1,2,4,5-tetrafluoro-3-methylbenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The product of step (a) above (4.3 g) was mixed with diethyl ether (30 ml), the mixture cooled to -70° C., and maintained at this temperature whilst a solution of n-butyllithium in n-hexane (1.6 M, 16.4 ml) was slowly added. The mixture was stirred for a period of 1 hour during which time a fine white precipitate was formed. Dry carbon dioxide gas was then passed into the mixture for 30 minutes whilst the temperature was maintained within the range -70° to -40° C., and continued to be passed in thereafter whilst the mixture was allowed to warm to the ambient temperature. After acidifying with dilute hydrochloric acid (6 N, 40 ml) the organic phase was separated, washed with water and dried over anhydrous magnesium sulphate. After evaporation of the solvents under reduced pressure the residual solid was recrystallised from toluene to yield 2,3,5,6-tetrafluoro-4-toluic acid, m.p. 170° C. identified by infra red and nuclear magnetic resonance spectroscopy. was slowly added was formed was maintained within the range -70° to -40° C. to warm to the ambient temperature was separated washed with water dried over anhydrous magnesium sulphate After evaporation of the solvents under reduced pressure the residual solid was recrystallised from toluene

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The product of step (a) above (4.3 g) was mixed with diethyl ether (30 ml), the mixture cooled to -70° C., and maintained at this temperature whilst a solution of n-butyllithium in n-hexane (1.6 M, 16.4 ml) was slowly added. The mixture was stirred for a period of 1 hour during which time a fine white precipitate was formed. Dry carbon dioxide gas was then passed into the mixture for 30 minutes whilst the temperature was maintained within the range -70° to -40° C., and continued to be passed in thereafter whilst the mixture was allowed to warm to the ambient temperature. After acidifying with dilute hydrochloric acid (6 N, 40 ml) the organic phase was separated, washed with water and dried over anhydrous magnesium sulphate. After evaporation of the solvents under reduced pressure the residual solid was recrystallised from toluene to yield 2,3,5,6-tetrafluoro-4-toluic acid, m.p. 170° C. identified by infra red and nuclear magnetic resonance spectroscopy. was slowly added was formed was maintained within the range -70° to -40° C. to warm to the ambient temperature was separated washed with water dried over anhydrous magnesium sulphate After evaporation of the solvents under reduced pressure the residual solid was recrystallised from toluene

反応条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of n-butyllithium in hexane (1.6 M, 62.5 ml) was added dropwise to a well stirred solution of 1,2,4,5-tetrafluorobenzene (15.0 g) in dry tetrahydrofuran (150 ml) maintained at a temperature of -60° C. under an atmosphere of dry argon. When the addition was complete the mixture was stirred at -45° C. for 2 hours and then methyl iodide (14.2 g) was added dropwise whilst the temperature was kept at -45° C. After a period of 30 minutes the mixture was allowed to warm to the ambient temperature, poured into distilled water and the mixture extracted with diethyl ether (2×50 ml), and the extracts dried over anhydrous magnesium sulphate. After filtering the solution was concentrated by evaporation of the solvents at atmospheric pressure. The residual oil was distilled and the fraction boiling in the range 115°-122° C. at atmospheric pressure (6.2 g) collected, identified by n.m.r. and gas chromatographic analysis as consisting of ca. 95% of the required 2,3,5,6-tetrafluorotoluene and ca. 5% of 2,3,5,6-tetrafluoro-1,4-xylene. When the addition was kept at -45° C After a period of 30 minutes the mixture was allowed to warm to the ambient temperature poured into distilled water the mixture extracted with diethyl ether (2×50 ml) the extracts dried over anhydrous magnesium sulphate After filtering the solution was concentrated by evaporation of the solvents at atmospheric pressure The residual oil was distilled boiling in the range 115°-122° C. at atmospheric pressure (6.2 g) collected

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of n-butyllithium (2.7M in n-hexane, 21 cm3) was added dropwise to a stirred solution of 2,3,5,6-tetrafluorotoluene (9.0 g) in dry dimethoxymethane cooled to -70° C. under a nitrogen atmosphere and the mixture stirred for one hour. Carbon dioxide was then passed into the mixture for 3 hours during which time a white solid precipitate formed. After allowing the mixture to attain the ambient temperature (ca. 22° C.) it was poured into water. The resultant mixture was acidified with dilute hydrochloric acid and extracted with diethyl ether. The ethereal extract was washed with water and dried over anhydrous magnesium sulphate. Removal of the solvent yielded a semi solid residue which on trituration with petroleum ether (boiling range 40°-60° C.) gave 4-methyl-2,3,5,6-tetrafluorobenzoic acid (2.5 g) white crystals, mp 168° C. (Infra red C=O, 1700 cm-1.) a white solid precipitate formed the ambient temperature (ca. 22° C.) it extracted with diethyl ether The ethereal extract was washed with water dried over anhydrous magnesium sulphate Removal of the solvent yielded a semi solid residue which on trituration with petroleum ether (boiling range 40°-60° C.)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2,3,5,6-tetrafluorotoluene (1.7 g), N-bromosuccinimide (1.9 g), dry carbon tetrachloride (10 ml) and benzoyl peroxide (0.01 g) was heated at the reflux temperature for 20 hours, cooled to the ambient temperature (ca. 25° C.) filtered and the filtrate diluted with diethyl ether. The ethereal solution was washed with water, dried over anhydrous magnesium sulphate and concentrated by evaporation of the solvents to yield 2,3,5,6-tetrafluorobenzyl bromide as a mobile colourlessoil. was heated at the reflux temperature for 20 hours filtered the filtrate diluted with diethyl ether The ethereal solution was washed with water dried over anhydrous magnesium sulphate concentrated by evaporation of the solvents

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2,3,5,6-tetrafluorotoluene (1.7 g), N-bromosuccinimide (1.9 g), dry carbon tetrachloride (10 ml) and benzoyl peroxide (0.01 g) was heated at the reflux temperature for 20 hours, cooled to the ambient temperature (ca.25° C.) filtered and the filtrate diluted with diethyl ether. The ethereal solution was washed with water, dried over anhydrous magnesium sulphate and concentrated by evaporation of the solvents to yield 2,3,5,6-tetrafluorobenzyl bromide as a mobile colourless oil. was heated at the reflux temperature for 20 hours filtered the filtrate diluted with diethyl ether The ethereal solution was washed with water dried over anhydrous magnesium sulphate concentrated by evaporation of the solvents

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The product of step (a) above (4.3 g) was mixed with diethyl ether (30 ml), the mixture cooled to -70° C., and maintained at this temperature whilst a solution of n-butyllithium in n-hexane (1.6 M, 16.4 ml) was slowly added. The mixture was stirred for a period of 1 hour during which time a fine white precipitate was formed. Dry carbon dioxide gas was then passed into the mixture for 30 minutes whilst the temperature was maintained within the range -70° to -40° C., and continued to be passed in thereafter whilst the mixture was allowed to warm to the ambient temperature. After acidifying with dilute hydrochloric acid (6 N, 40 ml) the organic phase was separated, washed with water and dried over anhydrous magnesium sulphate. After evaporation of the solvents under reduced pressure the residual solid was recrystallised from toluene to yield 2,3,5,6-tetrafluoro-4-toluic acid, m.p. 170° C. identified by infra red and nuclear magnetic resonance spectroscopy. was slowly added was formed was maintained within the range -70° to -40° C. to warm to the ambient temperature was separated washed with water dried over anhydrous magnesium sulphate After evaporation of the solvents under reduced pressure the residual solid was recrystallised from toluene

反応条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of n-butyllithium in hexane (1.6 M, 62.5 ml) was added dropwise to a well stirred solution of 1,2,4,5-tetrafluorobenzene (15.0 g) in dry tetrahydrofuran (150 ml) maintained at a temperature of -60° C. under an atmosphere of dry argon. When the addition was complete the mixture was stirred at -45° C. for 2 hours and then methyl iodide (14.2 g) was added dropwise whilst the temperature was kept at -45° C. After a period of 30 minutes the mixture was allowed to warm to the ambient temperature, poured into distilled water and the mixture extracted with diethyl ether (2×50 ml), and the extracts dried over anhydrous magnesium sulphate. After filtering the solution was concentrated by evaporation of the solvents at atmospheric pressure. The residual oil was distilled and the fraction boiling in the range 115°-122° C. at atmospheric pressure (6.2 g) collected, identified by n.m.r. and gas chromatographic analysis as consisting of ca. 95% of the required 2,3,5,6-tetrafluorotoluene and ca. 5% of 2,3,5,6-tetrafluoro-1,4-xylene. When the addition was kept at -45° C After a period of 30 minutes the mixture was allowed to warm to the ambient temperature poured into distilled water the mixture extracted with diethyl ether (2×50 ml) the extracts dried over anhydrous magnesium sulphate After filtering the solution was concentrated by evaporation of the solvents at atmospheric pressure The residual oil was distilled boiling in the range 115°-122° C. at atmospheric pressure (6.2 g) collected