Organic Chemistry · Part 5 of 9

Rearrangements

Named Reactions, Part 5 · 21 sections · about 18,909 words · CSIR-NET Chemical Sciences, GATE Chemistry & IIT-JAM

What happens when a molecule reorganises its own skeleton — a group migrates with its bonding electrons from one atom to an adjacent (or, in sigmatropic shifts, a remote) atom, giving a constitutionally different product. Two layers on every reaction: a hand-held beginner path (plain “what it does”, arrow-by-arrow mechanism, graded worked examples, trap boxes) and a research-grade advanced/reference path (stereoelectronics, migratory-aptitude series, antiperiplanar migration geometry, chair-like [3,3] transition states, suprafacial/antarafacial analysis, isotope-labelling & stereochemical evidence for concerted vs stepwise pathways, scope & FG tables, and modern asymmetric variants). Carbocation 1,2-shifts: Pinacol–pinacolone, Wagner–Meerwein, semipinacol. Migration to nitrogen: Beckmann, Hofmann, Curtius, Lossen, Schmidt. Carbene / carbanion: Wolff & Arndt–Eistert, Favorskii, benzilic acid. [3,3]-sigmatropic: Claisen & Cope (oxy-Cope, aza-Cope, Ireland– and Johnson–Claisen). Aromatic / ylide: Fries, Stevens & Sommelet–Hauser ([1,2] vs [2,3]), dienone–phenol — closing with a “which rearrangement is this?” decision map.

The 21 sections in Part 5

  • 1The 1,2-shift and migratory aptitude (do this first) Free below
  • 2The Pinacol–pinacolone rearrangement
  • 3The Wagner–Meerwein rearrangement
  • 4The Semipinacol rearrangement
  • 5The common thread: acyl nitrene / N–LG, and the isocyanate
  • 6The Beckmann rearrangement
  • 7The Hofmann rearrangement (bromamide degradation)
  • 8The Curtius rearrangement
  • 9The Lossen rearrangement
  • 10The Schmidt reaction
  • 11The Wolff rearrangement & Arndt–Eistert homologation
  • 12The Favorskii rearrangement
  • 13The Benzilic acid rearrangement
  • 14Nomenclature, Woodward–Hoffmann rules, and the chair TS
  • 15The Claisen rearrangement ([3,3], with O)
  • 16The Cope rearrangement ([3,3], all-carbon) & the oxy-Cope
  • 17The Fries rearrangement
  • 18The Stevens [1,2] & Sommelet–Hauser [2,3] rearrangements
  • 19The Dienone–phenol rearrangement
  • 20A four-question triage
  • 21Master comparison tables

The 1,2-shift and migratory aptitude (do this first)

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Section G.0 of Part 5, reproduced in full from the book — figures and all. No sign-in, no paywall on this section.

Beginner layer

One picture explains Pinacol, Wagner–Meerwein, Beckmann, Hofmann, Curtius and more: a group hops one atom over, into an electron-poor site, carrying its electrons.

In one line: in a 1,2-shift, a group R (a hydrogen, an alkyl group, or an aryl group) moves from one atom to the next-door atom that is short of electrons, taking the two bonding electrons with it. The electron-deficient site is filled, and the deficiency (the +) reappears where R started. Rearrangements happen when the new arrangement is more stable — a better carbocation, an aromatic ring, or a neutral molecule.

The 1,2-shift (the engine of almost every cationic rearrangement)CCelectron-deficientRmigrating group(with its bond pair)R migrates Cα→Cβ; the + relocates onto Cα(net: a constitutionally different, usually more stable, cation)
A group R (H, alkyl, or aryl) leaves Cα and bonds to the adjacent electron-deficienttaking its bonding electron pair with it. The positive charge (or empty orbital) therefore moves from Cβ onto Cα. The migration is concerted and, at the migration origin and terminus, proceeds with retention of configuration in the migrating group and suprafacial delivery. Hand-built —
Migratory aptitude = the relative tendency of different groups to be the one that migrates when there is a choice. The broadly quoted order is aryl > H ≈ 3° alkyl > 2° alkyl > 1° alkyl > CH₃, and among aryl groups, rings with electron-donating para substituents migrate fastest (they stabilise the bridged, partially-positive transition state). The order is not absolute — it shifts with the exact reaction, geometry and conditions.
Rough migratory-aptitude ranking. Aryl groups win because they can form a bridged phenonium-type transition state that delocalises the developing positive charge. Structures are RDKit depictions of the parent hydrocarbons of the groups, not the TS. H (hydride) is deliberately not depicted — a migrating H is an atom, not a molecule — but it belongs high in this order, roughly alongside 3° alkyl and often beating aryl.
Mechanism — Why a 1,2-shift happens (three ideas)
  1. An empty orbital must be adjacent. The migration terminus is electron-deficient — a carbocation (pinacol, Wagner–Meerwein), an electron-poor N (Beckmann, Hofmann, Curtius, Schmidt), or a carbene (Wolff). No adjacent empty/low-lying orbital → no shift.
  2. Geometry: antiperiplanar. The migrating σ-bond must be parallel to (aligned with) the empty orbital — roughly anti-periplanar to the leaving group. This alignment lets the bonding electrons overlap the empty orbital in the transition state.
  3. Driving force: a more stable product. The shift is chosen that gives the more stable cation (3°>2°>1°, or benzylic/allylic), or that leads on to a neutral product (loss of a proton, trapping by water). If the start is already the most stable, no rearrangement occurs.

Which shift: a 2° carbocation with a 3° centre next door Easy

Draw the cation and look at the neighbours of the C⁺.
A hydride or methyl shift from the adjacent 3° carbon would convert a cation into a cation — more stable.
So a 1,2-hydride shift (fast, low barrier) occurs to give the tertiary cation. This is the classic “rearrangement to a more stable carbocation”.

Retention or inversion in the migrating group? Medium

The migrating group keeps its electron pair and moves through a three-centre, two-electron bridged transition state.
Because the group never fully leaves and re-adds, its own stereocentre is retained (migration proceeds with retention of configuration at the migrating carbon).
At the migration terminus, delivery is suprafacial (same face). These are classic labelling results you should be able to state.

⚠ Common mistakes & exam traps

  • A rearrangement only happens if it improves stability. Do not ‘rearrange’ a tertiary cation down to a secondary one.
  • Migratory aptitude is context-dependent. The aryl>H>alkyl order is a guide, not a law — in some reactions H migrates faster than aryl; in Beckmann only the group anti to the leaving group migrates regardless of aptitude.
  • The group migrates with its bonding pair (nucleophilic migration to an electron-poor centre). Do not draw the electrons going the wrong way.
  • Ring-expansion / ring-contraction is just a 1,2-shift where the migrating bond is part of a ring — watch for strained rings that relieve strain by rearranging.
Advanced / reference layer

Bridged (non-classical) transition states, stereochemistry of migration, quantitative aptitude, and how Part 5 is organised by the nature of the electron-deficient terminus.

Mechanistically the 1,2-shift is a [1,2]-sigmatropic shift of a σ-bond to an empty (or low-lying) orbital. The transition state is a three-centre, two-electron bridge: the migrating group is partially bonded to both origin and terminus, so the migration is concerted, intramolecular, suprafacial, and proceeds with retention of configuration in the migrating group. Where the bridge is deep enough to be an intermediate (e.g. the phenonium ion, or the 2-norbornyl cation) the species is called non-classical; where it is only a saddle point it is a classical TS. The distinction was the subject of the decades-long non-classical carbocation debate (Winstein vs H. C. Brown).

Stereochemical and labelling signatures (what proves the mechanism)

ObservationWhat it demonstrates
Retention of configuration in the migrating CConcerted, bridged migration (group never becomes free)
Antiperiplanar migrating bond / leaving groupσ(C–R) must overlap the developing empty orbital
Intramolecularity (crossover experiments show no scrambling)Migration is within one molecule, not via free fragments
Only the anti group migrates (Beckmann of oximes; Schmidt of ketones)Migration is concerted with loss of the leaving group
Retention of the migrating group’s chirality in Curtius/HofmannR→N migration is concerted, suprafacial
These five results recur across the whole family and are examiners’ favourite ‘evidence’ questions.

Migratory aptitude — the finer print

The observed order aryl > H > alkyl reflects the ability of the migrating group to stabilise positive charge in the bridged TS. p-Anisyl (4-MeO-C₆H₄) > p-tolyl > phenyl > p-chlorophenyl > p-nitrophenyl tracks the Hammett σ of the para substituent (EDG accelerate). However, aptitude can invert with mechanism: when migration and ionisation are concerted, the group that is antiperiplanar migrates whatever its intrinsic aptitude; when a discrete cation forms first (stepwise), intrinsic aptitude dominates. Conformational access therefore often beats electronic aptitude.

How Part 5 is organised (by the electron-deficient terminus)

Terminus (where R migrates TO)FamilyNamed reactions
Carbocation C⁺G. Carbocation shiftsPinacol–pinacolone, Wagner–Meerwein, semipinacol
Electron-poor nitrogen (nitrene / N–LG)H. Migration to nitrogenBeckmann, Hofmann, Curtius, Lossen, Schmidt
Carbene / carbanion carbonI. Carbene & carbanionWolff (+Arndt–Eistert), Favorskii, benzilic acid
Concerted 6-electron pericyclic (no charge)J. [3,3]-sigmatropicClaisen, Cope (+ oxy-/aza-/Ireland/Johnson)
Aromatic ring / ammonium ylideK. Aromatic & ylideFries, Stevens, Sommelet–Hauser, dienone–phenol
The whole Part hangs on ‘where is the electron-deficient site, and which group is best placed to migrate into it?’
Easy
Predict whether neopentyl cation, (CH₃)₃C–CH₂⁺, will rearrange, and to what.
Show solution
Yes. The primary neopentyl cation undergoes a 1,2-methyl shift: a methyl migrates from the quaternary carbon to the CH₂⁺, converting a cation into the far more stable tert-amyl cation (CH₃)₂C⁺–CH₂CH₃. This is the textbook driving-force example.
Med
In an acid-catalysed rearrangement a substrate bearing both a p-methoxyphenyl and a p-nitrophenyl group at the migration origin gives >95% migration of the anisyl group. Explain.
Show solution
Migration proceeds through a bridged (phenonium-like) TS in which the migrating aryl ring bears partial positive charge. A p-methoxy (EDG) ring stabilises that charge strongly; a p-nitro (EWG) ring destabilises it. So the anisyl group has the higher migratory aptitude and migrates selectively — a Hammett-type electronic effect (ρ < 0).
Hard
Distinguish, with an experiment, a concerted 1,2-shift from a stepwise mechanism that goes through a free carbocation.
Show solution
Use a stereochemically labelled migrating carbon and/or a crossover experiment. A concerted shift gives retention at the migrating carbon and no crossover (fully intramolecular). A free cation would allow racemisation/scrambling and, in crossover experiments, mixed products. Rate insensitivity to added external nucleophile and a negative ρ also support the concerted bridged pathway.

Framing chapter; primary citations live in each reaction below.

  • The 1,2-shift, bridged transition states and migratory aptitude are standard treatments in Clayden, Organic Chemistry, and Carey & Sundberg, Advanced Organic Chemistry, Part A.

Read the rest of Part 5

The remaining 20 sections of this part — The Pinacol–pinacolone rearrangement, The Wagner–Meerwein rearrangement, The Semipinacol rearrangement, The common thread: acyl nitrene / N–LG, and the isocyanate — and all nine parts of Named Reactions are part of ChemVidya Full Access, along with the other books, 55 Study Notes and 6,000+ practice questions.

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