Difficulty: Intermediate to Advanced | Prerequisites: EAS Core Concepts study notes (Doc 1 of this series), understanding of carbocation stability and rearrangements (Ch. 7–8).
Friedel–Crafts reactions are the main tools for forming new C–C bonds on aromatic rings, and multi-step synthesis problems are where the entire chapter comes together. This is the material that turns a list of individual reactions into a usable toolkit: you need to know not just what each reaction does, but in what order to apply them and what pitfalls to avoid. Exam synthesis questions typically start with benzene and ask for a product with two or three substituents in specific positions, requiring you to think backwards from the target.
Friedel–Crafts alkylation attaches alkyl groups but suffers from rearrangement and polyalkylation. Acylation followed by reduction is the clean alternative. Multi-step synthesis problems require you to choose the right order of reactions so each substituent's directing effect places the next group correctly.
Acylium ion (RCO+)
The resonance-stabilised electrophile in Friedel–Crafts acylation. Because the positive charge is shared between carbon and oxygen, acylium ions do not rearrange. Think of it as: the well-behaved version of a carbocation.
Carbocation rearrangement
A 1,2-hydride shift or 1,2-methyl shift that converts a less stable carbocation into a more stable one. In simple terms, the carbocation "jumps" to a neighbouring carbon if that gives it more stability, and this changes the product you get.
Polyalkylation
The tendency for Friedel–Crafts alkylation to keep going, because the first alkyl group activates the ring toward further reaction. Think of it as: the product is tastier to the electrophile than the starting material was.
Retrosynthetic analysis
Working backwards from the target molecule to benzene, identifying which bond to disconnect at each step and what reaction would form it. In simple terms, start with what you want, figure out what the last step must be, then work backwards to benzene.
Reagents: Alkyl halide (RCl, RBr) + Lewis acid catalyst (AlCl3, FeCl3).
Electrophile formed: A carbocation (R+), or a strongly polarised R–X---AlCl3 complex.
Mechanism: The Lewis acid abstracts the halide, generating the electrophile. The aromatic pi system attacks the carbocation. A base (often AlCl4−) removes the proton from the sigma complex to restore aromaticity.
Problems with alkylation:
Carbocation rearrangement: If a primary carbocation is generated, it will rearrange to a more stable secondary or tertiary carbocation via 1,2-hydride or 1,2-methyl shift. This means you cannot reliably install a primary alkyl group longer than methyl by direct alkylation.
Polyalkylation: The alkyl group you just added is an activating group, so the product ring is more reactive than the starting benzene. Under standard conditions, multiple alkyl groups will be added. Controlling for monoalkylation requires a large excess of benzene.
Does not work on deactivated rings: Rings bearing –NO2, –COR, –SO3H, –CN, and similar groups are too electron-poor for Friedel–Crafts conditions. Aniline (–NH2) also fails, not because the ring is deactivated, but because the amine coordinates with AlCl3, effectively tying up the catalyst.
Reagents: Acyl chloride (RCOCl) + AlCl3 (more than one equivalent needed, as AlCl3 coordinates with the product ketone).
Electrophile formed: Acylium ion (RCO+), stabilised by resonance between C=O+ and C≡O.
Advantages over alkylation:
No rearrangement (the acylium ion is resonance-stabilised and does not need to shift).
No polyacylation (the product ketone is a deactivating group, so the ring becomes less reactive after the first acylation, preventing a second reaction).
When you need to install a straight-chain alkyl group (e.g. an n-propyl group on benzene):
Acylate with the corresponding acyl chloride (propanoyl chloride / AlCl3) to get the aryl ketone.
Reduce the carbonyl to CH2 using Clemmensen reduction (Zn/Hg, HCl) or Wolff–Kishner reduction (NH2NH2, KOH, heat).
This two-step route gives you the product that direct alkylation cannot deliver cleanly.
Methyl or tert-butyl group needed: Direct alkylation is fine (methyl cannot rearrange; tert-butyl is already tertiary).
Isopropyl group needed: Direct alkylation works (the secondary carbocation is the desired one).
Primary alkyl group (ethyl, n-propyl, n-butyl, etc.) or any case where rearrangement would give the wrong product: Use acylation–reduction.
Question 18.8 from the problem set tests exactly this decision for each structure shown.
Look at the target molecule and ask: what was the last reaction? What did the ring look like before that step? Keep working backwards until you reach benzene.
Identify the relationship between substituents. Are they ortho, meta, or para to each other? This tells you what directing effect you need from the first group installed.
Install the group that directs correctly first. If you need two groups that are meta to each other, install a meta director first. If you need groups that are ortho/para, install an ortho/para director first.
Remember that some groups can be converted. –NO2 can be reduced to –NH2 (Zn/HCl or H2/Pd). An aryl ketone (from acylation) can be reduced to an alkyl group (Clemmensen). This means the group you install for its directing effect does not have to be the group in the final product.
Check Friedel–Crafts compatibility. If your plan involves a Friedel–Crafts step on a ring that already carries –NO2 or another strong deactivator, that step will fail. Rearrange the order.
Consider blocking groups. If an ortho/para director is present and you want substitution at only one of those positions, use a sulfonic acid group (–SO3H) as a removable blocker at the position you want to protect, carry out the desired EAS, then remove the blocker with dilute acid.
Para-bromonitrobenzene from benzene: Nitrate first (–NO2 is meta director), then brominate. Br enters meta to NO2, which is the same as para if you number from the other direction, but be careful: –NO2 directs meta, so Br goes meta to NO2. To get the para relationship, brominate first (–Br directs ortho/para), then nitrate (–NO2 goes ortho or para to Br; para major).
Meta-substituted anilines: Install –NO2 first (meta director), carry out the second EAS, then reduce –NO2 to –NH2. You cannot use –NH2 as a directing group for meta substitution because –NH2 is an ortho/para director.
Ortho or para with control: Use acylation (the product ketone is a meta director, but that is the acyl group's effect), or use a blocking group to prevent one of the two ortho/para positions from reacting.
Target: H2N–C6H4–Br (para relationship).
Reasoning: –NH2 is ortho/para directing, but if you install it first (via nitration then reduction), the –NH2 will coordinate with AlCl3 and block Friedel–Crafts, and halogenation of aniline is hard to control (trisubstitution). Strategy: nitrate first, brominate, then reduce.
Route: Benzene → nitration (HNO3/H2SO4) → nitrobenzene → bromination (Br2/FeBr3; –NO2 is meta director, so Br enters meta to NO2, but wait, we need para-bromoaniline, meaning Br and NH2 are para). Re-think: Brominate benzene first (Br2/FeBr3 → bromobenzene), then nitrate (HNO3/H2SO4; –Br is ortho/para director → major product is para-bromonitrobenzene), then reduce –NO2 to –NH2 (Zn/HCl or H2/Pd).
Flaw: Step 1 installs –NO2 (a strong deactivator). Friedel–Crafts alkylation in Step 2 will not proceed on the deactivated ring.
Fix: Alkylate first (EtCl/AlCl3 → ethylbenzene), then nitrate. –CH2CH3 is an ortho/para director, so –NO2 enters the para position (major product).
The PDF shows a structure with a branched arrangement on the ring. If the required product has a carbon skeleton that would demand a primary carbocation, neither direct alkylation (rearrangement) nor acylation (gives a ketone, not the correct skeleton) can deliver it. In such cases, the problem is testing whether you recognise the limitation.
Always check three things before writing your synthesis:
Does the order of reactions match the directing effects needed?
Are there any Friedel–Crafts compatibility issues (deactivated ring, amine coordination)?
Would carbocation rearrangement occur in any alkylation step?
"Acylation is just another form of alkylation." They are mechanistically related, but the outcomes differ sharply. Acylation does not rearrange, does not polysubstitute, and the product is a ketone (deactivated ring), not an alkane side chain. Treating them as interchangeable on an exam will cost marks.
"You can do Friedel–Crafts on any aromatic ring." You cannot. Strongly deactivated rings (–NO2, –CN, –SO3H) and amines (which tie up the Lewis acid catalyst) are off-limits.
"The order of steps in a synthesis doesn't matter as long as you use the right reagents." It matters enormously. Each group you add changes the ring's reactivity and directing effects, so the same two reactions in different order give different products.
⚠️ "Design a synthesis from benzene" is the signature exam question for this chapter. Expect at least one.
⚠️ Identifying flawed syntheses (as in Problem 18.54) is a common exam format: you are given a proposed route and must find the error.
⚠️ Know the acylation–reduction workaround cold. If an exam question presents a straight-chain alkyl group on a ring, the expected answer is almost always acylation + Clemmensen.
⚠️ The blocking group strategy (sulfonation/desulfonation) is tested less frequently but is high-value when it appears, because most students forget it.
Q: Starting from benzene, propose a synthesis of meta-chloronitrobenzene.
A: Chlorinate first (Cl2/AlCl3 → chlorobenzene). Then nitrate (HNO3/H2SO4). –Cl is an ortho/para director, so you would get ortho and para products, not meta. Re-think: Nitrate first (HNO3/H2SO4 → nitrobenzene). Then chlorinate (Cl2/AlCl3). –NO2 is a meta director, so –Cl enters the meta position. This is the correct route.
Q: Why does Friedel–Crafts acylation not suffer from polyacylation?
A: The acyl group installed in the first reaction is a deactivating group (electron-withdrawing through the carbonyl). The product ring is therefore less reactive than benzene, and a second acylation is strongly disfavoured under standard conditions.
Q: Benzene is treated with 2-methylpropene and sulfuric acid (Problem 18.48). The product is tert-butylbenzene. Propose a mechanism.
A: Sulfuric acid protonates 2-methylpropene, and the proton adds to the less substituted carbon (Markovnikov's rule), generating a tertiary carbocation. This tert-butyl cation is the electrophile. It attacks the benzene ring to form the sigma complex, and loss of a proton restores aromaticity, giving tert-butylbenzene.
Q: Identify the flaw in this synthesis: benzene → (1) Br2/FeBr3, (2) CH2Cl2 (0.5 equiv)/AlCl3 → target is diphenylmethane.
A: The first step is fine (gives bromobenzene). The second step uses methylene chloride with AlCl3 to try to bridge two rings, but bromobenzene is deactivated relative to benzene (–Br is weakly deactivating), and the real issue is whether the conditions generate a viable electrophile from CH2Cl2. This reaction can give diphenylmethane if benzene (not bromobenzene) is used, because AlCl3 can generate a chloromethyl cation which attacks one ring, then the resulting benzyl chloride attacks a second ring.
Friedel–Crafts reactions connect to carbocation chemistry (Ch. 7–8): the same rearrangements that govern SN1 products appear here. The acylation–reduction pathway connects to carbonyl chemistry (ketone reduction, Ch. 20). Multi-step synthesis planning is the precursor to retrosynthetic analysis in advanced organic chemistry courses. The blocking group strategy reappears when you study diazonium chemistry (Ch. 25), where –SO3H can protect a position during diazotisation.
Friedel-Crafts alkylation, Friedel-Crafts acylation, Lewis acid catalyst, AlCl3, acylium ion, carbocation rearrangement, 1 2 hydride shift, 1 2 methyl shift, polyalkylation, Clemmensen reduction, Wolff-Kishner reduction, retrosynthetic analysis, blocking group, sulfonation desulfonation, multi-step synthesis benzene, aromatic synthesis strategy, order of reactions EAS, organic chemistry chapter 18, NYU chemistry