Nitro compound: Difference between revisions

{{Short description|Organic compound containing an −NO₂ group}}

{{see also|Transition metal nitrite complex}}

{{Use dmy dates|date=December 2022}}

[[File:Nitro-group.svg|thumb|right|150px|The structure of an organic nitro compound]]

In [[organic chemistry]], '''nitro compounds''' are [[organic compound]]s that contain one or more '''nitro''' [[functional group]]s ({{chem2|\sNO2}}). The nitro group is one of the most common [[explosophore]]s (functional group that makes a compound explosive) used globally. The nitro group is also strongly [[electron-withdrawing group|electron-withdrawing]]. Because of this property, {{chem2|[[Carbon–hydrogen bond|C\sH]]}} bonds alpha (adjacent) to the nitro group can be acidic. For similar reasons, the presence of nitro groups in aromatic compounds retards [[electrophilic aromatic substitution]] but facilitates [[nucleophilic aromatic substitution]]. Nitro groups are rarely found in nature. They are almost invariably produced by nitration reactions starting with [[nitric acid]].<ref>{{cite book |title=Nitro and Nitroso Groups: Part 2, Volume 2 |year=1970 |editor=Henry Feuer |isbn=978-0-470-77117-4 |doi=10.1002/9780470771174 |publisher=John Wiley & Sons Ltd. |series=PATAI'S Chemistry of Functional Groups|volume=2 }}{{cite book |title=Nitro and Nitroso Groups: Supplement F: Part 2, Volume 2 |year=1982 |editor=Saul Patai |isbn=978-0-470-77167-9 |doi=10.1002/9780470771679 |publisher=John Wiley & Sons Ltd. |series=PATAI'S Chemistry of Functional Groups}}{{cite book |title=Amino, Nitroso and Nitro Compounds and Their Derivatives: Supplement F: Part 1, Volume 1 |year=1982 |editor=Saul Patai |isbn=978-0-470-77166-2 |doi=10.1002/9780470771662 |publisher=John Wiley & Sons Ltd. |series=PATAI'S Chemistry of Functional Groups}}</ref>

[[File:PhNO2&metric.png|thumb|144px|Structural details of [[nitrobenzene]], distances in picometers.<ref>{{cite journal |journal=Structural Chemistry |year=2007 |volume=18 |issue=6 |pages=739–753 |title=Molecular Structure and Conformation of Nitrobenzene Reinvestigated by Combined Analysis of Gas-Phase Electron Diffraction, Rotational Constants, and Theoretical Calculations |author=Olga V. Dorofeeva |author2=Yuriy V. Vishnevskiy |author3=Natalja Vogt |author4=Jürgen Vogt |author5=Lyudmila V. Khristenko |author6=Sergey V. Krasnoshchekov |author7=Igor F. Shishkov |author8=István Hargittai |author9=Lev V. Vilkov |doi=10.1007/s11224-007-9186-6 |s2cid=98746905}}</ref>]]

<div>{{pad|1em}}[[File:Benzol.svg|x60px|Benzene]] + [[File:Nitronium ion vert.svg|x60px|Nitronium ion]] {{Biochem reaction subunit|direction=forward|for_prod={{H+|nolink=y}}|imagesize=60px|container_style=vertical-align:middle}} [[File:Nitrobenzol.svg|x100px|Nitrobenzene]]</div>

*[[Free radical]] [[nitration]] of [[alkane]]s.<ref>{{cite journal|last1=Markofsky|first1=Sheldon|last2=Grace|first2=W.G.|title=Nitro Compounds, Aliphatic|journal=Ullmann's Encyclopedia of Industrial Chemistry|date=2000|doi=10.1002/14356007.a17_401|isbn=978-3-527-30673-2}}</ref> The reaction produces fragments from the parent alkane, creating a diverse mixture of products; for instance, [[nitromethane]], [[nitroethane]], [[1-Nitropropane|1-nitropropane]], and [[2-Nitropropane|2-nitropropane]] are produced by treating [[propane]] with [[nitric acid]] in the gas phase (e.g. 350–450&nbsp;°C and 8–12 [[Atmosphere (unit)|atm]]).

*Reduction of [[Henry reaction|β-nitro alcohols]]<ref>{{cite journal |last1=Chandrasekhar |first1=S. |last2=Shrinidhi |first2=A. |title=Useful Extensions of the Henry Reaction: Expeditious Routes to Nitroalkanes and Nitroalkenes in Aqueous Media |journal=Synthetic Communications |date=2014 |volume=44 |issue=20 |pages=3008–3018 |doi=10.1080/00397911.2014.926373|s2cid=98439096 |url=https://figshare.com/articles/journal_contribution/1053153 }}</ref> or [[nitroalkene]]s.<ref>{{cite journal |last1=Shrinidhi |first1=A. |title=Microwave-assisted chemoselective reduction of conjugated nitroalkenes to nitroalkanes with aqueous tri-n-butyltin hydride |journal=Cogent Chemistry |date=2015 |volume=1 |issue=1 |page=1061412 |doi=10.1080/23312009.2015.1061412|doi-access=free }}</ref>

*By [[decarboxylation]] of [[alpha and beta carbon|α]]-nitro [[carboxylic acid]]s formed from [[nitriles]] and [[ethyl nitrate]].<ref>{{cite journal|last1=Wislicenus|first1=Wilhelm|last2=Endres|first2=Anton|title=Ueber Nitrirung mittels Aethylnitrat [Nitrification by means of ethyl nitrate]|journal=Berichte der Deutschen Chemischen Gesellschaft|date=1902|volume=35|issue=2|pages=1755–1762|doi=10.1002/cber.190203502106|url=https://zenodo.org/record/1426046}}</ref><ref>{{cite book|last1=Weygand|first1=Conrad|editor1-last=Hilgetag|editor1-first=G.|editor2-last=Martini|editor2-first=A.|title=Weygand/Hilgetag Preparative Organic Chemistry|date=1972|publisher=John Wiley & Sons, Inc.|location=New York|isbn=978-0-471-93749-4|page=1007|edition=4th}}</ref>

The [[reaction mechanism]] is proposed in which in the first slow step a [[Hydron (chemistry)|proton]] is abstracted from nitroalkane '''1''' to a [[carbanion]] '''2''' followed by [[protonation]] to an aci-nitro '''3''' and finally [[nucleophilic displacement]] of chlorine based on an experimentally observed hydrogen [[kinetic isotope effect]] of 3.3.<ref>{{cite journal |doi=10.1021/ja01600a048 |title=Aci-Nitroalkanes. I. The Mechanism of the ter Meer Reaction1 |journal=Journal of the American Chemical Society |volume=78 |issue=19 |pages=4980–4984 |year=1956 |last1=Hawthorne |first1=M. Frederick}}</ref> When the same reactant is reacted with [[potassium hydroxide]] the reaction product is the 1,2-dinitro dimer.<ref>''3-Hexene, 3,4-dinitro-'' D. E. Bisgrove, J. F. Brown, Jr., and L. B. Clapp. ''[[Organic Syntheses]]'', Coll. Vol. 4, p. 372 (1963); Vol. 37, p. 23 (1957). ([http://www.orgsynth.org/orgsyn/pdfs/CV4P0372.pdf Article])</ref>

Examples of nitro compounds are rare in nature. [[3-Nitropropionic acid]] found in [[fungus|fungi]] and plants (''[[Indigofera]]''). [[Nitropentadecene]] is a defense compound found in [[termite]]s. [[Aristolochic acid|Aristolochic acids]] are found in the flowering plant family [[Aristolochiaceae]]. Nitrophenylethane is found in ''Aniba canelilla''.<ref>{{cite journal | last1=Maia | first1=José Guilherme S. | last2=Andrade | first2=Eloísa Helena A. | title=Database of the Amazon aromatic plants and their essential oils | journal=Química Nova | publisher=FapUNIFESP (SciELO) | volume=32 | issue=3 | year=2009 | issn=0100-4042 | doi=10.1590/s0100-40422009000300006 | pages=595–622 |url=http://www.scielo.br/pdf/qn/v32n3/a06v32n3.pdf| doi-access=free }}</ref> Nitrophenylethane is also found in members of the [[Annonaceae]], [[Lauraceae]] and [[Papaveraceae]].<ref>{{cite book | last1=Kramer | first1=K.U. | last2=Kubitzki | first2=K. | last3=Rohwer | first3=J.G. | last4=Bittrich | first4=V. | title=Flowering Plants, Dicotyledons: Magnoliid, Hamamelid, and Caryophyllid Families | publisher=Springer-Verlag, Berlin | series=Families and genera of vascular plants | year=1993 | isbn=978-3-540-55509-4 | url=https://books.google.com/books?id=K_pGAAAAYAAJ}}</ref>

Despite the occasional use in pharmaceuticals, the nitro group is associated with [[mutagenicity]] and [[genotoxicity]] and therefore is often regarded as a liability in the [[drug discovery]] process.<ref name="pmid30295477">{{cite journal |vauthors=Nepali K, Lee HY, Liou JP |title=Nitro-Group-Containing Drugs |journal=J. Med. Chem. |volume=62 |issue=6 |pages=2851–2893 |date=March 2019 |pmid=30295477 |doi=10.1021/acs.jmedchem.8b00147 |s2cid=52931949 }}</ref>

== Reactions==

Nitro compounds participate in several [[organic reaction]]s, the most important being [[reduction of nitro compounds]] to the corresponding amines:

Virtually all [[arylamine|aromatic amines]] (e.g. [[aniline]]) are derived from nitroaromatics through such [[catalytic hydrogenation]]. A variation is formation of a dimethylaminoarene with [[palladium on carbon]] and [[formaldehyde]]:<ref>{{cite journal |title=ETHYL p-DIMETHYLAMINOPHENYLACETATE |journal= Organic Syntheses|year= 1967|volume=47|page= 69|url=http://orgsyn.org/Content/pdfs/procedures/cv5p0552.pdf |doi=10.15227/orgsyn.047.0069}}</ref>

[[File:Nitrohydrogenation.svg|500px|center|Nitro compound hydrogenation]]

The [[locant|α-carbon]] of nitroalkanes is somewhat acidic. The p''K''_a values of [[nitromethane]] and [[2-nitropropane]] are respectively 17.2 and 16.9 in [[dimethyl sulfoxide]] (DMSO) solution, suggesting an aqueous p''K''_a of around 11.<ref>{{cite journal | doi = 10.1021/ja00099a004| title = Is Resonance Important in Determining the Acidities of Weak Acids or the Homolytic Bond Dissociation Enthalpies (BDEs) of Their Acidic H-A Bonds?| journal = Journal of the American Chemical Society| volume = 116| issue = 20| page = 8885| year = 1994| last1 = Bordwell| first1 = Frederick G| last2 = Satish| first2 = A. V}}</ref> In other words, these [[carbon acid]]s can be deprotonated in aqueous solution. The conjugate base is called a [[nitronate]], and behaves similar to an [[enolate]]. In the [[nitroaldol reaction]], it [[direct addition|adds directly]] to [[aldehyde]]s, and, with [[enone]]s, can serve as a [[Michael reaction|Michael donor]]. Conversely, a [[nitroalkene]] reacts with enols as a Michael acceptor.<ref>{{cite journal|author1=Ranganathan, Darshan |author2=Rao, Bhushan |author3=Ranganathan, Subramania |author4=Mehrotra, Ashok |author5=Iyengar, Radha |name-list-style=amp |title=Nitroethylene: a stable, clean, and reactive agent for organic synthesis|journal=The Journal of Organic Chemistry|year=1980|volume=45|issue=7|pages=1185–1189|doi=10.1021/jo01295a003}}</ref><ref>{{cite journal|author1=Jubert, Carole |author2=Knochel, Paul |name-list-style=amp |title=Preparation of polyfunctional nitro olefins and nitroalkanes using the copper-zinc reagents RCu(CN)ZnI|journal=The Journal of Organic Chemistry|year=1992|volume=57|issue=20|pages=5431–5438|doi=10.1021/jo00046a027}}</ref>

Nitronates are also key intermediates in the [[Nef reaction]]: when exposed to acids or oxidants, a nitronate hydrolyzes to a [[carbonyl group|carbonyl]] and [[azanone]].<ref>Smith (2020)), ''March's Organic Chemistry'', rxn.&nbsp;16-3.</ref>

[[Grignard reagent]]s combine with nitro compounds to give a [[nitrone]]; but a Grignard reagent with an α hydrogen will then add again to the nitrone to give a [[hydroxylamine]] salt.<ref>{{cite journal|doi=10.1021/jo00048a012|title=Nitrones from addition of benzyl and allyl Grignard reagents to alkyl nitro compounds: chemo-, regio-, and stereoselectivity of the reaction|first1=Giuseppe|last1=Bartoli|first2=Enrico|last2=Marcantoni|first3=Marino|last3=Petrini|orig-date=14 Apr 1992|publisher=American Chemical Society|journal=Journal of Organic Chemistry|volume=57|number=22|year=1992|pages=5834–5840}}</ref>

===Dye syntheses===

The [[Leimgruber-Batcho indole synthesis|Leimgruber–Batcho]], [[Bartoli indole synthesis|Bartoli]] and [[Baeyer-Emmerling indole synthesis|Baeyer–Emmerling]] indole syntheses begin with aromatic nitro compounds. [[Indigo dye|Indigo]] can be synthesized in a condensation reaction from [[nitrobenzaldehyde|''ortho''-nitrobenzaldehyde]] and [[acetone]] in strongly basic conditions in a reaction known as the [[Baeyer–Drewson indigo synthesis]].

{{Reflist}}

{{Nitrogen compounds}}