JPS6136244A - Production of 2,4,6-trifluorobenzoic acid - Google Patents

Abstract

PURPOSE:To obtain the titled compound in high yield industrially advantageously, by hydrolyzing 3,5-dichloro-2,4,6-trifluorobenzonitrile by the use of an aqueous solution of sulfuric acid at a specific temperature, followed by reducing the reaction product with H2 and chlorinating it. CONSTITUTION:3,5-Dichloro-2,4,6-trifluorobenzonitrile is hydrolyzed in preferably 40-90wt% aqueous solution of sulfuric acid preferably at 140-200 deg.C, especially preferably at 150-170 deg.C for 1-48hr, and Cl2 in prepared 3,5-dichloro-2,4,6- trifluorobenzoic acid is reduced and dechlorinated preferably in a solvent in the presence of a hydrogenating catalyst such as Pd/C, etc. and a dehydrochlorinating agent such as KOH, etc. in an H2 atmosphere at normal pressure or by the use of an autoclave by keeping H2 pressure at <=50kg/cm<2> at 20-130 deg.C for 1- 48hr, to give the aimed compound. USE:A raw material for sensitizing agents, drugs, agricultural chemicals, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 2.4.6-trifluoro-benzoic acid. 3,5-dichloro 2,4.6-1 obtained by hydrolyzing refluorobenzonitrile
~Rifle A The chlorine atom in benzoic acid is reductively dechlorinated with hydrogen in the presence of a hydrogenation catalyst to produce 2,4.6-1~Rifle A
This invention relates to a method for producing Kuiyasuan L1 fragrant acid.

2,4.6-triful-benzoic acid is useful as a raw material for photosensitizers, medicines, agricultural chemicals, etc.

2.4.6-Trifluorobenzoic acid is a known substance. A method for synthesizing this is described, for example, in Industrial Chemistry Magazine, Vol. 73, No. 5, 1970, p. 978.

The above method involves first reacting 1.3.5-1~lifluorobenzene with 0-butyllidium in a wet melon at -60 to -70°C, and then carboxylating it using dry ice.2.4.6 -trifluorobenzoic acid.

However, in this method, the reaction is carried out at an extremely low temperature, so it is a production method that is difficult to implement on a commercial basis.

Therefore, an object of the present invention is to provide a manufacturing method that can be carried out commercially. As a result of intensive studies, the present inventors found that 3,5-dichloro-2.4.6-1 was obtained by hydrolyzing 3,5-dichloro-2,4,6-trifluorobenzonitrile. 2,4,6-trifluorobenzoic acid, which meets the above purpose, is produced by a so-called dehalogenation reaction in which the chlorine atom in benzyzoic acid is dechlorinated with hydrogen in the presence of a hydrogenation catalyst. I found out what I can do.

That is, the present invention is specified as follows.

(1) 3,5-dichloro-2,4,6-triflu obtained by hydrolyzing 3,5-dichloro-2,4,6-trifluorobenzonitrile: 4 rl in benzoic acid 2, 4.6-1 - A method for producing Riful A-benzoic acid, which comprises subjecting chlorine atoms to reductive dechlorination in the presence of a hydrogenation catalyst.

(2) In a sulfuric acid aqueous solution at a temperature range of 140 to 200°C, 3
．． The method according to (1) above, characterized in that 5-dichloro-12□4.6-trifluorobenzonitrile is hydrolyzed.

(3) The method according to (1) or (2) above, wherein the hydrogenation catalyst is palladium.

(4) In 3,5-dichloro-2,4,6-trifluor-1]benzoic acid obtained by hydrolyzing 3,5-dichloro-2.4.6-trifluorobenzonitrile, Demineralization of chlorine atoms using a hydrogenation catalyst - Reduction in the presence of a hydrogenation agent ■Desalination'? 2, 4.6- characterized by J=
Method for producing trifluorobenzoic acid.

(5) In a sulfuric acid aqueous solution at a temperature range of 140 to 200°C,
．． (4) above, characterized in that 5-dichloro-2.4.6-trifluoro[]benzonitrile is hydrolyzed.
Method described.

(6) The method according to (4) or (5), wherein the hydrogenation catalyst is palladium. (7) The dehydrochlorination agent is sodium carbonate, potassium carbonate, calcium carbonate, calcium oxide, and morenide. (II), (5) or (6), characterized in that it is at least one second selected from the group consisting of
) method described.゛Hereinafter, specific embodiments of the present invention will be explained.

3,5-dichloro-2, used as a starting material in the present invention
4,61-lifluorobenzonitrile can be prepared by a conventional method,
For example, it can be prepared by the following method.

That is, it is obtained by subjecting pentachlorobenzonitrile and potassium fluoride in a melt such as sulfolane to a halogen exchange reaction in a reaction warmer at 120 to 180°C, and then distilling the reaction product.

Alternatively, it can be synthesized by the method described in Japanese Patent Application No. 58-202590 (for example, Example 1).

A method for hydrolyzing 3,5-dichloro-12□4,6-trifluorobenzonitrile has not been proposed so far.

As a result of various studies conducted by the present inventors, it was possible to hydrolyze 3,5-dichloro-2.4.6-t-lifluorobenzonitrile by a generally known method, and 3,5-dichloro-
2,4,6-trifluorobenzoic acid can be obtained. Shika (ha) In order to produce with good yield, 140 ~
It is preferable to carry out the reaction at a temperature of 200°C (l-111).

Therefore, in the present invention, 3,5-dichloro-2,4,6-trinorolobenzoni]~lyl is dissolved in a sulfuric acid aqueous solution at 140~2
It is preferable to first obtain 3,5-difluoro-2,4,6-drifluoro[1-benzoic acid] by hydrolysis in a temperature range of 00°C.

1! I! 4()・～9() in aqueous solution
The distance between cars is amazing. Particularly preferred is 55 to 15% by weight.

The reaction temperature is preferably in the range of 140 to 200°C, and preferably 150 to 170°C.

When the reaction temperature is high, a colored tar-like compound is likely to be produced, and when the reaction temperature is low, the reaction rate decreases and productivity decreases.

Although the reaction time is not particularly limited, it is generally preferable to carry out the reaction within a range of 1 to 48 hours.

3,5-dichloro- which is the product after the completion of the hydrolysis reaction
2,4;6-trifluorobenzoic acid is molten in an aqueous sulfuric acid solution at high temperatures. However, it is solid at room temperature and has a low solubility in sulfuric acid aqueous solution, so it precipitates out. Therefore, it can be easily separated from an aqueous sulfuric acid solution by conventional methods of separating solids, such as filtration.

The obtained 3,5-dichloro-2.4.6-1~lifluorobenzoic acid was washed and then subjected to reduction JB2 chlorination.

In that case, 3,5-dichloro-2,4,6-triflu7 n
Benzoic acid may be used either dry or in a water-containing state.

In the present invention, palladium is preferred as the hydrogenation catalyst used when reducing chlorine atoms with hydrogen and chlorinating 6<2, but other hydrogenation catalysts commonly used in dehalogenation reactions, such as For example, metal catalysts such as nickel, platinum, rhodium, ruthenium, and balt can also be used. They can also be used in combination with palladium. Palladium is usually supported on a carrier such as activated carbon, silica gel, alumina, barium sulfate, or aluminum chloride. The amount of catalyst used is 3.5-dichloro-2.4.6-1 of the raw material.
- 0.0 as a catalyst component for refluoro[]acrylic acid
It is preferable to use it in a range of 0.05 to 5% by weight. More preferably, it is used in an amount of 0.05 to 1%.

Further, in the present invention, it is preferable to use a dehydrochlorination agent in combination with a hydrogenation catalyst. 112 For hydrogen chlorination agents, - Commonly used alkali metals or alkaline earths such as sodium hydroxide, potassium hydroxide, carbonate, potassium carbonate, calcium carbonate, calcium oxide, etc. Examples include oxides, hydroxides, and carbonates of similar metals.

Furthermore, organic bases such as triethylamine, tributylamine, pyridine, and lysine, ammonia, and molecular sieves can all be used.

Dehydrochlorination agent is Hara 1'! 13.5-dichloro-2,4,
It may be present in an amount of at least 2 times or more, preferably 3 to 7 times, relative to 6-trifluorobenzoic acid.

In the present invention, it is preferable to carry out the reaction in a suitable solvent, and examples of solvents include alcohols such as methanol and ethanol, glycols such as ethylene glycol and propylene glycol, dioxane, tetrahydrofuran, ■-thyl compounds such as methyl cellosolve, and acetonitrile. Examples include organic solvents such as nitriles. These organic solvents can be used alone or mixed with water.

Solvent (1) used in the present invention is the raw material 3,5-dichloro-
The amount is preferably 1 to 20 times the weight of 2,4,6-trifluorobenzoic acid.

-〇 In the present invention, the reduction reaction is carried out using hydrogen, but the reaction may be carried out in the hydrogen atmosphere at normal pressure, or may be carried out using an autoclave while maintaining the hydrogen pressure at 50 Ky/ci or less. .

The reaction suitable for the present invention can be carried out at a temperature range from room temperature to 2'00 °C, but if the reaction temperature is high, by-products such as high-boiling substances are likely to be produced, so this reaction is not suitable for the present invention. The invention is advantageously carried out in a temperature range of 20 to 130'C.

Although the reaction time is not limited, it is generally preferable to carry out the reaction within a range of 1 to 48 hours.

The product after the reaction is usually filtered to separate solids such as the catalyst, and after washing the solids, the target substance 2,
4.6-Trifluorobenzoic acid is evaporated to dryness or 2,4.6-trifluorobenzoic acid is extracted into an organic layer using an extraction solvent such as ■-tyl, methylene chloride, benzene, toluene, etc. By separating the liquids and evaporating to dryness,
He has four abilities. If necessary, this product can be further purified by methods such as recrystallization.

Hereinafter, the present invention will be explained in more detail with reference to Examples.
The present invention is limited to these examples (Example 1 [
Production of 3,5-dichloro-2.4.6-trifluorobenzoic acid] 300InI! , 200 g of 70% by weight aqueous sulfuric acid solution and 3,5-dichloro-2.4.6- in a three-necked flask.
1 Helifluorobenzonitrile 300 and 160
Heated with stirring at <RTIgt;C</RTI> for 14 hours. Next, the mixture was allowed to cool and then filtered, followed by washing to separate the solid matter. 306q of 3.5-dichloro-2°4.6-t-lifluorobankyuzoic acid was obtained by drying and drying at 60°C using a dryer. The yield C was 94.1 mol% based on the charged 3.5-dichloro-2.4.6-trifluorobenzonitrile, and the melting point of this product was 136.5°C.

Furthermore, the elemental analysis values are shown below.
Theoretical value 34,29 0.41 28.98 2
3.27 Analysis value 34.4 0.6 28,7
23.6 [Reductive dechlorination reaction of 3,5-dichloro n -2,4,6-drifluoro[]benzoic acid] 100 ml! In an autoclave made of Hasi Roy C, 35% of ethanol (] and 150% of water were used as solvents, and 5.0Q (0,020 mol) of the above-obtained 3,5-dichloro-2.4.6-t-lifluorobenzoic acid ), as a dehydrochlorination agent KO+-15,90 (IK!11185χ as 0
．． 09 mol) and a palladium-carbon catalyst as a hydrogenation catalyst (element weight ratio: pd/-5/100
) 0.3 (l), and the hydrogen pressure in the system was increased to 5 K9 /
40℃ while blowing hydrogen gas to keep it at ci G.
The mixture was heated and stirred for 5 hours.

After the reaction was completed, it was cooled to room temperature, solids such as the catalyst were removed by filtration, and then 6N sulfuric acid was added dropwise to the mother liquor so that P]=1.0 to neutralize it.2,4. An aqueous solution of 6-trifluorobenchyzoic acid was obtained. Add 150cc of ether to this solution.
was added, and 2.4.6-1-Rifle A-benzoic acid was extracted from the organic layer. This extraction operation was repeated three times, and the ether layer was dried in a hot valve.1. 2.8il of crude 2.4.6
-)-rifluorobenzoic@3.1(] was obtained. The yield was equivalent to 86.3 mol% based on the charged 3,5-dichloro-2,4,6-trifluorobenzoic acid.

This crude 2.4.6-trifluorobenzoic acid was recrystallized from bempine and had a melting point of 142-1 lr'3°C.
I got a product. The elemental analysis values for this product are shown below.

Claims (7)

[Claims] (1) Hydrolyzing 3,5-dichloro-2,4,6-trifluorobenzonitrile to replace the chlorine atom in the obtained 3,5-dichloro-2,4,6-trifluorobenzoic acid with hydrogen. A method for producing 2,4,6-trifluorobenzoic acid, which comprises carrying out reductive dechlorination in the presence of a catalyst. (2) In a sulfuric acid aqueous solution at a temperature range of 140 to 200°C, 3
, 5-dichloro-2,4,6-trifluorobenzonitrile.
1) The method described. (3) Claims in which the hydrogenation catalyst is palladium (
1) or the method described in (2). (4) Hydrolyzing 3,5-dichloro-2,4,6-trifluorobenzonitrile to replace the chlorine atom in the obtained 3,5-dichloro-2,4,6-trifluorobenzoic acid with hydrogen. A method for producing 2,4,6-trifluorobenzoic acid, which comprises carrying out reductive dechlorination in the presence of a hydrogenation catalyst and a dehydrochlorination agent. (5) In a sulfuric acid aqueous solution at a temperature range of 140 to 200°C,
, 5-dichloro-2,4,6-trifluorobenzonitrile.
4) The method described. (6) Claims in which the hydrogenation catalyst is palladium (
4) or the method described in (5). (7) Claims (4) and (5) characterized in that the dehydrochlorination agent is at least one selected from the group consisting of sodium carbonate, potassium carbonate, calcium carbonate, calcium oxide, and molecular sieve. or(
6) Method described.