JPH0780791B2 - Method for producing organic fluorine compound - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing an organic fluorine compound. More specifically, it relates to a method for producing an organic fluorine compound by a so-called halogen exchange method, in which a chlorine group and / or a bromine group in an organic compound having an active chlorine group and / or a bromine group are substituted with a fluoro group.

Organic fluorine compounds are widely used as raw materials for agricultural chemicals and pharmaceuticals.

(Problems to be Solved by Conventional Techniques and Inventions) A conventional method for producing an organic fluorine compound is a so-called halogen in which an organic compound having an active chloro group or a bromine group is reacted with a fluorinating agent in an organic solvent. The exchange method is widely used because it is easy to operate.

Therefore, in the above halogen exchange method, as the fluorinating agent, alkali fluoride, especially potassium fluoride (KF) is used exclusively because it is necessary to increase the reaction yield. However, alkali fluoride, especially potassium fluoride, has a very strong deliquescent property, and therefore normally absorbs moisture in the air. Therefore, when such potassium fluoride is used as the fluorinating agent, the yield becomes extremely low, and there is a problem that it is necessary to pulverize and roast before use in order to prevent this. Also,
The above reaction often has a low reaction yield as compared with other general organic reactions.

As a means for improving the above-mentioned problems, a method using potassium fluoride (KF) synthesized by a spray drying method (Japanese Patent Laid-Open No. S60-12065)
58-65226) is also known, but even if this method is used, a high reaction yield cannot always be obtained depending on the target organic compound.

Further, in order to improve the reaction yield (reaction activity), various measures have been taken to select an organic solvent (JP-A-47-34).
236, JP-A-49-14430, JP-A-51-39633, JP-A-61-7217). However, according to the study of the present inventor, none of these methods is sufficient in terms of improving the reaction yield, and the organic solvent is dimethyl sulfoxide, dimethyl sulfone, dimethylformamide, dimethylacetamide, tetramethylene sulfone, or the like. It is necessary to use an expensive aprotic polar solvent, and therefore has the drawback of increasing the manufacturing cost.

An object of the present invention is to provide a method for producing an organic fluorine compound, which is easy to operate, has a high yield, and is inexpensive.

(Means and Actions for Solving Problems) In view of the above problems, the present inventor diligently studied a method for producing an organic fluorine compound which is easy to operate, high in yield, and inexpensive, and as a result, its activity is weak. Therefore, especially in combination with zinc fluoride (ZnF ₂ ) which was considered to be inconvenient as a fluorinating agent for halogen exchange reaction of organic compounds, in combination with an aprotic nonpolar solvent, good results were obtained. The present invention has been completed and the present invention has been completed.

That is, the present invention is a method for producing an organic fluorine compound, which comprises reacting an organic compound having an active chloro group and / or a bromine group with zinc fluoride in an aprotic apolar organic solvent.

The present invention will be described in detail.

As an organic compound used as a raw material of an organic fluorine compound (hereinafter abbreviated as a raw material organic compound), which is an object of the present invention, as long as it has an active chloro group and / or bromine group, its carbon skeleton is aromatic. Any of aliphatic compounds may be used, and compounds containing a hetero atom such as nitrogen or oxygen may be contained in the molecule. The number of active chloro groups and / or bromine groups in the above-mentioned raw material organic compound may be one or two or more in the molecule, and may be a group having both chloro groups and bromine groups.

Zinc fluoride used as a fluorinating agent in the present invention is not particularly limited in its production history, but in order to suppress side reactions during the halogen exchange reaction and improve the reaction yield, Those with as few as possible are desirable. Therefore, for example, dried zinc fluoride anhydride obtained by the reaction of zinc oxide and hydrofluoric acid, or dehydrated normal commercially available zinc fluoride tetrahydrate to give an anhydride, It is preferably used. The thus-obtained anhydrous zinc fluoride, unlike potassium fluoride and the like, exhibits almost no hygroscopicity, so that it is convenient because it requires no special measures for storage and is easy to handle. The zinc fluoride obtained as described above is further preferably heat-treated at 200 ° C. for about 4 hours, for example, in order to completely remove a small amount of water adhering to the surface prior to the halogen exchange reaction.

Further, in the present invention, it is preferable that the zinc fluoride has a high specific surface area in order to obtain a high reaction yield.
For example, it can be obtained by a method involving the reaction of zinc oxide and high-concentration hydrofluoric acid.

In the present invention, it is preferable that the raw material organic compound and the aprotic non-polar organic solvent also have a water content as small as possible. Such a raw material organic compound or organic solvent having a minimum water content can be easily obtained by distillation or treatment with a dehydrating agent such as silica gel.

In the present invention, a halogen exchange reaction is first carried out.This halogen exchange reaction is carried out by a method of suspending zinc fluoride in a mixed liquid of a raw material organic compound and an organic solvent by a means such as stirring, or a method of fluorinating the organic solvent in It is carried out by a method of suspending zinc and then adding a raw material organic compound thereto.

The reaction product thus obtained is then filtered to remove zinc chloride and / or zinc bromide produced by the above reaction and unreacted zinc fluoride, and then a mixed solution of an organic solvent and the produced organic fluorine compound is distilled or the like. By separating the both by the operation of, an organic fluorine compound as a product can be obtained. The organic solvent separated by this distillation or the like can of course be reused repeatedly.

In the present invention, the amount of zinc fluoride with respect to the raw material organic compound is equal to or more than the equivalent required for the halogen exchange reaction, and particularly 2
~ 10 times equivalents are preferred. If the amount of zinc fluoride is less than the corresponding amount, the reaction yield will be deteriorated, which is not preferable. On the contrary, if the amount is too large, not only zinc fluoride will be lost, but also
This is also not preferable because it leads to an increase in the amount of organic solvent used.

The organic solvent used in the present invention must be an aprotic non-polar solvent as described above. Specific examples of such a solvent, benzene, toluene, xylene, ethylbenzene, naphthalene, aromatic hydrocarbons such as methylnaphthalene, hexane, heptane, octane, nonane, decane, undecane, dodecane, aliphatic hydrocarbons such as tridecane, Alicyclic hydrocarbons such as cyclohexane, cycloheptane and cyclooctane, aromatic nitro compounds such as nitrobenzene, anisole, phenetole, methoxynaphthalene, diphenyl ether, dibutyl ether, dipentyl ether, dihexyl ether, tetrahydrofuran, ethers such as dioxane, chloride Alkyl chlorides such as n-propyl, isopropyl chloride, n-butyl chloride, isobutyl chloride, s-butyl chloride, t-butyl chloride, n-pentyl chloride and n-hexyl chloride, chlorobenzene And the like aromatic chlorides.

The method for producing an organic fluorine compound of the present invention is a method in which a raw material organic compound is subjected to a halogen exchange reaction using zinc fluoride as a fluorinating agent in an aprotic nonpolar solvent. It is not clear why the organic fluorine compound is obtained in a high yield by using a polar non-polar solvent, but it is probably because of the following reasons. That is, the halogen exchange reaction (fluorination reaction) with zinc fluoride is a solid-liquid reaction, but the above solvent promptly removes zinc chloride and zinc bromide produced by the reaction from the surface of zinc fluoride and exists as a solid. It is considered that the surface of zinc fluoride that is being activated is always kept in an active state.

The slurry concentration of zinc fluoride suspended in an organic solvent is
It is preferably about 5% by weight (hereinafter simply referred to as%) or more and about 50% or less. If the slurry concentration is too high, stirring becomes difficult and side reactions easily occur, and the reaction yield also decreases. On the other hand, if the slurry concentration is too low, the amount of the organic solvent used increases correspondingly, which is not preferable.

The reaction temperature and reaction time in the halogen exchange reaction are determined by the kinds of the raw material organic compound and the organic solvent. The lower the reaction temperature, and the shorter the reaction time,
It is preferable from the viewpoint of suppressing side reaction products, but the opposite is preferable from the viewpoint of reaction yield. Considering these, in practice, the reaction temperature is room temperature to 300 ° C., and the reaction time is 0.5 to 100 hours.

(Examples) Hereinafter, the present invention will be described more specifically with reference to Examples and Comparative Examples.

Example 1 1000 g of anisole as an organic solvent was placed in a glass flask equipped with a reflux condenser and equipped with a stirrer and having a volume of 2 l, and 517 g of zinc fluoride (10.0 equivalents) was added and suspended. In addition, 473 g of 2-chloronitrobenzene
After (3.0 equivalents) was added, the flask was heated and reacted at the reflux temperature of anisole (about 154 ° C.) for 8 hours. After the completion of the reaction, the contents of the flask were filtered to remove the produced solid matter consisting of zinc chloride and unreacted zinc fluoride, and then the filtrate was separated by distillation to obtain 208 g of 2-fluoronitrobenzene as a product (yield). Rate 49%).

Example 2 800 g of toluene as an organic solvent was added to the apparatus used in Example 1.
Then, 310 g (6.0 equivalents) of zinc fluoride was added and suspended. To this, 281 g (2.0 equivalents) of benzoyl chloride was added and reacted at room temperature for 12 hours. After completion of the reaction, the contents of the flask were filtered to remove solids in the same manner as in Example 1,
The filtrate was distilled and separated to obtain 170 g of a product, benzoyl fluoride (yield 71%).

Comparative Example 1 1000 g of tetramethyl sulfone, which is a polar solvent, was added as an organic solvent to the apparatus used in Example 1, and 290 g (10.0 equivalents) of Spray Dry KF (Morita Chemical Co., Ltd.) was added as a fluorinating agent to the suspension. Let After further adding 743 g (3.0 equivalents) of 2-chloronitrobenzene, the flask was heated and reacted at 200 ° C for 8 hours. After the completion of the reaction, the contents of the flask were filtered to remove solids in the same manner as in Example 1, and the filtrate was distilled off. As a result, only 30 g of 2-fluoronitrobenzene as a product was obtained (yield 7
%).

Comparative Example 2 800 g of acetonitrile as an organic solvent was placed in the apparatus used in Example 1, and 174 g (6.0 equivalents) of Supray Dry KF (manufactured by Morita Chemical Co., Ltd.) was added thereto and suspended. Further, 281 g (2.0 equivalents) of benzoyl chloride was added and reacted at room temperature for 12 hours. After completion of the reaction, the contents of the flask were filtered to remove solids in the same manner as in Example 1, and then the filtrate was separated by distillation. The yield of the product benzoyl fluoride was 134 g.
(Yield 36%), which was a low yield compared to the examples.

(Effects of the Invention) As described in detail above, an aprotic apolar solvent is used as an organic solvent to react an organic compound having an active chloro group and / or a bromine group with zinc fluoride to give an organic fluorine compound. According to the present invention for producing, the organic fluorine compound as the target product can be obtained in a much higher yield by a conventionally known method, as shown in Examples and Comparative Examples.

Further, in the conventionally known method, a polar solvent had to be used, but in the method of the present invention, an inexpensive nonpolar solvent is used as described above, and in this respect, the industrial significance is great. There is something.

Claims (1)

[Claims] 1. A method for producing an organic fluorine compound, which comprises reacting an organic compound having an active chloro group and / or a bromine group with zinc fluoride in an aprotic apolar organic solvent.