JPH0717923A - Production of 3,5-difluoroaniline - Google Patents

Abstract

PURPOSE:To provide a novel method for producing 3,5-difluoroaniline from 3, 5-difluorobenzenes. CONSTITUTION:This 3,5-difluoroaniline is produced by subjecting 3,5- difluoronitrobenzenes to hydrogenation reaction with a formic acid salt in the presence of a catalyst. The method does not require complicated operation and require not handle a compound having high toxicity and an unstable compound and does not require high-temperature conditions and has hardly any subsidiary reaction, compared with reduction reaction using hydrogen.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an industrially advantageous method for producing 3,5-difluoroaniline, which is important as an intermediate for medicines and agricultural chemicals.

[0002]

2. Description of the Related Art Conventionally, as a method for producing 3,5-difluoroaniline, acetylation, nitration, hydrolysis, diazo decomposition using 2,4-difluoroaniline as a starting material,
And the way through redemption (Journal of American Chemical Society [J.Am.Chem.Soc.] (1951) 7
3, 153) is known. However, this method is not advantageous as an industrial manufacturing method because it has a long process and the raw material is expensive. In addition, 1,3,5-trichloro-2,
A method of hydrazinating and dechlorinating and reducing 4,6-trifluorobenzene (Japanese Patent Publication No. 42-13094) is known, but the toxicity of hexachlorobenzene as a raw material, the hydriodic acid used in the reduction step, and the like. There are industrial problems such as the handling and disposal of red phosphorus.

A method by amination of 1,3,5-trifluorobenzene is also known. Fluorination of 1,3,5-trichlorobenzene (Journal of Florin
Chemistry [J. Fluorine Chem.] (1991) 51, 307)
Or a method involving several steps requiring complicated operations from tetrachloroisophthalonitrile (European Patent Publication)
Manufactured by No. 0460639). But 1, 3, 5
-Since trifluorobenzene is used, it has a drawback that it is difficult to synthesize or obtain the raw material.

In addition, the reduction reaction of dihalodifluoronitrobenzenes using hydrogen as a reducing agent (Japanese Patent Laid-Open No. 4-178355) produces some inseparable impurities. have.

[0005]

SUMMARY OF THE INVENTION In the above known method,
In addition to requiring complicated operations, there is a problem in that highly toxic compounds and unstable compounds must be handled. Further, the method using a dehalogenation reaction using hydrogen has the drawbacks that high temperature conditions are required and that defluorination occurs as a side reaction. Therefore, no industrially satisfactory method is known as a method for producing 3,5-difluoroaniline.

[0006]

The present invention is the following invention which has been made to solve the above problems.

A process for producing 3,5-difluoroaniline, characterized in that at least one difluoronitrobenzene represented by the following chemical formula (1) and a formate salt are hydrogenated in the presence of a catalyst.

[0008]

[Chemical 2]

However, R ¹ , R ² and R ³ each independently represent a hydrogen atom, a chlorine atom, a bromine atom or an iodine atom.

The difluoronitrobenzenes represented by the above chemical formula (1) include 2-chloro-3,5-difluoronitrobenzene, 2,4-dichloro-3,5-difluoronitrobenzene, 2,6-dichloro-3, At least one selected from the group consisting of 5-difluoronitrobenzene and 2,4,6-trichloro-3,5-difluoronitrobenzene is preferable. The present invention can also be applied to a mixture of two or more kinds of such difluoronitrobenzenes.

The present invention is characterized in that the above-mentioned difluoronitrobenzenes and formate are hydrogenated in the presence of a hydrogenation catalyst. It is considered that formate is involved in the hydrogenation reaction by functioning as a hydrogen transfer agent.

As the formate salt in the present invention, ammonium formate, alkali metal formate salts and the like are preferable. Examples of the alkali metal formate include lithium formate, sodium formate,
Examples include potassium formate and the like. Of these, ammonium formate and sodium formate are particularly preferable as the formate salt in the present invention. Further, in the present invention, two or more formates can be used. The formate salt is preferably used in an amount of 3 to 10 equivalents based on 1 equivalent of the raw material difluoronitrobenzenes.

As the catalyst in the present invention, a known or well-known metal-supported activated carbon catalyst can be adopted.
Examples include nickel-supporting carbon, palladium-supporting carbon, platinum-supporting carbon, rhodium-supporting carbon, and ruthenium-supporting carbon. Of these, palladium-supporting carbon is particularly preferable as the hydrogenation catalyst in the present invention. The amount of metal in the metal-supported activated carbon catalyst is usually about 1 to 15% by weight, preferably 2-1.
About 0% by weight is preferable.

The amount of the catalyst used may be appropriately changed depending on the reaction conditions and the like, but in general, it is preferably about 0.1 to 50 parts by weight with respect to 100 parts by weight of the starting difluoronitrobenzenes.

The hydrogenation reaction in the present invention is usually carried out in a solvent. In this case, the solvent is preferably a protic or aprotic polar solvent. Examples of the protic polar solvent include water and alcohols such as methanol, ethanol, propanol and diethylene glycol, and examples of the aprotic solvent include dimethylformamide, dimethylacetamide, dimethylsulfoxide, and N-methylpyrrolidinone. . Of these, water, methanol and ethanol are preferred. The amount of the solvent is preferably about 2 to 50 parts by weight with respect to 1 part by weight of the raw material difluoronitrobenzenes.

The reaction conditions may be appropriately changed depending on the kinds and amounts of the raw materials and the catalyst, but in the usual case, the reaction temperature is 2
A temperature of 0 to 150 ° C., preferably 40 to 80 ° C., a reaction time of 0.5 to 24 hours, preferably 1 to 5 hours, and a reaction pressure of 0.5 to 100 atm, preferably atmospheric pressure are suitable.

In the method of the present invention, R ¹ , R ² and / or R ³ in difluoronitrobenzenes are used.
Is a chlorine atom, a bromine atom, or an iodine atom,
The R ¹ , R ² and R ³ are dehalogenated and reduced by the above reduction reaction and converted into hydrogen atoms. Therefore, R
3,5-Difluoroaniline can be obtained from difluoronitrobenzenes in which ¹ , R ² and R ³ are these halogen atoms. At least 1 of R ¹ , R ² and R ^{3 is used because} of the ease of production of the starting material, difluoronitrobenzenes.
It is preferred that these are halogen atoms, especially chlorine atoms.

The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0019]

【Example】

 [Reference Example 1] Production of 1,5-dichloro-2,4-difluorobenzene

In a 300 ml round bottom flask, 151.2 g of 1-chloro-2,4-difluorobenzene and iron chloride (I
II) 10.1 g was added and purged with a nitrogen atmosphere. While cooling with ice water, while stirring with a stirrer, chlorine gas was blown in 100 ml per minute to react for 5 hours. After completion of the reaction, the atmosphere was purged again with a nitrogen atmosphere. Then, it returned to room temperature and filtered through cerite. Distill the filtrate to give 1,5-
163.8 g of dichloro-2,4-difluorobenzene was obtained. The purity by gas chromatography analysis (hereinafter referred to as gas chromatography purity) was 98%. Boiling point 116-117 ° C (158 mmHg).

[Reference Example 2] Production of 2,6-dichloro-3,5-difluoronitrobenzene In a 500 ml round bottom flask, 1,5-dichloro-2,
4-difluorobenzene 160.6g and fuming sulfuric acid 70m
1 was put under ice cooling and purged with a nitrogen atmosphere. Fuming nitric acid (98%) 80 while stirring with a stir bar under ice water cooling
ml was added dropwise over 1.5 hours. After dropping, 50 ℃
Heated for 4 hours. The reaction solution was allowed to stand and separated into two phases for partitioning. The organic phase is distilled to give 2,6-dichloro-
130.0 g of 3,5-difluoronitrobenzene was obtained. The gas chromatography purity was 97%.
Boiling point 98-101 degreeC (9 mmHg).

Example 1 In a 50 ml round bottom flask,
0.96 g of 2,6-dichloro-3,5-difluoronitrobenzene, 4.01 g of ammonium formate, and 30 ml of methanol were added and purged with a nitrogen atmosphere. 5 wt
% Pd-supported carbon (hereinafter referred to as 5 wt% Pd-C) 0.50 g was added, and the reaction mixture was heated at 50 ° C. for 1.5 hours while stirring. After cooling to room temperature, the catalyst was filtered off using a glass fiber filter, the solvent was distilled off, the residue was adjusted to pH 10, and the residue was extracted with 10 ml of methylene chloride. After the organic phase was washed with water, the extraction solvent was distilled off, and the residue was distilled to obtain 0.42 g of 3,5-difluoroaniline. The purity by gas chromatography analysis and nuclear magnetic resonance analysis was 96%. Boiling point 62 ° C (10 mmHg).

Example 2 In a 50 ml round bottom flask,
0.96 g of 2,6-dichloro-3,5-difluoronitrobenzene, 5.11 g of sodium formate, and 30 ml of methanol were added and purged with a nitrogen atmosphere. 5 wt%
0.50 g of Pd-C was added and the reaction mixture was heated with stirring at 60 ° C. for 2 hours. After cooling to room temperature, the catalyst was filtered off using a glass fiber filter, the solvent was distilled off, the residue was adjusted to pH 10, and the residue was extracted with 10 ml of methylene chloride. After the organic phase was washed with water, the extraction solvent was distilled off, and the residue was distilled to obtain 0.30 g of 3,5-difluoroaniline. The purity determined by gas chromatography analysis and nuclear magnetic resonance analysis was 98%. Boiling point 62 to 63 ° C (10 mmHg).

[0024]

INDUSTRIAL APPLICABILITY The method of the present invention does not require complicated operations, does not need to handle highly toxic compounds or unstable compounds, and requires high temperature conditions as compared with the reduction reaction using hydrogen. The feature is that it does not occur and there are few side reactions.

Claims (3)

[Claims] 1. A method for producing 3,5-difluoroaniline, which comprises hydrogenating at least one difluoronitrobenzene represented by the following chemical formula (1) and a formate in the presence of a catalyst. [Chemical 1] However, R ¹ , R ² and R ³ are each independently a hydrogen atom,
It represents a chlorine atom, a bromine atom, or an iodine atom. 2. The difluoronitrobenzenes are 2-chloro-3,5-difluoronitrobenzene, 2,4-dichloro-3,5-difluoronitrobenzene, 2,6-dichloro-3,5-difluoronitrobenzene, and 2,2. The method according to claim 1, which is at least one selected from the group consisting of 4,6-trichloro-3,5-difluoronitrobenzene. 3. The method according to claim 1, wherein the catalyst is palladium-supporting carbon.