2,3,5,6-Tetrafluoroterephthalonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 g of ethylbenzene and 3.0 g of 5% palladium/activated carbon were added to a 1000 cc stainless steel autoclave. The gas phase was sufficiently replaced with hydrogen gas, then hydrogen gas was used to apply a pressure of 0.3 MPa and make the temperature 100° C. and catalytic pretreatment was carried out for 1 hour. The gas phase was again sufficiently replaced with nitrogen, then 3.0 g of the reaction material, that is, 2,3,5,6-tetrafluoroterephthalonitrile was added. The nitrogen atmosphere was maintained, the autoclave sealed as it was at atmospheric pressure, and the temperature held at 175° C. After 3 hours, the reaction solution was analyzed by gas chromatography, whereupon the conversion of 2,3,5,6-tetrafluoroterephthalonitrile was found to be 100% and the yield of 2,3,5,6-tetrafluorobenzonitrile (based on 2,3,5,6-tetrafluoroterephthalonitrile) was 95%. At the same time, 13.4 mmol of α-methylbenzylcyanide was produced. This corresponded to 0.95 times molar amount relative to the production of 2,3,5,6-tetrafluorobenzonitrile. the temperature 100° C. and catalytic pretreatment The nitrogen atmosphere was maintained the autoclave sealed as it held at 175° C After 3 hours

Conditions: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 g of ethylbenzene, 0.30 g of 5% palladium/activated carbon, and 6.0 g of 2,3,5,6-tetrafluoroterephthalonitrile were added to a 1000 cc stainless steel autoclave in a nitrogen atmosphere. The gas phase was sufficiently replaced with a mixed gas of 41 vol % hydrogen and 59 vol % nitrogen, then the mixed gas was used to keep the pressure at 0.23 MPa and the temperature was maintained at 190° C. After 2, 4, and 6 hours, the reaction solution was analyzed by gas chromatography, whereupon the conversions of 2,3,5,6-tetrafluoroterephthalonitrile were found to be 23, 62, and 99% and the yields of 2,3,5,6-tetrafluorobenzonitrile (based on 2,3,5,6-tetrafluoroterephthalonitrile) were 22, 56, and 87%, respectively. After 2, 4, and 6 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of N,N-diisopropylethylamine (19.2 g, 110 mmol) in CH3CN (100 mL) was added acetone oxime (8 g, 110 mmol). After stirring for 30 min, a solution of tetrafluoroterephthalonitrile (20 g, 100 mmol) in CH3CN (50 mL) was added; and the mixture was stirred overnight. Saturated aqueous ammonium chloride (100 mL) was added and the solvents were removed in vacuo. The residue was partitioned between EtOAc and brine. The layers were separated and the organic phase was washed once with brine, dried (MgSO4), filtered and concentrated. This crude solid was suspended in EtOH (150 mL) and concentrated HCl (50 mL) and water (100 mL) were added. This was refluxed for 3 h. After cooling to room temperature, the solvents were removed in vacuo. The residue was treated with saturated aqueous sodium bicarbonate (200 mL), and the product was extracted by washing the aqueous layer three times with EtOAc. This organic solution was washed once with brine, dried (MgSO4), filtered and concentrated to give a yellow solid. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes to 40% EtOAc/hexanes (9.2 g, 43%). and the mixture was stirred overnight the solvents were removed in vacuo The residue was partitioned between EtOAc and brine The layers were separated the organic phase was washed once with brine dried (MgSO4) filtered concentrated concentrated HCl (50 mL) and water (100 mL) were added This was refluxed for 3 h the solvents were removed in vacuo The residue was treated with saturated aqueous sodium bicarbonate (200 mL) the product was extracted by washing the aqueous layer three times with EtOAc This organic solution was washed once with brine dried (MgSO4) filtered concentrated to give a yellow solid The crude product was purified by silica gel chromatography eluting with a gradient of hexanes to 40% EtOAc/hexanes (9.2 g, 43%)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of N-(β-hydroxyethyl)diethylamine (5.86 g) and 2,4-diaminobenzene sulphonic acid (7.52 g) in dimethylsulphoxide (45 cm3) was added 1,2,4,5-tetrafluoro-3,6-dicyanobenzene (8.25 g) portionwise with stirring. The mixture was heated at 75° C. for 4 hours then poured into ice/water (140 cm3) to give a solution of 2-amino-4-(2,4,5-trifluoro-3,6-dicyanophenylamino)benzene sulphonic acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of N,N-diisopropylethylamine (19.2 g, 110 mmol) in CH3CN (100 mL) was added acetone oxime (8 g, 110 mmol). After stirring for 30 min, a solution of tetrafluoroterephthalonitrile (20 g, 100 mmol) in CH3CN (50 mL) was added; and the mixture was stirred overnight. Saturated aqueous ammonium chloride (100 mL) was added and the solvents were removed in vacuo. The residue was partitioned between EtOAc and brine. The layers were separated and the organic phase was washed once with brine, dried (MgSO4), filtered and concentrated. This crude solid was suspended in EtOH (150 mL) and concentrated HCl (50 mL) and water (100 mL) were added. This was refluxed for 3 h. After cooling to room temperature, the solvents were removed in vacuo. The residue was treated with saturated aqueous sodium bicarbonate (200 mL), and the product was extracted by washing the aqueous layer three times with EtOAc. This organic solution was washed once with brine, dried (MgSO4), filtered and concentrated to give a yellow solid. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes to 40% EtOAc/hexanes (9.2 g, 43%). and the mixture was stirred overnight the solvents were removed in vacuo The residue was partitioned between EtOAc and brine The layers were separated the organic phase was washed once with brine dried (MgSO4) filtered concentrated concentrated HCl (50 mL) and water (100 mL) were added This was refluxed for 3 h the solvents were removed in vacuo The residue was treated with saturated aqueous sodium bicarbonate (200 mL) the product was extracted by washing the aqueous layer three times with EtOAc This organic solution was washed once with brine dried (MgSO4) filtered concentrated to give a yellow solid The crude product was purified by silica gel chromatography eluting with a gradient of hexanes to 40% EtOAc/hexanes (9.2 g, 43%)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,3,5,6-tetrafluoroterephthalonitrile (1 g, 5 mmol) was dissolved in acetone (15 mL) in a 2-necked flask under Nitrogen. A solution of tert-butyl piperazine-1-carboxylate (1.39 g, 7.5 mmol) in water (3 mL) was then added followed by triethylamine (1.01 g, 10 mmol). The solution was heated to 55° C. for 8 h then cooled to rt. The resulting solid was filtered then washed with acetone. The filtrate was concentrated under vacuum and the residue was dissolved again in DCM (30 mL) and washed once with 1M HCl (30 mL) and once with brine (30 mL). The organics were dried over Na2SO4, filtered and the solvent removed in vacuo to give tert-butyl 4-(2,5-dicyano-3,4,6-trifluorophenyl)piperazine-1-carboxylate as a bright yellow solid (0.938 g, 51% yield). then cooled to rt The resulting solid was filtered then washed with acetone The filtrate was concentrated under vacuum the residue was dissolved again in DCM (30 mL) washed once with 1M HCl (30 mL) and once with brine (30 mL) The organics were dried over Na2SO4 filtered the solvent removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 g of ethylbenzene and 3.0 g of 5% palladium/activated carbon were added to a 1000 cc stainless steel autoclave. The gas phase was sufficiently replaced with hydrogen gas, then hydrogen gas was used to apply a pressure of 0.3 MPa and make the temperature 100° C. and catalytic pretreatment was carried out for 1 hour. The gas phase was again sufficiently replaced with nitrogen, then 3.0 g of the reaction material, that is, 2,3,5,6-tetrafluoroterephthalonitrile was added. The nitrogen atmosphere was maintained, the autoclave sealed as it was at atmospheric pressure, and the temperature held at 175° C. After 3 hours, the reaction solution was analyzed by gas chromatography, whereupon the conversion of 2,3,5,6-tetrafluoroterephthalonitrile was found to be 100% and the yield of 2,3,5,6-tetrafluorobenzonitrile (based on 2,3,5,6-tetrafluoroterephthalonitrile) was 95%. At the same time, 13.4 mmol of α-methylbenzylcyanide was produced. This corresponded to 0.95 times molar amount relative to the production of 2,3,5,6-tetrafluorobenzonitrile. the temperature 100° C. and catalytic pretreatment The nitrogen atmosphere was maintained the autoclave sealed as it held at 175° C After 3 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 g of ethylbenzene and 3.0 g of 5% palladium/activated carbon were added to a 1000 cc stainless steel autoclave. The gas phase was sufficiently replaced with hydrogen gas, then hydrogen gas was used to apply a pressure of 0.3 MPa and make the temperature 100° C. and catalytic pretreatment was carried out for 1 hour. The gas phase was again sufficiently replaced with nitrogen, then 3.0 g of the reaction material, that is, 2,3,5,6-tetrafluoroterephthalonitrile was added. The nitrogen atmosphere was maintained, the autoclave sealed as it was at atmospheric pressure, and the temperature held at 175° C. After 3 hours, the reaction solution was analyzed by gas chromatography, whereupon the conversion of 2,3,5,6-tetrafluoroterephthalonitrile was found to be 100% and the yield of 2,3,5,6-tetrafluorobenzonitrile (based on 2,3,5,6-tetrafluoroterephthalonitrile) was 95%. At the same time, 13.4 mmol of α-methylbenzylcyanide was produced. This corresponded to 0.95 times molar amount relative to the production of 2,3,5,6-tetrafluorobenzonitrile. the temperature 100° C. and catalytic pretreatment The nitrogen atmosphere was maintained the autoclave sealed as it held at 175° C After 3 hours

Conditions: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 g of ethylbenzene, 0.30 g of 5% palladium/activated carbon, and 6.0 g of 2,3,5,6-tetrafluoroterephthalonitrile were added to a 1000 cc stainless steel autoclave in a nitrogen atmosphere. The gas phase was sufficiently replaced with a mixed gas of 41 vol % hydrogen and 59 vol % nitrogen, then the mixed gas was used to keep the pressure at 0.23 MPa and the temperature was maintained at 190° C. After 2, 4, and 6 hours, the reaction solution was analyzed by gas chromatography, whereupon the conversions of 2,3,5,6-tetrafluoroterephthalonitrile were found to be 23, 62, and 99% and the yields of 2,3,5,6-tetrafluorobenzonitrile (based on 2,3,5,6-tetrafluoroterephthalonitrile) were 22, 56, and 87%, respectively. After 2, 4, and 6 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of N,N-diisopropylethylamine (19.2 g, 110 mmol) in CH3CN (100 mL) was added acetone oxime (8 g, 110 mmol). After stirring for 30 min, a solution of tetrafluoroterephthalonitrile (20 g, 100 mmol) in CH3CN (50 mL) was added; and the mixture was stirred overnight. Saturated aqueous ammonium chloride (100 mL) was added and the solvents were removed in vacuo. The residue was partitioned between EtOAc and brine. The layers were separated and the organic phase was washed once with brine, dried (MgSO4), filtered and concentrated. This crude solid was suspended in EtOH (150 mL) and concentrated HCl (50 mL) and water (100 mL) were added. This was refluxed for 3 h. After cooling to room temperature, the solvents were removed in vacuo. The residue was treated with saturated aqueous sodium bicarbonate (200 mL), and the product was extracted by washing the aqueous layer three times with EtOAc. This organic solution was washed once with brine, dried (MgSO4), filtered and concentrated to give a yellow solid. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes to 40% EtOAc/hexanes (9.2 g, 43%). and the mixture was stirred overnight the solvents were removed in vacuo The residue was partitioned between EtOAc and brine The layers were separated the organic phase was washed once with brine dried (MgSO4) filtered concentrated concentrated HCl (50 mL) and water (100 mL) were added This was refluxed for 3 h the solvents were removed in vacuo The residue was treated with saturated aqueous sodium bicarbonate (200 mL) the product was extracted by washing the aqueous layer three times with EtOAc This organic solution was washed once with brine dried (MgSO4) filtered concentrated to give a yellow solid The crude product was purified by silica gel chromatography eluting with a gradient of hexanes to 40% EtOAc/hexanes (9.2 g, 43%)