Regioselective syntheses of 2- and 4-formylpyrido[2,1-b]benzoxazoles

J Org Chem. 2009 May 1;74(9):3286-92. doi: 10.1021/jo900267c.


o-Acetaminophenols (2) reacted with Vilsmeier reagent under Meth-Cohn conditions to yield 2-formylpyrido[2,1-b]benzoxazoles (5) unexpectedly besides the known compounds 2-(benzoxazol-2'-yl)-3-dimethylaminoacroleins (4). Refluxing 4 in acetic anhydride gave 4-formylpyrido[2,1-b]benzoxazoles (6), an isomer of 5. Both 5a and 6a were structurally characterized by X-ray crystallography. A mechanism for the formation of 5 involving sequential chlorination, dimerization, intramolecular elimination of HCl to form the oxazole ring, formylation twice, and regioselective intramolecular nucleophilic cyclization to construct the pyridone ring is proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoxazoles / chemical synthesis*
  • Benzoxazoles / chemistry
  • Stereoisomerism
  • Substrate Specificity


  • Benzoxazoles