Sodium Cyanide → 4-Bromo-2,6-dimethylbenzonitrile

Temperature

0 °C

4-Bromo-2,6-dimethylphenylamine (10 g, 500 mmol) was suspended in concentrated HCl (10 mL) and crushed ice (41 g) and cooled to 0° C. NaNO2 (3.52 g, 51 mmol) in water (10 mL) was added, maintaining a temperature of 0° C. and the reaction was stirred for 30 minutes. A solution of copper cyanide (5.60 g, 62.5 mmol) in water (25 mL) and sodium cyanide (7.79 g, 159 mmol) in water (12 mL) were cooled to 0° C. in a separate flask. The concentrated HCl mixture was neutralized with sodium carbonate and the resulting diazonium salt mixture was added to the copper cyanide and sodium cyanide solution along with toluene (100 mL) under vigorous stirring, maintaining a temperature of 0° C. for 1 hour, followed by stirring at room temperature for 4 hours. The reaction mixture was heated to 50° C. and then cooled to room temperature. The reaction was partitioned between water and toluene and the organic layers were combined and washed with water and dried over anhydrous Na2SO4. The product was purified by column chromatography on silica (20% EtOAc/Hexanes) to afford a brown solid (8.10 g). 1H NMR (300 MHz, CDCl3): δ 7.33 (s, 2H), 2.53 (s, 6H).

1. temperaturemaintaining a temperature of 0° C.
2. temperaturemaintaining a temperature of 0° C. for 1 hour
3. stirringby stirring at room temperature for 4 hours
4. temperatureThe reaction mixture was heated to 50° C.
5. temperaturecooled to room temperature
6. customThe reaction was partitioned between water and toluene
7. washwashed with water
8. dry with materialdried over anhydrous Na2SO4
9. customThe product was purified by column chromatography on silica (20% EtOAc/Hexanes)

ORD record

ord-bce9b9b1e65f42b29ed4c8253f1479b8

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968570B2