1-(bromomethyl)-2,3,4,5,6-pentafluorobenzene

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

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The toluene solution from Stage 1 was mixed with triphenyl phosphine (1 g) and heated at 130° C. for 3 hours. After cooling, the solution was diluted with diethyl ether (5 cm3) and the title compound filtered off, washed with hexane (4×5 cm3) and dried by suction. After cooling the title compound filtered off washed with hexane (4×5 cm3) dried by suction

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of phosphorus tribromide (2.1 g) and toluene (1 cm3) was added dropwise to a solution of 2,3,4,5,6-pentafluorobenzylalcohol (3.4 g) and pyridine (0.21 g) in toluene (10 cm3) at 0° C. The reaction mixture was stirred at 0° C. for 45 minutes, then at the ambient temperature (ca. 20° C.) for 75 minutes, and was then added to an excess of saturated sodium bicarbonate solution. The products were extracted into diethyl ether, and the combined ether layers dried and concentrated by evaporation under reduced pressure. The residual solution (still containing toluene) was passed through a plug of silica gel. at the ambient temperature (ca. 20° C.) for 75 minutes The products were extracted into diethyl ether the combined ether layers dried concentrated by evaporation under reduced pressure

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

Procedure: By following the similar procedure in Synthesis Example 1 by using 5-aminosalicylic acid (500 mg, 3.26 mmole) and pentafluorobenzyl bromide (1.02 g, 3.92 mmole), 650 mg (60% yield) of 5-(pentafluorobenzyl)aminosalicylic acid was obtained as a white solid.: mp>190° C. (decompose). in Synthesis Example 1

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

Procedure: Synthesized by 1:2 ratio of 3',5'-dihydroxyacetophenone to pentafluorobenzyl bromide. Yield: 98%. m.p. 102°-103° C. 1H NMR, δ: 2.60 (s, 3H, CH3CO), 5.22 (s, 4H, CH2O), 6.83 (bs, 1H, H--C4'), 7.24 (d, 2H, J=1.8 Hz, H--C2' & H--C6') ppm; 13C NMR, δ: 26.0 (CH3CO), 57.4 (CH2O), 106.4 (C4'), 107.4 (C2' & C6'), 109.7 (C1", 2JC-F =17 Hz), 137.4 (C2" & C6", JC-F =249 Hz), 139.2 (C1'), 141.7 (C4", JC-F =256 Hz), 145.7 (C3" & C5", JC-F =251 Hz), 159.2 (C3' & C5'), 196.7 (C=O) ppm. MS(EI): 331 ([M-PFBz]+); MS(ECNI): 331 ([M-PFBz]-, 100%).

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

Procedure: A mixture of 2,6-dimethylphenol (5 mmol), pentafluorobenzyl bromide (1.3 g, 5 mmol), potassium carbonate (5 g), acetone (30 ml), and 18-crown-6 ether (0.1 g) were stirred under reflux for 5 hours. Work-up procedure was the same as above. Yield: 96%; m.p.: 81°-82° C.; 1H NMR, δ: 2.37 (s, 6H, CH3), 4.91 (s, 2H, CH2O), 6.96-7.16 (m, 3H, H--Ar) ppm; 13C NMR, δ: 15.7 (CH3), 59.9 (CH2O), 110.7 (C2', 2JC-F =18 Hz), 124.6 (C4), 129.0 (C3 & C5), 131.1 (C2 & C6), 137.6 (C2' & C6', JC-F =253 Hz), 141.7 (C4', JC-F =255 Hz), 145.9 (C3' & C5', JC-F =250 Hz), 154.6 (C1) ppm. under reflux for 5 hours

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

Procedure: 10.7 g (0.033 mol) of the potassium salt of 2,2-dimethyl-3-(2-chloro-2-p-chlorophenyl-vinyl)-cyclopropanecarboxylic acid were dissolved in 100 ml of dimethylformamide and the solution was heated to 120° C., together with 6.8 g (0.026 mol) of pentafluorobenzyl bromide, for 3 hours. After the reaction had ended, the dimethylformamide was distilled off in vacuo and the residue which remained was taken up in 200 ml of methylene chloride. The methylene chloride solution was then extracted by shaking twice with 100 ml of water each time, the organic phase was dried over sodium sulphate and the solvent was stripped off in vacuo. Last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg. 9.0 g (74.4% of theory) of pentafluoro-benzyl 2,2-dimethyl-3-(2-chloro-2-p-chloro-phenyl-vinyl)-cyclopropanecarboxylate were obtained as a yellow oil with the refractive index nD25 :1.5382. the dimethylformamide was distilled off in vacuo The methylene chloride solution was then extracted the organic phase was dried over sodium sulphate Last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg

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

Procedure: 10.7 g (0.033 mol) of the potassium salt of 2,2-dimethyl-3-(2-chloro-2-p-chlorophenyl-vinyl)-cyclopropanecarboxylic acid were dissolved in 100 ml of dimethylformamide and the solution was heated to 120° C., together with 6.8 g (0.026 mol) of pentafluorobenzyl bromide, for 3 hours. After the reaction had ended, the dimethylformamide was distilled off in vacuo and the residue which remained was taken up in 200 ml of methylene chloride. The methylene chloride solution was then extracted by shaking twice with 100 ml of water each time, the organic phase was dried over sodium sulphate and the solvent was stripped off in vacuo. Last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg. 9.0 g (74.4% of theory) of pentafluoro-benzyl 2,2-dimethyl-3-(2-chloro-2-p-chloro-phenyl-vinyl)-cyclopropanecarboxylate were obtained as a yellow oil with the refractive index nD25 :1.5382. the dimethylformamide was distilled off in vacuo The methylene chloride solution was then extracted the organic phase was dried over sodium sulphate Last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg

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

Procedure: 3.6 g (0.0165 mol) of the potassium salt of 2,2-dimethyl-3-cyclobutylidenemethylcyclopropanecarboxylic acid were dissolved in 50 ml of dimethylformamide and the solution was heated to 110° C., together with 4.3 g (0.0165 mol) of pentafluorobenzyl bromide, for 3 hours. After the reaction had ended, the reaction mixture was poured into 150 ml of water and extracted twice with 100 ml of methylene chloride each time. The organic phase was then extracted by shaking twice with 100 ml of water each time and then dried over sodium sulphate. The solvent was stripped off in vacuo and last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg. 4.0 g (67.1% of theory) of pentafluorobenzyl 2,2-dimethyl-3-cyclobutylidenemethylcyclopropanecaboxylate were obtained as a brown oil with the refractive index nD30 :1.4850. extracted twice with 100 ml of methylene chloride each time The organic phase was then extracted dried over sodium sulphate were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg

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

Procedure: 3.6 g (0.0165 mol) of the potassium salt of 2,2-dimethyl-3-cyclobutylidenemethylcyclopropanecarboxylic acid were dissolved in 50 ml of dimethylformamide and the solution was heated to 110° C., together with 4.3 g (0.0165 mol) of pentafluorobenzyl bromide, for 3 hours. After the reaction had ended, the reaction mixture was poured into 150 ml of water and extracted twice with 100 ml of methylene chloride each time. The organic phase was then extracted by shaking twice with 100 ml of water each time and then dried over sodium sulphate. The solvent was stripped off in vacuo and last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg. 4.0 g (67.1% of theory) of pentafluorobenzyl 2,2-dimethyl-3-cyclobutylidenemethylcyclopropanecaboxylate were obtained as a brown oil with the refractive index nD30 :1.4850. extracted twice with 100 ml of methylene chloride each time The organic phase was then extracted dried over sodium sulphate were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg

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

Procedure: A five-liter, three-necked flask equipped with a mechanical stirrer, reflux condenser, and thermometer was charged with toluene (3.3 liters), triphenylphosphine (686 g, 2.62 mole), and pentafluorobenzyl bromide (343 g, 1.31 mole). The contents were stirred and heated slowly to reflux. A white precipitate formed as the reaction progressed. At the completion of the reaction the flask was cooled to ambient temperature and the solid product was filtered and washed with hot toluene (2.6 liters). These solids were dried in a vacuum desiccator to give a 90% yield of pentafluorobenzyltriphenylphosphonium bromide. A five-liter, three-necked flask equipped with a mechanical stirrer reflux condenser heated slowly to reflux A white precipitate formed as the reaction At the completion of the reaction the flask the solid product was filtered washed with hot toluene (2.6 liters) These solids were dried in a vacuum desiccator

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

Procedure: A five-liter, three-necked flask equipped with a mechanical stirrer, reflux condenser, and thermometer was charged with toluene (3.3 liters), triphenylphosphine (686 g, 2.62 mole), and pentafluorobenzyl bromide (343 g, 1.31 mole). The contents were stirred and heated slowly to reflux. A white precipitate formed as the reaction progressed. At the completion of the reaction the flask was cooled to ambient temperature and the solid product was filtered and washed with hot toluene (2.6 liters). These solids were dried in a vacuum desiccator to give a 90% yield of pentafluorobenzyltriphenylphosphonium bromide. A five-liter, three-necked flask equipped with a mechanical stirrer reflux condenser heated slowly to reflux A white precipitate formed as the reaction At the completion of the reaction the flask the solid product was filtered washed with hot toluene (2.6 liters) These solids were dried in a vacuum desiccator