4-Nitrochlorobenzene

Preparation and reactions

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.

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

References

1. {{PGCH. 0452
2. 4-Nitrochlorobenzene was originally prepared by the [[nitration]] of 4-bromochlorobenzene by Holleman and coworkers."The nitration of mixed dihalogen benzenes" Recueil des Travaux Chimiques des Pays-Bas et de la Belgique. Amsterdam, 1915; pp. 204-235.
3. (1946). "P-Nitrophenyl Disulfide, p-Nitrophenyl Sulfide and ''p''-Nitrothiophenol¹". Journal of the American Chemical Society.
4. (1999). "Highly Active Palladium Catalysts for Suzuki Coupling Reactions". Journal of the American Chemical Society.
5. Gerald Booth. (2007). "Nitro Compounds, Aromatic". Wiley-VCH.
6. (1934). "p-Nitrodiphenyl Ether". Organic Syntheses.
7. [https://www.cdc.gov/niosh/idlh/100005.html CDC - Immediately Dangerous to Life or Health Concentrations (IDLH): p-nitrochlorobenzene]
8. [https://www.cdc.gov/niosh/npg/npgd0452.html CDC - NIOSH Pocket Guide to Chemical Hazards]
9. [http://nj.gov/health/eoh/rtkweb/documents/fs/1549.pdf New Jersey Department of Health and Senior Services - Hazardous Substance Fact Sheet]