4-Amino-3-chlorobenzonitrile → 3-Chloro-4-nitrobenzonitrile

Temperature

0 °C

To an ice cold solution of 4-amino-3-chlorobenzonitrile (1 g, 6.6 mmol) in concentrated HCl (2.5 mL) plus water (2.5 mL) a chilled solution of sodium nitrite (0.74 g, 1.62 eq) in water (3.6 mL) is added dropwise to maintain the reaction temperature <0° C. After stirring at 0° C. for 10 min, the mixture is added portion-wise to an ice cold solution of sodium nitrite (3.29 g, 7.22 eq) and copper(I) oxide (349 mg, 0.37 eq) in water 14.5 mL). Stirring is continued at 0° C. for 40 min, and then at room temperature for 0.5 h. The reaction mixture is extracted with dichloromethane (2×), the combined organic layers washed with saturated aqueous sodium chloride, dried (MgSO4), concentrated, and purified by silica gel chromatography to give 4-nitro-3-chlorobenzonitrile. 1H NMR (CDCl3): δ 7.96 (d, J=8.24 Hz, 1h), 7.88 (d, J=1.65 Hz, 1H), 7.63 (dd, J=1.65, 8.24 Hz, 1H.

1. temperatureto maintain the reaction temperature <0° C
2. stirringStirring
3. waitis continued at 0° C. for 40 min
4. waitat room temperature for 0.5 h
5. extractionThe reaction mixture is extracted with dichloromethane (2×)
6. washthe combined organic layers washed with saturated aqueous sodium chloride
7. dry with materialdried (MgSO4)
8. concentrationconcentrated
9. custompurified by silica gel chromatography

ORD record

ord-0afc771df3f348d49f7f5d87e26015b0

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06916819B2