JPS59139377A - Fluorobenzene derivative and its preparation - Google Patents

Abstract

NEW MATERIAL:An ethylene ketal of 2-nitro-5-fluorophenyl alkyl ketone shown by the formula I (n is 1-5). USE:Useful as a raw material for an intermediate of agricultural chemicals. For example, an ethylene ketal shown by the formula I after deketalization is reacted with 3-chloro-4-hydroxybenzotrifluoride to give 3-(2'-chloro-4'-trifluoromethyl) phenoxyphenyl alkyl ketone, which is nitrated to synthesize 3-(2'-chloro-4'-trifluoromethyl)phenoxy-6-nitrophenyl alkyl ketone which is useful as an agricultural chemical by itself or an intermediate for agricultural chemicals. PROCESS:An ethylene ketal of 2-nitro-5-halogenophenyl alkyl ketone shown by the formula II (X is Br, or Cl) is reacted with potassium fluoride in an aprotic polar solvent, to give a compound shown by the formula I .

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to fluorobenzene derivatives useful as intermediate raw materials for agricultural chemicals and a method for producing the same. Ethylene ketal of phenylethyl ketone.

Ethylene ketal of 2-nitro-5-fluorophenyl-n-propyl ketone, ethylene ketal of 2-nitro-5-fluorophenyl-igo-7'rovir ketone,
Ethylene ketal of 2-nitro-5-fluorophenyl-n-butylketone, ethylene ketal of 2-nitro-5-fluorophenyl-5ee-fluorketone, 2-
The present invention relates to an ethylene ketal of nitro-5-7-orophenyl-tert-butyl ketone and an ethylene ketal of 2-nitro-5-fluorophenyl-n-pentyl ketone (hereinafter collectively abbreviated as compound A) and a method for producing the same.

Compound A is, for example, deketalized and then reacted with 3-chloro-4-hydroxypencitrifluoride to form 3-(2'
-Chloro-4'-trifluoromethyl)phenoxyphenylalkyl ketone, which is nitrated and useful as a pesticide itself or as an intermediate for pesticides.
'-Chloro-4'-trifluoromethyl)phenoxy-
6-Nitrophenyl alkyl ketones can be produced. Such compound A is a novel compound represented by the following general formula (1), which has not been previously known.

(In the formula, n is an integer of 1 to 5.) The method for producing compound A is to first introduce a nitro group into the meta position of a phenylalkyl ketone, then reduce the nitro group to an amino group, and then A conceivable method is to introduce a fluorine atom through diazotization thermal decomposition using the Mann reaction, followed by dinitration using a conventional method, and further converting to ethylene ketal according to a conventional method to obtain Compound A. However, this method requires long and complicated steps. Furthermore, the Ziemann reaction uses highly reactive noazonium salts, hydrofluoric acid, or hydrogen fluoride, which is dangerous and cannot be said to be an industrially advantageous method.

Therefore, the present inventor conducted various studies in order to produce Compound A using an industrially advantageous method. As a result, the inventors decided to use 2-nitro-5-halogen phenylalkyl ketone (halogen is chlorine or bromine) as a raw material, which can be produced at low cost. discovered a method to obtain Compound A by converting this into ethylene ketal and then replacing herodane with fluorine using potassium fluoride, and conducted extensive studies on the process of replacing halogen with fluorine using potassium fluoride, leading to the present invention. It is something that

According to the above method, the ethylene ketal of the raw material (7) 2-nitro-5-octophenylalkyl ketone represented by the following general formula (n) is obtained by metahalodanizing an inexpensive phenylalkyl ketone, and then using a conventional method. It can be obtained in high yield by nitration at the 5-position and ketalization in a conventional manner using ethylene glycol and an acid catalyst.

(wherein, Using potassium fluoride, the desired compound A can be obtained easily and in a high yield by replacing a fluorine atom with a fluorine atom. Attempts to directly fluorinate 2-nitro-5-octaronophenyl alkyl ketones (halodane hachlorine or bromine) with potassium fluoride resulted in extremely low yields, probably due to the decomposition of the ketone.

The solvent used in the fluorination of the present invention is preferably an aprotic organic solvent that does not alter the raw materials and products and does not alter itself, and the particularly preferred solvent is hashimethylsulfone. Sulfolane is also useful, but yields are lower than dimethylsulfone.

When herodan is chlorine and the solvent is dimethylsulfone,
The reaction temperature for obtaining high yields is 210°C to 300°C, preferably 230 to 280°C.

If the reaction temperature is less than 210°C, the conversion of the raw materials will not proceed and the yield will be low, whereas if it exceeds 300°C, the yield will decrease and the selectivity will deteriorate significantly. If the reaction time is short, the yield will be low, but if the reaction time is long, the yield will be low, so it is necessary to stop the reaction at an appropriate point.

The amount of potassium fluoride to be charged is suitably 1.0 to 5 times the mole of the compound represented by general formula (II). It is uneconomical even if the molar amount is increased by 5 times or more.

Regarding the concentration by form, the general formula (n
) is 2.5 to 100 parts by weight, preferably 5 to 70 parts by weight. Although it depends on the amount of potassium fluoride, in general, as the concentration increases, strong stirring is required, and even if stirring is sufficient, the conversion rate reaches a ceiling and tends to decrease. When using raw materials and solvents, the contamination of water will significantly reduce the yield.

The equipment should be thoroughly dried, moisture contamination during operation should be avoided as much as possible, and the reaction should be carried out in a closed container. If the solvent is dimethyl sulfo/, place the crystals in a desiccator containing phosphorus pentoxide in advance.
If sulfolane is used, phosphorus pentoxide is added and purified by distillation under reduced pressure before use. Further, potassium fluoride is used, which has been well ground in advance and stored in a desiccator containing phosphorus pentoxide. In addition, commercially available powdered KF (potassium fluoride manufactured by Morita Chemical Industry @)
Since it is in powder form, it is easy to manipulate. In some cases, after putting the starting materials, potassium fluoride, and a solvent into a reactor, add an appropriate amount of an aromatic organic solvent such as benzene, toluene, or xylene, and then azeotropically distilling off the water in the system by vacuum distillation. A method of raising the temperature to the reaction temperature can be adopted.

By this operation, the ethylene ketal of 2-nitro-5-herodanophenylalkyl ketone represented by the general formula (U) can be produced at a conversion rate of 40 to 80% and a selectivity of 50% or more. After the reaction, an organic solvent such as toluene that is insoluble in water and in which the raw material ketal and target compound A are soluble is added to water, the organic solvent phase is separated, and this organic solvent is distilled off. Compound A can be obtained separately.

The present invention will be explained in more detail below using Examples, Reference Examples, and Comparative Examples.

Below are margins Reference Example 1 51.0 g of m-chloroacetophenone in 11 flasks
(0.33 mol) and dropwise added 20 g of concentrated sulfuric acid while stirring vigorously at -10 to -15°C to become an orange transparent viscous liquid), followed by mixed acid 1 (70 g of nitric acid 46.69 + 313 g of concentrated sulfuric acid) ) was added dropwise over about 20 minutes while maintaining the temperature at -5 to -10°C. After the dropwise addition was completed, stirring was continued for an additional 5 minutes, and the mixture was poured onto crushed ice. After washing the generated solid with Okibetsu water,
After extraction with dichloromethane and washing with water, the dichloromethane layer was dried for several minutes, and dichloromethane was distilled off using an evaporator to obtain 65.5 g of crude 2-nitro-5-chloroacetophenone (
A pale yellow solid (purity 90%) was obtained.

This was purified by recrystallization with ethanol-n-hexane to obtain pale yellow needle crystals (purity: 98 or higher, melting point: 60°C).

Quantitative analysis was performed using high performance liquid chromatography (Cassam was Waters Microntapack C48, developing solution was methanol + water (75-I-25)).

Reference Example 2 2-nitro-5-chloroacetophenone synthesized in Reference Example-1 29.94. ! 7 (150 mmol), 10077 u of ethylene glycol, 100 d of )luene, and 1.00.9 (5.3 mmol) of p-)luenesulfonic acid hydrate, and the mixture was heated to reflux (approximately 110°C) while stirring. Ta. Subsequently, while distilling off little by little, toluene was added in an amount commensurate with the amount of distillation.

The amount of toluene added was 500% over a period of 4 hours while maintaining the temperature at approximately 110°C.
The reaction was terminated when M was reached. Add 200% of the contents to 5% of water.
After washing twice with water, the toluene layer was separated, and after dehydration with anhydrous sodium sulfate, the toluene was distilled off to form a pale yellow oil (semi-solid) 33.1
．． I got a 9. This is because the raw material 2-nitro-5 is an impurity.
- Ethylene ketal tear of crude 2-nitro-5-chlorophenylmethylketone incorporating 2.7 weight chloroacetophenone. Purity by recrystallization: 98. A pale yellow solid of El was obtained.

Example 1 50m/! A rotor is placed in the flask, and the ethylene ketal of 2-nitro-5-chlorophenylmethylketone (structural formula
CH2-CH2 1 (hereinafter abbreviated as compound B) 7.31.9 (30 mm! J mol) and 30 g of dimethylsulfone were added, and the atmosphere was replaced with nitrogen. This is followed by Kp2.6.9 (45 mmol)
was quickly put in, and after purging with nitrogen, it was sealed with a stopper and fixed so that it would not come off due to pressurization. This was immersed in an oil path and reacted at 240° C. for 5 hours with strong stirring.

After the reaction product was left to cool, it was opened, the solidified contents were dissolved with acetonitrile, the residue was collected door to door, and the acetonitrile was distilled off from the filtrate using an evaporator to obtain a solid. This is a mixture of the raw material Compound B and the ethylene ketal of ethylene of the product 2-nitro-5-fluorophenylmethylketone (hereinafter abbreviated as Compound C). The retention time for B was 7.1 minutes at 175°C, and the retention time for C was 4.5 minutes) and high performance liquid chromatography (hereinafter abbreviated as I (LC)).

The column used was Waters Micropinder Hack C18, and the developing solution was methanol + H20 (65 + 35
) o,5rnI! /min, retention time of B 10.1 min,
As a result of quantitative determination using a retention time of 7.5 minutes for C, the yield of compound C was 37 tI), the conversion rate of compound B was 63 qb (selectivity 5
9) obtained the following results. This solid was purified by preparative HLC, and Compound C with a purity of 97 mm or higher was separated as a colorless viscous oil, which was further recrystallized with n-hexane to obtain colorless needle crystals. Compound C has elemental analysis values of 52.1 parts carbon, 4.51 parts hydrogen, and 6.09 parts nitrogen (theoretical value: carbon 52.9 parts).
%, hydrogen 4.44% and nitrogen 6.17% = 1), and the melting point was 3.1°C. When I investigated the speckled rice bowl, I (-NMR spectrum showed that the benzene nucleus was split into many parts derived from the three hydrogen atoms.) Two peaks, δ = 3.9-4.2 and δ = 3.5-3.9, each of which is a multiplet derived from the four hydrogens bonded to the One peak 75 derived from hydrogen was observed at δ-1,8, and other peaks were barely visible.

Example 2 11.7 g (48 mmol) of Compound B, 20 g of dimethylsulfone, and 10.7 g (48 mmol) of Compound B. Og (] 70 mm IJ mol) at a reaction temperature of 250°C and a reaction time of 4 H.
The same operation as in Example flj1 was performed except that R was used for the reaction.

Elemental analysis values and succession of the obtained substance, Emperor is actually m191J1
It was in good agreement with the value of As a result of analysis by GLC and HLC, the yield of compound C was 32% and the conversion rate of compound B was 50% (selectivity 64%), which was ranked first.

Example 3 In a 100 flask, 14.6 g (60 mmol) of compound B, 60 g of dimethylsulfone, and 5.2 g of powdered KF
P (90811 mol) was charged, the reaction temperature was 232°C,
The same operation as in Example 1 was performed except that the reaction time was 8 HR.

The elemental analysis value and refractive index of the obtained substance were in good agreement with the values of Example 1. As a result of analysis by GLC and HLC, the yield of compound C was 32 mm, the conversion rate of compound B was 62 mm (selectivity 5
2) I obtained the following results.

Comparative Example 1 The same operation as in Example 1 was performed except that the core temperature and reaction time were changed, and the results shown in the following table were obtained.

The following margin Comparative Example 2 Compound B 11.7g (48 mmol), Sulfolane 24
．． 9 and powdered KF'8.7. Compound C
yield of 6.0%, conversion rate of compound B 17% (selectivity 35
h) I obtained the following results.

Comparative Example 3 5Qm, rotor in 6 flasks, 2-nitro-5-chlorophenylmethylketone 3.99. (20 mmol) and 24.9 sulfolane were added, and the atmosphere was replaced with nitrogen.

8.4 g (55 mmol) of well-pulverized cesium fluoride was placed in the flask, and after purging with nitrogen, the flask was sealed with a stopper. This at 35℃
After the reaction was stirred for 4 hours, the reaction solution was subjected to the same post-treatment as in Example 1. The conversion rate of 2-nitro-5-chlorophenylmethylketone was 63%, and the conversion of 2-nitro-5-fluorophenylmethylketone was 63%. A result with a yield of 0 was obtained.

Comparative example 4 5011L! , flask with rotor, 2-nitro-5-chlorophenylmethylketone 2.99. ! i'(15mi1
．． 1 mol) and sulfolane 6.7. ! 9 was added, and the atmosphere was replaced with nitrogen.

2.7 g (47 mmol) of Nogwood KF was quickly added to the flask, and after purging with nitrogen, the flask was sealed with a stopper. This was immersed in an oil path and reacted at 175°C under 3) strong IR stirring, and then the reaction solution was subjected to the same post-treatment as in Example 1.
The conversion of 2-nitro-5-chlorophenylmethylketone was 63%, and the yield of 2-nitro-5-fluorophenylmethylketone (D yield 0.7 = s) was obtained.

patent applicant Asahi Kasei Industries, Ltd. patent application agent Patent attorney Akira Aoki Patent Attorney Kazuyuki Nishitate Patent Attorney Ishi 1) Takashi Patent attorney Akira Yamaguchi

Claims (1)

[Claims] 1. Ethylene ketal O of 2-nitro-5-fluorophenylalkyl keto/represented by general formula (1) (wherein n is an integer from 1 to 5) 2. General formula (II) (wherein, X represents Br or Ct, and n is an integer of 1 to 5) The ethylene ketal of 2-nitro-5-phenylalkyl ketone is dissolved in an aprotic polar solvent The general formula (
1) A method for producing ethylene ketal of 2-nitro-5-fluorophenyl alkyl ketone. (wherein n is as defined above) 3. The method according to claim 2, wherein the halodane is chlorine. 4. The manufacturing method according to claim 2, wherein the halogen is chlorine, n is 1, and the reaction temperature is 210 to 300°C. 5. The amount of potassium fluoride charged is 1.0 to 5 times the mole of the compound represented by the general formula (U), and the charging needle of the compound represented by the general formula (II) is 2 to 100 parts by weight of the solvent.
．． The manufacturing method according to claim 2, wherein the amount is 5 to 100 parts by weight.