JPH0556339B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula [In the formula, X represents a chlorine atom or a bromine atom. ] The present invention relates to 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonyl chloride (hereinafter referred to as the compound of the present invention) represented by the following and a method for producing the same. reducing the compound of the present invention and reacting it with haloacetic acid;
General formula that can be produced by deacetylation, reaction with 3,4,5,6-tetrahydrophthalic anhydride, and then esterification [In the formula, R is a _C1 - _C6 alkyl group, a _C3 - _C7 cycloalkyl group, a _C3 - _C6 alkenyl group, a _C3 - _C6 alkynyl group, a _C2 - _C6 haloalkyl group, a C1- _C6 It represents a _C4 alkoxy ( _C1 - _C4 ) alkyl group, a _C1 - _C6 alkoxycarbonyl ( _C1 - _C3 ) alkyl group, or a phenyl group, and X has the same meaning as above. ] 2-substituted phenyl-4,5,6,7-
Tetrahydro-2H-isoindole-1,3-
Zion does not cause harmful chemical damage to major crops such as corn, soybeans, wheat, cotton, and rice, and exhibits sufficient herbicidal efficacy against many weeds (Japanese Patent Application Laid-Open No. 59-212472). . The compounds of the present invention are important as intermediates thereof. Compounds of the invention typically have the general formula [In the formula, X represents the same meaning as above. ] An alkali metal salt such as sodium or potassium or an organic base salt such as pyridine of 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonic acid represented by It can be produced by reacting a chlorinating agent such as phosphorus pentachloride or phosphorus oxychloride in a solvent or in the absence of a solvent at 0°C to 200°C for 0.5 to 5 hours and chlorinating it. Examples of the solvent include halogenated hydrocarbons such as chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, and dichlorobenzene, or mixtures thereof. After completion of the reaction, the reaction solution is subjected to normal post-treatments such as extraction with an organic solvent and concentration, or further purified by chromatography, recrystallization, etc. as necessary to obtain the desired general formula. []
The compound of the present invention represented by can be obtained. 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonic acid represented by the general formula [], which is a raw material compound in the above method, can be efficiently produced by the following method. That is, the general formula [In the formula, X represents the same meaning as above. ] 2-fluoro-4-haloacetanilide and an equivalent to an excess amount of oleum relative to the 2-fluoro-4-haloacetanilide are heated at 0°C to 0°C without a solvent or in concentrated sulfuric acid as a solvent.
It can be produced by reacting at 100°C for 0.5 to 5 hours and sulfonating. After the reaction is complete, the reaction solution is added dropwise to ice or ice water, the precipitated crystals are collected, and the usual post-sulfonation treatment is performed, such as washing with cold water, etc., or if necessary, operations such as recrystallization are performed. The desired 5-(N-acetylamino)-4-
Fluoro-2-halobenzenesulfonic acid [ ] is obtained. In addition, the obtained 5-(N-acetylamino)-4
-Fluoro-2-halobenzenesulfonic acid []
To obtain the corresponding sulfonate, add an aqueous solution of sodium hydroxide, potassium hydroxide, sulfonic acid, etc., or a base such as pyridine, further concentrate under reduced pressure, and then wash the residue with cold water and filter it. be able to. In addition, 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonic acid [] obtained by sulfonating 2-fluoro-4-haloacetanilide [] can be chlorinated without isolating it. The following methods can be used to efficiently obtain compounds. That is, 2-fluoro-4-haloacetanilide [] is reacted with 1 to 20 equivalents of 20% or more fuming sulfuric acid in the absence of a solvent or in concentrated sulfuric acid as a solvent at 0°C to 20°C to sulfonate it. Then, the obtained sulfonic acid is not isolated, but is reacted with 1.0 to 10 equivalents of a chlorinating agent such as carbon tetrachloride, chloroform, or sulfur dichloride at 60°C to 65°C for 1 to 96 hours to undergo chlorination. It can be manufactured by After the completion of the reaction, the reaction solution is poured into ice water and subjected to usual post-treatments such as organic solvent extraction and concentration, or if necessary, purified by operations such as recrystallization to obtain the desired compound of the present invention. can get. In addition, 2-fluoro-4-haloacetanilide of the general formula [], which is a raw material compound, is
It can be produced by the production method described in Japanese Patent No. 51521. The present invention will be explained in more detail below using manufacturing examples. Production example 1 5-(N-acetylamino)-2-bromo-4-
175.8g of fluorobenzenesulfonic acid and pyridine
130 g was added and stirred for 1 hour, and the precipitated crystals were collected and washed with diethyl ether. 199.5 g of the pyridine salt of the sulfonic acid thus obtained
was suspended in 560 ml of chloroform, and 140.7 g of phosphorus pentachloride was added.
After adding, the mixture was stirred at 60°C to 70°C for 1 hour. The reaction solution was allowed to cool, water was added, and extracted with chloroform.
The extract was dried and concentrated to obtain 73.25 g of 5-(N-acetylamino)-2-bromo-4-fluorobenzenesulfonyl chloride. mp155℃～156℃ Using the same method, 5-(N-acetylamino)-
From 2-chloro-4-fluorobenzenesulfonic acid, 5-(N-acetylamino)-2-chloro-4
-Fluorobenzenesulfonyl chloride was obtained. mp138℃～139℃ Production Example 2 173.2g of N-(4-bromo-2-fluorophenyl)acetamide was suspended in 80ml of concentrated sulfuric acid and heated at 10℃.
After dropping 340ml of 60% oleum at ~20℃,
Stir for hours. After that, the reaction solution was added dropwise to 500 g of ice water at 10°C to 20°C, the precipitated crystals were removed, and the mixture was cooled with cold water.
Washed with 400ml. The crystals are dried under reduced pressure and heat,
175.8 g of 5-(N-acetylamino)-2-bromo-4-fluorobenzenesulfonic acid was obtained. mp300℃ or higher NMR (D ₆ -DMSO) δppm2.0 (3H, s), 7.45 (1H, d) 8.3 (1H, d), 9.7 (1H, m) In the same manner, N-(4-chloro 5-(N-acetylamino)-2-chloro-4-fluorobenzenesulfonic acid was obtained from -2-fluorophenyl)acetamide. mp300℃ or higher NMR (D ₆ -DMSO) δppm2.0 (3H, s), 7.2 (1H, d), 8.2 (1H, d), 9.6 (1H, m) Production example 3 4-chloro-2-fluoroacetanilide 100
g was added to 80 ml of concentrated sulfuric acid under ice cooling. 200 ml of 60% oleum was added dropwise to this at 0-10°C, and the mixture was stirred for 1 hour.
300 ml of carbon tetrachloride was added at room temperature and stirred at 60-65°C for 5 hours. After cooling to room temperature, add 300 ml of carbon tetrachloride.
ml and stirred at 60-65°C for 5 hours. After cooling, the reaction solution was poured into ice water and extracted with ethyl acetate. The extract was washed with water, dried, and concentrated to obtain 189 g of 4-chloro-2-fluoro-5-chlorosulfonylacetanilide. mp138-139℃ In the same manner, 4-bromo-2-fluoro-
5-chlorosulfonylacetanilide was obtained. mp155-156℃ In addition, from the compound of the present invention, by the following method,
2-substituted phenyl-4,5, with herbicidal activity
6,7-tetrahydro-2H-isoindole-
1,3-dione [ ] can be obtained. That is, the compound of the present invention has a 3.0
~20 equivalents of reducing agents such as zinc, stannous chloride, iron, etc.
By using 3.0 to a large excess of acid such as acetic acid, hydrochloric acid, sulfuric acid, etc., and reacting at 50°C to 100°C for 0.1 to 24 hours to reduce the general formula [In the formula, X represents the same meaning as above. ] 5-(N-acetylamino)-4-fluoro-2-halobenzenethiol can be obtained. After completion of the reaction, the reaction solution is subjected to conventional post-treatments such as organic solvent extraction and concentration, or further purified by operations such as chromatography and recrystallization, if necessary. Next, 5-(N-acetylamino)-4-fluoro-2-halobenzenethiol [ ] and the general formula YCH ₂ COOH [ ] [where Y represents a chlorine atom or a bromine atom]. ] By reacting haloacetic acid represented by the general formula in a solvent in the presence of a dehydrohalogenating agent at 0°C to 100°C for 0.5 to 24 hours, [In the formula, X represents the same meaning as above. ] A phenylthioglycolic acid derivative represented by the following can be obtained. The amount of reagents used in this reaction is 5-(N-acetylamino)-4-fluoro-
With respect to 1 equivalent of 2-halobenzenethiol [], the amount of haloacetic acid [] is 1.0 to 1.2 equivalents, and the amount of the dehydrohalogenating agent is 1.0 to 1.2 equivalents. As a solvent, aliphatic hydrocarbons such as hexane and heptane, aromatic hydrocarbons such as benzene and toluene,
Examples include ethers such as tetrahydrofuran, acid amides such as N,N-dimethylformamide, sulfur compounds such as dimethyl sulfoxide, water, and mixtures thereof. Examples of the dehydrohalogenation agent include organic bases such as pyridine and triethylamine, and inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, and potassium hydride. After completion of the reaction, the reaction solution is subjected to conventional post-treatments such as solvent extraction and concentration, and if necessary, purified by operations such as chromatography and recrystallization. Furthermore, the phenylthioglycolic acid derivative [] is reacted with 1.0 equivalent to a large excess of mineral acid in a solvent at 20°C to 100°C for 0.5 to 24 hours to deacetylate it. general formula [In the formula, X represents the same meaning as above. ] Aminophenylthioacetic acids represented by these can be obtained. Examples of mineral acids include hydrochloric acid, hydrobromic acid, and sulfuric acid, and examples of solvents include water, alcohol, acetic acid, and the like. After the reaction is completed, the reaction solution is adjusted to pH 1.5 to 4 with an aqueous sodium hydroxide solution, etc. After cooling, the resulting crystals are separated or subjected to usual post-treatments such as organic solvent extraction and concentration, and if necessary. For example, it is purified by operations such as chromatography and recrystallization. The obtained aminophenylthioacetic acid [] and
To this, 1.0 to 1.1 equivalents of 3,4,5,6-tetrahydrophthalic anhydride was added in a solvent at 80°C to 200°C.
By reacting for 0.5 to 12 hours at °C, the general formula [In the formula, X represents the same meaning as above. ] An N-(m-carboxymethylthiophenyl)tetrahydrophthalimide derivative represented by these can be obtained. Examples of the solvent include water, acetic acid, propionic acid, dioxane, etc., and mixtures thereof. After completion of the reaction, the reaction solution is subjected to conventional post-treatments such as organic solvent extraction and concentration, and if necessary, purified by operations such as chromatography and recrystallization. Furthermore, the obtained N-(m-carboxymethylthiophenyl)tetrahydrophthalimide derivative [] has the general formula R-OH [] [wherein R represents the same meaning as above]. ] In a solvent, in the presence of a dehydrating agent, if necessary, in the presence of a base, and if necessary, while removing water from the reaction system, react at 0°C to 200°C for 1 hour to 24 hours. 2-substituted phenyl-4,5,6,7-tetrahydro-2H-isoindole-1,3-dione [] can be obtained by The amount of reagents used in this reaction is N-
For 1 equivalent of (m-carboxymethylthiophenyl)tetrahydrophthalimide derivative [],
The alcohol [ ] is used in an amount of 1 to 10 equivalents, and the dehydrating agent and the base are used in a catalytic amount to 1 equivalent. Examples of solvents include aliphatic hydrocarbons such as hexane, heptane, ligroin, and petroleum ether, aromatic hydrocarbons such as benzene, toluene, and xylene, halogenated hydrocarbons such as chloroform, carbon tetrachloride, and methylene chloride, and diethyl. Examples include ethers such as ether, diisopropyl ether, dioxane, tetrahydrofuran, and diethylene glycol dimethyl ether. Examples of the dehydrating agent include acids such as concentrated sulfuric acid and para-toluenesulfonic acid, and carbodiimides such as dicyclohexylcarbodiimide. Examples of the base include aminopyridines such as 4-N,N-dimethylaminopyridine. After completion of the reaction, the reaction solution is subjected to conventional post-treatments such as organic solvent extraction and concentration, and if necessary, purified by operations such as chromatography and recrystallization. Next, a production example of 2-substituted phenyl-4,5,6,7-sotrahydro-2H-isoindole-1,3-dione [] will be shown as a reference example. Reference example 1 [5-(N-acetylamino)-4-fluoro-
Production of 2-Halobenzenethiol [] 73.25 g of 4-bromo-2-fluoro-5-chlorosulfonylacetanilide was dissolved in 630 ml of acetic acid, and 289.7 g of zinc was added. Heating the reaction solution, 6
Refluxed for an hour. After cooling, water was added, extracted with ethyl acetate, washed with water, washed with sodium bicarbonate, dried, and concentrated to obtain 31.38 g of 2-bromo-4-fluoro-5-acetamino-thiophenol. mp157-158℃ 4-chloro-2-fluoro-5 in the same manner
2-chloro-4-fluoro-5-acetamino-thiophenol mp 156-158°C was obtained from -chlorosulfonylacetanilide. Reference Example 2 [Production of phenylthioglycolic acid derivative []] 8 g of 2-chloro-4-fluoro-5-acetaminothiophenol, 1.6 g of sodium hydroxide,
6 g of bromoacetic acid was added dropwise to a mixture of 25 ml of water at 0 to 5°C, and the mixture was refluxed until it became a lead acetate test paper (-). After cooling, the reaction solution was adjusted to pH=4 and extracted with ethyl acetate. The extract was dried and concentrated to obtain 8.8 g of 5-(N-acetylamino)-2-chloro-4-fluorophenylthioacetic acid. mp145-147℃ In the same manner, 2-bromo-4-fluoro-
From 5-acetaminothiophenol, 5-(N
-acetylamino)-2-bromo-4-fluorophenylthioacetic acid was obtained. mp173.1~174.1
°C Reference Example 3 [Production of aminophenylthioacetic acids] 5-(N-acetylamino)-2-chloro-4-
89.8 g of fluorophenylthioacetic acid was suspended in a 10% aqueous hydrochloric acid solution and heated under reflux for 2 hours. After the reaction solution has cooled down, add sodium hydroxide aqueous solution and adjust the pH to 4.
And so. After cooling with ice, the precipitated crystals were collected, washed with cold water, and air-dried to obtain 55.0 g of 5-amino-2-chloro-4-fluorophenylthioacetic acid. NMR (CDCl ₃ + D ₆ −DMSO) δppm3.55 (2H,
s), 6.75 (1H, d), 6.92 (1H, d), 6.2~
7.6 (2H, m), IRνcm ^-1 (liquid paraffin) 3400, 3300, 1670 In the same manner, 5-(N-acetylamino)-
5-amino-2-bromo-4-fluorophenylthioacetic acid was obtained from 2-bromo-4-fluorophenylthioacetic acid. NMR (CDCl ₃ ) δppm3.6 (2H, s), 6.6 (2H,
m), 6.9 (1H, d), 7.1 (1H, d), IRνcm ^-1 (liquid paraffin) 3380, 3280, 1670 Reference example 4 [N-(m-carboxymethylthiophenyl)
Production of tetrahydrophthalimide derivative [] 55.0 g of 5-amino-2-chloro-4-fluorophenylthioacetic acid and 38.1 g of 3,4,5,6-tetrahydrophthalic anhydride were dissolved in 250 ml of acetic acid.
The mixture was heated under reflux for 1 hour. After the reaction mixture has cooled,
Water was added and extracted with ethyl acetate. After neutralizing the extract with an aqueous sodium bicarbonate solution, washing with water, and drying,
The solvent was distilled off under reduced pressure to give 2-(5-carboxylmethylthio-4-chloro-2-fluorophenyl).
46.8 g of -4,5,6,7-tetrahydro-2H-isoindole-1,3-dione was obtained. mp138-139℃ In the same manner, 5-amino-2-bromo-4
- From fluorophenylthioacetic acid, 2-(5-carboxylmethylthio-4-bromo-2-fluorophenyl)-4,5,6,7-tetrahydro-
2H-isoindole-1,3-dione was obtained. NMR (CDCl ₃ ) δppm1.8 (4H, m), 2.4 (4H,
m), 3.65 (2H, s), 7.28 (1H, d), 7.45
(1H, s), 10.2 (1H, m) IRνcm ^-1 (neat) 1715 Reference example 5 [2-substituted phenyl-4,5,6,7-tetrahydro-2H-isoindole-1,3-dione] ] 2-(4-chloro-2-fluoro-5-carboxymethylthiophenyl)-4,5,6,7-tetrahydro-2H-isoindole-1,3-dione 1.2 g, ethanol 1.0 g Dissolve in 20ml of toluene, add a small amount of p-toluenesulfonic acid, reflux for 3 hours, add water, separate the toluene layer, dry,
Concentrate and purify the residue with a silica gel column to obtain 2-
(4-chloro-2-fluoro-5-ethoxycarbonylmethylthiophenyl)-4,5,6,7,-
Tetrahydro-2H-isoindole-1,3-
0.1 g of dione was obtained. n ¹⁸ _D 1.5670 2-substituted phenyl- which can be produced by a similar method
Some of 4,5,6,7-tetrahydro-2H-isoindole-1,3-dione []
Shown in the table.

【table】

【table】

Claims (1)

[Claims] 1. General formula [In the formula, X represents a chlorine atom or a bromine atom. ] 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonyl chloride. 2 General formula [In the formula, X represents a chlorine atom or a bromine atom. ] A general formula characterized by reacting an alkali metal salt or organic base salt of 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonic acid with phosphorus pentachloride or phosphorus oxychloride. [In the formula, X represents the same meaning as above. ] A method for producing 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonyl chloride. 3 General formula [In the formula, X represents a chlorine atom or a bromine atom. ] The general formula obtained by reacting 2-fluoro-4-haloacetanilide with fuming sulfuric acid [In the formula, X represents the same meaning as above. ] 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonic acid represented by is converted into an alkali metal salt or an organic base salt, and then reacted with phosphorus pentachloride or phosphorus oxychloride. general formula [In the formula, X represents the same meaning as above. ] A method for producing 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonyl chloride. 4 General formula [In the formula, X represents a chlorine atom or a bromine atom. ] The general formula obtained by reacting 2-fluoro-4-haloacetanilide with fuming sulfuric acid [In the formula, X represents the same meaning as above. ] without isolating 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonic acid represented by
General formula characterized by reacting carbon tetrachloride, chloroform or sulfur dichloride [In the formula, X represents the same meaning as above. ] A method for producing 5-(N-acetylamino)-4-fluoro-2-halobenzenesulfonyl chloride.