1-(chloromethyl)-4-fluoro-2-methylbenzene

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

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

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: 1-(Chloromethyl)-4-fluoro-2-methylbenzene (12.8 g, 81 mmol) was dissolved in CH2Cl2 (50 mL) and to the resultant solution was added a mixture of tetrabutylammonium hydrogensulphate (1.4 g, 4.0 mmol), NaOH (0.32 g, 8.1 mmol) and water (50 mL) followed by an aqueous solution of potassium cyanide (5.0 g, 77 mmol). The mixture was stirred for 5 minutes and then the pH of the aqueous layer was monitored and adjusted to the alkaline side by the dropwise addition of aqueous sodium hydroxide (5M). The mixture was refluxed for one hour, stirred at room temperature overnight and then diluted with CH2Cl2 (50 mL). The organic layer was washed thrice with water and then dried over Na2SO4. The solvent was removed by evaporation and the product was purified by chromatography on silica gel using CH2Cl2. There was obtained 11.1 g (92%) of (4-fluoro-2-methylphenyl)acetonitrile as an oil. 1H NMR (300 MHz, CDCl3): 2.3 (s, 3H), 3.6 (s, 2H), 6.8-7.0 (m, 2H), 7.3 (m, 1H). was added The mixture was refluxed for one hour stirred at room temperature overnight The organic layer was washed thrice with water dried over Na2SO4 The solvent was removed by evaporation the product was purified by chromatography on silica gel

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

Procedure: 1-(Chloromethyl)-4-fluoro-2-methylbenzene (12.8 g, 81 mmol) was dissolved in CH2Cl2 (50 mL) and to the resultant solution was added a mixture of tetrabutylammonium hydrogensulphate (1.4 g, 4.0 mmol), NaOH (0.32 g, 8.1 mmol) and water (50 mL) followed by an aqueous solution of potassium cyanide (5.0 g, 77 mmol). The mixture was stirred for 5 minutes and then the pH of the aqueous layer was monitored and adjusted to the alkaline side by the dropwise addition of aqueous sodium hydroxide (5M). The mixture was refluxed for one hour, stirred at room temperature overnight and then diluted with CH2Cl2 (50 mL). The organic layer was washed thrice with water and then dried over Na2SO4. The solvent was removed by evaporation and the product was purified by chromatography on silica gel using CH2Cl2. There was obtained 11.1 g (92%) of (4-fluoro-2-methylphenyl)acetonitrile as an oil. 1H NMR (300 MHz, CDCl3): 2.3 (s, 3H), 3.6 (s, 2H), 6.8-7.0 (m, 2H), 7.3 (m, 1H). was added The mixture was refluxed for one hour stirred at room temperature overnight The organic layer was washed thrice with water dried over Na2SO4 The solvent was removed by evaporation the product was purified by chromatography on silica gel

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

Procedure: (4-Fluoro-2-methylphenyl)methanol (11.5 g, 82 mmol) was dissolved in CH2Cl2 (100 mL). The mixture was cooled to 0° C. before adding SOCl2 (10.7 g, 90 mmol), then stirred for 30 min at 0° C. and then at room temperature for 1.5 h. The solvent and excess of SOCl2 were removed by evaporation followed by the addition of CH2Cl2. The solvent and remaining traces of SOCl2 were evaporated once more. There was obtained 13.0 g (100%) of 1-(chloromethyl)-4-fluoro-2-methylbenzene as an oil. 1H NMR (300 MHz, CDCl3): 2.4 (s, 3H), 4.6 (s, 2H), 6.8-7.0 (m, 2H), 7.3 (m, 1H). at room temperature for 1.5 h The solvent and excess of SOCl2 were removed by evaporation followed by the addition of CH2Cl2 were evaporated once more

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

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: A mixture of 16 parts of 1-(chloromethyl)-4-fluoro-2-methylbenzene, 7.8 parts of a solution of potassium cyanide in a small amount of water, 0.1 parts of potassium iodide and 240 parts of 2-propanone is stirred and refluxed for 22 hours. The reaction mixture is cooled and filtered. The filtrate is evaported. The residue is taken up in water and the product is extracted with methylbenzene. The extract is dried, filtered and evaporated, yielding 13 parts (87.2%) of 4-fluoro-2-methylbenzeneacetonitrile as a residue. refluxed for 22 hours The reaction mixture is cooled filtered the product is extracted with methylbenzene The extract is dried filtered evaporated

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

Procedure: To 14.3 parts of thionyl chloride is added dropwise a solution of 14 parts of 4-fluoro-2-methylbenzenemethanol and 0.9 parts of N,N-dimethylformamide in 45 parts of methylbenzene while cooling in ice-water. Then there are added 135 parts of methylbenzene and stirring is continued for 1 hour at room temperature. The reaction mixture is evaporated, yielding 17 parts (100%) of 1-(chloromethyl)-4-fluoro-2-methylbenzene as a residue. The reaction mixture is evaporated