Nitration
Encyclopedia
Nitration is a general chemical process
for the introduction of a nitro group
into a chemical compound
. The dominant application of nitration is for the production of nitrobenzene, the precursor to methylene diphenyl diisocyanate
. Nitrations are famously used for the production of explosives, for example the conversion of glycerin to nitroglycerin and the conversion of toluene
to trinitrotoluene. Millions of tons of nitroaromatics are produced annually.
and sulfuric acid
, so-called "mixed acid.". This mixture produces the nitronium ion
(NO2+), which is the active species in aromatic nitration. This active ingredient, which can be isolated in the case of nitronium tetrafluoroborate
, also effects nitration without the need for the mixed acid. The 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 50 °C. The process is one example of electrophilic aromatic substitution
, which involve the attack of the electron-rich benzene
ring:
Alternative mechanisms have also been proposed, including one involving single electron transfer (SET).
can be selective trinitrated or tetranitrated. Another example of trinitration can be found in the synthesis of phloroglucinol
.
The substituents on aromatic rings affect the rate
of this electrophilic aromatic substitution
. Deactivating groups such as other nitro
groups have an electron-withdrawing effect. Such groups deactivate (slow) the reaction and directs the electrophilic nitronium ion to attack the aromatic meta position. Deactivating meta-directoring substituents include sulfonyl
, cyano groups, keto
, ester
s, and carboxylates. Nitration can be accelerated by activating group
s such as amino, hydroxy
and methyl groups also amide
s and ether
s resulting in para and ortho isomers.
The direct nitration of aniline
with nitric acid and sulfuric acid, according to one source results in a 50/50 mixture of para and meta nitroaniline. In this reaction the fast-reacting and activating aniline (ArNH2) exists in equilibrium with the more abundant but less reactive (deactivated) anilinium ion (ArNH3+), which may explain this reaction product distribution. According to another source 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 nitroamide back to the nitroamine.
In the Wolfenstein-Boters reaction, benzene
reacts with nitric acid and mercury nitrate to give picric acid
.
s and nonaflates ipso substitution can take place as well in so-called ipso nitration. The phrase was first used by Perrin and Skinner in 1971 in an investigation into chloroanisole nitration In one protocol 4-chloro-n-butylbenzene is reacted with sodium nitrite
in t-butanol in presence of 0.5 mol% Pd2(dba)3
,a biarylphosphine ligand and a phase-transfer catalyst to 4-nitro-n-butylbenzene
Chemical process
In a "scientific" sense, a chemical process is a method or means of somehow changing one or more chemicals or chemical compounds. Such a chemical process can occur by itself or be caused by somebody. Such a chemical process commonly involves a chemical reaction of some sort...
for the introduction of a nitro group
Nitro compound
Nitro compounds are organic compounds that contain one or more nitro functional groups . They are often highly explosive, especially when the compound contains more than one nitro group and is impure. The nitro group is one of the most common explosophores used globally...
into a chemical compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
. The dominant application of nitration is for the production of nitrobenzene, the precursor to methylene diphenyl diisocyanate
Methylene diphenyl diisocyanate
Methylene diphenyl diisocyanate, most often abbreviated as MDI, is an aromatic diisocyanate. It exists in three isomers, 2,2'-MDI, 2,4'-MDI, and 4,4'-MDI, but the 4,4' isomer is most widely used. This isomer is also known as Pure MDI. MDI reacts with polyols in the manufacture of polyurethane...
. Nitrations are famously used for the production of explosives, for example the conversion of glycerin to nitroglycerin and the conversion of toluene
Toluene
Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic...
to trinitrotoluene. Millions of tons of nitroaromatics are produced annually.
Aromatic nitration
Typical nitrations use nitric acidNitric acid
Nitric acid , also known as aqua fortis and spirit of nitre, is a highly corrosive and toxic strong acid.Colorless when pure, older samples tend to acquire a yellow cast due to the accumulation of oxides of nitrogen. If the solution contains more than 86% nitric acid, it is referred to as fuming...
and sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
, so-called "mixed acid.". This mixture produces the nitronium ion
Nitronium ion
The nitronium ion, or sometimes the nitryl ion , , is a generally reactive cation created by the removal of an electron from the paramagnetic nitrogen dioxide molecule, or the protonation of nitric acid....
(NO2+), which is the active species in aromatic nitration. This active ingredient, which can be isolated in the case of nitronium tetrafluoroborate
Nitronium tetrafluoroborate
Nitronium tetrafluoroborate is an inorganic compound with formula NO2BF4. It is a salt of nitronium cation and tetrafluoroborate anion. It is a colorless crystalline solid, which reacts heavily with water to form the corrosive acids HF and HNO3. As such, it must be handled under water-free conditions...
, also effects nitration without the need for the mixed acid. The 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 50 °C. The process is one example of electrophilic aromatic substitution
Electrophilic aromatic substitution
Electrophilic aromatic substitution EAS is an organic reaction in which an atom, usually hydrogen, appended to an aromatic system is replaced by an electrophile...
, which involve the attack of the electron-rich benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
ring:
Alternative mechanisms have also been proposed, including one involving single electron transfer (SET).
Scope
Selectivity can be a challenge in nitrations. Depending on conditions, fluorenoneFluorenone
Fluorenone is an aromatic organic compound with the chemical formula C13H8O. It is used to make antimalaria drugs.It can be produced from fluorene via oxidation ....
can be selective trinitrated or tetranitrated. Another example of trinitration can be found in the synthesis of phloroglucinol
Phloroglucinol
Phloroglucinol is a benzenetriol. It is an organic compound that is used in the synthesis of pharmaceuticals and explosives. This molecule exists in two forms, or tautomers, 1,3,5-trihydroxybenzene, which has phenol-like, and 1,3,5-cyclohexanetrione , which has ketone-like character. These two...
.
The substituents on aromatic rings affect the rate
Reaction rate
The reaction rate or speed of reaction for a reactant or product in a particular reaction is intuitively defined as how fast or slow a reaction takes place...
of this electrophilic aromatic substitution
Electrophilic aromatic substitution
Electrophilic aromatic substitution EAS is an organic reaction in which an atom, usually hydrogen, appended to an aromatic system is replaced by an electrophile...
. Deactivating groups such as other nitro
Nitro
-Chemistry:*Nitroglycerin, an explosive chemical compound*Nitromethane, the simplest organic nitro compound; also used to fuel high-performance internal-combustion engines*Nitrous oxide, "laughing gas", used in some dental procedures as an anaesthetic...
groups have an electron-withdrawing effect. Such groups deactivate (slow) the reaction and directs the electrophilic nitronium ion to attack the aromatic meta position. Deactivating meta-directoring substituents include sulfonyl
Sulfonyl
A sulfonyl group can refer either to a functional group found primarily in sulfones or to a substituent obtained from a sulfonic acid by the removal of the hydroxyl group similarly to acyl groups...
, cyano groups, keto
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
, ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
s, and carboxylates. Nitration can be accelerated by activating group
Activating group
In organic chemistry, a functional group is called an activating group if a benzene molecule to which it is attached more readily participates in electrophilic substitution reactions...
s such as amino, hydroxy
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
and methyl groups also amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
s and ether
Ether
Ethers are a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R'. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
s resulting in para and ortho isomers.
The direct nitration of aniline
Aniline
Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the prototypical aromatic amine. Being a precursor to many industrial chemicals, its main use is in the manufacture of precursors to polyurethane...
with nitric acid and sulfuric acid, according to one source results in a 50/50 mixture of para and meta nitroaniline. In this reaction the fast-reacting and activating aniline (ArNH2) exists in equilibrium with the more abundant but less reactive (deactivated) anilinium ion (ArNH3+), which may explain this reaction product distribution. According to another source a more controlled nitration of aniline starts with the formation of acetanilide by reaction with acetic anhydride
Acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
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 nitroamide back to the nitroamine.
In the Wolfenstein-Boters reaction, benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
reacts with nitric acid and mercury nitrate to give picric acid
Picric acid
Picric acid is the chemical compound formally called 2,4,6-trinitrophenol . This yellow crystalline solid is one of the most acidic phenols. Like other highly nitrated compounds such as TNT, picric acid is an explosive...
.
Ipso nitration
With aryl chlorides, triflateTriflate
Trifluoromethanesulfonate, also known by the trivial name triflate, is a functional group with the formula CF3SO3-. The triflate group is often represented by -OTf, as opposed to -Tf...
s and nonaflates ipso substitution can take place as well in so-called ipso nitration. The phrase was first used by Perrin and Skinner in 1971 in an investigation into chloroanisole nitration In one protocol 4-chloro-n-butylbenzene is reacted with sodium nitrite
Sodium nitrite
Sodium nitrite is the inorganic compound with the chemical formula NaNO2. It is a white to slight yellowish crystalline powder that is very soluble in water and is hygroscopic...
in t-butanol in presence of 0.5 mol% Pd2(dba)3
Tris(dibenzylideneacetone)dipalladium(0)
Trisdipalladium or Pd23 is an organometallic complex based on palladium and dibenzylideneacetone used in organic chemistry. It was discovered in 1970.-Preparation and structure:...
,a biarylphosphine ligand and a phase-transfer catalyst to 4-nitro-n-butylbenzene