WO2007072679A1

WO2007072679A1 - Process for producing 2,4-difluoronitrobenzene

Info

Publication number: WO2007072679A1
Application number: PCT/JP2006/324308
Authority: WO
Inventors: Koji Hagiya
Original assignee: Sumitomo Chemical Company, Limited
Priority date: 2005-12-20
Filing date: 2006-11-29
Publication date: 2007-06-28

Abstract

A process for producing 2,4-difluoronitrobenzene characterized by reacting 2,4-dichloronitrobenzene with potassium fluoride in the presence of a sulfone compound represented by the formula (1): R1-SO2-R2 (1) (wherein R1 and R2 are the same or different and each represents C1-3 alkyl).

Description

2, 4-Difluoronitrobenzene production method

Technical field

The present invention relates to a method for producing 2,4-difluoronitrobenzene.

Background art

book

2,4-Difluoronitrobenzene is useful as an intermediate for the synthesis of medicines and agrochemicals (see US Pat. No. 4 1 645 17). The production method thereof is in the presence of sulfolane or dimethyl sulfoxide. In addition, there is known a method of reacting 2,4-dichloronitrobenzene with potassium fluoride (see US Pat. No. 4 1 645 17 and J. Amer. Chem. So, U, 6034 (1956)). ). In addition, a method of reacting 2,4-dichloronitrile benzene and potassium fluoride in the presence of a phase transfer catalyst is also known (US Pat. No. 5,545,681, US Pat. Publication No. 2004-24238). U.S. Pat. No. 7,145,111, U.S. Pat. No. 5,502,260, JP-A-3-77850 and Tetrahedron, 51, 6363 (1995)).

Disclosure of the invention

The present invention provides the following formula (1)

R ¹ -S0 ₂ -R ² (1)

(In the formula,! 1 and ² are the same or different and each represents an alkyl group having 1 to 3 carbon atoms.)

The present invention provides a method for producing 2,4-difluoronitrobenzene, which comprises reacting 2,4-dichloronitrobenzene with potassium fluoride in the presence of a sulfone compound represented by formula (1). BEST MODE FOR CARRYING OUT THE INVENTION

As 2,4-dichloronitrobenzene, a commercially available product may be used, or one produced by a known method such as a method of nitration of m-dichlorobenzene may be used.

As the potassium fluoride, a commercially available one may be used, and for example, a potassium fluoride obtained by a known method such as a method of reacting hydroxylated hydrogen with hydrogen fluoride may be used. It is preferable to use potassium fluoride having a small particle size. It is preferable to use potassium fluoride having a low water content. Suitable potassium fluoride includes potassium fluoride produced by a spray dry method.

The amount of potassium fluoride used is usually 1 mol of 2,4-dichloronitrobenzene,

2 moles or more. The upper limit is not particularly limited, but 2 to 5 mol is preferable with respect to 1 mol of 2,4-dichloronitrobenzene from the economical viewpoint.

In the sulfone compound represented by the above formula (1) (hereinafter abbreviated as the sulfone compound (1)), R ¹ and R ² are the same or different and each represents an alkyl group having 1 to 3 carbon atoms. Examples of the alkyl group having 1 to 3 carbon atoms include linear or branched alkyl groups such as a methyl group, an ethyl group, a propyl group, and an isopyl pill group. Sulfone compound R ¹ is a methyl group (1) is preferred instrument, R ¹ is a methyl group, sulfone compounds wherein R ² is a methyl group or Echiru group (1) power beams Preferably, R ¹ is a methyl group A sulfone compound (1) in which R ² is a methyl group is more preferable.

Examples of the sulfone compound (1) include dimethylsulfone, methylethylsulfone, methylpropylsulfone, methylisopropylsulfone, jetylsulfone, dipropylsulfone and the like, and dimethylsulfone and methylethylsulfone are preferable. From the viewpoint of availability, dimethyl sulfone is more preferable.

As the sulfone compound (1), a commercially available product may be used, or a sulfone compound produced by a known method such as a method of oxidizing a corresponding sulfide compound or sulfoxide compound with an oxidizing agent such as hydrogen peroxide. Also good. The amount of the sulfone compound (1) used is usually 0.1 to 20 times the weight of 2,4-dichloronitrobenzene.

The reaction temperature is usually from 120 to 200, preferably from 150 to 200.

The reaction may be carried out without solvent or in the presence of an organic solvent inert to the reaction. When dimethyl sulfone is used as the sulfone compound (1), it is preferably carried out in the presence of an organic solvent inert to the reaction.

Examples of the organic solvent inert to the reaction include ether solvents such as dioxane and diethylene glycol dimethyl ether; amide solvents such as N, N-dimethylacetamide; aromatic carbonization such as toluene, xylene, black benzene, and benzonitrile. Hydrogen solvent; aliphatic hydrocarbon solvents such as octane and decane are listed, and aromatic hydrocarbon solvents and aliphatic hydrocarbon solvents are preferred. These organic solvents inert to the reaction may be used alone or in admixture of two or more. Of these, organic solvents that are inert to the reaction and have a boiling point of 100 to 200 ° C. are preferred.

The amount of the organic solvent inert to the reaction is usually 0.001 to 0.5 times by weight, preferably 0.001 to 0.2 times by weight, relative to the sulfone compound (1). is there.

This reaction is carried out by combining 2,4-dichloronitrobenzene, potassium fluoride, a sulfone compound (1) and, if necessary, an organic solvent inert to the reaction, and keeping the reaction temperature at a predetermined temperature while stirring. The The mixing order is not particularly limited.

In this reaction, the reaction proceeds more smoothly as the water content in the reaction system decreases. Since potassium fluoride has the property of easily absorbing moisture, it is preferable to carry out the reaction after removing the water contained in potassium fluoride in advance. As a method for removing water contained in potassium fluoride, for example, a method of mixing potassium fluoride and a sulfone compound (1) and heating to remove water; azeotrope with water such as toluene or xylene A method in which an organic solvent, potassium fluoride, and a sulfone compound (1) are mixed and heated to remove water as an azeotrope. When water contained in potassium fluoride is removed in advance, a mixture containing potassium fluoride and sulfone compound (1) obtained by removing water and 2,4-dichloronitrobenzene and The reaction is carried out by mixing.

The reaction is usually carried out under normal pressure conditions, but may be carried out under pressurized conditions. The progress of the reaction can be confirmed by ordinary analytical means such as gas chromatography or liquid chromatography.

After completion of the reaction, potassium chloride is usually precipitated in the reaction mixture. Therefore, an organic solvent insoluble in water is added to the reaction mixture as necessary, and the precipitated lithium chloride is separated by filtration, and then water is added. In addition, an organic layer containing 2,4-difluoronitrobenzene can be obtained by liquid separation treatment. By concentrating the resulting organic layer, 2,4-difluoronitrobenzene can be extracted. Without separating the precipitated potassium chloride, the reaction mixture and water may be mixed and separated. When recovering the used sulfone compound (1), it is preferable to separate the precipitated potassium chloride and then perform a liquid separation treatment. The taken 2,4-difluoronitrobenzene may be further purified by a conventional purification means such as crystallization or column chromatography.

Examples of organic solvents insoluble in water include aromatic hydrocarbon solvents such as toluene, xylene, black benzene, etc .; aliphatic hydrocarbon solvents such as pentane, hexane, heptane, etc .; halogenations such as dichloromethane, dichloromethane, black mouth form, etc. Examples include hydrocarbon solvents; ether solvents such as jetyl ether and methyl tert-butyl ether; and ester solvents such as ethyl acetate, and the amount used is not particularly limited.

In the liquid separation treatment, the sulfone compound (1) is contained in the aqueous layer separated from the organic layer containing 2,4-difluoronitrobenzene, and the aqueous layer is concentrated to remove water. Thus, the sulfone compound (1) can be recovered. The recovered sulfone compound (1) can be reused for the reaction between 2,4-dichloronitrobenzene and potassium fluoride. When potassium chloride is contained in the aqueous layer, the sulfone compound (1) is usually recovered after removing the potassium chloride by desalting or filtration. Example EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. Yield was calculated by gas chromatography internal standard method. Example 1

In a 5OmL flask equipped with a reflux condenser, potassium fluoride (sulfur dry product) 73

Omg, 5 g of dimethylsulfone and 10 g of toluene were charged. The resulting mixture was heated to an internal temperature of 13 CTC, and water in the mixture was removed as an azeotrope with toluene. Thereafter, almost all of toluene was distilled off at an internal temperature of 140, and the resulting mixture was cooled to an internal temperature of 100 ° C.

The mixture was charged with 96 Omg of 2,4-dichloronitric benzene and 30 Omg of xylene, and reacted at an internal temperature of 170 ° C for 12 hours. Dimethyl sulfone did not adhere to the reflux condenser or the inner surface of the flask.

After completion of the reaction, the reaction mixture was cooled to an internal temperature of 100, 10 g of xylene and 10 g of water were added, and liquid separation treatment was performed to obtain an organic layer containing 2,4-difluoronitrobenzene.

Yield of 2, 4-difluoronitrobenzene: 94%

Yield of monofluorochloronitrobenzene (sum of the two isomers): 5% Example 2

A 50 mL flask equipped with a reflux condenser was charged with 730 mg of the same fluorinated rhodium used in Example 1, 5 g of methylethylsulfone, and 10 g of toluene. The obtained mixture was heated to an internal temperature of 130, and water in the mixture was removed as an azeotrope with toluene. Thereafter, almost all of toluene was distilled off at an internal temperature of 14 O :, and the resulting mixture was cooled to an internal temperature of 100.

The mixture was charged with 96 mg of 2,4-dichloronitrobenzene and allowed to react at an internal temperature of 170 for 12 hours. After completion of the reaction, the reaction mixture is cooled to an internal temperature of 6 Ot :, 10 g of toluene and 10 g of water are added, liquid separation treatment is performed, and an organic layer containing 2,4-difluoronitrobenzene is added. Obtained.

Yield of 2, 4-difluoronitrobenzene: 90%

Yield of monofluorochloronitrobenzene (sum of the two isomers): 9% Example 3

A 5 OmL flask equipped with a reflux condenser was charged with 73.0 mg of potassium fluoride (powder product), 5 g of dimethylsulfone, and 1 Og of toluene. The obtained mixture was heated to an internal temperature of 1300C, and water in the mixture was removed as an azeotrope with toluene. Thereafter, almost all of toluene was distilled off at an internal temperature of 140 ° C., and the resulting mixture was cooled to an internal temperature of 100 ° C.

The mixture was charged with 96 mg of 2,4-dichloronitrobenzene and 30 Omg of xylene and allowed to react at an internal temperature of 1700C for 8 hours. Dimethyl sulfone did not adhere to the reflux condenser or the inner surface of the flask.

After completion of the reaction, the reaction mixture was cooled to an internal temperature of 100 ° C, 10 g of xylene and 10 g of water were added, and liquid separation treatment was performed to obtain an organic layer containing 2,4-difluoronitrobenzene. .

Yield of 2, 4-difluoronitrobenzene: 89%

Yield of monofluorochloronitrobenzene (sum of the two isomers): 9% Example 4

A 5 Oml flask equipped with a reflux condenser was charged with 73 Omg of potassium fluoride, 5 g of dimethylsulfone and 10 g of toluene as used in Example 1 above. The obtained mixture was heated to an internal temperature of 1300C, and water in the mixture was removed as an azeotrope with toluene. Thereafter, almost all toluene was distilled off at an internal temperature of 140 ° C, and the resulting mixture was cooled to an internal temperature of 100 ° C.

The mixture was charged with 96 Omg of 2,4-dichloronitrobenzene and reacted at an internal temperature of 1700 for 12 hours. Dimethylsulfone adhered to the reflux condenser and the inner surface of the flask.

After completion of the reaction, the reaction mixture was cooled to an internal temperature of 60, and 10 g of toluene and 10 g of water were added. In addition, liquid separation treatment was performed to obtain an organic layer containing '2,4-difluoronitrobenzene.

Yield of 2, 4-difluoronitrobenzene: 88%

Yield of monofluorochloronitrobenzene (sum of the two isomers): 5% Industrial applicability

According to the present invention, 2,4-difluoronitrobenzene useful as a synthetic intermediate for pharmaceuticals and agricultural chemicals can be produced.

Claims

The scope of the claims

1. Formula (1)

R ¹ -S0 ₂ -R ² (1)

(In the formula, R ¹ and R ² are the same or different and each represents an alkyl group having 1 to 3 carbon atoms.)

A process for producing 2,4-difluoronitrobenzene, comprising reacting 2,4-dichloronitrobenzene with potassium fluoride in the presence of a sulfone compound represented by the formula:

2. The method for producing 2,4-difluoronitrobenzene according to claim ¹ , wherein R ¹ is a methyl group.

3. The method for producing 2,4-difluoronitrobenzene according to claim ¹ , wherein R ¹ is a methyl group, and R ² is a methyl group.

4. The method for producing 2,4-difluoronitrobenzene according to claim ¹ , wherein R ¹ is a methyl group, and is an R ² force ethyl group.

5. The method for producing 2,4-difluoronitrobenzene according to claim 3, wherein the reaction is carried out in the presence of an organic solvent inert to the reaction.

6. The organic solvent inert to the reaction is at least one selected from the group consisting of ether solvents, N, N-dialkylamide solvents, aromatic hydrocarbon solvents and aliphatic hydrocarbon solvents. A process for producing 2,4-difluoronitrobenzene as described in 1.

7. The method according to claim 5, wherein the amount of the organic solvent inert to the reaction is 0.001 to 0.5 times the weight of the sulfonate compound represented by the formula (1). 4—Method for producing difluoronitrobenzene.