Nitro compound#Reduction

File:PhNO2&metric.png, distances in picometers.{{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}}]]

Aromatic nitro compounds are typically synthesized by nitration. Nitration is achieved using a mixture of nitric acid and sulfuric acid, which produce the nitronium ion ({{chem2|NO2+}}), which is the electrophile:

The nitration product produced on the largest scale, by far, is nitrobenzene. Many explosives are produced by nitration including trinitrophenol (picric acid), trinitrotoluene (TNT), and trinitroresorcinol (styphnic acid).{{Ullmann|last=Gerald|first=Booth|title=Nitro Compounds, Aromatic|doi=10.1002/14356007.a17_411}}

Another but more specialized method for making aryl–NO₂ group starts from halogenated phenols, is the Zinke nitration.

Aliphatic nitro compounds can be synthesized by various methods; notable examples include:

• Free radical nitration of alkanes.{{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}} The reaction produces fragments from the parent alkane, creating a diverse mixture of products; for instance, nitromethane, nitroethane, 1-nitropropane, and 2-nitropropane are produced by treating propane with nitric acid in the gas phase (e.g. 350–450 °C and 8–12 atm).
• Nucleophilic substitution reactions between halocarbons{{cite journal|last1=Kornblum|first1=N.|last2=Ungnade|first2=H. E.|title=1-Nitroöctane|journal=Organic Syntheses|date=1963|volume=4|page=724|doi=10.15227/orgsyn.038.0075}} or organosulfates{{cite journal|last1=Walden|first1=P.|title=Zur Darstellung aliphatischer Sulfocyanide, Cyanide und Nitrokörper|journal=Berichte der Deutschen Chemischen Gesellschaft|date=1907|volume=40|issue=3|pages=3214–3217|doi=10.1002/cber.19070400383|url=https://zenodo.org/record/1426247}} with silver or alkali nitrite salts.
• Nitromethane can be produced in the laboratory by treating sodium chloroacetate with sodium nitrite.{{cite journal|last1=Whitmore|first1=F. C.|last2=Whitmore|first2=Marion G.|title=Nitromethane|journal=Organic Syntheses|date=1923|volume=1|page=401|doi=10.15227/orgsyn.003.0083}}
• Oxidation of oximes{{cite journal|last1=Olah|first1=George A.|last2=Ramaiah|first2=Pichika|last3=Chang-Soo|first3=Lee|last4=Prakash|first4=Surya|title=Convenient Oxidation of Oximes to Nitro Compounds with Sodium Perborate in Glacial Acetic Acid|journal=Synlett|date=1992|volume=1992|issue=4|pages=337–339|doi=10.1055/s-1992-22006}} or primary amines.{{cite journal|last1=Ehud|first1=Keinan|last2=Yehuda|first2=Mazur|title=Dry ozonation of amines. Conversion of primary amines to nitro compounds|journal=The Journal of Organic Chemistry|date=1977|volume=42|issue=5|pages=844–847|doi=10.1021/jo00425a017}}
• Reduction of β-nitro alcohols{{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 }} or nitroalkenes.{{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 }}
• By decarboxylation of α-nitro carboxylic acids formed from nitriles and ethyl nitrate.{{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}}{{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}}

In nucleophilic aliphatic substitution, sodium nitrite (NaNO₂) replaces an alkyl halide. In the so-called Ter Meer reaction (1876) named after Edmund ter Meer,{{cite journal

| author = Edmund ter Meer

| title = Ueber Dinitroverbindungen der Fettreihe

| journal = Justus Liebigs Annalen der Chemie

| volume = 181

| issue = 1

| pages = 1–22

| year = 1876

| doi = 10.1002/jlac.18761810102| url = https://zenodo.org/record/1427353

| author-link = Edmund ter Meer

}} the reactant is a 1,1-halonitroalkane:

:File:Ter Meer Reaction.svg

The reaction mechanism is proposed in which in the first slow step a 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.{{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}} When the same reactant is reacted with potassium hydroxide the reaction product is the 1,2-dinitro dimer.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])

Chloramphenicol is a rare example of a naturally occurring nitro compound. At least some naturally occurring nitro groups arose by the oxidation of amino groups.{{cite journal |doi=10.1016/j.jmb.2007.06.014 |pmid=17765264 |title=Structure and Action of the N-oxygenase AurF from Streptomyces thioluteus |journal=Journal of Molecular Biology |volume=373 |issue=1 |pages=65–74 |year=2007 |last1=Zocher |first1=Georg |last2=Winkler |first2=Robert |last3=Hertweck |first3=Christian |last4=Schulz |first4=Georg E}} 2-Nitrophenol is an aggregation pheromone of ticks.

Examples of nitro compounds are rare in nature. 3-Nitropropionic acid found in fungi and plants (Indigofera). Nitropentadecene is a defense compound found in termites. Aristolochic acids are found in the flowering plant family Aristolochiaceae. Nitrophenylethane is found in Aniba canelilla.{{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 }} Nitrophenylethane is also found in members of the Annonaceae, Lauraceae and Papaveraceae.{{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}}

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.{{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 }}

Nitro compounds participate in several organic reactions, the most important being reduction of nitro compounds to the corresponding amines:

:RNO₂ + 3 H₂ → RNH₂ + 2 H₂O

Virtually all 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:{{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}}

File:Nitrohydrogenation.svg

The α-carbon of nitroalkanes is somewhat acidic. The pK_a values of nitromethane and 2-nitropropane are respectively 17.2 and 16.9 in dimethyl sulfoxide (DMSO) solution, suggesting an aqueous pK_a of around 11.{{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}} In other words, these carbon acids can be deprotonated in aqueous solution. The conjugate base is called a nitronate, and behaves similar to an enolate. In the nitroaldol reaction, it adds directly to aldehydes, and, with enones, can serve as a Michael donor. Conversely, a nitroalkene reacts with enols as a Michael acceptor.{{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}}{{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}} Nitrosating a nitronate gives a nitrolic acid.{{cite book|title=Nitrosation|first=D. L. H.|last=Williams|publisher=Cambridge University|location=Cambridge, UK|year=1988|isbn=0-521-26796-X|url=https://archive.org/details/nitrosation0000will|url-access=registration|page=44}}

Nitronates are also key intermediates in the Nef reaction: when exposed to acids or oxidants, a nitronate hydrolyzes to a carbonyl and azanone.Smith (2020)), March's Organic Chemistry, rxn. 16-3.

Grignard reagents 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.{{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}}

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

Many flavin-dependent enzymes are capable of oxidizing aliphatic nitro compounds to less-toxic aldehydes and ketones. Nitroalkane oxidase and 3-nitropropionate oxidase oxidize aliphatic nitro compounds exclusively, whereas other enzymes such as glucose oxidase have other physiological substrates.{{cite journal|last1=Nagpal|first1=Akanksha|first2=Michael P. |last2=Valley |first3=Paul F. |last3=Fitzpatrick |first4=Allen M. |last4=Orville |date=2006|title=Crystal Structures of Nitroalkane Oxidase: Insights into the Reaction Mechanism from a Covalent Complex of the Flavoenzyme Trapped during Turnover|journal=Biochemistry|pmid=16430210|doi=10.1021/bi051966w|volume=45|issue=4|pmc=1855086|pages=1138–50}}

Explosive decomposition of organo nitro compounds are redox reactions, wherein both the oxidant (nitro group) and the fuel (hydrocarbon substituent) are bound within the same molecule. The explosion process generates heat by forming highly stable products including molecular nitrogen (N₂), carbon dioxide, and water. The explosive power of this redox reaction is enhanced because these stable products are gases at mild temperatures. Many contact explosives contain the nitro group.

• Functional group
• Reduction of nitro compounds
• Nitration
• Nitrite (also an NO₂ group, but bonds differently)
• Nitroalkene
• Nitroglycerin

{{Reflist}}

{{Commons category|Nitro compounds}}

{{Functional groups}}

{{Nitrogen compounds}}

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Category:Functional groups