JPS6094919A - Production of organic fluoride - Google Patents

Abstract

PURPOSE:To produce an organic fluoride easily, in high yield, by carrying out the halogen-exchange reaction of a chlorinated or brominated orgaic compound with a fluorination agent using benzonitrile as a solvent at a temperature above the boiling point of the solvent. CONSTITUTION:A chlorinated or brominated organic compound (e.g. chlorobenzene, pantachlorobenzonitrile, etc.) is made to react with a fluorination agent (especially preferably potassium fluoride) in benzonitrile solvent at a temperature above the boiling point of benzonitrile, i.e. at 190-400 deg.C, preferably 230-360 deg.C under autogeneous pressure, preferably in the presence of a phase transfer catalyst to obtain an organic fluorine compound (e.g. 3,5-dichloro-2,4,6-trifluorobenzonitrile). The benzonitrile used as the solvent can be separated easily from the reaction product and reused.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the reaction of chloro- or brominated organic compounds with fluorinating agents, in particular potassium fluoride, in a benzonitrile medium in the temperature range from 190°C to 400°C, by means of the so-called halogen exchange reaction. This article relates to a method for producing fluorine compounds.

Exchanging the halogen atom with a fluorine atom by reacting an alkali fluoride on an aromatic halide (DMSO),
Sulfolane (TMSO2), N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP),
So-called aprotic polar solvents such as dimethyl sulfone (DIVIS 02) are mainly used.
ry of Organic Fluorine Co
mpounds 112 pages, 1976 Whi l
ey Publishing, etc.].

When these commonly used solvents are used for a long time at high temperatures to improve yields, decomposition reactions of the solvents or side reactions between the solvents and raw materials or products may occur, resulting in lower yields. I can't improve.

It also has the disadvantage that it is not easy to use industrially in terms of solvent recovery and reuse. These melts are
In order to avoid the drawback that the reaction cannot be used at high temperatures, it is also common to carry out the reaction at a high temperature of 200 to 500° C. without using a solvent and using an autoclave. However, since it does not use an external continuous system, 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 a difficult method to implement industrially.

The present inventors have intensively studied a method that can be industrially implemented to improve the above-mentioned drawbacks, and the present inventors have developed a method using a benzonitrile-containing solvent and reacting it with a warming agent having a temperature higher than the boiling point of benzonitrile, especially potassium fluoride. The present inventors have discovered that organic fluorine compounds can be easily produced in good yield by halogen exchange, and have completed the present invention.

The invention will be explained in more detail below.

The solvent benzonitrile used in the present invention is thermally stable even at high temperatures during the halogen exchange reaction, and there is no side reaction between the solvent and the raw material or product as seen in other solvents, so it can be used at temperatures of 190 to 400°C. Can be used in a high temperature range of
Therefore, the reaction rate can be increased and the yield can also be improved. In addition, the use of this solvent has the advantage that temperature control is easy and the formation of a large amount of carbide can be prevented, unlike the production method without a melt, and it is possible to obtain the target product in high yield during industrial implementation. can.

The solvent benzonitrile used in the present invention differs from commonly used aprotic polar solvents in that it has a very low ability to dissolve inorganic salts below its boiling point. In the commonly performed nitrogen exchange reaction, it is necessary to use a solvent that has the ability to dissolve the fluoride salt, which is the fluorinating agent.

For this purpose, aprotic polar solvents that generally have a high ability to dissolve inorganic salts such as DMSO1T M S 02, DMF, and NMP are used.
, DMSO2, etc., and it was considered disadvantageous to use benzonitrile, which has a low ability to dissolve inorganic salts, as in the present invention. Facts G, C, Ftnger et al., J, Am
er, Chem, Soc, + Vol. 78, p. 6034 (1956), using benzonitrile as a solvent, potassium fluoride was used as a fluorinating agent (!: L, 2.4-dinitrochlorobenzene 2.4 - There are 6 examples of halogen exchange cities in cy=MO fluorobenzene, but the reaction temperature is 15
Since the temperature is as low as 0 to 170°C, the yield is low. Also, G, Ful
ler, J., Chem., Soc.

As described in 1965, p. 6264, we are investigating the solubility of hesakichlorobenzene in halogen exchange using potassium fluoride as a fluorinating agent, but unlike other solvents, benzene) There are also known cases where no logen exchange occurred even after using it as a solvent and reacting at 175°C for 18 hours.

According to research conducted by the present inventors, when benzonitrile is used at a temperature above its boiling point, the solubility of fluorinating agents such as potassium fluoride increases rapidly. The ability to increase the solubility of the fluorinating agent can be said to be a factor in dramatically increasing the yield of organic fluorine compounds in the present invention.

In general, /-logen exchange of polynologenides is difficult. R, E., BanKs et al., Chem &, Ind.
As described in Vol. 1964, p. 835, Ishikawa, Nikkashi, Vol. 86, p. 90, the halogen exchange rate is low, but in the present invention, it is easy to increase the halogen exchange rate, and generally aromatic Electron-withdrawing -CN group in the compound, NO
It is said that meta-position norogens such as 2 groups are difficult to be substituted, but any compound containing at least one chlorine atom or bromine atom can be used for the meta-position norogens as well. .

Specifically, chlorobenzene, polychloropenzey, O
-chlornitrobenzene, P-chlornitrobenzene,
2.4-dinitrochlorobenzene, 0-chlorobenzonitrile, m-chlorobenzene) IJ/l/, P-chlorobenzonitrile, 2,6-cyclohenzonitrile, 3
, 5-cyclopenzonitrile, pentachlorobenzonitrile, 3-chlorophthalic anhydride, 3,6-dichlorophthalic anhydride, tetrachlorophthalic anhydride, tetrachlorophthalonitrile, tetrachloroisophthalonitrile, tetrachloroterephthalo Nitrile, chloranyl, 2-chloropyridine, 2.5-dichloropyridine, pentachlorpyridine, tetrachlorpyrimidine, chlornaphthalene, polychlornaphthalene, dichloromaleic anhydride, etc.
Alternatively, compounds having a bromine atom instead of chlorine in these compounds are exemplified.

As the fluorinating agent used in the halogen exchange reaction, alkali fluorides such as cesium fluoride, potassium fluoride, and sodium fluoride, and alkaline earth metal fluoride salts such as calcium fluoride are generally used. In some cases, a transition metal fluoride such as antimony fluoride may also be 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.

The fluorinating agent must be used in an amount of at least more than the light amount for the chlorine atom to be substituted by the fluorine atom in the raw material chlor or bromine compound, and in the case of potassium fluoride, the amount of fluorinating agent is 1 to 2 per chromium or bromine atom. A molar range is suitable.

In the present invention, it is preferable to carry out the reaction under naturally occurring pressure, but the reaction may also be carried out at a higher pressure, particularly using an inert gas such as nitrogen.

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

The organic compound used as the raw material is Soge 100! It is preferably added to the reaction system in an amount of about 5 parts to 50 parts based on the volume.

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□, DMF, NM
P.

Aprotic polar solvents such as DMSO2 are highly hygroscopic and contain considerable water content. Therefore, prior to the reaction, it is necessary to add benzene, toluene, etc. to remove water by distillation as an azeotrope. In the case of "unexploded gas", benzonitrile is highly hygroscopic, so this operation is not necessary in principle. However, potassium fluoride used as a fluorinating agent is highly hygroscopic, so in some cases it may be better to add benzene, toluene, etc. to remove water by distillation in advance as an azeotrope.

In the present invention, it is advantageous to further include a phase θ transfer agent in the reaction system. That is, the presence of the phase a transfer catalyst has the advantage of increasing the reaction rate and shortening the reaction time.

n 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 of this phase transfer catalyst added is 0-01 mol to 0.01 mol to 1 mol of the raw material chloro or bromine organic compound.
25 moles is suitable.

The organic fluorinated compounds obtained by the present invention include fluorobenzene, polyfluorobenzene, 0-fluoronitrobenzene, P-fluoronitrobenzene, 2,4-dinitrofluorobenzene, O-fluorobenzonitrile, m-fluorobenzonitrile, and P-fluorobenzonitrile. Benzonitrile, 2,6-difluorobenzonitrile, 3,5-
Difluorobenzonitrile, 3,5-Zinluor 2.
4.6-) Dichlorobenzonitrile, 3-fluorophthalic anhydride, 3.6-difluorophthalic anhydride, tetrafluorophthalonitrile, 5-chloro-trifluoroinphthalonitrile, tetrachloroterephthalonitrile, 2
, 5-cyclo-3,6-cyfluorobarabenzoquinone, 2-fluoropyridine, 2,5-difluoropyridine, 3,5-dichloro-2,4,6-)lifluoropyridine, 5-chloro-trifluoropyridine Q gin, fluoronaphthalene, difluoromaleic anhydride, etc., agricultural chemicals, pharmaceuticals,
Examples include compounds useful as synthetic intermediates such as dyes.

The main solvent, benzonitrile, can be easily separated from the product by distillation and can be reused as 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 1 200 r of benzonitrile and g of pentachlorobenzonitrile in a 500Cl stainless steel container autoclave
o, o y (0,291 mol) and 65.9 y (1,135 mol) of finely dried potassium fluoride were charged, and after replacing the air in the reaction vessel with nitrogen gas, 270
The mixture was heated and stirred at ℃ for 4 hours. After the reaction is completed, use a rotary evaporator to reduce the external temperature to 180°C and the vacuum level to 20 Torr.
The reaction solution was separated from potassium chloride and unreacted potassium fluoride with a final surface property of r. The separated reaction solution was purified using a precision fractionator to obtain the desired product 3°s-cyclo2.4.
6-) Lifluorobenzonitrile (normal pressure 222-224
°C fraction) s 6.82 (yield 86.3 relative to charged pentachlorobenzonitrile, purity 98.2%) was recovered.

Example 2 Add 200% benzonitrile to an autoclave in a 5000C stainless steel container. , tetrachloroorthophthalonitrile s o, o y (o, s 0 1 mol), fine particulate dry potassium fluoride s 3.9 y (1,444 mol) were all charged, and the air in the reaction vessel was purged with nitrogen gas. After replacing the mixture, the mixture was heated and stirred at 230°C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, and suspended potassium chloride and unreacted potassium fluoride were removed by filtration. Filler: SE521m with benzonitrile solution of mother liquor.

When analyzed by gas chromatography at a column bath temperature of 60° C., 87.7 mol of tetrafluoroorthophthalonitrile was replaced with respect to the unloaded tetrachloroorthophthalonitrile.

By removing the benzonitrile by vacuum distillation, crystals of tetrafluoroorthophthalonitrile (M, P 86-87°C) solidified at room temperature were recovered.

Example 3 In a 500° stainless steel container autoclave, add 200ml of benzonitrile and 80ml of 3,5-dichloro-2,4°6-drifluorobenzonitrile. Of (0,354 mol), finely particulate dry potassium fluoride 45.2 f(o,,
After replacing the air in the reaction vessel with nitrogen gas, the mixture was heated and stirred at 330°C for 12 hours. After the reaction is complete, use a low evaporator to reduce the temperature to 150 to 180
The reaction solution was separated from potassium chloride and unreacted potassium fluoride under reduced pressure at °C. When the separated liquid was analyzed using a gas chromatograph using a column packing material: Salmon 1oo02nis and a column tank temperature of 60°C, it was found that pentafluorobenzonitrile was 96.8% compared to the charged 3,5-dichloro-2,4,6-dolifluorobenzonitrile. I was transferred to the mall.

Using the separated liquid using a precision fractionator, 62.89 g of the desired product, pentafluorobenzonitrile, was recovered. When this fraction was analyzed by gas chromatography, almost no peaks of components other than pentafluorobenzonitrile were observed.

Example 4 Benzonitrile 407 and Orun Chlortoluene 78V (0,063
2 mol), finely particulate dry potassium fluoride 7.33 t
(0,1265 mol) was charged, the air in the reaction vessel was replaced with nitrogen gas, and the mixture was heated and stirred at 370°C for 24 hours. The reaction solution was separated from potassium chloride and unreacted potassium fluoride under reduced pressure using a rotary evaporator. The separated benzonitrile solution was used as a filler: Sumon 100
02m: Column tank temperature 60' When analyzed by CO gas chromatography, 22 mol of orthofluorotoluene was added to the charged orthochlorotoluene.

Example 5 Benzonitrile 40F, 2,4-dinitrochlorobenzene 1 in a 100Ω stainless steel container autoclave 6.
o y (0,079 mol) and 5.59 (0,095 mol) of finely divided dry potassium fluoride were charged, and after replacing the air in the reaction vessel with nitrogen gas, the mixture was heated and stirred at 235° C. for 3 hours. After the reaction was completed, the mixture was cooled to room temperature and suspended potassium chloride and unreacted potassium fluoride were removed by filtration. Filler: SE52 with benzonitrile solution of mother liquor
When analyzed using a gas chromatograph at a 1ms column bath temperature of 120°C, 2,4-dinitrofluorobenzene was 94% compared to the 2,4-dinitrochlorobenzene used.
0 mol% was depleted.

Example 6 Benzonitrile 40t1 Hexachlorobenzene8. Oy (0,
02 smol), fine particulate dry potassium fluoride 14.6
q (0.2s, 2 moles), the air in the reaction vessel was replaced with nitrogen gas, and then heated and stirred at 350°C for 30 hours. After the reaction was completed, the mixture was cooled to room temperature, and turbid potassium chloride and unreacted potassium fluoride were removed by filtration.

Mother liquor benzonitrile solution as filler; Salmon 1000
2n+, Casino, tank temperature 60-120°C (rising temperature) gas chromatograph analysis revealed that hexafluorobenzene was 20.3 mol% and monochlorobenzofluorobenzene was 57.1 mol% dichlorobenzene based on the hexachlorobenzene used. 10.6 mol% of tetrafluorobenzene was converted.

Patent applicant: Nippon Shokubai Kagaku Kogyo Co., Ltd. Procedural amendment (spontaneous) Date of Z/2F, 1980 Manabu Shiga, Commissioner of the Patent Office 1, Indication of the case, Patent Application No. 202590 of 1982, 2, Title of the invention: Organic Fluoride manufacturing method 3, person making the amendment 1゛1 product'1 Applicant: 5-1 Koraibashi, Higashi-ku, Osaka-shi, Osaka (462) Nippon Shokubai Chemical Co., Ltd. Representative Director Mitsu Ishikawa 4, Agent: -100 Nippon Shokubai Chemical Co., Ltd., Tokyo Branch, 1-2-2 Nazai-cho, Chiyoda-ku, Tokyo 5, Detailed explanation of the invention in the application specification to be amended, Section 6, Contents of the amendment (1) Description Add the following statement on the next line of page 15, line 18.

[Example 7 40 g of benzonitrile 1 1 pentabromobenzonitrile was placed in an autoclave in a 100 cc stainless steel container.
6 g ((1,0322 mol) JjJ, and 103 g (0,177 mol) of finely dried potassium fluoride were charged, and the air in the reaction vessel was replaced with nitrogen gas.
The mixture was heated and stirred at 0° C. for 5 minutes. After the reaction, Example 1
When the mother liquor obtained in the same manner was analyzed by gas chromatography, 71.9% of pentafluorobenzonitrile was obtained based on the charged pentabromobenzonitrile, which was 7.1%.

Example 8 40 g of benzonitrile, 12.0 q (0,0811 t) of 2,5-dichlorpyridine, and 12.3 g (0,0811 t) of finely dried potassium fluoride were added to the t-1 clay cap of a 100 cc stainless steel container. , 212 mol) and replaced the air in the reaction vessel with nitrogen gas, and then heated at 370°C for 2
Heat and stir for 4 hours (). The reaction solution was separated from potassium chloride and unreacted potassium fluoride under reduced pressure using a 11-tally evaporator. The separated benzonitrile solution was packed into a column using Leamon 1000.2m, column 1?
W'Ia 71 (i0℃ analysis by graph) 2,5-difluoropyridine 66.6 mol% based on the charged 2,5-dichloropyridine
and 25.4 mol % of 5-chloro-2-fluoro[1-pyridine were obtained. Each peak is a gas chromatograph.
As a result of analysis using a mass spectrometer (GC-MS), the resulting quality n1 spectra confirmed that they were 2.5-rodifluoropyridine and 5-rl@-2-fluoropyridine, respectively.

”

Claims (1)

[Claims] (1) A process for producing an organic fluorine compound, characterized by reacting a chloro or brominated organic compound with a fluorinating agent under spontaneous pressure in a benzonitrile medium at a temperature in the range of 190 to 400°C. . 421 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. (31) The method according to claim 1+, wherein the fluorinating agent is potassium fluoride. Method.