Editing Nitration

{{short description|Chemical reaction which adds a nitro (–NO₂) group onto a molecule}}
{{Distinguish|Nitrification|Nitrosation|Nitriding}}

In [[organic chemistry]], '''nitration''' is a general class of [[chemical process]]es for the introduction of a [[nitro group]] ({{chem2|\sNO2}}) into an [[organic compound]]. The term also is applied incorrectly to the different process of forming [[nitrate ester]]s ({{chem2|\sONO2}}) between [[Alcohol (chemistry)|alcohol]]s and [[nitric acid]] (as occurs in the [[Organic synthesis|synthesis]] of [[nitroglycerin]]). The difference between the resulting [[molecular structure]]s of nitro compounds and [[nitrate]]s ({{chem2|NO3-}}) is that the [[nitrogen]] atom in nitro compounds is directly [[Chemical bond|bonded]] to a non-[[oxygen]] atom (typically [[carbon]] or another nitrogen atom), whereas in nitrate esters (also called organic nitrates), the nitrogen is bonded to an oxygen atom that in turn usually is bonded to a carbon atom (nitrito group). 

There are many major industrial applications of nitration in the strict sense; the most important by volume are for the production of nitroaromatic compounds such as [[nitrobenzene]]. The technology is long-standing and mature.<ref>*{{cite book|author=Schofield, K.|title=Nitration and Aromatic Reactivity|publisher=Cambridge University Press|location=Cambridge|year=1971}}</ref><ref name="Booth"/><ref>{{cite book|last1=Olahfirst1=G.A.|last2=Malhotra|first2=R.|last3=Narang|first3=S.C. |title=Nitration: Methods and Mechanisms|publisher=VCH|location=
NY|year=1989|isbn= 978-0-471-18695-3}}</ref>

:[[File:Nitration_reaction_equation_example.svg|frameless|303x303px]]

Nitration reactions are notably used for the production of explosives, for example the conversion of [[guanidine]] to [[nitroguanidine]] and the conversion of [[toluene]] to [[trinitrotoluene]] (TNT). Nitrations are, however, of wide importance as virtually all aromatic amines ([[aniline]]s) are produced from nitro precursors. Millions of tons of nitroaromatics are produced annually.<ref name="Booth">{{cite encyclopedia|author=Gerald Booth|title=Nitro Compounds, Aromatic|encyclopedia=Ullmann's Encyclopedia of Industrial Chemistry|year=2007|publisher=Wiley-VCH|location=Weinheim|doi=10.1002/14356007.a17_411|isbn=978-3527306732}}</ref>

==Aromatic nitration==
Typical nitrations of aromatic compounds rely on a reagent called "mixed acid", a mixture of concentrated [[nitric acid]] and [[sulfuric acid]]s.<ref>John McMurry Organic Chemistry 2nd Ed.</ref><ref name="Booth"/> This mixture produces the [[nitronium ion]] (NO<sub>2</sub><sup>+</sup>), which is the active species in '''aromatic nitration'''. This active ingredient, which can be isolated in the case of [[nitronium tetrafluoroborate]],<ref>{{OrgSynth | title = Benzonitrile, 2-methyl-3,5-dinitro- | author = [[George A. Olah]] and Stephen J. Kuhn | collvol = 5 | collvolpages = 480 | prep=cv5p0480}}</ref> also effects nitration without the need for the mixed acid. In mixed-acid syntheses sulfuric acid is not consumed and hence acts as a [[catalyst]] as well as an absorbent for water.  In the case of nitration of [[benzene]], the reaction is conducted at a warm temperature, not exceeding 50&nbsp;°C.<ref>{{Cite web|url=https://www.chemguide.co.uk/organicprops/arenes/nitration.html|title=Nitration of benzene and methylbenzene}}</ref> The process is one example of [[electrophilic aromatic substitution]], which involves the attack by the electron-rich [[benzene]] ring:

:[[Image:AromaticNitrationMechanism.svg|Aromatic nitration mechanism]]

Alternative mechanisms have also been proposed, including one involving [[single electron transfer]] (SET).<ref>{{cite journal | title = Unified Mechanism Concept of Electrophilic Aromatic Nitration Revisited: Convergence of Computational Results and Experimental Data |author1=Esteves, P. M. |author2=Carneiro, J. W. M. |author3=Cardoso, S. P. |author4=Barbosa, A. G. H. |author5=Laali, K. K. |author6=Rasul, G. |author7=Prakash, G. K. S. |author8=e Olah, G. A. | journal = [[J. Am. Chem. Soc.]] | year = 2003 | doi = 10.1021/ja021307w | volume = 125 | pages = 4836–49 | pmid = 12696903 | issue = 16}}</ref><ref>{{cite journal | title = Electrophilic Aromatic Nitration: Understanding Its Mechanism and Substituent Effects |author1=Queiroz, J. F. |author2=Carneiro, J. W. M. |author3=Sabino A. A. |author4=Sparapan, R. |author5=Eberlin, M. N. |author6=Esteves, P. M. | journal = [[J. Org. Chem.]] | doi = 10.1021/jo0609475 | year = 2006 | volume = 71 | pages = 6192–203 | pmid = 16872205 | issue = 16}}</ref>

==Scope==
Selectivity can be a challenge.  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 acid]]s in place of sulfuric acid.<ref name="Booth"/> 

[[Regioselectivity]] is strongly affected by substituents on aromatic rings (see [[electrophilic aromatic substitution]]). For example, nitration of nitrobenzene gives all three isomers of [[dinitrobenzene]]s in a ratio of 93:6:1 (respectively meta, ortho, para).<ref>{{March6th|page=665}} </ref> Electron-withdrawing groups such as other [[nitro compound|nitro]] are [[Deactivating group|deactivating]]. Nitration is accelerated by the presence of [[activating group]]s such as [[amino]], [[Hydroxyl|hydroxy]] and [[methyl]] groups also [[amide]]s and [[ether]]s resulting in para and ortho isomers.  In addition to regioselectivity, the degree of nitration is of interest.  [[Fluorenone]], for example, can be selectively trinitrated<ref>{{OrgSynth | title = 2,4,7-Trinitrofluorenone | author = E. O. Woolfolk and Milton Orchin | collvol = 3 | collvolpages = 837 | prep=cv3p0837}}</ref> or tetranitrated.<ref>{{OrgSynth | title = 2,4,5,7-Tetranitrofluorenone | author = Melvin S. Newman and H. Boden | collvol = 5 | collvolpages = 1029 | prep=cv5p1029}}</ref>

The direct nitration of [[aniline]] with [[nitric acid]] and [[sulfuric acid]], according to one source,<ref>Web resource: [http://www.warren-wilson.edu/~research/Undergrad_Res/nss97-98/abstrspr98.htm warren-wilson.edu] {{Webarchive|url=https://web.archive.org/web/20120320060521/http://www.warren-wilson.edu/~research/Undergrad_Res/nss97-98/abstrspr98.htm |date=2012-03-20 }}</ref> results in a 50/50 mixture of ''para''- and ''meta''-nitroaniline isomers. In this reaction the fast-reacting and activating aniline (ArNH<sub>2</sub>) exists in equilibrium with the more abundant but less reactive (deactivated) anilinium ion (ArNH<sub>3</sub><sup>+</sup>), which may explain this reaction product distribution. According to another source,<ref>''Mechanism and synthesis'' Peter Taylor, Royal Society of Chemistry (Great Britain), Open University</ref> a more controlled nitration of aniline starts with the formation of [[acetanilide]] by reaction with [[acetic anhydride]] followed by the actual nitration. Because the amide is a regular activating group the products formed are the para and ortho isomers. Heating the reaction mixture is sufficient to hydrolyze the amide back to the nitrated aniline.

===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.<ref>Louw, Robert "Acetyl nitrate" e-EROS Encyclopedia of Reagents for Organic Synthesis 2001, 1-2. {{doi| 10.1002/047084289X.ra032}}</ref><ref>{{cite journal |doi=10.1021/jo981557o |title=A Novel Method for the Nitration of Simple Aromatic Compounds |date=1998 |last1=Smith |first1=Keith |last2=Musson |first2=Adam |last3=Deboos |first3=Gareth A. |journal=The Journal of Organic Chemistry |volume=63 |issue=23 |pages=8448–8454 }}</ref>

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.<ref>{{Cite journal |last=Yang |first=Tao |last2=Li |first2=Xiaoqian |last3=Deng |first3=Shuang |last4=Qi |first4=Xiaotian |last5=Cong |first5=Hengjiang |last6=Cheng |first6=Hong-Gang |last7=Shi |first7=Liangwei |last8=Zhou |first8=Qianghui |last9=Zhuang |first9=Lin |date=2022-09-26 |title=From N–H Nitration to Controllable Aromatic Mononitration and Dinitration─The Discovery of a Versatile and Powerful N -Nitropyrazole Nitrating Reagent |url=https://pubs.acs.org/doi/10.1021/jacsau.2c00413 |journal=JACS Au |language=en |volume=2 |issue=9 |pages=2152–2161 |doi=10.1021/jacsau.2c00413 |issn=2691-3704 |pmc=9516713 |pmid=36186553}}</ref>

===Ipso nitration===
With aryl chlorides, [[triflate]]s and nonaflates, [[Arene substitution pattern#Ipso.2C meso.2C and peri substitution|ipso]] nitration may also take place.<ref>{{Cite journal| doi = 10.1002/anie.200906940| pmid = 20146295| year = 2010| last1 = Prakash | first1 = G.| last2 = Mathew | first2 = T.| title = Ipso-Nitration of Arenes| volume = 49| issue = 10| pages = 1726–1728| journal = Angewandte Chemie International Edition in English }}</ref> The phrase '''ipso nitration''' was first used by Perrin and Skinner in 1971, in an investigation into chloroanisole nitration.<ref>{{Cite journal| doi = 10.1021/ja00743a015| title = Directive effects in electrophilic aromatic substitution ("ipso factors"). Nitration of haloanisoles| year = 1971| last1 = Perrin | first1 = C. L.| last2 = Skinner | first2 = G. A.| journal = Journal of the American Chemical Society| volume = 93| issue = 14| pages = 3389 }}</ref> In one protocol, 4-chloro-''n''-butylbenzene is reacted with [[sodium nitrite]] in [[tert-butanol|''t''-butanol]] in the presence of  0.5&nbsp;mol% [[Tris(dibenzylideneacetone)dipalladium(0)|Pd<sub>2</sub>(dba)<sub>3</sub>]], a biarylphosphine ligand and a [[phase-transfer catalyst]] to provide 4-nitro-''n''-butylbenzene.<ref>{{Cite journal| doi = 10.1021/ja905768k| pmid = 19737014| year = 2009| last1 = Fors | first1 = B.| last2 = Buchwald | first2 = S.| title = Pd-Catalyzed Conversion of Aryl Chlorides, Triflates, and Nonaflates to Nitroaromatics| journal = Journal of the American Chemical Society| volume = 131| issue = 36| pages = 12898–12899| pmc = 2773681}}</ref>

== See also ==
* [[Menke nitration]]
* [[Zincke nitration]]
* [[Reactive nitrogen species]]

== References ==
{{reflist}}
{{Organic reactions}}
[[Category:Nitration reactions]]
[[Category:Substitution reactions]]