Synthesis method of 2-amino-3, 5-dichloro-N-methylbenzamide

Abstract

The invention relates to a synthesis method of 2-amino-3, 5-dichloro-N-methylbenzamide, which comprises the following steps: 1) adding isatoic anhydride into a solvent A, dropwisely adding a methylamine solution to react, adding water, uniformly stirring, standing for layering, and extracting an organic phase; and 2) slowly adding trichloroisocyanuric acid into the organic phase extracted in the step 1) for reaction, after the reaction is finished, removing the solvent A, adding water, adjusting the pH value to 8-13, performing suction filtration to obtain a white solid, and pulping the whitesolid by using the solvent B to obtain the 2-amino-3, 5-dichloro-N-methylbenzamide. The trichloroisocyanuric acid adopted in the method is high in reaction activity, a product obtained after chlorination reaction forms soluble salt under the alkaline condition, the soluble salt can be dissolved in water and can be well separated, the whole production process is low in cost, the reaction process issimple, production is easy, the yield is high, the finished product purity is high, the total income is high, and environmental pollution is small. Important reference can be provided for industrialproduction.

Description

technical field

[0001] The invention relates to the field of medicinal chemistry, in particular to a synthesis method of 2-amino-3,5-dichloro-N-methylbenzamide. Background technique

[0002] The intermediate 2-amino-3,5-dichloro-N-methylbenzamide is an important pesticide intermediate used in the synthesis of the bisamide pesticide tetrachlorantraniliprole. Chlorantraniliprole has comparable activity to chlorantraniliprole. However, the intermediate 2-amino-5-chloro-N,3-dimethylbenzamide used by chlorantraniliprole has many synthetic steps and high cost. Patent CN101298451B discloses a 2-amino-3,5-dichloro -N-Methylbenzamide. The starting raw material 2-amino-N-methylbenzamide is relatively expensive, and the cost of N-chlorosuccinimide is relatively high, resulting in a large amount of solid waste.

[0003] It is of great significance to study an intermediate 2-amino-3,5-dichloro-N-methylbenzamide which is simple and practical, has high economical efficiency, less side ...

Examples

preparation example Construction

[0035] The invention discloses a synthesis method of 2-amino-3,5-dichloro-N-methylbenzamide. The synthesis method is a one-pot method, comprising the following steps:

[0036] 1) Add isatoic anhydride to solvent A, add methylamine solution dropwise to react, the reaction temperature can be controlled at about 10°C to 50°C, and the effect is best when the temperature is 30°C. After the reaction, add water and stir evenly Set the layers, extract the organic phase, the organic phase is 2-amino-N-methylbenzamide;

[0037] 2) Slowly add trichloroisocyanuric acid to the organic phase extracted in step 1) for reaction. The reaction temperature can be controlled at about 30°C-80°C, and the effect is best when the temperature is 40°C-50°C. After the reaction, Remove the solvent, add water, and adjust the pH to 8-13. You can use sodium hydroxide, sodium carbonate and other reagents to adjust the pH value. After adjusting the pH, perform suction filtration. After suction filtration, a wh...

Embodiment 1

[0048] At room temperature, in a 500ml round bottom flask, add 50g of isatoic anhydride and 250ml of ethyl acetate, control the reaction temperature not to exceed 30°C, add 37.3g of 25% methylamine solution dropwise, after the dropwise addition, keep warm at 30°C for reaction After 4 hours, the reaction was monitored by liquid chromatography, and isatoic anhydride disappeared. Add 100ml of water, stir evenly, and let stand to separate layers. The upper layer is an ethyl acetate organic phase, and the lower layer is an aqueous phase. The liquid was separated and the aqueous phase was discarded.

[0049] Add 51.3g of trichloroisocyanuric acid directly to the organic phase in batches, and control the temperature not to exceed 40°C when feeding. After feeding, keep warm at 50°C for reaction, and use HPLC to monitor the product 2-amino-N-formazan in the previous step. After methyl benzamide and monochlorinated 2-amino-N-methylbenzamide disappear, add 10g of sodium sulfite to quen...

Embodiment 2

[0052] At room temperature, in a 500ml round bottom flask, add 50g of isatoic anhydride and 300ml of isopropyl acetate, control the reaction temperature not to exceed 30°C, add 37.3g of 25% methylamine aqueous solution dropwise, after the dropwise addition, keep warm at 30°C After 4 hours of reaction, the reaction was monitored by liquid chromatography, and isatoic anhydride disappeared. Add 100ml of water, stir evenly, and let stand to separate layers. The upper layer is the organic phase of isopropyl acetate, and the lower layer is the water phase, and the liquid is separated, and the water phase is discarded.

[0053] Add 51.3g of trichloroisocyanuric acid directly to the organic phase in batches, and control the temperature not to exceed 40°C when feeding. After feeding, keep warm at 50°C for reaction, and use HPLC to monitor the product 2-amino-N-formazan in the previous step. After the disappearance of phenylbenzamide and monochlorinated 2-amino-N-methylbenzamide. Add ...

technical field

[0001] The invention relates to the field of medicinal chemistry, in particular to a synthesis method of 2-amino-3,5-dichloro-N-methylbenzamide. Background technique

[0002] The intermediate 2-amino-3,5-dichloro-N-methylbenzamide is an important pesticide intermediate used in the synthesis of the bisamide pesticide tetrachlorantraniliprole. Chlorantraniliprole has comparable activity to chlorantraniliprole. However, the intermediate 2-amino-5-chloro-N,3-dimethylbenzamide used by chlorantraniliprole has many synthetic steps and high cost. Patent CN101298451B discloses a 2-amino-3,5-dichloro -N-Methylbenzamide. The starting raw material 2-amino-N-methylbenzamide is relatively expensive, and the cost of N-chlorosuccinimide is relatively high, resulting in a large amount of solid waste.

[0003] It is of great significance to study an intermediate 2-amino-3,5-dichloro-N-methylbenzamide which is simple and practical, has high economical efficiency, less side ...

Examples

preparation example Construction

[0035] The invention discloses a synthesis method of 2-amino-3,5-dichloro-N-methylbenzamide. The synthesis method is a one-pot method, comprising the following steps:

[0036] 1) Add isatoic anhydride to solvent A, add methylamine solution dropwise to react, the reaction temperature can be controlled at about 10°C to 50°C, and the effect is best when the temperature is 30°C. After the reaction, add water and stir evenly Set the layers, extract the organic phase, the organic phase is 2-amino-N-methylbenzamide;

[0037] 2) Slowly add trichloroisocyanuric acid to the organic phase extracted in step 1) for reaction. The reaction temperature can be controlled at about 30°C-80°C, and the effect is best when the temperature is 40°C-50°C. After the reaction, Remove the solvent, add water, and adjust the pH to 8-13. You can use sodium hydroxide, sodium carbonate and other reagents to adjust the pH value. After adjusting the pH, perform suction filtration. After suction filtration, a wh...

Embodiment 1

[0048] At room temperature, in a 500ml round bottom flask, add 50g of isatoic anhydride and 250ml of ethyl acetate, control the reaction temperature not to exceed 30°C, add 37.3g of 25% methylamine solution dropwise, after the dropwise addition, keep warm at 30°C for reaction After 4 hours, the reaction was monitored by liquid chromatography, and isatoic anhydride disappeared. Add 100ml of water, stir evenly, and let stand to separate layers. The upper layer is an ethyl acetate organic phase, and the lower layer is an aqueous phase. The liquid was separated and the aqueous phase was discarded.

[0049] Add 51.3g of trichloroisocyanuric acid directly to the organic phase in batches, and control the temperature not to exceed 40°C when feeding. After feeding, keep warm at 50°C for reaction, and use HPLC to monitor the product 2-amino-N-formazan in the previous step. After methyl benzamide and monochlorinated 2-amino-N-methylbenzamide disappear, add 10g of sodium sulfite to quen...

Embodiment 2

[0052] At room temperature, in a 500ml round bottom flask, add 50g of isatoic anhydride and 300ml of isopropyl acetate, control the reaction temperature not to exceed 30°C, add 37.3g of 25% methylamine aqueous solution dropwise, after the dropwise addition, keep warm at 30°C After 4 hours of reaction, the reaction was monitored by liquid chromatography, and isatoic anhydride disappeared. Add 100ml of water, stir evenly, and let stand to separate layers. The upper layer is the organic phase of isopropyl acetate, and the lower layer is the water phase, and the liquid is separated, and the water phase is discarded.

[0053] Add 51.3g of trichloroisocyanuric acid directly to the organic phase in batches, and control the temperature not to exceed 40°C when feeding. After feeding, keep warm at 50°C for reaction, and use HPLC to monitor the product 2-amino-N-formazan in the previous step. After the disappearance of phenylbenzamide and monochlorinated 2-amino-N-methylbenzamide. Add ...

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