) A four-necked flask was equipped with a stirrer, a thermometer, a water separator, a condenser, and 294.1 g of trisodium citrate dihydrate. 600 g of xylene was charged and heated to 140 ° C. while stirring at normal pressure to perform dehydration. When dehydration was performed during the dehydration so that the anhydride crystals did not solidify, 31.2 g (1.73 mol) of water was recovered by dehydration for 15 hours. Thereafter, 515 g of xylene was distilled off at normal pressure. Then, 404.3 g of ethyl monochloroacetate
(3.3 mol), 0.3 g of triethylamine (0.00
3mol), 77.5 g of toluene, and 53.3 kP
The mixture was heated to 110 ° C. while stirring in the vacuum state of a. When the xylene / toluene mixed solvent started to reflux and became stable, 11.8 g (0.117 mol) of triethylamine was added in 10 hours. Sixteen hours after the start of the reaction, 4.8 g (0.27 mol) of the remaining water of crystallization in sodium citrate was recovered, and after aging for one hour, the reaction was terminated. After completion of the reaction, the mixture is cooled to 40 ° C.
60 g were added to remove by-product sodium chloride and quaternary ammonium salt of triethylamine. Next, 6.9 g (0.130 mol) of sodium carbonate and 185 of water were added to the oil layer.
g was added for neutralization. Further, after the oil layer was washed with 185 g of water, the solvent was recovered under the conditions of 120 ° C. and 5.33 kPa, followed by 1 hour of steam distillation to obtain the target compound (405.1 g, yield 90.0%). I got The purity by area percentage of gas chromatography (GC) was 86.0%, and the acid value was 0.632 (KOHmg /
g).

The method of preliminarily dehydrating a hydrate is not suitable as an industrial production method because a long time of 15 hours is required for preliminary dehydration.

[0039]

[Table 2]

[Brief description of the drawings]

FIG. 1 is a chart of ¹³ C-NMR of the compound obtained in Example 1.

FIG. 2 is a chart of ¹ H-NMR of the compound obtained in Example 1.

FIG. 3 is an IR chart of the compound obtained in Example 1.

Claims (5)

[Claims] 1. A compound of the general formula (1) [Wherein, R ¹ represents a hydrogen atom or an aliphatic acyl group having 1 to 12 carbon atoms, and R ² represents an alkali metal. And a general formula (2) XCH ₂ COOR ³ (2) wherein X represents a halogen atom, and R ³ has 1 to 2 carbon atoms.
4 represents an alkyl group. (However, the compound of general formula (2) may be a single compound or a mixture in which R ³ has a different group.) And reacting with the general formula (3) Wherein R ¹ is the same as described above. Three R ³ represents an alkyl group having 1 to 24 carbon atoms the same or different. A method for producing a citric acid ester compound represented by the general formula (1), wherein a hydrate thereof is used as the citric acid compound represented by the general formula (1), The reaction with the α-alkylhalogenated acetate represented by the general formula (2) is carried out in the presence of a tertiary amine under reflux of a solvent capable of azeotropic distillation with water. A method comprising separating and removing water contained in water. 2. The method according to claim ¹ , wherein R ¹ is a hydrogen atom or an aliphatic acyl group having 1 to 5 carbon atoms, and R ³ is an alkyl group having 1 to 4 carbon atoms. . 3. The method for producing a citrate compound according to claim 1, wherein R ¹ is a hydrogen atom and R ³ is a methyl group or an ethyl group. 4. The method for producing a citrate ester compound according to claim 1, wherein the reaction temperature is 80 to 140 ° C. 5. The quench according to claim 1, wherein a part of the total amount of the tertiary amine is present in the reaction system at the start of the reaction, and the remainder is added after the start of the reaction. A method for producing an acid ester compound.