JPH10218826A - Production of 4-fluoro-3-phenoxybromobenzene - Google Patents

Abstract

PROBLEM TO BE SOLVED: To inexpensively obtain the subject compound which is a raw material intermediate for a bromide useful as a raw material for an insecticide by reacting 4-fluoro-3-phenoxyaniline with a diazotizing agent and further reacting the reaction product with a bromine compound in the presence of a chopper salt. SOLUTION: N,N-Dimethylformamide is reacted with phosgene, then with 3-chloro-4-fluoroaniline and treated with a hydroxide to give N-(3-chloro-4- fluorophenyl)-N',N'-dimethylformamidine, which is reacted with an alkali metal salt of phenol in the presence of metal cooper and/or a copper salt in a solventless state or in an organic solvent to give N-(4-fluoro-3-phenoxyphenyl)-N', N'-dimethylformamidine. This compound is incorporated with hydrazine hydrate and an alcohol, a dimethylformamidine group is deprotected to give 4-fluoro-3- phenoxyaniline, which is diazotized in a solvent and the prepared reaction product is reacted with a bromine compound in the presence of a copper salt to give the objective compound.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing 4-fluoro-3-phenoxybromobenzene. The 4-fluoro-3-phenoxybromobenzene obtained by the present invention has the general formula 1 having insecticidal activity.

[0002]

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(Where R₁And R_TwoAre the same or different
Hydrogen atom, halogen atom, lower alkyl group,
Oromethyl group, lower alkoxy group, lower alkenyloxy
Represents a silyl group or a halogen-substituted lower alkoxy group;
R₁And R_TwoTogether form a methylenedioxy group
You. R_ThreeRepresents a vinyl group or an ethynyl group. R_FourIs water
Represents an elementary atom or a lower alkyl group. R_FiveIs a hydrogen atom
Or a fluorine atom. R ₆Is a hydrogen atom, a halogen atom
, A lower alkyl group, a lower alkoxy group, or trifluoro
Represents an olomethyl group. Z represents a nitrogen atom or a —CH ＝ group
Y represents an oxygen atom when Z represents a nitrogen atom;
Represents a —CH ＝ group, Y represents an oxygen atom, a sulfur atom,
Represents a len group or a -NH- group. )

[0004] A hydrocarbon compound represented by
-5928) is useful as a production intermediate.

[0005]

2. Description of the Related Art A general formula is disclosed in JP-A-62-25928.
Formula 1 as one of the starting materials of Chemical Formula 1

[0006]

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A bromide represented by the following formula is described. The bromide is derived from 4-fluoro-3-phenoxybenzaldehyde by a Wittig reaction or the like as shown in the following chemical formula 3 (US Pat. No. 4,709,068, US Pat. No. 488).
No. 3789) (Production Example 1),

[0008]

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Alternatively, the reaction may be carried out by increasing the carbon using malonic acid as shown in the following chemical formula (British Patent No. 2187452 A).
1) (Production Example 2) It is synthesized by any of the methods.

[0010]

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As a general method for deprotection of amidine, a method using dilute aqueous ammonia (Colle) has been used.
ct. Czech. Chem. Comm. , 31 ,, 31
98 (1966). ), Using concentrated hydrochloric acid (J. Or.
g. Chem. , 42 , 2639 (1977). ), Potassium hydroxide, water and methanol (J.A.
m. Chem. Soc. 106 , 3270 (198
4). ), Hydrazine, acetic acid, and ethanol (J. Am. Chem. Soc. 106 , 3270 (1)
984). ), A method using lithium aluminum hydride (J. Am. Chem. Soc. 106 , 3270).
(1984). ) And zinc chloride (Syn)
th. Commun. , 24 , 1617 (199
4). ) Etc. are known.

On the other hand, 4-fluoro-3-phenoxybromobenzene is obtained by converting 5-bromo-2-fluoroaniline into 4-bromo-2-iodofluorobenzene as shown in the following formula 5, and subjecting this to Ullmann reaction with phenol. (Japanese Patent Application Laid-Open No. 62-292737)

[0013]

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The 4-fluoro-3-phenoxybromobenzene is converted from 4-fluoro-3-phenoxybenzaldehyde via 4-fluoro-3-phenoxybenzoic acid and 4-fluoro-3-phenoxybenzoyl chloride as shown in the following chemical formula 6. Synthesize (Japanese Unexamined Patent Publication No. 62-29273)
7),

[0015]

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As shown in the following formula 7, 5-bromo-2-fluorophenol is synthesized from 2,4-dibromofluorobenzene via dihydroxy- (5-bromo-2-fluorophenyl) -borane, and this is subjected to Ullmann reaction. It is synthesized by using (JP-A-62-252740).

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[0017]

However, in the above methods, any of the starting compounds, 4-fluoro-
3-Phenoxybenzaldehyde is relatively expensive, and in Production Example 1, eutrophic wastewater is generated from the phosphorus compound used in the Wittig reaction, and in Production Example 2, the phosphorus compound used in the reaction for replacing an alcoholic hydroxyl group with a bromine atom. In addition, both use relatively expensive lithium aluminum hydride to reduce the ester to alcohol, which is not necessarily an industrially preferable method from the viewpoint of economic efficiency and protection of the natural environment. Did not. On the other hand, in the synthesis of the known 4-fluoro-3-phenoxybromobenzene shown in Chemical formulas 5 to 7, any of the methods has a low yield, and furthermore, a relatively expensive iodide,
Ruthenium compounds, boron compounds, and the like are used, and these methods are not necessarily industrially preferable.

In view of such circumstances, the present inventors have intensively studied a method for producing bromide represented by Chemical formula 2 which is inexpensive and does not generate eutrophic wastewater and the like. Using 4-fluoroaniline as a main raw material, 4-fluoro-3-phenoxybromobenzene is obtained by the reaction shown in the following chemical formula 8, and when this is used as an intermediate, it is environmentally friendly such as generation of eutrophic wastewater. The present inventors have found that the bromide represented by the above formula (2) can be obtained without the problems described above and at a relatively low cost in industrial production without any operational problems, and have completed the present invention.

[0019]

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[0020]

That is, the present invention provides 4-
Reacting a fluoro-3-phenoxyaniline with a diazotizing agent in a solvent, and then reacting the resulting reaction product with a bromine compound in the presence of a copper salt.
An object of the present invention is to provide a method for producing 3-phenoxybromobenzene.

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described below in more detail. The present invention provides a method for producing 4-fluoro-3-phenoxybromobenzene, which is useful as a raw material intermediate for bromide represented by the above formula (2).

4-Fluoro-3-phenoxybromobenzene is obtained by reacting 4-fluoro-3-phenoxyaniline with a diazotizing agent in a solvent, and then reacting the obtained reaction product with a bromine compound in the presence of a copper salt. Can be obtained.

4-Fluoro-3-phenoxyaniline is N- (4-fluoro-3-phenoxyphenyl)-
It can be obtained by adding hydrazine hydrate and alcohol to N ′, N′-dimethylformamidine and deprotecting the dimethylformamidine protecting group.

N- (4-fluoro-3-phenoxyphenyl) -N ', N'-dimethylformamidine is
(3-chloro-4-fluorophenyl) -N ', N'-
It can be obtained by reacting dimethylformamidine with an alkali metal salt of phenol in the presence of copper metal and / or copper salt in a solvent-free or organic solvent.

N- (3-chloro-4-fluorophenyl) -N ', N'-dimethylformamidine is N, N
-After reacting dimethylformamide with phosgene,
This was reacted with 3-chloro-4-fluoroaniline,
It can be obtained by treating with a hydroxide.

4-Fluoro-3-phenoxybromobenzene is obtained by reacting N, N-dimethylformamide with phosgene, followed by reacting with 3-chloro-4-fluoroaniline and treating with hydroxide. N- (3-chloro-
4-Fluorophenyl) -N ', N'-dimethylformamidine was obtained and then the resulting N- (3-chloro-4
-Fluorophenyl) -N ', N'-dimethylformamidine and an alkali metal salt of phenol with metallic copper and / or
Or N- (4-fluoro-3-phenoxyphenyl)-by reacting in the absence of a solvent or in an organic solvent in the presence of a copper salt.
N ′, N′-dimethylformamidine was obtained, and the resulting N- (4-fluoro-3-phenoxyphenyl)-
Hydrazine hydrate and alcohols are added to N ′, N′-dimethylformamidine, and the protecting group for dimethylformamidine is deprotected to obtain 4-fluoro-3-phenoxyaniline. It can be obtained by reacting aniline with nitrous acid in a solvent, and then reacting the obtained reaction product with a bromine compound in the presence of a copper salt.

In the above method, the reaction between N, N-dimethylformamide and phosgene is carried out in a suspended state, preferably using a solvent. The solvent is not limited as long as it is inert to the reaction, for example, pentane, hexane, heptane, petroleum ether, aliphatic hydrocarbons such as ligroin, benzene, toluene, aromatic hydrocarbons such as xylene , Dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,1
Halogenated hydrocarbons such as trichloroethane, 1,1,2-trichloroethylene, 1,1,2,2-tetrachloroethylene, chlorobenzene, o-dichlorobenzene, and chlorofluorocarbon, diethyl ether, diisopropyl ether, diphenyl ether, ethylene glycol dimethyl ether, diethylene glycol Examples thereof include ethers such as dimethyl ether and triethylene glycol dimethyl ether, and N, N-dimethylformamide. It is also possible to mix these solvents.

[0028] The reaction temperature is selected from the range of about 0 ° C to about 70 ° C, preferably about 20 ° C to about 50 ° C. When the temperature is lower than about 0 ° C., the reaction hardly proceeds.
The exothermic decomposition of the complex formed from dimethylformamide and phosgene;

The reaction time varies depending on the amount of the reactants and the reaction temperature, and is not unique. However, the reaction for synthesizing a complex from N, N-dimethylformamide and phosgene is usually about 30 minutes.
The reaction of the complex with 3-chloro-4-fluoroaniline may be selected from a range of usually about 30 minutes to about 24 hours.

In carrying out the above method, the amount of N, N-dimethylformamide used is about 1 to about 2 moles, preferably about 1 to about 2 moles, per mole of 3-chloro-4-fluoroaniline.
It is in the range of about 1.5 mole. Even if the amount used is larger than this, no improvement in yield corresponding to that is seen.

On the other hand, the amount of phosgene used is 3-chloro-4
-About 1 to about 2 mol, preferably about 1 to about 1.5 mol, per 1 mol of fluoroaniline. Even if the amount used is larger than this, no improvement in yield corresponding to that is seen. It is preferable that the amount of phosgene used does not exceed the number of moles of N, N-dimethylformamide used. If it exceeds, N- (3-chloro-4-fluorophenyl) carbamoyl chloride and N, N'-bis (3-chloro-4-fluorophenyl) urea are by-produced to produce N- (3-chloro- The purity of 4-fluorophenyl) -N ', N'-dimethylformamidine may be reduced.

The finished product of the complex and 3-chloro-4-fluoroaniline is then treated with a hydroxide. The hydroxide used in the practice of the present invention is not particularly limited as long as it has a function of a dehydrochlorinating agent, and usually includes sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide and the like. Can be

The amount of the hydroxide used is in the range of about 2 to about 4 mol, preferably about 2.5 to about 3.5 mol, per 1 mol of 3-chloro-4-fluoroaniline. If the amount used is larger than this, hydrolysis occurs and N- (3-chloro-4-fluorophenyl) formamide is by-produced, and the yield decreases.

The reaction is carried out usually at a temperature of about 0 ° C. to about 50 ° C., preferably about 20 ° C. to about 40 ° C., and the reaction time may be generally selected from the range of about 30 minutes to about 24 hours.

After the completion of the reaction, N- (3-)
Chloro-4-fluorophenyl) -N ′, N′-dimethylformamidine can be obtained. The N- (3-chloro-4-fluorophenyl) -N ′, N′-dimethylformamidine can be further purified as it is or, if necessary, by means such as recrystallization and column chromatography.

The N- (3-chloro-4-fluorophenyl) -N ', N'-dimethylformamidine thus obtained is free of phenol in the presence of an alkali metal salt of phenol and copper metal or copper salt. React in a solvent or organic solvent, N-
(4-fluoro-3-phenoxyphenyl) -N ′,
N′-dimethylformamidine can be obtained.

The alkali metal of phenol includes sodium salts and potassium salts, and more specifically, sodium phenoxide, potassium phenoxide and the like. Copper salts used in the reaction include cuprous chloride, cupric chloride, cuprous bromide, cupric bromide, cuprous oxide, cupric oxide and the like.

The amount of the alkali metal salt of phenol used is N
-(3-chloro-4-fluorophenyl) -N ', N'
In the range of about 1 to about 2 moles, preferably about 1 to about 1.5 moles per mole of dimethylformamidine. Even if the amount used is larger than this, no improvement in yield corresponding to that is seen.

The amount of metallic copper or copper salt used is N- (3-
(Chloro-4-fluorophenyl) -N ', N'-dimethylformamidine per mole of about 0.01 to about 0.1
Mole, preferably in the range of about 0.03 to about 0.05 mole. Even if the amount used is larger than this, no improvement in yield corresponding to that is seen.

The reaction between N- (3-chloro-4-fluorophenyl) -N ', N'-dimethylformamidine and an alkali metal salt of phenol is carried out in a suspension state, preferably using a solvent. . Examples of the solvent include ethers such as diethylene glycol dimethyl ether and triethylene glycol dimethyl ether. Also,
These solvents may be used as a mixture. The reaction is preferably performed under anhydrous conditions. If water is present, the reaction may not proceed.

The reaction temperature is selected from the range of about 140 to about 170 ° C, preferably about 145 to about 165 ° C. 14
When the temperature is lower than 0 ° C., the reaction hardly proceeds.

The reaction time varies depending on the amount of the reactants and the reaction temperature and is not unique, but may be usually selected from the range of about 12 hours to about 60 hours.

After completion of the reaction, N- (4-fluoro-3-phenoxyphenyl) -N-N was obtained by performing a usual operation such as adding water, removing metallic copper or a copper salt by filtration, extracting with an organic solvent, and concentrating. ', N'-Dimethylformamidine can be obtained. The N- (4-fluoro-3-phenoxyphenyl) -N ′, N′-dimethylformamidine can be further purified as it is or, if necessary, by means such as recrystallization and column chromatography.

In the above method, the deprotection of the dimethylformamidine protecting group is carried out with hydrazine hydrate and, if necessary, with addition of acetic acid. As a solvent, methanol, ethanol, 1-propanol, 2-propanol, 1-
Alcohols such as butanol and 2-butanol are used. These alcohols can be used as a mixture.

The amount of hydrazine hydrate used is about 1 to about 15 mol, preferably about 2 to about 10 mol, based on N- (4-fluoro-3-phenoxyphenyl) -N ', N'-dimethylformamidine. Moles, more preferably in the range of about 3 to about 8 moles. Even if the amount used is larger than this, no improvement in yield corresponding to that is seen. By-products tend to increase as the amount used decreases.

Although the deprotection reaction proceeds even if acetic acid is not used, it is preferable to use acetic acid because it tends to increase by-products. The amount of acetic acid used is in the range of about 0.5 to about 5 mol, preferably about 1 to about 3 mol, based on N- (4-fluoro-3-phenoxyphenyl) -N ′, N′-dimethylformamidine. is there. Even if the amount used is larger than this, no improvement in yield corresponding to that is seen.

[0047] The reaction temperature is selected from the range of about 60 to about 120 ° C, preferably about 70 to about 100 ° C. About 60 ° C
If it is lower, the reaction is difficult to proceed.

The reaction time varies depending on the amount of the reactants and the reaction temperature and is not unique, but may be usually selected from the range of about 10 minutes to about 24 hours.

4-Fluoro-3-phenoxyaniline is subjected to a diazotization reaction in a solvent, followed by Sandmeyer
By reacting, 4-fluoro-3-phenoxybromobenzene can be obtained. 4-fluoro-3
The diazotization reaction of phenoxyaniline in a solvent is performed using at least one diazotizing agent selected from the group consisting of nitrogen oxides, nitrous acid, nitrite, nitrite, and the like. As a specific example, a method using nitrous acid generated by reacting acid and nitrite, especially sodium nitrite in a solvent, or a method of blowing nitrogen oxides such as nitric oxide and nitrogen dioxide into the solvent Etc. are used.

Examples of the acid used in the diazotization reaction include hydrobromic acid and organic acids such as formic acid, acetic acid and propionic acid. The amount of acid used in the diazotization reaction is 4-fluoro-
It ranges from about 2 to about 15 moles, preferably from about 2.5 to about 5 moles, based on 3-phenoxyaniline. The amount of acid is 2
If the amount is less than the mole, the stability of the resulting diazonium salt becomes poor.

The amount of the diazotizing agent used in the diazotization reaction is 4
The range is from about 1 to about 2 moles, preferably from about 1 to about 1.5 moles, based on -fluoro-3-phenoxyaniline.
Even if the amount used is larger than this, there is no corresponding improvement in yield.

The solvent used in the diazotization reaction is not limited as long as it is inert to the reaction. For example, organic acids such as formic acid, acetic acid and propionic acid, and hydrophilic organic solvents such as N, N-dimethylformamide and dimethylsulfoxide. Solvents. It is also possible to mix these solvents. Although the amount of the solvent to be used is not particularly limited, it is appropriately determined based on the reaction rate, workability, economy and the like.

The reaction temperature of the diazotization reaction is about -10 to about 5
0 ° C, preferably selected from the range of about 0 to about 20 ° C. When the temperature is lower than -10 ° C, the diazotization reaction becomes slow, and when the temperature is higher than 50 ° C, the stability of the diazonium salt deteriorates.

The reaction time of the diazotization reaction depends on the amount of the reactants,
The temperature is different depending on the reaction temperature and is not particularly limited, but may be usually selected from the range of about 10 minutes to about 24 hours.

In the Sandmeyer reaction, a copper salt and a bromine compound, in particular, hydrogen bromide and hydrobromic acid are used. Copper salts used include cuprous bromide and / or cupric bromide. The amount of copper salt used is 4-fluoro-
About 0.5 to about 2 mol based on 3-phenoxyaniline,
Preferably it is selected from the range of about 0.8 to about 1.5 moles. Even if the amount used is larger than this, there is no corresponding improvement in yield.

The amount of the bromine compound used in the Sandmeyer reaction is selected from the range of about 0.5 to about 10 mol, preferably about 1 to about 2 mol, based on 4-fluoro-3-phenoxyaniline. Even if the amount used is larger than this, there is no corresponding improvement in yield.

The reaction temperature of the Sandmeyer reaction is about 0.
To about 100C, preferably from about 20C to about 80C. When the temperature is lower than 0 ° C., the reaction rate becomes slow.

The reaction time of the Sandmeyer reaction varies depending on the amount of the reactants and the reaction temperature and is not specifically limited, but may be generally selected from the range of about 10 minutes to 5 hours.

After completion of the reaction, water is added, the mixture is extracted with an organic solvent, and the mixture is subjected to ordinary operations such as concentration to obtain 4-fluoro-3-phenoxybromobenzene as a target substance. The 4-fluoro-3-phenoxybromobenzene can be used as it is or, if necessary, further purified by means of distillation, column chromatography or the like, and used as a raw material for insecticides and the like.

[0060]

According to the present invention, 4-
Fluoro-3-phenoxybromobenzene can be obtained by using relatively inexpensive 3-chloro-4-fluoroaniline as a main raw material, and this can be obtained by using a production method described in Reference Examples described later. The bromide shown in Chemical formula 2, which is useful as a raw material of the insecticide shown in Chemical formula 1, can be obtained without using expensive lithium aluminum hydride as a raw material and without using a phosphorus compound which causes a problem of eutrophic wastewater. It can be manufactured relatively inexpensively, and its industrial utility value is extremely large.

[0061]

Next, 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 2.40 g of 4-fluoro-3-phenoxyaniline
(9.99 mmol) was dissolved in 21.7 g of N, N-dimethylformamide and 2.46 g of acetic acid, and 4.91 g of an aqueous sodium nitrite solution (0.69 g (10.1 mmol as sodium nitrite) was added at 0 to 5 ° C. )) Is dropped and 30
Incubated for a minute. This reaction solution was mixed with 1.98 g (13.8 mmol) of cuprous bromide prepared in another container and 47%
A solution consisting of 2.87 g (16.7 mmol) of aqueous solution of hydrobromic acid was added dropwise at 20 to 30 ° C. or less over 1 hour,
Incubated for hours. After 10 g of water and 20 g of toluene were added thereto, insolubles were removed by filtration, the organic layer was separated, the aqueous layer was extracted with toluene, and the organic layers were combined. The combined organic layers are washed with a 6% aqueous sodium hydrogen carbonate solution and water in this order,
After drying over magnesium sulfate, the magnesium sulfate was filtered off, and the solvent was distilled off under reduced pressure.
4.75 g of black oil (GC purity 49.8%, yield 8)
8.6%). This black oil was purified by distillation to obtain a pale yellow oil [4-fluoro-3-phenoxybromobenzene]. B. p. 147-149 ° C / 4
mmHg.

[0063]

Reference Example 1 (Production Example of 4-Fluoro-3-phenoxyaniline) 60.26 g of N, N-dimethylformamide (0.82
44 mol) was dissolved in 550 g of chlorobenzene and 81.55 g (0.8244 mol) of phosgene were added thereto at 30 ° C.
At a flow rate of 0.6 g / min. 30 ° C after blowing
・ After keeping warm for 30 minutes, 3-chloro-4-fluoroaniline 1
00.00 g (0.6870 mol) of chlorobenzene 1
A solution dissolved in 37 g was added dropwise at 30 ° C. for 1 hour. After keeping the temperature for 1 hour after the dropwise addition, 824.4 g (2.061 mol) of a 10% aqueous sodium hydroxide solution was added dropwise at 25 ° C to 40 ° C. After the temperature was kept at 30 ° C. for 1 hour after dropping, the organic layer was separated, the aqueous layer was extracted with chlorobenzene, and the organic layers were combined. After drying the combined organic layers over anhydrous magnesium sulfate,
Magnesium sulfate was separated by filtration, and chlorobenzene was distilled off under reduced pressure to give pale yellow crystals [N- (3-chloro-4-fluorophenyl) -N ', N'-dimethylformamidine].
135.47 g (GC purity 99.6%, yield 97.9)
%). The obtained pale yellow crystals were recrystallized using a mixed solvent of heptane and toluene to obtain white crystals. M. p. Was 45.1 to 46.1 ° C. (correction value).

The thus obtained N- (3-chloro-4)
-Fluorophenyl) -N ', N'-dimethylformamidine 3.00 g (0.0150 mol), potassium phenoxide 1.98 g (0.0150 mol) and sodium phenoxide 1.74 g (0.0150 mol) in toluene 40 g And 27.0 g of diethylene glycol dimethyl ether were added, and the reaction solution was azeotropically dehydrated until the water content became 1000 ppm or less. Then, 0.08 g (0.0006 mol) of cupric chloride was added to the reaction product after azeotropic dehydration, toluene was distilled off under normal pressure, and the mixture was reacted at 155 ° C. for 24 hours. The area ratio was determined by gas chromatography analysis. Is N-
(4-fluoro-3-phenoxyphenyl) -N ′,
N'-dimethylformamidine / 4-fluoro-3-phenoxyaniline / N- (3-chloro-4-fluorophenyl) -N ', N'-dimethylformamidine / N-
(4-fluorophenyl) -N ′, N′-dimethylformamidine / 4-fluoroaniline = 66.2: 2.
A reaction product of 9: 10.6: 19.8: 0.5 was obtained. Further, diethylene glycol dimethyl ether was distilled off from the reaction product, water was added, and the mixture was extracted with toluene. After drying over anhydrous magnesium sulfate, magnesium sulfate was filtered, toluene was distilled off under reduced pressure, and the residue was dried under vacuum to obtain a black oily substance [yield 3.36 g (GC purity 66.2%, yield 57.6).
%)]. The obtained black oil was purified by silica gel column chromatography to obtain a light brown oil [N- (4-fluoro-3-phenoxyphenyl) -N ', N'-dimethylformamidine]. ¹ H NMR (90 MH
z, δ, CDCl ₃ ) 7.43 to 6.59 (m, 9
H), 2.96 (s, 6H).

The light brown oily substance N-
(4-fluoro-3-phenoxyphenyl) -N ′,
5.00 g of N'-dimethylformamidine (0.019 g)
4 mol) and 7.75 g (0.15 g) of hydrazine monohydrate.
5 mol) and N- (4-fluoro-3-phenoxyphenyl) -N ', N'-dimethylformamidine (8 times mol) were dissolved in 58.07 g of 2-propanol, and the mixture was heated under reflux for 4 hours. After cooling to room temperature, 60.61 g of water
And extracted twice with 58.07 g of dichloromethane.
The extracted organic layers were combined, dried over anhydrous magnesium sulfate, and dichloromethane was distilled off under reduced pressure to obtain an oily substance [crude 4-
Fluoro-3-phenoxyaniline] (4.31 g) was obtained (GC purity: 88.6%, yield: 97.2%). This was purified by silica gel column chromatography, and its physical properties were measured. As a result, ¹ HNMR (90 MHz, δ, CDCl
₃ ) 7.42 to 6.63 (m, 6H), 6.46 to 6.
30 (m, 2H), 3.37 to 3.17 (br, 2H)
Met. Distillation-purified 4-fluoro-3-phenoxyaniline b. p. Is 143 to 146 ° C / 0.2mmH
g.

Reference Example 2 (Production example of bromide represented by Chemical formula 2) 3.79 g of magnesium (0.
156 mol) and 80 g of dry tetrahydrofuran,
A pale yellow oil [4-fluoro-3-phenoxybromobenzene] 4 obtained by the method of Example 1 at 45 ° C.
0.00 g (purity 94.7%, 0.142 mol) and 200 g of dry tetrahydrofuran were added dropwise, and the mixture was stirred at room temperature overnight. 22.31 g of allyl bromide (0.
184 mol) was added dropwise at 60 ° C., and the temperature was kept as it was for 4 hours. After keeping the temperature, 10% ammonium chloride aqueous solution 250g
And extracted three times with 140 g of dichloromethane. The organic layer was washed with 280 g of water, dried over magnesium sulfate,
The magnesium sulfate was filtered, the solvent was distilled off under reduced pressure, and the residue was dried under vacuum to obtain a pale yellow oil. The yield of this is 4
1.19 g, GC purity was 59.4%, and yield was 75.6%. Further, the pale yellow oily substance was purified by distillation. As a result, a colorless oily substance [1-fluoro-2-phenoxy-4-) was obtained.
(2-propenyl) benzene] was obtained. B. p. Was 152 to 155 ° C./5 mmHg.

Then, from 113.51 g of tetralin and 52.14 g of bromine, Inorg. Synth, vol.
Hydrogen bromide gas generated by the method described in 1, page 151 was converted to 19.12 g of 1-fluoro-2-phenoxy-4- (2-propenyl) benzene obtained by the above method.
(Purity 97.4%, 0.082 mol), hexane 57.
4 g, benzoyl peroxide 0.13 g (25% water content, 0.1 g).
0004 mol) and kept warm for 1 hour. To this, 287 g of water was added, the organic layer was separated, and the organic layer was washed sequentially with a 6% aqueous sodium hydrogen carbonate solution, a 10% aqueous sodium sulfite solution, and water. After washing, the extract was dried over anhydrous sodium sulfate, sodium sulfate was filtered, hexane was distilled off under reduced pressure, and the residue was dried under vacuum to obtain 25.5 g of a pale yellow oil (GC purity: 93.8%, yield: 95.1%). ) Got. This was purified by thin-phase chromatography to obtain a colorless oil [1-fluoro-2-phenoxy-4- (3-bromopropyl) benzene] (bromide represented by Chemical Formula 2). ¹
1 H NMR data (90 MHz, δ, CDCl ₃ )
14 (tt, 2H), 2.71 (t, 2H), 3.36
(T, 2H), 6.8-7.5 (m, 8H)

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI C07C 217/90 C07C 217/90 // C07B 61/00 300 C07B 61/00 300 (72) Inventor Teruichi Sugihara Takarazuka-shi, Hyogo 4-2-1 Takashi Sumitomo Kagaku Kogyo Co., Ltd.

Claims (16)

[Claims] 1. A method comprising reacting 4-fluoro-3-phenoxyaniline with a diazotizing agent in a solvent, and then reacting the obtained reaction product with a bromine compound in the presence of a copper salt. A method for producing fluoro-3-phenoxybromobenzene. 2. The 4-fluoro-3- according to claim 1, wherein the diazotizing agent is at least one member selected from the group consisting of nitrogen oxides, nitrous acid, nitrites and nitrites. A method for producing phenoxybromobenzene. 3. The method according to claim 1, wherein the solvent is at least one of organic acids such as formic acid, acetic acid and propionic acid, and hydrophilic organic solvents such as N, N-dimethylformamide and dimethylsulfoxide. Production method of -fluoro-3-phenoxybromobenzene. 4. The solvent according to claim 1, wherein the solvent is at least one of formic acid, acetic acid and propionic acid.
A method for producing fluoro-3-phenoxybromobenzene. 5. The 4-fluoro-phosphate according to claim 1, wherein the copper salt is cuprous bromide and / or cupric bromide.
A method for producing 3-phenoxybromobenzene. 6. The 4-fluoro-3- according to claim 1, wherein the bromine compound is hydrogen bromide or hydrobromic acid.
A method for producing phenoxybromobenzene. 7. The method according to claim 7, wherein 4-fluoro-3-phenoxyaniline is N- (4-fluoro-3-phenoxyphenyl)-
The 4-fluoro compound according to claim 1, which is obtained by adding hydrazine hydrate and alcohols to N ', N'-dimethylformamidine and deprotecting the dimethylformamidine protecting group. A method for producing -3-phenoxybromobenzene. 8. N- (4-fluoro-3-phenoxyphenyl) -N ′, N′-dimethylformamidine is
-(3-chloro-4-fluorophenyl) -N ', N'
8. It is obtained by reacting dimethylformamidine with an alkali metal salt of phenol in the presence of copper metal and / or copper salt in a solvent-free or organic solvent. The method for producing 4-fluoro-3-phenoxybromobenzene described in the above. 9. N- (3-chloro-4-fluorophenyl) -N ′, N′-dimethylformamidine is N, N
-After reacting dimethylformamide with phosgene,
This was reacted with 3-chloro-4-fluoroaniline,
The method for producing 4-fluoro-3-phenoxybromobenzene according to claim 8, which is obtained by treating with a hydroxide. 10. A reaction of 4-fluoro-3-phenoxyaniline with N, N-dimethylformamide and phosgene, followed by reaction with 3-chloro-4-fluoroaniline and treatment with hydroxide. N- (3-chloro-4
-Fluorophenyl) -N ', N'-dimethylformamidine and then the resulting N- (3-chloro-4-
(Fluorophenyl) -N ', N'-dimethylformamidine and an alkali metal salt of phenol are reacted in the presence of copper metal and / or copper salt in a solvent-free or organic solvent to form N
-(4-fluoro-3-phenoxyphenyl) -N ',
N′-dimethylformamidine was obtained and then the resulting N
-(4-fluoro-3-phenoxyphenyl) -N ',
The 4-fluoro-3-claim according to claim 1, which is obtained by adding hydrazine hydrate and alcohols to N'-dimethylformamidine and deprotecting the dimethylformamidine protecting group. A method for producing phenoxybromobenzene. 11. The method according to claim 7, wherein hydrazine hydrate, acetic acid and alcohols are used for deprotection of the dimethylformamidine protecting group.
A method for producing fluoro-3-phenoxyaniline. 12. The method according to claim 8, wherein the organic solvent used is diglyme or triglyme.
The process for producing 4-fluoro-3-phenoxybromobenzene according to any one of the above. 13. The method for producing 4-fluoro-3-phenoxybromobenzene according to claim 8, wherein the copper salt is chloride or bromide. 14. The method for producing 4-fluoro-3-phenoxybromobenzene according to claim 8, wherein the alkali metal salt of phenol is a sodium salt and / or a potassium salt. 15. The amount of phosgene is 1 to 2 mol per 1 mol of 3-chloro-4-fluoroaniline, and N, N
The method for producing 4-fluoro-3-phenoxybromobenzene according to claim 9 or 10, wherein the number of moles of -dimethylformamide used does not exceed. 16. The amount of N, N-dimethylformamide is from 1 to 1 mol per 3-chloro-4-fluoroaniline.
11. The method for producing 4-fluoro-3-phenoxybromobenzene according to claim 9, wherein the amount is 2 mol.