To brominate phenol, all we had to do was to mix bromine and phenol—if we do this with benzene itself, nothing happens. We therefore say that, relative to benzene, the OH group in phenol activates the ring towards electrophilic attack. The OH group is both activating and ortho, para-directing. Other groups that can donate electrons also activate and direct ortho, para. Anisole (methoxybenzene) is the ‘enol ether’ equivalent of phenol. It reacts faster than benzene with electrophiles.

2,4-D The multiple chlorination of another oxygen-substituted compound, phenoxyacetic acid, leads to a useful product. Chlorination with two equivalents of chlorine provides 2,4-dichlorophenoxy acetic acid, which is the herbicide 2,4-D. The oxygen substituent again activates the ring and directs the chlorination to the ortho and para positions.

Nitration of phenol is also very fast and can be problematic under the usual nitration conditions (conc. HNO3, conc. H2SO4) because concentrated nitric acid oxidizes phenols. The solution is to use dilute nitric acid. The concentration of NO₂ + will be small but that does not matter with such a reactive benzene ring.

The product is a mixture of ortho- and para-nitrophenol from which the ortho compound can be separated by steam distillation. A strong intramolecular hydrogen bond reduces the availability of the OH group for intermolecular hydrogen bonding so the ortho compound has a lower boiling point.

Paracetamol from a phenol The remaining para-nitrophenol is used in the manufacture of the painkiller paracetamol (also known as acetaminophen).

The phenoxide ion is even more reactive towards electrophilic attack than phenol. It man ages to react with such weak electrophiles as carbon dioxide. This reaction, known as the Kolbe–Schmitt process, is used industrially to prepare salicylic acid (2-hydroxybenzoic acid), a precursor in making aspirin.

The O⁻ substituent is ortho, para-directing but the electrophilic substitution step with CO₂ gives mostly the ortho product. There must be some coordination between the sodium ion and the oxygen atoms of both the phenoxide and CO₂ that delivers the electrophile to the ortho position.

مواضيع ذات صلة

The addition–elimination mechanism

Nucleophilic aromatic substitution

Nucleophilic epoxidation

Conjugate substitution reactions

Unsaturated nitriles and nitro compounds

Promoting conjugate addition with copper(I) salts

Structural factors

Halogens show evidence of both electron withdrawal and donation

Some substituents withdraw electrons by conjugation

Electron-withdrawing substituents give meta products

The sulfonation of toluene

Selectivity between ortho and para positions