Chapter 22: Amines

Electrophilic Aromatic Substitution of Aryl Amines Summary

• Arylamines are potentially very reactive towards electrophilic aromatic substitution
• This is because -NH₂, -NHR2 and -NR2  are very strong activators and are ortho, para-directing.
• However the basicity of the amino group means it is unsuitable for reactions with acids (e.g. H₂SO₄ or AlCl₃) such as nitration, sulfonation and Friedel-Crafts alkylation or acylation.
• Polysubstitution can also be a problem. For example, bromination is very rapid, even in the absence of a catalyst, leading to bromination in all available ortho- and para- positions:

• To avoid these problems, it is customary to "protect" aryl amines by converting them to their N-acyl derivatives i.e. amides.
• The protecting group (an amide) can later be removed by either acid or base hydrolysis.

• The amide is a less powerful activating group than the simple amino group, -NH₂ since resonance within the N-acetyl group of the amide (see below) competes with delocalisation of the N lone pair into the ring.
• Steric effects in the amide also often lead to a decrease in the amount of the ortho-products.
• In principle, the sequence protect - substitute - deprotect is equivalent to being able to substitute the aniline directly.

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© Dr. Ian Hunt, Department of Chemistry