Chapter 7 Summary & Comparison Tables

Amines and amides feed directly into electrophilic aromatic substitution (EAS) chemistry via activation (–NR₂/–NH₂/–OH) or deactivation (–C=O, –NO₂). Use these patterns to predict orientation and relative rates.

Aromatic Electrophilic Substitution at a Glance

• Nitration: HNO₃ + H₂SO₄ → NO₂⁺; gives Ar–NO₂.
• Sulfonation: fuming H₂SO₄ (H₂SO₄ + SO₃) → Ar–SO₃H; reversible (desulfonation in hot dilute acid).
• Halogenation: X₂ + FeX₃ (or AlCl₃) → Ar–X; Cl/Br straightforward, I₂ needs oxidant.
• Friedel–Crafts alkylation: R–Cl + AlCl₃ → Ar–R; watch for carbocation rearrangements and polyalkylation; fails on strongly deactivated rings or amines (amines complex AlCl₃).
• Friedel–Crafts acylation: RCOCl + AlCl₃ → Ar–COR; no rearrangements, product less activating so usually mono-acylation; fails on strongly deactivated rings.

Directing Effects and Reactivity

• Ortho/para directors (activating): Lone-pair donors (–NH₂/–NHR/–NR₂, –OH/–OR, amides/esters like –NHCOCH₃, –OCOR) and weakly activating alkyl/aryl (–R, –Ph). They speed EAS and direct o/p.
• Meta directors (deactivating): Strong withdrawers (–NO₂, –C≡N, carbonyls –CHO/–COR/–COOR/–COOH, –SO₃H, –NR₃⁺) slow EAS and direct meta.
• Halogens: Deactivating overall (–I) but o/p-directing because lone pairs can stabilize the sigma complex by resonance. Reactions are slower and need stronger conditions.
• Relative rates (nitration example): phenol (fast, o/p) > toluene (o/p) > benzene ≈ bromobenzene (o/p but slower) > nitrobenzene (very slow, meta).

Substituent Effects Comparison

Substituent	Activation/Deactivation	Directing	Comments
–NH₂, –NHR, –NR₂	Strongly activating	Ortho/Para	Lone-pair donation; prone to polysubstitution; protonated in strong acid.
–OH, –O⁻	Strongly activating	Ortho/Para	Lone-pair donation; inductive withdrawal partly offsets but resonance dominates.
–NHC(O)R, –OC(O)R	Moderately activating	Ortho/Para	Lone pair can donate but also delocalized into C=O.
–R (alkyl/aryl)	Weakly activating	Ortho/Para	Hyperconjugation/induction; stabilizes o/p sigma complexes slightly.
–F, –Cl, –Br, –I	Deactivating	Ortho/Para	−I slows reaction, but resonance donation directs o/p; para often major.
–C≡N	Strongly deactivating	Meta	Withdraws by resonance and induction.
–NO₂	Strongly deactivating	Meta	Powerful −M/−I; o/p sigma complexes especially unstable.
–C(=O)R (CHO, COR, COOH, COOR)	Strongly deactivating	Meta	Carbonyl withdraws electron density; o/p attack destabilized.
–SO₃H	Strongly deactivating	Meta	Sulfonyl withdraws strongly; reaction is reversible.
–NR₃⁺	Strongly deactivating	Meta	Strong inductive withdrawal; no resonance donation possible.

Multiple Substituents and Strategy

• The more activating substituent usually dominates orientation; conflicting directives can give mixtures or require blocking/protection.
• Strongly deactivated rings may need forcing conditions or may fail (e.g., heavily nitro-substituted).
• Para selectivity can be improved by blocking ortho (temporary sulfonation) or by protecting an –OH as an acyl group to reduce activation and add steric bulk.

Key Takeaways

• Classify substituents quickly: most activators (except halogens) are o/p; most deactivators (except halogens) are meta.
• Use sulfonation/desulfonation or protection to control orientation when strong activators drive ortho products.
• Remember halogens are the exception: slow but o/p-directing.
• Diazonium and amine chemistry plug into this map: amines strongly activate; diazonium formation/deactivation steps can be used to tune directing and introduce substituents.