Chemistry of Benzene Substituents | Organic Chemistry 3

The chemistry of benzene substituents is studied in this chapter: reactivity of methylbenzene or toluene, benzylic oxidations and reductions, nucleophilic aromatic substitutions, properties and reactivity of phenol, Claisen rearrangement, arenediazonium salts

Reactivity of Methylbenzene

Benzylic radicals, cations and anions are stabilized by resonance with the benzene ring

Consequences:

⇒ relatively easy radical halogenations
SN1 and SN2 reactions
⇒ benzylic anion formation: H of the methyl substituent are slightly acidic (pKa = 41)

 

 

Reactivity of methylbenzene (or toluene):

Radical halogenation:

Mechanism:

Radical process via an initiation step to activate Br2 then propagation steps
 

Substitution nucleophilic:

Mechanism:

SN1 and SN2 reactions, the benzylic cation being a good electrophile
 

Deprotonation reaction:

A strong base as BuLi is needed

Benzylic Oxidation and Reduction

Oxidation:


Selective oxidation of a benzylic alcohol:

 

Reduction:


A benzylic substituent can be used as a protecting group for the hydroxy function

Nucleophilic Aromatic Substitution

Mechanism:

Addition-elimination. Nucleophilic attack will occur at the ipso position of 2 electron withdrawing substituents

 

Aromatic Substitution through benzyne intermediate:
 

Mechanism:

Elimination-addition

Properties and Reactivity of Phenol

There is a keto-enol equilibrium with phenol. The enol form is favored by aromaticity
The proton of the hydroxy function is acidic because the corresponding anion is stabilized by resonance


Reactivity of phenol:

- Electrophilic Aromatic Substitution
- SN reactions with the phenoxide ion:

Claisen Rearrangement

Mechanism:

Concerted reaction involving the movement of 6 electrons

 

Aliphatic Claisen rearrangement:

Arenediazonium Salts

Stabilized by resonance:
 

 

Synthesis:

 

Reactivity:

- Hydrolysis:​​​​​

- Sandmeyer reaction:

with Nu = Nucleophile (Cl, Br, CN ...)

 

- Diazo coupling with strongly activated benzene: