Nitration

In organic chemistry, nitration refers to a chemical processes which introduce the −NO2 moiety to an organic compound. Depending on substrate, the product is either a nitro group, nitramide, or nitrate ester.

The technology is long-standing and mature, and has many major industrial applications. The volumetrically most important is aromatic nitration, in which a nitronium ion equivalent attacks an aromatic ring. Nitroaromats are produced annually on the megaton scale, the feedstocks for virtually all aromatic amine (aniline) production.

Nitration reactions are also central to explosives manufacture, because the −NO2 moiety is an explosophore. Examples include the conversion of guanidine to nitroguanidine and toluene to trinitrotoluene (TNT).

Aromatic nitration

Typical aromatic nitrations rely on a reagent called "mixed acid", a mixture of concentrated nitric acid and sulfuric acids. The reaction has been called "probably the most potentially hazardous industrially operated unit process" because thermal runaway is difficult to avoid. For benzene nitration, the reaction temperature is controlled to not exceed 50 °C.

The active ingredient in mixed acid is the nitronium ion (NO2+), also isolable as the nitrating agent nitronium tetrafluoroborate. Sulfuric acid is not consumed, acting as a desiccating catalyst.

Aromatic nitration is generally accepted to occur through electrophilic aromatic substitution on the electron-rich benzene ring:

Aromatic nitration mechanism

This has been difficult to rationalize with certain competition experiments: whichever NO±,0
2 intermediate is involved cannot distinguish between electron-poor and electron-rich rings. Alternative mechanisms, including single electron transfer (SET) have been proposed.

On the other hand, any proposed reactive intermediate must have a very strong preference for electrophilically activated sites on the ring. For example, nitration of nitrobenzene gives all three isomers of dinitrobenzenes in a ratio of 93% meta, 6% ortho, and 1% para.

The current understanding of the reaction is that the nitronium ion and arene initially associate in a (half-sandwich) π complex. This barrier-free diffusion-controlled association is rapid and unselective. Reorganization to form the Wheland intermediate then requires solvent relaxation, which is slow enough to produce the observed site selectivity.

Scope

In addition to regioselectivity, the degree of nitration is of interest. Fluorenone, for example, can be selectively trinitrated or tetranitrated.

Often alternative products act as contaminants or are simply wasted. Considerable attention thus is paid to optimization of the reaction conditions. For example, the mixed acid can be derived from phosphoric or perchloric acids in place of sulfuric acid.

Alternatives to nitric acid

Mixture of nitric and acetic acids or nitric acid and acetic anhydride is commercially important in the production of RDX, as amines are destructed by sulfuric acid. Acetyl nitrate had also been used as a nitration agent.

In the Wolffenstein–Böters reaction, benzene reacts with nitric acid and mercury(II) nitrate to give picric acid.

In the second half of the 20th century, new reagents were developed for laboratory usage, mainly N-nitro heterocyclic compounds.

Ipso nitration

With aryl chlorides, triflates and nonaflates, ipso nitration may also take place. The phrase ipso nitration was first used by Perrin and Skinner in 1971, in an investigation into chloroanisole nitration. In one protocol, 4-chloro-n-butylbenzene is reacted with sodium nitrite in t-butanol in the presence of 0.5 mol% Pd2(dba)3, a biarylphosphine ligand and a phase-transfer catalyst to provide 4-nitro-n-butylbenzene.

See also

References

  1. ↑ Schofield, K. (1971). Nitration and Aromatic Reactivity. Cambridge: Cambridge University Press.
  2. ↑ Olah, G.A.; Malhotra, R.; Narang, S.C. (1989). Nitration: Methods and Mechanisms. NY: VCH. ISBN 978-0-471-18695-3.
  3. 1 2 3 4 Gerald Booth (2007). "Nitro Compounds, Aromatic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a17_411. ISBN 978-3527306732.
  4. ↑ John McMurry Organic Chemistry 2nd Ed.
  5. ↑ "Nitration of benzene and methylbenzene".
  6. ↑ George A. Olah and Stephen J. Kuhn. "Benzonitrile, 2-methyl-3,5-dinitro-". Organic Syntheses; Collected Volumes, vol. 5, p. 480.
  7. ↑ Esteves, P. M.; Carneiro, J. W. M.; Cardoso, S. P.; Barbosa, A. G. H.; Laali, K. K.; Rasul, G.; Prakash, G. K. S.; e Olah, G. A. (2003). "Unified Mechanism Concept of Electrophilic Aromatic Nitration Revisited: Convergence of Computational Results and Experimental Data". J. Am. Chem. Soc. 125 (16): 4836–49. doi:10.1021/ja021307w. PMID 12696903.
  8. ↑ Queiroz, J. F.; Carneiro, J. W. M.; Sabino A. A.; Sparapan, R.; Eberlin, M. N.; Esteves, P. M. (2006). "Electrophilic Aromatic Nitration: Understanding Its Mechanism and Substituent Effects". J. Org. Chem. 71 (16): 6192–203. doi:10.1021/jo0609475. PMID 16872205.
  9. 1 2 Wagen, Corin (10 Sep 2022). "Singleton Saturday: Nitration of toluene". Corin Wagen's blog. Retrieved 2026-11-11.
  10. ↑ Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, p. 665, ISBN 978-0-471-72091-1
  11. ↑ E. O. Woolfolk and Milton Orchin. "2,4,7-Trinitrofluorenone". Organic Syntheses; Collected Volumes, vol. 3, p. 837.
  12. ↑ Melvin S. Newman and H. Boden. "2,4,5,7-Tetranitrofluorenone". Organic Syntheses; Collected Volumes, vol. 5, p. 1029.
  13. ↑ Louw, Robert "Acetyl nitrate" e-EROS Encyclopedia of Reagents for Organic Synthesis 2001, 1-2. doi:10.1002/047084289X.ra032
  14. ↑ Smith, Keith; Musson, Adam; Deboos, Gareth A. (1998). "A Novel Method for the Nitration of Simple Aromatic Compounds". The Journal of Organic Chemistry. 63 (23): 8448–8454. doi:10.1021/jo981557o.
  15. ↑ Yang, Tao; Li, Xiaoqian; Deng, Shuang; Qi, Xiaotian; Cong, Hengjiang; Cheng, Hong-Gang; Shi, Liangwei; Zhou, Qianghui; Zhuang, Lin (2022-09-26). "From N–H Nitration to Controllable Aromatic Mononitration and Dinitration─The Discovery of a Versatile and Powerful N -Nitropyrazole Nitrating Reagent". JACS Au. 2 (9): 2152–2161. doi:10.1021/jacsau.2c00413. ISSN 2691-3704. PMC 9516713. PMID 36186553.
  16. ↑ Prakash, G.; Mathew, T. (2010). "Ipso-Nitration of Arenes". Angewandte Chemie International Edition in English. 49 (10): 1726–1728. doi:10.1002/anie.200906940. PMID 20146295.
  17. ↑ Perrin, C. L.; Skinner, G. A. (1971). "Directive effects in electrophilic aromatic substitution ("ipso factors"). Nitration of haloanisoles". Journal of the American Chemical Society. 93 (14): 3389. Bibcode:1971JAChS..93.3389P. doi:10.1021/ja00743a015.
  18. ↑ Fors, B.; Buchwald, S. (2009). "Pd-Catalyzed Conversion of Aryl Chlorides, Triflates, and Nonaflates to Nitroaromatics". Journal of the American Chemical Society. 131 (36): 12898–12899. Bibcode:2009JAChS.13112898F. doi:10.1021/ja905768k. PMC 2773681. PMID 19737014.