Source: Organic Chemistry, The Ohio State University
Tags: halogenation, nitration, sulfonation, Friedel-Crafts acylation, Friedel-Crafts alkylation, acylium ion, carbocation rearrangement, Clemmensen reduction, Wolff-Kishner reduction, Lewis acid, benzene reactions
Difficulty: Intermediate Prerequisites: Part 1 of these notes (EAS Mechanism Fundamentals). Familiarity with Lewis acids, carbocation rearrangements (hydride and methyl shifts), and basic carbonyl chemistry.
Once you understand the three-step EAS framework (generate electrophile, attack, restore aromaticity), each named reaction is just a variation with a different electrophile. This set of notes covers the five classic EAS reactions: halogenation, nitration, sulfonation, Friedel-Crafts acylation, and Friedel-Crafts alkylation. Each has its own reagents and quirks, but the underlying logic is identical. Knowing the electrophile for each reaction, how it is generated, and the practical limitations of each method is essential for both exam problems and multi-step synthesis planning.
The five main EAS reactions differ only in the electrophile used. Halogenation uses X2 with a Lewis acid, nitration uses the nitronium ion (NO2+) from mixed acids, sulfonation uses SO3 from fuming sulfuric acid, and the two Friedel-Crafts reactions use acylium ions or carbocations generated with AlCl3. Each follows the same three-step mechanism, but sulfonation is uniquely reversible, and Friedel-Crafts alkylation has pitfalls (over-alkylation, rearrangement) that acylation avoids.
Nitronium ion (NO2+)
The electrophile in aromatic nitration, generated by protonation of nitric acid with sulfuric acid followed by loss of water. It is isoelectronic with CO2 (linear, 16 valence electrons). Think of it as: the stripped-down, positively charged core of nitric acid that attacks the ring.
Acylium ion (RCO+)
A resonance-stabilised carbocation formed when an acyl chloride reacts with AlCl3. The positive charge is shared between carbon and oxygen. In simple terms, it is the electrophile in Friedel-Crafts acylation, and because it is stabilised by the oxygen, it does not rearrange.
Friedel-Crafts acylation
An EAS reaction that places an acyl group (RCO) on the aromatic ring, using an acyl chloride and AlCl3. The product is an aryl ketone.
Friedel-Crafts alkylation
An EAS reaction that places an alkyl group on the ring, using an alkyl halide (or alkene or alcohol) with a Lewis acid to generate a carbocation electrophile.
Clemmensen reduction
Reduction of a carbonyl group to a CH2 using zinc amalgam (Zn/Hg) in HCl. Used to convert a Friedel-Crafts acylation product to the equivalent alkylbenzene without rearrangement.
Wolff-Kishner reduction
Reduction of a carbonyl to a CH2 using hydrazine (H2NNH2) followed by KOH and heat. An alternative to Clemmensen reduction under basic rather than acidic conditions.
Desulfonation
The reverse of sulfonation, favoured in hot, dilute aqueous acid. Sulfonation is the only common EAS reaction that is readily reversible.
Reagents and catalysts:
Bromination: Br2 / FeBr3
Chlorination: Cl2 / FeCl3
Iodination: I2 / CuCl2 or I2 / H2O2 (iodination requires a different oxidant because I2 alone is too weak an electrophile even with a standard Lewis acid)
Mechanism follows the standard three steps. The Lewis acid polarises the dihalogen, creating an electrophilic halogen that the ring attacks.
Product: a monohalobenzene (e.g. bromobenzene, chlorobenzene, iodobenzene).
Reagents: HNO3 + H2SO4 (mixed acid).
Electrophile generation: sulfuric acid protonates nitric acid, which loses water to form NO2+.
HNO3 + H2SO4 → NO2+ + HSO4 minus + H2O
NO2+ is isoelectronic with CO2: linear geometry with a formal positive charge on nitrogen.
The ring attacks NO2+, forming an arenium ion. Water (or HSO4 minus) acts as the base that removes the proton in the final step, producing nitrobenzene and H3O+.
Alternative reagents: pure sources of NO2+ such as the NO2+ BF4 minus salt can be used directly.
Synthetic utility: nitro groups are easily reduced to amines (ArNO2 → ArNH2), making nitration an indirect route to aniline derivatives.
Reagents: H2SO4 + SO3 (fuming sulfuric acid, also called oleum).
Electrophile: SO3 or its protonated form SO3H+.
SO3 is generated in situ and has resonance structures showing positive charge on sulfur.
The ring attacks the electrophilic sulfur, forming an arenium ion. A base removes the proton to give the arenesulfonic acid (ArSO3H).
Key difference from other EAS reactions: sulfonation is reversible.
Sulfonation is favoured in concentrated, fuming sulfuric acid.
Desulfonation is favoured in hot, dilute aqueous acid.
The SO3H group can also be replaced by nucleophiles under vigorous conditions (e.g. converting toluene-4-sulfonic acid to 4-methylphenol with NaOH at high temperature).
This reversibility makes sulfonation useful as a temporary blocking group in synthesis.
Reagents: an acyl chloride (RCOCl) + AlCl3.
Electrophile: the acylium ion (RCO+), formed when AlCl3 abstracts the chloride.
RCOCl + AlCl3 → RCO+ + AlCl4 minus
The acylium ion is resonance-stabilised (C triple-bond O with positive charge on C, or C double-bond O with positive charge shared). This stabilisation means it does not rearrange.
The ring attacks the acylium ion, and Cl minus (from AlCl4 minus) deprotonates the arenium ion.
Product: an aryl ketone (ArCOR).
The product is trapped as a complex with AlCl3 (the ketone oxygen coordinates to the Lewis acid), making the product less reactive than the starting benzene. This means acylation stops after monosubstitution, so over-acylation does not occur.
Limitation: acylation cannot occur on rings bearing strongly electron-withdrawing ("deactivated") substituents, because the ring is not nucleophilic enough.
Reagents: an alkyl halide (RCl) + AlCl3 (or FeCl3). Also works with alkenes + acid or tertiary alcohols + BF3.
Electrophile: a carbocation, generated in various ways:
From alkyl halides: RCl + AlCl3 → R+ + AlCl4 minus
From alkenes: protonation of the double bond by a strong acid (e.g. HF, H2SO4) generates a carbocation, which can be captured by the ring.
From alcohols: coordination with BF3 promotes loss of water, leaving a carbocation. For example, (CH3)3COH + BF3 → (CH3)3C+ + ...
The ring attacks the carbocation, and deprotonation restores aromaticity.
Four important limitations of Friedel-Crafts alkylation:
(1) Vinyl and aryl halides do not form stable carbocations, so they do not react.
(2) The reaction requires an electron-rich ring. Rings with electron-withdrawing groups (deactivated rings) do not undergo Friedel-Crafts alkylation.
(3) Over-alkylation is a problem. The alkyl product is more electron-rich than benzene itself, making it more reactive toward further alkylation. This leads to polyalkylated products.
(4) Carbocation rearrangements occur. A primary carbocation can rearrange (via hydride or methyl shift) to a more stable secondary or tertiary carbocation before it reacts with the ring. For example, 1-chloropropane + AlCl3 gives isopropylbenzene, not n-propylbenzene, because the primary cation rearranges to a secondary one.
To place a straight-chain alkyl group on a ring without rearrangement or over-alkylation, use acylation followed by reduction of the carbonyl.
Step 1: Friedel-Crafts acylation with RCOCl / AlCl3 gives ArCOR.
Step 2: reduce the ketone to a CH2 group.
Clemmensen reduction: Zn/Hg, HCl (acidic conditions)
Wolff-Kishner reduction: H2NNH2, then KOH with heat (basic conditions)
Advantage: acylation gives only the monosubstituted product and the acylium ion never rearranges.
Disadvantage: requires two steps instead of one, and acylation cannot be done on deactivated rings.
Reaction | Reagents | Electrophile | Product |
|---|---|---|---|
Bromination | Br2 / FeBr3 | "Br+" (polarised complex) | ArBr |
Chlorination | Cl2 / FeCl3 | "Cl+" (polarised complex) | ArCl |
Iodination | I2 / CuCl2 or H2O2 | "I+" | ArI |
Nitration | HNO3 / H2SO4 | NO2+ | ArNO2 |
Sulfonation | SO3 / H2SO4 (fuming) | SO3 or SO3H+ | ArSO3H |
F-C Acylation | RCOCl / AlCl3 | RCO+ (acylium) | ArCOR |
F-C Alkylation | RCl / AlCl3 | R+ (carbocation) | ArR |
Nitration is the first step in manufacturing TNT (2,4,6-trinitrotoluene) and is also the entry point for synthesising aniline dyes and sulfa drugs, since the nitro group is readily reduced to an amine. Friedel-Crafts acylation is used industrially to make ibuprofen precursors. Sulfonation is employed to make detergents (linear alkylbenzene sulfonates) and as a blocking-group strategy in pharmaceutical synthesis.
Students often confuse the electrophile for each reaction. A reliable exam strategy is to memorise the electrophile for each of the five EAS reactions and how it is generated.
A frequent mistake is writing NO2 minus or NO3 minus as the electrophile in nitration. The electrophile is NO2+ (nitronium ion), not the nitrate or nitrite anion.
Many students forget that Friedel-Crafts alkylation can produce rearranged products. If you see a primary alkyl halide with AlCl3, always check for a possible hydride or methyl shift.
Students sometimes assume all EAS reactions are irreversible. Sulfonation is the important exception: it can be reversed in hot, dilute acid.
⚠️ You will very likely be asked to identify the correct reagents for a given EAS product. Practise working backwards from the product to the required electrophile and reagent set.
⚠️ Questions about Friedel-Crafts alkylation rearrangements are extremely common. Be ready to draw the carbocation rearrangement and predict the actual (rearranged) product.
⚠️ "How would you prepare n-butylbenzene from benzene?" is a classic question that tests whether you know to use the acylation-reduction sequence rather than direct alkylation.
⚠️ Know that sulfonation is reversible and be able to explain the conditions that favour sulfonation vs desulfonation.
Fill in the blank: The electrophile in nitration is _______, generated from HNO3 and H2SO4.
True or false: Friedel-Crafts acylation often leads to polysubstituted products because the product is more reactive than benzene.
Fill in the blank: To reduce a Friedel-Crafts acylation product (an aryl ketone) to an alkylbenzene under acidic conditions, use _______ reduction.
True or false: Sulfonation of benzene is irreversible under all conditions.
Fill in the blank: In Friedel-Crafts alkylation, a primary carbocation can rearrange via a _______ shift to form a more stable secondary or tertiary carbocation.
Q: What reagents would you use to convert benzene to nitrobenzene? Write the mechanism, identifying the electrophile.
A: Use HNO3 and H2SO4. H2SO4 protonates HNO3, which loses water to generate NO2+ (the nitronium ion). The benzene pi electrons attack NO2+, forming an arenium ion with the positive charge delocalised over three ring carbons. Water acts as a base to remove the proton from the sp3 carbon, yielding nitrobenzene and H3O+.
Q: Explain why treating benzene with 1-chloropropane and AlCl3 gives isopropylbenzene rather than n-propylbenzene.
A: AlCl3 promotes ionisation of 1-chloropropane toward a primary carbocation, which is unstable. A 1,2-hydride shift converts the primary carbocation to a more stable secondary carbocation (isopropyl cation). This rearranged cation is the actual electrophile that reacts with benzene, giving isopropylbenzene.
Q: Outline a two-step synthesis of n-hexylbenzene from benzene that avoids rearrangement and over-alkylation.
A: Step 1, Friedel-Crafts acylation with hexanoyl chloride (CH3(CH2)4COCl) and AlCl3 to give phenyl pentyl ketone. Step 2, Clemmensen reduction (Zn/Hg, HCl) or Wolff-Kishner reduction (H2NNH2, KOH, heat) to convert the ketone carbonyl to a CH2, yielding n-hexylbenzene.
Q: Why is sulfonation useful as a "blocking group" strategy in aromatic synthesis?
A: Because sulfonation is reversible. You can sulfonate a position to block it from further electrophilic attack, carry out other EAS reactions on the remaining positions, and then remove the SO3H group by treating with hot, dilute aqueous acid (desulfonation). This gives you control over the substitution pattern that would be difficult to achieve otherwise.
Q: Why does Friedel-Crafts acylation stop at monosubstitution, while alkylation tends to give polysubstituted products?
A: In acylation, the product ketone forms a complex with AlCl3 through its carbonyl oxygen. This complex deactivates the ring (makes it less electron-rich), preventing a second acylation. In alkylation, the alkyl product is more electron-rich than benzene, so it reacts faster with the next equivalent of electrophile, leading to di- and trialkylated products.
These reactions connect to carbonyl chemistry (the acylium ion in Friedel-Crafts acylation, the Clemmensen and Wolff-Kishner reductions). Carbocation rearrangements in Friedel-Crafts alkylation draw on the same principles covered in alkene addition and SN1 reactions (Ch 5–7). Substituent effects and directing groups (covered in Part 3 of these notes) determine where on the ring new electrophiles are placed, and that topic depends on understanding the arenium ion intermediates introduced here.
halogenation, bromination, chlorination, iodination, nitration, nitronium ion, NO2+, sulfonation, desulfonation, fuming sulfuric acid, Friedel-Crafts, acylation, alkylation, acylium ion, carbocation rearrangement, hydride shift, over-alkylation, polyalkylation, Clemmensen reduction, Wolff-Kishner reduction, acyl chloride, AlCl3, FeBr3, Lewis acid catalyst, aryl ketone, blocking group strategy, organic chemistry chapter 12