JPH05988A - Production of trifluoroanisole compounds - Google Patents

Abstract

PURPOSE:To simply and inexpensively produce the subject compound useful as an intermediate for medicines, agricultural chemicals, etc., by reacting a halogenated anisole compound with hydrofluoric acid in the presence of a specific fluorination catalyst. CONSTITUTION:A compound of formula I (X is C1, BR; R<1> is halogen, alkyl, alkoxy, etc.; (n) is 1, 2; (m) is 0-5; but (m+n)<=6; (p) is 0-3; (q) is 0-2; but (p+q)=3) is allowed to react with hydrofluoric acid, preferably hydrofluoric anhydride (preferably in an amount of 3.3-10 time moles per mole of the compound of formula I) in the presence of the halide compound of a metal selected from iron, aluminum, molybdenum, titanium and antimony (preferably in an amount of 0.1-10mol.% based on the compound of formula I) preferably at -10 to 50 deg.C to produce the objective compound of formula II (R<2> is the same as R<1>, but R<2> placed at the same position as R<1> is the same atom or group; and When plural R<1> exist, R<1> groups are also the same; but when fluorine is excluded from the a halogen, R<2> is F, etc.,), such as 0-chloro-alpha,alpha,alphatrifluoroanisole.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing trifluoroanisole which is useful as an intermediate for functional materials such as pharmaceutical intermediates, agricultural chemical intermediates and liquid crystals.

[0002]

2. Description of the Related Art The following methods are conventionally known as methods for producing trifluoroanisole. (1) A method of fluorinating trichloroanisole with antimony trifluoride (EP 140,783) or a method of fluorinating with trifluoroanisole (USP 4,876,376). (2) A method of simultaneously performing trichloromethylation and fluorination by reacting phenols with carbon tetrachloride in hydrofluoric acid (USP 4,157,344). (3) A method of fluorinating trichloroanisole by treating it with HF in a gas phase using an alumina catalyst (EP 196,529).

[0003]

The above-mentioned method known as a method for producing trifluoroanisole has the following problems. According to the method of EP140,783 of (1), the yield of trifluoroanisole is not sufficient. Further, in the method of USP 4,876,376, the fluorination reaction of the trichloromethoxy group is carried out in anhydrous hydrofluoric acid at 0 ° C., but when a supplementary test is conducted, only a difluoro body is formed under this reaction condition. The method (2) handles hydrofluoric acid at 170 ° C., so that it is a high-pressure reaction and is dangerous. Further, the reactor is severely corroded, and there are many industrial problems. The method (3) requires a gas phase reaction device and has many problems such as a short catalyst life.

[0004]

The present invention has been made to solve the above-mentioned problems, and halogenated anisole represented by the following chemical formula (1) is added to iron, aluminum,
By reacting with hydrofluoric acid in the presence of a fluorination catalyst composed of a halide of at least one metal selected from molybdenum, titanium and antimony, the following general conditions are used under milder reaction conditions than in conventional methods and in high yields. Formula (2)
The present invention provides a method for obtaining trifluoroanisole represented by

[0005]

[Chemical 3]

[0006]

[Chemical 4]

In the formula, X represents a chlorine atom or a bromine atom, and when X is 2 or more, X is the same atom or a combination of different atoms. R ¹ and R ² are a halogen atom, an alkyl group, a halogenated alkyl group, an alkoxy group, a formyl group, a halogenated formyl group, a nitro group, a cyano group,
R ¹ represents a carboxyl group or a carboalkoxy group,
R ^{2 at the} same position as is the same atom or group as R ¹ . When R ¹ is 2 or more, R ¹ is a combination of the same or different atoms or groups, and R ¹ is at the same position as R ^1.
2 is the same as R ¹ .

However, when R ¹ is a halogen atom other than a fluorine atom, R ^{2 at the} same position as this is the same as a fluorine atom or R ^1, and R ¹ is a halogenated formyl group other than fluorinated. If R at the same position as
² is the same as fluorinated formyl group or R ¹ . n is 1 or 2, m is an integer of 0 to 5, and m + n ≦ 6. p is an integer of 0 to 3 and q is an integer of 0 to 2, and p + q = 3.
Is.

When the number of X's in the chemical formula (1) is 2 or more, a combination of the same chlorine atom or bromine atom is preferable because it is easily available. The chemical formula (1)
As the alkyl group in (2), a lower alkyl group having 1 to 4 carbon atoms is preferable.

In the above chemical formula (1), the compound has an electron-withdrawing group such as a nitro group, a cyano group, a formyl group and a halogenated formyl group, and has a halogen atom other than a fluorine atom at the ortho or para position with respect to the group. In the case of having a halogen atom, the halogen atom is activated, and the halogen atom is easily substituted with a fluorine atom by the reaction with hydrofluoric acid.
For example, α, α, α, 4-tetrachloro-3-nitroanisole reacts with hydrofluoric acid to produce α, α, α, 4
-Becomes tetrafluoro-3-nitroanisole.

In the above chemical formula (1), a compound having a halogenated formyl group other than fluorinated is likely to be a fluorinated formyl group due to a reaction with hydrofluoric acid.

The halogenated anisole of the starting material represented by the chemical formula (1) is a relatively easily available compound, and can be synthesized by chlorinating, brominating or fluorinating the anisole.

The hydrofluoric acid used in the present invention is preferably anhydrous hydrofluoric acid. The amount of hydrofluoric acid used is 3 to 100 relative to the halogenated anisole starting material.
The molar ratio is twice, preferably 3.3 to 10 times. The amount of the fluorination catalyst used is 0.01 to 100 mol%, preferably 0.1 to 1 with respect to the halogenated anisole starting material.
It is 0 mol%. These fluorination catalysts may be added at the initial stage of the reaction, or may be added at the stage where the difluoro compound is formed during the reaction.

The reaction temperature is -50 to 150 ° C, preferably -10 to 50 ° C, and liquid phase reaction is preferred. When the reaction temperature is higher than 20 ° C., it is desirable to carry out under pressure so that the hydrofluoric acid becomes a liquid. As the reaction proceeds, hydrogen chloride is produced and the pressure rises, so it may be purged through a reflux condenser. The reaction time varies depending on the starting material, but is between a few minutes and a few hours. After completion of the reaction, the hydrofluoric acid can be recovered and reused by distillation.

The fluorination catalyst is a halide of at least one kind of metal selected from iron, aluminum, molybdenum, titanium and antimony, and a halide such as a chloride, preferably a chloride such as antimony pentachloride.

Specific examples of the compound that can be synthesized by the present invention include o-chloro-α, α, α-trifluoroanisole, m-chloro-α, α, α-trifluoroanisole and p-chloro-α, α. , Halogenated trifluoroanisole such as α-trifluoroanisole, alkylated trifluoroanisole such as 4-n-propyl-α, α, α-trifluoroanisole, 4-trifluoromethyl-α, α, α -Perfluoroalkylated trifluoroanisole such as trifluoroanisole, nitrated trifluoroanisole such as o-nitro-α, α, α-trifluoroanisole, p-nitro-α, α, α-trifluoroanisole , O-cyano-α, α, α-trifluoroanisole, p-cyano-α, α, α-trifluoroanisole, etc. Ruoroanisoru acids, 4-trifluoromethoxy benzaldehyde, 4
Examples include compounds such as trifluoromethoxybenzoyl fluoride.

[0017]

【Example】

Example 1 α, α, α-in a Hastelloy 200 ml autoclave
20 g (0.0945 mol) of trichloroanisole,
20 g (1.0 mol) of anhydrous hydrofluoric acid and 1 g (0.003 mol) of antimony pentachloride were charged, and the reaction was carried out at 15 ° C. for 6 hours with vigorous stirring. At this time, the pressure in the reactor rose to 6 kg / cm ² G.

After completion of the reaction, gas chromatography analysis revealed that the reaction rate of the raw materials was 100%, and α, α,
No products other than α-trifluoroanisole were found. After the crude product was poured into ice water, the organic layer was extracted with methylene chloride and washed with water, and then distilled to have a boiling point of 105 ° C.
There was obtained 13.3 g of α, α, α-trifluoroanisole. The yield was 86.9%.

Example 2 20 g (0.0813 mol) of α, α, α, 3-tetrachloroanisole was added to a 200 ml Hastelloy C reactor.
Charge 40 g (2.0 mol) of anhydrous hydrofluoric acid to 0
The reaction was carried out while gradually increasing the temperature from ℃ to 20 ℃. As a result of gas chromatography analysis, the product at this point was only the difluoro form.

Furthermore, when 1.2 g of antimony pentachloride was added and the reaction was carried out for 6 hours while raising the temperature from 0 ° C. to 20 ° C., the difluoro compound disappeared and 3-chloro-
α, α, α-trifluoroanisole was produced. At this time, the pressure rose to 6.2 kg / cm ² G. The same treatment as in Example 1 was carried out to obtain 13.6 g of 3-chloro-α, α, α-trifluoroanisole. Yield 85.1%
Met.

Example 3 The same reaction as in Example 2 was repeated except that α, α, α, 4-tetrachloroanisole was used as the starting material, and 4-chloro-α, α, α-trifluoroanisole 14. 4 g
Got The yield was 90.1%.

Example 4 The same reaction as in Example 2 was repeated except that 4-trichloromethoxybenzoyl chloride was used as the starting material.
Trifluoromethoxybenzoyl fluoride 12.6g
Got The yield was 83.1%.

Comparative Example 1 The same experiment as in Example 2 was conducted except that antimony pentachloride was not added. In the reaction at 20 ° C, only the difluoro body was formed, so the temperature was gradually raised and the reaction was carried out at 70 ° C for 10 hours. When the reaction solution was analyzed by gas chromatography, only 10% of the trifluoro body was formed. It was At this time, the pressure had risen to 10 kg / cm ² G.

Comparative Example 2 A 200 ml Hastelloy autoclave was charged with 43.65 g (0.24 mol) of antimony trifluoride and 3.65 g (0.0122 mol) of antimony pentachloride, and 40
Hold at 0 ° C. To this, 50 g (0.203 mol) of 4, α, α, α-tetrachloroanisole was added dropwise. The reaction temperature was raised to 110 ° C., and the reaction was carried out with vigorous stirring. Then, vacuum distillation is carried out, and 4-chloro-α, α, α-
19.15 g of trifluoroanisole was obtained. Yield 48
%Met.

[0025]

EFFECTS OF THE INVENTION The method of the present invention is superior to conventional methods in that it has no problems in working environment, has a small number of steps, is inexpensive, and has a high yield.

Claims (1)

Claims: 1. The presence of a fluorination catalyst comprising a halogenated anisole represented by the following chemical formula (1) and a halide of at least one metal selected from iron, aluminum, molybdenum, titanium and antimony. A method for producing trifluoroanisole represented by the following chemical formula (2), characterized by reacting with hydrofluoric acid below. [Chemical 1] [Chemical 2] In the formula, X represents a chlorine atom or a bromine atom, and when X is 2 or more, X is the same atom or a combination of different atoms. R ¹ and R ² represent a halogen atom, an alkyl group, a halogenated alkyl group, an alkoxy group, a formyl group, a halogenated formyl group, a nitro group, a cyano group, a carboxyl group or a carboalkoxy group, and at the same position as R ^1. Certain R ² is the same atom or group as R ¹ . R ¹ is 2
For FOB, R ¹ is a combination of same or different atoms or groups, R ² in the same position and R ¹ is the same as R ^1. However, when R ¹ is a halogen atom other than a fluorine atom, R ^{2 at the} same position as that is the same as a fluorine atom or R ¹ , and when R ¹ is a halogenated formyl group other than fluorinated, R ^{2 in the} same position as is the same as fluorinated formyl group or R ¹ . n is 1 or 2, m is an integer of 0 to 5, and m + n ≦ 6.
p is an integer of 0 to 3, q is an integer of 0 to 2, and p + q = 3.