JPH10182568A - 4-fluoro-3-phenoxyaniline and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce an inexpensive raw material intermediate without any problems in environment such as production of eutrophic wastewater in the production of a bromide effectively usable as a raw material for insecticides. SOLUTION: N,N-Dimethylformamide is reacted with phosgene and the resultant compound is then reacted with 3-chloro-4-fluoroaniline and the resultant compound is then treated with a hydroxide to provide N-(3-chloro-4- fluorophenyl)-N',N'-dimethylformamidine, which is subsequently reacted with an alkali metallic salt of phenol in the presence of metallic copper and/or a copper salt in or without an organic solvent to afford N-(4-fluoro-3- phenoxyphenyl)-N',N'-dimethylformamidine. Hydrazine hydrate and alocohols are then added to the resultant N-(4-fluoro-3-phenoxyphenyl)N',N'- dimethylformamidine to deprotect the protecting group of the dimethylformamidine. Thereby, 4-fluoro-3-phenoxyaniline is obtained.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to 4-fluoro-3-
The present invention relates to phenoxyaniline and a method for producing the same. The 4-fluoro-3-phenoxyaniline obtained according to 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
No. 5928).

[0005]

2. Description of the Related Art 4-Fluoro-3-phenoxyaniline is a novel compound. JP-A-62-5928 discloses a compound represented by the general formula 2 as one of the starting materials of the general 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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[0009] Alternatively, malonic acid is used as shown in the following chemical formula (4) to increase the amount of carbon (British Patent No. 2187452 A1).
(See Production Example 2) Synthesized by any method.

[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.

[0012]

However, in the above methods, all 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, from the phosphorus compound used in the reaction for replacing the alcoholic hydroxyl group with a bromine atom. Furthermore, both use relatively expensive lithium aluminum hydride to reduce esters to alcohols, and are not necessarily industrially preferable from the viewpoint of economic efficiency and protection of the natural environment. Was.

In view of these 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, a novel compound N- (3-chloro-4-fluorophenyl) -N ′, N′-dimethylformamidine is obtained, which is reacted with an alkali metal salt of phenol. Thus, a novel compound N- (4-fluoro-3-phenoxyphenyl) -N ′, N′-dimethylformamidine was obtained, and hydrazine hydrate, alcohols, and more preferably acetic acid were added thereto. A dimethylformamidine protecting group is easily deprotected from the N- (4-fluoro-3-phenoxyphenyl) -N ′, N′-dimethylformamidine in good yield, and a new product is obtained. Compounds in which 4-fluoro-3-phenoxyphenyl aniline, by using it as an intermediate, without the environment such as the occurrence of eutrophication drainage problems, and industrially without problems at the production the reduction 2
It was found that a bromide represented by the formula (1) was obtained, and the present invention was completed.

[0014]

That is, the present invention is to provide a novel compound, 4-fluoro-3-phenoxyaniline.

Further, the present invention provides a method of reacting N, N-dimethylformamide with phosgene, followed by reacting with 3-chloro-4-fluoroaniline, treating with a hydroxide to give N- (3-chloroform). -4-fluorophenyl) -N ',
N′-dimethylformamidine was obtained and then the resulting N- (3-chloro-4-fluorophenyl) -N ′,
N- (4-fluoro-3-phenoxyphenyl) -N 'is obtained by reacting N'-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'-dimethylformamidine, and then hydrazine hydrate and alcohols were added to the obtained N- (4-fluoro-3-phenoxyphenyl) -N ', N'-dimethylformamidine to give dimethylformamidine. Deprotecting a protecting group; 4
The present invention provides a method for producing -fluoro-3-phenoxyaniline.

[0016]

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

4-Fluoro-3-phenoxyaniline is a novel compound, which is obtained by reacting N, N-dimethylformamide with phosgene, followed by reacting with 3-chloro-4-fluoroaniline, and using hydroxide. Process to N- (3
-Chloro-4-fluorophenyl) -N ', N'-dimethylformamidine and then the resulting N- (3-
Chloro-4-fluorophenyl) -N ', N'-dimethylformamidine is reacted with an alkali metal salt of phenol 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, and then hydrazine water was added to the obtained N- (4-fluoro-3-phenoxyphenyl) -N', N'-dimethylformamidine. It can be obtained by adding a hydrate and an alcohol and deprotecting the dimethylformamidine protecting group.

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-trichloroethane, 1,1,2-trichloroethylene, 1,1,2,2
Halogenated hydrocarbons such as tetrachloroethylene, chlorobenzene, o-dichlorobenzene, and chlorofluorocarbon; ethers such as diethyl ether, diisopropyl ether, diphenyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether; and N, N-dimethylformamide. No. It is also possible to mix these solvents.

[0019] 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 the practice of the present invention, the amount of N, N-dimethylformamide used is about 1 to about 2 mol, preferably about 1 to about 1.5 mol, per 1 mol of 3-chloro-4-fluoroaniline. Range. Even if you use more than this,
There is no corresponding improvement in yield.

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 moles, preferably about 2.5 to about 3.5 moles per mole 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 usually carried out 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.

In the present invention, N- (3-chloro-4-fluorophenyl) -N ',
N'-dimethylformamidine is then reacted with an alkali metal salt of phenol in the presence of copper metal or copper salt in a solvent-free or organic solvent to give N- (4-fluoro-3-phenoxyphenyl), the desired product. -N ', N'-dimethylformamidine is obtained.

Examples of the alkali metal of phenol include sodium salts and potassium salts, and more specifically, sodium phenoxide and potassium phenoxide. 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.

[0032] 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 is obtained by performing a usual operation such as adding water, removing metallic copper or 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 practice of the present invention, the deprotection of the dimethylformamidine protecting group is carried out with hydrazine hydrate and, if necessary, with addition of acetic acid. Methanol as a solvent,
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 without using acetic acid, 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.

[0038] 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.

After completion of the reaction, the target compound, 4-fluoro-3-phenoxyaniline, can be obtained by performing a usual operation such as extraction with an organic solvent and concentration. The 4-fluoro-3-phenoxyaniline can be used as it is or, if necessary, further purified by means such as distillation and column chromatography, and used as a raw material for insecticides.

[0041]

According to the present invention, 4-
Fluoro-3-phenoxyaniline is a relatively inexpensive 3
-Chloro-4-fluoroaniline is a novel substance which can be used as a main raw material, which is useful as a raw material for the insecticide shown in the above-mentioned chemical formula 1 by using a production method shown in Reference Examples described later. Using bromide represented by 2 as a raw material, expensive lithium aluminum hydride or 4
-Can be produced at relatively low cost without using -fluoro-3-phenoxybenzaldehyde and without using a phosphorus compound which causes a problem of eutrophic wastewater;
Its industrial utility value is extremely large.

[0042]

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 N, N-dimethylformamide 60.26 g (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. The melting point 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), phenol potassium salt 1.98 g (0.0150 mol) and phenol sodium salt 1.74 g (0.0150 mol) )
Was added with 40 g of toluene and 27.0 g of diethylene glycol dimethyl ether, and the water content of the reaction solution was 1000 ppm.
It was azeotropically dehydrated until it became the following. Then, 0.08 g (0.0006 mol) of cupric chloride was added to the reaction product after the azeotropic dehydration, toluene was distilled off under normal pressure, and the reaction was carried out at 155 ° C. for 24 hours. 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-fluoro Aniline = 66.2:
A reaction product of 2.9: 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, the magnesium sulfate was filtered, toluene was distilled off under reduced pressure, and the residue was dried under vacuum to obtain a black oily substance [3.36 g (GC purity 66.2%, yield 5).
7.6%)]. The obtained black oil was purified by silica gel column chromatography to obtain a light brown oily substance [N-
(4-fluoro-3-phenoxyphenyl) -N ′,
N'-dimethylformamidine]. ¹ H NMR
(90 MHz, δ, CDCl ₃ ) 7.43 to 6.59
(M, 9H), 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 (δ, CDCl ₃ ) 7.42 was obtained.
-6.63 (m, 6H), 6.46-6.30 (m, 2
H), 3.37 to 3.17 (br, 2H). Distilled and purified, b. p. 143 to 146 ° C / 0.2m
mHg.

Examples 2 to 6 In Example 1, the deprotection reaction of dimethylformamidine was carried out by using methanol instead of 2-propanol, changing the amount of hydrazine monohydrate, and adding acetic acid. Table 1 shows the results.

[0047]

[Table 1] The amounts of hydrazine hydrate and acetic acid in the table represent the molar ratio to N- (4-fluoro-3-phenoxyphenyl) -N ', N'-dimethylformamidine.

Reference Example 1 (Production example of bromide shown in Chemical formula 2) 2.40 g (9.995 mmol) of the oily substance [4-fluoro-3-phenoxyaniline] obtained in Example 1 was added to N, N-dimethyl. Formamide 21.7 g, acetic acid 2.4
6 g, and 4.91 g of an aqueous solution of sodium nitrite [0.69 g of sodium nitrite (1
0.1 mmol)] and kept warm for 30 minutes. This reaction solution was prepared in a separate container, and prepared as cuprous bromide 1.98.
g (13.8 mmol) and a 47% aqueous solution of hydrobromic acid.
87 ° C. (16.7 mmol) to a solution of 20 ° C.-3
The mixture was added dropwise at 0 ° C. over 1 hour and kept warm for 3 hours. Water 10
g and 20 g of toluene, the insolubles were filtered, the organic layer was separated, the aqueous layer was extracted with toluene, and the organic layers were combined. The combined organic layers were sequentially washed with a 6% aqueous sodium hydrogen carbonate solution and water, dried over magnesium sulfate, magnesium sulfate was filtered, the solvent was distilled off under reduced pressure, and the residue was dried under vacuum to obtain a black oily substance 4 0.75 g (GC purity 49.8%, yield 88.6%) was obtained. This black oil was purified by distillation to obtain a pale yellow oil [4-fluoro-3-phenoxybromobenzene]. B. p. Was 147 to 149 ° C / 4 mmHg.

Then, 3.79 g (0.156 mol) of magnesium and 80 g of dry tetrahydrofuran were added to the reactor purged with nitrogen, and the pale yellow oily substance [4-fluoro- 3-phenoxybromobenzene] 40.00 g (purity 94.7%, 0.14
2 mol) and 200 g of dry tetrahydrofuran were added dropwise and stirred at room temperature overnight. Allyl bromide 2
2.31 g (0.184 mol) was added dropwise at 60 ° C., and the mixture was kept warm for 4 hours. After keeping the temperature warm, 250 g of a 10% aqueous ammonium chloride solution was added, and 140 g of dichloromethane was added.
Extracted times. The organic layer was washed with 280 g of water, dried over magnesium sulfate, filtered over magnesium sulfate, evaporated under reduced pressure to remove the solvent, and dried under vacuum to obtain a pale yellow oil. The yield was 41.19 g, the GC purity was 59.4%, and the yield was 75.6%. Further, the pale yellow oil was purified by distillation to obtain a colorless oil [1-fluoro-2-phenoxy-4- (2-propenyl) benzene]. B. p. Is 152-155 ° C / 5mmH
g.

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). N
MR data (CDCl ₃ ) 2.14 (tt, 2H),
2.71 (t, 2H), 3.36 (t, 2H), 6.8
-7.5 (m, 8H)

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Noriotada Matsuo 4-2-1 Takashi Takarazuka-shi, Hyogo Sumitomo Chemical Industries, Ltd.

Claims (8)

[Claims] 1. A 4-fluoro-3-phenoxyaniline. 2. A reaction between N, N-dimethylformamide and phosgene, followed by reaction with 3-chloro-4-fluoroaniline, treatment with a hydroxide, and N- (3-chloro-4- (Fluorophenyl) -N ′, N′-dimethylformamidine, and then the obtained N- (3-chloro-4-fluorophenyl) -N ′, N′-dimethylformamidine and an alkali metal salt of phenol Is reacted in the presence of copper metal and / or copper salt in a solvent-free or organic solvent to give N- (4-fluoro-3-phenoxyphenyl)
-N ', N'-dimethylformamidine was obtained and the resulting N- (4-fluoro-3-phenoxyphenyl)
Hydrazine hydrate and alcohols are added to -N ', N'-dimethylformamidine to deprotect the dimethylformamidine protecting group.
A method for producing 3-phenoxyaniline. 3. The amount of N, N-dimethylformamide is 3
1 to 2 relative to 1 mole of -chloro-4-fluoroaniline
The method for producing 4-fluoro-3-phenoxyaniline according to claim 2, wherein the amount is mole. 4. The amount of phosgene is 1 to 2 mol per 1 mol of 3-chloro-4-fluoroaniline, and N, N-
3. The method for producing 4-fluoro-3-phenoxyaniline according to claim 2, wherein the number of moles of dimethylformamide used does not exceed the number of moles. 5. The method for producing 4-fluoro-3-phenoxyaniline according to claim 2, wherein the alkali metal salt of phenol is a sodium salt and / or a potassium salt. 6. The method for producing 4-fluoro-3-phenoxyaniline according to claim 2, wherein the copper salt is chloride or bromide. 7. The method for producing 4-fluoro-3-phenoxyaniline according to claim 2, wherein the organic solvent used is diglyme or triglyme. 8. Deprotection of a dimethylformamidine protecting group from N- (4-fluoro-3-phenoxyphenyl) -N ′, N′-dimethylformamidine using hydrazine hydrate, acetic acid and alcohols. The method for producing 4-fluoro-3-phenoxyaniline according to claim 2, wherein