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

1,3-Rearrangements

1,3-rearrangements take place over 3 carbon atoms. Examples:

• the Fries rearrangement
• a 1,3-alkyl shift of verbenone to chrysanthenone

References

1. Whitmore, Frank C. (1932). "The common basis of molecular rearrangements". J. Am. Chem. Soc. 54 (8): 3274–3283. doi:10.1021/ja01347a037.
2. Über Triphenylmethyl-peroxyd. Ein Beitrag zur Chemie der freien Radikale Wieland, H. Chem. Ber. 1911, 44, 2550–2556. doi:10.1002/cber.19110440380
3. Isomerization of Triphenylmethoxyl and 1,1-Diphenylethoxyl Radicals. Revised Assignment of the Electron-Spin Resonance Spectra of Purported Intermediates Formed during the Ceric Ammonium Nitrate Mediated Photooxidation of Aryl Carbinols K. U. Ingold, Manuel Smeu, and Gino A. DiLabio J. Org. Chem.; 2006; 71(26) pp 9906–9908; (Note) doi:10.1021/jo061898z
4. Brooks, Michele A.; Lawrence T. Scott (1999). "1,2-Shifts of Hydrogen Atoms in Aryl Radicals". J. Am. Chem. Soc. 121 (23): 5444–5449. doi:10.1021/ja984472d.