Nitration

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 tomethylene 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.

Aromatic nitration

Typical nitrations use nitric acid 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-richbenzene ring:

Nitration Process

Scope
Selectivity can be a challenge in nitrations. Depending on conditions, fluorenone can be selective trinitrated or tetranitrated. Another example of trinitration can be found in the synthesis ofphloroglucinol. 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, esters, andcarboxylates. Nitration can be accelerated by activating groups such as amino, hydroxy and methyl groups also amides and ethers resulting in para and ortho isomers.

Ipso Nitration
With aryl chlorides, triflates and nonaflates ipso substitution can take place as well in socalled ipso nitration. The phrase was first used by Perrin and Skinner in 1971 in an investigation into chloroanisole nitration .In one protocol 4-chloron-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 to4-nitro-nbutylbenzene.

Example of Ipso Nitration

The nitration of methylbenzene (toluene)

Methylbenzene reacts rather faster than benzene - in nitration, the reaction is about 25 times faster. That means that you would use a lower temperature to prevent more than one nitro group being substituted - in this case, 30C rather than 50C. Apart from that, the reaction is just the same using the same nitrating mixture of concentrated sulphuric and nitric acids. You get a mixture of mainly two isomers formed: 2nitromethylbenzene and 4-nitromethylbenzene. Only about 5% of the product is 3-nitromethylbenzene. Methyl groups are said to be2,4-directing.

 Just as with benzene, will get a certain amount of dinitro compound formed under the conditions of the reaction, but virtually no trinitro product because the reactivity of the ring decreases for every nitro group added. From an experimental point of view this is just as well. Trinitromethylbenzene used to be called trinitrotoluene or TNT! The reason for the 2,4-directing effect of the methyl group is beyond UK A level, but the increased reaction rate can be explained up to a point. The reactivity of a benzene ring is governed by the electron density around the ring. Methyl groups tend to "push" electrons towards the ring - increasing the density, and so making the ring more attractive to attacking reagents.

 This is actually a simplification. In order to understand the rate effect properly you have to think about the stability of the intermediate ions formed during the reactions, because this affects the activation energy of the reactions. This is also the basis for the directing effect and is again beyond UK A level.