JP2002284720A - 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 producing the organic fluorine compound is characterized by using both a urea hydrofluoride compound represented by formula (A) (R1 , R2 , R3 , and R4 are each identically or differently H or a 1 to 20C hydrocarbon group) and an oxidizing agent. Thereby, the organic fluorine compound can safely be produced at a low cost as one of fluorine gas alternative methods.

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]

Means for Solving the Problems In view of such problems, the present inventors have conducted intensive studies on a method for producing an organic fluorine compound, and surprisingly found that hydrogen fluoride gas was charged into urea. The present inventors have found that if the urea hydrogen fluoride salt having a specific structure obtained as described above is used in combination with an oxidizing agent, fluorine gas can be replaced at a relatively low cost, and the present invention has been achieved.

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

[0007]

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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. The method for producing an organofluorine compound is characterized in that a urea hydrogen fluoride represented by the formula (1) is used in combination with an oxidizing agent.

[0009]

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 urea hydrofluoride having a specific structure represented by the formula (A) in combination with an oxidizing agent.

The urea hydrofluoride represented by the formula (A) is
It can be easily obtained simply by charging hydrogen fluoride to the corresponding ureas.

R ₁ , R ₂ , R ₃ , and R in the formula (A)
₄ may be the same or different and each represents a hydrogen atom or 1 carbon atom;
It represents a hydrocarbon group having from 1 to 20 carbon atoms, preferably a hydrocarbon group having 1 to 10 carbon atoms, and more preferably a hydrocarbon group having 1 to 6 carbon atoms. Specifically, for example, hydrogen, methyl group, trifluoromethyl group, ethyl group, trifluoroethyl group, perfluoroethyl group, n-propyl group, isopropyl group, perfluoropropyl group, n-butyl group, isobutyl group , T-butyl group, perfluorobutyl group, n-pentyl group, isopentyl group, cyclopentyl group, n-hexyl group, isohexyl group, cyclohexyl group, phenyl group, benzyl group, methylphenyl group, ethylfell group, isopropylphenyl group, n-propylphenyl group, ibutylphenyl group, t-butylphenyl group, dimethylphenyl group, diethylfell group, diisopropylphenyl group, di-n-propylphenyl group, diibutylphenyl group, di-t-butylphenyl group, Trimethylphenyl, triethylfel, tri Propylphenyl group, tri -n- propyl phenyl group, tri-isobutylphenyl group, tri -t- butylphenyl group, fluorophenyl group, difluorophenyl group, trifluorophenyl group, chlorophenyl group, dichlorophenyl group,
Trichlorophenyl group, bromophenyl group, dibromophenyl group, tribromophenyl group, biphenyl and the like, among which methyl group, trifluoromethyl group,
Ethyl, trifluoroethyl, perfluoroethyl, n-propyl, isopropyl, perfluoropropyl, n-butyl, isobutyl, t-butyl, cyclohexyl, and phenyl are more preferred. However, the present invention is not limited only to these exemplified compounds. In addition, the number n of hydrogen fluoride acting on ureas represents a number exceeding 0, and naturally includes a number below the decimal point. Typically, in the range of approximately 0.10 to 30.00, preferably in the range of 2.00 to 25.00, more preferably the range of 5.00 to 20.00.

The amount of the urea hydrofluoride used in the fluorination reaction varies greatly depending on the reaction conditions, and thus is not particularly limited. Preferably 1 to
The range is 10 equivalents, more preferably 1 to 5 equivalents. 20 the reaction may be carried out in an equivalent or higher tend to volumetric efficiency deteriorates. Also, these urea hydrogen fluoride salts
One or more of them may be used.

The oxidizing agent used in combination with the urea hydrofluoride having the specific structure represented by the formula (A) is directly affected by oxygen atoms such as peroxides, oxygen, metal oxides, nitric acid and nitrates. Such an oxidizing agent may reduce the yield. Oxidizing agents in which oxygen atoms do not act directly have relatively low yields, for example, halogens other than fluorine,
N-haloimides, alkyl (aryl) fluorosulfate
Or fatty acid group IVa metal salts.

More specifically, these may be exemplified by halogens other than fluorine such as chlorine, bromine and iodine, N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, N-chlorophthalate. acid imide, N- bromophthalic acid imide, N- Yodofutaru acid imide, 1,1-dichloro-5,5-dimethylhydantoin, 1,1-dibromo-5,5-dimethylhydantoin, or 1,1-diiodo -5, N-haloimides such as 5-dimethylhydantoin; alkyl (aryl) sulfates such as methyl fluorosulfate, trifluoromethyl fluorosulfate, ethyl fluorosulfate and phenyl fluorosulfate; lead acetate, lead propionate, tin acetate, and propionic acid fatty acids IVa group metal salts such as tin and the like, and the present invention is this It is not limited only to the listed compounds.

The amount of these oxidizing agents varies greatly depending on the reaction conditions, and is not particularly limited. It is in the equivalent range. Also,
These oxidizing agents may be used alone or in combination of two or more.

A part of the method for producing an organic fluorine compound of the present invention, which uses a urea hydrofluoride having a specific structure represented by the formula (A) and an oxidizing agent, will be partially described with reference to examples. Examples thereof include an addition reaction to an olefin, a hydrogen-substituted fluorination reaction of an aromatic ring, a desulfurization fluorination reaction, a fluorination reaction of hydrazones, and the like. 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.
In the case of styrene, an unsaturated compound such as styrene or cyclohexene is reacted with N, N, N ', N'-tetramethylurea hydrofluoride as urea hydrofluoride and N-iodosuccinimide as oxidant. Then (2-iodo-1
-Fluoro-ethyl) benzene. In this case, the amount of urea hydrofluoride used is about 1 to 5 times mol (based on styrene) as hydrogen fluoride, the amount of oxidizing agent used is about 1 to 5 times mol (based on styrene), and the reaction temperature is about 10 to 10 times. 25 ° C.

The hydrogen-substituted fluorination reaction of the aromatic ring is carried out, for example, by adding lead acetate as an oxidizing agent to phenol in an amount of 2 to 3 moles (relative to phenol) and stirring the mixture at 30 to 50 ° C. for 0.5 to 1 hour. N, N, N ', N'-tetramethylurea hydrofluoride is added 5 to 20 times mol (relative to phenol), and the mixture is further reacted at the same temperature for 0.5 to 2 hours to give 4,4, -difluoro- This is a reaction for synthesizing cyclohexadien-1-one. The 4,4, -difluoro-cyclohexadien-1-one obtained here can be easily converted to 4-fluorophenol by performing a catalytic reduction reaction with hydrogen using a noble metal catalyst such as platinum carbon in an alcoholic solvent. Obtainable. The desulfurization fluorination reaction is a reaction in which a carbon-sulfur bond is cleaved to introduce a fluorine atom. For example, thioethers, thiols, and fluorinated from dithiocarbonate like, difluoromethyl of the thiocarbonyl and dithio acetal, trifluoromethylation from ortho thioester and a dithiocarboxylate ester or the like, dithiocarbonate and (difluoro - methylthio - methyl) - (alkyl) - trifluoromethyl etherification, etc. from ether.

More specifically, for example, dithiocarbonates synthesized from alcohol, carbon disulfide and alkyl halides such as methyl iodide in the presence of a strong base such as sodium hydride include: Large excess $ 10-1
00 times mole (based on dithiocarbonates)} N, N,
N ', N'-tetramethylurea hydrofluoride and 2 to 10 moles (as opposed to dithiocarbonate) of N as an oxidizing agent
Bromosuccinimide at a reaction temperature of about 20-20.
The reaction is performed by adding at ℃ and reacting to obtain a corresponding trifluoromethyl ether compound.

The fluorination reaction of hydrazones is a reaction in which a carbon-nitrogen double bond is cleaved to introduce a fluorine atom. For example, a hydrazone synthesized by reacting a hydrazine with a ketone is added with a large excess of N, N, N ′, N′-tetramethylurea hydrofluoride in a 5- to 50-fold molar amount (relative to the hydrazone). A reaction in which 2 to 10 times the molar amount of N-bromosuccinimide (relative to hydrazone) as an oxidizing agent is added at a reaction temperature of about 100 to 0 ° C. to obtain a difluoromethylene compound. As the reaction solvent, in each case, an aliphatic halogen-based solvent such as methylene chloride, dichloroethane, and chloroform is relatively preferably used, but a preferable result may be obtained even when urea hydrogen fluoride is used as the solvent as it is. is there.

In the production method of the present invention, in addition to the above-mentioned urea hydrofluoride, oxidizing agent and solvent, for the purpose of adjusting the reaction rate and improving the reaction results, etc.
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,
Organic or inorganic acids or bases such as trifluoromethanesulfonic acid, sodium hydroxide, sodium carbonate, triethylamine, pyridine, triphenylphosphine, sodium acetate, potassium phosphate, potassium fluoride, sodium fluoride, sodium bromide, iodide Interlayer transfer catalysts or surfactants such as metal halides such as potassium, alkali metal salts of long-chain alkyl (aryl) sulfonic acids, and tetraalkyl (aryl) ammonium halides, solvents, additives, catalysts and the like other than those described above Is mentioned. Further, in the present invention, it is more preferable to carry out the reaction in the presence of an inert gas such as nitrogen. The material of the reactor is desirably non-glass for the purpose of preventing corrosion, and resins such as Teflon (registered trademark) and polyolefin, and acid-resistant metals such as Hastelloy are relatively preferable.

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 In a reaction flask equipped with a condenser, 41.1 g (0.50 mol) of the starting material cyclohexene, N, N, N ', N'-
Tetramethylurea 10 (hydrogen fluoride) salt 72.7 (0.
After carefully charging 1000 ml of methylene chloride, 168.7 g (0.75 mol) of N-iodosuccinimide as an oxidizing agent was added while stirring well.
C., and the mixture was stirred and maintained at the same temperature for 2 hours to react. After cooling, the obtained reaction solution was gradually neutralized with aqueous sodium carbonate, and then the remaining solution concentrated under reduced pressure by an evaporator was filtered, and the filter cake was further washed with methylene chloride.
Finally, the filtrate and the washing solution were combined and distilled under reduced pressure to obtain 98% pure 1
-Fluoro-2-iodo-cyclohexane by 101.2
g (yield 87%). Incidentally, the reaction system was carried out under nitrogen atmosphere.

Comparative Example 1 Pyridine 10 (hydrogen fluoride) salt was used instead of N, N, N ', N'-tetramethylurea 10 (hydrogen fluoride) salt, and lead dioxide was used as an oxidizing agent. Was tested in the same manner as in Example 1. As a result, 1-fluoro-2-iodo-
The yield of cyclohexane was 41%.

[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.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Ryoichi Seki 580-32 Nagaura, Sodegaura-shi, Chiba F-term in Mitsui Chemicals, Inc. 4H006 AA02 AC30 BA50 BA51 BA52 BB11 BC10 BC31 BE53

Claims (5)

[Claims] 1. A compound of the formula (A) (In the formula, 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. N represents a number exceeding 0. A method for producing an organic fluorine compound, comprising using a urea hydrogen fluoride salt represented by the formula (1) and an oxidizing agent in combination. 2. The method according to claim 1, wherein the oxidizing agent is chlorine, bromine, iodine, N-haloimides, alkyl (aryl) fluorosulfates, or fatty acid IVa metal salts. 3. The method according to claim 1, wherein the oxidizing agent is N-chlorosuccinimide,
- bromosuccinimide, N- iodosuccinimide,
N-chlorophthalimide, N-bromophthalimide, N-iodophthalimide, 1,1-dichloro-
5,5-dimethylhydantoin, 1,1-dibromo-
2. The method according to claim 1, wherein the production method is 5,5-dimethylhydantoin or 1,1-diiodo-5,5-dimethylhydantoin. 4. The method according to claim 1, wherein the oxidizing agent is methyl fluorosulfate. 5. The method according to claim 1, wherein the oxidizing agent is lead acetate.