WO2007020816A1 - Process for producing difluoroacetic acid salt - Google Patents

Abstract

A process for producing a metal difluoroacetate which comprises reacting a 1-alkoxy-1,1,2,2-tetrafluoroethane represented by the formula [1]: [Chemical formula 4] HCF2 CF2 OR1 (1) (wherein R1 represents C1-20 linear or branched alkyl) with a C1-20 alcohol and either a metal hydroxide or a metal alkoxide.

Description

 Specification

 Method for producing difluoroacetate

 Technical field

 TECHNICAL FIELD [0001] The present invention relates to a method for producing difluoroacetate useful as an intermediate for medical and agricultural chemicals and an intermediate for functional materials.

 Background of the Invention

 [0002] As a method for producing acetate, a method of reacting acetic acid with a metal hydroxide has been widely known. On the other hand, with respect to a method for producing an acetate having a fluorine atom, for example, a difluoroacetate which is a subject of the present invention, difluoroacetic acid is conventionally known as in the case of an acetate without a fluorine atom. In general, it is produced by reacting a metal hydroxide with a metal hydroxide, and examples other than this method have been known.

 Here, as a method for producing difluoroacetic acid, for example, in Patent Document 1, dichloroacetic acid chloride is reacted with a secondary amine to form N, N disubstituted dichloroacetic acid amide, and the N, N disubstituted dichloroacetic acid is produced. Disclosed is a method for producing difluoroacetic acid by reacting an amide with a fluorinating agent such as an alkyl metal fluoride to form an N, N disubstituted difluoroacetamide, and then hydrolyzing the N, N disubstituted difluoroacetamide. ing.

 [0004] In Patent Document 2, 1, S-difluoro-2-troethane is hydrolyzed in water to obtain difluoroacetic acid S. In Non-Patent Document 1, dichloroacetic acid methyl ester is converted to a fluoride such as KF. And a method for producing difluoroacetic acid by hydrolyzing methyl fluoroacetate after fluorination with difluoroacetic acid methyl ester is disclosed.

 [0005] On the other hand, Patent Document 3 and Non-Patent Documents are disclosed as conventional techniques related to the present invention using 1 alkoxy 1,1,2,2-tetrafluoroethane represented by the formula [1] which is a raw material of the present invention. Reference 2 [This is a 1-no-recoxi 1, 1, 2, 2--Terrafnore old Roetan, Anolemina (AI O)

 Gas phase reaction in the presence of a metal oxide catalyst such as 2 3

 2

OF) and further reacting with alcohols to produce difluoroacetic acid ester (HCF COOR

 2

. A method in which R is an alkyl group having 1 to 4 carbon atoms is disclosed.

Patent Document 1: JP-A-6-228043 Patent Document 2: JP-A-60-041634

 Patent Document 3: JP-A-8-92162

 Non-patent literature l: Rec. Trav. Chim., 65 卷, 427, 1947

 Non-Patent Document 2: Reports Res. Lab. Asahi Glass Co., ltd., Vol. 47, 69-79, 1997

 Summary of the Invention

 [0006] As described above, as a method for producing difluoroacetate, the method power S of reacting the corresponding difluoroacetic acid and metal hydroxide is considered to be the most common, but at that time, it is the raw material. Method power to obtain difluoroacetic acid was not always easy. For example, in the method of Patent Document 1, a fluorinating agent that is difficult to handle must be used, and in addition, a large amount of waste such as inorganic salts after the reaction is by-produced. Furthermore, since multiple steps were taken to obtain difluoroacetic acid, this was not advantageous for large-scale production. In the method of Patent Document 2, since sulfuric acid is used for hydrolysis, there is a problem that a large amount of sulfuric acid waste liquid is generated. In the methods of Patent Document 3 and Non-Patent Document 2, 1-alkoxy-1, 1, 2, 2-tetrafluoroethane represented by the formula [1], which is a raw material of the present invention, is converted into a metal oxide. In order to obtain difluoroacetate in Patent Document 3, Non-Patent Document 1, and Non-Patent Document 2, it is necessary to conduct a gas phase reaction using a physical catalyst and to derive once to another compound. After further hydrolysis of the ester to obtain difluoroacetic acid, a multi-step process was required, for example, the metal hydroxide had to be reacted.

 As described above, the above production method for obtaining difluoroacetate is difficult to produce difluoroacetate as a raw material, and a method for producing difluoroacetate by a more advantageous and efficient method is required. It was.

 [0008] As a result of intensive studies, the present inventors have found that 1 alkoxy 1, 1, 2, 2-tetrafluoroethane represented by the formula [1]

 [Chemical 1]

HCF ₂ CF ₂ OR ¹ (Wherein R ¹ represents a linear or branched alkyl group having 1 to 20 carbon atoms) and a difluoroacetate salt by reacting with an alcohol having 1 to 20 carbon atoms and a metal hydroxide or metal alkoxide. The present invention has been found.

[0009] To date, a technique for producing a corresponding acetate salt of an alkoxyalkane compound having no fluorine atom in the same manner as in the present invention has not been known. For example, even if 1-alcoxetane is reacted with an alcohol having 1 to 20 carbon atoms and a metal hydroxide or metal alkoxide, the reaction does not proceed and no corresponding acetate is obtained (Comparative Example) (See 1).

 [0010] On the other hand, 1-alkoxy-1, 1, 2, 2-tetrafluoroethane, which is a raw material of the present invention, has a fluorine atom as a carbon atom. Due to the strong electron withdrawing property of the fluorine atom, the reactivity of the hydrogen atom bonded to the α-position carbon atom becomes more energetically unstable than that without the fluorine atom, and the alkoxyalkane has been conventionally used. Unlike the complex substrate, it was expected that it would be extremely difficult to produce the corresponding difluoroacetate salt, which has a greater tendency to induce side reactions.

 However, the inventors reacted alcohol and metal hydroxide with a reaction substrate having such a fluorine atom, so that no by-product was obtained at all, and the intended difluoroacetate was easily obtained. When it could be manufactured, I got knowledge.

 [0012] Compared with the above-mentioned conventionally known methods, the present invention does not require the production of difluoroacetic acid, and is one-step from 1alkoxy 1,1,2,2-tetrafluoroethane and also includes waste. The target difluoroacetate can be produced with a low and high selectivity. This is a particularly useful method for implementation on an industrial scale.

 [0013] According to the present invention, 1 alkoxy 1, 1, 2, 2-tetrafluoroethane represented by the formula [1] is reacted with an alcohol having 1 to 20 carbon atoms and a metal hydroxide or metal alkoxide. A method for producing a metal salt of difluoroacetic acid is provided.

 Detailed description

[0014] Difluoacetate, which is useful as an intermediate for readily available medicines and agrochemicals and an intermediate for functional materials, is different from the above-mentioned conventional technology, uses inexpensive materials, and is efficient and technical in one step. It became possible to manufacture. 1 Alkoxy 1, 1, 2, 2-tetrafluoroethane represented by the formula [1] as a raw material of the present invention is a known compound, and the corresponding alcohol compound (R ¹ OH) and tetrafluoroethylene Can be synthesized in the presence of a base (J. Am. Chem. Soc., 73, 1329 (1951)).

[0016] R ¹ in the 1 alkoxy 1, 1, 2, 2-tetrafluoroethane represented by the formula [1] used in this reaction represents a linear or branched alkyl group having 1 to 20 carbon atoms. 1S Among these, the usefulness of the linear or branched alkyl group strength product having 1 to 10 carbon atoms and the effect of coexistence are particularly remarkable, more preferably 1 to 6 carbon atoms. Or a linear or branched alkyl group. Specifically, 1-methoxy-1, 1, 2, 2-tetrafluoroethane, 1 ethoxy 1, 1, 2, 2-tetrafluoroethane, l- (n propoxy) 1, 1, 2 , 2-tetrafluoroethane, 1 isopropoxy 1, 1, 2, 2-tetrafluoroethane, 1- (11-butoxy) -1, 1, 2, 2-tetrafluoroethane, etc. Of these, 1-methoxy 1, 1, 2, 2-tetrafluoroethane (HFE-254pc), which is relatively easy to produce, is preferred!

 [0017] Examples of the alcohol having 1 to 20 carbon atoms used in the present invention include an alcohol represented by ROH, and R represents a linear, branched or cyclic alkyl group having 1 to 20 carbon atoms. (Wherein some or all of the hydrogen atoms may be replaced by halogen (fluorine, chlorine, bromine, iodine)) or aryl groups (where some or all of the hydrogen atoms are halogen (fluorine, Chlorine, bromine, iodine).

 [0018] Among these, the usefulness of a linear, branched or cyclic alcohol power product having 1 to 10 carbon atoms and the effect of coexistence are particularly remarkable. A linear, branched or cyclic alcohol having a number of 1 to 6.

Specifically, for example, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, n-hexanol, trifluoroethanol, hexafluoropropanol, phenol, alcohol -Mole, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tert-butanol, phenol, and more Preferably methanol, ethanol, n— Propanol, n-butanol.

 [0020] The metal hydroxide is not particularly limited as long as it is a metal hydroxide that allows the reaction to proceed efficiently. Group power consisting of potassium hydroxide, sodium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide, and calcium hydroxide. At least one selected from the group is preferred. Particularly preferred.

 [0021] The metal alkoxide is selected from the group consisting of sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium n-propoxide, potassium n-propoxide, sodium isopropoxide, potassium isopropoxide. One preferred is potassium methoxide, and particularly preferred.

[0022] The reaction of the present invention comprises diphloor metal acetate by reacting 1-alkoxy 1, 1, 2, 2-tetrafluoroethane with an alcohol having 1 to 20 carbon atoms and a metal hydroxide. Although it is a manufacturing method of salt, if a preferable combination is shown, it will be represented by the following reaction formula.

 [Chemical 2]

HCF ₂ CF ₂ OCH ₃ + CH ₃ 0H + 3K0H ~ ► CF ₂ HC00K + CH3OCH3 + 2KF + 2H ₂ 0

[0023] In this reaction, one alkoxy 1,1,2,2-tetrafluoroethane has 1 mol of alcohol per 1 mol. Alcohol is charged excessively and the cost is high. It is industrially useful to adjust the consumption of 2,2-tetrafluoroethane to increase.

 [0024] The molar ratio of 1 alkoxy 1,1,2,2-tetrafluoroethane and alcohol is 1: 0.5-1: 200, preferably 1: 1-1: 100, more preferably Can be added from 1: 1 to L: 20 and metal hydroxide and 1alkoxy 1,1,2,2-tetrafluoroethane consumed as the reaction proceeds.

[0025] In the present invention, alcohol is used as a reaction reagent, and since it can function as a solvent, it is not usually necessary to use another solvent. However, in the present invention, a solvent, The reaction rate can be increased by adding an aprotic polar solvent into the reaction system. The aprotic polar solvent used in this reaction is not particularly limited, but dimethyl sulfoxide (DMSO), dimethylacetamide (DMAC), dimethylformamide (D MF), nitromethane, acetonitrile, hexamethylphosphoric triamide (HMPA), glyme, diglyme, jetyl ether, tetrahydrofuran (THF), 1,4 dioxane, etc. , Dimethylacetamide (DMAC), dimethylformamide (DMF) and the like can be preferably used.

[0026] The amount of the solvent used is usually 0.05 to 1 times mol, preferably 0.1 to 0.3 times mol for 1 mol of 1 alkoxy 1,1,2,2-tetrafluoroethane. It is appropriately selected from the range.

 [0027] Metal hydroxide or metal alkoxide, for example, in KOH stoichiometrically added to an excess of force to react 3 moles per mole of 1 alkoxy 1, 1, 2, 2-tetrafluoroethane. If the reaction system! Since there is an increased possibility that the metal salt of difluoroacetic acid that is produced and precipitated will be precipitated together with the metal hydroxide or metal alkoxide, it becomes difficult to purify it.

 [0028] Although the reaction pressure is not particularly limited, the reaction pressure is 0.1 lMPa to l. OMPa (absolute pressure, hereinafter the same in the present specification), and preferably 0.1 lMPa to 0.6 MPa. It is. In the present invention, the target metal salt of difluoroacetate can be produced even under a mild pressure condition of 0.1 MPa to 0.6 MPa.

 [0029] Although the reaction temperature is not particularly limited, it can be carried out under relatively mild temperature conditions, and is in the range of 0 ° C to 100 ° C, preferably 20 ° C to 80 ° C, more preferably 30 °. C ~ 70 ° C is good. If the reaction temperature is too low, the reaction does not proceed, and if it is too high, the probability of side reactions increases, which is not economically preferable.

 [0030] This reaction is a semi-continuous method in which a liquid alcohol in which a metal hydroxide is saturated into 1 alkoxy 1, 1, 2, 2-tetrafluoroethane is continuously introduced, metal hydroxide. A semi-continuous system in which 1 alkoxy 1, 1, 2, 2-tetrafluoroethane is continuously introduced into liquid alcohol saturated with the product, or a batch in which all raw materials are charged into the reactor at once. It does not specifically limit, such as performing by a formula. Also, it can be produced in a continuous system in which a metal hydroxide saturated alcohol and 1-alkoxy 1,1,2,2-tetrafluoroethane are introduced into the reactor and the product is continuously withdrawn. .

[0031] The reactor is a material having heat resistance and corrosion resistance to fluorine, hydrogen fluoride, hydrogen chloride, etc. Stainless steel, Inconel, Hastelloy, etc., which are good if made with, are preferable. It can also be made from materials lined with these metals.

 [0032] In addition, 1 alkoxy 1, 1, 2, 2-tetrafluoroethane represented by the formula [1] in this reaction has a low boiling point (50 ° C or less) under normal temperature and atmospheric pressure conditions, so the reaction temperature If it is high, it may vaporize. In that case, a pressure-resistant reaction vessel is used, and the vessel can be sealed and the reaction can be carried out by the batch method described above under the conditions of the pressure described above.

 [0033] The method for the purification treatment of difluoroacetic acid metal salt is not particularly limited. The resulting difluoroacetate salt has a lower solubility in 1-alkoxy 1, 1, 2, 2-tetrafluoroethane represented by the formula [1]. In the reaction solution, it precipitates with KF as an insoluble solid mixture. The solid mixture can be easily separated by combining ordinary filtration operations. To isolate difluoroacetic acid metal salt from the solid mixture, use the difference in solubility with KF and dissolve in a good solvent such as methanol or ethanol, and add a poor solvent such as ether or hexane. It can be analyzed and separated.

[0034] The difluoroacetate can also be converted to difluoroacetic acid by reaction with an acid such as hydrochloric acid or sulfuric acid. The difluoroacetate is then converted into difluoroacetic acid and the mixture solution power is extracted with a solvent such as ether, and then It can be separated by a normal distillation operation.

 [0035] 1alkoxy 1,1,2,2-tetrafluoroethane as a starting material of the present invention can be produced by a known method. For example, a predetermined amount of methanol and a metal hydroxide are added to a pressure reactor. 1) After introducing a certain amount of tetrafluoroethylene (TFE) to form 1 alkoxy 1, 1, 2, 2-tetrafluoroethane, the reaction proceeds with the method of the present invention. It is also possible to produce a difluoroacetic acid metal salt.

 [0036] The difluoroacetic acid metal salt obtained by the present invention is a very useful compound used as an intermediate for medical and agricultural chemicals and an intermediate for functional materials.

 [0037] The obtained difluoroacetic acid metal salt can be easily converted to difluoroacetic acid by an acid hydrolysis reaction such as hydrochloric acid or sulfuric acid.

[0038] The power to specifically describe the present invention with reference to examples below. The present invention is not limited by these. Example 1

 [0039] Stainless steel lOOmllf pressure reactor with methanol 14.60g (0. 456mol), 1-methoxy

 -1, 1, 2, 2—Tetrafluoroethane (HFE—254 pc) 3.01 g (0.0228 mol), potassium hydroxide 1. l lg (0.O198 mol) were charged. The reactor was kept at 50 ° C for 8 hours (conversion rate 100%). After cooling the reactor in ice water, the deposited salt was filtered under reduced pressure and washed with ether. After vacuum drying, 0.42 g (0.0031 mol) of a mixture of potassium difluoroacetate and potassium fluoride was recovered. When the molar ratio of the recovered mixture of potassium difluoroacetate and potassium fluoride was measured by ion chromatography, it was found to be difluoroacetate-powered potassium fluoride = 1: 2 (in Example 1, it was simply Please do the refining! /, Na! /,). Example 2

 [0040] In a stainless steel 2001111 pressure reactor, 115.2 g (3.6 mol) of methanol, 1-methoxy-1,1,2,2-tetrafluoroethane (HFE—254 pc) 15. lg (0 114 mol) and 11. lg (0. 198 mol) of sodium hydroxide. The reactor was kept at 50 ° C for 16 hours (conversion rate 100%). After cooling the reactor in ice water, the precipitated salt was filtered under reduced pressure and washed with ether. After vacuum drying, 11.9 g of a mixture of potassium difluoroacetate and potassium fluoride was recovered.

 [0041] The whole mixture of potassium difluoroacetate and potassium fluoride collected in a separatory funnel was added, and diluted hydrochloric acid was added to make an acidic aqueous solution. Difluoroacetic acid was extracted from the acidic aqueous solution prepared with dimethyl ether and dried, and then the dimethyl ether was distilled off. The obtained difluoroacetic acid was neutralized with potassium hydroxide Z methanol solution, filtered, and washed with ether. After drying, 7.9 g of potassium difluoroacetate was obtained. The yield of potassium difluoroacetate based on 1-methoxy-1,1,1,2,2-tetrafluoroethane was 51.7%.

 [Comparative Example 1]

 1-Methoxy 1, 1, 2, 2-Tetrafluoroethane was used in the same manner as Example 1 except that 1-methoxyethane was used, but the reaction did not proceed at all. Acetic acid was not obtained (conversion 0%).

Claims

The scope of the claims  [1] 1-alkoxy 1, 1, 2, 2-tetrafluoroethane represented by the formula [1]  [Chemical 3] HCF ₂ CF ₂ OR ¹ (1) (Wherein R ¹ represents a linear or branched alkyl group having 1 to 20 carbon atoms) A method for producing a metal salt of difluoroacetate, comprising reacting with 1 to 20 alcohols and a metal hydroxide or metal alkoxide. [2] Metal hydroxide is potassium hydroxide, sodium hydroxide, lithium hydroxide, cesium hydroxide The production method according to claim 1, wherein the group force is selected from the group consisting of calcium hydroxide, calcium hydroxide and calcium hydroxide. [3] At least 1 in which the metal alkoxide is selected from the group consisting of sodium methoxide, potassium methoxide, sodium ethoxide, strong rhumethoxide, sodium n-propoxide, potassium n-propoxide, sodium isopropoxide, potassium isopropoxide. Claims that are species 1. The production method according to 1.  [4] The production method according to any one of claims 1 to 3, wherein the methanol power is methanol, the metal hydroxide is potassium hydroxide, and the difluoroacetic acid metal salt is potassium difluoroacetate.