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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: |
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: |
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<div>{{pad|1em}}[[File:Benzol.svg|x60px|Benzene]] |
<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> |
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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).<ref>{{Ullmann|last=Gerald|first=Booth|title=Nitro Compounds, Aromatic|doi=10.1002/14356007.a17_411}}</ref> |
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).<ref>{{Ullmann|last=Gerald|first=Booth|title=Nitro Compounds, Aromatic|doi=10.1002/14356007.a17_411}}</ref> |
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[[Chloramphenicol]] is a rare example of a [[natural product|naturally occurring]] nitro compound. At least some naturally occurring nitro groups arose by the oxidation of amino groups.<ref>{{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}}</ref> [[2-Nitrophenol]] is an aggregation [[pheromone]] of [[tick]]s. |
[[Chloramphenicol]] is a rare example of a [[natural product|naturally occurring]] nitro compound. At least some naturally occurring nitro groups arose by the oxidation of amino groups.<ref>{{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}}</ref> [[2-Nitrophenol]] is an aggregation [[pheromone]] of [[tick]]s. |
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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. 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> |
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> |
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=== In pharmaceuticals === |
=== In pharmaceuticals === |
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== Reactions== |
== Reactions== |
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Nitro compounds participate in several [[organic reaction]]s, the most important being |
Nitro compounds participate in several [[organic reaction]]s, the most important being [[reduction of nitro compounds]] to the corresponding amines: |
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:RNO<sub>2</sub> + 3 H<sub>2</sub> → RNH<sub>2</sub> + 2 H<sub>2</sub>O |
:RNO<sub>2</sub> + 3 H<sub>2</sub> → RNH<sub>2</sub> + 2 H<sub>2</sub>O |
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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> |
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> |
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The [[locant|α-carbon]] of nitroalkanes is somewhat acidic. The p''K''<sub>a</sub> values of [[nitromethane]] and [[2-nitropropane]] are respectively 17.2 and 16.9 in [[dimethyl sulfoxide]] (DMSO) solution, suggesting an aqueous p''K''<sub>a</sub> 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> |
The [[locant|α-carbon]] of nitroalkanes is somewhat acidic. The p''K''<sub>a</sub> values of [[nitromethane]] and [[2-nitropropane]] are respectively 17.2 and 16.9 in [[dimethyl sulfoxide]] (DMSO) solution, suggesting an aqueous p''K''<sub>a</sub> 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> |
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Nitronates are also key intermediates in the [[Nef reaction]]: when exposed to |
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. 16-3.</ref> |
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[[Grignard reagent]]s combine with nitro compounds to give a [[nitrone]]; but a Grignard reagent with an |
[[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> |
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===Dye syntheses=== |
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⚫ | 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]]. |
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===Biochemical reactions=== |
===Biochemical reactions=== |
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Many [[Flavin group|flavin]]-dependent [[enzyme]]s 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.<ref>{{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}}</ref> |
Many [[Flavin group|flavin]]-dependent [[enzyme]]s 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.<ref>{{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}}</ref> |
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===Ring-closures=== |
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⚫ | 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]]. |
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===Explosions=== |
===Explosions=== |
Inorganic chemistry, nitro compounds are organic compounds that contain one or more nitro functional groups (−NO2). The nitro group is one of the most common explosophores (functional group that makes a compound explosive) used globally. The nitro group is also strongly electron-withdrawing. Because of this property, C−H 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.[1]
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 (NO+2), 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).[3] 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:
Innucleophilic aliphatic substitution, sodium nitrite (NaNO2) replaces an alkyl halide. In the so-called Ter Meer reaction (1876) named after Edmund ter Meer,[14] the reactant is a 1,1-halonitroalkane:
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.[15] When the same reactant is reacted with potassium hydroxide the reaction product is the 1,2-dinitro dimer.[16]
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.[17] 2-Nitrophenol is an aggregation pheromoneofticks.
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.[18] Nitrophenylethane is also found in members of the Annonaceae, Lauraceae and Papaveraceae.[19]
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.[20]
Nitro compounds participate in several organic reactions, the most important being reduction of nitro compounds to the corresponding amines:
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:[21]
The α-carbon of nitroalkanes is somewhat acidic. The pKa values of nitromethane and 2-nitropropane are respectively 17.2 and 16.9 in dimethyl sulfoxide (DMSO) solution, suggesting an aqueous pKa of around 11.[22] 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 directlytoaldehydes, and, with enones, can serve as a Michael donor. Conversely, a nitroalkene reacts with enols as a Michael acceptor.[23][24]
Nitronates are also key intermediates in the Nef reaction: when exposed to acids or oxidants, a nitronate hydrolyzes to a carbonyl and azanone.[25]
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.[26]
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.[27]
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.
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Hydrocarbons (only C and H) |
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Only carbon, hydrogen, and oxygen (only C, H and O) |
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Only one element, not being carbon, hydrogen, or oxygen (one element, not C, H or O) |
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Nitrogen species
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Hydrides |
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Organic |
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Oxides |
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Halides |
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Oxidation states |