Copper-catalyzed synthesis of benzoxazoles via tandem cyclization of 2-halophenols with amidines

Abstract

This work reports a simple, efficient and alternative synthetic route for the preparation of benzoxazoles via tandem cyclization of 2-halophenols with amidines. The developed methodology is free from ligands and uses inexpensive and easily available CuCl as a catalyst. This protocol avoids the use of any oxidant or inorganic acids. Various benzoxazole derivatives were synthesized in good to excellent yields. To the best of our knowledge, this is the first time that the synthesis of benzoxazoles from 2-halophenols with both aromatic and aliphatic amidines is reported. Owing to the simplicity of this protocol, the preparation of benzoxazoles could be achieved at a gram scale level.

Recent advances in the tandem copper-catalyzed Ullmann–GoldbergN-arylation–cyclization strategies

“…Organic & Biomolecular Chemistry (Scheme 24). 39 It is considered as the first report for the synthesis of benzoxazole via copper-catalyzed coupling between 2-halophenols and amidines. 2.3.3.…”

Consecutive Oxidation/Condensation/Cyclization/Aromatization Sequences Catalyzed by Nanostructured Iron(III)‐Porphyrin Complex towards Benzoxazole Derivatives

“…[17][18][19] In this regard, numerous synthetic protocols for 2-substituted benzoxazole derivatives have been described in the literature (Figure 2). [20][21][22][23][24][25][26][27][28][29][30][31][32] While the strategies as mentioned above enriched approaches to 2-substituted benzoxazole derivatives, their applicability is often compromised by the use of expensive metals, utilization of harsh reaction conditions, high catalyst loading, and use of volatile and toxic organic solvents.…”

“…Furthermore, there is a remarkable interest to develop new strategies for the efficient and more applicable synthesis of 2‐substituted benzoxazole derivatives in recent years . In this regard, numerous synthetic protocols for 2‐substituted benzoxazole derivatives have been described in the literature (Figure ) …”

CuNiFe a Magnetic Nano‐Catalyst: an Efficient Catalyst for the Selective Synthesis of Benzoxazoles

“…Nitrogen containing heterocycles such as benzoxazole and its derivatives are important building blocks for the synthesis of pharmaceutical products, agrochemical compounds and functional materials . Traditionally, benzoxazoles have been synthesized by (i) condensation of 2‐aminophenols with carboxylic acids, aldehydes, benzyl alcohols, and benzyl amines,, (ii) transition metal‐catalyzed intramolecular cyclization of 2‐haloanilides or their analogs,, (iii) tandem cyclization of 2‐halophenol with amidines, (iv) intermolecular cross‐coupling of 1,2‐dihaloarenes with primary amides …”