1,2-rearrangement

A 1,2-rearrangement or 1,2-migration or 1,2-shift or Whitmore 1,2-shift cite journal | title = The common basis of molecular rearrangements | first = Frank C. | last = Whitmore | journal = J. Am. Chem. Soc. | date = 1932 | volume = 54 | issue = 8 | pages = 3274–3283 | doi = 10.1021/ja01347a037] 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.

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.

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 a 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 [Wieland, H. Chem. Ber. 1911, 44, 2550-2556.] was the conversion of bis(triphenylmethyl)peroxide 1 to the tetraphenylethane 2.

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 ["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] .

An example of a less common radical 1,2-shift can be found in the gas phase pyrolysis of certain polycyclic aromatic compounds cite journal | title = 1,2-Shifts of Hydrogen Atoms in Aryl Radicals | first = Michele A. | last = Brooks | coauthors = Lawrence T. Scott | journal = J. Am. Chem. Soc. | date = 1999 | volume = 121 | issue = 23 | pages = 5444–5449 | doi = 10.1021/ja984472d] . 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.

1,2 rearrangements

The following mechanisms involve a 1,2-rearrangement:
* Wagner-Meerwein rearrangement
* Pinacol rearrangement
* Hofmann rearrangement
* Curtius rearrangement
* Lossen rearrangement
* S_N1 reaction (generally)
* Halogen dance rearrangement
* 1,2-Wittig rearrangement
* Beckmann rearrangement
* Fritsch-Buttenberg-Wiechell rearrangement
* Criegee rearrangement
* Dowd-Beckwith ring expansion reaction
* Brook rearrangement
* Benzilic acid rearrangement
* Favorskii rearrangement
* Wolff rearrangement
* Stevens rearrangement
* Seyferth-Gilbert homologation
* Westphalen-Lettré 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