KR100212636B1 - New process for preparing herbicidal pyrimidyloxybenzoic acid oxime ester derivatives - Google Patents

Abstract

The present invention provides a substituted 5- (4,6-dimethoxypyrimidin-2-yl) oxy-4H- (1,3) -benzodioxin-4-one derivative of the general formula (IV) in the first step. Is reacted with an oxime of formula (III) or a metal salt thereof, and the compound of formula (V) produced in the second step is reacted with a pyrimidine derivative of formula (VI). To a method for preparing an oxime ester derivative of 2,6-di (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid:

Wherein R is hydrogen, halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₃ -C ₆ cycloalkyl, C ₁ -C ₄ alkoxy, C ₂ -C ₄ alkenyloxy, C ₁ -C ₄ Alkylthio, amino, aryl, aryloxy, C ₁ -C ₄ acyl or C ₁ -C ₄ acyloxy which may be substituted by C ₁ -C ₄ alkyl, n represents an integer from 1 to 5, R ₂ is hydrogen, halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio, C ₁ -C ₄ alkoxycarbonyl, C ₂ -C ₄ alkenyloxy Carbonyl, arylmethoxycarbonyl, heteroarylmethoxycarbonyl, C ₁ -C ₄ alkylaminocarbonyl, arylmethylaminocarbonyl, heteroarylmethylaminocarbonyl, or aryl, R ₃ and R ₄ are Each independently hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₂ haloalkyl having 1 to 5 halogen atoms, or 1 to 5 halogen atoms and / or C ₁ -C ₄ alkyl, C ₁ -C ₄ Alkoxy, C ₁ -C ₂ haloalkyl and ni C ₂ -C ₆ alkyl, which represents phenyl which may contain one or two groups selected from the group, or R ₃ and R ₄ together may be substituted by 1 to 5 halogen atoms and / or C ₁ -C ₄ alkyl A ren chain, R represents hydrogen or an alkali metal cation, Z represents halogen, C ₁ -C ₄ alkylsulfonyl or arylsulfonyl.

Description

Novel Process for Preparation of Herbicidal Pyrimidyloxybenzoic Acid Oxime Esters

The present invention relates to a novel process for preparing pyrimidyloxybenzoic acid oxime ester derivatives having herbicidal activity. More specifically, the present invention provides a novel method for preparing an oxime ester derivative of 2,6-di (4,6-dimethoxypyrimidin-2-yl) oxybanzo acid represented by the following general formula (1). It is about.

Wherein R ₁ is hydrogen, halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₃ -C ₆ cycloalkyl, C ₁ -C ₄ alkoxy, C ₂ -C ₄ alkenyloxy, C ₁ -C ₄ alkylthio, amino, aryl, aryloxy, C ₁ -C ₄ acyl or C ₁ -C ₄ acyloxy which may be substituted by C ₁ -C ₄ alkyl, n represents an integer from 1 to 5, R ₂ is hydrogen, halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio, C ₁ -C ₄ alkoxycarbonyl, C ₂ -C ₄ alkenyl oxycarbonyl, aryl-methoxy-carbonyl, heteroaryl, methoxycarbonyl, C ₁ -C ₄ alkyl-aminocarbonyl, aryl-aminocarbonyl-methyl, heteroaryl-methylamino represents a carbonyl, or an aryl group.

In the definition of the above substituents, the term alkyl, when used alone or as a compound term such as alkylthio or alkylaminocarbonyl, or means a straight or branched chain saturated hydrocarbon radical such as methyl, ethyl, n-propyl, isopropyl or various butyl isomers, etc. And alkoxy means methoxy, ethoxy, n-propoxy, isopropoxy or various butoxy isomers, alkenyl when used alone or when used as a compound word such as alkenyloxy or vinyl, 1-propenyl Means straight or branched alkene such as, 2-propenyl and various butenyl isomers, and acyl refers to acetyl, propionyl, butanoyl, etc., when used alone or in synthetic terms such as acyloxy, and halogen is fluorine. , Chlorine, bromine or iodine, aryl when used alone or aryloxy or arylmethoxy Viterbo means carbonyl optionally substituted phenyl or when used by the C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, one to five halogen, such as a compound word, and H. kerosene aryl or when used alone heteroaryl methoxycarbonyl Or a 5- or 6-membered aromatic hydrocarbon containing 1 to 3 oxygen, sulfur or nitrogen atoms when used as a compound word such as heteroarylmethylaminocarbonyl.

Compounds of the general formula (1) exhibit a wide range of excellent herbicidal effect over the weeds, broadleaf weeds or annual weeds or perennial weeds, and is particularly excellent in controlling the annual and perennial weeds, including blood, for direct sowing rice. The inventors have applied for a new material and / or a method for manufacturing the same (see Korean Patent Application No. 93-31016).

According to the above patent, the benzoic acid compound of the structural formula (II) substituted 2, 6 positions is esterified with an oxime of aryl ketone as shown in Scheme A below to obtain the target compound of general formula (I),

Wherein R ₁ , R ₂ and n are as defined above.

However, the benzoic acid compound of the structural formula (II) substituted at positions 2 and 6 used as a starting material in the reaction of Scheme A has an ester with a three-dimensionally large aryl ketone oxime since the carboxyl group is severely hidden in three dimensions. Conventional reactions in the reaction may be limited in reactivity or the use of uneconomic special reaction conditions.

Accordingly, the present inventors conducted intensive research to find a more direct and efficient method for solving the above-described disadvantages of the manufacturing method of the prior art, and as a result, substituted 5- (4) represented by the following general formula (IV): By using the 6-dimethoxypyrimidin-2-yl) oxy-4H- (1,3) -benzodioxin-4-one derivative as a starting material, the general formula can be obtained in excellent yield without using special reaction conditions. It was found that the target compound of I) can be prepared and the present invention has been completed.

Wherein R ₃ and R ₄ are each independently hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₂ haloalkyl having 1 to 5 halogen atoms, or 1 to 5 halogen atoms and / or C _1- Phenyl which may contain one or two groups selected from C ₄ alkoxy, C ₁ -C ₂ haloalkyl and nitro, or R ₃ and R ₄ together represent 1 to 5 halogen atoms and / or C ₁ -C ₄ A C ₂ -C ₆ alkylene chain which may be substituted by alkyl. Accordingly, the present invention provides a substituted 5- (4,6-dimethoxypyrimidin-2-yl) oxy-4H- (1,3) -benzodioxin-4-one derivative of the general formula (IV). It is used as a release material and reacts with the oxime of general formula (III) or its metal salt, and the compound of general formula (V) which is a product is reacted with the pyrimidine derivative of general formula (VI), An improved process for preparing oxime ester derivatives of, 6-di (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid.

The process according to the invention can be represented by the following scheme (B).

R ₁ to R ₄ in the scheme are as defined above, Z represents halogen, C ₁ -C ₄ alkylsulfonyl or arylsulfonyl, and R represents hydrogen or an alkali metal cation. According to the method of the present invention shown in Scheme B, first, substituted 5- (4,6-dimethoxypyrimidin-2-yl) oxy-4H- represented by general formula (IV) in the first step The (1,3) -benzodioxin-4-one derivative is reacted with an oxime compound of formula (III) or a metal salt thereof, and then the compound of formula (V) produced is subjected to the formula (VI) in the second step. Reaction with a pyrimidine derivative of affords the desired compound (I). Hereinafter, the manufacturing method of the present invention will be described in detail. According to the method of Scheme B, first, in the first step, the substituted 5- (4,6-dimethoxypyrimidin-2-yl) oxy-4H- (1,3) -benzodioxin-4-one derivative (IV) is reacted with an oxime compound (III) to ring-open the benzodioxine to produce a compound of formula (VI).

This reaction can preferably be carried out in the presence of a solvent. Suitable solvents for this purpose include, for example, ethers such as tetrahydrofuran and diethyl ether, polar solvents such as dimethylformamide and dimethyl sulfoxide, halogenated hydrocarbons such as dichloromethane and carbon tetrachloride and benzene and toluene. One or two or more solvents selected from aromatic hydrocarbons can be used, of which tetrahydrofuran or dimethylpodamide is preferred. The reaction of the first step can also be carried out in the presence or absence of a base. Suitable bases for the first stage reaction may include inorganic bases such as potassium carbonate, sodium carbonate, sodium hydride, sodium hydrogen carbonate, and preferably potassium carbonate or sodium hydride. The reaction temperature may be changed in the range of room temperature to 150, but the reaction is preferably performed at a temperature of 50 to 80 ℃.

The oxime compound of formula (III), in which the reactant is also used in the first stage reaction, may be used in the form of a metal salt in which R is metal (M). When the compound of formula (3) is used in the form of an oxime metal salt, this oxime metal salt can be prepared by reacting the corresponding oxime (III) (R = H) with the corresponding metal compound in the presence of a base and a solvent. have. Suitable bases for this reaction include inorganic bases such as potassium carbonate, sodium carbonate, sodium hydride and sodium hydrogen carbonate, sodium alkoxides such as sodium methoxide, sodium ethoxide and sodium t-butoxide, and the like. Potassium carbonate or sodium hydride is used. In this reaction, solvents include ethers such as tetrahydrofuran and diethyl ether, polar solvents such as dimethylformamide and dimethyl sulfoxide, halogenated hydrocarbons such as dichloromethane and carbon tetrachloride and aromatic hydrocarbons such as benzene and toluene. One or two or more solvents selected may be used, of which tetrahydrofuran or dimethylformamide is particularly preferred.

After completion of the first stage reaction, the compound of formula (V) produced is reacted with the pyrimidine derivative of formula (VI) in the second stage to give the desired compound of formula (I). In this case, the compound of the general formula (V) produced in the first step may be reacted with pyrimidine derivative (VI) continuously without being separated from the reaction compound, or purified from the reaction mixture after purification by discontinuous process. You may react with (VI). When product (V) is reacted with pyrimidine derivative (VI) by a continuous process, the reaction mixture obtained in the first step is added dropwise to the solution of pyrimidine derivative (VI) or vice versa. The process can be carried out in either of two ways, in which a solution of is added dropwise directly to the reaction mixture. The second stage reaction is preferably carried out in a solvent. Suitable solvents for this reaction include ethers such as tetrahydrofuran and diethyl ether, polar solvents such as dimethylformamide and dimethyl sulfoxide, halogenated hydrocarbons such as dichloromethane and carbon tetrachloride and aromatic hydrocarbons such as benzene and toluene. One or two or more solvents selected from among them can be used, and preferably tetrahydrofuran or dimethylformamide is used. The solvent in this reaction is generally preferably the same as used in the first step, but is not necessary.

The second stage reaction can also be carried out in the presence or absence of a base. Examples of bases that can be used for this purpose may include inorganic bases such as potassium carbonate, sodium carbonate, sodium hydride, sodium hydrogen carbonate, and preferably potassium carbonate or sodium hydride.

The second step reaction may be generally carried out at a temperature range of room temperature to 150 ° C., and preferably at 50 to 80 ° C.

According to the method of the present invention as described above, the desired herbicidal pyrimidyloxybenzoic acid oxime ester derivative of the general formula (I) can be easily obtained in excellent yield under mild reaction conditions.

Hereinafter, the present invention will be described in more detail with reference to Preparation Examples and Examples. However, these preparation examples and examples are merely to aid the understanding of the present invention, and the scope of the present invention in any sense is not limited thereto.

[Production Example 1]

[Synthesis of Acetophenone Oxime Sodium Salt]

4.8 g of 60% sodium hydride and tetrahydrofuran 300 Temperature in the mixture of 5 12 g of acetophenone oxime was slowly added while maintaining below, and stirred at room temperature for 20 minutes. The reaction mixture was distilled off under reduced pressure to obtain 13 g of a white title compound (yield: 93.7%).

Example 1

[Synthesis of 2,6-di (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid acetophenone oxime ester]

Dimethylformamide solution 100 of 27.0 g of 5- (4,6-dimethoxypyrimidin-2-yl) oxy-2,2-dimethyl-4H- [1,3] -benzodioxin-4-one 100 13 g of acetophenone oxime sodium salt obtained in Preparation Example 1 was added to dimethylformamide 40. It was dissolved in and added dropwise at room temperature and stirred for 30 minutes. The reaction mixture was mixed with 1,8 g of 4,6-dimethoxy-2-methylsulfonylpyrimidine and 11.4 g of potassium carbonate, in a mixture of dimethylformhamide 60 Dropped in Reaction temperature 80 to 85 After stirring for 1 hour while maintaining the solvent, the solvent was distilled off under reduced pressure. The organic layer extracted by adding water and dichloromethane was dried over anhydrous sodium sulfate, distilled under reduced pressure and recrystallized with acetone to obtain a white solid compound 24g.

Example 2

[Synthesis of 2,6-di (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid benzophenone oxime ester]

5.0 g of 60% sodium hydride and 38 g of 5- (4,6-dimethoxypyrimidin-2-yl) oxy-2-phenyl-4H- [1,3] -benzodioxin-4-one are dimethylformamide 100 Putting on 5 Was maintained. Benzophenone oxime 19.7 g dimethylformamide solution 40 Was added dropwise and stirred at room temperature for 20 minutes. After the reaction was completed, the whole mixture was mixed with 21.8 g of 4,6-dimethoxy-2-methylsulfonylpyrimidine and 1.3 g of potassium carbonate. Dropped in Reaction temperature is 80 After stirring for 2 hours while distilling under reduced pressure, the solvent was distilled under the same procedure as in Example 1 to obtain 38 g of the title compound.

Example 3

[Synthesis of 2,6-di (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid benzaldoxime ester]

5.0 g of 60% sodium hydride and 33.2 g of 5- (4,6-dimethoxypyrimidin-2-yl) oxy-2,2-dimethyl-4H- [1,3] -benzodioxin-4-one Dimethylformamide 10 And add the reaction temperature to 5 Was maintained. Here is benzaldehyde oxime 12.1 g dimethylformamide solution 40 Was added dropwise and stirred at room temperature for 20 minutes. After the reaction was completed, the entire mixture was mixed with 21.8 g of 4,6-dimethoxy-2-methylsulfonylpyrimidine and 1.3 g of potassium carbonate. Dropped in Reaction temperature is 80 After stirring for 2 hours and distilling under reduced pressure, the solvent was distilled off in the same manner as in Example 1 to obtain 42.1 g of the title compound.

Example 4

[Synthesis of 2,6-di (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid 4-nitrobenz aldoxime ester]

5.0 g of 60% sodium hydride and 38 g of 5- (4,6-dimethoxypyrimidin-2-yl) oxy-2,2-dimethyl-4H [1,3] -benzodioxin-4-one are dimethylform Amide 150 And add the reaction temperature to 5 Was maintained. Here, 16.6 g of 4-nitrobenz aldoxime solution of dimethylformamide 40 Was added dropwise and the reaction temperature was raised to room temperature and stirred for 20 minutes. 21.8 g of 4,6-dimethoxy-2-methylsulfonylpyrimidine and 1.3 g of potassium carbonate were added to the reaction mixture, and 80 to 85 Heated to and stirred for 3 to 4 hours. The solvent was distilled off under reduced pressure and the same procedure as in Example 1 was carried out to obtain 39.9 g of the title compound.

Example 5

[Synthesis of 2,6-di (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid 4-methoxybenz aldoxime ester]

5.0 g of 60% sodium hydride and 300 of tetrahydrofuran 15.1 g of 4-methoxybenz aldoxim was added thereto, and the mixture was stirred at room temperature for 20 minutes. 38.0 g of 5- (4,6-dimethoxypyrimidin-2-yl) oxy-2-phenyl-4H- [1,3] -benzodioxin-4-one was added to the reaction mixture, which was further stirred at room temperature for 20 minutes. After stirring, the mixture was distilled under reduced pressure to obtain a sodium salt of 2- (4,6-dimethoxypyrimidin-2-yl-oxy) -6-hydroxybenzoic acid 4-methoxybenz aldoxime ester. The organic layer obtained by extracting the solid salt with water and dichloromethane was dried over anhydrous sodium sulfate and distilled under reduced pressure. Dimethylformamide 100 without further separation and purification After letting it on, 80 Dimethylformamide mixture of 1.3 g of potassium carbonate and 21.8 g of 4,6-dimethoxy-2-methylsulfonylpyrimidine Dropped in Reaction temperature 80 to 85 The mixture was stirred for 1 hour while maintaining the solvent and the solvent was distilled under reduced pressure, followed by the same procedure as in Example 1 to obtain 35 g of the title compound.

The physical and spectroscopic properties of the compounds obtained in Examples 1 to 5 are as specified in the above-mentioned Korean Patent Application No. 93-31016.

Claims (7)

Substituted 5- (4,6-dimethoxypyrimidin-2-yl) oxy-4H- (1,3) -benzodioxin-4-one derivative of general formula (IV) in the first step Reacting with the oxime of (III) or a metal salt thereof, and reacting the compound of formula (5) generated in the second step with a pyrimidine derivative of formula (VI), 2, Process for preparing oxime ester derivatives of 6-di (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid: Wherein R ₁ is hydrogen, halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₃ -C ₆ cycloalkyl, C ₁ -C ₄ alkoxy, C ₂ -C ₄ alkenyloxy, C ₁ -C ₄ Alkylthio, amino, aryl, aryloxy, C ₁ -C ₄ acyl or C ₁ -C ₄ acyloxy which may be substituted by C ₁ -C ₄ alkyl, n represents an integer from 1 to 5, R ₂ is hydrogen, halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio, C ₁ -C ₄ alkoxycarbonyl, C ₂ -C ₄ alkenyloxy Carbonyl, arylmethoxycarbonyl, heteroarylmethoxycarbonyl, C ₁ -C ₄ alkylaminocarbonyl, arylmethylaminocarbonyl, heteroarylmethylaminocarbonyl, or aryl, R ₃ and R ₄ are Each independently hydrogen, C ₁ -C ₄ alkyl, C ₁ -C ₂ haloalkyl having 1 to 5 halogen atoms, or 1 to 5 halogen atoms and / or C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₂ haloalkyl, and Represents a phenyl which may contain 1 or 2 groups selected from Trojan or, R ₃ and R ₄ is C ₂ -C _6, which may be substituted by 1 to 5 halogen atoms and / or C ₁ -C ₄ alkyl with Alkylene chain and R represents hydrogen or an alkali metal cation and Z represents halogen C ₁ -C ₄ alkylsulfonyl or arylsulfonyl. The method of claim 1, characterized in that the first step reaction is carried out in the presence of at least one solvent selected from the group consisting of tetrahydrofuran, diethyl ether, dimethylformamide, dimethylsulfoxide, dichloromethane, carbon tetrachloride, benzene and toluene. How to. The process of claim 1, wherein the first step reaction is carried out in the presence of an inorganic base selected from the group consisting of potassium carbonate, sodium carbonate, sodium hydride and sodium hydrogen carbonate. The method of claim 1, wherein after completion of the first stage reaction, the compound of general formula (V) is reacted with pyrimidine derivative (VI) continuously without separation from the reaction mixture. The method of claim 1, characterized in that the second step reaction is carried out in the presence of at least one solvent selected from the group consisting of tetrahydrofuran, diethyl ether, dimethylformamide, dimethylsulfoxide, dichloromethane, carbon tetrachloride, benzene and toluene. How to. The method of claim 1, wherein the second step reaction is carried out in the presence of an inorganic base selected from the group consisting of potassium carbonate, sodium carbonate, sodium hydride and sodium hydrogen carbonate. The method of claim 1, wherein the reaction is performed at room temperature to 150. Characterized in that performed in the temperature range of.