JP2550619B2 - Process for producing 6-amino-7-fluoro-2H-1,4-benzoxazin-3 (4H) -one - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Field of Industrial Application> The present invention relates to a compound of formula [I] useful as an intermediate, particularly as an intermediate for agricultural chemicals. And a novel method for producing 6-amino-7-fluoro-2H-1,4-benzoxazin-3 (4H) -one represented by

<Prior Art> Conventionally, 2- [4-substituted-7-fluoro-2H-1,4-
Benzoxazin-3 (4H) -one-6-yl] -4,5,
It is known that 6,7-tetrahydro-2H-isoindole-1,3-dione is a compound having a strong herbicidal activity, and the compound is an alkylated or alkenylated compound of the above formula [I]. , Alkynylated or alkoxyalkylated, and then reacted with 3,4,5,6-tetrahydrophthalic anhydride for imidization.

A method for producing a compound represented by the formula [I] which is a starting material compound in that case is described in, for example, JP-A-62-212375, 2.
A method for reductively cyclizing 4-dinitro-5-fluorophenoxyacetic acid or a derivative thereof is known.

<Problems to be Solved by the Invention> However, since the above method uses a dinitrobenzene derivative as a raw material, there is a problem in that handling must be performed with sufficient care in order to carry out the reaction safely.

<Means for Solving Problems> As a result of intensive studies on the production method of the compound represented by the formula [I], the present inventors have found that 4-amino-5-fluoro-2-
The present inventors have found that a compound represented by the formula [I] can be easily produced by reducing nitrophenoxyacetic acid ester with cyclization, and completed the present invention.

In this reaction, the reduction method includes a catalytic reduction method and other chemical reduction methods. In the case of the catalytic reduction method,
Usually, the reaction is carried out at 0 to 150 ° C in the presence of a catalyst such as palladium, platinum, nickel and rhodium. Examples of the solvent used include alcohols such as methanol, ethanol and isopropyl alcohol, 1,2-dichloroethane, 1,
Examples thereof include halogenated hydrocarbons such as 1,1-trichloroethane, dichloromethane and chloroform, aromatic hydrocarbons such as benzene, toluene and xylene. As another chemical reduction method, for example, a method using iron powder can be mentioned. In this case, iron powder is usually used in an amount of 2.25 to 10 mol per mol of 4-amino-5-fluoro-2-nitrophenoxyacetic acid ester, and the treatment is carried out at 50 to 150 ° C. As the reaction solvent, water or a mixture of water and ethyl acetate, methyl isobutyl ketone, or the like is usually used, and acetic acid, hydrochloric acid, sulfuric acid, ferrous chloride, ferric chloride, or the like is usually used as a catalyst. ,, hydrochloric acid and the like may be used as a solvent.

In the above reduction method, the reaction time is generally 30 minutes to 24 hours, and the reaction time is shortened by increasing the reaction temperature.

By carrying out the above reduction reaction, the cyclization reaction proceeds at the same time to produce the desired compound.

After completion of the reaction, the catalyst is removed in the case of the catalytic reduction method and the iron oxide is removed in the case of the reduction method with iron powder, and the solution is subjected to usual post-treatments such as extraction with an organic solvent and concentration. Further, if necessary, operations such as recrystallization and chromatography are performed.

Examples of 4-amino-5-fluoro-2-nitrophenoxyacetic acid ester, which is a starting material for the method of the present invention, include alkyl esters such as methyl ester and ethyl ester, and can be produced by the following route.

[In the formula, R represents an alkyl group. ] That is, 4-amino-3-fluorophenol is reacted with an acetylating agent such as acetyl chloride or acetic anhydride in the presence of a base as necessary to give 4-acetylamino-3-fluorophenol, which is then mixed with chloroacetic acid. , Bromoacetic acid,
A haloacetic acid such as iodoacetic acid is usually reacted in the presence of a dehydrohalogenating agent to give 4-acetylamino-3-fluorophenoxyacetic acid. Next, 4-acetylamino-5-fluoro-2-nitrophenoxyacetic acid is obtained by nitration using nitric acid, a nitrate such as sodium nitrate or potassium nitrate, or a nitrating agent such as a mixture of these with sulfuric acid.

4-Amino-5-fluoro-2-nitrophenoxyacetic acid ester is obtained by reacting 4-acetylamino-5-fluoro-2-nitrophenoxyacetic acid obtained as described above with alcohol to esterify it and at the same time deacetylate it. It is manufactured by converting.

The amount of the reagent to be used in the reaction is usually a catalytic amount to about 5 equivalents relative to 1 equivalent of 4-acetylamino-5-fluoro-2-nitrophenoxyacetic acid, the alcohol is 1 equivalent or more and the solvent. May be used in excess. Examples of the solvent used in this reaction include corresponding alcohols as well as aromatic hydrocarbons such as benzene, toluene and xylene. Further, this reaction can be carried out by an azeotropic dehydration operation if necessary.

The reaction temperature is usually in the range of 50 to 200 ° C., preferably 60 to 110 ° C., and the reaction time is usually 10 minutes to 24 hours.

After completion of the reaction, the reaction solution is poured into water and subjected to usual post-treatments such as extraction with an organic solvent and concentration, and if necessary, operations such as recrystallization and chromatography are performed.

<Effects of the Invention> According to the present invention, a compound of formula [I] useful as an intermediate for agricultural chemicals
The compound represented by is easily produced.

<Examples> Hereinafter, production examples of the present invention will be shown by way of specific examples, but the present invention is not limited to the following examples.

Production Example 1 0.06 g of methyl 4-amino-5-fluoro-2-nitrophenoxyacetate was dissolved in 1 ml of ethanol, 10 mg of 10% palladium carbon was added, and hydrogen was introduced at room temperature. After absorbing a predetermined amount of hydrogen, the catalyst was removed with Celite, and the solution was concentrated to obtain 0.06 g of 6-amino-5-fluoro-2H-1,4-benzoxazin-3 (4H) -one. .

mp 300 ° C or higher NMR δ (CDCl ₃ + DMSO-d ₆ ) 10.2 (1H) 6.7 (1H, d) 6.5 (1H, d) 4.4 (2H) 3.8 (2H) Production Example 2 137 mg of electrolytic iron powder in water 1 ml, acetic acid The mixture was suspended in 1 ml, heated to 90 ° C., and a solution prepared by dissolving 0.06 g of methyl 4-amino-5-fluoro-2-nitrophenoxyacetate in 1 ml of ethyl acetate was added dropwise. After heating under reflux for 4 hours, pass through Celite,
The solution was extracted with ethyl acetate, washed successively with water and aqueous sodium hydrogen carbonate,
Dried and evaporated under reduced pressure to remove the solvent 6-amino-5-fluoro-2H-1,4-benzoxazin-3 (4H) -one 0.04 g
I got

The compound obtained at mp 300 ° C. or higher was identified by NMR with the compound obtained in Production Example 1.

Next, 4-amino-5, which is a starting material of the method of the present invention,
A reference example shows a production example of fluoro-2-nitrophenoxyacetic acid ester.

Reference Example (i) Production of 4-acetylamino-3-fluorophenol 10.1 g of 4-amino-3-fluorophenol was added to 81.
It was dissolved in 49 g, acetic anhydride 8.92 g was added, and the mixture was heated with stirring at 75 ° C. for 2 hours. The reaction solution is allowed to cool, then poured into ice water, extracted with ethyl acetate, washed with water, dried, and then the solvent is distilled off under reduced pressure, and the residue is subjected to silica gel chromatography (developing solvent; ethyl acetate: hexane = 1: 1). Attached, 4-acetylamino-3
-6.3 g of fluorophenol are obtained.

mp 114-115 ° C (ii) Production of 4-acetylamino-3-fluorophenoxyacetic acid 4-Acetylamino-3-fluorophenol was added to a solution prepared by dissolving 1.26 g of baking soda in 5.33 g of water at 30-40 ° C. Stir for 1 hour. To this, a solution prepared by dissolving 1.10 g of sodium hydroxide and 2.28 g of chloroacetic acid in 6.81 g of water was added, and the mixture was stirred at 90 ° C for 2 hours. The reaction mixture was allowed to cool and then adjusted to pH 2 with concentrated hydrochloric acid,
After extraction with ethyl acetate and drying of the extract, the solvent was distilled off under reduced pressure to obtain 2.0 g of 4-acetylamino-3-fluorophenoxyacetic acid.

mp 152-153 ° C (iii) Preparation of 4-acetylamino-5-fluoro-2-nitrophenoxyacetic acid 4-acetylamino-3-fluorophenoxyacetic acid 0.
Suspend 92g in 96% sulfuric acid 14.24g, 0.4% g 61% nitric acid at 0 ℃
Was added dropwise, and the mixture was further stirred for 2 hours at 0 ° C. Then, the reaction mixture was added to ice water, crystals were taken, washed with water, dried, and
1.25 g of acetylamino-5-fluoro-2-nitrophenoxyacetic acid was obtained.

mp 238 to 239 ° C (iv) Production of methyl 4-amino-5-fluoro-2-nitrophenoxyacetate 0.9 g of 4-acetylamino-5-fluoro-2-nitrophenoxyacetic acid was dissolved in 4 g of methanol, and 0.1 g of concentrated sulfuric acid was dissolved. Was added and the mixture was heated under reflux for 14 hours. Next, methanol is distilled off, water is added, the mixture is extracted with ethyl acetate, the extract is washed with water, dried, and the solvent is distilled off under reduced pressure to methyl 4-amino-5-fluoro-2-nitrophenoxyacetate. 0.87 g was obtained.

mp 120-121 ° C

Claims (1)

(57) [Claims] 1. A 6-amino-7-fluoro-2H-1,4-benzoxazine-3 (4H), characterized in that 4-amino-5-fluoro-2-nitrophenoxyacetic acid ester is subjected to reductive cyclization. -On manufacturing method