Parallel Synthesis of a Library of Benzoxazoles and Benzothiazoles Using Ligand-Accelerated Copper-Catalyzed Cyclizations of ortho-Halobenzanilides

Citations Over TimeTop 1% of 2006 papers

Abstract

A general method for the formation of benzoxazoles via a copper-catalyzed cyclization of ortho-haloanilides is reported. This approach complements the more commonly used strategies for benzoxazole formation which require 2-aminophenols as substrates. The reaction involves an intramolecular C-O cross-coupling of the ortho-haloanilides and is believed to proceed via an oxidative insertion/reductive elimination pathway through a Cu(I)/Cu(III) manifold. The reaction is also applicable to the formation of benzothiazoles. A variety of ligands including 1,10-phenanthroline and N,N'-dimethylethylenediamine were shown to provide ligand acceleration/stabilization in the reaction. Optimal conditions for cyclization used a catalyst combination of CuI and 1,10-phenanthroline (10 mol %). The method was amenable to a parallel-synthesis approach, as demonstrated by the synthesis of a library of benzoxazoles and benzothiazoles substituted at various positions in the ring. Most examples utilized the cyclization of ortho-bromoanilides, but ortho-iodoanilides and ortho-chloroanilides also undergo a reaction under these conditions. The rate of reaction of the ortho-haloanilides follows the order I > Br > Cl, consistent with oxidative addition being the rate-determining step.

Related Papers

• → A study on the genotoxic activities of some new benzoxazoles(2007)48 cited
• → A new method of synthesis of some 2‐aryl and 2‐heterocyclic benzimidazole, benzoxazole and benzothiazole derivatives(1979)38 cited
• → Reaction of the 2-(bromodifluoromethyl)benzoxazole with tetrakis(dimethylamino)ethylene (TDAE) in the presence of aldehydes. A convenient synthesis of 2-(difluoromethyl)benzoxazole alcohols(1997)28 cited
• Design, synthesis and screening of some novel benzoxazole based 1,3,4-oxadiazoles as potential antimicrobial agents(2013)
• → Cyanoacetylenes in a reaction with benzoxazole-2-thione and benzoxazol-2-one(1990)1 cited