Synthesis method for intermediate 1-(3-chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid

Abstract

Relating to the organic synthesis field, the invention in particular discloses a synthesis method for an intermediate 1-(3-chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid. The synthesis method includes the steps of: taking 3-aminocrotononitrile as the raw material, mixing the raw material with hydrazine hydrate, carrying out cyclization reaction, bromination reaction, oxidation reaction and condensation reaction in order to obtain 1-(3-chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid. The synthesis method provided by the invention provides a path for synthesis of the intermediate 1-(3-chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid, the reaction conditions of each step are mild, good yield can be achieved, and the production cost is reduced.

Description

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a method for synthesizing an intermediate 1-(3-chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid. Background technique

[0002] Chlorantraniliprole is the first broad-spectrum insecticide with a novel o-amidobenzamide chemical structure discovered and developed by DuPont. Chlorantraniliprole’s ISO generic name is Chlorantraniliprole, and its chemical name is 3-bromo-N-{4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl}-1-(3-chloro -2-pyridyl)-1H-pyrazole-5-amide, CAS Registry No. 500008-45-7. Its chemical structural formula is as shown in formula I:

[0003] (Formula I)

[0004] 1-(3-Chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid is an important intermediate in the synthesis of chlorantraniliprole

[0005]

[0006] There are two main synthetic methods of the existing intermediate 1-(3-chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid.

[0007] The first ...

Examples

Embodiment 1

[0034] S1. Dissolve 2.46g of 3-aminocrotononitrile (1) and 20mL of water with a mass fraction of 25% hydrazine hydrate in a 50mL three-necked flask; heat at 80°C to reflux for 8 hours; after the reaction, the excess hydrazine hydrate is vacuum pumped dry; the residue was distilled to obtain 3-amino-5-methylpyrazole (2), with a yield of 75%;

[0035] S2. Mix 1.9g 3-amino-5-methylpyrazole (2), 15mL concentrated hydrobromic acid, and 2.8g cuprous bromide in a 100mL three-neck flask, heat to 70°C; take about 1.5g nitrous acid Sodium was dissolved in 5mL of water, and slowly added dropwise into a three-neck flask using a constant pressure funnel; after the addition was complete, the reaction solution was stirred at 70°C for 30min, then cooled to room temperature, and 20mL of THF and 20mL of water were added; extracted three times with 30mL of ether, and the organic layer was After washing with sodium thiosulfate solution, dry with magnesium sulfate; then filter with silica gel, and...

Embodiment 2

[0039] S1. Dissolve 2.46g of 3-aminocrotononitrile (1) and 15mL of 40% hydrazine hydrate in water into a 50mL three-necked flask; heat to reflux at 60°C for 24 hours; pump excess hydrazine hydrate under vacuum after the reaction dry; the residue was distilled to obtain 3-amino-5-methylpyrazole (2), with a yield of 67%;

[0040] S2. Mix 1.9g 3-amino-5-methylpyrazole (2), 10mL concentrated hydrobromic acid, and 2.0g cuprous bromide in a 100mL three-necked flask, heat to 40°C; take about 1.0g nitrous acid Sodium was dissolved in 5mL of water, and slowly added dropwise into a three-neck flask using a constant pressure funnel; after the addition was complete, the reaction solution was stirred at 60°C for 40min, then cooled to room temperature, and 20mL of THF and 20mL of water were added; extracted three times with 30mL of ether, and the organic layer was After washing with sodium thiosulfate solution, dry with magnesium sulfate; then filter with silica gel, and distill off the sol...

Embodiment 3

[0044] S1. Dissolve 2.46g of 3-aminocrotononitrile (1) and 24mL of 20% hydrazine hydrate in water into a 50mL three-neck flask; heat to reflux at 80°C for 8 hours; after the reaction, the excess hydrazine hydrate is vacuum pumped dry; the residue was distilled to obtain 3-amino-5-methylpyrazole (2), with a yield of 68%;

[0045] S2. Mix 1.9g 3-amino-5-methylpyrazole (2), 18mL concentrated hydrobromic acid, and 3.5g cuprous bromide in a 100mL three-necked flask, heat to 60°C; take about 1.8g nitrous acid Sodium was dissolved in 5mL of water, and slowly added dropwise into a three-neck flask using a constant pressure funnel; after the addition was complete, the reaction solution was stirred at 80°C for 20 minutes, then cooled to room temperature, and 20mL of THF and 20mL of water were added; extracted three times with 30mL of ether, and the organic layer was After washing with sodium thiosulfate solution, dry with magnesium sulfate; then filter with silica gel, and distill off t...

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a method for synthesizing an intermediate 1-(3-chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid. Background technique

[0002] Chlorantraniliprole is the first broad-spectrum insecticide with a novel o-amidobenzamide chemical structure discovered and developed by DuPont. Chlorantraniliprole’s ISO generic name is Chlorantraniliprole, and its chemical name is 3-bromo-N-{4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl}-1-(3-chloro -2-pyridyl)-1H-pyrazole-5-amide, CAS Registry No. 500008-45-7. Its chemical structural formula is as shown in formula I:

[0003] (Formula I)

[0004] 1-(3-Chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid is an important intermediate in the synthesis of chlorantraniliprole

[0005]

[0006] There are two main synthetic methods of the existing intermediate 1-(3-chloro-2-pyridyl)-3-bromo-1H-5-pyrazolecarboxylic acid.

[0007] The first ...

Examples

Embodiment 1

[0034] S1. Dissolve 2.46g of 3-aminocrotononitrile (1) and 20mL of water with a mass fraction of 25% hydrazine hydrate in a 50mL three-necked flask; heat at 80°C to reflux for 8 hours; after the reaction, the excess hydrazine hydrate is vacuum pumped dry; the residue was distilled to obtain 3-amino-5-methylpyrazole (2), with a yield of 75%;

[0035] S2. Mix 1.9g 3-amino-5-methylpyrazole (2), 15mL concentrated hydrobromic acid, and 2.8g cuprous bromide in a 100mL three-neck flask, heat to 70°C; take about 1.5g nitrous acid Sodium was dissolved in 5mL of water, and slowly added dropwise into a three-neck flask using a constant pressure funnel; after the addition was complete, the reaction solution was stirred at 70°C for 30min, then cooled to room temperature, and 20mL of THF and 20mL of water were added; extracted three times with 30mL of ether, and the organic layer was After washing with sodium thiosulfate solution, dry with magnesium sulfate; then filter with silica gel, and...

Embodiment 2

[0039] S1. Dissolve 2.46g of 3-aminocrotononitrile (1) and 15mL of 40% hydrazine hydrate in water into a 50mL three-necked flask; heat to reflux at 60°C for 24 hours; pump excess hydrazine hydrate under vacuum after the reaction dry; the residue was distilled to obtain 3-amino-5-methylpyrazole (2), with a yield of 67%;

[0040] S2. Mix 1.9g 3-amino-5-methylpyrazole (2), 10mL concentrated hydrobromic acid, and 2.0g cuprous bromide in a 100mL three-necked flask, heat to 40°C; take about 1.0g nitrous acid Sodium was dissolved in 5mL of water, and slowly added dropwise into a three-neck flask using a constant pressure funnel; after the addition was complete, the reaction solution was stirred at 60°C for 40min, then cooled to room temperature, and 20mL of THF and 20mL of water were added; extracted three times with 30mL of ether, and the organic layer was After washing with sodium thiosulfate solution, dry with magnesium sulfate; then filter with silica gel, and distill off the sol...

Embodiment 3

[0044] S1. Dissolve 2.46g of 3-aminocrotononitrile (1) and 24mL of 20% hydrazine hydrate in water into a 50mL three-neck flask; heat to reflux at 80°C for 8 hours; after the reaction, the excess hydrazine hydrate is vacuum pumped dry; the residue was distilled to obtain 3-amino-5-methylpyrazole (2), with a yield of 68%;

[0045] S2. Mix 1.9g 3-amino-5-methylpyrazole (2), 18mL concentrated hydrobromic acid, and 3.5g cuprous bromide in a 100mL three-necked flask, heat to 60°C; take about 1.8g nitrous acid Sodium was dissolved in 5mL of water, and slowly added dropwise into a three-neck flask using a constant pressure funnel; after the addition was complete, the reaction solution was stirred at 80°C for 20 minutes, then cooled to room temperature, and 20mL of THF and 20mL of water were added; extracted three times with 30mL of ether, and the organic layer was After washing with sodium thiosulfate solution, dry with magnesium sulfate; then filter with silica gel, and distill off t...

Images