Synthesis of 3,4-dihydro-2H-1,3-benzoxazines by condensation of 2-hydroxyaldehydes and primary amines: Application to the synthesis of hydroxy-substituted and deuterium-labeled compounds

We report the synthesis of several substituted 3,4-dihydro-2H-1,3-benzoxazines by simple ring closure of 2-hydroxybenzylamines with paraformaldehyde. The facile synthesis of the benzylamine precursors from commercially available salicylaldehyde derivatives affords a powerful general synthetic way to prepare a variety of substituted benzoxazines, avoiding the formation of undesirable oligomeric species, thus leading to a simple workup and improving the yield and purity of the final product. This straightforward method allows synthesis of hydroxy-substituted and deuterium-labeled 1,3-benzoxazines that are not attainable using other synthetic ways.