4-Nitrochlorobenzene

4-Nitrochlorobenzene is prepared industrially by nitration of chlorobenzene:

ClC₆H₅ + HNO₃ → ClC₆H₄NO₂ + H₂O

This reaction affords both the 2- and the 4-nitro derivatives, in about a 1:2 ratio. These isomers are separated by a combination of crystallization and distillation.[2] 4-Nitrochlorobenzene was originally prepared by the nitration of 4-bromochlorobenzene by Holleman and coworkers.[3]

4-Nitrochlorobenzene is an intermediate in the preparation of a variety of derivatives. Nitration gives 2,4-dinitrochlorobenzene, and 3,4-dichloronitrobenzene. Reduction with iron metal gives 4-chloroaniline. The electron-withdrawing nature of the appended nitro-group makes the benzene ring especially susceptible to nucleophilic aromatic substitution, unlike related chlorobenzene. Thus, the strong nucleophiles hydroxide, methoxide, fluoride, and amide displace chloride to give respectively 4-nitrophenol, 4-nitroanisole, 4-fluoronitrobenzene, and 4-nitroaniline.[2][4]

Another use of 4-nitrochlorobenzene is its condensation with aniline to produce 4-nitrodiphenylamine. Reductive alkylation of the nitro group affords secondary aryl amines, which are useful antioxidants for rubber.

4-Nitrochlorobenzene is the precursor to the anti-leprosy drug Dapsone (4-[(4-aminobenzene)sulfonyl]aniline).[2]

The U.S. National Institute for Occupational Safety and Health considers 4-nitrochlorobenzene as a potential occupational carcinogen.[5] The Occupational Safety and Health Administration set a permissible exposure limit of 1 mg/m³ The American Conference of Governmental Industrial Hygienists recommends an airborne exposure limit of 0.64 mg/m³ over a time-weighted average of eight hours.[6][7]