Rearrangement Reactions
Table of Contents
A rearrangement reaction is an organic reaction in which the connectivity of atoms within a molecule changes because an atom, group, or bond migrates from one position to another. The reaction produces a new molecular structure, although the product is not necessarily a structural isomer of the starting compound. [1–4]
In most rearrangements, the migrating group does not completely detach from the reacting molecule. Bond breaking and bond formation occur together or through a closely connected sequence of steps. For example, in hydride and alkyl shifts, a free hydride ion or alkyl anion is not produced. The group migrates directly with the electrons of its original bond.
Why Rearrangement Reactions Occur
Rearrangements occur when changing the molecular structure provides a more favorable reaction pathway. Common driving forces include: [1,3,4]
- formation of a more stable carbocation or other intermediate
- relief of ring strain
- formation of a stable functional group, such as a carbonyl group
- formation of a particularly stable product
- loss of a stable small molecule
General Mechanism of Stepwise Rearrangements
Rearrangement reactions do not follow one universal mechanism. Many stepwise rearrangements proceed through a reactive intermediate, followed by migration and product formation. Concerted rearrangements, such as the Claisen and Cope rearrangements, occur in a single step and follow a different pathway. [1,3,4]
1. Formation of a reactive intermediate
The starting compound is activated by heat, light, an acid, a base, or another reagent. This may produce a reactive intermediate, such as a carbocation, carbanion, or free radical.
2. Migration and rearrangement
An atom or group becomes bonded at a different position through the reorganization of one or more bonds. In many carbocation rearrangements, a hydrogen atom or alkyl group migrates to an adjacent positively charged carbon together with its bonding electron pair.
A 1,2-hydride shift can be represented as:
R1R2C+–CH(R3)R4 → R1R2CH–C+(R3)R4
The hydrogen on the carbon adjacent to the carbocation migrates with the two electrons of its C–H bond. It forms a new C–H bond at the original carbocation center, while the positive charge appears on the carbon from which the hydrogen migrated.
3. Reaction of the rearranged intermediate
If the rearrangement leaves a reactive intermediate, it undergoes another step—such as nucleophilic attack, elimination, proton transfer, or oxidation—to form the final product.
The overall process may be summarized as:
Starting compound → Reactive intermediate → Rearranged intermediate → Product
Ring Expansion and Contraction
Ring expansion and ring contraction are skeletal rearrangements in which the number of atoms forming a ring changes. These reactions may be driven by relief of ring strain, formation of a more stable intermediate or product, formation of a stable functional group, or removal of a small molecule. [1,3,4]
Ring expansion occurs when the number of atoms in a ring increases. It commonly involves the migration of a carbon–carbon bond to a neighboring reactive center, causing an adjacent atom to become part of the ring.
Expansions of three- and four-membered rings are particularly common because they can reduce ring strain. A cyclobutylmethyl carbocation may rearrange to a cyclopentyl carbocation. The migration enlarges the four-membered ring to a five-membered ring and reduces ring strain.
Ring contraction occurs when the number of atoms in a ring decreases. It may involve migration of a ring bond, cleavage and reformation of bonds, or extrusion of an atom or small molecule. The atom removed from the ring may remain in the product as part of a substituent or may leave the molecule.
In the Favorskii rearrangement of a cyclic α-halo ketone, the ring may contract by one carbon atom while forming a carboxylic acid derivative.
Types of Rearrangements
| Type | Basic feature | Examples |
|---|---|---|
| Carbocation rearrangement [1,3,4] | A hydride, alkyl group, or ring bond migrates to an adjacent positively charged carbon | 1,2-hydride shift, 1,2-alkyl shift, ring expansion |
| Anionic rearrangement | Skeletal reorganization proceeds through an anionic or electron-rich intermediate | Favorskii rearrangement |
| Radical rearrangement | Bond migration, ring opening, or ring closure relocates the unpaired electron and forms a new radical intermediate | Cyclopropylcarbinyl radical ring opening |
| Pericyclic rearrangement | Bonds reorganize in a single concerted step through a cyclic transition state | Claisen and Cope rearrangements |
Common Named Rearrangements
In some reactions, rearrangement is only one step within a longer mechanism. Therefore, the overall product may contain different functional groups or even a different number of carbon atoms from the starting compound. [1,3,4]
| Named Rearrangement | Starting Material | Reagents or Conditions | Main Transformation | Main Product |
|---|---|---|---|---|
| Pinacol rearrangement | 1,2-Diol (vicinal diol) | Acidic conditions | Loss of water followed by a 1,2-migration and formation of a carbonyl group | Aldehyde or ketone |
| Beckmann rearrangement | Oxime | Acidic conditions or another activating reagent | The group positioned anti to the leaving group migrates from carbon to nitrogen | Amide; cyclic oximes form lactams |
| Hofmann rearrangement | Primary amide | Halogen and base | The remaining group migrates from the carbonyl carbon to nitrogen, and the original carbonyl carbon is ultimately lost as carbon dioxide | Primary amine containing one fewer carbon atom |
| Baeyer-Villiger oxidation | Ketone | Peroxy acid | A group attached to the carbonyl carbon migrates to oxygen, inserting an oxygen atom between the migrating group and the carbonyl carbon | Ester; cyclic ketones form lactones |
| Claisen rearrangement | Allyl vinyl ether | Heat | Concerted [3,3]-sigmatropic rearrangement involving simultaneous bond reorganization | γ,δ-unsaturated carbonyl compound |
| Cope rearrangement | 1,5-Diene | Heat | Concerted [3,3]-sigmatropic rearrangement involving reorganization of the carbon skeleton | Rearranged 1,5-diene |
Rearrangement reactions provide efficient pathways for converting one molecular framework into another, often enabling products that are difficult to obtain through direct reactions. They are therefore important for predicting unexpected products and explaining how molecular structure influences the course of organic reactions.
