Theoretical evidence on O-N type smiles rearrangement mechanism:: a computational study on the intramolecular cyclization of N-methyl-2-(2-chloropyridin-3-yloxy)-acetamide anion

Smiles rearrangement (SR) falls under a broad category of organic synthesis for many important compounds. A complete understanding toward SR process appeals to the assistance of theoretical research. Herein, by performing quantum chemistry calculations, we give a theoretical evidence for the mechanism of a representative O-N type SR, the intramolecular cyclization of N-methyl-2-(2-chloropyridin-3-yloxy)acetamide anion. It is found that the SR to the ipso-position involves a two-step mechanism and is energetically more favorable than the direct nucleophilic attack by N atom on the ortho-position. The present result rationalizes well the experimentally observed ipso-SR product and provides a consistent picture of the O-N SR process. Copyright (c) 2008 John Wiley & Sons, Ltd.