2-hydroxy-3-methylbenzonitrile

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

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

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a heated (45° C.), stirred solution of 2-cyano-6-methylphenol (5 g) in glacial acetic acid (32 mL) was added a solution of fuming nitric acid (3.2 mL) in acetic acid (12 mL). After 1 h at elevated temperature (45° C.), the reaction mixture was cooled (to 0° C.), water added and partitioned between DEE/water. The organic phase was washed with water, brine, dried over sodium sulfate and concentrated in vacuo to afford a solid. Recrystallization from DEE afforded the title compound as yellow crystals (3.6 g). added partitioned between DEE/water The organic phase was washed with water, brine dried over sodium sulfate concentrated in vacuo to afford a solid Recrystallization from DEE

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

Procedure: A solution of 2-hydroxy-3-methylbenzaldehyde (18.6 g), hydroxylamine hydrochloride (14.2 g) and sodium formate (19.2 g) in formic acid (200 mL) was heated at reflux for 18 h, then cooled and partitioned between DEE/water. The organic layer was washed with water, saturated aqueous sodium bicarbonate and brine, then dried over sodium sulfate and concentrated in vacuo to afford a solid. Recrystallization from diethyl ether/petroleum ether afforded the title compound as colorless crystals (15.0 g). at reflux for 18 h cooled partitioned between DEE/water The organic layer was washed with water, saturated aqueous sodium bicarbonate and brine dried over sodium sulfate concentrated in vacuo to afford a solid Recrystallization from diethyl ether/petroleum ether

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

Procedure: A solution of 2-hydroxy-3-methylbenzaldehyde (18.6 g), hydroxylamine hydrochloride (14.2 g) and sodium formate (19.2 g) in formic acid (200 mL) was heated at reflux for 18 h, then cooled and partitioned between DEE/water. The organic layer was washed with water, saturated aqueous sodium bicarbonate and brine, then dried over sodium sulfate and concentrated in vacuo to afford a solid. Recrystallization from diethyl ether/petroleum ether afforded the title compound as colorless crystals (15.0 g). at reflux for 18 h cooled partitioned between DEE/water The organic layer was washed with water, saturated aqueous sodium bicarbonate and brine dried over sodium sulfate concentrated in vacuo to afford a solid Recrystallization from diethyl ether/petroleum ether

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

Procedure: A solution of 2-hydroxy-3-methyl-benzaldehyde (1.13 g, 8.29 mmol), hydroxylamine hydrochloride (0.69 g, 9.9 mmol) and sodium acetate (0.8 g, 9.9 mmol) in formic acid (20 ml) is heated at reflux over night. The solvent is evaporated under reduced pressure and the residue is partitioned between water and ethyl acetate. The organic phase is dried and evaporated to dryness. Chromatography yields the title compound. (CDCl3, 400 MHz): 7.32 (m, 2H); 6.89 (t, 1H); 5.65 (s, 1H); 2.23 (s, 3H). at reflux over night The solvent is evaporated under reduced pressure the residue is partitioned between water and ethyl acetate The organic phase is dried evaporated to dryness

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

Procedure: A solution of 2-hydroxy-3-methyl-benzaldehyde (1.13 g, 8.29 mmol), hydroxylamine hydrochloride (0.69 g, 9.9 mmol) and sodium acetate (0.8 g, 9.9 mmol) in formic acid (20 ml) is heated at reflux over night. The solvent is evaporated under reduced pressure and the residue is partitioned between water and ethyl acetate. The organic phase is dried and evaporated to dryness. Chromatography yields the title compound. (CDCl3, 400 MHz): 7.32 (m, 2H); 6.89 (t, 1H); 5.65 (s, 1H); 2.23 (s, 3H). at reflux over night The solvent is evaporated under reduced pressure the residue is partitioned between water and ethyl acetate The organic phase is dried evaporated to dryness

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of potassium carbonate (1.24 g, 8.9 mmol), 2-hydroxy-3-methylbenzonitrile (0.3 g, 2.25 mmol) and ω-bromo-2-ethoxyacetophenone (0.55 g, 2.25 mmol) in dry DMF (10 ml) is stirred at 60° C. for 20 h. The reaction mixture is diluted with ethyl acetate and the resulting solution is washed repeatedly with brine. Drying of the solution over sodium sulfate, filtering and evaporation of the solvent leaves the crude product. Purification on silicagel yields the title compound in pure form. (CDCl3, 400 MHz): 7.53 (d, 2H); 7.41 (m, 2H); 7.14-6.99 (m, 3H); 5.79 (bs, 2H); 4.09 (q, 2H); 2.36 (s, 3H); 1.17 (t, 3H). the resulting solution is washed repeatedly with brine Drying of the solution over sodium sulfate filtering evaporation of the solvent leaves the crude product Purification on silicagel

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

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

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a heated (45° C.), stirred solution of 2-cyano-6-methylphenol (5 g) in glacial acetic acid (32 mL) was added a solution of fuming nitric acid (3.2 mL) in acetic acid (12 mL). After 1 h at elevated temperature (45° C.), the reaction mixture was cooled (to 0° C.), water added and partitioned between DEE/water. The organic phase was washed with water, brine, dried over sodium sulfate and concentrated in vacuo to afford a solid. Recrystallization from DEE afforded the title compound as yellow crystals (3.6 g). added partitioned between DEE/water The organic phase was washed with water, brine dried over sodium sulfate concentrated in vacuo to afford a solid Recrystallization from DEE

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

Procedure: A solution of 2-hydroxy-3-methylbenzaldehyde (18.6 g), hydroxylamine hydrochloride (14.2 g) and sodium formate (19.2 g) in formic acid (200 mL) was heated at reflux for 18 h, then cooled and partitioned between DEE/water. The organic layer was washed with water, saturated aqueous sodium bicarbonate and brine, then dried over sodium sulfate and concentrated in vacuo to afford a solid. Recrystallization from diethyl ether/petroleum ether afforded the title compound as colorless crystals (15.0 g). at reflux for 18 h cooled partitioned between DEE/water The organic layer was washed with water, saturated aqueous sodium bicarbonate and brine dried over sodium sulfate concentrated in vacuo to afford a solid Recrystallization from diethyl ether/petroleum ether