Synthesis method of 2-chloro-3-fluoro-4-trifluoromethyl benzoyl chloride

Abstract

The invention discloses a synthesis method of 2-chloro-3-fluoro-4-trifluoromethyl benzoyl chloride, wherein the synthesis method comprises the steps: dissolving 2,3-dichlorobenzotrifluoride and potassium fluoride in a first solvent, and adding a first catalyst to obtain 2-fluoro-3-chlorobenzotrifluoride; dissolving an organic lithium reagent in a second solvent, reducing the temperature to -70 DEG C to -80 DEG C, adding 2-fluoro-3-chlorobenzotrifluoride, adding an acylation reagent, and thus obtaining 2-chloro-3-fluoro-4-trifluoromethyl benzaldehyde; and dissolving the 2-chloro-3-fluoro-4-trifluoromethyl benzaldehyde in a third solvent, and adding a chlorination reagent to obtain the 2-chloro-3-fluoro-4-trifluoromethyl benzoyl chloride. According to the invention, the 2-chloro-3-fluoro-4-trifluoromethyl benzoyl chloride is synthesized through a simple reaction, and flammable, explosive, highly toxic or difficult-to-store reagents commonly used in an existing synthesis method are not used in each reaction step, so that the harm to the environment and operators is avoided; and meanwhile, the yield of the product reaches 85% or above, and the purity is 95% or above.

Description

technical field

[0001] The invention relates to the field of synthesis of organic chemical intermediates, in particular to a synthesis method of 2-chloro-3-fluoro-4-trifluoromethylbenzoyl chloride. Background technique

[0002] Organic compounds with 4-trifluoromethylbenzoyl structural fragments are prone to produce various pharmacological and physiological activities, so they are widely used in medicine, pesticides, synthetic dyes and other fields.

[0003] 2-Chloro-3-fluoro-4-trifluoromethylbenzoyl chloride is an important 4-trifluoromethylbenzoyl derivative. 2-Chloro-3-fluoro-4-trifluoromethylbenzoyl chloride can not only react with other intermediates through the acid chloride group, but also the halogen group on its benzene ring can undergo various chemical reactions with various active reagents reaction to prepare pharmaceutical and pesticide products, so it has broad prospects.

[0004] The synthesis of disclosed 2-chloro-3-fluoro-4-trifluoromethylbenzoyl chloride m...

Examples

Embodiment 1

[0030] a) Preparation of 2-fluoro-3-chlorobenzotrifluoride

[0031] Add 215g of 2,3-dichlorobenzotrifluoride, 73g of potassium fluoride, 7g of triphenylphosphine bromide and 430mL of 1,3-dimethylimidazolidinone into a 1000mL three-necked flask equipped with a rectification column, and stir to raise the temperature Reflux reaction. After 1 hour of reaction, 185 g of a colorless transparent liquid began to evaporate slowly, and the content of GC analysis was 93.9%. The collected crude product was purified by rectification to obtain 160 g of a colorless transparent liquid, namely 2-fluoro-3-chlorotrifluorotoluene. GC content 98.5%, yield 68.3%

[0032] The reaction residue was cooled and filtered with suction, and the filtrate was recovered by distillation under reduced pressure to obtain 410 mL of 1,3-dimethylimidazolidinone.

[0033] b) Preparation of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde

[0034] Under the protection of nitrogen, add 500mL of dry tetrahydrofuran ...

Embodiment 2

[0039] a) Preparation of 2-fluoro-3-chlorobenzotrifluoride

[0040] Add 215g of 2,3-dichlorobenzotrifluoride, 100g of potassium fluoride, 3g of triethylamine and 450mL of 1,3-dimethylimidazolidinone into a 1000mL three-necked flask equipped with a rectification column, stir and raise the temperature to reflux for reaction. After 4 hours of reaction, 189 g of a colorless transparent liquid began to slowly distill out, and the content of GC analysis was 95.2%. The collected crude product was purified by rectification to obtain 164 g of a colorless transparent liquid, namely 2-fluoro-3-chlorobenzotrifluoride. GC content 98.7%, yield 70%.

[0041] The reaction residue was cooled and filtered with suction, and the filtrate was recovered by distillation under reduced pressure to obtain 420 mL of 1,3-dimethylimidazolidinone.

[0042] b) Preparation of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde

[0043] Under the protection of nitrogen, add 500mL of dry tetrahydrofuran to a 2L...

Embodiment 3

[0049] a) Preparation of 2-fluoro-3-chlorobenzotrifluoride

[0050] Add 215g of 2,3-dichlorobenzotrifluoride, 80g of potassium fluoride, 7g of DBU and 430mL of 1,3-dimethylimidazolidinone into a 1000mL three-necked flask equipped with a rectification column, stir and raise the temperature to reflux for reaction. After 2 hours of reaction, 188 g of a colorless transparent liquid began to slowly evaporate, and the content of GC analysis was 93.2%. The collected crude product was purified by rectification to obtain 165 g of a colorless transparent liquid, namely 2-fluoro-3-chlorobenzotrifluoride. GC content 97.8%, yield 70.4%.

[0051] The reaction residue was cooled and filtered with suction, and the filtrate was recovered by distillation under reduced pressure to obtain 408 mL of 1,3-dimethylimidazolidinone.

[0052] b) Preparation of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde

[0053] Under nitrogen protection, add 500mL dry tetrahydrofuran to a 2L three-necked flask, ...

technical field

[0001] The invention relates to the field of synthesis of organic chemical intermediates, in particular to a synthesis method of 2-chloro-3-fluoro-4-trifluoromethylbenzoyl chloride. Background technique

[0002] Organic compounds with 4-trifluoromethylbenzoyl structural fragments are prone to produce various pharmacological and physiological activities, so they are widely used in medicine, pesticides, synthetic dyes and other fields.

[0003] 2-Chloro-3-fluoro-4-trifluoromethylbenzoyl chloride is an important 4-trifluoromethylbenzoyl derivative. 2-Chloro-3-fluoro-4-trifluoromethylbenzoyl chloride can not only react with other intermediates through the acid chloride group, but also the halogen group on its benzene ring can undergo various chemical reactions with various active reagents reaction to prepare pharmaceutical and pesticide products, so it has broad prospects.

[0004] The synthesis of disclosed 2-chloro-3-fluoro-4-trifluoromethylbenzoyl chloride m...

Examples

Embodiment 1

[0030] a) Preparation of 2-fluoro-3-chlorobenzotrifluoride

[0031] Add 215g of 2,3-dichlorobenzotrifluoride, 73g of potassium fluoride, 7g of triphenylphosphine bromide and 430mL of 1,3-dimethylimidazolidinone into a 1000mL three-necked flask equipped with a rectification column, and stir to raise the temperature Reflux reaction. After 1 hour of reaction, 185 g of a colorless transparent liquid began to evaporate slowly, and the content of GC analysis was 93.9%. The collected crude product was purified by rectification to obtain 160 g of a colorless transparent liquid, namely 2-fluoro-3-chlorotrifluorotoluene. GC content 98.5%, yield 68.3%

[0032] The reaction residue was cooled and filtered with suction, and the filtrate was recovered by distillation under reduced pressure to obtain 410 mL of 1,3-dimethylimidazolidinone.

[0033] b) Preparation of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde

[0034] Under the protection of nitrogen, add 500mL of dry tetrahydrofuran ...

Embodiment 2

[0039] a) Preparation of 2-fluoro-3-chlorobenzotrifluoride

[0040] Add 215g of 2,3-dichlorobenzotrifluoride, 100g of potassium fluoride, 3g of triethylamine and 450mL of 1,3-dimethylimidazolidinone into a 1000mL three-necked flask equipped with a rectification column, stir and raise the temperature to reflux for reaction. After 4 hours of reaction, 189 g of a colorless transparent liquid began to slowly distill out, and the content of GC analysis was 95.2%. The collected crude product was purified by rectification to obtain 164 g of a colorless transparent liquid, namely 2-fluoro-3-chlorobenzotrifluoride. GC content 98.7%, yield 70%.

[0041] The reaction residue was cooled and filtered with suction, and the filtrate was recovered by distillation under reduced pressure to obtain 420 mL of 1,3-dimethylimidazolidinone.

[0042] b) Preparation of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde

[0043] Under the protection of nitrogen, add 500mL of dry tetrahydrofuran to a 2L...

Embodiment 3

[0049] a) Preparation of 2-fluoro-3-chlorobenzotrifluoride

[0050] Add 215g of 2,3-dichlorobenzotrifluoride, 80g of potassium fluoride, 7g of DBU and 430mL of 1,3-dimethylimidazolidinone into a 1000mL three-necked flask equipped with a rectification column, stir and raise the temperature to reflux for reaction. After 2 hours of reaction, 188 g of a colorless transparent liquid began to slowly evaporate, and the content of GC analysis was 93.2%. The collected crude product was purified by rectification to obtain 165 g of a colorless transparent liquid, namely 2-fluoro-3-chlorobenzotrifluoride. GC content 97.8%, yield 70.4%.

[0051] The reaction residue was cooled and filtered with suction, and the filtrate was recovered by distillation under reduced pressure to obtain 408 mL of 1,3-dimethylimidazolidinone.

[0052] b) Preparation of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde

[0053] Under nitrogen protection, add 500mL dry tetrahydrofuran to a 2L three-necked flask, ...

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