4-Nitrochlorobenzene

4-Nitrochlorobenzene is the organic compound with the formula ClC₆H₄NO₂. It is a pale yellow solid. 4-Nitrochlorobenzene is a common intermediate in the production of a number of industrially useful compounds, including antioxidants commonly found in rubber. Other isomers with the formula ClC₆H₄NO₂ include 2-nitrochlorobenzene and 3-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]

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.^[4] In another example, 4-nitrochlorobenzene is a favored substrate for cross-coupling reactions.^[5]

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][6]

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.

El Instituto Nacional de Seguridad y Salud Ocupacional de EE. UU. considera el 4-nitroclorobenceno como un posible carcinógeno ocupacional. ^{[ 7 ]} La Administración de Seguridad y Salud Ocupacional estableció un límite de exposición permisible de 1 mg/m³ ^. La Conferencia Estadounidense de Higienistas Industriales Gubernamentales recomienda un límite de exposición en el aire de 0,64 mg/m³ ^durante un promedio ponderado en el tiempo de ocho horas. ^{[ 8 ] [ 9 ]}