Friedel-Crafts Reaction

What Friedel-Crafts does

Both flavors of the reaction follow the standard electrophilic-aromatic-substitution playbook:

1. Generate a strong electrophile. A Lewis acid (AlCl₃, FeCl₃) strips a halide from RCl (alkylation) or RC(=O)Cl (acylation), unmasking R⁺ or R-C≡O⁺.
2. The arene attacks. The π electrons of benzene swing onto the cation, breaking aromaticity and forming an arenium ion (a cyclohexadienyl cation, also called the σ-complex).
3. Deprotonate. A base — usually AlCl₄⁻ — pulls off the proton from the sp³ carbon, restoring aromaticity and regenerating the catalyst.

    Ph-H  +  R-Cl  ──AlCl₃──→  Ph-R  +  HCl

  step 1:  R-Cl  +  AlCl₃  →  R⁺  +  AlCl₄⁻
  step 2:  Ph-H  +  R⁺   →  [arenium ion: H and R on same sp³ carbon]
  step 3:  arenium  +  AlCl₄⁻  →  Ph-R  +  HCl  +  AlCl₃

Acylation differs only in step 1: AlCl₃ pulls Cl⁻ off RC(=O)Cl to give an acylium ion R-C≡O⁺, which is resonance-stabilized between R-C≡O⁺ and R-C⁺=O. This stability is the reason acylation is so well-behaved relative to alkylation.

Worked example: benzene + acetyl chloride

Make acetophenone, the workhorse aryl methyl ketone, by Friedel-Crafts acylation.

    PhH  +  CH₃-C(=O)-Cl  ──AlCl₃ (1.1 eq), CS₂, 0→25 °C, 2 h──→  Ph-C(=O)-CH₃

• Reagents. Benzene (solvent and reactant, large excess), acetyl chloride 1.0 equiv, AlCl₃ 1.1 equiv (slightly super-stoichiometric — the product complexes one equivalent of AlCl₃).
• Conditions. Carbon disulfide or dichloromethane, 0 °C addition then warm to 25 °C, 2-3 h.
• Workup. Quench cautiously with ice/HCl(aq), extract, wash with NaHCO₃, distill.
• Yield. 85-95% acetophenone, monoacylated only — the deactivated product won't react again under these conditions.

Note that the AlCl₃ is technically stoichiometric, not catalytic, in any acylation: the product ketone coordinates aluminum so tightly that you need at least one equivalent to keep going. This is why "Lewis-acid-catalyzed" Friedel-Crafts is a slight misnomer for acylations, even though the Lewis acid is regenerated as a free species in the alkylation flavor.

Alkylation vs Acylation

	Friedel-Crafts alkylation	Friedel-Crafts acylation
Electrophile	R⁺ (free or tight ion pair)	R-C≡O⁺ (resonance-stabilized acylium)
Reagent	RCl, RBr, ROH, alkene + H⁺	RC(=O)Cl, anhydride, RCOOH/H₃PO₄
Catalyst loading	Catalytic AlCl₃ (5-10 mol%)	Stoichiometric AlCl₃ (≥ 1.0 equiv)
Carbocation rearrangement	Yes — common with primary halides	No — acylium is stable, doesn't rearrange
Polysubstitution	Yes — alkyl group activates the ring	No — acyl group deactivates the ring
Product directing effect	o,p-directing (next reaction)	m-directing (next reaction)
Works on benzene?	Yes	Yes
Works on nitrobenzene?	No (deactivated)	No (deactivated)
Works on aniline?	No (NH₂ poisons AlCl₃)	No (acylates the nitrogen first)
Most common use	Cumene (isopropylbenzene) for phenol manufacture	Aryl ketones, drug synthesis intermediates

Real-world applications

• Cumene process (commercial phenol). Benzene + propene + solid acid catalyst (zeolite or H₃PO₄/SiO₂) gives cumene at ~90% selectivity. Cumene is then auto-oxidized and cleaved to phenol + acetone — the route that produces over 95% of the world's phenol (≈ 12 million tons/year).
• Commercial styrene. Friedel-Crafts ethylation of benzene gives ethylbenzene (≈ 30 million tons/year), which is then dehydrogenated over Fe₂O₃-K₂CO₃ at 600 °C to styrene — the monomer for polystyrene. Modern plants use solid-acid zeolites (ZSM-5) instead of AlCl₃, but the Friedel-Crafts mechanism is identical.
• Detergent alkylates. Linear alkylbenzenes (LAB) for biodegradable detergents come from Friedel-Crafts of benzene with C₁₀-C₁₃ olefins over a HF or zeolite catalyst. Worldwide production exceeds 3 million tons annually.
• Anthraquinone dye intermediates. Phthalic anhydride + benzene with AlCl₃ gives o-benzoylbenzoic acid, then cyclized with H₂SO₄ to anthraquinone — the parent of indigo carmine and alizarin dyes.
• Pharmaceuticals. Ibuprofen historically used a Friedel-Crafts acetylation of isobutylbenzene to install the C(=O)CH₃ group; modern routes (BHC process, 1992) replaced AlCl₃ with HF then a Pd-catalyzed carbonylation to cut waste.

Pitfall: alkylation rearrangements

Try to make n-propylbenzene from benzene + 1-chloropropane / AlCl₃ and the major product is cumene (isopropylbenzene), not n-propylbenzene. The free n-propyl cation is primary and unstable; a 1,2-hydride shift converts it to the secondary isopropyl cation before it can attack the ring:

    CH₃CH₂CH₂-Cl  +  AlCl₃  →  CH₃CH₂CH₂⁺  (primary, unstable)
                                    |
                                    | 1,2-H shift
                                    v
                              (CH₃)₂CH⁺   (secondary, lower energy)
                                    +
                                  PhH
                                    ↓
                              Ph-CH(CH₃)₂   (cumene, ~80% of product mix)

The standard workaround: acylate first, reduce later. Use propanoyl chloride + AlCl₃ to install -C(=O)CH₂CH₃ (the propanoyl cation does not rearrange), then reduce the carbonyl to CH₂ with Clemmensen (Zn/Hg, HCl) or Wolff-Kishner (NH₂NH₂, KOH, hot ethylene glycol). The net result is clean n-propylbenzene in two steps from benzene.

Variants

• Friedel-Crafts with alkenes. Replace RCl with an alkene + a strong acid (HF, H₃PO₄, zeolite). Markovnikov protonation of the alkene gives the most stable cation, which then attacks the arene. Used industrially for cumene and ethylbenzene.
• Friedel-Crafts with alcohols. Protonate ROH to form ROH₂⁺, lose water to give R⁺. Convenient when the chloride is unavailable.
• Houben-Hoesch reaction. Acylation of activated arenes (phenols, polyhydroxyarenes) with a nitrile + HCl + ZnCl₂ — a Friedel-Crafts variant that delivers an iminium intermediate, hydrolyzed in workup to a ketone.
• Gattermann-Koch formylation. CO + HCl + AlCl₃ on benzene gives benzaldehyde (a "formyl" Friedel-Crafts) — a workaround for the fact that formyl chloride doesn't exist as a stable compound.
• Modern solid-acid catalysts. H-zeolites (ZSM-5, beta), heteropoly acids, sulfated zirconia. Recyclable, less corrosive, and avoid the chloride waste of AlCl₃.
• Asymmetric Friedel-Crafts. Chiral N,N′-dioxide-Sc(III) complexes or chiral phosphoric acids can drive enantioselective arylations of α,β-unsaturated ketones with electron-rich heterocycles (indoles, pyrroles).

Common pitfalls

• Aniline and pyrrole basicity. NH₂ groups complex AlCl₃ tightly, deactivating the catalyst and the ring. Protect amines as amides (acetanilide) before attempting Friedel-Crafts; the amide nitrogen is far less basic.
• Polyalkylation creep. Each alkyl group makes the ring more reactive. If you can't tolerate dialkyl side products, run with 5-10× excess benzene as solvent, or switch to acylation + reduction.
• Choice of solvent. CS₂ and CH₂Cl₂ are inert. Don't use ethers (Lewis bases that quench AlCl₃) or alcohols (protonate the catalyst).
• Moisture sensitivity. AlCl₃ hydrolyzes vigorously to Al(OH)₃ + HCl. Pre-dry glassware and reagents; quench by slow addition into ice water, never the other way.
• Choosing the wrong directing reference. The substituent that is already on the ring tells you where the new electrophile goes — alkyl groups are o,p-directors and ring-activators, acyl groups are m-directors and ring-deactivators. Plan multi-step syntheses with the eventual substitution pattern in mind.