Smiles rearrangement

What is Smiles rearrangement?

Henriques first reported the reaction in 1894, which was later explored by Smiles in 1930. The Smiles rearrangement is an intramolecular nucleophilic substitution that occurs on an aromatic system with an activating electron-withdrawing group present at the ortho– or para-position to the reaction center attached to a heteroatom.

Smiles rearrangement - general reaction scheme
Smiles rearrangement
  • W, W’ = NO2, SO2R, W =Cl
  • X = NH, O, S, SO, SO2, C(O)O, etc.
  • YH = OH, NHR, SH, CH2R, CONHR, etc. (see list of acronyms)

During this process, an aromatic ring migrates from the heteroatom binding to the reaction center to a more nucleophilic heteroatom, and hence it is commonly referred to as the Smiles rearrangement. Truce developed a comparable rearrangement via a carbon nucleophile, called the Truce-Smiles rearrangement. Moreover, a photochemical Smiles rearrangement initiated by photo irradiation was reported in 1970, and is known as the photo-Smiles rearrangement.

In the Smiles rearrangement, the two carbon atoms connecting to the two heteroatoms before and after the rearrangement are usually part of the aromatic system, but they may also be part of an aliphatic component. The leaving heteroatom or group can be O, S, SO, SO2, etc., and the attacking nucleophile can be the conjugate base of OH, NH2, CONH, SO2NH, etc., while the electron-withdrawing group is typically nitro or sulfonyl. However, it has been observed that a moderate electron-withdrawing group such as chloro can also activate the Smiles rearrangement. Steric hindrance due to a substituent at a particular position in the aromatic ring may facilitate the Smiles rearrangement as well. Even electron-donating solvents such as THF have a positive effect on increasing the rate of the Smiles rearrangement.

For example, the rearrangement of N-(2-hydroxyethyl)aryloxyacetamide to N-2-hydroxyethyl aniline can be accelerated by alkoxide, which is much faster than the rearrangement of corresponding simple primary amides or n-alkyl secondary amides under similar conditions.

The photo-Smiles rearrangement can also be accelerated by the addition of base, such as triethylamine, as demonstrated in the rearrangement of 2-(4-nitrophenoxy)-N-phenylethylamine to N-phenyl-N-(4-nitro-phenyl)-ethanolamine.

References

  • Henriques, R., Ber., 1894, 27, 2993
  • Warren, L. A. and Smiles, S., J. Chem. Soc., 1930, 956
  • Levy, A. A.; Rains, H. C. and Smiles, S., J. Chem. Soc., 1931, 3264
  • Evans, W. J. and Smiles, S., J. Chem. Soc., 1935, 181
  • Evans, W. J. and Smiles, S., J. Chem. Soc., 1936, 329
  • McClement, C. S. and Smiles, S., J. Chem. Soc., 1937, 1016
  • Matsui, K.; Maeno, N. and Suzuki, S., Tetrahedron Lett., 1970, 1467
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