4-Nitrochlorobenzene

4-Nitrochlorobenzene is prepared industrially by nitration of chlorobenzene: : 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. The chloride substituent in 4-nitrochlorobenzene is more labile than in chlorobenzene. For example, it is readily displaced by sulfide nucleophiles, leading the way to 4-nitrothiophenol. In another example, 4-nitrochlorobenzene is a favored substrate for cross-coupling reactions. ==Applications==

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. 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. drug Dapsone (4-[(4-aminobenzene)sulfonyl]aniline). ==Safety==

The U.S. National Institute for Occupational Safety and Health considers 4-nitrochlorobenzene as a potential occupational carcinogen. 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. ==References==