JPS6144831A - Production of fluorinated benzene - Google Patents

Abstract

PURPOSE:To obtain the titled substance, in high yield, without producing by- products, facilitating the temperature control of the reaction system by the exothermic reaction, by reacting a chlorinated nitrobenzene with a fluorination agent at a high temperature in a solvent consisting of benzonitrile which is a thermally stable compound having no hygroscopicity. CONSTITUTION:A chlorinated nitrobenzene of formula I (l is 1-2; m is 1-5; n is 0-4; l+m+n is integer of <=6) is made to react with a fluorination agent such as potassium fluoride, cesium fluoride, etc. at 190-350 deg.C, preferably 230-320 deg.C under autogeneous pressure, in benzonitrile, to obtain the compound of formula II(r is 0-2; p is 0-5; q is 1-5; r+p+q is <=6). The fluorination agent is preferably a mixture of 1mol of potassium fluoride and <=0.3mol of cesium fluoride.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing fluorinated benzenes.

In particular, the general formula (I) consists of reacting chlorinated nitrobenzenes of the general formula (I) with a fluorinating agent, in particular with potassium fluoride, in a benzonitrile medium at a temperature in the range of 190 to 350°C. This invention relates to a method for producing fluorinated benzenes represented by IF).

(However, in the formula, l is an integer of 1 to 2, m is an integer of 1 to 5, and n is an integer of O to 4. Also, 1, m, and n
The sum is an integer less than or equal to 6. ) (In the formula, r is an integer of 0 to 2, p is an integer of 0 to 5, and q is an integer of 1 to 5. Also, r, p and q
The sum is an integer less than or equal to 6. ) The fluorination reaction, in which a halogen atom or a nitro group is exchanged with a fluorine atom by reacting an alkali fluoride or the like with an aromatic halide or an aromatic nitro compound, has been known for a long time. At that time, dimethyl sulfoxide (DMSO) and sulborane (1MS02) are generally used as solvents.
, N-dimethylformamide (DMF), N-methyl-
2-pyrrolidone (NMP), dimethylsulfone (DM
Aprotic polar solvents such as SO2 are mainly used, and the halogen exchange reaction is carried out at a temperature below the boiling point of the solvent.

(For example, Ishikawa, Organic Synthetic Chemistry Association, Vol. 25, No. 80.
8 pages (1967) (hereinafter referred to as Document 1), H.
HudliCky, CMlliStryof 0r(
lanicFIuorir+a Compounds,
Page 112 (1976) John Wiley &amp;
5ons Publishing, etc.). In some cases, phase transfer catalysts such as crown compounds are added to speed up the reaction rate.

However, the solvents commonly used in the above method are 1. If the reaction temperature is increased or used for a long time in order to improve the yield, decomposition reactions of the solvent or side reactions between the solvent and the raw materials or products occur, and the yield cannot be improved. 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 chlorine atoms in chlorinated nitrobenzenes are exchanged with fluorine atoms, the ortho and para positions of the nitro group, which is an electron-withdrawing group, are likely to be exchanged, as shown in the reaction example of Reference 1. Exchanging meta positions is difficult.

When producing fluorinated benzenes, the present inventors believe that the conventional methods have many drawbacks and are impossible to implement industrially, and in some cases, they have conducted intensive research into a method that allows the meta-position of the nitro group to be exchanged with halogen. As a result, b-rolated nitrobenzenes of the general formula (I>) are reacted in a benzonitrile medium at temperatures ranging from 190 to 350° C. with a fluorinating agent, in particular with potassium fluoride, at least under autogenous pressure. As a result, not only can the fluorinated benzenes represented by the general formula (II) be produced in high yield, but also the benzene fluorinated at the meta-position relative to the nitro group can be produced with superior selectivity compared to conventional methods. The present invention was completed by discovering that it is possible to produce similar products.

(However, in the formula, yaku is an integer of 1 to 2, m is an integer of 1 to 5, and n is an integer of 0 to 4. Also, 1, Peng, and n
The sum is an integer less than or equal to 6. ) (In the formula, r is an integer of 0 to 2, p is an integer of 0 to 5, and q is an integer of 1 to 5. Also, r, p and q
The sum is an integer less than or equal to 6. ) Specific production examples of fluorinated nitrobenzenes in the present invention include the following. That is, from 2-chloronitrobenzene to 2-fluoronitrobenzene,
Production, production of 4-fluoronitrobenzene from 4-chloronitrobenzene, production of 3-di-0-2-fluoronitrobenzene or 2-fluoronitrobenzene from 2゜3-dichloronitrobenzene
．． Production of 3-difluoronitrobenzene, Production of 2.4-difluoronitrobenzene from 2.4-dichloronitrobenzene, 5-difluoronitrobenzene from 2.5-dichloronitrobenzene
Chloro-2-fluoronitrobenzene or 2.5-
Production of difluoronitrobenzene, 3. Production of 3-chloro-4-fluoronitropene, zene or 3.4-difluoro[1-nitrobenzene from 4-dichloronitrobenzene, 3-chloro-4-fluoronitrobenzene from 2.3.4-trichloronitrobenzene.
Chloro-2゜4-difluoronitrobenzene or 2
, 3゜Production of 4-trifluoronitrobenzene, 2.4
Production of 2.4.6-trifluoronitrobenzene from ゜6-trichloronitrobenzene, Production of 3,5-dichloro-4-fluoronitrobenzene or 3,4゜5-trifluoronitrobenzene from 3.4.5-trichloronitrobenzene, 2.3゜5.6-tetrachloro-1
, Production of 2.3.5.6-tetrachloro-4-fluoronitrobenzene from 4-dinitrobenzene, Production of 2,3-difluoronitrobenzene from 3-chloro-2-fluoronitrobenzene, 3-chloro-2,4- Difluoronide "1 Production of 2.3.4-trifluoronitrobenzene from benzene, production of bentaf[]]rofluorobenze from pentachloronitrobenzene, 2.3.5.6
(2.3, 5.6 from -butlav 1 colonitrobenzene
-Production of chitrachlorofluorobenzene, etc.

Since the WI medium benzonitrile in the present invention is thermally stable, the temperature is considered to be necessary for fluorination reaction of chlorinated nitrobenzenes to fluorinated benzenes19
It can be used even in the ma range of 0 to 350°C, and 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 preventing the formation of a large amount of carbide, unlike a manufacturing method without a solvent. have sex.

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. many.

In some cases, transition metal fluorides such as andimony 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 α3 t )L/or less to 1 mole of potassium fluoride.

The fluorinating agent is required in an amount at least equivalent to the chloro atom and -NO2 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 is 1 to 2 moles of potassium fluoride based on the chloro atom and nido O group substituted for the fluorine atom in the chlorinated nidobenzene.

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 a low temperature, the reaction rate will be reduced and productivity will be poor, while if the temperature is high, carbides will be produced and the NO2 removal reaction will likely occur. In either case, the yield of fluorinated benzenes decreases.

In the present invention, a gauge pressure of up to about 15 Kfl/cd is shown at a temperature range of 190° C. to 350° C. in order to carry out the reaction under naturally occurring pressure, but the pressure may be further increased with an inert gas such as nitrogen.

The reaction time varies depending on the reaction temperature, but is suitably in the range of about 2 hours to 48 hours.

The raw material chlorinated nitrobenzene is preferably added to the reaction system in an amount of about 5 to 50 parts per 6100 parts by weight of the solution.

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 DMSO1TMSO2, DMF, NM
Aprotic polar solvents such as P and 0MS02 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 in advance by distillation 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 speeds up the reaction rate and can shorten the reaction time.

As a phase transfer catalyst, dibenzo-18-crown-6
- Crown compounds such as ethers, molecular weight 300-600
Polyethylene glycol and the like can be used.

The amount added is 0 for chlorinated nitrobenzenes.
．． 0.01 mol to 0.25 mol is suitable.

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 products and intermediates in which chlorine is not substituted with Fluorine are
Unreacted substances and intermediates can also be easily converted into the desired product by recovering them by distillation or the like and reusing them together with benzonitrile, which is a solvent, in the next reaction.

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 cx of benzonitrile, 40 q (0,208 mol) of 2,3-dichloronitrobenzene, and 19.3a (0,332 mol) of dry potassium fluoride in the form of fine particles were charged into a 200 cc stainless steel autoclave, and the inside of the reaction vessel was charged. After replacing the air with nitrogen gas, the temperature was increased to 290℃ (5,0K
9/tri G) for 30 hours to react. After the reaction was completed, the reaction solution was separated from potassium chloride and unreacted potassium fluoride using a rotary evaporator under final conditions of an external temperature of 160° C. and a degree of vacuum of 20 Torr. When the separated liquid was analyzed using a gas chromatograph using column packing material: 5E52 (1 ml) and a ram tank wetness of 60°C, it was found that 82.5 mol% of 3-chloro-2-fluoronitrobenzene was added to the charged 2°3-dichloronitrobenzene. It was done. The separated liquid is purified using a precision fractionator to obtain the desired product 3.
-chloro-2-fluoronitrobenzene 28.30 (8
110-112° C. fraction) could 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 10 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.

Claims (4)

[Claims] (1) A general method characterized by reacting a chlorinated nitrobenzene represented by the general formula (I) 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 a fluorinated benzene represented by formula (II). ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) (However, in the formula, l is an integer of 1 to 2, m is an integer of 1 to 5, and n is an integer of 0 to 4. The sum of , m, and n is an integer of 6 or less.) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) (However, in the formula, r is an integer from 0 to 2, and p is an integer from 0 to 5. , and q is an integer from 1 to 5. Also, the sum of r, p, and q is an integer of 6 or less.) (2) the fluorinating agent is at least one selected from the group consisting of alkali metal and alkaline earth metal fluoride salts;
The method according to claim (1), which is a species. (3) The method according to claim (1) or (2), wherein the fluorinating agent is potassium fluoride. (4) The method according to claim (1) or (2), wherein the fluorinating agent is a mixture of potassium fluoride and cesium fluoride.