JPH06228043A - Production of difluoroacetic acid - Google Patents

Abstract

PURPOSE:To provide an industrially safe and simple process for producing difluoroacetic acid which is useful as a synthetic intermediate for medicines and agrochemicals. CONSTITUTION:The reaction of dichloroacetyl chloride with a secondary amine is followed by treatment of the product, N,N-disubstituted dichloroacetic amide with a fluorinating agent to give N,N-disubstituted difluoroacetic amide. The amide product is hydrolyzed to give the objective difluoroacetic acid.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel method for producing difluoroacetic acid which is useful as an intermediate for medicines and agricultural chemicals.

[0002]

2. Description of the Related Art Conventionally, the following methods have been known as methods for producing difluoroacetic acid. (1) reacting chlorotrifluoroethylene with a secondary amine to give an N, N-disubstituted chlorofluoroacetic acid amide,
This is a method of fluorinating KF to give difluoroacetic acid amide and then hydrolyzing it to synthesize difluoroacetic acid (Chem. Commun., 42 (8), 2537, 1977).

(2) A method in which tetrafluoroethylene is reacted with butylamine (primary amine) to give N-substituted difluoroacetic acid amide, which is then hydrolyzed to synthesize difluoroacetic acid (JOC, 14,747,1949, USP240).
3207).

(3) Monofluoroethylene was added to HF-HN
Fluorinated and nitrated with O ₃ to give 1,1-difluoro-2
-After converting to nitroethane (JP-A-59-155340)
JP-A-59-155341), and a method for synthesizing difluoroacetic acid by hydrolyzing this (JP-A-60-416).
34).

(4) Dichloroacetic acid methyl ester was added to KF
Fluorinating to difluoroacetic acid methyl ester (Rec.trav.chim., 65,427,1947) and then hydrolyzing this.

[0006]

In the methods (1) and (2) using chlorotrifluoroethylene or tetrafluoroethylene as a starting material, a low boiling point compound, which is difficult to handle and highly dangerous, is used as a raw material, and Since it is used at high temperature and high pressure, there is a problem in safety in operation.

In the method (3) using monofluoroethylene as a starting material, there is a problem in the apparatus because a highly corrosive raw material is used.

In the method (4) of fluorinating dichloroacetic acid ester with KF, the yield of difluoroacetic acid is as low as about 18% due to poor stability of the ester during the fluorination reaction.

[0009]

The present invention has been made to solve the problems of the handling of starting materials, reactors, and yields, which the prior art had, and was designed to be industrially safe and convenient. A method for producing acetic acid is provided.

That is, in the present invention, dichloroacetic acid chloride is reacted with a secondary amine to give N, N-disubstituted dichloroacetic acid amide, and the N, N-disubstituted dichloroacetic acid amide is reacted with a fluorinating agent to give N, N-disubstituted dichloroacetic acid amide. A method for producing difluoroacetic acid, which comprises hydrolyzing the N, N-disubstituted difluoroacetic acid amide after the N-disubstituted difluoroacetic acid amide is prepared.

The starting material of the present invention, dichloroacetic acid chloride, is a commercially available and easily available compound.

The first-stage amidation reaction can be carried out by adding dichloroacetic acid chloride dropwise to the secondary amine in the absence of solvent or a solvent inert to the reaction. Examples of suitable secondary amines include compounds represented by the general formula NHR ¹ R ^2. R ¹ and R ² are preferably alkyl groups having 1 to 10 carbon atoms, and R ¹ and R ² are ring groups. It may be formed.

The reaction temperature is -20 to 100 ° C, preferably 0 to 50 ° C. The amount of the secondary amine used is 0.5 to 10 mol, preferably 1.5 to 5 mol, based on 1 mol of dichloroacetic acid chloride. After the reaction, by-products can be removed by filtration, and the N, N-disubstituted dichloroacetic acid amide can be isolated by distillation. When a suitable secondary amine is used, N, N represented by the general formula CHCl ₂ CONR ¹ R ² is used.
A disubstituted dichloroacetic acid amide is obtained. R ¹ and R ² correspond to R ¹ and R ² of the secondary amine used.

The second stage fluorination reaction can be carried out by reacting with a fluorinating agent in the absence of solvent or a polar solvent. As fluorinating agents, NaF, KF, RbF, C
Alkali metal fluorides such as sF are preferable, and spray-dried potassium fluoride is particularly preferable. The amount of the alkali metal fluoride used is 1 to 10 mol, preferably 1.2 to 5.
It is 0 mol.

During the fluorination, a fluorination catalyst may be added as a reaction accelerator. Specific examples of such a fluorination catalyst include quaternary ammonium salts such as tetramethylammonium chloride and tetrabutylammonium bromide, N-neopentyl-4- (N, N-dimethylamino) -pyridinium chloride, N- (2 Examples thereof include pyridinium salts such as -ethyl-hexyl) -4- (N, N-dimethylamino) -pyridinium chloride, and quaternary phosphonium salts such as tetrabutylphosphonium bromide and tetraphenylphosphonium bromide. The addition amount of the fluorination catalyst is 0.005 to 0.5 part by weight, preferably 0.01 to 0.1 part by weight, relative to 1 part by weight of the N, N-disubstituted dichloroacetic acid amide. By adding the fluorination catalyst, the reaction time can be shortened and the reaction temperature can be lowered without lowering the yield.

As the polar solvent, N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, dimethyl sulfone, sulfolane, hexamethylphosphortriamide, N-methyl-2-pyrrolidone,
Acetonitrile, benzonitrile, dioxane, diglyme, tetraglyme, ethylene glycol, diethylene glycol, propylene glycol and the like can be used. The amount used is N, N-disubstituted dichloroacetic acid amide 1
1.0 to 10 parts by weight, preferably 1.0
~ 5 parts by weight.

The reaction temperature of the fluorination reaction is 100 to 300.
C., preferably 150 to 200.degree. The reaction temperature can be lowered by adding a fluorination catalyst. The reaction pressure may be any of normal pressure, spontaneous pressure and pressurization, or can be carried out under pressurization with an inert gas such as nitrogen gas. The reaction time is about 5 to 20 hours, varying depending on the reaction temperature and the amount of the catalyst added.

The N, N-disubstituted difluoroacetic acid amide can be obtained by the fluorination reaction. When a suitable secondary amine is used, an N, N-disubstituted difluoroacetic acid amide represented by the general formula CHF ₂ CONR ¹ R ² is obtained. R ¹ and R ² correspond to R ¹ and R ² of the secondary amine used.

The hydrolysis reaction of the above N, N-disubstituted difluoroacetic acid amide can be easily carried out by refluxing in an alkaline aqueous solution and subsequent acidification to obtain the desired difluoroacetic acid. Hereinafter, examples of the present invention will be described more specifically.

[0020]

Example 1 A 1000 ml glass reactor equipped with a reflux condenser, dropping funnel and stirrer was charged with diethylamine 1
Charge 50 g (2.05 mol) and 400 g of toluene,
With vigorous stirring, 100 g of dichloroacetic acid chloride was gradually added dropwise at 10 ° C. While paying attention to heat generation, the solution was added dropwise over about 2 hours. After the reaction, by-products were removed by filtration and then distilled to obtain 111 g of N, N-diethyldichloroacetamide (yield 89%).

Example 2 In a 500 ml glass reactor equipped with a reflux condenser and a stirrer, the N, obtained in Example 1,
N-diethyldichloroacetamide (100 g), spray-dried potassium fluoride (78.9 g) and diethylene glycol (250 g) were charged, and while vigorously stirring, 15
The reaction was carried out at 0 ° C for 7 hours. After the reaction, analysis by gas chromatography was performed, and as a result, 61.6 g (yield 75%) of N, N-diethyldifluoroacetamide was obtained.

[Example 3] A fluorination reaction was carried out in the same manner as in Example 2 except that 5 g of tetrabutylammonium bromide was added as a fluorination catalyst. After reaction at 120 ° C. for 5 hours, analysis by gas chromatography revealed that N, N-diethyldifluoroacetamide 64.
1 g (yield 78%) was obtained.

Example 4 A 200 ml glass reactor was charged with 50 g of the N, N-diethyldifluoroacetamide obtained in Example 2 or Example 3 and 260 g of a 10% sodium hydroxide aqueous solution, and the mixture was reacted under reflux for 4 hours. As a result of analysis by gas chromatography, the raw material had disappeared. Aqueous hydrochloric acid solution was added dropwise to this to acidify it to give difluoroacetic acid, which was then separated by distillation. 132-135 under normal pressure
Difluoroacetic acid containing 10% of water as a fraction at ℃ 3
2.5 g (yield 92%) was obtained.

[0024]

INDUSTRIAL APPLICABILITY According to the present invention, difluoroacetic acid can be obtained industrially safely and simply without problems such as handling of the starting material, reaction apparatus and yield, as compared with the conventional method.

Claims (3)

[Claims] 1. A dichloroacetic acid chloride is reacted with a secondary amine to give an N, N-disubstituted dichloroacetic acid amide, which is
Difluoroacetic acid characterized by reacting N-disubstituted dichloroacetic acid amide with a fluorinating agent to give N, N-disubstituted difluoroacetic acid amide, and then hydrolyzing said N, N-disubstituted difluoroacetic acid amide. Manufacturing method. 2. The method according to claim 1, wherein the fluorinating agent is an alkali metal fluoride. 3. The method according to claim 1, wherein the fluorination reaction is carried out in the presence of a fluorination catalyst.