Acid Catalyzed Direct-Amidation–Dehydrocyclization of 2-Hydroxy-acetophenones to Benzoxazoles by a One-Pot Sustainable Synthesis Elia Rancan • Fabio Arico ` • Giuseppe Quartarone • Lucio Ronchin • Andrea Vavasori Received: 3 September 2014 / Accepted: 14 December 2014 Ó Springer Science+Business Media New York 2014 Abstract A series of 2-methyl-benzoxazoles have been synthesized starting from 2-hydroxy-acetophenones via a one-pot three steps reaction. Hydroxylamonium salt has been used as amidation agent. The reaction occurs with different anions, but the best results is achieved with hy- droxylamonium hydrchloride. Despite the number of con- secutive stages, the reaction is highly selective. Mild reaction conditions and various solvents can be used, but trifluoroacetic acid is the preferred. Almost, complete recovery of the trifluoroacetic acid can be achieved by vacuum distillation. The role of trifluoroacetic acid, as well as, of the hydroxylamonium salt suggests a cooperative effect leading to high selective formation of 2-methyl- benzoxazoles. Graphical Abstract One-pot TFA catalyzed synthesis of benzoxazoles starting from 2-hydroxyacetophenones. Keywords Benzoxazoles Á Direct-amidation– dehydrocyclization Á Trifluoroacetic acid Á Acid catalysis 1 Introduction In the field of fine chemicals, the development of new and efficient synthetic strategies with higher atom economy has been continuously pursued by industrial researchers as it represents a great chance to develop sustainable processes from both economical and environmental point of view [1]. The recent trends for greener strategy are mainly based on converting multi stages synthesis in one-pot process by reducing plant operations, as well as, formation of One-pot TFA catalyzed synthesis of benzoxazoles starting from 2-hydroxyacetophenones CH 3 O OH N O CH 3 TFA - H 2 O NH 2 O H + HCl . Electronic supplementary material The online version of this article (doi:10.1007/s10562-014-1466-3) contains supplementary material, which is available to authorized users. E. Rancan Á G. Quartarone Á L. Ronchin (&) Á A. Vavasori Department of Molecular Science and Nanosystems, Ca’ Foscari University, 2137 Dorsoduro, 30123 Venice, Italy e-mail: ronchin@unive.it E. Rancan Á F. Arico ` Á G. Quartarone Á L. Ronchin Á A. Vavasori Green Chemistry Group, 2137 Dorsoduro, 30123 Venice, Italy F. Arico ` Department of Environmental Science, Informatics and Statistics, Ca’ Foscari University, 2137 Dorsoduro, 30123 Venice, Italy 123 Catal Lett DOI 10.1007/s10562-014-1466-3