Method for producing trifluoromethylthioalkyl compound

Abstract

A method for producing a trifluoromethylthioalkyl compound represented by the general formula (1), characterized in that, in the presence of a compound represented by the following general formula (2) and a fluorine compound, adding temperature and add thiophosgene with an addition time of 0.25 hours or more. In the general formula (1), R represents a C1-C10 alkyl group substituted or unsubstituted by R1, R1 represents a C1-C4 alkyl group, etc., R2 represents a hydrogen atom, a halogen atom, a C1-C4 alkyl group, etc. In the general formula (2), R is as defined in the above-mentioned general formula (1), and L represents a halogen atom, a C1-C4 alkylsulfonyloxy group, or the like.

Description

technical field

[0001] The present invention relates to a method for producing a trifluoromethylthioalkyl compound, and particularly to a method for producing a trifluoromethylthioalkyl compound using a low-reactivity alkyl compound as a raw material. Background technique

[0002] Fluoroalkylthio groups are useful substituents in pharmaceutical and pesticide compounds. For example, the pest control agent disclosed in Patent Document 1 has a trifluoroethylsulfinyl group on the benzene ring and a trifluoromethylthio group at the end of the alkoxy side chain, and the fluoroalkylthio group has a significant role in pest control activity. play an important role in the expression.

[0003] In the method for producing a trifluoromethylthio group at the end of an alkoxy side chain described in Patent Document 1, first, a halogenated alkyl compound as a raw material is reacted with a metal thiocyanate to synthesize a thiocyanate compound ( "Manufacturing Method 11" of Patent Docume...

Examples

Embodiment 1

[0184] Production of 6-(trifluoromethylthio)hexyl acetate

[0185] [chemical 5]

[0186]

[0187] Add 7.2 mL (94 mmol) of thiophosgene dropwise to 400 mL of acetonitrile containing 15.0 g (67.2 mmol) of 6-bromohexyl acetate and 23.4 g (403 mmol) of potassium fluoride over a period of 1 hour using a dropping funnel solution (the temperature in the reaction system at this time was 80° C.). After stirring the reaction mixture under reflux for 1 hour, the reaction mixture was naturally cooled to room temperature, and the insoluble matter was filtered off. Water was added to the filtrate, followed by extraction with diisopropyl ether, and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine. The organic layer obtained by liquid separation was dried over anhydrous magnesium sulfate, and inorganic substances were filtered off, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by vacuum distill...

Embodiment 2～4

[0191] Change the addition temperature and addition time respectively, dropwise add thiophosgene 0.60mL (7.7mmol) acetonitrile 4.5mL solution to 6-bromohexyl acetate 1.2g (5.5mmol), potassium fluoride 1.9g (33mmol) acetonitrile 32mL solution. After stirring for 1 hour, a part of the reaction mixture was analyzed by GC, and the yield of the target product was calculated by the area percentage method. The results are summarized in Table 1 in the same manner as in Example 1. In addition, in the GC analysis of Examples 2-4, the unreacted raw material compound (6-bromohexyl acetate) was detected other than the object.

[0192] [Table 1]

[0193]

Embodiment 5

[0195] Production of ethyl 6-(trifluoromethylthio)hexanoate

[0196] [chemical 6]

[0197]

[0198] Add 1.2 mL (15 mmol) of thiophosgene in 3.8 mL of acetonitrile dropwise to 62 mL of acetonitrile containing 2.4 g (11 mmol) of ethyl 6-bromohexanoate and 3.8 g (65 mmol) of potassium fluoride over 1 hour under heating to reflux solution (the temperature in the reaction system at this time was 80° C.). The reaction mixture was stirred under reflux for 1 hour, and then cooled to room temperature naturally. Water was added to the reaction mixture, followed by extraction with diisopropyl ether, and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine. After the organic layer obtained by liquid separation was dried over anhydrous magnesium sulfate, the inorganic matter was filtered off, and the solvent was distilled off under reduced pressure to obtain 2.5 g of ethyl 6-(trifluoromethylthio)hexanoate as a reddish-brown liquid ( Yield 96%). ...

technical field

[0001] The present invention relates to a method for producing a trifluoromethylthioalkyl compound, and particularly to a method for producing a trifluoromethylthioalkyl compound using a low-reactivity alkyl compound as a raw material. Background technique

[0002] Fluoroalkylthio groups are useful substituents in pharmaceutical and pesticide compounds. For example, the pest control agent disclosed in Patent Document 1 has a trifluoroethylsulfinyl group on the benzene ring and a trifluoromethylthio group at the end of the alkoxy side chain, and the fluoroalkylthio group has a significant role in pest control activity. play an important role in the expression.

[0003] In the method for producing a trifluoromethylthio group at the end of an alkoxy side chain described in Patent Document 1, first, a halogenated alkyl compound as a raw material is reacted with a metal thiocyanate to synthesize a thiocyanate compound ( "Manufacturing Method 11" of Patent Docume...

Examples

Embodiment 1

[0184] Production of 6-(trifluoromethylthio)hexyl acetate

[0185] [chemical 5]

[0186]

[0187] Add 7.2 mL (94 mmol) of thiophosgene dropwise to 400 mL of acetonitrile containing 15.0 g (67.2 mmol) of 6-bromohexyl acetate and 23.4 g (403 mmol) of potassium fluoride over a period of 1 hour using a dropping funnel solution (the temperature in the reaction system at this time was 80° C.). After stirring the reaction mixture under reflux for 1 hour, the reaction mixture was naturally cooled to room temperature, and the insoluble matter was filtered off. Water was added to the filtrate, followed by extraction with diisopropyl ether, and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine. The organic layer obtained by liquid separation was dried over anhydrous magnesium sulfate, and inorganic substances were filtered off, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by vacuum distill...

Embodiment 2～4

[0191] Change the addition temperature and addition time respectively, dropwise add thiophosgene 0.60mL (7.7mmol) acetonitrile 4.5mL solution to 6-bromohexyl acetate 1.2g (5.5mmol), potassium fluoride 1.9g (33mmol) acetonitrile 32mL solution. After stirring for 1 hour, a part of the reaction mixture was analyzed by GC, and the yield of the target product was calculated by the area percentage method. The results are summarized in Table 1 in the same manner as in Example 1. In addition, in the GC analysis of Examples 2-4, the unreacted raw material compound (6-bromohexyl acetate) was detected other than the object.

[0192] [Table 1]

[0193]

Embodiment 5

[0195] Production of ethyl 6-(trifluoromethylthio)hexanoate

[0196] [chemical 6]

[0197]

[0198] Add 1.2 mL (15 mmol) of thiophosgene in 3.8 mL of acetonitrile dropwise to 62 mL of acetonitrile containing 2.4 g (11 mmol) of ethyl 6-bromohexanoate and 3.8 g (65 mmol) of potassium fluoride over 1 hour under heating to reflux solution (the temperature in the reaction system at this time was 80° C.). The reaction mixture was stirred under reflux for 1 hour, and then cooled to room temperature naturally. Water was added to the reaction mixture, followed by extraction with diisopropyl ether, and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine. After the organic layer obtained by liquid separation was dried over anhydrous magnesium sulfate, the inorganic matter was filtered off, and the solvent was distilled off under reduced pressure to obtain 2.5 g of ethyl 6-(trifluoromethylthio)hexanoate as a reddish-brown liquid ( Yield 96%). ...

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