Copper-Catalyzed Intramolecular Cyclization of 2-Haloacetanilines to Benzo[d]oxazoles

Significance

A general synthetic protocol for the copper-catalyzed O-arylation of ortho-haloanilides to benzo[d]oxazoles is reported. Various copper sources as well as Cu/ligand combinations were tested but CuCl/TMEDA or Cu(OTf)₂/TMEDA combinations proved to afford the best yields. Although the yields are only moderate at best, the reported procedure has advantages in that a) inexpensive and readily available aryl chlorides can be used and b) the reaction medium is water. Both points render the procedure highly attractive from economic and ecological points of view. Although various carboxamides (especially heterocyclic, R² = 3-furyl, thiophen-2-yl) were successfully applied in the reaction, the substitution in the halo­anilide was insufficiently studied.