Preparation method of 2-chloro-3-alkoxymethyl-4-methylsulfonylbenzoic acid

Abstract

The invention relates to a preparation method of 2-chloro-3-alkoxymethyl-4-methylsulfonylbenzoic acid. The method comprises the following steps of: carrying out an esterolysis reaction on a raw material methyl 2-chloro-3-bromomethyl-4-methanesulfonylbenzoate in a tertiary alcohol solvent in the presence of an alkaline substance to obtain 2-chloro-3-bromomethyl-4-methanesulfonylbenzoate; and reacting 2-chloro-3-bromomethyl-4-methylsulfonylbenzoate with alcohol in the presence of an alkaline substance or reacting 2-chloro-3-bromomethyl-4-methylsulfonylbenzoate with alkali metal alkoxide to obtain the 2-chloro-3-alkoxy methyl-4-methylsulfonylbenzoic acid. According to the preparation method provided by the invention, tertiary alcohol is used as a solvent, and the raw materials are subjected to an esterolysis reaction in the presence of an alkaline substance, so that the content of impurities is reduced, the yield and the quality of a target compound are greatly improved, and a guarantee is provided for finally synthesizing high-quality tembotrione and tefuryltrione technical materials.

Description

technical field

[0001] The invention belongs to the field of synthesis of fine chemical intermediates, and relates to a preparation method of 2-chloro-3-alkoxymethyl-4-methylsulfonylbenzoic acid, in particular to 2-chloro-3-(2,2,2 - Preparation of -trifluoroethoxy)methyl-4-methylsulfonylbenzoic acid and 2-chloro-3-[(RS)-tetrahydrofuran-2-ylmethoxymethyl]-4-methylsulfonylbenzoic acid method. Background technique

[0002] 4-Hy-droxyphenylpyruvate dioxygenase (HPPD) is currently one of the most important herbicide targets, and HPPD inhibitor herbicides occupy an important position among the 18 types of herbicides in the world. Accounting for 5.8% of the global herbicide market, this type of agent is known for its broad-spectrum, high efficiency, and slow development of resistance. HPPD inhibitor herbicides have the same mechanism of action, but are not completely related in structure, including triketones, pyrazolones and isoxazolones. Tembotrione and Tefuryltrione are HPPD ...

Examples

Embodiment 1

[0065] (1) The preparation of 2-chloro-3-bromomethyl-4-methanesulfonyl benzoate, main reaction process can be expressed with following reaction equation:

[0066]

[0067] Add 200 mL of tert-butanol into the reaction flask, start stirring, drop 8.8 g of sodium hydroxide (48%, 0.105 mol) into it at room temperature, and after the sodium hydroxide is uniformly dispersed, control the temperature of the kettle at 25° C., add 34.8 g of 2-Chloro-3-bromomethyl-4-methylsulfonylbenzoic acid methyl ester (98%, 0.1mol) was poured into the kettle for alkaline hydrolysis reaction, the reaction process was slightly exothermic, the temperature of the kettle was controlled at 25°C, and the reaction was carried out for 7 hours . After the reaction was completed, the normalized content of 2-chloro-3-bromomethyl-4-methanesulfonylbenzoic acid sodium salt in liquid chromatography was 98.2%, and the solvent was removed under negative pressure and used directly for the subsequent etherification r...

Embodiment 2

[0073] (1) The preparation of 2-chloro-3-bromomethyl-4-methanesulfonyl benzoate, main reaction process can be expressed with following reaction equation:

[0074]

[0075] Add 200 mL of tert-amyl alcohol to the reaction flask, start stirring, drop 8.8 g of sodium hydroxide (48%, 0.105 mol) into it at room temperature, and after the sodium hydroxide is uniformly dispersed, control the temperature of the kettle at 25 ° C, and add 34.8 g of 2-Chloro-3-bromomethyl-4-methylsulfonylbenzoic acid methyl ester (98%, 0.1mol) was poured into the kettle for alkaline hydrolysis reaction, the reaction process was slightly exothermic, the temperature of the kettle was controlled at 25°C, and the reaction was carried out for 7 hours . After the reaction was completed, the normalized content of 2-chloro-3-bromomethyl-4-methanesulfonylbenzoic acid sodium salt in liquid chromatography was 97.8%, and the solvent was removed under negative pressure and used directly for the subsequent etherific...

Embodiment 3

[0081] (1) The preparation of 2-chloro-3-bromomethyl-4-methanesulfonyl benzoate, main reaction process can be expressed with following reaction equation:

[0082]

[0083] Add 70 mL of tert-butanol into the reaction bottle, start stirring, drop 14 g of sodium hydroxide (30%, 0.105 mol) into it at room temperature, after the sodium hydroxide is uniformly dispersed, control the temperature of the kettle at 30 ° C, and add 34.8 g of 2 -Chloro-3-bromomethyl-4-methylsulfonylbenzoic acid methyl ester (98%, 0.1mol) was poured into the kettle for alkaline hydrolysis reaction, the reaction process was slightly exothermic, the temperature of the kettle was controlled at 30°C, and the reaction was carried out for 12 hours. After the reaction was completed, the normalized content of 2-chloro-3-bromomethyl-4-methanesulfonylbenzoic acid sodium salt in liquid chromatography was 92.5%, and the solvent was removed under negative pressure and used directly for the subsequent etherification re...

technical field

[0001] The invention belongs to the field of synthesis of fine chemical intermediates, and relates to a preparation method of 2-chloro-3-alkoxymethyl-4-methylsulfonylbenzoic acid, in particular to 2-chloro-3-(2,2,2 - Preparation of -trifluoroethoxy)methyl-4-methylsulfonylbenzoic acid and 2-chloro-3-[(RS)-tetrahydrofuran-2-ylmethoxymethyl]-4-methylsulfonylbenzoic acid method. Background technique

[0002] 4-Hy-droxyphenylpyruvate dioxygenase (HPPD) is currently one of the most important herbicide targets, and HPPD inhibitor herbicides occupy an important position among the 18 types of herbicides in the world. Accounting for 5.8% of the global herbicide market, this type of agent is known for its broad-spectrum, high efficiency, and slow development of resistance. HPPD inhibitor herbicides have the same mechanism of action, but are not completely related in structure, including triketones, pyrazolones and isoxazolones. Tembotrione and Tefuryltrione are HPPD ...

Examples

Embodiment 1

[0065] (1) The preparation of 2-chloro-3-bromomethyl-4-methanesulfonyl benzoate, main reaction process can be expressed with following reaction equation:

[0066]

[0067] Add 200 mL of tert-butanol into the reaction flask, start stirring, drop 8.8 g of sodium hydroxide (48%, 0.105 mol) into it at room temperature, and after the sodium hydroxide is uniformly dispersed, control the temperature of the kettle at 25° C., add 34.8 g of 2-Chloro-3-bromomethyl-4-methylsulfonylbenzoic acid methyl ester (98%, 0.1mol) was poured into the kettle for alkaline hydrolysis reaction, the reaction process was slightly exothermic, the temperature of the kettle was controlled at 25°C, and the reaction was carried out for 7 hours . After the reaction was completed, the normalized content of 2-chloro-3-bromomethyl-4-methanesulfonylbenzoic acid sodium salt in liquid chromatography was 98.2%, and the solvent was removed under negative pressure and used directly for the subsequent etherification r...

Embodiment 2

[0073] (1) The preparation of 2-chloro-3-bromomethyl-4-methanesulfonyl benzoate, main reaction process can be expressed with following reaction equation:

[0074]

[0075] Add 200 mL of tert-amyl alcohol to the reaction flask, start stirring, drop 8.8 g of sodium hydroxide (48%, 0.105 mol) into it at room temperature, and after the sodium hydroxide is uniformly dispersed, control the temperature of the kettle at 25 ° C, and add 34.8 g of 2-Chloro-3-bromomethyl-4-methylsulfonylbenzoic acid methyl ester (98%, 0.1mol) was poured into the kettle for alkaline hydrolysis reaction, the reaction process was slightly exothermic, the temperature of the kettle was controlled at 25°C, and the reaction was carried out for 7 hours . After the reaction was completed, the normalized content of 2-chloro-3-bromomethyl-4-methanesulfonylbenzoic acid sodium salt in liquid chromatography was 97.8%, and the solvent was removed under negative pressure and used directly for the subsequent etherific...

Embodiment 3

[0081] (1) The preparation of 2-chloro-3-bromomethyl-4-methanesulfonyl benzoate, main reaction process can be expressed with following reaction equation:

[0082]

[0083] Add 70 mL of tert-butanol into the reaction bottle, start stirring, drop 14 g of sodium hydroxide (30%, 0.105 mol) into it at room temperature, after the sodium hydroxide is uniformly dispersed, control the temperature of the kettle at 30 ° C, and add 34.8 g of 2 -Chloro-3-bromomethyl-4-methylsulfonylbenzoic acid methyl ester (98%, 0.1mol) was poured into the kettle for alkaline hydrolysis reaction, the reaction process was slightly exothermic, the temperature of the kettle was controlled at 30°C, and the reaction was carried out for 12 hours. After the reaction was completed, the normalized content of 2-chloro-3-bromomethyl-4-methanesulfonylbenzoic acid sodium salt in liquid chromatography was 92.5%, and the solvent was removed under negative pressure and used directly for the subsequent etherification re...

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