KR840000278B1 - Method for producing α, α, α-trifluoro-o-toluic fluoride - Google Patents

Abstract

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Description

Method for preparing α, α, α-trifluoro-o-toluic fluoride

The present invention relates to a process for the preparation of α, α, α-trifluoro-o-toluic fluoride (hereinafter abbreviated as compound I).

Chemical Abstrat 55,19888h (1961) contains 1,1,3,3-tetra chloroputaran (1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran. Heat-reacted with antimony trifluoride and treated with 20% hydrochloric acid. In the organic layer, 1,1,3,3-tetrafluorofutaran (1,1,3,3-tetrafluoro-1,3-di Hydroisobenzofuran, abbreviated hereinafter as compound II), and in the aqueous layer it is described that α, α, α-trifluoro-o-toluicamide is obtained by treating dry ammonia. The foregoing documents show that compound (I), which is a byproduct, is produced by reaction of compound (III) with antimony trifluoride.

However, the above-mentioned document does not mention the conditions for synthesizing compound (I) from compound (III) with high purity and high yield. As a result of this method performed by the present inventors, it is difficult to separate and extract compound (II) and compound (I) from the reaction product in the reaction. Was found to be an industrially advantageous method.

The inventors have found that compound (I) can be synthesized with high purity by reacting compound (III) with hydrogen fluoride.

According to the method of the present invention, in order for compound (I) to be produced in high purity, it is preferable to have many opportunities for hydrogen fluoride to come into contact with compound (II), which is regarded as an intermediate product.

This fact indicates that it is necessary to use an excessive amount of hydrogen fluoride for compound (III) at a stoichiometric ratio, for example, in the range of 10 to 20 moles of hydrogen fluoride for one compound (III). Good to do.

If the stoichiometric ratio is low, only compound (II) is produced in compound (III), and compound (I) is not obtained at all, and compound (II) and compound are used in case of using an excess of 1 to 2 activities in stoichiometric amount. When the mixture of (I) is obtained, these compounds are difficult to separate and collect by distillation.

In carrying out the method of the present invention, it is preferable to inject a compound (III) and anhydrous hydrogen fluoride into a pressure resistant corrosion resistant container and heat them together in a sealed state. In addition, the reaction can be carried out at normal pressure in the presence of a suitable fluorinated catalyst. When using a catalyst, the amount of hydrogen fluoride can be used in a stoichiometric amount or in a slight excess.

Heating temperature can be suitably selected from the range of about 50-150 degreeC, but especially near 90-120 degreeC.

The present inventors also found that compound (II) is obtained by reacting α, α, α-trichloro-o-toluic chloride (compound IV) with anhydrous hydrogen fluoride.

Therefore, in the reaction with anhydrous hydrogen fluoride, compound (III) and compound (IV) can be regarded as chemically equivalent equivalents, so the method of the present invention is known in Chemical Abstrat, 17,383 (1923) It was found that the method of the present invention can be applied to a mixture of compound (III) and compound (IV) by heating (III) at 220 ° C. for 0.5 hour to recover about 64% as compound (IV). .

Accordingly, the present invention provides a method for obtaining compound (I) in high purity by reacting a mixture of compound (III) and compound (IV) with hydrogen anhydride.

The reaction of the mixture described above with the present invention and hydrogen anhydride can be carried out according to the reaction conditions in the case of reacting the aforementioned compound (III) with anhydrous hydrogen fluoride.

The inventors have found that a mixture of compound (III) and compound (IV) is obtained by sufficiently photochlorinating o-toluic chloride (called compound VI).

Accordingly, the present invention provides a method for synthesizing compound (I) with high purity by sufficiently photochlorinating compound (VI) to allow compound (III) and compound (IV) to be formed together and then reacting with hydrogen anhydride.

Furthermore, in the Day of Chemical Society, 221,2212 (1922), the compound (VI) was chlorinated at 160-240 ° C. for about 10 hours to purify the oily substance. It is described that IV) is obtained, but in reality, the above-mentioned document that compound (IV) is an oily substance is not accurate.

The inventors found that the photochlorination reaction proceeded from compound (VI) to compound (V) relatively easily, but the progress thereafter is severe when the reaction conditions are as described in the above-mentioned literature. In addition, the decomposition of IV) also proceeds at the same time, and the contents are colored brown, and the compound (I) cannot be collected with high purity even if the resulting product is reacted with hydrogen fluoride.

Therefore, in carrying out the method of the present invention, it is necessary to perform the photochlorination reaction under relatively mild conditions and care should be taken not to reach a temperature range in which the temperature of the reaction contents promotes decomposition. In general, the reaction is preferably performed at a temperature in the vicinity of room temperature to 140 ° C, but 70 to 130 ° C is the best.

The photochlorination reaction in the present invention may be carried out in a solventless state or in a solvent such as carbon tetrachloride. As a light source, what is normally used for a photochlorination reaction is used, for example, an ultraviolet-ray, a tungsten lamp, sunlight, etc. may be used.

However, Compound (VI) is subjected to photochlorination until the compound (Ⅲ) is not detected by a suitable test method such as gas chromatography and nuclear magnetic resonance spectra under relatively mild conditions. A mixture of and compound (IV) can be obtained.

Generally, the mixture prepared as described above contains compound (III) and compound (IV) in a weight ratio of approximately 6: 4. Compound (III) is a white crystal having a melting point of 85-86 ° C. and compound (IV) is an oily substance having a boiling point of 120-130 ° C./0.5 mmHg. Therefore, when the mixture is continuously reacted with anhydrous hydrogen fluoride, compound (III) It is good to carry out on the conditions which exist in this liquid phase.

The mixture thus prepared is reacted with anhydrous hydrogen fluoride by removing dissolved chlorine by a general method. The reaction of this mixture with hydrogen fluoride is carried out under the conditions described above.

After completion of the reaction with anhydrous hydrogen fluoride, the compound (I) is extracted from the reaction contents with a suitable extraction solvent, washed with water and dried, the solvent is removed, and the pressure is distilled at atmospheric pressure. A high yield of at least 70% for (III) is obtained.

According to the method of the present invention, compound (I) is synthesized in high yield by reacting the mixture of compound (III) and compound (IV) produced by photochlorination of compound (VI) with anhydrous boron fluoride as it is. The method of the present invention is extremely valuable as a method for industrially preparing compound (I).

Example 1

화합물(Ⅲ)+화합물(Ⅳ)

화합물(Ⅰ)Compound (VI)

Compound (III) + Compound (IV)

Compound (I)

43 g (0.27 mole) of o-toluic chloride was irradiated with an ultraviolet lamp and reacted at 110-120 ° C. while passing dry chlorine. From the reaction contents, the amount necessary for gas chromatography analysis is frequently collected and compared with the standard comparison product. The peak change of α, α-dichloro-o-toluic chloride is examined and the chlorine blowing is stopped after the peak disappears. . Part of the reaction product was analyzed by gas chromatography as it is, 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran and α, α, α-trichloro-o-toluic chloride It was confirmed that the mixture was produced at a weight ratio of about 6: 4.

Quantity 67g (chlorination yield 93.4%)

Nitrogen gas was injected into the prepared mixture to dissolve dissolved chlorine gas, and then 7.6 g (0.029 mol) of the mixture was placed in Hastelloy Zeot Crab, and then sealed by adding 8.5 g (0.425 mol) of anhydrous hydrogen fluoride. The mixture is heated and stirred to the temperature of 125 ° C to 125 ° C.

Hydrogen chloride gas generated during the reaction is emitted.

After reacting for 4 hours, the mixture is cooled to room temperature, the autoclave is cooled with ice water, and the autoclave is opened.

A small amount of sodium fluoride is injected, then the contents are poured into a polyethylene flask containing ice and sodium hydrogencarbonate, methylene dichloride is injected, the reaction product is extracted with methylene dichloride, washed with water and dried over anhydrous magnesium sulfate, and then methylene di. The chloride is distilled off under atmospheric pressure. Distillation of the residue under normal pressure yields 4.5 g of α, α, α-trifluoro-o-toluic fluoride as a liquid having a boiling point of 160 ° to 162 ° C. The yield from the mixture is 80%.

Example 2

화합물(Ⅲ)+화합물(Ⅳ)Compound (VI)

Compound (III) + Compound (IV)

5 g (0.032 mol) of o-toluic chloride are dissolved in 150 ml of carbon tetrachloride, and the reaction proceeds under reflux of carbon tetrachloride while passing dry chlorine under ultraviolet lamp irradiation. From the reaction contents, the amount required for gas chromatography analysis is taken and compared with the standard product, and the peak change of α, α-dichloro-o-toluic chloride is investigated. When the peak disappears, the chlorine blowing is stopped. Part of the oily product obtained by distilling carbon tetrachloride under reduced pressure was collected, and the result of gas chromatography analysis showed 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran and α, α, α-trichloro. It was confirmed that rho-o-toluic chloride was mixed and produced in a weight ratio of about 6: 4.

Quantity 6.6 g (80% of chlorination yield)

The resulting mixture is reacted with anhydrous hydrogen fluoride by the method described in Example 1.

In other words, according to the reaction method with anhydrous hydrogen fluoride described in Example 1, when the mixture is reacted with anhydrous hydrogen fluoride, α, α, α-trifluoro-o-toluic fluoride in a yield of 75% (relative to the mixture) Obtained.

Boiling point 160˚ to 162 ℃

For reference, when the above-mentioned mixture is allowed to cool at room temperature, white crystals are precipitated, and the filtrate is recrystallized with nucleic acid to obtain 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran having a melting point of 85-86 ° C. Purity can be obtained.

H'-NMR (CDCl ₃ ): 7.72 (S) (internal standard trimethylsilane)

Further, distillation of the filtrate yields a colorless and transparent oily substance of α, α, α-trichloro-o-toluic chloride in high purity. Boiling point 120-130 ° C./0.5 mm Hg.

Example 3

화합물(Ⅰ)Compound (III)

Compound (I)

9.8 g (0.038 mole) of 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran was added to a Hasteloid autocreb and 10 g (0.5 mole) of hydrogen anhydride was added thereto to give 110 ° to 125 The mixture is heated and stirred at 0 ° C. under sealed. Hydrogen chloride gas is generated as the reaction proceeds. After reacting for 4 hours, the mixture is allowed to cool to room temperature, the autocreb is cooled with ice water, and the oatcreb is opened. A small amount of sodium hydrogen fluoride is injected and methylene dichloride is injected into a polyethylene flask containing ice and sodium hydrogen carbonate.

The reaction product is extracted with methylene dichloride, washed with water, dried over anhydrous magnesium sulfate, and the methylene dichloride is distilled off at atmospheric pressure.

Distillation of the residue at atmospheric pressure gave 5.2 g of a colorless transparent liquid. A part of the product was taken and analyzed by gas chromatography. As a result, 1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran was not identified and the desired α, α, α-trifluoro- Only o-toluic fluoride was shown.

Boiling point 160˚-162 degreeC, yield 71%.

Reference Example 1

화합물(Ⅲ)Compound (IV)

Compound (III)

40 g of α, α, α-trichloro-o-toluic chloride are heated to 110 to 130 ° C. and stirred for 7 hours under self-illumination. Subsequently, dry hydrogen chloride was introduced at the same temperature for 4 hours, and then dry chlorine gas was continuously distributed at the same temperature for 4 hours. The reaction contents were cooled to room temperature and analyzed by gas chromatography and nuclear magnetic resonance spectra.

Recovery 39.2g, Recovery 98%

According to this, the contents of the aforementioned Journal of Chemical Society are not accurate.

Reference Example 2

10 g of 1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran was placed in a Hastelloyoid oatcreb and heated and stirred in an oil bath at 120 to 150 ° C. for 5 hours. Post-treatment according to the method described in step 1 yields 9.5 g of 1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran. It was also confirmed by gas chromatography and nuclear magnetic resonance spectra analysis that no α, α, α-trifluoro-0-toluic fluoride was produced in the heated material.

This shows that heating 1,1,3,3-tetrafluoro-1,3-dihydro isobenzofuran does not change to α, α, α-trifluoro-o-toluic fluoride. have.

Claims (1)

α, α characterized by reacting a mixture of α, α, α-trichloro-o-toluic chloride with 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran with hydrogen fluoride A process for preparing α-trifluoro-o-toluic fluoride.