JPS6143344B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an industrially advantageous method for producing 3-trifluoromethylpyridine by reducing specific chloro3-trifluoromethylpyridines.

3-Trifluoromethylpyridine is a substance useful as a raw material in various organic synthetic chemical industries, and has traditionally been produced by reacting nicotinic acid and sulfur tetrafluoride in the presence of hydrogen fluoride. Since the yield is low and sulfur tetrafluoride is difficult to handle, it cannot be said to be suitable for industrial use.

The present inventors have established an industrially advantageous method for producing chloro-3-trichloromethylpyridines by chlorinating β-picoline, and have therefore reduced chloro-3-trichloromethylpyridines to produce 3-trichloromethylpyridine. An attempt was made to produce 3-trifluoromethylpyridine by fluorinating it. However, this attempt was found to be inappropriate because chloro3-trichloromethylpyridines are decomposed by reduction treatment. Further investigation revealed that (i) the chlorine atoms at the 2nd and 6th positions of the middle pyridine ring of chloro3-trifluoromethylpyridines are highly reactive; (ii)
The fact that 3-trifluoromethylpyridine can be obtained satisfactorily by fluorinating chloro3-trichloromethylpyridines to produce chloro3-trifluoromethylpyridines and reducing this; and (iii) using β-picoline as a raw material. The present invention was completed based on the discovery that the industrial significance is greater when the method is used.

The first invention of the present application provides 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethylpyridine, and 2,6-dichloro-3
- A method for producing 3-trifluoromethylpyridine by reducing one or more chloro3-trifluoromethylpyridines selected from the group consisting of trifluoromethylpyridine, and
The second invention of the present application is to simultaneously or sequentially chlorinate and fluorinate β-picoline in the gas phase in the presence of an inert diluent prior to the reduction of the chloro3-trifluoromethylpyridines. Chloro 3-
This is a method of producing trifluoromethylpyridines and filtering them to produce 3-trifluoromethylpyridine.

In carrying out the present invention, β-picoline is simultaneously brought into contact with chlorine and anhydrous hydrogen fluoride in a gaseous state in the presence of an inert diluent to react to directly produce chloro-3-trifluoromethylpyridines. Alternatively, β-picoline is reacted with chlorine to produce chloro3-trichloromethylpyridines, and then this chloro3-trichloromethylpyridine is reacted with anhydrous hydrogen fluoride to produce chloro3-trichloromethylpyridines.
-Methods for producing trifluoromethylpyridines can be mentioned. Examples of inert diluents include carbon tetrachloride, chloroform, methylene chloride, trichlorethylene, tetrachloroethylene, F-112
Organic solvents such as hydrogen halides such as (CFcl ₂ / CFcl ₂ ) and F-113 (CF ₂ cl / CFcl ₂ ), and inert gases such as nitrogen and helium can be used. It has the function of suppressing carbonization, generation of tar-like byproducts, etc.

When producing chloro-3-trifluoromethylpyridines directly from β-picoline, the raw materials of β-picoline, chlorine, anhydrous hydrogen fluoride, and an inert diluent can be supplied separately to the reactor, or they can be mixed together. It can also be supplied after
Once preheated to 200-300°C, it is introduced into the reactor. For example, β-picoline is supplied after being vaporized as it is, or once dissolved in an organic solvent and then vaporized, and anhydrous hydrogen fluoride is supplied after being vaporized as is. Furthermore, when these substances are supplied, they are mixed appropriately with chlorine or an inert diluent before being subjected to the reaction.

The amounts of chlorine, anhydrous hydrogen fluoride, and inert diluents cannot be absolutely specified due to differences in other reaction conditions, but are generally 2 to 15 mol, 2 to 60 mol, and 2 to 60 mol, respectively, per 1 mol of β-picoline. ~70 mol,
The reaction temperature is typically 300 DEG to 600 DEG C., and the residence time of the reaction mixture in the reaction zone is typically 3 to 60 seconds. Furthermore, this reaction can also be carried out in the presence of a filler such as activated carbon or alumina;
Its existence is not necessarily essential. In industrial implementation, these substances can be present in a reactor as a fixed bed or a fluidized bed to improve reaction efficiency.

Usually, the reactor contains fluorinated products mainly composed of chloro3-trifluoromethylpyridines, unreacted hydrogen fluoride and chlorine, intermediate products, by-product hydrogen chloride, and an inert diluent. Gaseous substances are discharged, but generally 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethylpyridine, 2,6-dichloro-3-trifluoro For example, a liquid substance of chloro3-trifluoromethylpyridine containing one or more types of methylpyridine is
Obtained with a production rate of 55% or more.

In addition, when producing chloro-3-trifluoromethylpyridines from β-picoline via chloro-3-trichloromethylpyridines, there is a case where chloro-3-trifluoromethylpyridines are produced directly from β-picoline as described above. It can be implemented in almost the same way.

In general, β-picoline and chlorine raw materials and inert diluents are used separately or in a mixed state at a concentration of 200 to 300
It is preheated to ℃ before being fed to the reactor. The amounts of chlorine and inert diluent used are generally 4-8 mol and 3-70 mol, respectively, per mol of β-picoline, the reaction temperature is usually 300-500°C, and the residence time of the reaction mixture in the reaction zone is also 1-8 mol. It is 60 seconds. The exhaust gas from the reactor contains chloro3-trichloro containing 2-chloro-3-trichloromethylpyridine, 2-chloro-5-trichloromethylpyridine, 2,6-dichloro-3-trichloromethylpyridine, or mixtures thereof. It contains chlorinated products mainly composed of methylpyridines, by-product hydrogen chloride, inert diluents, etc., and is appropriately cooled and condensed to be collected as a liquid, and purified by ordinary purification means, e.g. % or more of chloro3-trichloromethylpyridines. Furthermore, this Chloro 3
-Trichloromethylpyridine is usually preheated to 250-300°C and then fed to the reactor, either separately or in a mixed state, with the raw materials anhydrous hydrogen fluoride and an inert diluent. Furthermore, if this reaction is carried out in the presence of activated carbon or in the presence of a mixed catalyst consisting of a metal fluoride of chromium, iron or nickel and, if necessary, an ammonium fluoride compound, the production rate of chloro3-trifluoromethylpyridines can be reduced. can be improved. Anhydrous hydrogen fluoride and an inert diluent are generally used from 3 to 15 mol and from 1 to 10 mol, respectively, per mole of chloro-3-trichloromethylpyridine, and the reaction temperature is usually from 200 to 700°C, and the reaction mixture remains in the reaction zone. The time is also 1 to 100 seconds. The exhaust gas from the reactor contains one or more of 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethylpyridine, and 2,6-dichloro-3-trifluoromethylpyridine. It contains fluorinated products mainly composed of chloro3-trifluoromethylpyridines, by-product hydrogen chloride, inert diluent, etc., and is cooled, condensed, and purified to a production rate of 80% or more. chloro3-trifluoromethylpyridines are obtained as a liquid substance.

When the aforementioned chloro-3-trifluoromethylpyridines are reduced, chlorine in the pyridine ring is easily removed and replaced with hydrogen to produce 3-trifluoromethylpyridine. For this reduction reaction, ordinary means for a substitution reaction between a halogen atom and hydrogen can be applied. Examples include a method of reacting with acetic acid, hydrochloric acid, sulfuric acid, sodium hydroxide, etc. in the presence of zinc or iron powder, and a method of reacting with hydrogen gas in the presence of a platinum, nickel, or palladium catalyst.

These reactions are generally carried out at temperatures below 200°C.
In addition, water, alcohols, fatty acids, ethers,
It is common to use solvents such as polar aprotic solvents. Furthermore, a method of reacting with hydrogen gas at 200 to 400° C. in the presence of a copper or silver-based catalyst in a gaseous state is also exemplified. In these reactions, the trifluoromethyl group of chloro3-trifluoromethylpyridine is not decomposed and only the chlorine atom selectively replaces the hydrogen atom, making it possible to produce 3-trifluoromethylpyridine at a high rate. can. Therefore, if this product is subjected to conventional separation and purification methods such as filtration, extraction, and distillation, highly pure 3-trifluoromethylpyridine can be produced in high yield.

Example 1 2-chloro-5-trifluoromethylpyridine
Dissolve 91g in 200ml of acetic acid and heat to 90-100℃
65g of zinc powder was added over 2 hours at 110℃.
The mixture was reacted under reflux for about 1 hour. The reaction product was allowed to cool and filtered to remove solid matter, then poured into water, extracted with methylene chloride, washed with water, dried over sodium sulfate, and filtered. Distill the methylene chloride to a boiling point of 115℃
7 g of 3-trifluoromethylpyridine was obtained.

Example 2 Using a glass reactor for catalytic reduction, 4.3 g of 2,6-dichloro-3-trifluoromethylpyridine
and 6 g of triethylamine were dissolved in 100 ml of methanol, and a palladium carbon catalyst (Pd content: 5
%) 0.2g was added. After replacing the gas in the reactor with hydrogen gas, the reactor was pressurized with hydrogen at 3 kg/cm ² and catalytic reduction was carried out at room temperature for 3 hours. After the reaction was completed, the catalyst was separated and distilled to obtain 2.5 g of 3-trifluoromethylpyridine.

Example 3 Using an autoclave reactor, put 25.9 g of 2,6-dichloro-3-trifluoromethylpyridine, 27.9 g of triethylamine, 30 ml of water, and 0.13 g of palladium on carbon catalyst (Pd content 2%) into a 200 ml container, and Introduce hydrogen into the tank and increase the hydrogen pressure to 20Kg/
Catalytic reduction was carried out at a reaction temperature of 75° C. for 45 minutes while maintaining the temperature at cm ² . After the reaction was completed, the catalyst was separated, a small amount of dilute hydrochloric acid was added to the liquid to adjust the pH to 3.5, and the oil layer was separated and distilled to obtain 16.8 g of 3-trifluoromethylpyridine with a purity of over 99%. The aqueous layer was made alkaline with a small amount of dilute caustic soda aqueous solution, and 27.5 g of triethylamine was recovered.

Example 4 (1) Chlorination of β-picoline Using a glass reaction tube with a diameter of 4 cm and a length of 70 cm, 9.4 ml of a solution of β-picoline and carbon tetrachloride in a molar ratio of 1:10 and 1020 ml of nitrogen per minute. Then, 1020 ml of chlorine gas was supplied through a preheating tube for 60 minutes, and a gas phase reaction was carried out at 400° C. while controlling the temperature. After condensing the exhaust gas from the reaction tube, washing and drying, the solvent was distilled off and 56% of 2-chloro-5-trichloromethylpyridine, 14% of 2-chloro-3-trichloromethylpyridine and 2,6-dichloro 113 g of an oil containing 17% of -3-trichloromethylpyridine was obtained.

(2) Fluorination of chloro3-trichloromethylpyridines Inner diameter 4.2 cm and length filled with 100 g of activated carbon
Using a 125cm stainless steel reaction tube, 170g of chloro3-trichloromethylpyridine was produced per minute.
288 g of carbon tetrachloride and 100 g of anhydrous hydrogen fluoride were supplied through a preheating tube for 31 minutes, and a gas phase reaction was carried out at 400° C. while controlling the temperature. The exhaust gas from the reaction tube was condensed and purified to obtain 149g of oil.
This was distilled and purified to collect 46.7 g of 2-chloro-5-trifluoromethylpyridine. The recovered oil after separation contains 21% of 2-chloro-5-trifluoromethylpyridine, 15.3% of 2-chloro-3-trifluoromethylpyridine and 17% of 2.6-dichloro-3-trifluoromethylpyridine.
It was contained.

(3) Reduction of chloro-3-trifluoromethylpyridines 180 g of the recovered oily substance of the chloro-3-trifluoromethylpyridines was dissolved in 400 ml of acetic acid,
It was heated to about 90°C and 98g of zinc powder was gradually added over a period of 2 hours at 90-100°C. Then 110
The mixture was heated to ℃ and refluxed for 1 hour to react. The reaction product was purified to obtain 44 g of 3-trifluoromethylpyridine.

Claims (1)

[Claims] 1. One member selected from the group consisting of 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethylpyridine, and 2,6-dichloro-3-trifluoromethylpyridine. Or, a method for producing 3-trifluoromethylpyridine, which comprises producing 3-trifluoromethylpyridine by reducing two or more types of chloro3-trifluoromethylpyridines. 2 β-picoline is chlorinated and fluorinated simultaneously or sequentially in the presence of an inert diluent in a gas phase to produce 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethylpyridine and One or more chloro-3-trifluoromethylpyridines selected from the group consisting of 2,6-dichloro-3-trifluoromethylpyridine are produced, and this is reduced to produce 3-trifluoromethylpyridine. A method for producing 3-trifluoromethylpyridine.