3,5-dihydroxybenzonitrile

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: To a mixture of 3,5-dihydroxybenzonitrile (1.08 g, 8 mmol) and K2CO3 (1.104 g, 8 mmol) in CH3CN (50 mL), benzyl bromide (1.438 g, 8 mmol) was added. The mixture was heated to reflux for 2 hours. Solvent was evaporated under vacuum. The residue was treated with EtOAc (200 mL) and 1M HCl (200 mL). The organic layer was washed, dried, and evaporated in vacuo. The residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH) to give 3-benzyloxy-5-hydroxybenzonitrile (529 mg, 29%), 3,5-dibenzyloxybenzonitryl (784 mg, 31%) and 256 mg (23.7 mg, 24%) of the starting material. The product 3-benzyloxy-5-hydroxybenzonitrile had: MP 144-145° C.; 1H NMR δ 9.15 (s, 1H, OH), 7.47 (d, 2H, J=7.0 Hz, 2′ and 6′), 7.40 (ddd, 2H, J=7.0, 7.0, 2.0 Hz, 3′ and 5′), 7.34 (dd, 1H, J=7.7 and 2.1 Hz, 4′), 6.89 (dd, 1H, J=1.5 Hz, 4), 6.78 (d, 2H, J=1.8 Hz), 5.16 (s, 2H). was added The mixture was heated to reflux for 2 hours Solvent was evaporated under vacuum The residue was treated with EtOAc (200 mL) and 1M HCl (200 mL) The organic layer was washed dried evaporated in vacuo The residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH)

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

Procedure: To a mixture of 3,5-dihydroxybenzonitrile (1.08 g, 8 mmol) and K2CO3 (1.104 g, 8 mmol) in CH3CN (50 mL), benzyl bromide (1.438 g, 8 mmol) was added. The mixture was heated to reflux for 2 hours. Solvent was evaporated under vacuum. The residue was treated with EtOAc (200 mL) and 1M HCl (200 mL). The organic layer was washed, dried, and evaporated in vacuo. The residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH) to give 3-benzyloxy-5-hydroxybenzonitrile (529 mg, 29%), 3,5-dibenzyloxybenzonitryl (784 mg, 31%) and 256 mg (23.7 mg, 24%) of the starting material. The product 3-benzyloxy-5-hydroxybenzonitrile had: MP 144-145° C.; 1H NMR δ 9.15 (s, 1H, OH), 7.47 (d, 2H, J=7.0 Hz, 2′ and 6′), 7.40 (ddd, 2H, J=7.0, 7.0, 2.0 Hz, 3′ and 5′), 7.34 (dd, 1H, J=7.7 and 2.1 Hz, 4′), 6.89 (dd, 1H, J=1.5 Hz, 4), 6.78 (d, 2H, J=1.8 Hz), 5.16 (s, 2H). 3,5-dibenzyloxybenzonitryl was added The mixture was heated to reflux for 2 hours Solvent was evaporated under vacuum The residue was treated with EtOAc (200 mL) and 1M HCl (200 mL) The organic layer was washed dried evaporated in vacuo The residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Caesium carbonate (2.41 g, 7.4 mmol) was added to a solution of 3,5-dihydroxy benzonitrile (1.0 g, 7.4 mmol) in dimethylformamide (5 ml) at room temperature and the mixture stirred for 10 minutes. Benzyl bromide (0.880 ml, 7.4 mmol) was added dropwise and the mixture heated at 80° C. for 30 minutes. The solvent was removed in vacuo, the residue treated with water (10 ml), acidified with aqueous hydrochloric acid (2M) and extracted with ethyl acetate (3×25 ml). The combined organic layers were washed with water (2×10 ml), brine (10 ml), dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography, eluting with ethyl acetate/pentane (20:80 to 50:50) to afford the title compound as a white solid in 26% yield, 445 mg. The solvent was removed in vacuo the residue treated with water (10 ml) extracted with ethyl acetate (3×25 ml) The combined organic layers were washed with water (2×10 ml), brine (10 ml) dried over sodium sulphate concentrated in vacuo The residue was purified by column chromatography eluting with ethyl acetate/pentane (20:80 to 50:50)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Caesium carbonate (2.41 g, 7.4 mmol) was added to a solution of 3,5-dihydroxy benzonitrile (1.0 g, 7.4 mmol) in dimethylformamide (5 ml) at room temperature and the mixture stirred for 10 minutes. Benzyl bromide (0.880 ml, 7.4 mmol) was added dropwise and the mixture heated at 80° C. for 30 minutes. The solvent was removed in vacuo, the residue treated with water (10 ml), acidified with aqueous hydrochloric acid (2M) and extracted with ethyl acetate (3×25 ml). The combined organic layers were washed with water (2×10 ml), brine (10 ml), dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography, eluting with ethyl acetate/pentane (20:80 to 50:50) to afford the title compound as a white solid in 26% yield, 445 mg. The solvent was removed in vacuo the residue treated with water (10 ml) extracted with ethyl acetate (3×25 ml) The combined organic layers were washed with water (2×10 ml), brine (10 ml) dried over sodium sulphate concentrated in vacuo The residue was purified by column chromatography eluting with ethyl acetate/pentane (20:80 to 50:50)

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

Procedure: To a mixture of 3,5-dihydroxybenzonitrile (1.08 g, 8 mmol) and K2CO3 (1.104 g, 8 mmol) in CH3CN (50 mL), benzyl bromide (1.438 g, 8 mmol) was added. The mixture was heated to reflux for 2 hours. Solvent was evaporated under vacuum. The residue was treated with EtOAc (200 mL) and 1M HCl (200 mL). The organic layer was washed, dried, and evaporated in vacuo. The residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH) to give 3-benzyloxy-5-hydroxybenzonitrile (529 mg, 29%), 3,5-dibenzyloxybenzonitryl (784 mg, 31%) and 256 mg (23.7 mg, 24%) of the starting material. The product 3-benzyloxy-5-hydroxybenzonitrile had: MP 144-145° C.; 1H NMR δ 9.15 (s, 1H, OH), 7.47 (d, 2H, J=7.0 Hz, 2′ and 6′), 7.40 (ddd, 2H, J=7.0, 7.0, 2.0 Hz, 3′ and 5′), 7.34 (dd, 1H, J=7.7 and 2.1 Hz, 4′), 6.89 (dd, 1H, J=1.5 Hz, 4), 6.78 (d, 2H, J=1.8 Hz), 5.16 (s, 2H). was added The mixture was heated to reflux for 2 hours Solvent was evaporated under vacuum The residue was treated with EtOAc (200 mL) and 1M HCl (200 mL) The organic layer was washed dried evaporated in vacuo The residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Caesium carbonate (2.41 g, 7.4 mmol) was added to a solution of 3,5-dihydroxy benzonitrile (1.0 g, 7.4 mmol) in dimethylformamide (5 ml) at room temperature and the mixture stirred for 10 minutes. Benzyl bromide (0.880 ml, 7.4 mmol) was added dropwise and the mixture heated at 80° C. for 30 minutes. The solvent was removed in vacuo, the residue treated with water (10 ml), acidified with aqueous hydrochloric acid (2M) and extracted with ethyl acetate (3×25 ml). The combined organic layers were washed with water (2×10 ml), brine (10 ml), dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography, eluting with ethyl acetate/pentane (20:80 to 50:50) to afford the title compound as a white solid in 26% yield, 445 mg. The solvent was removed in vacuo the residue treated with water (10 ml) extracted with ethyl acetate (3×25 ml) The combined organic layers were washed with water (2×10 ml), brine (10 ml) dried over sodium sulphate concentrated in vacuo The residue was purified by column chromatography eluting with ethyl acetate/pentane (20:80 to 50:50)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Caesium carbonate (2.41 g, 7.4 mmol) was added to a solution of 3,5-dihydroxy benzonitrile (1.0 g, 7.4 mmol) in dimethylformamide (5 ml) at room temperature and the mixture stirred for 10 minutes. Benzyl bromide (0.880 ml, 7.4 mmol) was added dropwise and the mixture heated at 80° C. for 30 minutes. The solvent was removed in vacuo, the residue treated with water (10 ml), acidified with aqueous hydrochloric acid (2M) and extracted with ethyl acetate (3×25 ml). The combined organic layers were washed with water (2×10 ml), brine (10 ml), dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography, eluting with ethyl acetate/pentane (20:80 to 50:50) to afford the title compound as a white solid in 26% yield, 445 mg. The solvent was removed in vacuo the residue treated with water (10 ml) extracted with ethyl acetate (3×25 ml) The combined organic layers were washed with water (2×10 ml), brine (10 ml) dried over sodium sulphate concentrated in vacuo The residue was purified by column chromatography eluting with ethyl acetate/pentane (20:80 to 50:50)

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

Procedure: To a mixture of 3,5-dihydroxybenzonitrile (1.08 g, 8 mmol) and K2CO3 (1.104 g, 8 mmol) in CH3CN (50 mL), benzyl bromide (1.438 g, 8 mmol) was added. The mixture was heated to reflux for 2 hours. Solvent was evaporated under vacuum. The residue was treated with EtOAc (200 mL) and 1M HCl (200 mL). The organic layer was washed, dried, and evaporated in vacuo. The residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH) to give 3-benzyloxy-5-hydroxybenzonitrile (529 mg, 29%), 3,5-dibenzyloxybenzonitryl (784 mg, 31%) and 256 mg (23.7 mg, 24%) of the starting material. The product 3-benzyloxy-5-hydroxybenzonitrile had: MP 144-145° C.; 1H NMR δ 9.15 (s, 1H, OH), 7.47 (d, 2H, J=7.0 Hz, 2′ and 6′), 7.40 (ddd, 2H, J=7.0, 7.0, 2.0 Hz, 3′ and 5′), 7.34 (dd, 1H, J=7.7 and 2.1 Hz, 4′), 6.89 (dd, 1H, J=1.5 Hz, 4), 6.78 (d, 2H, J=1.8 Hz), 5.16 (s, 2H). was added The mixture was heated to reflux for 2 hours Solvent was evaporated under vacuum The residue was treated with EtOAc (200 mL) and 1M HCl (200 mL) The organic layer was washed dried evaporated in vacuo The residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH)

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

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