JPH045013B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the general formula [In the formula, X represents a chlorine atom or a bromine atom. ] The present invention relates to 4-(N-acetylamino)-5-fluoro-1-halo-2-nitrobenzene (hereinafter referred to as the compound of the present invention) represented by the following and a method for producing the same.

The compound of the present invention is reduced, diazotized, reacted with thioglycolic acid, deacetylated, 3,4,
General formula that can be produced by reacting with 5,6-tetrahydrophthalic anhydride and further esterifying [In the formula, R represents a lower alkyl group, a cycloalkyl group, a lower alkynyl group, a halo-lower alkyl group, a lower alkoxycarbonyl lower alkyl group, or a lower alkoxy lower alkyl group, and X represents the same meaning as above. ] 4,5,6,7-tetrahydro-2H represented by
-Isoindole-1,3-dione derivatives do not cause harmful effects on major crops such as corn, wheat, soybean, and rice, and exhibit sufficient herbicidal efficacy against many weeds ( special request
58-86213). The compounds of the present invention are important as intermediates thereof.

The compound of the present invention is a known compound with the general formula [In the formula, X represents the same meaning as above. ] It can be produced by reacting 4-(N-acetylamino)-3-fluoro-1-halobenzene represented by the following with a mixture of fuming nitric acid and fuming sulfuric acid.

To describe the method of the present invention in more detail, 4(N-
After mixing oleum (acetylamino)-3-fluoro-1-halobenzene and fuming sulfuric acid,
The 6-position on the benzene ring of 4-(N-acetylamino)-3-fluoro-1-halobenzene can be selectively nitrated by adding fuming nitric acid and reacting while keeping the temperature at °C. It is.

The amount of reagents used in this reaction is 3 equivalents or more of oleum and 1.0 to 1.5 equivalents of fuming nitric acid per 1 equivalent of 4-(N-acetylamino)-3-fluoro-1-halobenzene. be. Note that the optimum temperature for this reaction is -5°C to 5°C.

After the reaction is complete, pour the reaction solution onto ice, remove the precipitated results, and perform normal post-treatment such as washing with water, or if necessary, purify by chromatography, recrystallization, etc. The desired compound of the present invention is thus obtained.

Examples of manufacturing the compounds of the present invention are shown below. The impurity content in the product was confirmed by gas chromatography under the following conditions.

Detector: Flame ionization detector (FID) Column: 3% OV-101, 1.5m Column temperature: 150℃ for 2 minutes, then heated to 180℃
℃ for 8 minutes Carrier gas: N ₂ , flow rate 50 ml/min. Retention time: 4-(N-acetylamino)-3-fluoro-1-halobenzene [] (raw material)
2.4 min, 4-(N-acetylamino)-5
-Fluoro-1-halo-3-nitrobenzene (impurity) 4.7 minutes, compound of the present invention 6.3 minutes
Production example 50g of 20% oleum was cooled on ice, and 4-(N-acetylamino)-1-chloro-3-fluorobenzene was added.
9.4g was added little by little and dissolved. 3.5 g of fuming nitric acid was gradually added while maintaining the temperature at 0-5°C. 0~
After stirring for 1 hour at 5°C, the reaction mixture was poured onto 50 g of ice. The precipitated crystals were collected, washed with water, air-dried, and
11.6 g of (N-acetylamino)-1-chloro-5-fluoro-2-nitrobenzene was obtained. mp124.7
℃-125.7℃ 4-(N-acetylamino)-1-bromo-5-fluoro-2-nitrobenzene was obtained in the same manner. mp139.6°C-140.6°C No raw materials or impurities were detected in either case.

In addition, from the compound of the present invention, by the following method,
A 4,5,6,7-tetrahydro-2H-isoindole-1,3-dione derivative [] having herbicidal activity can be obtained.

That is, by reacting the compound of the present invention and iron powder in a solvent in the presence of an acid and reducing it, the general formula [In the formula, X represents the same meaning as above. ] After obtaining the alinine derivative represented by the formula and further diazotizing it using sodium nitrite, thioglycolic acid and a divalent copper salt were reacted to form the general formula [In the formula, X represents the same meaning as above. ] By obtaining the phenylthioacetic acid represented by the formula and deacetylating it in a solvent using a mineral acid, the general formula [In the formula, X represents the same meaning as above. ] By obtaining the aminophenylthioacetic acid represented by the formula and then reacting it with 3,4,5,6-tetrahydrophthalic anhydride in a solvent, the general formula [In the formula, X represents the same meaning as above. ] A substituted phenylthioacetic acid represented by the following was obtained, and this was combined with the general formula R-OH [ ] [wherein R represents the same meaning as above. ] The desired 4,5,6,7-tetrahydro-
A 2H-isoindole-1,3-dione derivative [] can be obtained.

Standard reaction conditions for the above method are described below.

When obtaining the aniline derivative [ ] from the compound of the present invention, the reaction temperature is 50°C to 100°C, and the amount of iron powder used is 2.5 to 100°C per equivalent of the compound of the present invention.
10 equivalents, examples of the acid include acetic acid, and examples of the solvent include ethyl acetate, acetic acid, ethanol, water, etc.

When obtaining phenylthioacetic acids [ ] from aniline derivatives [ ], diazotization is a common method, and the amount of sodium nitrite used is 1.0 to 1.5 equivalents per equivalent of aniline derivatives [ ]. In addition, the reaction temperature when introducing thioglycolic acid is
20°C to 40°C, the amounts of thioglycolic acid and divalent copper salt used are 1.0 to 1.5 equivalents and 1.0 to 1.2 equivalents, respectively, per equivalent of aniline derivative [].
Examples of divalent copper salts include copper sulfate and copper carbonate.

When obtaining aminophenylthioacetic acids [ ] from phenylthioacetic acids [ ], the reaction temperature is 20°C to 100°C, and the amount of mineral acid used is 1.0 equivalent to a large amount per equivalent of phenylthioacetic acids [ ]. This is an excessive amount, and mineral acids include hydrochloric acid, sulfuric acid, etc., and solvents include alcohol, water, etc.

When obtaining substituted phenylthioacetic acid [ ] from aminophenylthioacetic acids [ ], the reaction temperature is 80°C to 200°C, and the amount of 3,4,5,6-tetrahydrophthalic anhydride is The amount is 1.0 to 1.1 equivalent to 1 equivalent of acetic acid, and examples of the solvent include acetic acid, water, dioxane, and propionic acid.

Substituted phenylthioacetic acid [] to 4,5,6,
7-tetrahydro-2H-isoindole-1,
When obtaining the 3-dione derivative [],
The reaction temperature is 0°C to 200°C, the amounts of alcohol [ ], dehydrating agent and base used are 1 to 10 equivalents each, catalytic amount - 1 equivalent, catalyst amount - 1 equivalent, and the dehydrating agent is concentrated sulfuric acid, para-toluenesulfonic acid,
Examples of the base include dicyclohexylcarbodiimide and the like, and examples of the base include 4-N,N-dimethylaminopyridine.

Next, 4,5,6,7-tetrahydro-2H-
A production example of isoindole-1,3-dione derivative [] is shown as a reference example.

Reference Example 1 31.9 g of iron powder was suspended in 60 ml of 5% acetic acid aqueous solution. This was heated to 90°C, and a mixed solution of 13.3 g of 4-(N-acetylamino)-1-chloro-5-fluoro-2-nitrobenzene in 100 ml of acetic acid and 70 ml of ethyl acetate was added dropwise. After heating under reflux at 80°C for 2 hours, the residue was removed through Celite. Organic matter was extracted from the liquid with ethyl acetate, and the extract was neutralized with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was washed with water, dried, and the solvent was distilled off under reduced pressure to give 4-(N-acetylamino).
7.0 g of -2-amino-1-chloro-5-fluorobenzene was obtained. mp140.5°C-141.5°C 4-(N-acetylamino)-2-amino-1-bromo-5-fluorobenzene was produced in the same manner. mp146.8℃－147.8℃ Reference example 2 4-(N-acetylamino)-2-amino-1-
7.0 g of chloro-5-fluorobenzene was dissolved in concentrated hydrochloric acid (9 g).
ml, suspended in 40 ml of water and 60 g of ice. Suspension -
While maintaining the temperature at 5 to 10°C, preferably 0 to 5°C, a solution of 2.5 g of sodium nitrite dissolved in 8 ml of water was gradually added dropwise. After the dropwise addition, the mixture was stirred at the same temperature for 1 hour, and the suspension disappeared and the mixture became a solution. Sulfamic acid was added to the diazonium solution thus prepared.
Added 0.2g. Meanwhile, in another container, 4.1 g of thioglycolic acid, 2.3 g of basic copper carbonate, and 34 ml of water were mixed and stirred for 30 minutes at 15 to 25°C. To this, a diazonium solution containing sulfamic acid was immediately added. After stirring for 30 minutes, 8.4 ml of 50% aqueous sodium hydroxide solution was gradually added dropwise to adjust the pH to 7-8, and the pH was adjusted to 95-8.
The mixture was heated and stirred at 100°C for 1 hour. The reaction mixture was heated through Celite to remove the copper salt. After adding 12 ml of concentrated hydrochloric acid to the solution to make it acidic, it was extracted with ethyl acetate. After drying, the solvent was distilled off under reduced pressure, and 5-(N
4.8 g of -acetylamino)-2-chloro-4-fluorophenylthioacetic acid was obtained. mp145.0~147.0
5-(N-acetylamino)-2-bromo-4-fluorophenylthioacetic acid was produced in the same manner. mp173.1～174.1℃ Reference example 3 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
It was set as 4. After cooling on ice, the precipitated crystals were collected, washed with cold water, air-dried, and 5-amino-2-chloro-4-
55.0 g of fluorophenylthioacetic acid was obtained. m.
p.300℃ or higher NMR (CDCl ₃ +D ₆ −DMSO)
δppm3.55 (2H, s), 6.75 (1H, d), 6.92 (1H,
d), 6.2-7.6 (2H, m); IRvcm ^-1 (liquid paraffin) 3400, 3300, 1670 5-amino-2-bromo-4-fluorophenylthioacetic acid was produced in the same manner. mp300℃ or higher 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 55.0 g of 5-amino-2-chloro-4-fluorophenylthioacetic acid Dissolve 38.1 g of 3,4,5,6-tetrahydrophthalic anhydride 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, and 2-(5-carboxymethylthio-4-chloro-2-fluoro)phenyl-
46.8 g of 4,5,6,7-tetrahydro-2H-isoindole-1,3-dione was obtained. mp138
-139℃ Similarly, 2-(5-carboxymethylthio-
4-bromo-2-fluoro)phenyl-4,5,
6,7-tetrahydro-2H-isoindole-
1,3-dione was produced. Glassy Reference Example 5 2-(4-chloro-2-fluoro-5-carboxymethylthiophenyl)-4,5,6,7-tetrahydro-2H-isoindole-1,3-dione 1.2 g, ethanol 1.0 g was dissolved in 20 ml of toluene, a small amount of p-toluenesulfonic acid was added, refluxed for 3 hours, water was added, the toluene layer was separated, dried and concentrated, and the residue was purified 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

Claims (1)

[Claims] 1. General formula [In the formula, X represents a chlorine atom or a bromine atom. ] 4-(N-acetylamino)-5-fluoro-1-halo-2-nitrobenzene. 2 General formula [In the formula, X represents a chlorine atom or a bromine atom. ] General formula characterized by reacting 4-(N-acetylamino)-3-fluoro-1-halobenzene represented by with a mixture of fuming nitric acid and fuming sulfuric acid to nitrate it. [In the formula, X represents the same meaning as above. ] A method for producing 4-(N-acetylamino)-5-fluoro-1-halo-2-nitrobenzene.