4-Nitrochlorobenzene

4-Nitrochlorobenzene is prepared industrially by nitration of chlorobenzene:[2]

${\displaystyle \mathrm {ClC_{6}H_{5}+HNO_{3}\rightarrow ClC_{6}H_{4}NO_{2}+H_{2}O} }$

This reaction affords both the 2- and the 4-nitro derivatives, in about a 1:2 ratio. These isomers are separated by distillation. 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, and amide displace chloride to give respectively 4-nitrophenol, 4-nitroanisole, 4-nitroaniline.[2]

Another major 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 National Institute for Occupational Safety and Health considers 4-nitrochlorobenzene as a potential occupational carcinogen that may be absorbed through the skin.[4] The Occupational Safety and Health Administration set a permissible exposure limit of 1 mg/m³, while 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.[5][6]