Inorganic chemistry,nitro compoundsareorganic compoundsthat contain one or morenitrofunctional groups(−NO2). The nitro group is one of the most commonexplosophores(functional group that makes a compound explosive) used globally. The nitro group is also stronglyelectron-withdrawing.Because of this property,C−Hbonds alpha (adjacent) to the nitro group can be acidic. For similar reasons, the presence of nitro groups in aromatic compounds retardselectrophilic aromatic substitutionbut facilitatesnucleophilic aromatic substitution.Nitro groups are rarely found in nature. They are almost invariably produced by nitration reactions starting withnitric acid.[1]
Synthesis
editPreparation of aromatic nitro compounds
edit
Aromatic nitro compounds are typically synthesized by nitration. Nitration is achieved using a mixture ofnitric acidandsulfuric acid,which produce thenitroniumion (NO+2), which is the electrophile:
+
The nitration product produced on the largest scale, by far, isnitrobenzene.Many explosives are produced by nitration includingtrinitrophenol(picric acid),trinitrotoluene(TNT), andtrinitroresorcinol(styphnic acid).[3] Another but more specialized method for making aryl–NO2group starts from halogenated phenols, is theZinke nitration.
Preparation of aliphatic nitro compounds
editAliphatic nitro compounds can be synthesized by various methods; notable examples include:
- Free radicalnitrationofalkanes.[4]The reaction produces fragments from the parent alkane, creating a diverse mixture of products; for instance,nitromethane,nitroethane,1-nitropropane,and2-nitropropaneare produced by treatingpropanewithnitric acidin the gas phase (e.g. 350–450 °C and 8–12atm).
- Nucleophilic substitutionreactions betweenhalocarbons[5]ororganosulfates[6]withsilveroralkalinitritesalts.
- Nitromethane can be produced in the laboratory by treatingsodium chloroacetatewithsodium nitrite.[7]
- Oxidationofoximes[8]orprimaryamines.[9]
- Reduction ofβ-nitro alcohols[10]ornitroalkenes.[11]
- Bydecarboxylationofα-nitrocarboxylic acidsformed fromnitrilesandethyl nitrate.[12][13]
Ter Meer Reaction
editInnucleophilic aliphatic substitution,sodium nitrite(NaNO2) replaces analkyl halide.In the so-called Ter Meer reaction (1876) named afterEdmund ter Meer,[14]the reactant is a 1,1-halonitroalkane:
Thereaction mechanismis proposed in which in the first slow step aprotonis abstracted from nitroalkane1to acarbanion2followed byprotonationto an aci-nitro3and finallynucleophilic displacementof chlorine based on an experimentally observed hydrogenkinetic isotope effectof 3.3.[15]When the same reactant is reacted withpotassium hydroxidethe reaction product is the 1,2-dinitro dimer.[16]
Occurrence
editIn nature
editChloramphenicolis a rare example of anaturally occurringnitro compound. At least some naturally occurring nitro groups arose by the oxidation of amino groups.[17]2-Nitrophenolis an aggregationpheromoneofticks.
Examples of nitro compounds are rare in nature.3-Nitropropionic acidfound infungiand plants (Indigofera).Nitropentadeceneis a defense compound found intermites.Aristolochic acidsare found in the flowering plant familyAristolochiaceae.Nitrophenylethane is found inAniba canelilla.[18]Nitrophenylethane is also found in members of theAnnonaceae,LauraceaeandPapaveraceae.[19]
In pharmaceuticals
editDespite the occasional use in pharmaceuticals, the nitro group is associated withmutagenicityandgenotoxicityand therefore is often regarded as a liability in thedrug discoveryprocess.[20]
Reactions
editNitro compounds participate in severalorganic reactions,the most important beingreduction of nitro compoundsto the corresponding amines:
- RNO2+ 3 H2→ RNH2+ 2 H2O
Virtually allaromatic amines(e.g.aniline) are derived from nitroaromatics through suchcatalytic hydrogenation.A variation is formation of a dimethylaminoarene withpalladium on carbonandformaldehyde:[21]
Theα-carbonof nitroalkanes is somewhat acidic. The pKavalues ofnitromethaneand2-nitropropaneare respectively 17.2 and 16.9 indimethyl sulfoxide(DMSO) solution, suggesting an aqueous pKaof around 11.[22]In other words, thesecarbon acidscan be deprotonated in aqueous solution. The conjugate base is called anitronate,and behaves similar to anenolate.In thenitroaldol reaction,itadds directlytoaldehydes,and, withenones,can serve as aMichael donor.Conversely, anitroalkenereacts with enols as a Michael acceptor.[23][24]Nitrosatinga nitronate gives anitrolic acid.[25]
Nitronates are also key intermediates in theNef reaction:when exposed to acids or oxidants, a nitronate hydrolyzes to acarbonylandazanone.[26]
Grignard reagentscombine with nitro compounds to give anitrone;but a Grignard reagent with an α hydrogen will then add again to the nitrone to give ahydroxylaminesalt.[27]
Dye syntheses
editTheLeimgruber–Batcho,BartoliandBaeyer–Emmerlingindole syntheses begin with aromatic nitro compounds.Indigocan be synthesized in a condensation reaction fromortho-nitrobenzaldehydeandacetonein strongly basic conditions in a reaction known as theBaeyer–Drewson indigo synthesis.
Biochemical reactions
editManyflavin-dependentenzymesare capable of oxidizing aliphatic nitro compounds to less-toxic aldehydes and ketones.Nitroalkane oxidaseand 3-nitropropionate oxidase oxidize aliphatic nitro compounds exclusively, whereas other enzymes such asglucose oxidasehave other physiological substrates.[28]
Explosions
editExplosive 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 molecularnitrogen(N2), carbon dioxide, and water. The explosive power of this redox reaction is enhanced because these stable products are gases at mild temperatures. Manycontact explosivescontain the nitro group.
See also
edit- Functional group
- Reduction of nitro compounds
- Nitration
- Nitrite(also an NO2group, but bonds differently)
- Nitroalkene
- Nitroglycerin
References
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