JP2002284709A - Method for producing organic fluorine compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for safely producing an organic fluorine compound at a low cost, which eliminates the defects of conventional methods. SOLUTION: This method for safely producing the organic fluorine compound is characterized by using both a diaminodifluoromethane compound represented by formula (A) (R1 , R2 , R3 , and R4 are each identically or differently H or a 1 to 20C residue) and an organic heterogeneous atom oxide-based oxidizing agent. Thereby, the organic fluorine compound can safely be produced as one of fluorine gas alternative methods at a low cost.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing an organic fluorine compound.

[0002]

2. Description of the Related Art Organic fluorine compounds are extremely useful for functional materials such as medicines, agricultural chemicals and liquid crystals, and organic fluorine compounds have been actively researched and developed in recent years. On the other hand, as a method for producing these organic fluorine compounds, methods, and methods of using a fluorinating agent prepared from these are typical according to the method, an alkali metal fluoride salts such method, according to the hydrogen fluoride by the fluorine gas . In particular, the method using fluorine gas and the method using hydrogen fluoride are known as highly reactive and low-cost methods.However, these methods have high toxicity themselves and low boiling point to outside the system. Special equipment is required due to the ease of leakage, and both are usually not easy to handle. However, when comparing the two strictly, toward hydrogen fluoride, gentle reaction proceeds, and for lower vapor pressure, over easy to handle is safe, as an alternative, more reactive than hydrogen fluoride Relatively inexpensive nucleophilic fluorinating agents are being developed, and problems such as safety have been almost solved.

On the other hand, a method using a fluorine gas, after the fluorination reaction itself is very vigorous itself is a gas state, is clearly dangerous than in the case of hydrogen fluoride. Normally, fluorine gas is diluted with an inert gas such as nitrogen to about 5 to 10% to reduce reactivity, and further, about 100 to-
Although a special method such as a gradual blowing reaction at an extremely low temperature of 50 ° C. is used, it can be said that the risk is still high. As an alternative to fluorine gas, there is a method using an electrophilic fluorinating agent, but unfortunately it is still expensive, there are still problems such as the recovery of counter ions, and the yield may not be high. Except in some cases, it is not enough. That is, there has been a strong demand for the development of a fluorine gas alternative method that can produce an organic fluorine compound more safely and at lower cost.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a safer and less expensive method for producing an organic fluorine compound which has solved the drawbacks of the conventional method for producing an organic fluorine compound.

[0005]

DISCLOSURE OF THE INVENTION In view of the above problems, the present inventors have conducted intensive studies on a method for producing an organic fluorine compound. As a result, surprisingly, the corresponding urea was added to a halogenating agent such as phosgene. To form a haloimidazolinium salt, and then a diaminodifluoromethane having a specific structure obtained by reacting a metal fluoride such as potassium fluoride with an oxidizing agent. have found that it is an alternative to gas. Furthermore, as a result of examining the oxidizing agent, usually, peroxide, oxygen, metal oxide,
After finding that the yield tends to decrease with oxidizing agents such as nitric acid and nitrate directly acting on oxygen atoms, the results of further investigation show that when an organic heteroatom oxide oxidizing agent is used, the oxygen atom There found that improved specifically yields in the oxidizing agent to act, have reached the present invention.

That is, the present invention relates to a compound represented by the formula (A):

[0007]

Embedded image (Wherein, R ₁ , R ₂ , R ₃ , and R ₄ may be the same or different and each represents a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms). This is a method for producing an organic fluorine compound, which comprises using methanes and an oxidizing agent in combination.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
The present invention is a method for producing an organic fluorine compound using a diaminodifluoromethane having a specific structure represented by the formula (A) in combination with an organic heteroatom oxide-based oxidizing agent. Diaminodifluoromethanes represented by the formula (A) are disclosed in
As described in JP-A-38370, it is obtained by reacting a corresponding urea with a halogenating agent such as phosgene to form a haloimidazolinium salt and then reacting with a metal fluoride salt such as potassium fluoride. .

R ₁ , R ₂ , R ₃ and R ₄ in the formula (A) may be the same or different and represent a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms. A hydrocarbon group of 10 is relatively preferred, and a hydrocarbon group of 1 to 6 carbon atoms is more preferred.

Specifically, for example, hydrogen, methyl, trifluoromethyl, ethyl, trifluoroethyl, perfluoroethyl, n-propyl, isopropyl, perfluoropropyl, n-butyl , Isobutyl group, t-butyl group, perfluorobutyl group, n-
Pentyl group, isopentyl group, cyclopentyl group, n-
Hexyl, isohexyl, cyclohexyl, phenyl, benzyl, methylphenyl, ethylfell, isopropylphenyl, n-propylphenyl, ibutylphenyl, t-butylphenyl, dimethylphenyl, diethylfell , Diisopropylphenyl group, di-n-propylphenyl group, dibutylphenyl group, di-t-butylphenyl group, trimethylphenyl group, triethylfell group, trisopropylphenyl group, tri-n-propylphenyl group, triisobutylphenyl Group, tri-t-butylphenyl group, fluorophenyl group, difluorophenyl group, trifluorophenyl group, chlorophenyl group, dichlorophenyl group, trichlorophenyl group, bromophenyl group, dibromophenyl group, tribromophenyl group Group, a biphenyl, and the like,
Among them, methyl group, trifluoromethyl group, ethyl group, trifluoroethyl group, perfluoroethyl group, n
- propyl group, an isopropyl group, a perfluoropropyl group, n- butyl group, an isobutyl group, t- butyl group, a cyclohexyl group, more preferred if the phenyl group, the present invention is not limited only to these exemplified compounds is not.

The diaminodifluoromethanes represented by the formula (A) include, for example, bis (dimethylamino) difluoromethane, bis (diethylamino) difluoromethane, bis (N-methyl-N-phenyl) difluoromethane and the like. It is exemplified, but the present invention is not limited only to these exemplified compounds.

[0012] fluorinated amount of diamino-difluorobenzyl methanes used in the reaction include, but not be particularly limited because vary greatly depending on the reaction conditions, the range of 1 to 20 equivalents relative to approximately the raw material with a fluorine atom in terms, preferably Is in the range of 1 to 10 equivalents, more preferably in the range of 2 to 5 equivalents. 20 the reaction may be carried out in an equivalent or higher tend to volumetric efficiency deteriorates. These diaminodifluoromethanes may be used alone or in combination of two or more.

The organic heteroatom oxide oxidizing agent used in combination with the diaminodifluoromethanes of the formula (A) refers to an oxygen atom bonded to a heteroatom other than carbon, hydrogen and oxygen among the atoms constituting an organic compound. it is an organic compound of the form. Such heteroatoms include, for example, nitrogen, sulfur, selenium, tellurium, tin, silicon, phosphorus, arsenic, boron, zinc,
Atoms such as lead, titanium and the like may be mentioned, but more specifically, nitrogen and sulfur atoms among them may give relatively favorable results.

More specific examples of the organic heteroatom oxide oxidizing agent include N-hydroxyimide compounds such as N-hydroxysuccinimide and N-hydroxyphthalimide, and pyridine-N-oxide. , 2,6-lutidine -N- oxide, 2,4,6
Examples include aromatic N-oxide compounds such as trimethylpyridine-1-oxide, sulfoxide compounds such as diphenylsulfoxide and dimethylsulfoxide, and sulfone compounds such as diphenylsulfone, but the present invention is limited to only these exemplified compounds. Not something.

[0015] The amount of the organic heteroatom oxide-based oxidizing agent, can not particularly limited because vary greatly depending on the reaction conditions, 1 to 10 equivalents of range for approximately raw material, preferably 1 to 5 equivalent weight ranging, further Preferably 2
3 is in the range of equivalents. These organic heteroatom oxide-based oxidizing agents may be used alone or in combination of two or more.

The process for producing an organic fluorine compound using a diaminodifluoromethane having a specific structure represented by the formula (A) and an organic heteroatom oxide oxidizing agent according to the present invention is described below.
If some of them are explained with examples, for example, an addition reaction to an olefin, a hydrogen-substituted fluorination reaction of an aromatic ring, a fluorination reaction of a hydrazone and the like can be mentioned. Further, the manufacturing methods thereof will be described in more detail sequentially, but the present invention is not limited to only these manufacturing examples.

The addition reaction to an olefin is a reaction of adding a halogen atom such as a fluorine atom to an unsaturated group.
Unsaturated compounds such as styrene and cyclohexene are reacted with bis (dimethylamino) difluoromethane as diaminodifluoromethanes and N-hydroxysuccinimide as an organic heteroatom oxide-based oxidizing agent. This is a reaction for synthesizing 2-difluoro-ethyl) benzene. In this case, the use amount of diaminodifluoromethanes is about 2 to 5 times mol (based on styrene), and the use amount of the organic heteroatom oxide oxidizing agent is 2 to 5 times.
About 5 times mol (to styrene), reaction temperature is about -10 to 2
5 ° C.

The hydrogen-substituted fluorination reaction of the aromatic ring is carried out, for example, by adding 2,3-lutidine N-oxide as an organic heteroatom oxide-based oxidizing agent to phenol in an amount of 2 to 3 times mol (to phenol) at 30 to 50 ° C. For 0.5 to 1 hour, then add bis (dimethylamino) difluoromethane in an amount of 5 to 20 times mol (relative to phenol), and further react at the same temperature for 0.5 to 2 hours.
This is a reaction in which 4-fluorophenol is obtained by performing a catalytic reduction reaction with hydrogen using a noble metal catalyst such as platinum carbon.

The fluorination reaction of hydrazones is a reaction for breaking a carbon-nitrogen double bond to introduce a fluorine atom. For example, a hydrazone synthesized by reacting hydrazine with a ketone is added with a large excess (5 to 50 times mol (vs hydrazone)) of bis (dimethylamino) difluoromethane and an organic heteroatom oxide-based oxidizing agent, to 1
This is a reaction in which 0-fold moles (relative to hydrazones) of N-hydroxysuccinimide is added at a reaction temperature of about -100 to 0 ° C. and reacted to obtain difluoromethylene compounds.

As the reaction solvent, an aliphatic halogenated solvent such as methylene chloride, dichloroethane or chloroform is relatively preferably used in any case. However, even if diaminodifluoromethanes are used as the solvent as they are, preferable results can be obtained. there is a case to give.

In the production method of the present invention, the above-mentioned diaminodifluoromethanes, organic heteroatom oxide-based oxidizing agents and solvents are used for the purpose of controlling the reaction rate and improving the reaction results. In addition, various compounds can be added within a range that does not cause a problem. For example, hydrochloric acid, hydrofluoric acid, sulfuric acid, fluoromethyl sulfate, phosphoric acid, acetic acid, boric acid, boron trifluoride, trifluoromethanesulfonic acid, sodium hydroxide, sodium carbonate, triethylamine, pyridine, triphenylphosphine,
Sodium acetate, an organic or an acid or base, potassium fluoride inorganic potassium phosphate, etc., sodium fluoride, sodium bromide, metal halides such as potassium iodide, long chain alkyl (aryl) sulfonic acid alkali metal salts, tetra Examples thereof include an interlayer transfer catalyst such as an alkyl (aryl) ammonium halide or a surfactant, a solvent, an additive, and a catalyst other than those described above. Further, in the present invention, it may be more preferable to carry out the reaction in the presence of an inert gas such as nitrogen.

It is relatively desirable that the material of the reactor is not glass, and it is more preferable to use a resin such as Teflon (registered trademark) and polyolefin, and an acid-resistant metal such as Hastelloy. The thus obtained organic fluorine compound according to the present invention is an organic compound having at least one fluorine atom in its molecule, and is extremely useful for functional materials such as medicines, agricultural chemicals and liquid crystals.

[0023]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 A reaction flask equipped with a condenser was charged with 41.1 g (0.50 mol) of the starting materials cyclohexene, 172.7 g (1.25 mol) of bis (dimethylamino) difluoromethane,
After carefully charging 1000 ml of methylene chloride, 86.32 g of N-hydroxysuccinimide as an organic heteroatom oxide-based oxidizing agent is added with good stirring.
The (0.75 mol) was added slowly at 0 ° C., and reacted for 2 hours with stirring maintained at the same temperature. After cooling, the obtained reaction solution was gradually neutralized with aqueous sodium carbonate, and then the residue obtained by concentration under reduced pressure with an evaporator was filtered. The filter cake was further washed with N, N'-dimethylimidazolidinone. Finally, vacuum distillation together filtrate and washings 98% pure 1,2-difluoro - give cyclohexane 65.2 g (56% yield).
Incidentally, the reaction system was carried out under nitrogen atmosphere.

Comparative Example 1 A test was conducted in the same manner as in Example 1 except that lead dioxide was used as an oxidizing agent. As a result, the yield of 1,2-difluoro-cyclohexane was 10%.

[0026]

According to the present invention, an organic fluorine compound can be produced safely and relatively inexpensively as one of the fluorine gas substitution methods.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Naoki Asashige 580-32 Nagaura, Sodegaura-shi, Chiba F-term in Mitsui Chemicals, Inc. 4H006 AA02 AC30 BB12 BE90

Claims (6)

[Claims] 1. A compound of the formula (A) (Wherein, R ₁ , R ₂ , R ₃ , and R ₄ may be the same or different and each represents a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms). A method for producing an organic fluorine compound, comprising using methanes and an organic heteroatom oxide-based oxidizing agent in combination. 2. An organic heteroatom oxide-based oxidizing agent,
2. The production method according to claim 1, wherein the production method is an N-hydroxyimide compound, an aromatic N-oxide compound, a sulfoxide compound, or a sulfone compound. 3. An organic heteroatom oxide-based oxidizing agent comprising N
2. The production method according to claim 1, which is -hydroxysuccinimide or N-hydroxyphthalimide. 4. The method according to claim 1, wherein the organic heteroatom oxide oxidizing agent is pyridine N-oxide, 2,6-lutidine N-oxide, or 2,4,6-trimethylpyridine-1-oxide. 5. The method according to claim 1, wherein the organic heteroatom oxide-based oxidizing agent is diphenylsulfoxide. 6. The method according to claim 1, wherein the organic heteroatom oxide-based oxidizing agent is diphenyl sulfone.