1,2-rearrangement

A 1,2-rearrangement or 1,2-migration or 1,2-shift or Whitmore 1,2-shift^[1] is an organic reaction where a substituent moves from one atom to another atom in a chemical compound. In a 1,2 shift the movement involves two adjacent atoms but moves over larger distances are possible. In the example below the substituent R moves from carbon atom C² to C³.

1,2-shift

The rearrangement is intramolecular and the starting compound and reaction product are structural isomers. The 1,2-rearrangement belongs to a broad class of chemical reactions called rearrangement reactions.

A rearrangement involving a hydrogen atom is called a 1,2-hydride shift. If the substituent being rearranged is an alkyl group, it is named according to the alkyl group's anion: i.e. 1,2-methanide shift, 1,2-ethanide shift, etc.

Reaction mechanism

A 1,2-rearrangement is often initialised by the formation of a reactive intermediate such as:

• a carbocation by heterolysis in a nucleophilic rearrangement or anionotropic rearrangement
• a carbanion in an electrophilic rearrangement or cationotropic rearrangement
• a free radical by homolysis
• a nitrene.

The driving force for the actual migration of a substituent in step two of the rearrangement is the formation of a more stable intermediate. For instance a tertiary carbocation is more stable than a secondary carbocation and therefore the S_N1 reaction of neopentyl bromide with ethanol yields tert-pentyl ethyl ether.

Carbocation rearrangements are more common than the carbanion or radical counterparts. This observation can be explained on the basis of Hückel's rule. A cyclic carbocationic transition state is aromatic and stabilized because it holds 2 electrons. In an anionic transition state on the other hand 4 electrons are present thus antiaromatic and destabilized. A radical transition state is neither stabilized or destabilized.

The most important carbocation 1,2-shift is the Wagner–Meerwein rearrangement. A carbanionic 1,2-shift is involved in the benzilic acid rearrangement.

Radical 1,2-rearrangements

The first radical 1,2-rearrangement reported by Heinrich Otto Wieland in 1911^[2] was the conversion of bis(triphenylmethyl)peroxide 1 to the tetraphenylethane 2.

Radical 1,2-rearrangement

The reaction proceeds through the triphenylmethoxyl radical A, a rearrangement to diphenylphenoxymethyl C and its dimerization. It is unclear to this day whether in this rearrangement the cyclohexadienyl radical intermediate B is a transition state or a reactive intermediate as it (or any other such species) has thus far eluded detection by ESR spectroscopy.^[3]

An example of a less common radical 1,2-shift can be found in the gas phase pyrolysis of certain polycyclic aromatic compounds.^[4] The energy required in an aryl radical for the 1,2-shift can be high (up to 60 kcal/mol or 250 kJ/mol) but much less than that required for a proton abstraction to an aryne (82 kcal/mol or 340 kJ/mol). In alkene radicals proton abstraction to an alkyne is preferred.

Aryl radical 1,2-shift in a helicene

1,2-Rearrangements

The following mechanisms involve a 1,2-rearrangement:

• 1,2-Wittig rearrangement
• Alpha-ketol rearrangement
• Beckmann rearrangement
• Benzilic acid rearrangement
• Brook rearrangement
• Criegee rearrangement
• Curtius rearrangement
• Dowd–Beckwith ring expansion reaction
• Favorskii rearrangement
• Friedel–Crafts reaction
• Fritsch–Buttenberg–Wiechell rearrangement
• Halogen dance rearrangement
• Hofmann rearrangement
• Lossen rearrangement
• Pinacol rearrangement
• Seyferth–Gilbert homologation
• S_N1 reaction (generally)
• Stevens rearrangement
• Stieglitz rearrangement
• Wagner–Meerwein rearrangement
• Westphalen–Lettré rearrangement
• Wolff rearrangement