Organic Chemistry · Part 8 of 9

Aromatic Substitution Mechanisms

Reaction Mechanisms, Part 8 · 9 sections · about 19,558 words · CSIR-NET Chemical Sciences, GATE Chemistry & IIT-JAM

Aromatic rings react by mechanisms that exist nowhere else, because the ring insists on getting its aromaticity back. This part covers all four routes — the familiar electrophilic one, the addition–elimination that needs electron-withdrawing groups, the elimination–addition that goes through a triple bond inside a ring, and the radical chain that needs none of the above. It then does what most textbooks skip: shows how directing effects are measured rather than merely asserted. Two layers on every section: a slow, hand-held beginner path and a research-grade advanced/reference path.

The 9 sections in Part 8

  • 1The two-step mechanism, the arenium ion, and the evidence that step 1 is rate-determining Free below
  • 2Making the electrophile: nitration, halogenation, sulfonation and Friedel–Crafts
  • 3Activating and deactivating groups — and why the halogens break the pattern
  • 4Ortho:para ratios, competing substituents and the order of a synthesis
  • 5Nucleophilic aromatic substitution by addition–elimination: the Meisenheimer complex
  • 6Benzyne and the SRN1 radical chain — substitution without activation
  • 7Partial rate factors — measuring a directing effect instead of asserting it
  • 8The Hammett equation, σ+ and σ−
  • 9What a change in ρ tells you — and where this goes next

The two-step mechanism, the arenium ion, and the evidence that step 1 is rate-determining

Free extract

Section H.1 of Part 8, reproduced in full from the book — figures and all. No sign-in, no paywall on this section.

Beginner layer

Two steps, one intermediate, and one experiment that settles which step is slow. Get this section right and three-quarters of the topic follows.

Electrophilic aromatic substitution is two steps, never one. Not ‘usually two’ — two, with an intermediate that has been isolated, crystallised and structurally characterised.

Mechanism — electrophilic aromatic substitution (SEAr), general
  1. Step 1 — addition of the electrophile (slow, rate-determining). Two π electrons of the ring reach out to E+. One ring carbon becomes sp3, carrying both the incoming electrophile and its original hydrogen. The aromatic sextet is destroyed and a delocalised cation — the arenium ion — is formed. This step is strongly endothermic, because it is here that the 150 kJ mol−1 of aromatic stabilisation is surrendered.
  2. Step 2 — loss of the proton (fast). A base — the conjugate base of the acid used to make the electrophile, or the solvent, or the counterion AlCl4/HSO4 — removes the hydrogen from the sp3 carbon. The C–H bonding pair drops into the ring, the sextet reforms, and the whole 150 kJ mol−1 comes back. Strongly exothermic and effectively irreversible.
  3. Net result: Ar–H + E+ → Ar–E + H+. The electrophile has taken the hydrogen’s place; the ring is aromatic again.
Arenium ion (Wheland intermediate, σ complex, benzenonium ion): the cationic intermediate of electrophilic aromatic substitution. One ring carbon is sp3 and bears two σ substituents (the electrophile and the hydrogen); the remaining five carbons carry four π electrons in a delocalised pentadienyl cation. It is a real intermediate sitting in a potential-energy well, not a transition state.

Four names, one species. Wheland intermediate honours G. W. Wheland, who first used it to rationalise directing effects. σ complex distinguishes it from the weakly bound π complex that precedes it. Benzenonium or benzenium ion is the systematic name of the parent C6H7+. Examiners use all four interchangeably.

Where the positive charge actually sits — and where it does not

This is the single most misdrawn structure in the whole of organic chemistry, so slow down here. The sp3 carbon — the one bearing the new electrophile — has four σ bonds and no p orbital. It cannot carry positive charge. It is not part of the delocalised system at all; it is an insulator sitting in the ring, and its whole function is to break the conjugation into a five-carbon chain.

The charge is spread over the other five carbons, and even then not evenly. A pentadienyl cation puts its charge on alternate atoms — positions 1, 3 and 5 of the five-carbon chain. Numbering the ring from the sp3 carbon, those are the two ortho carbons and the para carbon. The two meta carbons carry essentially none.

The arenium ion — all three resonance formsHE+HE+HE+HEδ+δ+δ+orthoparaortho′delocalised compositeThe sp³ carbon (top of every ring) carries H and E and is NEVER positive. Charge alternates over the other five carbons.
The three contributing structures of a benzene-derived arenium ion, and the delocalised picture they add up to. The apex carbon in every drawing is sp3: it holds the hydrogen (black) and the electrophile (teal) and has no p orbital. The four remaining π electrons run over the other five carbons as a pentadienyl cation, so the positive charge appears at the two ortho positions and the para position and nowhere else. Every directing effect in H.3 is read off this picture: a substituent helps if it sits on a carbon that is positive in one of these forms.

The same molecule, drawn by RDKit from an explicit Lewis structure, makes the point again — note which carbon carries the plus:

The energy profile: two humps, and the first one is taller

Free-energy profile for electrophilic aromatic substitutionG →reaction coordinate →ArH + E⁺TS-1 ‡TS-2 ‡arenium ionArE + H⁺ΔG₁‡ΔG₂‡ (small)ΔG₁‡ >> ΔG₂‡: step 1 is rate-determining, and the C–H bond is nottouched until after the barrier has been crossed.
Why the first step is the slow one. Getting to TS-1 means paying for the loss of aromaticity while gaining only a partial C–E bond, so the first barrier is large. The arenium ion sits in a shallow well. Getting out of it to TS-2 needs almost nothing, because from the intermediate onwards the reaction is running downhill into a restored aromatic sextet. Two consequences follow immediately: (i) the product distribution is decided at TS-1, so everything about orientation is a statement about arenium-ion stability (Hammond’s postulate — TS-1 resembles the intermediate); (ii) since the C–H bond is intact at TS-1, replacing that hydrogen with deuterium should change nothing. That prediction is testable, and it is tested below.

The isotope-effect test, in one page

Suppose you did not know which step was slow. There is a clean experiment. Deuterium is twice as heavy as protium, so a C–D bond vibrates more slowly than a C–H bond — about 2200 cm−1 against 3000 cm−1 — and therefore sits lower in its potential well by half that difference in vibrational wavenumber, which is the difference in zero-point energy. If the bond is being broken in the rate-determining step, the deuterated compound starts from further down and has a taller hill to climb, so it reacts more slowly.

kH/kD ≈ exp[(ZPEH − ZPED)/RT]   with   ZPEH − ZPED = ½hc(ν̃CH − ν̃CD) ≈ 400 cm−1 ≈ 4.8 kJ mol−1  ⇒  kH/kD ≈ 7 at 25 °C
Primary kinetic isotope effect: the rate change seen when an atom whose bond is broken in the rate-determining step is replaced by a heavier isotope. For C–H/C–D the theoretical ceiling at room temperature is about 7; values of 2–7 are diagnostic of C–H cleavage in the slow step. A value of 1.0–1.2 says the C–H bond is not being broken there.

The experiment was done by Lars Melander in the early 1950s. He nitrated and brominated benzene, toluene and naphthalene that had been labelled with deuterium and with tritium, and measured how much slower the labelled positions reacted. The answer was: they did not react more slowly at all. Within experimental error, kH/kD = 1.

Nitration: C6H6 vs C6D6  →  kH/kD ≈ 1.0  —  no primary isotope effect.
Bromination, chlorination, Friedel–Crafts: same answer.
Conclusion: the C–H bond is intact at the rate-determining transition state ⇒ proton loss is not the slow step ⇒ step 1 is rate-determining.
Note: Read the logic in the right direction. The absence of an isotope effect does not prove that the mechanism has two steps — it proves that whatever the mechanism is, C–H cleavage happens after the rate-determining transition state. Combined with the independent evidence that the arenium ion exists (below), that pins down the two-step scheme. An exam answer that says ‘no KIE, therefore two steps’ has skipped a link.

A student proposes that electrophilic aromatic substitution is a single concerted step in which E+ comes in as H+ leaves, like an SN2 at carbon. Design the experiment that kills this proposal, and state what result you expect. Easy

What the proposal requires. If addition of E+ and loss of H+ are concerted, the C–H bond must be partly broken at the single transition state — there is no other transition state for it to break at.
The probe. Prepare the same arene with H and with D at the position being substituted (C6H6 and C6D6 are the simplest pair) and measure both rates under identical conditions.
Prediction if concerted. A substantial primary isotope effect, kH/kD in the range 2–7.
Observation. For nitration and for bromination, kH/kD = 1.0 ± experimental error. The concerted proposal is dead.
The refinement worth adding. A very small inverse secondary effect (kH/kD slightly below 1) is actually expected, because the ipso carbon changes from sp2 to sp3 in step 1 and the C–H bending vibrations stiffen. Seeing a value marginally under unity is a confirmation of the two-step picture, not a contradiction of it.

⚠ Common mistakes & exam traps

  • Never put the positive charge on the carbon bearing the electrophile. That carbon is sp3, has four σ bonds and no p orbital, and is the one carbon in the arenium ion that cannot be positive. Charge lives on the two ortho carbons and the para carbon relative to it.
  • Do not expect a primary isotope effect in ordinary SEAr. For nitration, bromination, chlorination and Friedel–Crafts, kH/kD = 1.0. If a question reports a KIE of 1 and asks what it tells you, the answer is ‘C–H cleavage is after the rate-determining step’, not ‘the reaction is not SEAr’.
  • The arenium ion is an intermediate, not a transition state. It sits in a well, it can in favourable cases be isolated, and it must be drawn with full bonds and a full charge — never with dashed partial bonds and a double dagger.
  • Do not draw four π electrons over six carbons. The delocalisation in the arenium ion runs over five carbons only. Drawing a circle inside the whole ring with a plus in the middle says the intermediate is aromatic, which is exactly the opposite of what makes step 1 slow.
  • ‘Slow step’ is not ‘the step with the higher-energy product’. It is the step with the higher transition state. In SEAr the two happen to coincide, but the reasoning must be about TS-1.
Advanced / reference layer

Direct observation of the intermediate; the π complex that precedes it; the steady-state condition that decides whether an isotope effect appears; and the reactions where one does.

The arenium ion has been seen

Wheland proposed the intermediate in 1942 as a bookkeeping device. It is now a compound. The essential experimental move is to remove every base from the medium, so that step 2 has nothing to react with. In superacid media — HF/SbF5, FSO3H/SbF5 — the conjugate base is so feeble that the cation simply sits there.

  • Benzene + HF/BF3 at low temperature gives a stable solution of the benzenium ion C6H7+. Its 1H NMR spectrum shows the two protons on the sp3 carbon far upfield of the ring protons, exactly as an sp3 CH2 in a non-aromatic ring should be, and the 13C spectrum shows the characteristic huge downfield shifts at the ortho and para carbons that carry the charge.
  • Heptamethylbenzenium salts — from hexamethylbenzene plus a methylating agent — are crystalline. Their X-ray structures show the tetrahedral sp3 carbon and the alternating short/long bonds of a pentadienyl cation around the rest of the ring.

π complex, encounter complex, σ complex

Between free reactants and the arenium ion there is at least one shallower minimum, and distinguishing them matters for the very fast reactions in H.7.

SpeciesBondingGeometryLifetime / role
Encounter pairnone — simply two molecules in the same solvent cageunchangedSets the ceiling on rate. When every encounter leads to reaction the process is encounter-controlled and no substituent can make it faster
π complexelectrophile accepts electron density from the whole π cloudelectrophile sits above the ring plane; all six carbons still sp2 and equivalentWeak (a few kJ mol−1), no positional selectivity, aromaticity preserved. Benzene·HCl and benzene·Br2 complexes are of this kind
σ complex = arenium iona full C–E σ bondelectrophile in the ring plane at one carbon, which is now sp3The real intermediate. All the positional selectivity is created on the way to this
The practical test: π-complex formation shows almost no substituent dependence (K for benzene vs toluene differ by a factor near 1), whereas σ-complex formation shows factors of hundreds. Positional selectivity therefore cannot be decided at the π complex.

When does an isotope effect appear? The steady-state criterion

Write the mechanism with the second step made explicit as a base-mediated deprotonation, and apply the steady-state approximation to the arenium ion:

ArH + E+  k1k−1  [ArHE]+  k2[B] →  ArE + BH+
rate = k1k2[ArH][E+][B] / (k−1 + k2[B])

Two limits, and they are the whole story:

RegimeRate law collapses toIsotope effect?Base catalysis?
k2[B] >> k−1
(the arenium ion loses H+ faster than it can spit the electrophile back out)
rate = k1[ArH][E+]None — kH/kD = 1None — rate independent of [B]
k−1 >> k2[B]
(step 1 is a fast pre-equilibrium; deprotonation is the bottleneck)
rate = (k1/k−1)k2[ArH][E+][B]Yes — a full primary effect, 2–7Yes — rate first order in base
This table is the examinable content of the whole isotope-effect discussion. Note that the two diagnostics travel together: whenever a primary KIE turns up in an aromatic substitution, general base catalysis turns up with it. Finding one without the other should make you suspicious of the data.

So the question ‘why is there no isotope effect?’ becomes the sharper question ‘why is k−1 so small?’ — and the answer is that for a good electrophile the C–E bond just formed is strong and the reverse step would have to expel a high-energy cation. Reversal of nitration would mean expelling NO2+ from a neutral compound; it does not happen. The exceptions are precisely the cases where the C–E bond is weak, or the electrophile is stable enough to leave again, and something slows the deprotonation down.

The three genuine exceptions

1. Sulfonation. Sulfonation of benzene shows a small but real primary isotope effect, of order kH/kD ≈ 1.5–2. Two things conspire. The arenium ion formed from SO3 is a zwitterion, ArH(SO3)+, in which the negative sulfonate end is a perfectly good leaving group — so k−1 is large. And SO3 leaves as a stable neutral molecule rather than as a high-energy cation, which is exactly what nitration cannot do. The result is k−1 a non-negligible fraction of k2[B] — about a seventh of it, as the worked example below shows — which is exactly the intermediate regime: a partial isotope effect, well below the maximum of 7. The very same large k−1 is why sulfonation is the one classical electrophilic aromatic substitution that is reversible overall — the strategic consequence of which is H.4 in the next module.

2. Diazo coupling. An arenediazonium ion ArN2+ is a feeble electrophile — it will only attack rings as electron-rich as phenoxide or a naphthylamine. Feeble electrophile means weak new C–N bond means large k−1. Zollinger’s classic study coupled diazotised sulfanilic acid with 2-naphthol-6,8-disulfonate, where coupling occurs at C-1, flanked by the bulky 8-sulfonate group. The steric crowding slows the removal of the C-1 hydrogen, cutting k2. Both effects push the system into the pre-equilibrium regime, and the observed isotope effect climbs to kH/kD ≈ 6.5 — close to the theoretical maximum — accompanied, as the table predicts, by clean general base catalysis by pyridine. Unhindered couplings (for example with 1-naphthol) show no isotope effect at all: the exception is structural, not a property of diazo coupling as a class.

3. Sterically obstructed halogenation and some iodinations. Brominate 1,3,5-tri-tert-butylbenzene and an isotope effect appears, because the flanking tert-butyl groups make the hydrogen on the sp3 carbon very hard for a base to reach. Iodination is the other recurring case: I+-type electrophiles are weak and the C–I bond is weak, so k−1 is large and iodinations of activated substrates such as phenol and aniline commonly show kH/kD in the range 3–4 together with base catalysis.

ReactionElectrophilekH/kDInterpretation
NitrationNO2+≈ 1.0k2[B] >> k−1; step 1 fully rate-determining
Bromination (ordinary substrates)Br2·FeBr3≈ 1.0as above
Friedel–Crafts alkylation / acylationR+ / RCO+≈ 1.0as above
SulfonationSO3≈ 1.5–2intermediate regime; k−1 a non-negligible fraction of k2[B] — and hence overall reversibility
Iodination (activated arenes)I+ equivalent≈ 3–4weak electrophile, weak C–I bond, large k−1
Diazo coupling, hinderedArN2+up to ≈ 6.5pre-equilibrium regime; base catalysis observed
Bromination of 1,3,5-tri-t-Bu-benzeneBr2large (> 3)deprotonation sterically obstructed, k2 small
Learn the pattern, not the digits: an isotope effect appears when the electrophile is weak (so the arenium ion falls back apart easily) or when the proton is hard to reach (so it cannot leave quickly).

The sulfonation of benzene shows kH/kD = 1.7, whereas its nitration shows 1.0. A student concludes that sulfonation must go by a different mechanism. Assess this, and derive the correct conclusion quantitatively. Hard

The student’s error. Both reactions go through an arenium ion by the same two-step scheme. What differs is not the mechanism but which step is rate-determining — and in sulfonation, neither step is, cleanly.
Set up. From the steady-state law, the observed rate constant is kobs = k1k2[B]/(k−1 + k2[B]). Only k2 is isotope-sensitive; write k2H and k2D with the intrinsic ratio k2H/k2D = 7 (the maximum).
Solve. Let r = k−1/(k2H[B]). Divide the H rate constant by the D one, then divide top and bottom of each by k2H[B], remembering that k2D[B] = k2H[B]/7. Then kobsH/kobsD = 7(r + 1/7)/(r + 1) = (1 + 7r)/(1 + r). Setting this equal to 1.7 gives 1 + 7r = 1.7 + 1.7r, so 5.3r = 0.7 and r ≈ 0.13.
Read the answer. r ≈ 0.13 means k−1 is only about 13% of k2[B]: the arenium ion does expel SO3 backwards, but only about once for every eight times it loses its proton forwards. Reversion is a real but minority channel — enough to lift the isotope effect clearly off 1, nowhere near enough to approach 7. That is the ‘in-between’ regime, and it explains the two facts about sulfonation simultaneously — the partial isotope effect, and the reversibility, which needs only that k−1 be non-negligible, not that it dominate.
Sanity check the limits. r → 0 means k2[B] >> k−1 and gives kH/kD → 1 (formation of the arenium ion fully rate-determining, and the C–H bond is untouched in that step); r → ∞ means k−1 >> k2[B] and gives 7 (fast pre-equilibrium, deprotonation fully rate-determining). Both limits reproduce the two-regime table above, so the algebra is sound. Note the calculation depends on the assumed intrinsic maximum of 7; that assumption should be stated in any answer.
Med
Nitration by nitric acid in an organic solvent — nitromethane, acetic acid or sulpholane — is found to be zero order in the arene for very reactive arenes such as mesitylene, but first order in the arene for benzene itself. Explain, and say what this implies about the rate-determining step.
Show solution
In these media nitric acid is only partly ionised, so nitration has a prior step of its own: generation of the electrophile from nitric acid itself. The acid self-ionises, 2HNO3 ⇌ H2NO3+ + NO3, and the protonated nitric acid then loses water in the slow step, H2NO3+ → NO2+ + H2O. For a very reactive arene, every NO2+ that forms is captured immediately, so the rate is simply the rate of making the nitronium ion — independent of which arene is present and of how much of it there is: zero order in arene. For benzene, capture is no longer instantaneous, so the arene concentration enters again. This is a change in the overall rate-determining step from attack on the ring to generation of the electrophile; it does not change the SEAr mechanism itself. The medium matters, and this is the half of the question that is most often got wrong: in mixed nitric/sulfuric acid the nitric acid is essentially completely ionised to NO2+ before any arene is added (that is what the cryoscopy and the Raman line show), so the nitronium ion is preformed and stoichiometric, its formation is fast and never rate-determining, and nitration in mixed acid stays first order in the arene for reactive and unreactive arenes alike. The zero-order regime simply does not arise there. The important corollary is that where the zero-order regime does hold, all reactive arenes react at the same rate, so relative reactivities measured there are meaningless — a point that returns with force in H.7 when partial rate factors are measured.
Hard
Coupling of a diazonium salt with 1-naphthol shows kH/kD = 1.0, but coupling with 2-naphthol-6,8-disulfonate shows kH/kD = 6.5. Both are diazo couplings. Account for the difference.
Show solution
Both go through the same arenium-ion mechanism, and both have a large k−1 because ArN2+ is a weak electrophile. What differs is k2, the deprotonation. In the 6,8-disulfonate case coupling happens at C-1, which is flanked by the bulky 8-sulfonate; a base approaching the C-1 hydrogen is sterically obstructed, so k2 is small and k−1 >> k2[B]. The first step becomes a pre-equilibrium and deprotonation becomes rate-determining, giving a near-maximal primary isotope effect. With 1-naphthol there is no such obstruction, k2[B] >> k−1, and the effect vanishes. The prediction that follows: the disulfonate coupling should also show general base catalysis and the 1-naphthol coupling should not — which is what Zollinger observed.
Easy
Why can the arenium ion be observed by NMR in HF/SbF5 but not in the nitrating mixture where it is formed?
Show solution
Because step 2 needs a base, and the two media differ completely in how much base they contain. In nitrating acid there is plenty of HSO4 and water; the arenium ion is deprotonated as fast as it forms, so its steady-state concentration is far too low to detect. HF/SbF5 is a superacid: its conjugate base SbF6 is one of the least basic anions known, so k2[B] is driven to essentially zero and the cation accumulates. The generalisable lesson: to see a cationic intermediate, remove every base from the medium. That is the whole strategy of superacid chemistry.

Sources for the arenium-ion mechanism and the isotope-effect evidence:

  • Clayden, Greeves & Warren, Organic Chemistry (Oxford University Press) — the chapter on electrophilic aromatic substitution gives the arenium-ion picture and the aromatic-stabilisation argument.

Read the rest of Part 8

The remaining 8 sections of this part — Making the electrophile: nitration, halogenation, sulfonation and Friedel–Crafts, Activating and deactivating groups — and why the halogens break the pattern, Ortho:para ratios, competing… — and all nine parts of Reaction Mechanisms are part of ChemVidya Full Access, along with the other books, 55 Study Notes and 6,000+ practice questions.

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