Synthetic method of 1, 1-2 fluorine - 1, 3 - acetylene compounds

Abstract

The invention discloses a synthetic method of 1, 1-2 fluorine - 1, 3 - acetylene compounds. The synthetic method enable tosylhydrazones and acetylene compounds of Alpha, alpha, alpha, 3 methyl ketone to react in organic solvent. 1, 1-2 fluorine - 1, 3 - acetylene compounds is obtained through the catalysis of cuprous CuX and the existing of soda and annexing agent. The synthetic method of 1, 1-2 fluorine - 1, 3 - acetylene compounds preferentially uses copper iodide which is cheap and stable as catalyst, and the operation is relatively convenient and easy. Also the copper iodide has good tolerance and universality to functional groups. The invention has the advantages that the raw materials are easy to obtain, the reaction cost is relative low, and the reaction time is relative short. The invention is suitable for the preparation of 1, 1-2 fluorine - 1, 3 - acetylene compounds.

Description

technical field

[0001] The invention belongs to the field of organic synthesis, in particular to a synthesis method of 1,1-difluoro-1,3-enyne compound. Background technique

[0002] Due to its special chemical properties, fluorine atoms play an important role in the fields of material science, life science, and pharmaceuticals. Therefore, how to efficiently introduce fluorine-containing functional groups has become an important research direction for synthetic chemists. Among them, 1,1-difluoro-1,3-enyne compound is a special kind of enyne compound, which has a good application prospect. The traditional methods for synthesizing this kind of compounds are mainly: 1) using the building block containing difluoroalkene and alkyne for coupling synthesis, 2) using Wittig reaction. However, the practicability of these methods is low. Firstly, the synthesis of coupling blocks with difluoroolefins is a big problem, requiring relatively harsh conditions, and there is a big problem in...

Examples

Embodiment 1

[0048] 2,4-Diphenyl 1,1-difluoro-1-en-3-yne

[0049]Take a 10mL Schlenk tube, put it into a magnet stopper, put a rubber stopper on it, heat and dry it, and cool it under nitrogen, then add 68mg (0.2mmol ), lithium tert-butoxide 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), appropriate amount of additives, nitrogen pumping, then add 3mL 1,4-dioxane, add phenylacetylene 20mg (0.2 mmol). React at a certain temperature on an electromagnetic heating stirrer for about 2 hours. After the reaction, use a 10mL sand core column filled with 3cm high silica gel to filter and elute with an appropriate amount of petroleum ether. The resulting filtrate is removed from the reaction solvent by a rotary evaporator and purified by column chromatography to obtain 2,4-diphenyl 1,1-difluoro-1-en-3-yne, its structure is shown in the following formula:

[0050]

[0051] Taking this reaction as an example, under the condition that other conditions remain unchanged, by adjusting the type or rea...

Embodiment 2

[0057] 2-(4’-fluorophenyl)-4-phenyl 1,1-difluoro-1-en-3-yne

[0058] Take a 10mL Schlenk tube, put it into a magnetic sub-plug and put a rubber stopper on it, heat it to dry, cool it under nitrogen, then add 1,1,1-trifluoromethyl-2-(4'-fluorophenyl)ketone and p-toluenesulfonate Acylhydrazone 72mg (0.2mmol), lithium tert-butoxide 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), lithium trifluoromethanesulfonate 31mg (0.2mmol ), nitrogen pumped for ventilation, then 3mL of 1,4-dioxane was added, and 20mg (0.2mmol) of phenylacetylene was added under stirring. React on a 60° C. electromagnetic heating stirrer for about 2 hours. After the reaction, use a 10mL sand core column filled with 3cm high silica gel to filter and elute with an appropriate amount of petroleum ether. The resulting filtrate is removed from the reaction solvent using a rotary evaporator, and purified by column chromatography to obtain 2-(4'-fluoro Phenyl)-4-phenyl 1,...

Embodiment 3

[0062] 2-(4’-Chlorophenyl)-4-phenyl 1,1-difluoro-1-en-3-yne

[0063] Take a 10mL Schlenk tube, put it into a magnet stopper and put a rubber stopper on it, heat and dry, cool under nitrogen, then add 1,1,1-trifluoromethyl-2-(4'-chlorophenyl)ketone and p-toluenesulfonate Acylhydrazone 75mg (0.2mmol), lithium tert-butoxide 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), lithium trifluoromethanesulfonate 31mg (0.2mmol ), nitrogen pumped for ventilation, then 3mL of 1,4-dioxane was added, and 20mg (0.2mmol) of phenylacetylene was added under stirring. React on a 60° C. electromagnetic heating stirrer for about 2 hours. After the reaction is over, use a 10mL sand core column with 3cm high silica gel to filter and elute with an appropriate amount of petroleum ether. The resulting filtrate is removed from the reaction solvent using a rotary evaporator, and purified by column chromatography to obtain 2-(4'-chloro Phenyl)-4-phenyl 1,1-diflu...

technical field

[0001] The invention belongs to the field of organic synthesis, in particular to a synthesis method of 1,1-difluoro-1,3-enyne compound. Background technique

[0002] Due to its special chemical properties, fluorine atoms play an important role in the fields of material science, life science, and pharmaceuticals. Therefore, how to efficiently introduce fluorine-containing functional groups has become an important research direction for synthetic chemists. Among them, 1,1-difluoro-1,3-enyne compound is a special kind of enyne compound, which has a good application prospect. The traditional methods for synthesizing this kind of compounds are mainly: 1) using the building block containing difluoroalkene and alkyne for coupling synthesis, 2) using Wittig reaction. However, the practicability of these methods is low. Firstly, the synthesis of coupling blocks with difluoroolefins is a big problem, requiring relatively harsh conditions, and there is a big problem in...

Examples

Embodiment 1

[0048] 2,4-Diphenyl 1,1-difluoro-1-en-3-yne

[0049]Take a 10mL Schlenk tube, put it into a magnet stopper, put a rubber stopper on it, heat and dry it, and cool it under nitrogen, then add 68mg (0.2mmol ), lithium tert-butoxide 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), appropriate amount of additives, nitrogen pumping, then add 3mL 1,4-dioxane, add phenylacetylene 20mg (0.2 mmol). React at a certain temperature on an electromagnetic heating stirrer for about 2 hours. After the reaction, use a 10mL sand core column filled with 3cm high silica gel to filter and elute with an appropriate amount of petroleum ether. The resulting filtrate is removed from the reaction solvent by a rotary evaporator and purified by column chromatography to obtain 2,4-diphenyl 1,1-difluoro-1-en-3-yne, its structure is shown in the following formula:

[0050]

[0051] Taking this reaction as an example, under the condition that other conditions remain unchanged, by adjusting the type or rea...

Embodiment 2

[0057] 2-(4’-fluorophenyl)-4-phenyl 1,1-difluoro-1-en-3-yne

[0058] Take a 10mL Schlenk tube, put it into a magnetic sub-plug and put a rubber stopper on it, heat it to dry, cool it under nitrogen, then add 1,1,1-trifluoromethyl-2-(4'-fluorophenyl)ketone and p-toluenesulfonate Acylhydrazone 72mg (0.2mmol), lithium tert-butoxide 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), lithium trifluoromethanesulfonate 31mg (0.2mmol ), nitrogen pumped for ventilation, then 3mL of 1,4-dioxane was added, and 20mg (0.2mmol) of phenylacetylene was added under stirring. React on a 60° C. electromagnetic heating stirrer for about 2 hours. After the reaction, use a 10mL sand core column filled with 3cm high silica gel to filter and elute with an appropriate amount of petroleum ether. The resulting filtrate is removed from the reaction solvent using a rotary evaporator, and purified by column chromatography to obtain 2-(4'-fluoro Phenyl)-4-phenyl 1,...

Embodiment 3

[0062] 2-(4’-Chlorophenyl)-4-phenyl 1,1-difluoro-1-en-3-yne

[0063] Take a 10mL Schlenk tube, put it into a magnet stopper and put a rubber stopper on it, heat and dry, cool under nitrogen, then add 1,1,1-trifluoromethyl-2-(4'-chlorophenyl)ketone and p-toluenesulfonate Acylhydrazone 75mg (0.2mmol), lithium tert-butoxide 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), lithium trifluoromethanesulfonate 31mg (0.2mmol ), nitrogen pumped for ventilation, then 3mL of 1,4-dioxane was added, and 20mg (0.2mmol) of phenylacetylene was added under stirring. React on a 60° C. electromagnetic heating stirrer for about 2 hours. After the reaction is over, use a 10mL sand core column with 3cm high silica gel to filter and elute with an appropriate amount of petroleum ether. The resulting filtrate is removed from the reaction solvent using a rotary evaporator, and purified by column chromatography to obtain 2-(4'-chloro Phenyl)-4-phenyl 1,1-diflu...

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