JPH0152A - Fluorobenzoic acid ester and its manufacturing method - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a novel fluorobenzoic acid ester and a method for producing the same.

(Prior art) In recent years, fluorine-containing pesticides and pharmaceuticals have attracted attention due to their excellent pharmacological and physiological activities, and are being actively researched. Plain quinoline antibacterial agents have been proposed. Among them, N-(3,5-dichloro-2,4-difluorophenyl)-N'-(2,6
-dichlorobenzoyl) urea is known to exhibit high activity as an insecticide. In addition, as the manufacturing method, 3.
A method of producing it by reacting 5-dichloro-2,4-difluorophenyl isocyanate and 2,6-cyfluorobenzamide is known.

(Problems to be Solved by the Invention) However, the fluorophenyl isocyanates used in the production method described in the above publication are generally produced by reacting the corresponding aniline with phosgene, but this phosgene is a poisonous gas. Since there are regulations regarding the use of phenyl isocyanate, a method for producing the phenyl isocyanate without using phosgene has been desired. Recently, as a method for producing isocyanate without using phosgene, 2,3,4,5-tetrachlorobenzoyl chloride is fluorinated to obtain 3,5-dichloro-2,4-difluorobenzoyl fluoride, and sodium azide is added to this. A method has been proposed for producing 3,5-dichloro-2,4-difluorophenyl isocyanate by reacting to produce the corresponding benzoyl azide and heating the same. (See International Patent Application Publication No. WO 36105487) However, this method was also not industrially satisfactory because it used explosive sodium azide.

(Means for Solving the Problems) In view of the current situation, the present inventors proposed a method for industrially producing fluorophenyl isocyanate using other methods (as a result of extensive research, they By reacting a chlorobenzoic acid ester and a metal fluoride in the presence of a specific catalyst and a specific solvent or in the absence of a solvent, side reactions of the ester group are suppressed and a new fluorobenzoic acid ester is produced. It was also discovered that the fluorophenyl isocyanate can be produced from this fluorobenzoic acid ester, and based on this knowledge, the present invention was completed.

That is, the present invention provides a general formula useful as an intermediate for producing a fluorine-containing urea insecticide or a fluorine-containing quinoline fungicide (wherein, X represents a fluorine atom or a hydrogen atom, and R represents an alkyl group). Fluorobenzoic acid ester represented by, and (in the formula,
Y represents a hydrogen atom or a chlorine atom, and R represents an alkyl group. ) A chlorobenzoic acid ester represented by In a polar solvent or as a catalyst, at least one salt selected from quaternary phosphonium salts, quaternary ammonium salts, and pyridinium salts, and at least one salt selected from crown ethers and polyalkylene glycols. A fluorobenzoic acid ester characterized by producing a fluorobenzoic acid ester represented by the general formula (wherein X and R have the same meanings as above) by reacting in the presence of a combination with a compound of The present invention provides a method for manufacturing.

The fluorobenzoic acid ester of the present invention has the above general formula (1
), in which X represents a hydrogen atom or a fluorine atom, and R represents a methyl group, ethyl group, propyl group, isopropyl group, t-butyl group, 5ec-butyl group, neopentyl group, etc. represents an alkyl group. Examples of such fluorobenzoic acid esters include 3.5-
Methyl dichloro-4-fluorobenzoate, ethyl 3.5-dichloro-4-fluorobenzoate, isopropyl 3.5-dichloro-4-fluorobenzoate, t-butyl 3.5-dichloro-4-fluorobenzoate , 5ec-butyl 3,5-dichloro-4-fluorobenzoate, 3.5
-Dichloro-4-fluorobenzoic acid-neopentyl, 3
．． Methyl 5-dichloro-2,4-difluorobenzoate,
Ethyl 3,5-dichloro-2,4-difluorobenzoate, isopropyl 3.5-dichloro-2,4-difluorobenzoate, t-butyl 3.5-dichloro-2,4-difluorobenzoate, 3. Examples include 5ec-butyl 5-dichloro-2°4-difluorobenzoate and neopentyl 3,5-dichloro-2,4-difluorobenzoate.

The chlorobenzoic acid ester used as a raw material in the method for producing a fluorobenzoic acid ester of the present invention is a compound represented by the general formula (II), in which Y
represents a hydrogen atom or a chlorine atom, R is a methyl group, an ethyl group, a propyl group, an isopropyl group, a t-butyl group, 5
Among the alkyl groups such as ec-butyl group and l-neopentyl group, neopentyl group is preferred. As such lolobenzoic acid ester, for example, 3,4.5-1
Methyl dichlorobenzoate, 3.4.5-ethyl dichlorobenzoate, 3.4.5-isopropyl trichlorobenzoate, 3,4.5-) tert-butyl dichlorobenzoate, 3,4.5- 5ec-butyl 1-dichlorobenzoate, 3.4.5-neopentyl trichlorobenzoate, 2
．． Methyl 3,4.5-tetrachlorobenzoate, 2.3,
4.5-Ethyl tetrachlorobenzoate, 2,3.4.5
-isopropyl tetrachlorobenzoate, 2.3.4.5
-t-butyl tetrachlorobenzoate, 2.3°4.5
-5ec-butyl tetrachlorobenzoate and 2.3
．． Examples include 4.5-tetrachlorobenzoic acid-neopentyl.

The quaternary phosphonium salts, quaternary ammonium salts and pyridinium salts used as catalysts in the production method of the present invention have the general formula % () (R1, R1, R3 and R4 are each an alkyl group, an aryl group or an aralkyl group, which may be the same or different from each other,
゛ is a halogen atom. Also, R', R- and R''
are each an alkyl group, and they may be the same or different from each other, and X'' is a halogen atom. Specific examples include quaternary phosphonium salts such as tetraphenylphosphonium bromide, tetraphenylphosphonium chloride, benzyltributylphosphonium chloride, benzyltriphenylphosphonium chloride, triphenylmethylphosphonium chloride, tetramethylammonium chloride, tetraethylammonium bromide, Tetrabutylammonium bromide.

Tetraptylammonium iodide, tetrahexylammonium bromide, tetraoctylammonium chloride, ethyltrimethylammonium chloride, butyltriethylammonium chloride, lauryltrimethylammonium bromide.

Ethyltributylammonium bromide, isobutyltributylammonium bromide, hexyltributylammonium bromide, octyltributylammonium bromide, lauryltributylammonium bromide,
Methyltrioctylammonium bromide, tetraphenylammonium chloride, benzyltrimethylammonium bromide, benzyltriethylammonium chloride, benzyltripropylammonium chloride.

Quaternary ammonium salts such as benzyltrihexylammonium chloride and benzyltrioctylammonium chloride, N-(2-ethylhexyl)-4-dimethylaminopyridinium chloride.

N-(2-ethylhexyl)-4-di-n-butylaminopyridinium chloride, N-(2-ethylhexyl)
-4-di-n-hexylaminopyridinium chloride,
N-neopentyl-4-dimethylaminopyridinium chloride, N-neopentyl-4-di-n-butylaminopyridinium chloride, N-neopentyl-4-di-n
-hexylaminopyridinium chloride, N-(2-ethylhexyl)-4-dimethylaminopyri, dinium chloride, N-(2-ethylhexyl)-4-di-n-butylaminopyridinium bromide, N-(2- ethylhexyl)-4-di-n-hexylaminopyridinium bromide, N-neopentyl-4-di-methylaminopyridinium bromide.

Examples include pyridinium salts such as N-neopentyl-4,-di-n-butylaminopyridinium bromide and N-neopentyl-4-di-n-hexylaminopyridinium bromide.

Furthermore, in the present invention, at least one salt selected from the above-mentioned quaternary phosphonium salts, quaternary ammonium salts and pyridinium salts and at least one salt selected from crown ethers and polyalkylene glycols are used as catalysts. Combinations with species compounds can also be used.

As the crown ether, for example, 18-crown-
6, dibenzo-18-crown-6, dicyclohexanone 1B-crown-6,12-crown-4,15-crown-5, and dibenzo-24-crown-8, among others, 18-crown- 6, dibenzo-18-crown-6, and dicyclohexano-18-crown-6 are preferred.

In addition, as polyalkylene glycols, the general formula % () (in the formula, R1 is an alkylene group, R9 and R'' are each a hydrogen atom, an alkyl group, an aryl group, or an aralkyl group, and they are the same) or may be different from each other, and Z is an integer of 2 or more.) Examples of such compounds include diethylene glycol, triethylene glycol, and tetraethylene. Glycol, pentaethylene glycol, hexaethylene glycol, diisopropylene glycol.

dipropylene glycol, tripropylene glycol,
Glycols such as tetrapropylene glycol and tetramethylene glycol, and monomethyl and monoethyl of these glycols.

Monoalkyl ethers such as monopro and monobutyl ether, dialkyl ethers such as tetraethylene glycol dimethyl ether and pentaethylene glycol dimethyl ether, phenyl ethers, benzyl ethers, as well as polyethylene glycol dimethyl ether (average molecular weight 1300), polyethylene glycol dibutyl ether (average molecular weight: 300), polyethylene glycol dimethyl ether (average molecular weight: 400), etc. Among them, compounds in which R9 and R1 (l are both alkyl, aryl, or aralkyl groups) are preferred.

In the present invention, the above-mentioned crown ethers and polyalkylene glycols may be used alone or in combination of two or more, and crown ethers and polyalkylene glycols may be used in combination.

In the present invention, the amount of catalyst used is determined by the general formula (If
) is usually selected in an amount of 1 to 50 mol %, preferably 5 to 40 mol %, based on 1 mol of the chlorobenzoic acid ester. In addition, when a crown ether or polyalkylene glycol is used in combination with the above-mentioned quaternary phosphonium salt, quaternary ammonium salt, or pyridinium salt as a catalyst, the amount of crown ether or polyalkylene glycol is It is desirable to use the compound in a molar ratio not exceeding four times that of the quaternary phosphonium salt, quaternary ammonium salt and pyridinium salt. When a crown ether or polyalkylene glycol is used alone without using a quaternary phosphonium salt, the desired fluorobenzoic acid ester is hardly produced.

Examples of the metal fluoride used in the method of the present invention include potassium fluoride and cesium fluoride, and spray-dried potassium fluoride is particularly preferred. These metal fluorides are preferably used in a ratio of 1 to 2 equivalents to the replaceable chlorine atom of the chlorobenzoic acid ester represented by the general formula (U),
Further, this reaction can usually be carried out in the presence of a solvent or without a solvent for the purpose of smoothly proceeding the reaction.

When using a solvent, it is preferable to use an aprotic polar solvent such as sulfolane, dimethylsulfone, 1,3-dimethylimidacylin-2-one, dimethylformamide, N-methylpyrrolidone, tetramethylurea, dimethylsulfoxide, etc. .

Furthermore, the quaternary phosphonium salt as a catalyst.

When at least one selected from quaternary ammonium salts and pyridinium salts is used alone, the reaction is preferably carried out in an aprotic polar solvent. Further, the amount of this aprotic polar solvent to be used is determined according to the above general formula (II).
[Usually 100 to 1000 g, preferably 150 to 500 g per mol of halogenated benzaldehyde represented by
selected within the range of g.

In addition, this reaction is usually carried out at 150 to 300°C, preferably at 16°C.
The temperature is selected within the range of 0 to 240°C. There is no particular restriction on the reaction pressure, and the reaction may be carried out at normal pressure or under increased pressure. When reacting under pressure, 10 kg/
Although a pressure of 1.5 cm or less is preferable, industrially it is preferable to carry out the reaction at normal pressure.

Further, a reaction time of about 1 to 20 hours is sufficient.

The novel fluorobenzoic acid ester obtained by the method of the present invention is obtained by reacting with hydrazine according to a conventional method to obtain the corresponding fluorobenzoyl hydrazide, and further reacting with sodium nitrite to obtain the corresponding fluorobenzoyl azide. The above-mentioned fluorophenyl isocyanate can be produced by obtaining and heating this. Furthermore, by reacting this fluorophenyl isocyanate with benzamide, the fluoride-containing urea fungicide described in JP-A-57-126460 can be produced.

(Effects of the Invention) According to the method of the present invention, a chlorobenzoic acid ester represented by general formula (II) and a metal fluoride are combined with a specific catalyst,
By reacting in the presence of a specific solvent, − in the formula
Fluorobenzoic acid esters can be produced industrially by suppressing side reactions such as transfer of OH groups to nuclei, decarboxylation, and generation of high-boiling substances. Further, the fluorobenzoic acid ester obtained by this method is a compound useful as an intermediate for producing fluorophenyl isocyanate.

Example Next, the present invention will be explained in more detail with reference to Examples.

Example 1 In a 50-1 four-loaf flask equipped with a water separator and a stirrer,
Spray-dried potassium fluoride (manufactured by Morita Chemical Industries, Ltd.) 6
．． 0 g (104 gm+ol), tetraphenylphosphonium bromide l', 7 g (4 gmol)
, 12 g of anhydrous sulfolane, and 20-1 toluene were added, and toluene was distilled off while stirring while heating on an oil bath to perform azeotropic dehydration. After heating the liquid temperature to 140°C, the pressure was reduced to 45ssHg, and almost all of the remaining toluene was distilled off. The interior of the reaction vessel was cooled to 100°C, replaced with nitrogen gas, and 2.3,4.5-tetra 13.1 g (40 gaol) of neopentyl chlorobenzoate was added, and the mixture was stirred at 190° C. under a nitrogen gas atmosphere to conduct a reaction for 15 hours.

After the reaction is completed, the reaction mixture is cooled and heated with toluene for 100s+
After adding 1 and filtrating the inorganic matter, dilute the filtrate with 200ml of water.
Washed twice. The toluene layer was taken out and dried over anhydrous sodium sulfate, and the toluene was distilled off using a rotary evaporator to obtain 11.0 g of a brown oily substance. The obtained oily substance was distilled under reduced pressure to obtain 3,5-dichloro-2 as a colorless oily substance.
, 7.2 g of neopentyl 4-difluorobenzoate was obtained. The yield was 61%. Infrared absorption spectrum analysis (hereinafter abbreviated as IR) and nuclear magnetic resonance spectrum analysis (hereinafter abbreviated as NMR) of this compound will be described below.

The analysis results of mass spectrum analysis (hereinafter abbreviated as Mass) are shown.

Boiling point: 115-b Melting point: 38-42°C I R'(KBr); 1720 (C=O), 1250
(C-F) cm-'Mass s+/e: 29
6(M”), 209(M”-CHxC(CHs)s
) Example 2 Neopentyl 3,4.5-)dichlorobenzoate in place of neopentyl 2,3.4.5-tetrachlorobenzoate in Example 1 8.9 g (30 steel-ol), spray-dried potassium fluoride 2.6 g (45 vwol) of tetraphenylphosphonium bromide 1. 3g (31m
6 in the same manner using 9 g of anhydrous sulfolane.
A time reaction was performed. After post-treatment in the same manner, 5.3 g of neopentyl 3,5-dichloro-4-fluorobenzoate was obtained by distillation under reduced pressure. Furthermore, the distillation residue was subjected to column chromatography using silica gel and eluted with benzene to obtain pale yellow plate-like crystals of 3,5-dichloro-4.
-2.0 g of neopentyl fluorobenzoate was obtained. The yield was 87%. The physical properties are shown below.

Boiling point: 137-140°C/7 mm/g Melting point;
96-98℃ IR (KBr); 1730 (C=O), 1240 (
C-F) cm-'Mass m/e: 27B(
? I”), 191 (M”-CHzC(CII+)
*) Example 3 In Example 1, 2. 3. 4. Neopentyl 5-tetrachlorobenzoate 9.9 g (30+gnol
).

Spray dried potassium fluoride4. 0 g (69o+
mol) Using 9 g of sulfolane, 0.8 of N-.(2-ethylhexyl)-4-dimethylaminopyridinium chloride was added in place of tetraphenylphosphonium bromide.
The reaction and post-treatment were carried out in the same manner as in Example 1 except that g (3-sol) was used to obtain 5.7 g of neopentyl 3,5-dichloro-2,4-difluorobenzoate. Yield is 64
%Met.

Example 4 The same procedure as in Example 2 was carried out except that 0.8 g (3v++ol) of N-(2-ethylhexyl)-4-dimethylaminopyridinium chloride was used instead of tetraphenylphosphonium bromide in Example 2. 3.5 -dichloro-4-
7.6 g of neopentyl fluorobenzoate was obtained. The yield was 91%.

Example 5 In a 50 ml flask equipped with a condenser and a stirrer, 1.9 g (33 mmol) of spray-dried potassium fluoride (manufactured by Laporte Chew) and 1.9 g (33 mmol) of tetraphenylphosphonium bromide were added. 1 g (2.5 mmol
), 18-crown-6 to 0. 7g (2,5
vwol), 3. 6.4 g (25 n+mol) of ethyl 4.5-trichlorobenzoate was added, heated on an oil bath, and reacted at 210° C. for 2 hours under a nitrogen atmosphere.

The reaction vessel was cooled, diluted with toluene 40a+1, inorganic salts were filtered, and toluene was distilled off. The residue was distilled under reduced pressure to obtain 3.4 g of ethyl 3.5-dichloro-4-fluorobenzoate. The yield was 57%. The physical properties are shown below.

Claims (1)

[Claims] 1) Fluorobenzoic acid ester represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, X represents a fluorine atom or a hydrogen atom, and R represents an alkyl group.) . 2) A chlorobenzoic acid ester and a metal fluoride represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, Y represents a hydrogen atom or a chlorine atom, and R represents an alkyl group.) The reaction is carried out in an aprotic polar solvent in the presence of at least one salt selected from quaternary phosphonium salts, quaternary ammonium salts, and pyridinium salts as a catalyst, and the general formula ▲ mathematical formula, chemical formula, table, etc. ▼ (In the formula, X represents a fluorine atom or a hydrogen atom, and R represents an alkyl group.) A method for manufacturing a fluorobenzoic acid ester, which is characterized by manufacturing a fluorobenzoic acid ester represented by the following formula. 3) A chlorobenzoic acid ester and a metal fluoride represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, Y represents a hydrogen atom or a chlorine atom, and R represents an alkyl group.) Presence of a combination of at least one salt selected from quaternary phosphonium salts, quaternary ammonium salts, and pyridinium salts as a catalyst and at least one compound selected from crown ethers and polyalkylene glycols. The following reaction is performed to produce a fluorobenzoic acid ester represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, X represents a fluorine atom or a hydrogen atom, and R represents an alkyl group.) A method for producing a fluorobenzoic acid ester, characterized by: