JP5526680B2 - Method for producing fluorine-containing carboxylic acid ester - Google Patents

Description

  The present invention relates to a method for producing a fluorinated carboxylic acid ester used as an intermediate for medical and agrochemical intermediates and functional materials, and more particularly relates to a method for producing by esterification of a fluorinated carboxylic acid halide and a metal alkoxide. .

  The production method of the fluorinated carboxylic acid ester includes an acid catalyst of a fluorinated carboxylic acid and an alcohol, a reaction with a basic catalyst, a reaction of a fluorinated carboxylic acid anhydride with an alcohol, and an ester exchange method using a fluorinated carboxylic acid ester. In addition to the above, methods such as a reaction between a fluorine-containing carboxylic acid halide and an alcohol are known.

  When a fluorine-containing carboxylic acid fluoride is used as the fluorine-containing carboxylic acid halide, direct esterification with an alcohol easily proceeds. However, in this method, equimolar hydrogen fluoride is generated as a by-product, and when hydrogen fluoride is removed by washing with water, the ester is easily hydrolyzed, and the ester and hydrogen fluoride may azeotrope in distillation separation. Furthermore, it is known that a solution containing hydrogen fluoride and alcohol corrodes a corrosion-resistant material such as stainless steel. Therefore, it is very difficult to purify a product containing hydrogen fluoride produced by this esterification reaction.

Therefore, in order to protect the reaction apparatus or avoid mixing into the product, a method for removing hydrogen fluoride or a means for substantially not generating hydrogen fluoride during the reaction is taken. (1) Triethylamine is added to a reaction system of difluoroacetic acid fluoride and ethanol (Patent Document 1), (2) a compound having an acyl fluoride group is reacted with a silane compound (Patent Document 2), (3) FOCCF ( When CF ₃ ) O (CF ₂ ) ₅ COF and propanol are monoesterified, sodium fluoride is added to the reaction system to adsorb hydrogen fluoride (Patent Document 3). Also included in the reaction solution after the reaction In order to remove hydrogen fluoride, (4) a method of washing CHF ₂ COOC ₂ H ₅ containing hydrogen fluoride with a saturated saline solution (Patent Document 4) has been reported, but hydrolysis is completely prevented. Is difficult. Unlike these, esterification with a fluorinated carboxylic acid halide has also been proposed in which an alkoxide is used instead of an alcohol in the reaction. For example, fluorine-containing carboxylic acid fluoride (5) synthesis of ester from perfluoroethercarboxylic acid fluoride and sodium phenoxide using pentafluorophenol sodium salt as a catalyst (Non-patent Document 1), and fluorine-containing carboxylic acid chloride (6) ) In esterification of perfluorocarboxylic acid chloride and phenol, the corresponding ester is synthesized using sodium hydride (NaH) having high reactivity in diethyl ether (Non-patent Document 2).

JP-A-8-92162 JP-A-8-20560 JP 2001-131119 A JP 2002-179623 A

Huaxue Xuebao, 42 (6), 541-8; 1984 Journal of Fluorine Chemistry, 108 (1), 95-109; 2001

  Hydrogen ester is by-produced during esterification of the fluorinated carboxylic acid halide and alcohol, and hydrogen fluoride is by-produced in the fluorinated carboxylic fluoride fluoride. Means are used in which an amine that forms a salt with hydrogen fluoride or sodium fluoride that adsorbs hydrogen fluoride is present. However, amine salts are difficult to decompose and regenerate hydrogen fluoride when they are separated by distillation.When NaF is used, highly corrosive NaF-HF salts are inevitably produced, and this separation is difficult. It becomes difficult. In addition, since the fluorinated ester is very hydrolyzable, a non-aqueous method that does not substantially contact with water is efficient in industrial scale implementation.

  Therefore, when producing an ester of a fluorinated carboxylic acid and an aliphatic alcohol, the fluorinated carboxylic acid ester containing no hydrogen halide such as hydrogen fluoride as a by-product is efficiently produced on an industrial scale without using a catalyst. It is an object to provide a manufacturing method.

  The present inventors examined a method using a fluorinated carboxylic acid halide and a metal alkoxide as raw materials as an esterification reaction in which hydrogen halide is not generated. When an alcohol solution of an alkali metal alkoxide is used, the reaction proceeds as expected. Although a product solution containing no hydrogen halide can be obtained, it has been found that the alcohol of the solvent may azeotrope with the fluorine-containing carboxylic acid ester of the product, resulting in a decrease in yield. Moreover, although separation of alcohol was attempted by washing with saturated saline or the like, it took time for interface separation, and during that time, the fluorinated carboxylic acid ester was hydrolyzed. Alkali metal alkoxides, which are solid at room temperature, are readily soluble in protic solvents such as alcohol, but have low solubility in aprotic solvents. Further, the reaction with fluorine-containing carboxylic acid fluorides hardly dissolves in the solvent. Since sodium fluoride is formed, a sufficient conversion rate could not be expected due to poor contact. However, when a specific solvent is used, a good reaction with the fluorinated carboxylic acid halide is achieved despite the fact that it is always in a solid dispersion state. The present inventors have found that it is possible to achieve the present invention.

  Furthermore, in the esterification reaction of a fluorine-containing carboxylic acid halide and an alcohol, it has also been found that the ratio of these raw materials or the pH at the end of the reaction has a significant effect on the reaction yield.

The present invention is as follows.
[Invention 1] General formula (1)
R _f COX (1)
(Wherein R _f represents a fluorine-containing alkyl group and X represents a halogen) and the fluorine-containing carboxylic acid halide represented by the general formula (2)
ROM (2)
(Wherein R represents a monovalent alkyl group, M represents any one of Li, Na, and K). General formula (3) comprising reacting an alkali metal alkoxide represented by the presence of a solvent. )
R _f COOR (3)
(Wherein R _f has the same meaning as in general formula (1) and R has the same meaning as in general formula (2)).
[Invention 2] Invention 1 in which the fluorinated carboxylic acid halide is difluoroacetic acid halide.
[Invention 3] Invention 2 wherein the difluoroacetic acid halide is difluoroacetic acid fluoride.
[Invention 4] 1-alkoxy-1,1,2,2-tetrafluoroethane represented by CHF ₂ CF ₂ OR ′ (R ′ represents a monovalent organic group) is heated by difluoroacetic acid fluoride. Invention 3 which is a thermal decomposition product obtained by decomposition.
[Invention 5] Any of Inventions 1 to 4, wherein the alkali metal alkoxide is a sodium alkoxide having 1 to 4 carbon atoms.
[Invention 6] Any of Inventions 1 to 5, wherein the solvent has a boiling point of 120 ° C. or higher.
[Invention 7] Any of Inventions 1 to 5, wherein the solvent is the same difluoroacetic acid ester as the product.

  According to the method of the present invention, a high-purity difluoroacetic acid ester can be produced with high yield.

The present invention relates to a general formula (1)
R _f COX (1)
(Wherein R _f represents a fluorine-containing alkyl group and X represents a halogen) and the fluorine-containing carboxylic acid halide represented by the general formula (2)
ROM (2)
(Wherein R represents a monovalent organic group and M represents any one of Li, Na, and K). General formula (3) comprising reacting a metal alkoxide represented by the presence of a solvent.
R _f COOR (3)
(In the formula, R _f is the general formula (1), and R is the same meaning as in the general formula (2)).

R _f of the fluorinated carboxylic acid halide represented by the general formula (1) is a fluorinated alkyl group, preferably having 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms. Specifically, the fluorine-containing alkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorofluoromethyl group, a chlorodifluoromethyl group, a bromodifluoromethyl group, a dibromofluoromethyl group, 2,2,2 Examples include -trifluoroethyl group, pentafluoroethyl group, 2,2,3,3,3-pentafluoropropyl group, n-hexafluoropropyl group, hexafluoroisopropyl group, and the like. Of these, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, and a 2,2,2-trifluoroethyl group are preferable, a trifluoromethyl group and a difluoromethyl group are more preferable, and a difluoromethyl group is more preferable. The halogen represented by X is fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine, more preferably fluorine.

  Specifically, difluoroacetic acid fluoride, difluoroacetic acid chloride, difluoroacetic acid bromide, difluoroacetic acid iodide, trifluoroacetic acid fluoride, trifluoroacetic acid chloride, trifluoroacetic acid bromide, trifluoroacetic acid iodide, 3,3,3-trifluoropentane Acid fluoride, 3,3,3-trifluoropentanoic acid chloride, 3,3,3-trifluoropentanoic acid bromide, 3,3,3-trifluoropentanoic acid iodide, perfluoropentanoic acid fluoride, perfluoropentanoic acid chloride Perfluoropentanoic acid bromide, perfluoropentanoic acid iodide, perfluorobutanoic acid fluoride, perfluorobutanoic acid chloride, perfluorobutanoic acid bromide, perfluorobutanoic acid Jido, perfluoropentane acid fluoride, perfluoro pentanoic acid chloride, perfluoropentane acid bromide, and the like perfluoropentane acid iodide. Particularly preferable examples of the fluorine-containing carboxylic acid halide represented by the general formula (1) include difluoroacetic acid fluoride and difluoroacetic acid chloride, and difluoroacetic acid fluoride is more preferable.

As the fluorine-containing carboxylic acid halide, those produced by a known method can be used. For example, for difluoroacetic acid fluoride, (1) a method in which difluoroacetic acid is reacted with phosphorus pentoxide, thionyl chloride, etc. and then fluorinated with a metal fluoride such as potassium fluoride, (2) expressed as CHF ₂ CF ₂ OR. 1-alkoxy-1,1,2,2-tetrafluoroethane is decomposed in the presence of sulfur trioxide and fluorosulfuric acid (non-patent document 1), (3) 1-alkoxy-1,1,2 , 2-tetrafluoroethane is reacted in the presence of a catalyst such as antimony halide or titanium halide (Patent Document 1), (4) 1-alkoxy-1,1,2,2-tetrafluoroethane is used as a catalyst. A method for producing difluoroacetic acid fluoride by thermal decomposition in the presence of (Patent Document 2) is known. It is preferable that the fluorine-containing carboxylic acid halide used in the present invention does not contain water or fluorine-containing carboxylic acid or a salt thereof. In particular, the mixing of moisture should be avoided because it contributes to the hydrolysis of the fluorinated carboxylic acid ester and as a result it becomes difficult to separate the by-produced alcohol.

The difluoroacetic acid fluoride used in the present invention may be produced by any method. For example, (1) a method in which difluoroacetic acid is reacted with phosphorus pentoxide, thionyl chloride, etc. and then fluorinated with a metal fluoride such as potassium fluoride, (2) 1-alkoxy- represented by CHF ₂ CF ₂ OR Method of decomposing 1,1,2,2-tetrafluoroethane in the presence of sulfur trioxide and fluorosulfuric acid (Non-patent Document 1), (3) 1-alkoxy-1,1,2,2-tetrafluoroethane In the presence of a catalyst such as antimony halide or titanium halide (Patent Document 1), (4) 1-alkoxy-1,1,2,2-tetrafluoroethane is thermally decomposed in the presence of a catalyst To produce difluoroacetic acid fluoride (Patent Document 2), and (5) perfluorocarboxylic acid fluoride is obtained by electrolytic fluorination of the corresponding carboxylic acid or a salt thereof. It can be obtained Te is known.

  In the method of the present invention, difluoroacetic acid fluoride obtained by thermally decomposing 1-alkoxy-1,1,2,2-tetrafluoroethane in the presence of a catalyst is preferably used. This reaction is represented by the following formula.

CHF ₂ CF ₂ OR '→ CHF ₂ COF + R'F
R of 1-alkoxy-1,1,2,2-tetrafluoroethane represented by the general formula CHF ₂ CF ₂ OR ′ (R ′ represents a monovalent organic group) which is a starting material for this reaction. 'Is a leaving group and is not particularly limited. However, it may have a branched alkyl group having 1 to 8 carbon atoms, a cycloalkyl group that may have an alkyl group as a substituent, a fluorine-containing alkyl group, an aryl group, An aralkyl group can be mentioned, and among these, an alkyl group or a fluorine-containing alkyl group is preferable, an alkyl group is more preferable, and a lower alkyl group is more preferable. In the present specification, the “alkyl group” refers to linear, branched, and cyclic unless otherwise specified. The lower alkyl group refers to an alkyl group having 1 to 4 carbon atoms.

  Examples of the alkyl group having 1 to 8 carbon atoms that may have a branch include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, s-butyl group, t-butyl group, and n-pentyl group. An isopentyl group can be given as an example. Specific examples of the lower alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an s-butyl group, and a t-butyl group. Is applicable.

  Examples of the cycloalkyl group that may have an alkyl group as a substituent include a cyclobutyl group, a cyclopentyl group, a 2-methylcyclopentyl group, a 3-methylcyclopentyl group, a 2-ethylcyclopentyl group, a 3-ethylcyclopentyl group, a cyclohexyl group, and 2 -Methylcyclohexyl group, 3-methylcyclohexyl group, 4-methylcyclohexyl group, 2-ethylcyclohexyl group, 3-ethylcyclohexyl group, 4-ethylcyclohexyl group, cycloheptyl group, 2-methylcyclohexyl group, 3-methylcyclohexane A heptyl group, 3-methylcycloheptyl group, 4-methylcycloheptyl group, etc. can be mentioned.

  As the aryl group, phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,3-dimethylphenyl group, 2,4-dimethylphenyl group, 2,5-dimethylphenyl group, 2,6-dimethylphenyl group, 3,4-dimethylphenyl group, 3,5-dimethylphenyl group, 3,6-dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, Examples include 1-naphthyl group, 2-naphthyl group and the like.

  The fluorine-containing alkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorofluoromethyl group, a chlorodifluoromethyl group, a bromofluoromethyl group, a dibromofluoromethyl group, and a 2,2,2-trifluoroethyl group. And pentafluoroethyl group, 2,2,3,3,3-pentafluoropropyl group, n-hexafluoropropyl group, hexafluoroisopropyl group and the like.

  Examples of the aralkyl group include phenethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 2,4-dimethylphenylmethyl group, 2,5 -Dimethylphenylmethyl group, 2,6-dimethylphenylmethyl group, 3,4-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 3,6-dimethylphenylmethyl group, 4-ethylphenylmethyl group, 4 Examples include-(n-propyl) methylphenylmethyl group and 4- (n-butyl) methylphenylmethyl group.

  1-alkoxy-1,1,2,2-tetrafluoroethane can be obtained by a known production method. For example, it can be synthesized by a method in which alcohol (R′OH) and tetrafluoroethylene are reacted in the presence of a base.

  Specifically, 1-methoxy-1,1,2,2-tetrafluoroethane can be synthesized by a method in which methanol and tetrafluoroethylene are reacted in the presence of potassium hydroxide (J. Am. Chem. Soc. 73, 1329 (1951)).

  Specific examples of the fluorine-containing ether that can be used in the present invention include, but are not limited to, the following. 1,1,2,2-tetrafluoro-1-methoxyethane, 1-ethoxy-1,1,2,2-tetrafluoroethane, 1- (n-propoxy) -1,1,2,2-tetrafluoro Ethane, 1-isopropoxy-1,1,2,2-tetrafluoroethane, 1- (n-butoxy) -1,1,2,2-tetrafluoroethane, 1- (s-butoxy) -1,1 , 2,2-tetrafluoroethane, 1- (t-butoxy) -1,1,2,2-tetrafluoroethane, 1-trifluoromethoxy-1,1,2,2-tetrafluoroethane, 1-difluoro Methoxy-1,1,2,2-tetrafluoroethane, 1- (2,2,2-trifluoroethoxy) -1,1,2,2-tetrafluoroethane, 1-pentafluoroethoxy-1,1, 2,2-tetrafluoro Ethane, 1- (2,2,2,3,3-pentafluoropropoxy) -1,1,2,2-tetrafluoroethane, 1-hexafluoroisopropoxy-1,1,2,2-tetrafluoroethane And so on. 1,1,2,2-tetrafluoro-1-methoxyethane, 1-ethoxy-1,1,2,2-tetrafluoroethane are particularly recommended.

The catalyst used for the thermal decomposition according to the present invention is a solid catalyst, and metal oxides and metal fluorinated oxides described in JP-A-8-92162 can be used as the catalyst. Phosphate can also be used as the catalyst. The phosphate phosphate may be supported on a carrier.
As phosphoric acid, any of orthophosphoric acid, polyphosphoric acid, and metaphosphoric acid may be used. Examples of polyphosphoric acid include pyrophosphoric acid. Phosphate is the metal salt of these phosphoric acids. Since it is easy to handle, orthophosphoric acid is preferred. Phosphate refers to a metal salt of these phosphoric acids. In this specification, an acid in which a metal is substituted with a hydrogen atom is also referred to as a metal salt.

  Although it does not specifically limit as a phosphate, It consists of hydrogen, aluminum, boron, alkaline-earth metal, titanium, zirconium, lanthanum, cerium, yttrium, rare earth metal, vanadium, niobium, chromium, manganese, iron, cobalt, nickel And at least one metal phosphate selected from the group. Preferably, the main component is aluminum phosphate, cerium phosphate, boron phosphate, titanium phosphate, zirconium phosphate, chromium phosphate, or the like. It is also preferable that the metal of a subsidiary component is included. As specific subcomponents, cerium, lanthanum, yttrium, chromium, iron, cobalt, nickel and the like are preferable, but cerium, iron and yttrium are more preferable. Of these, aluminum phosphate, cerium phosphate, and phosphates composed of these two types are more preferable.

  The method for preparing the catalyst is not particularly limited, and a commercially available phosphate may be used as it is, or a general precipitation method may be used. As a specific preparation method of the precipitation method, for example, diluted ammonia water is added dropwise to a mixed aqueous solution of metal nitrate (in the case of a plurality of raw material salts, each raw material salt solution is prepared) and phosphoric acid to adjust the pH. To allow precipitation to occur and leave for aging if necessary. Then, it is washed with water and it is confirmed that it has been sufficiently washed with the conductivity of the washing water. In some cases, alkali metal containing a portion of the slurry is measured. It is then filtered and dried. There is no particular limitation on the drying temperature. Preferably 80 to 150 degreeC is good. More preferably, it is 100 degreeC-130 degreeC. The obtained dried product is pulverized to uniform particle size, or further pulverized and molded. Thereafter, firing is performed in an air or nitrogen atmosphere at 200 ° C. to 1500 ° C. The firing is preferably performed at 400 to 1300 ° C, more preferably 500 to 900 ° C.

  Although depending on the temperature, the firing time is about 1 to 50 hours, preferably about 2 to 24 hours. Since the calcination treatment is a treatment necessary for stabilizing the phosphate, if the treatment is performed at a temperature lower than the above temperature range or the treatment time is short, the catalyst activity may not be sufficiently exhibited at the initial stage of the reaction. . In addition, it is not preferable to perform the calcination treatment at a temperature higher than the above temperature range or for a long time because not only excessive heating energy is required but also crystallization of the catalyst may occur.

The operation of adding a metal component other than the main component is preferably performed with a metal salt, and nitrates, chlorides, oxides, phosphates, and the like of the metal are preferable. Among them, nitrate is preferable because it is easy to prepare. Although there is no restriction | limiting in particular in addition amount, Generally it is 1 gram atom or less with respect to 1 gram atom of phosphorus, Preferably it is 0.5 gram atom or less. More preferably, it is 0.3 gram atom or less. The addition of these metal components may be performed at the time of catalyst preparation, or may be performed on the phosphate after the catalyst is calcined. The obtained catalyst has different physical properties depending on the type of metal salt and the preparation method and conditions. The catalyst may be used as it is, but it can also be used in a state of being supported on a carrier. As support, alumina, titania, zirconia, zirconia sulfate (ZrO (SO4))
Examples thereof include metal oxides such as metal oxides, silicon carbide, silicon nitride, activated carbon, etc., and activated carbon having a large specific surface area is particularly preferable.

  Activated carbon carrying phosphoric acid or phosphate can be prepared by immersing it in phosphoric acid and impregnating it, or drying and coating or adsorbing it by spraying. In the case of loading a compound, it can be prepared by impregnating a solution of the compound to be loaded, or drying a coating or adsorbed by spraying. In addition, a second compound is allowed to act on activated carbon impregnated with a solution of the compound, or coated or adsorbed by spraying, thereby causing a precipitation reaction or the like on the activated carbon surface to carry a compound different from the first compound. You can also. Further, the phosphate-carrying catalyst can also be prepared by carrying out the above-described phosphate preparation method in the presence of a support such as activated carbon. As an example, activated carbon supporting aluminum phosphate is shown in the examples.

  Activated carbon is made from plant-based, peat, lignite, lignite, bituminous coal, anthracite, etc. that are made from wood, charcoal, coconut husk, palm kernel charcoal, raw ash, etc. Any of petroleum type or synthetic resin type such as carbonized polyvinylidene chloride may be used. These commercially available activated carbons can be selected and used. For example, activated carbon produced from bituminous coal (BPL granular activated carbon manufactured by Toyo Calgon), coconut shell charcoal (granular white birch GX, SX, CX, XRC manufactured by Nippon Enviro Chemicals), Toyo Calgon PCB) and the like, but is not limited thereto. The shape and size are usually used in a granular form, but can be used within a normal knowledge range as long as it is suitable for a reactor such as a sphere, fiber, powder, or honeycomb.

The activated carbon used as the carrier for the thermal decomposition reaction is preferably activated carbon having a large specific surface area. The specific surface area of the activated carbon is sufficient in a range of commercially available standards, are each 400m ² / g~3000m ² / g, preferably 800m ² / g~2000m ² / g. Furthermore, when using activated carbon as a support, it is usually immersed in a basic aqueous solution such as ammonium hydroxide, sodium hydroxide, potassium hydroxide or the like for about 10 hours or longer at room temperature or when activated carbon is used as a catalyst support. It is desirable to perform pretreatment with acid such as nitric acid, hydrochloric acid, hydrofluoric acid, etc. to activate the carrier surface and remove ash in advance.

  Further, the carrier such as an oxide of the present invention may contain a metal component and an atom other than oxygen, and the other atom is preferably a fluorine atom or a chlorine atom. For example, partially fluorinated alumina, partially chlorinated alumina, partially fluorinated chlorinated alumina, partially fluorinated zirconia, partially fluorinated titania and the like may be used. The ratio of chlorine atoms and fluorine atoms in the oxide catalyst is not particularly limited.

  In the present specification and claims, unless otherwise specified, partially fluorinated or chlorinated oxides such as alumina and zirconia as described above are oxides such as “alumina” and “zirconia”. Display by name.

  These supports are preferably at least one metal oxide catalyst selected from the group consisting of alumina (Al 2 O 3), zirconia (ZrO 2), titania (TiO 2), zirconia sulfate, and partially fluorinated oxides thereof. Further, partially fluorinated alumina is more preferable in terms of reactivity and catalyst life.

These partially fluorinated oxides can be used as a support for a difluoroacetic acid fluoride synthesis catalyst, and can also be used as a catalyst. Preparation, pretreatment, use, etc. as a catalyst can be applied as described in the present specification for preparation, pretreatment, use, etc. as a carrier as it is or according to technical common sense. That is, when a metal oxide such as alumina (Al ₂ O ₃ ), zirconia (ZrO ₂ ), titania (TiO ₂ ) or the like is used as a catalyst, it can be handled in the same manner as a supported catalyst on which a metal compound or the like is supported. Good.

  The catalyst is usually used in the form of particles or granules. The diameter of the particles or the granulated body (all may be referred to as “particle diameter”) is not particularly limited, and is usually about 20 μm to 10 mm. When the catalyst contains a chlorine atom or a fluorine atom, the chlorine atom or the fluorine atom may exist only on the surface of the metal oxide.

  Before use, the catalyst is partially fluorinated by contacting with a fluorine-containing compound such as hydrogen fluoride, fluorinated hydrocarbon or fluorinated chlorinated hydrocarbon in advance to change the composition of the catalyst during the reaction, shorten the life, It is effective to prevent abnormal reactions.

  In particular, treatment with hydrogen fluoride can significantly increase the activity of the reaction. The fluorination treatment with hydrogen fluoride is preferably performed by contacting with hydrogen fluoride at least at a temperature higher than the reaction temperature of the reaction according to the present invention.

  Specifically, in the case of a phosphate simple substance, it is about 200 to 700 ° C, preferably about 250 to 600 ° C, and more preferably 300 to 550 ° C. On the other hand, in the case of a supported catalyst using an oxide or activated carbon as a carrier, the temperature is about 200 to 600 ° C, preferably about 250 to 500 ° C, more preferably 300 to 400 ° C. In any case, if the temperature is lower than 200 ° C., it takes time for the treatment, and it is not preferable to perform the treatment beyond the maximum temperature range because excessive heating energy is required. The treatment time is also related to the treatment temperature and cannot be limited, but it is about 1 hour to 10 days, preferably about 3 hours to 3 days.

  In the case of activated carbon that does not carry phosphoric acid, even if it is treated with hydrogen fluoride, it shows almost no activity. However, when activated carbon treated with phosphoric acid is treated with hydrogen fluoride, the conversion rate is 96 under the same reaction conditions. The catalyst activity was 0.1% and selectivity: 98.0%. Also from this, the effect of the hydrogen fluoride treatment can be easily seen.

  Furthermore, it is preferable to perform an activation treatment prior to the reaction. As the activation treatment, it is sufficiently dehydrated in a nitrogen stream at about 250 ° C. to 300 ° C., and an organic fluorine compound such as dichlorodifluoromethane or chlorodifluoromethane, or a gas or catalyst treatment such as hydrogen fluoride or chlorine trifluoride. It is preferable to activate with an inorganic fluorine compound showing a sufficient vapor pressure in the state. Of these, hydrogen fluoride is particularly preferred. This activation treatment is considered to generate an active catalyst containing fluorine atoms on the entire surface of the catalyst.

Further, when R ′ of 1-alkoxy-1,1,2,2-tetrafluoroethane (CHF ₂ CF ₂ OR ′), which is a raw material for thermal decomposition, is a group having 2 or more carbon atoms, R′F produced Is decomposed in the reaction region to generate hydrogen fluoride, which may have an effect of increasing the activity of the catalyst.

  The thermal decomposition reaction is recommended as a most preferable form of the gas phase flow continuous system, but is not limited thereto. The type of the reactor is preferably a fixed bed type or a fluidized bed type, and the dimensions and shape of the reactor can be appropriately changed according to the amount of the reactants and the like.

  In pyrolysis, an inert gas that is inert under the reaction conditions may be present. Examples of the inert gas include nitrogen or rare gases, and nitrogen or helium is preferable from the viewpoint of ease of handling and availability. The amount in the presence of the inert gas is not particularly limited, but if it is too much, there is a possibility that the recovery rate is lowered. Therefore, in the usual case, the raw material 1-alkoxy-1,1,2,2-tetrafluoro An amount less than the ethane feed rate is preferred.

  The reaction temperature for thermal decomposition varies depending on the type of catalyst and the raw material. Usually, it is 100-400 degreeC, about 150-350 degreeC is preferable and 180-280 degreeC is more preferable. If the reaction temperature is less than 100 ° C., the conversion tends to be low, which is not preferable. When the reaction temperature exceeds 400 ° C., severe heat resistance is required for the reaction apparatus, and excessive heating energy is required, which is not economically preferable.

  The reaction time (contact time) is usually 0.1 to 300 seconds, preferably 0.5 to 200 seconds, and more preferably 1 to 60 seconds. If the reaction time is too short, the conversion rate may be lowered. On the other hand, if the reaction time is too long, productivity is lowered, which is not preferable. The reaction pressure is not particularly limited and may be normal pressure, reduced pressure, or increased pressure. A pressure of about 0.05 to 0.5 MPa (0.5 to 5 atmospheres) is preferable, and usually a pressure in the vicinity of atmospheric pressure that facilitates operation is preferable.

  In the catalyst, coking may occur over time, and the activity of the catalyst may decrease. The catalyst having reduced activity can be easily regenerated by contacting with oxygen at 200 ° C. to 1200 ° C., preferably 400 ° C. to 800 ° C. It is convenient to perform the oxygen treatment while it is loaded in the reaction tube or in an external device. This is done by circulating oxygen there. Other gases may coexist as a method for circulating oxygen, and oxygen, air, nitrogen-diluted oxygen and the like can be used, but air or air diluted with nitrogen is economically preferable. Further, a gas having oxidizing power such as chlorine and fluorine can be used.

  In the thermal decomposition reaction, in addition to the desired difluoroacetic acid fluoride, as a by-product, a compound obtained by further decomposing alkyl fluoride (R′F) or alkyl fluoride is generated. For example, when ethyl fluoride is generated as the alkyl fluoride, ethylene and hydrogen fluoride may be formed. The crude product containing the by-product obtained by the reaction can be used as the difluoroacetic acid chloride raw material of the present invention without containing purification fluoride without purification, and is mainly obtained by removing the alkyl fluoride. The crude product can be used, and further purified and highly purified difluoroacetic acid fluoride can be used. Alternatively, these various purified gases can be cooled or compressed and stored in a pressure vessel. it can. Difluoroacetic acid fluoride can be purified by distillation.

  Next, the alkali metal alkoxide represented by the general formula (2) used in the present invention will be described. R is an alkyl group having 1 to 8 carbon atoms or a fluorine-containing alkyl group having 1 to 8 carbon atoms, and is preferably an alkyl group having 1 to 4 carbon atoms or a fluorine-containing alkyl group having 1 to 4 carbon atoms. Specifically, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an s-butyl group, a t-butyl group, an n-pentyl group, and an isopentyl group can be mentioned as examples. Specific examples of the lower alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an s-butyl group, and a t-butyl group. Group is preferred, and ethyl group is particularly preferred.

  Examples of the cycloalkyl group include a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, and the like.

  The fluorine-containing alkyl group includes a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chlorofluoromethyl group, a chlorodifluoromethyl group, a bromofluoromethyl group, a dibromofluoromethyl group, and a 2,2,2-trifluoroethyl group. And pentafluoroethyl group, 2,2,3,3,3-pentafluoropropyl group, n-hexafluoropropyl group, hexafluoroisopropyl group and the like.

  The alkali metal alkoxide is preferably an alkali metal, and the alkali metals are sodium, potassium, and lithium, and sodium is preferable because it is easily available.

  Specific examples of the alkali metal alkoxide include sodium methoxide, sodium ethoxide, sodium n-propoxide, sodium isopropoxide, sodium n-butoxide, sodium s-butoxide, sodium t-butoxide, sodium cyclohexyl, potassium methoxy Potassium ethoxide, potassium n-propoxide, potassium isopropoxide, potassium n-butoxide, potassium s-butoxide, potassium t-butoxide, potassium cyclohexyl, lithium methoxide, lithium ethoxide, lithium n-propoxide, Examples include lithium isopropoxide, lithium n-butoxide, lithium s-butoxide, lithium t-butoxide, and lithium cyclohexyl. Of these, sodium methoxide, sodium ethoxide, and sodium isopropoxide are particularly preferable.

  In the method of the present invention, an equivalent amount of the fluorinated carboxylic acid halide is used per 1 mol of the alkali metal alkoxide. Accordingly, in the case of an alkoxide of a monovalent alcohol, it is 1 to 2 mol of the fluorinated carboxylic acid halide, preferably 1 to 1.5 mol, and more preferably 1 to 1.2 mol. When the amount is 1 mol or less, the reaction solution tends to be alkaline at the end of the reaction, and the reaction yield tends to decrease. This is not preferable because use of 2 mol or more is wasteful and difficult to discard. For the same reason, in the case of an n-valent polyhydric alcohol, it is n to 2 n mol of the fluorine-containing carboxylic acid halide, preferably n to 1.5 n mol, and more preferably n to 1.2 n mol. In using the metal alkoxide used in the present invention, it is preferable to reduce the content of water, alcohol, alkali hydroxide and the like as much as possible. These may cause contamination of the product with alcohol or the like.

  As the solvent used in the present invention, a solvent inert to the reaction reagent or product is used. Alcohols may azeotrope with the produced difluoroacetic acid ester, and water is not preferred because it consumes difluoroacetic acid halide. Therefore, such a solvent is preferably an aprotic solvent, and examples thereof include aromatic solvents, chain ethers, cyclic ethers, ester solvents, amide solvents, sulfoxides, paraffins, and the like. N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAc), 1,3-dimethyl-2-imidazolidinone (DMI), N-methyl-2-pyrrolidone (MNP), diglyme, Examples include chain hydrocarbons such as triglyme, tetraglyme, polyglyme, toluene, xylene, ethylbenzene, dimethyl sulfoxide (DMSO), sulfolane, o-, m- or p-bistrifluoromethylbenzene, and decane having 8 to 20 carbon atoms. The The alkali metal alkoxide may be dissolved in the reaction system or may not be dissolved and may be in a slurry state. However, a polar solvent is preferable because the alkali metal alkoxide has high solubility and is easy to handle. Since the boiling point is not related to the reaction, a solvent having an arbitrary boiling point can be used. However, in distillation purification, a solvent whose boiling point is not close to the target difluoroacetate ester is preferable because it does not impose a load on the distillation separation. Further, a solvent having a higher boiling point than the target difluoroacetic acid ester is recommended in terms of ease of distillation, and those having a temperature of 120 ° C. or higher are preferred. There is no particular upper limit on the boiling point of the solvent, but high boiling point compounds often solidify at room temperature or have high viscosity and are inconvenient to handle. It is preferable to reduce the water content of the solvent as much as possible by adsorption or distillation with zeolite or the like. These are undesirable because they cause contamination of the product with alcohol and the like, and the purification becomes complicated.

  In addition, the same fluorine-containing carboxylic acid ester as the target compound can be used as a solvent, which is preferable. When the target compound and the solvent are used, separation of the solvent and the product becomes unnecessary, and therefore the process is simplified and it is particularly preferable. The amount of the solvent used is 2 to 20 times, preferably 3 to 10 times the mass of the alkali metal alkoxide. If it is less than 2 times, stirring is difficult and a long time is required for the reaction, and if it exceeds 20 times, operations such as recovery of the solvent become complicated.

  In addition, an inert gas can be accompanied in the reaction system. Examples of such a gas include nitrogen, argon, helium and the like, but it is usually preferable not to use them. For the reactor used in this reaction, stainless steel, Hastelloy (registered trademark), Monel (registered trademark), fluororesin, glass, or a material lined with these is used.

  The production method of the present invention is carried out at a reaction temperature of −50 to 80 ° C., preferably −20 to 50 ° C. If it is less than −50 ° C., it is not economical because extra energy is consumed for cooling, and the reaction proceeds sufficiently below 80 ° C., so there is no need to set the temperature above 80 ° C. Further, since the reaction pressure does not affect the reaction, it is not necessary to pressurize or depressurize, and it may be performed at a normal pressure of about 0.09 to 0.12 MPa. The reaction time depends on the reaction temperature, and the reaction can be completed in a very short time. Usually, the reaction time is 1 second to 50 hours, preferably 5 minutes to 10 hours, more preferably 10 minutes to 5 hours. Since the reaction rate does not improve except when it is carried out at a very low temperature even after 50 hours, it is practically unnecessary to carry out in such a time.

  As the reaction mode, any of batch type, continuous type and circulation type can be applied. The reaction may be agitated, and the agitation may be carried out by a known means such as a stirring blade, circulation, shaking or the like.

  After the reaction according to the present invention is completed, the reactor contents remaining in the reactor include a fluorinated carboxylic acid ester, an alkali halide, a solvent, an unreacted fluorinated carboxylic acid halide, and in some cases an alcohol. Impurities accompanying side reactions may be included. After separating and removing the solid alkali halide by flash distillation or the like, the reactor contents are further subjected to precision distillation using a distillation apparatus equipped with a rectifying column to obtain a high purity fluorine-containing carboxylic acid ester. It is done.

  The batch type of the production method of the present invention will be described. It will be apparent to those skilled in the art that other forms such as a continuous type can be applied by appropriately changing details based on this description and the entire description of the specification. An alkali metal alkoxide, a solvent and a fluorinated carboxylic acid halide are introduced into the reaction vessel. The order of these introductions is not limited, but an alkali metal alkoxide and a solvent are charged in the reactor in advance, and the temperature is kept below the boiling point of the fluorinated carboxylic acid halide while stirring, and the fluorinated carboxylic acid halide is gradually introduced therein. Is preferred. Since exotherm is observed at this time, it is introduced while avoiding an excessive temperature rise in the reactor. After charging a predetermined amount of the fluorinated carboxylic acid halide, the mixture is kept at about -20 to 50 ° C for about 1 to 50 hours with stirring. At this time, it is beneficial to measure the pH of the contents in order to grasp the reaction state. The PH measuring method may be an electronic PH measuring device or a simple PH test paper. If PH is on the base side, the content liquid may tar when heated by flash distillation or the like. On the other hand, by making PH acidic, the complete consumption of alcohol that is difficult to separate by distillation is confirmed. When an alkali metal alkoxide containing no moisture, alcohol, or alkali hydroxide is used, it is theoretically impossible to have an alcohol component that is difficult to separate in the system, but an industrial grade alkali metal alkoxide was used. In some cases, these may be contained. NaF produced as an by-product by the reaction also has a function of trapping HF produced by the reaction of the alcohol with the fluorine-containing carboxylic acid fluoride. PH is sufficient if it is acidic, but a pH of 6 to 3 is particularly recommended. If PH is on the base side, it can be acidified by adding an acidic substance separately. As the acidic substance, inorganic acids such as sulfuric acid, hydrochloric acid and nitric acid and organic acids such as trifluoromethanesulfonic acid can be used. It is reasonable and preferable to add the fluorine-containing carboxylic acid halide used for the reaction while confirming the pH. Thereafter, the reaction solution is appropriately subjected to flash distillation under reduced pressure to recover organic substances. The alkali halide remains as a residue. The organic substance is rectified as necessary to obtain the target fluorine-containing carboxylic acid ester as a low-boiling component. When the target product is used as a solvent, most of the organic matter flows out, but when a different solvent is used, the components mainly composed of the solvent remaining as the bottom liquid can be used again for the reaction. In that case, it can also be used after further purifying by means commonly used for solvent purification such as distillation and drying.

  EXAMPLES Hereinafter, although this invention is demonstrated using an Example, this invention is not restricted to these embodiments.

[Example 1]
A 100 ml glass three-necked flask equipped with a thermometer, blowing tube, and reflux tower was purged with nitrogen, and then sodium ethoxide (EtONa: 2.5 g) and tetraglyme (12.5 g) were charged, cooled in an ice bath, and stirred. Difluoroacetic acid fluoride (CHF ₂ COF: 3.6 g) was introduced while being bubbled through the blowing tube at a rate of about 0.7 g / min with stirring at, and the stirring was continued for 1 hour. As a result, the pH of the reaction solution was 7 showed that. The reaction solution was flashed under reduced pressure of 10 kPa to recover organic matter. The results are shown in Table 1.

[Example 2-4]
A test similar to Example 1 was conducted using diglyme (Example 2) and liquid paraffin (Example 3, N, N-dimethylacetamide (Example 4) as a solvent instead of tetraglyme. It is shown in 1.

[Example 5]
Aluminum phosphate manufactured by Aldrich was tableted into 5 mmφ × 5 mmL pellets and calcined in a nitrogen stream at 700 ° C. for 5 hours to prepare an aluminum phosphate catalyst. This was filled in 2200 cc into a large gas phase reaction tube (made of stainless steel, inner diameter 43 mmφ × 1800 mmL) having a vaporizer. The reaction tube was heated in an electric furnace provided outside while flowing 1000 cc / min of nitrogen. After the temperature of the catalyst reached 50 ° C., hydrogen fluoride (HF) was introduced through the vaporizer at a maximum rate of 6 g / min while monitoring to prevent rapid exotherm. While the HF is circulated, the temperature is slowly raised to 300 ° C., the HF supply rate is gradually increased to 12 g / min, held at 300 ° C. for 72 hours, the heater set temperature is lowered, and the internal temperature becomes 250 ° C. At that time, the flow of HF was stopped, the nitrogen flow rate was increased to 2000 cc / min and maintained for 8 hours, and then 1-methoxy-1,1,2,2-tetrafluoroethane (HFE-254pc) was added at 40 g / min. At a rate, it was introduced through a vaporizer. After 30 minutes, nitrogen was stopped and only HFE-254pc was circulated, and the pyrolysis gas was sampled in a steady state (reaction temperature: 210 ° C.) and analyzed by a gas chromatograph. CHF ₂ COF) and methyl fluoride (CH ₃ F) were contained (conversion: 99.8%).

N, N-dimethylacetamide (DMAc: 59.4 kg) and EtONa (9.0 kg) were charged into a 100 liter stainless steel reaction kettle equipped with a stirrer, and stirred while cooling from the outside with a −15 ° C. refrigerant. Here, the pyrolysis gas was bubbled. That is, 19.5 kg of HFE-254pc as a raw material was introduced into the gas phase reactor at a rate of 40 g / min, and the resulting gas was bubbled into the 100 liter Stain reactor. After completion of the introduction, cooling was stopped and stirring was continued for 12 hours at room temperature (about 25 ° C., the same in the specification). As a result, the pH of the reaction solution showed 5 or less. Flash distillation was performed at a reduced pressure of 10 kPa to obtain 37.7 kg of crude difluoroacetate (CHF ₂ COOC ₂ H ₅ ) (including DMAc solvent) (yield: 97.2%). The same experiment was repeated to obtain 37.2 kg of crude difluoroacetate (yield: 92.6%). In combination, 74.7 kg of DMAc solution (CHF ₂ COOC ₂ H ₅ content: 27.1 kg) was distilled under reduced pressure (13 kPa) in a distillation column (theoretical plate number: 10) having a can capacity of 100 liters. As a result, 25.1 kg of a fraction having a distillation temperature of 31 ° C to 33 ° C was obtained. Its ethyl difluoroacetate purity was 99.4%.

[Reference Example 1]
Methyl difluoroacetate (CHF ₂ COOCH ₃ , 10 g), which had been previously cooled in an ice bath, and ion-exchanged water (20 g) were mixed and stirred for 5 minutes while cooling in an ice bath. The aqueous phase was neutralized with an aqueous NaOH solution, and CHF ₂ COO ⁻ ions produced by hydrolysis of CHF ₂ COOCH ₃ were quantified by ion chromatography to determine the hydrolysis rate. As a result, the hydrolysis rate was 5.0%. Degree of hydrolysis, CHF ₂ COO ^- ion amount, in terms of methyl difluoroacetate weight was determined hydrolysis rate by dividing the difluoromethyl methyl acetate by weight 10g of the sample.

[Reference Example 2]
Each of CHF ₂ COOCH ₃ (20 g) cooled in an ice bath and 38% HF aqueous solution (20 g) were mixed and stirred for 5 minutes while cooling in an ice bath. The aqueous phase was neutralized with an aqueous NaOH solution, and CHF ₂ COO ⁻ ions produced by hydrolysis of CHF ₂ COOCH ₃ were quantified by ion chromatography to determine the hydrolysis rate. As a result, the hydrolysis rate was 43.0%. The hydrolysis rate was calculated by the same method as in Reference Example 1.

[Reference Example 3]
Isopropyl difluoroacetate (CHF ₂ COOCH (CH ₃ ) ₂ , 5 g), each cooled in an ice bath, and 38% HF aqueous solution (10 g) were mixed and stirred for 5 minutes while cooling in an ice bath. The aqueous phase was neutralized with an aqueous NaOH solution, and CHF ₂ COO ⁻ ions generated by hydrolysis of CHF ₂ COOCH (CH ₃ ) ₂ were quantified by ion chromatography to determine the hydrolysis rate. As a result, the hydrolysis rate was 6.9%. The hydrolysis rate was calculated by the same method as in Reference Example 1.

[Reference Example 4]
A 1000 ml glass four-necked flask equipped with a thermometer, blowing tube, and reflux tower was purged with nitrogen, charged with 20% sodium ethoxide (EtONa) / ethanol (EtOH) solution (340 g), cooled in an ice bath, and stirred. While stirring, the CHF ₂ COF (103.7 g, 1.06 mol) was introduced at a rate of about 0.7 g / min while bubbling from the blowing tube and stirring was continued for 2 hours. As a result, the pH of the reaction solution was 7 The following was shown. The contents were recovered by flash distillation under reduced pressure of 10 kPa. When the obtained organic substance was analyzed by gas chromatography (FID), ethanol: 82.6 area% and difluoroethyl acetate (CHF ₂ COOC ₂ H ₅ ): 17.4 area%. As a result of atmospheric distillation of this organic substance (170.6 g) in a distillation column having 15 theoretical plates, a main fraction (151.2 g) having a distillation temperature of 73.7 ° C. to 75.8 ° C. was obtained. The gas chromatographic composition of the obtained organic substance was ethanol: 81.0 area% and CHF ₂ COOC ₂ H ₅ : 18.8 area%, and showed an azeotropic phenomenon. This suggested that separation and purification of ethanol and CHF ₂ COOC ₂ H ₅ by distillation was substantially difficult. Incidentally, the boiling point of ethanol is 77 ° C., and the boiling point of CHF ₂ COOC ₂ H ₅ is 97 ° C.

It is useful as a method for producing difluoroacetic acid esters useful as intermediates for medicines and agricultural chemicals and functional materials.

Claims (4)

With difluoroacetic acid fluoride
General formula (2)
RONa (2)
(Wherein R represents a monovalent alkyl group having 1 to 4 carbon atoms)
Consisting of reacting in the presence of a solvent having a boiling point of 120 ° C. or higher
General formula (3)
CHF ₂ COOR (3)
(In the formula, R has the same meaning as in general formula (2).)
The manufacturing method of difluoroacetic acid ester represented by these. The process according to claim 1, wherein the solvent is N, N-dimethylacetamide. Difluoroacetic acid fluoride is obtained by thermally decomposing 1-alkoxy-1,1,2,2-tetrafluoroethane represented by CHF ₂ CF ₂ OR ′ (R ′ represents a monovalent organic group). The method for producing a difluoroacetic acid ester according to claim 1 or 2, wherein the product is a thermal decomposition product obtained. The method for producing a difluoroacetic acid ester according to any one of claims 1 to 3 , wherein the solvent is the same difluoroacetic acid ester as the product.