JPH0119369B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing fluorinated benzenes. Specifically, the chlorinated nitrobenzenes represented by the general formula () are treated in a benzonitrile medium at 190
The present invention relates to a process for producing fluorinated benzenes of the general formula (), which comprises reacting with a fluorinating agent, in particular potassium fluoride, at a temperature in the range from ~350°C. (However, in the formula, l is an integer of 1 to 2, m is 1 to
is an integer of 5, and n is an integer of 0 to 4.
Further, the sum of l, m, and n is an integer of 6 or less. ) (However, in the formula, r is an integer of 0 to 2, p is 0 to
is an integer of 5, and q is an integer of 1 to 5.
Further, the sum of r, p, and q is an integer of 6 or less. ) The fluorination reaction, in which an aromatic halide or an aromatic nitro compound is reacted with an alkali fluoride or the like to exchange a halogen atom or a nitro group with a fluorine atom, has been known for a long time. In this case, commonly used solvents include dimethyl sulfoxide (DMSO), sulfolane (TMSO ₂ ), N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), and dimethyl sulfone (DMSO ₂ ).
Aprotic polar solvents are mainly used, and the halogen exchange reaction is carried out at a temperature below the boiling point of the solvent. [For example, Ishikawa, Journal of the Society of Organic Synthetic Chemistry, Vol. 25,
No. 808 (1967) (hereinafter referred to as Document 1), M.
Hudlicky, Chemistry of Organic Fluorine
Compounds, p. 112 (1976) John Wiley &
Sons Publishing, etc.]. In some cases, a phase transfer catalyst such as a crown compound is added to speed up the reaction rate. However, if the solvents commonly used in the above methods are used at high reaction temperatures or for long periods of time to improve yields, they may cause decomposition reactions or side reactions between the solvent and raw materials or products. occurs, and the yield cannot be improved after all. It also has the disadvantage that it is not easy to use industrially in terms of solvent recovery and reuse. In order to avoid the drawback that these solvents cannot be used at high temperatures, it is also common to carry out the reaction without a solvent at high temperatures of 190 to 500°C using an autoclave. However, since no solvent is used, it is difficult to control the temperature due to the exothermic reaction, and a large amount of carbide adheres to the container after the reaction is completed, making it difficult to implement industrially. Furthermore, in the above method, when replacing the chlorine atom in the chlorinated nitrobenzene with a fluorine atom,
As shown in the reaction of Document 1, the ortho and para positions of the nitro group, which is an electron-withdrawing group, are easily exchanged, but it is difficult to exchange the meta position. When producing fluorinated benzenes, the present inventors believe that general methods have many drawbacks and are impossible to implement on an industrial scale, and in some cases, we are working diligently to develop a method that allows halogen exchange at the meta position of the nitro group. Studies have shown that chlorinated nitrobenzenes of the general formula () react with fluorinating agents, especially potassium fluoride, in benzonitrile medium at temperatures ranging from 190 to 350°C under at least spontaneous pressure. By this method, not only can the fluorinated benzenes represented by the general formula () be produced in high yield, but also the meta-position relative to the nitro group can be fluorinated with superior selectivity compared to conventional methods. The present invention was completed by discovering that it is possible to produce benzenes. (However, in the formula, l is an integer of 1 to 2, m is 1 to
is an integer of 5, and 2 is an integer of 0 to 4.
Further, the sum of l, m, and n is an integer of 6 or less. ) (However, in the formula, r is an integer of 0 to 2, p is 0 to
is an integer of 5, and q is an integer of 1 to 5.
Further, the sum of r, p, and q is an integer of 6 or less. ) Specific examples of production of fluorinated benzenes in the present invention include the following. That is, 2
-Production of 2-fluoronitrobenzene or 1,2-difluorobenzene from chloronitrobenzene, production of 4-fluoronitrobenzene from 4-chloronitrobenzene, 3-chloro-2-fluoronitrobenzene, 2,3- from 2,3-dichloronitrobenzene Production of difluoronitrobenzene or 2,3-difluorochlorobenzene, 2,4-difluoronitrobenzene from 2,4-dichloronitrobenzene
-Production of difluoronitrobenzene, production of 5-chloro-2-fluoronitrobenzene from 2,5-dichloronitrobenzene, production of 2,5-difluoronitrobenzene or 3,4-difluorochlorobenzene, production of 3-chloro-4 from 3,4-dichloronitrobenzene -Fluoronitrobenzene,
3,4-difluoronitrobenzene or 2,
Production of 5-difluorochlorobenzene 2,3,4
-3-chloro from trichloronitrobenzene-
2,4-difluoronitrobenzene, 2,3,4
-trifluoronitrobenzene or 2,3,
Production of 6-trifluorochlorobenzene, 2,
4,6-trichloronitrobenzene to 2,4,
Production of 6-trifluoronitrobenzene, 3,
4,5-trichloronitrobenzene to 3,5-
Production of dichloro-4-fluoronitrobenzene or 3,4,5-trifluoronitrobenzene, 2,3,5,6-tetrachloro-4- from 2,3,5,6-tetrachloro-1,4-dinitrobenzene Production of fluoronitrobenzene, from 3-chloro-2-fluoronitrobenzene to 2,3-
Production of difluoronitrobenzene or 2,3-difluorochlorobenzene, production of 3,4-difluoronitrobenzene or 2,5-difluorochlorobenzene from 3-chloro-4fluoronitrobenzene, production of 2,3-difluoronitrobenzene from 3-chloro-2,4-difluoronitrobenzene , Production of 4-trifluoronitrobenzene or 2,3,6-trifluorochlorobenzene, Production of pentachlorofluorobenzene from pentachloronitrobenzene, 2,3,5,6- from 2,3,5,6-tetrachloronitrobenzene Production of tetrachlorofluorobenzene, from 2,3,4,5-tetrachloronitrobenzene to 3,5-dichloro-2,4-difluoronitrobenzene, 2,3,4,5-tetrafluoronitrobenzene or 1,3-dichloro- These include the production of 2,4,5-trifluorobenzene. The solvent benzonitrile used in the present invention is thermally stable, so it can be used in the temperature range of 190 to 350°C, which is considered the temperature required to fluorinate chlorinated nitrobenzenes to fluorinated benzenes. It also has the advantage that there is no side reaction between the solvent and raw materials or products, which occurs with other solvents. In addition, the use of this solvent has the advantage of being able to easily control the temperature and prevent the formation of a large amount of carbide, unlike a manufacturing method without a solvent, making it possible to obtain the desired product in high yield during industrial implementation. have an advantage. The fluorinating agent used in the halogen exchange reaction is generally an alkali fluoride such as cesium fluoride, potassium fluoride, or sodium fluoride, or an alkaline earth metal fluoride salt such as barium fluoride or calcium fluoride. There are many. In some cases, transition metal fluorides such as antimony fluoride are also used. In the present invention, any commonly used fluorinating agent can be used. Among these, particularly preferred is potassium fluoride, which is easy to handle and commercially available. It is also particularly preferable to add cesium fluoride at a ratio of 0.3 mole or less to 1 mole of potassium fluoride. The fluorinating agent is required in an amount at least equivalent to the chloro atom and --NO ₂ group to be substituted by the fluorine atom in the chlorinated nitrobenzene as the raw material.
When the fluorinating agent is potassium fluoride, the appropriate amount of potassium fluoride is 1 to 2 moles per chloro atom and nitro group substituted for the fluorine atom in the chlorinated nitrobenzene. The reaction temperature of the present invention is preferably in the range of 190 to 350°C. Particularly preferred is 230 to 320°C. If the reaction is carried out at low temperature, the reaction rate will decrease and productivity will deteriorate.
At high temperatures, carbides are formed and NO ₂ removal reactions are more likely to occur. In either case, the yield of fluorinated benzenes decreases. In the present invention, in order to react under naturally occurring pressure,
It exhibits a gauge pressure of up to about 15 kg/cm ² in a temperature range of 190°C to 350°C, but may be further pressurized with an inert gas such as nitrogen. The reaction time varies depending on the reaction temperature, but is approximately 2
A range of 48 hours is appropriate. The raw material chlorinated nitrobenzene is
It is preferably added to the reaction system in a range of about 5 parts to 50 parts by weight. It is generally said that it is preferable to carry out the halogen exchange reaction under anhydrous conditions as much as possible in order to increase the reaction rate and avoid side reactions. Commonly used DMSO, TMSO ₂ , DMF,
Aprotic polar solvents such as NMP and DMSO ₂ are highly hygroscopic and contain a considerable amount of water.
Therefore, prior to the reaction, it is necessary to add benzene, toluene, etc. to remove water by distillation as an azeotrope. In the present invention, benzonitrile does not have hygroscopic properties, so its operation is not required in principle. However, potassium fluoride used as a fluorinating agent has high hygroscopicity, so in some cases it is preferable to add benzene, toluene, etc. to remove water by distillation in advance as an azeotrope. In the present invention, a phase transfer catalyst may be present in the reaction system. That is, the presence of a phase transfer catalyst has the advantage of increasing the reaction rate and shortening the reaction time. As phase transfer catalysts, crown compounds such as dibenzo 18-crown-6-ether, molecular weight
300 to 600 polyethylene glycol, etc. can be used. The appropriate amount to be added is 0.01 mol to 0.25 mol relative to the chlorinated nitrobenzenes. Benzonitrile, the solvent used in the present invention, can be easily separated from the product by distillation and can be reused as a solvent in the next reaction. In addition, unreacted substances and intermediate substances in which chlorine has not been replaced with fluorine can be recovered by distillation, etc., and reused together with benzonitrile, which is a solvent, in the next reaction. Can be easily converted into objects. EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited thereto. Example 1 100 g of benzonitrile, 40 g (0.208 mol) of 2,3-dichloronitrobenzene, and 19.3 g (0.332 mol) of finely dried potassium fluoride were charged into a 200 c.c. stainless steel autoclave, and the air inside the reaction vessel was charged. After replacing with nitrogen gas, the temperature was 290℃ (5.0
Kg/cm ² G) was heated and stirred for 30 hours to react. After the reaction is complete, use a rotary evaporator to reduce the temperature to outside temperature.
The reaction solution was separated from potassium chloride and unreacted potassium fluoride under the final conditions of 160° C. and 20 Torr of vacuum. When the separated liquid was analyzed using a gas chromatograph using a column packing material of SE52 (1 m) and a column bath temperature of 60°C, it was found that 3-chloro-2-fluoronitrobenzene was detected compared to the charged 2,3-dichloronitrobenzene.
82.5 mol% was obtained. The separated liquid was purified using a precision fractionator, and the target product 3-chloro-2-fluoronitrobenzene 28.3g (8mmHg 110-112℃ fraction) was obtained.
was able to be recovered. When this fraction was analyzed by gas chromatography, almost no peaks of compounds other than 3-chloro-2-fluoronitrobenzene were observed. Examples 2 to 15 Using the same container as in Example 1, the materials were charged as shown in Table 1, and the reaction was carried out with the results shown in Table 1.

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Claims (1)

[Claims] 1. A chlorinated nitrobenzene represented by the general formula () is reacted with a fluorinating agent in a benzonitrile medium at a temperature in the range of 190 to 350°C under at least a spontaneous pressure. A method for producing fluorinated benzenes represented by the general formula (). (However, in the formula, l is an integer of 1 to 2, m is 1 to
is an integer of 5, and n is an integer of 0 to 4.
Further, the sum of l, m, and n is an integer of 6 or less. ) (However, in the formula, r is an integer of 0 to 2, p is 0 to
is an integer of 5, and q is an integer of 1 to 5.
Further, the sum of r, p, and q is an integer of 6 or less. 2. The method according to claim 1, wherein the fluorinating agent is at least one selected from the group consisting of fluoride salts of alkali metals and alkaline earth metals. 3. The method according to claim 1 or 2, wherein the fluorinating agent is potassium fluoride. 4 Claim 1 or 2, wherein the fluorinating agent is a mixture of potassium fluoride and cesium fluoride
Method described.